Ileoscopy: Technique, Diagnosis, and Clinical Applications

Ileoscopy

Antonello Trecca Editor

Ileoscopy Technique, Diagnosis, and Clinical Applications Foreword by Shin-ei Kudo

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Editor Antonello Trecca Endoscopic and Operative Gastroenterology Units USI Group Rome Italy e-mail: [email protected]

ISBN 978-88-470-2344-4 DOI 10.1007/978-88-470-2345-1

e-ISBN 978-88-470-2345-1

Springer Milan Heidelberg Dordrecht London New York Library of Congress Control Number: 2011941715 Ó Springer-Verlag Italia 2012 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the Italian Copyright Law in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the Italian Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudio Calamar S.L. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

To my father, Pasquale Trecca

Foreword

It is a great pleasure to see the publication of IIeoscopy, edited by Dr. Antonello Trecca. Dr. Trecca studied endoscopic diagnosis and treatment of early cancers of the gastrointestinal tract at the National Cancer Center Hospital, Tokyo, Japan. He is an expert in magnifying endoscopy, including pit pattern diagnosis, and also has an excellent understanding of the importance of depressed type early colorectal cancers. Colonoscopy (from diagnostic to technical aspects, including magnifying endoscopy, insertion technique, and endoscopic treatment) is an essential tool in the gastrointestinal field. With the emergence of the magnifying colonoscope, pit pattern analysis enables a diagnosis with a close relation to histologic diagnosis. Today, there are plenty of textbooks of colonoscopy, but fewer of terminal ileoscopy. The importance of terminal ileoscopy during routine colonoscopy, however, should not be underestimated. We can diagnose many ileal diseases with terminal ileoscopy without using capsule endoscopy or balloon enteroscopy. This book is dedicated to the role of exploration of the terminal ileum in lower gastrointestinal endoscopy. It covers both technical aspects and the modern diagnosis and treatment of small intestinal diseases in a very accessible format. It will be an indispensable guide not only for colonoscopists but also for gastroenterologists and surgeons. I hope that this book will find the wide readership it doubtlessly deserves. Prof. Shin-ei Kudo Digestive Disease Center Showa University Northern Yokohama Hospital Yokohama Japan

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Preface

The challenge for the authors of a medical/scientific monograph is to communicate both their passionate interest in and their dedication to the subject matter, whether a disease, a new technique, an original therapeutic approach, or the most recent trends in clinical and experimental research. Of equal importance is to consider the scope of the audience, which may include students, interns, and residents but also highly experienced professionals. We have kept these goals in mind in our exploration of the difficult subject of digestive endoscopy, specifically, of the terminal ileum, and the most important issues related to the use of this technique in various disease settings. Each chapter consists of a thorough discussion of a particular topic, which is illustrated by a large number of detailed images. In the field of modern gastroenterology, digestive endoscopy continues to be the focus of enormous interest because of the many achievements over the last several decades: from the introduction of capsule endoscopy to the development of enteroscopy. These imaging capabilities have greatly expanded our knowledge of intestinal diseases while opening up new frontiers in their more accurate treatment. Exploration of the terminal ileum during total colonoscopy has gained much greater acceptance within the profession based on the diagnostic accuracy of terminal ileoscopy with respect to ileocecal pathologies, including neoplasias of the cecal region. In addition, terminal ileoscopy documents the completeness of colonoscopy and points the way to the optimal procedure for further study of the intestine. This capability is such that we provocatively refer to ileoscopy as the fast track to the diagnosis of gut diseases. The multidisciplinary approach taken by the authors of this volume to the accurate study of the ileocecum is highlighted by the contributions of experts in radiology and surgery, providing a closer look at several intestinal diseases. Particular emphasis has been placed on endoscopic imaging of the different disease stages and on analyzing the results obtained with the new techniques in terms of their ability to enhance diagnostic accuracy. We would like to thank all the authors who actively participated in realizing this book, for their clinical efforts and scientific contributions. To our readers: we hope that we have been able to contribute to your professional development and to have inspired in you the same passionate interest that has resulted in this book. Rome, September 2011

Antonello Trecca

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Acknowledgments

The editor would like to thank Raffaele Gurrieri, for the illustrations drawn for Chap. 1 with passion and competence, and Astrid Gurrieri, for her unflagging contribution to the book.

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Contents

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Terminal Ileoscopy: Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . Antonello Trecca, Giuseppe Cerno, Emilio Gentile Warschauer, Gabriele Marinozzi, and Fabio Gaj

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The Importance of Complete Colonoscopy and Exploration of the Cecal Region . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kuangi Fu, Takahiro Fujii, Takahisa Matsuda, and Yutaka Saito

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What are the Correct Indications for Ileoscopy? . . . . . . . . . . . . . . Antonello Trecca, Fabio Gaj, Stefano Serafini, Gabriele Marinozzi, and Marco Silano

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Contribution of New Technologies to Endoscopic Imaging . . . . . . . Giuseppe Galloro, Luca Magno, Simona Ruggiero, Ferdinando Fusco, and Tiziana Rappa

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Ileoscopy in Coeliac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Marco Silano, Emilio Gentile Warschauer, Gabriele Marinozzi, Giuseppe Cerno, and Antonello Trecca

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The Role of Ileoscopy in Inflammatory Bowel Disease . . . . . . . . . . Bjorn Rembacken and Mohammed Thoufeeq

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Ileoscopy in the Diagnosis of Infectious Diseases . . . . . . . . . . . . . . Roberto Lorenzetti, Angelo Mario Zullo, and Cesare Hassan

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Results of Ileoscopy in Pediatric Patients. . . . . . . . . . . . . . . . . . . . Paola De Angelis, Erminia Romeo, Filippo Torroni, and Luigi Dall’Oglio

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The Role of Histology in Small Bowel Diseases . . . . . . . . . . . . . . . Vincenzo Villanacci and Gabrio Bassotti

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Radiological Diagnosis of Small-Bowel Diseases . . . . . . . . . . . . . . . Laura Maria Minordi, Amorino Vecchioli, Luigi Larosa, and Lorenzo Bonomo

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Contents

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Capsule Endoscopy: The Answer to a Challenge . . . . . . . . . . . . . . Emanuele Rondonotti and Roberto de Franchis

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Double-Balloon Enteroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alessandro Mussetto and Tino Casetti

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Single-Balloon Enteroscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mauro Manno, Raffaele Manta, and Rita Conigliaro

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Spiral Enteroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mauro Manno, Raffaele Manta, and Rita Conigliaro

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Surgery for Small-Bowel Disease. . . . . . . . . . . . . . . . . . . . . . . . . . Ugo Grossi, Andrea Mazzari, Pasquina MC Tomaiuolo, Giuseppe Brisinda, and Antonio Crucitti

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Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Contributors

Gabrio Bassotti Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy Lorenzo Bonomo Department of Bio-Imaging and Radiological Sciences, Catholic University (UCSC), Radiology Institute, Rome, Italy Giuseppe Brisinda General Surgery, Catholic University of Rome, Rome, Italy Tino Casetti Department of Gastroenterology, Santa Maria delle Croci Hospital, Ravenna, Italy Giuseppe Cerno Department of Pathology, USI Group, Rome, Italy Endoscopic and Operative Units, Department of Pathology, USI Group, Rome, Italy Histopathology Endoscopic and Operative Gastroenterological Units, USI Group, Rome, Italy Rita Conigliaro Gastroenterology and Digestive Endoscopy Unit, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy Antonio Crucitti General Surgery, Catholic University of Rome, Rome, Italy Luigi Dall’Oglio Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico Bambino Gesu`, IRCCS, Rome, Italy Paola De Angelis Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico Bambino Gesu`, IRCCS, Rome, Italy Roberto de Franchis Gastroenterology Unit, L. Sacco Hospital, University of Milan, Milan, Italy Kuangi Fu Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan Takahiro Fujii TF clinic, Tokyo, Japan Ferdinando Fusco Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy Fabio Gaj Department of General Surgery, University of Rome ‘‘La Sapienza’’, Rome, Italy

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Giuseppe Galloro Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy Ugo Grossi General Surgery, Catholic University of Rome, Rome, Italy Cesare Hassan Gastroenterology Department, Nuovo Regina Margherita Hospital, Rome, Italy Roberto Lorenzetti Gastroenterology Department, Nuovo Regina Margherita Hospital, Rome, Italy Luigi Larosa Department of Bio-Imaging and Radiological Sciences, Catholic University (UCSC), Radiology Institute, Rome, Italy Luca Magno Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy Mauro Manno Gastroenterology and Digestive Endoscopy Unit, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy Raffaele Manta Gastroenterology and Digestive Endoscopy Unit, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy Gabriele Marinozzi Department of Operative Endoscopy, Saint Mary Hospital, Terni, Italy Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy Takahisa Matsuda Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan Andrea Mazzari General Surgery, Catholic University of Rome, Rome, Italy Laura Maria Minordi Department of Bio-Imaging and Radiological Sciences, Catholic University (UCSC), Radiology Institute, Rome, Italy Alessandro Mussetto Department of Gastroenterology, Santa Maria delle Croci Hospital, Ravenna, Italy Tiziana Rappa Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy Bjorn Rembacken Department of Endoscopy, General Infirmary Hospital, Leeds, UK Mohammed Thoufeeq Department of Endoscopy, General Infirmary Hospital, Leeds, UK Erminia Romeo Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico Bambino Gesu`, IRCCS, Rome, Italy Emanuele Rondonotti Gastroenterology Unit, Ospedale Valduce, Como, Italy

Contributors

Contributors

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Simona Ruggiero Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy Yutaka Saito Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan Stefano Serafini Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy Marco Silano Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanita`, Rome, Italy Pasquina M. C. Tomaiuolo General Surgery, Catholic University of Rome, Rome, Italy Filippo Torroni Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico Bambino Gesu`, IRCCS, Rome, Italy Antonello Trecca Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy Amorino Vecchioli Department of Bio-Imaging and Radiological Sciences, Catholic University (UCSC), Radiology Institute, Rome, Italy Vincenzo Villanacci Department of Pathology, Spedali Civili, University of Brescia, Brescia, Italy Emilio Gentile Warschauer Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy Angelo Mario Zullo Gastroenterology Department, Nuovo Regina Margherita Hospital, Rome, Italy

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Terminal Ileoscopy: Technique Antonello Trecca, Giuseppe Cerno, Emilio Gentile Warschauer, Gabriele Marinozzi, and Fabio Gaj

1.1

Introduction

The basic requirement for the intubation of the terminal ileum is knowledge of the anatomy of the ileocecal region and of the main appearances of the ileocecal valve (ICV), accompanied by an appropriate level of technical skill in performing colonoscopy.

1.2

Anatomy of the Ileocecal Region

The cecum is the first part of the large intestine and it occupies the right iliac fossa. Guarding the opening of the ileum (the terminal portion of the small intestine) into the cecum is the ICV [1]. The cecum is located below a transversal plane running along the ileocecalcolic sphincter (Fig. 1.1). It forms a rounded sac between 6 and 10 cm long, with an internal diameter of 5–6 cm and a capacity of 200–300 ml. Three teniae coli enfold this region, defined as anterior, posterolateral, and posteromedial on the basis of their position. The posteromedial tenia coli forms the entrance into the terminal ileum. The longitudinal axis of the cecum and that of the right colon together create an obtuse angle that opens forward and medially. The cecum is lodged together with the terminal ileum and is completely covered by the peritoneal wall. It is separated from the ileum by the ICV (also

A. Trecca (&) Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy e-mail: [email protected]

called the Bauhin valve), which is composed of two segments—an upper lip and a lower lip—that are formed by intrusion of the circular muscle layer of the ileum into the lumen of the large intestine. A narrow membranous ridge continues at the ends of the aperture medially and laterally, where the lips meet, giving rise to the frenula of the valve. The circular muscle fibers of the ileum and those of the cecum combine to form the circular sphincter muscle of the ICV, whose role is to limit the rate of food passage into the cecum and to prevent material from returning to the small intestine. The valve acts through the contraction of the frenula in response to overstretching of the cecum, but it has minimal sphincteric action, a fact that explains the common observation of barium reflux into the terminal ileum during a barium enema examination. Intestinal occlusion results in a persistent contraction of the ICV, with consequent rupture of the cecum (called diastasis rupture), or its relaxation, with continuous reflux of the feces and the overstretching of the terminal ileum. The ileum comprises three-fifths of the small intestine, although there is no absolute point at which the jejunum ends and the ileum begins. In broad terms, the jejunum occupies the upper left part of the abdomen below the subcostal plane (that is, at the level of the 10th rib), while the ileum is located in the lower right part. It has numerous convolutions and is attached to the posterior abdominal wall by the mesentery, an extensive fold of serous-secreting membrane that is missing at the level of the terminal ileum, thereby determining its complete mobility in the abdominal cavity. The arterial blood supply to the large intestine comes from branches of the superior and inferior mesenteric arteries (both of which are branches of the

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_1, Ó Springer-Verlag Italia 2012

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abdominal aorta) and the hypogastric branch of the internal iliac artery (which supplies blood to the pelvic walls and viscera, the genital organs, the buttocks, and the inside of the thighs). The vessels form a continuous row of arcades from which vessels arise to enter the large intestine. Venous blood is drained from the colon via branches that form arcades, analogous to those of the arteries. The blood from these veins eventually drains into the superior and inferior mesenteric veins, which ultimately join with the splenic vein to form the portal vein. The ileocecal region has both parasympathetic and sympathetic innervation. The vagus nerve provides parasympathetic innervation. Sympathetic innervation is provided by branches of the superior mesenteric plexus, a nerve network underneath the solar plexus that follows the blood vessels into the small intestine and finally terminates in the Auerbach plexus, which is located between the circular and longitudinal muscle coats, and in the Meissner plexus, which is located in the submucosa. Numerous fibrils, both adrenergic (sympathetic) and cholinergic (parasympathetic), connect these two plexuses.

71 patients (78%) and triangular in 20 (22%). At colonoscopy, all patients with a normal valve at double-contrast barium enema examination had a normal valve, whereas the two patients with a valve suspicious for tumor at barium enema examination had neoplasms (one carcinoma and one villous adenoma). In a comparative study between doublecontrast barium enema and ileoscopy, a macroscopically normal appearance of the ICV was detected in 30 patients. Among these patients, 60% were diagnosed with mild, 26.7% with moderate, and 13.3% with severe endoscopic ileal inflammation. The ICV was affected by Crohn’s disease (CD) in 70 patients, in whom significantly more severe ileal inflammation (p \ 0.005) was detected than in patients with a normal-looking ICV. The authors of that study concluded that ileal exploration should be attempted in every patient suspected of having CD, because, although the appearance of the ICV correlates with the severity of ileal inflammation, a normal-looking ICV does not correspond to normal ileal mucosa in many cases [2]. At endoscopy, the ICV may be classified as labial, papillary, or lipomatous based on its morphologic appearance [3, 4]. The labial type has a slit-like opening, the papillary type is dome shaped, and the lipomatous type has a substantial deposit of fat within its lips. However, most non-lipomatous valves will demonstrate streaks of fat within the valve lips. Each ICV subtype may vary in appearance depending on whether the patient is prone or supine or whether the valve is open rather than closed. Another endoscopic classification defines the ICV with the cecum moderately inflated: thin lipped, when the fold has no bulge; single or double bulging, when one or two prominent bulges of the fold are present; and volcanic, when the fold is exuberant and the orifice is visible. Of these, the thin lipped morphology is the most difficult to intubate (Fig. 1.2).

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1.4

Fig. 1.1 The anatomy of the ileocecal region

Ileocecal Valve Appearances

The ICV may show a spectrum of normal findings at double-contrast barium enema, appearing as a round, ovoid, or triangular structure with a maximum height of nearly 4 cm. The valve may be large, asymmetric, or smoothly lobulated. In a series of 106 patients, the ICV was visible in 91 (86%), being round or ovoid in

Ileoscopy: Technique

The correct positioning of the colonoscope in the ileocecal region is an essential step in the intubation of the ICV. Straightening the colonoscope in the left but also in the transverse colon guarantees its good maneuverability, allowing easy passage into the ileum (Fig. 1.3). Once the ICV is reached, its position in the

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Fig. 1.2 The ileocecal valve morphology. a Thin-lipped or labial. b Single-bulge or papillary. c Double-bulge or papillary. d Volcanic or lipomatous

Fig. 1.3 The correct position of the colonoscope for ileoscopy

intestinal lumen must be considered as well as the decubitus of the patient. With the patient supine and the ICV at the 9 o’clock position, downward deflection is recommended to stretch the lower lip, and anti-clockwise torque with the left hand gently accompanying the scope toward the left (Fig. 1.4). When the patient is in left lateral decubitus, the ICV appears in the 6- or 7-o’clock position and passage into the ileum can be achieved with the same maneuvers. Sometimes the ICV is positioned in the 12- to 1-o’clock position and a combination of upward deflection and clockwise torque (opposite from that described above) may be necessary. In case of a thin-lipped valve, which, as noted above, is the most difficult one to intubate, due to difficult visualization of the upper and lower lips, a retroversion of the tip of the scope in the cecal region can help to identify the valve. In this case, the scope is withdrawn and the tip is straightened, before the instrument is advanced into the ileum (Fig. 1.5). Once the endoscope has entered in the ileal lumen, the ileum must

Fig. 1.4 a, d, g Manipulation of the scope using the left hand during ileal intubation. b, e, h Position of the patient and manipulation of the scope using the right hand during ileal intubation. c, f, i Position of the colonoscope within the intestinal lumen during the different steps of the procedure

be insufflated with a good amount of air in order to position the scope, avoiding its retreat into the cecum [5, 6]. The use of hyoscine-n-butyl bromide reduces bowel motion and may also facilitate ileal intubation [7]. Exploration of the last 10–15 cm of the ileum is always possible, with advancement of the scope facilitated by abdominal compression. The reported incidence of complications during ileoscopy is essentially null, both in unsedated and sedated patients, especially if the use of biopsy forceps to intubate a difficult valve or insufflating large amounts of air in the ileocecal region is avoided [8–11]. Once the scope is in the ileal lumen, its withdrawal, accompanied by a moderate insufflation of air,

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A. Trecca et al. Table 1.1 Magnified ileoscopy technique Step 1: Washing the mucosa with a mucolytic agent Step 2: Dye-spraying with a solution of 5–8 ml of indigo carmine 0.4% Step 3: Magnifying view Step 4: Endoscopic evaluation

Table 1.2 Virtual magnified ileoscopy technique Step 1: Washing the mucosa with a mucolytic agent Step 2: Filling the lumen with saline Step 3: Activating virtual chromoendoscopy Step 4: Magnifying view Step 5: Endoscopic evaluation

enables an accurate evaluation of the endoscopic appearance of the terminal ileum, searching for the presence of hyperemia, aphthoid lesions, erosions, or ulcers. The standard view cannot describe the morphology of the general villous architecture, which instead can be outlined only after the injection of 10–15 ml of saline through the biopsy channel, as confirmed in a prospective, observational study on 216 consecutive completed colonoscopies in which the images of the terminal ileum were significantly more likely than cecal images to be considered convincing in order to verify the extent of colonoscopy (p \ 0.0001 for all reviewers). The instillation of sterile water in the intestinal lumen was considered by the authors as a prerequisite to obtain accurate photodocumentation [12].

the study of the terminal ileum (magnified ileoscopy, Table 1.1) [13]. The steps of the procedure are similar to those followed for the colon, including washing the mucosa with mucolytic agents in order to enhance the villous profile and then spraying the lumen with dye (5–8 ml of indigo carmine 0.4%). The dye, with its capacity to pool in any minimal depression, further enhances the villous profile, highlighting the presence of lymphoid follicles and the subtotal or total atrophy of the terminal ileum. The endoscopist, after an accurate evaluation of the sprayed mucosa, can scan the region, identifying the pathological area for study and performing a target biopsy. Magnified ileoscopy allows a much more accurate study of the terminal ileum. It can be used to determine the presence of even subtle changes of the mucosa, such as hyperemia, and of small aphthoid or erosive lesions, which can be missed at conventional view. It also reveals the villous morphology, including the size of the villi, and potential atrophy of the terminal ileum, neither of which are seen on conventional endoscopy. Caution must be exerted by the endoscopist to avoid spraying too much dye, because it can alter the visualization of the mucosa with backflow to the ileocecal region, thus compromising the inspection of this area.

1.4.1

1.4.2

Fig. 1.5 a, d, g Manipulation of the scope using the left hand during ileal intubation. b, e, h Position of the patient and manipulation of the scope using the right hand during ileal intubation. c, f, i Position of the colonoscope within the intestinal lumen during the different steps of the procedure

Magnified Ileoscopy

The important clinical results obtained with magnifying endoscopy for the detection and definition of early colorectal cancer led us to reproduce this technique for

Virtual Chromoendoscopy

Virtual chromoendoscopy, called narrow-band imaging (NBI), represents another aid to the endoscopist. The NBI system makes use of optical filters within the

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Fig. 1.6 Normal villous morphology. a Conventional view of the terminal ileum with normal finding. b, c Virtual magnified ileoscopy shows the normal villous pattern, with evidence of a single lymphatic follicle. d–f Histology of the normal villous morphology

Fig. 1.7 Normal villous morphology with evidence of multiple lymphatic follicles. a Conventional view of the terminal ileum, showing diffuse hyperemia. b, c Virtual magnified ileoscopy with normal villous pattern and multiple lymphatic follicles. d, e Histology shows non-specific ileitis

light source of a videoendoscope, selecting light in short and limited wavelengths within the hemoglobin absorption band. The most recent development is computed virtual chromoendoscopy imaging, invented by Yoichi Miyake (Faculty of Engineering, Chiba University, Chiba, Japan) and introduced by Fujinon as Fujinon Intelligent Color Enhancement (FICE). FICE is based on the same physical principle as NBI, but due to a new computed spectral estimation technology it is not dependent on optical filters. The FICE technology takes an ordinary endoscopic image from the video processor and arithmetically processes the reflected photons to reconstitute virtual images by increasing the relative intensity of narrowed blue (B) light to a maximum and decreasing narrowed red (R) and green (G) light to a minimum. FICE successfully realizes enhancements and real-time observations of mucosal and microvascular patterns [14–17]. By cutting off the

longer wavelengths, FICE improves the contrast of the capillary patterns and enhances the structure of the mucosal surface. Virtual chromoendoscopy thus provides dyeless contrast and constitutes an easyto-use diagnostic technology. The digital processing system allows switching between conventional images and FICE-NBI images by a simple push of a button on the endoscope [18, 19] (virtual magnified ileoscopy; Table 1.2, Figs. 1.6 and 1.7).

1.5

Conclusions

Terminal ileoscopy during colonoscopy is of pivotal importance for the detection and definition of ileal pathology. The endoscopist should be familiar with the ileocecal anatomy and with the different possible morphologies of the ICV. Following brief but indispensable training, proficiency in ileal intubation can

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be achieved after 50 procedures. The principles of the technique should be kept in mind by both the trainee and the expert in order to simplify intubation of the last 20 cm of the ileum. A broad spectrum of ileal diseases can be excluded during investigation of this region, which has been significantly improved by the contribution of recent technological advances, mainly magnified ileoscopy.

References 1. Lambertini G (1977) Anatomia umana. Piccin, Padova 2. Silva AC, Beaty SD, Hara AK, Fletcher JG, Fidler JL, Menias CO, Johnson CD (2007) Spectrum of normal and abnormal CT appearances of the ileocecal valve and cecum with endoscopic and surgical correlation. Radiographics 27:1039–1054 3. Cotton P, Williams CB (1996) Practical gastrointestinal endoscopy. Blackwell Science, Oxford, pp 54–58 4. Iacopini G, Frontespezi S, Vitale MA, Villotti G, Bella A, D’Alba L, De Cesare A, Iacopini F (2006) Routine ileoscopy at colonoscopy: a prospective evaluation of learning curve and skill-keeping line. Gastrointest Endosc 63:250–256 5. Chen M, Khanduja KS (1997) Intubation of the ileocecal valve made easy. Dis Colon Rectum 40:494–496 6. Gabrielsson N, Granqvist S (1977) A new technique for insertion of the colonoscope through the ileocecal valve. Endoscopy 9:38–41 7. Misra SP, Dwivedi M (2007) Role of intravenously administered hyoscine butyl bromide in retrograde terminal ileoscopy: a randomized, double-blinded, placebocontrolled trial. World J Gastroenterol 12:1820–1823 8. Korman LY, Overholt BF, Box T et al (2003) Perforation during colonoscopy in endoscopic ambulatori surgical centers. Gastrointest Endosc 58:554–557

9. Woltjen JA (2005) A retrospective analysis of cecal barotrauma caused by colonoscope air flow and pressure. Gastrointest Endosc 61:37–45 10. Bernstein C, Thorn M, Monsees K et al (2005) A prospective study of factors that determine cecal intubation time at colonoscopy. Gastrointest Endosc 61:72–75 11. American Society for Gastrointestinal Endoscopy (1999) Principles of training in gastrointestinal endoscopy. Gastrointest Endosc 49:845–853 12. Powell N, Knight H, Dunn J, Saxena V, Mawdsley J, Murray C, Hoare J, Teare J, McNair A (2011) Images of the terminal ileum are more convincing than cecal images for verifying the extent of colonoscopy. Endoscopy 43:196–201 13. Kudo S, Tamura S, Nakajima T et al (1996) Diagnosis of colorectal tumorous lesions by magnifying endoscopy. Gastrointest Endosc 44:8–14 14. Gono K, Yamazaki K, Doguchi N et al (2003) Endoscopic observation of tissue by narrow band illumination. Opt Rev 10:1–5 15. Machida H, Sano Y, Hamamoto Y et al (2004) Narrowband imaging in the diagnosis of colorectal mucosal lesions: a pilot study. Endoscopy 36:1094–1098 16. Konerding MA, Fait E, Gaumann A (2001) 3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon. Br J Cancer 84:1354–1362 17. Skinner SA, Frydman GM, Obrien PE (1995) Microvascular structure of benign and malignant tumors of the colon in humans. Dig Dis Sci 40:373–384 18. Chiu HM, Chang CY, Chen CC et al (2007) A prospective comparative study of narrow-band imaging, chromoendoscopy and conventional colonoscopy in the diagnosis of colorectal neoplasia. Gut 56:373–379 19. Pohl J, Nguyen-Tat M, Pech O, May A, Rabenstein T, Ell C (2008) Computed virtual chromoendoscopy for classification of small colorectal lesions: a prospective comparative study. Am J Gastroenterol 103:562–569

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The Importance of Complete Colonoscopy and Exploration of the Cecal Region Kuangi Fu, Takahiro Fujii, Takahisa Matsuda, and Yutaka Saito

2.1

The Importance of a Complete Colonoscopy

Ever since case-control studies demonstrated the ability of flexible sigmoidoscopy (FS) to decrease colon cancer mortality by 60–70%, it has become the most frequently recommended modalities for colon cancer screening [1]. Recent reports, however, have shown that FS may miss proximal neoplasms or cancers [2]. Moreover, the National Polyp Study found that the incidence of colorectal cancer (CRC) in an adenoma-bearing cohort that had undergone clearing colonoscopy was reduced by 76–90% compared to reference populations [3]. It is obvious that examination of the left colon alone misses right-sided lesions. Thus, while colonoscopy is more time-consuming and resource-demanding, in addition to causing greater patient discomfort and with a higher rate of complications due to bowel cleansing and the endoscopic procedure, it is widely appreciated as the most sensitive colonic imaging test for adenomas. An additional advantage of colonoscopy is that it allows the removal of precancerous polyps at the time of their detection. A right-sided aging-related shift in the location of the initial development of colorectal adenomas was recently reported, based on repeated colonoscopies in subjects with no neoplasms [4]. Recurrent adenomas after polypectomy also tend to develop at locations

K. Fu (&) Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan e-mail: [email protected]

proximal to the initial adenomas [5]. Accordingly, total colonoscopy is needed for surveillance, regardless of the initial adenoma site. Moreover, the distribution of carcinoma and of adenomatous polyps in the colorectum likewise shows a proximal shift with age and female gender [6, 7]. Clinically, right-sided cancer is likely to be detected at a more advanced stage, with severe symptoms such as passage trouble or abdominal mass. Morphologically, the frequency of tumors with a flat-type appearance is significantly higher in right-sided than in left-sided colon cancers, while polypoid-type lesions are substantially more dominant in the left colon [8]. Histopathologically, poorly differentiated, mucinous, and signet-ring cell tumors are frequently seen in the right colon [9]. From a molecular aspect, the right-sided tumors that predominate in the elderly are those with a high frequency of CpG island methylation and those with microsatellite instability (MSI), in which there is often methylation of the promoter region of the hMLH1 mismatch repair gene [10]. A newly proposed disease entity, serrated polyps, comprises hyperplastic polyps, traditional serrated adenomas (TSAs), and sessile serrated adenomas (SSAs), which have also been described as sessile serrated polyps (SSPs) [11]. SSAs/SSPs are more prevalent in the proximal colon and lack classic dysplasia but may have mild cytologic atypia, whereas TSAs are more prevalent in the rectosigmoid and have cytologic dysplasia. SSAs/SSPs, particularly those with foci of classic histologic dysplasia, are considered the likely precursor lesions to sporadic MSI-H colon cancer, as determined in studies of their molecular profiles, which have shown inactivation through methylation of genes such as the MLH-1 DNA repair genes and/or

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Table 2.1 Endoscopic treatment at the National Cancer Center Hospital, Tokyo, Japan (January 1998 until September 2006) Adenoma (14,285) Cecum

860 (87.2%)

M-Ca (1,717)

SM-Ca (302)

119 (12.1%)

7 (0.7%)

Total (%) 986 (6.0)

Ascending

2,942 (90.2%)

283 (8.7%)

35 (1.1%)

3,260 (20.0)

Transverse

4,004 (93.3%)

244 (5.7%)

42 (1.0%)

4,290 (26.3)

Descending

1,723 (92.8%)

122 (6.6%)

11 (0.6%)

1,856 (11.4)

Sigmoid

3,298 (84.2%)

513 (13.1%)

104 (2.7%)

3,915 (24.0)

Rectum

1,458 (73.0%)

Total (%)

14,285 (87.6)

436 (21.8%)

0-6-methylguanine DNA methyltransferase (MGMT) [12]. The presence of SSAs/SSPs (C10 mm in size) is also reported to be a risk factor for CRC, particularly of the proximal colon [13].

2.2

103 (5.2%)

1,717 (10.5)

The Importance of Exploring the Cecum

It has been known for many years that colorectal adenoma and CRC have different distributions in the colon. The anatomic distribution of adenomas in the colon was described in previous reports (e.g., [14]) that included autopsy and endoscopic studies. Autopsy studies show a relatively even distribution of adenomas throughout the colon whereas cancer is more frequent in the distal colon and rectum. In those studies, the incidence of adenomas located in the cecum varied from 2 to 67%. However, in some reports fewer than 200 cases were evaluated. By contrast, endoscopic studies evaluated more than 200 cases (one was based on 6,942 cases), reporting cecal adenomas in 2–20%. Based on data from the National Cancer Center, the incidence of early colorectal neoplasia involving the cecum, as determined from tumors resected endoscopically, is 6.0% (Table 2.1) whereas the incidence of CRCs located in the cecum, as determined from surgically removed tumors, is 6.8% (Table 2.2). Although the incidence of colorectal neoplasia in the cecum is lower than in other sites, it should be kept in mind that some non-polypoid neoplasias, including SSAs/SSPs or laterally spreading tumor, can occur at this site, especially at the periphery of the appendiceal orifice, and are endoscopically detectable. Obviously, visualization of the appendiceal orifice and ileocecal valve confirms a complete total colonoscopy.

302 (1.9)

2.3

Case Presentation

2.3.1

Case 1

1,997 (12.3) 16,304 (100.0)

A 74-year-old woman underwent total colonoscopy because of a positive fecal occult blood test. During conventional endoscopic observation, a superficially reddish area was detected on the ileocecal valve (Fig. 2.1a). Narrow-band imaging revealed a flat brownish lesion (Fig. 2.1b). Chromoendoscopy, performed using indigo-carmine spraying, further demonstrated a non-granular type of laterally spreading tumor (LST-NG), 20 mm in diameter, on the ileocecal valve (Fig. 2.1c). Magnification with chromoendoscopy using indigo-carmine and crystal-violet staining showed a type IIIL pit pattern, according to Kudo’s classification, which is a good indication for endoscopic resection (Fig. 2.1d, e). The tumor was completely removed en bloc with endoscopic submucosal dissection (Fig. 2.1f). Histologically, the lesion was identified as a tubular adenoma with high- and lowgrade atypia, with the cut end free of adenoma.

2.3.2

Case 2

A 48-year-old man underwent total colonoscopy because of a positive fecal occult blood test. A flat elevated lesion was detected in the cecum near the orifice of the appendix (Fig. 2.2a). Chromoendoscopy using indigo-carmine day spraying showed a lesion covered by a small amount of mucus, even after vital water washing (Fig. 2.2b). Magnification after chromoendoscopy revealed an elongated type II pit pattern at the periphery, with features similar to those of a type IIIL pit pattern (Fig. 2.2c). A dilated type II pit pattern

2

The Importance of Complete Colonoscopy and Exploration of the Cecal Region

Table 2.2 Surgery at the National Cancer Center Hospital, Tokyo, Japan (January 1998 until September 2006)

Fig. 2.1 a–f A non-granular type of laterally spreading tumor (LST-NG), 20 mm in diameter, is seen on the ileocecal valve

Cecum

Early (618)

Advanced (2,651)

39

183

9 Total (%) 222 (6.8)

Ascending

73

322

395 (12.1)

Transverse

58

215

273 (8.4)

Descending

26

117

143 (4.4)

Sigmoid

166

660

826 (25.3)

Rectum

256

1,154

1,410 (43.0)

Total (%)

618 (18.9)

2,651 (81.1)

3,269 (100.0)

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Fig. 2.2 a–d A sessile serrated adenoma/polyp is detected in the cecum adjacent to the orifice of appendix

was detected in the central flat area (Fig. 2.2d). These endoscopic results suggested a large hyperplastic polyp, or an SSA/SSP. The lesion was completely removed en bloc with endoscopic mucosal resection (the conventional lift and cut technique). Histologically, the lesion was identified as an SSA/SSP.

5.

6. 7.

References 1. Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS (1992) A case control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 326:653–657 2. Brenner H, Arndt V, Sturmer T, Stegmaier C, Ziegler H, Dhom G (2001) Long-lasting reduction of risk of colorectal cancer following screening endoscopy. Br J Cancer 85:972–976 3. Winawer SJ, Zauber AG, Ho MN et al (1993) Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 329: 1977–1981 4. Yamaji Y, Mitsushima T, Ikuma H, Watabe H, Okamoto M, Yoshida H, Kawabe T, Wada R, Omata M (2006) Right-side

8.

9. 10.

11.

12.

shift of colorectal adenomas with aging. Gastrointest Endosc 63(3):453–458 (quiz 464) Yamaji Y, Mitsushima T, Yoshida H, Watabe H, Okamoto M, Ikuma H, Wada R, Kawabe T, Omata M (2007) Rightside shift of metachronous colorectal adenomas after polypectomy. Scand J Gastroenterol 42(12):1466–1472 Distler P, Holt PR (1997) Are right- and left-sided colon neoplasms distinct tumors? Dig Dis 15:302–311 Gonzalez EC, Roetzheim RG, Ferrante JM et al (2001) Predictors of proximal vs. distal colorectal cancers. Dis Colon Rectum 44:251–258 Nawa T, Kato J, Kawamoto H, Okada H, Yamamoto H, Kohno H, Endo H, Shiratori Y (2008) Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol 23(3):418–423 Iacopetta B (2002) Are there two sides to colorectal cancer? Int J Cancer 101:403–408 Hawkins N, Norrie M, Cheong K et al (2002) CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability. Gastroenterology 122:1376–1387 Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM (2003) Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol 27(1):65–81 Snover DC (2011) Update on the serrated pathway to colorectal carcinoma. Hum Pathol 42(1):1–10

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The Importance of Complete Colonoscopy and Exploration of the Cecal Region

13. Hiraoka S, Kato J, Fujiki S, Kaji E, Morikawa T, Murakami T, Nawa T, Kuriyama M, Uraoka T, Ohara N, Yamamoto K (2010) The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology 139(5):1503–1510 (1510.e1-3)

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14. Neugut AI, Jacobson JS, Rella VA (1997) Prevalence and incidence of colorectal adenomas and cancer in asymptomatic persons. Gastrointest Endosc Clin N Am 7(3):387–399

3

What are the Correct Indications for Ileoscopy? Antonello Trecca, Fabio Gaj, Stefano Serafini, Gabriele Marinozzi, and Marco Silano

3.1

Introduction

Exploration of the terminal ileum has rapidly gained the interest of the international literature, starting from the first report in 1972 by Nagasako [1]. Over the past few decades, technical refinements of the endoscopic equipment and the resulting improvement in knowledge have simplified intubation of the last centimeters of the terminal ileum. These advances have been confirmed in several reported experiences in which the terminal ileum was intubated during colonoscopy, with a success rate in experienced hands of 74–100% [2–4]. The importance of terminal ileoscopy (TI) is that it offers proof that a total colonoscopy has been performed, since previously established signs, such as visualization of the semilunar folds of the cecal region and transillumination of the right lower abdominal quadrant, are considered too subjective and have since been abandoned. Cherian and Singh [5] were among the first to stress the need for adequate training in TI as an essential step in becoming a proficient colonoscopist. The study demonstrated that the procedure times for colonoscopies performed by trainees were significantly longer than those by the consultant, but that after adequate training, the ileum could be successfully intubated in 85% of patients (Fig. 3.1).

A. Trecca (&) Endoscopic and Operative Gastroenterology Units, USI Group, Rome, Italy e-mail: [email protected]

Iacopini et al. [6] prospectively investigated the learning curve and skill retention for ileoscopy, showing that competency in ileocecal valve intubation, with a success rate of 80% and ileal exploration of about 16 cm, could be achieved after 50 procedures. Training was based on the observation of ten TIs performed by senior endoscopists and with a selfassessment made hands-on. The experience of the endoscopist and ileocecal valve morphology were the only two independent variables influencing the success of the procedure, and the tolerability of TI was inversely proportional to the duration of the exploration (Fig. 3.2). A useful investigation also can be defined as one in which the result will alter the management or add confidence to the clinician’s diagnosis. Thus, when debating the merits of TI we have to consider the success rate, diagnostic yield, duration, and above all the capacity to modify the clinical results [7].

3.2

Indications and Results of Terminal Ileoscopy

In patients with diarrhea, right lower quadrant abdominal pain, and anemia, intubation of the terminal ileum is of pivotal importance to exclude Crohn’s disease (CD), especially in case of a negative colonoscopy (Table 3.1). The estimated diagnostic yield is about 20% in patients with chronic diarrhea and 40% in those in whom inflammatory bowel disease (IBD) is suspected (Fig. 3.3). Evidence was provided that intubation of the terminal ileum during colonoscopy can yield success rates of 74% to as high as 100% without a significant

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Fig. 3.1 Endoscopic view of the terminal ileum a after immersion with saline and b after dye spraying with indigo carmine 0.4%

prolongation of the procedure. The median duration of the procedure was 55 s (55–180 s), without an increased intra-examination risk [8–11] (Table 3.2). Nevertheless, even if the additional time needed for TI during colonoscopy may seem short, considering the annual workload of most hospitals, instituting the procedure routinely would correspond to an additional 200 colonoscopies annually, as calculated in 2001 by the British Society of Gastroenterology Working Party [12]. Thus, whether TI should be performed in unselected patients remains a matter of debate among the experts, although the majority seems to agree that the examination is unnecessary given the high percentage of negative findings. All studies, including those with the bias of being retrospective, found that the incidence of pathologic findings during TI performed in asymptomatic patients was only 0.3–4.6%. According to Yoong and Heymann, a clinical impact in terms of a change in management was noted in only half of the patients examined [13]. Nonetheless, if we consider the spectrum of IBD it seems obvious that a negative TI examination can better validate a diagnosis of ulcerative colitis with evident colonic lesions or support a definitive diagnosis of indeterminate, collagenous, ischemic, or drug-induced colitis [14, 15]. Ileal intubation should be performed only when abnormal findings or changes in patient management are expected [16, 17]. As provocatively suggested by Cherian and Singh, however, TI is as much a part of colonoscopy as the exploration of the second portion of the duodenum is during esophagogastroduodenoscopy; this is especially the case given the shortness of the learning curve. As summarized by Ansari et al. [2]: ‘‘Added time, technical difficulty and limited yield are not valid reasons for choosing not to perform ileoscopy’’ (Fig. 3.4).

Fig. 3.2 Advanced cancer located just in front of the ileocecal valve

Table 3.1 Absolute indications for ileoscopy • Chronic diarrhea • Right lower quadrant abdominal pain • Abnormal imaging findings • Suspicion of inflammatory bowel disease • Family history of Crohn’s disease

3.3

The Contribution of Histology

Another topic of discussion is TI with biopsy, which can add important information about the histology of the mucosa and thereby increase the diagnostic yield of the procedure. Thus, the question again arises [18, 19]: should histological examination of the terminal ileum always be performed or should it be selective? The answer is complex if we consider that a definitive diagnosis is based on the combination of clinical data, laboratory values, microbiological

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What are the Correct Indications for Ileoscopy?

15

Table 3.2 The role of ileoscopy during colonoscopy First author

Patients (n)

Ileal intubation (%)

Abnormal findings (%)

Ileal findings and GI symptoms (%)

Yoong [13]

2149

346 (16)

16 (4)

8 (50)

Kundrotas [4]

270

213 (79)

1 (0.3)

0

Zwas [3]

144

138 (95)

12 (5)

8 (65)

Iacopini [6]

600

–(91)

15 (5.5)

6 (2.2)

Kennedy [16]

30000

6408 (21)

68 (1)

6 (10)

Bhasin [17]

66

57 (86)

13 (22)

8 (14)

Geboes [7]

300

–

123/257 (48)

Symptoms of IBD: 125/257 (49)

Cherian [5]

2537

–(71.5)

IBD (16) Unselected (2.7)

IBD: 19 Unselected (7.4)

Morini [26]

156

149/156 (95)

47/138 (34)

CND: 8/138 (5.8)

Ansari [2]

120

117 (97)

24 (20.5)

Abdominal pain 15/86 (17.4)

IBD Chronic or persistent diarrhea, CND chronic non-bloody diarrhea Fig. 3.3 a Multiple aphthoid lesions in the terminal ileum; b magnifying view

examinations, and radiology, endoscopy and histology findings, each of which plays a specific role. Undoubtedly TI with biopsies provide more detailed information than obtained by any other radiological examination, such as small bowel followthrough (SBFT) or small-bowel enema, in detecting terminal ileal pathology. Indeed, TI has a sensitivity and specificity of 100% in the diagnosis of CD and in the detection of microscopic inflammatory changes of the mucosa [20, 21]. The introduction of capsule endoscopy into the clinical setting has revolutionized the diagnostic approach to the terminal ileum, as outlined by Hara et al. in a prospective comparative study between capsule endoscopy, computed tomographic (CT) enterography, colonoscopy with ileoscopy, and SBFT [22]. The highest diagnostic yield for CD, even if not statistically significant, was gained by capsule endoscopy. SBFT failed to depict a stricture in one patient, which resulted in surgical removal of the capsule. CT enterography and SBFT depicted extra-intestinal findings (e.g., mesenteric adenopathy

Fig. 3.4 Meckel’s diverticulum of the terminal ileum is clearly visible after chromoendoscopy

in two patients, perianal and enterocolic fistulas in one patient) not detected endoscopically, confirming that each imaging modality has its specific role and that patients with negative TI and suspected CD should undergo capsule enteroscopy in order to

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Fig. 3.5 Mucosal bridges of the left colon a in a patient with chronic ulcerative colitis and b ileoscopy with negative findings

Fig. 3.6 Diffuse nodular lymphoid hyperplasia of the terminal ileum with active bleeding

Fig. 3.7 Diffuse and serpiginous ulcerative lesions of the terminal ileum in patient with Crohn’s disease Table 3.3 Absolute indications for ileoscopy and biopsy

exclude lesions that may be present anywhere along the bowel (Fig. 3.5). In a retrospective study by McHugh et al. [23], comprising more than 414 consecutive patients submitted to ileoscopy and biopsy, TI was negative in 81% and the findings were histologically normal in 82%, supporting the conclusion that both procedures are unnecessary routinely because of their high cost and lengthy duration. The diagnostic yield of biopsies varies with the specific endoscopic findings and is greatest when the endoscopist reports ‘‘ileitis,’’ ulcers, or erosions and discouraging in patients with a normal-appearing mucosa. A cost-effective strategy would be to include TI for patients with suspected IBD or those with abnormal findings involving the terminal ileum. Other reports on unselected patients seem to confirm these data, with evidence of macroscopic and/or microscopic abnormalities in 1.8–7.4% and increasing up to 19% only in patients with IBD [24].

• Suspicion of Crohn’s disease • Chronic diarrhea • HIV-infected patients • Suspicion of tuberculosis • Ileal lesions at ileoscopy

Two major indications for ileocolonoscopy have so far evident: in patients in whom CD is suspected and in those with diarrhea, ileocolonoscopy with biopsies is the recommended diagnostic procedure and, in optimal conditions, results in a final diagnosis in up to 99% of the cases [25] (Fig. 3.6). Several other clinical conditions should be kept in mind when considering the wide spectrum of IBD: backwash ileitis, which has an incidence of 6% in patients with ulcerative colitis, a family history of CD, and all patients in whom other imaging modalities raise suspicion of CD. In this setting, the

3

What are the Correct Indications for Ileoscopy?

17

Fig. 3.8 a Severe atrophic changes in the terminal ileum after chromoendoscopy with indigo carmine 0.4% and b magnified view

Fig. 3.9 a Sessile polyp at terminal ileoscopy. b The villous structure is clearly visible after the instillation of saline

histology of the terminal ileum is undoubtedly the only available basis for the diagnosis. Chronic non-bloody diarrhea should be considered another indication for TI and biopsy only after it has been correctly classified on a clinical basis. In unselected patients, the diagnostic yield of TI is approximately 5%, while in a series of 156 patients with chronic non-bloody diarrhea, CD, nonspecific ileitis, and nodular lymphoid hyperplasia were significantly more frequent in patients than in controls, confirming the ability of TI to detect alterations in this group of patients such that the gain in the final diagnosis of CD was 5.8% [26]. The passage of blood makes an accurate exploration indispensable, while in case of an inflammatory condition histology cannot rule out a definitive diagnosis (Fig. 3.7). Terminal ileoscopy should always be attempted but only in case of mucosal lesions integrated with biopsy. A normal terminal ileum should be biopsied only in HIV-infected patients or in patients from countries in which intestinal tuberculosis is highly likely [27–29] (Table 3.3).

3.4

Open Issues

A possible link between TI and histology can be provided by the benefits gained from the most recent technological advances, which have opened up new horizons for the modern endoscopist by improving diagnosis as well as the selection of patients for target biopsy [30, 31]. Conventional or virtual chromoendoscopy in combination with magnification accentuates the unique appearance of the ileal mucosa’s surface structure and capillary vessels. Confocal laser endomicroscopy provides such high resolution of the columnar villous epithelium that it is possible to observe discrete goblet cells, mononuclear cells, intraepithelial lymphocytes, and erythrocytes within the subepithelial stromal capillary net [32, 33]. The ability to enhance the mucosal appearance of the terminal ileum surely provides an optimal modality to study villous morphology and to detect any minimal reduction or shortening of the villi.

18

A. Trecca et al.

The diagnostic yield can be improved particularly in patients with celiac disease or early CD, as demonstrated in a study of 143 patients examined by magnification. In this study, 6 out of 10 patients with Celiac disease were correctly diagnosed by endoscopy alone. Among the four patients with CD, two had ileal lesions detectable only on magnifying view [34] (Fig. 3.8). Nevertheless, the exact role of these imaging modalities should be confirmed in larger series of patients, which would contribute to establishing a modern diagnostic flow-chart able to increase the clinical results obtainable for each and every patient [35] (Fig. 3.9).

5.

6.

7.

8.

9.

10.

3.5

Conclusions

Terminal ileoscopy currently represents an effective procedure for the assessment of diseases of the terminal ileum. The possibility of gaining a highly specialized expertise after adequate training confirms that this examination establishes proficiency as a colonoscopist. The diagnostic yield of TI, considering the brief duration of the procedure and the lowest risk of complication, merit the use of this procedure in patients in whom there is suspicion of CD, as based on right lower abdominal quadrant pain, anemia, and suspicious imaging results. The endoscopist should always attempt TI, obtaining biopsy material when lesions to the terminal ileum are identified. The role of emerging technologies, while promising, remains to be better validated in clinical practice. A well-performed TI represents the best method to correctly select patients who would most benefit from other procedures and it offers a fast-track approach to diseases of the gut.

11.

12.

13. 14.

15.

16.

17.

18.

References 1. Nagasako K, Yazawa C, Takemoto T (1972) Biospy of the terminal ileum. Gastrointest Endosc 19:7–10 2. Ansari A, Soon SY, Saunders BP et al (2003) A prospective study of the technical feasibility of ileoscopy at colonoscopy. Scand J Gastroenterol 38:1184–1186 3. Zwas FR, Bonheim NA, Berken CA et al (1995) Diagnostic yield of routine ileoscopy. Am J Gastroenterol 90: 1441–1443 4. Kundrotas LW, Clement DJ, Kubik CM et al (1994) A prospective evaluation of successful terminal ileum

19.

20.

21.

22.

intubation during routine colonoscopy. Gastrointest Endosc 40:544–546 Cherian S, Singh P (2004) Is routine ileoscopy useful? An observational study of procedure times, diagnostic yield nad learning curve. Am J Gastroenterol 99:2324–2329 Iacopini G, Frontespezi S, Vitale MA, Villotti G, Bella A, D’Alba L, De Cesare A, Iacopini F (2006) Routine ileoscopy at colonoscopy: a prospective evaluation of learning curve and skill-keeping line. Gastrointest Endosc 63:250–256 Geboes K (2007) The strategy for biopsies of the terminal ileum should be evidence based. Am J Gastroenterol 102:1090–1092 Borsch G, Schmidt G (1985) Endoscopy of the terminal ileum. Diagnostic yield in 400 consecutive examinations. Dis Colon Rectum 28:499–501 Israel DM, McLain BI, Hassall E (1994) Successful pancolonoscopy and ileoscopy in children. J Pediatr Gastroenterol Nutr 19:283–289 Marshall JB, Barthel JS (1993) The frequency of total colonoscopy and terminal ileum intubation in 1990s. Gastrointest Endosc 39:518–520 Bernstein C, Thom M, Monsees K et al (2005) A prospective study of factors that determine cecal intubation time at colonoscopy. Gastrointest Endosc 61:72–75 Working Party of the British Society of Gastroenterology Endoscopy Committee (2001) Provision of endoscopy related services in district general hospitals, working party report. London Yoong KKY, Heymann T (2006) It is not worthwhile to perform ileoscopy on all patients. Surg Endosc 20:809–811 Biancone L, Calabrese E, Palmieri G, Petruzziello C, Onali S, Sigismondo Sica G, Cossignani M, Condino G, Das KM, Pallone F (2008) Ileal Lesions in patients with ulcerative colitis after ileorectal anastomosis: relationship with colonic metaplasia. WJG 14:5290–5300 Jeong SH, Lee KJ, Kim YB, Kwon HC, Sin SJ, Chung JY (2007) Diagnostic value of terminal ileum intubation during colonoscopy. J Gastroenterol Hepatol 23:51–55 Kennedy G, Larson D, Wolff B, Winter D, Petersen B, Larson M (2008) Routine ileal intubation during screening colonoscopy: a useful maneuver? Surg Endosc 22:2606–2608 Bhasin DK, Goenka MK, Dhavan S, Dass K, Singh K (2000) Diagnostic value of ileoscopy. A report from India. J Clin Gastroenterol 31:144–146 Geboes K, Ectors N, D’Haens G et al (1998) Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of IBD. Am J Gastroenterol 93:201–206 Coremans G, Rutgeerts P, Geboes K et al (1984) The value of ileoscopy with biopsy in the diagnosis of intestinal Crohn’s disease. Gastrointest Endosc 30:167–172 Fireman Z, Kopelman Y (2008) Small Bowel Capsule Endoscopy: have we conquered the last frontier? IMAJ 10:298–301 Byrne MF, Power DG, Keeling AN, Kay E, Murray FE, Patchett SE (2004) Combined terminal ileoscopy and biopsy is superior to small bowel follow-through in detecting terminal ileal pathology. Dig Liver Dis 36:147–152 Hara AK, Leighton JA, Heigh RI, Sharma VK, Silva AC, De Petris G, Hentz JG, Fleischer DE (2006) Crohn disease of the small bowel: preliminary comparison among ct enterography,

3

23.

24.

25.

26.

27.

28. 29.

What are the Correct Indications for Ileoscopy? capsule endoscopy, small-bowel follow through and ileoscopy. Radiology 238:128–134 McHugh JB, Appelman HD, McKenna BJ (2007) The diagnostic value of endoscopic terminal ileum biopsies. Am J Gastroenterol 102:1084–1089 Shah RJ, Fenoglio-Preiser C, Bleau BL et al (2001) Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea. Am J Gastroenterol 96:1091–1095 Sultan S, Mitchell RM (2004) The importance of ileoscopy in suspected small bowel disease. Eur J Gastroenterol Hepatol 16:359 Morini S, Lorenzetti R, Stella F et al (2003) Retrograde ileoscopy in chronic nonbloody diarrhea: a prospective case-control study. Am J Gastroenterol 98:1512–1515 Sato S, Yao K, Yao T, Schlemper RJ, Matsui T, Sakurai T, Iwashita A (2004) Colonoscopy in the diagnosis of intestinal tubercolosis in asymptomatic patients. Gastrointest Endosc 59:362–368 Misra SP, Misra V, Dwivedi M (2007) Ileoscopy in patients with ileocolonic tubercolosis. WJG 13:1723–1727 Misra SP, Dwivedi M, Misra V (2006) Ileoscopy in 39 hematochezia patients with normal colonoscopy. WJG 12:3102–3104

19 30. Tanaka S, Kaltenbach T, Chayama K et al (2006) Highmagnification colonoscopy. Gastrointest Endosc 64:604–613 31. Technology Commitee ASGE (2009) Technology status evaluation report on high-resolution and high-magnification endoscopes. Gastrointest Endosc 69:399–407 32. Siegel LM, Stevens PD, Lightdale CJ et al (1997) Combined magnification endoscopy with chromoendoscopy in the evaluation of patients with suspected malabsorption. Gastrointest Endosc 46:226–230 33. Cammarota G, Martino A, Pirozzi GA et al (2004) Direct visualization of intestinal villi by high-resolution magnifying upper endoscopy: a validation study. Gastrointest Endosc 60:732–738 34. Trecca A, Gaj F, Gagliardi G, Calcaterra R, Battista S, Silano M (2008) Role of magnified ileoscopy in the diagnosis of cases of coeliac disease with predominant abdominal symptoms. Scand J Gastroenterol 44:320–324 35. Dionisio PM, Gurudu SR, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, Shiff AD, Sharma VK (2010) Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a meta-analysis. Am J Gastroenterol 105:1240–1248

4

Contribution of New Technologies to Endoscopic Imaging Giuseppe Galloro, Luca Magno, Simona Ruggiero, Ferdinando Fusco, and Tiziana Rappa

4.1

Introduction

The importance of the earliest possible detection of digestive malignant lesions has fueled the development of new high-technology endoscopic systems, the so-called powerful endoscopes. Comparable to the rapid development of chip technology, the optic features of the new powerful endoscopes offer a resolution able to reveal surface details of the gastrointestinal tract. Some of these technologies increase diagnostic performance by improving resolution, others by modifying the chromatic spectrum of the endoscopic image. The augmented endoscopic vision is due to the use of either charge-coupled device (CCD) or central processing unit (CPU; endoscopic processor) features. The new generation of gastric and colonic endoscopic probes enable high-resolution endoscopy, highmagnification endoscopy (magnifying and zoom), and computed virtual chromoendoscopy (CVC) whereas the enteroscopes that are currently available are restriced to CVC types, without high-resolution or magnifying-zoom endoscopic capabilities. Consequently, the only way to perform high-resolution or magnifying-zoom endoscopy in the ileum is by using a new-generation coloscope, inserted through the

G. Galloro (&) Department of General, Geriatric, Oncologic Surgery and Advanced Technology, Unit of Surgical Digestive Endoscopy, University of Naples ‘‘Federico II’’—School of Medicine, Naples, Italy e-mail: [email protected]

ileocolic valve, while CVC involves the use of a dedicated enteroscope. Nevertheless, Pentax has developed a new type of enteroscope, the VSB-2990i HD, able to perform high-resolution enteroscopy, although study data have yet to be reported.

4.2

High-Resolution and High-Magnification Endoscopy

4.2.1

Technological Status

The video capabilities of the color images generated by standard definition (SD) endoscopes are based on traditional television (TV) broadcast formats [1, 2]. SD signals offer images in a 4:3 aspect ratio, with image resolutions of 640–700 pixels width by 480–525 pixels or ‘‘lines’’ of height (approximately 367,000 pixels) [2]. SD endoscopes are equipped with CCD chips that produce an image signal of 100,000–400,000 pixels, which are displayed in SD format. Advances in CCD technology have resulted in smaller CCDs with an increased number of pixels and higher resolution. The CCDs used in current highresolution or high-definition (HD) endoscopes produce signal images with resolutions between 850,000 and 1 million pixels. The general definition of HD and high-resolution images is an image with more than 650–720 lines of resolution (height) [3]. Moreover, images may be progressive or interlaced. With progressive (p) images, lines are scanned consecutively and the image is created 60 times per second, whereas with interlaced (i)

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_4, Ó Springer-Verlag Italia 2012

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images, every other line is scanned and the image is created in two passes at 30 times per second each. HD video imaging can be displayed in either TV or computer monitor format. The 16:9 aspect ratio is not useful to display images from round endoscopic lenses. Historically, endoscopic images are typically displayed in a 4:3 aspect ratio, to match the standard aspect ratios of SD TV and because this ratio provides the highest possible pixel density and resolution, given the shape of the lens. The display in computer monitor formats uses progressive scanning and is not restricted by broadcast HD formats or aspect ratios. Monitors have traditionally had 4:3 aspect ratios but recently 5:4 ratios have become more popular. Current high-resolution endoscopic CCDs display images in either 4:3 or 5:4 aspect ratios [3]. It is important to recognize that, to provide a true HD image, each component of the system (e.g., endoscope CCD, processor, monitor, and transmission cables) must be HD compatible. Three different high-resolution endoscope systems are currently commercially available: (1) Olympus high-resolution endoscopes were designed based on the commercial availability of TVs and recorders for output onto HDTVs. The output from the endoscope is enhanced to 1080i; however, the endoscopic image itself is displayed within a 1,280 9 1,024-pixel frame. (2) Fujinon high-resolution endoscopes were designed for output onto computer monitors. The first Fujinon CCD chips were 1,077 9 788 pixels and their output was equivalent to XGA monitors [2]; however, current endoscopes have an output of 1,280 9 960 pixels. The actual resolution of the CCD is proprietary information. The newest processors enhance the image to 1080i. (3) Pentax Medical high-resolution endoscopes were designed for output onto computer monitors. The Pentax CCD is 1,280 9 1,024 pixels and displays at native resolution. High-resolution endoscopes magnify the endoscopic images 30–35 times. Zoom endoscopes are defined by the capacity to perform optical zooming through a movable lens in the tip of the endoscope [4]. Optical zoom provides a closer image of the target while maintaining image display resolution. This is distinguished from electronic magnification, which simply moves the image closer on the display and results in a decreased number of pixels that compose the area of the display, with no improvement in resolution [5]. With the proper processor,

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conventional endoscopes permit an electronic magnification of 1.5–2. Although standard endoscopes magnify images 30–35 times, zoom endoscopes can optically magnify images up to 150 times, depending on the size of the monitor.

4.2.2

Implementation of High-Resolution and High-Magnification Endoscopy in Ileoscopy

Usually, the target of high-resolution and highmagnification endoscopy is a qualitative diagnosis that differentiates between neoplastic and non-neoplastic lesions, based on the study of the pit pattern (superficial orifices of the glandular crypts on the digestive mucosal surface) [6, 7]. To date, there are limited analyses of magnification endoscopy in small-bowel diseases, although there have been a few promising reports of targeting duodenal biopsies in celiac sprue or malabsorption [8–10]. One of these studies, conducted on 34 patients with either celiac or tropical sprue, found that magnifying chromoendoscopy was better than standard endoscopy in identifying duodenal villous atrophy and therefore improved target biopsies [8]. Another study showed that high-resolution endoscopy had 95% sensitivity, 99% specificity, 95% positive predictive value, and 99% negative predictive value to detect the presence of any duodenal villous abnormality [9]. Some authors have proposed a new role for highresolution and high-magnification enteroscopy in the study of primary intestinal lymphangiectasia, i.e., to show the dilated capillary vessels in intestinal villi and the loss of lymph fluid into the gastrointestinal tract [11]. As in the duodenum, high-resolution and highmagnification endoscopy also could be used in the ileum, i.e., in targeted biopsies and in the study of mucosal areas where histopathologic abnormalities are most likely to be present. However, this application awaits further and more specific evaluation. Moreover, cost-effectiveness studies are needed before these techniques can be recommended for clinical practice. A Japanese paper [12] suggested the use of highmagnification ileoscopy (using a zoom colonscope through the ileocolic valve) to evaluate the presence of Peyer’s patches, which on magnifying endoscopy are seen as irregularly shaped, granular, dome-like elevations and irregularly arranged villi in the terminal ileum. The histologic finding of microgranulomas,

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Contribution of New Technologies to Endoscopic Imaging

lymphoid hyperplasia, and the presence of M cells at scanning electron microscopy confirms that these areas are Peyer’s patches [13]. Peyer’s patches, as detected by magnifying endoscopy and electron microscopy, may provide insights into the pathogenesis of Crohn’s disease. Another important indication of high-resolution and high-magnification endoscopy of the small bowel, and the ileum in particular, is the zoom endoscopic followup of transplanted patients, to monitor potential small-bowel allograft rejection. In fact, with recent improvements in surgical techniques and immunosuppressive drugs, small-bowel transplantation has become a desirable and potentially life-saving alternative for patients with short-gut syndrome or other problems causing intestinal failure [14–16]. The early diagnosis of graft rejection is extremely important because rapid progression to severe rejection can occur without proper treatment, and advanced stages of rejection are associated with poor outcomes [17, 18]. The technology and clinical protocols for monitoring graft function and for treating acute rejection are still in the early stages of development. Frequent biopsies of the small-bowel graft are critical for detecting the presence of acute cellular rejection. While random mucosal biopsy provides detailed information about a very small area, the endoscopic view can provide information about large areas, thus allowing rapid assessment of the overall health of the graft mucosa. In addition, this approach is essential for obtaining histologic specimens [19–21]. Unfortunately, standard endoscopy is not powerful enough to provide an accurate view of the mild changes that occur in the early phase of small-bowel rejection [22, 23] whereas high-resolution and high-magnification ileoscopy, performed by a zoom colonscope through a surgically created ileostomy, allows direct visualization of the villi and crypt areas, thereby providing a more accurate overall evaluation of the graft mucosa [22]. Indeed, in skilled hands, zoom endoscopic evaluation of villous shortening, villous blunting, background erythema, villous congestion, and mucosal friability (confirmed by histologic findings on target biopsies) has achieved a sensitivity of 45%, a specificity of 98%, a positive predictive value of 82%, and a negative predictive value of 88% [24]. In pediatric patients, these values are, respectively, 61, 84, 57, and 86%. In conclusion, the enhanced capability afforded by zoom ileoscopy in the assessment of graft mucosal health has been shown

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to provide useful information, thus enabling a rapid diagnosis that, along with the presenting clinical symptoms, can determine the need to treat histologically diagnosed early rejection.

4.3

Computed Virtual Chromoendoscopy

4.3.1

Technological Status

Computed virtual chromoendoscopy is a real-time, on-demand endoscopic imaging technique in which the spectroscopic characteristics of the videoendoscopic systems are adjusted by using a frame sequential lighting method [25], thereby allowing enhanced visualization of the vascular network and mucosal surface texture and, in turn, improved tissue characterization, differentiation, and diagnosis. CVC is considered a potential alternative to traditional chromoendoscopy, providing contrast enhancement of tissue surface structures; however, it has not been as extensively studied as chromoendoscopy. Currently, three different CVC systems are commercially available: olympus narrow-band imaging (NBI), Fujinon Intelligent Color Enhancement (FICE), and Pentax i-Scan. Standard videoendoscope systems use the entire spectrum of visible light (400–700 nm). These so-called white-light imaging endoscopic systems are designed to simulate daylight and to examine tissues in their natural colors. The videoendoscopic images can be obtained by one of two different systems: the red–green–blue (RGB) sequential and color CCD systems [26]. In the RGB sequential system, light from a xenon arc lamp is filtered through a rotating broadband RGB filter located between the lamp and the endoscope’s light guide to obtain sequential bursts of red, green, and blue light that give rise to the visual strobe effect. After tissue illumination, the reflected red, green, and blue tissue images are sequentially captured by a monochromatic CCD at the tip of the endoscope and transmitted to a video processor. The three images are fed into the electron guns that illuminate the red, green, and blue phosphor dots on the monitor, respectively, to create a final composite image in full natural color [27]. The color CCD system uses a micromosaic color filter mounted over the CCD itself. Continuous whitelight illumination from the xenon lamp is delivered to the tissue by the endoscope’s light guide, with the

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reflected light and image created on the CCD surface then processed by circuitry in the video processor prior to display. Similar to the RGB system, tissue structures that heavily reflect red, green, and blue light are displayed on the R, G, and B video channels on the video monitor, respectively [27]. The NBI system (Olympus Medical Systems, Tokyo, Japan) emphasizes the mucosal microvasculature and is able to identify vascular alterations indicative of pathologic conditions [28–31]. It consists of narrow bandpass filters placed in front of a conventional white-light source to produce a contrast between vascular structures and surrounding mucosa. Unlike the initial three-band NBI prototypes, currently available NBI systems use just two different narrowband filters [27]. The first provides tissue illumination in the blue spectrum of light at 415 nm, emphasizing capillaries in the superficial mucosal layer and showing them in brown; the second provides tissue illumination in the green spectrum of light at 540 nm, which corresponds to the secondary hemoglobin absorption peak, and emphasizes deeper mucosal and submucosal venular vessels, displaying them in cyan. The NBI system can be coupled with electronic or optical (zoom) magnification for enhanced visualization of mucosal details. The FICE system (Fujinon, Saitama, Japan), is marketed as a digital image processing technique that enhances mucosal surface structures by using selected wavelengths of light in reconstituted virtual images. Unlike NBI (which uses optical filters), FICE is software-driven and uses an image-processing algorithm that is based on spectral estimation methods. In this technology, developed by Professor Yoichi Miyake [32], a standard image captured by a color CCD videoendoscope is sent to a spectral estimation matrix processing circuit contained in the EPX 4400 video processor. Here, the spectra of the various pixels corresponding to the conventional image are mathematically estimated. Since the pixels’ spectra are well known, it is possible to implement imaging at a single wavelength. The single-wavelength images are randomly selected and assigned to red, green, and blue to build and display a CVC-enhanced color image. The digital processing system is able to immediately switch between an ordinary image and a FICE image by a simple push of a button on the handle of the endoscope. Moreover, the wavelengths most suitable for examination can be selected because of the system’s variable

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setting functions, with up to ten preselected settings. These ten presets can be customized and configured from a very large number of wavelength permutations since any of 60 wavelengths (400–695 nm, in increments of 5 nm) can be used as input into any of the three (R, G, and B) channels [33]. A programmable push button on the handle of the endoscope enables switching between the conventional white-light image and the corresponding FICE image of a single specified preset. FICE can also be coupled with electronic or optical (zoom) magnification for enhanced visualization of mucosal details. The i-Scan (Pentax, Tokyo, Japan) is the latest CVC technology and it is marketed as a digital-contrast method among endoscopic imaging techniques [34]. This CVC system has three modes of image enhancement: (1) surface enhancement (SE), in which the structures are enhanced through recognition of the edges; (2) contrast enhancement (CE), in which the depressed areas and differences in structure are enhanced through colored presentation of low-density areas; and (3) tone enhancement (TE), in which individual organs are enhanced by modifying the combination of RGB components for each pixel. SE and CE allow switching among three enhancement levels (low, medium, and high), and TE among three objects (esophagus, stomach, and colon). Since the three modes (SE, CE, and TE) are arranged in series, two or more of them can be applied at one time. Switching the levels or modes of enhancements is done on a real-time basis, without any time lag, by pushing a relevant button, thus enabling efficient endoscopic observation [35]. With SE, the difference in luminance intensity between the pixels concerned and the surrounding pixels is analyzed and the edge components are enhanced. With ordinary enhancement, minor changes in structure are perceived as noise. Adjustment of the noise-erasure function allows more evident enhancement of the edges [36]. Compared to normal images, SE images do not differ in brightness and differ little in color. With CE, areas of lower luminance intensity are compared to surrounding pixels and identified on the basis of pixel-wise luminance intensity data, followed by relative enhancement of the B component through slight suppression of the R and G components in the low-luminance area. As a result of CE, the low luminance area is stained slightly bluish white and minute irregularities on the mucosal surface are enhanced [37]. There is no change in image brightness and very little

4

Contribution of New Technologies to Endoscopic Imaging

change in the color of the images, only the slight bluishwhite staining of depressed areas. With TE, the RGB components of the endoscope image are divided into their respective components (R, G, and B) which are converted independently along the tone curve, followed by their re-synthesis to yield a reconstructed image. The tone curve is depicted by plotting input (on the x axis) against output (on the y axis) and can be changed, by modification of the parameters into S and J types. If the tone curve assumes an S-type form, the high R-component area is shifted to an even higher range of R to enhance the color tone R, or the low R-component area is shifted to an even lower range of R to elevate the sensitivity to the GB components, thus allowing clear enhancement of the differences in color tone. If the tone curve assumes a J-type form, the R component is shifted completely to a low R range, thus elevating the overall sensitivity to GB components and the brightness/darkness contrast [35–38]. Thus far, no complications have been attributed to the use of NBI, FICE, or i-Scan [27]. Endoscopic systems equipped with CVC are more expensive than those with white light but formal cost analyses have yet to be reported. Moreover, there are no unique current procedural terminology (CPT) codes for NBI, FICE, or i-Scan [27].

4.3.2

Implementation of Computed Virtual Chromoendoscopy in Ileoscopy

The usual target of CVC systems is a qualitative diagnosis that distinguishes between non-neoplastic, dysplastic, and neoplastic lesions, based on the study and evaluation of the superficial microvascular network and surface texture of the mucosa [25–27]. Studies have been conducted to evaluate and assess the role of CVC enteroscopy in the characterization of various small-bowel diseases. Since Fujinon double balloon enteroscopy (DBE) was the first balloon-guided enteroscopy system on the market and it is supplied with FICE, most of these studies have involved this system. FICE was shown to be a feasible virtual chromoendoscopy technique, enhancing surface visualization of the small-bowel mucosa [39–41]. Specifically, DBE with FICE effectively evaluated small-bowel polyps in familial adenomatous polyposis (FAP), in

25

which the pit pattern resembles that of colon polyps [39]. FICE better delineates these polyps while contrast enhancement allows the detection of a greater number of lesions. However, despite the increased visualization of diminutive adenomatous polyps in FAP, FICE does not modify either the diagnosis or the mode of therapy. FICE is useful to better delineate the margin of adenomatous polyps from healthy surrounding mucosa [40]. This is especially important in polypectomies, mucosal and submucosal resections, and argon-plasma ablation. Margin evaluation more accurately confirms complete eradication. However, it remains to be determined whether FICE, when used in the detection of small-bowel polyps, can differentiate low- from high-grade dysplasia. FICE also does not improve the definition of Peutz–Jeghers syndrome polyps [39] while in nodular lymphoid hyperplasia, white light and FICE seem to be equivalent in characterizing the mucosa and delineating pseudopolyps [39–42]. Other studies have reported that FICE improves the visibility of normal mucosal vessels and aids in the detection of vascular ectasias not seen by whitelight endoscopy [42]. Specifically, FICE can be used to clearly demarcate angioectasias, which appear as homogeneous spots within the surrounding mucosa. The theoretical advantage of FICE is that, due to the large number of possible filters, the mucosa can be evaluated with various virtual dyes [39] whereas the NBI system from Olympus has only one set of filters. However, there are as yet no studies showing that a greater number of options results in better characterization of either the mucosa or mucosal lesions. In analyses of villous architecture, the colorcontrast capabilities of FICE and the addition of endoscopic magnification allow high-quality characterization of small-bowel villi. In addition, FICE well demonstrates the submucosal and intravillous capillary network. In primary intestinal lymphangiectasia, better appreciation of engorged mucosal villi and lymphangiectasias is achieved with CVC than with white-light endoscopy [43]. The use of balloon-assisted enteroscopy has been assessed in small-bowel follicular lymphoma, revealing multiple nodular lesions, elevated white patches, and scattered white polypoid lesions [44]. In this case, either NBI [45] or FICE [46] improves the diagnosis, demonstrating small, whitish nodules and a coiled, elongated vascular pattern within the elevated lesions.

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The latest technological development is the implementation of FICE software within the workstation of the video capsule system [47]. This allows the assessor to flexibly choose between standard imaging and three different FICE patterns with different wavelength selections, resulting in optimal mucosal imaging. FICE-enhanced capsule endoscopy improves the contrast of vascular and mucosal patterns. Preliminary clinical tests suggest that the properties of FICE are not only of theoretical value but can also make a real difference in clinical practice, in case of obscure digestive bleeding, suspected Crohn’s disease, the differentiation of neoplastic from non-neoplastic lesions, and the surveillance of polyposis syndromes. However, there are major differences between the application of FICE in flexible endoscopy versus capsule endoscopy, since image resolution with capsule endoscopy is much lower than with high-resolution video technology.

4.4

Confocal LASER Endoscopy

4.4.1

Technological Status

Confocal laser endomicroscopy (CLE) is a new endoscopic technology developed to obtain veryhigh-resolution images of the gastrointestinal mucosa. It is based on tissue illumination using low-power laser, with subsequent detection of the fluorescence reflected from the tissue through a pinhole [48]. The term confocal refers to the alignment of the illumination and collection systems in the same focal plane [49]. The laser light is focused at a selected depth in the tissue of interest and reflected light is then refocused onto the detection system by the same lens. Only returning light refocused through the pinhole is detected. Light reflected and scattered at other geometric angles from the illuminated object or refocused out of plane with the pinhole is excluded from detection [50]. This dramatically increases image resolution, providing a nearly histological examination or ‘‘optical biopsy’’ of the superficial layer of the digestive tract [51–53]. Confocal imaging systems can be based on tissue reflectance or tissue fluorescence. Those based on tissue reflectance do not require the use of contrast agents but are plagued by technical problems and low resolution, thus compromising their clinical utility [54, 55], whereas systems based on tissue fluorescence use local and/or intravenous

contrast agents and generate high-quality images comparable with those obtained by traditional histology preparations [56, 57]. Two types of confocal endoscopes are commercially available. The first is integrated into the distal tip of a conventional upper endoscope (EG-3870CIK; Pentax, Tokyo, Japan) or colonoscope (EC-3870CILK; Pentax). The second uses a dedicated confocal miniprobe with a laser microscope (Mauna Kea Technologies, Paris, France) inserted through the accessory channel of a traditional endoscope. Both instruments have CE code and US Food and Drug Administration authorization, and both have different depths of imaging, field of views, and lateral resolutions. The Mauna Kea confocal gastrointestinal miniprobes include the CholangioFlex, GastroFlex (standard and UHD), and ColoFlex (standard and UHD). All of these probes generate dynamic images, with 12 frames per second, and are reusable for approximately 20 studies. The depth of imaging is 40–70 lm for CholangioFlex probes, 70–130 lm for GastroFlex and ColoFlex probes, and 55–65 lm for GastroFlexUHD and ColoFlexUHD probes. The maximal field of view is 325 lm for CholangioFlex probes, 600 lm for GastroFlex and ColoFlex probes, and 240 lm for GastroFlexUHD and ColoFlexUHD probes. The lateral resolution is 3.5 lm for CholangioFlex, GastroFlex, and ColoFlex probes, and 1 lm for GastroFlexUHD and ColoFlexUHD [58, 59]. The Pentax confocal microscope integrated into conventional endoscopes collects images at a scan rate of 1.6 frames per second (1024 9 512 pixels) or 0.8 frames per second (1024 9 1024 pixels), with an adjustable depth of scanning ranging from 0 to 250 lm, a field of view of 475 9 475 mm, a lateral resolution of 0.7 lm, and an axial resolution of 7 lm [50–61]. The fluorescent contrast agents for CLE can be administered intravenously or topically. Intravenous fluorescein (Pharmalab, Lane Cove, New South Wales, Australia) distributes throughout the extracellular matrix of the surface epithelium and lamina propria but does not stain cell nuclei [49]. Topically administered acriflavin (Sigma Pharmaceuticals, Clayton, Victoria, Australia), tetracycline, or cresyl violet (AnaSpec, San Jose, CA, USA) stains the cell nuclei of the surface epithelium but does not penetrate the deeper layers of the mucosa [49]. Acriflavin is a mutagenic dye and a potential human carcinogen, which will no doubt limit its clinical utility [62].

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Contribution of New Technologies to Endoscopic Imaging

After contrast administration, the tip of the confocal endomicroscope or miniprobe is positioned in gentle contact with the area of interest to obtain highresolution confocal images. Accumulated images can be saved for postprocedural analysis.

4.4.2

Implementation of Confocal Laser Endoscopy in Ileoscopy

Several studies have addressed the clinical applications of CLE [63]. The extreme enlargment and the highresolution of the confocal images, providing a nearly histologic examination, make CLE perfectly suitable for the study of early displastic-neoplastic changes of the gastrointestinal tract. Thus far, there have been no studies on CLE applications in small-bowel diseases but confocal endomicroscopy will likely improve the characterization and diagnosis of celiac disease, Crohn’s disease, infections, vasculitis, mesenteric ischemia, and angiodysplasias, among others.

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colon, oesophagus, duodenal ampulla and lung. Aliment Pharmacol Ther 28:854–867 Tajiri H, Matsuda K, Fujisaki J (2002) What can we see with the endoscope? Present status and future perspectives. Digestive Endoscopy 14:131–137 Higuchi K, Komatsu K, Wakamatsu H et al (2007) Small intestinal follicular lymphoma with multiple tumor formations diagnosed by double-balloon enteroscopy. Intern Med 46:705–710 Liu YX, Huang LY, Bian XP, Cui J, Xu N, Wu CR (2008) Fuji intelligent chromo endoscopy and staining technique for the diagnosis of colon tumor. Chin Med J 121:977–982 Pohl J, Aschmoneit I, Schuhmann S, Ell C (2010) Computed image modification for enhancement of smallbowel surface structures at video capsule endoscopy. Endoscopy 42:490–492 Wang TD (2005) Confocal microscopy from the bench to the bedside. Gastrointest Endosc 62:696–697 Polglase AL, McLaren WJ, Skinner SA et al (2005) A fluorescence confocal endomicroscope for in vivo microscopy of the upper- and the lower-GI tract. Gastrointest Endosc 62:686–695 Technology Commitee ASGE (2009) Confocal laser endomicroscopy. Gastrointest Endosc 70:197–200 Wang TD, Van Dam J (2004) Optical biopsy: a new frontier in endoscopic detection and diagnosis. Clin Gastroenterol Hepatol 2:744–753 Yoshida S, Tanaka S, Hirata M, Mouri R, Kaneko I, Oka S, Yoshihara M, Chayama K (2007) Optical biopsy of GI lesions by reflectance-type laser-scanning confocal microscopy. Gastrointest Endosc 66(1):144–149 Aisenberg J (2008) Gastrointestinal endoscopy nears ‘‘the molecular era’’. Gastrointest Endosc 68:528–530 Inoue H, Cho JY, Satodate H et al (2003) Development of virtual histology and virtual biopsy using laser-scanning confocal microscopy. Scand J Gastroenterol 237:37–39 Yoshida S, Tanaka S, Hirata M et al (2007) Optical biopsy of GI lesions by reflectance-type laser-scanning confocal microscopy. Gastrointest Endosc 66:144–149 Sakashita M, Inoue H, Kashida H et al (2003) Virtual histology of colorectal lesions using laser-scanning confocal microscopy. Endoscopy 35:1033–1038 Kiesslich R, Neurath MF (2006) Chromoendoscopy and other novel imaging techniques. Gastroenterol Clin North Am 35:605–619 Becker V, Vercauteren T, von Weyhern CH et al (2007) High-resolution miniprobe-based confocal microscopy in combination with video mosaicing. Gastrointest Endosc 66:1001–1007 von Delius S, Feussner H, Wilhelm D et al (2007) Transgastric in vivo histology in the peritoneal cavity using miniprobe-based confocal fluorescence microscopy in an acute porcine model. Endoscopy 39:407–411 Goetz M, Hoffman A, Galle PR et al (2006) Confocal laser endoscopy: new approach to the early diagnosis of tumors of the esophagus and stomach. Future Oncol 2:469–476 Hurlstone DP, Kiesslich R, Thomson M et al (2008) Confocal chromoscopic endomicroscopy is superior to

4

Contribution of New Technologies to Endoscopic Imaging

chromoscopy alone for the detection and characterisation of intraepithelial neoplasia in chronic ulcerative colitis. Gut 57:196–204 62. Burleson GR, Caulfield MJ, Pollard M (1979) Ozonation of mutagenic and carcinogenic polyaromatic amines and polyaromatic hydrocarbons in water. Cancer Res 39: 2149–2154

29 63. Mönkemüller K, Neumann H, Fry LC (2009) endoscopic examination of the small bowel: from standard white light to confocal endomicroscopy. Clinic Gastroenterol Hepatol 7:11–12

5

Ileoscopy in Coeliac Disease Marco Silano, Emilio Gentile Warschauer, Gabriele Marinozzi, Giuseppe Cerno, and Antonello Trecca

5.1

Introduction

Celiac disease is a permanent autoimmune enteropathy that is triggered, in genetically determined individuals, by the ingestion of gluten, an alcohol-soluble protein storage compound present in wheat [1, 2]. The main protein component of wheat gluten is gliadin and there are similar proteins in rye and barley (secalin and hordein, respectively). In addition to gliadin, gluten contains a second major protein, glutenin, and both are active in celiac disease [3]. Celiac disease is the most common food intolerance worldwide and its reported incidence is increasing annually. Although 1% of the population of Europe and North America is estimated to be affected by celiac disease, the majority of celiac patients are either not diagnosed or are misdiagnosed [1]. This is because the disease manifests as a wide spectrum of gastroand extra-intestinal signs and symptoms of broadly varying severity, including asymptomatic forms [3, 4]. Often, the diagnosis of celiac disease is made by antibody screening among first-degree relatives of the patient, as they are at high risk of develop the disease [5]. The presumed diagnosis is based upon the detection of serum IgA anti-transglutaminase antibody and is confirmed by the histological findings of the characteristic lesions of the small-bowel mucosa: villous atrophy, hyperplasia of the crypts, and T-cell

M. Silano (&) Division of Food and Science, Human Nutrition and Health, Istituto Superiore di Sanità, Rome, Italy e-mail: [email protected]

infiltration of the lamina propria, along with an increase in intraepithelial lymphocytes [4, 6]. Duodenoscopy with biopsy is still the gold standard for the diagnosis of celiac disease, even if the diagnostic value of serological tests is quite high. Since the mucosal lesions can be patchy, multiple biopsy samples should be taken during duodenoscopy [7, 8]. Presently, the only known treatment of celiac disease is the life-long withdrawal of gluten-containing foods from the diet. In celiac patients, a gluten-free diet results in remission, while the re-introduction of gluten into the diet causes disease relapse [9]. Compliance with a gluten-free diet is difficult because of the widespread distribution and consumption of cereal-based foods, but strict adherence is necessary to reduce mortality and morbidity. Poor adherence to a gluten-free diet increases the celiac patient’s risk of developing life–threatening complications, such as enteropathy-associated T-cell lymphoma and intestinal adenocarcinoma [5, 10, 11].

5.2

Videocapsule and Capsule Endoscopy in the Evaluation of Celiac Disease

Nowadays, imaging of the small bowel can be improved by the use of videocapsule endoscopy, a non-invasive technique that enables the study of the entire length of the intestine and, in celiac disease, demonstrates the extent of the affected bowel segments. The procedure can confirm the adequate healing of the mucosa in response to a gluten-free diet and detect malignancies in patients at high risk. Many authors have reported that the most important endoscopic signs of celiac disease, such as scalloping folds,

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_5, Ó Springer-Verlag Italia 2012

31

32

Fig. 5.1 Ileoscopy in a celiac patient a Conventional ileoscopic view showing granular appearance of ileal mucosa. b After virtual chromoendoscopy and magnifying view, partial villous atrophy of ileal mucosa is clearly visible. c Ileal atrophy at high-

M. Silano et al.

resolution magnification. d–f Corresponding biopsy of terminal ileum (H&E stain) shows the villous atrophy, along with the increased intraepithelial lymphocyte count (magnification 1009), confirmed on immunostaining for CD3 CX10, and Dx20

mosaicism, micronodularity, and the reduction of folds, intraepithelial lymphocytes ([25/100 enterocytes) is can be detected by capsule endoscopy even if these more frequently detected [15, 16]. We recently reported on a series of 143 patients findings are suggestive of villous atrophy. Rondonotti et al. [12] showed that 66.6% of patients had an exten- who underwent ileoscopy. TI mucosal lesions were sion of the mucosal changes seen at capsule endoscopy determined in 21 patients. Among them, ten patients beyond the proximal small bowel and 11.1% had lesions showed villous atrophy at ileoscopy that was clearly visible only with a magnifying view. Six of those that involved the small bowel entirely. The accuracy of conventional endoscopy with a patients had an intraepithelial lymphocyte count magnifying view has increased with respect to the [25/100 enterocytes. Upper intestinal lesions condetection of celiac disease, such that it is possible to firmed the diagnosis of celiac disease [17, 18]. These findings demonstrate that inflammation assovisualize even minimal changes in the mucosa (Fig. 5.1). In the celiac patient, patchy atrophy is easily ciated with celiac disease may involve the entire intesdiagnosed, greatly facilitating target biopsy. Both the tinal tract and that in some cases ileoscopy can drive the ‘‘immersion technique’’ and magnifying endoscopy diagnosis of the disease. Therefore, endoscopists should [13, 14] show sensitivity, specificity, and positive and be aware of the possibility of finding celiac-disease-type negative predictive values close to 100% in case of inflammation even during a TI endoscopic examination. total villous atrophy, while for less severe mucosal As imaging techniques become increasingly sensitive, damage, as in Marsch I and II villous atrophy, the more accurate results will be achieved in the diagnosis and management of celiac disease. results are encouraging. An increasing numbers of patients are diagnosed with celiac disease after showing intestinal symptoms that result in the patients undergoing a lower endos- References copy rather than an upper endoscopy. The mucosa of the terminal ileum (TI) of celiac patients is often 1. Fasano A, Catassi C (2001) Curent approaches to diagnosis and treatment of celiac disease: an evolving spectrum. normal and the finding of villous atrophy is rare, Gastroenterology 120:636–651 whereas infiltration of the lamina propria by

5

Ileoscopy in Coeliac Disease

2. Kagnoff ME (2005) Overview and pathogenesis of celiac disease. Gastroenterology 128:S10–S18 3. Shewry PR, Tatham AS, Kasarda DD (1992) Celiac disease. Blackwell Scientific, London 4. Alaedini A, Green PHR (2005) Narrative review: Celiac disease: understanding a complex autoimmune disorder. Ann Intern Med 142:289–298 5. Green PHR, Jabri B (2003) Coeliac disease. Lancet 362:383–391 6. Rostom A, Dubé C, Cranney A, Saloojee N, Sy R, Garritty C, Sampson M, Zhang L, Yazdi F, Mamaladze V, Pan I, MacNeil, J, Mack D, Patel D, Moher D (2005) The diagnostic accuracy of serological test for celiac disease: a systematic review. Gastroenterology 128: S38–S46 7. Hopper AD, Cross SS, Sanders DS (2008) Patchy villous atrophy in adult patients with suspect gluten intolerance: is a multiple duodenal biopsy strategy appropriate? Endoscopy 40:219–224 8. Bonamico M, Mariani P, Thanasi E, Ferri M, Nenna R, Tiberti C, Mora B, Mazzilli MC, Magliocca FM (2004) Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr 38:204–207 9. Green PH, Cellier C (2007) Celiac disease. N Engl J Med 357:1731–1743 10. Catassi C, Bearzi I, Holmes GK (2005) Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology 128:S79–S86 11. Silano M, Volta U, De Vincenzi A, Dessì M, De Vincenzi M (2008) Collaborating Centers of the Italian Registry of the Complications of Coeliac Disease. Effect of a gluten-

33

12.

13.

14.

15.

16. 17. 18.

free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci 53:972–976 Rondonotti E, Spada C, Cave D, Pennazio M, Riccioni ME, De Vitis I, Schneider D, Sprujevnik T, Villa F, Langelier J, Arrigoni A, Costamagna G, de Franchis R (2007) Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study. Am J Gastroenterol 102:1624–1631 Cammarota G, Martino A, Pirozzi GA, Cianci R, Cremonini F, Zuccala G, Cuoco I, Ojetti V, Montalto M, Vecchio FM, Gasbarrini A, Gasbarrini G (2004) Direct visualization of intestinal by high-resolution magnifying upper endoscopy: a validation study. Gastrointest Endosc 60:732–738 Petroniene R, Dubcenco E, Backer JP, Ottaway CA, Tang SJ, Zanati SA, Streutker CJ, Gardiner GW, Warren RE, Jeejeebhoy KN (2005) Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement. Am J Gastroenterol 100:685–694 Hopper AD, Hurlstone DP, Leeds JS, McAlindon ME, Dube AK, Stephenson TJ (2006) The occurrence of terminal ileal histological abnormalities in patients with coeliac disease. Dig Liver Dis 38:815–819 Dickey W, Hughes DF (2004) Histology of the terminal ileum in coeliac disease. Scand J Gastroenterol 39:665–667 Sundar N, Muktar A, Finnie IA (2003) Ileocolonoscopic diagnosis of celiac disease Endoscopy 35:374 Trecca A, Gaj F, Gagliardi G, Calcaterra R, Battista S, Silano M (2009) Role of magnified ileoscopy in the diagnosis of cases of coeliac disease with predominant abdominal symptoms. Scand J Gastroenterol 44:320–324

6

The Role of Ileoscopy in Inflammatory Bowel Disease Bjorn Rembacken and Mohammed Thoufeeq

6.1

Introduction

Total colonoscopy, including the exploration of the terminal ileum, can assure the visualization of mucosal lesions in patients with inflammatory bowel disease (IBD) [1]. Ileocolonoscopy provides an accurate evaluation of the early and characteristic lesions of IBD, their severity, and their extension. Other, radiological imaging modalities, i.e., ultrasonography, computed tomography (CT) scan, and magnetic resonance imaging (MRI), are needed to describe the intestinal wall as they are able to identify penetrating and stricture-related complications. Nonetheless, endoscopy plays a fundamental role, allowing not only morphological evaluation but also an assessment of healing of the intestinal mucosa. These parameters are very useful in the clinical management of affected and treated patients. Recently, the therapeutic arsenal for IBD has progressed, with the introduction of biologics but also the improved awareness of how and when treatment should be administered [2]. In particular, the step-up approach has gained a broader consensus for the treatment of patients with refractory disease that is either unresponsive to conventional therapies or steroid-dependent [3]. Moreover, endoscopy, with its capacity to accurately describe mucosal lesions and mucosal healing, has been used to predict clinical outcome in patients with Crohn’s disease (CD) and

B. Rembacken (&) Department of Endoscopy, General Infirmary Hospital, Leeds, UK e-mail: [email protected]

ulcerative colitis (UC), identifying those patients eligible for more aggressive therapies or even surgery.

6.2

Endoscopic Evaluation in Crohn’s Disease

Ileocolonoscopy in patients with CD can describe the minimal changes seen in the mucosa, such as erythema, swelling, nodularity, and aphthoid ulcerations, as well as more ‘‘advanced lesions,’’ such as ulcers of variable size and depth, the cobblestone appearance of the intestinal wall, and the presence of strictures (Figs. 6.1 and 6.2). These endoscopic lesions can be quantified by validated endoscopic indices of disease activity. For example, the CD endoscopic index of severity (CDEIS) is based on the recognition of elementary lesions (non-ulcerated lesions, superficial and deep ulcerations) in association with an evaluation of their surface properties, dividing the intestine in five segments (ileum, right colon, transverse, left colon, and sigmoid and rectum). A simple endoscopic score for CD (SES-CD) also has been proposed and correlates well with the CDEIS, which is still considered difficult to apply for clinical purposes [4–6] (Table 6.1). Both scores can be used for the definition of disease activity and to describe mucosal healing. In a retrospective series of 78 patients submitted to surgical therapy for CD, endoscopic detection of severity correlated well with the histology performed on colectomy specimens, whereas this was not case using clinical and biological severity criteria [7]. The most important endoscopic criteria of severity were: (1) deep ulcerations eroding the muscle layer, (2) deep ulcerations not

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_6,  Springer-Verlag Italia 2012

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36

Fig. 6.1 Advanced lesions in a patient with Crohn’s disease (CD): ulcers of variable size and depth are visible during retrograde ileoscopy

B. Rembacken and M. Thoufeeq

ileocolonoscopy predicts a more aggressive course of the disease with an increased number of surgical procedures than required by patients without severe lesions (relative risk 5.43, 95% CI: 2.64–11.18) [8]. During the last decade, with the introduction of new treatment approaches, the concept of mucosal healing has gained much greater relevance in the clinical setting [9]. Previously, mucosal healing was seen only in one-third of the patients with steroidinduced clinical remissions and endoscopic recovery was not associated with a low risk of relapse; thus, steroid-treated patients were evaluated mainly using the clinical index (CDAI). However, it is now recognized that mucosal healing predict treatment efficacy and the reduced frequency of surgery and hospitalizations [10]. CD patients submitted to surgical resections need strict follow-up as they are at a higher risk for disease recurrence. Rutgeerts et al. [11], in 1990, showed that ileocolonoscopy performed within 1 year of surgery is able to predict disease outcome. Accordingly, the authors proposed a score that is now widely used in clinical practice and has been accepted as part of the ECCO guidelines (Table 6.3).

6.3

Fig. 6.2 Advanced lesion in CD: a stricture of the ileocecal valve

eroding the muscle layer but involving more than onethird of the mucosal area; and (3) mucosal detachment at the edge of ulcerations. At least one of these criteria was found in 95% of patients with severe anatomic lesions as determined on colectomy specimens. The CDEIS, however, does not correlate with the clinical index (CDAI) nor with the biological activity of the disease, which is mainly determined by measuring C-reactive protein (Table 6.2). Retrospective studies have shown that when endoscopic examination of CD patients with active disease highlights deep and extensive ulcerations of the ileocolonic mucosa,

Endoscopic Evaluation in Ulcerative Colitis

The endoscopic evaluation of patients with UC is based on mucosal patterns, which are similar to those already described in CD patients. The endoscopist should search for an abnormal vascular pattern, granularity, and ulcers. There are currently nine different scores proposed for use in clinical practice (Table 6.4). In patients who suffer a severe attack of UC, colonoscopy has demonstrated its utility in describing the extensive deep ulcerations; however, the examination should be performed with caution and only after radiological exclusion of megacolon and with minimal insufflation of air (Figs. 6.3 and 6.4). Carbonnel et al. [12] showed the feasibility of colonoscopy without significant complications in patients with severe UC; in that study, the presence of deep ulcerations was confirmed in nearly all of the patients who subsequently underwent colectomy. In another series in which the response to medical treatment was evaluated, severe ulcerations were

6

The Role of Ileoscopy in Inflammatory Bowel Disease

37

Table 6.1 Simple endoscopic score for Crohn’s disease (SES-CD) Variable

0

1

2

3

Size of ulcers

None

Aphthous ulcers (0.1–0.5 cm)

Large ulcers (0.5–2 cm)

Very large ulcers ([2 cm)

Ulcerated surface

None

\10%

10–30%

[30%

Affected surface

Unaffected segment

\50%

50–75%

[75%

Strictures

None

Single, can be passed

Multiple, can be passed

Cannot be passed

Table 6.2 Crohn’s disease activity index (CDAI) Clinical or laboratory variable

Weighting factor

Number of liquid or soft stools each day for 7 days

92

Abdominal pain (graded from 0–3 on severity) each day for 7 days

95

General well being, subjectively assessed from 0 (well) to 4 (terrible) each day for 7 days

97

Presence of complications

a

920

Taking Lomotil or opiates for diarrhea

930

Presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite)

910

Hematocrit of \0.47 in men and \0.42 in women

96

Percentage deviation from standard weight

91

The index consists of eight factors, each summed after adjustment with a weighting factor. The table shows the components of the CDAI and the weighting factors. The remission of Crohn’s disease is defined as a fall in the CDAI of \150. Severe disease is defined as a value [450. Most major research studies on medications in Crohn’s disease define response as a [70 point fall of the CDAI a One point each is added for each set of complications: • The presence of joint pain (arthralgia) or frank arthritis • Inflammation of the iris or uveitis • Presence of erythema nodosum, pyoderma gangrenosum, or aphthous ulcers • Anal fissures, fistulae, or abscesses • Other fistulae • Fever during the previous week

Table 6.3 Endoscopic score of activity from Rutgeerts et al. (from [11]) Grade

Endoscopic findings

0

No lesions in the distal ileum

1

C5 aphthous lesions

2

[5 aphthous lesions with normal mucosa between the lesions, or skip areas of larger lesions confined to the ileocolonic anastomosis

3

Diffuse aphthous ileitis with diffusely inflamed mucosa

4

Diffuse inflammation with larger ulcers or stenosis

described more frequently in non-responders than in responders (91 vs. 34%, respectively; OR [ 20) [13]. In UC patients, mucosal healing should always be assessed endoscopically, even if there is no agreement regarding its definition, since the disappearance of the normal vascular pattern is considered sufficient to

determine disease progression [14]. Wright and Truelove [15] found that 40% of patients with a good response to oral and rectal steroids did not experience disease relapse after 1 year of follow-up compared to 18% of those who continued to have active endoscopic lesions. A reduced likelihood of surgery was

38

B. Rembacken and M. Thoufeeq

Table 6.4 Endoscopic indexes for ulcerative colitis activity Author [reference]

Description

Truelove 1995 [19]

Sigmoidoscopic appearance Normal or near-normal (only slight hyperemia or only slight granularity) Improved Unchanged or worse

Baron 1964 [20]

Baron score Normal (0): matt mucosa, ramifying vascular pattern clearly visible throughout, no spontaneous bleeding, no bleeding to light touch Abnormal (1): between normal (0) and moderately hemorrhagic (2) Moderately hemorrhagic (2): bleeding to light touch, but no spontaneous bleeding seen ahead of instrument on initial inspection Severely hemorrhagic: spontaneous bleeding seen ahead of instrument at initial inspection with bleeding to light touch

Feagan 2005 [21]

Modified Baron score Normal mucosa Granular mucosa with an abnormal vascular pattern (1) Friable mucosa (2) Microulceration with spontaneous bleeding (3) Gross ulceration

Powel-Tuck 1978 [22]

Sigmoidoscopic appearance Nonhemorrhagic (0): no spontaneous bleeding or bleeding to light touch Hemorrhagic (1): no spontaneous bleeding but bleeding to light touch Hemorrhagic (2): spontaneous bleeding ahead of instrument at initial inspection with bleeding to light touch

Schroeder 1987 [23]

Mayo score (sigmoidoscopic evaluation) • Normal or inactive disease (0) • Mild disease (1): erythema, decreased vascular pattern, mild friability • Moderate disease (2): marked erythema, absent vascular pattern, friability, erosions • Severe disease (3): spontaneous bleeding, ulceration

Sutherland 1987 [24]

Sutherland sigmoidoscopic mucosal appearance • Normal (0) • Mild friability (1) • Moderate friability (2) • Exudation, spontaneous hemorrhage (3)

Rachmilewitz 1989 [25]

Rachmilewitz index A: Granulation scattering reflected light: yes (0), no (2) B: Vascular pattern: normal (0), faded/disturbed (1), Completely absent (2) C: Vulnerability of mucosa: none (0), slightly increased (contact bleeding) (2); greatly increased (spontaneous bleeding) (4) D: Mucosal damage (mucus, fibrin, exudates, erosions, ulcer): none (0), slight (2), pronounced (4)

Hanauer 1993 [26]

Sigmoidoscopic index (0, normal; 1, mild; 2, moderate; 3, severe) A: Erythema (0–3) B: Friability (0–3) C: Granularity/ulceration (0–3) D: Mucus (0–3) E: Lack of mucosal vascular pattern The total score is the sum of subscores A–E

Lemann 1995, Hanauer 1998 [27]

Sigmoidoscopic inflammation grade Normal mucosa (0) Edema and/or loss of visible mucosal vascularity, granularity (1) Friability (visible, contact bleeding on examination), petechiae (2) Spontaneous hemorrhage, visible ulcers (3)

6

The Role of Ileoscopy in Inflammatory Bowel Disease

39

Fig. 6.3 Emergency colonoscopy; a Endoscopy shows massive bleeding in a patient with a previous diagnosis of ulcerative colitis; b a huge flat lesion is visible at the lower rectum

Fig. 6.4 Endoscopy performed in the same patient after 1 week of treatment. a A sessile lesion is visible at the hepatic flexure (tubular adenoma with low-grade dysplasia) not

detected at emergency endoscopy; b the flat rectal lesion detected at emergency endoscopy and after chromoendoscopy with indigo carmine 0.4%

also demonstrated in patients with mucosal healing at 5 years of follow-up [16]. Finally, since chronic inflammation of the mucosa still represents a higher risk of colorectal cancer, the endoscopist should always search for dysplastic lesions in these patients [17]. Thus, modern endoscopic imaging of the mucosa may also offer an important opportunity to improve the accuracy of the early detection of colorectal cancer in UC patients.

intensively treat these patients with the intention of sparing them surgery and its associated complications. In conclusion, as stated by Rutgeerts et al. [18], the primary goals of endoscopy in IBD patients not receiving steroid therapy should be to monitor the induction and maintenance of remission and to evaluate complete healing of the intestinal and colonic mucosa. Careful monitoring will not only allow these patients to avoid surgery and its complications, but can also result in the early detection of cancer.

6.4

Conclusions References

There is a increasing consensus that mucosal healing can identify those patients with a good response to a specific therapy. Ileocolonoscopy is of pivotal importance for the definition of elementary lesions in IBD patients and for the evaluation of mucosal healing. The assessment of mucosal morphology with respect to disease activity may help the clinician to

1. Classen M, Tytgat GNJ, Lightdale C (2010) Gastroenterological endoscopy. Thieme, Munchen 2. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P (2010) Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 362:1383–1395

40 3. Fefferman DS, Farrell RJ (2005) Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice. Clin Gastroenterol Hepatol 3:11–24 4. Mary JY, Modigliani R (1989) Development and validation of an endoscopic index of the severity for Crohn’s disease: a prospective multicentre study. Groupe d’Etudes Thérapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). Gut 30:983–998 5. Cellier C, Sahmoud T, Froguel E, Adenis A, Belaiche J, Bretagne JF, Florent C, Bouvry M, Mary JY, Modigliani R (1994) Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn’s disease. A prospective multicentre study of 121 cases. The Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives. Gut 35:231–235 6. Daperno M, D’Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P (2004) Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 60:505–512 7. Nahon S, Bouhnik Y, Lavergne-Slove A, Bitoun A, Panis Y, Valleur P, Vahedi K, Messing B, Matuchansky C, Rambaud JC (2002) Colonoscopy accurately predicts the anatomical severity of colonic Crohn’s disease attacks: correlation with findings from colectomy specimens. Am J Gastroenterol 97:3102–3107 8. Allez M, Lemann M, Bonnet J, Cattan P, Jian R, Modigliani R (2002) Long term outcome of patients with active Crohn’s disease exhibiting extensive and deep ulcerations at colonoscopy. Am J Gastroenterol 97:947–953 9. Rutgeerts P, Vermeire S, Van Assche G (2008) What is the role of endoscopy in predicting Crohn’s disease relapse or course? Inflamm Bowel Dis 14(2):S183–S184 10. Frøslie KF, Jahnsen J, Moum BA, Vatn MH (2007) Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 133:412–422 11. Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M (1990) Predictability of the postoperative course of Crohn’s disease. Gastroenterology 99:956–963 12. Carbonnel F, Lavergne A, Lémann M, Bitoun A, Valleur P, Hautefeuille P, Galian A, Modigliani R, Rambaud JC (1994) Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity. Dig Dis Sci 39:1550–1557 13. Daperno M, Sostegni R, Scaglione N, Ercole E, Rigazio C, Rocca R, Pera A (2004) Outcome of a conservative approach in severe ulcerative colitis. Dig Liver Dis 36:21–28 14. Pineton de Chambrun G, Peyrin-Biroulet L, Lémann M, Colombel JF (2010) Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol 7:15–29

B. Rembacken and M. Thoufeeq 15. Wright R, Truelove SR (1966) Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis 11:847–857 16. Sandborn WJ, Rutgeerts P, Feagan BG, Reinisch W, Olson A, Johanns J, Lu J, Horgan K, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF (2009) Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 137:1250–1260 17. Allez M, Lemann M (2010) Role of endoscopy in predicting the disease course in inflammatory bowel disease. World J Gastroenterol 16:2626–2632 18. Rutgeerts P, Vermeire S, Van Assche G (2007) Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut 56:453–455 19. Seo M, Okada M, Yao T, Okabe N, Maeda K, Oh K (1995) Evaluation of disease activity in patients with moderately active ulcerative colitis: comparisons between a new activity index and Truelove and Witts’ classification. Am J Gastroenterol 10:1759–1763 20. Baron JH, Connell AM, Lennard Jones JE (1964) Variation between observers in describing mucosal appearances in proctocolitis. Br Med J 53:89–92 21. Griffiths AM, Otley AR, Hyams J, Quiros AR, Grand RJ, Bousvaros A, Feagan BG, Ferry GR (2005) A review of activity indices and end points for clinical trials in children with Crohn’s disease. Inflamm Bowel Dis 2:185–196 22. Ritchie JK, Powell-Tuck J, Lennard-Jones JE (1978) Clinical outcome of the first ten years of ulcerative colitis and proctitis. Lancet 8074:1140–1143 23. Schroeder KW, Tremaine WJ, Ilstrup DM (1987) Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 26:1625–1629 24. Sutherland LR, Martin F (1987) 5-Aminosalicylic acid enemas in treatment of distal ulcerative colitis and proctitis in Canada. Dig Dis Sci 32:64S–66S 25. Rachmilewitz D (1989) Coated mesalazine (5-amino salicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ 6666:82–86 26. Hanauer SB (1993) Medical therapy of ulcerative colitis. Lancet 8868:412–417 27. Gasche C, Scholmerich J, Brynskov J, D’Haens G, Hanauer SB, Irvine EJ, Jewell DP, Rachmilewitz D, Sachar DB, Sandborn WJ, Sutherland LR (2000) A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 1:8–15

7

Ileoscopy in the Diagnosis of Infectious Diseases Roberto Lorenzetti, Angelo Mario Zullo, and Cesare Hassan

7.1

Introduction

Although advocated by some authors [1, 2], routine intubation of the terminal ileum during colonoscopy is not recommended because of the expected low diagnostic yield in the absence of clinical suspicion of specific ileal disease [3]. Conversely, retrograde ileoscopy is highly useful when performed in certain clinical settings, such as suspected or established inflammatory bowel diseases [4], seronegative spondylarthropathy [5], lower gastrointestinal (GI)-tract bleeding [6], human immunodeficiency virus (HIV) seropositivity [7], or in cases of chronic non-bloody diarrhea [8]. However, ileoscopy is mandatory when an infectious disease potentially involving the ileum is clinically presumed. Most studies evaluating the diagnostic yield of retrograde ileoscopy have been performed either in asymptomatic patients or in patients in whom specific ileal disease is not suspected. Therefore, acute infectious ileitis has been rarely observed in these series, as the condition is usually symptomatic. Disappointingly, the role of retrograde ileoscopy in infectious diseases that may involve the terminal ileum has not been systematically addressed. Nonetheless, the relevant role of colonoscopy with ileoscopy in the diagnosis of intestinal tuberculosis has been recently emphasized, in response to epidemiological changes in the distribution of this disease during the last several decades. In fact,

R. Lorenzetti (&) Gastroenterology Department, Nuovo Regina Margherita Hospital, Rome, Italy e-mail: [email protected]

intestinal tuberculosis, traditionally common only in developing countries, is now observed even in many developed countries, especially among immigrants, in HIV-infected individuals, and those patient treated with biological therapies [9, 10].

7.2

Intestinal Tuberculosis

Several reports have demonstrated that colonoscopy with targeted biopsies of the observed lesions is the most valuable procedure to diagnose intestinal tuberculosis [11–16]. In a review of 297 patients with intestinal tuberculosis, the distal ileum and cecum were the most frequent localizations, involved in over 40% of the cases [17]. Since mucosal lesions may be confined to the distal ileum in some patients, ileoscopy is recommended in this setting to increase the diagnostic yield of endoscopy. Indeed, in a study comprising 53 patients with suspected ileocolonic tuberculosis, the distal ileum was involved in 11 (21%) [18] and was the exclusive disease localization in two (3.8%). Other case reports confirmed this observation [16, 19]. Therefore, a diagnosis of intestinal tuberculosis may be overlooked if retrograde ileoscopy is not performed when the disease is clinically suspected. In those geographic areas where tuberculosis is endemic, ileoscopy may have a relevant role even when the symptoms suggestive of this infection are vague. Of note, in an Indian series of 39 patients undergoing colonoscopy for bleeding in whom no colonic lesions were detected, two (5.1%) cases of ileal tuberculosis were identified by ileoscopy, with a further patient diagnosed with ileal typhoid ulcers [6]. Therefore, in those clinical settings

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in which the prevalence of tuberculosis is increased, such as immigrant patients or those with immunodeficiency, ileoscopy should be performed even in the absence of specific symptoms. The endoscopic features of tuberculosis observed in the colon vary and include transverse or linear ulcers, nodules, strictures, polypoid lesions, and irregular fibrous bands forming pockets. In rare cases, an ulcerative-colitis-like picture may be present [14, 20]. Conversely, in the terminal ileum, only nonspecific ulcerations with or without nodularity are usually observed. On video capsule endoscopy, ulcers of the small bowel in patients with intestinal tuberculosis are characteristically shallow, with extensive irregular ‘‘geographic’’ borders, usually not larger than 1–2 cm, and transverse rather than the typical longitudinal ulcers seen in Crohn’s disease [21]. The diagnostic yield of biopsies for intestinal tuberculosis could be a matter for concern. Indeed, given that the specific lesions are located in the submucosa, the sensitivity of the procedure is poor. However, histological alterations are seen more often in ileal specimens than in colon biopsies, with noncaseous granulomas and collections of epithelioid cells detected in 45 and 36% of patients with ileal lesions, respectively [18]. A very low diagnostic yield (8%) is achieved when biopsies are taken from the normal-appearing colonic or ileal mucosa of patients in whom ileo-colonic involvement of tuberculosis is clinically suspected, with noncaseating granulomas observed only in the ileal specimens [22]. Diagnostic uncertainties may arise at histological assessment in geographic areas where both intestinal tuberculosis and Crohn’s disease are high prevalent [23]. In India, intestinal tuberculosis is very common, but Crohn’s disease is also increasingly reported, so that it may be difficult to rule out one or the other disease [24]. Since treatment distinctly differs, diagnostic doubt must be opportunely resolved, by taking into account clinical data, endoscopic features, and radiological findings [25, 26]. Diagnostic uncertainties may persist when only ileal lesions are detected, since the endoscopic alterations and mucosal inflammatory feature seen in Crohn’s disease and intestinal tuberculosis are similar. However, the colonic lesions are well-defined and a scoring system is available. Indeed, as shown in Table 7.1, several endoscopic features are suggestive of Crohn’s disease, whilst others are evocative of intestinal tuberculosis [25].

R. Lorenzetti et al. Table 7.1 Endoscopic feature differentiating colonic Crohn’s disease from colonic tuberculosis Crohn’s disease

Tuberculosis

Anorectal lesions

Involvement of \4 segments

Longitudinal ulcers

Transverse ulcers

Aphthous ulcers

Patulous ileocecal valve

Cobblestone aspect

Pseudopolyps

By following such a classification, a positive predictive value for Crohn’s disease of 94.9% and for intestinal tuberculosis of 88.9% can be achieved. In addition, certain histological peculiarities may be useful in distinguishing the two conditions. Typically, granulomas are smaller in Crohn’s disease than in intestinal tuberculosis, where they are multiple, confluent, and show central caseating necrosis [23, 27]. However, the small sample size and an examination restricted to the superficial portion of the mucosa could make a differential pathological diagnosis difficult.

7.3

Ileal Bacterial Infections

Acute ileitis describes a clinical picture characterized by right lower quadrant abdominal pain, diarrhea, and fever, in which ileal participation is identified or suspected. Infections or infestations are a leading cause of ileitis, and these conditions should be firstly considered in the differential diagnosis. In a recent study performed in Spain [28], a diagnostic protocol was systematically used in patients with clinically suspected ileitis. This included abdominal ultrasound and computed tomography performed in the emergency departments, and retrograde ileoscopy as second-line diagnostic tool. By following such a procedure, infectious ileitis was eventually diagnosed in one-third of the patients. Early identification avoided unnecessary laparotomies when the differential diagnosis included acute appendicitis, extrauterine pregnancy, etc. The importance of this procedure is further strengthened given the frequent false-negative results of stool culture, which can lead to an underestimation of infectious ileitis or to an incorrect diagnosis. Yersinia enterocolitica and Y. pseudotuberculosis are the most commonly detected pathogens in acute ileitis. The infection is generally acquired by the

7

Ileoscopy in the Diagnosis of Infectious Diseases

43

Fig. 7.1 Anisaki is clearly visible in gastric lumen (a); the head of nematode is fixed in the wall of the posterior gastric body (b). (Picture by A. Trecca)

Fig. 7.2 Enlarged submucosal follicole in the terminal ileum (a); ascariasis appears after biopsy (b). (Picture by A. Trecca)

Fig. 7.3 Many worms of ossiuri occupy the cecal sac (a), younger specimens in the cecal region (b). (Picture by A. Trecca)

ingestion of contaminated foods or water, and diagnosis is usually based on the isolation of Y. enterocolitica in feces and/or by elevated serum antibody titers against the bacterium. Endoscopic features of Yersinia ileitis include round or oval mucosal elevations with or without ulcers, while on the ileocecal valve and in the cecum aphthoid erosions are more frequently detected [29]. Differently from Crohn’s disease, ulcers are mostly uniform in both size and shape. The lesions invariably involve the terminal ileum, with frequent extension to both the ileocecal valve and the cecum, whilst the ascending colon is less

frequently involved. These findings are observed even 4–5 weeks following the onset of symptoms of acute ileitis, suggesting a relatively long course of the disease [30]. The Mycobacterium avium-intracellulare complex is another pathogen that can cause acute ileitis in patients with immunodeficiency, either of congenital (i.e., common variable immunodeficiency) or acquired (HIV infection) origin [7]. Although the most commonly affected site is the duodenum, involvement of the terminal ileum has been shown in 6% of the HIV patients with Mycobacterium infection [31]. Diffuse

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Fig. 7.4 A case of amoebiasis: the left colon shows many scars of the mucosa (a) and atrophic changes (b). Histology shows large numbers of trophozoites (HE and PAS stained) are clearly visible (c). (Picture by A. Trecca)

mucosal ulcerations, mucosal-fold thickening, and, less frequently, strictures are the most frequent findings at ileoscopy [32, 33]. Abdominopelvic infection with the filamentous, Gram-positive bacteria Actinomyces spp. frequently includes the ileocecal region, most likely due to physiological stasis. Although actinomycosis diagnosis at colonoscopy has been reported [34], virtually all patients are diagnosed at laparotomy with ileocecal resection [35]. Therefore, in this setting, endoscopic examination of the affected terminal ileum plays a marginal role.

detected in three (23%) out of 13 patients with duodenal evidence of infection [40]. These observations suggest that ileoscopy with biopsies in HIV patients with diarrhea increases the microsporidiosis detection rate, especially when duodenal infection is ruled out. The usefulness of random ileal biopsies in HIV patients with chronic diarrhea, even in the presence of a grossly appearing mucosa, is further strengthened by the possibility of detecting cytomegalovirus ileitis [41].

7.5 7.4

Ileal Fungal and Parasitic Infections

Ileal Protozoal Infections

Chronic diarrhea is a common problem in immunocompromised patients [36]. Examination of stool samples for bacterial and protozoal pathogens is the first diagnostic step; if these studies are negative, then the next step is colonoscopy. While the usefulness and cost-effectiveness of colonoscopy have been clearly demonstrated [37], the diagnostic yield of ileoscopy has not been systematically investigated. In patients with HIV, especially those with advanced disease, diarrhea is frequently caused by Cryptosporidium parvum. The inclusion of ileoscopy and biopsy of the terminal ileum during colonoscopy results in a significant yield in the diagnosis of microsporidiosis [38]. In a study enrolling 79 HIV patients, the additional diagnosis of microsporidiosis was made in five (6.3%) by biopsy of the terminal ileum [39]. Of note, in these cases, the coccidian infection was confined to the terminal ileum, with no additional diagnosis performed by upper endoscopy including duodenal biopsies. However, ileal microsporidiosis was also

Histoplasma capsulatum is a dimorphic fungus that can cause ileitis. In the disseminated form of histoplasmosis, the terminal ileum is commonly affected due to dissemination of the fungus, via the reticuloendothelial system, by macrophages that accumulate in lymphoid aggregates and Peyer’s patches [42]. In these patients, retrograde ileoscopy may lead to the diagnosis, demonstrating lesions ranging from segmental or continuous superficial mucosal ulcerations with erythema or edema to deep ulcers, with or without frank perforation [43]. Anisakis simplex is a nematode acquired by humans after the ingestion of raw fish infected with third-stage larvae. The infestation may involve the ileocecal region [29]. Since no specific therapy is available, prompt endoscopic removal of the parasite is the only approach, before it penetrates the small-bowel mucosa, causing a vigorous eosinophilic granulomatous response. Anisakis is generally removed during upper endoscopy (Fig. 7.1a, b) [44], but capsule endoscopy has also demonstrated enteric anisakiasis

7

Ileoscopy in the Diagnosis of Infectious Diseases

[45]. A case report by Trecca et al. [46] provided a detailed description of ascariasis detection by magnified ileoscopy. A worm emerging from the ileal mucosa was captured during biopsy of an enlarged submucosal follicle in a patient referred for severe weight loss and asthenia (Fig. 7.2a, b).

7.6

Conclusions

Endoscopic examination of the terminal ileum may play an important role in the diagnosis of infectious disease affecting the ileocecal region (Figs. 7.3a, b and 7.4a–c). This is of particular relevance in patients with suspected intestinal tuberculosis but is mandatory when the differential diagnosis includes Crohn’s disease. Moreover, in immunocompromised patients with HIV infection and diarrhea, ileoscopy may help in the diagnosis of several opportunistic infections of the terminal ileum, especially microsporidiosis, which can be successfully treated. Finally, the substantial diagnostic yield of ileoscopy in the presence of a clinical picture of acute ileitis should be taken into account in the decision-making process.

References 1. Zwas FR, Bonheim NA, Berken CA et al (1995) Diagnostic yield of routine ileoscopy. Am J Gastroenterol 90:1441–1443 2. Cherian S, Singh P (2004) Is routine ileoscopy useful? An observational study of procedure times, diagnostic yield, and learning curve. Am J Gastroenterol 99:2324–2329 3. Kundrotas LW, Clement DJ, Kubik CM et al (1994) A prospective evaluation of successful terminal ileum intubation during routine colonoscopy. Gastrointest Endosc 40:544–546 4. Geboes K, Ectors N, D’Haens G et al (1998) Is ileoscopy with biopsy worthwhile in patients presenting with symptoms of inflammatory bowel disease. Am J Gastroenterol 93:201–206 5. Mielants H, Veys EM, Cuvelier C et al (1988) Ilecolonoscopic findings in seronegative spondylarthropathies. Br J Rheumatol 27:95–105 6. Misra SP, Dwivedi M, Misra V (2006) Ileoscopy in 39 hematochezia patients with normal colonoscopy. World J Gastroenterol 12:3101–3104 7. Gillin JS, Urmacher C, West R et al (1983) Disseminated Mycobacterium avium-intracellulare infection in acquired immunodeficiency mimicking Whipple’s disease. Gastroenterology 85:1187–1191

45 8. Morini S, Lorenzetti R, Stella F et al (2003) Retrograde ileoscopy in chronic nonbloody diarrhea: a prospective case control study. Am J Gastroenterol 98:1512–1515 9. Corbett EL, Watt CJ, Walker N et al (2003) The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med 163:1009–1021 10. Horvath KD, Whelan RL (1998) Intestinal tuberculosis: return of an old disease. Am J Gastroenterol 93:692–696 11. Bhargava DK, Tandon HD, Chawla TC et al (1985) Diagnosis of ileocecal and colonic tuberculosis by colonoscopy. Gastrointest Endosc 31:68–70 12. Shah S, Thomas V, Mathan M et al (1992) Colonoscopic study of 50 patients with colonic tuberculosis. Gut 33:347–351 13. Bhargava DK, Kushwaha AKS, Dasarathy S et al (1992) Endoscopic diagnosis of segmental colonic tuberculosis. Gastrointest Endosc 38:571–574 14. Singh V, Kumar P, Kamal J et al (1996) Clinicocolonoscopic profile of colonic tuberculosis. Am J Gastroenterol 91:565–568 15. Misra SP, Misra V, Dwivedi M et al (1999) Colonic tuberculosis: clinical features, endoscopic appearance and management. J Gastroenterol Hepatol 14:723–729 16. Sato S, Yao K, Yao T et al (2004) Colonoscopy in the diagnosis of intestinal tuberculosis in asymptomatic patients. Gastrointest Endosc 59:362–368 17. Marshall JB (1993) Tuberculosis of the gastrointestinal tract and peritoneum. Am J Gastroenterol 88:989–999 18. Misra SP, Misra V, Dwivedi M (2007) Ileoscopy in patients with ileocolonic tuberculosis. World J Gastroenterol 13(11):1723–1727 19. Leung VK, Tang WL, Cheung CH et al (2001) Importance of ileoscopy during colonoscopy for the early diagnosis of ileal tuberculosis: report of two cases. Gastrointest Endosc 53:813–815 20. Misra SP, Misra V, Dwivedi M et al (1998) Colonic tuberculosis mimicking ulcerative colitis. J Assoc Physicians India 46:309–310 21. Cello JP (2004) Capsule endoscopy features of human immunodeficiency virus and geographical diseases. Gastrointest Endosc Clin N Am 14:169–177 22. Misra SP, Dwivedi M, Misra V et al (2004) Endoscopic biopsies from normal-appearing terminal ileum and cecum in patients with suspected colonic tuberculosis. Endoscopy 36:612–616 23. Epstein D, Watermeyer G, Kirsch R (2007) Review article: the diagnosis and management of Crohn’s disease in populations with high-risk rates for tuberculosis. Aliment Pharmacol Ther 25:1373–1388 24. Ouyang Q, Tandon R, Goh KL et al (2005) The emergence of inflammatory bowel disease in the Asian Pacific region. Curr Opin Gastroenterol 4:408–413 25. Lee YJ, Yang SK, Byeon JS et al (2006) Analysis of colonoscopic findings in the differential diagnosis between intestinal tuberculosis and Crohn’s disease. Endoscopy 38:592–597 26. Amarapurkar DN, Patel ND, Rane PS (2008) Diagnosis of Crohn’s disease in India where tuberculosis is widely prevalent. World J Gastroenterol 14:741–746 27. Almadi MA, Ghosh S, Aljebreen AM (2009) Differentiating intestinal tuberculosis from Crohn’s disease: a diagnostic challenge. Am J Gastroenterol 104:1003–1012

46 28. Garrido E, Sanroman AL, Rodriguez-Gandia MA et al (2009) Optimized protocol for diagnosis of acute ileitis. Clin Gastroenterol Hepatol 7:1183–1188 29. Di Lauro S, Crum-Cianflone NF (2010) Ileitis: when it is not Crohn’s disease. Curr Gastroenterol Rep 12:249–258 30. Matsumoto T, Iida M, Matsui T et al (1990) Endoscopic findings in Yersinia enterocolitica enterocolitis. Gastrointest Endosc 36:583–587 31. Sun HY, Chen MY, Wu MS et al (2005) Endoscopic appearance of GI mycobacterosis caused by the Mycobacterium avium complex in a patient with AIDS: case report and review. Gastrointestinal Endosc 61:775–779 32. Schneebaum CW, Novick DM, Chabon AB et al (1987) Terminal ileitis associated with Mycobacterium avium intracellulare infection in a homosexual man with acquired immune deficiency syndrome. Gastroenterology 92: 1127–1132 33. Cappell MS, Gupta A (1992) Gastrointestinal hemorrhage due to gastrointestinal Mycobacterium avium intracellulare or esophageal candidiasis in patients with the acquired immunodeficiency syndrome. Am J Gastroenterol 87:224–229 34. Morini S, Hassan C, Lorenzetti R et al (2004) Submucosal nodules containing purulent fluid: a colonoscopic sign of actinomycosis? Gastrointest Endosc 59:319–321 35. Cintron JR, Del Pino A, Duarte B et al (1996) Abdominal actinomycosis. Dis Colon Rectum 39:105–108 36. Committee AGAPC (1996) AGA technical review: malnutrition and cachexia, chronic diarrhea, and hepatobiliary disease in patients with human immunodeficiency virus infection. Gastroenterology 111:1722–1752

R. Lorenzetti et al. 37. Bini EJ, Cohen J (1998) Diagnostic yield and costeffectiveness of endoscopy in chronic human immunodeficiency virus-related diarrhea. Gastrointest Endosc 48: 354–361 38. Oldfield EC 3rd (2002) Evaluation of chronic diarrhea in patients with human immunodeficiency virus infection. Rev Gastroenterol Disord 2:176–178 39. Kearney DJ, Steuerwald M, Koch J et al (1999) A prospective study of endoscopy in HIV-associated diarrhea. Am J Gastroenterol 94:596–602 40. Michiels JF, Hofman P, Saint Paul MC et al (1993) Pathologic features of intestinal microsporidiosis in HIV positive patients. A report of 13 new cases. Pathol Res Pract 189:377–383 41. Shah RJ, Fenoglio-Preiser C, Bleau BL et al (2001) Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea. Am J Gastroenterol 96:1091–1095 42. Kahi CJ, Wheat LJ, Allen SD et al (2005) Gastrointestinal histoplasmosis. Am J Gastroenterol 100:220–231 43. Cappell MS, Mandell W, Grimes MM et al (1988) Gastrointestinal histoplasmosis. Dig Dis Sci 33:353–360 44. Zullo A, Hassan C, Scaccianoce G et al (2010) Gastric anisakiasis: do not forget the clinical history! J Gastrointest Liver Dis 19:359 45. Nakaji K (2009) Enteric anisakiasis which improved with conservative treatment. Inter Med 48:573 46. Trecca A, Gaj F, Serafini S et al (2005) Ileal ascariasis detected by magnified terminal ileoscopy. Endoscopy 37:1162

8

Results of Ileoscopy in Pediatric Patients Paola De Angelis, Erminia Romeo, Filippo Torroni, and Luigi Dall’Oglio

8.1

Traditional Ileoscopy

Ileoscopy is considered one of the most important diagnostic procedures, even in pediatric patients presenting with abdominal pain, obscure bleeding, chronic diarrhea, and suspicion of inflammatory bowel disease (IBD). The practice of pediatric colonoscopy and ileoscopy has evolved and improved over the past 20 years, both in terms of technique and technological advances [1]. It has become an important component of a complete traditional colonoscopy, with the ability to explore the cecal region and the small bowel and to perform multiple biopsies of the terminal ileum. Data from retrospective studies assessing the diagnostic value of terminal ileum biopsies suggest that they are mainly helpful in patients with inflammatory diarrhea and/or suspected IBD [2]. Despite the fact that the distal 15–40 cm of the terminal ileum is not always displayed, routine endoscopy of the terminal ileum is, nonetheless, suggested in all patients with established IBD and/or persistent diarrhea, lower gastrointestinal tract bleeding, severe irritable bowel syndrome, or suspected neoplastic disease [3]. Correct indications for terminal ileoscopy in pediatric patients are the suspicion of inflammatory (IBD, allergic enterocolitis, and autoimmune enteropathy), infectious (Yersinia, tuberculosis), congenital (chronic

P. De Angelis (&) Digestive Surgery and Endoscopy Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy e-mail: [email protected]

granulomatous disease, glycogen storage disease types 1b and 1c, defective neutrophil chemotaxis) and neoplastic (lymphoma) diseases, for which the histology of biopsied specimens is essential to complete the diagnosis. The correlation between endoscopic and histologic findings is high, but accurate microscopic and electronic study of biopsies of normal ileum must be included, especially in patients with abdominal pain and/or chronic diarrhea, to establish the presence of alterations and confirm the diagnosis [4]. The clinical results of ileoscopy in the diagnosis of IBD are excellent and the role of histology is crucial to reach a diagnosis, together with clinical data and other examinations. Endoscopy contributes to establishing the best diagnostic definition of type, location, extent, and severity of disease, to beginning or adjusting medical therapy, and to performing endoscopic dilation through a guide wire under radiologic monitoring. Examination of the entire colon with intubation of the distal ileum provides the best chance of reaching a diagnosis; it can detect evidence of Crohn’s disease and thus help to distinguish between IBD and lymphoid nodular hyperplasia, which is very common in children [1]. The utility of repeat endoscopy for the management of pediatric IBD is that it can be used to evaluate the effects of medical treatment, since mucosal healing is an important endpoint [5]. Despite several diagnostic investigations available to perform the complex diagnosis of IBD, colonoscopy with ileoscopy remains the gold-standard, also in children. Colonoscopy and ileoscopy with ileal biopsies combined with upper endoscopy achieve the highest diagnostic yields in the diagnosis of gastrointestinal graft-versus-host-disease (GVHD) [6]. The endoscope is an essential tool also in assessing the intestinal

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allograft after intestinal transplantation. In these patients, frequent postoperative surveillance ileoscopies with biopsies are highly recommended [7]. Magnified ileoscopy with histological examination of macroscopic mucosal abnormalities facilitates the recognition of strongly suspected mucosal villous subtotal or total atrophy [8]. This diagnostic opportunity should be strongly considered in pediatric patients due to the high frequency of celiac disease without typical symptoms in children and adolescents. Colonoscopy and retrograde ileoscopy are routinely performed in many pediatric centers but the success of the procedure in terms of quality, extent, and duration depends on many factors [9]. Visualization of the intestinal mucosa, completion of the examination with optimal detection of pathological lesions, and therapeutic maneuvers are a function of the quality of bowel preparation. While there is no ideal preparation, several agents with different palatability and several protocols (e.g., sodium phosphate and stimulant laxative based protocols), both aimed at improving compliance in children, are available [10, 11]. Extreme care should be taken in performing a complete colonoscopy and ileoscopy in children with a known or suspected diagnosis of severe ulcerative disease or Crohn’s colitis, due to the high risk of perforation and hemorrhage [1]. For pediatric endoscopy, the technical rules to perform colonoscopy until the ileum are the same as in adults, involving the same general principles, patient positioning, loop formation, manual compression, withdrawal of the instrument, etc., but greater caution is required, regardless of the endoscope used (pediatric colonoscope or adult instrument down to 3 years or 15 kg). Training in pediatric traditional ileoscopy must include not only technical knowledge of endoscopy but also gastroenterology and a background in pediatrics, which is useful in approaching children with digestive disease and their families especially when further diagnostic steps and therapeutic measures must be proposed.

8.2

Capsule Endoscopy and SmallBowel Enteroscopy

The small bowel remains the last frontier in terms of endoscopic visualization, as it is beyond the length of current endoscopes. The use of enteroscopy, or small-

Fig. 8.1 Capsule delivery device

bowel endoscopy, has been limited in the pediatric age group. Currently, intraoperative enteroscopy is the only method to investigate the small bowel, including in children, but it requires abdominal laparotomy or laparoscopy and thus has a limited use in pediatrics. The recent development of a swallowable, wireless capsule endoscope provides the unique opportunity to non-invasively visualize the entire small bowel. Studies in adult patients have demonstrated that the disposable capsule is innocuous and highly effective [12]. Given Imaging’s capsule endoscopy consists of a disposable plastic capsule (Pillcam SB) weighing 3.7 g and measuring 11 mm in diameter and 26 mm in length. It contains a battery-powered flashing light source, the capsule chip camera sensor, and a micro transmitter that allows the acquisition of high-quality images of the bowel and their transmission via digital radiofrequency. The battery permits an average total recording time of approximately 8 h, generating over 100,000 images. The disposable capsule is then eliminated in the stool and discarded. A limitation of wireless capsule endoscopy (WCE) in children is the size of the capsule, which precludes its use in infants and very young children [13, 14]. In children unable to swallow the capsule, it can be positioned endoscopically through specific devices (Fig. 8.1). The Pillcam SB has been approved by the

8

Results of Ileoscopy in Pediatric Patients

US Food & Drug Administration for visualization of the small-bowel mucosa in adults and in children age 10 years and older. However, there is clinical experience regarding its use in children as young as 3 years of age, after endoscopic placement. The most common indications for WCE are: • Obscure gastrointestinal bleeding, including irondeficiency anemia • Suspected Crohn’s disease • Suspected small intestinal tumors and surveillance in patients with polyposis syndrome (Peutz-Jeghers, juvenile polyposis) • Suspected or refractory malabsorption syndrome (celiac disease, intestinal lymphangiectasia, proteinlosing enteropathies, etc.). Other indications are: • Food allergy or eosinophilic enteropathies • Drug-induced mucosal injury • Chronic abdominal pain with high suspicion of small-bowel pathology • Transplantation (rejection of intestinal graft, GVHD in bone-marrow transplant recipients). Contraindications include: • Known or suspected gastrointestinal obstruction, strictures • A cardiac pacemaker or other implanted electromedical devices [15]. The risk of retention in an adult is 0.75%. There has been one report in the pediatric field of a delay in elimination of the capsule, which resolved after the administration of corticosteroids [16]. Two further reports described capsule retention requiring urgent surgical intervention due to acute intestinal obstruction (vomiting and abdominal pain) in patients with Crohn’s disease who were radiologically negative for small-bowel stenosis [17]. The experience of the Digestive Surgery and Endoscopy Unit of Ospedale Pediatrico Bambino Gesù, (IRCCS, Rome), acquired over the last 5 years, consists of 207 WCE procedures performed in 207 patients (age range: 18 months–25 years; smallest body weight: 8 kg). One patient with Crohn’s disease experienced capsule retention, resolved by the administration of corticosteroids. In two patients (one with insulin-dependent diabetes mellitus), the capsule did not pass the stomach following 8 h of procedure (eliminated 36 h later). In one patient, the capsule impacted in the esophagus due to peptic stenosis and it was urgently removed.

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Fig. 8.2 Medium ileum: large polyp

The immediate future in the pediatric field will be the combination of WCE and a companion therapeutic procedure, such as double-/mono-balloon enteroscopy. In adult patients, the diagnostic and therapeutic possibilities of small-intestinal disease drastically improved with the advent of doubleballoon enteroscopy (DBE). This allowed biopsy samples to be acquired and therapeutic procedures (polypectomies, hemostasis, dilations) to be successfully performed [18]. The small bowel has always been a difficult area to explore. DBE was introduced at the beginning of 2001 for small-bowel studies, by Yamamoto et al. [19]. This procedure is now available for routine clinical use in adults. The largest reported pediatrics experience was published in 2007 by Leung, who described 30 DBE procedures in 24 pediatric patients [20]. Recently, a novel single balloon enteroscopy (SBE) system was developed to examine the small intestine. The procedure is simpler than DBE and is indicated for suspected gastrointestinal bleeding, Crohn’s disease, abdominal pain, intestinal polyposis, and suspected intestinal tumor (Figs. 8.2, 8.3 and 8.4). The use of SBE in children is well known, including in newborns and infants [21]. The SBE system (Olympus XSIF-Q 260Y) has a working length of 200 cm, an outer diameter of 9.2 mm, a working channel of 2.8 mm and a soft overtube (Olympus XST SB1) with a distal silicon balloon loaded onto the endoscope, and a pressure-controlled pump (Olympus XMAJ 1725), which is used to inflate the overtube balloon.

50

P. De Angelis et al.

Rare complications following SBE in a large adult series of 166 procedures consisted of one perforation, which occurred after dilation of a benign stricture, whereas no serious complications have thus far been reported in pediatric patients [23]. Thus, in general, SBE appears to be a safe and effective method for the detection of small-bowel pathology. Contraindications to the procedure include previous abdominal surgery. Pediatric gastroenterologists should be appropriately and specifically trained in this procedure.

8.3 Fig. 8.3 Single-balloon enteroscopy: polypectomy

Fig. 8.4 Single-balloon enteroscopy: jejunal mass

Working together, an endoscopist, his or her assistant, and an anesthesiologist generally perform SBE with the aid of fluoroscopy and the patient under general anesthesia. The patient’s position is left lateral for the oral approach and prone for the anal route; however, in the pediatric population, the anal approach is technically more complex due to the risk of overrun of the colon and passage through the ileocecal valve. The most appropriate approach should be decided according to the position of the lesions previously found on WCE. Enteroscopy combined with WCE provides excellent diagnostic and therapeutic yields during polypectomy for intestinal polyps, dilation of stenosis in Crohn’s disease, biopsies in suspected tumor lesions, and hemostasis of bleeding lesions of the small bowel [22].

Intraoperative Ileoscopy and Indications for Surgery in Small-Bowel Diseases

The most frequent indications in which a combined endoscopic and surgical approach is indicated or mandatory are: • To allow endoscope progression • To perform endoscopic operative procedures in high-risk patients and situations • Coagulopathies • Large-pedicle ([1 cm) polyps • Underweight children • Portal hypertension • In patients with large venous malformations. In some patients, it may be impossible to progress to the medium and distal ileum, despite the use of modern enteroscopes. While modern endoscopic accessories have enabled more procedures than ever before, in children, the need for surgical support, either traditional or laparoscopic, in exploration of the small bowel is more frequent than in adults. This is due to the thinness of the jejunal and ileal walls, with a high risk of perforation in polypectomy, mucosectomy, or the treatment of vascular malformations.

8.4

Surgically Assisted Ileoscopy

Through a laparotomy, the surgeon can easily control the tip of the endoscope, inserted above the ligament of Treitz. The endoscopist pushes the scope while the surgeon essentially invaginates the bowel on the scope, thus allowing the endoscope to reach the distal ileus. In case of lesions that should be endoscopically treated, the surgeon uses a dermographic pen to mark the correct site to be treated following the withdrawal

8

Results of Ileoscopy in Pediatric Patients

of the endoscope. This strategy is very important in order to avoid traction or manipulations at the polypectomy site or banding of a vascular malformation, such as blue rubber bleb nevus syndrome [24]. In these patients, who have frequent and sometimes massive bleeding, the only treatment is a combination of wedge resection, polypectomy, suture-ligation, segmental bowel resection, and band ligation, all of which are possible and safe with a surgically assisted endoscopic approach. After therapeutic endoscopy, the surgeon can correctly verify the procedure’s effectiveness and the absence of complications, such as a burn or perforation. In the latter, the treatment of choice involves the use of resorbable suture, with suturing preferably restricted to the serosal layer. Although endoscopic progression is easier with the open technique, the well-trained pediatric surgeon can perform all of the above-mentioned procedures using laparoscopy. In some cases, it is possible to grasp the affected intestinal segment and extract it through the enlarged trocar site, to perform a resection or other procedures. The most important and frequent pediatric indications for ileal surgery are: • Jejunostomy in patients with a history of abdominal surgery • Ileal strictures • Ileal tumors • Large venous malformations. It is important to note not only the indications for ileal surgery but also the role of surgery, either laparoscopic or traditional, depending on the surgeon’s experience, with respect to the possibility of endoscopic treatment. However, in patients with previous surgery, an endoscopic jejunostomy could be hazardous because of adhesions and possible bowel overlap, with the risk of intestinal fistulas. In such cases, a surgical approach, even if endoscopically supported, is the safest strategy. In patients with Crohn’s disease and ileal strictures longer than 10 cm, and especially strictures not easily reached by the endoscope, surgery is used to perform a resection and anastomosis or a strictureplasty [25]. Dissection of the affected bowel is often very difficult due to adhesions and mesentery thickening, which complicate retraction. In case of ileal tumors, which are rare in the pediatric population, endoscopy plays a role only in the early diagnosis of superficial lesions suitable for

51

mucosectomy. Due to the non-specific symptomatology, a late diagnosis generally indicates the need for a surgical approach to these patients.

References 1. Thompson M, Murphy MS (2006) Diagnostic colonoscopy. In: Winter HS et al (eds) Pediatric gastrointestinal endoscopy, textbook and atlas. BC Decker, Hamilton 2. Geboes K (2007) The strategy for biopsies of the terminal ileum should be evidence based. Am J Gastroenterol 102(5):1090–1092 3. Börsch G, Schmidt G (1985) Endoscopy of the terminal ileum. Diagnostic yield in 400 consecutive examinations. Dis Colon Rectum 28(7):499–501 4. Melo MM, Cury PM, Ronchi LS et al (2009) Terminal ileum of patients who underwent colonoscopy: endoscopic, histologic and clinical aspects. Arq Gastroenterol 46(2):102–106 5. Thakkar K, Lucia CJ, Ferry GD et al (2009) Repeat endoscopy affects patient management in pediatric inflammatory bowel disease. Am J Gastroenterol 104(3): 722–727 6. Thompson B, Salzman D, Steinhauer J et al (2006) Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant 38(5): 371–376 7. Sigurdsson L, Reyes J, Putnam PE et al (1998) Endoscopies in pediatric small intestinal transplant recipients: five years experience. Am J Gastroenterol 93(2):207–211 8. Trecca A, Gaj F, Gagliardi G et al (2009) Role of magnified ileoscopy in the diagnosis of cases of coeliac disease with predominant abdominal symptoms. Scand J Gastroenterol 44(3):320–324 9. Israel DM, McLain BI, Hasall E (1994) Successful pancolonoscopy and ileoscopy in children. J Pediatr Gastr Nutr 19(3):283–289 10. Hunter A, Mamula P (2010) Bowel preparation for pediatric colonoscopy procedures. J Pediatr Gastr Nutr 51:254–261 11. Turner D, Levine A, Weiss B et al (2010) Evidence-based recommendations for bowel cleansing before colonoscopy in children: a report from a national working group. Endoscopy 42:1063–1070 12. Gong F, Swain P, Mills T (2000) Wireless capsule endoscopy. Gastrointest Endoscopy 51(6):725–729 13. Barth BA, Donovan K, Fox VL (2004) Endoscopic placement of the capsule endoscope in children. Gastrointest Endosc 60(5):818–821 14. de’ Angelis GL, Fornaroli F, de’ Angelis N et al (2007) Wireless capsule endoscopy for pediatric small bowel disease. Am J Gastroenterol 102:1749–1757 15. Seidman E, Sant’Anna AM, Dirks MH (2004) Potential application of WCE in the pediatric age group. Gastrointest Endosc Clin N Am 14:207–217 16. Sant’Anna AM, Doubois J, Miron MC et al (2005) Wireless capsule for obscure small bowel disorder: final results of

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19.

20. 21.

P. De Angelis et al. the first pediatric controlled trial. Clin Gastroenterol Hepatol 3:264–270 Barkin J, Friedman S (2002) Wireless capsule endoscopy requiring surgical intervention. Am J Gastroenterol 97:A907 Chong A, Chin B, Meredith C (2006) Clinically significant small-bowel pathology identified by double-balloon enteroscopy but missed by capsule endoscopy. Gastrointest Endosc 64(3):445–449 Yamamoto H, Sekine Y, Sato Y et al (2001) Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 53:210–220 Leung YK (2007) Double balloon endoscopy in pediatric patients. Gastrointest Endosc 66(Suppl):S54–S56 Kramer RE, Brumbaugh DE, Soden JS, Capocelli KE, Hoffenberg EJ (2009) First successful anterograde singleballoon enteroscopy in a 3 year-old with occult GI bleeding. Gastrointest Endosc 70(3):546–549

22. Ramchandani M, Reddy DN, Gupta R et al (2009) Diagnostic yield and therapeutic impact of single-balloon enteroscopy: series of 106 cases. J Gastroenterol Hepatol 24:1631–1638 23. Aktas H, de Ridder L, Haringsma J et al (2010) Complications of single-balloon enteroscopy: a prospective evaluation of 166 procedures. Endoscopy 42(5):365–368 (Epub 2010, Feb 22) 24. Fishman SJ, Smithers CJ, Folkman J et al (2005) Blue rubber bleb nevus syndrome: surgical eradication of gastrointestinal bleeding. Ann Surg 241(3):523–528 25. Wibmer AG, Kroesen AJ, Gröne J et al (2010) Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn’s disease review of the literature. Int J Colorectal Dis 25:1149–1157

9

The Role of Histology in Small Bowel Diseases Vincenzo Villanacci and Gabrio Bassotti

9.1

Introduction

The role of histology in the diagnosis of different pathologies of the terminal ileum and cecal region (TICR) is one of the most difficult aspects of surgical pathology for two important reasons: (1) the site of the TICR, and thus the dependence on the ability of the endoscopist to obtain an adequate number of specimens and a correct orientation of the biopsy samples, and (2) the complexity of the pathological conditions involving this site. Therefore, to achieve a correct diagnosis, good working relationships between gastroenterologists, radiologists, endoscopists, and pathologists are of paramount importance, together with a correct methodological approach. In this chapter, we begin with a consideration of the normal histological aspect of the TICR and then continue with a discussion of the different pathological conditions, which can be summarized as follows: • Crohn’s disease • Backwash ileitis and pouchitis • Inflammatory conditions • Ischemia • Celiac disease • Rare pathological entities • Tumors.

V. Villanacci (&) Department of Pathology, Spedali Civili, University of Brescia, Brescia, Italy e-mail: [email protected]

Under normal conditions, and especially on biopsy material, in which it is possible to observe only the mucosa, muscularis mucosae, and superficial part of the submucosa, the pathologist should pay particular attention to the following elements: 1. The morphology and the architecture of the villi. Normally, the villous/crypts ratio is not \ 3:1. 2. Intraepithelial lymphocytes (IEL). Generally, these are T lymphocytes, CD3+ and CD8+; the normal number of IEL is not [25/100 epithelial cells [1]. 3. Inflammatory cells in the lamina propria. Apart from the crypts, these cells, and particularly eosinophils, are usually present along with lymphoid follicles, strictly related to Peyer’s patches [2]. 4. The number of IEL in the cecal region. A value C30 IEL/100 epithelial cells is considered pathological. Of equal importance is the thickness of the subepithelial collagen layer, which should be examined for signs of microscopic (lymphocyticcollagen) colitis. 5. The presence of granulomas. Their presence indicates the need to include both Crohn’s disease and Yersinia infection in the differential diagnosis.

9.2

Inflammatory Bowel Disease

The first and most important pathological form of TICR is Crohn’s disease. Its best known and diagnostic hallmark is the presence of sarcoid-type granulomas that are Ziehl–Neelsen negative, although in most cases no granulomas are found. The differential diagnosis for granulomatous disease of the TICR must include Yersinia enterocolitica/pseudotubercularis and tuberculosis infections. In the absence of

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1_9,  Springer-Verlag Italia 2012

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Fig. 9.1 Crohn’s disease. a Biopsy of the terminal ileum (H&E, 49), b crypt abscess (H&E 209), c granulomas, d negative Ziehl Neelsen staining (c and d, 409)

granulomas, there are other important features to be evaluated that are indicative of Crohn’s disease (Fig. 9.1), in particular the architectural distortion of the crypts, crypt density, a discontinuous type of inflammatory infiltrate (especially basal plasmocytosis), and fissuring ulcerations, if present [3]. In patients with severe ulcerative colitis extending to all segments of the colon (pancolitis), it is sometimes possible to find an active inflammation in the distal few centimeters of the terminal ileum, presumably related to reflux of the colonic contents. This condition, referred to as ‘‘backwash ileitis,’’ can be difficult to distinguish from Crohn’s disease. In resection specimens, the differentiation is straightforward, because the continuity of the disease from the proximal colon into the ileum, with an incompetent ileocecal valve, can be readily appreciated. However, in small mucosal biopsies, the distinction between the two conditions is much more difficult; in fact, backwash ileitis can mimic active Crohn’s disease of the ileum. In this situation, the pathologist should be informed of the endoscopic features of the disease, notably its extent in the colon, its continuity between the colon and ileum, and the appearance of the ileocecal valve, as this information will avoid an erroneous diagnosis of

Crohn’s disease. In addition, an important point is the accurate morphological evaluation of the mucosa, in which it is possible to distinguish an inflammatory infiltrate rich in neutrophils and eosinophils from lymphoyd aggregates normal for the biopsy sites and few superficial erosions but with a normal architecture of the crypts and no fissuring ulcerations, granulomas, or transmural lymphoid aggregates [4, 5]. In patients treated for ulcerative colitis by total colectomy and creation of a continent ileo-anal anastomosis, there may be inflammation of the ileal pouch. In many centers, scoring systems have been used to grade the extent of the histopathological abnormalities. The amount of ulceration and acute inflammation is usually assessed according to the St. Mark’s scoring system, in which an acute inflammatory score C4 usually implies pouchitis. It should be noted that only the acute inflammatory score correlates well with the clinical and endoscopic features of pouchitis [6, 7]. Concerning dysplasia in the pouch mucosa, a study by Heuschen et al. [8] showed a strong association of backwash ileitis with the development of colorectal cancer in patients with ulcerative colitis who underwent proctocolectomy. In patients with

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The Role of Histology in Small Bowel Diseases

55

Fig. 9.2 a, b Histological (H&E staining) examination of ischemic colitis, shown at 109 and 209 magnification, respectively. c, d Histological (H&E staining) examination of actinic colitis, with fibrosis and typical hyaline dilated vessels, shown at 209 and 109, respectively

pancolitis, colorectal cancer was found in 29% of the 107 patients with backwash ileitis compared to 9% of the patients without and 1.8% of the patients with limited left-sided colitis. However, discrete pathological criteria for backwash ileitis were not defined. In view of the reports of dysplasia and carcinoma in the pouch mucosa and in the columnar cuff, some form of surveillance of the ileal reservoirs is recommended. Importantly, biopsies should be taken from several different sites in the pouch, according to standardized methodology, due to the evolving histological changes in the colonic phenotypic and thus the patchy inflammation of the pouch mucosa [9, 10].

9.3

Ischemia–Actinic Ileocolitis

Ischemia in the TICR displays the typical features of coagulative necrosis. In so-called actinic ileitis, there is a previous history of radiotherapy. Morphologically, the features of the disease include fibrosis in the lamina propria, bizarre radiation fibroblasts more frequent in the submucosa, and telangiectatic mucosal blood vessels. Indeed, telangiectatic mucosal blood vessels may be a prominent feature of this condition and are often the only diagnostic feature seen in a small biopsy

(Fig. 9.2). The thick hyaline walls of the vessels will distinguish them from the thin-walled angioma-like dilated vessels of angiodysplasia [11, 12].

9.4

Celiac Disease

Particular attention must be paid to the possible diagnosis of celiac disease during evaluation of the TICR. At present, the gold standard for the diagnosis of celiac disease is the histological evaluation of duodenal biopsies, with the assumption that the most frequent and most severe lesions are present in the proximal part of the small intestine [13, 14]. However, an important problem is the correct identification of the early lesions, in particular type 1 and 2, as scored using the Marsh–Oberhuber classification [15, 16], corresponding to grade A of the newly proposed classification [17]. Recognition of the early lesions in celiac disease is one of the major pitfalls in its histological diagnosis, as the only morphological alteration in the presence of normal villi is a pathological increase of IEL [18–21]. However, as recently stressed by Rostami ‘‘…most European pathologists (and not only European) do not routinely count the intraepithelial lymphocytes in duodenal biopsies. Minor intestinal changes compatible with [celiac disease] are, therefore, overlooked in

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V. Villanacci and G. Bassotti

Fig. 9.3 Celiac disease. The low atrophy of the villi in the terminal ileum are shown in this H&E-stained histological sample at a 109 and b 209 magnification. A pathological increase in T lymphocytes can be seen with immunostaining for CD3 at c 109 and d 209 magnification

many symptomatic cases and subsequently labeled as [inflammatory bowel syndrome] or functional’’ [22]. In the TICR, the clinician is confronted with a similar problem, the difference being that the alterations are more infrequent and in some cases are confused with those of the other, above-described pathologies. In an early study by Dickey and Hughes [23], biopsies taken from the terminal ileum during colonoscopy/ileoscopy were examined for features of gluten-sensitive enteropathy. The authors studied 30 patients with duodenal villous atrophy consistent with celiac disease and 60 controls with no evidence of the disease or of inflammatory bowel disease. The results demonstrated that only one patient, in the celiac disease group, had partial villous atrophy with crypt hyperplasia in the terminal ileum. IEL counts were significantly higher in the celiac group than in controls. An ileal IEL count C25 IEL/100 enterocytes had a sensitivity for duodenal villous atrophy of 60% and a specificity of 100%. Similar results were obtained by Hopper et al. [24], who investigated 20 patients newly diagnosed with celiac disease and four control groups: celiac disease on gluten-free diet, inflammatory bowel disease, chronic

diarrhea, and polyp surveillance. The results showed that the IEL count in the terminal ileum was significantly higher in patients with celiac disease than in the control groups, and that IEL count as a test for this disease using a cut-off of[25 IEL/100 enterocytes had a sensitivity of 45% and a specificity of 97%. Thus, these two studies underline the fact that celiac disease may involve the entire small bowel. An increased IEL density in the TICR is associated with duodenal villous atrophy and should prompt a search for celiac disease by serology and duodenal biopsy. Conversely, a normal IEL count does not allow the exclusion of celiac disease with confidence; for this reason, quantifying IELs in terminal ileum biopsies may be of limited clinical/pathological value. However, the subjective recognition of IEL on a terminal ileum biopsy should alert the referring clinician to the possibility of underlying celiac disease. The same caveat can be made in cases of so-called lymphocytic gastritis, in which a possible association with celiac disease is present in 38% of the cases, and in so-called lymphocytic colitis, which may be indicative of the presence of celiac disease (Fig. 9.3) [25, 26].

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The Role of Histology in Small Bowel Diseases

57

Fig. 9.4 Vasculitis with infiltration of inflammatory cells in the vessel walls, as seen in this H&E stained histological sample at a 409 and b 29 magnification. Angiodysplasia with typical dilated vessels in the submucosa in this H&E stained sample shown at c 109 and d 409 magnification

The take-home message is the importance of a correct evaluation of the morphological features. The pathologist must be able to provide the clinician with a precise description of the small-bowel mucosa in order to allow an accurate diagnosis.

9.5

Rare Pathological Entities

Among the rare pathological entities involving the TICR, two conditions in particular should be noted: angiodysplasia and vasculitis. Angiodysplasia is related to an abnormal proliferation, congenital or acquired, of small vessels prevalent in the submucosa. More difficult to diagnose on biopsy material is the second condition, vasculitis. In fact, the diagnosis, apart from the epiphenomenon of ischemia in the mucosa, is possible only on total thickness biopsies or surgical specimens (Fig. 9.4) [27, 28].

9.6

Tumors

Tumors in the TICR are rare but include precancerous lesions and epithelial tumors, endocrine tumors, gastrointestinal stromal tumors (GISTs), and lymphomas. As for the other pathological conditions discussed herein, their diagnosis is based on a correct histopathological evaluation [27, 28].

References 1. Hayat M, Cairns A, Dixon MF, O’Mahony S (2002) Quantitation of intraepithelial lymphocytes in human duodenum: what is normal? J Clin Pathol 55:393–394 2. Cuvelier C, Demetter P, Mielants H, Veys EM, De Vos M (2001) Interpretation of ileal biopsies: morphologic features in normal and diseased mucosa. Histopathology 38:1–12

58 3. Stange EF, Travis SP, Vermeire S, Beglinger C, Kupcinkas L, Geboes K, Barakauskiene A, Villanacci V, Von Herbay A, Warren BF, Gasche C, Tilg H, Schreiber SW, Scholmerich J, Rinisch W (2006) European Crohn’s and Colitis Organisation. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut 55(Suppl 1):i1–i15 4. Gustavsson S, Weiland LH, Kelly KA (1987) Relationship of backwash ileitis to ileal pouchitis after ileal pouch-anal anastomosis. Dis Col Rectum 30:25–28 5. Warren BF, Sheperd NA (2001) What are the controversies in histopathological diagnosis? In: DP, Warrren BF, Mortensen NJ (eds) Challenges in inflammatory bowel disease. Blackwell Science, London 6. Moskowitz RL, Sheperd NA, Nicholls RJ (1986) An assessment of inflammation in the reservoir after restorative proctocolectomy with ileoanal ileal reservoir. Int J Colorectal Dis 1:167–174 7. Sheperd NA, Hulten L, Tytgat GN, Nicholls RJ, Nasmyth DG, Hill MJ, Fernandez F, Gertner DJ, Rampton DS (1989) Pouchitis. Int J Colorectal Dis 4:205–229 8. Heuschen UA, Hinz U, Allemeyer EH, Stern J, Lucas M, Autschbach F, Herfarth C, Heuschen C (2001) Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis. Gastroenterology 120:841–847 9. Sheperd NA, Healey CJ, Warren BF, Richman PI, Thomson WHF, Wilkinson SP (1993) Distribution of mucosal pathology and an assessment of colonic phenotypic change in the pelvic ileal reservoir. Gut 34:101–105 10. Setti-Carraro P, Talbot IC, Nicholls RJ (1994) Long term appraisal of the histological appearances of the ileal mucosa after restorative proctocolectomy for ulcerative colitis. Gut 35:1721–1727 11. Talbot IC, Price AB (1987) Biopsy pathology in Colorectal Disease. Chapman and Hall, London 12. Montgomery EA (2006) Biopsy interpretation of the gastrointestinal tract mucosa. Lippincott Williams & Wilkins, Philadelphia 13. Green PH, Jabri B (2003) Coeliac disease. Lancet 362:383–391 14. Ravelli A, Bolognini S, Gambarotti M, Villanacci V (2005) Variability of histologic lesions in relation to biopsy site in

V. Villanacci and G. Bassotti

15.

16.

17.

18.

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21.

22. 23. 24.

25.

26.

27. 28.

gluten-sensitive enteropathy. Am J Gastroenterol 100: 177–185 Marsh MN (1990) Grains of truth: evolutionary changes in small intestinal mucosa in response to environmental antigen challenge. Gut 31:111–114 Oberhuber G, Granditsch G, Vogelsang H (1999) The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 11:1185–1194 Corazza GR, Villanacci V (2005) Coeliac disease. Some considerations on the histological classification. J Clin Pathol 58:573–574 Mahadeva S, Wyatt JI, Howdle PD (2002) Is a raised intraepithelial lymphocyte count with normal duodenal villous architecture clinically relevant? J Clin Pathol 55:424–428 Antonioli DA (2003) Celiac disease: a progress report. Mod Pathol 16:342–346 Kakar S, Nehra V, Murray JA, Dayharsh GA, Burgart LJ (2003) Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol 98:2027–2033 Jarvinen TT, Kaukinen K, Laurila K, Kyronpalo S, Rasmussen M, Maki M, Korhonen H, Reunala T, Collin P (2003) Intraepithelial lymphocytes in celiac disease. Am J Gastroenterol 98:1332–1337 Rostami K (2003) From microenteropathy to villous atrophy: what is treatable? Dig Liver Dis 35:758–789 Dickey W, Hughes DF (2004) Histology of the terminal ileum in coeliac disease. Scand J Gastroenterol 39:665–667 Hopper AD, Hurlstone DP, Leeds JS, McAlindon ME, Dube AK, Stephenson TJ, Samders DS (2006) The Occurrence of terminal ileal histological abnormalities in patients with coeliac disease. Dig Liver Dis 38(11):820–822 Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C (2004) Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut 53:536–541 Villanacci V, Bassotti G, Liserre B, Lanzini A, Lanzarotto F, Genta RM (2006) Helicobacter pylori infection in patients with celiac disease. Am J Gastroenterol 101(8):1880–1885 Greenson JK (ed) (2010) Diagnostic pathology: gastrointestinal, 1st edn. Amirsys Inc, Salt Lake City Fenoglio C (2008) Preiser gastrointestinal pathology. An atlas and text, 3rd edn. LWW, Philadelphia

Radiological Diagnosis of Small-Bowel Diseases

10

Laura Maria Minordi, Amorino Vecchioli, Luigi Larosa, and Lorenzo Bonomo

10.1

Introduction

The small bowel has been a subject of intense interest in radiology. Over the past several years, many techniques have been standardized and their applications verified for the diagnosis of a wide range of pathologies. Currently, these techniques include direct radiography, barium studies, ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI).

10.2

Direct Abdominal Radiography

Direct abdominal radiography is the first exam to be performed in patients with acute abdominal disease, especially when obstruction is suspected. Even if a specific correct interpretation is not always possible, radiography usually provides adequate information for the subsequent diagnostic approach [1].

10.3

low-density barium dose and a series of radiographs are subsequently acquired to follow barium progression to the ileocecal region. However, this method is burdened by a high rate of false negatives due to overlapping intestinal loops, which can mask even gross organic lesions [2]. The SBFT can be completed by a peroral pneumocolon (PP): when the barium has reached the right colon, air or CO2 is insufflated by the rectal route to obtain its reflux into the ileum. In a previous study [3], we demonstrated the superiority of PP over SBFT in the evaluation of patients with suspected Crohn’s disease.

Small-Bowel Follow-Through Study and Peroral Pneumocolon

At present, the most commonly used radiologic method is the small-bowel follow-through study (SBFT), in which the patient is administered a

L. M. Minordi (&) Department of Bio-Imaging and Radiological Sciences, Catholic University (UCSC) Radiology Institute, Rome, Italy e-mail: [email protected]

10.4

Enteroclysis

With the introduction of enteroclysis, all the disadvantages of the previously described techniques have been overcome. In enteroclysis, contrast media (barium and methylcellulose or air) are administered by naso-jejunal tube to obtain a double-contrast study of the small-bowel loops [4]. The disadvantages of the procedure are the need for intubation, patient discomfort during the intubation, and the higher radiation dose than in a conventional follow-through study. In patients with Crohn’s disease, the initial intestinal alterations are plical thickening and aphthous ulcerations [5]. The latter appear as superficial depressions, 1–2 mm in diameter, often surrounded by a halo. They may be the only radiologic abnormality or they may be associated with larger ulcers or more extended alterations that form a characteristic cobblestone pattern (Fig. 10.1). The association of aphthous ulcerations with plical thickening and granulomas confirms the early stage of the disease [5].

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10.5

Fig. 10.1 Enteroclysis shows a cobblestone pattern and stenosis of the last ileal loop (arrows)

Linear ulcers along the mesenteric margin are another important signs of Crohn’s disease. These ulcers can be over 15 cm long and typically develop parallel to the shortest concave or straight mesenteric margin. Deep ulcers cause luminal narrowing, resulting in concentric or asymmetrical stenosis. In addition, stenosis of small-bowel loops frequently occurs from the combination of fibrosis, mural thickening, and spasm. During contrast studies, true stenosis should be distinguished from narrowing caused by ulceration and spasm; however, in some cases this distinction can be very difficult [5]. Also, contrast studies show fistulous tracts in approximately 20–40% of patients with Crohn’s disease. In Crohn’s disease the choice between SBFT and enteroclysis should be made by the radiologist based on the clinical situation, while enteroclysis should be the first exam in patients with suspected small-bowel tumors [6]. Nonetheless, these radiological techniques provide only indirect information on the intestinal wall and adjacent extraintestinal structures (Fig. 10.2a) whereas US, CT (Fig. 10.2b) and MRI allow direct visualization of wall (thickness and structure) and the adjacent extraintestinal structures (mesentery, perivisceral fibrofatty cells, lymph nodes, peritoneal spaces).

Ultrasound Appearance of Crohn’s Disease and Malignancies

As a non-invasive procedure free of exposure to ionizing radiation or conventional radiologic contrast medium, US is ideal for use in patients with chronic inflammation, in children, and in some small-bowel disorders to prove or rule out a clinical suspicion. The tone and contractile activity of the small-bowel loops under physiologic conditions can be readily visualized on US. The most important ultrasound finding indicative of Crohn’s disease is the symmetrical mural thickening, with preserved stratification or diffuse hypoechogenicity. US can evaluate the residual motility of the pathological loops, the grade of luminal stenosis and dilatation of proximal segments, and the presence of fistulae, abscesses, and lymphadenopathies. The specificity of US in the identification of the Crohn’s disease is 88–94% while its sensitivity is 73–95% [7]. In the detection of complications, sensitivity and specificity are, respectively, 50–87% and 90–94% for fistulae, 84–100% and 91–97% for stenosis, and 83–100% and 92–94% for abscesses [7]. The morphologic and Doppler appearance of local hypervascularization, resulting from the increased flow in the superior mesenteric artery, correlates well with the severity of the endoscopic and histologic alterations and with inflammatory activity scores [8]. The characteristic of malignant neoplasms of the small bowel are similar to those of the stomach and colon: asymmetrical mural thickening, loss of normal stratification, stenosis, and luminal deformation (Fig. 10.3).

10.6

Computed Tomography Studies of Small-Bowel Disease

The primary requirements of CT imaging of the small bowel are visualization of the entire small bowel, adequate visceral distension, elimination of respiratory motion and peristalsis, and i.v. administration of iodinated contrast agent to evaluate the extent and pattern of wall enhancement. Different types of contrast agents and different modes of administration are used to obtain distension of the small bowel [9]. Hyperdense contrast media

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Radiological Diagnosis of Small-Bowel Diseases

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Fig. 10.2 Small-bowel follow-through examination. a A small-bowel loop is separated from adjacent loops (encircled). b CT confirms a small-bowel mass (arrows). Surgical report: stromal tumor

Fig. 10.3 Ultrasound shows asymmetrical mural thickening, with deformation of one small-bowel loop and the loss of normal stratification and stenosis. Surgical report: adenocarcinoma

(1–2% barium sulfate suspension or a 2–3% watersoluble iodinated solution) are the best known and most well studied. They allow intestinal loop delimitation and the determination of whether an intestinal formation is intraluminal or extraluminal. However, their high density precludes accurate evaluation of the characteristics of the wall of the small intestine. Instead, hypodense contrast agents (oral water, oral oil emulsions, air, low-density barium suspensions, polyethyleneglycol (PEG) solution) ensure better definition of the internal aspect of the small bowel, especially the degree of parietal contrast enhancement after intravenous contrast bolus infusion (Fig. 10.4) [10].

Fig. 10.4 Enterography CT performed after oral administration of hypodense contrast material (PEG) shows mural thickening of the last ileal loop, with target sign (arrow). Good visualization of the normal wall of the ileal loops (I) reveals a linear and homogeneous hyperdense appearance between the endoluminal low-density solution and the extraparietal hypodensity of the peritoneal fat

We recommend PEG for oral use [11, 12] and usually administer 1.5–2.0 L of PEG in doses of 100 ml starting 45 min before the CT examination. Oral contrast agents have the disadvantage of an inadequate, non-uniform distension of all small-bowel loops, particularly the jejunal loops. The problem is overcome, albeit at the expense of higher invasiveness, time, and cost, with CT-enteroclysis. In this method, developed in the early 1990s, variable amounts (2,000–2,750 ml) of low-density (methylcellulose or water) or high-density (4–5% sodium diatrizoate, 1% barium sulfate) are administered via a naso-jejunal tube [9, 10, 13].

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Table 10.1 CT findings in Crohn’s disease CT finding

Definition

Diameter of the smallbowel lumen

Diameter of the loop excluding the thickness of the wall

Diameter of the loop

Diameter of the loop including the thickness of the wall

Stenosis

Decreased diameter of the lumen

Mural enhancement

Hyperdensity of the involved segments

Target sign

Alternating rings of high and low density

Comb sign

Hypervascularity of the involved mesentery manifesting as mesenteric arterial dilation, tortuosity, prominence, wide spacing, and dilation of the vasa recta

Perienteric stranding

Loss of the normally sharp interface between the bowel wall and mesentery

Fibrofatty proliferation

Increased attenuation of the mesenteric fat (-20–60 H.U.)

Fistulas

Communication between two epithelial lined organs (internal fistula) or communication with the skin surface (external fistula)

Lymphadenopathy

Diameter [1 cm

Abscesses

Rounded or oval fluid-density masses delimited by hyperdense wall

On CT, the finding of parietal thickening is the main criterion for the diagnosis of small-bowel disease. Malignant tumors of the small bowel, including adenocarcinomas, carcinoid tumors, lymphoma, stromal tumors (Fig. 10.2b), and metastases, cause asymmetrical mural thickening, loss of normal stratification, stenosis, and luminal deformation. The CT criteria for the diagnosis of small-bowel Crohn’s disease are the essential finding of parietal thickening ([3 mm) and at least one extraparietal inflammatory involvement. CT findings in these patients are listed in Table 10.1, with two examples depicted in Figs. 10.4 and 10.5. Fig. 10.5 PEG-CT (with maximum-intensity projection MIP reconstruction) shows symmetrical thickening of some smallbowel loops (black arrows) and the comb sign (white arrows)

10.6.1 CT and Clinical Disease Activity The CT findings correlate with the clinical activity of the disease. In a previous study [14], we found a significant correlation between mural thickening and the levels of C reactive protein (CRP) and fibrinogen. The target sign and fibrofatty proliferation were present more frequently in patients with a Crohn’s disease activity index (CDAI) score [150 than in those with a CDAI score \150. There was also a statistically significant correlation between the comb sign and abnormal values of CRP, while perienteric stranding correlates with abnormal CRP and fibrinogen levels. Similarly, we found a positive correlation

between the CT relief of fistulas and abnormal ESR and fibrinogen values [14].

10.6.2 CT Versus Ileocolonoscopy in Evaluating Recurrent Crohn’s Disease The evaluation of patients with Crohn’s disease after intestinal resection is another application of CT. In fact, even if medical therapy is the main method of treating patients with Crohn’s disease, approximately

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Radiological Diagnosis of Small-Bowel Diseases

70% of them will undergo surgical intestinal resection at least once in their lives, although disease recurrence is common. Ileocolonoscopy is still the gold standard among the methods for evaluating disease recurrence in patients who have undergone ileal-colic resection. The endoscopic Rutgeerts’ score is an established clinical score for the staging of Crohn’s disease and provides guidelines for further therapeutic strategies. Nevertheless, endoscopy is an invasive method that frequently requires sedation or anesthetization of the patient. Moreover, it can be incomplete in the presence of stenosis not surmountable by the endoscope, and vision is often restricted to the ilealcolic anastomosis, with or without the neo-terminal ileum. In a recent study [15], the sensitivity, specificity, and diagnostic accuracy of CT in the evaluation of the ileal-colic anastomosis were 97, 100, and 97%, respectively. A comparison between CT signs and endoscopic scores in that study shows positive correlations between a score of 4 and the following CT signs: target sign, peri-enteric stranding, comb sign, and fibrofatty proliferation. Moreover, a score of 1 positively correlates with mucosal hyperdensity without wall thickening, and a score of 2 with mucosal hyperdensity with wall thickening.

10.7

MRI Evaluation of Small-Bowel Disease

In patients undergoing MRI for the investigation of small-bowel disease, bowel distension can be achieved with different oral contrast media (water, methylcellulose, PEG, mannitol, superparamagnetic iron particles-SPIO). In enteroclysis-MRI, bowel distension requires duodenal intubation, large volumes of contrast agent (1,500–2,000 ml), and a constant injection rate (80–150 ml/min). Pulse sequences are basically T1- and T2-weighted, although the latter are reserved for assessments of the mucosa and valvulae conniventes, with images similar to those obtained with X-ray. T1-weighted sequences are used in the assessment of the wall and extraluminal space [16]. In Crohn’s disease, the findings are similar to those seen on X-ray. Linear ulcers are recognized on T2-weighted images as hyperintense, fine lesions within the walls. Mural thickening is readily documented both on T2-weighted and post-contrast T1-weighted images [16].

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Fig. 10.6 T2-weighted axial scan with fat saturation shows mural thickening of the last ileal loop with hyperintensity of the wall (short arrow). A collection (long arrow) and fibrofatty proliferation (arrowhead) are also evident

Submucosal edema is visualized as mural thickening with high signal intensity depending on the amount of water (Fig. 10.6) [16]. The cobblestone pattern of Crohn’s disease can be appreciated especially on T2weighted sequences. With optional bowel distension, stenosis and loop dilatation are more accurately assessed than is the case following CT with the oral administration of contrast medium. Fibrofatty mesenteric proliferation appears as irregular, linear, and nodular thickening of adipose tissue, best depicted on T2-weighted images (Fig. 10.6). Fistulae are seen as linear images in the mesentery; they are hyperintense to their water contents on T2-weighted sequences. Abscesses are also hyperintense on T2-weighted images and show wall enhancement on post-contrast T1-weighted sequences [16]. Similar to luminal stenosis, intestinal masses are readily detectable on MRI. They are typically hypoisointense compared to the normal wall. On T2-weighted and pre-contrast T1-weighted images, various patterns of contrast enhancement are seen after Gd administration [17]. Adenocarcinomas, carcinoid tumors, and smooth muscle tumors are usually hypervascularized, showing high-grade contrast enhancement.

10.8

Conclusions

The availability of different procedures requires an in-depth knowledge of their diagnostic possibilities, to be able to select the one best able to specifically reveal a lesion whose presence is suspected based on

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clinical and laboratory findings. Correct imaging of the small bowel should enable the diagnosis of small and early structural alterations as well as the reliable documentation of the normal intestinal morphology.

References 1. Lappas JC, Reyes BL, Maglinte DDT (2001) Abdominal radiography findings in small bowel obstruction: relevance to triage for additional diagnostic imaging. Am J Roentgenol 176:167–174 2. Maglinte DDT, Burney BT, Miller RE (1982) Lesions missed on small bowel follow-through: analysis and recommendation. Radiology 144:737–739 3. Minordi LM, Vecchioli A, Dinardo G et al (2006) The value of the per oral pneumocolon in the study of the distal ileal loops. Clin Radiol 61:1016–1022 4. Herlinger H, Maglinte DDT, Yao Tsuneyosi (1998) Enteroclysis technique and variations. In: Helinger H, Maglinte DDT, Birnbaum BA (eds) Clinical imaging of the small intestine. Springer, New York, pp 95–123 5. Berstein CN, Boult IF, Greenberg HM et al (1997) A prospective randomized comparison between small bowel enteroclysis and small bowel follow-through in Crohn’s disease. Gastroenterology 113:390–398 6. Gourtsoyiannis NC, Papaionnou, Bays et al (1993) Benign tumours of the small intestine: preoperative evaluation with a barium infusion technique. Eur J Radiol 16:115–125 7. Maconi G, Bollani S, Bianchi Porro G (1996) Ultrasonography detection of intestinal complications in Crohn’s disease. Dig Dis Sci 41:1643–1648

L. M. Minordi et al. 8. Giovagnorio F, Diacinti D, Vernia P (1998) Doppler sonography of the superior mesenteric artery in Crohn’s disease. Am J Roentgenol 170:123–126 9. Bender GN, Timmons JH, Williard WC et al (1996) Computed tomographic enteroclysis: one methodology. Invest Radiol 31:43–49 10. Maglinte DD, Sandrasegaran K, Lappas JC et al (2007) CT Enteroclysis. Radiology 245:661–671 11. Minordi LM, Vecchioli A, Mirk P et al (2007) Multidetector CT in small-bowel neoplasms. Radiol Med 112:1013–1025 12. Minordi LM, Vecchioli A, Mirk P et al (2010) CT enteroclysis with polyethylene glicol solution vs CT enteroclysis in small bowel disease. Br J Radiol 84(998): 112–119 13. Minordi LM, Vecchioli A, Guidi L et al (2006) Multidetector CT enteroclysis versus barium enteroclysis with methylcellulose in patients with suspected small bowel disease. Eur Radiol 16:1527–1536 14. Minordi LM, Vecchioli A, Guidi L et al (2009) CT findings and clinical activity in Crohn’s disease. Clin Imaging 33:123–129 15. Minordi LM, Vecchioli A, Poloni G et al (2009) Enteroclysis CT and PEG-CT in patients with previous small bowel surgical resection for Crohn’s disease: CT findings and correlation with endoscopy. Eur Radiol 19:2432–2440 16. Gourtsoyiannis NC, Papanikolau N, Rieber A et al (2002) Evaluation of the small intestine by magnetic resonance imaging. In: Gourtsoyiannis NC (ed) Radiological imaging of the small intestine. Springer, New York, pp 157–170 17. Semelka RC, John G, Kelekis N et al (1996) Small bowel neoplastic disease: demonstration by MRI. J Magn Reson Imaging 6:855–860

Capsule Endoscopy: The Answer to a Challenge

11

Emanuele Rondonotti and Roberto de Franchis

11.1

Introduction

A look at the number of papers focused on the study of the small bowel that have been published in the last 20 years readily reveals a continuous increase. Nevertheless, beginning in 2000–2001, a clear change in the trend of these publications is apparent (Fig. 11.1). This change is not related to an increased prevalence of small-bowel diseases but mainly to the introduction into clinical practice of new diagnostic devices for the study of the small bowel. Before 2001, the main diagnostic tools used to evaluate the small bowel were the small-bowel follow-through (SBFT) study and small-bowel enteroclysis. These two techniques, although specifically designed to evaluate the small bowel, have low sensitivity and specificity in recognizing small and flat lesions. Additionally, both are often poorly tolerated by patients and the results are sometimes difficult to interpret. Indeed, prior to 2001, push enteroscopy was the only way to endoscopically evaluate the small bowel; but, as is well-known, this technique is limited by the depth of insertion of the instrument to the proximal jejunum (about 90–150 cm by the oral route) and to the terminal ileum (50–80 cm by the anal route) and, despite sedation, is poorly tolerated. On the other hand, intra-operative enteroscopy is the most complete but it is also the most invasive means of examining the small bowel [1].

E. Rondonotti (&) Gastroenterology Unit, Ospedale Valduce, Como, Italy e-mail: [email protected]

After 2001, several new endoscopic and nonendoscopic techniques became widely available. The former includes capsule endoscopy and device-assisted enteroscopy, and the latter CT- and MRI-enteroclysis. Among these new devices, capsule endoscopy, mainly due to its technical characteristics, is revolutionary and has resulted in a tremendous shift from insensitive and invasive techniques to a sensitive and patient-friendly examination. Thus, capsule endoscopy is now considered the cornerstone for the evaluation of the small bowel in several clinical conditions. In this chapter, we summarize, based on current evidence and recently released guidelines, the results of capsule endoscopy applications in clinical practice. We also highlight the risks and limitations of this device, an awareness of which has emerged in the 10 years of its use in this setting.

11.2

Indications and Results

The most important feature of capsule endoscopy is the possibility to acquire and transmit more than 50–80,000 images of the small-bowel mucosa without any cable connection. In addition, the capsule is easily swallowed with a single sip of water by people of almost any age (older than 8 years). Once the capsule is swallowed, the examination can begin without the need for further intervention. And, last but not least, the quality of the images acquired is high and, with the help of specific software, they can be easily evaluated by a dedicated physician. For all these reasons, capsule endoscopy, at least theoretically, is ideal in the diagnosis of any disease affecting the small bowel. However, 10 years after

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Fig. 11.1 Trend of original papers published over time concerning the diagnosis of small-bowel diseases. Search engine: www.pubmed.org. Red line publications addressing the diagnosis of small-bowel tumors (keywords for research: ‘‘small bowel tumors’’). Blue line publications addressing the diagnosis of obscure gastrointestinal bleeding and small bowel

(keywords for search: ‘‘obscure gastrointestinal bleeding’’ AND ‘‘small bowel’’). Green line publications addressing the diagnosis of Crohn’s disease involving the small bowel (keywords for search: Crohn’s disease AND small bowel). Black line overall. The x axis shows the number of papers published; the y axis is the timeline (October 1990–2009)

Fig. 11.2 Indications for capsule endoscopy in clinical practice. The data were derived from a systematic review, published by Liao et al. [3], of more than 2,000 capsule

endoscopy procedures performed worldwide in the last 7 years. OGIB Obscure gastrointestinal bleeding

the introduction of capsule endoscopy into clinical practice, it has become apparent that its use is limited to a few clinical conditions (Fig. 11.2), with the most common indications being obscure gastrointestinal bleeding (OGIB), known or suspected Crohn’s disease, small bowel tumors, and celiac disease [2–4].

11.2.1 Obscure Gastrointestinal Bleeding So far, OGIB is the main clinical indication for capsule endoscopy, and 70–80% of patients undergoing the procedure suffer from this condition. The majority of studies initially published on this application reported a high, although widely variable, diagnostic yield, with a

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Capsule Endoscopy: The Answer to a Challenge

range of 40–90%, and typically 75–80% [5]. These studies, mainly performed in tertiary referral centers, included highly selected patients with a long-standing history of OGIB and low levels of hemoglobin at the time of the examination who had undergone an enormous number of prior examinations, with negative results. Subsequent series comprising larger populations similar to those undergoing capsule endoscopy in everyday clinical practice reported a slightly lower diagnostic yield (50–60%) [3, 4]. Nonetheless, several of those studies (both head to head comparisons and meta-analyses) clearly demonstrated that, in patients with OGIB, capsule endoscopy is superior to traditional radiological techniques (SBFT and small-bowel enteroclysis) and push enteroscopy [6, 7]. At the present time, there have been no comparisons of capsule endoscopy with other recently introduced radiological techniques (CT-enteroclysis, MRI-enteroclysis); however, despite the improved spatial resolution offered by the latter, they remain relatively insensitive in the visualization of small flat lesions. This is particularly the case for angioectasias, which are the most frequent finding identified with capsule endoscopy in patients with OGIB. The factors potentially improving the diagnostic yield of capsule endoscopy include active bleeding at the time of examination, a short interval between the last episode of acute bleeding and capsule endoscopy, low levels of hemoglobin, and a high transfusion requirement [8, 9]. Based on these observations and experience, a ‘‘Standard of practice’’ paper was recently published on behalf of the American Society of Gastrointestinal Endoscopy (ASGE) [10], In this paper, the ASGE Standard of Practice Committee Members reviewed the available evidence and suggested the best diagnostic approach to OGIB. The authors clearly underlined that a careful examination of both the upper and lower gastrointestinal tract, mainly in case of overt GI bleeding, is still mandatory (even repeating an upper GI endoscopy) before addressing the small bowel. However, if the bleeding is correctly defined as obscure (overt or occult) and is suspected of originating from a small-bowel mucosal lesion, then the best way to evaluate the small bowel is capsule endoscopy. For those patients in whom capsule endoscopy is able to show small-bowel findings that clearly explain the reason for referral, a further specific diagnostic and therapeutic workup, such as by means of device-

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assisted enteroscopes, is warranted. In those patients in whom capsule endoscopy is negative, conservative management is often sufficient [11], e.g., by means of iron supplementation in the presence of established deficiency. Alternatively, further investigations may be deemed necessary, in which case the authors suggested repeat capsule endoscopy, especially when the clinical presentation changes; for example, when occult bleeding becomes overt bleeding or when there is a significant drop in hemoglobin levels (at least 4 g/dL). Despite the large experience with capsule endoscopy in clinical practice, studies evaluating the impact of this examination on long-term outcomes are lacking. Indirect evidence shows a positive impact of capsule endoscopy in terms of decreasing the number of further examinations, the need for new hospitalizations, and transfusion requirements, but larger studies are warranted.

11.2.2 Crohn’s Disease The results of a recent consensus meeting, in which experts from the European Crohn’s and Colitis Organisation (ECCO) and the World Organisation of Digestive Endoscopy (OMED) participated, have been published, addressing the role of capsule endoscopy in patients with Crohn’s disease. Specifically, the authors evaluated the use of capsule endoscopy in the following clinical situations: in patients with suspected Crohn’s disease in whom other diagnostic techniques failed, in patients with established Crohn’s disease, in patients with disease recurrence after surgical intervention, and in those with inflammatory bowel disease unclassified (IBD-U) [12]. In patients with suspected Crohn’s disease, the authors found that the available evidence is weak and the quality of the published studies low. In fact, the majority of studies aimed at evaluating the role of capsule endoscopy in patients with suspected Crohn’s disease: (a) included a heterogeneous group of patients, (b) seldom verified over time the final diagnosis by means of other independent diagnostic techniques (e.g., histology), and (c) often used different criteria to classify the lesions identified. Nevertheless, despite these limitations, capsule endoscopy seems to be superior to other diagnostic tools, including SBFT and CT-enterography, in identifying small mucosal

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lesions. However, the specificity for mucosal lesions is low and Crohn’s disease cannot be diagnosed based only on the appearance of the small bowel at capsule endoscopy. Therefore, in case of suspected smallbowel Crohn’s disease, a cross-sectional imaging examination should precede capsule endoscopy. In patients with established Crohn’s disease the authors found a limited role for capsule endoscopy due to the high risk of complications, particularly capsule retention (see below). In these patients, capsule endoscopy should be reserved for those with unexplained symptoms when other investigations are inconclusive, if this will alter management. Accordingly, radiographic imaging takes precedence over small-bowel capsule endoscopy because it can potentially identify obstructive strictures, extraluminal disease, and the transmural nature and/or the anatomical distribution of the disease. Nevertheless, these statements may need to be revised in the future. In general, there is growing interest in identifying possible predictors of patient outcome in Crohn’s disease, in order to choose the most effective therapeutic strategy, mainly when biologic drugs are concerned (i.e., top-down vs. step-up strategy). The predictors thus far identified are young age at onset, specific disease pattern, and small-bowel involvement. Therefore, in the future, at the time of their diagnosis patients with Crohn’s disease may receive a complete and accurate evaluation of the small bowel. In this case, after small bowel strictures (see below) have been excluded, capsule endoscopy would be the tool of choice. It should be noted that the role of capsule endoscopy also seems to be limited in patients with recurrence of Crohn’s disease after surgical intervention. Indeed, capsule endoscopy is often not feasible because of the development of de novo or anastomotic strictures. Thus, for the assessment of postoperative recurrence of Crohn’s disease, capsule endoscopy should only be considered if ileocolonoscopy is contraindicated or unsuccessful. In patients with IBD-U, capsule endoscopy is better than SBFT or enteroclysis in identifying mucosal lesions consistent with Crohn’s disease; in this subset of patients, there are no data comparing capsule endoscopy and either CT- or MRI-enteroclysis. Therefore, it can only be stated that capsule endoscopy can be helpful in identifying mucosal lesions compatible with Crohn’s

E. Rondonotti and R. de Franchis

disease—although a negative capsule endoscopy does not exclude a future diagnosis of the disease. Recently, capsule endoscopy also has been proposed, in the setting of Crohn’s disease, to evaluate mucosal healing after therapy. At the present time, there are several problems with this application: the specificity of mucosal lesions, problems in locating findings along the small bowel, difficulties in sizing findings, etc.; but this truly exciting and promising field deserves further exploration.

11.2.3 Small-Bowel Tumors When compared with gastric or colonic neoplasms, small-bowel tumors are a rare disease, accounting for 1–3% of all primary gastrointestinal tumors. Since the introduction of capsule endoscopy into clinical practice, a few small studies have been published, reporting a frequency of small-bowel tumors ranging between 6 and 9%. However, according to larger, recently published studies the frequency is between 1.6 and 2.4% among patients undergoing capsule endoscopy for any clinical reason. In addition, all published series on capsule endoscopy in the diagnosis of small-bowel tumors underlined that the main clinical indication for the procedure in these patients was OGIB [13]. Small-bowel tumors are seen at capsule endoscopy, regardless of their histological type (i.e., adenocarcinomas, lymphomas, neuroendocrine tumors, gastrointestinal stromal tumors), either as stenoses, polyps, or masses. Therefore, it is not possible to distinguish between different tumors based on their appearance at capsule endoscopy. Although there are no studies formally evaluating the role of capsule endoscopy in the diagnostic algorithm of small-bowel tumors, in light of the above data it can be argued that when there is high clinical suspicion of a small-bowel tumor, such as in case of weight loss and/or obstruction and/or severe anemia, a cross-sectional imaging study of the small bowel should be preferred. Conversely, in reading a capsule endoscopy, when the leading symptom is OGIB, it should be kept in mind that in about 3% of the patients a small-bowel tumor can be identified only by means of this modality.

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Capsule Endoscopy: The Answer to a Challenge

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11.2.4 Celiac Disease

11.2.5 Miscellanea

A few studies explored the performance of capsule endoscopy versus the histological evaluation of smallbowel biopsies taken during gastroscopy in patients with suspected celiac disease. Although all of these studies showed high agreement between these two techniques (sensitivity of capsule endoscopy 85–90%), traditional gastroscopy with duodenal biopsies remains the method of choice to assess mucosal atrophy in patients with suspected celiac disease [14]. However, capsule endoscopy can be a suitable tool in patients with high clinical suspicion of celiac disease who are unable or unwilling to undergo traditional endoscopy. Currently, the main obstacle to the extensive use of capsule endoscopy in the diagnosis of celiac disease is the high cost of the procedure, but also, as highlighted by several authors, the difficulty in grading mucosal atrophy. Capsule endoscopy has also been used in patients with established celiac disease who have maintained a gluten-free diet but with symptoms of recurrence/ persistence or with poor histological recovery, thus necessitating a small-bowel evaluation. While the results of these studies are controversial, the key point seems to be patient selection. For patients with severe symptoms or the appearance of new symptoms such as anemia, capsule endoscopy can play a role in diagnosing the complications of celiac disease, including ulcerative jejunitis, or in identifying other diseases, e.g., small-bowel angioectasias. Conversely, in celiac disease patients on a gluten-free diet with mild symptoms such as abdominal pain but without any alarm symptoms, the role of capsule endoscopy is limited since it shows only the different extents of mucosal atrophy and does not seem to significantly impact further management strategies. Capsule endoscopy does, however, add significant clinical information affecting further management mostly in patients with refractory celiac disease (which is a very rare condition). In these patients, capsule endoscopy can easily identify enteropathyassociated T-cell lymphomas or ulcerative jejunitis, but it does not allow the acquisition of biopsies to confirm the diagnosis. In these cases, the combination of a diagnostic procedure, such as capsule endoscopy or cross-sectional imaging, with device-assisted enteroscopy or other therapeutic procedures allows a final diagnosis to be reached and any further therapeutic strategy to be planned.

Abdominal pain as a possible indication for capsule endoscopy is still largely debated. Although smallbowel tumors have sometimes been identified in patients undergoing capsule endoscopy for unexplained abdominal pain, in these patients the findings are negative in about 80% of cases [15]. By contrast, when chronic abdominal pain is associated with other signs or symptoms (weight loss[10% of body weight, inflammation shown by laboratory tests, chronic anemia, or suspected mid-gastrointestinal bleeding), relevant, or potentially relevant, findings are diagnosed by capsule endoscopy in about 60% of cases [16]. Capsule endoscopy has also been used with promising results in other rare clinical conditions, such as small-bowel transplantation, graft versus host disease, protein-losing enteropathy, primitive lymphangectasia (mostly in the pediatric population), Whipple disease, and irritable bowel syndrome (with clinical suspicion of celiac disease).

11.3

Open Issues

In the last 10 years, as the use of capsule endoscopy has become routine in clinical practice, the technical and clinical limitations of this technique have become apparent. In fact, at the present time, capsule endoscopy is a passive imaging modality that cannot be driven by the operator. Furthermore, it is unable to take biopsies and has a limited power supply (8–12 h, depending on the equipment). Unfortunately, these technical aspects significantly impact the clinical performance of capsule endoscopy. Findings identified at capsule endoscopy are generally not disease-specific and have to be interpreted in the context of the clinical setting, the reason for the referral, and the medications taken by the patients. In addition, in 10–13% of healthy subjects undergoing capsule endoscopy small nonspecific mucosal lesions (such as mucosal breaks or erosions) are found [17]. Several studies clearly demonstrated that capsule endoscopy can miss small-bowel lesions and, sometimes, even large small-bowel tumors. There are no obvious explanations for this inconvenience but the angle of view (140–156°), the quick passage of the device through some tracts of the small bowel,

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Table 11.1 Frequency of capsule retention as a function of the clinical indications for capsule endoscopy (Modified from [20]) Indication for capsule endoscopy

Retention rate (%)

Healthy controls

0

Obscure GI bleeding

1–2

Suspected Crohn’s disease

1–3

Established Crohn’s disease

5–13

Small-bowel tumors

10–25

Intestinal obstruction

20

especially the proximal small bowel, and the presence of food and debris inside the lumen have been suggested. As far as the cleanliness of the small bowel is concerned, despite more than 10 years of experience with capsule endoscopy there is still no standard protocol for bowel preparation. A recently published meta-analysis suggested the administration of 2 L of PEG-based solutions the day before the procedure [18]. However, the weaknesses of the studies included in the meta-analysis and the results of new recently published studies significantly decrease the strength of this recommendation. Even when capsule endoscopy identifies smallbowel lesions, the inter-observer agreement among readers in describing these findings is quite low, especially for relevant findings such as polyps or masses [19]. These discrepancies often necessitate further diagnostic examinations in order to better clarify the diagnosis, thus increasing the number of procedures performed and the costs. Last, but not least, in about 1–2% of patients undergoing capsule endoscopy for any clinical reason the capsule can be retained at the site of a previously unknown small-bowel stricture. Table 11.1 shows the frequency of capsule retention depending on the clinical indication for the procedure [20]. Unfortunately, it is extremely difficult to prevent this complication, including by the routine use of radiological examinations before capsule endoscopy. Clearly, to avoid this complication, patients at risk must be identified, i.e., those with known Crohn’s disease, and, when possible, they should be tested with a blind dissolvable capsule (Agile Patency Capsule, Given Imaging Ltd., Yoqneam, Israel). Once the Agile Patency Capsule is excreted intact, the small-bowel examination with the ‘‘regular’’ capsule can be safely

performed. Nevertheless, in performing this test it must be noted that the size of this particular dissolvable capsule is compatible with only three of the four capsules currently available on the market.

11.4

Conclusions

The advent of capsule endoscopy was a revolution in the field of endoscopy providing high-quality endoscopic images of the small bowel. In the 10 years in which capsule endoscopy has been used in clinical practice for studies of the small bowel, this device has established its superiority over other diagnostic tools previously used for this purpose. Capsule endoscopy does not require sedation, can be easily performed, and is well tolerated and safe; yet everyday experience has also highlighted its limitations (low specificity for mucosal lesions, potential capsule retention). In view of these advantages and disadvantages, capsule endoscopy can be granted a definitive place for some clinical conditions, especially OGIB and clinically suspected Crohn’s disease. In other applications, the device is either still under evaluation (established Crohn’s disease) or not recommended (in the diagnosis of celiac disease). It is important to keep in mind that, when capsule endoscopy was introduced into clinical practice, it was the first imaging modality able to perform studies of the small bowel.

References 1. Rondonotti E, Villa F, Mulder CJ et al (2007) Small bowel capsule endoscopy in 2007: indications, risks and limitations. World J Gastroenterol 14(13):6140–6149 2. Liao Z, Gao R, Li F et al (2010) Fields of applications, diagnostic yields and findings of OMOM capsule endoscopy in 2400 Chinese patients. World J Gastroenterol 16:2669–2676 3. Liao Z, Gao R, Xu C et al (2010) Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc 7:280–286 4. Rondonotti E, Soncini M, Girelli C et al (2010) Small bowel capsule endoscopy in clinical practice: a multicenter 7 year survey. Eur J Gastroenterol Hepatol 22:1380–1386 5. Scapa E, Jacob H, Lewkowicz S et al (2002) Initial experience of wireless-capsule endoscopy for evaluating occult gastrointestinal bleeding and suspected small bowel pathology. Am J Gastroenterol 97:2776–2779

11

Capsule Endoscopy: The Answer to a Challenge

6. Raju GS, Gerson L, Das A et al (2007) American gastroenterological association (AGA) institute technical review on obscure gastrointestinal bleeding. Gastroenterology 133:1697–1717 7. Marmo R, Rotondano G, Piscopo R et al (2005) Metaanalysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases. Aliment Pharmacol Ther 22:595–604 8. Sidhu R, Sanders DS, Kapur K et al (2009) Factors predicting the diagnostic yield and intervention in obscure gastrointestinal bleeding investigated using capsule endoscopy. J Gastrointestin Liver Dis 18:273–278 9. Carey EJ, Leighton JA, Heigh RI et al (2007) A singlecenter experience of 260 consecutive patients undergoing capsule endoscopy for obscure gastrointestinal bleeding. Am J Gastroenterol 102:89–95 10. ASGE Standards of Practice Committee, Fisher L, Lee Krinsky M et al (2010) The role of endoscopy in the management of obscure GI bleeding. Gastrointest Endosc 72:471–479 11. Lai LH, Wong GL, Chow DK et al (2006) Long-term follow-up of patients with obscure gastrointestinal bleeding after negative capsule endoscopy. Am J Gastroenterol 101:1224–1228 12. Bourreille A, Ignjatovic A, Aabakken L et al (2009) Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMEDECCO consensus. Endoscopy 41:618–637

71 13. Pennazio M, Rondonotti E, de Franchis R (2008) Capsule endoscopy in neoplastic diseases. World J Gastroenterol 14:5245–5253 14. El-Matary W, Huynh H, Vandermeer B (2009) Diagnostic characteristics of given video capsule endoscopy in diagnosis of celiac disease: a meta-analysis. J Laparoendosc Adv Surg Tech A 19:815–820 15. Spada C, Pirozzi GA, Riccioni ME et al (2006) Capsule endoscopy in patients with chronic abdominal pain. Dig Liver Dis 38:696–698 16. May A, Manner H, Schneider M et al (2007) Prospective multicenter trial of capsule endoscopy in patients with chronic abdominal pain, diarrhea and other signs and symptoms (CEDAP-plus study). Endoscopy 39:606–612 17. Goldstein JL, Eisen GM, Lewis B et al (2005) Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 3:133–141 18. Rokkas T, Papaxoinis K, Triantafyllou K et al (2009) Does purgative preparation influence the diagnostic yield of small bowel video capsule endoscopy? A meta-analysis. Am J Gastroenterol 104:219–227 19. Pezzoli A, Cannizzaro R, Pennazio M et al (2011) Interobserver agreement in describing video capsule endoscopy findings: a multicentre prospective study. Dig Liver Dis 43:126–131 20. Pennazio M (2006) Capsule endoscopy: where are we after 6 years of clinical use? Dig Liver Dis 38:867–878

Double-Balloon Enteroscopy Alessandro Mussetto and Tino Casetti

12.1

Enteroscopy: An Overview

The twentyfirst century has marked the onset of a revolution in the approach to small-bowel diseases. In particular, the introduction of capsule endoscopy [1] and double-balloon enteroscopy [2, 3] has enabled the endoscopic examination of the entire small bowel, a task that has always been difficult because of the length of the small bowel and its tortuous anatomy in the abdominal cavity. Along with the increasingly widespread use of capsule endoscopy, the increased interest in this technology, and the recognition of its numerous applications, has been the acknowledgement of its limitations: firstly, capsule endoscopy does not allow for therapeutic procedures. Secondly, the examination can be limited by incompleteness, poor bowel preparation or limited mucosal visualization, rapid transit through particular segments, and the unidirectional field of view. Enteroscopy, orally or trans-rectally, can obtain biopsies and/or allows for simultaneous therapeutic intervention, such as the treatment of bleeding lesions, the removal of foreign bodies (often retained capsules), polypectomy, and stricture dilation. Lesions can be tattooed to target subsequent surgical interventions. In addition, enteroscopy can be applied to the treatment and diagnosis of biliary-tract diseases through the bypassed tract, such as a Roux-en-Y

T. Casetti (&) Department of Gastroenterology, Santa Maria delle Croci Hospital, Ravenna, Italy e-mail: [email protected]

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afferent limb. Minor indications are: persistent iron deficiency anemia and/or bleeding in patients after negative capsule endoscopy; unexplained malabsorption or diarrhea; refractory celiac disease; or radiographic abnormalities of the small bowel. Early enteroscopic procedures, such as rope-way enteroscopy and sonde enteroscopy, have largely been abandoned because of their invasive and timeconsuming nature. Instead, they have been replaced by balloon-assisted enteroscopy (double- or singleballoon or NaviAid BGE method) and spiral enteroscopy. Intraoperative enteroscopy, long considered the gold standard of enteroscopy, is also performed less frequently. However, not all lesions can be treated with endoscopic therapy, and a guide to the surgical approach can be useful. Most of the published literature has examined double-balloon enteroscopy, which was the first of the new procedures to be introduced. It is also the subject of this chapter.

12.2

Double-Balloon Enteroscopy

The first report of double-balloon enteroscopy (DBE) appeared in 2001 [2] followed by the introduction of a dedicated system (Fujinon Inc.) in 2003 [3]. DBE is now available worldwide. The first international workshop on DBE was held in Japan in August 2006, with the first Italian DBE workshop held in Cervia in the same year and planned by our G.I. Unit. The principle of DBE starts from the knowledge that insertion would be easier if the intestinal tract could be straightened. In fact, when the endoscope bends in complex fashion or forms a loop, the force

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Fig. 12.1 Double-balloon Fujinon Inc

A. Mussetto and T. Casetti

endoscopy

(DBE)

system

of

applied to the shaft of the instrument is not transmitted to the tip, which, therefore, cannot be advanced further.

12.2.1 Double-Balloon Endoscopy Systems The DBE system (Fig. 12.1) comprises an endoscope to which an inflatable balloon can be attached at the tip, a flexible overtube with a second balloon, always at the tip, and a balloon controller (automatic pressure control) that controls the inflation/deflation of both balloons. A light source and a monitor are also required. Two types of DBE systems are currently available. The standard system consists of a thin endoscope with an 8.5 mm diameter and a 200 cm working length with a 2.2 mm operating channel (Fujinon EN-450P5), a 145 cm soft overtube with an outer diameter of 12.2 mm, and a specifically designed pump. A therapeutic double-balloon endoscope (Fujinon EN-450T5) is also available. The Fujinon EN-450T5 has a larger outer diameter (9.4 mm), in order to accommodate a larger channel (2.8 mm in diameter), with a dedicated overtube.

12.2.2 Technique The DBE procedure can be peformed using either the oral or the anal approach, with the patient under deep or conscious sedation (deep sedation is recommended,

particularly for the oral approach). From the oral route, the depth of insertion and the diagnostic yield are greater than obtained with push enteroscopy (230 vs. 80 cm) [4]. In the oral approach, a single operator initiates insertion of the endoscope. When the endoscope is passed from the incisura to the antrum, the assistant moves the overtube to the white line marked on the endoscope. The line represents a stopping point beyond which the overtube should not be advanced or the endoscope withdrawn: this prevents the overtube from shearing off the endoscope balloon. Next, the operator inserts the endoscope from the descending limb of the duodenum to the third portion of the duodenum and inflates the balloon at the tip of the endoscope. The second operator then moves the overtube along the endoscope to the region of the white line and inflates the overtube balloon, so that the entire apparatus is secured in the intestine, with both balloons inflated. The endoscope is further inserted after its balloon is deflated, with the balloon again inflated at the deepest point (in many patients, this is over the ligament of Treitz); again, the second operator moves the overtube along the endoscope to the white mark and inflates the overtube balloon. After this second stroke, shortening of the small intestine is performed, withdrawing the scope and overtube together, pleating the bowel ‘‘concertinastyle’’ over the overtube. Subsequent inflation and deflation of the two balloons allows the instrument to be advanced (Fig. 12.2). When the desired insertion distance is achieved, the intestine can be marked with a tattoo if there is suspicion of more distal lesions. Withdrawal is initiated with the endoscope balloon inflated, and the overtube balloon deflated. The overtube is retracted and then the overtube balloon is reinflated. Endoscope retraction is always performed with the overtube secured by its balloon, to prevent uncontrolled loss of depth. For the anal approach, a colonoscopy preparation is required. The endoscope and the overtube are advanced to the cecum using the double-balloon push–pull system described above. Then, with the overtube balloon inflated, the endoscope is advanced across the ileocecal valve and its balloon is inflated within the ileum. The overtube is then advanced along the endoscope and into the ileum and the push–pull procedure continued [5] (Fig. 12.3).

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Double-Balloon Enteroscopy

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Fig. 12.2 DBE technique for oral insertion (Courtesy of Tomonori Yano, Jichi Medical University, Japan)

Fig. 12.3 DBE technique for anal insertion (Courtesy of Tomonori Yano, Jichi Medical University, Japan)

DBE is usually performed under fluoroscopic guidance, if the operator is not familiar with the technique. In a recent article, Manner et al. concluded that, compared with non-fluoroscopically guided procedures, fluoroscopy during DBE via the oral route does not provide a significant gain in insertion depth, advancement time, or diagnostic yield [6].

• Mass lesions: endoscopic diagnosis and histologic confirmation of tumors or masses detected by other imaging modalities. • Pre-surgical tattooing for patients undergoing, e.g., small-bowel resection. • Removal of foreign bodies from the small intestine (e.g., retained endoscopy capsule). • Endoscopic access in patients with postoperative altered anatomy: including endoscopic retrograde cholangiopancreatography after Billroth II or Roux-en-Y operation. • In difficult colonoscopy cases.

12.3

Indications

• DBE following capsule endoscopy or radiological imaging: the most common indication and generally performed for obscure gastrointestinal bleeding (OGIB) in patients in whom further diagnostic tests or treatment are indicated. • Mid-gastrointestinal bleeding: in patients with known mid-gastrointestinal bleeding for endoscopic hemostasis. • Diagnosis and treatment of known or suspected stenoses (e.g., Crohn’s disease).

12.4

Results Obtained in the Major Indications

12.4.1 Obscure Gastrointestinal Bleeding According to large published studies, the diagnostic yield of DBE in OGIB ranges from 50 to 75%. Recently, a study of 108 patients with OGIB

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Fig. 12.4 Angiodyplasia Fig. 12.5 Ileal adenocarcinoma

suggested that early DBE is critical to identify the source of bleeding in these patients; yields were significantly higher when the indication was overt ongoing OGIB (100%) than with overt previous (48.4%) or occult OGIB (42.1%) [7]. The causes of bleeding in series studied in Eastern countries are often ulcers or tumors [8], whereas in European and North/South American studies the most common diagnostic finding is a vascular lesion [9, 10] (Fig. 12.4). In a recent retrospective study from Japan, DBE detected bleeding sources in 155 of 200 patients (78%) with OGIB [11]. Small-intestinal ulcers and erosions were the most frequent finding. The time elapsed between the bleeding episode and the endoscopic evaluation was crucial: the yield was higher in the patients who underwent DBE within one month of an episode of overt bleeding compared with patients who did not (84 vs. 57%). The overall rate of bleeding control was 64%. However, the diagnostic yield was similar in DBE and capsule endoscopy in a recent meta-analysis considering small-bowel disease, including OGIB, with a pooled overall yield of 57 and 60%, respectively [12]. Another study [13] compared concordance between capsule endoscopy and DBE in OGIB and showed agreement between the two techniques, especially for polyps or tumors.

12.4.2 Crohn’s Disease Crohn’s disease can be diagnosed using DBE, as histological corroboration is available. Nonetheless,

there are not enough data to recommend DBE in this setting, unless conventional studies (ileocolonoscopy and radiographic imaging) have been inconclusive and an accurate histological diagnosis would alter disease management. Thus, DBE only has a place in patients with obstructive Crohn’s disease, as it allows dilation to be performed [14].

12.4.3 Celiac Disease and Unexplained Malabsorption One paper specifically described the value of DBE in refractory celiac disease [15]; the authors found major lesions (enteropathy-associated T-cell lymphoma or ulcerative jejunitis) in 33% of the patients. Fry and colleagues [16] used DBE to explain the etiology of malabsorption in 42% of a small population (12 patients).

12.4.4 Tumors Small-bowel tumors were found in 2.4% of a large series recently studied with video capsule endoscopy [17]. In a meta-analysis, the diagnostic yield for small-bowel lesions was comparable using DBE and capsule endoscopy [12]; however, DBE is an effective tool for obtaining biopsies for histological diagnosis, for marking lesions before surgery, and for performing therapeutic interventions such as polyp resection or stenting (Fig. 12.5).

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Double-Balloon Enteroscopy

12.5

Route Selection

The localization of a lesion identified at capsule endoscopy is challenging. If DBE is needed, the decision must be made whether to reach the lesion from an oral or a trans-rectal approach. There are currently few published data to guide clinical decision-making. Gay and colleagues [18] found that capsule endoscopy reliably indicated the need for a trans-rectal DBE approach if the transit time to reach a lesion was C75% of the total transit time. Li et al. [19] suggested instead a ratio based on a percentage of the pylorus to ileocecal valve time. Lesions with a time ratio [0.6 were assumed to be located in the middle or distal ileum and should therefore be readily reached by a trans-rectal route. Clearly, the choice of the endoscopic insertion route remains an important issue and can be difficult even with information provided by video capsule endoscopy and/or radiological imaging.

12.6

Complications

With the increasingly widespread use of DBE, complications ensuing from the procedure have been reported. In a large multicenter study, the incidence of complications was 0.8% for diagnostic DBE and 4.3% for therapeutic DBE; there were no fatal cases. The onset of pancreatitis, albeit of unknown etiology, following DBE was reported in 0.3% of cases [20]. A recent review concluded that the most probable cause of pancreatitis in this setting is mechanical straining of the endoscope with the overtube on the pancreas or in the papillary area [21]. The usual recommendation is to avoid inflating the balloons within the duodenum.

12.7

Future Perspectives

With further technological advances and increasing experience, DBE is expected to be useful not only in the diagnosis and treatment of intestinal diseases but also in clarifying their underlying etiologies. Since DBE also can be used to obtain biopsy tissue, its applications include not only histological but also microbiological and molecular biological investigations. Furthermore,

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DBE will likely contribute to the development of new medical agents for treating small-intestinal disease [22].

References 1. Iddan G, Meron G, Glukhovsky A et al (2000) Wireless capsule endoscopy. Nature 405:417 2. Yamamoto H, Sekine Y, Sato Y et al (2001) Total enteroscopy with a nonsurgical steerable double-balloon method. Gastrointest Endosc 53:216–220 3. Yamamoto H, Yano T, Kita H et al (2003) New system of double-balloon enteroscopy for diagnosis and treatment of small intestinal disorders. Gastroenterology 125:1556 4. May A, Nachbar L, Schneider M, Ell C (2006) Prospective comparison of push enteroscopy and push-and-pull enteroscopy in patients with suspected small-bowel bleeding. Am J Gastroenterol 101(9):2016–2024 5. May A, Nachbar L, Wardak A et al (2003) Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy 35:985–991 6. Manner H, May A, Pohl J et al (2010) Impact of fluoroscopy on oral double-balloon enteroscopy: results of a randomized trial in 156 patients. Endoscopy 42(10):820–826 7. Tanaka S, Mitsui K, Yamada Y et al (2008) Diagnostic yield of double-balloon endoscopy in patients with obscure GI bleeding. Gastrointest Endosc 68(4):683–691 8. Chen LH, Chen WG, Cao HJ et al (2010) Double-balloon enteroscopy for obscure gastrointestinal bleeding:a single center experience in China. World J Gastroenterol 16(13):1655 9. Madisch A, Schmolders J, Brückner S et al (2008) Less favorable clinical outcome after diagnostic and interventional double balloon enteroscopy in patients with suspected small-bowel bleeding? Endoscopy 40(9):731–734 10. May A, Nachbar L, Wardak A et al (2003) Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy 35(12):985–991 11. Shinozaki S, Yamamoto H, Yano T et al (2010) Long-term outcome of patients with obscure gastrointestinal bleeding investigated by double-balloon endoscopy. Clin Gastroenterol Hepatol 8(2):151–158 12. Pasha SF, Leighton JA, Das A et al (2008) Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a metaanalysis. Clin Gastroenterol Hepatol 6(6):671–676 13. Marmo R, Rotondano G, Casetti T et al (2009) Degree of concordance between double-balloon enteroscopy and capsule endoscopy in obscure gastrointestinal bleeding: a multicenter study. Endoscopy 41(7):587–592 14. Bourreille A et al (2009) Role of small-bowel endoscopy in IBD: international OMED–ECCO consensus. Endoscopy 41:618–637 15. Hadithi M, Al-toma A, Oudejans J et al (2007) The value of double-balloon enteroscopy in patients with refractory celiac disease. Am J Gastroenterol 102(5):987–996

78 16. Fry LC, Bellutti M, Neumann H et al (2008) Utility of double-balloon enteroscopy for the evaluation of malabsorption. Dig Dis 26(2):134–139 17. Rondonotti E, Pennazio M et al (2008) Small-bowel neoplasms in patients undergoing video capsule endoscopy: a multicenter European study. Endoscopy 40(6):488–495 18. Gay G, Delvaux M, Fassler I (2006) Outcome of capsule endoscopy in determining indication and route for push and pull enteroscopy. Endoscopy 38:49–58 19. Li X et al (2009) Predictive role of capsule endoscopy on the insertion route of double-balloon enteroscopy. Endoscopy 41:762–766

A. Mussetto and T. Casetti 20. Mensink PB, Haringsma J, Kucharzik T et al (2007) Complications of double balloon enteroscopy: a multicenter survey. Endoscopy 39:613–615 21. Kopacova M, Tacheci I, Rejchrt S et al (2010) Double balloon enteroscopy and acute pancreatitis. World J Gastroenterol 16(19):2331–2340 22. Sunada K, Yamamoto H (2009) Double-balloon endoscopy: past, present, and future. J Gastroenterol 44:1–12

Single-Balloon Enteroscopy Mauro Manno, Raffaele Manta, and Rita Conigliaro

13.1

Background

The small bowel was long considered a black box for endoscopists because it could not be routinely examined by way of endoscopic techniques. Standard endoscopy using traditional upper endoscopes can reach up to the first, second, or third portions of the duodenum while push enteroscopy typically reaches distances of about 80 cm past the ligament of Treitz. Colonoscopy may cover a distance of 10–20 cm beyond the ileocecal valve. Thus, most of the small bowel is inaccessible by traditional endoscopic means. In addition, radiographic studies have significant limitations with regard to diagnostic yield, and surgery is an invasive alternative. These limitations have been overcome through the development of balloon enteroscopy, which has since become established throughout the world for diagnostic and therapeutic examinations of the small bowel. Compared with other imaging procedures (e.g., capsule endoscopy and CT scan), the main advantages of balloon enteroscopy are that it allows histologic sampling and endoscopic therapy. With appropriate patient selection, a diagnostic yield for relevant pathologic findings of 70–80% is achieved, while endoscopic therapy can be performed in more than 50% of patients.

M. Manno (&) Gastroenterology and Digestive Endoscopy Unit, Nuovo Ospedale Civile S. Agostino-Estense, Baggiovara di Modena (MO), Italy e-mail: [email protected]

13.2

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The Single-Balloon Enteroscope System

The single-balloon enteroscope (SBE; Olympus, Tokyo, Japan) system was developed in 2006 and introduced into the commercial market in 2007. The rationale behind its development was: (1) to reduce the learning curve for balloon-assisted enteroscopy, (2) to avoid the difficulty encountered in double-balloon enteroscopy (DBE) of attaching the enteroscope balloon to the distal tip of the scope, and (3) to eliminate the requirement of inflating and deflating two balloons in multiple steps, as is the case with the current DBE insertion technique. The SBE system consists of the SIF-Q180 enteroscope, an over tube balloon control unit (OBCU, Olympus balloon control unit), and a disposable silicone splinting tube with balloon (ST-SB1) (Figs. 13.1, 13.2, and 13.3). The enteroscope is a high-resolution video endoscope that works with current Olympus EVIS processors and the EVIS EXERA II system to allow narrowband imaging. It has an outer diameter of 9.2 mm, a working length of 2,000 mm, and a wide operating channel size of 2.8 mm. The field of view is 140°. The splinting tube is an over tube with an inflatable balloon affixed at its distal tip, both in latex-free silicone. Radiopaque material is used in the distal end of the ST-SB1 to allow confirmation of the splinting tube’s tip under fluoroscopy, further enhancing insertion performance into the deep small intestine. The inner diameter of the tube is 11 mm, the outer diameter is 13.2 mm, the working length is 1,320 mm, and the total length is 1,400 mm. The addition of a small amount of water through a small port on the proximal end of the splinting tube activates the hydrophilic

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Fig. 13.1 The Olympus single-balloon enteroscope system (Image courtesy of Olympus Medical Systems Corporation, Japan, with permission)

M. Manno et al.

Fig. 13.3 Single-balloon enteroscope with over tube (Image courtesy of Olympus Medical Systems Corporation, Japan, with permission)

should be turned on before the procedure is started to ensure that the balloon inflates correctly.

13.3

Fig. 13.2 Disposable silicone splinting tube with balloon (ST-SB1) (Image courtesy of Olympus Medical Systems Corporation, Japan, with permission)

coating, thus avoiding friction between the over tube and the enteroscope. Additional water can be flushed into a dedicated port throughout the procedure, in order to reduce friction or wash away debris collected between the enteroscope and the splinting tube. The balloon is inflated and deflated by a balloon control unit with a safety pressure setting range from -6.0 to +5.4 kPa, allowing atraumatic traction on the small bowel mucosa. The OBCU has one button for inflation, one button for deflation, and a third control for the pause/cancel feature. The balloon pump controller

Preparation

No preparation is generally recommended in most cases for SBE performed using an oral approach, except a minimum 12 h fast by the patient. However, in the author’s institution, patients are administered 2 L of a polyethylene glycol (PEG) bowel preparation solution for the anterograde approach and the standard 4 L bowel preparation for retrograde examinations. Limited bowel preparation for oral examinations could improve visibility in the small bowel, where dark bile and debris may compromise deep enteroscopy, as for capsule examinations.

13.4

Sedation

For anterograde SBE, deep monitored sedation (e.g., with propofol) or general anesthesia with intubation is widely accepted. For the retrograde approach, conscious sedation as for colonoscopy is sufficient in most cases. During withdrawal of the endoscope and during therapeutic interventions, the administration of spasmolytics might improve visualization of the small bowel mucosa by reducing motility [1].

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Single-Balloon Enteroscopy

13.5

Insufflation of Gas

As balloon enteroscopies are lengthy procedures, large volumes of air are usually insufflated, leading to significant distension of the small bowel. Indeed, one of the main technical challenges of balloon-assisted enteroscopy is the increasing amount of intraluminal gas, which leads to failure of the procedure. Carbon dioxide (CO2), unlike standard air, is rapidly absorbed from the bowel. Preliminary data indicate that bowel insufflation with CO2 instead of air enhances patient comfort and decreases the need for sedation [2]. Indeed, a randomized, double-blind trial showed that insufflation with CO2 is safe, reduces patient discomfort, and significantly improves intubation depth [3]. However, these results need to be confirmed by other studies before CO2 can be recommended as the standard insufflation gas in balloon enteroscopy.

13.6

Determination of the Primary Insertion Route

The choice of an oral versus anal route for the primary procedure depends on the suspected location of the pathology within the small bowel. In patients in whom balloon-assisted enteroscopy is performed secondary to pathological findings at capsule endoscopy, the latter can obviously indicate the route for balloon-assisted enteroscopy, thus avoiding double procedures. Findings located in the upper two-thirds according to the capsule endoscopy recording indicate balloon-assisted enteroscopy via the oral route, and in the lower third via the anal approach [4].

13.7

Fluoroscopic Control

Fluoroscopy can be beneficial during the initial 10–20 DBE cases, to observe advancement and reduction of the enteroscope and as an aid to determine when looping is present and how to solve it; however, no clinical benefits in the use of fluoroscopy have been demonstrated past the initial learning cases [5]. For some patients with a surgically modified anatomy and

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for those undergoing therapeutic procedures such as dilations, flexible enteroscopy usually requires fluoroscopic guidance.

13.8

Procedure

13.8.1 Balloon-Assisted Enteroscopy by the Anterograde Approach The enteroscope, without over tube, is initially passed into the esophagus with the same technique used for a standard upper endoscopy. After intubation of the pylorus, the enteroscope is pushed into the duodenum until forward advancement is no longer possible. By angulating the tip of the enteroscope in order to hook the intestine, the operator can gently advance the over tube over the enteroscope to the point of maximal insertion, located at 155 cm, where a white line is present on the scope. In order to shorten the intestine and to advance the endoscope into the small bowel, the endoscope and the over tube, with inflated balloon, are withdrawn together. Then, with the balloon still inflated in order to maintain position, the endoscope is pushed maximally into the small bowel. Balloon inflation allows the pushing force applied by the operator to the endoscope to be transmitted to the distal end of the endoscope without further stretching of the intestine. The repetition of these maneuvers guarantees progression of the endoscope and exploration of the small bowel. This is the conventional technique for advancing the endoscope into the small bowel [6] (Fig. 13.4). Modifications of the SBE insertion technique have been proposed. Hartmann and colleagues described an alternative method of SBE insertion (simultaneous technique) that consists of withdrawing only the inflated over tube in order to shorten the intestine, and simultaneously pushing the endoscope as deep as possible into the small bowel. When the splintingtube balloon is near the end of the endoscope, rather than performing the ‘‘pull back maneuver’’ with the splinting tube and angulated scope tip, the angulation is released and the endoscope steered to find the lumen. The over tube, with the balloon still inflated, is

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M. Manno et al.

Fig. 13.4 Representative scheme of single-balloon enteroscopy techniques. (Illustration provided by the author)

pulled back while the endoscope is simultaneously pushed forward. These investigators found that this method works best with two examiners and is more efficient, without sacrificing the depth of insertion or safety [7]. Although arriving at this alternative method independently, the author and his colleagues have performed four procedures using the conventional technique described by Tsujikawa and four procedures using the alternative simultaneous technique, with the aim of prospectively evaluating them. We found that the alternative method allowed a lower mean procedure time (58.3 vs. 65.9 min for the oral approach and 66.4 vs. 74.1 min for the anal approach, using the alternative technique and the conventional technique, respectively). Moreover, the depth of insertion did not differ significantly between the conventional and alternative techniques (240 vs. 250 cm for the oral approach and 180 vs. 160 cm for the anal approach, using the alternative technique and the conventional techniques, respectively). These results did not correlate with the skill of the operators,

who were the same two operators already experienced in DBE [8]. Of course, these two techniques can be alternately used in the same exam. During the majority of examinations, forward advancement is at some point no longer possible. The maximal depth of insertion will be reached earlier in patients with adhesions from prior surgeries or due to other inflammatory disorders. At the point of maximal insertion, the area should be marked with a tattoo of India ink, injected with a sclerotherapy needle; alternatively, a clip can be positioned. This marker can then be visualized during subsequent capsule endoscopy examination or balloon-assisted enteroscopy performed during the opposite approach. Total enteroscopy is achieved when a balloon- assisted enteroscopy examination performed from the opposite approach visualizes the marker placed during the initial examination. To estimate the depth of insertion, the method proposed by May et al. can be used, recording data on a standardized documentation sheet. This method

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Single-Balloon Enteroscopy

was validated in an animal model during training courses and shown to be accurate, with a mean deviation of less than 10%. For each advancement of the enteroscope, the distance traversed, usually between 20 and 40 cm, is recorded. Any portion of an advancement that is lost during a reduction manoeuvre is then subtracted from this value. Alternatively, counting folds in 10 cm increments can estimate the depth of insertion during withdrawal [9]. Once the point of maximal insertion is reached and a marker is placed, the enteroscope can be gradually withdrawn with use of the SBE system. The over tube is gently withdrawn backward toward the proximal end of the enteroscope without moving the enteroscope until the over tube is at the shaft of the enteroscope. Next, the over tube balloon is inflated and the enteroscope slowly withdrawn until it reaches the distal end of the over tube. With this technique, the enteroscope can be withdrawn in a controlled fashion. It is recommended that any condition visualized during advancement be treated, particularly angiodysplasia because it could be difficult to distinguish arteriovenous malformations from the mild mucosal trauma incurred by the enteroscope during the withdrawal process.

13.8.2 Balloon-Assisted Enteroscopy by the Retrograde Approach The retrograde SBE route is challenging, even for expert endoscopists. While the learning curve for anterograde procedures is estimated to be approximately 10 cases [5], for the retrograde approach it is typically 20–30 cases. Even when performed by experienced endoscopists, ileal intubation has failure rates of 20–30%, especially in the presence of adhesions from prior pelvic surgeries and appendectomy and due to the flexible nature of the enteroscope, which creates advancement through the colon and subsequent difficult intubation of the ileum [10]. Accordingly, it is recommended to start using the SBE system, performing reduction manoeuvres when looping is first appreciated in the colon. Initial attempts at ileocecal valve intubation should be conducted with the patient in the left lateral or supine position in order to achieve an ideal location of the valve between the 3 and 9 o’clock positions. In

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case of failure, the patient’s position should be changed (prone or right lateral decubitus position) [11]. If these manoeuvres are unsuccessful, use of a ‘‘tripleballoon technique’’ with an inflated balloon dilator inserted through the channel of the SBE has been demonstrated to be useful in some cases [12].

13.9

Complications

The complications of SBE may be the result of the procedure itself or they may be secondary to anesthesia. Relevant complications in diagnostic balloon-assisted enteroscopy can be expected in approximately 1% of cases. As in conventional endoscopy, the risk is higher (3–4%) in therapeutic enteroscopy [13]. Among the 484 SBE procedures published to date, only one perforation (0.21%) occurred during diagnostic SBE (in a patient with postoperative ulcerative colitis), and only one perforation (0.41% of the total SBE) occurred during therapeutic enteroscopy (balloon dilation) [6, 14–18]. However, scrupulous care is required when moving the endoscope past a smallintestinal lesion or when treating patients with known adhesions or strictures. In contrast to per oral DBE, acute pancreatitis has not been reported following SBE. In DBE, the hypothesized mechanisms of acute pancreatitis onset are: (1) the inflation of the two balloons in the duodenum, resulting in an increase of intraluminal pressure, leading to the reflux of duodenal fluids into the pancreatic duct and (2) the repeated ‘‘push-and-pull,’’ with stretching of the small intestine [19, 20]. In our opinion, the lower incidence of acute pancreatitis after SBE is mainly due to the differences in the two techniques. In the proposed SBE technique, after the enteroscope is passed into the third duodenal portion, the over tube is advanced and the balloon is inflated away from the papilla. Inflating the balloon too close to the papilla may obstruct the pancreatic duct, either directly or due to post-traumatic edema, resulting in the onset of pancreatitis [18].

13.10 Clinical Cases Specific cases of small bowel disease are presented in Figs. 13.5, 13.6, 13.7, 13.8, 13.9, and 13.10.

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Fig. 13.5 Bleeding jejunal arteriovenous malformation

Fig. 13.8 Intestinal lymphoma

Fig. 13.6 Ischemic enteritis

Fig. 13.9 Intestinal metastasis of a kidney adenocarcinoma

Fig. 13.10 Intestinal metastasis of a bladder sarcoma Fig. 13.7 Jejunal adenocarcinoma

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13.11 Summary Single-balloon enteroscopy is a viable alternative to DBE in the management of small bowel disease. Technically, it is easier to perform, may be more efficient, and, according to the literature data, provides similar diagnostic and therapeutic yields as achieved with DBE.

References 1. Pohl J, Delvaux M, Ell C et al (2008) European Society of Gastrointestinal Endoscopy (ESGE) Guidelines: flexible enteroscopy for diagnosis and treatment of small-bowel diseases. Endoscopy 40:609–618 2. Hirai F, Matsui T, Yao K et al (2007) Efficacy of carbon dioxide insufflation in endoscopic balloon dilation therapy using double balloon endoscopy. Gastrointest Endosc 66:26–29 3. Domagk D, Bretthauer M, Lenz P et al (2007) Carbon dioxide insufflation improves intubation depth in doubleballoon enteroscopy: a randomized, controlled, doubleblind trial. Endoscopy 39:1064–1067 4. Gay G, Delvaux M, Fassler I (2006) Outcome of capsule endoscopy in determining indication and route for push and pull enteroscopy. Endoscopy 38:49–58 5. Mehdizadeh S, Ross A, Gerson L et al (2006) What is the learning curve associated with double-balloon enteroscopy? Technical details and early experience in 6 U.S. tertiary care centers. Gastrointest Endosc 64:740–750 6. Tsujikawa T, Saitoh Y, Andoh A et al (2008) Novel singleballoon enteroscopy for diagnosis and treatment of the small intestine: preliminary experiences. Endoscopy 40:11–15 7. Hartmann D, Eickhoff A, Tamm R et al (2007) Balloonassisted enteroscopy using a single-balloon technique. Endoscopy 39(Suppl 1):E276 8. Manno M, Mussetto A, Conigliaro R (2008) Preliminary results of alternative simultaneous technique for singleballoon enteroscopy. Endoscopy 40:538

85 9. May A, Nachbar L, Schneider M et al (2005) Push-and-pull enteroscopy using the double-balloon technique: method of assessing depth of insertion and training of the enteroscopy technique using the Erlangen Endo-Trainer. Endoscopy 37:66–70 10. Mehdizadeh S, Han NJ, Cheng DW et al (2007) Success rate of retrograde double-balloon enteroscopy. Gastrointest Endosc 65:633–639 11. Gerson LB, Flodin JT, Miyabayashi K (2008) Balloonassisted enteroscopy: technology and troubleshooting. Gastrointest Endosc 68:1158–1167 12. Ross AS, Waxman I, Semrad C et al (2005) Balloon-assisted intubation of the ileocecal valve to facilitate retrograde double-balloon enteroscopy. Gastrointest Endosc 62: 987–988 13. May A (2009) Balloon Enteroscopy: single and doubleballoon enteroscopy. Gastrointest Endoscopy Clin N Am 19:349–356 14. Aktas H, de Ridder L, Haringsma J et al (2010) Complications of single-balloon enteroscopy: a prospective evaluation of 166 procedures. Endoscopy 42:365–368 15. Kawamura T, Yasuda K, Tanaka K et al (2008) Clinical evaluation of a newly developed single-balloon enteroscope. Gastrointest Endosc 68:1112–1116 16. Ramchandani M, Reddy DN, Gupta R et al (2009) Diagnostic yield and therapeutic impact of single-balloon enteroscopy: series of 106 cases. J Gastroenterol Hepatol 24:1631–1638 17. Mensink PB, Haringsma J, Kucharzik T et al (2007) Complications of double balloon enteroscopy: a multicenter survey. Endoscopy 39:613–615 18. Manno M, Barbera C, Dabizzi E et al (2010) Safety of singleballoon enteroscopy: our experience of 72 procedures. Endoscopy 42:773 19. Groenen MJ, Moreels TG, Orlent H et al (2006) Acute pancreatitis after double-balloon enteroscopy: an old pathogenetic theory revisited as a result of using a new endoscopic tool. Endoscopy 38:82–85 20. Heine GD, Hadithi M, Groenen MJ et al (2006) Doubleballoon enteroscopy: indications, diagnostic yield, and complications in a series of 275 patients with suspected small-bowel disease. Endoscopy 38:42–48

14

Spiral Enteroscopy Mauro Manno, Raffaele Manta, and Rita Conigliaro

14.1

Background

The introduction of capsule endoscopy in 2001, followed by balloon-assisted enteroscopy a few years later, radically changed the way the small bowel is diagnosed and treated. Nonetheless, balloon-assisted enteroscopy, designed to facilitate anterograde smallbowel enteroscopy, remains a technically challenging procedure, often requiring extensive time and resources. Spiral enteroscopy is a new technique for endoscopic evaluation of the small bowel. Akerman first proposed the concept and, together with Cantero, in 2006, performed the first procedure. Indeed, development of the Endo-Ease Discovery SB (SB = small bowel; Spirus Medical, Bridgewater, MA) overtube system has revolutionized enteroscopy procedures, which can now be performed more efficiently. The device consists of a smooth, compliant spiral, located at the distal end of the tube, that rapidly gathers and pleats the small bowel. Rotation of the overtube beyond the ligament of Treitz (LOT), i.e., the fixed portion of small bowel, allows the spiral to pleat the intestine in a rapid and controlled manner. With the Endo-Ease Discovery SB, the enteroscope is independently manoeuvered while the overtube remains in place.

M. Manno (&) Gastroenterology and Digestive Endoscopy Unit, Nuovo Ospedale Civile S.Agostino-Estense, Baggiovara di Modena (MO), Italy e-mail: [email protected]

14.2

Endo-Ease Discovery SB Overtube

The Discovery SB (DSB) has an outer diameter of 14.5 mm, an internal diameter of 9.8 mm, an overall length of 118 cm, a spiral height of 5.5 mm, and a spiral length of 22 cm. It includes a locking device that fixes the DSB overtube to the endoscope but still allows rotation of the overtube at the other end. The proximal end of the DSB has two foam handles to assist rotation. The DSB is designed to be used with 200 cm-long enteroscopes with an outer diameter of 9.1–9.5 mm and an endoscope that is 9.4 mm in diameter or less. Specifically, the DSB can be used with the 9.2 mm 200 cm Olympus SIF-Q180 and the 9.4 mm 200 cm Fujinon EN-450T5 enteroscopes, i.e., single- and double-balloon enteroscopes (Fig. 14.1).

14.3

Endo-Ease Vista Retrograde

The Endo-Ease Vista Retrograde (Spirus Medical) is an innovative overtube system that helps endoscopists perform challenging colonoscopies and enables efficient intubation of the terminal ileum. The Vista is 90 cm long with a raised 5.5 mm spiral at the distal end. The spiral is 20 cm in length; the Vista’s outer diameter is 18 mm and its inner diameter 11.5 mm. The Vista fits endoscopes with an outer diameter measuring 10.5–11.6 mm, which allows its use with a pediatric colonoscope or with the 260 cm enteroscope by Olympus (SIF-140). The proximal end of the Vista has a locking collar such

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Fig. 14.1 Endo-ease discovery SB. (Image courtesy of Spirus Medical, with permission)

Fig. 14.2 Endo-ease vista retrograde. (Image courtesy of Spirus Medical, with permission)

that rotation of the Vista locked to the endoscope is possible. The Vista is rotationally advanced over the endoscope to the cecum. For ileal intubation, the coupled device is unlocked and the endoscope is then pushed through the overtube through the ileocecal valve into the ileum (Fig. 14.2).

14.4

Anterograde Spiral Enteroscopy: Technique

The DSB overtube is a sterile single-use device. Two operators are usually required to perform the examination. Before the DSB is installed onto the enteroscope, a small amount of the recommended lubricant should be squeezed into the overtube via the DSB’s proximal coupler. The lubricated DSB is then installed on the enteroscope (Olympus SIF-Q180 or Fujinon EN-450T5). To begin the procedure, the device is locked on the enteroscope at 145 cm, leaving approximately 27 cm of enteroscope past the distal tip of the overtube. This allows the enteroscope to travel through the fixed portions of the upper gastrointestinal tract.

The fixed overtube and enteroscope are advanced slowly, with gentle rotation of the overtube, until the enteroscope typically passes the LOT. It is important to minimize insufflations of air; alternatively carbon dioxide can be used instead of standard air to reducing the formation of a loop in the stomach and to allow better apposition of the spiral with the small bowel. Advancement of the spiral enteroscope begins by passing the spiral past the LOT, whereby the mobile small bowel can be easily pleated on the enteroscope. Early resistance to rotation is almost always due to the formation of a loop in the stomach. In this case, it is helpful to slowly rotate the overtube while gentle withdrawing it; this ‘‘Cantero’’ maneuver may help to advance the scope and to begin engagement of the spiral enteroscope. If this manuever is repeated with abdominal pressure and rotation is still not possible, shortening and straightening the DSB are recommended. The DSB is then unlocked from the enteroscope and the enteroscope is maximally advanced into the small bowel. Next, the overtube is advanced over the enteroscope with gentle slow rotation. This usually installs the spiral past the LOT, allowing the overtube to be straightened and rotated to initiate spiral advancement. Once the maximal depth of insertion has been reached with spiral advancement, it is sometimes possible to pleat additional small bowel by unlocking the enteroscope so that it advances to the maximal insertion depth. With a hook and suction maneuver performed with the enteroscope, the DSB is then rotated and the enteroscope is slowly withdrawn. This can be repeated several times as long as additional depths of small bowel are visualized. When the maximal insertion depth is reached, the withdrawal process begins. The overtube is slowly rotated counter-clockwise, with periodic pauses to allow the small bowel to be carefully visualized. In order to maintain the DSB’s position and to avoid its rapid withdrawal, a slight forward pressure on the DSB should be applied during the counterclockwise withdrawal. Once counter-clockwise rotation is no longer effective, the overtube is returned to 60 cm at the bite block. The enteroscope is then unlocked, slowly drawn back through the proximal jejunum and duodenum, and then fixed to the overtube, with the device withdrawn by applying a slow counterclockwise rotation [1] (Fig. 14.3).

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Fig. 14.3 Representative scheme of the spiral enteroscopy technique. (Scheme courtesy of Spirus Medical, with permission)

14.5

Sedation

For anterograde spiral enteroscopy, the use of propofol and general anesthesia with intubation is strongly recommended. When the overtube spiral is passed through the esophagus during both initial insertion and withdrawal, the endotracheal tube balloon must be deflated in order to minimize any trauma to the tissue between the balloon and the DSB. In the retrograde approach, conscious sedation as for colonoscopy is sufficient in most cases.

14.6

Spiral Enteroscopy Studies

As noted above, Akerman and Cantero were the first to perform a DSB study, using the 200 cm enteroscope such as available from Olympus (SIF Q180) and Fujinon (EN-450T5) [2–4]. Seventy-five patients were prospectively enrolled in the study. The average estimated depth of insertion of the enteroscope past the LOT was *250 cm, with an average total procedure time of 29 min. The diagnostic yield was low (about 26%), which was attributed to the overall young age of the cohort and the lack of a pre-evaluation capsule study.

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Spiral enteroscopy is a rapidly performed technique: deep small-bowel intubation is reached within 20–30 min, reducing the duration of the procedure by almost 50% compared with balloon-assisted enteroscopy. The first reports of anterograde spiral enteroscopy series showed good depths of insertion, with means of 176–247 cm, but with relatively low diagnostic yields (27–36%). Recent clinical trials in tertiary referral centers in Europe and the USA reported similar results in terms of performance parameters [5]. Safety issues were addressed in a large cohort study of 1,750 procedures, published by Akerman et al. in 2009 [6]. Major complications were reported in 0.4% of the patients undergoing spiral enteroscopy procedures. In a recent US study in 61 elderly patients undergoing spiral enteroscopy procedures, mild complications occurred in 7% of the patients and there were no major complications [7]. So far, the complication rate of spiral enteroscopy seems to be comparable with that of double- and single-balloon enteroscopy (DBE and SBE, respectively) systems. Surprisingly, in contrast to the DBE system, there have been no cases of acute pancreatitis after spiral enteroscopy. Thus far, there have been only two head-to-head comparative studies between spiral enteroscopy and balloon-assisted enteroscopy. In the first, a recently published retrospective study comparing anterograde spiral enteroscopy with SBE in 92 patients [8], the mean insertion depth was significantly deeper with spiral enteroscopy than with SBE, 301 and 222 cm, respectively. Other performance parameters were comparable, including total duration of the procedure. The second study prospectively compared anterograde spiral enteroscopy with DBE in 35 patients [9]. The results showed the two techniques to be comparable in terms of performance, including insertion depth, diagnostic yield, and duration. There are as yet only two published Abstracts on retrograde spiral enteroscopy. In the first, a study of 11 patients, retrograde small-bowel enteroscopy was performed using the Vista-SB overtube (outer diameter 18.5 mm) and the Olympus SIF Q-140 260 cm enteroscope. The average total procedure time was 29 min and the estimated maximum depth of insertion 125 cm [10]. In the second study, the Vista SB and a pediatric colonoscope were used in eight patients. The average procedure time was 39 min and the estimated average depth of smallbowel insertion was 113 cm [11].

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14.7

Summary

Spiral enteroscopy is a new technique for deep smallbowel intubation. To date, the performance of spiral enteroscopy has been at least comparable to that of SBE and DBE, thus recommending its use as an interesting alternative technique to balloon-assisted enteroscopy. However, further studies are needed to determine its actual value in patients with suspected small-bowel pathology.

References 1. Akerman PA, Cantero D (2009) Spiral enteroscopy and push enteroscopy. Gastrointest Endosc Clin N Am 19: 357–369 2. Akerman P, Agrawal D, Cantero D et al (2008) Spiral enteroscopy with the new DSB overtube: a novel technique for deep peroral small-bowel intubation. Endoscopy 40:974–978 3. Akerman P, Cantero D, Avila J et al (2008) A pilot study of spiral enteroscopy using a new design 48F Discovery SB overtube and the Olympus 200 cm–9.2 mm enteroscope. Gastrointest Endosc 67:AB264 4. Akerman P, Cantero D, Avila J et al (2008) A pilot study of spiral enteroscopy using a new design 48F Discovery SB overtube and the Fujinon 200 cm–9.4 mm enteroscope. Gastrointest Endosc 67:AB264 5. Mensink PBF (2010) Spiral enteroscopy: from ‘‘new kid on the block’’ to established deep small-bowel enteroscopy tool. Endoscopy 42:955–956 6. Akerman PA, Cantero D (2009) Severe complications of spiral enteroscopy in the first 1750 patients. Gastrointest Endosc 69:AB127 7. Judah JR, Draganov PV, Lam Y et al (2010) Spiral enteroscopy is safe and effective for an elderly United States population of patients with numerous comorbidities. Clin Gastroenterol Hepatol 8:572–576 8. Khashab MA, Lennon AM, Dunbar KB et al (2010) A comparative evaluation of single-balloon enteroscopy and spiral enteroscopy for patients with mid-gut disorders. Gastrointest Endosc 72:766–772 9. Frieling T, Heise J, Sassenrath W et al (2010) Prospective comparison between double-balloon enteroscopy (DBE) and spiral enteroscopy (SE). Endoscopy 42:885–888 10. Akerman P, Cantero D, Pangtay J et al (2009) Retrograde small bowel enteroscopy using the Olympus SIF-140 260 cm enteroscope and the Vista-SB spiral overtube. Gastrointest Endosc 69:AB201 11. Akerman P, Cantero D, Agrawal D et al (2007) Novel method of enteroscopy using Endo-ease Discovery SB overtube. Gastrointest Endosc 65(5):AB125

Surgery for Small-Bowel Disease

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Ugo Grossi, Andrea Mazzari, Pasquina MC Tomaiuolo, Giuseppe Brisinda, and Antonio Crucitti

15.1

Congenital Malformations

Embryological development of the digestive tract is such that it may be entirely or segmentally involved in congenital malformations. These include all the topographic abnormalities: intestinal atresia, gastroschisis and omphalocele, duplications, disorders of intestinal rotation, and small-bowel diverticula, including Meckel’s diverticulum. Patients with any of these conditions are at risk for volvulus, intussusceptions, or bowel obstruction and are thus candidates for early surgical resection [1], with end-to-end anastomosis as the procedure of choice. Laparoscopic procedures are also frequently performed [2–4]. Intestinal atresia describes a partial (stenosis) or complete (atresia) obstruction, the latter with a congenital absence of the bowel lumen. In case of duodenal atresia (prevalence rate of one in 5,000–10,000 births) or jejuno-ileal atresia (prevalence rate of one in 1,000 births), due to the early age of the patient, immediate surgery is required [5]; in fact, bowel distension quickly leads to ischemic necrosis of the bowel. Prenatal diagnosis with fetal echo-tomography can alert the parents as well as the surgeon to the need for postnatal surgery. The end-to-end anastomosis typically involves the resection of 4 cm before the proximal loop and 2 cm from the distal one [6]. Moreover, mucosal neurogangliar lesions are often present in patients with atresia. Only in case of severe peritonitis or prematurity

A. Crucitti (&) General Surgery, Catholic University of Rome, Rome, Italy e-mail: [email protected]

is a temporary ileostomy the preferred approach. In case of non-critical stenosis, surgery can be postponed for months or even years after birth. Gastroschisis and omphalocele are among the congenital anomalies most frequently encountered by pediatric surgeons. Their combined incidence is one in 2,000 births. If the abdomen is closed during the neonatal period, routine pediatric care may suffice; however, if the abdominal-wall defect is one component of a multifaceted anomaly, further care by specialists who are familiar with the child’s particular problems may be required. An infant who is born with gastroschisis may have associated malabsorption, either from in utero injury to the intestine or due to partial bowel obstruction. Anomalies of intestinal fixation accompany the abdominal-wall defects, and midgut volvulus is possible. Atypical appendicitis may occur if the abnormally located appendix is not removed. In addition, these children may have gastroesophageal reflux and their clinical course may be complicated by Hirschsprung disease. Bowel duplications are rare malformations of unknown origin. They generally involve the small bowel, with clinical manifestations mostly evident in the first 2 years of life. The most common site of involvement is the ileum, followed by the esophagus and duodenum [7]. Obstruction, ischemia, and necrosis are the most frequent causes for surgical resection of the affected bowel. Bleeding usually indicates a long communicating duplication, such that the abnormal gastric mucosa causes ulceration of the distal intestinal mucosa. The embryologic development of the midgut can arrest at any phase, with variable consequences: nonrotation, incomplete rotation, and reversed rotation.

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While the early failure of rotation yields the pattern of nonrotation, the latter is a misnomer because the initial 90 of rotation has occurred, with the duodenum lying to the right and the distal colon to the left of the superior mesenteric artery (SMA). Without further rotation, the small bowel is located on the right and the colon on the left. Incomplete rotation represents a failure occurring during the final 180 counterclockwise rotation of the small bowel and/or that of the colon. The resultant abnormality varies from complete non-rotation to a normal anatomy. In reversed rotation, the caudal midgut returns to the abdomen first and the duodenum rotates clockwise rather than the normal counterclockwise. As a result, in reversed rotation the duodenum courses anterior rather than posterior to the SMA and the colon courses posterior rather than anterior to the artery. Rarely, reversed duodenal rotation is accompanied by normal colonic rotation, which may result in an internal hernia. Treatment should be addressed case by case according to the degree of malrotation and the timing of the diagnosis. Exploratory laparotomy may be considered for patients with intestinal obstruction. At surgery, the volvulus should be reduced and any nonviable bowel resected. Treatment of the underlying malrotation includes lysis of all adhesions and abnormal bands, appendectomy, and widening of the small-bowel mesentery [8].

15.2

Diverticula

The following describes two distinct diseases: Meckel’s diverticulum and congenital or acquired diverticulosis.

15.2.1 Meckel’s Diverticulum Meckel’s diverticulum is a true diverticulum originating from the persistence of the onphalomesenteric duct. It was first reported by Fabricus Heldanus in 1650 [9] and thoroughly described by Johann Friedrick Meckel in 1808. This abnormality is mostly asymptomatic and is generally detected incidentally during surgery for other reasons or during a radiological investigation. Patients present with non-specific symptoms. Complications occur in 30–40% and include diverticulitis, peptic ulcer, intestinal intussusceptions, bowel occlusion, hernia, and intestinal

strangulation [10]. Although reported, the presence of tumor is uncommon. The most controversial issue in the management of Meckel’s diverticulum is the decision whether to perform surgical resection in patients who are asymptomatic, i.e., in whom the condition was discovered incidentally. Postoperative morbidity and mortality depend on the indications for removal. While mortality after surgical excision is almost zero, morbidity in asymptomatic patients is 8.6%, which is close to the 8.3% morbidity reported in symptomatic patients (8.5% overall) [11]. Advocates of incidental excision claim that the relatively high mortality and morbidity rates associated with symptomatic disease justify the associated morbidity resulting from elective excision. The opponents of incidental excision quote the low (4.2%) lifetime risk of symptom development. In addition, according to a recent systematic review, there is no compelling evidence to support prophylactic resection [12]. In fact, resection of incidentally detected Meckel’s diverticulum has a significantly higher early morbidity rate than would occur by leaving the diverticulum in situ (5.3 vs. 1.3%) [13]. Nowadays, with the advent of laparoscopy, this scenario has no doubt changed. Laparoscopy permits complete abdominal exploration, increasing the number of incidentally found diverticula. The technique has the advantage that it permits the removal of an incidentally found diverticulum using a gastrointestinal stapling device. Nevertheless, laparoscopy also has been performed to treat patients with Meckel’s diverticulum complicated by intestinal obstruction or bleeding caused by heterotopic gastric mucosa. In adult patients, the following criteria should be evaluated: • Age of the patient: the risk of complications is lower with increasing age • Presence of peritonitis • Condition of the small bowel: healthy, ischemic, or inflamed • Patient condition: ASA score • Elective or emergency surgery • Coincident major surgery or presence of tumor: both are contraindications for removal An additional consideration is the characteristics of the diverticulum: whether it is long and narrow, or there is a possibility of suppuration, whether a mass is palpable or an umbilication present, if there is a risk of intussusception, or the diverticulum is connected to the umbilicus by adhesion bands. All of these are

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conditions for mandatory surgery. A recent perforation could be treated by a resection and immediate bowel reconstruction. A temporary diversion has to be fashioned in case of diffuse peritonitis and if the bowel closure has not been scheduled within the next 3 weeks. Segmentary bowel resection with a terminoterminal anastomosis is the most reliable technique. Ileal resection is an option only if the bowel is perfectly healthy and heterotopic mucosa is not present; generally, a mechanical terminal anastomosis is sufficient. A laparoscopic excision through either a completely intracorporeal approach followed by anastomosis or a mixed approach are other options. It should be highlighted that the procedure does not rule out major surgical resection to avoid the risks associated with the above mentioned complications. Particular attention should be paid to avoid reducing the small-bowel lumen, as this is a frequent cause of postoperative leakage or obstruction.

15.2.2 Diverticulosis Diverticulosis of the small bowel is an infrequent clinical entity; the development of these multiple saclike mucosal herniations are in fact more typical in the left colon. Small-bowel diverticula can be single (30%) or multiple. They are extremely rare in newborns and in children but on rare occasions are seen in adult patients as a consequence of ischemic disease. Duodenal diverticula are approximately five times more common than jejuno-ileal diverticula [14] but the true incidence of either type is unclear because these lesions are usually asymptomatic. The incidence at autopsy of duodenal diverticula is 6–22%. Jejunal diverticula are less common, with a reported incidence of \0.5% on upper gastrointestinal radiographs and of 0.3–1.3% at autopsy. Most cases of duodenal diverticula involve patients older than 50 years, while jejuno-ileal diverticula are commonly observed in patients age 60–70 years. Complications occur in 10–12% of the patients with duodenal diverticulosis and 46% of those with jejunal diverticulosis. They include diverticular pain, bleeding, diverticulitis, intestinal obstruction, perforation and localized abscess, malabsorption, anemia, biliary tract disease, and volvulus [15]. Surgical resection is the treatment of choice and consists of diverticulectomy or segmental resection. In case of multiple sites of

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diverticulosis, medical treatment with antispastics and a low-fiber diet is preferred.

15.3

Small-Bowel Obstruction

Surgical treatment of small-bowel obstruction (SBO) depends on the cause, site, and presence of ischemic lesions or other visceral or parietal lesions. Since the surgical procedures may vary in each case, the different types of SBO are separately discussed below.

15.3.1 Occlusion Occlusion may be adhesion-related, intraluminal, or parietal (Fig. 15.1).

Adhesion-Related Occlusion Intraperitoneal adhesions are the most frequent (90–95%) cause of occlusion after any abdominal surgery [16]; the first episode may occur in a very different setting after weeks, years, or decades after surgery. Rarely a spontaneous adhesion in patients without previous surgery arises as a result of an unrecognized intraabdominal abscess. With the exception of volvulus, the adhesion may cause occlusion in two ways: (1) acute plication such that it involves a small-bowel loop whose antimesenteric margin is stuck either to the abdominal wall at any point, or to a section of mesothelium, or to other abdominal viscera; (2) throttling mechanism of a small-bowel loop through an adhesion stretched between two fixed points of the peritoneal cavity. The adhesion is sectioned with scissors or by electrocoagulation between ligatures wherever it appears to be vascularized. The situation becomes more difficult if the adhesion is very short, with dilatation of several smallbowel loops hindering exposure of the lesion, or if it is located at a difficult site. In such cases, all of the small intestine should be placed outside the peritoneal cavity. The presence of further adhesions or nonocclusive adhesions between small-bowel loops is a common finding and requires a subsequent complete adhesiolysis. Intraluminal Occlusion In contrast to parietal occlusions, intraluminal occlusions are rare, accounting for only 3% of SBO. Most

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Fig. 15.1 Common causes of small-bowel obstruction in industrialized countries

are due to biliary ileus and more rare to foreign bodies. Bilary ileus commonly affects the ileum, rarely the duodenojejunal tract; a gallstone is generally present at palpation and may appear as a discrepancy in the size of the bowel [17]. The stone should be gently separated from the congested bowel and then removed through a cranial (not \10 cm) longitudinal enterotomy of the normal bowel wall. The small intestine is emptied upstream through the enterotomy anterogradely and the entire small bowel should be carefully palpated to identify further calculi in the intestinal lumen, which could cause repeated occlusions. The enterotomy is then closed transversely with interrupted or overlocking sutures. A short small-bowel resection anastomosis, perhaps preceded by retrograde intestinal emptying, may be necessary in case of clear damage to the bowel wall. Bezoars are collections of indigestible matter within the bowel. They are commonly phytobezoars, originating from plant material. Trichobezoars occur secondary to the ingestion of hair and are associated with trichotillomania. The mass may reach the small bowel, a condition described as the Rapunzel syndrome [18].

Parietal Occlusion Several conditions affecting the small-bowel wall may cause occlusion. Primary malignancies of the small intestine, representing about 3% of tumors of the digestive tract, can result in acute occlusion, sometimes related to luminal stenosis but more often to intussusception or volvulus. Cancer of the small intestine (50% of cases) is stenosing; its gross appearance is that of a scirrhous neoplasm, very similar to colon cancer. Sarcoma (30%) rarely causes occlusion and is instead more often associated with torsion and, rarely, stenosis of the lumen. Carcinoid tumors (20%) are typically multiple, whitish, and small and are often seen with synchronous liver metastases. Benign tumors of the small intestine

(adenomas, leiomyomas, fibromas, lipomas) rarely cause SBO except through a mechanism of intussusception. Basically, a wide intestinal resectionanastomosis is required, with digestive resections performed at least 10 cm from the macroscopic limits of the tumor on both sides. A complete exeresis of the affected mesentery is performed, with removal of a triangle whose base is the resected small bowel and whose peak corresponds to the root of the mesentery. A non-traumatic intramural hematoma of the small intestine, without interruption of the intestinal wall, is exceptional. Usually, this lesion occurs in the context of complications related to the use of anticoagulants, e.g., in patients treated with excessive doses of antivitamin K. Abstention typically suffices. Crohn’s disease, intestinal tuberculosis and, rarely, sarcoidosis can cause inflammatory or cicatricial small-bowel stenosis. These generally present as repeated subocclusive crises, but some patients may require an emergency laparotomy if the occlusion is acute. These are frequently patients whose disease goes unrecognized. However, the diagnosis of benign stenosis of the small intestine is easily made and necessitates careful exploration of the entire digestive tract, looking for multifocal lesions. In the absence of complete stenosis, it is better to refrain from performing an emergency resection and instead wait for the results of a postoperative complete evaluation. Only cases of very tight stenosis should be treated with urgent exeresis-anastomosis, ensuring that the limits of resection include the healthy tissue, in order to reduce the risk of postoperative anastomotic fistulization. Successful laparoscopic surgery for bowel obstruction is being reported with increasing frequency, with up to 60% of the cases of SBO caused by adhesions amenable to laparoscopic therapy. The reported conversion rate is 20–51.9% and the complication rate (bowel injury) is 6.5–18.0% [19, 20]. Conversion to an open procedure may be

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secondary to dense adhesions, an inability to resolve the obstruction, intestinal necrosis, intestinal perforation, and conditions not amenable to laparoscopic therapy. Factors that favor laparoscopic success are post-appendectomy SBO, with bands as the cause, patients who have undergone less than two previous surgeries, and shorter duration of symptoms. The conversion rate can be decreased to as low as 6.9% when surgery is guided by preoperative enteroclysis. The laparoscopic treatment of SBO appears to be effective and results in a shorter hospital stay in a highly selected group of patients. The literature also supports that patients treated with a laparoscopic intervention have a lower rate of hernia and postoperative SBO but require the same amount of operative intervention. Patients fulfilling the criteria for consideration of laparoscopic management [21] include those with mild abdominal distention allowing adequate visualization, proximal obstruction, partial obstruction, or an anticipated single-band obstruction. Currently, patients who have advanced, complete, or distal SBO are not candidates for laparoscopic treatment. Unfortunately, this includes the majority of patients with obstruction. Similarly, patients with matted adhesions or those with persistent bowel distention after nasogastric intubation should be managed with conventional laparotomy. Therefore, the role of laparoscopic procedures in the treatment of these patients remains to be defined.

15.3.2 Strangulation The consequences of mechanical SBO include strangulation of both the small bowel and mesentery, leading to ischemia of the bowel wall, which is often severely distended, and the risk of gangrene as well as perforation. Strangulation is the most severe form of occlusion and requires surgical treatment in cases of extreme emergency.

Small-Bowel Volvulus Small-bowel volvulus is due to a twist of a part or the entire small bowel along its mesenteric axis. Primary volvulus is encountered especially in the newborn, sometimes in children, and only rarely in adults, in whom the cause is usually an anomaly that has remained latent. Secondary volvulus is more common and is usually due to an obstacle that subsequently

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immobilizes a small-bowel loop. The obstacle can be in the form of a tumor, a foreign body, an inflammation-related narrowing or scar, Meckel’s diverticulum, a long and ectopic appendix, or an obstructed or strangulated hernia. In cases of straightforward irreversible ischemic injury or perforation, bowel resection becomes essential and must include the entire volvulated loop. The upstream and downstream sections must be macroscopically healthy and extend at least 5 cm from the margins of the lesion. Resection is ideally performed before untwisting the volvulus, to avoid the occurrence of absorption shock, and must still be followed by immediate bowel restoration. If the loop seems to be viable, it should be untwisted and then heated after enteric decompression. Only then can the decision be made to spare or resect the loop, depending on the reversibility of the injury. In the particular case of volvulus of the entire small bowel with a common mesenterium, requiring sub-total resection of the small intestine, the length of the residual small bowel must be carefully measured, as this will determine the nutritional needs of the patient.

Strangled Primitive and Incisional Hernias Internal hernias comprise a group of disparate lesions, often intraoperatively discovered, that commonly show an intraperitoneal orifice that may cause smallbowel strangulation. The orifice may be abnormal (trans-epiploic, trans-mesenteric, or trans-mesocolic hernias), standard (hernias of Winslow’s hiatus), or originate from a developmental abnormality, such as the lack of adherence of the peritoneal leaflets (para-or retro-duodenal, pericolic or intersigmoid hernias). Paraduodenal hernias are retroperitoneal, resulting from the abnormal adherence of the mesocolon and an excessive rotation of the small bowel around the mesenteric axis beyond the traditional 270. Left paraduodenal hernia is the most common. The sac can reach above the spleen and pancreas and down until the pelvis, to the cecum and ascending colon. The hernial orifice is found close to the cecum. Once the content is reduced, the hernial orifice is closed with a few stitches. These should include only the peritoneum to avoid damage to the aorta posteriorly and the inferior mesenteric vessels anteriorly. Pericolic hernia is located in the retrocecal recess, limited anteriorly by the cecum and the ascending colon, posteriorly by the peritoneum of the iliac fossa,

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and laterally by two peritoneal folds: the exterior parieto-cecal fold and the interior mesenteric-cecal fold. In trans-epiploic hernia, a small-bowel loop is strangled through an epiploic orifice of congenital, post-operative, or post-traumatic origin. After reduction of the loop, the epiploic orifice can be simply closed with sutures that avoid blood vessels. Omentectomy is usually unnecessary. Trans-mesocolic hernia of the retroperitoneal space, the most common type, usually contains most of the small bowel incarcerated in the retroperitoneal space of the greater omentum. Since there is no peritoneal sac and the herniated small bowel is stopped secondarily from the rear or by the lesser omentum and gastrocolic ligament it instead penetrates into the peritoneal cavity, either below or above the stomach or, more rarely, through the foramen of Winslow. After reduction of the small intestine, the hernial orifice is closed by a simple suture, with care taken to preserve the mesocolic vessels or, if this is not possible, by inclusion of the margins along the posterior surface of the stomach. Hernia through the foramen of Winslow is the incarceration in the lesser peritoneal sac of a segment of the intestine through this opening. The hernia may affect only the small intestine (ileus or jejunum) or the ascending ileo-colonic tract, sometimes with the right side of the transverse colon. If gentle traction maneuvers through the hiatus do not result in untwisting of the small bowel, a wider opening of the lesser peritoneal sac is required. Once hernial reduction is achieved, the orifice is closed with a strip of peritoneum carefully set at the right edge of the hepatic pedicle and anchorage of the right colonic flexure to the anterior abdominal wall. Diaphragmatic injuries are the most common cause of occlusion as they can result in the strangulation of the small intestine. They may occur as post-traumatic diaphragmatic hernias (90% of cases), in most cases due to an unrecognized rupture of the diaphragm after thoraco-abdominal blunt trauma, and only rarely from a diaphragmatic laceration after open thoracoabdominal trauma. The diaphragmatic gap varies widely in size, a peritoneal sac is almost never involved and other abdominal organs are often strangled together with the small bowel. Alternatively, there may be retro-costo-xiphoid hernia, also known as the Morgagni hernia, which contains the

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transverse colon more often than the small bowel; the oval orifice is usually on the right. A third source of strangulation hernia is the lumbocostal hernia: either a Bochdalek hernia, or, more rarely, hernia of the lumbocostal foramen.

15.3.3 Intussusception Acute intestinal intussusception in adults is rare and is usually secondary to benign or malignant tumors (50–90% of cases), inflammatory lesion (appendix, Meckel’s diverticulum), or foreign bodies within the small intestine [22]. Consequently, the intussusception is mostly ileo-ileal and only rarely jejuno-ileal or ileo-ceco-colic. The lesion is easily highlighted at abdominal exploration, since it is usually found in the right iliac fossa and is seen as a purplish swelling, 5–10 cm long, with the ileal loop upstream fitting within an external cylinder consisting of the downstream ileum or the right colon. Mesenteric lymphadenopathy at this level may be helpful to determine the presence of a neoplastic lesion at the origin of the intussusception. After the lesion is identified, surgical disinvagination is not performed; rather a prompt resection-anastomosis of the small bowel is mandatory.

15.3.4 Obstruction from Other Organic Causes The frequency of radiation-induced SBO increases with the indications for abdominal-pelvic irradiation. These patients often present with severe malnutrition related to subocclusive episodes that preceded the acute ones; accordingly, the surgical risk is greater. Digestive fistulas are frequent and a pre-existing malabsorption may be exacerbated by bowel resection. Considerable advance preparation of the patient for the intervention may be needed, typically 5–15 days, with intensive digestive emptying and parenteral nutrition. The access route depends on the irradiation fields and high incisions are often required. In these cases, viscerolysis is particularly dangerous and difficult, often resulting in multiple injuries of the small bowel; these should be treated with sutures or resections. The absence of tumor recurrence should be

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ruled out. Treatment of radiation-induced SBO results in bowel resection. Peritoneal carcinomatosis often leads to SBO. In most cases an internal by-pass may temporarily solve the occlusion. The lesions may be sufficiently important to prevent any therapeutic action. In this case, the abdominal wall must be quickly closed, without leaving any drains. Otherwise, the obstacle should be located, such as a small-bowel loop incarcerated within a loco-regional tumor recurrence or localized stenosis of the small bowel in a nodule of peritoneal carcinomatosis. The approach in such cases is resection-anastomosis or, in case of unresectable lesions, intestinal bypass.

15.3.5 Functional Obstructions Septic obstructions are a sign of an intraperitoneal infectious outbreak that must be treated specifically. Viscerolysis, enteric retrograde emptying, and peritoneal cleaning with removal of the pseudomembranes must be done cautiously, given the extreme fragility of the inflamed small bowel. As for postoperative occlusions, the suture of an accidental intestinal hole exposes the patient to an increased risk of postoperative fistula; instead a temporary enterostomy is often the preferred measure. Acute idiopathic small-bowel pseudo-obstruction is an extreme situation arising in the course of an urgent laparotomy for acute SBO. In such cases, the surgeon discovers an overall dilated small bowel, with no clear sites of occlusion. The treatment is limited to retrograde intestinal decompression.

15.4

Crohn’s Disease

The diagnosis and treatment of Crohn’s disease can be difficult even for gastroenterologists and surgeons, due to the wide spectrum of intestinal and extraintestinal manifestations. Patients with CD often require surgery as their disease progresses, with the timing of surgery being one of the critical details of the clinical history of these patients. Generally, surgery becomes more likely, the longer the disease duration. The initial management of patients with CD is medical, until treatment fails or a complication arises. Surgery is considered only for CD patients in

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whom medical treatment has failed, or in cases of severe secondary effects, or in the presence of surgical complications such as occlusion, fistulas, or abscesses. Symptoms are precipitated by a single stricture or multiple strictures or a lengthy diseaseinvolved intestinal segment and differ depending on the location of the disease in the gastrointestinal tract. Even a complete obstruction in CD tends to resolve with nasogastric decompression, intravenous hydration, and medical therapy, allowing surgery to be postponed until resolution of the clinical picture allows for a definitive procedure. Intestinal fistulae occur in 33% of CD patients [23] but are the primary indication for surgery in only a minority of patients. Enterovesical fistulae are seen in 2–5% of patients with CD [24] and often result in recurrent urinary tract infections, including pyelonephritis. While it is not mandatory to operate on all patients with enterovesical fistulae, surgery is warranted to avoid the deterioration of renal function. Enterocutaneous fistulae usually drain through a previous abdominal scar or through the umbilicus. In some cases, they are the result of surgical incision and drainage of a subcutaneous abscess complicating severe intra-abdominal disease or from percutaneous drainage of an abdominal abscess. Patients may be reluctant to undergo surgical treatment when the enterocutaneous fistula has a minimal output and the underlying disease is under satisfactory control. Enterovaginal fistulae are rare complications of CD and occur only in women who have undergone a previous hysterectomy. The vaginal discharge is a source of discomfort, social and sexual embarrassment, and difficulty in maintaining personal hygiene. A trial of medical therapy may be elected for enterocutaneous and enterovaginal fistulae, but most cases require surgery and the majority of patients readily accept surgical intervention. Enteroduodenal, enteroenteric, and enterocolic fistulae are usually asymptomatic and often discovered only during a careful abdominal exploration or at examination of the resected specimen [25]. While less frequent than fistulae, intra-abdominal abscesses and inflammatory masses more commonly necessitate surgical intervention. However, despite successful percutaneous drainage, the abscess will very likely recur or cause an enterocutaneous fistula, as a consequence of the disease severity in the intestinal segment from which it originated. Accordingly,

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surgical resection is usually recommended for these patients. Large intraloop abscesses are a rare occurrence and are often successfully treated by open surgical drainage. Inflammatory masses point to the presence of severe disease and commonly contain an unrecognized abscess. Thus, patients with inflammatory masses that do not readily respond to antibiotic treatment should be considered as candidates for surgical treatment. Free perforation is a rare complication of CD, occurring in only about 1% of cases [26], but it is an obvious indication for urgent operation. Hemorrhage is an uncommon complication in patients with CD. It necessitates a thorough diagnostic work up to determine the source of bleeding, which in many cases is not related to CD. For example, patients on chronic steroid therapy may develop peptic ulcer disease. In patients with small bowel disease, hemorrhage is rarely obvious but rather chronic, causing anemia but rarely requiring urgent surgery. Massive gastrointestinal hemorrhage occurs more frequently against a background of colitis. Angiography can localize the site of bleeding in the presence of brisk hemorrhage; otherwise, upper endoscopy and capsule endoscopy can identify the bleeding source in the duodenum and small bowel, whereas colonoscopy can be employed for the large bowel. Intraoperative localization is facilitated by enteroscopy or colonoscopy. The possibility of a life-threatening hemorrhage in a CD patient should not be underestimated since five cases of exsanguinating gastrointestinal hemorrhage have been reported in patients with CD. CD is a preneoplastic condition with an increased risk for adenocarcinoma of the affected intestinal segment. The risk of colorectal cancer in Crohn’s colitis is 4–20 times higher than in the control population [27], with an incidence between 1.4 and 1.8% [28]. The preoperative diagnosis of adenocarcinoma of the small bowel is difficult because the symptoms and radiographic findings of a small-bowel malignancy can be similar to those of the underlying CD. Male patients and patients with long-standing disease appear to be at increased risk for small bowel adenocarcinoma. Defunctionalized bowel segments also seem to be particularly vulnerable to malignancy. For this reason, bypass surgery should be avoided and defunctionalized rectal stumps should either be functionally restored or excised. Once the need for surgical intervention has been established, the surgical strategy will vary depending on the portion of the

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Fig. 15.2 A long stricture in a patient with Crohn’s disease

intestine involved by CD. The Heineke–Mikulicz pyloroplasty can be used in patients with short Crohn’s strictures of the first, second, and third portions of the duodenum; the Finney strictureplasty lends itself better to longer strictures in the first and fourth portions of the duodenum. The jejunum and ileum are involved by CD in 3–10% of patients [29]. The two most common indications for surgical treatment are obstruction and sepsis; massive hemorrhage and carcinoma are much less common. Chronic, high-grade, SBO may be caused by single or multiple short or long strictures (Fig. 15.2). These patients present with postprandial abdominal cramps, nausea, and vomiting and their condition often progresses to a complete obstruction. Due to the need for a second operation in as many as 30% of patients, short-bowel syndrome reportedly occurs in up to 12.6% of cases [30]. Currently, the Heineke– Mikulicz, the Finney, and the side-to-side isoperistaltic approach are three most commonly performed strictureplasty techniques. In general, the Heineke– Mikulicz strictureplasty is used for short strictures (up to 7 cm in length), the Finney strictureplasty for longer strictures (up to 10–12 cm), and side-to-side isoperistaltic strictureplasty for multiple sequential strictures. Strictureplasty is contraindicated in the presence of active sepsis when the bowel wall is thick and unyielding or in patients with severe weight loss and marked hypoalbuminemia. Small-bowel carcinoma in patients with CD is treated with a radical segmental resection when feasible. The prognosis for these patients is poor, with survival rates of 23% at 3 years and 5% at 5 years [31]. Cancers in bypassed

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loops or in defunctionalized stumps can reach advanced stages before they become symptomatic. The terminal ileum is the most common Crohn’s affected site requiring surgery and accounts for approximately 40–50% of the CD patients referred to the surgeon [32]. In the majority of cases, the patients present with symptoms of obstruction or sepsis, both of which point to a contained perforation or an abscess with or without a fistula. For obstructive primary disease involving exclusively the terminal ileum without septic complication, the treatment is resection, either in the form of an ileocolic resection or a formal right hemicolectomy if there is significant involvement of the ascending colon. If CD is complicated by the presence of an abscess the method and timing of intervention require careful decisionmaking. In almost half of these cases, percutaneous drainage not only allows most patients to avoid early surgery but it is also associated with a shorted hospitalization stay [33]. Large intraloop abscesses are not easily approached percutaneously, thus necessitating surgery instead. Retroperitoneal perforation of the ileocecal region may give rise to a psoas abscess, which can create a chronic inflammatory reaction at the pelvic brim featuring ureteral stenosis and right hydronephrosis. The abscess should be drained and the diseased terminal ileum resected; these measures should relieve the compressed ureter and resolve the hydronephrosis.

15.5

Neoplasms

While the small bowel accounts for 80% of the total intestinal length and 90% of its absorptive surface, small-bowel neoplasms (SBN) comprise just 3.1% of all intestinal cancers [34]. In the USA, it is estimated that almost 7,000 cases of SBN will be diagnosed and that in 2011 around 1,100 people will die of cancer of the small intestine [35]. As benign neoplasms are discovered more often in autopsy series, malignant neoplasms make up 75% of the symptomatic lesions that lead to surgery. Several risk factors and associated conditions have been identified as related to SBN. These include familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, Crohn’s disease, and celiac disease.

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15.5.1 Benign Neoplasms The most common benign neoplasms are adenomas, benign gastrointestinal stromal tumors (GISTs), and lipomas. Among these, benign GISTs, including leiomyomas, are the most common symptomatic benign tumors of the small bowel. These tumors may present with intramural or a mixed intramural– extramural pattern of growth. SBO is common in the first pattern. Leiomyomas can reach considerable sizes and they often outgrow their blood supply, resulting in bleeding manifestations. In such cases, surgical resection is necessary. Adenomas account for 15% of benign small bowel tumors. Most (50%) are found in the ileum, with about 30% in the jejunum and 20% in the duodenum. Malignant degeneration occurs in 35–55% of the cases, according to the literature. Adenomas are usually discovered secondary to abdominal pain or bleeding. Segmental resection is the treatment of choice. Lipomas are most common in the ileum and generally present as single, intramural, submucosal lesions. Excision is required in symptomatic lesions (mostly SBO). As lipomas show no malignant potential, they should be removed only if the resection is simple when intraoperatively discovered.

15.5.2 Malignant Neoplasms Of the malignant SBN, neuroendocrine tumors (NETs) comprise 36.5%, adenocarcinomas 30.9%, sarcomas and GISTs 10.0%, lymphomas 18.7%, and miscellaneous and non-specified neoplasia 3.9%. The only curative treatment for gastrointestinal NETs is radical surgical resection. Surgery alone or in combination with other therapeutic options may be used as palliative treatment for patients with unresectable disease, and has been shown to increase median survival, decrease tumor burden, facilitate symptom control, and prevent complications. Surgical excision, lobectomy, or ablative techniques (hepatic artery embolization, cryoablation and radio frequency ablation) reduce tumor load in NETs with hepatic metastases. These procedures are associated with clinical symptomatic improvement and may extend 5-year survival. Liver transplantation has been utilized with success in a minority of patients.

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The only curative treatment for small-bowel adenocarcinomas is complete surgical resection but this is often impossible due to late diagnosis and thus local extension and extensive metastasis. Jejunal and ileal adenocarcinomas should be aggressively treated with en bloc or segmental resection and primary anastomosis. An overall increased survival for patients with smallbowel adenocarcinoma treated with combined chemotherapy and surgery has been noted, however, further randomized controlled trials are required to evaluate the effectiveness of adjuvant chemotherapy. The management of primary non-Hodgkin lymphoma (NHL) is debated, although surgical exploration is initially warranted for correct diagnosis and staging. In a Japanese study of 96 patients with primary intestinal lymphomas, 47% were treated with surgery alone, 16% chemotherapy or radiotherapy, and 35% chemotherapy plus radiotherapy. In the 2% who received no treatment, overall survival was better than that of patients who underwent surgery, but event-free survival did not differ between two groups. T-cell lymphomas disseminate early such that complete surgical resection is usually not feasible. In the treatment of patients with sarcomas and GISTs, the primary aim should be complete surgical resection with negative margins, avoiding the occurrence of tumor spillage. Localized GISTs should be removed en bloc, respecting a possible pseudocapsule and avoiding intraperitoneal dissemination. Adjacent organs adherent to the tumor should also be resected en bloc. Medical treatment with Imatinib is indicated in patients with unresectable, metastatic or recurrent GISTs, adjusting the dose of the drug according to response. Some patients may benefit from repeat surgical excision of focal GIST progression. Leiomyosarcomas are resistant to both radio- and chemo-therapy. Surgical resection involving both the tumor and adjacent mesentery offers the only potential cure.

thrombosis), mesenteric venous thrombosis, and nonocclusive mesenteric ischemia.

15.6.1 Mesenteric Arterial Occlusion Rapid operative disobliteration of the obstruction is the standard treatment in patients with occlusive mesenteric arterial ischemia. Perfusion and viability of the intestine are assessed after a generous midline incision. In embolic mesenteric artery occlusion, the proximal jejunum is usually of normal appearance. All other parts of the small intestine and the colon, up to the transverse colon, may be involved. If SMA embolus is suspected, a transverse arteriotomy in the artery’s main trunk is preferred, after the patient is systemically heparinized. The arteriotomy should be proximal to the middle colic artery. After successful proximal and distal embolectomy, 20–30 min of reperfusion time should be permitted before bowel resection is performed. A scrupulous intraoperative assessment of bowel viability is necessary to minimize bowel resection. Inspection of intestinal color, visible arterial pulsations, and peristaltic activity, with palpation of bowel texture and arterial pulsations are useful parameters. Doppler signals, when present, suggest bowel viability. A ‘‘second look’’ operation may be performed 12–24 h later to re-inspect areas of questionably viable intestine, aiming at reducing the extent of resection at primary exploration. Overtly necrotic bowel, of course, has to be resected, possibly with a stoma. If the small bowel is gangrenous, enterectomy with life-long intravenous alimentation is the only option. In patients with mesenteric artery thrombosis, the proximal jejunum is usually involved in the ischemia. Operative revascularization is performed by thrombectomy, if possible, or (usually) with a bypass.

15.6.2 Mesenteric Venous Thrombosis

15.6

Acute Mesenteric Ischemia

Acute mesenteric ischemia (AMI) is a life-threatening condition with mortality rates still ranging between 60 and 100% [36]. The subsets of AMI include mesenteric arterial occlusion (by embolus or

Anticoagulation therapy should be considered whenever a diagnosis of mesenteric venous thrombosis is made. Conservative treatment is an option in patients without peritonitis and any signs of bowel necrosis. Conversely, all patients with localized or diffuse peritonitis should immediately undergo exploratory laparotomy. Minimal bowel resection is

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the treatment of choice, with second-look laparotomy as a highly recommended option.

15.6.3 Non-occlusive Mesenteric Ischemia The main pathophysiological mechanism in nonocclusive mesenteric ischemia (NOMI) is mesenteric vasoconstriction, which of course cannot be corrected by surgery. Thus, surgical exploration in patients with NOMI is limited to those with peritoneal signs. The treatment of NOMI is basically pharmacological, consisting of selective infusion of papaverine in the SMA. Nevertheless, repeated angiogram and the patient’s clinical symptoms and signs should not delay surgical treatment, which may be avoided only after the radiologically confirmed resolution of vasoconstriction and the absence of peritoneal signs.

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Index

A Abdominopelvic infection, 44 Acute mesenteric ischemia, 100 Anisakis simplex, 44 Ascariasis, 45 Autoimmune enteropathy avium-intracelluare, 47 Anemia, 13 B Back wash ileitis, 16 Balloon-assisted enteroscopy, 25, 73, 79, 81, 87, 89, 90, 283 Bauhin valve, 1 Bowel inflammation, 56

C Capsule endoscopy, 15, 26, 31, 32, 42, 48, 65–70, 73, 75–77, 79, 81, 98 Capsule retention, 49, 68, 70 Cecal region, 13 Cecum, 1 Celiac disease, 16, 31, 51 Children, 47–50 Chromendoscopy, 8 Chronic diarrhea, 13 Chronic non-blood diarrhea, 14 Colonoscopy, 13 Colorectal cancer, 39, 47, 54, 55, 98 Computed tomography, 14 Computed Tomography Studies of Small-Bowel Disease, 60 Confocal laser endoscopy, 16, 25–27 Confocal laser endomicroscopy, 16 Congenital malformations, 91 Crohn’s disease, 13, 42, 43 Cryptosporidium parvum, 44 CT and Clinical Disease Activity, 62 CT Versus Ileocolonoscopy, 62

D Device-assisted enteroscopy, 65, 69 Diarrhea, 13 Direct Abdominal Radiography, 59

Disease, 62, 63 Disease activity, 35, 39, 62 Disease and Malignancies, 60 Diverticulosis, 92, 93 Double contrast barium enema, 2 Double-balloon endoscopy, 73, 74 Duodenoscopy, 31 Drug-induced colitis, 14 E Eariy colorectal cancer, 3 Endoscopy with a magnifying, 32 Endoscopy, 2, 14 Enteroclysis, 59–61, 63 Enteroscopy, 21, 25, 48–50, 79–83, 85, 87–90 Esophagogastroduodenoscopy, 14 Enterography, 14 Evaluating recurrent crohn’s disease, 62 F Fexible sigmoidoscopy, 7 FICE, 5 G Gluten, 31 Granuloma, 53, 54 H HDTV, 22 Histology, 14 Histoplasma capsulatum, 44 HIV-infected patients, 17 I IBD, 13, 14, 18, 35, 39, 47, 67, 68 Ileal disease, 41 Ileitis, 16 Ileocecal valve, 1, 13 Ileocolitis, 55 Ileoscopy, 13, 22, 23, 25, 27, 47, 48, 50

A. Trecca (ed.), Ileoscopy, DOI: 10.1007/978-88-470-2345-1, Ó Springer-Verlag Italia 2012

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I (cont.) Ileum, 1-5, 13-18, 21-23, 32, 35, 37, 41-43, 48, 50, 56, 59, 65 Infectious ileitis, 42 Inflammation, 2, 32, 37-39, 54, 55, 60, 69, 95 Inflammatory bowel disease, 13, 47 Intestinal resection, 62, 63 Intestinal tuberculosis, 16, 41, 42, 45 Intra-operative ileoscopy, 32, 48, 50 i-Scan, 23–25 Ischemia, 91, 95, 100, 101 Intraepithelial lymphocytes, 32 Inderterminate, 14

Index S Sessile serrated adenoma/polyp, 10 Single-Balloon Enteroscopy, 85 Small bowel, 91–100 Small bowel enema, 14 Small intestine, 1 Small-Bowel Follow-Through Study Peroral Pneumocolon, 59 Small-bowel follow-through study, 14 Small-bowel neoplasms, 99 Small-bowel obstruction, 93 Small-bowel tumors, 68-70, 76 Spiral Enteroscopy, 87–90 Surgery, 91–95, 97–100 Surgical resection, 91–93, 98–100

L Laterally spreading tumor, 9 M Magnetic resonance, 35 Magnification, 8, 17, 21–25, 32, 55–57 Magnification Endoscopy, 22, 23 Magnified ileoscopy, 4, 5, 48 Magnifying chromoendoscopy, 22 Malabsorption, 49, 76, 91, 93, 96 Malformation, 91 Microsatellite instability, 2 MRI Evaluation of Small-Bowel, 63 Mycobacterium avium-intracellulare, 43 N Narrow band imaging, 3, 8 NBI, 23–25 Neoplasms, 99 Nonspecific ileitis, 17 Nodular lymphoid hyperplasia, 16 O Obscure bleeding, 47 Obscure gastrointestinal bleeding, 49, 66, 75 Obscure GI bleeding, 70 Occlusion, 92–97, 100 P Pediatrics, 48, 49 PEG, 61, 63, 78 Peroral pneumocolon, 59 Pit pattern, 8 R Retrograde ileoscopy, 41, 42, 44 Right lower quadrant abdominal pain, 13

T T lymphocytes, 53 Terminal ileoscopy, 13 Terminal ileum, 1, 13, 32, 53, 54, 56 Traditional serrated adenoma, 7 Tumors, 7, 8, 49, 51, 53, 57, 60, 62, 63, 66 U Ulcerative colitis, 14 Ultrasonograpy, 59 Ultrasound Appearance of Crohn’s Disease and Malignancies, 60 V Videocapsule endoscopy, 31 Villous adenoma, 2, 32 Villous atrophy, 32 Villous profile, 3 Virtual chromoendoscopy, 3, 16, 23, 25 Virtual magnified ileoscopy, 5 W Wireless capsule endoscopy, 48 Wireless Capsule, 48 Y Yersinia enterocolitica, 42 Z Zoom, 22, 24 Zoom endoscopy, 22