The ASCRS Textbook of Colon and Rectal Surgery [3rd ed. 2016] 9783319259703, 9783319259680, 3319259687, 3319259709

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Scott R. Steele Tracy L. Hull Thomas E. Read Theodore J. Saclarides Anthony J. Senagore Charles B. Whitlow Editors

The ASCRS Textbook of Colon and Rectal Surgery Third Edition

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The ASCRS Textbook of Colon and Rectal Surgery

The ASCRS Textbook of Colon and Rectal Surgery Third Edition

Editors

Scott R. Steele, MD Tracy L. Hull, MD Thomas E. Read, MD Theodore J. Saclarides, MD Anthony J. Senagore, MD Charles B. Whitlow, MD

Editors Scott R. Steele, M.D Chief, Division of Colorectal Surgery University Hospitals Case Medical Center Professor of Surgery Case Western Reserve University Cleveland, OH, USA Thomas E. Read, MD Professor of Surgery Tufts University School of Medicine Lahey Hospital & Medical Center Burlington, MA, USA Anthony J. Senagore, MD Professor, Chief of Gastrointestinal Surgery University of Texas Medical Branch at Galveston Galveston, TX, USA

Tracy L. Hull, MD Professor of Surgery Cleveland Clinic Cleveland, OH, USA Theodore J. Saclarides, MD Ambrose and Gladys Bowyer Professor of Surgery Loyola University Chicago, IL, USA Charles B. Whitlow, MD Chief, Colorectal Surgery Ochsner Medical Center New Orleans, LA, USA

Videos to this book can be accessed at http://link.springer.com/book/10.1007/978-3-319-25970-3 ISBN 978-3-319-25968-0    ISBN 978-3-319-25970-3 (eBook) DOI 10.1007/978-3-319-25970-3 Library of Congress Control Number: 2016936561 Springer Cham Heidelberg New York Dordrecht London © ASCRS (American Society of Colon and Rectal Surgeons) 2016, corrected publication 2018 This work is subject to copyright. All rights are reserved by the Publisher, 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 physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Jointly published with The American Society of Colon and Rectal Surgeons, Arlington Heights, IL, USA Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com)

Foreword

One given definition of the word textbook is “a book used as a standard work for the study of a particular subject.” Our collective goal for the third edition of the American Society of Colon and Rectal Surgeons’ ASCRS Textbook of Colon and Rectal Surgery was to make this volume the standard for the study of colon and rectal surgery, providing a valuable resource for surgeons and healthcare providers at all stages of their career caring for patients with colorectal disease. In line with previous editions, we aimed to build upon the collective experience and expertise from national and international experts in the field, providing a completely revamped, up-to-date tome covering the wide breadth of colorectal disease. In addition to providing all newly written chapters, we have reorganized the text around the “pillars” of colorectal disease: perioperative (including endoscopy), anorectal disease, benign disease (including inflammatory bowel disease), malignancy, pelvic floor disorders, and a “miscellaneous” section that covers aspects both inside and beyond the operating room that are pertinent to providers at every level. This restructuring coincides effectively with the ASCRS Online Education Portal (www.fascrs.org) and mirrors the configuration of the Society’s collection of educational and CME-accredited programs including CREST and CARSEP. In addition, each chapter contains several Key Concepts that succinctly depict the major learning objectives for individual sections and are in line with the Core Curriculum for Colon and Rectal Surgery provided by the Association of Program Directors in Colon and Rectal Surgery and the key topics used by the American Board of Colon and Rectal Surgery. In addition, we have expanded beyond the initial print-only edition to encompass a multimedia platform with the availability of an electronic version of the text along with online videos depicting procedures, tips and tricks, and complications—all easily accessible through desktops, tablets, and smartphones to accommodate the mobile healthcare world in which we live. While this textbook was originally conceived as a means of providing state of the art information to residents in training and fully trained surgeons, our hope, more than anything, is that this volume continues to support the mission of the American Society of Colon and Rectal Surgeons as the world’s most established authority on colon and rectal disease. We are honored to have been a part of this project and wish to thank the leaders of the ASCRS for their continued support of the textbook. We especially would like to recognize the editors of the first and second editions for having the vision and purpose to produce such high-quality, evidence-­ based texts that have made the ASCRS Textbook of Colon and Rectal Surgery the success and reference it remains today. Lastly, we would like to thank our Developmental Editor Elektra McDermott for her extraordinary efforts and thoroughness in overseeing and ensuring its timely completion, and each chapter author and coauthor(s) for their devotion to this task and to the mission of the ASCRS. Since inception, it has been our privilege and pleasure to work with this tremendous gathering of authors and editors, as their unique contributions have come together to make this textbook a reality. Cleveland, OH Cleveland, OH Burlington, MA Chicago, IL Galveston, TX New Orleans, LA

Scott R. Steele, MD Tracy Hull, MD Thomas Read, MD Theodore Saclarides, MD Anthony Senagore, MD Charles Whitlow, MD v

Preface

The field of Colon and Rectal Surgery has a long and respected tradition of patient service, knowledge expansion, and education. The American Society of Colon and Rectal Surgeons (ASCRS) is the premier professional organization of this specialty. The leaders of our Society (ASCRS) recognized that there were several textbooks in the field of Colorectal Surgery, but none of which could be deemed as truly representative of the collective objective views of the ASCRS. At the inaugural meeting of the senior and associate editors, prior to the 2007 publication of the ASCRS Textbook of Colon and Rectal Surgery 1st edition, the group made several fundamental decisions. One of those decisions was to have chapters extensively referenced, authoritatively written, appropriately illustrated, and as unbiased as possible. This very important latter point was strictly enforced by adherence by the chapter authors to ASCRS materials including the evidence-based ASCRS clinical practice guidelines, core subjects, presentations at our annual meeting, questions in the colon and rectal self-assessment program (CARSEP), and material otherwise presented through official society vehicles. In addition, first edition chapters were, in general, written by a “junior” and a “senior” coauthor. A second decision was a rotation schedule for the editors: two to three of the editors would rotate off after each e­ dition. This would provide wider participation and ensure that the text would represent the specialty as a whole and not a select group of individuals. The overwhelming success of the first edition led to the publication of a second edition in 2011. The second edition expanded upon the first edition, added new authors, supplemented a significant number of color plates, and increased the text itself from 810 to 946 pages. The vision provided by the leaders of our Society was certainly correct, as attested to by the tremendous interest in both editions of the ASCRS textbooks. We are proud that the standardized reference for evidence-based material in Colorectal Surgery is the work product of our Society members, owned by our Society, and has become a source of financial support to our Society. In addition, a corresponding manual (the ASCRS Manual of Colon and Rectal Surgery), designed more towards residents in training and physicians desiring a focused reference, has been released for each edition and has also been exceptionally popular. The continued rapid expansion of knowledge, in part attested by the increased number of pages in each subsequent edition, as well as the new technologies and new techniques has ensured the longevity of our work and has necessitated this third edition. We congratulate the current editors Drs. Scott Steele, Tracy Hull, Thomas Read, Anthony Senagore, Theodore Sacclarides, and Charles Whitlow on their tremendous accomplishment. We also thank all of the chapter authors and coauthors whose dedication, devotion, energy, and expertise have enabled the editors to produce this volume. The third edition has been reorganized and completely rewritten to reflect advances in our specialty and the evolution of our practice. In addition, the current grouping of topics serves as a framework for the ongoing educational efforts of the Society and certification process by the American Board of Colon and Rectal Surgery. New developments in the management of colorectal diseases and our colleagues’ continued search for answers have produced the need for this and future editions of the ASCRS Textbook

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Preface

of Colon and Rectal Surgery. We are gratified that this significant educational endeavor ­continues to flourish. We commend this work to every practitioner of colorectal surgery throughout the world and eagerly await reports of its success. New Orleans, LA Weston, FL

Dave Beck, MD Steven Wexner, MD

Contents

Foreword............................................................................................................................ v Preface................................................................................................................................ vii Contributors...................................................................................................................... xv

Volume 1 Part I  Perioperative/Endoscopy 1 Anatomy and Embryology of the Colon, Rectum, and Anus................................ 3 Joseph C. Carmichael and Steven Mills 2 Colonic Physiology.................................................................................................... 27 Joshua I.S. Bleier and Kirsten Bass Wilkins 3 Anal Physiology: The Physiology of Continence and Defecation......................... 37 Vitaliy Poylin and Thomas E. Cataldo 4 Endoscopy.................................................................................................................. 45 Kurt Davis and Michael A. Valente 5 Endoscopic Management of Polyps, Polypectomy, and Combined Endoscopic and Laparoscopic Surgery........................................ 79 Kelly A. Garrett and Sang W. Lee 6 Preoperative Assessment of Colorectal Patients..................................................... 93 Jennifer S. Davids and Justin A. Maykel 7 Optimizing Outcomes with Enhanced Recovery................................................... 107 Conor P. Delaney and Raul Martin Bosio 8 Postoperative Complications.................................................................................... 121 Andrew Russ and Gregory D. Kennedy 9 Anastomotic Construction........................................................................................ 141 Steven R. Hunt and Matthew L. Silviera 10

Anastomotic Complications.................................................................................. 161 Konstantin Umanskiy and Neil Hyman

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Part II  Anorectal Disease 11 Approach to Anal Pain............................................................................................. 175 Amir L. Bastawrous 12 Hemorrhoids.............................................................................................................. 183 Martin Luchtefeld and Rebecca E. Hoedema 13 Anal Fissure............................................................................................................... 205 Kim C. Lu and Daniel O. Herzig 14 Anorectal Abscess and Fistula................................................................................. 215 Bradley R. Davis and Kevin R. Kasten 15 Complex Anorectal Fistulas..................................................................................... 245 Giulio A. Santoro and Maher A. Abbas 16 Rectovaginal Fistula.................................................................................................. 275 Jamie A. Cannon 17 Pilonidal Disease and Hidradenitis Suppurativa................................................... 289 Eric K. Johnson 18 Dermatology and Pruritus Ani................................................................................ 309 Wolfgang B. Gaertner and Genevieve B. Melton 19 Sexually Transmitted Infections.............................................................................. 325 Cindy Kin and Mark Lane Welton 20 Anal Intraepithelial Neoplasia................................................................................. 343 Rocco Ricciardi Part III  Malignant Disease 21 Anal Cancer............................................................................................................... 357 Tushar Samdani and Garrett M. Nash 22 Presacral Tumors...................................................................................................... 373 John Migaly and Christopher R. Mantyh 23 Molecular Basis of Colorectal Cancer and Overview of Inherited Colorectal Cancer Syndromes.................................................................................................... 383 Matthew F. Kalady and Y. Nancy You 24 Colorectal Neoplasms: Screening and Surveillance After Polypectomy.............. 417 Evie H. Carchman and Charles P. Heise 25 Colon Cancer: Preoperative Evaluation and Staging............................................ 433 Cary B. Aarons and Najjia N. Mahmoud 26 The Surgical Management of Colon Cancer.......................................................... 443 Matthew G. Mutch 27 Rectal Cancer: Preoperative Evaluation and Staging........................................... 471 Jorge Marcet

Contents

Contents

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28 Rectal Cancer: Neoadjuvant Therapy.................................................................... 481 Andrea Cercek and Julio Garcia-Aguilar 29 Local Excision of Rectal Neoplasia.......................................................................... 495 Mark H. Whiteford 30 Rectal Cancer: Watch and Wait.............................................................................. 507 George J. Chang 31

Proctectomy............................................................................................................... 517 Emmanouil P. Pappou and Martin R. Weiser

32 Rectal Cancer Decision-Making.............................................................................. 535 W. Donald Buie and Anthony R. MacLean 33 Colorectal Cancer: Postoperative Adjuvant Therapy.......................................... 547 Stephen M. Sentovich and Marwan Fakih 34 Colorectal Cancer: Surveillance After Curative-Intent Therapy......................... 555 Scott E. Regenbogen and Karin M. Hardiman 35 Colorectal Cancer: Management of Local Recurrence......................................... 571 Eric J. Dozois and Dorin T. Colibaseanu 36 Colorectal Cancer: Management of Stage IV Disease........................................... 589 Glenn T. Ault and Kyle G. Cologne 37

Appendiceal Neoplasms............................................................................................ 617 Constantine P. Spanos and Andreas M. Kaiser

38 Carcinoids, GISTs, and Lymphomas of Colon and Rectum................................. 631 David J. Maron

Volume 2 Part IV  Benign Colorectal Disease 39

Diverticular Disease.................................................................................................. 645 Jason Hall

40 Large Bowel Obstruction......................................................................................... 669 Karim Alavi and Charles M. Friel 41 Lower Gastrointestinal Hemorrhage...................................................................... 697 Brian R. Kann and H. David Vargas 42

Endometriosis............................................................................................................ 717 Michael J. Snyder

43 Trauma of the Colon, Rectum, and Anus............................................................... 735 W. Brian Perry

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Contents

44 Inflammatory Bowel Disease: Pathobiology........................................................... 749 Tara M. Connelly and Walter A. Koltun 45 IBD Diagnosis and Evaluation................................................................................. 771 Matthew M. Philp and Howard M. Ross 46 Medical Management of Chronic Ulcerative Colitis............................................. 787 Stefan D. Holubar and Mattias Soop 47 Medical Management of Crohn’s Disease............................................................... 807 Scott A. Strong 48 Anorectal Crohn’s Disease....................................................................................... 819 Stephen R. Gorfine 49 Crohn’s Disease: Surgical Management................................................................. 843 Roberta Muldoon and Alan J. Herline 50 Ulcerative Colitis – Surgical Management............................................................. 869 Mukta K. Krane, Erin O. Lange, and Alessandro Fichera 51 Complications of the Ileal Pouch............................................................................. 895 Daniel L. Feingold and P. Ravi Kiran 52 Infectious Colitides.................................................................................................... 911 Frederick R. Lane and Dipen C. Maun 53 Clostridium difficile Infection................................................................................... 929 David B. Stewart Sr. 54 Radiation, Microscopic, Ischemic Colitis................................................................ 951 Isabelle Raîche and Husein Moloo 55 Intestinal Stomas....................................................................................................... 971 Michael F. McGee and Peter A. Cataldo 56 Functional Complications After Colon and Rectal Surgery................................. 1015 Dana M. Hayden and Alex Jenny Ky Part V  Pelvic Floor Disorders 57 Common Tests for the Pelvic Floor.......................................................................... 1027 Dana R. Sands and Amy J. Thorsen 58 Evaluation of Constipation and Treatment of Abdominal Constipation............. 1051 Muneera R. Kapadia and Madhulika K. Varma 59

Obstructed Defecation.............................................................................................. 1063 M. Shane McNevin

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Rectal Prolapse.......................................................................................................... 1077 Brooke Gurland and Massarat Zutshi

61 Evaluation and Treatment of FI.............................................................................. 1091 Ian M. Paquette and Liliana Bordeianou

Contents

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62 Functional Bowel Disorders for the Colorectal Surgeon....................................... 1107 Jennifer M. Ayscue and Anjali S. Kumar 63 Middle and Anterior Compartment: Issues for the Colorectal Surgeon............. 1121 Cecile A. Unger and Marie Fidela R. Paraiso Part VI  Miscellaneous 64 Pediatric Colorectal Disorders................................................................................. 1137 Daniel H. Teitelbaum and Peter F. Ehrlich 65 Considerations for Geriatric Patients Undergoing Colorectal Surgery............... 1151 Kevin R. Kasten and Todd D. Francone 66 Health Care Economics............................................................................................ 1171 Guy R. Orangio 67 Ethical Issues in Colorectal Surgery....................................................................... 1189 Jason D. Keune 68 Welcome to Litigation............................................................................................... 1197 Dennis K. Ames 69

Surgical Education.................................................................................................... 1219 Bradley J. Champagne and Helen M. MacRae

70 Maintenance of Certification: Current Status and Future Considerations........ 1229 Jan Rakinic and W. Donald Buie 71 Quality and Safety in Colon and Rectal Surgery................................................... 1239 Elizabeth C. Wick and Jonathon Efron 72

Practice Management............................................................................................... 1259 Eric M. Haas

Correction.......................................................................................................................... E1 Index................................................................................................................................... 1273

The original version of this book was revised. A correction to this book can be found at https://doi.org/10.1007/978-3-319-25970-3_73

Contributors

Editors Tracy Hull, MD Department of Surgery, Cleveland Clinic, Cleveland, OH, USA

Thomas Read, MD Tufts University School of Medicine, Lahey Hospital & Medical Center, Burlington, MA, USA

Theodore Saclarides, MD Loyola University, Chicago, IL, USA Anthony Senagore, MD University of Texas Medical Branch at Galveston, Galveston, TX, USA

Scott R. Steele, MD Division of Colorectal Surgery, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA

Charles Whitlow, MD Colorectal Surgery, Ochsner Medical Center, New Orleans, LA, USA Authors

Cary B. Aarons, MD Division of Colon and Rectal Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

Maher A. Abbas, MD, FACS, FASCRS Digestive Disease Institute, Cleveland Clinic Abu Dhabi Hospital, Abu Dhabi, UAE

Karim Alavi, MD, MPH Colon and Rectal Surgery Fellowship Program, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA

Dennis K. Ames, JD La Follette, Johnson, Dehaas, Fesler, and Ames, Santa Ana, CA, USA

Glenn T. Ault, MD, MSEd Division of Colorectal Surgery, Department of Surgery, University of Southern California, Los Angeles, CA, USA

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Jennifer M. Ayscue, MD, FACS, FASCRS Section of Colon & Rectal Surgery, Department of Surgery, MedStar Washington Hospital Center, Washington, DC, USA

Amir L. Bastawrous, MD, MBA Swedish Colon and Rectal Clinic, Swedish Cancer Institute, Seattle, WA, USA

Joshua I.S. Bleier, MD, FACS, FASCRS Perelman School of Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA

Liliana Bordeianou, MD Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

Raul Martin Bosio, MD, MSBS Division of Colon and Rectal Surgery, Department of Surgery, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA

W. Donald Buie, MD, MSc, FRCSC, FACS Department of Surgery, Foothills Hospital, University of Calgary, Calgary, AB, Canada

Jamie Cannon, MD Division of Gastrointestinal Surgery, Department of Surgery, University of AlabamaBirmingham, Birmingham, AL, USA

Evie Carchman, MD Department of General Surgery, University of Wisconsin, Madison, WI, USA

Joseph C. Carmichael, MD Department of Surgery, University of California, Irvine, Irvine, CA, USA

Peter A. Cataldo, MD, FACS, FASCRS Department of Surgery, University of Vermont Medical Center, University of Vermont College of Medicine, Burlington, VT, USA

Thomas E. Cataldo, MD, FACS, FASCRS Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Andrea Cercek, MD Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Bradley J. Champagne, MD, FACS, FASCRS Department of Surgery, University Hospital Case Medical Center, Cleveland, OH, USA

George J Chang, MD, MS New Technologies in Oncologic Surgery Program, Department of Surgical Oncology, The University of MD Anderson Cancer Center, Houston, TX, USA

Dorin T. Colibaseanu, MD Department of General Surgery, Mayo Clinic, Rochester, MN, USA

Kyle G. Cologne, MD Division of Colorectal Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

Contributors

Contributors

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Tara M. Connelly, MD, MB, BCh, MSc Division of Colon and Rectal Surgery, Milton S. Hershey Medical Center, Hershey, PA, USA

Jennifer S. Davids, MD Department of Surgery, Division of Colon and Rectal Surgery, University of Massachusetts Memorial Medical Center, Worcester, MA, USA

Bradley R. Davis, MD, FACS, FASCRS Department of Surgery, Charlotte Hospitals Medical Center, Charlotte, NC, USA

Kurt Davis, MD Department of Surgery, William Beaumont Army Medical Center, El Paso, TX, USA

Conor P. Delaney, MD, MCh, PhD, FRCSI, FACS, FASCRS Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA

Eric J. Dozois, MD Department of Surgery, Mayo Clinic, Rochester, MN, USA

Jonathan Efron, MD Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, MD, USA

Peter F. Ehrlich, MD, MSc Section of Pediatric Surgery, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor, MI, USA

Marwan Fakih, MD Department of Medical Oncology and Therapeutic Diagnostics, City of Hope Medical Center, Duarte, CA, USA

Daniel Feingold, MD Columbia University, New York, NY, USA

Alessandro Fichera, MD, FACS, FASCRS Section of Gastrointestinal Surgery, Department of Surgery, University of Washington, Seattle, WA, USA

Todd D. Francone, MD, MPH Department of Colon and Rectal Surgery, Lahey Hospital & Medical Center, Tufts University Medical Center, Burlington, MA, USA

Charles M. Friel, MD Department of Surgery, University of Virginia Medical Center, Charlottesville, VA, USA

Wolfgang B. Gaertner, MSc, MD Department of Colon and Rectal Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA

Julio Garcia-Aguilar, MD, PhD Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Kelly A. Garrett, MD, FACS, FASCRS Section of Colon and Rectal Surgery, Department of General Surgery, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA

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Stephen R. Gorfine, MD Division of Colorectal Surgery, Department of Surgery, The Mount Sinai Hospital, New York, NY, USA

Brooke Gurland, MD Department of Colorectal Surgery, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

Eric M Haas, MD, FACS, FASCRS Division of Colon and Rectal Surgery, Houston Methodist Hospital, Houston, TX, USA; Minimally Invasive Colon and Rectal Surgery Fellowship, The University of Texas Medical School, Houston, TX, USA; Colorectal Surgical Associates, LLP LTD, Houston, TX, USA

Karin E. Hardiman, MD, PhD Division of Colorectal Surgery, University of Michigan, Ann Arbor, MI, USA

Dana M Hayden, MD, MPH Department of General Surgery, Loyola University Medical Center, Maywood, IL, USA

Charles P. Heise, MD, FACS, FASCRS Department of Surgery, University of WI School of Medicine and Public Health, Madison, WI, USA

Alan J. Herline, MD Department of Surgery, Georgia Regents University, Augusta, GA, USA

Daniel O. Herzig, MD, FACS, FASCRS Division of Gastroenterology and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR, USA

Rebecca E. Hoedema, MS, MD, FACS, FASCRS Department of Colon and Rectal Surgery, Spectrum Health/Ferguson Clinic, Grand Rapids, MI, USA

Stefan D. Holubar, MD, MS, FACS, FASCRS Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

Steven R. Hunt, MD Section of Colon and Rectal Surgery, Division of General Surgery, Barnes Jewish Hospital, St. Louis, MO, USA; Department of Surgery, Section of Colon and Rectal Surgery, Washington University School of Medicine, St. Louis, MO, USA

Neil Hyman, MD, FACS, FASCRS Section of Colon and Rectal Surgery, University of Chicago Medicine, Chicago, IL, USA

Eric K. Johnson, MD Uniformed Services University of the Health Sciences, Bethesda MD, USA; Department of Surgery, Madigan Army Medical Center, Joint Base Lewis-McChord, WA, USA

Andreas M. Kaiser, MD, FACS, FASCRS Keck Medical Center of the University of Southern California, Los Angeles, CA, USA Matthew F. Kalady, MD Comprehensive Colorectal Cancer Program, Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA

Contributors

Contributors

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Brian R. Kann, MD, FACS, FASCRS Department of Colon & Rectal Surgery, Ochsner Medical Center, New Orleans, LA, USA

Muneera R Kapadia, MD, MME Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA

Kevin R. Kasten, MD Department of Surgery, Vidant Medical Center, Brody School of Medicine at East Carolina University, Greenville, NC, USA

Gregory D. Kennedy, MD, PhD Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA

Jason D. Keune, MD, MBA Department of Surgery, St. Louis University School of Medicine, St. Louis, MO, USA

Cindy Kin, MD Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

P. Ravi Kiran, MBBS, MS (Gen Surgery), FRCS (Eng), FRCS (Glas), FACS, MSc (EBM) Oxford Center for Innovation and Outcomes Research, Columbia University Medical Center, New York, NY, USA; Mailman School of Public Health, New York, NY, USA; Division of Colorectal Surgery, Department of Colorectal Surgery, New York Presbyterian Hospital, New York, NY, USA

Walter A. Koltun, MD, FACS, FASCRS Department of Surgery, Division of Colon and Rectal Surgery, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA

Mukta Katdare Krane, MD, FACS Department of Surgery, University of Washington, Seattle, WA, USA

Anjali S. Kumar, MD, MPH, FACS, FASCRS Director, Colon & Rectal Surgery Program, Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA

Alex Jenny Ky, MD Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA

Frederick R. Lane, MD Kendrick Colon and Rectal Center, Franciscan St. Francis Health Indianapolis, Indianapolis, IN, USA

Erin O. Lange, MD, MSPH Department of Surgery, University of Washington Medical Center, Seattle, WA, USA

Sang W. Lee, MD, FACS, FASCRS Department of General Surgery, Section of Colon and Rectal Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Kim C. Lu, MD, FACS, FASCRS Division of Gastrointestinal and General Surgery, Department of Surgery, Oregon Health and Science University, Portland, OR, USA

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Martin Luchtefeld, MD, FACS, FASCRS Department of Colon and Rectal Surgery, Spectrum Health/Ferguson Clinic, Grand Rapids, MI, USA

Anthony R. MacLean, MD, FRCSC, FACS Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada Helen M. MacRae, MD, MA, FRCSC, FACS Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

Najjia N. Mahmoud, MD Division of Colon and Rectal Surgery, Department of Surgery, University of Philadelphia, Philadelphia, PA, USA

Christopher R. Mantyh, MD Department of Surgery, Duke University Medical Center, Durham, NC, USA

Jorge Marcet, MD Department of Surgery, Tampa General Hospital, Tampa, FL, USA

David J. Maron, MD, MBA Colorectal Surgery Residency Program, Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA

Dipen C. Maun, MD Kendrick Colon and Rectal Center, Franciscan St. Francis Health Indianapolis, Indianapolis, IN, USA

Justin A. Maykel, MD Division of Colon and Rectal Surgery, Department of Surgery, University of Massachusetts Memorial Medical Center, Worcester, MA, USA

Michael F. McGee, MD, FACS, FASCRS Division of Gastrointestinal and Oncologic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

M. Shane McNevin, MD, FASCRS Sacred Heart Hospital, Spokane, WA, USA

Genevieve B. Melton, MD, PhD Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA

John Migaly, MD, FACS, FASCRS Department of Surgery/Advanced Oncologic and GI Surgery, Duke University Hospital, Durham, NC, USA

Steven Mills, MD Department of Surgery, University of California, Irvine, Orange, CA, USA

Husein Moloo, MD, MSc, FRCS Department of Surgery, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada

Roberta Muldoon, MD Department of Surgery, Vanderbilt University Hospital, Nashville, TN, USA

Contributors

Contributors

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Matthew Mutch, MD, FACS, FASCRS Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

Garrett M. Nash, MD, MPH Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA Guy R. Orangio, MD, FACS, FASCRS Division of Colon and Rectal Surgery, Department of Surgery, University Hospital, Louisiana State University, New Orleans, LA, USA

Emmanouil P. Pappou, MD, PhD Department of Colorectal Surgery, Columbia University, New York, NY, USA

Ian M. Paquette, MD Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA Marie Fidela R. Paraiso, MD Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH, USA

W. Brian Perry, MD, FASCRS Audie L. Murphy VA Medical Center, San Antonio, TX, USA

Matthew M. Philp, MD, FACS, FASCRS Division of Colon and Rectal Surgery, Temple University Hospital, Philadelphia, PA, USA

Vitaly Y. Poylin, MD, FACS, FASCRS Division of Colon and Rectal Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Isabelle Raîche, MD, FRCS Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada Jan Rakinic, MD Section of Colorectal Surgery, Department of Surgery, Southern Illinois University, Springfield, IL, USA

Scott E. Regenbogen, MD, MPH Division of Colorectal Surgery, University of Michigan, Ann Arbor, MI, USA

Rocco Ricciardi, MD, MPH Lahey Hospital and Medical Center, Burlington, MA, USA

Howard M. Ross, MD Department of Surgery, Temple University Health System, Philadelphia, PA, USA

Andrew Russ, MD Department of Surgery, University Colon and Rectal Surgery, University of Tennessee Medical Center, Knoxville, TX, USA

Tushar Samdani, MD, MS, DNB(Surg) Department of Colorectal Surgery, Medstar Saint Mary’s Hospital, Leonardo Town, MD, USA

Dana R. Sands, MD, FACS, FASCRS Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL, USA

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Giulano A. Santoro, MD, PhD Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE

Stephen M. Sentovich, MD, MBA Department of Surgical Oncology, City of Hope, Duarte, CA, USA Matthew L. Silviera, MD Section of Colon and Rectal Surgery, Department of Surgery, Barnes Jewish Hospital, Washington University School of Medicine, St. Louis, MO, USA

Michael J. Snyder, MD, FACS Colon and Rectal Surgery Residency Program, The University of Texas Medical School at Houston, Houston, TX, USA; Department of Surgery, Houston Methodist TMC, Houston, TX, USA

Mattias Soop, MD, PhD Department of Surgery, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Center, The University of Manchester, Manchester, UK

Constantine P. Spanos, MD, FACS, FASCRS Department of Surgery, Aristotelian University of Thessaloniki, Panorama-Thessaloniki, Greece

David B. Stewart Sr. , MD, FACS, FASCRS Division of Colorectal Surgery, Department of Surgery, M. S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA, USA

Scott A. Strong, MD Division of GI and Oncologic Surgery, Northwestern Medicine, Chicago, IL, USA

Daniel Teitelbaum, MD Section of Pediatric Surgery, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, MI, USA

Amy J. Thorsen, MD Department of Colon and Rectal Surgery, University of Minnesota, Minneapolis, MN, USA

Konstantin Umanskiy, MD, FACS, FASCRS Section of Colon and Rectal Surgery, University of Chicago Medicine, Chicago, IL, USA

Cecile A. Unger, MD, MPH Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH, USA

Michael A. Valente, DO, FACS, FASCRS Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA

H. David Vargas, MD, FACS, FASCRS Department of Colon and Rectal Surgery, Ochsner Medical Center, New Orleans, LA, USA

Madhulika K. Varma, MD Division of Colon and Rectal Surgery, University of California-San Francisco, San Francisco, CA, USA

Contributors

Contributors

xxiii

Martin R Weiser, MD Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Mark Welton, MD, MHCM Department of Surgery, Stanford Health Care, Stanford, CA, USA

Elizabeth C. Wick, MD Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University, Baltimore, MD, USA Kirsten Bass Wilkins, MD, FACS, FASCRS UMDNJ Robert Wood Johnson University Hospital, Edison, NJ, USA

Y. Nancy You, MD, MHSc Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Massarat Zutshi, MD Department of Colorectal Surgery, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA

Part I Perioperative/Endoscopy

1 Anatomy and Embryology of the Colon, Rectum, and Anus Joseph C. Carmichael and Steven Mills

Key Concepts • The dentate line represents a true division between embryonic endoderm and ectoderm. • The location of the anterior peritoneal reflection is highly variable and can be significantly altered by disease such as rectal prolapse. • The right and left ischioanal space communicate posteriorly through the deep postanal space between the levator ani muscle and anococcygeal ligament. • The junction between the midgut (superior mesenteric artery) and the hindgut (inferior mesenteric artery) leads to a potential watershed area in the area of the splenic flexure. • There is a normal, three-stage process by which the intestinal tract rotates during development beginning with herniation of the midgut followed by return of the midgut to the abdominal cavity and ending with its fixation.

 natomy of the Anal Canal and Pelvic A Floor Textbooks of anatomy would define the “anatomic” anal canal as beginning at the dentate line and extending to the anal verge. This definition is one defined truly by the embryology and mucosal histology. However, the “surgical” anal canal, as first defined by Milligan and Morgan, [1] extends from the anorectal ring to the anal verge. The surgical definition of the anal canal takes in to account the surrounding musculature that is critical to consider during the conduct of operations from low anterior resection to anal fistulotomy. The surgical anal canal is formed by the internal anal sphincter, external anal sphincter, and puborectalis (Figure 1-1) and is easily identified on digital examination and ultrasound imaging. On average, the surgical anal canal is longer in males than in females. Intraoperative measurements of the posterior anal canal have estimated the surgical anal canal to

be 4.4 cm in men compared with 4.0 cm in women [2]. In addition, the anal canal was shown to be a unique muscular unit in that its length did not change with age. The anatomy of the anal canal has also been characterized using magnetic resonance imaging. MR imaging does not show a difference in the length of the posterior anal canal in men and women, but does show that the anterior and posterior external anal sphincter length (not including the puborectalis) is significantly shorter in women [3]. The anal canal forms proximally where the rectum passes through the pelvic hiatus and joins with the puborectalis muscle. Starting at this location, the muscular anal canal can be thought of as a “tube within a tube.” The inner tube is the visceral smooth muscle of the internal anal sphincter and longitudinal layer that is innervated by the autonomic nervous system. The outer muscular tube consists of somatic muscles including the components of the puborectalis and external anal sphincter [4]. It is the outer muscular tube that provides conscious control over continence and is strengthened during Kegal exercises. The external anal sphincter extends distal to the internal anal sphincter and the anal canal terminates at the anal verge where the superficial and sub­ cutaneous portions of the external anal sphincter join the dermis.

Anal Canal Epithelium The proximal anal canal has a pink appearance and is lined by the columnar epithelium of the rectal mucosa. Six to twelve millimeters proximal to the dentate line, the anal transition zone (ATZ) begins. The ATZ appears purple in color and represents an area of gradual transition of columnar epithelium to squamous epithelium. The columns of Morgagni are noted in this area were redundant columns of tissue are noted with anal crypts at their base. This forms the rippled dentate line (or pectinate line) which may be most easily identified by locating the anal crypts at the base of the Columns of Morgagni. Anal crypts are connected to

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_1

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J.C. Carmichael and S. Mills

Longitudinal muscle Circular muscle Valve of Houston Peritoneal reflection

Column of Morgagni

Conjoined longitudinal muscle

Iliococcygeus Pubococcygeus

Levator ani muscle

Puborectalis Internal anal sphincter muscle Dentate line

Anal crypt

External anal sphincter muscle

Anal gland Intersphincteric groove

Corrugator cutis ani muscle Anoderm

Anal verge

Figure 1-1.  Anal canal.

u­ nderlying anal glands which are the presumed source of sepsis in the majority of anorectal abscesses and fistula. On average, there are six anal glands surrounding the anal canal (range 3–12) [4–6] and they tend to be more concentrated in the posterior quadrants. More than one gland may open into the same crypt and some crypts may not be connected to anal glands. The anal gland ducts proceed inferior and lateral from the anal canal and enter the submucosa where two-­ thirds enter the internal anal sphincter and half terminate in the intersphincteric plane [5]. It is theorized that obstruction of these ducts leads to anal fistula and abscess [4]. Knowledge of the anatomy also explains why the internal opening of a “cryptoglandular” anal fistula should typically be at the dentate line. Distal to the dentate line, the anoderm begins and extends for approximately 1.5 cm. Anoderm has squamous histology and is devoid of hair, sebaceous glands, and sweat glands. At the anal verge, the anal canal lining becomes, thickened, pigmented and contains hair follicles—this represents ­normal skin. The dentate line represents a true division between embryonic endoderm and ectoderm. Proximal to the dentate line, the innervation is via the sympathetic and parasympathetic systems, with venous, arterial, and lymphatic drainage associated with the hypogastric vessels. Distal to the dentate line, the innervation is via somatic nerves with blood supply and drainage from the inferior hemorrhoidal system.

Internal Anal Sphincter The internal anal sphincter (IAS) is the downward continuation of the circular smooth muscle of the rectum and terminates with a rounded edge approximately 1 cm proximal to the distal aspect of the external anal sphincter. 3D imaging studies of this muscle demonstrate the overall volume does not vary according to gender, but the distribution is different with women tending to have a thicker medial/distal internal anal sphincter [7]. Overall, the IAS was found to be approximately 2 mm in thickness and 35 mm in length. The authors note that on any study, it is difficult to identify the proximal portion of the IAS as it is a continuation of the wall of the lower rectum.

Conjoined Longitudinal Muscle The anatomy and function of the perianal connective tissue is often overlooked, but plays a significant role in normal anorectal function. Measuring approximately 0.5–2.0 mm in thickness, the conjoined longitudinal muscle (or conjoined longitudinal coat) lies in between the internal and external anal sphincters. It begins at the anorectal ring as an extension of the longitudinal rectal muscle fibers and descends caudally joined by fibers of the puborectalis muscle [8]. At its most caudal aspect, some of the conjoined longitudinal ­muscle fibers (referred to as corrugator cutis ani muscle)

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

t­raverse the distal external anal sphincter and insert into the perianal skin and some enter the fat of the ischiorectal fossa. Fibers of the conjoined longitudinal muscle also pass obliquely and caudally through the internal anal sphincter to interlace in a network within the subepithelial space. These subepithelial smooth muscle fibers were originally described by Treitz in 1853 [9] and have been referred to as Treitz’s muscle. They have also been referred to corrugator cutis ani, musculus submucosae ani, mucosal suspensory ligament, and musculus canalis ani [10] It has been hypothesized by Thomson that disruption of Treitz’s muscles results in anal cushion prolapse, vascular outflow obstruction, and hemorrhoidal bleeding and thrombosis [11]. Haas and Fox have hypothesized that the conjoined longitudinal muscle, along with the network of connective tissue that it supports, plays a role in minimizing anal incontinence after sphincterotomy.

External Anal Sphincter The external anal sphincter (EAS) is composed of striated muscle that forms an elliptical tube around the internal anal sphincter and conjoined longitudinal muscle. As it extends beyond the distal most aspect of the internal anal sphincter the intersphincteric groove is formed. At its distal most aspect, corrugator cutis ani muscle fibers from the conjoined longitudinal muscle traverse the external anal sphincter and insert into the perianal skin. Milligan and Morgan described the external anal sphincter as having three distinct divisions from proximal to distal that were termed: sphincter ani externus profundus, superficialis, and subcutaneus [1]. With time, this theory of three distinct divisions was proven invalid by Goligher who demonstrated that the external anal sphincter was truly a continuous sheet of skeletal muscle extending up to the puborectalis and levator ani muscles [12]. While the external anal sphincter does not have three distinct anatomic layers, it is not uncommon to see the proximal portion of the EAS referred to as deep EAS, the mid-portion referred to as the superficial EAS and the most distal aspect as the subcutaneous EAS. The mid EAS has posterior attachment to the coccyx via the anococcygeal ligament and the proximal EAS becomes continuous with the puborectalis muscle. Anteriorly, the proximal EAS forms a portion of the perineal body with the transverse perineal muscle. There are clear differences in the morphology of the anterior external anal sphincter that have been demonstrated on both MRI and three dimensional endoanal ultrasound studies in normal male and female volunteers [13, 14]. The normal female external anal sphincter has a variable natural defect occurring along its proximal anterior length below the level of the puborectalis sling that was demonstrated in 75% of nulliparous volunteers. This defect correlated with findings on anal manometry and the authors noted that it can make interpretation of an isolated endoanal ultrasound difficult resulting in over-reporting of

obstetric sphincter defects [13]. This natural defect of the anterior anal sphincter provides some justification as to why anterior anal sphincterotomy is not routinely recommended in women. The external anal sphincter is innervated on each side by the inferior rectal branch of the pudendal nerve (S2 and S3) and by the perineal branch of S4. There is substantial overlap in the pudendal innervation of the external anal sphincter muscle on the two sides which enables re-innervation to be partially accomplished from the contralateral side following nerve injury [15].

Perineal Body The perineal body represents the intersection of the external anal sphincter, superficial transverse perinei, deep transverse perinei, and bulbospongiosus (also referred to as bulboca­ vernosus) muscles (Figure 1-2). Recent research, based on advanced magnetic resonance and ultrasound imaging, has suggested that the transverse perinei (TP) and bulbospongiosus (BS) muscles contribute significantly to anal continence [16]. It has been proposed that the EAS, TP and BS muscles be collectively referred to as the “EAS complex muscles.” In this theory, the EAS complex morphology is “purse string” shaped rather than the typical “donut” shape previously considered. When these muscles are considered as a functional unit, it lends further support to the idea that it is critical to attempt to repair the perineal body during overlapping sphincter reconstructions.

Pelvic Floor Muscles In addition to the anal sphincter and perineal body, the levator ani (LA) muscles contribute to pelvic organ support. For example, injury to the LA is seen in 55% of women with pelvic organ prolapse, but in only 16% without prolapse [17]. The LA has three subdivisions including the pubococcygeus (aka pubovisceral), puborectalis, and iliococcygeus. Some authors had previously suggested that the puborectalis was part of the deep portion of the EAS [18]; however, a significant amount of evidence has been presented to the contrary. In vivo MRI measurements in women have shown distinct, visible muscle fascicle directions for each of the three LA component muscles [19]. Embryology studies have also demonstrated that the puborectalis muscle is a portion of the LA muscle and shares a common primordium with the iliococcygeus and pubococcygeus muscles [20]. Innervation of the levator ani muscles has been described in detailed cadaveric studies [21]. The contemporary cadaveric studies suggest that the LA muscles are innervated by the pudendal nerve branches: perineal nerve and inferior ­rectal nerve as well as direct sacral nerves S3 and/or S4 (i.e., levator ani nerve) [22]. The pubococcygeus muscle and

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J.C. Carmichael and S. Mills

Female Pelvic Floor

Bulbospongiosus muscle Perineal body

Superficial transverse perinei muscle

Ischial tuberosity Iliococcygeus muscle Pubococcygeus muscle Puborectalis muscle

External anal sphincter

Gluteus maximus

Anococcygeal ligament Tip of coccyx

Male Pelvic Floor

Bulbospongiosus muscle Perineal body

Superficial transverse perinei muscle

Ischial tuberosity Iliococcygeus muscle Pubococcygeus muscle Puborectalis muscle

External anal sphincter

Gluteus maximus

Anococcygeal ligament Tip of coccyx

Figure 1-2.  Pelvic floor muscles.

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

Female Pelvic Floor

Superficial transverse perinei muscle

Perineal artery and vein Perineal nerve Internal pudendal artery and vein

Ischial tuberosity Pudendal nerve

Levator ani muscle

Inferior rectal artery

External anal sphincter

Inferior rectal nerve

Anococcygeal ligament Coccyx

Male Pelvic Floor

Perineal artery and vein

Superficial transverse perinei muscle

Perineal nerve

Ischial tuberosity

Internal pudendal artery and vein

Pudendal nerve

Levator ani muscle

Inferior rectal nerve

External anal sphincter

Inferior rectal artery

Anococcygeal ligament Coccyx

Figure 1-3.  Pelvic floor nerves and blood supply.

puborectalis muscle are primarily innervated by the ­pudendal nerve branches while the iliococcygeus muscle is primarily innervated by the direct sacral nerves S3 and/or S4 (Figure 1-3).

Puborectalis Muscle The puborectalis muscle (PRM) fibers arise from the lower part of the symphysis pubis and from the superior fascia of the urogenital diaphragm and run alongside the anorectal junction. Posterior to the rectum, the fibers join forming a sling. The “anorectal ring” is composed of the upper borders of the internal anal sphincter and puborectalis ­

­muscle [1]. Contraction of the PRM sling causes a ­horizontal force [19] that closes the pelvic diaphragm and decreases the ­ anorectal angle during squeeze. This is widely considered the most important contributing factor to gross fecal continence.

Iliococcygeus Muscle Iliococcygeus muscle (ICM) fibers arise from the ischial spines and posterior obturator fascia, pass inferior/posterior and medially, and insert into the distal sacrum, coccyx, and anococcygeal raphe. The ICM, along with the pubo­coccygeus muscle, contributes to “lifting” of the pelvic floor [19].

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J.C. Carmichael and S. Mills

Pubococcygeus Muscle

Anatomy of the Rectum

The pubococcygeus (PCM) muscle lies medial to the PRM. PCM fibers arise from the anterior half of the obturator fascia and the high posterior pubis. The PCM fibers are directed posterior/inferior and medially, where they intersect with fibers from the opposite side and form the anococcygeal raphe (or anococcygeal ligament). PCM muscle fibers insert in the distal sacrum and tip of the coccyx. Portions of the PCM contribute to the conjoined longitudinal muscle. The PCM forms the “levator hiatus” as it ellipses the lower rectum, urethra, and either the vagina in women or the dorsal vein of the penis in men. The levator hiatus is connected to the intrahiatal organs by a fascial condensation called the “hiatal ligament” (Figure 1-4). The hiatal ligament arises circumferentially around the hiatal margin as a continuation of the fascia on the pelvic surface of the levator muscle [23]. Enlargement of the levator hiatus has been implicated as a cause of female pelvic organ prolapse [24]. The PCM is the portion of the levator ani that is typically injured during traumatic vaginal delivery [25].

The rectum is arbitrarily considered to have three distinct parts: the upper, middle, and lower rectum. Although not anatomically distinct, the upper, mid, and lower rectal divisions are important when considering surgical treatment of rectal cancer. From the anal verge, the lower rectum is 0–7 cm; middle rectum, 7–12 cm; and upper rectum 12–15 cm [26]. However, the rectum is actually variable in length and may extend beyond 15 cm from the anal verge. The upper rectum can be distinguished from the sigmoid colon by the absence of taenia coli and epiploic appendages. The majority of the rectum lies outside of the peritoneal cavity, although anteriorly and laterally the upper rectum is covered by a layer of visceral peritoneum down to the peritoneal reflection. The location of the anterior peritoneal reflection is highly variable and can be significantly altered by disease such as rectal prolapse. One study sought to identify the location of the anterior peritoneal reflection in 50 patients

Pubococcygeus

Puborectalis

Hiatal ligament

Dorsal vein of penis Levator hiatus Obturator internus

Piriformis

Figure 1-4.  Pelvic floor anatomy, abdominal view.

Urethra Pubococcygeus Anorectal junction Anococcygeal raphe

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

who were undergoing laparotomy [27]. It was found that the anterior peritoneal reflection was located on average 9 cm from the anal verge in females and 9.7 cm from the anal verge in males—there was no statistically significant difference based on gender.

blood vessels, and nerves and is not considered a barrier strong enough to prevent the spread of infection or ­malignancy [32].

Presacral Fascia Mesorectum The origin of the word “mesorectum” is difficult to identify and may be attributed to Maunsell in 1892 [28], but was ­certainly later popularized by Heald [29]. Unfortunately, the term mesorectum is a misnomer that is not generally acknowledged in classic texts of anatomy such as the Nomina Anatomica [30]. In anatomic terms, the prefix “meso” refers to two layers of peritoneum that suspend an organ and the suffix applied indicates the target organ (e.g., mesocolon). The term “meso” cannot be assigned to the rectum, as it implies a mobile, suspended rectum, which may only be the case in patients with rectal prolapse. The mesorectum is a term employed by surgeons to describe the fascial envelope of the rectum that is excised during surgical treatment of rectal cancer. Indeed, failure to completely excise this envelope intact has been associated with an increased incidence of local recurrence of rectal cancer [31]. The mesorectum is contained within the fascia propria. The fascia propria is an upward projection of the parietal endopelvic fascia that lines the walls and floor of the pelvis. The fascia propria encloses the perirectal fat, lymphatics,

The presacral fascia is a thickened portion of the parietal endopelvic fascia overlying the sacrum that covers the presacral veins and hypogastric nerves (Figure 1-5). It extends laterally to cover the piriformis and upper coccyx. As the presacral fascia extends laterally, it becomes continuous with the fascia propria and contributes to the lateral ligaments of the rectum. Caudally, this fascia extends to the anorectal junction covering the anococcygeal ligament. During total mesorectal excision, the fascia propria is elevated sharply off the presacral fascia. Leaving the presacral fascia intact eliminates the possibility of causing presacral bleeding.

Retrosacral Fascia The retrosacral fascia originates at the third and fourth portion [33] of the sacrum and extends anteriorly to the posterior layer of the fascia propria 3–5 cm proximal to the anorectal junction [34]. This tough fascia layer is surgically relevant as it must be sharply incised during total mesorectal excision [32]. The space posterior to the retrosacral fascia is referred to as the supralevator or retrorectal space.

Rectovesical pouch

Peritoneum Presacral fascia

Retrosacral fascia

Denonvilliers’ fascia Anterior mesorectum

Prostate Seminal vesicles

Figure 1-5.  Fascial relationships of the rectum.

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Waldeyer’s Fascia There is significant confusion about what Waldeyer’s fascia represents as the eponym has been used to describe the presacral fascia, the retrosacral fascia or all fascia posterior to the rectum. In Waldeyer’s original description of pelvic ­fascia, there was no particular emphasis on the presacral component [32, 34]. While the debate continues regarding “Waldeyer’s fascia,” it is important to simply understand that the phrase can have the potential to mean presacral fascia, rectosacral, or retrorectal fascia [35].

Denonvilliers’ Fascia Denonvilliers’ fascia arises from the fusion of the two walls of the embryological peritoneal cul-de-sac and extends from the deepest point of the rectovesical pouch to the pelvic floor [36]. Originally described by Denonvilliers in 1836 as a “prostatoperitoneal” membranous layer between the rectum and seminal vesicles, Denonvilliers’ fascia is also present in females as part of the rectovaginal septum and is sometimes referred to as rectovaginal fascia. It is found immediately beneath the vaginal epithelium and is clearly what most would consider as part of the vaginal wall. It merges superiorly with the cardinal/ uterosacral complex in females or the rectovesical pouch in males. It merges laterally with the endopelvic fascia overlying the levator muscle and ­distally with the perineal body. It contains collagen, some strands of smooth muscle and heavy elastin fibers. Rectoceles represent a defect in this layer that allows the rectum to bulge anteriorly [37]. Microscopically, the Denonvilliers’ fascia has two layers; however, it is not possible to discern two layers during pelvic dissection [36]. In the anterior rectal plane, the mesorectum is contained by the fascia propria which lies dorsal to Denon­ villiers’ fascia. The cavernous nerves run in n­eurovascular bundles at the anterolateral border of Denonvilliers’ fascia.

J.C. Carmichael and S. Mills

carcinoma as possible,” Heald does not mention “lateral ligaments” of the rectum at all [39]. In an extensive review of the anatomy of the lateral ligament, Church notes that it is a common misconception that the lateral ligaments contain the middle rectal artery at all. It appears that the lateral ligaments comprise “primarily nerves and connective tissue” and their division without bleeding attests to the absence of a “significant accessory rectal artery in this location in the majority of patients” [32]. In a separate cadaveric study, the lateral ligaments of the rectum were identified as trapezoid structures originating from mesorectum and anchored to the endopelvic fascia at the level of the midrectum. It was recommended that, as lateral extensions of the mesorectum, the ligaments must be cut and included in the total mesorectal excision (TME) specimen. It was further noted that the lateral ligaments did not contain middle rectal arteries or nerve structures of importance. The urogenital bundle runs just above the lateral ligament at its point of insertion on the endopelvic fascia, the middle rectal artery (if present) runs posterior to the lateral ligament and the nervi recti fibers (which originate from the inferior hypogastric plexus) course transversely under the lateral ligament to the rectal wall [40]. Other modern cadaveric investigations note the rarity of middle rectal arteries and the absence of clinically relevant neurovascular structures in the lateral ligaments [41].

Valves of Houston The rectum has been classically described to have three distinct, semicircular, inner folds called valves of Houston (Figure 1-1) with the superior and inferior valves located on the left side of the rectum and the more prominent middle rectal valve on the right; however, this is not uniformly the case [42]. Only 45.5% of patients will have the classic three valve rectal anatomy; 32.5% will have only two valves; and, 10.25% may have four valves.

Lateral Ligaments While frequently referred to by surgeons, there are two controversial points regarding the lateral ligaments of the rectum. First, do the lateral ligaments exist? Second, what do they contain? Miles refers to division of the lateral ligaments of the rectum in his seminal description of abdominoperineal resection in 1908. Specifically, he notes “In these structures the middle hemorrhoidal arteries are found but seldom require a ligature” [38]. It is interesting to note that at least one modern cadaveric dissection study identified the presence of a middle rectal artery in only 22% of specimens [33] which could be a contributing factor as to why Miles saw no significant bleeding in this area. Total mesorectal excision, as popularized and described by Heald involves sharp dissection along the fascia propria circumferentially to the pelvic floor. While acknowledging that the middle rectal vessels are “divided as far from the

Anorectal Spaces It is important to acknowledge and understand the anorectal spaces created by the various myofascial relationships in the pelvis as these spaces help us understand how anorectal sepsis can spread throughout the pelvis.

Perianal Space The perianal space contains external hemorrhoid cushions, the subcutaneous external anal sphincter and the distal internal anal sphincter. The perianal space is in communication with the intersphincteric space (Figure 1-6). The perianal space has its cephalad boundary at the dentate line and laterally to the subcutaneous fat of the buttocks or is contained by fibers

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

Peritoneum Levator ani muscle Obturator internus muscle

Supralevator space Pudendal (Alcock’s) canal

Internal anal sphincter muscle

Ischioanal space

Puborectalis muscle

Intersphincteric space

External anal sphincter muscle

Transverse fibrous septum of ischiorectal fossa Perianal space

Figure 1-6.  Perianal and perirectal spaces, coronal view.

extending from the conjoined longitudinal muscle often referred to as corrugator cutis ani muscle fibers. Otherwise, the perianal space is contained by anoderm.

Intersphincteric Space The intersphincteric space is the potential space that lies between the internal and external anal sphincter and is continuous with the perianal space. It is of clinical importance as cryptoglandular infections tend to begin in this area and expand elsewhere to create anal fistula [4].

Submucous Space This space lies between the medial boarder of the internal anal sphincter and the anal mucosa proximal to the dentate line. It is continuous with the submucosa of the rectum. This area contains internal hemorrhoid vascular cushions.

Ischioanal/Ischiorectal Space The ischioanal (also referred to as ischiorectal) space is the largest anorectal space. It has been described as a pyramid shape with its apex at the levator muscle insertion into the obturator fascia. The medial boarder is thus the levator ani muscle and external anal sphincter. The obturator internus muscle and obturator fascia make up the lateral boarder of the ischioanal space. The posterior boundary is formed by the lower border of the gluteus maximus muscle and the sacrotuberous ligament. The space is has an anterior

b­ oundary formed by the superficial and deep transverse perineal muscles. The caudal boundary is skin of the perineum. The ischioanal fossa contains adipose tissue, pudendal nerve branches and superficial branches of the internal pudendal vessels. The right and left ischioanal space communicate posteriorly through the deep postanal space between the levator ani muscle and anococcygeal ligament (Figure 1-7) [43]. When the ischioanal and perianal spaces are regarded as a single space, it is referred to as the ischioanal fossa [35].

Supralevator Space The upper boundary of the supralevator space is the peritoneum, the lateral boundary is the pelvic wall, the medial boundary is the rectum and the inferior boarder is the levator ani muscle (Figure 1-8).

Superficial and Deep Postanal Spaces These spaces are located posterior to the anus and inferior to the levator muscle. The superficial postanal space is more caudal and is located between the anococcygeal ligament and the skin. The superficial postanal space allows communication of perianal space sepsis. The deep postanal space (retrosphincteric space of Courtney) [44] is located between the levator ani muscle and the anococcygeal raphe. This space allows ischioanal sepsis to track from one side to the other resulting in the so called “horseshoe” abscess.

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Supralevator space Ischioanal space Intersphincteric space

Figure 1-7.  Communication of the anorectal spaces.

Retrorectal space Retrosacral fascia Supralevator space Levator ani muscle Deep postanal space Anococcygeal ligament Superficial postanal space

Figure 1-8.  Perianal and perirectal spaces, lateral view.

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

Retrorectal Space The retrorectal space is found between the presacral fascia and fascia propria. It contains no major blood vessels or nerves. It is limited laterally by the lateral ligaments of the piriformis fascia and inferiorly by the retrosacral fascia. The fascia propria and presacral fascia come together at the apex of this space [32].

[45] of cases as it descends caudally in the m ­ esorectum. On average, eight terminal branches of the SRA have been identified in the distal rectal wall [46].

Middle Rectal Artery

The rectum is supplied by the superior, middle, and inferior rectal (hemorrhoidal) arteries (Figure 1-9). Both the middle and inferior hemorrhoidal vessels are paired arteries and the superior rectal artery is not.

The middle rectal artery (MRA) has been variably noted in many studies. It may be found on one or both sides of the rectum and has been noted to be present 12–28% of the time [41, 47]. At least one study reported the presence of the middle rectal artery in at least 91% of cadaveric specimens [40]. The MRA originates from the anterior division of the i­ nternal iliac or pudendal arteries. Please see the “Lateral Ligament” discussion above for more review on the anatomic course of the middle rectal artery.

Superior Rectal Artery

Inferior Rectal Artery

The superior rectal artery (SRA) is the continuation of the inferior mesenteric artery and is so named after the inferior mesenteric artery crosses the left iliac vessels. The SRA gives off a rectosigmoid branch, an upper rectal branch, and then bifurcates into right and left terminal branches in 80%

The inferior rectal arteries (IRA) are paired vessels that ­originate as branches of the internal pudendal artery which receives its blood supply from the internal iliac artery. The artery originates in the pudendal canal and is entirely extra-­ pelvic (caudal to the levator ani) in its distribution. The IRA

Rectal Blood Supply

Arc of Riolan Superior mesenteric artery Middle colic artery

Ascending branch of left colic artery

Right colic artery

Inferior mesenteric artery

Ileocolic artery

Marginal artery Left colic artery Sigmoid arteries

Internal iliac artery

Common iliac artery Superior rectal artery Median sacral artery

Middle rectal artery Inferior rectal artery

Figure 1-9.  Arterial anatomy of the colon and rectum.

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J.C. Carmichael and S. Mills

Portal vein

Superior mesenteric vein

Right colic vein

Splenic vein

Inferior mesenteric vein

Left colic vein

Ileocolic vein

Sigmoid vein

Common iliac vein

Middle sacral vein

Right external iliac vein

Superior rectal vein

Internal iliac vein

Middle rectal vein Inferior rectal vein

Figure 1-10.  Venous anatomy of the colon and rectum.

traverses the obturator fascia, the ischiorectal fossa and pierces the wall of the anal canal in the region of the external anal sphincter [32].

lymph nodes. In the anal canal, lymphatic above the dentate drain to the inferior mesenteric and internal iliac lymph nodes. Below the dentate line lymphatics drain along the inferior rectal lymphatics to the superficial inguinal nodes.

 enous and Lymphatic Drainage of the Rectum V and Anus

Innervation of the Rectum and Anus

Venous drainage from the rectum and anus occurs via both the portal and systemic systems. Middle and inferior rectal veins drain to the systemic systems via the internal iliac vein while the superior rectal vein drains the rectum and upper anal canal into the portal system via the inferior mesenteric vein (Figure 1-10). Lymphatics from the upper two-thirds of the rectum drain to the inferior mesenteric lymph nodes and then to the para-­ aortic lymph nodes. Lymphatic drainage from the lower third of the rectum occurs along the superior rectal artery and ­laterally along the middle rectal artery to the internal iliac

Sympathetic fibers arise from L1, L2, and L3 and pass through the sympathetic chains and join the pre-aortic plexus (Figure 1-11). From there, they run adjacent and dorsal to the inferior mesenteric artery as the mesenteric plexus and innervate the upper rectum. The lower rectum is innervated by the presacral nerves from the hypogastric plexus. Two main hypogastric nerves, on either side of the rectum, carry sympathetic information form the hypogastric plexus to the ­pelvic plexus. The pelvic plexus lies on the lateral side of the pelvis at the level of the lower third of the rectum adjacent to the lateral stalks (please see discussion of lateral stalks above).

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

Sympathetic trunk Superior hypogastric plexus (sympathetic) Pelvic splanchnic nerves (nervi erigentes)

Pelvic plexus

Pudendal nerve Dorsal nerve of penis

Inferior rectal nerve

Perineal nerve

Figure 1-11.  Nerves of the rectum.

Parasympathetic fibers to the rectum and anal canal o­ riginate from S2, S3, and S4 to penetrate through the sacral foramen and are called the nervi erigentes. These nerves course laterally and anterior to join the sympathetic hypogastric nerves and form the pelvic plexus on the pelvic sidewall. From here, postganglionic mixed parasympathetic and sympathetic nerve fibers supply the rectum, genital organs, and anal canal. The periprostatic plexus is considered a ­subdivision of the pelvic plexus and supplies the prostate, seminal vesicles, corpora cavernosa, vas deferens, urethra, ejaculatory ducts, and bulbourethral glands. The internal anal sphincter is innervated by sympathetic (L5) and parasympathetic (S2, S3, and S4) nerves following the same route as the nerves to the rectum as noted above. The external anal sphincter is innervated on each side by the inferior rectal branch of the internal pudendal nerve (S2 and S3) and by the perineal branch of S4. Anal sensation is mediated by the inferior rectal branch of the pudendal nerve.

Anatomy of the Colon The colon is a long tubular organ consisting of muscle and connective tissue with an inner mucosal layer. The diameter of the colon differs depending upon which segment is

e­ valuated, and generally decreases in diameter as one travels proximal to distal (cecum about 7 cm and sigmoid colon about 2.5 cm in diameter). The overall length is variable with an average length approximating 150 cm. The right and left sides of the colon are fused to the posterior retroperitoneum (secondarily retroperitonealized) while the transverse colon and sigmoid colon are relatively free within the peritoneum. The transverse colon is held in position via its attachments to the right/left colon at the flexures (hepatic and splenic, respectively) and is further fused to the omentum. Generally speaking the colon is located peripherally within the abdomen with the small bowel located centrally. There are three important anatomic points of differen­ tiation between the colon and the small intestine: the ­appendices epiploicae, the taeniae coli, and the haustra. The appendices epiploicae are non-mesenteric fat protruding from the serosal surface of the colon. They are likely residual from the anti-mesenteric fat of the embryologic intestine which dissipates (unlike the omentum on the stomach). The taenia coli are three thickened bands of outer, longitudinal muscle of the colon. This outer layer of muscle is indeed circumferentially complete [48], but is considerably thicker in three areas represented by the taenia. The three taeniae have been given separate names by some: taenia libera to represent the anterior band, taenia mesocolica for the

16

p­ osteromedial band, and taenia omentalis for posterolateral band. The bands are continuous from their origin at the base of the appendix until the rectosigmoid junction where they converge (marking an anatomically identifiable differentiation between the sigmoid colon and rectum). Though they run along the full length of the colon, they are not as long as the bowel wall. This difference in length results in outpouchings of the bowel wall between the taenia referred to as haustra. The haustra are further septated by the plicae semilunares.

Cecum The proximal most portion of the colon is termed the cecum, a sac-like segment of colon below (proximal to) the ileocecal valve. The cecum is variable in size, but generally is about 8 cm in length and 7 cm in diameter. At its base is the appendix. Terminating in the posteromedial area of the cecum is the terminal ileum (ileocecal valve). The cecum is generally covered by visceral peritoneum, with more variability near the transition to the ascending colon (upper or distal cecum). The ileocecal valve is a circular muscular sphincter which appears as a slit-like (“fish-mouth”) opening noted on an endoscopic evaluation of the cecum. The valve is not competent in all patients, but when present, its competence leads to the urgency of a colon obstruction as it develops into a closed-loop obstruction. Regulation of ileal emptying into the colon appears to be the prime task in ileocecal valve function [49].

The Appendix The appendix is an elongated, true diverticulum arising from the base of the cecum. The appendiceal orifice is generally about 3–4 cm from the ileocecal valve. The appendix itself is of variable length (2–20 cm) and is about 5 mm in diameter in the non-inflamed state. Blood is supplied to the appendix via the appendiceal vessels contained within the mesoappendix. This results in the most common location of the appendix being medially on the cecum toward the ileum, but the appendix does have great variability in its location including pelvic, retrocecal, preileal, retroileal, and subcecal.

Ascending Colon From its beginning at the ileocecal valve to its terminus at the hepatic flexure where it turns sharply medially to become the transverse colon, the ascending colon measures on average, about 15–18 cm. Its anterior surface is covered in visceral peritoneum while its posterior surface is fused with the retroperitoneum. The lateral peritoneal reflection can be seen as a thickened line termed the white line of Toldt, which can serve as a surgeon’s guide for mobilization of the ascending colon off of its attachments to the retroperitoneum, most

J.C. Carmichael and S. Mills

notably the right kidney (Gerotta’s fascia) and the loop of the duodenum located posterior and superior to the ileocolic vessels. The right ureter and the right gonadal vessels pass posteriorly to the ascending mesocolon within the retroperitoneum.

Transverse Colon The transverse colon traverses the upper abdomen from the hepatic flexure on the right to the splenic flexure on the left. It is generally the longest section of colon (averaging 45–50 cm) and swoops inferiorly as it crosses the abdomen. The entire transverse colon is covered by visceral peritoneum, but the greater omentum is fused to the anterosuperior surface of the transverse colon. Superior to the transverse mesocolon, inferior to the stomach, and posterior to the omentum is the pocket of the peritoneal cavity termed the lesser sac, with the pancreas forming the posterior most aspect. The splenic flexure is the sharp turn from the transversely oriented transverse colon to the longitudinally oriented descending colon. It can be adherent to the spleen and to the diaphragm via the phrenocolic ligament.

Descending Colon The descending colon travels inferiorly from the splenic flexure for the course of about 25 cm. It is fused to the retroperitoneum (similarly to the ascending colon) and overlies the left kidney as well as the back/retroperitoneal ­musculature. Its anterior and lateral surfaces are covered with visceral peritoneum and the lateral peritoneal reflection (white line of Toldt) is again present.

Sigmoid Colon The sigmoid colon is the most variable of the colon segments. It is generally 35–45 cm in length. It is covered by visceral peritoneum, thereby making it mobile. Its shape is considered “omega-shaped” but its configuration and attachments are variable. Its mesentery is of variable length, but is fused to the pelvic walls in an inverted-V shape creating a recess termed the intersigmoid fossa. Through this recess travel the left ureter, gonadal vessels, and often the left colic vessels.

Rectosigmoid Junction The end of the sigmoid colon and the beginning of the rectum is termed the rectosigmoid junction. It is noted by the confluence of the taeniae coli and the end of epiploicae appendices. While some surgeons have historically considered the rectosigmoid junction to be a general area (comprising about 5 cm

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus

of distal sigmoid and about 5 cm of proximal rectum), others have described a distinct and clearly defined segment. It is the narrowest portion of the large intestine, measuring 2–2.5 cm in diameter. Endoscopically, it is noted as a narrow and often sharply angulated area above the relatively capacious rectum, and above the three rectal valves. In the early nineteenth century, it was proposed that the sigmoid acts as a reservoir for stool, thus aiding in continence [50]. Subsequently, an area of thickened circular muscle within the wall of the rectosigmoid was described and felt to function as a sphincter of sorts. Historically, it has been variably named the sphincter ani tertius, rectosigmoid sphincter, and pylorus sigmoidorectalis [51–55]. A more recent evaluation of the rectosigmoid junction utilizing anatomic and histologic studies as well as radiographic evaluation concluded that there was an anatomic sphincter at the rectosigmoid junction [56]. Microscopic evaluation of the area does reveal thickening of the circular muscle layer as it progresses toward the rectum. Though not identifiable externally, radiologic evaluation can identify the area as a narrow, contractile segment [56].

Blood Supply The colon receives blood supply from two main sources, branches of the Superior Mesenteric Artery (SMA) (cecum, ascending, and transverse colon) and branches of the Inferior Mesenteric Artery (IMA) (descending and sigmoid colon) (Figure  1-9). There is a watershed area between these two main sources located just proximal to the splenic flexure where branches of the left branch of the middle colic artery anastomose with those of the left colic artery. This area represents the border of the embryologic midgut and hindgut. Though the blood supply to the colon is somewhat variable, there are some general common arteries. The cecum and right colon are supplied by the terminus of the SMA, the ileocolic artery. The right colic artery is less consistent and, when present, can arise directly from the SMA, from the ileocolic, or from other sources. The transverse colon is supplied via the middle colic artery, which branches early to form right and left branches. The middle colic artery originates directly from the SMA. The left colon and sigmoid colon are supplied by branches of the IMA, namely the left colic and a variable number of sigmoid branches. After the final branches to the sigmoid colon, the IMA continues inferiorly as the superior hemorrhoidal (rectal) artery.

Superior Mesenteric Artery The superior mesenteric artery (SMA) is the second, unpaired anterior branch off of the aorta (Figure 1-9). It arises posterior to the upper edge of the pancreas (near the L1 vertebrae), courses posterior to the pancreas, and then crosses over the third portion of the duodenum to continue within the base of

the mesentery. From its left side, the SMA gives rise to up to 20 small intestinal branches while the colic branches ­originate from its ride side. The most constant of the colic branches is the ileocolic vessel which courses through the ascending mesocolon where it divides into a superior (ascending) branch and an inferior (descending) branch [57]. A true right colic artery is absent up to 20% of the time and, when present, typically arises from the SMA. Alternatively, the right colic artery can arise from the ileocolic vessels or from the middle colic vessels [45, 57, 58]. The middle colic artery arises from the SMA near the inferior border of the pancreas. It branches early to give off right and left branches. The right branch supplies the hepatic flexure and right half of the transverse colon. The left branch supplies the left half of the transverse colon to the splenic flexure. In up to 33% of patients, the left branch of the middle colic artery can be the sole supplier of the splenic flexure [57, 59].

Inferior Mesenteric Artery The inferior mesenteric artery (IMA) (Figure 1-9) is the third unpaired, anterior branch off of the aorta, originating 3–4 cm above the aortic bifurcation at the level of the L2 to L3 vertebrae. As the IMA travels inferiorly and to the left, it gives off the left colic artery and several sigmoidal branches. After these branches, the IMA becomes the superior hemorrhoidal (rectal) artery as it crosses over the left common iliac artery. The left colic artery divides into an ascending branch (splenic flexure) and a descending branch (the descending colon). The sigmoidal branches form a fairly rich arcade within the sigmoid mesocolon (similar to that seen within the small bowel mesentery). The superior hemorrhoidal artery carries into the mesorectum and into the rectum. The superior hemorrhoidal artery bifurcates in about 80% of patients.

 he Marginal Artery and Other Mesenteric T Collaterals The major arteries noted above account for the main source of blood within the mesentery. However, the anatomy of the mesenteric circulation and the collaterals within the mesentery remain less clear. Haller first described a central artery anastomosing all mesenteric branches in 1786 [60]. When Drummond demonstrated its surgical significance in the early twentieth century, it became known as the marginal artery of Drummond [61, 62]. The marginal artery (Figure 1-9) has been shown to be discontinuous or even absent in some patients, most notably at the splenic flexure (Griffiths’ critical point), where it may be absent in up to 50% of patients [63]. This area of potential ischemia is the embryologic connection between the midgut and hindgut. Inadequacy of the marginal artery likely accounts for this area being most severely affected in cases of colonic ischemia. Another potential (though controversial) site of ischemia is at a discontinuous

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area of marginal artery located at the rectosigmoid junction termed Sudeck’s critical point. Surgical experience would question whether this potential area of ischemia exists; a recent fluorescence study indicates that it does [64], though its clinical importance remains in doubt.

Venous Drainage Venous drainage of the colon largely follows the arterial ­supply with superior and inferior mesenteric veins draining both the right and left halves of the colon (Figure 1-10). They ultimately meet at the portal vein to reach the intrahepatic system. The superior mesenteric vein (SMV) travels parallel and to the right of the artery. The inferior mesenteric vein (IMV) does not travel with the artery, but rather takes a longer path superiorly to join the splenic vein. It separates from the artery within the left colon mesentery and runs along the base of the mesentery where it can be found just lateral to the ligament of Treitz and the duodenum before joining the splenic vein on the opposite (superior) side of the transverse mesocolon. Dissecting posterior to the IMV can allow for separation of the mesenteric structures from the retroperitoneal structures during a medial-to-lateral dissection.

Lymphatic Drainage The colon wall has a dense network of lymphatic plexuses. These lymphatics drain into extramural lymphatic channels which follow the vascular supply of the colon. Lymph nodes are plentiful and are typically divided into four main groups. The epiploic group lies adjacent to the bowel wall just below the peritoneum and in the epiploicae. The paracolic nodes are along the marginal artery and the vascular arcades. They are most filtering of the nodes. The intermediate nodes are situated on the primary colic vessels. The main or principal nodes are on the superior and inferior mesenteric vessels. Once the lymph leaves the main nodes, it drains into the cisterna chili via the para-aortic chain.

Nervous Innervation The colon is innervated by the sympathetic and parasympathetic nervous systems and closely follows the arterial blood supply. The sympathetic innervation of the right half of the colon originates from the lower six thoracic splanchnic nerves which synapse within the celiac, pre-aortic, and ­superior mesenteric ganglia. The post-ganglionic fibers then follow the SMA to the right colon. The sympathetic inner­ vation for the left half originates from L1, L2, and L3.

J.C. Carmichael and S. Mills

Parasym­pathetic fibers to the right colon come from the ­posterior (right) branch of the Vagus Nerve and celiac plexus. They travel along the SMA to synapse with the nerves within the intrinsic autonomic plexuses of the bowel wall. On the left side, the parasympathetic innervation comes from S2, S3, and S4 via splanchnic nerves.

Embryology The embryologic development of the GI system is complex. That said, however, a working knowledge of the development of the small bowel, colon, and anorectum is critical for a colorectal surgeon as it can aid in understanding pathophysiology and is essential for recognizing surgical planes.

Anus and Rectum The colon distal to the splenic flexure, including the rectum and the anal canal (proximal to the dentate line), are derived from the hindgut and therefore have vascular supply from the inferior mesenteric vessels (Figure 1-9). The dentate line (Figure 1-1) is the fusion plane between the endodermal and ectodermal tubes. The cloacal portion of the anal canal has both endodermal and ectodermal components which develop into the anal transitional zone [65]. The terminal portion of the hindgut or cloaca fuses with the proctodeum (an ingrowth from the anal pit). The cloaca originates at the portion of the rectum below the pubococcygeal line while the hindgut originates above it. Before the fifth week of development, the intestinal and urogenital tracts are joined at the level of the cloaca. By the eighth week, the urorectal septum migrates caudally to divide the cloacal closing plate into an anterior urogenital plate and a posterior anal plate. Anorectal rings result from a posterior displacement in the septum and the resultant smaller anal opening. By the tenth week, the anal tubercles fuse into a horseshoe shaped structure dorsally and into the perineal body anteriorly. The external anal sphincter forms from the posterior aspects of the cloacal sphincter earlier than the development of the internal sphincter. The internal sphincter develops from enlarging fibers of the circular muscle layer of the rectum [66]. The sphincters migrate during their development with the internal sphincter moving caudally while the external sphincter enlarges cephalad. ­ Meanwhile, the longitudinal muscle descends into the intersphincteric plane [6]. In females, the female genital organs form from the Müllerian ducts and join the urogenital sinus by the 16th week of development. In contrast, in males, the urogenital membrane obliterates with fusion of the genital folds while the sinus develops into the urethra.

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus Normal inestinal rotation 6 week gestation

8 week gestation

First stage

9 week gestation

Second stage

11 week gestation

12 week gestation

Third stage

Figure 1-12.  Summary of normal intestinal rotation during development.

Colon and Small Intestine The endodermal roof of the yolk sac develops into the primitive gut tube. This initially straight tube is suspended upon a common mesentery. By week 3 of development, it has three discernible segments; namely the foregut, midgut, and hindgut. The midgut starts below the pancreatic papilla to form the small intestine and the first half of the colon (all supplied

by the superior mesenteric artery). The distal colon and ­rectum, as well as the anal canal develop from the hindgut and are therefore supplied by the inferior mesenteric artery. There is a normal process by which the intestinal tract rotates (Figure 1-12). The first stage is the physiologic herniation of the midgut, the second stage is its return to the abdomen, and the third stage is the fixation of the midgut. Abnormalities in this normal process lead to various malfor-

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J.C. Carmichael and S. Mills

mations (see below). The physiologic herniation (first stage) occurs between weeks 6 and 8 of development. The primitive gut tube elongates over the superior mesenteric artery and bulges out through the umbilical cord (Figure 1-13). During the eighth week, these contents move in a counterclockwise fashion, turning 90° from the sagittal to the h­ orizontal plane (Figure 1-14). Anomalies at this stage are rare, but include situs inversus, duodenal inversion, and extroversion of the cloaca. During the second stage (tenth week of gestation),

Midline section, midline loop

Vitelline duct

Superior mesenteric artery

the midgut loops return to the peritoneal cavity and simultaneously rotate an additional 180° in the counterclockwise direction (Figure 1-15). The pre-arterial portion of the duodenum returns to the abdomen first, followed by the counterclockwise rotation around the superior mesenteric vessels, resulting in the duodenum lying behind them. The colon returns after the rotation, resulting in their anterior location. Anomalies in this stage are more common and result in nonrotation, malrotation, reversed rotation, internal hernia, and omphalocele. The third stage (fixation of the midgut) begins once the intestines have returned to the peritoneal cavity and end at birth. The cecum migrates to the right lower quadrant from its initial position in the upper abdomen (Figure 1-16). After the completion of this 270° counterclockwise rotation, fusion begins, typically at week 12–13. This results in fusion of the duodenum as well as the ascending and descending colon (Figure 1-17).

Major Anomalies of Rotation Non-rotation

Cecal diverticulum

Figure 1-13.  Elongation of the midgut loop.

The midgut returns to the peritoneum without any of the normal rotation. This results in the small intestine being on the right side of the abdomen and the colon on the left side (Figure  1-18). This condition can remain asymptomatic (a finding noted at laparoscopy or laparotomy) or result in volvulus affecting the entirety of the small intestine. The twist generally occurs at the duodenojejunal junction as well as the midtransverse colon.

Rotation of the midgut loop

Lateral view

90° 42 days

50 days 90°

Figure 1-14.  Rotation of the midgut loop.

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus Figure 1-15.  Return of the intestinal loop to the abdomen.

Return to the abdomen

180° 70 days

77 days 180°

Reversed Rotation

Later fetal period

Clockwise (rather than counterclockwise) rotation of the midgut results in the transverse colon being posterior to the superior mesenteric artery while the duodenum lies ­anterior to it.

Omphalocele Ascending colon

Descending colon

An omphalocele is, basically, the retention of the midgut within the umbilical sac and its failure to return to the peritoneal cavity.

Internal Hernias

Sigmoid colon Cecum and appendix

Internal hernias, as well as congenital obstructive bands, can cause congenital bowel obstructions. These are considered failures of the process of fixation (the third stage of rotation). This can be the result of an incomplete fusion of the mesothelium or when structures are abnormally rotated. ­ Retroperitoneal hernias can occur in various positions, most notably paraduodenal, paracecal, and intersigmoid.

Figure 1-16.  Later fetal development.

 ther Congenital Malformations of the Colon O and Small Intestine Malrotation

Proximal Colon Duplication

There is normal initial rotation, but the cecum fails to complete the normal 270° rotation around the mesentery. This results in the cecum being located in the mid-upper abdomen with lateral bands (Ladd’s bands) fixating it to the right abdominal wall (Figure 1-19). These bands can result in extrinsic compression of the duodenum.

There are three general types of colonic duplication: mesenteric cysts, diverticula, and long colon duplication [67]. Mesenteric cysts are lined with intestinal epithelium and variable amounts of smooth muscle. They are found within the colonic mesentery or posterior to the rectum (within the mesorectum). They may be closely adherent to the bowel

J.C. Carmichael and S. Mills

22 Plane of median section

Omental bursa

Plane of horizontal section

Horizontal section

Descending colon Ascending colon

Jejunum

Median section Liver

Lesser omentum

Upper recess omental bursa

Epiploic foramen

Omental bursa

Pancreas

Fused layers of greater omentum and transverse mesocolon

Duodenum Pyloric stomach Fused layers of greater omentum

Greater omentum Transverse colon and mesocolon

Figure 1-17.  Development of the mesentery and omental fusion.

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1.  Anatomy and Embryology of the Colon, Rectum, and Anus Nonrotation

Stomach Duodenum

parallel the functional colon and often share a common wall throughout most of their length. They usually run the entire length of the colon and rectum and there is an association with other genitourinary abnormalities.

Meckel’s Diverticulum

Jejunoileal loops Ascending colon Transverse colon Descending colon

Cecum

Figure 1-18.  Intestinal non-rotation. Intestinal Malrotation

A Meckel’s diverticulum is the remnant of the vitelline or omphalomesenteric duct (Figure 1-13). It arises from the antimesenteric aspect of the terminal ileum, most commonly within 50 cm of the ileocecal valve. They can be associated with a fibrous band connecting the diverticulum to the umbilicus (leading to obstruction) or it may contain ectopic ­ gastric mucosa or pancreatic tissue (leading to bleeding or perforation) (Figure 1-20). An indirect hernia containing a Meckel’s diverticulum is termed a Littre’s hernia. Meckel’s diverti­culum is generally asymptomatic and, per autopsy series, is found in up to 3% of the population [68]. Surgical compli­cations, which are more common in children than adults, include hemorrhage, obstruction, diverticulitis, perforation, and umbilical discharge. Generally, there is no hard indication for excision of an incidentally discovered Meckel’s diverticulum, though its removal is generally safe [69, 70].

Stomach

Duodenum

Ladd’s bands Cecum

Small intestine

Figure 1-19.  Intestinal malrotation.

wall or separate from it. They generally present as a mass or with intestinal obstruction as they enlarge. Diverticula can be found on the mesenteric or antimesenteric sides of the colon and are outpouchings of the bowel wall. They often contain heterotopic gastric or pancreatic tissue. Long colonic duplications of the colon are the rarest form of duplication. They

Figure 1-20.  Perforated Meckel’s diverticulum with fistula to ileum.

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J.C. Carmichael and S. Mills

Atresia of the Colon

Anorectal Agenesis

Colonic atresia, representing only 5% of all gastrointestinal atresias, is a rare cause of congenital obstruction. They are likely the result of vascular compromise during development [71]. They vary in severity from a membranous diaphragm blocking the lumen to a fibrous cord-like remnant, on to a complete absence of a segment [72].

Anorectal agenesis is the most common type of “imperforate anus.” More common in males, the rectum ends well caudal to the surface and the anus is represented by a dimple with the anal sphincter usually being normal in location. In most cases, there is a fistula to the urethra or vagina. High fistulae (to the vagina or urethra) with anorectal agenesis develop as early as the sixth or seventh week of gestation while the low fistulae (perineal) or anal ectopia develop later, in the eighth or ninth week of development.

Hirschsprung’s Disease This nonlethal anomaly, which is more common in males, results from the absence of ganglion cells within the myenteric plexus of the colon. It is caused by interruption of the normal migration of the neuroenteric cells from the neural crest before they reach the rectum. This results in dilation and hypertonicity of the proximal colon. The extent of the aganglionosis is variable, though the internal sphincter is always involved. Its severity is dependent upon the length of the involved segment. It is discussed fully in Chap. 64.

Anorectal Malformations Abnormalities in the normal development of the anorectum can be attributed to “developmental arrest” at various stages of normal development. These abnormalities are often noted in concert with spinal, sacral, and lower limb defects, as noted by Duhamel and theorized to be related to a “syndrome of caudal regression” [73]. Indeed, skeletal and urinary anomalies are associated in up to 70% [74], while digestive tract anomalies (e.g., tracheoesophageal fistula or esophageal stenosis), cardiac, and abdominal wall abnormalities are also noted in patients with anorectal anomalies. While these are discussed in detail in Chap. 64, a few notable traits are worth pointing out.

Anal Stenosis While anal stenosis in a newborn is relatively common, noted in 25–39% of infants, symptomatic stenosis is only noted in 25% of these children [75]. The majority of these children undergo spontaneous dilation in the first 3–6 months of life.

Membranous Atresia This very rare condition is characterized by the presence of a thin membrane of skin between the blind end of the anal canal and the surface. It is also termed the covered anus. It is more common in males.

Anal Agenesis The rectum develops to below the puborectalis where it either ends in an ectopic opening (fistula) in the perineum, vulva, or urethra, or it ends blindly (less commonly). The sphincter is present at its normal site.

Rectal Atresia or “High Atresia” In rectal atresia, the rectum and the anal canal are separated from one another by an atretic portion. It is embryologically the distal most type of colon atresia, but is still considered an anorectal disorder clinically.

Persistent Cloaca This rare condition, which only occurs in female infants, is the result of total failure of descent of the urorectal septum. It occurs at a very early stage of development.

Conclusion It is said that to understand abnormal, you must first understand the normal. No where is that more of a true statement than with human anatomy. Further, to understand the pathophysiology of colorectal and anorectal disease mandates a wide-ranging knowledge base of the underlying anatomy and embryology. To properly care for these patients, one must first have a strong foundation and understanding the anatomical “building blocks” of the human body. Acknowledgment This chapter was written by José Marcio Neves Jorge and Angelita Habr-Gama in the first and second editions of this textbook.

References 1. Milligan ETC, Morgan CN. Surgical anatomy of the anal canal: with special reference to anorectal fistulae. Lancet. 1934;2(5804):1150–6. 2. Nivatvongs S, Stern HS, Fryd DS. The length of the anal canal. Dis Colon Rectum. 1981;24(8):600–1. 3. Morren GL, Beets-Tan RG, van Engelshoven JM. Anatomy of the anal canal and perianal structures as defined by phasedarray magnetic resonance imaging. Br J Surg. 2001;88(11): 1506–12. 4. Parks AG. Pathogenesis and treatment of fistuila-in-ano. Br Med J. 1961;1(5224):463–9. 5. Lilius HG. Fistula-in-ano, an investigation of human foetal anal ducts and intramuscular glands and a clinical study of 150 patients. Acta Chir Scand Suppl. 1968;383:7–88.

1.  Anatomy and Embryology of the Colon, Rectum, and Anus 6. Barleben A, Mills S. Anorectal anatomy and physiology. Surg Clin North Am. 2010;90(1):1–15. Table of Contents. 7. Sboarina A, et al. Shape and volume of internal anal sphincter showed by three-dimensional anorectal ultrasonography. Eur J Radiol. 2012;81(7):1479–82. 8. Haas PA, Fox Jr TA. The importance of the perianal connective tissue in the surgical anatomy and function of the anus. Dis Colon Rectum. 1977;20(4):303–13. 9. Treitz W. Ueber einen neuen Muskel am Duodenum des Menschen, uber elsatische Sehnen, und einige andere anatomische Verhaltnisse. Vierteljahrschrift Praktische Heilkunde (Prager). 1853;37:133–44. 10. Chang SC, Shih JJM, Shih JYM, Lee HHC. Review of Treitz’s muscles and their implications in a hemorrhoidectomy and hemorrhoidopexy. Fu-Jen J Med. 2006;4(1):1–6. 11. Thomson WH. The nature of haemorrhoids. Br J Surg. 1975;62(7):542–52. 12. Goligher JC, Leacock AG, Brossy JJ. The surgical anatomy of the anal canal. Br J Surg. 1955;43(177):51–61. 13. Bollard RC, et al. Normal female anal sphincter: difficulties in interpretation explained. Dis Colon Rectum. 2002;45(2): 171–5. 14. Hussain SM, Stoker J, Lameris JS. Anal sphincter complex: endoanal MR imaging of normal anatomy. Radiology. 1995;197(3):671–7. 15. Wunderlich M, Swash M. The overlapping innervation of the two sides of the external anal sphincter by the pudendal nerves. J Neurol Sci. 1983;59(1):97–109. 16. Mittal RK, et al. Purse-string morphology of external anal sphincter revealed by novel imaging techniques. Am J Physiol Gastrointest Liver Physiol. 2014;306(6):G505–14. 17. DeLancey JO, et al. Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol. 2007;109(2 Pt 1):295–302. 18. Shafik A. New concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. II. Anatomy of the levator ani muscle with special reference to puborectalis. Invest Urol. 1975;13(3):175–82. 19. Betschart C, et al. Comparison of muscle fiber directions between different levator ani muscle subdivisions: in vivo MRI measurements in women. Int Urogynecol J. 2014;25(9): 1263–8. 20. Levi AC, Borghi F, Garavoglia M. Development of the anal canal muscles. Dis Colon Rectum. 1991;34(3):262–6. 21. Grigorescu BA, et al. Innervation of the levator ani muscles: description of the nerve branches to the pubococcygeus, iliococcygeus, and puborectalis muscles. Int Urogynecol J Pelvic Floor Dysfunct. 2008;19(1):107–16. 22. Wallner C, et al. Evidence for the innervation of the puborectalis muscle by the levator ani nerve. Neurogastroenterol Motil. 2006;18(12):1121–2. 23. Shafik A. A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. VIII. Levator hiatus and tunnel: anatomy and function. Dis Colon Rectum. 1979;22(8):539–49. 24. Andrew BP, et al. Enlargement of the levator hiatus in female pelvic organ prolapse: cause or effect? Aust N Z J Obstet Gynaecol. 2013;53(1):74–8.

25 25. DeLancey JO, et al. Comparison of the puborectal muscle on MRI in women with POP and levator ani defects with those with normal support and no defect. Int Urogynecol J. 2012;23(1):73–7. 26. Heald RJ, Moran BJ. Embryology and anatomy of the rectum. Semin Surg Oncol. 1998;15(2):66–71. 27. Najarian MM, et al. Determination of the peritoneal reflection using intraoperative proctoscopy. Dis Colon Rectum. 2004;47(12):2080–5. 28. Chapuis P, et al. Mobilization of the rectum: anatomic concepts and the bookshelf revisited. Dis Colon Rectum. 2002;45(1):1– 8. discussion 8–9. 29. Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg. 1982;69(10):613–6. 30. Nomina Anatomica. 6th ed. Singapore: Churchill Livingstone; 1989. 31. Quirke P, et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. 2009;373(9666):821–8. 32. Church JM, Raudkivi PJ, Hill GL. The surgical anatomy of the rectum—a review with particular relevance to the hazards of rectal mobilisation. Int J Colorectal Dis. 1987;2(3):158–66. 33. Sato K, Sato T. The vascular and neuronal composition of the lateral ligament of the rectum and the rectosacral fascia. Surg Radiol Anat. 1991;13(1):17–22. 34. Crapp AR, Cuthbertson AM. William Waldeyer and the rectosacral fascia. Surg Gynecol Obstet. 1974;138(2):252–6. 35. Gordon PH, Nivatvongs S. Principles and practice of surgery for the colon, rectum, and anus. 3rd ed. New York, NY: Informa Healthcare USA, Inc.; 2007. 36. Lindsey I, et al. Anatomy of Denonvilliers’ fascia and pelvic nerves, impotence, and implications for the colorectal surgeon. Br J Surg. 2000;87(10):1288–99. 37. Richardson AC. The rectovaginal septum revisited: its relationship to rectocele and its importance in rectocele repair. Clin Obstet Gynecol. 1993;36(4):976–83. 38. Corman ML. Classic articles in colonic and rectal surgery. A method of performing abdominoperineal excision for carcinoma of the rectum and of the terminal portion of the pelvic colon: by W. Ernest Miles, 1869–1947. Dis Colon Rectum. 1980;23(3):202–5. 39. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1(8496):1479–82. 40. Nano M, et al. Contribution to the surgical anatomy of the ­ligaments of the rectum. Dis Colon Rectum. 2000;43(11):1592– 7. discussion 1597–8. 41. Lin M, et al. The anatomy of lateral ligament of the rectum and its role in total mesorectal excision. World J Surg. 2010;34(3):594–8. 42. Abramson DJ. The valves of Houston in adults. Am J Surg. 1978;136(3):334–6. 43. Llauger J, et al. The normal and pathologic ischiorectal fossa at CT and MR imaging. Radiographics. 1998;18(1):61–82. quiz 146. 44. Courtney H. The posterior subsphincteric space; its relation to posterior horseshoe fistula. Surg Gynecol Obstet. 1949;89(2): 222–6.

26 45. Michaels NA, Siddharth P, Kornblith PL, Park WW. The variant blood supply to the small and large intestines: its importance in regional resections. A new anatomic study based on four hundred dissections with a complete review of the literature. J Int Coll Surg. 1963;39:127–70. 46. Schuurman JP, Go PM, Bleys RL. Anatomical branches of the superior rectal artery in the distal rectum. Colorectal Dis. 2009;11(9):967–71. 47. Ayoub SF. Arterial supply to the human rectum. Acta Anat (Basel). 1978;100(3):317–27. 48. Fraser ID, et al. Longitudinal muscle of muscularis externa in human and nonhuman primate colon. Arch Surg. 1981;116(1): 61–3. 49. Guyton AC. Textbook of medical physiology. Philadelphia, PA: WB Saunders; 1986. 50. O’Beirne J, editor. New views of the process of defecation and their application to the pathology and treatment of diseases of the stomach, bowels and other organs. Dublin: Hodges and Smith; 1833. 51. Hyrtl J. Handbuch der topographischen anatomie und ihrer praktisch medicinisch-chirurgischen anwendungen. II. Band. 4th ed. Wien: Braumüller; 1860. 52. Mayo WJ. A study of the rectosigmoid. Surg Gynecol Obstet. 1917;25:616–21. 53. Cantlie J. The sigmoid flexure in health and disease. J Trop Med Hyg. 1915;18:1–7. 54. Otis WJ. Some observations on the structure of the rectum. J Anat Physiol. 1898;32:59–63. 55. Balli R. The sphincters of the colon. Radiology. 1939;33: 372–6. 56. Shafik A, et al. Rectosigmoid junction: anatomical, histological, and radiological studies with special reference to a sphincteric function. Int J Colorectal Dis. 1999;14(4–5): 237–44. 57. Sonneland J, Anson BJ, Beaton LE. Surgical anatomy of the arterial supply to the colon from the superior mesenteric artery based upon a study of 600 specimens. Surg Gynecol Obstet. 1958;106(4):385–98. 58. Steward JA, Rankin FW. Blood supply of the large intestine. Its surgical considerations. Arch Surg. 1933;26:843–91. 59. Griffiths JD. Surgical anatomy of the blood supply of the distal colon. Ann R Coll Surg Engl. 1956;19(4):241–56.

J.C. Carmichael and S. Mills 60. Haller A. The large intestine. In: Cullen W, editor. First lines of physiology. A reprint of the 1786 edition, Sources of science, vol. 32. New York, NY: Johnson; 1966. p. 139–40. 61. Drummond H. Some points relating to the surgical anatomy of the arterial supply of the large intestine. Proc R Soc Med. 1913;7:185–93. 62. Drummond H. The arterial supply of the rectum and pelvic colon. Br J Surg. 1914;1:677–85. 63. Meyers CB. Griffiths’ point: critical anastomosis at the splenic flexure. Am J Roentgenol. 1976;126:77. 64. Watanabe J, et al. Evaluation of the intestinal blood flow near the rectosigmoid junction using the indocyanine green fluorescence method in a colorectal cancer surgery. Int J Colorectal Dis. 2015;30(3):329–35. 65. Skandalakis JE, Gray SW, Ricketts R. The colon and rectum. In: Skadalakis JE, Gray SW, editors. Embryology for surgeons. The embryological basis for the treatment of congenital anomalies. Baltimore, MD: Williams & Wilkins; 1994. p. 242–81. 66. Nobles VP. The development of the human anal canal. J Anat. 1984;138:575. 67. McPherson AG, Trapnell JE, Airth GR. Duplication of the colon. Br J Surg. 1969;56(2):138–42. 68. Benson CD. Surgical implications of Meckel’s diverticulum. In: Ravitch MM, Welch KJ, Benson CD, editors. Pediatric surgery. Chicago, IL: Year Book Medical Publishers; 1979. p. 955. 69. Zani A, et al. Incidentally detected Meckel diverticulum: to resect or not to resect? Ann Surg. 2008;247(2):276–81. 70. Park JJ, et al. Meckel diverticulum: the Mayo Clinic experience with 1476 patients (1950–2002). Ann Surg. 2005;241(3):529–33. 71. Fomolo JL. Congenital lesions: intussusception and volvulus. In: Zuidema GD, editor. Shackelford’s surgery of the alimentary tract. Philadelphia, PA: WB Saunders; 1991. p. 45–51. 72. Louw JH. Investigations into the etiology of congenital atresia of the colon. Dis Colon Rectum. 1964;7:471–8. 73. Duhamel B. From the mermaid to anal imperforation: The syndrome of caudal regression. Arch Dis Child. 1961;36(186): 152–5. 74. Moore TC, Lawrence EA. Congenital malformations of the rectum and anus. II. Associated anomalies encountered in a series of 120 cases. Surg Gynecol Obstet. 1952;95(3):281–8. 75. Brown SS, Schoen AH. Congenital anorectal stricture. J Pediatr. 1950;36(6):746–51.

2 Colonic Physiology Joshua I.S. Bleier and Kirsten Bass Wilkins

Key Concepts • Colonic innervation is supplied by both extrinsic and intrinsic pathways. The extrinsic pathways are derived from the autonomic nervous system including parasympathetic and sympathetic routes. Parasympathetic input is excitatory while sympathetic input is inhibitory to colonic motor function. The intrinsic colonic nervous system consists of the myenteric plexus. • Short chain fatty acids are produced by the colon as a result of the fermentation of complex carbohydrates by colonic flora. The SCFA, butyrate, is the primary energy source of the colon. • The colon absorbs sodium and water and secretes bicarbonate and potassium. Aldosterone mediates the process of active sodium absorption in the colon. • Colonic contractile events are divided into (1) segmental contractions and (2) propagated contractions (including low-amplitude and high-amplitude propagating contractions, LAPC and HAPC, respectively). The main function of HAPC is to propagate colonic contents towards the anus. • The Interstitial cells of Cajal (ICC) are the primary pacemaker cells governing the function of the enteric nervous system.

Introduction The colon plays a central role in gastrointestinal (GI) physiology. There are multiple functions that the colon and rectum serve. The primary role of the colon is one of absorption of excess water and electrolytes, serving to salvage valuable fluid and unabsorbed nutrients as well as to create solid stool. It also plays a central role in bacterial homeostasis, serving as a home to billions of commensal bacteria whose role is symbiotic in maintaining the health of the colonic epithelium. The rectum has evolved complicated and elegant mechanisms to store feces and accommodate it while

a­ llowing for the selective egress of stool or gas. Understanding the physiologic and histologic components of the colon and rectum are critical to understanding normal and pathologic states.

Embryology Understanding the embryology of the colon and rectum provides essential information for understanding its function. During the third and fourth weeks of gestation, the primitive gut arises from the cephalic caudal and lateral foldings of the dorsal endoderm lined yolk sac. The mucosa arises from the endodermal layer, however the muscular wall, connective tissue and outer serosal surface arises from the mesodermal layer. By the fourth week of gestation, three distinct regions have differentiated based on their blood supply. The midgut, supplied by the superior mesenteric artery, begins distal to the confluence of the common bile duct in the third portion of the duodenum and includes the proximal two-thirds of the transverse colon. This portion of the intestine maintains a connection to the yolk sac via the vitelline duct. Absence of its obliteration results in a Meckel’s diverticulum. The hindgut, which comprises the rest of the distal GI tract, includes the distal transverse colon, descending colon, sigmoid colon, and rectum. This is supplied by the inferior mesenteric artery (IMA). During the fifth week of gestation, the midgut undergoes a rapid elongation which exceeds the capacity of the abdominal cavity. This results in a physiologic herniation through the abdominal wall at the umbilicus. Through the sixth week, continued elongation results in a 90° counterclockwise rotation around the superior mesenteric artery (SMA). The small intestine continues its significant growth, forming loops, while the caudal end enlarges into the cecal bud. During the tenth week, herniated bowel returns to the abdominal cavity, completing an additional 180° counterclockwise loop which leaves the proximal small bowel on the left, and the colon on the right. The dorsal mesentery of

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_2

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the ascending and descending colon shortens and involutes resulting in secondary retroperitoneal fixation [1]. The embryology of the distal rectum is more complex. It initially begins as the cloaca which is a specialized area comprising endodermal and ectodermally derived tissue. The cloaca exists as a continuation between the urogenital and GI tracts, however, during the sixth week it begins to divide and differentiate into the anterior urogenital and posterior anorectal and sphincter components. At the same time, the urogenital and GI tracts become separated by caudal migration of the urogenital septum. During the tenth week, while the majority of the midgut is returning to the abdomen, the external anal sphincter is formed in the posterior cloaca as the descent of the urogenital septum becomes complete. The internal anal sphincter is formed during the 12th week by enlargement and specialization of the circular muscle layer of the rectum [1].

J.I.S. Bleier and K.B. Wilkins

Colonic Epithelial Cell Types

Three main cell types are present in the colonic epithelium including columnar epithelial cells, goblet cells, and enterochromaffin cells. Columnar epithelial and goblet cells comprise nearly 95% of the cells in the colonic epithelium. The surface and crypt epithelial cells can be differentiated from one another based on proliferative activity, degree of differentiation, and function. Crypt epithelium is highly proliferative, relatively undifferentiated, and secretes chloride. The surface epithelium in contrast has low proliferative activity, is well-differentiated, and is highly absorptive. In general, epithelial cells become increasingly differentiated the farther they are from the crypt base. Thus, the base of the crypts forms the source of continually regenerating epithelial cells. This polarization provides distinct histologic characteristics, which are easily identified on standard H and E staining (Figures 2-1 and 2-2). Recent evidence, however, indicates that ion absorption and secretion occurs at both the surface Colonic Anatomy and crypt levels [2]. The role of the enterochromaffin cells is discussed below. Introduction The cells responsible for the enteric nervous system, the The colonic epithelium has both absorptive and secretory enteric ganglia, are located in the submucosa, otherwise functions. The colon is highly efficient at absorbing sodium known as Meissner’s plexus. An additional layer of ganglia chloride, water, and short chain fatty acids. In addition, the are located between the inner circular and outer longitudinal colonic epithelium secretes bicarbonate, potassium chloride, muscle layers known as Auerbach’s plexus. The interstitial and mucus. The colonic epithelium is a typical electrolyte-­ cells of Cajal (ICC), are specialized, c-kit positive cells that transporting layer that is capable of moving large quantities of are thought to primarily serve as the pacemaker cell of the water and salt from the lumen towards the blood. Under nor- enteric nervous system, linking the colonic submucosa elecmal circumstances, the colon is presented with between 1 and trochemically with the myenteric plexi. These are the cells of 2 l of electrolyte-rich fluid per day. Under normal p­ hysiologic origin of GI stromal tumors (GISTs) which arise from the conditions, nearly 90% of this fluid is absorbed. The end colonic wall rather than the mucosa [3]. result is the excretion of feces that has a sodium con­centration that approximates 30 mmol/l and a potassium concentration of approximately 75 mmol/l. Under normal cir­cumstances, fecal and plasma osmolality are similar. Colonic epithelial cells are polarized and equipped with numerous ion channels, carriers, and pumps that are localized on both the luminal and basolateral membranes. Many transport proteins have been identified and their functions elucidated. While an in-depth discussion of these mechanisms is beyond the scope of this chapter, important aspects are highlighted below.

Colonic Wall Anatomy The luminal surface of the colon is lined by epithelium. Deep to this is the submucosal layer, rich in vascular and lymphatic supply. This is surrounded by the continuous inner circular muscle layer and the outer longitudinal muscle layer which has three condensations known as taenia coli. The serosa, or outer layer of the colon, is surrounded by visceral peritoneum.

Figure 2-1.  Normal colonic mucosa. H and E, 250×. The layers of the normal colonic wall are indicated by the brackets. Courtesy of Julieta E. Barroeta, MD.

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Figure 2-2.  Normal colonic mucosa. H and E, 1000×. Epithelial cells types are clearly visible including goblet cells and columnar epithelial cells. The crypts are the source of the continually regenerating mucosal cells. Courtesy of Julieta E. Barroeta, MD.

Colonic Flora By the time enteric contents reach the colon, the majority of nutrients have been digested and absorbed by the small intestine. This leaves a fluid rich in electrolytes, bile salts, and undigested starches. These are the primary substrates upon which the colon functions. The colon is home to an enormous quantity of autochthonous flora consisting of more than 400 species of bacteria. Feces contains as many as 1011–1012 bacteria/gram of stool, and these bacteria contribute to approximately 50% of fecal mass. The majority of these bacteria are anaerobes which feed on residual proteins and undigested carbohydrates. This microflora contributes several important functions to the host including metabolic support of the colonocyte and gut-associated lymphoid tissue (GALT), which contributes significantly to both innate and adaptive immunity. Bacteroides species compose the predominant bacterial type throughout the colon, and they are responsible for almost 2/3 of the bacteria within the proximal colon and 70% of the bacteria in the rectum. The other predominant species are facultative aerobes and comprise Escherichia, Klebsiella, Proteus, lactobacillus, and enterococci. Unlike the majority of the proximal GI tract, the colonic mucosa does not receive its primary nutrition from blood-borne nutrients. In the colon and rectum, luminal contents provide the primary substrate. The main source of the substrate is undigested dietary fiber. This is metabolized by colonic bacteria through the process of fermentation. Cellulose is a partially fermented starch, which leaves behind bulk, whereas fruit pectins are completely metabolized (clarify). The primary end products of this process include short chain fatty acids, including butyrate, and gas. Several of the common dietary complex carbohydrates, including lignin and psyllium, are not metabolized at all, but remain as

h­ ydrophilic molecules in stool. These lead to water retention and stool bulking. Butyrate is the main source of energy for the colonocyte. This provides the substrate necessary to maintain epithelial integrity and developmental functions that stimulate epithelial cell differentiation and immune function. Protein fermentation, or putrefaction, may result in the formation of potentially toxic metabolites including ­phenols, indoles, and amines. These toxic end products of bacterial metabolism can lead to mucosal injury, reactive hyperproliferation, and possible promotion of carcinogenesis. Increased stool bulk is felt to provide enhanced colonic transit resulting in decreased time of exposure of the colonic lumen to these toxins, as well as a decreased need for higher intracolonic pressures necessary for segmental motility, a process which may retard the development of diverticular disease. Taken together, these aspects are the reason for many of the recommendations for dietary supplementation with indigestible fiber [4].

 lectrolyte Regulation and Water E Absorption Sodium chloride absorption occurs by both electroneutral and electrogenic active transport mechanisms. While electroneutral absorption takes place in both the surface and crypt epithelium, electrogenic absorption appears to be confined to the surface epithelium. A majority of sodium chloride absorption occurs in the proximal colon and is driven primarily through electroneutral absorption by tightly coupled luminal Na+/H+ and Cl−/HCO3− exchange. This process is driven by the basolateral Na+-K+-ATPase resulting in 1 mol of ATP being hydrolyzed for every 3 mol of NaCl absorbed. Three types of Na+/H+ exchangers (NHE) have been identified in colonic epithelium. Similarly, several Cl− exchange mechanisms have been identified. The luminal Cl−/ HCO3− exchange is represented by the anion exchanger type 1 (AE1). A separate Cl−/OH− exchange is represented by a protein called DRA (downregulated in colonic adenomas). Human DRA mutations are responsible for congenital chloride diarrhea [2]. Epithelial cells in the distal colon participate in electrogenic absorption of sodium. The epithelial sodium channel (ENaC) mediates this absorption and is located on the luminal surface. Sodium is taken up by the ENaC on the luminal surface and is excreted on the basolateral side by the Na+-K+ATPase. Potassium is secreted on the luminal side and is driven by the electrogenic uptake of sodium. Chloride is absorbed through luminal cystic fibrosis conductance regulator (CFTR) and other chloride channels. Chloride is then excreted on the basolateral side via multiple mechanisms including KCL cotransporter (KCC1), Cl− channels, and Cl−/ HCO3− anion exchangers [2]. The net result is tight regulation of electrolyte secretion in excreted stool (Figure 2-3).

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Figure 2-3.  Schematic of ion-­transport channels in proximal and distal colonocytes. Courtesy of Robin Noel.

Regulation of sodium absorption is complex and multiple mechanisms are involved. One mechanism of sodium absorption regulation is by feedback inhibition. Namely, changes in intracellular sodium concentration during sodium chloride absorption downregulate ENaC activity. Blood pressure and potassium levels also regulate sodium absorption via angiotensin II. Aldosterone, a mineralocorticoid, is the final endocrine signal in the renin–angiotensin–aldosterone pathway that targets renal and colonic epithelium. Aldosterone is a steroid hormone that is synthesized in the zona glomerulosa of the adrenal cortex. Previously, it was thought that aldosterone regulated sodium absorption solely via luminal ENaC. However, aldosterone also increases activity of NHE3. Therefore, aldosterone plays a role in both electrogenic and electroneutral active sodium absorption. Early and late phase aldosterone genomic actions have been identified. In the first 1–6 h, aldosterone-induced proteins including serum and glucocorticoid-inducible kinase (Sgk), corticosteroid hormone-induced factor (CHIF), and K-Ras

(KRAS) increase the posttranslational activation of existing ion channels and other proteins involved in ion transport such as ENAc. In the late phase (>6 h), aldosterone acts via the upregulation of nuclear transcription of these receptors. In addition, electroneutral absorption is known to be regulated in response to some G protein-linked receptors, tyrosine kinase-coupled receptors, and protein kinases. For example, activation of protein kinase C, Ca2+/calmodulin-dependent kinase, and increases in cAMP inhibit NHE3 [2, 5]. Evidence also points towards the regulation of sodium absorption by CFTR. ENaC, NHE3, and CFTR are coexpressed in colonic epithelial cells and thus CFTR plays a role in both the electrogenic and electroneutral absorption of electrolytes. CFTR inhibits both electroneutral NaCl absorption as well as electrogenic Na+ absorption. In the crypts, CFTR is a cAMP-mediated chloride channel that is essential for chloride secretion. In patients with cystic fibrosis, mutations in CFTR result in both impaired chloride secretion and enhanced sodium absorption [2, 6].

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Along with the kidneys, the colon assists with potassium homeostasis through the absorption and secretion of potassium. Active potassium absorption is restricted to the distal colon and is mediated by H+-K+-ATPase [2]. Water is passively absorbed and can be transported by various pathways including through paracellular shunts and through transcellular flux potentially through aquaporin channels located on luminal and basolateral membrane ­surfaces [2].

Short Chain Fatty Acid Absorption As indicated earlier, short chain fatty acids (SCFA) are ­produced during fermentation of dietary fibers by luminal bacteria. The most common short chain fatty acids include acetate, proprionate, and butyrate. Short chain fatty acids are absorbed by nonionic diffusion and paracellular absorption in the proximal colon. Butyrate is the main energy source for the colonocyte. Butyrate also plays a major role in the stimulation of sodium chloride absorption and inhibition of chloride secretion. Absorption of SCFA plays a significant role in NaCl absorption presumably by the acidification of colonocytes and activation of luminal Na+/H+ exchangers. Chloride absorption is also upregulated by increased HCO3− production and stimulation of the luminal Cl−/HCO3− exchanger. This HCO3− luminal secretion is paramount in regulating luminal intestinal pH. It has been proposed that antibiotic associated diarrhea is secondary to decreased butyrate production resulting in net secretion of fluid [2, 7]. In addition to its role in ionic absorption, butyrate has several other important functions. Butyrate has a trophic effect and stimulates cell proliferation in the crypts. It also reduces the number and size of aberrant crypt foci. This is important as aberrant crypt foci are the earliest precursors of colonic neoplasms. In colon cancer cell lines, butyrate induces apoptosis and cell cycle arrest via inhibition of histone deacetylase. Butyrate also has an anti-inflammatory role primarily by inhibition of nuclear factor kB (NF-kB) in colonic epithelial cells. Some studies have implicated impaired butyrate metabolism in patients with ulcerative colitis. Butyrate stimulates the production of MUC2 mucin and thus may play a role in maintaining the colonic defense barrier. In addition, butyrate may play a role in intestinal motility by regulating gene expression in the enteric nervous system. Finally, butyrate may decrease visceral sensitivity [7, 8]. Despite, the benefits of butyrate discussed above, commercially available butyrate available for oral administration is limited by its short half-life, poor palatability, and side effects such as nausea and anorexia. Rectal formulations are most commonly utilized at this time. Prebiotics and probiotics

which produce butyrate are alternative methods of delivery. Prebiotics are nutrients (typically carbohydrates) that support the growth of probiotics bacteria. Probiotics are live bacteria that when consumed in sufficient quantities confer positive health benefits [7, 8].

 ecretory Role of the Colonic S Epithelium Another major function of the colonic epithelium is elec­ trolyte secretion. Electrolyte secretion may help transport mucus from the crypts and mucus secretion may be activated by an increase in intracellular cAMP that parallels electrolyte secretion. Chloride secretion occurs predominantly in the crypt cells, but can occur from the surface epithelium as well. Chloride secretion is activated by cAMP-dependent stimulation of CFTR chloride channels. CFTR is the gene product that is affected by any of a number of mutations that cause cystic fibrosis. CFTR is the predominant Cl− channel in the colon and is responsible for both cAMP- and Ca2+mediated chloride secretion. CFTR is primarily activated by protein kinase A; however, other second messenger pathways are involved including protein kinase C, cGMP, and calmodulin-dependent kinase [2, 6]. Additional Cl− channels have been identified in the colonic mucosa that belong to a family of ClC Cl− channels. The ClC-2 channel is found in colonic epithelium and is regulated by changes in intracellular pH as well as cell volume. They have been localized at tight junction complexes in the crypts [2]. Lubiprostone accelerates colonic transport through the activation of ClC-2 channels on the apical membrane of epithelial cells [9, 10]. As mentioned above, bicarbonate is also secreted to the luminal side of the epithelium and is responsible for the slightly alkaline pH of the colonic lumen [2]. Secretion of electrolytes is often accompanied by secretion of macromolecules. Mucus is probably the most important of these macromolecules and this mucus creates a barrier between the colonic luminal contents and the epithelium [2]. Secreted mucus in the colon forms two distinct layers. The outer loose layer contains bacteria and lubricates feces and protects epithelial cells from abrasion and chemical insult. An inner layer is essentially sterile and is a dense gel that contains antimicrobial peptides, enzymes, and secretory immunoglobulin A (IgA) amongst other substances [3]. Mucus is secreted from goblet cells as well as crypt epi­ thelial cells. Cholinergic stimulation releases preformed mucus. Increased intracellular cAMP induces mucus synthesis. Prostaglandins stimulate mucus secretion from columnar epithelial cells [2].

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J.I.S. Bleier and K.B. Wilkins

Figure 2-4. Schematic representation of the components of the enteric nervous system. Courtesy of Robin Noel.

 egulation of Electrolyte and Water R Absorption and Secretion Under normal physiologic conditions, there is a net absorption of sodium chloride and water. Under pathologic conditions, active Cl− secretion predisposes to the development of ­diarrhea. Secretion and absorption are mediated by ­endocrine, paracrine, autocrine, immunologic, and neuronal input [2, 6]. The major neuronal input is via the myenteric (Auerbach’s) plexus and the submucosal (Meissner’s) plexus. These plexi innervate epithelial as well as vascular smooth muscle cells and regulate colonic blood flow, absorption, and secretion. Food substances, bile acids, and bacterial or viral toxins may act as secretagogues. Secretory hormones and neurotransmitters include vasoactive intestinal polypeptide (VIP), acetylcholine (ACh), histamine, secretin, and serotonin. Substances that inhibit secretion include growth hormone, neuropeptide Y, somatostatin, opiates, and norepinephrine [2]. There is also evidence to suggest that small gaseous molecules, gasotransmitters, also play a role in regulating colonic ion transport. Examples of gasotransmitters include nitric oxide, carbon monoxide, and hydrogen sulfide [6].

Colonic Innervation Nerves supplying the colon serve to control and modulate colonic motor function. These nerves have a multitude of functions including the following: (1) afferent input via ­chemoreceptors and mechanoreceptors, (2) efferent output to smooth muscles cells that either stimulate or inhibit

c­ ontraction by the release of neurotransmitters, (3) modulate the release of neurotransmitters through the release of neuromodulators, (4) control colonic sphincter activity for functions including defecation, and (5) generate signals for the initiation of propagating and nonpropagating motor complexes (see below) [11]. The nerves that control these functions are of both extrinsic and intrinsic origin. The extrinsic pathways originate from the central and autonomic (sympathetic and parasympathetic) nervous systems. Intrinsic innervation consists of the enteric nervous system [11, 12]. It is speculated that central control contributes minimally to baseline colonic tone except as it relates to defecation when voluntary relaxation of the external anal sphincter and contraction of abdominal musculature is required. It is unknown whether the central nervous system provides continuous input to colonic motor control [11]. Autonomic pathways run along parasympathetic and sympathetic chains. Each of these pathways include afferent (sensory) and efferent (motor) innervation. Vagal and pelvic nerves provide parasympathetic input to the colon. Vagal fibers reach the proximal colon along the posterior vagal trunk that follows the arterial blood supply along superior mesenteric arterial branches. The rectum and distal colon receives parasympathetic input from the sacral nerves (S2– S4) through the pelvic plexus. Parasympathetic stimulation stimulates motor activity of the circular and longitudinal muscle throughout the colon. Unlike vagal afferents, the pelvic afferents contain pain fibers and thus convey visceral sensory input (Figure 2-4). Acetylcholine is the major cholinergic parasympathetic neurotransmitter. Noncholinergic neurotransmitters may also play a role [11, 12].

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2.  Colonic Physiology

Sympathetic fibers originate from several sources i­ncluding the lumbar ventral roots (L2–L5), postganglionic hypogastric nerves, and the splanchnic nerves (T5–T12). The lumbar ventral nerve roots provide the main sympathetic supply to the colon. These nerves synapse on the inferior mesenteric ganglia. From there, the post-ganglionic nerves course along the inferior mesenteric artery to synapse on the enteric ganglia. The postganglionic hypogastric nerves also originate from the inferior mesenteric ganglia and then join the pelvic plexus. The hypogastric nerves primarily innervate the anal sphincters. The splanchnic nerves reach the proximal colon as they course along the blood supply. It is speculated that the lumbar nerves innervate the entire colon while the splanchnic nerves likely only innervate the proximal colon. The primary targets of the sympathetic efferent pathways include myenteric ganglia, submucosal ganglia, blood vessels, and sphincters. Sympathetic innervation is inhibitory to the myenteric ganglia and thus inhibits colonic contractions. However, sympathetic input to sphincter muscle is excitatory. Taken together, sympathetic input decreases peristalsis. Amongst numerous other substances, norepinephrine is a neurotransmitter that is known to exert inhibitory effects via a-2 adrenergic receptors in the myenteric plexus [13, 14]. While central and autonomic innervation is important, the intrinsic (enteric) nervous system is unique in that colon can continue to function even when these circuits have been interrupted. Specifically, the colon exhibits reflexes in the absence of extrinsic neural input. This is due to the complex system of 200–600 million ganglia that comprise the enteric nervous system. These ganglia arise from neural crest cells that colonize the gut during embryological development. The enteric nervous system consists of full reflex circuits comprising sensory neurons, interneurons, and motor neurons. This complex system is regulated by a multitude of neurotransmitters and neuromodulators and is responsible not only for controlling colonic motor activity, but also mucosal ion absorption and secretion and intestinal blood flow [3, 11, 12, 15]. Two major sets of ganglia are found in the colon. The myenteric or Auerbach’s plexus is located between the longitudinal and circular smooth muscle layers and plays a crucial role in colonic smooth muscle function. The submucosal or Meissner’s plexus regulates ion transport [3, 13–15]. The extreme importance of these two plexuses is clear in children with Hirschsprung’s disease in which the ganglia of the myenteric and submucosal plexuses are congenitally absent. The aganglionic segments do not relax and peristalsis is disturbed resulting in severe constipation [14]. There is also a mucosal abnormality predisposing to enterocolitis. Nearly 20 types of enteric neurons have been identified and every class of CNS neurotransmitters has been identified in the enteric nervous system. Besides neurotransmitters, other chemicals act in an endocrine or paracrine function to influence the enteric nervous system. While not totally inclusive,

substances identified as playing a role in the enteric nervous system include acetylcholine, norepinephrine, 5-hydroxy­ tryptamine (serotonin), dopamine, substance P, neurotensin, vasoactive intestinal peptide, somatostatin, prostaglandins, and neuropeptide Y [11, 12, 16]. Intrinsic primary afferent neurons (IPANs) are the neurons through which enteric reflexes are initiated. These were initially described as Type II neurons with long axonal processes extending to the mucosa and other neurons. However, it has become clear that other non-Type II neurons also play a crucial role in enteric sensation. Nonetheless, these IPANs function to sense changes in luminal chemistry and pressure as well as colonic muscular tone. IPANs are present in the myenteric and submucosal plexi [12, 14, 15]. While the IPANs monitor luminal stimuli, they need to do this transepithelially, since nerve fibers do not directly have contact with the colonic lumen. Therefore, sensory transducer cells in the epithelium are present to respond to mucosal changes. Enterochromaffin (EC) cells represent a type of this sensory transducer cell. EC cells contain large quantities of serotonin. Nearly 95% of serotonin is found in the gut and most of that is stored in the EC cells. When EC cells are stimulated, serotonin is secreted from the basolateral surface of the EC cells of the lamina propria. This is where the serotonin has access to nerve fibers. Serotonin can be excitatory or inhibitory depending on which type of serotonin receptor with which it interacts. Serotonin is not catabolized by enzymes, but is taken up by specific serotonin reuptake transporters (SERT) present in serotonergic neurons. While beyond the scope of this chapter, it is worth mentioning that in patients with irritable bowel syndrome, mucosal expression of SERT is reduced. The importance of serotonin in the enteric nervous system and the role it plays in irritable bowel syndrome has allowed the development of medications to reduce the symptoms of IBS [3, 12, 15]. The 5-HT3 antagonist, alosetron, has been approved for treatment of IBS-­associated diarrhea in women [10, 15]. On the other hand, the 5-HT4 agonist, tegaserod, was initially approved for the treatment of IBS-associated constipation. Tegaserod was withdrawn from the market by the FDA in 2007 because of concerns of potential adverse cardiac events [9, 12, 15].

Colonic Motility Basic colonic motility requirements include slow net caudal propulsion, extensive mixing of semisolid stool, and uniform exposure of luminal contents to the mucosal surface. The colon also needs to rapidly move stool caudally during mass movements. In addition, the colon must be able to store fecal material in the colon until defecation. As reviewed above, most colonic motility is involuntary and is primarily mediated by the enteric nervous system in association with autonomic parasympathetic and sympathetic input.

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Cellular Basis of Motility The muscular apparatus of the colon consists of two distinctive layers of smooth muscle cells including the circular and longitudinal layers. These smooth muscle cells are interconnected by gap junctions that allow electrical signals to spread in coordinated fashion. Very important to this function are the colonic pacemaker cells, also called the interstitial cells of Cajal. The ICC are cells of mesenchymal origin. The ICC generates electrical pacemaker activity that provides the smooth muscle with the mechanism to produce propulsive rhythmic activity. They also appear to serve as conduits for muscle innervation and may transmit sensory information. In colon biopsy specimens, ICC density is able to be measured by c-Kit immunohistochemistry. ICC occur in ­ the submucosa and myenteric borders [3, 17–20]. ICC of the submucosa (ICC-SM) generate electrical stimuli with an oscillatory pattern of 2–4 Hz. Coupling of the ICC-SM to smooth muscle cells triggers large, slow repetitive depolarizations of the smooth muscle referred to as slow waves. Higher frequency oscillations (17–18 Hz) are generated in the ICC of the myenteric border (ICC-MP), but the slow waves from the ICC-SM seem to predominate [17–19].

Motility Patterns and Measurement Intraluminal colonic motility measurements (manometry and barostat studies) have provided an understanding of colonic motility patterns. Colonic motor activity is not ­rhythmic, but is characterized by brief (phasic) and sustained (tonic) contractions. At least seven different patterns of human colonic phasic pressure activity have been identified. These include non-propagating and propagating pressure waves and contractions. Non-propagating pressure waves occur randomly for at least 30 s. Simultaneous pressure waves occur simultaneously at least 10 cm apart with an onset time of 0.5 cm/s [19, 21, 22]. Clear physiologic patterns of colonic motor activity are recognized. Phasic activity demonstrates diurnal variation with activity decreasing during sleep and increasing upon awakening. Phasic activity also increases within a few minutes after a meal and continues for up to 2.5 h depending on the nutrient composition and caloric content of the meal. High fat meals elicit more of a response than carbohydrate rich meals. At least 500 kcal needs to be ingested to predictably cause a colonic response to the meal. Finally, colonic instillation of bisacodyl or intravenous neostigmine induces HAPCs. Colonic tone can be measured with a barostat. In physiologic states, colonic tone increases in response to a meal [17, 21–23]. Altered colonic motility may be manifest as constipation. Patients with constipation can be evaluated with several modalities including radiopaque marker studies, radionuclide scintigraphy, magnetic resonance imaging, dynamic defecography, wireless motility capsule (smart pill®, Given Imaging) evaluation, and colonic manometry/barostat studies [17, 18, 22, 23]. While the details of these modalities are discussed in subsequent chapters, it is worth mentioning several common findings in patients with slow transit constipation. Patients with slow transit constipation have a reduced frequency of HAPCs. These patients also lack the normal phasic response that is elicited by the intake of a meal. The diurnal variation of colonic motor activity also may be abnormal in patients with slow transit constipation. Colonic bisacodyl administration also produces a blunted HAPC response in patients with slow transit constipation. A diminished increase in colonic tone following a meal has also been observed in slow transit constipation [21–24]. Loss and injury to the ICC has also been observed in patients with constipation [20]. Taken together, slow transit constipation may be associated with both myopathic and neuropathic etiologies.

Clinical Aspects of Colon Physiology Ultimately, the main goal of understanding the concepts behind colonic physiology is to be able to translate these into effective therapy for the problems that plague our patients. Subsequent chapters in the text deal more specifically with these issues, but to illustrate this concept, we can consider the use of sacral neuromodulation (SNM). This is not a new therapy; however, its FDA approval for the treatment of fecal incontinence has brought it into the spotlight more recently. In addition to its efficacy for fecal incontinence and its complex interaction with the pelvic floor, European data has also shown its efficacy for the treatment of colonic motility disorders, specifically chronic constipation as well as low anterior resection syndrome. The postulated effectors for its success are based on the known principles of colonic motility

2.  Colonic Physiology

i­ llustrated in this chapter. Dinning et al. performed an ­elegant study in which patients with slow-transit constipation were treated with SNM. A manometry catheter was positioned colonoscopically, with its tip fixed in the cecum. Electrodes were then placed in both the S2 and S3 foramina and stimulated. They found that stimulation to the S3 nerve root significantly increased pan-colonic antegrade propagating ­ sequences (PS), while stimulation at S2 significantly incre­ ased retrograde PSs. During a 3-week trial 75% of patients reported increase frequency of bowel movements and decre­ ased laxative use [25]. The true mechanism of SNM on the enteric nervous system is not known; however, it is hypothesized to affect autonomic innervation, largely through CNSmediated effects. The colorectum is a complex organ with multiple roles in human homeostasis. By increasing understanding of its anatomy and complex physiologic components, the colorectal surgeon can gain not only a better understanding of its normal role, but the etiology of derangement in pathophysiologic conditions, as well as an opportunity to develop new therapies based on its known functions. These examples are demonstrated with much greater detail throughout other sections of the text.

References 1. Szmulowicz U, Hull T. Colonic physiology. In: Beck DE, Roberts P, Saclarides T, Senagore A, Stamos M, Wexner SD, editors. The ASCRS textbook of colon and rectal surgery. 2nd ed. New York: Springer Science + Business media LLC; 2011. p. 23. 2. Kunzelmann K, Mall M. Electrolyte transport in the mammalian colon: mechanisms and implications for disease. Physiol Rev. 2002;82(1):245–89. 3. Sellers RS, Morton D. The colon: from banal to brilliant. Toxicol Pathol. 2014;42(1):67–81. 4. Fry R, Mahmoud N, Maron D, Bleier J. Chapter 52: Colon and rectum. In: Townsend C, Beauchamp R, Evers B, Mattox K, editors. Sabiston textbook of surgery. 19th ed. Philadelphia: Elsevier Saunders; 2012. p. 1294. 5. Booth RE, Johnson JP, Stockand JD. Aldosterone. Adv Physiol Educ. 2002;26(1–4):8–20. 6. Pouokam E, Steidle J, Diener M. Regulation of colonic ion transport by gasotransmitters. Biol Pharm Bull. 2011;34(6): 789–93. 7. Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011; 17(12):1519–28. 8. Leonel AJ, Alvarez-Leite JI. Butyrate: implications for intestinal function. Curr Opin Clin Nutr Metab Care. 2012;15(5):474–9.

35 9. Hussain ZH, Everhart K, Lacy BE. Treatment of chronic ­constipation: prescription medications and surgical therapies. Gastroenterol Hepatol. 2015;11(2):104. 10. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. 2015;313(9):949–58. 11. Sarna SK. Colonic motor activity. Surg Clin North Am. 1993;73(6):1201–23. 12. Furness JB, Callaghan BP, Rivera LR, Cho HJ. The enteric nervous system and gastrointestinal innervation: integrated local and central control. Adv Exp Med Biol. 2014;817:39–71. 13. Sarna SK. Physiology and pathophysiology of colonic motor activity (2). Dig Dis Sci. 1991;36(7):998–1018. 14. Furness JB. The enteric nervous system: normal functions and enteric neuropathies. Neurogastroenterol Motil. 2008;20 Suppl 1:32–8. 15. Gershon MD. Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastro­ enterol. 2005;39(5 Suppl 3):S184–93. 16. Straub RH, Wiest R, Strauch UG, Harle P, Scholmerich J. The role of the sympathetic nervous system in intestinal inflammation. Gut. 2006;55(11):1640–9. 17. Gudsoorkar VS, Quigley EM. Colorectal sensation and motility. Curr Opin Gastroenterol. 2014;30(1):75–83. 18. Quigley EM. What we have learned about colonic motility: ­normal and disturbed. Curr Opin Gastroenterol. 2010;26(1): 53–60. 19. Brookes SJ, Dinning PG, Gladman MA. Neuroanatomy and physiology of colorectal function and defaecation: from basic science to human clinical studies. Neurogastroenterol Motil. 2009;21 Suppl 2:9–19. 20. Huizinga JD, Chen JH. Interstitial cells of Cajal: update on basic and clinical science. Curr Gastroenterol Rep. 2014;16(1): 363. 21. Bassotti G, de Roberto G, Castellani D, Sediari L, Morelli A. Normal aspects of colorectal motility and abnormalities in slow transit constipation. World J Gastroenterol. 2005;11(18): 2691–6. 22. Camilleri M, Bharucha AE, di Lorenzo C, Hasler WL, Prather CM, Rao SS, et al. American Neurogastroenterology and Motility Society consensus statement on intraluminal measurement of gastrointestinal and colonic motility in clinical practice. Neurogastroenterol Motil. 2008;20(12):1269–82. 23. Dinning PG, Smith TK, Scott SM. Pathophysiology of colonic causes of chronic constipation. Neurogastroenterol Motil. 2009;21 Suppl 2:20–30. 24. Bassotti G, Crowell MD, Whitehead WE. Contractile activity of the human colon: lessons from 24 hour studies. Gut. 1993; 34(1):129–33. 25. Dinning PG, Fuentealba SE, Kennedy ML, Lubowski DZ, Cook IJ. Sacral nerve stimulation induces pan-colonic propagating pressure waves and increases defecation frequency in patients with slow-transit constipation. Colorectal Dis. 2007; 9(2):123–32.

3 Anal Physiology: The Physiology of Continence and Defecation Vitaliy Poylin and Thomas E. Cataldo

Abbreviations RAIR Rectoanal inhibitory reflex SNS Sacral nerve stimulation FI Fecal incontinence MR Magnetic resonance

Key Concepts • The innervation of the anal sphincter complex is a mixed sympathetic and parasympathetic crossed over system that provides redundant safeguards to continence. • Normal continence and defecation require intact sensation and motor control and reflexes to sense, retain, and voluntarily expect the rectal contents at a socially appropriate time and place. • The normal physiology of the anus can be disturbed in a variety of ways resulting in lack of control, inability to expel, or chronic pelvic pain. • The process of childbirth can contribute significantly to alteration in anorectal anatomy and physiology resulting in a variety of disorders of defecation and/or incontinence.

Introduction The physiology of the anus and its surrounding structures is in essence the physiology of continence and controlled defecation. This is a physiology of balance and continuous feedback and complex reflexes. Normal continence requires a balance between the pressure inside the rectum and the combined tone of the internal and external sphincters. Defecation and the controlled passage of gas or stool at socially Electronic supplementary material:  The online version of this chapter (doi:10.1007/978-3-319-25970-3_3) contains supplementary material, which is available to authorized users.

a­ ppropriate circumstances required very fine sensation and ability to discern the rectal contents. Defecation requires the ­balance to tip in favor of the rectal pressure and contraction with simultaneous coordinated relaxation of the pelvic floor and internal and external sphincters. Disturbance in any part of this complex balance can result in incontinence either through reduced anal tone, excess rectal contraction, reduced sensation, or the inability to differentiate the consistency of the rectal contents. Alternatively, disorders tipping in the opposite direction may result in inability to properly or completely empty the rectum. Additionally, more proximal conditions resulting in chronic diarrhea or constipation may tip the balance. And forces even higher can contribute to the behavioral and psychosocial aspects of ordered and disordered function of the rectum and anal canal. It is the patient and skilled practitioner who listens to what the patient can teach and tell about how and what they are doing combined with a good working knowledge of anorectal physiology that can effectively intervene in disorders of defecation.

Normal Anatomy and Physiology For a detailed discussion on the anal anatomy, see Chap. 1. Briefly, the musculature of the anus is made up of three ­concentric cylindrical structures. The internal sphincter is derived as an extension of the involuntary circular smooth muscle of the rectum. The longitudinal muscle is derived from the outer longitudinal smooth muscle of the rectum, and ultimately does extend into the anus and turns medially through the internal sphincter to comprise the muscles of Treitz that support the internal hemorrhoids. Lastly, the external sphincter is derived from the voluntary striated muscle of the pelvic floor. The internal sphincter begins as a condensation of the inner circular involuntary smooth muscle of the GI tract at the top of the surgical anal canal, as the top of the anorectal ring. It

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_3

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extends downward to just proximal to the end of the e­ xternal sphincter in the non-retracted or effaced state. The length of the normal internal sphincter can vary from under 2 to over 4 cm. In the unstimulated state, the internal sphincter is chronically contracting and contributes approximately 50–75 % of the resting tone of the anus. It appears as a 2–3-­ mm hypoechoic band on transanal ultrasound imaging [1]. The internal sphincter may not represent a perfect cylinder in all patients. Proximal anterior defects have been demonstrated in nulliparous women [2]. Length and bulk of the sphincter can be reduced if deprived of innervation or hormones in postmenopausal women (progesterone). The external sphincter is a cylinder of striated muscle that extends downward from the levator ani muscle to the distal anoderm. Like the internal sphincter, it exists in a chronically contracting state, but has the potential when stimulated under voluntary control, to more than double the tone of the anus above the resting state. It was initially considered to be divided into three separate segments, deep, superficial, and subcutaneous; this is no longer thought to be a meaningful distinction [3]. Between the internal and external sphincters is a layer of mixed smooth and striated muscle that is made up of an extension of the longitudinal outer muscle of the bowel and some striated extensions of the levator ani muscle. As it extends downward, some aspects of the muscle cross medially through the internal sphincter to contribute to the suspensory muscles that hold the hemorrhoid complex in place (Trietz’s muscle). Distally, the conjoined muscle extends to the anoderm and through the external sphincter radially to form the corrugator cutis ani [1, 4, 5].

V. Poylin and T.E. Cataldo

Normal Continence Rectal Capacity Normal continence first requires a location to temporarily hold and assess the contents and expel them under control. The rectum therefore needs both a baseline capacity and the compliance to expand and the force to expel. The empty rectum is a low pressure vessel with the capacity to receive stool from the sigmoid. It must have the capacity to expand significantly to accommodate stool under pressure. Patients with diminished rectal capacity will suffer from fecal frequency, urgency and frequently may contribute to ­ incontinence.

Pressure and Motility Baseline pressure in the rectum is low, about 5 mmHg with frequent low amplitude contractions every 6–12 s. Occasional high pressure waves up to 100 mmHg have been demonstrated. The anal canal shows overlapping of resting tone with small oscillations of pressure and frequency of 15 cycles/min and cm H2O. Pressure in the anal canal ranges 10–14 times that of the rectum. Motor activity is more frequent, and contractile waves are of higher amplitude in the rectum than in the sigmoid [6]. This reverse gradient provides a pressure barrier resisting forward motion of stool and may propel stool back into the sigmoid as part of delaying bowel movements when it is not convenient [7]. Slow waves are observed in the anal canal with increasing frequency distally. This gradient is thought to help maintain continence by propelling the contents back into the rectum and helps keep the canal empty.

Innervation of the Anus and Pelvic Floor The parasympathetic fibers to the rectum and anal canal emerge from the sacral foramina at the S2, 3, 4 levels. They join the sympathetic hypogastric nerves in the pelvic plexus. From there mixed postganglionic fibers extend to the lower rectum and anal canal. Thereby internal sphincter is innervated by L5–S4 mixed autonomic function in crossed fashion so that unilateral injury still results in preserved function. The external sphincter is similarly innervated from branches of S2–3 via the inferior rectal branch of the pudendal nerve and the perineal branch of S4. This nervous distribution also carries the nerves of sensation and contributes to the functional aspects of continence. The upper anal canal contains a high density of free and organized sensory nerve endings [1, 6, 7]. Organized nerve endings include Meisner’s corpuscles (touch), Krause’s bulbs (cold), Golgi-Mazzoni bodies (pressure), and genital corpuscles (friction).

Rectoanal Sensation and Sampling The rectum does not itself have receptors for proprioception. The conscious sensation of the need to defecate lives in the levators and the anal canal, hence the preserved sensation in patients who have had complete proctectomies and anal anastomoses. Distention of the rectum triggers contraction of the external anal sphincter and significant internal anal sphincter contraction. As first described by Gowers in 1877 [8] the rectoanal inhibitory reflex (RAIR) is thought to allow the highly innervated sensitive epithelial lining of the upper anal canal to sample the contents of the distal rectum to determine its quality and consistency. This allows the patient to accurately discern flatus from stool, and liquid stool from firm. Alterations in this mechanism, either through reduced sensation, or impaired sampling can result in incontinence either through overflow or inability to

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3.  Anal Physiology: The Physiology of Continence and Defecation

d­ iscern that defecation is occurring. Impaired anal sensation has been associated with childbirth, perineal descent, and mucosectomy [9–11].

Structural Considerations In addition to the baseline resultant tone provided by the anal sphincter complex and the puborectalis sling, the entire structure is held closed by the angulation created by the puborectalis in its chronically contracted unstimulated state. This angle between the axis of the anus and the axis of the rectum is between 80° and 90° and is responsible for the majority of gross fecal continence. It may increase normally above 90 while sitting and will extend beyond 110° during normal defecation. In cases of dysfunctional defecation where the puborectalis does not sufficiently relax the angle can be enhanced by squatting and flexing the hips to an angle of less than 90°. The flap valve theory advocated by Parks suggests the anterior rectal mucosa constitutes a flap that lies over the upper end of the anal canal. Increased inter abdominal pressure not associated with defecation increased the angulation and closes flap more firmly over the upper anal canal. The flap is opened when the perineum descends and the anorectal angle is straightened. The anterior mucosal flap certainly seems to be a component of the issue when patients suffer from obstructed defecation and have evidence of internal rectal prolapse.

Role of Hemorrhoids in Normal Continence It has also been postulated that the normal function of the hemorrhoids, in a non-pathologic state serve as an additional important component of normal continence. Stelzner referred to the hemorrhoids as the corpora cavernosum of the anus [12]. These vascular cushions have the ability to expand as needed to create a seal above the anus creating the fine tuning of continence. This concept is supported by the observation that after formal hemorrhoidectomy some patients experience minor alterations in continence.

Sensation and Innervation Within the pelvis, the innervation of the proximal anal canal descends from the rectum. The rectum has a mixed sympathetic and parasympathetic innervation derived from the hypogastric nerves and the sacral parasympathetic nerves through the pelvic plexi. Extrapelvic innervation comes to the anus from the pudendal nerve derived from S2 to S4 via the inferior rectal nerve and ultimately spreads around the anus from both sides entering at lateral to slightly anterior positions. There is known to be significant crossover innervation around the anus as a complete disruption of either pudendal nerve does not result in asymmetric sphincter ­atrophy or fecal incontinence.

Sensory innervation within the rectum is sensitive only to stretch, resulting in vague sensation to visceral pelvic pain. Distal rectal stretch or distention can result in significant parasympathetic stimulation of the vagus nerve, thereby resulting in bradycardia and hypotension. The lack of pain-­ sensitive innervation proximal to a short distance from the dentate line is what allows some hemorrhoid treatments to be performed with relatively limited discomfort, e.g., elastic band ligation, injection sclerotherapy, and stapled hemorrhoidopexy. Somatic sensory innervation begins in the anal transitional zone proximal to the dentate line for a short variable distance 0.3–1.5 cm [13]. Within this zone, there is a dense collection of nerve endings for pain, touch, pressure, and temperature. As such they are theorized to be an integral part of the sampling aspect of the continence mechanism [14]. These fibers are derived from the pudendal branches, and complete anesthesia to this area can be provided by bilateral anal nerve blockade.

Normal Defecation Normal defecation is a complicated mechanism that relies on a close interaction between the somatic and autonomic nervous system, which includes the conscious and unconscious control of both sensory input and muscle contraction. The process starts with stool arriving into the rectum and sampling as described above. If it is not an appropriate time for defecation, the anal sphincter will contract and rectum will start to distend [7]. This process continues with progressive distention of the rectum without a person’s full awareness; patients are often unaware that they have stool in the vault during rectal exam. Conscious sampling, however, is also present during this process (one can differentiate between gas and stool and allow gas to pass, even with full rectum). As the rectum continues to expand, a person becomes aware (with continuous sampling) There is an urge defecate that usually lasts for a few seconds and can be controlled by further contraction of external anal sphincter (efferent nerve endings end in lumbosacral spine which is under higher control, that allows conscious suppression of the urge) [15, 16]. When it becomes socially appropriate to proceed, the defecation process again relies on both conscious and unconscious response. The process starts with contraction of abdominal musculature (Valsalva), which is also associated with contraction of the sigmoid colon to move stool forward. Pelvic floor musculature on the other hand relaxes, which is a combination of relaxation of puborectalis (releases sling around anorectal junction) and relaxation of remaining levator muscle. This allows the pelvic floor to descend slightly and straighten the anorectal angle. The rectum itself starts to contract and both internal and external sphincters relax. Even if the sphincters are not completely relaxed, at this point pressure in the rectum exceeds pressure in the anal canal and defecation will occur. This process can also be aided by assuming the squatting position, which increases

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the intra-­ abdominal pressure and straightens the rectum ­further. If the conscious decision to defecate is made during sampling (rectum is contracting, internal sphincters already partially relaxed) allowing the external sphincters to relax, then defecation will occur [17–19]. Once begun a number of patterns can occur. There may be a single evacuation of the rectal contents accompanied by mass peristalsis of the left and sigmoid colon clearing the bowel in one continuous movement, or the passage of smaller volumes of stool individually over a short time requiring recurrent efforts and straining [20]. These two patterns and variations thereof are dictated by the habits of the patient and other factors including the overall consistency of the stool. If a large volume of stool is delivered quickly to the rectum, normal rectal compliance and accommodation may be insufficient. In this case the patient with normal sensation and function will have a sense of acute urgency and can forestall defecation for 40–60 s with the use of voluntary contraction of the external sphincter to allow accommodation or move to a socially appropriate location to evacuate. For obvious reasons, studying this process can be difficult, and thus our understanding of it relies on what is observed during testing (e.g., defecography—Video 3.1; and anal mano­ metric studies) [2, 6], patients with neurologic deficits ­(specifically spinal injuries) [21] and animal studies. Animal studies revealed the presence of different, more sensitive mechanoreceptors in the rectum, when compared to the colon that are most responsive to tension and rapid distention [22–24]. These tension mechanoreceptors respond to both rectal distension and muscle contraction consistent with ­ the observation that rectal filling sensation coincides with the period of raised rectal pressure during rectal distension [3–6].

 hysiology of Tibial Nerve and Sacral P Nerve Root Stimulation in Fecal Continence For many years it has been recognized that chronic electrical stimulation of nerves entering the pelvis has had effects of visceral function and activity. Unilateral stimulation of the S3 or S4 nerve as it exits the foramen has been used for ­urinary incontinence for over 30 years; meanwhile benefits for fecal incontinence have been recognized as well. Most recently, sacral nerve stimulation has shown encouraging results for idiopathic constipation as well [25–27]. The exact mechanism of how sacral nerve stimulation creates its effect remains unclear. The physiological control of defecation relies on the coordinated sensory and motor efforts of the colon, rectum, and anus. Current opinion is that disordered defecation is secondary to several disturbances of anorectal and colonic physiology and not purely a sphincter disturbance in patients with FI or colonic transit failure in constipation. It is therefore likely that the therapeutic effects

V. Poylin and T.E. Cataldo

of SNS are due not only to peripheral motor stimulation of the anal sphincter complex in patients with FI as was initially proposed, but instead due to changes in the motor and/or sensory function of the combined functional anorectal ­ unit. Such a hypothesis would explain the “paradox” of SNS effectiveness in both FI and chronic constipation, i.e., it is likely that SNS is effective in both conditions not due to paradoxical actions in each, but instead by improvement of common pathophysiologies. This hypothesis also explains why FI and disordered defecation so frequently coexist [28]. Similarly, intermittent stimulation of the posterior tibial nerve has a beneficial effect on fecal incontinence through a mechanism that is not fully understood [29]. In 2014, Carrington et al. performed an exhaustive review of the scientific literature regarding sacral and peripheral nerve stimulation for fecal incontinence and constipation [15]. To summarize their findings, SNS had no demonstrable effect of rectal compliance or motility. It did seem to reduce hypersensitivity in those with reduced capacity and hypersensitivity, while increasing sensitivity in those patients with reduced sensitivity. Additionally sacral nerve stimulation increases mucosal blood flow when on and returns to ­baseline when off. There are higher levels of the neuropeptide substance P identified in rectal biopsies of those undergoing stimulation, which reverses after it is discontinued. The exact importance or impact of these two phenomena has not been identified as yet. Forty studies have examined changes in anal sphincter function through the use of anorectal manometry. Direct comparison between studies is difficult, as equipment specifications, study protocol, and method of results reporting is extremely variable between centers. Fourteen studies reported a significant increase in voluntary anal squeeze, with eight of these also reporting an increase in resting pressure.

Spinal Cord Injuries and Defecation The most interesting and informative studies in normal and abnormal defecation are provided by patients with spinal cord injuries. However, it is important to remember that this is a very heterogeneous group of patients with degrees of injury that can vary significantly from patient to patient [7]. High spinal cord injuries (above T7) interrupt higher control and sensation of the abdominal and pelvic floor musculature as well as colon in rectum [12, 29, 30]. This combination allows for lower tone in the colon and rectum. The decrease in propulsive ability of the colon, the decrease in tone resulting in distention and slower transit through the colon explains the constipation that often accompanies high spinal cord injuries. These patients are often unable to generate adequate intra-abdominal pressure or take squatting position to aid defecation [11, 13, 31]. At the same time, there is an unopposed stimulation of the lower neurons that increase contraction and spasticity of the pelvic floor and external anal sphincters.

3.  Anal Physiology: The Physiology of Continence and Defecation

Sensation is often also impaired which can eliminate the ­normal urge to defecate. Interestingly, this often does not affect mechanoreceptors and some patients will report vague sensation of pressure that is then interpreted as a need to defecate [31–33]. As a result, these patients often have chronic constipation caused by both diminished sensation and inability to move stool forward [12, 13]. This is combined with pelvic floor dysfunction and the inability to identify the urge to defecate and an inability to relax the pelvic floor. They often rely on a strict bowel program, which is a combination of laxatives, rectal stimulation and manual disimpaction [11–13]. Rectal stimulation can allow some patents to have decreased anal sphincter pressure. They can also experience fecal incontinence as a result of overflow and overfill of the rectum and well as damage to sphincters from manual disimpaction [12–14, 34]. Patients with low spinal cord injuries such as Cauda Equina Syndrome often have impaired afferent fibers that results in loss of tone in the internal and external sphincter muscle as well as impaired sensation. This can result in significant incontinence since any generation of intra-­abdominal pressure may result in bowel movement [11–13].

Obstructed Defecation Obstructed defecation is a poorly understood group of disorders resulted from an alteration in sensation, muscle relaxation or both. In many patients with these problems, the exact cause is multifactorial and/or the inciting event is not easily identifiable [35]. It is possible that an abnormality in the sensory mechanism is the primary insult in a number of patients [36]. Normal sensation is an integral part of normal defecation. It allows for appropriate reflexes, mostly importantly the anal sampling RAIR. Some causes of abnormal sensation can be fairly evident in patients such as those with significant proctitis (infectious or inflammatory) or those after anorectal injury/surgery. In the absence of above, the etiology is less clear. Dysfunction may be associated with conscious/subconscious inhibition of the need to defecate during childhood [15, 16, 37, 38]. According to this theory, repeated delays in defecation result in altered sensation that eventually leads to dyscoordination between the anorectal and pelvic floor musculature. As this process continues, even though patient may continue to experience “normal” urge to defecate, changes in sensation cause an increase in stimulation of lower (lumbosacral) neuronal loop; the relaxing effects of the upper parts of the nervous system are insufficient to overpower the abnormal stimulation. Once this occurs, and pelvic floor musculature such as puborectalis and sphincter complex fail to relax appropriately, increasingly higher intra-abdominal pressure is needed to overpower the rectal/anal pressure to evacuate [39]. This failure can be associated with pain and a feeling of incomplete evacuation.

41

Independent of what part of normal defecation was affected first, over time there is probably significant damage to the sensory pathways including receptors, efferent nerves and muscles. With time, this process will also start affecting the structural integrity of the pelvic floor. Obstructed defe­ cation disorders include intussusception, rectocele, non-­ relaxing puborectalis/levator muscle spasm, dyssynergic puborectalis, as well as enterocele and rectal prolapse. Although causes of enterocele and rectal prolapse may be complex, these disorders in their pure form are mechanical obstructions to defecation and thus beyond the scope of this chapter. Here we describe a few pathological conditions that are more directly affected abnormalities in sensory-muscular neurological loop. Intussusception is mucosal descent causing blockage of the lower rectum/anal canal. It is possible that it is a primary process in some patients arising from redundancy of mucosa, possibly poor tone, and pelvic floor descent (either primary structural problems or as a result of childbirth and muscle/nerve damage in women). In most patients it is likely a secondary process resulting from increased pushing and decreased relaxation. Once developed, intussusception itself generates mechanical blockage to defecation and further attempts to generate more pressure to evacuate stool [17–19, 40]. Rectocele likely develops by a similar process. It is defined as greater than 2 cm of rectal wall out pouching or bowing anteriorly while straining. It can be accompanied by intussusception. Rectoceles are caused by abnormal relaxation of the pelvic floor/sphincter complex or structural defects in the rectal wall created during childbirth. As a result, when a patient attempts to evacuate, generated pressure delivers stool anteriorly towards the weakened portion of the wall that is not contracting appropriately. This generates a sensation of bulge and incomplete evacuation and can be at least in part relieved in women by pushing on the vagina in the initial stages of the disease (Figure 3-1; Video 3.2). However, a rectocele itself is a very common finding on the exam and only a small proportion of patients who have it will ever have symptoms. Most symptomatic patients likely have a combination of a weaker rectal wall as well as dyssynergy of the sphincters or puburectalis [15, 41]. Pelvic floor dyssynergy (pelvic outlet obstruction) results from a failure of the puborectalis and/or sphincter complex to relax. It can also be caused by an abnormal contraction during evacuation. As a result, when a patient tries to evacuate the anorectal angle may not increase or may even become sharper. A patient’s natural response is to generate higher pressures in which only further worsens the symptoms. Over time, these changes likely cause more damage to the musculature and nerves. Similar to the rest of the disorders in this group, rectal sensation is also impaired, but whether it is a result of long-term damage or from an inciting event is unclear [15, 16, 18].

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V. Poylin and T.E. Cataldo

 athophysiology of Obstetric-Related P Problems

Figure 3-1.  Defecography still image of a rectocele.

Functional Anorectal Pain Most causes of anorectal pain can be routinely ascribed to such common conditions as anal fissures, hemorrhoidal disease, or inflammatory bowel diseases (see Chap. 11). There is a small group of disorders, however, that seem to be related to more functional, rather than structural problems [42]. Levator ani syndrome (levator spasm, puborectalis syndrome) is often described as dull pain, high in the rectum that is often made worse with sitting. By definition, it should last more than 20 min at the time and other causes are excluded [43]. Etiology of this condition is unclear. Interestingly, even though episodes may be triggered by difficult defecation (along with emotional stress among other things) it is not always associated with difficulty evacuating. Similar to other functional disorders, it is possible that alternations in sensation, and perhaps behaviors (deferring defecation, damage with hard stool) could contribute to the development and propagation of this problem. In addition, it is thought that prolonged muscle contraction may result in compression of vasculature, which then leads to relative ischemia and an increase in anaerobic consumptions. That in turn can cause activation of nociceptors in the muscle (bradykinin, Substance P), and further decrease in relaxation with spasm and pain [15, 16, 22]. Proctalgia fugax is a sudden severe anal pain, lasting seconds to minutes, that disappears completely. The etiology is unknown, but it seems to be related to stress. It is associated in some patients with a thickened internal sphincter muscle. Some studies suggest smooth muscle contraction is responsible for this pain [15, 16, 44].

One of the worrisome potential sequelae of pregnancy and delivery is fecal incontinence. It can develop as a result of direct disruption of the anal sphincter, muscle, connective tissue or pudendal nerve injury [45]. During pregnancy, there is direct pressure on the pelvic floor as well as hormonal changes. Progesterone, released during pregnancy, acts by suppressing contraction of smooth muscle and prevents ­premature uterine contraction. This leads to decreased gut motility (that can contribute to constipation) and diminished tonic contraction of anal sphincters [25, 46]. Androgen, progesterone, and estrogen receptors are found in squamous ­epithelium of the anal canal, indirectly supporting possible effects of this hormone on the sphincters [47]. In addition, progesterone causes ligamentous laxity [48]. When combined with increased intra-abdominal pressure, these changes contribute to stretching of the pelvic floor musculature, widening of the levator hiatus, and potentially pudendal nerve injury. The pudendal nerve can be affected during pregnancy by stretching as well as traction injury during delivery as described below [49]. Pudendal nerve injury can affect both external sphincters by de-innervating them and causing muscle atrophy as well as by affecting sensory components and altering RAIR. Evidence of neuropathy in pelvic floor musculature has been found after delivery as well as in idiopathic FI and constipation. Labor further complicates issues of continence. Pushing during labor can significantly exacerbate the above problem [50]. It can be associated with further muscle stretching or even evulsion and pudendal nerve injury [25]. This explains why a longer second stage of labor (pushing) is associated with higher rates later in life. In addition, there is likely effects of traction injury (increased baby weight is associated with higher chances of immediate and long-term problems). Use of additional devices to aid labor such as forceps and vacuum is associated with increased incidence of FI [25, 51]. This is likely related to direct damage to the sphincters as well as traction injury. Tearing and episiotomy are additional risk factors for FI and related to direct damage to the sphincter complex. Cesarean section is associated with lower incidences of flatus and stool incontinence, but this difference is smaller when comparing emergent Cesarean sections and vaginal deliveries. Emergent cesarean are often initiated after failure of labor to progress following significant pushing [52]. Although many women experience immediate mild problems with incontinence to flatus or stool, most have enough reserves to compensate. Presence of symptoms after delivery is an additional risk factor for developing significant incontinence in the future when age further weakens already damages muscles and nerves.

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3.  Anal Physiology: The Physiology of Continence and Defecation

Urogynecological Considerations and Pelvic Pain With all its complexity, the pelvic floor is anatomically very small area. It includes pelvic musculature and their corresponding nerves responsible not only for maintenance of continence and normal defecation, but also normal urinary gynecologic function. Not surprisingly, although dysfunction in any single system is common, more than one system is frequently affected. For example, physiologic and muscular changes associated with pregnancy and labor which effects the posterior compartment often has similar effects on middle and anterior compartment structures as well. Uterine prolapse is more common in multiparous women, especially in complicated deliveries. Urinary problems including incontinence are also common [16, 25]. The mechanism for urinary issues is likely the same as in posterior compartment problems, which is a combination of hormonal effects as well as direct damage to the pelvic floor muscle, nerves, and sphincters. Widening of the levator hiatus has been shown to affect middle and anterior compartments as well as posterior one. This can result in uterine and bladder prolapse in addition to rectal prolapse, intussusception, and rectocele [21]. Pregnancy and delivery effects on anal sphincters can affect urinary sphincters as well. It is common for women presenting with urinary incontinence to report fecal incontinence as well [16, 25]. As a result, urogynecologists see and treat a number of patients with anorectal problems, especially since the treatments available are similar between specialties (e.g., pelvic floor physical therapy, sacral nerve stimulation). Pelvic floor prolapse problems, especially of the middle compartment, may ­contribute to obstructed defecation. For this reason care should be taken to obtain full history of pelvic floor problems. Otherwise one risks missing significant contributors to patients’ symptoms and may compromise success of treatment. Another common problem is pelvic pain, and women with these symptoms are often referred directly to gynecologists, although underlying cause could be levator spasm or pelvic floor dyssynergy [23]. These problems are also commonly treated by our urogynecology colleagues utilizing similar techniques including physical therapy and other pelvic floor relaxation techniques. Diagnostic techniques employed by urogynecologists to diagnose anterior pelvic problems are often the same (MR defecography and conventional cine defecography, anal manometry). As a result, when patients present with anorectal problems related to pelvic floor issues, one has to maintain vigilance in identifying related problems with anterior and middle compartment since they can affect overall symptom control as well as how these problems are ultimately addressed.

References 1. Jorge JMN, Habr-Gama A. Anatomy and embryology of the colon rectum and anus. In: Wolff BG, Fleshman JW, Beck DE, Pemberton JH, Wexner SD, editors. The ASCRS textbook of colon and rectal surgery. New York, NY: Springer; 2007. p. 1–11. 2. Bollard RC, Gardiner A, Lindow S, Phillips K, Duthie GS. Normal female anal sphincter: difficulties in interpretation explained. Dis Colon Rectum. 2002;45:171–5. 3. Gordon PH. Anatomy and physiology of the anorectum. In: Fazio VW, Church JM, Delaney CP, editors. Current therapy in colon and rectal surgery. 2nd ed. Philadelphia, PA: Elsevier Mosby; 2005. p. 1–4. 4. Milligan ETC, Morgan CN, Jones LE, Officer R. Surgical anatomy of the anal canal and the operative treatment of haemorrhoids. Dis Colon Rectum. 1985;28:620–8. 5. Morgan CN. The surgical anatomy of the anal canal and rectum. Postgrad Med J. 1936;12:287–314. 6. Taylor I, Duthie HL, Amallwwod R, et al. Large bowel myoelectrical activity in man. Gut. 1975;16:808–14. 7. Gordon PH. Anorectal anatomy and physiology. Gastroenterol Clin North Am. 2001;30:1–13. 8. Gowers WR. The automatic action of the sphincter ani. Proc R Soc Lond. 1877;26:77–84. 9. Cornes H, Bartolo DCC, Stirra T. Changes in anal canal sensation after childbirth. Br J Surg. 1991;78:74–7. 10. Miller R, Bartolo DCC, Cervero F, Mortenson NJ. Differences in anal sensation in continent and incontinent patients with perineal descent. Int J Colorectal Dis. 1989;4:45–9. 11. Keighley MRB. Abdominal mucosectomy reduces the i­ ncidence of soiling and sphincter damage after restorative proctocolectomy and J-pouch. Dis Colon Rectum. 1987;39:386–90. 12. Stelzner F. The morphological principles of anorectal continence. In: Rickham PP, Hecker WSH, Prevot J, editors. Anorectal malformations and associated diseases, Progress in pediatric ­surgery series, vol. 9. Munich: Urban & Schwarzberg; 1976. p. 1–6. 13. Kaiser AM, Ortega AE. Anorectal anatomy. Surg Clin North Am. 2002;82:1125–38. 14. Duthie HL, Gairns FW. Sensory nerve-endings and sensation in the anal region of man. Br J Surg. 1960;206:585–95. 15. Sangwan YP, Solla JA. Internal anal sphincter: advances and insights. Dis Colon Rectum. 1998;41:1297–311. 16. Palit S, Lunniss PJ, Scott SM. The physiology of human defecation. Dig Dis Sci. 2012;57:1445–64. 17. Bajwa A, Emmanuel A. The physiology of continence and evacuation. Best Pract Res Clin Gastroenterol. 2009;23: 477–85. 18. Brookes SJ, Dinning PG, Gladman MA. Neuroanatomy and physiology of colorectal function and defaecation: from basic science to human clinical studies. Neurogastroenterol Motil. 2009;21 Suppl 2:9–19. 19. Gurjar SV, Jones OM. Physiology: evacuation, pelvic floor and continence mechanisms. Surgery. 2011;29(8):358–61. 20. Lubowski DZ, Meagher AP, Smart AC, et al. Scintographic assessment of colonic function during defecation. Int J Colorectal Dis. 1995;10:91–3.

44 21. Brading AF, Ramalingam T. Mechanisms controlling normal defecation and the potential effects of spinal cord injury. In: Weaver LC, Polosa C, editors. Progress in brain research 2006; vol 152:p. 345-­358 (Chapter 23). 22. Broens PMA, Penninckx FM, Ochoa JB. Fecal continence revisited: the anal external sphincter continence reflex. Dis Colon Rectum. 2013;56:1273–81. 23. Lynn PA, Olsson C, Zagorodnyuk V, et al. Rectal intraganglionic laminar endings are transduction sites of extrinsic mechanoreceptors in the guinea pig rectum. Gastroenterology. 2003; 125:589–601. 24. Lynn PA, Blackshaw LA. In vitro recordings of afferent fibres with receptive fields in the serosa, muscle and mucosa of rat colon. J Physiol. 1999;518(Pt 1):271–82. 25. Tanagho EA, Schmidt RA. Electrical stimulation in the clinical management of the neurogenic bladder. J Urol. 1988;140: 1331–9. 26. Ganio E, Luc AR, Clerico G, Trompetto M. Sacral nerve stimulation for treatment of fecal incontinence: a novel approach for intra­ ctable fecal incontinence. Dis Colon Rectum. 2001;44:619–29. 27. Malouf AJ, Wiesel PH, Nicholls T, Nicholls RJ, Kamm MA. Sacral nerve stimulation for idiopathic slow transit constipation. Gastroenterol Clin North Am. 2001;118:4448–9. 28. Carrington EV et al. A systematic review of sacral nerve stimulation mechanisms in the treatment of fecal incontinence and constipation. Neurogastroenterol Motil. 2014;26(9):1222–37. 29. Thumas TO, Dudding TC, et al. A systemic review of posterior tibial nerve stimulation for faecal incontinence. Colorectal Dis. 2012;15:519–26. 30. Ebert E. Gastrointestinal involvement in spinal cord injury: a clinical perspective. J Gastrointestin Liver Dis. 2012;21(1): 75–82. 31. Lynch AC, Frizelle FA. Colorectal motility and defecation after spinal cord injury in humans. In: Weaver LC, Polosa C, editors. Progress in brain research 2006;vol 152:193–203 (Chapter 23). 32. Nout YS, Leedy GM, Beattie MS, Bresnahan JS. Alterations in eliminative and sexual reflexes after spinal cord injury: defecatory function and development of spasticity in pelvic floor musculature. In: Weaver LC, Polosa C, editors. Progress in brain research 2006;vol 152:359–273 (Chapter 23). 33. Preziosi G, Raptis DA, Raeburn A, Panicker J, Emmanuel A. Autonomic rectal dysfunction in patients with multiple sclerosis and bowel symptoms is secondary to spinal cord disease. Dis Colon Rectum. 2014;57:514–21. 34. Valle’s M, Mearin F. Pathophysiology of bowel dysfunction in patients with motor incomplete spinal cord injury: comparison with patients with motor complete spinal cord injury. Dis Colon Rectum. 2009;52:1589–97. 35. Bharucha AE, Rao SSC. An update on anorectal disorders for gastroenterologists. Gastroenterology. 2014;146:37–45. 36. Bharucha AE, Wald A, Enck P, Rao S. Functional anorectal ­disorders. Gastroenterology. 2006;130:1510–8.

V. Poylin and T.E. Cataldo 37. van Ginkel R, Reitsma JB, Buller HA, et al. Childhood ­constipation: longitudinal follow-up beyond puberty. Gastro­ enterology. 2003;125:67–72. 38. Rao SSC, Tuteja AK, Vellema T, et al. Dyssynergic defecation: demographics, symptoms, stool patterns and quality of life. J Clin Gastroenterol. 2004;38:680–5. 39. Rao SS, Welcher KD, Leistikow JS. Obstructive defecation: a failure of rectoanal coordination. Am J Gastroenterol. 1998;93: 1042–50. 40. Andromanakos N, Skandalakis P, Troupis T, Filippou D. Constipation of anorectal outlet obstruction: pathophysiology, evaluation and management. J Gastroenterol Hepatol. 2006;21: 638–46. 41. Felt-Bersma RJ, Tiersma ES, Cuesta MA. Rectal prolapse, rectal intussusception, rectocele, solitary rectal ulcer syndrome, and enterocele. Gastroenterol Clin North Am. 2008;37: 645–68. 42. Atkin GK, Suliman A, Vaizey CJ. Patient characteristics and treatment outcome in functional anorectal pain. Dis Colon Rectum. 2011;54:870–5. 43. Hull M, Cort MM. Evaluation of the levator ani and pelvic wall muscles in levator ani syndrome. Urol Nus. 2009; 29(4):225. 44. Eckardt VF, Dodt O, Kanzler G, Bernhard G. Anorectal function and morphology in patients with sporadic proctalgia fugax. Dis Colon Rectum. 2004;39:755–62. 45. Shin GH, Toto EL, Schey R. Pregnancy and postpartum bowel changes: constipation and fecal incontinence. Am J Gastroenterol. 2015;110:521–9. 46. Chiloiro M, Darconza G, Piccioli E, et al. Gastric emptying and orocecal transit time in pregnancy. J Gastroenterol. 2001;36: 538–43. 47. Oettling G, Franz HB. Mapping of androgen, estrogen and progesterone receptors in the anal continence organ. Eur J Obstet Gynecol Reprod Biol. 1998;77:785–95. 48. Shultz SJ, Wideman L, Montgomery MM, et al. Changes in serum collagen markers, IGF-I, and knee joint laxity across the menstrual cycle. J Orthop Res. 2012;30:1405–12. 49. Parks AG, Swash M. Denervation of the anal sphincter causing idiopathic anorectal incontinence. J R Coll Surg Edinb. 1979; 24:94–6. 50. Bharucha AE, Fletcher JG, Melton III LJ, et al. Obstetric trauma, pelvic floor injury and fecal incontinence: a populationbased case–control study. Am J Gastroenterol. 2012;107: 902–11. 51. Dudding TC, Vaizey CJ, Kamm MJ. Obstetric anal sphincter injury incidence, risk factors, and management. Ann Surg. 2008;247(2):224–37. 52. Pretlove SJ, Thompson PJ, Toozs-Hobson PM, et al. Does the mode of delivery predispose women to anal incontinence in the first year postpartum? A comparative systematic review. BJOG. 2008;115:421–34.

4 Endoscopy Kurt Davis and Michael A. Valente

Key Concepts • The endoscopic examination is critical for patients with colorectal complaints and is a key component of the complete colorectal examination. • The anoscopic examination is the best way to adequately evaluate the anoderm, dentate line and evaluate for internal and external hemorrhoids, and anal masses. • Multiple bowel preparation regimens exist, but regardless of which prep is chosen, splitting the timing into the half the day prior to and half the day of the procedure results in a better prep. • There is no ideal sedation medication, but the endoscopist must be familiar with the side effect profile of any medications being used and be prepared and comfortable with any reversal agents. • Adjunctive maneuvers employed with endoscopy serve as the markers between seasoned experts and novices: these include abdominal pressure, adjusting position, torqueing, and dithering. • PillCam endoscopy allows the clinician to evaluate the small bowel for occult gastrointestinal bleeding, insipient tumors, polyposis syndromes, or Crohn’s disease.

The Complete Anorectal Examination While performing any anorectal or endoscopic examination, an anxiety-free and modest environment must be created. Most patients will exhibit nervousness, and apprehension, which can cause anal or gluteal spasm that will preclude an accurate assessment. The examiner must reassure the patient and keep anxiety and embarrassment to a minimum. This can be accomplished by effective communication, keeping the patient covered as much as possible, keeping ancillary personnel in the room to a minimum and not rushing through the examination. Physicians should strive to actively communicate with the patient as the examination is progressing. Before a discussion on endoscopic techniques, a thorough understanding of the initial steps of the anorectal examination is compulsory for success and patient well-being and satisfaction. Before any instrument is inserted, a focused history must be obtained coupled with a local examination. The local examination is an important precursor to any endoscopic examination and consists of: proper patient positioning, visual inspection, and manual palpation of the anorectal region followed by the digital rectal examination. Once this stepwise examination is complete, then inspection of the colon, rectum, and anus can commence.

Introduction The endoscopic evaluation of the patient with colorectal complaints forms the keystone of the physical examination. It allows the physician to visually assess the entirety of the intestinal tract from the mouth to the anus and allows for the diagnosis, treatment, and monitoring of the effectiveness of any therapy. It is imperative for all physicians treating patients with colorectal diseases to be facile in the more common endoscopic diagnostic and therapeutic techniques.

Patient Position There are two positions that may be used for effective anorectal examination. The choice of position may depend on several variables including available equipment, patient age and comorbid status, and physician preference. Regardless of the position chosen, both the patient and the examiner must be comfortable in order to carry out an effective anorectal and endoscopic evaluation.

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_4

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K. Davis and M.A. Valente

Figure 4-1.  Prone jackknife position. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2015. All Rights Reserved.

Prone Jackknife

Left Lateral

The prone jackknife position (knee-chest), performed with the aid of a specialized proctoscopic table is commonly employed and allows for excellent visualization of the entire anus and perianal and perineal region, as well as the sacrococcygeal region. The patient kneels on the padded portion of the table and leans forward with their trunk and arms extended forward (Figure 4-1). The table is angled forward gradually so that the patient’s buttocks and perineum are superior, while the head and feet are inferior. This is a comfortable position for the examiner and also allows for easy insertion of the anoscope, proctoscope, or flexible sigmoidoscope. This position is well tolerated by most patients, but should be avoided in various situations, such as debilitated patients, recent abdominal surgery, cardiopulmonary issues, various arthritic/rheumatologic conditions, or late pregnancy.

The left lateral recumbent (Sims’) position is also widely used, especially if a specialty bed is not readily available (Figure 4-2). This position is very well tolerated and is well suited for elderly or debilitated patients. The patient lies on their left side and the thighs are flexed as to form a 90° angle with the trunk. It is imperative that the buttocks project slightly beyond the edge of the examining table. This position will allow for excellent visualization of the perianal and sacral regions, but the anterior perineum is often obscured and requires the retraction of the buttock by an assistant. Anoscopic or endoscopic evaluation is easily performed in this position.

Inspection and Palpation Proper stepwise visual inspection of the perineum, anal canal, rectum, and vagina should precede any other examination.

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4. Endoscopy

will elicit the anocutaneous reflex (anal wink), which is indicative of an intact pudendal nerve. Additionally, gentle spreading of the anus will help elicit an anal fissure or ulceration. Palpation of the gluteal region can help identify an abscess, external opening of a fistulous tract, or possibly a mass.

Digital Rectal Examination

Figure 4-2.  Left lateral (Sims’) position. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2015. All Rights Reserved.

Proper lighting is essential, and various light sources are commercially available, including overhead lights, gooseneck lamps, or headlamps. It should be noted that the “clockface” nomenclature is not recommended for localizing anorectal findings. This nomenclature is dependent upon the position of the patient, and hence different interpretations of the true location may differ from examiner to examiner. It is more proper to delineate anatomical location using the cardinal quadrants (i.e., left lateral, right anterior, right posterior). This is the practice most commonly employed by colorectal surgeons. An overall assessment of the shape of the buttock and inspection of the lower sacrococcygeal area is undertaken. This is followed by the gentle spreading of the buttocks to gain proper exposure. A great deal of information can be gained from visualization. The physician should examine for and document any scarring, fecal soiling, purulence, blood or mucous drainage, excoriations, erythema, anal sphincter shape, perineal body bulk, hemorrhoidal disease, skin tags, overt signs of inflammatory bowel disease, external fistulous openings, rectal prolapse, neoplasm, and any evidence of previous anorectal surgery. Next, the patient is asked to strain (Valsalva maneuver) to help determine and assess for perineal descent, uterine, vaginal, or bladder prolapse, or rectal prolapse. It should be noted that the best position to evaluate rectal prolapse is in the sitting position on the toilet or commode after an enema has been administered. Gentle and directed palpation of the anorectal region also gives the examiner a great detail of information. Gently touching the anal verge

The digital rectal examination (DRE) is simple and is typically well tolerated and should be performed before all endoscopy of the rectum and colon. A well-performed DRE will provide information regarding the contents and potential pathology of the anal canal, distal rectum, and adjacent organs. The DRE may also permit an assessment of the neurological function of the muscles of fecal continence. While the medical school maxim of the only patient not receiving a DRE is the one that lacks an anus is obviously excessive— there are relative contraindications to performing this portion of the exam. These include painful lesions such as an anal fissure, thrombosed external hemorrhoids, grade IV internal hemorrhoids, and neutropenic patients. The keys to a successful DRE can be summarized by simple rules: adequate lubrication, gentleness, and attention to detail [1]. It is important to minimize pain during DRE as this may affect patient cooperation during endoscopy. After proper communication with the patient, a well-­ lubricated index finger is placed across the anus to lubricate the general area. The fingertip is then gently inserted into the anal opening. Lubrication should be warmed if possible, and lidocaine jelly should also be available. If the patient’s response is an involuntary spasm of the internal sphincter, the examiner should withdraw their fingertip and gently try again. Ask the patient to bear down as to pass a stool. This maneuver will cause relaxation of the entire sphincter complex and should facilitate an easy digital insertion [2]. The finger should be gradually and slowly advanced. The distal rectum and anal canal along with surrounding structures should be investigated in an organized and stepwise fashion. Resting anal tone followed by squeeze tone should be assessed. Assessment should be made of the entire circumference of the lumen by gently sweeping around the entire anus and distal rectum. Anteriorly in a male, the prostate should be palpated and assessed for nodularity, hypertrophy and firmness. In the female, anteriorly palpate for a rectocele. The cervix and uterus can also be palpated. Posteriorly, the presence of a presacral (retrorectal) mass may be palpated. Bimanual examination may be necessary when examining a female patient in order to adequately examine the rectovaginal septum and associated adnexal structures. Redundant rectal mucosa may be palpated as well as a stricture or narrowing. Induration or a fibrous cord, representing an internal fistulous opening, may also be felt on DRE. Exclusion of any masses should be carefully performed. The patient should be asked to perform a Valsalva maneuver to potentially bring any lesions of the upper rectum or the rectosigmoid into the examiners reach. If a mass is palpated, its size, position,

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K. Davis and M.A. Valente

Anoscopy

Figure 4-3.  Various beveled anoscopes. From top to bottom: Large Hirschmann (short bevel); Buie-Hirschmann anoscope (long bevel); small (pediatric) Hirschmann anoscope.

characteristics (sessile, polypoid, ulcerated), mobility (mobile, tethered, fixed), and relationship to other structures (distance from the anal verge, distance for the anorectal ring) must be accurately recorded. The levator ani/puborectalis muscles can also be assessed on DRE with evaluation of both the strength and function of these muscles, along with any tenderness on direct palpation, indicating a possible pelvic pain disorder. When a patient with good sphincter function is asked to squeeze these muscles, the examiner’s finger will feel the muscle tighten and will have his finger pulled up into the rectum. Additionally, when the examiner pulls posteriorly on these muscles, the anal opening should gape and then return to normal, representing an intact reflex pathway to the thoracolumbar spinal cord.

Anoscopy/Proctoscopy The anorectal examination in most cases should be followed with some component of an endoscopic investigation to complete the workup. This may include anoscopy, proctoscopy, or flexible endoscopy. Anoscopy and proctoscopy are typically performed in the clinic setting without sedation or mechanical bowel preparation and are tolerated quite well by the patient. It should be noted that the term proctoscopy will be used as to describe the rigid scope implemented to evaluate the rectum and the distal sigmoid colon. Therefore, “rigid proctosigmoioscope” or “proctosigmoidoscopy” will be referred to as “rigid proctoscopy” or “proctoscopy.” Sigmoidoscopy refers to the use of the flexible sigmoidoscope.

Anoscopy is the examination of the anal canal and the distal rectum. Anoscopy offers the best way to adequately evaluate the anoderm, dentate line, internal and external hemorrhoids, papillae, fissures, anal masses, and distal rectal mucosa. The anoscope is a relatively simple instrument consisting of an obturator, the scope itself, and a light source. There exist several variations in type, size, and length of anoscopes available. Additionally, commercially available anoscopes include slotted or beveled styles, reusable or disposable, and lighted or unlighted. The particular type of instrument and light source used are based on individual preference, expense, and prior training (Figure 4-3). Regardless of the choice of instrument used, the examination is initiated only after a DRE has been performed (if a DRE is unable to be performed secondary to pain, spasm, or stenosis, an anoscopic exam should not be attempted). For most instances, cleansing of the anorectum with an enema is not warranted. The anoscope (with obturator in place) is liberally lubricated and gently and gradually advanced until the instrument is fully inserted. It is important to align the anoscope along the anterior–posterior axis of the anus. If unsuccessful due to patient intolerance, remove the scope, reapply lubrication and try again. After successful insertion, the obturator is removed and examination of the anorectum undertaken. The obturator should then be reinserted while the scope still in the anus, and the anoscope is gently rotated to examine a new area. The prone jackknife position offers good visualization and ease of insertion as well does the lateral position, however, an assistant must retract the buttock if the lateral position is utilized. During the examination, the patient is asked to strain while the anoscope is withdrawn to visualize any prolapsing anorectal mucosa or hemorrhoidal tissue. During the anoscopic examination, hemorrhoids may be banded or sclerosing agents injected and biopsies of any suspicious lesions may be obtained. Complications are rare, but may include occasional bleeding from hemorrhoids or inadvertently tearing the anoderm.

Proctoscopy Rigid proctoscopy is suitable to examine the rectum, and in some patients, the distal sigmoid colon may also be evaluated. Similar to the anoscope, the proctoscope consists of an obturator, the scope itself, and a light source. Illumination is supplied by a built-in light source and a lens is attached to the external orifice of the scope after the obturator is removed. The main difference between an anoscope is that a proctoscope needs to hold air so the rectum can be distended. This is achieved by having a bellows attached to the scope, which allows for insufflation of air to gain better visualization and negotiation of the scope proximally through the rectum. A suction device or cotton tipped swabs can be used to remove any endoluminal debris or fluid or to enhance visualization (Figure 4-4). Ideally, the patient should receive an enema preparation within 2 h of

4. Endoscopy

Figure 4-4. Proctoscopy suction catheter and long cotton-tipped applicators for clearing small amounts of fecal debris. The cottontipped swaps are also used for manipulating the rectal and anal mucosa during anoscopy and proctoscopy.

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Figure 4-6. Turell angulated biopsy forceps. A curved upper jaw allows for 360° rotation. A variety of jaw sizes and types are available.

Figure 4-7.  Rigid-wire (Frankfelt) snare. This snare allows for polypectomy or tumor debulking via the anoscope or proctoscope.

Figure 4-5. Proctoscopes. From top to bottom: large proctoscope, length 25 cm, diameter 19 mm; standard proctoscope, length 25 cm, diameter 15 mm; pediatric proctoscope, length 25 cm, diameter 11 mm.

the procedure in order to clear any stool, which may make passage of the scope and visualization difficult. Proctoscopes are available in three sizes, all 25 cm in length. Different luminal diameters include 11, 15, and 19 mm (Figure 4-5). The largest scope is suited best for polypectomy or biopsies in which electrocoagulation may be needed. In most patients, the 15 mm × 25 cm scope is ideal for a general inspection. There is also a disposable plastic, self-lighted proctoscope which is available for use. The procedure can be performed in either the prone jackknife or left lateral position as previously described. When properly performed, the patient feels little to no discomfort. Pain may occur with stretching of the rectosigmoid mesentery due to over insufflation of air or the scope hitting the rectal wall. An overzealous examiner trying to advance the scope too quickly or too proximal is the main cause of patient discomfort. Unfortunately, the art of using the rigid proctoscope has declined in recent years due to the ubiquity of flexible endoscopy. The proctoscope however, still has important indications, especially in the identification and precise localization of rectal lesions or in the evaluation of rectal bleeding. Contraindications are similar to anoscopy and include painful anorectal condition such as acute fissure, incarcerated hemorrhoids, recent anorectal surgery (1 cm Endoscopic dilatation Medications Medication Warfarin A-fib

↓ Risk procedures Diagnostic endoscopy Flexible sigmoidoscopy/colonoscopy ± biopsy Stent placement without dilation Risk

Medication instructions Hold 3–5 days prior Hold warfarin and start UFH or LMWH when INR ≤2.0 Hold warfarin and start UFH or LMWH when INR ≤2.0

↓ ↑

No medication adjustment necessary D/C 8 h prior to procedure Consider 1 mg/kg q 12 h

↓ ↑

No change necessary D/C 7–10 days prior to procedure, Restarting individualized consider continuing aspirin if on dual therapy If no preexisting bleeding disorder, no change necessary Unknown Medication not usually used in patients undergoing elective procedures. Consult with Prescribing Physician or Cardiology

A-fib w h/o embolic event Mechanical valvular heart disease Low molecular weight heparin (LMWH) Bridging LMWH: to replace Heparin Window D/C Warfarin 3–5 days prior to procedure Thienopyridines: clopidogrel/ticlopidine

Dipridamole

↓ ↑

GIIb/IIIa inhibitor

Medication restart

Restarting medication Individualized D/C as above

60

Patients who had an incomplete colonoscopy due to an unsatisfactory or poor prep must be re-educated on the preparation process, as above. A repeat colonoscopy in this situation is the most logical and effective approach [52, 53]. In patients whom the procedure was terminated secondary to tortuosity or pain, a repeat colonoscopy under alternate analgesia or a repeat colonoscopy with a more experienced endoscopist may be appropriate [49, 53]. Alternatively, CT colonoscopy (virtual colonoscopy) may also be performed with good success. It should be noted that any lesion >6 mm found on CT colonoscopy will require a standard colonoscopy as follow-up. As a final option, a double (air and ingested contrast) barium enema can be considered. Even though barium enema has been available for decades and is an accepted screening tool for colorectal carcinoma, a recent large population-based study showed a cancer miss rate of 22%, which makes this a very poor second test to either standard or CT colonoscopy [54]. In patients in whom the colonoscopy was incomplete secondary to stricture or an obstructing lesion, options include on-table colonoscopy at the time of resection, preoperative CT colonoscopy, or postoperative colonoscopy [49].

Procedure The Endoscopy Suite Unlike the flexible sigmoidoscopic examination that can be adequately performed in the office, a full colonoscopy typically requires a larger space with more equipment. The endoscopy suite should provide an adequate amount of space for the necessary endoscopic equipment and patient stretcher as well as allow adequate egress of staff and equipment. It is important that clear and unobstructed sight lines are maintained for all of the personnel in the endoscopy suite such that adequate visualization on the patient as well as any monitoring equipment is maintained at all times. It is dark in the endoscopy suite and the endoscopist is concentrating on the procedure therefore it is imperative to have a designated person, who’s primary responsibility is for monitoring the patient throughout the procedure. If sedation is to be used, as is most commonly performed in the USA, it is important that oxygen and routine EKG monitoring are performed. A consensus statement states that patients who are having their procedure performed under moderate or deep sedation “must have continuous monitoring before, during, and after the administration of sedatives.” Monitoring may detect early signs of patient distress, such as changes in cardiovascular or pulmonary parameters prior to any clinically significant compromise. Standard monitoring of sedated patients undergoing GI endoscopic procedures includes recording the heart rate, blood pressure, respiratory rate, and oxygen saturation. Although electronic monitoring equipment often facilitates assessment of patient status, it does not replace a well-trained and vigilant assistant [55].

K. Davis and M.A. Valente

Instruments As with flexible sigmoidoscopes above, there are numerous manufacturers of colonoscopes that typically vary from 130 to 168 cm in length. There are also pediatric colonoscopes that are smaller in diameter than the typical adult endoscope: 11.3 mm versus 12.8 mm. The basic colonoscope consists of a suction channel, an air/water channel, and fiber-optic bundles for light transmission, along with a biopsy port, which is connected into the suction channel (Figure 4-20a, b). Modern colonoscopes commonly possess variable stiffness controls that allow the endoscopist to vary the rigidity of the endoscope dependent on the clinical situation. It is hypothesized that this ability decreases the need for external over the tube stiffeners, and they have been proven to decrease procedure-­ related pain and the doses of sedative medications during colonoscopy [56].

Sedation There are numerous studies evaluating the optimal method in which to sedate the patient for colonoscopy procedures and there is ample dogma employed as well. As with a bowel prep, there is no perfect sedation regimen but the endoscopist must be familiar with the side effect profile of medications being used and be prepared and comfortable with any reversal agents. While there is literature demonstrating that colonoscopy can be performed adequately and safely on the un-sedated patient, the practice in the USA is rare. In one study, less than half of the endoscopists polled practiced unsedated colonoscopy, listing a lack of patient acceptance as the most common reason for not offering it [57]. In an evaluation of Canadian gastroenterologists and colon and rectal surgeons, the endoscopists reported using sedation for more than 90% of colonoscopies they performed. The most common sedation regimen was a combination of midazolam and fentanyl [58]. While the combination of a narcotic with a benzodiazepine remains popular for providing colonoscopy sedation, several alternate medications have been evaluated.

Nitrous Oxide Nitrous oxide is one medication that has been found effective in several studies to be effective for colonoscopic sedation. While some studies show that it is not an effective substitution for intravenous sedation and analgesics [59], there are several studies that show it to work well in that setting. In a review of seven randomized trials using nitrous oxide for colonoscopy, four showed that nitrous oxide is as good at controlling pain as conventional methods, while another showed that sedation was actually improved [60]. Despite this it is unlikely that Nitrous Oxide will become widely used in clinical practice.

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4. Endoscopy Figure 4-20. (a) End-on view of the endoscopic tip, showing suction/biopsy channel, air/water channel, lens, and light source. (b) Basic endoscope design. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2015. All Rights Reserved.

Ketamine

Propofol

Ketamine is another medication that has demonstrated beneficial in colonoscopy. In one study, the addition of lowdose ketamine to a standard sedation regimen resulted in more rapid and better quality of sedation with stable hemodynamic status, and similar recovery times [61]. Due to a lack of familiarity with the medication and concerns regarding central nervous system alteration this medication is also unlikely to receive widespread use for endoscopic sedation.

By far, the preponderance of the recent literature involving sedation for endoscopy involves the use of propofol, which has increased substantially among endoscopists [62]. In a Cochrane Review of the randomized controlled studies comparing propofol with standard sedation of a narcotic and benzodiazepine, the findings were that recovery and discharge times were shorter with the use of propofol. In addition, there was higher patient satisfaction with use of propofol. No difference in the procedure time, the cecal intubation rate

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or the incidence of complications was noted [63]. A later meta-­analysis confirmed these findings [64]. One criticism of the use of propofol is that an anesthesia provider is typically required to administer the agent—thereby increasing the cost associated with the procedure. It has been demonstrated that the medication can be delivered in a patient controlled setting [65] or by a nurse under the supervision of the endoscopist [66]. These methods are likely to remain in the minority, however, and the question remains unanswered in an era of cost containment whether the benefits listed above justify its use.

Colonoscopy Technique Colonoscopy is the most challenging endoscopic examination, and appropriate training, practice, attention to detail, and patience is needed in order to successfully complete this examination. The act of negotiating a 5–6 ft flexible tube through a tortuous colon painlessly and efficiently while performing detailed surveillance and therapeutic maneuvers is a difficult task. This section will describe successful navigation to the full extent of the colonoscopy relying on the principles mentioned prior.

Anal Intubation The well-lubricated colonoscope is inserted as previously described for sigmoidoscopy. The examiner must make sure that the scope is brought over to the patient straight without any twists or loops from the endoscopy tower.

The Rectum and Rectosigmoid Once the endoscope is placed into the anus, it is advanced into the rectum while insufflating an appropriate amount of air to distend the rectum. The distensibility of the rectum is an easy way to evaluate rectal compliance based on how easily and how much the rectum distends. Negotiating through the rectum is usually not difficult, but if difficulty is ­encountered going through the three valves of Houston (Figure 4-21), torque can be employed to reach the rectosigmoid. The rectosigmoid can pose extreme difficulty and is often one of the more challenging areas of the colonoscopy. There is often an acute angle at this junction from a redundant and floppy sigmoid colon. If the patient has undergone prior pelvic surgery, especially hysterectomy, the sigmoid may become fixed and adherent which makes negotiation of the turn difficult and often painful. In other patients (usually males) this turn is obtuse and very easy to advance. In situations where the turn is difficult, a combination of all the basic maneuvers discussed should be employed. The scope should be kept as straight as possible as a combination of short advancements—withdrawals with jiggle and a slight clockwise

Figure 4-21.  The first and second rectal valves of Houston. Note the large submucosal venous plexus.

torque (this torque may be considerable in certain individuals) should be employed to advance the scope into the sigmoid colon. This portion of the exam requires adequate patient sedation and relaxation. For the most acute angles, multiple small advancing steps toward getting the tip of the scope past the angle with tip deflection and torque are needed. Slide-by maneuvers should not be routinely performed. Once the scope advances into the sigmoid, tip deflection and some torque will help reduce any loops. If this is not possible, the scope can be carefully inserted farther into the sigmoid with the loop still in place as long as this does not cause too much patient discomfort. Once the descending colon comes into view, any loops should be reduced with withdrawal and torqueing maneuvers. This may require a substantial torque with the right hand and usually the endoscopist can feel the scope reduce and any patient discomfort or pain will usually abate at this time. It should be noted that successful completion of the procedure is quite low if the rectosigmoid loop is not reduced [67].

Sigmoid Colon The sigmoid colon is the most tortuous segment of the colon with associated high muscular tone, spasm, and a higher incidence of diverticulosis (Figure 4-22). The sigmoid colon is not fixed and can be very redundant and elongated. The sigmoid readily accepts the endoscope and a considerable length of scope can be inserted. All of these factors contribute to making this a difficult-to-navigate segment requiring insertion-pull back, jiggle, and a variable amount of torque (usually clockwise). These maneuvers will allow the sigmoid to “accordion” over the scope, which allows for efficient advancement and the prevention of loop formation. Diverticula, when present, can be of various sizes and the larger ones can be dangerous as they can be mistaken for the true bowel lumen. Careful navigation around a diverticula

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4. Endoscopy

Figure 4-22.  The sigmoid colon has variable degrees of tortuosity, spasm, diverticular disease, and muscular tone.

Figure 4-23.  Transverse colon: note the common triangular appearance of the lumen.

laden sigmoid requires patience and the pull back techniques in order to gain a broader view of the colon. Perforation of a diverticulum can occur if too forceful or blind advancement (slide-by) is incorporated.

changing patient position or externally splinting the sigmoid with abdominal pressure can achieve flexure passage as well. It should be noted that the straighter the sigmoid colon is, the easier the splenic flexure will be. A sigmoid loop can form during this portion of the exam if forward push is used to get past the flexure.

Sigmoid-Descending Junction The junction of the sigmoid and descending colon can be difficult if a sigmoid loop is present or has only been partially reduced. Keeping the scope straight and gently advancing and withdrawing 1–2 cm at a time usually works, as opposed to pushing through the loop which will undoubtedly cause pain. One can also attempt to apply abdominal pressure at this point or turn the patient position to supine (or lateral) in attempts to advance into the descending colon.

Descending Colon The descending colon is usually straighter and less muscular than the sigmoid colon. It should be noted that even though this segment of the colon is easier to advance, jiggle, torque, air suction, and push and pullback techniques should still be employed to pleat the colon over the scope.

Transverse Colon The transverse colon is characterized by the triangular appearance formed by the taenia coli (Figure 4-23). If no proximal loop has been formed, the scope will advance readily through this segment. If a loop is formed in the splenic flexure or the sigmoid, application of abdominal pressure at the sigmoid coupled with a strong torque (left or right) will usually reduce the loop and allow for a one-to-one advancement rather than a paradoxical advance. It should be remembered that torque, jiggle, and push-pull should be employed even when this segment is straight. One area of difficulty may be in the mid-transverse colon. The mid transverse colon may exhibit ptosis and descend down into the pelvis and could be fixed with adhesions, especially following pelvic surgery. Loops are commonly created during this part of the exam, and external pressure and changing the patient position to either right lateral or supine will help with advancement.

Splenic Flexure After advancing through the descending colon, the splenic flexure is the next obstacle. The splenic flexure is identified by the strong cardiac pulsations often seen and occasionally the blue shadow from the spleen itself. Often, this is a simple 90° turn that can be easily negotiated with some tip deflection and torque and other times, the splenic flexure may be a series of turns and twists in multiple planes. A difficult splenic flexure should be treated as already described using tip deflection, torque and push and pull techniques. Often,

Hepatic Flexure The hepatic flexure is often recognized by the large blue shadow from the liver (especially in thin patients) (Figure 4-24). As one advances through the transverse colon, the hepatic flexure comes into view, often with a variable amount of pooling liquid stool. If the flexure turn is very acute, the novice endoscopist often mistakes this “fools cecum” for the true one, believing that they are at the end of

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K. Davis and M.A. Valente

Figure 4-24.  Hepatic flexure: note the blue shadow from the liver. There is usually a sharp turn which can be quite difficult to negotiate.

the colon. As with any other turn or flexure, if the scope is straight, advancement will be easier than if a loop is formed proximally. Often, one can gently push through a loop and get into the ascending colon and then reduce the loop. At other times, the examiner may find it useful to use air suction and abdominal pressure techniques to negotiate this turn. Another technique previously mentioned, involves having the patient take a deep breath of air to push the diaphragm down, and thus, the scope down into the ascending colon. Figure 4-25.  Different appearance of the ileocecal valve. (a) Flat and subtle. (b) Polypoid and obvious.

Ascending Colon and Ileocecal Valve As the scope advances past the hepatic flexure into the ascending colon, prevention of a new loop is critical, as any proximal loop at this point will make further advancement of the scope extremely difficult. Pushing through a loop in the ascending colon is not as successful as it is on the left side of the colon since there are many bowel loops to accommodate before push pressure is transmitted to the end of the scope [67]. It can be very common to have the entire length of the scope inserted and there is still additional colon to traverse, due to inappropriate or minimal pleating techniques and the presence of loops. A change in patient position to either supine, right lateral, or prone coupled with the basic insertion techniques will prove to be extremely important in these situations and help advance the scope to the cecum. The ileocecal valve is a fold at the base of the ascending colon that may appear as an obvious polypoid-like yellowish mass or can be totally hidden (Figure 4-25a, b). When the valve is not easily recognizable, the presence of gas, stool, or bile flowing from it is helpful to aid in its identification.

Cecum The complete colonoscopic examination is ensured when the cecum has been reached. This blind sac is characterized by the “crow’s foot” which is made up of the muscular arrange-

ment of the colonic wall and the crescent or circular shaped appendicle orifice (Figure 4-26a, b). These landmarks are extremely important in quality assurance of a complete examination and photodocumentation is mandatory. Relying on trans-illumination of the scope through the abdominal wall in the right lower quadrant can be deceptive and is inadequate evidence of a complete examination. Careful and detailed examination of the entire cecum is important due to the fact that many cecal lesions, including serrated adenomas are flat or recessed and can be quite deceptive and easily missed with a casual examination.

Ileocecal Valve Intubation It is common for some endoscopists to routinely advance the endoscope into the terminal ileum. While it is considered a critical assessment when performing either an initial ­evaluation or follow-up for Crohn’s disease, or in a search for obscure bleeding, it is unclear the precise role of routine visualization of the terminal ileum on colonoscopy. It is a skill, and the ability of the endoscopist to perform the maneuver improves with practice. The technique involves first removing any loops from the colonoscope, as significant looping of the instrument make entering the ileum much more technically challenging. The edge of the ileocecal valve is hooked

65

4. Endoscopy

with the curved endoscope and the scope is then gently inserted into the ileum when the lumen is visualized (Figure 4-27). The intubation of the ileum confirms a complete colonoscopic evaluation and this confirmation can often be a frustrating endeavor for beginning endoscopist [68]. In an assessment of the ileal intubation learning curve, 50 procedures was the benchmark, but once learned could

be accomplished in most patients in less than 1 min [69]. The addition of routine ileoscopy to screening colonoscopy has been demonstrated to detect asymptomatic small bowel carcinoid tumors and has led some to argue that this should be considered part of the endoscopic examination [70]. A large study at the Mayo Clinic involving over 6000 patients however did not validate this. Terminal ileum intubation showed gross abnormalities in only 1% of the patients, and pathologic abnormalities were identified for only 0.3% of the patients. These authors concluded that intubation of the terminal ileum should not be a required part of screening colonoscopy [71].

Terminal Ileum If the endoscopist chooses to intubate the ileum, it is easily recognizable by its granular appearance and its increased motility (Figure 4-28). Quite often in younger patients, there will be innumerable lymphoid follicles that may resemble small polyps. The scope should be advanced as far as it is

Figure 4-26.  Reaching and proper identification of the cecum is compulsory for a complete examination. (a) Round appendiceal orifice with associated crow’s foot. (b) Crescent shaped appendiceal orifice.

Figure 4-28.  Terminal ileum: note the granular mucosa and the fine muscular folds.

Figure 4-27.  Intubation of the ileocecal valve: identification of the orifice, impacting the scope while giving air insufflation and then waiting for the bowel to relax before advancement into the

terminal ileum. Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography ©2015. All Rights Reserved.

66

comfortable and appropriate biopsies taken when needed. One should try to keep air insufflation to a minimum during this portion of the examination.

K. Davis and M.A. Valente

has primarily demonstrated an increase in the yield of small polyps in the general population, however. Due to this lack of clinical significance in the population as a whole, there is a questioning of the necessity for widespread application of the technique [82].

Alternate Techniques CO2 Insufflation

High Definition/NBI Endoscopy

Two alternatives to traditional air infusion colonoscopy are water-assisted colonoscopy and insufflation with Carbon Dioxide. Due to the fact that CO2 is more rapidly expelled from the colon than air, the hypothesis is that due to this rapid diffusion, there will be decreased pain associated with CO2 infusion compared to air. Some evaluations have been consistent with this [72] hypothesis, while others have not shared these findings [73]. Due to the paucity of literature documenting efficacy, the technique must be considered experimental at this point.

High definition endoscopes with wider angle viewing capability have the ability to increase the magnification and the visualization in endoscopy. High definition endoscopy has not proven superior in the ability to detect additional colon neoplasms, however [83]. Narrow Bandwidth Imaging (NBI) uses a filter to narrow the blue and green wave light and eliminates the red wavelength from standard white light. This leads to an accentuation of the microvasculature and improved visualization of pathology. The endoscopist is able to rapidly switch between white light and NBI views with the use of a foot pedal [84]. It has been noted in small studies that using NBI technology there is an increase in the number of adenomatous polyps detected [85]. In addition surface patterns differentiation between hyperplastic and adenomatous polyps is enhanced [86]. Due to this ability to better predict histology, NBI technology may play a role in the future resection and discarding of diminutive polyps, but it has not received widespread acceptance.

Water Insufflation The second method shows more promise. It involves the infusion of water without air and subsequent suctioning either during the insertion or withdrawal of the endoscope [74]. It has been demonstrated in limited studies that the use of waterassisted colonoscopy has a positive effect on patients, predominantly with lower levels of pain during the procedure [75, 76]. In addition, one study demonstrated that water immersion colonoscopy prevented loop formation in the sigmoid colon [77]. In a meta-analysis of nine studies, warm water infusion was demonstrated to be less painful than standard air insufflation, while reducing the need for sedation or analgesia during the procedure. There is a higher incomplete colonoscopy rate with this technique, however, and the endoscopist must consider this if considering employing this technique [78]. Interestingly when the methods of water insufflation and CO2 insufflation are compared to each other, there is no significant reduction in either moderate or severe pain with either technique, compared with patients receiving no sedation [79].

Chromocolonoscopy (Chromoendoscopy) Chromocolonoscopy involves the use of dye with spray catheters to spray coat the colonic mucosa in an attempt to increase the visualization of the mucosa. The dye enhances delineation, thereby aiding the endoscopist in differentiating between small structures, especially small and flat neoplastic lesions that are hard to recognize with traditional endoscopy. There has been some demonstrated benefit with this technology in high-risk populations such as those with inflammatory bowel disease or those with known genetic disorders [80, 81], due to the difficulty in differentiating abnormal from normal mucosa in some of these patients. The technology

Full Spectrum Endoscopy Full spectrum endoscopy uses three cameras, with the two additional cameras located adjacent to the scope’s tip. This allows simultaneous viewing of all three cameras, which the endoscopist has from three adjacently located monitors. This colonoscopy platform has been demonstrated to be feasible, usable, and safe [87]. Despite the impressive visualization that is gained from the additional cameras, at this point, there is no proven benefit regarding increased adenoma detection, making it only a viable alternative to traditional endoscope technology [88].

Retroflexion Many endoscopists routinely perform retroflexion, or the turning of the endoscope back upon itself in a U shape, in order to obtain a better view than with straight viewing. There is sparse data on either the benefits or the risks associated with the routine use of retroflexion of the endoscope in the rectum. There is one study that using the retroflexion technique with sigmoidoscopy increases adenoma detection [89]. Other studies cast some doubt on this. In one study of over 450 patients, in only 9 cases did the retroflex view identifiable pathology— predominantly hyperplastic polyps [90]. In another study of over 1500 patients, only 7 polyps were visualized solely by retroflexion. Six of these were hyperplastic and one was a

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4 mm sessile tubular adenoma [91]. More concerning than a low yield is a higher rectal perforation rate reported associated with the technique [92]. The procedure can undoubtedly be performed safely, and some experts tout that it provides valuable information and photodocumentation of benign disease at the rectal outlet such as hemorrhoids [93]. It is unclear if the limited data is worth any added risk. There is some data that retroflexion performed in the ascending colon, may offer benefit, however. One study evaluating routine retroflexion in the right colon showed that it could be safely achieved in the majority of patients undergoing screening colonoscopy [94]. In addition retroflexion identified additional polyps, predominantly adenomas, increasing the polyp yield as well as the adenoma detection rate in one study [95]. Due to the concerns regarding missed lesions in the right colon, retroflexion in patients with polyps identified on initial forward viewing should be considered.

Complications While the performance of colonoscopy is very safe with several million procedures performed every year with no untoward events—it is an invasive procedure and complications are possible. These should be discussed with the patient frankly and documented prior to the procedure. The complications can be broadly grouped into those relating directly form the procedure such as bleeding and perforation and those relating to the sedation involved with the procedure—primarily cardiac and pulmonary complications. The exact incidence of complications varies widely in the literature, from 4.0 for 10,000 colonoscopies [96] to 17.8 per 1000 procedures [97]. The incidence varies somewhat depending on what exactly is considered a complication, and looking only at serious complications, defined as those resulting in hospital admission within 30 days of the procedure occur with a rate of 1 per 1000 [98–100] to 5.0 per 1000 exams [101, 102].

colonoscopy and has been reported to occur in up to 16% of cases [104]. It is most likely not related to sedation, however, as the occurrence is unrelated to sedative medication administration and [105] it more likely results from the distension of the bowel or from a relative hypovolemic state resulting from the bowel prep. A vasovagal reaction is typically selflimited, but should be addressed by colonoscopic aspiration of air and/or reduction of loops. It typically requires no medical intervention other than monitoring and IV fluid administration. True cardiac arrhythmias are uncommon in association with colonoscopy. While there are reports of life threatening cardiac dysrhythmias during the procedure, these are primarily from case reports [106, 107]. Cardiac arrhythmias occur in approximately 2% of patients while undergoing endoscopic procedures [108] but the vast majority of these require no medical intervention [109]. The administration of sedative medications, particularly midazolam does cause transient hypotension in 20% of patients, with ST-segment depression in 7% of them [110]. It has also been noted in patients undergoing endoscopy that there is evidence of cardiac arrhythmias in 16%, with ischemic changes noted in 4% of those [108]. The clinical significance of these changes is unclear, however, as these are only electrocardiographic abnormalities. When comparing patients not having a colonoscopy, the incidence of myocardial infarction or stroke is similar to patients undergoing colonoscopy [111], implying that the procedure does not place the patient at increased risk for a cardiac event. In addition, it has been demonstrated that endoscopic procedures are safe and beneficial in patients after recent MI and should be performed if necessary in this patient population [112]. Colonoscopy in patients with a recent myocardial infarction is associated with a higher rate of minor, transient, and primarily cardiovascular complications compared with control patients but is infrequently associated with major complications [113].

Pulmonary Sedation Complications There are obviously risks associated with the administration of any medication, particularly sedative medications. The reason for the monitoring guidelines outlined above is to monitor for just these risks [103]. The primary concerns regarding the administration of sedation revolve around the cardiac and pulmonary complications associated with these medicines.

Vasovagal/Cardiac Arrhythmia A vasovagal reaction is a slowing of the heart rate, often accompanied by a drop in blood pressure. This is believed to reflect the stimulation of the vagus nerve. It is common during

The incidence of pulmonary complications is even less common than for cardiac events, and any evidence of pulmonary issues following a colonoscopy should prompt the endoscopist to consider the abdomen as the ultimate source. The majority of patients that are undergoing colonoscopy are older and patients over 80 have not surprisingly demonstrated higher rates of pulmonary complications [111]. There are reports of aspiration following the administration of sedative medications for colonoscopy [114], but this is a very uncommon event. In addition, there are also numerous reports of pneumothorax or pneumomediastinum, following a colonoscopy [115]. These events are most commonly related to an intra-abdominal perforation, however, and should prompt a quick investigation for that possibility [116].

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Procedural Complications Procedural complications such as bleeding, perforation, and post-polypectomy syndrome serve as the other broad classification of complications. There are reports of unusual occurrences such as colonoscopes becoming incarcerated in either inguinal or ventral hernias [117, 118], but these are extremely uncommon events and serve primarily to warn the practitioner that there is always something else that can go wrong with any procedure. All endoscopists should be aware of the more common risks associated with the endoscopy and attempt to mitigate them.

Splenic Injury The incidence of splenic injury in association with a colonoscopy is uncommon but is something that many endoscopists will encounter. A comprehensive literature search identified just over 100 patients worldwide with this complication [119]. It is likely that it is a much more common occurrence, however, as most of the cases in the literature are severe and the patients reported typically are managed with splenectomy [120]. There are likely many more cases that are not reported that are managed nonoperatively or even go unrecognized. It is believed that the etiology of this injury is from traction and subsequent tearing of the splenocolic ligament during the procedure, with subcapsular hematoma the most common injury pattern seen [121]. Splenic rupture at colonoscopy usually presents with abdominal pain developing within the first 24 h [122], although patients can present anywhere from a few hours to several days following the procedure [123]. Selection criteria for operative management may be extrapolated from those used for the management of traumatic splenic injury, but while there are reports of using splenic embolization [124], as mentioned above, the majority of patients in the literature have required splenectomy.

Perforation A perforation of the colon during a colonoscopy can be a devastating complication that can result in serious morbidity or mortality. While it is uncommon, endoscopists will likely encounter it at some point in their career. The exact incidence of perforation is difficult to precisely define, but it is much less than 1/1000 procedures, with rates of 0.012% [125] to 0.016% reported in large studies [126]. It is believed to be more common when the procedure is performed in a diseased colon such as in inflammatory bowel disease patients, but a large study of IBD patients showed a low perforation rate of 0.16% [127]. In most series attempting to examine the etiology of the complication, the incidence is as common when a biopsy is performed as from a diagnostic endoscopy alone [99, 128, 129]. There are three mechanisms believed to be responsible for colonoscopic perforation. The first is believed to be a mechanical perforation resulting from direct trauma from the

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colonoscope itself [130]. The most common anatomic site for perforation is the sigmoid colon, occurring in up to [131] 74% in some series [132]. This would be consistent with direct trauma, as the sigmoid is the narrowest and most tortuous section of the colon. The second mechanism is believed to be a result of barotrauma from air insufflation, and the ascending colon or cecum, which would be the most susceptible to this mechanism, is the second most common location for a perforation. However, one series that examined specifically patients that had a cecal perforation found that cecal pathology such as inflammation or ulceration contributed to the perforation in most of these patients [133]. The final etiology of perforation is believed to be from therapeutic procedures such as polypectomy or the dilation of strictures. The management depends not only on the condition of the patient, but on what the etiology of the perforation is felt to be. If the patient presents acutely and has peritonitis, the management is relatively clear and the patient warrants an emergent celiotomy. If the patient had a therapeutic endoscopy, and is clinically stable, then an attempt at nonoperative management is acceptable. The management with bowel rest and IV antibiotics has been demonstrated to be successful in 13/21 patients in one series of patients, all of whom had a perforation resulting from a therapeutic colonoscopy [134]. Perforations from a diagnostic colonoscopy are likely larger and are less successfully managed with nonoperative treatment [135]. The operative management of colonoscopic perforations has evolved as well. As in the trauma literature, if the patient requires surgical intervention, primary repair or resection with a primary anastomosis has proven to be an effective management strategy [132]. One emerging technology is the use of clips to manage a perforation that is either identified endoscopically or as prophylaxis when the endoscopist feels that the tissue has been thinned to the point that a perforation is likely. There are several case series reported in the literature with good results. A literature review of perforations managed with this technology show that if the clips were placed for a perforation during therapeutic colonoscopy it is successful in 69–93% of cases [136]. In one cohort of 27 patients with perforation from a therapeutic colonoscopy, the placement of clips resulted in successful nonoperative management in 25 of these patients [137]. In another review of 28 visible or suspected perforations, 13/19 evident and 8/9 suspected perforations underwent successful endoscopic closure with clips [138]. Clearly this technology has a place in the endoscopist’s armamentarium, but should also be employed with surgical consultation, so that early decisions regarding operative management can be made.

Post-polypectomy Syndrome Post-polypectomy syndrome is a spectrum of symptoms including abdominal pain, fever, leukocytosis, peritoneal tenderness, and guarding, following a colonoscopic polypectomy.

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It is believed to be the result of an electrocoagulation injury to the colonic wall, thereby creating a transmural burn with localized peritoneal inflammation, but without evidence of perforation. It has carried several other monikers as well, including post-polypectomy coagulation syndrome and transmural burn syndrome. Typically patients present several days following a colonoscopy with fever, localized abdominal pain, and leukocytosis and may have localized peritoneal signs on physical examination. The majority of these patients do not require surgical treatment and are usually adequately managed with bowel rest, intravenous hydration, broad-­spectrum parenteral antibiotics until symptoms resolution [139]. In one series, all patients were successfully managed medically without the need for surgery, with a median hospitalization of 5 days [140]. In an attempt to identify risk factors, one study found that polyp size greater than 2 cm and the presence of hypertension were the largest risk factors [141], but any patient who undergoes a polypectomy with cautery is at risk.

Bleeding Bleeding following a polypectomy is the most common serious complication following a colonoscopy and patients should be given specific written instructions regarding the actions they should take if it should occur. It is estimated that significant bleeding, requiring a patient to seek medical care, occurs in over [142] 3% of all colonoscopic polypectomies, with significant bleeding in over 1% [143–146]. While bleeding can happen immediately when the polyp is removed, this is typically dealt with by the endoscopist at the time of the procedure [147]. Clinically significant hemorrhage typically manifests itself 4–6 days following the procedure when there is clot dissolution [145]. There have been several studies attempting to elucidate those patients at higher risk for this complication. A difficult colonoscopy with procedural bleeding is one group of patients at higher risk [148]. Hypertension has also been noted to be not only a risk for bleeding, but for increasing the interval between the polypectomy and hemorrhage [149] In addition, patients on anticoagulation medications are not surprisingly at higher risk, with 34% of patients in one series having been recently restarted on their anticoagulant medications [145]. While there is an increased risk with anticoagulants, surprisingly, this risk is not seen with aspirin, NSAIDS, or other antiplatelet medications [150]. The size of the polyps excised is the most consistent predictor of delayed hemorrhage after a polypectomy [151]. It is much more common with larger polyps. Polyps greater than 2.0 cm diameter were noted to experience bleeding 3.8% of the time, compared to 0.3% when the polyps removed were smaller than 2 cm in one study [148]. In addition to the absolute size, the risk is noted to increase by 13% for every 1 mm increase in polyp diameter. While polyp size correlates with bleeding, the type of polyp either sessile or pedunculated has not been demonstrated to be a risk factor [152]. The location

of the polyp has, however, with polyps located in the right colon more susceptible to bleeding [153]. Microscopic examination of the vascular supply of resected polyps reveal that sessile and thick-stalked pedunculated polyps are supplied with more vessels than other polyps. Patients with polyps larger than 17 mm, pedunculated polyps with a stalk diameter >5 mm obviously place the patient at higher risk [154]. The endoscopist should obviously recognize those patients that are at highest risk for post-procedural bleeding and counsel them appropriately. The initial management of a patient with post-­polypectomy bleeding is identical to any other patient with intestinal bleeding. The patient should have coagulation parameters measured and resuscitation should be based upon hemodynamic parameters. There are no specific transfusion triggers with post-polypectomy bleeding, but advanced age is predictive of a patient receiving a transfusion [155]. Almost all patients can be managed with a repeat endoscopy and rarely are operative or other interventions necessary, although angiographic embolization has been demonstrated to be effective in the management of post-polypectomy bleeding [156]. The endoscopist should be familiar with advanced endoscopic hemostatic techniques for these procedures, or consult an experienced colleague. As with the management of perforation above, endoscopic clipping has been demonstrated beneficial in patients at increased risk for post-polypectomy hemorrhage. In one evaluation of polyps 2 cm or larger, there was a significantly decreased rate of post-procedure bleeding when the site was prophylactically clipped [157]. In addition, clipping has been shown to be beneficial in anticoagulated patients with lesions larger than 1 cm who were able to undergo successful polypectomy without interrupting the anticoagulation or antiplatelet medications [158].

Infectious Complications A word of caution should be made regarding the extremely rare infectious complications associated with endoscopy. Although it is uncommon, it is associated with sensationalistic press coverage when it does occur. The endoscopist should have a basic understanding of the process involved in the cleaning of the endoscopes and endoscopic equipment, as the majority of infectious complications result from breaches in cleaning procedures. In one survey of endoscopy centers, it was found that a significant number of centers did not conform to guidelines regarding the cleaning, processing and care of endoscopes [159]. A separate study found that several of the guidelines are inconsistent with one another, making it difficult to determine which guideline to follow [160]. Salmonella, Pseudomonas, and Mycobacterium species are the most commonly transmitted organisms associated with endoscopic equipment [161] and the ability of these bacteria to form biofilms on the inner channel surfaces is believed to contribute to their ability to survive the decon-

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tamination process [162]. There have recently been reports of Carbapenem-resistant organisms associated with endoscopy as well [163]. The endoscopist should always be vigilant regarding the equipment used and ensure that proper protocols are in place and are being followed.

Training and the Use of Simulation The training of medical personnel to safely and adequately perform colonoscopy is obviously critical. The criteria of what constitutes adequate training is controversial, however. Gastroenterologists perform the vast majority of colonoscopies and there are understandably differences in the manner in which different specialists, either gastroenterologists or surgeons educate and evaluate their trainees in performing procedures. Most of the literature on the topic involves gastroenterology fellows, and tends to focus on the number of procedures necessary in order to achieve competency. Surgical trainees obviously spend more time throughout their education learning procedural skills and it is doubtful that the two groups can be adequately compared regarding the speed or alacrity with which they learn procedures. It is unlikely that there will ever be a consensus on what constitutes adequate training. What is clear is that colonoscopy is a critical element in the treatment of the patient with colorectal disease and the colorectal surgeon must continue to be involved and have a voice in the education of the next generation of endoscopists. The ability to perform a colonoscopy is undoubtedly a skill and as with any skill, the ability to perform it improves with repetition. It is a point of contention exactly how many of these repetitions a trainee must perform. In evaluating first year gastroenterology fellows, it was found that the ability to intubate the cecum successfully improved and reached the requisite standard of competence—defined as completing the task greater than 90% of the time and within 20 min after 150 procedures had been performed [164]. When comparing first and third year gastroenterology fellows, it was found that competence improved throughout training but an independent completion rate of 90% was not obtained until after 500 colonoscopies were performed [165]. As with the ability to technically perform the procedure, quality metrics improve with experience as well. In one study, the adenoma detection rate (ADR) increased by year of training [166]. Another study however showed that from the beginning of their education, trainees were able to provide high-quality investigations, again using ADR as the quality indicator benchmark [167]. In one of the few comparisons between gastroenterology and surgery trainees, there was a disparity in endoscopic performance between trainees favoring the gastroenterology trainees [168]. A different study showed that following the use of endoscopy simulation surgery residents were capable of performing colonoscopy equivalent to their gastroenterology counterparts using quality metrics as the benchmark [169].

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Simulation The practice of endoscopy lends itself well to simulation, yet it has not been fully embraced. While surgical simulation is difficult to portray, basic endoscopy skills are well illustrated. Due to the myriad of surgical procedures that are performed and the manner in which they are performed, it is difficult to incorporate surgical simulation into the educational curriculum. Endoscopy, lends itself much better to simulation. The improvement of trainees using simulation is most noticeable during the beginning of their endoscopic experience [170]. Following a 6-h colonoscopy simulation, trainees were noted to significantly outperform those who did not have the training but these advantages are negligible after approximately 30 procedures on patients [171]. Despite this reported advantage, the technology has not received widespread adoption in gastroenterology training. In a survey of active gastroenterology fellows, they noted that while half of the programs have endoscopic simulators, only 15% are required to use them prior to performing endoscopy on patients [172]. In a review of program directors, this was confirmed with 15% requiring their fellows to use simulation prior to clinical cases, with only one program having a minimum number of hours required in simulation training. The majority of the program directors felt that there is a need for endoscopic simulator training [173]. The reasons for a lack of embracing simulation are unclear. An attractive method to increase the quality of colonoscopy performance and to increase the skill levels of trainees without excessive numbers of procedures is the incorporation of endoscopy simulation into the curriculum of training programs that train endoscopists.

Documentation and Quality Documentation After completion of the procedure it is important to adequately document any findings as well as any adjunctive procedures that were performed at the time. It is imperative to photodocument any lesions or areas that were biopsied, as well as the endoscopists interpretation of these lesions. An attempt to place the location anatomically should be made, as the distance of the inserted colonoscopy can vary greatly ­depending upon looping and can vary depending on whether the measurement was taken on insertion or while the endoscope was being withdrawn. In addition, if any lesion was biopsied, or if a polyp was excised, the note should document whether the excision was complete or whether there was grossly abnormal tissue remaining. A Multi-Society Task Force on Colorectal Cancer developed a consensus-based set of data points that reflected what should be included in any colonoscopy report (Table 4-3) [174].

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4. Endoscopy Table 4-3.  Recommended elements in standard colonoscopy report Documentation of informed consent Facility where endoscopy performed Patient demographics and history Age/sex Receiving anticoagulation: if yes, document management plan Need for antibiotic prophylaxis: if yes, document reason and management plan Assessment of patient risk and comorbidity ASA classification Indication(s) for procedure  Procedure: technical description    Procedure date and time    Procedure performed with additional qualifiers (CPT codes, polypectomy, etc.)    Sedation: medications given and by the type of provider responsible    Level of sedation (conscious, deep, general anesthesia)    Extent of examination by anatomic segment: cecum, ascending colon, etc.    If cecum is not reached, provide reason    Method of documentation: i.e., photo of ileocecal valve and/or appendiceal orifice    Time of examination: scope was inserted, withdrawal started, when withdrawn from patient    Retroflexion in rectum (yes/no)    Bowel prep: type of preparation, quality, adequate or inadequate to detect polyps >5 mm    Technical performance: not technically difficult or examination difficult    Patient discomfort/looping/need for special maneuvers including turning patient    Type of instrument used: model and instrument number Colonoscopic findings  Colonic masses or polyp(s)    Anatomic location: length/size (mm)    Descriptors: pedunculated/sessile/flat/obstructive (% of lumen reduced)/ulcerated    Biopsy obtained: hot/cold or snare/tattoo (if performed)    Fulguration or ablation with cautery    Completely removed (yes/no)/retrieved (yes/no)/sent to pathology (yes/no)  Mucosal abnormality    Suspected diagnosis: ulcerative colitis, Crohn’s, ischemia, infection    Anatomic location/extent/pathology obtained (yes/no)  Other findings Diverticulosis/arteriovenous malformations/hemorrhoids Assessment  Follow-up plan    Immediate follow-up/further tests, referrals/medication changes    Follow-up appointments and recommendation for follow-up colonoscopy and tests    Documentation of communication directly to the patient and referring physician  Pathology    Pathology results reviewed, communicated with referring provider with recommendation for follow-up and communicated with patient Adapted from Lieberman D, Nadel M et al. Standardized colonoscopy reporting and data system: report of the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. Gastrointest Endosc 2007 May;65(6):757–66 (17)

There are numerous commercially available software programs that allow rapid and accurate documentation and these guidelines will look familiar to any provider who has utilized these systems. Unfortunately, the very ease of these programs and their check-box design allow trainees or busy professionals to perform documentation that is inadequate. In one study involving both community hospitals and academic centers several deficiencies in reporting were identified. For example, bowel preparation quality was reported in only 20%, but

more concerning, the description of polyp appearance was present in only in 34% of notes [175]. In another study, photodocumentation was often missing and the size and morphology of polyps was present in only slightly more than 60% of cases [176]. Other studies show a consistent lack of documenting the quality of the bowel preparation, lack of documentation of the cecal landmarks as well as poor procedural interpretation [177, 178]. Clearly physicians who perform these procedures must not only ensure that the

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procedure is done well and safely, but that it is properly documented and these findings are relayed to the patient and any other treating physicians.

Quality There is increasing attention to quantifiable measures of quality in medicine, and colonoscopy lends itself well to metric analysis and therefore there has been a great deal of attention paid to these performance measures [179]. Almost 14 million colonoscopies are performed annually in the USA and there is understandably a great deal of attention paid to quality associated with the procedure. The five most frequently cited quality measures are cecal intubation rate, adherence to recommended screening and surveillance interval, adenoma detection rate, quality of bowel preparation, and colonoscopy withdrawal time [180]. While some of these elements are addressed elsewhere in this text, is imperative that surgeons remain involved in these discussions and the continuing quest for quality improvement for our profession and for our patients.

PillCam Endoscopy The advent of PillCam endoscopy (PCE) has revolutionized the evaluation of the small intestine. It allows the clinician to evaluate this portion of the intestine that was previously relegated to inaccurate or uncomfortable studies such as small bowel radiographic series or enteroclysis. The procedure is most commonly used in patients with occult gastrointestinal bleeding or in the search for other small bowel pathology, such as insipient tumors, polyposis syndromes, or Crohn’s disease [181]. It typically is performed after an upper and lower endoscopic examination has already been completed; however, it can complement the latter as well, as in at least one study 28% of abnormalities identified on PCE were within the area normally covered by an endoscopic exam [182]. The use of PillCam endoscopy is easy to perform and learn and is a natural adjunct in the endoscopists’ armamentarium. Capsule endoscopy does not require a bowel preparation, but most patients are instructed to remain either NPO or on a clear liquid diet for 10–12 h prior to the procedure. The patient swallows the disposable capsule, which then transmits images wirelessly to a recorder, and the clinician can review the images at a time when it is convenient to spend the 15–60 min, on average, for image viewing and documentation [183]. PillCam endoscopy has been demonstrated to play a significant role in Crohn’s disease, where the small intestine is difficult to visualize radiographically. While there are concerns for evaluating patients with stricturing Crohn’s disease, as the capsule can be retained at the location of a stricture [184, 185], this is typically less of a concern for a surgeon contemplating operative management and can serve as a

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marker of stricture location enabling the procedure to be performed with minimally invasive techniques. PCE has resulted in medication changes in up to 60% of patients in some studies and [186] has proven superior to other imaging modalities in identifying obscure sources of intestinal bleeding and is beneficial in the localization of small bowel neoplasms [187, 188]. In addition, there is data that PCE may play a role in screening for colonic neoplasm, or in the evaluation of large intestinal inflammatory bowel disease. It is clear that the uses for this technology will only expand and physicians who treat intestinal disease will have to be familiar with the technology [189].

Summary The endoscopic evaluation of the patient with colorectal complaints is essential in both the diagnosis and management of the patient. It allows the physician to visually assess the entirety of the intestinal tract and should not be thought of as a separate entity, but as an adjunct in the examination of the colorectal patient. These techniques should be familiar to the colorectal surgeon, and surgeons should continue to play a role in the testing, training, and advancement of endoscopic techniques and technology.

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K. Davis and M.A. Valente associated bowel perforation? Surg Endosc. 2010;24(5): 1177–85. 139. Kim HW. What is different between postpolypectomy fever and postpolypectomy coagulation syndrome? Clin Endosc. 2014;47(3):205–6. 140. Cha JM, Lim KS, Lee SH, et al. Clinical outcomes and risk factors of post-polypectomy coagulation syndrome: a multicenter, retrospective, case-control study. Endoscopy. 2013; 45(3):202–7. 141. Lee SH, Kim KJ, Yang DH, et al. Postpolypectomy fever, a rare adverse event of polypectomy: nested case-control study. Clin Endosc. 2014;47(3):236–41. 142. Rabeneck L, Paszat LF, Hilsden RJ, et al. Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology. 2008;135:1899–906. 143. Waye JD. Management of complications of colonoscopic polypectomy. Gastroenterologist. 1993;1(2):158–64. 144. Rosen L, Bub DS, Reed JF, Nastasee SA. Hemorrhage following colonoscopic polypectomy. Dis Colon Rectum. 1993; 36(12):1126–31. 145. Sawhney MS, Salfiti N, Nelson DB, et al. Risk factors for severe delayed postpolypectomy bleeding. Endoscopy. 2008;40(2):115–9. 146. Heldwein W, Dollhopf M, Rösch T, et al. The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies. Endoscopy. 2005;37:1116–22. 147. Kim HS, Kim TI, Kim WH, et al. Risk factors for immediate postpolypectomy bleeding of the colon: a multicenter study. Am J Gastroenterol. 2006;101(6):1333–41. 148. Wu XR, Church JM, Jarrar A, et al. Risk factors for delayed postpolypectomy bleeding: how to minimize your patients’ risk. Int J Colorectal Dis. 2013;28(8):1127–34. 149. Watabe H, Yamaji Y, Okamoto M, et al. Risk assessment for delayed hemorrhagic complication of colonic polypectomy: polyp-related factors and patient related factors. Gastrointest Endosc. 2006;64:73–8. 150. Hui AJ, Wong RM, Ching JY, et al. Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases. Gastrointest Endosc. 2004;59:44–8. 151. Moon HS, Park SW, Kim DH, et al. Only the size of resected polyps is an independent risk factor for delayed postpolypectomy hemorrhage: a 10-year single-center case-control study. Ann Coloproctol. 2014;30(4):182–5. 152. Buddingh KT, Herngreen T, Haringsma J, et al. Location in the right hemi-colon is an independent risk factor for delayed post-­ polypectomy hemorrhage: a multi-center case-control study. Am J Gastroenterol. 2011;106(6):1119–24. 153. Choung BS, Kim SH, Ahn DS, et al. Incidence and risk factors of delayed postpolypectomy bleeding: a retrospective cohort study. J Clin Gastroenterol. 2014;48(9):784–9. 154. Dobrowolski S, Dobosz M, Babicki A, et al. Blood supply of colorectal polyps correlates with risk of bleeding after colonoscopic polypectomy. Gastrointest Endosc. 2006;63(7):1004–9. 155. Sorbi D, Norton I, Conio M, et al. Postpolypectomy lower GI bleeding: descriptive analysis. Gastrointest Endosc. 2000;51: 690–6. 156. Rossetti A, Buchs NC, Breguet R, et al. Transarterial embolization in acute colonic bleeding: review of 11 years of experience and long-term results. Int J Colorectal Dis. 2012;28:777–82.

4. Endoscopy 157. Liaquat H, Rohn E, Rex DK. Prophylactic clip closure reduced the risk of delayed postpolypectomy hemorrhage: experience in 277 clipped large sessile or flat colorectal lesions and 247 control lesions. Gastrointest Endosc. 2013;77(3):401–7. 158. Katsinelos P, Fasoulas K, Chatzimavroudis G, et al. Prophylactic clip application before endoscopic resection of large pedunculated colorectal polyps in patients receiving anticoagulation or antiplatelet medications. Surg Laparosc Endosc Percutan Tech. 2012;22(5):e254–8. 159. Cheung RJ, Ortiz D, DiMarino AJ. GI endoscopic reprocessing practices in the United States. Gastrointest Endosc. 1999; 50(3):362–8. 160. Muscarella LF. Inconsistencies in endoscope-reprocessing and infection-control guidelines: the importance of endoscope drying. Am J Gastroenterol. 2006;101(9):2147–54. 161. Spach DH, Silverstein FE, Stamm WE. Transmission of infection by gastrointestinal endoscopy and bronchoscopy. Ann Intern Med. 1993;118(2):117–28. 162. Kovaleva J, Peters FT, van der Mei HC, Degener JE. Transmission of infection by flexible gastrointestinal endoscopy and bronchoscopy. Clin Microbiol Rev. 2013;26(2):231–54. 163. Kola A, Piening B, Pape UF, et al. An outbreak of carbapenem-­ resistant OXA-48—producing Klebsiella pneumonia associated to duodenoscopy. Antimicrob Resist Infect Control. 2015;4:8. 164. Lee SH, Chung IK, Kim SJ, et al. An adequate level of training for technical competence in screening and diagnostic colonoscopy: a prospective multicenter evaluation of the learning curve. Gastrointest Endosc. 2008;67(4):683–9. 165. Spier BJ, Benson M, Pfau PR, et al. Colonoscopy training in gastroenterology fellowships: determining competence. Gastrointest Endosc. 2010;71(2):319–24. 166. Peters SL, Hasan AG, Jacobson NB, Austin GL. Level of fellowship training increases adenoma detection rates. Clin Gastroenterol Hepatol. 2010;8(5):439–42. 167. Klare P, Ascher S, Wagenpfeil S, et al. Trainee colonoscopists fulfil quality standards for the detection of adenomatous polyps. BMC Med Educ. 2015;15(1):312. 168. Leyden JE, Doherty GA, Hanley A, et al. Quality of colonoscopy performance among gastroenterology and surgical trainees: a need for common training standards for all trainees? Endoscopy. 2011;43(11):935–40. 169. Williams MR, Crossett JR, Cleveland EM, et al. Equivalence in colonoscopy results between gastroenterologists and general surgery residents following an endoscopy simulation curriculum. J Surg Educ. 2015;72(4):654–7. 170. Cohen J, Cohen SA, Vora KC, et al. Multicenter, randomized, controlled trial of virtual-reality simulator training in acquisition of competency in colonoscopy. Gastrointest Endosc. 2006;64:361–8. 171. Sedlack RE, Kolars JC. Computer simulator training enhances the competency of gastroenterology fellows at colonoscopy: results of a pilot study. Am J Gastroenterol. 2004;99:33–7. 172. Jirapinyo P, Imaeda AB, Thompson CC. Endoscopic training in gastroenterology fellowship: adherence to core curriculum guidelines. Surg Endosc. 2015;24:4110–4.

77 173. Jirapinyo P, Thompson CC. Current status of endoscopic simulation in gastroenterology fellowship training programs. Surg Endosc. 2015;29(7):1913–9. 174. Lieberman D, Nadel M, Smith RA, et al. Standardized colonoscopy reporting and data system: report of the Quality Assurance Task Group of the National Colorectal Cancer Roundtable. Gastrointest Endosc. 2007;65(6):757–66. 175. Singh H, Kaita L, Taylor G, et al. Practice and documentation of performance of colonoscopy in a central Canadian health region. Can J Gastroenterol Hepatol. 2014;28(4):185–90. 176. Beaulieu D, Barkun A, Martel M. Quality audit of colonoscopy reports amongst patients screened or surveilled for colorectal neoplasia. World J Gastroenterol. 2012;18(27):3551–7. 177. Robertson DJ, Lawrence LB, Shaheen NJ, et al. Quality of colonoscopy reporting: a process of care study. Am J Gastroenterol. 2002;97(10):2651–6. 178. De Jonge V, Sint Nicolaas J, Cahen DL, et al. Quality evaluation of colonoscopy reporting and colonoscopy performance in daily clinical practice. Gastrointest Endosc. 2012;75(1):98–106. 179. Bourikas LA, Tsiamoulos ZP, Haycock A, et al. How we can measure quality in colonoscopy? World J Gastrointest Endosc. 2013;5(10):468–75. 180. Ketwaroo GA, Sawhney MS. Quality measures and quality improvements in colonoscopy. Curr Opin Gastroenterol. 2015; 31(1):56–61. 181. Hale MF, Sidhu R, McAlindon ME. Capsule endoscopy: current practice and future directions. World J Gastroenterol. 2014;20(24):7752–9. 182. Hoedemaker RA, Westerhof J, Weersma RK, et al. Non-small-­ bowel abnormalities identified during small bowel capsule endoscopy. World J Gastroenterol. 2014;20(14):4025–9. 183. Goenka MK, Majumder S, Goenka U. Capsule endoscopy: present status and future expectation. World J Gastroenterol. 2014;20(29):10024–37. 184. O’Donnell S, Qasim A, Ryan BM, et al. The role of capsule endoscopy in small bowel Crohn’s disease. J Crohns Colitis. 2009;3(4):282–6. 185. Long MD, Barnes E, Isaacs K, et al. Impact of capsule endoscopy on management of inflammatory bowel disease: a single tertiary care center experience. Inflamm Bowel Dis. 2011; 17(9):1855–62. 186. Dionisio PM, Gurudu SR, Leighton JA, et al. Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn’s disease: a meta-­analysis. Am J Gastroenterol. 2010;105(6):1240–8. 187. Triester SL, Leighton JA, Leontiadis GI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol. 2005;100(11):2407–18. 188. Zagorowicz ES, Pietrzak AM, Wronska E, et al. Small bowel tumors detected and missed during capsule endoscopy: single center experience. World J Gastroenterol. 2013;19(47): 9043–8. 189. Van Gossum A. Wireless capsule endoscopy of the large intestine: a review with future projections. Curr Opin Gastroenterol. 2014;30(5):472–6.

5

Endoscopic Management of Polyps, Polypectomy, and Combined Endoscopic and Laparoscopic Surgery Kelly A. Garrett and Sang W. Lee

Key Concepts • Colonoscopic polypectomy is the treatment of choice for diagnosing and removing most colon polyps. • Operator variability influences the quality of colonoscopy for both detection and resection. • Multiple questions remain about best practice techniques for colonoscopic polypectomy. • EMR of colorectal lesions is safe and effective but results in piecemeal resection that may prevent accurate histological diagnosis. Colonoscopy surveillance is required to assess for and manage local recurrence of neoplasia. • ESD is able to resect superficial lesions en bloc regardless of tumor size, location, and fibrosis. These advantages come at a cost of an increased risk of perforation, bleeding, and a longer procedure time as compared with EMR. • Combined endo-laparoscopic surgery is an adjunct to endoscopic polypectomy that may help to avoid colectomy.

Introduction It is estimated that 93,090 new cases of colon cancer will be diagnosed in the year 2015 with almost 50,000 estimated deaths due to colon cancer [1]. Although colon cancer is still the third most common cause of cancer related mortality in the USA, there has been a steady decline in the colorectal cancer incidence since the mid-1980s which is partially attributed to the introduction of colorectal cancer screening [2]. There has even been a more rapid decline in recent years (4% or greater per year from 2008 to 2011) which may be multifactorial but likely reflects the increased use of screening colonoscopy. Among adults aged 50–75 years, colonoscopy use increased from 19.1% in 2000 to 54.5% in 2013 [3]. Electronic supplementary material: The online version of this chapter (doi:10.1007/978-3-319-25970-3_5) contains supplementary material, which is available to authorized users.

Recently published data of the long-term follow-up from patients enrolled in the National Polyp Study provides evidence that colonoscopic removal of adenomatous polyps reduces colon cancer incidence and related mortality [4]. Colonoscopic polypectomy is the treatment of choice for diagnosing and removing most colon polyps. In the past decade, polypectomy technique, instrumentation, and evolution of endoscopy skills have improved polyp detection rates and the ability to remove polyps. Even so, large polyps or polyps in an anatomically difficult location can be challenging to remove endoscopically. Traditionally the most common recommendation for these patients has been to undergo a colon resection. Although the laparoscopic approach has reduced the morbidity of an abdominal operation, it still poses potential morbidities related to bowel resection. A combined approach using both laparoscopy and colonoscopy has more recently been described as an alternative to bowel resection in select patients with polyps that cannot be removed endoscopically. This chapter addresses endoscopic polypectomy—basic and advanced techniques and combined endoscopic endo-laparoscopic techniques.

Identification of Polyps Although there is little dispute about the impact of colonoscopy, there remains marked variability in the quality of colonoscopy. Indicators of quality colonoscopy include cecal intubation, withdrawal time, and polyp detection rate [5]. The need for cecal intubation is based on the persistent finding that a substantial fraction of colorectal neoplasms are located in the proximal colon including the cecum. Low cecal intubation rates have been associated with higher rates of interval proximal colon cancers [6]. Colonoscopy studies in screening patients in the USA have reported cecal intubation rates of 97% or higher [7, 8]. As the detection of neoplastic lesions is the primary goal of most colonoscopic examinations, careful inspection of the mucosa is essential. In 2002,

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_5

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the US Multi-Society Task Force on Colorectal Cancer recommended a withdrawal time (defined as the time from cecal intubation to the time the colonoscope is withdrawn out of the anus) of at least 6 min as an indicator of quality colonoscopy [9]. In 2006, Barclay et al. found a correlation between longer withdrawal time and an increased rate in the detection of adenomas [10]. There have been variations in the adenoma detection rates (ADR) and for this reason, targets for ADR have been recommended. The American Society for Gastrointestinal Endoscopy (ASGE) and the American College of Gastroenterology (ACG) recommends a minimum target for overall ADR of at least 25% based on the observation that higher ADRs were associated with a reduced risk of both proximal and distal cancer [11, 12].

Criteria for Polypectomy Polyps occur in all parts of the colon. It is the current practice, that when polyps are detected that they should be removed as any adenomatous tissue visualized should be assumed to carry some malignant potential [13, 14]. It is widely accepted that more than 95% of colorectal cancers arise from adenomatous polyps [15, 16]. This adenoma-carcinoma sequence is well described and is often an indolent process that takes many years. Polyps are characterized by their size and morphology (pedunculated or sessile), which are two important features that may predict underlying malignancy and should guide how polyps are managed. As defined by the US National Polyp Study, an advanced adenoma is one that is ≥ 1 cm in size or contains high grade dysplasia or appreciable villous tissue. When screening colonoscopy is performed in average-risk, asymptomatic individuals over the age of 50, the prevalence of advanced adenomas ranges from 6 to 9% [7]. It is accepted that removal of large adenomas is advisable to prevent progression to colorectal cancer. The malignant potential of adenomas 12 lymph nodes harvested when tattooing had taken place [19, 20]. An alternative to marking with tattoo is deployment of endoscopic metal clips followed by immediate plain radiograph. The colon outline is frequently visible due to retained air from colonoscopy. CT can also be obtained within a few days; the clips are usually retained and the tumor site can be clearly localized. Another strategy is to perform intraoperative colonoscopy to localize a small tumor. This can be performed immediately prior to operation or after exploration of the abdomen. The use of carbon dioxide as an insufflation gas is preferred, in order to limit bowel dilatation. If colonoscopy cannot be completed preoperatively, then a suitable radiographic study, such as CT colonography or contrast enema, should be considered or intraoperative colonoscopy performed via the colon proximal to the tumor. For cases of obstructing cancers that preclude adequate endoscopic or radiographic assessment preoperatively, intraoperative colonic lavage and colonoscopy should be considered. If this is not possible, the proximal colon should be palpated intraoperatively, and if no obvious lesions are detected, a full colonoscopy should be performed when safe to do so after surgery [4].

Carcinoembryonic Antigen Preoperative evaluation should also include routine laboratory studies, including a complete blood count (CBC) with focus on anemia that may need to be corrected before surgery. Another important test is the serum CEA level, which has been shown to provide some prognostic information [21]. CEA is a glycoprotein primarily involved in intercellular adhesion [22]. It is produced by columnar and goblet cells and can be found in normal colonic mucosa. Additionally, it can be found in low levels in the circulation of healthy individuals, but it is overexpressed in a variety of cancers, including colorectal cancer. Elevated serum levels may be identified in heavy smokers and in benign conditions such as pancreatitis and inflammatory bowel disease as well as malignancies outside of the gastrointestinal tract [22]; therefore, CEA is not a sensitive or specific screening tool for colorectal cancer [3, 23]. However, it is an important tool in CRC surveillance after surgical resection since its elevation may be the first indication of locally recurrent or metastatic disease [24]. Patients with preoperative serum CEA >5 ng/mL have a worse prognosis, stage for stage, than those with lower levels. Elevated preoperative CEA levels have been shown to be associated with poorer survival and increased recurrence in several studies; however, contradictory studies do exist [23, 25–29]. Therefore, there is currently insufficient evidence to support the use of elevated preoperative serum CEA levels as an absolute indication for adjuvant chemotherapy [4, 28].

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Current American Society of Clinical Oncology (ASCO) guidelines recommend that serum CEA levels be obtained preoperatively in patients with demonstrated colorectal cancer for posttreatment follow-up and assessment of prognosis. Elevated preoperative CEA levels that do not normalize following surgical resection imply the presence of persistent disease. Furthermore, serial testing of CEA levels should be performed for 5 years for patients with stage II and III disease in those eligible for surgery or chemotherapy if metastatic disease is discovered. Rising CEA levels after surgical resection imply recurrent disease and should prompt consideration of radiologic and endoscopic evaluation to look for treatable disease [28].

Radiographic Evaluation Preoperative radiographic imaging is fundamental for initial staging of newly diagnosed or recurrent colon cancers [4]. Computed tomography (CT) scans are the most widely used studies in this setting as they provide valuable preoperative information about liver or lung metastasis and are cost effective. This test should be done with both oral and intravenous contrast if there is no contraindication (anaphylaxis to contrast or renal insufficiency) to maximize accuracy of visualization of the abdominal viscera as well as highlight vascular structures and better determine the relationships between lymphatics, ureters, and vessels [30]. Additionally, cross-­ sectional imaging also facilitates more precise tumor location and delineates the extent of any extracolonic invasion of adjacent organs or the abdominal wall, all of which are important for operative planning [31]. In these cases, the appropriate consulting services can be mobilized if necessary for en bloc resections. CT scan has a sensitivity ranging from 75–90 % for detecting distant metastasis; however, the ability to accurately detect nodal involvement or small peritoneal metastasis is poor. The routine use of CT for imaging of the chest remains controversial for initial staging of colon cancer, as compared to rectal cancers. In asymptomatic patients in whom the suspicion of lung metastasis is low, a plain chest X-ray will suffice. Any suspicious findings on chest X-ray can be investigated with a noncontrast chest CT scan. As imaging technology has improved, so has the sensitivity of CT scans for identifying liver metastases. However, there are studies that suggest that contrast-enhanced magnetic resonance imaging (MRI) is particularly valuable in evaluating smaller suspicious liver lesions (especially in the presence of fatty liver changes) with sensitivities up to 97 % [3, 32]. In routine clinical practice, MRI should be reserved for the evaluation of suspicious liver lesions not clearly characterized on CT scan and for operative planning prior to liver metastasectomy. Positron emission tomography–computed tomography (PET/CT) scan has emerged as a useful imaging modality in

C.B. Aarons and N.N. Mahmoud

the evaluation of many cancers. However, for initial staging of colorectal cancer, the routine use of PET/CT remains ­controversial. While it has been shown to be more sensitive in the detection of liver metastases as well as extrahepatic disease as compared with routine CT scan, other studies suggest that it does not add significant information [14, 33–35]. The strongest evidence for use of PET/CT in the management of colorectal cancer is in the evaluation of patients with recurrent disease [34–36]. It is often more helpful as an adjunct to conventional imaging studies in patients suspected of having metastasis, especially those with a rising CEA level [31, 37]. Additionally, in patients with potentially resectable metastatic disease, PET/CT has been shown in a randomized trial to reduce the number of unnecessary laparotomies [38].

 reoperative Evaluation of Coexisting P Medical Conditions Regardless of the operative approach, colorectal procedures carry inherent risks, which can be divided into procedure-­ specific risks and cardiopulmonary risks. Therefore, a thorough history and physical examination encompassing the patient’s comorbidities is also vital. This is immensely important because surgical morbidity and mortality can be greatly improved by a careful assessment of organ-specific risks and, if feasible, preoperative optimization. Additionally, a detailed knowledge of the patient’s prior abdominal surgery will aid in the appropriate operative planning. Routine preoperative testing should be obtained and should include a CBC, a metabolic panel, type and screen, and a 12-lead electrocardiogram in older patients with cardiac risk factors. Liver function tests are not sensitive for liver metastasis and, therefore, are not required in the initial preoperative testing. Similarly, nutritional panels are not generally required unless there are significant concerns for underlying malnutrition. Complete optimization of nutritional parameters, either parenterally or enterally, typically takes weeks, which would delay surgery unnecessarily. There are several classification systems that have been reported, which aim to gauge the overall risk of the surgical patient. The American Society of Anesthesiologists (ASA) classification is the simplest and most commonly used system, which highlights the patient’s underlying illnesses that may impact outcomes from surgery [39, 40]: • • • •

ASA I—a normal healthy patient ASA II—a patient with mild systemic disease ASA III—a patient with severe systemic disease ASA IV—a patient with severe systemic disease that is a constant threat to life • ASA V—a moribund patient who is not expected to survive without the operation • ASA E—emergency

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25.  Colon Cancer: Preoperative Evaluation and Staging

The preoperative cardiac assessment should include a history of recent or remote myocardial infarction, angina, valvular disease, arrhythmias, or heart failure. Baseline functional status should also be quantified using metabolic equivalents (METs) [41]. Perioperative risk of an adverse cardiac event can then be estimated using the Goldman cardiac risk index or the revised cardiac risk index (Table 25-1), which are among the most widely used tools for cardiac risk assessment [39]. Chronic obstructive pulmonary disease (COPD), obesity, obstructive sleep apnea, pulmonary hypertension, recent respiratory infection, and smoking are some of the most important pulmonary risk factors that should be considered prior to surgery. These comorbidities can be gleaned from a thorough history and should prompt further investigation; however, this testing should be selective. The routine use of chest X-ray varies by institution and is often of limited value for the evaluation of significant pulmonary disease; therefore, this study should be reserved for patients with known cardiopulmonary disease or those older than 50 years of age as recommended by the American College of Physicians [42]. Because CXR is a part of staging of colon cancer, it is necessarily included in the preoperative evaluation. Pulmonary function testing and baseline arterial blood gases are not indicated routinely prior to abdominal surgery [43]. Complex patients with high-risk underlying pulmonary illnesses should be referred for pulmonary consultation prior to surgery for medical optimization and to outline appropriate perioperative strategies. Smoking cessation should be emphasized but should not delay surgery, as any substantial benefits would not be realized for several weeks. However, there may be ­measurable gains in improving postoperative wound healing [44]. A recent meta-analysis of randomized trials ­demonstrated that smoking cessation was associated with a 41 % relative risk reduction in postoperative pulmonary complications [44].

In patients with renal insufficiency, care must be taken with choosing preoperative bowel preparation, and special attention must be paid to perioperative fluid balances. Additionally, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers should be held the day prior to surgery to minimize the risk of profound hypotension during surgery.

Staging of Colon Cancer The preferred staging system for colon and rectal cancers is the TNM staging system put forth by the American Joint Committee on Cancer and the International Union Against Cancer (UICC) [4, 36]. This system, which is summarized in Table 25-2, consists of three categories: tumor depth of invasion, nodal involvement, and distant metastasis. Based on the clinical and pathologic data, the combination of these categories forms the final stage, which correlates with the overall prognosis. Recent analysis of survival outcomes in a large group of patients with invasive colon cancer from the Surveillance, Epidemiology, and End Results (SEER) population-­based database has led to the revision of the CRC TNM staging system in the 7th edition of the AJCC Cancer Staging Manual [45]. These changes include [6]: • Stage II is further subdivided into IIA (T3N0), IIB (T4aN0), and IIC (T4bN0). • Satellite tumor deposits in the pericolonic adipose tissue are classified as N1c. • Several stage III groups have been revised based on survival outcomes. • N1 and N2 subcategories are further subdivided according to the number of involved nodes to reflect prognosis. • T4 lesions are subdivided as T4a (tumor penetrates the surface of the visceral peritoneum) and as T4b (tumor directly invades adjacent organs or structures).

Table 25-1.  Revised cardiac risk index (RCRI) Risk factors 1. High-risk type of surgery (intraperitoneal, intrathoracic, or suprainguinal vascular procedures) 2. Ischemic heart disease 3. Congestive heart failure 4. History of cerebrovascular disease 5. Insulin therapy for diabetes 6. Preoperative serum creatinine > 2.0 mg/dL Risk classification (one point is assigned to each risk factor present) Class I (0 points) Class II (1 point) Class III (2 points) Class IV (≥3 points) a

Rates of major cardiac complicationsa (%) 0.50 1.30 3.60 9.10

Major cardiac complications include myocardial infarction, pulmonary edema, ventricular fibrillation or primary cardiac arrest, and complete heart block Adapted from Lee, TH et al., Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery Circulation 1999;100(10):1043–9 [63]

C.B. Aarons and N.N. Mahmoud

438 Table 25-2E.  TNM classification and AJCC 7th edition staging of colon cancer Primary tumor staging (T) T0 Tis T1 T2 T3 T4a T4b Regional lymph node staging (N) N0 N1a N1b N1c N2a N2b Distant metastasis staging (M) M0 M1a M1b Stage T 0 Tis I 1–2 IIA T3 IIB T4a IIC T4b IIIA T1–T2 T1 IIIB T3–T4a T2–T3 T1–2 IIIC T4a T3–T4a T4b IVA Any T IVB Any T

No evidence of primary tumor Carcinoma in situ Tumor invades submucosa Tumor invades the muscularis propria Tumor invades through the muscularis propria into the pericolonic tissue Tumor penetrates to the surface of the visceral peritoneum (serosa) Tumor invades and/or is adherent to other organs or structures No regional lymph node metastasis Metastasis in one regional lymph node Metastasis in 2–3 regional lymph nodes Tumor deposits in subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastases Metastasis in 4–6 regional lymph nodes Metastasis in seven or more regional lymph nodes No distant metastasis Metastasis confined to one organ or site Metastasis in more than one organ/site or the peritoneum N M N0 M0 N0 M0 N0 M0 N0 M0 N0 M0 N1–N1c M0 N2a M0 N1–N1c M0 N2a M0 N2b M0 N2a M0 N2b M0 N1–N2 M0 Any N M1a Any N M1b

With permission from Chang GJ et al., Practice parameters for the management of colon cancer. Dis Colon Rectum 2012;55(8):834. © Wolters Kluwer [4]

• M1 is subdivided into M1a (single metastatic site) and M1b (metastasis to more than one organ or the peritoneum). The completeness of resection should also be noted by the surgeon [4, 6, 46]: • R0—complete tumor resection with negative margins • R1—incomplete tumor resection with microscopic involvement of the margin • R2—incomplete tumor resection with gross residual disease that was not resected In addition to the aforementioned components of the TNM staging system, there are several other histologic criteria that should be reported routinely. These include histologic grade, tumor (“satellite”) deposits, lymphovascular invasion,

perineural invasion, and margin status (distal, proximal, and radial). Each of these features provides important prognostic information.

Histologic Grade Histologic grade has consistently been shown to be a stage-­ independent prognostic factor and is determined by the degree of differentiation in the colon tumor. While most systems stratify cancers into four grades, ranging from well differentiated (grade 1) to undifferentiated (grade 4) [46], histologic assessment is often plagued by interobserver variability. Consequently, the AJCC has recommended a two-­tiered system for reporting: low grade (well and moderately

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25.  Colon Cancer: Preoperative Evaluation and Staging

differentiated) and high grade (poorly differentiated and undifferentiated) [21, 46, 47]. There are histologic variants such as mucinous adenocarcinomas and signet ring cell adenocarcinomas that are also important in assessing overall prognosis. Mucinous adenocarcinomas are characterized by extracellular mucin in greater than 50 % of the tumor volume. When compared with conventional invasive adenocarcinomas, mucinous adenocarcinomas typically behave more aggressively, especially in patients without microsatellite instability (MSI). Signet ring cell adenocarcinomas are rare but when they occur in the colon, they carry a worse prognosis as compared with conventional adenocarcinomas [14]. These tumors are characterized histologically by greater than 50 % tumor cells with signet ring features—prominent intracytoplasmic mucin vacuole that pushes the nucleus to the periphery [47].

Lymph Node Evaluation Other than radial margin status, lymph node status is the most important prognostic factor following resection of colon cancer [14]. The identification of at least 12 lymph nodes has been suggested as a key quality indicator in the resection of colon cancers [6]. While there are patient-related factors that influence lymph node yield, the completeness of mesenteric resection and the interest of the pathologist in obtaining the maximal number for nodes for examination are also paramount. Numerous studies have shown that increasing the number of lymph nodes examined is associated with improved survival in stage II and stage III patients [48]. Tumor deposits that are found in the pericolonic fat that do not show any evidence of residual lymph node are not counted as lymph nodes replaced by tumor and are designated as N1c. The number of these nodules should be reported as they confer a poor prognosis [6, 49]. During the past 20 years, there has been interest in improving harvest of at-risk lymph nodes and in better identification of tumor in lymph nodes. Some investigators have proposed injection of vital dye around the tumor at the time of operation as a method of identifying lymph nodes at greatest risk for metastases (sentinel node mapping). Studies of sentinel lymph node mapping have focused on the detection of metastatic lesions in nodes that would ordinarily be missed by routine nodal retrieval and pathologic processing. However, with few exceptions, the “sentinel” nodes retrieved in these studies have been subjected to ultraprocessing (microsectioning, immunohistochemical analysis, or RT-PCR), while other “nonsentinel” nodes have been examined by bivalving and hematoxylin and eosin staining only, biasing the results heavily in favor of sentinel lymph node mapping. Even with this bias, results have varied widely in the literature, with false-negative rates (patients

with negative “sentinel” nodes and positive “nonsentinel” nodes/total patients with positive nodes) of 9–60 % [50–52]. Variation in reported success rates may also result from ­different methods of data analysis and presentation. The ultimate goal of any protocol examining lymph nodes in nonstandard fashion is to identify patients with occult nodal metastases, to treat them with chemotherapeutic agents, and to improve survival. At present, there is no definitive evidence that treatment of patients with occult nodal metastases with chemotherapy improves survival.

Margin Status Surgical resection with curative intent requires removal of the entire tumor as well as the associated lymphatics and nodal basin at risk, which will vary based on the location of the primary tumor. It would seem obvious that it is of critical importance to resect the entire tumor when operating for colon cancer. However, the concept that the radial margin of resection is important was largely ignored by the surgical and pathology communities until recently. Just as with rectal cancer, it is important to ink the radial margin of resection and assess it histologically, as it has profound prognostic ­significance and will drive some decisions regarding adjuvant treatment and can be used as an assessment of surgical quality. It should be noted that the visceral peritoneum is not considered a surgical margin. However, pathologists often have difficulty in assessing this layer in relation to margin status, making inking of the nonperitonealized radial margin all the more critical. The proximal and distal margin of resection should also be measured and reported. Traditionally, some authors have advocated obtaining a 5 cm segment of normal bowel on the proximal and distal sides of the tumor to avoid local failure [4, 46, 53]. However, this recommendation has little to do with the primary tumor, as colon cancers do not often spread longitudinally in the wall of the bowel in occult fashion. Rather, the recommendation arises from the need to resect mesentery surrounding the tumor to ensure adequate removal of at-risk lymph nodes. Adequate resection of the mesentery, including named feeding vessels, will result in devascularization of the colon surrounding the tumor, thus mandating resection of the colon rendered ischemic.

Other Prognostic Features The presence of lymphovascular and perineural invasion has been shown to be significantly associated with poorer prognosis [21, 46, 54–57]. Tumor budding refers to small clusters of undifferentiated cancer cells ahead of the invasive front of the lesion. While this is not a routinely examined pathologic parameter, there is increasing evidence that the quantitative

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assessment of tumor budding reflects clinical aggressiveness of colon cancers. This has also been shown by some to be a poor prognostic feature [46, 54].

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26 The Surgical Management of Colon Cancer Matthew G. Mutch

Key Concepts • Complete clinical staging for colon cancer includes a total colon exam; computed tomography of the chest, abdomen, and pelvis; and a serum CEA level. • The principles of an oncologic resection include a total mesocolic resection, a ligation of the primary vessel at its origin, a wide mesenteric resection with >12 lymph nodes examined, and at least a 5 cm resection margin. • There is no difference in cancer-related outcomes for open and laparoscopic resections. • Anastomotic assessment for left-sided anastomosis is associated with a decreased leak rate. • Surgical resection is the most effective therapy for patients who present with obstruction colon cancers. • Endoscopic stenting of an obstructing colon cancer is an effective bridge to surgery within 72 h. • Perforated cancers should be treated with an oncologic resection. • First-line therapy for patients with metastatic colon cancer and an asymptomatic primary tumor is chemotherapy.

Introduction Our understanding of the pathogenesis, staging, and management of adenocarcinoma of the colon has evolved greatly over the last decade. Today, it is accepted that colorectal cancers develop via one of three distinct genetic pathways: (1) chromosomal instability, (2) mismatch repair, and (3) CpG island hypermethylation. This increased understanding of the genetics of colorectal cancer development has led to the identification of several putative molecular markers to predict their biologic and clinic behavior. However, pathologic staging using the TNM system remains the most valuable prognostic tool available, with depth of invasion (T stage) and lymph node involvement (N stage) being the best markers to risk stratifying regional and distant metastatic spread,

respectively. Preoperative imaging has allowed for more accurate clinical staging and earlier detection of metastatic disease that may impact the treatment of the patient. Advances in chemotherapy have allowed for improved outcomes for patients with selected stage II and stage III and IV cancers. Despite all of these advances, surgical resection remains the cornerstone and most important facet in the management of colon cancer. An intimate understanding of the anatomy of the colon, its vasculature, and the retroperitoneum are critical to performing an appropriate oncologic resection for colon cancer. This chapter will focus on the technical aspects of the principles of an oncologic resection such as the importance of total mesocolic resection, ligation of primary vasculature at its origin, obtaining an adequate lymph node harvest to ensure an examination of >12 lymph nodes, and obtaining appropriate distal and proximal margins for open and laparoscopic resections. Special topics such as laparoscopic colectomy for cancer, management of obstructing and perforated colon cancers, treatment of the primary tumor in the setting of metastatic disease, and the short-term and long-term outcomes for colectomy for cancer will be addressed.

Preoperative Preparation When preparing to take a patient to the operating room for resection of his/her colon cancer, it is imperative to have a complete understanding of the patient’s physiologic status, tumor location, and clinical staging. Being able to provide patients with individualized risk stratification for complications after colorectal surgery is becoming more and more important because of the increasing scrutiny of patient safety and outcomes. The general population in the USA is getting older and has an increasing number of comorbidities, so ­surgeons will be making more and more challenging decisions regarding the management of patients with colorectal cancer.

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_26

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Physiologic Assessment

Tumor Localization

A variety of scoring systems are available for stratifying a patient’s risk of perioperative morbidity and mortality after undergoing major digestive system surgery. Each scoring system differs in the included parameters and the outcomes that they measure. The most widely utilized scoring system is the American Society of Anesthesia (ASA) score, but it only provides assessment of an anesthesia complication for a given patient’s physiologic status. In contrast, the Physical and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) and modified Portsmouth-POSSUM scoring systems provide an ­assessment of the risk of postoperative mortality and morbidity [1]. The scoring system includes 12 preoperative physiologic factors such as age, blood pressure, heart rate, electrocardiogram status, hemoglobin, and electrolytes. It can also be reevaluated in the postoperative period using six additional intraoperative parameters including operative procedure, estimated blood loss, peritoneal contamination, presence of malignancy, and urgency of the operative procedure. However, it has been repeatedly shown that POSSUM and P-POSSUM scores underestimate the risk of morbidity and mortality for patients undergoing major colorectal surgery. In an effort to improve the performance prediction of patients undergoing colorectal resections, a colorectal-specific POSSUM (CR-POSSUM) score was developed [2]. Multiple retrospective and ­prospective studies have demonstrated improved accuracy with the CR-POSSUM compared to POSSUM and P-POSSUM for predicting mortality after colorectal surgery for a variety of diseases such as cancer and diverticulitis [3, 4]. The CR-POSSUM scoring system has also been validated in multiple health-care systems around the globe such as the USA, the UK, India, Middle East, Caribbean, and Asia [5, 6]. Furthermore, the CR-POSSUM scoring system has improved accuracy in elderly patients defined as >80 years of age when compared to P-POSSUM [7]. There are also suggestions that physiologic health status of an elderly patient is more important than the type of surgery when attempting to predict mortality in this age group. The American College of Surgeons developed a surgical risk calculator using data from National Surgical Quality Improvement Program (NSQIP) to provide patient-specific postoperative risks of various complications. The scoring system is based on over 1.4 million patients with over 1500 unique Current Procedural Terminology (CPT) codes and has performed very well for predicting mortality, overall morbidity, and risk of six specific complications (pneumonia, cardiac, surgical site infection, urinary tract infection, venous thromboembolism, renal failure, and return to the operating room) [8–10]. The NSQIP risk calculator has been shown to underestimate the risk of complications for colorectal resections, and more surgeon- and patient-specific data are needed. However, it remains a useful tool to preoperatively assess morbidity and mortality risk. The risk calculator is available at http://riskcalculator.facs.org.

Accurate tumor localization is a critical component of the preoperative assessment of the patient and operative planning. Intraoperative tumor localization can be challenging from several standpoints such a small or early tumor, obese patient, adhesions, laparoscopy, or inadequate tattooing. The utilization of intraluminal anatomic markings for tumor localization is inaccurate, 12–14 % of the time, and may be higher if cecal and rectal tumors are excluded [11]. In other words, the colonoscopy will not accurately locate the tumor 1 out of 7 times. Localization with endoscopic tattooing provides the most accurate method for localization. The tattoo should be placed distal to the lesion and in three separate areas around the circumference of the lumen (Fig. 26.1). A single injection into the mesenteric border or sprayed into the peritoneal cavity may be difficult to identify. Chou et al. reported that endoscopic tattooing provided accurate localization in 94 of 97 (98 %) tumors [12]. This study also examined radiographic methods for tumor localization and found barium enema and CT colonography to be 93 % and 95 % accurate, respectively. Alternatively, endoscopic placement of metal clips at the site of the tumor with immediate plain radiograph (or CT) will localize the tumor with a high degree of accuracy. The ultimate fallback to identify a lesion is intraoperative colonoscopy, ideally using carbon dioxide as the insufflation gas to limit bowel dilatation. Patients who present with endoscopically obstructing lesions can be effectively evaluated with CT colonography to complete their total colon exam prior to surgery. CT ­colonography has replaced contrast enema studies in many situations because of improved accuracy in detecting synchronous lesions and often provides better tumor localization. A study of 411 consecutive patients evaluated with CT colonography for incomplete colonoscopy due to a stenosing colorectal cancer and the preoperative CT colonography was compared to the intraoperative and pathologic findings [13]. The study demonstrated a sensitivity of 100 % for detecting

Figure 26-1.  Tattoo localization of a sigmoid colon cancer.

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proximal synchronous cancers and negative predictive value of 97 % for identifying advanced neoplastic lesions (advanced adenomas or cancers). Other studies have demonstrated similar results [14–16]. CT colonography can safely be used in the acute and subacute settings as demonstrated by Maras-­Simunic et al. [17]. They examined 44 patients who presented with signs and symptoms of a large bowel obstruction, and CT colonography was able to accurately identify the cause of obstruction as a cancer in 41 and due to a benign process in nine patients. It was also able to accurately detect two synchronous cancers in this small study population. Therefore, if it is safe and feasible, patients presenting with a distally obstructing lesion (clinically or endoscopically) who have a negative CT colonography can be safely treated with a segmental resection without significant risk of missing of synchronous, proximal lesions.

Surgical Technique Extent of Resection The National Comprehensive Cancer Network provides the recommended principles of surgical resection for colon cancer, which include obtaining an adequate proximal margin, distal margin, and lymphadenectomy [18]. Colon cancers tend to grow circumferentially around the lumen of the colon, extend out radially and, to a lesser degree, longitudinally along the bowel. Therefore, a 5 cm proximal or distal margin has always been recommended. This is important to remove all tumors bearing mucosa but also to resect all lymph nodes with potential to drain tumor cells. A retrospective study by Rorvig et al. compared final pathologic stage in resected colon cancer specimens with a tumor margin 5 cm margin. The node positivity rate for tumors with a margin 5 cm [19]. This highlights that even though the primary tumor does not grow in a longitudinal fashion, lymphatic drainage can extend in a longitudinal or somewhat aberrant fashion. In order to obtain an adequate lymphadenectomy, the feeding vessel to the resected segment of the colon should be taken at its origin. For example, the ileocolic pedicle should be ligated at its origin on the superior mesenteric artery, and the inferior mesenteric artery should be ligated at the level of the aorta. The goal is to clear all regional lymph nodes and provide a minimum of 12 lymph nodes for pathologic evaluation. The impact of an adequate lymph node harvest and evaluation on the accuracy of pathologic staging is well documented and is addressed in Chap. 34. The concept of high versus low ligation of the primary feeding vessel had been debated throughout the literature. Historical data and recent prospective randomized trials have demonstrated no difference in morbidity associated with high ligation [20–23]. However, the rate of positive lymph nodes along the IMA above the level of aortic bifurcation has been reported to be as high as 8 % and when resected is associated with better disease-free survival [22]. Therefore, to maximize the lymph

node harvest and to ensure complete resection of potentially metastatic lymph nodes, the mesentery should be resected with the primary vessel ligated at its origin and at least a 5 cm margin distal or proximal to the tumor.

Mesocolic Resection The concept of total mesorectal excision (TME), which was popularized by R.J. Heald, also pertains to the resection of the colon and associated mesentery along the appropriate fascial planes. Just as the mesorectum is enveloped in a fascia, the mesocolon also has a visceral fascial plane that separates it from the retroperitoneum (parietal fascia). A serosal surface on the bowel and mesentery excludes the anterior aspect of the mesentery from the perineal cavity. Therefore, a complete mesocolic excision (CME) is the sharp dissection of the visceral fascia from the parietal fascia of the retroperitoneum and central ligation of the primary vasculature. Hohenberger et al. adopted this concept in the mid-1990s and published their results on 1329 consecutive patients [24]. They reported an improvement in 5-year local recurrence and 5-year survival from 6.5 to 3.6 % and 82.1 to 89.1 %, respectively, after adoption of CME plus central ligation of the mesenteric vessels. Subsequent studies have demonstrated several other benefits of CME such as increased lymph node harvest, longer vascular ligation, increased resection of extranodal tumor deposits, and increased upstaging, which led to no differences in morbidity but improved locoregional control and survival [25, 26]. The technical concept of sharp dissection of the colon and mesocolon off the retroperitoneum, excision of the mesentery along the lines of resection, and central ligation of the vasculature is as important to colon cancer as TME is to rectal cancer.

Right Colectomy Tumors located anywhere from the cecum to the proximal transverse colon can safely be treated with a right colectomy. The basic tenets of resection of a right-sided tumor include full abdominal exploration, full mobilization of the right colon, and hepatic flexure with a mesenteric resection including ligation of the ileocolic and right branch of the middle colic vessels at their origin. The resection can be performed safely and effectively via either an open or laparoscopic approach. Data regarding laparoscopy and colorectal cancer is presented in detail below.

Open Approach The peritoneal cavity can be accessed with a midline incision or as some surgeons prefer a right-sided transverse incision. Once the abdomen is open, explored, and the tumor is located, the wound should be protected with a wound protector. The first step in mobilizing the right colon is to access the retroperitoneum, which can be accomplished laterally along the

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white line of Toldt, inferiorly near the cecum, posteriorly under the small bowel mesentery, or superiorly through the lesser sac. Once the retroperitoneum is entered, the mesentery and hepatic flexure are mobilized. The duodenum should be identified and reflected into the retroperitoneum. The omentum associated with the resected colon should be resected as well. With the colon completely mobilized, the vascular pedicles can be ligated. Regardless of the approach used, the step is the same and only their order is different.

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Posterior Approach The small bowel is eviscerated and reflected toward the right upper quadrant to expose the posterior aspect of the small bowel mesentery from the ligament of Treitz to the cecum (Fig. 26.2). The peritoneum is incised along this entire length, and the retroperitoneum is entered (Fig. 26.3). The duodenum is readily identified and reflected into the retroperitoneum.

Lateral Approach The surgeon stands on the patient’s left side and the first assistant on the patient’s right side. The right colon is grasped, and the peritoneum is incised just anterior to the white line of Toldt from the cecum to the hepatic flexure. This allows access to the retroperitoneum or the avascular plane between the visceral and parietal planes of the colon and retroperitoneum. It is important not to violate the mesenteric side of this plane in order to ensure a total mesocolic resection. Under tension, the right colon is separated sharply from the retroperitoneum. The duodenum should be identified and reflected into the retroperitoneum. The cecum is then mobilized off the retroperitoneum, and the posterior attachments of the small bowel mesentery are divided all the way up to the duodenum. This provides the mobility of the small bowel for the anastomosis. With the duodenum safely reflected posteriorly, the hepatic flexure can be mobilized. The surgeon’s left hand is placed under the colon and its mesentery and brought out laterally to expose the superior attachments along the inferior edge of the liver. Eventually, the lesser sac is entered, and the lesser omentum is divided. Care must be taken so the plane between the omentum and the transverse colon mesentery is separated, and dissection into the transverse colon is avoided. These two planes are typically fused up to the midline, and beyond this point, the proper lesser sac is entered. After the right colon and hepatic flexure are completely mobilized, the cecum is put on stretch, and the ileocolic pedicle can easily be identified. Since the right colon and its mesentery have been mobilized, there should be bare areas on the cephalad and caudad aspects of the ileocolic pedicle. The peritoneum is incised along the lines of resection for both bare areas allowing isolation of the pedicle so it can be ligated at its origin on the superior mesenteric vessels. The terminal ileal mesentery is divided so that a 5 cm margin on the terminal ileum is obtained. The right branch of the middle colic vessels is identified by elevating the transverse colon mesentery. The pedicle should become evident either by it bowstringing under tension or there should be another bare area where the omentum has been dissected free during the exposure of the lesser sac. The peritoneum should be incised from the distal site of transection of the colon to the base of the pedicle and across the pedicle to the cut edge of the right colon mesentery. The pedicle can then be ligated at its origin. Ileocolic anastomotic techniques will be discussed later.

Figure 26-2.  Exposure of the posterior aspect of the small bowel mesentery for the posterior approach to a right colon.

Figure 26-3. Entry into the retroperitoneum from the posterior approach to a right colectomy.

26.  The Surgical Management of Colon Cancer

The right colon mesentery is elevated off the retroperitoneum out beyond the ascending colon laterally and the transverse colon superiorly. The further this dissection can be performed from a medial-to-lateral direction beyond the transverse colon, hepatic flexure, and ascending colon, the easier the lateral dissection becomes as all that remains are the lateral peritoneal and lesser omental attachments. At this point, starting at the level of the cecum, the surgeon while standing on the patient’s left side places his/her left hand under the right colon mesentery and lateral to the colon to expose the lateral peritoneal attachments. These are then divided heading up toward the hepatic flexure. If the dissection is continuing easily, the lesser omentum is separated from the transverse colon mesentery in order to enter the lesser sac. If this plane is difficult to develop, the distal site of transection is identified, and the lesser sac can be entered at this point. This begins by dividing the greater omentum to the level of the colon, and the lesser omentum is bluntly separated from the colon and its mesentery to enter the lesser sac. Once the lesser sac is entered, this plane is developed toward the hepatic flexure. Eventually, the posterior retroperitoneal dissection plane is entered. With the duodenum free, the remaining attachments along the inferior liver can be safely divided. The right colon and hepatic flexure are completely mobilized so the vascular pedicles can be ligated and the mesentery can be resected as described above.

Superior Approach This dissection begins at the distal site of transection of the transverse colon. This is accomplished by elevating the transverse colon to expose its inferior aspect of the mesentery so the right branch of the middle colon vessels can be identified. It is the first pedicle medial to the bare area of the duodenum and should bowstring under the tension of elevating the transverse colon. The greater omentum is divided up to the transverse colon, and the lesser omentum is separated from the colon and mesentery to enter the lesser sac. As this plane is developed toward the hepatic flexure, the lesser omentum is divided. The stomach superiorly and duodenum posteriorly should be identified and separated from the colon mesentery. Once the lesser omentum or hepatic attachments to the colon are divided beyond the hepatic flexure, the hepatic flexure can be elevated under tension to develop the retroperitoneal plane, identify and free the duodenum, and divide the lateral peritoneal attachments of the right colon. With the peritoneal attachments divided, the remaining colon is mobilized in the same manner as described in the lateral approach. The superior approach is very useful for big bulky or locally advanced tumors of the cecum and proximal ascending colon because it allows for complete mobilization of the colon and mesentery before addressing the site of the tumor.

Anastomosis The anastomosis can be accomplished via handsewn or stapled techniques. For the handsewn technique, the anastomotic orientation can either be end to end or side to side, and it can

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be created in a single or double layer of sutures. However, an end-to-end anastomosis is often difficult given the significant size discrepancies between the lumens of the small bowel and colon, so only the side-to-side technique will be presented. For the handsewn technique, the bowel is divided with a stapler or sharply, and the cut edges are closed with an absorbable monofilament 3-0 suture. To close the enterotomy, a Connell stitch is used in a running fashion, and this suture line can be dunked with interrupted Lembert stitches using an absorbable 3-0 suture. The bowel is then oriented in a side-toside, antiperistaltic fashion. A single-­layer anastomosis can be created using an absorbable monofilament 3-0 suture in either a running or interrupted fashion. For a single-layer, interrupted anastomosis, a 6–7 cm enterotomy is created. The first two stitches are placed 180° from each other in the proximal and distal corners, which allows for the “back walls” of the anastomosis to be aligned. With the “back wall” edges of the anastomosis inverted, the next stitch is placed in a bisecting position, and the subsequent stitches are placed in the same bisecting fashion until the “back wall” is complete. For the “front wall” of the anastomosis, sutures are alternately placed at proximal and distal corners until they meet in the middle. The suture is place from an inside out of the first lumen to the outside in of the second lumen. This technique places the knot of the suture intraluminally and inverts the two edges of the bowel. The last stitch will need to be placed in an out-to-in and in-to-out fashion, so the knot is on the outside of the bowel. For a running handsewn anastomosis, two sutures are placed in the middle of the “back wall” of the anastomosis, so one suture will run the anastomosis in the proximal direction and the other suture will run in the distal direction, and after completing the “front wall,” the two sutures will be tied together. For the “back wall” of the anastomosis, the suture can be run in an overlapping, baseball-type fashion as the two bowel edges are already inverted. At each corner as the “front wall” of the anastomosis is created, the stitch should be transitioned to a Connell stitch, so the front edges will be inverted as well. For a double-layered anastomosis, the first step is to place the back row of Lembert stitches along the length of the anastomosis. The enterotomies are then made parallel to the Lembert stitches, and the inner layer is created in the same fashion of the running anastomosis described above. The front outer layer of Lembert stitches are then placed once the inner layer is completed. Stapled anastomoses are most commonly performed in a side-to-side fashion but can also be performed in a side-to-­ end configuration as well. The traditional side-to-side, stapled anastomosis is created by individually dividing the proximal (Fig. 26.4) and distal limbs (Fig. 26.5) of the bowel with a stapler. The antimesenteric corner of each staple line is then excised, and forks of the stapler are placed into the lumen of each limb of the intestine. The stapler is reassembled and fired with the bowel in an antiperistaltic and antimesenteric fashion (Fig. 26.6). The resulting common enterotomy is reapproximated, so the longitudinal staple lines are offset, which prevents the intersection of more than two staple lines (Fig. 26.7). This common enterotomy can be

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Figure 26-4.  Division of the terminal ileum. Courtesy of Howard Ross, M.D.

Figure 26-5.  Division of the transverse colon. Courtesy of Howard Ross, M.D.

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Figure 26-6.  Firing of the linear stapler for a side-to-side stapled anastomosis. Courtesy of Howard Ross, M.D.

Figure 26-7. Closing the common enterotomy by offsetting the longitudinal staple line. Courtesy of Howard Ross, M.D.

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closed with suture or staples (Figs. 26.8 and 26.9). An alternative method for creating the side-to-side anastomosis is not to divide the proximal and distal bowel. Enterotomies are then made on the antimesenteric side at the site of transection. The forks of the staple are then passed through each enterotomy where they are reassembled and fired in an antiperistaltic and antimesenteric fashion. The common enterotomy is once again reapproximated with the longitudinal staple lines offset, and then it is closed with a firing of the stapler that incorporates the proximal and distal limbs of the bowel. This technique saves the use of two stapler loads. A stapled anastomosis can also be created in a side-to-end fashion. This anastomosis is created with an end-to-end anastomotic (EEA) stapler. The distal limb is divided sharply; a purse string is placed; and the stapler anvil, typically 28 or 29 mm, is placed inside. The proximal limb is also divided sharply, and the stapling cartridge is passed into the lumen of the proximal bowel. It is aligned for the spike to come out through the antimesenteric border. The spike should be positioned proximal enough, so the distal aspect of the circular staple line is at least 4 cm proximal to the cut edge of the bowel. This is important to ensure that the distal strip of the bowel remains viable once the enterotomy is closed. The end

enterotomy of the proximal limb is then closed with a linear stapler or can be handsewn.

Figure 26-8. Closing the common enterotomy for a side-to-side anastomosis. Courtesy of Howard Ross, M.D.

Figure 26-9.  Complete side-to-side ileocolic anastomosis. Courtesy of Howard Ross, M.D.

Laparoscopic Approach Proper room setup and instrumentation are critical for success. A mechanical bed is essential, so the patient can be placed in extremes of positions to maximize the use of gravity for retraction and exposure. The patient needs to be safely secured to the bed, and there are a myriad of techniques to accomplish this such as bean bags, nonskid pads, or shoulder braces. Placing the patient in stirrups has the advantage of allowing the assistant or surgeon to stand between the legs, which allows for visualization in the direction of the dissection and minimizes working against the camera angle. Instrumentation is up to the surgeon’s preference, but the use of atraumatic graspers is recommended. There are several energy devices available such as monopolar cautery, bipolar vessel sealers, and ultrasonic sealers that can be used for dissection and ligation of appropriate vessels. With regard to port placement, there are no hard-set rules, and they should be based on the surgical approach and surgeon’s preference (Fig. 26.10a, b). Laparoscopic colectomy is a multi-quadrant procedure, so placement of the camera port as to maximize visualization is important. The most optimal place for the

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Figure 26-10.  (a) Port placement for a laparoscopic right colectomy, (b) port placement for a laparoscopic right colectomy.

camera port is at the apex of the pneumoperitoneum. This is typically in the midline and at the midpoint between the xiphoid process and the pubic symphysis, which can either be above or below the umbilicus. Once pneumoperitoneum is established and the abdomen is adequately explored, the dissection can be carried out in a medial-to-lateral, lateral-to-­ medial, or posterior approach. For this chapter, the medial-­ to-­lateral and posterior approaches will be presented.

Medial-to-Lateral Approach Once the peritoneum is accessed, pneumoperitoneum is established and the ports are placed, the abdomen is completely examined, and the tumor is localized. The patient is then placed in steep Trendelenburg and airplaned right-side up. The omentum is placed in the upper abdomen to expose the transverse colon and the hepatic flexure. The small bowel is moved to the left side of the abdomen to fully expose the right colon mesentery. The first step of the dissection is to grab the mesentery at the junction of the terminal ileum and cecum and pull it to the right lower quadrant. This puts the ileocolic pedicle on tension and can be identified as it creates a bowstring in the mesentery. The pedicle is then grasped more proximally, and the peritoneum on the caudad aspect is incised in a direction parallel to the vessels. A wider incision in the peritoneum provides better exposure. Blunt dissection is used to get through the mesentery into the retroperitoneum. Once in the retroperitoneum, the duodenum is readily identified and reflected into the retroperitoneum. This dissection is aided by providing sufficient traction allowing tension, and 15 mmHg of CO2 pressure aids the development of the avascular planes between the visceral and parietal fascia of the retroperitoneum. The dissection is done bluntly and carried cephalad and lateral as far as possible to safely separate the duodenum from the right colon mesentery, which

allows the ileocolic pedicle to be isolated and ligated at its origin from the superior mesenteric vessels. The pedicle can be ligated with clips, staples, or vessel-sealing devices. In order to identify and isolate the right branch of the middle colic vessels, the transverse colon mesentery is elevated under tension. The pedicle is then identified as the vessel that bowstrings just medial to the cut edge of the right colon mesentery. This will help identify the distal site of transection of the colon. The peritoneum from the colon medial to the pedicle is scored down to the base of the pedicle and across it to the mesenteric cut edge. The pedicle is isolated with gentle blunt dissection along this plane. Once through the transverse colon mesentery, the omentum may be adherent to the mesentery in the lesser sac, so it may need to be dissected free to isolate the pedicle. With the pedicle ligated, the window through the mesentery into the retroperitoneum is wider, and the right colon mesentery should be mobilized off the retroperitoneum from the mid-transverse colon, out to the hepatic flexure, and lateral to the ascending colon. Ideally, all that remains at this point is the lateral peritoneal and omental attachments. The cecum is grasped and reflected medially and cephalad, the peritoneum is incised, and the dissected retroperitoneal space is entered. The posterior peritoneal attachments of the small bowel mesentery need to be divided up to the level of duodenum, so the small bowel has enough mobilization for extraction, resection, and anastomosis. Now the lateral attachments of the right colon are divided under tension all the way up the hepatic flexure. If the dissection is proceeding well, the hepatic flexure can be mobilized in this same direction by separating the hepatocolic/lesser omentum from the transverse colon mesentery to enter the lesser sac. If it is difficult to get adequate exposure, the approach can be altered by returning the colon to its anatomic position and identifying the distal site where the colon will be divided. The greater omentum is then divided at this point, and the

26.  The Surgical Management of Colon Cancer

lesser sac is entered by separating the lesser omentum from the transverse colon and its mesentery. This is an avascular plane, so it can be separated bluntly under tension. Once this plane has been developed, the dissection progresses toward the hepatic flexure by dividing the lesser omentum. As the dissection progresses beyond the pylorus, the retroperitoneal dissection plane should be entered, and the remaining attachments along the liver can be safely divided because the duodenum has been dissected free of this tissue. The colon is now completely mobilized and can be extracted via the surgeon’s site of choice. For cancer cases, the use of a wound protector for extraction is highly recommended to minimize the risk of a wound recurrence. Once the colon is extracted, it is resected, and the anastomosis can be created using one of the techniques described earlier.

Posterior Approach The peritoneal cavity is entered, ports are placed, and the abdomen is thoroughly explored. The patient is placed in steep Trendelenburg, and the omentum is reflected over the transverse colon to expose the hepatic flexure. The small bowel is placed in the right upper quadrant to expose the posterior aspect of the small bowel mesentery. The patient should not be tilted right-side up, so the small bowel will stay in the right upper quadrant. To obtain the exposure, the terminal ileum is identified and reflected toward the right colon. This will expose the fold of where the small bowel mesentery joins the retroperitoneum. Moving the small bowel to the right upper quadrant and following this fold in a cephalad direction will expose the fourth portion of the duodenum (Fig. 26.11). An instrument in the surgeon’s right hand elevates the proximal aspect of the small bowel mesentery under tension, and the first assistant via a right lower quadrant port elevates the distal aspect of the small bowel mesentery, which provides exposure of the duodenum and posterior peritoneum of the small bowel mesentery. With the use of an energy source, the

Figure 26-11. Exposure of posterior aspect of the small bowel mesentery for a laparoscopic posterior approach.

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peritoneum is incised from the duodenum to the cecum allowing access to the retroperitoneum, and the right colon mesentery can be elevated off the retroperitoneum. The duodenum is reflected posteriorly, and the mesentery is elevated from the mid-transverse colon, out to the hepatic flexure, and down the ascending colon to the cecum (Fig. 26.12). The further this dissection is carried beyond the colon laterally and superiorly, the easier the lateral and hepatic flexure mobilization will be. Now the patient is airplaned right-side up, and the small bowel and omentum are pulled to the left side of the abdomen to expose the lateral aspect of the right colon. The lateral attachments are divided by grabbing the cecum and retracting it medial and cephalad toward the spleen (Fig. 26.13). The attachments are divided toward the hepatic flexure as far as possible. Just like that described in the medial-to-lateral approach, if the lesser sac can be easily developed and entered, the dissection can proceed in this direction. If this approach is too difficult, place the colon back in its anatomic position, and identify the distal site where the colon will be

Figure 26-12.  Posterior mobilization of the right colon mesentery off the retroperitoneum.

Figure 26-13.  Exposure of the lateral attachments after the posterior dissection.

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divided. This is accomplished by elevating the transverse colon mesentery and putting the right branch of the middle colic vessels on stretch (Fig. 26.14). The vessel is medial to the bare area of the right colon mesentery. The greater omentum is then divided at this point, and the lesser sac is entered by separating the lesser omentum from the transverse colon and its mesentery (Fig. 26.15). This is an avascular plane, so it can be separated bluntly under tension. Once this plane has been developed, the dissection progresses toward the hepatic flexure by dividing the lesser omentum. As the dissection progresses beyond the pylorus, the retroperitoneal dissection plane can be identified by the purplish tissue planes indicative of the previous posterior dissection. This plane can be safely entered, and the remaining attachments along the liver can be safely divided because the duodenum has been dissected free of the right colon mesentery (Fig. 26.16). At this point, the right colon and hepatic flexure have been completely mobilized. The next step is to isolate and ligate the vasculature. The ileocolic pedicles are identified by grasping the mesentery on the inside of the ileocecal valve and pulling to the right lower quadrant. The pedicle will bowstring, and because

Figure 26-14. Exposure of the right branch of the middle colic vessels.

Figure 26-15. Entering the lesser sac by separating the lesser omentum from the transverse colon at the distal site of transection.

M.G. Mutch

it has been mobilized off the retroperitoneum, bare areas can be seen on the caudad and cephalad (bare area over the duodenum) aspects (Fig. 26.17). The peritoneum on the caudad aspect is scored parallel to the pedicle, and blunt dissection through the mesentery will allow entry into the retroperitoneum. The duodenum can be visualized to ensure it is completely free of the pedicle. The peritoneum is then scored over the base of the pedicle toward the cephalad bare area, and the pedicle is safely isolated and ligated. The medial cut edge of the mesentery near the right branch of the middle colic vessels is grasped and reflected to the video right, allowing any remaining attachments to the duodenum, stomach, or omentum which can be seen and gently sweep free. The transverse colon mesentery is then elevated under tension, which allows for the right branch to bowstring, and, ideally, a bare area is seen medial to the vessel (Fig. 26.18). The peritoneum is then scored from the colon down to the base of the vessel and then across it to connect with the cut edge of the mesentery. Blunt dissection of the bare area will allow access into the lesser sac and for safe ligation of the pedicle. Because the omentum has been previously dissected free from entering the lesser sac, the vessel can be safely ligated without the risk of injury to

Figure 26-16. Exposure of posterior dissection plane from the superior approach.

Figure 26-17.  Identification of the ileocolic pedicle.

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Figure 26-18.  Identification of the right branch of the middle colic vessels.

Figure 26-20.  Medial exposure of the IMA.

Figure 26-19.  Extraction of the right colon.

surrounding structures. The colon can now be extracted and resected and the anastomosis created as described in the medial-to-lateral section (Fig. 26.19).

Left Colectomy Open The patient is placed in the lithotomy position to have access to the perineum for the anastomosis and anastomotic assessment. One of the patient’s arms can be tucked to his/her side, and the Mayo stand for the scrub nurse can be placed over the patient’s head, or the scrub nurse can stand off one of the patient’s hips. The peritoneum is entered via a midline inci-

Figure 26-21.  Medial exposure of the IMV.

sion that allows for complete exploration and mobilization of the splenic flexure. With the abdomen open, a wound protector can be inserted, and a self-retaining retractor can be utilized. Initial exposure of the left colon anatomy is accomplished by packing the small bowel in the right upper quadrant, so the base of the left colon mesentery includes exposing the inferior mesenteric artery (IMA) at its origin (Fig.  26.20) and the inferior mesenteric vein (IMV) as it courses near the ligament of Treitz and inferior border of the pancreas (Fig. 26.21). The cecum and terminal ileum are also

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packed away to provide complete exposure into the pelvis and the sacral promontory. The dissection begins with division of the lateral attachments of the sigmoid colon to allow for visualization of the white line of Toldt from the upper rectum to the proximal descending colon. The sigmoid colon and descending colon are elevated and retracted medially, and a long incision is made in the peritoneum to enter the retroperitoneal plane. With adequate tension on the colon and its mesentery, the areolar plane of dissection along the retroperitoneal plane is easily identified. The dissection is facilitated by exposing and dividing the retroperitoneal attachments along a plane of dissection as long as possible. The sigmoid colon and its mesentery should be completely medialized to the midline to expose and identify the left ureter. The dissection is then carried toward the splenic flexure. Mobilization of the splenic flexure can be facilitated by dissecting the posterior aspect of the mesentery up to the inferior border of the pancreas. The anatomy of the splenic flexure can be obscured by attachments of the omentum to the descending colon or medial aspect of the transverse colon. Separating these attachments restores normal anatomy, which can make the splenic flexure mobilization much easier. The next goal is to enter the lesser sac, and this is accomplished by separating the omentum from the transverse colon. By incising the peritoneal layer along the length of the transverse colon, the lesser sac is eventually entered, and the posterior attachments of the omentum to the colon mesentery can be exposed and divided. This will allow the lesser sac to be completely exposed from the flexure to beyond midline. This will also expose the remaining lateral attachments of the flexure which can be divided by either retracting the colon medially or placing a hand into the retroperitoneum and rolling the colon medially over the hand. With the lesser sac completely open and the flexure mobilized, the posterior attachments along the inferior border of the pancreas can be divided. With the posterior mesenteric dissection carried all the way up to the inferior border of the pancreas, the surgeon’s right hand is passed into the ­retroperitoneum in the lateral-to-medial direction. The fold of the splenic flexure mesentery can be palpated and separated from the inferior aspect of the pancreas, and the overlying peritoneum is divided to the midline. Care should be taken not to injure the IMV as the dissection is carried medially. With the left colon and splenic flexure completely mobilized, the vascular pedicles can be isolated and ligated. The sigmoid colon is elevated and retracted laterally to expose the base of the mesentery at the level of the sacral promontory. The peritoneum is incised from just below the promontory toward the attachments of the proximal jejunum and ligament of Treitz. This will allow for the superior rectal artery to be elevated off the retroperitoneum and expose the lateral plane of dissection. The surgeon can then pass his/her right hand under the superior rectal artery and divide the cephalad attachments, so the IMA can be isolated at its origin from the aorta (Fig. 26.22). The artery is isolated by creating a window on its cephalad side and medial to the IMV. It can then be ligated once the left ureter is clearly out of harm’s

M.G. Mutch

Figure 26-22.  Isolation of the IMA.

Figure 26-23.  Isolation of the IMV.

way. The IMV is now elevated off the retroperitoneum and isolated at the inferior border of the pancreas, and its ligation will ensure adequate mobilization for a tension-free anastomosis (Fig. 26.23). This allows for complete exposure of the retroperitoneum (Fig. 26.24). The proximal site of transection is dependent upon the location of the tumor and should ensure a minimum of a 5 cm margin. The distal site of transection should be at the proximal rectum to ensure an adequate distal margin and avoid having distal sigmoid colon

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26.  The Surgical Management of Colon Cancer

Figure 26-24.  Left retroperitoneum.

included in the anastomosis. The rectum is stapled and divided with a linear stapler. The anastomosis is most easily accomplished with an end-to-end double-stapled technique (see Chap. 9). The anvil is placed in the proximal colotomy after the creation of a purse string. The purse string is tightened while ensuring that the edges of the colotomy are everted, so all edges of the colotomy are incorporated into the purse string. The stapling cartridge is passed transanally to the top of the rectal stump. The stapler head should be flushed with the transverse staple line. A rectal fold or pelvic adhesion will sometimes prevent the stapler head from sitting flush. If a rectal fold is preventing this, the rectum can be further mobilized and divided a few centimeters lower, and if it is a pelvic adhesion preventing passing of the stapling cartridge, further mobilization of the rectum will often be adequate to get the stapler up to the staple line. The spike of the stapler is deployed just anterior or posterior to the transverse staple line. The anvil is reassembled to make sure there is no twist in the left colon and its mesentery.

Anastomotic Assessment Anastomotic assessment with either an air leak test alone or combined with endoscopic visualization is critical to ensuring a safe anastomosis. Anastomotic assessment has been shown to be associated with a decreased incidence of anastomotic leak from left-sided anastomosis. Kwon et al. audited the data from the Washington state’s Surgical Care and Outcomes Assessment Program regarding the utilization and outcomes associated with routine testing of colorectal anastomosis [27]. For this study, anastomotic testing consisted of insufflation of Betadine, methylene blue, or air under pres-

sure, and an adverse event included a return to the operating room for an ostomy creation, anastomotic revision, or drainage of abscess associated with a documented leak. For hospitals where the surgeons routinely performed anastomotic leak tests (defined as occurring in >90 % of cases), there was a 75 % lower risk of anastomotic leak (adjusted OR, 0.50; 95 % CI, 0.05–0.99) compared to those hospitals that employed selective leak testing (adjusted OR, 2.68; 95 % CI, 1.14–6.26). A retrospective review by Ricciardi et al. demonstrated an overall leak rate of 4.8 % for 998 patients that underwent a left-sided colorectal anastomosis without proximal diversion [28]. Ninety percent of patients underwent air leak testing, and the associated leak rates were 7.7 % with a positive air leak test, 3.8 % with a negative air leak test, and 8.1 % when no air leak test was performed (p 65 years, by Age Group-­ National Hospital Discharge Survey United States, 1996-2009. MMWR Morb Mortal Wkly Rep. 2011;60(3): 1171–85. 9. Gupta SB, Dubberke ER. Overview and changing epidemiology of Clostridium difficile infection. Semin Colon Rectal Surg. 2014;25:118–23. 10. Kuijper EJ, Coignard B, Brazier JS, Suetens C, Drudy D, Wiuff C, Pituch H, Reichert P, Schneider F, Widmer AF, Olsen KE, Allerberger F, Notermans DW, Barbut F, Delmée M, Wilcox M, Pearson A, Patel BC, Brown DJ, Frei R, Akerlund T, Poxton IR, Tüll P. Update of Clostridium difficile-associated disease due to PCR ribotype 027 in Europe. Euro Surveill. 2007;12:E1–2. 11. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478–98. 12. US Institute of Peace. Roadmap to eliminate HAI: 2013 Action Plan Conference, Washington, DC, 25–26 Sept 2013. 13. Gould CV, Edwards JR, Cohen J, Bamberg WM, Clark LA, Farley MM, Johnston H, Nadle J, Winston L, Gerding DN, McDonald LC, Lessa FC, Clostridium difficile Infection Surveillance Investigators, Centers for Disease Control and

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D.B. Stewart rooms and its impact on endemic Clostridium difficile infection rates. Am J Infect Control. 2013;41(6):537–41. 68. Rupnik M, Dupuy B, Fairweather NF, Gerding DN, Johnson S, Just I, Lyerly DM, Popoff MR, Rood JI, Sonenshein AL, Thelestam M, Wren BW, Wilkins TD, von Eichel-Streiber C. Revised nomenclature of Clostridium difficile toxins and associated genes. J Med Microbiol. 2005;54:113–7. 69. Mani N, Dupuy B. Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor. Proc Natl Acad Sci U S A. 2001;98:5844–9. 70. Mani N, Lyras D, Barroso L, Howarth P, Wilkins T, Rood JI, Sonenshein AL, Dupuy B. Environmental response and autoregulation of Clostridium difficile TcdR, a sigma factor for toxin gene expression. J Bacteriol. 2002;184(21):5971–8. 71. Dupuy B, Govind R, Antunes A, Matamouros S. Clostridium difficile toxin synthesis is negatively regulated by TcdC. J Med Microbiol. 2008;57(Part 6):685–9. 72. Govind R, Vediyappan G, Rolfe RD, Fralick JA. Evidence that Clostridium difficile TcdC is a membrane-associated protein. J Bacteriol. 2006;188(10):3716–20. 73. Helmann JD. Anti-sigma factors. Curr Opin Microbiol. 1999;2(2):135–41. 74. Stewart DB, Berg A, Hegarty J. Predicting recurrence of C. difficile colitis using bacterial virulence factors: binary toxin is the key. J Gastrointest Surg. 2013;17(1):118–24. Discussion 124–5. 75. Stewart DB, Berg AS, Hegarty JP. Single nucleotide polymorphisms of the tcdC gene and presence of the binary toxin gene predict recurrent episodes of Clostridium difficile infection. Ann Surg. 2014;260(2):299–304. 76. Goldenberg SD, French GL. Lack of association of tcdC type and binary toxin status with disease severity and outcome in toxigenic Clostridium difficile. J Infect. 2011;62(5):355–62. 77. Cartman ST, Kelly ML, Heeg D, Heap JT, Minton NP. Precise manipulation of the Clostridium difficile chromosome reveals a lack of association between the tcdC genotype and toxin production. Appl Environ Microbiol. 2012;78(13):4683–90. 78. Davies AH, Roberts AK, Shone CS, Acharya KR. Super toxins from a super bug: structure and function of Clostridium difficile toxins. Biochem J. 2011;436(3):517–26. 79. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP. The role of toxin A and toxin B in Clostridium difficile infection. Nature. 2010;467(7316):711–3. 80. Jank T, Aktories K. Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol. 2008;16(5):222–9. 81. Jank T, Giesemann T, Aktories K. Rho-glucosylating Clostridium difficile Toxins A and B: new insights into structure and function. Glycobiology. 2007;17(4):15R–22. 82. Just I, Wilm M, Selzer J, Rex G, von Eichel-Streiber C, Mann M, Aktories K. The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J Biol Chem. 1995;270(23):13932–6. 83. Holbourn KP, Shone CC, Acharya KR. A family of killer toxins. Exploring the mechanism of ADP-ribosylating toxins. FEBS J. 2006;273(20):4579–93. 84. Geric B, Johnson S, Gerding DN, Grabnar M, Johnson S. Frequency of binary toxin genes among Clostridium difficile strains that do not produce large clostridial toxins. J Clin Microbiol. 2003;41(Pt 9):5227–32.

53.  Clostridium difficile Infection 85. Barth H. Uptake of binary actin ADP-ribosylating toxins. Rev Physiol Biochem Pharmacol. 2004;152:165–82. 86. Schwan C, Stecher B, Tzivelekidis T, van Ham M, Rohde M, Hardt WD, Wehland J, Aktories K. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. PLoS Pathog. 2009;5(10): e1000626. 87. Rupnik M, Avesani V, Janc M, von Eichel-Streiber C, Delmée M. A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol. 1998;36(8):2240–7. 88. Van de Berg RJ, Claas EC, Oyib DH, Klaassen CH, Dijkshoorn L, Brazier JS, Kuijper EJ. Characterization of a toxin A-negative, toxin B-positive Clostridium difficile isolates from outbreaks in different countries by amplified fragment length polymorphism and PCR ribotyping. J Clin Microbiol. 2004;42(3):1035–41. 89. von Eichel-Streiber C, Sauerborn M. Clostridium difficile toxin A carries a C-terminal repetitive structure homologous to the carbohydrate binding region of streptococcal glycosyltransferases. Gene. 1990;96(1):107–13. 90. Gurtler V, Wilson VA, Mayall BC. Classification of medically important clostridia using restriction endonuclease site differences of PCR-amplified 16S rDNA. J Gen Microbiol. 1991;137(11):2673–9. 91. See I, Mu Y, Cohen J, Beldavs ZG, Winston LG, Dumyati G, Holzbauer S, Dunn J, Farley MM, Lyons C, Johnston H, Phipps E, Perlmutter R, Anderson L, Gerding DN, Lessa FC. NAP1 strain type predicts outcomes from Clostridium difficile infection. Clin Infect Dis. 2014;58(10):1394–400. 92. Cartwright CP, Stock F, Beekmann SE, Williams EC, Gill VJ. PCR amplification of rRNA intergenic spacer regions as a method for epidemiologic typing of Clostridium difficile. J Clin Microbiol. 1995;33(1):184–7. 93. Bidet P, Barbut F, Lalande V, Burghoffer B, Petit JC. Development of a new PCR-ribotyping method for Clostridium difficile based on ribosomal RNA gene sequencing. FEMS Microbiol Lett. 1999;175(2):261–6. 94. Griffiths D, Fawley W, Kachrimanidou M, Bowden R, Crook DW, Fung R, Golubchik T, Harding RM, Jeffery KJ, Jolley KA, Kirton R, Peto TE, Rees G, Stoesser N, Vaughan A, Walker AS, Young BC, Wilcox M, Dingle KE. Multilocus sequence typing of Clostridium difficile. J Clin Microbiol. 2010;48(3):770–8. 95. Marsh JW, O’Leary MM, Shutt KA, Sambol SP, Johnson S, Gerding DN, Harrison LH. Multilocus variable-number tandem-­repeat analysis and multilocus sequence typing reveal genetic relationships among Clostridium difficile isolates genotyped by restriction endonuclease analysis. J Clin Microbiol. 2010;48(2):412–8. 96. Eyre DW, Fawley WN, Best EL, Griffiths D, Stoesser NE, Crook DW, Peto TE, Walker AS, Wilcox MH. Comparison of multilocus variable-number tandem-repeat analysis and whole-genome sequencing for investigation of Clostridium difficile transmission. J Clin Microbiol. 2013;51(12):4141–9. 97. Goorhuis A, Bakker D, Corver J, Debast SB, Harmanus C, Notermans DW, Bergwerff AA, Dekker FW, Kuijper EJ. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis. 2008;47(9):1162–70.

947 98. Walk ST, Micic D, Jain R, Lo ES, Trivedi I, Liu EW, Almassalha LM, Ewing SA, Ring C, Galecki AT, Rogers MA, Washer L, Newton DW, Malani PN, Young VB, Aronoff DM. Clostridium difficile ribotype does not predict severe infection. Clin Infect Dis. 2012;55(12):1661–8. 99. Archbald-Pannone LR, Boone JH, Carman RJ, Lyerly DM, Guerrant RL. Clostridium difficile ribotype 027 is most prevalent among inpatients admitted from long-term care facilities. J Hosp Infect. 2014;88(4):218–21. 100. Labbé AC, Poirier L, Maccannell D, Louie T, Savoie M, Béliveau C, Laverdière M, Pépin J. Clostridium difficile infections in a Canadian tertiary care hospital before and during a regional epidemic associated with the BI/NAP1/027 strain. Antimicrob Agents Chemother. 2008;52(9):3180–7. 101. Pettit LJ, Browne HP, Yu L, Smits WK, Fagan RP, Barquist L, Martin MJ, Goulding D, Duncan SH, Flint HJ, Dougan G, Choudhary JS, Lawley TD. Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism. BMC Genomics. 2014;15:160. 102. Merrigan M, Venugopal A, Malozzi M, Roxas B, Viswanathan VK, Johnson S, Gerding DN, Vedantam G. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J Bacteriol. 2010;192(19):4904–11. 103. Smits WK. Hype or hypervirulence. A reflection on problematic C. difficile strains. Virulence. 2013;4(7):592–6. 104. Heeg D, Burns DA, Cartman ST, Minton NP. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLoS One. 2012;7:e32381. 105. Akerlund T, Svenungsson B, Lagergren A, Burman LG. Correlation of disease severity with fecal toxin levels in patients with Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and toxin yields in vitro of corresponding isolates. J Clin Microbiol. 2006;44(2):353–8. 106. Kim J, Seo MR, Kang JO, Choi TY, Pai H. Clinical and microbiologic characteristics of Clostridium difficile infection caused by binary toxin producing strain in Korea. Infect Chemother. 2013;45(2):175–83. 107. Blossom DB, McDonald LC. The challenges posed by re-­ emerging Clostridium difficile infection. Clin Infect Dis. 2007;45(2):222–7. 108. Nale JY, Shan J, Hickenbotham PT, Fawley WN, Wilcox MH, Clokie MRJ. Diverse temperate bacteriophage carriage in Clostridium difficile 027 strains. PLoS One. 2012;7(5):e37263. 109. Sekulovic O, Meessen-Pinard M, Fortier LC. Prophage stimulated toxin production in Clostridium difficile NAP1/027 lysogens. J Bacteriol. 2011;193(11):2726–34. 110. Stabler RA, He M, Dawson L, Martin M, Valiente E, Corton C, Lawley TD, Sebaihia M, Quail MA, Rose G, Gerding DN, Gibert M, Popoff MR, Parkhill J, Dougan G, Wren BW. Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol. 2009;10(9):R102. 111. Janezic S, Zidaric V, Pardon B, Indra A, Kokotovic B, Blanco JL, Seyboldt C, Diaz CR, Poxton IR, Perreten V, Drigo I, Jiraskova A, Ocepek M, Weese JS, Songer JG, Wilcox MH, Rupnik M. International Clostridium difficile animal strain collection and large diversity of animal associated strains. BMC Microbiol. 2014;14:173.

948 112. Sangster W, Hegarty JP, Stewart Sr DB. Phage tail-like particles kill Clostridium difficile and represent an alternative to conventional antibiotics. Surgery. 2015;157(1):96–103. 113. Heinrichs JH, Therien AG. Prevention of Clostridium difficile infections—the role of vaccines and therapeutic immunoglobulins. Semin Colon Rectal Surg. 2014;25:153–7. 114. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342(6):390–7. 115. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhea. Lancet. 2001;357(9251): 189–93. 116. Leav BA, Blair B, Leney M, Knauber M, Reilly C, Lowy I, Gerding DN, Kelly CP, Katchar K, Baxter R, Ambrosino D, Molrine D. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010;28(4):965–9. 117. Chang TW, Lin PS, Gorbach SL, Bartlett JG. Ultrastructural changes of cultured human amnion cells by Clostridium difficile toxin. Infect Immun. 1979;22(3):795–8. 118. Gilligan PH. Contemporary approaches for the laboratory diagnosis of Clostridium difficile infections. Semin Colon Rectal Surg. 2014;25:137–42. 119. Lyrerly DM, Barroso LA, Wilkins TD. Identification of the latex test-reactive protein of Clostridium difficile as glutamate dehydrogenase. J Clin Microbiol. 1991;29(11):2639–42. 120. Turgeon DK, Novicki TJ, Quick J, Carlson L, Miller P, Ulness B, Cent A, Ashley R, Larson A, Coyle M, Limaye AP, Cookson BT, Fritsche TR. Six rapid tests for direct detection of Clostridium difficile and its toxins in fecal samples compared with the fibroblast cytotoxicity assay. J Clin Microbiol. 2003;41(2):667–70. 121. Debast SB, van Kregten E, Oskam KM, van den Berg T, Van den Berg RJ, Kuijper EJ. Effect on diagnostic yield of repeated stool testing during outbreaks of Clostridium difficile-associated disease. Clin Microbiol Infect. 2008;14(6):622–4. 122. Katzman M. Antibiotic therapy for Clostridium difficile infection. Semin Colon Rectal Surg. 2014;25:143–9. 123. Stewart DB, Yacoub E, Zhu J. Chemotherapy patients with C. difficile colitis have outcomes similar to immunocompetent C. difficile patients. J Gastrointest Surg. 2012;16(8):1566–72. 124. Jafari NV, Kuehne SA, Bryant CE, Elawad M, Wren BW, Minton NP, Allan E, Bajaj-Elliott M. Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). PLoS One. 2013;8(7):e69846. 125. Venugopal AA, Johnson S. Current state of Clostridium difficile treatment options. Clin Infect Dis. 2012;55(S2):S71–6. 126. Bassetti M, Villa G, Percori D, Arzese A, Wilcox M. Epidemiology, diagnosis and treatment of Clostridium difficile infection. Expert Rev Anti Infect Ther. 2012;10(12): 1405–23. 127. No authors. Recommendations for preventing the spread of vancomycin resistance. Recommendations of the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 1995;44(RR-12):1–13. 128. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee Jr JT. Prospective randomized trial of metronidazole versus vancomycin for Clostridium difficileassociated diarrhea and colitis. Lancet. 1983;2(8358):1043–6.

D.B. Stewart 129. Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996;22(5): 813–8. 130. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302–7. 131. Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR, Gerding DN. Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial. Ann Intern Med. 1992;117:297–302. 132. Kim PK, Huh HC, Cohen HW, Feinberg EJ, Ahmad S, Coyle C, Teperman S, Boothe H. Intracolonic vancomycin for severe Clostridium difficile colitis. Surg Infect (Larchmt). 2013;14(6):532–9. 133. Keller JJ, Kuijper EJ. Treatment of recurrent and severe Clostridium Difficile infection. Annu Rev Med. 2015;66:373–86. 134. Hashash JG, Binion DG. Managing Clostridium difficile in inflammatory bowel disease (IBD). Curr Gastroenterol Rep. 2014;16(7):393. 135. Sullivan KM, Spooner LM. Fidaxomicin: a macrocyclic antibiotic for the management of Clostridium difficile infection. Ann Pharmacother. 2010;44:352–9. 136. Whitman CB, Czosnowski QA. Fidaxomicin for the treatment of Clostridium difficile infections. Ann Pharmacother. 2012;46:219–28. 137. Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK, OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422–31. 138. Babakhani F, Gomez A, Robert N, Sears P. Postantibiotic effect of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile. Antimicrob Agents Chemother. 2011;55(9):4427–9. 139. Mullane KM, Miller MA, Weiss K, Lentnek A, Golan Y, Sears PS, Shue YK, Louie TJ, Gorbach SL. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis. 2011;53(5):440–7. 140. Babakhani F, Bouillaut L, Sears P, Sims C, Gomez A, Sonenshein AL. Fidaxomicin inhibits toxin production in Clostridium difficile. J Antimicrob Chemother. 2013;68(3): 515–22. 141. Cornely OA, Nathwani D, Ivanescu C, Odufowora-Sita O, Retsa P, Odeyemi IA. Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison. J Antimicrob Chemother. 2014;69(11):2892–900. 142. Nathwani D, Cornely OA, Van Engen AK, Odufowora-Sita O, Retsa P, Odeyemi IA. Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection. J Antimicrob Chemother. 2014;69(11):2901–12. 143. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg. 2011;254(3):423–7. Discussion 427–9.

53.  Clostridium difficile Infection 144. Dallal RM, Harbrecht BG, Boujoukas AJ, Sirio CA, Farkas LM, Lee KK, Simmons RL. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363–72. 145. Sailhammer EA, Carson K, Chang Y, Zacharias N, Spaniolas K, Tabbara M, Alam HB, DeMoya MA, Velmahos GC. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg. 2009;144(5):433–9. 146. Byrn JC, Maun DC, Ginglod DS, Baril DT, Ozao JJ, Divino CM. Predictors of mortality after colectomy for fulminant Clostridium difficile colitis. Arch Surg. 2008;43(2):150–4. Discussion 155. 147. Hall JF, Berger D. Outcome of colectomy for Clostridium difficile colitis: a plea for early surgical management. Am J Surg. 2008;196:384–8. 148. Bhangu A, Nepogodiev D, Gupta A, Torrance A, Singh P, West Midlands Research Collaborative. Systematic review and meta-­analysis of outcomes following emergency surgery for Clostridium difficile colitis. Br J Surg. 2012;99(11): 1501–13. 149. Stewart DB, Hollenbeak CS, Wilson MZ. Is colectomy for fulminant Clostridium difficile colitis life saving? A systematic review. Colorectal Dis. 2013;15(7):798–804.

949 150. Borody TJ, Finlayson S. Fecal microbiota transplantation for Clostridium difficile infection: a surgeon’s perspective. Semin Colon Rectal Surg. 2014;25(3):163–6. 151. Song Y, Garg S, Girotra M, Maddox C, von Rosenvinge EC, Dutta A, Dutta S, Fricke WF. Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection. PLoS One. 2013;8(11):e81330. 152. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 2010;44(5):354–60. 153. Yu S, Abdelkarim A, Nawras A, Hinch BT, Mbaso C, Valavoor S, Safi F, Hammersley J, Tang J, Assaly R. Fecal transplant for treatment of toxic megacolon associated with Clostridium difficile colitis in a patient with duchenne muscular dystrophy. Am J Ther. 2014 [Epub ahead of print] 154. Neemann K, Eichele DD, Smith PW, Bociek R, Akhtari M, Freifeld A. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient. Transpl Infect Dis. 2012;14(6):E161–5. 155. Lee M, Shelton AA, Concepcion WL, Bonham CA, Daugherty TJ. Fulminant Clostridium difficile colitis in a post-liver transplant patient. Dig Dis Sci. 2010;55(9):2459–62.

54 Radiation, Microscopic, Ischemic Colitis Isabelle Raîche and Husein Moloo

Key Concepts • Microscopic colitis is likely an underappreciated diagnosis. Although there is no “cure,” the quality of life for a patient can be improved significantly with treatment which is typically medical and rarely surgical. • Budesonide is the only evidence-based treatment for microscopic colitis • Radiation colitis and proctitis spans a time course that ranges from acute to chronic which require different management strategies. Patients can present with problems even after 30 years of being asymptomatic. • Colorectal cancer risk is increased with pelvic radiation and patients should be screened 5 years after completion of therapy. • Surgical treatment for radiation proctitis/colitis should be individualized and based on the clinical context of the patient as morbidity and mortality rates are high postoperatively. • Ischemic colitis represents the most common cause of gastrointestinal ischemia. The clinical picture has a wide spectrum ranging from mild cases with minimal mucosal ischemia to severe cases associated with transmural necrosis. Management and investigations need to be tailored depending on the clinical scenario encountered and patients require close vigilance by the surgeon.

Radiation Colitis Introduction An understanding of radiation injury to the colon and ­anorectal area is important for a coloproctologist. It is estimated that approximately 50 % of treatment protocols for cancer involve the use of radiation [1]. With malignancies such as anal cancer increasing, and a higher number of ­cancer survivors, the colorectal surgeon will continue to

encounter post-­radiation problems. The areas covered in this section consist of (1) pathogenesis, (2) prevention, (3) presentation, and (4) treatment. An important aspect to keep in mind while reading this section is the lack of high-quality evidence; an attempt has been made to provide the reader with recommendations based on the best evidence available.

Pathogenesis of Radiation Injury The two main forms of radiation delivery are external beam radiation therapy (EBRT) and brachytherapy [2]. External beam is what we encounter most and is delivered via linear accelerators which produce high-energy X-rays. The planning is typically done in three dimensions with CT (computed tomography) images. Gray (Gy) is the standard unit to indicate the amount of absorbed radiation. Fractionation refers to giving the total dose over multiple sessions—for example, 50 Gray of radiation could be given over 25 sessions with 2 Gy per session. Fractionation is done to minimize collateral tissue damage while maximizing tumor destruction. Conformal radiation refers to the use of metal plates (multileaf collimators) to bend the X-rays in order to target the tumor and minimize radiation to normal tissue. Brachytherapy refers to placement of the radiation source inside the body—i.e., beads or pellets. Radiation damage has been described through the “target cell” theory. This theory focused on the epithelium of the bowel and explained acute effects through the damage done to this layer which is rapidly proliferating. The delayed effects were explained by damage of other target cells such as endothelial cells or fibroblasts as their turnover is slower compared to intestinal epithelium. The main addition to this thinking is that other tissues/cells are part of the injury process [3]. Therefore, alterations to the gut microflora, immune system, microvasculature, and immune system are all thought to play a role in the symptoms induced by radiation [3].

© ASCRS (American Society of Colon and Rectal Surgeons) 2016 S.R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, DOI 10.1007/978-3-319-25970-3_54

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When radiation is used in the treatment of abdominal or pelvic malignancies, the colon and rectum are sometimes included in the field of radiation. As a result, injury can occur. As with other treatments, there are patient and “radiation” factors that can influence outcomes. Patient factors include Body Mass Index (BMI) with a higher BMI being protective. Smoking is a significant factor for worsening radiation-associated bowel complications [4], yet another reason to offer these patients a smoking cessation program. Additionally, previous surgery (fixing pieces of bowel in place—likely more relevant for small bowel injury), inflammatory bowel disease, diabetes, vascular and collagen vascular disease [3, 5, 6], and genetic predisposition are all predisposing factors [2]. The most important radiation factor is the dose. Other factors that play a role are the length of bowel radiated, fractionation, and use of chemotherapy [3]. Radiation effects can be considered acute or chronic. Acute symptomatology refers to those that occur during the actual treatment to 6 months after treatment is completed. Chronic radiation symptoms can continue on from the acute phase or after an asymptomatic period. Radiation symptoms can occur for up to 30 years after being latent; most patients will typically present with chronic changes 8–12 months after finishing their treatment [3, 7].

Prevention The first question then is can anything be done to prevent acute changes especially because there appears to be a higher rate of chronic problems in patients who experience severe acute proctitis. The absence of acute symptoms does not preclude chronic changes and symptoms from occurring [7–9]. This process of severe acute injury leading to chronic changes is termed the “consequential” late effect [9, 10]. Prevention can be divided into those related to radiation delivery and those that are not. The main goal with radiation delivery is to minimize damage to normal tissues surrounding the tumor. Conformal radiation therapy is one of the main methods of doing this. The 3D planning performed using CT and computer technology results in a higher dose of radiation delivery with less normal tissue being affected. Intensity-modulated radiation therapy (IMRT) is a technology whereby different intensities of radiation can be given (high and low) within the planned field. The neoplastic tissue is clearly identified as well as the normal tissue around it [11]. This modality has led to significant decrease in radiation toxicity and reduction in intestinal radiation during prostate cancer treatment even when compared to 3D planning/simulation [12]. In prostate cancer patients, acute and late radiation toxicity has also been reduced with the use of IMRT [13, 14]. In a study in prostate cancer, stereotactic radiation therapy has been found to cause lower rates of acute toxicity [14].

I. Raîche and H. Moloo

Brachytherapy, as mentioned previously, is when the source of radiation is implanted into the neoplasm (interstitial brachytherapy) or in a cavity which is close to the neoplasm (intracavitary brachytherapy). It can be used alone or with external beam radiation therapy and the goal again is to reduce normal tissue injury and is sometimes a good option for patients with inflammatory bowel disease [15, 16]. Proton beam radiation is an area where more research with respect to gastrointestinal toxicity is needed, but theoretically and with other tumors such as hepatocellular cancer the data looks promising [17]. The theory behind photon beams is that it “stops” in the target tissue and therefore collateral damage should be less. With respect to non-radiation delivery factors, patient positioning has been found to be an effective way of reducing radiation to rectal wall, small bowel, and bladder—i.e., prone, Trendelenburg [18]. Other strategies employ bladder distension, abdominal wall compression, and determining position based on pretreatment contrast studies [11, 19]. The Multinational association of Supportive Care for Cancer and International Society of Oral Oncology has recently written a good paper to guide clinical practice with respect to Gastrointestinal Mucositis secondary to radiation injury [20]. Intravenous amifostine and sulfasalazine orally have been recommended as preventative measures for radiation proctitis and enteropathy. The panel also “suggested” that probiotics containing Lactobacillus could be used to prevent diarrhea in patients being treated with radiation for a pelvic malignancy. It was also specifically recommended based on the best available evidence that 5-ASA and related agents such as mesalazine not be used to prevent diarrhea in patients receiving radiation for a pelvic neoplasm. They also recommended against using misoprostol suppositories to prevent acute proctitis from radiation. There are also operative maneuvers such as omental slings and tissue expanders that can be used to avoid radiation damage if it is planned post-resection.

Acute Radiation Colitis and Proctitis Radiation damages the mitotic activity that is occurring at the base of crypts, where stem cells. Reside therefore the cells that migrate to line the bowel are damaged leading to a suboptimal mucosal surface and mucosal inflammation [21]. This can lead to diarrhea because of the impaired absorption. The barrier to bacteria is also affected because of this process and bacteremia can result [8]. Motility is also affected through the creation of Giant Migrating Complexes and this goes back to normal after treatment is complete; during treatment it is thought this alteration contributes to the diarrhea and cramping experienced by patients; diarrhea is the most common acute symptoms experienced by patients [22]. Other acute symptoms include nausea, tenesmus, fatigue, and abdominal pain [3]. Nearly all patients (50–75 %) expe-

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rience symptoms in the acute period, but luckily these symptoms are usually self-limited. Consequently, treatment is usually supportive. Diarrhea, for example, can usually be controlled by antidiarrheal medications such as loperamide. Dietary modifications can sometimes help such as a lactosefree diet or one low in fat. Diarrhea that is severe can sometimes necessitate admission to hospital for intravenous hydration or parenteral nutrition. If first-line antidiarrheals such as l­operamide are not effective, octreotide can be used to slow diarrhea [23]. Suppositories with steroids can also be used. Butyrate enemas have been shown to help in the acute ­proctitis setting with the thought that supplying colonocytes with this short chain fatty acid nutrition will help resolve damage that has occurred [24]. With respect to nausea, antiemetics are usually effective. Nausea is usually an earlier symptom seen in the first week of radiation treatment versus diarrhea and abdominal pain are typically seen 2–3 weeks into treatment [3].

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because of the reaction of fibroblasts to cytokines, growth factors, and chemokines [2]. Atrophy results from the killing of cells and in concert with the other changes lead to malabsorption and strictures. The vascular damage from radiation can lead to dilation of small blood vessels—this is manifested as telangiectasias[2]. There can also be constriction of arterioles which leads to ischemia and in more severe cases necrosis; the fibrosis that occurs and which can progress over time can worsen the resultant ischemic injury [2, 3, 8]. The small vessel disease described is what distinguishes chronic from acute radiation changes.

Diagnosis

With an understanding of pathology, it is easier to understand chronic complications. Bleeding for example can be seen because of telangiectasias or ulcerations from ischemia. Malabsorption leading to diarrhea can be seen because of the atrophy of the mucosal lining or strictures leading to bacterial overgrowth. As mentioned earlier, radiation can also impact Chronic Radiation Colitis and Proctitis the nerves associated with gastrointestinal function and thereChronic symptoms and complications from radiation can fore accelerated small and large bowel motility can result range in severity but can be debilitating and significantly [23]. With worsening ischemic strictures can occur leading to affect the quality of life of an individual. The Radiation obstruction. With full thickness necrosis of the bowel wall, Therapy Oncology Group (RTOG) and the European fistulas or free perforation can result. Surgery is complicated Organization for Treatment and Research of Cancer by the fact that anastomotic leak rates are higher when irradi(EORTC) have devised a grading for late effects of radiation ated (with poorer blood supply) bowel is used [25]. with grades of 0–5. Zero represents the effect of radiation Diagnosis is usually done with endoscopy and the features that created no change compared to baseline and five is the seen correspond to the pathological changes—telangiectasias, effects that led to death (Table 54-1) [25]. atrophy, and friable tissue. Biopsies, if necessary, can rule out There is not a lot written specifically about radiation coli- processes such as inflammatory bowel disease, ischemic colitis. There are articles written regarding non-rectal radiation-­ tis, or drug-induced injuries. One should be cautious about induced injury. Based on these reports some predictions can taking biopsies in the radiated rectum as these have been be made regarding colitis. The most common symptom is implicated in a higher rate of fistula formation [27]. Histologic likely diarrhea. Patients can also present with more severe features of radiation therapy vary with the interval between symptoms such as obstruction or perforation. Determining completion of radiation treatment and onset of symptoms. specific complication rates regarding radiation colitis spe- Acute radiation injury (within 2–3 days after treatment) is cifically is difficult because studies that describe theses usu- characterized by surface epithelial damage, nuclear atypia ally include small intestine pathology as well [26]. with bizarre mitoses, attenuation and loss of crypts epitheThe symptoms of chronic radiation proctitis are outlined lium, increased apoptosis, and increased eosinophils with well in Table 54-1. The pathophysiology of these complica- eosinophilic crypt abscesses. In the chronic phase of radiation tions is related to ischemic injury. The main pathology relates injury, superimposed episodes of ischemia or the presence of to fibrosis, atrophy, and vascular damage. Fibrosis which mucosal or submucosal fibrosis can mimic primary acute or plays a prominent role in radiation injury is thought to occur chronic ischemic colitis. The distinctive features of chronic Table 54-1.  Late radiation effects on small/large intestine Grade 0 1 2 3 4 5

Symptoms None Mild diarrhea, mild cramping, bowel movement 5 times per day; slight rectal discharge or bleeding Moderate diarrhea and colic; bowel movement >5 times per day; excessive rectal mucus and intermittent rectal bleeding Obstruction or bleeding, requiring surgery Necrosis/Perforation, Fistula Death

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Figure 54-1. Radiation induced colitis. Colonic mucosa shows crypt distortion, crypt abscesses (thick arrows) and crypt atrophy, similar with inflammatory bowel disease. The crypt epithelium shows marked mucin depletion, regenerative nuclei and mitotic fig-

ures (thin arrow). Bizarre stromal fibroblasts and endothelial cells may be seen in lamina propria. Vascular injury may be also seen (not shown). Hematoxylin and eosin, ×100, ×200, ×4000. Reproduced with permission from Celia Marginean MD.

radiation injury include dilated, thickened, and hyalinized blood vessels, reactive or bizarre-­shaped endothelial cells, fibroblasts and myofibroblasts, and foamy cells within the arteries (obliterative arteritis) [8] (Figure 54-1).

through the MASCC guidelines for the treatment of chronic radiation injury in patients who are having rectal bleeding [20, 28, 29]. There is one trial that showed oral sucralfate was beneficial in helping with diarrhea [30]; however, in their examination of the evidence, the MASCC recently suggested that oral sucralfate not be used [20]. 5-ASA enemas have had mixed results and there is no clear evidence on whether it is beneficial for the treatment of chronic radiation proctitis or sigmoiditis and has been found to be harmful in some [31–33]. In the trial cited in the previous paragraph, it would seem that sucralfate is likely a more efficacious agent compared to 5-ASA [28]. Short chain fatty acid enemas still require further research prior to being able to recommend them as a treatment in chronic radiation proctitis [34]. Steroid enemas have also not been found to be consistently effective in the treatment of radiation proctitis [11, 23].

Management Treatment of chronic radiation injury to the colon and rectum can be divided into medical, endoscopic, or surgical.

Medications Medical treatment consists of topical versus systemic treatment. The main delivery method of topical treatment is via enema per rectum. Sucralfate enemas have been endorsed

54 Radiation, Microscopic, Ischemic Colitis

There is one trial that divided 60 patients into either a group that had betamethasone enemas, mesalamine orally, and metronidazole orally or a group that did not include oral metronidazole. In this trial it was found that bleeding and ulceration were lower in the group with metronidazole even up to 1 year [35] A topical treatment that has been shown to be effective in dealing with bleeding from chronic radiation proctitis is topical formalin therapy. The theory behind this is that the formalin is used to chemically cauterize the telangiectasias and ulcers that are bleeding. The two main methods of delivery are via irrigation of formalin or direct application of a formalin soaked gauze onto the mucosa usually via a rigid proctoscope—the concentration typically used is 4 % although there are papers that have utilized 10 % solutions [8, 36, 37]. After either method it is recommended that a washout of the formaldehyde is done. It should also be noted that multiple applications may be required to achieve high efficacy rates of around 80 % (and sometimes higher); those with severe proctitis or taking an antiplatelet agent may require more applications [36–38]. For example, in one study the average number of applications of direct application with a cotton swab via a proctoscope was 3.5 with 1.5 more applications for patients taking aspirin or with severe proctitis [37]. Another important aspect of this treatment is to avoid contact with the anoderm as formalin can be irritating to this area. The irrigation or direct contact is done during an application until it can be visualized that cauterization has occurred of the affected rectal mucosa. For irrigation with formalin, it can be done in small aliquots ranging from 20–50 cc up to a total volume of 400–500 cc [38, 39]. It is important to be cognizant of the potential complications which includes anal or pelvic pain, stricture, rectal wall necrosis, and fistula formation [36, 39]. Finally, there may be a higher complication rate in patients who have received radiation for anal cancer [40]. Other medical treatments include use of vitamins—one study of 20 patients with chronic radiation proctitis looked at vitamin E and C use and whether a variety of symptoms improved. There was significant reduction in bleeding, diarrhea, and urgency, but it is important to note that the authors felt that a proper randomized controlled trial was required to see if these vitamins have actual benefit [41]. Loperamide was also examined with a small randomized controlled trial with a total of 36 patients and was found to decrease diarrhea and transit time and increase bile acid absorption [42]. Hyperbaric oxygen therapy has reasonable evidence to support its use for radiation proctitis [43, 44]; this recommendation (support for its use) is one of the changes that has been made in the most recent MASCC guidelines [20].

Endoscopy Endoscopic therapy plays a role not only in the diagnosis of radiation injury to the bowel but can be used for treatment of it. With respect to bleeding, argon plasma coagulation (APC) likely plays the biggest role and for many would be the treat-

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ment of choice prior to using formalin. It is a safe and effective therapy with bleeding cessation in 80–90 % of cases. Its advantage is also related to the fact that it coagulates to a reliable superficial depth. As with formalin instillation, it can require multiple treatments. Not only has there been found to be a reduction in bleeding, but bowel function has improved as well. There are no randomized controlled trials examining this particular technology, but based on multiple retrospective studies it appears to be safe and efficacious [45–47]. One has to be careful to avoid the dentate line because it can cause pain. Complications are rare and typically consist of rectal pain and cramping. In one randomized trial comparing APC to formalin there was no difference in outcomes and both were found to be very effective in stopping bleeding (94 % APC and 100 % Formalin) [48]. In another randomized controlled trial with approximately 60 patients in each group, it was found that the addition of oral sucralfate to APC did not make a difference to the success rate of APC [49]. Historically, Nd:YAG laser therapy was used endoscopically, but with APC this is rarely used at present. In previous studies, it was found to be safe with rare complications of stricture, ulcers, fistula, and mucus discharge [50]. Another endoscopic technology that may find a wider application in the future is radiofrequency ablation as it can target a larger area and theoretically may have a lower stricture rate [51]. It is also important to remember that individuals who receive abdominopelvic radiation are at a higher risk of developing colorectal cancer. If there is not a reason to screen those patients earlier, they should d­ efinitely get surveillance done at 5 years post-completion of therapy.

Surgery Surgical treatment is required for patients whose symptoms cannot be managed with medical or endoscopic therapy and also for complications such as perforations, fistulas, or strictures/obstruction. For both patients and surgeons, surgery is not something to be taken lightly. Individualized management plans are likely required depending on the context of the patient and discussion with at least one colleague or at a multidisciplinary setting regarding the management is recommended. Luckily, only 10 % of patients require an operative intervention for colorectal complications post-radiation [52]. In any type of bowel resection, one needs to be aware that anastomotic leak rates are high when putting two pieces of radiated bowel together and is lower if only one of the pieces is irradiated [53]. Pelvic fistulas can be one of the difficult problems that surgeons can encounter post-radiation. Similar management principles can be employed as with other types of fistulas— i.e., management of any ongoing sepsis and trying to optimize the situation for healing (knowing of course that with irradiated tissue fistulas are more difficult to repair) through measures such as nutritional optimization. With many of these patients whether it is a rectovaginal or rectourethral fistula, diversion will likely be necessary. Surgery will then

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depend on factors such as how high the fistula is. Is it amenable to a perineal or abdominal approach and how will well-­ vascularized tissue be incorporated. The repair can therefore involve a flap reconstruction for a low rectovaginal fistula (i.e., gracilis or Martius) or a coloanal anastomosis with interposition of well-vascularized tissues such as omentum if it is a higher fistula. In the most severe cases, proctectomy or pelvic exenteration type procedures may be required. Diversion may be helpful in non-fistula cases as well. Studies have shown that a colostomy or ileostomy may resolve symptoms of pain, tenesmus, sepsis, incontinence, and obstruction and improve quality of life to the point where further surgical intervention may not be needed [52, 54]. Because dissection can be difficult in an irradiated pelvis, transverse and descending colostomies were found to be safer than a sigmoid colostomy [52]. Diversion does not always help with bleeding, but there has been at least one retrospective study that has shown improvement in bleeding with a stoma [55]. Overall, on a 30-year retrospective review (looking at colorectal surgery for radiation injuries), the approach— resection versus diversion versus bypass—did not lead to a difference in success. It is not surprising, considering that it was a retrospective review where the surgeons picked an operative approach based on what was most reasonable [54]. The promising finding was that 70 % of patients had symptomatic relief. Of the different indications fistula repair had the lowest success rate (55 %) compared to stricture (78 %), hemorrhage (64 %), and perforation (100 %). It is sobering to note that the morbidity rate was 65 % with a mortality rate of 7 % [54]. The conclusion of this 30 years review is that treatment plans should be highly individualized and this lesson is likely the one that the surgeon should remember when dealing with these patients.

Microscopic Colitis Introduction First described in 1976, microscopic colitis (MC) is an inflammatory colitis and a relatively common cause of non-­ bloody diarrhea [56, 57]. Two main types of MC have been described: collagenous colitis and lymphocytic colitis [58]. Although considered to be a milder disorder when compared to other inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease [58], MC can have a significant impact on patients’ quality of life [59, 60].

I. Raîche and H. Moloo

and believed to be present in 10–30 % of patients older than 70 investigated for chronic diarrhea and presenting with a normal colonoscopy [58, 61, 62]. Collagenous colitis is more common in women, while lymphocytic colitis is equally distributed between genders [63, 64]. Relative incidence of collagenous vs. lymphocytic colitis varies between series; in a recent report, it was estimated that the prevalence of collagenous colitis was 39.3 per 100,000 persons vs. 63.7 for lymphocytic colitis [62, 63].

Etiology and Risk Factors The cause of MC remains unknown; it is hypothesized to be multifactorial [65].

Genetics A limited number of Familial cases of MC have been reported [62]. It is interesting to note that members of the same family can develop either collagenous or lymphocytic colitis [66]. An association has been found with HLA-DQ2 and TNF2 allele carriage and microscopic colitis suggesting a possible association with the pathogenesis of coeliac disease [67, 68]. On the other hand, NOD2/CARD15 gene, known to be linked to Crohn’s disease susceptibility, was not found to be more frequent in MC patients compared to healthy controls [69]. MMP-9, another marker of inflammatory bowel disease, has been found more frequent in MC patients, but MMP 1 and 7 were not found to be associated with MC [70].

Infection Stool cultures are negative in most patients with MC. However, onset after infection with Yersinia enterocolitica, Clostridium difficile, and Campylobacter jejuni has been described [58].

Smoking In case–control study, smoking has been associated with an increased risk of MC (OR 2.12) [71]. In a retrospective review of 184 patients, smokers tended to develop symptoms earlier in their life: in one study the mean age at onset of diarrhea was 50.4 years old vs. 65.5 in the nonsmoking group. In the same study, smoking habits were not associated with increased risks of relapse [72].

Epidemiology The incidence of microscopic colitis is increasing [61–63]. In 2001, the estimate prevalence in the United States was 103 cases/100,000 persons [63]. It has been found in all age groups; however, it is more common in the older population

Medications Evidence regarding the association between MC and medications is equivocal. Some studies suggest a link between MC and nonsteroidal anti-inflammatory drugs (NSAIDS),

54 Radiation, Microscopic, Ischemic Colitis

HMG-CoA reductase inhibitors (statins), proton pump inhibitors (PPI), and selective serotonin reuptake inhibitors (SSRI), while others did not find a similar association [64, 73]. Some classes of drugs potentially linked to MC such as NSAIDS and PPI are known to cause watery diarrhea as a common side effect confounding the potential causal relationship. Because they can exacerbate symptoms of a preexisting MC, further investigations may be prompted and lead to an MC diagnosis [74].

Autoimmunity In a recent survey of 116 patients with MC, 30.4 % had an autoimmune condition [75]. Some diseases have a particularly strong association: celiac disease and thyroid disease. Other conditions that have been linked to MC include diabetes mellitus, arthritis, alopecia, psoriasis, and Sjögren’s syndrome [75]. In contrast to Crohn’s and ulcerative colitis, no association has been found with autoimmune liver conditions [58].

Clinical Manifestations Clinical Presentation Chronic, non-bloody, watery diarrhea is the hallmark of this disease [62]. It can occasionally lead to fecal incontinence, especially in the elderly. In a retrospective cohort study, fecal incontinence was present in 25 % of patients [76]. Watery diarrhea, even during flare-ups, rarely leads to dehydration [65]. Bile salt malabsorption can make diarrhea worse and therefore cholestyramine is sometimes used for treating these patients [77]. Weight loss is also common, being found in 41–46 % of patients [64, 76]. Abdominal pain is more common in MC patients compared to controls. Interestingly, patients considered to be in remission also have more abdominal pain compared to healthy control [65]. Fatigue is another frequent complaint of patients with MC, present in 50–60 % of patients; it is unclear if it is due to nocturnal diarrhea preventing rest or to the disease itself [58, 65]. Lymphocytic and collagenous colitis cannot be differentiated based on clinical presentation [62]. Interestingly, the pathologic abnormalities found in MC have been found in asymptomatic and constipated patients [65].

Complications MC rarely leads to complications [62]. Cases of spontaneous perforation have been reported, but it is more common for perforation to occur as a result of a colonoscopy [78, 79]. “Fractured colon” associated with linear ulceration developing during colonoscopy has been described in collagenous colitis [80]. Collagenous deposition on the wall of colon is

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thought to render the wall less pliable and more likely to “fracture” during colonoscopy [81]. MC has not been found to be associated with an increased risk of colorectal cancer in a retrospective analysis of 547 MC cases [82]. A recent case–control study of 647 patients with MC followed for an average of 4.63 years found that MC was associated with a lower risk of colon cancer or adenomatous polyps [83].

Diagnosis Histopathology is the mainstay of the diagnosis of MC. Because of the nonspecific clinical presentation the differential diagnosis is wide and includes inflammatory bowel disease, infectious colitis, medication-induced changes, celiac disease, bile salt malabsorption, lactose malabsorption, and irritable bowel disease [62, 84]. Colonoscopy with two or more biopsies in each of areas of the ascending, transverse, descending, and sigmoid colon respectively is the exam of choice to diagnosis MC. Biopsies should be sent separately [85]. The pathologic findings tend to be patchy involvement occurring anywhere in the colon; however, the disease is classically more severe in the right colon [84, 86]. Up to 30 % of rectal biopsies are normal in patients with MC, underscoring the need to obtain biopsies throughout the colon. MC was originally described in patients with a normal endoscopic exam and most patients with MC do have a normal exam. However, endoscopic abnormalities have been described in a small number. In a recent literature review of 42 articles (total number of patients included not mentioned), 88 patients with abnormal colonoscopy and a diagnosis of collagenous colitis were found. The most frequent findings were mucosal nodularity, alteration of the vascular pattern, and mucosal defects [87]. Pathologic findings of collagenous colitis include preserved crypt architecture and expanded lamina propria by a mixed inflammatory infiltrate, including plasma cells, eosinophils, and occasional neutrophils, mostly on the superficial portion underneath the surface epithelium. The crypt epithelium shows regenerative nuclear changes. Focally the subepithelial collagen layer is thickened, which is the main diagnosis feature, has a lacy appearance, and incorporates inflammatory cells and small capillaries. The surface epithelium shows markedly increased intraepithelial lymphocytes and focally may be detached from the mucosa. The pathologic findings of lymphocytic colitis include preserved crypt architecture and expanded lamina propria by numerous plasma cells, lymphocytes, and eosinophils. The surface and crypt epithelium are diffusely infiltrated by numerous T ­lymphocytes (diagnostic if >20 IELs per 100 epithelial cells), which by immunohistochemistry express CD3 and CD8 and lack CD4. The crypt epithelium shows hyperchromatic, regenerative nuclei (Figures 54-2 and 54-3).

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Figure 54-2. Collagenous colitis. (a) Colonic mucosa shows preserved crypt architecture. The lamina propria is expanded by a mixed inflammatory infiltrate, including abundant plasma cells admixed with eosinophils and occasional neutrophils, mostly on the superficial portion underneath the surface epithelium. The crypt epithelium shows regenerative nuclear changes. On several areas, the epithelial collagen layer is moderately thickened. Focally, the collagen band has a lacy appearance and incorporates inflammatory cells and small capillaries. The surface epithelium shows markedly increased ­

i­ntraepithelial lymphocytes and focally is detached (split) from the mucosa. Hematoxylin and eosin, ×100. (b) Thick subepithelial collagen layer, incorporating microcapillaries and inflammatory cells (thick arrows). Hematoxylin and eosin, ×200. (c) Thick subepithelial collagen layer, incorporating microcapillaries and inflammatory cells, with splitting of the surface epithelium (thin arrow). Hematoxylin and eosin, ×200. (d) Thick subepithelial collagen layer (blue), incorporating microcapillaries and inflammatory cells. Masson trichrome stain, ×200. Reproduced with permission from Celia Marginean MD.

Figure 54-4 presents an algorithm to illustrate pathologic diagnosis of MC. The term incomplete MC is used when a patient has pathological alterations not meeting the criteria for MC [85, 89]. A study conducted to assess observer variability in the diagnosis of MC found a high intra-observer and interobserver reliability for assessment of samples containing normal colon, inflammatory bowel disease samples, and MC samples. The reliability assessment for differentiat-

ing collagenous and lymphocytic colitis was lower but still good (κ = 0.64–0.70 for types of MC vs. κ = 0.84–0.86 for diagnosis of MC) [89]. Laboratory analysis usually shows nonspecific abnormalities such as mildly elevated inflammation markers. Fecal calprotectin and lactoferrin are not consistently elevated ­ (in contrast to inflammatory bowel disease), limiting their use in the diagnosis of MC [90]. Research to identify reliable

54 Radiation, Microscopic, Ischemic Colitis

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Figure 54-3. Lymphocytic colitis. (a, b) The colon shows preserved crypt architecture. The lamina propria is markedly expanded by numerous plasma cells, lymphocytes, and eosinophils (thick arrow). The surface and the crypt epithelium are diffusely infil-

trated by numerous lymphocytes (thin arrow). The surface and crypt epithelium shows hyperchromatic, regenerative nuclei. Hematoxylin and eosin, ×40, ×100, ×200. Reproduced with permission from Celia Marginean MD.

Patient with watery diarrhea

Normal colonoscopy

Abnormal biopsy signs of chronic inflammattion

Abnormal crypt architecture

Minimal change colitis

Normal crypt architecture

Increased number of intraepithelial lymphocytes

Thick subepithelial collagenous plate

Lymphocytic colitis

Figure 54-4.  Algorithm for pathological diagnosis. Adapted from Warren, Edwards & Travis, 2002 [86].

Collagenous colitis

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biomarkers is ongoing [58, 65]. Imaging is typically normal and does not have a role in the diagnosis of MC [58].

Management There is no curative treatment for MC. The goal of the treatment is to control the symptoms. In 2009, after conducting multiple surveys, Hjortswang et al. published criteria to define clinical remission based on the impact of the symptoms on patient quality of life. According to their work, patient with a mean of 85 % in both groups, with a 13 % relapse rate in the remission group at 2 years. There was no placebo arm in this study [97].

Immunosuppressive and Anti-TNF Medications This class of medication is generally reserved for patients refractory to other types of medical management because of their potential side effects. The role of azathioprine and mercaptopurine in budesonide refractory MC was studied through a retrospective review of 46 patients. Overall, thiopurines achieved remission in 41 % of patients; side effects included elevated liver enzymes and nausea/vomiting [98]. The evidence supporting the use of methotrexate in budesonide refractory MC is conflicting with one study reporting a clinical response in 16 of 19 patients and another study showing no improvement in nine patients [99, 100, 102]. Small series (less than ten patients) refractory to standard medical management report symptom improvement with the use of antiTNF medication [103–104]. Larger studies are needed to better define the role of immunosuppressants in MC.

Bismuth Subsalicylate Bismuth subsalicylate has been widely used, but there is limited evidence to support its use. A recent Cochrane review found only one partially published trial on b­ ismuth subsalicylate including nine patients [105]. It was found to induce remission in 100 % of patients at a dose of 262 mg, eight tablets divided into three doses for 8 weeks [84]. The same authors published a 13-patient series with a response rate of 85 % and a 7 months r­ emission in 69 % of patients [106]. Interestingly, b­ ismuth subsalicylate has been found to be useful in treating chronic intractable diarrhea in up to 74 % of patients in a 31-patient case series [107].

Cholestyramine and Loperamide Antidiarrheals are often recommended as the first line of treatment. They seem to have the most benefit in patients with mild symptoms. They are unlikely to induce a pathologic response and the long-term efficacy has not been proven. Patients with MC not responding to budesonide or recurring symptoms after multiple cycles of treatment should be tested for bile salt malabsorption; affected patients could benefit from cholestyramine [58, 62, 65].

Other Medications Many other medications have been used to treat MC. Boswellia serrata extract and probiotics were not associated with a statistically significant response to treatment [94]. Antibiotics such as metronidazole and erythromycin have been used, but their effects have not been formally studied [65].

54 Radiation, Microscopic, Ischemic Colitis

Surgery Surgery has a limited role in the treatment of MC. Loop ileostomy, subtotal colectomy, and proctocolectomy with J-Pouch have been described to treat severe intractable disease [108, 109]. Indications for surgery are ill defined and likely to be less frequent as our understanding of the optimal medical regimen improves [58, 62, 65].

Ischemic Colitis

961 Table 54-2.  Pharmacologic agents in order of evidence strength [111, 116] Moderate evidence (further research would like have an impact on authors’ confidence in the estimate effect) Low evidence (further research is expected to have an important impact on authors’ confidence in the estimate effect)

Introduction The term ischemic colitis was coined by Martson and published for the first time in 1966 [110]. Colon gangrene had been recognized since the late 1800, but the physiopathology of the disease had remained unsolved until the mid-twentieth century [113]. Ischemic colitis (IC) can be defined as “the condition that results when blood flow to the colon is reduced to a level insufficient to maintain cellular metabolic function” [111]. It is a fairly common disease usually self-­limited. Affected patients are often frail which explain the relatively high rate of mortality associated with this disease [112].

Anatomy and Physiology Branches from the superior mesenteric artery and the inferior mesenteric artery supply the colon. Splanchnic vessels are amongst the most reactive in the body, with blood flow varying from 10 to 35 % of cardiac output depending on physiologic or pathologic conditions [112]. This characteristic partially explains the high frequency of a low flow state in the colon. Two watershed regions have been described in the colon where ischemia is most likely: the splenic flexure (area of Griffith) and the recto-sigmoid junction (Sudeck’s point) [113]. This is superimposed on the fact that the colon receives the least amount of blood flow in the gastrointestinal tract as measured by blood flow to 100 g of tissue [113].

Epidemiology and Risk Factors The incidence of IC varies between 4.5 and 44 cases per 100,000 person-years. It is the most frequent site of gastrointestinal ischemia [113]. It is more common in females and in patients over the age of 65 [114]. It is recognized as a disease affecting older, comorbid patients. Chronic obstructive pulmonary disease, thrombophilia, history of irritable bowel disease, constipation, diabetes, renal failure, hypertension, extreme exercise, myocardial infarction, and history of vascular disease have been identified as risks factors [111, 114, 115]. Multiple drugs are known to increase the risks of developing colonic ischemia—a literature review published in 2007 documented drug classes having been linked with development of ischemic colitis [116] (Table 54-2).

Very low evidence (estimate effect is uncertain)

Constipation-inducing medications Immunosuppressive agents Illicit drugs Antibiotics Appetite suppressants Chemotherapeutic agents Decongestants Diuretics Ergot alkaloids Hormones Laxatives Psychotropic medications Digitalis Satins Nonsteroidal anti-inflammatory agents Serotonin agonists/antagonists Vasopressor

There is a classic association between ischemic colitis and AAA repair. A review of 89,967 patients undergoing AAA repair showed a global incidence of ischemia of 2.2 %. The type of repair performed correlated with the incidence of IC. Almost 9 % of ruptured AAA repair were complicated by IC in contrast to 1.9 % of open elective procedures and 0.5 % of endovascular repairs [117]. Following all types of AAA repair, IC was associated with a mortality of 37.8 % vs. 6.7 % for the patients without this complication. With ischemic colitis being so frequent after ruptured AAA, it has been suggested by some that routine sigmoidoscopy could be beneficial in this patient population. In a prospective trial of 161 patients only one-third of patients found to have IC on routine endoscopy developed symptoms [118]. Importantly, routine use of colonoscopy has not been shown to improve patient outcomes and therefore is not recommended [111, 119]. The first manifestation of ischemia in a postoperative patient is often rectal bleeding, generally happening in the first 48 h after surgery. These patients should be investigated with endoscopy [115]. In patients requiring surgery, anastomosis should be avoided to minimize the risk of graft contamination [120].

Pathophysiology Mechanisms of ischemic colitis can be divided into non-­ occlusive arterial ischemia, embolic or thrombotic arterial occlusion, and mesenteric vein thrombosis. The mucosa is the first layer of the bowel to show ischemic changes, after which if there is a progression all layers of the bowel wall can be involved. Because it is furthest from the mesentery, the antimesenteric part of the bowel is affected first [111]. Transient mucosal damage can be seen after 20 min to 1 h of insufficient blood flow with transmural changes occurring after 8–16 h [121, 122].

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Non-occlusive Ischemia Non-occlusive ischemia is responsible for 95 % of IC cases [120]. Non-occlusive ischemia can be idiopathic without identifiable cause or may be secondary to a medical or surgical condition diminishing colonic blood flow [111]. Colorectal vascular anatomy explains why IC happens on the left side of the colon in >75 % of cases but affects the rectum in only 5 % of patients [116, 117]. When the ascending colon is diseased, the cecum is the most frequently affected colonic segment [112]. Colonic injury and the systemic response to IC are due to both the hypoxic state and reperfusion injury [115]. Most of the evidence presented in the chapter is based on the management of this type of IC.

Arterial Thrombosis and Emboli Related Ischemia An embolic source of ischemia is a less frequent cause of colonic ischemia. It is often seen with concomitant small bowel ischemia and the distribution is less likely to follow the zones of watershed area. In a case–control study on 60 patients with segmental non-transmural ischemia, patients with IC were 2.5 times more likely to have a cardiac source of embolism than control patients with similar comorbidities and medications but without IC. Thirty-two percent of patients were placed on anticoagulation and 25 % on antiarrhythmic therapy after cardiac work-up including transthoracic echocardiogram, electrocardiogram, and rhythmic Holter monitoring [112, 123].

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vomiting, abdominal distension, diarrhea, dizziness, and syncope [125]. Right-sided colitis is less likely to be associated with rectal bleeding and this diagnosis should be kept in mind in patients with isolated right-sided abdominal pain [111]. IC can evolve from an acute reversible colopathy (70 %) into different clinical patterns including gangrene (10 %), chronic colitis (18 %), and fulminant colitis (2 %) [126, 127]. Strictures form in 3.3–9.4 % of patient—they are asymptomatic in the majority of cases [111].

Diagnosis Laboratory Studies Results from laboratory studies are often nonspecific. Increased white blood count and acidosis are associated with infarction. There is no reliable marker of ischemia. Increased lactate, LDH, CPK, or amylase can sometimes indicate tissue damage [120]. Stool culture should be sent in patients with uncertain diagnosis. Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157:H7, and parasites can cause a similar clinical picture. C. difficile should be considered even though it is usually not associated with bloody diarrhea [119]. Klebsiella oxytoca has been found in patients with right-sided hemorrhagic colitis mimicking ischemic colitis. It has been found more commonly in patients exposed to penicillin derivatives [128, 129].

Imaging

Venous Thrombosis

Plain films and contrast enema

Venous thrombosis is more frequently related with small bowel ischemia; and it is the rarest cause of IC [113]. It tends to affect the ascending colon more frequently than the descending. The management of this entity is usually nonoperative : systemic anticoagulation and occasional catheter-­ directed thrombolysis are typically used to improve the situation. A new entity, mesenteric phlebosclerotic colitis, has been described in 2003. Its etiology is still unknown. Patients present with abdominal pain, mesenteric venostasis, and fibrotic and calcified veins. The optimal management of this condition remains to be defined, so far it has been mostly surgical for severe cases [114].

In IC, plain abdominal films can be normal or show nonspecific findings of distention and ileus. Free air can be seen with perforation. Classic findings of bowel ischemia (i.e., thumbprinting and pneumatosis) are present in 21–30 % of plain films in patients with IC [111, 120]. Contrast enemas have a limited use in the acute phase as they may make ischemia worse by increasing intraluminal pressure. Contrast studies can be used after the acute process has resolved to assess stricture formation [115].

Clinical Presentation Abdominal pain and rectal bleeding are the most frequent symptoms associated with acute IC [125]. Nine to twenty-­four percent of lower GI bleeds are caused by ischemic colitis [111]. In a review of 401 IC cases, 5 % required a blood transfusion [125]. Abdominal pain is usually combined with an urgent desire to defecate [115]. Other symptoms include nausea,

Abdominal CT scan CT scans are frequently performed in the Emergency Room to evaluate patients with abdominal pain; CT scan with intravenous contrast is currently the imaging modality of choice to assess IC [111]. The accuracy of CT scan in determining bowel ischemia varies between 74 and 79 % depending on the study protocol and the experience of the radiologist [130]. In a recent review of CT imaging at different clinical phases during ischemia, 100 % of patients presenting in the acute phase had a radiologic abnormality, most frequently pericolonic fluid and free fluid, change in bowel wall densities, and

54 Radiation, Microscopic, Ischemic Colitis

bowel wall thickening [131]. Pneumatosis was present in 1,200 – 1,500 mL / day

Fluid, electrolyte, and nutritional support

Treatment

Oral rehydration solution

Dietary changes: Small frequent meals, separate liquids and solids, sip liquids, avoid concentrated sweets, try naturally thickening foods

Supplemental IV fluids

Psyllium husk: 1 tablespoon mixed with water PO two or three times daily

Parenteral nutrition

Loperamide: 2–4 mg PO 30 minutes before meals and bedtime

Diphenoxylate/atropine tablets (2.5 mg /0.025 mg): 1–2 tabs PO 30 minutes before meals and bedtime

Paregoric (camphorated tincture of opium): 2–4 mg PO every 6 hours

Anti-secretory therapy with H2- blocker or proton pump inhibitor

Total bowel rest + TPN Consider novel hormonal agents

Figure 55-26. Proposed management algorithm for management of high output small bowel stomas.

Outputs between 1200 and 1500 mL/day are borderline high and may cause problems for some ostomates. Persistently high stoma outputs can be treated with dietary, behavioral, and medical means via a proposed algorithm described in Figure  55-26. Behavioral alterations include avoidance of large bolus feedings in lieu of smaller, more frequent aliquots. Large meals can be replaced with smaller frequent meals, fluids can be sipped rather than gulped, and solids and liquids can be consumed at different times to minimize bolus effects. Concentrated sweets including juice, soft drinks, and candy should be limited to decrease the effects of osmotic diarrhea. Breads, crackers, peanut butter, and bananas may naturally thicken stoma outputs and help decrease volumes. The addition of psyllium powder mixed in water helps to absorb excess fluid from the intestinal tract and thicken outputs. Hypotonic oral fluid restriction (500–1000 mL/day) and treatment with the cheap and easily made World Health Organization oral rehydration solution (Table 55.3) [82] help limit sodium loss and may produce a more favorable osmotic intestinal gradient [81]. It has been shown that most high output patients can avoid IV fluid and electrolyte supplementation if oral intake is restricted to 500–1000 mL/24 h of oral rehydration solution [83].

Table 55-3.  Oral rehydration solution Ingredients – 3/8 tsp salt (sodium chloride) – ¼ tsp table salt substitute (potassium chloride) – ½ tsp baking soda (sodium bicarbonate) – 2 tbsp + 2 tsp sugar (sucrose) – Add tap water to make 1 l – Optional: Nutrasweet® or Splenda® based flavoring of choice, to taste Directions: Mix dry ingredients with water and serve. Best sipped slowly over long periods of time Contains 27 g of sucrose, 70 mEq/L of sodium, 20 mEq/L of potassium, and 30 mEq/L of bicarbonate. The final osmolarity is approximately 245 mOsm/L tbsp tablespoon, tsp teaspoon

Following dietary and behavioral changes, pharmacotherapy may be required to manage high output stomas. Medical therapy typically begins with stepwise titration of antimotility agents beginning with loperamide and adding diphenoxylate/atropine. It is useful to take such antimotility agents approximately 30 min before meals (three times daily) to preemptively slow transit time before eating. Rarely, intestinal transit may be so rapid that tablet medications do not have enough time to completely dissolve, leaving elixir forms of antimotility agents preferable. Anti-secretory therapy with either H2 or proton bump blocking agents may be added to decrease stoma outputs by reducing gastric secretions. If dietary, anti-secretory, and antimotility therapies fail, oral opium tincture (Paregoric, camphorated tincture of opium) or oral codeine phosphate can be added. Paregoric can be costly and can cause sedation and is typically added as a later measure for recalcitrant high output stomas. Common medicines to manage high output stomas are detailed in Table 55.4. Unexpected and persistently high stoma outputs merit a work-up to exclude other potentially treatable causes. Cross-­ sectional abdominal imaging or a small bowel fluoroscopic series should be performed to exclude a partial bowel obstruction, which can cause paradoxically high outputs. High outputs can be caused by small bowel Crohn’s disease, which can be evaluated with small bowel enteroscopy through the stoma or cross-sectional imaging. Clostridium difficile enteritis is a reported cause of both small and large bowel high output stomas and can be evaluated with stool testing. Steatorrhea may develop in patients with significant ileal resections and can be treated with oral cholestyramine. Pancreatic insufficiency may rarely cause persistently high stoma outputs and can be remedied with a trial of pancreatic enzyme replacements. During periods of high stoma outputs, fluid, electrolyte, and nutritional support may be necessary. Periodic surveillance of serum electrolytes, daily weights, and strict recording of inputs and outputs guide resuscitation and replacements. Short gut situations with a high jejunostomy may not respond to standard therapies and may require parenteral fluids or nutrition. On rare occasions with critically proximal stomas, patients may require fasting and total parenteral nutrition as a last resort to sustain euvolemia.

55. Intestinal Stomas

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Table 55-4.  Common medicines for control of high output stomas Medication

Starting dose

Maximum daily dose

Psyllium Loperamide tab Loperamide liquid Diphenoxylate-atropine tab Diphenoxylate-atropine liquid Codeine tab Codeine elixir Paregoric 0.4 mg morphine/1 mL Paregoric (45 % alcohol) Opium tincture 10 mg morphine/1 mL opium (19 % alcohol)

1 tablespoon BID 2–4 mg PO QID 2–4 mg PO QID 2.5–5 mg PO QID 2.5–5 mg PO QID 15–30 mg PO QID 15–30 mg PO QID 5 mL PO QID 0.3–1 mL PO QID

1 tablespoon TID 16 mg (4–8 tabs) 80 mL (16 mg) 20 mg (4–8 tabs) 40 mL (20 mg) 240 mg (60 mg PO QID) 240 mg (80 mL) 37.5 mL PO QID (150 mL/day) 1.5 mL PO QID (6 mL/day)

Adapted from Parekh and Seidner [3]

Octreotide, a somatostatin analogue; teduglutide, a glucagon-­ like peptide 2 analogue; and human growth hormone all show promise in managing the most recalcitrant high output stoma associated with short gut syndrome [84, 85].

Stoma Reversal Preoperative Preparation The surgeon should have a clear understanding of the patient’s anatomy prior to attempting stoma reversal. For patients with a stoma created by another surgeon, it is crucial to review the prior operative and pathology reports to understand the surgical indications, encountered pathology, and remaining anatomy. Record review is particularly important when reversing an end colostomy performed for diverticulitis or malignancy, since additional resection of the distal stump, descending colon, and splenic flexure mobilization may be needed to complete an adequate resection. Close or threatened margins found on oncologic pathology reports may merit endoscopic anastomotic evaluation to exclude cancer recurrence prior to stoma reversal. Endoscopic mucosal evaluation may be helpful prior to reversing stomas in IBD, ensuring that disease activity is controlled in the defunctioned bowel before attempting reversal, but the endoscopist must be aware that diversion colitis may grossly and histologically mimic IBD [86]. If a diverting loop stoma was used to protect a distal anastomosis, the authors prefer to use a lower gastrointestinal fluoroscopic contrast study to exclude anastomotic leak, stricture, and obstruction prior to stoma reversal. Similarly, for patients undergoing reversal of an end stoma, preoperative fluoroscopic and endoscopic studies are important to evaluate the remaining anatomy and quality of both distal and proximal segments of bowel—particularly when reversing another surgeon’s stoma. Fluoroscopic abnormalities can be further examined with endoscopy allowing mucosal evaluation, tissue sampling, and anastomotic dilation, if needed. Coloanal, distal colorectal, and ileal pouch-anal anastomoses may be additionally assessed and gently dilated with digital rectal exam. Several groups espouse selective, rather than routine,

use of lower GI contrast studies for anastomotic evaluation prior to stoma reversal and note that most anastomotic ­complications can be diagnosed without imaging [87–91]. Although intra- and postoperative surprises are not completely avoidable, the authors feel preoperative evaluation including record review, imaging, and endoscopy is the best way to avoid unexpectedly complex stomal reversals.

Timing Timing of stoma reversal may impact the ease of the procedure. Diverting loop stomas are typically reversed within 2–3 months after creation once the surgeon is satisfied with the distal anastomosis (or pathology) that required diversion. Limited evidence suggested that loop ileostomy reversal performed less than 8.5 weeks following coloanal or ileoanal anastomosis may be associated with increased risk of complications [92]. Recently, several small studies have challenged this notion. A Turkish study showed that 88 % of loop ileostomy patients could be reversed during the same admission as the index operation without increasing morbidity, whereby avoiding high rates of stoma-related complications [93]. Nineteen patients undergoing loop ileostomy reversal within 10 days of the index operation revealed increased rates of wound infections, but otherwise similar complication profiles compared to normal interval closure patients [94]. Another retrospective study revealed patients who underwent loop ileostomy reversal less than 12 weeks from the interval operation had less postoperative nausea and vomiting than patients closed after 12 weeks [95]. Results from a Scandinavian prospective randomized trial comparing loop ileostomy reversal at 2 versus 12 weeks after low anterior resection are in press at the time of this publication and are eagerly awaited to provide evidence-based guidance to surgeons [96]. Until more rigorous evidence is available supporting safe early closure, the authors recommend loop ileostomy closure at approximately 8–12 weeks postoperatively as dictated by the clinical situation. The use of adjuvant chemotherapy introduces another consideration in the timing of stoma reversal. If adjuvant chemotherapy is planned, conventional wisdom dogmatically

996

dictates keeping a diverting stoma through the duration of treatment to minimize postoperative reversal complications and diarrhea. Conversely, chemotherapy may further compound dehydration resulting in readmission for up to 11 % of ileostomy patients [97] and ostomates must be monitored carefully for dehydration during chemotherapy. A recent small retrospective review showed that loop ileostomy reversal in the midst of colorectal cancer chemotherapy had comparable morbidity and cancer-related outcomes in select patients compared to post-chemotherapy reversal [98], although this practice is not widely adopted at this time. Patient choice plays a large role in this situation, and a thorough discussion is helpful in choosing the ideal time for stoma reversal. The optimal time for end stoma reversal remains a contentious issue with conflicting guidance in the literature [99]. It is generally considered that early postoperative adhesions become less tenacious and vascular with time, which may ease a challenging intra-abdominal dissection. Retrospective comparisons between early (15 weeks) end colostomy reversal detail similar morbidity, but increased length of stay, subjective adhesion density scores, and small bowel injuries favoring later surgery [100]. An older study associated early Hartmann’s reversal (