Hernia Repair Sequelae

Volker Schumpelick Robert J. Fitzgibbons (Eds.) Hernia Repair Sequelae

Volker Schumpelick Robert J. Fitzgibbons (Eds.)

Hernia Repair Sequelae In Collaboration with Joachim Conze

With 236 Figures and 97 Tables

1 23

Prof. Dr. Volker Schumpelick

Prof. Dr. Robert J. Fitzgibbons

Chirurgische Klinik Universitätsklinikum Aachen Pauwelsstraße 30 52074 Aachen Germany e-mail: [email protected]

Department of Surgery Creighton University 601 North 30th Street Suite 3740 Omaha, NE 68131 USA e-mail: [email protected]

ISBN 978-3-642-04552-3 Springer-Verlag Berlin Heidelberg New York Bibliografische Information der Deutschen Bibliothek The Deutsche Bibliothek lists this publication in Deutsche Nationalbibliographie; detailed bibliographic data is available in the internet at http://dnb.ddb.de. 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 microfilms 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 German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable to prosecution under the German Copyright Law. Springer Medizin Springer-Verlag GmbH ein Unternehmen von Springer Science+Business Media springer.de © Springer-Verlag Berlin Heidelberg 2010 The use of general descriptive names, registered names, trademarks, etc. in this publications 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.

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5135 – 5 4 3 2 1 0

V

Preface At the last Suvretta meeting in 2006 on recurrent hernia prevention and treatment, we demonstrated that with the wide range of available techniques, materials, and meshes at our disposal today, an experienced hernia surgeon will be able to prevent or at least treat a recurrent hernia. But whereas recurrences can be treated successfully in most cases, some other hernia repair sequelae can result in severe, sometimes untreatable problems, e.g. pain, infection, adhesion, or infertility. That was the reason to focus the 5th Suvretta meeting in 2008 on hernia repair sequelae. We are convinced that such sequelae can be a more serious problem for the patient than the mostly treatable recurrent hernia. Therefore, it was appropriate to focus the 5th Suvretta meeting on these longterm problems. During a four-day meeting, we discussed all technical aspects of the various operations and materials to generate a consensus concerning the best techniques and meshes. We explored methods to improve surgical techniques to look into the multifactorial causes of post hernia repair sequelae. In the seclusion of the Swiss plateau valley we had a perfect setting to discuss these important hernia repair problems in detail with the top hernia specialists in the world. With this book, the results of this exceptional 5th Suvretta meeting have been made accessible for every surgeon who is interested in hernia surgery and its sequelae. V. Schumpelick

VII

List of First Authors Alfieri, S.

Bachman, S. L.

Champault, G. G.

Department of Digestive Surgery Catholic University of Sacred Heart Largo Agostino Gemelli 8 00168 Rome Italy [email protected]

University of Missouri Department of Surgery Missouri Hernia Institute University of Missouri–Columbia 414 McHaney Hall Columbia, MO 65211 USA

Paris University XIII – Medical School »Léonard de Vinci« Department of Digestive Surgery University Hospital Jean Verdier Avenue du 14 Juillet 93140 Bondy France [email protected]

Amid, P. K. Department of Surgery David Geffen School of Medicine at UCLA Lichtenstein Hernia Institute at UCLA 1260 15th Street, Suite 1200 Santa Monica, CA 90404 USA [email protected]

Bellows, C. Associate Professor of Surgery Chief, General Surgery Director of Surgical Research General and Laparoscopic Surgery Tulane University New Orleans, LA USA

Chowbey, P. K. Minimal Access, Metabolic and Bariatric Surgery Centre Sir Ganga Ram Hospital Room No. 200 (IInd floor) New Delhi 110060 India [email protected]

Berger, D. Arlt, G. D. Department of Surgery Park-Klinik Weissensee Schönstrasse 80 13086 Berlin Germany [email protected]

Department of Surgery Stadtklinik Balgerstrasse 50 76532 Baden-Baden Germany [email protected]

Conze, J. Department of Surgery University Hospital RWTH Pauwelsstrasse 30 52074 Aachen Germany [email protected]

Binnebösel, M. Aufenacker, T. J. Department of Surgery (C22) Canisius Wilhelmina Ziekenhuis (CWZ) Postbus 9015 6500 GS Nijmegen The Netherlands [email protected]

Aydede, H. Associate Professor of Surgery Celal Bayar University Medical Faculty Department of Surgery Manisa Turkey [email protected]

Department of Surgery RWTH Aachen University Hospital Pauwelsstrasse 30 52074 Aachen Germany [email protected]

Demirer, S. D. Ankara University School of Medicine Department of Surgery Ankara Turkey [email protected]

Bringman, S. Clintec, Karolinska Institutet Stockholm, Sweden Departments of Surgery, Södertälje Hospital Södertälje Sweden [email protected]

Deysine, M. Professor of Surgery Winthrop University Hospital Mineola, NY USA [email protected]

VIII

List of First Authors

Diaz, J. J., Jr.

Flament, J. B.

Hegarty, D.

Division of Trauma and Surgical Critical Care Department of Surgery Vanderbilt University Medical Center Nashville, TN USA [email protected]

Department of Surgery Faculty of Medicine University of Reims ChampagneArdenne General Surgery Service Hôpital Robert Debré Rue Serge Kochman 51100 Reims France [email protected]

Department of Anaesthesia, Intensive Care & Pain Medicine Cork University Hospital Cork Ireland [email protected]

Dilek, O. N. Professor of General Surgery School of Medicine Kocatepe University PK:70 03100 Afyonkarahisar Turkey [email protected]

Falagas, M. E. Department of Medicine, Henry Dunant Hospital, Athens, Greece Department of Medicine, Tufts University School of Medicine, Boston, MA, USA Alfa Institute of Biomedical Sciences (AIBS) 9 Neapoleos Street, 151 23 Marousi Athens, Greece [email protected]

Franz, M. G. Associate Professor of Surgery Chief, Minimally Invasive Surgery University of Michigan Department of Surgery 2214F Taubman Center 1500 East Medical Center Drive Ann Arbor, MI 48109 USA [email protected]

Goldenberg, A. Associate Professor Department of Surgery Federal University of Sao Paulo Brazil [email protected]

Gryska, P. vR. Fawole, A. S. Department of Academic Surgery St. James’s University Hospital Beckett Street Leeds LS9 7TF UK [email protected]

Tufts University School of Medicine Boston, MA Department of Surgery Newton-Wellesley Hospital Suite 365, 2000 Washington Street Newton, MA 0246 USA [email protected]

Hansson, B. Department of Surgery Canisius Wilhelmina Hospital Nijmegen The Netherlands

Honigsberg, E. Mount Sinai Medical Center 1010 5th Avenue New York, NY 10028 USA

Hopf, H. W. Department of Anesthesiology, University of Utah Medical Director, Urban Central Region Wound Care Services LDS Hospital 8th Avenue and C Street Salt Lake City, UT 84132 USA [email protected]

Jansen, M. Department of Surgery University Hospital RWTH Aachen Pauwelsstrasse 30 52074 Aachen Germany [email protected]

Jansen, P. L. Department of Surgery University Hospital RWTH Aachen Pauwelsstrasse 30 52074 Aachen Germany [email protected]

IX List of First Authors

Junge, K.

Kolbe, T.

Montgomery, A.

Department of Surgery Technical University of Aachen Pauwelsstrasse 30, 52057 Aachen Germany [email protected]

Biomodels Austria, University of Veterinary Medicine Veterinärplatz 1 1210 Vienna Austria [email protected]

Department of Surgery Malmö University Hospital 20502 Malmö Sweden [email protected]

Kaemmer, D.

Kukleta, J. F.

Department of Surgery RWTH Aachen Pauwelsstr. 30 52074 Aachen Germany [email protected]

Klinik Im Park Seestrasse 220 8027 Zurich Switzerland [email protected]

Morales-Conde, S.

Muschaweck, U. Kurzer, M.

Kavvadias, T. Department of Obstetrics and Gynaecology Lucerne Cantonal Hospital Lucerne Switzerland

Kehlet, H. Section for Surgical Pathophysiology 4074 Rigshospitalet Copenhagen University Blegdamsvej 9 2100 Copenhagen Denmark [email protected]

Klinge, U. Institute for Applied Medical Engineering Helmholtz Institute for Applied Medical Technology RWTH Aachen University Pauwelsstraße 20-30 52074 Aachen Germany [email protected]

University Hospital Virgen del Rocío. Betis-65, 1º 41010 Sevilla Spain [email protected]

British Hernia Centre 87 Watford Way London NW4 4RS UK [email protected]

Hernienzentrum Dr. Muschaweck – München Arabellastrasse 5 81925 Munich Germany [email protected]

Lammers, B. J.

Neumayer, L.

Department for Colorectal and Hernia Surgery Lukaskrankenhaus Neuss Neuss Germany [email protected]

Professor of Surgery Department of Surgery University of Utah Salt Lake City VA Healthcare System 1950 Circle of Hope Room 6540 Salt Lake City, UT 84132 USA [email protected]

Matthews, B. D. Chief, Section of Minimally Invasive Surgery Department of Surgery Washington University School of Medicine 660 S. Euclid Ave., Campus Box 8109 St. Louis, MO 63110 USA [email protected]

Nordin, P. Head of the Swedish Hernia Register Department of Surgery Östersund Hospital 831 83 Östersund Sweden [email protected]

Otto, J. Miserez, M. Department of Abdominal Surgery University Hospitals Herestraat 49 3000 Leuven Belgium [email protected]

Department of Surgery University Hospital RWTH Aachen Pauwelsstrasse 30 52074 Aachen Germany [email protected]

X

List of First Authors

Page, B. P.

Schug-Paß, C.

Stroh, C.

University Department of Surgery Western Infirmary Glasgow G11 6NT Scotland [email protected]

Department of Surgery Center for Minimally Invasive Surgery Vivantes Hospital Spandau Neue Bergstrasse 6 13585 Berlin Germany [email protected]

Department of General, Abdominal and Paediatric Surgery Municipal Hospital (Teaching Hospital of the Friedrich-Schiller University at Jena, Germany) Strasse des Friedens 122 07548 Gera Germany [email protected]

Pascual, G. Department of Medical Specialities Alcalá University Networking Research Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BNN) Madrid Spain

Peiper, C. Surgical Clinic Evangelisches Krankenhaus Werler Strasse 110 58455 Hamm Germany [email protected]

Penkert, G. Friederikenstift Hannover Department of Neurosurgery Humboldtstrasse 5 30169 Hannover Germany [email protected]

Read, R. C. Emeritus Professor of Surgery 304 Potomac Street Rockville, MD 20850 USA [email protected]

Schippers, E. Surgical Clinic Department of General and Visceral Surgery Juliusspital Juliuspromenade 19 97070 Würzburg Germany [email protected]

Schumpelick, V. Department of Surgery University Hospital RWTH Pauwelsstrasse 30 52074 Aachen Germany [email protected]

Simons, M. P. Department of Surgery Onze Lieve Vrouwe Gasthuis Postbus 95500 1090 HM Amsterdam The Netherlands [email protected]

Smeds, S. The Sergel Clinic Department of Clinical and Experimental Medicine Faculty of Health Sciences University Hospital Linköping University 58185 Linköping Sweden [email protected]

Stanton-Hicks, M. Vice Chairman, Anesthesiology Institute Consulting Staff, CCF Shaker Children’s Pain Rehabilitation Cleveland Clinic Pain Management Department 9500 Euclid Avenue – C-25 Cleveland, OH 44195 USA [email protected]

Stumpf, M. Department of Surgery RWTH Aachen Pauwelsstrasse 30 52074 Aachen Germany michale.stumpf@ klinikum-pforzheim.de

van der Kolk, B. M. Department of Surgery, Division of Abdominal Surgery Radboud University Nijmegen Medical Center Nijmegen The Netherlands

Witkowski, P. Department of Surgery Division of Abdominal Organ Transplantation Columbia University 177 Fort Washington Ave, 7HS, Room 200C New York, NY 10032 USA [email protected]

XI

Contents 15

I Risk for the Spermatic Cord 16 17 1 2

3

4 5 6 7

8

9 10

Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion? . . . . . . . . . . 3 The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model– Preliminary Results . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats . . . . . . . . . . . . . . . . . 29 The Effects of a Mesh Bioprosthesis on the Spermatic Cord Structures . . . . . . . . . . . . . . 39 Influence of Prosthetic Implants on Male Fertility in Rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair . . . . . . . . . . . . . . . . . . . . . . 57 Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like? . . . . . . . . . 65 Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review . . . . . . . . . . . . . . 71

18

19

III 20

21 22

23

24

II

Risk for Infection 25

11 12

13 14

Mesh Infection Following Hernia Repair: A Frequent Problem? . . . . . . . . . . . . . . . . . . . . . . . 79 Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Mesh-Related Infections After Hernia Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .103

Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh . . . . . . .113 Mesh Infection–Therapeutic Options . . . . . . .119 Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery? . . . . . . . . . . . . . . . . . . . . . . . . . . . .125 Infection Control in a Hernia Clinic: 24-Year Results of Aseptic and Antiseptic Measure Implementation in 4,620 »Clean Cases« Based on Up-To-Date Microbiological Research . . . . . . . . . . . . . . . . . . . . . . . .135 Components Separation Technique: Pros and Cons . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143

26 27

28 29

Risk for Pain

Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair: A Reflection of Both Individual Pain Propensity and Surgical Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . .155 Chronic Pain After Inguinal Hernia Repair . . .163 What Do We Know About the Pathophysiology and Pathology of Neuropathic Pain? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .169 Surgical Trauma of Nerves–Causes of Neuropathic Pain, Classification, and Options in Surgical Therapy . . . . . . . . . . . . . . . .177 Risks for Pain–Neuropathic Pain: How Should We Handle the Nerves? . . . . . . . .185 What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .191 Risk Factors for Chronic Pain After Groin Hernia Surgery . . . . . . . . . . . . . . . . . . . . . .199 Ischemic Inflammatory Response Syndrome as an Alternative Explanation for Postherniorrhaphy Pain . . . . . . . . . . . . . . . . .207 Postoperative CRPS in Inguinal Hernia Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .213 Chronic Pain After Open Mesh Repair of Incisional Hernia . . . . . . . . . . . . . . . . . . . . . . . .221

XII

30 31 32

33

34

35

36

37

38

39

40 41

Contents

Clinical Results After Open Mesh Repair . . . .227 Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair . . . . . . . . . . . . . . . . . . . .233 Effect of Nerve Identification on the Rate of Postoperative Chronic Pain Following Inguinal Hernia Surgery . . . . . . . . . . . . . . . . . . . .239 Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair: A Report from the SMIL Study Group . . . . . . .245 Recurrence or Complication: The Lesser of Two Evils? A Review of Patient-Reported Outcomes from the VA Hernia Trial . . . . . . . . .251 Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique . . . . . . . . . . . . . .257 The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia . . . . . . . . . . . . . . . . . . . . .265 Lightweight Macroporous Mesh vs. Standard Polypropylene Mesh in Lichtenstein Hernioplasty . . . . . . . . . . . . . . . . . .275 Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .279 New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia and Orchialgia . . . . . . . . . . . . . . .287 Surgery for Chronic Inguinal Pain: Neurectomy, Mesh Explantation, or Both? . . . 293 Results of Tailored Therapy for Patients with Chronic Inguinal Pain . . . . . . . . . . . . . . . . .299

47 48

49 50 51 52

V

53

54 55 56

57 58 59

IV 42

43 44 45

46

Risk for Adhesion

Adhesion as a Chronic Inflammatory Problem? Risk for Adhesions, Migration, and Erosions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .305 Biological Tissue Graft: Present Status . . . . . .317 IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis . . . . . . . . . . . . . 323 Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual . . . . . . . . . . . . . . . . . . . . . . .331 Tissue Ingrowth, Adhesion, and Mesh Contraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .345

Effect of Different Mesh Materials on Adhesion Formation . . . . . . . . . . . . . . . . . . . . . . .353 Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature . . . . . . . . . . . . . . . . . . . .365 Porosity and Adhesion in an IPOM Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .375 Benefit of Lightweight and/or Titanium Meshes? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .381 ePTFE Prostheses and Modifications . . . . . . . .393 The Role of Stem Cells in Abdominal Wall Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .401

Risk for Migration and Erosion

Safety and Durability of Prosthetic Repair of the Hiatal Hernia: Lessons Learned from a 15-Year Experience . . . . . . . . . . . . . . . . . . . . . . .413 Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty . . . . . . . . . . . . . . . .421 Complications After Gastric Banding– Results in Germany . . . . . . . . . . . . . . . . . . . . . . . .429 Alloplastic Implants for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse . . . . . . . . . . . . . . . . . . . . . . . . . . . .439 Prophylactic IPOM Mesh To Prevent Parastomal Hernias . . . . . . . . . . . . . . . . . . . . . . . .445 Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications . . . . . . . . . . . . . . . . . .451 Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration and Shrinkage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .457

VI Strategy to Improve Results 60 61

Who Has the Major Role in Hernia Surgery: The Surgeon or the Material? . . . . . . . . . . . . . . .463 Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery with Procedures Adjusted to Individual Patients . . . . . . . . . . . . . . . . . . . . . .467

XIII Contents

VII 62 63

64 65 66 67

68

Pro and Contra

In Support of a Standard Technique for Inguinal Hernia Repair . . . . . . . . . . . . . . . . . . . . .475 In Support of Individual Selection of Technique as Related to the Patient– Improvement by Better Selection of Patients Who Can Be Offered a Less Risky Technique: Groin Hernia . . . . . . . . . . . . . . . . . . .479 In Support of Standard Procedure in Abdominal Hernia Repair . . . . . . . . . . . . . . . . . .485 In Support of Individualized Procedures in Abdominal Wall Hernia Repair . . . . . . . . . . .493 In Support of Standard Procedure in Hiatal Hernia Repair . . . . . . . . . . . . . . . . . . . . . . . .503 Strategy To Improve the Results? In Support of Individualized Procedures in Hiatal Hernia Repair . . . . . . . . . . . . . . . . . . . . .513 Questionnaire . . . . . . . . . . . . . . . . . . . . . . . . . . . . .521 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .525

I

I

Risk for the Spermatic Cord

1

Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion? – 3

2

The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model – 13

3

Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results – 21

4

Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats – 29

5

The Effects of a Mesh Bioprosthesis on the Spermatic Cord Structures – 39

6

Influence of Prosthetic Implants on Male Fertility in Rats – 43

7

What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty? – 49

8

The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair – 57

9

Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like? – 65

10

Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review – 71

1

Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion? O. N. Dilek

4

Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

Introduction

1 The spermatic cord anatomy has been well studied because of its important role in testicular physiology and surgery. The spermatic cord is composed of the vas deferens; testicular vessels, including the testicular artery and veins; autonomous nerves; spermatic muscle; and fascia [1]. Each of these structures can have various effects on testicular perfusion. The testicular arteries arise from the abdominal aorta just below the renal artery and travel in the intermediate stratum of the retroperitoneum to reach the internal inguinal ring and become a component of the spermatic cord [1]. In an intraoperative dissection study of over 100 spermatic cords, Beck et al. identified a single internal spermatic artery in 50% of cases, with two arteries in 30% of spermatic cords and three arteries in 20% [1]. At the internal ring, the vessels are joined by the genital branch of the genitofemoral nerve, the ilioinguinal nerve, the cremasteric artery, the vas deferens, and its artery. The testicular artery branches into an internal artery and an inferior testicular artery and into a capital artery to the head of the epididymis [1]. Human testicular parenchyma receives approximately 9 ml of blood per 100 g of tissue per minute. Silber showed that an interruption of the testicular blood supply may result in testicular atrophy [2]. The spermatic veins (testicular veins) collect the blood from the testis, epididymis, and scrotum. The testicular veins form several highly anastomotic channels that surround the testicular artery as the pampiniform plexus. This arrangement allows countercurrent heat exchange, which cools the blood in the testicular artery [1]. The vascular arrangement in the pampiniform plexus–with the counterflowing artery and veins separated only by the thickness of their vascular wall in some areas– facilitates the exchange of heat and small molecules. For example, testosterone is transported from the vein to the artery via a concentrationlimited passive diffusion process. The countercurrent exchange of heat in the spermatic cord provides blood to the testis, which is a specialized structure that functions optimally at 2–4°C lower than the rectal temperatures in normal men [3, 4]. A loss of the temperature differential is associated

with testicular dysfunction [1, 3]. At the level of the inguinal canal, the vein joins to form two or three channels and then a single vein that drains into the inferior vena cava on the right and the renal vein on the left [1, 5]. The cremasteric muscle is one of the parts of the spermatic cord. When this muscle contracts, the cord is shortened, and the testicle is moved closer up toward the body, a position that provides slightly more warmth to maintain optimal testicular temperature. When cooling is required, the cremasteric muscle relaxes, and the testicle is lowered away from the warm body and is able to cool. This phenomenon is known as the cremasteric reflex [6]. The dartos muscle is a sympathetically innervated dermal muscle layer within the scrotum, distinct from the somatically innervated cremasteric muscle. Abnormalities of dartos and cremasteric muscle innervation may impact testis thermoregulation and spermatogenesis [6]. Autonomous nerves reach the testis accompanying the testicular artery and pampiniform plexus. The vast majority of testicular nerves are sympathetic axons with vasomotor function. They innervate the small vessels supplying clusters of Leydig cells and regulate testicular luteinizing hormone receptors and blood flow [7, 8]. About 10% of people develop some type of hernia during their lifetime, and more than 750,000 hernia operations are performed in the United States each year. Hernias are seven times more common in males than in females [9]. Abramson et al. reported that the overall current risk for a male to have an inguinal hernia is 18%, and the lifetime risk is 24% [10]. Anatomically, a close relation exists between the spermatic cord and inguinal hernias. Inguinal hernias can carry the risk of ischemia of the testis by intermittent mechanical compression (pressure) on the testicular vessels [11, 12]. In some reports, color Doppler ultrasonography showed that, preoperatively, the sonographic resistive index (RI) was significantly elevated in the affected (hernia) side compared with the normal side [13]. On the other hand, Muñoz Sánchez et al. concluded that uncomplicated inguinal hernias cause no significant alterations in the arterial circulation of the testicle [14].

5 Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

The laparoscopic totally extraperitoneal preperitoneal (TEP) hernia repair technique, which is based on the concept of tension-free high ligation of the sac, has become widely popular in surgical practice [15–18]. Lichtenstein hernia repair (LHR) is one of the most comfortable effective methods of inguinal hernia repair, and it has similarities with TEP because of the prosthetic mesh used [19]. Despite the frequency of open and laparoscopic herniorrhaphy, the effects of a hernia and its subsequent repair on testicular perfusion and function are unknown. It is presently unclear what the best method is for reconstructing the deep inguinal ring in hernia surgery with mesh implantation. Testicular dysfunction (atrophy) is one of the most dreaded sequelae of inguinal hernioplasty. However, literature findings show that testicular atrophy occurs in 0–2% of patients after herniorrhaphy [9, 20]. Yavetz et al. reported that among 8,500 patients attending a fertility clinic because of infertility, 565 men (6.65%) reported an incidence of inguinal hernioplasty with or without subsequent atrophy of the testis [21]. The preoperative and postoperative use of color Doppler ultrasound (CDUS) to evaluate the spermatic cord structure and scrotal structure has been well documented in testicular pathologies and hernias [22–24]. CDUS is extremely helpful in all cases to investigate extratesticular vascularization and testicular perfusion, with parameters optimized to display low-flow velocities, including peak systolic velocity (PSV) and end diastolic velocity (EDV). Lefort and colleagues showed that color Doppler examination of the scrotum should include measurement of intratesticular RI, as an elevated RI can be suggestive of ischemia [25]. However, most of these conditions have not been well documented using CDUS after TEP or LHR. We have discussed the previously unreported use of testicular CDUS in patients who underwent TEP or LHR. Damage to the spermatic cord structures, testicular atrophy, and dysfunction levels as a consequence of mesh application are not well known in adults. The purpose of this study was to evaluate the efficacy of prosthetic meshes on testis perfusion and testis volume with Lichtenstein and TEP hernia repair techniques.

1

Materials and Methods In our prospective randomized series of 82 patients, 26 of them (age 24–71 years) fulfilled the inclusion criteria and underwent elective herniorrhaphy for groin hernia [26]. In patients with an American Society of Anesthesiologists (ASA) score of more than II, having a hydrocele and/or a varicocele could alter the testicular function independent of the hernia repair [27, 28]. For this reason, patients with the following conditions were excluded from the study: hernia types Ia, IIb, III, or IV according to the Nyhus classification [16, 29]; ASA scores of III, IV, or V; or hydrocele and/or varicocele. Other exclusion criteria were recurrence, conversion to an open procedure, or the inability to provide informed consent. Scrotal hernias or large hernias are predisposing factors for testicular atrophy (type IIb or larger), and very small hernias (type Ia) are not suitable for TEP or LHR methods. Thus, giant scrotal hernias were also excluded in our study [26]. Each patient was randomly assigned to one of two groups: TEP (n=13, mean age 46.7±1.6 years) or LHR (n=13, mean age 54.2±2.7 years). Six of the patients had bilateral hernias (n=3 for each group). CDUS of the testes was performed on all patients the day before operation and 3 months after operation. The scrotum was examined with a linear (5 MHz) transducer (ATL Ultramark 9, USA). Color Doppler settings were optimized to detect slow flow, with the highest color gain setting allowing an acceptable signal-to-noise ratio, the lowest wall filter, and the lowest velocity scale. Ultrasound of the scrotum was performed in the supine position, and the patient was asked to hold the penis suprapubically. Blood flow parameters of the spermatic artery were evaluated and noted as PSV, EDV, and calculated RI. The investigation protocol was approved by the ethics committee of our institution. Patient groups were compared with each other, and the nonoperated side was compared with the operated side. Kruskal–Wallis and Mann–Whitney U–tests were used to evaluate the differences. A two-sided p-value <0.05 was considered significant [26].

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Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

Results

1 In our series, the mean patient age was 49.6±1.7 (range 24–71) years; in the LHR group, 54.2±2.6 (range 26–71) years; and in the TEP group, 46.7±1.7 (range 32–62) years. We found no significant changes in blood flow parameters (PSV, EDV, RI) when comparing the two groups preoperatively and postoperatively (⊡ Tables 1.1 and 1.2). Also, there were no significant changes in the blood flow parameters when the TEP and LHR groups were compared with each other [26].

⊡ Table 1.1. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) measurements in the totally extraperitoneal group (NS not significant) Preoperative

Postoperative

PSV

18.18±1.03

17.84±1.11

EDV

6.68±0.48

6.07±0.37

RI

0.62±0.017

0.63±0.018

p

NS

⊡ Table 1.2. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) measurements in the Lichtenstein repair group (NS not significant)

Discussion All inguinal hernia repair techniques aim to close the internal ring with a suture or a biomaterial such as polypropylene mesh. Concern has been raised about whether the spermatic cord structures are compromised with these techniques The spermatic cord structures may be exposed to invasive surgical intervention during inguinal hernia reconstruction. Surgical dissection, division, or mechanical trauma to the spermatic artery and veins accounts for serious trophic changes in the testis. Lee et al. have explained that surgical manipulation of the spermatic cord imparts a small but statistically significant morphological change in testicular size without a deleterious effect on testicular development, fertility, or fecundity [20]. Many factors can lead to decreased or interrupted testicular perfusion. In some reports, inguinal hernia may impair testicular blood flow, which may be attributable to the effect of intermittent mechanical compression on the funiculus spermaticus in the inguinal canal [11–13, 25]. Testicular artery and vein injuries, thrombosis of the spermatic vein plexus, and testicular torsion are the major factors influencing testicular perfusion. Furthermore, the implantation of a nonabsorbable polypropylene mesh during hernia repair causes a chronic foreign body reaction involving the surrounding tissue. In cases of inguinal hernia repair using different mesh techniques, the spermatic cord structures are potentially affected by this chronic inflammatory tissue remodeling [30].

Preoperative

Postoperative

PSV

17.30±0.98

17.24±0.78

EDV

5.51±0.29

5.70±0.29

RI

0.65±0.017

0.66±0.014

p

NS

However, many authors have reported that the testes have more vessels than expected. Testicular arterial anatomy has been well studied because of its important role in testicular physiology and testicular surgery. Anatomically, the spermatic artery divides into two branches near the testis. Jarow et al. showed that the frequent early branching of the internal spermatic artery prevents inadvertent interruption of testicular arterial blood flow during operations performed on the spermatic cord within the inguinal canal [31]. The testicular artery penetrates the tunica albuginea at the lower pole, proceeding as the capsular artery. Using CDUS, a transmediastinal artery is visible in the upper third of the testis in 50%. Branches from the capsular artery course through the parenchyma in the testicular septations as afferent arteries and are directed to the gonadal hilum. The testicular veins are not consistently visible with CDUS [23]. Many studies suggest an unknown or alternative (collateral) connection between vessels of the cord and other vessels that supply blood to the testis [14, 32–34]. Zomorrodi and Buhluli explained that they isolated and ligated the spermatic cord at the internal ring of the inguinal canal for transfixation and placed the allografted

7 Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

Thrombosis Ligating /Cutting Hematoma Inflammation Fibrosis

1

Ischemic orchitis Testicular ischemia

Testicular atrophy

kidney in the retroperitoneal position with anastomoses of the iliac vessels, and that mass ligation of the spermatic cord did not lead to any ischemic problems in the follow-up period [33]. Zát’ura et al. concluded that in the great majority of men, the blood supply of the testis is ensured by collateral circulation [34]. It is well known that thrombosis, ligation, and/ or cutting of the spermatic vessels may lead to ischemia, ischemic orchitis, and testicular atrophy (⊡ Fig. 1.1). Ischemic orchitis typically presents 2–3 days after inguinal hernia surgery and can progress to infarction. This ischemic injury is likely due to thrombosis of the venous plexus rather than to iatrogenic arterial injury or inappropriate closure of the inguinal canal [32]. Venous outflow obstruction secondary to thrombosis of the pampiniform plexus can also cause testicular infarction as a result of overzealous dissection of the cord or excessive use of diathermy; it may also be the result of pressure from a large hematoma in the groin [35]. Testicular torsion significantly reduces testicular vascular perfusion. Turner et al. reported that in an experimental study, experimental torsion significantly reduced testicular vascular perfusion. Five minutes after torsion repair, the mean flow values had returned to approximately 70% of the pretorsion values. Testicular torsion significantly reduced the venous plasma testosterone concentrations at both 3 and 30 days after torsion repair. These authors suggest that reperfusion/oxidative stress may play a role in Leydig cell dysfunction, as well as acting directly in germ cell apoptosis [36].

⊡ Fig. 1.1. Ischemic conditions and their relationship to testicular perfusion and testicular atrophy

Testis perfusion can be maintained for a prolonged period in the presence of testicular torsion. Anatomical variability may account for differences in the duration of viability of the torsed testis [37]. It is clear that impairment of testicular perfusion can lead to testicular damage (atrophy). Other causes also exist, such as obstruction of the vas deferens, inguinal hematoma, infections, and immunological reactions [21, 38]. For about 25 years, the use of prosthetic materials for repairing inguinal hernias has been routine in general surgery. An estimated 80% of inguinal hernia operations involve placement of a prosthetic mesh to form a »tension-free« herniorrhaphy. The prosthetic mesh induces a chronic foreign body fibroblastic response, creating scar tissue that imparts strength to the floor and leads to fewer recurrences [38]. The use of prosthetic materials for inguinal hernia markedly reduces the recurrence rates, postoperative hospital stay, pain, and discomfort. But the prosthesis frequently adheres to the cord structures in most cases. The disadvantages include local wound complications, technical difficulties in hernia repair, restriction of mobility by the rigid shell (⊡ Fig. 1.2), contraction of the mesh, and complications related to the cord structures, such as varicocele, hydrocele, ischemic orchitis, testicular atrophy, and, finally, infertility [39]. In our study, we aimed to study the effects of the TEP and LHR techniques on testicular circulation [26]. We did not find any significant differences between the techniques regarding blood flow in the testes. Our previous report included

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Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

1

⊡ Fig. 1.2. Prosthetic mesh induces a chronic foreign body reaction involving the surrounding tissue and the spermatic cord structures, which could impair testicular perfusion and lead to testicular atrophy

the same population, and neither TEP nor LHR affected testicular function; TEP did decrease testicular volume, but by normal limits [40]. The influence of the Lichtenstein and Shouldice operations on the cord structures was investigated in a canine model. Similar to our results, no significant differences with regard to testicular volume and blood flow were found between the operation groups or between the preoperative and postoperative results [41, 42]. Many clinical studies have reported similar results in which the choice of either the Lichtenstein or TEP hernia repair technique did not significantly alter testicular function. Patients with inguinal hernia have an elevated testicular vascular resistance, which is reversed after repair. The choice of laparoscopic or open herniorrhaphy did not affect reversal of this surrogate of testicular function [13, 42, 43]. Laparoscopic inguinal hernia repair using suture closure of the internal inguinal ring does not impair testicular perfusion. Advantages of the laparoscopic approach also include its technical ease and the fact that it is an outpatient procedure, the cord structures remain untouched, the type of hernia is obvious, and clear visualization of the anatomy can be achieved [44]. However, some clinical and experimental studies revealed a dense fibroblastic response encompassing the polypropylene mesh that either

trapped or obliterated the testicular vessels and vas deferens [30, 38]. Peiper et al. [45] reported that implantation of a nonabsorbable polypropylene mesh in the inguinal region during hernia repair causes a chronic foreign body reaction involving the surrounding tissue and the spermatic cord structures in pigs. They observed that venous thrombosis of the spermatic veins occurred in five of 15 cases. The mesh repair may also lead to decreases in arterial perfusion, testicular temperature, and the rate of regular spermatogenesis in seminiferous tubules. Therefore, they recommend strict indications for implanting a prosthetic mesh during inguinal hernia repair [45]. Prosthetic meshes can contract by 20–75% of their original size within a year after implantation in the inguinal region. Taylor et al. set out to determine whether this contraction has any effect on testicular or femoral vessel blood flow following open or laparoscopic hernia repair. They found that mesh contraction following inguinal hernioplasty does not adversely affect the testis or femoral vessels and that mesh can be used safely for both anterior and preperitoneal approaches [46]. With Doppler, the flow in the spermatic artery and testicular artery and its branches is of low resistance, with a relatively broad systolic part and holodiastolic flow. CDUS enables a definitive diagnosis of ischemia and decreased testicular

9 Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

circulation. A pitfall to remember in the diagnosis is that hypervascularity can occur [47]. Testicular and epididymal swelling along with a slightly decreased echogenicity have been reported to develop in the first hours, although in most cases the hypoechogenicity occurs later, so examining the testis 3 months after the operation seems to be more rational, as was done in our study [48, 49]. There are many clinical and experimental study results concerning whether testicular perfusion is adversely affected. We thought it would be difficult to impair testicular perfusion after hernia repair because of the rich arterial supply and collateral capacity. Arterial input and venous drainage of the testis are assured by many anastomoses that protect it from ischemic injury [50–52]. Careful dissection and preservation of the vessels are important to protect these anastomoses during hernia repair. The idea that deep ring repair that is too tight may cause testicular ischemia is erroneous. There are also many ways to protect testicular perfusion. Surgeons should be trained to repair all inguinal hernias at diagnosis, even if asymptomatic. This treatment practice will decrease and prevent complications such as incarceration and strangulation; moreover, herniorrhaphy becomes more difficult the longer that repair is delayed [9, 11]. Trauma to spermatic cord structures should be minimized and the incidence of testicular atrophy reduced by limiting dissection trauma to the spermatic cord, by never dissecting beyond the pubic tubercle, by leaving distal indirect hernia sacs attached to the cord, and, as in recurrent hernias, by avoiding dissection of the spermatic cord altogether by employing a posterior preperitoneal approach [35]. Preserving the cremasteric muscle fibers and reconstructing the fascia can protect the structures of the spermatic cord from the inflammatory reaction [45]. Overzealous dissection of a distal hernia sac, dislocation of the testis from the scrotum into the wound, and concomitant scrotal surgery should be avoided [50]. Patients considering polypropylene mesh herniorrhaphy need to be carefully advised about potential obstruction and compromise to future fertility in men, especially those of young reproductive age or with a solitary testicle [38].

1

Preperitoneal repairs should be considered for repairs of recurrent hernias, not only to reduce further recurrences but also to avoid testicular complications [53]. Using an intraperitoneal composite mesh onlay and assuring safe fixation with fibrin glue could be an alternative when treating recurrent and complicated inguinal hernias [54]. In conclusion, neither TEP nor LHR affected testicular circulation in our study [26]. The total number of patients in our study was a limitation. It is clear that fine surgical dissection and reconstruction with respect for anatomy and the use of proper prosthetic material could lead to the best results. To be consistent, future animal and clinical studies must be performed in large groups and focus on the use of mesh, which may increase the intensity of the mesh reaction to the cord structures.

References 1. Brooks JD (2007). Anatomy of the lower urinary tract and male genitalia. In: Wein AJ (ed) Campbell–Walsh urology, 9th edn. Saunders Elsevier, China, pp 38–77 2. Silber SJ (2000). Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia. Hum Reprod 15(11):2278–2284 3. Mieusset R, Bujan L, Mansat A, Pontonnier F, Grandjean H (1987). Hyperthermia and human spermatogenesis: enhancement of the inhibitory effect obtained by »artificial cryptorchidism.« Int J Androl10(4):571–580 4. Kurz KR, Goldstein M (1986). Scrotal temperature reflects intratesticular temperature and is lowered by shaving. J Urol 135(2):290–292 5. Mihalache G, Indrei A, Mihalache GD (1996). The vasa vasorum in the veins of the spermatic cord. Rev Med Chir Soc Med Nat Iasi 100(3–4):180–182. [Romanian with English abstract] 6. Yilmaz U, Yang CC, Berger RE (2006). Dartos reflex: a sympathetically mediated scrotal reflex. Muscle Nerve 33(3):363–368 7. Wrobel KH, Abu-Ghali N (1997). Autonomic innervation of the bovine testis. Acta Anat (Basel) 160(1):1–14 8. Schlegel PN, Hardy MP, Goldstein M (2007). Male reproductive physiology. In: Wein AJ (ed) Campbell–Walsh urology, 9th edn. Saunders Elsevier, Philadelphia, pp 577–608 9. Fitzgibbons RJ, Filipi CJ, Quinn TH (2005). Inguinal hernias. In: Brunicardi FC (ed) Schwartz’s principles of surgery, 8th edn. McGraw-Hill, New York, pp 1353–1394 10. Abramson JH, Gofin J, Hopp C, et al. (1978). The epidemiology of inguinal hernia. A survey in western Jerusalem. J Epidemiol Community Health 27:300

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Chapter 1 · Are There Adverse Effects of Herniorrhaphy Techniques on Testicular Perfusion?

11. Hager J, Menardi G (1986). Ischemic damage of the testis as a complication of incarcerated hernia in the infant. Padiatr Padol 21(1):17–24 [German with English abstract] 12. Turgut AT, Ölçücüoğlu E, Turan C, et al. (2007). Preoperative ultrasonographic evaluation of testicular volume and blood flow in patients with inguinal hernias. J Ultrasound Med 26(12):1657–1666 13. Beddy P, Ridgway PF, Geoghegan T, Peirce C, Govender P, Keane FB, Torreggiani WC, Conlon KC (2006). Inguinal hernia repair protects testicular function: a prospective study of open and laparoscopic herniorrhaphy. J Am Coll Surg 203(1):17–23 14. Muñoz Sánchez MJ, Muñoz Fernández L, Prados Olleta N, Vara Thorbeck R (2005). Testicular-epididymal hemodynamics and inguinal hernia. Eur Surg Res 37(4):257–264 15. Stoppa RE, Waarlaumont CR (1989). The preperitoneal approach and prosthetic repair of groin hernia. In: Nyhus LM, Condon RE (eds) Hernia, 3rd edn. Lippincott, Philadelphia 16. Nyhus LM, Condon RE, Harkins HN (1960). Clinical experiences with preperitoneal hernial repair for all types of hernia of the groin, with particular reference to the importance of transversalis fascia analogues. Am J Surg 100:239–244 17. Kingsley D, Vogt DM, Nelson T, et al. (1998). Laparoscopic intraperitoneal onlay inguinal herniorrhaphy. Am J Surg 176:548–553 18. McKernan JB, Laws HL (1993). Laparoscopic repair of inguinal hernia using a totally extraperitoneal prosthetic approach. Surg Endosc 7:26–28 19. Collaboration EH (2000). Laparoscopic compared with open methods of groin hernia repair: systematic review of randomized controlled trials. Br J Surg 87:860–867 20. Lee SL, DuBois JJ, Rishi M (2000). Testicular damage after surgical groin exploration for elective herniorrhaphy. J Pediatr Surg 35(2):327–330 21. Yavetz H, Harash B, Yogev L, Homonnai ZT, Paz G (1991). Fertility of men following inguinal hernia repair. Andrologia 23(6):443–446 22. Ponka JL (1980). Early and late postoperative complications and their management. In: Ponka JL (ed) Hernias of the abdominal wall. Saunders, Philadelphia, pp 605–618 23. Oyen RH (2002). Scrotal ultrasound. In: Baert AL (ed) Syllabus ultrasound. Springer, Berlin, pp 280–295 24. Hostman WG (1997). Scrotal imaging. Uroradiology 24:653–671 25. Lefort C, Thoumas D, Badachi Y, Gobet F, Pfister C, Dacher JN, Benozio M (2001). Ischemic orchiditis: review of 5 cases diagnosed by color Doppler ultrasonography. J Radiol 82(7):839–842 26. Dilek ON, Yücel A, Akbulut G, Değirmenci B (2005). Are there adverse effects of herniorrhaphy techniques on testicular perfusion? Evaluation by color Doppler ultrasonography. Urol Int 75:167–169 27. Segenreich E, Israilov SR, Shmueli J, Niv E, Servadio C (1997). Correlation between semen parameters and ret-

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rograde flow into the pampiniform plexus before and after varicocelectomy. Eur Urol 32(3):310–314 Sigman M, Jarow JP (1997). Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles. J Urol 158(2):605–607 Wantz GE (1986). Testicular atrophy as a sequela of inguinal hernioplasty. Int Surg 71:159–163 Peiper C, Junge K, Klinge U, Strehlau E, Krones C, Ottinger A, Schumpelick V (2005). The influence of inguinal mesh repair on the spermatic cord: a pilot study in the rabbit. J Invest Surg 18(5):273–278 Jarow JP, Ogle A, Kaspar J, Hopkins M (1992). Testicular artery ramification within the inguinal canal. J Urol 147(5):1290–1292 Moore JB, Hasenboehler EA (2007). Orchiectomy as a result of ischemic orchitis after laparoscopic inguinal hernia repair: case report of a rare complication. Patient Saf Surg 1(1):3 Zomorrodi A, Buhluli A (2008). Viable testis after retroperitoneal mass cord ligation in internal ring of inguinal canal in 15 kidney recipients: five years of experience. Transplant Proc 40(1):208–209 Zát’ura F, Student V, Fiala R, Vrtal R (1997). Personal experience with peroperative study of testicular blood flow in laparoscopic surgery of varicocele. Rozhl Chir 76(9):419– 420 Wantz GE (1982). Testicular atrophy as a risk inguinal hernioplasty. Surg Gynecol Obstet 154(4):570–571 Turner TT, Bang HJ, Lysiak JJ (2005). Experimental testicular torsion: reperfusion blood flow and subsequent testicular venous plasma testosterone concentrations. Urology 65(2):390–394 Bentley DF, Ricchiuti DJ, Nasrallah PF, McMahon DR (2004). Spermatic cord torsion with preserved testis perfusion: initial anatomical observations. J Urol 172(6 Pt 1):2373–2376 Shin D, Lipshultz LI, Goldstein M, et al (2005). Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction: a preventable cause of obstructive azoospermia. Ann Surg 241(4):553–558 Homonnai ZT, Fainman N, Paz GF, David MP (1980). Testicular function after herniotomy. Herniotomy and fertility. Andrologia 12:115–120 Akbulut G, Serteser M, Yücel A, et al. (2003). Can laparoscopic hernia repair alter function and volume of testis? Randomized clinical trial. Surg Laparosc Endosc Percutan Tech 13:377–381 Uzzo RG, Lemack GE, Morrissey KP, Goldstein M (1999). The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 161:1344–1349 Ersin S, Aydin U, Makay O, et al. (2006). Is testicular perfusion influenced during laparoscopic inguinal hernia surgery? Surg Endosc 20(4):685–689 Zieren J, Beyersdorff D, Beier KM, Müller JM (2001). Sexual function and testicular perfusion after inguinal hernia repair with mesh. Am J Surg 181(3):204–206

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44. Schier F (2006). Laparoscopic inguinal hernia repair–a prospective personal series of 542 children. J Pediatr Surg 41(6):1081–1084 45. Peiper C, Junge K, Klinge U, Strehlau E, Ottinger A, Schumpelick V (2006). Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and the rabbit. Hernia 10(1):7–12 46. Taylor SG, Hair A, Baxter GM, O’Dwyer PJ (2001). Does contraction of mesh following tension free hernioplasty effect testicular or femoral vessel blood flow? Hernia 5(1):13–15 47. Leung WYM, Poon M, Fan TW, et al. (1999): Testicular volume of boys after inguinal herniotomy: combined clinical and radiological follow-up. Pediatr Surg Int 15: 40–41 48. Oyen RH (2002). Scrotal ultrasound. In: Baert AL (ed) Syllabus ultrasound. Springer, Berlin, pp 280–295 49. Hostman WG (1997). Scrotal imaging. Uroradiology 24:653-671 50. Reid I, Devlin HB (1994). Testicular atrophy as a consequence of inguinal hernia repair. Br J Surg 81:91–93 51. Fong Y, Wantz GE (1992). Prevention of ischemic orchitis during inguinal hernioplasty: experience with 6454 hernioplasties in male patients. Surg Gynecol Obstet 174:399–402 52. Koontz AR (1965). Atrophy of the testicle as a surgical risk. Surg Gynecol Obstet 120:511–513 53. Wantz GE (1993). Testicular atrophy and chronic residual neuralgia as risks of inguinal hernioplasty. Surg Clin North Am 73(3):571–581 54. Olmi S, Scaini A, Erba L, Bertolini A, Croce E (2007). Laparoscopic repair of inguinal hernias using an intraperitoneal onlay mesh technique and a Parietex composite mesh fixed with fibrin glue (Tissucol). Personal technique and preliminary results. Surg Endosc 21(11):1961–1964

Discussion Fitzgibbons: Your technique with color Doppler is very good, investigating the circulation of the testis. How good is it for testing the venous? Dilek: I don’t have additional information about that because this part of the study was done by the radiologist. Smeds: At first, do you have an idea if there is a change of the testicular temperature, and second, do you know if there is a connection between decrease of temperature and sperm production? Dilek: That was not our topic, so I can’t give you more information about that. Schumpelick: How can we decide about testicular function that may be influenced by this method if we don’t analyze the function? I mean, temperature is not a function.

1

2

The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model A. Montgomery and F. Berndsen

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Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

Introduction

2

According to the Swedish Hernia Register [1], an estimated 80% of inguinal hernia operations involve placement of a polypropylene mesh, with a majority performed as a Lichtenstein procedure. The Lichtenstein technique is regarded as the gold standard in Sweden; this is probably in accordance with most other countries. A prosthetic mesh induces a chronic foreign body reaction with fibroblastic ingrowth into the mesh and subsequent scar plate formation. This is believed to reinforce the abdominal wall and thereby decrease the risk of recurrence by 50–70% [2]. The foreign body reaction leads to chronic inflammation, which can cause retraction of the mesh area and shrinkage of the scar plate. As a result, tension can be put to the anchoring points of the mesh, which might cause chronic pain. Patients might also have individual reactions to meshes with different properties. These might be some of the factors causing chronic pain in up to 15–30% of patients operated on for inguinal hernias in whom mesh is used [3, 4]. It has been suggested that the foreign body reaction is proportionate to the weight and structure of the mesh and that commonly used meshes contain too much material, producing an exaggerated response [5, 6]. To minimize these effects, composite meshes have been introduced that contain one absorbable and one nonabsorbable part. By the use of composite meshes, the reinforcement and manageability properties desired at operation and in the early phase can thereby be satisfied together with a reduction in the total amount of mesh left permanently in the patient. Problems other than chronic pain that might be associated with chronic inflammation caused by mesh include sexual dysfunction and infertility. These problems are not well understood. Infertility can be related to the handling of the spermatic cord during inguinal herniorrhaphy. Injury to the vas as well as the spermatic vessels can result in infertility. Ischemic injury to the testicle that eventually leads to atrophy is reported to occur in about 0.5% of patients having primary hernia repair and 5% with recurrent hernia repairs [7, 8]. Another potential mechanism for infertility is a foreign

body reaction resulting from the use of mesh that comes into contact with the spermatic cord. Bilateral hernia surgery in children is a known risk factor for infertility [9]. In men investigated for infertility, 6.4% are reported to have had an iatrogenic injury to the vas after hernia surgery [10]. To try to minimize some of the inflammatory effects, a composite mesh has been introduced that contains 61% absorbable (polyglactin) and 39% nonabsorbable material (polypropylene; Vypro II). The total weight of polypropylene is 32 g/m2. The aim of this study was to compare a heavyweight polypropylene mesh with a lightweight composite mesh to note the effect on spermatic cord structures and testosterone production in an experimental setting.

Materials and Methods Thirty male Sprague Dawley rats were randomly divided into three groups. A 3-cm long incision was made in the groin, and the spermatic cord was exposed and dissected free. The cremaster muscle was split but not divided. In group I, a suture repair was performed using 5.0 polypropylene sutures (Prolene, Ethicon, Somerville, NJ, USA) in the transversalis fascia, imitating open suture repair. In group II, a 2×3.5-cm heavyweight polypropylene mesh (Prolene, Ethicon, Somerville, NJ, USA) was placed, imitating the Lichtenstein repair. A slit was made in the mesh for the spermatic cord. The mesh was fixed with 5.0 Prolene sutures, and the tails were approximated with one suture. In group III, a large-pore lightweight polypropylene/polyglactin composite mesh, Vypro II (Ethicon, Norderstedt, Germany), was placed as in group II. After 90 days, vasography was performed, and blood samples were taken from the venous plexus of the spermatic cord on both sides. Analysis of stestosterone from the spermatic veins was carried out using competitive radioimmunoassay. Testicles from both sides were weighed. The inguinal areas on both sides were dissected en bloc, including the spermatic cord, the mesh, and the underlying abdominal wall. Light microscopy was performed

2

15 Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

for a cross-section of specimen obtained from the middle of the 3-cm long sample stained with hematoxylin–eosin and van Gieson’s stain. Inflammation and fibrosis were graded separately using a scale from 0 to 3. The sections of the spermatic cord were captured using a camera, and the images were reduced in pixels to obtain a cross-sectional area of the vas deferens from both sides. Continuous and nonparametric data were calculated as the median (interquartile range) and compared using the Mann–Whitney U-test. For comparing operated and control sides, the Wilcoxon signed-rank test was used.

vas deferens in all animals on both sides (⊡ Fig. 2.1). There was no significant difference in testicular weight between the groups or between sides. There was no difference in s-testosterone values between the operated and the control sides in group I or II. However, in group III, s-testosterone values were significantly lower in the operated compared with the control side (⊡ Table. 2.1). There was no significant difference in vas deferens cross-sectional area between the operated and the control side in group I or II, but a difference was seen in group III.

Group I (Suture Repair) vs. Groups II and III (Mesh Repairs)

Results All rats survived the 90-day study period with no wound complications. Vasography revealed patent

There was no difference in s-testosterone from the spermatic vein between the operated sides or between the control sides between the groups (⊡ Table. 2.2). The median grade of inflammation and fibrosis was significant lower in the suture repair group compared with the mesh groups. The inflammation in group I was concentrated around the sutures; no inflammation was seen in sections not including sutures. There was no difference in the cross-sectional area of the vas deferens between the groups.

Group II (Prolene Mesh) vs. Group III (Vypro II Mesh) There was no difference in s-testosterone from the spermatic vein between the operated and the control side between the groups (⊡ Table. 2.3). There

⊡ Fig. 2.1. Vasography showing patent vas deferens

⊡ Table 2.1. Testicular weight, s-testosterone, and vas deferens diameter: operated vs. control side (medians are presented) Group I: suture repair

Group II: Prolene mesh

Group III: Vypro II mesh

Operated side

Control side

p

Operated side

Control side

p

Operated side

Control side

p

s-testosterone (nmol/l)

127

179

0.176

202

260

0.214

83

127

0.008

Vas deferens cross-sectional area (pixels)

157

183

0.753

109

173

0.260

158

187

0.022

16

Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

⊡ Table 2.2. Group I (suture repair) vs. groups II and III (mesh repairs); medians are presented

2

Group I: suture repair

Groups II and III: mesh repairs

p

Testosterone (nmol/l): Operated side Control side

127 179

176 174

0.849 0.935

Inflammation: grade 0–3

1.0 (0–1.3)

2.0 (2.0–2.0)

0.001

Fibrosis: grade 0–3

1.0 (0.8–2.0)

2.0 (1.0–2.5)

0.046

Vas deferens cross-sectional area: Operated side Control side

157 183

152 176

0.400 0.809

⊡ Table 2.3. Group II (Prolene mesh) vs. group III (Vypro II mesh); medians are presented Group II: Prolene mesh

Group III: Vypro II mesh

p

Testosterone (nmol/l): Operated side Control side

202 260

83 127

0.052 0.123

Inflammation: grade 0–3

2.0 (1.5–2.0)

2.0 (2.0–2.0)

0.481

Fibrosis: grade 0–3

2.0 (1.8–2.0)

2.0 (1.0–3.0)

0.696

Vas deferens cross-sectional area: Operated side Control side

109 173

173 187

0.143 0.243

was no difference in the grade of inflammation or fibrosis between the groups. In both groups the inflammation was chronic, with histiocytes concentrated around the mesh material. Giant cells were, however, more prominent in group III (Vypro II), and remaining polyglactin fibres were observed. There was no difference in the cross-sectional area of the vas deferens between the groups.

Conclusion Vasography revealed a patent vas in all animals. The only effects on the cord structures in a rat model were impaired s-testosterone production and a reduced cross-sectional area of the vas after the use of a low-weight composite mesh compared with the control side. This was not demonstrated in the suture repair or heavy polypropylene mesh

groups. No statistical difference in inflammation or fibrosis was seen between heavyweight polypropylene mesh and the low-weight composite mesh. Remaining polyglactin was observed in the lowweight composite mesh group after 90 days.

Discussion Polypropylene meshes have been used in hernia surgery for decades, but their use has increased dramatically the last 10 years. A Cochrane metaanalysis comparing open mesh repairs and conventional repairs revealed a decreased risk of recurrence by 50–75% if mesh were used [2]. The connection between childhood vas injury in inguinal hernia repair has been documented [9]. In adult inguinal hernia surgery, this connection has not been thoroughly studied. This might be of

17 Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

clinical importance because almost 30% of the patients are operated on for bilateral hernias. There could be an injury to the duct structures by dissection, but theoretically, a foreign body reaction around the mesh could also affect the spermatic cord structures because the mesh lies in contact with the spermatic cord. Interest in the latter situation has increased over the last years, and experimental studies have now been performed on dogs, pigs, rabbits, and rats. Uzzo et al. were the first to compare heavyweight polypropylene mesh to conventional (Shouldice) repair in dogs [11]. In their study, all vasograms demonstrated patency, and sperm morphology and motility did not differ between the groups or between the operated and control sides. The patency of the vas was also confirmed in our study. However, Uzzo et al. found morphologic changes of the testis in three out of six animals in the mesh group. No evidence of testicular impairment was seen. They also found a decrease in the cross-sectional diameter of the vas deferens on the operated side compared with the control side in both the suture repair and mesh groups. We reported a cross-sectional reduction only in the Vypro II group and not in the Prolene or the suture repair group. In a later report by Taneli et al., a polypropylene mesh was compared to a sham-operated group in rats [12]. It was concluded that mesh implantation has no effect on testicular hormonal function and only a limited effect on nitric oxide levels, which was not sufficient to cause testicular apoptosis that could lead to infertility. Maciel et al. reported on a study in rats in which bilateral vas deferens dissection was performed and a polypropylene mesh placed on one side [13]. There were no testicular changes, but changes in the vas that caused functional obstruction with dilatation and spermatozoid repression were seen. Two experimental studies from the Aachen group concern findings in pigs and rabbits. The first study consisted of two series, one on pigs and one on rabbits [14]. Preperitoneal Shouldice and Lichtenstein repair were performed, and a polypropylene mesh was used preperitoneally and in a Lichtenstein repair. The mesh repairs resulted in a

2

decrease of arterial perfusion, testicular temperature, and spermatogenesis. The conclusion was that a strict indication for implantation of a prosthetic mesh during hernia repair is recommended. In the second study, low-weight and heavyweight polypropylene mesh were compared in rabbits [15]. Vasography revealed relevant obstructions located at the mesh margins in 50% of the heavyweight and 22% in the lightweight mesh groups after 6 months. This is in contrast to our results, in which all vasograms were normal at 3 months. In another study on rats, Kolbe and Lechner wrapped heavyweight versus low-weight polypropylene mesh around the vas [16]. Fertility was tested and was found to be slightly restricted 4 weeks after surgery in both groups. Some rats in the heavyweight mesh group revealed sperm granulomas due to lesions to the spermatic cord. The conclusion was, however, that neither type of hernioplastic implant indicates a negative influence on male fertility. In a prospective study of 73 patients operated on with the plug-and-patch technique, Zieren et al. measured testicular perfusion and testicular volume preoperatively and at 3 and 6 months postoperatively [17]. No differences between the contralateral side and operated side were seen at follow-up. In the present report, the study period of 90 days was chosen for two reasons. First, the manufacturer claims that the polyglactin part of the Vypro II mesh is totally absorbed in 56–70 days, thus not participating in the inflammation/fibrosis reaction at 90 days. Second, the 90-day period has previously been used and accepted in studies of foreign body reactions [6, 18, 19]. Surprisingly, though, we found remaining polyglactin fibres in the Vypro II specimens after 90 days. This might explain the impaired testosterone production and smaller cross-sectional area of the vas deferens in the Vypro II group compared with the control side. There was, however, no difference in inflammation or fibrosis between the two mesh groups. It is well known that polypropylene mesh induces a foreign body reaction, with chronic inflammation existing even years after implantation [20], but despite millions of mesh implants, only a few reports describe serious adverse effects. Klosterh-

18

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Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

alfen et al. studied the connection between mesh weight and foreign body reaction, and according to their studies, the level of inflammatory response depends on the weight and texture of the mesh material [20]. The large-pore, lightweight mesh (Vypro II), which has only 30% polypropylene compared with standard meshes, has been suggested as leading to less foreign body reaction [21]. Our study did not confirm these findings. It must be stated that animal studies have their limitations, and the results cannot be directly transferred to humans. This type of study, though, is not possible to do in human patients. The overall effect of meshes in reducing the frequency of recurrence, and thereby reducing the frequency of a second, more complicated hernia operation in which the spermatic cord could be in danger by dissection, might well exceed the potential negative effect of the mesh per se.

10.

11.

12.

13.

14.

15.

References 16. 1. The Swedish Hernia Register (Nationellt kvalitetsregister för bråckkirurgi). http://www.svensktbrackregister.se/.2 2. The EU Hernia Trialist Collaboration (2002) Open mesh versus non-mesh repair of groin hernia meta-analysis of randomized trials based on individual patient data. Hernia 6: 130–136 3. Berndsen FH, Petersson U, Arvidsson D, Leijonmarck C-E, Rudberg C, Smedberg S, Montgomery A (2007) Discomfort five years after laparoscopic and Shouldice inguinal hernia repair: a randomised trial with 867 patients. A report from the SMIL study group. Hernia 11(4):307–313 4. Fränneby U, Sandblom G, Nordin P, Nyrén O, Gunnarsson U (2006) Risk factors for long-term pain after hernia surgery. Ann Surg 244(2):212–219 5. Vrijland WW, van der Tol MP, Luijendijk RW, Hop WCJ, Busschbach JJV, de Lange DCD, van Geldere D, Rottier AB, Vegt PA, Ijzermans JNM, Jeekel J (2002) Randomized clinical trial of non-mesh versus mesh repair of primary inguinal hernia. Br J Surg 89:293–297 6. Klosterhalfen B, Klinge U, Schumpelick V(1998) Functional and morphological evaluation of different polypropylene-mesh modifications for abdominal wall repair. Biomaterials 19:2235–2246 7. Wantz GE (1993) Testicular atrophy and chronic residual neuraligia as risk of inguinal hernioplasty. Surg Clin North Am 73:571–581 8. Fitzgibbons RJ (2005) Can we be sure polypropylene mesh causes infertility? Ann Surg 241(4):559–561 9. Matsuda T, Horii Y, Yoshida O (1992) Unilateral obstruction of the vas deferens caused by childhood inguinal

17.

18.

19.

20.

21.

herniorrhaphy in male infertility patients. Fertil Steril 58:609–613 Sheynkin YR, Hendin BN, Schlegel PN, Goldstein M (1999) Microsurgical repair of iatrogenic injury to the vas deferens. J Urol 159:139–141 Uzzo RG, Lemack GE, Morrissey KP, Godstein M (1999 The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 161:1344–1349 Taneli F, Aydede H, Vatansever S, Ulman C, Ari Z, Uyanik BS (2005) The long-term effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis. Cell Biochem Funct 23(3):213–220 Maciel LC, Glina S, Palma PC, Nascimento LF, Netto NR Jr (2007) Histopathological alterations of the vas deferens in rat exposed to polypropylene mesh. BJU Int 100(1):187– 190 Peiper C, Junge K, Klinge U, Strehlau E, Ottinger A, Schumpelick V (2006) Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and the rabbit. Hernia 10(1):7–12 Junge K, Binnebösel M, Rosch R, Ottinger A, Stumpf M, Muhlenburch G, Schumpelick V, Klinge U (2008) Influence of mesh materials on the integrity of the vas deferens following Lichtenstein hernioplasty: an experimental model. Hernia 12(6):621–626 Kolbe T, Lechner W (2007) Influence of hernioplastic implants on male fertility in rats. J Biomed Master Res B Appl Biomater 81(2):435–440 Zieren J, Beyersdorff D, Beier KM, Müller JM (2001) Sexual function and testicular perfusion after inguinal hernia repair with mesh. Am J Surg 181:204–206 Baykal A, Onat D, Rasa K, Renda N, Sayek I (1997) Effects of polyglycolic acid and polypropylene meshes on postoperative adhesion formation in mice. World J Surg 21:579–583 Bellón JM, Contreras LA, Buján J, Palomares D, CarreraSan Martin A (1998) Tissue response to polypropylene meshes used in the repair of abdominal wall defects. Biomaterials 19:669–675 Klosterhalfen B, Klinge U, Hermanns B, Schumpelick V (2000) Pathology of traditional surgical nets for hernia repair after long-term implantation in humans. Chirurg 71:43–51 [German with English abstract] Junge K, Klinge U, Rosch R, Klosterhalfen B, Scumpelick V (2002) Functional and morphologic properties of a modified mesh for inguinal hernia repair. World J Surg 26:1472–1480

)

Discussion Kukleta: Do you think that Vypro II is a good rep-

resentative for a lightweight mesh? The Vypro II has a bigger inflammatory impact than any other lightweight mesh, doesn’t it?

19 Chapter 2 · The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures in a Rat Model

Montgomery: Of course. Indeed, this study was performed in 2003 and published in 2004, and the available meshes at that time were scientifically the most interesting ones. Köckerling: In our various studies with partially resorbable meshes, we always found after the time given by the company some remaining resorbable material in the animals with a high grade of inflammatory reaction around it. We should learn from this to take longer observation periods because the absorption process obviously takes longer than given by the company. Montgomery: That’s why we chose a 90-day interval in our study, but it wasn’t enough. Conze: I just want to make a remark on the animal models used in this context. The diameter of the spermatic cord of small animals differs from human ones, and therefore, the ratio of the diameter of mesh fibers and spermatic cord differs. So the effect of the fibrotic reaction on a very tiny rat vas is much stronger than it might be on a human vas.

2

3

Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results K. Junge, M. Binnebösel, C. Kauffmann, R. Rosch, J. Otto, D. Kämmer, F. Schoth, G. Mühlenbruch, U. Klinge, V. Schumpelick

22

3

Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results

Introduction

Material and Methods

An estimated 75–80% of inguinal hernia operations involve placing a mesh prosthesis, either laparoscopically or using an open technique, to patch the defect in the floor of the inguinal canal. Foreign body reactions, with fibroblastic ingrowth and chronic inflammation, are believed to reinforce the abdominal wall and decrease the risk of recurrence. It has been proven that this foreign body reaction is proportionate to the weight, structure, and polymer of the mesh and that commonly used meshes contain too much material, producing an exaggerated foreign body reaction/tissue response and leading to clinical complications [1–3]. To minimize the foreign body reaction and clinical complications, new types of mesh materials have been introduced that have a decreased amount of material and larger pores, resulting in a nearby physiologic tissue ingrowth [2, 4, 5]. Further improvement of biocompatibility has been achieved using polyvinylidene fluoride (PVDF) as the polymer [3]. PVDF is a polymer with improved textile and biological properties [6]. Compared with polyester, PVDF is more resistant to hydrolysis and degradation. Furthermore, ageing does not increase the stiffness that is evidently seen in polypropylene. Although it has been used in vascular surgery for some years, there have been limited types of surgical meshes until now. Whereas these so-called lightweight, large-pore, and elastic mesh materials are known to show a favourable outcome considering postoperative pain [7–10] compared with conventional heavyweight, small-pore, and stiff mesh materials, just a few experimental studies have focused on the influence of different mesh materials on the integrity of the vas deferens. With the widespread acceptance and ease of placement, mesh repair is being increasingly offered to young patients whose fertility status may well be an issue in the future. To further elucidate the impact of different mesh materials following Lichtenstein hernia repair, an animal study in the pig was conducted to investigate the long-term effect on integrity of the vas deferens and testicular function.

Mesh Materials Two different mesh materials were investigated: a large porous and elastic mesh made of PVDF monofilaments and Marlex, a small-pore, stiff mesh made of polypropylene (PP) monofilaments (⊡ Fig. 3.1).

Animals Six male uncastrated male pigs were housed under conditions of constant light and temperature and received a complete diet of feed and water ad libitum throughout the entire study, which was performed according to the National Institutes of

a

b ⊡ Fig. 3.1. a A large-pore, elastic mesh made of polyvinylidene fluoride monofilaments. b A small-pore, stiff mesh made of polypropylene monofilaments

23 Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure

Health guidelines for the use of laboratory animals. All animals received bilateral Lichtenstein hernia repair (n=12).

Surgical Procedure Operations were carried out under general anaesthesia. Following premedication using 4 mg/ kg azaperone, 44 μg/kg atropine, and 15 mg/kg ketamine intramuscularly, an intravenous catheter was placed into an ear vein. Anaesthesia was induced by injection of 10–15 mg pentobarbital. Anaesthesia was continued by isoflurane/oxygen as well as continuous infusion of fentanyl (45–90 μg/ kg/h). Following anaesthesia, the skin was shaved and disinfected with a povidone–iodine solution. An inguinal incision was performed and the external oblique fascia dissected. Following exploration of the inguinal canal, a Lichtenstein procedure was carried out using a 7×10-cm slitted mesh sample (PVDF mesh on one side, PP mesh on the contralateral side). Mesh samples were fixed at the inguinal ligament and the mesh slit was closed using 4/0 Prolene sutures. Afterwards, the external oblique fascia and skin were closed. No antibiotic treatment was given before or during the experiments. Throughout the whole observation period, all animals were objectively controlled and underwent daily clinical investigation to assess local and systemic complications. Six

3

months after mesh implantation, all animals (n=6) underwent thermographic investigation of the inguinal region and the testes. Thermographic measurements were performed as a parameter of local perfusion using a VarioCAM basic camera (InfraTec, Dresden, Germany). Following measurement of testicular size by ultrasound, the animals were sacrificed for morphologic observations. The abdomen was opened for complete exploration. The intraabdominal part of the vas deferens was dissected 2 cm before entering the inguinal canal at both sides, and 10 ml of x-ray solution was injected for vasography (13.3 g gelatin, 16.6 g Bleimennige =Pb2PbO4, 100 ml water). Following ligation of the vas deferens, the whole inguinal canal–including the mesh sample as well as the testis–was resected and fixed in 10% formaldehyde (⊡ Fig. 3.2).

Assessment of Integrity of the Vas Deferens Integrity of the vas deferens was assessed semiquantitatively using x-ray vasography. Obstructions of the vas deferens were classified as minor (0–25% reduction in lumen diameter), medium (25–75% reduction), or major (>75% reduction) and were examined at the margins of the mesh samples as well as within the mesh area.

Histological Analysis

⊡ Fig. 3.2. Explanted inguinal area including testis with injected x-ray solution

Tissue specimens were embedded in paraffin. Histological investigation was performed on 3-μm sections after haematoxylin and eosin staining. All sections were processed at the same time to reduce internal staining variations. Spermatogenesis as the main testicular function was estimated histologically using the Johnsen score (⊡ Table 3.1) [11]. Immunohistochemistry was done according to the manufacturer’s instructions. For detection of proliferating cells (Ki67), we used mouse monoclonal antibody MIB-1, 1:10, from Dako (Glostrup, Denmark) and rabbit antimouse antibody 1:300 from Dako (Glostrup, Denmark) as secondary antibody. TUNEL histochemistry for the detection of apop-

24

Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results

⊡ Table 3.1. Johnsen score [11] 10

Complete spermatogenesis with many spermatozoa

Thermography Investigating the mean inguinal temperature at the initial incision, no differences were found comparing the PVDF mesh (34.9±0.9°C) with the PP mesh (34.7±0.9°C). Furthermore, no difference was found in testis temperature (PVDF 29.0±1.1°C; PP 29.1±1.1°C; see ⊡ Figs. 3.3 and 3.4).

9

Many spermatozoa present but germinal epithelium

8

Only few spermatozoa (<5–10) present in section

7

No spermatozoa but many spermatids present

6

No spermatozoa and only few spermatids (<5–10) present

Integrity of the Vas Deferens

5

No spermatozoa, no spermatids but several or many spermatocytes present

4

Only few spermatocytes (<5) and no spermatids or spermatozoa present

3

Spermatogonia are the only germ cells present

2

No germ cells but Sertoli cells are present

1

No cells in tubular section

Following explantation, x-ray vasography showed analysable results for all mesh implantations. Overall, relevant obstructions (>75% of lumen diameter; ⊡ Fig. 3.5) were located only at the mesh margins. Whereas four PVDF explants showed no or minor obstructions, one out of six PVDF explants had an obstruction 25–75% of the lumen diameter. The PP mesh group explants were found to have significant obstructions of more than 75% of the lumen diameter in two specimens, as well as obstructions of 25–75% of the lumen diameter in another two. Histologically, no direct infiltration of the mesh fibres into the vas deferens was found. Obstructions were more or less due to compression of the wall of the vas deferens, inducing an inflammatory and fibroblastic reaction in the wall of the vas.

3

totic cells was performed by an in situ apoptosis detection kit (Apoptag, Oncor, cat. no. S7100, Germany). Sections were examined by standard light microscopy (Olympus BX51, Hamburg, Germany). For each sample, five regions within the interface (×400; area 100×100 μm) were captured by a digital camera (Olympus C-3030, Hamburg, Germany). The expression of immunohistochemical parameters was classified by two independent, blinded observers. The extent of staining was graduated as a percentage of positive-stained cells in the specimen (0–100%).

Results Macroscopic Observation The surgical procedure was well tolerated by all animals, and the postoperative period was uneventful. None of the animals developed signs of ischaemic orchitis or testicular atrophy. No differences were seen in testicular volume between the PP (18.9±2.2 cm3) and the PVDF mesh groups (18.1±4.0 cm3).

Histological Analysis Testicular function was estimated histologically. Each testicular sample of 10 seminiferous tubules was classified according to the Johnson score. Following PP mesh implantation, a mean Johnson score of 8.5±0.1 was estimated, which was not significantly different from that for the PVDF mesh samples (8.5±0.3, ⊡ Fig. 3.6). Analysing three out of six mesh explants, each group microscopic investigation of the mesh–hosttissue interface showed typical formation of foreign body granulomas. Investigating the percentage of apoptotic (TUNEL) and proliferating (Ki67) cells, no significant differences were found between the PP (TUNEL 12.7±8.0%; Ki67 7.4±1.8%) and the PVDF mesh samples (TUNEL 3.4±3.3%; Ki67 6.0±2.5%; ⊡ Fig. 3.7).

25 Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure

⊡ Fig. 3.3. Example of temperature measurement using thermography camera

3

⊡ Fig. 3.5. Vasography following mesh implantation; note obstruction of the vas deferens at the margin following polypropylene mesh implantation

⊡ Fig. 3.4. Temperatures (mean ± standard deviation) measured using the thermography system (PP polypropylene, PVDF polyvinylidene fluoride)

⊡ Fig. 3.6. Johnsen score, showing mean ± standard deviation (PP polypropylene, PVDF polyvinylidene fluoride)

26

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Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results

⊡ Fig. 3.7. Percentage (mean ± standard deviation) of (a) proliferating and (b) apoptotic cells at the interface of mesh and the host tissue (PVDF polyvinylidene fluoride, PP polypropylene)

Discussion Obstructive azoospermia is a rare but serious complication following inguinal hernia repair. Although an incidence of iatrogenic perioperative injury to the vas deferens during inguinal hernia repair of 0.3% in adults and 0.8–2.0% in childhood has been described [12], little is known about the long-term effects of different mesh prostheses on the integrity of the vas deferens. Because almost 30% of the patients are operated on for bilateral hernias, and because mesh repair is being increasingly offered to young patients whose fertility status may well be an issue in the future, this item is of major clinical importance. Aside from case reports, just one larger clinical series has been reported. Shin et al. investigated 14 cases of azoospermia secondary to inguinal vasal obstruction related to previous mesh herniorrhaphy [13]. Following open or laparoscopic hernia mesh repair, they reported on nine patients with bilateral obstruction as well as five patients with unilateral obstruction. Surgical exploration revealed a dense fibroblastic response encompassing the polypropylene mesh, with either a trapped or obliterated vas in all patients. The first experimental study investigating this matter was performed by Uzzo et al., comparing six dogs operated with a polypropylene mesh to six dogs operated with conventional (Shouldice) repair [14]. They found a decrease in the cross-sectional diameter of the vas deferens on the operated side compared with the control side in both the suture repair and the mesh groups. Furthermore, mor-

phologic changes of the testis were found in three of six animals in the mesh group. Goldenberg et al. investigated 18 dogs with a follow-up of 60 days and found a chronic inflammatory reaction in 100% on the mesh side, a reduction in spermatogenesis, and a reduction in lumen diameter of the vas deferens on the mesh side [15]. However, studies comparing the effect of different mesh prostheses are rather limited. Peiper et al. investigated spermatic cord perfusion and spermatogenesis in rabbits, comparing Lichtenstein hernia repair using UltraPro (a lightweight, largepore, and elastic mesh) and Marlex (a heavyweight, small-pore, and stiff mesh of polypropylene) with the Shouldice repair [16]. They found a more obvious decrease in spermatic cord perfusion after Marlex mesh repair than after Shouldice repair. In contrast, in our study the analysed temperature (as a parameter of perfusion) showed no differences between the mesh samples in the inguinal region or in the testis. In evaluating spermatogenesis, Peiper’s group noted a decrease in Johnsen score in the seminiferous tubules after Lichtenstein repair independent of the kind of mesh. In our study, a mean Johnsen score of 8.5±0.1 was estimated following PP mesh implantation, which was not significantly different from the group of PVDF mesh samples (8.5±0.3). No control group had been analysed until now. Berndsen et al. compared a low-weight composite mesh (Vypro II) and a heavyweight mesh (Prolene) used for Lichtenstein repair in rats [17]. Ninety days after implantation, a median crosssectional area of the vas deferens was 109 pixels

27 Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure

for the Prolene and 158 pixels for the Vypro II side, with no significant difference. In our study, obstructions were analysed semiquantitatively using vasography. Investigations revealed obstructions that were mainly located at the mesh margins. The stiff PP mesh group showed an overall higher amount and degree of stenosis compared with the smooth PVDF mesh. Next to a significantly reduced inflammatory foreign body reaction of the PVDF (TUNEL 3.4±3.3%; Ki67 6.0±2.5%) compared with the PP mesh (TUNEL 12.7±8.0%; Ki67 7.4±1.8%), the lower number of obstructions was probably due to the elastic textile properties of the PVDF mesh. In contrast to the study by Shin et al., we could find no direct infiltration of the mesh fibres into the vas deferens. Obstructions were mainly due to compression of the wall at the mesh side, with an induced inflammatory and fibrotic reaction in the wall of the vas deferens. To summarize, great effort has been put into the challenge of creating a mesh material that optimises patients’ outcomes. The introduction of improved mesh materials has led to superior outcomes with regard to postoperative pain and foreign body sensation. However, the influence of different mesh materials on spermatic cord structures has not been studied thoroughly. For the first time, the construction of a large-pore and elastic monofilamentous PVDF mesh showed a beneficial effect on the integrity of the vas deferens in an experimental setting. However, no differences were observed in testicular function (temperature, volume, spermatogenesis).

References 1. Klosterhalfen B, Klinge U, Schumpelick V. Functional and morphological evaluation of different polypropylenemesh modifications for abdominal wall repair. Biomaterials 1998; 19(24):2235–2246 2. Junge K, Klinge U, Rosch R, Klosterhalfen B, Schumpelick V. Functional and morphologic properties of a modified mesh for inguinal hernia repair. World J Surg 2002; 26(12):1472–1480 3. Klinge U, Klosterhalfen B, Ottinger AP, Junge K, Schumpelick V. PVDF as a new polymer for the construction of surgical meshes. Biomaterials 2002; 23(16): 3487–3493

3

4. Junge K, Klinge U, Prescher A, Giboni P, Niewiera M, Schumpelick V. Elasticity of the anterior abdominal wall and impact for reparation of incisional hernias using mesh implants. Hernia 2001; 5(3):113–118 5. Klinge U, Klosterhalfen B, Conze J, Limberg W, Obolenski B, Ottinger AP et al. Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. Eur J Surg 1998; 164(12):951–960 6. Urban E, King MW, Guidoin R, Laroche G, Marois Y, Martin L et al. Why make monofilament sutures out of polyvinylidene fluoride? ASAIO J 1994; 40(2):145–156 7. Bringman S, Wollert S, Osterberg J, Smedberg S, Granlund H, Heikkinen TJ. Three-year results of a randomized clinical trial of lightweight or standard polypropylene mesh in Lichtenstein repair of primary inguinal hernia. Br J Surg 2006; 93(9):1056–1059 8. O’Dwyer PJ, Kingsnorth AN, Molloy RG, Small PK, Lammers B, Horeyseck G. Randomized clinical trial assessing impact of a lightweight or heavyweight mesh on chronic pain after inguinal hernia repair. Br J Surg 2005; 92(2):166–170 9. Horstmann R, Hellwig M, Classen C, Rottgermann S, Palmes D. Impact of polypropylene amount on functional outcome and quality of life after inguinal hernia repair by the TAPP procedure using pure, mixed, and titaniumcoated meshes. World J Surg 2006; 30(9):1742–1749 10. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewoud H, Bleichrodt R. Chronic pain after mesh repair of inguinal hernia: a systematic review. Am J Surg 2007; 194(3):394–400 11. Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1:2–25 12. Pollak R, Nyhus LM. Complications of groin hernia repair. Surg Clin North Am 1983; 63(6):1363–1371 13. Shin D, Lipshultz LI, Goldstein M, Barme GA, Fuchs EF, Nagler HM et al. Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction: a preventable cause of obstructive azoospermia. Ann Surg 2005; 241(4):553–558 14. Uzzo RG, Lemack GE, Morrissey KP, Goldstein M. The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 1999; 161(4):1344–1349 15. Goldenberg A, Matone J, Marcondes W, Herbella FA, Farah JF. Comparative study of inflammatory response and adhesions formation after fixation of different meshes for inguinal hernia repair in rabbits. Acta Cir Bras 2005; 20(5):347–352 16. Peiper C, Junge K, Klinge U, Strehlau E, Krones C, Ottinger A et al. The influence of inguinal mesh repair on the spermatic cord: a pilot study in the rabbit. J Invest Surg 2005; 18(5):273–278 17. Berndsen FH, Bjursten LM, Simanaitis M, Montgomery A. Does mesh implantation affect the spermatic cord structures after inguinal hernia surgery? An experimental study in rats. Eur Surg Res 2004; 36(5):318–322

28

Chapter 3 · Damage to the Spermatic Cord by the Lichtenstein Procedure in a Pig Model–Preliminary Results

Discussion Kehlet: If we see these very good pictures and

3

compare them to other studies concerning this problem, we should have an agreement using only one model to investigate this problem. Smeds: My question is, you have animals with damage and without damage in both groups with both types of meshes. Did you make a deeper analysis of this damage, and what is the reason for it? Junge: At this point we didn’t perform deeper analysis. We have to look on the histological sections to find out what is the detailed cause for this damage.

4

Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats C. Peiper, K. Junge, A. Oettinger, M. Binnebösel

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Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

Introduction

4

Modern concepts for treating inguinal hernias always include prosthetic mesh repairs. Some surgeons use the mesh repair exclusively [1]. Reported results are promising concerning recurrence rates [2] and return to physical activity [3]. On the other hand, there is a certain risk of complications due to the mesh that are difficult to detect. Alterations of fertility, if observable, may be recorded only in very large series. We know that prosthetic meshes implanted into the abdominal wall cause chronic inflammatory changes of the surrounding tissue [4]. Because of the close contact between mesh and the structures of the spermatic cord after inguinal mesh repair, these changes may also alter the reproductive structures in male patients. Case reports have been published about spermatic granuloma [5] and spermatoceles [6] after Lichtenstein hernia repair. Especially after mesh implantation in younger patients, these findings may be of great importance. In a rabbit experimental model, we investigated the interaction between mesh and the adjacent spermatic cord concerning the extent of inflammatory changes and their relationship to the material used, the integrity of the deferent duct, and the influence on the testicular function.

Materials and Methods These experiments were officially approved by the district president of North Rhine-Westphalia, Germany (AZ 50.203.2-AC 18, 3/01). All animals received humane care in accordance with the requirements of the German Animal Protection Act. All operations were carried out under general anesthesia. An intravenous catheter was placed into an ear vein. After premedication using subcutaneous buprenorphine 0.3 ml/kg, anesthesia was induced by injection of Domitor 0.3 ml/kg and ketamine 10% 0.2 ml/kg. Anesthesia was continued by repeated injections of these medications. Additionally, the animals were ventilated by isoflurane/air after endotracheal intubation. All animals received pulse oximetry and electrocardiographic monitoring during the operation. The animals were fixed in the supine position. After the fur was

cleaned and shaved, the skin was disinfected using Braunoderm, and the operating field was covered by sterile cloths. All operations were carried out under aseptic and sterile surgical conditions.

Rabbit Study 1 Eight chinchilla rabbits underwent unilateral inguinal hernia repair following the Lichtenstein approach [7]. All rabbits received implantation of a Marlex mesh (Bard, Cranston, RI, USA). This is a small-pore, heavyweight polypropylene mesh. Shouldice repair was carried out on the contralateral side [8]. Another three rabbits served as controls. Under aseptic conditions, the inguinal canal was opened by dividing the external oblique fascia, and the spermatic cord was secured by a loop. We preserved the cremasteric muscle. The Lichtenstein repair was performed with fixation of the mesh at the inguinal ligament and the internal oblique muscle using interrupted Miralene sutures (Miralene 0 HRT 26, Braun-Dexon). The lateral end of the mesh was slit into two tails and closed against the lateral aspect of the internal inguinal ring using Miralene sutures. Afterwards, the contralateral inguinal region was prepared. Here, a simple Shouldice repair was performed following the same extensive preparation using running Miralene sutures. Thus, every animal served as its own control. Animals were kept in standard rabbit cages of 60×60×60 cm at a temperature range of 20–22°C and a light circle of 12 h. They were fed dry pellets (Ssniff, 40 g/animal/day). Three months later, we evaluated testicular changes. The testicular volume was measured by ultrasound and calculated using the formula of a rotating ellipsoid [9]. Testicular temperature was evaluated using a digital thermometer (Voltcraft 300K) with a needle sensor. Arterial perfusion of the spermatic cord and testicles was investigated using the IC-VIEW system (Pulsion Medical Systems, Munich, Germany). Skin and subcutaneous tissue were removed from the lower abdomen, and the scrotal skin was removed completely (⊡ Fig. 4.1a). A 0.5 mg/kg bolus

31 Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

4

⊡ Table 4.1. Johnsen score for qualitative evaluation of spermatogenesis [10]

a

1

No cells in tubular section

2

No germ cells, but Sertoli cells present

3

Spermatogonia are the only germ cells present

4

Only a few spermatocytes (<5) and no spermatids or spermatozoa present

5

No spermatozoa and no spermatids, but several or many spermatocytes present

6

No spermatozoa and only a few spermatids (<5–10) present

7

No spermatozoa, but many spermatids present

8

Only a few spermatozoa (<5–10) present in section

9

Many spermatozoa present, but germinal epithelium disorganized, with marked sloughing or obliteration of lumen

10 b

c ⊡ Fig. 4.1. Testicles and spermatic cord of a rabbit after preparation and before evaluation of arterial perfusion (a), during flush of indocyanine green and under excitation of nearinfrared light (b), and after transfer of the fluorescence intensity into colors (c)

of indocyanine green (ICG) was injected intravenously into the ear vein. Excitation light was provided by an IC-VIEW system camera-mounted near a near-infrared (NIR) light source (780 nm). ICG-derived fluorescence was detected by a digital camera using the super-night-shot mode

Complete spermatogenesis with many spermatozoa (late spermatids)

(⊡ Fig. 4.1b) and was transferred to a computer for further quantification of perfusion-related fluorescence intensity (IC-CALC; ⊡ Fig. 4.1c). We calculated the difference between the intensity before and the maximum intensity after injection as an index for maximum perfusion. This parameter was recorded at the spermatic cord and at the testicles. Spermatogenesis as the main testicular function was estimated histologically using the Johnsen score [10] (⊡ Table. 4.1). The spermatic cords were excised, including the deep inguinal ring. Representative crosssections were obtained at this area and analyzed histologically using hematoxylin and eosin stains, focusing on the inflammatory response to the prosthetic mesh.

Rabbit Study 2 To differentiate among the results of different mesh materials, we conducted an additional animal study using the same conditions and techniques

32

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Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

mentioned above. We included 20 male chinchilla rabbits. All animals underwent bilateral Lichtenstein repair with a Prolene mesh (Ethicon, Norderstedt, Germany) on one side and Ultrapro mesh (Ethicon, Norderstedt, Germany) on the other side. Analysis followed after 6 months. After explantation of the inguinal region of the abdominal wall, we analyzed the patency of the vas deferens by injecting x-ray solution into the vas (⊡ Fig. 4.2). Additionally, we used light microscopy to measure the size of the foreign body granulomas induced by the meshes. Global statistical analysis was carried out using the Kruskal–Wallis test. For statistics among the groups, we used the Mann–Whitney test.

Injection of x-ray solution ligation of ductus

ductus mesh

testicle

⊡ Fig. 4.2. Vasography after resection of the inguinal region of the abdominal wall

⊡ Fig. 4.3. Testicular volume (ml) 3 months after groin mesh implantation in the rabbit

Results Rabbit Study 1 In the postoperative period, we observed an increased testicular volume (⊡ Fig. 4.3), with no difference between the kinds of repair (p=0.53), and a decreased testicular temperature compared with the controls (⊡ Fig. 4.4). Here, too, the differences among the operations were small (p=0.246). A cause for these findings may be the reduced arterial perfusion that exists after any repair (p<0.05). In comparison to the controls, this decrease in spermatic cord perfusion was more obvious after Lichtenstein repair (p=0.03; ⊡ Fig. 4.5) than after the Shouldice operation. The testicular perfusion was also significantly reduced after Lichtenstein mesh implantation (p<0.05; ⊡ Fig. 4.6). Evaluation of spermatogenesis revealed a decrease in the Johnsen 10 score in seminiferous tubules after Lichtenstein repair. Following Shouldice repair, the testicles showed regular spermatogenesis (p=0.20; ⊡ Fig. 4.7). During histological evaluation of the surrounding tissue, we observed a characteristic foreign body reaction to the mesh (⊡ Fig. 4.8), which we did not find after the Shouldice repairs. Destruction of the vas deferens wall or venous thrombosis was not detected. The duct was patent in all specimens. Obviously, the preserved cremasteric muscle protected the structures of the spermatic cord in this model.

33 Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

4

⊡ Fig. 4.4. Testicular temperature (°C) 3 months after groin mesh implantation in the rabbit

⊡ Fig. 4.5. Spermatic cord perfusion (a.u.) 3 months after groin mesh implantation in the rabbit, analyzed by the IC-VIEW system

⊡ Fig. 4.6. Testicular perfusion (a.u.) 3 months after groin mesh implantation in the rabbit, analyzed by the IC-VIEW system

⊡ Fig. 4.7. Percentage of mature spermatogenesis (Johnsen 10) 3 months after groin operation in the rabbit

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Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

Rabbit Study 2

4

⊡ Fig. 4.8. Inflammatory changes of the spermatic cord 3 months after Marlex mesh implantation in the rabbit (mesh fiber right upper, deferent duct left lower; hematoxylin and eosin, 100×)

During vasography, several specimens showed significant reduction of the vas deferens diameter (⊡ Fig. 4.9). Most of the obstructions were observed at the margin of the mesh. Severe obstruction (>75%) was found in 50% of the Prolene margins and 22.2% of the Ultrapro mesh edges. Within the mesh area, we saw no severe obstruction. Moderate obstruction (25–75%) also occurred more often in the Prolene group (⊡ Table. 4.2). Analysis of spermatogenesis revealed the same postoperative decrease in spermatozoa counted as Johnsen 10 after mesh implantation as was observed in the first study. Because of the different mesh material, the difference in the controls did not reach

⊡ Fig. 4.9. Vasography 6 months after inguinal Prolene mesh implantation in the rabbit

⊡ Table 4.2. Obstruction of the vas deferens 6 months after mesh implantation in the rat Obstruction at mesh margin

Obstruction within mesh area

0/+ (<25%)

++ (25–75%)

+++ (>75%)

0/+ (<25%)

++ (25–75%)

+++ (>75%)

Prolene

43.75% (7/16)

6.25% (1/16)

50% (8/16)

75% (12/16)

25% (4/16)

0% (0/16)

Ultrapro

77.8% (14/18)

0% (0/18)

22.2% (4/18)

83.3% (15/18)

16.7% (3/18)

0% (0/18)

35 Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

4

⊡ Fig. 4.10. Percentage of mature spermatogenesis (Johnsen 10) 6 months after groin mesh implantation in the rabbit

⊡ Fig. 4.11. Size of foreign body granuloma 6 months after groin mesh implantation in the rabbit

statistical difference. The decrease was also not different in the different material types (⊡ Fig. 4.10). Histological analysis revealed larger foreign body granulomas after Prolene mesh implantation than after Ultrapro mesh implantation (p<0.05, ⊡ Fig. 4.11).

Results in Rat Experiments Berndsen and colleagues conducted groin mesh implantation in 30 rats and analyzed the animals after 90 days. They found reduced s-testosterone

levels in the spermatic veins compared with the controls. Furthermore, the cross-sectional area of the vas deferens was also reduced after mesh implantation [11]. Taneli and colleagues published a study in 2005 that included 40 animals. Analysis was conducted 6 months after groin mesh implantation. An inducible nitric oxide synthase expression was detected in the ipsilateral testis after mesh implantation. Apoptotic cells were not detected. The authors concluded that long-term polypropylene mesh implantation has no effect on testicular hormonal function and only a limited effect on nitric oxide

36

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Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

levels and that this effect is not sufficient to cause testis apoptosis that could lead to infertility [12]. Kolbe and Lechner also investigated the effect of hernioplastic implants on male rat infertility, comparing the results after Prolene mesh implantation to the effects after Vypro II and with control animals. They observed some sperm granulomas in the Prolene group but saw no negative influence on male fertility in juvenile or adult rats [13]. The effect of the mesh on the vas deferens of the rat was investigated by Maciel and colleagues, with results published in 2007. They observed a foreign body reaction of the spermatic cord, including histological changes of the vas deferens, functional obstruction and dilatation of the duct, spermatozoid repression, and a loss of mucosal folding proximal to the mesh. In epididymides and testicles, no changes were found [14].

Discussion The effect on the surrounding soft tissue of longterm implantation of a mesh bioprosthesis for hernia repair is under current discussion and investigation. A persisting, inflammatory, proliferative foreign body reaction with increased cell turnover in the recipient tissues even years after implantation has been described [4]. These major inflammatory responses to mesh implantation have been mostly reported after incisional hernia repair, but also after bioprosthesis implantation in inguinal hernia operations. Therefore, we investigated the effect of this inflammatory reaction on the spermatic cord and testicular function in a rabbit model. We observed only minor inflammatory changes. Perhaps this reduced reaction was due to the short postoperative period. Despite this small morphological response, we found a significant influence on testicular perfusion and function. Testicular temperature was reduced in the postoperative phase after any repair, while testicular perfusion was lowest following the Lichtenstein operation. Spermatogenesis also showed a reaction to the implanted mesh. The amount of regular spermatogenesis classified as Johnsen 10 was reduced in comparison to that after Shouldice repair and in the controls, but this

difference did not reach statistical significance. No differences between the mesh materials were observed. Further experiments with larger groups seem to be necessary after this study. At first glance, the observed changes might be of no major clinical relevance in unilateral repair and could be important only in bilateral repairs. However, the literature contains several reports of serum antisperm antibody production after unilateral ischemic injury to the testis or the spermatic cord [15]. This has also been reported in patients after inguinal hernia repair [16, 17]. These antibodies may lead to male infertility even after unilateral changes and are therefore of major relevance. Further research on this topic is mandatory. The influence on humoral conditions will also be a topic of further investigations. Akbulut et al. observed decreased levels of testosterone after laparoscopic hernia repair (totally extraperitoneal repair) [18]. This finding is supported by animal experiments by Uzzo and colleagues in a canine model [19] and by Berndsen et al. in the rat [11]. One explanation for the morphological and functional changes observed in our study may be adhesion formation between the mesh and the structures of the spermatic cord as a result of the foreign body reaction. These adhesions were also described by Fitzgibbons et al. [20] in the pig. They found adhesions between the mesh and structures of the spermatic cord even after intraperitoneal placement of the mesh. LeBlanc et al. [21] placed a heavyweight polypropylene mesh into the preperitoneal space and also observed severe adhesions to the spermatic cord 30 days after implantation. Ninety days after operation, adhesions to the spermatic vessels and the spermatic cord as well as venous congestion of the testis were described. This may also serve as an explanation for the observed deferent duct obstruction in our experiments. One additional aspect is the protection of the structures of the spermatic cord by the cremasteric muscle. These structures were protected from inflammation if the cremasteric muscle was preserved, as we did in this rabbit model. Perhaps this strategy might be advisable instead of complete resection of the cremasteric muscle during mesh implantation.

37 Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

There are also reports about reactions to inguinal prosthetic mesh in men. The most important publication on this topic is by Shin and colleagues, published in 2005. They reported on 14 young male patients undergoing open or laparoscopic groin mesh implantation. Nine of them presented bilateral vas deferens obstruction, and the other five suffered from unilateral obstruction with contralateral testicular atrophy. The authors suggested that men–especially those of young reproductive age or with a solitary testicle–should be carefully advised of the potential for obstruction and compromise to future fertility before undergoing polypropylene mesh herniorrhaphy [22]. Valenti et al. reported a case of fibrotic vas deferens obstruction due to direct contact of an implanted plug with the vas [23]. Wingenbach et al. reported long-lasting pain during copulation in 3.9% of all cases after laparoscopic hernia repair [24]. Langenbach et al. found painful ejaculation in 10%, 12 weeks after laparoscopic repair [25], which correlated with the kind of mesh. Hetzer et al. reported spermatoceles requiring operation after Lichtenstein repairs in 0.8% [6]. Silich and McSherry reported a case of a spermatic granuloma requiring operation 2 years after mesh repair of an inguinal hernia [5]. Aasvang et al. conducted a questionnaire-based analysis of 1,015 patients 1 year after mesh-based inguinal hernia repair. They found relevant pain during physical activity in 18.4% and pain during sexual activity in 22.1%. Genital or ejaculatory pain occurred in 12.3%, and 2.8% of the patients complained about moderate or severe impairment of their sexual activity [26]. Out of this population, the authors intensified analysis in 10 selected patients with postherniotomy ejaculatory pain and pain-related sexual dysfunction. After this analysis, the authors concluded that postherniotomy genital and ejaculatory pain that impairs sexual activity is of neuropathic origin and is anatomically related to the vas deferens and related structures [27]. Summarizing these publications and our experimental results, we suggest some negative influence by the foreign body reaction to the prosthetic mesh on the structures of the spermatic cord. Therefore, we caution against implanting poly-

4

propylene mesh into the inguinal region without a good indication.

Conclusion Until more data are available, we see a limited indication for mesh implantation during inguinal hernia repair in young patients, as an effect on testicular function and spermatogenesis is possible. Preserving the cremasteric muscle fibers may protect the spermatic cord.

Acknowledgements Parts of these experiments were supported by the Deutsche Forschungsgemeinschaft (AZ KON 709/2002, PE 718/4-1).

References 1. Bittner R, Schmedt CG, Schwarz J, Kraft K, Leibl BJ. Laparoscopic transperitoneal procedure for routine repair of groin hernia. Br J Surg 2002; 89:1062–1066 2. Wara P, Bay-Nielsen M, Juul P, Bendix J, Kehlet H. Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of inguinal hernia. Br J Surg 2005; 92:1277–1281 3. Fenoglio ME, Bermas HR, Haun WE, Moore JT. Inguinal hernia repair: results using an open preperitoneal approach. Hernia 2005; 9:160–161 4. Klosterhalfen B, Klinge U, Hermanns B, Schumpelick V. Pathology of traditional surgical nets for hernia repair after long-term implantation in humans. Chirurg 2000; 71:43–51 5. Silich RC, McSherry CK. Spermatic granuloma. An uncommon complication of the tension-free repair. Surg Endosc 1996; 10:537–539 6. Hetzer FH, Hotz T, Steinke W, Schlumpf R, Decurtins M, Largiader F. Gold standard for inguinal hernia repair: Shouldice or Lichtenstein? Hernia 1999; 3:117–120 7. Lichtenstein IL, Shulman AG, Amid PK, Montllor MM. The tension-free hernioplasty. Am J Surg 1989; 157:188–193 8. Shouldice EE. Surgical treatment of hernia. Ontar Med Rev 1945; 4:43 9. Peiper Ch, Ponschek N, Truong S, Schumpelick V. Ultrasound-based volumetric evaluation of fluid retention after inguinal hernia repair. Surg Endosc 2000; 14:666–669 10. Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1970; 1:2–25

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Chapter 4 · Influence of Prosthetic Implants on Male Fertility in Rabbits and Rats

11. Berndsen FH, Bjursten LM, Simanaitis M, Montgomery A. Does mesh implantation affect the spermatic cord structures after inguinal hernia surgery? An experimental study in rats. Eur Surg Res 2004; 36:318–322 12. Taneli F, Aydede H, Vatansever S, Ulman C, Ari Z, Uyanik BS. The long-term effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis. Cell Biochem Funct 2005;23:213– 220 13. Kolbe T, Lechner W. Influence of hernioplastic implants on male fertility in rats. J Biomed Mater Res B Appl Biomater 2007; 81:435–440 14. Maciel LC, Glina S, Palma PC, Nascimento LF, Netto NR Jr. Histopathological alterations of the vas deferens in rats exposed to polypropylene mesh. BJU Int 2007; 100:187– 190 15. Lewis-Jones DI, Moreno de Marval M, Harrison RG. Impairment of rat spermatogenesis following unilateral experimental ischemia. Fertil Steril 1982; 38:482–490 16. Kapral W, Kollaritsch H, Stemberger H. Correlation of inguinal hernia and agglutinating sperm antibodies. Zentralbl Chir 1990; 115:369–377 17. Matsuda T, Muguruma K, Horii Y, Ogura K, Yoshida O. Serum antisperm antibodies in men with vas deferens obstruction caused by childhood inguinal herniorrhaphy. Fertil Steril 1993; 59:1095–1097 18. Akbulut G, Serteser M, Yucel A, Degirmenci B, Yilmaz S, Polat C, San O, Dilek ON. Can laparoscopic hernia repair alter function and volume of testis? Randomized clinical trial. Surg Laparosc Endosc Percutan Tech 2003; 13:377–381 19. Uzzo RG, Lemack GE, Morrissey KP, Goldstein M. The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 1999; 161:1344–1349 20. Fitzgibbons RJ Jr, Salerno GM, Filipi CJ, Hunter WJ, Watson P. A laparoscopic intraperitoneal onlay mesh technique for the repair of an indirect inguinal hernia. Ann Surg 1994; 219:144–156 21. LeBlanc KA, Booth WV, Whitaker JM, Baker D. In vivo study of meshes implanted over the inguinal ring and external iliac vessels in uncastrated pigs. Surg Endosc 1998; 12:247–251 22. Shin D, Lipshultz LI, Goldstein M, Barme GA, Fuchs EF, Nagler HM, McGallum SW, Niederberger CS, Schoor RA, Brugh VM 3rd, Honig SC. Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction: a preventable cause of obstructive azoospermia. Ann Surg 2005; 241:553–558 23. Valenti G, Baldassarre E, Torino G. Vas deferens obstruction due to fibrosis after plug hernioplasty. Am Surg 2006; 72:137–138 24. Wingenbach O, Waleczek H, Kozianka J. Laparoscopic hernioplasty by transabdominal preperitoneal approach. Analysis and review in 267 cases. Zentralbl Chir 2004; 129:369–373 25. Langenbach M, Schmidt J, Lazika M, Zirngibl H. Urological symptoms after laparoscopic hernia repair. Reduction

with a variant of polypropylene mesh. Urologe A 2003; 42:375–381 26. Aasvang EK, Møhl B, Bay-Nielsen M, Kehlet H. Pain-related sexual dysfunction after inguinal herniorrhaphy. Pain 2006; 122:258–263 27. Aasvang EK, Møhl B, Kehlet: Ejaculatory pain: a specific postherniotomy pain syndrome? Anesthesiology 2007; 107:298–304

5

The Effects of a Mesh Bioprosthesis on the Spermatic Cord Structures A. Goldenberg

40

Chapter 5 · The Effects of a Mesh Bioprosthesis on the Spermatic Cord Structures

Introduction

Experimental Study 2

We performed two experimental studies in a dog model [1, 2] and one clinical research study on the effects of synthetic mesh on fertility.

In the second investigation we studied the effects of polypropylene mesh implanted by inguinotomy in the spermatic cord, epididymis, and testis of dogs [2].

Experimental Study 1 Methods

5

The first work developed by our group concerned application of the mesh by video laparoscopy without dissection of the inguinal region. The aim of this study [1] was to investigate the effects of the synthetic mesh on the ductus deferens and testicle of dogs.

Methods Ten adult male dogs were anesthetized, and a 2.5×3.5 cm2 polypropylene mesh was fixed in the inguinal region in direct contact with the ductus deferens, using metallic staples without dissection of the region and, therefore, without manipulation. The right side, with no mesh, was the control. The operating time was 15 min. The animals were observed for 30 days, and then they were again anesthetized and underwent new surgery, during which the ductus deferens and testicle were removed and sent for histological analysis.

Results The histological sections of the testicle showed a focal reduction of spermatogenesis in 20% of the animals and a degenerative process in 20%. In the epididymis, chronic inflammation and seminiferous tubule dilatation were observed in 70%. A chronic inflammatory process was found in 60% of the vasa deferentia.

Conclusion The polypropylene mesh in direct contact with the spermatic funiculus in dogs caused histological alterations, with minimal reduction of spermatogenesis.

Eighteen dogs were included (12–23 kg), separated into three groups: -Group A (n=7): left side (with mesh) vs. right side (without mesh) -Group B (n=7): left side (without mesh) vs. right side (with mesh) -Group C (n=4): no surgical manipulation (control group) After being observed for 60 days, the animals were subjected to bilateral removal of the spermatic cord, epididymis, and testis, which were submitted for histological analysis. During the reoperation, a macroscopic evaluation was performed.

Results On the mesh side, we noted 100% mesh adherence to the posterior wall of the inguinal canal, as well as adherence of the spermatic cord to the mesh. Congestion of the pampiniform plexus was noted in three animals. Chronic inflammation and foreign body reactions in the spermatic cord were observed in 100% of the animals. On the side that was not implanted with mesh, a chronic inflammatory reaction was observed in 71% of the animals. All of the animals presented a chronic inflammatory reaction in the deferent duct on the mesh side, and such a reaction was also present in 11 animals in the side without the mesh. These alterations were not found in group C. There was a considerable statistical reduction in the average lumen diameter of the deferent duct on the mesh side. In the epididymis and testis, macroscopic and microscopic alterations were not significant, although one animal showed a marked reduction of spermatogenesis on the mesh side.

41 Chapter 5 · The Effects of a Mesh Bioprosthesis on the Spermatic Cord Structures

5

Conclusion

Acknowledgments

When in contact with the spermatic cord of dogs, the polypropylene mesh caused an intense chronic inflammatory reaction and a significant reduction in the diameter of the lumen of the deferent duct.

I am grateful for the collaboration in my research to Jaques Matone, Joaquim Ferreira de Paula, and Edgar Valente Lima Neto.

Clinical Study

1.

We performed one more study to evaluate testicular volume and arterial flow in patients undergoing surgical correction for inguinal hernia with a polypropylene prosthesis [3].

References

2.

3.

Methods This was an observational prospective clinical study of 39 male patients with unilateral inguinal hernia of Nyhus types IIIa and IIIb who underwent surgical correction with implantation of a polypropylene prosthesis by means of the Lichtenstein technique. The patients were evaluated using Doppler ultrasound before the operation and selectively 3 and 6 months after the operation. The variables studied were testicular volume, systolic and diastolic velocity, resistance index, and pulsatility index.

Results No statistically significant alterations in the studied variables were observed over the course of time: testicular volume (p=0.197), systolic velocity (p=0.257), diastolic velocity (p=0.554), resistance index (p=0.998), and pulsatility index (p=0.582).

Conclusion No alterations in testicular volume or arterial flow were observed over a 6-month period in patients who underwent surgical correction for inguinal hernia using a polypropylene prosthesis.

Goldenberg A, Matone J, Marcondes W, Focchi G. Effects of the polypropylene mesh in the testicle, epididymis and ductus deferens of dogs. Acta Cir Bras 2001; 16(4) Goldenberg A, Ferreira de Paula J. Effects of the polypropylene mesh implanted through inguinotomy in the spermatic funiculus, epididium and testis of dogs. Acta Cir Bras 2005; 20(6):461–467 Lima Neto EV, Goldenberg A, Jucá MJ. Prospective study on the effects of a polypropylene prosthesis on testicular volume and arterial flow in patients undergoing surgical correction for inguinal hernia. Acta Cir Bras 2007; 22(4): 266–271

Discussion Amid: Is there any direct contact between mesh

and the vas deferens during your laparoscopic approach? Goldenberg: No, there was no dissection and therefore no direct contact.

6

Influence of Prosthetic Implants on Male Fertility in Rats T. Kolbe and W. Lechner

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Chapter 6 · Influence of Prosthetic Implants on Male Fertility in Rats

Introduction

6

In an effort to find a suitable material for tensionfree repair of inguinal hernias, a variety of natural and synthetic materials have been used [1]. Currently, three prosthetic materials are widely used for repairing inguinal hernias: polyester, polypropylene, and expanded polytetrafluoroethylene [2]. Despite their wide acceptance and use in countless surgeries worldwide, little data exist regarding the effects of the mesh bioprosthesis on the adjacent spermatic cord structure and function, particularly the ductus deferens. Since it was shown that the weight of the implanted material corresponds to the postsurgical inflammatory reaction [3–5], partially absorbable meshes have been developed to reduce the amount of foreign material staying in the patient’s body. This study explored the vulnerability of the ductus deferens to mesh-induced inflammation and shrinkage after hernia repair in a rodent model. In our study we tested the influence on male fertility of a widely used mesh of 100% polypropylene (Prolene) and a mesh containing a mixture of 50% polypropylene and 50% polyglactin (Vypro II). The polyglactin component, which should be resorbed within 56–70 days, makes the mesh more flexible and reduces the implant’s weight. The bigger pores are regarded to be advantageous concerning the inflammatory reaction after implantation [6–8]. Due to the ethical constraints of studies in humans, we used rats as an animal model to test the vulnerability of the ductus deferens to the materials mentioned above. Because there are reports of special sensitivity of the premature male reproductive organs to surgical manipulations [9, 10], we tested both mature and premature male rats for short-term and long-term histological reactions and for subsequent reproductive performance.

Material and Methods Two types of implants (Prolene and Vypro II, both Ethicon, Germany) in the size of 2.25 cm2 were used in juvenile and adult Hsd:Sprague Dawley SD rats (8 weeks and 12 weeks, respectively). In two control groups (juvenile and adult male rats), the ducti were only bluntly separated from adherent

⊡ Fig. 6.1. Reproductive tract of male rat and implantation of meshes

tissue. Each of the six groups (Prolene juvenile, Pj; Prolene adult, Pa; Vypro II juvenile, Vj; Vypro II adult, Va; control juvenile, Cj; control adult, Ca) consisted of 10 animals. The meshes were surgically wrapped around the ductus deferens on each side to ensure direct contact with the spermatic cord and were fixed with sutures to remain in position (⊡ Fig. 6.1).

45 Chapter 6 · Influence of Prosthetic Implants on Male Fertility in Rats

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4 Weeks After Start: Histology The implants and the adjacent part of the ductus deferens from one side of each male rat were removed surgically for histological examination of acute inflammatory reaction. Staining was achieved with mouse antihuman proliferating cell nuclear antigen (PCNA) for detection of cell proliferation, rabbit antihuman factor VIII (Von Willebrand factor) for detection of angiogenic proliferation, and mouse antihuman bcl-2 (oncoprotein) for cancerogenic reaction. Counterstaining was done with Hemalaun.

a

3–4 Months After Start: Mating Test Three months after implantation, each male was mated with two or three adult females. Two days after positive vaginal plug control, the females were euthanized, and oocytes or embryos were flushed from the oviducts and uteri. The relationship of unfertilized and degenerated oocytes to morphologically intact embryos was recorded.

b

4 Months After Start: Histology The implant on the opposite side was removed after euthanasia for histological examination of chronic inflammatory reactions using the same methods as described above.

c

Results Histological Examination Hemalaun Staining Four weeks after treatment, two animals in the Pj group showed granulomatous inflammatory reactions with sperm deposits in the connective tissue due to injuries of the wall of the ductus deferens. Other rats in groups Pj and Pa showed incisions of the muscularis. There was enhanced production of collagen fibers at the edges of the Prolene im-

d ⊡ Fig. 6.2. a The two different implants. b Sperm granuloma. c Minor inflammation around a Prolene fiber (arrow). d Lumen of the ductus slightly depressed by Vypro II fibers (arrows)

46

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Chapter 6 · Influence of Prosthetic Implants on Male Fertility in Rats

plants. Areas of inflammation were visible around the Vypro II implants in groups Vj and Va, with many multinuclear giant cells (⊡ Fig. 6.2). There was no visible inflammatory reaction in the mucosa or blockage of the spermatic cord. In the samples taken after 4 months, we observed no profound differences from the first examination after 4 weeks. In the Prolene groups, there were incisions of the muscularis due to implant fibers, but no enhanced cellular reaction or inflammation-associated changes occurred. Two rats in the Pj group and three in the Pa group showed multinuclear giant cells. In the Vypro II groups, only the nonabsorbable component of the meshes was present. In some cases, the round lumen of the ductus deferens was slightly deformed, comparable to the Prolene groups, but without the incisions seen in the Pj and Pa groups.

PCNA Reaction Serosa Cells The staining for proliferative cells revealed increased inflammatory reactions after 4 months compared with the values after 4 weeks after treatment (⊡ Fig. 6.3a). While there was only a tendency in the Vypro and Prolene groups for more PCNApositive cells after 4 weeks, this difference was significant after 4 months (⊡ Fig. 6.3b). There was no significant difference between the mesh groups. We did not observe an age effect.

Mucosal Cells Between the mesh groups and controls, there was no significant difference in the percentage of PCNA-positive cells either after 4 weeks or after 4 months. Several groups showed high variation among individuals and thus a high standard of group values.

Von Willebrand Factor Staining Staining for Von Willebrand factor revealed an increase in the mean number of blood vessels in all groups between sampling points (⊡ Fig. 6.4). This proliferation ranged from 1.6% (Cj group) to 36% (Pj group). However, due to high individual variation, there was no statistically significant difference (as shown by analysis of variance) between the experimental groups.

⊡ Fig. 6.3. Proliferating cell nuclear antigen (PCNA)-positive cells in different cell layers 4 weeks and 4 months after implantation of meshes around the spermatic cord (mean and SE). a After 4 weeks. b After 4 months

Bcl-2 Staining There was no sign of oncogenic activity by expression of bcl-2 after either 4 weeks or after 4 months compared with positive controls.

6

47

No. of blood vessels per area counted

Chapter 6 · Influence of Prosthetic Implants on Male Fertility in Rats

25 20 15

after 4 weeks

10

after 4 months

5 0 Cj

Ca

Pj

Pa

Vj

Va

Experimental Groups ⊡ Fig. 6.4. Number of blood vessels per area counted at 4 weeks and 4 months (mean and range; minimum to maximum)

Mating Test The flushing of embryos resulted in mean embryo numbers from 7.7 to 14.7 in the experimental groups. These were compared to the total number of unfertilized or fragmented oocytes and embryos (range 13.0–16.3). All groups exhibited one to three males with decreased or restricted fertility, but there were no differences between groups. There was no indication of a negative influence on male fertility due to one of the implanted meshes (analysis of variance).

Discussion Open and laparoscopic mesh-based techniques dominate inguinal hernia repairs today. Research is currently focusing on the search for suitable mesh materials with regard to inflammatory response, chemical properties, and applicability [2]. The more rigid polypropylene mesh is preferred for laparoscopic hernia repair because it unfolds easily after introduction into the abdomen through the endoscope. A disadvantage is the heavy shrinkage of this material in vivo, which has been reported both in humans [4] and in animal experiments [5]. In contrast, other authors reported an even greater shrinkage of the more flexible Vypro II mesh (28%) compared with a heavyweight polypropylene mesh (Atrium, 12%) [11].

In our investigation, we used both materials in both juvenile and adult male rats. A direct mating test revealed no statistically significant differences between the two different materials or the different ages. Histological examination of spermatic cord explants stained with PCNA showed long-term inflammatory reactions in the adjacent serosa but not in the mucosa. This effect was independent of the material applied. This effect might be induced by the smaller pore size of the Prolene mesh, resulting in enhanced colonization with macrophages after 90 days [12, 13] and resorption of the polyglactin part in the Vypro II mesh. However, in both cases the mucosa was not involved. This result is in contrast to that found by Rosch et al. [14], but it confirms Berndsen et al. [15]. By measuring testicular hormonal function, the latter authors also confirmed that polypropylene and polypropylene/polyglactin meshes did not influence male fertility in the rat model, as had been concluded in another study [16]. The sharp edges and the unusual mode of application (wrapping around the spermatic cord) might be responsible for the observed sperm granulomas in two male rats and for the mesh incisions into the muscularis and granulosa in some rats of the Prolene group. From this point of view, the 50% absorbable Vypro II mesh with softer material properties seems to be more difficult to apply, but according to the results of other investigations [17], it causes less irritation to the surrounding tissue.

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Chapter 6 · Influence of Prosthetic Implants on Male Fertility in Rats

In summary, we did not observe a reduction in fertility of male rats compared with the controls, even after direct wrapping of synthetic meshes of two different types around the ducti deferentia. Therefore, we conclude that neither mesh has a negative influence on male fertility.

References

6

1. The EU Trialists Collaboration (2002) Repair of groin hernia with synthetic mesh: meta analysis of randomized controlled trials. Ann Surg 235:322–332 2. Nathan JD, Pappas TN (2003) Inguinal hernia: an old condition with new solutions. Ann Surg 238:148–157 3. Prior MJ, Williams EV, Shukla HS, Phillips S, Vig S, Lewis M (1998) Prospective randomized controlled trial comparing Lichtenstein with modified Bassini repair of inguinal hernia. J R Coll Surg Edinb 43:82–86 4. Schumpelick V, Arlt G, Schlachetzki A, Klosterhalfen B (1997) Chronic inguinal pain after transperitoneal mesh implantation. Case report of net shrinkage. Chirurg 68:1297–1300 5. Klinge U, Klosterhalfen B, Muller M, Ottinger AP, Schumpelick V (1998) Shrinking of polypropylene mesh in vivo: an experimental study in dogs. Eur J Surg 164:965–969 6. Klinge, U, Klosterhalfen B, Conze J, Limberg W, Obolenski B, Ottinger AP, Schumpelick V (1998) A modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. Eur J Surg 164:951 7. Klosterhalfen B, Junge K, Klinge U (2005) The lightweight and large porous mesh concept for hernia repair. Expert Rev Med Devices 2:103–117 8. Hagerty RD, Salzmann DL, Kleinert LB, Williams SK (2000) Cellular proliferation and macrophage populations associated with implanted expanded polytetrafluoro-ethylene and polyethyleneterephthalate. J Biomed Mater Res 49:489–497 9. Shandling B, Janik JS (1981) The vulnerability of the vas deferens. J Ped Surg 16:461–464 10. Barrat C, Seriser F, Arnoud R, Trouette P, Champault G (2004) Inguinal hernia repair with beta glucan-coated mesh: prospective multicenter study (115 cases)–preliminary results. Hernia 8:33–38 11. Scheidbach H, Tamme C, Tannapfel A, Lippert H, Kockerling F (2004) In vivo studies comparing the biocompatibility of various polypropylene meshes and their handling properties during endoscopic total extraperitoneal (TEP) patchplasty: an experimental study in pigs. Surg Endosc 18:211–220 12. Rosch R, Junge K, Schachtrupp A, Klinge U, Klosterhalfen B, Schumpelick V (2003) Mesh implants in hernia repair. Inflammatory cell response in a rat model. Eur Surg Res 35:161–166 13. Schumpelick V, Klinge U (2003) Prosthetic implants for hernia repair. Br J Surg 90:1457–1458

14. Rosch R, Junge K, Quester R, Klinge U, Klosterhalfen B, Schumpelick V (2003) Vypro II mesh in hernia repair: impact of polyglactin on long-term incorporation in rats. Eur Surg Res 35:445–450 15. Berndsen FH, Bjursten LM, Simanaitis M, Montgomery A (2004) Does mesh implantation affect the spermatic cord structures after inguinal hernia surgery? An experimental study in rats. Eur Surg Res 36:318–322 16. Taneli F, Aydede H, Vatansever S, Ulman C, Ari Z, Uyanik BS (2005) The long-term effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis. Cell Biochem Funct 23:213–220 17. Friis E, Lindahl F (1996) The tension-free hernioplasty in a randomized trial. Am J Surg 172:315–319

Discussion Schumpelick: I think this is the first study dealing

with fertility. Kolbe: Let me give at first one short comment on

this animal model. I believe that the rat model is a very good model to investigate tissue reaction. That seems to be comparable to the human situation. It seems not to be a good model for investigating testicular function because there are some differences from the human being. The rodent can retract the testicles into the body cave with different temperatures and conditions for spermatogenesis.

7

What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty? P. Witkowski

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Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty?

Introduction

7

The implantation of polypropylene mesh in inguinal hernia repair surgery has been a tremendous breakthrough. It has significantly reduced the hernia recurrence rate from 15–20% to 0.5–5% and therefore has decreased the rate of spermatic cord, vas deferens, and testicular artery injury due to reoperation for recurrence [1]. We have only limited information, however, about the long-term effects of polypropylene mesh implantation on the vas deferens, especially with regard to fertility. Despite new developments, polypropylene mesh remains the optimal and most commonly used material for inguinal hernioplasty. This mesh stimulates a pronounced chronic inflammatory reaction with connective tissue formation that incorporates the prosthesis into surrounding tissue. Although such scar formation fills out the hernia defect and effectively prevents hernia recurrence, it may ultimately cause damage to the adherent organs. This inflammatory process is clinically relevant because it remains active even years after mesh implantation [2].

Is There a Risk for a Vas Deferens Injury After Mesh Hernioplasty? In my opinion, we have enough clinical as well as experimental data from animal studies to confirm this risk. Injury may occur in the postoperative period because of a chronic foreign body reaction involving tissue surrounding the implanted mesh, which may also include the spermatic cord and vas deferens. Clinical experience indicates that a polypropylene mesh cannot be safely implanted in contact with any visceral or retroperitoneal organs, especially if placed under pressure or tension. Extensive fibrosis around the mesh can trap and damage inguinal nerves, the intestine, or the urinary bladder [3–5]. The mesh can even erode into the wall or lumen of those organs, leading to pain, infection, small bowel obstruction, or enterocutaneous fistula formation [3–7]. The same process may even lead to stenosis or obstruction of the urethra after polypropylene tape suspension for the treatment

of stress urinary incontinence [4]. Erosion of the vagina has also been reported [8, 9]. As a remedy, a new polypropylene sling with an absorbable central suburethral part was developed to separate the polypropylene part of the sling from the urethra and vagina [10]. All of the complications described above are recognizable on obvious clinical presentation and result from placement of the mesh in close proximity to the organs. Therefore, it is reasonable to expect that a structure as delicate as the vas deferens could also be damaged or occluded if a mesh were placed close enough to it, especially if left under tension or pressure. Animal studies provide more arguments for an increased risk of vas injury when polypropylene mesh is used for the repair. In several studies, mesh was found to be adherent to the spermatic cord throughout its inguinal course, leading to significant foreign body reaction in all animals [2, 11–13]. Histology showed fibrosis, extensive skeletal muscle degeneration, and histiocytic inflammation along the outer part of the cord [11, 14]. Additionally, the thick muscular layer of the vas was more prominently attenuated after mesh hernia repair than after Shouldice repair in a canine experiment [11]. This attenuation is important because the vas is no longer considered a passive conduit through which the ejaculate travels. The rich adrenergic innervation, the complexity of the muscle layers of the vas, and the metabolically active vasal epithelium all suggest a very active role in sperm transport, which may be altered by the perivasal fibrosis attributable to the mesh [11]. When a mesh was placed in proximity, the lumen of the vas was narrowed compared with nonsurgical controls [12]. Other studies also suggest that even if fibrosis around the vas deferens and within its wall does not lead to reduction of the lumen of the vas, it may cause functional obstruction with dilatation of the proximal segment along with degenerative changes in mucosa and repression of spermatozoa [11, 14]. Foreign body reaction around the mesh may compromise blood flow within the cord and eventually compromise fertility [15]. Congestion of the pampiniform plexus was noted in 20%

51 Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury

7

of animals after a Lichtenstein procedure, with spermatic cord vein thrombosis in up to 33% of cases after an open preperitoneal approach [2, 14]. Mesh repair led to decreases in arterial perfusion and testicular temperature and also reduced the proportion of seminiferous tubules with regular spermatogenesis [2]. Focal fibrinoid necrosis of the deferent duct wall was also reported [2]. The above results were observed in animals shortly after mesh implantation (weeks or months), whereas in humans, the mesh stays in the body for years and may cause much more extensive degenerative changes. Finally, several clinical reports conclude that occlusive injury to the vas deferens resulted from mesh implantation [7, 16–20]. Because these reports represent only single cases, until recently they had only anecdotal value. But a recent multicenter study has drawn attention to the possibility that vas deferens injury may take place more commonly than we think [21]. The authors presented 14 cases of obstructive azoospermia leading to infertility because of bilateral or unilateral vas occlusion, with simultaneous, but different, pathology of the reproductive organs on the contralateral side. Mesh-related fibrosis as a cause of vas occlusion was verified during surgical revision of the inguinal region [21]. Mechanical injury of the vas by the edge of the mesh has also been blamed as a possible cause of spermatic granuloma [20]. Further reports suggest that vas obstruction may lead to increased serum levels of antisperm antibody even without sperm granulomas, which can additionally compromise fertility [15, 22].

by that fact that most patients do not test their fertility before or after surgery, and occlusion can develop not only shortly after surgery but also years later, when a patient has finished his procreative activity. Furthermore, we do not have any noninvasive methods to detect vas injury or obstruction or to screen asymptomatic patients. Because we have animal experimental data indicating that fibrosis around the implanted mesh compromises vas deferens function, and knowing that the vas can be occluded when mesh is placed in proximity, as seen with urethral or small bowel obstruction, we cannot exclude the possibility that symptomatic patients from case reports are only the tip of the iceberg and that there are asymptomatic patients with vas deferens injury and occlusion after inguinal hernioplasty. The majority of patients may have this complication and may be completely unaware of it because they either do not test their fertility or they remain fertile because of an uncompromised contralateral sex organ.

How Great Is the Risk of Vas Injury After Mesh Hernioplasty?

Some surgeons may choose not to change anything and to continue using current surgical techniques until the actual risk rate is known. For the time being, I think that for patients whose procreative ability is of great concern, we should tailor our surgical approach to minimize the risk of vas injury without compromising repair results. These candidates would include young patients with bilateral hernia and those with compromised sex organs and contralateral hernia. Careful handling of the spermatic cord, including the vas deferens, in order to avoid direct

Today we cannot estimate the risk because we do not know how many patients are affected. This is mainly because of poor clinical presentation of the injury. Isolated, unilateral occlusion of the vas is completely asymptomatic. Infertility is the only potential symptom, and it occurs only with bilateral occlusion or with unilateral injury in a patient with contralateral sex organ pathology. Diagnosis of mesh-related vas injury is further complicated

How Can We Assess the Risk? Autopsies of patients who received inguinal mesh repair might give some estimates. Unfortunately, prospective studies with fertility monitoring before and after the procedure put a significant burden on patients and do not seem feasible at the moment [23].

What Can We Do Now?

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Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty?

intraoperative injury of this structure remains a constant principle of safe and efficient surgical technique [15]. To minimize the risk of vas occlusion, the general rule would be to avoid direct contact between the mesh and the vas deferens [24]: ▬ In the preperitoneal space the vas deferens is bare, so we may choose to avoid implanting mesh there, both in the posterior (laparoscopic, Nyhus, Stoppa, transabdominal preperitoneal, totally extraperitoneal repair) and anterior preperitoneal approaches (Rives, Kugel, Prolene Hernia System repair). ▬ Mesh plug insertion in the deep inguinal ring for indirect defects causes extensive fibrosis and may also involve the bare vas deferens; therefore, the plug is not advised in this location (Rutkow technique) [24]. ▬ In the course of the inguinal canal, the vas runs in the spermatic cord and is better protected by the surrounding internal spermatic fascia and cremaster. Therefore, it seems reasonable not to excise the cremaster but instead to spare it and close it with absorbable suture after hernia sac dissection and reduction. ▬ Placement of the mesh on the posterior wall of the inguinal canal is better (Lichtenstein or Trabucco technique) because the transversalis fascia can separate the mesh from bare vas running in the preperitoneal space. The disadvantage of the Lichtenstein operation, however, is that the spermatic cord is placed within the inguinal canal, where it is usually compressed between the mesh and the aponeurosis of the external oblique abdominal muscle. In such limited space, fibrosis around the mesh may still involve the spermatic cord and compromise the vas deferens. Therefore, we may modify our technique; after placing the mesh on the posterior wall of the inguinal canal, we can reapproximate the aponeurosis of the external oblique muscle with the sutures below (instead of above) the spermatic cord, as described in the Trabucco repair [25] (⊡ Figs. 7.1–7.3). This modification can be easy applied to the Lichtenstein operation, as has been previously suggested [26]. In this way, the spermatic cord is separated from the mesh with additional fascia and

⊡ Fig. 7.1. Placement of the mesh on the posterior of the inguinal canal

placed freely in subcutaneous tissue. Therefore, the risk of damage due to fibrosis surrounding the prosthesis is eliminated. Additionally, polypropylene mesh is placed flat between two fascial layers, the transversalis fascia and the oblique aponeurosis, which limits fibrotic tissue ingrowth only to the intrafascial space. Fibrosis penetrating the mesh glues the fascial layers together, creating a uniform, triple-layer (fascia– mesh–fascia) solid scar, which effectively reinforces the abdominal wall around the deep inguinal ring and prevents recurrence. After such repair, oblique passage of the spermatic cord through the inguinal canal can thus be avoided; it is not essential for effectiveness of the repair, as in traditional suture operations. This approach was developed by Trabucco in his sutureless technique, in which a preshaped polypropylene mesh with flat-shape memory is placed without suture fixation on the posterior wall of the inguinal canal [25]. Longterm results of this approach indicate that it is as effective as any other tension-free technique [27–30]. This technique is especially popular in Italy, with thousands of patients and years of experience. A randomized study could be organized to

53 Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury

⊡ Fig. 7.2. Closure of the aponeurosis of the external oblique muscle below (instead of above) the spermatic cord

⊡ Fig. 7.3. Closure of the lateral part of the aponeurosis of the external oblique muscle; the medial part of the aponeurosis is already closed below the spermatic cord

assess the effectiveness of such modification of the Lichtenstein technique, but in our opinion, a sufficient amount of indirect confirmatory evidence exists. Professor Smeds from Sweden started using this approach after our recent publication [26] a year ago and found only one (0.3%) recurrence after 300 repairs (personal communication). In my opinion, a shutter-valve effect of mesh tails sutured together and wrapping the cord is dangerous because it unnecessarily enhances contact between the surface of the mesh with the cord, creating a cuff that contracts substantially around the spermatic cord in the postoperative

7

period as the mesh contracts. It may compromise the vas as well as blood vessels within the cord. Moreover, the sharp edge of the mesh on which the spermatic cord directly kinks upon entering the inguinal canal from the deep inguinal ring is considered a common place for vas injury. A flat, preshaped onlay mesh with a hole for the spermatic cord decreases contact between the mesh and the cord without compromising the effectiveness of the Lichtenstein technique. The efficacy of this approach was clearly proven by the Trabucco technique and other repairs using a preshaped onlay mesh with a preformed hole for the spermatic cord. In the above proposed approach, direct kinking of the cord over the mesh is avoided, and the cord instead folds over the fascia of the external aponeurosis while entering the subcutaneous space. The proposed surgical techniques comply with the principles of the tension-free operation and can be easily implemented. In summary, although the actual rate of vas deferens injury due to fibroblastic inflammation around polypropylene mesh is not yet known, there is strong experimental and clinical evidence that such processes can and do take place. Therefore, until the risk is fully investigated, all patients with any known compromise to their reproductive health or with concerns about fertility can be offered a surgical technique that minimizes the potential risk without diminishing all the advantages of tension-free hernia repair. Isolating the spermatic cord from the mesh by placing it above (not below) the aponeurosis of the oblique abdominal muscle seems to be an easy, applicable, and effective solution.

References 1. Fitzgibbons RJ Jr. (2005) Can we be sure polypropylene mesh causes infertility? Ann Surg 241:55–561 2. Peiper Ch, Klinge U, Junge K, Schumpelick V (2006) Is there a risk of infertility after inguinal mesh repair? Experimental study in pig and the rabbit. Hernia 10:7–12 3. Amid PK (2004) Radiologic images of meshoma: a new phenomenon causing chronic pain after prosthetic repair of abdominal wall hernias. Arch Surg 139:1297–1298 4. Chuback JA, Singh RS, Sills C, et al. (2000) Small bowel obstruction resulting from mesh plug migration after open inguinal hernia repair. Surgery 127:475–476

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Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury due to Inguinal Hernioplasty?

5. Agrawal A, Avill R (2005) Mesh migration following repair if inguinal hernia: a case report and review of literature. Hernia 10:79–82 6. Jeans S, Williams GL, Stephenson BM (2007) Migration after open mesh plug inguinal hernioplasty: a review of the literature. Am Surg 73:207–209 7. Weber-Sánchez A, García-Barrionuevo A, Vázquez-Frias JA, Cueto-Garcia J (1999) Laparoscopic management of spermatic cord entrapment after laparoscopic inguinal herniorrhaphy. Surg Laparosc Endosc Percutan Tech 9:296-9 8. Sweat SD, Itano NB, Clemens JQ, et al. (2002) Polypropylene mesh tape for stress urinary incontinence: complications of urethral erosion and outlet obstruction. J Urol 168:144–146 9. Dunn JS Jr, Bent AE, Ellerkman RM et al. (2004) Voiding dysfunction after surgery for stress incontinence: literature review and survey results. Int Urogynecol J Pelvic Floor Dysfunct 15:25–31 10. Trabucco AF, Blitstein J (2004) T-sling for the treatment of stress urinary incontinence. Am J Urol Rev 12:583–588 11. Uzzo RG, Lemack GE, Morrissey KP, Goldstein M (1999) The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 161(4):1344–1349 12. Goldenberg A, Paula JF (2005) Effects of the polypropylene mesh implanted through inguinotomy in the spermatic funiculus, epididium and testis of dogs. Acta Cir Bras 20(6):461–467 13. Berndsen FH, Bjursten LM, Simanaitis M, Montgomery A (2004) Does mesh implantation affect the spermatic cord structures after inguinal hernia surgery? An experimental study in rats. Eur Surg Res 36(5):318–322 14. Maciel LC, Glina S, Palma PC, Nascimento LF, Netto NR Jr. (2007) Histopathological alterations of the vas deferens in rats exposed to polypropylene mesh. BJU Int 100:187–190. Erratum in: Costa Nascimento FC [corrected to Nascimento, Luiz FC] (2007) BJU Int 100:481 15. Ridgway PF, Shah J, Darzi AW (2002) Male genital tract injuries after contemporary inguinal hernia repair. BJU Int 90:272–276 16. Valenti G, Baldassarre E, Torino G (2006) Vas deferens obstruction due to fibrosis after plug hernioplasty. Am Surg 72:137–138 17. Nagler HM, Belletete BA, Gerber E, Dinlenc CZ (2005) Laparoscopic retrieval of retroperitoneal vas deferens in vasovasostomy for postinguinal herniorrhaphy obstructive azoospermia. Fertil Steril 83:1842 18. Meacham RB (2002) From androlog. Potential for vasal occlusion among men after hernia repair using mesh. J Androl 23:759-761 19. Aasvang EK, Kehlet H (2008) Postherniotomy dysejaculation: successful treatment with mesh removal and nerve transection. Hernia 12:645–647 20. Silich RC, McSherry CK (1996) Spermatic granuloma. An uncommon complication of the tension-free hernia repair. Surg Endosc 10:537–539

21. Shin D, Lipshultz LI, Goldstein M, Barmé GA, Fuchs EF, Nagler HM, McCallum SW, Niederberger CS, Schoor RA, Brugh VM 3rd, Honig SC (2005) Herniorrhaphy with polypropylene mesh causing inguinal vassal obstruction: a preventable cause of obstructive azoospermia. Ann Surg 241:553–558 22. Matsuda T, Muguruma K, Horii Y, Ogura K, Yoshida O (1993) Serum antisperm antibodies in men with vas deferens obstruction caused by childhood inguinal herniorrhaphy. Fertil Steril 59:1095–1097 23. Agarwal BB, Sinha BK, Mahajan KC (2008) The risk of communicating TEP-related infertility risk is an opportunity and not a »Cinderella concern« anymore. Surg Endosc 22:1557–1558 24. Valenti G, Baldassarre E (2006) Vasal obstruction after hernioplasty: the importance of surgical strategy in preventing azoospermia. Ann Surg 244:160; author reply 160 25. Trabucco EE, Trabucco AF (2002) Tension-free, sutureless, preshaped mesh hernioplasty. In: Nyhus LM, Condon RE (eds) Hernia, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 159–164 26. Witkowski P, Trabucco EE (2007) Is there an increased risk of the vas deferens occlusion after meshes inguinal hernioplasty and what can we do about it? Ann Surg. 245:153–154 27. Trabucco EE, Trabucco AF (1998) Flat plug and mesh hernioplasty in the »inguinal box«: description of the surgical technique. Hernia 2:133–138 28. Adamonis W, Witkowski P, Smietanski M, et al. (2006) Is there a need for a mesh plug in inguinal hernia repair? Randomized, prospective study of the use of Herta 1 mesh compared to PerFix Plug. Hernia 10:223–228 29. Cucci M, De Carlo A, Di Luzio P, et al. (2002) The Trabucco technique in the treatment of inguinal hernias: a six-year experience. Minerva Chir 57:457– 459 30. Testini M, Miniello S, Piccinni G, et al. (2002) Trabucco versus Rutkow versus Lichtenstein techniques in the treatment of groin hernia: a controlled randomized clinical trial. Minerva Chir 57:371–376

Discussion Deysine: The previous study did not show much damage caused by the mesh. The differences were not statistically significant in most cases. So we don’t have any hard data to prove anything at this time. I would suggest that until we have more hard data, human hard data, we should restrain the kind of language that we use when we express our impressions. Köckerling: I have to speak for the endoscopic procedure. At the moment, we really have no data,

55 Chapter 7 · What Can We Do To Decrease the Risk of Vas Deferens Injury

even no clinical data, showing that there is really a higher problem for vas deferens injury or any other influence on that system due to endoscopic inguinal hernia repair. So I wouldn’t go so far as to exclude this technique in younger patients who are fertile. Maybe we will have some problems. We should carefully look at those problems, learn how to avoid them, and choose the right mesh, but we shouldn’t go so far as to exclude all mesh procedures. Kehlet: I think we are at the state where we can say that we should not dissect the cremaster from the cord. Amid: We have to understand that if we use a mesh and we don’t remove the cremastic muscle, none of these potential problems will occur.

7

8

The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair H. Aydede

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Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair

Introduction

8

Polypropylene mesh currently finds widespread use throughout the world in hernia repair, as it is well tolerated by the body and allows tissue ingrowth into the prosthesis [1]. Experimentally, all meshes cause an initial inflammatory tissue response in the recipient after implantation [2]. Interestingly, in most clinical studies in humans, these meshes are described as inert materials, but systematic morphological examinations of the long-term effects of meshes commonly used for hernia repair in humans are rare [3]. Nitric oxide (NO), a freely diffusible, water- and lipid-soluble molecule, is formed from L-arginine and molecular oxygen by a family of nitric oxide synthases [4]. In the testis, nitric oxide synthase (NOS) from endothelial cells (eNOS) is expressed in the Leydig cell, Sertoli cell, spermatocyte, and spermatid [5]. Expression of inducible NO synthase (iNOS) requires transcriptional activation, which is induced by various combinations of cytokines [6]. The upregulation of NOS leads to excessive NO production for prolonged periods of time and accounts for oxyradical-mediated damage [6]. Although little is known about the mechanism of its toxicity in germ cell injury from testicular ischemia, NO is an important mediator of cell death through either apoptosis or necrosis, depending on the intensity and duration of injury [7]. The aim of the present study was to investigate long-term effects of mesh implantation on testicular hormone function and NO metabolism [8]. Testicular hormone function was evaluated by assessments of serum luteinizing hormone (LH) and folliclestimulating hormone (FSH) levels. Testicular NO metabolism was investigated by testicular NO levels, iNOS, and eNOS expressions. Testicular ischemic damage impairing spermatogenesis with the possibility of leading to male infertility was assessed by germ-cell-specific apoptosis in the rat testis.

Material and Methods Animals and Surgical Technique The study comprised 40 male Swiss albino rats, 10–12 weeks old and 200–220 g in weight. The rats

were housed in a temperature- and light-controlled environment with ad libitum access to water and rat food pellets for 3 days before the study. All experimental procedures were approved by the Experimental Animal Research Ethics Committee of the Faculty of Medicine. All surgical procedures were performed under general anesthesia administered by intramuscular injection of ketamine and xylazine hydrochloride, employing sterile techniques.

Experimental Design The animals were randomly allocated into two groups, each containing 20 rats. In group 1, the operation was performed using an infrainguinal incision above the scrotum, and the inguinal anatomy was explored. The left spermatic cord was elevated, and a 0.5×1.0-cm polypropylene mesh (Surgipro, United States Surgical, Norwalk, CT, USA) was placed behind the left inguinal spermatic cord. To avoid displacement, the mesh was sutured to aponeurotic tissue behind the spermatic cord using 4/0 polypropylene. In group 2, the sham-operated controls, the left inguinal spermatic cord was elevated and left in place with no further manipulations. An intracardiac blood sample (1 ml) was obtained for biochemical analysis from both groups during the preoperative period. All animals were housed in standard conditions in the experimental research laboratory for 6 months. After 6 months, before the rats were sacrificed, a 2-ml sample of intracardiac blood was taken, and both testes were removed for examination. All testes were divided into two halves. One half of each testicular sample was placed in Bouin’s fixative solution for histological evaluation, and the other halves were snap-frozen in liquid nitrogen and stored at -70ºC for biochemical evaluation.

Assessment of Hormonal Function of the Testes Serum samples were frozen at -70ºC for batch analysis. Serum LH and FSH levels were assessed by immunoradiometric assay methods with DPC (Diagnostic Products, Los Angeles, CA, USA) re-

59 Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis

agents. The method sensitivities were 0.15 mIU/ ml-1 and 0.06 mIU/ml-1. Intra-assay precisions were 1.6 and 7.1%, and interassay precisions were 3.8% and 5.7% for LH and FSH, respectively.

Concentration of NO in Testes In estimating the tissue NO production, biochemical assessments of stable NO oxidative metabolite (nitrite and nitrate) levels were analyzed. Assessments of tissue nitrite and nitrate levels were based on the Griess method. The absorbance of the reaction mixture was measured at 545 nm with a spectrophotometer (Shimadzu, Japan). A standard curve was obtained with concentrations of 2–10 mmol/l-1 sodium nitrate. Data in this study present the total nitrite and nitrate, which are NO metabolites and are expressed as mmol/g-1 wet tissue.

8

a terminal deoxynucleotidyl transferase-mediated biotin nick end–labeling (TUNEL) method. Fragmentation of DNA in the nucleus is one of the first morphological changes in the apoptotic process and can be detected in histological sections using the TUNEL method performed with a commercial kit, such as the DeadEnd Colorimetric TUNEL system (Promega G7130), according to the manufacturer’s instructions. The quantification of apoptosis was carried out in a blind fashion by two independent observers.

Statistical Evaluation Statistical analyses were performed with SPSS 10.0 software. Groups were compared using a twotailed Student’s t-test, one-way ANOVA test, and Mann–Whitney U-test. Values of p<0.05 were considered to indicate statistical significance.

Immunohistochemical Evaluation Results All specimens were fixed in Bouin’s solution for 24 h. Sections (5 mm thick) from paraffin blocks were incubated in a solution of 3% H2O2 for 15 min to inhibit endogenous peroxidase activity. Then sections were washed with phosphate base solution (PBS) and incubated for 18 h at 4ºC with primary antibodies: anti-iNOS at a 1/100 dilution (Zymed 61-7700) and anti-eNOS at a 1/200 dilution (Biomol SA-258). Afterwards, sections were washed three times for 5 min each with PBS, followed by incubation with biotinylated IgG and then with streptavidin–peroxidase conjugate (Dako). They were incubated with DAB (3.3’-diaminobenzidine) substrate for detection of immunoreactivity. Control samples were processed in an identical manner, but the primary antibody step was omitted. Staining intensity was graded as mild (+), moderate (++), or strong (+++).

Detection of Apoptotic Cell Death In Situ Using the TUNEL Method To obtain evidence for induction of programmed cell death, apoptotic cells were identified using

Testicular tissue NO levels in ipsilateral and contralateral testes in the mesh-implanted group and sham-operated control groups are shown in ⊡ Table 8.1. We found significant increases in the ipsilateral testicular NO level compared with the contralateral NO level in the mesh-implanted group and the control group (p=0.0001, p=0.002, respectively). Comparison of the mesh-implanted group and the control group revealed significantly (p=0.015) higher NO levels in the ipsilateral mesh group. The results of hormonal evaluation of testicular function of the study groups preoperatively and 6 months postoperatively are given as mean ± standard deviation. Serum LH and FSH levels are summarized in ⊡ Table 8.2 for preoperative serum samples and 6-month postoperative serum samples in the mesh-implanted group and the sham-operated control group. No significant statistical differences between preoperative and postoperative samples were seen in serum LH or FSH levels. We found mild (+) eNOS activity in ipsilateral and contralateral specimens of the mesh-implanted and sham-operated groups. However, (+)

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Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair

⊡ Table 8.1. Testicular tissue nitric oxide (NO) levels in ipsilateral and contralateral testes in the mesh and sham-operated control groups (values given as mean ± standard deviation) NO (μmol-1 wet tissue)

Ipsilateral testis a

Mesh group

230.3±90.9

Sham-operated control group

166.56±32.0a

Contralateral testis

P

180.6±74.8

0.0001

140.88±29.3

0.002

a

P=0.015

⊡ Table 8.2. Serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the preoperative and postoperative periods in the mesh-implanted and sham-operated control groups (values given as mean ± standard deviation) Mesh-implanted group

-1)

LH (mIU/ml

8

-1)

FSH (mIU/ml

Sham-operated control group

Preoperative

Postoperative

Preoperative

Postoperative

0.582±0.065

0.571±0.084

0.626±0.086

0.636±0.088

0.362±0.050

0.353±0.041

0.385±0.043

0.340±0.050

iNOS activity was observed only in the ipsilateral testis of the mesh-implanted study group, and no expression was detected in the remaining samples (⊡ Fig. 8.1). TUNEL (+) apoptotic germ cells were not detected in any of the samples.

Discussion The major finding of the present study was that no apoptotic TUNEL (+) cells were present in the mesh-implanted study group. Therefore, we believe that mesh implantation does not cause secondary ischemic changes in testicular function over the long term. It has been shown that acute graded reductions in testicular blood flow affect the early stages of spermatogenesis, which may have a major impact on sperm production [9]. In my study in 2003, we evaluated the longterm effect of mesh and its localization (i.e., anterior or posterior) on testicular perfusion and function in groin hernia patients. Testicular function was evaluated with spermiograms and testicular perfusion with color Doppler ultrasonography. Group I consisted of 30 posterior preperitoneal mesh repair patients, and group II consisted of an-

terior tension-free repair patients. There were no statistically significant differences between the preoperative and postoperative spermiogram results for either group. No statistically significant difference was found between the two groups in terms of Doppler flow parameters (peak systolic velocity, end diastolic velocity, resistive index, pulsatility index) for preoperative, early, or late postoperative periods. When Doppler flow parameters were compared for group I, a statistically significant difference was found between preoperative and early postoperative values. No statistically significant difference was found between preoperative and late postoperative values. This was also true for early postoperative values versus late postoperative values. When Doppler flow parameters were compared for group II, a statistically significant difference was found between preoperative and early postoperative values. No statistically significant difference was found between preoperative and late postoperative values. This was also true for early postoperative values versus late postoperative values. No statistically significant difference was observed between preoperative and late postoperative Doppler flow parameters, nor was a statistically significant difference seen between the preoperative and day-75 postoperative spermio-

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61 Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis

Ipsilateral

Mesh

Control

Contralateral

Mesh

Control

⊡ Fig. 8.1. Mild positive (+) iNOS immunostaining is shown in the stroma of the ipsilateral testis (a) of the mesh-implanted study group. Negative (-) iNOS immunostaining is shown in

the contralateral (b) testis of the mesh-implanted study group and ipsilateral (c) and contralateral (d) testes of the shamoperated control group. ×400 original magnifications

gram results for either mesh repair group. Bearing in mind the experimentally proven chronic inflammatory tissue reaction against mesh, these results indicate that chronic tissue inflammation has no adverse effect on testicular perfusion or spermatogenetic function over time [10]. The production of NO as well as its injurious metabolite peroxynitrite and other reactive nitrogen species may result in a cascade of events leading to DNA fragmentation and apoptosis. It is well known that the early stages of spermatogenesis are very sensitive to a moderate, acute reduction in blood flow, and consistent reductions in blood flow may interfere with sperm production and adversely affect fertility [11]. NO is one of many inflammatory mediators, which include the adhesion molecules and cytokines that contribute to the inflammatory cell adherence of testicular microvascular endothelium and lead to microcirculatory failure. Apoptosis is directly linked to the recruitment of neutrophils to subtunical venules [11]. NO is important in increasing blood flow and inhibiting leukocyte accumulation [12]. In addi-

tion, NO has a dual effect. On the one hand, it is vasodilatory in modest increases and potentially protective of testicular tissue, but on the other hand, excessive amounts can exert cytotoxic effects in combination with other cytokines and may result in testicular germ-cell-specific apoptosis. In the present study, we observed a significant increase in NO level and mild (+) iNOS expression in the ipsilateral side of the mesh-implanted group, which suggests ischemic/inflammatory injury of the mesh-implanted testis; however, this injury was not sufficient to cause germ cell apoptosis in the testicular tissue. In a study investigating the eNOS immunostaining and apoptosis in testicular ischemia, it was reported that acute (3 h) testicular ischemia resulted in germ cell apoptosis, and strong eNOS immunostaining was detected in the cytoplasm of degenerating germ cells [13]. The authors suggest that strong eNOS immunostaining is associated with germ cell apoptosis. Similarly, in our observations in the present study, the long-term results of mesh implantation revealed mild (+) eNOS

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Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis Used for Inguinal Hernia Repair

expressions in all samples, and no apoptotic germ cells were observed in testicular tissue. In the present study we found no statistical difference in serum hormone levels between the mesh-implanted study groups and the sham-operated controls. Thus, long-term mesh implantation does not cause biochemical alteration of the hormonal functions of the testes. Part of this study was presented at the 13th European Microscopy Congress in 2004. Our presented results demonstrated that cells with pyknotic nuclei, which indicate apoptotic cells, were observed less in the mesh group than in the control group when analyzed both by light and electron microscopy [14]. In conclusion, using prosthetic mesh in humans did not cause any defects in testicular perfusion or spermatogenetic function. In this experimental model, NO level as an oxidative damage indicator was found to be increased in rat testes, and iNOS overexpression was detected immunohistochemically. The increased level of NO is one of the apoptotic promoters. However, finding no difference for apoptosis and no ultrastructural difference in electron microscopy emphasizes that this oxidative damage is compensated for by testicular tissue. Thus, prosthetic mesh repair in patients undergoing infertility treatment can be meticulously reevaluated.

7. Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA (1995) Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with Nmethy-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 92:7162–7166 8. Taneli F, Aydede H, Vatansever S, Ulman C, Arı Z, Uyanık BS (2005) The long-term effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis. Cell Biochem Funct 23:213–220 9. Berg A, Collin O, Lissbrant E (2001) Effect of acute graded reduction in testicular blood flow on testicular morphology in the adult rat. Biol Reprod 64:13–20 10. Aydede H, Erhan Y, Sakarya A, Kara E, Iklgül O, Can M (2003) Effect of mesh and its localisation on testicular flow and spermatogenesis in patients with groin hernia. Acta Chir Belg 103:607–610 11. Lysiak JJ, Turner SD, Nguyen QAT, Singbarth K, Ley K, Turner TT (2001) Essential role of neutrophils in germ cell-specific apoptosis following ischemia/reperfusion of mouse testis. Biol Reprod 65:718–725 12. Lissbrant E, Lofmark U, Collin O, Berg A (1997) Is nitric oxide involved in the regulation of rat testicular vasculature? Biol Reprod 56:1221–1227 13. Zini A, Abitbol J, Girardi SK, Schulsinger D, Goldstein M, Schegel PN (1998) Germ cell apoptosis and endothelial nitric oxide synthase (eNOS) expression following ischemiareperfusion injury to testis. Arch Androl 41:57–65 14. Vatansever HS, Taneli F, Kayma F, Köse CF, Müftüoğlu S, İlgül O (2004) Testicular nitric oxide levels and apoptosis in rat testes during inguinal hernia repair after using long-term mesh bioprosthesis. In: Proceedings of the13th European Microscopy Congress, Antwerp, Belgium, 22–27 August 2004

References

Discussion

1. DeBorg JR (1998) The historical development of prosthetics in hernia surgery. Surg Clin North Am 78:973–1006 2. Klinge U, Klosterhalfen B, Müller M, Schumpelick V (1999) Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 165:665–673 3. Bendavid R (1998) Complications of groin hernia surgery. Surg Clin North Am 78:1080–1103 4. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142 5. Zini A, O’Bryan MK, Magid MS, Schlegel PN (1996) Immunohistochemical localisation of endothelial nitric oxide synthase in human testis, epididymis and vas deferens suggest a possible role for nitric oxide in spermatogenesis, sperm maturation and programmed cell death. Biol Reprod 55:935–941 6. Nathan C (1997) Inducible nitric oxide synthase: what differences does it make? J Clin Invest 100:2417–2423

Schumpelick: I looked for your spermiograms.

Did you see any differences in motility or in any other analysis of testicular function besides the spermiograms according to the investigation period? Aydede: You are right. In our study we found no statistical significant difference between the different investigation time points. Klinge: The point I want to address is the method of statistical analysis. You frequently said that some differences were statistically significant or not significant. I’m not sure whether many of these data were really normal distributed. If you compare just the means between two groups, I’m not sure if some single details, such as a complete constric-

63 Chapter 8 · The Long-Term Effect on Testicular Function of a Mesh Bioprosthesis

tion of the vas, will be detected by this test. Did you use some other statistical tests for subgroups in your entire cohort? Aydede: At this time I can’t give you more information about statistical analysis than the Mann– Whitney U-test. We should do a more detailed analysis. Gryska: In the very first clinical study, how many patients did you have in each group? Aydede: We had about 30 patients in each group.

8

9

Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like? U. Muschaweck

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Chapter 9 · Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like?

Introduction Lichtenstein repair is recommended in national guidelines as the first choice for uncomplicated primary inguinal hernia. It is known as easy to perform, has a short learning curve, and is said to have the smallest risk for recurrent hernia and other complications. However, in the year 2007 we had to reoperate on 232 patients with recurrent hernia, making up 20% of all our operations. Of these, 31 had had a previous Lichtenstein repair. In all 31 cases, the intraoperative findings showed complete incorporation of at least one nerve, mesh shrinkage and migration, and excessive scar tissue in the area of the external oblique fascia, the internal oblique muscle, and the groin ligament. We always had to remove the mesh completely because of the tissue damage in the groin canal. Also, neurectomy of at least one nerve always had to be done.

⊡ Fig. 9.1. Case 1: hardened mesh with stiff, sharp edges; vas adherent to mesh edge

9 Case Reports We have selected six cases of patients with severe chronic groin pain resulting in reoperation with impressive intraoperative findings. Two of these had a severed vas that was caused by the mesh.

Case 1: DL, 62-Year-Old Man from Wales

⊡ Fig. 9.2. Case 1: ilioinguinal nerve thickened; surface rough, not shiny; surrounded by fibrotic tissue. Recurrent hernia 3×3 cm

History: Lichtenstein repair in Cardiff, Wales, in October 2006. After 1 year, massive pain in the groin and radiating, burning pain to the scrotal area and penis. Unable to walk more than 30 m. Applied surgical technique: Removal of the mesh, neurectomy of the ilioinguinal nerve, Lichtenstein repair with UltraPro mesh (⊡ Figs. 9.1 and 9.2). Patient immediately free of pain. Electron microscopy and histological findings: Heavyweight small-pore polypropylene mesh; ingrowth of nerve with marked perineural fibrosis; posttraumatic neuroma (⊡ Fig. 9.3).

⊡ Fig. 9.3. Case 1: heavyweight small-pore polypropylene mesh; ingrowth of nerve with marked perineural fibrosis; posttraumatic neuroma

67 Chapter 9 · Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like?

Case 2: HB, 61-Year-Old Man from Germany

9

Electron microscopy and histological findings: Large-pore polypropylene mesh (⊡ Fig. 9.6), moderate foreign body reaction (epithelioid cell type).

History: Lichtenstein repair in Oldenburg, Germany, in October 2006. After 8 months, new bulge was present, with pressure and pain in the groin and severe pain during ejaculation.

Case 3: MR, 26-Year-Old Man from Denmark

Intraoperative findings: Excessive scar tissue; mesh surrounding vas at the internal ring (⊡ Figs. 9.4 and 9.5).

History: Lichtenstein repair in September 2007, with pain starting immediately afterward. Reoperation in December 2007.

Applied surgical technique: Removal of the mesh, neurectomy of the ilioinguinal nerve, minimal repair (suture repair). Patient immediately free of pain.

Intraoperative findings: Mesh covering the ilioinguinal nerve completely; nerve partly growing into the mesh (⊡ Fig. 9.7).

⊡ Fig. 9.4. Case 2: excessive scar tissue; mesh surrounds vas at the internal ring

⊡ Fig. 9.6. Case 2: large-pore polypropylene mesh, moderate foreign body reaction (epithelioid cell type)

⊡ Fig. 9.5. Case 2: ilioinguinal nerve thickened and grown into the upper edge of the mesh, surrounded by fibrotic tissue; lateral recurrent hernia 8×2 cm

⊡ Fig. 9.7. Case 3: mesh covers the ilioinguinal nerve completely; nerve partly growing into the mesh; small medial recurrent hernia

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Chapter 9 · Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like?

⊡ Fig. 9.8. Case 3: heavyweight small-pore polypropylene mesh, foreign body granuloma, perineural fibrosis

9

⊡ Fig. 9.9. Case 4: inguinal nerve ingrowth into mesh; lateral edge of mesh rolled up and penetrating through the fascia and subcutaneous tissue; palpable through skin. No recurrent hernia

Applied surgical technique: Removal of the mesh with neurectomy and minimal repair. Electron microscopy and histological findings: Heavyweight small-pore polypropylene mesh (⊡ Fig. 9.8), foreign body granuloma, perineural fibrosis. Low-grade infection with neutrophilic granulocytes.

Case 4: GM, 40-Year-Old Man from Italy History: Lichtenstein repair in 2005, with pain starting immediately afterward. Reoperation in February 2008. Intraoperative findings: Inguinal nerve ingrowth into mesh; lateral edge of mesh rolled up and penetrating through the fascia and subcutaneous tissue; palpable through the skin (⊡ Fig. 9.9). No recurrent hernia.

⊡ Fig. 9.10. Case 4: double-layered, heavyweight, small-pore polypropylene mesh

Case 5: JC, 66-Year-Old Man from England

Applied surgical technique: Removal of the mesh with only a neurectomy done.

History: Lichtenstein repair in 2001, reoperation in 2008.

Electron microscopy and histological findings: Double-layered, heavyweight, small-pore polypropylene mesh, bulky board of scar, beginnings of calcification (⊡ Fig. 9.10).

Intraoperative findings: Mesh corrugated, only partial ingrowth (⊡ Fig. 9.11). Ilioinguinal nerve adherent to mesh over 2 cm. Lateral recurrent hernia 3×2 cm.

69 Chapter 9 · Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like?

⊡ Fig. 9.11. Case 5: mesh corrugated; only partial ingrowth. Ilioinguinal nerve adherent to mesh over 2 cm. Lateral recurrent hernia 3×2 cm

9

⊡ Fig. 9.12. Case 5: mesh type uncertain, chronic inflammation (giant cells)

Applied surgical technique: Removal of the mesh, neurectomy, Lichtenstein repair with UltraPro mesh. Electron microscopy and histological findings: Mesh type uncertain (⊡ Fig. 9.12), chronic inflammation (giant cells).

Case 6: HW, 29-Year-Old Woman from Germany History: Lichtenstein repair in March 2006. Pain started in August 2007; reoperation in February 2008.

⊡ Fig. 9.13. Case 6: Vypro mesh with ingrowth of ilioinguinal nerve. Medial recurrent hernia 3×2.5 cm

Intraoperative findings: Small amount of Vypro mesh with ingrowth of ilioinguinal nerve (⊡ Fig. 9.13). Medial recurrent hernia 3×2.5 cm. Applied surgical technique: Removal of the mesh (⊡ Fig. 9.14), followed by neurectomy and minimal repair. Electron microscopy and histological findings: Vypro mesh with posttraumatic neuroma and marked perineural fibrosis. ⊡ Fig. 9.14. Case 6: removal of the mesh, followed by neurectomy and minimal repair

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Chapter 9 · Reoperation Following Lichtenstein Repair: What Do Vas and Nerves Look Like?

Is the Mesh Type Important? This sample of six patients whom we looked at in greater detail is certainly very small. But there is only a slight tendency that heavyweight mesh might be more often involved (see ⊡ Table 9.1).

Summary In these six patients, heavyweight small-pore meshes were slightly more predominant than heavyweight large-pore or lightweight meshes. But more important than the choice of mesh is the surgical handling of the nerve. (Is a primary resection better than keeping the nerve?) Therefore, the indication for mesh repair must be carefully considered, particularly in young patients.

9

⊡ Table 9.1. Mesh types encountered in the six cases and examined by electron microscopy Polypropylene

4

Heavyweight small-pore

3

Heavyweight large-pore

1

Vypro

1

Unknown (could not be analyzed)

1

Discussion Schumpelick: You mentioned that the nerve has

grown into the mesh, but it may be that the mesh has grown into the nerve. Muschawek: You are right; during the explantation you are not able to see which direction was the right one. Miserez: Two questions on the six patients you operated on for pain and recurrence. First, is it enough to do a single neurectomy, and second, do we need to remove the mesh for pain? Muschawek: I’m sure, because the mesh always covers the nerve, and if you lift up the mesh you can see the nerve going into the mesh. And in

most cases there is only one nerve left. So I prefer resecting the mesh and the mesh in this case. Uzzo: In the literature you find up to a 10% chronic pain rate after Lichtenstein repair. I think we should stop saying that Lichtenstein repair is easy to perform. You said it during your slides. Obviously, it’s not easy. Muschawek: You are right. It looks easy, but there are many details you have to think about. Heniford: I think we should put all these problem patients together with a standard study protocol, and we will get very quickly large numbers of patients through which we can answer questions. Klinge: You have a lot of experience with recurrent hernias. Do you think that it makes a difference in reoperating after 2 years or after 10 years? Muschawek: No. You will have the adhesion within a few weeks after operation. Kehlet: I just remember the first reports about pain after Lichtenstein repair. Now we are sitting here for a full meeting discussing chronic pain. So I think we have to be careful also with this fertility problem. We have to look at it, and we cannot say it is probably not a real problem.

10

Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review R. C. Read

72

Chapter 10 · Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review

Introduction

10

Complications following repair of inguinal herniation have historically been attributed to poor surgical technique and blamed on inexperience. Those related to the spermatic cord, testicular atrophy and occlusion of the vas deferens, are dreaded because the patient, angry that his manhood has been threatened, often resorts to litigation. Ischemia of the testicle was said to be the result of a too-tight reconstruction of the internal inguinal ring [1]. Injury to the vas deferens is presumed to arise after harsh separation of the hernial sac. The former may be ligated, divided, or devascularized. Considered rare, it is underreported because most men undergoing groin repair tend to be older and are no longer concerned about their reproductive capacity. Because most inguinal herniae are unilateral, younger men rarely face sterility. Nevertheless, a significant minority have bilateral repairs. Further, cryptorchidism or later epididymitis can eliminate the spermatic contribution from the contralateral groin.

Sutured Repair During the latter half of the 20th century, the Shouldice–Bassini procedure became the gold standard for groin hernioplasty. In the early 1980s, Wantz and Bendavid, two pioneers in herniology, separately focused attention on testicular ischemia and vasal narrowing. In 1982, Wantz [2, 3] reported that 11 of 1,682 patients developed orchitis within a week. All had had complete removal of their scrotal sacs. After the same operation was performed on 311 men for recurrence, seven progressed to testicular atrophy. Wantz blamed dissection through scarred tissue. The common feature was thrombosis affecting the pampiniform plexus and leading to venous infarction. Wantz pointed out that constriction at the internal inguinal ring was not responsible because ligation of testicular veins at this level, which is standard treatment for varicocele, does not cause testicular infarction. To avoid this complication, he recommended that in a complete indirect inguinal hernia, dissection of the hernial sac should not proceed beyond the level

of the pubic tubercle. Division of the peritoneal sac there allows for reduction and inversion of its proximal portion into the preperitoneal space. In cases of recurrent herniation, a posterior preperitoneal approach to repair should be employed, thereby avoiding dissection of a scarred spermatic cord. Adopting these ideas for his next group of 4,000 Shouldice hernioplasties resulted in only one case of ischemic orchitis. In 1983, Bendavid encountered a patient who complained of episodes of brief, severe pain in the groin during ejaculation. He had previously been operated on using the Shouldice procedure. By 1991, another 16 cases had been identified, two of whom had not received surgery but suffered from chronic epididymitis or cancer of the prostate treated with radiotherapy. The next year, Bendavid labeled this new syndrome »dysejaculation« [4]. Another 13 cases were reported in 1995 [5]. Symptomatology began 1 month to 2 years postoperatively. Reoperation showed either separation of the vas deferens from its blood supply, adherence to the transversalis fascial floor of the inguinal canal, kinking, abrasions, stricture, or scarring. Bendavid considered that the mechanism for pain was retrograde distension of a blocked vas deferens, since ejaculation begins with peristalsis in the epididymis, passing down to the seminal vesicles and prostate. Delay in onset postoperatively indicated scarring secondary to the dissection that had been required to remove both the cremasteric musculature and the hernial sac. Because some of Bendavid’s patients became pain free over time, conservative treatment was recommended.

Prosthetic Repair [6] Reinforcement of sutured hernioplasties began in the last decade of the 19th century, a few years after Bassini’s cure became well known. In 1894, Phelps employed silver coils. Later, filigrees of other metals were used. However, rigidity, fibrosis, sinuses, radiopacity, and both patient and surgeon discomfort discouraged their use. In 1944, Aquaviva and Bounet introduced Nylon mesh. Their prosthetic design remains, but polypropylene, which was first used by Usher in 1963, is now the most popular

73 Chapter 10 · Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review

mesh. Nevertheless, it was not until the final decade of the 20th century that a majority of groin repairs became prosthetic and the Lichtenstein procedure was the new gold standard. This change resulted from a significant reduction in the rate of recurrent herniation. LeBlanc et al. [7], using endoscopy, placed mesh preperitoneally overlying the internal inguinal ring of pigs. Examples of venous congestion in the pampiniform plexus were found, indicating that the posterior preperitoneal approach to the groin does not preclude venous infarction of the testicle. In 1999, Uzzo et al. [8] claimed to be the first to examine the effects of mesh-induced fibrosis on components of the spermatic cord. Using dogs, unilateral inguinal defects were created and repaired using either polypropylene mesh or the Shouldice technique. The contralateral groin served as a control. A year later, autopsies revealed patent but significantly narrowed vasa deferentia in both repair groups. Hydroceles and testicular atrophy were found in half of the dogs treated with mesh; none followed sutured repair. Taylor et al. [9] studied patients who had undergone repair of unilateral inguinal herniation with either the laparoscopic or anterior prosthetic (polypropylene) technique 3 years previously. There was no significant effect on testicular blood flow. Zieren et al. [10] reported in 2001 that testicular perfusion remained unchanged 6 months after patients received plug-and-patch repairs for inguinal herniation. Aydede et al. [11] obtained similar results, long term, after randomly assigning patients to anterior or preperitoneal prosthetic repair. Laparoscopic mesh repair of inguinal herniae was found to result in dysejaculation that began an average of 3 months postoperatively in 10% [12] or 3.9% [13] of patients. Thus, as with damage to the pampiniform plexus, the preperitoneal approach does not confer exemption from injury to the vas deferens. Its incidence appears to increase with the use of mesh. Silich and McSherry [14] reported a patient with a sperm granuloma 4 years after a Lichtenstein repair. They believe it arose from erosion of the vas deferens by the cut edge of the mesh at the medial end of the slit made to recreate the internal inguinal ring. Berndsen et al. [15] compared the effects of heavy or lightweight

10

polypropylene mesh on the spermatic cords of rats 3 months after Lichtenstein repair, using the Shouldice procedure as control. Interestingly, they found impaired testosterone production and narrowing of the vas deferens only with low-weight composite mesh. There was no difference in the inflammation or fibrosis evoked by the different meshes, contrary to results from previous studies [16, 17]. Dilek et al. [18] measured testicular blood flow before and 3 months after patients were randomly assigned to laparoscopic or Lichtenstein repair of inguinal herniation. Neither technique affected testicular blood flow. Taneli et al. [19] studied testicular metabolism in rats whose spermatic cord was exposed to a layer of polypropylene mesh. Findings were compared to those for sham-operated controls 6 months later. There was no significant difference in serum hormone levels or apoptosis in the testes. Their results support the 2001 results of Zieren et al. [10] and Taylor et al. [9]. Shin et al. [20] presented their multi-institutional experience of 14 younger men previously repaired for inguinal herniae, mainly using the Lichtenstein procedure, who reported infertility. Nine had bilateral vasal obstruction, and five had unilateral obstruction with contralateral testicular atrophy or epididymitis. The mechanism was dense fibrosis. All had normal blood hormone levels. The authors point out that the vasal narrowing described by Uzzo et al. [8] at 1 year postoperatively could, over time, become an occlusion. Iatrogenic injury to the vas deferens such as ligation, cauterization, incision, or vascular compromise could also be a factor. Goldenberg and de Paula [21] studied the 2-month effect of simulated polypropylene mesh repair in the groin of dogs. Observations were compared with contralateral dissected or unoperated controls. The inflammatory response–100% with mesh, 71% without–involved the vas deferens in all subjects in the mesh group, causing statistically significant narrowing. A third of the animals that received mesh showed congestion of the pampiniform plexus. Peiper et al. [22] experimented on pigs and rabbits to determine whether a risk of infertility exists after inguinal mesh repair. In the former, transinguinal preperitoneal repair with polypropylene mesh, after resection of the cre-

74

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Chapter 10 · Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review

master, was compared to a contralateral Shouldice procedure. Within a month, one-third of those receiving mesh demonstrated venous thrombosis in the pampiniform plexus even though the spermatic cord was exposed to the prosthesis only at the internal inguinal ring. The rabbits underwent unilateral Lichtenstein repair with preservation of the cremaster muscle, and contralateral Shouldice repair was also undertaken. Testicular parameters were compared with those of unoperated controls. Each repair reduced perfusion, more so with Lichtenstein. Kolbe and Lechner [23] wrapped the vasa deferentia of rats with either heavyweight or lightweight polypropylene mesh. After 3 months, their fertility was determined by mating them and counting the oocytes or embryos. Some sperm granulomas were observed in the heavyweight mesh group, but neither prosthesis reduced fertility compared with controls, which had simply undergone isolation of the vas deferens. Interestingly, both meshes induced a similar inflammatory reaction, supporting the work of Berndsen et al. [15] but not that of others [16, 17]. Witkowski and Trabucco [24] questioned the reported increased risk of vas deferens occlusion after mesh inguinal hernioplasty. They cite Fitzgibbons [25], who has argued that »no correlation between fibrosis and vasal obstruction has been proven.« Witkowski and Trabucco [24] stated, as did Shin et al. [20], that it is therefore possible that intraoperative damage from dissection or fixation is responsible. Regardless, they suggest separating the mesh from the spermatic cord by placing it subcutaneously à la Halsted–Bassini. In 2008 Gventatadze [26] tested the effect of such isolation on sperm morphology in patients undergoing the modified bilateral Lichtenstein repair. Comparison was made with others receiving the classic procedure. A statistically significant deterioration (p<0.01) in sperm parameters was found in the latter.

Conclusions In summary, venous infarction of the testicle (atrophy) and narrowing of the vas deferens (dysejaculation) were rarely reported following su-

tured repair (Shouldice). The risk to the spermatic cord increases after its isolation by excision of the cremaster muscle and scrotal sacs. Reoperation requiring dissection through scar tissue jeopardizes the cord, and tissue reaction to prostheses augments damage to cord structures. Lightweight mesh cannot be relied upon to evoke less fibrosis than heavyweight mesh. Spermatic cord complications are not avoided by preperitoneal placement of prostheses. Pathology, secondary to groin dissection and the use of mesh, has been shown to affect the vas deferens more often than the pampiniform plexus. Arterial flow to the testis is affected little by prosthetic repair unless, in a minority, venous thrombosis supervenes. Vasal occlusion is underreported since most inguinal herniorrhapies are performed on the elderly, who usually are not concerned about fertility. In younger men, sterility is generally not a problem because most repairs are unilateral. However, contralateral diseases or bilateral hernioplasties can result in sterility. It has been reported that subcutaneous placement of the spermatic cord in men after bilateral Lichtenstein repair, as recommended by Witkowski and Trabucco, significantly improves fertility compared with the classic Lichtenstein procedure.

References 1. Koontz AR (1965) Atrophy of the testicle as a surgical risk. Surg Gynecol Obstet 120:511–513 2. Wantz GE (1982) Testicular atrophy as a risk of inguinal hernioplasty. Surg Gynecol Obstet 154:570–571 3. Fong Y, Wantz GE (1992) Prevention of ischemic orchitis during inguinal hernioplasty. Surg Gynecol Obstet 174:399–402 4. Bendavid R (1992) »Dysejaculation«: an unusual complication of inguinal herniorrhaphy. Postgrad Gen Surg 4(2):139–141 5. Bendavid R (1995) Dysejaculation. Probl Gen Surg 12(2):237–238 6. Read RC (2004) Milestones in the history of hernia surgery: prosthetic repair. Hernia 8:8–14 7. LeBlanc KA, Booth WV, Whitaker JM et al. (1998) In vivo study of meshes implanted over the inguinal ring and external iliac vessels in uncastrated pigs. Surg Endosc 12:247–251 8. Uzzo RG, Lemack GE, Morrissey KP et al. (1999) The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 161(4):1344– 1349

75 Chapter 10 · Damage to the Spermatic Cord from Groin Herniorrhaphy: A Review

9. Taylor SG, Hair A, Baxter GM et al. (2001) Does contraction of mesh following tension-free hernioplasty affect testicular or femoral vessel blood flow? Hernia 5:13–15 10. Zieren J, Beyersdorff D, Beier KM et al. (2001) Sexual function and testicular perfusion after inguinal hernia repair with mesh. Am J Surg 181:204–206 11. Aydede H, Erhan Y, Sakarya A et al. (2003) Effect of mesh and its localization on testicular flow and spermatogenesis in patients with groin hernia. Acta Chir Belge 103 (6):607–610 12. Langenbach M, Schmidt J, Lazika M et al. (2003) Urological symptoms after laparoscopic hernia repair. Reduction with a variant of polypropylene mesh. Urologe 42:375–381 13. Wingenbach O, Waleczek H, Kozianka J (2004) Laparoscopic hernioplasty by transabdominal preperitoneal approach. Analysis and review in 267 cases. Zentralbl Chir 129:369–373 14. Silich RC, McSherry CK (2006) Spermatic granuloma. An uncommon complication of the tension-free hernia repair. Surg Endosc 10(5):537–539 15. Berndsen FH, Bjursten LM, Simanaitis M et al. (2004) Does mesh implantation affect the spermatic cord structures after inguinal hernia surgery? An experimental study in rats. Eur Surg Res 36:318–322. 16. Klosterhalfen B, Klinge U, Schumpelick V (1998) Functional and morphological evaluation of different polypropylene mesh modifications for abdominal wall repair. Biomaterials 19:2235–2246 17. Junge K, Klinge U, Rosch R et al. (2002) Functional and morphological properties of a modified mesh for inguinal hernia repair. World J Surg 26:1472–1480 18. Dilek ON, Yucel A, Akbulut G et al. (2005) Are there adverse effects of herniorrhaphy techniques on testicular perfusion? Evaluation by color Doppler ultrasonography. Urol Int 75:167–169 19. Taneli F, Aydede H, Vatansever S et al. (2005) The longterm effect of mesh bioprosthesis in inguinal hernia repair on testicular nitric oxide metabolism and apoptosis in rat testis. Cell Biochem Funct 23:213–220 20. Shin D, Lipshultz LI, Goldstein M et al. (2005) Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction. A preventable cause of obstructive azoospermia. Ann Surg 241(4):553–558 21. Goldenberg A, de Paula JF (2005) Effects of polypropylene mesh implanted through inguinotomy on the spermatic funiculus, epididymis and testis of dogs. Acta Cir Bras 20(6):461–467 22. Peiper C, Junge K, Klinge U et al. (2006) Is there a risk of infertility after inguinal mesh repair? Experimental studies in the pig and rabbit. Hernia 10(1):7–12 23. Kolbe T, Lechner W (2007) Influence of hernioplastic implants on male fertility in rats. J Biomed Mater Res B Appl Biomater 81B:435–440 24. Witkowski P, Trabucco EE (2007) Is there an increased risk of vas deferens occlusion after mesh inguinal hernioplasty and what we can do about it? [letter] Ann Surg 245(1):153–154

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25. Fitzgibbons RJ Jr (2005) Can we be sure polypropylene mesh causes infertility? Ann Surg 241:559–561 26. Gvenetadze T (2008) Method of spermatic cord isolation from the mesh. In: Proceedings of the American Hernia Society annual meeting, Scottsdale, Arizona, 12–16 March 2008, poster 23

II

II

Risk for Infection

11

Mesh Infection Following Hernia Repair: A Frequent Problem? – 79

12

Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery – 87

13

Mesh-Related Infections After Hernia Repair – 97

14

Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field – 103

15

Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh – 113

16

Mesh Infection–Therapeutic Options – 119

17

Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery? – 125

18

Infection Control in a Hernia Clinic: 24-Year Results of Aseptic and Antiseptic Measure Implementation in 4,620 »Clean Cases« Based on Up-To-Date Microbiological Research – 135

19

Components Separation Technique: Pros and Cons – 143

11

Mesh Infection Following Hernia Repair: A Frequent Problem? B. J. Lammers, A. Baer, T. Sauer, P. Pohl, P. E. Goretzki

80

Chapter 11 · Mesh Infection Following Hernia Repair: A Frequent Problem?

Introduction

11

Wound and mesh infections after hernia repair are very severe complications. On the one hand, today it is well established to repair hernias with meshes in very different ways, but on the other hand, knowledge of the incidence of severe infections, including mesh infection, is quite rare [1, 2]. In this chapter we aim to define which kinds of infections we can recognise. The rate of infection after mesh repair differs, of course, between inguinal hernia repair and incisional hernia repair. In the United States it is very common to use the group of ventral hernias of the abdominal wall (including incisional, epigastric, Spigelian, and umbilical hernias). According to the infection, we will look at infections in this group as well as in inguinal hernias, including femoral hernias. Therefore, we will address just two groups: ventral hernias (laparoscopic and open) and inguinal hernias (open and laparoscopic procedures). Using new techniques and new materials, it is impossible to define detailed risk factors for wound and mesh infection that are related to each procedure and each material. The literature includes some references on this; these will be remarked upon in this chapter regarding some special topics. Further investigations are necessary, and the authors of other chapters will also comment on this topic.

Definition of Surgical Site Infection Using the definition of the Centers for Disease Control and Prevention, infections are divided into superficial and deep infections. Superficial infection occurs in the first 30 days after an intervention, and deep infection occurs within 1 year and involves the fascia, the muscle layers, and the graft. We must recognise that there are early infections within the first 30 days after implantation and late infections that may occur years after implantation. Furthermore, we may encounter further intraabdominal problems, such as abscess formation, bowel injury, peritonitis, and so on, with both early and late onset.

Looking through the literature, no definitions of mesh infection are available. But at the very least, there is a risk of infection of the mesh with any kind of wound infection, so we should be alert for signs of deep infection, including the mesh (onlay, intraperitoneal onlay, sublay, etc.): ▬ Fever ▬ Signs of infection (swelling, oedema) ▬ C-reactive protein and leucocytosis ▬ Contaminated mesh Inguinal hernia surgery is primarily sterile surgery with low contamination. In abdominal wall surgery, the infection rate is higher, so it must be regarded as contaminated surgery.

Materials and Methods We did a literature review of papers involving more than 100 patients with ventral hernia repair and incisional hernia repair, and we also included our own data. The main topic of this investigation was the rate of infections, including mesh-related infections, if these data were available. However, many papers lacked information on this problem. The group of inguinal hernia repairs was covered by an overview of inguinal hernia repair in the North Rhine region of Germany for a period of 10 years with almost 200,000 operations [3]. This period included the development of a reporting system and the new video-assisted technologies (transabdominal preperitoneal and totally extraperitoneal repair). There are very few papers on mesh infection in inguinal hernia repair. Fistula formation is also very rare, so this was not discussed in this overview. Obviously, the problem in inguinal hernia repair nowadays is not evident.

Results Ventral Hernias and Incisional Hernia Repairs Without Mesh Repair This operation, which is done in many countries using direct suture or doubling of the fascia (called the Mayo repair in Germany), is not standard

81 Chapter 11 · Mesh Infection Following Hernia Repair: A Frequent Problem?

therapy today because mesh repair is accepted. However, many patients need a nonmesh repair. The infection rate with antibiotic prophylaxis is about 6–10 % [4–6]. Our own experiences with a long-term run of 20 years show an infection rate of 12%, including complete wound rupture. These data show the general problem of incisional hernia repair: contaminated surgery. The rate of postoperative infections is over 10%. The bacteria stay in the wound for a long time.

Incisional Hernias with Mesh Repair We analysed the publications involving more than 100 patients. Many of them are multicentre studies; there is just one randomised multicenter study, from Conze [7]. Leber et al. showed in a retrospective study in 1998 that in open mesh repair, many early and late postoperative problems occur. Particularly significant was the high rate of infections and fistulas [1]. They showed that at that time it was not clear which positions of the meshes related to the material were possible. The infection rate reported in the older papers is higher than in the papers published in the last 3 years [8–12]. Obviously, surgeons are gaining experience and are able to manage the problems better. Another possibility

11

might be the evolution of new meshes. Ramshaw et al. [13] and Stoppa [14] have had very high rates of wound infections, 15–25% (⊡ Table 11.1). In the last years, open mesh repairs have usually been associated with a lower rate of wound infections, 0.6–7% [4, 15–17]. But the main topic of these papers is usually not the infection rate. Mesh infections and the rate of mesh removal must be mentioned, although this topic is difficult to discuss because data on this are not available in every study. Finan et al. [16] found some risk factors for infection: immunosuppression, smoking, intraoperative bowel injury, bowel resection emergency procedures, complicated hernia surgery (incarcerated, obstructed, or strangulated), and operating time. The variation in rates among different hospitals reported in this paper is very interesting– from 1% to 9%. The mesh infection rate was between 0.3% and 6%. So the rate of mesh infection differed, and not every infected mesh was removed, but the data on this problem are very sparse [16].

Tailored Incisional Hernia Surgery – Our Results In our experience since 1996 of using a tailored concept for all operations with mesh (494 of 798),

⊡ Table 11.1. Literature overview of mesh infections in open incisional hernia treatment (minimum 100 cases) First author

Year

N

Wound infections (%)

Mesh infections (%)

Mesh removal (%)

Iannitti [15]

2008

455

0.3

0.3

?

Lammers [17]

2008

774

7

2

0.5

Israelsson [4]

2006

349

9.6

Mahmoud Uslu [18]

2006

291

3.3

0.6

Finan [16]

2005

1505

5

?

Conze [7]

2005

165

17.8

-

Basoglu [32]

2004

264

21.5

2 fistulas

McGreevy [9]

2003

71

8.4

Korenkov [30]

2002

160

13

Ramshaw [13]

1999

174

15.5

6

Stoppa [14]

1989

368

15

ß

?

2

6

82

11

Chapter 11 · Mesh Infection Following Hernia Repair: A Frequent Problem?

we have had a general wound infection rate of 8.9%. For intraperitoneal onlay mesh (IPOM) repair (222 operations), we have had a mesh infection rate of 4%, and only 2.3% of the meshes were removed (only expanded polytetrafluoroethylene, or ePTFE, meshes must be removed). In the onlay repair group (223 operations), we have had a 2.2% mesh infection rate, and just one of 223 meshes had to be removed. We have seen no fistula formation and no intraperitoneal abscesses (⊡ Table 11.2). The rate of fistula to the bladder, colon, or other intestinal organs is very rarely reported in the literature, usually occurring when meshes were used that should not be placed intraperitoneally (heavyweight meshes without a composite structure, polypropylene and polyester). The data on mesh removal are also very rare. We know that infected ePTFE is very difficult to handle, but in our experience, not every infected mesh must be removed in open hernia surgery. Infected polyester meshes are quite difficult to handle, but lightweight polypropylene meshes are not especially difficult to treat. In general, they do not need to be removed. Mahmoud Uslu et al. described only two cases of 291 patients (modified onlay technique) in which it was necessary to reoperate and remove the mesh, whereas the infection rate was 2.7% [18]. The wound infection rate in the study of Conze et al. [7] was very high, up to 18%, with one-third of the affected patients needing surgery. The authors did not define mesh infection, but these must have been deep infections; however, mesh removal was not necessary. At least, there was no significant

difference between composite and regular meshes. All patients had sublay repair (⊡ Table 11.1).

Wound and Mesh Infections in Laparoscopic Hernia Repair One of the main advantages of laparoscopic IPOM is the lower mesh infection rate. The wound infection rate is about 2%, and the mesh infection rate is between 1% and 5%. But one point is very important: Quite often, the data on IPOM are based on a lot of very easy umbilical and epigastric hernias; the patients whose procedures were converted are not included in these data. Also, when a bowel injury is reported, it is not clear whether this means a mesh infection. One of the authors, Finan, stated, »This study had an 8% rate of laparoscopic hernia repairs with a 3.3% wound infection rate compared to a 4.5% rate in open permanent mesh repairs, demonstrating no meaningful difference« [16]. Berger, who reports on only incisional hernia repairs without any selection, has a very low rate of mesh and wound infections–about 1%. We have seen no wound infections but saw one mesh infection caused by an unknown bowel leakage with peritonitis [9, 19–24] (⊡ Table 11.3).

Infections in Inguinal Hernia Repair In almost all studies, infection occurring with an open and laparoscopic inguinal hernia repair is no problem. Mesh infections are very rare, so they are

⊡ Table 11.2. Our data from 1986 to 2008: infection rates (IPOM intraperitoneal onlay mesh) N

Wound infections (%)

Mesh infections (%)

Mesh removal (%)

Unknown bowel injury (%)

Incisional hernia total

798

8.9

1.9

0.9

0.1

With mesh

494

6.2

2.8

1.2

0.2

IPOM

222

6.8

4

2.3

0

Onlay

223

7

2.2

0.4

0

Laparoscopic IPOM

49

0

2

2

2

11

83 Chapter 11 · Mesh Infection Following Hernia Repair: A Frequent Problem?

usually not reported; that is why we looked for a large prospective series. In the years 1991 to 1999 in the North Rhine area of Germany, there was a program to collect all the data on inguinal hernia repair. Nearly 200,000 operations were documented. In the data collection, we discovered that the postoperative complication rate was much higher in general than in randomised studies [3, 25–29]: We found a complication rate of between 5.1% and 9.7%. This

rate decreased as the laparoscopic management of hernias increased up to 29%. The seroma rate was between 3% and 5%, but there were documented wound infections of 0.79–1.55%, swelling of the scrotum in about 0.7%, and swelling of the testes in 0.24–0.52% (as a sign for testicular atrophy in the future). The reoperation rate was a bit higher than 1%. These patients are always at risk for a mesh infection. The mortality rate was 0.1% (⊡ Table 11.4).

⊡ Table 11.3. Literature overview of mesh infections in laparoscopic ventral hernia therapy First author

Year

N

Wound infections (%)

Mesh infections (%)

Mesh removal (%)

Ferrari [20]

2007

99

1

1

1

Heniford [21]

2000

407

1.23

0.98

0.98

McGreevy [9]

2003

65

–

4.6

4.6

Olmi [31]

2007

85

–

1

1

LeBlanc [23]

2000

100

2

1

1

Berger [22]

2002

150

1.3

1

1

Lammers [own data]

2008

49

0

2

2

⊡ Table 11.4. Results of inguinal hernia surgery in the North Rhine district of Germany [3] Year

1999

1998

1997

1996

1995

1994

1993

1992

1991

Total

Patients

19,266

18,619

19,732

20,940

19,646

19,907

19,740

18,738

17,605

173,923

Operations

22,015

21,162

22,212

23,245

21,639

21,888

21,354

20,203

19,000

192,718

Postoperative complications (%)

5.9

5.6

5.5

5.1

6.4

7.6

7.9

8.1

9.7

Reoperation (%)

1.10

1.16

1.13

1.12

1.17

1.48

1.42

–

–

Seroma, haematoma (%)

3.85

3.27

3.11

2.8

3.54

4.46

4.39

4.27

5.08

Wound infection (%)

0.89

0.84

0.90

0.79

1.19

1.31

1.51

1.48

1.55

Swelling of scrotum (%)

0.55

0.58

0.56

0.44

0.58

0.75

0.77

0.74

0.81

Swelling of testes (%)

0.26

0.28

0.32

0.24

0.34

0.53

0.49

0.42

0.52

–

84

Chapter 11 · Mesh Infection Following Hernia Repair: A Frequent Problem?

Discussion

11

The problem of mesh infection in hernia repair does not occur very often, but when it does, there is always the question of whether the mesh has to be removed. Some studies found that in the case of an infection with ePTFE, the mesh should be removed. Most of the meshes that were developed within the last 7 years (light meshes, composite meshes) did not have this problem. Fistula formation is not so rare when the wrong mesh is used intraperitoneally; the rate could be as high as 3.5% [1, 19]. Therefore, it is very important to use only approved meshes intraabdominally and perhaps even avoid intraperitoneal meshes. Mesh infection in laparoscopic hernia repair is often associated with mesh removal, but the data are very sparse. When studying the literature, it is very difficult to discover the complication rates because many studies involved a mixture of ventral and incisional hernias. When looking back at older data, it can be seen that incisional hernia treatment formerly had a high wound infection rate. When prophylactic antibiotics were used, the rate decreased to 5–7%. The infection rate seems to be higher in large series; the studies on antibiotics suggest this [25–29]. But the incidence of mesh-associated infections, including fistula formation, is not clear in inguinal hernia repair. In general, a higher complication rate is noted when many hospitals are involved in a study. Deep infection, including infection of the mesh, has a high risk of recurrence and reoperation. In the future, more studies are necessary to look for the advantages related to laparoscopic incisional hernia repair.

4. 5.

6.

7.

8.

9.

10.

11. 12. 13.

14. 15.

16.

17. 18.

References 19. 1. Leber GE, Gar JL, Aleander AL, et al. Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 1998; 133:378–382 2. Lammers BJ, Voos S, Witt M, Goretzki PE. Results of conventional mesh-augmented incisional hernia repair. Chir Gastroenterol 2003; suppl 2:24–28 3. Lammers BJ, Meyer HF, Huber HG, et al. Developments in inguinal hernia surgery based on newly introduced inter-

20.

21.

vention techniques in the North Rhine district. Chirurg 2001; 72:448–452 Israelsson LA, Smedberg S, Montomery A, et al. Incisional hernia repair in Sweden 2002. Hernia 2006; 10:258–261 Perez A, Roxas MF, Hilvano SS. A randomized, doubleblind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy. J Am Coll Surg 2005; 200:393–398 Yerdel MA, Akin EB, Dolalan S, et al. Effect of singledose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh. The randomized, double-blind, prospective trial. Ann Surg 2001; 233:26–33 Conze J, Kingsnorth AN, Flament JB, et al. Randomized clinical trial comparing lightweight composite mesh with polyester or polypropylene mesh for incisional hernia repair. Br J Surg 2005; 92:1488–1493 Lammers BJ, Goretzki PE, Witt M, Röher WM. e-PTFE IPOM versus onlay-repair–results of a prospective randomised controlled trial. Chir Forum 2001; 30:563–566 McGreevy JM, Goodney PP, Birkmeyer CM, et al. A prospective study comparing the complication rates between laparoscopic and open ventral hernia repairs. Surg Endosc 2003; 17:1778–1780 Arroyo A, Garcia P, Pérez F, et al. Randomized clinical trial comparing suture and mesh repair of umbilical hernia in adults. Br J Surg 2001; 88:1321–1323 Cassar K, Munro A. Surgical treatment of incisional hernia. Br J Surg 2002; 89:534–545 Langer C, Liersch T, Kley C, et al. 25 Jahre Erfahrung in der Narbenhernienchirurgie. Chirurg 2003; 74:638–645 Ramshaw BJ, Esartia P, Schwab J, et al. Comparison of laparoscopic and open ventral herniorrhaphy. Am Surg 1999; 65:827–832 Stoppa RE. The treatment of complicated groin and incisional hernias. World J Surg 1989; 13:545–554 Iannitti DA, Hope WW, Norton HJ, et al. Technique and outcomes of abdominal incisional hernia repair using a synthetic composite mesh: a report of 455 cases. J Am Coll Surg 2008; 206:83–88 Finan KR, Vick CC, Kiefe CI, Neumayer L, Hawn MT. Predictors of wound infection in ventral hernia repair. Am J Surg 2005; 190:676–681 Lammers BJ, Goretzki PE, Otto T. New aspects in hernia surgery. Urologe 2005; 44:774–779 Mahmoud Uslu HY, Erkek AB, Cakmak A, et al. Incisional hernia treatment with polypropylene graft: results of 10 years. Hernia 2006; 10:380–384 Benhidjeb T, Bärlehner E, Anders S. Laparoscopic incisional hernia repair. Chir Gastroenterol 2003; 19(suppl):16–22 Ferrari GC, Mirando A, Di Lernia S, et al. Laparoscopic repair of incisional hernia: outcomes of 100 consecutive cases comprising 25 wall defects larger than 15 cm. Surg Endosc 2008; 22:1173–1179 Heniford BT, Park A, Ramshaw BJ, Voeller G. Laparoscopic ventral and incisional hernia repair in 407 patients. J Am Coll Surg 2000; 190:645–650

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22. Berger D, Bientzle M, Müller A. Postoperative complications after laparoscopic incisional hernia repair. Surg Endosc 2002; 16:1720–1723 23. LeBlanc KA, Booth WV, Whitaker JM, Bellanger DE. Laparoscopic incisional and ventral herniorrhaphy in 100 patients. Am J Surg 2000; 180:193–197 24. O’Dwyer PJ, Kingsnorth AN, Molloy RG, et al. Randomized clinical trial assessing impact of a lightweight or heavyweight mesh on chronic pain after inguinal hernia repair. Br J Surg 2005; 92:166–170 25. Sanabria A, Dominguez LC, Valdivieso E, Gabriel G. Prophylactic antibiotics for mesh inguinal hernioplasty: a meta-analysis. Ann Surg 2007; 245:392–396 26. Kuzu M, Hazinedaroglu S, Dolalan S, et al. Prevention of surgical site infection after open prosthetic inguinal hernia repair: efficacy of parenteral versus oral prophylaxis with amoxicillin-clavulanic acid in a randomized clinical trial. World J Surg 2005; 29:794–799 27. Perez A, Roxas MF, Hilvano SS. A randomized, doubleblind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy. J Am Coll Surg 2005; 200:393–398 28. Yerdel MH, Akin EB, Dolalan S, et al. Effect of singledose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh. The randomized, double-blind, prospective trial. Ann Surg 2001; 233:26–33 29. Terzi C, Kilic D, Ünek T, et al. Single-dose oral ciprofloxacin compared with single-dose intravenous cefazolin for prophylaxis in inguinal hernia repair: a controlled randomized clinical study. J Hosp Infect 2005; 60:340–347 30. Korenkov M, Sauerland S, Arndt M, et al. Randomized clinical trial of suture repair, polypropylene mesh or autodermal hernioplasty for incisional hernia. Br J Surg 2002; 89:50–56 31. Olmi S, Scaini A, Cesana GC, et al. Laparoscopic versus open incisional hernia repair. An open randomized controlled study. Surg Endosc 2007; 21:555–559 32. Basoglu M, Yildirgan MI, Yilmaz I, et al. Late complications of incisional hernias following prosthetic mesh repair. Acta Chir Belg 2004; 104:425–428 33. Bingener J, Buck L, Richards M, et al. Long-term outcomes in laparoscopic vs open ventral hernia repair. Arch Surg 2007; 142:562–567

Discussion Read: You mentioned bacteria. Are there any viral infections of mesh? Lammers: It may be possible, but I have never seen it, and I have never heard about this. Schumpelick: Do you know where the bacteria come from?

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Lammers: First of all, we know that patients who

have had an infection in former times from the first operation—for example, for bowel with anastomosis leakage, they have bacteria even years after the first operation in the wound. That’s the advantage of laparoscopic hernia repair because you don’t open the same wound again. On the other hand, during open hernia repair there is the possibility to bring bacteria inside the wound, such as from the patient’s skin. But there are no studies available on this problem at the moment.

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Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery H. W. Hopf

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Chapter 12 · Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery

Introduction

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Despite major advances in the management of patients undergoing surgery–including aseptic technique, prophylactic antibiotics, and advances in surgical approaches such as laparoscopic surgery– surgical wound infection remains among the most common complications of surgery [1]. Wound complications are associated with prolonged hospitalization and increased resource consumption. More than 300,000 surgical site infections occur each year in the United States at an estimated cost of more than $1 billion [1]. A growing body of literature supports the concept that patient factors are a major determinant of wound outcome following surgery. Comorbidities such as diabetes and cardiac disease clearly contribute, but environmental stressors as well as the individual’s response to stress are equally important. In particular, wounds are exquisitely sensitive to hypoxia, which is both common and preventable. Perioperative management can be adapted to promote postoperative wound healing and resistance to infection. Along with aseptic technique and prophylactic antibiotics, maintenance of perfusion and oxygenation of the wound is paramount. There is strong clinical evidence that once perfusion is assured, the addition of increased inspired oxygen substantially reduces surgical site infections in at-risk patients. It is becoming clear that the intraoperative care of patients has repercussions far into the postoperative period. The impact of anesthetic technique on postoperative pain, perioperative myocardial ischemia, and vascular graft patency is now well established. Similarly, anesthetic technique can be adapted to promote postoperative wound healing and resistance to infection. The most important factors include temperature management, increased arterial oxygen tension (PaO2), pain control, fluid management, and, as has been long recognized, appropriate sterile technique and administration of prophylactic antibiotics. All but the last relate particularly to maintaining perfusion and oxygenation of the wound. Even when the best care possible is provided, surgical wounds may become infected or fail to heal. The progress of wounds healing by secondary

intention can also be optimized. The most important factors include attention to perfusion and oxygenation, as with acute wounds; moist wound care; control of bacterial load; nutrition; edema control; and prevention of ongoing trauma.

Wound Repair Injury damages the local circulation and causes platelets to aggregate and release a variety of substances, including chemoattractants and growth factors. The initial result is coagulation, which prevents exsanguination, but also widens the area that is no longer perfused. Inflammatory cells (polymorphonuclear leukocytes immediately and macrophages by 24–48 h) migrate to the wound and are activated in response to endothelial integrins, fibrin, lactate, hypoxia, foreign bodies, and growth factors. In turn, macrophages and lymphocytes produce more growth factors and lactate [2]. Activated inflammatory cells consume oxygen at a high rate, and, coupled with the impaired microcirculation, this results in hypoxia, especially at the center of the wound [3]. Lactate is produced both anaerobically and aerobically, and this results in concentrations of 5–15 mM even in well-oxygenated wounds. Lactate is a strong stimulus for collagen secretion and angiogenesis [4, 5]. Antiinflammatory steroids impair healing by suppressing inflammation at this step. Angiogenesis is required to replace the injured microcirculation. Platelets release a number of angiogenic factors, including platelet-derived growth factor, insulin-like growth factor 1, and others. Angiogenic growth factor levels remain high because of continued production by macrophages and fibroblasts (particularly of fibroblast growth factor and vascular endothelial growth factor) in response to hypoxia and lactate, among other things [6]. The capillary endothelial response to angiogenic agents (i.e., migration into the wound, tubule formation, and connecting to sources of blood flow) requires oxygen, so angiogenesis progresses proportionally to blood perfusion and arterial PO2 [7]. New blood vessels grow into matrix that is produced by fibroblasts. Fibroblasts replicate and migrate mainly in response to growth factors and

89 Chapter 12 · Patient Factors as a Major Determinant of Wound Outcome and Infection

chemoattractants. Lactate and some growth factors induce collagen mRNA synthesis and procollagen production. Posttranslational modification by prolyl and lysyl hydroxylases is required to allow collagen peptides to aggregate into triple helices. Collagen can be exported from the cell only when it is in this triple helical structure. The helical configuration is also primarily responsible for tissue strength. The activity of the hydroxylases is critically dependent on vitamin C and tissue oxygen tension [8]. Wound strength, which results from collagen deposition, is, therefore, highly vulnerable to wound hypoxia. Angiogenesis and extracellular matrix (primarily collagen) production are closely linked. Fibroblasts cannot produce mature collagen in the absence of mature blood vessels that deliver oxygen to the site. On the other hand, new blood vessels cannot mature without a strong collagen matrix. Mice kept in a hypoxic environment (13% inspired oxygen) develop some new blood vessels in a test wound, but these vessels are immature, with little surrounding matrix, and demonstrate frequent areas of hemorrhage [9]. Epithelial cells move and replicate in response to growth factors and oxygen tension, and epithelization occurs most rapidly in hydrated, welloxygenated tissue [10]. Disruption of the normal skin barrier requires that wounds have the ability to clear foreign material and resist infection. Nonspecific phagocytosis and intracellular killing are the major pathways activated in wounds [11]. Conversion of oxygen to superoxide in phagocytic vacuoles is responsible for the first step in nonspecific intracellular killing, so resistance to infection is critically impaired by wound hypoxia and becomes more efficient as PO2 increases even to very high levels (500– 1,000 mmHg) [12].

Wound Perfusion and Oxygenation Wound complications include failure to heal, infection, and excessive scarring or contracture. Rapid repair has the least potential for infection and excess scarring. Repair proceeds most rapidly when wound oxygen levels are high, and this is

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achieved only by maintaining perfusion of injured tissue [13]. Ischemic or hypoxic tissue, on the other hand, is easily infectable and heals poorly, if at all. Wound tissue oxygenation depends on the vascular anatomy, the degree of vasoconstriction, and arterial PO2. Wound tissue oxygenation is complex and depends on the interaction of blood perfusion, arterial oxygen tension, hemoglobin (Hb) dissociation conditions, carrying capacity, mass transfer resistances, and local oxygen consumption. The standard teaching that oxygen delivery depends more on hemoglobin-bound oxygen (oxygen content) than on arterial PO2 may be true of working muscle, but it is not true of wound healing. In muscle, intercapillary distances are small, and oxygen consumption is high. In subcutaneous tissue, on the other hand, intercapillary distances are large, and oxygen consumption is relatively low [14]. In uninjured subcutaneous tissue, the intercapillary distance is greater than that in muscle and other highly perfused organs. In wounds, where the microvasculature is damaged, diffusion distances increase by an order of magnitude. Peripheral vasoconstriction further increases diffusion distance [3]. The driving force of diffusion is partial pressure. Hence, a high PO2 is needed to force oxygen into injured and healing tissues, particularly in subcutaneous tissue, fascia, tendon, and bone. Although oxygen consumption is relatively low in wounds, it is consumed by processes that require oxygen at a high concentration. Inflammatory cells use little oxygen for respiration, producing energy largely via the hexose-monophosphate shunt [12]. Most of the oxygen consumed in wounds is used for oxidant production (bacterial killing), collagen synthesis, angiogenesis, and epithelization. The rate constants for oxygen for these components of repair all fall within the physiologic range of 25–100 mmHg [10, 12, 15–18]. This means that the rate at which repair proceeds varies according to tissue PO2 from zero to at least 250 mmHg. In vitro fibroblast replication is optimal at a PO2 of about 40–60 mmHg. These in vitro observations are clinically relevant. »Normal« subcutaneous PO2, measured in test wounds in uninjured, euthermic, euvolemic volunteers breathing room air,

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Chapter 12 · Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery

is 65±7 mmHg [19]. Thus, any degree of hypoxia may impair immunity and repair. In surgical patients, the rate of wound infections is inversely proportional [20], while collagen deposition is directly proportional [21] to postoperative subcutaneous wound tissue oxygen tension. High oxygen tensions (>100 mmHg) can be reached in wounds but only if perfusion is rapid and arterial PO2 is high [13, 22]. This is because 1) subcutaneous tissue serves a reservoir function, so there is normally flow in excess of nutritional needs, and 2) wound cells consume relatively little oxygen, about 0.7 ml/100 ml of blood flow at a normal perfusion rate [14, 23]. At high levels of PaO2, this small volume can be carried by plasma alone. Contrary to popular belief, therefore, oxygen-carrying capacity (i.e., hemoglobin concentration) is not particularly important to wound healing provided that perfusion is normal [24]. Wound PO2 and collagen synthesis remain normal in individuals who have hematocrit levels as low as 15–18% provided they can appropriately increase cardiac output and vasoconstriction is prevented. Peripheral vasoconstriction, which results from central sympathetic control of subcutaneous vascular tone, is probably the most frequent and clinically the most important impediment to wound oxygenation. Subcutaneous tissue is both a reservoir to maintain central volume and a major site of thermoregulation. There is little local regulation of blood flow, except by local heating [22, 25]. Therefore, subcutaneous tissue is particularly vulnerable to vasoconstriction. Sympathetically induced peripheral vasoconstriction is stimulated by cold, pain, fear, and blood volume deficit [26, 27] and by various medications, including nicotine (smoking) [19], beta adrenergic antagonists, and alpha-1 agonists, all commonly present in surgical situations. Prevention and correction of hypothermia [28] and blood volume deficits [29] have been shown to decrease wound infections and increase collagen deposition in patients undergoing major abdominal surgery. Subcutaneous tissue oxygen tension is significantly higher in patients with good pain control than in those with poor pain control after knee surgery [30]. Stress also causes wound hypoxia and significantly impairs wound healing and resistance to infection [31, 32].

These effects are clearly mediated, at least in major part, by raising the partial pressure of oxygen in the injured tissue. Greif et al. demonstrated in a randomized, controlled, double-blind trial that in warm, wellhydrated patients (n=500) with good pain control (that is, in well-perfused patients) undergoing major colon surgery, administration of 80% vs. 30% oxygen intraoperatively and for the first 2 h postoperatively significantly reduced the wound infection rate by 50% [33]. Belda et al. [34] replicated these results–noting a significant 40% reduction in surgical site infection–in a randomized, controlled, double-blind trial in 300 colon surgery patients randomized to 80% vs. 30% oxygen intraoperatively and for the first 6 h postoperatively. Surgical and anesthetic management was standardized and intended to support optimal perfusion. Myles et al. demonstrated a significant reduction in major postoperative complications, as well as specific wound infections, in 2,050 major surgery patients randomized to 80% oxygen in 20% nitrogen vs. 30% oxygen in 70% nitrous oxide intraoperatively [35]. A smaller (n=165) randomized, controlled study by Pryor et al. [36] demonstrated a doubling of surgical site infection in patients randomized to 80% vs. 35% oxygen intraoperatively. The study had a number of methodological flaws, but, more importantly, the two groups of patients were not equivalent, which likely explained the increase in infections seen in the 80% oxygen group. Thus, there is substantial evidence that use of high inspired oxygen intraoperatively and the administration of supplemental oxygen postoperatively in well-perfused patients undergoing major abdominal surgery will reduce the risk of wound infection. Concerns about the risk of oxygen toxicity, including pulmonary fibrosis and atelectasis, have limited adoption of high inspired oxygen. Oxygen toxicity is not a risk in the short term (less than days) and therefore is not pertinent in the operating room. Some degree of atelectasis is inevitable in all patients undergoing major surgery. Akca et al. [37] demonstrated similar degrees of atelectasis in colon surgery patients randomized to 80% vs. 30% oxygen (balance nitrogen) intraoperatively.

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Myles et al. found that high inspired nitrous oxide caused more atelectasis than high inspired oxygen. Use of positive end expiratory pressure appears to abrogate the problem of atelectasis [38]. Thus, these issues should not limit the use of high inspired oxygen. Contraindications to the use of FiO2 >0.8 include prematurity (retrolental fibroplasias), recent (possibly lifetime) bleomycin administration, use of cautery in the airway or other procedures in which pulmonary or laryngeal oxygen may leak into the field, and, possibly, acute pulmonary conditions. Delivery of antibiotics also depends on perfusion. Parenteral antibiotics given so that high levels are present in the blood at the time of wounding clearly diminish, but do not eliminate, wound infections [39]. In one-third of all wound infections, the bacteria cultured from the wound are sensitive to the prophylactic antibiotic given to the patient, even when the antibiotics were given according to standard procedure. The vulnerable third of patients appear to be the hypoxic and vasoconstricted group.

Intraoperative Management All anesthetics tend to cause hypothermia 1) by causing vasodilation, which redistributes heat from core to periphery in previously vasoconstricted patients and increases heat loss, and 2) by decreasing heat production [40]. Vasoconstriction is uncommon intraoperatively, as the threshold for thermoregulatory vasoconstriction is decreased, but it is often severe in the immediate postoperative period, when anesthesia is discontinued and the thermoregulatory threshold returns to normal in the face of core hypothermia. The onset of pain with emergence from anesthesia adds to this vasoconstriction. Maintenance of normothermia intraoperatively has been shown to decrease the wound infection rate by two-thirds in patients undergoing colon surgery [28]. Rapid rewarming of hypothermic patients in the postanesthesia care unit (PACU) also appears to be effective [41]. Maintenance of a high room temperature or forced air warming before, during, and after the operation are significantly more effective than other meth-

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ods of warming such as circulating water blankets placed under the patient and humidification of the breathing circuit [42]. Preoperative systemic (forced air warmers) or local (warming bandages) warming techniques have also been shown to decrease wound infections, even in clean, low-risk surgeries such as breast surgery and inguinal hernia repair [43]. Surgical stress results in increased intravenous fluid requirements. Inflammatory mediators cause both vasodilation and an increase in vascular permeability [44]. Other known causes of perioperative hypovolemia or fluid loss include preoperative mechanical bowel preparation, lack of oral intake, fever, preexisting medical conditions, medications such as diuretics, and surgical fluid losses, including evaporation and blood loss. Optimizing the perioperative fluid administration remains a controversial challenge. Estimates of blood loss, third-space fluid losses, and maintenance requirements are inaccurate and may lead to either overreplacement or underreplacement. Currently, most practitioners rely on their clinical acumen, vital signs such as heart rate and blood pressure, and urine output to manage perioperative fluids. Due to the compensatory action of peripheral vasoconstriction, surgical patients can be markedly hypovolemic without a change in any of these variables [13, 21, 45]. Unfortunately, this peripheral vasoconstriction shunts blood away from the skin, increases wound hypoxemia, and increases the risk of surgical wound infection [20]. Current best recommendations include replacing fluid losses based on standard recommendations for the type of surgery, replacing blood loss, and replacing other ongoing fluid losses (e.g., high urine output due to diuretic or dye administration, hyperglycemia, or thermoregulatory vasoconstriction). Pain control should be addressed intraoperatively so that patients do not have severe pain upon emergence from anesthesia. Achieving the goal is more important than the technique used to do so. Although regional anesthesia/analgesia may provide superior pain relief, the effects of specific analgesic regimens on wound outcome have not yet been studied.

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Postoperative Management

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Wounds are most vulnerable in the early hours. Although antibiotics lose their effectiveness after the first hours, natural wound immunity (oxygenrelated) lasts longer [46]. Even a short period of vasoconstriction during the first day is sufficient to reduce oxygen supply. Correction and prevention of vasoconstriction in the first 24-48 h after surgery will have significant beneficial effects. All vasoconstrictive stimuli must be corrected simultaneously to allow optimal healing. Volume is the last to be corrected because vasoconstriction for other reasons induces diuresis and renders the patient hypovolemic (peripherally, not centrally). Assessing perfusion, especially in the PACU, is critical. Unfortunately, urine output is a poor and often misleading guide to peripheral perfusion [47]. Markedly low output may indicate decreased renal perfusion, but normal or even high urine output has little correlation to wound/tissue PO2. Many factors commonly present in the perioperative period, including hyperglycemia, dye administration, thermoregulatory vasoconstriction, adrenal insufficiency, and various drugs, may cause inappropriate diuresis in the face of mild hypovolemia. Physical examination of the patient is a better guide to dehydration and vasoconstriction. Vasoconstriction can be determined by a capillary return time of more than 1.5 s at the forehead and more than 5 s over the patella. Eye turgor is another good measure of hydration. Finally, patients can usually distinguish thirst from a dry mouth. Skin should be warm and dry. When excessive tissue fluids have accumulated, diuresis should be undertaken gently so that transcapillary refill can maintain blood volume. This applies to patients who need renal dialysis as well. The average dialysis patient vasoconstricts sufficiently to lower tissue PO2 by 30% or more during dialysis and needs about 24 h for vasomotor tone and wound/tissue PO2 to return to normal [48]. Fluid losses from the vascular system are not necessarily replaced from the tissues as rapidly as they are sustained. Tissue edema may be the price paid for adequate intravascular volume. Edema

increases intracapillary distance, so there may be a delicate balance between excessive edema and peripheral vasoconstriction (which worsens the hypoxia caused by edema).

Care of Wounds Healing by Secondary Intention Even with appropriate perioperative management, some wounds become infected or fail to heal. Frequently this may result from other causes of impaired perfusion, such as obesity, prior radiation to the area, arterial insufficiency, or excessive edema. It may also result from other problems such as malnutrition, overwhelming contamination, or ongoing trauma. If it is a simple case of infection, the wound will generally heal rapidly by secondary intention with just attention to basic care. If other complicating factors are involved, it may take more effort to achieve healing. In either case, the most modern and advanced healing devices will not succeed if proper care is not instituted, so attention to basic proper wound care is crucial to ensure success: 1. Reduce the bacterial load. The best way to achieve this is to wash the wound gently with mild soap in a warm shower. All open wounds are contaminated with bacteria. Most bacterial contamination comes from bacteria normally resident on the skin. A shower provides the volume to wash away the bacteria; rinsing with normal saline does not provide adequate volume. Moreover, saline is generally kept refrigerated or at room temperature and thus will tend to induce local vasoconstriction, whereas a warm shower will tend to induce local vasodilation. Mild soap provides sufficient detergent effect to assist in dislodging bacteria. Antibacterial agents, including antibacterial soaps, Betadine, bleach, Dakin’s solution, hydrogen peroxide, and alcohol, are effective at reducing bacterial load, but they do so at the cost of inactivating white cells and harming granulating tissue. Thus, wounds treated with these agents are very clean but frequently demonstrate minimal evidence of healing (granulation tissue).

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2. Maintain a moist wound environment. Moist wounds heal about 50% faster than dry ones [49, 50]. Any number of products may provide the proper environment, depending on the wound. Traditional wet-to-damp dressings should be replaced as the standard of care and essentially never used. They are less cost-effective than any other dressing on the market because they have minimal ability to manage exudates and they induce maceration of the surrounding skin, thereby potentially actually enlarging the wound; they pull off granulation tissue as they debride necrotic tissue and slough, thus prolonging healing. They also provide no protection against bacterial contamination (nonocclusive), must be changed three times a day (TID), and cause more discomfort. Although a single sheet of gauze is inexpensive compared with a typical $10–20 modern dressing, more than one piece of gauze is used with each dressing change, and the dressing must be changed TID, thus raising the supply cost at least as high as more sophisticated dressings that are only changed daily or less often. The labor costs of wetto-damp dressings are therefore also higher. Moreover, home care nurses cannot provide TID dressing changes, which may delay hospital discharge. Finally, given that dressing changes often cause discomfort, less frequent changes are clearly a benefit. So use whatever you want, but don’t use wet to damp! Of note, gauze impregnated with a nonevaporating substance such as Aquaphor, silver sulfadiazine, or a hydrogel does make an excellent filler for deeper wounds. 3. Pay attention to nutrition. Recent intake (7 days) is most important [51]. Be aware of a patient’s NPO status leading to missed meals. Key elements include protein, which is required to make the extracellular matrix but is lost in potentially large quantities from exudative wounds, and vitamin C, an essential cofactor of prolyl hydroxylase (a central enzyme in collagen posttranslational modification) as well as essential for proper neutrophil function. The type of protein is relatively unimportant, although the amino acid arginine im-

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proves wound healing at pharmacologic (more than nutritional) levels [52]. Arginine-containing protein supplements are available, and arginine capsules can be obtained at health food stores. Vitamin A and zinc deficiencies impair wound healing, and these should be repleted. A 10-day course (25,000 IU vitamin A and 220 mg zinc daily) is sufficient, as both may be toxic in excess. Vitamin A specifically reverses impaired healing resulting from steroids [53, 54]. Topical vitamin A and D ointment (sold for diaper rash over the counter) applied once daily works well. 4. Pay attention to perfusion. Patients should be instructed to quit smoking, drink plenty of fluids, manage their pain aggressively, and keep their wound covered or insulated for warmth. Stress reduction is also likely to be beneficial.

Summary In patients with moderate to high risk of surgical site infection, surgeons and anesthesiologists have the opportunity to enhance wound healing and prevent wound infections by simple, inexpensive, and readily available means [55, 56]. Intraoperatively, appropriate antibiotic use, prevention of vasoconstriction (volume, warming), and maintenance of a high PaO2 (300–500 mmHg) are key. Postoperatively, the focus should remain on preventing vasoconstriction through pain relief, warming, and adequate volume administration in the PACU.

References 1. Kaye, K.S., et al., Preoperative drug dispensing as predictor of surgical site infection. Emerg Infect Dis, 2001. 7(1): pp. 57–65 2. Dvonch, V.M., et al., Changes in growth factor levels in human wound fluid. Surgery, 1992. 112(1): pp. 18–23 3. Silver, I.A., Cellular microenvironment in healing and nonhealing wounds., in Soft and hard tissue repair, T.K. Hunt, R.B. Heppenstall, and E. Pines, eds. 1984, Praeger: New York. pp. 50–66 4. Hunt, T.K., et al., Studies on inflammation and wound healing: Angiogenesis and collagen systhesis stimulated

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Chapter 12 · Patient Factors as a Major Determinant of Wound Outcome and Infection After Surgery

in vivo by resident and activated wound macrophages. Surgery, 1984. 96: pp. 48–54 Jensen, J.A., et al., Effect of lactate, pyruvate and pH on secretion of angiogenesis and mitogenesis factors by macrophages. Lab Invest, 1986. 54: pp. 574–578 Schultz, G. and M. Grant, Neovascular growth factors. Eye, 1991. 5: pp. 170–180 Knighton, D.R., I.A. Silver, and T.K. Hunt, Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery, 1981. 90(2): pp. 262–720 Prockop, D.J., et al., The biosynthesis of collagen and its disorders (first of two parts). N Engl J Med, 1979. 301(1): pp. 13–23 Hunt, T.K., et al., Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxid Redox Signal, 2007. 9(8): pp. 1115–1124 Medawar, P.S., The behavior of mammalian skin epithelium under strictly anaerobic conditions. Q J Microsc Sci, 1947. 88: p. 27 Babior, B.M., Oxygen-dependent microbial killing by phagocytes. N Engl J Med, 1978. 198: pp. 659–668 Allen, D.B., et al., Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg, 1997. 132(9): pp. 991–996 Gottrup, F., et al., Directly measured tissue oxygen tension and arterial oxygen tension assess tissue perfusion. Crit Care Med, 1987. 15(11): pp. 1030–1036 Evans, N.T.S. and P.F.D. Naylor, Steady states of oxygen tension in human dermis. Respir Physiol, 1966. 2: pp. 46–60 Edwards, S., M. Hallett, and A. Campbell, Oxygen-radical production during inflammation may be limited by oxygen concentration. Biochem J, 1984. 217: pp. 851–854 Hutton, J.J., A.L. Tappel, and S. Udenfriend, Cofactor and substrate requirements of collagen proline hydroxylase. Arch Biochem Biophys, 1967. 118: pp. 231–240. Myllyla, R., L. Tuderman, and K.I. Kivirikko, Mechanism of the prolyl hydroxylase reaction. 2. Kinetic analysis of the reaction sequence. Eur J Biochem, 1977. 80(2): pp. 349–357 DeJong, L. and A. Kemp, Stoicheiometry and kinetics of the prolyl 4-hydroxylase partial reaction. Biochim Biophys Acta, 1984. 787(1): pp. 105–111 Jensen, J.A., et al., Cigarette smoking decreases tissue oxygen. Arch Surg, 1991. 126: pp. 1131–1134 Hopf, H.W., et al., Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg, 1997. 132(9): pp. 997–1004; discussion 1005 Jonsson, K., et al., Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann Surg, 1991. 214: pp. 605–613 Sheffield, C., et al., Centrally and locally mediated thermoregulatory responses alter subcutaneous oxygen tension. Wound Repair Regen, 1996. 4(3): pp. 339–345 Hopf, H., T. Hunt, and J. Jensen, Calculation of subcutaneous tissue blood flow. Surg Forum, 1988. 39: pp. 33–36

24. Hopf, H. and T. Hunt, Does–and if so, to what extent–normovolemic dilutional anemia influence post-operative wound healing? Chirugische Gastroenterologie, 1992. 8: pp. 148–150 25. Rabkin, J.M. and T.K. Hunt, Local heat increases blood flow and oxygen tension in wounds. Arch Surg, 1987. 122(2): pp. 221–225 26. Derbyshire, D. and G. Smith, Sympathoadrenal responses to anaesthesia and surgery. Br J Anaesth, 1984. 56: pp. 725–739 27. Halter, J., A. Pflug, and D. Porte, Mechanism of plasma catecholamine increases during surgical stress in man. J Clin Endocrin Metab, 1977. 45(5): pp. 936–944 28. Kurz, A., et al., Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med, 1996. 334(19): pp. 1209–1215 29. Hartmann, M., K. Jonsson, and B. Zederfeldt, Effect of tissue perfusion and oxygenation on accumulation of collagen in healing wounds. Randomized study in patients after major abdominal operations. Eur J Surg, 1992. 158(10): pp. 521–526. 30. Akça, O., et al., Postoperative pain and subcutaneous oxygen tension [letter]. Lancet, 1999. 354(9172): pp. 41–42 31. Rojas, I.G., et al., Stress-induced susceptibility to bacterial infection during cutaneous wound healing. Brain Behav Immun, 2002. 16(1): pp. 74–84 32. Horan, M.P., et al., Impaired wound contraction and delayed myofibroblast differentiation in restraint-stressed mice. Brain Behav Immun, 2005. 19(3): pp. 207–216 33. Greif, R., et al., Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. Outcomes Research Group. N Engl J Med, 2000. 342(3): pp. 161–167 34. Belda, F.J., et al., Supplemental perioperative oxygen and the risk of surgical wound infection: a randomized controlled trial. JAMA, 2005. 294(16): pp. 2035–2042 35. Myles, P.S., et al., Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology, 2007. 107(2): pp. 221–231 36. Pryor, K.O., et al., Surgical site infection and the routine use of perioperative hyperoxia in a general surgical population: a randomized controlled trial. JAMA, 2004. 291(1): pp. 79–87 37. Akca, O., et al., Comparable postoperative pulmonary atelectasis in patients given 30% or 80% oxygen during and 2 hours after colon resection. Anesthesiology, 1999. 91(4): pp. 991–998 38. Duggan, M. and B.P.P. Kavanagh, Atelectasis in the perioperative patient. Curr Opin Anaesthesiol, 2007. 20(1): pp. 37–42 39. Classen, D., et al., The timing of prophylactic administration of antibiotics and the risk of surgical wound infection. N Engl J Med, 1992. 326(5): pp. 281–286 40. Matsukawa, T., et al., Heat flow and distribution during induction of general anesthesia. Anesthesiology, 1995. 82: pp. 662–673 41. West, J., et al., The effect of rapid postoperative rewarming on tissue oxygen. Wound Repair Regen, 1993. 1(2): p. 93

95 Chapter 12 · Patient Factors as a Major Determinant of Wound Outcome and Infection

42. Kurz, A., et al., Forced-air warming maintains intraoperative normothermia better than circulating water mattresses. Anesth Analg, 1993. 77: pp. 89–95 43. Melling, A.C., et al., Effects of preoperative warming on the incidence of wound infection after clean surgery: a randomised controlled trial. Lancet, 2001. 358(9285): pp. 876–880 44. Holte, K., N.E. Sharrock, and H. Kehlet, Pathophysiology and clinical implications of perioperative fluid excess. Br J Anaesth, 2002. 89(4): pp. 622–632 45. Gosain, A., et al., Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage. Surgery, 1991. 109(4): pp. 523–532 46. Knighton, D.R., B. Halliday, and T.K. Hunt, Oxygen as an antibiotic. A comparison of the effects of inspired oxygen concentration and antibiotic administration on in vivo bacterial clearance. Arch Surg, 1986. 121(2): pp. 191–195 47. Jonsson, K., et al., Assessment of perfusion in postoperative patients using tissue oxygen measurements. Br J Surg, 1987. 74(4): pp. 263–267 48. Jensen, J.A., et al., Subcutaneous tissue oxygen tension falls during hemodialysis. Surgery, 1987. 101(4): pp. 416– 421 49. Winter, G.D., Oxygen and epidermal wound healing. Adv Exp Med Biol, 1977. 94(673): pp. 673–678 50. Hinman, C. and H.I. Maibach, Effect of air exposure and occlusion on experimental human skin wounds. Nature, 1963. 200: pp. 377–378 51. Haydock, D. and G. Hill, Improved wound healing response in surgical patients receiving intravenous nutrition. Br J Surg, 1987. 74: pp. 320–323 52. Barbul, A., et al., Arginine enhances wound healing and lymphocyte immune response in humans. Surgery, 1990. 108: pp. 331–337 53. Hunt, T., et al., Effect of vitamin A on reversing the inhibitor effect of cortisone on healing of open wounds in animals and man. Ann Surg, 1969. 170: pp. 633–641 54. Wicke, C., et al., Effects of steroids and retinoids on wound healing. Arch Surg, 2000. 135(11): pp. 1265–1270 55. Hunt, T.K. and H.W. Hopf, Wound healing and wound infection. What surgeons and anesthesiologists can do. Surg Clin North Am, 1997. 77(3): pp. 587–606 56. Ueno, C., T.K. Hunt, and H.W. Hopf, Using physiology to improve surgical wound outcomes. Plast Reconstr Surg, 2006. 117(7 Suppl): pp. 59S–71S

Discussion Terzi: Is there any risk for patients in giving high

oxygen? Hopf: Giving patients 100% oxygen is largely risk-

free. If they are newborns, you should probably avoid 100% oxygen. So for everybody who is afraid

12

of oxygen toxicity, there is no evidence of any in the short term. Schumpelick: What about anemia and wound healing? Hopf: Anemia is good for wound healing as long as your heart works because the viscosity goes down and you get better blood flow in the wound. I have measured wound oxygen in a test group of volunteers, and there was no difference in patients without anemia, especially if you give them oxygen, because a better flow combined with a good oxygenation leads to good wound oxygen level.

13

Mesh-Related Infections After Hernia Repair M. E. Falagas, G. C. Makris

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Chapter 13 · Mesh-Related Infections After Hernia Repair

Introduction Open or laparoscopic »tension-free« mesh implantation for hernia repair of abdominal wall defects has been the gold standard treatment because it appears to reduce the rate of recurrence by an average of 30–50% in comparison with the simple nonmesh herniorrhaphy. However, the use of artificial meshes within the human body is not without potential clinical problems and might lead to various complications such as seromas (fluid accumulation), adhesions, chronic severe pain, migration or even rejection of the mesh, and, of course, mesh-related infections [1, 2]. These complications may even be life-threatening and usually necessitate hospitalization and surgical removal of the troublesome mesh. Mesh-related infections, along with seroma formation, are the most common complications encountered during ventral or inguinal hernia repair, although infection is definitely the one with the most devastating consequences for the patient. Every year almost 30,000 inguinal and just as many ventral hernia repairs become infected, both in the United States and Europe. New improved techniques and stricter aseptic protocols in the operating room have contributed to a decrease in wound infection rates after hernia repair, but this still appears to be center dependent.

13 Risk Factors The risk factors for surgical site infections (SSIs) in herniorrhaphy are gender (female > male), age over 70, comorbidities (diabetes, obesity), operating time, and the prophylactic use of drainage or prostheses. Even though artificial implants pose an independent risk factor for the development of SSIs, other factors also affect the incidence of postherniorrhaphy mesh-related infection rates [1]: ▬ Type of mesh [polyester, polypropylene (PP), or polytetrafluoroethylene (PTFE)] ▬ Type of surgical technique used to apply the mesh (laparoscopic or open) ▬ Relationship of the mesh to the peritoneum (transabdominal preperitoneal or totally extraperitoneal)

▬ Perioperative administration of prophylactic antibiotics and type of sterile techniques applied in the operating room ▬ Mesh placement in contaminated tissues ▬ Other factors, such as smoking and immunosuppression

Incidence of Mesh-Related Infections Elective primary abdominal reconstruction with mesh is considered a clean surgery, with infection rates of up to 8% being reported [1]. The rate of infection may vary among centers and appears to be influenced by underlying comorbidity (diabetes, immunosuppression, obesity) and by specific factors mentioned earlier, which will be discussed in following sections.

Operating Technique and Type of Mesh Laparoscopic hernioplasty compared with open mesh procedures has been proven to induce a lower incidence of surgical wound infections, probably due to the lack or relatively limited physical contact of the mesh with the surgical wound during the operation. However, the specific type of laparoscopic technique used (transabdominal preperitoneal versus totally extraperitoneal mesh implementation) is not associated with different rates of infections, but data are still insufficient to support this statement. The type of implemented mesh is also of vital importance regarding the development (or not) of an infection [3]. Monofilament polypropylene (PP) is the most frequently used biomaterial for repair of an abdominal wall defect due to the low infection rates compared with other nonabsorbable types of meshes. The biocompatibility and the large pore size of this PP textile permit the relatively uncompromised inflammatory response of the immune system on the surface of this material. Engelsman et al. [3] reviewed the infection rates of different kinds of nonabsorbable meshes after open repair hernioplasty and noted important variations: ▬ Polypropylene meshes: 2.5–5.9% ▬ Expanded polytetrafluoroethylene (ePTFE) meshes: 0–9.2%

99 Chapter 13 · Mesh-Related Infections After Hernia Repair

▬ Polyester meshes: most polyester infection rates are quite similar to those of polypropylene meshes, but rates of up to 16% have also been documented Surgical technique and patient and mesh characteristics are responsible for the above differences. The pathophysiologic mechanisms and certain characteristics of the meshes underlying the above differences will be discussed in a following paragraph.

Antimicrobial Prophylaxis and Preoperative Aseptic/Sterilization Protocols Preoperative administration of antimicrobial agents in clean surgical procedures such as primary hernioplasty has been a matter of considerable debate for years, but a recent meta-analysis by Sanabria et al. [4] of the accumulated evidence suggests that infection rates were decreased by almost 50% in the patients who received antimicrobial prophylaxis. Stricter operative aseptic protocols in combination with proper prophylactic antibiotic coverage was also demonstrated to be effective in further restricting surgical posthernioplasty wound infections in a large series of patients who underwent »clean« surgical repair of abdominal wall defects.

Mesh Placement in Contaminated Areas Hernia repair is considered a clean operation. Nevertheless, when bowel opening or abdominal wound infection has previously occurred, this procedure becomes contaminated; thus, the implementation of an artificial material was thought for years to be contraindicated. However, recent studies suggest that minor morbidity, minimal risk of infection, and minor wound-related mortality are observed after mesh placement in contaminated tissues. Apparently, more solid evidence is required.

13

Smoking and Other Comorbidities Smoking, prolonged operating time, and patient comorbidities such as diabetes, immunosuppression, and obesity have been incriminated for a further increase in the incidence of surgical wound infections after hernioplasty.

Microbiology and Pathophysiology of Mesh-Related Infections The isolated microflora in mesh-related infections are usually associated with Staphylococcus species, especially S. aureus; Streptococcus spp., including group B streptococci; and Gram-negative (mainly Enterobacteriaceae) and anaerobic bacteria [5]. In addition, microbiological data confirm that strains of methicillin-resistant S. aureus have been isolated in mesh-related infections after hernia repair, as have Candida spp. and Mycobacterium spp., although to a far lesser extent. Microbes have an extraordinary ability to adhere to surfaces to produce colonies and maintain their functional status. In particular, certain pathogens, including S. aureus, may adhere even to artificial surfaces such as metal and cause implant-related infections. Bacteria may adhere to inanimate surfaces, produce slime (which causes stronger and irreversible adhesion), and form biofilms, which have the ability to communicate through quorum sensing and resist internal mechanisms of defense. In addition, they build tight junctions with the underlying biomaterial, creating complex, large structures that are not easily ingested by phagocytes. Highly porous material with a large surface area and numerous niches–such as the multifilament meshes–provides pathogens with an excellent environment protected from the immune system of the host. Niches function as a shelter for the pathogens’ colonies because of the large size of phagocytes. Niches are small in diameter, but at the same time, they substantially increase the total area of the mesh, raising the possibility for successful bacterial adherence [6]. Porous materials are connected with higher infection rates because they downsize the normal inflammatory response of the infected host organism.

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Chapter 13 · Mesh-Related Infections After Hernia Repair

Finally, the hydrophobic or hydrophilic properties of implanted materials also influence the adhering pattern of bacteria upon them, since they determine protein absorption from the surface of the biomaterial. In vitro studies have shown that more hydrophobic materials, such as PTFE and ePTFE, may be associated with the development of more resistant forms of biofilms [6]. The above results may explain previous clinical findings that infections related to multifilament, hydrophobic ePTFE and PTFE meshes are expected to have the worst prognosis and demand surgical management.

Clinical Manifestation and Diagnosis The manifestations of mesh-related infections can be divided into surgical (superficial) wound infections and deep-seated mesh infections and may occur 2 weeks to 39 months from the day of mesh implantation.

Surgical Wound Infections

13

Surgical wound infections are the most commonly encountered type of infection, presenting at an early postoperative stage, usually days or a few weeks after the mesh placement. The symptoms and signs are typical of local acute inflammation: pain, erythema, swelling with locally increased temperature, and confined tenderness. Inappropriate treatment of surgical wound infections may be complicated by the formation of a discharging fistula, intraabdominal abscess, or, rarely, osteomyelitis. The emergence of systemic symptoms such as fever, chills, or rigor and malaise should urge prompt investigation and initiation of therapeutic actions before sepsis occurs.

Deep-Seated Mesh Infections Deep-seated mesh infections generally manifest in the early postoperative period, but infrequently they can also be observed as a late-onset phenomenon that is delayed for months or years (up to 4.5 years after the operation) [7]. Deep-seated in-

fections may result from persistent fluid collection (seromas) leading to chronic groin sepsis. Symptoms can be chronic, recurrent, or totally absent until the progression to sepsis.

Diagnosis The combination of clinical presentation, physical examination, laboratory values, and previous medical history is usually adequate to establish a diagnosis. However, when there are doubts regarding differential diagnosis, two noninvasive imaging techniques could provide physicians with a solution: Bedside ultrasound and computerized tomography may reveal the inflammatory process in the adipose tissue around the implant because of the different ultrasonic and density characteristics, respectively. Complications such as the presence of fistula or abscess could also be depicted. Diagnostic paracentesis of mesh-associated seromas when there are no signs of inflammation should be carefully considered and not performed routinely; there is a high risk of transforming a potentially aseptic reaction to an infectious process through the introduction of bacteria into the previously aseptic seromas.

Treatment and Antimicrobial Prophylaxis Therapeutic Options: Surgical or Conservative The therapeutic options available following the development of mesh-related infection can be separated according to the type and severity of infection and the type of implanted mesh. ▬ Posthernioplasty superficial wound infections may have a better prognosis and may be treated conservatively using proper intravenous antimicrobial coverage and drainage when signs of accumulated exudate exist. However, the use of drainage is still controversial due to insufficient evidence. ▬ In limited, deep-seated infections of the mesh, prolonged antibiotic treatment in combination with percutaneous or open drainage has

101 Chapter 13 · Mesh-Related Infections After Hernia Repair

been reported to be effective to restrain the infectious process. However, when extensive infection is present–due to biofilm formation and limited penetration of the drug in the area–mesh removal and surgical cleaning of the wound pose the best possible treatment to eradicate the infection. Unfortunately, the labeling of a mesh-related infection as limited or extensive remains empirical. Hernia recurrence could be a postoperative complication if adequate fibrous tissue had not developed earlier (early-onset, deep-seated infections). ▬ The choice between conservative and surgical treatment could also be influenced by the type of implanted mesh. Structural (monofilament or multifilament) and biochemical (hydrophobic or hydrophilic) properties influence the potential response of the infection to the administered antibiotics. Clinical findings in combination with recent in vitro experiments suggest that infected hydrophobic meshes– such as PTFE and ePTFE–are most likely to be removed in order to achieve complete cure. So far, no universal recommendations based on randomized controlled trials exist for the optimal treatment of mesh-related infections. Further data

13

are warranted to establish evidence-based algorithms for treating infections according to the type and severity of infection and the type of mesh.

Prophylaxis Due to the special features of implant devices, the best way to treat an implant-related infection without destroying the implant is to take the appropriate measures to avoid initial exposure to infectious agents. Considerable effort has been made to develop techniques that will restrain the fundamental mechanisms for implant-related infections, which are bacterial adhesion and colonization of artificial surfaces and biofilm formation. Various strategies such as antimicrobial prophylaxis and mesh coatings of antimicrobial biomaterials have been developed, but so far, comparative data are lacking. Preoperative antimicrobial prophylaxis in elective, »clean« surgical procedures such as repair of an abdominal wall defect with a mesh has been a matter of considerable controversy for years. Nevertheless, recent meta-analysis of accumulated data provides evidence of significantly lower SSI rates after proper prophylaxis. The antimicrobial

Hospital surgical site infection rate

Low (<1%)

High (>1%)

Assess individual risk factors

Preoperative prophylaxis

High-risk patient

Preoperative prophylaxis

Low-risk patient

No preoperative prophylaxis

⊡ Fig. 13.1. Proposed algorithm for preoperative antimicrobial prophylaxis

102

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Chapter 13 · Mesh-Related Infections After Hernia Repair

agents most commonly used are cefazolin 1–2 g (or 1 g erythromycin if the patient is allergic), 1.5 g ampicillin/sulbactam , 2 g amoxicillin/clavulanic acid, or 1.5 g cefuroxime. Unfortunately, there are still no data regarding the cost-effectiveness of this approach. Infection rates can be center dependant and can be as low as 1% in some cases. Therefore, researchers have suggested that institutions revise their SSI rates and decide, according to each patient’s special risk factors, whether antimicrobial prophylaxis is justified. (See ⊡ Fig. 13.1). Mesh coating with antimicrobial agents or other biomaterials that decrease the adhesion ability of bacteria, increase host tissue ingrowth, or initiate bacterial destruction have been developed to prevent implant colonization and biofilm formation in the first place. Apart from antibiotic coatings (such as cefoxitin), silver, gold, titanium carbonitride, polyglactin, gelatin, and other biomaterials have been used as coatings, with different mechanisms of action. At present, however, evidence is based on experimental and animal studies, and the available comparative data are insufficient to draw safe conclusions Universal recommendations regarding the choice of mesh type or the best possible antimicrobial prophylaxis cannot be supplied based on the available evidence from randomized controlled trials [8]. Until further trials are completed to shed more light on these controversial issues, the choice of mesh and antibiotic coverage will be center dependent and, in particular, derived from the surgeon’s experience and the financial cost.

References 1.

2.

3.

4.

Falagas ME, Kasiakou SK. Mesh-related infections after hernia repair surgery. Clin Microbiol Infect 2005; 1:3–8 Bliziotis IA, Kasiakou SK, Kapaskelis AM, Falagas ME. Meshrelated infection after hernia repair: case report of an emerging type of foreign-body related infection Infection 2006; 1:46–48 Engelsman AF, van der Mei HC, Ploeg RJ, Busscher HJ. The phenomenon of infection with abdominal wall reconstruction. Biomaterials 2007; 14:2314–2327 Sanabria A, Domínguez LC, Valdivieso E, Gómez G. Prophylactic antibiotics for mesh inguinal hernioplasty: a meta-analysis. Ann Surg 2007; 3:392–396

5.

6.

7.

8.

Falagas ME, Velakoulis S, Iavazzo C, Athanasiou S. Meshrelated infections after pelvic organ prolapse repair surgery. Eur J Obstet Gynecol Reprod Biol 2007; 2:147–156 Engelsman AF, van der Mei HC, Busscher HJ, Ploeg RJ. Morphological aspects of surgical meshes as a risk factor for bacterial colonization. Br J Surg 2008; 8:1051–1059 Delikoukos S, Tzovaras G, Liakou P, Mantzos F, Hatzitheofilou C. Late-onset deep mesh infection after inguinal hernia repair. Hernia 2007; 1:15–17 Eriksen JR, Gögenur I, Rosenberg J. Choice of mesh for laparoscopic ventral hernia repair. Hernia 2007; 6:481–492

Discussion Heniford: When I talk to our patients about lap-

aroscopic versus open ventral hernia repair, the number one reason to recommend laparoscopic repair is not pain, and it is not cosmetics—it’s a decreased risk of infection, by far. When we look back at our patients and compare the different risk factors for infection, the number one reason is smoking.

14

Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field J. J. Diaz

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Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field

Introduction Repair of a ventral hernia is one of the most common surgical procedures performed in the United States. Yet ventral hernia repair in the setting of a contaminated surgical field presents a very difficult surgical dilemma. Prosthetic mesh has been widely employed since the 1950s for the elective repair of ventral hernias. Beyond hernia recurrence, prosthetic mesh has known complications such as infection, contracture, and intestinal fistula formation. In the setting of a clean-contaminated and/or dirty surgical field, prosthetic mesh is contraindicated due to high complication rates [1–4]. The alternative, closing of a ventral hernia with an absorbable mesh, presents its own set of problems. Repair with absorbable mesh only serves to keep the patient from evisceration. It is a temporizing procedure for a planned ventral hernia repair, and it continues to be associated with a high rate of wound infection that is unaffected by the use of an absorbable mesh [5–7].

Patient Population

14

Patients with complex hernias remain a very difficult group to repair. Complex hernias are commonly described as follows: open abdomen after trauma/emergency; general surgery resulting in a planned ventral hernia; presence of an intestinal fistula, ostomy, or infected mesh. Patients who have a history of multiple hernia repairs, loss of domain, or loss of abdominal tissue and musculature are also labeled as having complex hernias. Patients with a previous history of infected mesh or wound infection have a high risk of developing another surgical site infection [8, 9]. In all of these cases, the use of prosthetic mesh would be considered a contraindication in hernia repair. To date, no classification system is universally accepted for defining ventral hernias. A ventral hernia can range from a simple periumbilical hernia in a patient with no comorbidities to an abdominal catastrophe with a planned ventral hernia, a split-thickness skin graft over the viscera, and an atmospheric fistula. Manufacturers have started to develop biological mesh with the intent to produce a product that

can become vascularized and resist infection. In addition, the ideal product must have the tensile strength of native fascia or be comparable to prosthetic mesh, be pliable, and be easy to implant. To date, only human acellular dermal matrix has demonstrated its ability to resist infection. The development of human acellular dermis (HADM) as a fascial graph replacement presents a potential alternative to hernia closure in a compromised surgical field. HADM is derived from human donors (LifeCell, Branchburg, NJ, USA). The donated human skin is supplied by the American Association of Tissue Banks and is approved by the U.S. Food and Drug Administration as banked human tissue. Under a proprietary process, HADM is cleansed of any immune reactive cells or cellular components. HADM is being used to reduce complications seen with prosthetic mesh, such as infection, adhesions, fistulas, seromas, bleeding, and skin erosion [10, 11].

Repair Types The most common ventral hernia repair types mesh to »bridge« the defect using a tension-free repair. A prosthetic mesh with 3–4 cm of overlap of the fascial edge has been used as an onlay or sublay [12, 13]. Interposition mesh placement is well known to have the highest recurrence rate and is not a recommended surgical technique. Luijendijk et al., in the only randomized controlled trial of mesh vs. primary suture repair, showed that the rate of hernia recurrence could be reduced by using a prosthetic mesh [12]. We hypothesized that a human acellular dermal matrix would be a suitable biological tissue alternative for repairing ventral hernia in the presence of a contaminated surgical field by better tolerance to wound infection, thereby reducing the incidence of prosthesis removal.

Methods We performed a retrospective study of a single institution’s experience with HADM (⊡ Fig. 14.1). Patients were admitted from January 2001 to

105 Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair

14

All study patients N=75

Clean-contaminated N=64

Contaminated or dirty N=11

SSI

Yes N=21

Medically managed N=9

SSI

No N=43

Surgically managed N=12

Yes N=4

No N=7

Medically managed N=2

Surgically managed N=2

Mesh removed =4

December 2004 to Vanderbilt University Medical Center and included surgical cases from the trauma, general surgery, and emergency general surgery services. Before the study began, approval was granted by the Vanderbilt University Institutional Review Board.

Study Population Patients were included if they were greater than 15 years of age and had undergone repair of a ventral hernia or traumatic anterior wall fascial defect with acellular human dermis (AHD) in a compromised surgical field. Surgical involvement of the following organ systems was required for inclusion: stomach, small bowel, colon, appendix, hepatobiliary system, urinary bladder, spleen, and ostomy formation. This also included removal of infected mesh or repair of an enterocutane-

Mesh removed =1

⊡ Fig. 14.1. Study design (SSI surgical site infection)

ous fistula. The medical center’s electronic data repository (StarPanel) and hospital administrative database were used to accurately collect patient data. Demographic data collected (⊡ Table 14.1) included age, gender, race, hospital length of stay, and comorbidities, which in turn included diabetes mellitus, hypertension, renal insufficiency (serum creatine <30 mg/h), chronic obstructive pulmonary disease, heart disease, and hepatic disease (cirrhosis). The wound classification was recorded for each patient. The Centers for Disease Control and Prevention (CDC) wound classification system was used to define surgical wounds [10] (⊡ Table 14.2). The operative technique for each hernia repair was also recorded (⊡ Table 14.3). The type of suture used for each AHD repair (absorbable vs. permanent) was also recorded in the database. The study population was divided into two groups: cleancontaminated (CC) and contaminated/dirty (CD).

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Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field

⊡ Table 14.1. Study demographics

⊡ Table 14.2. Wound classification

n

Wound classification

Wound criteria

Clean

Elective, not emergency, nontraumatic; primarily closed; no acute inflammation; no break in technique; respiratory, gastrointestinal, biliary, and genitourinary tracts not entered

Clean-contaminated

Urgent or emergency case that is otherwise clean; elective opening of respiratory, gastrointestinal, biliary, or genitourinary tract with minimal spillage (e.g., appendectomy); no encountering of infected urine or bile; minor technique break

Contaminated

Nonpurulent inflammation; gross spillage from gastrointestinal tract; entry into biliary or genitourinary tract in the presence of infected bile or urine; major break in technique; penetrating trauma <4 h old; chronic open wounds to be grafted or covered

Dirty

Purulent inflammation (e.g., abscess); preoperative perforation of respiratory, gastrointestinal, biliary, or genitourinary tract; penetrating trauma >4 h old

75 Value

% / SD

51.5

14.5

Male

36

48.0

Female

39

52.0

Age Gender

Race (%) White

60

80.0

Black

11

14.7

Other

5

6.7

Cardiac

15

20.0

Hypertension

34

45.3

Diabetes mellitus

23

30.7

Renal

4

5.3

Chronic obstructive pulmonary disease

5

6.7

Hepatic

3

4.0

Chronic steroids

4

5.3

Length of stay

16.7

20.8

Charges

$158,183

$206,896

Died (sepsis)

1

1.3

⊡ Table 14.3. Operative repair type

Home

56

74.7

Repair type

Repair description

Transfer /rehabilitation

18

24.0

Inlay (sublay)

Reinforcing sheet of acellular human dermis is positioned deep to the anterior abdominal wall defect

Onlay

Reinforcing sheet of acellular human dermis is positioned superficial to the defect

Component separation

Releasing incisions are made in the external oblique muscle with rectus reinforcement with acellular human dermis

Interposition

The edges of the acellular human dermis graft are sutured directly to the edges of the fascial defect

Comorbidity (%)

Hospital

Disposition (%)

14

Outcomes The primary outcome measured in this study was the incidence of surgical site infection (SSI) as per the CDC definitions for nosocomial infections. Management of the wound infection was divided into medical management (intravenous antibiotic only) and surgical management (operative incision and drainage plus intravenous antibiotics). Also recorded was whether the AHD was removed.

14

107 Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair

Secondary variables included early hernia recurrence (<1 year); septic complications, including ventilator-associated pneumonia; urinary tract infection; and blood stream infection.

Statistics Statistical analysis was performed using chi-square tests to evaluate statistical significances between patient subgroups.

Results Seventy-five patients met the study criteria. The overall wound infection rate was 33.3%: 11 medically managed infections (14.7%) and 14 surgically managed infections (18.7%). The average length of hospital stay was 16.7 days (+20.8) with a mean follow-up of 275 (+209) days. With respect to the entire patient population, 25 out of 75 patients (33.3%) developed an SSI, and 12 patients had hernia recurrence (16%). The CC group (n=64) had nine wound infections that

were medically managed (14.1%) and 12 wound infections that were surgically managed (18.8%). The CD group (n=11) had two wound infections that were medically managed (18.2%) and two that were surgically managed (18.2%). Five of 14 surgically managed (35.7%) wound infections required removal of the mesh.

Subgroup Analysis The patient population was divided into two subgroups based on wound type: clean-contaminated (CC) and contaminated or dirty (CD). Sixty-four patients had CC wounds, and 11 patients had CD wounds (⊡ Table 14.4). Within the CC group, there were 21 SSI: 9/64 patients (14.1%) were medically managed, and 12/64 patients (18.8%) were surgically managed. Of the 12 surgically managed wound infections, five necessitated removal of the HADM (33.3%) either because of enterocutaneous fistula formation (n=4) or HADM infection (n=1; see ⊡ Table 14.5). Within the follow-up period (average 269 days), a total of 12 patients (16%) in the CC group experienced hernia recurrence.

⊡ Table 14.4. Clean-contaminated (CC) and contaminated/dirty (CD) subgroup analysis (HR hernia recurrence; LOS length of stay; WC wound closure during initial procedure; FUD follow-up days Groups

n

HR (%)

LOS (SD)

WC (%)

FD (SD)

Clean-contaminated

64

10

15.6

15.4

19.6

64

100

269

186

Contaminated/dirty

11

2

18.2

24.3

27.7

8

72.7

306

277

Total

75

12

16.0

19.8

23.6

72

96

275

201

⊡ Table 14.5. Inpatient infection rate (MM medical management; SM surgical management) n (%)

Inpatient Total (%)

MM (%)

SM (%)

Clean-contaminateda

64

85.3

21

32.8

9

14.1

12

18.8

Contaminated/dirty

11

14.7

4

36.4

2

18.2

2

18.2

Totals

75

100

25

33.3

11

14.7

14

18.7

aMesh

removal in five patients

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Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field

Surgical Technique and Suture Analysis Outcomes were also evaluated with respect to the type of hernia repair implemented (⊡ Table 14.6). The ventral hernia repair type with the lowest occurrence of wound infection was the onlay technique (n=15), with 6.7% of patients developing an SSI. This was followed by inlay (n=27; 33.3%), interposition (n=23; 43.5%), and component separation (n=10; 50%). The repair method most successful at preventing hernia recurrence was the inlay method, with only 7.4% of patients developing a secondary hernia. This was followed by component separation (10%), onlay (13.3%), and interposition (30.4%). Although general trends in differences in wound infection and hernia recurrence rates are evident, none of these differences was statistically significant. Patients were also stratified by the type of suture used for the procedure, and outcomes were determined. Thirty-one percent (31.3%) of the patients who were repaired with absorbable sutures (n=32) developed a postoperative SSI, and 25% experienced hernia recurrence. Patients repaired with permanent sutures (n=38) had a slightly higher SSI rate at 34.2%, but a lower rate of her-

nia recurrence, at 10.5%. Again, the differences between infection and recurrence rates were not statistically significant. It should be noted that the type of suture used in five patients was unknown, and two developed a surgical wound infection (⊡ Table 14.7). It was concluded that wound infection in the contaminated surgical field occurred 33.3% of the time; 18.7% of the cases required surgical management, and 35.7% of these required removal of the HADM.

Discussion Because of the high rates of infection, hernia recurrence, and the occasional need for mesh removal with synthetic hernia repair in a contaminated surgical field, surgeons continue to search for other methods and materials to manage this difficult dilemma [15, 16]. One such material that has garnered attention is HADM. Studies have demonstrated that acellular grafts such as HADM have shown reduced postsurgical inflammation and rapid cellular infiltration and revascularization [17, 18]. This has been attributable to the

⊡ Table 14.6. Surgical repair technique and outcomes (WI wound infection; MM medical management; SM surgical management; HR hernia recurrence)

14

Repair type

n

WI (%)

MM (%)

SM (%)

HR (%)

Inlay

27

9

33.3

5

55.6

4

44.4

2

7.4

Onlay

15

1

6.7

1

6.7

0

0.0

2

13.3

Interpositional

23

10

43.5

3

30.0

7

70.0

7

30.4

Component separation

10

5

60.0

2

30

3

30.0

1

20.0

⊡ Table 14.7. Suture type and outcomes (WI wound infection; MM medical management; SM surgical management; HR hernia recurrence) Suture typea

n

WI (%)

Absorbable (PDS)

32

10

31.3

7

70.0

3

30.0

8

25.0

Permanent (Prolene)

38

13

34.2

4

30.8

9

69.2

4

10.5

aSuture

type unknown in five cases

MM (%)

SM (%)

HR (%)

109 Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair

macroarchitecture of the HADM, which is native human dermis. The HADM is a three-dimensional implant of tissue with an intact basement membrane, collagen fibers, elastin filaments, hyaluronan, and proteoglycans, as well as patent capillary network channels [19]. Once HADM is vascularized, the very nature of its structure allows it to resist infection when implanted into the anterior abdominal wall. Animal models have also shown that HADM offers the same tensile strength as synthetic materials, while achieving superior revascularization [20]. Our study substantiates the increasing amount of evidence demonstrating the utility of HADM in ventral hernia repairs, especially in a compromised surgical field. It is generally accepted that synthetic prostheses are contraindicated in a compromised surgical field because of unacceptably high rates of infection and hernia recurrence. However, no prospective trials have evaluated outcomes between HADM and synthetic mesh repairs. Our results and those of others suggest that ventral hernias repaired with HADM have acceptably low rates of infection and hernia recurrence compared with those repaired with nonbiological prostheses. Voyles et al. reported nine polypropylene mesh removals out of 29 (31%) surgically contaminated ventral hernia repairs due to infection or fistula formation [21]. Animal models have also shown high rates of polypropylene and polytetrafluoroethylene mesh removal due to infection [22, 23]. Geisler et al. reported hernia recurrence of 43% with synthetic mesh in compromised surgical fields [24]. The overall rates of wound infection (33.3%) and hernia recurrence (16%) in this study are consistent with studies reporting complication rates for synthetic prostheses in compromised surgical fields. Several previous studies also evaluated outcomes in hernia repair using HADM and demonstrated lower complication rates as well. Buinewicz and Rosen, in a retrospective review of 44 patients who underwent incisional hernia repair or TRAM flap surgery using HADM, reported a 7% postoperative wound infection rate and 5% hernia recurrence in clean surgical fields. No patient required reoperation or removal of the HADM [10]. Kolker et al. reported no hernia recurrences and only two

14

seromas from a pool of 16 ventral hernia patients in clean surgical settings [25]. Butler et al. evaluated the effectiveness of HADM in 13 suboptimal surgical patients in whom polypropylene mesh was contraindicated (perioperative radiation, placement of mesh directly over the bowel with bacterial contamination) [26]. Only two seromas (15%), one hematoma (8%), one occurrence of partial flap necrosis (8%), one case of enterocutaneous fistula formation (8%), and one case of wound dehiscence (8%) were noted. This study demonstrates the usefulness of HADM in compromised surgical fields. Scott et al. have also explored the application of HADM for open abdominal wound closure [27]. HADM was used to definitively close 37 open abdomens that would not have otherwise closed primarily. The results were favorable: two SSIs (5.4%), one intraabdominal abscess (2.7%), and no hernia recurrences. A prosthetic mesh infection is a complex surgical problem. In most cases, this progresses to a chronic septic state, which usually mandates removal of the mesh. Under these circumstances, immediate repair requires either autologous tissue material or a staged surgical repair. Yet these cases have a universally high wound infection rate. In our study, we had a 33% wound infection rate, but only five cases required removal of the AHD during the early experience. The revascularization of the HADM coupled with early surgical management of complex surgical wound infections allowed us to salvage the repair. It became clear that a surgical wound infection did not always equal a mesh infection. The impact of hernia repair type on patient outcomes demonstrates general agreement with the existing literature. Several studies have shown that the interposition technique yields the highest frequency of complications, whereas the inlay approach involves complications least frequently [28, 29]. Although no particular method was statistically superior in our small patient population, the numbers strongly discourage the use of interpositional hernia repair. The existing literature also favors inlay (sublay) repair, but in our study, the onlay technique proved to be less prone to infection and just as resistant to hernia recurrence as the inlay technique. Component separation repairs

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Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair in the Compromised Surgical Field

also had a low rate of recurrence (10%) but a much higher rate of wound infection (50%). Again, the size of our patient population did not allow for statistical significance, but the results favor either inlay or onlay HADM placement. Repair of these complex ventral defects with onlay, inlay, or component separation surgical techniques commonly requires large adjacent skin flaps. This allows for mobilization of the skin and primary closure of the surgical wound. This technique results in large subcutaneous spaces that are commonly managed with drains to allow egress of collected fluid, with collapse of the space. In our study, drains were universally used for this purpose. White et al. [9] found that abnormal fluid collections are the most frequent problem in these types of hernia repairs. However, the use of drains does not reduce the incidence of complications such as wound infection or seroma formation.

Strengths and Limitations

14

This is the largest study to date using AHD in a compromised surgical field, and it was conducted at a large academic referral center. This is a retrospective review, with all the limitations and problems associated with such a study. We did not have a control arm, and the follow-up period was extremely limited. This was a heterogeneous population that included trauma, general surgery, and emergency general surgery cases. As such, no long-term analysis or conclusions can be gathered from the data. Future studies are required to directly compare the use of acellular human dermis vs. prosthetic mesh regarding the long-term success of ventral repair in a prospective fashion.

Conclusion Our analysis demonstrates the value of AHD for repairing a ventral hernia in a compromised surgical field. The relatively low rate of surgical wound infection and hernia recurrence coupled with the infrequent necessity for AHD removal favors its use over synthetic mesh for contaminated ventral hernia closure [30].

References 1. Trupka AW, Schweiberer L, Hallfeldt K, Waldner H. Management of large abdominal wall hernias with foreign implant materials (Gore-tex patch). Zentralbl Chir 1997;122:879–884 2. Bleichrodt RP, Simmermacher RKJ, Van der Lei B, Schakenraad JM. Expanded polytetrafluoroethylene patch versus polypropylene mesh for the repair of contaminated defects of the abdominal wall. Surg Gyn Obst 1993;176: 18–24 3. Voyles CR,Richardson JD, Bland KI, et al. Emergency abdominal wall reconstruction with polypropylene mesh. Short term benefits versus long term complications. Ann Surg 1981; 194:219–223 4. Temudom T, Siadati M, Sarr JG. Repair of complex giant or recurrent ventral hernias by using tension-free intraparietal prosthetic mesh (Stoppa technique): lessons learned from our initial experience (fifty patients). Surgery 1996; 120:738–744 5. Finan KR, Vick CC, Kiefe CI, Neumayer L, Hawn MT. Predictors of wound infection in ventral hernia repair. Am J Surg 2005;190(5):676–681 6. Scott BG, Feanny MA, Hirschberg A. Early definitive closure of the open abdomen: a quiet revolution. Scand J Surg 2005;94(1):9–14 7. Mayberry JC, Burgess EA, Goldman RK, et al. Enterocutaneous fistula and ventral hernia after absorbable mesh prosthesis closure for trauma: the plain truth. J Trauma 2004;57(1):157–162 8. Houck JP, Rypins EB, Sarfeh IJ, et al. Repair of incisional hernia. Surg Gynecol Obst 1989; 169:397–399 9. White TJ, Santos MC, Thompson JS. Factors affecting wound complications in repair of ventral hernias. Am Surg 1998;64(3):276–280 10. Buinewicz B, Rosen B. Acellular cadaveric dermis (acellular human dermis): a new alternative for abdominal hernia repair. Ann Plast Surg 2004; 52:188 11. Bauer JJ, Harris MT, Kreel I, et al. Twelve-year experience with expanded polytetrafluoroethylene in the repair of abdominal wall defects. Mt Sinai J Med 1999; 66: 20–25 12. Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 2000; 343(6):392–398 13. Burger JW, Luijendijk RW, Hop WC, et al. Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 2004; 240(4):578–583 14. The Hospital Infection Control Practices Advisory Committee. Guidelines for prevention of surgical site infection. Am J Infect Control 1999; 27:109–110 15. Diaz JJ Jr, Gray BW, Dobson JM, et al. Repair of giant abdominal hernias: does the type of prosthesis matter? Am Surg 2004;70(5):396–401; discussion 401–402 16. Leber GE, Garb JL, Alexander AI, Reed WP. Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 1998;133(4):378–382

111 Chapter 14 · Human Acellular Dermal Matrix for Ventral Hernia Repair

17. Livesey SA, Herndon DN, Hollyoak MA, et al. Transplanted acellular allograft dermal matrix. Potential as a template for the reconstruction of viable dermis. Transplantation 1995;60(1):1–9 18. Eppley BL. Experimental assessment of the revascularization of acellular human dermis for soft-tissue augmentation. Plast Reconstr Surg 2000; 107:757 19. LifeCell. AlloDerm Regenerative Tissue Matrix. http:// www.lifecell.com/products/95/ 20. Silverman RP, Singh NK, Li EN, et al. Restoring abdominal wall integrity in contaminated tissue-deficient wounds using autologous fascia grafts. Plast Reconstr Surg 2004;113(2):673–675 21. Voyles CR, Richardson JD, Bland KI, et al. Emergency abdominal wall reconstruction with polypropylene mesh: short-term benefits versus long-term complications. Ann Surg 1981;194(2):219–223 22. Bleichrodt RP, Simmermacher RKJ, van der Lei B, et al. Expanded polytetra-fluoroethylene patch versus polypropylene mesh for the repair for contaminated defects of the abdominal wall. Surg Gynecol Obstet 1993; 176:18 23. Brown GL, Richardson JD, Malangoni MA, et al. Comparison of prosthetic materials for abdominal wall reconstruction in the presence of contamination and infection. Ann Surg 1985; 201:705 24. Geisler DJ, Reilly JC, Vaughan SG, Glennon EJ, Kondylis PD. Safety and outcome of use of nonabsorbable mesh for repair of fascial defect in the presence of open bowel. Dis Colon Rectum 2003; 46(8):1118–1123 25. Kolker AR, Brown DJ, Redstone JS, Scarpinato VM, Wallack MK. Multilayer reconstruction of abdominal wall defects with acellular dermal allograft (acellular human dermis) and component separation. Ann Plast Surg 2005;55(1):36–41; discussion 41–42 26. Butler CE, Langstein HN, Kronowitz SJ. Pelvic, abdominal and chest wall reconstruction with acellular human dermis in patients at increased risk for mesh-related complications. Plast Reconstr Surg. 2005;116(5):1263–1275; discussion 1276–1277 27. Scott BG, Scott BG, Welsh FJ, et al. Early aggressive closure of the open abdomen–a new approach. J Trauma 2006;60(1):17–22 28. Ueno T, Pickett LC, de la Fuente SG, et al. Clinical application of porcine small intestinal submucosa in the management of infected or potentially contaminated abdominal defects. J Gastrointest Surg 2004;8:109–112 29. de Vries Reilingh TS, van Geldere D, et al. Repair of large midline incisional hernias with polypropylene mesh: comparison of three operative techniques. Hernia 2004;8(1):56–59 30. Langer C, Liersch T, Kley C, Flosman M, et al. Twenty-five years of experience in incisional hernia surgery. A comparative retrospective study of 432 incisional hernia repairs. Chirurg 2003;74(7):638–645

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15

Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh A. S. Fawole, R. P. C. Chaparala, N. S. Ambrose

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Chapter 15 · Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh

Introduction

15

Over 70,000 groin hernias are repaired each year in England and Wales. Tension-free mesh hernioplasty is a commonly performed procedure for repair of inguinal hernias. It is relatively easy to perform, with one of the lowest recurrence rates of the available repairs [1], and studies have shown that this is a safe procedure with very few complications [2]. But there are concerns about infection because of the introduction of a foreign material into the body. Surgical site infection following inguinal hernia repair has been reported to be anything from 0 to 15%. The majority of these are superficial infections and do not appear to be influenced by the presence of a mesh [3]. These usually settle spontaneously with the use of antibiotics and sometimes require superficial incision and drainage. However, deep wound infection is a serious complication leading to chronic groin sepsis, which requires removal of the prosthetic mesh material to allow resolution of the infective process. Taylor and O’Dwyer [4] identified 12 cases of chronic groin sepsis following mesh repair of an inguinal hernia in Scotland over a 4-year period, all of which required complete or partial removal of the mesh to resolve the sepsis. Follow-up data were available for 11 of these 12 patients, two of whom developed hernia recurrence following mesh removal, although the duration of follow-up was not stated for the rest of the patients. One of these patients, who developed a recurrence about 2 years after initial mesh removal, had a further mesh repair that, unfortunately, once again led to groin sepsis requiring removal of the second mesh to control the infection. The other patient remained asymptomatic on follow-up, and the recurrence was thus not treated surgically [4]. Case reports have not observed hernia recurrence following removal of infected mesh material inserted by the open [5] or laparoscopic [6] techniques. A randomised controlled trial of prophylactic antibiotics in mesh hernioplasties found four cases of deep infection in the overall population of 280 patients studied (1.4%). Three of these required mesh removal for symptom control, and all three had no evidence of hernia recurrence at 1 year follow-up [7].

The aim of this study was to determine the incidence of inguinal hernia recurrence following the removal of an infected prosthetic mesh. In addition, the perioperative complications and long-term symptoms associated with removal were reviewed.

Patients and Methods Over an 8-year period from January 1, 1995, to December 31, 2002, 2,017 patients [1,892 male, 125 female; median age 60 (range 15–95) years] had repair of inguinal hernias in our university teaching hospital. Of these, 122 patients had bilateral hernias repaired, making a total of 2,139 inguinal hernias repaired in this study period; 1,955 were primary inguinal hernias, and 184 procedures were performed for a recurrent inguinal hernia. A retrospective case note review of patients who had mesh removal after inguinal hernia repair was undertaken. These notes were retrieved from records obtained from the operating theatre database system, which searched for all patients who had mesh removal. All patients with groin sepsis requiring mesh removal were included; however, two patients had removal of mesh for chronic groin pain and were excluded. Patients were further followed up by a telephone interview and were subsequently reviewed in the surgical outpatient clinic by one of the authors (NSA) to determine the outcomes after mesh removal. The main outcome measures were incidence of hernia recurrence and chronic groin pain.

Results Fourteen patients [11 male, three female; median age 60 (range 24–77) years] had mesh removal for chronic groin sepsis during this 8-year period. Only one of these patients had repair of a recurrent inguinal hernia as the initial procedure; all the others had repair of primary inguinal hernias. One patient had repair of bilateral primary inguinal hernias, but there was evidence of infection on one side, which resulted in removal of the mesh. An onlay polypropylene mesh was used in all of

115 Chapter 15 · Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh

the patients except one, who had only a polypropylene mesh plug repair. The mesh was secured with staples in five patients, and a polypropylene suture was used in the remaining nine, including the patient who had a mesh plug repair. Seven of these 14 patients had their initial hernioplasty performed as a day-case procedure. Six patients had a planned overnight stay. One patient had a delayed discharge (9 days) because of a scrotal haematoma that was treated conservatively. Six of the 14 patients received a dose of prophylactic antibiotic at the time of their operation (Table 15.1). There was no evidence of infection at the time of discharge in any of these patients. Two patients developed deep wound infection at 1 month. Another four were routinely seen at about 2 months, and none of them had evidence of infection at that time. The remaining eight patients did not have a routine postoperative clinic

15

appointment and were seen only after developing deep infection. Infection was first noticed in the groin at a mean of 11 (range 1–35) months following hernia repair (⊡ Table 15.1). There is no statistical difference between the mean times to first presentation of those patients who had prophylactic antibiotics (10 months) and those who did not (12.5 months); p=0.33. All patients were initially treated conservatively with repeated courses of antibiotics for a mean period of 10 (range 1–49) months. Mesh removals were performed at a mean of 22 (range 2–62) months following the initial hernia repair. All mesh removals were performed under general anaesthetic, and there were no perioperative complications. Eight patients had specimens sent for bacteriology at the time of operation, and six of these grew Staphylococcus aureus on culture.

⊡ Table 15.1. Use of prophylactic antibiotics, period of conservative management, and timing of operation in patients who had mesh removal Patient

Prophylactic antibiotics

Duration between initial operation and first sign of infection (months)

Period of conservative management with antibiotics (months)

Duration between initial operation and mesh removal (months)

1

Yes

1

4

5

2

None documented

3

3

6

3

None documented

28

1

29

4

Yes

13

49

62

5

None documented

35

9

44

6

None documented

9

25

36

7

None documented

7

1

8

8

None documented

4

26

30

9

Yes

8

3

11

10

None documented

13

4

17

11

Yes

7

10

17

12

Yes

25

4

29

13

Yes

6

6

12

14

None documented

1

1

2

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Chapter 15 · Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh

All the patients who had mesh removal were followed up. After a median period of 44 (range 5–91) months, there were two recurrences, which were both asymptomatic. One of these patients noticed a lump in the groin 5 months following mesh removal, but this was asymptomatic, and he elected to have this treated conservatively. He was reviewed 10 months following recurrence and has remained asymptomatic. The other patient had a persistent minor groin discharge after mesh removal, which settled completely after 2 months. He was reviewed in the clinic 41 months after mesh removal and had remained asymptomatic, but clinical examination revealed a cough impulse suggestive of a small recurrent hernia. On questioning, none of the patients complained of pain or discomfort that interfered with their usual level of activity.

Discussion

15

Chronic groin sepsis is a dreaded complication of inguinal hernia repair using prosthetic material. Intuitively, prophylactic antibiotics would appear to be indicated in hernia repair with mesh, as this procedure involves introducing a foreign body into the groin. However, the literature is certainly divided regarding the use of prophylactic antibiotics in mesh repair of inguinal hernias. A Cochrane review of the literature [8] was unable to conclude a benefit for recommending antibiotic prophylaxis in elective primary inguinal hernia repair. A subsequent update in 2007 came to the same conclusion but suggested that antibiotics could not be argued against when high infection rates are detected. In this present series, the use of prophylactic antibiotics was documented in six out of 14 patients and did not appear to confer a benefit in preventing mesh infection. Deep infection tends to present after a delayed period following mesh repair of inguinal hernias; there was a mean period of 10 months’ delay in this group of patients. Use of prophylactic antibiotics does not appear to alter the time to presentation with deep infection (p=0.33). Available reports suggest that deep wound infection is uncommon following mesh repair of in-

guinal hernias [2, 4, 7], but it does usually require removal of the mesh to facilitate cessation of the groin sepsis [4, 5, 9]. We have shown a deep infection rate of about 0.7% (14 out of 2,017 patients). This is higher than in some reports, 0.03% [2], but is comparable to other studies that found deep infection rates of 1.4% [7] and even higher rates of superficial infection [10]. A wide range of surgeons with no particular interest in hernia repair, including mostly surgical trainees, performed the operations in this present study. This heterogeneous group of operating surgeons may partly explain the relatively higher rate of deep infections compared with specialist hernia repair centres. Inexperienced surgeons may excessively handle the mesh, which may contribute to development of deep infection. Although contamination at the time of operation is the likely source of infection in superficial infections, this is unlikely to be the aetiology in deep infections, which often present after a delayed period. These may be a result of haematogenous spread from distant sites [4]. It has been suggested that conservative treatment of groin infections with antibiotics leads to resolution of infection [11]. This is a reasonable proposition when there is only superficial infection of the subcutaneous tissue, but deep infection persists until there is surgical extirpation of the infected prosthetic material. In our series, groin sepsis did not settle even with repeated prolonged courses of antibiotics in some of the patients. Removal of infected prosthetic mesh is potentially associated with operative complications because of the concomitant inflammatory reaction that may make tissue planes more difficult to find. Meticulous surgical technique is thus necessary to ensure careful dissection and prevent intraoperative damage to structures, especially within the spermatic cord. In this study, no complications were associated with mesh removal. All mesh removals were performed by a consultant surgeon or a senior surgical trainee under the direct supervision of the consultant. For most of the patients (12 out of 14), there were no attempts to reinforce the transversalis fascia, which was thickened and fibrosed even after mesh removal. Two patients

117 Chapter 15 · Fate of the Inguinal Hernia Following Removal of Infected Prosthetic Mesh

had loose plication of the fascia with interrupted absorbable polydioxanone sutures. After a median follow-up period of 44 (5–91) months, only two of the 14 patients who had mesh removal for deep infection had developed hernia recurrence. These cases remained asymptomatic and were thus treated conservatively. Deep-seated wound infection has also been reported following laparoscopic hernia repair and also requires removal of the mesh, which can be done laparoscopically or by an open technique. Even after laparoscopic surgery, mesh removal does not appear to lead to hernia recurrence [6]. In conclusion, deep-seated wound infection following inguinal hernia repair is uncommon. When it does occur, it results in chronic groin sepsis, which in the majority of cases requires removal of the infected material before symptoms resolve. However, hernia recurrence is not inevitable, suggesting that the strength of a mesh repair lies in the fibrous reaction evoked within the transversalis fascia by the prosthetic material rather than in the physical presence of the mesh itself. With careful dissection, an infected mesh can be removed without any associated complications. Therefore, in established deep infection, physicians should not hesitate to remove an infected mesh to allow resolution of chronic groin sepsis. Patients should be warned that they may develop a recurrence. We would advise repairing this by a posterior (laparoscopic) approach after removal of mesh following an anterior (open) mesh hernioplasty.

References 1. Lichtenstein IL, Shulman AG, Amid PK, Montllor MM. (1989) The tension-free hernioplasty. Am J Surg 157:188– 193 2. Shulman AG, Amid PK, Lichtenstein IL. (1992) The safety of mesh repair for primary inguinal hernias: results of 3,019 operations from five diverse surgical sources. Am Surg 58:255–257 3. Mann DV, Prout J, Havranek E, Gould S, Darzi A. (1998) Late-onset deep prosthetic infection following mesh repair of inguinal hernia. Am J Surg 176:12–14 4. Taylor SG, O’Dwyer PJ. (1999) Chronic groin sepsis following tension-free inguinal hernioplasty. Br J Surg 86:562– 565

15

5. Ismail W, Agrawal A, Zia MI. (2002) Fate of chronically infected onlay mesh in groin wound. Hernia 6:79–81 6. Avtan L, Avci C, Bulut T, Fourtanier G. (1997) Mesh infections after laparoscopic inguinal hernia repair. Surg Laparosc Endosc 7:192–195 7. Yerdel MA, Akin EB, Dolalan S, Turkcapar AG, Pehlivan M, Gecim IE, Kuterdem E. (2001) Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial. Ann Surg 233:26–33 8. Sanchez-Manuel FJ, Seco-Gil JL. (2003) Antibiotic prophylaxis for hernia repair. Cochrane Database Syst Rev:CD003769 9. Hatada T, Ishii H, Ichii S, Ashida H, Yamamura T. (2000) Late infection after mesh-plug inguinal hernioplasty. Am J Surg 179:76–77 10. Taylor EW, Duffy K, Lee K, Hill R, Noone A, Macintyre I, King PM, O’Dwyer PJ. (2004) Surgical site infection after groin hernia repair. Br J Surg 91:105–111 11. Gilbert AI, Felton LL. (1993) Infection in inguinal hernia repair considering biomaterials and antibiotics. Surg Gynecol Obstet 177:126–130

Discussion Jacob: Concerning infection after groin hernia

repair, have you looked at those patients who have a local anesthetic compared to those who have general anesthesia? Fawole: We haven’t looked at this special point. But you are right; there might be a risk for bringing bacteria into the tissue during the local anesthesia.

16

Mesh Infection–Therapeutic Options E. Schippers

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Chapter 16 · Mesh Infection–Therapeutic Options

Introduction The use of meshes in hernia repair has become standard procedure throughout the world. Implantation of a mesh has been found to reduce the rate of recurrence in the repair of incisional hernias [1–3]. However, mesh-related complications have become increasingly important. Postherniorrhaphy mesh infection, mesh bowel intrusion, fistula formation, and eventual removal and reinsertion have been induced by mesh contamination during primary surgery. Mesh-related infections following surgery occur relatively infrequently compared with other device-related infections; an incidence of mesh-related infections after incisional hernia repair up to 8% has been reported [4]. The relevance of bacterial contamination is controversial in the literature, although it is of considerable clinical importance to the patient and surgeon. Deysine describes mesh infection with consecutive migration and fistula formation as a catastrophe [5]. In vascular surgery, even more dramatic consequences of infected prostheses, including a mortality rate of 75%, were reported in earlier times. Patients with an infected prosthesis would ultimately die from massive hemorrhage or septicemia unless the prosthesis was removed [6]. However, in renal transplant recipients with immunosuppression and comorbidities such as obesity, diabetes, and chronic pulmonary diseases, surgical repair of infected or contaminated herniation with polypropylene mesh is safe and effective and yields excellent results [7].

16

Type of Mesh Shortly after introducing polyethylene mesh for replacing tissue defects, Usher [8] underscored the relevance of mechanical and biological properties of the mesh that are associated with the type of tissue structure. In experiments with infected wounds in dogs, he demonstrated that knitted material and taffeta weave were equally inert to infection. He attributed this in part to the use of a monofilament and to the structure of the knit-

ted fabric, which consists of a series of loops with no interlocking knots that might harbor serum and bacteria. With increasing recognition of the value of biomaterials for the repair of abdominal wall hernias, knowledge of biomaterial-related complications required in-depth knowledge and understanding of the physical properties of the prostheses. Consequently, Amid [9] proposed a classification of available biomaterials for hernia surgery based on their pore size: Type I: Totally macroporous prostheses containing pores larger than 75 μm, a pore size that is required for admission of macrophages, fibroblasts, blood vessels, and collagen fibers into the pores Type II: Totally microporous prostheses; these prostheses contain pores that are less than 10 μm in at least one of their three dimensions Type III: Macroporous prostheses with multifilamentous or microporous components, braided polypropylene mesh, or braided Dacron mesh Surgical infection promoted by implantation of biomaterials is caused by infection and proliferation of bacteria into and within the pores and interstices of these synthetic materials. When pores are less than 10 μm, bacteria averaging 1 μm cannot be eliminated by macrophages and neutrophilic granulocytes, which are too large to enter a 10-μm three- dimensional pore. Type I prostheses deter housing and growth of bacteria by allowing macrophages, rapid fibroplasia, and angiogenesis, which also prevents infiltration and growth of bacteria. Types II and III prostheses are similar to braided suture materials, and by harboring bacteria, they can promote their growth, likewise resulting in biomaterial-related infection. With respect to this classification and to the biomaterial-related complications, Amid concluded that in cases of infection, the totally macroporous prostheses (type I) do not have to be removed. To manage the infection, drainage and local wound care are all that is necessary. In cases of infection with type II or III mesh, total removal (II) or partial removal of type III is required. Leber et al. [10] analyzed the long-term complications associated with prosthetic repair of incisional hernia. They found that late infections appearing months or even years after surgery were

121 Chapter 16 · Mesh Infection–Therapeutic Options

more challenging. These were often combined with complex fistulas involving bowel, and the mesh had to be removed. In their study, multifilamented polyester mesh was associated with a significantly greater number of infections. Based on this clinical observation, the influence of the presence of either a monofilament or multifilament mesh material on the bacterial infection risk was studied in a rat model [11]. The extent of adherent bacteria corresponded to the estimated filament surface, thus favoring the use of monofilament materials. Robinson et al. reviewed medical device reports from the U.S. Food and Drug Administration on the use of surgical mesh for hernia repair. The analysis of 252 reports revealed a percentage of 42% related to infection. Polytetrafluoroethylene (PTFE) mesh especially tended to be associated with more infections. Another conclusion was that cases of polypropylene infections can be healed without mandatory removal of the mesh [12].

Role of Bacteria Deysine [13] categorized meshes into two groups: those that are hydrophobic, such as expanded PTFE, and those that are hydrophobic, including polyester and polypropylene. Those repelling water take more time to become integrated by the fibroblastic response. Likewise, hydrophobic materials may initially repel the fluids containing bacteria. The role of bacteria in cases of rejection was described as follows: Prostheses are rejected through the process of suppuration after becoming colonized by bacteria [5]. In order to adhere, bacteria undergo functional changes such as the production of slime, which enhances an irreversible and strong adhesion. Slime production is a major pathogenic property of bacterial strains that form biofilms on surfaces. Once the microorganisms have adhered to a biomaterial’s surface, they are protected against phagocytosis because the microorganisms and biomaterials together are too large to ingest. Although a variety of different bacteria can cause a prosthetic infection, the usual causative organ-

16

isms associated with cases of mesh infections are Staphylococcus spp., especially Staphylococcus aureus; Streptococcus spp.; gram-negative bacteria (mainly Enterobacteriaceae); and anaerobic bacteria [14]. The reported high rate of 63% of methicillin-resistant Staphylococcus aureus (MRSA) complicating intraperitoneal mesh implantation is alarming [4].

Diagnosis Patients usually present with symptoms and signs of local acute inflammation: pain, erythema, increased temperature, and tenderness and swelling in the abdominal wall in the area of the mesh. Systemic manifestations include fever, malaise, and chills or rigor. Abdominal abscesses and discharging fistulas can be the first clinical manifestation. To monitor prosthetic infections, erythrocyte sedimentation rate (ESR), C-reactive protein, and white blood cell count are well-established laboratory methods. White blood cell counts have a sensitivity of only 20% and a predictive value of 50%. The combination of ESR and C-reactive protein is a more powerful diagnostic tool; when both are negative, the possibility of infection is zero. When both are positive, the possibility of infection is 83% [15].

Imaging With the help of ultrasound, a noninvasive procedure, most mesh-related complications can be detected or ruled out. An abscess formation is seen as a hypoechogenic structure caused by cell debris, with small plump hyperechoic reflections caused by gas bubbles. The extent of incomplete fistulas within the abdominal wall can be determined. The hypoechoic structure of the fistula channel can be followed through the abdominal wall (⊡ Fig. 16.1). Computed tomography and magnetic resonance imaging allow clear identification of abdominal wall pathologies. Indications for these are sonographically uncertain results; however, the disadvantages include higher costs, limited availability, and the danger of contrast medium allergy. Fistu-

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Chapter 16 · Mesh Infection–Therapeutic Options

Antibiotics

⊡ Fig. 16.1. Typical sonographic finding of an abscess formation and fistula channel with hypoechoic structures

lography reveals the extent, location, and relation of fistulas and is therefore a helpful tool in preoperative planning.

Treatment

16

Therapeutic options in cases of mesh infection range from prevention and intravenous antibiotics to open wound treatment and mesh removal. The essential factor in the evolution and persistence of infection is the formation of a biofilm around the implanted device [16]. The biofilm is capable of resisting antimicrobial agents due to the protective mechanism. Adequate prevention of a biomaterial-centered infection is therefore aimed at the first contact of a microorganism with a biomaterial. Bacterial adhesions on the biomaterial depend on the material surface. Mesh coated with different precious metals, such as titanium, silver, or gold, can successfully reduce bacterial attachment [17]. Because ultrasound reduces biofilm formation, several studies on the effect of ultrasound on bacterial cell growth and on the treatment of biomaterial-centered infections have been performed. A positive effect of ultrasound in addition to treatment with antibiotics has been shown. Theoretically, a phenomenon called the bioacoustic effect enhances the transportation and penetration of antibiotics within the biofilms. The contribution of low-frequency and high-intensity ultrasound in the presence of an antibiotic agent removes and kills microorganisms [18].

Bacterial susceptibility to pharmacological treatment is significantly reduced when a polymeric device is present. Possible reasons for the reduced susceptibility of biofilm-embedded organisms to antibiotic agents include a slow rate of bacterial growth within the biofilm, inhibition of antimicrobial activity by biofilm substances, and poor penetration of the biofilm by antibiotics [19]. Therefore, the strategy of monotherapy with intravenous antibiotics in cases of mesh-related infections has a poor outcome and consequently has no indication [14].

Open Wound Treatment Standard surgical practice supports removing prosthetic material when a wound infection involves the prosthesis. The removal of mesh in this situation is often technically difficult and may result in substantial additional complications. Local tissue incorporation can make removal of mesh dangerous because adjacent vascular structures or the bowel can be injured, which may result in acute bleeding or subsequent development of an enterocutaneous fistula. Because achieving closure of the fascial defect after mesh removal is usually not possible, this surgery may result in an incisional hernia that is larger than the original one. In early postoperative infections after implantation of porous mesh, it is therefore advised to introduce an open wound management strategy combined with a suction-based debridement system as an alternative to explantation of the mesh. The principle of vacuum sealing has been introduced for the treatment of complicated wounds [20]. The first step is wound opening, followed by necrosectomy, wound debridement, and irrigation. A polyvinyl vacuum foam is cut to size and placed into the wound. A vacuum-assisted closure system with transparent polyurethane foil is applied to the open portion of the wound and skin (⊡ Fig. 16.2). Permanent suction at 60–80 kPa must be established. The foam is removed at 2–5-day intervals, with the transparent foil allowing daily inspection of the wound. This treatment results in progressive

123 Chapter 16 · Mesh Infection–Therapeutic Options

16

a

⊡ Fig. 16.3. Example of a microporous mesh followed by late infection and fistula that had to be removed

b ⊡ Fig. 16.2. Steps in vacuum sealing after early mesh infection. a Cutting the foam to size. b Vacuum-assisted closure system in place

debridement and granulation of the open wound and causes a dermatotraction with approximation of the wound edges. After successful wound conditioning, a secondary closure of skin over the mesh can be achieved without mesh removal. However, mesh explantation is recommended for all type II prostheses (totally microporous) [9]. Furthermore, later infections after months or even years are more challenging and also require removal of the prosthesis [21]. They are often combined with complex fistulas involving the bowel. In these cases, preservation of the mesh is likely to fail, and sooner or later the mesh has to be removed [22] (⊡ Fig. 16.3).

Conclusion Mesh infection is a serious, but not catastrophic, complication in hernia surgery. The extent of the damage correlates with the type of mesh that was

primarily implanted. With respect to prevention and therapy, the ideal mesh is macroporous, hydrophilic, and monofilamented. Two-thirds of infections are caused by Staphylococcus spp., and methicillin-resistant staphylococci are frequent. The therapeutic options are both mesh-related and time-related. Open wound treatment, including vacuum sealing, is indicated in early postoperative infection of macroporous meshes. Explantation should be limited to microporous meshes or late and chronic infections, which are often complicated by sinus or fistula formation. Monotherapy with antibiotics should be abandoned. Interesting aspects for future research in this field include biofilm formation, bioacoustic effects, and mesh coatings.

References 1. Luijendijk RW, Hop WC, van den Tol MP, et al. (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–398 2. Schumpelick V, Klosterhalfen B, Müller M, et al. (1999) Minimierte Polypropylen Netze zur präperitonealen Netzplastik (PNP): eine prospektive randomisierte klinische Studie. Chirurg 70:422–430 3. Schippers E, Harsányi A, Thumbs A, Schneider M (2001) Ergebnisse nach offener Netzplastik der Narbenhernie in Sublay-Technik. Viszeralchirurgie 36:152–156 4. Copp WS IV, Harris JB, Lokey JS, McGill ES, Klove KL (2003) Incisional herniorrhaphy with intraperitoneal composite mesh: a report of 95 cases. In: Proceedings of the Sou-

124

5.

6.

7.

8.

9.

10.

11.

12.

13. 14.

15.

16.

16

17.

18.

19. 20.

21.

Chapter 16 · Mesh Infection–Therapeutic Options

theastern Surgical Congress, 7–11 February 2003, Savannah, Georgia. Vol 69, pp. 784–787 Deysine M (2004) The catastrophe: mesh infection and migration with fistula formation–life-long risk? In: Schumpelick V, Neuhaus LM (eds) Meshes: benefits and risks. Springer, Berlin, pp 207–227 Fry WJ, Lindenauer SM, Arbor A (1967) Infection complicating the use of plastic arterial implants. Arch Surg 94:600–609 Antonopoulos IM, Nahas WC, Mazzucchi E, Piovesan AC, Birolini C, Lucon AM (2005) Is polypropylene mesh safe and effective for repairing infected incisional hernia in renal transplant recipients? Urology 66:874–877 Usher FC (1961) Knitted Marlex mesh: an improved marlex prosthesis for repairing hernias and other tissue defects. Arch Surg 82:153–155 Amid PK (1997) Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia 1:15–21 Leber GE, Garb JL, Alexander AI, Reed WP (1998) Longterm complications associated with prosthetic repar of incisional hernias. Arch Surg 133:378–382 Klinge U, Junge K, Spellerberg B, Piroth C, Klosterhalfen B, Schumpelick V (2002) Do multifilament alloplastic meshes increase the infection rate? Analyses of the polymeric surface, the bacteria adherence and the in vivo consequences in a rat model. J Biomed Materials Res 63:765–771 Robinson TN, Clarke JH, Schoen J, Walsh MD (2005) Major mesh-related complications following hernia repair: events reported to the Food and Drug Administration. Surg Endosc 19:1556–1560 Deysine M (1998) Management of prosthetic infections in hernia surgery. Surg Clin North Am 78:1105–1115 Falagas A, Kasiakou SK (2004) Mesh-related infections after hernia repair surgery. European Society of Clinical Microbiology and Infectious Diseases, CMI, 11:3–8 Salvati EA, Callaghan JJ, Brause BD, et al. (1986) Reimplantation in infection. Elution of gentamicin from cement and beads. Clin Orthop Rel Res 207:83–93 Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science; 284:1318–1322 Engelsmann AF, van der Mei HC, Ploeg RJ, Busscher HJ (2007) The phenomenon of infection with abdominal wall reconstruction. Biomaterials 28:2314–2327 Johnson LL, Peterson RV, Pitt WG (1998) Treatment of bacterial biofilms on polymeric biomaterials using antibiotics and ultrasound. J Biomater Sci Polym Ed 9:1177– 1185 Darouiche R (2004) Treatment of infections associated with surgical implants. N Engl J Med 350:1422–1429 Fleischmann W, Bacher U, Bischoff M, Hoekstra H (1995) Vacuum sealing: indication, technique and results. Eur J Orthop Surg Traumatol 5:37–40 Flament JB, Avisse C, Palot JP, Delattre JF (1999) Biomaterials–principles of implantation. In: Schumpelick V, Kings-

north AN, et al. (eds) Incisional hernia. Springer, Berlin, pp 217–227 22. Klinge U, Conze J, Krones CJ, Schumpelick V (2005) Incisional hernia: open techniques. World J Surg 29:1066–1072

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Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery? T. J. Aufenacker

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Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery?

Introduction

17

A mesh-based repair is, in many Western countries, the most popular technique for repairing abdominal wall hernia in order to reduce the risk of recurrence [1–7]. More than 80% of adult abdominal wall hernias occur in the groin, and in the Western world the majority are being repaired with the use of a prosthetic mesh. There is a large variation in techniques used to correct a groin hernia, with an even larger variety of meshes. Currently the most popular inguinal hernia technique is the Lichtenstein hernia repair [8], using a flat mesh to reinforce the inguinal wall. The incidence of infection after inguinal hernia repair has been reported to vary from 0% to 9% [9]. Especially when a foreign body, such as a polypropylene mesh, is used, prevention of a deep infection is of paramount importance because a deep infection of a mesh may require its removal, as reported in several cases [10]. A Cochrane Review meta-analysis for inguinal hernia [11] in 2004 concluded that »antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded« because the number of included patients was limited and that »further studies are needed, particularly on the use of mesh repair.« Although most studies, as discussed later in this chapter, do not support the use of antibiotic prophylaxis, its use is still widespread. The reason for this might be legislative in many cases since an American attorney, for instance, could ask a so-called expert during a court of law about a lack of antibiotic prophylaxis. In some cases, this expert might well be a psychiatrist without updated knowledge in this area, and his or her advice would be misleading to those hearing the case. Many American surgeons admit to continuing to use antibiotic prophylaxis for this reason. Both in the United States and Europe, over 1.5 million abdominal wall hernia repairs (of which 70% are groin hernia repairs) are performed annually [12]. Therefore, any improvement in their treatment could have a large medical and economic impact. A reduction in the number of wound infections would especially have a great effect on patient satisfaction, sick leave, and wound

care. Conversely, discarding the use of antibiotic prophylaxis in hernia repair could reduce costs, the risks of toxic and allergic side effects, and the possible development of bacterial resistance [13] or superinfections. To assess whether systemic antibiotic prophylaxis prevents wound infection in groin hernia repair, a systematic review and a meta-analysis of randomised controlled trials were carried out.

Material and Methods A search of Medline, EMBASE, CINAHL, DARE, ACP, LILACS, and the Cochrane Register using the terms hernia and antibiotic prophylaxis was done to identify randomised controlled trials on the subject published between 1966 and May 2008. All languages were considered. The search was performed independently by two reviewers, who selected potentially relevant papers based on title and abstract. References from the selected papers were used for search completion. Field experts were contacted for potential data, and books of the abstracts from leading hernia meetings over the last 8 years were manually checked for unpublished data. All randomised placebocontrolled trials using antibiotic prophylaxis in mesh abdominal wall hernia repair with explicit defined wound infection criteria and a minimum follow-up period of 1 month were included. Each paper was reviewed independently by three reviewers, and a quality assessment was performed according to the scoring system of Jadad et al. [14]. Discrepancies among the reviewers were resolved by consensus. Only papers with a Jadad score ≥3 were considered appropriate for further analysis. Data were extracted from the studies and pooled using the Review Manager software [15] from the Cochrane Collaboration. A χ2 test for heterogeneity of study results was performed. If heterogeneity could not be detected, data were pooled using a random effects model to correct for clinical diversity and methodological variations between studies. The effectiveness of antibiotic prophylaxis to prevent wound infection was expressed as odds ratios (ORs) for dichotomous

127 Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection

data and their 95% confidence intervals (CIs). Numbers needed to treat (NNT) and 95% CIs were calculated from the OR and the background risk of wound infection for the patients in the placebo groups. No subgroup analysis was performed. If it remained unclear from a study whether data were presented for patients or hernias, a sensitivity analysis (worst-case scenario) was done by varying the distribution of bilateral hernia between the treated and placebo groups.

Results The search resulted in a large number of potentially relevant studies, identifying nine papers reporting prospective randomised data on the use of antibiotic prophylaxis in groin hernia surgery with prosthetic reinforcement. After the Cochrane meta-analysis update in 2007, no additional trials in the area of nonmesh repairs were published. In this Cochrane analysis, one study combining three trials with unpublished data is included. Therefore, the data regarding nonmesh techniques from the Cochrane meta-analysis

17

(⊡ Table 17.1) are used to perform an analysis with the random-effect model. A nonsignificant effect of antibiotic prophylaxis in nonmesh techniques was demonstrated, OR 0.75 (0.53–1.06), NNT 85 (45–359). Regarding the mesh-based techniques, a summary of the nine papers that included randomised trials and the outcome of the assessment is given in ⊡ Table 17.2. The results of the three assessments did not differ among the three reviewers. The only laparoscopic study, by Schwetling and Barlehner [16], used an incorrect randomisation method and lacked a definition of wound infection, but in the absence of more studies on this technique, it was considered best evidence. Eight studies were, after the quality assessment, suited for meta-analysis regarding the use of antibiotic prophylaxis in mesh-based repairs. They included 2,963 open inguinal and 43 femoral hernia repairs. The patient and surgical characteristics of these eight randomised controlled trials are documented in ⊡ Table 17.3. The included studies are presented separately with their main intervention and results in ⊡ Table 17.4.

⊡ Table 17.1. Pooled data of six studies on the use of antibiotic prophylaxis for prevention of wound infection after nonmesh inguinal hernia repair Review: The effectiveness of antibiotic prophylaxis in inguinal hernia repair Comparison: 01 Antibiotic prophylaxis vs: placebo Outcome: 03 Non mesh techniques Study or sub-category

Antibiotic n/N

Placebo n/N

Evans

1/48

2/49

Anderson

5/137

Platt

OR (random) 95% Cl

Year

2.01

0.50 [0.04, 5.70]

1973

6/150

8.14

0.91 [0.27, 3.05]

1980

4/301

6/311

7.33

0.68 [0.19, 2.45]

1990

Lazorthes

0/155

7/153

1.45

0.06 [0.00, 1.11]

1992

Taylor

25/283

25/280

35.35

0.99 [0.55, 1.77]

1997

Pessaux

68/2008

20/394

45.72

0.66 [0.39, 1.09]

2006

Total (95% Cl)

2932

1337

100.00

0.75 [0.53, 1.06]

Total events: 103 (Antibiotic), 66 (Placebo) Test for heterogeneity: Chi2= 4.31, df = 5 (P= 0.51), I2 = 0% Test of overall effect: Z= 1.63 (P=0.10)

OR (random) 95% Cl

0.1 0.2 0.5 1 2 5 10 Favours treatment Favours control

Weight %

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Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery?

⊡ Table 17.2. Results and quality of prospective randomised studies on the use of antibiotic prophylaxis in the prevention of wound infection after mesh groin hernia repair Reference

Jadad score

Number of patients

Infection %

Correct randomisation?

Doubleblind?

Wound infection definition?

Follow-up period?

Accepted in metaanalysis?

Laparoscopic inguinal hernia mesh repair (transabdominal preperitoneal) Schwetling [16] 1998

0

80

0.0%

No, alternately

No

No definition

Unknown

No; best evidence

Open inguinal and femoral hernia mesh repair

17

Morales [17] 2000

4

524

1.9%

Yes

Yes

Yes

1 year

Yes

Yerdel [18] 2001

5

269

4.8%

Yes

Yes

CDC criteria [25]

1 year

Yes

Celdran [19] 2004

4

91

4.4 %

Yes

Yes

CDC criteria [25]

2 years

Yes

Oteiza [20] 2004

3

247

0.4%

Yes

No

CDC criteria [25]

1 month

Yes

Aufenacker [21] 2004

5

1,008

1.7 %

Yes

Yes

CDC criteria [25]

3 months

Yes

Perez [22] 2005

5

360

3.1%

Yes

Yes

CDC criteria [25]

1 month

Yes

Tovaras23 2007

5

379

3,7%

Yes

Yes

Yes

1 month

Yes

Jain24 2008

5

120

1.7%

Yes

Yes

CDC criteria25

1 month

Yes

The total number of infections after groin hernia repair with a mesh-based technique was 48/1,526 patients (3.1%) in the placebo group and 24/1,480 patients (1.6%) in the antibiotic group. The pooled data for the eight studies are presented in ⊡ Table 17.5. There was no statistical heterogeneity (p=0.36). The OR for wound infection after antibiotic prophylaxis was 0.59 (95% CI 0.34–1.03), resulting in an NNT of 80 (49–1111). A sensitivity analysis was performed because the Celdran study [19] did not specify in which group the eight bilateral hernias were included (worst-case scenario: infection rate in Celdran’s placebo group 4/41=9.8%), resulting in an OR of 0.57 (95% CI 0.32–1.04). The number of deep infections after inguinal and femoral hernia repair was 6/1,050 in the placebo group (0.6%) and 3/1,053 in the antibiotic

prophylaxis group (0.3%), with an OR of 0.50 (95% CI 0.12–2.09) and an NNT of 352 (199–1961). The pooled data of six studies (the Morales and Tzovaras data were not available) are presented in ⊡ Table 17.6.

Discussion In this systematic review and meta-analysis on the effectiveness of antibiotic prophylaxis in groin hernia repair, the six randomised controlled trials concerning non-mesh-based techniques and the nine mesh-based trials demonstrate no significant benefit of antibiotic prophylaxis. For groin hernias, the wound infection rate reported in randomised controlled trials of 2.4% after

17

129 Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection

⊡ Table 17.3. Patient and study characteristics of eight randomised controlled trials on antibiotic prophylaxis in inguinal and femoral hernia mesh repair (PHS Prolene Hernia System) Morales [17] N=524a

Yerdel [18] N=269a

Celdran [19] N=99b

Oteiza [20] N=247a

Aufenacker [21] N=1,008a

Perez [22] N=360a

Tzovaras [23] N=379a

Jain [24] N=120a

Total infections (%)

1.9%

4.8%

4.4%

0.4%

1.7%

3.1%

3.7%

1.7%

Deep infection (%)

0.8%

1.5%

0%

0%

0.3%

0.6%

Not documented

0%

Mesh removal (%)

0.8%

1.1%

0%

0%

0.2%

0.6%

0%

0%

Body mass index (mean)

Not documented

25.0

26.2

Not documented

Not documented

Not documented

26.0

Not documented

Diabetes

Not documented

Study exclusion criterion

18 (18.1%)

Not documented

Study exclusion criterion

Not documented

13 (3.4%)

Study exclusion criterion

Recurrent hernia

39 (7.4%)

Study exclusion criterion

13 (13.1%)

Study exclusion criterion

Study exclusion criterion

Study exclusion criterion

Not documented

Study exclusion criterion

Duration of surgery

34 min

63 min

65 min

40 min

40 min

53 min

45 min

58 min

Surgeons (%) Residents (%)

524 (100%) 0 (0%)

0 (0%) 269 (100%)

75 (75.8%) 24 (24.2%)

247 (100%) 0 (0%)

571 (56.6%) 437 (43.4%)

Not documented

Not documented

120 (100%) 0 (0%)

Bilateral hernia

0 (0%)

0 (0%)

8 (8.8%)

Study exclusion criterion

56 (5.6%)

Study exclusion criterion

Study exclusion criterion

Study exclusion criterion

Femoral hernia

23 (4.4%)

Study exclusion criterion

Study exclusion criterion

20 (8.1%)

Study exclusion criterion

Study exclusion criterion

Study exclusion criterion

Study exclusion criterion

Use of drains

Study exclusion criterion

60 (22.3%)

Not documented

Not documented

15 (1.5%)

0 (0%)

15 (4.0%)

0 (0%)

Local anaesthetics

Not documented

111 (41.3%)

99 (100%)

226 (91.5%)

17 (1.7%)

0 (0%)

329 (86.8%)

Not documented

Day surgery

51 (9.7%)

Not documented

99 (100%)

247 (100%)

463 (45.9%)

Not documented

Not documented

0 (0%)

Mesh type

Flat, polypropylene

Flat, polypropylene

Flat, polypropylene

Flat, polypropylene

Flat, polypropylene

Flat, polypropylene

Flat, polypropylene

PHS, polypropylene

Exclusion bias [26]

30/554 (5.4)

11/280 (3.9%)

0/91 (0%)

3/250 (1.2%)

7/1,015 (0.7%)

0/360 (0%)

2/381 (0.5%)

0/120 (0%)

aN= bN=

number of patients number of hernias (91 patients)

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Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery?

⊡ Table 17.4. Results of individual studies accepted in the systematic review on the use of antibiotic prophylaxis for preventing wound infection after mesh groin hernia repair (NNT number needed to treat) Reference

N

Mean age (years)

Males (%)

Type of antibiotic

Infection placebo group (patients, %)

p-value

NNT

0%

1.0

∞

Infection intervention group (patients, %)

Laparoscopic inguinal hernia mesh repair (transabdominal preperitoneal) Schwetling [16]

80

55

86

Cefuroxime 1.5 g

0/40

0%

0/40

Open inguinal and femoral hernia mesh repair Morales [17]

524

54

90

Cefazolin 2g

6/287

2.1%

4/237

1.7%

0.737

248

Yerdel [18]

269

56

93

Ampicillin + sulbactam 1.5 g

12/133

9.0%

1/136

0.7%

0.002

13

Celdran [19]

91

58

90

Cefazolin 1g

4/49a

8.2%

0/50a

0.0%

0.059

13

Oteiza [20]

247

57

85

Amoxicillin + clavulanic acid 2 g

0/123

0.0%

1/124

0.8%

0.318

NNH 124

Aufenacker [21]

1,008

58

96

Cefuroxime 1.5 g

9/505

1.8%

8/503

1.6%

0.813

520

Perez [22]

360

61

98

Cefazolin 1g

7/180

3.9%

4/180

2.2%

0.540

59

Tzovaras [23]

379

63

94

Amoxicillin + clavulanic acid 1.2 g

9/189

4.7%

5/190

2.6%

0.4

48

Jain [24]

120

41

100

Amoxicillin + clavulanic acid 1.2 g

1/60

1.7%

1/60

1.7%

0.500

∞

aNumber

17

of hernias (91 patients)

mesh repair is not higher than the percentage after conventional sutured repair [11] (4.0%). Because the use of antibiotics is not likely to increase the wound infection percentage, the net effect of studies designed as those that were included will almost always be zero or will be in favour of the patients’ receiving prophylaxis and therefore on the left (antibiotic-favouring) side of the forest plot. The meta-analysis of six nonmesh studies demonstrated a nonsignificant effect of antibiotic prophylaxis: OR 0.75 (0.53–1.06), NNT 85 (45–359). The meta-analysis of eight studies on the use of antibiotic prophylaxis to prevent wound infection

after mesh groin hernia repair did not favour the use of antibiotic prophylaxis: OR 0.59 (95% CI 0.34– 1.03) and NNT 80 (49–1,111). In the meta-analysis, only one study of below-average size demonstrated a large and significant benefit for the prophylaxis group, but this study can be criticised because of repeated aspiration of seromas and excessive use of drains that could cause (secondary) infections; also, it is likely that the study was underpowered because it was, unfortunately, prematurely stopped because of the high rate of wound infection. However, there can be a debate about the method used for meta-analysis in this chapter be-

17

131 Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection

⊡ Table 17.5. Pooled data of eight studies on the use of antibiotic prophylaxis for preventing wound infection after mesh inguinal hernia repair Review: The effectiveness of antibiotic prophylaxis in inguinal hernia repair Comparison: 01 Antibiotic prophylaxis vs placebo Outcome: 01 Total number of wound infections Study or sub-category

Antibiotic n/N

Placebo n/N

Morales

4/237

6/287

Yerdel

1/136

Aufenacker

OR (random) 95% Cl

Year

16.78

0.80 [0.22, 2.88]

2000

12/133

7.02

0.07 [0.01, 0.58]

2001

8/503

9/505

27.05

0.89 [0.34, 2.33]

2004

Celdran

0/50

4/49

3.51

0.10 [0.01, 1.91]

2004

Oteiza

1/124

0/123

2.97

3.00 [0.12, 74.36]

2004

Perez

4/180

7/180

17.51

0.56 [0.16, 1.95]

2005

Tzovaras

5/190

9/189

21.27

0.54 [0.18, 1.64]

2007

Jain

1/60

1/60

3.89

1.00 [0.06, 16.37]

2008

Total (95% Cl)

1480

1526

100.00

Total events: 24 (Antibiotic), 48 (Placebo) Test for heterogeneity: Chi2 = 7.70, df = 7 (P = 0.36), I2 = 9.1% Test for overall effect: Z = 1.86 (P = 0.06)

OR (random) 95% Cl

Weight %

0.59 [0.34, 1.03]

0.01 0.1 1 10 100 Favours treatment Favours control

⊡ Table 17.6. Pooled data of six studies (Morales and Tsovaras data not available) on the use of antibiotic prophylaxis for preventing deep wound infection after mesh groin hernia repair Review: The effectiveness of antibiotic prophylaxis in inguinal hernia repair Comparison: 01 Antibiotic prophylaxis vs placebo Outcome: 02 Deep infections Study or sub-category

Antibiotic n/N

Placebo n/N

Yerdel

1/136

3/133

Aufenacker

1/503

2/505

Celdran

0/50

Oteiza

OR (random) 95% Cl

Year

38.96

0.32 [0.03, 3.13]

2001

34.98

0.50 [0.05, 5.54]

2004

0/49

Not estimable

2004

0/124

0/123

Not estimable

2004

Perez

1/180

1/180

1.00 [0.06, 16.11]

2005

Jain

0/60

0/60

Not estimable

2008

Total (95% Cl)

1053

1050

Total events: 3 (Antibiotic), 6 (Placebo) Test for heterogeneity: Chi2 = 0.39, df = 2 (P = 0.82), I2 = 0% Test for overall effect: Z = 0.94 (P = 0.35)

OR (random) 95% Cl

Weight %

26.12

100.00 0.01 0.1 1 10 100 Favours treatment Favours control

0.50 [0.12, 2.09]

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Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection After Groin Hernia Surgery?

cause meta-analysis is a nonperfect technique that is no substitute for a large and well-designed randomised controlled study. Nonetheless, the technique is indicated for similar situations in which the number of patients in the studies is low or when results are conflicting, as it provides pooled estimates with narrower CIs and greater statistical power. But the interpretation of a meta-analysis, especially which method to use, is essential. The choice of method should be based on the presence or absence of statistical heterogeneity within the data together with the clinical diversity and methodological diversity of the original studies. In the presence of statistical heterogeneity, it is better not to perform a meta-analysis. In the eight studies used for the current meta-analysis, there is no statistical heterogeneity (e.g. p=0.36, I2= 9.1). The studies are, unfortunately, clinically and methodologically diverse; for instance, there is large variation among the included studies regarding recurrent hernia, diabetes, bilateral repair, use of local anaesthetics, and the surgeon’s level of expertise. To correct for this clinical and methodological diversity, the random method should be used rather than fixed analysis. Especially when the results of the fixed and random analysis conflict, as in the current situation, the choice of meta-analysis method should preferably be conservative, and in these situations the random method should also be used [27, 28]. An infection percentage in low-risk patients should be below 2% [29] when performing clean inguinal or femoral hernia surgery lasting less than 1 h. Therefore, the question should be, »Should we administer antibiotics to all patients undergoing clean surgery to spare a few (sometimes a very few) superficial wound infections?« [30]. Because a relatively simple treatment of wound drainage, frequently combined with antibiotics, is required for superficial infections, and because the rare deep infections result in a low number of mesh removals (0.09% [10] –1.1% [18]) with remarkably few hernia recurrences, there remains no routine indication for antibiotic prophylaxis in low-risk patients. Discarding the use of antibiotic prophylaxis in hernia repair could reduce costs, the risks of toxic and allergic side effects, and the possible development of bacterial resistance [13] or superinfections.

If a much higher percentage of wound infections exists because of patient or surgical characteristics [28], as demonstrated by two of the inguinal hernia studies, the use of antibiotic prophylaxis could be reevaluated. In the trials with high wound infection percentages, two important differences can be seen: The duration of surgery was 1.5 times longer (64 min), and drains were used more often (22%), both known risk factors for infection [29, 31]. This review shows the lack of randomised studies of laparoscopic groin hernia repairs on the subject of wound infection. The only laparoscopic inguinal hernia (transabdominal preperitoneal) repair study discussed 80 patients without proper randomisation (alternately), but it demonstrated no infections. This study virtually excludes the presence of a high percentage of wound infections in laparoscopic repair. There is some logic in this low infection rate since the minimally invasive approach consists of small and occluded incisions, although the operating time is an average of 18 min longer compared with an open repair [32]. Considering these aspects, and as long as hard evidence is lacking, it is probably acceptable to conclude that in laparoscopic inguinal hernia repair, no antibiotic prophylaxis is needed. It is not expected that important publications were missed in our thorough search of the literature and our contacts with authorities in the field. It is, however, difficult to assess the possibility of publication bias, resulting in studies being left out that showed no effect of antibiotic prophylaxis for the procedures included in our analysis. On the other hand, if publication bias exists, the effect of antibiotic prophylaxis would be even more modest than we found in our meta-analysis, as failure to include the grey literature has been reported to overestimate a treatment effect by 15% [33]. From this meta-analysis it can be concluded that in clinical settings with low rates of infection, there will be no significant benefit from using antibiotic prophylaxis for groin hernia repair in low-risk patients. Because of an unknown impact on bacterial resistance [13], the use of routine antibiotic prophylaxis in primary inguinal hernia repair should therefore be discouraged. In the Netherlands, the cost benefit for one patient is rel-

133 Chapter 17 · Does Antibiotic Prophylaxis Prevent the Occurrence of Wound Infection

⊡ Table 17.7. Patient and operation characteristics that may influence the risk of wound infections [28] Patient

Operation

Age Nutritional status Diabetes Smoking Obesity Coexistent infection at a remote body site Colonisation with microorganisms Altered immune response Length of preoperative stay

Duration of surgical scrub Skin antisepsis Preoperative shaving Preoperative skin prep Duration of operation Antimicrobial prophylaxis Operating room ventilation Inadequate sterilisation of instruments Foreign material in the surgical site Surgical drains Surgical technique

atively limited (€13.20) [34]. Nevertheless, because of the large number of inguinal hernia repairs performed in low-risk patients (an estimated 70% of all hernias) [21], discarding the use of antibiotic prophylaxis will save at least €10 million in Europe and the United States. There is, of course, not enough evidence regarding the high-risk group of patients (⊡ Table 17.7). To answer this question, another large trial would be needed, or, better yet, the source data of the separate trials should be analysed. Therefore, an attempt is currently being made to contact all authors of randomised controlled trials and ask them to deliver their source data for final analysis. Currently it can be stated that surgeons and hospitals must assess their own surgical site infection rates to define if prophylactic antibiotics must be widely used in all patients. For clinical settings with low rates of surgical site infections, selective use of antibiotics based on patients’ and surgical risk factors is probably the best therapeutic strategy.

Conclusion The meta-analysis of eight studies on the use of antibiotic prophylaxis for preventing wound infection after mesh groin hernia repair did not favour

17

the use of antibiotic prophylaxis: OR 0.59 (95% CI 0.34–1.03) and NNT 80 (49–1,111). From this meta-analysis it can be concluded that in clinical settings with low rates of infection, there will be no significant benefit from using antibiotic prophylaxis for groin hernia repair in lowrisk patients. However, if patient or surgical characteristics prove the existence of a much higher percentage of wound infections, as demonstrated by two of the inguinal hernia studies, the use of antibiotic prophylaxis could be reevaluated.

Acknowledgments The author wants to thank M. J. Koelemay, M.D., Ph.D., and M. P. Simons, M.D., Ph.D., for their help with this study.

References 1. Bay-Nielsen M, Kehlet M, Strand L, Malmstrom J, Andersen FH, Wara P, Juul P, Callesen T; Danish Hernia Database Collaboration (2001). Quality assessment of 26,304 herniorrhaphies in Denmark: a prospective nationwide study. Lancet 358:1124–1128 2. Arroyo A, Garcia P, Perez F, Andreu J, Candela F, Calpena R (2001). Randomized clinical trial comparing suture and mesh repair of umbilical hernia in adults. Br J Surg 88:1321–1323 3. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004). Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–585 4. Nilsson E, Haapaniemi S, Gruber G, Sandblom G (1998). Methods of repair and risk for reoperation in Swedish hernia surgery from 1992 to 1996. Br J Surg 85:1686–1691 5. Nyhus LM, Alani A, O’Dwyer PJ (2004). The problem: How to treat a hernia. In: Schumpelick V, Nyhus LM (eds) Meshes: benefits and risks, 1st edn. Springer, Berlin, pp 3–30 6. EU Hernia Trialists Collaboration (2000). Mesh compared with non-mesh methods of open groin hernia repair: systematic review of randomized controlled trials. Br J Surg 87:854–859 7. EU Hernia Trialists Collaboration (2002). Repair of groin hernia with synthetic mesh, meta-analysis of randomized controlled trials. Ann Surg 235:322–332 8. Lichtenstein IL, Shulman AG, Amid PK, Montller MM (1989). The tension-free hernioplasty. Am J Surg 157:188– 193 9. Stephenson BM (2003). Complications of open groin hernia repair. Surg Clin North Am 83:1255–1278

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10. Taylor SG, O’Dwyer PJ (1999). Chronic groin sepsis following tension-free inguinal hernioplasty. Br J Surg 86:562– 565 11. Sanchez-Manuel FJ, Seco-Gil JL (2004). Antibiotic prophylaxis for hernia repair. Cochrane Database Syst Rev 18(4):CD003769 12. Rutkow IM (2003). Demographic and socioeconomic aspects of hernia repair in the United States in 2003. Surg Clin North Am 83:1045–1051 13. Waldvogel FA, Vaudaux PE, Pittet D, Lew PD (1991). Perioperative antibiotic prophylaxis of wound and foreign body infections: microbial factors affecting efficacy. Rev Infect Dis 13 (suppl 10):S782–789 14. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996). Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12 15. Cochrane Review Manager 4.2.7. Available at http://www. cc-ims.net/RevMan 16. Schwetling R, Barlehner E (1998). Is there an indication for general perioperative antibiotic prophylaxis in laparoscopic plastic hernia repair with implantation of alloplastic tissue? Zentralbl Chir 123:193–195 17. Morales R, Carmona A, Pagán A (2000). Utility of antibiotic prophylaxis in reducing wound infection in inguinal or femoral hernia repair using polypropylene mesh. Cir Esp 67:51–59 18. Yerdel MA, Akin EB, Dolalan S, Turkcapar AG, Pehlivan M, Gecim IE, Kuterdem E (2001). Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial. Ann Surg 233:26–33 19. Celdran A, Frieyro O, de la Pinta JC, Souto JL, Esteban J, Rubio JM, Senaris JF (2004). The role of antibiotic prophylaxis on wound infection after mesh hernia repair under local anesthesia on an ambulatory basis. Hernia 8: 20–22 20. Oteiza F, Ciga MA, Ortiz H (2004). Antibiotic prophylaxis in inguinal herniaplasty. Cir Esp 75:69–71 21. Aufenacker TJ, van Geldere D, van Mesdag T, Bossers AN, Dekker B, Scheijde E, van Nieuwenhuizen R, Hiemstra E, Maduro JH, Juttmann JW, Hofstede D, van der Linden CT, Gouma DJ, Simons MP (2004). The role of antibiotic prophylaxis in prevention of wound infection after Lichtenstein open mesh repair of primary inguinal hernia. A multi-center double-blind randomized controlled trial. Ann Surg 240:955–961 22. Perez AR, Roxas MF, Hilvano SS (2005). A randomized, double-blind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension free mesh herniorrhaphy. J Am Coll Surg 200:393–398 23. Tzovaras G, Delikoukos S, Christodoulides G., Spyridakis M, Mantzos F, Tepetes K, Athanassiou E, Hatzitheofilou C (2007). The role of antibiotic prophylaxis in elective tension-free mesh inguinal hernia repair: results of a single centre prospective randomised trial. Int J Clin Pract 61 (2):236–239

24. Jain SK, Jayant M, Norbu C (2008). The role of antibiotic prophylaxis in mesh repair of primary inguinal hernias using Prolene hernia system: a randomised prospective double-blind control trial. Trop Doct 38(2):80–82 25. Horan TC, Gaynes RP, Martone WJ, Jaris WR, Emori TG (1992). CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Am J Infect Control 20:271–274 26. Tierney JF, Stewart LA (2005). Investigating patient exclusion bias in metaanalysis. Int J Epidemiol 34:79–87 27. Alderson P, Green S. Cochrane Collaboration open learning material for reviewers, version 1.1. Available at http:// www.cc-ims.net 28. Higgins JPT, Green S (eds). Cochrane handbook for systematic reviews of interventions, version 5.0.2 [updated September 2009]. The Cochrane Collaboration, 2009. Available at http://www.cochrane-handbook.org 29. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR (1999). Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol 20:247–280 30. Sitges-Serra A (2002). Ecosurgery. Br J Surg 89:387–388 31. Simchen E, Rozin R, Wax Y (1990). The Israeli study of surgical infection of drains and the risk of wound infection in operation for hernia. Surg Gynecol Obstet 170:331–337 32. Memon MA, Cooper NJ, Memon B, Memon MI, Abrams KR (2003). Meta-analysis of randomized clinical trials comparing open and laparoscopic inguinal hernia repair. Br J Surg 90:1479–1492 33. McAuley L, Pham B, Tugwell P, Moher D (2000). Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet 356:1228–1231 34. Z-index database of Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie (KNMP), The Hague, Netherlands. Available at http://www.knmp.nl [in Dutch]. Accessed December 2003

Discussion Klinge: Do you think that this problem of mesh infection and late mesh infection is an issue for meta-analysis and clinical studies? Aufenacker: It would be quite difficult to do the follow-up of such a study. If you want to prove the short-term effect of this infection, you need a large population. Simons: Do you think it would be good to use antibiotics in cases of patients with risk factors, such as smokers? Aufenacker: In our study, we do not look at smoking-related factors, so I can’t answer this question yet.

18

Infection Control in a Hernia Clinic: 24-Year Results of Aseptic and Antiseptic Measure Implementation in 4,620 »Clean Cases« Based on Up-To-Date Microbiological Research M. Deysine

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Chapter 18 · Infection Control in a Hernia Clinic

Introduction The wound infection rate for both ventral and inguinal herniorrhaphy has remained at virtually the same unacceptable level for the last 60 years: between 3% and 4% for inguinal hernias and between 8% and 14% for ventral hernias. Thus, approximately 30,000 inguinal and 3,000 ventral repairs become infected yearly in the United States alone, and European figures may be similar [2–3]. During the last 20 years the introduction of mesh repairs has considerably changed the prognosis of these infections, whose successful treatment requires a sequence of often crippling or even life-threatening reoperations [4]. This paper reports our 25-year experience with »clean« postherniorrhaphy wound infection prevention. During this period, vast advances have been made by groups studying the biological relationships among bacteria, prostheses, and hosts [5–8]. The emerging information solidly supports the application of seasoned surgical principles that function by diminishing the number of microbes entering the wound, decreasing their available food supply, and killing them with antibiotics [9, 10]. However, recent discoveries dealing with bacterial »quorum sensing« and its inhibitors may favorably apply to the prevention and treatment of infections related to surgically implanted foreign bodies. Our results suggest that with the application of up-to-date knowledge dealing with the interaction between biomaterials and bacteria, postherniorrhaphy wound infections may become a preventable complication.

Methods and Materials

18

In 1981 we created a hernia clinic where patients were treated under a protocol that has been reported elsewhere [11–12]. At the onset, we adopted the Shouldice technique for inguinal repairs, which was progressively replaced by mesh repairs using expanded polytetrafluoroethylene (ePTFE), polypropylene, and Dacron polyester meshes. Ventral herniorrhaphy underwent a similar evolutionary pattern [10].

Initially, the operating room aseptic and antiseptic measures used were the standard ones for so-called clean cases. Wounds were not irrigated, and we did not use intravenous antibiotics. In 1982, after the occurrence of five almost consecutive postinguinal herniorrhaphy wound infections, we modified our protocol by enhancing strict aseptic measures created by others. In addition, patients received a preoperative intravenous injection of 1 g cefazolin. We also irrigated the operative sites with a solution of 80 mg gentamicin sulfate diluted into 250 ml normal saline solution, starting immediately after opening the external oblique aponeurosis and continuing intermittently until the skin was closed. (See ⊡ Table 18.1). Postoperatively, patients were seen by the author at 7 days, at 1 month, and at yearly intervals thereafter. Wound infection was defined as the appearance of pus or any other exudate anywhere in a wound, any time after surgery.

Results Since 1981 we have performed 4,300 »clean« inguinal herniorrhaphies under a published protocol. We used the Shouldice technique in 2,500 and mesh or plug repair for the rest. Five postinguinal herniorrhaphy wound infections occurred (11%), the last one in 1982. All of them occurred in patients operated with the Shouldice technique. Four of the wounds grew coagulase-positive Staphylococcus aureus. All infections were treated by opening the skin from end to end and the wound down to the infected layer, with extensive debridement of all necrotic tissue and suture material. Wounds were irrigated at daily intervals with normal saline solution, and the patients received short-term courses of specific antibiotics. All wounds healed by secondary intention. Two patients developed recurrences and were reoperated 6 weeks after the wounds were completely healed. Three hundred and thirty »clean« ventral herniorrhaphies were performed utilizing a variety of mesh techniques and materials. Three patients in whom the defects were corrected with ePTFE meshes developed wound infections (0.9%) requiring mesh removal. All of these wounds grew coagulase-positive Staphylococcus aureus. These

137 Chapter 18 · Infection Control in a Hernia Clinic

⊡ Table 18.1. Aseptic and antiseptic measures adopted in 1982 to decrease wound contamination by operating room environmental bacteria In the preoperating room: 1. Patient’s abdomen is shaved or clipped just before surgery 2. Patient receives 1 g intravenous cefazolin In the operating room: 1. Team emphasis on measures to prevent prosthesis contamination 2. Team awareness of operating room preparations: face masking, scrubbing, gowning, gloving, instrument package handling 3. Double gloving, with changes of the external glove every 45 min 4. Avoidance of nonessential personnel traffic through the operating room 5. Team awareness of all moves that may produce contamination Surgical measures 1. Ensure that skin preparation vastly exceeds the wound area; include the scrotum for inguinal herniorrhaphy 2. Drape the patient carefully 3. Emphasize scissors or scalpel dissection 4. Use electrocautery sparsely 5. Keep dissection circumscribed to relevant areas 6. As soon as the external oblique aponeurosis is opened (for inguinal or ventral hernias), start wound irrigations with a solution of 80 mg gentamicin sulfate dissolved in 250 ml normal saline 7. Irrigate as often as possible 8. Approximate tissues to themselves and to the prosthesis, using the minimum tension necessary to permit appropriate contact and avoid tissue strangulation 9. Place the prosthesis into the gentamicin solution as soon as it leaves the package; consider the operating room air to be contaminated with bacteria 10. Avoid excessive retraction, clamping, or tissue crushing with any kind of instrument 11. Avoid hand retracting or dissection 12. Excise all devitalized tissue 13. Before closing the external oblique aponeurosis, debride the wound with a dry gauze to remove clots, separated fat tissue, etc. 14. Avoid drain placement; if needed, use it for only 24 h, and keep the patient on intravenous antibiotics all of that time

patients were reoperated 6–12 months later using various techniques. No infections were observed in »clean cases« receiving either polypropylene or Dacron polyester meshes [10].

18

Since the inception of these aseptic and antiseptic measures in 1982, we have not experienced wound infections in »clean« inguinal or ventral hernia repairs

Discussion After the landmark work of Semmelweis, Pasteur, and Lister, the wound infection rate for »clean« general surgical cases fell from virtually 100% to about 10%. This rate was further reduced around 1950 to approximately 4% by improvements in operating room aseptic and antiseptic measures plus the introduction of perioperative and postoperative antibiotics. However, no further improvement in the »clean« wound infection rate has been recorded for the last 40 years [4]. This situation may be the result of less than optimal implementation of timetested aseptic measures associated with a false sense of security emerging from antibiotic availability. Furthermore, the actual wound status terminology may be deceiving because so-called clean wounds are far from sterile. Abundant evidence in the literature demonstrates that such wounds contain bacteria at the time of closure, coming from the air, bodies, or surgical instruments. Hubble et al. demonstrated that operating room air might contain up to 1,000 colony-forming units per mm3 [13]. Taylor and Bannister showed that a surgeon leaning over a wound increases the bacterial wound count by 27-fold [14], and Dillon et al. showed that 23% of »clean wounds« grew bacteria and that postoperative infections of those wounds were 10 times more common [15]. This means that during »clean« surgery, both the wound and the prosthesis will become contaminated by bacteria to various degrees. However, our knowledge of wound infection has rapidly increased because, during the last 30 years, biochemical engineers, microbiologists, and general and orthopedic surgeons have clarified the interactions among bacteria, host tissues, and prosthetic polymers [5–8, 16–19]. As demonstrated by several investigators [14–16], bacteria will enter a wound from a variety of operating theater sources. These microorganisms depend on food substrate for their survival,

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Chapter 18 · Infection Control in a Hernia Clinic

and mortified tissue and plasma-coated prosthetic polymers meet this nutritional demand [20]. Subsequently, by producing high-quality adhesives that allow their survival and further colonization, bacteria rapidly hold fast to those nourishing surfaces. The forthcoming colonization is then followed by a host–immune response leading to suppuration [5, 6, 8]. In 1970, Nealson et al. [21] reported on the cellular control of the synthesis and activity of a bacterial luminescent system regulated by a system of intercellular communications. This led to a series of discoveries demonstrating that grampositive and gram-negative bacteria communicate with each other by releasing chemical molecules called autoinducers, which regulate gene expression in response to changes in population density. This process allows bacteria to build community structures and regulate biofilm and toxin production. In essence, the quorum sensum is responsible for bacterial contamination of tissues and biomaterials plus further toxin production. These landmark discoveries led to the identification of an autoinducer RAP (33–kDa autoinducer RNAIII-activating protein), which induces the phosphorylation of the target of RAP (TRAP). TRAP is a 21–kDa protein that regulates the expression of toxins. Most importantly, in the absence of TRAP expression of phosphorylation, bacteria do not produce toxins, and they fail to cause disease. Recently, the quorum-sensing inhibitor RIP [RNAIII-inhibiting peptide (YSPWTNF–NH2)] showed the capacity to inhibit TRAP phosphorylation, thereby preventing infection of implanted devices in several animal models. Finally, RIP has been found to have significant activity in treating methicillin-resistant staphylococcal infections in a rat model, suggesting its use as a therapeutic constituent. From these data, it is evident that a new era of infection control and treatment may be emerging. In 1982 we decided to test the effect of irrigating inguinal herniorrhaphy wounds with a concentrated solution of gentamicin sulfate. In addition, the prosthesis was placed in the gentamicin solution directly from the package and from there into the wound. Further to this, a preoperative intravenous injection of 1 g cefazolin was added to

the protocol. The killing effect of the gentamicin is concentration dependent and is followed by a bacteriostatic effect. Although it is most effective against gram-negative bacteria, gentamicin also has killing activity against staphylococci, both S. aureus and S. epidermidis. The empirical choice of a highly concentrated gentamicin solution may explain our results because, at the level used, gentamicin would be bactericidal and not bacteriostatic [22]. Most important, because gentamicin shows antimicrobial synergy when used in combination with beta-lactams, the cefazolin may have contributed to successful bacterial killing [23]. Gentamicin is not harmless and can produce auditory and renal damage at high serum concentrations. Concerned about such side effects, we measured gentamicin serum levels in 10 consecutive postinguinal herniorrhaphy patients 1 h postoperatively and found undetectable levels. Ventral herniorrhaphies, in contrast, present a larger surface; for those cases, we recommend avoiding peritoneal contact with the gentamicin solution because it will be rapidly absorbed by the serosal surface. Compresses soaked in the gentamicin solution can be used to protect the wound edges while or until the peritoneum is closed, at which time wound irrigations can continue. We have not encountered any cases of otic or renal toxicity. Salvati and others have monitored serum gentamicin levels after the treatment of infected orthopedic wounds with pellets containing the antibiotic, showing minimal or no detectable levels [24–27]. Recently, gentamicin irrigations have been successfully used by neurosurgeons to prevent postcraniotomy infections [28]. Additionally, Junge et al. successfully bonded gentamicin to polyvinylidene fluoride mesh material, demonstrating that the antibiotic retained its antimicrobial activity after implantation. These findings open the possibility of creating a mesh that could resist microbial colonization [29]. The use of preoperative intravenous antibiotics is a much debated issue [30–39]. In spite of the controversy, we choose to use them because we believe it could balance the infection struggle in our patients’ favor. Inguinal herniorrhaphy is one of the few surgical procedures in which the surgeon deals with

139 Chapter 18 · Infection Control in a Hernia Clinic

initially sterile tissues. Therefore, the amount of bacteria present at closure should become a controllable factor. Consequently, in addition to the antibiotic regimen, we strictly emphasized aseptic measures developed by others because we believed in their usefulness. Patients were shaved by the surgeon just before surgery, and the skin preparation vastly exceeded the operative site. Gowning, gloving, and draping were strictly supervised to diminish errors [40–43]. The literature on gloving is rich in data demonstrating that those devices routinely perforate [44–46]. Therefore, we used double gloving. Electrocautery produces a time- and energydependent coagulation necrosis indistinguishable from a full-thickness burn [47–50]. To lessen the amount of necrotic material in the wound, we used such tools sparingly. Incision and further dissection were performed with scalpel and delicate scissors. Gentle tissue handling and retracting were encouraged. The interpretation of these results is limited by the logistics of the clinical problem: These patients could have been randomized; thus, we do not know whether any of the above measures would, by themselves, have been sufficient to improve our patients’ outcomes. Moreover, our success cannot be attributed to the use of antibiotics only, as other measures were included to decrease the number of bacteria entering the wound. Additionally, the field of ventral herniorrhaphy poses additional challenges, probably related to the fact that larger wounds require larger meshes. For these operations we strongly recommend the incorporation of measures that have already yielded vastly improved results in the field of orthopedic infections, including dedicated operating rooms with HEPA-filtered laminar air flow, hooded and ventilated gowns and masks, and double gloving [51]. In our hands, the implementation of strict aseptic measures, atraumatic technique, minimal electrocautery use, intravenous preoperative antibiotics, and early and frequent wound irrigation with a gentamicin solution have eliminated postoperative herniorrhaphy infections. The validity of these results can henceforth be substantiated only by further studies.

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New discoveries by microbiologists may further enhance the field of infection prevention and treatment.

References 1. Bendavid R (2004) Recurrences, the fault of the surgeon. In: Shumpelick V, Nyhus LM (eds) Meshes: benefits and risks. Springer, Berlin, pp 51–62 2. Deysine M (2004) Historical evolution of asepsis and antisepsis. In: Deysine M (ed) Hernia infections: pathophysiology, diagnosis treatment and prevention. Dekker, New York, pp 1–16 3. Sanchez Montes I, Sanchez Montes J, Deysine M (2004) Epidemiology and incidence of post external abdominal wall herniorrhaphy. In: Deysine M (ed) Hernia infections: pathophysiology, diagnosis treatment and prevention. Dekker, New York, pp 17–57 4. Deysine M (1998) Pathophysiology, prevention and management of prosthetic infections in hernia surgery. Surg Clin North Am 78:1105–1115 5. Gristina AG, Oga M, Well LX, et al. (1985) Adherent bacterial colonization in the pathogenesis of osteomylitis. Science 228:990–993 6. Patti JM, Allen BL, McGavin MJ, et al. (1994) MSCRAMMmediated adherence of microorganisms to host tissues. Annu Rev Microbiol 48:585–617 7. Shive MS, Hasan SM, Anderson JM (1999) Shear stress effect on bacterial adhesion, and leukocyte oxidative capacity on polyetherurethane. J Biomed Mater Res 46:511– 519 8. Bryers JD (2000) Biofilms II–process analysis and application. Wiley Interscience, New York 9. Salvati EA, Gonzalez Della Valle A, Masri BA, Duncan CP (2003) The infected total hip arthroplasty. Instr Course Lect 52:223–245 10. Deysine M (1998) Ventral herniorrhaphy: treatment evolution in a hernia service. Hernia 2:15–18 11. Deysine M (1991) Inguinal herniorrhaphy. Reduced morbidity by service standardization. Arch Surg 126:628–630 12. Deysine M (2001) Hernia clinic in a teaching institution: creation and development. Hernia 5:65–69 13. Hubble MJ, Weale AE, Perez JV, et al. (1996) Clothing in laminar-flow operating theaters. J Hosp Infect 32:1–7 14. Taylor GJ, Bannister GC (1993) Infection and interposition between ultraclean air source and wound. J Bone Joint Surg 75B:503–504 15. Dillon ML, Postlethwait RW, Bowling KA (1969) Operative wound cultures and wound infections: a study of 342 patients. Ann Surg 170:1029–1034 16. Charnley J, Efrekhar N (1969) Postoperative infection in total prosthetic arthroplasty of the hip joint. Br J Surg 56:641–649 17. Lidwell OM, Lowbury EJ, Whyte W, et al. (1982) Effect of ultraclean air in operating rooms on deep sepsis in the

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joint after total hip or knee replacement: a randomised study. Br Med J 285 :10–14 Lidwell OM, Lowbury EJL, Whyte W, et al. (1983) Airborne contamination of wounds in joint replacement operations: the relationship to sepsis rates. J Hosp Infect4:111– 131 Subcommittee of the Committee on Control of CrossInfection (1962) Operating-theatre hygiene. Design and ventilation of operating-room suites for control of infection. Lancet 2:945–951 Deysine M (2004) Prevention. In: Deysine M (ed) Hernia infections: pathophysiology, diagnosis, treatment and prevention. Dekker, New York, pp 301–324 Nealson KH, Platt T, Hastings JW (1970) Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 104:313–322 Lortholary O, Tod M, Cohen Y, et al. (1995) Aminoglycosides in antimicrobial therapy II. Med Clin North Am 79:761–787 Drugeon HB, Caillon J, Juvin ME, et al. (1988) Bases theoriques de l’association de la cefazidine avec les autres antibiotiques. Recherche de synergie. Presse Med 17:1900 Salvati EA, Callaghan JJ, Brause BD, et al. (1986) Reimplantation in infection. Elution of gentamicin from cement and beads. Clin Orthop Relat Res 207:83–93 Dirschl DR, Wilson FC (1991) Topical antibiotic irrigation in the prophylaxis of operative wound infections in orthopedic surgery. Orthoped Clin North Am 22:419–426 Wahlig H, Dingeldein E, Bergmann R, et al. (1978) The release of gentamicin from polymethylmethacrylate beads. J Bone Joint Surg 60B:270–275 Voos K, Rosenberg B, Fagrhi M, et al. (1999) Use of Tobramicin impregnated polymethylmethacrylate pin sleeves for the prevention of pin-tract infection in goats. J Orthoped Trauma 13:98–101 Yamamoto M, Jimbo M, Ide M, et al. (1996) Perioperative antimicrobial prophylaxis in neurosurgery: clinical trial of systemic Flomex administration and saline containing gentamicin for irrigation. Neurol Med Chir (Tokyo) 36:370–376 Junge K, Rosh R, Klinge U, et al. (2005) Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis. Biomaterials 26:787–793 Waldogel FA, Vaudaux PE, Pittet D, et al. (1991) Perioperative antibiotic prophylaxis of wound and foreign body infections: microbial factors affecting efficacy. Rev Infect Dis 13 (suppl):782–789 Classen DC, Scott Evans R, Pestotnik SL, et al. (1992) The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 326:281–286 Wong-Beringer A, Corelli RL, Schrock TR, et al. (1995) Influence of timing of antibiotic administration on tissue concentrations during surgery. Am J Surg 169:379–381 Hill C, Mazas F, Flamant R, et al. (1981) Prophylactic cefazolin versus placebo in total hip replacement. Lancet 1:795–797

34. Troy MG, Quan-Sheng Dong, Dobrin PB, et al. (1996) Do topical antibiotics provide improved prophylaxis against bacterial growth in the presence of polypropylene mesh? Am J Surg 171:391–393 35. Gürleyik E, Gürleyik G, Cetinkaya F, et al. (1998) The inflammatory response to open tension-free inguinal hernioplasty versus conventional repairs. Am J Surg 175:179– 182 36. Musella M, Guido A, Musella S (1998) Collagen tampons as aminoglycoside carriers to reduce postoperative infection rate in prosthetic repair of groin hernia. Eur J Surg 2001; 167:130–132 37. Hopkins CC (1991) Antibiotic prophylaxis in clean surgery, peripheral vascular surgery, non cardiovascular thoracic surgery, herniorrhaphy and mastectomy. Rev Infect Dis 13 (suppl):869–873 38. Abramov D, Jeroukhimov I, Yinnon AM (1996) Antibiotic prophylaxis in umbilical and incisional hernia repair. Eur J Surg 162:945–948 39. Gilbert AI, Felton LL (1993) Infections in inguinal hernia repair considering biomaterials and antibiotics. Surg Gynecol Obstet 177:126–130 40. Dineen P (1978) Hand-washing degerming: a comparison of povidone–iodine and chlorhexidine. Clin Pharmacol Ther 23:63–67 41. Von Bergmann E, von Bruns P, von Mikulicz J (1904) A system of practical surgery. Lea Brothers, New York 42. Watson-Jones R (1955) Fractures and joint injuries, 4th edn. Livingstone, Edinburgh, pp 191–197 43. Hochberg J, Murray GF (1997) Principles of operative surgery. In: Sabiston DC, Lyerly HK (eds) Textbook of surgery. The biological basis of modern surgical practice, 15th edn. Saunders 44. Rutkow IM (1999) The surgeon’s glove. Arch Surg 134:223– 224 45. Sohn RL, Murray MT, Franko A (2000) Detection of surgical glove integrity. Am Surgeon 66:302–306 46. Muto CA, Sistrom MG, Strain BA (2000) Glove leakage rates as a function of latex content and brand. Arch Surg 135: 982–985 47. Porter KA, O’Connor S, Rimm E, et al. (1998) Electrocautery as a factor in seroma formation following mastectomy. Am J Surg 176:8–11 48. Onbargi LC, Hayden R, Valle RF, et al. (1993) Effects of power and electrical current density variations in an in-vitro endometrial ablation model. Obstet Gynecol 82:912–918 49. Madden JE, Edlich RF, Custer JR, et al. (1970) Studies in the management of the contaminated wound. IV. Resistance to infection of surgical wounds made by knife, electrosurgery and laser. Am J Surg 119:222–224 50. Olivar AC, Forouhar FA, Gillies CG, et al. (1999) Transmission electron microscopy: evaluation of damage in human oviducts caused by different surgical instruments. Ann Clin Lab Sci 29:281–285 51. Deysine M (2004) Post mesh herniorrhaphy control: are we doing all we can? [letter] Hernia 8:90–91 Discussion

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Discussion Smeds: What are the reasons for your low infection rate? Deysine: It’s a combination of things I did. First of all, I try to get my operating room sterile, and I use prophylactic antibiotics because it makes sense to me. It’s only one injection; it works in orthopedic patients. Kehlet: We hear about these large personal series with zero problems in anything. And then we have these series from randomized studies with infection rates up to 9%. How can we proceed, because there is a discrepancy between these difference experiences? Deysine: I believe in technique, and I think that doing this kind of operation properly without additional damage of tissue leads to these good results.

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Components Separation Technique: Pros and Cons B. M. van der Kolk, T. S. de Vries Reilingh, O. Buyne, R. P. Bleichrodt

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Introduction

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of the muscles to restore the anatomy of the ventral abdominal wall. The method and its modifications have been described in detail by Bleichrodt and coworkers [5–8]. This chapter describes the relevant anatomy of the ventral abdominal wall and the surgical technique, summarizes the results, and discusses the sequelae and possible solutions to prevent them.

Prosthetic repair is still the most frequently applied method to repair ventral hernias. However, prosthetic materials have several drawbacks. First, the mechanical properties of the abdominal wall may be altered, providing less dynamic support and a less favorable cosmetic result owing to bulging of the prosthesis. Second, the prosthetic material may cause damage to the intraabdominal viscera if the peritoneum or greater omentum cannot be interposed between the prosthesis and the organs [1]. Third, biomaterials increase the risk of infection, particularly when they are used for reconstruction in a contaminated environment, such as the abdominal wall in the presence of an enterocutaneous fistula [2, 3]. In 1990, Ramirez et al. [4] described a technique for reconstructing abdominal wall defects without using prosthetic material. It is based on enlargement of the abdominal wall surface by translation of the muscle layers to bridge fascial defects of up to 28 cm at the waistline without compromising the innervation and blood supply

The anatomy in relation to the components separation technique (CST) has been described by Bleichrodt et al. [5] and is summarized here. The skin and subcutaneous tissue cover the muscles of the ventral abdominal wall. The muscles of the ventrolateral abdominal wall are the external oblique, internal oblique, and transversus abdominis, which insert into the anterior and posterior sheaths of the rectus abdominis muscle (⊡ Fig. 19.1). The arterial blood supply of the skin comes mainly from the intercostal arteries and the perforating branches of the epigastric artery (⊡ Fig. 19.2). The innerva-

⊡ Fig. 19.1. Anatomy of the abdominal wall. The skin and subcutaneous tissue cover the muscles of the ventral abdominal wall. The muscles of the ventrolateral abdominal wall are the external oblique, internal oblique, and transversus abdominis, which insert into the anterior and posterior sheaths of the rectus abdominis muscle. The aponeurosis of the external oblique muscle forms the anterior rectus sheath. The internal oblique aponeurosis divides into an anterior and posterior

part. The anterior part forms the anterior layer of the rectus sheath, together with the external oblique muscle. The posterior part fuses with the transversus abdominis, forming the posterior rectus sheath, superior to the linea semilunaris. The neurovascular bundle runs between the internal oblique and transversus abdominis muscle and penetrates the posterior rectus sheath at the posterolateral side. (Reproduced with permission from Bleichrodt et al. [5])

Anatomy

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⊡ Fig. 19.2. Blood supply of the skin and muscles of the ventral abdominal wall. The blood supply of the ventral abdominal wall stems mainly from the epigastric and intercostal arteries. The skin of the ventral abdominal wall is supplied by the (a) periumbilical musculocutaneous perforators of the (b) superior and (c) inferior epigastric arteries and the (d)

intercostal arteries, but also by branches of the superficial epigastric artery and the superficial circumflex iliac and external pudendal arteries (c). The blood supply of the muscular layers of the abdominal wall stems from the (e) superior and (f) inferior epigastric arteries, together with the intercostal arteries (g). (Reproduced with permission from Bleichrodt et al. [5])

tion of the anterolateral ventral abdominal wall is shown in ⊡ Fig. 19.3. The muscles are innervated by the 7th–12th intercostal nerves and the iliohypogastric and ilioinguinal nerves.

abdomen, 7–10 cm at the waistline, and 1–3 cm in the lower abdomen. A further gain of 2–4 cm can be achieved by separating the posterior sheath of the rectus abdominis muscle. The abdominal wall is closed in the midline with a running suture of a nonabsorbable or slowly absorbable suture material. Suction drains are placed subcutaneously, and the subcutis and skin are closed. Defects of up to 28 cm in the waistline can be bridged in this way. After closure of the linea alba, the external oblique muscle and the posterior rectus sheath are retracted laterally.

Components Separation Technique (⊡ Fig. 19.3a–e)

The skin and subcutaneous fat are dissected free from the anterior rectus sheath and the aponeurosis of the external oblique muscle. By doing this, the perforating branches of the epigastric artery are transected. The aponeurosis of the external oblique muscle is incised 1–2 cm lateral to the lateral border of the rectus abdominis muscle. The myoaponeurosis of the external oblique muscle is transected longitudinally over its full length. Transection includes the muscular part of the external oblique muscle on the thoracic wall. With this extension, the rectus abdominis muscle can be maximally shifted medially in the upper abdomen. The external oblique muscle is separated from the internal oblique muscle in the avascular plane between both muscles. With this technique, the rectus muscle can be advanced 3–5 cm in the upper

Overall Results The results of CST up to 2007 were reviewed by de Vries Reilingh et al. [8]. Operative technique, complications, and recurrence rates were the main points of interest. As of 2007, 15 series had been published on the results of abdominal wall repair using CST: one randomized controlled trial and 14 retrospective series. The technique varied among the studies. In all studies, transection of the external oblique muscle was performed; in six, a release of the posterior rectus sheath was carried out as

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⊡ Fig. 19.3. The neurovascular bundle in relation to the abdominal wall musculature. The muscles of the anterolateral ventral abdominal wall are innervated by the 7th–12th intercostal nerves and the iliohypogastric and ilioinguinal nerves. The nerves (a) run forward together with the accompanying arteries and veins between the internal oblique (b) and the transversus abdominis (c) muscle. Branches are supplied to the muscle and the overlying skin (d). The segmental neu-

rovascular bundles penetrate the internal oblique contribution to the posterior rectus sheath at the posterolateral side to supply the rectus muscle (g) and the overlying skin. The neurovascular bundles enter the rectus sheath close to the axis of the epigastric arteries, about 10–25 mm medially from the lateral border of the rectus sheath (e). (Reproduced with permission from Bleichrodt et al. [5])

well. Two studies described an extension of the original technique [6, 7]: a release of the anterior rectus sheath in one series and transection of the transverse abdominal muscle in selected patients. In three series, incidental prosthetic onlay mesh support was used. The overall quality of the studies was moderate according to the MINORS criteria. One prospective randomized trial comparing CST and prosthetic repair was performed, having a MINORS index of 12. Fourteen retrospective series including 460 patients were published, with a mean MINORS index of 7 (range 3–8). Eleven retrospective studies with a MINORS index ≥5 were pooled with the 19 patients in the randomized controlled trial, giving a total of 479 patients [9–20]. Overall mortality was 1.2% (three out of 248 patients in seven series). Wound complications were observed in 12 series that included 354 patients. Wound complications were found in 23.8% [95% confidence interval (CI) 18.3–29.8]. Wound

infection was the most common complication, found in 18.9% (95% CI 14.9–23.2); seroma in 2.4% (95% CI 1.0–4.2); hematoma in 2.4% (95% CI 1.0–4.2); and skin necrosis in 1.5% (95% CI 0.5–3.1). A follow-up period of at least 1 year after operation was reported in five series that included 134 patients; 27 patients (18.2%; 95% CI 5.4–36.2) had a recurrent hernia.

Sequelae and Prevention Hematoma, Seroma, and Wound Infection When performing CST, a very large subcutaneous wound surface, approaching 1,000 cm2, is created, extending from the thorax to the inguinal region and in the lateral direction to the midaxillary line on both sides. Hematoma (2.4%), seroma (2.4%), infection (18.9%), and skin necrosis are the most

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frequent complications and account for 23.8% of postoperative complications. Hematomas can be prevented by meticulous hemostasis. Seroma formation is much more difficult to prevent. The inflammatory response, which is part of the wound healing process, creates an exudate between the fascia and the subcutaneous fat layer. Many techniques such as vacuum drains, subcutaneous sutures, fibrin glue, and compression bandages are insufficient. Most seromas are asymptomatic and will disappear within 3–6 months. Some seromas become very large and endanger the wound healing process in the early phase. If not drained properly, these seromas will drain spontaneously through the skin incision, with the risk of secondary infection. Chronic seromas can be successfully punctured, and surgery is seldom required. Many CST procedures are performed under contaminated conditions, which may explain the relatively high wound infection rate. CST is often performed in the presence of wounds, enterostomies, and even bowel fistulas. Providing adequate antibiotic prophylaxis, diminishing the dissection subcutaneously, and sparing the perforating epigastric arteries may all contribute to a better result.

Skin Necrosis The blood supply of the ventral abdominal wall stems mainly from the epigastric and intercostal arteries. Transection of the epigastric perforating arteries endangers the blood supply of the skin of the ventral abdominal wall. Especially in patients in whom the intercostal arteries have been transected–such as in patients with enterotomies or laparotomies via transverse incisions– ischemia or even skin necrosis may occur. Skin necrosis has been observed in 1.5% of patients in the literature. Necrosis is mainly located in the infraumbilical region in the midline. This complication can be prevented by sparing the periumbilical epigastric perforators. In our series of patients, 5% suffered skin necrosis when the classical technique was performed. Skin necrosis did not occur in any of the patients in whom the perforating arteries were spared. In our series,

19

skin necrosis occurred in all patients who were on chronic hemodialysis.

Bulging and Abdominal Wall Rupture Bulging of the abdominal wall at the side of the relaxing incisions in the external oblique myoaponeurosis may be a cosmetic problem in patients with a thin subcutaneous fat layer. Because the cosmesis of the abdominal wall improves considerably after CST and because most patients have a prominent subcutaneous fat layer, the vast majority of patients do not complain about the distinct swelling on the lateral side of the rectus abdominis muscle. Rupture of the abdominal wall at the side of the relaxing incision is, however, a very serious complication of the technique, causing damage to the neurovascular bundle, including the intercostal nerves, which results in paralysis of at least the rectus abdominis muscle. Since 2000 we have encountered three patients (<1%) with an abdominal wall rupture at the site of incision in the external oblique muscle. In one of those patients, the rupture occurred during operation and was repaired with mesh immediately. In the second patient, the rupture occurred the day after surgery and was repaired with a mesh as well. In the third patient, bilateral ruptures occurred 1 h and 1 week after the initial operation, respectively (⊡ Fig. 19.4). The hernia was repaired by primary closure and a sublay mesh. In two of the three patients, no herniation had occurred after 1 and 6 years, respectively. In the patient with an abdominal wall rupture on both sides, the reconstruction on the left side, which was performed 6 days after the index operation, was complicated by infection and herniation. Definitive repair was done 1 year later. The cause of rupture is unknown. It is essential to properly identify the plane between the internal and external oblique muscles. Accidental transection of the internal oblique muscle may result in an abdominal wall rupture because the transversus abdominis muscle is too weak to resist the intraabdominal pressure. Some surgeons advocate an onlay mesh support to prevent recurrent hernias or abdominal wall rupture [22].

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⊡ Fig. 19.4. Components separation technique. The patient is placed in a supine position. The skin is opened via a midline incision. If a skin defect exists or if the intestine is covered with a split-thickness skin graft, the abdominal cavity is entered via an incision just lateral to the defect. The intestine and other viscera are dissected free from the ventral abdominal wall. By doing this, the lateral border of the rectus abdominal muscle can be identified properly from the inside of the abdomen. a The skin and subcutaneous fat are dissected free from the anterior rectus sheath and the aponeurosis of the external oblique muscle to about 5 cm lateral to the lateral border of the rectus sheath. Mobilization includes transection of the epigastric perforators endangering the blood supply of the skin. b The aponeurosis of the external oblique muscle is incised 1–2 cm lateral to the lateral border of the rectus abdominis muscle. The myoaponeurosis of the external oblique muscle is transected longitudinally over its full length. Transection includes the muscular part of the external oblique muscle on the thoracic wall that extends at least 7–10 cm cranially.

c The external oblique muscle is separated from the internal oblique muscle in the avascular plane between both muscles, superiorly to the midaxillary line. Mobilization is essential because the fibrous interconnections between both muscles prevent optimal medial shift of the rectus abdominis muscle. d A further gain of 2–4 cm can be achieved by separating the posterior sheath of the rectus abdominis muscle. The posterior sheath is incised posteriorly, near the midline over its full length. The rectus abdominis muscle can easily be separated from the posterior rectus sheath. e Attention must be paid to not damage the neurovascular bundle laterally. Note the entrance of the neurovascular bundle that penetrates the fascia of the internal oblique muscle at a variable distance from the lateral border of the rectus abdominis muscle, near the axis of the epigastric artery. Damage to the neurovascular bundle results in denervation of the rectus abdominis muscle. The abdominal wall is closed in the midline with a running suture of a nonabsorbable or slowly absorbable suture material (after Bleichrodt et al. [5])

Nerve Damage

between the internal oblique and the transversus abdominis muscle, and branches are given to each muscle and the overlying skin. After CST, all patients have hyposensibility of the ventral abdominal wall skin as a result of transection of the sensory nerves. Denervation of the muscles of the ventral

The muscles of the anterolateral ventral abdominal wall are innervated by the 7th–12th intercostal nerves and the iliohypogastric and ilioinguinal nerves (⊡ Fig. 19.3). The nerves run forward together with the accompanying arteries and veins

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abdominal wall occurs less frequently. Damage to the nerves that innervate the rectus abdominis muscle may occur after accidental transection. This may occur when dissection is performed in the wrong plane between the internal oblique muscle and the transverse abdominis muscle, but also at the entrance of the nerves into the rectus sheath at the posterolateral side of the rectus sheath. After CST, some patients have radiating pain in the ventral abdominal wall for 6–12 months postoperatively. The cause of this pain is unknown. Stretching of the nerves may be one explanation.

Reherniation

b

c

⊡ Fig. 19.5. Rupture of the abdominal wall at the site of the relaxing incision in the myoaponeurosis of the external oblique muscle. a Swelling of the abdominal wall that occurred within 1 h of repair using the components separation technique. b At operation, a complete rupture of the abdominal wall musculature was found at the lateral border of the rectus abdominis muscle. c Note that the neurovascular bundle is damaged as well, resulting in (partial) denervation of the abdominal wall musculature (adapted from de Vries Reilingh and Bleichrodt [21] with permission)

Reherniation after CST is rather frequent. After a follow-up of at least 1 year, 18.2% had a recurrent hernia. This percentage is probably actually higher and approaches the results of suture repair. Most recurrences are located in the upper abdomen and are small. Modifying the CST technique may reduce the incidence of reherniation. Tension-free repair can be achieved in most patients when complete transection of the external oblique myoaponeurosis is performed, including mobilizing the rectus abdominis muscle from the thoracic wall. Recurrences can be repaired laparoscopically in most cases. Recurrence rates in hernia surgery are lower after mesh repair. This may be the case in CST as well [21]. Placement of a mesh is simple when the posterior sheath of the rectus abdominis muscle can be closed primarily; then the mesh can be positioned between the posterior rectus sheath and the rectus abdominis muscle (⊡ Fig. 19.6a). When the posterior sheath cannot be closed, the gap in the posterior rectus sheath is bridged with a mesh, preferably with an antiadhesive layer against adhesions, such as Proceed mesh or Sepramesh (⊡ Fig. 19.6b). The anterior sheath and rectus abdominis muscles are then closed primarily and cover the mesh. In 2006, a randomized controlled trial was initiated to determine whether a preperitoneal retromuscular mesh in combination with CST lowers recurrence rates. Kingsnorth et al. [22] combine CST with onlay

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a

reherniation rate is still high but may be decreased by combining CST and mesh repair.

References b

⊡ Fig. 19.6. Combined components separation technique and prosthetic repair following the Stoppa–Reeves technique. a The mesh is positioned preperitoneally to separate the intestine from the mesh and is covered by the rectus abdominis muscle. b When the posterior rectus sheath cannot be closed primarily, the gap is bridged by a double-layered mesh that protects the intestine from contact with the mesh

mesh repair. They report low complication and recurrence rates.

The Remaining Fascial Gap In approximately 7% of patients, the fascia cannot be closed in the midline. Further research is needed to identify those patients in whom the abdominal wall cannot be closed primarily. If primary closure is not possible, the fascial gap is bridged with a mesh under clean or clean-contaminated conditions. Otherwise, repair with the use of autologous tissue such as free or pedicled fascia flaps is performed.

Conclusion

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CST is an attractive technique for abdominal wall reconstruction in patients with large midline hernias, especially in a contaminated field. The technique restores the anatomy of the abdominal wall and has good cosmetic results. Postoperative complications are rather frequent. Morbidity may be decreased by sparing the epigastric perforating arteries and diminishing the wound surface. The

1. Basoglu M, Yildirgan MI, Yilmaz I, et al. Late complications of incisional hernias following prosthetic mesh repair. Acta Chir Belg 2004; 104:425–428 2. Burger JW, Luijendijk RW, Hop WC, et al. Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 2004; 240:578– 585 3. Bleichrodt RP, Simmermacher RK, van der Lei B, Schakenraad JM. Expanded polytetrafluoroethylene patch versus polypropylene mesh for the repair of contaminated defects of the abdominal wall. Surg Gynecol Obstet 1993; 176:18–24 4. Ramirez OM, Ruas E, Dellon AL. »Components separation« method for closure of abdominal-wall defects: an anatomic and clinical study. Plast Reconstr Surg 1990; 86:519–526 5. Bleichrodt RP, de Vries Reilingh TS, Malyar AW, et al. Component separation technique to repair large midline hernias. Op Tech Gen Surg 2004; 6:179–188 6. Maas SM, van Engeland M, Leeksma NG, Bleichrodt RP. A modification of the »components separation« technique for closure of abdominal wall defects in the presence of an enterostomy. J Am Coll Surg 1999; 189:138–140 7. Maas SM, de Vries Reilingh S, van Goor H, de Jong D, Bleichrodt RP. Endoscopically assisted »components separation technique« for the repair of complicated ventral hernias. J Am Coll Surg 2002; 194:388–390 8. de Vries Reilingh TS, Bodegom ME, van Goor H, et al. Autologous tissue repair of large abdominal wall defects. Br J Surg 2007; 94:791–803 9. de Vries Reilingh TS, van Goor H, Charbon J, et al. Repair of large midline abdominal wall hernias: components separation technique versus prosthetic repair. World J Surg 2007; 31:756–763 10. de Vries Reilingh TS, van Goor H, Rosman C, et al. »Components separation technique« for the repair of large abdominal wall hernias. J Am Coll Surg 2003; 196:32–37 11. Ewart CJ, Lankford AB, Gamboa MG. Successful closure of abdominal wall hernias using the components separation technique. Ann Plast Surg 2003; 50:269–273 12. Cohen M, Morales R Jr, Fildes J, Barrett J. Staged reconstruction after gunshot wounds to the abdomen. Plast Reconstr Surg 2001; 108:83–92 13. Jernigan TW, Fabian TC, Croce MA, et al. Staged management of giant abdominal wall defects: acute and longterm results. Ann Surg 2003; 238:349–355 14. Lowe JB III, Lowe JB, Baty JD, Garza JR. Risks associated with »components separation« for closure of complex abdominal wall defects. Plast Reconstr Surg 2003; 111:1276–1283

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15. Shestak KC, Edington HJ, Johnson RR. The separation of anatomic components technique for the reconstruction of massive midline abdominal wall defects: anatomy, surgical technique, applications, and limitations revisited. Plast Reconstr Surg 2000;105: 731–738 16. Szczerba SR, Dumanian GA. Definitive surgical treatment of infected or exposed ventral hernia mesh. Ann Surg 2003; 237:437–441 17. Vargo D. Component separation in the management of the difficult abdominal wall. Am J Surg 2004; 188:633– 637 18. DiBello JN Jr, Moore JH Jr. Sliding myofascial flap of the rectus abdominis muscles for the closure of recurrent ventral hernias. Plast Reconstr Surg 1996; 98:464–469 19. van Geffen HJ, Simmermacher RK, van Vroonhoven TJ, van derWerken C. Surgical treatment of large contaminated abdominal wall defects. J Am Coll Surg 2005; 201:206–212 20. Girotto JA, Chiaramonte M, Menon NG, et al. Recalcitrant abdominal wall hernias: long-term superiority of autologous tissue repair. Plast Reconstr Surg 2003; 112:106–114 21. de Vries Reilingh TS, Bleichrodt RP. Reply. World J Surg 2007; 31:2267–2268 22. Kingsnorth AN, Shahid MK, Valliattu AJ, et al. Open onlay mesh repair for major abdominal wall hernias with selective use of components separation and fibrin sealant. World J Surg 2008; 32(1):26–30

Discussion Franz: Can you tell us which mesh you are using in

this randomized study? Bleichrodt: We are using the Vypro II mesh be-

cause the study was running for a few years and that was the best mesh at that moment. So we had to go on with the same mesh; otherwise, we would have a problem comparing results. Deysine: Do you use antibiotic irrigation? Bleichrodt: We use antibiotic prophylaxis in every patient, and if the operation is longer than 3 hours, we give it again. Mostly we irrigate the wound with normal saline to remove, for example, blood clots and so on, but we don’t add antibacterials. We don’t have proof that it helps.

19

Conclusion of Session II, by J. Kukleta We had a quite extensive session, which can be divided into three parts: who gets the infection, how to treat the infection, and how to prevent the infection. To me, we got some take-home massages: We have to differentiate between wound infections and mesh infections and between acute mesh infections and late-onset mesh infections. We have heard interesting stuff about wound oxygen and its impact on wound healing. We have heard about biofilms and learned that it’s more difficult to fight against existing biofilms than to prevent them. But it still seems to be a complex part. The impregnation of mesh materials seems to be a good idea, but we have to learn more about that, probably with different materials. I want to close with the following remarks. Decreasing the infection rates by only 3% means thousands and thousands of people, so I would not talk about the price of €15 for antibiotics. This is our position in Switzerland. For any kind of implants, we use antibiotic prophylaxis.

III

III

Risk for Pain

20

Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair: A Reflection of Both Individual Pain Propensity and Surgical Strategy – 155

21

Chronic Pain After Inguinal Hernia Repair – 163

22

What Do We Know About the Pathophysiology and Pathology of Neuropathic Pain? – 169

23

Surgical Trauma of Nerves–Causes of Neuropathic Pain, Classification, and Options in Surgical Therapy – 177

24

Risks for Pain–Neuropathic Pain: How Should We Handle the Nerves? – 185

25

What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy – 191

26

Risk Factors for Chronic Pain After Groin Hernia Surgery – 199

27

Ischemic Inflammatory Response Syndrome as an Alternative Explanation for Postherniorrhaphy Pain – 207

28

Postoperative CRPS in Inguinal Hernia Patients – 213

29

Chronic Pain After Open Mesh Repair of Incisional Hernia – 221

30

Clinical Results After Open Mesh Repair – 227

31

Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair – 233

32

Effect of Nerve Identification on the Rate of Postoperative Chronic Pain Following Inguinal Hernia Surgery – 239

33

Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair: A Report from the SMIL Study Group – 245

34

Recurrence or Complication: The Lesser of Two Evils? A Review of Patient-Reported Outcomes from the VA Hernia Trial – 251

35

Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique – 257

36

The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia – 265

37

Lightweight Macroporous Mesh vs. Standard Polypropylene Mesh in Lichtenstein Hernioplasty – 275

38

Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain? – 279

39

New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia and Orchialgia – 287

40

Surgery for Chronic Inguinal Pain: Neurectomy, Mesh Explantation, or Both? – 293

41

Results of Tailored Therapy for Patients with Chronic Inguinal Pain – 299

20

Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair: A Reflection of Both Individual Pain Propensity and Surgical Strategy S. Smeds, L. Löfström, O. Eriksson, A. Kald

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Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

Introduction Discomfort from normal tissue healing after inguinal hernia surgery will have largely subsided at 3 months. Continued discomfort is referred to as postherniorrhaphy pain syndromes, which have diverse origins with peripheral neuropathic and nonneuropathic sources [1, 2]. In addition to the peripheral surgical trauma, pain perception is based on central nervous modulation of pain transmission. This may be influenced by age [3, 4] and other biological pain modulators [5, 6]. Expression of pain and discomfort may further be influenced by socioeconomic factors [7]. Finally, verbal eloquence and the ability to interpret assessment scales may influence final answers on self-assessment (SA) instruments. Thus, in addition to the variety of methods for inguinal herniorrhaphy, each inflicting a varying degree of peripheral tissue and nerve trauma, the variability of a number of biological and social factors possibly adds to variability in SA records. It was therefore deemed important to closely analyse the SA pattern 3 months after hernia repair. The clinic’s register gives further information on the preoperative self-assessed level of groin discomfort. This gives us an opportunity to study the degree of improvement (and impairment) following different types of repair at a point when a postoperative pain syndrome, by definition, starts.

Materials and Methods The Sergel Clinic is responsible for inguinal hernia surgery of all inhabitants in the central part of the county of Östergötland, Sweden, with a catch area of 228,000 inhabitants. The patient population covers all primary and recurrent groin hernias among elective patients older than 18 years of both genders and of American Society of Anesthesiologists (ASA) grades I–III. Since February 2004, preoperative and postoperative self-assessed levels of groin discomfort/pain have been recorded by intent by each patient.

20

Self-Assessment Instrument: Sergel Recovery Scale Self-assessment of preoperative groin problems was requested at patients’ first admission to the surgical clinic 1–4 weeks before surgery, and SA of postoperative discomfort related to the inguinal hernia repair was requested 3 months after the operation. The preoperative SA questionnaire was given before surgery in conjunction with the preoperative

⊡ Table 20.1. The lower part of column A represents the self-assessment (SA) levels (1–10) in the SA scale. The »preop« and »postop« columns give the number of patients in each SA level before and after the operation. Column B shows the number of patients whose preoperative to postoperative SAs changed by the number of steps indicated in column A. The maximum number of steps in the scale that can be registered is 9, i.e. from level 1 to level 10. This table is automatically updated when the quality follow-up database program is opened A

Preop

Postop

B

-9

0

-8

0

-7

0

-6

0

-5

1

-4

0

-3

1

-2

2

-1

5

0

29

1

36

0

49

2

55

2

65

3

112

1

63

4

82

2

68

5

69

4

75

6

72

9

81

7

50

19

74

8

53

65

33

9

43

134

29

10

10

363

SUM

582

599

575

157 Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

⊡ Table 20.2. Means and medians for preoperative and postoperative self-assessment (SA) 3 months after open hernia repair (level 10 denotes no discomfort). Fractions of patients rating themselves at level 8 and higher before and after surgery are indicated. The difference indicates the mean number of levels that the patients changed their rating from their preoperative to their postoperative SA Preop

Postop

Difference

Mean

4.877622

9.292020

4.397163

Median

5

10

5

Fraction>=8

18.2%

93.7%

an additional table showing the relative number of patients assessing themselves at levels 8–10 (⊡ Table 20.2). Those with postoperative SA at levels 7 and below were offered clinical follow-up. To analyse the validity of data collected from the primary answers, a second request for postoperative SA was sent 4–6 months after surgery to 55 patients who did not answer the first questionnaire. Analysis of difference by ordinal logistic regression showed no difference between the two groups (⊡ Fig. 20.2).

Primary and secondary self-assessment answers 10-log rel number of answers at each level

health report in the reception area, without contact with the surgeon. The postoperative SA questionnaire was given to the patient at the time of release from the clinic, with information to send it back 3 months later. The instrument consists of a visual 10-box scale in which SA level 10 represents no discomfort and level 1 represents the worst pain. A secretary routinely saved patients’ SA registrations into a database. When opened, the database automatically displayed updated information in a table, showing the number of patients at each level as registered before and 3 months after surgery as well as further numbers of patients who had moved an individually calculated number of steps in positive (improved) and negative (impaired) directions on the scale (⊡ Table 20.1). Furthermore, the updated preoperative and postoperative information was presented in two histograms (⊡ Fig. 20.1) and in

20

2

1.6

Primary answer N=599

1.2

y = 0.415x - 2.365 R 2 = 0.9906

0.8 Secondary answer N=55 y = 0.468x - 2.843 R 2 = 0.9119

0.4

0 1

2

3

4

5

6

7

8

9 10 11

Assessment levels

⊡ Fig. 20.2. Diagram demonstrating the similarity between the postoperative ratings from patients without reminders (primary answers, squares) and the ratings from patients after a reminder 1 month later (secondary answers, diamonds) at 4 months. The difference as analysed by logarithmic regression was not statistically significant. Data are presented as 10-logaritms of the relative number of patients at self-assessment levels 7–10

400 350 300 250 Preop

200

Postop

150 100 50 0 1

2

3

4

5

6

7

8

9

10

⊡ Fig. 20.1. Distribution of patients on the 10-level box scale in which 1 denotes the worst imaginable pain and 10 denotes no discomfort. White bars represent preoperative self-assessments 1–4 weeks before surgery (n=582), and black bars represent the postoperative rating 3 months after open hernia repair (n=599)

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Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

Patients

Statistical Methods

During the years 2004–2006, 1,439 hernias in 1,369 patients with unilateral and bilateral (8% of case series) inguinal hernias were operated upon. The operations were almost exclusively performed as day surgery under general anaesthesia. Anaesthesia was induced and maintained with propofol and remifentanil. Ventilation was controlled with a laryngeal mask. One surgeon performed 92% of the operations, and 10 consultants performed the additional 109 operations. Preoperative SA was obtained from all patients except for a few with mental disorders. All male, female (8.4%), and recurrent (6.1%) inguinal hernia patients were included in the register. The report is based on 562 patients who, without notice, returned their 3-month SA (41%). Missing data necessary for comparing preoperative and postoperative ratings were noted in 21 cases. Mesh procedures dominated in primary inguinal hernia surgery (77%). Single-plug procedures (12.8%) were restricted to small medial herniations with a well-defined hernia neck (low Spigeli herniation). A combination of plug and mesh was used in Nyhus IIIb hernias with large defects at the internal orifice and in large sliding hernias. In total, prostheses were used in 484 cases (89%). Suture reinforcement of the inner inguinal orifice (annulorraphy) with additional strengthening of the dorsal wall (11%) was used in young individuals, including fertile females, in whom sutures towards the inguinal ligament aligned with the strong internal oblique muscle. Calculations are based on 484 and 57 cases with prosthesis and suture repair, respectively.

Data are presented as means with standard deviation. For continuous data, Student’s t-test was used. Two-tailed probability of less than 5% (pvalue <0.05) was considered statistically significant. Differences in ordinal data in the 10-box SA scale were analysed with ordinal logistic regression (Minitab 15 software).

Results Self-Assessment in the Register Information Distributions of SA levels prior to surgery and 3 months after the operation are shown in ⊡ Fig. 20.1. At 1–4 weeks before surgery, the distribution of patients on the scale shows a peak at level 3 with a mean at level 4.9 (⊡ Table 20.2). Ten patients (1.7%) had no pain before surgery, and 36 (6.2%) registered the worst imaginable pain (⊡ Table 20.1). At 3 months after surgery, the mean SA level in the whole set of information was 9.3, and the mean number of improvement steps was 4.4 after the performed surgical procedures (⊡ Table 20.2). The distribution of improvement in the whole set of information is shown in ⊡ Table 20.1 and ⊡ Fig. 20.3. The majority of cases, 537 out of 575 (93.4%), changed in a positive direction on the SA scale. Twenty-nine patients (5%) had the same preoperative and postoperative SA level, mainly at levels 8–10. Nine cases were impaired (1.6%). The

n 90 80

20

⊡ Fig. 20.3. This diagram is based on column B in Table 20.1 and demonstrates the number of patients in relation to the number of steps in a positive or negative direction corresponding to the level of self-assessed improvement or impairment (-) between the preoperative and postoperative ratings. The y-axis shows the number of patients

70 60 50 40 30 20 10 0 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 Difference between pre- and postoperative SA

7

8

9

20

159 Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

relative number of patients who rated themselves without discomfort changed from 1.6% (n=10) preoperatively to 60.6% (n=363) postoperatively.

Improvement with Regard to Gender and Type of Repair

Only in sutured repair were no postoperative discomfort registrations below level 7 observed. In other subgroups–i.e. all unilateral and bilateral cases, all male and female cases, and prosthesis cases–assessments lower than 7 were found (⊡ Figs. 20.4 and 20.5).

There was no significant difference in mean improvement levels between suture and prosthesis repair, in male versus female patients, or in unilateral versus bilateral cases (⊡ Table 20.3). Bilateral suture repair (performed in men only) showed the lowest improvement, 2.83±2.13 steps on the scale, whereas the largest step was observed in unilateral suture repair, 4.76±2.50 (⊡ Table 20.3).

Postoperative SA Distribution Slope

35

350

30

The relationship between the number of patients and the degree of discomfort as reported at 3 months appeared to form a slope that might fit an exponential function (⊡ Fig. 20.6). To test this, the total number of cases at each SA level in the 10-box SA scale was transformed to a relative

300

Female patients

25

Male patients

250

20

Preop

200

Preop

15

Postop

150

Postop

10

100

5

50

0

0

1

2

3

4

5

6

7

8

9 10

1

2

3

4

5

6

7

8

9 10

⊡ Fig. 20.4. Distribution of preoperative and postoperative self-assessment among female and male patients. There was no difference as calculated with ordinal logistic regression, p=0.884

350

40 35

300

Suture repair

30

Prosthesis repair 250

25 20 15

Preop

200

Preop

Postop

150

Postop

10

100

5

50

0 1

2

3

4

5

6

7

8

9 10

0

1

2

3

4

5

6

7

8

9 10

⊡ Fig. 20.5. Distribution of preoperative and postoperative self-assessment after suture and prosthesis repair, respectively. There was no significant difference as calculated with ordinal logistic regression, p=0.099. Note the presence of cases in the lower part of the scale after prosthesis repair compared with suture repair, for which no postoperative registration lower than level 7 was found

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Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

⊡ Table 20.3. Mean (standard deviation, number) improvement steps in the 10-box self-assessment scale 3 months after open inguinal hernia surgery following suture or prosthetic repair, respectively. There was no significant difference between the improvement steps as calculated from the register data, nor between genders, nor between types of repair. Bilateral suture repair (in males only) showed the lowest mean improvement level, 2.83 steps, but showed no significant difference compared with unilateral suture repair, p=0.12, or bilateral prosthesis repair, p=0.19

Unilateral

Bilateral

Gender

Suture repair

Prostheses

Female

4.21±2.34 (n=24)

3.95±2.01 (n=23)

Male

4.76±2.50 (n=27)

4.43±2.60 (n=420)

Male

2.83±2.13 (n=6)

4.31±2.57 (n=41)

All inguinal hernia operations 2004-2006 390 363 340

Number of patients

290 240 190 140

134

90 65 40

⊡ Fig. 20.6. Number of patients at each self-assessment level on the 10level scale

1

All inguinal hernia operations 2004-2006 1.9

10-log rel number at each self assessment level

1.7 1.5

2

1 3

2

4

9

4 5 6 7 Self-assessment levels

19 8

9

10

number (percent) followed by calculation of the 10-logarithm of the relative number. The 10-logarithms were correlated to corresponding assessment levels in a diagram, and a straight line was formed, R2=0.9948 (⊡ Fig. 20.7).

1.3 1.1 0.9

y = 0.406x - 2.284 2 R = 0.9946

Discussion

2

Analyses of the register data create hypotheses rather than answering them. In contrast to randomised studies, however, they reflect the whole case mix. In routine clinical quality control on the basis of postal follow-up, only a fraction of the patients can be expected to return the first questionnaire. This is a weakness that can be defended only by a large number of cases and analysis of answers after a second request. Results of such analysis in the present paper indicate a close similarity between first and second answers. It can therefore be

0.7 0.5 0.3 0.1 -0.1 0

4

6

8

10

Self-assessment level

20

2

0

-10

⊡ Fig. 20.7. Relationship between 10-log of the relative number of cases in each self-assessment (SA) level and the corresponding SA level. A straight line with R2 =0.9948 indicates a strong correlation

161 Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

20

wards the surgical trauma. This variation among the surgical patients probably includes both varying inflammatory reaction to the surgical trauma and prostheses, when present, as well as genetically determined variation in sensitisation mechanisms [9]. The gender similarity indicates a common genetic variation of pain propensity between the sexes. There was no significant difference in the number of improvement steps after prostheses placement or suture hernia repair. This indicates that pain reaction to the surgical trauma seems to be a stronger pain determinant than the additional presence of a prosthesis. This is in concordance with previous observations in young males [10]. It was observed, however, that after suture repair, no patient indicated more discomfort than that associated with level 7 on the scale, in contrast to a number of patients receiving prostheses who rated themselves as having stronger pain. The number of cases with this important qualitative difference in their postoperative SA is probably too low to create a significant difference between the latter groups. Only a minor number of the 40% of patients who indicated some discomfort had a stronger pain reaction. Most of them indicated light discomfort at levels 9 and 8 at 3 months. One hypothesis raised after these observations is that the part of the scale that covers levels 7–10 may represent individual variation in sensitivity to the surgical trauma. The strict exponential distribution in the patient population of pain assessment in this part of the scale may support this interpretation. Patients with SA levels in the lower part of the scale,

assumed that the collected register data are representative for the register population. There was a distinct difference in the distribution of SA levels in the preoperative scale compared with postoperative ratings. The preoperative assessments were rather evenly distributed along the scale, with relatively low frequency at the extremes and with a more pronounced peak at level 3. The centre of the scale, level 5, divided the preoperative assessments into two equal parts. Only 10 out of 582 patients, 1.7%, reported no discomfort prior to surgery. This indicates that pain in addition to the inguinal herniation is a significant problem for the patient. In contrast, the postoperative ratings formed a linear-curve distribution along the scale. The slope was strictly fitted to an exponentially defined function, with approximately 60% of the cases reporting no discomfort, i.e. level 10 at 3 months. The remaining number of patients with slight discomfort to severe pain (approximately 40%) is similar to that observed in a Scottish study in which 43% had mild and 3% severe pain at 3 months [8]. The contrast between preoperative and postoperative SA levels (⊡ Fig. 20.8) reflects the wide variation of self-assessed discomfort/pain in a nonrandomised register group as compared with the intention-to-treat situation following a highly standardised surgical treatment. If one assumes only minute variations in surgical performance of the Lichtenstein repair as performed by one surgeon in several hundreds of patients, the observed SA slope in the scale may primarily be explained by individual variation in reaction patterns to-

Mean of postoperative selfassessment

10 9.8 9.6 9.4 9.2 9 8.8 8.6 8.4 1

2

3

4

5

6

7

Preoperative self-assessment

8

9

10

⊡ Fig. 20.8. Diagram demonstrating the gradual reduction in postoperative assessment of pain/discomfort (mean) in relation to preoperative selfassessment. Level 10 denotes no discomfort

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Chapter 20 · Self-Assessment of Discomfort and Pain after Inguinal Hernia Repair

levels 1– 6, additionally expressed the presence of a stronger pain component associated with the use of mesh or plug prostheses, as observed in the present register. To reach a closer understanding of these possibly diverse pain mechanisms, the variation of discomfort/pain must be analysed over a longer time frame.

References 1. Mikkelsen T, Werner MU, Lassen B, Kehlet H (2004) Pain and sensory dysfunction 6 to 12 months after inguinal herniotomy. Anesth Analg 99:146–151 2. Massaron S, Bona S, Fumagalli U, Battafarano F, Elmore U, Rosati R (2007) Analysis of post-surgical pain after inguinal hernia repair: a prospective study of 1,440 operations. Hernia 11:517–525 3. Ringkamp M, R Meyer (2006) Does peripheral sensitization of primary afferents play a role in neuropathic pain? In: Campbell JN, et al. (eds) Emerging strategies for the treatment of neuropathic pain. IASP Press, Seattle, pp 8–102 4. Matthews RD, Anthony T, Kim LT, Wang J, Fitzgibbons RJ Jr, Giobbie-Hurder A, Reda DJ, Itani KM, Neumayer LA; Veterans Affairs Cooperative 456 Studies Program Investigators (2007) Factors associated with postoperative complications and hernia recurrence for patients undergoing inguinal hernia repair: a report from the VA Cooperative Hernia Study Group. Am J Surg 194:611–617 5. Gordh T, Chu H, Sharma HS (2006) Spinal nerve lesion alters blood-spinal cord barrier function and activates astrocytes in the rat. Pain 124:211–221 6. Tegeder I, Costigan M, Griffin RS, et al. (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269–1277 7. Salcedo-Wasicek MC, Thirlby RC (1995) Postoperative course after inguinal herniorrhaphy. A case-controlled comparison of patients receiving workers’ compensation vs patients with commercial insurance. Arch Surg 130:29–32 8. Courtney CA, Duffy K, Serpell MG, O’Dwyer PJ (2002) Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 89:1310–1314 9. Tegeder I, Adolph J, Schmidt H, Woolf CJ, Geisslinger G, Lötsch J (2008) Reduced hyperalgesia in homozygous carriers of a GTP cyclohydrolase 1 haplotype. Eur J Pain 12:1069–1077 10. Bay-Nielsen M, Nilsson E, Nordin P, Kehlet H; Swedish Hernia Data Base; the Danish Hernia Data Base (2004) Chronic pain after open mesh and sutured repair of indirect inguinal hernia in young males. Br J Surg 91:1372–1376

20

Discussion Kehlet: You suggested that there was a difference

in pain compliance comparing mesh repair and suture repair. You may remember that we have collaboration between the Danish and Swedish Hernia Data base with a very detailed questionnaire that also compared young male who are at highest risk with Shouldice repair and Lichtenstein repair. And in 2000 patients there were no differences between this two techniques regarding chronic inguinal pain. Smeds: I think that there is no difference for the majority of patients. But in this database there were only a few patients who have had mesh repair. I think that in case of suture repair the patients have had comparable postoperative pain in general. Only some of them have had more pain, what may be related to a nerve lesion. Hopf: Have you investigated whether there is a difference regarding postoperative pain comparing local to general anesthesia? Did any of the patients get ketamin, because there are some data that suggested that patients who get ketamin are of high risk to develop postoperative pain. Smeds: All patients were operated using local anesthesia. And we never used ketamin in our patients. Schumpelick: In my opinion your main message is, that you have a relation of age and pain. Why is it so? Is it because of the nerve function? Is it the tolerance to pain? Is it experience of the patients? Smeds: We have to listen to those colleagues who are working on the problem of dorsal ganglion routes. May be there are mutations in the gene that processes the enzyme that forms the tetrahydrobiopterine. This is the first hint that there may be a genetically determined level of pain. I think that we will get much more information about the process of pain, and I think that it is individually different. However, I think that the preoperative pain score is very important to identify those patients who are of high risk of developing postoperative pain.

21

Chronic Pain After Inguinal Hernia Repair H. Kehlet, E. K. Aasvang

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Chapter 21 · Chronic Pain After Inguinal Hernia Repair

Introduction

Preop. pain intensity

21 There is now general agreement, based on data from randomised trials comparing different surgical techniques and larger amounts of epidemiological data, that chronic pain influencing daily activities may occur in 5–10% of patients [1–5]. Because little scientific data exist on evidence-based treatment of persistent postherniotomy pain, this undesirable outcome probably represents the most important one for improvement in groin hernia repair. The main focus for future research on the pathogenesis and treatment of chronic postherniotomy pain is the role of patient-related versus surgery-related factors [5] (⊡ Fig. 21.1). This report gives a short update on recent developments concerning the pathogenic mechanisms listed in ⊡ Fig. 21.1. Other factors such as age (decreased risk of chronic pain), female gender, and surgery for a recurrent hernia are other well-documented risk factors [3]; however, these cannot be altered.

Preoperative Pain The preoperative intensity of groin pain is a welldocumented risk factor for developing a persistent pain state [1, 3, 6] and corresponds to a similar documented risk following other surgeries [7]. Importantly, remote preoperative pain–i.e., pain in parts of the body other than the groin–has also been demonstrated to correlate with persistent pain, both in groin hernia repair [6, 8, 9] and other operations [7, 10]. These findings suggest that the preoperative functional level of the nociceptive system is an important risk factor, and several studies have shown a positive correlation between the pain response to a preoperative nociceptive stimulus (heat, electrical, cold) [7] and the acute postoperative pain response, which otherwise has been demonstrated to correlate with the risk of developing a persistent pain state [1, 7]. In summary, preoperative pain states and the level of nociceptive function are well documented as being important risk factors for developing a persistent pain state. They should therefore be included and assessed in all future pain trials, thereby providing possibilities for patient stratifi-

Genetics

Psyche

Acute postop. pain

Surgical trauma

Nerve injury

⊡ Fig. 21.1. Pathogenic mechanisms of persistent pain after groin hernia repair

cation into different risk groups when comparing different surgical techniques or pharmacological interventions.

Psychological Factors Preoperative anxiety and depression are wellknown characteristics of patients with chronic nonmalignant pain and have been demonstrated to be risk factors for acute pain states [7]. However, in pain after groin hernia repair, depression and anxiety were present in few (about 5%) patients [11] and may therefore not be considered important risk factors compared with other postsurgical persistent pain states in which malignancy, amputation, etc., may contribute to impaired psychosocial functioning. Nevertheless, preoperative assessment of anxiety and depression should be included in future high-level scientific studies on chronic postherniotomy pain.

Acute Postoperative Pain As mentioned above, in several operations, including groin hernia repair, a well-documented relationship exists between the intensity of the

165 Chapter 21 · Chronic Pain After Inguinal Hernia Repair

acute postoperative pain response and the risk of developing persistent pain [7]. For example, a large consecutive series with well-defined multimodal preemptive analgesia (including local anaesthesia, nonsteroidal anti-inflammatory drugs, and paracetamol) showed a threefold higher risk of chronic pain for patients with moderate to severe early postoperative pain compared to those with no or low-intensity acute postoperative pain [12]. Consequently, these and other findings [7] have led to the hypothesis that improved early postoperative pain treatment may reduce the risk of chronic pain (the concept of preemptive analgesia). However, so far the data are negative [7] and instead seem to suggest that the acute postoperative pain response is determined by the preoperative function of the nociceptive system, and thereby also the risk of persistent pain. Nevertheless, there is a need for further randomised studies, with more effective and prolonged acute pain treatment, on the risk of developing a persistent pain state.

Nerve Injury A main pathogenic mechanism for persistent postsurgical pain states is intraoperative nerve injury [7]. Obviously, with the three nerves passing the surgical field in groin hernia repair, there is a significant risk of nerve injury. Several studies have previously reported numbness after groin hernia repair; unfortunately, these reports did not use well-described, specific assessments of sensory disturbances as a sign of nerve injury, thereby limiting interpretation. This also includes studies comparing laparoscopic versus open repairs. A recent detailed study using the gold standard quantitative sensory assessment (QST) [11] in patients with and without persistent groin hernia pain, including patients who had bilateral repair, demonstrated that persistent postoperative sensory dysfunctions had a very low specificity for chronic pain, indicating that nerve damage occurs often, even in patients without chronic pain. However, signs of neuroplasticity with more frequent and intense pain after repetitive punctuate and brush stimulation were observed only in chronic pain patients

21

[11]. These findings confirm that nerve damage may be a prerequisite for developing a persistent pain state after groin hernia repair. However, corresponding to findings from other surgical procedures [7], factors other than nerve damage, including genetic factors, may contribute to persistent pain (see below). All future studies on persistent pain after groin hernia repair should include preoperative and postoperative detailed neurophysiological assessment in order to evaluate the relative importance of different pathogenic mechanisms. This is especially important for all studies comparing different surgical techniques such as laparoscopic versus open repairs, type of mesh, fixation techniques, and so on.

Surgical Trauma As mentioned above, surgical injury to one or all of the three groin nerves may occur frequently, although all efforts should be made to identify and preserve these nerves, as discussed in other chapters in this book. Consequently, the surgical technique may be important for preventing or reducing a persistent pain state. However, so far the literature is not entirely conclusive regarding laparoscopic versus open repair, type of mesh (composition, lightweight versus heavyweight), and different fixation techniques. One reason may be that for each of these topics the other variables have not been well described, which especially applies to studies comparing laparoscopic and open repairs. Ideally, the risk of nerve injury should be reduced in laparoscopic repair without mesh fixation–but most reports have insufficiently described the fixation technique and its risk in terms of nerve injury. Prospective ongoing studies that include all risk factors (preoperative, intraoperative, and postoperative) in collaboration with Copenhagen and Stuttgart and with detailed QST assessments have completed patient inclusion and 6 months of follow-up. It is hoped that the data will be able to clarify the effects of high-expertise laparoscopic repair without mesh fixation versus high-expertise open Lichtenstein repair.

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Chapter 21 · Chronic Pain After Inguinal Hernia Repair

In summary, there is no doubt that the surgical technique is important for avoiding the risk of nerve damage, especially when mesh may cause compression of the nerves [13, 14]. Future trials are called for, and they need to include high-quality assessment of the signs of nerve damage when comparing different techniques.

Genetic Factors Based on the findings from a variety of surgical procedures, only a fraction of patients with documented intraoperative nerve injury develop a persistent pain state [7, 11]. Recent studies with genotype characterisation have suggested that COMT genes are important for pain sensitivity [15] and that GTP-cyclohydrolase regulates pain sensitivity in normal subjects and pain-related outcomes after spinal surgery [16]. Genes controlling the function of the voltage-gated sodium channel are also important [15]. Although this is a developing field of pain research, all future high-level scientific studies on persistent groin hernia pain should include characterisation of the genetic architecture of pain perception to provide further understanding of the mechanisms and risk factors for persistent groin hernia pain. Unfortunately, no data are available so far.

Summary The pathogenic mechanisms of chronic pain after groin hernia repair are definitely of multifactorial origin [5], and previous efforts to classify the syndromes into neuropathic versus nonneuropathic (inflammatory) pain [17] may not be founded on clear-cut diagnostic criteria. Thus, nerve injury after groin hernia repair occurs very frequently but leads to a chronic pain state in only a fraction of patients. However, since nerve injury seems to be a prerequisite for developing persistent pain, all efforts should be made to develop and characterise surgical techniques to avoid peripheral nerve injury. It is hoped that future studies will include a complete characterisation of all pathogenic mechanisms–something that has not happened before

in the large number of studies with chronic pain as an outcome [5]. Such characterisation must also be included in future trials on pharmacological treatment [7] as well as in studies on surgical treatment with neurectomy and mesh removal [14] and where preliminary data with detailed neurophysiological characterisation and functional outcomes suggest such techniques to reduce chronic pain in some, but not all, patients [18].

References 1. Aasvang E, Kehlet H. Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 2005; 95:69–76 2. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewoud H, Bleichrodt R. Chronic pain after mesh repair of inguinal hernia: a systematic review. Am J Surg 2007; 194:394–400 3. Franneby U, Sandblom G, Nordin P, Nyren O, Gunnarsson U. Risk factors for long-term pain after hernia surgery. Ann Surg 2006; 244:212–219 4. Ferzli GS, Edwards E, Al-Khoury G, Hardin R. Postherniorrhaphy groin pain and how to avoid it. Surg Clin North Am 2008; 88:203–209 5. Kehlet H. Chronic pain after groin hernia repair. Br J Surg 2008; 95:135–136 6. Wright D, Paterson C, Scott N, Hair A, O’Dwyer PJ. Fiveyear follow-up of patients undergoing laparoscopic or open groin hernia repair: a randomized controlled trial. Ann Surg 2002; 235:333–337 7. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006; 367:1618–1625 8. Courtney CA, Duffy K, Serpell MG, O’Dwyer PJ. Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 2002; 89:1310–1314 9. Aasvang EK, Mohl B, Bay-Nielsen M, Kehlet H. Pain related sexual dysfunction after inguinal herniorrhaphy. Pain 2006; 122:258–263 10. Brandsborg B, Nikolajsen L, Hansen CT, Kehlet H, Jensen TS. Risk factors for chronic pain after hysterectomy: a nationwide questionnaire and database study. Anesthesiology 2007; 106:1003–1012 11. Aasvang EK, Brandsborg B, Christensen B, Jensen TS, Kehlet H. Neurophysiological characterization of postherniotomy pain. Pain 2008; 137:173–181 12. Callesen T, Bech K, Kehlet H. Prospective study of chronic pain after groin hernia repair. Br J Surg 1999;86: 1528– 1531 13. Demirer S, Kepenekci I, Evirgen O, Birsen O, Tuzuner A, Karahuseyinoglu S, Ozban M, Kuterdem E. The effect of polypropylene mesh on ilioinguinal nerve in open mesh repair of groin hernia. J Surg Res 2006; 131:175–181 14. Amid PK, Hiatt JR. New understanding of the causes and surgical treatment of postherniorrhaphy inguinodynia and orchalgia. J Am Coll Surg 2007; 205:381–385

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15. Diatchenko L, Nackley AG, Tchivileva IE, Shabalina SA, Maixner W. Genetic architecture of human pain perception. Trends Genet 2007; 23:605–613 16. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006; 12:1269–1277 17. Loos MJ, Roumen RM, Scheltinga MR. Classifying postherniorrhaphy pain syndromes following elective inguinal hernia repair. World J Surg 2007; 31:1760–1765 18. Aasvang EK, Kehlet H. The effect of mesh removal and selective neurectomy on persistent postherniotomy pain. Ann Surg 2009; 249:327–334

Discussion Deysine: Within the population that I operated

there were a lot of young people for instance teenagers. Within this population there was a lot incidence of drug intake before surgery. In my opinion this is an important factor in developing postoperative pain. Did you consider such things in your study? Kehlet: We know that the management of acute pain is very difficult in such patients. However, I have never seen such a problem of drug addiction in patients operated because of an inguinal hernia. We don´t have such patients in Denmark, but I think that this could be a risk factor as well. Schumpelick: Could you give us some more remarks about »pain genes«. This seems to be a very new story and we want to know a little bit more about that. Kehlet: I showed you the references of the two best candidates that may be important »pain genes«. In mouse and rat studies there were a lot of more possible candidate genes. But the two mentioned genes are the only genes that were also found to be of interest in humans. One of it was found in factory workers who were analyzed for chronic mandibular pain. And after some years they could predict those who are of risk to develop this chronic pain syndrome. But what we have to do in the future is to combine all the different characteristics of all »pain genes«. At the moment we were at an early stage we have not enough information that it would be relevant for clinical praxis.

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O’Dwyer: Any statements regarding the fact that

every patient with chronic pain has some sort of sensory deficit? What is your experience with testicular pain, because 15% of our patients develop specific testicular pain? Kehlet: Specific testicular pain is quite rare. But we have not analyzed it in the current study. However, we have to do this statistical comparison, because we included all this data in our data base. Song-Zhang Ma: Chronic pain is a severe problem. In China inguinal hernia repair using mesh materials is performed 150.000 times per year. But so far I have just a very few reports on postoperative pain. What do you think is the reason? Is this because of the tolerance of pain? Kehlet: There could be several explanations. One could be that patients in China have a different genetic profile. Another reason could be that you really have not asked your patients about discomfort and postoperative pain. We have had this hernia meeting several times before, and we have never talked about chronic postoperative pain. We didn’t talk about it because we didn´t realized such problems. Song-Zhang Ma: I totally agree. Before the operation we talk about recurrence and infection, but we didn’t talk about chronic postoperative pain in detail. Amid: Few patients following inguinal hernia repair develop specific testicular pain. We did an investigation that this problem could be related to the fact that the nerves were involved in the lamina propria of the vas deference. We have just 12 cases, therefore it is not enough to make a conclusion, but it is a very significant finding. Kehlet: I agree. Schumpelick: Is there a correlation between income and development of postoperative pain? Kehlet: There are many factors to consider, however actually I cannot comment on this. But this is the reason why we should have a detailed characterization of our patients.

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What Do We Know About the Pathophysiology and Pathology of Neuropathic Pain? P. L. Jansen, K. Bas, D. Kämmer

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Introduction

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After hernia surgery, severe chronic pain is reported in up to 10% of the patients. The treatment of these patients using neurectomy, mesh explantation, and symptom control by administration of analgesics frequently fails and hints at a neuropathic pain syndrome, at least in a subgroup of patients. Neuropathic pain syndromes are caused by irreversible changes of the nervous system. For postoperative neuropathic pain, inflammation as well as nerve degeneration and pathological regeneration are the underlying pathological mechanisms that precede these central nervous changes. Advances in understanding the peripheral pathophysiological mechanisms are necessary to develop sufficient tools for preventing and treating neuropathic pain. A pathophysiological reclassification could provide a new basis for targeted and individualized therapy of patients with chronic pain after hernia therapy.

Neuropathic Pain Neuropathic pain is defined as chronic, not selflimiting pain that can occur after any lesion or dysfunction of the peripheral or central nervous system. In contrast to nociceptive and inflammatory pain, neuropathic pain has no protective function and arises by inadequate stimulation of the peripheral sensory endings [1]. Etiology-based classifications of painful peripheral neuropathies include syndromes caused by generalized lesions of the peripheral nervous system (e.g., polyneuropathies), complex neuropathic disorders (e.g., complex regional pain syndromes), and syndromes caused by focal or multifocal lesions of peripheral nerves (e.g., postsurgical pain syndromes) [2]. Based on this definition, we can expect neuropathic pain after any surgical intervention, at least in a subgroup of patients, and even when the operating field is in close proximity to peripheral nerves. Indeed, we can observe neuropathic pain syndromes after Shouldice, Lichtenstein, and even laparoscopic hernia repair [3]. Neuropathic pain has to be clearly separated from chronic pain caused by neuroma formation following nerve injury or affec-

tion of nerves due to mesh-induced foreign body reaction. For the latter, surgical intervention can be successful. In contrast, neuropathic pain is associated with irreversible neuronal changes; therefore, surgical treatment by neurectomy or mesh explantation may be insufficient [4].

Pathophysiology of Neuropathic Pain Inflammation, degeneration of nerve fibers, reparatory mechanisms of neural tissue, and the reaction of the connective tissue lead to hyperexcitability in primary afferent nociceptors [2]. The hyperactivity in nociceptors that is called peripheral sensitization induces secondary changes in processing neurons in the spinal cord and brain that amplify the state of hyperexcitability and lead to central sensitization. Normally, these sensitization phenomena are limited until the tissue heals and the inflammation subsides. However, when primary afferent function is altered permanently, the state of hyperexcitability persists (⊡ Fig. 22.1). The resulting clinical signs are the spontaneous pain, allodynia, and hyperalgesia that are characteristic for patients with neuropathic pain. A simple focal peripheral nerve injury causes a variety of changes in the nervous system, which can all contribute to the persistence of pain and abnormal sensation. We can observe changes in the peripheral primary afferent neurons as well as in the central nervous system. These changes include upregulation of sodium channels and specific receptors as well as synthesis and secretion of cytokines and neurotransmitters, leading to ectopic impulse generation, reduced activation threshold, or increased synaptic transmission. At the central nervous system, the loss of intraspinal inhibition due to the death of inhibitory interneurons plays a crucial role [2, 5]. These neuronal changes are independent from the underlying disease, and the same neuronal mechanisms are responsible for neuropathic pain after hernia repair as for other pain syndromes. Because several mechanisms can cause a specific pain symptom, a combined therapy is often more promising than a single one. Peripheral and central neuronal changes are the common track for neu-

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⊡ Fig. 22.1. Pathophysiology of neuropathic pain (BMI body mass index)

ropathic pain syndromes, but pathophysiological changes at the site of peripheral nerve injury precede these neuronal changes.

Inflammation in Neuropathic Pain Recent publications hint at a pivotal role of the inflammatory reaction for the development of neuropathic pain. After tissue injury, mast cells, macrophages, T-cells, neutrophils, and Schwann cells are activated and infiltrate from endoneural blood vessels into the nerve (⊡ Fig. 22.2) [6]. They secrete huge amounts of cytokines, nerve growth factors, and proteases. These mediators induce ectopic activity via receptor-mediated actions on afferent nerve fibers. Although the impact of nerve inflammation on neuronal changes has not been clarified in detail, it is known that the inflammatory reaction after nerve injury initiates and maintains sensory abnormalities [2, 6]. Macrophages are key cells after nerve injury. Barclay et al. found that the depletion of macrophages attenuates the mechanical hyperalgesia after peripheral nerve lesions in rats [7]. In a

preliminary study, we investigated a potential role of macrophages for neuropathic pain in hernia patients. In contrast to healthy nerves obtained from pigs, infiltrating macrophages were frequently detected in neurectomy specimens from hernia patients with chronic pain (⊡ Fig. 22.2). The expression of matrix metalloproteinase 2 (MMP-2), a pivotal mediator of macrophages, is also enhanced, especially in the endoneurium. A role of MMPs in the development of neuropathic pain after spinal nerve ligation was demonstrated recently in rats and mice by Kawasaki et al. [8]. MMP-9 showed rapid upregulation in injured dorsal route ganglions, whereas MMP-2 was responsible for the late phase of neuropathic pain and was upregulated in primary afferent neurons as well as in the dorsal horn. This study demonstrated for the first time that peripheral processes do not occur in isolation from central neuroinflammation. The separation between early-phase and late-phase neuropathic pain mechanisms can lead to important clinical implications, such as the development of tools for preventing and treating neuropathic pain. Kawasaki et al. [8] demonstrated that the develop-

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⊡ Fig. 22.2. Immunohistochemistry of CD68 (macrophages) and MMP-2 in ilioinguinal nerve specimens from pigs and chronic pain patients after hernia therapy. Magnification ×200

ment of pain hypersensitivity could be inhibited by the administration of MMP inhibitors and small interfering RNA in MMP knockout mice. Interestingly, a role of MMP-2 is also well known to support mesh-induced chronic foreign body reaction. Mesh implantation in animal models induces excessive MMP-2 gene transcription and activity mediated by infiltrating macrophages, and this pathway may also contribute to the development of neuropathic pain.

The Role of Fibrosis in Neuropathic Pain Next to the inflammatory reaction, nerve injury activates Schwann cells and fibroblasts. These cells synthesize fibronectin and, later on, collagens and are responsible for changes in the extracellular matrix. The common understanding is that the fibrotic reaction around the nerve can affect nerve fibers and lead to the retraction or compression of

nerves by compromising proper function of this so-called perineurium. Additionally, the fibrotic reaction can lead to obliteration of Schwann cell tubes and block axon regeneration or lead to missprouting of axons, resulting in the formation of neuromas at the end of injured nerve fibers or even intraneurally. The extraneural conditions can be successfully treated by surgical intervention. In contrast, the composition of the endoneurium can be disturbed after nerve injury. Salonen et al. analyzed the fibrotic reaction after sciatic nerve transaction in rats. They found increased expression of fibronectin and collagens, especially type III collagen in the endoneurium [9]. Similarly, we could detect a distinct expression of type I and type III in nerve specimens from chronic pain patients (⊡ Fig. 22.3). Although the impact of a disturbed endoneuronal collagen expression on neuronal changes is not yet clarified, these changes may be involved in the induction of ectopic activity of injured primary afferent nociceptors as well as of spared fibers.

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⊡ Fig. 22.3. Endoneural distribution of type I collagen (red) and type III collagen (green) in neurectomy specimens of chronic pain patients after hernia therapy. Sirius red staining, magnification ×200

Furthermore, our preliminary data hint at an individual reaction to nerve injury.

The Impact of Risk Factors on Neuropathic Pain In some but not all patients, the nerve lesion triggers molecular changes in nociceptive neurons, which become abnormally sensitive and develop pathological spontaneous activity. Several studies have shown that individual risk factors have an impact on the development of neuropathic pain. Major risk factors are age younger than 40 years, preexisting preoperative pain, severe postoperative pain, and male gender [10–14]. We confirmed these results in patients who had mesh explantation either because of chronic pain or reoperation for hernia recurrence. In our cohort, we found that age under 50 and body mass index less than 25 were significantly associated with chronic pain. To determine the tissue reaction in these two groups, we further analyzed the inflammatory reaction and found that the young patients who were at risk for developing chronic pain had significantly enhanced infiltration of macrophages after mesh implantation compared with older patients.

Summary and Outlook Inflammation, fibrosis, and neuronal regeneration can lead to complex changes in the function, chemistry, and structure of neurons and glial cells. These mechanisms are independent from the underlying disease and can occur after any surgical intervention, even after hernia therapy. Patientrelated risk factors can be additional disturbing factors in the complex system of pain perception. Though major progress has been made in the understanding of cellular and molecular changes after nerve injury, their relevance for the pathophysiology of pain in neuropathies after hernia therapy has yet to be determined. A mechanism-based approach for treating neuropathic pain provides hope for safer and more specific therapies.

References 1. Treede R-D, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J: Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008, 70:1630– 1635 2. Baron R: Mechanisms of disease: neuropathic pain–a clinical perspective. Nat Clin Pract Neurol 2006, 2:95–106

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3. Franneby U, Sandblom G, Nordin P, Nyren O, Gunnarsson U: Risk factors for long-term pain after hernia surgery. Ann Surg 2006, 244:212–219 4. Kehlet H: Chronic pain after groin hernia repair. Br J Surg 2008, 95:135–136 5. Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999, 353:1959–1964 6. Thacker MA, Clark AK, Marchand F, McMahon SB: Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg 2007, 105:838–847 7. Barclay J, Clark AK, Ganju P, Gentry C, Patel S, Wotherspoon G, Buxton F, Song C, Ullah J, Winter J, Fox A, Bevan S, Malcangio M: Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain 2007, 130:225–234 8. Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, Gao YJ, Roy K, Corfas G, Lo EH, Ji RR: Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med 2008, 14:331–336 9. Salonen V, Lehto M, Vaheri A, Aro H, Peltonen J: Endoneurial fibrosis following nerve transection. An immunohistological study of collagen types and fibronectin in the rat. Acta Neuropathol 1985, 67:315–321 10. Kehlet H, Jensen TS, Woolf CJ: Persistent postsurgical pain: risk factors and prevention. Lancet 367:1618–1625 11. Aasvang E, Kehlet H: Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 2005, 95:69–76 12. Matthews RD, Anthony T, Kim LT, Wang J, Fitzgibbons Jr RJ, Giobbie-Hurder A, Reda DJ, Itani KMF, Neumayer LA: Factors associated with postoperative complications and hernia recurrence for patients undergoing inguinal hernia repair: a report from the VA Cooperative Hernia Study Group. Am J Surg 2007, 194:611–617 13. Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA: A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 2003, 19:48–54 14. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewoud H, Bleichrodt R: Chronic pain after mesh repair of inguinal hernia: a systematic review. Am J Surg 2007, 194:394– 400

Discussion Penkert: Do you agree that we have no data that

a certain number of patients develop neuropathic pain? And please comment on what has been mentioned before: Influences the kind of preoperative drug medication – especially morphium like medicaments – the incidence of chronic postoperative pain following groin hernia repair? Lynen-Jansen: I totally agree. In the literature concerning the pathophysiology of neuropathic pain, the authors focus on just one special mechanism.

They focus on fibrosis, they focus on inflammation or they focus on neuronal changes. Unfortunately I have no personal experience of preoperative drug medication and the development of postoperative pain. Deysine: You mentioned that there were pathologically changes in nerves occurring at this kind of surgery. But this would mean that the surgeon physically contacts the nerves. Neurosurgeons particularly touch nerves just with glass-electrodes. And we retract nerves while the operation and touch them with metal instruments. In my opinion the physical contact to the nerves has to be avoided. Lynen-Jansen: I totally agree. But I also think it is a lucky situation if you can avoid contact to a nerve physically. But injury to the nerves are also possible by stretching them, especially if you don´t see them while the operation. Kehlet: What you mentioned about continuous development of chronic pain is in contrast to what we have published. In our studies the pain incidence increases. We have very few prospective data concerning chronic pain however can you comment on your different findings. Lynen-Jansen: In my opinion these were only data in case of mesh implantation. Additionally it was a retrospective study and therefore it was not so easy to determine the time point when the pain occured exactly for the first time. Köckerling: In case of a patient in later course after an endoscopic hernia repair, you have to watch carefully for a recurrence or another morphological reason for the pain. I have never seen a patient with chronic pain without a morphological cause of chronic pain. Lynen-Jansen: I totally agree, again this study has its natural limitations because it was a retrospective study. Smeds: Do you have any biological data that would explain the correlation between pain and age? Lynen-Jansen: At the moment we just have the preliminary immunohistochemical investigations and therefore no satisfying answer for your question. But we have some data that the inflammatory reaction in young patients is different compared to elder patients. A lot of biological reactions in younger people are more aggressive, even the in-

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flammatory reaction. But the main question is, why do some young patients develop postoperative chronic pain and why other not. The answer could be that we have a multifactorial impaired disease. Stumpf: I want to comment on your immunohistochemical data and on what Dr. Deysine said. It is not a problem of how to handle the nerve, because we did this investigation in nerves that we have never touched before explanation. We explanted the nerves in case of retroperitoneal neurectomies. In my opinion it is rather a preexisting disorder than a consequence of a physical never contact. Schumpelick: Are there any differences comparing the two groups in getting a recurrence of developing postoperative chronic pain? Lynen-Jansen: In case of the explanted mesh material we saw significant differences in the infiltration of macrophages in patients with chronic pain. Franz: If you exclude the patients with a recurrence, where did you get the nerves from in the pain free patients? Lynen-Jansen: The two mentioned studies were completely different.

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Surgical Trauma of Nerves–Causes of Neuropathic Pain, Classification, and Options in Surgical Therapy G. Penkert

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Chapter 23 · Surgical Trauma of Nerves–Causes of Neuropathic Pain, Classification, and Options in Surgical Therapy

Introduction

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With the introduction of microsurgical methods applied to peripheral nerve lesions such as entrapment syndromes, pseudoneuroma, and neuroma formations, as well as lesions with nerve discontinuity, the results of nerve surgery have significantly improved over the last three to four decades. But no real mental connection exists between these successful microsurgical methods for improving or even restoring nerve function and theories of the origin of neuropathic pain. This type of hardly treatable and, until now, not fully explained pain often causes complete social disintegration of the patient. By means and results of microsurgery, we were encouraged to apply these surgical improvements to pain related to nerve trauma, but we faced limitations that were difficult to overcome until today. Experiences in neuromodulation continue to offer new aspects, and quite recent reports on intraabdominal laparoscopic neuromodulation even seem to offer a solution to painful pelvic nerves.

Microscopic Anatomy of the Peripheral Nerve System We regard the nerve axon as the smallest anatomical unit. The myelin sheath and its Swann cells are located around the axon membrane. These structures are enclosed in two or more layers: one layer with latticed and the other with longitudinal collagen and elastic fiber elements–the endoneurium. A certain number of such nerve fibers together with their individual endoneural sheath are again surrounded by connective tissue– the perineurium. Again, a certain number of such bundles (fascicles) are grouped parallel to each other, and they are again surrounded by connective tissue–the epineurium. This group arrangement within peripheral nerves changes its distribution from central levels to the periphery. Additionally, individual crossconnections between these fascicles and groups of fascicles exist. Nerve roots consist of few but thicker fascicles divided into sectors by small membranes, whereas in the periphery, limb nerve

segments have a typical group arrangement with three to five or more groups of fascicles. Closer and closer to the periphery, these groups further subdivide into many small single fascicles. This special multifascicular structure is the one we also find within the often painful inguinal nerves, including the iliohypogastric, ilioinguinal, and genitofemoral nerves. Following nerve damage or even transection, all of the elements constituting the nerve fiber, axon, and myelin sheath degenerate from the level of the lesion to the periphery. Our surgical efforts now normally aim at establishing the best conditions as possible so that these axons can sprout again into the periphery and achieve their former targets. Unfortunately, reconstructions of those multifascicular and small nerves have tended to result in secondary neuromas at the coaptation sites; the reason was aberration of all the small fascicles at the coaptation site because of technical difficulties despite magnification under the microscope.

Types and Degrees of Nerve Lesions As the result of destructive effects on nerve tissue, we can distinguish between lesions with and without loss of continuity. In almost all cases, the question of continuity of the involved nerve remains unanswered. Two systems were therefore developed to describe the potential degrees of nerve tissue lesion. In 1943, Seddon established the concepts of neurapraxia, axonotmesis, and neurotmesis according to the degree of destructive forces on the nerve tissue [18]. Neurapraxia refers to myelin sheath degeneration within the affected nerve segment. Axonotmesis is defined as a complete interruption of the axon’s continuity. Neurotmesis, in contrast to the other types of lesion, means a complete nerve interruption. Cases of neurapraxia recover within a few weeks if the forces that compress the nerve are removed. Cases of axonotmesis recover within several months depending on the distance between lesion and target. Cases of neurotmesis cannot recover, and the targets remain paralyzed. But the prognosis of axonotmesis cases depends on additional factors. In light of this, in

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1951 Sunderland distinguished five degrees of lesion [20]. Today we consider his classification to be more detailed and more suitable than Seddon’s earlier one: Grade 1: This grade is identical to Seddon’s neurapraxia, and it refers to myelin sheath degeneration restricted on a nerve segment due to a slight trauma. Grade 2: As a result of higher compressing forces, the axons undergo Wallerian degeneration, but each axon remains enclosed by its basal membrane and endoneurium, and it is able, by axon sprouting, to regain its former target. Grade 3: Because of destructive forces on the endoneurium, the process of axon resprouting is partially hindered. On the other hand, mis-sprouting leads to more extensive functional deficits: Without endoneurium, motor axons may sprout into a sensory pathway, or vice versa, and thus achieve no function. Grade 4: Because of disarranged perineurium, the amount of mis-sprouting increases so extensively that the recovery results after microneurolysis are even more disappointing than with grades 2 and 3 lesions. Especially in cases of small skin nerves as well as inguinal nerves, the intraneural destructive effects are easily able to completely block the axon sprouts, a situation that results in a neuroma in continuity. This kind of lesion is comparable to a total nerve interruption, with no good prognosis as far as spontaneous recovery is concerned. Grade 5: This lesion is identical to Seddon’s neurotmesis, a complete interruption of nerve trunk continuity. It is associated with a terminal neuroma at the proximal nerve stump 6–8 weeks after the nerve trauma.

Secondary Connective Tissue Reactions Following a nerve injury, not only nerve destruction but also secondary connective tissue reactions start; histologically, these are well-known processes referred to as fibrosis. The ensuing scar tissue develops compressing forces and blocks the axon-sprouting process. Considering all of these secondary effects, in 1992 Millesi established a

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classification of different fibrosis types [8]. It was conceived from a surgical point of view, as Millesi noted that the fibrosis could originate from quite different parts of the connective tissue within nerves. He classified fibrosis into types A–C, regarding the fact that only the epineurium, or the interfascicular connective tissue, or even the intrafascicular connective tissue (the endoneurium) could be involved in the fibrosis. This differentiation became important because, due to this fibrosis, surgical limitations arise during microneurolysis. An epineural fibrosis can be easily released by a longitudinal incision. In contrast, an endoneural fibrosis limits our surgical efforts completely. Nerve segments with intrafascicular fibrosis have to be resected and reconstructed by grafting. Consequently, the surgeon’s task during each operation is to estimate the type of fibrosis and decide which microsurgical method is suitable [13].

Microsurgical Options In general, we distinguish between neurolysis and nerve reconstruction, with the latter consisting of either direct nerve suture or nerve grafting. Both techniques today require a microscope to guarantee gentle handling of the nerve tissue. With magnification, the epineurium in intact parts of the nerve proximal and distal to the injured area can be incised longitudinally. After that, the external sheath of the epineurium can be removed. As a next step, individual groups of fascicles are exposed and slightly separated from each other. When approaching the injured nerve segment, the surgeon should try to continue; if that is not possible, he or she has to switch over to repair. But at first, at the separated fascicle groups, the surgeon should try to incise the perineurium if scarred. These microneurolysis steps are referred to as epineurotomy, epineurectomy, and interfascicular neurolysis. These different surgical steps can be applied to limb nerves of sufficient caliber; however, the smaller in diameter the nerve is and the more multifascicular, the greater the number of limitations that will arise, particularly in cases of skin nerves and inguinal nerves.

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Nerves with loss of continuity or untreatable intraneural fibrosis should be reconstructed if possible. The approach to nerve repair that must be implemented for these lesions changed in the 1960s [9]. The former nerve repair techniques involved the epineural end-to-end suture, but histological studies showed that fibrosis and neuromas developed on the suture side [3]. The development of microsurgical grafting resulted in two advantages: A more accurate approximation of corresponding fascicles could be achieved [8, 16], and restoration of nerve continuity without tension significantly reduced the amount of fibrosis at the coaptation sites [10]. Despite the fact that the axons had to overcome two coaptation sites after grafting, the end results 40 years ago were so encouraging that grafting became the method of choice from then on [9]. In the meantime, all of the mentioned principles of microsurgery became well known.

Pain Associated with Nerve Lesions In former decades, nerve surgeons were convinced that these microsurgical principles could successfully be applied to pain related to nerve injury. They believed that removal of the neuroma had to be the solution in pain relief; resprouting of sensory axons would sufficiently help nociceptive afferents become stabilized by achieving their former targets. But this concept did not reliably work. In 1981, a study on this subject described the high failure rate of nerve resection and grafting to cure the associated chronic nerve-related pain [12]. All of the patients reported in this study underwent reconstruction of the injured and painful nerve segment by grafting of the sural nerve. Although motor or sensory nerve function was successfully restored in all seven patients, their pain returned in the precise state and location as experienced preoperatively. Today, mechanisms proximal to the nerve lesion are recognized as responsible for the recurrence of nerve-related pain, and we are even aware of the risk of duplicating the pain [23]. Entrapment syndromes of limb nerves usually cause a more or less bearable pain. The pain does not remain restricted to the autonomous distribu-

tion area of the affected nerve; rather, it is diffuse, and it disappears after nerve decompression [13]. This type of nerve-trunk-related pain is not a matter of discussion because a substantial intraneural nerve lesion usually does not arise in an entrapment situation. Instead, we have to deal with nerves that (1) are small in diameter, (2) predominantly contain sensory fibers, (3) easily react with intraneural severe fibrosis, and (4) additionally limit our microsurgical efforts while often being unfavorably localized. In particular, these nerves tend to develop intractable pain, and we need to strictly avoid attaching the label »psychologically peculiar« to persons with resistant pain of those nerves. We are thus confronted with three potential levels of pain: 1. Neuroma pain, a normally nonexistent pain that occurs when triggered by palpation at the location where sensory nerve fibers are blocked from regrowing. Palpation thereby causes an electric-current-like pain that the patient localizes in the distribution area of the injured nerve. 2. Hyperpathic pain, a normally nonexistent pain of unbearable intensity if the skin in the distribution area of the injured nerve is repeatedly stimulated 3. Allodynia, a pain that is permanently present as a burning sensation and that is triggered by an innocuous stimulus Both of the last two types of pain are also referred to as neuropathic pain. Neuroma pain appears about 6 weeks following the nerve lesion because a neuroma needs this time to develop. Consequently, neuroma pain starts slowly and achieves a steady state weeks later. In contrast, neuropathic pain (1) has a sudden onset, (2) appears rather early after the nerve lesion, and (3) immediately achieves a steady state. Therefore, it is very important to evaluate all the details of the patient’s anamnesis to estimate his or her individual type of pain. It may be of additional importance to assess the patient because in the case of allodynia, you should be able to apply a quite light stimulus to a small skin area to provoke

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a highly painful sensation that spreads away from the actual stimulus location. This special attribute, by the way, may be the reason that we sometimes cannot exactly differentiate which one of the inguinal nerves is really affected. Unfortunately, the distribution areas of the iliohypogastric, ilioinguinal, and genitofemoral nerves are located side by side, and variations also exist [17, 21]. According to animal models and clinical studies, the following pathophysiological mechanisms presumably contribute to the occurrence of neuropathic pain: ▬ Continuous abnormal excitation of afferent fibers due to ongoing compressing forces [1] ▬ Impaired intraneural microcirculation that might induce ensuing ischemia and nerve damage [11] ▬ An abnormal excitatory coupling between sympathetic fibers and afferent nociceptive fibers, especially within the spinal ganglion [6] ▬ Hindered or interrupted axonal transport in both directions in the nerve fibers that may result in loss of control of the biochemical activity in the nerve cell body [4] ▬ Central alterations of electrophysiological activities in an afferent neuron that may spread transsynaptically to second-order and higher-order neurons in the spinal cord and brain [2] In conclusion, the effects of nerve injury and nerve damage are not confined to the site of the lesion, as previously expected. Instead, neuropathic pain seems to be a result of an earlier unexpected central nervous plasticity [23], and it is additionally influenced by individually different dispositions. We have no theoretical basis to explain why some patients, but not all, develop neuropathic pain. Thus, different individual dispositions seem to be responsible for the fact that identical nerve lesions cause varying reactions. Experiments in 1980 on different types of rats revealed different measurable amounts of autotomy following identical procedures on nerves. The authors concluded that different genetic dispositions must exist [5]. The experience in hernia surgery presumably will be that only some patients will sustain real neuropathic pain following surgery [21].

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Treatment Modalities for Painful Nerves Microsurgery The above-mentioned microsurgical principles of neurolysis and nerve repair are relevant only if neuroma pain is present. As far as possible, the type of pain has to be estimated preoperatively. Nevertheless, there is a risk of about 30% of inducing an ensuing neuropathic pain. This holds true if nerves of trunk caliber are affected. But considering the particular difficulties with the small abdominal wall nerves encountered in hernia surgery, microsurgery on these nerves is more and more out of discussion. If a neuropathic pain is initially presented, microsurgery even carries the danger of duplicating the pain level in the patient. Thus, regarding neuropathic pain, our experience today is that touching a nerve at the damaged site almost always induces additional central nervous plasticity. This experience holds true independent of the nerve caliber.

Neurotomy We understand neurotomy as nerve transection proximal to the primary nerve lesion. Of course, recurrent neuroma formation will always start and stop about 6–8 weeks later. If the regrown neuroma at the proximal nerve end is imbedded within soft tissue, the risk of ongoing repeated triggering may be reduced. If, for example, we operate on Morton’s neuralgia, neurotomy via a dorsal approach will be the only way to succeed [13]. But patients with Morton’s neuralgia never present with a neuropathic pain syndrome. On the other hand, 27 of 29 laparoscopic »triple neurotomies« of all three inguinal nerves have been quite successful (N. Kleemann, personal communication). Considering the experience with a greater number of hyperpathic pain syndromes in the inguinal area, these results seem to be in contrast to the above-mentioned thesis. The actual impression, therefore, is that neurotomy at least remains under discussion.

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Chapter 23 · Surgical Trauma of Nerves–Causes of Neuropathic Pain, Classification, and Options in Surgical Therapy

Neuromodulation

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The idea of achieving pain relief by electrically stimulating the dorsal columns of the spinal cord (known as spinal cord stimulation or SCS) was derived from the gate control theory by Melzack and Wall in 1965 [7]. According to this concept, stimulation of large afferent A-fibers of peripheral nerves should reduce the pain input to the brain via the small unmyelinated and thinly myelinated C-fibers. Because the conduction velocity of A-fibers is faster than that of the C-fibers, A-fibers were said to have the capacity to »gate out« pain stimuli from transmission to the cortex [7]. Currently, this technique is not only applied on dorsal columns of the spinal cord but also on peripheral nerves [19]. If technically possible, the epineurium of the nerve is pierced, and a quadripolar electrode is pushed slightly into the subepineural space a few centimeters distal or proximal, depending on the affected nerve and its availability [13]. After a test stimulation period of a few days, the external screener is changed to an internal subcutaneously placed pacemaker. In cases of painful involvement of very small nerve branches that are not surgically accessible for the above-mentioned direct nerve stimulation (dPNS), and in cases of excessive scarring, the treatment can consist of subcutaneous peripheral nerve stimulation (sPNS). Here, the electrode is percutaneously advanced to the location of the assumed nerve damage. The intraoperative test stimulation should induce pleasing paresthesias in the distribution of the affected nerve. This method often achieves a good response to painful conditions of injured inguinal nerves and even has an effect on the frequently associated localized tenderness in the area of the scar tissue [22]. But the gold standard in the future may perhaps be a laparoscopic approach. Possover and colleagues reported on their recent experiences applying these techniques to the intrapelvic course of the inguinal nerves by a laparoscopic approach [14, 15]. The great advantages of intraabdominal or pelvic neuromodulation compared with neurotomy are the following:

▬ No additional sensory loss, particularly if intraabdominal »triple neurotomies« (neurotomy of all three inguinal nerves) are used ▬ No risk of inducing a neuropathic pain or duplicating the preexisting pain level

Conclusion The scientific considerations of different types of nerve lesions, secondary fibrosis, microsurgical procedures, and the regeneration process after microsurgery were insufficient for solving the problem of nerve-related pain until today. A differentiation of whether the patient presents with either neuroma pain or neuropathic pain is of great importance. Microsurgical methods, with their risks, can be applied to neuroma pain, and neuromodulation, which carries less risk but is dependent on technical details, can be used for neuropathic pain. In cases of affected inguinal nerves, laparoscopic neuromodulation seems to be a reasonable technical solution in the future, whereas neurotomy is under discussion as a high-risk procedure as far as pain relief is concerned.

References 1. Bennett GJ, Xie Y-K (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87–107 2. Devor M (1988) Central changes mediating neuropathic pain. In: Dubner R, Gebhart GF, Bond MR (Eds) Proceedings of the 5th World Congress on Pain, vol 3. Elsevier, Amsterdam, pp 114–128 3. Edshage S (1964) Peripheral nerve suture. Acta Chir Scand (suppl) 331:1–104 4. Herdegen T, Fiallos-Estrada CE, Bravo R, Zimmermann M (1993) Colocalisation and covariation of c-JUNtranscription factor with galanin in primary afferent neurons with CGRP in spinal motoneurons following transection of rat sciatic nerve. Mol Brain Res 17:147–154 5. Inbal R, Devor M, Tuchendler O, Lieblick (1980) Autotomy following nerve injury: genetic factors in the development of chronic pain. Pain 9:327-337 6. Jänig W (1991) Sympathetic activity during peripheral nerve injury. In: Besson JM, Guilbaud G (eds) Lesions of primary afferent fibers as a tool for the study of clinical pain. Elsevier, Amsterdam, pp 65–82 7. Melzack R, Wall P (1965) Pain mechanisms: a new theory. Science 150:971–979

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8. Millesi H (1992) Chirurgie der peripheren Nerven. Urban & Schwarzenberg, Munich 9. Millesi H, Meissl G, Berger A (1976) Further experiences with interfascicular grafting of the median, ulnar, and radial nerves. J Bone Joint Surg 58A:209–218 10. Millesi H, Meissl G (1981) Consequences of tension at the suture site. In: Gorio A (ed) Posttraumatic peripheral nerve regeneration; experimental basis and clinical implication. Raven Press, New York, pp 277–279 11. Myers RR, Yamamoto T, Yaksh TL, Powell HC (1989) The role of focal ischemia and Wallerian degeneration in peripheral nerve injury producing hyperesthesia. Anesthesiology 78:308–316 12. Noordenbos W, Wall PD (1981) Implications of the failure of nerve resection and graft to cure chronic pain produces by nerve lesion. J Neurol Neurosurg Psychiat 44:1068–1073 13. Penkert G, Fansa H (2004) Peripheral nerve lesions. Springer, Berlin 14. Possover M, Baekelandt J, Chiantera V (2007) The laparoscopic approach to control intractable pelvic neuralgia: from laparoscopic pelvic neurosurgery to the LION technique. Clin J Pain 23(9):821–825 15. Possover M, Baekelandt J, Chiantera V (2007) The laparoscopic implantation of neuroprothesis–LION technique–to control intractable abdomino-pelvic neuralgia. Neuromodul 10:18–23 16. Samii M, Penkert G (1998) Traumatic disorders of the peripheral nervous system. In: Cruz J (ed) Neurological and neurosurgical emergencies. Saunders, Philadelphia, pp 349–362 17. Schumpelik V, Kingsnorth G (1999) Incisional hernia of the abdominal wall. Springer, Berlin 18. Seddon HJ (1943) Three types of nerve injury. Brain 66:237–288 19. Shetter AG, Racz GB, Lewis R, Heavner JE (1997) Peripheral nerve stimulation. In: North RB, Levy RM (eds) Neurosurgical management of pain. Springer, New York, pp 261–270 20. Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74:491–516 21. Töns CH, Schumpelik V (1990) Das Ramus-genitalis-Syndrom nach Hernienoperation. Chir 61:441–443 22. Winkelmüller M (2005) Which nerve is suitable for peripheral nerve stimulation? Presentation at the 15th Workshop, Pain Section, German Society of Neurosurgery 23. Zimmermann M (1994) Basic neurophysiological mechanisms of pain and pain control. In: Horsch S, Claeys L (eds) Spinal cord stimulation. Springer, Berlin, pp 3–18

Discussion Amid: We do a lot of triple-neurectomies in pa-

tients with chronic pain. Our neurosurgeons told us that we should ligate the cut ends in order to

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prevent neuroma formation. I reviewed the literature and I have not found any data concerning this question. What do you think is the better to prevent pain, to ligate the cut ends of the nerve or to implant them in the muscle? What is your personal recommendation? Penkert: There are no conclusive data until now what to do with a nerve when you have cut it. However there are some reports which recommend the implantation of a cut nerve in fatty tissue, others recommend the ligation of a cut nerve. However, we do not have significant data what to do with a nerve end after transsection. In my opinion any additional harm to the nerve is not good. May be after the transsection of a nerve the implantation in a muscle is the best way. But another important thing is that neuropathic pain occurs within a few days after the harm to the nerve, whereas chronic pain occurs within weeks after the damage of a nerve. Schumpelick: The anesthesiologists told us that we should give local anesthesia to the nerve before we cut it, because there is a kind of pain memory. Can you comment on this? And what is the best method to dissect a nerve, better to do it with a scissor or with a scalpel? Penkert: As a neurosurgeon we try to avoid a dissection a nerve. However if necessary you should try minimize the harm to the nerve. May be local anesthesia can be beneficial, but only if there is no additional harm to the nerve. And it doesn’t matter whether you use a scissor or a scalpel. At least it is said, that there is a pain memory. Miserez: You mentioned local neuromodulation. What is about pharmacological neuromodulation? Penkert: Mostly those medicaments have notable side effects. And the most young patients doesn’t accept those side effects. Jacob: Are locally applied steroids justified in case of neuropathic pain? Penkert: The first step should be the field stimulation in the area of the neuropathic pain. If it doesn’t work the second step could be the laparoscopic approach. These are the only things that you can do in case of neuropathic pain following surgery. However it is different in case of chronic pain.

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Risks for Pain–Neuropathic Pain: How Should We Handle the Nerves? D. Kaemmer, R. Rosch, M. Stumpf, J. Otto, K. Junge, U. Klinge V. Schumpelick

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Introduction

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In hernia surgery, interest has been focused more and more on pain, a problem that remained underestimated because only relatively few patients seemed to be affected. Chronic pain evolves in a high percentage after surgery with the need to mobilize or even compress nerves [1]; however, after groin hernia repair, symptoms vary to a high degree [2]. Pain character is mostly neuropathic, but due to overlapping distribution areas it is not clearly related to certain nerves [3]. The neuropathic pain character is accompanied by an inflammatory pain for some time after operation, which is understandable, especially when a mesh was used and foreign material remains in the body. Nerve damage during and chronic pain after hernia repair have been poorly evaluated in the past, but clinical studies illuminate clinical consequences and symptoms [4]. Nevertheless, little experimental data exist to give clear advice on how to handle healthy or damaged nerves in the groin. In groin hernia repair, it is necessary to mobilise the groin nerves traversing the operating field and retract them during the procedure. Furthermore, in recurrent groin hernia repair it is sometimes necessary to resect nerves incorporated in scar tissue. We therefore conducted two pilot studies to evaluate how to handle nerves during groin hernia repair and to advocate for further research. Intraneural fibrosis as a mechanism for nerve dysfunction was of obvious interest, as well as the presence of inflammatory cells revealed by Giemsa staining and markers for inflammation such as COX-2, MMP-2, and CD64 as a marker for activated macrophages.

Materials and Methods In uncastrated male pigs (n=6, control n=1), bilateral Lichtenstein repair was performed using a common technique. Each animal received repair with a small-pore polypropylene mesh (mesh M) on one side and a large-pore polyvinylidene mesh (mesh P) contralaterally. A nerve specimen from an untouched nerve served as control. The follow-up

was 6 months. Iliohypogastric, ilioinguinal, and genitofemoral nerves were explanted bilaterally via a retroperitoneal approach. Nerves were stored in paraformaldehyde 4% and were processed for histology, cross-polarisation microscopy, and immunohistochemistry. Antibodies against MMP-2 (1:1000, Biomol, Hamburg, Germany), CD64 (Helmholtz Institute for Applied Medical Engineering, Aachen, Germany), and COX-2 (DCS Innovative Diagnostic-Systeme, Hamburg, Germany) were applied for immunohistochemical analyses. Collagen I/III ratios were analysed as described previously [5]. Mast cells were detected by Giemsa staining. Histological findings were evaluated using a semiquantitative score ranging from 0 to 4 (0: 0% positive cells; 1: 5% positive cells, 2: 5–30% positive cells; 3: 30–80% positive cells, 4: >80% positive cells), and scores of nerves were pooled. In a second series we evaluated pigs (n=3, control n=1) receiving a neurotomy with cauterisation of the iliohypogastric, ilioinguinal, and genitofemoral nerves on one side and neurotomy without cauterisation contralaterally. The operating procedure included bilateral exploration of the groin region, opening of the inguinal canal, and identification of the nerves. After neurotomy with or without cauterisation, the inguinal canal was closed without using a hernia repair technique. A nerve specimen from an untouched nerve served as control. The follow-up was 8 weeks. Iliohypogastric, ilioinguinal, and genitofemoral nerves were explanted bilaterally via a retroperitoneal approach. Nerves were stored in paraformaldehyde 4% and were processed for histology, cross-polarisation microscopy, and immunohistochemistry as described above.

Results Six months after bilateral Lichtenstein repair, expression of MMP-2, COX-2, and CD64 was increased compared with controls. Collagen I/III ratios were also slightly elevated, implying that a higher relative amount of collagen I was present. No mast cells were detected in either group (Giemsa staining). Altogether, there were no differences between the large-pore and the small-pore meshes (⊡ Fig. 24.1).

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10 9 8

score/ratio

7 6 5 4 3 2 1 0 MMP-2

COX-2 Mesh M

CD 64

Collagen I/III

Mesh P

⊡ Fig. 24.1. Results of first series 6 months after bilateral Lichtenstein repair (Mesh M small-pore polypropylene mesh; Mesh P large-pore polyvinylidene mesh)

10 9 8

score/ratio

7 6 5 4 3 2 1 0

MMP-2

COX-2 cauter

CD 64

Collagen I/III

scissor

Eight weeks after bilateral groin exploration, higher numbers of MMP-2, COX-2, and CD64positive cells were observed compared with control nerves. Expression of MMP-2 was higher than 6 months after Lichtenstein repair. Again, the collagen I/III ratio was increased, and no mast cells were found. This effect at 8 weeks after groin exploration was independent of the method by which neurotomy was performed. The elevations were similar for neurotomy with cauterisation and neurotomy alone (⊡ Fig. 24.2). Neither inflammatory markers nor collagen ratios changed in these two groups, but they were clearly elevated compared with control values.

⊡ Fig. 24.2. Results of second series 8 weeks after bilateral groin exploration

Discussion Patients suffering pain after groin hernia repair have been an underestimated collective in clinical research so far. This is mirrored by the confusion about how to handle intact or damaged nerves during surgery. It is known that cutaneous afferent neurons react more sensibly to damage [6]. Although experimental knowledge exists that little damage is caused by simply mobilising nerves [7], stretching [8] or compressing [9] them leads to detectable and sustaining dysfunction. There has been discussion about the amount of distension that is tolerable [8]; nevertheless, almost always during hernia repair,

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Chapter 24 · Risks for Pain–Neuropathic Pain: How Should We Handle the Nerves?

nerves are at risk for damage because the upper stretching limit is ~15% of nerve length. It has been shown that even without clear detectable nerve damage, pain and measurable dysfunction of the nerves can persist independent of the use of a mesh prosthesis [10]. This supports our finding that no differences exist between different transection methods or between different large-pore meshes. Even after hernia repair, nerves are at risk because compression, such as that caused by hematoma or seroma, can compromise intraneural blood flow. Experimental analyses in the rabbit sciatic nerve revealed a complete interruption of intraneural blood flow at pressures of about 50–70 mmHg [9]. Whether these pressures are evoked by seroma or hematoma formation, for instance, remains to be elucidated, but possible nerve damage should be taken into account when deciding whether and to what extent seromas or hematomas should be treated. It should also be mentioned that a small impairment of nerve integrity and function could possibly be aggravated by continuous or rising pressure.

Conclusion During hernia repair, nerves should be identified and carefully mobilised if necessary to protect nerves traversing the operating field from damage. Stretching of nerves by hooks should be minimised whenever possible. Compression of nerves after hernia repair by hematoma or seroma as a possible source of (further) damage should be avoided. Although 6 months after Lichtenstein repair no clear difference existed between large-pore and small-pore meshes in our model, the impact of alloplastic prostheses on chronic pain remains to be elucidated. This pilot study constitutes a very small sample and lacked a control group using Shouldice repair. Regarding the need for nerve resection during surgery, we observed no difference between neurotomy with and neurotomy without cauterisation in our model. To prevent neuroma formation with the possibility of neuropathic pain, the proximal nerve stump must be provided with the most appropriate

surgical method. If a neuroma is already present, or if resection is necessary for other reasons, the existing literature seems to favour burying the proximal nerve end into muscle, with or without ligation or capping [11, 12]. A general standard procedure is difficult to suggest because of small trial sizes. In the case of inguinal nerves, further research is needed to establish rational treatment.

Acknowledgments We are grateful to Mrs. Ellen Krott for her excellent and careful assistance during this investigation.

References 1. H. Kehlet, T.S. Jensen, C.J. Woolf, Persistent postsurgical pain: risk factors and prevention. Lancet 367 (2006) 1618–1625 2. A.S. Poobalan, J. Bruce, W.C. Smith, et al., A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 19 (2003) 48–54 3. T. Mikkelsen, M.U. Werner, B. Lassen, H. Kehlet, Pain and sensory dysfunction 6 to 12 months after inguinal herniotomy. Anesth Analg 99 (2004) 146–151 4. E.K. Aasvang, B. Brandsborg, B. Christensen, et al., Neurophysiological characterization of postherniotomy pain. Pain 137 (2008) 173–181 5. R. Rosch, K. Junge, M. Knops, et al., Analysis of collageninteracting proteins in patients with incisional hernias. Langenbecks Arch Surg 387 (2003) 427–432 6. P. Hu, E.M. McLachlan, Selective reactions of cutaneous and muscle afferent neurons to peripheral nerve transection in rats. J Neurosci 23 (2003) 10559–10567 7. D.G. Kline, E.R. Hackett, G.D. Davis, M.B. Myers, Effect of mobilization on the blood supply and regeneration of injured nerves. J Surg Res 12 (1972) 254–266 8. J. Haftek, Stretch injury of peripheral nerve. Acute effects of stretching on rabbit nerve. J Bone Joint Surg Br 52 (1970) 354–365 9. K. Ogata, M. Naito, Blood flow of peripheral nerve effects of dissection, stretching and compression. J Hand Surg [Br] 11 (1986) 10–14 10. F. Karakayali, M. Karatas, U. Ozcelik, et al., Influence of synthetic mesh on ilioinguinal nerve motor conduction and chronic groin pain after inguinal herniorrhaphy: a prospective randomized clinical study. Int Surg 92 (2007) 344–350 11. J. Lewin-Kowalik, W. Marcol, K. Kotulska, et al., Prevention and management of painful neuroma. Neurol Med Chir (Tokyo) 46 (2006) 62–67 12. J. Wu, D.T. Chiu, Painful neuromas: a review of treatment modalities. Ann Plast Surg 43 (1999) 661–667

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Discussion Gryska: How do you exactly handle the nerve in

case of implanting it in a muscle? Rosch: We just have done a simple dissection of

the nerves. However there are studies showing that there might be a benefit for the patients if you implant the nerve end in a muscel. And additionally we didn´t see any differences if we have ligated or coagulated the nerve in the retroperitoneal space. However there might be changes in the dorsal route ganglion. Peiper: In Lichtenstein hernia repair the ilioinguinal nerve runs through the operation field and following mesh implantation you achieve a distant contact between the mesh and the nerve. Is there any place in routine to dissect the nerve in this situation? Rosch: If you look to the studies there is no difference between the patient following Lichtenstein repair and Shouldice concerning the postoperative chronic pain. Therefore actually we would recommend any trauma to the nerves in order to avoid damage to the nerve. Amid: In some cases an adequate repair of an inguinal hernia is not possible without dissection of the ilioinguinal nerve. In those cases we dissect the nerve. But now it appears that it is important to implant the nerve in the muscle.

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What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy D. Hegarty

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Chapter 25 · What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy

Introduction

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Inguinal hernias account for 75% of all abdominal wall hernias, with a lifetime risk of 27% in men and 3% in women [1, 2]. The rate of repair of inguinal hernia ranges from 10 per 100,000 of the population in the United Kingdom to 28 per 100,000 in the United States [3]. Of these patients, chronic postoperative inguinal pain occurs in up to 54%. The persistence of postoperative inguinal herniorrhaphy pain for longer than 3 months following surgery has gained interest during the last years, becoming the most important outcome variable besides recurrence rates [4–6] because this pain affects and impairs activities of daily life in 12% of patients [7–10]. Indeed, pain-related sexual dysfunction, including dysejaculation, is now recognised to occur in at least 2% of young men [11]. Therefore, before surgery is considered for a benign disease, complications such as severe chronic pain, with its debilitating effects, must be carefully weighed against the benefits [12]. Many studies have examined the surgical factors that contribute to development of postoperative herniorrhaphy pain. For example, the intraoperative factors shown to be associated with the lower incidence of nondisabling, mild, and moderate chronic pain include the use of lightweight meshes and the laparoscopic approach [13]. The traditional assumption that chronic pain after herniorrhaphy pain is neuropathic in origin, and is secondary to direct surgical trauma or postoperative inflammation of the nerves, has therefore been challenged [14]. As clinicians we need to consider the role of patient-related factors in the development of chronic postherniorrhaphy pain, not just the surgery-related factors. This overview seeks to examine these patient factors and to propose an assessment and management model that integrates new ideas while at the same time maintaining contact with current therapies and approaches but placing them in a more open and appropriate context.

The Biopsychosocial Model The biopsychosocial model proposed by Waddell et al. [15] draws attention to the interaction of the patient’s response to his or her situation and the

impact of the work and social environments, as well as the impact of any tissue abnormality, pain, and relevant biomedical factors on progression through the problem and eventual outcome. For example, psychosocial factors are now acknowledged to predict low back pain outcome far better than do the available physical and biomedical findings [16]. While the bulk of the recent research is still in the area of low back pain, it is reasonable to expect that psychosocial factors also significantly impact other benign musculoskeletal pain states and disabilities such as inguinal herniotomy [17]. In order to propose a clinically relevant assessment and management model that integrates new concepts, compartmentalisation of the important clinical features is required. Fundamental to this compartmentalisation strategy is the gathering of patient-relevant material that can be managed, adapted, accepted, improved, and resolved using a balanced combination of patient and clinical input [18]. Six interrelating compartments need to be assessed, with the potential for management in a parallel fashion. In this way, treatment of a patient with chronic herniotomy pain might include the following: 1. Adequate explanation of the problem, which is dominated by giving reassuring information (e.g. causes, likely course, and normal pain behaviour) 2. An explanation of the treatment and management strategy as well as the likely outcome, using the best available evidence 3. A graded exercise programme to improve muscle weakness and general fitness 4. A combination of rest and activity using principles of pacing and incrementation [19, 20] 5. Encouragement of relaxation, ergonomics, and the appropriate use of transcutaneous electrical nerve stimulation and analgesics for pain management 6. Help with preparations for a graded return to work [21] The precise integration of these compartments is not a recipe to be prescribed; rather, it is guided by the patient’s individual presentation, capacities, and negotiated goals. This article suggests that each

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case of chronic inguinal herniorrhaphy pain can be considered using the following six compartments: 1. Biomedical factors 2. »Flagging« of psychosocial barriers to recovery 3. Reactivation and rehabilitation 4. Identification of physical impairments 5. Encouragement of physical fitness 6. Treatment of pain

Compartment 1: Biomedical Factors When pain arises from particularly private sites or those associated with basic bodily functions, such as urination or ejaculation, the condition becomes complicated by psychological as well as unique physiological issues. These structures have innervation that converges within the central nervous system, making symptoms alone inadequate as diagnostic tools. Even a precise history and meticulous physical examination may result in diagnostic ambiguity. For example, directly asking patients to localise the epicentre of their inguinal pain on anatomical charts does not appear to be helpful [14]. Patients may contribute further to the ambiguity by omitting observations they find to be too embarrassing to describe or discuss (e.g. dysejaculation [11]). Nevertheless, clinicians have a responsibility to ensure that another underlying diagnosis is not being overlooked. Consideration should be given to the possibility of a secondary neurological, gastrointestinal, musculoskeletal, or urological diagnosis to explain the chronic symptoms. ⊡ Table 25.1 highlights some common differential diagnoses that may need to be considered in each individual case [22].

⊡ Table 25.1. Possible differential diagnoses of chronic pain localised to inguinal area structures Gastrointestinal origin  Hernia: recurrent bowel obstruction  Colitis: radiation enterocolitis, Crohn’s disease, ulcerative colitis  Diverticular disease of the colon  Irritable bowel syndrome  Chronic constipation: faecal impaction  Proctalgia fugax  Infectious diarrhoea ▼

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Neurological origin  Postsurgical neuroma: painful scar  Neuralgias (i.e. iliohypogastric, ilioinguinal, genitofemoral)  Postherpetic neuralgia  Peripheral neuropathy  Central pain: post stroke or post spinal cord injury  Neuralgias (i.e. iliohypogastric, ilioinguinal, genitofemoral)  Herniated nucleus pulposus  Guillain-Barré syndrome  Neurofibromatosis Musculoskeletal origin  Thoracic, lumbar, or sacral spinal disease  Pelvic floor or abdominal muscular spasm  Coccygodynia  Fibromyalgia Urological  Interstitial cystitis  Polycystic kidney  Loin pain haematuria  Stag horn calculus  Urethral syndrome  Urethral diverticulum or caruncle  Detrusor dyssynergia Male reproductive  Orchialgia  Prostatodynia, chronic prostatitis, or chronic pelvic pain syndrome  Penile pain Female reproductive (gynaecological) pain Cyclical  Mittelschmerz, other ovarian pain  Primary dysmenorrhoea  Secondary dysmenorrhoea (uterine abnormalities, cervical stenosis, uterine leiomyoma, adenomyosis, imperforate hymen) Noncyclical or atypical cyclical  Adhesions  Endometriosis  Pelvic relaxation, prolapse, retroversion of the uterus  Vulvodynia  Ovarian remnant syndrome  Dyspareunia without vulvodynia  Pelvic congestion syndrome  Adenomyosis  Chronic pelvic pain without obvious pathology Other pain states  Chronic pelvic organ ischaemia  Acute intermittent porphyria  Familial Mediterranean fever  Systemic lupus erythematosus  Psychogenic pain

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Chapter 25 · What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy

Assessment Tool

25

Until recently there was no standardised and validated instrument to assess the severity of postoperative pain following inguinal hernia repair. The Inguinal Pain Questionnaire (IPQ) has evolved over the past number of years. It is a self-administrated questionnaire that assesses the intensity of the pain, its frequency, and the extent to which the pain interferes with daily activity [6, 22]. Evidence now supports the use of the IPQ as an instrument in clinical studies as well as in the clinical routine to assess long-term pain following inguinal hernia surgery [22].

Contribution of Genetic Factors The large interindividual variability in the experience of pain suggests that genetic variability may play an important role in chronic pain. Genetic variants modulating pain continue to be discovered, and researchers expect that genetic information may be exploited to treat pain or to predict those who are at a greater risk of developing pain. At present no clinical research is specifically examining the genetic variants that may contribute to postoperative herniorrhaphy pain. Therefore, we must rely on data from general pain-related genetic research to assess the relationship between genotype and phenotype. For example, functional genetic polymorphisms of catecholamine-O-methyltransferase (COMT) are associated with altered sensitivity to pain induced in an experimental environment [23, 24]. High COMT activity correlates with a risk of developing chronic temporomandibular joint pain [25]. Results of studies in rodents indicate that the susceptibility to develop neuropathic pain has a strong heritable component, but the genes responsible have yet to be identified [26–28]. The GTP cyclohydrolase gene has been proposed to affect pain sensitivity and pain-related outcome following spinal surgery, although this process is not completely clear [29, 30]. Given the complexity of neuropathic pain, it is likely that many genes contribute to the development of chronic pain. Studies are underway to correlate single nucleotide polymorphisms in multiple candidate genes with the risk of developing postinjury neuropathic pain [30].

Compartment 2: »Flagging« of Psychosocial Barriers to Recovery Clinicians should be encouraged to actively screen for, identify, and then appropriately manage relevant psychosocial components to identify patients at risk of developing chronic pain and associated disability problems from an early stage, perhaps even as early as the preoperative assessment [31]. This is not an attempt to label a patient’s chronic postoperative inguinal hernia pain as psychologically mediated, but rather an attempt to identify some of the barriers to recovery that might be present. The »flagging initiative« used in the management of low back pain could be usefully transferred to the area of chronic herniotomy pain. The purpose of developing flags for chronic herniotomy would be to do the following [31, 32]: ▬ Provide a method of screening for psychosocial factors ▬ Provide a systematic approach for assessing psychosocial factors ▬ Suggest strategies for better pain management for those who appear to be at high risk for chronicity The aim of this flagging initiative should be to identify a number of key psychological factors [32]: ▬ Presence of a belief that the pain is harmful or severely disabling ▬ Fear-avoidance behaviour patterns with reduced activity levels ▬ Tendency to low mood and withdrawal from social interaction ▬ Expectation that passive treatments rather than active participation will help In the management of acute and chronic pain states, enquiries about psychosocial factors and their management are highly relevant and need to be addressed. The results of early preventive programmes are persuasive and support the development of prevention programmes in primary care for first-time sufferers; such programmes have been shown to significantly–by eightfold–reduce disability and the risk of becoming chronic, as compared to »treatment as usual« [33]. The pro-

195 Chapter 25 · What To Consider as Clinicians About Chronic Postoperative Pain

gramme includes a thorough examination by a doctor and a physical therapist; information designed to reduce fear, uncertainty, and anxiety; self-care recommendations; and the recommendation to remain active and continue everyday routines [33].

Compartment 3: Reactivation and Rehabilitation Reactivation and rehabilitation are strongly linked to patient beliefs and behaviour, especially those relating to fear and avoidance (see the section on Compartment 2). Patients are often wary of moving or exercising because they lack confidence and have not been given any clear advice or guidance. In situations where they feel safe and supported, patients can find that they are able to start moving normally and without any particularly bad repercussions [34]. A process using the principles of graded exposure is suggested [35, 36]. Negotiating adequate and appropriate functional goals with patients is an important requirement [37]. By commencing with activities and activity goals in an adequate rest–activity ratio, the patient’s confidence will improve, and further activity can be built on from there. For example, being occupied diverts attention away from pain, whereas being inactive leads to deconditioning and is also associated with withdrawal from work and social activities. The consequences of this can result in feelings of hopelessness and helplessness that can lead to the onset of depression. In addition, improved circulation, exchange of metabolites, and healing are promoted by movement. Injured tissues tend to heal to the strength required by the demands put on them [38]. The case for (1) the maintenance of function, activity, or work in the acute management, (2) the early return of function and activity in acute and subacute management, and (3) the reestablishment of normal function in chronic pain-disabled patients is now strong. Patients frequently need help with pain control and pain management (see section on Compartment 6: Treatment of Pain), so this should be ensured as soon as possible.

25

Compartment 4: Identification of Physical Impairments Physiotherapists are experts at observation, examination, and correction of physical abnormalities, such as impairments found in tissue and joint anatomy, biomechanics, tension, range, mobility, strength, movement patterns, and functional activities. Physiotherapists draw on many impairment-focused skills, techniques, and approaches that may coincidentally or intentionally also help relieve pain and improve function [34]. Focused physiotherapy is important and can assist in ensuring the best possible outcome for the patient suffering chronic postoperative inguinal herniorrhaphy pain [34].

Compartment 5: Encouragement of Physical Fitness Physical activity is perhaps the most powerful component in pain management programmes. Increasing fitness is important not only in reversing the disuse syndrome but also in giving a powerful signal to patients that they are beginning to regain control over their musculoskeletal system. It is, therefore, extremely important from both the physical and the psychological points of view [37]. The detrimental effects of inactivity, immobilisation, disuse, deconditioning, and low physical fitness, and the beneficial general health effects related to increased activity and fitness are now well established and extensively reviewed elsewhere. It seems essential for clinicians, whether involved in the management of acute or chronic pain, to quickly involve the patient in the maintenance or improvement of his or her general physical health. Thankfully, a great many of the detrimental effects are, with effort, reversible.

Compartment 6: Treatment of Pain Clearly, a major goal of management is to reactivate patients. Pain management and pain control are important and are often a central feature of good therapy, ensuring the best possible outcome

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Chapter 25 · What To Consider as Clinicians About Chronic Postoperative Pain and Inguinal Herniorrhaphy

for the patient. Targeting the pain source is not always essential, but understanding the antecedents for increases and decreases in the pain can often yield better treatment and management strategies. Readers are referred elsewhere for details on analgesic options, but basic analgesic management in combination with advanced interventional strategies should be considered as appropriate on an individual patient basis. Clearly, a focused and well-directed analgesic programme is critical for each case to provide appropriate pain relief while avoiding overreliance on the interventional/analgesic aspect of the treatment. As with all aspects of pain management, the emphasis is biased towards patient self-management, responsibility, and involvement rather than overdominance by passive and pain-focused treatments [18].

Summary Chronic postoperative inguinal herniorrhaphy pain occurs in up to 54% of patients and significantly impairs activities of daily life, including sexual function [2, 11]. This is particularly disappointing when a complication such as severe pain and its debilitating effects occurs after surgery for a benign disease. Unfortunately, we are unable to predict which individuals are going to develop chronic postoperative pain, a situation that impedes clinicians who need to consider treatment options. This article proposes that we compartmentalise our approach to chronic postoperative inguinal pain so as to perform clinically relevant assessments and use a management model that integrates new ideas, while at the same time maintaining contact with current therapies. By using the concept of six compartments that address the biopsychosocial aspects of the patient’s chronic pain, it is hoped that clinicians will have a model for thoroughly examining each case. In addition, evidence now supports the standardised use of the IPQ as an instrument in clinical studies and in the clinical routine to assess long-term pain following inguinal hernia surgery [22]. We propose that a flagging initiative, similar

to that used for chronic low back pain patients, be considered in inguinal hernia assessment. In the future, it is hoped that candidate pain genes can be identified and exploited to predict those who are at greater risk of developing pain and to benefit chronic postoperative inguinal pain management.

References 1. Kingnorth AN, Bowley DM, Porter C (2003) A prospective study of 1000 hernias: results of the Plymouth Hernia Service. Ann R Coll Surg Engl 85:18–22 2. Jenkins JT, O’Dwyer PJ (2008) Inguinal hernias. Br Med J 336:269–72 3. Delvin HB (1995) Trends in hernia surgery in the land of Astley Cooper. In: Soper NJ (ed) Problems in general surgery, vol 12. Lippincott-Raven, Philadelphia, pp 85–92 4. Bay-Nielsen M, Perkins FM, Kehlet H (2001) Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 233 (1):1–7 5. Poobalan AS, Bruce J, King PM, Chambers WA, Krukowski ZH, Smith WC (2001) Chronic pain and quality of life following open inguinal hernia repair. Br J Surg 88(8):1122– 1126 6. Kehlet H (2008) Chronic pain after groin hernia repair. Br J Surg 95:135-136 7. Aasvang E, Kehlet H (2005) Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 95(1):69–76 8. Callesen T, Bech K, Kehlet H (1999) Prospective study of chronic pain after groin hernia repair. Br J Surg 86(12):1528– 1531 9. Cunningham J, Temple WJ, Mitchell P, Nixon JA, Preshaw RM, Hagen NA (1996) Cooperative hernia study. Pain in the postrepair patient. Ann Surg 224(5):598–602 10. Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA (2003) A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 19(1):48–54 11. Aasvang EK, Mohl B, Kehlet H (2007) Ejaculatory pain: a specific postherniotomy pain syndrome? Anesthesiology 107:298–304 12. Dennis R, O’Riordan D (2007) Risk factors for chronic pain after inguinal hernia repair. Ann R Coll Surg Engl 89:218–220 13. Beldi G, Haupt N, Ipaktchi et al. (2008) Postoperative hyposthesia and pain: qualitative assessment after open and laparoscopic inguinal hernia repair. Surg Endosc 22:129–133 14. Milkkelson T, Werner MU, Lassen B, Kehlet H (2004) Pain and sensory dysfunction 6 to 12 months after inguinal herniotomy. Anesth Analg 99:146–151 15. Waddell G, Main CJ, Morris EW et al. (1984) Chronic low back pain, psychologic distress, and illness behavior. Spine 9:209–213

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16. Watson PJ (1999) Psychosocial assessment. The emergence of a new fashion, or a new tool in physiotherapy for musculoskeletal pain? Physiotherapy 85(10):530–535 17. Borkan JM, Quirk M, Sullivan M (1991) Finding meaning after the fall: injury narratives from elderly hip fracture patients. Soc Sci Med 33:947–957 18. Klaber Moffett J (2002) Back pain: encouraging a selfmanagement approach. Physiother Theory Pract 18:205– 212 19. Harding V (1998) Application of the cognitive-behavioural approach. In: Pitt-Brooke J, Reid H, Lockwood J, et al. (eds) Rehabilitation of movement: theoretical bases of clinical practice. Saunders, London, p 539–583 20. Shorland S (1998) Management of chronic pain following whiplash injuries. In: Gifford LS (ed) Topical issues in pain 1. Whiplash: science and management. Fear-avoidance beliefs and behaviour. CNS Press, Falmouth, pp 115–134 21. Gibson L, Allen S, Strong J (2002) Re-integration into work. In: Strong J, Unruh A, Wright A, et al. (eds) Pain: a textbook for therapists. Churchill Livingstone, Edinburgh, p 267–287 22. Franneby U, Gunnarsson U, Andersson M, et al. (2008) Validation of an inguinal pain questionnaire for assessment of chronic pain after groin hernia repair. Br J Surg 95:488–493 23. Vlaeyen JWS, Linton SJ (2000) Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain 85(3):317–332 24. Zubieta JK, Heitzeg MM, Smith YR, et al. (2003) COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299:1240–1243 25. Diatchenko L, Slade GD, Nackley AG, et al. (2005) Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 14:135–143 25. Mogil JS, Wilson SG, Chesler EJ, et al. (2003) The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad Sci USA 100:4867–4872 27. Mogil JS, Wilson SG, Bon K, et al. (1990) Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 80:67–82 28. Mogil JS, Yu L, Basbaum AI (2000) Pain genes? Natural variation and transgenic mutants. Annu Rev Neurosci 23:777–811 29. Tegeder I, Costigan M, Griffin R, Abele A, et al. (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269–1277 30. Hegarty D, Shorten G (2008) Influence of a selective GTP cyclohydrolase haplotype on clinical outcome, pain intensity and pain perception thresholds following lumbar discectomy. Presented at »Plenary Speaker of the Future« at the British Pain Society 2008 [in press] 31. Watson P, Kendall N (2000) Assessing psychosocial yellow flags. In: Gifford LS (ed) Topical issues in pain 2. Biopsychosocial assessment and management. Relationships and pain. CNS Press, Falmouth, pp 111–129

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32. Main CJ, Watson PJ (2002) The distressed and angry low back pain patient. In: Gifford LS (ed) Topical issues in pain 3. Sympathetic nervous system and pain. Pain management. Clinical effectiveness. CNS Press, Falmouth, pp 177–204 33. Linton SJ (1998) The socioeconomic impact of chronic back pain: is anyone benefiting? Pain 75:163–168 34. Gifford L, Thacker M, Jones M (2006) Physiotherapy and pain. In: McMahon S, Koltzenburg N (eds) Wall and Melzak’s textbook of pain. Churchill Livingstone, Philadelphia, pp 603–617 35. Vlaeyen JWS, Crombez G (1999) Fear of movement/(re) injury, avoidance and pain disability in chronic low back pain patients. Man Ther 4(4):187–195 36. Vlaeyen JWS, Linton SJ (2000) Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain 85(3):317–332 37. Watson P (2000) Psychosocial predictors of outcome from low back pain. In: Gifford LS (ed) Topical issues in pain 2. Biopsychosocial assessment and management. Relationships and pain. CNS Press, Falmouth, pp 85–109 38. Harding V (1999) The role of movement in acute pain. In: Max M (ed) Pain 1999–an updated review. Refresher course syllabus. IASP Press, Seattle, pp 159–169

Discussion Schumpelick: Can you give us a figure of your

success rates? Hegarty: This strategy is not been completely ap-

plied in a uniformed fashioned way in the moment. It has not been studied directly therefore I cannot comment on this. Stumpf: I want to stress on the things you mentioned about the psychological back ground. In our outpatient clinic we started to work with a psychiatrist in order to investigate the influence of psychosomatic reasons for chronic inguinal pain. It seems to be very important to distinguish patients with psychosomatic disorders from other patients with chronic pain. Hegarty: I totally agree with you. Also it is very important to get strategies what is going on in case of female and male patients with chronic pain. Also pain history is very important.

26

Risk Factors for Chronic Pain After Groin Hernia Surgery P. Nordin

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Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

Introduction

26

Assessment of the outcomes of groin hernia surgery has mainly focused on recurrence. However, with modern surgical techniques and the introduction of mesh, the recurrence rate has decreased considerably [1]. More recently there has been increased attention on other outcomes such as chronic pain, convalescence, and patient satisfaction [2–8]. It is now well established from many multicentre/multinational studies that chronic pain after inguinal herniorrhaphy represents the most important and disturbing sequela; it may not only cause discomfort but also limit the individual’s activities of daily living and have a considerable impact on the person’s quality of life [7, 9]. Occurrence rates vary extensively in the literature, which can be explained by the lack of a uniform definition of such pain and of a standardised instrument for its assessment. Also, grading of pain severity and the social consequences has often been limited in studies addressing the risk of long-term pain, and it is often categorised as a dichotomous (yes/no) variable in the literature [10]. The reported prevalence rates of residual pain range between 0% and 53%, but pain impairing daily activities following groin hernia repair is reported at a level around 10% [7, 9]. Because the development of chronic pain after groin hernia repair may have major implications

⊡ Table 26.1. Levels of evidence (RCT randomised controlled trial)

for costs and quality of life, and because no treatment has been shown to be effective, a detailed analysis of potential risk factors and the influence of surgical techniques is important. This chapter contains a review of risk factors for chronic pain following herniorrhaphy. The analysis is based partly on a detailed register-based questionnaire study from the Swedish Hernia Register and partly on the European Guidelines for the Treatment of Inguinal Hernia [11, 12].

Material and Methods European Guidelines for the Treatment of Inguinal Hernia The guidelines are exclusively evidence-based on results from scientific research and are divided into different levels of evidence. The levels vary from the highest level of evidence (1A), which is based on results that have been consistently demonstrated in systematic reviews, to the lowest level (4), which is based only on the opinion of experts (see ⊡ Tables 26.1 and 26.2). This grading of scientific evidence results in different levels of conclusions and grades of recommendations [12]. As part of the European Hernia Society Guidelines for the Treatment of Inguinal Hernia, a review of published findings on risk factors for

⊡ Table 26.2. Grades of recommendation

1A

Systematic review of RCTs with consistent results from individual (homogenous) studies

A

Supported by systematic review and/or at least two randomised controlled trials of good quality

1B

RCTs of good quality

Level of evidence: 1A, 1B

2A

Systematic review of cohort or case-control studies with consistent results from individual (homogenous) studies

B

2B

RCT of poorer quality or cohort or casecontrol studies

C

2C

Outcome studies, descriptive studies

3

Cohort or case-control studies of low quality

4

Expert opinion, generally accepted treatments

Supported by good cohort studies and/or case-control studies Level of evidence: 2A, 2B Supported by case series, cohort studies of low quality, and/or »outcomes« research Level of evidence: 2C, 3

D

Expert opinion, consensus committee Level of evidence: 4

201 Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

chronic pain after groin hernia surgery was carried out. Studies of chronic pain after inguinal hernia repair were identified using the PubMed, Cochrane Library, and Ovid search engines. Any study–randomised, controlled trial, cohort, questionnaire, or follow-up–of adult (>18 years) patients with a primary or recurrent inguinal hernia (asymptomatic or symptomatic; acute or elective) was included. The search was conducted using the term pain combined with inguinal hernia, clinical trial, randomised controlled trial, chronic pain, hernia repair, and neuropathy. Chronic pain is defined by the International Association for the Study of Pain as pain lasting for 3 months or more [13].

Swedish Hernia Register The Swedish Hernia Register (SHR) has compiled detailed information on more than 160,000 groin hernia repairs since its inception in 1992. Every inguinal or femoral hernia operation in patients age 15 or older performed at participating departments is recorded prospectively according to a standardised protocol. Annual checks by external reviewers have found a validity of data of about 98% [4]. For a complete description of the SHR’s recorded data, validity checks, etc., the reader is referred to earlier publications [1, 14]. From the population-based SHR, 3,000 patients age 15–85 years from 59 hospitals were sampled from the 9,280 patients registered as having undergone a primary groin hernia operation in the year 2000. Of these, the 2,853 patients still alive in 2003 were requested to fill out a postal questionnaire to investigate the occurrence of residual pain intensity.

Inguinal Pain Questionnaire The Inguinal Pain Questionnaire (IPQ) is a selfrecording instrument for chronic pain. It has been validated and was shown to have high reliability and validity for assessment of long-term groin pain [15]. Pain intensity is rated on a seven-step fixed-point scale with steps operationally linked

26

with pain behaviour. The questionnaire consists of 18 items, with pain in the contralateral (not operated) groin used as a reference.

Results Results from the SHR-Based Questionnaire Study In the Swedish questionnaire study, 2,456 patients (86%), of whom 2,299 were men and 157 were women, responded after two reminders. In response to a question about the »worst perceived pain last week,« 758 patients (31%) reported pain to some extent. In 144 cases (6%), the pain interfered with daily activities. An age below the median, a high level of pain before the operation, and occurrence of any postoperative complications were found to significantly and independently predict long-term pain in multivariate logistic analysis when »worst pain last week« was used as the outcome variable. The same variables, along with a repair technique using an anterior approach, were found to predict long-term pain with »pain right now« as the outcome variable.

Swedish Hernia Register The SHR so far has no mandatory follow-up, but any reoperation because of chronic pain must be recorded. ⊡ Figure 26.1 presents reoperation rates because of chronic pain within 3 years for the different methods of groin hernia surgery used in Sweden. Plug techniques and open sutured repairs have the highest risk, and totally extraperitoneal (TEP), Lichtenstein, and Shouldice repairs have the lowest risk of reoperation for chronic pain.

Results from the European Guidelines The guidelines search covered all relevant literature until April 2007 and literature of all level-1A and/or level-1B studies until May 2008. The results were divided into different levels of evidence.

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Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

0.61%

0.5%

0.46% 0.4%

0.41%

0.3% 0.25% 0.2% 0.19% 0.17%

26

0.1%

0.10%

0.0%

Lichtenstein

Shouldice

Open nonmesh

Open mesh

Open preperitoneal

Plug

TAPP

TEP

⊡ Fig. 26.1. Reoperation rates within 3 years because of chronic pain; n=142 (TAPP transabdominal preperitoneal repair; TEP totally extraperitoneal repair)

⊡ Table 26.3. Results of multivariate logistic analysis of risk factors predicting any level of pain versus no pain regarding the perception of »pain right now« (OR odds ratio; CI confidence interval) Factor

Patients perceiving pain, n (%)

Univariate model OR 95% CI

Multivariate model OR 95% CI

Age Median ≤59 years Median >59 years

345/1,026 (34%) 205/976 (21%)

1 Reference 0.55 0.45–0.68

1 Reference 0.54 0.44–0.66

Gender Male Female

517/1,878 (28%) 33/124 (27%)

1 Reference 1.11 0.71–1.73

Preoperative pain level Low High

176/966 (18%) 374/1,036 (36%)

1 Reference 2.49 2.02–3.08

1 Reference 2.43 1.97–2.99

Postoperative complications No Yes

498/1,865 (27%) 52/137 (38%)

1 Reference 1.76 1.21–2.57

1 Reference 1.77 1.22–2.57

Hernia repair Anterior approach Posterior approach

532/1,907 (28%) 18/95 (19%)

1 Reference 0.58 0.34–0.99

1 Reference 0.56 0.33–0.95

Hernia anatomy Femoral Medial Lateral

5/34 (15%) 171/602 (28%) 340/1,228 (28%)

1 Reference 2.90 1.02–8.25 2.44 0.87–6.83

203 Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

26

Gender

Nonmesh Repair

Level 2B: Females were found to have a higher risk of developing postoperative chronic pain than males did [9].

Level 1B: Most studies comparing mesh with nonmesh repair report less chronic pain with mesh repair [7, 9, 20].

Age

Standard Polypropylene Mesh

Level 2A: In a randomised controlled trial (RCT) with 319 patients comparing three open mesh techniques, chronic pain was found to be related to younger age, and two population-based questionnaire studies found that younger age significantly increased the risk [11, 16, 17].

Level 1B: In three RCTs comparing lightweight mesh with standard polypropylene mesh, two indicated that the use of lightweight mesh was associated with significantly less pain on exercise after 6 months [24] and less pain of any severity at 12 months in the lightweight group [25]. In the third study [26], there was no difference in neuralgic pain, hypoaesthesia, or hyperaesthesia between the groups.

Preoperative Pain Level 2A: Preoperative pain seems to increase the risk of developing chronic pain, according to some studies [7, 11, 17].

Mesh Fixation

Level 2B: Preoperative chronic pain conditions such as headache, back pain, and irritable bowel syndrome were found to correlate significantly with the development of chronic pain [5].

Fibrin glue and nonfixation techniques have been compared with mesh fixation with staples and tackers in laparoscopic hernia operations. Reduced early postoperative pain with the nonstapling techniques was found, but there were no differences in the risk for late chronic pain [27–29].

Strong Postoperative Pain

No Identification of Inguinal Nerves

Level 2B: In an RCT with 319 patients comparing three open mesh techniques, chronic pain was found to be related to stronger pain directly after the operation [16]. In an RCT with 867 patients and 5-year follow-up comparing transabdominal preperitoneal (TAPP) and Shouldice repair, no differences in late discomfort were found. However, severe pain during the first postoperative week was a risk factor for late discomfort in the Shouldice group [18].

Level 1A: Based on three randomised studies, chronic pain after identification and division of the ilioinguinal nerve was similar to that after identification and preservation of the nerve [30]. Level 2B: Two cohort studies suggested that the incidence of chronic pain was significantly lower after identification of all inguinal nerves compared with no identification of any nerves [30].

Preoperative Chronic Pain Conditions

Method of Repair Level 1A: The incidence of chronic pain is reported to be lower after TAPP and TEP repair compared to open anterior surgery, with or without mesh [9, 17, 19–22]. Other manifestations of nerve lesions, numbness, and paraesthesia, are also fewer following laparoscopic surgery [19, 22]. Meta-analysis of 41 trials of laparoscopic versus open groin hernia repair with 7,161 participants (individual patient data were available for 4,165) revealed less persisting pain and numbness after laparoscopic repair [23].

Intraoperative Nerve Damage Intraoperative nerve damage in relation to the development of chronic pain has been discussed. There is a lack of well-defined studies on intraoperative lesions of nerves in the inguinal region in relation to development of chronic pain [9].

Reoperation for Recurrence Level 1B: Patients undergoing reoperative surgery for recurrent hernia were at risk of developing chronic neuralgia, with a fourfold higher rate of moderate or severe chronic pain [7, 9, 17].

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Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

Discussion

26

The risk of chronic postherniorrhaphy pain may be the most important outcome or quality variable to consider in groin hernia surgery. Variables that are most associated with an increased risk of residual postherniorrhaphy pain include nonmesh repair, techniques involving an anterior approach, younger age, preoperative pain and preoperative chronic pain conditions, strong postoperative pain, lack of intraoperative identification of inguinal nerves, and reoperation for recurrence. Postoperative complications were found to be linked to an increased risk of long-term pain in the SHR-based questionnaire study. This is in accordance with two other trials [17–31]. In most studies, however, chronic pain seems not to have been evaluated at all among the reported complications. These findings, correlating chronic pain with complications, indicate that postoperative complications may serve as an important variable for improvement of surgical quality regarding risks for long-term postherniorrhaphy pain. Among the risk factors, only the operative technique and complications can be controlled by the surgeon. Inguinal hernia repair, a relatively small operation, is followed by a substantial risk of chronic pain. At least three nerves may be damaged during the procedure. However, quantification of the level of pain, the exact cause, grading of the severity, and social consequences of the pain have not been well described. Occurrence rates vary extensively in the literature, which can be explained by the lack of a uniform definition of such pain and of a standardised instrument for its assessment [10]. Assessing chronic pain was not the primary aim of most of the available studies. In a systematic review of the literature for the years 1987–2000, the frequency of chronic pain after hernia repair, which was reported in 40 studies, ranged from 0% to 53% [7]. Pain impairing daily activities following groin hernia repair was reported by about 10% of patients when asked about it 1–2 years postoperatively [3]. These reports are predominantly from public hospitals and university institutions and are in contrast to results from dedicated hernia cen-

tres, where the incidence of reported chronic pain is 0–2% [32–34]. The incidence rates for chronic postherniorrhaphy pain derived from large register-based questionnaire studies have also varied [3, 11, 17, 35]. This may also be explained by the lack of standardised principles for assessing pain. The questionnaires used have not been uniform in the definition of pain, the length of time since surgery, and the intensity of pain. Among the strengths of register studies is the fact that many surgeons with varying backgrounds and (hernia) surgery experience are involved. The prevalence of residual pain after hernia surgery estimated in these studies is considered to mirror population-based results, and an unselected and unbiased population is involved. Furthermore, scientific studies with sufficient power to reveal risk factors for chronic postherniorrhaphy pain would require considerably large samples. In the Swedish register-based questionnaire study, references to the disabling effect of residual pain with different daily activities were explored by using the IPQ, which links pain with daily function. In the IPQ, pain intensity is rated on a sevenstep fixed-point rating scale, with steps operationally linked with pain behaviour. The questionnaire has been validated and was shown to have high reliability and validity for assessing long-term groin pain [15]. Most of the published studies on laparoscopic versus open inguinal hernia repair show a tendency towards less chronic pain after laparoscopic techniques. However, cautious interpretation is recommended. Many of the studies concerning laparoscopic treatment of inguinal hernia are of poor quality regarding pain assessment, as pain was not the primary outcome variable. But the data from the better-designed trials may suggest that the development of chronic pain is less or similar after laparoscopic hernia repair. The results from recent randomised clinical trials comparing laparoscopic TEP or TAPP repair with open tension-free mesh repair are conflicting: Some trials resulted in a lower prevalence of postoperative pain in the laparoscopic group [36–38], whereas other trials showed no difference between the treatment arms [31, 39].

205 Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

Future studies should focus on identifying preoperative risk factors; providing a detailed description of the surgical technique (e.g. nerve identification), the type and intensity of pain, and the social consequences of the pain; and incorporating a detailed postoperative follow-up with characterisation of the pain. Most of the existing treatments for chronic postherniorrhaphy pain have been unsuccessful so far and need to be further evaluated. However, prevention is better than treatment, and rational prevention and management techniques can be developed for the future only by careful studies and assessment of the causes of pain.

References 1. Nilsson E, Haapaniemi S (1998) Hernia registers and specialization. Surg Clin North Am 78:1141–1155 2. Callesen T, Bech K, Kehlet H (1999) Prospective study of chronic pain after groin hernia repair. Br J Surg 86:1528– 1531 3. Bay-Nielsen M, Perkins FM, Kehlet H (2001) Danish hernia database. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 223:1–7 4. Blyth FM, March LM, Brnabic AJ, Jorm LR, Williamson M, Cousins MJ (2001) Chronic pain in Australia: a prevalence study. Pain 89:127–134 5. Courtney CA, Duffy K, Serpell MG, O’Dwyer PJ (2002) Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 89:1310–1314 6. Schwab JR, Beaird DA, Ramshaw BJ, Franklin JS, Duncan TD, Wilson RA (2002) After 10 years and 1903 inguinal hernias, what is the outcome for the laparoscopic repair? Surg Endosc 16:1201–1206 7. Poobalan AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA (2003) A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 19(1):48–54 8. Winslow ER, Quasebarth M, Brunt LM (2004) Perioperative outcomes and complications of open vs extraperitoneal inguinal hernia repair in a mature surgical practice. Surg Endosc 18:221–227 9. Aasvang E, Kehlet H (2005) Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 95(1):69–76 10. Kehlet H, Bay-Nielsen M, Kingsnorth A (2002) Chronic postherniorrhaphy pain: a call for uniform assessment. Hernia 6:178–181 11. Fränneby U, Sandblom G, Nordin P, Nyre’n O, Gunnarsson U (2006) Risk factors for long term pain after hernia surgery. Ann Surg 244:212–219 12. Simons MP, Aufenacker T, Bay-Nielsen M, et al. (2009) European Hernia Society guidelines on the treatment of inguinal hernia in adult patients. Hernia 13:343–403

26

13. Classification of chronic pain (1986). Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy. Pain Suppl 3:S1– S226 14. SBR (Swedish Hernia Register Web site). Available at www. svensktbrackregister.se. Accessed 8 May 2005 15. Fränneby U, Gunnarsson U, Andersson M, Heuman R, Nordin P, Nyre’n O (2008) Validation of the inguinal pain questionnaire; a novel instrument for evaluation of chronic pain after hernia surgery. Br J Surg 95(4):488– 493 16. Nienhuijs SW, Boelsen OB, Strobbe LJ (2005) Pain after anterior mesh repair. J Am Coll Surg 200(6):885–889 17. Kalliomäki ML, Meyerson J, Gunnarsson U, Gordh T, Sandblom G (2008) Long-term pain after inguinal hernia repair in a population-based cohort; risk factors and interference with daily activities. Eur J Pain 12:214–225 18. Berndsen FH, Petersson U, Arvidsson D, Leijonmarck CE, Rudberg C, Smedberg S, Montgomery A; SMIL Study Group (2007) Discomfort five years after endoscopic and Shouldice inguinal hernia repair: a randomised trial with 867 patients. A report from the SMIL study group. Hernia 11:307–313 19. Bittner R, Sauerland S, Schmedt CG (2005) Comparison of endoscopic techniques vs Shouldice and other open nonmesh techniques for inguinal hernia repair: a metaanalysis of randomized controlled trials. Surg Endosc 19(5):605–615 20. The EU Hernia Trialists Collaboration (2002) Repair of groin hernia with synthetic mesh: meta-analysis of randomized controlled trials. Ann Surg 235(3):322–332 21. Koninger J, Redecke J, Butters M (2004) Chronic pain after hernia repair: a randomized trial comparing Shouldice, Lichtenstein and TAPP. Langenbecks Arch Surg 389(5):361–365 22. Schmedt CG, Sauerland S, Bittner R (2005) Comparison of endoscopic procedures vs Lichtenstein and other open mesh techniques for inguinal hernia repair: a meta-analysis of randomized controlled trials. Surg Endosc 19(2):188–199 23. Grant AM; The EU Hernia Trialsits Collaboration (2002) Laparoscopic versus open groin hernia repair: meta-analysis of randomised trials based on individual patient data. Hernia 6(1):2–10 24. Post S, Weiss B, Willer M, Neufang T, Lorenz D (2004) Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair. Br J Surg 91(1):44–48 25. O´Dwyer PJ, Kingsnorth AN, Molloy RG, Small PK, Lammers B, Horeyseck G (2005) Randomized clinical trial assessing impact of a lightweight or heavyweight mesh on chronic pain after inguinal hernia repair. Br J Surg 92(2):166–170 26. Bringman S, Wollert S, Osterberg J, Smedberg S, Granlund H, Heikkinen TJ (2006) Three-year results of a randomized clinical trial of lightweight or standard polypropylene

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31.

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Chapter 26 · Risk Factors for Chronic Pain After Groin Hernia Surgery

mesh in Lichtenstein repair of primary inguinal hernia. Br J Surg 93(9):1056–1059 Lovisetto F, Zonta S, Rora E, Mazzilli M, Bardone M, Bottero L, Faillace G, Longoni M (2007) Use of human fibrin glue (Tissucol) versus staples for mesh fixation in laparoscopic transabdominal preperitoneal hernioplasty: a prospective, randomized study. Ann Surg 245(2):222– 231 Smith AI, Royston CM, Sedman PC (1999) Stapled and nonstapled laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair. A prospective randomized study. Surg Endosc 13(8):804–806 Lau H (2005) Fibrin sealant versus mechanical stapling for mesh fixation during endoscopic extraperitoneal inguinal hernioplasty: a randomized prospective trial. Ann Surg 242:670–675 Wijsmuller AR, van Veen RN, Bosch JL, Lange JF, Kleinrensink GJ, Jeekel J, Lange JF (2007) Nerve management during open hernia repair. Br J Surg 94:17–22 Hawn MT, Itani KM, Giobbie-Hurder A, McCarthy M Jr, Jonasson O, Neumayer LA (2006) Patient-reported outcomes after inguinal herniorrhaphy. Surgery 140(2):198– 205 Kark AE, Kurzer MN, Belsham PA (1998) Three thousand one hundred seventy-five primary inguinal hernia repairs: advantages of ambulatory open mesh repair using local anesthesia. J Am Coll Surg 186:447–455 Amid PK, Lichtenstein IL (1998) Long-term results and presentation of data of the Lichtenstein open tensionfree hernioplasty. Hernia 2:89–94 Rutkow IM, Robbins AW (1998) The mesh plug technique for recurrent groin herniorrhaphy: a nine-year experience of 407 repairs. Surgery 124:844–847 Bay-Nielsen M, Nilsson E, Nordin P, Kehlet H (2004) Chronic pain after open mesh and sutured repair of indirect inguinal hernia in young males. Br J Surg 91:1372–1376 Douek M, Smith G, Oshowo A, Stoker DL, Wellwood JM (2003) Prospective randomised controlled trial of laparoscopic versus open inguinal hernia mesh repair: five year follow up. BMJ 2003;326:1012–1013 McCormack K, Scott NW, Go PM, Ross S, Grant AM; EU Hernia Trialists Collaboration (2003) Laparoscopic techniques versus open techniques for inguinal hernia repair. Cochrane Database Syst Rev 1:CD001785 Grant AM, Scott NW, O’Dwyer PJ (2004) Five-year follow-up of a randomized trial to assess pain and numbness after laparoscopic or open repair of groin hernia. Br J Surg 91:1570–1574 Wright D, Paterson C, Scott N, Hair A, O’Dwyer PJ (2002) Five-year follow-up of patients undergoing laparoscopic or open groin hernia repair: a randomized controlled trial. Ann Surg 235:333–337

Discussion Smeds: What is strong pain in these types of recommendations? How should we understand strong pain? Nordin: There is no scale in the guidelines. Miserez: The intraoperative nerve injury is a predictor for developing postoperative chronic pain? However I think that we do not have any prospective studies concerning this special question. Can you comment on this? Nordin: It is very difficult to give a comment on this, because it is not mentioned in every trial. But the balance if this is the main reason or not is very difficult to see in the trials. Köckerling: There are two reasons why TEP gives the best results regarding the development of chronic postoperative pain. One is that you never touch the nerves during that procedure. The second and very important point is that you normally do not fix the mesh. Nordin: You are right. However we have to wait for new studies comparing open a laparoscopic hernia repair. Kehlet: We cannot interpret the literature as you have done it. We should select every study were pain as outcome has been asked as a yes or no question, because it has no meaning. And additionally we should have a close look to those patients who have severe chronic pain with social consequences. Nordin: We will consider this in the next guidelines. Schumpelick: How many people of the Swedish hernia trial answered to your questionnaire? How many percent of the patients answered to your questionnaire? How representative are your data? Nordin: In a frequency of over 80% answered to the questionnaire. Penkert: I would like to give a short remark. Very often I heard about pain preoperatively as predicting factor to get chronic pain after the operation. We as neurosurgeons know that some patients feel inguinal pain which is caused by an alteration of a nerve in the L4-L5 intervertebral joint. Therefore ask your patients for such pains before you will perform an inguinal hernia repair.

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Ischemic Inflammatory Response Syndrome as an Alternative Explanation for Postherniorrhaphy Pain M. Stanton-Hicks

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Chapter 27 · Ischemic Inflammatory Response Syndrome as an Alternative Explanation for Postherniorrhaphy Pain

Introduction

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In general, moderate to severe postherniorrhaphy pain occurs in 10% of patients. The incidence is higher after recurrent repair (22%) than after initial surgery (3%) [1]. Other factors increasing the risk of postherniorrhaphy pain are poor postoperative pain control, female gender, young age, and surgical nerve damage. Although abnormal inflammatory response is also proposed as a cause of chronic postherniorrhaphy pain, the specific signs and symptoms that would satisfy a diagnosis of complex regional pain syndrome (CRPS; also known as reflex sympathetic dystrophy or Sudeck’s atrophy) are lacking. In fact, a strong argument can be made that most postherniorrhaphy pain is neuropathic in nature and is a direct expression of neurogenic inflammation in the territory of an injured nerve or nerves. This article discusses the supporting literature and ideas that have been raised at this symposium. In addition, it presents the new criteria used to define CRPS, along with recent validation studies.

Literature Review Preoperative risk factors for the development of postherniorrhaphy pain include severe preexisting chronic pain at any site in the body and a surgical approach that poses a greater risk for nerve damage. In their review, Aasvang and Kehlet identified a number of hernia repair studies that specified pain as an adverse outcome [2]. While most studies of hernia surgery focus on measures to reduce the rate of recurrence, it is only during the past 10 years that chronic postsurgical pain has received increasing attention. These have taken the form of randomized controlled trials and nonrandomized studies. The role of chronic pain unassociated with hernia pain in the development of postherniorrhaphy pain is well established. Conditions such as chronic back pain, irritable bowel syndrome, headache, and peptic ulcer correlate significantly with the development of chronic pain [3, 4]. The role of surgical technique as it relates to open versus laparoscopic repair is described elsewhere in this text. With respect to neurologic ex-

amination of patients with postherniorrhaphy pain, only a small number of studies, including Aasvang and Kehlet’s review, have reported that a physical examination was done, and only one of these included a detailed neurological examination and careful sensory testing at 6 and 12 months [5–9].

Chronic Regional Pain Syndrome The definition of CRPS includes the following: 1. The presence of an initiating noxious event or cause of immobilization 2. Continued pain, allodynia, or hyperalgesia, with the pain being disproportionate to any inciting event 3. Evidence at some point of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain 4. The diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction. In CRPS type I, previously known as reflex sympathetic dystrophy or RSD, there is no evidence of major nerve damage [10]. CRPS type II describes the condition in which evidence of major nerve damage exists [11]. With the introduction of a definition that is truly descriptive and does not imply any mechanistic overtones, the sensitivity for diagnosis was increased, but at the expense of specificity. At the time that the taxonomy underwent its change, it was recognized that these criteria would be revised and refined by longitudinal and epidemiological studies. An initial attempt was undertaken to provide internal validation through a multicenter study using factor analysis as a statistical technique [12]. Analysis of the data in 123 patients revealed that patients clustered in four specifically perceived groups. The first subgroup had unique signs and symptoms indicating a disorder of pain processing. The second subgroup included skin color and temperature changes, indicating vasomotor dysfunction. In the third subgroup, signs and symptoms showed evidence of edema and sudomotor dysfunction. The fourth subgroup had trophic signs and symptoms.

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⊡ Table 27.1. Modified clinical diagnostic criteria

⊡ Table 27.2. Modified research diagnostic criteria

1. Continuing pain disproportionate to any inciting event 2. Must report at least one symptom in three of the four categories: – Sensory: hyperesthesia and/or allodynia – Vasomotor: temperature asymmetry and/or skin color changes and/or skin color asymmetry – Sudomotor/edema: edema and/or sweating and/ or sweating asymmetry – Motor/trophic: decreased range of motion and/ or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 3. Must display at least one sign in two or more of the following categories: – Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch) and/or deep somatic pressure and/or joint movement – Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or skin color asymmetry – Sudomotor/edema: evidence of edema and/or sweating and/or sweating asymmetry – Motor/trophic: evidence of a decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 4. There is no other diagnosis to better explain the signs and symptoms.

1. Continuing pain disproportionate to any inciting event 2. Must report at least one symptom in each of the four following categories: – Sensory: hyperesthesia and/or allodynia – Vasomotor: temperature asymmetry and/or skin color changes and/or skin color asymmetry – Sudomotor/edema: edema and/or sweating and/ or sweating asymmetry – Motor/trophic: a decreased range of motion and/ or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 3. Must display at least one sign at the time of evaluation in two or more of the following categories: – Sensory: evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch) and/or deep somatic pressure and/or joint movement – Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or skin color asymmetry – Sudomotor/edema: evidence of edema and/or sweating and/or sweating asymmetry – Motor/trophic: evidence of a decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 4. There is no other diagnosis to better explain the signs and symptoms.

⊡ Table 27.3. Summary of sensitivity and specificity for the proposed clinical and research criteria [13] Criterion type

Symptoms required for diagnosis

Signs required for diagnosis

Sensitivity

Specificity

Clinical

3

2

0.85

0.69

Research

4

2

0.70

0.96

External validation of the International Association for the Study of Pain (IASP) criteria compared the criteria to findings in CRPS patients, with the application of similar criteria for other types of neuropathic pain. For example, a CRPS patient group defined by the IASP criteria can be compared to patients with non-CRPS neuropathic pain such as that seen in diabetic neuropathy or posthepatic neuralgia. To test the proposed criteria further, the ability to discriminate between CRPS and non-CRPS neuropathic pain requires the iden-

tification of certain rules, which include meeting two of four sign categories and three of four symptom categories. The course of this syndrome shows extreme variability over time. Two versions of the proposed diagnostic criteria–clinical and research– have been specified (⊡ Tables 27.1–27.3) [13]. In summary, the IASP diagnostic criteria provide an objective means to make decisions concerning the identification of those conditions that represent CRPS in which there is significant autonomic dysfunction or other painful condi-

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Chapter 27 · Ischemic Inflammatory Response Syndrome as an Alternative Explanation for Postherniorrhaphy Pain

tions, such as a type of neuropathic pain. The current CRPS criteria and now improved validity are designed to reduce the incidence of medical overutilization. The data also underscore the fact that a failure to acknowledge motor/trophic signs and symptoms in the current criteria may prevent CRPS from being distinguished from other neuropathic syndromes.

Comparison of Inflammatory and Neuropathic Pain After Herniorrhaphy

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If one considers the three types of pain–nociceptive, inflammatory, and neuropathic–the former is clearly associated with the acute stimulation of mechanical, chemical, and thermal nociceptors. The former aspect is normally a perioperative phenomenon, and a lack of adequate control is a strong risk factor for the development of chronic postsurgical pain. Chronic inflammatory pain, on the other hand, results from ongoing tissue injury in response to a chronic stimulus, such as sensitization of nociceptors to mechanical or chemical activity. This peripheral pain may be associated with synaptic plasticity in the spinal cord, with the development of central sensitization. Normally this is self-limiting, and the associated pathophysiological response will generally run a course of days or weeks, but it could become chronic if the source of spinal input remains. Neuropathic pain occurs after injury to nerves or their transmission systems within the spinal cord and brain. The hallmark of neuropathic pain is loss of sensation in association with hypersensitivity. The partial or complete loss of sensory input is a source of positive neurological activity that is expressed by spontaneous pain and hypersensitivity, including allodynia, hyperalgesia, and disordered sensation (dysesthesia). Furthermore, light touch or gentle pressure in deeper tissues of the affected region might give rise to hyperalgesia. Neuropathic pain, in contrast to inflammatory or nociceptic pain, is associated with atopic neurologic activity in the central nervous system

that occurs spontaneously, i.e., without external evoked stimuli, a so-called ectopic pacemaker. Biochemical changes in the synaptic transmission, changes in gene transcription, and upregulation of the A2-δ subunits of voltage-gated calcium channels all play a part in injury-induced central sensitization. Tumor necrosis factor δ (TNFδ), a pain-signaling substance, sensitizes axons, and microglia in the spinal cord are activated, both of which increase the overall response at dorsal horn neurons, sensitization, and central transmission. Typically, loss of Aδ-fibers and C-fibers from peripheral nerves is associated with Aß-fiber sprouting with errant synapses to those second-order neurons vacated by the loss of the Aδ-fibers and C-fibers. The role of heritable characteristics clearly influences the expression of neuropathic pain. Animal studies have demonstrated these traits [14]. The results of future studies may allow identification of those genes responsible for the development of injury-induced neuropathic pain. With the foregoing in mind, nerve injury occurring during herniorrhaphy may in itself not cause ongoing chronic neuropathic pain. Pain preceding herniorrhaphy and other predisposing genetic factors may also be important prerequisites for the development of long-standing postherniorrhaphy pain in susceptible individuals. Given our contemporary uncertainty at predicting many of these factors, and given the technical variables of surgery (open versus laparoscopic), it would be advisable to avoid nerve injury and to certainly not deliberately resect any of the nerves in the inguinal region. Continuing improvements in morbidity with newer laparoscopic techniques should further reduce the incidence of postherniorrhaphy pain. If chronic postsurgical pain is associated with signs and symptoms that fulfill the criteria for CRPS, then its differential diagnosis should be distinct from that of neuropathic pain that is secondary to traumatic nerve injury. Obviously, prevention of neuropathic pain–which, when chronic, is a neurodegenerative disease, with maladaptive consequences in the nervous system–should be prevented at all costs. Although CRPS after hernia surgery is possible, its prevalence in the surgical hernia population is rare.

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References

Smeds: What is the incidence of CRPS I? Stanton-Hicks: I have never seen a case of CRPS I

1. Poobalan AS, Bruce J, Smith WC, et al. A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 2003; 19:48–54 2. Aasvang E, Kehlet H. Chronic postoperative pain: the case of inguinal herniorrhaphy. Br J Anaesth 2005; 95:69–76 3. Courtney CA, Duffy K, Serpell MG, et al. Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 2002; 89:1310–4 4. Wright D, Paterson C, Scott N, et al. Five year follow-up of patients undergoing laparoscopic or open groin hernia repair: a randomized controlled trial. Ann Surg 2002; 235:333–7 5. Heikkinen T, Bringman S, Ohtonen P, et al. Five year outcome of laparoscopic and Lichtenstein hernioplasties. Surg Endosc 2004; 18:518–22 6. Liem MS, van Duyn EB, van der GY, et al. Recurrences after conventional anterior and laparoscopic inguinal hernia repair; a randomized comparison. Ann Surg 203; 237:136–41 7. Mikkelsen T, Werner MU, Lassen B, et al. Pain and sensory dysfunction 6 to 12 months after inguinal herniotomy. Anesth Analg 2004; 99:146–51 8. Picchio M, Palimento D, Attanasio U, et al. Randomized controlled trial of preservation or elective division of ilioinguinal nerve on open inguinal hernia repair with polypropylene mesh I. Arch Surg 2004;139:755–8 9. Verstraete L, Swannet H. Long-term follow-up after Lichtenstein hernioplasty in a general surgical unit. Hernia 2003; 7:185–90 10. Stanton-Hicks M, Jänig W, Hassenbusch S, et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain 1995; 63:127–133 11. Merskey H, Bogduk H (eds) Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. IASP Press, Seattle, 1994 12. Harden RN, Bruehl S, Galer BS, et al. Complex regional pain syndrome: are the IASP diagnostic criteria valid and sufficiently comprehensive? Pain 1999; 83:211–219 13. Harden RN, Bruehl S, Stanton-Hicks M, Wilson PR. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med 2007; 8(4):326–31 14. Devor M, Raber P. Heritability of symptoms in an experimental model of neuropathic pain. Pain 1990; 42:51–67

of the inguinal region. But if you have damage to the nerve it is CRPS II by definition. But we have published a case of CRPS I following breast augmentation. Therefore the inguinal region is just the same problem in another area.

Discussion Amid: What is your definition of neuroma pre-

cisely? And what is the value of mesh material in developing a neuroma? Stanton-Hicks: I find it hard to believe that the mesh acts by pressure. But I also believe that the fibers of the mesh can cut fibers of the nerves.

28

Postoperative CRPS in Inguinal Hernia Patients U. Klinge, A. Fiebeler, M. K. Tur

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Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

Introduction

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Chronic pain is a frequent result after surgical hernia repair and probably the most difficult complication to treat. Whereas we have several excellent options for handling a recurrence, therapy of chronic pain may be frustrating, at least in some patients, and causes a lot of trouble for the surgeon as well as for the patient. Almost the majority of patients report some kind of mild complaints following hernia repair, but some patients suffer considerably. Feeling that they cannot live with this pain, they look for any treatment to get rid of it, and they often undergo one surgical revision after another. Usually, one of the first options is a revision operation, assuming that some of the local nerves are entrapped in sutures, clips, or scar tissue. In these patients, a neurectomy is usually performed. Although in some cases it may not be possible to identify and resect all three nerves (ilioinguinal nerve, iliohypogastric nerve, and genital branch of the genitofemoral nerve), or the morphological analysis of the nerves may reveal no significant pathology, most patients show complete or partial relief of their complaints. However, in some patients the complaints remain, sometimes even getting worse, starting a series of many fruitless attempts to alleviate the discomfort. If these patients had been treated with adequate neurectomy of all three nerves, what else might be the reason for such failures, and how can we identify those patients beforehand to avoid frustrating operations?

Patients with Neuropathic Pain: Subgroup with Complex Regional Pain Syndrome Not Responding to Surgical Therapy There is no doubt that pain is related to nerves and that there are many ways to cause or intensify pain. But apart from technical reasons, which depend on the surgical procedure and the surgeon, patientrelated aspects must be considered, too. Several clinical studies have demonstrated that pain is mainly a problem of younger patients and that the risk increases with the number of previous op-

erations and the extent of local scar tissue. Each of these factors or a combination of them may favour the development of pain and, correspondingly, will influence the success of a revision operation. Whereas pain caused by entrapment through a clip may be cured causally by neurectomy [1], pain due to pathology of the wound healing process (involving age, smoking, local nerve regeneration, etc.) is more complex and difficult to address. Generally, pain is classified as either nociceptive, which represents a physiological signal from injured tissue (= wound pain), or neuropathic, in which a malfunction of a nerve leads to pain signalling to the brain. Whereas the first is assumed to disappear after healing of the wound, it is mainly the latter that is accused of causing chronic pain. Recently, Aasvang et al. [2] demonstrated that large- and small-fibre dysfunction can be detected in all patients following hernia repair but is more profound in pain patients. Correspondingly, some sort of nerve dysfunction seems to be common after surgery in the groin. However, classification as neuropathic pain seems to be too nonspecific for selecting therapeutic options. In a 1999 review in Lancet, Woolf and Mannion [3] stated the following: ▬ Pharmacotherapy for neuropathic pain has been disappointing. ▬ There is no treatment to prevent the development of neuropathic pain. ▬ There is no treatment to adequately, predictably, and specifically control established neuropathic pain. ▬ There are no predictors to indicate, which patient will develop neuropathic pain. ▬ As a tool to define treatment strategy, symptoms alone are not useful because they are not equivalent to mechanisms. Although consideration of neuropathic pain is too inaccurate, this view neglects to account for two different mechanisms that may contribute to nerval function: either direct damage or pathological triggering by perinerval stimuli. In accordance, Aasvang et al. [2], who investigated postoperative complaints after mesh repair of groin hernia, concluded that »whether the underlying pathophysiological mechanisms are related to direct intraoperative nerve in-

215 Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

jury or nerve injury due to an inflammatory (mesh) response remains to be determined.« In this context, it may be helpful to adopt the experiences of other medical fields. Stanton-Hicks published a review on the concept of complex regional pain syndrome (CRPS) [4]. CRPS is characterised by the presence of continuing pain, allodynia, or hyperalgesia after nerve injury that is not necessarily limited to the distribution of a specific nerve and is often accompanied by oedema, changes of skin blood flow, or abnormal sudomotor activity. Two types of CRPS have been recognised. Type I corresponds to reflex sympathetic dystrophy and occurs without a definable nerve lesion. Type II, formerly called causalgia, refers to cases in which a definable nerve lesion is present, but this is still controversially discussed [5]. Despite the extreme variability of the patients’ symptoms–which are quite similar to Sudeck’s atrophy–there seems to be a subgroup of patients who suffer in an outstandingly severe manner from their pain. Often, the pain is not restricted to a circumscribed area that can be related to a nerve; instead, it is characterised by intense, burning sensations and is poorly localised, appearing rather as neuropathic inflammatory pain, with an inflammatory reaction triggered by neural malfunction. It may be hypothesised that these patients may not be treatable by operations because any surgical revision might boost the local disturbance of tissue integrity [6]. In cases of nerve injury, the axonal regeneration after Wallerian degeneration fails to reinnervate the proper end organs in these patients. In an analysis of mesh samples that had been explanted because of chronic pain, some samples revealed misguided growth of the nerves directed towards the filament, indicating an inhibition of Schwann cells by foreign body reaction (⊡ Fig. 28.1). In others, the neuropathic inflammation was accompanied by fibrotic degeneration of nerves with focal axonal degeneration and regeneration of axon sprouts into the surrounding tissue (⊡ Fig. 28.2). The following patient history may be a typical example of a patient with chronic pain that can be resolved by operation. The pain started with the implantation of a mesh, with no clip fixation, in the right groin for a recurrent hernia. Immediately, the

28

patient suffered from paraesthesia, possibly caused by damage of the anterior cutaneous branch of the femoral nerve, although another neurologist suspected damage to the genitofemoral nerve. After explantation of a heavyweight polypropylene mesh that had shrunken from 15×10 cm to 13×4.5 cm, the patient showed a complete recovery. In contrast, a patient with expected CRPS, who received a suture repair of a primary hernia represents a totally different history. In this example, within the first 2 weeks the patient underwent two revisions, the first for pain and the second for hae-

⊡ Fig. 28.1. Explanted polypropylene mesh from patient with chronic pain, with growth of nerve fibre directed towards the polypropylene filament

⊡ Fig. 28.2. Explanted polypropylene mesh from patient with chronic pain, with axon sprouts regenerating into the surrounding tissue

216

28

Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

matoma. Three months later, a third revision was done with neurectomy. After transcutaneous electric stimulation for more than 1 year, retroperitoneal neurectomy of the iliohypogastric and ilioinguinal nerves followed, which resulted in temporary improvement for only 2 weeks. One year later, laparoscopic extraperitoneal revision and reneurectomy of the genitofemoral nerve did not lead to any improvement. A fourth revision 1 year later for recurrence was combined with lateral neurectomy and gave relief only for some weeks. The patient’s final status is characterised by severe pain in the entire lower abdomen, both at rest and under strain, and a demanding consumption of opioids as painkillers, and has been leading to inability to work any longer. Because several patients have experienced the same series of frustrating operations finally leading to invalidity, a specific »response« of these patients to the tissue injury of a groin hernia repair may be suspected. In this regard, the concept of CRPS may offer a valuable tool for selecting patients at high risk for poor outcomes after surgical revision–if it is possible to identify patients in this subgroup preoperatively. These patients may get a better benefit from nonsurgical therapies, such as local therapy with anti-inflammatory drugs or therapeutic injections of glucocorticoids [7]. About 30–40% of patients are considered to suffer from pain that may be classified as neuropathic [8, 9], but is not clear whether it is a part of CRPS. Which patients will probably get some benefit from an operation, and which will not?

so entrapment of a nerve had been assumed but not proven. The patients were contacted by phone, and the success of therapy was coded as follows: 1. Complete relief (CR) 2. Still experiencing intermittent attacks (IA) 3. No improvement despite revision (NI) 4. Conservative therapy (CT). All of the patients had undergone at least one surgical revision, and only three had submitted to a conservative therapy. The remaining 40 were treated with either neurectomy or explantation of a heavyweight small-pore polypropylene mesh. Results provided by telephone revealed complete relief in 13 patients, intermittent attacks in 13, and no improvement in 14. Comparing the various therapeutic outcomes, patient age did not show any significant difference among the four groups. Interestingly, the mean age of all patients was considerably lower (46.8±12.7 years) than the mean age of patients with groin hernia disease. Although males were slightly more likely to be rid of their pain, this did not reach statistical significance. As an attempt to identify patients with CRPS, we assumed that these patients do not have pain that occurs immediately after operation and then remains constant but instead have pain that develops after a considerable delay and then increases constantly (⊡ Fig. 28.3). Patients with CRPS are not

Preoperative Assessment of CRPS To find an answer, we analysed 186 patients who had been seen in our clinic for chronic pain in the abdominal wall in the years 2002–2007. In 52 patients (34%), the pain was related to previous hernia repair in the groin. Therapeutic success could be verified in 43 of them. Many of these patients had had multiple previous operations, and the causal relevance of the specific impact is hard to identify. However, they reported rather complex individual histories. The youngest patient was 16 years old. The pain occurred immediately after hernia repair and was resolved by surgical revision,

Pain

Time ⊡ Fig. 28.3. Time course of pain after hernia repair. Direct damage to the nerve, such as by entrapment in a clip or suture, is assumed to occur directly postoperatively, remaining constant afterwards. This is seen in most patients. In contrast, some patients are pain-free for some time after the operation, but then after a delay of months or even years they newly develop pain, which constantly increases

28

217 Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

expected to respond to a diagnostic pain block with local anaesthesia within 1 h, and they are not expected to show any significant relief. In patients without CRPS, it should be possible to relate the pain to the supply area of certain nerves, whereas in patients with CRPS it is not. To analyse patients, we created a CRPS scoring system consisting of the following three aspects: 1. For pain: 1= immediate postoperative pain; 2= delay/increasing pain 2. For block with local anaesthetics: 1= relief; 2= no relief 3. For anatomical relationship: 1= related to nerve area; 2= diffuse/not related to nerve area. To apply this CRPS score, we assigned 2 points to those signs assumed to indicate CRPS and only 1 point for the others (⊡ Table 28.1). Correspondingly, a sum of 6 points indicates the presence of CRPS, whereas 3 points reflects a low probability for CRPS. Therefore, the success of a surgical

⊡ Table 28.1. Complex regional pain syndrome (CRPS) scores of 43 patients with chronic pain. Pain: 1= immediate pain postoperatively; 2= delay/increasing pain. Block with local anaesthetics: 1= relief; 2= no relief. Anatomical relationship: 1= related to nerve area; 2= diffuse/not related to nerve area. Success of therapy: CR complete relief; IA intermittent attacks; NI not improved; CT conservative therapy Sum of CRPS score points

3

4

5

6

n

23

8

9

3

%

53%

19%

21%

7%

Therapeutic outcome

CRPS suspected

CR

11

3

IA

7

4

2

NI (= CRPS ?)

5

1

7

CT (= CRPS ?)

1 3

No CRPS

CRPS

5

4

3

2

1 r=0.6, p< 0.01

0 2

3

4

5

6

7

CRPS score ⊡ Fig. 28.4. Patients (n=43) treated in the surgical department of the RWTH Aachen 2002–2007 for chronic pain after groin hernia repair. Therapy success is coded as 1= complete relief, 2= intermittent attacks, 3= not improved, 4= conservative therapy. For method of scoring for complex regional pain

syndrome (CRPS), see Table 28.1. Sums vary between 3 and 6 points; 3 points are assumed to not represent CRPS, whereas 6 points are suspected to represent CRPS. The diameter of the points is related to the number of patients with a similar constellation

218

Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

therapy should be highest for patients without CRPS and lowest for patients with CRPS. Indeed, the analysis of correlation shows a statistically significant relationship between our CRPS scores and the success of therapy, confirming that patients scoring 5 and 6 should be treated conservatively (⊡ Fig. 28.4). The correlation coefficient r between the therapy index and the CRPS score was 0.6. However, six of 21 patients, whose treatment success was rated as NI or CT scored less than 5 points on the CRPS score, indicating that this scoring system needs to be improved, particularly with regard to sensitivity. Fortunately, only two of the patients with successful therapies (CR, IA) had more than 4 points in their CRPS scores, confirming the specificity of the score for excluding patients from surgical revision.

28

References 1.

2.

3.

4. 5. 6.

7.

Conclusion The concept of CRPS has proven to be helpful for understanding why some patients may fail to respond to surgical therapy. In many patients, chronic pain is caused by several different local reasons that can be influenced technically, either by neurectomy or mesh explantation. The presence of CRPS represents a systemic biological problem of tissue response that will not respond to any local repair, a concept that is already widely accepted for the treatment of causalgia or Sudeck’s atrophy, both diseases with considerable similarities. The assumption that 25% of the patients with chronic pain possibly have CRPS is well in accordance with the failure rate of 20–30% after surgical therapy. In the future, the validity of the proposed CRPS scoring system should be confirmed by comparing it with other methods and measurements. Despite the extremely complex pathogenesis of chronic pain, it appears to be possible to identify patients with CRPS preoperatively. Future studies will show whether our arbitrary CRPS score can be improved by integrating further factors, such as a history of painkillers, detectable alteration of skin temperature, modified skin reaction to heat and cold stimulus, signs of atrophy, or a pathological sweat secretion test.

8.

9.

JP Miller, F Acar, VB Kaimaktchiev, SH Gultekin, KJ Burchiel: Pathology of ilioinguinal neuropathy produced by mesh entrapment: case report and literature review. Hernia 2008, 12:213–6 EK Aasvang, B Brandsborg, B Christensen, TS Jensen, H Kehlet: Neurophysiological characterization of postherniotomy pain. Pain 2008, 137:173–81 CJ Woolf, RJ Mannion: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999, 353:1959–64 M Stanton-Hicks: Complex regional pain syndrome. Anesthesiol Clin North Am 2003, 21:733–44 GD Schott: Complex? Regional? Pain? Syndrome? Pract Neurol 2007, 7:145–57 H Li, W Xie, JA Strong, JM Zhang: Systemic antiinflammatory corticosteroid reduces mechanical pain behavior, sympathetic sprouting, and elevation of proinflammatory cytokines in a rat model of neuropathic pain. Anesthesiology 2007, 107:469-77 S Aroori, RA Spence: Chronic pain after hernia surgery–an informed consent issue. Ulster Med J 2007, 76:136–40 S Massaron, S Bona, U Fumagalli, F Battafarano, U Elmore, R Rosati: Analysis of post-surgical pain after inguinal hernia repair: a prospective study of 1,440 operations. Hernia 2007, 11:517–25 MJ Loos, RM Roumen, MR Scheltinga: Classifying postherniorrhaphy pain syndromes following elective inguinal hernia repair. World J Surg 2007, 31:1760–1765; discussion 1766–1767

Discussion Kehlet: In my opinion you are on the wrong track.

But that is the reason why we are here to discuss this problem. How can you say that we should not operate on patients with chronic noziceptor pain? I find no evidence for that. To say that there are CRPS I and II is too simple, there are more subtypes. I ask for mulitcentre collaboration with detailed neurophysiological, psychological and genetically characterization of the patients to find out which type of chronic pain we have. We have to look at the spinal and cortical mechanisms of pain productions and separate them out to different groups. And then we should study the different types of intervention. Klinge: First of all is a question of definition. It is not precisely clear what is noziceptive pain and what is precisely CRPS. There are still a lot of

219 Chapter 28 · Postoperative CRPS in Inguinal Hernia Patients

controversial issues in this matter. Second point is that there are so many factors that are responsible. And if you include all these factors which are responsible for such a pain you have a different treatment for every patient. And probably this will not be helpful for our young surgeons in the outpatient clinics. This is such a proposal to identify subgroups. Thought this cannot reflect the specific individual situation. But the main question is whether to make a neurectomy or not. Muschaweck: You recommended a local treatment with local anesthesia. What do you think about a mixture of local anesthesia and cortisone? Klinge: First of all there is clear evidence that there is beneficial effect of combination with steroids in therapeutically injection. The other point is the diagnosis. There is difference in those patients who do not respond to the injection and feel pain even while the injection comparing to those patients who respond for instance at least for one hour to the injection of local anesthesia. Stanton-Hicks: What diagnostic criteria did you use to diagnose the CRPS? What clinical signs and symptoms? Klinge: In this preliminary study we only looked to the patients with chronic pain and grouped them to two groups. I am sure that this is not a good definition of CRPS. It is probably a sub grouping of patients with chronic pain. Probably CRPS is not the right term but it is helpful. Smeds: I want add a practical thing. As we know in 80% of the patients with chronic pain the pain will improve within the first year after the operation. Therefore we should at least wait one year before performing another operation. Klinge: There are may be different ways how to treat a decision tree to make an immediate operation or not. I am convinced that the most patients we will not see within the first 6 month after operation. Köckerling: Before we name this problem a Sudeck of the groin we absolutely should be sure that there are no morphological reasons for the chronic pain. Schumpelick: What to do now? Is there some practical advice for a practical surgeon? What to do with a patient with pain in the groin? Klinge: I want to simplify it.

28

Kehlet: There is one thing that we can conclude:

We don´t understand this problem completely. We need multicentre trials to collect enough patients, because the problem is too complicated. Amid: Two third of the patients did not have mesh repair. How can you correlate mesh repair with the pain if it is not a technical error? Klinge: Just briefly. In our laboraty we have collected about 600 mesh explants. In nearly 94% of the patients in whom the explantation was done due to chronic pain it was a heavy-weight mesh small porous polypropylene mesh.

29

Chronic Pain After Open Mesh Repair of Incisional Hernia M. Kurzer, A. Kark, S. T. Hussain

222

Chapter 29 · Chronic Pain After Open Mesh Repair of Incisional Hernia

Introduction

29

Chronic or long-term pain following open incisional hernia repair is poorly documented. Traditionally, studies of incisional hernia repair have focussed only on short-term complications (infection, haematoma), major morbidity, hospital stay, and recurrence. Chronic pain (defined as pain persisting more than 3 months postoperatively [1]) has not been perceived as a significant issue, a similar situation to that for inguinal hernia repair until recently. Indeed, a recent review of surgical treatment of incisional hernia [2] did not mention postoperative pain at all. However, with surgeons’ increasing awareness of the importance of patientreported outcomes [3], long-term pain following incisional hernia repair is increasingly recognised as a significant clinical problem. Although it can occur following open or laparoscopic repair, this article will confine itself to the problem of chronic postoperative pain after open mesh repair.

How Common Is Chronic Pain After Open Incisional Hernia Repair? McLanahan and colleagues were among the first to document chronic pain following incisional hernia repair and discuss its clinical significance [4]. At 12 months following a sublay mesh repair, 45% of

patients still had some symptoms of discomfort, although most were infrequent and mild. However, 11% of patients described the pain as moderate to severe, and 7% said it limited their activities. In addition, 34% thought they could feel the mesh. In this article, McLanahan et al. also stressed the importance of patient satisfaction and of asking patients for their assessment of the operation. Burger et al. [5] and Pajaanen and Hermunen [6] found the incidence of long-term pain to be 13% and 20%, respectively, after sublay mesh repair. Kingsnorth, using an onlay technique, reported similar figures [7]. Two of these studies [6, 7] found that in 9% or 10% of patients, respectively, this pain limited their daily activities. The list includes both onlay and sublay techniques, with an incidence of chronic pain ranging from 13% to 60%. Some of this wide variation may relate to how the pain was assessed. In a study of three different techniques reported by Korenkov et al., an extremely high proportion, 61%, of patients in the onlay mesh group reported postoperative pain [8]. Infection complications led to this multicentre study being halted, and it may be that variations in technique and other technical factors were responsible for this high incidence of pain and complications. Other groups have also recognised that pain following open incisional hernia repair is a real issue that should be addressed [9, 10]. These studies are listed in ⊡ Table 29.1.

⊡ Table 29.1. Studies addressing pain following open incisional hernia repair (nr not recorded) First author

Year

Mesh position

n

Follow-up, months

Discomfort/ some pain, %

Severe pain, %

Limitation in activities, %

Sugerman [10]

1996

Prefascial

98

20

6

nr

nr

MacLanahan [4]

1997

Sublay

106

>12

55

11

7

Müller [23]

1998

Sublay

41

17

7–30

nr

30

Martin-Duce [11]

2001

Sublay

284

72

28

nr

nr

Korenkov [8]

2002

Onlay

54

12

61

nr

nr

Paajanen [6]

2004

Sublay

84

36

20

4

10

Burger [5]

2004

Sublay

84

81

20

nr

nr

Machairas [9]

2004

Onlay

43

54

7

nr

nr

Kurzer [18]

2008

Sublay

106

95

3

0

0

Kingsnorth [7]

2008

Onlay

116

15

18

nr

9

223 Chapter 29 · Chronic Pain After Open Mesh Repair of Incisional Hernia

Aetiology of the Pain Martin-Duce et al. reported a 28% incidence of chronic postoperative pain in 152 incisional hernia patients [11]. The pain was felt laterally along the spigelian line and was thought to be related to the method of mesh attachment, with nonabsorbable sutures. Its incidence decreased when the surgeons modified their technique of mesh attachment and used absorbable sutures. Paajanen and Hermunen, too, believed that nonabsorbable peripheral sutures were the cause of postoperative pain, due to either tension in the sutures or nerve entrapment [6]. Costalat et al. [12] and Cubertafond et al. [13] held similar views. The aetiology of this pain may be similar to that seen following mesh attachment at its periphery with transfascial sutures in laparoscopic repair. The long-term follow-up of a Dutch randomised trial found the incidence of scarring or superficial pain to be similar whether a sutured or mesh repair was used [5]. However, abdominal pain was less frequent in the mesh repair patients, and the researchers concluded that much of the discomfort was due to midline tension associated with fascial closure, which is more likely in sutured-only patients.

Mesh as the Cause of Pain? Perhaps because our recent recognition of chronic pain as an important sequela of incisional hernia repair has coincided with the widespread use of mesh, the mesh itself has been thought to be a causative factor. The Aachen group, who have extensive experience with the sublay mesh repair technique, have found that a significant proportion of patients complain of paraesthesia and discomfort at the periphery of the mesh, as well as a syndrome of abdominal stiffness after open mesh incisional hernia repair. In a number of patients these symptoms are troublesome enough to require further surgery and mesh removal. Histological examination of the explanted mesh has revealed extensive scar tissue, forming what is termed a scar plate. This sensation of abdominal restriction, or corsage, had earlier

29

been recognised by French surgeons following insertion of large pieces of mesh or sublay repair of massive incisional hernias [12, 13].

Mechanism of Mesh-Associated Pain There is now ample evidence that nonabsorbable alloplastic meshes made of polypropylene or polyester excite an inflammatory foreign body reaction that progresses to chronic inflammation and fibrosis [14, 15]. This reaction is related to the size and type of the mesh fibres and is also host dependent. Most research has focused on polypropylene mesh, in which the total amount of polypropylene and the pore size are probably the chief determinants of the extent and duration of the inflammatory response [16, 17]. With small-pore (sometimes called heavyweight) meshes, the areas of scar tissue that form around individual fibres meet and coalesce, a phenomenon known as bridging. The consequent formation of a thick, rigid scar plate is responsible for the discomfort and stiffness felt by the patient. Histological examination of explanted mesh in this situation has also demonstrated nerve entrapment within the scar tissue, another factor in the aetiology of the pain. With pore sizes greater than 4 mm, there is a less acute inflammatory reaction, fibrosis is limited to the perifilamentary area, and the pores between the fibres are filled with fat rather than fibrotic scar tissue.

Other Complaints with Various Meshes A study comparing three different meshes found that 59% of patients implanted with one type of standard-weight mesh complained of paraesthesia in the region of the periphery of the mesh, compared with only 4% of patients implanted with a lightweight mesh (⊡ Table 29.2) [17]. The technique of three-dimensional stereography of the abdominal wall in postrepair patients showed an increase in stiffness, and this occurred whichever mesh was used. However, the extent of stiffness increased with mesh weight and was inversely

224

29

Chapter 29 · Chronic Pain After Open Mesh Repair of Incisional Hernia

⊡ Table 29.2. Symptoms following sublay incisional hernia repair with different meshes (from Welty et al. [17])

⊡ Table 29.3. Postoperative questionnaire to incisional hernia patients

Symptoms %

Marlex

Atrium

Vypro

Paraesthesiae

59

16

4

Complaints, heavy work

17

16

7

Complaints, daily activities

17

0

4

Complaints at rest

9

3

0

1. Can you remember if you had much pain or discomfort from the hernia before it was repaired or was there just a swelling? 2. If you had pain or discomfort before the operation, is this now better or improved? 3. Do you have abdominal or scar pain now? 4. Did you think about just leaving it? 5. Are you pleased/satisfied with the operation? 6. Is the repair still sound or do you think the hernia might have come back?

proportional to mesh pore size. Moreover, the stiffness in the lightweight (or large pore size) group diminished over time. This study also found that restricted mobility of the abdominal wall and an increase in the rate of patient complaints correlated with the morphological development of a strong scar plate [17]. The clinical evidence is, however, slightly equivocal, as a recent randomised multicentre study of 165 patients failed to show a significant difference (clinically or statistically) between standard-weight and lightweight mesh in terms of interference with daily activities.

Results from the British Hernia Centre In January 2008 we wrote to 106 patients who had undergone open mesh incisional hernia repair at our institution over the previous 10 years [18]. The technique used was an open sublay repair with standard-weight polypropylene mesh, and the overall recurrence rate was 4%. At the time of writing, 68 patients had replied to the questionnaire (⊡ Table 29.3). Before the operation, 70% of patients had some degree of pain or discomfort, and in the vast majority this was improved after operation (⊡ Table 29.4). Three patients who had not had preoperative pain had symptoms of discomfort postoperatively, although this did not interfere with their daily activities, and they were pleased to be rid of their hernia. In this retrospective study, chronic postoperative pain was not seen as a clinical problem.

⊡ Table 29.4. Questionnaire replies, 68/106 n=68

Yes

No

1

Preoperative pain?

47 (70%)

21 (30%)

2

Pain better now?

45 (95%)

2 improved

3

Any pain now?

5

63

4

How disabling?

0

68

5

No operation option?

6

Satisfied?

68

0a

7

Recurrence

0

68

aNeutral

or no response on questionnaire

Summary and Conclusion Clinically important pain following open mesh repair of incisional hernia has an incidence of approximately 10–20%. It can occur after both onlay and sublay techniques, although the nature of the pain may differ. The aetiology of the pain is probably multifactorial and includes tension in the repair, nerve entrapment in sutures, and meshassociated inflammation and scar plate formation. Whether it is related to preoperative symptoms (as in inguinal hernia) is a question that has not yet been addressed. At present we also lack data regarding what patients think about these symptoms and how much these symptoms affect daily activities. Is

225 Chapter 29 · Chronic Pain After Open Mesh Repair of Incisional Hernia

mild postoperative discomfort a price that patients are willing to pay to be rid of an uncomfortable, unsightly, enlarging, and potentially lifethreatening abdominal swelling? This information will be acquired only through accurate preoperative assessment, more assiduous follow-up, and recognition of the importance of patient-reported outcomes [19–21]. Indeed, the whole subject of incisional hernia repair is hampered by a »lack of prospective high-quality studies« [21, 22]. Future progress and improved results will come not only from technical factors (including improvements in mesh technology) but also from better understanding of the indications for surgery and the development of guidelines for appropriate patient selection.

References 1. International Association for the Study of Pain (1999). Classification of chronic pain. Description of chronic pain syndromes and definitions of pain terms. Pain Suppl 3:S1– 226 2. Cassar K, Munro A (2002). Surgical treatment of incisional hernia. Br J Surg 89:534-545. 3. Holt PJ, Poloniecki JD, Thompson MM (2008). How to improve surgical outcomes. Br Med J 336:900–901 4. McLanahan D, King L, Weems C, et al. (1997). Retrorectus prosthetic mesh repair of midline abdominal hernia. Am J Surg 173:445-449 5. Burger JW, Liujendijk RW, Hop WC, et al. (2004). Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–583; discussion 83–85 6. Paajanen H, Hermunen H (2004). Long-term pain and recurrence after repair of ventral incisional hernias by open mesh: clinical and MRI study. Langenbecks Arch Surg 389:366–370 7. Kingsnorth A (2008). Open onlay mesh repair for major abdominal wall hernias with selective use of components separation and fibrin sealant. World J Surg 32:26–30 8. Korenkov M, Sauerland S, Arndt M, et al. (2002). Randomized clinical trial of suture repair, polypropylene mesh or autodermal hernioplasty for incisional hernia. Br J Surg 89:50–56 9. Machairas A, Misiakos EP, Liakakos T, et al. (2004). Incisional hernioplasty with extraperitoneal onlay polyester mesh. Am Surg 70:726–729 10. Sugerman HJ, Kellum JMJ, Reinesm HD, et al. (1996). Greater risk of incisional hernia with morbidly obese than steroid-dependent patients and low recurrence with prefascial polypropylene mesh. Am J Surg 171:80–84

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11. Martin-Duce A, Noguerales R, Villeta R, et al. (2001). Modifications to Rives technique for midline incisional hernia repair. Hernia 5:70–72 12. Costalat G, Noel P, Vernhet G (1991). Technique de cure d’eventration par prothese parietale. Ann Chir 45:882–888 13. Cubertafond P, Sava P, Gainant A, et al. (1989). Cure chirurgical des eventrations post-operatoires par plaque prothetique. Chirurgie 115:66–71 14. Klinge U, Klosterhalfen B, Muller M, et al. (1999). Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 165:665–673 15. Klosterhalfen B, Klinge U, Hermanns B, et al. (2000). Pathology of traditional surgical nets for hernia repair after long-term implantation in humans. Chirurg 71:43–51 16. Klosterhalfen B, Junge K, Hermanns B, et al. (2002). Influence of implantation interval on the long-term biocompatibility of surgical mesh. Br J Surg 89:1043–1048 17. Welty G, Klinge U, Klosterhalfen B, et al. (2001). Functional impairment and complaints following incisional hernia repair with different polypropylene meshes. Hernia 5:142–147 18. Kurzer M, Kark A, Selouk S, et al. (2008). Open mesh repair of incisional hernia using a sublay technique: long-term follow-up. World J Surg 32:31–36 19. Bitzer EM, Lorenz C, Nickel S, et al. (2008). Patient-reported outcomes in hernia repair. Hernia 12:407–414 20. Nieuwenhuizen J, Kleinrensink GJ, Hop WC, et al. (2008). Indications for incisional hernia repair: an international questionnaire among hernia surgeons. Hernia 12:223–225 21. Nieuwenhuizen JA, Halm J, Jeekel J, et al. (2007). Natural course of incisional hernia and indications for repair. Scand J Surg 96:293–296 22. Muller-Riemenschneider F, Roll S, Friedrich M, et al. (2007). Long-term effectiveness of interventions promoting physical activity: a systematic review. Surg Endosc 21:2127–2136 23. Müller M, Klinge U, Conze J, Schumpelick V. (1998). Abdominal wall compliance after Marlex mesh implantation for incisional hernia repair. Hernia 2:113–117

Discussion Conze: Every large hernia was once a small hernia.

Therefore I think that there is a development of size, but you didn’t mention it in your talk. Kurzer: In my opinion the size of the hernia stays stable at one point with a scary border. Conze: Another thing is that we have to differentiate emergency cases. About 2–3% of emergency operations were done because of incarcerated hernias. Therefore it is important to differentiate who is of risk for developing an incarceration.

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Clinical Results After Open Mesh Repair V. Schumpelick, M. Binnebösel, J. Conze

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Chapter 30 · Clinical Results After Open Mesh Repair

The incidence of incisional hernia formation remains unchanged between 10% and 20%, depending on the length of follow-up [1]. It is still one of the most common complications after abdominal surgery. Today a large variety of surgical options for incisional hernia repair are available [2–4]. On the basis of data from 2006, approximately 40,000 incisional hernia repairs were performed in Germany. Although the results of conventional suture repair are known to have a recurrence rate of up to 60% depending on the time of follow-up, almost every second incisional hernia is still repaired with a suture repair. The other half are performed with the help of nonresorbable mesh prostheses. Unfortunately, the operative coding system does not facilitate differentiation of the surgical procedures. There is great variability in the placement of the mesh within the abdominal wall: intraabdominal as an intraperitoneal onlay mesh, epifascial onto the anterior fascia (onlay), or behind the muscles onto the posterior rectus sheath (retromuscular/sublay). Another important technical aspect is the intended role of the mesh–whether it is used for augmentation (reinforcement) or as a replacement (bridging of the defect) of the abdominal wall (⊡ Fig. 30.1). This shows the problem and limitations of a review of open mesh techniques: We still have no sufficient data available!

First of all, we are confronted with a mix of terms: incisional or ventral hernia? These are often used as synonyms, as well as epigastric and umbilical hernia. This does not make sense because the anatomy and pathophysiology of primary and umbilical hernias differ from that for incisional hernias. Second, within the group of incisional hernias, no differentiation is made between the different hernia locations: median, paramedian, lateral, transverse, subxiphoid oblique, or flank incisions. This is due to lack of a classification system for abdominal wall hernias. There have been several attempts in the past to develop a classification to make comparison of different surgical procedures possible. In 1998 there was a first expert meeting under the guidance of the GREPA/European Hernia Society (EHS) to create a classification for incisional hernias. Besides the location of the previous incision, the experts took defect size and reducibility into account, but no proposal resulted from this meeting [5]. Several other attempts followed, but to date, none has found its way into the clinical routine. Too many parameters need to be considered: location, defect size, width or length of the defect area, symptomatology, reducibility, number of recurrences or visibility. One parameter that all classification attempts include is the size of

onlay sublay ipom

AUGMENTATION onlay sublay

DEFECT-BRIDGING ⊡ Fig. 30.1. Role of mesh

ipom

229 Chapter 30 · Clinical Results After Open Mesh Repair

the hernia defect. But there is a vast difference between a midline hernia defect of 20 cm width and 5 cm length compared to a defect of 5 cm width and 20 cm length, though the total defect size is the same. Also, some surgical techniques open the complete scar of the previous incision, which results in a much larger defect than preoperatively described. Certainly, the total defect size is important, but the transverse diameter seems to be more relevant for the intraoperative intention to reach a tensionfree repair. Just recently, prognostic factors such as age, gender, consumption of nicotine, obesity, family history, wound contamination, and previous postoperative complications have been taken into account [6]. Under the aegis of the EHS a new attempt is on its way, but so far, no classification has reached its goal of international implementation. Another problem of comparing the existing data is the design of the follow-up period and investigation. Knowing that the incidence of incisional hernia formation shows a linear rise, the length of follow-up is of decisive significance. In the study of Luijendijk et al., the rate of recurrence after incisional hernia formation was 44% after suture repair and 24% after mesh repair [7]. The follow-up investigation of the same patient population by Burger et al. several years later revealed an increase in recurrence rate with a 10-year cumulative rate of recurrence of 63% after suture repair and 32% after mesh repair [8]. So even many years after hernia repair, there was still a steady rise in recurrence. To evaluate any technique in terms of recurrence, a follow-up of 2 years does not seem to be sufficient. Evaluation of the clinical results of the different repairs must consider early postoperative and late postoperative complications. Early postoperative complications include hematoma, seroma, and acute postoperative pain. Again, there is no international consensus on the definition of hematoma or seroma, detection by ultrasound or clinical investigation, or size (10 ml or 20 ml)? Pain is coming more and more into the focus of clinical research. But there is no standardised questionnaire being used internationally, so the existing data cannot really be compared. Infection is

30

also one of the major concerns in open incisional hernia repair, but there is usually no differentiation between superficial wound infection and deep mesh infection. Must a local erythema be considered an infection? Again, no definition has found international implementation. The same relates to late postoperative complications such as chronic pain, ileus, and fistula formation. Even the number of recurrences differs according to the method of follow-up investigation. In the Vypro I trial, the recurrences that occurred in Aachen were asymptomatic and detected only by ultrasound [9]. If the follow-up investigation had been done by telephone interview, these recurrences would have never been documented. It remains a comparison of apples with oranges, a situation that becomes obvious when one looks at the only two randomised controlled trials available on incisional hernia repair. In the study of Luijendijk et al., the mesh repair was performed in a retromuscular way, with a Marlex mesh and an overlap of 2 cm. The anterior fascia in front of the mesh was closed only when a tension-free repair could be achieved; in the other cases, a resorbable mesh was interposed, making this study a mixture of mesh augmentation and mesh bridging techniques [7]. The other study compared a large-pore lightweight mesh with three very different conventional meshes. In this international multicentre trial, the importance of a meticulous protocol can be observed: Crucial steps in the surgical procedure were left to each centre’s standard procedure, such as mesh fixation, technique for closing the anterior fascia, and the kind of suture material itself [9]. The available studies and their results are summarised in ⊡ Tables 30.1–30.3 [10–32]. A comparison of these clinical results of open mesh repair is possible only with limitations. In open mesh repair, the retromuscular mesh augmentation seems to show the best results with the least severe complications. A worldwide accepted and applicable classification is needed. Also, a differentiation between the different surgical procedures with a subdivision into augmentation and bridging techniques is urgently necessary. Only then is a comparison of clinical results in open incisional hernia repair possible and reasonable.

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Chapter 30 · Clinical Results After Open Mesh Repair

⊡ Table 30.1. Results of onlay repair (RCT randomised controlled trial) Authors

Year

Study design

n

Follow-up (months)

Compl. %

Inf. %

Expl.

Rec. %

Vestweber et al. [10]

1997

Retrospective

36

32

?

27.7

0

6.4

Chevrel [32]

1997

Retrospective

389

1–20 years

?

10.9

0

5.5

Leber et al. [11]

1998

Retrospective

118

80

>20

?

0

14.8

Rios et al. [12]

2001

Retrospective

246

77

26

17

0

17

Korenkov et al. [ 13]

2002

RCT, stopped

70

14

?

26

0

8

San Pio et al. [14]

2003

Retrospective

67

68

?

?

?

15

Machairas et al. [ 15]

2004

Retrospective

43

54

21

?

?

9

Langer et al. [16]

2005

Retrospective

14

116

32

?

?

14

Israelsson et al. [17]

2006

Retrospective

281

>12m

?

?

?

19.3

Licheri et al. [18]

2008

Retrospective

64

?

26.5

?

0

2/64

Kingsnorth et al. [19]

2008

Prospective

116

15.2

25

8.6

0

3.4

⊡ Table 30.2. Results of retromuscular repair (RCT randomised controlled trial)

30

Authors

Year

Study design

n

follow-up (months)

Compl.

Inf.

Expl.

Rec.

Schumpelick et al. [20]

1996

Retrospective

58

54

?

3.2%

0

7%

McLanahan et al. [21]

1997

Retrospective

106

24

18%

12%

0

3.5%

Ladurner et al. [22]

2001

Retrospective

57

6–33

11%

0

0

2%

Wright et al. [23]

2002

Retrospective

90

32

36%

10%

0

6%

Paajanen and Hermunen [24]

2004

Retrospective

84

36

19%

6%

0

4%

Conze et al. [9]

2005

RCT

165

24

?

17%

0

12%

Le et al. [25]

2005

Prospective

150

>5

?

9.3%

2

2%

Israelsson et al. [17]

2006

Retrospective

228

>12 m

?

?

?

7.3%

Kurzer et al. [26]

2008

Retrospective

125

95

?

1.6%

2

4%

⊡ Table 30.3. Results of open peritoneal onlay mesh repair Authors

Year

Study design

n

Follow-up (months)

Compl.

Inf.

Expl.

Rec.

Marchal et al. [27]

1999

Retrospective

128

48

26%

14%

3

16%

Millikan et al. [28]

2003

Prospective

102

28

6%

0%

0

0%

Heartsill et al. [29]

2005

Retrospective

81

30

>20%

16%

3

15%

Bernard et al. [30]

2007

Prospective

61

35

21%

10%

2

5%

Bingener et al. [31]

2007

Prospective

233

30

15%

6%

6

9%

231 Chapter 30 · Clinical Results After Open Mesh Repair

References 1. Höer J, Lawong G, Klinge U, Schumpelick V (2002) Factors influencing the development of incisional hernia. A retrospective study of 2,983 laparotomy patients over a period of 10 years Chirurg 73:474–480 2. Conze J, Junge K, Klinge U, Schumpelick V (2006) Evidenzbasierte laparoskopische Chirurgie–Narbenhernie. Viszeralchirurgie 41:246–252 3. Conze J, Klinge U, Schumpelick V (2005) Incisional hernia. Chirurg 76:897–909 4. Klinge U, Conze J, Krones CJ, Schumpelick V (2005) Incisional hernia: open techniques. World J Surg 29:1066–1072 5. Korenkov M, Paul A, Sauerland S, et al. (2001) Classification and surgical treatment of incisional hernia. Results of an experts’ meeting. Langenbecks Arch Surg 386:65-–73 6. Dietz UA, Hamelmann W, Winkler MS, Debus ES, Malafaia O, Czeczko NG, Thiede A, Kuhfuss I (2007) An alternative classification of incisional hernias enlisting morphology, body type and risk factors in the assessment of prognosis and tailoring of surgical technique. J Plast Reconstr Aesthet Surg 60:383–388 7. Luijendijk RW, Hop WC, van den Tol MP, de Lange DC, et al. (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–398 8. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004) Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–583 9. Conze J, Kingsnorth AN, Flament JB, Simmermacher R, Arlt G, Langer C, Schippers E, Hartley M, Schumpelick V (2005) Randomized clinical trial comparing lightweight composite mesh with polyester or polypropylene mesh for incisional hernia repair. Br J Surg 92:1488–1493 10. Vestweber KH, Lepique F, Haaf F, Horatz M, Rink A (1997) Mesh-plasty for recurrent abdominal wall hernias–results. Zentralbl Chir 122:885–888 11. Leber GE, Garb JL, Alexander AI, Reed WP (1998) Longterm complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378–382 12. Rios A, Rodriguez JM, Munitiz V, Alcaraz P, Pérez D, Parrilla P (2001) Factors that affect recurrence after incisional herniorrhaphy with prosthetic material. Eur J Surg 167:855–859 13. Korenkov M, Sauerland S, Arndt M, Bograd L, Neugebauer EA, Troidl H (2002) Randomized clinical trial of suture repair, polypropylene mesh or autodermal hernioplasty for incisional hernia. Br J Surg 89:50–56 14. San Pio JR, Damsgaard TE, Momsen O, Villadsen I, Larsen J (2003) Repair of giant incisional hernias with polypropylene mesh: a retrospective study. Scand J Plast Reconstr Surg Hand Surg 37:102–106 15. Machairas A, Misiakos EP, Liakakos T, Karatzas G (2004) Incisional hernioplasty with extraperitoneal onlay polyester mesh. Am Surg 70:726–729 16. Langer C, Liersch T, Kley C, Flosman M, Suss M, Siemer A, Becker H (2005) Twenty-five years of experience in incisi-

17.

18.

19.

20.

21.

22.

23.

24.

25. 26.

27.

28.

29.

30.

31.

32.

30

onal hernia surgery. A comparative retrospective study of 432 incisional hernia repairs. Chirurg 74:638–645 Israelsson LA, Smedberg S, Montgomery A, Nordin P, Spangen L (2006) Incisional hernia repair in Sweden 2002. Hernia 10:258–261 Licheri S, Erdas E, Pisano G, Garau A, Ghinami E, Pomata M (2008) Chevrel technique for midline incisional hernia: still an effective procedure. Hernia 12 (2):121-–126 Kingsnorth AN, Shahid MK, Valliattu AJ, Hadden RA, Porter CS (2008) Open onlay mesh repair for major abdominal wall hernias with selective use of components separation and fibrin sealant. World J Surg 32:26–30 Schumpelick V, Conze J, Klinge U (1996) Preperitoneal mesh-plasty in incisional hernia repair. A comparative retrospective study of 272 operated incisional hernias. Chirurg 67:1028–1035 McLanahan D, King LT, Weems C, Novotney M, Gibson K (1997) Retrorectus prosthetic mesh repair of midline abdominal hernia. Am J Surg 173:445–449 Ladurner R, Trupka A, Schmidbauer S, Hallfeldt K (2001) The use of an underlay polypropylene mesh in complicated incisional hernias: successful French surgical technique. Minerva Chir 56 :1111–1117 Wright BE, Niskanen BD, Peterson DJ, Ney AL, Odland MD, VanCamp J, Zera RT, Rodriguez JL (2002) Laparoscopic ventral hernia repair: are there comparative advantages over traditional methods of repair? Am Surg 68:291–295 Paajanen H, Hermunen H (2004) Long-term pain and recurrence after repair of ventral incisional hernias by open mesh: clinical and MRI study. Langenbecks Arch Surg 389:366–370 Le H, Bender JS (2005) Retrofascial mesh repair of ventral incisional hernias. Am J Surg 189:373–375 Kurzer M, Kark A, Selouk S, Belsham P (2008) Open mesh repair of incisional hernia using sublay technique: longterm follow-up. World J Surg 32:31–36 Marchal F, Brunaud L, Sebbag H, et al. (1999) Treatment of incisional hernias by placement of an intraperitoneal prosthesis: a series of 128 patients. Hernia 3:141–147 Millikan KW, Baptista M, Amin B, Deziel DJ, Doolas A (2003) Intraperitoneal underlay ventral hernia repair utilizing bilayer expanded polytetrafluoroethylene and polypropylene mesh. Am Surg 69:287–291 Heartsill L, Richards ML, Arfai N, Lee A, Bingener-Casey J, Schwesinger WH, Sirinek KR (2005) Open Rives-Stoppa ventral hernia repair made simple and successful but not for everyone. Hernia 9:162–166 Bernard C, Polliand C, Mutelica L, Champault G (2007) Repair of giant incisional abdominal wall hernias using open intraperitoneal mesh. Hernia 11:315–320 Bingener J, Buck L, Richards M, Michalek J, Schwesinger W, Sirinek K (2007) Long-term outcomes in laparoscopic vs open ventral hernia repair. Arch Surg 142:562–567 Chevrel JP, Rath AM (1997) The use of fibrin glues in the surgical treatment of incisional hernias. Hernia 1:9–14

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Chapter 30 · Clinical Results After Open Mesh Repair

Discussion Bellows: Can you comment on the use of allogenic mesh material for instance alloderm? Schumpelick: We have never used biological meshes. Why should I use such meshes? Deysine: I totally agree that we need a better classification of incision hernias.

30

31

Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair D. Berger, M. Bientzle

234

Chapter 31 · Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair

Introduction Laparoscopic repair of incisional hernias is gaining increasing popularity because it has some advantages compared to open techniques [1, 2]. The frequency of infectious complications, for example, is significantly reduced. Previous studies also demonstrated reduced pain after laparoscopic incisional hernia repair, a finding that has also been pointed out in a very recent review [3–7]. In contrast, Pierce et al. clearly showed that early postoperative pain is a major issue [1]. The frequency of prolonged pain was nearly 2% in the laparoscopic group compared with 0.9% in the open group. A recent study found dissatisfying pain in 9% in the long run [8]. In our preliminary study, all patients who were laparoscopically treated for an incisional hernia were followed up in the early postoperative period using a visual analogue scale. Long-term follow-up was performed using a pain score similar to those used in other studies dealing with chronic pain.

Patients and Methods

31

Since 2002, all patients treated for incisional hernias have been prospectively followed up in the early postoperative period with a visual analogue scale ranging from 0 to 10. The patients are studied twice a day in reclining and upright positions until leaving the hospital. Our preliminary evaluation comprised 100 patients. Fifty patients had a mesh derived from expanded polytetrafluoroethylene (e-PTFE), and starting in May 2004, 50 patients received a mesh derived from polyvinylidene fluoride (PVDF), Dynamesh IPOM. The distribution of age, gender, and surgical parameters such as hernia size were not different between the groups. A further clinical examination was performed after 1, 3, 6, 12 months and yearly thereafter using a simplified pain score, which is shown in ⊡ Table 31.1.

Surgical Technique The surgical technique did not differ over the years. Routinely, the whole abdominal scar was covered by

⊡ Table 31.1. Classification of long-lasting postoperative pain 0 1 2 3 4

No pain at all, very satisfied Sometimes minimal pain during work, satisfied Sometimes moderate pain during work, still satisfied Often annoying pain during work, dissatisfied Strong pain at rest, very dissatisfied

the mesh, not just the obvious fascial defect. After complete adhesiolysis of the whole abdominal wall, the falciform ligament was dissected in cases with hernias or incisions reaching the upper abdomen. In patients with hernias or incisions of the lower abdomen, the fatty tissue between the plicae mediales was dissected to open the Retzius space. The meshes were fixed with six stay sutures at the corners and in the midline in the longest extension of the mesh. Furthermore, spiral tacks were used every 3–4 cm. For covering the lower abdomen, the mesh was fixed with spiral tacks at the pubic bone and the symphysis. In cases of upper abdominal hernias, the tacks were placed in the rips at the costal arch. Diclofenac and metamizole were routinely given in the postoperative period. In some cases, piritramide was added via a patient-controlled analgesia pump. Statistical analysis was done using analysis of variance tests for repeated measurements.

Results As outlined above, the two groups did not differ concerning demographic or surgical parameters. As shown in ⊡ Fig. 31.1, the patients suffered from very strong pain during the first 3 days, especially when in an upright position. The pain scores slowly decreased from a median of 7 the morning of the first postoperative day to 4 and 3 at days 3 and 4, respectively. However, there is a significant difference between the groups: Patients treated with DynaMesh IPOM showed significantly lower pain scores for 5 days than patients who received an ePTFE-derived mesh, as shown by analysis of variance testing for repeated measurements. No further correlation of pain with other parameters–such as age, gender,

235 Chapter 31 · Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair

31

8

6

4

2

0 d1ml d1ms d1el d1es d2ml d2ms d2el d2es d3ml d3ms d3el d3es d4ml d4ms d4el d4es d5ml d5ms d5el d5es

body mass index, mesh size, hernia size, duration of the procedure itself, amount and intensity of adhesions, or number of previous procedures–could be established. Chronic pain was observed only during the first 3 months of the observation period. The median pain score after 4 weeks was 1.5, which indicates minimal to moderate pain during work. Six patients were dissatisfied at that time point. Only one patient was still dissatisfied after 3 months, but the problems finally resolved without further treatment. Any correlation of chronic or persisting pain with clinical parameters could not be established because of the low number of patients. For the same reason, a differentiation between the two groups did not seem to be appropriate.

Discussion It is usually believed that a main advantage of laparoscopic procedures is reduced pain in the early

⊡ Fig. 31.1. Postoperative visual analogue scale (VAS) scores. Box plots are demonstrated. The x-axis shows the time course between day 1 and day 5, given as d1m (m morning) to d5e (e evening). The different time points differentiate between the reclining (l) and upright patient positions (s). The y-axis shows the VAS level

postoperative period, which has been proven for inguinal hernia repair [9–11]. Our own clinical experience, however, showed that after laparoscopic incisional hernia repair, the patients suffered from severe pain. The early literature described a reduced need for narcotics after laparoscopic repairs compared with conventional procedures [3–6]. Even today, a review of incisional hernia repair concluded that laparoscopy is superior compared with open techniques in terms of postoperative pain [7]. However, Pierce et al. [1] described in their analysis that »unlike most other laparoscopic procedures where incisional pain is typically minimal and relatively short lived, laparoscopic incisional hernia repair is associated with substantially more pain in the postoperative period because of the methods of mesh fixation.« Our data clearly show that our patients experienced annoying pain in the early postoperative period. The use of an elastic mesh, the properties of which are comparable to the human abdominal

236

31

Chapter 31 · Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair

wall [12], is associated with significantly reduced pain scores. For inguinal hernias, it is known that the level of pain in the early postoperative period strongly correlates with chronic pain problems [13], thus supporting the recommendation that elastic meshes should be preferred. A correlation between acute and chronic pain could not be established in our series. The number of patients studied up to now is probably too small. Some major prospective studies and reviews have observed prolonged or chronic pain in up to 9% of patients [1, 2, 8]. Unfortunately, a definition of prolonged pain is not generally given that would enable comparison among different publications. The prolonged pain is usually explained by the fixation devices, mostly transfascial sutures and tacks [4]. Local anaesthesia is recommended, followed by removal of stay sutures or tacks in otherwise untreatable cases [4]. In one series with 1.6% persistent pain, the removal of tacks or stay sutures did abolish the pain in three of six patients [14]. The success rate is not given in any other series. In our series, chronic pain resolved spontaneously after conservative treatment in all cases. However, one patient was significantly restricted in his daily activities for almost 6 months. In conclusion, laparoscopic repair of incisional hernias is a painful treatment needing subsequent analgesic postoperative therapy. Dynamesh IPOM, which exhibits a physiological elasticity [12], significantly reduces the pain level in the early postoperative period. The number of patients studied does not allow any conclusion about the nature of chronic pain. An association between acute and chronic pain could not be established for laparoscopic incisional hernia repair.

References 1. Pierce RA, Spitler JA, Frisella MM, Matthews BD, Brunt LM (2007) Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual. Surg Endosc 21:378–386 2. Carlson MA, Frantzides CT, Shostrom VK, Laguna LE (2008) Minimally invasive ventral herniorrhaphy: an analysis of 6,266 published cases. Hernia 12:9–22 3. Carbajo MA, Martin DOJ, Blanco JI, de la Cuesta C, Toledano M, Martin F, Vaquero C, Inglada L (1999) Laparoscopic treatment vs open surgery in the solution of major

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

incisional and abdominal wall hernias with mesh. Surg Endosc 13:250–252 Heniford BT, Park A, Park AF, et al. (2003) Laparoscopic repair of ventral hernias: nine years’ experience with 850 consecutive hernias. Ann Surg 238:391–400 LeBlanc KA, Booth WV, Whitaker JM, Bellanger DE (2001) Laparoscopic incisional and ventral herniorraphy: our initial 100 patients. Hernia 5:41–45 Park A, Birch DW, Lovrics P (1998) Laparoscopic and open incisional hernia repair: a comparison study. Surgery 124:816–821 Misiakos EP, Machairas A, Patapis P, Liakakos T (2008) Laparoscopic ventral hernia repair: pros and cons compared with open hernia repair. JSLS 12:117–125 Stickel M, Rentsch M, Clevert DA, Hernandez-Richter T, Jauch KW, Lohe F, Angele MK (2007) Laparoscopic mesh repair of incisional hernia: an alternative to the conventional open repair? Hernia 11:217–222 Bringman S, Ramel S, Heikkinen TJ, Englund T, Westman B, Anderberg B (2003) Tension-free inguinal hernia repair: TEP versus mesh-plug versus Lichtenstein: a prospective randomized controlled trial. Ann Surg 237:142–147 Collaboration EH (2000) Laparoscopic compared with open methods of groin hernia repair: systematic review of randomized controlled trials. Br J Surg 87:860–867 Grant AM (2002) Laparoscopic versus open groin hernia repair: meta-analysis of randomised trials based on individual patient data. Hernia 6:2–10 Junge K, Klinge U, Prescher A, Giboni P, Niewiera M, Schumpelick V (2001) Elasticity of the anterior abdominal wall and impact for reparation of incisional hernias using mesh implants. Hernia 5:113–118 Callesen T, Bech K, Kehlet H (1999) Prospective study of chronic pain after groin hernia repair. Br J Surg 86:1528– 1531 Wassenaar EB, Raymakers JT, Rakic S (2007) Removal of transabdominal sutures for chronic pain after laparoscopic ventral and incisional hernia repair. Surg Laparosc Endosc Percutan Tech 17:514–516

Discussion Flament: When you report about the hernia size

you spoke only about the diameter. But there is still another dimension: The volume of herniated bowel. Therefore we do a CT-scan before the operation to measure the volume of the bowel in the abdominal cavity and the volume of the herniated bowel to exactly estimate the size of the hernia. Berger: Your approach is very sophisticated and would be the best of course. Schippers: You use a minimal invasive approach and you use a bridging technique and you have a

237 Chapter 31 · Acute and Chronic Pain After Laparoscopic Incisional Hernia Repair

long period of postoperative pain. What is your explanation of this pain? Berger: I can only speculate. I think that a fixation trough the peritoneum is the main problem. Chowbey: A secret of good result in laparoscopic hernia repair depends on the selection of patients. In what cases laparoscopic hernia repair can be done and what cases it cannot be done laparoscopically? Another thing is the number of used tackers for the mesh fixation. If you use too much tackers the risk of pain raises. Berger: I agree concerning your remark about the number of tackers. However, I never found a recommendation of the number of tackers used in study dealing with laparoscopic hernia repair. Of course there are some hernias that cannot be repaired laparoscopically. If we cannot reach an adequate overlap – at least five centimeters on both sites – we do an open procedure.

31

32

Effect of Nerve Identification on the Rate of Postoperative Chronic Pain Following Inguinal Hernia Surgery S. Alfieri, D. Di Miceli, R. Menghi, G. Quero, C. Cina, G. B. Doglietto

240

Chapter 32 · Effect of Nerve Identification on the Rate of Postoperative Chronic Pain Following Inguinal Hernia Surgery

Introduction The ilioinguinal nerve, iliohypogastric nerve, and inguinal segment of the genital branch of the genitofemoral nerve all cross the inguinal channel and consequently are vulnerable to injury. But if they are injured, is there any evidence that they can produce pain syndromes? Should a suspected injured nerve or a nerve in the way of repair be cut (divided), resected, or left in place? Should the cut end of the nerve be left exposed or buried in the muscle? Much controversy still exists regarding how to treat these three inguinal nerves during hernia repair, with many published studies showing contrasting results. Consequently, it is right to wonder about the following: ▬ Do the inguinal nerves really play a role in the genesis of postherniorrhaphy inguinodynia and orchialgia? ▬ Is there any scientific evidence today that chronic pain is related to the different treatment reserved for the three inguinal nerves during hernia repair?

32

In trying to give scientific answers to these questions, we have evaluated not only the levels of evidence (LE) and grades of recommendation (GR) for every published study in this field, but we also read each paper in its entirety and evaluated its statistical validity and the terminology used. It is not surprising that we discovered some discrepancies between the data found in the article and the conclusions extrapolated by systematic reviews (LE, 1a; GR, A).

Definitions and Terminology An important issue is the need to provide uniform terminology to be used in this field. In fact, the terms division, resection, dissection, transection, section, and neurectomy were often used and reported incorrectly in the literature, which influenced and distorted the real results of the studies, with important and practical implications involving the treatment of chronic pain [1]. A clear example of this is demonstrated by the wrong interpretation of the study by Picchio et al.

[2], which is often cited as demonstrating that pain is not affected by elective division of the ilioinguinal nerve. However, when reading the whole paper, it is possible to learn that the authors actually performed a neurectomy (dividing the nerve lateral to the internal ring) instead of a simple division of the nerve in the operative field. Consequently, the results of this paper not only have often been distorted but also may give the erroneous message that the nerves may be sectioned during operation at any level of the inguinal canal without any consequence [3]. With the aim of providing uniform terminology, the international consensus conference held in Rome in April 2008 decided to recommend the following nomenclature: ▬ Cutting or dividing a nerve means interrupting the continuation of a nerve. It is appropriate to mention the way the cut ends were handled, such as by ligation, cauterisation, or nothing. ▬ Resection of a nerve or neurectomy means removing the segment of a nerve along the inguinal canal. It is recommended to cut the proximal end up to its intramuscular part. It is appropriate to mention the handling of the cut ends and the proximal and distal parts of the section.

Is There Any Correlation Between Chronic Pain and Identifying vs. Not Identifying the Three Inguinal Nerves? Although it has been demonstrated that preoperative identification of all inguinal nerves is almost always possible [4], the majority of surgeons continue to not detect them, as recently emphasised and confirmed for the iliohypogastric nerve (detected in only 32% of cases) and for the genital branch of the genitofemoral nerve (detected in only 36% of cases) [5]. In fact, the vast majority of the studies report data for only one nerve (generally the ilioinguinal nerve, probably because is the easiest to recognise during hernia repair) without giving any data concerning the other two nerves, neglecting the fact that all three nerves contribute to the sensory innervation of the groin.

241 Chapter 32 · Effect of Nerve Identification on the Rate of Postoperative Chronic Pain

An Italian prospective multicentre study of 973 cases and a French single-centre study of 1,332 cases are the only two published studies presenting results for all three inguinal nerves (2,305 cases altogether) with a long follow-up period (1–5 years) [6, 7]. Both studies concluded that identification and preservation of all three inguinal nerves (which occurred in 924 patients considering the two papers together) during open inguinal hernia repairs (with or without mesh) reduces chronic incapacitating groin pain to less than 1%; the mean incidence of chronic pain was 0.8% (range 0–1.6%). The Italian study also demonstrated that the risk of developing inguinal pain increased with the number of nerves concomitantly undetected. Likewise, the division of nerves strongly correlated with the presence of chronic pain [7]. According to the data in the literature, we can conclude that identifying and protecting the three inguinal nerves decreases the risk of postoperative severe chronic pain.

Should the Identified Nerve Be Preserved, Divided, or Resected (Neurectomy)? All of the published studies report data concerning division versus preservation of only a single nerve, without giving any data concerning the other two nerves. In all of these papers, the results are distorted because the nerves not considered could have been unintentionally divided or injured during operation. For these reasons, chronic pain could be generated [8]. The studies by Ravichandran et al. [9] (LE, 2b; GR, B) and Mui et al. [10] (LE, 1b; GR, A) report results of preservation versus neurectomy of only one single nerve, and these results are also limited by very small sample sizes, with only 20 patients and 50 patients in each arm. Therefore, these studies do not have substantial statistical power compared with the study of Dittrik et al. [11] (LE, 2b; GR, B), which also did not have homogeneous distribution between the two arms (66 patients versus 24 patients). In these cases, no conclusions can be evaluated, even if some studies are prospective and ran-

32

domised and apparently have the highest recommendation grade [3]. These underpowered studies are sometimes used in meta-analyses or reviews by calculating a pooled mean percentage by means of a randomised model to reach some conclusions. However, data coming out of such a model that uses small studies are completely distorted. Picchio et al. [2] (LE, 1b; GR, A) reported that pain is not affected by elective division of the ilioinguinal nerve. However, by reading the whole paper (with 400 patients in each arm), one discovers that the author actually performed more of a neurectomy (dividing the nerve lateral to the internal ring) than a simple division of the nerve in the operative field. The results of this paper have been often distorted; in fact, some authors wrongly reported that the nerve was »divided,« and others stated that the nerve was dissected, without explaining that even if Picchio et al. did not report where the nerve was divided caudally, they divided the nerve lateral to the internal ring. Merely concluding that division/dissection of the ilioinguinal nerve does not increase or reduce the risk of chronic pain not only distorts the researchers’ results, but, more importantly, it may give the erroneous message that the nerves may be sectioned during operation at any level of the inguinal canal without any consequence. Picchio et al. [2] (LE, 1b; GR, A) report that pain is not affected by elective neurectomy (according to the new nomenclature of the consensus conference) of the ilioinguinal nerve, and Pappalardo et al. [12] report this for iliohypogastric neurectomy. According to the literature, we can conclude that identification and protection of all three nerves during open inguinal hernia repair (with or without mesh) reduces the risk of chronic incapacitating pain to less than 1%.

Should the Identified Nerve Be Isolated or Left in its Natural Bed Without Manipulation, Taking Care To Not Remove the Covering Fascia of the Nerve? No published data are available regarding manipulation versus no manipulation of a preserved nerve. However, considering the anatomical stud-

242

Chapter 32 · Effect of Nerve Identification on the Rate of Postoperative Chronic Pain Following Inguinal Hernia Surgery

ies [4], we suggest (LE, 5; GR, D) leaving the the nerves in their natural bed as much as possible and not removing the covering fascia.

Should a Suspected Injured Nerve or a Nerve in the Way of Repair Be Saved by All Means or Resected?

32

The current literature is inconsistent concerning this point. Opinions differ considerably, but no published data are actually available. Some authors emphasise that when an injury has occurred, the intramuscular portion of the nerve must be resected, stating that merely dividing the nerve at the point of its emergence is inadequate [3, 5]. These data are supported by the increasing success rates of pain relief with extended versus standard neurectomy procedures, as obtained by Amid et al. [5] for patients with chronic postherniorrhaphy pain (LE, 4; GR, C) and by Alfieri et al. [6], who reported that the increased risk of developing chronic pain with the number of nerves divided could be explained by the fact that resection of the unidentified nerve has generally been performed distal to its origin; this leaves the site of the injured nerve intact–and able to continue to generate a pain signal–and exposes it to neuroma formation (LE, 5; GR, D). At the same time, there is no scientific evidence that the cut end of the nerve should be left exposed or buried in the muscle. While we await definitive results in the literature, it is reasonable to remove a suspected injured nerve or a nerve in the way of the repair during any type of repair and to implant the proximal cut end in the muscle (LE, 5; GR, D).

How Can the Inguinal Segment of the Genital Branch of the Genitofemoral Nerve Be Identified and Protected During the Open Procedure? Identifying and protecting the inguinal segment of the genital branch nerve during hernia repair is not difficult. It can be recognised, identifying and keeping the external spermatic vein (the socalled blue line) with the cord. However, the geni-

tal branch nerve can be damaged if inadvertently sectioned, entrapped, or secured (for example, if a continuous suture is introduced along the inguinal ligament), or it can be injured if the external spermatic vessels are divided to skeletonise the cord without its identification.

Should the Cremasteric Layer Be Saved or Resected? No published data are available in the literature. However, it is advisable for hernia mesh repair to save the cremasteric layer to reduce the risk of ilioinguinal and genital branch nerve damage and thus avoid possible incapacitating and chronic postoperative pain (LE, 5; GR, D).

Should the Cut Ends of the Nerve Be Left Alone, Ligated, or Cauterised? No scientific data are reported in the literature concerning the treatment of the cut ends of the nerves.

When Glue Is Used, Should We Still Identify and Protect the Nerves? No data are present in the literature concerning whether nerves should be identified and protected even if glue is used. However, it is reasonable to consider that nerves should be identified and protected in any case (LE, 5; GR, D).

Is There Convincing Evidence that Prophylactic Division or Resection of Nerves During Hernia Repair Will Reduce the Rate of Chronic Pain? Three randomised trials examined the effect of prophylactic neurectomy on chronic pain [2, 9, 10]. In all of the trials, the ilioinguinal nerve was either divided or partially resected and the patients assessed for pain, numbness, and touch and pain sensation at 1, 6, and 12 months. None of the

243 Chapter 32 · Effect of Nerve Identification on the Rate of Postoperative Chronic Pain

studies found differences in pain or numbness, although one found significant improvements in activities such as cycling and walking in favour of the nerve division group. In a prospective multicentre study of 973 patients undergoing inguinal hernia repair in which all nerves were identified [6], nerve division was associated with an increased risk of moderate to severe pain. According to the published results in the literature, we can conclude that there is no evidence that prophylactic neurectomy reduces chronic pain after inguinal hernia repair. On the contrary, indirect evidence suggests that identification and preservation of all nerves may be beneficial. However, further studies addressing this issue are required.

Conclusions The data would suggest that if one or more nerves is not detected during surgery, it is possible that they could be inadvertently sectioned, entrapped, or secured (for example, if a continuous suture is introduced along the inguinal ligament), or they could be injured (such as if the external spermatic vessels are divided to skeletonise the cord). It should not be forgotten that nerves are most often injured when the surgeon is unaware of their location and course, or when he or she fails to recognise them during surgery. Caution is stressed when teaching this common procedure to resident physicians. Finally, it is very important to develop a uniform terminology for this field in order to better analyse and compare the studies and thereby avoid giving wrong messages to the community.

4.

5.

6.

7.

8.

9.

10.

11.

12.

32

preserve the 3 inguinal nerves during hernia repair? Ann Surg 2008; 247(6) Wijsmuller, A.R., et al. Nerve-identifying inguinal hernia repair: a surgical anatomical study. World J Surg 2007; 31(2):414–420; discussion 421–422 Amid P.K., Hiatt J.R. New understanding of the causes and surgical treatment of postherniorrhaphy inguinodynia and orchialgia. J Am Coll Surg 2007; 205(2):381–385 Alfieri S., Rotondi F., Di GiorgioA., Fumagalli U., Salzano A., Di Miceli D., Ridolfini M.P., Sgagari A., Doglietto G.B., Groin Pain Trial Group. Influence of preservation versus division of ilioinguinal, iliohypogastric, and genital nerves during open mesh herniorrhaphy: prospective multicentric study of chronic pain. Ann Surg 2006; 243(4):553–558 Izard G., Gailleton R., Randrianasolo S., Houry R. Treatment of inguinal hernias by McVay’s technique in a series of 1332 cases. Ann Chir 1996; 50(9):755–756 Alfieri S., Di Miceli D., Doglietto G.B. Prophylactic ilioinguinal neurectomy in open inguinal hernia repair. Ann Surg 2007; 245(4):663 Ravichandran D., Kalambe B.G., Pain J.A. Pilot randomized controlled study of preservation or division of ilioinguinal nerve in open mesh repair of inguinal hernia. Br J Surg 2000; 87(9):1166–1167 Mui W.L., Ng C.S., Fung T.M., Cheung F.K., Wong C.M., Ma T.H., Bn M.Y., Ng E.K. Prophylactic ilioinguinal neurectomy in open ilioinguinal repair: a double-blind randomized controlled trial. Ann Surg 2006; 244(1):27–33 Dittrick G.W., Ridl K., Kuhn J.A., McCarty T.M. Routine ilioinguinal nerve excision in inguinal hernia repairs. Am J Surg 2004; 188(6):736–740 Pappalardo G., Frattaroli F.M., Mongardini M., Salvi P.F., Lombradi A., Conte A.M., Arezzo M.F. Neurectomy to prevent persistent pain after inguinal herniorrhaphy: a prospective study using objective criteria to assess pain. World J Surg 2007; 31(5):1081–1086

Discussion Amid: To present the results of the consensus con-

ference in ten minutes is not enough time. Schippers: One of your recommendations was to

References 1. Alfieri S., Di Miceli D., Doglietto G.B. Re: nerve management during open hernia repair Br J Surg 2007; 94(7):914 2. Picchio M., Palimento D., Attanasio U., Matarazzo P.F., Bambini C., Caliendo A. Randomized controlled trial of preservation or elective division of ilioinguinal nerve on open inguinal hernia repair with polypropylene mesh. Arch Surg 2004; 139(7):755–758 3. Alfieri S. Is there a consensus concerning the relationship between post-operative chronic pain and treatment to

leave the nerve where it was. You recommend not touching the nerve anyway. But with this recommendation you have problems to do the Shouldice repair properly. Alfieri: But this is just a personal comment and the evidence level is very low.

33

Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair: A Report from the SMIL Study Group A. Montgomery

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Chapter 33 · Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair

Introduction

33

Hernia recurrence used to be the main outcome measurement when reporting on the results of inguinal hernia surgery. Today the problem of recurrence is limited as a result of standardised mesh techniques. A recurrence does not always result in a problem for the patient, and if it does, it can usually be resolved after a new repair. Chronic pain and discomfort is considered to be the most important outcome measure of inguinal hernia repair. Chronic pain and discomfort are often difficult to handle, and even small constant problems can be an annoying reminder to the patient of the former hernia. This is why the indications for surgery must be very strict. The study on »watchful waiting« in patients with very mild symptoms is therefore of great importance in this respect [1]. Chronic pain is commonly defined as pain or discomfort that lasts for more than 3 months postoperatively. The incidence of chronic pain varies widely in different publications: between 0% and 75% in open mesh repair and between 0% and 29% after laparoscopic hernia repair [2–4]. Most of the problems are described as mild discomfort. Pain affecting daily activities has been reported to be as high as 5–6% [5, 6]. Some authors claim that mesh repair results in less chronic pain than nonmesh repair and that laparoscopic repair is more favourable than open mesh repair in this regard [7–9]. The lack of description and definition of postherniorrhaphy pain and discomfort is a problem, making it impossible to compare the results from different studies. Professor Kehlet from Denmark and his colleagues have called for »uniform assessment on postherniorrhaphy pain« to facilitate interpretation of further studies [10]. Such assessment is complicated, though, and must take many aspects into account. Fränneby et al. have attempted this by constructing an 18-question form, a specific inguinal pain questionnaire called the IPQ, which has been validated [11]. Another problem is that the patients who are included in different studies often show a mixture of different techniques for both open and laparoscopic repair and for primary and recurrent hernias, and there are variations in the length of follow-up. An additional complication is the number of patient

drop-outs for the long-term follow-up. The method of follow-up is also important. A clinical examination and a standardised protocol are seldom used. Several large randomised studies comparing laparoscopic to open repair for primary unilateral inguinal hernias with a long follow-up have been performed, with a primary end point of recurrence rate. Most of these studies were initiated during the 1990s. Chronic pain is reported as a secondary end point [12–15]. The SMIL study group described below has reported on some large randomised studies. This chapter mainly concentrates on the discussion of chronic pain and discomfort from the first study–SMIL I.

SMIL Study Group The Swedish Multicentre Trial of Inguinal Hernia Repair by Laparoscopy study group (SMIL for short) was formed in 1993 to evaluate the possible benefit of laparoscopic repair compared with open techniques. The aim was to conduct well-designed large multicentre randomised controlled trials within general surgeon practices in the normal clinical setting. The group has conducted two large studies comparing laparoscopic and open repair. SMIL I started in 1993 and compares transabdominal preperitoneal (TAPP) repair with Shouldice repair for primary inguinal hernias. This study has resulted in three publications [16–18]. SMIL II was the second large study, initiated in 1996 as a result of the development of both the laparoscopic and the open inguinal hernia repair techniques. At that time, the totally extraperitoneal (TEP) technique had been introduced, avoiding the transabdominal approach. At the same time, larger meshes were recommended for a larger overlap of the hernial orifices, with the aim of reducing the risk of a recurrence. In this study, TEP was compared with the open mesh technique of Lichtenstein, which was the gold standard at that time. This study has resulted in two publications, and another two have been submitted [19, 20]. The third study is an early study of the use of small meshes in the laparoscopic group, comparing TAPP with Lichtenstein for recurrent hernias. This has resulted in one publication [21].

33

247 Chapter 33 · Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair

All three studies were designed with a primary end point of recurrence after 5 years.

TAPP vs. Shouldice–SMIL I The TAPP technique was compared to the open Shouldice operation in primary inguinal hernias in male patients between 30 and 70 years of age. A total of 25 board-certified surgeons using either tech-

Have you noticed signs of recurrence of your hernia (a bulge in the operated groin)? Yes

No

Do you have any other complaints? Yes

No

nique from seven different hospitals participated in the study. Both preoperative and perioperative variables were recorded, and short-term outcomes regarding pain were recorded on a visual analogue scale (VAS) daily during the first week. The patient’s functional status was also recorded. A clinical exam was performed at 1 and 5 years postoperatively, looking for recurrences and complaints, and a written questionnaire was answered at 1, 2, 3, and 5 years. The patient was asked to describe his experience of any discomfort after the operation according to the form depicted in ⊡ Fig. 33.1. In cases of suspected recurrence or severe complaints, the patient was examined clinically. Complaints were graded according to the definitions of discomfort described in ⊡ Fig. 33.2. Two independent and blinded observers performed the grading. A consensus discussion was held when opinions differed.

If yes, describe them here.

Results

⊡ Fig. 33.1. Form used by the patient to describe complaints after inguinal hernia surgery

Mild:

Occasional discomfort or pain that does not interfere with daily life

Moderate: Occasional discomfort or pain that interferes with daily life Severe:

Daily discomfort and pain that interferes with daily life

⊡ Fig. 33.2. Definitions of discomfort

A total of 1,068 patients were operated on within the study. Patient characteristics were similar in the two groups. A total of 867 patients (81.2%) were eligible for analysis after 5 years. Levels of discomfort and pain in the two groups at the different time points are reported in ⊡ Table 33.1. The total percentage of patients who experienced discomfort of any kind was 8.5% in the TAPP group and 11.4% in the Shouldice group, with no significant difference between the groups. Although discomfort was usually mild, it was severe in 0.2% of the laparoscopic group and 0.7% of the open repair group. Severe pain the first postoperative week was the only risk factor for late discomfort in the Shouldice group [odds ratio (OR) 2.25, P=0.022].

⊡ Table 33.1. Grade of discomfort at different time points in the SMIL I study (TAPP transabdominal preperitoneal) 1 Year

2 years

3 years

5 years

Tapp

Open

Tapp

Open

Tapp

Open

Tapp

Open

Mild

9.4

10.5

8.9

13.4

9.2

10.6

5.5

7.9

Moderate

3.1

3.4

2.2

2.8

2.3

3.8

2.8

2.8

Severe

0.2

0

0

0.2

0

0

0.2

0.7

Total

12.7

13.9

11.2

16.4

11.5

14.4

8.5

11.4

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Chapter 33 · Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair

No other risk factor for late discomfort was found in either group.

Discomfort in SMIL I Compared with SMIL II The SMIL II study had the same protocol as SMIL I, but the operating techniques were different, as described above. A total of 1,370 patients were operated on, and 1,275 had a 5-year follow-up. Having the same protocol enables more appropriate comparison of all four techniques regarding postoperative pain. Discomfort at 1, 2, 3, and 5 years is shown in ⊡ Fig. 33.3. There was a statistically difference between Shouldice and TAPP only at the 2-year point. There was a statistically significant difference between Lichtenstein and TEP at all time points in favour of the TEP technique. The risk of having chronic pain was approximately twice as high in the Lichtenstein group as in the other groups at all time points; almost 20% in the Lichtenstein group reported discomfort at all time points.

%

*

The number of patients classified as having severe pain was low in both groups. Patients with severe or moderate pain were therefore merged, creating the moderate/severe pain group. The results are demonstrated in ⊡ Fig. 33.4. There was a statistically significant trend over time for a decrease in frequency of moderate/severe chronic pain for Lichtenstein repair but not for the other techniques. In a multivariable analysis, risk factors for chronic pain in the TEP group were impairment in the physical test after 1 week, longer recovery time than the median, and weight below the 3rd quartile. For the Lichtenstein group, the risk factor was pronounced postoperative pain.

Discussion Discomfort and chronic pain was not the primary end point in any of the large randomised studies comparing laparoscopic and open hernia inguinal hernia repair. Altogether, there are four studies on

*

*

*

20

33

*

18 16 14

TAPP Shouldice TEP Lichtenstein

12 10 8 6 4 2 0 1

2

3

5

years

⊡ Fig. 33.3. Total amount of discomfort for different techniques at different time points in the SMIL I and II studies. Significant differences between groups are indicated by an asterisk (*)

249 Chapter 33 · Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair

chronic pain besides the SMIL studies, including more than 400 patients [12–15]. There are huge differences in these studies in follow-up time, which varies between 1 and 5 years. There are also huge differences in the percentage of attendees at the last follow-up, varying between 61% and 96%. The definition of chronic pain is also difficult to compare among the studies, but all studies report less pain with the laparoscopic technique. However, this varies in the studies, too, being between 0% and 18% for the laparoscopic technique and between 1% and 20% for the open techniques. The overall percentage of chronic pain at 5 years in the SMIL I study was 8.5% for TAPP and 11.4% for Shouldice. This difference is, however, not significant. In SMIL II there was a bigger difference between chronic pain in the TEP-operated and Lichtenstein groups–9% and 19%, respectively. However, the high attendance, with clinical examination and a standardised questionnaire, at 5-year follow-up in both SMIL studies is one of the SMIL studies’ strengths. A heavy polypropylene mesh was fixated using a stapling device in both the TAPP and TEP

33

procedures. The same mesh was used for the Lichtenstein operation. In recent research, anchoring of the mesh has been discussed as one cause of chronic pain. Several randomised studies have been performed on different fixation techniques, showing advantages for the nonfixated or glued mesh in endoscopic methods [22–25]. The advantage of less pain by using a low-weight mesh with large pores has also been discussed [26, 26]. All in all, the endoscopic preperitoneal technique seems to be more favourable for patients from the aspect of preventing chronic pain and discomfort. Development of new meshes and avoidance of fixation might favour the patients even further.

References 1. Fitzgibbons RJ, Giobbie-Hurder A et al. (2006) Watchful waiting vs repair of inguinal hernia in minimally symptomatic men. A randomized clinical trial. JAMA 295:285– 292 2. Nienhuijs SW, van Oort I, Keemers-Gels ME, Strobbe LJA, Rosman C. (2005) Randomized clinical trial comparing

% 20 18 16 14 TAPP Shouldice TEP Lichtenstein

12 10

*

8

*

6 4 2 0 1

2

3

5

years

⊡ Fig. 33.4. Moderate or severe discomfort for different techniques at different time points in the SMIL I and II studies. Significant differences between groups are indicated by an asterisk (*)

250

3.

4.

5.

6.

7.

8.

9.

10.

11.

33 12.

13.

14.

15.

Chapter 33 · Discomfort 5 Years After Laparoscopic and Shouldice Inguinal Hernia Repair

the Prolene Hernia System, mesh plug repair and Lichtenstein method for open inguinal hernia repair. Br J Surg 92:33–38 Poolban AS, Bruce J, Smith WC, King PM, Krukowski ZH, Chambers WA. (2003) A review of chronic pain after inguinal herniorrhaphy. Clin J Pain 19(1):48–54 PageB, Paterson C, Young D, O´Dwyer PJ. (2002) Pain from primary inguinal hernia and the effect of repair on pain. Br J Surg 89(10):1315–1318 Kalliomäki ML, Sandblom G, Gunnarsson U, Gordh T. (2009) Persistent pain after groin hernia surgery: a qualitative analysis of pain and its consequences for quality of life. Acta Anaesthesiol Scand 53(2):236-246 Fränneby U, Sandblom G, Nordin P, Nyrén O, Gunnarsson U. (2006) Risk factors for long-term pain after hernia surgery. Ann Surg 244(2):212–219 Schmedt C-G, Sauerland S, Bittner R. (2005) Comparison of endoscopic procedures vs Lichtenstein and other open mesh techniques for inguinal hernia repair. A meta-analysis of randomized controlled trials. Surg Endosc 19:188–199 Bittner R, Sauerland S, Schmedt C-G. (2005) Comparison of endoscopic techniques vs Shouldice and other open nonmesh techniques for inguinal hernia repair. A metaanalysis of randomized controlled trials. Surg Endosc 19:605–615 McCormack K, Scott NW, Go PM, Ross S, Grant AM and the EU Hernia Trialists Collaboration. (2003) Laparoscopic techniques versus open techniques for inguinal hernia repair. Cochrane Database Syst Rev (1)CD001785 Kehlet H, Bay-Nielsen M, Kingsnorth A. (2002) Chronic postherniorrhaphy pain–a call for uniform assessment. Hernia 6:178–181 Fränneby U, Gunnarsson U, Andersson U, Heuman R, Nordin P, Nyrén O, Sandblom G. (2008) Validation of an inguinal pain questionnaire for assessment of chronic pain after groin hernia repair. Br J Surg 95(4):488–493 Grant AM, Scott NW, O´Dwyer PJ, on behalf of the MRC Laparoscopic Groin Hernia Trial Group. (2004) Fiveyear follow-up of a randomized trial to assess pain and numbness after laparoscopic or open repair of groin hernia. Br J Surg 91:1570–1574 Liem MSL, Van Der Graaf Y, Van Steensel CJ, Boelhouwer RU, Clevers GJ, Meijer WS, Stassen LP, Vente JP, Weidema WF, Schrijvers AJ, van Vroonhoven TJ. (1997) Comparison of conventional anterior surgery and laparoscopic surgery for inguinal hernia repair. N Engl J Med 336:1541– 1547 Johansson B, Hallerbäck B, Glise H, Anesten B, Smedberg S, Román J. (1999) Laparoscopic mesh versus open preperitoneal mesh versus conventional technique for inguinal hernia repair: a randomized multicenter trial (SCUR Hernia Repair Study). Ann Surg 230(2):225–231 Neumayer L, Giobbe-Hurder A, Jonasson O, Fitzgibbons R Jr, Dunlop D et al. (2004) Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 350:1819– 1827

16. Berndsen F, Arvidsson D, Enander L-K, Leijonmarck CE, Wingren U, Rudberg C, Smedberg S, Wickbom G, Montgomery A. (2002) Postoperative convalescence after inguinal hernia surgery: prospective randomised multicenter study of laparoscopic versus Shouldice inguinal hernia repair in 1042 patients. Hernia 6:56–61 17. Arvidsson D, Berndsen FH, Larsson LG, Leijonmarck CE, Rimback G, Rudberg C, Smedberg S, Spangen L, Montgomery A. (2005) Randomized clinical trial comparing 5-year recurrence rate after laparoscopic versus Shouldice repair of primary inguinal hernia. Br J Surg 92:1085–1091 18. Berndsen F, Petersson U, Arvidsson D, Leijonmarck C, Rudberg C, Smedberg S, Montgomery A. (2007) Discomfort five years after laparoscopic and Shouldice inguinal hernia repair: a randomised trial with 867 patients. A report from the SMIL study group. Hernia 11(4):307–313 19. Ekelund A, Rudberg C, Smedberg S, Enander LK, Leijonmarck CE, Österberg J and Montgomery A. (2006) Shortterm results of a randomized clinical trial comparing Lichtenstein open repair with totally extraperitoneal laparoscopic inguinal hernia repair. Br J Surg 93:1060–1068 20. Eklund A, Montgomery A, Rasmussen I, Sandbue R, Bergkvist L, Rudberg C. (2009) Low recurrence rate after laparoscopic (TEP) and open (Lichtenstein) inguinal hernia repair. Ann Surg 249(1):33–38 21. Eklund A, Rudberg C, Leijonmarck CE, Rasmussen I, Spangen L, Wickbom G, Wingren U, Montgomery A. (2007) Recurrent inguinal hernia: randomized multicenter trial comparing laparoscopic and Lichtenstein repair. Surg Endosc 21:634–640 22. Taylor C, Layani L, Liew V, Ghusn M, Crampton N, White S. (2008) Laparoscopic inguinal hernia repair without mesh fixation: early results of a large randomised clinical trial. Surg Endosc 22(3):757–762 23. Olmi S, Scaini A, Erba L, Guaglio M, Groce E. (2007) Quantification of pain in laparoscopic transabdominal preperitoneal (TAPP) inguinal hernioplasty identifies marked differences between prosthesis fixation systems. Surgery 142(1): 40–46 24. Lovisetto F, Zonta S, Rota E, Mazzilli M, Bardone M, Bottero L, Faillace G, Longoni M. (2007) Use of human fibrin glue (Tissucol) versus staples for mesh fixation in laparoscopic transabdominal preperitoneal hernioplasty: a prospective, randomized study. Ann Surg 245(2):222–231 25. Lau H. (2005) Fibrin sealant versus mechanical stapling for mesh fixation during endoscopic extraperitoneal inguinal hernioplasty. A randomised prospective trial. Ann Surg 242:670–675 26. O’Dwyer PJ, Kingsnorth AN, Molloy RG, Small PK, Lammers B, Horeyseck G. (2005) Randomized clinical trial assessing impact of a lightweight or heavyweight mesh on chronic pain after inguinal hernia repair. Br J Surg 92:166–170 27. Junge K, Klinge U, Rosch R, Klosterhalfen B, Scumpelick V. (2002) Functional and morphologic properties of a modified mesh for inguinal hernia repair. World J Surg 26:1472–1480

34

Recurrence or Complication: The Lesser of Two Evils? A Review of Patient-Reported Outcomes from the VA Hernia Trial L. Neumayer

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Chapter 34 · Recurrence or Complication: The Lesser of Two Evils?

Introduction Inguinal hernia is one of the most common disease states affecting men worldwide. The direct and indirect costs of this condition, with or without repair, are great. Recent studies have questioned the need for repair in asymptomatic patients; however, in both of these studies, pain and discomfort were the main reasons for a crossover to repair from the »watchful waiting« group [1, 2]. Pain is now recognized as a common complication after hernia repair. In this review we intend to address, using previously reported data [3–5], the issue of whether a recurrence–which is viewed by most surgeons as a negative outcome–is worse for the patient in the long term than pain or other complications. Further, we review predictors of complications that may help guide surgeons in the choice of operation for individual patients.

Methods

34

The methods of the U.S. Department of Veteran Affairs (VA) hernia trial comparing laparoscopic versus open tension free hernia repair, as well as the analyses performed for evaluation of patientreported outcomes and predictors of complications, have been previously reported [3–6]. The study was designed to detect a 3% difference in recurrence at 3 years and to evaluate other surgeoncentered and patient-centered outcomes (complications/death, pain, functional status, activity levels, caregiver burden, and cost). In addition, we measured patient and surgeon satisfaction. As part of this large study, two new instruments, the Surgical Pain Scale (SPS) and the Activities Assessment Scale (AAS), were developed and validated [7, 8]. All results reported herein have been previously reported [3–6]. This report serves as an amalgamation of prior analyses. As a post hoc analysis, we also evaluated the relationship between patient-reported outcomes (PROs) and recurrence or complications [4]. In particular, we sought to determine the impact of recurrence and other complications on overall patient outcome as measured by the Medical Out-

comes Study Short Form 36 (SF-36). This analysis was limited to patients who had both preoperative and postoperative PRO assessment. Cumulative rates of recurrence and complications were used. Complications were further divided into four categories: (1) hematoma/seroma, (2) orchitis, (3) neuralgia of the leg or groin, and (4) other. Patientreported outcomes included the SF-36, the SPS, the AAS, and patient satisfaction. All of these outcomes were measured at baseline and at 2 weeks, 3 months, 6 months, and 1 and 2 years postoperatively. (Patient satisfaction, however, was not measured at 2 years.) To evaluate the relationships between preoperative and postoperative PROs, we used Pearson’s correlation coefficients. Univariate comparisons among groups were performed using analysis of variance for continuous variables and chi-square or Fisher’s exact test for categorical variables. Regression analyses were employed to determine significant predictors of postoperative PROs. As previously reported, we further analyzed predictors of short-term and long-term complications and long-term pain by initially looking for potential predictors with appropriate univariate statistics. Our initial analyses revealed different predictors for open and laparoscopic techniques, so we modeled these separately. Only outcomes with at least 50 occurrences and with p-values >0.2 in univariate comparisons were entered into regression models to ensure relative stability in the models [5].

Results As reported previously 2,134 men were randomized to Lichtenstein or laparoscopic (totally extraperitoneal or transabdominal preperitoneal) repair of their inguinal hernias [3]. Although a few patients did not undergo repair, 1,983 completed an operative intervention, and 1,696 were available for 2-year recurrence assessment. Nearly all of these patients (1,603) also had PRO data at 2 years (1,526 had PRO data at 1 year). Demographics of the patients with PRO data at 1 and 2 years were similar to those of the whole group (⊡ Table 34.1) [3, 4].

253 Chapter 34 · Recurrence or Complication: The Lesser of Two Evils?

34

⊡ Table 34.1. Demographic and outcome data, adapted from Hawn et al. [5] and Matthews et al. [6] (PRO patientreported outcome) Total study N=1,983

PRO subgroup at 2 years N=1,603

Open N (%)

Laparoscopic N (%)

Open N (%)

Laparoscopic N (%)

Recurrence

41/834 (4.9)

87/862 (10.1)

37 (4.6)

68 (8.5)

Neuralgia

99/950 (10.4)

71/943 (7.5)

67 (8.4)

53 (6.6)

Hematoma

17/950 (1.8)

50/943 (5.3)

14 (1.8)

41 (5.1)

Orchitis

7/950 (0.7)

11/943 (1.2)

6 (0.8)

11 (1.4)

Other

80/950 (8.4)

86/943 (9.1)

69 (8.6)

81 (10.1)

Patients with recurrence, a complication, or both reported scores for the AAS, SPS, and physical component portion of the SF-36 that were significantly different on univariate analyses (p<0.001) from those for patients without a recurrence or complication. Patient satisfaction also differed; 97% of patients who did not have a recurrence or complication were satisfied with their operation, whereas only 62% of those with a recurrence and 89% of those with a complication were satisfied. After adjustments were made for baseline preoperative scores and patient demographics, a recurrence did not affect the patient’s general health status as measured by the SF-36. However, patients with neuralgia or orchitis had significantly lower PCS scores than patients who did not suffer those complications. Patients with neuralgia had lower mental component scores than those without neuralgia. After open repair, patients with a recurrence had significantly more pain at rest and with activity than patients who had recurrence after laparoscopic repair. As would be expected, patients with self-reported neuralgia had higher pain scores on the SPS (10-mm difference at rest, 21-mm difference during work or exercise) compared with patients without neuralgia. Younger patients had more pain preoperatively and postoperatively than older patients did, but the magnitudes of reduction in pain scores were equivalent between younger and older patients.

Younger patients who were not actively employed prior to operation reported more limitations in activity during work or exercise as measured by the AAS. The presence of neuralgia, orchitis, or other complications also limited activity during work or exercise, but the presence of a recurrence did not limit activity during work or exercise. When operative techniques were compared, other complications after laparoscopic repair were accompanied by limitations in patient activity, whereas other complications after open repair did not seem to limit activity. Younger patients and those with a recurrence, neuralgia, or other complications were significantly less likely to be satisfied with the operation or their total hernia care when analyzed by logistic regression.

Predictors of Complications As previously reported, complications were divided into short term (occurring within 2 weeks of operation) and long term (occurring at 3 months and beyond) and occurred more frequently in patients who had undergone laparoscopic repair (39% vs. 33%, p=0.02) [3, 5]. The most common short-term complications in both the open and laparoscopic groups were wounds/scrotal hematomas/seromas and urinary retention. The most common long-term complications were seromas and chronic leg or groin pain. Wound

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Chapter 34 · Recurrence or Complication: The Lesser of Two Evils?

⊡ Table 34.2. Predictors of complications after open repair (multivariate analysis), adapted from Matthews et al. [6] (OR odds ratio; CI confidence interval; MCS mental component score) Complications (c-index of model)

Significant predictors

Adjusted OR (95% CI)

p-value

Short-term (0.655)

Type of hernia: recurrent

2.02 (1.22, 3.32)

0.006

Hispanic ethnicity

2.94 (1.03, 8.35)

0.043

Hernia into scrotum

2.31 (1.47, 3.94)

0.0005

SF-36 MCS score: OR for each 3-unit increase

0.95 (0.92, 0.99)

0.008

Age: OR for each 5-year increase

0.90 (0.84, 0.97)

0.003

Long-term (0.624)

⊡ Table 34.3. Predictors of complications after laparoscopic repair (multivariate analysis), adapted from Matthews et al. [6] (OR odds ratio; CI confidence interval; BMI body mass index) Complications (c-index of model)

Significant predictors

Adjusted OR (95% CI)

p-value

Short-term (0.644)

Enlargement of hernia in past 6 months

1.50 (1.10, 2.05)

0.01

Duration: present for >1 year

1.59 (1.16, 2.18)

0.004

Hernia into scrotum

2.02 (1.18, 3.46)

0.011

Prostatism

1.94 (1.34, 2.81)

0.0005

Type of hernia: recurrent

2.04 (1.27, 3.27)

0.003

Prostatism

1.71 (1.14, 2.57)

0.009

BMI: OR for each 1-unit BMI increase

1.07 (1.02, 1.12)

0.006

34 Long-term (0.631)

infection was infrequent at any time for both types of repair, and no patient required mesh removal. For both techniques, having a recurrent hernia repaired increased the likelihood of short-term complications, as did the presence of a hernia extending into the scrotum (⊡ Tables 34.2 and 34.3). Prostatism was a predictor for both short-term and

long-term complications in the laparoscopic group, while younger age was associated with long-term complications in the open group. Younger age was associated with a higher likelihood of long-term pain in both open and laparoscopic groups (the adjusted odds ratio for each 5-year increase in age was 0.82 in open repairs and 0.83 in laparoscopic repairs) [5].

255 Chapter 34 · Recurrence or Complication: The Lesser of Two Evils?

Discussion The VA hernia trial comparing laparoscopic and open tension-free inguinal hernia repair in men is one of the largest ever conducted. We planned to be able to examine both surgeon-centered (recurrence, complications, and death) and patient-centered (SF-36 functional status, surgical pain, activities) outcomes for the duration of the study, which included a minimum of 2 years of follow-up. Collecting such massive amounts of data has allowed analyses of many different outcomes. Our analysis of the relationship of patient-centered outcomes to recurrences and complications is one of the few based on prospectively collected data rather than recall data from patients mailed a survey years after their herniorrhaphy. From these further analyses, we have confirmed the findings of others that chronic pain is a significant and measurable adverse effect of hernia repair and that it is more common long term after open repairs and in younger patients. We have further elucidated that for most patients, chronic pain has a deleterious effect on overall functional status, whereas recurrence, although associated with pain, in and of itself does not negatively affect functional status as measured by the physical component score of the SF-36. In our cost-effectiveness analysis, we showed that laparoscopic repair was cost-effective for a unilateral hernia; it is possible that the finding of a decreased physical component score in patients with chronic pain and no recurrence is responsible for this finding [9]. In addition, we have identified some other predictors of complications, which will require further investigation as to whether they themselves are putative risk factors or surrogates for unmeasured factors. The strength of the VA hernia trial is that it was conducted in »real-life« practices, not in highly specialized hernia or laparoscopic centers, and therefore represents the current practice of most general surgeons. As part of the trial, data were collected prospectively, allowing analyses of many secondary outcomes. A limitation is that the study was performed within the Veterans Affairs healthcare system, in which the majority of pa-

34

tients needing inguinal hernia repair are not »good risk,« thus limiting to some extent the generalizability of our results.

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

Fitzgibbons RJ, Giobbie-Hurder A, Gibbs JO, Dunlop DD, Reda DJ, McCarthy M, Neumayer LA, et al. (2006) Watchful waiting vs repair of inguinal hernia in minimally symptomatic men: a randomized clinical trial. JAMA 295(3):285–292 O’Dwyer PJ, Norrie J, Alani A, et al. (2006) Observation or operation for patients with an asymptomatic inguinal hernia. A randomized clinical trial. Ann Surg 244(2): 167–173 Neumayer L, Jonasson O, Fitzgibbons R, Henderson W, Gibbs J, Carrico CJ, Itani K, Kim L, Pappas T, Reda D, Dunlop D, McCarthy, Hynes D, Giobbie-Hurder A, London MJ, Hatton-Ward S. (2003) Tension-free inguinal hernia repair: the design of a trial to compare open and laparoscopic surgical techniques. J Am Coll Surg 196(5):743–752 Neumayer L, Giobbie-Hurder A, Jonasson O, Fitzgibbons R, Dunlop D, Gibbs J, Reda D, Henderson W. (2004) Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 350(18):1819–1827 Hawn MT, Itani K, Giobbie-Hurder A, McCarthy M, Jonasson O, Neumayer LA. (2006) Patient reported outcomes following inguinal herniorrhaphy. Surgery 140:198–205 Matthews RM, Anthony T, Kim LT, Wang J, Fitzgibbons JR, Giobbie-Hurder A, Reda DJ, Itani KMF, Neumayer LA. (2007) Factors associated with postoperative complications and hernia recurrence for patients undergoing inguinal hernia repair: a report from the VA Cooperative Hernia Study Group Am J Surg 194(5):611–617 McCarthy M, Chang CH, Pickard AS, Giobbie-Hurder A, Price DD, Jonasson O, Gibbs J, Fitzgibbons R, Neumayer L. (2005) Visual analog scales for assessing surgical pain. J Am Coll Surg 201(2):245–252 McCarthy M, Jonasson O, Chang CH, Pickard AS, GiobbieHurder A., Gibbs J, Edelman P, Fitzgibbons R, Neumayer L. (2005) Assessment of patient functional status after surgery. J Am Coll Surg 201(2):171–178 Hynes D, Sroupe K, Luo P, Giobbie-Hurder A, Reda D, Kraft M, Itani K, Fitzgibbons R, Jonasson O, Neumayer L, for the Veterans Affairs Cooperative Studies Program 456 Investigators. (2006) Cost-effectiveness of laparoscopic versus open mesh hernia operation: results from a Department of Veterans Affairs randomized clinical trial. J Am Coll Surg 203(4):447–457

35

Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique G. G. Champault

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Chapter 35 · Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique

Introduction

35

The true incidence of chronic pain after inguinal herniorrhaphy is unknown, and until recently it was a secondary consideration, with the recurrence rate being deemed of greater importance. The incidence was reduced by the use of prostheses [1]. As recurrences have declined, though, more attention is now being focused on other measures of success, particularly quality of life. Numerous recent studies have examined the incidence of chronic pain after operations. Grant et al. [2] reported that 9.7% of their patients experienced chronic pain after surgery, and other studies [3–6] have put the figure as high as 34%. Typically, such complaints decrease over the course of the first year [7], but a significant number of patients do develop chronic and debilitating pain [8]. With the recognition that this is more common than was previously realized, numerous authors have begun to investigate the impact of pain on quality of life [9, 10]. Various factors have been examined to determine the etiology of postoperative pain. Patient age has been implicated, with the available data indicating that younger patients have a higher likelihood of postoperative pain [5, 10]. But a recent study [7] refuted this notion, finding that the incidence of chronic pain is evenly distributed among age groups. Preoperative pain seems to be a risk factor, with multiple studies [5, 6] showing that those who report pain beforehand are more likely to develop chronic pain afterward. Certain individuals can be physiologically or psychologically predisposed to develop chronic pain. Courtney et al. [8] found that patients with such symptoms after herniorrhaphy are more likely than most other people to suffer from other chronic pain conditions. Body habitus may play a role here because obese patients can have a higher incidence of postoperative inguinodynia [10]. Ferzli et al. [11] found that the probability of developing chronic pain was more than twofold higher in those undergoing ambulatory herniorrhaphy. The type of anesthetic administered has been examined as a possible factor in this problem. Nordin et al. [12] showed that local anesthesia was associated with less chronic pain than regional or general anesthesia.

Other risk factors for chronic pain include being employed and having private health insurance [5]. Direct injury to nerves, resulting in either partial or complete transection, can lead to neuroma formation and subsequent development of chronic pain. The ilioinguinal and iliohypogastric segments of the genital branch of the genitofemoral nerves are vulnerable to injury; when injured, they can produce pain syndromes that are refractory to narcotic and multidisciplinary management techniques. Some authors have also implicated the role of mesh [13, 14]. Demirer et al. [15] showed that when peripheral nerve tissue comes in contact with polypropylene mesh, myelin degeneration associated with edema and fibrosis occurs. However, multiple studies have examined this issue, and the weight of the evidence seems to indicate that mesh does not significantly increase the risk of chronic pain [8, 10, 16]. Operative technique may also play a role. No particular surgical approach has proved superior in terms of subsequent pain, although data suggest that the laparoscopic procedure [17] may be more beneficial. Douek et al. [18] found that after 5 years, the transabdominal preperitoneal procedure resulted in significantly less pain than an open tension-free mesh repair (2% vs. 10%). In contrast, the largest study [19] to date comparing open techniques with laparoscopy found no differences after 3 months. Multiple studies have examined the role of mesh. The etiological factors include irritation or damage of inguinal nerves by sutures or mesh [13], an inflammatory reaction against the mesh [20], or simply scar tissue. A recent systematic review of mesh techniques compared with nonmesh methods pointed out that no strong evidence indicated that the use of mesh increased the rate of chronic pain [1]. Recent studies [3] have pointed out that »mesh-induced pain« occurs more frequently than reported, including in tension-free techniques. Amid [21] identified »meshoma« as a radiologic entity and pathologic cause of chronic pain. Meshoma occurs when the mesh prosthesis becomes wadded into a ball because of nonfixation, insufficient fixation, or insufficient dissection to make adequate room for the prosthesis. In other situations, the weight of the evidence seems to indicate

259 Chapter 35 · Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis

that mesh does not significantly increase the risk of chronic pain [10, 16, 18]. But research into alternatives to polypropylene continues. Cobb et al. [22] have advocated the use of newer lightweight polypropylene, which may in theory result in less foreign body response and would improve operative outcomes. Post et al. [23] reported that after 6 months of follow-up, lightweight polypropylene mesh is preferable to conventional mesh for Lichtenstein repair of inguinal hernia. After this study, two randomized studies [24, 25] reported that use of a partially absorbable lightweight mesh was associated with less chronic pain than a nonabsorbable heavy mesh after 1 and 3 years. The frequency of recurrence was similar for the two meshes. A recent laparoscopic study indicated that fewer postoperative complications and an improved quality of life can be achieved by reducing the amount of polypropylene in meshes used for laparoscopic hernia repair [26]. Foreign body sensations were also fewer for lightweight meshes compared with conventional polypropylene mesh. In this study, Horstmann et al. [26] followed their patients only 1 year after surgery, when a foreign body sensation is more common than after 2 years. On the other hand, Paajanen [14] recently compared three different meshes [partially absorbable polypropylene–polyglactin mesh, lightweight polypropylene mesh (55 g/m2), and conventional densely woven polypropylene mesh] in a randomized trial of 228 patients (232 hernias) treated by Lichtenstein tension-free hernioplasty under local anesthesia in same-day surgery by the same surgeon using exactly the same surgical technique. He found no differences in pain or quality of life after 2 years of follow-up. The nature and quality of prostheses have evolved over the last 10 years, with polypropylene being the most common material. Many prostheses have offered additional refinements: anatomical molding; inclusion of elements to reduce the residual mass of nonresorbable material, thereby diminishing complications; and, recently, coatings of substances that assist in tissue acceptance and integration. We performed a study [27] to prospectively assess the results at 2-year follow-up in patients who underwent tension-free hernia repair by either the

35

Lichtenstein technique or laparoscopy, using two types of prostheses: polypropylene and beta-D-glucan-coated polypropylene (Glucamesh, Genzyme France). Glucan-coated prostheses are composed of an unwoven polypropylene mesh that is coated with beta–(1→3),(1→4)-D-glucan, a complex carbohydrate extract of oat. Oat beta-glucan is an entirely (100%) natural plant product that has been used in burn and wound care applications [28–30]. Beta-glucans have also been the subject of research regarding their roles as immunomodulators [31–34] and agents in wound healing [35, 36].

Patients and Methods Patients Between 2001 and 2003, 410 consecutive patients (396 men, 14 women) of mean age 54 years (range 18–84) underwent repair of inguinal hernias, 96 (23%) of which were bilateral and 56 (13%) recurrent. Most patients (95%) were classified as American Society of Anesthesiologists (ASA) physical status I or II [8], and 72 (17.5%) of them had a body mass index (BMI) above 30.

Methods All surgery was done under general anesthesia by four surgeons. Thrombosis prophylaxis and antibiotic prophylaxis were used in all cases. Lichtenstein repair was performed as first described [9]. The prosthesis was fixed at the inguinal ligament with five to seven stitches of polypropylene. In laparoscopic repair (totally extraperitoneal approach, or TEP), the Retzius space was developed and insufflated using three trocars. Prostheses were not fixed. This technique was preferred for bilateral hernias or for hernias that recurred after herniorrhaphy in young (20–45 years) active professionals or sportsmen or women with no anesthetic risk and a BMI under 30. All other patients underwent Lichtenstein repair. Two types of prosthesis were used: polypropylene of weight per unit area 105 g/m2 (Bard, Ethicon) and polypropylene of weight per unit area

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Chapter 35 · Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique

50 g/m2 coated with beta-D-glucan (Glucamesh; Genzyme France), a plant derivative (oat) that promotes healing and has an immunomodulatory effect. Patients were randomly assigned to the two groups depending on whether they agreed to be included in a prospective study [10]. All patients were followed up prospectively for at least 2 years by a surgeon not involved in the study. Recurrence was confirmed by physical examination or repeat surgery. Chronic pain was assessed using a visual analog scale (VAS) and a validated questionnaire [11]. Pain was considered mild for a VAS score below 3, moderate below 5, and severe or debilitating above 5.

Statistics Quantitative values are given as means ± standard deviation. The Kruskal–Wallis test or Wilcoxon test was used for (nonparametric) comparison of the two groups. For qualitative parameters, percentages were compared using the chi-square test. Differences were considered statistically significant for p-values <0.05. The statistical analyses were done using SPSS 10.0 software for Windows.

Results

35

Lichtenstein repair was done in 273 (66.5%) patients, with polypropylene mesh in 215 (78.7%) and Glucamesh in 58 (21.3%). Laparoscopic repair was used in 137 patients, with polypropylene mesh in 80 (58.4%) and Glucamesh in 57 (41.6%). In

each of these two groups, the populations were comparable in terms of age, gender, type of hernia, ASA score, and incidence of obesity. The mean duration of hospitalization was 2.82 days (range 1–5), independent of the technique or mesh. Two-year follow-up was possible in 85.1% of patients (n=349: 117 TEP, 232 Lichtenstein) and was comparable for the two techniques used. At 2 years, recurrence had occurred in 10 cases (2.8%) and was independent of the technique [TEP n=2/117 (1.7%) vs. Lichtenstein n=8/232 (3.4%), not significant] or of the type of mesh [Glucamesh n=2/104 (1.9%) vs. polypropylene n=8/245 (2.4%), not significant]. (⊡ Table 35.1). At 2 years of follow-up, 69 patients presented with residual mild (VAS<3) or moderate (VAS<5; 19.7%) pain and 11 with intense pain (VAS>5; 3.1%). Moderate pain (⊡ Tables 35.2 and 35.3) was significantly less frequent (p=0.05) with Glucamesh than with polypropylene mesh (4.8% vs. 26.1%) irrespective of the repair technique (6.5% vs. 27.2% for laparoscopy; 3.7% vs. 25.6% for Lichtenstein). There was no significant difference between the two techniques in the Glucamesh group (6.5% vs. 3.7%) or the polypropylene mesh group (27.2% vs. 25.6%). This was also true for chronic, severe, debilitating pain (⊡ Tables 35.4 and 35.5). Pain characteristics were comparable whatever the repair technique (⊡ Table 35.6).

Discussion There is no consensus concerning the repair technique for inguinal hernia. However, it is clear that the use of prosthetic strengthening significantly

⊡ Table 35.1. Two-year recurrence (n%) as a function of technique and mesh (ns not significant) n

Recurrence

%

p

Lichtenstein

232

8

3.4

ns

Laparoscopy

117

2

1.7

ns

Glucamesh

104

2

1.9

ns

Polypropylene

245

8

2.4

ns

Total

349

10

28

35

261 Chapter 35 · Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis

repair, which is now the most widespread technique because of its advantages in terms of cost, risk, and simplicity. Nonetheless, the indications for laparoscopic repair are still subject to debate.

reduces the incidence of recurrence [37]. Tensionfree techniques may reduce the incidence of residual pain [9, 10]. This explains the preference for the laparoscopic approach and for Lichtenstein

⊡ Table 35.2. Incidence of chronic pain (n%) as a function of technique (ns not significant) Laparoscopy

Lichtenstein

Total

p

Glucamesh

3/51 (6.5%)

2/53 (3.7%)

5/104 (4.8%)

ns

Polypropylene

18/66 (27.2%)

46/179 (25.6%)

64/245 (26.5%)

ns

Total

21/117 (17.9%)

48/232 (20.6%)

69/349 (19.7%)

ns

⊡ Table 35.3. Incidence of chronic pain (n%) as a function of mesh Glucamesh

Polypropylene

p

Totally extraperitoneal approach

3/51 (6.5%)

18/66 (27.2%)

p=0.02

Lichtenstein

2/53 (3.7%)

46/179 (25.6%)

p=0.02

Total

5/104 (4.8%)

64/245 (26.5%)

p=0.02

⊡ Table 35.4. Incidence of severe pain (visual analog score >5) as a function of technique (ns not significant) Laparoscopy

Lichtenstein

Total

p

Glucamesh

1/51 (1.9%)

0/53 (0%)

1/104 (0.9%)

ns

Polypropylene

3/66 (4.5%)

7/179 (3.3%)

10/245 (4%)

ns

Total

4/117 (3.4%)

7/232 (3%)

11/349 (3.1%)

ns

⊡ Table 35.5. Incidence of severe pain (visual analog score >5) as a function of mesh Glucamesh

Polypropylene

p

Totally extraperitoneal approach

1/51 (1.9%)

3/66 (4.5%)

p=0.27

Lichtenstein

0/53 (0%)

7/179 (3.3%)

p=0.02

Total

1/104 (0.9%)

10/245 (4%)

p=0.02

Glucamesh

Polypropylene

p

Groin

67%

77%

ns

Testicle

50%

34%

ns

⊡ Table 35.6. Location of pain (ns not significant)

262

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Chapter 35 · Chronic Pain After Inguinal Hernia Repair: The Choice of Prosthesis Outweighs That of Technique

We used laparoscopy in young, nonobese patients with bilateral or recurrent hernia who were active professionally or in sports and who had no anesthetic risk. We applied the same indications to the laparoscopic and Lichtenstein groups, which were therefore perfectly comparable. The reported 2-year recurrence rate is comparable for Lichtenstein repair and laparoscopic repair (2–5%) [38, 39], which accords with our experience (2.8%) in which this incidence was independent of the technique or the prosthetic mesh. The choice of prosthesis is even less well defined and subject to criteria that are often costrelated and subjective or personal. The characteristics of the ideal prosthesis are well defined: large mesh, solid, flexible, low specific weight, ability to become incorporated in tissues, and biologically inert. Most meshes are made of polypropylene or polyester. Using these principles, a great variety of products have been developed and adapted to techniques or practices (laparoscopy): composite, two-faced meshes that are coated to promote healing and facilitate tissue integration. Coating with animal collagen has proved effective but carries a small biological risk (cattle) or is subject to religious restrictions (pig). Beta-Dglucan is an entirely natural plant product that promotes healing and has an immunomodulatory effect [29, 31, 33, 34]. Beta-D-glucan-coated meshes are effective in terms of recurrence, quality of life, and chronic pain [40, 41]. In the present study, we have shown that the 2-year recurrence rate was the same regardless of technique, mesh, or the mesh’s weight per unit area. Studies of lightweight meshes have yielded contrasting results [24, 42]. When they compared outcomes after laparoscopic TEP inguinal repair using new lightweight (28 g/m2) and traditional (85 g/m2) heavyweight mesh, Khan et al. [43] found less discomfort and pain in the lightweight group at 3-month follow-up. Severity of numbness was less with lightweight mesh, suggesting less nerve interference and less inflammatory response. Also, the use of lightweight mesh for Lichtenstein hernia repair did not affect the recurrence rate, but some aspects of pain and discomfort were improved 3 years after surgery [24].

Chronic pain after hernia repair has been studied extensively [3, 6, 17, 43] but is difficult to assess. Specific validated questionnaires [42, 44] have been developed to evaluate and compare quality of life as a function of technique. Numerous factors have been implicated: anatomical factors (nerves), type of hernia, technique, surgical field, and also the mesh and its fixation. In our practice, the meshes used in TEP are not fixed, and those used in Lichtenstein repair are fixed with a few sutures on the inguinal ligament. At 2-year follow-up, these techniques were identical in comparable groups of patients, whatever the type of prosthesis used. There was no difference in chronic pain, or even in pain qualified as severe, between TEP and Lichtenstein repair. There was, however, a significant difference in favor of Glucamesh compared with polypropylene mesh in the groups compared, irrespective of the repair technique. These advantages may stem from the low weight per unit area of Glucamesh but above all from the quality of the beta-D-glucan coating.

Conclusion Our findings suggest that at 2-year follow-up, the quality of hernia repair in terms of efficacy and quality of life is determined more by the characteristics of the prosthesis than by the technique used.

References 1. EU Hernia Trialist Collaboration (2000). Mesh compared with non mesh methods on open groin hernia repair. Systematic review of randomized controlled trial. Br J Surg 87, 854–859 2. Grant AM, Scott NW, O’Dwyer PJ (2004). Five-year follow-up of a randomized trial to assess pain and numbness after laparoscopic or open groin hernia. Br J Surg 91, 1570– 1574 3. Bay Nielsen M, Perkins FM, Kehlet H (2001). Danish Hernia Database. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 233, 1–7 4. Nienhuijs SW, Boelens OB, Strobbe LJ (2005). Pain after anterior mesh hernia repair. J Am Coll Surg 200, 885–889 5. Franneby U, Sandbloom G, Nordin P, Gunnarson U (2006). Risk factors for long term pain after hernia surgery. Ann Surg 244, 212–219

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6. Callesen T, Beck K, Kehlet H (1999). Prospective study of chronic pain after groin hernia. Br J Surg 86, 1528–1531 7. Aasvang EK, Bay Nielsen M, Kehlet H (2006). Pain and functional impairment 6 years after inguinal herniorrhaphy. Hernia 10, 316–321 8. Courtney CA, Duffy K, Serpell MG (2002). Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 89, 1310–1314 9. Silen W (2002). Chronic pain and quality of life following open inguinal hernia repair. Br J Surg 89, 123 10. Poobalan AS, Bruce J, King PM, Chambers WA, Krukowski ZH, Smith WCS (2001). Chronic pain and quality of life following open inguinal hernia. Br J Surg 88, 1122–1126 11. Ferzli G, Edwards E, Khoury G (2007). Chronic pain after inguinal herniorrhaphy. J Am Col Surg 205, 1, 333–341 12. Nordin P, Zetterstrom H, Guynnarson U, Nilsson E (2004). Choice of anesthesia and risk of reoperation for recurrence in groin hernia repair. Ann Surg 204, 187–192 13. Heise CP, Starling JR (1998). Mesh inguinodynia: a new clinical syndrome after inguinal herniorrhaphy. J Am Coll Surg 187, 514–518 14. Paajanen H (2007). A single surgeon randomized trial comparing three composite meshes on chronic pain after Lichtenstein hernia repair in local anesthesia. Hernia 11, 335–339 15. Demirer S, Kepenecki, Evirgen O (2006). The effect of polypropylene mesh on ilioinguinal nerve in open mesh repair of groin hernia. J Surg Res 131, 175–181 16. Koninger J, Redecke J, Butters M (2004). Chronic pain after hernia repair: a randomized trial comparing Shouldice, Lichtenstein and TAPP. Langenbecks Arch Surg 389, 361–365 17. Kumar S, Wilson RG, Nixon SJ, MacIntire IMC (2002). Chronic pain after laparoscopic and open mesh repair of groin hernia. Br J Surg 89, 1476–1479 18. Douek M, Smith G, Oshavo A (2003). Prospective randomized controlled trial of laparoscopic versus open hernia mesh repair: five years follow up. Br J Med 326, 1012– 1013 19. Neumayer L, Giobbie-Hinder A, Jonasson O (2004). Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 350, 1819–1827 20. Di Vita G, Milano S, Frazzetta M (2000). Tension free hernia repair is associated with an increase of inflammatory response markers against the mesh. Am J Surg 180, 203– 207 21. Amid PK (2004). Radiological images of meshoma: a new phenomenon after prosthetic repair of the abdominal wall hernia. Arch Surg 139, 1297–1298 22. Cobb WS, Kercher KW, Heniford BT (2005). The argument for lightweight polypropylene mesh in hernia repair. Surg Innov 12, 63–69 23. Post S, Weiss B, Willer M, Neufang T, Lorenz D (2004). Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair. Br J Surg 91, 44–48 24. Bringman S, Wollert S, Osterberg J, Smedberg S, Granlund H, Heikkinen T (2006). Three years results of a randomized

25.

26.

27.

28.

29.

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31.

32.

33.

34.

35. 36.

37.

38.

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clinical trial of lightweight or standard polypropylene mesh in Lichtenstein repair of primary inguinal hernia. Br J Surg 96, 1056–1059 O’Dwyer PJ, Kingsnorth AN, Molloy RG, Small PK, Lammers B, Horeyseck G (2005). Randomized clinical trial assessing impact of a lightweight or heavy weight mesh on chronic pain after inguinal hernia repair. Br J Surg 92, 166–170 Horstmann R, Hellwig M, Classen C, Rottgermann S, Palines D (2006). Impact of polypropylene amount on functional outcome and quality of life after inguinal hernia repair by the TAPP procedure using pure, mixed and titanium-coated meshes. World J Surg 30, 1742–1749 Champault G, Bernard C, Rizk N, Polliand C (2007). Inguinal hernia repair: the choice of prosthesis outweighs that of the technique. Hernia 11, 125–128 Delatte SJ, Evans J, Hebra A, Adamson W, Othersen HB and Tagge EP (2001). Effectiveness of beta-glucan collagen (BGC) for treatment of partial thickness burns in children. J Ped Surg 36, 113–118 Lozano DD, Noordenbos J, Hansbrough JF (2002) The use of glucan II in the treatment of donor sites. J Burn Care Rehab 23, S81 Richards T, Azad S, Dziewulski P, Moiemen N, Dziewulski P (2000). Randomized controlled trial of dressings for partial thickness facial burns. J Burn Care Rehab 21, part 2, S219 Abel G, Czop JK (1992). Stimulation of human monocyte beta-glucan receptors by glucan particles induces production of TNF alpha and IL 1Beta. Int J Immunopharmacol 14, 1363–1373 Browder W, David W, Lucore P, Petrus H, Jones E, McNamer R (1988). Effect of enhanced macrophage function on early wound healing. Surgery 104, 224–230 de Fellippe jr J, da Rocha e Silva Jr M, Maciel FM, Soares A, Mendes NF (1993). Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). Surg Gynecol Obstet 177, 383–388 Estrada A, Yun CH, Van Kessel A, Li B, Hunta S (1997). Immunomodulatory activities of oat beta-Glucan in vitro and in vivo. Microbiol Immunol 41, 991–998 Di Pietro LA (1995). Wound healing: the role of the macrophage and others immune cells. Shock 4, 233–240 Wolk M, Danon D (1985). Promotion of wound healing by yeast glucan evaluated on single animals. Med Biol 63, 273–280 Wrigland WW, Van Den Tol MP, Luijendijih RW, Hop WCP, Busschbacht JJV, de Lange DCD, Van Geldere D, Rottier AB, Vegt PA, Ijzermans JNM and Jeekel J (2002). Randomized trial of non mesh versus mesh repair of primary inguinal hernia. Br J Surg 89, 293–297 Arvidson D, Berndsen FM, Larsson LG. Leijonmarck CE, Rimback G, Rudberg C, Smedberg S, Spangen L, Montgomery A (2005). Randomized clinical trial comparing 5 years recurrence rate after laparoscopic versus Shouldice repair of primary inguinal hernia. Br J Surg 92, 1085–1091

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39. Wara P, Bay Nielsen M, Jul P, Bendix J, Kehlet H (2005). Prospective nationwide analysis of laparoscopic versus Lichtenstein repair of inguinal hernia. Br J Surg 92, 1277– 1281 40. Barrat C, Seriser F, Arnoud R, Trouette P, Champault G (2004). Inguinal hernia repair with beta glucan coated mesh: prospective multicenter study (115 cases). Preliminary results. Hernia 8, 33–38 41. Champault G, Barrat C (2005) Inguinal hernia repair with beta glucan coated mesh: results at two years follow up. Hernia 9, 125–130 42. Conze J, Kingsnorth AN, Flament JB, Simmermacker P, Arlt G, Langer C, Shippers E, Hartley A, Schlumpelick V (2005). Randomized clinical trial comparing lightweight composite mesh with polyester or polypropylene mesh for incisional hernia repair. Br J Surg 92, 1488–1493 43. Khan LR, Kumar S, Nixon SJ (2006). Early results for new lightweight mesh in laparoscopic totally extraperitoneal inguinal hernia repair. Hernia 10, 303–308

Discussion Schumpelick: Thank you very much for this pre-

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sentation, I think these are excellent results. How do you explain your results? How is glucan working? Champault: I think there are three explanations: First, it’s a lightweight mesh. Second, there is no fixation, because of adhesiveness. Especially in TEP hernia repair we do not fix the mesh anymore. Schumpelick: Is glucan like a glue? Champault: There is no glue on this mesh. But when you use this mesh in TEP hernia repair and you put the mesh directly on the muscle, you don’t need any fixation or tacks. And when you perform a Lichtenstein hernia repair, you only have to put in the prosthesis. In this study we used the official technique described by Amid with a running suture on the inguinal ligament. And third, with regard to the role of glucan, I have seen the use of glucan in burned patients. There it is very efficient, and you win many days in healing. Perhaps there is an action in the integration of the prosthesis in the muscle and possibly, as the experimental studies have shown, an action of the inflammatory reactions. Schumpelick: And then you mentioned in your discussion the covering of meshes with collagen. Is that not working anymore? Champault: There is a problem with collagen because you use the same product of collagen to fa-

cilitate the integration in the muscle and secondly to avoid an adherence. And that is a paradox. In the literature there is no A-level publication showing the usefulness of collagens. And the company (Covidien) have put the same prosthesis without collagen on the market – to be in the prize only! Post: You cannot differentiate the difference between the effect of lightweight and heavyweight and the glucan. So it might be hypothesized that the only difference is due to the light weight and not to glucan. In your randomized trial you started just now, do you compare the same lightweight with and without glucan? Champault: It probably will be the next trial. Smeds: Very interesting results. In order to understand the mechanisms more, I am just curious to know whether you allocated the surgeons to the different type of meshes. Did you have the polypropylene surgeons and the glucan surgeons? Because we know that there is a significant difference if you are a high-volume surgeon or a low-volume surgeon. Champault: No, the same surgeons. In a previous study we have shown that the results of trainees are the same as the results of consultants or more experienced surgeons. In this study, the repairs were performed within the whole group of our surgeons.

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The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia S. D. Demirer, I. Kepenekci, O. Evirgen, O. Birsen, A. Tuzuner, S. Karahuseyinoglu, M. Ozban, E. Kuterdem

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Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia

Introduction

Material and Methods

Open or laparoscopic mesh repair of groin hernia is one of the most common elective operations performed by general surgeons. Because of low recurrence rates, the concept of tension-free mesh repair methods has gained wide acceptance. The development of chronic pain after inguinal hernia repair is a well-known long-term complication, with the reported frequency of pain varying from 0% to 37% [1–11]. Some studies have reported a lower incidence of pain, 2–2.5%, after laparoscopic hernia repair than after open mesh repair [3, 4, 8, 11–15]. The complaint of chronic pain following inguinal hernia repair can continue for months or even years. Several risk factors associated with this have been identified, including recurrent hernia repair, the patient’s insurance status, day surgery, patient age less than 60 years, intensity of early postoperative pain, experience of the surgeon, and type of surgical procedure used [3, 6, 9, 16]. Mesh inguinodynia was described as »a new clinical syndrome« after inguinal herniorrhaphy. The development of this chronic debilitating pain after herniorrhaphy has been attributed to several mechanisms, including injury or entrapment of the sensory nerves (ilioinguinal, iliohypogastric, genitofemoral, or lateral femoral cutaneous nerves) and mesh inguinodynia [2, 3, 6–8, 17]. Partial or complete division, neuroma formation, stretching, contusion, crushing, electrical damage, or suture compression can injure sensory nerves in close proximity to the operative field and cause neuralgia. Secondary damage to a sensory nerve may also result from scar tissue compression or from irritation by an adjacent inflammatory process such as a suture granuloma or mesh. Polypropylene synthetic mesh causes inflammatory reaction and formation of scar tissue [2, 6, 8, 11, 17, 18]. The ilioinguinal nerve is a sensory nerve that is usually preserved during hernia repair, but it can interfere with placement of the mesh and may be traumatized inadvertently during operation. In this experimental study, we aimed to evaluate damage or entrapment of the ilioinguinal nerve caused by polypropylene synthetic mesh after groin hernia repair.

Our study protocol was reviewed and approved by the ethics committee of Ankara University School of Medicine. All animals received humane care in accordance with the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the U.S. National Institutes of Health (NIH publication No. 85–23, revised 1985).

Experimental Design Twenty-four New Zealand rabbits weighing 2.4– 2.7 kg were included in our study. They were subjected to 1 week of preliminary conditioning during which time they received standard chow and water ad lib. They were housed in a temperatureand humidity-controlled environment, two per cage, with a 12-h light–dark cycle. Preoperative antibiotics (cefazolin 10 mg/kg) were administered intramuscularly 30 min prior to skin incision. The rabbits were anesthetized by an intramuscular injection of ketamine hydrochloride (35 mg/kg) and Xylocaine (5 mg/kg). The animals were placed in a dorsal recumbent position, followed by hair removal from the inguinal area. The inguinal and scrotal regions were shaved and prepared with Betadine solution. In all animals, the inguinal areas were explored bilaterally through an inguinal incision. The ilioinguinal nerve was identified on both sides and synthetic polypropylene mesh placed on only one side (⊡ Fig. 36.1). The ilioinguinal nerve was in touch with polypropylene mesh on this side (⊡ Fig. 36.2). We designated the right groin as the control and the left groin as the experimental side in each animal. After the operation, the inguinal incisions were closed in anatomical layers with 3-0 monofilament suture. All rabbits tolerated the surgery well, and they were followed until reexploration. Three months after surgery, the animals were anesthetized using intramuscular ketamine hydrochloride, and bilateral inguinal exploration was performed again, with samples of nerve tissue taken from both sides. The samples of nerve tissue were divided into two groups as control and experimental groups. An internation-

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and examined under a light microscope (Zeiss Axio Scope photomicroscope). After double staining with uranyl acetate and lead citrate, ultrathin sections were examined and photographed using a LEO 906E transmission electron microscope. For light microscopic study, inguinal peripheral nerve tissues were fixed in 10% formaldehyde. Samples were dehydrated by immersion in a series of alcohol concentrations and embedded in paraffin; 5-μm sections were stained with hematoxylin and eosin (H&E) and Masson’s trichrome and examined under a light microscope. ⊡ Fig. 36.1. Ilioinguinal nerve of the rabbit after dissection

Morphometric Analysis

⊡ Fig. 36.2. Polypropylene mesh was laid in close proximity to the ilioinguinal nerve

For morphometric analysis, photographic color images from semithin sections of experimental and control groups were obtained with the Zeiss Axio Scope photomicroscope at ×250 magnification. The measurements were obtained using Adobe Photoshop 7.0 software. The graphic file format of the images is JPEG, and resolution was set at 500 pixels per inch. Myelinated fiber diameter, axon diameter, G-ratio (axon diameter/myelinated fiber diameter), myelin thickness, and the numbers of nerve fibers with diameters of ≤4 μm, 5–8 μm, and ≥9 μm were assessed in a blinded fashion using a semiautomated procedure [20].

Statistics ally accepted standard definition of pain persisting beyond the normal tissue healing time, assumed to be 3 months, was used in our study [19].

Histological Tissue Processing For electron microscopic study, inguinal peripheral nerve specimens from the control and experimental groups were fixed in 2.5% glutaraldehyde in 0.1 M phosphate buffer and postfixed in 1% osmium tetroxide. Tissue samples were dehydrated through a graded series of ethanol and propylene oxide embedded in araldite. Semithin sections were stained with toluidine blue-Azure II

Statistical analysis was performed using the adjusted Student‘s t-test for clustered data and the adjusted chi-square test for clustered binary data, comparing the mesh-laid side of each group to the control side of the same group. A p-value <0.05 denoted a statistically significant difference.

Results No intraoperative or postoperative deaths occurred in the rabbits, and we observed no infective complications in either the control or the experimental sides during 3 months of follow-up. There was

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Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia

a statistically significant difference between the mean operating times in the two groups (13 min in the control group vs. 24 min in the experimental group, p<0.05). During reexploration, we found macroscopically dense fibrotic tissues encompassing the polypropylene mesh and adhesions on the study side 3 months after surgery. On the experimental side, the floor of the inguinal region was very tight, and dissection as well as removal of the ilioinguinal nerve was difficult because of fibrotic changes. The nerve had thickened and adhered to the mesh and adjacent inguinal region. There was minimal fibrosis on the control side; therefore, the ilioinguinal nerve was divided and removed easily on this side.

a

Histological and Morphometric Assessment

36

H&E-stained sections from the experimental group after 3 months revealed inflammatory reaction and increased connective tissue that formed areas of fibrosis around polypropylene mesh islands (⊡ Fig. 36.3a, b). Light microscopic examination of H&E-stained and Masson’s trichrome-stained sections of peripheral nerves from the control group were normal in appearance (⊡ Fig. 36.4a, b), but the nerve fascicles in the experimental group operated with mesh showed axonal dilatation and mild to severe loss of myelinated axons (⊡ Fig. 36.5a, b). Examination of semithin sections of peripheral nerve fascicles from the control group showed almost intact myelinated and unmyelinated fibers (⊡ Fig. 36.5c). The endoneurium of closely located myelinated fibers appeared to be normal. Most of the myelin sheath layers and the thickness of equal-size fibers were the same and showed normal morphology. Electron microscopic examination of semithin and ultrathin sections of nerve morphology in the experimental group operated with mesh exhibited endoneurial edema with thickening of both the endoneurium and perineurium, causing separation of nerve fibers (⊡ Fig. 36.5d, d insert). A few extra layers of connective tissue formation in some nerve fibers of the experimental group suggested early onion-bulb formations. Myelin sheaths of fi-

b ⊡ Fig. 36.3. Experimental group at the 3rd postoperative month: interface of the mesh and recipient tissue (pmg polypropylene mesh graft). Double asterisks (**) indicate connective tissue around polypropylene mesh islands (patches) forming fibrosis and inflammatory reaction. Arrowheads show striated muscle. a Original magnification ×100. b Original magnification ×200. Hematoxylin–eosin staining

bers in the experimental group showed undulation toward the axoplasm and the endoneurium. In the experimental group we also observed separation of myelin layers from each other as a prominent feature of myelin degeneration in nerve fibers. Axoplasms also exhibited edema and crystallization (⊡ Fig. 36.6a–d).

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Results of the morphometric assessment are outlined in ⊡ Table 36.1. Fiber diameter and axonal diameter were increased in the experimental group compared with the controls as a result of axonal dilatation, and this difference was statistically significant. The G-ratio, which is considered normal in the range of 0.60–0.64, increased in the experimental group compared with controls as a result of myelin sheath thinning; the difference was statistically significant. Myelin thickness was decreased moderately on the mesh side compared with the control side, but there was no statistically significant difference between them. The number of nerve fibers considered healthy, with a diameter <9 μm, was higher in the control group than in the experimental group (Pcontrol=0.783 vs. Pmesh=0.570), and the difference was statistically significant (p<0.001) with an adjusted chi-square test for clustered binary data.

a

Discussion

b ⊡ Fig. 36.4. Light microscopic images of peripheral nerves of control group. a Arrowhead axon; arrow Schwann cell nucleus; E endoneurium; P perineurium; Ep epineurium. Original magnification ×400. Masson’s trichrome staining. b Arrowheads axons; arrow Schwann cell nucleus. Original magnification ×400. Hematoxylin–eosin staining

It is usual to preserve the ilioinguinal nerve, but it can interfere with placement of the mesh and may be traumatized inadvertently during operation. The increased surface area of the mesh might allow adherence of nerves or abrasion and account for an increased risk of neuropathic pain. Using prosthetic mesh for inguinal hernia repair is well accepted. But despite favorable clinical outcomes, patients who undergo mesh hernia repair may complain of severe, debilitating pain and pose a bothersome chronic management problem [1, 21, 22]. Local analgesic or steroid injections, various pharmaceuticals, behavioral therapy, cryotherapy, alcohol or phenol injections, neurectomy, and mesh removal are frequently used in treatment [2, 18]. Delayed presentations of mesh inguino-

⊡ Table 36.1. Peripheral nerve morphometry Average fiber diameter, mean ± SD

Average axon diameter, mean ± SD

Average G-ratio, mean ± SD

Myelin thickness, mean ± SD

Mesh side

9.05±0.24a

6.17±0.11a

0.68±0.007a

1.98±0.11

Control side

6.91±0.14

4.17±0.09

0.59±0.004

2.73±0.06

ap<0.001

significant with adjusted Student’s t-test for clustered data

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Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia

dynia may occur, possibly secondary to chronic scarring or neuroma formation. The mesh as a foreign body induces a dense fibroblastic response, creating scar tissue and imparting strength to the floor. Despite wide acceptance of this technique, there is little data regarding the effects of the mesh

a

bioprosthesis and its resulting fibrotic reaction on adjacent structures such as the spermatic cord or peripheral nerves in the inguinal region [23–28]. In our study we aimed to evaluate the local effects of mesh on the ilioinguinal nerve. Histopathological and morphometric changes of the

b

36 c

⊡ Fig. 36.5. a,b Light microscopic images of experimental group. a Asterisks axonal loss; P perineurium; Ep epineurium; arrowhead Schwann cell nucleus; arrows axons. Original magnification ×400. Hematoxylin–eosin staining. b Asterisks axonal loss; arrow axon; arrowhead Schwann cell nucleus; P perineurium; Ep epineurium; E endoneurium. Original magnification ×400. Masson’s trichrome staining. c, d, d insert Semithin

d

sections of peripheral nerves. c Arrow myelin sheath; asterisks unmyelinated nerves; P perineurium. Original magnification ×1,000. Toluidine blue staining. d, d insert Arrowheads extra collagen fiber layers (onion-bulb formation); asterisks separation of myelin sheath; arrows undulation of myelin sheath; P perineurium; Ep epineurium; double asterisks Schwann cell nucleus. Original magnification ×1,000. Toluidine blue staining

271 Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve

ilioinguinal nerve in the mesh group (mentioned in the results section of this paper), such as axonal dilatation, loss of myelinated axons, endoneurial edema, separation of myelin layers, increased fiber and axon diameters, and increased G-ratio, may be implicated in the etiology of chronic pain fol-

lowing inguinal hernia repair. But it is difficult to make a definitive statement regarding the impact of these histopathological changes on chronic pain because animal models, not human beings, were used in this experimental study. It is very well known that pain is a subjective complaint;

a

b

c

d

⊡ Fig. 36.6. Transmission electron microscopic (TEM) images of experimental group. a Axp axonal dilatations and axoplasm; double asterisks myelin sheath separation; umyn unmyelinated nerves; SCCy Schwann cell cytoplasm. TEM ×3,597. b Double asterisks extra collagen fibers around endoneurium suggesting onion-bulb formation; arrows myelin sheath degeneration and separation; asterisks myelin undulation; ms myelin

36

sheath. TEM ×2,784. c c collagen fibers; double asterisks endoneurial edema; umyn unmyelinated nerves; SCCy Schwann cell cytoplasm; myelin sheath. TEM ×4,646. d Axp crystallization of nerve fibers in axoplasm; double asterisks endoneurial edema; L lipid droplets; asterisks inclusion body in Schwann cell cytoplasm; SCCy Schwann cell cytoplasm; arrowhead degenerative inclusions between myelin layers. TEM ×12,930

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Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve in Open Mesh Repair of Groin Hernia

certainly, scaling and establishment of correlation with these histopathological changes cannot be done in animal models. Polypropylene mesh serves as a flexible lattice supporting the ingrowth of connective tissues from the base of the wound and is known to incite a prompt fibroblastic response, imparting strength to the repair. An extensive inflammatory and fibroblastic granulomatous reaction occurs in response to the foreign material, which causes dense adhesions when the material is placed adjacent to visceral organs [29, 30]. According to our macroscopic and microscopic findings, the ilioinguinal nerve was affected by the resultant fibrotic reaction to the mesh (⊡ Fig. 36.3a, b). Peripheral neuropathy following mesh herniorrhaphy was most likely due to incorporation of adjacent nerve fibers in the fibroblastic reaction incited by mesh. During the reexploration, we performed extensive dissection to find and ensure adequate mobilization for the ilioinguinal nerve because of the fibrotic changes in the experimental group. It has been argued that several factors may contribute to the development of chronic groin pain; one of these factors may be nerve entrapment. The nerves may hinder the dissection or may lie across the prosthetic mesh on the posterior inguinal wall. Chronic groin pain after hernia repair can possibly be caused by the entrapment of peripheral nerves in the scar tissue formed by the mesh [2–4, 6–8, 17]. Uzzo et al. [27] demonstrated that entrapment of the ilioinguinal nerve or its branches by the mesh reaction gave rise to a traumatic neuroma. In our study, the light microscopic and ultrastructural changes seen in peripheral nerves in the experimental group operated with mesh suggest that mechanical compression of peripheral nerves is associated with myelin degeneration, endoneurial and perineurial edema, thickening of collagen layers around axons (called onion-bulb formation), and axonal loss that may cause chronic inflammatory demyelinating peripheral neuropathy. We think that inflammatory and fibrotic reactions occurring in response to the foreign material may have caused adhesions and mechanical compression of peripheral nerves, and we conclude that a similar mechanism may be responsible in part for chronic groin pain in humans.

Placement of mesh in direct contact with inguinal nerves is not recommended for avoiding groin pain [2–4, 6–8, 17]. Tsakayannis et al. [31] reported that even elective neurectomy is safe to perform and is not associated with chronic inguinal pain. Our study indicates that preservation of the inguinal nerves is important in mesh herniorrhaphy because of the mesh-induced changes that occur. We conclude that the sensory nerves in the inguinal region should be better separated from the mesh and preserved carefully in order to prevent chronic groin pain when mesh repair is performed. Further studies are needed to evaluate the effect of anatomical position and the relationship of mesh and sensory nerves to chronic pain after herniorrhaphy.

References 1. Lichtenstein IL, Shulman AG, Amid PK, Montllor MM. Cause and prevention of postherniorrhaphy neuralgia: a proposed protocol for treatment. Am J Surg 1988;155:786–790 2. Helse CP, Starling JR. Mesh inguinodynia: a new clinical syndrome after inguinal herniorrhaphy? J Am Coll Surg 1998;187:514–518 3. Bay-Nielsen M, Perkins FM, Kehlet H. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 2001;233:1–7 4. Callesen T, Bech K, Nielsen R, Andersen J, Hesselfeldt P, Roikjaer O, Kehlet H. Pain after groin hernia repair. Br J Surg 1998;85:1412–1414 5. Haapaniemi S, Nilson E. Recurrence and pain three years after groin hernia repair. Vallidation of postal questionnaire and physical examination as a method of follow-up. Eur J Surg 2002;168:22–28 6. Callesen T, Bech K, Kehlet H. Prospective study of chronic pain after groin hernia repair. Br J Surg 1999;86:1528– 1531 7. Ravichandran D, Kalambe BG, Pain JA. Pilot randomized controlled study of preservation or division of ilioinguinal nevre in open mesh repair of inguinal hernia. Br J Surg 2000;87:1166–1167 8. Kumar S, Wilson RG, Nixon SJ, Macintyre IMC. Chronic pain after laparoscopic and open mesh repair of groin hernia. Br J Surg 2002;89:1476–1479 9. Poobalan AS, Bruce J, King PM, et al. Chronic pain and quality of life following open inguinal hernia repair. Br J Surg 2001;88:1122–1126 10. Courtney CA, Duffy K, Serpell MG, et al. Outcome of patients with severe chronic pain following repair of groin hernia. Br J Surg 2002;89:1310–1314 11. The MRC Laparoscopic Groin Hernia Trial Group. Laparoscopic versus open repair of groin hernia: a randomized comparison. Lancet 1999;354:185–190

273 Chapter 36 · The Effect of Polypropylene Mesh on the Ilioinguinal Nerve

12. Seid AS, Amos E. Entrapment neuropathy in laparoscopic herniorrhaphy. Surg Endosc 1994;8:1050–1053 13. Liem MS, van der Graaf Y, van Steensel CJ, et al. comparison of conventional anterior surgery and laparoscopic surgery for inguinal hernia repair. N Eng J Med 1997;336:1541–1547 14. Dirksen CD, Beets GL, Go PM, et al. Bassini repair compared with laparoscopic repair for primary inguinal hernia: a randomized controlled trial. Eur J Surg 1998;164:439–447 15. Hay JM, Boudet MJ, Fingerhut A, et al. Shouldice inguinal hernia repair in the male adult: the gold standard? A multicenter controlled trial in 1,578 patients. Ann Surg 1995;222:719–727 16. Salcedo-Wasicek MC, Thirlby RC. Postoperative course after inguinal herniorrhaphy. A case controlled comparison of patients receiving workers’ compensation vs. commercial insurance. Arch Surg 1995;130:29–32 17. Bower S, Moore BB, Stephen MW. Neuralgia after inguinal hernia repair. Am Surg 1996;62:664–667 18. Wantz GE. Testicular atrophy and chronic residual neuralgia as risks of inguinal hernioplasty. Surg Clin North Am 1993;73:571–581 19. Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy. Pain 1986;3 (suppl):S1–226 20. Campadelli P, Gangai C, Pasquale P. Automated morphometric analysis in peripheral neuropathies. Comput Biol Med 1999;29:147–156 21. Shulman AG, Amid PK, Lichtenstein IL. The safety of mesh repair for primary inguinal hernias: results of 3,019 operations from five diverse surgical sources. Am J Surg 1992; 58:255–257 22. Lichtenstein IL, Shulman AG, Amid PK, Montllor MM. The tension-free hernioplasty. Am J Surg 1989;157:188–193 23. Amid PK, Shulman AG, Lichtenstein IL. Critical scrutiny of the open tension free hernioplasty. Am J Surg 1993; 165:369 24. Arnould JP, Eloy R, Weill-Bousson M, et al. Resistance et tolerance biologique de 6 prostheses insertes utilizes dans la reparation de la paroi abdominale. J Chir 1977; 113:85–100 25. Usher FC, Wallace SA. Tissue reaction to plastic, a comparison of nylon, Orlon, Dacron, Teflon and Marlex. Arch Surg 1958:76:997–1003 26. Walker AP. Biomaterials in hernia repair. In: Nyhus LM, Condon RE (eds). Hernia, 4th edn. Lippincott, Philadelphia, 1995:534–540 27. Uzzo RG, Lemarck GE, Morrissey KP, et al. The effects of mesh bioprosthesis on the spermatic cord structures: a preliminary report in a canine model. J Urol 1999; 161:1344–1349 28. Shin D, Lipshultz LI, Goldstein M, Barme GA, Eugene FF, Nagler HM, McCallum SW, Niederberger CS, Schoor RA, Burgh VM, Honig SC. Herniorrhaphy with polypropylene mesh causing inguinal vassal obstruction: a preventable cause of obstructive azoospermia. Ann Surg 2005;241:553–558

36

29. Lichtenstein IL. Herniorrhaphy Am J Surg 1987;153:553 30. Wagner M. Evaluation of diverse plastic and cutis prostheses in a growing host. Surg Gynecol Obstet 1970;130:1077 31. Tsakayannis DE, Kiriakopoulos AC, Linos DA. Elective neurectomy during open tension free inguinal hernia repair. Hernia 2004;8:67–69

Discussion Amid: Many congratulations on your study. We

were inspired by your work and started doing the same thing on human subjects. We are doing exactly what you did on the nerves that you are removing from patients who have pain. And our preliminary result is completely consistent with your report. The only thing is that because we are doing it on humans, we know that these changes are causing pain, whereas in your rabbits you do not know if they are feeling pain. Your work was inspiration for our ongoing work. On a microscopic point of view, when you remove the mesh with the nerve, did you observe some adhesions of the nerves to the mesh? Demirer: Yes, of course. After 3 months we explored again. Here we observed on the experimental side a very dense fibrotic tissue and adhesion formation as compared to the control side. Smeds: Did you check how far away from the adhesion area the nerves were changed? Did you test it outside of the operation field as well? Demirer: No. Ramshaw: How would you translate this research in terms of clinical patient benefit? Demirer: In my clinic we now only use polypropylene meshes, and 2–5% of patients complain of pain. Schumpelick: What did the neuropathologists say to you about these findings? Have they seen such alterations of nerves before? Demirer: We did not ask the neuropathologists. Deysine: Have you considered conduction studies on those pieces of nerves that you took out? Demirer: In the next studies we should investigate degenerative changes by nerve physiologists. In this study we did not perform such analyses.

37

Lightweight Macroporous Mesh vs. Standard Polypropylene Mesh in Lichtenstein Hernioplasty S. Bringman

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Chapter 37 · Lightweight Macroporous Mesh vs. Standard Polypropylene Mesh in Lichtenstein Hernioplasty

Introduction A standard polypropylene mesh used in Lichtenstein’s operation induces a strong foreign tissue reaction with potential harmful effects [1]. A mesh with less polypropylene and large pores could possibly be beneficial [2]. This chapter summarizes a randomized controlled trial comparing standard mesh and lightweight mesh [3–5].

Discussion

Six hundred men with a unilateral primary inguinal hernia were randomized through a secure Web site to be operated on with a Lichtenstein repair using either a lightweight (LW) macroporous mesh (Vypro II, Ethicon, Hamburg, Germany) or a standard polypropylene mesh (Prolene, Ethicon, Hamburg, Germany). All data were captured through the Web site. The patients were blinded to which mesh they received. Five Swedish and one Finnish hospital participated in the study. The patients completed a diary with SF-36 and visual analog (VAS) pain scales during the first 8 weeks postoperatively. After 1 year, a questionnaire was sent to all patients. Patients who indicated a lump in the groin or another complaint were examined. Three years postoperatively, the patients were examined by a blinded surgeon, and another questionnaire was completed.

In this Internet-based, multicenter study, it was demonstrated that no differences existed between Lichtenstein’s operation with LW mesh or with standard mesh up to 12 months after surgery. However, after 3 years, some aspects of pain and foreign body sensation were noted to be less in the LW group without increasing the rate of hernia recurrence. Other authors have demonstrated similar results concerning pain and foreign body sensation [6, 7]. One study showed an increased risk of recurrence in the LW group [6], which was estimated to be due to factors in the operative technique. In the present trial we used a technique with a running suture, with 1-cm intervals between the large bites in the mesh. We found no difference concerning recurrences between the groups. In conclusion, we found no difference between the group that received LW mesh and the group that received standard polypropylene mesh in Lichtenstein’s hernioplasty up to 12 months postoperatively. The LW mesh did not affect recurrence rates compared with standard mesh, but some aspects of pain and foreign body sensation were improved at follow-up 3 years after surgery.

Results

References

Of the total 600 patients, 301 were randomized to standard mesh and 299 to LW mesh, and 591 were operated on as allocated. The first patient was recruited in mid-December 2000 and the last in April 2002. The groups were comparable with regard to demographic data. There were no differences between the groups concerning return to work or normal activities, SF-36 scores, or VAS pain scores up to 8 weeks or at 12 months. The recurrence rate 3 years after surgery was 3.7% after standard mesh and 3.6% after LW mesh repair. The LW mesh group had less pain when rising from a reclining to a sitting position (p=0.03). Significantly, more men in the standard mesh group

1.

Patients and Methods

37

than in the LW mesh group (p=0.025) stated that they could feel the mesh in their groin.

2.

3.

4.

Klinge U, Klosterhalfen B, Muller M, Schumpelick V. Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 1999; 165(7):665–673 Junge K, Klinge U, Rosch R, Klosterhalfen B, Schumpelick V. Functional and morphologic properties of a modified mesh for inguinal hernia repair. World J Surg 2002; 26(12):1472–1480 Bringman S, Heikkinen TJ, Wollert S, Osterberg J, Smedberg S, Granlund H, et al. Early results of a single-blinded, randomized, controlled, Internet-based multicenter trial comparing Prolene and Vypro II mesh in Lichtenstein hernioplasty. Hernia 2004; 8(2):127–134 Bringman S, Wollert S, Osterberg J, Smedberg S, Granlund H, Fellander G, et al. One year results of a randomised controlled multi-centre study comparing Prolene and Vypro II-mesh in Lichtenstein hernioplasty. Hernia 2005; 9(3):223–227

277 Chapter 37 · Lightweight Macroporous Mesh vs. Standard Polypropylene Mesh

5.

6.

7.

Bringman S, Wollert S, Osterberg J, Smedberg S, Granlund H, Heikkinen TJ. Three-year results of a randomized clinical trial of lightweight or standard polypropylene mesh in Lichtenstein repair of primary inguinal hernia. Br J Surg 2006; 93(9):1056–1059 O’Dwyer PJ, Kingsnorth AN, Molloy RG, Small PK, Lammers B, Horeyseck G. Randomized clinical trial assessing impact of a lightweight or heavyweight mesh on chronic pain after inguinal hernia repair. Br J Surg 2005; 92(2):166–170 Post S, Weiss B, Willer M, Neufang T, Lorenz D. Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair. Br J Surg 2004; 91(1):44–48

Discussion Kurzer: There are three trials now. And in the European guidelines we are asking ourselves if the books are closed on this subject. The recommendation is that the use of lightweight [mesh] can be considered in inguinal hernia repair to decrease postoperative discomfort – but it is also stated that possibly [would be] at the cost of more recurrences. What would be your recommendation? Bringman: Well, I think that the Vypro II is not the best large-pore material available now. If we had UltraPro when we started the trial, we would definitely have used that one. It is true that there are only some aspects where we found a difference in our trial. I also know that the Vicryl portion of Vypro II provokes rather heavy inflammation. So I would expect the results from an UltraPro study to make it clearer in the future Post: Congratulations on the nice study. You mentioned that the design was single-blinded. Does that mean that the examiner knew which type of mesh was implanted, or was the examiner was also blinded? Bringman: The examiner was blinded. Miserez: I presume you now use lightweight in your standard daily practice—and I have two questions on that. First, does this advantage outweigh that of increased costs? Second, do you use it in all patients, or are there patients with a large direct or indirect hernia where you would not use a lightweight mesh? Bringman: In very large defects I would use a heavyweight mesh. Now I do very little Lichtenstein anymore. I focus on laparoscopic hernia surgery.

37

Jacob: There is a study that was recently pub-

lished by Dr. Heniford and Dr. Matthews, and they looked at Ki67 and the continuing cell turnover for the different mesh products—I think they used a rabbit model. They found that the heavyweight product actually had continuing cell turnover at a year compared to the lightweight mesh, where this process actually died off. And so one of the possibilities was that there is an ongoing cellular turnover with these heavyweight products that is contributing to the ongoing symptoms that you found. So the question is with this nerve information from its contact with the mesh. One of my partners opens the floor in all of his open repairs and puts the mesh in the same location as in laparoscopic repair and closes the transverse fascia over so that there is no mesh in contact with the nerves running through the canal. And I wondered if anyone else had thought of or has been doing that and what their outcomes are—so, some sort of Lichtenstein repair in the preperitoneal space. Champault: You are describing an operation described by my chief Jean Rives in 1963. Transinguinal preperitoneal prosthesis, and Volker said it was TIPP, but for me it was the Rives operation. Jacob: Maybe that is the direction where we have to go back to again to avoid the nerve problem, by putting the mesh to this place. Desine: I was very impressed by the mathematical description of your work—I was able to understand it very well—but I am concerned that you had a high incidence of testicular atrophy which I cannot explain except because of technique. And that is what has to be emphasized for the rest of his training. The percentage of testicular atrophy should be below 1%. Bringman: I agree. Schumpelick: When we first used lightweight meshes in the Lichtenstein repair, we had problems in fixing this floppy mesh in front of the pubic bone. Should we use a bigger overlap to avoid a recurrence? Bringman: We made big overlaps and a rather short distance between the stitches. Schumpelick: And additional stitches? Bringman: Additional stitches starting about 2 cm up on the medial side.

38

Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain? B. P. Page and P. J. O’Dwyer

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Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain?

Introduction Chronic pain is the most serious long-term complication of inguinal hernia repair. Up to one-third of patients will complain of some sort of pain at 1 year postoperatively, and in 3–4% of patients this pain will be severe and disabling [1, 2]. The causes of this pain are poorly understood, but factors such as nerve and tissue injury may be important. Psychological factors are also implicated, and more recently, the type of mesh used has been considered [3]. The most frequently used mesh type in inguinal hernia repair is polypropylene based. These meshes can be monofilament or multifilament with a closed or open weave. In some patients they become very stiff over time, and patients complain that they can feel the mesh in their groin, while in others the mesh causes pain [4]. To overcome this, products have been designed that contain an absorbable and a nonabsorbable component [5]. The nonabsorbable polypropylene left in situ usually weighs about one-third that of conventional meshes. The aim of this study was to compare a partially absorbable (PA) product, Vypro II, with a conventional nonabsorbable (NA) polypropylene mesh. The primary end point of the study was pain at 1 year following surgery. This was assessed by visual analogue pain scores and a validated questionnaire [2].

Patients and Methods

38

Ethics committee approval was obtained in five surgical units to randomise patients over 18 years of age with an inguinal hernia to receive either PA or NA mesh using the Lichtenstein repair [6]. Randomisation was computer generated with block sizes that allowed balanced recruitment within each centre. Patients were excluded if the hernia was strangulated or irreducible or if they had undergone an open tension-free mesh repair previously on the same side as the current hernia. Both patients and the staff conducting the postoperative assessments were unaware of the treatment allocated. The PA mesh used in this study was constructed of multifilaments of polypropylene with additional absorbable polyglactin (Vypro II, Ethicon, Ham-

burg, Germany). This mesh has a pore size of 4 mm and weighs 82 g/m2 at implantation and 32 g/m2 after absorption of the polyglactin component, which usually takes 56–70 days. The NA mesh has a pore size of 1 mm and weighs 85 g/m2 (Atrium, Atrium Medical, Schiphol-Rijk, Netherlands). Before operation, pain scores on a visual analogue scale (VAS) were measured in all patients at rest and while moving, and all completed a short-form (SF)-36 questionnaire. Patients underwent open tension-free Lichtenstein mesh repair. Operative details recorded included the hernia type and size, any adverse events, and whether the nerves were identified and preserved or divided. All postoperative complications were recorded, and patients were telephoned with set questions at 10, 20, and 30 days after surgery to determine the incidence of wound infection and other wound-related problems. Patients who reported a wound infection or haematoma were recalled and examined clinically. Hospital stay and time to return to work and normal activities were recorded for all patients. Patients were sent a VAS pain scale at 1, 3, and 12 months, as well as a modified SF-36 questionnaire. Modifications included questions about pain of any severity at the site of hernia repair (none, very mild, mild, moderate, severe, or very severe). Patients were also asked whether the pain was present all of the time, most of the time, some of the time, a little of the time, or none of the time. In addition, they underwent clinical review and examination at 12 months for any evidence of chronic wound problem, testicular atrophy, or development of a recurrent or contralateral hernia. Patients were also asked about any pain or numbness at the site of hernia repair. A sample size of 300 evaluable patients was necessary to ensure an 80% power to detect a benefit of the PA mesh of 15% for primary efficacy (incidence of chronic pain at 12 months: NA mesh, 35%; PA mesh, 20%) at the 5% level of significance using a two-sided test. All subjects, regardless of their compliance with the protocol, were included in the analysis. For efficacy analysis, patients with missing data for pain at 12 months were analysed using the last valid observation, which was carried forward for those who did not complete a questionnaire at that time point. All statistical tests were interpreted

281 Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy

at the 5% significance level, and 95% confidence intervals (CIs) were calculated when appropriate. No adjustment for multiple testing was made.

38

graphics and the anaesthetic and operating details were similar for the two groups (⊡ Table 38.1).

Primary End Point Results Altogether, 333 patients consented to participate in the study. Two patients did not fulfil the inclusion criteria, while 10 either withdrew consent or failed to complete the preoperative assessments. This left 162 patients in the PA mesh group and 159 in the NA group (see ⊡ Fig. 38.1). The patient demo-

There were no differences in pain as rated by the VAS at any of the time points in the study (⊡ Figs. 38.2 and 38.3). Similar numbers of patients reported severe pain in both groups. Pain of any severity was found to be less in the PA group, 39.5% vs. 51.6%, a difference of 12.1% (95% CI: -23.1 to -1.0, p=0.033; see ⊡ Table 38.2).

Consenting patients: 333

Randomised: 330

Partially absorbable (PA) group:N=166

Completed postoperative assessments: 162 (97.6%)

1-month questionnaire: 142 (85.5%)

3-month questionnaire: 125 (75.3%)

12-month questionnaire: 137 (82.5%)

12-month clinic: 142 (85.5%) ⊡ Fig. 38.1. Trial profile

Nonabsorbable (NA) group:N=164

Completed postoperative assessments: 159 (97%)

1-month questionnaire: 135 (82.3%)

3-month questionnaire: 129 (78.7%)

12-month questionnaire: 129 (78.7%)

12-month clinic: 142 (86.6%)

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Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain?

⊡ Fig. 38.2. Visual analogue pain scores at rest in both patient groups preoperatively and 1, 3, and 12 months after surgery (plots are means with 95% confidence intervals)

38

⊡ Fig. 38.3. Visual analogue pain scores on movement in both patient groups measured preoperatively and at 1, 3, and 12 months after surgery (plots are means with 95% confidence intervals)

283 Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy

38

⊡ Table 38.1. Patient demographics and anaesthesia and operating details for the partially absorbable (PA) and nonabsorbable (NA) groups PA group, n=162

NA group, n=159

55.7 (16.4)

57.3 (15.8)

156:6

154:5

25.5 (3.4)

25.7 (3.0)

Site of hernia: Right Left

80 (49.9%) 82 (50.6%)

86 (54.1%) 73 (45.9%)

Type of defect: Direct Indirect Combined

64 (39.5%) 77 (47.5%) 21 (13%)

51 (32.1%) 78 (49.1%) 30 (18.9%)

Size of defect: <1.5 cm 1.5–3 cm >3 cm

27 (16.7%) 74 (45.7%) 61 (37.7%)

24 (15.1%) 68 (42.8%) 65 (40.9%)

Type of anaesthesia: General Local Spinal

90 (55.6%) 64 (39.5%) 8 (4.9%)

94 (59.1%) 62 (39%) 3 (1.9%)

Operating time (min)a

42.5 (17.2)

42.9 (16.6)

Incision length (cm)a

7.4 (1.9)

7.4 (1.5)

Nerves identified: Ilioinguinal Genital Iliohypogastric

145 (89.5%) 74 (45.7%) 10 (6.2%)

146 (91.8%) 77 (48.4%) 68 (42.8%)

Nerves divided: Ilioinguinal Genital Iliohypogastric

32 (19.8%) 13 (8%) 10 (6.2%)

32 (20.1%) 16 (10.1%) 11 (6.9%)

Age (years)a Sex ratio (M:F) Body mass index

aValues

a

are mean (standard deviation)

⊡ Table 38.2. Pain at 12 months in the partially absorbable (PA) and nonabsorbable (NA) groups Any paina

Severe or very severe pain

PA

39.5%

3%

NA

51.6%

4%

aDifference:

12.1% (95% confidence interval -23.1 to -1.0),

common in the PA group (⊡ Table 38.4). There was no statistical difference between groups in terms of occurrence of testicular atrophy, wound sinus, or contralateral hernia when examined at 12 months.

Costs to Health Service

p=0.033

Secondary End Points Return to normal activities was the same in both groups (⊡ Table 38.3). There were six (3.7%) wound infections in the PA group and 10 (6.3%) in the NA group. Hernia recurrence was significantly more

In terms of costs, the PA mesh costs approximately £14.32 more than the NA mesh, and these costs as well as the costs of treating additional recurrences have been calculated in a United Kingdom context. Given that about 70,000 inguinal hernias are repaired each year, this translates to a cost of about £1.4 million to the United Kingdom health service. This will increase to £6.4 million when the cost of treating the extra recurrences is factored in.

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Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain?

⊡ Table 38.3. Time to normal activities in days; values are median (interquartile range) PA group

NA group

p-value (log rank test)

Paid work

21 (14–42), n=82

26 (10–49), n=77

0.375

Housework

10 (5–24), n=161

10 (4–21), n=154

0.579

Social life

10 (5–21), n=161

10 (4–24), n=154

0.622

Sex

28 (14 to >365), n=161

28 (14 to >365), n=154

0.649

Hobbies

20 (10–40), n=161

14 (7–31), n=154

0.283

⊡ Table 38.4. Hernia recurrence at 12 months in the partially absorbable (PA) and nonabsorbable (NA) groups Number

Recurrencea

p (Fisher’s exact test)

PA

142

8 (5.6%)

0.037

NA

142

1 (0.7%)

aAnalysis

performed with respect to those who completed the postoperative assessments

Discussion

38

This study shows that there was no difference in pain scores at rest or with movement between patients randomised to PA or to NA mesh. There was also no difference in severe pain between the two groups. It is likely that the small differences in all types of pain reported in favour of the PA group reflected differences in mild and very mild pain in this study. This finding is in keeping with other studies in which patients were less likely to feel a foreign body in their groin after inguinal hernia repair with Vypro mesh [4]. One of the disappointing results of this study was a significant increase in recurrence rates in the PA group. Subsequent investigation revealed that the reason for this was that the suture pullout force in the knitted direction of the mesh was low (⊡ Fig. 38.4). This may have caused or contributed to the high recurrence rate in the PA group. The manufacturer had stressed that suture bites of at least 1 cm were required with its product. Surgeons used to taking smaller bites of mesh, as is routine with conventional polypro-

pylene mesh, underestimated the consequence of inadequate fixation with Vypro II. This may explain why most of the recurrences–five of eight– were observed in one of the participating centres. Surgeons in this centre admitted that they did not adhere to taking suture bites of at least 1 cm with the PA mesh. The PA mesh used in this study was among the first of its type to be investigated in a randomised clinical trial. The perceived advantage of leaving about one-third of the amount of polypropylene in situ after the polyglactin component is absorbed has been exploited in other products that maintain the tensile strength of the absorbable component for a longer period (e.g. Ultrapro [7]). These products may perform better than Vypro II but need to be evaluated in a similar fashion. Meshes with less polypropylene and a larger pore size, 3–4 mm, should also be evaluated in randomised clinical trials. The in vitro performance of these products may not be matched by what happens in patients. New products, such as polyvinylidene fluoride, that have a similar weight to conventional polypro-

285 Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy

38

⊡ Fig. 38.4. Suture pull-out force

pylene meshes but a larger pore size also require further careful evaluation in long-term follow-up studies [8]. Biological products that are thought to help stimulate growth of normal human blood vessels and collagen have also had limited testing in inguinal hernia repair [6]. One of the drawbacks of the many new products is the increased costs. Some of these products are several times more expensive than conventional polypropylene meshes. It follows, therefore, that a dramatic improvement in the patients’ quality of life, with similar or reduced recurrence rates, would be required to justify their routine use in inguinal hernia repair. While this seems unlikely, the cost to the health service of a product would be reduced if proven advantages resulted in increased use. This study demonstrates no clinical advantage for using a PA mesh in inguinal hernia repair. The significant reduction in mild discomfort that was observed warrants further investigation with dif-

ferent products in larger multicentre controlled clinical trials.

References 1.

2.

3.

4.

5.

Bay-Neilson M, Perkins FM, Kehlet H. Pain and functional impairment 1 year after inguinal herniorrhaphy: a nationwide questionnaire study. Ann Surg 2001; 233:1–7 MRC Laparoscopic Groin Hernia Trial Group. Laparoscopic versus open repair of groin hernia, a randomised comparison. Lancet 1999; 354:185–190 Lagenbach MR, Schmidt J, Zirngibl H. Comparison of biomaterials in the early postoperative period. Polyprolene meshes in laparoscopic inguinal hernia repair. Surg Endosc 2003; 17:1105–1109 Post S, Weiss B, Willer M, Neufang T, Lorenz D. Randomised clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair. Br J Surg 2004; 91:44–48 Junge K, Klinge U, Rosch R, Klosterhalfen B, Schumpelick V. Functional and morphological properties of a modified mesh for inguinal hernia repair. World J Surg 2002; 26:1472–1480

286

6.

7.

8.

Chapter 38 · Does the Choice of Prosthetic Mesh Type Make a Difference in Postherniorrhaphy Groin Pain?

Lichtenstein IL, Shulman AG, Amid PK, Willis PA. Hernia repair with polypropylene mesh, an improved method. AORN J 1990; 52:559–565 Cobb WS, Kercher KW, Heniford BT. The argument for lightweight polypropylene mesh in hernia repair. Surg Innov 2005; 12:63–69 Klinge U. Mesh for hernia repair. Br J Surg 2008; 95:539– 540

Discussion

38

Montgomery: You mentioned the mesh weight, and you said there was a middleweight mesh of 85 g. I just wondered whether this group here has a consensus on what is a lightweight mesh and what a heavyweight mesh. Should we use or call anything midweight meshes? O’Dwyer: Just out of interest, one of our group has decided that less than 40 g/m2 is truly lightweight and between 40 and 80 is middleweight, and if it’s greater than 80 it is heavyweight. But you could also say that if it is lighter than 60 g/ m2 it’s light weight, and if it’s greater than 60, it is heavyweight. Montgomery: Is anyone here having sort of a consensus on this topic? And should we count the mesh weight together with the composite part of it? Hegarty: We have to distinguish between mesh weight and pore size, don’t we? I am not bothered about how much it weighs or about the diameter of the filaments—I want a big-pore mesh. Conze: I think it is not only the weight—forget about the weight. There are meshes that are certainly more heavy than polypropylene. Say, PVDF is more heavy. If you take a PVDF mesh with the same size and the same pore size as a polypropylene mesh, it is going to be a heavyweight mesh. We should focus more on pore size and even more on surface area. And by doing that, we will get to a new classification. O’Dwyer: I think that makes sense. Pore size and filament type are perhaps more important. Unfortunately, we have gone down this route for the last 10 years. Schumpelick: The question is if we need a new technique for these lightweight flexible meshes. We have learned that with the ventral hernia we

had mistakes here, and we have to make more overlap. The question to Bringman was that without enough overlap at the pubic bone, we have problems. We need an optimized technique for these new meshes. O’Dwyer: We need a product that is forgiving. Simons: How can there be 60 randomized in one group and only 48 in the other? What kind of randomization system did you have? O’Dwyer: It was a computer-generated randomization by our statisticians. Every single patient was entered again as a new entry—it was not a block randomization.

39

New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia and Orchialgia P. K. Amid

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Chapter 39 · New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia

Introduction Advances in inguinal hernia repair, such as the use of prosthetic materials and new techniques, have markedly reduced the postherniorrhaphy recurrence rate. However, chronic pain after hernia repair is of continuing concern. According to the Swedish Hernia Registry, the incidence of chronic pain postherniorrhaphy is greater than that of hernia recurrence [1]. We have previously described the causes, prevention, and surgical treatment of postherniorrhaphy chronic pain [2]. The current study of groin neuroanatomy has resulted in new understanding of certain features of postherniorrhaphy inguinodynia and orchialgia. Our series now stands at 465 patients who have undergone operation for chronic post hernia repair groin pain intractable to nonsurgical pain management treatment. Recent observations of groin neuroanatomy have prompted a modification of our neurectomy technique to include a more extensive resection of the iliohypogastric nerve and, for patients with orchialgia, resection of nerves within the lamina propria of the vas deferens as well. These observations also illustrate methods to avoid nerve injuries in the original hernia operation.

than dividing the nerve as it emerges from the internal oblique muscle, as was our practice previously, the nerve was followed and severed proximal to the surgical field of the original hernia repair. In 21 of those patients, the intramuscular segment of the iliohypogastric nerve was scarred by perineural fibrosis or entrapped by sutures placed when the so-called conjoined tendon was sutured to the inguinal ligament, plug, or flat mesh, depending on the method of the original hernia repair. In less than 5% of patients, the iliohypogastric nerve is under the internal oblique aponeurosis in the inguinal region. During hernia repair in these patients, the subaponeurotic course of the nerve must be determined by noting the

Methods

39

Between 1995 and 2008, the triple neurectomy operation was performed on 465 patients who did not respond to nonsurgical pain management treatment. These patients either did not have pain prior to their original hernia repair or, if they did, their postoperative pain was different from their preoperative pain and had the characteristic features of neuropathic pain according to the International Association for the Study of Pain. The interval between the original hernia repair and triple neurectomy was 2–5 years. In 210 patients who underwent triple neurectomy from 2004 to 2008, attention was focused on the intramuscular segment of the iliohypogastric nerve, the most vulnerable neural structure within the operative field. A slit was made in the internal oblique muscle fibers to expose the intramuscular segment of the iliohypogastric nerve (⊡ Fig. 39.1). Then, rather

⊡ Fig. 39.1. Intramuscular segment of the iliohypogastric nerve exposed by splitting the muscle fibers (with sutures retracting the edges of split)

⊡ Fig. 39.2. Point of simultaneous passage of a subaponeurotic iliohypogastric nerve from both external and internal oblique aponeurosis

289 Chapter 39 · New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy

location of its exit at the small point of attachment between the internal and external oblique aponeuroses (⊡ Fig. 39.2), and the surgeon should avoid placing sutures or staples below the abovementioned point because the course of the nerve under the internal oblique aponeurosis is inferior and lateral (⊡ Fig. 39.3). During triple neurectomy, the subaponeurotic iliohypogastric nerve can be identified by splitting the internal oblique aponeurosis immediately below the aforementioned point (⊡ Fig. 39.3). In early 2005, a patient was referred with chronic groin pain and orchialgia, and a magnetic resonance scan showed the vas deferens entrapped by a plug (⊡ Fig. 39.4). At operation, the plug completely encircled the vas deferens (⊡ Fig. 39.5). Because the patient had undergone an earlier vasectomy, the entrapped segment of the vas was resected during the triple neurectomy. Postoperatively, the patient’s groin pain and orchialgia disappeared, which was contrary to our experience with other patients with both groin pain and orchialgia who had undergone triple neurectomy alone. Histological study showed fibrosis and foreign body reaction around the paravasal nerves within the lamina propria of the vas (⊡ Fig. 39.6). In 11 subsequent patients with groin pain and orchialgia combined, a 2-cm segment of the lamina propria of the vas was resected (without resecting the vas) as proximal to the internal ring as possible. Histology showed perineural fibrosis in these patients as well.

39

⊡ Fig. 39.3. Subaponeurotic iliohypogastric nerve exposed by splitting the internal oblique aponeurosis

⊡ Fig. 39.4. Magnetic resonance image showing entrapment of vas deferens by a plug

Results From 1995 to 2008, 460 patients with chronic postherniorrhaphy pain underwent surgical treatment at the Lichtenstein Hernia Institute in Santa Monica, California. In 180 patients who had most recently undergone triple neurectomy, particular attention was paid to the intramuscular portion of the iliohypogastric nerve. Adding resection of the intramuscular segment of the iliohypogastric nerve improved the success rate of triple neurectomy compared with division of the iliohypogastric nerve at the point of its emergence from the internal oblique muscle. Furthermore, adding

⊡ Fig. 39.5. Explanted plug along with the entrapped segment of vas from Fig. 39.4

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Chapter 39 · New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia

⊡ Fig. 39.6. Perineural fibrosis of paravasal nerves corresponding to Figs. 39.4 and 39.5

resection of the lamina propria of the vas to triple neurectomy eliminated testicular pain.

Discussion

39

The definition of chronic inguinodynia, its diagnostic criteria, preoperative workup, and intraoperative verification, as well as the surgical treatment and postoperative follow-up, have been described previously [2]. Triple neurectomy is a proven surgical treatment for chronic postherniorrhaphy pain that is intractable to multidisciplinary pain management. According to three major series, the success rate of the operation ranges from 80% [3] to 95% [2, 4]. Resecting the intramuscular portion of the iliohypogastric nerve, instead of severing the nerve at the point of its emergence from the internal oblique muscle, improves the outcome of triple

neurectomy. Although a firm conclusion should not be drawn from such a small number of cases, it seems that resection of the paravasal nerves is a useful addition to triple neurectomy for patients with orchialgia associated with inguinodynia. Pain after placement of mesh in the parietal compartment of the preperitoneal space (during both open and laparoscopic hernia repair) presents special problems. The main trunk of the genitofemoral nerve, the preperitoneal segment of its genital branch, and its femoral branch located in the parietal compartment of the preperitoneal space have no fascial coverage to protect them from direct contact with nerves. This is in contrast to the nerves in front of the transversalis fascia, where the ilioinguinal and iliohypogastric nerves are covered by the investing fascia of the internal oblique muscle, and the inguinal segment of the genital branch is covered by the deep cremasteric

291 Chapter 39 · New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy

fascia. These covering layers protect the nerves by acting as a barrier against the mesh. There is experimental evidence that direct contact of mesh with the nerves leads to certain ultrastructural changes in the nerves; this evidence is consistent with the preliminary results of our ongoing study of the structural changes of nerves in patients suffering from postherniorrhaphy pain. Also, because the nerves within the preperitoneal space are not easily accessible during operative exploration, surgical treatment of inguinodynia and orchialgia after preperitoneal hernia repair is less likely to improve the patient’s symptoms. Therefore, we reserve triple neurectomy for pain after laparoscopic hernia repair for patients in whom staples or tacks were used and for those in whom computed tomography or magnetic resonance imaging shows meshoma. Recently we proposed a possible treatment for neuropathy following open and laparoscopic preperitoneal repair by transabdominal retroperitoneal transection of periinguinal nerves over the psoas muscle [5]. This approach, which can be referred to as transabdominal retroperitoneal triple neurectomy, is currently used for laparoscopic aortic surgery. In light of these new findings, the following recommendations are added to those previously suggested for preventing postherniorrhaphy inguinodynia [2]: 1. Avoid passing sutures through the internal oblique muscle. 2. Avoid suturing the upper edge of the mesh to the internal oblique muscle during Lichtenstein tension-free hernia repair. 3. Avoid mesh implantation in the parietal compartment of the preperitoneal space; within the inguinal canal a layer of fascia acts as a barrier between the nerves and the mesh, but in the parietal compartment of the preperitoneal space, there is no investing fascia to protect the nerves from direct contact with the mesh. 4. Avoid removing the cremasteric layer in order to protect the inguinal segment of genital and paravasal nerves from direct contact with the mesh and thereby avoid postherniorrhaphy inguinodynia, orchialgia, and the possibility of infertility due to direct contact between the mesh and the vas deferens.

39

Failing to identify and protect the nerves during hernia repair significantly increases the incidence of postherniorrhaphy pain [6–8]. Yet this issue has not received due attention. According to the Netherlands Hernia Registry, only 32% of surgeons identified the iliohypogastric nerve during hernia repair, and only 36% identified the genital branch of the genitofemoral nerves. As has been reported by many authors [9], identification and careful attention to the groin nerves during hernia repair reduce the incidence of chronic pain to less than 1%.

References 1.

2.

3.

4.

5. 6.

7.

8.

9.

Franneby U, Sandblom G, Nordin O, Gunnarsson U (2006) Risk factors for long-term pain after hernia surgery. Ann Surg 244:212–219 Amid PK (2004) Causes, prevention, and surgical treatment of postherniorrhaphy neuropathic inguinodynia: triple neurectomy with proximal end implantation. Hernia 8:343–349 Madura JA, Copper CM, Worth RM (2005) Inguinal neurectomy for inguinal nerve entrapment: an experience with 100 patients. Am J Surg 189:283–287 Starling JR, Harms BA (1994) Ilioinguinal, iliohypogastric, and genitofemoral neuralgia. In: Bendavid R (ed) Prostheses and abdominal wall hernia. RG Landes, Austin, pp 351–356 Amid P, Hiatt JR (2008) Surgical anatomy of the preperitoneal space. J Am Coll Surg 207:295 Alfieri S, Rotondi F, Di Giorgio A, et al. (2006) Influence of preservation versus division of ilioinguinal, iliohypogastric, and genital nerves during mesh herniorrhaphy: prospective multicentric study of chronic pain. Ann Surg 243:553–558 Wijsmuller AR, van Veen RN, Bosch JL, Lange JFM, Kleinrensink GJ, Jeekle J, Lange JF (2007) Nerve management during open hernia repair. Br J Surg 94:17–22 Aasvang EK, Mohl B, Bay-Nielson M, Kehlet H (2006) Pain related sexual dysfunction after inguinal herniorrhaphy. Pain122:258–263 Kingsnorth AN, Bowley DMG, Porter C (2003) A prospective study of 1000 hernias: results of the Plymouth Hernia Service. Ann R Coll Surg Engl 85:18–22

Discussion Klinge: Why do you believe that a proper fixation

can prevent the development of mesh shrinkage or mesh migration or meshoma? We have seen so many meshes after some times, despite thousands

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Chapter 39 · New Understanding of the Causes and Surgical Treatment of Postherniorrhaphy Inguinodynia

of tacks. Why do you think that some sutures can prevent this development? Amid: You are right. This usually happens in the preperitoneal space, because the fixation is not complete and the surface is not completely smooth. Very rarely you can see these meshomas in front of the transversalis fascia. And maybe light meshes could prevent that. I do not know. But theoretically, it makes sense to assume that light meshes, by creating less fibrotic tissue, may prevent meshoma formation. Kehlet: You have operated on 460 patients now. Do you find these abnormalities every time you operate? What is the specific indication for these operations? Secondly, neurosurgeons have done neurosurgery for chronic pain for many years— always disappointing. What is the follow-up here? What happens with time? Do you really think that you have solved the problem in the long term? Amid: First, I tell you about the follow-up: We see these patients 1 week and 1 month after the operation and then up to 6 months. We contact them by phone, and that is the end of our follow-up. I admit, this is not a complete follow-up. After the last telephone conversation—and they tell us they are satisfied—if their pain comes back or becomes more, they would contact us. I agree, that is not scientific enough. How often we find these pathologies? Almost all of the time! The least thing that we find is very dense fibrotic tissue—histologically, perineural fibrosis. Now we study the structural changes of the nerves. Penkert: With your large experience in these cases, I wonder that you have success in all cases. So, we must estimate preoperatively what kind of pain it is. If it is neuroma pain, it works. But if it really is a neuropathic pain, it is quite another thing. I am in doubt. That is my comment. Amid: The best indication for this operation is when the previous operation is an anterior repair without manipulation of the preperitoneal space. If the preperitoneal space is manipulated, even by placement of a plug or by placement of a PHS or by a preperitoneal repair, then the pain could be related to the nerves in front of the transversalis fascia or behind the transversalis fascia. And there is no way to find out what part is belonging to the front and what part belongs to behind.

40

Surgery for Chronic Inguinal Pain: Neurectomy, Mesh Explantation, or Both? G. D. Arlt, U. Huhn, C.C. Kersten

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Chapter 40 · Surgery for Chronic Inguinal Pain: Neurectomy, Mesh Explantation, or Both?

Introduction

40

Chronic inguinal pain is a rare but severe complication of inguinal hernia repair, with a prevalence of disabling pain from 3% to 9% (Kehlet et al. 2002, Aroori and Spence 2007). Its exact cause and lack of evidence-based treatment path presents problems in the effective management of this surgical complication. Most cases may be treated conservatively with repeated injections of cortisone and a local anesthetic for a permanent local nerve block. About 70–80% of the patients respond to the infiltration therapy to the point of maximum tenderness (Aroori and Spence 2007, Palumbo et al. 2007). In the others, different treatment strategies have been proposed, such as analgesics and antidepressants, transcutaneous electrical neural stimulation, or recurrent surgery with neurolysis and neurectomy with or without removal of the mesh. Although the necessity of repeated surgery for chronic pain after mesh repair may be rather low, at about 0.35% (Delikoukos et al. 2008), there is major disagreement concerning both the selection criteria for recurrent surgery and the type of surgery itself. Considering the chronic postherniorrhaphy pain syndrome in detail, two types of pain can be distinguished: 1) neuropathic pain caused by entrapment of the ilioinguinal, iliohypogastric, or genital branch of the genitofemoral nerve, and 2) nonneuropathic pain, which might be triggered by staples to the periosteum and/or compression and scar formation around the implanted mesh materials. The latter type of pain may be further differentiated into nociceptive or somatic pain induced, for example, by staples, and visceral pain such as dysejaculation or testicular pain (Loos et al. 2007, Kehlet 2008). In patients with neuropathic pain, a surgical approach with neurectomy of the involved nerves seems rational. Several studies have been published reporting the results of dual or triple neurectomy for chronic groin pain following inguinal hernia surgery. Success rates vary from about 60% to 80% in most series (⊡ Table 40.1). Unfortunately, several of these studies are judged to be of poor quality due to nonstandardized selection criteria, short follow-up, and small sample sizes.

⊡ Table 40.1. Results of neurectomy for chronic groin pain after inguinal hernia repair n

Mesh

Success

Follow-up

Stulz and Pfeiffer 1982

23

0

70%

?

Starling et al. 1987

30

0

83%

?

Kennedy et al. 1994

23

0

63%

36–144 months

Bower et al. 1996

15

0

80%

66 months

Skandalakis 1996

6

0

100%

?

Heise and Starling 1998

9

100%

56%

16 months

Amid 2004

225

100%

80%

–

Madura et al. 2005

100

27%

72%

1–60 months

Ducic et al. 2008

19

100%

84%

12 months

In cases of chronic pain after mesh repair which cannot be assigned to a distinct nerve, the considered surgical approach is mesh removal with or without additional neurectomy. Two small series of mesh removal for pain after groin hernia surgery have been published. In 1998 Heise and Starling described transinguinal mesh removal in 20 patients with severe groin pain following Lichtenstein or laparoscopic mesh repair. The outcome was excellent or good in 12 (60%) of the 20 cases. Aside from a tendency to see better results after additional neurectomy during mesh removal, they were unable to identify other factors that could improve postoperative results or help select better patients for surgery (Heise and Starling 1998). Rosen et al. presented their experience with mesh explantation on the basis of 10 cases selected from 1998 to 2004. The indication was chronic groin pain not responding to local anesthesia of the inguinal nerves. The index operation was a Lichtenstein procedure in nine of the 10 cases. In contrast to Heise and Starling, they used a combined surgical

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procedure with transinguinal removal of the mesh and laparoscopic repair of the hernia defect. Results were good or excellent in nine of 10 patients (Rosen et al. 2006). Our own experiences with indications, operative technique, and results of revision surgery for chronic groin pain after inguinal hernia repair are presented here.

Patients and Methods Patient Selection Patients with persistent or recurrent disabling pain interfering with daily activities 3 months after the index operation were judged as chronic pain cases. Pain of other origin, including hernia recurrence, was ruled out by pain history, clinical and ultrasound examination, and, in some cases, magnetic resonance imaging. Initial treatment was conservative and consisted of oral analgesics and infiltration therapy with local anesthetics and steroids. Those who did not respond to this treatment were candidates for surgery. Patients with neuropathic pain responding to diagnostic nerve block with local anesthetics (10 ml of Xylocaine 1% at the anterior superior iliac spine) were offered revision surgery with dual or triple neurectomy. Those with nonneuropathic pain exhibiting no significant pain relief after nerve block were candidates for mesh removal and neurectomy.

Patients From October 1998 to December 2007, 87 patients with chronic groin pain not responding to conservative treatment were referred for further surgery at the surgical department of the Park-Clinic in Berlin-Weissensee, Germany. Fifty-four patients with severe neuropathic complaints following an inguinal hernia repair were identified for recurrent surgery with double or triple neurectomy: 34 men and 20 women with an average age of 47 (range 14–77) years. Thirtyone cases presented after primary repair, and 23 patients had had several hernia repairs. A non-

40

mesh procedure had been done in 29 patients, and 25 had had a mesh repair. The nonneuropathic pain group consisted of 33 patients (26 male, seven female) with an average age of 48 (range 14–71) years. They were offered a mesh removal procedure. The mesh procedures done previously were a transabdominal preperitoneal or totally extraperitoneal repair in 23 patients, a Lichtenstein repair in five, and a mesh-plug repair in another five cases. Several attempts at conservative treatment on an outpatient basis had been made for all of the patients. In some cases, psychosomatic therapy had been recommended. Patients with mild or moderate symptoms responding to conservative therapy were not included in this series.

Operative Technique In patients dedicated for neurectomy, the lateral part of the skin scar in the groin was opened and the deep inguinal ring exposed. After exclusion of a recurrent hernia, the ilioinguinal and iliohypogastric nerves were identified lateral to the deep ring. Both nerves were resected, and a 1-cm strip of nerve tissue was harvested for histologic examination. The proximal ends of the nerves were embedded in the internus muscle. In cases with triple neurectomy, the genital branch of the genitofemoral nerve was identified at the »blue line« near the deep ring and was resected together with the external spermatic vessels. The surgical technique of mesh removal has been described before (Arlt et al. 2003).

Perioperative Care and Follow-Up Informed consent was given by all patients regarding an increased risk of intraoperative and postoperative complications (estimated percentage of ischemic orchitis about 5%, vascular injury about 5%, and recurrent hernia up to 10%). A single-shot antibiotic prophylaxis was used in all operations. All patients were mobilized within 4–6 h postoperatively. Patients were discharged according to their own wishes between days 2 and 10. Physical

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Chapter 40 · Surgery for Chronic Inguinal Pain: Neurectomy, Mesh Explantation, or Both?

activity was restricted for 2 weeks after hospital discharge. All patients were followed for at least 6 months postoperatively. The last follow-up examinations with clinical assessment and ultrasound were done in June 2008, with the follow-up interval ranging from 6 to 86 months. Results were classified as good for satisfied patients with complete pain relief and no need for further analgesic medications. Satisfied patients with some pain during physical activity and the need for painkillers on demand not more than once or twice a week were classified as having a fair result. A bad outcome was quoted in dissatisfied cases with persisting or recurrent disabling pain after the revision surgery.

sified as having a fair result. In seven cases, the pain persisted or returned within 6 months after the operation. Detailed analysis of the cases with intermittent or persisting pain showed that an adverse outcome (fair or bad) was more likely in younger patients and those who had repair for a recurrent hernia (⊡ Table 40.2). Further surgery with a triple neurectomy or a secondary mesh removal was done in six patients. Consideration of the risk of further surgery with mesh removal in patients with neuropathic pain and a mesh repair in their history showed a 20% risk for additional operations in this subgroup (five of 25 cases).

Mesh Removal Results Neurectomy In the group having neurectomy surgery, no severe intraoperative or postoperative complications occurred. All 54 patients could be followed at least 6 months postoperatively. Forty-two patients showed a good result with no complaints and no analgesic medication at the follow-up examination after 6 months. Another five patients were also satisfied with the surgery but reported intermittent pain during physical activity requiring analgesics once or twice a week. They were clas-

⊡ Table 40.2. Results of neurectomy in 54 patients with neuropathic pain; cases with intermittent or persisting pain (fair or bad results of surgery) were summarized as nonresponders

40

Nonresponders

12/54 (22%)

After primary repair

3/31 (10%)

After recurrent repair

7/25 (28%)

Age >50 years

3/25 (12%)

Age <50 years

7/29 (24%)

Further surgery

6/54 (11%)

Secondary mesh removal

5/25 (2%)

In the group receiving mesh removal, complete or near total explantation of the foreign body was achieved in 32 of 33 patients. In one man with a previous Lichtenstein repair, the mesh removal was impossible due to extended scar formation at the cord, indicating a high risk for testicular atrophy. The surgery was restricted to a dual neurectomy with a fair result 6 months after the operation. In the other 32 patients, one case each of partial resection of the bladder, resection of the small bowel, suture of the femoral vein, seroma formation, and ischemic orchitis with testicular atrophy were the major intraoperative and postoperative complications. Reconstruction of the posterior wall was done with a two-layer Shouldice procedure in 25 cases and a Lichtenstein repair using a lightweight mesh (Vypro II /Ultrapro) in six cases. In a 57-year-old woman, the excision of the mesh– fascia–muscle specimen resulted in a large defect of the posterior wall, which had to be closed by a Rives procedure with a Vypro II mesh. Macroscopically, all mesh specimens showed extended folding and shrinkage of 50–70% of the surface (⊡ Figs. 40.1 and 40.2). Analysis of the mesh material and the histopathologic examination of the explanted foreign bodies showed that 30 meshes were heavyweight (>90 g/m2) polypropylene meshes and two were polyester meshes. Chronic inflammation and apoptosis were regular findings at the mesh–tissue interface.

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At follow-up 6 months to a maximum of 86 months postoperatively, two recurrent inguinal hernias were found. Twenty-two patients had no complaints and were completely satisfied (69% good results). In seven cases, the patients were satisfied but had intermittent pain during physical activity (22% fair results). In one of these patients, a recurrence was found and repaired. During further follow-up, this patient again had a fair outcome. Three patients were dissatisfied (9% bad results). One developed a testicular atrophy, another a symptomatic recurrent hernia, and another complained of persisting disabling pain (⊡ Table 40.3).

⊡ Fig. 40.1. Polypropylene Hernia System prosthesis from a 17-year-old girl 11 months after implantation

⊡ Fig. 40.2. Heavyweight small-pore polypropylene prosthesis 18 months after a transabdominal preperitoneal repair

⊡ Table 40.3. Results of mesh removal for chronic pain: follow-up at 6–86 months Follow-up in June 2008 (clinical exam/ultrasound)

n=32

Recurrent hernia

n= 2

No complaints/satisfied

n=22 (69%)

Pain during physical activity

n=7 (22%)

Dissatisfied (testicular atrophy/ recurrence/persistent pain)

n=3 (9%)

Conclusion The series of 87 patients surgically treated for chronic postherniorrhaphy pain shows that a good or fair clinical result with a satisfactory outcome can be achieved in up to 85% of cases. An important supposition is careful selection of patients. Indication should be restricted to cases with conservatively intractable symptoms. At present, the distinction between neuropathic and nonneuropathic pain on the basis of local nerve blocks can be recommended. The mesh removal operation is challenging, and the surgeon should also be experienced in hernia and vascular surgery. Informed consent from the patient concerning the increased risk of testicular and vascular complications is necessary. To develop a standardized surgical approach regarding chronic groin pain after hernia repair, a large multicenter study would be indispensable.

References Amid PK (2004) Causes, prevention, and surgical treatment of postherniorrhaphy neuropathic inguinodynia: triple neurectomy with proximal end implantation. Hernia 8:343–349 Arlt G, Lamm T, Klosterhalfen B (2003) Mesh removal in inguinal hernia repair. Eur Surg 35:42–44 Aroori S, Spence RA (2007) Chronic pain after hernia surgery–an informed consent issue. Ulster Med J 76:136– 140

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Bower S, Moore BB, Weiss SM (1996) Neuralgia after inguinal hernia repair. Am Surg 62:664–667 Delikoukos S, Fafoulakis F, Christodoulidis G et al. (2008) Reoperation due to severe late-onset persisting groin pain following anterior inguinal hernia repair with mesh. Hernia 12:593–595 Ducic I, West J, Maxted W (2008) Management of chronic postoperative groin pain. Ann Plast Surg 60:294–298 Heise CP, Starling JR (1998) Mesh inguinodynia: a new clinical syndrome after inguinal herniorrhaphy? J Am Coll Surg 187:514–518 Kehlet H (2008) Chronic pain after groin hernia repair. Br J Surg 95:135–136 Kehlet H, Bay-Nielsen M, Kingsnorth A (2002) Chronic postherniorrhaphy pain–a call for uniform assessment. Hernia 6:178–181 Kennedy EM, Harms BA, Starling JR (1994) Absence of maladaptive neuronal plasticity after genitofemoral-ilioinguinal neurectomy. Surgery 116:665–670; discussion 670–671 Loos MJA, Roumen RMH, Scheltinga MRM (2007) Classifying postherniorrhaphy pain syndromes following elective inguinal hernia repair. World J Surg 31:1760–1765 Madura JA, Madura JA II, Copper CM, Worth RM (2005) Inguinal neurectomy for inguinal nerve entrapment: an experience with 100 patients. Am J Surg 189(3):283–287 Palumbo P, Minicucci A, Nasti AG et al. (2007) Treatment for persistent chronic neuralgia after inguinal hernioplasty. Hernia 11:527–531 Rosen MJ, Novitsky YM, Cobb WS, Kercher KW, Heniford BT (2006) Combined open and laparoscopic approach to chronic pain following open inguinal hernia repair. Hernia 10:20–24 Skandalakis JE, Skandalakis LJ, Colborn GL (1996) Testicular atrophy and neuropathy in herniorrhaphy. Am Surg 62:775–782 Starling JR, Harms BA, Schroeder ME, Eichman PL (1987) Diagnosis and treatment of genitofemoral and ilioinguinal entrapment neuralgia. Surgery 102:581–586 Stulz P, Pfeiffer KM (1982) Peripheral nerve injuries resulting from common surgical procedures in the lower portion of the abdomen. Arch Surg 117:324–327

Discussion

40

Deysine: It is evident that these are sometimes true catastrophes, implying very difficult surgery. I am not surprised about the complications that you have. Referring to your paper and the paper of Dr. Amid, there is an alternative thing that we can teach to our residents when we do this hernia surgery: that you do not need to tie knots extremely hard so that you strangulate the tissue. If you teach

your residents to just approximate the mesh to whatever structure you are using, if you have the poor luck of having a nerve in between, it is not going to be strangled, and the patient will not have pain. Because otherwise, going after those nerves is difficult. Again, the technique is a very important aspect for having good results. Schumpelick: I congratulate you. I think it is one of the ugliest operations of all. You must inform your patients about the loss of sensitivity, bleeding of the vein, about the big hole you left and that you have to close maybe with a new mesh. And you must give him the message that at least 20% will have pain. If patients agree with that, he really must have pain. Even in younger people. In my personal experience, they will even come if you say that they might lose their testes. We have at least once a month such a patient. Champault: Two years ago, I saw a young man with pain. I explained the risk of infertility because he had a hernia on the other side when he was 2 years old. So he said okay, and he came back 2 weeks ago with a young boy. To sum up, he postponed the operation for one girl and one boy. Kehlet: Apparently you did a local anesthetic block to divide your indication toward neurectomy or mesh removal. What is the rationale for that, because if you think the pain is coming from the mesh, a local anesthetic block should also help? Arlt: I do not believe that the pain always originates from the mesh. Kehlet: Why did you remove it? Arlt: Only in those cases where they had a meshoma, because when we started this series we followed strictly the idea of having responders to local anesthesia [receive] nerve cutting and nonresponders [receive] mesh removal. We saw that we had five patients with pain responding to local anesthesia who had to have a third operation to take out the meshoma. Kehlet: But my question is, if you believe that the pain is coming from the mesh or the meshoma, why shouldn’t a good anesthetic block work? Arlt: Yes, it works, but only for some hours. It was a diagnostic local anesthesia. We also do this injection therapy, and we have at least 60–70% of patients we do not have to operate on. Thirty percent come again and again, despite injection therapy.

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Results of Tailored Therapy for Patients with Chronic Inguinal Pain M. Stumpf, D. Kämmer, U. Klinge

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Chapter 41 · Results of Tailored Therapy for Patients with Chronic Inguinal Pain

The onset of chronic inguinal pain has been increasing in recent years, but therapeutic options for these patients remain unclear. Different methods apart from conservative management have been described for dealing with this problem. These options include local revision of the scar and the inguinal nerves, with the next step being retroperitoneal triple neurectomy. Patients with an implanted mesh have the option to have the mesh material explanted, but this can sometimes be a rather difficult operation. We analyzed patients treated surgically for chronic inguinal pain in the surgical clinic of the University of Aachen (Germany) between 2005 and 2008. Thirty-three of these patients were included in the study. All patients had to fill out a structured pain questionnaire (Deutscher Schmerzfragebogen). In addition, immunohistochemical investigations of explanted nerves and meshes were done. Most patients had experienced complaints for more than 2 years. Seventy-five percent of patients with chronic inguinal pain had had a mesh repair in the past, mainly Lichtenstein or a laparoscopic procedure. The aim of the study was to analyze which patients would benefit from an operative approach and to learn whether it is possible to distinguish between two types of chronic inguinal pain and whether there are any clinical implications for the therapeutic strategy. For treatment, we chose three different types of surgery: local revision of the scar and nerves, retroperitoneal triple neurectomy (⊡ Fig. 41.1), or explantation of the mesh. The explanted meshes were mainly heavyweight flat meshes and plugs (⊡ Fig. 41.2). The best results were achieved for patients treated by complete mesh explantation: 75% were pain free or had real improvement in their pain. No patient was pain free after local revision, and 50% had persistent pain (⊡ Table 41.1). We then hypothesized that two types of chronic inguinal pain exist. Type I is not curable with operative intervention, but type II will possibly benefit from operative intervention. Therefore, a differentiation was made among the patients: Group 1 patients were pain free or had an improvement in their pain after operation, and

⊡ Fig. 41.1. Retroperitoneal triple neurectomy

⊡ Fig. 41.2. Explanted mesh plug and flat mesh

⊡ Table 41.1. Results after different operations Local revision

Explantation

Neurectomy

Pain-free

0%

50%

25%

Improvement

50%

25%

50%

Persistent pain

50%

25%

25%

those in group 2 had persistent pain after operation. Seventy percent of the male patients improved, but only 55% of the female patients did. There were no statistically significant differences between the two groups with regard to age, obesity, duration of pain, days of hospital stay, or number of previous operations (⊡ Table 41.2). Looking at the types of explanted meshes, it is interesting that all patients

301 Chapter 41 · Results of Tailored Therapy for Patients with Chronic Inguinal Pain

⊡ Table 41.2. Differences between patients who improved after surgery and those with persistent pain Improvement

Persistent

Age

51.16±13.93

43.17±13.97

Obese

8

4

Duration of pain (months)

25±19.4

45±51.5

Days at hospital

12.9±14.2

11.42±6.5

Former operations (n)

1.8±1.0

1.58±1.0

with plug repairs were pain free after mesh explantation. Both groups showed significant differences in the immunohistochemical expression of CD68 and matrix metallopeptidase 2 (MMP2) at the nerve tissue, which may hint at existing differences in the ultrastructure of the two types of patients. In conclusion, patients receive only minor benefits from local revision of the scar and inguinal nerves. The best results, yielding a high number of pain-free patients after the revision, were reached after mesh explantation. All patients who underwent plug removal were pain free. There might be a correlation between the type of patient and the benefit experienced; patients who were pain free after their operation showed differences in immunohistochemical markers compared with the patients who did not benefit from surgery. Further investigation will be necessary to elucidate these interesting findings concerning chronic inguinal pain after hernia surgery.

Discussion Gryska: When you do an explantation, are not also

doing at least a partial neurectomy? Stumpf: Indeed, if you are doing a reoperation fol-

lowing a Lichtenstein hernia repair to also remove the ilioinguinal nerve while the mesh explantation if the nerve wasn’t dissected while the first operation. Gryska: What are you doing with the hernia after explantation of the mesh?

41

Stumpf: We fix the hernia as well. It depends on the age of the patients. If you have a young patient with comparable stable tissue we do a Shouldice repair. But after a TAPP or TEP hernia repair you mainly have a large defect of the abdominal wall. In those cases we usually use large pore and low weight meshes to fix it again. Köckerling: How do exclude a recurrence? And do you use a diagnostic laparoscopy? Stumpf: We use the ultrasound in every patient with inguinal pain. However at first we try to diagnose a recurrence clinically followed by an ultrasound. In case of an experienced investigator you can objectify a recurrence very exactly. A diagnostic laparoscopy was used in some cases, but we didn’t use it routinely.

IV

IV

Risk for Adhesion

42

Adhesion as a Chronic Inflammatory Problem? Risk for Adhesions, Migration, and Erosions? – 305

43

Biological Tissue Graft: Present Status – 317

44

IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis – 323

45

Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual – 331

46

Tissue Ingrowth, Adhesion, and Mesh Contraction

47

Effect of Different Mesh Materials on Adhesion Formation – 353

48

Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature – 365

49

Porosity and Adhesion in an IPOM Model – 375

50

Benefit of Lightweight and/or Titanium Meshes? – 381

51

ePTFE Prostheses and Modifications

52

The Role of Stem Cells in Abdominal Wall Repair – 401

– 345

– 393

42

Adhesion as a Chronic Inflammatory Problem? Risk for Adhesions, Migration, and Erosions? M. Binnebösel, K. Junge, C. D. Klink, J. Serno, J. Otto, J. Conze, A. P. Öttinger, V. Schumpelick

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Introduction

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Peritoneal adhesions are common and develop postoperatively in more than 90% of patients following abdominal surgery. Most adhesions are not symptomatic, however. Even years after surgery, adhesions can lead to undesirable outcomes such as small bowel obstruction, infertility, abdominopelvic pain, and difficult reoperative procedures [1–3]. In addition, adhesions have a substantial impact on the national health economy. In a current Swedish survey, the annual cost of adhesionrelated problems was estimated to be €39.9–59.5 million, and the cost of inpatient readmissions was almost equal to that for gastric cancer [4]. The peritoneum is the largest serous membrane, with a surface of 2 m2. It covers the visceral organs (visceral peritoneum) and lines the abdominal cavity (parietal peritoneum) [5]. The peritoneum is composed of a monolayer of mesothelial cells of mesenchymal origin, resting on a continuous basement membrane supported by the submesothelium. The submesothelial layer consists of the extracellular matrix made up of different types of collagen, glycoproteins, glycosaminoglycans, and proteoglycans [5]. Diffusion and resorption of fluid occur freely through the mesothelium and submesothelial stroma. The luminal surface of mesothelial cells has numerous microvilli, increasing the peritoneal surface area up to 40 m2 for exchange between mesothelial cells and the peritoneal cavity. Overall, the peritoneum must be regarded as an organ that has a protective function for the contents of the abdominal cavity. Peritoneal defects during surgical procedures result in a reduced supply of oxygen and nutrients as well as an impaired ability to remove metabolic byproducts [6]. Correspondingly, it has been suggested that adhesions may act as vascular grafts between healthy organs and areas of ischemic tissue, reflecting the body’s attempt to overcome local damage [7]. It is generally supposed that peritoneal adhesions reflect a kind of modified regeneration of the peritoneal surface, initially as tender and fibrinous bands that are transformed to inert scar tissue with fibroblasts and collagen bundles [1]. In accordance with Epstein et al. [8], we found human peritoneal adhesions to be highly cellular,

well-vascularized proliferating tissue, indicating a dynamic and persistent remodeling [8, 9]. Besides plasmin, plasminogen activator, and plasminogen activator inhibitor, other factors–including transforming growth factor beta, matrix metalloproteinases, tissue inhibitors of metalloproteinases, insulin-like growth factor 1, and platelet-derived growth factor–have been revealed to be important mediators involved in peritoneal healing, all interacting with each other (⊡ Fig. 42.1) [10]. Currently, the impact of inflammatory stimulants–including chemoattractants [interleukin (IL)-8, monocyte chemotactic protein-1] and cytokines (tumor necrosis factor alpha, IL-1β, IL-6)–as products of invaded polymorphonuclear granulocytes, monocytes, and leucocytes is increasingly discussed as an important factor in adhesiogenesis [1–13]. The aim of the first study was to investigate whether human peritoneal adhesions reveal inflammatory activity and whether persistent adhesions reflect a disturbed peritoneal cell differentiation, proliferation, and migration. To test this hypothesis, we focused on the appearance of macrophages (CD68), B-lymphocytes (CD20), and T-lymphocytes (CD45) as main representatives of the cellular immune response. Furthermore, we measured the occurrence of cyclooxygenase-2 (COX-2) as a pivotal component of inflammatory cell activity. Finally, we analyzed the expression profiles of Notch-3, ß-catenin, and c-myc as important mediators of cell differentiation, proliferation, and migration involved in wound healing. The aim of the second study was to investigate the kinetics of peritoneal adhesions in a rat model with special regard to the cellular immune response [T-lymphocytes (CD3) and macrophages (CD68)], inflammatory cell activity (COX-2), and cell differentiation, proliferation, and migration (ß-catenin and c-myc).

Patients and Methods Study I: Patient Information Adhesions were prospectively collected from 40 patients undergoing laparotomy at the surgical

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⊡ Fig. 42.1. Elementary steps and complementary factors involved in the adhesion formation process according to Duron [10] (PA plasminogen activator; PAI plasminogen activator inhibitor; TGF transforming growth factor; FSP fibrin split products; MMP matrix metalloproteinase; ECM extracellular matrix)

department of the RWTH Aachen University Hospital, Germany. The study was approved by the local ethics committee, and patients gave written informed consent to participate in the trial. The clinical parameters acquired included age, gender, diagnosis, and surgical and medical history. Adhesion maturity was calculated from the date of the last previous abdominal surgery, according to Herrick et al. [14]. In each patient, one sample of 5–10 mm was excised from the visceral peritoneum close to the intestine, and another sample of 5–10 mm was excised from the parietal peritoneum distant from the peritoneum. Tissue specimens were immediately fixed in 4% paraformaldehyde and embedded in paraffin wax.

Study II: Animal Model and Surgical Procedure The animal experiment was approved by the Animal Care and Use Review Committee of the Russian State Medical University, Moscow. All animals were housed in accordance with the requirements of the German Animal Protection Act. For the experiment, 60 male Sprague–Dawley rats with a mean body weight of 380 g were used. All animals were kept under standardized conditions: temperature 22–24°C, relative humidity 50–60%, and 12 h of light following 12 h of darkness. The animals had free access to food and water. Food was withdrawn 12 h before and after surgery. All operations were carried out under general anesthe-

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sia and aseptic and sterile surgical conditions. The surgical procedure (explantation of the adhesion tissue) was done at the Joint Institute for Surgical Research of the Russian State Medical University in Moscow. After introduction by isoflurane, general anesthesia was achieved with a subcutaneous mixture of 0.3 mg/kg medetomidine and 100 mg/kg ketamine hydrochloride. The rats were weighed, and their skin was shaved and disinfected with a polyvidone–iodine solution. The animals were fixed in a supine position. Laparotomy was performed by a 4-cm midline incision, and then a standardized peritoneal defect with a diameter of 2 cm at the cecal area was created. The abdominal wall and skin were separately closed with continuous absorbable 4/0 polyglactin sutures (Vicryl). No additional antibiotic treatment was given before or during the experimental setting. On postoperative days 3, 5, 14, 30, 60, and 90, 10 animals, respectively, were sacrificed and weighed for morphological, histological, and immunohistochemical observations. In each animal the developed adhesion tissue, including parietal and visceral peritoneum, was explanted, and tissue specimens were immediately fixed in 4% paraformaldehyde and embedded in paraffin wax.

Histological Assessment Histological and immunohistochemical investigations were done at the Surgical Department of the RWTH Aachen University Hospital, Germany, and were performed on paraffin-embedded 3-μm sections using peroxidase-conjugated, affinity-isolated immunoglobulins. All sections were routinely stained with hematoxylin and eosin (H&E) and were processed at the same time to reduce internal staining variations. Briefly, immunohistochemistry was done subject to the avidin–biotin complex method and according to the manufacturer’s instructions. Macrophages (CD68) were identified by a 1:50 mouse monoclonal antibody from Dako (Glostrup, Denmark), with microwave pretreatment three times, citrate buffer pH 6, and rabbit antimouse 1:300 (Dako) as secondary antibody. For the detection of B-lymphocytes (CD20) and T-lymphocytes (CD45, CD3), we used a mouse monoclonal pri-

mary antibody 1:100 (Dako), and as secondary antibody we used rabbit antimouse 1:300 (Dako). Cyclooxygenase-2 (COX-2) detection was carried out by a 1:100 rabbit monoclonal antibody from DCS (Hamburg, Germany), with microwave pretreatment three times, citrate buffer pH 6, and goat antirabbit 1:300 (Dako) as secondary antibody. For Notch-3 staining, we used a 1:50 rabbit polyclonal antibody from Santa Cruz Biotechnology (Santa Cruz, CA, USA), with microwave pretreatment three times, citrate buffer pH 6, and goat antirabbit 1:500 (Dako) as secondary antibody. Beta-catenin was analyzed by a ready-to-use rabbit polyclonal antibody from Spring Bioscience (Pleasanton, CA, USA) and goat antirabbit 1:500 (Dako) as secondary antibody. Furthermore, c-myc expression was investigated by a 1:50 rabbit polyclonal antibody (Santa Cruz Biotechnology) and goat antirabbit 1:500 (Dako) as secondary antibody. The expression of immunohistochemical parameters was classified by two independent, blinded observers using a semiquantitative immunoreactivity score according to the method of Remmele and Stegner [15]. Intensity of staining was scored as 0 (negative), 1 (weak), 2 (medium), or 3 (intensive). The extent of staining was scored as 0 (0%), 1 (1–20%), 2 (21–50%), 3 (51–80%), or 4 (81–100%), indicating the percentage of positive staining in adhesion tissue. Multiplication of the intensity score (0–3) and the extent score (0–4) resulted in the immunoreactivity score, ranging between 0 and 12. Sections were examined by standard light microscopy (Olympus BX51, Hamburg, Germany). For each sample, six regions (×400, area 100×100 μm) were captured by a digital camera (Olympus C-3030, Hamburg, Germany).

Results Study I: Human Peritoneal Adhesion Tissue The mean patient age was 55±19 years, and 17 female and 23 male patients were included in the study. Eighteen of the 40 patients had had one previous abdominal operation, and 22 patients had had two or more. The parameters measured were

309 Chapter 42 · Adhesion as a Chronic Inflammatory Problem? Risk for Adhesions, Migration

a

b

c

d

42

⊡ Fig. 42.2. Immunohistochemical features of peritoneal adhesion specimens demonstrating specific nuclear staining for Tlymphocytes (CD45) and macrophages (CD68). T-lymphocytes were evident in peritoneal adhesions younger than 12 months (a) and even in adhesions older than 12 months (b) without significant differences. Views c and d illustrate the specific nuclear staining of macrophages (CD68), with significantly higher expression in adhesions <12 months (c) compared with adhesions >12 months (d). (Magnification ×400)

not significantly affected by the gender or age of the patients or by the number of previous operations.

T-lymphocytes (CD45) and Macrophages (CD68) Investigation of the H&E-stained sections revealed extended infiltrates of mononuclear round cells. Subtyping of these cells by CD68 and CD45 displayed predominant macrophages and T-lymphocytes. They were colocalized within the entire specimen, and the appearance of these cells correlated significantly with each other (r=0.624, p<0.001). Adhesions with an age <12 months showed a significantly elevated expression level of CD68 (mac-

rophages) compared with adhesions >12 months (p<0.05). The expression of CD45 revealed no significant differences regarding adhesion maturity (p>0.05). (See ⊡ Fig. 42.2.)

Analysis of COX-2, ß-catenin, c-myc, and Notch-3 COX-2 showed a positive cytoplasmic staining with a mean score of 3±2.4. Similarly, ß-catenin was expressed in the cytoplasm of endothelial cells of blood vessels and fibroblasts (mean score 3.5±1.9). C-myc (mean score 3.1±1.8) showed positive nuclear staining, both in mononuclear round cells and in fibroblasts predominantly surrounding

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a

b

c

d

e

f

⊡ Fig. 42.3. Immunohistochemical features representing protein expression levels in peritoneal adhesions. Expression of Notch-3 (a), ß-catenin (b), and c-myc (c) in adhesions <12 months. Expression of Notch-3 (d), ß-catenin (e), and c-myc (f) in peritoneal adhesions >12 months. (Magnification ×400)

a

b

⊡ Fig. 42.4. Percentage of CD3-positive-stained cells representing a continuous infiltration of macrophages in visceral (a) and parietal (b) peritoneal adhesions

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a

42

b

⊡ Fig. 42.5. a Percentage of CD68-positive-stained cells demonstrating a significantly higher expression in visceral adhesions on postoperative days 3 and 5. b A significantly higher infiltration of macrophages was measured in parietal adhesions on postoperative days 60 and 90

blood vessels. Expression of Notch-3 (mean score 6.3±3.4) was pronounced in all specimens. Positive staining was detected in the nucleus as well as in the cytoplasm of both mononuclear round cells and fibroblasts (⊡ Fig. 42.3).

Study II: Experimental Data During the observation period, none of the rats died or exhibited signs of infection. All rats developed peritoneal adhesions.

T-lymphocytes (CD3) and Macrophages (CD68) Both at the parietal and the visceral sites of the adhesions, T-lymphocytes could be detected. The expression profile of CD3 was stable even until the 90th postoperative day. Neither over the course of time nor when comparing the parietal to the visceral site were significant differences seen regarding the expression of CD3 (⊡ Fig. 42.4). Likewise, macrophages were detectable until the 90th postoperative day. At postoperative days 3 and 5, the infiltration of macrophages was significantly elevated at the visceral site of the adhesions compared

with the parietal site. At postoperative days 60 and 90, significantly more macrophages were detectable in parietal adhesions compared with visceral adhesions (⊡ Fig. 42.5).

Cyclooxygenase-2, ß-catenin, and c-myc A significant expression of COX-2 was evident in all adhesions, both at the parietal and visceral sites of the adhesions even 90 days after the operation. Over the course of time, COX-2 was significantly reduced from the 3rd to the 90th postoperative days. The expression of COX-2 at the visceral site of the adhesions was significantly higher on postoperative days 3, 5, and 14 compared with the parietal adhesion sites. The expression of COX-2 was significantly elevated at the parietal site of the adhesions on postoperative days 30, 60, and 90 compared with the visceral site (⊡ Fig. 42.6). Both ß-catenin and c-myc were detected at the visceral site of the adhesions. Over time, the expression profile of both parameters showed no significant differences even 90 days following the operative procedure (⊡ Fig. 42.7). At the parietal site of the adhesions, ß-catenin was evident without significant differences over the course of time. However, c-myc was not detectable at the parietal site (⊡ Fig. 42.7).

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a

b

⊡ Fig. 42.6. Collectively, there was a continuously marked expression of COX-2 until the 90th postoperative day. a In visceral adhesions, the expression was significantly higher on postoperative day 3, 5, and 14. b A significantly higher expression was measured in parietal adhesions on postoperative days 30, 60, and 90

a

b

⊡ Fig. 42.7. a Persistent expression of ß-catenin and its target c-myc in visceral adhesions. b A persistent expression of ß-catenin was detected in parietal adhesions, although no expression of c-myc was found distant to the intestine

Discussion Traumatic peritoneal defects are presumed to initiate adhesion formation, whereas the causation of maintaining peritoneal adhesions has not been previously revealed [16–19]. Analogous to physi-

ological wound healing and with lack of infection, a time-dependent termination of the inflammatory activity and a transformation of transient peritoneal adhesions into scar tissue has been suspected [20, 21]. Analysis of human peritoneal adhesions demonstrated that they were cell-rich, well-vascu-

313 Chapter 42 · Adhesion as a Chronic Inflammatory Problem? Risk for Adhesions, Migration

larized, and innervated tissue. In a previous study we also found them to be high in adipose tissue, fibroblasts, and mononuclear round cells such as macrophages and T-lymphocytes, irrespective of the adhesions’ maturity [3]. In 2007 Hoshino et al. demonstrated that peritoneal macrophages trigger the development of peritoneal adhesions via the chemokine receptor 8 (CCR8) and its target, the chemokine ligand 1 (CCL1) [22]. Concordantly, we detected macrophages in long-lasting peritoneal adhesions both in a rat model and even in mature human peritoneal adhesions. The evidence of a significantly higher infiltration of macrophages in the early postoperative period supports the assumption that macrophages trigger the development of peritoneal adhesions. In quantity and quality, T-lymphocytes were found to have no significant differences regarding adhesion maturity. Consequently, an ongoing persistent inflammatory process with a functional impact of T-lymphocytes or T-lymphocytesynthesized chemokines in maintaining peritoneal adhesion may be suspected. Cyclooxygenase-2 (COX-2) is a regulatory factor in the biosynthesis of prostanoids such as prostaglandins, prostacyclin, and thromboxanes [23–25]. COX-2 expression is induced by a variety of growth factors and cytokines, and the expression increases rapidly in response to inflammatory stimuli and tissue damage [26–30]. During physiological wound healing, expression of COX-2 regularizes within weeks after injury [31]. Saed et al. measured significantly higher levels of COX-2 in vitro in adhesion fibroblasts compared with normal peritoneal fibroblasts and assumed an altered cell regulation in peritoneal wound healing [30]. In accordance with these findings, we detected an expression of COX-2 in human peritoneal adhesions that was irrespective of adhesion maturity. Although a continuous decrease in COX-2 expression was measured over the course of time in our rat model of adhesion formation, a substantial expression was evident even 90 days following the surgical trauma. The consideration of adhesions as widely areactive fibrotic bands has been challenged; actually, adhesion formation may be regarded as a defective wound healing process and as a disturbed

42

in situ regeneration of the peritoneal surface [32]. Notch-3, ß-catenin, and c-myc are well-known mediators in cell signaling pathways of proliferation and differentiation responses during normal development and wound healing [33, 34]. Notch proteins are single-pass transmembrane receptors, playing a critical role in control and cell-fate decisions during developmental processes [35]. Notch favors cell proliferation and opposing cell differentiation and is closely connected to Wnt signaling. ß-catenin and its target c-myc are crucial mediators of Wnt signaling and are thereby involved in the regulation of cell growth, cell differentiation, and tissue remodeling [36–39]. Activation of the ß-catenin/c-myc pathway contributes to impaired healing by inhibiting cell migration and altering cell differentiation [40]. In accordance, a marked expression of Notch-3, ß-catenin, and c-myc could be verified even in mature human peritoneal adhesions, indicating disturbed differentiation, migration, and proliferation of mesothelial cells. Likewise, ß-catenin and c-myc were detected in the rat model of adhesion formation, confirming the assumption of a disturbance in peritoneal wound healing. In conclusion, peritoneal adhesions should be regarded as a consequence of continuously malfunctioning cell differentiation and proliferation within a chronic inflammatory process. It remains unclear whether the chronic inflammatory process or the malfunctioning differentiation/proliferation is causative in adhesiogenesis. Influencing the individual inflammatory response to peritoneal trauma seems to be necessary to avoid or at least reduce the formation of postoperative peritoneal adhesions.

References 1. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management. Dig Surg 2001;18(4):260–73 2. Menzies D, Ellis H. Intestinal obstruction from adhesions–how big is the problem? Ann R Coll Surg Engl 1990;72(1):60–3 3. Hammoud A, Gago LA, Diamond MP. Adhesions in patients with chronic pelvic pain: a role for adhesiolysis? Fertil Steril 2004;82(6):1483–91

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4. Tingstedt B, Isaksson J, Andersson R. Long-term follow-up and cost analysis following surgery for small bowel obstruction caused by intra-abdominal adhesions. Br J Surg 2007;94(6):743–8 5. van der Wal JB, Jeekel J. Biology of the peritoneum in normal homeostasis and after surgical trauma. Colorectal Dis 2007;9 Suppl 2:9–13 6. Diamond MP, El-Hammady E, Munkarah A, Bieber EJ, Saed G. Modulation of the expression of vascular endothelial growth factor in human fibroblasts. Fertil Steril 2005;83(2):405–9 7. Ellis H. The aetiology of post-operative abdominal adhesions. An experimental study. Br J Surg 1962;50:10–16 8. Epstein JC, Wilson MS, Wilkosz S, Ireland G, O’Dwyer ST, Herrick SE. Human peritoneal adhesions show evidence of tissue remodeling and markers of angiogenesis. Dis Colon Rectum 2006;49(12):1885–92 9. Binnebosel M, Klinge U, Rosch R, Junge K, Lynen-Jansen P, Schumpelick V. Morphology, quality, and composition in mature human peritoneal adhesions. Langenbecks Arch Surg 2007; 393(1):59–66 10. Duron JJ. Postoperative intraperitoneal adhesion pathophysiology. Colorectal Dis 2007;9 Suppl 2:14–24 11. Cahill RA, Wang JH, Redmond HP. Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation. Surgery 2007;141(3):403–10 12. Ito T, Fraser IP, Yeo Y, Highley CB, Bellas E, Kohane DS. Antiinflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone. Biomaterials 2007;28(10):1778–86 13. Cook AD, Vlahos R, Massa CM, Braine EL, Lenzo JC, Turner AL, Way KJ, Hamilton JA. The effect of tissue type-plasminogen activator deletion and associated fibrin(ogen) deposition on macrophage localization in peritoneal inflammation. Thromb Haemost 2006;95(4):659–67 14. Herrick SE, Mutsaers SE, Ozua P, Sulaiman H, Omer A, Boulos P, Foster ML, Laurent GJ. Human peritoneal adhesions are highly cellular, innervated, and vascularized. J Pathol 2000;192(1):67–72 15. Remmele W, Stegner HE. [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe 1987;8(3):138–40 16. Alpay Z, Ozgonenel MS, Savasan S, Buck S, Saed GM, Diamond MP. Possible role of natural immune response against altered fibroblasts in the development of post-operative adhesions. Am J Reprod Immunol 2006;55(6):420–7 17. Roy S, Clark CJ, Mohebali K, Bhatt U, Wallace WA, Nahman NS, Ellison EC, Melvin WS, Sen CK. Reactive oxygen species and EGR-1 gene expression in surgical postoperative peritoneal adhesions. World J Surg 2004;28(3):316–20 18. Whawell SA, Scott-Coombes DM, Vipond MN, Tebbutt SJ, Thompson JN. Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells. Br J Surg 1994;81(2):214–6

19. Whawell SA, Vipond MN, Scott-Coombes DM, Thompson JN. Plasminogen activator inhibitor 2 reduces peritoneal fibrinolytic activity in inflammation. Br J Surg 1993;80(1):107–9 20. Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, McGuire A, Lower AM, Hawthorn RJ, O’Brien F, Buchan S, Crowe AM. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet 1999;353(9163):1476–80 21. Jirasek JE, Henzl MR, Uher J. Periovarian peritoneal adhesions in women with endometriosis. Structural patterns. J Reprod Med 1998;43(3 Suppl):276–80 22. Hoshino A, Kawamura YI, Yasuhara M, Toyama-Sorimachi N, Yamamoto K, Matsukawa A, Lira SA, Dohi T. Inhibition of CCL1-CCR8 interaction prevents aggregation of macrophages and development of peritoneal adhesions. J Immunol 2007;178(8):5296–304 23. Minghetti L, Polazzi E, Nicolini A, Creminon C, Levi G. Up-regulation of cyclooxygenase-2 expression in cultured microglia by prostaglandin E2, cyclic AMP and non-steroidal anti-inflammatory drugs. Eur J Neurosci 1997;9(5):934–40 24. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107(4):1183–8 25. DuBois RN, Tsujii M, Bishop P, Awad JA, Makita K, Lanahan A. Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells. Am J Physiol 1994;266(5 Pt 1):G822–G827 26. Siegler AM, Kontopoulos V, Wang CF. Prevention of postoperative adhesions in rabbits with ibuprofen, a nonsteroidal anti-inflammatory agent. Fertil Steril 1980;34(1):46–9 27. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107(4):1183–8 28. Cofer KF, Himebaugh KS, Gauvin JM, Hurd WW. Inhibition of adhesion reformation in the rabbit model by meclofenamate: an inhibitor of both prostaglandin and leukotriene production. Fertil Steril 1994;62(6):1262–5 29. Rodgers KE, Girgis W, Campeau JD, diZerega GS. Reduction of adhesion formation by intraperitoneal administration of anti-inflammatory peptide 2. J Invest Surg 1997;10(1-2):31–6 30. Saed GM, Munkarah AR, bu-Soud HM, Diamond MP. Hypoxia upregulates cyclooxygenase-2 and prostaglandin E(2) levels in human peritoneal fibroblasts. Fertil Steril 2005;83 Suppl 1:1216–9 31. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N. Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab Invest 2002;82(11):1503–13 32. Binnebosel M, Rosch R, Junge K, Lynen-Jansen P, Schumpelick V, Klinge U. Macrophage and T-lymphocyte infiltrates in human peritoneal adhesions indicate a chronic inflammatory disease. World J Surg 2008;32(2):296–304

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33. Hayward SD, Liu J, Fujimuro M. Notch and Wnt signaling: mimicry and manipulation by gamma herpesviruses. Sci STKE 2006;2006(335):re4 34. Rodewald HR. Making a Notch in the lymphocyte kit. Eur J Immunol 2006;36(3):508–11 35. Deregowski V, Gazzerro E, Priest L, Rydziel S, Canalis E. Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling. J Biol Chem 2006;281(10): 6203–10 36. Schneikert J, Behrens J. The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut 2006; 56(3):417–25 37. Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC. Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets 2004;4(8):653–71 38. Dihlmann S, von Knebel DM. Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics. Int J Cancer 2005;113(4):515–24 39. Bhatia N, Spiegelman VS. Activation of Wnt/beta-catenin/ Tcf signaling in mouse skin carcinogenesis. Mol Carcinog 2005;42(4):213–21 40. Stojadinovic O, Brem H, Vouthounis C, Lee B, Fallon J, Stallcup M, Merchant A, Galiano RD, Tomic-Canic M. Molecular pathogenesis of chronic wounds: the role of betacatenin and c-myc in the inhibition of epithelialization and wound healing. Am J Pathol 2005;167(1):59–69

Discussion Franz: Even on the surface of the skin, it is difficult to define what a chronic wound is. One way is to look at the fibroblasts. For example, what about the fibroblast function? Binnebösel: But how should we investigate the function of the fibroblasts? We have not done it. Of course, it is a very important subject, but when we looked at these adhesions there was a small amount of fibroblasts. Franz: So when you said »cell-rich,« you mainly meant inflammatory cells? Binnebösel: Yes Schumpelick: Is the adhesion story a one-way story, or is there a way back to normal tissue? Binnebösel: At the moment, we just do not know. We do not know whether peritoneal adhesions are a reaction of everybody, and we do not know why in some patients adhesions dissolve and in some patients they do not. And we have to find a solution for this problem.

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Smeds: From the clinical point of view, I wonder if you had information about the dynamics of the adhesions and whether there is a correlation to pain. Binnebösel: In our investigation we found no correlation to pain. Interestingly, previous publications showed that the amount of adhesions will increase with the number of previous operations— but this was different in our investigation. At the moment, it seems unpredictable. Smeds: Do you think it is a mechanical traction of the peritoneum and the adhesion that promotes the pain? Binnebösel: Yes, this is a possible explanation for the pain. Montgomery: Where did you get the biopsies? I think it is difficult to get reproductive biopsies? Binnebösel: Yes, this is a limitation of our study, because we randomly took two biopsies in every patient. It is very difficult to define macroscopically where it is best to take the biopsies.

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Biological Tissue Graft: Present Status C. Bellows

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Overview of the Disease

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Reconstruction of abdominal wall defects is a challenging problem that many surgeons face, not only in the elective setting but also during emergency surgery. Deficiencies of the abdominal wall can be acute or chronic in nature and can result from trauma, cancer, infection, or hernia disease. Incisional hernias are the most common cause of a chronic abdominal wall defect. Despite advances in medical technology, treatment of these defects remains controversial. In fact, the repair of abdominal wall defects continues to be imperfect and costly, resulting in serious, chronic healthcare problems. Current practice guidelines and medical evidence support the use of a permanent prosthetic mesh for the repair of hernias as a means to reduce the risk of recurrent hernia. Patients who are not repaired with mesh, either owing to clinical complications or by surgeon choice, have a much higher incidence of recurrent hernia compared with patients who are repaired with mesh [1–3]. Consequently, multiple prosthetic meshes with a variety of characteristics have been developed. However, no single material has gained universal acceptance or preference, and a number of complications have been associated with the use of these permanent synthetic materials [4–8]. Most synthetic mesh strengthens the abdominal wall by inciting an intense fibroplastic response to form a strong scar-plate interface. Although this works well, the inflammatory response incited by the plastic meshes can lead to potentially serious complications such as bowel fistulation, mesh contraction, intraperitoneal adhesions, erosion into the abdominal viscera, a sensation of being able to feel the mesh, and increased stiffness of the abdominal wall with loss of compliance. Additionally, the U.S. Food and Drug Administration has received numerous reports of other complications associated with mesh, including chronic pain and infection [9]. Indeed, mesh infections are one of the most commonly reported complications and represent a potential nightmare. An infection is traumatic for the patient and time-consuming to treat. Bacteria adhere avidly to the mesh polymers and immediately lay down a biofilm, which protects them from host immunological defenses and

antibiotics and thereby ensures their long-term survival and leads to chronic infection of the hernia wound [10]. The increased morbidity and costs associated with infected mesh are so dire that surgeons avoid placing permanent mesh in grossly infected fields. Moreover, surgeons are now avoiding placing permanent mesh in clinical circumstances in which the risk of infection is increased, such as in patients with a prior wound infection. Predictably, strategies to address these complications related to the implantation of synthetic materials are now the focus of intense research by hernia surgeons. An extensive search is ongoing for alternative materials with which to not only achieve tension-free repair of an abdominal wall defect in a single-stage operation (especially in the setting of a contaminated wound) but also to achieve a functional abdominal wall and a better quality of life for the patient after repair. This search has led to an era of acellular biological tissue grafts (e.g., derived from natural materials).

Rationale and Indications for Using Biological Tissue Grafts The art and science of using tissue grafts from animal (xenogenic) and human (allogenic) sources for abdominal wall reconstruction is nascent. However, during the past few years, several biological tissue grafts have been introduced and are available for hernia repair. The rationale for using a biological tissue graft for abdominal wall reconstruction is to avoid acute and chronic mesh infection, unwanted chronic inflammation, and scar tissue formation, which occur frequently in response to permanent synthetic materials after implantation. The potential benefits of these new materials are extremely attractive and include superior biocompatibility (i.e., minimum inflammatory response), reduced adhesion formation, early vascular ingrowth, and decreased risk of infection in contaminated or potentially contaminated surgical fields. From a pathophysiological viewpoint, there are two different indications for biological tissue grafts: One is to repair an acute abdominal wall defect created by trauma, cancer, or infection, and the other is to repair a chronic, progressive ab-

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dominal wall defect (i.e., hernia disease) resulting from a presumed defective collagen metabolism or impaired wound healing (such as in steroid users). Whereas acute wound defects can be repaired with a biological tissue graft as a scaffold to induce normal tissue regeneration, such an approach may lead to an inadequate and weak scar in patients with chronic abdominal wall defects after remodeling is complete. However, as is the case with any new medical device or product introduced into clinical practice, experience and time will ultimately define the utility and limitations.

Types of Biological Tissue Grafts: Distinguishing Features Biological tissue grafts are rendered acellular through various methods of preservation and fabrication and are offered as collagen-rich scaffolding that allows cellular ingrowth and tissue remodeling and revascularization, thereby setting the stage for an intact hernia repair. However, the specific manufacturing processes that yield modified collagen matrices vary significantly from one product to another. Therefore, each product can be classified according to the material source, type of tissue, presence or absence of collagen cross-linking, decellularization methods, and terminal sterilization methods. Currently, the different donor species grafts, including human and animal (porcine, bovine), are made of one of three types of tissue: dermis, small intestine, or pericardium. The various decellularization methods include physical (dissection, agitation, sonication, pressure, freeze–thaw), chemical (detergents, ionic solutions, acid/bases), and enzymatic methods. The various terminal sterilization methods include gamma irradiation, ethylene oxide gas, and hydrogen peroxide plasma. A few materials also employ a chemical cross-linking method in the preservation/processing of their collagen tissue grafts. Experimental studies have demonstrated that collagen cross-linked with glutaraldehyde imparts a high degree of stability to the collagen against the activity of the degrading enzyme, collagenase [11, 12], thereby slowing or stopping the degradation of the donor collagen. However, some investigators

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believe that this chemical cross-linking leads to nonincorporation and preclusion of immune cell penetration, making these grafts unable to participate in normal tissue remodeling. Instead, immune cells encapsulate the grafts, consistent with a foreign body response. Based on the variety of tissue origins as well as distinct processing and sterilization procedures, experimental studies have demonstrated that currently available biological tissue grafts vary in performance characteristics, such as cellular response, strength, biodegradability, susceptibility to infection, and tendency to transmit diseases from donor to recipient after implantation [13]. Therefore, the use of biological tissue grafts for treating hernia disease needs to be considered on a product-byproduct basis as additional knowledge from clinical trials and clinical experience accumulates.

Biological Tissue Grafts: Clinical Data The first biological tissue graft was approved for soft tissue reconstruction in 1999. Since that time, the number of different products and the use of these materials in clinical practice have grown rapidly for want of a better solution for difficult hernia repairs. Currently, over 13 biological tissue grafts are commercially available. However, after many years on the market, some biological graft materials have been the subject of dozens of peerreviewed publications, whereas a number of other products have been reported on in few or no publications–clinical or preclinical–indexed in Medline. For example, a recent Medline search revealed 33 published articles on small intestinal submucosa grafts, 32 on acellular human dermis grafts, and 13 on cross-linked porcine dermis grafts [14]. Interestingly, most of this published experience with biological grafts is in clean field cases rather than in infected fields. Despite some encouraging early results, several clinical complications have been reported following the use of these biological materials to reconstruct abdominal wall defects, including degradation, laxity, lack of integration, and recurrence. Although the companies developing and marketing biological tissue grafts make various claims for

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the superiority of their product over others, as of this writing, there are no prospective, randomized clinical trial data comparing one biological tissue graft to another and no data demonstrating the superiority of one particular biological tissue graft over a synthetic graft. Despite this lack of data, there is growing concern that not all biological tissue grafts perform uniformly after implantation in humans. Clinical data suggest that outcomes may be related in part to the material source and the processing method of these different biological tissue grafts. For example, a recent systematic review reported a failure rate of 8% at 19 months for small intestinal submucosa grafts when used for ventral hernia repair [14]. By comparison, an aggregate failure rate of 15% at 12 months was reported for noncross-linked acellular human dermis grafts and 8% at 15 months for cross-linked porcine dermis [14]. These results may also be related to the implant scenarios, the implantation technique, a relatively short duration of follow-up for many of these studies, and underreporting of complications related to the use of these products. For example, it is well documented that using biological tissue grafts in infected fields results in significantly higher failure rates than when they are implanted in clean fields. Not only do these patients tend to be more emergent or critically ill, but patients with infected fields also present the additional factor of material digestion by bacterial enzymes that may weaken a biological graft. Importantly, there have been more reports on acellular human dermis grafts used in infected fields compared with small intestinal submucosa grafts [14]. The techniques used are also very important in hernia repair outcomes, and implantation techniques appear to be especially important with biological grafts. Currently, several publications have reported on the use of acellular human dermal matrix in hernia repair, suggesting that recurrences are highest (80%) when the product is used as a fascial bridge to repair the defect [15]. By comparison, when the same biological tissue graft is used to reinforce a primary reapproximation of the fascia, utilizing the component separation technique, recurrence rates as low as 0–5% have been reported at 2-year follow-up [16]. Taken together,

these data suggest that the use of biological tissue grafts may not be justified unless primary wound closure can be achieved.

Summary and Conclusions Abdominal wall integrity may be lost after trauma, infection, herniation, or surgical resection. The surgical repair of these abdominal wall defects has changed considerably over the last decades. Currently, a wide variety of new implantable acellular biological tissue grafts have been developed and introduced into the clinical market for the repair of tissue defects. The sudden and rapid emergence of these grafts has provided surgeons with an important new tool in their surgical armentarium for treating abdominal wall defects, especially in contaminated or infected surgical fields. When the complexity of the patients and the implant scenarios is taken into consideration, biological grafts have demonstrated a good overall success rate. However, at present the data from prospective trials and case series are limited, with mostly short-term follow-up of patients treated with biological tissue grafts for abdominal wall reconstruction. More clinical work is necessary to determine which patients would benefit the most from repair using a biological tissue graft. To date, the best clinical outcomes reported with biological tissue grafts for abdominal wall reconstruction occur in patients in the absence of gross infection and when the graft is used as a fascial reinforcement. However, these first-generation biological tissue grafts are far from ideal. The ideal biological tissue graft may take one of a number of possible forms in the near future. The most economical and proficient graft would be one derived from a plentiful source, thus making it affordable. In addition, the ideal graft material should have an adequate shelf life so that it can be taken off the shelf and used immediately; it should be 100% biocompatible; and it should resist infection. Degradation and replacement of the graft material by host tissue should ultimately occur in a manner that maintains or increases the strength of the abdominal wall repair. It may also be hypothesized that the composition of an ideal biological

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tissue graft is able to restore normal wound healing in hernia formers and thereby strengthens the resulting scar. No biological tissue graft has yet been shown to possess all of these ideal characteristics. There is increasing evidence that biological tissue grafts will become more customized or individually tailored for specific needs. An animal can have its own tissues (such as myofibroblasts or stem cells) harvested and seeded onto extracellular matrices prior to being transplanted back into its body. This approach primes or preconditions the biological tissue graft with the intended recipient animal’s own progenitor cells. Such an approach could add to the overall effectiveness of a biological tissue graft, making it more resistant to bacterial colonization and accelerating the deposition of collagen, which may more rapidly increase the strength profile [17]. Strategies to accelerate neovascularization of transplanted biological tissue grafts after implantation will facilitate their engraftment through the early delivery of oxygen, nutrients, host immune cells, and antibiotics. The preseeding of stem cells or progenitor cells into tissue grafts could also offer an advantage with respect to the need for rapid revascularization, as these cells are resistant to low oxygen conditions. All of these approaches to create a »designer extracellular matrix« are within reach in the near future. Perhaps such an approach will be called »smart biological tissue grafts.«

References 1. Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–398 (2000) 2. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J. Long term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 4:578–585 (2004) 3. Sanchez LJ, Bencini L, Moretti R. Recurrence after laparoscopic ventral hernia repair: results and critical review. Hernia 8:138–143 (2004) 4. Carbonell AM, Harold KL, Mahmutovic AJ et al. Local injection for the treatment of suture site pain after laparoscopic ventral hernia repair. Am Surg 69:688–691 (2003) 5. Leber GE, Garb JL, Alexander AI, Reed WP. Long term complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378–382 (1998)

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6. Morris-Stiff GJ, Hughes LE. The outcomes of nonabsorbable mesh placed within the abdominal cavity: literature review and clinical experience. J Am Coll Surg 186:352– 367 (1998) 7. Welty G, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick V. Functional impairment and complaints following incisional hernia repair with different polypropylene meshes. Hernia 5:142–147 (2001) 8. Klinge U, Klosterhalfen B, Birkenhauer V, Junge K, Conze J, Schumelick V. Impact of polymer size on interface scar formation in a rat model. J Surg Res 103:208–214 (2002) 9. Robinson TN, Clarke JH, Schoen J, Walsh MD. Major mesh related complication following hernia repair: events reported to the Food and Drug Administration. Surg Endosc 19:1556–1566 (2005) 10. Jansen B, Schumacher-Perdreau F, Peters G, Pulverer G. New aspects in the pathogenesis and prevention of polymer-associated foreign-body infections caused by coagulase-negative staphylococci. J Invest Surg 2:361– 380 (1989) 11. Oliver RF, Grant RA, Cox RW, Hulme MJ, Mudie A. Histological studies of subcutaneous and peritoneal implants of trypsin prepared dermal collagen allografts in rats. Clin Orthop 115:291–302(1976) 12. Oliver RF, Barker H, Cooke A, Grant RA. Dermal collagen implants. Biomaterials 23:38–40 (1982) 13. Sandor M, Xu H, Connor J, Lombardi J, Harper JR, Silverman RP, McQuillan DJ. Host response to implanted porcine-derived biologic materials in a primate model of abdominal wall repair. Tissue Eng Part A 14:2021–231 (2008) 14. Hiles M, Record Ritchie RD, Altizer AM. Are biologic grafts effective for hernia repair? A systematic review of the literature. Surg Innov 16:26–37 (2009) 15. Jin J, Rosen MJ, Blatnik J, McGee MF, Williams CP, Marks J, Ponsky J. Use of acellular dermal matrix for complicated ventral hernia repair: does technique affect outcomes? J Am Coll Surg 205:654–660 (2007) 16. Espinosa-de-los-Monteros A, de la Torre JI, Marrero I, Andrades P, Davis MR, Vásconez LO. Utilization of human cadaveric acellular dermis for abdominal wall reconstruction. Ann Plast Surg 58:264–267 (2007) 17. Lai JY, Chang PY, JN Lin. Body wall repair using small intestinal submucosa seeded with cells. J Pediatr Surg 38:1752–1755 (2003)

Discussion Read: This is an excellent paper. We need more of

these, and I think your suggestions are excellent. Falagas: I was impressed by the fact that there

are 13 FDA-approved biological grafts. If it were a medication or drug, the FDA would need two randomized controlled trials with about 1,000 pa-

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tients to show the usefulness of the new product. But for a biological graft—how does the FDA approve them? There were no randomized controlled trials? Bellows: It takes a couple of animal experiments to show that the material is safe, not carcinogenetic….Alloderm gets away with it because it is a minimally processed tissue. But there are some companies now that are taking proactive stents, and actually they are doing prospective randomized trials, comparing the biologics to the synthetics in humans—but they are also selling the products at the same time. Falagas: Would you like to see comparisons of these materials before approval, or are you okay with a few animal experiments? Bellows: Of course not. If the companies do not have any data, I do not use such materials. Ma: Two years ago in Suvretta I presented data about biological meshes in inguinal hernia repair. But afterwards I realized two problems: First, can we use biological meshes if the patient has a collagen deficiency or a family history or a recurrent hernia? Second: What about the bowels, e.g., patients with FAP? Bellows: To your first question, yes, that is something that we need to know—whether these meshes are indicated in patients with collagen disorders. We do not have enough data. The inguinal hernia stuff is a small number of patients. Second, I think it is an indication for a biologic tissue graft. It is an individual decision for each patient, taking into account whether there might be a contamination or reoperation. Again, we do not have all the answers. That is why we need prospective trials with comparisons of the different materials. Kukleta: Among those first 250 reports to the FDA about adverse effects of artificial materials, there are quite a few on SIS. The first paper, as I remember, of 46 cases implanted in humans led to such chaos that they went back to the manufacturer and asked what was wrong with it and if it is really true that it can be used in humans. And now, all of a sudden, everybody thinks that things are getting better. Do you have any explanation? Bellows: I know Surgisis had a lot of problems, as you mentioned. And they went back to the drawing board and performed different types since the

first introduction of the material in the early ’90s. Actually, there is an FDA Web site where voluntarily reported complications with these biological tissue grafts are recorded in a database. And the number one graft that has the most reported complications was actually Permacol. Schumpelick: There was a big difference with regard to laparoscopic or open surgery. Is it because the abdomen is a black box and we do not see the results, or is it because of different milieus? Bellows: I do not think we have the answer yet. Most people are not using these products laparoscopically. Often the data is very rare and the follow-up is very short, so I cannot make any conclusions on this subject.

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IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis D. Berger, M. Bientzle

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Chapter 44 · IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis

Introduction

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Incisional hernias frequently occur after major abdominal surgery [1, 2]. Today the repair should be based on mesh augmentation of the abdominal wall because suturing alone has proved to be ineffective [3–5]. Conventional techniques mainly use meshes in an onlay or sublay position and sometimes intraperitoneally. The laparoscopic approach is characterized by the intraperitoneal placement of meshes and therefore requires a special kind of mesh material. These meshes should provide strong incorporation on one side and prevent adhesions to visceral organs on the other side. One approach is the use of a material that allows the production of a foil with a smooth and a rough surface, such as expanded polytetrafluoroethylene (ePTFE), which was used in most cases of laparoscopic ventral hernia repair reported in the literature [6]. Another possibility is to cover a mesh made of polyester or polypropylene with a resorbable film that prevents adhesions [7, 8]. A third approach is represented by DynaMesh IPOM, which is made of polyvinylidene fluoride (PVDF) containing polypropylene on the parietal side. An inert material such as PVDF, which does not induce adhesions to visceral organs, can be applied as a real mesh structure, with large pores being a precondition of strong and rapid incorporation. The incorporation characteristics can be improved by adding a small amount of polypropylene on the parietal side [9, 10]. This prospective study included 297 consecutive patients with incisional hernias and 47 patients with parastomal hernias treated laparoscopically. The primary targets were the evaluation of the recurrence rate and mesh-related complications.

Patients, Materials, and Methods Patients Between May 2004 and January 2008, 297 unselected patients with incisional hernias and 47 patients with parastomal hernias were prospectively treated and followed. The demographic data are summarized in ⊡ Tables 44.1 and 44.2. The patients

⊡ Table 44.1. Demographic and surgical data of patients with incisional hernias       

Median age: 65 years (22–92) Median body mass index: 29 (17–58) Median hernia size: 122.5 cm2 (2–420) Median mesh size: 600 cm2 (80–2,115) Median operating time: 77.5 min (30–230) Median hospital stay: 8 days (2–36) Median follow-up: 24 months (6–48 in 251/297=84%)

⊡ Table 44.2. Demographic and surgical data of patients with parastomal hernias       

Median age: 69 years (54–92) Median body mass index: 28 (18–57) Median hernia size: 155 cm2 (12–400) Median mesh size: 825 cm2 (525–1,425) Median operating time: 115 min (65–230) Median hospital stay: 10 days (6–66) Median follow-up: 20 months (6–48 in 43/47=91%)

were clinically examined after 1, 3, 6, and 12 months and yearly thereafter.

Surgical Technique Patients were always treated in the supine position. The pneumoperitoneum was established with a Veress needle in cases with an untouched upper quadrant. In all other cases, an open approach was preferred. Usually, three trocars in one flank and one trocar on the opposite side were introduced. Adhesiolysis was performed by sharp dissection without any energy-driven device. Bleeding control was achieved by bipolar coagulation. Routinely, the whole original incision was covered by the mesh. In patients with upper midline incisions, the falciform ligament was dissected, and the space of Retzius was opened as well in cases with lower midline incisions. The mesh was fixed with six stay sutures at the corners and in the midline between the corners in the longest extension. Furthermore, spiral tacks (Protack; Covidien, Mansfield, MA, USA) were used every 3–4 cm. The overlap of the defect and the whole original incision was at least 5 cm.

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The parastomal hernias were repaired by the recently described sandwich technique [11]. After complete adhesiolysis of the whole abdominal wall as described above, a 15×15-cm mesh was incised in a keyhole fashion and placed around the stoma. The mesh incision was closed by transfascial sutures and tacks. A further mesh covering the midline incision and the stoma loop was also used. The stoma loop was finally placed between the two meshes and lateralized for at least 5 cm. A single dose of cefuroxime and metronidazole was generally given prophylactically. DynaMesh IPOM was used in all patients. It represents a real mesh structure that is warpknitted from polyvinylidene fluoride. It contains a small amount of polypropylene on the parietal side, providing good incorporation.

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⊡ Table 44.3. Clinical outcomes of laparoscopic repair of incisional hernias        

   

Recurrences: 1/297 (0.3%) Trocar hernia: 1 (0.3%) Conversion: 1 (0.3%) Bladder laceration treated by Foley catheter: 1 Relaparotomy due to bleeding: 1 Bowel fistula that healed after local revision and vacuum-assisted closure therapy: 1 Punctures due to seroma: 4, with 1 infection due to the puncture Further revisions with resection of the hernia sac because of persistent seroma or hematoma: 3, with 1 postoperative wound infection and 1 patient with intraoperative enterotomy leading to mesh explantation and recurrence Delayed defecation: 5 patients Local revision of a stay suture: 1 Strong pain and additional medical treatment over 3 months: 6 patients Patient deaths: 1 due to pulmonary embolism

Results Incisional Hernia

⊡ Table 44.4. Clinical outcomes of laparoscopic repair of parastomal hernias

⊡ Table 44.1 demonstrates the demographic data, and ⊡ Table 44.3 summarizes the main surgical re-

 Recurrence: 1/47 (2%)  Revisions because of stenosis of the stoma: 2, with a consecutive wound infection in 1 patient  Local revision because of abscess in the hernia sac after puncture of a seroma: 1  Conversion: 1 (2%)  Strong pain and delayed relief: 1 patient, but no redo necessary because of pain  No enterotomy  No bleeding  No further delayed defecation  No deaths

sults. Twenty-three percent (n=67) of our patients with an incisional hernia had undergone previous repairs. Two patients developed a recurrence (0.6%). One recurrence occurred after explantation of the mesh. During surgical excision of the hernia sac, because a persistent seroma caused pain, the mesh was incised and the small bowel opened. A formal laparotomy was necessary to repair the bowel injury, and the mesh was removed. Another patient developed a hernia at the lower border of the mesh, which was originally implanted because of a hernia after an upper midline incision. The new defect was located in the midline between the umbilicus and the symphysis, despite a 5-cm overlap of the lower end of the scar. A persistent seroma was observed in seven patients (2.1%) who had in common a small fascial gap and a major hernia sac. Three of these seven patients experienced major complications after puncture or surgical removal of the sac: two infections and one mesh explantation. However, all patients with a deep wound infection as well as the patient

with an unrecognized enterotomy had a complete recovery without persistent mesh infection. The only bladder injury healed after prolonged transurethral drainage. One patient died on the 7th postoperative day because of pulmonary embolism.

Parastomal Hernia Demographic data are given in ⊡ Table 44.2, and the surgical results are shown in ⊡ Table 44.4. It should be pointed out that 26% of the patients with

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a parastomal hernia were primarily admitted with a recurrent hernia. Only one patient (2%) developed a recurrent hernia. One conversion was necessary because no free abdominal cavity existed, and the pneumoperitoneum could not be established. The main problem, however, is the possibility of producing a stenosis of the stoma loop, which occurred in two patients. In both cases, a preexisting subcutaneous prolapse of the stoma loop was associated with a sharp angulation at the fascial level, which was produced by the meshes. A local revision with shortening of the subcutaneous part of the stoma loop abolished the angulation and reestablished the passage. In one of these patients, the intraabdominal part of the stoma loop was perforated digitally. A formal laparotomy was necessary for repair. The patient developed a deep wound infection around the stoma as well as in the midline incision. With subsequent vacuum-assisted closure (VAC) therapy, the infected meshes could be preserved. Another patient developed an abscess in the hernia sac after a persistent seroma was punctured. Again, VAC therapy led to final preservation of the mesh and cure of the infection.

Discussion The precondition for laparoscopic intraperitoneal onlay mesh (IPOM) repair of incisional and parastomal hernias is the availability of meshes that can be incorporated into the abdominal wall but also prevent adhesions between the visceral organs and the mesh itself [12]. Up to now, most patients reported in the literature were treated with ePTFEderived meshes [6]. The visceral side, preventing adhesions, is smooth, and the parietal side is rough or covered with polypropylene to provide strong incorporation into the abdominal wall. Experimental data, however, sometimes demonstrate strong adhesions between bowel and mesh [10, 13]. Furthermore, mesh shrinkage is pronounced, leading to a 50% reduction of the original surface area [10, 14]. Also, an overlap of two ePTFE meshes does not make any sense because the scar cannot grow through the meshes, which are in fact a real foil.

The use of meshes made from polypropylene or polyester with an antiadhesive coverage represents a different approach. These meshes are effective in terms of incorporation and prevention of adhesions. The shrinkage has been shown to amount to about 20% [10, 13, 15]. No data exist concerning the incorporation behavior when two meshes are used to overlap each other. Inert material that does not adhere to visceral organs can be used as a real mesh structure, allowing an overlap of two or more meshes. The meshes can be trimmed to the ideal size, which is not possible when covered meshes are used. PVDF is a very inert material that has long been used as a suture material. Its long-term stability is even better than that of polypropylene. The inflammation reaction on a cellular level is reduced, and the amount of fibrotic tissue is lower compared with any other mesh material. The shrinkage is comparable to that for covered polypropylene structures [9, 10, 16]. From an experimental point of view, PVDF-based meshes may be clinically useful. This prospective study demonstrating clinical results in 297 patients with incisional hernias reveals promising results. The recurrence rate was very low compared with the literature. This may be explained by the size of the meshes used throughout, which was more than double that described by other authors [6, 17]. One patient developed a recurrence after explantation of the mesh. Another recurrence can only be explained by a suture-associated fascial defect, which has not been described in the literature. The pathogenesis may be similar to the tackassociated hernias described by LeBlanc [18]. The laparoscopic repair of parastomal hernias also showed very good results. As we recently demonstrated, the sandwich technique, which was used in the patients in the present study, is superior compared with the original Sugarbaker technique [11]. Despite some promising results in the literature, our own series clearly showed that the one-mesh technique according to Sugarbaker is sufficient only for medial defects of the fascia [19–21]. In cases of lateral or combined defects, two meshes are needed to stabilize the abdominal wall. A precondition of the sandwich technique is

327 Chapter 44 · IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis

the availability of a mesh material that allows the meshes to overlap each other, with stable incorporation of both meshes; ePTFE-derived meshes are foils that completely prevent any ingrowth of scar tissue in both meshes. On the other hand, the keyhole technique seems to be an attractive and technically easier alternative. In fact, there is one study with promising results [22], but the follow-up was only 6 weeks. These results, however, could not be confirmed in other studies [21, 23, 24]. Therefore, the sandwich technique seems to be the most effective approach for the repair of parastomal hernias. The only recurrence in our series was due to a surgical correction of a preexisting subcutaneous prolapse of the stoma loop. During a local revision, the subcutaneous part of the stoma loop was shortened, and the intraabdominal part with adherent small bowel loops was pulled between the two meshes. After that procedure, the patient suffered from strong pain starting immediately after any oral intake. Another major issue concerns the resistance of meshes against infection. ePTFE-derived meshes must usually be removed if an infection occurs [25, 26]. To our knowledge, nothing is known about the behavior of infected meshes covered with an antiadhesive barrier. Four patients in our series developed a deep wound and mesh infection after puncture or early surgical revision. In all cases, the meshes were preserved. Recently we published a series of 25 patients prophylactically treated with a PVDF-derived three-dimensional mesh. One patient of this series underwent early relaparotomy because of an enterotomy leading to stercoral peritonitis. After 5 days of daily revisions, the abdominal wall could be closed, and the intraperitoneal mesh could also be preserved [27]. One patient developed a secondary bowel leak due to unrecognized small bowel laceration with a fistulization through the mesh, which healed uneventfully after VAC treatment. Enterotomies that had not been recognized during the primary procedure occurred in about 2% of patients after laparoscopic incisional hernia repair. Seroma or hematoma can be observed in almost 100% of our patients because we perform routine ultrasonography after 3–5 days. In a very few patients (n=4) in this series, these seromas

44

needed to be punctured because of complaints. Three patients underwent surgical excision of the hernia sac because of a persistent seroma. These patients had a major hernia sac and a small fascial defect less than 30 cm2. According to the literature, seroma or hematoma often occurs, but only ultrasonography reveals the real rate of that complication [6, 17, 28]. Further complications are summarized in Table 44.4 and proved to be rare. The low overall complication rate supports the view that laparoscopic repair of incisional and parastomal hernias with modern meshes such as DynaMesh IPOM is an effective and safe technique. The results seem to be better than those obtained by open approaches [17]. At the least, the open repair of parastomal hernias is much more effective compared with conventional techniques [29, 30]. In summary, DynaMesh IPOM was shown to be a safe and effective mesh for the laparoscopic repair of incisional and parastomal hernias. The possibility of overlapping two or more meshes provides an ideal overlap of the abdominal wall in almost all situations and opens the way to the sandwich technique for parastomal hernia repair, which seems to be the best approach today. Infectious complications occurring in our study demonstrated the resistance of PVDF against infections. Experimental data exhibit excellent results with regard to shrinkage and adhesion formation. Overall, the described technique for laparoscopic incisional and parastomal hernia repair using DynaMesh IPOM provided satisfying results with no mesh-related complications to date.

References 1. Franz MG (2008) The biology of hernia formation. Surg Clin North Am 88:1–15 2. Millikan KW (2003) Incisional hernia repair. Surg Clin North Am 83:1223–1234 3. Luijendijk RW, Hop WC, van den Tol MP, de Lange DC, Braaksma MM, IJzermans JN, Boelhouwer RU, de Vries BC, Salu MK, Wereldsma JC, Bruijninckx CM, Jeekel J (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–398 4. Vrijland WW, Jeekel J (2003) Prosthetic mesh repair should be used for any defect in the abdominal wall. Curr Med Res Opin 19:1–3

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5. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004) Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–583 6. Carlson MA, Frantzides CT, Shostrom VK, Laguna LE (2008) Minimally invasive ventral herniorrhaphy: an analysis of 6,266 published cases. Hernia 12:9–22 7. Chelala E, Thoma M, Tatete B, Lemye AC, Dessily M, Alle JL (2007) The suturing concept for laparoscopic mesh fixation in ventral and incisional hernia repair: mid-term analysis of 400 cases. Surg Endosc 21:391–395 8. Palanivelu C, Rangarajan M, Parthasarathi R, Madankumar MV, Senthilkumar K (2008) Laparoscopic repair of suprapubic incisional hernias: suturing and intraperitoneal composite mesh onlay. A retrospective study. Hernia 12:251–256 9. Klinge U, Klosterhalfen B, Ottinger AP, Junge K, Schumpelick V (2002) PVDF as a new polymer for the construction of surgical meshes. Biomaterials 23:3487–3493 10. Junge K, Binnebosel M, Rosch R, Jansen M, Kammer D, Otto J, Schumpelick V, Klinge U (2008) Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model. Surg Endosc 23:327–333 11. Berger D, Bientzle M (2007) Laparoscopic repair of parastomal hernias: a single surgeon’s experience in 66 patients. Dis Colon Rectum 50:1668–1661 12. Berger D, Bientzle M (2006) Principles of laparoscopic incisional hernia repair. Eur Surg 38:393–398 13. McGinty JJ, Hogle NJ, McCarthy H, Fowler DL (2005) A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a porcine model using multiple types of mesh. Surg Endosc 19:786–790 14. Johnson EK, Hoyt CH, Dinsmore RC (2004) Abdominal wall hernia repair: a long-term comparison of Sepramesh and Dualmesh in a rabbit hernia model. Am Surg 70:657–661 15. Demir U, Mihmanli M, Coskun H, Dilege E, Kalyoncu A, Altinli E, Gunduz B, Yilmaz B (2005) Comparison of prosthetic materials in incisional hernia repair. Surg Today 35:223–227 16. Conze J, Junge K, Wei BC, Anurov M, Oettinger A, Klinge U, Schumpelick V (2008) New polymer for intra-abdominal meshes–PVDF copolymer. J Biomed Mater Res B Appl Biomater 87:321–328 17. Pierce RA, Spitler JA, Frisella MM, Matthews BD, Brunt LM (2007) Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual. Surg Endosc 21:378–386 18. LeBlanc KA (2003) Tack hernia: a new entity. JSLS 7:383– 387 19. Sugarbaker PH (1985) Peritoneal approach to prosthetic mesh repair of paraostomy hernias. Ann Surg 201:344– 346 20. Mancini GJ, McClusky DA, Khaitan L, Goldenberg EA, Heniford BT, Novitsky YW, Park AE, Kavic S, Le Blanc KA, Elieson MJ, Voeller GR, Ramshaw BJ (2007) Laparoscopic

21.

22.

23.

24. 25.

26.

27.

28.

29. 30.

parastomal hernia repair using a nonslit mesh technique. Surg Endosc 21:1487–1491 LeBlanc KA, Bellanger DE, Whitaker JM, Hausmann MG (2005) Laparoscopic parastomal hernia repair. Hernia 9:140–144 Hansson BM, de Hingh IH, Bleichrodt RP (2007) Laparoscopic parastomal hernia repair is feasible and safe: early results of a prospective clinical study including 55 consecutive patients. Surg Endosc 21:989–993 Muysoms F (2007) Laparoscopic repair of parastomal hernias with a modified Sugarbaker technique. Acta Chir Belg 107:476–480 Safadi B (2004) Laparoscopic repair of parastomal hernias: early results. Surg Endosc 18:676–680 Heniford BT F, Park AF, Ramshaw BJ, Voeller G (2003) Laparoscopic repair of ventral hernias: nine years’ experience with 850 consecutive hernias. Ann Surg 238:391–400 Berger D, Bientzle M, Muller A (2002) Postoperative complications after laparoscopic incisional hernia repair. Incidence and treatment. Surg Endosc 16:1720–1723 Berger D (2008) Prevention of parastomal hernias by prophylactic use of a specially designed intraperitoneal onlay mesh (Dynamesh IPST). Hernia 12:243–246 Susmalain S, Gewurtz G, Ezri T, Charuzi I (2001) Seroma after laparoscopic repair of hernia with PTFE patch: is it really a complication? Hernia 5:139–141 Carne PW, Robertson GM, Frizelle FA (2003) Parastomal hernia. Br J Surg 90:784–793 McLemore EC, Harold KL, Efron JE, Laxa BU, Young-Fadok TM, Heppell JP (2007) Parastomal hernia: short-term outcome after laparoscopic and conventional repairs. Surg Innov 14:199–204

Discussion Deysine: How did you prove the low adhesion

activity? Berger: These are only some experimental data. And the PVDF is used for bacterial filtration. And you can only use bacterial filters with low adhesions of bacteria to the filter. If you do a sterile filtration, you can use PVDF as material for the filter. Kukleta: You saw less pain after the implantation. Don’t you think it is the number of the fixation points that you use now? Do you use less than you used before? Berger: In fact, I use the same number of sutures, but I do not use as many tacks as in previous times. Klinge: Some years ago we did experimental studies with our microbiologists and looked at the

329 Chapter 44 · IPOM Results of 344 Consecutive Patients with a PVDF-Derived Prosthesis

attachment of bacteria to different materials. We quantified the amount of genetic material from the bacteria of standard meshes that had been in contact with various strains of bacteria. PVDF was not free but belonged to materials where the amount of genetic material was lowest. Schumpelick: You used fewer tacks. Why? Berger: The incorporation is better than with ePTFE. At the beginning I was convinced that we needed a permanent fixation. When I saw these incredibly shrunken dual meshes of up to 75% and all the tacks wandered with the mesh, I stopped believing in any permanent fixation. I only want to fix the mesh for a few days. Schumpelick: How does it look after 2 years? Are there long-term results available? Berger: We have done some relaparoscopies and relaparotomies and measured the mesh and found shrinkage up to 10%—not more—and the mesh was covered completely by a peritoneal layer. Peiper: The material of the mesh is one thing. The material of the fixation device is another thing. Many adhesions occur not at the mesh area but at the tacks. Do you have any experience with absorbable tacks? Berger: I have started with absorbable tacks for incisional hernia repair and always use absorbable tacks for umbilical hernias. But the company sells them for a very high price, and therefore I could not decide to completely change to absorbable tacks. Kukleta: I was using Easy tacks for 3 years. If you see adhesions, they are always at the tack, and the adhesions will even pull out the tacks. So it is exactly the same reaction that we have seen before. I use the absorbable tacks now—maybe we can afford a little more—but at the moment we do not have any results, as they have been used only for 2 or 3 months.

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Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual B. D. Matthews, R. A. Pierce, M. M. Frisella, L. M. Brunt

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Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual

Introduction

45

Incisional hernia is a common complication or consequence of abdominal surgery. In recent published series, the rate of incisional hernia after midline laparotomy has been as high as 20% [23, 26, 29, 33]. Due to recurrence rates as high as 30%, incisional hernias are not only associated with significant morbidity but may represent a significant financial strain on the healthcare system [10, 11]. Over the last decade, mesh-based repair techniques have replaced primary suture repair for most incisional hernia repairs because of an unacceptably high failure rate after primary repair [1, 6, 18, 19]. Nevertheless, open incisional hernia repair is often a major operation, with the associated risks of wound- and mesh-related infections and hernia recurrence. As an alternative approach, laparoscopic incisional hernia repair was developed and first reported in 1991 [16]. This technique is now increasingly used in the management of patients with uncomplicated as well as more complex incisional hernias. Thus far, nearly 100 studies have been published on laparoscopic ventral hernia repair, although most represent small series of patients in uncontrolled and nonrandomized trials from single institutions. The aggregate data from these studies have not been carefully analyzed on a large-scale basis, and only a single meta-analysis involving a total of eight studies has been published [13]. Prospective randomized trials comparing laparoscopic and open ventral hernia repair are ongoing in the United States and Europe. To better understand the current status of laparoscopic ventral hernia repair and critically compare it with open techniques, we examined the published literature to evaluate studies reporting on laparoscopic ventral hernia repair alone or in comparison with open ventral hernia repair.

Methods Study Selection A Medline search was performed to identify all publications involving laparoscopic ventral hernia repair from January 1996 through January 2006. Publications containing the keywords ven-

tral hernia, incisional hernia, umbilical hernia, and diastasis recti were identified and pooled. A similar search was also done on the broad-based keyword laparoscopy. These two groups were combined to isolate those references common to both and were further limited to studies conducted in humans and published in English. This final limitation produced a total of 330 publications and their accompanying abstracts. A manual review of the bibliographies of several recent publications dealing with laparoscopic ventral hernia repair did not identify any additional citations within the defined time frame that were missed. Studies were excluded from consideration if they contained fewer than 20 laparoscopic cases or if laparoscopic ventral hernia repair was not the primary focus of the article. As a result, 78 published series that contained at least 20 subjects each and dealt primarily with laparoscopic ventral hernia repair were further analyzed. These 78 studies were separated into series that compared patients who had undergone laparoscopic or open ventral hernia repair within a given institution (»paired« studies) and series that described only patients who had undergone laparoscopic ventral hernia repair (»unpaired« studies). If a single group or institution had published multiple studies, then the largest series from the group was chosen for inclusion unless the studies involved distinct, nonoverlapping patient populations. If a group had published both a paired and an unpaired study, then the paired study was chosen for analysis. Each of the 78 studies was then independently evaluated by two of three reviewers. Data extracted from each selected report included patient demographics, hernia etiology characteristics, perioperative details, postoperative complications, and hernia recurrence. All studies that provided sufficient detail regarding complications and recurrences were included in the analysis, even if some variables (e.g., mean hernia size) were missing. Any discrepancies were resolved by consensus of all investigators after reviewing the primary data again. This process led to the final selection of 45 total studies (14 paired, 31 unpaired), which are listed in Appendices 45.1 and 45.2. Intraoperative parameters that were evaluated included operating time, hernia and mesh sizes, open hernia repair technique (mesh vs. primary suture), open conversion for laparoscopic cases, and

333 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

complications. Postoperative information on hospital length of stay (LOS), complications, follow-up duration, hernia recurrence, mortality, and cost of hospitalization were all recorded. Complications related to the surgical procedure, including wound problems, mesh infection, trocar site hernia, seroma, and need for early reoperation, were evaluated. Other postoperative complications were classified into the following categories: cardiac, pulmonary, gastrointestinal, genitourinary, thromboembolic, septic, neurologic/psychiatric, prolonged pain, and miscellaneous. The perioperative mortality rate was analyzed independently, but the principal cause of death was also included as a complication.

Statistical Methods Statistical analysis was performed by an independent statistician. Two separate data sets were analyzed (paired studies comparing laparoscopic to open ventral hernia repair and unpaired studies of laparoscopic ventral hernia repair only). Data from the paired studies were analyzed as the primary evaluation and designated the »paired« analysis. Additionally, data from the unpaired laparoscopic ventral hernia repair studies were combined with the laparoscopic ventral hernia repair data from the paired studies to create a pooled laparoscopic ventral hernia repair group. These pooled laparoscopic ventral hernia repair data were then compared with the open ventral hernia repair data from the paired studies and designated the »pooled« analysis. In three instances, a given group had published both a paired study as well as a more recent, larger unpaired study that appeared to incorporate the laparoscopic ventral hernia repair cases from the smaller paired study. In these situations, the laparoscopic ventral hernia repair cases in the paired study were included in the paired analysis, but they were excluded from the combined analysis in lieu of the larger unpaired cohort. The strategy behind this dual analysis (paired and pooled) was that the paired analysis should have the greatest amount of internal validity, as the same groups of surgeons were performing both the open and laparoscopic cases and so it was much more likely that the patients undergoing either

45

laparoscopic or open ventral hernia repair in these studies would have been selected from the same respective patient populations. In addition, comparing the results of the paired analysis to those derived from the tenfold larger laparoscopic ventral hernia repair group used for the pooled analysis allows for external validation and extrapolation to a more global patient population. In several series, the patient populations were split into smaller subpopulations, and mean values were given for these subgroups. In these instances, a conglomerate weighted mean was calculated and used in the final analysis. Likewise, many of the studies did not report standard deviations in their statistical analyses, so weighted means were used to perform the calculations. Accordingly, a two-tailed t-test was used to compare differences in these weighted means, and any studies that had missing data points were taken into account when performing the analysis. Because the raw numbers of complications, recurrences, and deaths were available in all the studies that were evaluated, these parameters were amenable to more thorough statistical analyses. Thus, totals for these data points were calculated for both the laparoscopic and open ventral hernia repair groups, and differences between them were determined using chi-square analysis. Alternatively, Fisher’s exact test was used in the event that the number of data points was too small to allow for use of a chi-square algorithm.

Results A total of 45 reports met the inclusion criteria, including 14 paired and 31 unpaired studies. The majority of these studies were retrospective (n=33; 73%), whereas three of the paired and nine of the unpaired studies were done in a prospective fashion (12 total; 27%). These reports encompassed a total of 5,340 patients, including 4,582 (86%) who had undergone laparoscopic ventral hernia repair and 758 (14%) who had open ventral hernia repair. Of those 4,582 patients who underwent laparoscopic ventral hernia repair, 619 (14%) were reported in paired studies and 87% were from unpaired studies. Demographic data from the 45 studies are shown in ⊡ Table 45.1. The mean patient age was 55.3 years

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in the pooled laparoscopic group, 52.9 years in the paired laparoscopic group, and 56.1 years in those receiving open repairs (not significant). Only 19 series reported the body mass index (BMI), five of which were paired studies. In the five paired series, the weighted mean BMI was 30.5 for laparoscopic cases and 29.5 for the open cases (not significant). In the pooled group, the laparoscopic repair patients had a somewhat higher mean BMI of 32.6 compared with the open repair patients (p=0.0026). Each study was also examined for the numbers of primary vs. incisional hernias and recurrent hernias. Few series included all three data points; however, 12 of the 14 paired and 27 of the 31 unpaired studies documented the number of recurrent hernias that were operated. Among the open group, 25.2% of the hernias were recurrent, compared to 27.5% of those done laparoscopically in only the

paired studies and 28.5% of cases from the combined laparoscopic group. Two paired studies [12, 34] that focused solely on umbilical hernias were included in the analysis. Both were paired studies, and all of their open repairs were done using mesh. Conversely, two other paired studies [15, 28] reported repairing some of their smaller ventral hernias using a primary sutured technique. However, these 24 cases of primary closure represented only 4.4% of the total number of open repairs. All laparoscopic repairs were done using intraperitoneal mesh. Operative data are shown in ⊡ Table 45.2. The mean operating time for the laparoscopic cases in the paired studies was 119.6 min, and 100.3 min when all the laparoscopic procedures are considered. The mean operating time for open repairs falls between these two times at 104.5 min. The hernia defect size (70.8 cm2) and the size of the mesh used

⊡ Table 45.1. Patient demographics p-valuea

p-valueb

Open repairs

Paired laparoscopic cases

Patient number (n)

758

619

4,582

Percent male

49

49

44

Age (years)

56.1

52.9

0.13

55.3

0.49

Body mass index

29.5

30.5

0.57

32.6

0.003

Length of stay (days)

4.3

2.4

0.015

2.4

0.0004

Follow-up time (months)

20.2

16.9

0.47

25.5

0.16

aCompares bCompares

Pooled laparoscopic cases

open group to paired laparoscopic ventral hernia repair group open group to pooled laparoscopic ventral hernia repair group

⊡ Table 45.2. Operative data Open repairs

Paired laparoscopic cases

p-valuea

Pooled laparoscopic cases

p-valueb

Operating time (min)

104.5

115.0

0.40

100.3

0.61

Recurrent hernias (%)

25.2

27.5

Hernia size

(cm2)

28.5

70.8

87.9

0.40

103.4

0.025

Mesh size (cm2)

170.1

260.9

0.27

295.2

0.009

Enterotomy rate (%)

1.2

2.9

0.022

2.1

0.11

Conversion rate (%) aCompares bCompares

3.9

open group with paired laparoscopic ventral hernia repair group open group with pooled laparoscopic ventral hernia repair group

3.5

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335 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

for repair (175.5 cm2) were smallest in the patients undergoing open repair. The values are somewhat larger (87.9 cm2 and 260.9 cm2) when compared directly to the patients undergoing laparoscopic repair in the same set of paired studies. However, the larger hernia and mesh sizes become even more apparent when all the laparoscopic cases in the pooled group are considered (103.4 cm2, p=0.025 and 295.2 cm2, p=0.009, respectively). The enterotomy rate was significantly higher in paired laparoscopic ventral hernia repair cases compared to open ventral her-

nia repair (2.9% vs. 1.2%). Postoperative LOS was significantly shorter for the laparoscopic repairs, averaging 2.4 days in both paired and pooled laparoscopic ventral hernia repair groups compared with 4.3 days after open ventral hernia repair (p=0.015 and 0.0004, respectively). Total complication rates were significantly higher with open ventral hernia (41.6%) compared to laparoscopic ventral hernia repair for both pooled (22.7%) and paired (25.5%) analyses (p<0.0001; ⊡ Fig. 45.1). In the analysis of complications by or-

45 40

* p<0.0001

Incidence (%)

35 30

*

25

*

20 15 10 5 0

OPEN

PAIRED LAP

POOLED LAP

⊡ Fig. 45.1. Total complications

⊡ Table 45.3. Organ system complications (NS not significant) Open repairs (%)

Paired laparoscopic cases (%)

p-valuea

Pooled laparoscopic cases (%)

p-valueb

Gastrointestinal

5.9

4.0

0.11

2.6

<0.0001

Cardiac

0.5

0

0.13

0.2

0.10

Pulmonary

1.7

0.8

0.14

0.6

0.0013

Septic

0

0

NS

0.02

1.0

Thromboembolic

0.3

0.2

1.0

0.1

0.20

Genitourinary

1.6

1.1

0.47

0.9

0.10

Neurological

0.1

0

1.0

0.02

0.26

Prolonged pain

0.9

1.0

0.93

2.0

0.047

Miscellaneous complicationsc

1.9

1.0

0.18

0.7

0.0011

Mortality

0.3

0.3

1.0

0.1

0.32

aCompares

open group with paired laparoscopic ventral hernia repair group open group with pooled laparoscopic ventral hernia repair group cIncludes fever, superficial thrombophlebitis, and psychiatric complications bCompares

336

gan system, the pooled laparoscopic ventral hernia repair studies reported significantly fewer wound, pulmonary, and gastrointestinal complications compared to the open ventral hernia repair series (⊡ Table 45.3). Only total and wound complication rates were significantly different in the paired study comparison. No significant differences were noted for rates of cardiac, thromboembolic, urologic, or neurologic complications between any of the study groups. In the pooled laparoscopic ventral hernia repair group, prolonged postoperative pain was reported in a significantly greater percentage of patients (1.9%) compared to the open ventral hernia repair group (0.92%); however, prolonged

pain rates were similar for the open and laparoscopic ventral hernia repair paired series. Mortality rates were also similar between groups. Wound infection rates were 4.6–8-fold higher in the open versus laparoscopic ventral hernia repair series for both pooled and paired study comparisons and accounted for most of the wound-related complications (⊡ Table 45.4). The number of mesh infections was also significantly higher with open ventral hernia repair for all comparisons. Interestingly, the incidence of postoperative seroma was similar for both open and laparoscopic series. The rate of hernia recurrence (⊡ Fig. 45.2) was significantly lower with laparoscopic ventral her-

14 12 10 Incidence (%)

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Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual

* p<0.0001

8 6

*

4

*

2 0 ⊡ Fig. 45.2. Hernia recurrence

OPEN

PAIRED LAP

POOLED LAP

⊡ Table 45.4. Wound complications Open repairs (%)

Paired laparoscopic cases (%)

p-valuea

Pooled laparoscopic cases (%)

p-valueb

Wound infection

10.4

2.3

<0.0001

1.3

<0.0001

Total wound complicationsc

16.8

5.3

<0.0001

3.8

<0.0001

Mesh infection

3.2

1.5

0.039

0.9

<0.0001

Seroma

12.0

12.1

0.95

11.5

0.66

Trocar hernia aCompares

0

0.4

open group with paired laparoscopic ventral hernia repair group Compares open group with pooled laparoscopic ventral hernia repair group cIncludes wound hematoma/bleeding, cellulitis, dehiscence, and fat necrosis in addition to wound infection b

337 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

nia repair for both the pooled (4.3%) and paired (3.1%) study cohorts compared to the paired open ventral hernia repair series (12.1%, both p<0.0001). Small variations existed in the length of follow-up reported in the three groups of studies (25.5 months for pooled laparoscopic ventral hernia repair, 16.9 months for paired laparoscopic ventral hernia repair, 20.2 months for open ventral hernia repair), but these differences were not significant. The reported incidence of trocar site hernia in the laparoscopic series was only 0.35%.

Discussion Large, single, and multi-institutional series have reported excellent results with few complications and recurrence rates of generally <10% after laparoscopic ventral hernia repair [3, 4, 8, 14, 17, 22, 27, 32]. However, only one prospective, randomized, controlled trial comparing laparoscopic to open incisional hernia repair [7] and one looking at laparoscopic versus open repair of Spigelian hernias have been reported [21]. Despite the growing body of knowledge in the field of laparoscopic ventral hernia repair, published overviews of the topic are largely review papers that have not pooled the data and critically analyzed it as a whole [9]. A single meta-analysis evaluating eight studies and three data sets (perioperative complications, operating time, and hospital LOS) has been published [13]. The most stringent statistical method for analyzing any published data from multiple sources is a meta-analysis, requiring completeness and uniformity in the data reporting methods. Any studies that lack a data point of interest, or that fail to report standard deviations along with their means, must be excluded from analysis. Such an approach in the area of ventral hernia repair would exclude many potentially informative studies because of the variable reporting methods used in these reports. A pooled-data analysis of laparoscopic ventral hernia repair was performed in order to encompass a broad range of papers and achieve a more complete overview of the results and outcomes. Dividing the study population into »paired« and »pooled« groups allowed us to examine one cohort that should have a high degree

45

of internal consistency for comparison with open ventral hernia repair (the paired studies only), as well as a significantly larger group (the pooled studies) that should give a broader view of the field as a whole; this approach has proven useful in similar past analyses [33]. In our analysis, we found the patient populations in both the pooled and paired laparoscopic groups, as well as in the open surgery group, to be demographically similar. All cohorts show a similar gender distribution, and the mean patient ages across the groups of studies show little variation. The vast majority of patients in the reported series were clinically overweight or obese, not surprising given that obesity is a strong predictive factor in hernia formation and recurrence [24, 30, 31]. The analysis of perioperative data showed that operative times were not significantly different for open or laparoscopic approaches. However, there was considerable variation across studies in the laparoscopic operative technique used, with some groups employing transfixion sutures routinely and others using them in a limited fashion or using only tacks. The variability in laparoscopic technique and the fact that most series included cases that were part of the institution’s early experience limit any definite conclusions about operative time comparisons. The measured size of the hernia defect and the size of mesh used, however, were greater in the laparoscopic reports than for the open patients, although these differences were significant for the pooled laparoscopic studies only. Possible explanations for these findings are that patients with larger defects are being selected for laparoscopic repair, the laparoscopic series are measuring sizes of all the combined defects whereas open reports describe the size of the largest defect only, additional defects are being detected and repaired with laparoscopic ventral hernia repair, or a combination of these variables. Similarly, it is not surprising that a larger mesh size was used with laparoscopic ventral hernia repair because of the technique of covering all defects with a single piece of mesh without needing to dissect large tissue flaps as with open ventral hernia repair. Postoperative LOS for both the pooled and paired laparoscopic groups averaged only 2.4 days compared to 4.3 days for the open group. The

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Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual

reasons for shorter hospitalization with the laparoscopic approach are unclear but could be related to fewer complications, as discussed below, among other variables. A shorter hospitalization could also be a factor in the potential economic impact of laparoscopic ventral hernia repair, as recently addressed by Earle et al. [11]. The primary outcome parameters were perioperative complications and hernia recurrences. The analysis demonstrates that laparoscopic ventral hernia repair was associated with a significantly lower overall complication rate compared to open ventral hernia repair in the paired analysis. This difference was due primarily to more wound complications in the open ventral hernia repair series. Some differences were also seen in other organ system complications when the pooled laparoscopic ventral hernia repair data were compared to open ventral hernia repair for gastrointestinal, pulmonary, and miscellaneous other complications such as fever and thrombophlebitis; however, these differences did not reach statistical significance in the paired comparison because of the smaller sample size. Another explanation for the differences in other organ system complications in the pooled analysis is that groups reporting only on their laparoscopic experiences (i.e., studies included only in the pooled analysis) may have accumulated more extensive experience and achieved better outcomes with the laparoscopic procedure. One of the main potential advantages of laparoscopic incisional hernia repair is reduced wound complications and mesh infections, and the results of our meta-analysis support this. The difference in wound complication rates between laparoscopic versus open cases is largely a reflection of the decreased number of wound infections seen in the laparoscopic group. Two major factors likely contribute to a reduced infection rate. First, open incisional hernia repair typically involves extensive lateral dissection of tissue planes, with a large subcutaneous dead space and potentially altered blood flow. The mesh is often exposed to the subcutaneous space, with the potential for subsequent infection if a superficial wound infection occurs. With the laparoscopic approach, there is no flap dissection, and the mesh is placed intraperitoneally. Second, unlike laparoscopic ventral

hernia repair, during open ventral hernia repair the prosthetic mesh is more likely to contact the patient’s skin, with the potential for seeding by residual dermal flora. There was no difference in the rate of clinically significant seroma formation between the laparoscopic and open ventral hernia repair groups. One complication that occurred somewhat more frequently in the laparoscopic group in the paired analysis was enterotomy (2.9% laparoscopic vs. 1.2% open). Enterotomy during ventral hernia repair is a major complication with potentially lifethreatening consequences if unrecognized. The enterotomies recorded in this analysis included both those that were recognized at the time of surgery as well as those discovered later due to a subsequent complication. The occurrence of enterotomy is probably related to multiple variables, including surgeon experience, but most likely the primary risk variable is the extent of intraabdominal adhesions. The presence of prior mesh hernia repair may also be a factor in the risk for enterotomy during laparoscopic incisional hernia repair. In one recent series, the incidence of enterotomy during laparoscopic ventral hernia repair in patients with prior mesh placed was 11.4% compared with no enterotomies in patients who had not had previous mesh repairs [25] . Early postoperative pain was not evaluated in this analysis, but prolonged pain was recorded in a somewhat higher percentage of patients in the pooled laparoscopic series compared to open, but not in the paired analysis. These differences could be accounted for in part by variable reporting methods of prolonged pain as a »complication.« However, unlike most other laparoscopic procedures in which incisional pain is typically minimal, laparoscopic incisional hernia repair is associated with substantially more pain in the postoperative period because of the methods of mesh fixation. Specifically, the use of transfixion sutures for the mesh has been associated with increased pain after laparoscopic ventral hernia repair, but this issue was not addressed in our analysis. The most important measure of an effective hernia operation is a low recurrence rate. In the paired and pooled data sets, laparoscopic ventral hernia repair was associated with significantly

339 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

fewer hernia recurrences. These results do not appear to be explained on the basis of inadequate or short follow-up periods (mean 17–25 months), although longer-term studies with examination at follow-up will ultimately be necessary to verify these claims. Possible reasons for the lower recurrence rate with laparoscopic ventral hernia repair are that wide areas of tissue–prosthesis overlap can be obtained. This broad interface should allow for better tissue–mesh integration and a stronger repair with subsequent lower recurrence rates. A laparoscopic approach also provides a better opportunity to identify all hernia defects, some of which could be missed with an open approach. It is important to consider some of the limitations of the data analysis. One potential shortcoming of this study is the lack of complete statistical analysis of all data points studied. This, however, is largely due to inconsistent reporting of these data points across the studies evaluated. All the examined series reported their total number of patients; greater than 95% reported mean patient age; and approximately 85–90% gave information on gender breakdowns, operative times, hospital LOS, and duration of follow-up. In contrast, only about one-half to two-thirds of the studies gave information on hernia and mesh size, and fewer than 50% reported patient BMI values. Furthermore, only six reports, all of them paired studies, gave any information on the costs associated with the operative procedure and/or the hospital stay [2, 5, 10, 15, 20, 35]. Even in instances in which these parameters were reported, the values were sometimes given as means and sometimes as medians, and they often did not include standard deviations. Lack of such detailed information limits the statistical analyses that can be applied and precludes any formal meta-analysis of the data points unless a large number of studies with incomplete data are excluded.

Conclusions An analysis of the published literature on laparoscopic ventral hernia repair shows that this procedure is associated with lower total complication rates and fewer wound and mesh infections

45

than with open ventral hernia mesh repair. Hernia recurrence rates in short-term to medium-term follow-up are acceptably low and are significantly less than those reported in paired open ventral hernia cases. Studies with longer-term follow-up will be necessary to verify these results. Despite the limitations of this pooled-data analysis, it appears that laparoscopic incisional hernia repair has several distinct advantages over open approaches. Laparoscopic repair should be strongly considered by surgeons with appropriate advanced laparoscopic expertise for patients with noncomplex incisional hernias.

Acknowledgments The authors wish to thank Dr. Yan-Yan in the Department of Surgery and the Siteman Cancer Center, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri, for statistical support.

References 1. Anthony T, Bergen PC, Kim LT, Henderson M, Fahey T, Rege RV, Turnage RH (2000) Factors affecting recurrence following incisional herniorrhaphy. World J Surg 24:95–100 2. Beldi G, Ipaktchi R, Wagner M, Gloor B, Candinas D (2006) Laparoscopic ventral hernia repair is safe and cost effective. Surg Endosc 20:92–95 3. Ben-Haim M, Kuriansky J, Tal R, Zmora O, Mintz Y, Rosin D, Ayalon A, Shabtai M (2002) Pitfalls and complications with laparoscopic intraperitoneal expanded polytetrafluoroethylene patch repair of postoperative ventral hernia. Surg Endosc 16:785–788 4. Bencini L, Sanchez LJ (2004) Learning curve for laparoscopic ventral hernia repair. Am J Surg 187:378–382 5. Bencini L, Sanchez LJ, Boffi B, Farsi M, Scatizzi M, Moretti R (2003) Incisional hernia: repair retrospective comparison of laparoscopic and open techniques. Surg Endosc 17:1546–1551 6. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004) Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–583 7. Carbajo MA, Martin del Olmo JC, Blanco JI, de la CC, Toledano M, Martin F, Vaquero C, Inglada L (1999) Laparoscopic treatment vs open surgery in the solution of major incisional and abdominal wall hernias with mesh. Surg Endosc 13:250–252

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8. Carbajo MA, Martin del Olmo JC, Blanco JI, Toledano M, de la CC, Ferreras C, Vaquero C (2003) Laparoscopic approach to incisional hernia. Surg Endosc 17:118–122 9. Cobb WS, Kercher KW, Heniford BT (2005) Laparoscopic repair of incisional hernias. Surg Clin North Am 85:91– 103, ix 10. DeMaria EJ, Moss JM, Sugerman HJ (2000) Laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch repair of ventral hernia. Prospective comparison to open prefascial polypropylene mesh repair. Surg Endosc 14:326–329 11. Earle D, Seymour N, Fellinger E, Perez A (2006) Laparoscopic versus open incisional hernia repair: a singleinstitution analysis of hospital resource utilization for 884 consecutive cases. Surg Endosc 20:71–75 12. Gonzalez R, Mason E, Duncan T, Wilson R, Ramshaw BJ (2003) Laparoscopic versus open umbilical hernia repair. JSLS 7:323–328 13. Goodney PP, Birkmeyer CM, Birkmeyer JD (2002) Shortterm outcomes of laparoscopic and open ventral hernia repair: a meta-analysis. Arch Surg 137:1161–1165 14. Heniford BT, Park A, Ramshaw BJ, Voeller G (2003) Laparoscopic repair of ventral hernias: nine years’ experience with 850 consecutive hernias. Ann Surg 238:391–399 15. Holzman MD, Purut CM, Reintgen K, Eubanks S, Pappas TN (1997) Laparoscopic ventral and incisional hernioplasty. Surg Endosc 11:32–35 16. LeBlanc KA, Booth WV (1993) Laparoscopic repair of incisional abdominal hernias using expanded polytetrafluoroethylene: preliminary findings. Surg Laparosc Endosc 3:39–41 17. LeBlanc KA, Booth WV, Whitaker JM, Bellanger DE (2000) Laparoscopic incisional and ventral herniorrhaphy in 100 patients. Am J Surg 180:193–197 18. Luijendijk RW, Hop WC, van den Tol MP, de L, Braaksma MM, IJzermans JN, Boelhouwer RU, de Vries BC, Salu MK, Wereldsma JC, Bruijninckx CM, Jeekel J (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–398 19. Luijendijk RW, Lemmen MH, Hop WC, Wereldsma JC (1997) Incisional hernia recurrence following «vest-overpants» or vertical Mayo repair of primary hernias of the midline. World J Surg 21:62–65 20. McGreevy JM, Goodney PP, Birkmeyer CM, Finlayson SR, Laycock WS, Birkmeyer JD (2003) A prospective study comparing the complication rates between laparoscopic and open ventral hernia repairs. Surg Endosc 17:1778– 1780 21. Moreno-Egea A, Carrasco L, Girela E, Martin JG, Aguayo JL, Canteras M (2002) Open vs laparoscopic repair of spigelian hernia: a prospective randomized trial. Arch Surg 137:1266–1268 22. Moreno-Egea A, Torralba JA, Girela E, Corral M, Bento M, Cartagena J, Vicente JP, Aguayo JL, Canteras M (2004) Immediate, early, and late morbidity with laparoscopic ventral hernia repair and tolerance to composite mesh. Surg Laparosc Endosc Percutan Tech 14:130–135

23. Mudge M, Hughes LE (1985) Incisional hernia: a 10 year prospective study of incidence and attitudes. Br J Surg 72:70–71 24. Novitsky YW, Cobb WS, Kercher KW, Matthews BD, Sing RF, Heniford BT (2006) Laparoscopic ventral hernia repair in obese patients: a new standard of care. Arch Surg 141:57–61 25. Perrone JM, Soper NJ, Eagon JC, Klingensmith ME, Aft RL, Frisella MM, Brunt LM (2005) Perioperative outcomes and complications of laparoscopic ventral hernia repair. Surgery 138:708–715 26. Read RC, Yoder G (1989) Recent trends in the management of incisional herniation. Arch Surg 124:485–488 27. Rosen M, Brody F, Ponsky J, Walsh RM, Rosenblatt S, Duperier F, Fanning A, Siperstein A (2003) Recurrence after laparoscopic ventral hernia repair. Surg Endosc17:123–128 28. Salameh JR, Sweeney JF, Graviss EA, Essien FA, Williams MD, Awad S, Itani KM, Fisher WE (2002) Laparoscopic ventral hernia repair during the learning curve. Hernia 6:182–187 29. Sorensen LT, Hemmingsen UB, Kirkeby LT, Kallehave F, Jorgensen LN (2005) Smoking is a risk factor for incisional hernia. Arch Surg 140:119–123 30. Sugerman HJ (1998) Increased intra-abdominal pressure in obesity. Int J Obes Relat Metab Disord 22:1138 31. Sugerman HJ (2001) Effects of increased intra-abdominal pressure in severe obesity. Surg Clin North Am 81:1063–75, vi 32. Ujiki MB, Weinberger J, Varghese TK, Murayama KM, Joehl RJ (2004) One hundred consecutive laparoscopic ventral hernia repairs. Am J Surg 188:593–597 33. Winslow ER, Fleshman JW, Birnbaum EH, Brunt LM (2002) Wound complications of laparoscopic vs open colectomy. Surg Endosc 16:1420–1425 34. Wright BE, Beckerman J, Cohen M, Cumming JK, Rodriguez JL (2002) Is laparoscopic umbilical hernia repair with mesh a reasonable alternative to conventional repair? Am J Surg 184:505–508 35. Wright BE, Niskanen BD, Peterson DJ, Ney AL, Odland MD, VanCamp J, Zera RT, Rodriguez JL (2002) Laparoscopic ventral hernia repair: are there comparative advantages over traditional methods of repair? Am Surg 68:291–295

Appendix 45.1 Paired Series Included in Study 1. Beldi G, Ipaktchi R, Wagner M, Gloor B, Candinas D (2006) Laparoscopic ventral hernia repair is safe and cost effective. Surg Endosc 20:92–95 2. Bencini L, Sanchez LJ, Boffi B, Farsi M, Scatizzi M, Moretti R (2003) Incisional hernia: repair retrospective comparison of laparoscopic and open techniques. Surg Endosc 17:1546–1551 3. Carbajo MA, Martin del Olmo JC, Blanco JI, de la CC, Toledano M, Martin F, Vaquero C, Inglada L (1999) Laparoscopic treatment vs open surgery in the solution of major incisional and abdominal wall hernias with mesh. Surg Endosc 13:250–252

341 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

4. DeMaria EJ, Moss JM, Sugerman HJ (2000) Laparoscopic intraperitoneal polytetrafluoroethylene (PTFE) prosthetic patch repair of ventral hernia. Prospective comparison to open prefascial polypropylene mesh repair. Surg Endosc 14:326–329 5. Gonzalez R, Mason E, Duncan T, Wilson R, Ramshaw BJ (2003) Laparoscopic versus open umbilical hernia repair. JSLS 7:323–328 6. Holzman MD, Purut CM, Reintgen K, Eubanks S, Pappas TN (1997) Laparoscopic ventral and incisional hernioplasty. Surg Endosc 11:32–35 7. McGreevy JM, Goodney PP, Birkmeyer CM, Finlayson SR, Laycock WS, Birkmeyer JD (2003) A prospective study comparing the complication rates between laparoscopic and open ventral hernia repairs. Surg Endosc 17:1778– 1780 8. Park A, Birch DW, Lovrics P (1998) Laparoscopic and open incisional hernia repair: a comparison study. Surgery 124:816–821 9. Raftopoulos I, Vanuno D, Khorsand J, Kouraklis G, Lasky P (2003) Comparison of open and laparoscopic prosthetic repair of large ventral hernias. JSLS 7:227–232 10. Ramshaw BJ, Esartia P, Schwab J, Mason EM, Wilson RA, Duncan TD, Miller J, Lucas GW, Promes J (1999) Comparison of laparoscopic and open ventral herniorrhaphy. Am Surg 65:827–831 11. Salameh JR, Sweeney JF, Graviss EA, Essien FA, Williams MD, Awad S, Itani KM, Fisher WE (2002) Laparoscopic ventral hernia repair during the learning curve. Hernia 6:182–187 12. van’t Riet RM, de Vos van Steenwijk PJ, Bonthuis F, Marquet RL, Steyerberg EW, Jeekel J, Bonjer HJ (2003) Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model. Ann Surg 237:123–128 13. Wright BE, Beckerman J, Cohen M, Cumming JK, Rodriguez JL (2002) Is laparoscopic umbilical hernia repair with mesh a reasonable alternative to conventional repair? Am J Surg 184:505–508 14. Wright BE, Niskanen BD, Peterson DJ, Ney AL, Odland MD, VanCamp J, Zera RT, Rodriguez JL (2002) Laparoscopic ventral hernia repair: are there comparative advantages over traditional methods of repair? Am Surg 68:291–295

Appendix 45.2 Unpaired Series Included in Study 1. Aura T, Habib E, Mekkaoui M, Brassier D, Elhadad A (2002) Laparoscopic tension-free repair of anterior abdominal wall incisional and ventral hernias with an intraperitoneal Gore-Tex mesh: prospective study and review of the literature. J Laparoendosc Adv Surg Tech A 12:263–267 2. Bageacu S, Blanc P, Breton C, Gonzales M, Porcheron J, Chabert M, Balique JG (2002) Laparoscopic repair of incisional hernia: a retrospective study of 159 patients. Surg Endosc 16:345–348 3. Bamehriz F, Birch DW (2004) The feasibility of adopting laparoscopic incisional hernia repair in general surgery

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

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practice: early outcomes in an unselected series of patients. Surg Laparosc Endosc Percutan Tech 14:207–209 Ben-Haim M, Kuriansky J, Tal R, Zmora O, Mintz Y, Rosin D, Ayalon A, Shabtai M (2002) Pitfalls and complications with laparoscopic intraperitoneal expanded polytetrafluoroethylene patch repair of postoperative ventral hernia. Surg Endosc 16:785–788 Berger D, Bientzle M, Muller A (2002) Postoperative complications after laparoscopic incisional hernia repair. Incidence and treatment. Surg Endosc 16:1720–1723 Bingener J, Kazantsev GB, Chopra S, Schwesinger WH (2004) Adhesion formation after laparoscopic ventral incisional hernia repair with polypropylene mesh: a study using abdominal ultrasound. JSLS 8:127–131 Birgisson G, Park AE, Mastrangelo MJ, Jr., Witzke DB, Chu UB (2001) Obesity and laparoscopic repair of ventral hernias. Surg Endosc 15:1419–1422 Bower CE, Reade CC, Kirby LW, Roth JS (2004) Complications of laparoscopic incisional-ventral hernia repair: the experience of a single institution. Surg Endosc 18:672– 675 Carbajo MA, Martp del Olmo JC, Blanco JI, Toledano M, de la CC, Ferreras C, Vaquero C (2003) Laparoscopic approach to incisional hernia. Surg Endosc 17:118–122 Chelala E, Gaede F, Douillez V, Dessily M, Alle JL (2003) The suturing concept for laparoscopic mesh fixation in ventral and incisional hernias: preliminary results. Hernia 7:191–196 Chowbey PK, Sharma A, Khullar R, Mann V, Baijal M, Vashistha A (2000) Laparoscopic ventral hernia repair. J Laparoendosc Adv Surg Tech A 10:79–84 Eid GM, Prince JM, Mattar SG, Hamad G, Ikrammudin S, Schauer PR (2003) Medium-term follow-up confirms the safety and durability of laparoscopic ventral hernia repair with PTFE. Surgery 134:599–603 Franklin ME, Jr., Gonzalez JJ, Jr., Glass JL, Manjarrez A (2004) Laparoscopic ventral and incisional hernia repair: an 11-year experience. Hernia 8:23–27 Heniford BT, Park A, Ramshaw BJ, Voeller G (2003) Laparoscopic repair of ventral hernias: nine years’ experience with 850 consecutive hernias. Ann Surg 238:391–399 Kannan K, Ng C, Ravintharan T (2004) Laparoscopic ventral hernia repair: local experience. Singapore Med J 45:271–275 Kua KB, Coleman M, Martin I, O’Rourke N (2002) Laparoscopic repair of ventral incisional hernia. ANZ J Surg 72:296–299 Kyzer S, Alis M, Aloni Y, Charuzi I (1999) Laparoscopic repair of postoperation ventral hernia. Early postoperation results. Surg Endosc 13:928–931 LeBlanc KA, Whitaker JM, Bellanger DE, Rhynes VK (2003) Laparoscopic incisional and ventral hernioplasty: lessons learned from 200 patients. Hernia 7:118–124 Mizrahi S, Lantsberg L, Kirshtein B, Bayme M, Avinoah E (2003) The experience with a modified technique for laparoscopic ventral hernia repair. J Laparoendosc Adv Surg Tech A 13:305–307

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20. Moreno-Egea DA, Martinez JA, Cuenca GM, Miquel JD, Lorenzo JG, Albasini JL, Jordana MC (2004) Mortality following laparoscopic ventral hernia repair: lessons from 90 consecutive cases and bibliographical analysis. Hernia 8:208–212 21. Muysoms F, Daeter E, Vander MG, Claeys D (2004) Laparoscopic intraperitoneal repair of incisional and ventral hernias. Acta Chir Belg 104:705–708 22. Parker HH, III, Nottingham JM, Bynoe RP, Yost MJ (2002) Laparoscopic repair of large incisional hernias. Am Surg 68:530–533 23. Perrone JM, Soper NJ, Eagon JC, Klingensmith ME, Aft RL, Frisella MM, Brunt LM (2005) Perioperative outcomes and complications of laparoscopic ventral hernia repair. Surgery 138:708–715 24. Reitter DR, Paulsen JK, Debord JR, Estes NC (2000) Fiveyear experience with the »four-before« laparoscopic ventral hernia repair. Am Surg 66:465–468 25. Rosen M, Brody F, Ponsky J, Walsh RM, Rosenblatt S, Duperier F, Fanning A, Siperstein A (2003) Recurrence after laparoscopic ventral hernia repair. Surg Endosc 17:123– 128 26. Sanchez LJ, Bencini L, Moretti R (2004) Recurrences after laparoscopic ventral hernia repair: results and critical review. Hernia 8:138–143 27. Szymanski J, Voitk A, Joffe J, Alvarez C, Rosenthal G (2000) Technique and early results of outpatient laparoscopic mesh onlay repair of ventral hernias. Surg Endosc 14:582– 584 28. Toy FK, Bailey RW, Carey S, Chappuis CW, Gagner M, Josephs LG, Mangiante EC, Park AE, Pomp A, Smoot RT, Jr., Uddo JF, Jr., Voeller GR (1998) Prospective, multicenter study of laparoscopic ventral hernioplasty. Preliminary results. Surg Endosc 12:955–959 29. Tsimoyiannis EC, Siakas P, Glantzounis G, Koulas S, Mavridou P, Gossios KI (2001) Seroma in laparoscopic ventral hernioplasty. Surg Laparosc Endosc Percutan Tech 11:317–321 30. Ujiki MB, Weinberger J, Varghese TK, Murayama KM, Joehl RJ (2004) One hundred consecutive laparoscopic ventral hernia repairs. Am J Surg 188:593–597 31. Verbo A, Petito L, Pedretti G, Lurati M, D’Alba P, Coco C (2004) Use of a new type of PTFE mesh in laparoscopic incisional hernia repair: the continuing evolution of technique and surgical expertise. Int Surg 89:27–31

Discussion Deysine: If I were a reviewer of this paper, I would address the need of a pooled data analysis. However, it is very difficult to compare unpaired data. So the valid comparison would be a data analysis with paired groups. In the main table you produced, there was no major difference in several

outcomes between open and laparoscopic [procedures], and you had to pull additional data without comparative analysis to make a strong point in favor of laparotomy. Matthews: If you look at the pooled data, you could say that is from laparoscopic experts, and is that really applicable to the community surgeon who does everything? So you are right. If you look at the paired analysis, everything looks very similar in terms of those patient variables. Obviously, there were some differences with the complications. You could argue that a laparoscopic ventral hernia repair should be done by an expert hernia surgeon. In a meta-analysis, you can work the data however you want it to come out. Kukleta: Concerning the prolonged pain, in the pooled group you found an increase on the laparoscopic side. Was there any possibility to take a look at the technique of transfascial sutures and the material used, because there are 25 U.S. papers where, in most, ePTFE was used. Here fixation must be stronger than everywhere else. Did you find any correlation? Matthews: You are absolutely right. Greater than 90% of our pooled data used an ePTFE mesh. So there are some additional things that we can look at. Schumpelick: Is it really justified to compare laparoscopic versus an open approach without any functional results? After a laparoscopic approach, you have a defect of the muscles covered by mesh. Sometimes there is a rectus diastasis in the midline, and in the open approach you close it. Therefore, we need a functional test of whether there are differences or not. Have you seen such a test? The story of Reeves and Flament was to close the hernia to increase the muscle stability of the abdomen. Matthews: More and more surgeons in the U.S. do not use the laparoscopic approach on every patient—and in my practice as well—because, from a functional standpoint, some patients benefit from an abdominal reconfiguration or reconstruction. Flament: I was questioned about the selection of patients. In Sevilla, Ramshaw said that hernias with loss of domain are not suitable for laparoscopic treatment. Yesterday Predeep Chowbey said we have to select our patients, as laparoscopy is not

343 Chapter 45 · Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair

suitable for every patient. If so, the biggest hernias go to open surgery, and the smaller ones maybe go to laparoscopic surgery. How can you introduce that in the analysis of the results? Matthews: If you look at the results, the actual hernia size was much bigger in the laparoscopic patients. So the selectivity, in terms of bigger ones being done open and the smaller ones laparoscopically, did not really hold out in this analysis. I think one of the things that actually really came out is that, especially in the U.S., the average BMI of a ventral hernia patient is morbidly obese—about 35—and so I have to consider that we are producing more morbidity and maybe increasing the functional outcome, or is it a good trade-off? To me, a lot of times that makes sense, and these are the discussions I actually have with the patient. We never discussed these things 5 or 6 years ago with the patient. Selectivity has become more of an issue. Fitzgibbons: Actually, we are now usually reconstructing the abdominal wall laparoscopically. I routinely now close the defects. But to do that, of course, you have to pick smaller hernias to some extent. So we are individualizing. But you have an enormous advantage of laparoscopy as you decrease the infection rate. In the right patient, it is still a very good choice. And with regard to fixation with the tacks, my goal with the tacks is to seal the polypropylene side of the prosthesis so that the bowel cannot get in contact—not so much for the fixation. Deysine: You mentioned that patients were not always operated by surgeons who were up to date with the changes that have happened. You have general surgeons doing this kind of operation, sometimes with results that are not that great. The essence of this conference should be spread to the general surgical population until this becomes a specialty. Chowbey: As I mentioned yesterday, we have to select the patients that we operate laparoscopically or by conventional surgery with anatomical repair reinforced by the mesh. And what we also emphasize is that the recurrence after open surgery is generally very small, and these small recurrences can be very easily and comfortable managed laparoscopically. That has been our policy. We treat

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the large incisional hernias by the conventional method, and when they come back with a recurrence, which is usually a small hernia recurrence, we handle it laparoscopically. That probably gives the best functional and anatomic results.

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Tissue Ingrowth, Adhesion, and Mesh Contraction S. L. Bachman, A. Ramaswamy, B. J. Ramshaw

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Chapter 46 · Tissue Ingrowth, Adhesion, and Mesh Contraction

Introduction

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As is the case with almost every medical intervention, the use of surgical prosthetics for hernia repair is a double-edged sword. While mesh has allowed for tension-free repairs and low recurrence rates, there has been a long learning curve regarding how to appropriately fabricate and use these materials. The development of complications such as fistulas, pain, mesh migration, and hernia recurrences are among the complications our patients have suffered as mesh and placement techniques continue to evolve. It has become clear that mesh materials are not inert; they both stimulate a reaction in the organism and undergo changes over time while implanted [1]. This paper examines three interactions between the body and mesh: tissue ingrowth into mesh and its effects, adhesions to mesh, and mesh contraction in vivo.

Tissue Ingrowth »Ingrowth« of a mesh refers to the interdigitation of the mesh with fibrous tissue. This was historically considered a positive property of a material, as the ingrowth of collagen (scar) incorporates the mesh into the abdominal wall. However, it is also recognized that if ingrowth occurs on the visceral surface, such as on bowel or bladder, ingrowth is a negative effect that can lead to mesh contamination and fistulas. Multiple studies have examined the ingrowth of materials in animal models; the outcome measures of these studies are varied, including histologic examinations of the tissue–mesh interface, measurements of the force required to disrupt mesh from the abdominal wall, and sophisticated imaging models. Klinge et al. have demonstrated that mesh incorporation is the result of almost pure collagenous tissue deposited around and between the mesh fibers [2]. They demonstrated an acute inflammatory response after mesh insertion that peaked at 7–14 days, with concomitant fibroblast infiltration and a slow resolution of active cells in the wound bed until 90 days postoperative, when only a physiologic cell turnover of <1% was noted [2]. This study

compared monofilament heavyweight polypropylene with lightweight multifilament polypropylene prosthetics. The heavyweight material had a more intense inflammatory response with a corresponding fibrosis. A dense plate of connective tissue completely embedded the mesh. In comparison, the lightweight polypropylene material had a less pronounced inflammatory and fibrotic response, with eventual formation of a thin scar framework and fatty tissue interspersed within the mesh pores [2]. Mesh was laparoscopically inserted onto the abdominal wall in pigs and then examined at 28 days by Jacob et al. [3]. They found that threedimensional (3D) polyester mesh took more force to be disrupted from the abdominal wall (4.15 N/ cm2) than oxidized regenerated cellulose-coated lightweight polypropylene (3.11 N/cm2) or heavyweight polypropylene (2.96 N/cm2). Histology was not quantified beyond demonstrating fibrous ingrowth between all mesh types [3]. A number of studies have looked at peel strength as a proxy for integration. A comparison in swine performed by McGinty et al. evaluated heavyweight polypropylene, coated 3D polyester, and expanded polytetrafluoroethylene (ePTFE) mesh. They found that the force of disruption was 1.3 N/cm for ePTFE, 2.1 N/cm for heavyweight polypropylene, and 2.8 N/cm for polyester [4]. Additional histology demonstrated fibrous tissue between the pores of the polypropylene and polyester weaves. There was fibrous tissue noted in the micropores of the ePTFE surface, but there was no growth through the solid ePTFE [4]. Gonzalez and Ramshaw reported on the histologic differences between flat polyester, 3D polyester, and heavyweight polypropylene meshes 25 weeks after implantation [5]. They found that fibrous encapsulation of the polypropylene was twice that of the polyester meshes, although polypropylene had less foreign body reaction than either polyester mesh. However, polypropylene had significantly less connective tissue present than the polyesters did [5]. Histology demonstrated fibrous tissue within the pores of the polypropylene and the polyester. The long-term ingrowth of mesh was studied by Novitsky at al., who examined four types of mesh placed in an intraperitoneal location in rabbits [6]. Three barrier meshes–heavyweight polypropylene/

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ePTFE composite, dual-sided ePTFE, and lightweight polypropylene/oxidized regenerated cellulose (ORC) coating–were compared with macroporous, uncoated, heavyweight polypropylene. The strength of mesh incorporation into the abdominal wall was measured by three differentiated variablereluctance transducers. No significant difference was noted between the meshes in the force required to disrupt the mesh from the tissue; however, the compliance of the surrounding tissue was significantly higher in the lightweight polypropylene [6]. Examination and measurement of the abdominal wall after implantation of mesh in humans was performed by Welty et al. [7] using ultrasound and 3D stereography. Heavyweight monofilament polypropylene mesh was compared to more elastic and lowweight meshes. The patients with the heavyweight monofilament mesh had more complaints of paresthesias and abdominal discomfort, as well as more recurrences (although not statistically significant). Three-dimensional stereography demonstrated increased stiffness of all abdomens with mesh, but the extent of the stiffness increased with mesh weight and decreased pore size [7]. These findings support the concept that a florid ingrowth around the mesh can be detrimental to a hernia repair. Thus, if the sequelae of fibrous reactions to mesh are considered more detrimental (extensive fibrosis, loss of abdominal wall compliance, pain) than beneficial, it would be helpful to understand which meshes will stimulate this reaction. An interesting study by Sanders et al. [8] took the concept beyond pore size and investigated whether the size of mesh filaments affects the overall fibrotic ingrowth. Polypropylene fibers in four diameters ranging from 2.0 μm to 27.0 μm were implanted in rat soft tissue for 5 weeks. After histology slides were obtained, the thickness of the fibrous capsule surrounding each filament was calculated. Fibers that were smaller than 6.0 μm had no encapsulation in 87% of them, and overall had significantly smaller capsules than the fibers larger than 6.0 μm [8].

Mesh Adhesions The same factors that promote ingrowth of the muscular fascia of the abdominal wall, as described

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above, are a potential problem when the mesh is exposed to the abdominal viscera. Polypropylene and polyester have been used since the 1950s [9, 10] and are two of the most frequently used types of mesh in ventral hernia repair. They are structurally macroporous and allow tissue, including chronic inflammatory tissue, to grow through the pores. Macroporous meshes have been coated with substances to place against the abdominal viscera to prevent ingrowth to bowel. However, when a microporous (or solid) barrier is lacking between the viscera and the macroporous mesh, such as when titanium is used as the coating substance, there is potential for ingrowth of bowel.

Human Studies Evidence supports the contention that macroporous mesh should not be placed into the peritoneal cavity. Halm et al. [11] showed that reoperations following intraperitoneal polypropylene mesh placement are much more difficult and dangerous than reoperations when mesh is placed outside the peritoneal cavity. There was a 76% complication rate when operating on patients with mesh previously placed in the abdominal cavity, compared to a 29% complication rate in patients who had mesh placed outside the abdominal cavity. In this retrospective study of 66 patients, all eight bowel resections and two enterocutaneous fistulas occurred in the group of patients who had mesh placed in the peritoneal cavity [11]. A common mesh used for laparoscopic ventral hernia repair is ePTFE, which is designed for intraabdominal placement with a microporous side placed toward the abdominal cavity. A retrospective review reported the findings at reoperations in patients in whom ePTFE had been placed laparoscopically for ventral hernia repair [12]. The reoperations in 65 patients showed that most patients (50/65) had adhesions to the mesh; however, the adhesions were mostly graded as easy to take down (44/50 were assigned a score of 1). It was also noted that no enterotomies occurred during lysis of adhesions [12]. Another human study evaluated postoperative adhesions using a dynamic ultrasound technique [13]. This study of 80 patients evaluated the inci-

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Chapter 46 · Tissue Ingrowth, Adhesion, and Mesh Contraction

dence of adhesion formation after open or laparoscopic ventral hernia repair using a polyester mesh with an absorbable collagen coating designed for intraperitoneal placement. Adhesions were present at 1 year in 14% of patients by ultrasound examination [13]. The incidence of intestinal ingrowth when using mesh coated with a solid microporous or hydrogel-type barrier is unknown at this time. Damage may occur during mesh manipulation or fixation with tacks or sutures, which may strip off the antiadhesive barrier and expose the macroporous material to the abdominal viscera.

⊡ Fig. 46.1. Macroporous mesh being cut off the abdominal wall but left on multiple loops of bowel due to ingrowth of bowel into macroporous mesh

Animal Studies There are numerous reports comparing mesh products placed in the abdominal cavity in animal adhesion models [4, 14–28]. Various animal models, including rat, rabbit, and pig, have been studied to look at mesh adhesions. In these animal models, mesh is placed in the abdominal cavity and fixed to the peritoneal surface of the abdominal wall. The peritoneum and/or abdominal contents, such as small bowel or cecum, are abraded to induce injury that would simulate an abdominal wall hernia repair in humans. By abrading the bowel, this injury induces adhesion formation more reliably than if no peritoneal damage were induced. Although slight differences in the specific adhesion rates for each type of mesh are observed when comparing these studies, all of the studies show that the meshes designed for intraabdominal placement (either with a solid microporous PTFE barrier or an absorbable solid barrier) result in fewer adhesions compared with macroporous meshes, including lightweight macroporous meshes. An important concept when discussing adhesions to mesh is the fact that adherence alone is not a major problem for surgeons who must reoperate on a patient with a previous mesh placement. An adhesion to mesh may rarely cause pain or bowel obstruction for the patient, but long-term complications and difficult reoperations occur if there is ingrowth of the abdominal viscera into and through the mesh (⊡ Fig. 46.1). This ingrowth of viscera can lead to the difficult and dangerous re-

operations mentioned earlier and can result in late bowel obstructions and fistulas that can harm patients (⊡ Fig. 46.2a, b). There are reports of fistulas and bowel obstructions caused by intraperitoneal placement of macroporous mesh up to 30 years after implantation [28–32]. This evidence suggests that even if macroporous mesh is no longer placed into the peritoneal cavity after today, we as surgeons will continue to face difficult reoperations and will be managing enterocutaneous fistulas and bowel obstructions due to macroporous mesh placed in the abdominal cavity for many more decades.

Mesh Contraction Surgeons who have had the occasion to remove mesh from patients will be familiar with the phenomenon of mesh contraction (⊡ Fig. 46.3a–c). The acknowledgement of mesh contraction has led to important changes in hernia repair technique. An inadequate length of extension of mesh onto healthy tissue may lead to recurrence if the mesh retracts away from the hernia. The phenomenon of mesh contraction has been documented in experimental models, such as that by Klinge et al. [33]. This canine study established that mesh contraction occurs as early as within 4 weeks after implantation. They noted that heavyweight polypropylene was reduced to 54% of its original size, and a reduced-weight polypropylene mesh was

349 Chapter 46 · Tissue Ingrowth, Adhesion, and Mesh Contraction

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a

a

b ⊡ Fig. 46.2. a A mesh designed for intraabdominal placement [heavyweight polypropylene/polytetrafluoroethylene (PTFE) composite] was used in a laparoscopic ventral hernia repair. b A stitch was placed in the center of the mesh to help position the mesh laparoscopically. The stitch apparently caused a defect in the expanded PTFE, and an enterocutaneous fistula developed a year after the operation

66% of its implantation size [33]. Many other investigators have also documented shrinkage of prosthetics in vivo. Coda et al. found that prosthetics would shrink or even expand in response to being bathed in different types of fluids [34]. Gonzalez et al. explanted mesh from swine abdominal walls 3 months postoperatively and found that the mean size of heavyweight polypropylene squares was 67% of their original size, and flat polyester mesh was 87% of its original size [35]. They also studied tissue integration and found that a higher force was necessary to distract the polyester mesh (mean 194 N) versus the polypropylene (159 N) [35].

b

c ⊡ Fig. 46.3. a A composite heavyweight/expanded polytetrafluoroethylene (ePTFE) mesh immediately after being excised from the anterior abdominal wall. Note the scalloped edges that have exposed the heavyweight component to the viscera. b An ePTFE explant after tissue has been removed. The mesh is stiff and contracted into this twisted shape. c A composite heavyweight polypropylene/ePTFE mesh after explantation and cleaning

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Chapter 46 · Tissue Ingrowth, Adhesion, and Mesh Contraction

In another swine study, early explanation at 28 days demonstrated that 3D polyester mesh was 70.5% of its original size, heavyweight polypropylene was 74.7%, and lightweight polypropylene with ORC was 66.4% of the initial size [3]. A study with 4-week explants found that heavyweight polypropylene was 94% of its original size, 3D polyester was 79%, and ePTFE was 63% of the original size [4]. At 1 year postoperative, Novitsky et al. found that ePTFE had contracted by a mean of 32.1%, ePTFE/ heavyweight polypropylene composite by 8.9%, heavyweight polypropylene by 4.6%, and lightweight polypropylene coated with ORC by 8.7% [6]. The early timeline of contraction implicates the immediate wound-healing inflammatory response as the mechanism. The initial deposition of collagen by fibroblasts and the encasement of the mesh seem to have a role. We tested this theory by administering a daily low dose of steroid to swine with three types of mesh implanted on the anterior abdominal wall. A second group of animals did not receive the injection. Mesh was explanted at 3 months. There was variable contraction between the groups, but all three types of mesh in the steroid-treated animals had 10% less contraction than the corresponding untreated mesh (manuscript in preparation). Surveying the literature on mesh contraction leads to many contradictory results: Sometimes heavyweight polypropylene contracts more, sometimes ePTFE, sometimes lightweight materials. Some researchers have hypothesized that the location of the mesh in the abdominal wall will influence contraction [36]. However, there does seem to be a trend that an increased load of foreign material will incite more inflammation and possibly contraction. An increased size of mesh pore interstices also seems to reduce scar formation. This kind of analysis is helping to drive the shift to lighter-weight, lower-density prosthetics [37–39].

Conclusion Mesh prosthetics undergo changes within the body, and they incite an inflammatory response as well. A body of research is accumulating in the literature to try to better define these effects. New mesh configurations are an attempt to minimize

the sequelae of scar plate formation around the mesh while still obtaining the ingrowth that helps secure the mesh’s position, diminish contraction, and prevent adhesions to the visceral surface of the mesh. We can expect to see more refinements of the materials used in hernia repair in the future.

References 1. Costello CR, Bachman SL, Ramshaw BJ, Grant SA (2007) Materials characterization of explanted polypropylene hernia meshes. J Biomed Mater Res B Appl Biomater 83B:44–49 2. Klinge U, Klosterhalfen B, Birkenhauer V, Junge K, Conze J, Schumpelick V (2002) Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res 103:208–14 3. Jacob BP, Hogle NJ, Durak E, Kim T, Fowler DL (2007) Tissue ingrowth and bowel adhesion formation in an animal comparative study: polypropylene versus Proceed versus Parietex Composite. Surg Endosc 21:629–33 4. McGinty JJ, Hogle NJ, McCarthy H, Fowler DL (2005) A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a porcine model using multiple types of mesh. Surg Endosc 19:786–90 5. Gonzalez R, Ramshaw BJ (2003) Comparison of tissue integration between polyester and polypropylene prostheses in the preperitoneal space. Am Surg 69:471–6; discussion 476–7 6. Novitsky YW, Harrell AG, Cristiano JA, Paton BL, Norton HJ, Peindl RD, Kercher KW, Heniford BT (2007) Comparative evaluation of adhesion formation, strength of ingrowth, and textile properties of prosthetic meshes after long-term intra-abdominal implantation in a rabbit. J Surg Res 140:6–11 7. Welty G, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick V (2001) Functional impairment and complaints following incisional hernia repair with different polypropylene meshes. Hernia 5:142–7 8. Sanders JE, Stiles CE, Hayes CL (2000) Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density. J Biomed Mater Res 52:231–7 9. Usher FC, Ochsner J, Tuttle LL, Jr. (1958) Use of marlex mesh in the repair of incisional hernias. Am Surg 24:969–74 10. Usher FC, Wallace SA (1958) Tissue reaction to plastics; a comparison of nylon, orlon, dacron, teflon, and marlex. AMA Arch Surg 76:997–9 11. Halm JA, de Wall LL, Steyerberg EW, Jeekel J, Lange JF (2007) Intraperitoneal polypropylene mesh hernia repair complicates subsequent abdominal surgery. World J Surg 31:423–9; discussion 430

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12. Koehler RH, Begos D, Berger D, Carey S, LeBlanc K, Park A, Ramshaw B, Smoot R, Voeller G (2003) Minimal adhesions to ePTFE mesh after laparoscopic ventral incisional hernia repair: reoperative findings in 65 cases. JSLS 7:335–40 13. Aube C, Pessaux P, Tuech JJ, du Plessis R, Becker P, Caron C, Arnaud JP (2004) Detection of peritoneal adhesions using ultrasound examination for the evaluation of an innovative intraperitoneal mesh. Surg Endosc 18:131–5 14. Harrell AG, Novitsky YW, Cristiano JA, Gersin KS, Norton HJ, Kercher KW, Heniford BT (2007) Prospective histologic evaluation of intra-abdominal prosthetics four months after implantation in a rabbit model. Surg Endosc 21:1170–4 15. Bellon JM, Rodriguez M, Garcia-Honduvilla N, Gomez-Gil V, Pascual G, Bujan J (2007) [Real-time monitoring of the peritoneal behavior of composite prostheses by sequential laparoscopy: applicability in ventral hernia repair]. Cir Esp 82:290–6 16. Christoforoni PM, Kim YB, Preys Z, Lay RY, Montz FJ (1996) Adhesion formation after incisional hernia repair: a randomized porcine trial. Am Surg 62:935–8 17. Alimoglu O, Akcakaya A, Sahin M, Unlu Y, Ozkan OV, Sanli E, Eryilmaz R (2003) Prevention of adhesion formations following repair of abdominal wall defects with prosthetic materials (an experimental study). Hepatogastroenterology 50:725–8 18. Matthews BD, Pratt BL, Pollinger HS, Backus CL, Kercher KW, Sing RF, Heniford BT (2003) Assessment of adhesion formation to intra-abdominal polypropylene mesh and polytetrafluoroethylene mesh. J Surg Res 114:126–32 19. Gonzalez R, Rodeheaver GT, Moody DL, Foresman PA, Ramshaw BJ (2004) Resistance to adhesion formation: a comparative study of treated and untreated mesh products placed in the abdominal cavity. Hernia 8:213–9 20. Conze J, Rosch R, Klinge U, Weiss C, Anurov M, Titkowa S, Oettinger A, Schumpelick V (2004) Polypropylene in the intra-abdominal position: influence of pore size and surface area. Hernia 8:365–72 21. Johnson EK, Hoyt CH, Dinsmore RC (2004) Abdominal wall hernia repair: a long-term comparison of Sepramesh and Dualmesh in a rabbit hernia model. Am Surg 70:657–61 22. Matthews BD, Mostafa G, Carbonell AM, Joels CS, Kercher KW, Austin C, Norton HJ, Heniford BT (2005) Evaluation of adhesion formation and host tissue response to intraabdominal polytetrafluoroethylene mesh and composite prosthetic mesh. J Surg Res 123:227–34 23. Demir U, Mihmanli M, Coskun H, Dilege E, Kalyoncu A, Altinli E, Gunduz B, Yilmaz B (2005) Comparison of prosthetic materials in incisional hernia repair. Surg Today 35:223–7 24. Kayaoglu HA, Ozkan N, Hazinedaroglu SM, Ersoy OF, Erkek AB, Koseoglu RD (2005) Comparison of adhesive properties of five different prosthetic materials used in hernioplasty. J Invest Surg 18:89–95 25. Burger JW, Halm JA, Wijsmuller AR, ten Raa S, Jeekel J (2006) Evaluation of new prosthetic meshes for ventral hernia repair. Surg Endosc 20:1320–5

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26. Harrell AG, Novitsky YW, Peindl RD, Cobb WS, Austin CE, Cristiano JA, Norton JH, Kercher KW, Heniford BT (2006) Prospective evaluation of adhesion formation and shrinkage of intra-abdominal prosthetics in a rabbit model. Am Surg 72:808-13; discussion 813–814 27. Bellon JM, Rodriguez M, Garcia-Honduvilla N, Pascual G, Gomez Gil V, Bujan J (2007) Peritoneal effects of prosthetic meshes used to repair abdominal wall defects: monitoring adhesions by sequential laparoscopy. J Laparoendosc Adv Surg Tech A 17:160–6 28. Majeski J (1998) Migration of wire mesh into the intestinal lumen causing an intestinal obstruction 30 years after repair of a ventral hernia. South Med J 91:496–8 29. Fernandez Lobato R, Martinez Santos C, Ortega Deballon P, Fradejas Lopez JM, Marin Lucas FJ, Moreno Azcoita M (2001) Colocutaneous fistula due to polypropylene mesh. Hernia 5:107–9 30. DeGuzman LJ, Nyhus LM, Yared G, Schlesinger PK (1995) Colocutaneous fistula formation following polypropylene mesh placement for repair of a ventral hernia: diagnosis by colonoscopy. Endoscopy 27:459–61 31. Losanoff JE, Richman BW, Jones JW (2002) Entero-colocutaneous fistula: a late consequence of polypropylene mesh abdominal wall repair: case report and review of the literature. Hernia 6:144–7 32. Costa D, Tomas A, Lacueva J, de Asis Perez F, Oliver I, Arroyo A, Sanchez A, Andreu J, Gallego JA, Calpena R (2004) Late enterocutaneous fistula as a complication after umbilical hernioplasty. Hernia 8:271–2 33. Klinge U, Klosterhalfen B, Muller M, Ottinger AP, Schumpelick V (1998) Shrinking of polypropylene mesh in vivo: an experimental study in dogs. Eur J Surg 164:965–9 34. Coda A, Bendavid R, Botto-Micca F, Bossotti M, Bona A (2003) Structural alterations of prosthetic meshes in humans. Hernia 7:29–34 35. Gonzalez R, Fugate K, McClusky D, 3rd, Ritter EM, Lederman A, Dillehay D, Smith CD, Ramshaw BJ (2005) Relationship between tissue ingrowth and mesh contraction. World J Surg 29:1038–43 36. Garcia-Urena MA, Vega Ruiz V, Diaz Godoy A, Baez Perea JM, Marin Gomez LM, Carnero Hernandez FJ, Velasco Garcia MA (2007) Differences in polypropylene shrinkage depending on mesh position in an experimental study. Am J Surg 193:538–42 37. Klinge U, Klosterhalfen B, Conze J, Limberg W, Obolenski B, Ottinger AP, Schumpelick V (1998) Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. Eur J Surg 164:951–60 38. Cobb WS, Kercher KW, Heniford BT (2005) The argument for lightweight polypropylene mesh in hernia repair. Surg Innov 12:63–9 39. Cobb WS, Burns JM, Peindl RD, Carbonell AM, Matthews BD, Kercher KW, Heniford BT (2006) Textile analysis of heavy weight, mid-weight, and light weight polypropylene mesh in a porcine ventral hernia model. J Surg Res 136:1–7

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Discussion Deysine: The degradation is usually secondary to

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white cell proximity. I was wondering whether, in some of the specimens that you removed, you tried to analyze the contained bacteria as the orthopedists do with their prostheses. They could not find the bacteria by normal ways. Ramshaw: That is an excellent point. There will be an accelerated amount of oxidation in infection. In the infected meshes, we have not done any evaluation of the bacteria. This is one of the things we want to look at. We also want to look at the clinical correlations from infection, chronic pain, recurrence, etc., and the patient characteristics such as smoking, diabetes, and age. All we have done is assess clinical signs of infection. Franz: I particularly liked the distinction between surface adhesion and ingrowth. With regard to biologics, if patients have a contaminated abdomen or after failed synthetics, they are not interested in another synthetic. Technique aside, do you think cross-linking is good or bad? Ramshaw: I could certainly give you the marketing point of view on it: If it’s a company without cross-linking, cross-linking is bad because you want regeneration, and the cross-linking will prevent some of that cellular ingrowth or differentiation. Companies that have cross-linking say that non-cross-linking is bad because it is a risk for early degradation. I think the answer is that we have a lot of first-generation biologics, and we really have not solved the real issue of getting those cells to come in and differentiate into the right types of material in the right patient. And that is what I think the next generation of biologics may actually be better designed to do for our patients. Klinge: You described the degradation of polypropylene. Usually, pure polypropylene is not suitable to make filaments, and there are a lot of additives and other substances which are mixed to the polypropylene. Unfortunately, we do not know what these additives are. Did you see any differences in the degradation process between the various polypropylenes? Some years ago, we saw in histological analysis that some of the propylene heavyweight meshes behaved better than expected. I believe

that there is some difference, but we do not know what happens. Ramshaw: I completely agree. Polypropylenes are not the same; there are a lot of differences in the way they are constructed; there is a high variability in the degree of degradation. Potential variables are the length of time implanted, the bacterial milieu, more degradation with infection, the different types of fibers themselves. We are going to try to look at it as we start to correlate all of the variables together in this large database.

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Effect of Different Mesh Materials on Adhesion Formation S. Morales-Conde, J. Martín-Cartes, M. Socas

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Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

Introduction

47

Because of the necessity of placing prosthetic materials to reduce the high rate of recurrence associated with conventional hernia repair without mesh, aggressive dissection of tissues occurs during conventional open repair. Laparoscopic surgery has introduced a new technique for repairing defects of the anterior abdominal wall in order to avoid this large dissection, which is associated with discomfort, the use of drains, the possibility of contamination and infection of the meshes used, and a long hospital stay for the patient. These effects have led surgeons to accept the laparoscopic approach as a valid option for our patients [1]. Laparoscopic surgery and its application in the treatment of ventral hernia have produced a change in surgeon mentality. Before the advent of this technique, surgeons always avoided placing foreign materials in contact with intraabdominal viscera in order to avoid adhesions. Laparoscopic repair of ventral hernias is associated with the use of intraabdominal prostheses. This has improved the evolution of these materials toward better ingrowth to the anterior abdominal wall, but at the same time it has reduced the possibility of creating adhesions and their potential complications, such as fistulas and bowel occlusion [2]. The ideal mesh for intraperitoneal placement has yet to be found. It should follow the principles for any prosthetic material, such as being sterilizable, noncarcinogenic, chemically inactive, and resistant to physical manipulation, and it should cause no inflammation, change in mesh characteristics, altered tissue contact, or allergic or hypersensitivity reaction. Moreover, the optimal mesh should have certain characteristics when placed intraabdominally: minimal pain and adhesion formation, excellent tissue ingrowth with minimal shrinkage, no formation of fistula or infection, and minimal seroma formation. It is also important that the prosthetic material cause no change in abdominal compliance while at the same time being easy to manipulate.

Factors Related to Adhesion Formation with Prosthetic Materials The formation of adhesions is an extremely complex process that has not yet been completely explored. As a result, many of the studies on this phenomenon are still empirical, but the results published so far are promising. It is possible that we will be able to control this process in the near future, whether stimulating or inhibiting it, depending on the circumstances. The consequence of this could be the possibility of applying these prosthetic materials for intraabdominal use in laparoscopic surgery of the abdominal wall with no risk of creating adhesions and their subsequent consequences, such as fistulas and bowel occlusion. In the meantime, while we try to determine the different factors involved in adhesion formation, the ideal materials and substances to prevent adhesions are still far from being found. Different studies performed so far have proved that it is possible to reduce the quantity and the quality of these adhesions but not to prevent them completely. Full tissue integration without adhesion formation is still a challenge in the use of intraabdominal mesh materials. Different factors have been associated with the process of adhesion formation, but the need of the bowel and intraperitoneal organs to isolate foreign agents (prosthetic materials, sutures, bacteria, etc.) seems to play an important role. However, during laparoscopic repair of ventral hernia, the presence of intraperitoneal adhesions is a result not just of the material itself; experimental studies have related adhesions to the surgical technique used. Spiral tacks, improper placement and fixing of the mesh, and exposure of the sides of these materials to the intraabdominal viscera could be related to adhesion formation [3]. We also lack information about the healing process involved in adhesion formation. It would be interesting in the future to determine the critical moment when adhesions to prosthetic materials are formed. For that reason, some authors have designed different studies using sequential laparoscopy to monitor the real-time adhesion formation process and the critical period when most adhesions form [4, 5].

355 Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

If we analyze the factors involved in adhesion formation when a mesh in placed intraperitoneally, we can determine the following: ▬ Material: Different studies [6–12] have shown that the porosity of the material is one of the most important factors related to adhesion formation and ingrowth. Large porosity has been related to an increased number of adhesions. Polypropylene mesh (PPM) is considered a high-porosity prosthetic material that creates an important scar tissue involved in adhesion formation. On the other hand, a low-porosity material, such as expanded polytetrafluoroethylene (ePTFE) [6–9, 13, 14], produces a tissue capsule that covers the mesh with a low rate of adhesions. Therefore, we can conclude that the pore size of the mesh is critical in the development and maintenance of abdominal adhesions and tissue ingrowth. It has been demonstrated, however, that reducing the amount of material and increasing the pore size result in better mesh biocompatibility, with a potential reduction of adhesion formations [15, 16], as some have tried to demonstrate with the new lower-weight PPM. These large-pore PPMs in the intraabdominal position have shown a reduced inflammatory tissue reaction, so they could be considered an alternative for the development of intraperitoneal onlay meshes [17]. In fact, new studies with reduced-weight PPM have demonstrated less change in the adjacent tissue’s pliability/ compliance and less adhesion than conventional PPM [18]. In the future, these factors should also be analyzed with regard to the pore size of other materials, such as PTFE. The larger-pore, thinner meshes such as condensed PTFE (cPTFE) have led to better tissue integration compared with the other PTFE-based meshes or PPM. Through hydrophobic chemistry, a low profile, and increased pore size, cPTFE balances the rapid resolution of the inflammatory and wound-healing response to resist adhesion formation, with efficient integration within the surrounding abdominal tissue [19]. ▬ Surgical technique for placing the mesh: An experimental study conducted by our group

47

[20] has demonstrated the influence of the surgical technique of mesh placement during laparoscopic ventral hernia repair (LVHR). In this study, most of the adhesions to the ePTFE meshes were observed at the edges, compared with the central part of this prosthetic material. The potential reasons for these adhesions were analyzed, and it could be seen how adhesions formed to the undesired exposition of the parietal face of the prosthesis or to tacks improperly introduced into the mesh. These issues demonstrate the need for a meticulous technique to avoid complications related to adhesions, such as bowel occlusion and perforation. The mesh must be properly extended so that the parietal face is not exposed to the bowel, and tacks should be introduced all the way into the mesh to avoid their hanging from the anterior abdominal wall. ▬ Fixation: As stated previously, adhesions to spiral tacks may occur, and we have observed these in experimental studies. Recent clinical papers have even reported cases of obstruction and/or perforation of the small bowel resulting from a band adhesion caused by a displaced spiral tack [21, 22]. ▬ Surgical trauma: Surgical trauma to the bowel or to the peritoneal surface of the anterior abdominal wall during the process of adhesiolysis has some influence in adhesion formation, even if the ideal intraabdominal mesh is used. Adhesions result from the normal peritoneal wound-healing response and develop during the first 5–7 days after injury. Adhesion formation and adhesion-free reepithelialization are alternative pathways. These both begin with coagulation, which initiates a cascade of events resulting in the buildup of a fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are opposed [23]. The band or bridge becomes the basis for the organization of an adhesion, especially if a foreign body reaction is added to the process when a mesh is placed intraabdominally, becoming of great importance to the surgical trauma on the bowel surface [24].

356

Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

Analysis of the Influence of Different Prosthetic Materials on Adhesion Formation

47

Many prosthetic materials to be placed intraabdominally during LVHR are available on the market, and new meshes are introduced regularly. However, experimental and clinical documentation on safety, including information on adhesions, fistulas, bowel occlusion, infection, and efficacy, are often not available to the clinician. The choice of mesh may therefore be difficult in clinical practice. Regarding adhesion formation, different experimental studies on animals show different results (⊡ Table 47.1), and a mesh superior to another in terms of adhesion formation in one study may be inferior to the same mesh in another study. If we analyze the different studies, the problem might be related to the fact that they involved different implantation techniques and were carried out in different animal models. In addition, the different factors analyzed previously–such as manipulation of the abdominal viscera, fixation technique, size of the mesh, size of the visceral face of the mesh in relation to the parietal face (overlap), and management of the abdominal wall area where the mesh is to be placed–may influence the results of the various studies, but in most cases, these factors are not even described in the text. A current review of the literature has been published regarding safety measures such as adhesions, fistulas, and infections after LVHR [25]. The only real concern based on this analysis is about using pure PPM in the intraperitoneal position. The use of intraperitoneal PPM to repair incisional hernias has been demonstrated in clinical and experimental studies to carry the risk of adhesion and damage to the intraabdominal viscera. Polypropylene is a material widely used in surgery, but because of its association with the formation of enterocutaneous fistulae and adhesions, direct contact between mesh and intestine is avoided. But, as has been analyzed previously, the use of PPM may be reevaluated based on the new studies of lightweight macropore meshes to determine whether it could influence adhe-

sion formation. This study clearly points to very few mesh-related complications after a proper mesh is placed intraperitoneally and shows that experimental studies and theoretical considerations may argue for using a covered mesh (a composite mesh or ePTFE) for LVHR in humans, although it is stressed that no human data at the moment support this. The only clinical information available in the literature based on reoperative findings concerning adhesions to prosthetic materials placed intraabdominally was published by Koehler et al. in 2003 [26]. They reported on a multi-institutional study of adhesions to implanted ePTFE mesh at reoperation in patients who had previously undergone laparoscopic incisional hernia repair done with the same mesh implantation technique. In this large series of reoperations after LVHR, no or minimal adhesion to implanted ePTFE mesh was observed in 91% of cases, and no severe cohesive adhesions were found. Regarding the two types of prosthetic materials accepted for intraabdominal placement, it is important to consider the following factors: ▬ ePTFE: Traditionally, ePTFE is one of the most widely used prosthetic materials for repairing abdominal wall defects, but it has been suggested that its behavior with respect to the reparative process may depend on its structure and that this factor should be considered to determine the capability to form adhesions. ▬ Composite materials: Composite biomaterials designed for repairing abdominal wall defects are usually composed of a reticular component and a second component, or barrier, which is laminar (absorbable or nonabsorbable) and placed in contact with the visceral peritoneum. Results on the effectiveness of these membranes covering PPM or polyester mesh are related to the membranes’ composition, but they are contradictory: Studies with PPM covered with materials such as polyglactin 910 mesh (PGM), with the aim of avoiding contact between the PPM and the intraabdominal viscera, demonstrated that the interposition of PGM did not alter adhesion formation

357 Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

[27]. On the other hand, other studies designed to evaluate how the composition of this second component affects the biological behavior of the biomaterial and the formation of adhesions have shown that physical barriers seem to induce similar adhesions, while adhesions formed to prostheses with chemical barriers can vary considerably, possibly depending on the chemical composition of the barrier [28]. Finally, the same amount of adhesion despite the presence of different protective barriers has been demonstrated with other polypropylene-based meshes [29]. In conclusion, it is difficult to make a final statement because the results of different studies are so contradictory. Whereas some studies have demonstrated the superiority of some composite meshes over ePTFE [30–33], others showed ePTFE to be related to less adhesion formation [18, 29, 34], and there are even studies in which the two types of mesh are similar [35]. The literature cannot give general recommendations for the choice of mesh based on randomized controlled trials. The final choice of mesh for LVHR will therefore typically be based on cost and the surgeon’s preference while we await further data from randomized controlled clinical trials.

Reducing Adhesion to Prosthetic Materials As already mentioned, meticulous technique is one of the most important factors involved in reducing adhesion formation: Avoid unnecessary surgical trauma on the surface of the peritoneum and the serosa of the bowel; avoid exposing the parietal face of the mesh to the abdominal cavity; and avoid letting spiral tacks hang from the mesh because of improper introduction through the prosthetic material. But because these circumstances are not usually present, due to the process of adhesiolysis or to a defect location that makes placement of the mesh or tacks difficult, alternative methods to avoid adhesion are under investigation. Efforts

47

to prevent or reduce adhesions have largely been unsuccessful, hindered by the empirical basis, the biochemical complexities of adhesiogenesis, and the lack of good predictive animal models. The two major strategies for adhesion prevention or reduction consist of adjusting surgical technique, as already proposed, and applying adjuvants. Different studies have been published that used a variety of substances to prevent adhesion formation to the prosthetic materials, with varying results. Hyaluronic acid/carboxymethylcellulose (HA/CMC) membranes have been used as an effective measure to prevent PPM-induced adhesions; taurolidine 2% solution has been proposed as a cost-effective alternative to HA/CMC membranes when a PPM is placed in direct contact with the abdominal viscera [36]; hyaluronate sodium in the form of a bioresorbant membrane has been demonstrated to significantly reduce the development of intraabdominal adhesions found after implantation of a PPM in the context of surgical hernia repair [37]; and a collagen foil has also been used to reduce adhesion formation [38]. Looking for a cost-effective alternative to reduce adhesion formation to mesh placed intraabdominally during LVHR, we have conducted studies with two substances that can guarantee good coverage of the complete surface of the mesh, even if a large prosthetic material is used [39, 40]. These two substances are fibrin glue (Tissucol; Baxter Biosurgery, Vienna, Austria) and hyaluronidase cream. Both substances were able to decrease, in an animal model, the number and quantity of adhesions with PPM and ePTFE meshes. The adhesion reduction with hyaluronidase cream is a consequence of an acceleration in the normal healing process needed to create adhesions. This factor may also influence the reduction of adhesions with fibrin glue, but it may be related to other factors, such as the mechanical barrier that the fibrin glue produces 3–5 min after its application and the capsule of new tissue created by the fibrin glue through a healing process different from the inflammatory process necessary to create an adhesion.

47

Author

Jenkins et al. [41]

Naim et al. [42]

Bellón et al. [43]

Baykal et al. [44]

Dasika and Widmann [45]

Bellón et al. [46]

Vrijland et al. [47]

Bellón et al. [48]

Bellón et al. [49]

Zieren et al. [50]

Year

1983

1993

1996

1997

1998

1999

2000

2000

2002

2002 ▼

Rats

Rabbits

Rabbits

Rats

Rabbits

Rats

Mice

Rabbits

Rats

Rats

Animal

40

14

8

44

48

47

72

24

196

N

ePTFE (DualMesh) PolyesterComposite

ePTFE (DualMesh) ePTFE (CV-4)

ePTFE (MycroMesh) ePTFE (DualMesh) ePTFE (STP) PP (Marlex)

PP PP + Vicryl PP + Fluorosoft

ePTFE (STP) PP (Marlex) PP (Prolene) Lyodura

PP Vicryl PP +Vicryl

PGA PP

PP (Marlex) ePTFE (MycroMesh)

PP + ePTFE (STP), PP + Interceed PP + Poloxamer

PP (Marlex) Vicryl ePTFE (STP) Silastic PHD PP (Marlex) + Gelfilm

Meshes

Open

Open

Open

Open

Open

Open

Open

Open

No differences

ePTFE (DualMesh)

PP + Fluorosoft

ePTFE (STP) Lyodura

Vicryl PP +Vicryl

PGA

ePTFE (Mycromesh)

PP + Interceed

Vicryl

Open

Open

Fewer adhesions

Open / lap

No differences

ePTFE (CV-4)

PP (Marlex)

PP + Vicryl

–

PP

PP

PP (Marlex)

–

PP (Marlex ) PP (Marlex) + Gelfilm

More adhesions

14 and 90 days

14 days

3 and 7 days

60 days

14, 30, 60, and 90 days

1, 2, and 3 months

5 and 14 days

14, 30, 60, and 90 days

1, 2, 4, and 8 weeks

Time

⊡ Table 47.1. Experimental studies comparing adhesion formation of different prosthetic materials (lap laparoscopic; PP polypropylene mesh; ePTFE expanded polytetrafluoroethylene; PHD glycerol-preserved human dura mater; PGA polyglycolic acid; PVDF polyvinylidene fluoride)

358 Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

Pigs

Rats

Borrazzo et al. [52]

González et al. [53]

Butler and Prieto [54]

Kayaoglu et al. [35]

Matthews et al. [29]

Demir et al. [55]

McGinty et al. [30]

Konstantinovic et al. [56]

2004

2004

2004

2005

2005

2005

2005

2005 ▼

Rats

Rabbits

Rats

Guinea pigs

Rats

Pigs

Rabbits

Matthews et al. [14]

2003

Rats

Van ’t Riet et al. [51]

2003

48

8

30

30

60

19

80

21

30

91

PP (Marlex) Surgisis

PP (Prolene) ePTFE (DualMesh) Parietex Composite

PP (Bard Mesh) Composix E/X PP (Bard Mesh) + Interceed

ePTFE (DualMesh) Composix E/X Sepramesh

PP (Surgipro) ePTFE (DualMesh) Sepramesh Vypro II Parietex Composite

PP (Prolene) PP (Prolene) + AlloDerm

PP (Parietene) Parietex Composite Parietene Composite Composix E/X Sepramesh ePTFE (DualMesh)

PP ePTFE (DualMesh) Sepramesh

ePTFE (DualMesh) PP (Marlex)

PP PP + Icodextrine Sepramesh Parietex

Open

Lap

Open

Open

Open

Open

Open

Lap

Open

Open

PP (Marlex) (30 days) Surgisis (90 days)

Parietex Composite

PP (Bard Mesh) + Interceed

ePTFE (DualMesh)

Sepramesh ePTFE (DualMesh)

PP (Prolene) + AlloDerm

Parietex Composite Parietene Composite Composix E/X ePTFE (DualMesh)

Sepramesh

ePTFE (DualMesh)

Sepramesh Parietex

PP (Parietene) Sepramesh

PP (Marlex)

PP PP + Icodextrine

30 and 90 days

28 days

14 days

1, 3, 9, and 16 weeks

4 weeks

4 weeks

21 days

28 days

1, 3, 9, and 16 weeks

7 and 30 days

Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

359

47

Rats

Burger et al. [32]

Harrell et al. [34]

Kiudelis et al. [58]

Jacob et al. [59]

Voskerician et al. [19]

2006

2006

2007

2007

2007

▼

Pigs

Dilege et al. [57]

2006

Rabbits

Rabbits

Rats

Rats

Rats

Sikkink et al. [31]

2006

Animal

Author

10

42

60

200

30

60

N

cPTFE (MotifMESH) ePTFE (DualMesh) Composix PP (Marlex) Proceed

Proceed Parietex Composite PP

PP (Prolene) Mersilene PP + Vicryl ePTFE Bard Proceed

ePTFE (DualMesh) Composix E/X Proceed PP (Marlex)

PP (Prolene) ePTFE (DualMesh) Ultrapro Timesh Sepramesh Parietex Composite Proceed Tutomesh

PP (Prolene) PP + Interceed Sepramesh

PP (Prolene) PP (Prolene) + Hyalobarrier gel PP (Prolene) + Tissucol ePTFE (DualMesh) Sepramesh Parietene Composite

Meshes

Open

Lap

Open

Sequential lap

Open

Open

Open

Open / lap

cPTFE (MotifMESH) Composix

Parietex Composite

ePTFE Bard Proceed

ePTFE (DualMesh)

Sepramesh Parietex Composite

PP + Interceed Sepramesh

Sepramesh

Fewer adhesions

47

Year

⊡ Table 47.1. Continued

PP (Marlex)

PPL

PP (Prolene) Mersilene PP + Vicryl

PP (Marlex)

PP (Prolene)

PP (Prolene)

More adhesions

1 and 3 months

28 days

30 days

16 weeks

7 and 30 days

28 days

2 months

Time

360 Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

Marcondes et al. [60]

Junge et al. [33]

Conze et al. [17]

2008

2008

2008

40

24

24

20

co-PVDF PP (Prolene)

PVDF+PP (Dyna.Mesh) Parietene Composite ePTFE (DualMesh) PP

PP (Surgipro Mesh) Sepramesh Composix E/X

Parietex Composite Sepramesh PP-PU 99

PP (Marlex) ePTFE (DualMesh) Composix E/X Proceed

Lap

No differences

PP

PP (Surgipro Mesh)

Sepramesh

PP (Marlex)

7, 21, and 90 days

30 days

28 days

3, 7, and 14 days

1 year

 Parietex Composite – Collagen-oxidized film-treated mesh (Sofradim, Trévoux, France)  Poloxamer – Triblock copolymers consisting of a central hydrophobic block of polyethylene glycol flanked by two hydrophilic blocks of polyethylene glycol  PolyesterComposite – Polyurethane-covered Dacron mesh (Braun, Melsungen, Germany)  PP (Marlex) – PP mesh (Bard, Murray Hill, NJ, USA)  PP (Surgipro) – Monofilament PP mesh (AutoSuture, Norwalk, CT, USA)  PP-PU 99 – Autodesigned prosthesis composed with a reticular PP mesh and a nonabsorbable 26-μm-thick polyurethane film  Proceed – PP–polydioxanone composite with oxidated cellulose coating (Ethicon, Somerville, NJ, USA)  Prolene – PP mesh (Ethicon, Somerville, NJ, USA)  PVDF + PP (DynaMesh) – Two-component (PP mesh and PVDF) monofilament mesh (FEG Textiltechnik, Aachen, Germany)  Seprafilm – Bioabsorbable translucent membrane composed of carboxymethylcellulose and hyaluronic acid (Genzyme, Cambridge, MA, USA)  Sepramesh – PP mesh coated on one side with a bioresorbable adhesion barrier (Seprafilm; Genzyme, Cambridge, MA, USA)  Silastic – Polydimethylsiloxane prosthesis (Dow Corning, Midland, MI, USA)  Surgipro Mesh – Single-layer PP mesh (U.S. Surgical, Norwalk, CT, USA)  Surgisis – Derived from porcine small intestine submucosa (Cook, Strombeek-Bever, Belgium)  Tissucol – Fibrin glue (Baxter Healthcare, Vienna, Austria)  Vicryl – Polyglactin 910 (Johnson & Johnson, Somerville, NJ, USA)  Vipro II – PP/polyglactin 910 composite mesh (Johnson & Johnson, Somerville, NJ, USA)

No differences

Parietene Composite

Sepramesh

Lap

Open

Parietex Composite, PPL-PU 99

ePTFE (DualMesh)

Sequential lap

Open

361

   





  

 





Rabbits

Rats

Rabbits

Rabbits

Rabbits

AlloDerm – Decellularized human dermis (LifeCell, Brachburg, NJ, USA) co-PVDF – Automanufactured mesh woven with PVDF polymer (Solvay, Brussels, Belgium) Composix – Nonwoven ePTFE (Davol, Cranston, RI, USA) Composix E/X – PP mesh sewn with PP stitching to a thin sheet of ePTFE (Davol, Bard, Murray Hill, NJ, USA) cPTFE (MotifMESH) – Nonwoven macroporous condensed PTFE (Proxy Biomedical, Galway, Ireland) ePTFE (CV-4) – Automanufactured mesh woven out of ePTFE suture thread CV-4 (Gore & Associates, Flagstaff, AZ, USA) ePTFE (DualMesh) – ePTFE (Gore & Associates, Flagstaff, AZ, USA) ePTFE (STP) – Gore-Tex Soft Tissue Patch, ePTFE with two laminar microporous surfaces (Gore & Associates, Flagstaff, AZ, USA). Fluorosoft – Fluoropassivated polyester (Sulzer Vascutek, Renfrewshire, Scotland) Gelfilm – Pharmacia & Upjohn, a subsidiary of Pharmacia, Kalamazoo, MI, USA Hyalobarrier gel – Sterile, transparent, and highly viscous gel obtained by condensation of hyaluronic acid (Fidia Advanced Biopolymers SRL, Abano Terme, Padova, Italy) Icodextrine – Iso-osmolar biodegradable –1,4-linked glucose polymer solution (Extraneal, Baxter Healthcare, Vienna, Austria) Interceed – Oxidized regenerated cellulose (Johnson & Johnson Medical, New Brunswick, NJ, USA) Lyo-dura – Lyophilized dura mater (Braun-Dexon, Barcelona, Spain) Mersilene – Polyethylene terephthalate (Johnson & Johnson, Somerville, NJ, USA) MycroMesh – ePTFE (Gore & Associates, Flagstaff, AZ, USA) Parietene Composite – PP mesh bonded on one side to a collagen-oxidized film (Sofradim, Trévoux, France)

Bellón et al. [4]

2007

   

Novitsky et al. [18]

2007

Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

47

362

Chapter 47 · Effect of Different Mesh Materials on Adhesion Formation

References

47

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27.

tion to intra-abdominal PPM and polytetrafluoroethylene mesh. J Surg Res. 2003;114(2):126–32 Schug-Pass C, Tamme C, Tannapfel A, Köckerling F. A lightweight polypropylene mesh (TiMesh) for laparoscopic intraperitoneal repair of abdominal wall hernias: comparison of biocompatibility with the DualMesh in an experimental study using the porcine model. Surg Endosc. 2006;20(3):402–9 Conze J, Rosch R, Klinge U, Weiss C, Anurov M, Titkowa S, Oettinger A, Schumpelick V. Polypropylene in the intraabdominal position: influence of pore size and surface area. Hernia. 2004;8(4):365–72 Conze J, Junge K, Weiss C, Anurov M, Oettinger A, Klinge U, Schumpelick V. New polymer for intra-abdominal meshes–PVDF copolymer. J Biomed Mater Res B Appl Biomater. 2008;87(2):321–8 Novitsky YW, Harrell AG, Cristiano JA, Paton BL, Norton HJ, Peindl RD, Kercher KW, Heniford BT. Comparative evaluation of adhesion formation, strength of ingrowth, and textile properties of prosthetic meshes after longterm intra-abdominal implantation in a rabbit. J Surg Res. 2007;140(1):6–11 Voskerician G, Rodriguez A, Gingras PH. Macroporous condensed poly(tetra fluoro-ethylene). II. In vivo effect on adhesion formation and tissue integration. J Biomed Mater Res A. 2007;82(2):426–35 Morales-Conde S, Cadet I, Morales-Méndez S. Management of mesh and sutures during laparoscopic ventral hernia repair: a lesson learned from an experimental model. In: Morales-Conde S (ed) Laparoscopic ventral hernia repair. Springer, Paris, 2003, pp 257–267 Peach G, Tan LC. Small bowel obstruction and perforation due to a displaced spiral tacker: a rare complication of laparoscopic inguinal hernia repair. Hernia. 2008;12(3):303–5 Ladurner R, Mussack T. Small bowel perforation due to protruding spiral tackers: a rare complication in laparoscopic incisional hernia repair. Surg Endosc. 2004;18(6):1001 Holmdahl L, Risberg B, Beck DE, Burns JW, Chegini N, diZerega GS, Ellis H. Adhesions: pathogenesis and prevention-panel discussion and summary. Eur J Surg Suppl. 1997;(577):56–62 Dinsmore RC, Calton WC Jr, Harvey SB, Blaney MW. Prevention of adhesions to polypropylene mesh in a traumatized bowel model. J Am Coll Surg. 2000;191(2):131–6 Eriksen JR, Gögenur I, Rosenberg J. Choice of mesh for laparoscopic ventral hernia repair. Hernia. 2007 ec;11(6):481–92 26. Koehler RH, Begos D, Berger D, Carey S, LeBlanc K, Park A, Ramshaw B, Smoot R, Voeller G. Minimal adhesions to ePTFE mesh after laparoscopic ventral incisional hernia repair: reoperative findings in 65 cases. JSLS. 2003;7(4):335–40 de Vries Reilingh TS, van Goor H, Koppe MJ, Bodegom ME, Hendriks T, Bleichrodt RP. Interposition of polyglactin mesh does not prevent adhesion formation between viscera and polypropylene mesh. J Surg Res. 2007;140(1):27–30

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28. Bellón JM, Serrano N, Rodríguez M, García-Honduvilla N, Pascual G, Buján J. Composite prostheses for the repair of abdominal wall defects: comparative study of physical and/or chemical barriers. Cir Esp. 2005;77(6):351–6 29. Matthews BD, Mostafa G, Carbonell AM, Joels CS, Kercher KW, Austin C, Norton HJ, Heniford BT. Evaluation of adhesion formation and host tissue response to intraabdominal polytetrafluoroethylene mesh and composite prosthetic mesh. J Surg Res. 2005;123(2):227–34 30. McGinty JJ, Hogle NJ, McCarthy H, Fowler DL. A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a porcine model using multiple types of mesh. Surg Endosc. 2005;19(6):786–90 31. Sikkink CJ, Vries de Reilingh TS, Malyar AW, Jansen JA, Bleichrodt RP, van Goor H. Adhesion formation and reherniation differ between meshes used for abdominal wall reconstruction. Hernia. 2006;10(3):218–22 32. Burger JW, Halm JA, Wijsmuller AR, Ten Raa S, Jeekel J. Evaluation of new prosthetic meshes for ventral hernia repair. Surg Endosc. 2006;20(8):1320–5 33. Junge K, Binnebösel M, Rosch R, Jansen M, Kämmer D, Otto J, Schumpelick V, Klinge U. Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intraabdominal placement in a rodent animal model. Surg Endosc. 2009;23(2):327–33 34. Harrell AG, Novitsky YW, Peindl RD, Cobb WS, Austin CE, Cristiano JA, Norton JH, Kercher KW, Heniford BT. Prospective evaluation of adhesion formation and shrinkage of intra-abdominal prosthetics in a rabbit model. Am Surg. 2006;72(9):808–13 35. Kayaoglu HA, Ozkan N, Hazinedaroglu SM, Ersoy OF, Erkek AB, Koseoglu RD. Comparison of adhesive properties of five different prosthetic materials used in hernioplasty. J Invest Surg. 2005;18(2):89–95 36. Erpek H, Tuncyurek P, Soyder A, Boylu S. Hyaluronic acid/ carboxymethylcellulose membrane barrier versus taurolidine for the prevention of adhesions to polypropylene mesh. Eur Surg Res. 2006;38(4):414–7 37. Kramer K, Senninger N, Herbst H, Probst W. Effective prevention of adhesions with hyaluronate. Arch Surg. 2002;137(3):278–82 38. Schönleben F, Reck T, Tannapfel A, Hohenberger W, Schneider I. Collagen foil (TissuFoil E) reduces the formation of adhesions when using polypropylene mesh for the repair of experimental abdominal wall defects. Int J Colorectal Dis. 2006;21(8):840–6 39. Martín-Cartes J, Morales-Conde S, Suárez-Grau J, LópezBernal F, Bustos-Jiménez M, Cadet-Dussort H, SocasMacías M, Alamo-Martínez J, Tutosaus-Gómez JD, Morales-Mendez S. Use of hyaluronidase cream to prevent peritoneal adhesions in laparoscopic ventral hernia repair by means of intraperitoneal mesh fixation using spiral tacks. Surg Endosc. 2008;22(3):631–4 40. Martín-Cartes JA, Morales-Conde S, Suárez-Grau JM, Bustos-Jiménez M, Cadet-Dussort JM, López-Bernal F, Morcillo-Azcárate J, Tutosaus-Gómez JD, Morales-Méndez S. Role

41.

42.

43.

44.

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51.

52.

53.

54.

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of fibrin glue in the prevention of peritoneal adhesions in ventral hernia repair. Surg Today. 2008;38(2):135–40 Jenkins SD, Klamer TW, Parteka JJ, Condon RE. A comparison of prosthetic materials used to repair abdominal wall defects. Surgery. 1983;94(2):392–8 Naim JO, Pulley D, Scanlan K, Hinshaw JR, Lanzafame RJ. Reduction of postoperative adhesions to Marlex mesh using experimental adhesion barriers in rats. J Laparoendosc Surg. 1993;3(2):187–90 Bellón JM, Buján J, Contreras LA, Carrera-San Martín A, Jurado F. Comparison of a new type of polytetrafluoroethylene patch (Mycro Mesh) and polypropylene prosthesis (Marlex) for repair of abdominal wall defects. J Am Coll Surg. 1996;183(1):11–8 Baykal A, Onat D, Rasa K, Renda N, Sayek I. Effects of polyglycolic acid and polypropylene meshes on postoperative adhesion formation in mice. World J Surg. 1997;21(6):579–82; discussion 582–3 Dasika UK, Widmann WD. Does lining polypropylene with polyglactin mesh reduce intraperitoneal adhesions? Am Surg. 1998;64(9):817–9; discussion 820 Bellón JM, Contreras LA, Pascual G, Bujan J. Neoperitoneal formation after implantation of various biomaterials for the repair of abdominal wall defects in rabbits. Eur J Surg. 1999;165(2):145–50 Vrijland WW, Bonthuis F, Steyerberg EW, Marquet RL, Jeekel J, Bonjer HJ. Peritoneal adhesions to prosthetic materials: choice of mesh for incisional hernia repair. Surg Endosc. 2000;14(10):960–3 Bellón JM, Contreras LA, Pascual G, Buján J. Evaluation of the acute scarring response to the implant of different types of biomaterial in the abdominal wall. J Mater Sci Mater Med. 2000;11(1):25–9 Bellón JM, Jurado F, García-Honduvilla N, López R, Carrera-San Martín A, Buján J. The structure of a biomaterial rather than its chemical composition modulates the repair process at the peritoneal level. Am J Surg. 2002;184(2):154–9 Zieren J, Paul M, Osei-Agyemang T, Maecker F, Müller JM. Polyurethane-covered dacron mesh versus polytetrafluoroethylene DualMesh for intraperitoneal hernia repair in rats. Surg Today. 2002;32(10):884–6 van ’t Riet M, de Vos van Steenwijk PJ, Bonthuis F, Marquet RL, Steyerberg EW, Jeekel J, Bonjer HJ. Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model. Ann Surg. 2003;237(1):123–8 Borrazzo EC, Belmont MF, Boffa D, Fowler DL. Effect of prosthetic material on adhesion formation after laparoscopic ventral hernia repair in a porcine model. Hernia. 2004;8(2):108–12 Gonzalez R, Rodeheaver GT, Moody DL, Foresman PA, Ramshaw BJ. Resistance to adhesion formation: a comparative study of treated and untreated mesh products placed in the abdominal cavity. Hernia. 2004;8(3):213–9 Butler CE, Prieto VG. Reduction of adhesions with composite AlloDerm/polypropylene mesh implants for

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abdominal wall reconstruction. Plast Reconstr Surg. 2004;114(2):464–73 Demir U, Mihmanli M, Coskun H, Dilege E, Kalyoncu A, Altinli E, Gunduz B, Yilmaz B. Comparison of prosthetic materials in incisional hernia repair. Surg Today. 2005;35(3):223–7 Konstantinovic ML, Lagae P, Zheng F, Verbeken EK, De Ridder D, Deprest JA. Comparison of host response to polypropylene and non-cross-linked porcine small intestine serosal-derived collagen implants in a rat model. BJOG. 2005;112(11):1554–60 Dilege E, Coskun H, Gunduz B, Sakiz D, Mihmanli M. Prevention of adhesion to prosthetic mesh in incisional ventral hernias: comparison of different barriers in an experimental model. Eur Surg Res. 2006;38(3):358–64 Kiudelis M, Jonciauskiene J, Deduchovas O, Radziunas A, Mickevicius A, Janciauskas D, Petrovas S, Endzinas Z, Pundzius J. Effects of different kinds of meshes on postoperative adhesion formation in the New Zealand White rabbit. Hernia. 2007;11(1):19–23 Jacob BP, Hogle NJ, Durak E, Kim T, Fowler DL. Tissue ingrowth and bowel adhesion formation in an animal comparative study: polypropylene versus Proceed versus Parietex Composite. Surg Endosc. 2007;21(4):629–33 Marcondes W, Herbella FA, Matone J, Odashiro AN, Goldenberg A. Laparoscopic evaluation of abdominal adhesions with different prosthetic meshes in rabbits. JSLS. 2008;12(1):58–61

Discussion Kukleta: Did you observe in the last study more seromas because you completely sealed the space between the mesh and the defect? Morales-Conde: The amount of glue is not even 2 cc for a 15×19 mesh. We are injecting this extra glue inside the sac. We saw a decrease of the seroma. Klinge: You mentioned that the fixation is responsible for the pain. What do you think about the importance of elasticity? Morales-Conde: You have to think about the elasticity of the mesh and of the capsule around the mesh. We do not have that data as we never measured the elasticity of the abdominal wall in the pigs. Klinge: I think it is not only the capsule, but the ePTFE without the capsule is not elastic at all. Gryska: I am glad to see you recognizing that the tackers can cause pain. Do you have experience with gluing only without tacks?

Morales-Conde: No. Schumpelick: Did you remove a large area of peri-

toneum for better mesh fixation? Morales-Conde: We have to analyze that in an-

other study.

48

Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature E. Honigsberg, D. Fowler, and B. Jacob

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Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature

Introduction

48

Laparoscopic ventral hernia repair (LVHR) is an accepted means of treating incisional and ventral hernias and has been associated with a number of benefits, including low wound infection rates, low recurrence rates, low postoperative pain rates, and short hospital length of stay [1]. However, LVHR requires the intraperitoneal placement of a mesh prosthesis, which can increase the risk of visceral adhesion formation and its sequelae [2]. In addition, there is a risk, although small, of recurrence due to improper mesh fixation resulting from inadequate technique or inadequate adherence of the mesh to the abdominal wall. Therefore, mesh used for LVHR requires two unique properties: an antiadhesive side to minimize adhesions to the viscera and a side that optimizes tissue ingrowth to minimize recurrence rates and mesh migration. The demand for this optimal two-sided prosthetic for LVHR has led to the research and development of a number of biomaterials specifically designed to optimize adhesiveness to the peritoneum while decreasing adhesion formation to viscera. The focus of this review article is to provide an updated literature review on the concept of fibrous ingrowth, also known as tissue ingrowth, as it relates to the use of two-layered mesh in LVHR. Baseline intraabdominal pressures (IAPs) have previously been studied in healthy humans using transduced pressures from transurethral bladder catheters [3]. While the mean pressure in the supine position was 1.8 mmHg, the mean pressures for sitting and standing were 16.7mmHg and 20.0 mmHg, respectively. The average pressure for a cough was 107 mmHg. These are the estimated pressures that an LVHR mesh would be exposed to after insertion. Given the wide variety of mesh products available for ventral hernia repairs, the authors hypothesized that learning these baseline IAP numbers could better direct the engineering of mesh prosthetics and could arm surgeons with the minimum benchmark pressures that a hernia repair needs to withstand to avoid recurrence. By studying the strength of tissue ingrowth into the various mesh products, we can better understand which materials can generate enough ingrowth to stand up to daily IAPs and ultimately

prevent recurrences. We can also evaluate which mesh products will not withstand normal pressures and instead will require more permanent fixation.

Physiology of Tissue Ingrowth The optimal technique for mesh fixation to minimize hernia recurrence rates remains debatable and often focuses on the types and number of sutures and tacks required [4]. In a porcine cadaver, the authors showed that the force required to disrupt a single transfascial suture was significantly greater than that required to disrupt a spiral tack (67 N vs. 28 N, p<0.001). Although the strength of a tack or a suture is interesting, the published conclusions on mesh fixation in human clinical studies usually fail to evaluate the type of mesh used and that mesh’s ability to incite tissue ingrowth from the peritoneal surface. The mesh prostheses commonly used are known to be both chemically and physically biocompatible; however, they are not inert and instead induce a multitude of host tissue responses, including tissue ingrowth, that play a major role in a successful LVHR [5]. Tissue ingrowth likely begins within hours of the establishment of contact between the mesh polymers and the peritoneal surface [5]. The initial cellular events over the first 2 days are dictated by an acute inflammatory response. Leukocytes, macrophages, and mast cells are released and activated. These inflammatory cells in turn release growth factors and cytokines. By the 3rd day, this process has lead to early angiogenesis from the preexisting host microvasculature. Angiogenesis continues with the formation of capillary buds and sprouts that grow into and around the mesh filaments. These sprouts ultimately interconnect with each other and form a well-perfused microvascular network. This neovasculature is required for the formation of granulation tissue, which in turn leads to incorporation of the mesh into native tissue. After a period of only 2 weeks, the tissue incorporation of the mesh implants continues on a path of collagen synthesis similar to that found in wound healing [5].

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Animal studies have helped show that the tissue ingrowth begins early and increases in strength over time. In a porcine laparoscopic ventral hernia model, Majercik et al. [6] demonstrated that the bulk of tissue ingrowth occurs during the first 2 weeks after a polypropylene mesh is inserted, and by 4 weeks the strength of the ingrowth has already reached a strength equivalent to 95% of the peak strength seen at 12 weeks [6]. By fixing sheets of polypropylene/expanded polytetrafluoroethylene (ePTFE) composite mesh to the abdominal walls and then harvesting them at different time intervals (2, 4, 6, and 12 weeks), the authors were able to demonstrate a peel strength of 0.83 lb at 2 weeks, 1.06 lb at 4 weeks, and 1.13 lb at 12 weeks (5 N). Histologic examination of specimens showed complete cellular infiltration into and through the entire layer of the polypropylene up to the ePTFE layer. This study, which looked at the peel strength of the polypropylene layer used in a heavyweight polypropylene/ePTFE composite mesh, concluded that the bulk of tissue ingrowth happens during the first 2 weeks after implantation. At 4 weeks, the strength then increases to a value that is equivalent to 95% of the peak strength measured at 12 weeks postimplantation. It is now well accepted that this tissue ingrowth provides long-term adhesive strength to the mesh. Interestingly, not all biomaterials are equally incorporated into native tissue by this cellular phenomenon. As early as 1995, Bellón et al. published results that compared the cellular response to, and subsequent tissue integration of, two different mesh prostheses in a rabbit model [7]. At the time, the two leading products were made of only one material and were heavyweight polypropylene and pure ePTFE. The authors suspected that the two materials incited different levels of inflammation and therefore implanted these two meshes into the anterior abdominal wall of rabbits, ensuring that each mesh was exposed to the peritoneal cavity. Necroscopy was performed at 14, 30, 60, and 90 days. Microscopically, the host tissue response differed between the ePTFE and the polypropylene. At the 2-week point, the ePTFE was encapsulated, not infiltrated, with connective tissue, whereas the polypropylene was infiltrated throughout

48

with loose scar tissue consisting mostly of macrophages. Collagen fibers and strong evidence of angiogenesis were not readily visible on the ePTFE until 2 months after implantation, and by 3 months postimplantation, the connective tissue was substantial and the cell population had stabilized, consisting of mostly fibroblasts. In contrast to the ePTFE, the polypropylene mesh demonstrated complete integration into the host tissue. The process of angiogenesis began within the first 2 weeks in the polypropylene mesh, and cells were distributed within the interstices of the mesh. The authors concluded that polypropylene incited a more intense inflammatory foreign body reaction and had superior tissue integration, and therefore that ePTFE was more suitable for implantation intraperitoneally, where it would be exposed to the viscera, and polypropylene was better suited for tissue integration [7]. After the development of two-sided (composite) mesh products, this variability of tissue integration among various mesh prostheses was again demonstrated in a laparoscopic porcine model that specifically looked at the tissue integration of the same materials (polypropylene and ePTFE) but in a two-sided mesh material [8]. By fixing sheets of pure two-sided ePTFE mesh and of a heavyweight polypropylene/ePTFE composite mesh to the abdominal wall in a porcine model, the authors were able to study the differences in the strength of tissue attachment to the two different materials. Again, the meshes were evaluated at different time intervals (2, 4, 6, and 12 weeks). The results showed that the strength of tissue ingrowth was significantly higher for the polypropylene composite graft relative to the strength of ingrowth into the pure ePTFE material at each time point. For example, at 2, 4, and 12 weeks, the mean peel strength for the ePTFE was 0.50 lb, 0.53 lb, and 0.51 lb, respectively (0.51 lb equals 2.27 N). This was significantly less (p<0.05) than the peel strength of the polypropylene at 2, 4, and 12 weeks, being 0.825 lb, 1.06 lb, and 1.12 lb, respectively (equivalent to 3.68 N, 4.70 N, and 5.0 N). The authors then looked at histology slides and found that at 2 weeks, the polypropylene component of the composite mesh was entirely infiltrated with fibroblasts and inflammatory cells,

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Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature

with collagen deposition occurring throughout the polypropylene. The macroporous abdominal wall surface of the ePTFE, however, showed no cellular penetration through the ePTFE at 2 weeks. The macropores were filled with benign-appearing tissue, but no collagen deposition had occurred. There were obvious differences in the histologic reaction and peel strengths between the different biomaterials, suggesting that tissue ingrowth and peel strength were superior for the polypropylene layer of the polypropylene/ePTFE composite mesh compared with a pure ePTFE material against the peritoneum [8]. The tissue ingrowth maturation process for the polypropylene seems to reach 74% of its maximum by 2 weeks and 95% of its maximum by 4 weeks. Thus, the strength plateaus after a 12-week period of time in animal studies; however, there may be evidence that cellular turnover continues for up to a year, and the severity of the continuing process may depend on the type of mesh implanted. This degree of inflammation produced in response to various LVHR mesh products has recently been studied using immunohistochemical testing for Ki-67, which is an accepted and established marker of cell proliferation and turnover [9]. In a rabbit study that compared tissue ingrowth analysis between a control of polypropylene and three mesh products–a heavyweight polypropylene/ePTFE composite mesh (hPP), pure ePTFE, and a reducedweight polypropylene/oxidized regenerated cellulose composite mesh (rPP)–the authors looked at results 4 months and 12 months postimplantation. They found that the hPP mesh group had significantly higher Ki-67 levels than the rPP and ePTFE groups at 4 months. At 12 months, a significant decrease in Ki-67 scores from the 4-month point was found in the rPP group only, while the hPP group maintained elevated levels of Ki-67. This interesting finding suggests that the heavyweight polypropylene-based mesh material incites an ongoing inflammatory process and scar remodeling that lasts even 1 year later. This finding was not seen with the lightweight polypropylene product or with the pure ePTFE. The way this finding would translate into a human clinical setting is unknown, but it may suggest that heavy-

weight polypropylene has relatively poor longterm biocompatibility compared with lightweight polypropylene and ePTFE. This poor biocompatibility may lead to poor mesh compliance [9]. The compliance of the mesh implants may change over time; the thicker the scar plate formation that results from the fibrous ingrowth, the less compliant the mesh may be in long-term follow-up. Without a compliant mesh prosthesis, the abdominal wall can become less pliable, and clinically this may result in physical discomfort, limitations in daily activities, and overall dissatisfaction. The group from Charlotte, North Carolina, performed a rabbit comparison study and within that study reported on mesh compliance 1 year after implantation [10]. Using a differentiated variable reluctance transducer (DVRT) that provided measurements of the axial forces required to stretch the mesh, the group reported compliance data on pure polypropylene, a composite mesh of polypropylene and ePTFE, pure ePTFE, and a composite of lightweight polypropylene and an oxidized cellulose layer. At 1 year, they showed that the compliance of the pure two-sided ePTFE mesh was superior to that of the other three meshes. Interestingly, using the same DVRT method to then analyze the peel strength of the mesh products, the group did not demonstrate a significant difference in peel strength among those four materials, although the heavyweight polypropylene/ePTFE composite trended toward having the greatest peel strength. A number of rabbit studies published by the same group showed no significant differences in tissue ingrowth among ePTFE, lightweight polypropylene composite mesh, and heavyweight polypropylene composite mesh [10–12]. This finding is not consistent with other published rabbit and porcine studies that compared the same products [8, 13], and it may be related to factors such as the type of animal model used and the method of obtaining and calculating the peel strength. In conclusion, while the polypropylene-based mesh materials show superior tissue ingrowth and superior peel strengths that may result in fewer recurrences, the long-term compliance of the material suffers, and this may have clinical sequelae yet to be discovered.

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Mesh Prostheses in Laparoscopic Ventral Hernia Repair Laparoscopic ventral hernia mesh is probably best described as a foreign body, and it therefore will be associated with a lifelong risk of potential adverse host reactions [14]. Thus, it is important to understand the different biomaterials currently available in meshes designed for placement within the abdominal cavity, along with the different reactions they incite when placed intraabdominally. In this review we will focus on polypropylene, polyester, and ePTFE, the three major materials used on the peritoneal surface of these two-layered meshes. A discussion of the newer bioabsorbable mesh materials is beyond the scope of this paper and can be found in a more detailed review [15]. In 1958, Francis Usher introduced polypropylene mesh to the field of inguinal hernia repair [16]. Since then, polypropylene has become the most frequently used mesh worldwide, and both heavyweight and lightweight polypropylene meshes are in use [15]. Polypropylene is hydrophobic and consists of a carbon backbone with alternating methyl and hydrogen groups attached to the carbon chain. It has been reported that in the long term, polypropylene may be subject to oxidation, which in time can change the compliance of the mesh material [17]. In addition to polypropylene, polyester has been widely used, and both two-dimensional (2D) and three-dimensional (3D) polyester meshes are available. Theoretically, a 3D weave provides more scaffolding for tissue ingrowth. Polyester is a hydrophilic, carbon-based polymer that forms strong fibers and, unlike polypropylene, has been shown to resist oxidation [17]. If placed extraperitoneally, either of these meshes can provide terrific tissue ingrowth; however, in LVHR the mesh must be placed intraperitoneally. Because of the significant cellular ingrowth that these meshes incite, neither polypropylene nor polyester should be used intraperitoneally, where they would be directly exposed to the surface of the bowel. Instead, ePTFE is the initial material that is safe to place against exposed bowel [15]. It consists of a long carbon chain with two side fluorine atoms per carbon. The two-sided mesh of ePTFE has a microporous surface (3 μm wide) on the visceral side and a macroporous

48

surface (>100 μm) on the peritoneal side. This macroporous surface was engineered to encourage maximal tissue ingrowth into a material originally designed to minimize inflammatory responses. The different mesh products can also be classified according to the physical properties of porosity and pore size [16]. Macroporous meshes, such as polypropylene and polyester, have pores >75 μm, whereas microporous mesh such as ePTFE has pores <10 μm in at least one dimension. The larger pore size permits infiltration by macrophages, fibroblasts, blood vessels, and collagen fibers, allowing for elimination of bacteria and rapid tissue ingrowth. Macroporous mesh quickly becomes fixed to tissue, whereas mesh with smaller pores limits cellular infiltration and subsequent tissue ingrowth [18]. A similar result was reported by Klinge et al. in a rat model [19]. They found that large-pore mesh was integrated in a loose network of perifilamentary granulomas, leading to improved integration and significantly less ongoing inflammatory response, whereas smaller-pore mesh was embedded only into granulomas, and the scar tissue bridged the whole small pore, leading to less integration and intense ongoing chronic inflammation. Their conclusions helped show the advantages of a large-pore mesh material. In addition to porosity, the structure of the biomaterial plays a key role in the tissue reaction to the prosthesis. Using a rabbit model, Bellón et al. compared pure ePTFE in a laminar configuration with a novel composite ePTFE made of the same laminar layer but sewn to a reticular, woven parietal layer made of woven ePTFE suture [20]. This allowed the authors to study ingrowth differences between laminar ePTFE and reticular (or woven) ePTFE. The results showed that after 14 days, the laminar mesh was encapsulated on its subcutaneous aspect by dense scar tissue. Fibroblasts, macrophages, and other leukocytes were present but colonized only the outer third of the ePTFE sheet. Its visceral layer was associated with a highly organized, thick neoperitoneum consisting of connective tissue arranged in an even, parallel fashion. The reticular composite mesh had a similar result for its laminar surface, but the reticular surface was embedded in dense repair tissue and demonstrated superior tissue ingrowth.

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⊡ Table 48.1. Commercially available two-layered mesh (ePTFE expanded polytetrafluoroethylene) Composite mesh

Visceral layer

Parietal layer

DualMesh (Gore)

Microporous ePTFE

Macroporous ePTFE

Proceed Surgical Mesh (Ethicon)

Oxidized, regenerated cellulose

Reduced-weight polypropylene (encapsulated with polydioxanone polymer)

Parietex Composite (Covidien)

Antiadhesive collagen (solution of oxidized bovine atelocollagen type I, polyethylene glycol, and glycerol)

Three-dimensional polyester weave

Sepramesh (Genzyme)

Cellulose (carboxymethylcellulose)

Polypropylene

C-Qur (Atrium)

Omega-3 fatty acid bioabsorbable coating

ProLite Ultra polypropylene

Composix E/X (Bard)

Microporous PTFE

Standard heavyweight polypropylene

48 Inflammatory cells extensively infiltrated the reticular mesh filaments. As expected, with the use of an Instron hydraulic-controlled tensiometer to evaluate the peel strength of the tissue ingrowth, the reticular mesh was significantly more adherent than the laminar mesh (26.75 N vs. 14.11 N, p<0.05) [20]. This finding shows that the type of weave of the material, more so than the actual material itself, is an important factor affecting tissue ingrowth strength. This discovery helped lead to the engineering of a number of other »composite« or two-sided meshes. The importance of both mesh porosity and spatial structure to tissue ingrowth led to the development of »second-generation« barrier meshes. A summary of the two-layered mesh commercially available today is provided in ⊡ Table 48.1.

Fibrous Ingrowth in Animal Models Because it is difficult to evaluate fibrous ingrowth in patients who have undergone LVHR, several studies have focused on comparing tissue ingrowth in different types of mesh prostheses in adhesiogenic rabbit or porcine laparoscopic ventral hernia models. Several studies already mentioned in this chapter compared pure two-sided ePTFE

mesh to heavyweight polypropylene/ePTFE and lightweight polypropylene/carboxymethylcellulose composite meshes. In a majority of the rabbit models, no significant difference in peel strength was found [9, 11], whereas in porcine models a significant difference in peel strength was noted, favoring the adherent strength of the heavyweight polypropylene composite [8]. Recently, 3D polyester-based composite meshes have also been used more often. One such composite mesh includes a 3D polyester parietal layer and an antiadhesive barrier made of a polyethylene glycol, glycerol, and collagen mixture on the visceral surface to prevent adhesions (Parietex Composite; Covidien, Norwalk, CT, USA). A number of animal studies are available that compare it to other leading mesh products currently in use [21–23]. In a porcine adhesiogenic laparoscopic ventral hernia model, McGinty et al. compared the 3D polyester/antiadhesive collagen composite mesh to the pure two-layered ePTFE mesh (DualMesh; Gore, Arizona), using heavyweight polypropylene as a control [21]. After laparoscopic insertion and survival for 4 weeks, the peel strength of the mesh from the abdominal wall was analyzed using a digital tensiometer and was found to be significantly less for the pure ePTFE than for the polyester/antiadhesive collagen composite mesh or the

371 Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials

pure polypropylene control (1.3 N/cm vs. 2.8 N/cm, p=0.001, vs. 2.1 N/cm, p=0.05, respectively). Histologically there was excellent fibrous growth into and through the polypropylene and the polyester component of the composite mesh. There was no tissue growth through the ePTFE. This finding supports the notion that complete tissue ingrowth can be found in a 3D polyester mesh and that this leads to superior adherence strength compared with the peel strength seen with pure two-sided ePTFE. In another study, the 3D polyester/antiadhesive collagen composite mesh was then compared to a heavyweight polypropylene/ePTFE composite mesh (heavyweight polypropylene parietal layer) [22]. The same porcine model was used. Again, a pure polypropylene mesh was used as a control. While the study reported on a number of variables, regarding the issue of tissue ingrowth as measured by the peel strength of the mesh from the abdominal wall, the authors concluded that the polyester composite product and the polypropylene composite product were not significantly different regarding abdominal wall adherence. This result suggests that a 3D polyester mesh has fibrous ingrowth properties similar to those of polypropylene mesh. In yet another prospective randomized study using the same adhesiogenic porcine model, the 3D polyester/antiadhesive collagen composite mesh was compared to Proceed, a composite mesh made of lightweight polydioxanone-polymer-encapsulated polypropylene on the peritoneal surface and oxidized regenerated cellulose as the antiadhesive barrier on the visceral surface [23]. Again, regular polypropylene was inserted as a control. After 1 month the mesh was harvested, and as part of the evaluation, peak peel strength was measured using a digital force gage tensiometer (Omega DFG51-10 microprocessor-based digital force gage). The results showed that the peel strength was significantly higher for the 3D polyester composite mesh than for the encapsulated lightweight polypropylene composite mesh (17.2 N vs. 10.7 N, respectively; p<0.002). The authors concluded that the 3D polyester composite mesh incited better tissue ingrowth than the lightweight encapsulated polypropylene composite mesh. In a rabbit animal study, Judge et al. found similar results when they compared the 3D poly-

48

ester/antiadhesive collagen composite mesh with another composite mesh of lightweight polypropylene/carboxymethylcellulose (SepraMesh; Genzyme) [24]. As part of their evaluation, they reported the strength of mesh incorporation by measuring the peel strength using an Instron 4502 tensiometer (Instron) at two time points, 1 month and 5 months. They showed that the peel strength of the 3D polyester/antiadhesive collagen composite mesh was superior to that of the lightweight polypropylene/carboxymethylcellulose composite mesh: 60.8 N vs. 42.6 N (p<0.001), respectively, at 1 month and 70.9 N vs. 31.5 N (p<0.001) at 5 months. In their rabbit model, the 3D polyester product had superior ingrowth at both time points compared with the lightweight, nonencapsulated polypropylene composite product. Interestingly, most of the published animal studies showed that the 3D polyester/antiadhesive collagen composite mesh had significantly more tissue ingrowth than the pure ePTFE and two different lightweight polypropylene products. However, the polyester composite mesh had no significant difference in peel strength compared with the heavyweight polypropylene composite product. ⊡ Table 48.2 summarizes these extrapolated peel-strength results from a select group of animal studies that reported at least 4 weeks of follow-up and also compared tissue ingrowth data between two different mesh materials. Given such terrific tissue ingrowth results for the 3D polyester composite mesh, as were also found for the heavyweight polypropylene composite mesh, one might be concerned about the long-term compliance of this material. But to date, not enough data suggest that the compliance of the polyester composite mesh changes significantly over time.

Shortcomings of the Animal Experiments It is difficult to compare the tissue ingrowth results among the different animal studies. For one, it is important to point out that the methods used to obtain the peel-strength force varied. In different studies, peel strength was obtained by either a handheld microprocessor-based digital

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Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature

⊡ Table 48.2. Extrapolated peel-strength results from a select group of animal studies (ePTFE expanded polytetrafluoroethylene; NS not significant)

48

First author

Animal model

Weeks

Mesh 1 (parietal layer)

Mesh 2 (parietal layer)

Peel strength, mesh 1

Peel strength, mesh 2

Reported p-value

McGinty [21]

Porcine

4

Pure ePTFE

Polyester composite

1.3 N/cm

2.8 N/cm

p=0.001

Duffy [22]

Porcine

4

Heavyweight Polypropylene composite

Polyester composite

5.1 N

4.8 N

NS

Jacob [23]

Porcine

4

Lightweight, coated polypropylene composite

Polyester composite

10.7 N

17.2 N

p<0.002

Iannitti [8]

Porcine

12

Pure ePTFE

Heavyweight polypropylene composite

0.51 lb (2.27 N)

1.12 lb (4.98 N)

p<0.05

Judge [24]

Rabbit

4, 20

Lightweight, uncoated polypropylene composite

Polyester composite

42.6 N, 31.5 N

60.8 N, 70.9 N

p<0.001, p<0.001

tensiometry [21–23] , a servohydraulic-controlled tensiometer made by Instron [8, 20], or a differentiated variable reluctance transducer [9]. To our knowledge, none of these peel-strength measuring methods has been validated well, nor can the reported results of each method be compared with one another. In addition to the different methods of obtaining peel strength, the studies vary in the type of animal model used. Some of the studies used a rat or rabbit model and employed an open mesh insertion technique, whereas other studies used porcine models with either an open mesh insertion or a laparoscopic mesh insertion technique. Some of these models were »adhesiogenic,« and others were not. If a mesh is inserted laparoscopically in an adhesiogenic animal model, it can be assumed that this would better represent the handling and trauma that the material would be exposed to during a human laparoscopic case. Some of the models attempted to create a more adhesiogenic environment by abrading the small bowel [21–23], while other models did not [8–12]. Finally, the length of time a mesh was left in situ before being analyzed varies among the studies.

Some studies evaluated the mesh at 1 month, and others at a number of different time points up to a year. Not shown in ⊡ Table 48.2 are the results of the North Carolina group’s many rabbit studies followed for up to a year, in which no significant difference was found in the peel strength of the various mesh products they tested [9–12]. These findings that failed to show a difference in peel strength may be attributable to factors related to the animal species used, the method of obtaining the peel strength, or the time the mesh was left in place. Further, the results may not be reflective of the behavior of the mesh in humans and are best used to compare mesh material. As mentioned earlier, the baseline IAP in humans when lying down, sitting, standing, and coughing was shown in one study to be 1.8 mmHg, 16.7 mmHg, 20.0 mmHg, and 107 mmHg, respectively [1]. While these baseline values are pressure values reported in mmHg, as shown in this chapter, most of the tensile strength data (the force required to separate, or peel, the mesh prosthetic from the tissue ingrowth formed on the peritoneal surface) are shear-force values and are reported in either pounds, newtons, or newtons per centimeter. Ac-

373 Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials

cording to standard physics conversion charts, a pressure value (such as mmHg) cannot be converted directly to or from a shear-force value (such as newtons). Instead, to our knowledge, the formula of pressure = force/area (N/m2) would need to be employed. Therefore, the data reported in most of these animal studies should be used only to relatively compare the two or three mesh products within that particular study. The data should probably not be extrapolated to make assumptions about whether those measured peel-strength forces are the same as the forces that would be required to withstand the normal IAPs of daily living.

Conclusion Armed with the knowledge of the varying levels of tissue ingrowth and peel strength of the different mesh products, the published clinical human studies showing different recurrence rates may make more sense. For instance, in a popular paper published in 2003 that summarized a very large series of laparoscopic hernia repairs, Heniford et al. reported a 4.7% recurrence rate after LVHR with a pure ePTFE material [25]. Extrapolated in the results is that approximately 20 of the 35 patients with recurrences experienced these recurrences for »unknown reasons.« It is certainly feasible that some of these reasons were related to lack of adequate tissue ingrowth through the ePTFE; more permanent fixation is often required for that type of mesh. Today, studies that neglect to comment on the mesh material and its inherent properties to incite tissue ingrowth may be overlooking an important early characteristic that reaches beyond the importance of whether to use a tack or a suture. Of course, the ability of a mesh to stay compliant over time may be just as important, if not more so; therefore, the optimal prosthetic may still be debatable. As LVHR has become an accepted means of dealing with a common surgical problem, the pursuit of an »ideal« mesh for intraperitoneal placement continues. Animal studies suggest that the different materials available today incite varying levels of tissue ingrowth, which translates into varying levels of adherence strength to the ab-

48

dominal wall. Both the 3D polyester composite product and the heavyweight/ePTFE composite product have superior adherence strengths compared to reported results for the other materials. That being stated, some evidence suggests that the heavyweight polypropylene composite products incite long-term inflammatory changes and even lose compliance over time, thus potentially changing the long-term biocompatibility of that product. Long-term compliance results following the use of the polyester composite product are yet to be reported. The development of composite meshes is based on the important physiologic phenomenon of fibrous tissue ingrowth, which is a well-described cellular reaction to the placement of a mesh prosthesis. Many different animal studies illustrate well the varying levels of tissue ingrowth and the longterm results of that tissue ingrowth on the mesh material. The ideal mesh must incite minimal adhesions on its visceral aspect while also inciting strong tissue ingrowth on its parietal surface and avoiding continuous long-term scar remodeling that may reduce its long-term biocompatibility.

References 1. Cobb WS, Kercher KW, Heniford BT (2005) Laparoscopic repair of incisional hernias. Surg Clin North Am 85:91–103 2. Leber GE, Garb JL, Alexander AI, Reed WP (1998) Longterm complications associated with prosthetic repair of incisional hernias. Arch Surg 133:378 3. Cobb WS, Burns JM, Kercher KW, Matthews BD, Norton HJ, Heniford BT (2005) Normal intraabdominal pressure in healthy adults. J Surg Res 129:231–235 4. van’t Riet M, de Vos van Steenwijk PJ, Kleinrensink GJ, Steyerberg EW, Bonjer HJ (2002) Tensile strength of mesh fixation methods in laparoscopic incisional hernia repairs. Surg Endosc 16:1713–1716 5. Laschke MW, Häufel JM, Thorlacius H, Menger MD (2005) New experimental approach to study host tissue response to surgical mesh materials in vivo. J Biomed Mater Res A 74(4):696–704 6. Majercik S, Tsikitis V, Iannitti DA (2006) Strength of tissue attachment to mesh after ventral hernia repair with synthetic composite mesh in a porcine model. Surg Endosc 20(11):1671–1674 7. Bellón JM, Buján J, Contreras L, Hernando A (1995) Integration of biomaterials implanted into abdominal wall: process of scar formation and macrophage response. Biomaterials 16(5):381–387

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Chapter 48 · Tissue Ingrowth and Laparoscopic Ventral Hernia Mesh Materials: An Updated Review of the Literature

8. Iannitti DA, Hope WW, Tsikitis V (2007) Strength of tissue attachment to composite and ePTFE grafts after ventral hernia repair. JSLS 11(4):415–421 9. Novitsky YW, Cristiano JA, Harrell AG, Newcomb W, Norton JH, Kercher KW, Heniford BT (2008) Immunohistochemical analysis of host reaction to heavyweight-, reduced-weight, and expanded polytetrafluoroethylene (ePTFE)-based meshes after short-and long-term intraabdominal implantations. Surg Endosc 22:1070–1076 10. Novitsky YW, Harrell AG, Cristiano JA, Paton BL, Norton HJ, Peindl RD, Kercher KW, Heniford BT (2007) Comparative evaluation of adhesion formation, strength of ingrowth, and textile properties of prosthetic meshes after long-term intra-abdominal implantation in a rabbit. J Surg Res 140(1):6–11 11. Matthews BD, Mostafa F, Carbonell AM, Joels CS, Kercher KW, Austin C, Norton HJ, Heniford BT (2005) Evaluation of adhesion formation and host tissue response to intraabdominal polytetrafluoroethylene mesh and composite prosthetic mesh. J Surg Res 123:227–234 12. Harrell AG, Novitsky YW, Cristiano JA, Gersin KS, Norton HJ, Kercher KW, Heniford BT (2007) Prospective histologic evaluation of intra-abdominal prosthetics four months after implantation in a rabbit model. Surg Endosc 21(7):1170–1174 13. Greenawalt KE, Butler TJ, Rowe EA, Finneral AC, Garlick DS, Burns JW (2000) Evaluation of Sepramesh biosurgical composite in a rabbit hernia model. J Surg Res 94:92 14. Schumpelick V, Klinge U (2003). Prosthetic implants for hernia repair. Br J Surg 90:1457–1458 15. Bachman S, Ramshaw B (2008) Prosthetic material in ventral hernia repair: how do I choose? Surg Clin North Am. 88(1):101–112 16. Amid PK (1997) Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia 1: 15–21 17. Costello CR, Bachman SL, Ramshaw BJ (2007) Materials characterization of explanted polypropylene hernia meshes. J Biomed Mater Res B Appl Biomater 83B(1):44–49 18. Gonzalez R, Ramshaw BJ (2003) Comparison of tissue integration between polyester and polypropylene prostheses in the preperitoneal space. Am Surg 69(6):471–476 19. Klinge U, Klosterhalfen B, Birkenhauer V, Junge K, Conze J, Schumpelick V (2002) Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res 103:208–214 20. Bellón JM, Rodríguez M, Serrano N, San-Martín AC, Buján J (2004) Improved biomechanical resistance using an expanded polytetrafluoroethylene composite-structure prosthesis. World J Surg 28(5):461–465 21. McGinty JJ, Hogle NJ, McCarthy H, Fowler DL (2005) A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a porcine model using multiple types of mesh. Surg Endosc 19(6):786–790 22. Duffy AJ, Hogle NJ, LaPerle KM, Fowler DL (2004) Comparison of two composite meshes using two fixation

devices in a porcine laparoscopic ventral hernia repair model. Hernia 8:358–364 23. Jacob BP, Hogle NJ, Durak E, Kim T, Fowler DL (2007) Tissue ingrowth and bowel adhesion formation in an animal comparative study: polypropylene versus Proceed versus Parietex Composite. Surg Endosc 21(4):629–633 24. Judge TW, Parker DM, Dinsmore RC (2007) Abdominal wall hernia repair: a comparison of Sepramesh and Parietex Composite mesh in a rabbit hernia model. J Am Coll Surg 204(2):276–281 25. Heniford BT, Park A, Ramshaw BJ, Voeller G (2003) Laparoscopic repair of ventral hernias: nine years’ experience with 850 consecutive hernias. Ann Surg 238(3):391–400

Discussion Deysine: How could you standardize the opera-

tion? Were there histologic proofs of the peritoneal defects? Jacob: No, we have no histology of the small intestine and the peritoneum. We had only the standardized adhesiolysis. Smeds: With regard to three-dimensional, is this again a question of where we locate the prosthesis? Jacob: In this product, we think that there is a difference between flat and three-dimensional meshes. Is you look at electromicroscopy, you see differences in neovascularization. Franz: You really have two studies going on within these experiments: one showing improved abdominal wall ingrowth, breaking strength, and the reduced adhesion on the peritoneal surface. Have you thought whether they are related? Or do you have an idea what the mechanism may be? Jacob: I do not think they are related. I think that the strong tissue ingrowth is a product of the material construction, perhaps even the three-dimensional quality; it clearly has a stronger adherence. Whether or not this is clinically important to reduce recurrences we do not know. The companies’ task was to come up with the ideal mesh, maximize tissue ingrowth, and minimize adhesions. So you can place the mesh intraperitoneally and feel comfortable. I really believe, at least based on these small studies, that this has done that.

49

Porosity and Adhesion in an IPOM Model J. Conze, M. Binnebösel, C. Krones

376

49

Chapter 49 · Porosity and Adhesion in an IPOM Model

As the advancing laparoscopic techniques for incisional hernia repair depend on meshes suitable for direct contact with the intestine, the search for the ideal mesh for intraabdominal placement continues. In the last decade, much effort has been put into the search for the perfect intraperitoneal onlay mesh (IPOM). The main problem in the investigation of meshes is the complexity of adhesion formation and the impossibility of measuring this in the human body without further invasive methods. Several meshes are available that provide some sort of adhesion barrier, but for each of these meshes we have found counterexamples of dense adhesions in our daily clinical routine. In an experimental rat model investigating modern meshes for IPOM repair, Junge et al. found an adhesion area of more than 20% despite the kind of adhesion barrier [4]. Meshes in the intraabdominal position must always maintain a balancing act between tissue– mesh ingrowth on the parietal side of the peritoneum and mesh protection on the visceral side of the peritoneum. To address the problem of adhesion formation, two different approaches have been followed to promote tissue ingrowth on the parietal side and to minimize the formation of intestinal adhesions on the visceral side. One idea is the use of barriers involving physicochemical pretreatment of a prosthesis, with the aim of creating an interface between the biomaterial and its areas of contact. The pioneer of this idea was Chevrel in 1982, when he placed a polyglactin mesh between the mesh and the intestine. Since then, many different materials have been introduced to reduce the adhesive potential and to optimize the fibrocollagenous ingrowth, including carboxymethylcellulose, amnion membrane, phospholipids, hyaluronic acid, collagen, and many more. The other approach is the use of a composite mesh made of several components, one of which is designed to attenuate or even abolish the adhesion formation process on the visceral side and enhance the fibrocollagenous ingrowth on the parietal side. Typical combinations of these composite meshes include polypropylene with expanded polytetrafluoroethylene (ePTFE) or polyvinylidene fluoride (PVDF).

So far, none of the available meshes can claim to be completely antiadhesive. They can only reduce the quantity and grade of adhesions without completely eliminating adhesion formation. Kapische et al. analysed the literature and concluded that there was no evidence demonstrating the superiority of any of the available meshes for intraabdominal placement [5]. The experimental models for investigations are limited and the transferability from animals to humans confined. Moreover, most animal models do not even mirror the clinical setting. These meshes are usually experimentally implanted in a fullthickness wall defect using the mesh in an inlay bridging technique. Today this technique has been abandoned because of too many complications. Another drawback is that studies often try to compare too many parameters within a single study. To investigate the significance of a single factor, such as pore size, the researchers should change only this single factor and nothing else. We have developed a standardised experimental model in the rabbit to investigate the adhesive potential of intraabdominal mesh prostheses correlated with pore size [2, 3]. To study the adhesive potential of intraabdominal meshes, it is important to reduce other possible adhesive factors as much as possible. One of the major factors is surgical trauma; therefore, the meshes were placed by a minimally invasive laparoscopic technique. The laparoscopic incisions were placed in the lower abdomen, with the mesh placed in the upper abdomen, far away from the incisions. The systematic approach was realised by always changing only one of the textile parameters in one experimental line. Textile parameters that need to be considered are the polymer (polypropylene, polyester, ePTFE, PVDF), the filament diameter, the construction (monofilament or multifilament), and the pore size (⊡ Fig. 49.1). Pore size has become one of the most important parameters in the world of lightweight, large-pore meshes, first introduced by Klinge et al. in 1996 [7]. The foreign body reaction is characterised by thickness of the perifilamental granuloma around the mesh fibre. The smaller the pore size and the more pronounced the granuloma that develops, the more likely a bridging of these neigh-

377 Chapter 49 · Porosity and Adhesion in an IPOM Model

polymer

Filament size

Tensile strength

Filament construction

Elasticity

Weight

Surface

49

Pore size

Handling

Mesh complications Adhesions

Shrinkage

Foreign body reaction

bouring granulomas will occur, leading to a scar bridging. It seems that every polymer itself has its own bridging distance, e.g. polypropylene has a bridging distance of approximately 1,000 μm. Polypropylene mesh prostheses with a pore size below 1,000 μm will inevitably lead to a complete fibrocollagenous incorporation with a strong scar plate formation. Today there is some confusion due to mixing up of the terms »lightweight mesh« and »large pore.« Not every large-pore mesh is a lightweight mesh, and not every lightweight mesh is a largepore mesh. This was well shown by Weyhe et al., who compared a heavyweight polypropylene mesh with a lightweight polypropylene mesh, observing impaired biocompatibility for the lightweight mesh due to its microporous construction [9]. A pore size smaller than 200 μm is almost watertight; above 200 μm, neovascularisation becomes possible, and only a pore size of more than 500–600 μm allows ingrowth of soft tissue. The extent of fibrocollagenous bridging has an impact of the quality of the scar and its possible tissue contraction and subsequent mesh area shrinkage. Therefore, it is no longer sufficient to reduce the description of meshes to weight alone. The pore size or, more precisely, the porosity of meshes is relevant for the biocompatibility in the host tissue. Mesh porosity can be defined as a parameter that provides the polymer-free space for tissue ingrowth. Muhl et al. have recently published a method to objectively measure the porosity of textile implants by an image analysis system, objectifying in two dimensions the pores’ structure and geometry [8]. This enables more empirical characterisation of meshes. By adding the perifilamental

⊡ Fig. 49.1. Textile parameters of synthetic meshes for hernia repair and their influence on possible complications

foreign body granuloma to the in vitro porosity of meshes, the »effective porosity« can be defined. Surgeons today must choose from more than 100 available hernia meshes. But mesh technology has become a scientific world of its own, with a terminology of its own. Many parameters have an impact on the biocompatibility. The only attempt at an internationally accepted classification of meshes was undertaken by Amid back in 1997, when the large-pore group was represented by Marlex [1]. But today the large-pore meshes have a pore size of up to 3,000 μm. Furthermore, we now have new mesh polymers, such as PVDF, with a monofilament structure but a molecular weight much higher than polypropylene–heavyweight meshes independent of the pore size. There is no longer any reason to classify meshes by their weight. What seems more important is the amount of contact area between the mesh and the host tissue surface. A multifilament mesh construction increases the mesh surface by a factor of 1.57 [6]. Enlargement of the pore size leads to a reduction in total filament length and, therefore, less mesh surface. There seems to be a correlation between pore size/surface area and adhesive potential. In our standardised IPOM rabbit model, we placed pure polypropylene meshes of three different pore sizes (0.6 mm, 2.5 mm, and 3.5mm) intraabdominally by laparoscopy. We then measured the amount of adhesion formation by planimetry and evaluated the adhesions with a specific score after 7, 21, and 90 days. We found a significant difference in the degree of adhesion area and adhesion score between the two large-pore mesh constructions and the small-pore mesh for all time points (⊡ Table 49.1).

378

Chapter 49 · Porosity and Adhesion in an IPOM Model

⊡ Table 49.1. Influence of pore size (0.6 mm, 2.5 mm, 3.5 mm) on adhesion formation after 7, 21, and 90 days in a rabbit model of laparoscopic intraperitoneal onlay mesh repair (PP polypropylene) Planimetry (mm²) n

Mean

SD

Min

Max

n

Mean

SD

Min

Max

5

1,121.7*

600.8

513.1

1,869.4

5

7.0*

2.0

5.0

9.0

21

5

1,111.8*

484.9

568.8

1,696.5

5

7.8*

1.3

6.0

9.0

90

4

869.0*

499.8

396.2

1,538.5

4

7.5*

1.3

6.0

9.0

7

5

244.2

135.4

125.1

410.4

5

3.0

0.0

3.0

3.0

21

5

351.9

190.9

45.8

565.7

5

3.0

0.0

3.0

3.0

90

5

141.6

112.0

0.0

307.1

5

2.4

1.3

0.0

3.0

7

6

479.1

343.9

84.9

1,020.5

6

4.2

1.3

3.0

6.0

21

6

306.9

294.8

14.4

835.3

6

3.8

1.0

3.

5.0

90

5

4.9

10.9

0.0

24.4

5

0.6

1.3

0.0

3.0

Material

Days

PP 0.6

7

PP 2.5

PP 3.5

Score

49 It seems obvious that we need a new terminology for modern meshes. Not all lightweight meshes are lightweight meshes! A new parameter to differentiate hernia meshes should consider the mesh surface area and the effective porosity. The influence of mesh construction (filaments, pore size, geometry) is probably more important than the polymer itself. In the experimental setting, minimal-surface, large-pore meshes have shown a reduced adhesive potential. Further studies should focus on the right balance between fibrocollagenous ingrowth and adhesion formation.

References 1.

2.

3.

4.

Amid PK (1997) Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia 1:15–21 Conze J, Junge K, Klinge U, Weiss C, Polivoda M, Oettinger AP, Schumpelick V (2005) Intraabdominal adhesion formation of polypropylene mesh. Influence of coverage of omentum and polyglactin. Surg Endosc 19:798–803 Conze J, Rosch R, Klinge U, Weiss C, Anurov M, Titkowa S, Oettinger A, Schumpelick V (2004) Polypropylene in the intra-abdominal position: influence of pore size and surface area. Hernia 8:365–372 Junge K, Binnebosel M, Rosch R, Jansen M, Kammer D, Otto J, Schumpelick V, Klinge U (2009) Adhesion forma-

5.

6.

7.

8.

9.

tion of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model. Surg Endosc 23:327–333 Kapischke M, Schulz T, Schipper T, Tensfeldt J, Caliebe A (2008) Open versus laparoscopic incisional hernia repair: something different from a meta-analysis. Surg Endosc 22:2251–2260 Klinge U, Junge K, Spellerberg B, Piroth C, Klosterhalfen B, Schumpelick V (2002) Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface, the bacteria adherence, and the in vivo consequences in a rat model. J Biomed Mater Res 63:765–771 Klinge U, Klosterhalfen B, Conze J, Limberg W, Obolenski B, Ottinger AP, Schumpelick V (1998) Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. Eur J Surg 164:951–960 Muhl T, Binnebosel M, Klinge U, Goedderz T (2008) New objective measurement to characterize the porosity of textile implants. J Biomed Mater Res B Appl Biomater 84:176–183 Weyhe D, Belyaev O, Muller C, Meurer K, Bauer KH, Papapostolou G, Uhl W (2007) Improving outcomes in hernia repair by the use of light meshes–a comparison of different implant constructions based on a critical appraisal of the literature. World J Surg 31:234–244

Discussion Deysine: I think we have not done enough investigations about the capacity of collagen to contract.

379 Chapter 49 · Porosity and Adhesion in an IPOM Model

Conze: We have some data about the correlation of foreign body reaction and shrinkage. The stronger the foreign body reaction, the more shrinkage we see. Fitzgibbons: Don’t you think the reason why people stick to ePTFE is because it has a long track record? We have all these new adhesion barrier materials now, but these materials are going to break down; we will see the same problems as with polypropylene. That is why the U.S. surgeons are reluctant to move away from ePTFE. Miserez: I have three questions: first, is there a relationship between elasticity and pore size? Second, how would monofilament polyester react? Third, is there also a maximum size of the pores? Conze: I have three answers: first, we have no idea about the in vivo elasticity but I think the pore size is of great importance. Second, again, it is just a question of pore size. Monofilament polyester with a large pore size could be a good material as well. Third, that is a wonderful question! We saw deformation and folding with 6-mm pore size in mesh modifications – that was probably too much. It depends on the memory effect of the mesh. Schumpelick: Is it justified to make a two-dimensional definition of porosity? Because we need a definition for the three-dimensional meshes. Conze: Yes, you are right.

49

50

Benefit of Lightweight and/or Titanium Meshes? C. Schug-Paß, F. Köckerling

382

Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

Introduction

50

Despite numerous experimental investigations, the search for an ideal mesh for laparoscopic intraperitoneal use still has not concluded. Numerous experiments, mainly conducted on open small animal models, have demonstrated the advantages of meshes coated with absorbable materials, among other things. But what are the characteristics of an ideal intraperitoneal mesh? If we consider technical aspects, laparoscopic handling of the mesh should be easy and safe. Meshes should have a permanent stability, but also a defined elasticity, and they should resist infection. On the parietal side, the abdominal wall flexibility should be preserved. Maximal biocompatibility–that is, good integration into the surrounding tissue, with minimal chronic inflammatory reaction–and minimal mesh shrinkage, as well as low formation of adhesions to intestinal structures, are required. We know that heavyweight meshes with a small pore size as well as polyester meshes induce a strong inflammatory reaction with scar formation and, therefore, reduction in elasticity of the abdominal wall. The development of lightweight, large-pore, and monofilament polypropylene meshes led to a reduction in chronic inflammation and minimized the amount and strength of adhesions to intestinal structures [1–3]. By comparing composite meshes in a laparoscopic pig model, McGinty et al. showed collagen-coated polyester mesh (Parietex composite) to be the best biocompatible mesh so far, with good tissue integration on one hand and only small adhesions to intestinal structures on the other hand; this mesh was compared with a heavyweight polypropylene mesh and the DualMesh prosthesis made of expanded polytetrafluoroethylene (ePTFE) for intraabdominal use [4].

Materials and Methods Technical Data on the Meshes First Experiment Two different types of mesh were implanted, all of them 10×15 cm:

1. DualMesh (Gore) is made of ePTFE. This is a membrane-like prosthesis with a smooth and a rough surface. The ePTFE meshes are traditionally used for the intraabdominal position. 2. TiMesh Light (GfE Medizintechnik) is made of a monofilament lightweight (35 g/m2) and large-pore (diameter about 1 mm) polypropylene mesh, which is titanium coated (thickness about 30 nm). This coating makes the mesh hydrophilic and easy to place in the right position.

Second Experiment Three different composite meshes, all 10×15 cm, were implanted. All meshes consisted of a basic structure made of a monofilament polypropylene material in combination with various antiadhesive components: 1. DynaMesh IPOM (Dahlhausen Medizintechnik) is a highly elastic polypropylene mesh (28% at 32 N/cm) that is interwoven with a polyvinylidene fluoride (PVDF) thread on the visceral side. Based on the manufacturer’s information, this material is endowed with antiadhesive properties. The total weight of the mesh was 108 g/m2. 2. Proceed (Ethicon) consists of a polypropylene mesh (44 g/m2) and an absorbable coating made of PDS (polydioxanone) and Interceed (cellulose), with an absorption time of around 4 months. 3. Parietene Composite (Covidien Healthcare ) is a polypropylene mesh (73 g/m2) coated with an absorbable film made of collagen, polyethylene glycol, and glycerol. This is absorbed after 2–3 weeks.

Experimental Pig Model A laparoscopic porcine model, which was officially approved in accordance with the animal protection law, was used for comparing different meshes for intraabdominal use. Six pigs in each group were operated upon. The average weight of these animals was 28 kg. Meshes were prepared with 10 1/0-ply polypropylene threads, and in the case of ePTFE, with 10 one-ply ePTFE threads. The implantation was accomplished using one 12-mm

383 Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

and two 5-mm optic trocars. Meshes were introduced into the abdominal cavity via the 12-mm trocar, positioned in the middle/upper abdomen. They were then fixed with transfascial sutures. After 3 (first experiment) or 4 months (second experiment), the animals were sacrificed. A diagnostic laparoscopy was performed. Afterwards, the whole mesh, including the surrounding tissue, was removed. Adhesion areas and the dimensions of the mesh were measured in the fresh specimen. The data were entered into the computer and submitted for planimetric analysis.

50

a

Histology Five specimens of each mesh were taken. After fixation in formaldehyde, they were prepared with different staining methods to analyse the partial volume of inflammatory cells and the proportion of macrophages, monocytes, and T-lymphocytes. The apoptotic index was determined by immunohistochemistry with the aid of in situ end-labelling. For quantification of the extent of cell proliferation, the sections were incubated with the antibody Ki67. The morphometric analysis was performed at the interface within a distance of 300 μm of the filament.

b ⊡ Fig. 50.1. Results of first experiment. a The greater omentum adhered in a discrete manner to all implants (except for one DualMesh case). b Titanium-coated meshes were in good contact with the tissue and revealed little folding

Statistics Graphic and statistical analysis was performed with the SPSS 14.0 statistical program. The results were presented as mean values and standard deviations. Statistical analysis (analysis of variance) was carried out to determine significance levels, showing statistical significance for p-values <0.05.

Results First Experiment Macroscopic Results In none of the cases did the diagnostic laparoscopy reveal adhesions to the small bowel. With the exception of one case (DualMesh), the greater

omentum adhered in a discrete manner to all implants (⊡ Fig. 50.1a). In all cases, sharp dissection was needed to separate the omentum from the mesh surface. In particular, in the group receiving DualMesh, shrinkage as a result of folding was already evident at laparoscopy and was even more evident in the explanted specimen, whereas the titanium-coated meshes were in good contact with the tissue and revealed little folding (⊡ Fig. 50.1b). On macroscopic inspection, the meshes were covered with a shiny layer in the adhesion-free areas, but the underlying layer differed in consistency on palpation. This induration was particularly seen with the PTFE implants. The morphometric evaluation of the preoperative and postoperative mesh dimensions revealed a

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Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

Planimetric data 100% Shrinkage

90%

Adhesions

80% 70% 60% 50% 40%

a

43%

30% 20% 10%

23% 20% 9%

0% TiMesh light

DualMesh

⊡ Fig. 50.2. Macroscopic results of first experiment

50 significantly smaller contact area for the DualMesh, due in the first instance to the pronounced folding of the mesh. In contrast to the titanium-coated polypropylene mesh, the remaining mesh area was almost one-half of the initial area (57.0±13.1%). The mean area of the titanium-coated mesh was 80.0±4.1% (p=0.006; ⊡ Fig. 50.2). The area of adhesions to the greater omentum was smaller for the titanium-coated polypropylene mesh–on average, 9.0±5.4%–compared with 23.2±13.8% for the DualMesh, but because of a high standard deviation, this was not significant (p=0.055; ⊡ Fig. 50.2).

Histology and Immunohistochemistry The microscopic slides showed the polypropylene meshes firmly integrated within the surrounding tissue, with only mild scar formation and formation of a neoperitoneum, with each individual fibre being surrounded by connective tissue (⊡ Fig. 50.3a). As a result, the connective tissue structures were not always uniformly arranged. No foreign body giant cells were seen in the vicinity of the meshes.

b ⊡ Fig. 50.3. Results of first experiment. a The polypropylene meshes were firmly integrated within the surrounding tissue, with only mild scar formation and formation of a neoperitoneum, with each individual fibre being surrounded by connective tissue. b The polytetrafluoroethylene meshes were embedded within scar tissue, and a strong inflammatory reaction was seen. The connective tissue fibres were mainly arranged in parallel

In the case of PTFE, the shrunken meshes were embedded within scar tissue, and a strong inflammatory reaction was seen. Owing to the small size of pores in the membrane, however, a permanent »through-growth« of connective tissue had not taken place, so there was no firm fixation to the peritoneum. Rather, the picture was of an encapsulated membrane with additional calcifications also seen. As a result of the smooth surface of the membrane, the connective tissue fibres were mainly arranged in parallel (⊡ Fig. 50.3b).

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50

Histopathologic data 40

PV (% ) Ki 67 30

29.2

AI (% ) 20.3

20

14 10

9.3

7.5

a

3.3 0 TiMesh light

DualMesh

⊡ Fig. 50.4. Histopathologic results of first experiment (PV partial volume of inflammatory cells; AI apoptotic index)

With regard to the partial volume of the inflammatory cells, the median figures were lowest for TiMesh Light (20.3±2.1%) and were significantly higher for DualMesh (29.2±5.5%, p=0.009; ⊡ Fig. 50.4). Investigations with the proliferation marker Ki67, a sign of cell activity, again showed the highest figures for DualMesh (14.0±3.9%), which were thus also significantly higher than for TiMesh (7.5±3.3%, p=0.011; ⊡ Fig. 50.4). Finally, evaluation of the apoptotic index as a sign of cell turnover with consecutive cell death again revealed the highest figures for the ePTFE membranes. The figure here was 9.3±2.5%, which was again significantly higher than for the titaniumcoated polypropylene meshes (3.3±2.7%, p=0.002; ⊡ Fig. 50.4).

Second Experiment

b

c ⊡ Fig. 50.5a–c. Results of second experiment. More or less widespread adhesions to the greater omentum were noted for all meshes; these were often seen around the mesh margins

Macroscopic Results In no case did laparoscopic diagnosis show any adhesions to the intestinal structures, but these were seen in some cases to the parenchymatous organs depending on the position of the mesh

and its contact with the liver and spleen. More or less widespread adhesions to the greater omentum were noted for all meshes. These were often seen around the mesh margins (⊡ Fig. 50.5a–c).

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Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

Adhesions 25.0%

DualMesh TiMesh light 9.0%

Parietene Composite 12.8% 33.2%

DynaMesh

31.6%

Proceed ⊡ Fig. 50.6. Results of second experiment: adhesions

0%

20%

40%

80%

60%

100%

Mesh surface at explantation DualMesh

57.0%

TiMesh light

80.0%

Parietene Composite

86.0%

DynaMesh

85.0%

50 Proceed

⊡ Fig. 50.7. Results of second experiment: mesh surface at explantation

A reflecting surface, attesting to an intact neoperitoneum, was observed in those areas of the fullwall specimens that did not harbour any adhesions. Only by resorting to sharp dissection was it possible to detach, in particular, the greater omentum in areas with adhesions. The density of adhesions did not differ among the meshes. Parietene Composite had the fewest adhesions. Planimetric analysis revealed a 12.8±9% adhesion surface to the greater omentum for Parietene Composite. As such, this was markedly less than that evidenced by Proceed, but this finding was not significant (31.7±18.5%, p=0.06). Compared with DynaMesh IPOM, there was a significant difference (33.2±11.9%, p=0.01; ⊡ Fig. 50.6). There was no evidence of any major folding in any of the meshes on macroscopic inves-

75.0%

0%

20%

40%

60%

80%

100%

tigation. The greatest reduction in mesh surface was seen with Proceed (25.0±7.5%). This shrinkage was significantly higher than in DynaMesh IPOM (14.2±7.1%, p=0.03) and was likewise significantly higher than in Parietene Composite (14.0±8.6%, p=0.04), which produced comparable values (⊡ Fig. 50.7). The results are summarised in ⊡ Table 50.1. All meshes were completely integrated into the abdominal wall.

Histology and Immunohistochemistry Histology showed only minor signs of a chronic inflammatory reaction. The polypropylene meshes were all well integrated into the surrounding tissue. Formation of the neoperitoneum was complete in the adhesion-free areas (⊡ Fig. 50.8a–c).

387 Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

a

50

4.5±2.7%, than for Proceed (10.8±5.7%, p=0.04) and were markedly, but not significantly, lower than for DynaMesh IPOM (7.2±6.7%, p=0.4). The apoptotic index, as a marker of cell death, was very low for all meshes, and no significant differences were seen (DynaMesh IPOM 1.2±0.4%, Proceed 1.5±0.8%, Parietene Composite 1.7±0.8%; ⊡ Fig. 50.9). Overall, Parietene Composite scored best in the macroscopic as well as the histologic investigations. In terms of shrinkage of the mesh surface, the DynaMesh IPOM and Parietene Composite meshes scored equally well and were superior to Proceed. Findings are summarised in ⊡ Table 50.1.

Discussion

b

c ⊡ Fig. 50.8a–c. Results of second experiment. The polypropylene meshes were all well integrated into the surrounding tissue. Formation of the neoperitoneum was complete in the adhesion-free areas

The partial volume of inflammatory cells showed the lowest values for Parietene Composite. With a value of 6.6±2.9%, this was significantly lower than for Proceed, at 14.7±4.6% (p=0.006), or for DynaMesh IPOM, at 19.7±7.8% (p=0.007). The Ki67-positive cells in a proliferation stage were also significantly lower for Parietene Composite, at

Numerous publications, including those of an experimental nature, concentrate mainly on the extent and pathology of adhesions. In this regard, polypropylene meshes have proven to be considerably inferior to ePTFE meshes. In our study we were able to show that the lightweight and large-pore TiMesh Light is associated with fewer adhesions than ePTFE mesh, and in no cases were intestinal adhesions seen. This confirms that the structure of the material employed is of decisive importance for this phenomenon. The reduction in material and increase in pore size represent a considerable improvement over the original heavier polypropylene mesh [1, 3, 5–7]. The adhesions of the intestine to the mesh described in other publications [8–10] were not seen in our experiments. A major factor here is certainly the minimally invasive placement of the mesh and the lack of previous adhesiolysis or injury of the peritoneum. Adhesion reactions include that of the tissue to foreign material, which, in the case of intraperitoneal meshplasty, takes place at the peritoneum–mesh interface. As also borne out by our series of experiments, the collagen-coated mesh has performed very well in all tests. In most cases, Parietex Composite mesh (with polyester) was used [4, 11–14], and in some cases Parietene Composite mesh (with polypropylene) was used [14–17]. Proceed showed a higher rate of adhesions. However, the cellulose-based coating, albeit in

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Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

⊡ Table 50.1 Dynamesh IPOM

Proceed

Parietene Composite

Shrinkage rate (%)

14.2±7.1 (p=0.029 vs. Proceed)

25.0±7.5

14.0±8.6 (p=0.041 vs. Proceed)

Adhesion rate of the greater omentum (%)

33.2±11.9

31.7±18.6

12.8±9.9 (p=0.01 vs. Dynamesh)

Partial volume of inflammatory cells (%)

19.7±7.8

14.7±4.6

6.5±2.9 (p=0.007 vs. Dynamesh) (p=0.006 vs. Proceed)

Proliferation Ki67 (%)

7.2±6.7

10.8±5.7

4.5±2.7 (p=0.04 vs. Proceed)

Apoptotic index (%)

1.2±0.4

1.5±0.8

1.7±0.8

Macrophages/monocytes activity (CD 68)

12.5±2.2

5.5±2.9 (p=0.001 vs. Dynamesh)

3.8±2.2 (p<0.001 vs. Dynamesh)

Extracellular matrix TGF-ß

55.8±35.2

37.4±22.4

20.8±8.8

30

50

25

20

PV (%)

15

Ki67 (%) AI (%)

10

5 ⊡ Fig. 50.9. Histopathologic results of second experiment (PV partial volume of inflammatory cells; AI apoptotic index)

0 DualMesh

TiMesh light

combination with hyaluronic acid (Sepramesh), appears to confer advantages in principle, as attested to by some experimental studies [14, 16, 18–23]. It is possible that the combination with the slowly absorbable PDS (polydioxanone) plays a role because degradation of the material over a 3–4-month period provokes an acute inflammatory reaction. However, by that stage, these

Parietene Composite

DynaMesh

Proceed

differences are reflected at a cellular level only in terms of the partial volume of the inflammatory cells. Apart from that, no significant differences were seen between Proceed and Parietene Composite regarding the chronic inflammatory reaction. The adhesion rate of DynaMesh IPOM was on a par with that of Proceed. The widespread

389 Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

chronic inflammation no doubt played a role here. To what extent this is also determined by the surface structure (i.e. porous structure) or the amount of material used is something that can be conjectured only from other experimental findings [24, 25]. Greater attention needs to be paid to the effect of shrinkage. The pathophysiological reactions involved in this phenomenon are extremely complex, with shrinkage of the material being the last link in the body’s chain of reactions to the foreign material. This reaction appears to be clearly related to the site of mesh placement and also to the amount and structure of the material [2, 26–28]. This would also explain the observation that, over the long term, polypropylene mesh, fixed in an identical manner, shows considerably less tendency to shrink than does ePTFE. These reactions appear to persist over a period of years, as Klinge et al. were able to show in explanted meshes [2, 27]. Because PTFE is not really a mesh, but rather a membrane, it cannot be completely integrated despite the texturing of the surface in contact with the abdominal wall. The presence of pores in the mesh makes it possible for the individual mesh fibres to become incorporated within the process of neoperitoneum formation. In contrast, a capsule formed around the foreign material is consolidated by the chronic inflammatory reaction that occurs. The cellular reaction induced by the material is considerably greater in the case of implanted membranes in comparison with lightweight structured meshes, as we were able to demonstrate by examining the partial volume of the inflammatory cells. Increased inflammatory activity is accompanied by an increase in cell proliferation. During the course of this process, cell death (apoptosis) also rises, which is reflected in an increase in the apoptosis index. All three factors were significantly elevated with the ePTFE membrane. For the titanium-coated mesh, the average shrinkage in the intraperitoneal position was only 18%, in contrast to 43% for the DualMesh. In our second experiment, apart from Parietene Composite, DynaMesh IPOM showed the lowest shrinkage rate despite the fact that the re-

50

maining inflammatory parameters, including the adhesion rate, were markedly higher than those of Proceed or Parietene Composite. Presumably this is attributable to the mesh’s very good elasticity, which counteracts a shrinkage reaction. As expected, mesh integration into the abdominal wall was assured thanks to the textile structure of the polypropylene material used in all meshes, in the absence of any major chronic inflammatory reaction. Through-growth of the individual polypropylene fibres confers a high degree of fixation strength, which is preserved even after reduction of the polypropylene material.

Conclusions On the basis of our results, we must conclude that the titanium-coated polypropylene mesh is suitable for laparoscopic intraperitoneal repair of abdominal wall and incisional hernias and that it is comparable to DualMesh with regard to adhesions but is clearly superior in terms of shrinkage. So over the long term, it is likely to be associated with a reduction in recurrence rates. The collagen coating of the polypropylene mesh appears to confer important advantages in terms of biocompatibility, with implications for the adhesion and shrinkage profiles of the mesh material. No doubt, improvements can still be made regarding handling, composition of the coating, and tendency towards infection. Further research and experimental investigations, as well as prospective randomised clinical trials, are thus needed.

References 1. Klinge U, Conze J, Klosterhalfen B, Limberg W, Obolenski B, Ottinger AP, Schumpelick V. Changes in abdominal wall mechanics after mesh implantation. Experimental changes in mesh stability. Langenbeck’s Arch Surg 1996; 381:323–332 2. Klinge U, Klosterhalfen B, Birkenhauer V, Junge K, Conze J, Schumpelick V. Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res 2002; 103:208–214 3. Conze J, Rosch R, Klinge U, Weiss, C, Anurov M, Titkowa S, Oettinger A, Schumpelick V. Polypropylene in the intra-

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abdominal position: influence of pore-size and surface area. Hernia 2004; 8:365–372 McGinty JJ, Hogle NJ, McCarthy H, Fowler DL. A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a porcine model using multiple types of mesh. Surg Endosc 2005; 19:786–790 Scheidbach H, Tamme C, Tannapfel A, Lippert H, Köckerling F. In vivo studies comparing the biocompatibility of various polypropylene meshes and their handling properties during endoscopic total extraperitoneal (TEP) patchplasty. Surg Endosc 2004; 18:211–220 Schug-Paß C, Tamme C, Tannapfel A, Köckerling F. A lightweight polypropylene mesh (TiMesh) for laparoscopic intraperitoneal repair of abdominal wall hernias–comparison of biocompatibility with the DualMesh in an experimental study using the porcine model. Surg Endosc 2006; 20:402–409 Schug-Paß C, Sommerer F, Tannapfel A, Lippert H, Köckerling F. Does the additional application of a polylactide film (SurgiWrap) to a lightweight mesh (TiMesh) reduce adhesions in laparoscopic intraperitoneal implantation procedures? Experimental results obtained in the laparoscopic porcine model. Surg Endosc 2008; 22:2433–2439 Baptista ML, Bonsack ME, Felemovicius I, Delaney JP. Abdominal adhesions to prosthetic mesh evaluated by laparoscopy and electron microscopy. J Am Coll Surg 2000; 190:271–280 Bellon JM, Contreras LA, Pascual G, Bujan J. Neoperitoneal formation after implantation of various biomaterials for the repair of abdominal wall defects in rabbits. Eur J Surg 1999; 165:145–150 Matthews BD, Pratt BL, Pollinger HS, Backus CL, Kercher KW, Sing RF, Heniford BT. Assessment of adhesion formation to intra-abdominal polypropylene mesh and polytetrafluoroethylene mesh. J Surg Res 2003; 114:126–132 Bellon JM, Garcia-Carranza A, Jurado F, Garcia-Honduvilla N, Carrera-San Martin A, Bujan J. Peritoneal regeneration after implant of composite prosthesis in the abdominal wall. World J Surg 2001; 25:147–152 Bellon JM, Garcia-Honduvilla N, Jurado F ,Garcia-Carranza A, Garcia-Moreno F, Martin AC, Bujan J. Use of composite prostheses in the repair of defects in abdominal wall: prosthetic behaviour at the peritoneum. Eur J Surg 2001; 167:666–671 Bellon JM, Jurado F, Garcia-Honduvilla N, Lopez R, Carrera-San Martin A, Bujan J. The structure of a biomaterial rather than its chemical composition modulates the repair process at the peritoneal level. Am J Surg 2002; 184:154–159 Gonzalez R, Rodeheaver GT, Moody DL, Foresman PA, Ramshaw BJ. Resistance to adhesion formation: a comparative study of treated and untreated mesh products placed in abdominal cavity. Hernia 2004; 8:213–219 McGinty JJ, Hogle NJ, McCarthy H, Fowler DL. A comparative study of adhesion formation and abdominal wall ingrowth after laparoscopic ventral hernia repair in a

16.

17.

18.

19.

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24.

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26.

27.

28.

porcine model using multiple types of mesh. Surg Endosc 2005; 19:786–790 Schug-Paß C, Sommerer F, Tannapfel A, Lippert H, Köckerling F. The use of composite meshes in laparoscopic repair of abdominal wall hernias–are there differences in biocompatibility? Experimental results obtained in a laparoscopic porcine model. Surg Endosc 2009; 23:487– 495 Sikkink CJJM, Vries de Reilingh TS, Malyar AW, Jansen JA, Bleichrodt RP, van Goor H. Adhesion formation and reherniation differ between meshes used for abdominal wall reconstruction. Hernia 2006; 10:218–222 van´t Riet M, Burger WA, Bonthuis F, Jeekel J, Bonjer HJ. Prevention of adhesion formation to polypropylene mesh by collagen coating: a randomized controlled study in a rat model of ventral hernia repair. Surg Endosc 2004; 18:681–685 Alimoglu O, Akcakaya A, Sahin M, Unlu Y, Ozkan OV, Sanli E, Erylmaz R. Prevention of adhesion formations following repair of abdominal wall defects with prosthetic materials (an experimental study). Hepatogastroenterology 2001; 50:725–728 Besim H, Yalcin Y, Hamamci O, Arslan K, Sonisik M, Korkmaz A, Erdogan S. Prevention of intraabdominal adhesions produced by polypropylene mesh. Eur Surg Res 2002; 34:239–243 Burger JW, Halm JA, Wijsmuller AR, ten Raa S, Jeekel J. Evaluation of new prosthetic meshes for ventral hernia repair. Surg Endosc 2006; 20:1320–1325 Dilege E, Coskun H, Gunduz B, Sakiz D, Mihmanli M. Prevention of adhesion to prosthetic mesh in incisional ventral hernias: comparison of different barriers in an experimental model. Eur Surg Res 2006; 38:358–364 Felemovicius I, Bonsack ME, Hagerman G, Delaney JP. Prevention of adhesions to polypropylene mesh. J Am Coll Surg 2004; 198:543–548 Kayaoglu HA, Ozkan N, Hazinedaroglu SM, Ersoy OF, Erkek AB, Koseoglu RD. Comparison of adhesive properties of five different prosthetic materials used in hernioplasty. J Invest Surg 2005; 18:89–95 Bellon JM, Rodriguez M, Garcia-Honduvilla N, Pascual G, Bujan J. Partially absorbable meshes for hernia repair offer advantages over nonabsorbable meshes. Am J Surg 2007; 194:68–74 Weyhe D, Belyaev O, Müller C, Meurer K, Bauer KH, Papapostou G, Uhl W. Improving outcomes in hernia repair by the use of light meshes–a comparison of different implant constructions based on a critical appraisal of the literature. Word J Surg 2007; 31:234–244 Klinge U, Klosterhalfen B, Müller M, Ottinger AP, Schumpelick V (1998) Shrinking of polypropylene mesh in vivo: an experimental study in dogs. Eur J Surg 1998; 164:965– 959 Klinge U, Klosterhalfen B, Müller M, Schumpelick V. Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 1999; 165:665–673

391 Chapter 50 · Benefit of Lightweight and/or Titanium Meshes?

Discussion Amid: Adhesion formation is not as important as

what the intestine adheres to. Formation of intestinal fistula is something very slow; the longest reported period was 15 years. Now the decision of which meshes to use depends on the adhesive property. But what matters is what the bowel adheres to. Schug-Paß: In our experiment, we did not violate the peritoneum. There were only adhesions to the omentum and not to the intestine. We think that if there is a neoperitoneum formation that covers the meshes, there is no problem. Kukleta: The mesh that you chose as the best one was the first mesh that I used. But I left it because of the number of adhesions in patients that I had to reoperate. And if it is even covered with neoperitoneum, you cannot prevent adhesions with it. Deysine: Is this a thin film of titanium on the mesh? Schug-Paß: It is a special technique invented by GFE. The coating of the lightweight meshes makes no difference, but it might be different with heavy meshes. One advantage is that the titanium coating makes the polypropylene hydrophilic and thus easier to handle. Desine: I thought polypropylene was hydrophilic on its own. Schug-Paß: No.

50

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ePTFE Prostheses and Modifications G. Pascual, J. M. Bellón

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Chapter 51 · ePTFE Prostheses and Modifications

Introduction

51

Expanded polytetrafluoroethylene (ePTFE) is a microporous, laminar, hydrophobic prosthetic material with a negative charge. It is composed of compact nodules interlinked by fine fibers. The length of these fibers determines the material’s internodal distance and pore size. The first report of the use of polytetrafluoroethylene for the repair of abdominal wall defects was that by Harrison in 1957 [1], whose results were certainly promising. However, the performance of this material in woven form as a prosthesis was so disappointing [2] that its clinical use was soon abandoned. A few years later, in 1963, Oshige [3] described a method of expanding polytetrafluoroethylene, preserving its microstructure and increasing its mechanical resistance. This process was refined by Gore [4] and applied in the manufacturing of vascular prostheses for clinical use. This was followed by further significant expansion to provide a layered material that could be used to repair hernias and other soft tissue defects. The first of these prostheses used to repair parietal defects in the abdomen was the Soft Tissue Patch (STP). The behavior of ePTFE in the repair of abdominal wall defects was initially studied in the laboratory. The works of Elliot and Juler in 1979 [5] revealed the good biological tolerance of this material, and Sher et al. [6], in 1980, were the first to describe its superior peritoneal behavior compared with polypropylene. This finding was highlighted by Lamb et al. [7], who observed that the inflammatory response to an ePTFE implant was minimal. Subsequent experimental studies [8–11] confirmed the favorable behavior of the ePTFE patch at the peritoneal interface. Taking advantage of this particular behavior, Walker et al. [12] were the first to elaborate a composite prosthesis in which polypropylene was combined with a layer of ePTFE on the peritoneum-facing side of the implant. Using similar composites, good results were reported in experimental studies conducted by other authors [13, 14] and even in clinical practice [15]. The work of Bauer et al. [16] introduced the use of ePTFE in clinical hernia repair in the form of the STP, although in earlier publications [17, 18]

the advantageous behavior of ePTFE had already been described. These authors [16] reported that in 28 operated patients, this material induced a good tissue response as well as a minimal inflammatory response and infiltration of fibroblasts and collagen in the interstices of the prosthesis. At 10.7%, their hernia recurrence rate was comparable to those quoted later by other authors [19–22]. In a clinical study of patients with incisional hernias, Van der Lei et al. [23] described the need for prosthetic overlap of the tissue defect and a double suture to fix the prosthesis to avoid reherniation. In addition, as had been described by others in experimental studies, the favorable behavior of STP at the peritoneal level was indicated. In subsequent clinical trials [24, 25], this property of ePTFE was confirmed and was soon to prompt the use of STP in the laparoscopic approach to hernia repair. A property of the ePTFE patch that we should discuss is its behavior in the presence of infection. The studies by Law and Ellis [26] demonstrated that other materials, such as polypropylene, showed better tolerance to infection than ePTFE did. These findings were corroborated by other authors [27–30]. In clinical practice, it is generally accepted that ePTFE is more prone to infection than other biomaterials and that when infection occurs, most ePTFE implants will need to be removed [31, 32].

Structural Changes Suffered by ePTFE Prostheses The lack of good tissue incorporation [33] and a sometimes considerable hernia recurrence rate induced the first modifications to this prosthetic material. The first of these was the introduction of multiple perforations in the ePTFE patch in an effort to achieve a prosthesis that, although still laminar in structure, would have the properties of a reticular mesh. The initial idea of converting the STP into a macroporous prosthesis belonged to Simmermacher et al. [11], who made multiple perforations in an ePTFE prosthesis to improve tissue ingrowth. These authors even tried to modify the prosthetic structure by pretreating the ePTFE with ethanol to increase its porosity. They observed no

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gain in mechanical strength attributable to such modifications. Despite this, these experiments led to the first modification of ePTFE in the form of a prosthesis called MycroMesh (MM). In an experimental study in our laboratory [34], we observed no biomechanical benefits of the new MM over conventional ePTFE in the form of a patch (STP). Further, because of its lack of surface smoothness due to the presence of multiple orifices, greater adhesion formation was induced when it was implanted over the peritoneum. A further modification to the ePTFE patch was the creation of a prosthesis with some sort of barrier on its peritoneal side to prevent cell infiltration. This prosthesis was given the commercial name of DualMesh (DM). Further studies by our group [35] indicated the practically identical behavior of this new prosthesis to that of the classic ePTFE patches. Although there was no cell ingrowth on one of its sides, this did not seem to affect its behavior at the peritoneal interface, and its mesothelialization and neoperitoneum formation were similar to observations of STP. Furthermore, no changes were noted in mechanical strength after implantation. A final modification to DM took the form of the Corduroy type, for which a rough surface was created on its non-peritoneal-facing side. The objective was to improve tissue incorporation. However, studies by our group (unpublished results) indicated that tissue infiltration with the Corduroy mesh was similar to that for the other ePTFE prostheses, with no improvement in mechanical resistance compared with previous designs.

Modifications Involving Pretreatments Infection of a prosthetic material continues to be a significant problem in clinical practice. Given the generally poor tolerance of ePTFE to infection, determined by its microstructure, one of the innovations applied to ePTFE prostheses was their pretreatment with substances that would inhibit bacterial colonization during the initial moments of implantation and thus prevent biofilm formation. This gave rise to modified prostheses with bactericidal activity: MycroMesh Plus and DualM-

51

esh Plus. The antimicrobial agents used for pretreatment were silver carbonate and chlorhexidine diacetate. Harrell et al. [36] recently demonstrated the in vitro efficiency of these pretreatments.

Personal Experience with Experimental and Clinical ePTFE Implants Our experimental and clinical findings using a New Zealand White rabbit implant model have been as follows. Macroscopic observations at the tissue–tissue interface reveal that ePTFE becomes encapsulated such that the mesh is enveloped by an organized connective tissue to form a »sandwich.« When the implant makes contact with the visceral peritoneum, correct mesothelialization occurs from the first moments of implantation. Despite the different modifications to the layer of ePTFE, its macroscopic behavior fails to vary. On microscopic observation, tissue incorporation is preferentially cellular. STP and DM show similar behavior in that host cells are able to penetrate as far as one-third of the mesh thickness. In STP, this occurs on both surfaces; in DM, only one surface is affected. Neoperitoneum formation is similar for both prostheses, and observations include the presence of mesothelial cells and a well-organized peritoneum. Using the MM variant, tissue ingrowth proceeds via the orifices created in the prosthesis such that tissue bridges may be observed between the two prosthetic surfaces, with the existence of cellular integration as well. Unlike STP and DM, the MM mesh induces angiogenesis in the perforation zones. For the rough-surface variant of DM, incorporation continues to be cellular, with tissue deposited between the rough zones of the ePTFE surface (⊡ Fig. 51.1). On the peritoneal-facing side, adhesion formation is almost null, and when it occurs, as sometimes observed with MM, these adhesions are very loose (⊡ Fig. 51.2). An important feature to consider is the foreign body reaction induced by the biomaterial. With the use of a monoclonal antibody specific for rab-

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51 ⊡ Fig. 51.1. Macroscopic appearance of the different prostheses tested (left). Diagrams (middle) and microscopic examinations (right) of the implants showing tissue incorporation of the biomaterials 30 days after implantation. Both surfaces of the Soft Tissue Patch (STP) implant have become encapsulated by host connective tissue. Cell colonization is detectable on both prosthetic surfaces. Scar tissue surrounds the MycroMesh (MM) implant on both the peritoneal-facing and subcutaneous-tissue-facing sides. The arrows indicate the neoformed tissue within the prosthetic MM perforations. In both MM and STP, cells penetrate beyond one-third of the mesh thickness. Microscopic observation of the DualMesh (DM) and DM Corduroy implants indicates no major differences with respect to the other implants; the only differences noted are the lack of fibrous colonization of the nonporous DM surface (PS peritoneal side; SS subcutaneous side)

bit, macrophage counts were always the same for all of the prostheses. These counts were higher at the early implantation stage and thereafter underwent a steady decrease (⊡ Fig. 51.3). The mechanical strength of the different prostheses (STP, MM, DM, and DM Corduroy) failed to differ significantly (⊡ Fig. 51.4). Thus, questions arise regarding whether this similar tissue ingrowth induced by the ePTFE and all its modified forms depends on the chemical composition, and whether it can be modulated.

As already demonstrated by Amid et al. [13] using other materials, when the spatial structure of a prosthesis changes, its tissue behavior varies despite its unchanged composition. In a prosthetic design in which we used ePTFE suture thread (Cv4) to construct a mesh [37], the mesh’s behavior was similar to that of a reticular-type mesh. Moreover, its mechanical behavior postimplantation varied appreciably to attain tensile strength values comparable to those of a polypropylene prosthesis. This design revealed the different tissue

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⊡ Fig. 51.2. Macroscopic images of adhesion formation to the different prostheses. The percentage of adhesion formation is greater for the MycroMesh (MM) prosthesis than for the other three (Soft Tissue Patch, DualMesh, and DualMesh Corduroy) prostheses. Adhesions appear in areas corresponding to the suture and perforations of the MM implant. Most of these adhesions are very loose in consistency

Macrophage number

50 40 30 20 10 0 14 days

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⊡ Fig. 51.3. Number of macrophage cells recorded for the different expanded polytetrafluoroethylene prostheses implanted in the abdominal wall of New Zealand White rabbits for 14–90 days

incorporation of laminar relative to reticular-type materials. Another problem mentioned earlier is the issue of prosthetic infection. In a model of experimental infection, we were able to observe ultrastructural

⊡ Fig. 51.4. Postimplantation tensile strengths of the different prostheses. Resistance to traction increased steadily, reaching significance with respect to initial values 30–90 days after implantation of the different prostheses. These values are similar for the different types of expanded polytetrafluoroethylene prostheses at the same study times

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changes in ePTFE induced by bacterial contamination. The microbes penetrated the interstitial zones of the prostheses, where they settled. We observed changes in internode fibers and in zones of anchorage to host tissue. In clinical practice (1997), the behavior of the ePTFE implants proved to be similar to that shown experimentally. The same occurred in cases of prosthetic infection. In most cases of infection, the prosthesis must be replaced. We have no experience with the use of pretreated ePTFE (MM Plus/DM Plus), although the in vitro studies described above have yielded promising results in settings of infection.

Conclusions

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1. No modifications made to the earliest laminar ePTFE prosthesis, or Soft Tissue Patch, have resulted in any changes or improvement in tissue incorporation or postimplantation biomechanical strength. 2. Only changes in the spatial architecture of a biomaterial will alter the pattern of tissue incorporation and biomechanical strength. 3. When confronted with infection, ePTFE and its variants respond in the same susceptible way, with the exception of the pretreated prostheses.

References 1. Harrison JH. A Teflon weave for replacing tissue defects. Surg Gynecol Obstet 1957; 104:584–590 2. Gibson LD, Stafford CE. Synthetic mesh repair of abdominal wall defects: follow up and reappraisal. Am Surg 1964; 30:481–486 3. Oshige S. Japanese patent no. 42-13560 (67/13560), 1967 4. Gore RW. Process for producing porous products. U.S. patent 3953566, WL Gore and Associates, 27 April 1976 5. Elliot M, Juler GL. Comparison of Marlex mesh and microporous Teflon sheets when used for hernia repair in the experimental animal. Am J Surg 1979; 137:342–345 6. Sher W, Pollack D, Paulides CA, Matsumoto T. Repair of abdominal wall defects: Gore-Tex vs Marlex graft. Am Surg 1980; 110:618–623 7. Lamb JP, Vitale T, Kaminsky DL. Comparative evaluation of synthetic meshes used for abdominal wall replacement. Surgery 1983; 93:643–648

8. Murphy JL, Freeman JB, Dionne PG. Comparison of Marlex and Gore-Tex to repair abdominal wall defects in the rat. Can J Surg 1989; 32:244–247 9. Pans A, Pierard GE. A comparison of intraperitoneal prostheses for the repair of abdominal muscular wall defects in rats. Eur Surg Res 1992; 24:54–60 10. Le Blanc KA. Two-phase in vivo comparison study of adhesion formation of the Gore-Tex soft tissue patch, Marlex mesh and Surgipro using a rabbit model. In: Arregui ME, Nagan RF. Inguinal hernia, advances and controversies. Radcliffe Medical Press, Oxford, 1994, pp 501–504 11. Simmermacher RKJ, Van der Lei B, Schakenraad JM, Bleichrodt RP. Improved tissue ingrowth and anchorage of expanded polytetrafluoroethylene by perforation: an experimental study in the rat. Biomaterials 1991; 12:22–24 12. Walker AP, Henderson J, Condon RE. Double-layer prostheses for repair of abdominal wall defects in a rabbit model. J Surg Res 1993; 55:32–37 13. Amid PK, Shulman AG, Lichtenstein IL, Sostrin S, Young J, Hakakha M. Experimental evaluation of a new composite mesh with the selective property of incorporation to the abdominal wall without adhering the intestines. J Biomed Mat Res 1994; 28:373–375 14. Bellón JM, Buján J, Contreras L, Jurado F. Use of non-porous polytetrafluoroethylene prostheses in combination with polypropylene prosthetic abdominal wall implants in prevention of peritoneal adhesions. J Biomed Mat Res 1997; 38:197–202 15. Bendavid R. Composite mesh (polypropylene–ePTFE) in the intraperitoneal position: a report of 30 cases. Hernia 1997; 1:5–8 16. Bauer JJ, Salky BA, Gelernt LM, Kreel I. Repair of large abdominal wall defects with expanded polytetrafluoroethylene (PTFE). Ann Surg 1987; 206:765–769 17. Hamer-Hodges DW, Scott NB. Replacement of an abdominal wall defect using expanded PTFE sheet (Gore-Tex). J R Coll Surg Edinb 1985; 30:65–67 18. Wool NL, Straus AK, Roseman DL. Clinical experience with the Gore-Tex soft tissue patch in hernia repair: a preliminary report. Proc Inst Med Chir 1985; 38:33–37 19. Pailler JL, Manaa J, Vicq PH, Brissiaud JC, Gandon F. Cure des hernies de l´aine avec interposition d´une prothèse de PTFE. Lettre Chirurgicale 1987; 55:13–15 20. Pailler JL, Essoussi H, De Calan L. Eventration post-operatoire: les protheses. Moniteur Hospitalier 1990; 27:1–4 21. Kluger Y, Katz E, Ayalon A, Durst A. Repair of large abdominal wall defects with expanded polytetrafluoroethylene. Harefuah 1989; 117:292–295 22. Law NW, Ellis H. Preliminary results for the repair of difficult recurrent inguinal hernias using expanded PTFE patch. Acta Chir Scand 1990; 156:609–612 23. Van der Lei B, Bleichrodt RP, Simmermacher RKJ, Schifgaarde R. Expanded polytetrafluoroethylene patch for the repair of large abdominal wall defects. Br J Surg 1989; 76:803–805 24. Bellón JM, Contreras LA, Sabater C, Buján J. Pathologic and clinical aspects of repair of large incisional hernias af-

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25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

ter implant of a polytetrafluoroethylene prosthesis. World J Surg 1997; 21:402–407 Utrera-González A, De la Portilla F, Carranza-Albarrán G. Large incisional hernia repair using intraperitoneal placement of expanded polytetrafluoroethylene. Am J Surg 1999; 177:291–293 Law NW, Ellis H. A comparison of polypropylene mesh and expanded polytetrafluoroethylene patch and polyglycolic acid mesh for the repair of experimental abdominal wall defects. Acta Chir Scand 1990; 156:759–762 Bleichrodt RP, Simmermacher RJK, Van der Lei B, Shakenraad JM. Expanded polytetrafluoroethylene patch versus polypropylene mesh for the repair of contaminated of the abdominal wall. Surg Gynecol Obstet 1993; 176:18–24 Bellón JM, Contreras LA, Buján J. Ultrastructural alterations of polytetrafluoroethylene prostheses implanted in abdominal wall provoked by infection: clinical and experimental study. World J Surg 2000; 24:528–532 Bellón JM, García-Honduvilla N, Jurado F, García-Carranza A, Buján J. In vitro interaction of bacteria with polypropylene/PTFE prostheses. Biomaterials 2001; 22: 2021–2024 Bellón JM, García-Carranza A, García-Honduvilla N, Carrera-San Martin, Buján J. Tissue integration and biomechanical behaviour of contaminated experimental polypropylene and expanded polytetrafluoroethylene implants. Br J Surg 2004; 91:489–494 Leber GE, Garb JL, Alexander AI, Reed WP. Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 1998; 133:378–382 Taylor SG, O’Dwyer PJ. Chronic groin sepsis following tension-free inguinal hernioplasty. Br J Surg 1999; 169:397– 399 Simmernmacher RKJ, Shakenraad JM, Bleichrodt RP. Reherniation after repair of the abdominal wall with expanded polytetrafluoroethylene. J Am Coll Surg 1994; 178:613–616 Bellón JM, Buján J, Contreras LA, Carrera-San Martín A, Jurado F. Comparison of a new type of polytetrafluoroethylene patch (Mycro Mesh) and polypropylene prosthesis (Marlex) for repair of abdominal wall defects. J Am Coll Surg 1996; 183:11–18 Bellón JM, Contreras LA, Buján J, Carrera-San Martín A. The use of biomaterials in the repair of abdominal wall defects: a comparative study between polypropylene meshes (Marlex) and a new polytetrafluoroethylene prosthesis (Dual Mesh). J Biomater Appl 1997; 12:121–135 Harrell AG, Novitsky YW, Kercher KW, Foster M, Burns JM, Kuwada TS, Heniford BT. In vitro infectability of prosthetic mesh by methicillin-resistant Staphylococcus aureus. Hernia 2006; 10:120–124 Bellón JM, Jurado F, García-Honduvilla N, López R, Carrera-San Martín A, Buján J. The structure of a biomaterial rather than its chemical composition modulates the repair process at the peritoneal level. Am J Surg 2002; 184:154–159

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52

The Role of Stem Cells in Abdominal Wall Repair M. G. Franz

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Introduction

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Incisional hernias fundamentally result from acute laparotomy wound failure. Evidence supports the mechanism that gaps in the early laparotomy repair progress to clinical incisional hernias [1, 2]. The linea alba is especially at risk for acute wound failure because of the low number of repair fibroblasts and relative ischemia at this location of the abdominal wall. Laparotomy wound-healing failure occurs when there is (1) reduced quantity or 2) impaired quality of collagen matrix synthesis, recellularization, and, ultimately, tissue repair [3]. Surgical and mechanical approaches to the problem of incisional hernia formation and repair may underestimate how the biological response to injured tissue affects wound-healing outcomes. Surgical wound-healing failure is defined at the tissue, cellular, and molecular levels. A major normal mechanism is fibroblast activation from quiescence and progression of the repair cell cycle after injury [3]. It is unknown whether wound failure of the abdominal wall results from a primary inherited defect in fascial fibroblast activation leading to incisional hernia formation or, conversely, from an abnormal wound milieu after mechanical fascial wound failure that induces impaired fibroblast function [3]. A combination of the two may exist. One strategy to improve acute wound healing and decrease surgical wound failure is the pharmacological use of cytokine growth factors, which increase skin incision strength and decrease the incidence of incisional hernias in experimental models [4–7]. In vivo growth factor therapy, however, is limited by short half-lives. Another strategy is cell-based therapy. Stem cells and stem-cell-like multipotent cells express the ability to differentiate into different cell types that are important for wound healing and tissue repair [8–10]. Stem cells also secrete growth factors that signal parallel cellular processes active during wound healing. The sensor capability of cell sources of tissue repair signals may result in more physiologic healing through signal combination and dose [9–11]. Amnion-derived cells express characteristics of stem cells, including the ability to differentiate into distinct cell types of varied tissue lineages [12, 13]. Amnion-derived cells also secrete cytokines

and growth factors in culture and are reported to be nonimmunogenic [14–17]. Stem cell therapy of abdominal wall wounds may therefore accelerate and improve the gain in laparotomy breaking strength and, in so doing, decrease the incidence and severity of surgical wound failure and incisional hernia formation.

Materials and Methods AMP and GFP-labeled AMP Cells Amnion-derived multipotent progenitor (AMP) cells and AMP cells labeled with green fluorescent protein (AMP-GFP) were provided by Stemnion (Pittsburgh, PA, USA). Amnion cells were isolated from placentas following cesarean section and were processed by proprietary techniques.

Animal Model The rat models of laparotomy healing and incisional hernias have been previously described [18–20]. Sprague–Dawley rats weighing 450 g were acclimated and housed under standard conditions. All animal care and operative procedures were performed in accordance with the United States Public Health Service Guide for the Care of Laboratory Animals and were approved by the University of Michigan Committee on the Use and Care of Animals.

Laparotomy Wound-Healing Model Briefly, a ventral skin flap was raised through the avascular prefascial plane, and a 5-cm laparotomy incision was made through the linea alba. The laparotomy was repaired with a running 4-0 polypropylene suture. The skin flap was securely sutured. Two groups were studied: (1) abdominal walls treated with normal saline (NS) as the control (NS-S control) and (2) abdominal walls treated with NS-washed, human-amnion-derived multipotent progenitor cells (AMP-S group). In the NS-S group, the midline of the abdominal wall

403 Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

(linea alba) was injected over 5 cm with 200 μl of NS. In the AMP-S group, 200 μl of NS containing 106 amnion epithelial cells was similarly injected. Surgical-site priming was performed with a 22-g hypodermic needle (0.7×38 mm) into the linea alba. Soft tissue distribution of NS or AMP cell suspension was achieved. After 5 min, the laparotomy incision was made and repaired as described above. On postoperative days (PODs) 7, 14, and 28, the rats were killed. Isolated abdominal wall muscle and tendon strips and fresh biopsies of the abdominal wall to the laparotomy wound-healing interface were collected for mechanical and histological testing.

Laparotomy Wound Breaking Strength and Mechanical Properties Mechanical testing was done on abdominal wall strips collected from the laparotomy woundhealing model as previously reported [4, 19, 20]. Briefly, sutures were removed. Abdominal wall strips were made perpendicular to the woundhealing interface. A cutting template was used to mark the abdominal wall to minimize the size variability among specimens. Strips were cut 10 mm in width and 60–80 mm in length. Two strips were collected from each rat, and testing was performed within 6 h of necropsy. The thickness of the fascial tissue strip at the wound and the length between grips were measured with Digimatic calipers. Force extension curves were generated for each fascial strip with the use of an Instron tensiometer equipped with a 50-N static load cell set at a crosshead speed of 10 mm/min. The fascial strips were mounted into the load frame with the use of pneumatic grips, preloaded to 0.1 N with a gauge length between the grips of around 10 mm. The load frame applied testing loads to the fascial strips until mechanical tissue disruption occurred. Force and tissue deformation data were simultaneously recorded and captured on a computer connected to the load frame via a digital interface card. Data analysis was performed with the use of the Merlin materials testing software package (Instron, Canton, MA, USA). Breaking strength, the maximum load force (Fmax) at mechanical failure (N); tensile strength, the maximum stress developed in the

52

specimen per unit area, calculated as Fmax/crosssectional area (N/mm2); energy at break (mJ); yield strength (N); yield energy (mJ); and stiffness, the slope of the linear elastic region of the forceextension curve (N/mm), were generated.

Incisional Hernia Model Incisional hernia models were used as previously described [18, 20]. Again, a skin flap was raised, and a 5-cm laparotomy incision was made through the linea alba. To induce hernia formation, two fast-absorbing 5-0 plain gut stitches were placed at the cranial extent and midpoint of the laparotomy incision. The skin flap was again secured. Groups treated with NS (NS-H control) and human-amnion-derived multipotent progenitor cells (AMP-H) were again used for this experiment. In the NS-H control group, 200 μl of NS was injected along the midline for 5 cm. In the AMP-H group, 200 μl of NS containing 1.5×106 amnion epithelial cells was injected along the linea alba for 5 cm. On POD 28, the rats were killed, and the musculotendinous layer of the abdominal wall was collected and examined for incisional hernias.

Measurement of Hernia Size For hernia size measurement, hernia model rats were killed on POD 28. The skin was dissected free circumferentially, and a 5×10-cm section of the abdominal wall muscle was excised. The muscle was stretched out and pinned down on a dissecting board at the four corners with the peritoneal side up. A standardized digital picture was taken. Software Spot version 4.5 for Windows was used to calculate hernia size on digital pictures. Calibration was set up using the rule reference on each picture. A circle was drawn along the hernia ring to measure the hernia size in square centimeters.

Laparotomy and Incisional Hernia Histology Laparotomy wound or hernia sections were cut and fixed in formalin for histology. Specimens were stained with hematoxylin and eosin or trichrome.

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Viable AMP-GFP cells were also injected into the linea alba as described above. These tissues were embedded in O.C.T. compound and snap-frozen immediately in liquid nitrogen. A piece of sagittal fascial wound from the linea alba was fixed in 10% formalin on ice for 6 h, dehydrated through graded sucrose washes for 24 h, and finally embedded in O.C.T. compound and snapped in liquid nitrogen. Serial cryostat sections were made for fluorescence microscopy to evaluate the distribution or localization of GFP-positive cells.

Statistics Statistical analysis was performed using GraphPad Prism version 4.0 for Windows. A t-test was used to compare the difference between the NS control group and AMP-treated groups. This software was also used to create the incidence curves of incisional hernia at POD 28 for fractional hernia of any particular hernia or wound defect size and to compare the curves between the NS-H control and AMP-H groups. The significance level was set at P<0.05.

Results Viability of AMP in Laparotomy Wounds and Hernias Successful transplantation requires clinical viability of the transplanted AMP. To test the survival of AMP cells in our models, 2.5×106 AMP-GFP cells were injected into the linea alba, and laparotomies were performed. Rats were killed on PODs 7, 14, and 28, and laparotomy tissue was collected. Frozen-tissue sections were prepared for fluorescence microscopy. AMP cells expressed GFP in laparotomy wound sections on PODs 7, 14, and 28, confirming AMP cell viability over this time course (⊡ Fig. 52.1).

AMP Cells Accelerate Laparotomy Healing Tensiometric measurements found significant differences in mechanical properties of the NS-S and AMP-S groups following laparotomy. All wounds were disrupted at the fascia–fascia interface of

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⊡ Fig. 52.1. Viability of humanamnion-derived multipotent progenitor cells labeled with green fluorescent protein (AMP-GFP) in laparotomy wounds. AMP-GFP were injected in the rat linea alba, and tissue was harvested at postoperative days (PODs) 7, 14, and 28. Frozen-tissue sections of abdominal wall collected at these three time points were examined under a fluorescent microscope. a POD 7. b POD 14. c POD 28. d Frozen skin tissue section adjacent to injection site collected on POD 7

a

b

c

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405 Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

the laparotomy wound. Wounds treated with 106 AMP cells developed increased breaking strength by POD 7 (⊡ Fig. 52.2). Laparotomy scar tissue sampled on POD 7 showed greater vascularization and fibrosis in the AMP-S group compared with the NS-S group (⊡ Fig. 52.2g, h). Wound strength properties continued to increase until POD 28. Differences in the recovery of wound-breaking properties were less on PODs 14 and 28, which is consistent with normal acute wound healing in the NS control group.

AMP Cells Reduce Laparotomy Dehiscence and Herniation To test whether accelerated laparotomy repair using AMP cells prevented hernia formation, AMP cells or NS was delivered to the linea alba in the hernia model. The hernia or wound defect size in the AMP-H group was significantly smaller than in the NS-H group (0.82±0.16 cm2 vs 2.72±0.56 cm2; ⊡ Fig. 52.3). Histology of the healing laparotomy (⊡ Fig. 52.3b) or hernia ring (⊡ Fig. 52.3c) showed again that there was more vascularization and fibrosis in the AMP-H rats, suggesting accelerated and improved laparotomy wound repair in the AMP-H group. In the best clinical study of predicting incisional hernias, it was found that a 12-mm gap in the laparotomy closure on POD 30 results in incisional hernia 94% of the time. Conversely, only 3% of defects less than 12 mm in size developed incisional hernias over 3 years [1]. Small laparotomy defects do not form incisional hernias, but bigger ones do. The majority of AMP-treated animals developed very small laparotomy defects, if at all. The largest and smallest hernia or defect sizes were 1.88 cm2 and 0 cm2, respectively, in the AMP-H group vs. 6.28 cm2 and 0.50 cm2, respectively, in the NS-H group. AMP treatment therefore reduces the incidence of laparotomy wound failure that progresses to incisional hernia.

Discussion The two fundamental mechanisms for laparotomy wound failure leading to incisional hernia may

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be summarized as follows: (1) A primary defect or delay in repair cell activation and provisional wound matrix crystallization during acute fascial repair causes herniation, or (2) mechanical failure and dehiscence cause a delay or deficiency in the acute wound-healing process [3]. The first is an inherited biological mechanism, and the second is an acquired biomechanical or biosurgical mechanism. It is possible that both mechanisms are active in a reinforcing cycle of surgical wound failure and herniation. Wound breaking strength is the mechanical property of a laparotomy that determines its ability to resist distractive forces. Burst abdomens, or acute fascial dehiscence with evisceration, are one important extreme of laparotomy failure. Studies report that amniotic cell therapy improves spinal injury and does not induce an immune rejection reaction [17, 21–23]. Human amniotic epithelial cells are not reported to express surface HLA-A, -B, -C, or -DR antigens or beta 2-microglobulin [21]. Human amnion epithelial cells are also reported to survive up to 7 weeks in vivo after allogeneic transplantation without inducing acute immune rejection. Other researchers found no residual amniotic epithelium in humans 2–3 months after human amniotic cell implantation [24]. These findings support its therapeutic safety. There are several potential mechanisms by which AMP cells improve healing of laparotomy incisions. AMP cells may differentiate into mesenchymal, fibroblast-like repair cells to replace or augment fibroblasts in the failing laparotomy wound. It is also possible that a repair or regeneration signal secreted by AMP cells directs accelerated and/or normal fascial fibroblast repair [25]. Our group has already reported the use of individual growth factors–TGF-B2, bFGF, and GMCSF–to accelerate laparotomy repair and prevent incisional hernia formation [5, 26, 27]. Tissue growth factors are an important class of tissue repair signaling peptides that are upregulated during the lag phase of acute wound healing [27]. However, 5–7 days are required before peak levels of fibroproliferative growth factors such as TGF-β are reached in acute wounds [28]. Acute wound therapy with proliferative growth factors is

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Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

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⊡ Fig. 52.2. Tensiometric measurements and histology exam on postoperative day (POD) 7. Fascial mechanical breaking characteristics were measured with an Instron tensiometer on POD 7 (a–f). Values are the mean ± SEM of six wound biopsies each from the normal saline (NS) control (NS-S) and the NS-washed human-amnion-derived multipotent progenitor cell (AMP-S) groups. A t-test was used to compare the difference between the two groups [single asterisk (*): p<0.05; double asterisk (**): p<0.01]. Morphology of fascial incisional wound at POD 7 from the NS-S (g) and AMP-S (h) groups. Hematoxylin and eosin staining was performed for histology

407 Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

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⊡ Fig. 52.3. Effect of human-amnion-derived multipotent progenitor (AMP) cells on hernia healing. Hernia or wound defect size was measured on postoperative day 28. Values are the mean ± SEM of 11 hernia biopsies each from the normal saline (NS) control (NS-H) and the AMP-hernia groups. [Double asterisk (**): compared with NS-H, p<0.01]. Morphology of hernia ring from the normal saline (NS) control (b) and NSwashed AMP (c) groups. Hematoxylin and eosin staining was performed on tissue sections

known to accelerate the appearance of fibroblasts and collagen into the wound, thereby shortening the natural lag phase for gain in injured tissue strength. The preponderance of clinical and preclinical evidence supports the concept that very early laparotomy wound failure is the mechanism of incisional hernia formation. Load-bearing laparotomy wounds fail at the weakest point on the acute wound-healing trajectory at the same time that surgical patients are recovering. Early wound failure results in incisional hernia formation 94% of the time [1, 2]. Well-performed, prospective series of incisional hernia repairs report early recurrences, most within 3 years of operation. It is therefore increasingly accepted that the majority

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of incisional hernias arise from occult fascial dehiscences, so a new emphasis is being placed on improved laparotomy closure and healing, through either biological manipulation or the use of prophylactic soft tissue prostheses. Preclinical work has confirmed that accelerated laparotomy repair through priming with tissue repair growth factors can significantly reduce the incisional hernia rate [4, 5]. The problems with single-peptide wound therapy remain drug delivery, dosing, and timing. Histological samples of AMP-treated wounds are consistent with accelerated repair compared with controls. There is more fibroplasia and angiogenesis, and it is also suggested that the intensity of the wound inflammatory response is modulated and less severe. Collagen fibrils appear to be more organized along natural lines of tension, and the peritoneal lining appears restored during AMP treatment. A comprehensive examination of remote organs and tissue found no migration or trafficking of AMP cells beyond the wound (data not shown). This supports the application of AMP cells in wound therapy. The immune privilege of amnion-derived cells permits their use as an allograft, and the containment of these cells to the wound suggests their safety.

References 1. Pollock AV, Evans M. Early prediction of late incisional hernias. Br J Surg 1989;76:953–4 2. Burger JW, Lange JF, Halm JA, Kleinrensink GJ, Jeekel H. Incisional hernia: early complication of abdominal surgery. World J Surg 2005;29(12):1608–13 3. Dubay DA, Franz MG. Acute wound healing: the biology of acute wound failure. Surg Clin North Am 2003;83(3):463–81 4. Dubay DA, Wang X, Kuhn MA, Robson MC, Franz MG. The prevention of incisional hernia formation using a delayed-release polymer of basic fibroblast growth factor. Ann Surg 2004;240(1):179–86 5. Franz MG, Kuhn MA, Nguyen K et al. Transforming growth factor β2 lowers the incidence of incisional hernias. J Surg Res 2001;97(2):109–16 6. Robson MC, Dubay DA, Wang X, Franz MG. Effect of cytokine growth factors on the prevention of acute wound failure. Wound Repair Regen 2004;12(1):38–43 7. Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF. Accelerated healing of incisional wounds in rats induced by transforming growth factor-α. Science 1987;237:1333–6

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Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

8. Yamaguchi Y, Kubo T, Murakami T et al. Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing. Br J Dermatol 2005;152(4):616–22 9. Han SK, Yoon TH, Lee DG, Lee MA, Kim WK. Potential of human bone marrow stromal cells to accelerate wound healing in vitro. Ann Plast Surg 2005;55(4):414–9 10. Chunmeng S, Tianmin C, Yongping S et al. Effects of dermal multipotent cell transplantation on skin wound healing. J Surg Res 2004;121(1):13–9 11. Robson MC. Cytokine manipulation of the wound. Clin Plast Surg 2003;30(1):57–65 12. Fliniaux I, Viallet JP, Dhouailly D, Jahoda CA. Transformation of amnion epithelium into skin and hair follicles. Differentiation 2004;72(9-10):558–65 13. Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells 2005;23(10):1549–59 14. Tahara M, Tasaka K, Masumoto N et al. Expression of messenger ribonucleic acid for epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor in human amnion cells: possible role of TGF alpha in prostaglandin E2 synthesis and cell proliferation. J Clin Endocrinol Metab 1995;80(1):138–46 15. Padowska E, Blach-Olszewska Z, Gejdel E. Constitutive and induced cytokine production by human placenta and amniotic membrane at term. Placenta 1997;18:441–6 16. Denison FC, Kelly RW, Calder AA, Riley SC. Cytokine secretion by human fetal membranes, decidua and placenta at term. Hum Reprod 1998;13(12):3560–5 17. Wu ZY, Hui GZ, Lu Y, Wu X, Guo LH. Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury. Chin Med J (Engl ) 2006;119(24):2101–7 18. Franz MG, Smith PD, Wachtel TL et al. Fascial incisions heal faster than skin: a new model of abdominal wall repair. Surgery 2001;129(2):203–8 19. Dubay DA, Wang X, Adamson BS, Kuzon Jr WM, Dennis RG, Franz MG. Progressive fascial wound failure impairs subsequent abdominal wall repairs: a new animal model of incisional hernia formation. Surgery 2005;137(4):463–71 20. Dubay DA, Choi W, Urbanchek MG, Kuzon WM, Franz MG. Incisional herniation induces decreased abdominal wall compliance via oblique muscle atrophy and fibrosis. Ann Surg 2007;245(1):140–6 21. Adinolfi M, Akle CA, McColl I et al. Expression of HLA antigens, beta 2-microglobulin and enzymes by human amniotic epithelial cells. Nature 1982 28;295(5847):325–7 22. Akle CA, Adinolfi M, Welsh KI, Leibowitz S, McColl I. Immunogenicity of human amniotic epithelial cells after transplantation into volunteers. Lancet 1981 7;2(8254): 1003–5 23. Sankar V, Muthusamy R. Role of human amniotic epithelial cell transplantation in spinal cord injury repair research. Neuroscience 2003;118(1):11–7

24. Yeager AM, Singer HS, Buck JR et al. A therapeutic trial of amniotic epithelial cell implantation in patients with lysosomal storage diseases. Am J Med Genet 1985; 22(2):347–55 25. Steed DL, Trumpower C, Duffy D et al. Amnion-derived cellular cytokine solution: a physiological combination of cytokines for wound healing. Eplasty 2008;8:e18 26. Dubay DA, Wang X, Kirk S, Adamson BS, Robson MC, Franz MG. Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts. Wound Repair Regen 2004;12(5):539–45 27. Robson MC, Mustoe TA, Hunt TK. The future of recombinant growth factors in wound healing. Am J Surg 1998;176(suppl 2A):80–2 28. Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, Norton JA. Transforming growth factor beta levels in rat wound chambers. J Surg Res 1987;42:622–8

Discussion Amid: Now we have more than 250 meshes, and

our challenge remains the same. So I think it’s time to [take the] focus from the mesh to the host. And that is what you are doing. Franz: Thank you. Klinge: I am not really convinced about the classification into big and small recurrences. I think if you create a wound within the abdominal wound, you always have an immigration of stem cells. Do you have any information that in patients with impaired wound healing it is this process of adult local stem cells that is impaired? And correspondingly, these patients would benefit from some additional stem cells? Franz: There is evidence in the literature that the amount of defect in the primary laparotomy will predict late incisional hernia—it was published in the British Journal of Surgery in 1989. The authors were able to predict the future incisional hernia based on the size of the hernia defect. Thus, it may matter. Miserez: Congratulations on this wonderful lecture. You used human stem cells in the rat model. Should we work on interspecies in the future, or should we stay in one species, with autologous material? Franz: It is possible. In practical surgery it is nice to have a product that is available. It may not matter what the species is.

409 Chapter 52 · The Role of Stem Cells in Abdominal Wall Repair

Schumpelick: Have you done experiments with

fibroblasts? Franz: No. There is a group from Israel that has done that on mesh.

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Conclusion of Session IV, by A. Montgomery The session included both experimental investigations and studies and discussions. First of all, we had a good overview of the pathophysiology of the peritoneum and adhesion formation. Then we had a discussion on meshes in general and on biological meshes. I would say that the knowledge of meshes today is a mess. We are talking about shrinkage and expansion of meshes. The biological meshes have brought something new; we now have 13 FDA-approved biological meshes. There are a lot of things to study. What is the body’s reaction to these meshes? When to use them? Or should we use them at all? There is a lot of work to be done. I would combine that with a congratulation to the last lecture on stem cell biology and the possible new thinking. It might be a combination for the biological meshes—to overbridge a distance of about 20 cm with stem cell formation. This might be a future for the biological meshes. We also should concentrate on the effect of pore size. I also think that the surface area was a very interesting key in the discussion of meshes. With regard to the clinical part and laparoscopy, we could conclude that there is a total lack of evidence for any mesh to be used and in what situations. Better hernia classifications and hernia registries would enable more precise research.

V

V

Risk for Migration and Erosion

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Safety and Durability of Prosthetic Repair of the Hiatal Hernia: Lessons Learned from a 15-Year Experience – 413

54

Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty – 421

55

Complications After Gastric Banding–Results in Germany – 429

56

Alloplastic Implants for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse – 439

57

Prophylactic IPOM Mesh To Prevent Parastomal Hernias – 445

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Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications – 451

59

Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration and Shrinkage – 457

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Safety and Durability of Prosthetic Repair of the Hiatal Hernia: Lessons Learned from a 15-Year Experience P. von Ryll Gryska

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Chapter 53 · Safety and Durability of Prosthetic Repair of the Hiatal Hernia: Lessons Learned from a 15-Year Experience

Introduction

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Laparoscopic fundoplication has emerged as the gold standard for treating refractory reflux disease and symptoms of gastric herniation. Surgical success rates as measured by patient satisfaction and symptom relief have been reported to be between 85% and 95% [1, 2]. However, as with any operation, we should continue to critically examine clinical failures in an effort to identify and correct potential sources of technical weaknesses. There are several important technical features of standard hiatal hernia repair/fundoplication, including hernia sac excision, mobilization of the esophagus, return of the stomach and distal esophagus to the intraabdominal position, and crural repair and wrap. Each has been recognized as an important feature of a successful clinical outcome [3]. Breakdown of the hiatal hernia repair has also been recognized as a common cause for clinical failure, often within the first 2 years, leading to wrap herniation and paraesophageal herniation and contributing to the slipped Nissen phenomenon [4–6]. During the last 15 years, we have focused on hiatal hernia repair as a source of technical failure. A prosthetic patch of the esophageal defect or reinforcement of the crural closure was used on all patients. With experience, the technique has evolved from a pure nontension patch of the hiatal defect to partial crural closure with sutures reinforced with an expanded polytetrafluoroethylene (ePTFE)/ PTFE prosthesis stapled and sutured into position to prevent motion, migration, or erosion. In short, the crural closure is treated as a hernia repair anywhere else on the abdominal wall. Presented here are the lessons learned about the fixation, durability, and safety of prosthetic mesh at the hiatus.

Materials and Methods Records of 217 patients undergoing laparoscopic Nissen fundoplication were examined. Each patient had a prosthetic closure of the hiatal hernia or reinforcement of the crural repair. The first 112 patients (group A) had a nontension patch using a PTFE mesh stapled into position with 3 cm of mesh overlapping beyond crural bundles onto the

a

b ⊡ Fig. 53.1. a Staples and suture to right crus after crural closure. b Staples and suture to left crus

diaphragm [7]. The next 105 patients (group B) underwent hiatal hernia repair using an ePTFE/ PTFE prosthesis (CruraSoft; Davol/Bard). Fixation of this prosthesis as part of the crural closure evolved quickly to partial crural closure with one to three sutures and fixation of the prosthesis with staples (EMS 20; Ethicon) and 2-0 silk sutures (⊡ Fig. 53.1). The prosthesis was positioned onto the crural closure so that none of the material was abutting the esophagus. This required thorough esophageal mobilization and complete dissection of the crural columns posteriorly. The focus of the record review was on shortterm and long-term safety as well as durability of the prosthetic crural repair. Postoperative dysphagia, stricture, integrity of the crural repair, reherniation, and development of long-term complications were examined. Continuing analysis and retrospective review then permitted evaluation of the crural repair and fixation techniques that led to the best clinical outcomes.

415 Chapter 53 · Safety and Durability of Prosthetic Repair of the Hiatal Hernia

Results Beginning in November 1993, 217 patients underwent laparoscopic Nissen fundoplication with a nontension prosthetic closure of the hiatal defect (group A =112 patients) or prosthetic reinforcement of the hiatal hernia repair (group B =105 patients). Patient demographics are listed in ⊡ Table 53.1. Of note is the large number of type II and type III hiatal hernias, with 75 patients having »large« hiatal defects >6 cm. Twenty-two patients (10%) underwent concomitant cholecystectomy, and 11 patients were referred for recurrent hiatal hernias (2–26 years postoperative).

Short-Term Safety There were no deaths, no transfusions, and no intraabdominal or mediastinal infections. There was no tearing or disruption of crural tissues. Placement of the prosthetic patch or reinforcement took 3–5 min when staples alone were used. Adding two sutures to the fixation process added roughly 8–10 min to the procedure. Although most operations were class I, totally clean procedures without violation of the gastrointestinal tract, 10% of the patients had a cholecystectomy at the same time. One gastrotomy occurred during a redo operation, which was closed immediately without contamination, and one Collis–Nissen esophageal lengthening was performed. These events officially made these cases class II, clean-contaminated operations. Three urinary tract infections, two cases of cellulitis at an intravenous line site, three pneumonias (in large paraesophageal hernias), a port site infection, and sinusitis were treated aggressively. Sixteen postoperative fevers were related to atelectasis. There were no complications related to PTFE mesh fixation with staples or sutures. Dysphagia to solid foods occurred routinely in the 1st month after surgery, and patients were kept on a liquid or very soft diet. Dysphagia requiring endoscopic dilation after 6 weeks occurred in 36 patients (12%). Nineteen of these 36 patients had had preoperative dilatation for stric-

53

⊡ Table 53.1. Patient demographics 217 patients, 120 female, ages 19–87 (mean 57.5 years) Mean operating time: 155 min Pure paraesophageal hernias: 22 (10%) Large hiatal defects ≥6 cm: 75 patients (34.5%) Mean age with large defects: 69.7 years Mean operating time (large defects): 205 min

ture disease. Five patients in group A required two to four dilations. One patient developed a fibrous stricture of the esophageal hiatus 4 years after initial surgery and required reoperation. This patient had no intraluminal pathology or erosion. Five of 17 primary postoperative dysphagia patients were from group B, each requiring only one dilation.

Long-Term Safety There were 165 patients for whom data since November 1993 were available. Data were available on all group B patients. The mean follow-up was 71 months (6–173 months). Barium studies on 90 patients done 1 day to 8 years postoperatively (mean 38 months) found no impingement of the prosthesis onto the esophagus or stomach, and 116 endoscopies on 86 patients (8 weeks to 8 years postoperatively; mean 42 months) found no erosion or impingement. In the years since their index surgery, six patients have undergone cholecystectomy, two for acute disease; two patients had appendicitis; and five patients have been treated for diverticulitis. Nine other patients have had intraabdominal surgery, and two have had thoracic surgery. One patient had an esophagectomy for progressing Barrett’s, during which the pure mesh prosthesis was found to be thoroughly ingrown to the crus and required excision with scissors to allow room for the gastric tube [7]. Two patients had full-term pregnancies, with one cesarean section. There have been no mesh infections and no mesh erosions.

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Durability

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Failure of the hiatal hernia repair as determined by symptoms and/or x-ray findings of wrap herniation occurred in three patients (1.4%). Two required reoperation. Hiatal hernia disruption occurred, respectively, at 5 days, 2 weeks, and 2 months after surgery. The earliest failure, at 5 days, was a totally nontension PTFE repair (group A) and occurred after heavy lifting. The other two were technical failures in which the preshaped PTFE/ePTFE mesh was merely stapled to the left and right crus without crural closure and without sutures. In all subsequent patients (101 patients), the crura were closed partially or tightly to a 58-Fr bougie, and the prosthesis was secured in position with staples and sutures. All 217 patients underwent laparoscopic Nissen fundoplication after crural repair with a prosthesis. In total, there have been three reoperations: one for stricture developing 4 years after the initial surgery and two for disruption of the crural repair with wrap migration. The one late-occurring stricture and one crural disruption occurred in group A, the totally nontension group. Two disruptions of the crural repair occurred in group B before we learned to close the crus as a backing for the prosthesis and to suture as well as staple the prosthesis in place. Since the development of crural closure and suture fixation along with staples, there have been no crural disruptions or reherniations in the last 101 patients (follow-up 6–55 months).

Discussion It is recognized that disruption of the crural closure leads to wrap herniation and clinical failure. It should not surprise us that a primary tension closure of the crural pillars can fail. The crural pillars are pure muscle: There is no substantial fascia, no tendinous tissue, and no ligamentous fibers, and nowhere else in surgery do we close muscle to muscle and expect it to hold under tension. The myriad of studies [8–11] that show improved integrity of crural repair after prosthetic reinforcement force us to examine the next step: how to do it safely. Granderath et al. define the ideal mesh

as »easy to handle at laparoscopy, able to adhere to the diaphragmatic surface on one side and be benign to visceral surface on the other« [12]. The next challenge is to position the prosthesis properly and then secure it properly. Several authors have shown that disruption of the crural closure occurs frequently in the early postoperative months to years [13–16]. Filipi has shown that various »stressors« or intraabdominal pressures can predispose to crural disruption [17]. Meshed prostheses do become ingrown into the crural muscle with time [7]. Our clinical failures even with a prosthesis occurred within the first 2 months after a nontension repair and therefore are considered failures of fixation. In subsequent patients, then, the crus was closed with one to three sutures, depending on the size of the defect, to provide backing to the mesh and to provide substrate for staples, and sutures were added to the fixation to provide extra strength and prevent prosthetic movement until tissue ingrowth could occur. The problem of erosion was not seen in this series over 15 years, and yet there are scattered published reports of such and anecdotal reports (unpublished) to this author. Erosion could result from improper placement of the prosthesis, i.e., placing the prosthesis too far anterior and abutting the esophagus, which may not be mobilized fully from its posterior position. Erosion could also result from migration and motion of a free-floating prosthesis (e.g., Angelchik). For these reasons, the prosthesis is now fixed to a closed crural defect with sutures and staples and is positioned so that the esophagus does not touch any part of the prosthesis. The posterior wrap then further pulls the esophagus anteriorly and away from the crural repair. Short-term safety and avoidance of infection related to the prosthesis at the hiatus are really a function of careful surgical technique and positioning of the prosthesis on well-vascularized crural muscle. In our review, no intraabdominal or mediastinal infections were encountered despite 24/217 clean-contaminated procedures and 10 peripheral postoperative infections. Dysphagia after 6 weeks occurred, not surprisingly, in 19 patients who had required dilation preoperatively. In 17/217 patients, primary

417 Chapter 53 · Safety and Durability of Prosthetic Repair of the Hiatal Hernia

postoperative dysphagia was treated with dilation and seemed more a consequence of the wrap and postoperative scar retraction or motility issues than narrowing of the esophageal hiatus. Among group B patients, only 5/105 had late postoperative dysphagia consistent with primary crural closure or mesh at the hiatus. Only one patient had clinically significant hiatal scarring, resulting in late dysphagia at 4 years. This rare phenomenon is known to occur historically with primary closure alone and is poorly understood. Long-term safety after 15 years is quite satisfactory. Despite intraabdominal infections from subsequent disease and other elective clean-contaminated operations, the prosthetic meshes placed at the hiatus are not susceptible to bacterial seeding. Just as prostheses on the anterior abdominal wall are covered with a protective peritoneal covering, so too is the prosthesis at the hiatus [18]. Proper positioning and proper fixation of the prosthesis have prevented migration, impingement, and erosion into the esophagus. The smooth ePTFE surface of the patch used on the most recent 105 patients prevents tissue ingrowth and thereby prevents fistulization to the stomach. In a primary crural closure, one would not expect to see the top of the closure or the suture impinging on the esophagus at barium study or endoscopy. Similarly, with a properly placed prosthetic patch reinforcing the crural closure, no impingement was seen on barium study (90 patients) or endoscopy (116 endoscopies in 86 patients). This, too, is a consequence of proper placement and proper fixation of the prosthesis as well as thorough mobilization of the posteriorly seated intrathoracic esophagus. This mobilization is necessary to return the distal 2–3 cm of the esophagus to the intraabdominal position, and it helps lift the esophagus anteriorly away from the crural closure and any prosthetic reinforcement. The bulky posterior wrap further holds the esophagus anteriorly away from the top of the closure. Most often, the prosthesis is placed below the top of the crural closure. The approximated hiatal closure provides a substrate behind the mesh for both near-term fixation with staples and long-term tissue ingrowth. The fixation with 15–20 staples (not tacks) and the addition of two sutures to fix the mesh to the

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crus in a full-thickness fashion further secure the prosthesis and prevent long-term migration and erosion (⊡ Fig. 53.1). Suturing of the stomach, the wrap, or the esophagus to the prosthesis is to be avoided. Durability of the hiatal hernia repair using a prosthesis has also been quite satisfactory in this experience. In three patients, breakdown occurred at 5 days, 2 weeks, and 2 months, respectively. Two patients underwent subsequent repair with prostheses. The very early failure was a consequence of extreme Valsalva at postoperative day 5 on a nontension repair. The next two breakdowns were a failure of proper fixation, in which the PTFE/ ePTFE prosthesis was merely stapled to the crural columns without closure (also nontension). It quickly became apparent that crural backing was necessary for secure fixation as well as for long-term tissue ingrowth. The technique evolved quickly and incorporated fixation sutures on either side of the prosthesis, incorporating the fullthickness crural column and the inner aspect of the prosthesis (⊡ Fig. 53.1). Now, after 15 years, 214 of 217 patients have had successful long-term treatment of their hiatal hernias. The hiatal hernia repairs remain intact after initial experience using a nontension prosthetic repair (111 patients) or subsequent experience with 101 patients in whom a primary crural repair was reinforced with a PTFE/ePTFE prosthesis. The PTFE/ePTFE prosthesis was thought to be safer with the ePTFE surface facing the viscera and thereby preventing tissue ingrowth and erosion. Seventy-five patients in this series had hiatal defects measuring 6 cm or greater. This large percentage of type II and type III hernias (34%) reflects an aging population (the mean age of this subset was 69 years), the increasing use of endoluminal therapies for small hiatal hernias, and a continuing reluctance of gastroenterologists to surrender pure reflux disease that can be medically managed. This 15-year experience hopes to show that hiatal hernia repair can be made durable with the use of prosthetic reinforcement and can be done safely using lessons learned from other prosthetic hernia repairs. The superiority of prosthetic repair has been demonstrated in numerous studies over the last

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Chapter 53 · Safety and Durability of Prosthetic Repair of the Hiatal Hernia: Lessons Learned from a 15-Year Experience

⊡ Table 53.2. Review articles of studies comparing primary crural closure vs. prosthetic hiatal hernia repair Authors

Year

Number of patients

Targarona et al. [19]

2004

480

Granderath et al. [12]

2006

766

Johnson et al. [20]

2006

639

7.

8.

9.

10.

decade and includes three review articles (⊡ Table 53.2) [12, 19, 20]. With thousands of patients in hundreds of studies, ethically the time has passed for randomization of primary repair versus prosthetic repair of hiatal hernia. Although there are surgeons who are capable of tailoring crural repair to the individual patient [21], it may be safer for the general surgeon at large if we as a community can further define the best practice. Prosthetic reinforcement of the crural repair should now be considered the standard of care. Remaining challenges include the ideal prosthesis, proper positioning, and proper fixation.

11.

12.

13.

14.

References

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1. Terry M, Smith DC, Branum GD, Galloway K, Waring JP, Hunter JG (2001) Outcomes of laparoscopic fundoplication for gastroesophageal reflux disease and paraesophageal hernia. Surg Endosc 15:691–699 2. Cowgill SM, Gillman R, Kraemer E, Al-Saadi S, Villadolid D, Rosemurgy A (2007) Ten-year follow up after laparoscopic Nissen fundoplication for gastroesophageal reflux disease. Am Surg 73(8):748–752 3. Cuschieri A, Shimi S, Nathanson LK (1992) Laparoscopic reduction, crural repair, and fundoplication of large hiatal hernia. Am J Surg 163:425 4. Basso N, De Leo A, Genco A, Rosato P, Rea S, Spaziani E, Primavera A (2000) 360 degrees laparoscopic fundoplication with tension-free hiatoplasty in the treatment of symptomatic gastroesophageal reflux disease. Surg Endosc 14(2):164–169 5. Kamolz T, Granderath FA, Bammer T, Pasiut M, Pointner R (2002) Dysphagia and quality of life after laparoscopic Nissen fundoplication in patients with and without prosthetic reinforcement of the hiatal crura. Surg Endosc 16:572–577 6. Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP (2002) A prospective, randomized trial of laparoscopic polytetrafluoroethylene (PTFE) patch repair vs simple

15.

16. 17.

18.

19. 20.

21.

cruroplasty for large hiatal hernia. Arch Surg 137(6):649– 652 Gryska PV, Vernon JK (2005) Tension-free repair of hiatal hernia during laparoscopic fundoplication: a ten-year experience. Hernia 9(2):150–155 Turkcapar A, Kepenekci I, Mahmoud H, Tuzuner A (2007) Laparoscopic fundoplication with prosthetic hiatal closure. World J Surg 31(11):2168 Müller-Stich BP, Holzinger F, Kapp T, Klaiber C (2006) Laparoscopic hiatal hernia repair: long-term outcome with the focus on the influence of mesh reinforcement. Surg Endosc 20(3):380–384 Lee YK, James E, Bochkarev V, Vitamvas M, Oleynikov D (2008) Long-term outcome of cruroplasty reinforcement with human acellular dermal matrix in large paraesophageal hiatal hernia. J Gastrointest Surg 12(5):811–815 Granderath FA, Schweiger UM, Kamolz T, Pasiut M, Haas F, Pointner R (2002) Laparoscopic antireflux surgery with routine mesh-hiatoplasty in the treatment of gastroesophageal reflux disease. J Gastrointest Surg 6(3):347– 353 Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, Frantzides CT (2006) Prosthetic closure of the esophageal hiatus in the large hiatal hernia repair and laparoscopic anti reflux surgery. Surg Endosc 20:367– 379 Endzinas Z, Jonciauskiene J, Mickevicius A, Kiudelis M (2007) Hiatal hernia recurrence after laparoscopic fundoplication. Medicina (Kaunas) 43(1):27–31 Hatch KF, Daily MF, Christensen BJ, Glasgow RE (2004) Failed fundoplications. Am J Surg 188(6):786–791 Hunter JG, Smith CD, Branum GD, Waring JP, Trus TL, Cornwell M, Galloway K (1999) Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision. Ann Surg 230(4)595–606 Filipi CJ (2000) Laparoscopic hiatal hernia repair: why they fail. Hernia 4:219–222 Kakarlapudi G, Awad Z, Haynatzki G, Sampson T, Stroup G, Filipi CJ (2002) The effect of diaphragmatic stressors on recurrent hiatal hernia. Hernia 6:163–166 Amid P, Shulman A, Lichtenstein I, Hakakha M (1994) Biomaterials for abdominal wall hernia surgery and principles of their applications. Langenbeck Arch Chir 379:168–171 Targarona EM, Bendaham G, Balague,C, Garriga J, Trias M (2004) Mesh at the hiatus. Arch Surg 139:1286–1296 Johnson JM, Carbonell AM, Carmody BJ, Jamal MK, Maher JW, Kellum JM, DeMaria EJ (2006) Laparoscopic mesh hiatoplasty for paraesophageal hernias and fundoplications: a critical analysis of the available literature. Surg Endosc 20:362–366 Granderath FA, Schweiger UM, Pointner R (2007) Laparoscopic antireflux surgery: tailoring the hiatal closure to the size of the hiatal surface area. Surg Endosc 21:1900

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Discussion Fitzgibbons: I did not hear your failure rate. You told us a lot of information,but what was your failure rate? Gryska: Within this study I put the data together, and we had a clinical success rate equivalent to standard reflux surgery. We have a 92–93% clinical success rate. Fitzgibbons: The only thing I want to say is that we recently presented 25 cases of erosion. Gryska: I was unaware of that. Fitzgibbons: We collected them from all around the country. Gryska: I found six in the literature and three anecdotal. Fitzgibbons: And we found all types of materials, including biologicals. Surgisis, GoreTex, anything you can imagine. Gryska: We should take this message and pay attention to hernia and keep the prosthetic away from the esophagus. Flament: I am glad that Dr. Fitzgibbons said this. Because in our department within the last 2 years we had two cases of prosthesis migrating, and I cannot imagine having 25% of the world cases. There are a lot of cases never reported, and that is probably the case for most of the complications in every field of surgery. Gryska: I believe you are right. We just see the tip of the iceberg and have not yet come across the perfect mesh, the perfect way of fixating the mesh. I think as hernia surgeons we have to think about a better way. Schumpelick: Thank you for the comments. The reason we put this topic on the agenda was because 2½ years ago we had the topic of incisional hernia here in Suvretta, and we had all the cracks of hiatal hernia here, but we did not get a real solution on how to handle it. Now we see good clinical results.

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Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty M. Jansen and J. Otto

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Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

Introduction Because of recurrence rates of up to 42% after Nissen fundoplication, the implantation of prosthetic material is recommended in cases of paraesophageal herniation [1, 2]. Clinical studies of patients with gastroesophageal reflux disease have shown that the recurrence of symptoms is mainly caused by intrathoracic herniation of the gastric wrap into the mediastinum [3–5]. Since the first description of hiatal mesh implantation by Kuster and Gilroy [6], many different techniques have been published [7]. Although large series of patients were treated, a good understanding of indications, mesh placement technique, mesh structure, and mesh material is still lacking. Most studies deal with the clinical outcome, such as dysphagia or recurrence rate. Only a few case reports give an account of mesh migration and perforation into the esophagus [8, 9]. One current article by Desai and colleagues deals with histological results 1 year after bioprosthetic repair of paraesophageal hernia with a new small intestinal submucosal (SIS) mesh. The authors found no evidence of erosion of SIS mesh into the esophagus [10]. To examine functional and histological changes in the distal esophagus after implantation of two different alloplastic mesh materials, we performed an animal study in rabbits.

a

b

⊡ Fig. 54.1. a Polypropylene–polyglecaprone 25 composite mesh fixed to the esophageal hiatus, intraoperative view. b Polypropylene mesh fixed to the esophageal hiatus, intraoperative view

Materials and Methods

54

Animals and Anesthesia A total of 20 female chinchilla rabbits (mean body weight 2.5±0.3 kg) were included in this study. The rabbits were randomly assigned to two different groups of equal numbers. The surgical procedure was performed under sterile conditions and general anesthesia by intravenous administration of ketamine 10% (Sanofi-Ceva, Dusseldorf, Germany) and xylazine (Rompun 2%; Bayer, Leverkusen, Germany) [11, 12]. The stomach and the distal esophagus were exposed. Two different meshes–polypropylene (PP; Prolene) and a polypropylene–polyglecaprone 25 composite (PP-PG; UltraPro)–were placed on the

hiatus as an anterior onlay patch overlapping the hiatal crura with a circular distance to the esophageal wall of 3 mm. The meshes had a diameter of 2 cm and were fixed to the diaphragm with four polypropylene (6-0) single stitches (⊡ Fig. 54.1). The abdominal cavity was closed with two running sutures of 3-0 polyglycolic acid.

Functional Analysis After 3 months the animals received general anesthesia again. A small gastric tube (6 Ch) was inserted into the proximal esophagus, and watersoluble iodine contrast medium was injected very carefully into the esophagus until deglutition was

423 Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

initiated. The swallow was documented by continuous radioscopy.

Macroscopic Analysis The animals were killed by a lethal dose of pentobarbital sodium (Narcoren; Rhone Merieux, Laupheim, Germany). The abdominal cavity was reopened via a U-shaped incision in the upper abdomen for complete exploration. Adhesions to the mesh were examined and photo-documented, and the severity was registered according to a scoring system [13, 14].

Histochemistry and Immunohistochemistry

54

Statistical Analysis All data are expressed as mean ± standard error of the mean (SEM). Wilcoxon’s two-sample test was used for statistical analysis. Differences were considered statistically significant when p<0.05.

Results The initial surgical procedure was uneventful in all animals. Sixteen rabbits survived the complete observation period of 3 months. Four animals (three with PP, one with PP-PG) died of pneumonia. We found no complications caused by the surgical procedure.

Contrast Medium Swallow The distal esophagus and the diaphragm including the implanted mesh were resected en bloc and fixed in formaldehyde solution, and 5-μm sagittal sections were then stained with hematoxylin and eosin (H&E). Light microscopy was used to evaluate the foreign body reaction, localization of the mesh as related to the esophageal wall, and extent of esophageal stenosis. The foreign body reaction was analyzed quantitatively by measuring the diameters of the foreign body granuloma surrounding the mesh filaments. In brief, the granulomas were subdivided into »inner ring« granuloma, representing the inflammatory infiltrate, and »outer ring« granuloma, resulting from the fibrotic tissue reaction. After five granulomas per sample were captured with a digital camera (×400, Olympus C-3030, Hamburg, Germany), separate measurements of four quadrants of the inner and outer granuloma ring were made with the help of digital imageanalyzing software (Image-Pro Plus; Media Cybernetics, Silver Spring, MD, USA) [15]. The migration of the mesh into the esophageal wall was characterized as follows: 0= no contact between mesh and esophagus; 1= mesh migration into the outer longitudinal muscle; 2= mesh migration into the inner circular muscle; 3= mesh migration into the submucosal layer; 4= mesh migration into the esophageal lumen.

After 3 months we found a prolonged passage of contrast medium into the stomach in all operated animals, which was associated with a prestenotic dilatation of the distal esophagus. However, fluid passage was possible in all cases. A complete stenosis was not observed. The dilatation averaged 1.2±0.5 cm in the PP group compared with 1.0±0.3 cm in the PP-PG group (p=0.37; ⊡ Fig. 54.2).

⊡ Fig. 54.2. Swallow of water-soluble iodine contrast medium with esophageal dilatation due to polypropylene mesh implantation

424

Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

Histology 80 70 60

Diameter [μm]

We measured the granuloma diameter at the graft– tissue interface close to the esophagus as well as close to the diaphragm in order to evaluate the extent of foreign body reaction. The diameter of the inner ring close to the esophagus, representing the inflammatory infiltrate, was similar in both groups. The mean diameter was 19.2±1.9 μm after implantation of PP-PG mesh compared with 18.3±2.4 μm for the PP mesh (p=0.4). In contrast, we observed a significant increase in the outer ring of granuloma in the PP group (76.5±8.0) compared with the PP-PG group (64±8.5, p=0.002; ⊡ Fig. 54.3a, b).

50 40 30 20 10

a

0 inner granuloma

Mesh Migration

54

Prolene

90 80 70

Diameter [μm]

After 3 months, distinctive mesh shrinkage was observed in all animals, and meshes lost up to 50% of their original size (⊡ Fig. 54.4a, b). Because the contiguity to the distal esophagus was of paramount interest, we focused on the mesh migration into the esophageal wall. Only one of the implanted PP meshes was located within distance of the esophageal wall. Three (43%) meshes moved into the outer longitudinal muscle layer. Two (29%) were detected in the inner circular muscle layer. One (14%) mesh had perforated the muscle layer and migrated into the submucosa. The results for the PP-PG meshes were significantly different: Four (44%) meshes were located outside the esophageal wall, while three (30%) were detected in the outer longitudinal muscle and two (22%) in the inner circular muscle layer. It must be pointed out that both types of mesh left their implantation bed and migrated into the esophageal wall (⊡ Fig. 54.5).

Ultrapro

outer granuloma

60 50 40 30 20 10

b

0 inner granuloma Ultrapro

outer granuloma Prolene

Discussion

⊡ Fig. 54.3. a Diameter of inner and outer granuloma at the diaphragm after implantation of polypropylene (Prolene) and polypropylene–polyglecaprone 25 composite (UltraPro) mesh. b Diameter of inner and outer granuloma at the esophagus after implantation of polypropylene (Prolene) and polypropylene–polyglecaprone 25 composite (UltraPro) mesh

Johnson et al. [7] reviewed the literature on laparoscopic mesh hiatoplasty and concluded that current data »tend to support the use of prosthetic materials for hiatal repair.« Nevertheless, different techniques (anterior–posterior, onlay interposition) and mesh materials (polypropylene [16–19],

polytetrafluoroethylene [20, 21], Surgisis [22], Alloderm) were used, and the current data focus only on the clinical outcomes. However, data concerning implantation of alloplastic material for repairing incisional hernias

425 Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

a

a

b

b

54

⊡ Fig. 54.4. a Polypropylene–polyglecaprone 25 composite mesh 3 months after implantation; adhesion to the liver and stomach was removed. b Polypropylene mesh 3 months after implantation; adhesion to the liver and stomach was removed

⊡ Fig. 54.5. a Hematoxylin and eosin (H&E) staining of the distal esophagus (magnification ×40) with submucosal detection of mesh fibers (polypropylene). b H&E staining of the distal esophagus (magnification ×40) with detection of mesh fibers (polypropylene–polyglecaprone 25 composite) within the longitudinal esophageal muscle layer

show the superiority of reduced-material meshes with large pores to minimize the inflammatory response and scar formation [23–26]. Extensive work has led to several mesh modifications to adapt to physiological requirements and improve biocompatibility [15, 27, 28]. In particular, the drawbacks of PP mesh implantation have been elucidated and have led to mesh modifications such as combined mesh materials [28–30]. A new composite mesh consisting of a reduced amount of polypropylene supplemented with polyglecaprone 25 minimizes the development of granulomatous chronic foreign body reaction. Polyglecaprone 25 filaments were essentially degraded 84 days after implantation [31]. Requirements for

mesh materials used for the repair of hiatal hernias have not yet been shaped. Case reports indicate the problem of mesh migration into the esophagus, and, to the author’s knowledge, several oral reports on this topic were presented at different meetings in recent years. These reports may underscore the necessity to analyze the biological and functional outcomes of meshes used for hiatoplasty [9, 32]. A first attempt at mesh modification was done by Desai et al. [10]. The researchers found that implanting a small intestinal submucosal mesh led to good reinforcement of the hiatus with marginal foreign body reaction and native ingrowth of connective tissue and skeletal muscle. However, this type of mesh is not used widely in clinics.

426

Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

The results of our experiments clearly indicate that circular implantation of meshes around the esophagus leads to a high rate of mesh migration. Furthermore, heavyweight polypropylene meshes are less compatible compared with lightweight composite mesh (PP-PG). We found a higher rate of migration into the esophageal wall and an increased extent of foreign body reaction with PP mesh compared with the PP-PG mesh. These results are consistent with the biology of meshes used in the treatment of incisional hernias [33–35]. Although the data were generated in rabbits and have limited impact on humans, our presented animal model can be used to develop the necessary requirements for mesh hiatoplasty. More experimental data are necessary to assess the optimal size, structure, and positioning of prosthetic materials for mesh hiatoplasty [36, 37].

9.

10.

11.

12.

13.

14.

References 15.

54

1. Hashemi M, Peters JH, DeMeester TR, Huprich JE, Quek M, Hagen JA, Crookes PF, Theisen J, DeMeester SR, Sillin LF, et al. Laparoscopic repair of large type III hiatal hernia: objective followup reveals high recurrence rate. J Am Coll Surg 2000 May; 190(5):553–60 2. Granderath FA, Schweiger UM, Kamolz T, Pasiut M, Haas CF, Pointner R. Laparoscopic antireflux surgery with routine mesh-hiatoplasty in the treatment of gastroesophageal reflux disease. J Gastrointest Surg 2002 May; 6(3):347–53 3. Soper NJ, Dunnegan D. Anatomic fundoplication failure after laparoscopic antireflux surgery. Ann Surg 1999 May; 229(5):669–76 4. Hunter JG, Smith CD, Branum GD, Waring JP, Trus TL, Cornwell M, Galloway K. Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision. Ann Surg 1999 Oct; 230(4):595–604 5. Carlson MA, Frantzides CT. Complications and results of primary minimally invasive antireflux procedures: a review of 10,735 reported cases. J Am Coll Surg 2001 Oct; 193(4):428–39 6. Kuster GG, Gilroy S. Laparoscopic technique for repair of paraesophageal hiatal hernias. J Laparoendosc Surg 1993 Aug; 3(4):331–8 7. Johnson JM, Carbonell AM, Carmody BJ, Jamal MK, Maher JW, Kellum JM, DeMaria EJ. Laparoscopic mesh hiatoplasty for paraesophageal hernias and fundoplications: a critical analysis of the available literature. Surg Endosc 2006 Mar; 20(3):362–6 8. Arendt T, Stuber E, Monig H, Folsch UR, Katsoulis S. Dysphagia due to transmural migration of surgical material

16.

17.

18.

19.

20.

21.

22.

23.

into the esophagus nine years after Nissen fundoplication. Gastrointest Endosc 2000 May; 51(5):607–10 Gajbhiye R, Quraishi AH, Mahajan P, Warhadpande M. Dysphagia due to transmural migration of polypropylene mesh into esophagus. Indian J Gastroenterol 2005 Sep; 24(5):226–7 Desai KM, Diaz S, Dorward IG, Winslow ER, La Regina MC, Halpin V, Soper NJ. Histologic results 1 year after bioprosthetic repair of paraesophageal hernia in a canine model. Surg Endosc 2006 Nov; 20(11):1693–7 Treutner KH, Bertram P, Lerch MM, Klimaszewski M, Petrovic-Kallholm S, Sobesky J, Winkeltau G, Schumpelick V. Prevention of postoperative adhesions by single intraperitoneal medication. J Surg Res 1995 Dec; 59(6):764–71 Muller SA, Treutner KH, Jorn H, Anurov M, Oettinger AP, Schumpelick V. Phospholipids reduce adhesion formation in the rabbit uterine horn model. Fertil Steril 2002 Jun; 77(6):1269–73 Zuhlke HV, Lorenz EM, Straub EM, Savvas V. [Pathophysiology and classification of adhesions]. Langenbecks Arch Chir Suppl II Verh Dtsch Ges Chir 1990; 1009–16 Leach RE, Burns JW, Dawe EJ, SmithBarbour MD, Diamond MP. Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel. Fertil Steril 1998 Mar; 69(3):415–8 Rosch R, Junge K, Quester R, Klinge U, Klosterhalfen B, Schumpelick V. Vypro II mesh in hernia repair: impact of polyglactin on long-term incorporation in rats. Eur Surg Res 2003 Sep; 35(5):445–50 Granderath FA, Kamolz T, Schweiger UM, Pointner R. Impact of laparoscopic Nissen fundoplication with prosthetic hiatal closure on esophageal body motility: Results of a prospective randomized trial. Arch Surg 2006 Jul; 141(7):625–32 Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, Frantzides CT. Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery. Surg Endosc 2006 Mar; 20(3):367–79 Granderath FA, Kamolz T, Schweiger UM, Pointner R. Prosthetic material for crural closure in laparoscopic antireflux surgery. Surg Endosc 2004 Jan; 18(1):171–2 Keidar A, Szold A. Laparoscopic repair of paraesophageal hernia with selective use of mesh. Surg Laparosc Endosc Percutan Tech 2003 Jun; 13(3):149–54 Frantzides CT, Madan AK, Carlson MA, Stavropoulos GP. A prospective, randomized trial of laparoscopic polytetrafluoroethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg 2002 Jun; 137(6):649–52 Hui TT, Thoman DS, Spyrou M, Phillips EH. Mesh crural repair of large paraesophageal hiatal hernias. Am Surg 2001 Dec; 67(12):1170–4 Oelschlager BK, Barreca M, Chang L, Pellegrini CA. The use of small intestine submucosa in the repair of paraesophageal hernias: initial observations of a new technique. Am J Surg 2003 Jul; 186(1):4–8 Klosterhalfen B, Klinge U, Hermanns B, Schumpelick V. [Pathology of traditional surgical nets for hernia repair

427 Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

24.

25. 26.

27.

28.

29.

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31.

32.

33.

34.

35.

36.

37.

after long-term implantation in humans]. Chirurg 2000 Jan; 71(1):43–51 Schumpelick V, Klinge U, Welty G, Klosterhalfen B. [Meshes within the abdominal wall]. Chirurg 1999 Aug; 70(8):876–87 Conze J, Klinge U, Schumpelick V. [Incisional hernia]. Chirurg 2005 Sep; 76(9):897–909 Conze J, Kingsnorth AN, Flament JB, Simmermacher R, Arlt G, Langer C, Schippers E, Hartley M, Schumpelick V. Randomized clinical trial comparing lightweight composite mesh with polyester or polypropylene mesh for incisional hernia repair. Br J Surg 2005 Dec; 92(12):1488–93 Klinge U, Junge K, Spellerberg B, Piroth C, Klosterhalfen B, Schumpelick V. Do multifilament alloplastic meshes increase the infection rate? Analysis of the polymeric surface, the bacteria adherence, and the in vivo consequences in a rat model. J Biomed Mater Res 2002; 63(6):765–71 Klinge U, Klosterhalfen B, Ottinger AP, Junge K, Schumpelick V. PVDF as a new polymer for the construction of surgical meshes. Biomaterials 2002 Aug; 23(16):3487–93 Conze J, Junge K, Klinge U, Weiss C, Polivoda M, Oettinger AP, Schumpelick V. Intraabdominal adhesion formation of polypropylene mesh. Influence of coverage of omentum and polyglactin. Surg Endosc 2005 Jun; 19(6):798–803 Conze J, Rosch R, Klinge U, Weiss C, Anurov M, Titkowa S, Oettinger A, Schumpelick V. Polypropylene in the intraabdominal position: influence of pore size and surface area. Hernia 2004 Dec; 8(4):365–72 Junge K, Rosch R, Krones CJ, Klinge U, Mertens PR, Lynen P, Schumpelick V, Klosterhalfen B. Influence of polyglecaprone 25 (Monocryl) supplementation on the biocompatibility of a polypropylene mesh for hernia repair. Hernia 2005 Oct; 9(3):212–7 Hergueta-Delgado P, Marin-Moreno M, Morales-Conde S, Reina-Serrano S, Jurado-Castillo C, Pellicer-Bautista F, Herrerias-Gutierrez JM. Transmural migration of a prosthetic mesh after surgery of a paraesophageal hiatal hernia. Gastrointest Endosc 2006 Jul; 64(1):120 Klinge U, Klosterhalfen B, Muller M, Schumpelick V. Foreign body reaction to meshes used for the repair of abdominal wall hernias. Eur J Surg 1999 Jul; 165(7):665–73 Klinge U, Klosterhalfen B, Muller M, Ottinger AP, Schumpelick V. Shrinking of polypropylene mesh in vivo: an experimental study in dogs. Eur J Surg 1998 Dec; 164(12):965–9 Klinge U, Klosterhalfen B, Conze J, Limberg W, Obolenski B, Ottinger AP, Schumpelick V. Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. Eur J Surg 1998 Dec; 164(12):951–60 Aly A, Munt J, Jamieson GG, Ludemann R, Devitt PG, Watson DI. Laparoscopic repair of large hiatal hernias. Br J Surg 2005 May; 92(5):648–53 Andujar JJ, Papasavas PK, Birdas T, Robke J, Raftopoulos Y, Gagne DJ, Caushaj PF, Landreneau RJ, Keenan RJ. Laparoscopic repair of large paraesophageal hernia is associated with a low incidence of recurrence and reoperation. Surg Endosc 2004 Mar; 18(3):444–7

54

Discussion Kukleta: I would like to make a comment on the strategy of the team of Pointner and Granderath. It is a pity that they are not here, because they represent a very big experience in this field. It is obvious that they achieved good results with these very small one to three hernias and a mesh placed posteriorly, and they improved their recurrence rate immensely. And the number three and four are obvious too, because for the very large paraesophageal hernia, this was not enough. So the condition of the crura was responsible for the two branches. If the crura are fine, they rely on the crural suture repair, and then they packed it posteriorly. The other ones are the desperate cases which you nearly cannot suture, and nobody believes that that region can be tension-free covered for such a long time, but there are several papers from Italy where they placed a mesh circularly. Especially in the anterior part, the mesh gets very, very close to the esophagus. In the posterior part you can get the 1-cm distance, so you actually do not have any contact from the mesh to the esophagus. And if you do a fundoplication, it will cover the mesh. Jansen: I totally agree, and I think the idea of Granderath is not that bad. What I would like to avoid is that the indication for mesh implantation comes nowadays to the situation that you implant a mesh in every case. I do not think that is necessary. I totally agree that we have problems in dealing with these huge hiatal hernias, and for this indication a mesh is probably necessary. Matthews: We actually have a clinical trial going on right now with patients with type 1 hernias and type 3 hernias and in which we performed a biopsy of endoabdominal fascia. What we found was that these patients have tissue abnormalities that are different even between the type 1 and type 3 hernias, and so we are trying to understand more about the basics. Probably in the future we will be able to selectively use a mesh, as in inguinal hernia. Jansen: When I look at the literature, it is very interesting that people dealing with hiatal hernia have never read the huge [amount of] literature based on pathophysiological aspects of incisional hernia. There are so many questions not answered

428

54

Chapter 54 · Mesh Migration into the Esophageal Wall After Mesh Hiatoplasty

in this area concerning everything we discussed. Everyone tries a new shape of mesh or places meshes which were intended for incisional hernia for a long time. We have to think about the basics. What is the anatomy, the physiology? We need good experimental results before placing a mesh in every hiatal hernia. Schippers: On Wednesday we had a lot of discussion concerning animal models, looking for the influence of meshes on the cord. And at that time we were wondering whether the rat model is the appropriate animal. Maybe you would have had fewer reactions to the mesh if you would have had bigger animals? Jansen: Yes, probably. Klinge: In this area, can it be a good indication to use biologicals? Jansen: Perhaps. Klinge: Is there any information from the literature? Jansen: I do not know any. Probably there is some clinical work on it. What you cannot find is any experimental work on biologics at the hiatus. Most of the studies are clinical and not basic scientific work. Chowbey: Repairing hiatal hernia, there is one point we are not considering seriously: The food bolus is coming from the esophagus, and it needs its space to go down to the stomach. Also, we have to keep in mind that there will be a certain amount of stasis in the lower part of the esophagus. If we keep these two points in mind, probably our repair will be better. Schumpelick: I would like to hear from the audience. Who is using a mesh in second-size hiatal hernias? ... Just three. And who never uses a mesh? … It is the majority. Chowbey: We have to look at the literature. As we moved on from suture to prosthetic repair in incisional hernia, there is the same trend in hiatal hernia. Gryska: The question I ask you is about the tailored approach. I fear that the average surgeon doing hiatal hernia surgery does not think as much as we do. Do you believe the tailored approach can be translated to general surgeons? Jansen: The question is, what is the definition of the tailored approach? I think in most cases,

probably 80–90% of normal hiatal hernias can be treated without a mesh with a primary suture. And there are 5–10%, large or paraesophageal hernias, which need a mesh. If you take this figure as the tailored approach, yes, probably we have to propagate it. But we probably do not need three to five different meshes for three to five different indications. Schüssler: I am the gynecologist in this room, and I am the least to give answers, but what I’d like to ask you is, we have these small babies with large diaphragmatic hernias being easily repaired by the pediatric surgeons without mesh materials. Is there anything to learn from them? Just an ignorant question. Maybe they can help a little bit. Jansen: I think it is a different situation. Diaphragmatic hernia cannot be compared to hiatal hernias. Kukleta: Just one more question. Do you think large paraesophageal hernias, type 3, are for every general surgeon? Jansen: No.

55

Complications After Gastric Banding–Results in Germany C. Stroh and T. Manger

430

Chapter 55 · Complications After Gastric Banding–Results in Germany

Introduction Worldwide, approximately 1.7 billion people are overweight or obese [16, 23, 63]. Morbid obesity is associated with numerous comorbidities such as diabetes, hypertension, cardiac diseases, sleep apnoea syndrome, and degenerative skeletal diseases. Every year, about 2.5 million obese people die from their comorbidities [62]. The costs of these comorbidities are estimated to exceed $117 billion per year in the United States [9]. In the international comparison, the Federal Republic of Germany is one of the countries with a very high prevalence of obesity. For this condition, gastric banding is the most frequently performed bariatric operation in Europe [3, 4, 30]. Complications such as slippage, pouch dilatation, and band disconnection can be treated by repositioning the band or by performing a bypass in the case of its failure, but band erosion always requires band removal. Neither the impact of the selected surgical procedure on perioperative morbidity, weight loss, and degree of decrease in comorbidities nor the profile of long-term complications have yet been investigated in prospective studies. Therefore, experiences with postoperative complications are presented with an emphasis on the necessity of quality assurance in the surgical treatment of morbid obesity in Germany.

Discussion

55

After Roux-en-Y gastric bypass, gastric banding is the most frequently performed bariatric operation worldwide. According to data compiled from meta-analysis, it is carried out in 95% of countries performing bariatric surgery (⊡ Table 55.1) [8]. Meta-analysis reports the amelioration of comorbidities such as diabetes, hypertension, hyperlipidaemia, and sleep apnoea without any recommendations regarding long-term complications. In the literature, only a few prospective randomised studies have been reported. These studies compare gastric banding with other bariatric procedures, especially with Roux-en-Y gastric bypass and sleeve gastrectomy. Otherwise, randomised trials

⊡ Table 55.1. Incidence of gastric banding worldwide [8] Patients

Countries

Roux-en-Y gastric bypass

65.11%

88%

Gastric banding

24.41%

95%

Vertical banded gastroplasty

5.43%

79%

Biliopancreatic diversion or duodenal switch

4.85%

67%

have compared low-pressure and high-pressure bands. Reports in the literature on complication rates come only from single centres. The patient’s outcome after gastric banding is influenced by the long-term complications: slippage, pouch dilatation, band migration, and port-site complications.

Slippage and Pouch Dilatation The incidence of slippage has decreased since the introduction of the »pars flaccida« technique (⊡ Figs. 55.1 and 55.2) [58]. Pouch dilatation is a long-term complication after gastric banding. Its incidence is influenced by the surgical approach (open vs. laparoscopic) and the technique (perigastric vs. pars flaccida). Opening the lesser sac during open band placement leads to a higher incidence of pouch dilatation than the laparoscopic approach does, with the creation of a small retrogastric channel. Data in the literature on the incidence of pouch dilatation are very heterogeneous because most studies include different approaches and techniques. Many reports have a follow-up of less than 5 years (⊡ Table 55.2).

Band Migration Intragastric band migration is characterised by a »silent« migration of the band into the stomach (⊡ Figs. 55.3 and 55.4) [57, 60]. Peritonitis symptoms are usually absent. Only very limited retrospective data obtained from long-term studies are available [8, 10, 34, 53, 64]. The incidence of band migration ranges from 0.6% to 11% according to

431 Chapter 55 · Complications After Gastric Banding–Results in Germany

55

⊡ Fig. 55.2. Slippage

⊡ Fig. 55.1. Slippage

⊡ Table 55.2. Literature review on pouch dilatation (BMI body mass index; PG perigastric; PF pars flaccida) First author

Year

Technique

n

BMI (kg/m²)

Pouch dilatation rate (%)

Maximum followup (months)

Forsell [19]

1999

PG

326

Unknown

0.6

78

Doldi [17]

2000

PG

172

46.3

5.8

Szould [53]

2002

PF

715

43.1

7.40

30

Steffen [43]

2003

PF

824

42.2

2.70

60

Celen [13]

2003

PG

625

40

5.6

Zinzindohoue [65]

2003

PG/PF

500

44.3

8.00

Weiner [59]

2003

PF

984

46.8

>3.7

99

Angrisani [4]

2004

PF

3,562

43.3

4.1

60 (16.1%)

Chevallier [11]

2004

PF

1,000

44.3

10.4

72

Martikainen [27]

2004

PG/PF

123

49

21.0

108

Ren [37]

2004

PF

445

49.6

3.1

18

Silecchia [41]

2004

PF

313

46.1

3.2

Unknown

Zehetner [64]

2004

PF

190

Unknown

2.60

72

Spivak [42]

2005

PF

500

45.2

9.6

Stroh [46]

2005

PG/PF

3,973

Unknown

7.3

120

Stroh [45]

2005

PG/PF

168

49.6

10.70

120

Michelotto [29]

2006

PG/PF

684

42.2

6.1

60

Schouten [39]

2006

PG/PF

177

44.6

10.7

94

Suter [52]

2006

PG/PF

317

43.5

6.3

96

Balsiger [6]

2007

PF

196

44

12.2

108

Faretti [18]

2007

PG/PF

1,791

46.2

3.9

147

432

Chapter 55 · Complications After Gastric Banding–Results in Germany

the literature [11, 28, 33, 40] (⊡ Table 55.3). In a few studies, band migration has been considered a complication of the first 2 postoperative years, caused by intraoperative gastric perforation [12, 13, 18, 24, 29, 55].

⊡ Fig. 55.3. Band migration

55

⊡ Fig. 55.4. Band migration

The data show an erosion rate of 60% in cases of intraoperative gastric perforation versus 3%. In our data, patients with a noncritical intake of nonsteroidal antirheumatic agents, bronchospasmolytic drugs, and anticoagulant substances showed a higher incidence of band migration. In 53.3% of cases with intragastric band migration, the patients had been treated with nonsteroidal antirheumatic substances (26.6%), anticoagulant substances (20.0%), or bronchospasmolytic agents (0.6%). That is why, in our opinion, these medications should be considered a further cause of band migration. Simultaneous cholecystectomy did not significantly increase the erosion risk in our study. Chronic inflammation at the tissue area covered by the band could be a further reason for the development of erosion [1]. For example, in our experience band migration occurs by 30–86 months postoperatively. Interestingly, the erosion rate increased with long-term follow-up [44, 46, 48–50, 52]. Band erosion can lead to a life-threatening condition in cases of upper gastrointestinal bleeding and bowel obstruction [15, 54]. Therefore, correct diagnosis is essential. In our study we did not seen any port infection in the first 3 months after operation and after band filling. In the literature, port infection has been reported to be the first symptom of erosion [25, 44]. However, our own data reveal varying intervals between the onset of port infection and the occurrence of erosion. The treatment depends on symptomatology (⊡ Fig. 55.5) [41]. We favour band removal in cases of complete erosion, using gastroscopy and the AMI Band Cutter (CJ Medical, Buckinghamshire, UK) [57]. Gastroscopy is recommended at several time points to recognise complete erosion; we prefer intervals of 8 weeks. In the literature, 4-month intervals have been reported [41]; such intervals require patient reporting of information on possible complications as well as an acceptable distance between the patient’s residence and the hospital. Laparoscopy with intraoperative gastroscopy using the AMI Band Cutter is a safe method of band removal. A lesion of the gastric wall can be sutured, and a drain can be placed. In patients with bleeding of the upper gastrointestinal tract or abscess, the band has to be removed via lapa-

55

433 Chapter 55 · Complications After Gastric Banding–Results in Germany

⊡ Table 55.3. Literature review on incidence of band migration (BMI body mass index; OP operation; PG perigastric; O open; L laparoscopic; SAGB Swedish Adjustable Gastric Bands; PF pars flaccida; HG Heliogast band) First author

Year

n

BMI

Forsell [19]

1999

326

4.6

Meir [28]

1999

122

Miller [30]

1999

158

43

Rate (%)

OP

OP

Type

Follow-up rate (%)

Maximum follow-up (months)

1.6

O/L

PG

SAGB

97

78

PG

Lap-Band

88

60

0.6

L

PG

SAGB

98

46

DeJonge [15]

2000

91

44.7

3.3

L

PG

Lap-Band

100

24

Doldi [17]

2000

172

46.3

0.6

O/L

PG

Lap-Band

99.4

72

Weiss [57]

2000

211

1.9

L

PG

Lap-Band

Baldinger [5]

2001

714

1.0

L

PG

SAGB

Holeczy [22]

2001

36

45.6

0

L

PG

Lap-Band

Silecchia [40]

2001

148

44.2

7.5

L

PG

Lap-Band

831

54

Niville [34]

2001

301

42.5

1.66

L

PG

Lap-Band

984

73

Belachew [7]

2002

763

42

0.9

L

PG

Lap-Band

90

66

O

PG

SAGB

Gustavsson [21]

2002

90

43

14.4

Szold [53]

2002

715

43.1

0.5

Wolff [61]

2002

256

47

0.8

33

24

30 PG/PF PF

Unknown SAGB

97

48

Steffen [43]

2003

824

42.2

1.6

L

Coskun [14]

2003

70

45.2

2.8

O/L

Vertuyen [56]

2003

727

45

1.4

PG

Lap-Band

Unknown

Weiner [59]

2003

984

46.8

0.3

L

PG/PF

Lap, HG, SAGB

972

99

Angrissani [4]

2004

3,562

43.4

2.1

L

PG/PF

161

60

Chapman [10]

2004

8,504

Chevallier [11]

2004

1,000

44.3

0.30

Martikainen [27]

2004

123

49.0

9.00

Mittermair [31]

2004

682

0.8

L

PF

SAGB

48

Silecchia [41]

2004

313

46.1

5.1

L

PG/PF

Lap-Band

90

Ren [37]

2004

445

49.6

0.2

L

PF

Lap-Band

18

Zehetner [64]

2004

190

Unknown

2.1

Abu-Abeid [2]

2005

754

L

PF

Lap-Band

Nocca [35]

2005

4,236

Stroh [46]

2005

3,973

Stroh [45]

2005

168

Michelotto [19]

2006

Suter [52]

2006

Lattuada [26]

Lap-Band

0.6

2.1 43.2

60 39

Unknown L

Lap-Band

72 108

72 40

1.6

L

PG/PF

All

1.0

O/L

PF/PG

All

120

49.6

4.2

O/L

PG/PF

Lap-Band

120

684

42.2

1.1

O/L

PG/PF

Unknown

317

43.5

9.5

L

PG/PF

Lap/SAGB

2007

571

42.9

0.52

L

PG/PF

Lap, HG, SAGB

100

Balsiger [6]

2007

196

44

1.5

L

PF

SAGB

108

Favretti [18]

2007

1791

46.2

0.9

L

PG/PF

Lap-Band

145

60 81.5

96

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Chapter 55 · Complications After Gastric Banding–Results in Germany

Symptoms

Nonspecific symptoms Vomiting

Port infection

Bleeding Bowel obstruction

Contrast swallow Gastroscopy Abdominal ultrasound to exclude intraabdominal

Intraabdominal abscesses

Abdominal ultrasound Computed tomography

Removal of the port system

Band removal via gastroscopy using AMI Band Cutter (CJ Medical, Buckinghamshire, UK) after complete band migration

Laparoscopic band removal and intraoperative gastroscopy using AMI Band Cutter

Open band removal

⊡ Fig. 55.5. Differentiated treatment of gastric band migration [44]

55

rotomy if laparoscopy fails. Tangential resection of the gastric wall can become necessary in cases of massive bleeding. In the literature, a correlation of the erosion rate to the band type (high-pressure vs. low-pressure band) has not been described [20, 21, 54]. The data presented here show that the erosion rate of the LAP-Band (Inamed Health, Santa Barbara, CA, USA) is higher than that of the Gastrobelt (MEDING, Germany) or Swedish Adjustable Gastric Bands (SAGB; Obtech, Ethicon Endo-Surgery), but SAGB have been used only for the last 2 years. At the end of the 1990s, repositioning of the band in cases of slippage and pouch dilatation was widely performed, but the data from our study– with a higher incidence of gastric band migration–as well as the data in the literature show disappointing results [44, 45, 48]. That is why, in accordance with the literature [52], we see no indication for rebanding in cases of slippage or pouch dilatation. Band removal and rebanding

performed in one surgical intervention have been described in the literature [2]. Because of the different causes of band erosion and the significantly higher migration rate following intraoperative gastric perforation, and based on the currently available data, band removal in cases of erosion with simultaneous rebanding should not be performed since there is a potential risk of infection of the new band. In addition, because of the high failure rate after band revision, a conversion to Rouxen-Y gastric bypass or biliopancreatic diversion needs to be considered [31]. Since January 1, 2005, data collected in the German multicentre observational study for quality assurance in obesity surgery for all bariatric interventions and revisions have been available online for assessing the surgical treatment of morbid obesity [47]. Although patients are selected according to the guidelines of the International Federation for the Surgery of Obesity, the European Association for Endoscopic Surgery, and

435 Chapter 55 · Complications After Gastric Banding–Results in Germany

the German Society for Surgery of Obesity [38], substantial differences are encountered when comparing centres of bariatric surgery because of the regionally varying incidences of morbid obesity and the house policies of the different surgical departments. For instance, age and body mass index (BMI) of the surgically treated patients are significantly higher in Germany compared with data obtained in the meta-analysis on bariatric surgery [8]. In addition, significantly more patients suffer from type II diabetes mellitus and arterial hypertension. The possible consequence of a higher comorbidity rate is severe metabolic syndrome. The impact of a high(er) preoperative BMI on weight reduction needs to be investigated through a longterm study. Data obtained in the German multicentre observational study for quality assurance in obesity surgery also confirm the worldwide tendency towards combined and malabsorptive interventions to reduce both body weight and the frequency of comorbidities. This effect is underscored by the very high BMI of German patients. According to the literature, the reintervention rate per year of follow-up after a stomach volume operation is between 3% and 4% [6, 52]. Prospective long-term trials are necessary to detect short-term and long-term complications after different bariatric procedures. The amelioration of comorbidities should not be a single point of the studies because the complication rate after bariatric surgery seems to be higher than that reported in the literature. Predictive factors for patients’ election for different procedures should be evaluated to reduce the complication and reoperation rates.

Conclusion There are varying symptoms of band erosion. Those such as weight regain, nonspecific epigastric pain, and vomiting are less severe, but more serious complications include bowel obstruction and acute bleeding of the upper gastrointestinal tract. Because some patients show only nonspecific symptoms, the erosion rate is assumed to be higher than reported [12, 24, 36, 54]. The increasing incidence during long-term follow-up has not yet been

55

well described [41, 50, 52]. Through long-term follow-up, researchers need to investigate whether the advantages of the low-pressure bands also result in a decreased erosion rate. In addition, the relevance of band manometry should be investigated in studies [44]. Patient-related factors such as the intake of nonsteroidal anti-inflammatory drugs, bronchospasmolytic drugs, and anticoagulant substances must be included in data analysis and further studies. Band migration should be treated according to symptomatology and the patient’s specific condition. In our opinion, the higher incidence of band migration after intraoperative gastric perforation is a contraindication to replacing a new gastric band after band removal because of erosion [34]. In this case, conversion to either Roux-en-Y gastric bypass or biliopancreatic diversion is recommended [32]. Furthermore, there are no data in the literature on specific criteria that would allow us to select patients, either for restrictive or malabsorptive procedures, to improve final outcomes. To guarantee long-term success after bariatric surgery and to avoid complications, particularly following combined procedures, lifelong postoperative care is required; this is a specific peculiarity of obesity surgery. Because only low-level evidence is available, based on limited long-term follow-up data obtained in a few single-centre studies, prospective research enrolling all patients is indicated. This is being done by the German multicenter observational study for quality assurance in obesity surgery. In this study, weight reduction, amelioration of comorbidities, and long-term complications are registered annually as parameters that assess daily practice in the surgical treatment of morbid obesity in Germany [44].

References 1. Ablassmaier B, Opitz I, Jacobi CA, Müller JM. Intragastrale Penetration eines justierbaren Magenbandes. Chirurg 2001; 72:838–43 2. Abu-Abeid S, Zohar DB, Sagie B, Klausner J. Treatment of intra-gastric band migration following laparoscopic banding. Safety and feasibility of simultaneous laparoscopic band removal and replacement. Obes Surg 2005; 15:849–52

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Chapter 55 · Complications After Gastric Banding–Results in Germany

3. Angrisani I, Furbetta F, Doldi Sl, et al. Lap Band adjustable gastric banding system: the Italian experience with 1,863 patients operated on 6 years. Surg Endosc 2003; 17:409–12 4. Angrisani L, Di Lorenzo N, Favretti F, Furbetta F, Iuppa A, Doldi SB, Paganelli M, Basso N, Lucchese M, Zappa M, Lesti G, Capizzi FD, Giardiello C, Paganini A, Di Cosmo L, Veneziani A, Lacitignola S, Silecchia G, Alkilani M, Forestieri P, Puglisi F, Gardinazzi A, Toppino M, Campanile F, Marzano B, Bernante P, Perrotta G, Borrelli V, Lorenzo M; Italian Collaborative Study Group for LAP-BAND. The Italian Group for LAP-BAND: predictive value of initial body mass index for weight loss after 5 years of follow-up. Surg Endosc 2004; 18:1524–7 5. Baldinger R, Mluench R, Steffen R, Ricklin TP, Riedtmann HJ, Horber FF. Conservative management of intragastric migration of Swedish adjustable gastric band by endoscopic retrieval. Gastrointest Endosc 2001; 53:98–101 6. Balsiger BM, Ernst D, Giachino D, Bachmann R, Glaettli A. Prospective evaluation and 7-year follow-up of Swedish adjustable gastric banding in adults with extreme obesity. J Gastrointest Surg 2007; 11:1470–6; discussion 1446–7 7. Belachew M, Belva PH, Desaive C. Long-term results of laparoscopic adjustable gastric banding for treatment of morbid obesity. Obes Surg 2002; 12:564–8 8. Buchwald H, Avidor Y, Braunwald E, Jensen M, Pories W, Fahrbach K, Schoelles K. Bariatric surgery. A systematic review and meta-analysis. JAMA 2004; 14:1724–37 9. Buchwald H. Consensus conference statement. Bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. Surg Obes Relat Dis 2005; 1:371–81 10. Chapman AE, Kiroff G, Game P, Forster B, O’Brien P, Ham J, Maddern GJ. Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic literature review. Surgery 2004; 135:326–51 11. Chevallier JM, Zinzindohoue F, Douard R, Blanche JP, Berta JL, Altman JJ, Cugnenc PH. Complications after laparoscopic adjustable gastric banding for morbid obesity: experience with 1000 patients over 7 years. Obes Surg 2004; 14:407–14 12. Chousleb E, Szomstein S, Lomenzo E, Higa G, Podkameni D, Soto F, Zundel N, Rosenthal R. Laparoscopic removal of gastric band after early gastric erosion: case report and review of the literature. Surg Laparosc Endosc Percutan Tech 2005; 15:24–7 13. Ceelen W, Walder J, Cardon A, Van Renterghem K, Hesse U, El Malt M, Pattyn P. Surgical treatment of severe obesity with a low-pressure adjustable gastric band: experimental data and clinical results in 625 patients. Ann Surg 2003; 237:10–6 14. Coskun H, Bozbora A, Ogunc G, Peker Y. Adjustable gastric banding in a multicenter study in Turkey. Obes Surg 2003; 13:294–6 15. DeJonge I, Tan G., Oostenbroek R. Adjustable silicone gastric banding a series with three cases of band erosion. Obes Surg 2000; 10:26–32 16. Deitel M. Overweight and obesity worldwide now estimated to involve 1.7 billion people. Obes Surg 2003; 13:329–330

17. Doldi SB, Michellotto G, Lattuada E, Zappa MA, Bona D, Sonico U. Adjustable gastric banding: 5-year experience. Obes Surg 2000; 10:171–3 18. Faretti F, Segato G, Ashton D, Busetto L, De Luca M, Mazza M, Coloni A, Banzato O, Calo E, Enzi G. Laparoscopic adjustable gastric banding in 1,791 consecutive obese patients: 12-year results. Obes Surg 2007; 17(2):168–75 19. Forsell P, Hallerbeack B, Glise H, Hellers G. Complications following Swedish adjustable gastric banding: a long term follow-up. Obes Surg 1999; 9:11–6 20. Fried M, Miller K, Kormanova K. Literature review of comparative studies of complications with Swedish Band and Lap-Band. Obes Surg 2004; 14:256–60 21. Gustavsson S, Westling A. Laparoscopic adjustable gastric banding: complications and side effects responsible for the poor long-term outcome. Semin Laparosc Surg 2002; 9(2):115–24 22. Holéczy P, Novák P, Králová A. 30% complications with adjustable gastric banding: what did we do wrong? Obes Surg 2001; 11:748–51 23. International Obesity Task Force. Call for Obesity review as overweight numbers reach 1,7 billion. London, England: International Obesity Task Force, 2003. Available at http://iotf. org.media/iotfmar17.htm. Accessed 12 September 2004 24. Klaiber C, Metzger A, Forsell P. Laparoskopisches gastric banding. Chirurg 2000; 71:146–151 25. Keidar A, Carmon E, Szould A, Abu-Abeid S. Port complications following laparoscopic adjustable gastric banding for morbid obesity. Obes Surg 2005; 15:361–5 26. Lattuada E, Zappa MA, Mozzi E, Fichera G, Granelli P, De Ruberto F, Antonini I, Radaelli S, Roviaro G. Band erosion following gastric banding: how to treat it. Obes Surg 2007; 17(3):329–33 27. Martikainen T, Pirinen E, Alhava E, Poikolainen E, Paakkonen M, Uusitupa M, Gylling H. Long-term results, late complications and quality of life in a series of adjustable gastric banding. Obes Surg 2004; 14:648–54 28. Meir E, Van Baden M. Adjustable silicone gastric banding and band erosion: personal experience and hypotheses. Obes Surg 1999; 9:191–3 29. Micheletto G, Roviaro G, Lattuada E, Zappa MA, Mozzi E, Perrini M, Lanni M, Francese M, Librenti MC, Doldi SB. Adjustable gastric banding for morbid obesity. Our experience. Ann Ital Chir 2006; 77(5):397–400 30. Miller K, Höller E, Hell E. Gastrorestriktive Operationstechniken zur Behandlung der morbiden Adipositas–Vertikale bandverstärkte Gastroplastik vs. Bandverstellbare Gastroplastik. Zentralbl Chir 2002; 127:1038–43 31. Mittermair RP, Aigner F, Nehoda H. Results and complications after laparoscopic adjustable gastric banding in super-obese patients, using the Swedish band. Obes Surg 2004; 14:1327–30 32. Mognol PM. Laparoscopic gastric bypass after failed restrictive bariatric procedures: 118 patients. Obes Surg 2005; 15:939 33. Niville E, Dams A, Vlasselaers J. Lap-band erosion: incidence and treatment. Obes Surg 2001; 11:744–747

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34. Niville E. Results of lap-rebanding procedures after lapband removal for band erosion–a mid- to long-term study. Obes Surg 2005; 15:936 35. Nocca D, Frering V, Gallix B, de Seguin des Hons C, Noël P, Foulonge MA, Millat B, Fabre JM. Migration of adjustable gastric banding from a cohort study of 4236 patients. Surg Endosc 2005; 19:947–50 36. O’Brien PE. Weight loss and early and late complications– the international experience. Am J Surg 2002; 184:42S– 45S 37. Ren CJ, Weiner M, Allen JW. Favorable early results of gastric banding for morbid obesity: the American experience. Surg Endosc 2004; 18:543–6 38. Sauerland S, Angrisani L, Belachew M, Chevallier JM, Favretti F, Finer N, Fingerhut A, Garcia Caballero M, Guisado Macias JA, Mittermair R, Morino M, Msika S, Rubino F, Tacchino R, Weiner R, Neugebauer EAM. Obesity surgery. Evidence-based guidelines of the European Association for Endoscopic Surgery. Surg Endosc 2005; 19:200–21 39. Schouten R, van Dielen FM, Greve JW. Re-operation after laparoscopic adjustable gastric banding leads to a further decrease in BMI and obesity-related co-morbidities: results in 33 patients. Obes Surg 2006; 16:821–8 40. Silecchia G, Restuccia A, Elmore U, Polito D, Perotta N, Genco A, Bacci V, Basso N. Laparoscopic adjustable silicone gastric banding. Prospective evaluation of migration of the lap-band. Surg Laparosc Endosc Percutan Tech 2001; 11:229–234 41. Silecchia G, Perrotta N, Boru C, Pecchia A, Rizzello M, Greco F, Genco A, Bacci V, Basso N. Role of a minimally invasive approach in the management of laparoscopic adjustable gastric banding postoperative complications. Arch Surg 2004; 139:1225–30 42. Spivak H, Hewitt MF, Onn A, Half EE. Weight loss and improvement of obesity-related illness in 500 U.S. patients following laparoscopic adjustable gastric banding procedure. Am J Surg 2005; 189:27–32 43. Steffen R, Biertho L, Ricklin T, Piec G, Horber F. Laparoscopic adjustable gastric banding: a five year prospective study. Obes Surg 2003; 13:404–11 44. Stroh C, Hohmann U, Arnold F, Manger T. Bandmigration– eine Spätkomplikation nach Gastric Banding. Chirurg 2005; 76:689–95 45. Stroh C, Hohmann U, Schramm H, Manger T. Long term results after gastric banding. Zentralbl Chir 2005; 130:410–8 46. Stroh C, Manger T. [Complications after adjustable gastric banding. Results of an inquiry in Germany]. Chirurg 2006; 77(3):244–50 [German] 47. Stroh C, Manger T. Studie zur operativen Therapie der Adipositas–Aufruf zur Teilnahme. Deutsche Gesellschaft für Chirurgie–Mitteilungen 2004; 4:389–91 48. Suter M, Bettschart V, Giusti V. A 3 year experience with laparoscopic gastric banding for morbid obesity. Surg Endosc 2000; 14:532–6 49. Suter M. Laparoscopic band repositioning for pouch dilatation/slippage after gastric banding: disappointing results. Obes Surg 2001; 11:507–12

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50. Suter M, Guisti V, Heraief E, Calmes JM. Band erosion after laparoscopic gastric banding. Occurrence and results after conversion to roux-en-Y gastric bypass. Obes Surg 2004; 14:381–6 51. Suter M, Giusti V, Worreth M, Heraif E, Calmes J. Laparoscopic gastric banding. A prospective randomized study comparing the Lap-band and the SAGB: early results. Ann Surg 2005; 1:55–62 52. Suter M, Calmes JM, Paroz A, Giusti V. A 10-year experience with laparoscopic gastric banding for morbid obesity: high long-term complication and failure rates. Obes Surg 2006; 16:829–35 53. Szould A, Abu-Abeid S. Laparoscopic adjustable silicone gastric banding for morbid obesity: results and complications in 715 patients. Surg Endosc 2002; 16:230–3 54. Taskin M, Kagan Z, Ethem U. Intraluminal duodenal obstruction by a gastric band following erosion. Obes Surg 2001; 11:90–2 55. Vantienen B, Vandeerweg W, D`Hoore A. Intragastric erosion of laparoscopic adjustable silicone gastric band. Obes Surg 2000; 10:474–6 56. Vertruyen M, Paul G. 11-cm Lap-Band system placement after history of intragastric migration. Obes Surg 2003;13:435–8 57. Weiss H, Nehoda HD, Labeck B, Peer R, Aigner F. Gastroscopic band removal after intragastric migration of adjustable gastric band: a new minimal invasive technique. Obes Surg 2000; 10:167–70 58. Weiner R, Wagner D, Blanco-Engert R, Bockhorn H. Eine neue Technik zur laparoskopischen Platzierung des steuerbaren Magenbandes (LAP-Band) zur Vermeidung eines Slippage. Chirurg 2000; 71:1243–50 59. Weiner R, Blanco-Engert R, Weiner S, Matkowitz R, Schäfer L, Pomhoff I. Outcome after laparoscopic adjustable gastric banding–8 years experience. Obes Surg 2003; 13:427–34 60. Westling A, Bjurling K, Öhrvall M, Gustavson S. Silicone adjustable gastric banding. Disappointing results. Obes Surg 1998; 8:467–74 61. Wolff S. Magenbandpenetration–eine schwerwiegende Komplikation nach Gastric Banding? Zentralbl Chir 2002; 127:1086–90 62. World Health Organization. World Health Report 2002. Available at http://www.iotf.org. Accessed 13 January 2004 63. Worldwatch Institute. Available at http://www.worldwatch.org. Accessed 9 September 2002 64. Zehetner J, Holzinger F, Triaca H, Klaiber C. A 6-year experience with Swedish adjustable gastric band. Prospective long-term audit of laparoscopic gastric banding. Surg Endosc 2004; 11:S0930–2794 65. Zinzindohoue F, Chevallier JM, Douard R, Elian N, Ferraz JM, Blanche JP, Berta JL, Altman JJ, Safran D, Cugnenc PH. Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid obesity: prospective study of 500 consecutive patients. Ann Surg 2003; 237:1–9

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Chapter 55 · Complications After Gastric Banding–Results in Germany

Discussion Gryska: Having a look at a reoperation rate of

55

30%, do you think we should look at gastric banding as something we should do or should not do anymore? Stroh: That is a big discussion. In Europe, the situation is that the rate of gastric banding performed is decreasing more and more. And malabsorptive procedures are increasing. But in the States, it is quite different at the moment, because after the FDA approval, bandings are performed more and more. But you should be careful having a look at the European data. Franz: You are right. In my hospital I am required to report every explantation and the reason why I do so. This is a medical–legal protection for the hospital. Are you required in Germany to report explantations to somebody? Stroh: No. That is a very big problem in Germany. And a very big problem for the insurance system as well. Franz: Bruce. Do you have to report? Ramshaw: Not at this point. The biggest question is, who is going to fund this collection? Chowbey: What approach do you use for placement of the band? Stroh: We are using the pars flaccida technique. Chowbey: But most of the studies you showed used the perigastric approach. Stroh: This is why it is really difficult to show if this complication is really increasing or just a complication of an approach which nobody uses anymore. We know that slippage is decreasing, and we know that pouch dilatation is decreasing, but we really do not know if migrating is really decreasing. So we have used the pars flaccida technique since 2000, and band migration is occurring after 10 years. So we really do not know today if this complication is really decreasing as well. Chowbey: In India we are moving away from the band because we saw that 25–35% of the patients need further operations or explantation of the band. Bringman: I work in Stockholm, where gastric banding was invented, and we almost stopped using it due to its complications. Another comment is that concerning registration of obesity surgery,

we just started a register, and we hopefully will have some answers in a few years. Schumpelick: Thank you very much for the comment. Klinge: Are there any analyses using Kaplan–Meier curves showing the cumulative incidence rates of complications? The reason is that, as in incisional hernia, we know that the means given in the literature have to at least be doubled over the long term. Schumpelick: You presented the data to the German Surgical Society. What was the reaction? Stroh: Moving away from the band.

56

Alloplastic Implants for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse T. Kavvadias, U. Klinge, B. Schuessler

440

Chapter 56 · Alloplastic Implants for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse

Introduction

56

Stress urinary incontinence (SUI) is the complaint of involuntary leakage with effort or exertion or with sneezing or coughing [1]. Urethral hypermobility, which permits urethral opening during stress, as well as insufficiency of the urethral sphincter seem to be the two main contributing factors that lead to the above mentioned symptoms [2]. Pelvic organ prolapse (POP)–which is defined as protrusion of the anterior vaginal wall, the vaginal cuff, and the posterior vaginal wall, thus including the bladder, enterocele, or rectum– often shows a strong correlation with lower urinary tract symptoms in women [3]. Apart from the objective findings, symptoms of POP are heaviness, a dragging sensation, and the need to digitally replace the prolapse in order to defecate or micturate [1]. POP development is multifactorial; vaginal childbirth, advancing age, and increased body mass index seem to be the most consistent risk factors [4]. The measured prevalence of urinary incontinence varies widely among different populations and age groups and is very sensitive to how the survey was conducted and whether urodynamics were performed. Reports of »any« incontinence or »at least once in the past 12 months« are estimated to apply to 25–45% of adult women, and SUI has a percentage of 50% [5]. The prevalence of POP seems to be around 29% of the female population, according to the presence of symptoms [6]. Apart from the obvious high prevalence of SUI and POP, they both have a significant impact on a woman’s quality of life [2]. The symptoms affect a woman’s everyday life in many ways, including decreased physical and sexual activity, diminished social and self-confidence, and low overall quality of life and sense of well-being. Today, surgery is the most promising and effective therapy for both SUI and POP, showing high rates of subjective and objective cure and strong improvement in terms of quality of life. Lately there is an ongoing tendency to use meshes in the surgical treatment of SUI and POP, with the development of the »perfect« material and technique being in focus. This chapter presents an overview of mesh surgery in urogynecology (SUI

and POP) with special emphasis on the advantages and unresolved issues.

Meshes in Stress Urinary Incontinence Abdominal colposuspension was the procedure of choice for surgical management of SUI until 1995, when Ulmsten and Petros introduced the intravaginal slingplasty using polypropylene mesh, a procedure that was received with great enthusiasm because of its simplicity and short operating time [7]. In a controlled randomized trial, this procedure was shown to have no inferiority in terms of efficacy as well as in the long term. Success rates reach 81%. Furthermore, it is advantageous in terms of fewer postoperative complications and less recovery time compared with colposuspension [8]. However, although well manageable, bladder injury caused by insertion of the trocar is more common when using the sling procedure [9]. At present, the gold standard in SUI surgery is the suburethral sling, using either the tensionfree vaginal tape (TVT) or the transobturator tape (TOT) technique (⊡ Fig. 56.1). The two procedures do not seem to differ in terms of efficacy, with TOT being advantageous because of the lower rate of bladder injuries [10]. The initial concern that the meshes used might lead to high rates of erosion did not hold true when macroporous polypropylene was used. In two long-term trials, the erosion rate was 1.7% and 3.1%, respectively. Most of the erosion was into the vagina [9, 11], whereas erosion into the urethra or bladder was more or less anecdotal [12]. However, low erosion rates in SUI depend on the selection of material. A prospective randomized controlled trial by Meschia et al. showed that vaginal erosion of the Amid type III mesh used for intravaginal slingplasty was as high as 9% in a 2-year follow-up, which is significantly higher compared to 0% using the classical TVT (type I macroporous, monofilament, polypropylene mesh) in the same trial [13]. This was supported by Baessler et al., who showed a series of major complications, including erosion of this type of mesh, in a case series of 19 women treated with intravaginal slingplasty [14].

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⊡ Fig. 56.1. Routes for transobturator and retropubic slings

⊡ Fig. 56.2. Removal of an eroded transobturator Safyre sling after dislocation of the right silicone arm under the vaginal mucosa

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The use of silicone also seems to increase erosive complications. Kuschel et al. demonstrated dislocation of the silicone column of the TOT-Safyre, a composite sling consisting of a macroporous polypropylene mesh beneath the urethra and two silicone arms anchoring the sling. The erosion rate reached a percentage of 8.8%, mainly as a result of dislocation of the silicone arm from its lateral position beneath the vaginal mucosa (⊡ Fig. 56.2) [15]. With ongoing research and further development of existing macroporous materials, incidents such as the »rolling effect« of the suburethral sling are more or less under control. However, inflammatory reaction around the mesh cannot be avoided. Macrophage accumulation around the filaments of the tape, cellular proliferation, and changes in collagen composition are present in the vaginal wall, identical to the reaction found in the abdominal wall after hernia mesh surgery (⊡ Fig. 56.3) [16]. Although erosion is not a major complication all in all, development of the right material is still an issue. Overall, the properties and requirements of the sling material that might guarantee high success rates combined with fewer complications can be defined as follows: pore size >1 mm, little elasticity (<10%), and width ≥1 cm to prevent cutting through the urethra under load. The tensile strength must not necessarily be >2 N/cm, and the tension by application should not exceed 3–5 kPa; this limitation could eventually be objectified by future intraoperative measurements. The biological properties of the mesh should guarantee minimal inflammation and fibrosis with little white cell turnover and little shrinkage. Sharp-ending fibers must be avoided because they may stimulate the inflammatory response. Nonabsorbable, permanent, and synthetic materials should be preferred instead of collagen devices [17].

Meshes in Pelvic Organ Prolapse

⊡ Fig. 56.3. Accumulation of macrophages around the filaments of a polypropylene mesh (suburethral sling)

Besides conservative options such as vaginal pessaries and physiotherapy, surgery is the mainstay of POP treatment. Surgery in prolapse is a threetarget issue: (1) control of prolapse, (2) control or avoidance of problems related to bladder and

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Chapter 56 · Alloplastic Implants for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse

bowel function, and (3) restoration or improvement of cohabitation, without new dyspareunia either for the female patient or her male partner. Basically, there are two different approaches: (1) transvaginal fixation of the vaginal cuff without mesh and (2) abdominal cuff fixation with mesh, which is necessary to bridge the vaginal cuff for fixation at the hollow of the sacrum. In a Cochrane review, Maher et al. compared the surgical routes used in pelvic surgery. They found that the vaginal approach offers less surgery time, a quicker return to activities, and lower costs; the abdominal approach showed lower recurrence rates and less dyspareunia, at the expense of a mean erosion rate of 3.2% [18]. Therefore, vaginal mesh techniques might be able to combine the advantages of both procedures: less surgery time, a quicker return to activities, and lower costs from the traditional vaginal approach and low recurrence and dyspareunia rates from the abdominal route. Based on this, numerous vaginal self-anchoring mesh »kits« have been introduced, all using lightweight macroporous mesh. The results today are derived primarily from the Apogee and Perigee systems as well as the Prolift system. Surprisingly, the results in terms of mesh erosion (⊡ Fig. 56.4), dyspareunia, and pain so far do not meet the expectations of many experts in this field.

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⊡ Fig. 56.4. Mesh erosion on the anterior vaginal wall

Hiltunen et al. (2008), in a randomized controlled trial that included 202 women and used the Sofradim mesh, reported an erosion rate of 17% and a recurrence rate of 6.7% in a 12-month follow-up [19]. Collinet et al. [20] and AbdelFattah et al. [21] reported high erosion rates of 12.2% and 10%, respectively, using the Prolift mesh. Altman et al., using the same material and a follow-up time of 2 months, reported an erosion rate of 1.6% but a higher recurrence rate of 13% [22]. In the same study, pelvic pain was up to 5.2%. Many of the studies have not yet reported on dyspareunia, although in an observational study of Tayrac et al., this problem reached a percentage of 12.8% [23].

Unresolved Issues and Prevention Strategies In summary, there are three different problems related to the mesh kits in use today: erosion, pain, and dyspareunia, and all three result from the implanted mesh. As far as erosion is concerned, the fact that the same material used in the abdominal approach shows better results indicates that it is not just the material that causes mesh complications but, apparently, the route of application. This is substantiated by previous data from Wu et al., who showed that the erosion rate for abdominal sacrocolpofixation increases when the mesh is introduced through the vagina [24]. Furthermore, this is supported by an analysis of results and changes in surgical strategy by Collinet et al., who showed that minimizing vaginal incision may lead to a reduction in erosion [20]. Another unresolved issue is that of the mesh as a pain initiator, particularly pain in the muscles adjacent to the sacrum. One possible cause could be the anchoring of the mesh in the pelvic muscles. One solution might be to replace nonabsorbable anchoring arms with absorbable material. Dyspareunia is based on erosion (especially if the partner has the problem) as well as mesh shrinkage and the muscle pain caused by the anchoring arms. Recent guidelines recommending avoidance of vaginal mesh kits in sexually active

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women do not seem to be a valid solution, as this would exclude the majority of patients [25]. In essence, because the rationale for the use of mesh kits is intact, further developments in mesh and anchoring material are needed, as well as a better understanding of the vaginal wall reaction to polypropylene meshes, especially regarding why a small mesh surface, as used in TVT/TOT, shows a behavior different from that of large surfaces of the same material.

References 1. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck, Victor A, Wein A. Standardisation Sub-Committee of the International Continence Society. The standardisation of terminology in lower urinary tract symptoms; report from the standardisation sub-committee of the International Continence Society. Urology 2003;61(1):37–49 2. Abrahams P, Cardozo L, Khoury S, Wein A. Incontinence. Health Publications, Plymouth, UK, 2005 3. Buchsbaum GM. Urinary incontinence and pelvic organ prolapse, Minerva Urol Nefrol 2006;58(4):311–19 4. Jelovsek J, Maher C, Barber M. Pelvic organ prolapse. Lancet 2007 24;369(9566):1027–38 5. Minassian V, Drutz H, Al-Badr A. Urinary incontinence as worldwide problem. Int J Gynaecol Obstet 2003;82(3): 327–38 6. Barber M, Neubauer N, Klein-Olarte V. Can we screen for pelvic organ prolapse without a physical examination in epidemiologic studies? Am J Obstet Gynecol 2006;195(4):942–8 7. Ulmsten U, Petros P. Intravaginal slingplasty: an ambulatory surgical procedure for treatment of female urinary incontinence. Scand J Urol Nephrol 1995;29(1):75–82 8. Ward K, Hilton P; UK and Ireland TVT Trial Group. Tension-free vaginal tape versus colposuspension for primary urodynamic stress incontinence: 5-year follow up. BJOG 2008;115(2):226–33 9. Ward K, Hilton P; UK and Ireland TVT Trial Group. Prospective multicenter randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence. BMJ 2002;325(7355):67 10. Freeman R, Holmes D, Smith P, Hillard T, Yang Q, Agur W, Abrams P. Is transobturator tape (TOT) as effective as tension-free vaginal tape (TVT) in the treatment of women with urodymamic stress urinary incontinence? Results of a multicentric RTC [ICS abstract]. Neurourol Urodyn 2008;27(7):573–4 11. Kuuva N, Nilsson C. Long-term results of the tension-free vaginal tape operation in an unselected group of 129 stress incontinent women. Acta Obstet Gynecol Scand 2006;85(4):482–7

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12. Werner M, Najjari L, Schuessler B. Transurethral resection of tension-free vaginal tape penetrating the urethra. Obstet Gynecol 2003;102(5 Pt 1):1034–6 13. Meschia M, Pifaroti P, Bernasconi F, Magatti F, Vigano R, Bertozzi R, Barbacini P. Tension free vaginal tape and intravaginal slingplasty for stress urinary incontinence: a multicenter randomised trial. Am J Obstet Gynecol 2007; 195(5):1338–42 14. Baessler K, Hewson A, Tunn R, Schuessler B, Maher C. Severe mesh complications following intravaginal slingplasty. Obstet Gynecol 2005;106(4):713–6 15. Kuschel S, Schuessler B. Results on function and safety of the Safyre-t, a hybrid transobturator vaginal sling for the treatment of stress urinary incontinence. Neurourol Urodyn 2008;27(5):403–6 16. Kavvadias T, Kaemmer D, Klinge U, Kuschel S, Schuessler B. Foreign body reaction in vaginally eroded and non eroded polypropylene tension free sub-urethral tapes in the human female: a case series. In: Abstracts from the 33rd Annual Meeting of the International Urogynecological Association 2008;19(Suppl 1):13 17. Klinge U, Binneboessel M, Kuschel S, Schuessler B. Demands and properties of alloplastic implants for the treatment of stress urinary incontinence. Expert Rev Med Devices 2007;4(3):349–59 18. Maher C, Baessler K. Glazener C, Adams E, Hagen S. Surgical management of pelvic organ prolapse in women. Cochrane Database Syst Rev 2004 18;(4):CD004014 19. Hiltunen R, Nieminen K, Takala T, Heiskanen E, Merikari M, Niemi K, Heinonen P. Low-weight polypropylene mesh for anterior vaginal wall prolapse: a randomized controlled trial. Obstet Gynecol 2007;110(2 Pt 2):455–62 20. Collinet P, Belot F, Debodinance P, Ha Duc E, Lucot J, Cosson M. Transvaginal mesh technique for pelvic organ prolapse repair: mesh exposure management and risk factors. Int Urogynecol J Pelvic Floor Dysfunct 2006;17(4):315–20 21. Abdel-Fattah M, Ramsey I, West of Scotland Study Group. Retrospective multicentre study of the new minimally invasive mesh repair devices for pelvic organ prolapse. BJOG 2008;115(1):22–30 22. Altman D, Vayrynen T, Engh M, Axelsen S, Falconer C, Nordic Transvaginal Mesh Group. Short-term outcome after transvaginal mesh repair of pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2008;19(6):787–93 23. de Tayrac, Devoldere G, Renaudie J, Villard P, Guilbaud O, Eglin G, French Ugytex Study Group. Prolapse repair by vaginal route using a new protected low-weight polypropylene mesh: 1 year functional and anatomical outcome in a prospective multicentre study. Int Urogynecol J Pelvic Floor Dysfunct 2007;18(3):251–6 24. Wu J, Wells E, Hundley A, Connolly A, Williams K, Visco A. Mesh erosion in abdominal sacral colpopexy with and without concomitant hysterectomy. Am J Obstet Gynecol 2006;194(5):1418–22 25. Konsensuspapier der Operateure der Prolift-Trainingszentren. Empfehlungen zur Rekonstruktion von Beckenbodendefekten mit Prolift. Gynaekologie Aktuell; Ein Supplement zum Frauenarzt, April 2008

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Discussion

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Kukleta: Well, I was wondering when the TVT was coming up so that you do not have more infections. Because we would probably never implant a mesh under conditions as you do. Schüssler: We also wonder about that. But infection is not a problem at all. Fitzgibbons: You said that the infection rate is very low but erosions are high. In our way of thinking about prosthetic material, it is the same. But my comment is that this area is probably ideal for the biologicals if they can be put under tension. Schüssler: There are data out in the literature with biological materials for both prolapse and incontinence. But the results are not as good as we expected them [to be]. Klinge: I was always fascinated about the similar problems they have in the pelvic area that we have for our normal hernias. And a lot of the experiences we had, you had as well. Some years ago they tried PTFE as a band, and it failed completely. And they tried small porous meshes and had a high complication rate. So they changed to the large porous meshes. They tried biologicals and had the same problems. So there is the problem that we have, and if we look to the last talks here, the hiatal hernia, the gastric banding, and this one. The common problem of all of them is migration. Migration through tissue. And we all know the problem. In all of these diseases, we have the serious problem that if the prosthesis shows some kind of migration, we have serious problems. And therefore we have to look at what is the reason for migration on the cellular level and whether there any ideas for devices that have a higher or lower risk of migrating through tissue. So we should work together because we have the same problems. Schumpelick: But I think there are slight differences. Because we do it absolutely aseptically, and they do it with physiologic contamination. Kukleta: I know that you do not think about the tension you put on. You just pull it out and cut it off, and just the structure of polypropylene allows it to stay in place. Do you think you induce local ischemia by pressure?

Schüssler: That may happen with the TVT. But we do not have many problems with the TVT. On the other hand, if you do overtension, then the patient immediately has problems.

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Prophylactic IPOM Mesh To Prevent Parastomal Hernias D. Berger and M. Bientzle

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Chapter 57 · Prophylactic IPOM Mesh To Prevent Parastomal Hernias

Introduction After an ostomy is created, hernias are a common complication [1, 2]. Sometimes the frequency exceeds 50% after 1 year, especially if computed tomography (CT) is used diagnostically [3]. The parastomal hernia may be associated with stoma care problems and so considerably limits the social activity of the affected patient. The correct surgical technique when creating a stoma is inevitable, but surgical dogmas have not been unequivocally confirmed [1]. From a pathogenetic point of view, parastomal hernias may be comparable with incisional hernias, explaining the lacking efficacy of only technical approaches [4–7]. If disturbed collagen synthesis is accepted as the underlying problem, the use of synthetic nonabsorbable meshes is mandatory for treating and preventing hernias. From a technical point of view, prophylactic meshes can be used in ways known from therapeutic procedures. An onlay, sublay, or intraperitoneal positioning of the prophylactic mesh may be possible. Advantages of the intraperitoneal onlay mesh (IPOM) technique are its technical convenience, its easy performance by laparoscopy, and the reduced infection rate as shown for laparoscopic incisional hernia repair [8, 9]. The availability of a mesh with a central hole and a dome made of a material allowing intraperitoneal use, DynaMesh IPST (FEG-Textiltechnik, Aachen, Germany), was the precondition of a prospective observational study to evaluate the rate of parastomal hernias and other stoma-related or mesh-related complications when the mesh was prophylactically used in an intraperitoneal onlay position.

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Patients, Material, and Methods Between March 2006 and May 2008, 33 patients (14 female, 19 male) were enrolled and prospectively followed every 3 months. Thirty colostomies and three ileostomies were created. Two of these patients underwent correction of a preexisting ileostomy or colostomy. In two patients with a preexisting stoma, a colectomy with a new stoma

⊡ Table 57.1. Demographic and surgical data     

   

14 female, 19 male patients Median age: 71 years (41–86) Median body mass index: 27 (17–37) Median operating time: 153 min (90–260) 19 APRE, 12 Hartmann’s procedures (including two colectomies), two patients with only correction of a preexisting stoma 30 colostomies, three ileostomies 6/33 laparoscopic procedures 24/33 malignant diseases, 9/33 benign diseases Median follow-up: 18 months (2–28)

was necessary. The only exclusion criterion was an emergency procedure. Major contamination did not occur during the primary procedure. Demographic and surgical data are summarized in ⊡ Table 57.1. As also shown in ⊡ Table 57.1, the stomas were predominantly created because of malignant diseases. One patient suffered from ulcerative colitis, and two patients had Crohn’s disease. Other underlying diseases were otherwise untreatable severe incontinence or problems with a preexisting stoma. DynaMesh IPST represents a real mesh structure warp-knitted by polyvinylidene fluoride (PVDF) containing a small amount of polypropylene on the parietal side. It has been experimentally proven that the mesh is well incorporated and effectively prevents adhesions to the intestine. Furthermore, PVDF is associated with a reduced inflammatory response and development of fibrotic tissue compared with polypropylene or expanded polytetrafluoroethylene [10–12]. The implantation technique is easy and does not significantly prolong the procedure. In short, the stoma loop is pulled through the funnel, which is oriented to the abdominal cavity. The funnel should fit tightly. Therefore, in 32 cases, meshes with a funnel diameter of 2 cm were used. One patient received a mesh with a funnel diameter of 3 cm. The mesh is fixed only by tacks at the edges and around the stoma itself. The stoma loop itself is not fixed at the mesh. Six of 33 procedures were performed laparoscopically.

447 Chapter 57 · Prophylactic IPOM Mesh To Prevent Parastomal Hernias

Results One patient with liver metastasis of an advanced carcinoma of the sigmoid died in the early postoperative period because of hepatic failure. Two patients died after 6 and 15 months, respectively, due to advanced cancer (n=1) and liver failure during anti-inflammatory therapy of ulcerative colitis (n=1). During a median follow-up of 18 months, no parastomal hernia or stoma prolapse was detected clinically. In 15 patients, a CT scan was performed 1 year after the primary procedure, which also excluded any parastomal herniation. Stomal obstructions did not occur despite the fact that in 32 out of 33 patients, a mesh with the smallest diameter (2 cm) was used. Even in a patient with a body mass index of 38, the smallest diameter proved to be adequate without signs of obstruction. Therefore, it should be pointed out that the funnel should fit tightly around the bowel to prevent a prolapse. Meshes with larger diameters, 3 cm and even 4 cm, are available, but these need to be reserved for very obese patients with a dramatically thickened mesocolon. Primary mesh infections were not observed. Two patients developed a secondary enteral leak with peritonitis. Both patients were treated with daily planned relaparotomies and lavage. After the peritonitis had disappeared, the abdominal wall was closed, leaving the mesh in situ. In both patients the healing process proceeded uneventfully. After almost 2 years and 3 months, respectively, there are no clinical signs, elevated blood cell count, or elevated serum levels of C-reactive protein in either patient. The time needed for implantation of the prophylactic mesh was very low, never exceeding 5 min.

Discussion As outlined above, parastomal hernia is a very frequent and sometimes burdening problem for the affected patients [1, 2]. Although the repair of parastomal hernias seems to be effective today, the only technique that yields good results remains difficult and elaborate [13]. Furthermore, some

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complications are associated with parastomal hernia repair, thus strongly supporting the claim that parastomal hernias should be prevented. In 2004 a randomized study demonstrated the dramatically reduced incidence of parastomal hernias after prophylactic mesh implantation in a retromuscular position [14, 15]. Since that time, further studies have supported the view that prophylactic use of a mesh may reduce the rate of parastomal herniation [16–19]. The meshes were implanted after being incised in a sublay or onlay position. In these series, the infection rate proved to be very low, and other complications were not described. Therefore, a summary of all studies dealing with the prophylactic use of meshes to prevent parastomal herniation concluded that meshes are effective and associated with a negligible overall complication rate [20]. However, these series had in common the fact that the number of enrolled patients was low, which could explain the low rate of complications. In our study, the technique differed completely from that used in the above-mentioned studies by the intraperitoneal application of the mesh. Preference for an IPOM technique is based on the fact that it is more suitable for laparoscopic approaches. Furthermore, the preparation of different abdominal wall layers, creating large wound areas, is no longer necessary. At least for laparoscopic repair of incisional hernias, it has been clearly shown that the infection rate is lower compared with conventional techniques, which is explained by the reduced tissue trauma and the contact of the mesh with peritoneum on both sides [8, 9]. Another aspect favoring the intraperitoneal position is the possible overlap, which is much greater than in a sublay position. Sometimes the retromuscular space is quite restricted because of narrow rectus muscles. In these cases, sometimes only 2 cm of overlap is possible. The overlap of intraperitoneal positioning is limited only by the anatomical borders of the abdominal cavity. Therefore, a width of more than 5 cm is always possible, leading to wide augmentation of the abdominal wall around the stoma. The shape of the mesh used in our study provides further advantages compared with twodimensional meshes that are incised. The crossshaped incision is followed by a relevant impair-

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ment of the mesh stability. On the other hand, the funnel around the stoma loop should effectively prevent any prolapse. The main precondition, however, is the tight fitting of the funnel around the stoma loop. However, a stenosis may also be created if the funnel is too narrow. We did not experience any stenosis, but we systematically tested the outlet digitally at the end of the procedure. A further aspect sometimes raised is the risk of infection if the contaminated end of the stoma loop is pulled through a mesh. In our series at least, there was no primary infection, and the literature does not support that potential risk. On the contrary, the infection rate published today is astonishingly low [20]. The described course of two patients with severe septic complications clearly showed that the combination of the intraperitoneal position and PVDF as the mesh material effectively reduces the susceptibility to persistent mesh infections. In conclusion, the prophylactic use of DynaMesh IPST to prevent parastomal hernias shows promising results. No complications occurred during a median follow-up of 18 months. In particular, infectious complications were not observed. The procedure can be easily performed laparoscopically as well as in conventional surgery for permanent terminal colostomies and ileostomies.

References

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1. Carne PW, Robertson GM, Frizelle FA (2003) Parastomal hernia. Br J Surg 90:784–793 2. Israelsson LA (2008) Parastomal hernias. Surg Clin North Am 88:113–125 3. Cingi A, Cakir T, Sever A, Aktan AO (2006) Enterostomy site hernias: a clinical and computerized tomographic evaluation. Dis Colon Rectum 49:1559–1563 4. Klinge U, Si ZY, Zheng H, Schumpelick V, Bhardwaj RS, Klosterhalfen B (2001) Collagen I/III and matrix metalloproteinases (MMP) 1 and 13 in the fascia of patients with incisional hernias. J Invest Surg 14:47–54 5. White B, Osier C, Gletsu N, Jeansonne L, Baghai M, Sherman M, Smith CD, Ramshaw B, Lin E (2007) Abnormal primary tissue collagen composition in the skin of recurrent incisional hernia patients. Am Surg 73:1254–1258 6. Rosch R, Junge K, Knops M, Lynen P, Klinge U, Schumpelick V (2003) Analysis of collagen-interacting proteins in patients with incisional hernias. Langenbecks Arch Surg 387:427–432

7. Kasperk R, Willis S, Klinge U, Schumpelick V (2002) Update on incisional hernia. Parastomal hernia. Chirurg 73:895–898 8. Pierce RA, Spitler JA, Frisella MM, Matthews BD, Brunt LM (2007) Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual. Surg Endosc 21:378–386 9. Carlson MA, Frantzides CT, Shostrom VK, Laguna LE (2008) Minimally invasive ventral herniorrhaphy: an analysis of 6,266 published cases. Hernia 12:9–22 10. Klinge U, Klosterhalfen B, Ottinger AP, Junge K, Schumpelick V (2002) PVDF as a new polymer for the construction of surgical meshes. Biomaterials 23:3487–3493 11. Conze J, Junge K, Wei BC, Anurov M, Oettinger A, Klinge U, Schumpelick V (2008) New polymer for intra-abdominal meshes–PVDF copolymer. J Biomed Mater Res B Appl Biomater 87(2):321–328 12. Junge K, Binnebosel M, Rosch R, Jansen M, Kammer D, Otto J, Schumpelick V, Klinge U (2009) Adhesion formation of a polyvinylidenfluoride/polypropylene mesh for intra-abdominal placement in a rodent animal model. Surg Endosc 23(2):327–333 13. Berger D, Bientzle M (2007) Laparoscopic repair of parastomal hernias: a single surgeon’s experience in 66 patients. Dis Colon Rectum 50:1668–1661 14. Jänes A, Cengiz Y, Israelsson LA (2004) Randomized clinical trial of the use of a prosthetic mesh to prevent parastomal hernia. Br J Surg 91:280–282 15. Janes A, Cengiz Y, Israelsson LA (2004) Preventing parastomal hernia with a prosthetic mesh. Arch Surg 139:13561358 16. Marimuthu K, Vijayasekar C, Ghosh D, Mathew G (2006) Prevention of parastomal hernia using preperitoneal mesh: a prospective observational study. Colorectal Dis 8:672–675 17. Gogenur I, Mortensen J, Harvald T, Rosenberg J, Fischer A (2006) Prevention of parastomal hernia by placement of a polypropylene mesh at the primary operation. Dis Colon Rectum 49:1131–1135 18. Israelsson LA (2005) Preventing and treating parastomal hernia. World J Surg 29:1086–1089 19. Nagy A, Kovacs T, Bognar J, Mohos E, Loderer Z (2004) Parastomal hernia repair and prevention with PHSL type mesh after abdomino-perineal rectum extirpation. Zentralbl Chir 129:149–152 20. Helgstrand F, Gogenur I, Rosenberg J (2008) Prevention of parastomal hernia by the placement of a mesh at the primary operation. Hernia 12(6):577–582

Discussion Schumpelick: Are you not afraid of long-lasting bacteria in this field? Berger: These two patients showed that this should not be a big problem. But these are only two pa-

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tients, and we started to use it also in the emergency situation. Schumpelick: You know the study by Leber—that it will take some years. Berger: But you also know the opinion by Israelsson. In his department, he always uses a mesh even in the contaminated situations. And he uses it retromuscularly. Franz: It is outstanding. Have I heard it right? Should we place the stoma more laterally than the rectus muscle? Berger: I found a lot of papers telling us you have to perform it in the transrectal position, but I also found papers that showed that there is no difference where to place. Schippers: As far as I understand, you use your technique for permanent stomas. So there will be a lifelong device in the patient. Berger: Yes. Schippers: Any material you implant shows some kind of migration. How can you be sure that this will not happen to you? Berger: I cannot be sure that there will not be any kind of migration. But correction of migration in the stoma is much easier than correcting a migration, i.e. the esophagus. Schumpelick: That is an argument.

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58

Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications B. Hansson, I. de Hingh, R. P. Bleichrodt

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Chapter 58 · Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications

Introduction Parastomal herniation is a common complication of stoma formation. The incidence varies significantly and may be as high as 48% for colostomies and 28% for ileostomies (⊡ Table 58.1) [1]. The different open surgical approaches for treating parastomal hernias are shown in ⊡ Table 58.2 [1]. Stoma relocation involves relaparotomy and replacement of the stoma to the contralateral side. Besides the problem of developing an incisional hernia at the midline or at the old enterostomy site in 20–30% of cases, the technique carries a recurrence rate of up to 36.3%. Mesh repairs have a lower recurrence rate of approximately 7.8%. Unfortunately, most studies are retrospective in design and include only small numbers of patients. Therefore, it is impossible to draw definitive conclusions on

⊡ Table 58.1. Incidence of parastomal hernia [1] Parastomal hernia (%)

Follow-up

Mean

Range

Range (months)

End colostomy

15.8

4.8–48.1

35–120a

Loop colostomy

4.0

0–30.7

2.2–96a

End ileostomy

6.7

1.8–28

2.6a –9.2b

Loop ileostomy

1.3

0–6.3%

2–3.2a

a

Mean

bMedian

⊡ Table 58.2. Approaches and results of open parastomal hernia repair

58

Recurrence (%)

Follow-up

Mean

Range

Range (months)

Stoma relocation

36.3

0–76.1

15–85

Onlay mesh repair

2.9

0–33

Sublay mesh repair

a

a

a

Preperitoneal mesh repair

a

a

a

important issues such as perioperative morbidity and mortality and long-term recurrence rates after parastomal hernia mesh repair. In 2002, we described a laparoscopic technique for repairing parastomal hernias with a prosthetic mesh [2]. To provide insight into the feasibility and safety of this procedure, a prospective clinical study was started in 2002 [3]. The perioperative details and early results of the first 55 consecutive patients included in the study are presented.

Laparoscopic Repair: A Prospective Study Between 2002 and 2006, adult patients older than 18 years with a symptomatic parastomal hernia (severe pain, recurrent obstruction, poor fitting of appliance, cosmetic problems) were asked to participate in the study. The exclusion criteria were pregnancy, cardiopulmonary contraindications for laparoscopy, or life expectancy less than 2 years. Besides other information, demographic data, operative details, perioperative and postoperative complications, time to mobilization, food intake, stoma production, hospital stay, and 6-week follow-up data were recorded on a standard form.

Surgical Technique The patient is placed in a supine position. A finger condom is inserted into the stoma and fixed with a transparent adhesive drape so that a finger can be introduced into the stoma during the operation and to determine the vitality of the stoma. The surgeon and assistant stand contralateral to the stoma site. The first trocar is introduced by the open Hasson technique, and a pneumoperitoneum is created to a pressure of 12 mmHg. A 30° laparoscope is inserted, and two or three working ports are placed under direct vision on both sides of the camera. After adhesiolysis, the hernia contents are reduced. The bowel loop that runs to the stoma is identified and dissected free from the fascial edges. The hernia opening is narrowed with two nonresorbable sutures. A 15×19-cm expanded polytetrafluoroethylene patch (e-PTFE; Gore-Tex DualM-

453 Chapter 58 · Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications

esh Biomaterial, Gore & Associates, Flagstaff, AZ, USA) is fashioned with a central keyhole of 2 cm and two radial incisions of 5 mm (⊡ Fig. 58.1). This enables a funnel-like shape. The mesh is then inserted, unrolled, and tacked to the abdominal wall following the double-crown technique. The cylindrical part of the mesh forming a small collar that surrounds the stoma loop is stitched to the bowel wall.

Results Fifty-five consecutive patients fulfilled the inclusion criteria and were included in the study. Of the 55 procedures, 47 (85.5%) could be completed laparoscopically. The median operating time was 120 min. Conversion to laparotomy was indicated because of dense adhesions prohibiting safe dissection in four patients and full-thickness bowel injury in four. There was no in-hospital mortality. Postoperative recovery was uneventful in 47 patients (85%). Patients were able to consume a normal diet on day 1 (range 1–3 days), had stoma production on day 2 (range 1–13 days), and could

58

be released from the hospital on postoperative day 4 (range 2–20 days). Postoperative complications occurred in eight patients (14.4%). Four patients had to be reoperated: one for bleeding from the epigastric artery, one for a mesh infection, one for peritonitis caused by a small bowel lesion, and one for a leaking colon anastomosis. Nonsurgical complications were observed in another four patients. Follow-up at 6 weeks revealed an uneventful recovery in 51 patients (93%). Four patients reported pain at the site of the mesh. On physical examination, one recurrent parastomal hernia was diagnosed in one of the patients in whom conversion to laparotomy was performed because of a full-thickness bowel injury; the hernia was small and asymptomatic. Most wound complications had resolved. Only one residual hematoma was noted, and persisting seroma at the site of the hernia was noted in three patients. Higher incidences of conversion, intestinal damage, and reoperation occurred in the recurrent hernia group, but the number of patients was too small to reach statistical significance.

Discussion

⊡ Fig. 58.1. Keyhole repair of parastomal hernia with a sublay patch. a An expanded polytetrafluoroethylene patch (GoreTex DualMesh Biomaterial) is fashioned with a central keyhole of 2 cm and two radial incisions of 5 mm to create a funnel. b After the trephine size is narrowed with nonabsorbable sutures, the patch is positioned around the stoma and (a) fixed with staples using the double-crown technique. By overlapping the two parts of the keyhole in the patch, a funnel is created (b) around the colon (c). The patch is fixed to the colon with nonresorbable sutures

Laparoscopic parastomal hernia repair is feasible and seems to be safe since the results are similar as in open parastomal repair. However, definitive conclusions cannot be made because the experience with laparoscopic parastomal hernia repair is limited; most publications are case series of moderate quality, and long-term follow-up is lacking. Moreover, prospective randomized trials comparing open repair with laparoscopic repair are not available. Therefore, laparoscopic parastomal hernia repair cannot be advocated as the standard of care. In the literature, six series of more than five patients have been published, with 189 patients altogether [3–8]. The median number of patients in these studies is 22, ranging from nine to 66 (⊡ Table 58.3). The most frequently used techniques for parastomal hernia repair are the Sugarbaker technique (51%) and the keyhole-like technique (39%). The Sugarbaker technique is a nonslit procedure

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Chapter 58 · Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications

⊡ Table 58.3. Results of laparoscopic parastomal hernia repair in published series having more than eight patients Authors, year, design Safadi [4], 2005 Retrospective Single center

LeBlanc et al. [5], 2005 »Prospective« Single center

Hansson et al. [3], 2007 Prospective Single center

N

9

12

Age

63.5 (53–77)

? (42–89)

Technique

Sugarbaker Keyhole Other

Sugarbaker Double patch

Surgical complications

0 9

7 5

Intraoperative

Postoperative

None

Reoperated

0

Conservative Ileus

1

Reoperated Delayed rec. Ileus

1 1

Conservative Ileus Seroma Died

1 1 1

Reoperated Mesh infection Peritonitis Hemorrhage

1 2 1

Conservative Ileus Hematoma Seroma

2 5 15

Reoperated

0

Conservative Ileus Wound Infection Mesh infection Died

2 1 1 1

Enterotomy Conversion

55

63 (27–87)

Keyhole

55

Enterotomy Conversion

Mancini et al. [6], 2007 Retrospective Multicenter

25

Berger et al. [7], 2007 »Prospective« Single center

66

60 (41–85)

Sugarbaker

25

Enterotomy

1 0

5 8

1

Conversion

70 (34–92)

Sugarbaker Sandwich

41 25

Enterotomy Conversion

0 1

Reoperated Mesh infection Stoma obstruction Ileus

Followup

Recurrence

18–23

4 (44%)

20 (3–39)

1 (8%)

6 weeks

3 2

19 (2–38)

1 (4%)

24 (3–72)

8 (12.1%)

20 (8–39)

2 (10.5%)

2

Conservative ?

58

McLemore et al. [8], 2007 Retrospective Single center

19

66+12

Sugarbaker Keyhole

14 5

? Conversion

??

Reoperated Mesh infection Stoma obstruction Conservative None

2 1

455 Chapter 58 · Laparoscopic Parastomal Hernia Repair: Pitfalls and Complications

in which a mesh is used to cover the hernia opening, with an overlap of 4 cm at each side, after the stoma loop is lateralized. Lateralization may lead to retraction, tilting, and obstruction of the stoma due to bowel kinking, as was almost exclusively found in patients treated with this or a similar technique. The keyhole technique is a procedure in which the patch is draped around the bowel (⊡ Fig. 58.1). Berger developed the sandwich technique, which combines the advantages of both methods [7]. Several biomaterials such as polypropylene mesh and e-PTFE have been used for parastomal hernia repair, and most parastomal hernias can be repaired laparoscopically. The conversion rate in the literature is less than 1%, compared to 8.5% in our series of patients [3–8]. Most conversions in our series were in patients who were reoperated for a parastomal hernia. The mortality was less than 1%. The main problems associated with laparoscopic parastomal hernia repair are accidental enterotomy, postoperative ileus or stoma obstruction, mesh infection, and reherniation. In our series, 9% of patients had an accidental enterotomy. In four other series, 1.8% accidental enterotomies were reported for 112 patients altogether [4–7]. In 2007, three reviews were published about laparoscopic hernia repair [9–11]. Müller-Riemenschneider et al. [9] reported accidental enterotomies in 3% of patients who underwent laparoscopic incisional hernia repair. Pierce et al. [10] and LeBlanc et al. [11] reported an enterotomy incidence of 2.9% and 1.8%, respectively, during laparoscopic ventral and incisional hernia repair. Especially if unrecognized, bowel perforations represent a serious and potentially life-threatening complication [11]. Accidental enterotomies are recognized in 82% of cases during the first operation and are associated with a mortality of 1.7%. Eighteen percent of enterotomies are diagnosed in the postoperative period and have a significantly higher mortality of 7.7% [11]. With laparoscopy, the risk of accidental enterotomy seems to be higher than in open surgery. To prevent full-thickness bowel lesions, adhesiolysis should be performed by sharp dissection, without the use of electrocautery or ultrasonic devices. Sharp dissection has the advantage that a serosal bowel lesion can be recognized immedi-

58

ately because of local bleeding, and lesions are not sealed by electrocautery or ultrasonic devices. Stoma obstruction or (prolonged) ileus were reported in 12 (6.3%) of the 189 patients in the literature. Six patients were reoperated, three for an obstructed stoma and three for an ileus. Two patients died as a result of aspiration pneumonia, which may have been associated with bowel obstruction. Stoma obstruction is reported only in series that used the (modified) Sugarbaker technique. Probably, the lateralization and coverage of the stoma cause kinking and obstruction, especially if the prosthesis is fixed tight to the abdominal wall. Mesh infection was reported in 3.7%, similar to infection rates in laparoscopic hernia repair and lower than in open hernia repair, which may be a benefit of the laparoscopic approach [9].

References 1. Carne PWG, Robertson GM, Frizelle FA. Parastomal hernia. Br J Surg 2003; 90:784–793 2. Hansson BME, van Nieuwenhoven EJ, Bleichrodt RP. Promising new technique in the repair of parastomal hernia. Surg Endosc 2003; 17:1789–1791 3. Hansson BME, de Hingh IH, Bleichrodt, RP. Laparoscopic parastomal hernia repair is feasible and safe: early results of a prospective clinical study including 55 consecutive patients. Surg Endosc 2007; 21:989–993 4. Safadi B. Laparoscopic repair of parastomal hernias. Surg Endosc 2004; 18:676–680 5. LeBlanc KA, Bellanger DE, Whitaker JM. Laparoscopic parastomal hernia repair. Hernia 2005; 9:140–144 6. Mancini GJ, McCluskz III DA, Khaitan L, et al. Surg Endosc 2007; 21:1487–1491 7. Berger D, Bientyle M. Laparoscopic repair of parastomal hernias. A single surgeon’s experience in 66 patients. Dis Colon Rectum 2007; 50:1668–1673 8. McLemore EC, Harold KL, Efron JE, et al. Parastomal hernia short term outcome after laparoscopic and conventional repairs. Surg Innov 2007; 14(3):199–204 9. Müller-Riemenschneider F, Roll S, Friedrich M, et al. Medical effectiveness and safety of conventional compared to laparoscopic incisional hernia repair: a systematic review. Surg Endosc 2007; 21:2127–2136 10. Pierce RA, Spitler JA, Frisella MM, et al. Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of patient data accrual. Surg Endosc 2007; 21:378–386 11. LeBlanc KA, Elieson MJ, Corder JM 3rd. Enterotomy and mortality rates of laparoscopic incisional and ventral hernia repair: a review of the literature. JSLS 2007; 11(4):408– 414

59

Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration and Shrinkage J. Otto, N. Krämer, G. A. Krombach, I. Slabu, M. Hodenius, M. Baumann, U. Klinge

458

59

Chapter 59 · Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration and Shrinkage

After incorporation, textile meshes change their appearance markedly because of tissue ingrowth and integration into scar tissue. Migration and erosion, shrinkage and deformation, and fistula formation are rare but severe complications. To appreciate the clinical relevance, we have to keep in mind that 1.5 million meshes are implanted per year worldwide [1]. After mesh implantation, a significant number of patients will present to a doctor with mesh-related problems sooner or later. Among these may be either newly developed pain in the groin, functional problems in the hiatus if the mesh was placed around the oesophagus, or manifestation of fistulas to the intestines. To decide whether to monitor the complaints, surgically correct the position of the mesh, or explant the mesh, a central question must be answered: Is a dislocation of the mesh causing the current complaints? X-ray, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are the main radiological imaging methods at hand for possibly answering this question. However, X-ray is not able to show the mesh itself; only the metal surgical clips used for fixation may be visible (⊡ Fig. 59.1). With ultrasound, the mesh cannot be distinguished from the ambient structure if the mesh has been incorporated with no seroma, infection, or scar formation because the signal differences are too small to separate the mesh from the surrounding tissues (⊡ Fig. 59.2). Computed tomography and MRI struggle with the same problem: In the case of mesh incorporation with no complications, it is almost impossible to identify the mesh and reveal its exact localisation. Only in exceptional cases, if the mesh is surrounded by fluids or fat, can the fine structure of the mesh be delineated [2–4] (⊡ Fig. 59.3). Besides these exceptions, X-ray, ultrasound, CT, and MRI usually fail to directly visualise the mesh device. To achieve an MR-visible polymer device, we use superparamagnetic nanoparticles of ferrofluids [5]. These superparamagnetic iron oxides are also used as MR contrast media. On MRI, the nanoparticles cause a signal decrease by disturbing the magnetic field, resulting in a hypointense signal. A new textile mesh made from polyvinylidene fluoride with superparamagnetic particles has been

constructed (SF mesh). To compare this mesh with a conventional UltraPro mesh, they were both placed in a phantom model consisting of two pieces of meat surrounded by water to evacuate air. ⊡ Figure 59.4 shows a coronal slice of the two meshes. Only the nanoparticle-containing SF mesh

⊡ Fig. 59.1. X-ray after mesh implantation; mesh fixation with metal tacks (arrows)

⊡ Fig. 59.2. Mesh (arrow) surrounded by seroma (star)

459 Chapter 59 · Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration

could be visualised by the desired susceptibility artefacts. These artefacts enabled an increased differentiation from the tissue, which was not possible using UltraPro mesh. Based on these results, a prototype of the »visible« mesh was implanted as an inlay into the abdominal wall of a dead rat. Again, it was possible

⊡ Fig. 59.3. Computed tomographic image after mesh hiatoplasty. It is not possible to see the mesh beside the metal tacks

59

to identify and locate the mesh (⊡ Fig. 59.5) on MR images. With the aid of a dedicated small animal receiver coil and an imaging sequence providing high resolution, even the pores of the mesh could be delineated. However, this is possible only with long data acquisition. If the concentration is too high, the signal will strongly exceed the diameter of the mesh fibre. After proving that textile structures can be visualised using MRI by adding superparamagnetic particles, future work should optimise the particle size, the concentration in relation to the fibre size, and the MRI sequences. Knowledge of the magnetic properties of the mesh is important for developing models of MR signalling behaviour. On account of this, the magnetic susceptibility will be determined by superconducting interference device (SQUID) measurements. The final goal will be to find a method to image the mesh with a clear delineation of its surrounding structures. Because neither air nor susceptibility artefacts provide signals, a method to differentiate air from susceptibility artefacts with positive contrast is desirable. Such a visible mesh will be helpful both for deciding whether a revision operation of the mesh is necessary and as a tool for constructing improved

⊡ Fig. 59.4. Magnetic resonance image (MRI): Visible mesh vs. Ultrapro. No signal can be detected from the UltraPro mesh; the SF mesh causes mild signal loss (open arrow). Macroscopy: Upper arrow indicates UltraPro with blue stripes. Lower arrow indicates colourless mesh of fibres that include superparamagnetic ferroparticles (SF mesh). Both meshes were placed between air-filled plastic tubes

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Chapter 59 · Concept of Visible Mesh and Possibilities for Analysis of Mesh Migration and Shrinkage

⊡ Fig. 59.5. Magnetic resonance image of abdominal wall replacement with visible mesh in a rat model

meshes that, it is hoped, will have less shrinkage and less risk of migration, particularly for areas with a lot of mobility, such as the hiatus and the pelvic floor.

5.

Hodenius MA, Niendorf T, Krombach GA, Richtering W, Eckert T, Lueken H, Speldrich M, Gunther RW, Baumann M, Soenen SJ et al. Synthesis, physicochemical characterization and MR relaxometry of aqueous ferrofluids. J Nanosci Nanotechnol 2008, 8:2399–2409

Acknowledgements Discussion This work was supported by the German Federal Ministry of Education and Research (BMBF 01EZ 0849).

References

Schumpelick: Are you sure that every surgeon

would be glad to know where his mesh is? Otto: Probably not. Fitzgibbons: Are none of the others visible? Otto: It depends on the contrast. Just very thick

meshes in cases of seromas are able to see. 1.

2.

3.

59

4.

Junge K, Klinge U, Rosch R, Mertens PR, Kirch J, Klosterhalfen B, Lynen P, Schumpelick V. Decreased collagen type I/III ratio in patients with recurring hernia after implantation of alloplastic prostheses. Langenbecks Arch Surg 2004, 389:17–22 Crespi G, Giannetta E, Mariani F, Floris F, Pretolesi F, Marino P. Imaging of early postoperative complications after polypropylene mesh repair of inguinal hernia. Radiol Med (Torino) 2004, 108:107–115 Di MM, Runfola M, Magalini S, Sermoneta D, Gui D. Rippled mesh: a CT sign of abdominal wall ePTFE prosthesis infection. G Chir 2006, 27:384–387 Fischer T, Ladurner R, Gangkofer A, Mussack T, Reiser M, Lienemann A. Functional cine MRI of the abdomen for the assessment of implanted synthetic mesh in patients after incisional hernia repair: initial results. Eur Radiol 2007, 17:3123–3129

Schumpelick: And what about nanoparticles? Any

dangers to their use? Otto: They are already in use.

VI

VI

Strategy to Improve Results

60

Who Has the Major Role in Hernia Surgery: The Surgeon or the Material? – 463

61

Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery with Procedures Adjusted to Individual Patients – 467

60

Who Has the Major Role in Hernia Surgery: The Surgeon or the Material? R. C. Read

464

Chapter 60 · Who Has the Major Role in Hernia Surgery: The Surgeon or the Material?

Introduction Astley Cooper (1804), in the preface to his classic monograph on the anatomy and surgical treatment of hernia [1], wrote, »No disease of the human body belonging to the province of the surgeon, requires in its treatment a greater combination of accurate anatomical knowledge with surgical skill, than hernia in all of its varieties.« More recently, in 1989 George Wantz stated, »The outcome of an inguinal hernioplasty is more dependent on the skills and experience of the surgeon than on the type of repair« [2]. In 2006, Gilbert et al. [3] averred, »The use of any mesh product to repair a hernial defect will never supplant the need to fully know and utilize the layers, planes and spaces of the abdomen.« The purpose of this chapter is to document evidence supporting these judgments.

Sutured Repair

60

The importance of the surgeon’s experience in preventing recurrence after hernia repair is exemplified by the trend toward making herniology a subspecialty of general surgery. Glassow [4], in a 1970 review of 50,000 groin herniorrhaphies performed at the Shouldice Hospital, pointed out that the incidence of recurrence fell from 17% to 1% within two decades after this herniological institute was founded (1945). The improvement was attributed to modifications made to the original Shouldice procedure in the 1950s and to specialization. The first detailed analysis of the relationship between a surgeon’s operative experience of groin hernioplasty and recurrence was provided by Kingsnorth et al. in 1981 [5]. Consultants and senior registrars who had performed more than six such procedures had a 2.5% recurrence rate, whereas the figure for registrars with less experience was 9.4% (calculated to be 28% in 25 years). The authors therefore recommended careful supervision, by a consultant, of six herniorrhaphies before juniors could become principal operators. A subsequent study in 1992 [6] also involved registrars who were supervised while performing their first six Shouldice operations. Their later high recurrence rate of 4.5% was blamed on inexperience, indicat-

ing that this period of supervision was inadequate. The authors point out that at the Shouldice clinic, new staff surgeons receive close supervision for their first 50 herniorrhaphies and do not operate independently until they have repaired 100. A final assessment of their technique is made after 1,000 hernias have been operated upon. A similar finding of junior staff incurring a high incidence of early recurrence after inguinal herniotomy in children was reported by Harvey et al. [7]. Poor technique was considered to be responsible. The authors recommended that the practice of placing hernia cases at the end of the operating room list, thereby allowing junior staff to work on them unsupervised, be discontinued.

Prostheses [8] Reinforcement of sutured repairs in the groin using metallic filigrees began soon after Bassini introduced his cure (1887). During World War II, they were replaced with plastic meshes by Aquaviva and Bounet. The Lichtenstein procedure (1984), using onlay polypropylene, became the gold standard for inguinal herniorrhaphy in the 1990s. It supplanted the Shouldice operation because the recurrence rate was significantly less. Because the approach was anterior, through familiar anatomy, there seemed to be no need for a specific training period. Positioning of mesh behind the transversalis fascia is more difficult because the preperitoneal space is unfamiliar territory. The open posterior approach to both groins was pioneered by Cheatle and Henry [9]. McEvedy introduced the unilateral procedure in 1950 [9]. Stoppa [10] employed the bilateral access for prosthetic repair and, in his early experience, had a high rate of recurrence. Similarly, Wantz, with this operation, reported a figure of 11.6% in his first 40 patients [11]. Subsequently, this rate fell to 1.9%. Fernandez-Lobato et al. [12] believed the Stoppa technique required an initial learning curve of 20–30 cases. Kurzer et al. [13], using Wantz’s unilateral posterior preperitoneal repair for anterior groin recurrences and thereby avoiding scar, had 25% of their operations recur in their first 20 patients. Later, the figure was 1%.

465 Chapter 60 · Who Has the Major Role in Hernia Surgery: The Surgeon or the Material?

Schroder et al. [14] found a recurrence rate of 18.2% in their first 36 patients who received the Kugel patch preperitoneal hernioplasty. The later incidence was 2.9%. The overall results with open posterior preperitoneal prosthetic repair indicate that there is a learning curve during which complications, including recurrence, are more likely. Schroder et al. [14] considered its extent to be 40 cases, and Van Nieuwenhove et al. [15], in a study of 450 Kugel repairs, estimated a training period of 25–35 patients, depending on the surgeon’s experience with the anatomy. Similar learning curves were developed for incisional herniation and hiatal herniae, the latter for open [16] and laparoscopic repair [17]. The principles of open anterior or posterior preperitoneal mesh herniorrhaphy apply to laparoscopic repair. Therefore, experience with the former facilitates performance of the latter, which is technically demanding and therefore requires an extended learning curve if initial recurrences are to be avoided. Wright and O’Dwyer [18] suggested that 30–40 supervised cases are needed for the groin. Beets et al. [19] quoted a consensus of 50 repairs, while DeTurris et al. [20] cited 30–50. Neumayer et al. [21], comparing the results of open mesh and laparoscopic repair of inguinal hernia in male veterans, found that general surgeons who were supervised for their initial 25 laparoscopic hernioplasties had a later recurrence rate that plateaued only after 250. It appeared that an inexperienced surgeon employing this new and demanding technique requires more training. However, in a later report [22], these authors raised the question of whether, despite experience, aging affects a surgeon’s performance, especially using newer, more challenging techniques, such as laparoscopy and robotics.

Conclusions In summary, pioneers in herniology have, over the last two centuries, asserted that a surgeon’s skills and experience are more important than the material used to cure abdominal herniation. These sentiments encouraged the development of herniology as a subspecialty of general surgery. The Shouldice clinic [4] introduced learning curves for new staff so

60

that they could avoid initial complications, including recurrence. Kingsnorth [5] did likewise for registrars. Later, the new gold standard for groin repair, the Lichtenstein operation, was exempted because its rate of recurrence was significantly less than that of the supplanted Shouldice procedure. Preperitoneal prosthetic repair required more training (20–30 cases). A similar learning curve was recommended for the repair of incisional and hiatal herniation, open or laparoscopic. Laparoscopic repair of inguinal herniae required a more extended learning curve (30–50 cases). However, in 2004 a multicenter Veterans Administration study [21] indicated that for general surgeons, even this figure was inadequate. A later follow-up in 2005 [22] raised the question of whether aging countered the value of surgical experience when sophisticated technology, i.e., laparoscopy, is employed. These data support the axioms of pioneering herniologists.

References 1. Cooper AP (1804) The anatomy and surgical treatment of inguinal and congenital hernia [preface]. Cox, London 2. Wantz GE (1989) The Canadian repair: personal observations. World J Surg 13:516–521 3. Gilbert AI, Graham MF, Young J, et al. (2006) Closer to ideal solution for inguinal hernia repair: comparison between general surgeons and hernia specialists. Hernia 10(20:162–168 4. Glassow F (1970) Recurrent inguinal and femoral hernia. BMJ (1):215–216 5. Kingsnorth AN, Britton BJ, Morris PJ (1981) Recurrent inguinal hernia after local anesthetic repair. Br J Surg 68:273–275 6. Kingsnorth AN, Gray MR, Nott DM (1992) Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia. Br J Surg 79(10):1068– 1070 7. Harvey MH, Johnstone MJS, Fossard DP (1985) Inguinal herniotomy in children: a five year survey. Br J Surg 72:485–487 8. Read RC (2004) Milestones in the history of hernia surgery: prosthetic repair. Hernia 8(1):8–14 9. Read RC (2001) Use of the preperitoneal space in inguinofemoral herniorrhaphy: historical considerations. In: Bendavid R (ed) Abdominal wall hernias: principles and management. Springer, New York, pp 11–15 10. Stoppa RE, Warleumont CR (1989) The preperitoneal approach and prosthetic repair of groin hernia. In: Nyhus LM, Condon RE (eds) Hernia, 3rd edn. Lippincott, Philadelphia, pp 199–216

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Chapter 60 · Who Has the Major Role in Hernia Surgery: The Surgeon or the Material?

11. Wantz GE (1989) Giant prosthetic reinforcement of the visceral sac. Surg Gynecol Obstet 169:408–417 12. Fernandez-Lobato R, Tartas-Ruiz A, Jimenez-Miramon FJ (2006) Stoppa procedure in bilateral inguinal hernia. Hernia 10(2):179–183 13. Kurzer M, Belsham PA, Kark AE (2002) Prospective study of open preperitoneal mesh repair for recurrent inguinal hernia. Br J Surg 89:90–93 14. Schroder DM, Lloyd LR, Boccaccio JE, et al. (2004) Inguinal hernia recurrence following preperitoneal Kugel patch repair. Amer Surg 70:132–136 15. Van Nieuwenhove Y, Vansteenkiste F, Vierendeels T, et al. (2007). Open preperitoneal hernia repair with the Kugel patch: a prospective multicenter study of 450 repairs. Hernia 11(1):9–13 16. Orringer MB, Skinner DB, Belsey RH (1972) Long term results of the Mark IV operation for hiatal hernia and analyses of recurrences and their treatment. J Thorac Cardiovasc Surg 63:25–33 17. Puri V, Kakarlapudi GV, Awad ZT, Filipi CJ (2004) Hiatal hernia recurrence: 2004. Hernia 8(4):311–317 18. Wright D, O’Dwyer RJ (1998) The learning curve for laparoscopic hernia repair. Semin Laparoscop Surg 5(4):227– 232 19. Beets GL, Dirksen CD, Go PMNYH, et al. (1999) Open or laparoscopic preperitoneal mesh repair for recurrent inguinal hernia? Surg Endoscop 13:323–327 20. DeTurris SV, Cacchione RN, Mungara A, et al. (2002) Laparoscopic herniorrhaphy: beyond the learning curve. J Am Coll Surg 194 (15):65–73 21. Neumayer L, Giobbie-Hurder A, Jonasson O, et al. (2004) Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 350(18):1819–1827 22. Neumayer LA, Gawande AA, Wang I, et al. (2005) Proficiency of surgeons in inguinal hernia repair: effect of experience and age. Ann Surg 243 (3):344–352

60

VII

VII Pro and Contra

62

In Support of a Standard Technique for Inguinal Hernia Repair – 475

63

In Support of Individual Selection of Technique as Related to the Patient–Improvement by Better Selection of Patients Who Can Be Offered a Less Risky Technique: Groin Hernia – 479

64

In Support of Standard Procedure in Abdominal Hernia Repair – 485

65

In Support of Individualized Procedures in Abdominal Wall Hernia Repair – 493

66

In Support of Standard Procedure in Hiatal Hernia Repair – 503

67

Strategy To Improve the Results? In Support of Individualized Procedures in Hiatal Hernia Repair – 513

68

Questionnaire

– 521

61

Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery with Procedures Adjusted to Individual Patients U. Klinge and A. Fiebeler

468

Chapter 61 · Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery

Introduction

61 Surgeons have been working for decades to improve their technique and to develop better procedures. In doing so, they try to prove the effect of every modification by clinical randomized controlled trials (RCTs). The process should result in a best technique that can then be considered the gold standard. This recommendation is outlined in so-called guidelines offering evidence-based knowledge to every physician. However, although RCTs have been performed with increasing efforts, these often fail to confirm any significant differences between the groups involved. Furthermore, after replication by other investigators, the overall results differ considerably in outcome, making interpretation of the results rather complicated. Even the collection of several trials in meta-analyses often does not ease interpretation. It appears that for some questions, the RCT instrument needs some support to verify the superiority of one procedure over another. What might be the reason that even marked expansion of cohort size frequently does not show clearer results? For explanation, it may be helpful to look at our general concepts of disease in more detail.

Different Concepts of Disease A disease is assumed to be best treated in a standardized way, and its impact on the outcome can be tested by an RCT. An RCT is based on the assumption that the disease process is uniform in every patient. Individual patients are considered as average patients since their individual differences will be compensated for by randomization. This first concept of assuming one disease treated by one standard therapy is the domain of the RCT and usually does not offer serious problems. This is true for many experimental settings with a limited and known number of influencing effects. However, for others the number of factors relevant to the prognosis seems to be uncountable. Besides technical aspects, an increasing number of biological reasons seem to interfere with the results, e.g., gene polymorphism or functional imbalances in the proteosome. Unfortunately, we do not know which of the 40,000 genes (or all?) and the even

more numerous proteins have to be considered. Furthermore, if a relevant impact of these biological conditions is suspected, it is obviously impossible to control all of these components in detail. Consecutively, on the molecular level it has to be accepted that every patient will react and respond a little bit differently than another. Thus, this second concept assumes relevant differences between every individual and consequently results in an individual disease that requires individualization of therapies. The second concept may best reflect the true diversification of diseases; however, it is unsuitable for developing practical approaches to treat our patients. The resulting picture of thousands of individual diseases and treatments is too complex to derive principles and guidelines that can be taught to our students and residents. A compromise between the two extremes can be a third concept that considers several subgroups of patients with prognostic differences in disease progress, each demanding specific stage-related therapies. This concept is already well established for cancer therapy; cancer surgery is adapted to the tumor stage to provide comparable subgroups, which can then be tested by RCTs. Instead of the first concept being applied, tumor patients are considered to be nonhomogeneous and are grouped according to certain influencing constellations concerning their prognosis for survival. According to defined risk factors, different therapies are tailored to each individual patient, forming a decision tree for selecting the individualized best therapy. In the following, we discuss whether the optimal therapy for hernia can be derived from applying the first concept or whether better results can be achieved by using the latter concept, which is also referred to as a »tailored approach.« Furthermore, general remarks are given on how to identify therapies with a clear causal impact on the result as predicted by the first concept and how to test the quality of a tailored approach.

A Century of Seeking the Best Standard Procedure To Repair a Hernia? The surgical repair of groin hernia started with Bassini in 1884 as a suture repair, was modified

469 Chapter 61 · Two Controversial Concepts: Standard Procedure in a Standard Patient

by Shouldice in 1944, and changed toward mesh repair with the introduction of the Lichtenstein repair in 1986 and the laparoscopic procedures at the beginning of the 1990s. Since Bassini, the recurrence rate for suture repair had been <5% in selected patients, but the long-term recurrence rate was widely constant around 10–15%. Treatment of recurrent hernia had been more difficult, with recurrence rates of up to 30–50%. Reinforcement of tissue with meshes improved the results, with recurrence rates of <1% in selected patients [1], a long-term rate of 5–10%, and a rerecurrence rate of 10–20% [2]. Several meta-analyses concluded that meshes reduce the recurrence rate by half, regardless of whether they are implanted in open surgery or laparoscopically [3]. In the guidelines of many countries (including the United Kingdom and the Netherlands), Lichtenstein mesh repair is claimed to be the standard operation for primary hernia in the adult patient [1]. Incisional hernia of the abdominal wall is even more difficult to treat. Despite countless attempts to improve the standard technique for closing a laparotomy, the long-term incidence for developing an incisional hernia is up to 20%, and for parastomal hernia it is even higher, up to 50%. The rerecurrence rate after suture repair is >50%. Again, reinforcement with meshes markedly reduces the recurrence rate to <10% [4]. To date, there is no evidence regarding whether the onlay position is as good as the sublay position in all cases, but mesh repair is regarded as the standard for repair of incisional hernia. After more than 100 years of improving our technical skills, we can state that reinforcement of tissues by meshes hinders recurrence. However, despite many attempts to identify the best closure technique, we still do not know how to close a laparotomy sufficiently. And up to now, no RCT has proven any beneficial effect of a new technique. What might the technical challenge be when approximating just two layers of the abdominal wall? Until now, despite the clear and evident superiority of mesh techniques proven by many RCTs (and even several meta-analyses), we are still operating on 10–15% of our patients with a groin hernia because of a recurrent hernia–for decades without any sign of reduction even though we are

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using meshes in the huge majority of our patients. What might be the reason that we could not solve this simple technical problem, and why did many RCTs fail to lead to significant improvement of our techniques?

Recurrence as a Technical Failure? From an engineer’s technical point of view, abdominal wall hernia repair needs any adequate procedure to simply close the hernia gap. A perfect technique and procedure should be decisive for the result and should permanently prevent recurrence. However, in some cases a technical failure may occur and will result in recurrence. For a group of comparable cases, this should manifest after a mean delay of some months or years (± standard deviation). If a procedure is used that works better, there may be either fewer recurrences or the recurrence should appear later (⊡ Fig. 61.1). As a consequence, the outcome curve will show an S-shaped configuration with its transflexion point at the time of peak incidence. This is well known for engineers and is in accordance with car breakdowns due to certain technical defects [5]. Correspondingly, if we assume that every patient with any kind of hernia is treated with a standard procedure, in the case of a standard patient with a standard hernia we should expect that recurrences develop after a standard delay ± standard deviation.

Recurrence

Time ⊡ Fig. 61.1. Incidence of a technical failure (recurrence; red solid line) and its cumulative incidence curve (blue dotted line)

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Chapter 61 · Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery

Do we have data to support such courses of hernia recurrences? No, clearly this is not the rule. Studying incisional hernia in a long-term survey, Luijendijk et al. found unexpectedly high rerecurrence rates even after mesh repair: >60% after suture and >30% after mesh repair [6, 7]. Many of these recurrences developed after a long delay from the previous operation, and even more intriguing, the courses showed cumulative incidences that formed curves with a roughly linear shape. Similar courses are seen in the cumulative rate of operations for recurrence depicted from epidemiological databases. In contrast to the expected peak incidence with an S-shaped outcome curve, for groin hernia [1] as well as for incisional hernia [8], the cumulative incidence rises constantly over time, not showing any S-shaped inflexion or reaching a plateau at the end. Is this really worth thinking about? And does it help addressing the problem of standard versus tailored treatment? Regarding the linear rise of a cumulative recurrence rate, the best explanation is still that there is not one specific reason but that there are many of them. Conclusively, the development of a recurrence cannot be related to one (i.e., technical) problem that can be overcome by one technical solution. In other words, it is unlikely for one standard procedure to address all of these problems and to improve all results significantly. Consequently, if we do not see a standard failure with a standard delay resulting in an S-shaped outcome curve, it must be suspected that the basic assumption of a standard patient with a standard hernia is not advantageous. Recent investigations of wound healing confirm the evidence that recurrence in hernia patients is a problem of a defective biological network rather than a technical failure. Because the defective scarring process is triggered by a complex network of biological interferences, it is not surprising that the causally relevant reason may differ with each patient. The superimposition of all the many different possible reasons with their different incidence peaks will result in a linear rise of the outcome curve, as in fact is seen in patients after hernia repair (⊡ Fig. 61.2). Not the least consequence of this model is that it questions the role of RCTs. These require either (sub)groups

Time course of failure with linear rise due to accumulation of many incidences 1 Incidence of damage cumulative »survival«

0

Time

⊡ Fig. 61.2. Incidences of several possible failures (red solid line) and their superimposition toward a linear rise in the cumulative incidence curve (blue dotted line)

comparable in their failure risk or a mechanism to be tested that has an undoubted causal relevance for the occurrence of a failure. Neither may be assumed in the case of linear outcome curves. In the case of linear cumulative incidences, an alternative therapy may show a reduced rate of complications at any time point; however, without having reached a plateau, it is only a delayed manifestation of the problem. Furthermore, if the results are not corrected for age-related morbidity, every delay per se will suggest a reduced number of complications. In summary, the configuration of epidemiological outcome curves indicates that recurrences should not be regarded as simple technical failures but rather as a complex problem of biology, and that we should not look for a standard failure in a standard patient.

Technical Solution for a Complex Biological Problem Currently, the technical solution to the biological problem means reinforcement of tissue with meshes. One way to overcome poor-quality scarring in patients is to supply an extended subduction of the mesh underneath healthy scar-free tissue. The important question for the surgeon is whether the overlap that can be achieved by a stan-

471 Chapter 61 · Two Controversial Concepts: Standard Procedure in a Standard Patient

dard technique is independent of the patient’s individual type of hernia or whether it is necessary to tailor various techniques to the individual patient. We present some considerations that all indicate that the procedure must at least be selected in view of hernia size and location. A larger hernia gap needs a larger mesh. However, in the case of a large mesh, even small shrinkage of <15% may reduce the absolute width of the mesh by >4 cm and thereby cut the overlap in half! Next, surgeons should consider that positioning the mesh on fat tissue is more likely to result in slippage of the mesh and shortening of the overlap; thus, larger meshes will be advantageous in such cases. This is in accordance with the clinical results of increased recurrence rates in adipose patients when the mesh had been placed in the preperitoneal fat [9]. Furthermore, there are some areas of concern where anatomy makes it difficult to supply a sufficient overlap, such as close to bony structures (e.g., the iliac crest or costal arch). In these locations, intraperitoneal onlay mesh techniques may provide greater overlap than meshes in the onlay position. Because the various techniques differ considerably in the mesh size used and the overlap that is achievable by dissection, we must tailor the procedure to the patient. This means we have to select the technique that fits best and that provides the biggest overlap with the lowest risk for the patient.

Principle and Quality Control of Tailored Surgery The concept of tailored surgery does not mean treating patients according to some vague expert’s opinion. Quality control is required, just as for every other therapeutic concept, although the evaluation of a decision tree requires studies other than the RCT. The final goal of any tailored approach is to achieve the best result in all patients, while using various techniques in nonhomogeneous groups of patients. First of all, we have to define criteria for such a decision tree regarding which patient should receive which technique. Checking the results after x time and analyzing the complications in relation

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to the procedure must show whether any problems were caused by poor technique in the right patient or by good technique in the wrong patient. If technical failure is suspected, surgical skills need to be improved. If a technical failure can be excluded and the problem was simply the wrong technique for the patient concerned, the decision tree needs to be modified such that the next similar patient will receive a more appropriate technique. After some time, all results have to be checked again. Furthermore, all results need to be compared with other clinics and other decision trees. Finally, it is likely that decision trees with the best results will be rather similar; however, it will be possible to achieve good results with several different decision trees in different target groups of patients. Not the least advantage is that for this tailored approach, no patient has to be randomized; therefore, every surgeon and every clinic can take part in a comprehensive comparison of patients’ outcomes. Even in theory, a tailored approach will lead to superior results if corresponding subgroups can be identified. Whereas for an entire cohort two therapies may have a similar complication rate, this may be eliminated if the procedure is tailored to subgroups with less risk for a specific therapy (⊡ Fig. 61.3). The previous remarks focus on recurrence; however, the principal aspects of a tailored approach should be applied for many other treatment regimens, such as for curing infection, pain, etc. Further, it is necessary to weight the importance and relevance of the complications, advantages, and disadvantages to the patient and the surgeon as well as to the institution.

Conclusion Although we may not feel comfortable with it, we have to accept that there is no easy scientific answer [10] that offers the one golden solution. Only in the case of S-shaped outcome curves we are allowed to assume that we are treating standard patients with standard procedures, and in this case we are right to expect standard results. In the case of linear outcome curves, we should consider whether a tailored approach is more appropriate.

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Chapter 61 · Two Controversial Concepts: Standard Procedure in a Standard Patient Versus Tailored Surgery

Assumption szenario III: „tailored approach“ Technique 1: laparoscopical

5%

A

Technique 2: open

B

A

B

Technique 2 (open) for patients of group A (suprasymh., subxiphoid.)

A

B

5%

A

B

Technique 1 (laparoscopical) for patients of group B (lateral, close to bones)

⊡ Fig. 61.3. Two different techniques, each with 5% complications. For technique 1 it manifests in subgroup A, whereas for technique 2 it occurs in subgroup B. A tailored approach with treatment of A with technique 2 and of B with technique 1 will even be able to eliminate all complications

However, once we have identified subgroups of patients with identical risk profiles for a complication, S-shaped outcome curves should be available for these patients, and those subgroups then should be compared with RCTs. If not, we should try to improve the quality of our decision tree for the tailored approach. Nevertheless, there is no doubt: Every procedure has to be performed carefully and correctly according to the well-established standards–which means, tailor your standards!

References 1. Schumpelick V, Fitzgibbons R (2007) Recurrent hernia– prevention and treatment. Springer, Berlin 2. Eklund A, Rudberg C, Leijonmarck CE, et al. (2007) Recurrent inguinal hernia: randomized multicenter trial comparing laparoscopic and Lichtenstein repair. Surg Endosc 21:634–40 3. McCormack K, Scott NW, Go PM, Ross S, Grant AM (2003) Laparoscopic techniques versus open techniques for inguinal hernia repair. Cochrane Database Syst Rev 2003 (1):CD001785 4. Klinge U, Krones CJ (2005) Can we be sure that the meshes do improve the recurrence rates? Hernia 9:1–2 5. Klinge U, Binnebösel M, Rosch R, Mertens P (2006) Hernia recurrence as a problem of biology and collagen. J Minim Access Surg 2:151–4

6. Luijendijk RW, Hop WC, van den Tol MP, et al. (2000) A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 343:392–8 7. Burger JW, Luijendijk RW, Hop WC, et al. (2004) Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–83; discussion 583–5 8. Flum DR, Horvath K, Koepsell T (2003) Have outcomes of incisional hernia repair improved with time? A population-based analysis. Ann Surg 237:129–35 9. Rosemar A, Hana N, Ulf A, Staffan H, Pär N (2008) Groin hernia surgery and body mass index: a study based on a national register (S). In: Proceedings of the 30th Congress of EHS GREPA, Sevilla, Spain, 7–10 May 2008 10. Klinge U, Dahl E, Mertens P (2007) Problem poser–how to interpret divergent prognostic evidence of simultaneously measured tumor markers? Comput Math Methods Med 8:71–75

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In Support of a Standard Technique for Inguinal Hernia Repair M. P. Simons

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Introduction

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Is standardisation of treatment of inguinal hernia necessary? Yes, it is necessary because the vast majority of surgeons are not dedicated hernia surgeons, so they need guidance and training. Looking for a »standard« technique that is (relatively) easy to learn, safe, cheap, reliable, and reproducible is important. In this chapter, factors that influence the choice of technique are discussed, and the European Guidelines are used to demonstrate that standardisation is indeed possible and recommended. What is a standard technique? We know that specialists such as Amid use a Lichtenstein technique for almost all repairs. The same can be said of other techniques such as Shouldice, Stoppa, and endoscopic repair techniques. We, sadly, also know that many surgeons do not use the technique as described by the originator. »Choose the surgeon, not the technique« is a known adagium. Is a »standard« technique truly standard in most cases? And do surgeons who state that they use a standard technique deviate from this standard in some (or many) cases? Before we can be pro standard technique, factors influencing the possibility of stating this must be identified. The type of hernia, type of patient, type of surgeon, and the setting in which he or she operates are discussed (⊡ Table 62.1).

⊡ Table 62.1. Factors that influence the possibility of using one standard technique in inguinal hernia repair (ASA American Society of Anesthesiologists) Patient-related  Gender  Obesity  ASA class  Prior groin surgery  Comorbidity  Type of anaesthesia  Preference Type of hernia  Indirect  Direct  Combined  Recurrence (prior technique?)  Femoral hernia Surgeon-related  Specialist in hernia centre  Specialist in general practice  Laparoscopic surgeon  General surgeon (dedicated?) Resident

Comorbidity: As with ASA class, some patients require a low-risk technique under local anaesthesia. Type of anaesthesia: Endoscopic surgery requires general anaesthesia.

Gender: Female patients have a higher rate of chronic pain and a higher risk of femoral hernia.

Preference: Although little data are available on this subject, nobody will contradict the fact that some patients prefer a technique under local anaesthesia whereas other patients request a minimally invasive technique.

Obesity: Morbidly obese patients require an individualised approach.

Type of Hernia

Patient-Related Factors

American Society of Anesthesiologists (ASA) class: In many cases, ASA 3 and 4 patients have contraindications to general anaesthesia, precluding the use of certain techniques. Prior groin surgery: Prior groin surgery, prior lower abdominal surgery, radiation, and other factors greatly influence the choice of technique.

The normal distribution (as measured in large studies and national databases) of inguinal hernias is as follows: Indirect 50–55% Direct 30–35% Combined 10–15% Bilateral 10–15% Recurrent 10–15%

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477 Chapter 62 · In Support of a Standard Technique for Inguinal Hernia Repair

⊡ Table 62.2. Differences in hernia repair among countries Types of inguinal hernia repair Country

Year

Conventional

Open mesh

Endoscopic

Other

Netherlands

2006

4%

78%

19%

Denmark

2006

2.5%

82.5%

15%

Finland

2006

7%

81%

8%

3%

France

2006

14.9%

46%

34%

4.6%

Poland

2006

38%

60%

1%

Austria

2006

76%

24%

Hungary

2007

60%

34%

6%

Sweden

2006

8.5%

82%

9%

The distribution shown precludes the use of one standard technique in inguinal hernia. It is a fact, though, that around 70–75% of inguinal hernia repairs are for unilateral primary cases. For these cases, a standard approach (either by anterior or endoscopic approach) is feasible. But a standard »Lichtenstein surgeon« will have difficulty treating a complex third recurrent hernia after open techniques or bilateral large recurrent hernias. A »laparoscopic surgeon« will have difficulty when a patient specifically requests an operation under local anaesthesia or has a difficult recurrence after prior preperitoneal repair.

Level of the Surgeon Expert surgeons use a standard technique for most cases and agree that surgeons need proficiency in at least two techniques–preferably an anterior technique and a posterior technique–to be able to treat all cases. Laparoscopic surgeons will state that almost all cases can be treated by laparoendoscopic techniques. But there are contraindications to these techniques, including previous lower abdominal surgery, radiation, prior mesh implantations, and inability to undergo general anaesthesia. Guidelines advise teaching residents both approaches (anterior and posterior).

Is Hernia Surgery Standardised? Many techniques are being used, and the literature shows that the differences among countries are significant (⊡ Table 62.2). There is a growing indication that in European and North American countries, a majority of inguinal hernias are treated by a Lichtenstein technique. Endoscopic repair varies from 1% to 24%. Miscellaneous other techniques are used in 5–20% of cases, but one could postulate that these are standard procedures (for example, Prolene Hernia System, Kugel, plug-and-patch), as is the Lichtenstein. In the Netherlands, guidelines in 2002 recommended a Lichtenstein repair (as a standard) for unilateral uncomplicated inguinal hernia, an endoscopic repair for bilateral hernias (if the expertise was available), and a tailored approach for recurrent hernias. An implementation study was performed. In 2001, all inguinal hernia surgeries in 73 hospitals (70% of the total) were analysed after 1 year of follow-up (charts only). A few years after implementation of the guidelines (2006), the study was repeated. Results are shown in ⊡ Table 62.2. It is postulated that the increase in mesh (predominantly Lichtenstein) has decreased the percentage of reoperations for recurrence from 14% to 11%.

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What Do the European Guidelines Recommend?

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Guidelines are developed to improve practice, especially general practice. Those involved in developing the European Guidelines have, after considering the following factors, come to the following recommendations regarding the following: ▬ Risk of recurrence ▬ Safety (risk of complications) ▬ Postoperative recovery and quality of life (resumption of work) ▬ Grade of difficulty and reproducibility (learning curve) ▬ Costs (hospital and societal)

Level A All male adult (>18 years) patients with a symptomatic inguinal hernia should be operated on using a mesh technique. When a nonmesh repair is considered, the Shouldice technique should be used. The open Lichtenstein and endoscopic inguinal hernia techniques are recommended as best evidence-based options for repair of a primary unilateral hernia, providing the surgeon is sufficiently experienced in the specific procedure.

Level D For large scrotal (irreducible) inguinal hernias, after major lower abdominal surgery, and when no general anaesthesia is possible, the Lichtenstein repair is the preferred surgical technique. It is recommended that in the case of a recurrent inguinal hernia following an anterior approach, a preperitoneal mesh should be placed, preferably by means of an endoscopic technique. It is recommended that an anterior approach be used in the case of a recurrent inguinal hernia that was treated with a posterior approach. Because evidence is scarce, a tailored approach is recommended for female patients and young adults.

What Does the Literature Recommend? Most trials describe results between standard procedures, but there is, of course, an inclusion bias

in trials. Specific patient categories are not randomised, usually because they require a tailored approach. O’Dwyer’s MRC trial is an example of a study in which an endoscopic »standard« operation was compared with a »tailored open approach.« In the open group, around 20% of patients were operated on with a nonmesh technique and 80% by a Lichtenstein technique. There was no difference in recurrence after 2 years.

Conclusion After analysing the arguments discussed above, this author concludes that an approach using one standard technique for all inguinal hernias is not feasible. It is possible, though, to use one standard technique for the 70–75% primary unilateral cases. This can be an open mesh technique such as Lichtenstein. Some patients will prefer an endoscopic approach! This can also be a »standard« endoscopic approach. Some patients will have contraindications for this technique, and it cannot be performed under local anaesthesia. Recurrent inguinal hernia requires an individualised approach with at least two and maybe even three techniques, depending on prior technique and patient factors. It is important to determine for which type of surgeon how this situation should be handled. A specialist surgeon will be used to individualising treatment and will master different techniques. On the other hand, in a teaching hospital, surgeons and residents should start by teaching/learning one »standard« technique well for uncomplicated cases. This leaves 20–25% of the cases, such as bilateral hernias, recurrent hernias, female patients, and young patients, for which dedicated or (sub) specialised surgeons should be prepared to choose between an open anterior or a posterior approach (author’s opinion). The posterior approach can be performed endoscopically or via an open approach. In certain cases, a mesh might not be necessary. Evidence is unclear whether females and young adults with an indirect primary hernia require mesh.

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In Support of Individual Selection of Technique as Related to the Patient–Improvement by Better Selection of Patients Who Can Be Offered a Less Risky Technique: Groin Hernia B. D. Matthews

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Introduction

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Dr. David Sackett of McMaster University in Ontario, Canada, defined evidence-based medicine as the judicious use of the best current evidence in making decisions about the care of the individual patient. He further remarked that evidence-based medicine is a means to integrate clinical expertise with the best available research evidence and patient values. Clinical outcome research in surgery is commonly criticized for a lack of prospective randomized trials to compare alternative surgical techniques or operative versus nonoperative treatment when the option of avoiding surgical intervention is considered appropriate. Despite these shortcomings, there is perhaps no area in surgery in which more level I evidence is available to guide clinical practice and surgical decision making than in the care of patients with inguinal hernias. Because the cumulative incidence of inguinal hernias in males is approximately 14% at a median follow-up of 18.2 years, as reported in a recent publication from the first National Health and Nutrition Examination Survey, the application of clinical outcome studies to inguinal hernia patients is critical to guide surgeons toward appropriate care of this common surgical problem [1]. Minimizing recurrent hernias, chronic inguinodynia, and additional postoperative morbidities and decreasing postoperative recovery to facilitate a return to self-reliance are paramount. Despite an enormous quantity of clinical outcome data comparing open tension-free to primary tissue repair techniques and open tension-free to laparoscopic inguinal hernia repair, controversy persists regarding the use of a standard versus a tailored approach to the management of groin hernias. Patient care guidelines for inguinal hernia repair were published by the Society for Surgery of the Alimentary Tract in 2006 and the National Institute for Clinical Excellence for the NHS (United Kingdom) in 2004, but they are vague in regard to the use of laparoscopic inguinal hernia except for the need for appropriate training and experience in a minimally invasive approach. Many techniques exist, including primary tissue repair, open tension-free anterior or retroperi-

toneal repair, and laparoscopic transabdominal (TAPP) or total extraperitoneal (TEP) inguinal hernia repair. Watchful waiting for asymptomatic or minimally symptomatic inguinal hernias is also considered standard of care. Primary tissue repair is infrequently performed, but it is often done for incarcerated and/or strangulated inguinal hernias when wound contamination is a concern. A Cochrane Database review in 2001 reported a 50% reduction in inguinal hernia recurrence when a tension-free repair was performed, providing additional evidence of the shortcomings of primary repair [2]. Nevertheless, familiarity and experience in primary tissue repair is important when a surgeon is faced with an incarcerated and/ or strangulated hernia or unique circumstances when a mesh-based repair is deemed inappropriate. A tailored approach to the individual patient using evidence-based medicine will allow for the integration of surgical expertise and approach with unique patient characteristics. This chapter discusses important patient and surgeon variables to consider in order to optimize patient outcomes through selection of an appropriate technique for patients undergoing elective inguinal hernia repair.

Watchful Waiting Versus Inguinal Hernia Repair Upon initial evaluation of a patient with an inguinal hernia, the surgeon must decide whether inguinal hernia repair is required. A doctrine that the presence of an inguinal hernia, even if asymptomatic, is an indication for repair to prevent an acute hernia emergency from incarceration and/ or strangulation has been challenged by two recent prospective randomized trials. O’Dwyer et al. reported only one (1.3%) patient out of 78 who developed an acute incarceration at a median follow-up of 574 days [3]. The rate of crossover to inguinal hernia repair was 26% at 15 months. Two patients in the observation group who subsequently underwent surgery suffered a myocardial infarction and cerebrovascular accident, respectively. The authors concluded that observation may only delay surgical intervention. Neverthe-

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less, watchful waiting would be appropriate for high-risk patients since an acute hernia accident is quite rare. In a comparable study, Fitzgibbons et al. reported the frequency of acute incarceration to be 1.8 per 1,000 patient-years inclusive of patients followed for as long as 4.5 years [4]. The probability of crossover from watchful waiting to inguinal hernia repair was approximately 23% at 3 years of follow-up. Delaying repair of an asymptomatic or minimally symptomatic inguinal hernia did not have adverse effects on subsequent operative intervention or postoperative outcomes [5]. Why would watchful waiting decrease patient morbidity? A population-based questionnaire in the Netherlands of consecutive patients who underwent inguinal hernia repair over 68 months reported that 40.2% of patients had »some degree of pain,« with 21% being confronted with some degree of limitation in daily functioning and 1.9% experiencing severe pain [6]. Therefore, due to a high incidence of chronic pain, watchful waiting is particularly relevant for patients with asymptomatic or minimally symptomatic hernias.

Laparoscopic Versus Open Inguinal Hernia Repair Over 40 prospective randomized single-institution or multi-institutional studies comparing laparoscopic (TAPP and TEP) inguinal hernia repair to open tension-free inguinal hernia repair have been reported worldwide. A recent review by Takata and Duh summarizing these publications demonstrated that laparoscopic inguinal hernia repair has a beneficial role in decreasing chronic inguinodynia and recurrence rates and is associated with shorter convalescence and a faster return to work and activities in patients with recurrent, bilateral, and primary inguinal hernias [7]. In a prospective randomized trial of laparoscopic inguinal hernia repair and anterior tension-free repair for recurrent inguinal hernias, patients experienced less postoperative pain and fewer days of sick leave after a laparoscopic approach. Cumulative 5-year recurrence rates were equivalent [8]. Indeed, laparoscopic inguinal hernia repair is most often performed for bilateral and recurrent hernias. As

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a consequence, laparoscopic techniques account for only 20–30% of inguinal hernia repairs in the United States. Reasons to not perform laparoscopic inguinal hernia repair for a unilateral primary hernia include surgeon preference, lack of expertise in minimally invasive techniques, complexity of the hernia (e.g., inguinoscrotal, incarcerate), and cost. Laparoscopic inguinal hernia repair is almost always performed under general anesthesia, certainly limiting its use. Ideally, all patients would receive the treatment that provides the most durable repair with the least amount of perioperative morbidity (pain, quality-of-life limitations, and cardiac, pulmonary, and non-herniarelated complications). Although a few risks associated with hernia recurrence and even chronic pain have been established, patient-specific and hernia-specific factors associated with postoperative complications and hernia recurrences are being defined. There is a possibility that minimally invasive techniques are underutilized or, alternatively, not performed in the appropriate patient. Even though the majority of inguinal hernia repairs are day cases, risk stratification of perioperative morbidity in addition to recurrence and chronic pain after laparoscopic and open inguinal hernia repair would be useful in determining an appropriate surgical approach. The Patient Safety in Surgery (PSS) Study, a collaboration between the U.S. Department of Veterans Affairs (VA) National Surgical Quality Improvement Program and the American College of Surgeons and funded by the Agency for Healthcare Research and Quality, took 97 different perioperative variables (patient demographics, preoperative risk factors, preoperative laboratory values, operative values, and postoperative outcomes) and cross-referenced them to the top 10 most frequent current procedural terminology (CPT) codes [9]. In the VA system, open inguinal hernia repair (the 1st most common code), recurrent inguinal hernia repair (6th), and laparoscopic inguinal hernia repair (8th) are represented. The PSS Study has evolved to include private sector hospitals, with open inguinal hernia repair being the 2nd most common CPT code. Because the aim of the PSS Study is to minimize postoperative morbidity and mortality and to risk-adjust adverse events for

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common procedures in order to compare different hospital systems, information on inguinal hernia repair will allow surgeons to appropriately riskstratify patients for open and laparoscopic inguinal hernia repair. Matthews et al. have identified risk factors associated with complications and recurrences in patients undergoing laparoscopic and open inguinal hernia repair and have developed a riskassessment model for hernia recurrence using the data from the VA Cooperative Studies Program trial that compared open and laparoscopic surgical techniques for tension-free inguinal hernia repair [10]. Independent patient-specific and surgery-specific variables that predict postoperative complications and recurrence have been defined. Many predictors of complications (e.g., recurrent hernia, inguinoscrotal hernia) were similar between open and laparoscopic inguinal hernia repair, although several variables (e.g., prostatism, surgeon experience) differed based on the surgical approach. Risk for recurrence after an open inguinal hernia repair included a recurrent hernia, preoperative activity level of the patient, American Society of Anesthesiologists class, and whether the hernia had enlarged recently. Using regression analyses, Matthews et al. have also developed predictive models for perioperative outcomes. These models can be used to determine an appropriate surgical approach for an individual patient to reduce the risk of recurrence and complications. Additional studies have reported a predictive risk score for infection after inguinal hernia repair as well as patient characteristics associated with an increased risk of postoperative hematoma following herniorrhaphy. Pessaux et al. developed a global infection score (GIS) dependent on risk factors for infection (age, obesity, and use of a urinary catheter) as determined by multivariate analysis from a database of 1,254 patients [11]. The use of prophylactic antibiotics in patients with a high GIS and/or a laparoscopic inguinal hernia repair appears to be a better option in these patients. Smoot et al. reported that preoperative Coumadin usage was a significant risk factor for postoperative hematoma [12]. Intuitively, a laparoscopic inguinal hernia repair with the potential for bleed-

ing into the widely developed preperitoneal space, or even intraabdominal bleeding, seems a poor choice compared with an anterior tension-free repair in which postoperative bleeding could be managed with less morbidity. As additional studies are reported and risk stratification becomes more reliable, surgeons will need to alter their operative approach to inguinal hernia repair to ensure that they reduce the risks of postoperative morbidity and recurrence. One factor that has not been evaluated is laparoscopic inguinal hernia repair for a recurrent hernia in a patient who has undergone an anterior tension-free preperitoneal inguinal hernia repair. A strategy to repair a recurrent hernia by an opposite approach from the index operation is obscured when the preperitoneal space has been disturbed and used for mesh placement, albeit by an anterior approach. Although laparoscopic transabdominal and extraperitoneal inguinal hernia repair can successfully be performed after previous abdominal and/or pelvic surgery, additional investigation of laparoscopic inguinal hernia repair after the anterior placement of preperitoneal mesh needs to be done. In addition, differentiation of whether laparoscopic transabdominal and extraperitoneal inguinal hernia repair reduce hernia recurrences, chronic pain, or perioperative morbidity has not been elucidated through clinical trials. Evidence is accumulating that experience is important in determining outcomes with regard to hernia recurrence, not only for laparoscopic inguinal hernia repair but also for open inguinal hernia repair [13, 14]. Anterior tension-free preperitoneal inguinal hernia repairs such as the Prolene Hernia System (Ethicon, Somerville, NJ, USA) and Kugel (Davol, Cranston, RI, USA) repair require specific training and an awareness of preperitoneal anatomy and the nuances of mesh placement. Arbitrary case volumes have been projected to define the learning curve, but they do little to define appropriate training. Surgeons need to honestly assess their clinical outcomes and level of technical expertise with any type of inguinal hernia repair and properly choose an approach that places the patient at the least risk for perioperative technique-related complications, recurrence, or chronic pain.

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Conclusions A tailored approach to the individual patient with an inguinal hernia integrates surgical expertise and evidence-based medicine to optimize patient outcomes through the selection of an appropriate technique. As predictors of complications after open and laparoscopic inguinal hernia repair are more clearly defined through large multi-institutional prospective registries, the frequency of chronic pain and the incidence of recurrent inguinal hernias can be reduced, and the relationships between outcomes and patient comorbidities, hernia characteristics, and surgeon experience will be revealed.

References 1. Ruhl CE, Everhart JE (2007) Risk factors for inguinal hernia among adults in the US population. Am J Epid 165:1154– 1161 2. Scott N, Go PM, Graham P, et al. (2001) Open mesh versus non-mesh for groin hernia repair [review]. Cochrane Database Syst Rev (3):CD002197 3. O’Dwyer PJ, Norrie J, Alani A, et al. (2006) Observation or operation for patients with an asymptomatic inguinal hernia: a randomized clinical trial. Ann Surg 244:167–173 4. Fitzgibbons RJ, Giobbie-Hurder A, Gibbs, JO et al. (2006) Watchful waiting vs repair of inguinal hernia in minimally symptomatic men: a randomized clinical trial. JAMA 295:285–292. 5. Thompson JS, Gibbs JO, Reda DJ, et al. (2008) Does delaying repair of an asymptomatic hernia have a penalty? Am J Surg 195:89–93 6. Loos MJA, Roumen RMH, Scheltinga MRM, et al. (2007) Chronic sequelae of common elective groin hernia repair. Hernia 11:169–173 7. Takata MC, Duh QY (2008) Laparoscopic inguinal hernia repair. Surg Clin North Am 88:157–178 8. Eklund A, Rudberg C, Leijonmarck CE, et al. (2007) Recurrent inguinal hernia: randomized multicenter trial comparing laparoscopic and Lichtenstein repair. Surg Endosc 21:634–640 9. Khuri SF, Henderson WG, Daley J (2007) The Patient Safety in Surgery Study: background, study design, and patient populations. J Am Coll Surg 204:1089–1102 10. Matthews RD, Anthony T, Kim LT, et al. (2007) Factors associated with postoperative complications and hernia recurrence for patients undergoing inguinal hernia repair: a report from the VA Cooperative Hernia Study Group. Am J Surg 194:611–617 11. Pessaux P, Lermite E, Blezel E, et al. (2006) Predictive risk score for infection after inguinal hernia repair. Am J Surg 192:165–171

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12. Smoot RL, Oderich GS, Taner CB, et al. (2008) Postoperative hematoma following inguinal herniorrhaphy: patient characteristics leading to increased risk. Hernia 12:261– 265 13. Neumayer L, Giobbie-Hurder A, Jonasson O, et al. (2004) Open mesh versus laparoscopic mesh repair of inguinal hernia. N Engl J Med 350:1819–27 14. Wilkiemeyer M, Pappas TN, Giobbie-Hurder A, et al. (2005) Does resident post graduate year influence the outcomes of inguinal hernia repair? Ann Surg 241:879–84

Discussion Kurzer: Perhaps we should get away from saying

that recurrence is the only thing we are interested in; some of us have alluded to that. I get patients who come to me and ask if it will last forever, but they don’t really expect the lack of recurrence to last forever. You can’t just operate to get rid of recurrence at all costs, and maybe we have to take into consideration operations that are more likely to cause pain in certain patients. In English, they say that to the man who has a hammer, every problem is a nail. Clearly, if you are a hernia surgeon, you can’t have just one hammer, and you have to have other tools to deal with other hernias. There are clearly different hernias, different problems, different patients. Schumpelick: Could it be that the hernia centers tend more in the direction of standard procedures and that the general surgeons who do [operate on] some hernias take a tailored approach? Kurzer: No, I do not think so… probably more the other way round. I think the general surgeons are the ones who would go through life with just one operation that they use for everyone. It’s perhaps not a bad thing, if the general surgeon has only one procedure that he can do, as long as he recognizes when he sees a patient who has something he can’t deal with and as long as he is happy to send it to someone who can. If he sees someone with a bilateral recurrence and he can only do a Lichtenstein, he sends that patient away to someone who can do a TEP; he doesn’t try to do it himself. I think that is important. Schumpelick: Is it likely that someone who is not used to doing a TAPP or TEP will send the patient away? I have seldom heard about that.

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Deysine: I have a double experience. I worked at the Bellevue Hospital in New York, in a population of malnourished alcoholics, and then I went to work at the VA Hospital in Northport with a lot of different people with different kinds of malnutrition. And then I went to work in my neighborhood, where the income is extremely high, and people usually eat very well and they exercise. These are three different types of human beings; they all are going to heaven but in different conditions. So if you try to standardize and you use for everybody the same procedure, you are going to find different results. Surgeons who came from New York Hospital, a very rich environment, and operated in Bellevue using the techniques they used at the New York Hospital were a disaster. You have to have in your pocket two or three techniques you can use, and [you have to] analyze very carefully the biology of the patient you are going to deal with. Chowbey: I think it is very important to understand that the technique depends on the expertise of the surgeon, a group of surgeons of a department, who have developed an expertise in a particular technique of hernia repair. For example, in our department, we do mainly TEP in the majority of our patients. But at the same time, the group should have a sense of responsibility where they do not stretch their imagination too far, do not stretch their technique too far so as to harm the patient. So if there is a patient after a radical prostatectomy and you find that TEP is going to be difficult, it is a good idea to do an anterior approach. Schumpelick: How important is the wish of the patient when they come to you and say that they want this technique? Today our patients are quite well informed by newspaper and the Internet. Chowbey: This will not happen in our situation. When a patient comes to us, he only comes to us for endoscopic technique because we are known for his technique. So even when a patient comes with a huge, obstructed hernia with half of the omentum in the scrotum, it is our responsibility to modify our technique. For example, in this particular situation, we would still do an extraperitoneal approach. We know it is irreducible; either we do a TAPP and reduce the hernia and then go extraperitoneally—because that is our idea

of strength—or divide the omentum with Ultracision or some device, make a small incision in the scrotum, and mobilize and remove the hernia content. So this is a combination of imagination and expertise. The ultimate bottom line is that the patient should not be harmed. Give the best for your patient; do whatever is best for him. Fitzgibbons: I think that is a very reasonable approach, individualizing to some extent, but, as you said, not too far. Chowbey: In a strangulated inguinal hernia, we go transabdominal with a pneumoperitoneum, reduce the bowel, and look at the viability of the bowel. In a few situations where we were not sure about the viability of the bowel, we did not mind leaving a small 5-mm trocar and putting in an optic and looking at the viability of the bowel after a few hours under local or short sedation. If the bowel is not viable, just open the patient and do a resection. This way, you can extend your expertise to different degrees.

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In Support of Standard Procedure in Abdominal Hernia Repair J. B. Flament

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Introduction

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The incidence of incisional hernia (usually defined as a chronic postoperative defect of the abdominal wall through which intraabdominal viscera protrude beneath the skin). has been reported to be as high as 11–13% of all laparotomies [1, 2]. Surgical repair is difficult in cases of large abdominal defects when the herniated viscera have »lost their right to reside« in the abdominal cavity; it must be remembered that surgical repair of an incisional hernia has nothing in common with closure of a laparotomy. The weakening of the abdominal wall and the consequences of decreased abdominal pressure on diaphragmatic mobility and respiratory function are important factors [3]. Surgical repair requires placement of a prosthetic mesh. Without mesh, the recurrence rate is high and prohibitive because it may vary from 30% to 60% [1]. Retromuscular prefascial placement of the mesh, which we will describe as a standard procedure, has been proposed by Rives and used in our department since 1966. Let us remember its basic principles: ▬ A macroporous mesh ▬ Placed in an extraperitoneal site ▬ With fixation by transfixing stitches ▬ Under a tension sufficient to give normal physiology to the abdominal wall ▬ With a good cosmetic result Described as early as 1973 [3], this technique was clearly demonstrated in 1977 in the French Encyclopedia of Surgery [4]. The drawings were later reproduced in the first and second editions of Chevrel’s Hernias and Surgery of the Abdominal Wall [5]. They have also been reproduced by Kingsnorth [2] and, with minor modifications, by Wantz [6], Stoppa et al. [7], and Bauer et al. [1]. This technique is considered the gold standard for repair of midline incisional hernias [8]. Clinical features are evident, and the diagnosis is obvious at the first look. The bulge is seen when the surgeon asks the patient to push or cough, increasing the abdominal pressure. Palpation identifies the edges of the musculoaponeurotic defect, but precise measurement of the defect’s dimensions may be difficult in very obese patients. Therefore,

computed tomography (CT) scanning is very useful to assess the dimensions of the defect, the retraction of the lateral muscles of the abdominal wall, and the volume of the mushroom-like mass of bowel exteriorized from the abdominal cavity [9]. As a consequence of the extraabdominal protrusion of the viscera, the decrease in intraabdominal pressure leads to general and local disturbances. The recti and lateral muscles are infolded because they have lost their midline insertion on the linea alba. Wylie [10], as early as 1887, had understood this, writing that »most operators entirely overlook the fact that the deep fascia which divides and forms the sheath of the recti muscles, and unites in the median line to form the linea alba, is in reality the tendon of the transverse abdominal muscles; that is the fascia, and not the recti muscles, which gives the abdominal walls their transverse strength.« The recti abdominis are sagittalized, and flat lateral muscles (external oblique, internal oblique, and transversus) are retracted and become fatty and sclerotic. The skin is also involved in the abdominal wall disease: Trophic ulcerations are often observed in large tumefactions. They are located over the midline and the apex of the protrusion, resulting from the weakening of the subcutaneous cellular tissue and the flattening of blood vessels due to visceral pressure [11]. Perhaps more important are the respiratory consequences related to the disappearance of the normal contribution of the abdominal muscles and diaphragm in respiration [3]. These disorders must be evaluated by appropriate respiratory function tests in order to avoid a catastrophic postoperative course. In some cases, the herniated organs have lost their »right to reside« in the abdomen, and herniation cannot be reintegrated into the abdomen. These cases require specific preparation with therapeutic preoperative pneumoperitoneum [12].

Preoperative Care On initial contact with the patient, respiratory function must be assessed (history of smoking, cough, expectorations). Preparation includes respiratory physiotherapy, withdrawal of tobacco, and, if possible, weight loss. In cases of hernias with

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loss of domain, as evaluated by preoperative CT scanning [9], the technique of preoperative therapeutic pneumoperitoneum is useful. Air is injected into the peritoneal cavity until the patients feels discomfort (scapular pain). The amount of air that can be injected during each session varies greatly according to the patient, from half a liter to more than a liter. These pneumoperitoneum sessions are repeated every 2 or 3 days, and the patient is monitored with X-rays (subdiaphragmatic air images). With this technique, the patient’s tolerance to reintegration of the herniated viscera can be assessed. The diaphragm is readapted to work in physiological conditions and is able to accept the postoperative increase in intraabdominal pressure.

Surgical Treatment The objectives of the operation are to place a prosthetic material in the retromuscular prefascial space. The prosthesis must be sutured under tension. We use transfixing sutures. This procedure of fixation can lead to recuperation of lateral muscle function since the physiological tension lost because of the middle detachment of the muscle is reestablished. But when there is a risk of septic complication (opening of an old abscess, accidental opening of the bowel), the use of a nonabsorbable mesh must be forbidden. In most cases of huge incisional hernias that we deal with, there is a loss of domain because the

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herniated organs are no longer able to reside in the abdominal cavity and cannot be reintegrated into the abdomen. In this situation, there are really two abdominal cavities. This concept of a second abdominal cavity was first described by Rives et al. in 1977 [4]. CT scanning gives a clear view of the protruded viscera compared to the volume of the residual abdominal cavity [9]. A general description of the procedure can be easily given looking at a transverse cross-section of the abdominal wall (⊡ Figs. 64.1–64.4) [12, 13]. The prosthesis is placed in the rectus sheath, in contact with the muscular fibers of the rectus muscle, between the muscle and its sheath. The posterior layer of the rectus sheath, strictly closed, prevents any contact of the prosthesis with the bowel loops. Lateral fixation by transfixing stitches, placed through buttonhole stab wounds, prevents any displacement of the prosthesis and recreates the physiological tension of the lateral muscles of the abdominal wall [14]. The direction of skin incision is chosen according to the previous incision or to the major axis of the tumefaction. We usually perform a large resection of fat and skin (dermolipectomy or panniculectomy) since the hernial sac always adheres to the skin. In cases of cutaneous ulceration, the resected area should be as large as possible, extending well behind the zone of infected lymphatic reticulum [12]. After opening of the sac, adherent bowel loops, which are often present (mainly in cases of multirecurrent hernia), must be freed.

⊡ Fig. 64.1. The posterior rectus sheath is opened near the linea alba to expose the posterior layer of the rectus muscle. (From Chevrel and Flament [13], with permission from Elsevier)

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The margins of the orifice must be carefully identified. Secondary orifices must be searched for carefully (usually, these are diagnosed on sagittal three-dimensional CT scan reconstruction) and should be open; residual aponeurotic bands extending from one margin to the other have no structural value and cannot be used for repair. When the abdominal cavity is free, by liberation of bowel adhesions, the posterior rectus sheath is opened–either with a sharp knife or electrocautery–near the linea alba, to expose the posterior layer of the rectus muscle (Fig. 64.1). The area of mesh insertion must be as large as possible. Suturing the mesh to the margins of the defect offers no guarantee and usually results in hernia recurrence because of lateral detachment of the mesh. Accordingly, the mesh should extend widely beyond the limits of the myoaponeurotic orifice. An overlap of at least 5 cm is necessary. The dissection of the retromuscular space is realized with a swab or scissors. It is a blunt dissection and bloodless because it runs in an avascular space. The dissection must be pushed to the lateral margins of the rectus muscle, easily recognizable by the perforating branches of intercostal neurovascular bundles [15] (⊡ Fig. 64.2). Below the arcuate line there is no posterior layer of the rectus sheath, so the prosthesis will be placed in the so-called preperitoneal or properitoneal space (Retzius space medially, Bogros space laterally). The dissection must be careful because branches of the inferior epigastric artery cross the operative field and may cause postoperative

⊡ Fig. 64.2. The dissection is pushed to the lateral margins of the rectus muscle, easily recognizable by the perforating branches of intercostal neurovascular bundles. (From Chevrel and Flament [13], with permission from Elsevier)

hematomas if injured. In this case, they may be ligated. The dissection must be pushed to the pubic symphysis medially and to the Cooper’s ligament laterally. Thus, stitches may be passed through the Cooper’s ligament. Such stitches are a trick that takes only a few seconds and prevents any slippage of the mesh that would lead to suprapubic recurrences. This dissection may be difficult in cases of previous prostate or bladder surgery. The peritoneal cavity must be closed before the mesh is implanted. In most cases, suturing of the fascial margins can be achieved when the posterior rectus sheath has been correctly and widely freed. When fascial closure cannot be achieved, we close the defect with a patch of absorbable mesh. Omentum, when present, can also be used to protect viscera from any contact with the prosthesis; the posterior surface of the omentum allows good peritonization, while its anterior surface offers a surface of granulation tissue that granulates into the prosthesis.

Preparation of the Prosthesis The choice of prosthesis is based on the physical and biological properties of the material to be used. The ideal material must be a fairly open mesh structure so that a rapid fibroblastic response is able to invest the prosthesis, facilitating its insertion. The ideal material must also be light, with a certain degree of elasticity and suppleness; elasticity allows the prosthesis to conform freely

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to the curvatures of the visceral sac. According to the classification given by Amid [16], we use either a type III (macroporous with microporous components; Mersuture) or a totally macroporous prosthesis (Prolene). The force of the abdominal pressure holds the prosthesis against the deep surface of the muscle, achieving a sort of »suture by apposition.« However, this pressure-induced apposition is not sufficient to maintain the prosthesis correctly during the first postoperative week. Therefore, it is necessary to ensure solid peripheral suturing of the prosthetic material. Sutures are placed near the edge of the prosthesis; the two ends of a nonabsorbable stitch are passed through a fold (⊡ Fig. 64.3). To pass the stitches through the abdominal wall, we use a Reverdin needle when the subcuta-

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neous fat is very thick (as is usually the case in our patients). Each limb of the suture is passed through the abdominal wall separately, but through the same buttonhole stab wound (⊡ Fig. 64.4). In some cases when the abdominal wall is not too fatty, an ordinary stitch with a straightened needle, held by a strong needle holder, may pass through the abdominal wall, from outside to the retromuscular space previously dissected; take a bite of the prosthesis; and pass again through the abdominal wall from inside to outside. (It is interesting to note that a company, Gore & Associates, has designed a »suture passer« for celioscopic use that is very similar to a straight Reverdin needle.) So each stitch transfixes the abdominal wall twice, through a cutaneous buttonhole stab wound that will be closed at the end of the procedure by a single cuta-

⊡ Fig. 64.3. Sutures are placed near the edge of the prosthesis; the two ends of a nonabsorbable stitch are passed through a fold. (From Chevrel and Flament [13], with permission from Elsevier)

⊡ Fig. 64.4. Each limb of the suture is passed through the abdominal wall separately, but through the same buttonhole stab wound. (From Chevrel and Flament [13], with permission from Elsevier)

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neous stitch. The passage of each end of the stitch through the muscle must be separated by at least 1.5 cm. If they are closer, the muscle fibers may be cut by the knot, which may cause small lateral recurrences. The surgeon stands on the opposite side of the stitches he or she is placing. Doing so, he or she has a better view of the retromuscular space, and the tailoring of the prosthesis is easier and more precise. The transfixing sutures are placed clockwise along each semilinear line (Spiegel line) and at each extremity of the laparotomy. Twelve stitches are usually enough, but in cases of huge incisional hernia, up to 21 stitches may be used. The stitches are knotted on one side and then on the other side of the laparotomy. The tailoring of the prosthesis is important: The sutures must be placed under tension. This fixation procedure allows recuperation of lateral muscle function because the physiological tension lost by midline detachment of the muscle is reestablished (remember Wylie!). In epigastric incisional hernias, the upper part of the prosthesis is placed between the rectus abdominis anteriorly and the ribs and internal oblique posteriorly. If there is a loss of substance due to retraction of the very short muscular fibers in this location, the prosthesis may be fixed by a stitch going around the rib on each side. The surgeon must be careful not to pass the stitch through the cartilage; that may cause postoperative pain. The surgeon must also be attentive to cover the »fatty triangle« described by Conze et al. [17]. At the end of the procedure, we trim the excess prosthetic tissue. Two close suction drains are placed in contact with the prosthesis. Closure of the musculoaponeurotic layer in front of the prosthesis is always possible, thanks to the tension of the prosthesis. Two drains are placed beneath the skin. Dermolipectomy in the case of obese patients, as already mentioned, may be done for a much better cosmetic result.

Postoperative Care During the early postoperative period, respiratory physiotherapy resumes as soon as possible. Aspiration drains are monitored and are usually removed

on the 3rd or 4th postoperative day. Antithromboembolism measures must be used.

Results In a recent series of 693 nonabsorbable prosthetic repairs [18], the postoperative course was uneventful in 96.4% of the patients. Five patients died during the postoperative course, one from infection. Other deaths were from cardiac or respiratory causes. Superficial infection occurred in eight cases (1.2%). Deep infection occurred in nine patients, one being lethal, but in only one case did we have to remove the mesh. The long-term results were evaluated by careful follow-up. We observed 42 recurrences (6.7%), which were often small lateral recurrences. Thirty of them were successfully treated, leading to a final good result of 98%.

Discussion Naturally, this technique, although in our minds the best, cannot be applied to all cases; other sites of prosthetic implantation may be chosen on an anatomical basis. Intraperitoneal positioning of the prosthesis is easy, and some published studies report good results [19]. However, we do not believe that intraperitoneal implantation has any advantages, except rapidity. Of course, the peritoneum rapidly envelops the prosthesis and offers a good defense against infection without hematoma formation, but adhesions of the bowel loops to the prosthesis are frequent, thereby hindering intestinal transit and rendering reintervention dangerous. We have observed 17 cases of intraluminal migration of intraperitoneal prosthesis, and similar cases have been reported in the literature [20]. When possible, interpositioning of the omentum between the viscera and the prosthesis, as advocated by Rives et al. in 1973 [3], can provide protection against these complications. Laparoscopic placement of a prosthesis is a variant of intraperitoneal placement. We think this technique may be used for small hernias but that

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it is ineffective for large hernias because the prosthesis cannot be placed under good tension due to the pneumoperitoneum. This technique may be dangerous because dissection of the intrasaccular adhesions is difficult and may lead to bowel fistulas. Finally, laparoscopic treatment cannot give a good cosmetic result because it does not treat the problem of excess skin. Premuscular positioning of the prosthesis is another option [21]. This technique consists of closing the midline by reflected flaps of the interior layer of the rectus sheath, this suture being reinforced by a large premuscular prosthesis, usually Prolene. The problem with this technique is the necessity of lifting a huge cutaneous flap, which may lead to long-lasting seromas.

Conclusion We can say that the standard retromuscular prefascial prosthesis can be applied in about 80% of the cases we are confronted with. But an abdominal wall surgeon must know other techniques to fix the 20% of cases in which a retromuscular prosthesis cannot be used.

References 1. Bauer JJ, Harris MT, Gorfine SR et al.: Rives-Stoppa procedure for repair of large incisional hernias: experience with 57 patients. Hernia 6:120–123, 2002 2. Kingsnorth A: The management of incisional hernia. Ann R Coll Surg Engl 88:252–260, 2006 3. Rives J, Lardennois B, Pire JC et al.: Les grandes éventrations. Importance du »volet abdominal« et des troubles respiratoires qui lui sont secondaires. Chirurgie 99:547– 563,1973 4. Rives J, Pire JC, Flament JB et al.: Traitement des éventrations. In: Encyclopédie medico-chirurgicale. Techniques chirurgicales–appareil digestif. Elsevier, Paris, 1977 5. Flament JB, Rives J, Palot JP et al.: Major incisional hernia. In: Chevrel JP (ed) Hernias and surgery of the abdominal wall. Springer, Paris, 1997, pp 128–158 6. Wantz GE: Incisional hernioplasty with Mersilene. Surgery 172:129–137, 1991 7. Stoppa R, Moungar F, Verhaeghe P: Traitement chirurgical des éventrations médianes sus ombilicales. J Chir 129:335–343, 1992 8. Miedema B: Repair techniques for major incisional hernias. Am J Chir 187:148–152, 2004

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9. Pourcher G, Deguelte S, Diaz Cives A et al.: Giant incisional hernias: a new criteria for evaluation and treatment. Hernia [submitted] 10. Wylie G: Ventral hernia caused by laparotomy. Am J Obstet 20:53, 1887 11. Flament JB, Avisse C, Palot JP et al.: Trophic ulcers in giant incisional hernias–pathogenesis and treatment. A report of 33 cases. Hernia 1:71–76, 1997 12. Flament JB: Retro rectus approach to ventral hernia repair. Oper Tech Gen Surg 6:165–178, 2004 13. Chevrel JP, Flament JB: Traitement des éventrations de la paroi abdominale. In: Encyclopédie medico-chirurgicale. Editions techniques. Techniques chirurgicales–appareil digestif. Elsevier, Paris, pp 40–165, 1995 14. Flament JB, Palot JP: Prosthetic of massive abdominal ventral hernia. In: Fitzgibbons RJ, Greenburg AG (eds) Nyhus and Condon’s hernia (5th edn). Lippincott, Philadelphia, 2002, pp. 341–365 15. Flament JB: Funktionelle anatomie der bauchwand. Der Chirurg 5:401–407, 2006 16. Amid PK: Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia 1:15–21, 1997 17. Conze J, Prescher A, Klinger U, Saklak M, Shumpelick V: Pitfalls in retro-muscular mesh repair for incisional hernia: the importance of the «fatty triangle.» Hernia 8:255–259, 2004 18. Flament JB, Palot JP, Lubrano D et al.: Retromuskuläre netplastik: Erfahrungen aus Frankreich. Chirurg 73:1053– 1058, 2002 19. Arnaud JP, Cervi C, Tuech JJ et al.: Surgical treatment of post operative incisional hernias by intra-peritoneal insertion of a Dacron mesh. Hernia 1:97–99, 1997 20. Flament JB, Avisse C, Palot JP et al.: Complications in incisional hernia repairs by the placement of retromuscular prostheses. Hernia 4:525–529 (suppl 1), 2000 21. Chevrel JP: Traitement des grandes éventrations médianes par plastie en paletot et prothèse. Nouv Presse Med 8:695–696, 1979

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In Support of Individualized Procedures in Abdominal Wall Hernia Repair M. Miserez, E. Peeters, F. Penninckx

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Introduction

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This paper describes our algorithm for a tailored approach to patients with abdominal wall hernias, excluding inguinal hernias. We believe that, even more than in inguinal hernia repair, an individualised approach is most appropriate for an optimal outcome. Abdominal wall hernias include both ventral and incisional hernias. A ventral hernia is a primary abdominal wall hernia (e.g. epigastric, umbilical, Spigelian). Any hernia developing at the site of a previous incision is referred to as an incisional hernia. Many different factors (patient, hernia, surgeon, economic) play a role in the choice of the most appropriate surgical procedure for ventral or incisional hernia repair. Patient factors include risk factors for hernia development or hernia recurrence (⊡ Table 65.1), details on previous hernia repair with respect to the plane of previous mesh implantations, symptoms at the time of presentation (e.g. incarceration), and the importance of aesthetic aspects to the patient (e.g. postoperative bulge). Hernia factors include the size of the defect and hernia sac, the location of the defect (e.g. parastomal), and the presence of additional muscle diastasis or bulging around the defect. Surgeon factors imply that the surgeon should ideally have both open and laparoscopic expertise. Economic aspects refer to the cost of the new generation of meshes (including specially designed intraabdominal meshes with antiadhesive properties and »megaporous« meshes with larger pores and mostly lower weight or density than the classical macroporous meshes) and the hospital costs associated with, for example, the use of a laparoscopic procedure (laparoscopic equipment, disposable materials).

Classification and Definition In the absence of an ideal ventral/incisional hernia classification and taking into account different hernia details (e.g. defect location, diameter and surface area, patient habitus, risk factors), the Chevrel classification based on the location and width (transverse diameter) of the hernia defect currently offers the simplest, easiest system for

⊡ Table 65.1. Risk factors for hernia recurrence        

Obesity Smoking Diabetes Immunodeficiency (including cirrhosis, malnutrition, etc.) Chronic cough Prostatic hypertrophy Constipation History of abdominal aortic aneurysm

tailoring the approach to the individual patient [1]. Type 1 hernias (width <5 cm) can be described as small, type 2 hernias (width 5–10 cm) as medium, type 3 hernias (width 10–15 cm) as large, and type 4 hernias (width >15 cm) as giant [2]. The latter are sometimes accompanied by a loss of domain in the abdominal cavity. Hernia width is more important than hernia length because the possibility for approximation of the lateral edges of the hernia defect depends on this hernia width. Moreover, hernia width is often correlated with the length and thus with the overall hernia surface area. In determining the hernia defect size in incisional hernia, the size of additional defects (e.g. Swiss-cheese defects) or eventual weaknesses or bulging over the entire previous incision need to be taken into account when calculating the final defect size. Of course, the preoperative hernia diameter needs to be verified intraoperatively, and the surgical strategy may need to be modified as a result of this. When a mesh is used for hernia repair in the ventral abdominal wall, it can be placed anterior to the abdominal wall muscles (onlay), between the fascia edges (inlay or interposition), or posterior to the abdominal wall muscles [sublay if extraperitoneal and underlay or intraperitoneal onlay mesh (IPOM) technique if intraperitoneal]. (See ⊡ Fig. 65.1). Most authors agree that the current gold standard in open mesh repair is the sublay extraperitoneal repair popularised by Rives [3] and Stoppa [4]. The main disadvantage of this technique is the extensive retromuscular dissection necessary for implanting the prosthesis, which can lead to postoperative wound complications such as hematoma and seroma formation. Therefore, open onlay mesh repair, initially popularised by Chevrel [5], has been recently promoted

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⊡ Fig. 65.1. Terminology of mesh location for ventral/incisional hernia repair

again [6] and could be especially useful in locations where the retromuscular plane is more difficult to dissect (e.g. semilunar line, subcostal). Although easier than the sublay approach, it has not gained widespread acceptance because of the less physiological localisation of the mesh, in which a high intraabdominal pressure might push the mesh away from the fascia and could ultimately lead to early recurrence, especially in cases of inadequate fixation and/or overlap of the defect. Moreover, the extensive subcutaneous dissection might result in subcutaneous seroma formation and wound dehiscence. Because of the immediate contact of the subcutis with a large surface of foreign body material, mesh infection is also more likely to develop [2]. Highlevel evidence in the literature, however, is limited, and only a randomised controlled trial (RCT) with onlay vs. sublay mesh positioning as a variable will be able to solve this pertinent question. On the other hand, because of the absence of any overlap between mesh and healthy tissue, and thus a high risk for hernia recurrence, inlay repair should be abandoned. In both open onlay and sublay mesh repair, special attention should be paid to closing the anterior fascia by adapting the abdominal wall muscles and anterior rectus sheath on the midline. This reconstruction of the abdominal wall is especially

important in large and giant hernias to avoid early mesh migration (leading to an early hernia recurrence) or later bulging of the mesh with a bad aesthetic result and abnormal functioning of the abdominal wall muscles during respiration. In this case, the sutured fascia acts as an extra buttress, and a faster mesh ingrowth due to better contact with host tissue can be expected. This is referred to as mesh augmentation. In cases in which the fascia cannot be closed completely, the mesh is used (partially) as a bridge between the fascia edges (»mesh bridging«; ⊡ Figs. 65.1 and 65.2). Whether closure of the posterior rectus sheath (above the arcuate line of Douglas) before sublay mesh implantation is an important factor in preventing postoperative bulging/herniation remains unclear. We prefer to close this posterior rectus sheath as much as possible in order to create a barrier between the (polypropylene) mesh and the viscera and also to restore the original anatomical planes as much as possible.

Very Small Ventral or Incisional Hernias (≤2 cm Maximum Diameter) The data in the literature on the value of primary suture repair in small ventral or incisional hernias are very limited. Two RCTs are available. The

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⊡ Fig. 65.2. Anatomical demonstration of mesh augmentation techniques and inlay mesh positioning

first trial compared the long-term recurrence rate of a continuous suture repair (polypropylene) vs. sublay polypropylene mesh repair in 181 midline incisional hernia patients (diameter ≤6 cm) [7]. A subanalysis of small incisional hernias (hernia surface area ≤10 cm2) showed a significantly increased 10-year cumulative recurrence rate of 67% vs. 17% for the suture repair patients (p=0.003). The overall long-term complication rate (small and larger hernias), which was available for 126 patients with an average follow-up of 8 years, showed no significant difference (8% for suture repair vs. 17% for mesh repair; p=0.17). However, six patients in the mesh group developed a fistula between the mesh and the skin (n=3), a mesh infection (n=1), or an enterocutaneous fistula (n=2). Further details on the association between hernia defect and complication rate are not available. The authors concluded that suture repair should be abandoned. Another RCT compared the long-term recurrence rate (mean follow-up 64 months) after suture repair (interrupted nonresorbable suture) vs. sublay mesh repair (polypropylene mesh or plug) in primary umbilical hernia patients [8]. Here, too, the recurrence rate was significantly increased in the suture repair patients (11% vs. 1%; p=0.0015).

A subanalysis showed a recurrence rate of 10% (suture) vs. 0% (mesh) in the very small hernias (≤3 cm) and a recurrence rate of 13% (suture) vs. 3% (mesh) in the larger hernias (>3 cm) [9]. Complications in the overall group did not differ. Also in this paper, no data are given with respect to body mass index (BMI) or other risk factors for hernia recurrence. Thus, although the recurrence rate in the small hernias is clearly in favour of mesh repair in both trials, it is not entirely clear that both groups were comparable concerning risk factors for developing a recurrent hernia. Moreover, it is not certain whether the data for these small hernias with a diameter of around 3 cm (surface area of 10 cm2= diameter of 3.6 cm, provided the defect is circular) are valid for even smaller hernias with a maximum diameter the size of a finger (1.5–2 cm), this being the majority of umbilical hernias. Therefore, also taking into account the chronic risk of mesh-related complications [10], in the absence of any risk factors and without muscle diastasis around the defect, we suggest a suture repair for very small ventral (umbilical, epigastric, Spigelian) or incisional hernias (e.g. trocar site hernias).

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After all of the avascular weakened scar tissue is excised, the suture repair should preferably be performed with a one-layer nonabsorbable monofilament suture of size 0 or 1, or slowly resorbable polydioxanone. Transverse adaptation of the fascial edges without a »vest-over-pants« Mayo technique [11] is suggested.

Small and Medium-Size Ventral/ Incisional Hernias (2–10 cm Maximum Hernia Width) For these hernias we suggest an open sublay or laparoscopic IPOM mesh repair. In a retrospective analysis of 175 consecutive patients with open sublay repair and average hernia size between 8.5 cm and 10.6 cm, anterior fascial closure was associated with a decreased risk for prosthetic infection (2% vs. 26%; p<0.01). The recurrence risk after a follow-up period of 20 months was not shown to be statistically different, although recurrence rates were increased by almost threefold in the nonclosure group (16%) vs. the closure group (6%; p=0.10) [12]. With adequate mobilisation of the skin and subcutis laterally, anterior fascial closure is almost always possible in these hernias during open sublay repair. When a small gap remains, the medial edges of the anterior rectus sheath can be fixed onto the mesh, or a small polyglactin mesh can be used as an additional inlay mesh to avoid lateral retraction of these edges. Laparoscopic mesh repair has the main advantages of decreased wound complications, especially in obese patients, and a shortened hospital stay [13]. On the other hand, a laparoscopic repair involves the use of a more expensive intraabdominal antiadhesive mesh, and both postoperative acute and prolonged pain may be higher after a laparoscopic procedure. All of these parameters should be taken into account when calculating cost-effectiveness. Recurrence rates in the midterm seem to be comparable with those for open repair. However, from the available randomised trials so far, it is very difficult to draw any final conclusions because of the low patient numbers and the heterogeneity of inclusion criteria, definitions of postoperative outcome parameters, and duration and

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methods of follow-up. To answer these questions, a large RCT was initiated both in Europe and the United States. It seems that the trial in the United States, comparing open onlay repair and laparoscopic repair, was prematurely stopped because of an unacceptable number of wound complications in the open group [14]. The European LAPSIS trial, running under the auspices of the European Hernia Society, currently includes more than 200 patients and compares not only open sublay repair vs. laparoscopic repair but also, in every arm, the use of a biological mesh (Surgisis Gold) vs. a nonresorbable prosthesis. Inclusion criteria are patients with a BMI <40 and a primary or incisional hernia with a maximum diameter of 4–10 cm. All eligible patients in our department have been proposed to enter the trial. The primary end point is a composite end point of major complications at 3 years (hernia recurrence and/or mesh infection and/or reoperation related to the previous hernia repair) [15]. For all patients with a very small hernia who do not undergo suture repair and for all other patients with a maximum hernia width of 10 cm that do not fulfil the inclusion criteria for the LAPSIS trial, either a laparoscopic or an open sublay mesh repair can be offered. In the absence of further highlevel evidence-based data, we propose laparoscopic repair to the patient, especially in cases of BMI >35–40, on the condition that he or she be willing to cover the additional cost for the intraabdominal prosthesis since these costs are currently not covered by the social security system in Belgium. In a specific subgroup of these patients, we try to avoid the use of an intraabdominal prosthesis by using an endoscopic totally preperitoneal repair, as in laparoscopic totally extraperitoneal (TEP) inguinal hernia repair [16]. Good candidates for this technique are patients with a lateral incisional hernia (e.g. postappendectomy) or a hernia that is localised subxiphoidally, suprapubically, or close to other bony edges (iliac spine, costal margin). In many cases, direct contact between the mesh and the bowel can be avoided, and a simple polypropylene mesh is used. Ideally, anterior fascial closure and mesh augmentation should also be aimed at during a laparoscopic procedure, not to decrease the risk for

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prosthetic infection as in open repair but mainly to decrease the risk for early mesh migration or late bulging of the mesh. We believe this is especially true for the large and giant hernias, but it is exactly in this group of patients that this is most difficult to accomplish due to excessive tension on the tissues, even after decreasing the intraabdominal pressure of the pneumoperitoneum. Chelala et al. described excellent results (low incidence of seroma formation and chronic pain, low recurrence rate) in a large group of patients with systematic laparoscopic closure of the defect (although no closure was performed in 4.5% of cases), but it is not clear how many patients actually had a large defect [17]. Whether this closure really needs to be done in small and medium-size hernias remains to be shown [18]. In all cases, exploration of the complete scar is warranted, and additional hernias or bulging or diastases over a previous incision need to be addressed and treated as the original hernia. In the absence of any weaknesses, we use a tailored approach based on different parameters to determine the need for coverage of the whole incision in a patient with an incisional hernia [19].

Large Ventral/Incisional Hernias (10–15 cm Maximum Hernia Width) Although a laparoscopic approach is feasible [20, 21], we feel that a low chance for recurrence, together with an optimal functional and aesthetic result, can be obtained only by an open sublay repair with excision of redundant, often thinned compromised skin and a maximal attempt at anatomical reconstruction of the abdominal wall. In addition, (laparoscopic) adhesiolysis can be very cumbersome in large and giant hernias, and the mortality rate in cases of unrecognised enterotomy can be as high as 7.7% [22]. In most smaller hernias during open repair, the anterior fascia can readily be approximated on the midline, but in these larger hernias, additional relaxing incisions may be necessary to obtain this goal. Apart from decreasing the risk for prosthetic infection, this adaptation is mainly important in large and giant hernias, as men-

tioned before. The most radical relaxing incision technique is the component separation technique (CST) described by Ramirez et al. in 1990 [23]. Another possibility is multiple small relaxing incisions bilaterally on the anterior rectus sheath according to Clotteau and Premont [24] or one single relaxing incision on each anterior rectus sheath two-thirds from the midline according to Gibson [25], with or without turndown of the anterior rectus sheath according to Welti and Eudel [26]. If, however, a large defect remains at the level of the anterior fascia (mesh bridging), most authors also agree that a so-called megaporous mesh should preferably be avoided to decrease the risk for early or late bulging of this type of soft, (too) elastic prosthesis.

Giant Ventral/Incisional Hernias (>15 cm Maximum Hernia Width) This group of patients present with the most challenging hernias. For the same reasons as discussed above, we believe laparoscopic repair is not indicated. In the case of loss of domain in the abdominal cavity, a preoperative pneumoperitoneum [27] and optimal preparation of the patient (e.g. weight loss, respiratory physiotherapy, bowel preparation) may be necessary. Especially in this patient group, in whom anterior fascial closure is important for an acceptable functional and aesthetic result, this closure is at the same time the most challenging, due to retraction of the fascial edges laterally, and CST is necessary in the majority of cases. Skin coverage with a well-vascularised skin and subcuticular flap without undue tension is extremely important in this group to avoid wound dehiscence or superficial wound infection, which might be the start of a real disaster, with mesh infection and fascia disintegration. Therefore, all compromised skin tissue of bad quality needs to be excised at the end of the procedure. An extensive lateral dissection together with adequate subcutaneous drainage and avoidance of dead space on the midline are key points to preserve skin integrity at the incision during the postoperative course. To do this, a multidisciplinary approach involving the plastic surgeon to create an autolo-

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gous skin (plus fascia) flap is necessary in a subset of these patients. Due to a small part of the rectus muscle that remains, it is nearly always necessary to open the semilunar line to develop a nice extraperitoneal plane (beneath the transversus abdominis muscle) for mesh implantation; even then, it is almost impossible to close the posterior rectus sheath as a barrier between the mesh and the viscera, so a specially designed mesh with antiadhesive properties will be needed. Whether a simple and cheap polyglactin mesh acts as an equally effective antiadhesive barrier between polypropylene and the viscera remains controversial [28, 29]. In addition, Petersen et al. showed that extraperitoneal mesh implantation might even further compromise anterior fascial closure, in contrast to intraperitoneal mesh implantation [12]. Taking all of these findings together, a more straightforward intraperitoneal (underlay) mesh implantation without extraperitoneal dissection might be a better option in these patients [30], despite the inherent risks of a more extensive adhesiolysis. A third option is an onlay mesh technique in combination with CST, as was done in 18% of the

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patient population reported on by Kingsnorth et al. [6]. In such cases, it is possible to overlap the relaxing incisions with the same mesh, extending far laterally and thereby reducing the risk for abdominal wall bulging or even abdominal wall rupture [31].

Conclusion The algorithm in ⊡ Fig. 65.3 summarises our current approach based on the maximum hernia width. Of course, this algorithm is only a rough guide to quickly determine the best approach. Preoperative patient details (including the skin condition, such as thinning or ulceration) and intraoperative hernia characteristics (especially in cases of unexpected multiple hernia orifices at different locations) will influence the surgical strategy in the individual patient. Therefore, we strongly believe that the abdominal wall surgeon should master both laparoscopic and different open procedures in order to use them in a tailored way in the individual patient who presents with a ventral or incisional abdominal wall hernia.

⊡ Fig. 65.3. Algorithm for determining surgical strategy as a function of hernia width in ventral/incisional hernia repair (CST component separation technique)

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References

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1. Chevrel JP, Rath AM (2000) Classification of incisional hernias of the abdominal wall. Hernia 4:7–11 2. Korenkov M, Paul A, Sauerland S, Neugebauer E, Arndt M, Chevrel JP, Corcione F, Fingerhut A, Flament JB, Kux M, Matzinger A, Myrvold HE, Rath AM, Simmermacher RK (2001) Classification and surgical treatment of incisional hernia. Results of an experts’ meeting. Langenbecks Arch Surg 386:65–73 3. Rives J, Lardennois B, Pire JC, Hibon J (1973) Les grandes éventations. Importance du « volet abdominal » et des troubles respiratoires qui luis sont secondaires. Chirurgie 99:547–563 4. Stoppa R, Petit J, Abourachid H, Henry X, Duclaye C, Monchaux G, Hillebrant JP (1973) Original procedure of groin hernia repair: interposition without fixation of Dacron tulle prosthesis by subperitoneal median approach. Chirurgie 99:119–123 5. Chevrel JP, Rath AM (1997) The use of fibrin glues in the surgical treatment of incisional hernias. Hernia 1:9–14 6. Kingsnorth AN, Shahid MK, Valliattu AJ, Hadden RA, Porter CS (2008) Open onlay mesh repair for major abdominal wall hernias with selective use of components separation and fibrin sealant. World J Surg 32:26–30 7. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004) Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–583 8. Arroyo A, Garcia P, Perez F, Andreu J, Candela F, Calpena R (2001) Randomized clinical trial comparing suture and mesh repair of umbilical hernia in adults. Br J Surg 88:1321–1323 9. Perez F, Arroyo A (2002) Authors’ reply. Br J Surg 89:628 10. Costa D, Tomas A, Lacueva J, de Asis Perez F, Oliver I, Arroyo A, Sanchez A, Andreu J, Gallego JA, Calpena R (2004) Late enterocutaneous fistula as a complication after umbilical hernioplasty. Hernia 8:271–272 11. Mayo WJ (1901) An operation for the radical cure of umbilical hernia. Ann Surg 34:276–280 12. Petersen S, Henke G, Zimmerman L, Aumann G, Hellmich G, Ludwig K (2004) Ventral rectus fascia closure on top of mesh hernia repair in the sublay technique. Plast Reconstr Surg 114:1754–1760 13. Sajid MS, Bokhari SA, Mallick AS, Cheek E, Baig MK (2009) Laparoscopic versus open repair of incisional/ventral hernia: a meta-analysis. Am J Surg 197:64–72 14. Itani KM, Neumayer L, Reda D, Kim L, Anthony T (2004) Repair of ventral incisional hernia: the design of a randomized trial to compare open and laparoscopic surgical techniques. Am J Surg 188:22S–29S 15. Sauerland S, Miserez M, Grass G, Stützer H, Neugebauer E (2004) LAPSIS: a randomised controlled multicentre trial of laparoscopic versus open ventral hernia repair using a classical versus a collagen mesh (Surgisis Gold). Langenbecks Arch Surg 389:429

16. Miserez M, Penninckx F (2002) Endoscopic totally preperitoneal ventral hernia repair. Surg Endosc 16:1207–1213 17. Chelala E, Thoma M, Tatete B, Lemye AC, Dessily M, Alle JL (2007) The suturing concept for laparoscopic mesh fixation in ventral and incisional hernia repair: mid-term analysis of 400 cases. Surg Endosc 21:391–395 18. Agarwal BB, Agarwal S, Gupta MK, Mishra A, Mahajan KC (2008) Laparoscopic ventral hernia meshplasty with »double-breasted« fascial closure of hernial defect: a new technique. J Laparoendosc Adv Surg Tech A 18:222– 229 19. Miserez M, Tomczyk K, Penninckx F (2007) The local patch. In: Schumpelick V, Fitzgibbons RJ (eds) Recurrent hernia: prevention and treatment. Springer, Heidelberg, pp 226–232 20. Kirshtein B, Lantsberg L, Avinoach E, Bayme M, Mizrahi S (2002) Laparoscopic repair of large incisional hernias. Surg Endosc 16:1717–1719 21. Ferrari GC, Miranda A, Sansonna F, Magistro C, Di Lernia S, Maggioni D, Franzetti M, Pugliese R (2008) Laparoscopic management of incisional hernias > or = 15 cm in diameter. Hernia 12:571–576 22. LeBlanc KA, Elieson MJ, Corder JM 3rd (2007) Enterotomy and mortality rates of laparoscopic incisional and ventral hernia repair: a review of the literature. JSLS 11:408–414 23. Ramirez OM, Ruas E, Dellon AL (1990) »Components separation« method for closure of abdominal-wall defects: an anatomic and clinical study. Plast Reconstr Surg 86:519– 526 24. Clotteau J, Prémont M (1979) Treatment of severe median abdominal cicatricial eventrations by an aponeurotic plastic procedure. Chirurgie 105:344–346 25. Gibson CL (1920) Operation for cure of large incisional hernia. Ann Surg 72:214–217 26. Welti H, Eudel F (1941) Un procédé de cure radicale des éventrations postopératoires par auto-étalement des mucles grands droits après incision du feuillet antérieur de leur gaine. Mem Acad Chir 12:791–798 27. Goni Moreno IG (1947) Chronic eventrations and large hernias. Surgery 22:945–948 28. Jenkins SD, Klamer TW, Parteka JJ, Condon RE (1983) A comparison of prosthetic materials used to repair abdominal wall defects. Surgery 94:392–398 29. de Vries Reilingh TS, van Goor H, Koppe MJ, Bodegom ME, Hendriks T, Bleichrodt RP (2007) Interposition of polyglactin mesh does not prevent adhesion formation between viscera and polypropylene mesh. J Surg Res 140:27–30 30. Bernard C, Polliand C, Mutelica L, Champault G (2007) Repair of giant incisional abdominal wall hernias using open intraperitoneal mesh. Hernia 11:315–320 31. de Vries Reilingh TS, Bleichrodt RP (2007) [Reply to letter to the editor.] World J Surg 31:2267–2268

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Discussion Kurzer: Dr. Flament, have you ever seen a hernia that you thought was inoperable, that you couldn’t operate on? Flament: Yes. There are some people—old patients, with fistula and a short life expectancy; in these cases we do not operate. But in young patients with loss of domain, we perform a progressive pneumoperitoneum; we could always reintegrate all of the abdominal cavity. And in very rare cases we perform a resection, for example, a left hemicolectomy to close the abdominal wall. Deysine: A comment on the small hernias below 2 cm, which are most common. My experience at the VA Hospital doing these little hernias with conventional suture repair was a recurrence rate of 100%. The motion of the abdominal wall when the patient stands up is so strong that it will break it. Since I began using small pieces of mesh, sometimes the tip of a plug, just to obliterate those little holes, the recurrences went away. Schumpelick: Maybe this should be studied in a trial. I also believe that small trocar hernias can be done by stitches with good results.

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In Support of Standard Procedure in Hiatal Hernia Repair P. K. Chowbey, T. Mittal, V. Soni, R. Khullar, A. Sharma, M. Baijal, A. Dey

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Introduction

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Laparoscopic esophageal surgery has gained popularity due to the unprecedented view it allows of esophageal hiatal hernias and the ease of access to the surgical site offered by the minimal-access approach. Numerous series have demonstrated the safety and efficacy of approaching gastroesophageal reflux disease (GERD) and hiatal hernia repair laparoscopically [1, 2]. Despite increasing experience with laparoscopic hiatal hernia repair, authors continue to report recurrence rates of up to 43% with sutured cruroplasty [3, 4]. This compares laparoscopic hiatal hernia repair poorly with open repair, as it is well documented that open hiatal hernia repair with the addition of Stamm gastrostomy is associated with very low recurrence rates [5, 6]. Additionally, intrathoracic wrap migration rates of up to 26% have been reported for patients undergoing laparoscopic fundoplication with primary sutured hiatal hernia repair [7]. Some possible patient-related and procedurerelated mechanisms for recurrence include inappropriate patient activity immediately after surgery, inadequate excision of the sac, inadequate mobilization of the esophagus, inadequate crural closure secondary to widely spaced crura sutured under tension, and postoperative rupture of the cruroplasty due to continuous excursion of the diaphragm. Several technical details have been considered to minimize these high recurrence rates, including excision of the sac with complete detachment of the sac from the hiatus and mediastinum, adequate mobilization of the esophagus with a minimum of 3 cm of intraabdominal esophagus, and the use of mesh cruroplasty in patients with large hiatal hernias. The purpose of using prosthetic materials is to achieve a tension-free hiatal repair. The mesh may be used to close the gap between two widely spaced crura or to reinforce a suture cruroplasty. There has been debate regarding the type, size, and shape of mesh and the technique of mesh placement; these are matters of future research in this field. The aim of the present study was to evaluate the effect of mesh reinforcement in laparoscopic

hiatal hernia repair on recurrence rate and side effects during long-term follow-up.

Materials and Methods Patients A total of 430 patients (165 men and 265 women) underwent laparoscopic hiatal hernia repair between January 1994 and December 2007 at Sir Ganga Ram Hospital, Delhi, India. Their mean age was 42.4 years (range 25–72 years). In the period between 1994 and 2002, suture cruroplasty was performed for most of the patients with hiatal hernias, except for those with a very wide hiatal defect in whom the crura could not be brought together with sutures. In those patients, mesh cruroplasty was performed. After 2002, crural repair was reinforced by using a mesh for hiatal hernias (>5 cm hernial defect) as routine practice.

Preoperative Investigation Preoperative evaluation included a chest X-ray, upper gastrointestinal endoscopy, and barium swallow for all patients. Manometry and 24-h pH monitoring were not routinely performed. Fluoroscopic evaluation provided a reasonable measure of esophageal motility. The presence or absence of dysphagia was considered another reasonably sound predictor of whether the patient would tolerate full fundoplication. An antireflux procedure was performed in most circumstances.

Indications for Surgery Sliding hernia: All symptomatic patients Paraesophageal hernia: Even asymptomatic patients were operated on to avoid the potential risk of life-threatening complications such as incarceration, volvulus, perforation, and bleeding. Exclusion criteria: Patients with symptoms of GERD without hiatal hernia

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Surgical Technique

Ports

Our aims of surgery are as follows: ▬ Reduction of contents ▬ Excision of the sac ▬ At a minimum, a 3-cm intraabdominal length of esophagus ▬ Division of the short gastric vessels to mobilize the gastric fundus ▬ Tension-free sutured crural repair in a hiatus <5 cm wide ▬ Prosthetic repair of the crural gap in a hiatus >5 cm wide ▬ A short, floppy 360° wrap

The camera port (10 mm or 5 mm) is made above the umbilicus, one-third of the distance between the umbilicus and the epigastrium toward the left of the midline. Additional ports, three 5-mm and one 10-mm, are placed as shown in ⊡ Fig. 66.2. The 5-mm port in the epigastrium is used to retract the left lobe of the liver using a Nathanson liver retractor (our preferred method). In some cases we also use a fan retractor for retraction of the liver. The 5-mm port in the right midclavicular line and the 10-mm port in the left midclavicular line are the surgeon’s left-hand and right-hand working ports, respectively.

Anesthesia

Reduction of Contents

The procedure is performed under general anesthesia with endotracheal intubation.

With the use of atraumatic bowel graspers, the stomach is grasped and retracted, and the contents from the hernial sac are then reduced (⊡ Fig. 66.3).

Position The patient is placed in reverse Trendelenburg position with the knees slightly flexed. The surgeon stands between the patient’s legs. The camera assistant is positioned to the right of the patient and the assistant surgeon to the left of the patient (⊡ Fig. 66.1).

Excision of Sac A right diaphragmatic crus is identified after dividing the gastrohepatic ligament (⊡ Fig. 66.4), preserving the hepatic branch of the vagus in most cases. Ultrasonic coagulating shears (UltraCision; Ethicon Endo-Surgery, Cincinnati, OH, USA) are

⊡ Fig. 66.1. Operating theater layout

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66 ⊡ Fig. 66.4. Gastrohepatic ligament being divided to visualize the right crus

⊡ Fig. 66.2. Port positions

Esophagus Mobilization Circumferential esophageal mobilization is done using ultrasonic shears so as to have a minimum of 3 cm of intraabdominal esophagus around which the fundal wrap is created. In our experience, it has been possible to mobilize the esophagus to achieve an intraabdominal length of 3 cm in all cases, and we have not felt the need to perform an esophageal lengthening procedure.

Division of Short Gastric Vessels The short gastric vessels are divided to mobilize the gastric fundus, using ultrasonic coagulating shears, until the left crus is identified (⊡ Fig. 66.5). This helps us in creating loose, floppy fundoplication. ⊡ Fig. 66.3. Stomach being reduced from mediastinum using bowel grasper

used to divide the peritoneum at the anterolateral edge of the hiatus. The natural tissue plane that exists between the peritoneal and pleural layers of the hernial sac is developed, and the sac is separated completely. Once the complete dissection of the sac has been performed, the sac is excised close to its attachment to the gastroesophageal junction and removed so that it does not interfere with subsequent repair.

Cruroplasty The retroesophageal window is enlarged, and then the esophagus is retracted to the patient’s left with a sling made with a Penrose drain or umbilical tape. The size of the hiatus is then assessed in the anterior–posterior plane (⊡ Fig. 66.6). If the size of the hiatus is <5 cm, a primary posterior suture cruroplasty is performed using two or three intracorporeal sutures (2-0 Ethibond; Ethicon, Somerville, NJ, USA) for crural approximation. Sutures are tied loosely so as not to strangulate the muscle fibers. A sufficient gap is left between the crura by visual impression to allow

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⊡ Fig. 66.5. Greater curvature of the stomach being mobilized by dividing the short gastric vessels using ultrasonic coagulating shears

⊡ Fig. 66.7. 2–0 Ethibond suture being used to fix the crural soft mesh near the right crus

⊡ Fig. 66.6. The size of the hiatus is assessed in the anterior– posterior plane

⊡ Fig. 66.8. Gastrogastric suture with 2–0 Ethibond for fundal wrap

passage for a food bolus and thereby prevent dysphagia. We prefer to err on the side of a wider hiatus in place of tight closure. Tight closure may lead to intractable dysphagia, which might not respond to any other measure and may need reexploration and removal of sutures. If the size of the hiatus is >5 cm, a mesh repair is performed either to reinforce a sutured repair or to bridge the gap between the widely spaced crura. Before placing the mesh we prefer to approximate the crura posteriorly as much as can be achieved without tension. In our initial practice, we used polypropylene mesh (Prolene; Ethicon).

There has been concern about using polypropylene mesh because it causes dense fibrosis, so later we started using lightweight meshes, UltraPro (Ethicon) and CruraSoft (Bard, Murray Hill, NJ, USA). The CruraSoft is a V-shaped mesh that conforms to the hiatal anatomy. The mesh is fixed using 2-0 Ethibond (Ethicon) sutures (⊡ Fig. 66.7), with its margins overlapping the crural margin by 2–3 cm. The gastric fundus is wrapped around the lower esophagus to create a tension-free wrap. Two gastrogastric seromuscular sutures are placed, which include a seromuscular bite on the esophageal wall to ensure correct positioning of the fundoplication and prevent slippage (⊡ Fig. 66.8). We

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routinely perform Nissen 360° fundoplication in most patients, but in patients with a history of dysphagia, detected motility disorder, and age >65, we perform partial fundoplication.

cruroplasty group were lost to follow-up. There was no conversion to open surgery.

Postoperative Management

The intraoperative complication rate was 5.81% (25 patients). Ten (2.32%) patients had a pleural tear, which was managed by positive pressure ventilation during carbon dioxide desufflation to ensure lung expansion. There were no postoperative sequelae. Ten (2.32%) patients had bleeding from the short gastric vessels, which was managed by the application of clips, and in five (1.16%) patients there was splenic capsule laceration, which was managed by compression. No splenectomy was required in any of our patients. In all patients, an adequate intraabdominal length of esophagus was achieved by mobilizing the esophagus. No patient required a gastroplasty. The postoperative morbidity was 2.7% (12/430). Three (0.06%) of our patients developed complete dysphagia (inability to swallow saliva). All of these patients were managed conservatively on intravenous fluids and cessation of all oral intake. Five (1.16%) patients developed atelectasis, and four (0.9%) had pneumonia that responded to intravenous antibiotics and chest physiotherapy. There was no mortality. The mean duration of hospitalization was 3.2 days (range 2–9 days). Postoperatively, patients with suture cruroplasty had a dysphagia rate of 9.9% (34 patients out of 342) compared with 14.7% (10/68) in the mesh cruroplasty group at 3 months after surgery (p=0.344). However, the dysphagia rate at the 1-year follow-up had improved in both groups and was not significantly different between the groups (3.8% vs. 4.4%; p=0.916). (See ⊡ Fig. 66.10.) Radiologic follow-up evaluation showed a hiatal hernia recurrence rate of 14.9% (51/342) in patients with suture cruroplasty (⊡ Fig. 66.11). Of these 51 patients, 12 were symptomatic. They were initially managed medically; however, three of these 12 patients required redo surgery. In all three patients, we found a hiatal disruption with intrathoracic migration of the fundal wrap. During follow-up of mesh cruroplasty patients, the recurrence rate was 5.8% (4/68; ⊡ Fig. 66.12)

Postoperatively, patients are kept on a liquid diet on the1st postoperative day and gradually started on a soft diet, progressing to a normal diet as tolerated. They are advised to chew their food well and not to take large bites. All tablets are given in a crushed form. We do not routinely recommend a Gastrografin study before starting a diet for the patient. Follow-up evaluations took place at 7 days, 3 months, and 1 year after surgery. A barium swallow was performed at 3 months and 1 year after surgery. Endoscopy was suggested for routine follow-up but was refused by most of our patients in view of the invasiveness of the procedure. However, it was done if the patient became symptomatic.

Surgical Outcome Preoperative data were collected retrospectively. Long-term follow-up assessment was prospectively performed for 410 patients (95%) using a standardized questionnaire. Hiatal hernia recurrence was assessed using barium swallow .The mean follow-up period was 5.6 years (range 1–13 years).

Statistical Analysis Statistical analysis was performed using, as appropriate, a chi-square test and Fisher’s exact test. A pvalue <0.05 was considered statistically significant.

Results In 357 patients we repaired the hiatus with sutured cruroplasty and in 73 patients with mesh cruroplasty (⊡ Fig. 66.9). Fifteen patients in the sutured cruroplasty group and five patients in the mesh

Intraoperative Considerations

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⊡ Fig. 66.9. Total number of patients undergoing hiatal hernia repair with and without mesh

⊡ Fig. 66.11. Recurrence rate in the suture cruroplasty group

⊡ Fig. 66.10. Incidence of dysphagia in patients with suture cruroplasty at 3 months and 1-year follow-up

⊡ Fig. 66.12. Recurrence rate in the mesh cruroplasty group

compared with 14.9% in the suture cruroplasty group (p=0.071). All of these patients had a small sliding hernia on radiologic evaluation. These patients were asymptomatic and are being regularly followed up. Most of these recurrences (three out of four) were observed in the earlier patients. Since 2005, there has been no recurrence during follow-up. No mesh-related complications were observed.

Discussion The past 50 years have witnessed a paradigm shift in the surgical repair of both inguinal and ventral hernias. Several reports of randomized data show a clear superiority of tension-free mesh hernia repair for both inguinal and ventral hernias [8–10]. Creating a tension-free, primary sutured repair of the diaphragmatic hiatus is difficult. It is a dynamic area due to diaphragmatic excursions with

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constant motion, even at rest. Nevertheless, the goal for repair of the hiatus should be to create a tension-free repair. A high recurrence rate after laparoscopic primary sutured cruroplasty, especially for large hiatal hernias [3, 4], suggests that suture repair alone does not provide an optimal tension-free repair. Our own experience demonstrated a higher recurrence rate in patients with sutured cruroplasty compared with those receiving mesh cruroplasty (14.9% vs. 5.8%). As with hernia repair in other parts of the body, there is no consensus on the best prosthetic material to use for the procedure. The most commonly used mesh is polypropylene (Prolene; Ethicon) [11–13]. Several different types of polytetrafluoroethylene (PTFE) and PTFE composite materials have been used, including DualMesh (Gore, Flagstaff, AZ, USA) [14] and a simple PTFE patch [15, 16]. Porcine small intestinal mucosa (Surgisis; Cook Surgical, Bloomington, IN, USA), which provides scaffolding for natural tissue ingrowth, is also used [17]. In our initial 27 cases, we used Prolene mesh because it is readily available, inexpensive, malleable, and easy to handle. There has been concern about the use of polypropylene mesh because it causes dense fibrosis. As a result, we have started using lightweight, large-pore meshes–Ultrapro (Ethicon) and CruraSoft (Bard)–because they are tissue friendly and known to cause less fibrosis. The hiatal meshes are available in variable shapes, including a V-shape, a U-shape, and a

⊡ Fig. 66.13. Techniques of mesh cruroplasty

completely circular mesh. There has been some concern about the use of a circular mesh because of its potential to cause circumferential fibrosis around the esophagus, resulting in dysphagia. Our preference is a V-shaped mesh (CruraSoft) for closing the esophageal hiatus. The technique for placing prosthetic materials can be either posterior, anterior onlay, or interpositional when reapproximation of the hiatus is possible (⊡ Fig. 66.13). Most surgeons prefer primary sutured repair of the hiatus followed by an onlay of prosthetic materials posteriorly. The overall theme remains that hiatal hernia repair should be made as tension-free as possible, whether via an onlay repair or an interpositional repair. Our preference is to do an onlay repair for large hiatal hernias (>5 cm). The mesh is fixed at the hiatus using sutures, tacks (not our choice), or, recently, fibrin sealant. The topographic vicinity of the heart and other major anatomical structures (liver, inferior vena cava) and the fact that the diaphragm is very thin in this area makes suturing technically difficult and requires surgical expertise. An easier alternative is to apply tacks, but this has resulted in fatal complications, including death by cardiac tamponade [18]. The use of a fibrin sealant for mesh fixation was reported by Katkhouda et al. in an animal experiment [19]. These authors were able to show that fixation with fibrin sealant is mechanically equivalent to stapler fixation. In a number of clini-

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cal studies, both the efficiency of fibrin sealant and also a reduction in postoperative complications have been shown in inguinal hernia repair [20, 21]. The use of fibrin sealant is now also being described for hiatal hernia repair. As protocol, we prefer sutures for fixing the mesh but have on occasion used fibrin sealant and found it to be a safe and effective adhesive. Higher rates of dysphagia have been reported in patients with mesh cruroplasty [22, 23], and there have been case reports of patients being reoperated for mesh-induced fibrosis [24, 25]. In most studies, the early results have shown a higher rate of dysphagia in patients with mesh cruroplasty, but this rate became comparable at 1 year of follow-up. In our study, the dysphagia rate was also comparable at 1-year follow-up (3.8% vs. 4.3%). Another major concern of using mesh at the hiatus is erosion of the mesh into the esophagus or stomach. Erosion of mesh is very rare and has been reported only in case reports [26, 27]. In our experience, there were no mesh-related complications.

Summary Reinforcement of the esophageal hiatus with a prosthetic mesh has proven to be a safe and effective procedure to reduce postoperative hiatal hernia recurrence. A few comparative studies of laparoscopic hiatal closure with simple sutures versus mesh cruroplasty have shown that patients with prosthetic hiatal closure have a lower rate of hiatal hernia recurrence in comparison to patients with simple hiatal repair. However, some patients with prosthetic hiatal closure suffer from prolonged postoperative symptoms such as dysphagia. Fortunately, this resolves in most patients without further treatment. A true complication related to the use of prosthetic materials for hiatal closure is rare.

Acknowledgments I am thankful to Dr. Tarun Mittal and Dr. Ashish Dey, my colleagues in the Minimal Access, Metabolic & Bariatric Surgery Centre, for ac-

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tively participating in the »pro standard procedure in hiatal hernia repair« project and in preparing this article. I am thankful to my colleagues Dr. Rajesh Khullar, Dr. Anil Sharma, Dr. Vandana Soni, and Dr. Manish Baijal for their invaluable assistance in completing this project. I am grateful for their constant and positive support in all the ongoing projects and progress made in the Centre. I express great appreciation to all my fellows and resident doctors, Dr. Kshipra Dhawan and Dr. Neeraj Garg, for their supportive help and efforts. I sincerely thank Ms. Aenu Batra, Mr. Pankaj Gupta, Ms. Shradha Verma, Mr. Satish Jha, and Dhuruvendra Singh for their excellent secretarial help and support.

References 1. Arnaud JP, Pessaux P, Ghavami B, Flaments JB, Trebuchet G, Meyer C, Huten N, Champauck G (2000) Laparoscopic fundoplication for gastroesophageal reflux: multicenter study of 1470 cases. Surg Endosc 14:1024–1027 2. Huntington TR (1997) Short-term outcomes of laparoscopic paraesophageal hernia repair: a case of 58 consecutive patients. Surg Endosc 11:894–893 3. Hashemi M, Peters JH, Deemeester TR, Huprich JE, Quek M, Hagen JA, Crookes PF, Theisen I, De Meester SR, Sillin F, Bremner CG (2000) Laparoscopic repair of large type III hiatal hernia: objective follow up reveals high recurrence rate. J Am Coll Surg 190:553–561 4. Wiechmann RJ, Ferguson MK, Nauheim KS, McKesey P, Hazelrigg SJ, Santucci TS, Macherey RS, Landreneau RJ (2001) Laparoscopic management of giant paraesophageal hernia. Ann Thoracic Surg 71:1080–1087 5. Schauer PR, Ikramuddin S, McLaughlin RH, Graham TO, Slivka A, Lee KK, Schraut WH, Luketich JD (1998) Comparison of laparoscopic versus open repair of paraesophageal hernia. Surg 176:659–665 6. Wichterman K, Geha AS, Cahow CE, Raue AE (1979) Paraesophageal hiatus hernia with intrathoracic stomach and colon: the case for early repair. Surgery 86:497–506 7. Granderath FA, Schweiger UM, Kamoiz T, Ashe KU, Pointner R (2006) Laparoscopic Nissen fundoplication with prosthetic hiatal closure reduces postoperative intrathoracic wrap herniation. Arch Surg 140:40–48 8. Burger JW, Luijendijk RW, Hop WC, Halm JA, Verdaasdonk EG, Jeekel J (2004) Long-term follow up of a randomized controlled trial of suture versus mesh repair of incisional hernia. Ann Surg 240:578–585 9. Lichtenstein IL, Shulman AG, Amid PK, Montlior MM (1989) The tension-free hernioplasty. Am J Surg 157:188–193

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10. Vrijland WW, van den Tol MP, Luijendijk RW, Hop WC, Busschback JJ, de Lange DC, van Geldere D, Rottier AB, Vegt PA, IJzermans JN, Jeekel J (2002) Randomized clinical trial of nonmesh versus mesh repair of primary inguinal hernia. Br J Surg 89:293–297 11. Basso N, De Leo A, Genco A, Rosato P, Rea S, Spaziani E, Primavera A (2000) 360° laparoscopic fundoplication with tension-free hiatoplasty in the treatment of symptomatic gastroesophageal reflux disease. Surg Endosc 14:164–169 12. Basso N, Rosato P, De Leo A, Genco A, Rea S, Neri Y (1999) »Tension-free« hiatoplasty, gastrophrenic anchorage and 360° fundoplication in the laparoscopic treatment of paraesophageal hernia. Surg Laparosc Endosc 9:257–262 13. Hawasli A, Zonca S (1998) Laparoscopic repair of paraesophageal hiatal hernia. Am Surg 64:703–710 14. Frantzides CT, Madan AK, Carlson MA (2002) A prospective randomized trial of laparoscopic polytetrafluoroethylene (PTFE) patch repair vs. simple cruroplasty for large hiatal hernia. Arch Surg 137:649–652 15. Athanasakis H, Tzortzinis A, Tsiaoussis J (2001) Laparoscopic repair of paraesophageal hernia. Endoscopy 33:590–594 16. Carlson MA, Richards CG, Frantzides CT (1999) Laparoscopic reinforcement of hiatal herniorrhaphy. Diag Surg 16: 407–410 17. Oelschlager BK, Barreea M, Chang L, Pellegrini CA (2003) The use of small intestine submucosa in the repair of paraesophageal hernias: initial observations of a new technique. Am J Surg 186:4–8 18. Kemppainen E, Kiviluoto T (2000) Fatal cardiac tamponade after emergency tension-free repair of a large paraesophageal hernia. Surg Endosc 14:593 19. Katkhouda N, Mavor E, Friedlander MH, Mason RJ, Kiyabu M, Grant SW, Achanta K, Kirkman EL, Narayanan K, Essani R (2001) Use of fibrin sealant for prosthetic mesh fixation in laparoscopic extraperitoneal inguinal hernia repair. Ann Surg 233:18–25 20. Lau H (2005) Fibrin sealant versus mechanical stapling for mesh fixation during endoscopic extraperitoneal inguinal hernioplasty. Ann Surg 242:670–675 21. Novik B, Hagedorn S, Mork UB, Dahlin K, Skullman S, Dalenback J (2006) Fibrin glue for securing the mesh in laparoscopic totally extraperitoneal inguinal hernia repair. Surg Endosc 20:462–467 22. Granderath FA, Schweiger UM, Kamolz T, et al. (2002) Laparoscopic antireflux surgery with routine mesh-hiatoplasty in the treatment of gastroesophageal reflux disease. J Gastrointestinal 6:347–353 23. Kamolz T, Granderath FA, Bammer T, Pasiut M, Pointner R (2002) Dysphagia and quality of life after laparoscopic Nissen fundoplication in patients with and without prosthetic reinforcement of the hiatal crura. Surg Endosc 16:572–577 24. Edelman DS (1995) Laparoscopic paraesophageal hernia repair with mesh. Surg Laparosc Endosc 5:32–37 25. Trus TL, Bax T, Richardson WS, Branum GD, Mauren SJ, Swanstrom LL, Hunter JG (1997) Complications of la-

paroscopic paraesophageal hernia repair. J Gastrointest Surg 1:221–228 26. Carlson MA, Condon RE, Ludwig KA (1998) Management of intrathoracic stomach with polypropylene mesh prosthesis reinforced transabdominal hiatus hernia repair. J Am Coll Surg 187:227–230 27. Schauer PR, Ikramudin S, McLaughlin RH, Graham TO, Slivka A, Lee KK, Schrayt WH, Luketich JD (1998) Comparison of laparoscopic versus open repair of paraesophageal hernia. Am J Surg 176:659–665

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Strategy To Improve the Results? In Support of Individualized Procedures in Hiatal Hernia Repair J. F. Kukleta

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Introduction

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It has recently become evident that the durability of crural repair determines not only the outcome quality of paraesophageal hernia (PEH) repairs but the long-term success of antireflux procedures as well. Because of the personal experience of individual surgeons and surgical teams with the complexity of hiatal repairs, several different techniques have been proposed to correct this diaphragmatic disorder. The results of the surgical treatment are far from being excellent solutions for all patients for all esophageal and extraesophageal symptoms, but in general, they promise good or satisfactory outcomes approximately 85–90% of the time. Since the introduction of laparoscopic techniques in hiatal repair, the problematic cure has become even more complex, partly due to the learning curve for everyone. Several reviews of the available published data on the hiatal environment [1–3] are quite representative of the status quo: The procedures are not standardized, and data with high levels of evidence are lacking. There are too many controversies and very little consensus. The recurrence rate of a laparoscopic simplesutured PEH repair ranges from 0% to over 40% [4]. The most important mechanism of failure of antireflux procedures is, in 60–84% of cases, migration of the intrathoracic wrap [5, 6]. Both failures are sequelae of insufficient closure or disruption of the crural repair. Unlike in endoscopic repairs for inguinofemoral or abdominal wall hernias, in which the use of prosthetic meshes is a well-accepted part of a successful tension-free repair concept, the use of meshes in hiatal repairs is still under debate [3]. To improve the results of hiatal disorders, the causes of failure must be analyzed, the predictors taken into account, and the »pillars of the best outcome« identified and reinforced. If the risk of repair failure is anticipated, then individual adaptation of the surgical technique can help prevent this situation.

Concept The objective of the following analysis of available published experiences is to highlight the con-

troversies, identify potential improvements of the surgical technique, and reinforce the position of an advocate of patient-related, individualized procedures for hiatal hernia repair in order to improve outcomes.

Material For many years it was thought that reflux and all its sequelae could be controlled by a tight wrap to increase the lower esophageal sphincter pressure and prevent the reflux [7]. A high incidence of moderate to severe dysphagia and inability to belch was the consequence. The formation of a shorter and floppy fundoplication evolved as a logical answer to a recognized inadvertent complication. Today the successful control of reflux is related to restoring adequate length of the abdominal esophagus, bringing the gastroesophageal junction back into the positive intraabdominal pressure environment, creating a floppy full wrap or partial wrap, and preventing intrathoracic wrap migration by achieving a durable crural repair. The partial wrap (Toupet [8]) was believed to be less efficient in preventing the reflux but more reliable in preventing dysphagia. Therefore, this technique was recommended to be used in patients with additional motility disorders of the distal esophagus. Some of the above-mentioned beliefs could not be confirmed in prospective controlled trials, which brought up additional doubts about the correctness of our pathophysiological understanding [9]. The successful application of prosthetic meshes in the cure of groin and abdominal wall hernias influenced the treatment of large hiatal hernias of types II–IV [10]. Various mesh materials were used to either reinforce the sutured crural repair or to cover the large nonsutured defect in a tensionfree manner. The few sporadic reports on late mesh-related complications [11–14], regardless of the material used, raised an ongoing discussion on risks and benefits, in which gut feelings and low scientific evidence were used to try to convince one another. The incidence of mesh-related complications is obviously underreported. The majority of existing studies are retrospective, and data of higher levels of evidence are scarce.

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Analysis of the causes of recurrence contributes to better understanding of the pathogenesis and enables possible correction of the operative technique [15]. Among the factors predicting repair failure, lack of surgical expertise is one of the most important. Once again, it seems to be difficult to differentiate whether the surgeon’s experience and expertise or a successful therapeutic concept has a more significant impact on outcome.

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Basso et al. improved their recurrence rate of 9% of sutured crurorrhaphy to 0% when they reinforced their sutured crural repairs with a posterior buttressing polypropylene mesh [19]. Granderath et al. [20] reviewed 42 studies regarding prosthetic hiatal closure. Mesh repairs markedly reduced the recurrence rates both in paraesophageal and antireflux surgery, with low complication rates. The mesh material and its size and shape are still controversial [20].

Arguments Risk of Mesh-Related Complications Main Problem–Crural Repair Failure Champion and McKernan [16] prospectively measured hiatal diameters in 476 primary laparoscopic antireflux procedures. The smaller defects (<4.5 cm) led to a recurrence rate of 0.9%. The bigger ones (>5 cm) showed recurrence in 10.6% of cases. The difference is highly significant: p< 0.000001. The size of the hiatus matters. In 2001 Carlson and Frantzides [6] published a review of 10,735 reported cases of minimally invasive antireflux procedures. The most common finding at redo operation for the failed repair was an intrathoracic wrap herniation due to ruptured crural closure [5, 6].

Mesh Reinforcement Reduces the Recurrence Rate in Hiatal Repair The literature review by Johnson et al. [2] on the use of mesh in hiatal repair demonstrates a highly significant reduction in recurrence rate in antireflux and PEH procedures when mesh was used either to reinforce the sutured repair or as a true tension-free repair. Champion and Rock [17] reduced their recurrence rate in laparoscopic sutured crural repair from 10.6% to 1.9% by employing a polypropylene mesh to reinforce the sutured repair in 52 patients. Frantzides et al. [18] presented a randomized controlled study comparing laparoscopic sutured cruroplasty and expanded-polytetrafluoroethylene-reinforced sutured cruroplasty. The recurrence rate of 22% improved to 0% in mesh repair.

Very few reports have been published on prosthetic complications such as erosion, stenosis, penetrations, and migrations [11–14]. Although these incidents are surely underreported, their numbers are too small to justify a general reluctance to use mesh in high-risk repairs. Even though the majority of published results report no erosions, longer follow-up is necessary because some complications of a similar type (pledget erosion) may not appear until after more than 6 years [21, 22]. To avoid the lifelong risk of potential complications from permanent prosthetic material, a new category of reinforcing biomaterials has been proposed [23]. However, the role of the various acellular scaffolds of human or porcine/ bovine origin is unclear and their value still unpredictable.

Does the 360° Wrap Control Reflux Better Than the Partial Wrap? Strate et al. [9] randomized 100 Nissen and 100 Toupet procedures with and without preoperative esophageal motility disorders. After 2 years, the patients with Nissen fundoplication had a higher incidence of dysphagia, but the Toupet repair controlled the reflux equally or insignificantly better than the Nissen repair. The patients’ preexisting motility impairments did not correlate with the postoperative complaints, so the authors declared that tailoring antireflux procedures according to esophageal motility is not indicated. Wykypiel et al. [24] confirmed the equal efficiency of reflux control of Toupet compared with

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Nissen, besides restoring the preoperatively impaired bolus propagation after the Toupet procedure. Both groups of researchers [9, 24] found the Toupet procedure to be the better one, with fewer side effects.

Why We Should Adapt the Surgical Technique to the Individual Patient

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1. Most patients with large paraesophageal hernias are elderly. For many years, patients may stay asymptomatic. Historically, treatment was open surgical management of a large diaphragmatic defect too invasive for an older, minimally symptomatic patient who frequently already had other comorbidities. Because of rare but well-known and possibly life-threatening complications [25], we continued to offer these patients a »prophylactic operation« with a mortality of 0–5.4%. According to Stylopoulos et al. [26], the probability of needing emergency surgery is only 1.16% in the asymptomatic group. Therefore, only symptomatic or progressively symptomatic older patients should undergo elective surgery. 2. The incidence of failure of laparoscopic simple-sutured hiatal repair in patients with PEH is known to be quite high. Especially in series with systematic follow-up and consequent barium swallow examination, the recurrence rate ranges from 0% to 42% [4]. Nevertheless, the majority of patients are symptomatically improved and do not require interventions, just observation [27]. White et al. [27] conducted a 10-year follow-up of 31 patients who had had laparoscopic repair of PEH. They found that heartburn had improved from 54% to 12%, chest pain from 36% to 9%, dysphagia from 30% to 3%, and regurgitation from 50% to 6%, despite the recurrence rate of 32%. Only a small group needed reoperation. 3. The failure rate after fundoplication for reflux disease after 5-year follow-up is 10–15% [28]. The most common failure pattern is intrathoracic herniation of the intact wrap (61–84%) due to disruption of the crural repair [5, 6, 29]. The reoperation rate of around 10% dem-

onstrates the necessity to technically improve the durability of the cruroplasty. 4. Among the factors related to hiatal hernia recurrence are technical reasons, anatomic reasons (different hernia types I–IV, size of the hiatus, condition of the crura), and patientrelated reasons, including obesity, chronic obstructive pulmonary disease, constipation, weight lifting, age, vomiting in the early postoperative course, early physical activity, and so on. Patients with these predisposing factors should probably be primarily offered a meshreinforced crural repair. 5. Mesh decreases the risk of recurrence in hiatal repair [2, 17–19, 30, 31], but it carries the risk of mesh-related complications. These are very rare but may have disastrous consequences. To eliminate this small but serious risk, several surgeons promote the use of biomeshes, namely porcine small intestine submucosa [23]. Johnson et al. [2] reviewed the available literature and identified 19 studies reporting on the use of mesh in hiatal repair (PEH, laparoscopic fundoplication for reflux, or both). There were 729 sutured repairs and 639 mesh repairs with or without crura closure. After 20 months, there were fewer recurrences in the mesh group: 1.8% vs. 10.7%. No erosion was reported in this study or in series published by Frantzides et al. [18], Basso et al. [19], Gryska and Vernon [30], Granderath et al. [31], and Champion and Rock [17]. The awareness of potential mesh-related late sequelae in the dynamic hiatal area is certainly important. Nevertheless, by respecting the individual patient’s failure-risk profile, there must be a place for primary mesh-reinforced crural repair rather than waiting for a failure and then using the mesh in a technically demanding redo repair later on. The lightweight, megaporous, and oligofilament meshes have demonstrated less chronic inflammatory reaction and limited shrinkage in inguinal hernia repair. With this prosthetic material there is a justified expectation of good performance and low risk in hiatal repair as well, but long-term results are still lacking.

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⊡ Fig. 67.1. Small hiatal surface area

⊡ Fig. 67.3. Large hiatal surface area

⊡ Fig. 67.2. Low tension on the suture line

⊡ Fig. 67.4. Higher risk of crural repair failure

6. The risk of failure of the crural repair is predominantly determined by the size of the hiatus and the condition of the crura [32]. Measuring the hiatal surface area gives a rational background for a tailored concept of hiatal closure (⊡ Figs. 67.1–67.4).

▬ The recurrence risk depends strongly on the size of the hiatus and the condition of the crura. This justifies the simple sutured repair in patients with small hiatal defects and meshreinforced suture repair in patients with bigger defects, weak crura, and/or additional elevated risk factors. ▬ The traditional validation of Nissen vs. Toupet wrap must be scrutinized or reconfirmed [9, 24, 33–35]. ▬ The individualized approach to hiatal hernia repair (tailored repair [32]) must reflect the risk–benefit ratio of each individual patient, based on the available evidence from longterm follow-up if possible.

Conclusions ▬ Solidity and durability of crural repair are key, both for antireflux procedures as well as for PEH repair. ▬ Patients with increased recurrence risk should probably be offered a primary mesh-reinforced repair.

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References

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1. Draaisma WA, Gooszen HG, Tournoij E, Broeders IAMJ (2005) Controversies in paraesophageal hernia repair. Surg Endosc 19:1300–1308 2. Johnson JM, Carbonell AM, Carmody BJ, Jamal MK, Maher JW, Kellum JM, De Maria EJ (2006) Laparoscopic mesh hiatoplasty for paraesophageal hernias and fundoplications. Surg Endosc 20:362–366 3. Targarona EM, Bendahan G, Balague C, Garriga J, Trias M (2004) Mesh in the hiatus–a controversial issue. Arch Surg 139:1286–1296 4. Hashemi M, Peters JH, DeMeester TR, Huprich JE, Quek M, Hagen JA, Crookes PF, Theisen J, DeMeester SR, Sillin LF, Bremmer CG (2000) Laparoscopic repair of large type III hiatal hernia: objective follow-up reveals high recurrence rate. J Am Coll Surg 190:553–560 5. Hunter JG, Smith CD, Branum GD (1999) Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision. Ann Surg 230:595–604 6. Carlson MA, Frantzides CT (2001) Complications and results of primary minimally invasive antireflux procedures: a review of 10,735 reported cases. J Am Coll Surg 193:428–439 7. Nissen R (1956) A simple operation for control of reflux esophagitis. Schweiz Med Wochenschr 86:590–592 8. Toupet A (1963) Technique of esophago-gastroplasty with phrenogastropexy used in radical treatment of hiatal hernias as a supplement to Heller’s operation in cardiospasms. Mem Acad Chir (Paris) 89:384–389 9. Strate U, Emmermann A, Fibbe C, Layer P, Zornig C (2008) Laparoscopic fundoplication: Nissen versus Toupet twoyear outcome of a prospective randomized study of 200 patients regarding preoperative esophageal motility. Surg Endosc 22:21–30 10. Kuster GG, Gilroy S (1993) Laparoscopic technique for repair of paraesophageal hiatal hernias. J Laparoendosc Surg 3:331–338 11. Carlson MA, Condon RE, Ludwig KA, Schulte WJ (1998) Management of intrathoracic stomach with polypropylene mesh prosthesis reinforcement transabdominal hiatus hernia repair. J Am Coll Surg 187:227–230 12. Trus TL, Bax T, Richardson WS, Branum GD, Mauren SJ, Swanson LL, Hunter JG (1997) Complications of laparoscopic paraesophageal hernia repair. J Gastrointest Surg 1:221–228 13. Coluccio G, Ponzio S, Ambu V, Tramontano R, Cuomo G (2000) Dislocation into cardiac lumen of a PTFE prosthetic used in the treatment of voluminous hiatal sliding hernia, a case report. Minerva Chir 55:341–345 14. Zilberstein B, Ashkenasy R, Pajecki D, Granja C, Brito ACG (2005) Laparoscopic mesh repair antireflux surgery for treatment of large hiatal hernia. Dis Esophagus 18:166–169 15. Filipi CJ (2000) Laparoscopic hiatal hernia repair: why they fail. Hernia 4:219–222 16. Champion JK, McKernan JB (1998) Hiatal size and risk of recurrence after laparoscopic fundoplication [abstract]. Surg Endosc 12:565–570

17. Champion JK, Rock D (2003) Laparoscopic mesh cruroplasty for large paraesophageal hernias. Surg Endosc 17: 551–553 18. Frantzides C, Madan A, Carlson M, Stavropoulos G (2002) A prospective, randomized trial of laparoscopic polytetrafluoroethylene (PTFE) patch repair vs simple cruroplasty for large hiatal hernia. Arch Surg 137:649–652 19. Basso N, DeLeo A, Genco A, Rosato P, Rea S, Spaziani E, Privaera A (2000) 360° laparoscopic fundoplication with tension-free hiatoplasty in the treatment of symptomatic gastroesophageal reflux disease. Surg Endosc 14:164– 169 20. Granderath FA, Carlson MA, Champion JK, Szold A, Basso N, Pointner R, Frantzides CT (2006) Prosthetic closure of the esophageal hiatus in large hiatal hernia repair and laparoscopic antireflux surgery. Surg Endosc 20:367– 379 21. Dally E, Falk GL (2004) Teflon pledget reinforced fundoplication causes symptomatic gastric and esophageal luminal penetration Am J Surg 187:226–229 22. Balladas HG, Smith GS, Richardson MA, Dempsey ME, Falk GL (2000) Esophagogastric fistula secondary to Teflon pledget: a rare complication following laparoscopic fundoplication. Dis Esophagus 13:72–74 23. Oelschlager BK, Barreca M, Chang L, Pellegrini CA (2003) The use of small intestine submucosa in repair of paraesophageal hernias: initial observations of a new technique. Am J Surg 186:4–8 24. Wykypiel H, Hugl B, Gadenstaetter M, Bonatti H, Bodner J, Wetscher WJ (2008) Laparoscopic partial posterior (Toupet) fundoplication improves esophageal bolus propagation on scintigraphy. Surg Endosc 22:1845–1851 25. Skinner DB, Belsey RH (1967) Surgical management of esophageal reflux and hiatus hernia. Long-term results with 1030 patients. J Thorac Cardiovasc Surg 53:33–54 26. Stylopoulos N, Gazelle GS, Rattner DW (2002) Paraesophageal hernias: operation or observation? Ann Surg 236:492–500 27. White BC, Jeansonne LO, Morgenthal CB, et al. (2008) Do recurrences after paraesophageal repair matter? Surg Endosc 22:1107–1111 28. Franzén T, Anderberg B, Wirén M, Johansson KE (2005) Long-term outcome is worse after laparoscopic than after conventional Nissen fundoplication. Scand J Gastroenterol 40:1261–1268 29. Cadiere GB, Bruyns J, Himpens J, Vertruyen M (1996) Intrathoracic migration of the wrap after laparoscopic Nissen fundoplication. Surg Endosc 10:187 (S43) 30. Gryska PV, Vernon JK (2005) Tension-free repair of hiatal hernia during laparoscopic fundoplication: a ten-year experience. Hernia 9:150–155 31. Granderath F, Kamolz T, Schweiger M, Pasiut M, Haas C, Wykypiel H, Pointer R (2002) Long-term results of laparoscopic antireflux surgery. Surg Endosc 16:753–757 32. Granderath FA, Schweiger UM, Pointner R (2007) Laparoscopic antireflux surgery: tailoring the hiatal closure to the size of hiatal surface area. Surg Endosc 21:542–548

519 Chapter 67 · Strategy To Improve the Results? In Support of Individualized Procedures

33. Spechler SJ, Lee E, Ahnen D, Goyal R, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic Z, Young R, Williford W (2001) Long term outcome of medical and surgical therapies for gastroesophageal reflux disease. J Am Med Assoc 285:2331–2338 34. Kamolz T, Granderath FA, Bammer T, Pasiut M, Pointner R (2002) Dysphagia and quality of life after laparoscopic Nissen fundoplication in patients with and without prosthetic reinforcement of the hiatal crura. Surg Endosc 16:572–577 35. Hunter JG, Swanstrom L, Waring JP (1996) Dysphagia after laparoscopic antireflux surgery. The impact of operative technique. Ann Surg 224:51–57

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68

Questionnaire

522

Chapter 68 · Questionnaire

1. How many hernias do you perform each year? ▬ Inguinal ▬ Incisional ▬ Hiatal

A. Do you believe that infertility (due to obstructive azoospermia or ischaemic orchitis) is a potential complication of inguinal hernia repair? ▬ Yes 85% ▬ No 15%

6,175 1,935 486

2. Percentage of Operations Performed (%)

68

▬ Inguinal – Lichtenstein – Shouldice – TAPP – TEP – TIPP-Rives – Stoppa – Wantz – Plug/PHS – Others ▬ Hiatal – With mesh – Without mesh ▬ Incisional – Sublay – Onlay – Inlay – IPOM – Others

4. Spermatic Cord

B. Do you believe that the type of repair (mesh vs. nonmesh) has an impact on the integrity of the vas deferens and testicular function? ▬ Yes 62% ▬ No 38%

35% 13% 14% 25% <1% <1% <1% 8% 3%

C. Do you believe that the type of the mesh used (small porous mesh vs. large porous mesh) has an impact on the integrity of the vas deferens and testicular function? ▬ Yes 56% ▬ No 44%

20% 80%

D. Is potential alteration of the spermatic cord a reason to tailor your approach in inguinal hernia repair (i.e. young men, single testicle)? ▬ Yes 74% ▬ No 26%

51% 3% 4% 40% 2%

5. Infection 3. Type of Mesh Actually Used Inguinal

Incisional

Hiatal

Polypropylene (i.e. Atrium, Marlex)

35%

21%

Large porous polypropylene (i.e. UltraPro)

48%

33%

37%

Polyester (i.e. Mersilene)

10%

7%

0

ePTFE (i.e. DualMesh)

5%

24%

8%

Biological mesh (i.e. Surgisis)

0

10%

42%

Others

2%

5%

13%

0

A. Do you use single-shot antibiotic prophylaxis in hernia surgery to prevent infections? Inguinal hernia

Incisional hernia

Hiatal hernia

Yes

70%

Yes

92%

Yes

60%

No

30%

No

8%

No

40%

B. Do you believe that the kind of mesh materials (structure, polymer, kind of filament, pore size) has an impact on infection rate? ▬ Yes 69% ▬ No 31%

68

523 Chapter 68 · Questionnaire

C. Do you implant permanent mesh materials (no biological meshes) in potentially contaminated fields? Hernia repair for incarcerated inguinal/ incisional hernias ▬ Yes 90% ▬ No 10%

C. Should a suspected injured nerve be saved or resected? ▬ Saved 4% ▬ Resected 96% D. How do you resect a nerve? How?

Hernia repair + elective cholecystectomy ▬ Yes 77% ▬ No 23% Hernia repair + iatrogenic small bowel enterostomy ▬ Yes 56% ▬ No 44% Hernia repair + iatrogenic large bowel enterostomy ▬ Yes 21% ▬ No 79% D. Do you think there is a place for an antibioticsupplemented mesh in hernia repair to prevent/treat infections? In clean cases

In contaminated cases

In infected cases

Yes

26%

Yes

70%

Yes

50%

No

74%

No

30%

No

50%

6. Chronic Pain A. Do you believe that patient-related factors (i.e. age, gender, body mass index) are of major importance for the development of postoperative neuropathic pain? ▬ Yes 74% ▬ No 26% B. Do you believe that optimised (i.e. larger pores, monofilaments) mesh materials are able to decrease the overall amount of postoperative neuropathic pain? ▬ Yes 78% ▬ No 22%

Ligate the end?

Place end in muscle?

Scissor

79%

Yes

33%

Yes

52%

Knife

7%

No

67%

No

48%

Cautery

14%

E. Do you try to identify all three nerves during open inguinal hernia repair? ▬ Yes 40% ▬ No 60%

7. Adhesion/Migration/Erosion A. Do you believe in adhesions as a chronic inflammatory process? ▬ Yes 85% ▬ No 15% B. Which factors are responsible for the development of adhesions? ▬ Surgical technique (peritoneal damage) 100% ▬ Kind of mesh material 96% ▬ Kind of fixation 93% ▬ Patient’s individual response 86% C. Which factors determine the adhesive potency of a mesh material (multiple answers possible)? ▬ Polymer 79% ▬ Pore size 93% ▬ Kind of filaments (mono vs. multi) 79% ▬ Kind of antiadhesive barrier 89% D. Have you ever seen complications following hiatal hernia repair using a mesh material? ▬ Yes 52% ▬ No 48%

524

Chapter 68 · Questionnaire

E. Is there a need for further mesh optimisation for placement in the hiatal region? ▬ Yes 95% ▬ No 5%

68

Subject Index

A Abdominal colposuspension 440 Abdominal stiffness 223 Abdominal wall compliance 347 Abdominal wall surface 144 Abdominopelvic pain 306 Acute inflammatory response 366 Acute laparotomy wound failure 402 Adhesion 345, 354, 346, 378, 385, 446 Afferent nociceptors 172 Allodynia 170, 180 Amnion-derived cells 402 Amniotic cell therapy 405 Antiadhesive barrier 348 Antibiotic prophylaxis 126 Antireflux procedure 504 Anxiety 164 Arcuate line 488 Aß-fiber 210 Augmentation 228 Autologous skin 498 Axon 178 Axonotmesis 178 Aδ-fiber 210

B Bacterial colonization 395 Bacterial contamination 120 Bacterial resistance 126, 132 Band disconnection 430 Band erosion 430, 432 Band migration 432, 434, 435 Bariatric surgery 435 Bassini 464, 468 Bcl-2 (oncoprotein) 45 Bioacoustic effect 122 Biocompatibility 377 Biofilm 121 Biological tissue grafts 318 B-lymphocytes 306 Bridging 223, 228 Bulging 147

C Catecholamine-O-methyltransferase (COMT) 194 ß-catenin 306, 309, 311 Cefazolin 138

Cellular infiltration 108 Central nervous plasticity 181 Central neuroinflammation 171 C-fibers 210 Chemical barriers 357 Chronic groin sepsis 114, 116 Chronic inguinal pain 293 Chronic inguinodynia 290 Chronic pain 221, 222, 246, 257, 258, 266, 280, 294 Classification 120, 229, 494 C-myc 306, 309, 311 Collagen 172 Collagen coating 282, 389 Collagen deposition 368 Color doppler ultrasound (CDUS) 5 Complex regional pain syndromes (CRPS) 170, 208 Component separation technique 143 Composite biomaterials 356, 394 Condensed PTFE (cPTFE) 355 Contaminated environment 144 Contaminated surgical field 104 Contamination 116 Cooper’s ligament 488 COX-2 309 Crural repair 517

526

Subject Index

Cyclooxygenase-2 306, 311 Cytokine growth factors 402

D Deep infections 116 Degeneration 170 Depression 164, 195 Discomfort 223, 246 Double-crown technique 453 Drains 132 DualMesh 382, 397 DynaMesh IPOM 382 Dysejaculation 192 Dysesthesia 210 Dyspareunia 442 Dysphagia 511

E Early infections 80 Early wound failure 407 Effective porosity 378 Elasticity 236 Encapsulation 346 Enterotomy 335, 338 Entrapment 178, 180, 266, 294 Epineural fibrosis 179 Epineurectomy 179 Epineurium 178 Epineurotomy 179 ePTFE 44, 324, 356, 376, 382, 394 398 Erosion 434, 440, 442, 458 European guidelines 201, 476 Evidence-based medicine 480 Extensive scar tissue 223

F Fascicles 178 Fatty triangle 490

Fibrin glue 357 Fibroblastic response 270 Fibroblasts 172, 311, 367 Fibrocollagenous ingrowth 378 Fistula formation 120, 121, 458 Fixation 165, 258 Flap 499 Follicle-stimulating hormone (FSH) 58 Foreign body reaction 215, 423 Foreign body response 259 Foreign body sensation 276 Francis Usher 369 Fundoplication 506

G Gastric banding 430 Gastric fundus 507 Gastric herniation 414 Gastroesophageal junction 506 Gastroesophageal reflux disease (GERD) 504 Gastroplasty 508 Genetic factors 166 Genetic polymorphisms 194 Genetic variation 161 Genitofemoral nerves 178, 240 Genotype 194 Gentamicin 136 Global infection score (GIS) 482 Guidelines 478 Guillain-Barré syndrome 193

H Haematogenous spread 116 Hernia recurrence 109, 336, 394 Hiatal hernia repair 416 Hiatoplasty 425 Human acellular dermis (HADM) 104 Hyaluronic acid 388

Hyaluronic acid/carboxymethylcellulose (HA/CMC) membranes 357 Hyaluronidase cream 357 Hyperalgesia 170 Hyperexcitability 170 Hyperpathic pain 180

I Ideal mesh 373 Iliohypogastric nerve 178, 240, 289 Ilioinguinal nerve 178, 240 Impaired quality of collagen matrix synthesis 402 Improved laparotomy wound repair 405 Incisional hernia 221, 325, 332, 402, 486 – Formation 407 – Model 403 – Repair 376 Individualized therapy 170 Indocyanine green (ICG) 31 Infection 87, 126 – of a prosthetic material 395 – Rate 447 Infertility 306 Inflammation 121 Inflammatory – Cells 186, 367 – Pain 170 – Reaction 116, 441 – Response 223, 394, 446 Ingrowth maturation process 368 Inguinal Pain Questionnaire (IPQ) 194 Inguinodynia 287 Interfascicular neurolysis 179 International Association for the Study of Pain (IASP) 209 Intragastric band migration 430 Intraneural blood flow 188 Intraperitoneal onlay mesh (IPOM) 82, 376, 446, 494

527 Subject Index

IPOM 324 – Rabbit model 377

J Johnsen Score 23

K Keyhole technique 455 Ki67 23, 368, 383 Kugel repair 465

L Laparoscopic fundoplication 414 Laparoscopic hiatal hernia repair 504 Laparoscopic ventral hernia repair 82, 332, 366 Laparotomy wound breaking strength 403 LAPSIS trial 497 Large-pore mesh 186, 376 Late infections 80 Learning curve 465 Lichtenstein 5, 14, 23, 52, 126, 252, 464, 469 Lightweight mesh 276, 376 Lightweight polypropylene/ carboxymethylcellulose 371 Linea alba 402 Local anaesthesia 165 Luteinizing hormone (LH) 58

M Macrophages 306, 309, 311, 383, 396 Marlex 22, 30, 377

Mayo technique 497 Mesh attachment 223 Mesh bowel intrusion 120 Mesh bridging 495 Mesh contraction 345, 346, 348 Mesh cruroplasty 504, 510 Mesh explantation 293 Mesh infection 79, 119, 120, 336, 338, 447 Mesh inguinodynia 266 Mesh migration 423, 425, 458 Mesh-related infections 98 Mesh removal 115, 166, 296 Mesh shrinkage 424 Mesh surface 378, 386 Mesh surgery in urogynecology 440 Microneurolysis 179 Midline tension 223 Monocytes 383 Monofilament polypropylene (PP) 98 Mononuclear round cells 311 MycroMesh (MM) 395, 397 Myelin degeneration 258

N National database 476 Nerve damage 148 Nerve division 243 Nerve identification 239 Nerve injury 165 Nerve roots 178 Nerve trauma 156 Neuralgia 253 Neurapraxia 178 Neurectomy 166, 170, 241, 293, 294, 296 Neurofibromatosis 193 Neuroma 178 Neuroma pain 180 Neuromodulation 178, 182 Neuropathic-Pain 166, 170, 269, 288, 294, 466 Neurotmesis 178

Neurotomy 181 Nissen Fundoplication 422, 515 Nitric oxide (NO) 58 Nociceptive stimulus 164, 170 Nociceptive system 164 Nonsteroidal anti-inflammatory drugs 165 Notch-3 306, 309

O Obstructive azoospermia 51 Onlay techniques 82, 222 Open onlay mesh 494 Orchialgia 240, 287 Orchitis 253 Overlap 356

P Pain 166, 233, 252, 276 Pain level 236 Pain transmission 156 Pampiniform plexus 73 Paraesophageal hernia 414, 422, 504, 514 Paraesthesia 223 Parastomal hernia 325, 446, 447, 452 Parietene composite 382 Parietex composite 382 Pathological regeneration 170 Patient safety in surgery 481 PCNA reaction 46 PDS (polydioxanone) 388 Peak systolic velocity (PSV) 5 Pelvic organ prolapse 440 Perfusion-related fluorescence intensity (IC-CALC) 31 Perineurium 179 Peripheral surgical trauma 156 Peritoneal adhesions 306 Phenotype 194 Physical barriers 357

528

Subject Index

Physical fitness 195 Physical impairment 195 Physiotherapy 195 Planimetric analysis 386 Plug repair 301 Polyester 44 Polyglactin 910 mesh (PGM) 356 Polyneuropathy 170 Polypropylene 44, 126, 280, 355, 367, 377, 446 Polypropylene/expanded polytetrafluoroethylene (ePTFE) 367 Polypropylene mesh (PPM) , 355 Polytetrafluoroethylene 446 Polyvinylidene fluoride (PVDF) 22, 376, 382, 446 Pore size 223, 369, 376 Porosity 369 Postherniorrhaphy groin pain 164, 204, 279 Postherniorrhaphy inguinodynia 240 Postimplantation biomechanical strength 398 Postoperative pain 234, 336 Postoperative sensory dysfunctions 165 Pouch dilatation 430 Predictors of complications 252 Preoperative investigation 504 Preoperative pneumoperitoneum 486, 498 Prevention 136 Proceed 382 Prognostic factors 229 Prolene 14, 44 Proliferating cell nuclear antigen 45 Prophylactic antibiotics 84, 116 Prophylactic neurectomy 242 Prostheses 161 Prosthetic infection 497 Prosthetic mesh 486, 511 Prosthetic mesh infection 109 Prosthetic reinforcement 417 Pseudoneuroma 178 Psychosocial factors 194 PVDF 324

Q Quality of life 258 Questionnaire 229

R Randomized controlled trial (RCT) 468 Reactivation 195 Real-time adhesion formation 354 Recurrence rate 442, 452, 486 Recurrence rates after parastomal hernia mesh repair 452 Reflex sympathetic dystrophy 208 Rehabilitation 195 Reherniation 149 Retroesophageal window 506 Retromuscular space 490 Retroperitoneal triple neurectomy 300 Revascularization 108 Risk factor 164, 494 Rives 486

S Sandwich technique 455 Scar plate 350 – Formation 224 Scar retraction 417 Scar tissue 270 Schwann cells 172 Self-assessment (SA) levels 156 Seroma 336 – Formation 98 Sexual dysfunction 192 SF-36 questionnaire 280 Shouldice 30, 464, 469 Shrinkage 383, 387, 441, 458 Single-peptide wound therapy 407 Skin necrosis 146, 147

Sliding hernia 504 Sling procedure 440 Slippage 430, 507 Slipped nissen phenomenon 414 Small bowel obstruction 306 Small-pore meshes 186 Soft Tissue Patch (STP) 394, 397, 398 Sonographic resistive index (RI) 4 Spermatic cord 30, 270 Spermatogenesis 31 Spinal ganglion 181 Spiral tacks 234, 354 Standardisation 476 Standard procedure 472 Staphylococcus aureus 115, 136 Stem-cell-like multipotent cells express 402 Stem cells 401, 402 3D stereography 347 s-testosterone 15 Stoppa 464 Stress urinary incontinence 440 sublay technique 222 Suburethral sling 440 Sudeck’s atrophy 208 Superficial infections 114 Surgical site infection (SSI) 98, 114, 106 Surgical strategy 499 Surgical trauma 161 Suture cruroplasty 504 Suture pull-out force 284 Suture repair 228 Sweat secretion test 218 Swedish Hernia Register (SHR) 201

T Tailored approach 299, 472, 483, 494 Tailored concept 81 TAPP 203, 480 Targeted 170 Technical failure 471

529 Subject Index

Tensile strength 397 Tensiometric measurements 404 TEP 5, 201, 203, 480 Testicular atrophy 4, 5 Testicular torsion 7 TGF-β 405 Thermography 24 TiMesh Light 382 Tissue incorporation 398 Tissue ingrowth 345, 346, 365, 376 Tissue–prosthesis overlap 339 Tissue response 394 Titanium-coated meshes 383 T-lymphocytes 306, 309, 311, 383 Toupet 514, 515 Toxicity 138 Trabucco 52 Triple neurectomy 181, 288 TUNEL 59 – Histochemistry 23

V Vacuum-assisted closure (VAC) therapy 122, 326 VAS 280 Vasography 14, 23 Von Willebrand factor 45, 46 Vypro II 14, 44

W Wallerian degeneration 179, 215 Wantz 464 Watchful waiting 480 Wound breaking strength 405 Wound complication 336, 338 Wound infection 109, 136 – Rates 336 Wound oxygen levels 89 Wound tissue oxygenation 89 Wrap herniation 414, 416