Schwartz's Principles of Surgery, 8th Edition

Schwartz’s Principles of

Surgery

i

NOTICE Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The editors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the editors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.

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Schwartz’s Principles of

Surgery Eighth Edition Editor-in-Chief

F. Charles Brunicardi, M.D., F.A.C.S. DeBakey/Bard Professor and Chairman Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Associate Editors

Dana K. Andersen, M.D. Harry M. Haidek Distinguished Professor and Chairman Department of Surgery University of Massachusetts Memorial Medical School Worcester, Massachusetts

Timothy R. Billiar, M.D. George Vance Foster Professor and Chairman of Surgery Department of Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

David L. Dunn, M.D., Ph.D. Jay Phillips Professor and Chairman Department of Surgery University of Minnesota Medical School Minneapolis, Minnesota

John G. Hunter, M.D., F.A.C.S. Professor and Chairman Department of Surgery Oregon Health & Science University Portland, Oregon

Raphael E. Pollock, M.D., Ph.D., F.A.C.S. Head, Division of Surgery Professor and Chairman Department of Surgical Oncology Senator A.M. Aiken, Jr., Distinguished Chair The University of Texas M.D. Anderson Cancer Center Houston, Texas

Illustrations by Philip Ashley & Associates McGRAW-HILL MEDICAL PUBLISHING DIVISION New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto

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Schwartz’s Principles of Surgery, Eighth Edition C 2005, 1999, 1994, 1989, 1984, 1979, 1974, 1969 by Copyright  The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher.

1 2 3 4 5 6 7 8 9 0 DOWDOW 0 9 8 7 6 5 4 ISBN: 0-07-141090-2 This book was set in Times Roman by TechBooks. The editors were Marc Strauss, Michelle Watt, and Nicky Fernando. The production supervisor was Catherine H. Saggese. The cover designer was Aimee Nordin. The index was prepared by Jerry Ralya. RR Donnelley was the printer and binder. This book is printed on acid-free paper.

Library of Congress Cataloging-in-Publication Data Schwartz’s principles of surgery / edited by F. Charles Brunicardi . . . [et al.]. – 8th ed. p. ; cm. Rev. ed. of: Principles of surgery / editors, Seymour I. Schwartz . . . [et al.]. 7th ed. 1999. Includes bibliographical references and index. ISBN 0-07-141090-2 1. Surgery. I. Title: Principles of surgery. II. Brunicardi, F. Charles. III. Schwartz, Seymour I., 1928-IV. Principles of surgery. [DNLM: 1. Surgery. 2. Surgical Procedures, Operative. WO 100 S399 2005] RD31.P88 2005 617–dc22 2003070716

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To my wife, Melissa, my children, Isaac and Jackson, my mother, Rose, and my late father, Edward Brunicardi, for their love and support. F.C.B. To my wife, Cindy, and my children, Ashley, Lauren, Kathryn, Thomas, and Olivia. D.K.A. To my father, Robert R. Billiar, D.V.M., my first role model for professional excellence. T.R.B. To the outstanding students and teachers of the discipline of surgery at the University of Minnesota—past, present, and future. D.L.D. To my wife Laura, my children, Sarah, Sam, and Jillian, and the residents, fellows, and surgical faculty at OHSU who have created a community of health, collegiality, and open minded intellectual rigor. J.G.H. To my children, Samuel and Jessica Pollock, and my late father. R.E.P.

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Contents

Contributors

ix

Foreword

xvii

Preface

xix

Preface to the First Edition

xxi

PART I Basic Considerations 1

2

3

4

5

Systemic Response to Injury and Metabolic Support Edward Lin, Steven E. Calvano, and Stephen F. Lowry Fluid and Electrolyte Management of the Surgical Patient Rosemary A. Kozar and Frederick A. Moore Hemostasis, Surgical Bleeding, and Transfusion David Schwartz, Karen L. Kaplan, and Seymour I. Schwartz Shock Andrew B. Peitzman, Brian G. Harbrecht, and Timothy R. Billiar

Cell, Genomics, and Molecular Surgery 401 Xin-Hua Feng, Jeffrey B. Matthews, Xia Lin, and F. Charles Brunicardi

379

Burns James H. Holmes and David M. Heimbach

189

8

Wound Healing Adrian Barbul

223

9

Oncology 249 Funda Meric-Bernstam and Raphael E. Pollock

Skin and Subcutaneous Tissue Scott L. Hansen, Stephen J. Mathes, and David M. Young

429

16

The Breast Kirby I. Bland, Samuel W. Beenken, and Edward M. Copeland III

453

17

Disorders of the Head and Neck Richard O. Wein, Rakesh K. Chandra, and Randal S. Weber

501

18

Chest Wall, Lung, Mediastinum, and Pleura 545 Michael A. Maddaus and James D. Luketich

19

Congenital Heart Disease Tara B. Karamlou, Irving Shen, and Ross M. Ungerleider

20

Acquired Heart Disease 645 Aubrey C. Galloway, Ram Sharony, Charles F. Schwartz, Paul C. Saunders, Eugene A. Grossi, and Stephen B. Colvin

21

Thoracic Aortic Aneurysms and Aortic Dissection Joseph S. Coselli and Scott A. LeMaire

vii

611

691

22

Arterial Disease 717 Alan B. Lumsden, Peter H. Lin, Ruth L. Bush, and Changyi Chen

23

Venous and Lymphatic Disease Everett Y. Lam, Mary E. Giswold, and Gregory L. Moneta

295

333

427

15

85

7

Patient Safety, Errors, and Complications in Surgery Mark L. Shapiro and Peter B. Angood

14

61

129

11

Minimally-Invasive Surgery Blair A. Jobe and John G. Hunter

43

Trauma Jon M. Burch, Reginald J. Franciose, and Ernest E. Moore

Transplantation Abhinav Humar and David L. Dunn

361

13

PART II Specific Considerations

3

109

10

Physiologic Monitoring of the Surgical Patient Louis H. Alarcon and Mitchell P. Fink

1

Surgical Infections David L. Dunn and Gregory J. Beilman

6

12

809

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CONTENTS

24

Esophagus and Diaphragmatic Hernia Jeffrey H. Peters and Tom R. DeMeester

835

25

Stomach Daniel T. Dempsey

933

The Surgical Management of Obesity Philip R. Schauer and Bruce D. Schirmer

997

26 27

28

36

Inguinal Hernias 1353 Robert J. Fitzgibbons, Jr., Charles J. Filipi, and Thomas H. Quinn

37

Thyroid, Parathyroid, and Adrenal Geeta Lal and Orlo H. Clark

1395

38

1471

Small Intestine 1017 Edward E. Whang, Stanley W. Ashley, and Michael J. Zinner

Pediatric Surgery David J. Hackam, Kurt Newman, and Henri R. Ford

39

1519

Colon, Rectum, and Anus 1055 Kelli M. Bullard and David A. Rothenberger

Urology Hyung L. Kim and Arie Belldegrun

40

Gynecology Gregory P. Sutton, Robert E. Rogers, William W. Hurd, and Martina F. Mutone

1561

41

Neurosurgery Michael L. Smith and M. Sean Grady

1609

42

Orthopaedics Dempsey Springfield

1653

43

Surgery of the Hand and Wrist Clayton A. Peimer

1721

44

Plastic and Reconstructive Surgery Saleh M. Shenaq, John Y.S. Kim, and Alan Bienstock

1789

29

The Appendix Bernard M. Jaffe and David H. Berger

1119

30

Liver Timothy D. Sielaff and Steven A. Curley

1139

31

Gallbladder and the Extrahepatic Biliary System Margret ´ Oddsdottir ´ and John G. Hunter

32

1187

Pancreas William E. Fisher, Dana K. Andersen, Richard H. Bell, Jr., Ashok K. Saluja, and F. Charles Brunicardi

1221

33

Spleen Adrian E. Park and Rodrick McKinlay

1297

45

34

Abdominal Wall, Omentum, Mesentery, and Retroperitoneum 1317 Robert L. Bell and Neal E. Seymour

Surgical Considerations in the Elderly 1835 Rosemarie E. Hardin and Michael E. Zenilman

46

Anesthesia of the Surgical Patient Robert S. Dorian

35

Soft Tissue Sarcomas 1329 Janice N. Cormier and Raphael E. Pollock

Index

1851

1875

Contributors

Vanita Ahuja, M.D. [CHAPTER 8] Resident Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland

Samuel W. Beenken, M.D., F.R.C.S.(C.), F.A.C.S. [CHAPTER 16] Professor of Surgery University of Alabama at Birmingham Birmingham, Alabama

Louis H. Alarcon, M.D. [CHAPTER 12] Assistant Professor Departments of Surgery and Critical Care Medicine University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

Gregory J. Beilman, M.D., F.A.C.S. [CHAPTER 5] Associate Professor of Surgery and Anesthesia University of Minnesota Medical School Minneapolis, Minnesota

Dana K. Andersen, M.D. [CHAPTER 32] Harry M. Haidek Distinguished Professor and Chairman Department of Surgery University of Massachusetts Memorial Medical School Worcester, Massachusetts

Richard H. Bell, Jr., M.D., F.A.C.S. [CHAPTER 32] Loyal and Edith Davis Professor and Chair Department of Surgery Feinberg School of Medicine Northwestern University Chicago, Illinois

Peter B. Angood, M.D., F.A.C.S., F.C.C.M. [CHAPTER 11] Professor of Surgery Anesthesia and Emergency Medicine Chief, Division of Trauma & Critical Care University of Massachusetts Medical School and UMass-Memorial Health Care System Worcester, Massachusetts

Robert L. Bell, M.D., M.A. [CHAPTER 34] Assistant Professor Department of Surgery Yale University School of Medicine New Haven, Connecticut Arie Belldegrun, M.D., F.A.C.S. [CHAPTER 39] Roy and Carol Doumani Chair in Urologic Oncology Professor of Urology Chief, Division of Urologic Oncology David Geffen School of Medicine at UCLA Los Angeles, California

Chandrakanth Are, M.D. [CHAPTER 8] Clinical Instructor and Assistant Chief of Service Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland

David H. Berger, M.D., F.A.C.S. [CHAPTER 29] Associate Professor and Vice Chair Michael E. DeBakey Department of Surgery Baylor College of Medicine Operative Care Line Executive Chief, Surgical Services Michael E. DeBakey Veterans Affairs Medical Center Houston, Texas

Stanley W. Ashley, M.D. [CHAPTER 27] Professor and Vice Chairman Department of Surgery Brigham and Women’s Hospital/Harvard Medical School Boston, Massachusetts Adrian Barbul, M.D., F.A.C.S. [CHAPTER 8] Surgeon-in-Chief Sinai Hospital of Baltimore Professor and Vice-Chairman Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland

Alan Bienstock, M.D., B.S. [CHAPTER 44] Resident Division of Plastic Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas

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CONTRIBUTORS

Timothy R. Billiar, M.D. [CHAPTER 4] George Vance Foster Professor and Chairman Department of Surgery University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania Kirby I. Bland, M.D., F.A.C.S. [CHAPTER 16] Fay Fletcher Kerner Professor and Chairman Deputy Director, UAB Comprehensive Cancer Center Department of Surgery University of Alabama at Birmingham Birmingham, Alabama F. Charles Brunicardi, M.D., F.A.C.S. [CHAPTERS 14, 32] DeBakey/Bard Professor and Chairman Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Kelli M. Bullard, M.D., F.A.C.S. [CHAPTER 28] Assistant Professor of Surgery and Laboratory Medicine & Pathology University of Minnesota Minneapolis, Minnesota Jon M. Burch, M.D. [CHAPTER 6] Professor of Surgery University of Colorado Health Sciences Center Chief of General and Vascular Surgery Denver Health Medical Center Denver, Colorado Ruth L. Bush, M.D. [CHAPTER 22] Assistant Professor of Surgery Division of Vascular Surgery and Endovascular Therapy Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Steven E. Calvano, Ph.D. [CHAPTER 1] Associate Professor Division of Surgical Sciences Department of Surgery UMDNJ–Robert Wood Johnson Medical School New Brunswick, New Jersey Rakesh K. Chandra, M.D. [CHAPTER 17] Assistant Professor Director, Division of Nasal and Sinus Disorders Residency Program Director Department of Otolaryngology–Head and Neck Surgery University of Tennessee Health Science Center Memphis, Tennessee

Changyi Chen, M.D., Ph.D. [CHAPTER 22] Professor of Surgery Division of Vascular Surgery and Endovascular Therapy Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Orlo H. Clark, M.D. [CHAPTER 37] Professor of Surgery Department of Surgery University of California, San Francisco/Mt. Zion Medical Center San Francisco, California Stephen B. Colvin, M.D. [CHAPTER 20] Chief, Cardiothoracic Surgery New York University School of Medicine New York, New York Edward M. Copeland III, M.D. [CHAPTER 16] Distinguished Professor of Surgery University of Florida College of Medicine Gainesville, Florida Janice N. Cormier, M.D., M.P.H. [CHAPTER 35] Assistant Professor of Surgery Department of Surgical Oncology The University of Texas M.D. Anderson Cancer Center Houston, Texas Joseph S. Coselli, M.D. [CHAPTER 21] Professor and Chief Division of Cardiothoracic Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Steven A. Curley, M.D., F.A.C.S. [CHAPTER 30] Professor, Department of Surgical Oncology Chief, Gastrointestinal Tumor Surgery The University of Texas M.D. Anderson Cancer Center Houston, Texas Tom R. DeMeester, M.D. [CHAPTER 24] The Jeffrey P. Smith Professor of General & Thoracic Surgery Chairman, Department of Surgery Keck School of Medicine University of Southern California Los Angeles, California Daniel T. Dempsey, M.D., F.A.C.S. [CHAPTER 25] Professor and Chairman of Surgery Temple University School of Medicine Philadelphia, Pennsylvania

CONTRIBUTORS

Robert S. Dorian, M.D. [CHAPTER 46] Chairman and Program Director Department of Anesthesiology Saint Barnabas Medical Center Livingston, New Jersey David L. Dunn, M.D., Ph.D. [CHAPTERS 5, 10] Jay Phillips Professor and Chairman Department of Surgery University of Minnesota Medical School Minneapolis, Minnesota David E. Efron, M.D. [CHAPTER 8] Assistant Professor Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Xin-Hua Feng, Ph.D. [CHAPTER 14] Associate Professor of Surgery Division of General Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Charles J. Filipi, M.D., F.A.C.S. [CHAPTER 36] Professor of Surgery Department of Surgery Creighton University Omaha, Nebraska Mitchell P. Fink, M.D. [CHAPTER 12] Professor and Chairman Department of Critical Care Medicine Watson Chair in Surgery University of Pittsburgh Pittsburgh, Pennsylvania William E. Fisher, M.D., F.A.C.S. [CHAPTER 32] Associate Professor of Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Robert J. Fitzgibbons, Jr., M.D. [CHAPTER 36] Harry E. Stuckenhoff Professor of Surgery Department of Surgery Creighton University Omaha, Nebraska Henri R. Ford, M.D. [CHAPTER 38] Benjamin R. Fisher Chair Professor and Chief Division of Pediatric Surgery Children’s Hospital of Pittsburgh University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania

Reginald J. Franciose, M.D. [CHAPTER 6] Assistant Professor of Surgery University of Colorado Health Sciences Center Attending Surgeon Denver Health Medical Center Denver, Colorado Aubrey C. Galloway, M.D. [CHAPTER 20] Professor of Surgery, Cardiothoracic Surgery Director, Cardiac Surgical Research New York University School of Medicine New York, New York Mary E. Giswold, M.D. [CHAPTER 23] Surgical Resident Department of Surgery Oregon Health & Science University Portland, Oregon M. Sean Grady, M.D., F.A.C.S. [CHAPTER 41] Charles Harrison Frazier Professor and Chairman Department of Neurosurgery University of Pennsylvania School of Medicine Philadelphia, Pennsylvania Eugene A. Grossi, M.D. [CHAPTER 20] Professor of Surgery, Cardiothoracic Surgery New York University School of Medicine New York, New York David J. Hackam, M.D., Ph.D. [CHAPTER 38] Assistant Professor of Surgery, Cell Biology and Physiology University of Pittsburgh School of Medicine Attending Pediatric Surgeon Co-Director, Fetal Diagnosis and Treatment Center Children’s Hospital of Pittsburgh Pittsburgh, Pennsylvania Scott L. Hansen, M.D. [CHAPTER 15] Resident, Plastic and Reconstructive Surgery University of California, San Francisco San Francisco, California Brian G. Harbrecht, M.D., F.A.C.S. [CHAPTER 4] Associate Professor of Surgery Department of Surgery University of Pittsburgh Pittsburgh, Pennsylvania Rosemarie E. Hardin, M.D. [CHAPTER 45] Resident Department of Surgery SUNY Health Science Medical Center Brooklyn, New York

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CONTRIBUTORS

David M. Heimbach, M.D., F.A.C.S. [CHAPTER 7] Professor of Surgery University of Washington Burn Center Harborview Medical Center Seattle, Washington

John Y.S. Kim, M.D. [CHAPTER 44] Assistant Professor, Division of Plastic Surgery Department of Surgery Northwestern University School of Medicine Chicago, Illinois

James H. Holmes, M.D. [CHAPTER 7] Burn Fellow & Acting Instructor in Surgery Harborview Medical Center–University of Washington Seattle, Washington

Rosemary A. Kozar, M.D., Ph.D. [CHAPTER 2] Associate Professor of Surgery University of Texas–Houston Houston, Texas

Abhinav Humar, M.D., F.R.C.S. (Can) [CHAPTER 10] Associate Professor Department of Surgery University of Minnesota Minneapolis, Minnesota John G. Hunter, M.D., F.A.C.S. [CHAPTERS 13, 31] Professor and Chairman Department of Surgery Oregon Health & Science University Portland, Oregon William W. Hurd, M.D., F.A.C.O.G., F.A.C.S. [CHAPTER 40] Nicholas J. Thompson Professor and Chair Department of Obstetrics and Gynecology Wright State University School of Medicine Dayton, Ohio Bernard M. Jaffe, M.D. [CHAPTER 29] Professor of Surgery Tulane University School of Medicine New Orleans, Louisiana Blair A. Jobe, M.D. [CHAPTER 13] Assistant Professor Department of Surgery Oregon Health & Science University Portland, Oregon Karen L. Kaplan, M.D. [CHAPTER 3] Professor of Medicine (Hematology/Oncology) University of Rochester School of Medicine and Dentistry Rochester, New York Tara B. Karamlou, M.D. [CHAPTER 19] Senior Research Fellow Division of Cardiothoracic Surgery Oregon Health & Science University Portland, Oregon Hyung L. Kim, M.D. [CHAPTER 39] Assistant Professor Department of Urology Department of Cellular Stress Biology Roswell Park Cancer Institute Buffalo, New York

Geeta Lal, M.D. [CHAPTER 37] Assistant Professor Surgical Oncology and Endocrine Surgery Department of Surgery University of Iowa Hospital and Clinics Iowa City, Iowa Everett Y. Lam, M.D. [CHAPTER 23] Resident Division of Vascular Surgery Oregon Health & Science University Portland, Oregon Scott A. LeMaire, M.D. [CHAPTER 21] Assistant Professor Division of Cardiothoracic Surgery Baylor College of Medicine The Methodist DeBakey Heart Center Houston, Texas Edward Lin, D.O., C.N.S.P. [CHAPTER 1] Assistant Professor of Surgery Division of Gastrointestinal & General Surgery Surgical Metabolism Laboratory Emory University School of Medicine Atlanta, Georgia Peter H. Lin, M.D. [CHAPTER 22] Associate Professor of Surgery Division of Vascular Surgery and Endovascular Therapy Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Xia Lin, Ph.D. [CHAPTER 14] Assistant Professor of Surgery Division of General Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas Stephen F. Lowry, M.D., F.A.C.S. [CHAPTER 1] Professor and Chairman Department of Surgery UMDNJ-Robert Wood Johnson Medical School New Brunswick, New Jersey

CONTRIBUTORS

James D. Luketich, M.D. [CHAPTER 18] Professor and Chief, Division of Thoracic and Foregut Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania

Martina F. Mutone, M.D. [CHAPTER 40] Clinical Assistant Professor Indiana University/Methodist Hospital St. Vincent Hospitals and Health Services Indianapolis, Indiana

Alan B. Lumsden, M.D. [CHAPTER 22] Professor of Surgery Chief of Division of Vascular Surgery and Endovascular Therapy Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas

Kurt Newman, M.D., F.A.C.S. [CHAPTER 38] Executive Director and Surgeon-in-Chief Joseph E. Robert, Jr. Center for Surgical Care Children’s National Medical Center Professor of Surgery and Pediatrics George Washington University School of Medicine Washington, D.C.

Michael A. Maddaus, M.D., F.A.C.S. [CHAPTER 18] Professor and Head, Section of General Thoracic Surgery Garamella-Lynch-Jensen Chair in Thoracic & Cardiovascular Surgery Co-Director, Minimally Invasive Surgery Center University of Minnesota Minneapolis, Minnesota

´ Oddsdottir, ´ Margret M.D. [CHAPTER 31] Professor of Surgery Chief of General Surgery Landspitali–University Hospital Reykjavik, Iceland

Stephen J. Mathes, M.D. [CHAPTER 15] Professor of Surgery Chief, Division of Plastic and Reconstructive Surgery University of California, San Francisco San Francisco, California Jeffrey B. Matthews, M.D., F.A.C.S. [CHAPTER 15] Christian R. Holmes Professor and Chairman Department of Surgery University of Cincinnati Cincinnati, Ohio Rodrick McKinlay, M.D. [CHAPTER 33] Gastrointestinal and Minimally Invasive Surgery Rocky Mountain Associated Physicians Salt Lake City, Utah Funda Meric-Bernstam, M.D., F.A.C.S. [CHAPTER 9] Assistant Professor Department of Surgical Oncology University of Texas M.D. Anderson Cancer Center Houston, Texas Gregory L. Moneta, M.D. [CHAPTER 23] Professor and Chief Vascular Surgery Oregon Health & Science University Portland, Oregon Ernest E. Moore, M.D., F.A.C.S. [CHAPTER 6] Professor and Vice Chairman, Department of Surgery University of Colorado Health Sciences Center Chief of Surgery and Trauma Services Denver Health Medical Center Denver, Colorado Frederick A. Moore, M.D. [CHAPTER 2] James H. “Red” Duke, Jr. Professor & Vice Chairman Department of Surgery The University of Texas Houston Medical School Houston, Texas

xiii

Adrian E. Park, M.D., F.R.C.S.(C), F.A.C.S. [CHAPTER 33] Campbell and Jeanette Plugge Professor of Surgery Professor and Head, Division of General Surgery Department of Surgery University of Maryland Medical Center Baltimore, Maryland Julie E. Park, M.D. [CHAPTER 8] Resident Department of Surgery Johns Hopkins Medical Institutions Baltimore, Maryland Clayton A. Peimer, M.D. [CHAPTER 43] Breech Chair of Orthopaedic Surgery Henry Ford Health System Detroit, Michigan Andrew B. Peitzman, M.D., F.A.C.S. [CHAPTER 4] Professor and Vice-Chairman, Department of Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Jeffrey H. Peters, M.D., F.A.C.S. [CHAPTER 24] Professor and Chairman University of Rochester School of Medicine and Dentistry Surgeon-in-Chief Strong Memorial Hospital Department of Surgery Rochester, New York Raphael E. Pollock, M.D., Ph.D., F.A.C.S. [CHAPTERS 9, 35] Head, Division of Surgery Professor and Chairman Department of Surgical Oncology Senator A.M. Aiken, Jr., Distinguished Chair The University of Texas M.D. Anderson Cancer Center Houston, Texas

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CONTRIBUTORS

Thomas H. Quinn, Ph.D. [CHAPTER 36] Professor of Anatomy and Surgery Director of Clinical Anatomy School of Medicine Creighton University Omaha, Nebraska Robert E. Rogers, M.D. [CHAPTER 40] Emeritus Professor, Obstetrics and Gynecology Indiana University School of Medicine Indianapolis, Indiana David A. Rothenberger, M.D. [CHAPTER 28] Professor of Surgery Chief, Divisions of Colon and Rectal Surgery and Surgical Oncology Department of Surgery University of Minnesota Minneapolis, Minnesota Ashok K. Saluja, Ph.D. [CHAPTER 32] Professor of Surgery, Medicine, and Cell Biology University of Massachusetts Medical School Worcester, Massachusetts Paul C. Saunders, M.D. [CHAPTER 20] Fellow Division of Cardiothoracic Surgery New York University School of Medicine New York, New York Philip R. Schauer, M.D. [CHAPTER 26] Associate Professor of Surgery Director of Bariatric Surgery Chief, Minimally Invasive General Surgery The University of Pittsburgh Pittsburgh, Pennsylvania

Neal E. Seymour, M.D., F.A.C.S. [CHAPTER 34] Associate Professor Tufts University School of Medicine Vice Chairman, Department of Surgery Baystate Medical Center Springfield, Massachusetts Mark L. Shapiro, M.D. [CHAPTER 11] Assistant Professor of Surgery Department of Surgery Division of Trauma and Critical Care University of Massachusetts Medical School Worcester, Massachusetts Ram Sharony, M.D. [CHAPTER 20] Minimally Invasive Cardiac Surgery Fellow Division of Cardiothoracic Surgery New York University Medical Center New York, New York Irving Shen, M.D. [CHAPTER 19] Assistant Professor of Surgery Division of Cardiothoracic Surgery Oregon Health & Science University Portland, Oregon Saleh M. Shenaq, M.D. [CHAPTER 44] Chief, Division of Plastic Surgery Professor of Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, Texas

Bruce D. Schirmer, M.D., F.A.C.S. [CHAPTER 26] Stephen H. Watts Professor of Surgery University of Virginia Health System Charlottesville, Virginia

Timothy D. Sielaff, M.D., Ph.D., F.A.C.S. [CHAPTER 30] Associate Professor Department of Surgery University of Minnesota Minneapolis, Minnesota

Charles F. Schwartz, M.D. [CHAPTER 20] Assistant Professor of Surgery Division of Cardiothoracic Surgery New York University School of Medicine New York, New York

Michael L. Smith, M.D. [CHAPTER 41] Resident Department of Neurosurgery University of Pennsylvania School of Medicine Philadelphia, Pennsylvania

David Schwartz, M.D., Ph.D., F.A.C.C. [CHAPTER 3] Assistant Professor of Medicine Cardiovascular Division Washington University School of Medicine Saint Louis, Missouri

Dempsey Springfield, M.D. [CHAPTER 42] Professor and Chairman Department of Orthopaedics The Mount Sinai School of Medicine New York, New York

Seymour I. Schwartz, M.D., F.A.C.S. [CHAPTER 3] Distinguished Alumni Professor of Surgery University of Rochester School of Medicine and Dentistry Rochester, New York

Gregory P. Sutton, M.D. [CHAPTER 40] Director, Gynecologic Oncology St. Vincent Oncology Center St. Vincent Hospitals and Health Services Indianapolis, Indiana

CONTRIBUTORS

Ross M. Ungerleider, M.D. [CHAPTER 19] Professor of Surgery Chief, Division of Cardiothoracic Surgery Oregon Health & Science University Portland, Oregon Randal S. Weber, M.D., F.A.C.S. [CHAPTER 17] Hubert L. and Olive Stringer, Distinguished Professor and Chairman Department of Head and Neck Surgery University of Texas M.D. Anderson Cancer Center Houston, Texas Richard O. Wein, M.D. [CHAPTER 17] Assistant Professor Department of Otolaryngology and Communicative Sciences University of Mississippi Medical Center Jackson, Mississippi Edward E. Whang, M.D. [CHAPTER 27] Assistant Professor of Surgery Brigham & Women’s Hospital

Harvard Medical School Boston, Massachusetts David M. Young, M.D., F.A.C.S. [CHAPTER 15] Associate Professor of Plastic Surgery Department of Surgery University of California, San Francisco San Francisco, California Michael E. Zenilman, M.D. [CHAPTER 45] Clarence and Mary Dennis Professor and Chairman Department of Surgery SUNY Downstate Medical Center Brooklyn, New York Michael J. Zinner, M.D. [CHAPTER 27] Moseley Professor of Surgery Harvard Medical School Surgeon-in-Chief and Chairman Department of Surgery Brigham & Women’s Hospital Boston, Massachusetts

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Foreword

It began during the summer of 1967 when John DeCarville of McGraw-Hill convened David Hume, Richard Lillehei, G. Tom Shires, Frank Spencer, Edward Storer, and myself and proposed that we edit a new surgical textbook to serve as a companion to Harrison’s Principles of Internal Medicine. We agreed, with the proviso that we could create a textbook that would differ from the previous and existing works in the field of surgery. We envisioned a truly modern textbook of surgery that would be panoramic in its scope by including all surgical specialties, and offer material directed at a sophisticated audience, consisting of medical students, who were regarded as graduate students, and that the text would also incorporate the knowledge sought after by surgeons in training, and as part of the continuing education of practicing surgeons. The narrative’s attraction would be the presentation of the physiologic basis of the practices in addition to the pathology, diagnosis, and therapy, made readable as a consequence of consistency of style. The first edition was published in 1969, and I have had the privilege of shepherding six subsequent editions. In each instance, as part of the credo of modernity, the material was brought up to date by effecting changes of between 30 and 40 percent in the subsequent edition. Now, the time has come to pass the mantle of responsibility to Dr. Brunicardi and his five associate editors, all of whom are actively engaged in clinical practice, research, and education. As Sir William Osler wrote: “Everywhere the old order changes and happy they who can change with it.” The editorship of the past seven editions of Principles of Surgery has generated much personal happiness and satisfaction. I am particularly appreciative of the reception that has been received from the readership. It is my hope that, over our tenure of 35 years, the needs of the audience have been fulfilled, and the current and future editors provide a continuum of the past. Seymour I. Schwartz, M.D., F.A.C.S.

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Preface

For the past 35 years, the Principles of Surgery has been edited by Dr. Seymour Schwartz and a group of outstanding co-editors. It has been considered the leading large textbook for general surgery worldwide. I was surprised and deeply honored to have been asked to assume the role of editor-in-chief and was determined to ensure that the reputation of this legendary book would carry on its tradition of excellence. In this effort, the first assigned task was to select a new group of co-editors. After careful deliberation, five departmental chairmen who are leading scholars in a variety of specialties were selected from universities around the country. Our first meeting to discuss the development of the eighth edition of Schwartz’s Principles of Surgery defined our first goal: to preserve the style and structure of the classic Principles of Surgery with its basic and clinical sections and to preserve the titles of 95% of the chapters. However, it soon became apparent after a thorough review of each chapter that new authors, those who were leaders in their respective fields, would be selected to compose this extensively updated and modernized text. Upon completion, 76% of the chapters are from new authors. These chapters contain the latest in surgical science, surgical techniques, and therapy for students, residents, and surgeons. Six new chapters have been added to round out this eighth edition: Cell, Genomics, and Molecular Surgery, Soft Tissue Sarcomas, Anesthesia of the Surgical Patient, the Surgical Management of Obesity, Patient Safety, Errors, and Complications in Surgery, and Surgical Considerations in the Elderly. Another important component of this work identified by the editorial team was the artwork. A new artist (Philip Ashley & Associates) was selected to direct the art program, which provides clear and consistent learning aids throughout the text and visually reflects the comprehensive and updated nature of this book. The editorial team is deeply honored to carry forward the tradition of this great textbook into the 21st century. As a team we have worked diligently to create a state-of-the-art textbook to help students, residents and surgeons study the craft of surgery and it is to students of surgery of all ages that we dedicate this book. It is your own devotion to learning the language of surgery that will translate into the best care of patients around the world. We hope the textbook will serve as the cornerstone of your own learning program as it has for the study of surgery for the past 35 years. We wish to thank Katie Elsbury and Susie Lee for their exceptional skills in helping edit and coordinate all communication. We wish to thank Marc Strauss, Michelle Watt, and their team at McGraw-Hill for their willingness to work with us. We would also like to thank our families, whose love and support made this book possible. F. Charles Brunicardi, M.D., F.A.C.S. October 2004

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Preface to the First Edition

The raison d’ˆetre for a new textbook in a discipline which has been served by standard works for many years was the Editorial Board’s initial conviction that a distinct need for a modern approach in the dissemination of surgical knowledge existed. As incoming chapters were reviewed, both the need and satisfaction became increasingly apparent and, at the completion, we felt a sense of excitement at having the opportunity to contribute to the education of modern and future students concerned with the care of surgical patients. The recent explosion of factual knowledge has emphasized the need for a presentation which would provide the student an opportunity to assimilate pertinent facts in a logical fashion. This would then permit correlation, synthesis of concepts, and eventual extrapolation to specific situations. The physiologic bases for diseases are therefore emphasized and the manifestations and diagnostic studies are considered as a reflection of pathophysiology. Therapy then becomes logical in this schema and the necessity to regurgitate facts is minimized. In appreciation of the impact which Harrison’s Principles of Internal Medicine has had, the clinical manifestations of the disease processes are considered in detail for each area. Since the operative procedure represents the one element in the therapeutic armamentarium unique to the surgeon, the indications, important technical considerations, and complications receive appropriate emphasis. While we appreciate that a textbook cannot hope to incorporate an atlas of surgical procedures, we have provided the student a single book which will satisfy the sequential demands in the care and considerations of surgical patients. The ultimate goal of the Editorial Board has been to collate a book which is deserving of the adjective “modern.” We have therefore selected as authors dynamic and active contributors to their particular fields. The au courant concept is hopefully apparent throughout the entire work and is exemplified by appropriate emphasis on diseases of modern surgical interest, such as trauma, transplantation, and the recently appreciated importance of rehabilitation. Cardiovascular surgery is presented in keeping with the exponential strides recently achieved. There are two major subdivisions to the next. In the first twelve chapters, subjects that transcend several organ systems are presented. The second portion of the book represents a consideration of specific organ systems and surgical specialties. Throughout the text, the authors have addressed themselves to a sophisticated audience, regarding the medical student as a graduate student, incorporating material generally sought after by the surgeon in training and presenting information appropriate for the continuing education of the practicing surgeon. The need for a text such as we have envisioned is great and the goal admittedly high. It is our hope that this effort fulfills the expressed demands. Seymour I. Schwartz, M.D., F.A.C.S.

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Schwartz’s Principles of

Surgery

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PART I

BASIC CONSIDERATIONS

1

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CHAPTER

1

Systemic Response to Injury and Metabolic Support Edward Lin, Steven E. Calvano, and Stephen F. Lowry

Introduction

Cellular Response to Injury

The Systemic Inflammatory Response Syndrome (SIRS)

Gene Expression and Regulation Cell Signaling Pathways Heat Shock Proteins G-Protein Receptors Ligand-Gated Ion Channels Receptor Tyrosine Kinases Janus Kinase/Signal Transduction and Activator of Transcription (STAT) Signaling Suppressors of Cytokine Signaling Mitogen-Activated Protein Kinases Nuclear Factor-κB Toll-Like Receptors and CD14 Tumor Necrosis Factor and CD95-Induced Apoptosis Cell-Mediated Inflammatory Response Platelets Lymphocytes and T-Cell Immunity Eosinophils Mast Cells Monocytes Neutrophils

Central Nervous System Regulation of Inflammation Reflex Inhibition of Inflammation Afferent Signals to the Brain Cholinergic Anti-Inflammatory Pathways Hormonal Response to Injury Hormone Signaling Pathways Adrenocorticotropic Hormone Cortisol and Glucocorticoids Macrophage Inhibitory Factor Growth Hormones and Insulin-Like Growth Factors Catecholamines Aldosterone Insulin Acute Phase Proteins Mediators of Inflammation Cytokines Heat Shock Proteins Reactive Oxygen Metabolites Eicosanoids Fatty Acid Metabolites Kallikrein-Kinin System Serotonin Histamine

Endothelium-Mediated Injury Neutrophil-Endothelium Interaction Nitric Oxide Prostacyclin Endothelins Platelet-Activating Factor Atrial Natriuretic Peptides

Cytokine Response to Injury

Surgical Metabolism

Tumor Necrosis Factor Interleukin-1 Interleukin-2 Interleukin-4 Interleukin-6 Interleukin-8 Interleukin-10 Interleukin-12 Interleukin-13 Interleukin-15 Interleukin-18 Interferon-γ Granulocyte-Macrophage Colony-Stimulating Factor High Mobility Group Box-1

Metabolism During Fasting Metabolism Following Injury Lipid Metabolism Following Injury Carbohydrate Metabolism Protein and Amino Acid Metabolism Nutrition in the Surgical Patient Estimating Energy Requirements Vitamins and Minerals Overfeeding Enteral Nutrition Rationale for Enteral Nutrition Enteral Formulas Access for Enteral Nutritional Support

3

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SCHWARTZ’S PRINCIPLES OF SURGERY/BASIC CONSIDERATIONS

Parenteral Nutrition Rationale for Parenteral Nutrition Total Parenteral Nutrition Peripheral Parenteral Nutrition Initiating Parenteral Nutrition Intravenous Access Methods Complications of Parenteral Nutrition Technical Complications Metabolic Complications Intestinal Atrophy Special Formulations Glutamine and Arginine Omega-3 Fatty Acids Nucleotides

INTRODUCTION The inflammatory response to injury and activation of cellular processes are inherently designed to restore tissue function and eradicate invading microorganisms. Local injuries of limited duration are usually followed by functional restoration with minimal intervention. By contrast, major insults to the host are associated with an overwhelming inflammatory response that, without appropriate and timely intervention, can lead to multiple organ failure and adversely impact patient survival. Therefore understanding how the inflammatory response is mobilized and ultimately controlled provides a functional framework upon which interventions and therapeutics are formulated for the surgical patient. The maturation of minimally invasive techniques for major surgery during the last decade has brought complementary perspectives to the injury response paradigm, and the immunologic benefits for these surgical approaches are undergoing validation. Furthermore, the sequencing of the human genome and available technology such as deoxyribonucleic acid (DNA) microarray analysis potentially affords surgeons additional tools to profile the genetic mechanisms governing the host response to injury. This chapter addresses the hormonal, immunologic, and cellular responses to injury. The resultant metabolic and nutritional alterations of injury are discussed in continuum because the utilization of fuel substrates during injury also is subject to the influences of hormonal and inflammatory mediators.

THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) Conceptually, the systemic response to injury can be broadly compartmentalized into two phases: (1) a proinflammatory phase characterized by activation of cellular processes designed to restore tissue function and eradicate invading microorganisms, and (2) an anti-inflammatory or counterregulatory phase that is important for preventing excessive proinflammatory activities as well as restoring homeostasis in the individual (Fig. 1-1). While the terminologies that describe the various facets of systemic inflammation are often used interchangeably, there are distinct criteria for each term (Table 1-1).

SIRS

Recovery

MOF

CARS

HOURS

The central nervous system, operating through autonomic signaling, has an integral role in regulating the inflammatory response that is

DAYS

FIG. 1-1. Schematic representation of the systemic inflammatory response syndrome (SIRS) to injury, followed by a period of convalescence mediated by the counterregulatory anti-inflammatory response syndrome (CARS). Severe inflammation may lead to acute multiple organ failure (MOF) and early death following injury (gray solid arrow). A lesser inflammatory response followed by excessive CARS may induce a prolonged immunosuppressed state that can also be deleterious to the host (broken arrow). Normal recovery after injury requires a period of systemic inflammation followed by a return to homeostasis (black solid arrow). (Concept adapted with permission from Guirao X, Lowry SF: Biologic control of injury and inflammation: Much more than too little or too late. World J Surg 20:437, 1996.)

primarily involuntary. Classically, the autonomic system regulates heart rate, blood pressure, respiratory rate, gastrointestinal motility, and body temperature. An additional role of the autonomic nervous system is to regulate inflammation in a reflex manner, much like the patellar tendon reflex. Inflammation originating from a specific location sends afferent signals to the hypothalamus, which in turn rapidly relays opposing anti-inflammatory messages to the site of inflammation to reduce inflammatory mediator release by immunocytes (Fig. 1-2).

Afferent Signals to the Brain The central nervous system (CNS) receives immunologic input from both the circulation and neural pathways. Indeed, areas of the CNS devoid of blood-brain barrier admit the passage of inflammatory mediators such as tumor necrosis factor (TNF-α). Fevers, anorexia, and depression in illness are attributed to the humoral (circulatory) route of inflammatory signaling. While the mechanism for vagal Table 1-1 Clinical Spectrum of Infection and Systemic Inflammatory Response Syndrome (SIRS) Term

Definition

Infection SIRS

Identifiable source of microbial insult Two or more of following criteria Temperature ≥38◦ C or ≤36◦ C Heart rate ≥90 beats/min Respiratory rate ≥20 breaths/min or Paco2 ≤32 mm Hg or mechanical ventilation White blood cell count ≥12,000/µL or ≤4000/µL or ≥10% band forms Identifiable source of infection + SIRS Sepsis + organ dysfunction Sepsis + cardiovascular collapse (requiring vasopressor support)

CENTRAL NERVOUS SYSTEM REGULATION OF INFLAMMATION Reflex Inhibition of Inflammation

MOF

Sepsis Severe sepsis Septic shock

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5

Central Nervous System

ACTH Glucocorticoids INJURY INFLAMMATION FIG. 1-2. Neural circuit relaying messages of localized injury to the brain (nucleus tractus solitarius). The brain follows with a hormonal response (ACTH, glucocorticoids) into the systemic circulation and by sympathetic release. The vagal response rapidly induces acetylcholine release directed at the site of injury to curtail the inflammatory response elicited by the activated immunocytes. This vagal response occurs in real time and is site specific. (Concept adapted and recreated with permission from Tracey KJ: The inflammatory reflex. Nature 420:853, 2002.)

Injury Site

Sensory Vagus

Sympathetic TNF IL-1

EPI, NOREPI

INFLAMMATORY CASCADE

sensory input is not fully understood, it has been demonstrated that afferent stimuli to the vagus nerve include cytokines (e.g., TNF-α and interleukin [IL]-1), baroreceptors, chemoreceptors, and thermoreceptors originating from the site of injury. This phenomenon is further demonstrated by blunting of fever response in animals after regional vagotomy at the site of injury.

Cholinergic Anti-Inflammatory Pathways Tracey and colleagues have further linked reflex inhibition of inflammation to the parasympathetic signaling pathway whereby acetylcholine, the primary neurotransmitter of the parasympathetic system, reduces tissue macrophage activation. Furthermore, cholinergic stimulation directly reduces tissue macrophage release of the proinflammatory mediators TNF-α, IL-1, IL-18, and high mobility group protein (HMG-1), but not the anti-inflammatory cytokine IL-10. The attenuated inflammatory response induced by cholinergic stimuli was further validated by the identification of acetylcholine (nicotinic) receptors on tissue macrophages. In experimental models, direct electrical stimulation of the vagus nerve inhibits the tissue synthesis of inflammatory cytokines in the liver, spleen, and heart and reduces circulating levels as well. Complete vagotomy in mice significantly increases proinflammatory mediator release in response to injury. In summary, vagal stimulation reduces heart rate, increases gut motility, dilates arterioles, and causes pupil constriction, as well as regulates inflammation. Unlike the humoral anti-inflammatory mediators that are released into the circulation and allowed to travel to a site of injury, signals discharged from the vagus nerve are precisely targeted at the site of injury or infection. Moreover, this cholinergic signaling occurs rapidly in real time. From the available preclinical studies, it can be proposed that impaired cholinergic activity from the vagus nerve portends a greater proinflammatory response in patients who are critically ill.

Parasympathetic (Motor Vagus)

Acetylcholine

HORMONAL RESPONSE TO INJURY Hormone Signaling Pathways Hormones are chemically classified as polypeptides (e.g., cytokines, glucagon, and insulin), amino acids (e.g., epinephrine, serotonin, and histamine), or fatty acids (e.g., glucocorticoids, prostaglandins, and leukotrienes). Most hormone receptors generate signals by one of three major pathways, which overlap. Specifically, these receptor pathways are (1) receptor kinases such as insulin and insulinlike growth factor receptors, (2) guanine nucleotide-binding or G-protein receptors such as neurotransmitter and prostaglandin receptors, and (3) ligand-gated ion channels which permit ion transport when activated. Upon activation of membrane receptors, secondary signaling pathways are often utilized to amplify the initial stimuli. Hormone signals are further mediated by intracellular receptors with binding affinities for both the hormone itself, as well as for the targeted gene sequence on the DNA. These intracellular receptors may be located within the cytosol or may already be localized in the nucleus, bound to the DNA. The classic example of a cytosolic hormonal receptor is the glucocorticoid (GC) receptor (Fig. 1-3). Intracellular GC receptors are maintained in the cytosol by linking to the stress-induced protein, heat shock protein (HSP). When the glucocorticoid ligand binds to the GC receptor, the dissociation of HSP from the receptor activates the receptor-ligand complex and is transported to the nucleus. Virtually every hormone of the hypothalamic-pituitary-adrenal (HPA) axis influences the physiologic response to injury and stress (Table 1-2), but some with direct influence on the inflammatory response or immediate clinical impact will be highlighted.

Adrenocorticotropic Hormone Adrenocorticotropic hormone (ACTH) is synthesized and released by the anterior pituitary. In healthy humans, ACTH release

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SCHWARTZ’S PRINCIPLES OF SURGERY/BASIC CONSIDERATIONS

DNA S

HSP

HSP

mRNA

S

S

S

R

S

R

S

R

S

S

Cytoplasmic Membrane

is regulated by circadian signals such that the greatest elevation of ACTH occurs late at night until the hours immediately before sunrise. This pattern is dramatically altered or obliterated in the injured subject. Most injury is characterized by elevations in corticotropinreleasing hormone and ACTH that are proportional to the severity of injury. Pain, anxiety, vasopressin, angiotensin II, cholecystokinin, vasoactive intestinal polypeptide (VIP), catecholamines, and proinflammatory cytokines are all prominent mediators of ACTH release in the injured patient. Table 1-2 Hormones Regulated by the Hypothalamus, Pituitary, and Autonomic System Hypothalamic Regulation Corticotropin-releasing hormone Thyrotropin-releasing hormone Growth hormone-releasing hormone Luteinizing hormone-releasing hormone Anterior Pituitary Regulation Adrenocorticotropic hormone Cortisol Thyroid-stimulating hormone Thyroxine Triiodothyronine Growth hormone Gonadotrophins Sex hormones Insulin-like growth factor Somatostatin Prolactin Endorphins Posterior Pituitary Regulation Vasopressin Oxytocin Autonomic System Norepinephrine Epinephrine Aldosterone Renin-angiotensin system Insulin Glucagon Enkephalins

Nucleus

Protein Synthesis

FIG. 1-3. Simplified schematic of steroid transport into the nucleus. Steroid molecules (S) diffuse readily across cytoplasmic membranes. Intracellularly the receptors (R) are rendered inactive by being coupled to heat shock protein (HSP). When S and R bind, HSP dissociates, and the S-R complex enters the nucleus where the S-R complex induces DNA transcription, resulting in protein synthesis.

Within the zona fasciculata of the adrenal gland, ACTH signaling activates intracellular pathways that lead to glucocorticoid production (Fig. 1-4). Conditions of excess ACTH stimulation will result in adrenal cortical hypertrophy.

Cortisol and Glucocorticoids Cortisol is the major glucocorticoid in humans and is essential for survival during significant physiologic stress. Following injury, cortisol is elevated depending on the type of systemic stress. Burn patients have elevated circulating cortisol levels for up to 4 weeks, while soft tissue injury and hemorrhage may exhibit shorter periods of cortisol elevation. Metabolically, cortisol potentiates the actions of glucagon and epinephrine that manifest as hyperglycemia. In the liver, cortisol stimulates the enzymatic activities favoring gluconeogenesis, but induces insulin resistance in muscles and adipose tissue. In skeletal muscle, cortisol induces protein degradation as well as the release of lactate that serve as substrates for hepatic gluconeogenesis. During injury, cortisol potentiates the release of free fatty acids, triglycerides, and glycerol from adipose tissue as a means of providing additional energy sources. Acute adrenal insufficiency (AAI) can be a life-threatening complication most commonly seen in acutely ill patients with adrenal suppression from exogenously administered glucocorticoids with consequent atrophy of the adrenal glands. Clinically, these patients present with weakness, nausea, vomiting, fever, and hypotension. Objective findings include hypoglycemia from decreased gluconeogenesis, hyponatremia from impaired renal tubular sodium resorption, and hyperkalemia from diminished kaliuresis. In addition to cortisol deficiency, insufficient mineralocorticoid (aldosterone) activity also contributes to hyponatremia and hyperkalemia. Glucocorticoids have long been employed as effective immunosuppressive agents. Immunologic changes associated with glucocorticoid administration include thymic involution, depressed cellmediated immune responses reflected by decreases in T-killer and natural killer cell functions, T-lymphocyte blastogenesis, mixed lymphocyte responsiveness, graft-versus-host reactions, and delayed hypersensitivity responses. With glucocorticoid administration, monocytes lose the capacity for intracellular killing but appear

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7

Cholesterol ACTH Pregnenolone

Progesterone

17-α-OH-Pregnenolone Dehydroepiandrosterone

FIG. 1-4. Steroid synthesis from cholesterol. Adrenocorticotropic hormone (ACTH) is a principal regulator of steroid synthesis. The end products are mineralocorticoids, glucocorticoids, and sex steroids.

11-Deoxycorticosterone

17-α-OH-progesterone

Corticosterone

11-Deoxycortisol

Androstenedione Testosterone

Aldosterone

Cortisol

Estradiol

MINERALOCORTICOID

GLUCOCORTICOID

SEX STEROIDS

to maintain normal chemotactic and phagocytic properties. For neutrophils, glucocorticoids inhibit intracellular superoxide reactivity, suppress chemotaxis, and normalize apoptosis signaling mechanisms. However, neutrophil phagocytosis function remains unchanged. Finally, glucocorticoid infusion in human endotoxemia downregulates proinflammatory cytokine production (TNF-α, IL1, and IL-6) and increases the production of the anti-inflammatory mediator IL-10. This glucocorticoid-induced downregulation of cytokine stimulation serves an important negative regulatory function in the inflammatory response. Clinically, the administration of pharmacologic doses of glucocorticoids has been associated with modest reductions in proinflammatory response in septic shock, surgical trauma, and coronary artery bypass surgery. However, the appropriate dosing, timing, and duration of glucocorticoid administration have not been validated.

Macrophage Inhibitory Factor Macrophage inhibitory factor (MIF) is a glucocorticoid antagonist produced by the anterior pituitary that potentially reverses the immunosuppressive effects of glucocorticoids. MIF can be secreted systemically from the anterior pituitary and by T lymphocytes situated at the sites of inflammation. MIF is a proinflammatory mediator that potentiates gram-negative and gram-positive septic shock. In mice endotoxemia experiments, the administration of anti-MIF significantly improves survival.

Growth Hormones and Insulin-Like Growth Factors During periods of stress, growth hormone (GH) promotes protein synthesis and also enhances the mobilization of fat stores. The protein synthesis properties of growth hormone in the recovering patient are mediated in part by the secondary release of insulinlike growth factor-1 (IGF-1). IGF, formerly called somatomedin C, circulates predominantly in bound form with several binding proteins and promotes amino acid incorporation and cellular proliferation and attenuates proteolysis. In the liver, IGFs are mediators of protein synthesis and glycogenesis. In adipose tissue, IGF increases glucose uptake and fat utilization. In skeletal muscles, IGF increases glucose uptake and protein synthesis. IGF also has a role in skeletal growth by promoting the incorporation of sulfate and proteoglycans into cartilage. The effects of IGF-1 can be inhibited

by interleukin (IL)-1α, TNF-α, and IL-6. The decrease in protein synthesis and observed negative nitrogen balance following injury is attributed in large part to a reduction in IGF-1 levels. GH administration has been shown to improve the clinical course of pediatric burn patients. Its use in injured adult patients remains unproven. The liver is the predominant source of IGF-1, and pre-existing hepatic dysfunction (e.g., end-stage liver disease and protein-energy malnutrition) may further contribute to the negative nitrogen balance following injury. IGF binding proteins also are produced within the liver and are necessary for effective transport of IGF to the cell. IGF has the potential for attenuating the catabolic effects following surgical insults. Growth hormones also stimulate leukocyte function and cell proliferation, but the clinical benefits of such a response are unclear.

Catecholamines The hypermetabolic state observed following severe injury is attributed to activation of the adrenergic system. Both norepinephrine (NE) and epinephrine (EPI) are increased three- to fourfold in plasma immediately following injury, with elevations lasting 24 to 48 hours before returning toward baseline levels. In the liver, EPI promotes glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis. It also causes decreased insulin release, but increases glucagon secretion. Peripherally, EPI increases lipolysis in adipose tissues and induces insulin resistance in skeletal muscle. These collectively manifest as stress-induced hyperglycemia, not unlike the effects of cortisol on blood sugar. Catecholamines also increase the secretion of thyroid and parathyroid hormones, T4 , T3 , and renin, but inhibit the release of aldosterone. Like cortisol, EPI enhances leukocyte demargination with resultant neutrophilia and lymphocytosis. However, EPI occupation of β receptors present on leukocytes increases intracellular cyclic adenosine monophosphate (cAMP) and ultimately decreases lymphocyte responsiveness to mitogens. There is strong evidence that blockade of β receptors in children with thermal injury reduces cardiac oxygen consumption and retention of lean muscle mass. In noncardiac surgical patients with heart disease, perioperative β-receptor blockade also reduced sympathetic activation and cardiac oxygen demand with significant reductions in cardiac-related deaths.

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Table 1-3 Cytokines and Their Sources Cytokine

Source

Comment

TNF-α

Macrophages/monocytes Kupffer cells Neutrophils NK cells Astrocytes Endothelial cells T lymphocytes Adrenal cortical cells Adipocytes Keratinocytes Osteoblasts Mast cells Dendritic cells Macrophages/monocytes B and T lymphocytes NK cells Endothelial cells Epithelial cells Keratinocytes Fibroblasts Osteoblasts Dendritic cells Astrocytes Adrenal cortical cells Megakaryocytes Platelets Neutrophils Neuronal cells T lymphocytes

Among earliest responders following injury; half-life 20

Relative Risk 1.0 15.8–16.3

5.9–19.5 2.0–6.1 1.9–3.7

source: Adapted from Samet JM: Health benefits of smoking cessation. Clin Chest Med 12:673, 1991.

FIG. 18-14. Age-adjusted cancer-related mortality rates in men. (Adapted with permission from U.S. Mortality Public Use Data Tapes, 1960 to 1999; U.S. Mortality Volumes 1930 to 1959; National Center for Health Statistics; and Centers for Disease Control and Prevention.)

secondary scar formation also leads to a higher risk of primary lung carcinoma. Over 3000 chemicals have been identified in tobacco smoke, but the main chemical carcinogens are polycyclic aromatic hydrocarbons. Once inhaled and absorbed, these compounds become mutagenic through their activation by specific enzymes, binding to macromolecules such as deoxyribonucleic acid (DNA), and then induction of mutations. In treating any patient with a previous smoking history, it is important to remember that field cancerization of the entire aerodigestive tract has likely occurred. The patient’s risk is increased for cancers of the oral cavity, pharynx, larynx, tracheobronchial tree and lung, and esophagus. In examining such patients, a detailed history and physical examination of these organ systems must be performed.

Normal Lung Histology The lung can be conveniently viewed as two linked components: the tracheobronchial tree (or conducting airways component) and the alveolar spaces (or gas exchange component). The tracheobronchial tree consists of approximately 23 airway divisions to the level of the alveoli. It includes the main bronchi, lobar bronchi, segmental bronchi (to designated bronchopulmonary segments), and terminal bronchioles (i.e., the smallest airway vessels that lack alveoli and are lined by bronchial epithelium). The tracheobronchial tree is normally lined by pseudostratified ciliated columnar cells and mucous (or goblet) cells, which both derive from basal cells (Fig. 18-15). Ciliated cells predominate. Goblet cells, which release mucus, can significantly increase in number in acute bronchial injury, such as exposure to cigarette smoke. The normal bronchial epithelium also contains bronchial submucosal glands, which are mixed salivary-type glands containing mucous cells, serous cells, and Kulchitsky cells. Kulchitsky cells are neuroendocrine cells; they are also found within the surface epithelium (see Fig. 18-15). The bronchial submucosal glands can give rise to salivary gland–type tumors (previously referred to as “bronchial gland tumors”), including mucoepidermoid carcinomas and adenoid cystic carcinomas.

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559

A

FIG. 18-15. Normal lung histology. A . Pseudostratified ciliated columnar cells and mucous cells normally line the tracheobronchial tree. B . A Kulchitsky cell is depicted (arrow).

B

The alveolar spaces or alveoli have two primary cell types, referred to as type I and II pneumocytes. Type I pneumocytes cover 95% of the surface area of the alveolar wall, but comprise only 40% of the total number of alveolar epithelial cells. These cells are not capable of regeneration because they have no mitotic potential. Type II pneumocytes cover only 3% of the alveolar surface, but comprise 60% of the alveolar epithelial cells. In addition, clusters of neuroendocrine cells are seen in the alveolar spaces.

Preinvasive Lesions As with epithelial tumors of other organs, precancerous changes can be seen in the respiratory tract. Three precancerous lesions are currently recognized: squamous dysplasia and carcinoma in situ, atypical adenomatous hyperplasia (AAH), and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). The term “precancerous” does not mean that an inevitable progression to

invasive carcinoma will occur, but such lesions do constitute a clear marker of the potential for later development of invasive cancer.

Squamous Dysplasia and Carcinoma In Situ. Cigarette smoke can induce a metaplastic change of the tracheobronchial pseudostratified epithelium to squamous mucosa, which is a normal response to injury. With the development of cellular abnormalities in the metaplastic squamous mucosa, squamous dysplasia evolves. It involves increased cell size, an increased number of cell layers, an increased nuclear:cytoplasmic ratio, increased mitoses, and changes in cellular polarity. Gradations are considered mild, moderate, or severe. Carcinoma in situ represents carcinoma still confined by the basement membrane. Once the in situ tumor invades beyond the basement membrane, invasive squamous cell carcinoma is present. Atypical Adenomatous Hyperplasia. AAH is defined as a lesion smaller than 5.0 mm, comprising epithelial cells lining the

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

alveoli that are similar to type II pneumocytes. Histologically, AAH is similar to bronchoalveolar carcinoma. It represents the beginning stage of a stepwise evolution to bronchoalveolar carcinoma and then to adenocarcinoma.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia. This rare lesion represents a diffuse proliferation of neuroendocrine cells, but without invasion of the basement membrane. It can exist as a diffuse increase in the number of single neuroendocrine cells, or as small lesions less than 5.0 mm in diameter. Lesions that breach the basement membrane or that are over 5.0 mm in size are carcinoid tumors.

Invasive or Malignant Lesions The term bronchial carcinoma is synonymous with lung cancer in general. Both terms refer to any epithelial carcinoma occurring in the bronchopulmonary tree. Currently, the pathologic diagnosis of the various types of lung cancer is based on light microscopic criteria. Immunohistochemical staining and electron microscopy are also used as adjuncts in diagnosis, particularly in the assessment of potential neuroendocrine tumors. Lung cancer is broadly divided into two main groups based primarily on light microscopic observations: non-small-cell lung carcinoma and neuroendocrine tumors (typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma, and small-cell carcinoma).

Non-Small-Cell Lung Carcinoma. The term non-smallcell lung carcinoma (NSCLC) is used to distinguish a group of tumors from small-cell carcinoma. Tumors in the NSCLC group include squamous cell carcinoma, adenocarcinoma (including bronchoalveolar carcinoma), and large-cell carcinoma. Although they differ in appearance histologically, their clinical behavior and treatment is similar. As such, they are usefully thought of as a uniform group. However, each type has unique features that affect their clinical presentation and findings. Squamous Cell Carcinoma. Squamous cell carcinoma accounts for 30 to 40% of lung cancers. It is the cancer most frequently found in men and is highly correlated with cigarette smoking. Histologically, cells develop a pattern of clusters with intracellular bridges and keratin pearls. Importantly, squamous cell carcinoma is primarily located centrally and arises in the major bronchi, often causing the typical symptoms of centrally-located tumors, such as hemoptysis, bronchial obstruction with atelectasis, dyspnea, and pneumonia. Occasionally a more peripherally-based squamous cell carcinoma will develop in a tuberculosis scar or in the wall of a bronchiectatic cavity. Central necrosis is frequent and may lead to the radiographic findings of a cavity (possibly with an air-fluid level). Such cavities may become infected, with resultant abscess formation. Adenocarcinoma. The incidence of adenocarcinoma has increased over the last several decades, and it now accounts for 25 to 40% of all lung cancers. It occurs with equal frequency in males and females. In contradistinction to squamous cell carcinoma, adenocarcinoma is most often a peripherally-based tumor, thus it is frequently discovered incidentally on routine chest radiographs. Symptoms of chest wall invasion or malignant pleural effusions dominate. Histologically, adenocarcinoma is composed of glands with or without mucin production, combined with destruction of contiguous lung architecture. Bronchoalveolar Carcinoma. Bronchoalveolar carcinoma (BAC) is a relatively unusual (5% of all lung cancers) subtype of adenocarcinoma that has a unique growth pattern that differs from adenocarcinoma. Rather than invading and destroying contiguous

lung parenchyma, tumor cells multiply and fill the alveolar spaces. To be classified as a pure BAC, no evidence of destruction of surrounding lung parenchyma should be seen. When destruction is seen with areas of classic BAC, the tumor is instead classified as an adenocarcinoma with BAC features. Because of their growth within alveoli, BAC tumor cells from one site can aerogenously seed other parts of the same lobe or lung, or the contralateral lung. This growth pattern and tendency to seed can produce three radiographic presentations: a single nodule, multiple nodules (in single or multiple lobes), or a diffuse form with an appearance mimicking that of a lobar pneumonia. Because tumor cells fill the alveolar spaces and envelop small airways rather than destroying them, air bronchograms can be seen, unlike with other carcinomas. Large-Cell Carcinoma. Large-cell carcinoma accounts for 10 to 20% of lung cancers and may be located centrally or peripherally. As implied by the name, the cells are large, with diameters of 30 to 50 µm. They are often admixed with other cell types such as squamous cells or adenocarcinoma. Large-cell carcinoma can be confused with a large-cell variant of neuroendocrine carcinoma, with immunohistochemical staining usually allowing diagnostic distinction between the two.

Neuroendocrine Neoplasms. Neuroendocrine tumors of the lung have been plagued by a confusing array of differing classifications. Over the last decade, progress in understanding and classifying these tumors has been made based on detailed immunohistochemical and electron microscopic studies. In particular, immunohistochemical staining for neuroendocrine markers (including chromogranins, synaptophysin, CD57, and neuronspecific enolase) is essential to accurately diagnose most tumors. Recently, neuroendocrine lung tumors have been reclassified into neuroendocrine hyperplasia and three separate grades of neuroendocrine carcinoma (NEC). Listed below is the grading system now applied to NEC (left column), with the previously used common name (right column): Grade I NEC Grade II NEC Grade III NEC

Classic or typical carcinoid Atypical carcinoid Large-cell type Small-cell type

Grade I NEC (classic or typical carcinoid) is a low-grade NEC. An epithelial tumor, it arises primarily in the central airways, although 20% of the time it occurs peripherally. It occurs primarily in younger patients. Because of the central location, it classically presents with hemoptysis, with or without airway obstruction and pneumonia. Histologically, tumor cells are arranged in cords and clusters with a rich vascular stroma. This vascularity can lead to life-threatening hemorrhage with even simple bronchoscopic biopsy maneuvers. Regional lymph node metastases are seen in 15% of patients, but rarely spread systemically or cause death. Grade II NEC (atypical carcinoid) describes a group of tumors with a degree of aggressive clinical behavior. Unlike Grade I NEC, these tumors are etiologically linked to cigarette smoking and are more likely to be peripherally located. Histologic findings may include areas of necrosis, nuclear pleomorphism, and higher mitotic rates. These tumors have a much higher malignant potential. Lymph node metastases are found in 30 to 50 percent of patients. At the time of their diagnosis, 25 percent of patients already have remote metastases. Grade III NEC large-cell type tumors occur primarily in heavy smokers. These tumors tend to occur in the middle to peripheral

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lung fields. They are often large with central necrosis and a high mitotic rate. Their neuroendocrine nature is revealed by positive immunohistochemical staining for at least one neuroendocrine marker. Grade III NEC small-cell type (small-cell lung carcinoma [SCLC]) is the most malignant NEC, and accounts for 25% of all lung cancers. These tumors are centrally located and consist of smaller cells with a diameter of 10 to 20 µm that have little cytoplasm and very dark nuclei. They also have a high mitotic rate and areas of extensive necrosis. Multiple mitoses are easily seen. Importantly, very small bronchoscopic biopsies can distinguish NSCLC from SCLC, but crush artifact may make NSCLC appear similar to SCLC. If uncertainty exists, special immunohistochemical stains or rebiopsy (or both) will be necessary. These tumors are the leading producer of paraneoplastic syndromes.

Salivary Gland–Type Neoplasms. The tracheobronchial tree has salivary-type submucosal bronchial glands interspersed throughout. These glands can give rise to tumors that are histologically identical to those seen in the salivary glands. The two most common are adenoid cystic carcinoma and mucoepidermoid carcinoma. Both tumors occur centrally due to their site of origin. Adenoid cystic carcinoma is a slow-growing tumor that is locally and systemically invasive. It tends to grow submucosally and infiltrate along perineural sheaths. Mucoepidermoid carcinoma consists of squamous and mucous cells and is graded as low or high grade, depending on the mitotic rate and degree of necrosis. Clinical Presentation Lung cancer displays one of the most diverse presentation patterns of all human maladies (Table 18-2). The wide variety of symptoms and signs is related to (1) histologic features, which often help determine the anatomic site of origin in the lung; (2) the specific tumor location in the lung and its relationship to surrounding structures; (3) biologic features, and the production of a variety of paraneoplastic syndromes; and (4) the presence or absence of metastatic disease.

Tumor Histology Squamous cell and small-cell carcinomas frequently arise in main, lobar, or first segmental bronchi, which are collectively referred to as the central airways. Symptoms of airway irritation or obstruction are common, and include cough, hemoptysis,

wheezing (due to high-grade airway obstruction), dyspnea (due to bronchial obstruction with or without postobstructive atelectasis), and pneumonia (caused by airway obstruction with secretion retention and atelectasis). In contrast, adenocarcinomas are often located peripherally. For this reason, they are often discovered incidentally as an asymptomatic peripheral lesion on chest x-ray. When symptoms occur, they are due to pleural or chest wall invasion (pleuritic or chest wall pain) or pleural seeding with malignant pleural effusion. Bronchoalveolar carcinoma (a variant of adenocarcinoma) may present as a solitary nodule, as multifocal nodules, or as a diffuse infiltrate mimicking an infectious pneumonia (pneumonic form). In the pneumonic form, severe dyspnea and hypoxia may occur, sometimes with expectoration of large volumes (over 1 L/d) of lighttan colored fluid, with resultant dehydration and electrolyte imbalance. Because bronchoalveolar carcinoma tends to fill the alveolar spaces as it grows (as opposed to the typical invasion, destruction, and compression of lung architecture seen with other cell types), air bronchograms may be seen radiographically within the tumor.

Tumor Location Symptoms related to the local intrathoracic effect of the primary tumor can be conveniently divided into two groups: pulmonary and nonpulmonary thoracic.

Pulmonary Symptoms. Pulmonary symptoms result from the direct effect of the tumor on the bronchus or lung tissue. Symptoms (in order of frequency) include cough (secondary to irritation or compression of a bronchus), dyspnea (usually due to central airway obstruction or compression, with or without atelectasis), wheezing (with narrowing of a central airway of greater than 50%), hemoptysis (typically, blood streaking of mucus that rarely is massive, and indicates a central airway location), pneumonia (usually due to airway obstruction by the tumor), and lung abscess (due to necrosis and cavitation, with subsequent infection). Nonpulmonary Thoracic Symptoms. Nonpulmonary thoracic symptoms result from invasion of the primary tumor directly into a contiguous structure (e.g., chest wall, diaphragm, pericardium, phrenic nerve, recurrent laryngeal nerve, superior vena cava, and esophagus), or from mechanical compression of a structure (e.g., esophagus or superior vena cava) by enlarged tumor-bearing lymph nodes.

Table 18-2 Clinical Presentation of Lung Cancer Category

Symptom

Cause

Pulmonary symptoms

Cough Dyspnea Wheezing Hemoptysis Pneumonia

Bronchus irritation/compression Airway obstruction/compression >50% Airway obstruction Tumor erosion/irritation Airway obstruction

Nonpulmonary thoracic symptoms

Pleuritic pain Local chest wall pain Radicular chest pain Pancoast syndrome

Parietal pleural irritation/invasion Rib and/or muscle involvement Intercostal nerve involvement Stellate ganglion, chest wall, brachial plexus involvement Recurrent laryngeal nerve involvement Bulky involved mediastinal lymph nodes Medial-based right upper lobe tumor

Hoarseness Swelling of head and arms

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Peripherally-located tumors (often adenocarcinomas) extending through the visceral pleura lead to irritation or growth into the parietal pleura, and potentially to continued growth into the chest wall structures. Three types of symptoms, depending on the extent of chest wall involvement, are possible: (1) pleuritic pain, from noninvasive contact of the parietal pleura with inflammatory irritation and from direct parietal pleural invasion, (2) localized chest wall pain, with deeper invasion and involvement of the rib and/or intercostal muscles, and (3) radicular pain, from involvement of the intercostal nerve(s). Radicular pain may be mistaken for renal colic in the case of lower lobe tumors invading the posterior chest wall. Tumors (usually adenocarcinomas) originating in the posterior apex of the chest, referred to as superior sulcus tumors, may produce the Pancoast syndrome. Depending on the exact tumor location, symptoms can include apical chest wall and/or shoulder pain (from involvement of the first rib and chest wall), Horner’s syndrome (unilateral enophthalmos, ptosis, miosis, and facial anhidrosis from invasion of the stellate sympathetic ganglion), and radicular arm pain (from invasion of T1, and occasionally C8, brachial plexus nerve roots). Invasion of the primary tumor into the mediastinum may lead to involvement of the phrenic or recurrent laryngeal nerves. The phrenic nerve traverses the thoracic cavity along the superior vena cava and anterior to the pulmonary hilum. Direct invasion of the nerve occurs with tumors of the medial surface of the lung, or with anterior hilar tumors. Symptoms may include shoulder pain (referred), hiccups, and dyspnea with exertion because of diaphragm paralysis. Radiographically, the diagnosis is suggested by unilateral diaphragm elevation on chest x-ray, and can be confirmed by fluoroscopic examination of the diaphragm with breathing and sniffing (the “sniff” test). Recurrent laryngeal nerve (RLN) involvement most commonly occurs on the left side, given the hilar location of the left RLN as it passes under the aortic arch. Paralysis may occur from invasion of the vagus nerve above the aortic arch by a medially-based left upper lobe (LUL) tumor, from invasion of the RLN directly by a hilar tumor, or from invasion by hilar or aortopulmonary lymph nodes involved with metastatic tumor. Symptoms include voice change, often referred to as hoarseness, but more typically a loss of tone associated with a breathy quality, and coughing, particularly when drinking liquids. Superior vena cava (SVC) syndrome most frequently occurs with small-cell carcinoma, with bulky enlargement of involved mediastinal lymph nodes and compression of the SVC. Occasionally, a medially-based right upper lobe (RUL) tumor can produce the syndrome with direct invasion. Symptoms include variable degrees of swelling of the head, neck, and arms; headache; and conjunctival edema. Pericardial invasion may lead to pericardial effusions (benign or malignant), associated with increasing levels of dyspnea and/or arrhythmias, and with the potential to develop pericardial tamponade. Diagnosis requires a high index of suspicion in the setting of a medially-based tumor with symptoms of dyspnea, and is confirmed by CT scan or echocardiography. Direct invasion of a vertebral body produces symptoms of back pain, which is often localized and severe. If the neural foramina are involved, radicular pain may also be present. Involvement of the esophagus is usually secondary to external compression by enlarged lymph nodes involved with metastatic disease, usually with lower lobe tumors. Finally, invasion of the diaphragm by a tumor at the base of a lower lobe may produce dyspnea, pleural effusion, or referred shoulder pain.

Table 18-3 Paraneoplastic Syndromes in Patients with Lung Cancer Endocrine Hypercalcemia (ectopic parathyroid hormone) Cushing’s syndrome Syndrome of inappropriate secretion of antidiuretic hormone Carcinoid syndrome Gynecomastia Hypercalcitoninemia Elevated growth hormone Elevated prolactin, follicle-stimulating hormone, lutenizing hormone Hypoglycemia Hyperthyroidism Neurologic Encephalopathy Subacute cerebellar degeneration Progressive multifocal leukoencephalopathy Peripheral neuropathy Polymyositis Autonomic neuropathy Eaton-Lambert syndrome Optic neuritis Skeletal Clubbing Pulmonary hypertrophic osteoarthropathy Hematologic Anemia Leukemoid reactions Thrombocytosis Thrombocytopenia Eosinophilia Pure red cell aplasia Leukoerythroblastosis Disseminated intravascular coagulation Cutaneous Hyperkeratosis Dermatomyositis Acanthosis nigricans Hyperpigmentation Erythema gyratum repens Hypertrichosis lanuginosa acquista Other Nephrotic syndrome Hypouricemia Secretion of vasoactive intestinal peptide with diarrhea Hyperamylasemia Anorexia or cachexia

Tumor Biology Lung cancers, both non-small-cell and small-cell, are capable of producing a variety of paraneoplastic syndromes, most often from tumor production and release of biologically active materials systemically (Table 18-3). The majority of such syndromes are caused by small-cell carcinomas, including many endocrinopathies. Paraneoplastic syndromes may produce symptoms even before symptoms are produced by the primary tumor, thereby leading to early diagnosis. Their presence does not influence resectability or the potential to successfully treat the tumor. Symptoms of the syndrome often will abate with successful treatment, and recurrence may be heralded by recurrent paraneoplastic symptoms. Many of the symptoms induced by these syndromes mimic those of the generalized debility caused by metastatic disease. One of the more common paraneoplastic syndromes in patients with SCLC is hypertrophic pulmonary osteoarthropathy (HPO). Clinically, the syndrome is characterized by tenderness and swelling of the ankles, feet, forearms, and hands. It is due to periostitis of the

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A

B

C FIG. 18-16. Pulmonary hypertrophic osteoarthropathy associated with small-cell carcinoma. A . Painful clubbing of the fingers. B . Painful clubbing of the toes (close-up). C . The arrows point to new bone formation on the femur.

fibula, tibia, radius, metacarpals, and metatarsals. Symptoms may be severe and debilitating. Clubbing of the digits may occur with or be independent of HPO in up to 30% of patients with SCLC (Fig. 18-16). Symptoms of HPO may antedate the diagnosis of cancer by months. Radiographically, plain films of the affected areas show periosteal inflammation and elevation. A bone scan demonstrates intense but symmetric uptake in the long bones. Relief is afforded by aspirin or nonsteroidal anti-inflammatory agents and by successful surgical or medical eradication of the tumor. Hypercalcemia occurs in up to 10% of patients with lung cancer and is most often due to metastatic disease. However, 15% of cases are due to secretion of ectopic parathyroid hormone–related peptide, most often with squamous cell carcinoma. A diagnosis of ectopic parathyroid hormone secretion can be made by measuring elevated serum levels of parathyroid hormone; however, the clinician must also rule out concurrent metastatic bone disease by a bone scan. Symptoms of hypercalcemia include lethargy, depressed level of consciousness, nausea, vomiting, and dehydration. Most patients have resectable tumors, and following complete resection the calcium level will normalize. Unfortunately, tumor recurrence is extremely common and may manifest as recurrent hypercalcemia. Endocrinopathies are caused by the release of hormones or hormone analogues into the systemic circulation. Most occur with SCLCs. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs in 10 to 45% of patients with SCLC. Characterized by confusion, lethargy, and possible seizures, it is

diagnosed by the presence of hyponatremia, low serum osmolality, and high urinary sodium and osmolality. Another cause of hyponatremia can be the ectopic secretion of atrial natriuretic peptide (ANP). Cushing’s syndrome is due to production of an adrenocorticotropic hormone (ACTH)-like molecule and occurs principally in patients with SCLC. ACTH production is autonomous and not suppressible by dexamethasone. Immunoreactive ACTH is present in nearly all extracts of SCLC. A high percentage of patients with SCLC have elevated ACTH levels by radioimmunoassay, yet fewer than 5% have symptoms of Cushing’s syndrome. Because the serum elevation of ACTH is rapid, the physical signs of Cushing’s syndrome (e.g., truncal obesity, buffalo hump, striae) are unusual. Symptoms are primarily related to the metabolic consequences of severe hypokalemia, metabolic alkalosis, and hyperglycemia. Diagnosis is made by demonstrating hypokalemia (3 cm in greatest dimension • >Involves main bronchus, ≥2 cm distal to the carina • >Invades the visceral pleura • >Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung T3 Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus 3 cm, or tumor of any size with visceral pleura involved arising more than 2 cm distal to the carina (T2 N0) Stage IIA Tumor ≤3 cm not extended to adjacent organs, with ipsilateral peribronchial and hilar lymph node involvement (T1 N1) Stage IIB Tumor >3 cm not extended to adjacent organs, with ipsilateral peribronchial and hilar lymph node involvement (T2 N1) Tumor invading chest wall, pleura, or pericardium but not involving carina, nodes negative (T3 N0) Stage IIIA Tumor invading chest wall, pleura, or pericardium and nodes in hilum or ipsilateral mediastinum (T3, N1–2) or tumor of any size invading ipsilateral mediastinal or subcarinal nodes (T1–3, N2) Stage IIIB Direct extension to adjacent organs (esophagus, aorta, heart, cava, diaphragm, or spine); satellite nodule same lobe, or any tumor associated with contralateral mediastinal or supraclavicular lymph-node involvement (T4 or N3) Stage IV Separate nodule in different lobes or any tumor with distant metastases (M1)

Table 18-6 Cumulative Percentage of Survival by Stage After Treatment for Lung Cancer Time After Treatment Pathologic Stage pT1N0M0 (n = 511) pT2N0M0 (n = 549) pT1N1M0 (n = 76) pT2N1M0 (n = 288) pT3N0M0 (n = 87)

24 Months

60 Months

86% 76% 70% 56% 55%

67% 57% 55% 39% 38%

in diameter have a significantly better prognosis than tumors 2.0 to 3.0 cm in diameter. The wide range of postoperative 5-year survival rates (5 to 25%) after surgical resection with N2 nodal involvement demonstrates the effect of the number and location of involved nodal stations, and of the presence of extracapsular nodal extension. Such variations within stages should help the surgeon tailor preoperative decision making to individual patients. Tumors confined to one lobe without hilar invasion are nearly always resectable by lobectomy.

Treatment Early-Stage Disease. Early-stage disease is typically defined as stages I and II. In this group are T1 and T2 tumors (with or

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without local N1 nodal involvement), and T3 tumors (without N1 nodal involvement). This group represents a small proportion of the total number of patients diagnosed with lung cancer each year (about 15% of 150,000 patients). The current standard of treatment is surgical resection, accomplished by lobectomy or pneumonectomy, depending on the tumor location. Despite the term “early-stage,” surgery as a single treatment modality remains disappointing. After surgical resection of postoperative pathologic stage IA disease, 5-year survival is only 67% as reported by Mountain in 1997. The figures decline with higher stages. The overall 5-year survival rate for stage I disease as a group is about 65%; for stage II disease it is about 41%. Appropriate surgical procedures for patients with early-stage disease include lobectomy, sleeve lobectomy, and occasionally pneumonectomy with mediastinal lymph node dissection or sampling. Sleeve resection is performed for tumors located at airway bifurcations when an acceptable length bronchial margin cannot be obtained by standard lobectomy. Pneumonectomy is rarely performed; it is indicated primarily for larger central tumors involving the distal main stem bronchus when a bronchial sleeve resection is not possible, and when resection of involved N1 lymph nodes cannot be achieved short of pneumonectomy. The latter circumstance occurs with bulky adenopathy or with extracapsular nodal spread. Pancoast tumor (apical tumor) resection should always be preceded by mediastinoscopy. In general, the treatment of these tumors has evolved to a multimodal approach in which radiation plays a constant role. Typically, an induction radiation dose of 30 to 35 Gy is administered to enhance the probability of complete resection, followed by surgery 4 to 5 weeks later. With this approach, 5-year survival rates of 35% have been achieved. Surgical excision usually includes a portion of the lower trunk of the brachial plexus, the stellate ganglion, and the chest wall, along with lobectomy. With chest wall involvement, en bloc chest wall resection, along with lobectomy, is performed, with or without chest wall reconstruction. For small rib resections or those posterior to the scapula, chest wall reconstruction is usually unnecessary. Larger defects (two rib segments or more) are usually reconstructed with Gore-Tex to provide chest wall contour and stability. T3 tumors with direct invasion of the diaphragm or pericardium are also resected en bloc with the involved structure. If a large portion of the right-sided pericardium is removed, reconstruction with thin Gore-Tex membrane will be required to prevent cardiac herniation and venous obstruction. If a patient is deemed medically unfit for major pulmonary resection due to inadequate pulmonary reserve or other medical conditions, then options include limited surgical resection or radiotherapy. Limited resection, defined as segmentectomy or wedge resection, can only be applied to more peripheral T1 or T2 tumors. Moreover, limited resection is associated with an increased rate of local recurrence and a decreased long-term survival rate, probably due to incomplete resection of occult intrapulmonary lymphatic tumor spread. Alternatively, definitive radiotherapy consisting of a total dose of 60 to 65 Gy has resulted in a 5-year survival rate of about 30% for patients with stage I disease. The role of chemotherapy in early-stage NSCLC is evolving. Postoperative adjuvant chemotherapy previously was of no benefit in multiple prospective randomized trials; however, newer, more effective agents have been of benefit, though the final results of current trials are pending. Similarly, prospective phase II studies have shown a potential benefit for preoperative (or induction) chemotherapy.

Locoregional Advanced Disease. Surgical resection as sole therapy has a limited role in stage III disease. T3N1 tumors

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can be treated with surgery alone and have a 5-year survival rate of approximately 25%. Patients with N2 disease are a heterogeneous group. Patients with clinically evident N2 disease (i.e., bulky adenopathy present on CT scan or mediastinoscopy, with lymph nodes often replaced by tumor) have a 5-year survival rate of 5 to 10% with surgery alone. In contrast, patients with microscopic N2 disease discovered incidentally in one lymph node station after surgical resection have a 5-year survival rate that may be as high as 30%. Surgery generally does not play a role in the care of patients with N3 disease (IIIB); however, it is occasionally appropriate in select patients with a T4 primary tumor (superior vena caval, carinal, or vertebral body involvement) and no N2 or N3 disease. Survival rates remain low for these patients. Definitive radiotherapy as a single modality can cure patients with N2 or N3 disease, albeit in less than 10%. Recent improvement has been seen with three-dimensional conformal radiotherapy and altered fractionation. Such poor results are reflective of the facts that radiotherapy is a locoregional treatment, and that most stage III patients die of systemic disease. Therefore, definitive treatment of stage III disease (when surgery is not felt to be feasible at any time) is usually a combination of chemotherapy and radiation. Two strategies for delivery are available. “Sequential” chemoradiation involves full-dose systemic chemotherapy (i.e., cisplatin combined with a second agent) followed by standard radiotherapy (approximately 60 Gy). The combination of chemotherapy followed by radiation has been shown to improve the 5-year survival rate to 17%, as compared with 6% with radiotherapy alone. An alternative approach, referred to as “concurrent chemoradiation,” is to administer chemotherapy and radiation at the same time. When certain chemotherapeutic agents are given at the same time as radiation, tumor cells become sensitized to the radiation, thus enhancing the radiation effect. The advantages of this approach are improved local control of the primary tumor and associated lymph nodes and a lack of delay in administering radiotherapy. A disadvantage, however, is the necessary reduction in chemotherapy dosage in order to diminish overlapping toxicities, which thereby can potentially lead to undertreatment of systemic micrometastases. Randomized trials have shown a modest 5-year survival benefit as compared with chemotherapy. Preoperative (Induction) Chemotherapy for NSCLC. The use of chemotherapy before possible surgical resection has a number of potential advantages: 1. The tumor’s blood supply is still intact, allowing better chemotherapy delivery and avoiding tumor cell hypoxia (in any residual microscopic tumor remaining postoperatively), which would increase radioresistance. 2. The primary tumor may be downstaged with enhanced resectability. 3. Patients are better able to tolerate chemotherapy before surgery. 4. It functions as an in vivo test of the primary tumor’s sensitivity to chemotherapy. 5. Responders are identified, thereby allowing tailoring of additional therapy. 6. Systemic micrometastases are treated.

Potential disadvantages include: 1. A possible increase in the perioperative complication rate. 2. Definitive surgical therapy may be delayed if the tumor is resistant.

In stage IIIA N2 disease, the response rates to such chemotherapy are high—in the range of 70%. The treatment is generally safe, as it does not cause a significant increase in perioperative morbidity. Two randomized trials have now compared surgery alone for

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Table 18-7 Results of Randomized Trials of Surgery vs. Neoadjuvant Chemotherapy Plus Surgery for Advanced-Stage Non-Small-Cell Lung Cancer Trial Rosell et al, 1994 Surgery (+ XRT) Chemo + Surgery (+ XRT) Roth et al, 1998 Surgery Chemo + Surgery

Patients

Resection Rate (%)

Median Survival (Months)

3-Year Survival Rate (%)

30 29

90 85

8 26

0 29

32 28

66 61

11 64

15 56

Chemo = chemotherapy; XRT = radiation therapy. source: Roth JA, Atkinson EN, Fossella F, et al: Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Lung Cancer 21(1):1, 1998.

patients with N2 disease to preoperative chemotherapy followed by surgery. Both trials were stopped before complete accrual because of a significant increase in survival for the chemotherapy arm. The initially observed survival differences have been maintained up to 3 years and beyond (5-year data not shown) (Table 18-7). Given these results, induction chemotherapy with cisplatin-based regimens (two to three cycles) has become standard for patients with N2 disease. The role of surgery remains to be determined. The use of induction chemotherapy in stage I and II disease is undergoing investigation. Preliminary results from phase II studies have suggested an improvement in survival with preoperative chemotherapy. The question is currently being investigated in a large intergroup, cooperative randomized trial. Surgery in Stage IV Disease. The treatment of patients with stage IV disease is chemotherapy. However, on occasion, patients with a single site of metastasis are encountered, particularly with adenocarcinomas presenting with a solitary brain metastasis. In this highly select group, 5-year survival rates of 10 to 15% can be achieved with surgical excision of the brain metastasis and the primary tumor, assuming it is early-stage.

Small-Cell Lung Carcinoma. Small-cell lung carcinoma (SCLC) accounts for about 20% of primary lung cancers and is not generally treated surgically. These aggressive neoplasms have early widespread metastases. Histologically, they can be difficult to distinguish from lymphoproliferative lesions and atypical carcinoid tumors. Therefore a definitive diagnosis must be established with adequate tissue samples. Three groups of SCLC are recognized: pure small-cell carcinoma (sometimes referred to as oat cell carcinoma), small-cell carcinoma with a large-cell component, and combined (mixed) tumors. Unlike NSCLC, clinical staging of SCLC is broadly defined by the presence of local or distant disease. Patients present without evidence of distant metastatic disease, but often have bulky locoregional disease, termed “limited” SCLC. Most often, the primary tumor is large and associated with bulky mediastinal adenopathy, which may lead to obstruction of the superior vena cava. The other clinical stage, disseminated, usually presents with widely disseminated metastatic disease. Patients in either stage are treated primarily with chemotherapy and radiation. Surgery is appropriate for the rare patient with an incidentally discovered peripheral nodule that is found to be SCLC. If a stage I SCLC is identified after resection, postoperative chemotherapy is usually given. Metastatic Lesions to the Lung. The cause of a new pulmonary nodule(s) in a patient with a previous malignancy can be

difficult to discern. Features suggestive of metastatic disease are multiplicity; smooth, round borders on CT scan; and temporal proximity to the original primary lesion. One must always entertain the possibility that a single new lesion is a primary lung cancer. The probability of a new primary cancer versus metastasis in patients presenting with solitary lesions depends on the type of initial neoplasm. The highest likelihood of a new primary lung cancer is in patients with a history of uterine (74%), bladder (89%), lung (92%), and head and neck (94%) carcinomas. Surgical resection of pulmonary metastases has a role in properly selected patients. General principles of selection include the following: (1) the primary tumor must already be controlled; (2) the patient must be able to tolerate general anesthesia, potential single-lung ventilation, and the planned pulmonary resection; (3) the metastases must be completely resectable according to CT imaging; (4) there must be no evidence of extrapulmonary tumor burden; and (5) alternative superior therapy must be unavailable. The technical aim of pulmonary metastasis resections is complete resection of all macroscopic tumor. In addition, any adjacent structure involved should be resected en bloc (i.e., chest wall, diaphragm, and pericardium). Multiple lesions and/or hilar lesions may require lobectomy. Pneumonectomy is rarely justified or employed. Pulmonary metastasis resection can be approached through a thoracotomy or via VATS techniques. McCormack and colleagues reported their experience at Memorial Sloan-Kettering in a prospective study of 18 patients who presented with no more than two pulmonary metastatic lesions and underwent VATS resection. A thoracotomy was performed during the same operation; if palpation identified any additional lesions, they were resected. The study concluded that the probability that a metastatic lesion will be missed by VATS excision is 56%. The patients in that study were evaluated by standard chest CT scan before the advent of spiral CT scanning. It remains a controversial topic whether metastasis resection should be performed via thoracotomy or VATS. Proponents of an open approach refer to the above referenced study. Proponents of VATS techniques argue that the resolution of spiral CT scanning is so far superior that any data using the old standard CT scan are no longer applicable; they also point to the significantly less pain and faster recovery using VATS. To date, no subsequent prospective study using spiral CT scan has been performed to resolve this clinical dilemma. The best data regarding outcomes of resection of pulmonary metastases come from the International Registry of Lung Metastases (IRLM). The registry was established in 1991 by 18 thoracic surgery departments in Europe, the United States, and Canada, and included data on 5206 patients. About 88% of patients underwent complete resection. Survival analysis at 5, 10 and 15 years (grouping

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Table 18-8 Actuarial Survival Data from the International Registry of Lung Metastases Survival

Complete Resection

Incomplete Resection

5-Year 10-Year 15-Year

36% 26% 22%

13% 7%

all primary tumor types) was performed (Table 18-8). Multivariate analysis showed a better prognosis for patients with germ-cell tumors, osteosarcomas, a disease-free interval over 36 months, and a single metastasis.

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oropharyngeal or gastrointestinal secretions. A secondary lung abscess occurs in patients with an underlying condition such as a partial bronchial obstruction, a lung infarct, or adjacent suppurative infections (subphrenic or hepatic abscesses). The incidence of bacterial lung abscess in the United States has declined significantly over the past 50 years, with a concomitant decrease in the mortality rate from between 30 and 40% to between 5 and 10%. This decrease has been attributed to the development of bactericidal antibiotics. Factors associated with a worse outcome include advanced patient age, prolonged symptoms, comorbid disease, nosocomial infection, and perhaps larger cavity size. More recently, a greater proportion of lung abscesses have been associated with pulmonary malignancies or immunosuppression, resulting in an increase in lung abscesses due to unusual or opportunistic organisms.

Pulmonary Infections Lung Abscess A lung abscess is a localized area of pulmonary parenchymal necrosis caused by an infectious organism; tissue destruction results in a solitary or dominant cavity measuring at least 2 cm in diameter. Less often, there may be multiple, smaller cavities (38.9◦ C), chills, leukocytosis (>15,000 cells/ mm3 ), weight loss, fatigue, malaise, pleuritic chest pain, and dyspnea. Lung abscesses may also present in a more indolent fashion, with weeks to months of cough, malaise, weight loss, low-grade fever, night sweats, leukocytosis, and anemia. After aspiration pneumonia, 1 to 2 weeks typically elapse before cavitation occurs; 40 to 75% of such patients produce a putrid,

foul-smelling sputum. Severe complications such as massive hemoptysis, endobronchial spread to other portions of the lungs, rupture into the pleural space and development of pyopneumothorax, or septic shock and respiratory failure are rare in the modern antibiotic era. The mortality rate is about 5 to 10%, except in the presence of immunosuppression, where rates range from 9 to 28%. The chest radiograph is the primary tool for diagnosing a lung abscess (Fig. 18-21). Its distinguishing characteristic is a density

B A

FIG. 18-21. Lung abscess resulting from emesis and aspiration after an alcoholic binge. A . Chest x-ray showing an abscess cavity in the left upper lobe. B . A coronal tomogram highlights the thin wall of the abscess. C . Healing of the abscess cavity after 4 weeks of antibiotic therapy and postural drainage.

C

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or mass with a relatively thin-walled cavity. Frequently, an air-fluid level is observed within the abscess, indicating a communication with the tracheobronchial tree. A CT scan is useful to clarify the diagnosis when the radiograph is equivocal, to help rule out endobronchial obstruction, and to look for an associated mass or other pathologic anomalies. A cavitating lung carcinoma is frequently mistaken for a lung abscess. Other possible differential diagnoses include loculated or interlobar empyema, infected lung cysts or bullae, tuberculosis, bronchiectasis, fungal infections, and noninfectious inflammatory conditions (e.g., Wegener’s granulomatosis). The specific etiologic organism must be identified, ideally before antibiotic administration. Routine sputum cultures may be of limited usefulness because of contamination with upper respiratory tract flora. Bronchoscopy is essential to rule out endobronchial obstruction, which is usually due to a tumor, but occasionally is due to a foreign body. During bronchoscopy, uncontaminated cultures may be obtained by means of bronchoalveolar lavage. Culture samples can also be obtained by percutaneous, transthoracic FNA under ultrasound or CT guidance.

Management. Systemic antibiotics directed against the causative organism represent the mainstay of therapy. For community-acquired infections secondary to aspiration, likely pathogens are oropharyngeal streptococci and anaerobes. Penicillin G, ampicillin, or amoxicillin are the main therapeutic agents, but a beta-lactamase inhibitor or metronidazole should be added to cover the increasing prevalence of gram-negative anaerobes that produce beta-lactamase. Clindamycin is also a primary therapeutic agent. For hospital-acquired infections, Staphylococcus aureus and aerobic gram-negative bacilli are common organisms of the oropharyngeal flora. Piperacillin or ticarcillin with a beta-lactamase inhibitor (or equivalent alternatives) provide better coverage of likely pathogens. The duration of antimicrobial therapy is variable: 1 to 2 weeks for simple aspiration pneumonia and 3 to 12 weeks for necrotizing pneumonia and lung abscess. It is likely best to treat until the cavity is resolved or until serial radiographs show significant improvement. Parenteral therapy is generally used until the patient is afebrile and able to demonstrate consistent enteral intake. Oral therapy may then be needed. Surgical drainage of lung abscesses is uncommon since drainage usually occurs spontaneously via the tracheobronchial tree. Indications for intervention include failure of medical therapy; an abscess under tension; an abscess increasing in size during appropriate treatment; contralateral lung contamination; an abscess larger than 4 to 6 cm in diameter; necrotizing infection with multiple abscesses, hemoptysis, abscess rupture, or pyopneumothorax; and inability to exclude a cavitating carcinoma. External drainage may be accomplished with tube thoracostomy, percutaneous drainage, or surgical cavernostomy. The choice between thoracostomy and radiologically-placed catheter drainage depends on the treating physician’s preference and the availability of interventional radiology. Surgical resection is required in fewer than 10% of lung abscess patients. Lobectomy is the preferred intervention for bleeding from a lung abscess or pyopneumothorax. An important intraoperative consideration is to protect the contralateral lung with a double-lumen tube, bronchial blocker, or contralateral main stem intubation. Surgical treatment has a 90% success rate, with an associated mortality of 1 to 13%.

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segments or it may be diffuse throughout the bronchial tree, typically affecting the medium-sized airways. Overall, this is a rare clinical entity in the United States with a prevalence of less than 1 in 10,000.

Pathogenesis. Development of bronchiectasis can be attributed to either congenital or acquired causes. The principal congenital diseases that lead to bronchiectasis include cystic fibrosis, primary ciliary dyskinesia, and immunoglobulin deficiencies (e.g., selective IgA deficiency). Congenital causes tend to produce a diffuse pattern of bronchial involvement. Acquired causes are categorized broadly as infectious and inflammatory. Adenoviruses and influenza viruses are the predominant childhood viral infections associated with the development of bronchiectasis. Chronic infection with tuberculosis remains an important worldwide cause of bronchiectasis. More significant in the United States is the occurrence of nontuberculous mycobacterial infections causing bronchiectasis, particularly Mycobacterium avium complex. Noninfectious causes of bronchiectasis include inhalation of toxic gases such as ammonia, which results in severe and destructive airway inflammatory responses. Allergic bronchopulmonary aspergillosis, Sj¨ogren’s syndrome, and alpha1 -antitrypsin deficiency are some additional examples of presumed immunologic disorders that may be accompanied by bronchiectasis. The common pathway shared by all of these causes of bronchiectasis is impairment of airway defenses or deficits in immunologic mechanisms that permit bacterial colonization and establishment of chronic infection. Both the bacterial organisms and the inflammatory cells recruited to thwart the bacteria elaborate proteolytic and oxidative molecules, which progressively destroy the muscular and elastic components of the airway walls; those components are then replaced by fibrous tissue. Thus chronic airway inflammation is the essential pathologic feature of bronchiectasis. The dilated airways are usually filled with thick purulent material; more distal airways are often occluded by secretions or obliterated by fibrous tissue. The vascularity of affected bronchial walls increases, bronchial arteries become hypertrophied, and abnormal anastomoses form between the bronchial and pulmonary arterial circulation. There are three principal types of bronchiectasis, based on pathologic morphology: cylindrical—uniformly dilated bronchi, varicose—an irregular or beaded pattern of dilated bronchi, and saccular (cystic)—peripheral balloon-type bronchial dilation. The saccular type is the most common after bronchial obstruction or infection (Fig. 18-22).

Bronchiectasis Bronchiectasis is defined as a pathologic and permanent dilation of bronchi. This condition may be localized to certain bronchial

FIG. 18-22. Multiple cystic-type bronchiectatic cavities can be seen on a cut section of right lower lobe lung.

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Clinical Manifestations and Diagnosis. A daily persistent cough and purulent sputum production are the typical symptoms of bronchiectasis. The quantity of daily sputum production (10 mL to >150 mL) tends to correlate with disease extent and severity. Often, patients with bronchiectasis may appear asymptomatic or have a dry nonproductive cough (“dry bronchiectasis”). These patients are prone to have involvement of the upper lobes. The clinical course is characterized by progressive symptoms and respiratory impairment. Increasing resting and exertional dyspnea are the result of progressive airway obstruction. Acute exacerbations may be triggered by viral or bacterial pathogens. Hemoptysis may become more frequent as the disease progresses, and bleeding is attributable to chronically inflamed, friable airway mucosa. In more advanced stages, massive bleeding may result from erosions of the hypertrophied bronchial arteries. The current gold standard of diagnosis is chest CT scanning, which affords a highly-detailed, cross-sectional view of bronchial architecture. Both mild and severe forms of bronchiectasis are readily demonstrated with this imaging modality. A chest radiograph, although less sensitive, may reveal characteristic signs of bronchiectasis such as lung hyperinflation, bronchiectatic cysts, and dilated, thick-walled bronchi forming tram track–like patterns radiating from the lung hila. Sputum culture may identify characteristic pathogens including H. influenzae, S. pneumoniae, and P. aeruginosa. Sputum acid-fast bacillus smears and cultures should be performed to evaluate for the presence of nontuberculous mycobacteria, which may be common in this setting. The severity of airway obstruction should be determined with spirometry, which can also evaluate the course of disease. Management. Standard therapy includes optimization of secretion clearance from the tracheobronchial tree, use of bronchodilators to reverse any airflow limitation, and correction of reversible underlying causes whenever possible. Chest physiotherapy based on vibration, percussion, and postural drainage is widely accepted as the basis for therapy. Acute exacerbations should be treated with courses of broad-spectrum antibiotics tailored to culture and sensitivity profiles. Usually, a 2- to 3-week course of intravenous antibiotics, followed by an oral regimen, will result in a longer-lasting remission. Surgical resection of a localized bronchiectatic segment or lobe may benefit patients with refractory symptoms while on maximal medical therapy. Multifocal disease must be excluded before any attempt at surgery; any uncorrectable predisposing factor (e.g., ciliary dyskinesia) also must be excluded. An important surgical tenet is to conserve as much normal parenchyma as possible. Patients with end-stage lung disease from bronchiectasis may be potential candidates for a bilateral lung transplant. Surgical resection is also indicated in patients with large hemoptysis secondary to hypertrophied bronchial arteries. Because resection may not always be clinically practical, bronchial artery embolization is an alternative. Mycobacterial Infections Epidemiology. Approximately 8 million new cases of tuberculosis are reported annually worldwide, which result in approximately 3 million deaths—more than for any other single infectious disease. In the United States, infection by mycobacteria is also a significant health problem, with an estimated 3 to 4% of infected individuals developing active disease within the first year, and 5 to 15% of all patients thereafter. During the 1980s the incidence of tuberculosis resurged, primarily related to the emergence of the acquired immunodeficiency syndrome (AIDS). More than 20,000 new cases of tuberculosis currently are reported annually in the United States.

More often, the elderly, minorities, and recent immigrants have clinical manifestations of infection, yet no age group, sex, or race is exempt from infection. In most large urban centers, reported cases of tuberculosis are more numerous among the homeless, prisoners, and drug-addicted populations. Immunocompromised patients additionally contribute to an increased incidence of tuberculosis infection, often developing unusual systemic as well as pulmonary manifestations. As compared with past decades, presently surgical intervention is required more frequently in patients with multipledrug resistant tuberculosis organisms (MDRTB) who do not respond to medical treatment, and in selected patients with nontuberculous mycobacterial infections (NTM).

Microbiology. Mycobacterial species are obligate aerobes. They are primarily intracellular parasites with slow rates of growth. Their defining characteristic is the property of acid-fastness, which is the ability to withstand decolorization by an acid-alcohol mixture after being stained. Mycobacterium tuberculosis is the highly virulent bacillus of this species that produces invasive infection among humans, principally pulmonary tuberculosis. Because of improper application of antimycobacterial drugs and multifactorial interactions, MDRTB organisms have emerged that are defined by their resistance to two or more first-line antimycobacterial drugs. Approximately 10% of new tuberculosis cases, and as many as 40% of recurrent cases, are attributed to MDRTB organisms. The more important NTM organisms include M. kansasii, M. avium and M. intracellulare complex (MAC), and M. fortuitum. The highest incidence of M. kansasii infection is in midwestern U.S. cities among middle-aged males from good socioeconomic surroundings. MAC organisms are important infections in elderly and immunocompromised patient groups. M. fortuitum infections are common complications of underlying severe debilitating disease. None of these organisms are as contagious as M. tuberculosis. Pathogenesis and Pathology. The main route of transmission is via airborne inhalation of viable mycobacteria. Three stages of primary infection have been described. In the first stage, alveolar macrophages ingest the bacilli. Infected macrophages release chemoattractants to recruit additional macrophages. In the second stage, from days 7 to 21, the bacteria continue to multiply in macrophages. The patient is often asymptomatic. The third stage is characterized by the onset of cell-mediated immunity (CD4+ helper T cells) and delayed-type hypersensitivity. Activated macrophages acquire an increased capacity for bacterial killing. Macrophage death increases, resulting in the formation of a granuloma, the characteristic lesion found on pathologic examination. Tuberculous granulomas are composed of blood-derived macrophages, degenerating macrophages or epithelioid cells, and multinucleated giant cells (which are fused macrophages with nuclei around the periphery), also called Langhans cells. T lymphocytes are found at the periphery of granulomas. Macrophage death results in central caseation. The low oxygen content of this environment inhibits macrophage function and bacillary growth. A Ghon complex is a single, small lung lesion that is often the only remaining trace of a primary infection. The primary infection is usually located in the peripheral portion of the middle zone of the lungs. Reactivation of tuberculosis infection may occur after hydrolytic enzymes liquify the caseum. Typically, the apical and posterior segments of the upper lobes and the superior segments of the lower lobes are involved. Edema, hemorrhage, and mononuclear cell infiltration are also present. The tuberculous cavity may become secondarily

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infected with other bacteria, fungi, or yeasts, all of which may contribute to enhanced tissue destruction. The pathologic changes caused by NTM organisms are similar to those produced by M. tuberculosis. MAC infections not only commonly occur in immunocompromised patients, but also tend to develop in previously damaged lungs. Caseous necrosis is uncommon and is characterized by clusters of tissue macrophages filled with mycobacteria. It has a poor granulomatous response and confinement of immune cell infiltration to the interstitium and alveolar walls. Cavitary disease is infrequent, though nodules may be noted.

Clinical Presentation and Diagnosis. The clinical course of infection and the presentation of symptoms are influenced by many factors, including the site of primary infection, the stage of disease, and the degree of cell-mediated immunity. About 80 to 90% of tuberculosis patients present with clinical disease in the lungs. In 85 to 90% of these patients, involution and healing occur, leading to a dormant phase that may last a lifetime. The only evidence of tuberculosis infection may be a positive skin reaction to tuberculin challenge or a Ghon complex observed on chest radiograph. Within the first 2 years of primary infection, reactivation may occur in up to 10 to 15% of infected patients. In 80%, reactivation occurs in the lungs; other reactivation sites include the lymph nodes, pleura, and the musculoskeletal system. After primary infection, pulmonary tuberculosis is frequently asymptomatic. Systemic symptoms of low-grade fever, malaise, and weight loss are subtle and may go unnoticed. A productive cough may develop, usually after tubercle cavitation. Many radiographic patterns can be identified at this stage, including local exudative lesions, local fibrotic lesions, cavitation, bronchial wall involvement, acute tuberculous pneumonia, bronchiectasis, bronchostenosis, and tuberculous granulomas. Hemoptysis often develops from complications of disease such as bronchiectasis or erosion into vascular malformations associated with cavitation. Extrapulmonary involvement is due to hematogenous or lymphatic spread from pulmonary lesions. Virtually any organ can become infected, giving rise to the protean manifestations of tuberculosis. Of note to the thoracic surgeon, the pleura, chest wall, and mediastinal organs may all be involved. More than one-third of immunocompromised patients have disseminated disease, with hepatomegaly, diarrhea, splenomegaly, and abdominal pain. The definitive diagnosis of tuberculosis requires identification of the mycobacterium in a patient’s bodily fluids or involved tissues. Skin testing using purified protein derivative is important for epidemiologic purposes, and can help exclude infection in uncomplicated cases. For pulmonary tuberculosis, sputum examination is inexpensive and has a high diagnostic yield. Bronchoscopy with alveolar lavage may also be a useful diagnostic adjunct and has high diagnostic accuracy. Chest CT scan can delineate the extent of parenchymal disease. Management. Medical therapy is the primary treatment of pulmonary tuberculosis and is often initiated before a mycobacterial pathogen is definitively identified. Combinations of two or more drugs are routinely used in order to minimize resistance, which inevitably develops with only single-agent therapy. First-line drugs include isonicotinic acid hydrazine (isoniazid; INH), ethambutol, rifampin, and pyrazinamide. Second-line drugs include cycloserine, ethionamide, kanamycin, ciprofloxacin, and amikacin, among others. The initial therapy for patients with active pulmonary tuberculosis consists of various drug regimens lasting from 6 to 9 months. Bacterial sensitivity profiles help to tailor drug therapy. In the case of

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MDRTB organisms, four or more antimycobacterial drugs are often used, generally for 18 to 24 months. Rifampin and INH augmented with one or more second-line drugs are most commonly used to treat NTM infections. Generally, therapy lasts about 18 months. The overall response rate is unsatisfactory in 20 to 30% of patients with M. kansasii infection, though most such patients do not require surgical intervention. In contrast, pulmonary MAC infections respond poorly, even to combinations of four or more drugs, thus most such patients become surgical candidates. Overall, sputum conversion is achieved in only 50 to 80% of NTM infections, and relapses occur in up to 20% of patients. In the United States, surgical intervention is most often required in order to treat patients with MDRTB organisms whose lungs have been destroyed and who have persistent thick-walled cavitation. The indications for surgery related to mycobacterial pulmonary infections are as follows: (1) complications resulting from previous thoracic surgery to treat tuberculosis; (2) failure of optimized medical therapy (e.g., progressive disease, lung gangrene, or intracavitary aspergillosis superinfection); (3) tissue acquisition for a definitive diagnosis; (4) complications of pulmonary scarring (e.g., massive hemoptysis, cavernomas, bronchiectasis, or bronchostenosis); (5) extrapulmonary thoracic involvement; (6) pleural tuberculosis; and (7) NTM infections. The governing principle of mycobacterial surgery is to remove all gross disease while preserving any uninvolved lung tissue. Scattered nodular disease may be left intact, given its low mycobacterial burden. Antimycobacterial medications should be given preoperatively (for about 3 months) and continued postoperatively for 12 to 24 months. Overall, more than 90% of patients who were deemed good surgical candidates are cured when appropriate medical and surgical therapy is used.

Actinomycetic Infections Actinomycosis. Members of the families Actinomycetaceae and Nocardiaceae were once considered fungi, but now are classified as bacteria. Actinomycosis is a chronic disease usually caused by Actinomyces israelii. It is characterized by chronic suppuration, sinus formation, and discharge of purulent material containing yellow-brown sulfur granules. About 15% of infections involve the thorax; organisms enter the lungs via the oral cavity (where they normally reside) of humans. The diagnosis is challenging because the disease is uncommon and thus not often suspected and appropriately cultured under anaerobic conditions. Lung involvement can present with progressive pulmonary fibrosis in the periphery. Pleural and chest wall involvement (periostitis of the ribs) is an associated finding. Prolonged, high-dose penicillin is effective. Because of an intense fibrotic reaction surrounding affected parenchyma, surgery is seldom possible. Nocardiosis. Nocardia asteroides is an aerobic, acid-fast, gram-positive organism that usually causes nocardiosis, a disease similar to actinomycosis with additional CNS involvement. Additionally, hematogenous dissemination from a pulmonary focus may lead to generalized systemic infection. The disease process ranges from benign, self-limited suppuration of skin and subcutaneous tissues, to pulmonary (extensive parenchymal necrosis and abscesses) and systemic (e.g., CNS) manifestations. In immunosuppressed patients, pulmonary cavitation or hematogenous dissemination may be accelerated. Prolonged treatment (2 to 3 months) with sulfadiazine, minocycline, or trimethoprim-sulfamethoxazole is typically required. Surgery to drain abscesses and empyema is indicated.

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Pulmonary Mycoses An important differential diagnosis to consider in thoracic pathology in general is a mycotic lung infection that can mimic a bronchial carcinoma or tuberculosis. Most fungi are secondary or opportunistic pathogens that cause pulmonary and systemic infections in humans only when natural host resistance is impaired. Clinically significant examples include species of Aspergillus, Cryptococcus, Candida, and Mucor. However, some fungi are primary or true pathogens, able to cause infections in otherwise healthy patients. Some endemic examples in the United States include species of Histoplasma, Coccidioides, and Blastomyces. The incidence of fungal infections has increased significantly, with many new opportunistic fungi emerging. This increase is attributed to the growing population of immunocompromised patients (i.e., organ transplant recipients, cancer patients undergoing chemotherapy, human immunodeficiency virus [HIV] patients, and young and elderly patients) who are more likely to become infected with fungi. Other at-risk patient populations include those who are malnourished, severely debilitated, diabetic, or who have hematologic disorders. Patients receiving high-dose, intensive antibiotic therapy are also susceptible. Fungal infections are definitively diagnosed by directly identifying the organism in body exudates or tissues, preferably grown in culture. Serologic testing to identify mycotic-specific antibodies may also be a useful diagnostic tool. Several new classes of antifungal agents are now available that are effective against many life-threatening fungi and are less toxic than older agents. Thoracic surgery may be a useful therapeutic adjunct for patients with pulmonary mycoses.

Aspergillosis. The genus Aspergillus comprises over 350 species, three of which are most commonly responsible for clinical disease: A. fumigatus, A. flavus, and A. niger. Aspergillus is a saprophytic, filamentous fungus with septate hyphae. Spores (2.5 to 3 µm in diameter) are released and easily inhaled by susceptible patients; the spores then are able to reach the distal bronchi and alveoli. Aspergillosis can manifest as one of three clinical syndromes: Aspergillus hypersensitivity lung disease, aspergilloma, or invasive pulmonary aspergillosis. Overlap occurs between these syndromes, depending on the patient’s immune status. Hypersensitivity results in productive cough, fever, wheezing, lung infiltrates, eosinophilia, and elevation of IgE antibodies to Aspergillus. Aspergilloma (fungal ball) tends to colonize preexisting cavities and is a matted sphere of hyphae, fibrin, and inflammatory cells, that grossly appears as a round or oval, friable, gray (or red, brown, or even yellow), necrotic-looking mass (Fig. 18-23). This form is the most common presentation of (noninvasive) pulmonary aspergillosis. The clinical features vary, with some patients remaining asymptomatic. Hemoptysis is most commonly associated with aspergilloma, followed by chronic and productive cough, clubbing, malaise, or weight loss. Sometimes the diagnosis is suggested by a routine chest radiograph, on which a crescentic radiolucency above a rounded radiopaque lesion (Monad sign) is observed. Therapy should be individualized; asymptomatic aspergilloma does not require treatment. For mild, non-life-threatening hemoptysis, initial treatment can be medical management. Amphotericin B is the drug of choice. Indications for surgical intervention include recurrent or massive hemoptysis, chronic cough with systemic symptoms, progressive infiltrate around the mycetoma, and a pulmonary mass of unknown cause. The goal of surgery is to encompass all diseased tissue with a limited pulmonary resection. The postresectional residual space in the thorax should be obliterated. Techniques

to do so include pleural tent, pneumoperitoneum, decortication, muscle flap, omental transposition, and thoracoplasty. Long-term follow-up is necessary, given that the recurrence rate after surgery is about 7%. Invasive pulmonary aspergillosis typically affects immunocompromised patients who have dysfunctional cellular immunity, namely defective polymorphonuclear leukocytes. Invasion of pulmonary parenchyma and blood vessels by a necrotizing bronchopneumonia may be complicated by thrombosis, hemorrhage, and then dissemination. Patients present with fever that is nonresponsive to antibiotic therapy in the setting of neutropenia. They may also have pleuritic chest pain, cough, dyspnea, or hemoptysis. A chest CT scan, in addition to routine radiography, may reveal finer details of the infective process and characteristic signs (e.g., halo sign and cavitary lesions). Empiric antifungal therapy (using amphotericin B) should be started in these high-risk patients. The mortality rate is high, ranging from 93 to 100% in bone marrow transplant recipients, to approximately 38% in kidney transplant recipients. To minimize the neutropenic period (which contributes to uncontrolled disease), hematopoietic growth factors may be considered. Surgical removal of the infectious nidus is advocated by some groups because medical treatment has such poor outcomes.

Cryptococcosis. Cryptococcosis is a subacute or chronic infection caused by Cryptococcus neoformans, a round, budding yeast (5 to 20 µm in diameter) that is sometimes surrounded by a characteristic wide gelatinous capsule. Cryptococci are typically present in soil and dust contaminated by pigeon droppings. When inhaled, such droppings can cause a nonfatal disease primarily affecting the pulmonary and central nervous systems. At present, cryptococcosis is the fourth most common opportunistic infection in patients with HIV infection, affecting 6 to 10% of that population. Four basic pathologic patterns are seen in the lungs of infected patients: granulomas; granulomatous pneumonia; diffuse alveolar or interstitial involvement; and proliferation of fungi in alveoli and lung vasculature. Symptoms are nonspecific, as are the radiographic findings. Cryptococcus may be isolated from sputum, bronchial washings, percutaneous needle aspiration of the lung, or cerebrospinal fluid. Multiple antifungal agents are effective against C. neoformans, including amphotericin B and the azoles. Candidiasis. Candida organisms are oval, budding cells (with or without mycelial elements) that colonize the oropharynx of many healthy individuals. The fungi of this genus are common hospital and laboratory contaminants. Usually, Candida albicans causes disease in the oral or bronchial mucosa, among other anatomic sites. Other potentially pathogenic Candida species include C. tropicalis, C. glabrata, and C. krusei. An acute or chronic granulomatous reaction may result. Less common is the development of systemic or disseminated infections; these fungi can invade blood vessel walls and multiple tissues. The incidence of Candida infections has increased and they no longer are confined to immunocompromised patients, but now affect patients who are critically ill for prolonged duration, are taking multiple antibiotics long-term, have indwelling vascular catheters (or urinary catheters), sustain recurrent gastrointestinal perforations, or have burn wounds. With respect to the thorax, such patients commonly have candidal pneumonia, pulmonary abscess, esophagitis, and mediastinitis. Amphotericin B, often in combination with 5-fluorocytosine, is a proven therapeutic treatment for Candida tissue infections. In randomized trials, fluconazole has been found to be equally effective with less toxicity. For patients with Candida mediastinitis (which has a mortality rate over 50%),

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A

B

C surgical intervention to d´ebride all infected tissues is required, in addition to prolonged administration of antifungal drugs.

Mucormycosis. The Mucor species, rare members of the class Zygomycetes, are responsible for rapidly fatal disease in immunocompromised patients. Other disease-causing species of the class Zygomycetes include Absidia, Rhizopus, and Mortierella. Characteristic of these fungi are nonseptate, branching hyphae that are difficult to culture. Infection occurs via inhalation of spores. Neutropenia, acidosis, diabetes, and hematologic malignancy all predispose patients to clinical susceptibility. In the lungs, disease consists of blood vessel invasion, thrombosis, and infarction of infected organs. Tissue destruction is significant, along with cavitation and abscess formation. Initial treatment is to correct underlying risk factors and administer amphotericin B, although the optimal

FIG. 18-23. Pulmonary aspergilloma. A . The chest x-ray shows a solid mass within a cavity surrounded by a rim of air between the mass and cavity wall (Monad sign, arrows). B . A cut section shows the “fungus ball” occupying an old, fibrotic cavity. C . Histologic stain reveals characteristic Aspergillus hyphae invading the wall of the cavity.

duration and optimal total dose are unknown. Surgical resection of any localized disease should be performed after initial medical treatment attempts fail.

Primary Fungal Pathogens. Histoplasma capsulatum is a dimorphic fungus existing in mycelial form in soil contaminated by fowl or bat excreta, and in yeast form in human hosts. Histoplasmosis primarily affects the respiratory system after spores are inhaled. It is the most common of all fungal pulmonary infections. In the United States, this disease is endemic in the Midwest and Mississippi River Valley, where about 500,000 new cases arise each year. Active, symptomatic disease is uncommon. Acute forms of the disease present as primary or disseminated pulmonary histoplasmosis; chronic forms present as pulmonary granulomas (histoplasmomas), chronic cavitary histoplasmosis, mediastinal granulomas, fibrosing

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mediastinitis, or broncholithiasis. In immunocompromised patients, the infection becomes systemic and more virulent; because cellmediated immunity is impaired, uninhibited fungal proliferation occurs within pulmonary macrophages and then spreads. Histoplasmosis is definitively diagnosed by fungal smear, culture, direct biopsy of infected tissues, or serologic testing. The clinical presentation depends on the inoculum size and on host factors. Patients with acute pulmonary histoplasmosis commonly present with fever, chills, headache, chest pain, musculoskeletal pain, and nonproductive cough. Chest radiographs may be normal or may show mediastinal lymphadenopathy and patchy parenchymal infiltrates. Most patients improve in a few weeks and do not require antifungal therapy. Amphotericin B is the treatment of choice if moderate symptoms persist for 2 to 4 weeks; if the illness is extensive, including dyspnea and hypoxia; and if patients are immunosuppressed. As the pulmonary infiltrates from acute histoplasmosis heal, consolidation into a solitary nodule or histoplasmoma may occur. This condition is asymptomatic and is usually seen incidentally on radiographs as a coin-shaped lesion. Central calcification may occur; if so, no further treatment is required. Noncalcification of the lesion requires further diagnostic work-up including chest CT scan, needle biopsy, or surgical excision to rule out a malignancy. When lymph nodes and pulmonary granulomas calcify over time, pressure atrophy on the bronchial wall may result in erosion and migration of the granulomatous mass into the bronchus, causing broncholithiasis. Typical symptoms include cough, hemoptysis, and dyspnea. Life-threatening complications include massive hemoptysis or bronchoesophageal fistula. In addition to radiography, bronchoscopy should be performed to aid in diagnosis. Definitive treatment is surgical; the bronchial mass should be removed and any associated complications repaired. Chronic cavitary histoplasmosis occurs in about 10% of patients who become symptomatic after infection. Most such patients have preexisting lung pathology such as COPD or emphysema. Colonization of diseased lung spaces occurs as the ongoing pneumonitis and necrosis that are characteristic of this disease lead to cavity enlargement, new cavity formation, and eventually spread to other areas of lung. Nonspecific symptoms are common, such as cough, sputum production, fever, weight loss, weakness, and hemoptysis. Cavitation, scarring, and partial resolution may be observed on radiographs. Itraconazole or ketoconazole can effectively treat this condition, although more severe infection may require amphotericin B. Surgical excision of localized thick-walled cavities unresponsive to courses of antifungal therapy should be considered if pulmonary reserve is adequate. Disseminated histoplasmosis presents as a spectrum of illness, ranging from nonspecific signs of fever, weight loss, and malaise, to shock, respiratory distress, and multiorgan failure. Use of amphotericin B has decreased the mortality rate to less than 25% in this type of serious infection. Coccidioides immitis is an endemic fungus found in soil and dust of the southwestern United States. Infection results from inhalation of spores (arthroconidia), which individually swell into spherules that later subdivide into endospores. Positive culture results from sputum, other body fluid, or tissue are necessary for a definitive diagnosis. Acute pulmonary coccidioidomycosis occurs in about 40% of people who inhale spores. Symptoms consist of fever, sweating, anorexia, weakness, arthralgia, cough, sputum, and chest pain. When symptoms and radiographic findings persist for more than 6 to 8 weeks, the disease is considered to be persistent coccidioidal pneumonia. Caseous nodules, effusions, pneumonic areas, cavities, and calcified, fibrotic, or ossified lesions may be observed on chest

radiographs. In a small minority of infected patients (0.5%) extrapulmonary disease may develop, with involvement of meninges, bones, joints, skin, or soft tissues. Immunocompromised patients are especially susceptible to disseminated coccidioidomycosis, which carries a mortality rate over 40%. Itraconazole and fluconazole are effective treatments for patients with mild to moderate disease with evidence of pulmonary cavitation or progressive chronic pulmonary lesions. Amphotericin B is warranted for patients with severe pulmonary or disseminated disease and for immunocompromised patients. Surgical resection by lobectomy may be considered if cavities persist for more than 2 years, are larger than 2 cm in diameter, rapidly enlarge, rupture, are thick-walled, or are associated with severe or recurrent hemoptysis. Blastomyces dermatitidis is a round, single-budding yeast with a characteristic thick, refractile cell wall. It primarily infects the lungs of people who inhale contaminated soil that has been disturbed. Cutaneous and disseminated forms of blastomycosis also occur. B. dermatitidis has a worldwide distribution; in the United States it is endemic in the central states. The organism induces a granulomatous and pyogenic reaction with microabscesses and giant cells; caseation, cavitation, and fibrosis may also occur. Symptoms are nonspecific and include cough, mucoid sputum production, chest pain, fever, malaise, weight loss, and hemoptysis. In acute disease, consolidation is usually noted on radiographs; in chronic disease, fibronodular lesions (with or without cavitation) that are similar to tuberculosis are noted. Oral itraconazole for 6 months is the treatment of choice for most patients. Amphotericin B is warranted for patients with cavitary blastomycosis, disseminated disease, or extensive lung involvement and immunocompromised patients. After adequate drug therapy, surgical resection of known cavitary lesions should be considered because viable organisms are known to persist in such lesions.

Antifungals. Limitations in the treatment of fungal pneumonias still exist. Several antifungal agents are available and others are under study. Amphotericin B, a by-product of the actinomycete Streptomyces nodosus, has served as the mainstay for deep, systemic fungal infections. A complex lipophilic organic compound or polyene, amphotericin B binds to ergosterol in the cell membranes of fungi, causing disruption and ion leakage. However, nephrotoxicity limits its usefulness and applicability. Three lipid-based formulations of amphotericin B have now shown decreased nephrotoxicity and higher drug-dose delivery. Higher costs and limited data concerning better efficacy have tempered widespread adoption of these three drugs as first-line antifungal therapy. Susceptible fungi convert 5-fluorocytosine (flucytosine) to 5-fluorouracil, which inhibits DNA and RNA synthesis. Flucytosine is commonly used in combination with amphotericin B in patients with cryptococcal or candidal infections, in order to decrease the amount of amphotericin B necessary. The azole compounds include miconazole, ketoconazole, fluconazole, and itraconazole. This class of drugs inhibits the enzyme cytochrome P450, thereby interfering with fungal cell membrane synthesis; lanosterol is not converted to ergosterol, a necessary fungal component. Echinocandins are a new class of antifungals that inhibit cell wall synthesis by interfering with glucan synthesis. Caspofungin is the first echinocandin to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of invasive pulmonary aspergillosis that is refractory to first-line agents. The most common associated side effects include fever, nausea, vomiting, and infusion-related venous effects. In vitro, it has activity against Candida species, but human clinical trial results have not been published. It is likely

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that this class of antifungals will become an integral part of the management of candidiasis. Newer triazole antifungal agents with improved activity against Aspergillus, Candida, and Histoplasma species have been introduced. Voriconazole is the first such drug to be introduced into the clinical setting. Randomized trials need to be completed to establish its precise clinical applicability. Side effects include hepatotoxicity and visual disturbances.

Massive Hemoptysis Massive hemoptysis is generally defined as expectoration of over 600 mL of blood within a 24-hour period. It is a medical emergency associated with a mortality rate of 30 to 50%. Most clinicians would agree that losing over a liter of blood via the airway within 1 day is significant, yet use of an absolute volume criterion presents difficulties. First, it is difficult for the patient or caregivers to quantify the volume of blood being lost. Second, and most relevant, the rate of bleeding necessary to incite respiratory compromise is highly dependent on the individual’s prior respiratory status. For example, the loss of 100 mL of blood over 24 hours in a 40-year-old male with normal pulmonary function would be of little immediate consequence, because his normal cough would ensure his ability to clear the blood and secretions. In contrast, the same amount of bleeding in a 69-year-old male with severe COPD, chronic bronchitis, and an FEV1 of 1.1 L may be life-threatening.

Anatomy The lungs have two sources of blood supply: the pulmonary and bronchial arterial systems. The pulmonary system is a highcompliance, low-pressure system, and the walls of the pulmonary arteries are very thin and delicate. The bronchial arteries, part of the systemic circulation, have systemic pressures and thick walls; most branches originate from the proximal thoracic aorta. Most cases of massive hemoptysis involve bleeding from the bronchial artery circulation or from the pulmonary circulation pathologically exposed to the high pressures of the bronchial circulation. In many cases of hemoptysis, particularly those due to inflammatory disorders, the bronchial arterial tree becomes hyperplastic and tortuous. The systemic pressures within these arteries, combined with a disease process within the airway and erosion, lead to bleeding.

Causes Significant hemoptysis has many causes, the most common of which are shown in Fig. 18-24. Most are secondary to inflammatory processes. An acute necrotizing pneumonic infection can lead to destruction and erosion of vascular structures and bleeding. Chronic inflammatory disorders (i.e., bronchiectasis, cystic fibrosis, tuberculosis, and others) lead to localized bronchial arterial proliferation, and with erosion, bleeding of these hypervascular areas occurs. Tuberculosis also can cause hemoptysis by erosion of a broncholith (a calcified tuberculous lymph node) into a vessel, or when a tuberculous cavity is present, by erosion of a blood vessel within the cavity. Within such cavities, aneurysms of the pulmonary artery (referred to as Rasmussen’s aneurysm) can develop that are accompanied by subsequent erosion and massive bleeding. Hemoptysis due to lung cancer is usually mild, resulting in bloodstreaked sputum. Massive hemoptysis in patients with lung cancer is typically caused by malignant invasion of pulmonary artery vessels by large central tumors; although rare, it is often a terminal event.

CAUSE OF HEMOPTYSIS

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Number of Deaths

Necrotizing pneumonia

Patients Suffering from the Pathology

Lung cancer

Chronic pulmonary inflammatory diseases 0

5

10

15

20

25

30

NUMBER OF PATIENTS FIG. 18-24. Cause of massive hemoptysis and in-hospital mortality. (Adapted with permission from Jougon J, Ballester M, Delcambre F, et al: Massive hemoptysis: What place for medical and surgical treatment. Eur J Cardiothorac Surg 22:345, 2002.)

Management The treatment of patients with life-threatening hemoptysis is best managed by a multidisciplinary team of intensive care physicians, interventional radiologists, and thoracic surgeons. Treatment priorities are as follows: (1) achieve respiratory stabilization and prevent asphyxiation, (2) localize the bleeding site, (3) stop the hemorrhage, (4) determine the cause, and (5) definitively prevent recurrence. The clinically pragmatic definition of massive hemoptysis is a degree of bleeding that threatens respiratory stability. Therefore clinical judgment of the risk of respiratory compromise is the first step in evaluating a patient. Two scenarios are possible: (1) bleeding is significant and persistent, but its rate allows a rapid but sequential diagnostic and therapeutic approach, and (2) bleeding is so rapid that emergency airway control and therapy are necessary.

Scenario 1: Significant, Persistent, But Nonmassive Bleeding. Although bleeding is brisk in scenario 1, the patient may be able to maintain clearance of the blood and secretions with his or her own respiratory reflexes. Immediate measures are admission to an intensive care unit, strict bedrest, Trendelenburg positioning with the affected side down (if known), administration of humidified oxygen, monitoring of oxygen saturation and arterial blood gases, and insertion of large-bore intravenous catheters. Strict bedrest with sedation may lead to slowing or cessation of bleeding, and the judicious use of intravenous narcotics or other relaxants to mildly sedate the patient and diminish some of the reflexive airway activity is often necessary. Also recommended are administration of aerosolized adrenaline, intravenous antibiotic therapy if needed, and correction of abnormal blood coagulation study results. Finally, unless contraindicated, intravenous vasopressin (20 U over 15 minutes, followed by an infusion of 0.2 U/min) can be given. A chest x-ray is the first test, and often proves to be the most revealing. Localized lesions may be seen, but the effects of blood soiling of other areas of the lungs may predominate, obscuring the area of pathology. Chest CT scan provides more detail and is nearly always performed if the patient is stable. Pathologic areas may be obscured by blood soiling.

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Flexible bronchoscopy is the next step in evaluating the patient’s condition. Some clinicians argue that rigid bronchoscopy should always be performed. However, if the patient is clinically stable and the ongoing bleeding is not imminently threatening, flexible bronchoscopy is appropriate. It allows diagnosis of airway abnormalities and will usually permit localization of the bleeding site to either a lobe or even a segment. The person performing the bronchoscopy must be prepared with excellent suction and must be able to perform saline lavage with a dilute solution of epinephrine. Most cases of massive hemoptysis arise from the bronchial arterial tree; therefore the next therapeutic option frequently is selective bronchial arteriography and embolization. Prearteriogram bronchoscopy is extremely useful to direct the angiographer. However, if bronchoscopy fails to localize the bleeding site, then bilateral bronchial arteriograms can be performed. Typically, the abnormal vascularity is visualized, rather than extravasation of the contrast dye. Embolization will acutely arrest the bleeding in 80 to 90% of patients. However, 30 to 60% of patients will have recurrences. Therefore, embolization should be viewed as an immediate but likely temporizing measure to acutely control bleeding. Subsequently, definitive treatment of the underlying pathologic process is appropriate. If bleeding persists after embolization, a pulmonary artery source should be suspected and a pulmonary angiogram performed. If respiratory compromise is impending, orotracheal intubation should be performed. After intubation, flexible bronchoscopy should be performed to clear blood and secretions and to attempt localization of the bleeding site. Depending on the possible causes of the bleeding, bronchial artery embolization or (if appropriate) surgery can be considered.

Scenario 2: Significant, Persistent, and Massive Bleeding. Life-threatening bleeding requires emergency airway control and preparation for potential surgery. Such patients are best cared for in an operating room equipped with rigid bronchoscopy. Immediate orotracheal intubation may be necessary to gain control of ventilation and suctioning. However, rapid transport to the operating room with rigid bronchoscopy should be facilitated. Rigid bronchoscopy allows adequate suctioning of bleeding with visualization of the bleeding site; the nonbleeding side can be cannulated with the rigid scope and the patient ventilated. After stabilization, ice-saline lavage of the bleeding site can then be performed (up to 1 L in 50-mL aliquots); bleeding stops in up to 90% of patients. Alternatively, blockade of the main stem bronchus of the affected side can be accomplished with a double-lumen endotracheal tube, with a bronchial blocker, or by intubation of the nonaffected side by an uncut standard endotracheal tube. Placement of a double-lumen endotracheal tube is challenging in these circumstances, given the bleeding and secretions. Proper placement and suctioning may be difficult, and attempts could compromise the patient’s ventilation. The best option is to place a bronchial blocker in the affected bronchus with inflation. The blocker is left in place for 24 hours and the area is reexamined bronchoscopically. After this 24-hour period, bronchial artery embolization can be performed.

Surgical Intervention. In most patients, bleeding can be stopped, recovery can occur, and plans to definitively treat the underlying cause can be made. In scenario 1 (significant, persistent, but nonmassive bleeding), the patient may undergo further evaluation as an inpatient or outpatient. A chest CT scan and pulmonary function studies should be obtained preoperatively. In scenario 2 (patients with significant, persistent, and massive bleeding), surgery, if

appropriate, will usually be performed during the same hospitalization as the rigid bronchoscopy or main stem bronchus blockade. In less than 10% of patients, emergency surgery will be necessary, delayed only by efforts to localize the bleeding site by rigid bronchoscopy. Surgical treatment is individualized according to the source of bleeding and the patient’s medical condition, prognosis, and pulmonary reserve. General indications for urgent surgery include (1) presence of a fungus ball, (2) a lung abscess, (3) significant cavitary disease, or (4) failure to control the bleeding. In patients with significant cavitary disease or with fungus balls, the walls of the cavities are eroded and necrotic; rebleeding will likely ensue. In addition, bleeding from cavitary lesions may be due to pulmonary artery erosion, which requires surgery for control.

End-Stage Lung Disease Lung Volume Reduction Surgery Lung volume reduction surgery (LVRS) was originally described by Brantigan in the late 1950s, and the procedure was resurrected and refined by Cooper and associates in 1993. As described by Cooper, the ideal patient for LVRS has heterogeneous emphysema with apical predominance, meaning the worst emphysematous changes are in the apex (seen on chest CT scan) of both lungs. The physiologic lack of function of these areas is demonstrated by quantitative perfusion scan, which shows minimal or no perfusion. By surgically excising these nonfunctional areas, the volume of the lung is reduced, theoretically restoring respiratory mechanics. Diaphragm position and function are improved, and there may be an improvement in the dynamic small airway collapse in the remaining lung. After favorable outcomes were reported from the Barnes experience and other various smaller trials, application of LVRS rapidly escalated. In the mid-1990s, analysis of Medicare claims for LVRS revealed an operative mortality of 16.9% and a 1-year mortality of 23%. In 1997 the National Emphysema Treatment Trial (NETT) conducted a randomized trial of 1218 patients in a noncrossover design to medical versus surgical management after a 10-week pretreatment pulmonary rehabilitation program. Subgroup analysis demonstrated that in patients with the anatomic changes delineated by Cooper and colleagues, LVRS significantly improved exercise capacity, lung function, quality of life, and dyspnea compared to medical therapy. After 2 years, functional improvements began to decline toward baseline. Similar parameters in medically treated patients steadily decline below baseline. LVRS was associated with increased shortterm morbidity and mortality and did not confer a survival benefit over medical therapy.

Lung Transplantation Cooper and associates at the University of Toronto performed the first successful single-lung transplant (SLT) in 1983. Pasque and colleagues introduced the modern technique of a bilateral sequential lung (BSL) transplant in 1990. Today, the most common indications for referral for a lung transplant are COPD and idiopathic pulmonary fibrosis (IPF). Most patients with IPF and older patients with COPD are offered an SLT. Younger COPD patients and patients with alpha1 -antitrypsin deficiency and severe hyperinflation of the native lungs are offered a BSL. Most patients with primary pulmonary hypertension and almost all patients with cystic fibrosis are treated with a BSL. A heartlung transplant is reserved for patients with irreversible ventricular failure or uncorrectable congenital cardiac disease.

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BOS-FREE SURVIVAL

1.0

1.0

0.8

0.8

SURVIVAL

SURVIVAL

OVERALL SURVIVAL

583

0.6 0.4 0.2

0.6 0.4 0.2

1

2

3

1

YEARS POST-TRANSPLANT

2

3

YEARS POST-TRANSPLANT

FIG. 18-25. The overall survival rate after lung transplantation at the University of Minnesota.

FIG. 18-26. The survival rate after lung transplantation in the absence of bronchiolitis obliterans syndrome (BOS) at the University of Minnesota.

Patients with COPD are considered for placement on the transplant waiting list when their forced expiratory volume in 1 second (FEV1 ) has fallen to below 25% of its predicted value. Patients with significant pulmonary hypertension should be listed earlier. IPF patients should be referred when their forced vital capacity has fallen to less than 60%, or their carbon monoxide diffusion capacity (Dlco) to less than 50% of their predicted values. In the past, patients with primary pulmonary hypertension (PPH) and New York Heart Association (NYHA) class III or IV symptoms were listed for a lung transplant. However, treatment of such patients with intravenous prostacyclin and other pulmonary vasodilators has now markedly altered that old strategy. Virtually all patients with PPH are now treated with intravenous epoprostenol. Several of these patients have experienced a marked improvement in their symptoms associated with a decrease in their pulmonary arterial pressures and an increase in exercise capacity. Listing of these patients is deferred until they develop NYHA class III or IV symptoms or until their mean pulmonary artery pressure rises above 75 mm Hg. Medium-term and bronchiolitis obliterans syndrome (BOS)–free survival rates of patients who underwent a lung transplant during a recent 5-year period at the University of Minnesota are shown in Figs. 18-25 and 18-26. The mortality of patients while waiting for transplants is about 10%. In an effort to expand the number of lung donors, many transplant groups have liberalized their criteria for donor selection. Still, the partial pressure of arterial oxygen (Pao2 ) should be greater than 300 mm Hg on a fraction of inspired oxygen (Fio2 ) of 100%. In special circumstances, lungs may be used from donors with a smoking history; from donors older than 50 years of age; and from donors with positive Gram’s stains or infiltrates on chest x-ray. The use of two living donors, each donating a single lower lobe, is another strategy for increasing the donor pool. Recipient outcomes are similar to those with cadaver donors in carefully selected patients. Most of the early mortality after lung transplant is related to primary graft failure resulting from a severe ischemia-reperfusion injury to the lung(s) (Fig. 18-27). Reperfusion injury is characterized radiographically by interstitial and alveolar edema, and clinically by hypoxia and ventilation-perfusion mismatch. Donor neutrophils and recipient lymphocytes probably play an important role in the pathogenesis of reperfusion injury. The most important impediment to longer-term survival after a lung transplant is the development of

bronchiolitis obliterans syndrome (BOS), a manifestation of chronic rejection. Episodes of acute rejection are the major risk factors for developing BOS. Other injuries to the lung (including early reperfusion injury and chronic gastroesophageal reflux disease) may also adversely affect long-term outcomes of patients.

Spontaneous Pneumothorax Spontaneous pneumothorax is secondary to intrinsic abnormalities of the lung, and the most common cause is rupture of an apical subpleural bleb. The cause of these blebs is unknown, but they occur more frequently in smokers and males, and they tend to predominate in young postadolescent males with a tall thin body habitus. Treatment is generally chest tube insertion with water seal. If a leak is present and it persists for greater than 3 days, thoracoscopic management (i.e., bleb resection with pleurodesis by talc or pleural abrasion) is performed. Recurrences or complete lung collapse with the first episode are generally indications for thoracoscopic intervention. Other causes are emphysema (rupture of a bleb or bulla), cystic fibrosis, AIDS, metastatic cancer (especially sarcoma), asthma, lung

PRIMARY GRAFT FAILURE 1.0

No PGF

SURVIVAL

0.8 0.6

PGF

0.4 0.2

1

2

3

YEARS POST-TRANSPLANT FIG. 18-27. The survival rate after lung transplantation at the University of Minnesota as a function of primary graft failure (PGF).

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

abscess, and occasionally lung cancer. Management of pneumothorax in these circumstances is often tied to therapy of the specific disease process and may involve tumor resection, thoracoscopic pleurectomy, or talc pleurodesis.

CHEST WALL MASS

CT or MRI or both

CHEST WALL Chest Wall Mass Clinical Approach The overarching goal of any surgeon involved in caring for a patient with a chest wall mass is to not compromise the patient’s survival should the lesion ultimately prove to be malignant. Both general and thoracic surgeons are asked to participate in the evaluation and subsequent managment of chest wall masses. Therefore the participating surgeons must be well versed in the principles of diagnosing and treating chest wall malignancies. If a less experienced surgeon participates as the technical provider of only a biopsy, it is highly likely that the ultimate surgical resection and reconstruction, and worse, the patient’s survival, will be compromised. All chest wall tumors should be considered malignant until proven otherwise. A general approach is outlined in Figs. 18-28 and 18-29 and is discussed in further detail in the following text. Patients with either a benign or malignant chest wall tumor typically present with complaints of a slowly enlarging palpable mass (50 to 70%), chest wall pain (25 to 50%), or both. When a patient notices a mass, it is often several months before medical consultation can be arranged. Masses may also be discovered after a local traumatic event.

Diagnosis is clear; a surgical resection is the primary treatment Lesion < 2.0 cm

Benign Tumors Fibrous Dysplasia Chondroma Osteochondroma Eosinophilic Granuloma

Malignant Tumors Chondrosarcoma

Wide Surgical Excision

FIG. 18-28. Systematic approach for evaluating a chest wall mass. The clinical scenario is uncomplicated and initial imaging studies suggest a clear diagnosis.

CHEST WALL MASS

CT or MRI or both

Diagnosis is NOT clear

Needle Biopsy or Incisional Biopsy

Nonrhabdosarcoma Fibrosarcoma Malignant fibrous histiocytoma Liposarcoma Synovial Cell Sarcoma Desmoid

Osteosarcoma Rhabdomyosarcoma Nonrhabdomyosarcoma PNET/ Ewing's Sarcoma

Preoperative Chemotherapy

Wide Surgical Excision

FIG. 18-29. Systematic approach for evaluating a chest wall mass in which the diagnosis is not unequivocal. A tissue diagnosis is critical in effective management of chest wall masses.

18/CHEST WALL, LUNG, MEDIASTINUM, AND PLEURA

Pain from a chest wall mass is typically localized to the area of the tumor. Pain is more often present (and more intense) with malignant tumors, but it can also be present in up to one-third of patients with benign tumors. With Ewing’s sarcoma, fever and malaise may also be present. Age can provide guidance as to the possibility of malignancy. Patients with benign chest wall tumors are on average 26 years old; the average age for patients with malignant tumors is 40 years old. Overall, the probability of a chest wall tumor being malignant is 50 to 80%.

Evaluation and Management Laboratory evaluations are usually of little help in assessing chest wall masses. In plasmacytoma, there may be monoclonality of one of the immunoglobulins with normal levels of other immunoglobulins. Another exception is osteosarcoma, in which alkaline phosphatase levels may be elevated. Still another exception is Ewing’s sarcoma, in which the erythrocyte sedimentation rate may be elevated.

Radiography. Radiographic evaluation begins with a chest x-ray, which may reveal evidence of rib destruction, calcification within the lesion, and if old films are available, a clue to growth rate. CT scanning should be done in all patients to evaluate the nature of the primary lesion, to determine its relationship to contiguous structures (e.g., mediastinum, lung, soft tissues, and other skeletal elements), and to search for possible pulmonary metastases. Importantly, contiguous involvement of underlying lung or other soft tissues or the presence of pulmonary metastases does not preclude successful surgery. CT is also valuable in assessing for the presence of extraosseous bone formation and bone destruction, both typically seen with osteosarcoma. MRI has a number of advantages in the radiographic evaluation of chest wall masses, particularly those that may be malignant. Multiple planes of imaging (coronal, sagittal, and oblique) are possible. MRI may also better define the relationship between tumor and muscle. For tumors contiguous to or near neurovascular structures or the spine, MRI and magnetic resonance angiography (MRA) with multiple planes of imaging provides invaluable information about the tumor. Thus it greatly facilitates preoperative planning and may further delineate tissue abnormalities, potentially enhancing the ability to distinguish benign from malignant sarcomas. Biopsy. The first step in the management of all chest wall tumors is to obtain a tissue diagnosis. Inappropriate or misguided attempts at tissue diagnosis through casual open biopsy techniques have the potential (if the lesion is a sarcoma) to seed surrounding tissues and contiguous body cavities (e.g., the pleural space) with tumor cells, potentially compromising local tumor control and patient survival. Accurately typing chest wall sarcomas has a profound impact on their management. Tissue diagnosis can be made by one of three methods: a needle biopsy (typically CT-guided, FNA or a core biopsy), an incisional biopsy, or an excisional biopsy. Until recently, the thoracic surgery literature has been dogmatic in advocating only an excisional biopsy. Reasons for this dogmatic approach were that (1) the entire mass is removed, allowing 100% accurate sampling and diagnosis; (2) compared to incisional biopsy, the potential problem of seeding the surrounding soft tissues with tumor cells does not exist; and (3) adjuvant chemotherapy can be administered. However, management of extremity sarcomas has changed dramatically in the last decade. Neoadjuvant therapy is now the standard of care for certain sarcomas. Since sarcomas of the thorax are

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the same as sarcomas of the extremities, management principles for both should be parallel, whenever technically and medically possible. An excisional biopsy should still be done when the initial diagnosis (based on radiographic evaluation) indicates that it is a benign lesion, or when the lesion has the classic appearance of a chondrosarcoma (in which case definitive surgical resection can be undertaken). Any lesion less than 2.0 cm can be excised as long as the resulting wound is small enough to close primarily. When the diagnosis cannot be made by radiographic evaluation, a needle biopsy (FNA or core) should be done. Pathologists experienced with sarcomas can accurately diagnose approximately 90% of patients using FNA techniques. A needle biopsy (FNA or core) has the advantage of avoiding wound and body cavity contamination (a potential complication with an incisional biopsy). If a needle biopsy is nondiagnostic, an incisional biopsy may be performed, with caveats. When performing an incisional biopsy, the skin incision must be placed directly over the mass and oriented to allow subsequent excision of the scar. Development of skin flaps must be avoided, and in general no drains are used. A drain may be placed if a hematoma is likely to develop, as this can potentially limit soft tissue contamination by tumor cells. Subsequently, if definitive surgical resection is undertaken, the entire area of the biopsy (including skin) must be excised en bloc with the tumor.

Chest Wall Neoplasms Benign Chondroma. Chondromas are one of the more common benign tumors of the chest wall. They are primarily seen in children and young adults. Chondromas usually occur at the costochondral junction anteriorly. Given their typical location and the young age of most patients, chondromas may be confused with costochondritis. Clinically, a mass (usually without pain) is present in the case of chondromas. Radiographically, the lesion is lobulated and radiodense; it may have diffuse or focal calcifications, and may displace the bony cortex without penetration. Chondromas may grow to huge sizes if left untreated. Treatment is surgical resection with a 2-cm margin. One must be certain, however, that the lesion is not a well-differentiated chondrosarcoma. In this case, a wider 4-cm margin is required to prevent local recurrence. Therefore, large chondromas should be treated surgically as low-grade chondrosarcomas. Fibrous Dysplasia. The ribs are a frequent site of origin of fibrous dysplasia. As with chondromas, fibrous dysplasia most frequently occurs in young adults. However, pain is infrequent, and the location is more often in the posterolateral aspect of the rib cage. Fibrous dysplasia may be associated with trauma. Radiographically, an expansile mass is present, with cortical thinning and no calcification. Local excision with a 2-cm margin is curative. Osteochondroma. Osteochondromas are overall the most common benign bone tumor. Many are detected as incidental radiographic findings. Most are solitary; however, patients with multiple osteochondromas have a higher incidence of malignancy. Osteochondromas occur in the first 2 decades of life and they arise at or near the growth plate of bones. The lesions are benign during youth or adolescence. Osteochondromas that enlarge after completion of skeletal growth have the potential to develop into chondrosarcomas. When seen in the thorax they usually arise from the rib cortex and are often part of the autosomal dominant syndrome hereditary

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multiple exostoses. Key features in this circumstance are the known potential to degenerate into chondrosarcomas, which may be heralded by new onset of pain or gradual enlargement of the mass over time. Patients with multiple osteochondromatosis may have benign osteochondromas scattered throughout their rib cage. Thus, the presence of new or increasing localized pain would warrant excisional biopsy of the offending osteochondroma. Local excision of a benign osteochondroma is sufficient. If malignancy is determined, wide excision is performed with a 4-cm margin.

Eosinophilic Granuloma. Eosinophilic granulomas are benign osteolytic lesions. They were originally thought to be destructive lesions with large numbers of eosinophilic cells. Yet eosinophilic granulomas of the ribs can also occur as solitary lesions or as part of a more generalized disease process of the lymphoreticular system termed Langerhans cell histiocytosis (LCH). In LCH, the involved tissue is infiltrated with large numbers of histiocytes (similar to Langerhans cells seen in skin and other epithelia), which are often organized as granulomas. The cause is unknown. Of all LCH bone lesions, 79% are solitary eosinophilic granulomas, 7% involve multiple eosinophilic granulomas, and 14% belong to other forms of more systemic LCH. Isolated single eosinophilic granulomas can occur in the ribs or skull, pelvis, mandible, humerus, and other sites. They are diagnosed primarily in children between the ages of 5 and 15 years. Because of the associated pain and tenderness, they may be confused with Ewing’s sarcoma or with an inflammatory process such as osteomyelitis. Healing may occur spontaneously, but the typical treatment is limited surgical resection with a 2-cm margin. Desmoid Tumors. Desmoid tumors are unusual soft tissue neoplasms that arise from fascial or musculoaponeurotic structures. Histologically, they consist of proliferations of benign-appearing fibroblastic cells, abundant collagen, and few mitoses. Accordingly, some authorities consider desmoid tumors to be a form of fibrosarcoma. Although the cause is unknown, multiple associations with other diseases and conditions are well documented, such as familial polyposis (Gardner syndrome), states of increased estrogen (pregnancy), and trauma. Surgical incisions (abdominal and thorax) have been the site of desmoid development, either in or near the scar. Clinically, patients are usually in the third to fourth decade of life, and have pain, a chest wall mass, or both. The tumor is usually fixed to the chest wall, but not to the overlying skin. No radiographic findings are typical, but MRI may delineate muscle or soft tissue infiltration. Histologic diagnosis may not be possible by a needle biopsy because of low cellularity. An open incisional biopsy for lesions over 3 to 4 cm is often necessary, following the caveats listed above (see biopsy section). Desmoid tumors do not metastasize, but they have a significant propensity to recur locally, with local recurrence rates as high as 5 to 50%, sometimes despite complete initial resection with histologically negative margins. Such locally aggressive behavior is secondary to microscopic tumor infiltration of muscle and surrounding soft tissues. Surgery consists of wide local excision with a margin of 2 to 4 cm, and with intraoperative assessment of resection margins by frozen section. Typically, a rib is removed above and below the tumor with a 4- to 5-cm margin of rib. A margin of less than 1 cm results in much higher local recurrence rates. If a major neurovascular structure would have to be sacrificed, leading to high morbidity, then a margin of less than 1 cm would have to suffice. Survival after wide local excision with negative margins is 90% at 10 years.

Table 18-10 Classification of Sarcomas by Therapeutic Response Tumor Type Osteosarcoma Rhabdomyosarcoma PNET Ewing’s sarcoma MFH Fibrosarcoma Liposarcoma Synovial sarcoma

Chemotherapy Sensitivity + + + + +/− +/− +/− +/−

MFH = malignant fibrous histiocytoma; PNET = primitive neuroectodermal tumor.

Primary Malignant Chest Wall Tumors A wide variety of sarcoma cell types exist. Even though the diagnosis of chest wall tumors is classified by cell type, it is not the primary feature affecting prognosis. Rather, prognosis of sarcomas is determined more by two factors: responsiveness to chemotherapy and histologic grade. Sarcomas can be divided into two broad groups by potential chemotherapeutic responsiveness (Table 18-10). Preoperative (neoadjuvant) chemotherapy offers the ability to (1) assess tumor chemosensitivity by the degree of tumor size reduction and microscopic necrosis, (2) determine which chemotherapeutic agents the tumor is sensitive to, and (3) lessen the extent of surgical resection by reducing tumor size. Patients whose tumors are responsive to preoperative chemotherapy (as judged by the reduction in the size of the primary tumor and/or by the degree of necrosis seen histologically following resection) have a much better prognosis than those with a poor response. Given the tumor’s potential response to chemotherapy or the presence of metastatic disease, the initial treatment is either (1) preoperative chemotherapy (for patients with osteosarcoma, rhabdomyosarcoma, primitive neuroectodermal tumor [PNET], or Ewing’s sarcoma) followed by surgery and postoperative chemotherapy, (2) primary surgical resection and reconstruction (for patients with nonmetastatic malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, or synovial sarcoma), or (3) neoadjuvant chemotherapy followed by surgical resection if indicated in patients presenting with metastatic soft tissue sarcomas. Exceptions to these guidelines may apply at specific centers where the impact of neoadjuvant chemotherapy on soft tissue sarcomas is under investigation. Typically this exception can apply to pediatric patients and to adult patients that have deep, high-grade, nonmetastatic tumors greater than 10 cm in diameter.

Malignant Chest Wall Bone Tumors Chondrosarcoma. Chondrosarcomas are the most common primary chest wall malignancy. As with chondromas, they usually arise anteriorly from the costochondral arches. These slowlyenlarging, often painful masses of the anterior chest wall can reach massive proportions. CT scan shows a radiolucent lesion often with stippled calcifications pathognomonic for chondrosarcomas (Fig. 18-30). The involved bony structures are also destroyed. Metastatic disease to the lungs or bones should be ruled out by CT and bone scan. Most chondrosarcomas are slow growing, low-grade tumors. For this reason, any lesion in the anterior chest wall likely to be a chondroma or a low-grade chondrosarcoma should be treated with wide (4-cm) resection. Chondrosarcomas are not sensitive to

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FIG. 18-30. Chest CT scan showing a right posterior lung tumor. In the appropriate clinical setting, stippled calcifications (white streaks in right lung mass) are highly indicative of chondrosarcomas.

chemotherapy or radiation therapy. Prognosis is determined by tumor grade and extent of resection. With a low-grade tumor and wide resection, patient survival at 5 to 10 years can be as high as 60 to 80%.

Osteosarcoma. Osteosarcomas are the most common bone malignancy, but they are an uncommon malignancy of the chest wall, representing only 10% of all malignant chest wall tumors. They present as rapidly-enlarging, painful masses. Although they primarily occur in young adults, osteosarcomas can occur in patients over the age of 40 years, sometimes in association with previous radiation, Paget’s disease, or chemotherapy. Radiographically, the typical appearance consists of spicules of new periosteal bone formation producing a sunburst appearance. As with chondrosarcomas, careful CT assessment of the pulmonary parenchyma for metastasis is necessary. Osteosarcomas have a propensity to spread to the lungs. Up to one-third of patients present with metastatic disease. Osteosarcomas are potentially sensitive to chemotherapy. Currently, preoperative chemotherapy before surgical resection is common. After chemotherapy, complete resection is performed with wide (4-cm) margins, followed by reconstruction. In patients presenting with lung metastases that are potentially amenable to surgical resection, induction chemotherapy may be given, followed by surgical resection of the primary tumor and of the pulmonary metastases. Following surgical treatment of known disease, additional maintenance chemotherapy is usually recommended. Other Tumors Primitive Neuroectodermal Tumors. PNETs derive from primordial neural crest cells that migrate from the mantle layer of the developing spinal cord. This group of tumors includes neuroblastomas, ganglioneuroblastomas, and ganglioneuromas. Ewing’s sarcomas and Askin’s tumors are closely related to PNETs; together they are referred to as the Ewing’s sarcoma/PNET family of tumors. Askin’s tumors were originally described by Askin in 1979 as a “malignant, small-cell, round tumor of the thoracopulmonary region,” and are now known to be members of the Ewing’s sarcoma/PNET family. Ewing’s sarcomas and PNETs have a common site: a genetic abnormality, a translocation between the long arms of chromosomes 11 and 22. They also share a consistent pattern of proto-oncogene

expression and have been found to express the product of the MIC2 gene. Histologically, they are small-round cell tumors. Ewing’s Sarcoma. Ewing’s sarcomas occur in adolescents and young adults who present with progressive chest wall pain, but without the presence of a mass. Systemic symptoms of malaise and fever are often present. Laboratory studies reveal an elevated erythrocyte sedimentation rate and mild white blood cell elevation. Radiographically, the characteristic onion peel appearance is produced by multiple layers of periosteum in the bone formation. Evidence of bony destruction is also common. The diagnosis can be made by a percutaneous needle biopsy or an incisional biopsy. These tumors have a strong propensity to spread to the lungs and skeleton. Their aggressive behavior produces patient survival rates of only 50% or less at 3 years. Increasing tumor size is associated with decreasing survival. Treatment has improved significantly, now consisting of multiagent chemotherapy, radiation therapy, and surgery. Patients typically are treated preoperatively with chemotherapy; if residual disease is present, they can undergo surgical resection and reconstruction followed by maintenance chemotherapy. Plasmacytoma. Solitary plasmacytomas of the chest wall are very rare, and only 25 to 30 cases are seen annually in the United States. Histologically, the lesion is identical to multiple myeloma, with sheets of plasma cells. It occurs at an average age of 55 years. The typical presentation is pain without a palpable mass. X-rays show an osteolytic lesion. Evaluation for systemic myeloma is performed with bone marrow aspiration, testing of calcium levels, and measurement of urinary Bence Jones proteins. If the results of these studies are negative, then a solitary plasmacytoma is diagnosed. Surgery is usually limited to a biopsy only, which may be excisional. Treatment consists of radiation with doses of 4000 to 5000 cGy. Up to 75% of patients go on to develop systemic multiple myeloma. Patient survival at 10 years is about 20%.

Malignant Chest Soft Tissue Sarcomas Soft tissue sarcomas of the chest wall are uncommon (Fig. 18-31). They include fibrosarcomas, liposarcomas, malignant fibrous histiocytomas (MFHs), rhabdomyosarcomas, angiosarcomas, and other extremely rare lesions. With the exception of

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FIG. 18-31. Chest CT scan showing a right chest wall tumor (arrow). Tissue diagnosis revealed that this mass was a leiomyosarcoma.

rhabdomyosarcomas, the primary treatment of these lesions is wide surgical resection with 4-cm margins and reconstruction. Rhabdomyosarcomas are sensitive to chemotherapy and are often treated with preoperative chemotherapy. As with all sarcomas, soft tissue sarcomas of the chest wall have a propensity to spread to the lungs. The prognosis of such tumors, as noted above, heavily depends on their grade and stage.

Malignant Fibrous Histiocytoma. Malignant fibrous histiocytomas (MFHs) were originally thought to derive from histiocytes, because of the microscopic appearance of cultured tumor cells. Subsequently it was shown that their likely origin is the fibroblast. MFHs are generally the most common soft tissue sarcoma of late adult life, typically occurring between the age of 50 and 70 years, and they are rare under the age of 20. Presentation is pain, with or without a palpable mass. Radiographically, a mass is usually evident, with destruction of surrounding tissue and bone. Treatment is wide resection with a margin of 4 cm or more and reconstruction. Over two-thirds of patients suffer from distant metastasis or local recurrence. Liposarcoma. Liposarcomas make up 15% of chest wall sarcomas. Most liposarcomas are low-grade tumors that have a propensity to recur locally, given their infiltrative nature. Clinically, they present most often as painless masses. Treatment is wide resection and reconstruction. Intraoperative margins should be evaluated (as with all sarcomas) and resection continued, if feasible, until margins are negative. Local recurrence can be treated with reexcision, with occasional use of radiotherapy. Fibrosarcoma. Fibrosarcomas often present as large masses with pain. Radiographically, a mass is seen with surrounding tissue destruction. Treatment is wide local excision with intraopera-

tive frozen-section analysis of margins, followed by reconstruction. Local and systemic recurrence is frequent. Patient survival at 5 years is about 50 to 60%.

Rhabdomyosarcoma. Rhabdomyosarcomas are rare tumors of the chest wall. Microscopically, they are a spindle cell tumor. The diagnosis often depends on immunohistochemical staining for muscle markers. Rhabdomyosarcomas are sensitive to chemotherapy. Treatment consists of preoperative chemotherapy with subsequent surgical resection. Chest Wall Reconstruction The principles of surgery for any malignant chest wall tumor are to strategically plan the anatomy of resection and to carefully assess what structures will need to be sacrificed to obtain a 4-cm margin. Prosthetic reconstruction is usually with 2-mm Gore-Tex, and with appropriate soft-tissue coverage to obtain good coverage of a potentially large defect and to achieve an acceptable cosmetic result. The extent of resection depends on the tumor’s location and on any involvement of contiguous structures. Laterally-based lesions often require simple wide excision, with resection of any contiguously involved lung, pleura, muscle, or skin. Anteriorlybased lesions contiguous with the sternum require partial sternectomy. Primary malignant tumors of the sternum may require complete sternectomy. Posterior lesions involving the rib heads over their articulations with the vertebral bodies may, depending on the extent of rib involvement, require partial en bloc vertebrectomy. Reconstruction of the chest wall can always be accomplished with the use of 2-mm Gore-Tex, attached to the surrounding bony structures with stout sutures of Gore-Tex or polypropylene. GoreTex has become the standard material used in chest wall reconstruction at many institutions for several reasons. It is impervious to fluid, thus preventing pleural fluid from entering the chest wall; it is firm

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and provides excellent rigidity and stability when secured taut to the surrounding bony structures; and it provides a good platform for myocutaneous flap reconstruction. Tissue coverage, except for smaller lesions, invariably involves the use of myocutaneous flaps using the latissimus dorsi, serratus anterior, rectus abdominis, or pectoralis major muscles. In all cases other than small excisions, an experienced plastic surgeon should be engaged with the thoracic surgeon in the preoperative planning and execution of the surgery, in order to ensure optimal physiologic and cosmetic results. Because of the high rate of malignancy of chest wall neoplasms, any mass that likely represents a primary tumor must be aggressively managed. When malignancy is suspected, preliminary plans must be made for chest wall reconstruction that will allow resection of a generous margin of normal tissue around the neoplasm. The resection should include at least one normal adjacent rib above and below the tumor, with all intervening intercostal muscles and pleura. In addition, an en bloc resection of overlying chest wall muscles is often necessary, such as of the pectoralis minor or major, serratus anterior, or latissimus dorsi. When the periphery of the lung is involved with the neoplasm, it is appropriate to resect the adjacent part of the pulmonary lobe in continuity (Fig. 18-32). Involvement of the sternum by a malignant tumor requires total resection of the sternum with the adjacent cartilage. Techniques for postoperative respiratory support are now good enough that resection should not be compromised because of any concern about the patient’s ability to be adequately ventilated in the early postoperative period. Reconstruction of a large defect in the chest wall requires the use of some type of material to prevent lung herniation and to provide stability for the chest wall (see Fig. 18-32). Mild degrees of paradoxical motion are often well tolerated if the area of instability is relatively small. Several authors, notably Pairolero and Arnold from the Mayo Clinic, have reported extensive experience with chest wall reconstruction after removal of significant portions of the bony thorax. They emphasize that adequate resection and dependable reconstruction are essential ingredients to a successful operation. They strongly believe that both a thoracic surgeon and a

FIG. 18-32. Principles of reconstruction after resection of a chest wall tumor (osteogenic sarcoma) is shown. A . En bloc resection of the involved chest wall, including normal ribs above and below the tumor as well as pulmonary parenchyma, must be performed. The resected specimen is shown. B . A prosthesis has been sewn in place. In the lower third of the prosthesis, the line of diaphragm reattachment is seen. The skin defect was closed with a myocutaneous flap from the ipsilateral rectus muscle.

A

589

plastic surgeon must collaborate on these complicated problems. Historically, a wide variety of materials have been used to reestablish chest wall stability, including rib autografts, steel struts, acrylic plates, and numerous synthetic meshes. The current preference is either a 2-mm polytetrafluoroethylene (Gore-Tex) patch or a double-layer polypropylene (Marlex) mesh sandwiched with methyl methacrylate. If soft-tissue coverage is needed, myocutaneous flap reconstruction provides it.

MEDIASTINUM General Concepts Anatomy and Pathologic Entities The mediastinum, the central part of the thoracic cavity, can be divided into compartments for classification of anatomic components and disease processes. There is much overlap, yet this compartmentalization facilitates understanding of general concepts of surgical interest. Several classification schemes exist, but for the purposes of this chapter, the three-compartment model is used (Fig. 1833). This model includes the anterior compartment (often referred to as anterosuperior), the visceral compartment (middle), and the paravertebral sulci bilaterally (posterior compartment). The anterior compartment lies between the sternum and the anterior surface of the heart and great vessels. The visceral or middle compartment is located between the great vessels and the trachea. Posterior to these two compartments lies the paravertebral sulci, bilaterally, and the periesophageal area. The normal content of the anterior compartment includes the thymus gland or its remnant, the internal mammary artery and vein, lymph nodes, and fat. During childhood, the size of the thymus gland is impressive, occupying the entire anterior mediastinum (Fig. 18-34). After adolescence, the thymus gland decreases in both thickness and length and it takes on a more fatty content, with only residual islands of thymic cellular components (Fig. 1835). The middle mediastinal compartment contains the pericardium and its contents, the ascending and transverse aorta, the superior and inferior venae cavae, the brachiocephalic artery and vein, the

B

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

Anterosuperior mediastinum

Posterior mediastinum

Middle mediastinum

FIG. 18-33. Anatomic division of the mediastinum.

phrenic nerves, the upper vagus nerve trunks, the trachea, the main bronchi and their associated lymph nodes, and the central portions of the pulmonary arteries and veins. The posterior compartment contains the descending aorta, esophagus, thoracic duct, azygos and hemiazygos veins, and lymph nodes. Numerous pathologic variants may be present in the various compartments, with much overlap. Table 18-11 includes the most common pathologic entities listed by compartment.

History and Physical Examination The type of mediastinal pathology encountered varies significantly by age of the patient. In adults, the most common tumors include neurogenic tumors of the posterior compartment, benign cysts occurring in any compartment, and thymomas of the anterior

mediastinum (Table 18-12). In children, neurogenic tumors of the posterior mediastinum are also common; lymphoma is the second most common mediastinal tumor, usually located in the anterior or middle compartment; and thymoma is rare (Table 18-13). In both age groups, about 25% of mediastinal tumors are malignant. Pediatric tumors will be discussed in Chap. 38. In most recent series, up to two-thirds of mediastinal tumors in adults are discovered as asymptomatic abnormalities on radiologic studies ordered for other problems. Benign masses are even more likely to be asymptomatic. Characteristics such as size, location, rate of growth, and associated inflammation are important factors that correlate with symptoms. Large, bulky tumors, expanding cysts, and teratomas can cause compression of mediastinal structures, in particular the trachea, and lead to cough, dyspnea on exertion, or stridor. Chest pain or dyspnea may be reported secondary to associated pleural effusions, cardiac tamponade, or phrenic nerve involvement. Occasionally, a mediastinal mass near the aortopulmonary window may be identified in a work-up for hoarseness because of left recurrent laryngeal nerve involvement (Fig. 18-36). The patient in Fig. 18-36 presented with hoarseness and was found to have a primary lung cancer with metastases to the level 5 and 6 lymph nodes in the region of the aortopulmonary window, which led to compression of the left recurrent laryngeal nerve and hoarseness. In the era of screening CT examinations, a higher percentage of malignant tumors of the mediastinum are being discovered as asymptomatic, incidental masses. The history and physical examination in conjunction with the imaging findings may suggest a specific diagnosis. The association of a mediastinal mass, enlarged lymph nodes, and a constitutional symptom such as night sweats or weight loss suggests a lymphoma. An anterior mediastinal mass in the setting of a history of fluctuating weakness and early fatigue or ptosis suggests a thymoma and myasthenia gravis. The neurologic examination may reveal ptosis, diplopia, or proximal muscle weakness, suggesting myasthenia gravis. The physical examination should include a careful search for extrathoracic adenopathy of the cervical, axillary, and inguinal locations. Adenopathy in these locations in association with FIG. 18-34. Normal appearance of the thymus gland in childhood. Ao = aorta; PA = pulmonary artery; VC = vena cava.

Thymus

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591

FIG. 18-35. CT scan of the normal appearance of an involuted thymus gland in an adult. Note the near-total fatty appearance of the gland with only tiny islands of soft tissue scattered within it (small arrows ).

a mediastinal mass suggests a lymphoma. In young adult males, a mediastinal mass and a testicular mass suggest a germ cell tumor. In one recent series, systemic symptoms were present in 50% of patients with a mediastinal mass and a lymphoproliferative disorder, as compared with only 29% of patients with other masses (such as thymic or neurogenic). Laboratory signs of inflammation were also noted: the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated and leukocytosis was present in 86% of patients with a lymphoproliferative disorder, as compared with only 58% of patients with other types of mediastinal masses.

Diagnostic Evaluation Imaging and Serum Markers A number of asymptomatic mediastinal masses are suggested by chest x-rays, but are generally poorly defined by this study. CT has become the most common imaging modality for evaluating mediastinal masses. Contrast-enhanced CT scans for clear delineation of anatomy is preferred. MRI may be indicated in the work-up of a mediastinal mass, particularly in patients contemplating surgical resection. Specifically, MRI is more accurate than CT scan in determining if there is invasion of vascular structures or spinal involvement.

Several other imaging modalities are available to evaluate mediastinal masses of suspected endocrine origin (Table 18-14). Single photon emission computed tomography (SPECT) technology may be used to improve image contrast and give information on three-dimensional localization of some tumors of endocrine origin. SPECT technology has largely replaced conventional twodimensional nuclear imaging studies. If a thyroid origin is suspected, a thyroid scan using 131 I or 123 I can identify most intrathoracic goiters and identify the extent of functioning thyroid tissue. If indicated, the thyroid scan should precede other scans requiring iodine-containing contrast agents, because they would subsequently interfere with iodine tracer uptake by thyroid tissue and scanning. If a pheochromocytoma or neuroblastoma is suspected, the octreotide scan is helpful in diagnosis and localization. The sestamibi scan may be useful for diagnosing and localizing a mediastinal parathyroid gland. PET scanning has improved the noninvasive staging of lung cancer and esophageal cancer. The utility of PET in staging the mediastinum for NSCLC is reviewed in the lung cancer section of this chapter. The utility of PET for staging other tumors of the mediastinum is not as clear. It is useful for distinguishing malignant from benign tumors. It may help detect distant metastases in some patients. For example, in patients with esophageal cancer, up to 10% of those with a negative metastatic survey by conventional imaging

Table 18-11 Usual Location of the Common Primary Tumors and Cysts of the Mediastinum Anterior Compartment

Visceral Compartment

Paravertebral Sulci

Thymoma Germ cell tumor Lymphoma Lymphangioma Hemangioma Lipoma Fibroma Fibrosarcoma Thymic cyst Parathyroid adenoma

Enterogenous cyst Lymphoma Pleuropericardial cyst Mediastinal granuloma Lymphoid hamartoma Mesothelial cyst Neurenteric cyst Paraganglioma Pheochromocytoma Thoracic duct cyst

Neurilemoma-schwannoma Neurofibroma Malignant schwannoma Ganglioneuroma Ganglioneuroblastoma Neuroblastoma Paraganglioma Pheochromocytoma Fibrosarcoma Lymphoma

source: Reproduced with permission from Shields TW: The mediastinum and its compartments, in Mediastinal Surgery. Philadelphia: Lea & Febiger, 1991, p 5.

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Table 18-12 Mediastinal Tumors in Adults Tumor Type

Incidence (%)

Neurogenic tumors Cysts Thymomas Lymphoma Germ cell tumors Mesenchymal tumors Endocrine tumors

21 20 19 13 11 7 6

Location Posterior All Anterior Anterior/middle Anterior All Anterior/middle

source: Reproduced with permission from Shields TW: Primary lesions of the mediastinum and their investigation and treatment, in Shields TW (ed): General Thoracic Surgery, 4th ed. Baltimore: Williams & Wilkins, 1994, p 1731.

including CT scanning, will have a positive PET scan for distant metastases. The role of routine PET imaging for staging surgically resectable lesions of the mediastinum has not been established. The use of serum markers to evaluate a mediastinal mass can be invaluable in some patients. For example, seminomatous and nonseminomatous germ cell tumors can frequently be diagnosed and often distinguished from one another by the levels of alphafetoprotein (AFP) and human chorionic gonadotropin (hCG). In over 90% of nonseminomatous germ cell tumors, either the AFP or the hCG level will be elevated. Results are close to 100% specific if the level of either AFP or hCG is greater than 500 ng/mL. Some centers institute chemotherapy based on this result alone, without a biopsy. In contrast, the AFP level is always normal in patients with mediastinal seminomas; only 10% will have an elevated hCG, which is usually less than 100 ng/mL. Other serum markers, such as intact parathyroid hormone level for ectopic parathyroid adenomas, may be useful for diagnosing and also for intraoperatively confirming complete resection. After successful resection of a parathyroid adenoma, this hormone level should rapidly normalize.

Diagnostic Nonsurgical Biopsies of the Mediastinum The indications and decision-making steps for performing a diagnostic biopsy of a mediastinal mass remain somewhat controversial. In some patients, given noninvasive imaging results and the history, surgical removal may be the obvious choice; preoperative biopsy may be unnecessary and even hazardous. In other patients whose primary treatment is likely to be nonsurgical, a biopsy is essential. Even when a biopsy appears to be a reasonable goal, needle aspiration of the mediastinal mass may be considered hazardous or of low diagnostic yield. Percutaneous biopsy may be technically difficult because of the overlying bony thoracic cavity and the proximity to lung tissue, the heart, and great vessels. FNA biopsy minimizes some of these Table 18-13 Mediastinal Tumors in Children Tumor Type

Incidence (%)

Location

Neurogenic tumors Lymphoma Cysts Germ cell tumors Mesenchymal tumors Thymomas

40 18 18 11 9 Rare

Posterior Anterior/middle All Anterior All Anterior

source: Reproduced with permission from Silverman NA, Sabiston DC Jr.: Mediastinal masses. Surg Clin North Am 60:760, 1980.

FIG. 18-36. A CT scan of a patient who presented with hoarseness due to compression of the left recurrent laryngeal nerve caused by mediastinal lymph node metastases to the aortopulmonary window area from a primary lung cancer.

potential hazards and may be effective in diagnosing mediastinal thyroid tissue, cancers, carcinomas, seminomas, inflammatory processes, and cysts. Other noncarcinomatous malignancies such as lymphoproliferative disorders, thymomas, and benign tumors may require larger pieces of tissue. Such biopsies may be obtained by a core-needle technique (which may not be safe depending on the location of the mass), or by surgery. In light of the issues cited, it is not surprising that the approach to biopsies of mediastinal masses may be different from center to center. Significant controversy exists in the literature regarding this topic. However, the treatment of up to 60% of patients with anterior mediastinal masses is ultimately nonsurgical, so it is essential to understand all options for obtaining adequate tissue for a definitive diagnosis using the least invasive approach. In one recent study, the authors used the medical history, physical examination, laboratory findings (ESR, CRP, and leukocytosis), and CT scan to assign patients to a possible lymphoproliferative diagnosis or a possible nonlymphoproliferative diagnosis. The authors concluded that, if features suggest the lymphoproliferative group of mediastinal masses, the patient should undergo a surgical biopsy, since larger pieces of tissues were required to make the diagnosis in their series. However, if a nonlymphoproliferative diagnosis was suggested, they recommended FNA before a potential surgical resection because the yield of accurate diagnoses by FNA was higher in that group. In 1989, the American Thoracic Society published a position statement that declared that “cutting needles should not be used to biopsy diffuse infiltrative lung diseases or lesions in or adjacent to the mediastinum or hilar areas.” However, since that time, institutions with significant interventional expertise have challenged that statement. In one series of 142 patients with mediastinal masses, CT-guided transthoracic core-needle biopsies were obtained with 14- to 22-gauge needles. The sensitivity was 98.9% with a specificity of 100%. Inadequate material was obtained in only 0.7% of patients, with no pneumothoraces or bleeding complications reported. The diagnostic yield is lower in series including a higher number of patients with lymphoproliferative disorders. Other series also reported a higher complication rate of pneumothorax, ranging from 8 to 23%, and of hemoptysis, up to 10%. In another series of anterior mediastinal masses, Herman reported that needle biopsies were greater

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593

Table 18-14 Nuclear Imaging Relevant to the Mediastinum Radiopharmaceutical, Radionuclide, or Radiochemical

Label

Disease of Interest

Iodine Monoclonal antibodies Octreotide

131 I, 123 I

Gallium Sestamibi

67 Ga

Thallium MIBG Fluorodeoxyglucose

201 Tl

Retrosternal goiter, thyroid cancer Non-SCLC, colon and breast cancer, prostate cancer metastases Amine precursor uptake decarboxylation tumors: carcinoid, gastrinoma, insulinoma, small-cell lung, pheochromocytoma, glucagonoma, medullary thyroid carcinoma, paraganglioma Lymphoma, non-SCLC, melanoma Medullary thyroid carcinoma, nonfunctional papillary or follicular thyroid carcinoma, Hurthle cell thyroid carcinoma, parathyroid adenoma or carcinoma See sestamibi Pheochromocytoma, neuroblastoma, see also octreotide General oncologic imaging, breast and colon cancer, melanoma

111 In, 99m Tc 111 In

99m Tc

131 I, 123 I 18 F

MIBG = metaiodobenzylguanidine; non-SCLC = non-small-cell lung cancer. source: Reproduced with permission from McGinnis KM, Powers CN, Thomas FD, et al: Markers of the mediastinum, in Pearson FG, et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1675.

than 90% specific in diagnosing most carcinomatous tumors, but its accuracy for diagnosing lymphomas was less than 50%. Similar controversy exists regarding the yield of needle biopsies for definitively diagnosing germ cell tumors and thymomas. Knapp described 56 patients with malignant germ cell tumors of the mediastinum. Various combinations of germ cell elements were present in 34% of tumors, so open biopsies with multiple tissue sections were seen as advisable. In another series of 79 patients with mediastinal masses suspected to be malignant, Larsen reported that endoscopic ultrasound-guided FNA had a sensitivity of 92% and a specificity of 100%. CT-guided needle biopsy has proven most useful for investigating tumors that are clearly unresectable or for assessing suspected carcinomatous tumors, in these authors’ experience. For mediastinal masses suggestive of a lymphoma, larger pieces of tissue obtained by mediastinoscopy for sampling paratracheal adenopathy are preferred. Thoracoscopic biopsies are preferred for other locations. If an anterior mediastinal mass appears localized and consistent with a thymoma, surgical resection is performed. Surgical resection without biopsies for most localized tumors of the posterior mediastinum suspected to be neurogenic in origin also is the preference of these authors.

Surgical Biopsies and Resection of Mediastinal Masses For tumors of the mediastinum that are not amenable to a CTguided needle biopsy or that do not yield sufficient tissue for diagnosis, a surgical biopsy is indicated. The definitive approach to a surgical biopsy of the anterior mediastinum is through a median sternotomy. At the time of sternotomy, if the lesion is easily resectable, it should be completely removed. Given the invasiveness of the procedure and the inability in some patients to obtain a definitive diagnosis by frozen section, less invasive procedures are preferable if the lesion is large or if the CT scan or history suggests that surgery is not the best definitive treatment. Masses in the paratracheal region are easily biopsied by mediastinoscopy. For tumors of the anterior or posterior mediastinum, a left or right VATS approach often allows safe and adequate surgical biopsies. In some patients, an anterior mediastinotomy (i.e., Chamberlain procedure) may be ideal for an anterior tumor or a tumor with significant parasternal extension. Before a surgical biopsy is pursued, a discussion should be held with the pathologist regarding routine histologic assessment, special stains and markers, and requirements for lymphoma work-up.

The gold standard for the resection of most mediastinal masses is through a median sternotomy or lateral thoracotomy. In some cases, a lateral thoracotomy with sternal extension (hemi-clamshell) provides excellent exposure for extensive mediastinal tumors that have a lateral component. This standard has been successfully challenged for some anterior mediastinal pathology. For example, good results have been reported using a cervical incision with a sternal retractor for thymus removal. The upward lift allows the surgeon reasonable access to the anterior mediastinum and has proven adequate in some centers for definitive resection of the thymus gland for myasthenia gravis. Similarly, several large series have now shown that a right or left VATS approach can be successful for removal of the thymus gland and for resection of small (1 to 2 cm) encapsulated thymomas. Most would agree that if a larger anterior mediastinal tumor is seen or malignancy is suspected, a median sternotomy with a more radical resection should be performed.

Neoplasms Thymus Thymic Enlargement Thymic Hyperplasia. Diffuse thymic hyperplasia was first described in children after successful chemotherapy for lymphoma. It has now been described in adults and is referred to as “rebound thymic hyperplasia.” It is most frequently reported after chemotherapy for lymphoma or germ cell tumors. Initially, atrophy of the thymic gland is seen; later, on follow-up scans, the patient is noted to have thymic gland enlargement, which can be dramatic. The usual time course for thymic hyperplasia to develop is about 9 months after cessation of chemotherapy, but it has been reported anywhere from 2 weeks to 12 months after chemotherapy. Benign hyperplasia must be clearly distinguished from recurrent lymphoma or germ cell tumors. Doing so may be difficult since thymic hyperplasia is dramatic in some patients, requiring careful follow-up, and at a minimum, serial CT scans. PET scanning may be helpful; a low standardized uptake value of tracer on PET scan suggests a benign tumor, but little has been published on this topic. Biopsies may be required if the clinical index of suspicion is high.

Thymic Tumors Thymoma. Thymoma is the most frequently encountered neoplasm of the anterior mediastinum in adults (seen most frequently

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

between 40 and 60 years of age). They are rare in children. Most patients with thymomas are asymptomatic, but depending on the institutional referral patterns, between 10 and 50% have symptoms suggestive of myasthenia gravis or have circulating antibodies to acetylcholine receptor. However, less than 10% of patients with myasthenia gravis are found to have a thymoma on CT. Thymectomy leads to improvement or resolution of symptoms of myasthenia gravis in only about 25% of patients with thymomas. In contrast, in patients with myasthenia gravis and no thymoma, thymectomy results are superior: up to 50% of patients have a complete remission and 90% improve. In 5% of patients with thymomas, other paraneoplastic syndromes, including red cell aplasia, hypogammaglobulinemia, systemic lupus erythematosus, Cushing’s syndrome, or SIADH may be present. Large thymic tumors may present with symptoms related to a mass effect, which may include cough, chest pain, dyspnea, or superior vena cava syndrome. The diagnosis may be suspected based on CT scan and history, but imaging alone is not diagnostic. In most centers, the diagnosis is made after surgical resection because of the relative difficulty of obtaining a needle biopsy and the likelihood that removal will ultimately be recommended. However, CT-guided FNA biopsy has been reported to have a diagnostic sensitivity of 87% and a specificity of 95% in specialized centers. Cytokeratin is the marker that best distinguishes thymomas from lymphomas. In most patients, the distinction between lymphomas and thymomas can be made on CT scan, since most lymphomas have marked lymphadenopathy and thymomas most frequently appear as a solitary encapsulated mass. The most commonly accepted staging system for thymomas is that of Masaoka. It is based on the presence or absence of gross or microscopic invasion of the capsule and of surrounding structures, as well as on the presence or absence of metastases (Table 18-15). Histologically, thymomas are generally characterized by a mixture of epithelial cells and mature lymphocytes. Grossly, many thymomas remain well encapsulated. Even those with capsular invasion often lack histologic features of malignancy; they appear cytologically benign and identical to early-stage tumors. This lack of classic cellular features of malignancy is why most pathologists use the term “thymomas” or “invasive thymomas” rather than “malignant thymomas.” Thymic tumors with malignant cytologic features are classified separately and referred to as “thymic carcinomas.” The definitive treatment for thymomas is complete surgical removal for all resectable tumors; local recurrence rates and survival vary according to stage (Fig. 18-37). Resection is generally accomplished by median sternotomy with extension to hemi-clamshell in more advanced cases. Even advanced tumors with local invasion of resectable structures such as the pericardium, superior vena cava, or innominate vessels should be considered for resection with reconstruction. VATS resection has been reported for small, encapsulated thymomas, but no large series or long-term results are available to support this approach. The role of adjuvant or neoadjuvant therapies for advanced-stage tumors remains unclear. Traditionally, stage II thymomas have been Table 18-15 Masaoka Classification of Thymoma Staging Stage I: Encapsulated tumor with no gross or microscopic evidence of capsular invasion Stage II: Gross capsular invasion or invasion into the mediastinal fat or pleura or microscopic capsular invasion Stage III: Gross invasion into the pericardium, great vessels, or lung Stage IV a: Pleural or pericardial dissemination Stage IV b: Lymphogenous or hematogenous metastasis

PROPORTION SURVIVING

594

1.0 Stage I

P=.002

.8 Stage IV .6 Stage II .4 Stage III .2 0 0

10

20

YEARS FIG. 18-37. Stage-specific survival for thymomas.

treated by complete surgical resection followed by mediastinal radiation, but due to the relatively small number of cases, randomized trials have not been done. A recent retrospective review of a singleinstitution series of stage II thymoma patients showed no difference in survival or local recurrence after complete surgical resection alone, as compared with surgical resection with radiotherapy. Advanced thymomas have been shown to respond to platinum-based chemotherapy and to corticosteroids. One summary of chemotherapy trials showed an overall response rate of about 70%. Combining radiotherapy and chemotherapy for local progression also has been successful in some small series the combination appears to prolong survival, although most advanced-stage, unresectable thymomas will recur. Therefore it is imperative that all patients with thymomas undergo a thorough evaluation for potential resection. Thymic Carcinoma. Thymic carcinomas are unlike encapsulated or invasive thymomas in that they are unequivocally malignant at the microscopic level. Suster and Rosai classified thymic carcinomas into low-grade and high-grade tumors. Low-grade tumors are well differentiated with squamous cell, mucoepidermoid, or basaloid features. High-grade thymic carcinomas include those with lymphoepithelial, small-cell neuroendocrine, sarcomatoid, clearcell, and undifferentiated or anaplastic features. Compared with thymomas, they are a more heterogeneous group of malignancies with a propensity for early local invasion and widespread metastases. Complete resection is occasionally curative, but most thymic carcinomas will recur and are refractory to chemotherapy. The prognosis of such patients remains poor. Thymolipoma. Thymolipomas are rare benign tumors that may grow to a very large size before being diagnosed. On CT scan, their appearance can be dramatic, with a characteristic fat density dotted by islands of soft tissue density representing islands of thymic tissue (Fig. 18-38). Thymolipomas are generally well-encapsulated, soft, and pliable masses that do not invade surrounding structures. Resection is recommended for large masses.

Neurogenic Tumors Most neurogenic tumors of the mediastinum arise from the cells of the nerve sheath, from ganglion cells, or from the paraganglionic system (Table 18-16). The incidence, cell types, and risk of malignancy strongly correlate with patient age. Tumors of nerve sheath origin predominate in adults. Most present as asymptomatic incidental findings and most are benign. In children and young adults, tumors of the autonomic ganglia predominate, with up to two-thirds being malignant.

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FIG. 18-38. Massive thymolipoma that was asymptomatic in an 18-yearold female.

Nerve Sheath Tumors. Nerve sheath tumors account for 20% of all mediastinal tumors. More than 95% of nerve sheath tumors are benign neurilemomas or neurofibromas. Malignant neurosarcomas are much less common. Neurilemoma. Neurilemomas, also called schwannomas, arise from Schwann cells in intercostal nerves. They are firm, wellencapsulated, and generally benign. Two characteristic histologic components of benign neurilemomas exist and are referred to as Antoni type A and Antoni type B regions. Antoni type A regions contain compact spindle cells with twisted nuclei and nuclear palisading. Antoni type B regions contain loose and myxoid connective tissue with a haphazard cellular arrangement. These characteristics allow them to be distinguished from malignant, fibrosarcomatous tumors, which lack encapsulation and have no Antoni features. If

routine CT scan suggests extension of a neurilemoma into the intervertebral foramen, MRI is suggested to evaluate the extent of this “dumbbell” configuration (Fig. 18-39). Such a configuration may lead to cord compression and paralysis, and requires a more complex surgical approach. It is recommended that most nerve sheath tumors be resected. Traditionally, this have been performed by open thoracotomy but more recently, a VATS approach has been established as safe and effective for simple operations. It is reasonable to follow small, asymptomatic paravertebral tumors in older patients or in patients at high risk for surgery. In children, ganglioneuroblastomas or neuroblastomas are more common; therefore all neurogenic tumors should be completely resected. Neurofibroma. Neurofibromas have components of both nerve sheaths and nerve cells and account for up to 25% of nerve sheath

Table 18-16 Classification of Neurogenic Tumors of the Mediastinum Tumor Origin

Benign

Malignant

Nerve sheath

Neurilemmoma, neurofibroma, melanotic schwannoma, granular cell tumor Ganglioneuroma

Neurofibrosarcoma

Ganglion cell Paraganglionic

Chemodectoma, pheochromocytoma

Ganglioneuroblastoma, neuroblastoma Malignant chemodectoma, malignant pheochromocytoma

source: Reproduced with permission from Bousamra, M: Neurogenic tumors of the mediastinum, in Pearson FG et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1732.

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Ganglion Cell Tumors. Ganglion cell tumors arise from the sympathetic chain or from the adrenal medulla. Histologic cell types include ganglioneuromas, ganglioneuroblastomas, and neuroblastomas. Ganglioneuroma. Ganglioneuromas are well-differentiated, benign tumors that are characterized histologically by welldifferentiated ganglion cells with a background of Schwann cells. They tend to occur in asymptomatic young adults, although diarrhea related to secretion of a vasoactive intestinal peptide has been described. These tumors have a propensity for intraspinal canal extension, although they remain well-encapsulated; complete resection is curative, with a low risk of local recurrence. Ganglioneuroblastoma. Ganglioneuroblastomas contain a mixture of benign ganglion cells and malignant neuroblasts. The distribution of these cells within the tumor is predictive of the clinical course. The nodular pattern is associated with a high incidence of metastatic disease; the diffuse pattern rarely metastasizes. On gross examination, these tumors often remain encapsulated; histologically, there are focal calcifications around regions of neuroblasts. Ganglioneuroblastomas arise most frequently in infants and children under 3 years old. The majority of tumors are resectable, with a 5-year survival rate of 80%. Neuroblastoma. Neuroblastomas are highly malignant. They are the most common extracranial solid malignancy in pediatric patients and the most common intrathoracic malignancy of childhood. The adrenal gland is a common primary site, but 14% of all neuroblastomas arise in the thorax, where the tumors are commonly associated with extension into the spinal canal and osseous invasion. These thoracic tumors are not as recalcitrant to chemotherapy and surgical resection as other chest malignancies; they are more likely to be resectable, with less invasion of surrounding organs. More than half occur in children under 2 years old; 90% arise within the first decade of life and are therefore discussed in more detail in Chap. 38, Pediatric Surgery.

FIG. 18-39. MRI image of a neurogenic tumor with extension into the spinal canal via the foramen, giving a typical dumbbell appearance.

tumors. Up to 40% of patients with mediastinal fibromas have generalized neurofibromatosis (von Recklinghausen’s disease). About 70% of neurofibromas are benign. Malignant degeneration to a neurofibrosarcoma may occur in 25 to 30% of patients. The risk of malignant degeneration increases with advancing age, with von Recklinghausen’s disease, and with exposure to previous radiation. Neurofibrosarcomas carry a poor prognosis because of rapid growth and aggressive local invasion along nerve bundles. Complete surgical resection is the mainstay of treatment. Adjuvant radiotherapy or chemotherapy does not confer a significant benefit, but may be added if complete resection is not possible. The 5-year survival rate is 53%, but drops to 16% in patients with neurofibromatosis or with large tumors (>5 cm).

Paraganglionic Tumors. Paraganglionic tumors arising in the thoracic cavity include chemodectomas and pheochromocytomas. Only 10% of all pheochromocytomas are located in an extraadrenal site. Intrathoracic pheochromocytomas are one of the most rare tumors. Approximately 10% of thoracic pheochromocytomas are malignant, a rate similar to that of adrenal tumors. The most common thoracic location is within the costovertebral sulcus, but paraganglionic tumors also arise within the visceral compartment of the mediastinum. These catecholamine-producing lesions can lead to life-threatening hemodynamic problems, so complete removal is important. Diagnosis is generally confirmed by measuring elevated levels of urinary catecholamines and their metabolites. Localization is by CT scan, aided by 131 I metaiodobenzylguanidine scintigraphy. Preoperative care includes alpha- and beta-adrenergic blockade to prevent intraoperative malignant hypertension and arrhythmias. These tumors tend to be highly vascular and should be approached with care. Chemodectomas are rare tumors that may be located around the aortic arch, vagus nerves, or aorticosympathetics. They rarely secrete catecholamines and are malignant in up to 30% of patients. Lymphoma Overall, lymphomas are the most common malignancy of the mediastinum. In about 50% of patients who have both Hodgkin’s and non-Hodgkin’s lymphoma, the mediastinum may be the primary site. The anterior compartment is most commonly involved, with occasional involvement of the middle compartment and hilar nodes.

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The posterior compartment is rarely involved Chemotherapy and/or radiation results in a cure rate of up to 90% for patients with earlystage Hodgkin’s disease, and up to 60% with more advanced stages.

Mediastinal Germ Cell Tumors Germ cell tumors are uncommon neoplasms, with only about 7000 diagnosed each year. However, they are the most common malignancy in young men between age 15 and 35 years. Most germ cell tumors are gonadal in origin. Those with the mediastinum as the primary site are rare, constituting less than 5% of all germ cell tumors, and less than 1% of all mediastinal tumors (usually occurring in the anterior compartment). If a malignant mediastinal germ cell tumor is found, it is important to exclude a gonadal primary tumor. Primary mediastinal germ cell tumors (including teratomas, seminomas, and nonseminomatous malignant germ cell tumors) are a heterogeneous group of benign and malignant neoplasms thought to originate from primitive pluripotent germ cells “misplaced” in the mediastinum during embryonic development. Previously, most mediastinal germ cell tumors were thought to be metastatic. However, two lines of evidence suggest that many mediastinal germ cell tumors are primary, developing from pluripotent primordial germ cells in the mediastinum: (1) several autopsy series showed that patients with extragonadal sites of germ cell tumors, presumed previously to have originated from the gonads, had no evidence of an occult primary tumor or of any residual scar of the gonads, even after an exhaustive search; and (2) patients treated by surgery or radiation for their mediastinal germ cell tumors had long-term survival with no late testicular recurrences. About one-third of all primary mediastinal germ cell tumors are seminomatous. Two-thirds are nonseminomatous tumors or teratomas. Treatment and prognosis vary considerably within these two groups. Mature teratomas are benign and can generally be diagnosed by the characteristic CT findings of multilocular cystic tumors, encapsulated with combinations of fluid, soft tissue, calcium, and/or fat attenuation in the anterior compartment. FNA biopsy alone may be diagnostic for seminomas, usually with normal serum markers, including hCG and AFP. In 10% of seminomas, hCG levels may be slightly elevated. FNA findings, along with high hCG and AFP levels, can accurately diagnose nonseminomatous tumors. If the diagnosis remains uncertain after assessment of FNA findings and serum marker levels, then core-needle biopsies or surgical biopsies may be required. An anterior mediastinotomy (Chamberlain procedure) or a thoracoscopy is the most frequent diagnostic surgical approach.

Teratoma. Teratomas are the most common type of mediastinal germ cell tumors, accounting for 60 to 70% of mediastinal germ cell tumors. They contain two or three embryonic layers that may include teeth, skin, hair (ectodermal), cartilage and bone (mesodermal), or bronchial, intestinal, or pancreatic tissue (endodermal). Therapy for mature, benign teratomas is surgical resection, which confers an excellent prognosis. Rarely, teratomas may contain a focus of carcinoma; these malignant teratomas (or teratocarcinomas) are locally aggressive. Often diagnosed at an unresectable stage, they respond poorly to chemotherapy and in a limited manner to radiotherapy; the prognosis is uniformly poor. Seminoma. Most patients with seminomas have advanced disease at the time of diagnosis and present with symptoms of local compression, including superior vena caval syndrome, dyspnea, or chest discomfort. With advanced disease, the preferred

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treatment is combination cisplatin-based chemotherapy regimens with bleomycin and either etoposide or vinblastine. Complete responses have been reported in over 75% of patients treated with these regimens. Surgical resection may be curative for small asymptomatic seminomas that are found incidentally with screening CT scans. Surgical resection of residual masses after chemotherapy may be indicated.

Nonseminomatous Germ Cell Tumors. Nonseminomatous germ cell tumors include embryonal cell carcinomas, choriocarcinomas, endodermal sinus tumors, and mixed types. They are often bulky, irregular tumors of the anterior mediastinum with areas of low attenuation on CT scan because of necrosis, hemorrhage, or cyst formation. Frequently, adjacent structures have been involved, with metastases to regional lymph nodes, pleura, and lungs. Lactate dehydrogenase (LDH), AFP, and hCG levels are frequently elevated. Chemotherapy is the preferred treatment and includes combination therapy with cisplatin, bleomycin, and etoposide. With this regimen, survival at 2 years is 67% and at 5 years is 60%. Surgical resection of residual masses is indicated, as it may guide further therapy. Up to 20% of residual masses contain additional tumors; in another 40%, mature teratomas; and the remaining 40%, fibrotic tissue. Mediastinal Cysts Primary Mediastinal Cyst Benign cysts account for up to 25% of mediastinal masses. Most are located in the middle compartment. Benign cysts are the most frequent mass in the middle mediastinal compartment. A CT scan showing characteristic features of near water density in a typical location is virtually 100% diagnostic.

Pericardial Cyst Pericardial cysts, the most common type of mediastinal cysts, are usually asymptomatic and detected incidentally. Typically they contain a clear fluid and appear in the right costophrenic angle. The cyst wall lining is a single layer of mesothelial cells. For most simple, asymptomatic pericardial cysts, observation alone is recommended. Surgical resection or aspiration may be indicated for complex cysts or large symptomatic cysts.

Bronchogenic Cyst Bronchogenic cysts are developmental anomalies that occur during embryogenesis and occur as an abnormal budding of the foregut or tracheobronchial tree. Most frequently they arise in the mediastinum, but about 15% occur within the pulmonary parenchyma. The most frequent mediastinal location is just posterior to the carina or main stem bronchus. Thin-walled and lined with respiratory epithelium, they contain a protein-rich mucoid material and varying amounts of seromucous glands, smooth muscle, and cartilage. They may communicate with the tracheobronchial tree. The management of bronchogenic cysts remains controversial. In children, most such cysts are symptomatic. Resection is generally recommended since serious complications may occur if the cyst becomes larger or infected. Complications include airway obstruction, infection, rupture, and rarely, malignant transformation. In adults, over half of all bronchogenic cysts are found incidentally during work-up for an unrelated problem or during screening. The natural history of an incidentally diagnosed, asymptomatic bronchogenic cyst is unknown, but it is clear that many such cysts do not lead to clinical problems. In one study of young military

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personnel, 78% of all bronchogenic cysts found on routine chest x-rays were asymptomatic. However, in other reports with more comprehensive follow-up, up to 67% of adults with incidentally found bronchogenic cysts eventually became symptomatic. Symptoms include chest pain, cough, dyspnea, and fever. Serious complications are less common and include hemodynamic compromise, airway obstruction, pulmonary artery obstruction, hemoptysis, and malignant degeneration. Symptomatic bronchogenic cysts should be removed. Traditionally, removal has been via posterolateral thoracotomy. Resection of infected cysts may be quite difficult because of dense adhesions; elective removal is often recommended before infection has a chance to occur. Thoracoscopic exploration and resection are possible for small cysts with minimal adhesions. The goal of minimally-invasive or open surgery should be complete removal of the cyst wall.

Enteric Cyst Most clinicians agree that in contrast to bronchogenic cysts, esophageal cysts should be removed, regardless of the presence or absence of symptoms. Esophageal cysts have a propensity for serious complications secondary to enlargement, leading to hemorrhage, infection, or perforation. Thus surgical resection is the treatment of choice in both adults and children.

Thymic Cyst Thymic cysts are generally asymptomatic and are discovered incidentally during radiographic work-up for an unrelated problem. Simple cysts are of no consequence; however, the occasional cystic neoplasm must be ruled out. Cystic components occasionally are seen in patients with thymoma and Hodgkin’s disease.

Ectopic Endocrine Glands Up to 5% of all mediastinal masses are estimated to be of thyroid origin. However, most of these masses are simple extensions of thyroid masses. They are usually nontoxic and over 95% of such masses can be completely resected through a cervical approach. True ectopic thyroid tissue of the mediastinum is rare. About 10 to 20% of abnormal parathyroid glands are found in the mediastinum; most can be removed during exploration from a cervical incision. In cases of true mediastinal parathyroid glands, thoracoscopic or open resection may be indicated. Location can generally be pinpointed by a combination of CT scan and Sestamibi scans.

Mediastinitis Acute Mediastinitis Acute mediastinitis is a fulminant infectious process that spreads along the fascial planes of the mediastinum. Infections originate most commonly from esophageal perforations, sternal infections, and oropharyngeal or neck infections, but a number of less common etiologic factors can lead to this deadly process (Table 18-17). As infections from any of these sources enter the mediastinum, spread may be rapid along the continuous fascial planes connecting the cervical and mediastinal compartments. Clinical signs and symptoms include fever, chest pain, dysphagia, respiratory distress, and cervical and upper thoracic subcutaneous crepitus. In severe cases, the clinical course can rapidly deteriorate to florid sepsis, hemodynamic instability, and death. Thus, a high index of suspicion is required in the context of any infection with access to the mediastinal compartments. A chest CT scan can be particularly helpful in determining the extent of spread and the best approach to surgical drainage. Acute

Table 18-17 Etiologic Factors in Acute Mediastinitis Esophageal Perforation Iatrogenic Balloon dilatation (for achalasia) Bougienage (for peptic stricture) Esophagoscopy Sclerotherapy (for variceal bleeding) Spontaneous Postemetic (Boerhaave’s syndrome) Straining during: Elimination Weight lifting Seizure Pregnancy Childbirth Ingestion of Foreign Bodies Trauma Blunt Penetrating Postsurgical Infection Anastomotic leak Erosion by cancer Deep sternotomy wound infection Oropharynx and neck infections Ludwig’s angina Quinsy Retropharyngeal abscess Cellulitis and suppurative lymphadenitis of neck Infections of lung and pleura Subphrenic abscess Rib or vertebral osteomyelitis Hematogenous or metastatic abscess source: Reproduced with permission from Razzuk MA et al: Infections of the mediastinum, in Pearson FG et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1604.

mediastinitis is a true surgical emergency and treatment must be instituted immediately and must be aimed at correcting the primary problem, such as the esophageal perforation or oropharyngeal abscess. Another major concern is d´ebridement and drainage of the spreading infectious process within the mediastinum, neck, pleura, and other tissue planes. Antibiotics, fluid resuscitation, and other supportive measures are important, but surgical correction of the problem at its source and open d´ebridement of infected areas are critical measures. Surgical d´ebridement may need to be repeated, and other planes and cavities explored depending on the patient’s clinical status. Blood cell counts and serial CT scans may also be required. Persistent sepsis or collections on CT scan may require further radical surgical d´ebridement.

Chronic Mediastinitis Sclerosing or fibrosing mediastinitis is a result of chronic inflammation of the mediastinum, most frequently as a result of granulomatous infections such as histoplasmosis or tuberculosis. The process begins in lymph nodes and continues as a chronic, low-grade inflammation leading to fibrosis and scarring. In many patients, the clinical manifestations are silent. However, if the fibrosis is progressive and severe, it may lead to encasement of the mediastinal structures, causing entrapment and compression of the low-pressure veins (including the superior vena cava and innominate and azygos veins). This fibrotic process can compromise other structures such as the esophagus and pulmonary arteries. There is no definitive treatment. Surgery is indicated only for diagnosis or in specific patients to relieve airway or esophageal obstruction or to achieve vascular

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reconstruction. Reports of palliative success with less invasive procedures (such as dilation and stenting of airways, the esophagus, or the superior vena cava) are promising. In one series of 22 patients, ketoconazole was effective in controlling progression. In another series of 71 patients, 30% died during long-term follow-up. Chronic mediastinitis is similar to the fibrotic changes that occur in other sites including retroperitoneal fibrosis, sclerosing cholangitis, and Riedel’s thyroiditis.

DISEASES OF THE PLEURA AND PLEURAL SPACE Anatomy The parietal pleura is a mesothelial lining of each hemithorax that invaginates at the hilum of each lung and continues on to cover each lung as the visceral pleura. Between these two surfaces is the potential pleural space, which is normally occupied only by a thin layer of lubricating pleural fluid. Two physiologic processes hold the visceral pleura of the lung in close apposition to the parietal pleura of the chest wall: those mechanisms that constantly remove pleural fluid and those that prevent an accumulation of free gas in the pleural space. A network of somatic, sympathetic, and parasympathetic fibers innervates the parietal pleura. Irritation of the parietal surface by inflammation, tumor invasion, trauma, and other processes can lead to a sensation of chest wall pain. The visceral pleura has no somatic innervation.

Pleural Effusion Pleural effusion refers to any significant collection of fluid within the pleural space. Normally, there is an ongoing balance between the lubricating fluid flowing into the pleural space and its continuous absorption. Between 5 and 10 L of fluid normally enters the pleural space daily by filtration through microvessels supplying the parietal pleura (located mainly in the less dependent regions of the cavity). The net balance of pressures in these capillaries leads to fluid flow from the parietal pleural surface into the pleural space, and the net balance of forces in the pulmonary circulation leads to absorption through the visceral pleura. Normally, 15 to 20 mL of pleural fluid is present at any given time. Any disturbance in these forces can lead to imbalance and accumulation of pleural fluid. Common pathologic conditions in North America that lead to pleural effusion include congestive heart failure, bacterial pneumonia, malignancy, and pulmonary emboli (Table 18-18).

Diagnostic Work-Up The initial diagnostic work-up for pleural effusion is guided in large part by the patient’s history and physical examination. Bilateral

pleural effusions are due to congestive heart failure in over 80% of patients. If the clinical history suggests this diagnosis, a trial of diuresis may be indicated (rather than thoracentesis). Up to 75% of effusions due to congestive heart failure resolve within 48 hours with diuresis alone. A patient presenting with cough, fever, leukocytosis, and unilateral infiltrate and effusion is likely to have a parapneumonic process. If the effusion is small and the patient responds to antibiotics, a diagnostic thoracentesis may be unnecessary. However, a patient who has an obvious pneumonia and a large pleural effusion that is purulent and foul-smelling has an empyema. Aggressive drainage with chest tubes is required, possibly with surgical intervention. Outside of the setting of congestive heart failure or small effusions associated with an improving pneumonia, most patients with pleural effusions of unknown cause should undergo thoracentesis. A general classification of pleural fluid collections into transudates and exudates is helpful in understanding the various causes (Table 18-19). Transudates are protein-poor ultrafiltrates of plasma that occur because of alterations in the systemic hydrostatic pressures or colloid osmotic pressures (for example, with congestive heart failure or cirrhosis). On gross visual inspection, a transudative effusion is generally clear or straw-colored. Exudates are proteinrich pleural fluid collections that generally occur because of inflammation or invasion of the pleura by tumors. Grossly, they are often turbid, bloody, or purulent. Grossly bloody effusions in the absence of trauma are frequently malignant, but may also occur in the setting of a pulmonary embolism or pneumonia. Several criteria have been traditionally used to differentiate transudates from exudates. An effusion is considered exudative if the pleural fluid to serum ratio of protein is greater than 0.5 and the LDH ratio is greater than 0.6 or the absolute pleural LDH level is greater than two-thirds of the normal upper limit for serum. If these criteria suggest a transudate, the patient should be carefully evaluated for congestive heart failure, cirrhosis, or conditions associated with transudates. If an exudative effusion is suggested, further diagnostic studies may be helpful. If total and differential cell counts reveal a predominance of neutrophils (>50% of cells), the effusion is likely to be associated with an acute inflammatory process (such as a parapneumonic effusion or empyema, pulmonary embolus, or pancreatitis). A predominance of mononuclear cells suggests a more chronic inflammatory process (such as cancer or tuberculosis). Gram’s stains and cultures should be obtained, if possible with inoculation into culture bottles at the bedside. Pleural fluid glucose levels are frequently decreased (500 mL per day in an adult, >100 mL in an infant) continues despite TPN and good lung expansion, early surgical ligation of the duct is recommended. Ligation can be approached best by right thoracotomy, and in some experienced centers, by right VATS. Chylothoraces due to malignant conditions often respond to radiation and/or chemotherapy, so less commonly require surgical ligation. Untreated chylothoraces are associated with significant nutritional and immunologic depletion that leads to significant mortality. Before the introduction of surgical ligation of the thoracic duct, the mortality rate from chylothorax exceeded 50%. With the availability of TPN for nutritional supplementation and surgical ligation for persistent leaks, the mortality rate of chylothorax is less than 10%.

Access and Drainage of Pleural Fluid Collections Approaches and Techniques Once the decision is made to invasively access a pleural effusion, the next step is to determine if a sample of the fluid is required or if complete drainage of the pleural space is desired. This step is influenced by the clinical history, the type and amount of fluid present, the nature of the collection (such as free-flowing or loculated), the cause, and the likelihood of recurrence. For small, free-flowing effusions, an outpatient thoracentesis with a relatively small–bore needle or catheter (14- to 16-gauge) can be performed (Fig. 18-42). This approach can be used for sampling fluid or for completely

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

THORACENTESIS

Confirm Diagnosis

Chest Tube

Conservative Management NPO Chest tube to suction Central hyperalimentation

Wait two weeks*

(Nonmalignant) Drainage persists (>500/d)

Drainage decrease (50 cc/d), early surgical ligation of the thoracic duct may be considered.

or pleurodesis, minimally-invasive surgery may be indicated, using a VATS approach.

Complications of Pleural Drainage The most common complication of invasive procedures to access the pleural space is inadvertent access to another cavity or organ. Examples include puncture of the underlying lung, with air leakage and pneumothorax; subdiaphragmatic entry, with damage to the liver, spleen, or other intra-abdominal viscera; bleeding secondary to intercostal vessel injury, or most commonly, larger vessel injury; and even cardiac puncture. Sometimes bleeding may be the result of an underlying coagulopathy or anticoagulant therapy. Other technical complications include loss of a catheter, guidewire, or fragment in the pleural space, and infections. Occasionally, rapid drainage of a large effusion can be followed by shortness of breath, clinical instability, and a phenomenon referred to as postexpansion pulmonary edema. For this reason, it is recommended to drain only up to 1 L

18/CHEST WALL, LUNG, MEDIASTINUM, AND PLEURA FIG. 18-42. Techniques for aspiration and drainage of a pleural effusion. A . Needle aspiration. With careful appraisal of the x-ray findings, the best interspace is selected, and fluid is aspirated with a needle and syringe. Large volumes of fluid can be removed with a little patience and a large-bore needle. B . Chest tube insertion. After careful skin preparation, draping, and administration of local anesthesia, a short skin incision is made over the correct interspace. The incision is deepened into the intercostal muscles, and the pleura is penetrated (usually with a clamp). When any doubt exists about the status of the pleural space at the site of puncture, the wound is enlarged bluntly to admit a finger, which can be swept around the immediately adjacent pleural space to assess the situation and break down any adhesions. The tube is inserted, with the tip directed toward the optimal position suggested by the chest x-rays. In general, a high anterior tube is best for air (pneumothorax) and a low posterior tube is best for fluid. A 28 to 32F tube is adequate for most situations. A 36F tube is preferred for hemothorax or for a viscous empyema. Many surgeons prefer a very small tube (16 to 20F) for drainage of simple pneumothorax. C . The tube is connected to a waterseal drainage system. Suction is added, if necessary, to expand the lung; it usually will be required in a patient with a substantial air leak (bronchopleural fistula).

605

B

A

initially. Most complications can be avoided by consulting with a clinician experienced in pleural drainage techniques.

Tumors of the Pleura Malignant Mesothelioma Malignant mesothelioma is the most common type of tumor of the pleura. The annual incidence in the United States is about 3000 cases. Other tumors of the pleura are much less common and include benign and malignant fibrous tumors of the pleura, lipomas, and cysts. In 20% of malignant mesotheliomas, the tumor arises from the peritoneum. Exposure to asbestos is the only known risk factor; it can be established in over 50% of patients. Geographic areas of increased incidence are frequently associated with industries using asbestos in the manufacturing process, such as shipbuilding. The risk extends beyond the worker directly exposed to the asbestos; family members exposed to the dust of the clothing or the work environment are also at risk. Other risk factors have been identified, including exposure to fibers with similar physical properties to amphibole and exposure to radiation. Cigarette smoking does not appear to increase the risk of malignant mesothelioma, even though asbestos exposure and smoking synergistically increases the risk for lung cancer. Malignant mesotheliomas have a male predominance of 2:1, and are most common after the age of 40.

Pathophysiology. The exact etiologic role of asbestos fibers has not been elucidated; however, the physical characteristics of specific fibers (referred to as serpentine or amphibole) have been shown to be important. The serpentine fibers are large and curly and are generally not able to travel beyond larger airways. However, the narrow, straight amphibole fibers, in particular the crocidolite

C

fibers, may navigate distally into the pulmonary parenchyma and are most clearly associated with mesotheliomas. The latency period between asbestos exposure and the development of mesothelioma is at least 20 years. The tumor generally is multicentric, with multiple pleural-based nodules coalescing to form sheets of tumor. This process initially involves the parietal pleura, generally with early spread to the visceral surfaces and with a variable degree of invasion of surrounding structures. Autopsy studies have shown that most patients have distant metastases, but the natural history of the disease in untreated patients culminates in death due to local extension.

Clinical Presentation. Most patients present with dyspnea and chest pain. Over 90% have a pleural effusion. Thoracentesis is diagnostic in less than 10% of patients. Frequently, a thoracoscopy or open pleural biopsy with special stains is required to differentiate mesotheliomas from adenocarcinomas (Table 18-25). Once the diagnosis is confirmed, cell types can be distinguished (e.g., epithelial, Table 18-25 Special Stains Required to Differentiate Mesothelioma from Adenocarcinoma

CEA Vimentin LMW cytokeratins EM features

Mesothelioma

Adenocarcinoma

Negative

Positive

Positive Long, sinuous villi

Negative Short, straight villi, with fuzzy glycocalyx

CEA = carcinoembryonic antigen; EM = electron microscope; LMW = low molecular weight.

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sarcomatous, and mixed). Epithelial types are associated with a more favorable prognosis, and in some patients long-term survival may be seen with no treatment. Sarcomatous and mixed tumors share a more aggressive course.

Management. The treatment of malignant mesotheliomas remains controversial. It has been the subject of a number of recent clinical trials, the vast majority with limited success. A new staging system has been devised that has clearly shown prognostic value (Table 18-26). However, while prognosis does depend on the stage of the disease, the problem is that many patients present with advanced local or distant disease beyond curative potential. Treatment options include supportive care only, surgical resection, and multimodality approaches (using a combination of surgery, chemotherapy, and radiation therapy). Surgical options include palliative approaches such as pleurectomy or talc pleurodesis. Palliative approaches may lead to local

control and a modest improvement in short-term survival. More radical surgical approaches (such as extrapleural pneumonectomy followed by adjuvant chemotherapy and radiation) have an increased morbidity rate; moreover, the mortality rate exceeds 10% in all but the most experienced centers. In one Japanese review, extrapleural pneumonectomy demonstrated no improvement in survival (as compared with debulking surgery), and showed no benefit over adjuvant therapy: the overall 5-year survival in all groups was less than 10%. However, several reports of trials of radical surgery combined with multimodality adjuvant therapy have shown reasonable improvements in survival for patients with early-stage tumors (as compared with historical controls). In one series of 183 patients undergoing extrapleural pneumonectomy and adjuvant chemotherapy and radiation, a subset of 31 patients had favorable prognostic features (i.e., epithelial cell type), negative resection margins, and negative extrapleural node status. This favorable subset had a 5-year survival rate of 46%, as compared with 15% for the entire group.

Table 18-26 International Mesothelioma Interest Group Staging System for Diffuse Malignant Pleural Mesothelioma T Tumor T1

T1a Tumor limited to the ipsilateral parietal ± mediastinal ± diaphragmatic pleura No involvement of the visceral pleura T1b Tumor involving the ipsilateral parietal ± mediastinal ± diaphragmatic pleura Tumor also involving the visceral pleura T2 Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleurae) with at least one of the following features: Involvement of diaphragmatic muscle Extension of tumor from visceral pleura into the underlying pulmonary parenchyma T3 Describes locally advanced but potentially resectable tumor Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleurae) with at least one of the following features: Involvement of the endothoracic fascia Extension into the mediastinal fat Solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall Nontransmural involvement of the pericardium T4 Describes locally advanced technically unresectable tumor Tumor involving all of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleurae) wilh at least one of the following features: Diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction Direct transdiaphragmatic extension of tumor to the peritoneum Direct extension of tumor to the contralateral pleura Direct extension of tumor to mediastinal organs Direct extension of tumor into the spine Tumor extending through to the internal surface of the pericardium with or without a pericardial effusion; or tumor involving the myocardium N Lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases Nl Metastases in the ipsilateral bronchopulmonary or hilar lymph nodes N2 Metastases in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral internal mammary nodes N3 Metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes M Metastases MX Presence of distant metastases cannot be assessed M0 No distant metastases M1 Distant metastases present Staging Stage I Ia T1a N0 M0 Ib T1b N0 M0 Stage II T2 N0 M0 Stage III Any T3 Any N1 M0 Any N2 Stage IV Any T4 Any N3 Any M1 source: Reproduced with permission from International Mesothelioma Interest Group: A proposed new international TNM staging system for malignant pleural mesothelioma. Chest 108:1122, 1995.

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In another series, 88 patients with mesotheliomas were studied prospectively. Adjuvant radiation therapy was given to 54 patients after extrapleural pneumonectomy; the median survival was 17 months. However, in patients with stage I and II disease, the median survival was significantly better at 33.0 months. The authors’ current approach to malignant mesotheliomas is based on tumor stage and pulmonary performance status. For patients with early-stage mesotheliomas and good pulmonary function, extrapleural pneumonectomy is recommended, especially for epithelial mesotheliomas. Patients are referred for clinical trials of multimodality therapy, if available. For more advanced disease, or if patients have less-than-optimal pulmonary function or performance status, talc pleurodesis or supportive therapy is recommended. Intrapleural therapy has been explored to improve the locoregional control of malignant mesotheliomas. In a phase II trial, 37 patients underwent pleurectomy with decortication, followed by intrapleural and systemic therapy with cisplatin and mitomycin C. Their median survival was 17 months, with a locoregional recurrence rate of 80%. According to another study, the addition of hyperthermic intrapleural perfusion seems to be pharmacokinetically advantageous; of seven patients, three underwent pleurectomy with decortication and received hyperthermic cisplatin. Systemic drug concentrations were greater after pleurectomy with decortication than after pleuropneumonectomy. The local tissue:perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. Another promising alternative to enhance the local efficacy of chemotherapy against malignant mesotheliomas is L-NDDP (cisbis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum), a new lipophilic cisplatinum analogue produced by the University of Texas M. D. Anderson Cancer Center in Houston, Texas. A phase II trial of L-NDDP enrolled 23 patients to receive a thoracoscopic biopsy and a cytologic examination before and after treatment. Of those 23 patients, 13 (56%) had a complete pathologic response; of the patients with positive cytologic results, 15 (83%) had a complete cytologic response. The findings of this phase II trial led to an ongoing phase II clinical trial at the University of Pittsburgh Cancer Institute to investigate intrapleural L-NDDP followed by surgical dissection and postoperative radiotherapy in patients with malignant mesotheliomas.

Fibrous Tumors of the Pleura Fibrous tumors of the pleura are unrelated to asbestos exposure or malignant mesotheliomas. They generally occur as a single pedunculated mass arising from the visceral pleura. Frequently, they are discovered incidentally on routine chest x-rays, without an associated pleural effusion. Fibrous tumors of the pleura may be benign or malignant. Symptoms such as cough, chest pain, and dyspnea occur in 30 to 40% of patients. Less common are fever, hypertrophic pulmonary osteoarthropathy, hemoptysis, and hypoglycemia. Hypoglycemia occurs in only approximately 4% of patients and resolves with surgical resection, as do the other symptoms. Given the localized, pedunculated nature of both benign and malignant fibrous tumors of the pleura, most are cured by complete surgical resection. Incompletely resected malignant tumors may recur locally or metastasize; frequently, they are fatal within 2 to 5 years.

Acknowledgement The authors wish to thank Chuong D. Hoang, MD, Denis R. Clohisy, MD, Mary Knatterud, PhD, Vita Sullivan, MD, and Jennifer Nichols

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18/CHEST WALL, LUNG, MEDIASTINUM, AND PLEURA Mansour KA, Thourani VH, Losken A, et al: Chest wall resections and reconstruction: A 25-year experience. Ann Thorac Surg 73:1720, 2002. Somers J, Faber LP: Chondroma and chondrosarcoma. Semin Thorac Cardiovasc Surg 11:270, 1999. Walsh GL, Davis BM, Swisher SG, et al: A single-institutional, multidisciplinary approach to primary sarcomas involving the chest wall requiring full-thickness resections. J Thorac Cardiovasc Surg 121:48, 2001. Mediastinum: General Concepts Kirschner PA: Anatomy and surgical access of the mediastinum, in Pearson FG, Cooper JD, Deslauriers J, et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1563. Mediastinum: Diagnostic Evaluation Baron RL, Levitt RG, et al: Computed tomography in the evaluation of mediastinal widening. Radiology 138:107, 1981. Fraser RS, Pare PD, Bralow L, et al: Diagnosis of Diseases of the Chest, 4th ed, Vol. 1–4. Philadelphia: WB Saunders, 1999. Mediastinum: Neoplasms Blossom GB, Steiger Z, Stephenson LWL: Neoplasms of the mediastinum, in DeVita VT, Hellman S, Rosenberg SA (eds): Cancer—Principles and Practice of Oncology, 5th ed. Philadelphia: Lippincott-Raven, 1997, p 951. Blumberg D, Port JL, Weksler B, et al: Thymoma: A multivariate analysis of factors predicting survival. Ann Thorac Surg 60:908, 1995. Bousamra M: Neurogenic tumors of the mediastinum, in Pearson FG, Cooper JD, Deslauriers J, et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1732. Bukowski RM, Wolf M, Kulander BG, et al: Alternating combination chemotherapy in patients with extragonadal germ cell tumors. Cancer 71:2631, 1993. Chahanian A: Chemotherapy of thymomas and thymic carcinomas. Chest Surg Clin North Am 11:447, 2001. Coleman BG, Arger PH, Dalinka MK: CT of sarcomatous degeneration in neurofibromatosis. AJR 140:383, 1983. Davidson KG, Walbaum PR, McCormack RJ: Intrathoracic neural tumours. Thorax 33:359, 1978. Deslauriers J, Letourneau L, Giubilei G: Diagnostic strategies in mediastinal tumors and masses, in Pearson FG, Cooper JD, Deslauriers J, et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1655. Ducatman BS, Scheithauer BW, Peipgras DG: Malignant peripheral nerve sheath tumours: A clinicopathologic study of 120 cases. Cancer 57:2006, 1986. Gale AW, Jelihovsky T, Grant AF: Neurogenic tumors of the mediastinum. Ann Thorac Surg 17:434, 1974. Gunther RW: Percutaneous interventions in the thorax. Seventh Annual Charles Dotter Memorial Lecture. J Vasc Intervent Radiol 3:379, 1992. Herman SJ, Holub RV, Weisbrod GL, et al: Anterior mediastinal masses: Utility of transthoracic needle biopsy. Radiology 180:167, 1991. Hoerbelt R, Keunecke L, Grimm H, et al: The value of a noninvasive diagnostic approach to mediastinal masses. Ann Thorac Surg 75:1086, 2003. Knapp RH, Hurt RD, Payne WS, et al: Malignant germ cell tumors of the mediastinum. J Thorac Cardiovasc Surg 89:82, 1985. Larsen SS, Krasnik M, Vilmann P, et al: Endoscopic ultrasound-guided biopsy of mediastinal lesions has a major impact on patient management. Thorax 57:98, 2002. Luketich JD, Ginsberg RJ: Current management of patients with mediastinal tumors. Adv Surg 30:311, 1996. Luketich JD, Friedman DM, Weigel TL, et al: Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans. Ann Thorac Surg 68:1133, 1999. Masaoka A, Monden Y, Nakahara K, et al: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48:2485, 1981. Meyers BF, Cooper JD: Transcervical thymectomy for myasthenia gravis. Chest Surg Clin North Am 11:363, 2001.

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Chylothorax Malthaner RA, Inculet RI: The thoracic duct and chylothorax, in Pearson FG, Cooper JD, Deslauriers J, et al (eds): Thoracic Surgery, 2nd ed. New York: Churchill Livingstone, 2002, p 1228. Miller JI Jr.: Diagnosis and management of chylothorax. Chest Surg Clin North Am 6:139, 1996. Access and Drainage of Pleural Fluid Collections Gammie JS, Banks MC, Fuhrman CR, et al: The pigtail catheter for pleural drainage: A less invasive alternative to tube thoracostomy. JSLS 3:57, 1999. Luketich JD, Kiss M, Hershey J, et al: Chest tube insertion: A prospective evaluation of pain management. Clin J Pain 14:152, 1998. Tumors of the Pleura Cole FH Jr., Ellis RA, Goodman RC, et al: Benign fibrous pleural tumor with elevation of insulin-like growth factor and hypoglycemia. South Med J 83:690, 1990. England DM, Hochholzer L, McCarthy MJ: Localized benign and malignant fibrous tumors of the pleura: A clinicopathologic review of 223 cases. Am J Pathol 13:647, 1989.

Khalil MY, Mapa M, Shin HJ, et al: Advances in the management of malignant mesothelioma. Curr Oncol Rep 5:334, 2003. Ratto GB, Civalleri D, Esposito M, et al: Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: A feasibility and pharmacokinetic study. J Thorac Cardiovasc Surg 117:759, 1999. Rusch V, Saltz L, Venkatraman E, et al: A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma. J Clin Oncol 12:1156, 1994. Rusch VW: The international mesothelioma interest group: A proposed new international staging system for malignant pleural mesothelioma. Chest 108:122, 1995. Rusch VW, Rosenzweig K, Venkatraman E, et al: A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 122:788, 2001. Sugarbaker DJ, Flores RM, Jaklitsch MT, et al: Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients. J Thorac Cardiovasc Surg 117:54, 1999. Takagi K, Tsuchiya R, Watanabe Y: Surgical approach to pleural diffuse mesothelioma in Japan. Lung Cancer 31:57, 2001.

CHAPTER

19

Congenital Heart Disease Tara B. Karamlou, Irving Shen, and Ross M. Ungerleider

Defects Where Repair is the Only or Best Option Atrial Septal Defect Embryology Anatomy Pathophysiology Diagnosis Treatment Results Aortic Stenosis Anatomy and Classification Pathophysiology Diagnosis Treatment Patent Ductus Arteriosus Anatomy Natural History Clinical Manifestations and Diagnosis Therapy Outcomes Aortic Coarctation Anatomy Pathophysiology Diagnosis Therapy Truncus Arteriosus Anatomy Physiology and Diagnosis Repair Results Total Anomalous Pulmonary Venous Connection Anatomy and Embryology Pathophysiology and Diagnosis Therapy Results Cor Triatriatum Anatomy Pathophysiology and Diagnosis Therapy Aortopulmonary Window Embryology and Anatomy Pathophysiology and Diagnosis Therapy Results Defects Requiring Palliation Tricuspid Atresia Anatomy Pathophysiology

Diagnosis Treatment Results Hypoplastic Left-Heart Syndrome Anatomy Pathophysiology and Diagnosis Treatment Results Defects That May Be Palliated or Repaired Ebstein’s Anomaly Anatomy Pathophysiology Diagnosis Treatment Results Transposition of the Great Arteries Anatomy Pathophysiology Clinical Manifestations and Diagnosis Surgical Repair Results Double-Outlet Right Ventricle Anatomy Clinical Manifestations and Diagnosis Therapy Results Tetralogy of Fallot Anatomy Pathophysiology and Clinical Presentation Treatment Results Ventricular Septal Defect Anatomy Pathophysiology and Clinical Presentation Diagnosis Treatment Results Atrioventricular Canal Defects Anatomy Pathophysiology and Diagnosis Treatment Results Interrupted Aortic Arch Anatomy Clinical Manifestations and Diagnosis Treatment Results

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Congenital heart surgery is a constantly evolving field. The last 20 years have brought about rapid developments in the technologic realm as well as a more thorough understanding of both the anatomy and pathophysiology of congenital heart disease, leading to the improved care of patients with this challenging disease.1,2 These new advancements created a paradigm shift in the field of pediatric heart surgery. The traditional strategy of initial palliation followed by definitive correction at a later age, which had pervaded the thinking of most surgeons, began to evolve to one emphasizing early repair, even in the tiniest patients.2 Furthermore, some of the defects that were virtually uniformly fatal (such as hypoplastic left-heart syndrome) now can be successfully treated with aggressive forms of palliation using cardiopulmonary bypass, resulting in outstanding survival for many of these children. Because the goal in most cases of congenital heart disease (CHD) is now early repair, as opposed to subdividing lesions into cyanotic or noncyanotic lesions, a more appropriate classification scheme divides particular defects into three categories based on the feasibility of achieving this goal: (1) defects that have no reasonable palliation and for which repair is the only option; (2) defects for which repair is not possible and for which palliation is the only option; and (3) defects that can either be repaired or palliated in infancy.3 It bears mentioning that all defects in the second category are those in which the appropriate anatomic components either are not present, as in hypoplastic left-heart syndrome, or cannot be created from existing structures.

DEFECTS WHERE REPAIR IS THE ONLY OR BEST OPTION

A B

C FIG. 19-1. The anatomy of atrial septal defects. In the sinus venosus type ( A ), the right upper and middle pulmonary veins frequently drain to the superior vena cava or right atrium. B . Secundum defects generally occur as isolated lesions. C . Primum defects are part of a more complex lesion and are best considered as incomplete atrioventricular septal defects. (Reproduced with permission from Mosca et al,4 p 1444.)

Atrial Septal Defect

Pathophysiology

An atrial septal defect (ASD) is defined as an opening in the interatrial septum that enables the mixing of blood from the systemic venous and pulmonary venous circulations.

ASDs result in an increase in pulmonary blood flow secondary to left-to-right shunting through the defect. The direction of the intracardiac shunt is predominantly determined by the compliance of the respective ventricles. In utero, the distensibility, or compliance, of the right and left ventricles is equal, but postnatally the left ventricle (LV) becomes less compliant than the right ventricle (RV). This shift occurs because the resistance of the downstream vascular beds changes after birth. The pulmonary vascular resistance falls with the infant’s first breath, decreasing RV pressure, whereas the systemic vascular resistance rises dramatically, increasing LV pressure. The increased LV pressure creates a thicker muscle mass, which offers a greater resistance to diastolic filling than does the RV; thus, the majority of flow through the ASD occurs from left to right. The greater volume of blood returning to the right atrium causes volume overload in the RV, but because of its lower muscle mass and low-resistance output, it easily distends to accommodate this load.5,6 The long-term consequences of RV volume overload include hypertrophy with elevated RV end-diastolic pressure and a relative pulmonary stenosis across the pulmonary valve, because it cannot accommodate the increased RV flow. The resistance at the level of the pulmonary valve then contributes a further pressure load on the RV, which accelerates RV hypertrophy. Compliance gradually decreases as the right ventricular pressure approaches systemic pressure, and the size of the left-to-right shunt decreases. Patients at this stage have a balanced circulation and may deceptively appear less symptomatic. A minority of patients with ASDs develop progressive pulmonary vascular changes as a result of chronic overcirculation. The increased pulmonary vascular resistance in these patients leads to an equalization of left and right ventricular pressures, and their ratio of

Embryology The atrial and ventricular septa form between the third and sixth weeks of fetal development. After the paired heart tubes fuse into a single tube folded onto itself, the distal portion of the tube causes an indentation to form in the roof of the common atrium. Near this portion of the roof, the septum primum arises and extends into a crescentic formation toward the atrioventricular (AV) junction. The gap remaining between the septum primum and the developing tissues of the AV junction is called the ostium primum. Before the septum primum fuses completely with the endocardial cushions, a series of fenestrations appear in the septum primum that coalesce into the ostium secundum. During this coalescence, the septum secundum grows downward from the roof of the atrium, parallel to and to the right of the septum primum. The septum primum does not fuse, but creates an oblique pathway, called the foramen ovale, within the interatrial septum. After birth, the increase in left atrial pressure normally closes this pathway, obliterating the interatrial connection.4

Anatomy ASDs can be classified into three different types: (1) sinus venosus defects, comprising approximately 5 to 10% of all ASDs; (2) ostium primum defects, which are more correctly described as partial atrioventricular canal defects; and (3) ostium secundum defects, which are the most prevalent subtype, comprising 80% of all ASDs (Fig. 19-1).5

19/CONGENITAL HEART DISEASE

pulmonary (Qp) to systemic flow (Qs), Qp:Qs, will approach 1.5,7 This does not mean, however, that there is no intracardiac shunting, only that the ratio between the left-to-right component and the rightto-left component is equal. The ability of the right ventricle to recover normal function is related to the duration of chronic overload, because those undergoing ASD closure before age 10 years have a better likelihood of achieving normal RV function in the postoperative period.3 The physiology of sinus venosus ASDs is similar to that discussed above except that these are frequently accompanied by anomalous pulmonary venous drainage. This often results in significant hemodynamic derangements that accelerate the clinical course of these infants. The same increase in symptoms is true for those with ostium primum defects because the associated mitral insufficiency from the “cleft” mitral valve can lead to more atrial volume load and increased atrial level shunting.

Diagnosis Patients with ASDs may present with few physical findings. Auscultation may reveal prominence of the first heart sound with fixed splitting of the second heart sound. This results from the relatively fixed left-to-right shunt throughout all phases of the cardiac cycle. A diastolic flow murmur indicating increased flow across the tricuspid valve may be discerned, and, frequently, an ejection flow murmur can be heard across the pulmonary valve. A right ventricular heave and increased intensity of the pulmonary component of the second heart sound indicates pulmonary hypertension and possible unrepairability. Chest radiographs in the patient with an ASD may show evidence of increased pulmonary vascularity, with prominent hilar markings and cardiomegaly. The electrocardiogram shows right axis deviation with an incomplete bundle-branch block. When right bundle-branch block is associated with a leftward or superior axis, an AV canal defect should be strongly suspected.8 Diagnosis is clarified by two-dimensional echocardiography, and use of color-flow mapping facilitates an understanding of the physiologic derangements created by the defects.9 Echocardiography also enables the clinician to estimate the amount of intracardiac shunting, can demonstrate the degree of mitral regurgitation in patients with ostium primum defects, and with the addition of microcavitation, can assist in the detection of sinus venosus defects.5 The advent of two-dimensional echocardiography with colorflow Doppler has largely obviated the need for cardiac catheterization because the exact nature of the ASD can be precisely defined by echo alone. However, in cases where the patient is older than age 40 years, catheterization can quantify the degree of pulmonary hypertension present, because those with a pulmonary vascular resistance (PVR) greater than 12 U/mL are considered inoperable.10 Cardiac catheterization also can be useful in that it provides data that enable the calculation of Qp and Qs so that the magnitude of the intracardiac shunt can be determined. The ratio (Qp:Qs) can then be used to determine whether closure is indicated in equivocal cases, because a Qp:Qs greater than 1.5:1 is generally accepted as the threshold for surgical intervention. Finally, in patients older than age 40 years, cardiac catheterization can be important to disclose the presence of coronary artery disease. In general, ASDs are closed when patients are between 4 and 5 years of age. Children of this size can usually be operated on without the use of blood transfusion and generally have excellent outcomes. Patients who are symptomatic may require repair earlier, even in infancy. Some surgeons, however, advocate routine repair in

613

infants and children, as even smaller defects are associated with the risk of paradoxical embolism, particularly during pregnancy. In a recent review by Reddy and colleagues, 116 neonates weighing less than 2500 g who underwent repair of simple and complex cardiac defects with the use of cardiopulmonary bypass were found to have no intracerebral hemorrhages, no long-term neurologic sequelae, and a low operative-mortality rate (10%). These results correlated with the length of cardiopulmonary bypass and the complexity of repair.11 These investigators also found an 80% actuarial survival at 1 year and, more importantly, that growth following complete repair was equivalent to weight-matched neonates free from cardiac defects.11

Treatment ASDs can be repaired in a facile manner using standard cardiopulmonary bypass (CPB) techniques through a midline sternotomy approach.7 The details of the repair itself are generally straightforward. An oblique atriotomy is made, the position of the coronary sinus and all systemic and pulmonary veins are determined, and the rim of the defect is completely visualized. Closure of ostium secundum defects is accomplished either by direct suture or by insertion of a patch. The decision of whether patch closure is necessary can be determined by the size and shape of the defect as well as by the quality of the edges. Sinus venosus ASDs associated with partial anomalous pulmonary venous connection are repaired by inserting a patch, with redirection of the pulmonary veins behind the patch to the left atrium. Care must be taken with this approach to avoid obstruction of the pulmonary veins or the superior vena cava, although usually the superior vena cava is dilated and provides ample room for patch insertion. These operative strategies have been well established, with a low complication rate and a mortality rate approaching zero. As such, attention has shifted to improving the cosmetic result and minimizing hospital stay and convalescence. Multiple new strategies have been described to achieve these aims, including the right submammary incision with anterior thoracotomy, limited bilateral submammary incision with partial sternal split, transxiphoid window, and limited midline incision with partial sternal split.4,12–14 Some centers use video-assisted thoracic surgery (VATS) in the submammary and transxiphoid approaches to facilitate closure within a constricted operative field. The morbidity and mortality of all of these approaches are comparable to those of the traditional median sternotomy; however, each has technical drawbacks. The main concern is that operative precision be maintained with limited exposure. Luo and associates recently described a prospective randomized study comparing ministernotomy (division of the upper sternum for aortic and pulmonary lesions, and the lower sternum for septal lesions) to full sternotomy in 100 consecutive patients undergoing repair of septal lesions.14 The patients in the ministernotomy group had longer procedure times (by 15 to 20 minutes), less bleeding, and shorter hospital stays. These results have been echoed by other investigators from Boston who maintain that ministernotomy provides a cosmetically acceptable scar without compromising aortic cannulation or limiting the exposure of crucial mediastinal structures.12 This approach also can be easily extended to a full sternotomy should difficulty or unexpected anomalies be encountered.13 First performed in 1976, transcatheter closure of ASDs with the use of various occlusion devices is gaining widespread acceptance.15 Certain types of ASDs, including patent foramen ovale, secundum defects, and some fenestrated secundum defects, are amenable to device closure. Complications reported to occur

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

with transcatheter closure include air embolism (1 to 3%); thromboembolism from the device (1 to 2%); disturbed atrioventricular valve function (1 to 2%); systemic/pulmonary venous obstruction (1%); perforation of the atrium or aorta with hemopericardium (1 to 2%); atrial arrhythmias (1 to 3%); and malpositioning/ embolization of the device requiring intervention (2 to 15%).4,16 Thus, although percutaneous approaches are cosmetic and often translate into shorter periods of convalescence, their attendant risks are considerable, especially because their use may not result in complete closure of the septal defect.

Results Surgical repair of ASDs should be associated with a mortality rate near zero.4,5,7,8,11 Early repairs in neonates weighing less than 1000 g have been increasingly reported with excellent results.11 Uncommonly, atrial arrhythmias or significant left atrial hypertension may occur soon after repair. The latter is caused by the noncompliant small, left atrial chamber and generally resolves rapidly.

Aortic Stenosis Anatomy and Classification The spectrum of aortic valve abnormality represents the most common form of CHD, with the great majority of patients being asymptomatic until midlife. Obstruction of the left ventricular outflow tract (LVOT) occurs at multiple levels: subvalvular, valvular, and supravalvular (Fig. 19-2). The critically stenotic aortic valve in the neonate or infant is commonly unicommissural or bicommissural, with thickened, dysmorphic, and myxomatous leaflet tissue and a reduced cross-sectional area at the valve level. Associated left-

sided lesions are often present. In a review of 32 cases from the Children’s Hospital in Boston, 59% had unicommissural valves and 40% had bicommissural valves.17 Associated lesions were frequent, occurring in 88% of patients, most commonly patent ductus arteriosus, mitral regurgitation, and hypoplastic left ventricle. Endocardial fibroelastosis also is common among infants with critical aortic stenosis (AS).18 In this condition, the LV is largely nonfunctional, and these patients are not candidates for simple valve replacement or repair, because the LV is incapable of supporting the systemic circulation. Often, the LV is markedly hypertrophic with a reduced cavity size, but on rare occasion, a dilated LV, reminiscent of overt heart failure, is encountered.19

Pathophysiology The unique intracardiac and extracardiac shunts present in fetal life allow even neonates with critical AS to survive. In utero, left ventricular hypertrophy and ischemia cause left atrial hypertension, which reduces the right-to-left flow across the foramen ovale. In severe cases, a reversal of flow may occur, causing right ventricular volume loading. The RV then provides the entire systemic output via the patent ductus arteriosus. Although cardiac output is maintained, the LV suffers continued damage as the intracavitary pressure precludes adequate coronary perfusion, resulting in LV infarction and subendocardial fibroelastosis. The presentation of the neonate with critical AS is then determined by both the degree of left ventricular dysfunction and on the completeness of the transition from a parallel circulation to an in-series circulation (i.e., on closure of the foramen ovale and the ductus arteriosus). Those infants with mildto-moderate AS in which LV function is preserved are asymptomatic at birth. The only abnormalities may be a systolic ejection murmur and electrocardiogram (ECG) evidence of left ventricular hypertrophy. However, those neonates with severe AS and compromised LV function are unable to provide adequate cardiac output at birth, and will present in circulatory collapse once the ductus closes, with dyspnea, tachypnea, irritability, narrowed pulse pressure, oliguria, and profound metabolic acidosis.7,20 If ductal patency is maintained, systemic perfusion will be provided by the RV via ductal flow, and cyanosis may be the only finding.

Diagnosis

A

B

C

D

FIG. 19-2. The anatomy of the types of congenital aortic stenosis. A . Valvular aortic stenosis. B . Supravalvular aortic stenosis and its repair (insert). C. Tunnel-type subvalvular aortic stenosis. D . Membranous subvalvular aortic stenosis. (Reproduced with permission from Mosca et al,4 p 1247.)

Neonates and infants with severe valvular AS may have a relatively nonspecific history of irritability and failure to thrive. Angina, if present, is usually manifested by episodic, inconsolable crying that coincides with feeding. As discussed previously, evidence of poor peripheral perfusion, such as extreme pallor, indicates severe LVOT obstruction. Differential cyanosis is an uncommon finding, but is present when enough antegrade flow occurs only to maintain normal upper body perfusion, while a large patent ductus arteriosus produces blue discoloration of the abdomen and legs. Physical findings include a systolic ejection murmur, although a quiet murmur may paradoxically indicate a more severe condition with reduced cardiac output. A systolic click correlates with a valvular etiology of obstruction. As LV dysfunction progresses, evidence of congestive heart failure occurs. The chest radiograph is variable, but may show dilatation of the aortic root, and the ECG often demonstrates LV hypertrophy. Echocardiography with Doppler flow is extremely useful in establishing the diagnosis, as well as quantifying the transvalvular gradient.21 Furthermore, echocardiography can facilitate evaluation for the several associated defects that can be present in critical neonatal AS, including mitral stenosis, LV hypoplasia, LV endocardial

19/CONGENITAL HEART DISEASE

fibroelastosis, subaortic stenosis, VSD, or coarctation. The presence of any or several of these defects has important implications related to treatment options for these patients. Although cardiac catheterization is not routinely performed for diagnostic purposes, it can be invaluable as part of the treatment algorithm if the lesion is amenable to balloon valvotomy.

615

Ascending aorta incised Right coronary artery

Treatment The infant with severe AS may require urgent intervention. Preoperative stabilization, however, has dramatically altered the clinical algorithm and outcomes for this patient population.18,20 The preoperative strategy begins with endotracheal intubation and inotropic support. Prostaglandin infusion is initiated to maintain ductal patency, and confirmatory studies are performed prior to operative intervention. Therapy is generally indicated in the presence of a transvalvular gradient of 50 mm Hg with associated symptoms including syncope, CHF, or angina, or if a gradient of 50 to 75 mm Hg exists with concomitant ECG evidence of LV strain or ischemia. In the critically ill neonate, there may be little gradient across the aortic valve because of poor LV function. These patients depend on patency of the ductus arteriosus to provide systemic perfusion from the RV, and all ductal-dependent patients with critical AS require treatment. However, the decision regarding treatment options must be based on a complete understanding of associated defects. For example, in the presence of a hypoplastic LV (left ventricular enddiastolic volume 3 cm in diameter), air–fluid levels seen on upright films, and a paucity of air in the colon. The sensitivity of abdominal radiographs in the detection of small-bowel obstruction ranges from 70 to 80%.25,26 Specificity is low, because ileus and colonic obstruction can be associated with findings that mimic those observed with small-bowel obstruction. False-negative findings on radiographs can result when the site of obstruction is located in the proximal small bowel and when the bowel lumen is filled with fluid but no gas, thereby preventing visualization of air– fluid levels or bowel distention. The latter situation is associated with closed-loop obstruction. Despite these limitations, abdominal radiographs remain an important study in patients with suspected smallbowel obstruction because of their widespread availability and low cost. Computed tomographic (CT) scanning is 80 to 90% sensitive and 70 to 90% specific in the detection of small-bowel obstruction.25,26 The findings of small-bowel obstruction include a discrete transition zone with dilation of bowel proximally, decompression of bowel distally, intraluminal contrast that does not pass beyond the transition zone, and a colon containing little gas or fluid. CT scanning may also provide evidence for the presence of closed-loop obstruction and strangulation (Fig. 27-16). Closed-loop obstruction is suggested by the presence of a U-shaped or C-shaped dilated bowel loop as-

FIG. 27-16. Small-bowel obstruction with strangulation. This CT scan of a patient with strangulating small-bowel obstruction shows dilated small-bowel loops with extensive pneumatosis intestinalis.

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sociated with a radial distribution of mesenteric vessels converging toward a torsion point. Strangulation is suggested by thickening of the bowel wall, pneumatosis intestinalis (air in the bowel wall), portal venous gas, mesenteric haziness, and poor uptake of intravenous contrast into the wall of the affected bowel. CT scanning also offers a global evaluation of the abdomen and may therefore reveal the etiology of obstruction. This feature also is important in the acute setting when intestinal obstruction represents only one of many diagnoses in patients presenting with acute abdominal conditions. A limitation of CT scanning is its low sensitivity (3 6.5) and Creatinine >300 µmol/L (>3.4 mg/dL) in patients with grade 3 or 4 encephalopathy 2. Viral hepatitis/drug reaction (non-acetaminophen causes) a. Prothrombin time >100 seconds (INR >6.5 regardless of grade of encephalopathy) or Any 3 of the following (regardless of grade of encephalopathy) b. Age 40 years c. Duration of jaundice before the onset of encephalopathy >7 days d. Cause: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions e. Prothrombin time >50 seconds (INR >3.5) f. Serum bilirubin >300 µmol/L (>17.5 mg/dL) INR = International Normalized Ratio.

8 weeks of the onset of acute liver injury. Subfulminant hepatic failure develops after 8 weeks, and the morbidity is more frequently associated with some degree of portal hypertension and renal insufficiency. Both diagnoses are associated with a high mortality rate, exceeding 80% when patients develop coma. The pathophysiology of FHF is directly related to hepatic insufficiency.66 The balance between liver cell necrosis and regeneration will determine the outcome for each patient. Other than acetaminophen poisoning, identification of a treatable etiology is uncommon in the United States, although one should be explored. A transjugular liver biopsy is the safest method to obtain tissue in FHF patients. The liver biopsy may provide information regarding the etiology as well as the severity of hepatocyte necrosis. Viral hepatitis, acetaminophen overdose, and other drug toxicities are the most common causes of FHF in North America. The majority of cases of viral-induced FHF appear to be due to non-A, non-B, non-C, and non-E hepatitis. Despite advances in supportive medical therapy, there has been little impact on the prognosis of FHF. End-organ dysfunction (renal and cardiopulmonary failure), hypoglycemia, and infection must be anticipated. Systemic and oral antimicrobials administered as prophylaxis are of benefit in delaying infection. Approximately 20% of patients with FHF will survive and go on to have normal liver function and will not develop cirrhosis.66 However, patients with FHF, progressive liver insufficiency, and encephalopathy should be cared for at a liver transplant program, as liver transplantation is the only potentially

curative therapy available today. Table 30-8 shows criteria for liver transplant candidacy in these patients. Cerebral edema and intracranial hypertension are the complications of FHF most likely to result in adverse outcome and death.67 Table 30-9 shows the clinical findings of progressive encephalopathy in FHF. As coma develops, the importance of monitoring intracranial hypertension dictates the liberal use of intracranial pressure (ICP) monitoring. This technology has been shown to be critical to the ongoing determination of a patient’s candidacy for liver transplantation. Patients whose ICP rises above 20 mm Hg or whose cerebral perfusion pressure drops below 60 mm Hg will have a high risk of irreversible brain injury and are unlikely to benefit from transplantation.68 The pathogenesis of cerebral edema in FHF is controversial, but is likely related to a combination of impaired blood flow, metabolic derangements, and increased cerebral nervous system permeability. Insight into the pathogenesis is demonstrated by the efficacy of liver transplantation in the correction of the process.69 Liver transplantation has become the therapy of choice and can improve mortality from 15% to a 1-year survival rate that exceeds 60%.69 Although 4 to 6% of all liver transplants in the United States are now performed for FHF, one third of patients listed as candidates for liver transplantation die before a donor organ becomes available. These factors have intensified the interest in the development of liver-assist devices as a bridge to liver transplantation or full recovery.70

Table 30-9 Grading of Severity of Hepatic Encephalopathy in Fulminant Hepatic Failure Level of Consciousness

Intellectual Function

Neurologic Findings

EEG

Short attention

Incoordination; mild asterixis

Slowing (5–6 cps); triphasic

2 3

Lack of awareness; personality change; day/night reversal Lethargic; inappropriate behavior Asleep; arousable

Asterixis; abnormal reflexes Asterixis; abnormal reflex

Slowing; triphasic Slowing; triphasic

4

Unarousable

Disoriented Loss of meaningful communication Absent

Decerebrate

Very slow (2–3 cps); delta waves present

Grade 1

CPS = cycles per second on EEG; EEG = electroencephalogram.

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CYSTIC DISEASES OF THE LIVER

Polycystic Liver Disease

Noninfectious cystic lesions in the liver are common throughout all decades of life. The vast majority of hepatic cysts are asymptomatic and are found incidentally. Cysts can be categorized as congenital or neoplastic.

Polycystic disease occurs as an autosomal dominant disease presenting in adulthood. An autosomal recessive process that is associated with hepatic fibrosis also occurs in rare instances in infancy. A wide spectrum of clinical and anatomic presentations is seen in polycystic liver disease (PCLD).75 Symptoms of fullness, early satiety, dysphagia, and pain are often chronic and unrelenting, and as with any consideration for liver surgery of benign processes, other contributing factors should be ruled out. Three general anatomic presentations can be described, and often a specific distribution of the cystic disease can be ascribed to specific symptoms. Some patients will have a few dominant cysts that are clearly associated with a specific symptom, usually pain, even in the presence of widespread cystic disease. Other patients will have a limited anatomic distribution of their cysts (lobar or segmental) with compensatory hypertrophy in the unaffected liver. Finally, patients can present with significant hepatomegaly and a diffuse distribution of their disease. In patients with dominant cysts and associated symptoms, PAIR should be used for the initial approach to manage symptoms. Obliteration of a treated cyst is normally seen in 80% of cases; however, careful patient selection is necessary to avoid recurrence. In patients who are not candidates for PAIR or who have failed PAIR, fenestration or resection of the cyst(s) should be undertaken based on anatomic considerations. Fenestration can be performed laparoscopically or as an open procedure, depending on the anatomic location.74 Formal lobectomy along the border of the majority of the cystic disease may be required and is expected to be associated with a durable correction of symptoms in up to 90% of carefully selected patients. In patients with massive hepatomegaly but no dominant anatomic presentation, a transverse hepatectomy (resection of segments III, IVB, V, and VI at the level of the rib cage) has been reported to be associated with excellent improvement of symptoms76 (Fig. 30-29).

Congenital Cysts Congenital cysts include simple hepatic cysts, which are the most common benign lesions found in the liver. Simple cysts result from excluded hyperplastic bile duct rests and they are commonly identified on imaging studies as unilocular, homogeneous fluid-filled structures with a thin wall without projections. The epithelium of the cyst secretes clear fluid that does not contain bile, and they rarely are symptomatic unless they are large, in which case patients may complain of pain, epigastric fullness or a mass, or early satiety related to gastric compression.71 Often these cysts are aspirated prior to surgical referral, but the recurrence rate after simple percutaneous aspiration is extremely high. Simple aspiration is not recommended as an initial therapy; however, useful information about symptom resolution is often obtained. Percutaneous aspiration, instillation of absolute alcohol, and reaspiration (PAIR) has a success rate as high as 80%.71,72 In patients with easily accessible lesions and appropriate interventional radiology support, PAIR is an excellent first line of therapy in the management of simple, congenital, hepatic cysts. The surgical management of simple cysts centers on wide cyst fenestration.73,74 These procedures are performed laparoscopically, if technically feasible. The recurrence rate after wide cyst fenestration is usually less than 5%. The excised cyst wall is sent for pathologic analysis, and the remaining cyst wall within the liver should be carefully examined for the presence of gross neoplastic changes. Cystic fluid analysis by cytology and tumor markers is not indicated unless there is concern for neoplasia. A symptomatic simple cyst rarely requires complete resection, either as an enucleation or as a formal liver resection.

FIG. 30-29. Transverse hepatectomy for symptomatic polycystic liver disease. The vascular loop is around the porta hepatis.

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

FIG. 30-30. CT scan of a large biliary cystadenoma causing pain and jaundice in a 37-year-old woman. The lesion was removed by a combination of medial enucleation of the cyst off the right portal structures and completion left hepatic lobectomy.

The most common complication specific to surgery for PCLD is ascites, occurring in all patients undergoing resection for this disease; however, it is not always symptomatic. When patients develop symptomatic ascites, diuretic use and a low-salt diet will result in nearly uniform resolution of the process. An additional concern with resection in PCLD is bile leakage. Because these cysts compress intervening hepatic parenchyma, great care must be taken to ligate any open biliary radicals, and control of any bile leakage must be sought before completion of the surgical procedure. The application of fibrin sealants to the cut surface of the liver is promising, but has not clearly been shown to prevent bile leaks. Patients who develop progressive liver dysfunction from PCLD should be considered for orthotopic or living related donor liver transplantation.

Neoplastic Cysts Neoplastic cysts are more common in women and in those individuals older than 40 years of age. These lesions are symptomatic and have a characteristic appearance on ultrasound and other axial imaging studies.77 Neoplastic cysts tend to have papillary excrescences and may have multiple loculations within the cyst (Fig. 30-30). Percutaneous aspiration is rarely indicated, but if performed will typically yield mucinous fluid. The surgical management of neoplastic cysts further relies on the initial differentiation between biliary cystadenoma and biliary cystadenocarcinoma.78 Biliary cystadenocarcinoma is uncommon and is associated with marked thickening of the cyst wall and vascular enhancement on axial imaging studies. Biliary cystadenomas can be either enucleated or resected as dictated by the anatomy.79 As with hemangiomas and PCLD, biliary cystadenomas compress the surrounding liver parenchyma and careful identification and control of the adjacent intrahepatic portal pedicles is necessary to avoid postoperative bile leakage. If any concern of biliary cystadenocarcinoma is present based on the axial imaging studies, a formal liver resection is indicated.

Other Cysts Occasionally, cystic lesions can occur in patients who have suffered liver trauma. The general appearance is that of a simple hepatic cyst, and management should be conservative.

FIG. 30-31. A ruptured hepatic adenoma in segment VII.

BENIGN SOLID LIVER TUMORS Benign solid liver tumors are increasingly identified with the more common use of axial imaging studies. Differentiation of benign tumors from malignancies including metastatic lesions is achieved based on the clinical scenario and interpretation of radiologic images.80,81 Therefore biopsy is rarely indicated.

Hepatic Adenoma Hepatic adenomas (e.g., liver cell adenoma and hepatocellular adenoma) are the most significant benign liver tumors that surgeons encounter. These lesions occur in reproductive-aged women, and are an order of magnitude more common in women who use oral contraceptive pills (OCPs).82,83 Histologically, these lesions are composed of sheets of hepatocytes with no nonparenchymal cells (Kupffer cells) or bile ducts present. Up to 75% of adenomas may be symptomatic at the time of presentation, with abdominal pain being the most common presenting symptom. Hepatocellular adenomas are significant in that they can rupture and as many as 25% of these lesions are identified after an acute episode of hemorrhage (Fig. 30-31). Radiographically, it is difficult to distinguish hepatic adenomas from focal nodular hyperplasia (FNH).84 Both lesions demonstrate rapid contrast enhancement followed by rapid washout of contrast within the tumor on CT scan and MRI. Adenomas may demonstrate increased fat signal on MRI when compared to FNH,85 and do not have a central scar, which is frequently seen in FNH. If the diagnosis is unclear following contrast-enhanced CT scan or MRI, obtaining a 99 Tc-macroaggregated albumin (99 Tc-MAA) liver scan should be considered. Typically, adenomas will be “cold” and FNH “hot” owing to the presence of nonparenchymal cells in the latter. Unfortunately, the accuracy of this radioisotope liver scan is only approximately 80%. The management of patients with hepatic adenomas is evolving. Cessation of OCPs in patients with lesions less than 4 cm in diameter is prudent. Regression of the lesion is commonly seen and such a regression may obviate or facilitate liver-directed intervention. Surgical intervention is recommended in patients with lesions larger than 4 cm in diameter, in patients whose lesions do not shrink after cessation of OCP use, those who medically cannot stop OCP use, or in patients who plan to become pregnant.86,87 RFA is another potentially effective treatment option in managing hepatic adenomas, especially in patients with multiple adenomas.

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A

1161

B FIG. 30-32. Focal nodular hyperplasia. A . Contrast-enhanced MRI reveals a hypervascular lesion with a central scar located in segments IVA and VIII. B . Resected specimen showing the characteristic central scar.

However, until further follow-up data of this technology are available, resection remains the standard therapy. A number of patients with large adenomas undergoing resection have been found to have foci of well-differentiated hepatocellular carcinoma, although large longitudinal studies have not supported a strong association between OCP use and hepatocellular carcinoma.88

Focal Nodular Hyperplasia In contrast to hepatic adenomas, focal nodular hyperplasia typically is not associated with symptoms and does not pose any risks of rupture or malignant degeneration.84 These lesions intensely enhance on the arterial vascular phase of axial imaging studies (Fig. 30-32). Characteristically, up to two thirds of lesions will demonstrate a central scar. The lesions are often peripherally located and histologically composed of regenerative nodules with hyperplastic bile ducts and connective tissue septae. The etiology is thought to be a result of an early embryologic vascular injury and the histologic findings are a response to this event. FNH is rarely symptomatic. Therefore other etiologies for symptoms should be explored. In patients with symptoms related to FNH, resection is indicated. Because the lesions are often peripheral, minimally invasive (laparoscopic) approaches to resection should be advocated for the experienced surgeon.89 Resection of the lesion with a thin margin of normal liver parenchyma is curative, but formal segmental resection should be considered, as such procedures are associated with lower morbidity.

A

Hemangiomas Hemangiomas, also known as cavernous hemangiomas, are common benign liver lesions generally discovered incidentally on axial imaging studies. Patients with hemangiomas may present with chronic low-intensity right upper quadrant abdominal pain, especially when the lesions are quite large.90 Ultrasound can be helpful in identifying hemangiomas, but a CT scan or contrastenhanced MRI are diagnostic. CT and MRI will demonstrate peripheral nodular contrast enhancement followed by gradual centripetal enhancement, and finally washout of contrast in the lesion on further delayed films (Fig. 30-33). On MRI, these lesions will be bright on T2-weighted evaluation. In rare instances, hemangiomas are difficult to differentiate on MRI and are termed

B FIG. 30-33. Hemangioma of the liver. A . Contrast-enhanced MRI demonstrating peripheral nodular enhancement. B . Bright signal characteristics of the same lesion on T2-weighted MRI.

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atypical hemangiomas. An atypical hemangioma can be further evaluated using 99 Tc-labeled red cell study. Angiography is rarely necessary. As with other benign lesions, when symptoms are present other causes of abdominal pain should always be ruled out. Resection can be recommended if symptoms can be clearly ascribed to a large hemangioma. Hemangiomas can be resected by enucleation or more standard formal liver resection.91,92 Enucleation of hemangiomas follows the line of compressed liver tissue, and great care must be taken to ensure control of any biliary radicals that are opened in the process.

Bile Duct Hamartomas Bile duct hamartomas are the most common liver lesions seen at laparotomy. Hamartomas are peripheral in location, and are firm, smooth, and white in appearance. They are less than 1 cm in size and usually only 1 to 3 mm in diameter. The lesions can be difficult to differentiate from miliary metastatic lesions, especially those derived from colorectal cancer and bile duct cancers. Biopsy is indicated for grossly equivocal lesions.

LIVER INFECTIONS The liver parenchyma is constantly exposed to a low level of enteric bacteria through the portal blood flow; however, liver infections are rare. The liver is the largest repository of the reticuloendothelial system and is therefore able to cope with this constant barrage. When the inoculum exceeds the capacity for control, infection and abscess occur. Liver abscess can be ascribed to two categories: pyogenic or parasitic.

Pyogenic Liver Abscesses Pyogenic liver abscesses have been well known for over 100 years and were a common cause of morbidity and mortality in patients with untreated appendicitis and pylephlebitis. Currently, the most common etiologies of pyogenic liver abscesses include biliary tract manipulation, diverticular disease, inflammatory bowel disease, and systemic infections such as bacterial endocarditis.93−95 Rarely, endoscopic retrograde cholangiography for ascending cholangitis or the management of biliary strictures may result in liver abscess.96 Patients with contrast material injected proximal to undrained strictures are at high risk. The performance of targeted drainage after an initial noninvasive diagnostic magnetic resonance cholangiogram can aid in avoiding this complication. The clinical presentation of patients with pyogenic liver abscesses is rarely subtle. Patients present with right upper quadrant abdominal pain, fever, and occasionally jaundice.95 A careful history and physical examination are necessary to elicit findings of less obvious etiologies such as mild diverticular disease and poor dentition. In patients with chronic symptomatology, fever and weight loss with progressive fatigue may be seen. Significant liver test abnormalities are relatively uncommon and are typically mild. Interestingly, as many as one third of patients with pyogenic liver abscesses will not have an identifiable primary source of infection. Ultrasound examination will demonstrate a cystic mass in the liver, often with multiple complex septations or inhomogeneous fluid characteristics. In patients who present with abnormalities on ultrasound, an axial imaging study with intravenous contrast should follow. CT findings will include a complex hypodense mass with peripheral enhancement (Fig. 30-34). In patients with a solitary dominant abscess, percutaneous aspiration with evaluation by

FIG. 30-34. Left lobe hepatic abscess in a patient who underwent biliary tract instrumentation for common bile duct stones.

Gram’s stain and culture is essential to direct further antimicrobial and drainage therapy.97 In patients with solitary abscesses, aspiration alone may be sufficient if the abscess can be significantly drained. The placement of a percutaneous drainage catheter at the time of aspiration is beneficial for patients with a complex abscess or an abscess containing particularly thick fluid. Occasionally patients presenting with multiple small abscesses are not amenable to percutaneous sampling. Under such circumstances, laparoscopic evaluation of the liver, including IOUS and a focused biopsy, can be beneficial.98 In an immunosuppressed patient who has multiple abscesses, hepatosplenic candidiasis should be considered, as well as more conventional pyogenic etiologies (Fig. 30-35). The radiologic diagnosis of hepatosplenic candidiasis can be made based on serial MRI findings. Operative exploration should be reserved for indeterminate cases. In patients with intra-abdominal sources leading to hepatic abscesses, Gram-negative aerobes, Gram-positive aerobes, and

FIG. 30-35. Multiple small abscesses consistent with hepatosplenic candidiasis in a bone marrow transplant recipient.

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A

FIG. 30-36. Hydatid disease of the liver. A . Life cycle of Echinococcus granulosus. B . Hydatid cyst contents. (Courtesy of Dr. William Gamble.)

B anaerobes are the predominant organisms found in liver abscesses. Commonly encountered organisms include Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis and faecium, and anaerobic or facultative anaerobic species such as Bacteroides fragilis. In patients with systemic infections from subacute bacterial endocarditis and indwelling catheter infections, Staphylococcus and Streptococcus species are more common. Monomicrobial abscesses are found in approximately 40% of patients, an additional 40% are polymicrobial, while the remaining cases are culture negative. Antimicrobial therapy should be empiric, based on the etiology of the primary infection from the culture results following aspiration of the abscess. Since percutaneous aspiration is effective in 80

to 90% of patients, surgical intervention is typically unnecessary. However, when percutaneous drainage fails, laparoscopic or open surgical drainage may be necessary. Rarely, in patients with recalcitrant lesions, formal liver resection may be necessary.

Parasitic Liver Abscesses Hydatid Disease Cystic hydatid disease is caused by the larval/cyst stage of Echinococcus granulosus, in which humans are an intermediate host (Fig. 30-36A). Humans are infected by oral ingestion of excrement from animals (most commonly canines). This form of hydatid

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disease occurs throughout the world, predominantly in the Southern Hemisphere, Europe, Russia, and China. Hydatid cysts can be uncomplicated and asymptomatic. However, these lesions may rupture, can become secondarily infected, or may infect other organs. The diagnosis is based on an enzyme-linked immunosorbent assay (ELISA) test for echinococcal antigens, which is positive in over 85% of infected patients.99 Ultrasound and CT scanning will typically demonstrate either simple or complex cysts with a cyst wall of varying thickness. The treatment of hydatid disease involves the use of oral anthelmintics such as albendazole. Albendazole therapy is the mainstay of treatment in the majority of patients with hydatid disease. It is given alone and for prolonged periods of time in patients who are poor candidates for cyst-directed intervention. However, liver-directed treatment is preferred. In patients with anatomically appropriate lesions PAIR is the preferred initial treatment.100 The efficacy of PAIR in managing hydatid cysts is greater than 75%. For patients whose disease is refractory to PAIR, laparoscopic or open complete cyst removal with instillation of a scolicidal agent generally is curative (see Fig. 30-36B).101,102 If surgical cystectomy with removal of the germinal laminated layers is not technically feasible, then formal liver resection can be employed. During aspiration or surgical treatment of hydatid cysts, extreme caution must be taken to avoid rupture of the cyst with release of protoscolices into the peritoneal cavity. Alveolar echinococcosis (Echinococcus multilocularis) occurs in the Northern Hemisphere, produces a more generalized granulomatous reaction, and can present in a manner similar to a malignancy. Resection is the treatment of choice.

Amebiasis Entamoeba histolytica enters into humans in a cyst form but transforms into a trophozoite in the colon.103 It enters into the colonic mucosa and invades the portal venous system, infecting the liver. Amebic abscesses result from local proteolytic destruction of the liver parenchyma with focal infarction. Amebiasis is a disease found in subtropical climates, especially in areas with poor sanitation. Although resulting from a colonic infection, a recent history of severe diarrhea is uncommon. Patients typically present with sweating and chills, usually of at least 1 week duration. Fevers can be high and patients typically have right upper quadrant abdominal pain and tenderness. The majority of patients have a positive fluorescent antibody test for E. histolytica as well as mild abnormalities in liver enzymes; hyperbilirubinemia is relatively uncommon. In patients who live in or who have recently visited an endemic area and who present with right upper quadrant tenderness and hepatomegaly, an ultrasound showing an abscess should be considered diagnostic for the presence of amebiasis.104 Patients diagnosed with amebic liver abscesses should be treated with metronidazole for at least 1 week. Most patients will respond rapidly with complete defervescence within 3 days. Aspiration of the abscess is rarely necessary and should be avoided, except in patients in whom secondary infection from pyogenic organisms is suspected.105

EVALUATION OF FUNCTIONAL HEPATIC RESERVE Patients with normal hepatic parenchyma and serum liver tests can tolerate resection of as much as 80% of their liver volume. The remaining 20% of normal, perfused liver has the metabolic capacity to provide adequate hepatic function while liver regeneration occurs. However, patients with abnormal liver function related to extensive fatty infiltration or cirrhosis, most commonly caused by

chronic ethanol ingestion or chronic hepatitis B or C viral infections, may not tolerate resection of a significant proportion of the liver and are at increased risk for postoperative liver insufficiency or liver failure and death. The size, number, and location of liver tumors will mandate the type of operation that must be performed to achieve a margin-negative resection. A significant amount of hepatic parenchyma is lost with major liver resections. The average amount of liver parenchyma resected during a right trisegmentectomy is 85%, a right lobectomy 65%, a left lobectomy 35%, and segmental or wedge resections involve a loss of 3 to 15%. In patients with abnormal liver function who are being considered for partial hepatic resection of malignant disease, assessing the functional hepatic reserve should be considered to determine the patient’s risk for postoperative liver failure. Patients with cirrhosis who develop HCC should undergo assessment of functional hepatic reserve. It may also be appropriate to evaluate functional hepatic reserve in patients with primary or metastatic liver tumors who have significant fatty infiltration of the liver, and in those undergoing resection of an extensive portion of the hepatic parenchyma, such as a right trisegmentectomy. Assessing the risk of postoperative liver failure based on a clinical classification system, such as the Child class (see Table 30-3) alone is inadequate; the postresection mortality rate from liver failure for Child class A or B patients ranges from 8 to 25%.109 In cirrhotic patients being considered for resection of malignant liver disease, the addition of quantitative or functional hepatic studies can improve patient selection, determine the extent of hepatic parenchymal resection that will be tolerated, and reduce the postoperative mortality rate from liver failure to between 0 and 5%. Functional studies of the liver employ compounds that normally are rapidly acquired and metabolized or cleared by hepatocytes. Rates of metabolism and clearance are decreased in cirrhotic or diseased livers. Some of the compounds used in functional studies have a clearance rate that is determined principally by the route of delivery rather than metabolism. Hence these compounds reflect changes in hepatic microcirculation and reduction in hepatic blood flow associated with cirrhosis. Other compounds are less affected by blood flow rates, and their metabolism is a more accurate indicator of functional hepatocyte mass. The most commonly used test to assess functional hepatic reserve is indocyanine green (ICG) clearance. ICG is an anionic dye bound by plasma lipoproteins which is rapidly cleared by the liver and excreted unconjugated in bile.110 Hepatic clearance is limited by both the hepatic blood flow rate and uptake by hepatocytes. Following an intravenous bolus of ICG, the kinetics of its disappearance from plasma due to hepatic clearance can be used to estimate the functional hepatic reserve in patients with cirrhosis or extensive fatty infiltration, even in the presence of hyperbilirubinemia. ICG clearance determinations are widely used and readily available. The ICG clearance values can be used to predict risk of liver failure and mortality following major hepatic resection in the majority of cirrhotic patients. However, there are two principal disadvantages of ICG clearance. First, this test is not a true measure of hepatocyte function, as ICG delivery to the liver is limited in part by the reduced blood flow to the cirrhotic liver. Second, for patients whose values fall in the middle of the ICG clearance risk assessment range, the tests cannot accurately predict a given individual’s risk for postoperative liver failure and death. This is particularly true if the patient will require more than a simple wedge or segmental resection to remove the malignant liver disease. There are several tests that assess functional hepatic reserve that are not dependent upon hepatic blood flow rate. These tests can provide a more accurate measure of hepatocyte uptake and metabolism. The aminopyrine and phenylalanine

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breath tests are noninvasive and reasonably simple to perform. The patient ingests an oral dose of radiolabeled [14 C] aminopyrine or L-[13 C] phenylalanine, then the individual breathes into an apparatus that collects expired CO2 at intervals for up to 2 hours after the radiolabeled compound is ingested. The amount of exhaled 14 CO2 or 13 CO2 is then used to calculate the percentage of the original aminopyrine or phenylalanine dose undergoing hepatic demethylation or oxidation. Another test of hepatocyte microsomal capacity involves an intravenous injection of galactose followed by serial measurement of serum galactose levels to determine hepatic clearance of galactose. This test is not affected by altered hepatic blood flow rates that may occur with cirrhosis. Both of the radio label tracer studies and galactose eliminate rate have been shown to increase the predictive accuracy of postoperative liver failure in cirrhotic patients with borderline abnormal ICG clearance rates.109−111 Administering a known intravenous dose of lidocaine to determine the rate of hepatic microsomal metabolism of lidocaine to monoethylglycinexylidide (MEGX) is another method of evaluating liver function.112 This test is less expensive, simpler, and provides an assessment of functional hepatic reserve more rapidly than other clearance studies. A measurement of the levels of MEGX in the serum 15 minutes after an intravenous injection of lidocaine (1 mg/kg) is useful in distinguishing patients with mild liver dysfunction from those with cirrhosis, but MEGX levels are not as accurate in predicting severity of cirrhosis when compared with the aminopyrine breath test or galactose elimination capacity. Unfortunately, measurements of metabolites like MEGX, galactose, aminopyrine, and phenylalanine, that are quantitative liver tests based on microsomal metabolism, may quantitate only particular enzymatic reactions. Thus these specific pathways may not be representative of the entire functional hepatic reserve. Nonetheless, using one or several of these tests in addition to ICG clearance can be useful in selecting patients to undergo partial hepatectomy who are at low risk of developing postoperative liver failure, despite the presence of a fatty or cirrhotic liver. A recent prospective study of 61 cirrhotic patients being considered for resection of HCC used the hippurate ratio, a novel measurement of glycine conjugation of para-aminobenzoic acid to hippurated metabolites by the liver, as a preoperative study of functional hepatic reserve.113 The hippurate ratio was compared to ICG clearance in the same patient population. ICG clearance rates did not predict the patients who developed postoperative liver failure, including three deaths; however, the hippurate ratio was an accurate predictor of liver failure. Although an interesting initial study, its results will need to be confirmed in a larger group of patients, as only 35 of the 61 cirrhotic patients actually underwent liver resection. An additional application for nuclear medicine studies is the development of new compounds to assess functional hepatic reserve. Dynamic single photon emission computed tomography (SPECT) images have been used following intravenous injection of 99m Tcgalactosyl-serum albumin (GSA) to assess functional hepatic reserve in patients with chronic liver disease before and after liver resection.114 Initial results showed a good correlation between total hepatic 99m Tc-GSA clearance and conventional hepatic studies including ICG clearance, cholinesterase levels, and hepaplastin tests. A total of 114 patients were studied, including 55 who underwent hepatic resection for malignant liver tumors. In the five patients who developed postoperative liver insufficiency, 99m Tc-GSA clearance accurately predicted liver failure in each of the patients. PET using H(15) 2 O has recently been shown to be a noninvasive method to measure portal venous and hepatic arterial blood flow.115 There was excellent correlation between portal blood flow and severity of

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cirrhosis. This technique will now be studied as a prognostic indicator in patients with cirrhosis who are undergoing liver resection for malignant disease.

MALIGNANT LIVER TUMORS Surgical Treatment The first recorded successful elective resection of a liver tumor in the United States was performed by Tiffany in 1890, followed in 1891 by Lucke in Europe.106 If they were not already aware of the risk of massive hemorrhage from the liver, surgeons were reminded of it by Elliot in 1897 in his report of an attempted resection of a liver tumor, when he stated that the liver “is so friable, so full of gaping vessels and so evidently incapable of being sutured that it seemed impossible to successfully manage large wounds of its substance.”107 Most surgeons continued to choose judiciously which patients they would consider for an elective liver resection, if any, until a greater understanding of hepatobiliary anatomy was published by Couinaud in 1954.108 Couinaud’s description of the segmental liver anatomy based on portal venous inflow and hepatic venous outflow, and the identification of eight hepatic segments (numbered I through VIII) were key steps in the development of safe, anatomic hepatic resections (see Fig. 30-1; Fig. 30-37). Building on the anatomic and surgical foundation laid down by investigators 50 to 100 years ago, modern surgeons are performing elective operations for liver tumors with increasing frequency. The persistent interest in improved and safer surgical treatments for malignant liver tumors is based on the fact that surgical extirpation or complete cytodestruction currently provides patients with the best chance for long-term disease-free and overall survival. This is true for disease confined to the liver, whether treating patients with primary or metastatic liver cancers. Improved preoperative imaging studies, routine use of intraoperative ultrasonography, understanding of the vascular and segmental anatomy of the liver, application of new surgical instruments and technology, and improved perioperative anesthesia management have combined to increase the number of patients undergoing successful hepatic resections as treatment for primary or metastatic liver tumors. HCC is one of the most common solid human cancers, with an annual incidence estimated to be approximately 1 million new patients.116,117 In addition to being a common site for the development of primary malignancy, the liver is second only to lymph nodes as a common site of metastasis from other solid cancers.118 It is not uncommon, particularly in patients with colorectal adenocarcinoma, for the liver to be the only site of metastatic disease. Surgical resection of HCC, colorectal cancer hepatic metastases, and carefully selected patients with liver-only metastases from other types of primary tumors can result in significant long-term survival benefit in 20 to 45% of patients.119,120

Indications for Resection The important role of liver resection as a treatment for colorectal cancer metastases was solidified by the report in 1988 from the Registry of Hepatic Metastases.121 This retrospective chart review from 24 institutions identified 859 patients who underwent resection of colorectal liver metastases between 1948 and 1985. The 5-year actuarial survival rate in these patients was 33%, with a 5-year actuarial disease-free survival rate of 21%. Several indicators of poor prognosis also were established by a subset analysis, including a 0% 5-year survival rate when extrahepatic metastatic disease was present, a significantly reduced survival rate if the tumor-free

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Middle hepatic vein Right hepatic vein IVC

Left hepatic vein

II VIII VII

IVa

III

IVb V VI Portal vein

Inferior vena cava

resection margin was less than 1 cm or if the primary tumor was stage III (node positive) versus stage II (node negative), and reduced 5-year overall and disease-free survival rates in patients who underwent resection of three or more metastases. The authors noted that patients with three metastases had a significantly poorer disease-free survival rate than those with a single metastasis or two metastases, and that patients with four or more metastases appeared to do at least as poorly. Based on those observations, the presence of four or more liver metastases from colorectal cancer became a contraindication to resection, even when technically feasible with an adequate remaining volume of perfused hepatic parenchyma. The Registry of Hepatic Metastases report is a retrospective review of patients who underwent operation largely before the availability of adequate preoperative and intraoperative imaging modalities. Furthermore, careful pathologic analysis and an accurate count of the number of lesions were not available in all of the patients. Most of the patients were identified by the development of symptoms, abnormalities in serum liver tests, or an elevated serum tumor marker in the later period of the study. The study included 509 (59%) patients with a solitary liver metastasis, indicating that this was a highly selected group of patients. Of the 149 patients who had three or more metastases, a breakdown of survival by number of metastases was not provided, and the actuarial 5-year survival rate for this group was 18%.121 Recent re-evaluations of the number of metastases that should be considered for resection have demonstrated that there is a potential survival benefit in patients with four or more metastases. In contrast to the registry data, all patients in these modern series underwent thorough intraoperative ultrasonography to detect metastatic foci within the liver not identified by preoperative imaging studies, as well as to ensure that the resection be performed with a high probability of tumor-free margins. A study of 235 patients from Japan who underwent hepatic resection for metastatic colorectal cancer included 53 patients (22.6%) who had more than four metastases, including some patients with as many as 10 to 15 lesions.122 The actuarial 10-year life expectancy of patients with four or more lesions was 29%, which was almost equivalent to the long-term survival of

FIG. 30-37. Segmental liver anatomy and nomenclature for lobar, segmental, and extended liver resections. (Adapted from www.ahpba.org, the Web site of The American Hepato-Pancreato-Biliary Association.)

patients who underwent resection of a solitary metastasis. Patients with two or three metastases actually had a slightly worse long-term survival than patients with more than four tumors. A study from the United States of 155 patients who underwent resection of more than four colorectal liver metastases revealed an overall 5-year survival rate of 23%.123 As the number of resected metastases increased above nine, there was a significant reduction in long-term survival probability. On multivariate analysis, only positive resection margins and a large number of metastases were significant prognostic indicators for poor outcome. The indications for resection of HCC also have been reevaluated. Studies from the 1980s and early 1990s suggested that the presence of cirrhosis or multiple tumors were harbingers of poor outcome after resection of HCC.109 However, these studies were performed during a time when operative mortality rates in cirrhotic HCC patients ranged from 6 to 15%, and the need for intraoperative and postoperative blood transfusion was common. Improved outcomes have been demonstrated in more recent studies in which modern hepatic resection techniques were employed.124,125 Specifically, perioperative blood transfusion rates fell from 69 to 87% in the earlier time period to 23 to 39% in more recent series. The operative and hospital death rate was reduced from 13.2% to under 2%, and 5-year survival rates improved from 19 to 32% to 25 to 49%, despite all patients harboring pathologically proven cirrhosis.124

Stapling Devices in Liver Resection Vascular staplers can be used in properly selected patients to reduce operative time and intraoperative blood loss.126 Hepatic inflow and outflow control can be achieved with stapling devices. However, these techniques should be applied judiciously and should not be used if a tumor must be divided near the vasculature because of the significant negative prognostic impact of positive tumor margins. When a hepatic tumor is near the main right or left portal vein branches, the traditional technique of extrahepatic dissection in the porta hepatis with ligation of the portal vein, hepatic artery, and bile duct branch to the affected lobe should be performed.

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IVC

RHV MHV LHV

HA

FIG. 30-38. Transparenchymal vascular stapling techniques in the liver can be performed safely using intraoperative ultrasonography to demonstrate the location and association of branches of the portal vein (PV), the right hepatic vein (RHV), the middle hepatic vein (MHV), and the left hepatic vein (LHV). Transparenchymal stapling of hepatic inflow vessels also controls hepatic arterial (HA) as well as bile duct (BD) branches.

CBD

(Figs. 30-38 through 30-42). The stapler is introduced at the junction of segments IVB and V and exits posteriorly in segment VII; this maneuver is safe only if the right lobe of the liver has first been fully mobilized and the direct venous branches from the posterior aspect of the liver into the vena cava have been individually ligated and divided. The vascular Endo-GIA stapler can also be used to ligate and divide the inflow blood supply during left hepatic lobectomy (see Fig. 30-39; Figs. 30-43, 30-44, and 30-45), or

A major advantage of stapling techniques is intrahepatic ligation and division of the vascular inflow to a lobe. A key point in the safe use of staplers for hepatic resection is that complete mobilization of the lobe to be resected is required. This is true whether achieving inflow control of the portal pedicles or outflow control of the major hepatic veins.127 A vascular stapler can be used to divide the blood supply to the right hepatic lobe after performing cholecystectomy to establish the inferior liver surface landmarks

FIG. 30-39. An illustration demonstrating the anterior and inferior aspect of the liver following removal of the gallbladder. Transparenchymal stapling of the inflow blood supply and bile ducts to the right lobe of the liver is facilitated by using electrocautery to score the capsule of the liver along the medial aspect of the gallbladder fossa (GBF) as denoted by [ A ]. Transparenchymal stapling of the blood supply and bile ducts to the left lobe of the liver is facilitated by using electrocautery to score the liver capsule inferiorly at the hilar plate as denoted by [ B ].

A

GBF

PV

B

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MHV

MHV MHV

RPV RBD RHA

RPV RPV

FIG. 30-40. Illustration demonstrating the maneuvers used to perform transparenchymal stapling for a right hepatic lobectomy. The right lobe of the liver has been completely mobilized from its attachments to the retroperitoneum and the diaphragm, and all small direct perforating branches from the posterior aspect of the liver to the inferior vena cava have been ligated and divided. Through the score mark on the liver capsule along the medial aspect of the gallbladder fossa as denoted by [ A ] in Fig. 30-39, a long, fine dissecting clamp is used to gently push through the hepatic parenchyma superiorly for 3 to 5 cm, and then the clamp is directed posteriorly to exit in segment VII, just lateral to the inferior vena cava. This maneuver encircles the right portal vein (RPV), right bile duct (RBD), and right hepatic artery (RHA). It is imperative to use intraoperative ultrasonography to determine the length of superior dissection in the liver to encircle the inflow blood supply and bile duct to the right lobe of the liver, as well as to ensure that the clamp passes inferior and posterior to the middle hepatic vein branches (MHV) to avoid injury and hemorrhage from these branches.

FIG. 30-41. A suture is grasped and pulled back through the track by the clamp that was used for intraparenchymal dissection around the inflow blood vessels and bile duct to the right hepatic lobe. This suture encircles the vessels and bile duct and is used to guide placement of one piece of the vascular Endo-GIA stapler, as demonstrated in this illustration. Again, it is key to pass the stapler using the suture as a guide through the proper track to encircle the right portal vein (RPV) as well as the right hepatic artery and right bile duct, while also avoiding injury to middle hepatic vein (MHV) branches.

when resecting segments II and III of the liver, a so-called left lateral segmentectomy. The low profile, flexible neck, and long handle of a vascular Endo-GIA stapler makes it ideal for outflow control with ligation and division of the hepatic veins. This technique is used most commonly for the right hepatic vein (Fig. 30-46), but with proper hepatic mobilization and division of the parenchyma around the vessels, the middle and left hepatic veins also can be divided using this device.127 Control of the inflow and outflow vessels of the lobe to be resected allows division of the hepatic parenchyma in a relatively bloodless field (Figs. 30-47, 30-48, and 30-49).

Laparoscopic Hepatic Resection Laparoscopy has a definite role in the diagnosis and staging of patients with gastrointestinal malignancies. A therapeutic role for laparoscopic liver resection has yet to be established. The development of endoscopic vascular staplers and the harmonic scalpel have increased interest in laparoscopic approaches to benign and malignant liver tumors, although minimally invasive liver resection has not advanced as far as laparoscopic colon, adrenal, and spleen resection. Over the last several years, small series of patients treated with laparoscopic liver resection have been reported. The large majority of liver resection cases completed laparoscopically have been left lateral segmentectomies, segmental or partial segmental resections,

FIG. 30-42. This illustration demonstrates that the second piece of a vascular Endo-GIA stapler has been joined to the end of the stapler that was passed transparenchymally to encircle the right portal vein, right hepatic artery, and right bile duct. The stapler is fired and released, ligating and dividing the inflow blood supply and bile ducts to the right lobe of the liver.

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RHV

IVC

FIG. 30-43. After the inflow blood supply and bile duct to the right lobe of the liver has been ligated and divided as demonstrated in Fig. 30-42, this illustration demonstrates the previously completed dissection along the inferior vena cava (IVC) to expose the right hepatic vein (RHV). This dissection is done prior to dividing the inflow blood supply to the right lobe of the liver, both to ligate any small perforating branches from the liver to the inferior vena cava, and to dissect and encircle the right hepatic vein with a vessel loop. After the inflow blood supply to the right hepatic lobe has been divided, the RHV is divided with a single application of an Endo-GIA vascular stapler as denoted in the top right side panel. After the stapler is fired and released, the RHV is ligated and divided as seen in the lower right panel.

or wedge resections.128,129 Laparoscopic ultrasonography is performed to localize tumors and to mark the surface of the liver with electrocautery to ensure an adequate margin-negative resection. The parenchyma can be transected using endovascular staplers, the harmonic scalpel, or with finger fracture through a hand port using a pneumosleeve. The reasons for converting a laparoscopic to an open liver resection include dense adhesions that preclude adequate laparoscopic visualization, inadequate tumor-free margins, or brisk hemorrhage during laparoscopic resection.

Repeat Hepatectomy for Recurrent Malignant Tumors

FIG. 30-44. This illustration demonstrates the devascularized right lobe of the liver which lies between segments IVA and IVB (medial segment of the left lobe of the liver) and segments V and VIII as seen in this anterior view. Transection of the hepatic parenchyma is initiated by placing two no. 1 chromic liver sutures on either side of the zone of demarcation between vascularized and devascularized liver. The parenchyma compressed by these sutures is then divided with electrocautery and the capsule of the liver is scored and divided with electrocautery to a depth of 2 to 3 mm along the line of vascular demarcation.

The long-term, disease-free survival rates for patients undergoing surgical resection of primary or metastatic liver tumors is usually below 40% in the most optimistic reports, and may be below 20% in others. Clearly, the majority of patients develop recurrent malignant disease after hepatic resection. In a subset of these patients, the only site of recurrence will be new tumor deposits in the liver. Yet a further subset of these patients may have undergone significant hepatic regeneration and have tumors in locations amenable to repeat liver resection. The group of patients most frequently considered for repeat hepatectomy are those with recurrent colorectal metastases.130,131 Only 10 to 15% of patients who develop recurrent disease after liver resection for colorectal metastases will be considered as candidates for a second or third resection. The incidence of extrahepatic disease

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FIG. 30-45. Transection of the remaining hepatic parenchyma can be performed using a variety of techniques. This illustration demonstrates use of the CUSA (Cavitron Ultrasonic Aspirator) device. Vessels bridging between the left lobe and right lobe of the liver are exposed during this dissection and can be divided between hemoclips, as demonstrated in the inset illustration in the upper left, or can be tied or suture ligated.

in patients being considered for repeat hepatectomy may be as high as 30%; thus they should undergo thorough preoperative evaluation with state-of-the-art helical CT imaging and PET scans.131 While technically challenging because of adhesions and altered vascular anatomy related to the previous hepatic resection, repeat hepatectomy can be performed with low morbidity and mortality rates. At the M.D. Anderson Cancer Center in Houston, Texas, these authors experienced 23 patients with colorectal cancer metastases who underwent a repeat resection with no perioperative deaths and a 22% complication rate.130 The median survival in this small group of patients was 39 months, but the 5-year survival rate was only

13%. In contrast, other authors report 5-year survival rates of up to 35%, attained with similar low operative morbidity and mortality rates.131 Repeat hepatic resection may also be applied in selected patients with HCC. Intrahepatic recurrence as the only site of disease is more common in HCC patients than those with metastatic liver tumors, but the number of patients who are candidates for repeated surgical treatment is less than 10% of those who develop recurrent disease. Patients who develop hepatic recurrence of HCC after hepatic resection of their primary tumor may not be candidates for repeat resection because of multifocality, vascular invasion by tumor, or the severity of underlying cirrhosis. In properly selected patients, repeat hepatic resection for HCC can be performed and result in long-term survival rates of up to 30%.132,133 The incidence of postresection liver failure is no higher in patients who undergo a second hepatic resection, indicating the importance of carefully selecting individuals who will have adequate functional hepatic reserve following a second operation.

Portal Vein Embolization

FIG. 30-46. Illustration demonstrating a completed right hepatic lobectomy, with the right portal vein, right hepatic artery, and right bile duct ligated and divided with vascular Endo-GIA staplers, and the right hepatic vein ligated and divided with an Endo-GIA vascular stapler. Middle hepatic vein branches can be controlled with additional firings of the vascular Endo-GIA stapler or with suture ligatures.

Direct tumor invasion of a lobar portal vein branch may lead to ipsilateral hepatic lobe atrophy and contralateral lobe hypertrophy. The development of compensatory hypertrophy of a lobe or segments of the liver following tumor occlusion of contralateral portal venous branches led to the concept of planned portal vein embolization (PVE) to initiate hypertrophy in segments of the liver that would remain following a major liver resection. PVE was first reported as a potentially useful treatment to induce hepatic hypertrophy prior to liver resection in a small group of HCC patients in 1986.134 These patients also were treated with hepatic arterial embolization of their primary liver tumor, but PVE was noted to induce hypertrophy rarely seen with hepatic arterial embolization alone. Interest in preoperative PVE has increased because extended hepatectomy (resection of five or more hepatic segments) is now more commonly considered an appropriate and safe treatment option in patients with hepatobiliary malignancies. Surgical mortality from extended hepatic resections continues to be reduced as a result of improved patient selection and safer surgical and anesthetic techniques. However, complications related to postoperative hepatic insufficiency, including cholestasis, coagulopathy, bleeding, fluid retention, and impaired hepatic synthetic function, may cause a

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LPV

FIG. 30-47. Illustration demonstrating key anatomic points for performing a left hepatic lobectomy utilizing vascular staplers. The hilar plate of the liver is scored with electrocautery and opened along the line denoted [ B ] in Fig. 30-39. Similarly to the technique used for the right hepatic lobectomy, a long, slightly curved dissecting clamp is used to gently push through the hepatic parenchyma, exiting posteriorly in segments II and III just above the caudate lobe (segment I). A suture is pulled through this same track and is used as a guide to ensure that the stapler is placed around the left portal vein (LPV), left hepatic artery, and left bile duct, while avoiding injury to the inferior vena cava.

IVC

FIG. 30-48. After dividing the vascular inflow blood supply and the bile duct to the left lobe using an Endo-GIA vascular stapler, the left lobe demarcates and becomes darker than the still vascularized right lobe of the liver. Once again, the dissection is initiated by placing two no. 1 chromic liver sutures on either side of the zone of demarcation, tying these down, and then dividing the parenchyma between these sutures with electrocautery.

Caudate

FIG. 30-49. A completed left hepatic lobectomy resecting segments II, III, and IV. Unlike right hepatic lobectomy, in which the right hepatic vein is dissected and divided in its extrahepatic portion, branches of the middle hepatic vein and left hepatic vein are divided intraparenchymally using additional firings of the vascular Endo-GIA stapler.

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prolonged hospital stay and protracted recovery following extended hepatectomy.135 Furthermore, during preoperative evaluation of patients for an extended hepatectomy, some patients will be excluded from the benefit of a potentially curative resection because the anticipated liver remnant will be too small.

Indications for Portal Vein Embolization In patients with normal hepatic parenchyma, preservation of a perfused section of liver comprising 25% of the total hepatic volume is usually sufficient to prevent major postoperative complications and hepatic insufficiency. This 25% value has been determined somewhat empirically, and there is a paucity of data regarding the exact volume of liver that can be resected safely without postoperative liver failure when the remaining liver parenchyma is completely normal. In a recent series of 20 patients with normal liver parenchyma who underwent an extended right hepatic lobectomy, it was demonstrated that a future liver remnant of 25% or less of the total liver volume was associated with increases in severity of postoperative liver insufficiency, length of stay, and complications.136 Another recent report described the results with extended liver resection in 55 patients with normal hepatic parenchyma.137 Based on preoperative calculation of a future liver remnant that was 25% or less of the total liver volume, 18 of these patients underwent preoperative PVE. The median increase in the future liver remnant was 8%. As a result of the increase in the future liver remnant in the PVE group, there was no difference in the immediate preoperative volume of the future liver remnant between the PVE group (23% future liver remnant) and the group that did not receive preoperative PVE (25% future liver remnant). Importantly, there was no difference in the occurrence of major postoperative complications or length of stay between the two groups. Thus, preoperative PVE allowed a safe liver resection in 18 patients who otherwise would not have been candidates for an extended hepatic resection, and the median survival time following liver resection in the patients treated with PVE was not significantly different from those patients who did not require PVE.137 The functional capacity of liver compromised by cholestasis, acute or chronic inflammation, steatosis, or cirrhosis is variable. A larger future liver remnant is required to avoid posthepatectomy hepatic insufficiency or failure in patients with diseased hepatic parenchyma. Two recent studies suggest that at least 40% of the total hepatic volume should remain in order to minimize postoperative complications in patients who have underlying chronic liver disease or who have received high-dose chemotherapy.138,139 In addition to preoperative PVE, patients with underlying chronic liver disease also may require careful assessment of functional hepatic reserve before and after PVE to assess the risk of postoperative liver failure.

Preoperative Volumetric Determination of the Future Liver Remnant Rapid-sequence, thin-section, helical CT is used to make direct measurements of total liver volume, volume of the liver to be resected, and volume of the future liver remnant (Fig. 30-50).136 The total liver volume also can be estimated based on the described association between body surface area (BSA) and the total liver volume, where total liver volume = 706.2 × BSA (in m2 ) + 2.4.140 The future liver remnant volume, for example the volume of segments I, II, and III in a patient undergoing an extended right hepatectomy, can be directly measured on a helical CT, and then divided by the total estimated liver volume to calculate the percentage of the future liver remnant. If the future liver remnant is estimated to be too small

A

B FIG. 30-50. A . CT image of a patient with right lobe and medial left lobe (segment IV) involvement by colorectal cancer liver metastases. An extended hepatic resection would be necessary to surgically excise all of the malignant disease; however, the lateral segment of the left lobe comprises less than 20% of the total hepatic volume, and the risk of postoperative liver failure would be excessive. B . CT scan from the same patient following portal vein embolization 4 weeks prior to this image being obtained. There has been significant compensatory hypertrophy of the left lateral segment, which on volumetric CT analysis now comprises between 25 and 30 percent of the total hepatic volume. The metallic coils used to embolize portal vein branches to the right lobe of the liver and the medial segment of the left lobe of the liver are clearly evident.

when also considering the presence or absence of chronic liver disease, PVE may be considered to increase the size of the future liver remnant.

Approach for Portal Vein Embolization A percutaneous transhepatic approach has become the standard technique for PVE.141 The principal advantage of this technique is that it allows direct access to the portal venous branches of the lobe and segments to be embolized via an ipsilateral approach. This

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or more commonly will develop intrahepatic or extrahepatic progression of their disease in the interval between PVE and the planned resection (see Table 30-10). Almost 250 reported extended liver resections have been performed following PVE136,139,141–148 (see Table 30-10). Perioperative mortality rates range from 0 to 7%, with no significantly higher mortality rate in cirrhotic compared to noncirrhotic patients. The reported complication rate of more than 15% following extended hepatic resection in patients who first underwent PVE is equivalent or better than most reports describing complication rates following this type of procedure without preoperative PVE. Unfortunately, few of the studies report long-term outcome and survival data. In a small series of 13 HCC patients treated with PVE followed by extended hepatectomy, the 1- and 2-year survival rates were 69% and 40%, respectively.147 In a study of 41 patients, most with colorectal cancer liver metastases, who underwent extended hepatic resection following PVE, the overall 5-year survival rate was 31%.148 In another series of 19 patients with colorectal cancer liver metastases, the 5-year actuarial survival rate after extended hepatic resection following PVE was 40%, which compared favorably to the 38% 5-year actuarial survival rate following resection in a patient cohort with a similar extent of resection without PVE.139 These promising early results suggest that PVE, when successful in increasing the volume of the future liver remnant, can increase the number of patients who can undergo a successful and safe extended hepatic resection with the goal of improving their long-term survival.149

technique minimizes the risk of thrombosis of the main trunk of the portal vein and vascular injury to the portal venous branches supplying the future liver remnant. The side effects are minor and transient and include pain from the transhepatic access site and lowgrade fever. It is important to embolize not only the main right portal vein, but also the portal venous branches to segment IV if an extended right hepatic lobectomy is planned.141 Systematic embolization of segment IV branches is imperative for two reasons. First, all segments of the liver-bearing tumor are embolized to minimize the risk of accelerated tumor growth. Accelerated tumor growth has been reported when incomplete right trisectoral embolization has been performed.142 Second, embolization of segment IV portal vein branches in addition to the main right portal vein may contribute to better hypertrophy of segments I, II, and III prior to the extended right hepatic lobectomy.

Results After Portal Vein Embolization Preoperative PVE has been used to treat primary liver malignancies, including HCC and cholangiocarcinoma, and metastatic liver tumors, particularly colorectal cancer metastases. Studies that report outcome after PVE indicate that the predicted future liver remnant volume increased from 19 to 36% of total liver volume pre-embolization to 31 to 59% postembolization.136,139,141–148 Complications are rare (0 to 10%) and there were no reported deaths after PVE (Table 30-10). Not all patients who undergo PVE undergo surgery, because some patients fail to develop adequate hypertrophy,

Table 30-10 Changes in Future Liver Remnant (FLR) Volume and Complications of Embolization and Resection Following Portal Vein Embolization (PVE) Year of No. of Study Patients Cancer Type

Mean % Increase in FLR Volume After PVE

Percentage of Embolized Patients Who Came to Major PVE Resection Complicatios

Major Perioperative Complications (Other Than Death)

30-Day Operative Deaths

1991

54

14

85

0

3 abscess, 1 pneumonia

1 (cholangitis)

1993

10

12

90

1993

20

10

NR

1 required re-embolization 1 transient hemobilia

1994

12

31 HCC, 12 CAC, 8 metastatic, 3 other CRC, HCC, CAC, 2 other GB, hilar CAC, HCC Hilar CAC

8

100

0

1995

4

Hilar CAC

10

NR

0

1995 1996

19 31

68 77

NR 1 flushing(w/carcinoid) 1 ATN, 1 bile leak

1997

7

14 GB, 5 CAC 11 22 CRC, 1 HCC, 1 13 CAC, 5 other HCC 27

100

0

1997 1999

13 84

11 10

100 79

0 2 SBO, 1 reoperation (for SBO)

1999

49

12

84

0

2000

12

10

58

2000

30

HCC 51 hilar CAC, 22 GB, 7 mets, 5 HCC, 1 benign 27 CRC, 4 HCC, 10 other 6 CRC, 2 CAC, 1 GB, 3 HCC 30 CRC

11

63

NR 1 abscess, 1 pancreatic leak 1 transient liver insufficiency

1 bile leak, 1 abscess, 2 liver insufficiency 5 prolonged jaundice

0 0 NR 2 PV thrombosis MOF and pneumonia 0 2 liver failure 1 bleeding after liver failure

2 bile leaks, 1 abscess, 1 peritonitis 2 GI anastomotic leaks 0 1 ascites and wound 0 breakdown 1 (hepatic artery injury, 1 technical; unrelated to 0 (1 death at 45 days) septic liver necrosis) PVE, 2 biliary fistulae

ATN = acute tubular necrosis; CAC = cholangiocarcinoma; CRC = colorectal carcinoma liver metastases; GB = gallbladder carcinoma; GI = gastrointestinal; HCC = hepatocellular carcinoma; met = metastases; MOF = multiorgan failure; NR = not reported; PV = portal vein; SBO = small bowel obstruction. source: Adapted and used with permission from Alvarez Perez et al.95

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FIG. 30-51. A schematic diagram demonstrating a patient undergoing radiofrequency (RF) ablation of a malignant liver tumor (top half of illustration). The multiple array RF needle electrode is inserted into the liver tumor with the intent of producing complete coagulative necrosis of the tumor and a surrounding zone of nonmalignant hepatic parenchyma. The RF needle electrode and grounding pads from the patient are attached to a radiofrequency generator. The lower portion of the diagram shows the ionic agitation that occurs around the multiple array RF needle electrode when alternating current from the RF generator is applied. Ionic agitation produces frictional heating in the tissue, resulting in coagulative necrosis of tissue around the electrode.

Radiofrequency Ablation Background and Basics of Radiofrequency Tissue Ablation The use of radiofrequency (RF) energy to produce thermal tissue destruction has been the focus of increasing research and practice over the past several years. During the application of RF energy, a high-frequency alternating current moves from the tip of an electrode into the tissue surrounding that electrode. As the ions within the tissue attempt to follow the change in the direction of the alternating current, their movement results in frictional heating of the tissue (Fig. 30-51). As the temperature within the tissue becomes elevated beyond 60˚C, cells begin to die, resulting in a region of necrosis surrounding the electrode.150

An RF needle electrode is advanced into the liver tumor to be treated via either a percutaneous, laparoscopic, or open (laparotomy) route. Using transcutaneous or intraoperative ultrasonography to guide placement, the needle electrode is advanced to the targeted area of the tumor, and then the individual wires or tines of the electrode are deployed into the tissues. Once the tines have been deployed, the needle electrode is attached to a RF generator and two dispersive electrodes (return or grounding pads) are placed on the patient, one on each thigh (see Fig. 30-51). The RF energy is then applied following an established treatment algorithm to create a sphere of cellular necrosis.151 Tumors less than 2.5 cm in their greatest dimension can be ablated with the placement of a needle electrode with an array diameter of 3.5 to 4.0 cm when the electrode is positioned in the center of the tumor (Fig. 30-52). Tumors

FIG. 30-52. The upper left illustration represents an intraoperative ultrasound probe placed on the surface of the liver to visualize small malignant tumors deep within the hepatic parenchyma. Intraoperative ultrasonography is used to guide placement of the RF needle electrode into the tumor. Once the needle is placed in the appropriate position within the tumor, the multiple array secondary electrodes are deployed from the needle tip (upper right inset illustration). When currently available RF generators and multiple array needle electrodes are used to treat a tumor nodule 2 cm in diameter or smaller, a single placement of the multiple array electrode is usually sufficient to produce a 4- to 5-cm diameter zone of coagulative necrosis to completely destroy the tumor and a surrounding zone of normal hepatic parenchyma (lower inset illustration).

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FIG. 30-53. Use of a multiple array RF needle electrode to treat a 3-cm diameter malignant liver tumor. The left side illustration demonstrates the use of a needle electrode with a multiple array diameter of 4 cm. The RF needle is first guided into the deepest portion of the tumor, and the multiple array is deployed at the interface of the posterior aspect of the tumor and normal hepatic parenchyma (area 1). This area is treated with RF energy until coagulative necrosis of the tumor and surrounding liver is complete. The multiple array is then retracted into the needle tip and the tip is withdrawn approximately 1.5 cm. The multiple array is again deployed to treat the more superficial interface of tumor and normal parenchyma (area 2). The central illustration shows that an ideal ablation destroys not only the tumor, but a 1-cm margin of surrounding hepatic parenchyma to ensure destruction of any microscopic extension of the tumor mass. The illustration on the right side of the figure shows an idealized superior view looking directly down on the tumor, again indicating the needle track placement centrally into the tumor with the multiple array tines radiating out through the tumor into the surrounding hepatic parenchyma to produce thermal ablation of the tumor and a 1-cm zone of surrounding hepatic parenchyma.

larger than 2.5 cm require more than one deployment of the needle electrode. For larger tumors, multiple placements and deployments of the electrode array may be necessary to completely destroy the tumor (Figs. 30-53 and 30-54). Treatment is planned such that the zones of coagulative necrosis overlap to ensure complete destruction of the tumor. Typically, the array is first placed at the most posterior

interface between the tumor and nondiseased liver parenchyma, and then the needle is repositioned and the array is redeployed anteriorly at 2.0- to 2.5-cm intervals within the tissue. In order to mimic a surgical margin in these unresectable tumors, the needle electrode is used to produce a thermal lesion that incorporates not only the tumor, but also nonmalignant liver parenchyma in a zone 1 cm wide

FIG. 30-54. A schematic illustration of a 5-cm diameter malignant tumor in the right lobe of the liver. The upper illustration shows the tumor in relation to the portal venous and hepatic arterial inflow blood supply to the tumor and the surrounding hepatic parenchyma. The inset illustration is a sagittal view showing the multiple overlapping cylinders of RF-induced thermal ablation that must be created to assure complete destruction of the tumor and a surrounding zone of normal hepatic parenchyma. The first areas treated are the more medial aspects of the tumor ( A and B , far right illustration superior view) to destroy this region of the tumor and its inflow blood supply. The needle electrode is placed sequentially at the margin of the tumor in the normal parenchyma so that part of the secondary multiple array is opened within the tumor and part is in the surrounding hepatic parenchyma. As demonstrated in the central inset illustration, the needle is first placed at the posterior interface of tumor and normal parenchyma (area 1). After this area has been completely treated, the array is retracted and the needle is pulled back to area 2, and the array is deployed and treatment performed. Finally, the more anterior or superficial interface between tumor and parenchyma is treated (area 3) to produce a cylindrical zone of coagulative necrosis. The far right illustration shows an idealized view looking directly down on the tumor to emphasize the RF treatment planning. Overlapping cylinders of thermal ablation are created to destroy the entire tumor and a 1-cm zone of surrounding hepatic parenchyma. Included is the sequence of needle electrode placements ( A through E ) to first treat ( A , B ) the aspects of the tumor adjacent to its inflow blood supply.

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A

B FIG. 30-55. A . A CT scan of a patient demonstrating a metastatic liver tumor in the right lobe of the liver. This is one of six metastatic hepatic lesions identified. The patient underwent resection of tumors in the left lobe of the liver and RFA of tumors in the right lobe. B . CT scan performed 6 months after RFA of the tumor in the right lobe of the liver. The radiofrequency cavitary lesion is larger than the original treated tumor. Treatment is planned to destroy the entire tumor and a surrounding zone of normal parenchyma to reduce the probability of local recurrence.

surrounding the tumor. Tumors in proximity to major blood vessels also may require additional probe deployment and duration of RFA, as these structures can act as heat sinks. CT scans performed after RFA of primary or metastatic liver tumors initially demonstrate a cystic-density lesion larger than the original tumor; the size of this cystic area decreases slightly over time (Fig. 30-55).

Indications for Radiofrequency Ablation of Liver Tumors RF energy has been used to produce coagulative necrosis in hepatic malignancies in patients who did not meet the criteria for resectability of HCC and metastatic liver tumors, and yet were candidates for a liver-directed procedure based on the presence of disease confined to the liver.151,152 The selection of patients to be treated with RFA is based on rational principles and goals. Any local therapy for malignant hepatic tumors, be it surgical resection, RFA, or some other tumor ablative technique, is generally performed with curative intent; however, a significant proportion of patients will

subsequently develop hepatic or extrahepatic recurrence from their coexistent micrometastatic disease. Occasionally, patients with tumor types usually associated with disseminated, systemic metastatic disease, such as breast or renal cancer, may be considered for RFA if they have been treated with at least 6 months of effective systemic chemotherapy, and have only liver metastasis. This latter group of patients is a small, highly selected subset from which a few patients will derive long-term survival benefit from aggressive liver-directed therapy.153 Thus RFA should be performed only in patients with no preoperative or intraoperative evidence of extrahepatic disease, and only for tumor histologies with a reasonable probability of disease metastatic only to the liver. The notable exception to considering RFA in patients with low-volume extrahepatic disease and multiple liver metastases is the subgroup of patients with functional endocrine syndromes from neuroendocrine tumor liver metastases, as some patients can survive years with their disease. The goal of RFA in this group is to perform a safe, palliative, rather than curative, treatment. RFA can be used to treat patients with a solitary hepatic tumor in a location that precludes a margin-negative hepatic resection, such as a tumor nestled between the inferior vena cava and the entry of the three hepatic veins into the liver (Fig. 30-56). The only area of the liver to avoid when treating a tumor with RFA is the hilar plate where the portal vein and hepatic arterial branches enter the liver. While these blood vessels can tolerate the heat associated with the RFA treatment, the large bile ducts coursing with them do not, and biliary fistulae or strictures are likely to occur. RFA-induced biliary injury can be minimized by excluding patients with tumors involving the perihilar region. Lastly, RFA is ideally suited to treat small HCCs in cirrhotic patients who may not be candidates for resection based on the severity of their liver dysfunction.152 With the exception of the previously noted group of patients with functional neuroendocrine tumor liver metastases, candidates for RFA should have primary or metastatic liver tumors with no clinically evident extrahepatic disease. Given the limitations of currently available RFA equipment, RF treatment for tumors greater than 5.0 cm in diameter must be applied judiciously, if at all. The local recurrence rate in larger tumors is much higher due to incomplete coagulative necrosis of malignant cells near the tumor periphery.151,152 When considering patients for a combined approach of liver resection of large tumors and RFA of smaller lesions in the opposite lobe, standard surgical considerations apply. Thus an adequate volume of perfused, functional hepatic parenchyma must remain to avoid postoperative liver failure. The volume of liver that must remain varies from patient to patient, depending on the presence of normal liver versus diseased liver related to chronic hepatitis viral infection, ethanol abuse, or some other cause of chronic hepatic inflammation leading to cirrhosis. RFA does not replace standard hepatic resection in patients with resectable disease. In contrast, RFA expands the population of patients who may be treated with aggressive liver-directed therapy in attempts to improve survival, quality of life, or palliation. Some patients heretofore not candidates for surgical therapy because of the presence of bilobar liver tumors now can be treated with a combination of liver resection and RFA.

Radiofrequency Ablation of Primary Liver Tumors The use of RFA to treat primary liver tumors was recently reported.152 The HCC tumor size treated with RFA in this patient population ranged from 1 to 7 cm in greatest dimension.153 The patients who underwent RFA of HCC nodules less than 2 cm in diameter had either small satellite tumors treated near a larger tumor

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1

2

A

B

C FIG. 30-56. A . Illustration of a malignant hepatic tumor abutting the inferior vena cava (IVC) and nestled under the right, middle, and left hepatic veins (RHV, MHV, and LHV). View (1) demonstrates the sagittal view of the tumor lying on the IVC and abutting a hepatic vein. Multiple insertions of the RF ablation needle electrode are required, with the secondary multiple array opened just outside the IVC first, and then sequentially withdrawn to treat the more anterior aspects of tumor. View (2) shows the axial view with lines indicating the multiple placements of the RF needle electrode needed to produce thermal ablation of the entire tumor and a surrounding zone of nondiseased hepatic parenchyma. Blood flow in the IVC and hepatic veins prevents thermal destruction or thrombosis of these major vessels. B . CT scan of a malignant liver tumor abutting the IVC and hepatic veins. C . CT scan 6 months after RFA shows no evidence of viable tumor and patent right and middle hepatic veins. The radiofrequency cavitary lesion is larger than the original tumor.

or multifocal small tumors involving more than one couinaud segment. As the size of the tumor increased, the number of deployments of the multiple array needle electrode and the total time of applying RF energy increased. Primary liver tumors tend to be highly vascular, therefore a vascular heat sink phenomenon may contribute to the extended ablation times. All 110 HCC patients in this study were followed for a minimum of 12 months after RFA; the median follow-up period was 19 months.152 Percutaneous or intraoperative RFA was performed in 76 (69%) and 34 patients (31%), respectively, and a total of 149

discrete HCC tumor nodules were treated with RFA. The median diameter of tumors treated percutaneously (2.8 cm) was smaller than lesions treated during laparotomy (4.6 cm). Local tumor recurrence at the RFA site developed in four patients (3.6%), all with tumors greater than 4.0 cm in diameter; all four subsequently developed recurrent HCC in other areas of the liver. New liver tumors or extrahepatic metastases developed in 50 patients (45.5%), but 56 patients (50.9%) had no evidence of recurrence. Clearly, a longer follow-up period is required to establish long-term, disease-free, and overall survival rates.

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Procedure-related complications were minimal in patients with HCC. There were no treatment-related deaths, but complications developed in 12.7% of the HCC patients.152 These complications included symptomatic pleural effusion, fever, pain, subcutaneous hematoma, subcapsular liver hematoma, and ventricular fibrillation. In addition, one patient with Child class B cirrhosis developed ascites, and another class B cirrhotic patient developed bleeding in the ablated tumor 4 days after RFA, requiring hepatic arterial embolization and transfusion of two units of packed red blood cells. All patient events resolved with appropriate clinical management within 1 week following the RFA procedure, with the exception of the development of ascites, which resolved with the use of diuretics within 3 weeks of the RFA treatment. Development of thermal injury to adjacent organs or structures, hepatic insufficiency, renal insufficiency, or coagulopathy following the application of RF energy to the target tumors was not reported for any of the patients. The overall complication rate following RFA of HCC was low, which is particularly notable because there were 50 Child class A, 31 class B, and 29 class C cirrhotic patients treated.

Radiofrequency Ablation of Metastatic Liver Tumors In these authors’ experience, the sizes of the metastatic liver tumors treated with RF energy ranged from 0.5 to 12 cm in greatest dimension.151 As was expected, as the size of the tumor increased, the number of deployments of the needle electrode and the total elapsed time of applying RF energy increased.152 For tumors in which the largest dimension was less than 1 cm, typically only one deployment was necessary, while those lesions greater than 1 cm in diameter were treated with two or more separate deployments of the needle electrode array. More than one deployment of the electrode array was used in metastatic tumors greater than 1 cm in diameter because over 70% of the metastatic tumors treated abutted a major intrahepatic blood vessel; additional RFA near the vessel was performed to ensure complete killing of tumor cells. Procedure-related complications were infrequent in patients with metastatic liver tumors. A few of the sites (10%) of intraoperative RFA expressed bleeding when the needle was withdrawn from the needle electrode track, but in all cases this was minimal (less than 5 mL) and controlled easily with electrocauterization of the puncture site at the surface of the liver. Complications following RFA arose in less than 10% of the patients. The complications included a single intrahepatic abscess, fever, pain, two biliary fistulae, and perihepatic abscess in an area of liver resection in two patients. All events resolved with appropriate clinical management within 1 month following the procedure. Thermal injury to adjacent organs or tissues, hepatic insufficiency, renal insufficiency, or coagulopathy following RFA of the hepatic metastases was not reported in any of the patients. Local recurrence or persistence of metastatic tumors at the site of the RFA occurred in approximately 7% of the patients, and over 80% of the local recurrences developed in tumors more than 5 cm in diameter. All regions of recurrence or persistence were at the periphery of the necrotic tissue of the ablated tumors (Fig. 30-57). No recurrence or persistence was noted within the center of the thermal lesions produced by RFA. New occurrences of additional hepatic or extrahepatic metastases were found in 46% of patients within 18 months post-RFA. The use of a combination of regional and systemic chemotherapy after RFA of colorectal cancer liver metastases to reduce recurrence and improve survival is currently under study by the authors. In another recent report, the results of 109 patients with 172 metastatic hepatic lesions who underwent percutaneous RFA were described.154 The median follow-up period was 3 years (range 5

FIG. 30-57. A CT scan performed 6 months after RF ablation of a hepatocellular carcinoma. An area of contrast-enhancing ingrowth of tissue into the cavity represents incomplete thermal ablation and local recurrence.

to 52 months), and local control was achieved in 121 (70%) of the lesions, but local recurrence developed in 51 (30%). Of these 51 lesions, 24 had repeat RFA and 11 (45%) achieved local control. A significant difference in local recurrence rates was observed when comparing lesions less than 3 cm (16%) to those greater than 3 cm (56%) in diameter. Median time to local recurrence was 16 months. There were no deaths and only one major complication (colonic perforation) after 162 RFA sessions (0.6%), with seven minor complications (4%). New metastases developed in 50% of the patients at a median time to recurrence of 12 months after RFA. Overall 2- and 3-year survival rates were 67 and 33%, respectively, with a median survival of 30 months.154 Thus percutaneous RFA was associated with a high incomplete treatment (local recurrence) rate due to less accurate resolution with transabdominal ultrasonography, making precise needle electrode placement to ablate the entire tumor and a surrounding rim of hepatic parenchyma more difficult. Using a laparoscopic approach with a multiprobe array monopolar RFA electrode, the results from 43 patients with 181 lesions, of which 170 were metastatic tumors, were reported.155 The size of the necrotic cavity produced by RFA was larger than the original tumor on posttreatment CT scans in all but three cases, two of which recurred locally. Local control was achieved in 88% of the lesions (72% of patients) with at least 3 months follow-up. Although the follow-up period is too short to establish long-term local and distant tumor recurrence rates, several predictors of local RFA treatment failure were identified. These included: (1) an ablation lesion size less than original tumor size (suggesting incomplete RFA) on posttreatment CT scans, (2) adenocarcinoma or sarcoma metastases (as compared to neuroendocrine metastases or HCC), (3) tumor size greater than 3 cm, and (4) laparoscopic ultrasound evidence of gross vascular invasion by tumor.155 In a larger series, 231 tumors in 84 patients were treated with 91 RFA procedures.156 The majority of patients had metastatic lesions (213 lesions in 73 patients), and 51 of the 91 treatments were with RFA alone. The other 40 treatments included RFA combined with surgical resection, cryoablation, and/or hepatic artery infusion of chemotherapy. Of the 91 treatments, 39 patients underwent RFA at laparotomy, 27 during laparoscopy, and 25 were treated percutaneously. Tumors treated with RFA ranged in size from 0.3 to 9.0 cm. There were seven major complications (8%), resulting in

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three deaths (4%). At a median follow-up period of 9 months (range 1 to 27 months), 15 patients (18%) had developed a local recurrence. Of the remaining 69 patients, 34 were alive without disease, 14 were alive with new metastatic disease, and 21 had died from their disease; new hepatic tumors or extrahepatic disease had developed in 35 patients. Although this study is challenging to interpret due to the use of multiple therapies and the combination of primary and metastatic liver lesions in the analyses, a few points are worth highlighting. In agreement with other reports, recurrence rates were related to the original size of the tumor. The mean diameter of lesions that developed a local recurrence (4.1 cm) was significantly larger than the mean diameter of those that did not (2.8 cm). However, the likelihood of recurrence was not related to the numbers of lesions ablated, colorectal versus noncolorectal metastases, or RFA treatment approach (laparotomy, laparoscopy, or percutaneously). New hepatic tumors or extrahepatic disease developed in 42% of the patients, a number similar to other reports. The authors also noted that the use of intraoperative ultrasound (either open or laparoscopic) detected additional intrahepatic tumors that were subsequently ablated in 25 of 66 patients (38%) that were not evident on preoperative imaging, suggesting a major advantage for open or laparoscopic RFA combined with intraoperative ultrasound over the percutaneous approach.156 Neuroendocrine tumors metastatic to the liver often produce symptoms secondary to excessive hormone production and release. Although only a minority of patients with neuroendocrine liver metastases may be curable by surgical techniques, significant symptomatic relief can be obtained by debulking, which may include resection combined with RFA, or RFA alone. One group reported 18 patients with 115 neuroendocrine tumors (carcinoid, islet cell, or medullary thyroid cancers) treated with RFA.157 The mean lesion size was 3.2 cm (range 1.3 to 10.0 cm), and the average number of lesions ablated per patient was six (range 1 to 14). There were two complications consisting of atrial fibrillation in one patient and upper GI bleeding in another. Fifteen patients (83%) with 100 lesions were followed for a mean of 12.1 months (range 3 to 35 months). Local recurrence in tumors treated with RFA was detected in six lesions (6%) in three of these 15 patients (20%); three patients died of progressive metastatic disease during follow-up. While the exact number was not indicated, the authors reported that most patients had significant improvement in hormone-related symptoms following RFA.157

Interstitial Laser Hyperthermic Ablation Direct thermal destruction of hepatic tumors using laser energy is known by several acronyms: LTA (laser thermal ablation), ILT (interstitial laser thermotherapy), ILP (interstitial laser photocoagulation), and LITT (laser-induced interstitial thermotherapy). These acronyms and phrases all describe the same type of thermal treatment, and because LITT is the most common acronym that appears in the medical literature, it will be used throughout the remainder of this section.

Background and Principles of Laser-Induced Interstitial Thermotherapy As described by the name of this thermal treatment modality, LITT requires placement of a laser fiber or fibers directly into the tumor or tissue to be treated. Thus LITT is a type of contact mode laser therapy. While the mechanism of action is different than that of RFA, LITT produces lethal thermal injury to tumor cells in an identical fashion. Prolonged heating of tumor cells to 45 to 55◦ C leads to cell death, while short exposure of cells to temperatures that

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exceed 60◦ C causes irreversible cell damage and death from protein denaturation, inhibition of protein synthesis, breaking of chemical bonds in DNA and RNA molecules, and loss of integrity in lipid bilayers. Application of LITT at low power produces a progressively enlarging zone of radiant and conductive tissue heating around the laser fiber or fibers. Irreversible cytotoxic effects develop in cells that are heated above 55 to 60◦ C. LITT produces local tissue heating when photons from lowintensity laser energy interact with molecular chromophores that are inherent to all mammalian cells. Photochemical effects may be accentuated by the exogenous administration of photosensitizing agents like porfimer sodium, but the presence of natural cellular chromophores is sufficient to produce exothermic photochemical reactions. Naturally occurring chromophores that interact with laser light include hemoglobin, myoglobin, bilirubin, cytochrome pigments in mitochondria, melanin, xanthophyll, rhodopsin, and lipofuscin.158 Laser light in LITT is scattered, reflected, and absorbed to varying degrees, depending on the wavelength of light, the applied laser energy, and the specific photoabsorptive properties of the tissue. The photoabsorptive characteristics of tissues can vary markedly from area to area within a tumor or normal tissue depending on tissue composition, vascularity, fibrosis, and necrosis. Natural chromophores have a strong dependence on wavelengths in the near infrared range for photochemical reactions to occur. This is fortunate because penetration depth increases with increasing wavelength of light. Thus, LITT utilizes diode lasers (wavelength 800 to 980 nm), or more frequently, neodymium:yttrium aluminum garnet (Nd:YAG) lasers (wavelength 1064 nm).158,159 Laser light at 1064 nm generated by Nd:YAG lasers has an tissue penetration depth of up to 10 to 12 mm.158 In contrast to other medical laser applications, where high-energy laser light is applied briefly to achieve rapid photocoagulation, LITT uses low-energy (3 to 20 watts) laser energy in the continuous mode applied over 2 to 20 minutes. Slow heating of tissue must be achieved by LITT to avoid carbonization and vaporization of tissue near the light-emitting portion of the laser fiber. Rapid production of a tissue coagulum from carbonization reduces optical penetration into the tissue and severely limits expansion of the zone of heated tissue with temperatures sufficient to produce lethal injury to tumor cells. In general, penetration of tumor tissue is greater than in normal tissue by approximately 33% at the 1064-nm wavelength, but rapid coagulative necrosis reduces optical penetration by up to 25% in both normal and tumor tissues.160 Similarly to RFA, transient hepatic inflow occlusion during LITT can be used to double the volume of thermal injury using single-fiber systems, and can produce up to a fivefold increase in the volume of thermal coagulation by using a four-fiber system.161 Portal venous occlusion has been shown to be more important than hepatic arterial occlusion in producing this increase in the volume of thermal necrosis, suggesting that pretreatment transarterial hepatic arterial embolization associated with percutaneous LITT is less useful than laparoscopic or open surgical occlusion of both portal venous and hepatic arterial flow with a Pringle maneuver.

Results of Laser-Induced Interstitial Thermotherapy for Malignant Hepatic Tumors The majority of reports describing LITT for the treatment of liver malignancies describe a percutaneous approach for intratumoral placement of the laser fiber using ultrasonographic or MRI monitoring during therapy. There are recent reports of use of LITT via laparoscopy or open laparotomy, particularly using a multifiber beam splitting laser system, which also permits hepatic vascular

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inflow occlusion during the treatment. The disadvantage of a laparoscopic or open surgical approach is the need for general anesthesia and a longer recovery time from a more invasive procedure.158 However, the benefits may outweigh these disadvantages in patients who are undergoing treatment of multiple tumors, where the percutaneous treatment time in the MRI scanner is excessive, or if tumors are located near key vascular or biliary structures where intraoperative ultrasonographic guidance to place the laser fiber is desirable. LITT suffers from the same problem inherent in the other recently developed, thermal ablation techniques, namely a lack of long-term follow-up data to establish disease-free and overall patient survival rates. A study of 55 patients with colorectal liver metastases treated with LITT at a mean follow-up of only 10 months was reported.162 The mean number of percutaneous LITT sessions required to completely treat all detectable tumor was 2.2 sessions per patient. The mean survival at 12 months was 86%. Another group studied 104 patients, 77 with HCC and 27 with hepatic metastases, treated with ultrasound-guided percutaneous LITT with a mean follow-up period of less than 5 months.163 Complete destruction of tumor as assessed by triphasic contrast-enhanced CT scans was noted in 82% of the HCC tumors and 77% of the hepatic metastases. Three of the cirrhotic HCC patients developed liver failure after LITT, with one of these patients dying 2 months after treatment. No data were provided on any re-treatment sessions of the patients with incomplete destruction of the tumor after LITT, nor was there mention of local recurrence rates in lesions thought to be completely destroyed based on the results of the initial posttreatment imaging studies. The largest reported experience with LITT consists of 705 patients with 1981 metastatic liver tumors.164 A total of 1653 treatment sessions consisting of 7148 laser applications were required to treat the metastatic liver tumors in these patients. All treatments were performed with percutaneous insertion of the laser fiber using realtime MRI monitoring. The local tumor control rate was 98%, based on MRI evaluation 6 months after completion of all LITT treatments in the individual patients. The mean survival time for patients with unresectable colorectal liver metastases treated by LITT was 42 months, with a 3-year actuarial survival rate of 50%. In a smaller subset of patients with breast cancer liver metastases, the mean survival was 4.3 years after LITT.164 The overall complication rate in this large series was 7.5%, but the authors report that most of the complications were mild and were treated in the outpatient setting. The rate of more significant complications requiring hospitalization, interventional therapies, or prolonged treatment was 1.3%. This is consistent with other reports of complication rates of less than 2% in patients treated with LITT.159 Reported complications include pneumothorax, hemothorax, transient bile leaks, subcapsular hemorrhage or bleeding from the needle track, bradycardia, tachycardia, right upper quadrant abdominal pain, and transient hyperthermia. The major limitation of single-fiber LITT is an inability to achieve large volumes of tumor necrosis. Another disadvantage is the need to perform multiple treatment sessions in most patients. It is possible that LITT may become a more clinically useful and widely applied treatment if improvements such as multiple fiber beam splitting systems, diffuser fiber tips, pharmacologic thermosensitization, and radiologic or direct surgical occlusion of hepatic inflow are able to overcome these problems. Presently, there are inadequate data on local tumor recurrence rates and long-term survival rates after LITT to perform a rigorous assessment of its future as a durable treatment modality for hepatic malignancies.

Microwave Coagulation Therapy for Hepatic Tumors Background and Principles of Microwave Coagulation Therapy Microwave coagulation was initially developed in the early 1980s to achieve hemostasis along the plane of transection during hepatic resection.165 Microwave coagulation of tissue surfaces was slower than electrocautery units and produced deeper areas of tissue necrosis. While microwave coagulation has not been useful during hepatic resection, the extended area of tissue necrosis led to investigation of use of microwave coagulation therapy (MCT) to treat unresectable hepatic malignancies. The microwave generators developed for MCT produce microwaves with a frequency of 2450 MHz and a wavelength of 12 cm.166 Biologically, microwaves applied to living tissues produce dielectric heat by stimulation of water molecules within the tissue and cells. The rapid agitation of water molecules within cells and tissues with direct application of microwaves produces rapid frictional heating and coagulative necrosis. The microwave generators available for clinical use have an output of 70 to 90 watts. The microwave-emitting needle (14- to 22-gauge) is placed directly into the hepatic tumor to be treated, usually using ultrasonographic guidance, then is attached to the microwave generator, the generator is activated, and each area of the tumor is treated for 30 to 60 seconds at 70 to 90 watts of power. The rapid generation of heat using MCT produces 10- to 25-mm zones of coagulative necrosis after only 30 to 60 seconds. The lesions can range from spherical to elliptical in shape. The rapid development of coagulative necrosis within the tissue around the MCT needle produces a tissue coagulum that inhibits further dissipation of heat into the tissue. The small areas of coagulation produced by MCT requires that the needle be advanced at 5- to 10-mm intervals throughout the area to be treated and surrounding parenchyma to create multiple overlapping zones of coagulative necrosis. For tumors larger than 2 cm in diameter, multiple MCT needle placements are required to produce overlapping zones of coagulative necrosis in the tumor and in a surrounding rim of hepatic parenchyma. Like RFA and LITT, MCT can be performed percutaneously using ultrasound or CT guidance for needle placement, or can be performed laparoscopically or during an open surgical procedure using intraoperative ultrasound guidance to place the MCT needle.

Results of Microwave Coagulation Therapy for Treatment of Malignant Hepatic Tumors The overwhelming majority of reports describing MCT to treat hepatic malignancies come from Japan, where this technique was first used in 1988. There, MCT has been used principally to treat cirrhotic HCC patients. Most of the patients treated with MCT, even those with a solitary tumor less than 3 cm in size, were not candidates for resection because of the severity of their cirrhosis. A study of 19 patients with unresectable HCC reported that MCT was performed during laparotomy in 12 patients, laparoscopically in five patients, and using a thoracotomy approach in two patients with tumors at the dome of the liver.167 A solitary HCC tumor was treated in 13 patients, while the remaining six patients had between two and five HCC tumors treated with MCT. MCT was performed to palliate symptoms from a large tumor in six of the 19 patients who had additional intrahepatic or extrahepatic metastases. The mean size of the tumors treated with MCT was 21 mm (range 5 to 90 mm), and the mean duration of operation was 4.7 hours (range 1.8 to 7.0 hours).

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The reproducible and reliable zone of complete coagulative necrosis around the MCT needle electrode is only 10 mm; thus the mean number of electrode insertions to treat the HCC tumors was 46 (range 10 to 135). The authors report that the follow-up period in these patients ranged from 4 to 64 months; there were two patients treated with curative intent who were alive 47 and 64 months, respectively, after MCT, with no evidence of recurrent or new metastatic HCC. In the entire group of 19 patients, six patients had died of recurrent HCC or progressive liver failure, 10 were alive without radiographic evidence of recurrent HCC, and three were alive with evidence of new HCC metastases.167 The authors reported that there was no evidence of local recurrence in 28 of the 31 nodules (90%) treated with MCT. However, it is difficult to assess the true local recurrence rate, because most of the patients were treated with hepatic arterial chemoembolization after MCT. A recent report evaluated the risk factors for distant recurrence of HCC after treatment with MCT or RFA.168 A total of 92 patients with HCC tumors less than 3 cm in diameter were treated with MCT (68 patients) or RFA (16 patients). All patients were treated percutaneously or laparoscopically. This was a nonrandomized study, so MCT or RFA was selected as a treatment option based on the preference of the treating surgeon. Eighty-four patients were followed for 12 to 44 months after treatment (median follow-up period of 22 months); the remaining eight patients died before 12 months because of hepatic failure (five patients), HCC progression (two patients), or pneumonia (one patient). In the 84 evaluable patients, the 1-year survival rate was 99% and the 3-year survival rate was 78%. During the follow-up period, distant recurrence of HCC was observed in 22 patients (26%). There is no comment on local recurrence rates after MCT or RFA in any of these patients. The only variables found to be significant in predicting a higher risk for the development of distant metastatic HCC after MCT or RFA were the treatment of more than one HCC nodule, or the presence of chronic hepatitis C infection as the underlying etiology of chronic liver disease.168 There is a striking paucity of data on local recurrence rates and complications following MCT to treat HCC or other malignant liver tumors. Some authors mention that MCT should not be performed near the hepatic hilum, where major bile ducts and blood vessels are located, or near any major hepatic blood vessels, suggesting that there is experience with vascular and biliary complications related to treatment of tumors in these locations. It is unlikely that MCT will be widely applied to treat patients with unresectable malignant hepatic tumors unless modifications in equipment and treatment algorithms occur to produce larger zones of coagulative necrosis around the MCT needle.

Adjuvant Treatment of Liver Malignancies There is no accepted or clinically superior single combination of agents used as postresection adjuvant therapy for colorectal metastases or HCC. A nonrandomized study of 57 patients with colorectal cancer liver metastases who underwent liver resection examined 31 patients who were treated with adjuvant hepatic arterial infusion consisting of 5-fluorouracil (5-FU), doxorubicin, and mitomycin C, while 26 patients were treated with resection alone.169 The surgical complication rate was not mentioned, nor was there information provided on the incidence or types of toxicities associated with the adjuvant treatment. The 3- and 5-year survival rates in the 26 patients who did not receive adjuvant therapy were 35 and 12%, respectively, compared to 57 and 57%, respectively, for the 31 patients who received adjuvant regional chemotherapy.

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Another nonrandomized, prospective study of 110 patients who underwent hepatic resection for colorectal liver metastases included 60 patients who received adjuvant hepatic arterial chemotherapy.170 The surgical resection was not curative in 26% of patients. Individuals were treated with four different adjuvant chemotherapy regimens consisting of floxuridine (FUDR) alone, FUDR and folinic acid, or 5-FU and folinic acid. There was no difference in the postoperative morbidity or mortality rates comparing patients who did or did not undergo placement of a hepatic artery infusion pump at the time of liver resection. At least five cycles of adjuvant chemotherapy were administered in 48 of the 60 patients (80%). The remaining patients did not complete adjuvant therapy because of problems with occlusion, dislodgment, or leakage from the hepatic arterial catheter. The 3- and 5-year survival rates for patients treated with adjuvant hepatic arterial chemotherapy following curative surgery were 60% and 41%, respectively. These survival rates were significantly better compared to patients treated with curative surgery alone (3- and 5year survival rates of 43 and 25%, respectively). The median survival time in patients treated with curative hepatic resection and adjuvant hepatic arterial chemotherapy was 54 months. The most common toxicity related to regional chemotherapy was stomatitis in patients who received 5-FU, while transient increases in serum hepatic enzyme levels was the most common occurrence noted after administration of FUDR. Of the 33 patients who received adjuvant hepatic arterial infusion with FUDR, two (6%) developed biliary sclerosis. A retrospective, nonrandomized study of 174 patients who underwent resection of colorectal liver metastases compared the outcome of the 78 patients who received adjuvant hepatic arterial infusion chemotherapy to 30 who had adjuvant portal venous infusion chemotherapy and 66 who had no adjuvant treatment.171 The adjuvant hepatic arterial infusion or portal venous infusion chemotherapy regimen consisted of 5-FU, aclarubicin suspended in an oily contrast medium, and mitomycin C. A total of six patients (3.4%), including one in the hepatic artery infusion group, one in the portal vein infusion group, and four in the resection alone group, died within 60 days of hepatic resection secondary to hepatic failure. The toxicity of adjuvant chemotherapy consisted of nausea, emesis, and diarrhea, which occurred in 59% of the patients receiving hepatic arterial infusion chemotherapy and in 77% of the patients receiving portal venous infusion chemotherapy. Most of the patients required dose reduction of their chemotherapy related to hematologic toxicity, but no patient developed biliary sclerosis or drug-induced hepatitis. The actuarial 5-year, disease-free survival rates for the hepatic arterial infusion, portal venous infusion, and resection-alone groups were 35%, 13%, and 9%, respectively. The corresponding overall 5-year survival rates were 40%, 17%, and 20%, respectively. The disease-free and overall survival rate was significantly better for the group of patients treated with hepatic arterial infusion chemotherapy compared to patients treated with portal venous infusion chemotherapy or surgery alone. Patients treated with hepatic arterial infusion chemotherapy had a significantly lower rate of recurrence of disease in the liver, while portal venous infusion chemotherapy did not reduce the incidence of hepatic recurrence compared to patients treated with surgery alone. A randomized, prospective trial from the United States assigned 156 patients undergoing resection of colorectal cancer liver metastases to one of two adjuvant treatment arms.172 Patients received either 6 monthly cycles of systemic 5-FU and folinic acid or hepatic arterial infusion chemotherapy with FUDR and dexamethasone plus systemic 5-FU, with or without folinic acid. The patients were assigned randomly at the time of liver resection to one of the two treatment arms, and were stratified according to previous systemic

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chemotherapy treatment and number of liver metastases. There was a significant improvement in actuarial overall 2-year survival and a lower rate of hepatic recurrence in the group treated with regional combined with systemic chemotherapy (86%, 2-year actuarial survival) compared to the group treated with adjuvant systemic chemotherapy alone (72%, 2-year actuarial survival). With a median follow-up period of 63 months, the median survival in the combined regional and systemic chemotherapy group was 72 months versus 59 months in the patients who received only adjuvant systemic therapy. Chemotherapy-related side effects occurred with equal frequency in the two treatment arms, but the rate of diarrhea and abnormalities in serum liver tests was higher in patients in the combined regional plus systemic chemotherapy arm. Many of the patients in the combined regional and systemic therapy arm were unable to complete the planned 6 months of adjuvant therapy because of chemotherapy-induced elevations in serum liver tests. Adjuvant therapy after resection of HCC also has been studied. A randomized, prospective trial assigned patients to a single postoperative dose of 131 I-lipiodol or no further treatment.173 Of the 43 patients recruited to the trial, 21 received a single hepatic arterial infusion of 131 I-lipiodol 6 weeks after liver resection and 22 received no adjuvant treatment. With a median follow-up period of 35 months, recurrent HCC developed in six of the 21 patients (29%) who received adjuvant 131 I-lipiodol, compared with 13 of the 22 (59%) control patients. There was a significant improvement in median disease-free survival in the treatment group (57.2 months) compared with the surgery alone group (13.6 months). Additionally, the 3-year overall survival was significantly improved in the treatment versus control group, 86.4% versus 46.3%, respectively. There was no significant toxicity related to the single postoperative intra-arterial infusion of 131 I-lipiodol. Data regarding the effect of neoadjuvant therapy for unresectable colorectal cancer recently has been published. In 701 patients initially considered unresectable and then treated with systemic 5-FU, folinic acid, and oxaliplatin, 95 (13%) achieved significant reduction in tumor size and subsequently underwent a potentially curative hepatic resection.174 The mean number of chemotherapy sessions required to achieve tumor reduction sufficient to allow resection was 10.6 over a 10-month period. There was no perioperative mortality and the postoperative complication rate was 23%. The overall 5year survival rate in these 95 patients downstaged with neoadjuvant therapy was 34%. When 5-year survival was evaluated based on the initial reason the patients were felt to have unresectable disease, it was determined that 5-year survival was 60% in patients with large tumors, 49% for tumors located near major vascular structures preventing a margin-negative resection, 34% for patients with multinodular disease, and 18% for those with evidence of extrahepatic disease at the time of presentation. Neoadjuvant and adjuvant therapy trials have indicated that an increased number of patients may be considered for resection with aggressive preoperative therapy, and the disease-free and overall survival rates of patients may be improved using adjuvant therapy after resection of colorectal cancer liver metastases and HCC. In a phase II trial at the University of Texas M.D. Anderson Cancer Center, these authors have found that adjuvant hepatic arterial infusion chemotherapy with either RFA alone or RFA combined with resection of colorectal cancer liver metastases reduced the incidence of hepatic recurrence of disease.175 The follow-up period in this cohort of patients is not yet sufficient to allow analysis of long-term survival. Entry into clinical trials of neoadjuvant and

adjuvant therapy after resection or thermal ablation of malignant liver tumors should be considered in all patients undergoing surgical treatment. Overall, the results from neoadjuvant therapy trials to downstage patients with primary or metastatic liver tumors in an attempt to convert unresectable to resectable disease indicates that only 10 to 20% of such patients will actually undergo a resection. Most patients will have disease that is too widespread or will fail to respond sufficiently to the preoperative treatment regimen to be considered for surgical treatment. Nonetheless, the survival rate in patients who do achieve significant tumor downstaging is similar to the long-term survival rates for patients who have resectable disease at the time of the initial diagnosis of their malignant liver tumors. Further investigation of multimodality neoadjuvant treatments is ongoing in an attempt to increase the proportion of patients who become resectable and to improve the overall outcome.

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70. Hui T, Rozga J, Demetriou AA: Bioartificial liver support. J HepatoBiliary-Pancreatic Surg 8:1, 2001. 71. Regev A, Reddy KR, Berho M, et al: Large cystic lesions of the liver in adults: A 15-year experience in a tertiary center. J Am Coll Surg 193:36, 2001. 72. Ammori BJ, Jenkins BL, Lim PC, et al: Surgical strategy for cystic diseases of the liver in a western hepatobiliary center. World J Surg 26:462, 2002. 73. Katkhouda N, Hurwitz M, Gugenheim J, et al: Laparoscopic management of benign solid and cystic lesions of the liver. Ann Surg 229:460, 1999. 74. Gigot JF, Metairie S, Etienne J, et al: The surgical management of congenital liver cysts. Surg Endosc 15:357, 2001. 75. Geevarghese SK, Powers T, Marsh JW, et al: Screening for cerebral aneurysm in patients with polycystic liver disease. South Med J 92:1167, 1999. 76. Johnson LB, Kuo PC, Plotkin JS: Transverse hepatectomy for symptomatic polycystic liver disease. Liver 19:526, 1999. 77. Mortele KJ, Ros PR: Cystic focal liver lesions in the adult: Differential CT and MR imaging features. Radiographics 21:895, 2001. 78. Lauffer JM, Baer HU, Maurer CA, et al: Biliary cystadenocarcinoma of the liver: The need for complete resection. Eur J Cancer 34:1845, 1998. 79. Kim K, Choi J, Park Y, et al: Biliary cystadenoma of the liver. J HepatoBiliary-Pancreatic Surg 5:348, 1998. 80. Semelka RC, Martin DR, Balci C, Lance T: Focal liver lesions: Comparison of dual-phase CT and multisequence multiplanar MR imaging including dynamic gadolinium enhancement. J Magn Reson Imag 13:397, 2001. 81. Horton KM, Bluemke DA, Hruban RH, et al: CT and MR imaging of benign hepatic and biliary tumors. Radiographics 19:431, 1999. 82. Trotter JF, Everson GT: Benign focal lesions of the liver. Clin Liver Dis 5:17, 2001. 83. Reddy KR, Kligerman S, Levi J, et al: Benign and solid tumors of the liver: Relationship to sex, age, size of tumors, and outcome. Am Surg 67:173, 2001. 84. De Carlis L, Pirotta V, Rondinara GF, et al: Hepatic adenoma and focal nodular hyperplasia: Diagnosis and criteria for treatment. Liver Transplant Surg 3:160, 1997. 85. Mortele KJ, Praet M, Van Vlierberghe H, et al: Focal nodular hyperplasia of the liver: Detection and characterization with plain and dynamic-enhanced MRI. Abdom Imag 27:700, 2002. 86. Ribeiro A, Burgart LJ, Nagorney DM, et al: Management of liver adenomatosis: Results with a conservative surgical approach. Liver Transplant Surg 4:388, 1998. 87. Charny CK, Jarnagin WR, Schwartz LH, et al: Management of 155 patients with benign liver tumours. Br J Surg 88:808, 2001. 88. Foster JH, Berman MM: The malignant transformation of liver cell adenomas. Arch Surg 129:712, 1994. 89. Descottes B, Glineur D, Lachachi F, et al: Laparoscopic liver resection of benign liver tumors. [erratum appears in Surg Endosc 17:668, 2003.] Surg Endosc 17:23, 2003. 90. Baer HU, Dennison AR, Mouton W, et al: Enucleation of giant hemangiomas of the liver. Technical and pathologic aspects of a neglected procedure. Ann Surg 216:673, 1992. 91. Gedaly R, Pomposelli JJ, Pomfret EA, et al: Cavernous hemangioma of the liver: Anatomic resection vs. enucleation. Arch Surg 134:407, 1999. 92. Terkivatan T, Vrijland WW, Den Hoed PT, et al: Size of lesion is not a criterion for resection during management of giant liver haemangioma. Br J Surg 89:1240, 2002. 93. Petri A, Hohn J, Hodi Z, et al: Pyogenic liver abscess—20 years’ experience. Comparison of results of treatment in two periods. Langenbecks Arch Surg 387:27, 2002. 94. Lee KT, Wong SR, Sheen PC: Pyogenic liver abscess: An audit of 10 years’ experience and analysis of risk factors. Dig Surg 18:459, 2001.

95. Alvarez Perez JA, Gonzalez JJ, Baldonedo RF, et al: Clinical course, treatment, and multivariate analysis of risk factors for pyogenic liver abscess. Am J Surg 181:177, 2001. 96. Lam YH, Wong SK, Lee DW, et al: ERCP and pyogenic liver abscess. Gastrointest Endosc 50:340, 1999. 97. Ch Yu S, Hg Lo R, Kan PS, et al: Pyogenic liver abscess: Treatment with needle aspiration. Clin Radiol 52:912, 1997. 98. Alvarez JA, Gonzalez JJ, Baldonedo RF, et al: Single and multiple pyogenic liver abscesses: Etiology, clinical course, and outcome. Dig Surg 18:283, 2001. 99. Sayek I, Onat D: Diagnosis and treatment of uncomplicated hydatid cyst of the liver. World J Surg 25:21, 2001. 100. Khuroo MS, Wani NA, Javid G, et al: Percutaneous drainage compared with surgery for hepatic hydatid cysts. N Engl J Med 337:881, 1997. 101. Sielaff TD, Taylor B, Langer B: Recurrence of hydatid disease. World J Surg 25:83, 2001. 102. Yorganci K, Sayek I: Surgical treatment of hydatid cysts of the liver in the era of percutaneous treatment. Am J Surg 184:63, 2002. 103. Hughes MA, Petri WA Jr.: Amebic liver abscess. Infect Dis Clin North Am 14:565, 2000. 104. Akgun Y, Tacyildiz IH, Celik Y: Amebic liver abscess: Changing trends over 20 years. World J Surg 23:102, 1999. 105. McGarr PL, Madiba TE, Thomson SR, et al: Amoebic liver abscess— results of a conservative management policy. South Afr Med J 93:132, 2003. 106. Fortner JG, Blumgart LH: A historic perspective of liver surgery for tumors at the end of the millennium. J Am Coll Surg 193:210, 2001. 107. Elliot JW: Surgical treatment of tumor of the liver with report of a case. Ann Surg 26:83, 1897. 108. Couinaud C: Etudes anatomiques et chirurgales. Paris: Mason, 1957, p 1. 109. Curley SA: Surgical management of hepatocellular carcinoma, in Curley SA (ed): Liver Cancer. M.D. Anderson Solid Tumor Oncology Series. New York: Springer-Verlag, 1998, p 28. 110. Lau H, Man K, Fan ST, et al: Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg 84:1255, 1997. 111. Kobayashi T, Kubota K, Imamura H, et al: Hepatic phenylalanine metabolism measured by the [13C]phenylalanine breath test. Eur J Clin Invest 31:356, 2001. 112. Meyer-Wyss B, Renner E, Luo H, et al: Assessment of lidocaine metabolite formation in comparison with other quantitative liver function tests. J Hepatol 19:133, 1993. 113. Hamming AW, Gallinger S, Greig PD, et al: The hippurate ratio as an indicator of functional hepatic reserve for resection of hepatocellular carcinoma in cirrhotic patients. J Gastrointest Surg 5:316, 2001. 114. Hwang EH, Taki J, Shuke N, et al: Preoperative assessment of residual hepatic functional reserve using 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT. J Nucl Med 40:1644, 1999. 115. Shiomi S, Iwata Y, Sasaki N, et al: Assessment of hepatic blood flow by PET with 15O water: Correlation between per-rectal portal scintigraphy with 99Tc(m)-pertechnetate and scintigraphy with 99Tc(m)-GSA. Nucl Med Commun 21:533, 2000. 116. Di Bisceglie AM, Carithers RL Jr., Gores GJ: Hepatocellular carcinoma. Hepatology 28:1161, 1998. 117. Anthony PP: Hepatocellular carcinoma: An overview. Histopathology 39:109, 2001. 118. Weiss L, Grundmann E, Torhorst J, et al: Haematogenous metastatic patterns in colonic carcinoma: An analysis of 1541 necropsies. J Pathol 150:195, 1986. 119. Bilimoria MM, Lauwers GY, Doherty DA, et al: Underlying liver disease, not tumor factors, predicts long-term survival after resection of hepatocellular carcinoma. Arch Surg 136:528, 2001. 120. Fong Y, Cohen AM, Fortner JG, et al: Liver resection for colorectal metastases. J Clin Oncol 15:938, 1997. 121. Resection of the liver for colorectal carcinoma metastases: A

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multi-institutional study of indications for resection. Registry of Hepatic Metastases. Surgery 103:278, 1988. Minagawa M, Makuuchi M, Torzilli G, et al: Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: Long-term results. Ann Surg 231:487, 2000. Weber SM, Jarnagin WR, DeMatteo RP, et al: Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 7:643, 2000. Poon RT, Fan ST, Lo CM, et al: Improving survival results after resection of hepatocellular carcinoma: A prospective study of 377 patients over 10 years. Ann Surg 234:63, 2001. Grazi GL, Ercolani G, Pierangeli F, et al: Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value. Ann Surg 234:71, 2001. Yanaga K, Nishizaki T, Yamamoto K, et al: Simplified inflow control using stapling devices for major hepatic resection. Arch Surg 131:104, 1996. Ramacciato G, Balesh AM, Fornasari V: Vascular endostapler as aid to hepatic vein control during hepatic resections. Am J Surg 172:358, 1996. Descottes B, Lachachi F, Sodji M, et al: Early experience with laparoscopic approach for solid liver tumors: Initial 16 cases. Ann Surg 232:641, 2000. Cherqui D, Husson E, Hammoud R, et al: Laparoscopic liver resections: A feasibility study in 30 patients. Ann Surg 232:753, 2000. Tuttle TM, Curley SA, Roh MS: Repeat hepatic resection as effective treatment for recurrent colorectal liver metastases. Ann Surg Oncol 4:125, 1996. Imamura H, Kawasaki S, Miyagawa S, et al: Aggressive surgical approach to recurrent tumors after hepatectomy for metastatic spread of colorectal cancer to the liver. Surgery 127:528, 2000. Nakajima Y, Ko S, Kanamura T, et al: Repeat liver resection for hepatocellular carcinoma. J Am Coll Surg 192:339, 2001. Matsuda M, Fujii H, Kono H, et al: Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: Repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepatobiliary Pancreatic Surg 8:353, 2001. Kinoshita H, Sakai K, Hirohashi K, et al: Preoperative portal vein embolization for hepatocellular carcinoma. World J Surg 10:803, 1986. Melendez J, Ferri E, Zwillman M, et al: Extended hepatic resection: A 6-year retrospective study of risk factors for perioperative mortality. J Am Coll Surg 192:47, 2001. Vauthey JN, Chaoui A, Do KA, et al: Standardized measurement of the future liver remnant prior to extended liver resection: Methodology and clinical associations. Surgery 127:512, 2000. Abdalla EK, Barnett CC, Doherty DA, et al: Extended hepatectomy in hepatobiliary malignancies with and without preoperative portal vein embolization. Arch Surg 137:675, 2002. Kubota MK, Makuuchi M, Kusaka K, et al: Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors. Hepatology 26:1176, 1997. Azoulay D, Castaing D, Smail A, et al: Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg 231:480, 2000. Urata K, Kawasaki S, Matsunami H, et al: Calculation of child and adult standard liver volume for liver transplantation. Hepatology 21:1317, 1995. Nagino M, Kamiya J, Kanai M, et al: Right trisegment portal vein embolization for biliary tract carcinoma: Technique and clinical utility. Surgery 127:155, 2000. Elias D, De Baere T, Roche A, et al: During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma. Br J Surg 86:784, 1999. de Baere T, Roche A, Elias D, et al: Preoperative portal vein embolization for extension of hepatectomy indications. Hepatology 24:1386, 1996. Imamura H, Shimada R, Kubota M, et al: Preoperative portal vein embolization: An audit of 84 patients. Hepatology 29:1099, 1999.

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145. Shimamura T, Nakajima Y, Une Y, et al: Efficacy and safety of preoperative percutaneous transhepatic portal embolization with absolute ethanol: A clinical study. Surgery 121:135, 1997. 146. Kawasaki S, Makuuchi M, Miyagawa S, et al: Radical operation after portal embolization for tumor of hilar bile duct. J Am Coll Surg 178:480, 1994. 147. Wakabayashi H, Okada S, Maeba T, et al: Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: A preliminary report. Surg Today 27:403, 1997. 148. Elias D, Cavalcanti A, De Baere T, et al: Resultats carcinologiques a long terme des hepatectomies realisee apres embolisation portal selective. Ann Chir 53:559, 1999. 149. Abdalla EK, Hicks ME, Vauthey JN: Portal vein embolization: Rationale, technique and future prospects. Br J Surg 88:165, 2001. 150. McGahan JP, Brock JM, Tesluk H, et al: Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Intervent Radiol 3:291, 1992. 151. Curley SA, Izzo F, Delrio P, et al: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: Results in 123 patients. Ann Surg 230:1, 1999. 152. Curley SA, Izzo F, Ellis LM, et al: Radiofrequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 232:381, 2000. 153. Curley SA: Radiofrequency ablation of malignant liver tumors. Oncologist 6:14, 2001. 154. Solbiati L, Ierace T, Tonolini M, et al: Radiofrequency thermal ablation of hepatic metastases. Eur J Ultrasound 13:149, 2001. 155. Siperstein A, Garland A, Engle K, et al: Local recurrence after laparoscopic radiofrequency thermal ablation of hepatic tumors. Ann Surg Oncol 7:106, 2000. 156. Wood TF, Rose DM, Chung M, et al: Radiofrequency ablation of 231 unresectable hepatic tumors: Indications, limitations, and complications. Ann Surg Oncol 7:593, 2000. 157. Siperstein AE, Berber E: Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg 25:693, 2001. 158. Germer CT, Albrecht D, Roggan A, et al: Technology for in situ ablation by laparoscopic and image-guided interstitial laser hyperthermia. Semin Laparosc Surg 5:195, 1998. 159. Muralidharan V, Christophi C: Interstitial laser thermotherapy in the treatment of colorectal liver metastases. J Surg Oncol 76(Suppl):73, 2001. 160. Germer CT, Roggan A, Ritz JP, et al: Optical properties of native and coagulated human liver tissue and liver metastases in the near infrared range. Lasers Surg Med 23:194, 1998. 161. Sturesson C, Liu DL, Stenram U, et al: Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat. J Surg Res 71:67, 1997. 162. Gilliams AR, Brokes J, Hare C: Follow-up of patients with metastatic liver lesions treated with interstitial laser therapy. Br J Cancer 76:31, 1997. 163. Giorgio A, Tarantino L, de Stefano G, et al: Interstitial laser photocoagulation under ultrasound guidance of liver tumors: Results in 104 treated patients. Eur J Ultrasound 11:181, 2000. 164. Mack MG, Straub R, Eichler K, et al: Percutaneous MR imaging-guided laser-induced thermotherapy metastases. Abdom Imaging 26:369, 2001. 165. Tabuse K, Katsumi M, Kobayashi Y, et al: Microwave surgery: Hepatectomy using a microwave tissue coagulator. World J Surg 9:136, 1985. 166. Seki T, Wakabayashi M, Nakagawa T, et al: Ultrasonically guided percutaneous microwave coagulation therapy for small hepatocellular carcinoma. Cancer Res 74:817, 1994. 167. Sato M, Watanabe Y, Ueda S, et al: Microwave coagulation therapy for hepatocellular carcinoma. Gastroenterology 110:1507, 1996.

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168. Izumi N, Asahina Y, Noguchi O, et al: Risk factors for distant recurrence of hepatocellular carcinoma in the liver after complete coagulation by microwave or radiofrequency ablation. Cancer Res 91:949, 2001. 169. Nonami T, Takeuchi Y, Yasui M, et al: Regional adjuvant chemotherapy after partial hepatectomy for metastatic colorectal carcinoma. Semin Oncol 24:S6, 1997. 170. Lorenz M, Staib-Sebler E, Koch B, et al: The value of postoperative hepatic arterial infusion following curative liver resection. Anticancer Res 17:3825, 1997. 171. Ambiru S, Miyazaki M, Ito H, et al: Adjuvant regional chemotherapy after hepatic resection for colorectal metastases. Br J Surg 86:1025, 1999.

172. Kemeny N, Huang Y, Cohen AM, et al: Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341:2039, 1999. 173. Lau WY, Leung TW, Ho SK, et al: Adjuvant intra-arterial iodine-131labelled lipiodol for resectable hepatocellular carcinoma: A prospective randomised trial. Lancet 353:797, 1999. 174. Adam R, Avisar E, Ariche A, et al: Five-year survival following hepatic resection after neoadjuvant therapy for non-resectable colorectal liver metastases. Ann Surg Oncol 8:347, 2001. 175. Scaife CL, Curley SA, Patt Y, et al: Feasibility of adjuvant hepatic arterial infusion (HAI) of chemotherapy following radiofrequency ablation (RFA) +/– resection in patients with hepatic metastasis from colorectal cancer. Ann Surg Oncol 10:348, 2003.

CHAPTER

31

Gallbladder and the Extrahepatic Biliary System Margret ´ Oddsdottir ´ and John G. Hunter

Anatomy

Other Benign Diseases and Lesions

The Gallbladder The Bile Ducts Anomalies

Acalculous Cholecystitis Biliary Cysts Sclerosing Cholangitis Stenosis of the Sphincter of Oddi Bile Duct Strictures

Physiology Bile Formation and Composition Gallbladder Function Absorption and Secretion Motor Activity Neurohormonal Regulation Sphincter of Oddi Diagnostic Studies Blood Tests Ultrasonography Oral Cholecystography Biliary Radionuclide Scanning (HIDA Scan) Computed Tomography Percutaneous Transhepatic Cholangiography Magnetic Resonance Imaging Endoscopic Retrograde Cholangiography and Endoscopic Ultrasound Gallstone Disease Prevalence and Incidence Natural History Gallstone Formation Cholesterol Stones Pigment Stones Symptomatic Gallstones Chronic Cholecystitis Acute Cholecystitis Choledocholithiasis Cholangitis Biliary Pancreatitis Cholangiohepatitis Operative Interventions for Gallstone Disease Cholecystostomy Cholecystectomy Laparoscopic Cholecystectomy Open Cholecystectomy Intraoperative Cholangiogram or Ultrasound Choledochal Exploration Choledochal Drainage Procedures Transduodenal Sphincterotomy

Injury to the Biliary Tract The Gallbladder The Extrahepatic Bile Ducts Diagnosis Management Outcome Tumors Carcinoma of the Gallbladder Incidence Etiology Pathology Clinical Manifestations and Diagnosis Treatment Prognosis Bile Duct Carcinoma Incidence Etiology Pathology Clinical Manifestations and Diagnosis Treatment Prognosis

ANATOMY The Gallbladder The gallbladder is a pear-shaped sac, about 7 to 10 cm long with an average capacity of 30 to 50 mL. When obstructed, the gallbladder can distend markedly and contain up to 300 mL.1 The gallbladder is located in a fossa on the inferior surface of the liver that is in line with the anatomic division of the liver into right and left liver lobes. The gallbladder is divided into four anatomic areas: the fundus, the corpus (body), the infundibulum, and the neck. The fundus is the rounded, blind end that normally extends 1 to 2 cm beyond the liver’s margin. It contains most of the smooth muscles of the organ, in contrast to the body, which is the main storage area and contains most of the elastic tissue. The body extends from the fundus and tapers into the neck, a funnel-shaped area that connects with the cystic duct. The neck usually follows a gentle curve, the convexity

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b a m l c

k

d

e j h i f g n

FIG. 31-1. Anterior aspect of the biliary anatomy. a . Right hepatic duct. b. Left hepatic duct. c. Common hepatic duct. d. Portal vein. e. Hepatic artery. f . Gastroduodenal artery. g. Right gastroepiploic artery. h. Common bile duct. i . Fundus of the gallbladder. j . Body of the gallbladder. k . Infundibulum. l . Cystic duct. m. Cystic artery. n. Superior pancreaticoduodenal artery. Note the situation of the hepatic bile duct confluence anterior to the right branch of the portal vein, and the posterior course of the right hepatic artery behind the common hepatic duct.

of which may be enlarged to form the infundibulum or Hartman’s pouch. The neck lies in the deepest part of the gallbladder fossa and extends into the free portion of the hepatoduodenal ligament (Fig. 31-1). The same peritoneal lining that covers the liver covers the fundus and the inferior surface of the gallbladder. Occasionally the gallbladder has a complete peritoneal covering, and is suspended in a mesentery off the inferior surface of the liver, and rarely it is embedded deep inside the liver parenchyma (an intrahepatic gallbladder). The gallbladder is lined by a single, highly-folded, tall columnar epithelium that contains cholesterol and fat globules. The mucus secreted into the gallbladder originates in the tubuloalveolar glands found in the mucosa lining the infundibulum and neck of the gallbladder, but are absent from the body and fundus. The epithelial lining of the gallbladder is supported by a lamina propria. The muscle layer has circular longitudinal and oblique fibers, but without welldeveloped layers. The perimuscular subserosa contains connective tissue, nerves, vessels, lymphatics, and adipocytes. It is covered by the serosa except where the gallbladder is embedded in the liver. The gallbladder differs histologically from the rest of the gastrointestinal tract in that it lacks a muscularis mucosa and submucosa. The cystic artery that supplies the gallbladder is usually a branch of the right hepatic artery (>90% of the time). The course of the cystic artery may vary, but it nearly always is found within the hepatocystic triangle, the area bound by the cystic duct, common hepatic duct, and the liver margin (triangle of Calot). When the cystic artery

reaches the neck of the gallbladder, it divides into anterior and posterior divisions. Venous return is carried either through small veins that enter directly into the liver, or rarely to a large cystic vein that carries blood back to the portal vein. Gallbladder lymphatics drain into nodes at the neck of the gallbladder. Frequently, a visible lymph node overlies the insertion of the cystic artery into the gallbladder wall. The nerves of the gallbladder arise from the vagus and from sympathetic branches that pass through the celiac plexus. The preganglionic sympathetic level is T8 and T9. Impulses from the liver, gallbladder, and the bile ducts pass by means of sympathetic afferent fibers through the splanchnic nerves and mediate the pain of biliary colic. The hepatic branch of the vagus nerve supplies cholinergic fibers to the gallbladder, bile ducts, and the liver. The vagal branches also have peptide-containing nerves containing agents such as substance P, somatostatin, enkephalins, and vasoactive intestinal polypeptide (VIP).2

The Bile Ducts The extrahepatic bile ducts consist of the right and left hepatic ducts, the common hepatic duct, the cystic duct, and the common bile duct or choledochus. The common bile duct enters the second portion of the duodenum through a muscular structure, the sphincter of Oddi.3 The left hepatic duct is longer than the right and has a greater propensity for dilatation as a consequence of distal obstruction. The two ducts join to form a common hepatic duct, close to their emergence from the liver. The common hepatic duct is 1 to 4 cm in length and has a diameter of approximately 4 mm. It lies in front of

31/GALLBLADDER AND THE EXTRAHEPATIC BILIARY SYSTEM

A

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FIG. 31-2. Variations of cystic duct anatomy. A . Low junction between the cystic duct and common hepatic duct. B . Cystic duct adherent to the common hepatic duct. C . High junction between the cystic and the common hepatic duct. D . The cystic duct drains into right hepatic duct. E . Long cystic duct that joins the common hepatic duct behind the duodenum. F . Absence of the cystic duct. G. The cystic duct crosses posterior to the common hepatic duct and joins it anteriorly. H . The cystic duct courses anterior to the common hepatic duct and joins it posteriorly.

the portal vein and to the right of the hepatic artery. The common hepatic duct is joined at an acute angle by the cystic duct to form the common bile duct. The length of the cystic duct is quite variable. It may be short or absent and have a high union with the hepatic duct, or long and run parallel, behind, or spiral to the main hepatic duct before joining it, sometimes as far as at the duodenum. Variations of the cystic duct and its point of union with the common hepatic duct are surgically important (Fig. 31-2). The segment of the cystic duct adjacent to the gallbladder neck bears a variable number of mucosal folds called the spiral valves of Heister. They do not have any valvular function, but may make cannulation of the cystic duct difficult. The common bile duct is about 7 to 11 cm in length and 5 to 10 mm in diameter. The upper third (supraduodenal portion) passes downward in the free edge of the hepatoduodenal ligament, to the right of the hepatic artery and anterior to the portal vein. The middle third (retroduodenal portion) of the common bile duct curves behind the first portion of the duodenum and diverges laterally from the portal vein and the hepatic arteries. The lower third (pancreatic portion) curves behind the head of the pancreas in a groove, or traverses through it and enters the second part of the duodenum. There the pancreatic duct frequently joins it. The common bile duct runs obliquely downward within the wall of the duodenum for 1 to

2 cm before opening on a papilla of mucous membrane (ampulla of Vater), about 10 cm distal to the pylorus. The union of the common bile duct and the main pancreatic duct follows one of three configurations. In about 70% of people these ducts unite outside the duodenal wall and traverse the duodenal wall as a single duct. In about 20%, they join within the duodenal wall and have a short or no common duct, but open through the same opening into the duodenum. In about 10%, they exit via separate openings into the duodenum. The sphincter of Oddi, a thick coat of circular smooth muscle, surrounds the common bile duct at the ampulla of Vater (Fig. 31-3). It controls the flow of bile, and in some cases pancreatic juice, into the duodenum. The extrahepatic bile ducts are lined by a columnar mucosa with numerous mucous glands in the common bile duct. A fibroareolar tissue containing scant smooth muscle cells surrounds the mucosa. A distinct muscle layer is not present in the human common bile duct. The arterial supply to the bile ducts is derived from the gastroduodenal and the right hepatic arteries, with major trunks running along the medial and lateral walls of the common duct (sometimes referred to as 3 o’clock and 9 o’clock). These arteries anastomose freely within the duct walls. The density of nerve fibers and ganglia increase near the sphincter of Oddi, but the nerve supply to the common bile duct and the sphincter of Oddi is the same as for the gallbladder.1,2

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Duodenal wall Common bile duct

Duodenum

A

B

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D

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F

Pancreatic duct

Sphincter of Oddi

FIG. 31-3. The sphincter of Oddi.

Anomalies The classic description of the extrahepatic biliary tree and its arteries applies only in about one third of patients.4 The gallbladder may have abnormal positions, be intrahepatic, be rudimentary, have anomalous forms, or be duplicated. Isolated congenital absence of the gallbladder is very rare, with a reported incidence of 0.03%. Before the diagnosis is made, the presence of an intrahepatic bladder or anomalous position must be ruled out. Duplication of the gallbladder with two separate cavities and two separate cystic ducts has an incidence of about one in every 4000 persons. This occurs in two major varieties: the more common form in which each gallbladder has its own cystic duct that empties independently into the same or different parts of the extrahepatic biliary tree, and as two cystic ducts that merge before they enter the common bile duct. Duplication is only clinically important when some pathologic processes affect one or both organs. A left-sided gallbladder with a cystic duct emptying into the left hepatic duct or the common bile duct and a retrodisplacement of the gallbladder are both extremely rare. A partial or totally intrahepatic gallbladder is associated with an increased incidence of cholelithiasis. Small ducts (of Luschka) may drain directly from the liver into the body of the gallbladder. If present, but not recognized at the time of a cholecystectomy, a bile leak with the accumulation of bile (biloma) may occur in the abdomen. An accessory right hepatic duct occurs in about 5% of cases. Variations of how the common bile duct enters the duodenum are described above. Anomalies of the hepatic artery and the cystic artery are quite common, occurring in as many as 50% of cases.5 In about 5% of cases there are two right hepatic arteries, one from the common hepatic artery and the other from the superior mesenteric artery. In about 20% of patients the right hepatic artery comes off the superior mesenteric artery. The right hepatic artery may course anterior to

FIG. 31-4. Variations in the arterial supply to the gallbladder. A . The cystic artery from the right hepatic artery, about 80 to 90%. B . The cystic artery from the right hepatic artery (accessory or replacing) from the superior mesenteric artery, about 10%. C . Two cystic arteries, one from the right hepatic, the other from the common hepatic artery, rare. D . Two cystic arteries, one from the left hepatic artery, one from the right hepatic artery, rare. E . The cystic artery branching from the right hepatic artery and running anterior to the common hepatic duct, rare. F . Two cystic arteries arising from the right hepatic artery, rare.

the common duct. The right hepatic artery may be vulnerable during surgical procedures, in particular when it runs parallel to the cystic duct or in the mesentery of the gallbladder. The cystic artery arises from the right hepatic artery in about 90% of cases, but may arise from the left hepatic, common hepatic, gastroduodenal, or superior mesenteric arteries (Fig. 31-4).

PHYSIOLOGY Bile Formation and Composition The liver produces bile continuously and excretes it into the bile canaliculi. The normal adult consuming an average diet produces within the liver 500 to 1000 mL of bile a day. The secretion of bile is responsive to neurogenic, humoral, and chemical stimuli. Vagal stimulation increases secretion of bile, whereas splanchnic nerve stimulation results in decreased bile flow. Hydrochloric acid, partly digested proteins, and fatty acids in the duodenum stimulate the release of secretin from the duodenum that in turn increases bile

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production and bile flow. Bile flows from the liver through to the hepatic ducts, into the common hepatic duct, through the common bile duct, and finally into the duodenum. With an intact sphincter of Oddi, bile flow is directed into the gallbladder. Bile is mainly composed of water, electrolytes, bile salts, proteins, lipids, and bile pigments. Sodium, potassium, calcium, and chlorine have the same concentration in bile as in plasma or extracellular fluid. The pH of hepatic bile is usually neutral or slightly alkaline, but varies with diet; an increase in protein shifts the bile to a more acidic pH. The primary bile salts, cholate and chenodeoxycholate, are synthesized in the liver from cholesterol. They are conjugated there with taurine and glycine, and act within the bile as anions (bile acids) that are balanced by sodium. Bile salts are excreted into the bile by the hepatocyte and aid in the digestion and absorption of fats in the intestines.6 In the intestines, about 80% of the conjugated bile acids are absorbed in the terminal ileum. The remainder is dehydroxylated (deconjugated) by gut bacteria, forming secondary bile acids deoxycholate and lithocholate. These are absorbed in the colon, transported to the liver, conjugated, and secreted into the bile. Eventually, about 95% of the bile acid pool is reabsorbed and returned via the portal venous system to the liver, the so-called enterohepatic circulation. Five percent is excreted in the stool, leaving the relatively small amount of bile acids to have maximum effect. Cholesterol and phospholipids synthesized in the liver are the principal lipids found in bile. The synthesis of phospholipids and cholesterol by the liver is in part regulated by bile acids. The color of the bile is due to the presence of the pigment bilirubin diglucuronide, which is the metabolic product from the breakdown of hemoglobin, and is present in bile in concentrations 100 times greater than in plasma. Once in the intestine, bacteria convert it into urobilinogen, a small fraction of which is absorbed and secreted into the bile.

Gallbladder Function The gallbladder, the bile ducts, and the sphincter of Oddi act together to store and regulate the flow of bile. The main function of the gallbladder is to concentrate and store hepatic bile and to deliver bile into the duodenum in response to a meal.

Absorption and Secretion In the fasting state, approximately 80% of the bile secreted by the liver is stored in the gallbladder. This storage is made possible because of the remarkable absorptive capacity of the gallbladder, as the gallbladder mucosa has the greatest absorptive power per unit area of any structure in the body. It rapidly absorbs sodium, chloride, and water against significant concentration gradients, concentrating the bile as much as tenfold and leading to a marked change in bile composition. This rapid absorption is one of the mechanisms that prevent a rise in pressure within the biliary system under normal circumstances. Gradual relaxation as well as emptying of the gallbladder during the fasting period also plays a role in maintaining a relatively low intraluminal pressure in the biliary tree. The epithelial cells of the gallbladder secrete at least two important products into the gallbladder lumen: glycoproteins and hydrogen ions. The mucosal glands in the infundibulum and the neck of the gallbladder secrete mucus glycoproteins that are believed to protect the mucosa from the lytic action of bile and to facilitate the passage of bile through the cystic duct. This mucus makes up the colorless “white bile” seen in hydrops of the gallbladder resulting from cystic duct obstruction. The transport of hydrogen ions by the gallbladder epithelium leads to a decrease in the gallbladder bile pH.

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The acidification promotes calcium solubility, thereby preventing its precipitation as calcium salts.6

Motor Activity Gallbladder filling is facilitated by tonic contraction of the sphincter of Oddi, which creates a pressure gradient between the bile ducts and the gallbladder. During fasting the gallbladder does not simply fill passively. In association with phase II of the interdigestive migrating myenteric motor complex in the gut, the gallbladder repeatedly empties small volumes of bile into the duodenum. This process is mediated at least in part by the hormone motilin. In response to a meal, the gallbladder empties by a coordinated motor response of gallbladder contraction and sphincter of Oddi relaxation. One of the main stimuli to gallbladder emptying is the hormone cholecystokinin (CCK). CCK is released endogenously from the duodenal mucosa in response to a meal.7 When stimulated by eating, the gallbladder empties 50 to 70% of its contents within 30 to 40 minutes. Over the following 60 to 90 minutes the gallbladder gradually refills. This is correlated with a reduced CCK level. Other hormonal and neural pathways also are involved in the coordinated action of the gallbladder and the sphincter of Oddi. Defects in the motor activity of the gallbladder are thought to play a role in cholesterol nucleation and gallstone formation.8

Neurohormonal Regulation The vagus nerve stimulates contraction of the gallbladder, and splanchnic sympathetic stimulation is inhibitory to its motor activity. Parasympathomimetic drugs contract the gallbladder, whereas atropine leads to relaxation. Neurally mediated reflexes link the sphincter of Oddi with the gallbladder, stomach, and duodenum to coordinate the flow of bile into the duodenum. Antral distention of the stomach causes both gallbladder contraction and relaxation of the sphincter of Oddi. Hormonal receptors are located on the smooth muscles, vessels, nerves, and epithelium of the gallbladder. CCK is a peptide that comes from epithelial cells of the upper gastrointestinal tract and is found in the highest concentrations in the duodenum. CCK is released into the bloodstream by acid, fat, and amino acids in the duodenum.9 CCK has a plasma half-life of 2 to 3 minutes and is metabolized by both the liver and the kidneys. CCK acts directly on smooth muscle receptors of the gallbladder and stimulates gallbladder contraction. It also relaxes the terminal bile duct, the sphincter of Oddi, and the duodenum. CCK stimulation of the gallbladder and the biliary tree also is mediated by cholinergic vagal neurons. In patients who have had a vagotomy, the response to CCK stimulation is diminished and the size and the volume of the gallbladder are increased. VIP inhibits contraction and causes gallbladder relaxation. Somatostatin and its analogues are potent inhibitors of gallbladder contraction. Patients treated with somatostatin analogues and those with somatostatinoma have a high incidence of gallstones, presumably due to the inhibition of gallbladder contraction and emptying. Other hormones such as substance P and enkephalin affect gallbladder motility, but the physiologic role is unclear.7

Sphincter of Oddi The sphincter of Oddi regulates flow of bile (and pancreatic juice) into the duodenum, prevents the regurgitation of duodenal contents into the biliary tree, and diverts bile into the gallbladder. It is a complex structure that is functionally independent from the duodenal

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was the mainstay of investigation for gallstones. In the 1950s biliary scintigraphy was developed, and later transhepatic and endoscopic retrograde cholangiography, allowing imaging of the biliary tract. Later ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), vastly improved the ability to image the biliary tract.11

Blood Tests

A

When patients with suspected diseases of the gallbladder or the extrahepatic biliary tree are evaluated, a complete blood count (CBC) and liver function tests are routinely requested. An elevated white blood cell (WBC) count may indicate or raise suspicion of cholecystitis. If associated with an elevation of bilirubin, alkaline phosphatase, and aminotransferase, cholangitis should be suspected. Cholestasis, an obstruction to bile flow, is characterized by an elevation of bilirubin (i.e., the conjugated form), and a rise in alkaline phosphatase. Serum aminotransferases may be normal or mildly elevated. In patients with biliary colic, blood tests will typically be normal.

Ultrasonography

B FIG. 31-5. The effect of CCK on the gallbladder and the sphincter of Oddi. A . During fasting, with the sphincter of Oddi contracted and the gallbladder filling. B . In response to a meal, the sphincter of Oddi is relaxed and the gallbladder emptying.

musculature and creates a high-pressure zone between the bile duct and the duodenum. The sphincter of Oddi is about 4 to 6 mm in length and has a basal resting pressure of about 13 mm Hg above the duodenal pressure. On manometry, the sphincter shows phasic contractions with a frequency of about four per minute and an amplitude of 12 to 140 mm Hg. The sphincter primarily controls the regulation of bile flow. Relaxation occurs with a rise in CCK, leading to diminished amplitude of phasic contractions and reduced basal pressure, allowing increased flow of bile into the duodenum (Fig. 31-5). During fasting, the sphincter of Oddi activity is coordinated with the periodic partial gallbladder emptying and an increase in bile flow that occurs during phase III of the migrating myoelectric complexes.10

DIAGNOSTIC STUDIES A variety of diagnostic modalities are available for the patient with suspected disease of the gallbladder and the bile ducts. In 1924 the diagnosis of gallstones was improved significantly by the introduction of oral cholecystography by Graham and Cole. For decades it

An ultrasound is the initial investigation of any patient suspected of disease of the biliary tree.12 It is noninvasive, painless, does not submit the patient to radiation, and can be performed on critically ill patients. It is dependent upon the skills and the experience of the operator and it is dynamic (i.e., static images do not give the same information as those obtained during the ultrasound investigation itself). Adjacent organs can frequently be examined at the same time. Obese patients, patients with ascites, and patients with distended bowel may be difficult to examine satisfactorily with an ultrasound. An ultrasound will show stones in the gallbladder with sensitivity and specificity of over 90%. Stones are acoustically dense and reflect the ultrasound waves back to the ultrasonic transducer. Because stones block the passage of sound waves to the region behind them, they also produce an acoustic shadow (Fig. 31-6). Stones also move with changes in position. Polyps may be calcified and reflect shadows, but do not move with change in posture. Some stones form a layer in the gallbladder; others a sediment or sludge. A thickened gallbladder wall and local tenderness indicate cholecystitis. The patient has acute cholecystitis if a layer of edema is seen within the wall of the gallbladder or between the gallbladder and the liver. When a stone obstructs the neck of the gallbladder, the gallbladder may become very large, but thin walled. A contracted, thick-walled gallbladder indicates chronic cholecystitis. The extrahepatic bile ducts are also well visualized by ultrasound, except for the retroduodenal portion. Dilation of the ducts in a patient with jaundice establishes an extrahepatic obstruction as a cause for the jaundice. Frequently the site, and sometimes the cause of obstruction, can be determined by ultrasound. Small stones in the common bile duct frequently get lodged at the distal end of it, behind the duodenum, and are therefore difficult to detect. A dilated common bile duct on ultrasound, small stones in the gallbladder, and the clinical presentation allow one to assume that a stone or stones are causing the obstruction. Periampullary tumors can be difficult to diagnose on ultrasound, but beyond the retroduodenal portion, the level of obstruction and the cause may be visualized quite well. Ultrasound can be helpful in evaluating tumor invasion and flow in the portal vein, an important guideline for resectability of periampullary tumors.13

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FIG. 31-6. An ultrasonogram of the gallbladder. Arrows indicate the acoustic shadows of stones in the gallbladder.

Oral Cholecystography Once the diagnostic procedure of choice for gallstones, oral cholecystography has largely been replaced by ultrasonography. It involves oral administration of a radiopaque compound that is absorbed, excreted by the liver, and passed into the gallbladder. Stones are noted on a film as filling defects in a visualized, opacified gallbladder. Oral cholecystography is of no value in patients with intestinal malabsorption, vomiting, obstructive jaundice, and hepatic failure.

Biliary Radionuclide Scanning (HIDA Scan) Biliary scintigraphy provides a noninvasive evaluation of the liver, gallbladder, bile ducts, and duodenum with both anatomic and functional information. 99m -Technetium-labeled derivatives of dimethyl iminodiacetic acid (HIDA) are injected intravenously, cleared by the Kupffer cells in the liver, and excreted in the bile. Uptake by the liver is detected within 10 minutes, and the gallbladder, the bile ducts, and the duodenum are visualized within 60 minutes in fasting subjects. The primary use of biliary scintigraphy is in the diagnosis of acute cholecystitis, which appears as a nonvisualized gallbladder, with prompt filling of the common bile duct and duodenum. Evidence of cystic duct obstruction on biliary scintigraphy is highly diagnostic for acute cholecystitis. The sensitivity and specificity for the diagnosis is about 95% each. False-positive results are increased in patients with gallbladder stasis, as in critically ill patients and in patients receiving parenteral nutrition. Filling of the gallbladder and common bile duct with delayed or absent filling of the duodenum indicates an obstruction at the ampulla. Biliary leaks as a complication of surgery of the gallbladder or the biliary tree can be confirmed and frequently localized by biliary scintigraphy.14

Computed Tomography Abdominal CT scans are inferior to ultrasonography in diagnosing gallstones. The major application of CT scans is to define the course and status of the extrahepatic biliary tree and adjacent structures. It is the test of choice in evaluating the patient with suspected malignancy of the gallbladder, the extrahepatic biliary system, or nearby organs, in particular the head of the pancreas. Use of CT scan is an integral part of the differential diagnosis of obstructive jaundice (Fig. 31-7). Spiral CT scanning provides additional staging

information, including vascular involvement in patients with periampullary tumors.15

Percutaneous Transhepatic Cholangiography An intrahepatic bile duct is accessed percutaneously with a small needle under fluoroscopic guidance. Once the position in a bile duct has been confirmed, a guidewire is passed and subsequently a catheter passed over the wire (Fig. 31-8). Through the catheter, a cholangiogram can be performed and therapeutic interventions done, such as biliary drain insertions and stent placements. Percutaneous transhepatic cholangiography (PTC) has little role in the management of patients with uncomplicated gallstone disease, but is particularly useful in patients with bile duct strictures and tumors, as it defines the anatomy of the biliary tree proximal to the affected segment. As with any invasive procedure, there are potential risks. For PTC these are mainly bleeding, cholangitis, bile leak, and other catheter-related problems.14

Magnetic Resonance Imaging Available since the mid-1990s, MRI provides anatomic details of the liver, gallbladder, and pancreas similar to those obtained from CT. Using MRI with newer techniques and contrast materials, accurate anatomic images can be obtained of the bile ducts and the pancreatic duct. It has a sensitivity and specificity of 95 and 89%, respectively, at detecting choledocholithiasis.16 If available, MRI with magnetic resonance cholangiopancreatography (MRCP) offers a single noninvasive test for the diagnosis of biliary tract and pancreatic disease17 (Fig. 31-9).

Endoscopic Retrograde Cholangiography and Endoscopic Ultrasound Using a side-viewing endoscope, the common bile duct can be cannulated and a cholangiogram performed using fluoroscopy (Fig. 3110). The procedure requires intravenous sedation for the patient. The advantages of endoscopic retrograde cholangiography (ERC) include direct visualization of the ampullary region and direct access to the distal common bile duct, with the possibility of therapeutic intervention. The test is rarely needed for uncomplicated gallstone disease, but for stones in the common bile duct, in particular when associated with obstructive jaundice, cholangitis, or

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FIG. 31-7. CT scan of the upper abdomen from a patient with cancer of the distal common bile duct. The cancer obstructs the common bile duct as well as the pancreatic duct. 1. The portal vein. 2. A dilated intrahepatic bile duct. 3. Dilated cystic duct and the neck of the gallbladder. 4. Dilated common hepatic duct. 5. The bifurcation of the common hepatic artery into the gastroduodenal artery and the proper hepatic artery. 6. Dilated pancreatic duct. 7. The splenic vein.

gallstone pancreatitis, ERC is the diagnostic and often therapeutic procedure of choice. Once the endoscopic cholangiogram has shown ductal stones, sphincterotomy and stone extraction can be performed, and the common bile duct cleared of stones. In the hands of experts, the success rate of common bile duct cannulation and cholangiography is more than 90%. Complications of diagnostic ERC include pancreatitis and cholangitis, and occur in up to 5% of patients.18 An endoscopic ultrasound requires a special endoscope with an ultrasound transducer at its tip. The results are operator dependent, but offer noninvasive imaging of the bile ducts and adjacent structures. It is of particular value in the evaluation of tumors and their resectability. The ultrasound endoscope has a biopsy channel, allowing needle biopsies of a tumor under ultrasonic guidance. Endoscopic ultrasound also has been used to identify bile duct stones, and although it is less sensitive than ERC, the technique is less invasive.

GALLSTONE DISEASE Prevalence and Incidence Gallstone disease is one of the most common problems affecting the digestive tract. Autopsy reports have shown a prevalence of gallstones from 11 to 36%. The prevalence of gallstones is related to many factors, including age, gender, and ethnic background. Certain conditions predispose to the development of gallstones. Obesity, pregnancy, dietary factors, Crohn’s disease, terminal ileal resection, gastric surgery, hereditary spherocytosis, sickle cell disease, and thalassemia are all associated with an increased risk of developing

gallstones.8 Women are three times more likely to develop gallstones than men, and first-degree relatives of patients with gallstones have a twofold greater prevalence.19

Natural History Most patients will remain asymptomatic from their gallstones throughout life. For unknown reasons some patients progress to a symptomatic stage, with biliary colic caused by a stone obstructing the cystic duct. Symptomatic gallstone disease may progress to complications related to the gallstones.20 These include acute cholecystitis, choledocholithiasis with or without cholangitis, gallstone pancreatitis, cholecystocholedochal fistula, cholecystoduodenal fistula, cholecystoenteric fistula leading to gallstone ileus, and gallbladder carcinoma. Rarely, complication of gallstones is the presenting picture. Gallstones in patients without biliary symptoms are commonly diagnosed incidentally on ultrasonography, CT scans, abdominal radiography, or at laparotomy. Several studies have examined the likelihood of developing biliary colic or developing significant complications of gallstone disease. Approximately 3% of asymptomatic individuals become symptomatic per year (i.e., develop biliary colic). Once symptomatic, patients tend to have recurring bouts of biliary colic. Complicated gallstone disease develops in 3 to 5% of symptomatic patients per year. Over a 20-year period, about two thirds of asymptomatic patients with gallstones remain symptom free. Since few patients develop complications without previous biliary symptoms, prophylactic cholecystectomy in asymptomatic

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B A

C

FIG. 31-8. Schematic diagram of percutaneous transhepatic cholangiogram (PTC) and drainage for an obstructing proximal cholangiocarcinoma. A . The dilated intrahepatic bile duct is entered percutaneously with a fine needle. B . A small guidewire is passed through the needle into the duct. C . A plastic catheter has been passed over the wire, and the wire is subsequently removed. A cholangiogram is performed through the catheter. D . An external drainage catheter in place. E . A long wire is placed via the catheter and advanced past the tumor and into the duodenum. F . An internal stent has been placed through the tumor.

D

E

persons with gallstones is rarely indicated. For elderly patients with diabetes, for individuals who will be isolated from medical care for extended periods of time, and in populations with increased risk of gallbladder cancer, a prophylactic cholecystectomy may be advisable. Porcelain gallbladder, a rare premalignant condition in which the wall of the gallbladder becomes calcified, is an absolute indication for cholecystectomy.

F

Gallstone Formation Gallstones form as a result of solids settling out of solution. The major organic solutes in bile are bilirubin, bile salts, phospholipids, and cholesterol. Gallstones are classified by their cholesterol content as either cholesterol stones or pigment stones. Pigment stones can be further classified as either black or brown. In Western countries,

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FIG. 31-9. Magnetic resonance cholangiopancreatography (MRCP). This view shows the course of the extrahepatic bile ducts (arrow) and the pancreatic duct (arrowheads).

about 80% of gallstones are cholesterol stones and about 15 to 20% are black pigment stones. Brown pigment stones account for only a small percentage. Both types of pigment stones are more common in Asia.

Cholesterol Stones Pure chlolesterol stones are uncommon and account for less than 10% of all stones. They usually occur as single large stones with smooth surfaces. Most other cholesterol stones contain variable amounts of bile pigments and calcium, but are always more than 70% cholesterol by weight. These stones are usually multiple, of variable size, and may be hard and faceted or irregular, mulberryshaped and soft (Fig. 31-11). Colors range from whitish yellow and green to black. Most cholesterol stones are radiolucent; less than 10% are radiopaque. Whether pure or of mixed nature, the common primary event in the formation of cholesterol stones is supersaturation of bile with cholesterol. Therefore high bile cholesterol levels and cholesterol gallstones are considered as one disease. Cholesterol is highly nonpolar and insoluble in water and bile. Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and lecithin (the main phospholipid in bile). Supersaturation almost always is caused by cholesterol hypersecretion rather than by a reduced secretion of phospholipid or bile salts.2 Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. Cholesterol is held in solution by micelles, a conjugated bile salt-phospholipid-cholesterol complex, as well as by the cholesterolphospholipid vesicles. The presence of vesicles and micelles in the

same aqueous compartment allows the movement of lipids between the two. Vesicular maturation occurs when vesicular lipids are incorporated into micelles. Vesicular phospholipids are incorporated into micelles more readily than vesicular cholesterol. Therefore vesicles may become enriched in cholesterol, become unstable, and nucleate cholesterol crystals. In unsaturated bile, cholesterol enrichment of vesicles is inconsequential. In the supersaturated bile, cholesterol-dense zones develop on the surface of the cholesterolenriched vesicles, leading to the appearance of cholesterol crystals. About one third of biliary cholesterol is transported in micelles, but the cholesterol-phospholipid vesicles carry the majority of biliary cholesterol21 (Fig. 31-12).

Pigment Stones Pigment stones contain less than 20% cholesterol and are dark because of the presence of calcium bilirubinate. Otherwise, black and brown pigment stones have little in common and should be considered as separate entities. Black pigment stones are usually small, brittle, black, and sometimes spiculated. They are formed by supersaturation of calcium bilirubinate, carbonate, and phosphate, most often secondary to hemolytic disorders such as hereditary spherocytosis and sickle cell disease, and in those with cirrhosis. Like cholesterol stones, they almost always form in the gallbladder. Unconjugated bilirubin is much less soluble than conjugated bilirubin in bile. Deconjugation of bilirubin occurs normally in bile at a slow rate. Excessive levels of conjugated bilirubin, as in hemolytic states, lead to an increased

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A

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B FIG. 31-10. Endoscopic retrograde cholangiography (ERC). A . A schematic picture showing the sideviewing endoscope in the duodenum and a catheter in the common bile duct. B . An endoscopic cholangiography showing stones in the common bile duct. The catheter has been placed in the ampulla of vater (arrow). Note the duodenal shadow indicated with arrowheads.

rate of production of unconjugated bilirubin. Cirrhosis may lead to increased secretion of unconjugated bilirubin. When altered conditions lead to increased levels of deconjugated bilirubin in bile, precipitation with calcium occurs. In Asian countries such as Japan, black stones account for a much higher percentage of gallstones than in the Western hemisphere. Brown stones are usually less than 1 cm in diameter, brownishyellow, soft, and often mushy. They may form either in the

gallbladder or in the bile ducts, usually secondary to bacterial infection caused by bile stasis. Precipitated calcium bilirubinate and bacterial cell bodies compose the major part of the stone. Bacteria such as Escherichia coli secrete beta-glucuronidase that enzymatically cleaves bilirubin glucuronide to produce the insoluble unconjugated bilirubin. It precipitates with calcium, and along with dead bacterial cell bodies, forms soft brown stones in the biliary tree. Brown stones are typically found in the biliary tree of Asian populations and are associated with stasis secondary to parasite infection. In Western populations, brown stones occur as primary bile duct stones in patients with biliary strictures or other common bile duct stones that cause stasis and bacterial contamination.2,22

Symptomatic Gallstones Chronic Cholecystitis About two thirds of patients with gallstone disease present with chronic cholecystitis characterized by recurrent attacks of pain, often inaccurately labeled biliary colic. The pain develops when a stone obstructs the cystic duct, resulting in a progressive increase of tension in the gallbladder wall. The pathologic changes, which often do not correlate well with symptoms, vary from an apparently normal gallbladder with minor chronic inflammation in the mucosa, to a shrunken, nonfunctioning gallbladder with gross transmural fibrosis and adhesions to nearby structures. The mucosa is initially normal or hypertrophied, but later becomes atrophied, with the epithelium protruding into the muscle coat, leading to the formation of the so-called Aschoff-Rokitansky sinuses. FIG. 31-11. Gallbladder with cholesterol stones. Note the different shapes and sizes.

Clinical Presentation. The chief symptom associated with symptomatic gallstones is pain. The pain is constant and increases in

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2 2 14

15 7 64

2

50 24 13 5 4

1

9

6 4

1

4

A

3

FIG. 31-12. The three major components of bile plotted on triangular coordinates. A given point represents the relative molar ratios of bile salts, lecithin, and cholesterol. The area labelled “micellar liquid” shows the range of concentrations found consistent with a clear micellar solution (single phase), where cholesterol is fully solubilized. The shaded area directly above this region corresponds to a metastable zone, supersaturated with cholesterol. Bile with a composition that falls above the shaded area has exceeded the solubilization capacity of cholesterol and precipitation of cholesterol crystals occurs. [Reproduced with permission from Holzbach RT: Pathogenesis and medical treatment of gallstones, in Slesinger MH, Fordtran JS (eds): Gastrointestinal Diseases. Philadelphia: WB Saunders, 1989, p 1360.]

severity over the first half hour or so and typically lasts 1 to 5 hours. It is located in the epigastrium or right upper quadrant and frequently radiates to the right upper back or between the scapulae (Fig. 31-13). The pain is severe and comes on abruptly, typically during the night or after a fatty meal. It often is associated with nausea and sometimes vomiting. The pain is episodic. The patient suffers discrete attacks of pain, between which they feel well. Physical examination may reveal mild right upper quadrant tenderness during an episode of pain. If the patient is pain free, the physical exam is usually unremarkable. Laboratory values, such as white blood cell count and liver function tests, are usually normal in patients with uncomplicated gallstones. Atypical presentation of gallstone disease is common. Association with meals is present in only about 50% of patients. Some patients report milder attacks of pain, but relate it to meals. The pain may be located primarily in the back or the left upper or lower right quadrant. Bloating and belching may be present and associated with the attacks of pain. In patients with atypical presentation, other conditions with upper abdominal pain should be sought out, even in the presence of gallstones. These include peptic ulcer disease, gastroesophageal reflux disease, abdominal wall hernias, irritable bowel disease, diverticular disease, liver diseases, renal calculi, pleuritic pain, and myocardial pain. Many patients with other conditions have gallstones. When the pain lasts more than 24 hours, an impacted stone in the cystic duct or acute cholecystitis (see below) should be suspected. An impacted stone will result in what is called hydrops of the gallbladder. The bile gets absorbed, but the gallbladder epithelium continues to secrete mucus and the gallbladder becomes distended with

9 1

6

2 19

3 15 2

5

2 11

11 2

35 33 3

3 2

B FIG. 31-13. A . Sites of the most severe pain during an episode of biliary pain in 107 patients with gallstones (values add up to more than 100% because of multiple responses). The subxiphoid and right subcostal areas were the most common sites; note that the left subcostal area was not an unusual site of pain. B . Sites of pain radiation (%) during an episode of biliary pain in the same group of patients. (Reproduced with permission from Gunn A, Keddie N: Some clinical observations on patients with gallstones. Lancet 2:230, 2004.)

mucinous material. The gallbladder may be palpable, but usually is not tender. Hydrops of the gallbladder may result in edema of the gallbladder wall, inflammation, infection, and perforation. Although hydrops may persist with few consequences, early cholecystectomy is generally indicated to avoid complications.

Diagnosis. The diagnosis of symptomatic gallstones or chronic calculous cholecystitis depends on the presence of typical symptoms and the demonstration of stones on diagnostic imaging. An abdominal ultrasound is the standard diagnostic test for gallstones (see above).23 Gallstones are occasionally identified on abdominal radiographs or CT scans. In these cases, if the patient has typical symptoms, an ultrasound of the gallbladder and the biliary tree should be added prior to surgical intervention. Stones diagnosed incidentally in patients without symptoms should be left in place as discussed previously. Occasionally, patients with typical attacks of biliary pain have no evidence of stones on ultrasonography.

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Sometimes only sludge in the gallbladder is demonstrated on ultrasonography. If the patient has recurrent attacks of typical biliary pain and sludge is detected on two or more occasions, cholecystectomy is warranted. In addition to sludge and stones, cholesterolosis and adenomyomatosis of the gallbladder may cause typical biliary symptoms and may be detected on ultrasonography. Cholesterolosis is caused by the accumulation of cholesterol in macrophages in the gallbladder mucosa, either locally or as polyps. It produces the classic macroscopic appearance of a “strawberry gallbladder.” Adenomyomatosis or cholecystitis glandularis proliferans is characterized on microscopy by hypertrophic smooth muscle bundles and by the ingrowths of mucosal glands into the muscle layer (epithelial sinus formation). Granulomatous polyps develop in the lumen at the fundus, and the gallbladder wall is thickened and septae or strictures may be seen in the gallbladder. In symptomatic patients, cholecystectomy is the treatment of choice for patients with these conditions.24

Management. Patients with symptomatic gallstones should be advised to have elective laparoscopic cholecystectomy. While waiting for surgery, or if surgery has to be postponed, the patient should be advised to avoid dietary fats and large meals. Diabetic patients with symptomatic gallstones should have a cholecystectomy promptly, as they are more prone to develop acute cholecystitis that is often severe. Pregnant women with symptomatic gallstones who cannot be managed expectantly with diet modifications can safely undergo laparoscopic cholecystectomy during the second trimester. Laparoscopic cholecystectomy is safe and effective in children as well as in the elderly. Cholecystectomy, open or laparoscopic, for patients with symptomatic gallstones offers excellent long-term results. About 90% of patients with typical biliary symptoms and stones are rendered symptom free after cholecystectomy. For patients with atypical symptoms or dyspepsia (flatulence, belching, bloating, and dietary fat intolerance) the results are not as favorable. Acute Cholecystitis Pathogenesis. Acute cholecystitis is secondary to gallstones in 90 to 95% of cases. Acute acalculous cholecystitis is a condition that typically occurs in patients with other acute systemic diseases (see acalculous cholecystitis section, below). In less than 1% of acute cholecystitis, the cause is a tumor obstructing the cystic duct. Obstruction of the cystic duct by a gallstone is the initiating event that leads to gallbladder distention, inflammation, and edema of the gallbladder wall. Why inflammation develops only occasionally with cystic duct obstruction is unknown. It is probably related to the duration of obstruction of the cystic duct. Initially, acute cholecystitis is an inflammatory process, possibly mediated by lysolecithin, a product of lecithin, as well as bile salts and platelet-activating factor. Secondary bacterial contamination is documented in over one half of patients undergoing early cholecystectomy for acute uncomplicated cholecystitis. In acute cholecystitis the gallbladder wall becomes grossly thickened and reddish with subserosal hemorrhages. Pericholecystic fluid often is present. The mucosa may show hyperemia and patchy necrosis. In severe cases, about 5 to 10%, the inflammatory process progresses and leads to ischemia and necrosis of the gallbladder wall. More frequently, the gallstone is dislodged and the inflammation resolves.25 When the gallbladder remains obstructed and secondary bacterial infection supervenes, an acute gangrenous cholecystitis develops and an abscess or empyema forms within the gallbladder. Rarely, perforation of ischemic areas occurs. The perforation is usually contained in the subhepatic space by the omentum and adjacent organs.

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However, free perforation with peritonitis, intrahepatic perforation with intrahepatic abscesses, and perforation into adjacent organs (duodenum or colon) with cholecystoenteric fistula occur. When gas-forming organisms are part of the secondary bacterial infection, gas may be seen in the gallbladder lumen and in the wall of the gallbladder on abdominal radiographs and CT scans, an entity called an emphysematous gallbladder.

Clinical Manifestations. About 80% of patients with acute cholecystitis give a history compatible with chronic cholecystitis. Acute cholecystitis begins as an attack of biliary colic, but in contrast to biliary colic, the pain does not subside; it is unremitting and may persist for several days. The pain is typically in the right upper quadrant or epigastrium, and may radiate to the right upper part of the back or the interscapular area. It is usually more severe than the pain associated with uncomplicated biliary colic. The patient is often febrile, complains of anorexia, nausea, and vomiting, and is reluctant to move, as the inflammatory process affects the parietal peritoneum. On physical exam, focal tenderness and guarding are usually present in the right upper quadrant. A mass, the gallbladder and adherent omentum, is occasionally palpable; however, guarding may prevent this. A Murphy’s sign, an inspiratory arrest with deep palpation in the right subcostal area, is characteristic of acute cholecystitis. A mild to moderate leukocytosis (12,000 to 15,000 cells/mm3 ) is usually present. However, some patients may have a normal WBC. A high WBC (above 20,000) is suggestive of a complicated form of cholecystitis such as gangrenous cholecystitis, perforation, or associated cholangitis. Serum liver chemistries are usually normal, but a mild elevation of serum bilirubin, less than 4 mg/mL, may be present along with mild elevation of alkaline phosphatase, transaminases, and amylase.23 Severe jaundice is suggestive of common bile duct stones or obstruction of the bile ducts by severe pericholecystic inflammation secondary to impaction of a stone in the infundibulum of the gallbladder that mechanically obstructs the bile duct (Mirizzi’s syndrome). In elderly patients and in those with diabetes mellitus, acute cholecystitis may have a subtle presentation resulting in a delay in diagnosis. The incidence of complications is higher in these patients, who also have approximately tenfold the mortality rate compared to that of younger and healthier patients. The differential diagnosis for acute cholecystitis includes a peptic ulcer with or without perforation, pancreatitis, appendicitis, hepatitis, perihepatitis (Fitz-Hugh and Curtis syndrome), myocardial ischemia, pneumonia, pleuritis, and herpes zoster involving the intercostal nerve. Diagnosis. Ultrasonography is the most useful radiologic test for diagnosing acute cholecystitis. It has a sensitivity and specificity of 95%. In addition to being a sensitive test for documenting the presence or absence of stones, it will show the thickening of the gallbladder wall and the pericholecystic fluid (Fig. 31-14). Focal tenderness over the gallbladder when compressed by the sonographic probe (sonographic Murphy’s sign) also is suggestive of acute cholecystitis. Biliary radionuclide scanning (HIDA scan) may be of help in the atypical case. Lack of filling of the gallbladder after 4 hours indicates an obstructed cystic duct, and in the clinical setting of acute cholecystitis is highly sensitive and specific for acute cholecystitis. A normal HIDA scan excludes acute cholecystitis. CT scan is frequently performed on patients with acute abdominal pain. It demonstrates thickening of the gallbladder wall, pericholecystic fluid, and the presence of gallstones as well as air in the gallbladder wall, but is less sensitive than ultrasonography.

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FIG. 31-14. Ultrasonography from a patient with acute cholecystitis. The arrowheads indicate the thickened gallbladder wall. There are several stones in the gallbladder (arrows) throwing acoustic shadows.

Treatment. Patients who present with acute cholecystitis will need intravenous fluids, antibiotics, and analgesia. The antibiotics should cover gram-negative aerobes as well as anaerobes. A thirdgeneration cephalosporin with good anaerobic coverage or a secondgeneration cephalosporin combined with metronidazole are typical regimens. For patients with allergies to cephalosporins an aminoglycoside with metronidazole is appropriate. Although the inflammation in acute cholecystitis may be sterile in some patients, more than one half will have positive cultures from the gallbladder bile. It is difficult to know who is secondarily infected; therefore antibiotics have become a part of the management in most medical centers. Cholecystectomy is the definitive treatment for acute cholecystitis.26 The timing of cholecystectomy has been a matter of debate in the past. Early cholecystectomy performed within 2 to 3 days of the illness is preferred over interval or delayed cholecystectomy that is performed 6 to 10 weeks after initial medical treatment and recuperation. Several studies have shown that unless the patient is unfit for surgery, early cholecystectomy should be recommended as it offers the patient a definitive solution in one hospital admission, quicker recovery times, and an earlier return to work.27 Laparoscopic cholecystectomy is the procedure of choice for acute cholecystitis. The conversion rate to an open cholecystectomy is higher (10 to 15%) in the setting of acute cholecystitis than with chronic cholecystitis. The procedure is more tedious and takes longer than in the elective setting. However, when compared to the delayed operation, early operation carries a similar number of complications. When patients present late, after 3 to 4 days of illness, or are for some reason unfit for surgery, they are treated with antibiotics with laparoscopic cholecystectomy scheduled for approximately 2 months later. Approximately 20% of patients will fail to respond to initial medical therapy and require an intervention. Laparoscopic cholecystectomy could be attempted, but the conversion rate is high and some prefer to go directly for an open cholecystectomy. For those unfit for surgery, a percutaneous cholecystostomy or an open cholecystostomy under local analgesia can be performed. Failure to improve after cholecystostomy usually is due to gangrene of the gallbladder or perforation. For these patients, surgery is unavoidable. For those who respond after cholecystostomy, the tube can be

removed once cholangiography through it shows a patent ductus cysticus. Laparoscopic cholecystectomy may then be scheduled in the near future.28 For the occasional patient who will not tolerate surgery, the stones can be extracted via the cholecystostomy tube before its removal.

Choledocholithiasis Common bile duct stones may be small or large, single or multiple, and are found in 6 to 12% of patients with stones in the gallbladder. The incidence increases with age. About 20 to 25% of patients above the age of 60 with symptomatic gallstones have stones in the common bile duct as well as in the gallbladder.29 The vast majority of ductal stones in Western countries are formed within the gallbladder and migrate down the cystic duct to the common bile duct. These are classified as secondary common bile duct stones, in contrast to the primary stones that form in the bile ducts. The secondary stones are usually cholesterol stones, whereas the primary stones are usually of the brown pigment type. The primary stones are associated with biliary stasis and infection and are more commonly seen in Asian populations. The causes of biliary stasis that lead to the development of primary stones include biliary stricture, papillary stenosis, tumors, or other (secondary) stones.

Clinical Manifestations. Choledochal stones may be silent and often are discovered incidentally. They may cause obstruction, complete or incomplete, or they may manifest with cholangitis or gallstone pancreatitis. The pain caused by a stone in the bile duct is very similar to that of biliary colic caused by impaction of a stone in the cystic duct. Nausea and vomiting are common. Physical exam may be normal, but mild epigastric or right upper quadrant tenderness as well as mild icterus are common. The symptoms may also be intermittent, such as pain and transient jaundice caused by a stone that temporarily impacts the ampulla but subsequently moves away, acting as a ball valve. A small stone may pass through the ampulla spontaneously with resolution of symptoms. Finally the stones may become completely impacted, causing severe progressive jaundice. Elevation of serum bilirubin, alkaline phosphatase, and transaminases are commonly seen in patients with bile duct stones. However, in about one third of patients with common bile duct stones, the liver chemistries are normal.

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A

C

B FIG. 31-15. An endoscopic sphincterotomy. A . The sphincterotome in place. B . Completed sphincterotomy. C . Endoscopic picture of completed sphincterotomy.

Commonly the first test, ultrasonography, is useful for documenting stones in the gallbladder (if they are still present), as well as determining the size of the common bile duct. As stones in the bile ducts tend to move down to the distal part of the common duct, bowel gas can preclude their demonstration on ultrasonography. A dilated common bile duct (>8 mm in diameter) on ultrasonography in a patient with gallstones, jaundice, and biliary pain is highly suggestive of common bile duct stones. Magnetic resonance cholangiography (MRC) provides excellent anatomic detail and has a sensitivity and specificity of 95 and 89%, respectively, at detecting choledocholithiasis.17 Endoscopic cholangiography is the gold standard for diagnosing common bile duct stones. It has the distinct advantage of providing a therapeutic option at the time of diagnosis. In experienced hands, cannulation of the ampulla of Vater and diagnostic cholangiography are achieved in over 90% of cases, with associated morbidity of less than 5% (mainly cholangitis and pancreatitis). An endoscopic ultrasound is less sensitive, but can be done in nearly every patient without associated complications. PTC is rarely needed in patients with secondary common bile duct stones, but is frequently performed for both diagnostic and therapeutic reasons in patients with primary bile duct stones.

Treatment. For patients with symptomatic gallstones and suspected common bile duct stones, either preoperative endoscopic cholangiography or an intraoperative cholangiogram will document

the bile duct stones.30 If an endoscopic cholangiogram reveals stones, sphincterotomy and ductal clearance of the stones is appropriate, followed by a laparoscopic cholecystectomy. An intraoperative cholangiogram at the time of cholecystectomy will also document the presence or absence of bile duct stones31 (Fig. 31-15). Laparoscopic common bile duct exploration via the cystic duct or with formal choledochotomy allows the stones to be retrieved in the same setting (see next section). If the expertise and/or the instruments for laparoscopic common bile duct exploration are not available, a drain should be left adjacent to the cystic duct and the patient scheduled for endoscopic sphincterotomy the following day. An open common bile duct exploration is an option if the endoscopic method has already been tried or is for some reason not feasible. If a choledochotomy is performed, a T tube is left in place. Stones impacted in the ampulla may be difficult for both endoscopic ductal clearance as well as common bile duct exploration (open or laparoscopic). In these cases the common bile duct is usually quite dilated (about 2 cm in diameter). A choledochoduodenostomy or a Roux-en-Y choledochojejunostomy may be the best option for these circumstances.32 Retained or recurrent stones following cholecystectomy are best treated endoscopically (Fig. 31-16). If the stones were deliberately left in place at the time of surgery or diagnosed shortly after the cholecystectomy, they are classified as retained; those diagnosed months or years later are termed recurrent. If a common bile duct

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A

B

exploration was performed and a T tube left in place, a T-tube cholangiogram is obtained prior to its removal. Retained stones can be retrieved either endoscopically or via the T-tube tract once it has matured (2 to 4 weeks). The T tube is then removed and a catheter passed through the tract into the common bile duct. Under fluoroscopic guidance the stones are retrieved with baskets or balloons.

FIG. 31-16. Retained common bile duct stones. The patient presented 3 weeks after laparoscopic cholecystectomy. A . An ultrasound shows a normal or mildly dilated common bile duct with a stone. Note the location of the right hepatic artery anterior to the common hepatic duct (an anatomic variation). B . An ERC from the same patient shows multiple stones in the common bile duct. Only the top one showed on ultrasound, as the other stones lie in the distal common bile duct behind the duodenum.

Recurrent stones may be multiple and large. A generous endoscopic sphincterotomy will allow stone retrieval as well as spontaneous passage of retained and recurrent stones. Patients over the age of 70 presenting with bile duct stones should have their ductal stones cleared endoscopically. They do not need to be submitted for a cholecystectomy, as only about 15% will become symptomatic from their

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gallbladder stones, and such patients can be treated as the need arises by a cholecystectomy.

Cholangitis Cholangitis is one of the two main complications of choledochal stones, the other being gallstone pancreatitis. Acute cholangitis is an ascending bacterial infection in association with partial or complete obstruction of the bile ducts. Hepatic bile is sterile, and bile in the bile ducts is kept sterile by continuous bile flow and by the presence of antibacterial substances in bile such as immunoglobulin. Mechanical hindrance to bile flow facilitates bacterial contamination. Positive bile cultures are common in the presence of bile duct stones as well as with other causes of obstruction. Biliary bacterial contamination alone does not lead to clinical cholangitis; the combination of both significant bacterial contamination and biliary obstruction is required for its development. Gallstones are the most common cause of obstruction in cholangitis; other causes are benign and malignant strictures, parasites, instrumentation of the ducts and indwelling stents, and partially obstructed biliary-enteric anastomosis. The most common organisms cultured from bile in patients with cholangitis include Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, and Bacteroides fragilis.33

Clinical Presentation. Cholangitis may present as anything from a mild, intermittent, and self-limited disease to a fulminant, potentially life-threatening septicemia. The patient with gallstoneinduced cholangitis is typically older and female. The most common presentation is fever, epigastric or right upper quadrant pain, and jaundice. These classic symptoms, well known as Charcot’s triad, are present in about two thirds of patients. The illness may progress rapidly with septicemia and disorientation, known as Reynolds pentad (e.g., fever, jaundice, right upper quadrant pain, septic shock, and mental status changes). However, the presentation may be atypical, with little if any fever, jaundice, or pain. This occurs most commonly in the elderly, who may have unremarkable symptoms until they collapse with septicemia. Patients with indwelling stents rarely become jaundiced. On abdominal examination, the findings are indistinguishable from those of acute cholecystitis.34 Diagnosis and Management. Leukocytosis, hyperbilirubinemia, and elevation of alkaline phosphatase and transaminases are common, and when present, support the clinical diagnosis of cholangitis. Ultrasonography is helpful if the patient has not been diagnosed previously with gallstones, as it will document the presence of gallbladder stones, demonstrate dilated ducts, and possibly pinpoint the site of obstruction; however, rarely will it elucidate the cause. The definitive diagnostic test is ERC. In cases in which ERC is not available, PTC is indicated. Both ERC and PTC will show the level and the reason for the obstruction, allow culture of the bile, possibly allow the removal of stones if present, and drainage of the bile ducts with drainage catheters or stents. CT scanning and MRI will show pancreatic and periampullary masses, if present, in addition to the ductal dilatation. The initial treatment of patients with cholangitis includes intravenous antibiotics and fluid resuscitation. These patients may require intensive care unit monitoring and vasopressor support. Most patients will respond to these measures. However, the obstructed bile duct must be drained as soon as the patient has been stabilized. About 15% of patients will not respond to antibiotics and fluid resuscitation, and an emergency biliary decompression may be required. Biliary decompression may be accomplished endoscopically, via the percutaneous transhepatic route, or surgically. The selection of

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procedure should be based on the level and the nature of the biliary obstruction. Patients with choledocholithiasis or periampullary malignancies are best approached endoscopically, with sphincterotomy and stone removal, or by placement of an endoscopic biliary stent.35 In patients in whom the obstruction is more proximal or perihilar, or when a stricture in a biliary-enteric anastomosis is the cause or the endoscopic route has failed, percutaneous transhepatic drainage is used. Where neither ERC nor PTC is possible, an emergent operation and decompression of the common bile duct with a T tube may be necessary and life-saving. Definitive operative therapy should be deferred until the cholangitis has been treated and the proper diagnosis established. Patients with indwelling stents and cholangitis usually require repeated imaging and exchange of the stent over a guidewire. Acute cholangitis is associated with an overall mortality rate of approximately 5%. When associated with renal failure, cardiac impairment, hepatic abscesses, and malignancies, the morbidity and mortality rates are much higher.

Biliary Pancreatitis Gallstones in the common bile duct are associated with acute pancreatitis. Obstruction of the pancreatic duct by an impacted stone or temporary obstruction by a stone passing through the ampulla may lead to pancreatitis. The exact mechanism by which the obstruction of the pancreatic duct leads to pancreatitis is still not clear. An ultrasonogram of the biliary tree in patients with pancreatitis is essential. If gallstones are present and the pancreatitis is severe, an ERC with sphincterotomy and stone extraction may abort the episode of pancreatitis. Once the pancreatitis has subsided, the gallbladder should be removed during the same admission. When gallstones are present and the pancreatitis is mild and self-limited, the stone has probably passed. For these patients a cholecystectomy and an intraoperative cholangiogram or a preoperative ERC is indicated.

Cholangiohepatitis Cholangiohepatitis, also known as recurrent pyogenic cholangitis, is endemic to the Orient. It also has been encountered in the Chinese population in the United States as well as in Europe and Australia. It affects both sexes equally and occurs most frequently in the third and fourth decades of life. Cholangiohepatitis is caused by bacterial contamination (commonly E. coli, Klebsiella species, Bacteroides species, or Enterococcus faecalis) of the biliary tree, and often is associated with biliary parasites such as Clonorchis sinensis, Opisthorchis viverrini, and Ascaris lumbricoides. Bacterial enzymes cause deconjugation of bilirubin, which precipitates as bile sludge. The sludge and dead bacterial cell bodies form brown pigment stones. The nucleus of the stone may contain an adult Clonorchis worm, an ovum, or an ascarid. These stones are formed throughout the biliary tree and cause partial obstruction that contributes to the repeated bouts of cholangitis. Biliary strictures form as a result of recurrent cholangitis and lead to further stone formation, infection, hepatic abscesses, and liver failure (secondary biliary cirrhosis).36 The patient usually presents with pain in the right upper quadrant and epigastrium, fever, and jaundice. Recurrence of symptoms is one of the most characteristic features of the disease. The episodes may vary in severity, but without intervention will gradually lead to malnutrition and hepatic insufficiency. An ultrasound will detect stones in the biliary tree, pneumobilia from infection due to gas-forming organisms, liver abscesses, and occasionally strictures. The gallbladder may be thickened, but is inflamed in about 20%

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of patients, and rarely contains stones. MRCP and PTC are the mainstays of biliary imaging for cholangiohepatitis. They can detect obstructions, define strictures and stones, and allow emergent decompression of the biliary tree in the septic patient. Hepatic abscesses may be drained percutaneously. The long-term goal of therapy is to extract stones and debris and relieve strictures. It may take several procedures and require a Roux-en-Y hepaticojejunostomy to establish biliary-enteric continuity. Occasionally, involved areas of the liver may offer the best form of treatment. Recurrences are common and the prognosis is poor once hepatic insufficiency has developed.37

OPERATIVE INTERVENTIONS FOR GALLSTONE DISEASE Cholecystostomy A cholecystostomy decompresses and drains the distended, inflamed, hydropic, or purulent gallbladder. It is applicable if the patient is not fit to tolerate an abdominal operation.38 Ultrasound guided percutaneous drainage with a pigtail catheter is the procedure of choice. The catheter is inserted over a guidewire that has been passed through the abdominal wall, the liver, and into the gallbladder (Fig. 31-17). By passing the catheter through the liver, the risk of bile leak around the catheter is minimized.39 The catheter can be removed when the inflammation has resolved and the patient’s condition improved. The gallbladder can be removed later if indicated, usually by laparoscopy. Surgical cholecystostomy with a large catheter placed under local anesthesia is rarely required today.

Cholecystectomy Cholecystectomy is the most common major abdominal procedure performed in Western countries. Carl Langenbuch performed the first successful cholecystectomy in 1882, and for over 100 years it was the standard treatment for symptomatic gallbladder stones. Open cholecystectomy was a safe and effective treatment for both acute and chronic cholecystitis. In 1987, laparoscopic cholecystectomy was introduced by Philippe Mouret in France and quickly revolutionized the treatment of gallstones. It not only supplanted open cholecystectomy, but also more or less ended attempts for noninvasive management of gallstones such as extracorporeal shock wave (ESWL) and bile salt therapy. Laparoscopic cholecystectomy

FIG. 31-17. Percutaneous cholecystostomy. A pigtail catheter has been placed through the abdominal wall, the right lobe of the liver, and into the gallbladder.

offers a cure for gallstones with a minimally-invasive procedure, minor pain and scarring, and early return to full activity. Today laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Symptomatic gallstones are the main indication for cholecystectomy. Absolute contraindications for the procedure are uncontrolled coagulopathy and end-stage liver disease. Rarely, patients with severe obstructive pulmonary disease or congestive heart failure (e.g., cardiac ejection fraction 55 y Hematocrit fall >10 points WBC >16,000/mm3 BUN elevation >5 mg/dL Blood glucose >200 mg/dL Serum calcium 350 IU/L Arterial Po2 250 U/dL Base deficit >4 mEq/L Estimated fluid sequestration >6 L Criteria for acute gallstone pancreatitis At admission During the initial 48 h Age >70 y Hematocrit fall >10 points BUN elevation >2 mg/dL WBC >18,000/mm3 Blood glucose >220 mg/dL Serum calcium 400 IU/L Base deficit >5 mEq/L Serum AST >250 U/dL Estimated fluid sequestration >4 L AST = aspartate transaminase; BUN = blood urea nitrogen; LDH = lactate dehydrogenase; Po2 = partial pressure of oxygen; WBC = white blood cell count. source: Reproduced with permission from Ranson JHC: Etiological and prognostic factors in human acute pancreatitis: A review. Am J Gastroenterol 77:633, 1982.

mortality is generally zero; with three to five positive signs, mortality is increased to 10 to 20%. The mortality rate increases to more than 50% when there are more than seven positive Ranson signs. Although prognostic signs are useful in determining the severity of pancreatitis, there are several limitations to the value of these signs. One has to measure all 11 signs to achieve the best predictability of prognosis, and two full days are needed to complete the profile. A delay of 48 hours after admission merely for assessment may squander a valuable opportunity to prevent a complication during this time. It is important to realize that Ranson’s prognostic signs are best used within the initial 48 hours of hospitalization and have not been validated for later time intervals. Although several investigators (Imrie, Banks, Agarwal-Pitchumoni, and others) have proposed modifications to simplify these prognostic criteria throughout the years since their inception, Ranson’s original 11 signs are still the most commonly used. Another set of criteria often used to assess the severity of pancreatitis is the acute physiology and chronic health evaluation (APACHE-II) score. This grading system assesses severity on the basis of quantitative measures of abnormalities of multiple variables, including vital signs and specific laboratory parameters, coupled with the age and chronic health status of the patient. The main advantage of the APACHE-II scoring system is the immediate assessment of the severity of pancreatitis. A score of eight or more at admission is usually considered indicative of severe disease.40

Biochemical Markers The ideal biochemical marker for prognosis of acute pancreatitis should not only have high specificity and sensitivity, but also should be able to discriminate between mild (edematous) and severe (necrotic) disease on admission. While serum enzymes such as

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amylase and lipase are helpful in the diagnosis of pancreatitis, these have no prognostic value. Several recent research studies have suggested additional markers that may have prognostic value, including acute phase proteins such as C-reactive protein (CRP), α2 macroglobulin, PMN-elastase, α1 -antitrypsin, and phospholipase A2 . While CRP measurement is commonly available many of the others are not. Therefore, at this time CRP seems to be the marker of choice in clinical settings. The measurement of IL-6 has recently been shown to distinguish patients with mild or severe forms of the disease. However, these tests have to undergo large-scale evaluations before they can be recommended for routine use. Another prognostic marker under evaluation is urinary–trypsinogen activation peptide (TAP). TAP is a five- to seven-amino acid peptide that is released from the N-terminus of trypsinogen during its activation. In recent studies, Neoptolemos and colleagues have shown a good correlation between the severity of pancreatitis and concentrations of TAP in urine.41 However, further testing and methodologic developments are needed before TAP can be used as a routine prognostic marker.

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boring severe pancreatitis, regardless of their Ranson’s or APACHE scores.42

Treatment The severity of acute pancreatitis covers a broad spectrum of illness, ranging from the mild and self-limiting to the life-threatening necrotizing variety. Regardless of severity, hospitalization of the patient with suspected acute pancreatitis for observation and diagnostic study is usually mandatory. Upon confirmation of the diagnosis, patients with moderate to severe disease should be transferred to the intensive care unit for observation and maximal support. The most important initial treatment is conservative intensive care with the goals of oral food and fluid restriction, replacement of fluids and electrolytes parenterally as assessed by central venous pressure and urinary excretion, and control of pain. In severe acute pancreatitis, or when signs of infection are present, most experts recommend broadspectrum antibiotics (e.g., imipenem) and careful surveillance for complications of the disease (Table 32-5).

Mild Pancreatitis Computed Tomography Scan Computed tomography (CT) scanning with bolus intravenous contrast has become the gold standard for detecting and assessing the severity of pancreatitis. While clinically mild pancreatitis is usually associated with interstitial edema, severe pancreatitis is associated with necrosis. In interstitial pancreatitis, the microcirculation of the pancreas remains intact, and the gland shows uniform enhancement on intravenous, contrast-enhanced CT scan (see Fig. 32-13). In necrotizing pancreatitis, however, the microcirculation is disrupted; therefore the enhancement of the gland on contrast-enhanced CT scan is considerably decreased (Fig. 32-14). The presence of air bubbles on a CT scan is an indication of infected necrosis or pancreatic abscess. Currently, intravenous (bolus), contrast-enhanced CT scanning is routinely performed on patients who are suspected of har-

FIG. 32-14. Necrotizing (infected) acute pancreatitis. The CT image reveals areas of nonperfusion and the presence of gas in the region of severe necrosis, which indicates infection.

Pancreatitis is classified as mild when the patient has no systemic complications, low APACHE-II scores and Ranson’s signs, sustained clinical improvement, and when a CT scan rules out necrotizing pancreatitis. The treatment then is mostly supportive and has the important aim of resting the pancreas through restriction of oral food and fluids. Nasogastric suction and H2 -blockers have routinely been used in this connection, based on the reasoning that even the smallest amount of gastric acid reaching the duodenum could stimulate pancreatic secretion. However, these measures are of little value. The following secretion-inhibiting drugs have also been tried without notable success: atropine, calcitonin, somatostatin, glucagon, and fluorouracil.43 Pancreatitis is also an autodigestive process, and various protease-inhibiting drugs including aprotinin, gabexate mesylate, camostate, and phospholipase A2 inhibitors, as well as fresh frozen

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Table 32-5 Complications of Acute Pancreatitis I. Local A. Pancreatic phlegmon B. Pancreatic abscess C. Pancreatic pseudocyst D. Pancreatic ascites E. Involvement of adjacent organs, with hemorrhage, thrombosis, bowel infarction, obstructive jaundice, fistula formation, or mechanical obstruction. II. Systemic A. Pulmonary Pneumonia, atelectasis Acute respiratory distress syndrome Pleural effusion B. Cardiovascular Hypotension Hypovolemia Sudden death Nonspecific ST-T wave changes Pericardial effusion C. Hematologic Hemoconcentration Disseminated intravascular coagulopathy D. Gastrointestinal hemorrhage Peptic ulcer Erosive gastritis Portal vein or splenic vein thrombosis with varices E. Renal Oliguria Azotemia Renal artery/vein thrombosis F. Metabolic Hyperglycemia Hypocalcemia Hypertriglyceridemia Encephalopathy Sudden blindness (Purtscher’s retinopathy) G. Central nervous system Psychosis Fat emboli Alcohol withdrawal syndrome H. Fat necrosis Intra-abdominal saponification Subcutaneous tissue necrosis source: Reproduced with permission from Greenberger NJ, Toskes PP, Isselbacher KJ: Diseases of the pancreas, in Harrison’s Principles of Internal Medicine, 2nd ed. New York: McGraw-Hill, 1987, p 1373.

plasma have been tested to prevent proteolysis, but with little success. Because a significant component of the patient’s distress arises from the inflammatory aspect of pancreatitis, various methods have been tried to alleviate inflammation, including indomethacin and the prostaglandin inhibitors, but again, these have not proved to be of much value. Some recent studies examined a different strategy, namely the use of platelet-aggregating factor (PAF) antagonists such as PAF acetylhydrolase (PAF-AH) and Lexipafant. These showed promising results in experimental animals and in initial clinical studies, but did not live up to their promise in larger-scale clinical trials.44 The current principles of treatment are physiologic monitoring, metabolic support, and maintenance of fluid balance, which can become dangerously disturbed even in mild acute pancreatitis because of fluid sequestration, vomiting, and sudoresis. Because hypovolemia can result in pancreatic and other visceral ischemia, fluid balance should be assessed at least every 8 hours initially. The severe pain of acute pancreatitis prevents the patient from resting, and results in ongoing cholinergic discharge, which stimulates gastric and pancreatic secretion. Therefore pain management is

of great importance. Administration of buprenorphine, pentazocine, procaine hydrochloride, and meperidine are all of value in controlling abdominal pain. Morphine is to be avoided, due to its potential to cause sphincter of Oddi spasm. Antibiotic therapy has not proved to be of value in the absence of signs or documented sources of infection. Cautious resumption of oral feeding consisting of small and slowly increasing meals is permissible after the abdominal pain and tenderness have subsided, serum amylase has returned to normal, and the patient experiences hunger. This usually occurs within a week of the onset of an attack of mild acute pancreatitis. A low-fat, low-protein diet is advocated as the initial form of nutrition following an attack of acute pancreatitis.

Severe Pancreatitis Pancreatitis can be classified as severe based on predictors such as APACHE-II scores and Ranson’s signs, and any evidence that the condition is severe mandates care of the patient in the intensive care unit. Such evidence may take various forms, such as the onset of encephalopathy, a hematocrit over 50, urine output less than 50 mL/h, hypotension, fever, or peritonitis. Elderly patients with three or more Ranson’s criteria should also be monitored carefully despite the absence of severe pain.45 Patients may develop ARDS, and many patients who die during the early stages of severe acute pancreatitis have this complication. Until recently, the lung injury has been thought to be caused by the systemic release of phospholipase A2 and other enzymes that directly damage alveolar tissue and pulmonary capillaries. In addition, recent evidence implicates the cell adhesion molecule ICAM-1, neutrophils, PAF, substance P, and certain chemokines. The presence of ARDS usually requires assisted ventilation with positive end-expiratory pressure. The value of peritoneal lavage in removing enzyme-rich ascites remains unclear. It has been advocated in patients with deteriorating respiratory function and/or shock that is refractory to maximal management, but its effectiveness in reducing the mortality risk of severe acute pancreatitis remains unproven. Acute pancreatitis may be accompanied by cardiovascular events such as cardiac arrhythmia, myocardial infarction, cardiogenic shock, and congestive heart failure. The conventional modalities of treatment apply in these cases in addition to the support described above.

Infections Infection is a serious complication of acute pancreatitis and is the most common cause of death. It is caused most often by translocated enteric bacteria, and is seen commonly in necrotizing rather than interstitial pancreatitis. If there is an indication of infection (e.g., retroperitoneal air on CT scan), then a CT- or ultrasound-guided fine-needle aspiration should be performed for Gram’s stain and culture of the fluid or tissue, and the indicated antibiotic therapy initiated. However, antibiotics alone may not be effective in infected necrosis, which has a mortality of nearly 50% unless d´ebrided surgically (Fig. 32-15). The long-held opinion that antibiotic prophylaxis in necrotizing pancreatitis is of little use has been altered by recent studies showing a beneficial prophylactic effect with antibiotics such as metronidazole, imipenem, and thirdgeneration cephalosporins.46−48 Because Candida species are common inhabitants of the upper gastrointestinal tract, Candida sepsis

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FIG. 32-15. Operative view of infected acute pancreatitis. Peripancreatic infection, characterized by mucopurulent exudate, extends far beyond the boundaries of the pancreas in the retroperitoneum.

and secondary fungal infection of pancreatic necrosis is a risk in severe disease. The role of empiric therapy with fluconazole in cases of severe acute pancreatitis is currently being investigated in largescale clinical trials.

Sterile Necrosis Patients with sterile necrosis have a far better prognosis than those with infected necrosis, with a reported mortality of near zero in the absence of systemic complications. However, others report mortality rates as high as 38% in patients with a single systemic complication. Treatment of sterile necrotic pancreatitis falls into three degrees of aggressiveness. At one end of the scale is the patient with no systemic complications and no concerns about secondary infections, who can be managed with the supportive care described previously and be cautiously brought back to refeeding. The area of sterile necrosis may evolve into a chronic pseudocyst, or may resolve. An intermediate course is demonstrated by the patient who develops systemic complications, and in whom a secondary infection is suspected. A CT-guided, fine-needle aspiration then confirms or disproves infection, and in the latter instance the patient can be managed medically. The last and most serious condition is that of the patient who appears to be very ill, has high APACHE-II and Ranson’s scores, and shows evidence of systemic toxicity including shock. Patients in this category have a poor chance of survival without aggressive d´ebridement, and a decision may be made to proceed with exploration simply due to a relentless course of deterioration despite maximal medical therapy.43 It must be emphasized that current opinion is against d´ebridement in sterile necrosis unless it is accompanied by life-threatening systemic complications (Fig. 32-16).

Pancreatic Abscess A pancreatic abscess occurs 2 to 6 weeks after the initial attack, in contrast to infected necrosis, which occurs in the first few hours or days. The mechanism of delayed infection is not clear, but

the treatment consists of external drainage, whether established by surgical or by percutaneous catheter-based methods.

Nutritional Support The guiding principle of resting the pancreas dictates that patients with acute pancreatitis not be fed orally until their clinical condition improves. This generally occurs in 3 to 7 days in patients with mild pancreatitis, but the situation in patients with severe pancreatitis is more complicated, requiring nutritional support for several weeks. This can be provided by total parenteral nutrition (TPN) or by enteral nutrition through a jejunal tube.49 There is some debate regarding the preferred route, since TPN is known to result in early atrophy of the gut mucosa, a condition that favors transmigration of luminal bacteria, and intrajejunal feeding still stimulates pancreatic exocrine secretion through the release of enteric hormones. Recent animal studies and preliminary clinical trials on humans suggest that on balance, jejunal feeding may be superior to TPN.

Treatment of Biliary Pancreatitis Gallstones are the most common cause of acute pancreatitis worldwide. Most patients pass the offending gallstone(s) during the early hours of acute pancreatitis, but have additional stones capable of inducing future episodes. This raises the question of the timing of surgical or endoscopic clearance of gallstones. The issue of when to intervene is controversial. Several studies have been aimed at resolving this controversy, but the issue is clouded by the fact that each position is open to some theoretical objection. Additional points of contention include varying inclusion criteria, years of observation of the studied groups, and a lack of uniformity regarding definitions. General consensus favors either urgent intervention (cholecystectomy) within the first 48 to 72 hours of admission, or briefly delayed intervention (after 72 hours, but during the initial hospitalization) to give an inflamed pancreas time to recover. Cholecystectomy and operative common duct clearance is probably the best treatment for otherwise healthy patients with obstructive pancreatitis. However, patients who are at high risk for surgical intervention are best

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

INCIDENCE RATE / 100,000 / YEAR

1240

CONFIRMATION OF DIAGNOSIS Clinical Symptoms Lipase / Amylase Ultrasound

12

ASSESSMENT OF SEVERITY Clinical Signs Scoring Systems CRP, LDH, IL-6, TAP, etc. i.v. Contrast CT Scan

SEVERE

MILD

ICU

Antibiotics

Supportive Care

4

0 1945

1955

1965

1975

1985

1995

YEAR

FIG. 32-17. Incidence of chronic pancreatitis. The reported incidence of chronic pancreatitis has increased steadily over the past 50 years (Reproduced with permission from Worning.53 ).

Necrotizing

Improve

8

FNA

Infection Sepsis

although population studies suggest a prevalence that ranges from 5 to 27 persons per 100,000 population, with considerable geographic variation.51,52 Differences in diagnostic criteria, regional nutrition, alcohol consumption, and medical access account for variations in the frequency of the diagnosis, but the overall incidence of the disease has risen progressively over the past 50 years53 (Fig. 32-17). Autopsy data are difficult to interpret because a number of changes associated with chronic pancreatitis, such as fibrosis, duct ectasia, and acinar atrophy, are also present in asymptomatic elderly patients.54 Although the prevalence of chronic pancreatitis in patients with alcoholic cirrhosis and fatty liver ranges from 9 to 34%, the prevalence of chronic pancreatitis among known alcoholics is only 5 to 15%.53,55,56

Etiology Surgical De´bridment FIG. 32-16. Algorithm for managing acute pancreatitis.

treated by endoscopic sphincterotomy, with clearance of stones by endoscopic retrograde cholangiopancreatography (ERCP). In the case of acute biliary pancreatitis in which chemical studies suggest that the obstruction persists after 24 hours of observation, emergency endoscopic sphincterotomy and stone extraction is indicated. Routine ERCP for examination of the bile duct is discouraged in cases of biliary pancreatitis, as the probability of finding residual stones is low, and the risk of ERCP-induced pancreatitis is significant. Patients who are suspected of harboring a persistent impacted stone in the distal common bile duct or ampulla should have confirmation by radiologic imaging (CT, magnetic resonance cholangiopancreatography, or endoscopic ultrasonography) before intervention.

CHRONIC PANCREATITIS Definition, Incidence, and Prevalence Chronic pancreatitis is an incurable, chronic inflammatory condition that is multifactorial in its etiology, highly variable in its presentation, and a challenge to treat successfully. Autopsy studies indicate the prevalence to be as high as 5% in Scandinavia,50

Worldwide, alcohol consumption and abuse is associated with chronic pancreatitis in up to 70% of cases (Table 32-6). In 1878, Freidreich proposed that “a general chronic interstitial pancreatitis may result from excessive alcoholism (drunkard’s pancreas).”59 Since that observation, numerous studies have shown that a causal relationship exists between alcohol and chronic pancreatitis, but the prevalence of this form of the disease in Western countries ranges widely, from 38 to 94%.53 Other major causes worldwide include tropical (nutritional) and idiopathic disease, as well as hereditary causes.

Alcohol There is a linear relationship between exposure to alcohol and the development of chronic pancreatitis.60 The risk of disease is present in patients with even a low or occasional exposure to alcohol (1 to Table 32-6 Etiology of Chronic Pancreatitis Alcohol, 70% Idiopathic (including tropical), 20% Other, 10% Hereditary Hyperparathyroidism Hypertriglyceridemia Autoimmune pancreatitis Obstruction Trauma Pancreas divisum

32/PANCREAS

20 g/d), so there is no threshold level of alcohol exposure below which there is no risk of developing chronic pancreatitis. Furthermore, although the risk of disease is dose related, and highest in heavy (150 g/d) drinkers, fewer than 15% of confirmed alcohol abusers suffer from chronic pancreatitis.61,62 In a study of 247 patients with fatal acute alcoholic pancreatitis, 53% of patients had no autopsy evidence of chronic pancreatitis.63 However, the duration of alcohol consumption is definitely associated with the development of pancreatic disease. The onset of disease typically occurs between ages 35 to 40, after 16 to 20 years of heavy alcohol consumption. Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years.64,65 Although the pattern of disease presentation is well known in those alcohol users who develop pancreatic disease, the pathophysiology of alcohol-induced pancreatic disease is still an area of active investigation. In their 1946 classic study, Comfort, Gambill, and Baggenstoss proposed that chronic pancreatitis was the result of multiple episodes of acute inflammation, with residual and progressively increasing chronic inflammation.66 Subsequently, other investigators proposed that initial acute inflammation was not necessarily linked to chronic changes in the pancreas,67 and Kondo and associates showed that other, additional factors were necessary for repeated exposure to alcohol to cause chronic pancreatitis.68 Regardless of the requirement for other predisposing or facilitative factors, the concept that multiple episodes (or a prolonged course) of pancreatic injury ultimately leads to chronic disease is widely accepted as the pathophysiologic sequence65 (Fig. 32-18). Laboratory studies in rodents reveal that repeated episodes of acute non–alcohol induced pancreatitis results in findings of chronic pancreatitis,69,70 and the induction of severe acute pancreatitis by a single intraductal infusion of oleic acid reproducibly results in chronic pancreatitis in rats.71 Alcohol-associated chronic pancreatitis is less common in Japan and India, where a there is a lower per capita consumption of alcohol, and its incidence is otherwise quite variable with regard to geography, nutrition, and race.67 Although alcohol exposure to the pancreatic ductal system, or elevated levels of alcohol in the bloodstream, has been shown to alter the integrity and function of pancreatic

DEGREE OF PANCREATIC DAMAGE

NECROSIS-FIBROSIS SEQUENCE

= Episode of Acute Pancreatitis

TIME FIG. 32-18. “Multiple hit” theory of the etiology of acute pancreatitis. Multiple episodes of the acute pancreatitis cause progressively more organized inflammatory changes that ultimately result in chronic inflammation and scarring. (Reproduced with permission from Apte et al.65 ).

1241

ducts and acini directly,72,73 most investigators believe that alcohol metabolites such as acetaldehyde, combined with oxidant injury, result in local parenchymal injury that is preferentially targeted to the pancreas in predisposed individuals. Repeated or severe episodes of toxin-induced injury activate a cascade of cytokines, which in turn induces pancreatic stellate cells to produce collagen and cause fibrosis (Fig. 32-19). It remains to be determined whether alcohol sensitizes the pancreas of susceptible individuals to another cause of acute inflammation, or whether genetic or other factors predispose to direct alcohol-related injury.65 Since the discovery of specific genetic mutations and deletions associated with hereditary pancreatitis (see below), many studies have been undertaken to determine whether specific genetic abnormalities are associated with alcoholic chronic pancreatitis.74 No mutations of the major genetic abnormality associated with hereditary pancreatitis, the catatonic trypsinogen gene or PRSS1,75 have been identified in patients with alcoholic chronic pancreatitis. A second genetic marker for hereditary pancreatitis, the pancreatic secretory trypsin inhibitor, or SPINK1 gene, has also been studied. Mutations in SPINK1 are observed in the general population, and Witt and colleagues found a 5.8% rate of SPINK1 mutations in patients with alcoholic pancreatitis, compared to a 0.8% rate in the control population.76 Studies which have examined some of the known polymorphisms and mutations of the cystic fibrosis transmembrane receptor (CFTR) gene have thus far failed to demonstrate an association with alcoholic chronic pancreatitis. Therefore, a dominant hereditary cofactor for alcoholic pancreatitis remains to be elucidated. Alcohol may interfere with the intracellular transport and discharge of digestive enzymes, and may contribute to the colocalization of digestive enzymes and lysosomal hydrolase within acinar cells, leading to autodigestion77,78 (see section on acute pancreatitis). A high-protein, low-bicarbonate, low-volume secretory output is seen after chronic alcohol exposure,79 which may contribute to the precipitation of proteins in secondary ducts in the early stages of chronic pancreatitis.80 Lithostathine, a protein found in pancreatic juice, inhibits the formation of calcium carbonate crystals,81 and has been found to be decreased in the pancreatic duct fluid in alcoholic and nonalcoholic chronic pancreatitis patients82 (see section on stone formation below). The zymogen membrane-associated protein GP2 is also found in protein precipitates within small ducts, and may contribute to small duct obstruction in chronic pancreatitis.83 Calcium is complexed to protein plugs in small ductules, secondary ducts, and eventually in the main ductal system, which causes ductal cell injury and obstruction of the secretory system, which further promotes an inflammatory response. Cigarette smoking has been strongly associated with chronic pancreatitis and with the development of calcific pancreatitis.84 Studies on the role of smoking in the development of alcoholic pancreatitis have been conflicting, although the risk of cancer in chronic pancreatitis is increased significantly by smoking. In hereditary pancreatitis smoking has been found to lower the age of onset of carcinoma by about 20 years.85 Smoking would therefore appear to be a definite risk factor for the late complications of alcoholic pancreatitis, if not an early cofactor.

Hyperparathyroidism Hypercalcemia is a known cause of pancreatic hypersecretion,104 and chronic hypercalcemia caused by untreated hyperparathyroidism is associated with chronic calcific pancreatitis.105 Hypercalcemia is also a stimulant for pancreatic calcium secretion, which

1242

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

PATHOGENESIS OF ALCOHOLIC PANCREATIC FIBROSIS Ethanol

Toxic Metabolites

Cytokines

Autodigestion

Pancreatic Necrosis

Stellate Cell Activation

Pancreatic Fibrosis

Oxident Stress

FIG. 32-19. Chemical pathogenesis of fibrosis in chronic pancreatitis. The relationship of cytokine release to the activation of pancreatic stellate cells (PSCs) illustrates pathways that are potential targets for therapeutic intervention.

contributes to calculus formation and obstructive pancreatopathy. The treatment is correction of the hyperparathyroidism and assessment of any additional endocrinopathies.

the formation of stone disease. The clinician should therefore avoid the assumption that calcific pancreatitis confirms the diagnosis of alcohol abuse.

Hyperlipidemia

Chronic Obstructive Pancreatitis. This refers to chronic inflammatory changes which are caused by the compression or occlusion of the proximal ductal system by tumor, gallstone, posttraumatic scar, or inadequate duct caliber (as in pancreas divisum). In this category, the chronic pancreatitis may be clinically silent or present with exocrine or endocrine insufficiency, and the distribution of changes within the gland are uniformly distributed distal to the causative process.

In addition to the risk of acute pancreatitis, hyperlipidemia and hypertriglyceridemia predispose women to chronic pancreatitis when they receive estrogen replacement therapy.106 Fasting triglyceride levels less than 300 mg/dL are below the threshold for this to occur, and the mechanism of estrogen potentiation of hyperlipidemia-induced chronic pancreatitis is unknown. It is assumed that chronic changes occur after repeated subclinical episodes of acute inflammation. Aggressive therapy of hyperlipidemia is therefore important in peri- or postmenopausal patients who are candidates for estrogen therapy.

Classification A major impediment to an accurate accounting of the frequency and severity of chronic pancreatitis has been the difficulty with which investigators and clinicians have struggled to identify a useful classification system. Multiple classification systems have been proposed. In 1963, Henri Sarles organized a symposium in Marceilles, France, and subsequent symposia were held in Cambridge (1983), Marseilles (1984), and Rome (1998). A current classification system, as delineated by Singer and Chari, is shown in Table 32-7.57

Chronic Calcifying (Lithogenic) Pancreatitis. This type is the largest subgroup in the current classification scheme, and includes patients with calcific pancreatitis of most etiologies. Although the majority of patients with calcific pancreatitis have a history of alcohol abuse, stone formation and parenchymal calcification can develop in a variety of etiologic subgroups; hereditary pancreatitis and tropical pancreatitis are particularly noteworthy for

Chronic Inflammatory Pancreatitis. This type is characterized by diffuse fibrosis and a loss of acinar elements with a predominant mononuclear cell infiltration throughout the gland. Chronic Autoimmune Pancreatitis. This type is associated with a variety of illnesses with suspected or proven autoimmune etiology, such as Sj¨ogren’s syndrome. Asymptomatic Pancreatic Fibrosis. This type is seen in some asymptomatic elderly patients, in tropical populations, or in asymptomatic alcohol users. There is diffuse perilobar fibrosis and a loss of acinar cell mass, but without a main ductular component. A shortcoming of these clinical classification systems is the lack of histologic criteria of chronic inflammation, due to the usual absence of a biopsy specimen. The differentiation of recurrent acute pancreatitis from chronic pancreatitis with exacerbations of pain can be difficult to establish, and is not facilitated by the current system. Similarly, cystic fibrosis is known to cause fibrosis and acinar dysfunction, but is not included in the classification despite increasing evidence for its possible role in idiopathic chronic pancreatitis.58 Therefore further refinements in the classification system for chronic pancreatitis are needed to allow a better prediction of its clinical course and a more accurate diagnosis of a likely etiologic agent.

Table 32-7 Classification of Chronic Pancreatitis Chronic Calcific Pancreatitis

Chronic Obstructive Pancreatitis

Chronic Inflammatory Pancreatitis

Chronic Autoimmune Pancreatitis

Asymptomatic Pancreatic Fibrosis

Alcohol Hereditary Tropical Hyperlipidemia Hypercalcemia Drug-induced Idiopathic

Pancreatic tumors Ductal stricture Gallstone- or trauma-induced Pancreas divisum

Unknown

Associated with autoimmune disorders (e.g., primary sclerosing cholangitis) Sj¨ogren’s syndrome Primary biliary cirrhosis

Chronic alcoholic Endemic in asymptomatic residents in tropical climates

source: Reproduced with permission from Singer et al.57

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Tropical (Nutritional) Pancreatitis. Tropical chronic pancreatitis is highly prevalent among adolescents and young adults raised in Indonesia, southern India, and tropical Africa.86 Abdominal pain develops in adolescence, followed by the development of a brittle form of pancreatogenic diabetes. Parenchymal and intraductal calcifications are seen, and the pancreatic duct stones may be quite large.87 Many of the patients appear malnourished, some present with extreme emaciation, and a characteristic cyanotic coloration of the lips may be seen.88 In addition to protein-caloric malnutrition, toxic products of some indigenous foodstuffs may also contribute to the disease. Cassava root is a starch (the origin of tapioca) which is a staple in the diet throughout the Afro-Asian region where tropical pancreatitis is prevalent. Cassava contains toxic glycosides, which form hydrocyanic acid when mixed with (gastric) hydrochloric acid.89 Hydrocyanic acid is reduced to thiocyanate, which blocks a variety of enzymes, including superoxide dismutase. The simultaneous deficiency of dietary trace elements such as zinc, copper, and selenium could retard the detoxification of cyanogens, and result in an increased susceptibility to free radical injury of the pancreas. Clinically, tropical pancreatitis presents much like hereditary pancreatitis, and a familial pattern among cases is not unusual. Recently an association with mutations of the pancreatic secretory trypsin inhibitor (PSTI) or SPINK1 gene in patients with tropical pancreatitis has been reported.90,91 The accelerated deterioration of endocrine and exocrine function, the chronic pain due to obstructive disease, and the recurrence of symptoms despite decompressive procedures characterize the course of disease.88 As immigrants from the tropical regions increasingly find their way to all parts of the world, an awareness of this severe form of chronic pancreatitis is helpful for those who treat patients with pancreatic disease. Hereditary Pancreatitis. In 1952, Comfort and Steinberg reported a kindred of “hereditary chronic relapsing pancreatitis” after treating the proband, a 24-year-old woman, at the Mayo Clinic.92 Subsequently, familial patterns of chronic, nonalcoholic pancreatitis have been described worldwide, and a familiar pattern has emerged. Typically, patients first present in childhood or adolescence with abdominal pain, and are found to have chronic calcific pancreatitis on imaging studies. Progressive pancreatic dysfunction is common, and many patients present with symptoms due to pancreatic duct obstruction. The risk of subsequent carcinoma formation is increased, reaching a prevalence in some series of 40%, but the age of onset for carcinoma is typically over 50 years.93,94 The disorder is characterized by an autosomal dominant pattern of inheritance, with 80% penetrance and variable expression. The incidence is equal in both sexes. Whitcomb and colleagues,95 and separately LeBodic and associates,96 performed gene linkage analysis and identified a linkage for hereditary pancreatitis to chromosome 7q35. Subsequently, the region was sequenced, and revealed eight trypsinogen genes. Mutational analysis revealed a missense mutation resulting in an Arg to His substitution at position 117 of the cationic trypsinogen gene, or PRSS1, one of the primary sites for proteolysis of trypsin. This mutation prevents trypsin from being inactivated by itself or other proteases, and results in persistent and uncontrolled proteolytic activity and autodestruction within the pancreas.97 The position 117 mutation of PRSS1 and an additional mutation, now known collectively as the R122H and N291 mutations of PRSS1, account for about two thirds of cases of hereditary pancreatitis. Recently, Schneider and Whitcomb described a probable mutation in the anionic trypsinogen gene which may also be present in some cases.98 Thus, hereditary pancreatitis results from one or more mutational

1243

defects which incapacitate an autoprotective process that normally prevents proteolysis within the pancreas. Similarly, PSTI, also known as SPINK1, has been found to have a role in hereditary pancreatitis.76 SPINK1 specifically inhibits trypsin action by competitively blocking the active site of the enzyme. Witt and colleagues investigated 96 unrelated children with chronic pancreatitis in Germany and found a variety of SPINK1 mutations in 23% of the patients.76 Several studies have now confirmed an association of SPINK1 mutations with familial and idiopathic forms of chronic pancreatitis, as well as tropical pancreatitis.90,92,99,100 SPINK1 mutations are common in the general population as well, and the frequency of these mutations varies in different cohorts of idiopathic chronic pancreatitis, from 6.4% in France101 to 25.8% in the U.S.99 The cystic fibrosis transmembrane receptor (CFTR) gene contains over 4300 nucleotides, divided into 24 exons, which encode for a 1480-amino acid protein. Over 1000 polymorphisms have been reported, and many are common.74 The severe CFTR mutation associated with the classic disease, F508, is rarely observed in chronic pancreatitis. But other minor CFTR mutations have been noted to be associated with chronic idiopathic pancreatitis in which the pulmonary, intestinal, and cutaneous manifestations of the disease are silent.102,103 It is likely that many of the “idiopathic” forms of chronic pancreatitis, as well as some patients with the more common forms of the disease, will be found to have a genetic linkage or predisposition. The goal of this active area of research is to elucidate specific molecular abnormalities, and provide strategies for treatment and prevention.

Autoimmune Pancreatitis. A variant of chronic pancreatitis is a nonobstructive, diffusely infiltrative disease associated with fibrosis, a mononuclear cell (lymphocyte, plasma cell, or eosinophil) infiltrate, and an increased titer of one or more autoantibodies.107 Compressive stenosis of the intrapancreatic portion of the common bile duct is frequently seen, along with symptoms of obstructive jaundice. Increased levels of serum beta-globulin or immunoglobulin G are also present. Steroid therapy is uniformly successful in ameliorating the disease, including any associated bile duct compression.108 The differential diagnosis includes lymphoma, plasmacytoma (“pseudotumor” of the pancreas), and diffuse infiltrative carcinoma. Although the diagnosis is confirmed on pancreatic biopsy, presumptive treatment with steroids is usually undertaken, especially when clinical and laboratory findings support the diagnosis. Failure to obtain a cytologic specimen may lead to an unnecessary resectional procedure, and an untreated inflammatory component may cause sclerosis of the extrahepatic or intrahepatic bile ducts, with eventual liver failure.109 Chronic Obstructive Pancreatitis. Obstruction of the main pancreatic duct by inflammatory (posttraumatic) or neoplastic processes, including pseudocysts, intraductal mucin-secreting tumors, and ampullary and pancreatic tumors, can result in a form of chronic pancreatitis associated with diffuse fibrosis, dilated main and secondary pancreatic ducts, and acinar atrophy. The patient may have little in the way of pain symptoms, or may present with signs of exocrine insufficiency. Intraductal stone formation is rare, and both functional and structural abnormalities may improve when the obstructive process is relieved or removed. Trauma to the pancreas frequently results in duct injury and leakage, which may result in pseudocyst formation as well as local scar formation. Inadequately treated pancreatic trauma may result in persistent inflammatory changes in the distal gland.110

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

DUCT VARIATIONS NORMAL: With Duct of Santorini

NORMAL: Without Duct of SantorinI

FUNCTIONAL PANCREAS DIVISUM: Filamentous Communication between Dorsal and Ventral Ducts

for regulatory proteins in the pancreas. In addition, the idiopathic group has included a large number of older patients for whom no obvious cause of recurrent or chronic pancreatitis can be found.115 However, because the prevalence of biliary calculi increases steadily with age, it is not surprising that as methods to detect biliary stone disease and microlithiasis have improved, a larger proportion of elderly “idiopathic” pancreatitis patients are found to have biliary tract disease.116 As noted in the section on hereditary pancreatitis above, an increasing number of mutations of the CFTR and SPINK1 genes have been identified in association with idiopathic pancreatitis.101−103 However, the role of genetic analysis in the management of these patients remains unclear, as guidelines have yet to be developed to allow physicians to use the data consistently. The clinical management of patients who harbor a minor CFTR mutation and chronic pancreatitis, for example, is still dictated by the manifestations of the pancreatitis. Any genetic counseling for the patient and his or her family has yet to be defined.117

Pathology Histology

PANCREAS DIVISUM: Small Duct of Wirsung

PANCREAS DIVISUM: No Duct of Wirsung (Only Dorsal Duct)

FIG. 32-20. Pancreas divisum. Normal pancreatic duct anatomy and the variations of partial or complete pancreas divisum are shown. (Reproduced with permission from Warshaw.112 )

Pancreas divisum represents a special case of obstructive pancreatitis. It is the most common congenital anomaly involving the pancreas and occurs in up to 10% of children. It is thought to predispose the pancreas to recurrent acute pancreatitis and chronic pancreatitis, due to functional obstruction of a diminutive duct of Santorini which fails to communicate with Wirsung’s duct (Fig. 32-20). However, the classic picture of obstructive pancreatopathy with a dilated dorsal duct is unusual in pancreas divisum, so a decompressive operation or a lesser papilla sphincteroplasty is frequently not feasible or unsuccessful. Endoscopic stenting through the lesser papilla may result in temporary relief of symptoms, and this response would increase the possibility that a permanent surgical or endoscopic intervention will be successful. Although some authors emphasize the pathologic implications of pancreas divisum,111,112 others express skepticism that it represents a true risk to pancreatic secretory capacity or contributes to the development of chronic pancreatitis.113,114

Idiopathic Pancreatitis. When a definable cause for chronic pancreatitis is lacking, the term “idiopathic” is used to categorize the illness. Not surprisingly, as diagnostic methods and clinical awareness of disease improve, fewer patients fall into the idiopathic category. Classically, the idiopathic group includes young adults and adolescents who lack a family history of pancreatitis, but who may represent individuals with spontaneous gene mutations encoding

In early chronic pancreatitis, the histologic changes are unevenly distributed, and are characterized by induration, nodular scarring, and lobular regions of fibrosis (Fig. 32-21). As the disease progresses, there is a loss of normal lobulation, with thicker sheets of fibrosis surrounding a reduced acinar cell mass, and dilatation of ductular structures (Fig. 32-22). The ductular epithelium is usually atypical, and may display features of dysplasia, as evidenced by cuboidal cells with hyperplastic features, accompanied by areas of mononuclear cell infiltrates or patchy areas of necrosis. Cystic changes may be seen, but areas of relatively intact acinar elements and normal-appearing islets persist. In severe chronic pancreatitis, there is considerable replacement of acinar tissue by broad, coalescing areas of fibrosis, and the islet size and number are reduced (Fig. 32-23). Small arteries appear thickened and neural trunks become prominent.118 Tropical pancreatitis and hereditary pancreatitis are histologically indistinguishable from chronic alcoholic pancreatitis. In obstructive chronic pancreatitis, calculi are absent, although periacinar fibrosis and dilated ductular structures are prominent. In pancreatic lobular fibrosis seen in elderly subjects, small ducts are dilated, sometimes with small calculi trapped within. Hypertrophy of ductular epithelia is thought to cause this small-duct disease, which is accompanied by perilobular fibrosis.119

Fibrosis A common feature of all forms of chronic pancreatitis is the perilobular fibrosis that forms surrounding individual acini, then propagates to surround small lobules, and eventually coalesces to replace larger areas of acinar tissue. The pathogenesis of this process involves the activation of pancreatic stellate cells (PSCs) that are found adjacent to acini and small arteries.120 The extended cytoplasmic processes of PSCs encircle the acini, but appear quiescent in the normal gland, where they contain lipid vacuoles and cytoskeletal proteins. In response to pancreatic injury, the PSCs become activated and proliferate (similarly to hepatic stellate cells), lose their lipid vesicles, and transform into myofibroblast-like cells. These cells respond to proliferative factors such as transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and proinflammatory cytokines, and synthesize and secrete type I and III collagen and fibronectin. Recent studies indicate that vitamin A metabolites,

32/PANCREAS

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FIG. 32-21. Histology of early chronic pancreatitis. High-power microscopic (400x) histology of chronic pancreatitis shows an infiltration of mononuclear inflammatory cells throughout the interstitium of the pancreas, with little fibrosis. (Courtesy of Dr. Rhonda Yantiss, Department of Pathology, University of Massachusetts Medical School.)

similar to those present in quiescent PSCs, can inhibit the collagen production of activated cultured PSCs.121 This raises the possibility that early intervention may be possible to interrupt or prevent the fibrosis resulting from ongoing activation of PSCs. The overall pathogenic sequence proposed by Schneider and Whitcomb122 whereby alcohol induces acute pancreatitis, and with ongoing exposure promotes the development of chronic fibrosis, is summarized in Fig. 32-24. Stellate cells surrounding the acinus are activated in acute pancreatitis, but may be inactivated by antiinflammatory cytokines, and in the absence of further injury may revert to a quiescent state. The role of proinflammatory macrophages, FIG. 32-22. Gross appearance of chronic pancreatitis. Areas of fibrosis and scarring are seen adjacent to other areas within the gland in which the lobar architecture is grossly preserved. A dilated pancreatic duct indicates the presence of downstream obstruction in this specimen removed from a patient with chronic pancreatitis. (Courtesy of Dr. Rhonda Yantiss, Department of Pathology, University of Massachusetts Medical School.)

cytokines, and stellate cells in models of acute and chronic pancreatitis represent an important area of current research.

Stone Formation Pancreatic stones are composed largely of calcium carbonate crystals trapped in a matrix of fibrillar and other material.123 The fibrillar center of most stones contains no calcium, but a mixture of other metals. This suggests that stones form from an initial noncalcified protein precipitate, which serves as a focus for layered calcium carbonate precipitation. The same low-molecular-weight protein is

1246

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

FIG. 32-23. Histology of severe chronic pancreatitis. High-power microscopic (400x) histologic appearance of advanced chronic pancreatitis shows extensive sheets of fibrosis and loss of acinar tissue, with preservation of islet tissue in scattered areas. (Courtesy of Dr. Rhonda Yantiss, Department of Pathology, University of Massachusetts Medical School.)

present in stones and protein plugs, and was initially named pancreatic stone protein, or PSP.124 PSP comprises up to 14% of the protein content of mammalian pancreatic juice, and is secreted in four isoforms (PSP-S2, S3, S4, and S5), with molecular weights ranging from 16 to 20 kd. PSP was found to be a potent inhibitor of calcium carbonate crystal growth, and has subsequently been renamed lithostathine.125 Independently, a 15-kd fibrillar protein isolated from the pancreas was named pancreatic thread protein, or PTP, and it has been shown to be homologous with lithostathine. Finally, a protein product of the reg gene, so named because it is expressed in association with regenerating islets in models of pancreatic injury, was isolated and called reg protein.126 This also has been found to be homologous with lithostathine.127 No overall homology has been found between lithostathine and other pancreatic proteins. The PSP/PTP/reg/lithostathine gene encodes for a 166-amino acid product that undergoes posttranslational modification to the S2 through S5 isoforms present in pancreatic juice. The protein is expressed in all rodents and mammals, both in the pancreas as well as in brain tissue, where it is found in particularly high concentrations in pyramidal neurons in Alzheimer’s disease and Down’s syndrome. It is also found in the renal tubules, which is consistent with its biologic action of preventing calcium carbonate precipitation.127 Calcium and bicarbonate ions are normally present in pancreatic juice in high concentration, and the solubility product of calcium carbonate is greatly exceeded under normal conditions. Microcrystals of calcium carbonate can be seen in normal pancreatic juice, but are usually clinically silent. Lithostathine is a potent inhibitor of calcium carbonate crystal formation, at a concentration of only 0.1 µmol/L. However, lithostathine concentrations in normal pancreatic juice are in the range of 20 to 25 µmol/L, so a constant suppression of calcium carbonate crystal formation is present in the normal pancreas. In alcoholics and in patients with alcoholic chronic pancreatitis, lithostathine expression and secretion are dramatically inhibited127−129 (Fig. 32-25). In addition, elevated levels of precipitated lithostathine in the duct fluid in chronic pancreatitis patients

suggests that the availability of the protein may be further reduced by the action of increased proteases and other proteins present in the duct fluid of alcoholic patients. Increased pancreatic juice protein levels in alcoholic men are reversible by abstinence from alcohol,130 so the availability and effectiveness of lithostathine may be restored in patients with early-stage disease by timely intervention. Nevertheless, calcific stone formation represents an advanced stage of disease, which can further promote injury or symptoms due to mechanical damage to duct epithelium or obstruction of the ductular network.

Duct Distortion Although calcific stone disease is normally a marker for an advanced stage of disease, parenchymal and ductular calcifications do not always correlate with symptoms. Obstructing main duct stones are commonly observed and are thought to be an indication for endoscopic or surgical removal. The ball-valve effect of a stone in a secreting system produces inevitable episodes of duct obstruction, usually accompanied by pain. But some patients with complete duct obstruction have prolonged periods of painlessness. Ductular hypertension has been documented in patients with proximal stenosis of the main pancreatic duct, and prolonged ductular distention after secretin administration is taken as a sign of ductular obstruction.131 Although calculus disease and duct enlargement appear together as late stages of chronic pancreatitis, controversy persists over whether they are associated, are independent events, or are causally related.

Radiology Radiologic imaging of chronic pancreatitis assists in four areas: (1) diagnosis, (2) the evaluation of severity of disease, (3) detection of complications, and (4) assistance in determining treatment options.132 With the advent of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), the contour, content, ductal pattern, calcifications, calculi, and cystic disease of the pancreas are all readily discernible.

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SAPE HYPOTHESIS NORMAL:

NORMAL PANCREAS

Alcohol

Cytokines

Metabolic / Oxidative Stress Sentinal Event Stellate Cells (Inactive)

Acinar Cell Injury (+ / − Necrosis)

INFLAMMATORY RESPONSE: PRO-INFLAMMATORY (EARLY)

EARLY ACUTE PANCREATITIS: Necrosis Macrophage

Lymphocyte Neutrophil

ANTI-INFLAMMATORY (LATER)

LATE ACUTE PANCREATITIS:

x = Stress, ETOH x

Collagen, etc. M (Antiinflammatory)

x

x x

x x

Alcohol Metabolic / Oxidative Stress

x

Stellate Cell (Active)

Recurrent Acute Pancreatitis (RAP)

Stress RAP

Anti-Inflammatory NORMAL (RECOVERED):

CHRONIC PANCREATITIS: x x

HEALED

FIBROSIS

x x x

Fibrosis FIG. 32-24. The sentinel acute pancreatitis event (SAPE) hypothesis for the development of chronic pancreatitis. A critical episode of acute pancreatitis activates cytokine-induced transformation of pancreatic stellate cells (PSCs), which results in collagen production and fibrosis. (Reproduced with permission from Whitcomb.97 )

µg LITHOSTATHINE / mg TOTAL PROTEIN

1248

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

30

20

10

0 CCP

Alc.

OPD

Controls

FIG. 32-25. Lithostathine levels in chronic calcific pancreatitis (CCP) patients, patients with alcohol abuse (ALC), patients with other pancreatic disease (OPD), and controls. (Reproduced with permission from Goggin et al.127 )

Transabdominal ultrasonography is frequently used as a screening method for patients with abdominal symptoms or trauma, and the extension of ultrasonic imaging to include endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS) have resulted in the highest-resolution images that are capable of detecting very small ( norepinephrine >> isoproterenol; for β1 receptors: isoproterenol > epinephrine = norepinephrine; and for β2 receptors: isoproterenol > epinephrine >> norepinephrine.

DISORDERS OF THE ADRENAL CORTEX Hyperaldosteronism (Conn’s Syndrome) Hyperaldosteronism may be secondary to stimulation of the renin– angiotensin system from renal artery stenosis and to low-flow states such as congestive heart failure and cirrhosis. Hyperaldosteronism resulting from these conditions is reversible by treatment of the underlying cause. Primary hyperaldosteronism results from autonomous aldosterone secretion, which, in turn, leads to suppression

of renin secretion. Primary aldosteronism usually occurs in individuals between the ages of 30 and 50 years and accounts for 1% of cases of hypertension. Primary hyperaldosteronism is usually associated with hypokalemia; however, more patients with Conn’s syndrome are being diagnosed with normal potassium levels. Most cases result from a solitary functioning adrenal adenoma (approximately 70%) and idiopathic bilateral hyperplasia (30%). Adrenocortical

Table 37-16 Catecholamine Hormone Receptors and the Effects They Mediate Receptor

Tissue

Function

α1

Blood vessels Gut

Contraction Decreased motility, increased sphincter tone Decreased insulin and glucagon release Glycogenolysis, gluconeogenesis Pupil dilation Contraction Sweating Inhibits norepinephrine release Aggregation Chronotropic, inotropic Lipolysis Decreased motility, increased sphincter tone Increased insulin and glucagon release Vasodilation Dilation Relaxation

Pancreas

α2 β1

Liver Eyes Uterus Skin Synapse (sympathetic) Platelet Heart Adipose tissue Gut Pancreas

β2

Blood vessels Bronchioles Uterus

1454

SCHWARTZ’S PRINCIPLES OF SURGERY/BASIC CONSIDERATIONS

carcinoma and glucocorticoid suppressible hyperaldosteronism are rare, each accounting for less than 1% of cases.81 Glucocorticoidsuppressible hyperaldosteronism is an autosomal dominant form of hypertension in which aldosterone secretion is abnormally regulated by ACTH. This condition is caused by recombinations between linked genes encoding closely related isozymes, 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2), and generating a dysregulated chimeric gene with aldosterone synthase activity.82

Symptoms and Signs Patients typically present with hypertension, which is longstanding, moderate to severe, and may be difficult to control despite multiple-drug therapy. Some authors report that patients may be hypertensive for a mean of 7 to 11 years prior to diagnosis. Other symptoms include muscle weakness, polydipsia, polyuria, nocturia, headaches, and fatigue. Weakness and fatigue are related to the presence of hypokalemia

CT SCAN OR MRI

Unilateral adrenal tumor usually 0.5 - 2 cm in diameter

1) Selective venous catheterization for aldosterone and cortisol

Diagnostic Studies

OR

Laboratory Studies. Hypokalemia is a common finding and hyperaldosteronism must be suspected in any hypertensive patient who presents with coexisting spontaneous hypokalemia (K 5 cm) lesions. The patient is placed in the prone-jackknife position and the operating table is flexed at the waist to open the space between the posterior costal margin and the pelvis. Palpation is used to identify the position of the twelfth rib. Percutaneous ultrasound is performed to determine the outline of the underlying kidney and adrenal. When done laparoscopically, the surgeon stands on the side of the adrenal to be removed and the assistant stands on the opposite side. A 1.5-cm incision is placed 2 cm inferior and parallel to the twelfth rib, laterally at the level of the inferior pole of the kidney. Gerota’s space is entered under direct vision by using a 12-mm direct-viewing trocar with a zero-degree laparoscope through the muscle layers of the posterior abdominal wall. Alternatively, blunt dissection with the surgeon’s finger also can identify the space behind Gerota’s fascia. The trocar is then replaced by a dissecting balloon, which is manually inflated using a hand pump under direct vision through the laparoscope. A 12-mm trocar is then reinserted into this space and carbon dioxide is insufflated to 12 to 15 mm Hg pressure. The zerodegree laparoscope is replaced by a 45-degree laparoscope. Two additional 5- or 10-mm trocars are placed, one each on either side of the first port. Laparoscopic ultrasound is then used to help locate the adrenal gland and vessels. The adrenal dissection is begun at the superior pole and then proceeds to the lateral and inferior aspect. The medial dissection is usually performed last and the vessels are identified and divided as described in the previous section.

Pancreas

Open Adrenalectomy

B FIG. 37-68. Technique of laparoscopic adrenalectomy. Exposure of the right adrenal is facilitated by division of the triangular ligament ( A ) and dissection and reflection of the spleen and tail of the pancreas aids in identifying the left adrenal ( B ).

Open adrenalectomy may be performed via four approaches, each with specific advantages and disadvantages. The anterior approach allows examination of the abdominal cavity and resection of bilateral tumors via a single incision. The posterior approach avoids the morbidity of a laparotomy incision, especially in patients with cardiopulmonary disease and those prone to wound complications (Cushing’s syndrome) and avoids abdominal adhesions in patients who have undergone previous abdominal surgery. Recovery time is also quicker and hospitalization shorter. However, the retroperitoneal

37/THYROID, PARATHYROID, AND ADRENAL

1467

exposure is difficult, particularly in obese patients and the small working space makes it unsuitable for tumors greater than 6 cm in diameter. The lateral approach is best for obese patients and for large tumors because it provides a bigger working space. The thoracoabdominal approach is most useful for en bloc resection of large (>10 cm), malignant lesions. However, it is associated with significant morbidity and should be used selectively.

Anterior Approach The adrenals may be removed via a midline incision or bilateral subcostal incision (Fig. 37-69). The former allows adequate infraumbilical exposure for examination of extra-adrenal tumors, whereas the latter provides better superior and lateral exposure. For the right side, the hepatic flexure of the colon is mobilized inferiorly, the triangular ligament is incised to retract the liver, and a Kocher maneuver is used to mobilize the duodenum anteriorly and expose the adrenal gland and the inferior vena cava (Fig. 37-70A). Gerota’s fascia is incised and the gland is freed of surrounding fibrofatty tissue. The lateral and superior surfaces are usually mobilized first. Then, the short, right adrenal vein is dissected, ligated, and divided, taking care not to injure the hepatic veins and inferior vena cava.

Pancreas

Right adrenal

A Colon

Left adrenal v.

Left kidney

Spleen

A

Anterior approach

B

Posterior approach

Pancreas

B FIG. 37-70. Technique of open adrenalectomy: A . Exposure of the right adrenal is facilitated by a Kocher maneuver to mobilize the duodenum and upward retraction of the liver. B . The left adrenal can be exposed by medial visceral rotation of the spleen and pancreas.

On the left side, the adrenal is located cephalad to the pancreatic tail and just lateral to the aorta. For large tumors, the adrenal is best approached by medial visceral rotation to mobilize the spleen, colon, and pancreas toward the midline (see Fig. 37-70B). An alternative approach is to enter the lesser sac by division of the gastrocolic ligament. The pancreas is mobilized superiorly by incision of its inferior peritoneal attachments, thus exposing the left kidney and adrenal. The gland is then mobilized as on the right side.

C

Thoracoabdominal approach

FIG. 37-69. Incisions for open adrenalectomy: anterior approach ( A ), posterior approach ( B ), and thoracoabdominal approach (C ).

Posterior Approach The patient is placed prone on the operating table, similar to the laparoscopic approach. A hockey stick or curvilinear incision may be used, and extended through the latissimus dorsi and sacrospinous

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SCHWARTZ’S PRINCIPLES OF SURGERY/BASIC CONSIDERATIONS

fascia. The twelfth rib is generally excised at its base and the eleventh rib is retracted superiorly to reveal the pleura and the lateral arcuate ligament of the liver on the right side. The pleura is also mobilized cephalad and the adrenal and kidney are identified. The superior aspect of the gland is dissected first, and the superior vessels are identified and ligated. This prevents superior retraction of the adrenal gland. The remainder of the gland is then dissected and the adrenal gland and tumor removed. The resulting space is generally filled with perinephric fat and closed in layers. If the pleura is entered, a red-rubber catheter may be placed in the chest and removed after a Valsalva maneuver, once the chest is closed. If structural lung injury has occurred, a chest tube is needed. After closure of the muscle layers, the patient is given positive pressure and the catheter is removed. A chest x-ray is obtained postoperatively to rule out a pneumothorax.

Lateral Approach The patient is placed in a lateral position with the table flexed and an incision is made between the eleventh and twelfth ribs or subcostally. The dissection is then done as indicated previously.

Complications of Adrenal Surgery General complications associated with laparoscopic adrenalectomy include wound and infection, urinary tract infections, and deep vein thrombosis. Patients with Cushing’s syndrome are more prone to infectious (incisional and intra-abdominal abscess) and thrombotic complications. Specific complications arising from the creation of pneumoperitoneum include injury to various organs from Veress needle and trocar insertion, subcutaneous emphysema, pneumothorax, and hemodynamic compromise. Excessive retraction and dissection may lead to bleeding from injury to the inferior vena cava and renal vessels, or from injury to surrounding organs, such as the liver, pancreas, spleen, and stomach. Postoperative hemodynamic instability may be evident in patients with pheochromocytomas and patients are at risk of adrenal insufficiency after bilateral adrenalectomy and sometimes after unilateral adrenalectomy (unrecognized Cushing’s syndrome or, very rarely, Conn’s syndrome). Long-term morbidity results mainly from injury to nerve roots during trocar insertion, which can lead to chronic pain syndromes or muscle weakness, although this is more of an issue in case of open procedures. Approximately 30% of patients who undergo bilateral adrenalectomy for Cushing’s disease are at risk of developing Nelson’s syndrome from progressive growth of the preexisting pituitary tumor. This leads to increased ACTH levels, hyperpigmentation, visual field defects, headaches, and extraocular muscle palsies. Transsphenoidal pituitary resection is the initial mode of therapy,100 and external beam radiotherapy is used in patients with residual tumor or extrasellar invasion. References 1. Dedivitis RA, Camargo DL, Peixoto GL, et al: Thyroglossal duct: A review of 55 cases. J Am Coll Surg 194:274, 2002. 2. Pisanu A, Pili S, Uccheddu A: Non-recurrent inferior laryngeal nerve. Chir Ital 54:7, 2002. 3. Cernea CR, Ferraz AR, Nishio S, et al: Surgical anatomy of the external branch of the superior laryngeal nerve. Head Neck 14:380, 1992. 4. Kopp P: Pendred’s syndrome and genetic defects in thyroid hormone synthesis. Rev Endocr Metab Disord 1:109, 2000. 5. Yoshida A, Taniguchi S, Hisatome I, et al: Pendrin is an iodide-specific apical porter responsible for iodide efflux from thyroid cells. J Clin Endocrinol Metab 87:3356, 2002.

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37/THYROID, PARATHYROID, AND ADRENAL 33. Cady B, Sedgwick CE, Meissner WA, et al: Risk factor analysis in differentiated thyroid cancer. Cancer 43:810, 1979. 34. Mazzaferri EL, Jhiang SM: Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 97:418, 1994. 35. Hay ID, Grant CS, Bergstralh EJ, et al: Unilateral total lobectomy: Is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124:958, 1998. 36. Mazzaferri EL, Massoll N: Management of papillary and follicular (differentiated) thyroid cancer: New paradigms using recombinant human thyrotropin. Endocr Relat Cancer 9:227, 2002. 37. Sivanandan R, Soo KC: Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid. Br J Surg 88:1241, 2001. 38. Haigh PI: Follicular thyroid carcinoma. Curr Treat Options Oncol 3:349, 2002. 39. Thompson LD, Wieneke JA, Paal E, et al: A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature. Cancer 91:505, 2001. 40. Lopez-Penabad L, Chiu AC, Hoff AO, et al: Prognostic factors in patients with H¨urthle cell neoplasms of the thyroid. Cancer 97:1186, 2003. 41. Mazzaferri EL, Robbins RJ, Spencer CA, et al: A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 88:1433, 2003. 42. Kim TH, Yang DS, Jung KY, et al: Value of external irradiation for locally advanced papillary thyroid cancer. Int J Radiat Oncol Biol Phys 55:1006, 2003. 43. Clayman GL, el-Baradie TS: Medullary thyroid cancer. Otolaryngol Clin North Am 36:91, 2003. 44. Brandi ML, Gagel RF, Angeli A, et al: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658, 2001. 45. Pasieka JL: Anaplastic thyroid cancer. Curr Opin Oncol 15:78, 2003. 46. Giuffrida D, Ferrau F, Pappalardo A, et al: Metastasis to the thyroid gland: A case report and review of the literature. J Endocrinol Invest 26:560, 2003. 47. Hedayati N, McHenry CR: The clinical presentation and operative management of nodular and diffuse substernal thyroid disease. Am Surg 68:245, 2002. 48. Fewins J, Simpson CB, Miller FR: Complications of thyroid and parathyroid surgery. Otolaryngol Clin North Am 36:189, 2003. 49. Akerstrom G, Malmaeus J, Bergstrom R: Surgical anatomy of human parathyroid glands. Surgery 95:14, 1984. 50. Gilmour JR: The gross anatomy of the parathyroid glands. J Pathol 46:133, 1938. 51. Carling T: Molecular pathology of parathyroid tumors. Trends Endocrinol Metab 12:53, 2001. 52. Awad SS, Miskulin J, Thompson N: Parathyroid adenomas versus fourgland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy. World J Surg 27:486, 2003. 53. Skogseid B: Multiple endocrine neoplasia type 1. Br J Surg 90:383, 2003. 54. Arnold A, Shattuck TM, Mallya SM, et al: Molecular pathogenesis of primary hyperparathyroidism. J Bone Miner Res 17:N30, 2002. 55. Talpos GB, Bone HG 3rd, Kleerekoper M, et al: Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: Patient description and effects on the SF-36 health survey. Surgery 128:1013, 2000. 56. Sheldon DG, Lee FT, Neil NJ, et al: Surgical treatment of hyperparathyroidism improves health-related quality of life. Arch Surg 137:1022, 2002. 57. Pasieka JL, Parsons LL, Demeure MJ, et al: Patient-based surgical outcome tool demonstrating alleviation of symptoms following parathyroidectomy in patients with primary hyperparathyroidism. World J Surg 26:942, 2002. 58. Nappi S, Saha H, Virtanen V, et al: Left ventricular structure and

59.

60.

61. 62. 63.

64.

65.

66. 67. 68.

69.

70. 71. 72. 73.

74.

75. 76. 77.

78.

79.

80. 81.

82. 83. 84.

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function in primary hyperparathyroidism before and after parathyroidectomy. Cardiology 93:229, 2000. Vestergaard P, Mollerup CL, Frokjaer VG, et al: Cardiovascular events before and after surgery for primary hyperparathyroidism. World J Surg 27:216, 2003. Wermers RA, Khosla S, Atkinson EJ, et al: Survival after the diagnosis of hyperparathyroidism: A population-based study. Am J Med 104:115, 1998. Deftos LJ: Hypercalcemia in malignant and inflammatory diseases. Endocrinol Metab Clin North Am 31:141, 2002. Scholz DA, Purnell DC: Asymptomatic primary hyperparathyroidism: 10-Year prospective study. Mayo Clin Proc 56:473, 1981. Silverberg SJ, Shane E, Jacobs TP, et al: A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 341:1249, 1999. Anonymous: Proceedings of the NIH Consensus Development Conference on diagnosis and management of asymptomatic primary hyperparathyroidism. Bethesda, Maryland, October 29–31, 1990. J Bone Miner Res 6:S1, 1991. Bilezikian JP, Potts JT Jr., El-Hajj Fuleihan G, et al: Summary statement from a workshop on asymptomatic primary hyperparathyroidism: A perspective for the 21st century. J Clin Endocrinol Metab 87:5353, 2002. Hedback G, Oden A: Increased risk of death from primary hyperparathyroidism—An update. Eur J Clin Invest 28:271, 1998. Sosa JA, Udelsman R: Minimally invasive parathyroidectomy. Surg Oncol 12:125, 2003. Fujii H, Kubo A: Sestamibi scintigraphy for the application of minimally invasive surgery of hyperfunctioning parathyroid lesions. Biomed Pharmacother 56:7s, 2002. Banzo I, Pena FJ, Allende RH, et al: MIBI SPECT and radioguided surgery in the accurate location of a posterior mediastinal parathyroid adenoma. Clin Nucl Med 28:584, 2003. Proctor MD, Sofferman RA: Intraoperative parathyroid hormone testing: What have we learned? Laryngoscope 113:706, 2003. Udelsman R, Donovan PI, Sokoll LJ: One hundred consecutive minimally invasive parathyroid explorations. Ann Surg 232:331, 2000. Perrier ND, Ituarte PH, Morita E, et al: Parathyroid surgery: Separating promise from reality. J Clin Endocrinol Metab 87:1024, 2002. Perrier ND, Ituarte P, Kikuchi S, et al: Intraoperative parathyroid aspiration and parathyroid hormone assay as an alternative to frozen section for tissue identification. World J Surg 24:1319, 2000. Lentsch EJ, Withrow KP, Ackermann D, et al: Parathyromatosis and recurrent hyperparathyroidism. Arch Otolaryngol Head Neck Surg 129:894, 2003. Wells SA Jr., Debenedetti MK, Doherty GM: Recurrent or persistent hyperparathyroidism. J Bone Miner Res 17:N158, 2002. Ziegler R: Hypercalcemic crisis. J Am Soc Nephrol 12:S3, 2001. Llach F, Velasquez Forero F: Secondary hyperparathyroidism in chronic renal failure: Pathogenic and clinical aspects. Am J Kidney Dis 38:S20, 2001. Chou FF, Lee CH, Shu K, et al: Improvement of sexual function in male patients after parathyroidectomy for secondary hyperparathyroidism. J Am Coll Surg 193:486, 2001. Nichol PF, Starling JR, Mack E, et al: Long-term follow-up of patients with tertiary hyperparathyroidism treated by resection of a single or double adenoma. Ann Surg 235:673, 2002. Marx SJ: Hyperparathyroid and hypoparathyroid disorders. N Engl J Med 343:1863, 2000. Auchus RJ: Aldo is back: Recent advances and unresolved controversies in hyperaldosteronism. Curr Opin Nephrol Hypertens 12:153, 2003. Jackson RV, Lafferty A, Torpy DJ, et al: New genetic insights in familial hyperaldosteronism. Ann N Y Acad Sci 970:77, 2002. Stewart PM: Mineralocorticoid hypertension. Lancet 353:1341, 1999. Espiner EA, Ross DG, Yandle TG, et al: Predicting surgically remedial primary aldosteronism: Role of adrenal scanning, posture testing, and adrenal vein sampling. J Clin Endocrinol Metab 88:3637, 2003.

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85. Raff H, Findling JW: A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med 138:980, 2003. 86. Putignano P, Toja P, Dubini A, et al: Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J Clin Endocrinol Metab 88:4153, 2003. 87. Ng L, Libertino JM: Adrenocortical carcinoma: Diagnosis, evaluation and treatment. J Urol 169:5, 2003. 88. Copeland PM: The incidentally discovered adrenal mass. Ann Intern Med 98:940, 1983. 89. Baudin E, Pellegriti G, Bonnay M, et al: Impact of monitoring plasma 1,1-dichlorodiphenildichloroethane (op’-DDD) levels on the treatment of patients with adrenocortical carcinoma. Cancer 92:1385, 2001. 90. Gmyrek GA, New MI, Sosa RE, et al: Bilateral laparoscopic adrenalectomy as a treatment for classic congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency. Pediatrics 109:E28, 2002. 91. Pederson LC, Lee JE: Pheochromocytoma. Curr Treat Options Oncol 4:329, 2003. 92. Lenders JW, Pacak K, Walther MM, et al: Biochemical diagnosis of pheochromocytoma: Which test is best? JAMA 287:1427, 2002.

93. Sackett WR, Bambach CP: Bilateral subtotal laparoscopic adrenalectomy for phaeochromocytoma. Aust N Z J Surg 73:664, 2003. 94. Kanauchi H, Wada N, Clark OH, et al: Apoptosis regulating genes, bcl-2 and bax, and human telomerase reverse transcriptase messenger RNA expression in adrenal tumors: Possible diagnostic and prognostic importance. Surgery 132:1021, 2002. 95. Brunt LM, Moley JF: Adrenal incidentaloma. World J Surg 25:905, 2001. 96. Reincke M: Subclinical Cushing’s syndrome. Endocrinol Metab Clin North Am 29:43, 2000. 97. Libe R, Dall’Asta C, Barbetta L, et al: Long-term follow-up study of patients with adrenal incidentalomas. Eur J Endocrinol 147:489, 2002. 98. Arlt W, Allolio B: Adrenal insufficiency. Lancet 361:1881, 2003. 99. Kebebew E, Siperstein AE, Clark OH, et al: Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg 137:948, 2002. 100. Kelly PA, Samandouras G, Grossman AB, et al: Neurosurgical treatment of Nelson’s syndrome. J Clin Endocrinol Metab 87:5465, 2002.

CHAPTER

38

Pediatric Surgery David J. Hackam, Kurt Newman, and Henri R. Ford

Introduction General Considerations Fluid and Electrolyte Balance Acid-Base Equilibrium Blood Volume and Blood Replacement Hyperalimentation and Nutrition Venous Access Thermoregulation Pain Control Neck Masses Lymphadenopathy Thyroglossal Duct Remnants Pathology and Clinical Manifestations Treatment Branchial Cleft Anomalies Treatment Cystic Hygroma Etiology and Pathology Treatment Torticollis Respiratory System Congenital Diaphragmatic Hernia Pathology Treatment Congenital Lobar Emphysema Congenital Cystic Adenomatoid Malformation Pulmonary Sequestration Bronchogenic Cyst Bronchiectasis Foreign Bodies Airway Ingestion Esophagus Ingestion Esophagus Esophageal Atresia and Tracheoesophageal Fistula Anatomic Varieties Etiology and Pathologic Presentation Clinical Presentation Initial Management Management in the Preterm Infant Primary Surgical Correction Postoperative Course Complications of Surgery Special Circumstances Outcome Corrosive Injury of the Esophagus Gastroesophageal Reflux

Clinical Manifestations Treatment Gastrointestinal Tract Hypertrophic Pyloric Stenosis Clinical Manifestations Treatment Intestinal and Rectal Disorders in the Newborn Duodenal Obstruction Intestinal Atresia Malrotation and Midgut Volvulus Meconium Ileus Necrotizing Enterocolitis Intussusception Appendicitis Intestinal Duplications Meckel’s Diverticulum Mesenteric Cysts Hirschsprung’s Disease Anorectal Malformations Jaundice Approach to the Jaundiced Infant Biliary Atresia Pathogenesis Clinical Presentation Diagnosis Treatment Choledochal Cyst Classification Clinical Presentation Diagnosis Treatment Deformities of the Abdominal Wall Embryology Umbilical Hernia Patent Urachus Omphalocele Clinical Presentation Treatment Gastroschisis Clinical Presentation Treatment Prune-Belly Syndrome Clinical Presentation Treatment Inguinal Hernia Embryology Clinical Manifestations Surgical Repair

1471

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Genitalia Undescended Testis Embryology Clinical Presentation Treatment Vaginal Anomalies Ovarian Cysts and Tumors Pathologic Classification Clinical Presentation Surgical Management Ovarian Cysts in the Newborn Ambiguous Genitalia Embryology True Hermaphroditism Male Pseudohermaphroditism Female Pseudohermaphroditism Mixed Gonadal Dysgenesis Management

surgical patient with a mix of fear and anxiety. Nonetheless, they generally complete their pediatric surgical experience with a clear sense of the enormous ability of children to tolerate large operations, and with a true appreciation for the precision required in their care, both in the operating room and during the perioperative period. The specialty has evolved considerably in its ability to care for the smallest of patients with surgical disorders, so that in utero surgery is now an option in certain circumstances. Similarly, our understanding of the pathophysiology of the diseases that pediatric surgeons face has increased greatly to the point where our focus has shifted from an understanding of anatomy and physiology to an appreciation of the molecular or cellular pathways that regulate tissue growth and differentiation. There are few specialties in all of medicine that provide the opportunity to intervene in such a positive manner in such a wide array of diseases, and to receive the most heartfelt appreciation possible—that of a parent whose child’s life has forever been improved.

Pediatric Malignancy

GENERAL CONSIDERATIONS

Wilms’ Tumor Clinical Presentation Genetics Surgical Treatment Chemotherapy Neuroblastoma Clinical Presentation Diagnostic Evaluation Prognostic Indicators Surgery Neuroblastoma in Infants Rhabdomyosarcoma Prognosis Teratoma Sacrococcygeal Teratoma Liver Tumors Surgery

Fluid and Electrolyte Balance

Trauma in Children Mechanisms of Injury Initial Management Evaluation of Injury Injuries to the Central Nervous System Thoracic Injuries Abdominal Injuries Fetal Intervention Surgery for Lower Urinary Tract Obstruction Fetal Surgery for Congenital Diaphragmatic Hernia Fetal Surgery for Myelomeningocele The Ex-Utero Intrapartum Treatment Procedure

INTRODUCTION In his 1953 classic textbook titled The Surgery of Infancy and Childhood, Dr. Robert E. Gross summarized the essential challenge of pediatric surgery: “Those who daily operate upon adults, even with the greatest of skill, are sometimes appalled—or certainly are not at their best—when called upon to operate upon and care for a tiny patient. Something more than diminutive instruments or scaled-down operative manipulations are necessary to do the job in a suitable manner.” To this day, surgical residents often approach the pediatric

In managing the pediatric surgical patient, an understanding of fluid and electrolyte balance is critical, as the margin between dehydration and fluid overload is small. Several surgical diagnoses, such as gastroschisis or short-gut syndrome, are characterized by a predisposition to fluid loss. Others require judicious restoration of intravascular volume in order to prevent cardiac failure, as in patients with congenital diaphragmatic hernia and associated pulmonary hypertension. It is important to realize that the infant’s physiologic day is approximately 8 hours in duration. A careful assessment of the individual patient’s fluid balance tally—showing fluid intake and output fluid for the previous 8 hours—will prevent dehydration or fluid overload. Clinical signs of dehydration include tachycardia and reduced urine output as well as a depressed fontanelle, lethargy, and poor feeding. Fluid overload is often manifested by the onset of new oxygen requirements, respiratory distress, tachypnea, and tachycardia. The infant is born with a surplus of body water, which is normally excreted by the end of the first week of life. At birth, fluid requirements are 65 mL/kg (750 mL/m2 ) and increase to 100 mL/kg (1000 mL/m2 ) by the end of the first week. Daily maintenance fluids for most children can be estimated using the formula: 100 mL/kg for the first 10 kg plus 50 mL/kg for 11 to 20 kg plus 25 mL/kg for each additional kilogram of body weight thereafter. Because intravenous fluid orders are written as milliliters per hour, this can be conveniently converted to 4 mL/kg per hour up to 10 kg by adding 2 mL/kg per hour for 11 to 20 kg, and 1 mL/kg per hour for each additional kilogram of body weight thereafter. For example, a 26-kg child has an estimated maintenance fluid requirement of (10 × 4)+(10 × 2) + (6 × 1) = 66 mL/h in the absence of massive fluid losses or shock. Fluid for maintenance is generally provided as 5% dextrose in one quarter normal saline. For short-term intravenous therapy, the administration of 5 mEq/kg per day of sodium and 2 mEq/kg per day of potassium will satisfy the daily need. Fluid and electrolyte losses secondary to protracted vomiting or diarrhea are corrected by modifying this formula according to the measured losses. In infants the normal serum osmolarity is between 280 and 290 mmol/L. Newborns have the ability to concentrate their urine well by the fifth day of life; thus urine concentration as well as output must be considered when ordering intravenous fluids postoperatively. If the child has a significant ongoing fluid loss

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(e.g., from a nasogastric tube), it is best to properly replace that loss with IV fluids at least every 4 hours. A typical replacement formula is D5 1/2 normal saline +20 mEq KCl/L. Whatever the formula used to calculate fluid replacement for the infant or small child, the optimal strategy is to analyze serum electrolytes and fluid losses and to replace the appropriate constituents precisely.

Acid-Base Equilibrium Acute metabolic acidosis usually implies inadequate tissue perfusion, and is a serious disorder in children. Potentially life-threatening causes that are specific for the pediatric population must be sought, including intestinal ischemia from necrotizing enterocolitis (in the neonate), midgut volvulus, or incarcerated hernia. Other causes include chronic bicarbonate loss from the gastrointestinal tract or an acid accumulation as in chronic renal failure. Respiratory acidosis implies hypoventilation, the cause of which should be apparent. Treatment of acute metabolic acidosis should be aimed at restoring tissue perfusion by addressing the underlying abnormality first. For severe metabolic acidemia where the serum pH is less than 7.25, sodium bicarbonate should be administered using the following guideline: base deficit × weight in kilograms × 0.5 (in newborns). The last factor in the equation should be 0.4 for smaller children, and 0.3 for older children. The dose should be diluted to a concentration of 0.5 mEq/mL because full-strength sodium bicarbonate is hyperosmolar. One half the corrective dose is given, and the serum pH is measured again. During cardiopulmonary resuscitation (CPR), one half the corrective dose can be given as an intravenous bolus and the other half given slowly intravenously. Respiratory alkalosis is usually caused by hyperventilation, which is readily correctable. Metabolic alkalosis most commonly implies gastric acid loss, as in the child with pyloric stenosis or overaggressive diuretic therapy. In the child with gastric fluid loss, IV fluids of 5% dextrose, 0.5% normal saline, and 20 mEq KCl/L usually correct the alkalosis.

Blood Volume and Blood Replacement Criteria for blood transfusion in infants and children remain poorly defined. The decision to transfuse a critically-ill pediatric patient may depend on a number of clinical features that include the patient’s age, primary diagnosis, the presence of ongoing bleeding, coagulopathy, hypoxia, hemodynamic compromise, lactic acidosis, and cyanotic heart disease, as well as overall severity of illness. A recent survey of transfusion practices among pediatric intensivists showed that the baseline hemoglobin levels that would prompt them to recommend a red blood cell (RBC) transfusion ranged from 7 to 13 g/dL. Patients with cyanotic heart disease are often transfused to higher hemoglobin values, although the threshold for transfusion in this population remains to be defined. To decrease the need for transfusion, other strategies have been considered. Studies in both critically-ill adults and neonates have shown that administration of erythropoietin decreases RBC transfusion requirements. In general terms, there is a trend toward an avoidance of the use of RBC products whenever possible, as current studies suggest that lower hemoglobin concentrations are well tolerated by many groups of patients, and that administration of RBCs may have unintended negative consequences. A useful guideline for estimation of blood volume for the infant is 85 mL/kg of body weight. When packed red blood cells (PRBC) are utilized, the transfusion requirement is calculated as 10 mL/kg, which roughly is equivalent to a 500-mL transfusion for a 70-kg

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adult. At the authors’ institution, the following formula is used to determine the volume of blood in mL: (target hematocrit − current hematocrit) × weight (kg) × 80/65 = blood volume In the child, coagulation deficiencies may rapidly assume clinical significance after extensive blood transfusion. It is advisable to have fresh frozen plasma and platelets available if more than 30 mL/kg have been transfused. Plasma is given in a dose of 10 to 20 mL/kg, and platelets are given in a dose of 1 unit/5 kg. Each unit of platelets consists of 40 to 60 mL of fluid, and platelets can be spun down to a platelet “button” for infants who require restricted fluid administration. Following transfusion of PRBC to neonates, with tenuous fluid balance, a single dose of a diuretic (such as furosemide 1 mg/kg) may help to facilitate excretion of the extra fluid load.

Hyperalimentation and Nutrition The nutritional requirements of the surgical neonate must be met in order for the child to grow and to heal surgical wounds. If inadequate protein and carbohydrate calories are given, the child may not only fail to recover from surgery, but may also exhibit growth failure and impaired development of the central nervous system. Neonates that are particularly predisposed to protein-calorie malnutrition include those with gastroschisis, intestinal atresia, or intestinal insufficiency from other causes such as necrotizing enterocolitis. The protein and caloric requirements for the surgical neonate are shown in Table 38-1. Nutrition can be provided via either the enteral or parenteral routes. Whenever possible, the enteral route is preferred, because it not only promotes the growth and function of the gastrointestinal system, but also ensures that the infant learns how to feed. There are various enteral feeding preparations available, which are outlined in Table 38-2. The choice of formula is based upon the clinical state of the individual child. Pediatric surgeons are occasionally faced with situations in which oral feeding is not possible. This problem can be seen in the extremely premature infant who has not yet developed the feeding skills, or in the infant with concomitant craniofacial abnormalities that impair sucking. In these instances, enteral feeds can be administered using either a nasojejunal or a gastrostomy tube. When the gastrointestinal tract cannot be used because of mechanical, ischemic, inflammatory, or functional disorders, parenteral alimentation must be given. When an extended period of parenteral nutrition is required, central venous catheters are placed. Peripheral intravenous alimentation can be given, utilizing less concentrated but greater volumes of solutions. To prevent the development of trace metal deficiencies, supplemental copper, zinc, and iron are provided to patients receiving long-term total parenteral nutritional (TPN) support. Table 38-1 Nutritional Requirements for the Pediatric Surgical Patient Age 0 to 6 months 6 months–1 year 1 year–3 years 4 years–6 years 7 years–10 years 11 years–14 years 15 years–18 years

Calories (kcal/kg per day)

Protein (g/kg per day)

100–120 100 100 90 70 55 45

2 1.5 1.2 1 1 1 1

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Table 38-2 Formulas for Pediatric Surgical Neonates Formula

kcal/mL

Protein (g/mL)

Fat (g/mL)

Carbohydrate (g/mL)

0.67

0.011

0.04

0.07

0.67 0.67

0.015 0.015

0.038 0.036

0.069 0.072

0.67 0.67

0.02 0.018

0.036 0.037

0.07 0.068

0.67 0.67

0.019 0.019

0.028 0.038

0.091 0.068

0.80

0.024

0.041

0.089

Human Milk Milk Based Enfamil 20 Similac 20 Soy Based Prosobee Isomil Special Pregestimil Alimentum Preterm Enfamil Premature

A major complication of long-term TPN is the development of liver failure. This is characterized by cholestatic liver disease that eventually progresses to end-stage hepatic fibrosis. To prevent this major complication, concomitant enteral feedings must be instituted, and the gastrointestinal tract should be used as soon as possible. In instances in which proximal stomas are in place, continuity of the gastrointestinal tract should be restored as soon as possible. Where intestinal insufficiency is associated with dilation of the small intestine, tapering or intestinal lengthening procedures may be beneficial. Other strategies to minimize the development of TPNrelated liver disease include avoidance of infection by meticulous catheter care, aggressive treatment of any infection, and early cycling of parenteral nutrition to include a period during the day when parenteral nutrition is not given.

Venous Access Obtaining reliable vascular access in an infant or child is a major responsibility of the pediatric surgeon. The goal should always be to place the catheter in the least invasive, least risky, and least painful manner, and in a location that is most accessible and facilitates use of the catheter without complications for as long as needed. In infants, the general approach of these authors is to place a central venous catheter using a cutdown approach, either in the antecubital fossa, external jugular vein, facial vein, or proximal saphenous vein. If the internal jugular vein is used, placing a purse-string suture at the venotomy is recommended, if possible, to prevent venous occlusion. In infants over 2 kg and in older children, percutaneous access of the subclavian, internal jugular, or femoral veins is possible in most cases, and central access is achieved using the Seldinger technique. The catheters are tunneled to an exit site separate from the venotomy site. Regardless of whether the catheter is placed by a cutdown approach or percutaneously, a chest x-ray to confirm central location of the catheter tip and to exclude the presence of a pneumothorax or hemothorax is mandatory. When discussing the placement of central venous catheters with parents, it is important to note that the complication rate for central venous lines in children is high. The incidence of catheter-related sepsis or infection approaches 10% in many series. Superior or inferior vena caval occlusion is a significant risk, particularly in the smallest premature patients.

temperature. Because they are unable to shiver and lack stores of fat, their potential for thermogenesis is impaired. This is compounded by the administration of anesthetic and paralyzing agents. Since these patients lack adaptive mechanisms to cope with the environment, the environment must be regulated. Attention to heat conservation during transport of the infant to and from the operating room is essential. Transport units incorporating heating units are necessary for premature infants. In the operating room, the infant is kept warm by the use of overhead heating lamps, a heating blanket, warming of inspired gases, and coverage of the extremities and head with occlusive materials. During abdominal surgery, extreme care is taken to avoid wet and cold drapes. All fluids used to irrigate the chest or abdomen must be warmed to body temperature. Constant monitoring of the child’s temperature is critical in a lengthy procedure, and the surgeon should continuously communicate with the anesthesiologist regarding the temperature of the patient. The development of hypothermia in infants and children can result in cardiac arrhythmias or coagulopathy. These potentially life-threatening complications can be avoided by careful attention to thermoregulation.

Pain Control Despite previously held beliefs to the contrary, it has now been definitively established that neonates experience pain. Therefore, any procedure that is performed on a neonate must be accompanied by the provision of adequate analgesia. There is a range of pain management options that can improve the child’s well being, as well as the parents’ sense of comfort. The use of a pacifier, which may be dipped in sucrose, has been shown to decrease crying time and neonatal pain scores after minor procedures. For situations in which more pain is expected, intravenous narcotic agents should be used. Morphine and fentanyl have an acceptable safety margin and can be administered judiciously to neonates and children. A recent randomized trial of neonates on ventilators showed that the use of a morphine infusion decreased the incidence of intraventricular hemorrhage by 50%. Additional analgesic modalities include the use of topical anesthetic ointment (e.g., EMLA [eutectic mixture of local anesthetics] cream), and the use of regional anesthesia, such as caudal blocks for hernias, or epidural infusion for thoracic surgery. In the postoperative period, patient-controlled analgesia (PCA) is another excellent method of pain control. By ensuring that the pediatric surgical patient has adequate analgesia, the surgeon ensures that the patient receives the most humane and thorough treatment, and provides important reassurance to all other members of the health care team and to the family that pain control is a high priority.

NECK MASSES The management of neck masses in children is determined by their location and the length of time that they have been present. Neck lesions are found either in the midline or lateral compartments. Midline masses include thyroglossal duct remnants, thyroid masses, thymic cysts, or dermoid cysts. Lateral lesions include branchial cleft remnants, cystic hygromas, vascular malformations, salivary gland tumors, torticollis, and lipoblastoma (a rare benign mesenchymal tumor of embryonal fat occurring in infants and young children). Enlarged lymph nodes and rare malignancies such as rhabdomyosarcoma can occur either in the midline or laterally.

Thermoregulation Careful regulation of the ambient environment of infants and children is crucial, as these patients are extremely thermolabile. Premature infants are particularly susceptible to changes in environmental

Lymphadenopathy The most common cause of a neck mass in a child is an enlarged lymph node, which typically can be found laterally or in the midline.

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The patient is usually referred to the pediatric surgeon for evaluation after the mass has been present for several weeks. A detailed history and physical examination often helps determine the likely etiology of the lymph node, and the need for excisional biopsy. Enlarged tender lymph nodes are usually the result of a bacterial infection (Staphylococcus or Streptococcus). Treatment of the primary cause (e.g., otitis media or pharyngitis) with antibiotics often is all that is necessary. However, when the involved nodes become fluctuant, incision and drainage are indicated. More chronic forms of lymphadenitis, including infections with tuberculosis, atypical mycobacteria, as well as cat-scratch fever, are determined based on serologic findings and excisional biopsy. The lymphadenopathy associated with infectious mononucleosis can be diagnosed based on serology. When the neck nodes are firm and fixed, and others also are present in the axillae or groin, or the history suggests the presence of a hematologic malignancy, excisional biopsy is indicated. In these cases, a chest radiograph must be obtained to evaluate whether a mediastinal mass also is present. The presence of a large mediastinal mass should be identified preoperatively, as this may cause airway compression when muscle relaxants are administered. Under these cirumstances, tissue should be obtained under local anesthesia. The tissue is sent to pathology fresh for evaluation.

recurrence is more frequent following infection. According to a recent review, factors predictive of recurrence included more than two infections prior to surgery, age under 2 years, and inadequate initial operation.

Thyroglossal Duct Remnants

Treatment

Pathology and Clinical Manifestations

The treatment is surgical, and complete removal of the cyst and tract is necessary for cure. Dissection of the sinus tract is facilitated by passing a fine lacrimal duct probe through the external opening into the tract and utilizing it as a guide for dissection. Injection of a small amount of methylene blue dye into the tract also may be useful. A series of two or sometimes three small transverse incisions in a “stepladder” fashion is preferred to a long oblique incision in the neck, which is cosmetically undesirable. Branchial cleft cysts can present as abscesses. In these cases, initial treatment includes incision and drainage with a course of antibiotics to cover Staphylococcus and Streptococcus species, followed by excision of the cyst after the infection resolves.

The thyroid gland buds off the foregut diverticulum at the base of the tongue in the region of the future foramen cecum at 3 weeks of embryonic life. As the fetal neck develops, the thyroid tissue becomes more anterior and caudad until it rests in its normal position. The “descent” of the thyroid is intimately connected with the development of the hyoid bone. Residual thyroid tissue left behind in the migration may persist and subsequently present in the midline of the neck as a thyroglossal duct cyst. The mass is most commonly appreciated in the 2- to 4-year-old child when the baby fat disappears and irregularities in the neck become more readily apparent. Usually the cyst is encountered in the midline at or below the level of the hyoid bone, and moves up and down with swallowing or with protrusion of the tongue. Occasionally it presents as an intrathyroidal mass. Most thyroglossal duct cysts are asymptomatic. If the duct retains its connection with the pharynx, infection may occur, and the resulting abscess will necessitate incision and drainage, occasionally resulting in a salivary fistula. Submental lymphadenopathy and midline dermoid cysts can be confused with a thyroglossal duct cyst. Rarely, midline ectopic thyroid tissue masquerades as a thyroglossal duct cyst, and may represent the patient’s only thyroid tissue. Therefore, if there is any question regarding the diagnosis or if the thyroid gland cannot be palpated in its normal anatomic position, it is advisable to obtain a nuclear scan to confirm the presence of a normal thyroid gland. Although rarely the case in children, in adults the thyroglossal duct may contain thyroid tissue that can undergo malignant degeneration. The presence of malignancy in a thyroglossal cyst should be suspected when the cyst grows rapidly, or when the ultrasound demonstrates a complex anechoic pattern or the presence of calcification.

Treatment If the cyst presents with an abscess, treatment should consist of drainage and antibiotics. Following resolution of the inflammation, resection of the cyst in continuity with the central portion of the hyoid bone and the tract connecting to the pharynx, in addition to ligation at the foramen cecum (the Sistrunk operation) is curative. Lesser operations result in unacceptably high recurrence rates, and

Branchial Cleft Anomalies Paired branchial clefts and arches develop early in the fourth gestational week. The first cleft and the first, second, third, and fourth pouches give rise to adult organs. The embryologic communication between the pharynx and the external surface may persist as a fistula. A fistula is seen most commonly with the second branchial cleft, which normally disappears, and extends from the anterior border of the sternocleidomastoid muscle superiorly, inward through the bifurcation of the carotid artery, and enters the posterolateral pharynx just below the tonsillar fossa. The branchial cleft remnants may contain small pieces of cartilage and cysts, but internal fistulas are rare. A second branchial cleft sinus is suspected when clear fluid is noted draining from the external opening of the tract at the anterior border of the lower third of the sternocleidomastoid muscle. Rarely, branchial cleft anomalies occur in association with biliary atresia and congenital cardiac anomalies, an association that is referred to as Goldenhar’s complex.

Cystic Hygroma Etiology and Pathology Cystic hygroma (lymphangioma) occurs as a result of sequestration or obstruction of developing lymph vessels in approximately 1 in 12,000 births. Although the lesion can occur anywhere, the most common sites are in the posterior triangle of the neck, axilla, groin, and mediastinum. The cysts are lined by endothelium and filled with lymph. Occasionally unilocular cysts occur, but more often there are multiple cysts infiltrating the surrounding structures and distorting the local anatomy. A particularly troublesome variant of cystic hygroma is that which involves the tongue, floor of the mouth, and structures deep in the neck. Adjacent connective tissue may show extensive lymphocytic infiltration. The mass may be apparent at birth or may appear and enlarge rapidly in the early weeks or months of life as lymph accumulates; most present by age 2 years (Fig. 38-1A). Extension of the lesion into the axilla or mediastinum occurs about 10% of the time and can be demonstrated preoperatively by chest x-ray, ultrasound (US), or computed tomographic (CT) scan. Cystic hygromas occasionally contain nests of vascular tissue. These poorly supported vessels may bleed and produce rapid enlargement and discoloration of the hygroma. Infection within the cysts, usually caused by Streptococcus or Staphylococcus, may occur. In the neck this can cause rapid enlargement, which may result in airway compromise. Rarely, it may be necessary to carry out percutaneous aspiration of a cyst to relieve respiratory distress.

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A

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B

FIG. 38-1. A . Left cervical cystic hygroma in a 2-day-old baby. B . Intraoperative photograph showing a vessel loop around the spinal accessory nerve.

The diagnosis of cystic hygroma by prenatal US before 30 weeks’ gestation has detected a “hidden mortality,” as well as a high incidence of associated anomalies, including abnormal karyotypes and hydrops fetalis. Occasionally, very large lesions can cause obstruction of the fetal airway. Such obstruction can result in the development of polyhydramnios by impairing the ability of the fetus to swallow amniotic fluid. In these circumstances, the airway is usually markedly distorted, which can result in immediate airway obstruction unless the airway is secured at the time of delivery. Orotracheal intubation or urgent emergency tracheostomy while the infant remains attached to the placenta, the ex utero intrapartum technique (EXIT) procedure, may be necessary to secure the airway.

Treatment Surgical excision is the treatment of choice for cystic hygromas. Total removal may not be possible because of the extent of the hygroma and its proximity to, and intimate relationship with, adjacent nerves, muscles, and blood vessels (see Fig. 38-1B). Radical ablative surgery is not indicated for this lesion. Conservative excision and unroofing of remaining cysts is advised, with repeated partial excision of residual hygroma if necessary, preserving all adjacent crucial structures. Postoperative wound drainage is important and is best accomplished by closed-suction technique. Fluid may accumulate beneath the surgically-created flaps in the area from which the hygroma was excised, requiring multiple needle aspirations. Injection of sclerosing agents (OK-432 or bleomycin) with favorable results has been reported. OK-432 is composed of a lyophilized mixture of group A Streptococcus pyogenes, and has been used in neonates without systemic toxicity. The use of these agents has not been widely adopted.

Torticollis The presence of a lateral neck mass in infancy in association with rotation of the head toward the opposite side of the mass indicates the presence of congenital torticollis. This lesion results from fibrosis of the sternocleidomastoid muscle. The mass may be palpated in the affected muscle in approximately two-thirds of cases. Histologically, the lesion is characterized by the deposition of collagen

and fibroblasts around atrophied muscle cells. In the majority of cases, physical therapy is of benefit. Rarely surgical transection of the affected muscle can be curative, if needed.

RESPIRATORY SYSTEM Congenital Diaphragmatic Hernia Pathology During formation of the diaphragm, the pleural and coelomic cavities remain in continuity by means of the pleuroperitoneal canal. The posterolateral communication is the last to be closed by the developing diaphragm. Failure of diaphragmatic development leaves a posterolateral defect known as a Bochdalek hernia. This anomaly is encountered more commonly on the left (80 to 90%). Incomplete development of the posterior diaphragm allows the abdominal viscera to fill the chest cavity. The abdominal cavity is small and underdeveloped and remains scaphoid after birth. Both lungs are hypoplastic, with decreased bronchial and pulmonary artery branching. Lung weight, lung volume, and deoxyribonucleic acid (DNA) content also are decreased, but these findings are more striking on the ipsilateral side. In many instances, evidence suggests that a paucity of surfactant is present, which compounds the degree of respiratory insufficiency. Amniocentesis with karyotyping may show chromosomal defects, especially trisomy 18 and 21. Associated anomalies, once thought to be uncommon, are identified in 40% of these infants, and most commonly involve the heart, brain, genitourinary system, craniofacial structures, or limbs. Prenatal ultrasonography is successful in making the diagnosis of congenital diaphragmatic hernia (CDH) as early as 15 weeks’ gestation. Ultrasound findings include herniated abdominal viscera, abnormal anatomy of the upper abdomen, and mediastinal shift away from the herniated viscera (Fig. 38-2). Accurate prenatal prediction of outcome for fetuses who have CDH is difficult. A useful index of severity for patients with left CDH is the lung-to-head ratio (LHR), which is the product of the length and the width of the right lung at the level of the cardiac atria divided by the head circumference (all measurements in millimeters). An LHR value of less than 1.0 is

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FIG. 38-2. Prenatal ultrasound of a fetus with a congenital diaphragmatic hernia. Arrows point to the location of the diaphragm. Arrowhead points to the stomach, which is in the thoracic cavity.

associated with a poor prognosis, whereas an LHR greater than 1.4 predicts a more favorable outcome. Following delivery, the diagnosis of CDH is made by chest x-ray (CXR) (Fig. 38-3). The differential diagnosis includes congenital cystic adenomatoid malformation, in which the intrathoracic loops of bowel may be confused with multiple lung cysts. The vast majority of infants with CDH develop immediate respiratory distress, which is due to the combined effects of three factors. First, the air-filled bowel in the chest compresses the mobile mediastinum, which shifts to the opposite side of the chest, compromising air exchange in the contralateral lung. Second, pulmonary hypertension develops. This phenomenon results in persistent fetal circulation, with resultant decreased pulmonary perfusion and impaired gas exchange. Finally, the lung on the affected side is often markedly hypoplastic, such that it is essentially nonfunctional. Varying degrees of pulmonary hypoplasia on the opposite side may compound these effects. As a result, neonates with CDH are extremely sick, and the overall mortality in most series is approximately 60 to 70%.

Treatment Many infants are symptomatic at birth due to hypoxia, hypercarbia, and metabolic acidosis. Prompt cardiorespiratory stabilization is mandatory. It is interesting that the first 24 to 48 hours after birth are often characterized by a period of relative stability, with high Pao2 (partial pressure of arterial oxygen) levels and relatively good perfusion. This has been termed the “honeymoon period,” and is often followed by progressive cardiorespiratory deterioration in the majority of patients. In the past, correction of the hernia was felt to be a surgical emergency, and these patients underwent surgery shortly after birth. It is now accepted that the presence of persistent pulmonary hypertension that results in right-to-left shunting across the open foramen ovale or the ductus arteriosus, and the degree of pulmonary hypoplasia, are the leading causes of cardiorespiratory insufficiency. Therefore, current management is directed toward

preventing or reversing the pulmonary hypertension, and minimizing barotrauma while optimizing oxygen delivery. To achieve this goal, infants are placed on mechanical ventilation using relatively low or “gentle” settings that prevent overinflation of the noninvolved lung. Paco2 (partial arterial pressure of carbon dioxide) levels in the range of 50 to 60 mm Hg or higher are acceptable, as long as the pH remains 7.25 or greater. If these objectives cannot be achieved using conventional ventilation, high-frequency oscillatory ventilation (HFOV) may be employed to avoid the injurious effects of conventional tidal volume ventilation. Echocardiography is used to assess the degree of pulmonary hypertension and to identify the presence of a coexisting cardiac anomaly. To minimize the degree of pulmonary hypertension, inhaled nitric oxide may be used. In certain patients, this agent significantly improves pulmonary perfusion, as manifested by improved oxygenation. Nitric oxide is administered into the ventilation circuit, and is used in concentrations up to 40 parts per million. Correction of acidosis using bicarbonate solution may minimize the degree of pulmonary hypertension. As the degree of pulmonary hypertension becomes hemodynamically significant, right-sided heart failure develops and systemic perfusion is impaired. Administration of excess intravenous fluid will compound the degree of cardiac failure, and lead to marked peripheral edema. Inotropic support using epinephrine is therefore useful in optimizing cardiac contractility and maintaining mean arterial pressure. Infants with CDH who remain severely hypoxic despite maximal ventilatory care may be candidates for treatment of their respiratory failure by extracorporeal membrane oxygenation (ECMO). Venovenous or venoarterial bypass is used. Venovenous bypass is established with a single cannula through the internal jugular vein, with blood removed from and infused into the right atrium by separate ports. Venoarterial bypass is used preferentially by some centers because it provides the cardiac support that is often needed. The right atrium is cannulated by means of the internal jugular vein and the aortic arch through the right common carotid artery. As much

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FIG. 38-3. Chest x-ray showing a left congenital diaphragmatic hernia.

of the cardiac output is shunted through the membrane oxygenator as needed to provide oxygenated blood to the infant and remove carbon dioxide. The infant is maintained on bypass until the pulmonary hypertension is reversed and lung function, as measured by compliance, is improved. This is usually seen within 7 to 10 days, but in some infants it may take up to 3 weeks to occur. The use of ECMO is associated with significant risk and because patients require systemic anticoagulation, bleeding complications are the most significant. They may occur intracranially or at the site of cannula insertion, and can be life threatening. Systemic sepsis is a significant problem, and may necessitate decannulation. Criteria for placing infants on ECMO include the presence of normal cardiac anatomy by echocardiography, the absence of fatal chromosome anomalies, and the expectation that the infant would die without ECMO. Traditionally, a threshold of weight greater than 2.5 kg and gestational age greater than 34 weeks has been used to select patients for ECMO, although success has been achieved at weights as low as 1.8 kg. It is important to emphasize that although ECMO may salvage a population of neonates with refractory pulmonary hypertension, the use of this technique remains controversial. A strategy that does not involve the use of ECMO, but instead emphasizes the use of permissive hypercapnia and the avoidance of barotrauma, may provide equal overall outcome in patients with CDH. This likely reflects the fact that mortality is related to the degree of pulmonary hypoplasia and the presence of congenital anomalies, neither of which are correctable by ECMO. The timing of diaphragm repair is controversial. In patients that are not placed on ECMO, most surgeons perform repair once the

hemodynamic status has been optimized. In neonates that are on bypass, some surgeons perform early repair on bypass; others wait until the infant’s lungs are fully recovered, repair the diaphragm, and discontinue bypass within hours of surgery. Still others repair the diaphragm only after the infant is off bypass. Operative repair of the diaphragmatic hernia is best accomplished by an abdominal approach. Through a subcostal incision, the abdominal viscera are withdrawn from the chest, exposing the defect in the diaphragm. Care must be taken when reducing the spleen and liver, as bleeding from these structures can be fatal. The anterior margin is often apparent, while the posterior muscular rim is attenuated. If the infant is heparinized on bypass, minimal dissection of the muscular margins is performed. Electrocautery is used liberally to minimize postoperative bleeding. Most infants who require ECMO support prior to hernia repair have large defects, often lacking the medial and posterior margins. Prior to the availability of ECMO therapy, most of these infants died. About three fourths of infants repaired on bypass require prosthetic material to patch the defect, suturing it to the diaphragmatic remnant or around ribs or costal cartilages for large defects. If there is adequate muscle for closure, a single layer of nonabsorbable horizontal mattress suture is used to close the defect. Just before the repair is complete, a chest tube may be positioned in the thoracic cavity. We tend to reserve the use of chest tubes for patients who are repaired on ECMO, as these patients are at risk for developing a hemothorax, which can significantly impair ventilation. Anatomic closure of the abdominal wall may be impossible after reduction of the viscera. Occasionally a prosthetic patch of GoreTex or Surgisis may be sutured to the fascia and facilitate closure. The patch can be removed at a later time and the ventral hernia can be closed at that time or subsequently. If the diaphragm has been repaired on ECMO, weaning and decannulation are accomplished as soon as possible. All infants are ventilated postoperatively to maintain preductal arterial oxygenation of 80 to 100 mm Hg. Very slow weaning from the ventilator is necessary to avoid recurrent pulmonary hypertension. Oscillation ventilation may be switched to conventional ventilation as part of the process of weaning.

Congenital Lobar Emphysema Congenital lobar emphysema (CLE) is a condition manifested during the first few months of life as a progressive hyperexpansion of one or more lobes of the lung. It can be life threatening in the newborn period, but in the older infant it causes less respiratory distress. Air entering during inspiration is trapped in the lobe; on expiration, the lobe cannot deflate and progressively overexpands, causing atelectasis of the adjacent lobe or lobes. This hyperexpansion eventually shifts the mediastinum to the opposite side and compromises the other lung. CLE usually occurs in the upper lobes of the lung (left greater than right), followed next in frequency by the right middle lobe, but it also can occur in the lower lobes. It is caused by intrinsic bronchial obstruction from poor bronchial cartilage development or extrinsic compression. Approximately 14% of children with this condition have cardiac defects, with an enlarged left atrium or a major vessel causing compression of the ipsilateral bronchus. Symptoms range from mild respiratory distress to full-fledged respiratory failure, with tachypnea, dyspnea, cough, and late cyanosis. These symptoms may be stable or they may progress rapidly or result in recurrent pneumonia. Occasionally, infants with CLE present with failure to thrive, which likely reflects the increased work associated with the overexpanded lung. Diagnosis is made by chest x-ray, which shows a hyperlucent affected lobe with adjacent

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FIG. 38-5. CT scan of the chest showing a congenital cystic adenomatoid malformation of the left lower lobe.

Pulmonary Sequestration

FIG. 38-4. Congenital lobar emphysema of the left upper lobe in a 2-week-old boy. Mediastinal shift is present.

lobar compression and atelectasis with varying degrees of shift of the mediastinum to the opposite side and compression of the contralateral lung (Fig. 38-4). If definitive diagnosis is unclear by chest x-ray, CT scan may be helpful. Unless foreign body or mucus plugging is suspected as a cause of hyperinflation, bronchoscopy is not advisable because it can produce more air trapping and cause life-threatening respiratory distress in a stable infant. Treatment is resection of the affected lobe. Unless symptoms necessitate earlier surgery, resection can usually be performed after the infant is several months of age. The prognosis is excellent.

Congenital Cystic Adenomatoid Malformation This malformation consists of cystic proliferation of the terminal airway, producing cysts lined by mucus-producing respiratory epithelium, and elastic tissue in the cyst walls without cartilage formation. There may be a single cyst with a wall of connective tissue containing smooth muscle. Cysts may be large and multiple (type I), smaller and more numerous (type II), or they may resemble fetal lung without macroscopic cysts (type III). Most congenital cystic adenomatoid malformation (CCAM) occurs in the left lower lobe. However, this lesion can occur in any lobe and may occur in both lungs simultaneously. In the left lower lobe, type I may be confused at birth with a congenital diaphragmatic hernia. Clinical symptoms may range from none at all to severe respiratory failure at birth. The cyst(s), whether single or multiple, can produce air trapping and may be confused with congenital lobar emphysema pneumatoceles or even pulmonary sequestrations. They also can be involved with repeated infections and produce fever and cough in older infants and children. The diagnosis often can be made by CXR. In certain cases US or CT scan may be definitive (Fig. 38-5). Prenatal US may suggest the diagnosis. In the newborn period, US may also be useful, especially to distinguish between CCAM and congenital diaphragmatic hernia. Resection is curative and may need to be performed urgently in the infant with severe respiratory distress. Lobectomy is usually required (Fig. 38-6). Prognosis is excellent.

Pulmonary sequestration is uncommon and consists of a mass of lung tissue, usually in the left lower chest, occurring without the usual connections to the pulmonary artery or tracheobronchial tree, yet with a systemic blood supply from the aorta. There are two kinds of sequestration. Extralobar sequestration is usually a small area of nonaerated lung separated from the main lung mass, with a systemic blood supply, that is located immediately above the left diaphragm. It is commonly found in cases of congenital diaphragmatic hernia. Intralobar sequestration more commonly occurs within the parenchyma of the left lower lobe, but can occur on the right. There is no major connection to the tracheobronchial tree, but a secondary connection may be established, perhaps through infection or via adjacent intrapulmonary shunts. The blood supply is systemic from the aorta, is often multiple vessels, and frequently originates below the diaphragm (Fig. 38-7). Venous drainage of both types can be systemic or pulmonary. The cause of sequestration is unknown, but most probably involves an abnormal budding of the developing lung that picks up a systemic blood supply and never becomes connected with the bronchus or pulmonary vessels. Extralobar sequestration is asymptomatic and is usually discovered incidentally on CXR. If the

FIG. 38-6. Intraoperative photograph showing the left lower lobe congenital cystic adenomatoid malformation seen in Fig. 38-5.

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location of the lesion. Treatment consists of resection of the cyst, which may need to be undertaken in emergency circumstances for airway or cardiac compression. Resection can be performed either as an open procedure or using a thoracoscopic approach.

Bronchiectasis Bronchiectasis is an abnormal and irreversible dilatation of the bronchi and bronchioles associated with chronic suppurative disease of the airways. These children usually will have an underlying congenital pulmonary anomaly, cystic fibrosis, or immunologic deficiency. Bronchiectasis also can result from chronic infection secondary to a neglected bronchial foreign body. The symptoms include a chronic cough, often productive of purulent secretions, recurrent pulmonary infection, and hemoptysis. The diagnosis is suggested by a CXR that shows increased bronchovascular markings in the affected lobe. Chest CT delineates bronchiectasis with excellent resolution. The preferred treatment for bronchiectasis is medical, consisting of antibiotics, postural drainage, and bronchodilator therapy, since many children with the disease show signs of airflow obstruction and bronchial hyperresponsiveness. Lobectomy or segmental resection is indicated for localized disease that has not responded appropriately to medical therapy. In severe cases, lung transplantation may be required to replace the terminally-damaged, septic lung.

Foreign Bodies FIG. 38-7. Arteriogram showing large systemic artery supply to intralobar sequestration of the left lower lobe.

diagnosis can be confirmed (e.g., by CT scan), resection is not necessary. Diagnosis of intralobar sequestration, on the other hand, is usually made after repeated infections manifested by cough, fever, and consolidation in the posterior basal segment of the left lower lobe. Increasingly the diagnosis is being made in the early months of life by US, and color Doppler often can be helpful in delineating the systemic arterial supply. Removal of the entire left lower lobe is usually necessary since the diagnosis often is made late after multiple infections. Occasionally the sequestered part of the lung can be removed segmentally. Prognosis is excellent.

Bronchogenic Cyst Bronchogenic cysts can occur anywhere along the respiratory tract from the neck to the lung parenchyma. They can present at any age. Histologically, they are hamartomatous, and usually consist of a single cyst lined with respiratory epithelium containing cartilage and smooth muscle. They are probably embryonic rests of foregut origin that have been pinched off from the main portion of the developing tracheobronchial tree, and are closely associated in causation with other foregut duplication cysts arising from the esophagus. Bronchogenic cysts may be seen on prenatal US, but are discovered most often incidentally on postnatal CXR. Although they may be completely asymptomatic, bronchogenic cysts may produce symptoms, depending on their anatomic location. In the paratracheal region of the neck they can produce airway compression and respiratory distress. In the lung parenchyma, they may become infected and present with fever and cough. In addition they may cause obstruction of the bronchial lumen with distal atelectasis and infection. They may also cause mediastinal compression. Rarely, rupture of the cyst can occur. CXR usually shows a dense mass, and CT scan or magnetic resonance imaging (MRI) delineates the precise anatomic

The inherent curiosity of children, and their innate propensity to place new objects into their mouths to fully explore them, places them at great risk for aspiration. Aspirated objects can be found either in the airway or in the esophagus, and in both cases the results can be life threatening.

Airway Ingestion Aspiration of foreign bodies most commonly occurs in toddlers. Peanuts are the most common object that is aspirated, although other materials (e.g., popcorn) may also be involved. A solid foreign body often will cause air trapping, with hyperlucency of the affected lobe or lung seen especially on expiration. Oil from a peanut is irritating and may cause pneumonia. Delay in diagnosis can lead to atelectasis and infection. The most common anatomic location for a foreign body is the right main stem bronchus or the right lower lobe. The child usually will cough or choke while eating, but may then become asymptomatic. Total respiratory obstruction with tracheal foreign body may occur; however, respiratory distress is usually mild if present. A unilateral wheeze is often heard on auscultation. This wheeze often leads to an inappropriate diagnosis of asthma, and may delay the correct diagnosis for some time. CXR will show a radiopaque foreign body, but in the case of nuts, seeds, or plastic toy parts, the only clue may be nondeflation of the affected lobe on an expiratory film or fluoroscopy. Bronchoscopy confirms the diagnosis and allows removal of the foreign body. It can be a simple procedure or it may be extremely difficult, especially with a smooth foreign body that cannot be grasped easily, or one that has been retained for some time. The rigid bronchoscope should be used in all cases, and utilization of the optical forceps facilitates grasping the inhaled object. Epinephrine may be injected into the mucosa when the object has been present for a long period of time, which minimizes bleeding. Bronchiectasis may be seen as an extremely late phenomenon after repeated infections of the poorly aerated lung, and may require partial or total resection of the affected lobe.

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Esophagus Ingestion The most common foreign body found in the esophagus is a coin, followed by small toy parts. Toddlers are most commonly affected. The coin is retained in the esophagus at one of three locations: the cricopharyngeus, the area of the aortic arch, or the gastroesophageal junction; all areas of normal anatomic narrowing. Symptoms are variable depending on the anatomic position of the foreign body and the degree of obstruction. There is often a relatively asymptomatic period after ingestion. The initial symptoms are gastrointestinal and include dysphagia, drooling, and vomiting. The longer the foreign body remains in the esophagus, the greater the incidence of respiratory symptoms, which include cough, stridor, and wheezing. These findings may be interpreted as signs of upper respiratory infections. Objects that are present for a long period of time—particularly in children who have underlying neurologic impairment—may manifest as chronic dysphagia. The CXR is diagnostic in the case of a coin. A contrast swallow may be required for nonradiopaque foreign bodies. Coins lodged within the upper esophagus for less than 24 hours may be removed using Magill forceps. For all other situations, the treatment is by esophagoscopy, rigid or flexible, and removal of the foreign body. In the case of sharp foreign bodies such as open safety pins, extreme care is required on extraction to avoid injury to the esophagus. Rarely, esophagotomy is required for removal, particularly of sharp objects. Diligent follow-up is required after removal of foreign bodies, especially batteries, which can cause strictures, and sharp objects, which can injure the underlying esophagus.

ESOPHAGUS Esophageal Atresia and Tracheoesophageal Fistula Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are among the most gratifying pediatric surgical conditions to treat. In the distant past, nearly all infants born with EA or TEF died. In

A

B

C

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1939 Ladd and Leven achieved the first successful repair by ligating the fistula, placing a gastrostomy, and reconstructing the esophagus at a later time. Subsequently, Dr. Cameron Haight in Ann Arbor, Michigan, performed the first successful primary anastomosis for esophageal atresia, which remains the current approach for treatment of this condition. Despite the facts that there are several common varieties of this anomaly, and the underlying cause remains obscure, a careful approach consisting of meticulous perioperative care and attention to the technical detail of the operation can result in an excellent prognosis in most cases.

Anatomic Varieties The five major varieties of EA and TEF are shown in Fig. 38-8. The most commonly seen variety is EA with distal TEF (type C), which occurs in approximately 75–85% of the cases in most series. The next most frequent is pure EA (type A), occurring in 8 to 10% of patients, followed by TEF without EA (type E). This occurs in 5–8% of cases, and also is referred to as an H-type fistula, based on the anatomic similarity to that letter (Fig. 38-9). EA with fistula between both proximal and distal ends of the esophagus and trachea (type D) is seen in approximately 1–2% of cases, and type B, EA with TEF between proximal segments of esophagus and trachea, is seen in approximately 1% of all cases.

Etiology and Pathologic Presentation The esophagus and trachea share a common embryologic origin. They typically divide into separate tubes by approximately the thirty-sixth day of gestation. Failure of this occurrence can result in the spectrum of anomalies seen in Fig. 38-8. Recent studies have shed light on some of the molecular mechanisms underlying this condition. Mice deficient in the Sonic-hedgehog signaling pathway develop a phenotype that includes esophageal atresiatracheoesophageal fistula (EA-TEF), suggesting a role for this molecule in the pathogenesis of the anomaly in humans. In support of this theory, Sonic-hedgehog transcripts were absent in human esophageal samples obtained from infants with TEF. Similarly,

D

E

FIG. 38-8. The five varieties of esophageal atresia and tracheoesophageal fistula. A . Isolated esophageal atresia. B . Esophageal atresia with tracheoesophageal fistula between proximal segments of esophagus and trachea. C . Esophageal atresia with tracheoesophageal fistula between distal esophagus and trachea. D . Esophageal atresia with fistula between both proximal and distal ends of esophagus and trachea. E . Tracheoesophageal fistula without esophageal atresia (H-type fistula).

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FIG. 38-9. Barium esophagram showing H-type tracheoesophageal fistula (arrow).

tissue obtained from the fistula tract was found to express thyroid transcription factor one (TTF-1) and fibroblast growth factor (FGF10), suggesting that the fistula is of respiratory origin. Although a genetic basis for EA-TEF has not been definitively established, reports indicate that this anomaly may occur in several generations of the same family. Twin studies also demonstrate the presence of esophageal atresia in sets of dizygotic twins. Other congenital anomalies frequently occur in association with EA-TEF. These defects are known by the acronyms VATER or VACTERRL syndrome, which refers to vertebral (missing vertebra) and anorectal (imperforate anus) anomalies, cardiac defects (severe congenital cardiac disease), tracheoesophageal fistula, r enal anomalies (renal agenesis and renal anomalies), and r adial limb hyperplasia. In nearly 20% of infants born with esophageal atresia, some variant of congenital heart disease is present.

Clinical Presentation The anatomic variant of infants with EA-TEF predicts the clinical presentation. When the esophagus ends either as a blind pouch or as a fistula into the trachea (as in types A, B, C, or D), infants present with excessive drooling, followed by choking or coughing immediately after feeding. As a result, aspiration occurs through the fistula tract. As the neonate coughs and cries, air is transmitted through the fistula into the stomach, resulting in abdominal distention. As the abdomen distends, it becomes increasingly more difficult for the infant to breathe. This leads to further atelectasis, which compounds the pulmonary dysfunction. In patients with type C and D varieties, the regurgitated gastric juice passes through the fistula, where it collects in the trachea and lungs and leads to a chemical pneumonitis, which further exacerbates the pulmonary status. In many instances, the diagnosis is actually made by the nursing staff, who attempt to feed the baby and notice the accumulation of oral secretions. The diagnosis of esophageal atresia is confirmed by the inability to pass an orogastric tube into the stomach (Fig. 38-10). The dilated upper pouch may occasionally be seen on a plain chest radiograph. If a soft feeding tube is used, the tube will coil in the upper pouch, which provides further diagnostic certainty. An important alternative diagnosis that must be considered when an orogastric tube does not enter the stomach is that of an esophageal perforation. This problem can occur in infants after traumatic insertion of a nasogastric or

FIG. 38-10. Type C esophageal atresia with tracheoesophageal fistula. Note the catheter that is coiled in the upper pouch, and the presence of gas below the diaphragm, which confirms the presence of the tracheoesophageal fistula.

orogastric tube. In this instance, the perforation classically occurs at the level of the piriform sinus, and a false passage is created which prevents the tube from entering the stomach. Whenever there is any diagnostic uncertainty, a contrast study will confirm the diagnosis of EA and occasionally document the TEF. The presence of a TEF can be demonstrated clinically by finding air in the gastrointestinal tract. This can be proven at the bedside by percussion of the abdomen, and confirmed by obtaining a plain abdominal radiograph. Occasionally, a diagnosis of EA-TEF can be suspected prenatally on ultrasound evaluation. Typical features include failure to visualize the stomach and the presence of polyhydramnios. These findings reflect the absence of efficient swallowing by the fetus. In a child with esophageal atresia, it is important to identify whether coexisting anomalies are present. These include cardiac defects in 38%, skeletal defects in 19%, neurologic defects in 15%, renal defects in 15%, anorectal defects in 8%, and other abnormalities in 13%. Examination of the heart and great vessels with echocardiography is important to exclude cardiac defects, as these are often the most important predictors of survival in these infants. The echocardiogram also demonstrates whether the aortic arch is left sided or right sided, which may influence the approach to surgical repair. Vertebral anomalies are assessed by plain radiography, and a spinal ultrasound is obtained if any are detected. A patent anus should be confirmed clinically. The kidneys in a newborn may be assessed clinically by palpation. An ultrasound of the abdomen will demonstrate the presence of renal anomalies, which should be suspected in the child who fails to make urine. The presence of extremity anomalies is suspected when there are missing digits, and confirmed by plain radiographs of the hands, feet, forearms, and legs. Rib anomalies may also be present. These may include the presence of a thirteenth rib.

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Initial Management The initial treatment of infants with esophageal atresiatracheoesophageal fistula includes attention to the respiratory status, decompression of the upper pouch, and appropriate timing of surgery. Because the major determinant of poor survival is the presence of other severe anomalies, a search for other defects including congenital cardiac disease is undertaken in a timely fashion. The initial strategy after the diagnosis is confirmed is to place the neonate in an infant warmer with the head elevated at least 30 degrees. A sump catheter is placed in the upper pouch on continuous suction. Both of these strategies are designed to minimize the degree of aspiration from the esophageal pouch. When saliva accumulates in the upper pouch and is aspirated into the lungs, coughing, bronchospasm, and desaturation episodes can occur, which may be minimized by ensuring the patency of the sump catheter. Intravenous antibiotic therapy is initiated, and warmed electrolyte solution is administered. Where possible, the right upper extremity is avoided as a site to start an intravenous line, as this location may interfere with positioning of the patient during the surgical repair. The timing of repair is influenced by the stability of the patient. Definitive repair of the EA-TEF is rarely a surgical emergency. If the child is hemodynamically stable and is oxygenating well, definitive repair may be performed within 1 to 2 days after birth. This allows for a careful determination of the presence of coexisting anomalies and for selection of an experienced anesthetic team.

Management in the Preterm Infant The ventilated, premature neonate with EA-TEF and associated hyaline membrane disease represents a patient who may develop severe pulmonary disease. TEF can worsen the fragile pulmonary status as a result of recurrent aspiration through the fistula, and of increased abdominal distention, which impairs lung expansion. Moreover, the elevated airway pressure that is required to ventilate these patients can worsen the clinical course by forcing air through the fistula into the stomach, thereby exacerbating the degree of abdominal distention and compromising lung expansion. In this situation, the first priority is to minimize the degree of positive pressure needed to adequately ventilate the child. This can be accomplished using HFOV. If the gastric distention becomes severe, a gastrostomy tube should be placed. This procedure can be performed at the bedside under local anesthetic, if necessary. The dilated, air-filled stomach can easily be accessed through an incision in the left upper quadrant of the abdomen. Once the gastrostomy tube is placed, and the abdominal pressure is relieved, the pulmonary status can paradoxically worsen. This is because the ventilated gas may pass preferentially through the fistula, which is the path of least resistance, and bypass the lungs thereby worsening the hypoxemia. To correct this problem, the gastrostomy tube may be placed under water seal, elevated, or intermittently clamped. If these maneuvers are to no avail, ligation of the fistula may be required. This procedure can be performed in the neonatal intensive care unit if the infant is too unstable to be transported to the operating room. These interventions allow for the infant’s underlying hyaline membrane disease to improve, for the pulmonary secretions to clear, and for the infant to reach a period of stability so that definitive repair can be performed.

Primary Surgical Correction In a stable infant, definitive repair is achieved through performance of a primary esophagoesophagostomy. The infant is brought to the operating room, intubated, and placed in the lateral decubitus position with the right side up in preparation for a right posterolateral

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thoracotomy. If a right-sided arch was determined previously by echocardiography, consideration is given to performing the repair through the left chest, although most surgeons believe that the repair can be performed safely from the right side as well. Bronchoscopy may be performed to exclude the presence of additional, upper pouch fistulae in cases of esophageal atresia (i.e., differentiation of types B, C, and D), and identification of a laryngeotracheoesophageal cleft. The operative technique for primary repair is as follows (Fig. 38-11). A retropleural approach is generally used, as this technique prevents widespread contamination of the thorax if a postoperative anastomotic leak occurs. The sequence of steps includes: 1. Mobilization of the pleura to expose the structures in the posterior mediastinum. 2. Division of the fistula and closure of the tracheal opening. 3. Mobilization of the upper esophagus sufficiently to permit an anastomosis without tension, and to determine whether a fistula is present between the upper esophagus and the trachea. Forward pressure by the anesthesia staff on the sump drain in the pouch can greatly facilitate dissection at this stage of the operation. Care must be taken when dissecting posteriorly to avoid violation of either the lumen of the trachea or esophagus. 4. Mobilization of the distal esophagus. This needs to be performed judiciously to avoid devascularization, since the blood supply to the distal esophagus is segmental from the aorta. Most of the esophageal length is obtained from mobilizing the upper pouch, since the blood supply travels via the submucosa from above. 5. Performing a primary esophagoesophageal anastomosis. Most surgeons perform this procedure in a single layer using 5-0 sutures. If there is excess tension, the muscle of the upper pouch can be circumferentially incised without compromising blood supply to increase its length. Many surgeons place a transanastomotic feeding tube in order to institute feeds in the early postoperative period. 6. A retropleural drain is placed, and the incision is closed in layers.

Postoperative Course The postoperative management strategy of patients with EA-TEF is influenced to a great degree by the preference of the individual surgeon and the institutional culture. Many surgeons prefer not to leave the infants intubated postoperatively, to avoid the effects of positive pressure on the site of tracheal closure. However, it may not be possible in babies with preoperative lung disease either from prematurity or pneumonia, or when there is any cord edema. When a transanastomotic tube is placed, feeds are begun slowly in the postoperative period. Some surgeons institute parenteral nutrition for several days, using a central line. The retropleural drain is assessed daily for the presence of saliva, indicating an anastomotic leak. Many surgeons obtain a contrast swallow 1 week after repair to assess the caliber of the anastomosis and to determine whether a leak is present. If there is no leak, feedings are started.

Complications of Surgery Anastomotic leakage occurs in 10 to 15% of patients, and may be seen either in the immediate postoperative period, or after several days. Early leakage is manifested by a new pleural effusion, pneumothorax, and sepsis, and requires immediate exploration. In these circumstances, the anastomosis may be completely disrupted, possibly due to excessive tension. Revision of the anastomosis may be possible. If not, cervical esophagostomy and gastrostomy placement is required, with a staged procedure to reestablish esophageal continuity. Anastomotic leakage that is detected after several days usually heals without intervention, particularly if a retropleural approach is used. Under these circumstances, broad-spectrum antibiotics, pulmonary toilet, and optimization of nutrition are important. After

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Azygous Vein Esophagus

Esophagus

Azygous Vein

A

B

C

D

E

FIG. 38-11. Primary repair of type C tracheoesophageal fistula. A . Right thoracotomy incision. B . Azygos vein transected, proximal and distal esophagus demonstrated, and fistula identified. C . Tracheoesophageal fistula transected and defect in trachea closed. D . End-to-end anastomosis between proximal and distal esophagus (posterior row). E . Completed anastomosis.

approximately a week or so, a repeat esophagram should be performed, at which time the leakage may have resolved. Strictures are not infrequent (10 to 20%), particularly if a leak has occurred. A stricture may become apparent at any time, from the early postoperative period to months or years later. It may present as choking, gagging, or failure to thrive, but often becomes clinically apparent with the transition to eating solid food. A contrast swallow or esophagoscopy is confirmatory, and simple dilatation is usually corrective. Occasionally, repeated dilatations are required. These may be performed in a retrograde fashion, during which a silk suture is placed into the oropharynx and delivered from the esophagus through a gastrostomy tube. Tucker dilators are then tied to the suture and passed in a retrograde fashion from the gastrostomy tube and delivered out of the oropharnyx. Increasing sizes are used, and the silk is replaced at the end of the procedure, where it is taped to the side of the face at one end, and to the gastrostomy tube at the other. “Recurrent” tracheoesophageal fistula may represent a missed upper pouch fistula or a true recurrence. This may occur after an anastomotic disruption, during which the recurrent fistula may heal spontaneously. Otherwise, reoperation may be required. Recently, the use of fibrin glue has been successful in treating recurrent fistulas, although long-term follow-up is lacking. Gastroesophageal reflux commonly occurs after repair of EA-TEF, potentially due to alterations in esophageal motility

and the anatomy of the gastroesophageal junction. The clinical manifestations of such reflux are similar to those seen in other infants with primary gastroesophageal reflux disease (GERD). A loose antireflux procedure, such as a Nissen fundoplication, is used to prevent further reflux, but the child may have feeding problems after antireflux surgery as a result of the innate dysmotility of the distal esophagus. The fundoplication may be safely performed laparoscopically in experienced hands, although care should be taken to ensure that the wrap is not excessively tight.

Special Circumstances Patients with type E TEFs (also called H-type) most commonly present beyond the newborn period. Presenting symptoms include recurrent chest infections, bronchospasm, and failure to thrive. The diagnosis is suspected using barium esophagography, and confirmed by endoscopic visualization of the fistula. Surgical correction is generally possible through a cervical approach, and requires mobilization and division of the fistula. Outcome usually is excellent. Patients with duodenal atresia and EA-TEF may require urgent treatment due to the presence of a closed obstruction of the stomach and proximal duodenum. In stable patients, treatment consists of repair of the esophageal anomaly and correction of the duodenal atresia if the infant is stable during surgery. If not, a staged approach should be utilized, consisting of ligation of the fistula and placement

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of a gastrostomy tube. Definitive repair can then be performed at a later time. Primary esophageal atresia (type A) represents a challenging problem, particularly if the upper and lower ends are too far apart for an anastomosis to be created. Under these circumstances, treatment strategies include placement of a gastrostomy tube and performing serial bougienage to increase the length of the upper pouch. Occasionally, when the two ends cannot be brought safely together, esophageal replacement is required, using either a gastric pull-up or colon interposition (see below).

Outcome Various classification systems have been utilized to predict survival in patients with EA-TEF and to stratify treatment. A system devised by Waterston in 1962 was used to stratify neonates based on birth weight, the presence of pneumonia, and the identification of other congenital anomalies. In response to advances in neonatal care, the surgeons from the Montreal Children’s Hospital proposed a new classification system in 1993. In the Montreal experience only two characteristics independently affected survival: preoperative ventilator dependence and associated major anomalies. Pulmonary disease as defined by ventilator dependence, appeared to be more accurate than pneumonia. When the two systems were recently compared, the Montreal system more accurately identified children at highest risk. Spitz and colleagues recently analyzed risk factors in infants with EA-TEF who died. Two criteria were found to be important predictors of outcome: birth weight less than 1500 g and the presence of major congenital cardiac disease. A new classification for predicting outcome in esophageal atresia was therefore proposed as follows: group I: birth weight ≥1500 g, without major cardiac disease, survival 97% (283 of 293); group II: birth weight 25% of spleen). Grade V: Shattered spleen; hilar vascular injury that devascularizes spleen.

surgery are similar to those for splenic injury and primarily involve hemodynamic instability. The intraoperative considerations in the management of massive hepatic injury are similar in children and adults. Renal contusions may occur after significant blunt abdominal trauma. Nonoperative management is usually successful, unless patients are unstable due to active renal bleeding. It is important to confirm the presence of a normal contralateral kidney at the time of surgery.

FETAL INTERVENTION One of the most exciting developments in the field of pediatric surgery has been the emergence of fetal surgery. The performance of a fetal intervention is justified when a defect is present that would cause devastating consequences to the infant if left uncorrected. For the vast majority of congenital anomalies, postnatal surgery is the preferred modality. However, in specific circumstances, fetal surgery may offer the best possibility for a successful outcome. The decision to perform a fetal intervention requires careful patient selection, as well as a multidisciplinary center that is dedicated to the surgical care of the fetus and the mother. Patient selection is dependent in part on highly accurate prenatal imaging, which includes ultrasound and MRI. At the present time, fetal surgery is performed at a few centers in North America, although this number is increasing. Significant risks may be associated with the performance of a fetal surgical procedure, to both the mother and the fetus. From the maternal viewpoint, open fetal surgery may lead to uterine bleeding due to the uterine relaxation required during the procedure. The Table 38-7 Liver Injury Grading System Grade I: Capsular tear 75% of hepatic lobe or >3 Couinaud segments within a single lobe; injury to retrohepatic vena cava. source: Reproduced with permission from Moore EE, Cogbill TH, Malangoni MA, et al: Organ injury scaling. Surg Clin North Am 75:293, 1995.

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FIG. 38-42. Abdominal CT scan of a child demonstrating a grade III liver laceration (arrows).

long-term effects on subsequent pregnancies remain to be established. For the fetus, in utero surgery carries the risk of premature labor and amniotic fluid leakage. As a result, these procedures are performed only when the expected benefit of fetal intervention outweighs the risk to the fetus of standard postnatal care.

Surgery for Lower Urinary Tract Obstruction Lower urinary tract obstruction refers to a group of diseases characterized by obstruction of the distal urinary system. Common causes include the presence of posterior urethral valves and urethral atresia, as well as other anomalies of the urethra and bladder. The pathologic effects of lower urinary tract obstruction lie in the resultant massive bladder distention that occurs, which can lead to reflux hydronephrosis. This may result in oligohydramnios, and cause limb contractures, facial anomalies (Potter facies), and pulmonary hypoplasia. Carefully selected patients with lower urinary tract obstruction may benefit from vesicoamniotic shunting. By relieving the obstruction and improving renal function, fetal growth and lung development may be preserved.

Fetal Surgery for Congenital Diaphragmatic Hernia Given the high mortality associated with the most severe cases of CDH, tremendous efforts have been undertaken to determine whether fetal intervention could improve the outcome of this disease. In 1990, Harrison and colleagues reported the first open fetal repair for CDH. The high morbidity of the open technique led to the development of fetal tracheal occlusion as a therapeutic approach. This was based on the observation that tracheal occlusion could lead to increased lung growth and reduction of the intrathoracic viscera in animal models. Tracheal occlusion can be achieved in utero by placement of clips that are removed at the time of delivery. Despite initial enthusiasm for this approach, a recent randomized trial that compared fetal tracheal occlusion with standard postnatal care for left-sided CDH showed no improvement in survival for patients treated with tracheal occlusion.

Fetal Surgery for Myelomeningocele Myelomeningocele refers to a spectrum of anomalies in which portions of the spinal cord are uncovered by the spinal column. This

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FIG. 38-43. The EXIT (ex-utero intrapartum treatment) procedure in a baby at 34 weeks’ gestation with a large cervical teratoma. Intubation is performed while the fetus is on placental support.

leaves the neural tissue exposed to the injurious effects of the amniotic fluid, as well as to trauma from contact with the uterine wall. Nerve damage ensues, resulting in varying degrees of lower extremity paralysis, as well as bowel and bladder dysfunction. Initial observations indicated that the extent of injury progressed throughout the pregnancy, which provided the rationale for fetal intervention. The current in utero approach for the fetus with myelomeningocele has focused on obtaining coverage of the exposed spinal cord. Initial results have shown a decrease in the development of obstructive hydrocephalus requiring ventriculoperitoneal shunting. A National Institutes of Health–sponsored trial is currently underway, in which patients are randomized to receive either in utero coverage of the spinal cord or standard postnatal care. The effects of the treatment approach on neurologic function can then be determined.

The Ex-Utero Intrapartum Treatment Procedure The EXIT procedure is utilized in circumstances in which an airway obstruction is predicted at the time of delivery, due to the presence of a large neck mass such as a cystic hygroma or teratoma (Fig. 38-43), or congenital tracheal stenosis. The success of the procedure is dependent on the maintenance of uteroplacental perfusion for a sufficient duration to secure the airway. To achieve this, deep uterine relaxation is obtained during a cesarean section under general anesthesia. Uterine perfusion with warmed saline also promotes relaxation and blood flow to the placenta. On average, between 20 and 30 minutes of placental perfusion can be achieved. The fetal airway is secured either by placement of an orotracheal tube, or performance of a tracheostomy. Once the airway is secured, the cord is cut, and a definitive procedure may be performed to relieve the obstruction postnatally. Bibliography Ahuja AT, King AD, et al: Thyroglossal duct cysts: Sonographic appearances in adults. Am J Neuroradiol 20:579, 1999. Andersen B, Kallehave F, et al: Antibiotics versus placebo for prevention of postoperative infection after appendicectomy. Cochrane Database Syst Rev 2:CD001439. Anderson KD, Rouse TM, et al: A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 323:637, 1990.

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Azarow K, Messineo A, et al: Congenital diaphragmatic hernia—a tale of two cities: The Toronto experience. J Pediatr Surg 32:395, 1997. Billmire D, Vinocur C, et al: Malignant mediastinal germ cell tumors: An intergroup study. J Pediatr Surg 36:18, 2001. Bohn D: Congenital diaphragmatic hernia. Am J Respir Crit Care Med 166:911, 2002. Boloker J, Bateman DA, et al: Congenital diaphragmatic hernia in 120 infants treated consecutively with permissive hypercapnea/spontaneous respiration/elective repair. J Pediatr Surg 37:357, 2002. Bouchard S, Johnson MP, et al: The EXIT procedure: Experience and outcome in 31 cases. J Pediatr Surg 37:418, 2002. Branstetter BF, Weissman JL, et al: The CT appearance of thyroglossal duct carcinoma. Am J Neuroradiol 21:1547, 2000. Bratton S, Annich G: Packed red blood cell transfusions for critically ill pediatric patients: When and for what conditions? J Pediatr 142:95, 2003. Breneman JC, Lyden E, et al: Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma—A report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 21:78, 2003. Bruner JP, Tulipan N, et al: Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA 282:1819, 1999. Chertin B, De Caluw´e D, et al: Is contralateral exploration necessary in girls with unilateral inguinal hernia? J Pediatr Surg 38:756, 2003. Cohen J, Schanen NC: Branchial cleft anomaly, congenital heart disease, and biliary atresia: Goldenhar complex or Lambert syndrome? Genet Couns 11:153, 2000. Cohn SL, London WB, et al: MYCN expression is not prognostic of adverse outcome in advanced-stage neuroblastoma with nonamplified MYCN. J Clin Oncol 18:3604, 2000. Coppes MJ, Haber DA, et al: Genetic events in the development of Wilms’ tumor. N Engl J Med 331:586, 1994. Cotterill SJ, Pearson ADJ, et al: Clinical prognostic factors in 1277 patients with neuroblastoma: Results of The European Neuroblastoma Study Group Survey 1982–1992. Eur J Cancer 36:901, 2000. Crystal P, Hertzanu Y, et al: Sonographically guided hydrostatic reduction of intussusception in children. J Clin Ultrasound 30:343, 2002. Dunn J, Fonkalsrud E, et al: Simplifying the Waterston’s stratification of infants with tracheoesophageal fistula. Am Surg 65:908, 1999. Ferrari A, Bisogno G, et al: Paratesticular rhabdomyosarcoma: Report from the Italian and German Cooperative Group. J Clin Oncol 20:449, 2002. Freedman AL, Johnson MP, et al: Long-term outcome in children after antenatal intervention for obstructive uropathies. Lancet 354:374, 1999. Geisler DP, Jegathesan S, et al: Laparoscopic exploration for the clinically undetected hernia in infancy and childhood. Am J Surg 182:693, 2001. Georgeson K: Laparoscopic-assisted pull-through for Hirschsprung’s disease. Semin Pediatr Surg 11:205, 2002. Georgeson K: Results of laparoscopic antireflux procedures in neurologically normal infants and children. Semin Laparosc Surg 9:172, 2002. Gollin GA, Abarbanell AA, et al: Peritoneal drainage as definitive management of intestinal perforation in extremely low-birth-weight infants. J Pediatr Surg 38:1814, 2003. Gorsler C, Schier F: Laparoscopic herniorrhaphy in children. Surg Endosc 17:571, 2003. Guthrie S, Gordon P, et al: Necrotizing enterocolitis among neonates in the United States. J Perinatol 23:278, 2003. Hackam DJ, Filler R, et al: Enterocolitis after the surgical treatment of Hirschsprung’s disease: Risk factors and financial impact. J Pediatr Surg 33:830, 1998. Hackam DJ, Potoka D, et al: Utility of radiographic hepatic injury grade in predicting outcome for children after blunt abdominal trauma. J Pediatr Surg 37:386, 2002. Hackam DJ, Reblock K, et al: The influence of Down’s syndrome on the management and outcome of children with Hirschsprung’s disease. J Pediatr Surg 38:946, 2003. Hackam DJ, Superina R, et al: Single-stage repair of Hirschsprung’s disease: A comparison of 109 patients over 5 years. J Pediatr Surg 32:1028, 1997.

Harrison MR: Fetal surgery: Trials, tribulations, and turf. J Pediatr Surg 38:275, 2003. Harrison MR, Keller RL, et al: A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med 349:1916, 2003. Harrison MR, Sydorak RM, et al: Fetoscopic temporary tracheal occlusion for congenital diaphragmatic hernia: Prelude to a randomized, controlled trial. J Pediatr Surg 38:1012, 2003. Hedrick H, Flake A, et al: History of fetal diagnosis and therapy: Children’s Hospital of Philadelphia experience. Fetal Diagn Ther 18:65, 2003. Hirschl RB, Philip WF, et al: A prospective, randomized pilot trial of perfluorocarbon-induced lung growth in newborns with congenital diaphragmatic hernia. J Pediatr Surg 38:283, 2003. Johnson MP, Sutton LN, et al: Fetal myelomeningocele repair: Short-term clinical outcomes. Am J Obstet Gynecol 189:482, 2003. Kalapurakal J, Li S, et al: Influence of radiation therapy delay on abdominal tumor recurrence in patients with favorable histology Wilms’ tumor treated on NWTS-3 and NWTS-4: A report from the National Wilms’ Tumor Study Group. Int J Radiat Oncol Biol Phys 57:495, 2003. Kamata S, Ishikawa S, et al: Prenatal diagnosis of abdominal wall defects and their prognosis. J Pediatr Surg 31:267, 1996. Katzenstein HM, Krailo MD, et al: Hepatocellular carcinoma in children and adolescents: Results from the Pediatric Oncology Group and the Children’s Cancer Group Intergroup Study. J Clin Oncol 20:2789, 2002. Kim HB, Lee PW, et al: Serial transverse enteroplasty for short bowel syndrome: A case report. J Pediatr Surg 38:881, 2003. Konkin D, O’hali W, et al: Outcomes in esophageal atresia and tracheoesophageal fistula. J Pediatr Surg 38:1726, 2003. Langer J, Durrant A, et al: One-stage transanal Soave pullthrough for Hirschsprung disease: A multicenter experience with 141 children. Ann Surg 238:569, 2003. Levitt MA, Ferraraccio D, et al: Variability of inguinal hernia surgical technique: A survey of North American pediatric surgeons. J Pediatr Surg 37:745, 2002. Lintula H, Kokki H, et al: Single-blind randomized clinical trial of laparoscopic versus open appendicectomy in children. Br J Surg 88:510, 2001. Lipshutz G, Albanese C, et al: Prospective analysis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia. J Pediatr Surg 32:1634, 1997. Little D, Rescorla F, et al: Long-term analysis of children with esophageal atresia and tracheoesophageal fistula. J Pediatr Surg 38:852, 2003. Marianowski R, Ait Amer JL, et al: Risk factors for thyroglossal duct remnants after Sistrunk procedure in a pediatric population. Int J Pediatr Otorhinolaryngol 67:19, 2003. Maris JM, Weiss MJ, et al: Loss of heterozygosity at 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: A Children’s Cancer Group Study. J Clin Oncol 18:1888, 2000. Meyers RL, Book LS, et al: High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 38:406, 2003. Miyano T, Yamataka A, et al: Hepaticoenterostomy after excision of choledochal cyst in children: A 30-year experience with 180 cases. J Pediatr Surg 31:1417, 1996. Molik KA, West KW, et al: Portal venous air: The poor prognosis persists. J Pediatr Surg 36:1143, 2001. Moss R, Dimmitt R, et al: A meta-analysis of peritoneal drainage versus laparotomy for perforated necrotizing enterocolitis. J Pediatr Surg 36:1210, 2001. Moyer V, Moya F, et al: Late versus early surgical correction for congenital diaphragmatic hernia in newborn infants. Cochrane Database Syst Rev 3:CD001695, 2002. Nadler E, Stanford A, et al: Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: Interleukin-11 mRNA expression inversely correlates with extent of disease. J Pediatr Surg 36:1122, 2001. Neville HL, Andrassy RJ, et al: Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 35:961, 2000.

38/PEDIATRIC SURGERY Nio M, Ohi R, et al: Five- and 10-year survival rates after surgery for biliary atresia: A report from the Japanese Biliary Atresia Registry. J Pediatr Surg 38:997, 2003. Olutoye OO, Coleman BG, et al: Prenatal diagnosis and management of congenital lobar emphysema. J Pediatr Surg 35:792, 2000. Ortega JA, Douglass EC, et al: Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children’s Cancer Group and the Pediatric Oncology Group. J Clin Oncol 18:2665, 2000. Panesar J, Higgins K, et al: Nontuberculous mycobacterial cervical adenitis: A ten-year retrospective review. Laryngoscope 113:149, 2003. Pedersen A, Petersen O, et al: Randomized clinical trial of laparoscopic versus open appendicectomy. Br J Surg 88:200, 2001. Pena A, Guardino K, et al: Bowel management for fecal incontinence in patients with anorectal malformations. J Pediatr Surg 33:133, 1998. Poenaru D, Laberge J, et al: A new prognostic classification for esophageal atresia. Surgery 113:426, 1993. Potoka DA, Schall LC, et al: Risk factors for splenectomy in children with blunt splenic trauma. J Pediatr Surg 37:294, 2002. Potoka D, Schall L, et al: Improved functional outcome for severely injured children treated at pediatric trauma centers. J Trauma 51:824, 2001. Powers CJ, Levitt MA, et al: The respiratory advantage of laparoscopic Nissen fundoplication. J Pediatr Surg 38:886, 2003. Pritchard-Jones K: Controversies and advances in the management of Wilms’ tumour. Arch Dis Child 87:241, 2002. Puapong D, Kahng D, et al: Ad libitum feeding: Safely improving the costeffectiveness of pyloromyotomy. J Pediatr Surg 37:1667, 2002. Quinton AE, Smoleniec JS: Congenital lobar emphysema—the disappearing chest mass: Antenatal ultrasound appearance. Ultrasound Obstet Gynecol 17:169, 2001. Rosen NG, Hong AR, et al: Rectovaginal fistula: A common diagnostic error with significant consequences in girls with anorectal malformations. J Pediatr Surg 37:961, 2002. Rothenberg S: Laparoscopic Nissen procedure in children. Semin Laparosc Surg 9:146, 2002. Samuel M, McCarthy L, et al: Efficacy and safety of OK-432 sclerotherapy for giant cystic hygroma in a newborn. Fetal Diagn Ther 15:93, 2000. Sandler A, Ein S, et al: Unsuccessful air-enema reduction of intussusception: Is a second attempt worthwhile? Pediatr Surg Int 15:214, 1999.

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Schier F, Montupet P, et al: Laparoscopic inguinal herniorrhaphy in children: A three-center experience with 933 repairs. J Pediatr Surg 37:395, 2002. Section on Hematology/Oncology: Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. Pediatrics 99:139, 1997. Shamberger R, Guthrie K, et al: Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4. Ann Surg 229:292, 1999. Shimada H, Ambros I, et al: The International Neuroblastoma Pathology Classification (the Shimada system). Cancer 86:364, 1999. Simons SHP, van Dijk M, et al: Routine morphine infusion in preterm newborns who received ventilatory support: A randomized controlled trial. JAMA 290:2419, 2003. Soffer SZ, Rosen NG, et al: Cloacal exstrophy: A unified management plan. J Pediatr Surg 35:932, 2000. Spitz L, Kiely E, et al: Oesophageal atresia: At-risk groups for the 1990s. J Pediatr Surg 29:723, 1994. Strauss RA, Balu R, et al: Gastroschisis: The effect of labor and ruptured membranes on neonatal outcome. Am J Obstet Gynecol 189:1672, 2003. Suzuki N, Tsuchida Y, et al: Prenatally diagnosed cystic lymphangioma in infants. J Pediatr Surg 33:1599, 1998. Teich S, Barton D, et al: Prognostic classification for esophageal atresia and tracheoesophageal fistula: Waterston versus Montreal. J Pediatr Surg 32:1075, 1997. Teitelbaum D, Coran A: Reoperative surgery for Hirschsprung’s disease. Semin Pediatr Surg 12:124, 2003. Thibeault DW, Olsen SL, et al: Pre-ECMO predictors of nonsurvival in congenital diaphragmatic hernia. J Perinatol 22:682, 2002. Tolia V, Wureth A, et al: Gastroesophageal reflux disease: Review of presenting symptoms, evaluation, management, and outcome in infants. Dig Dis Sci 48:1723, 2003. Tulipan N, Sutton L, et al: The effect of intrauterine myelomeningocele repair on the incidence of shunt-dependent hydrocephalus. Pediatr Neurosurg 38:27, 2003. Wenzler D, Bloom D, et al: What is the rate of spontaneous testicular descent in infants with cryptorchidism? J Urol 171:849, 2004. Wildhaber B, Coran A, et al: The Kasai portoenterostomy for biliary atresia: A review of a 27-year experience with 81 patients. J Pediatr Surg 38:1480, 2003. Wilson J, Lund D, et al: Congenital diaphragmatic hernia—a tale of two cities: The Boston experience. J Pediatr Surg 32:401, 1997.

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CHAPTER

39

Urology Hyung L. Kim and Arie Belldegrun

Anatomy The Kidney and Ureter Adrenal Gland Bladder and Urethra Prostate and Seminal Vesicle Testis and Epididymis Penis Signs and Symptoms Symptoms Related to Voiding Urinary Incontinence Hematuria Other Findings Physical Examination Examination of the Penis, Scrotum, and Testis Prostate Exam Laboratory Examination Examination of the Urine Urine Culture Tests of Kidney Function

Work-Up Treatment Testis Cancer Penile Cancer Urologic Infections Cystitis Pyelonephritis Xanthogranulomatous Pyelonephritis Fungal Infections Prostatitis Urinary Incontinence Normal Voiding Physiology Urodynamics Stress Urinary Incontinence Urge Incontinence Total Incontinence Overflow Incontinence Trauma

Imaging of Kidney and Ureter Imaging of the Bladder and Urethra Testicular Ultrasound Renal Scan

Kidney and Ureter Bladder Urethra Posterior Urethra Anterior Urethra Penis Testis

Benign Prostatic Hyperplasia

Stone Disease

Etiology Natural History Medical Therapy Surgical Management

Etiology Acute Kidney Stone Presentation Radiologic Work-Up Management Medical Management Stone Composition Medical Treatment

Radiologic Studies of the Urinary System

Urologic Oncology Renal Cell Carcinoma Epidemiology Presentation and Prognosis Work-Up Treatment Bladder Cancer Epidemiology Presentation Work-Up Treatment of Superficial Bladder Cancer (Ta, T1, CIS) Treatment of Muscle-Invasive Bladder Cancer (T2, T3, T4) Prostate Cancer Epidemiology Prostate Cancer Screening

Sexual Dysfunction Erectile Dysfunction Peyronie’s Disease Priapism Infertility Pediatric Urology Hydronephrosis Ureteropelvic Junction Obstruction Vesicoureteral Reflux Ureterocele Posterior Urethral Valve

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The Penis Hypospadias Phimosis Paraphimosis The Testicle Testicular Torsion Hydrocele

ANATOMY The Kidney and Ureter The organs of the urinary system, which include the kidney, ureter, and bladder, are located in the retroperitoneum.1−3 The kidneys are paired organs surrounded by perirenal fat and Gerota’s fascia (Fig. 39-1). The superior aspect of the kidney is contained within the lower thoracic cavity at the level of the tenth rib. The posterior aspect of the kidney lies against the quadratus lumborum, and the renal hilum lies against the psoas muscle. The upper pole of the right kidney abuts the liver. Anteriorly, the right kidney is adjacent to the duodenum and hepatic flexure of the colon. The left kidney is bounded anteriorly by the splenic flexure. The blood supply to the kidney comes from the renal artery. The right and left renal arteries come off the aorta just inferior to the takeoff of the superior mesenteric artery. The right renal artery passes posterior to the inferior vena cava. The renal veins are anterior to the renal arteries and drain into the inferior vena cava. The renal artery and vein are anterior to the renal pelvis and proximal ureter at the level of the renal hilum. In the kidney, the arteries are end-arteries, while the veins anastomose freely. The left

adrenal vein and left gonadal vein drain into the left renal vein, while on the right, these same vessels drain directly into the vena cava. The urine formed in the kidney drains into the collecting system and passes into the renal pelvis. The renal pelvis drains urine into the bladder through the ureter. Ureteral peristalsis originates from pacemaker cells located in the collecting system of the kidney. Along the course of the ureter in the retroperitoneum, the ureteral lumen is relatively narrower at the ureteral pelvic junction, at the pelvic brim where the ureter crosses the common iliac vessels and at the ureteral vesical junction. In patients passing a kidney stone, these areas represent common sites of impaction.

Adrenal Gland The adrenal glands are endocrine organs that lie superomedial to the kidneys. They are surrounded by the perirenal fat and contained within Gerota’s fascia. The right adrenal gland is positioned posterolateral to the inferior vena cava and tends to be more superior in relation to the left adrenal gland. The arterial blood supply to the adrenal glands is provided primarily by the inferior phrenic artery. On the right, the primary venous drainage is directly to the inferior vena cava. On the left, the primary venous drainage is to the left renal vein.

Bladder and Urethra The bladder is a hollow, muscular organ adapted for storing and expelling urine. When it is empty, it lies posterior to the pubic symphysis in the pelvis and is extraperitoneal. The dome of the bladder is covered with peritoneum, and when the bladder is full, it can

Superior mesenteric artery Adrenal Stomach Spleen Pancreas Colon Ileum

Ureter

Aorta

Kidney

Vena cava

Liver Colon Ileum

Bladder

Quadratus lumborum muscle Psoas muscle

FIG. 39-1. Relations of the kidneys, ureters, and bladder. Anterior regions of the kidney labeled with adjacent organs.

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Transition zone

Vas deferens

Urethra Ureter

Seminal vesicle

Peripheral zone

Prostate

Central zone FIG. 39-2. Relations of the prostate, seminal vesicles, and bladder.

rise into the abdomen and is palpable on physical examination. The normal bladder can store approximately 350 to 450 mL. The muscularis propria, also referred to as the bladder detrusor, forms the muscular wall of the bladder. Close to the urethra, the muscle fibers become organized into three layers: an inner longitudinal, middlecircular, and outer-longitudinal. The arterial blood supply to the bladder comes from the superior, middle, and inferior vesical arteries, which are all branches of the internal iliac artery. The venous return from the bladder drains into the internal iliac vein. In men, urinary continence is maintained by the internal and external sphincters. The internal sphincter, composed of smooth muscle, is formed by the middle circular layer of the bladder wall as it invests the prostate gland. Contraction of this sphincter during ejaculation prevents retrograde ejaculation by directing the semen toward the urethral meatus. The external sphincter surrounds the urethra at the level of the distal prostate gland and is composed of both smooth and striated muscle fibers. In women, the continence mechanism is quite different. There is no internal sphincter and the middle circular layer of the bladder muscularis, which is prominent in the male bladder neck, is not found. Continence is maintained by the resistance provided by the coaptation of the urethral mucosa and the external striated sphincter surrounding the distal two-thirds of the urethra. FIG. 39-4. Testis, epididymis, and vas deferens.

FIG. 39-3. Zonal anatomy of the prostate.

Prostate and Seminal Vesicle The prostate gland and the seminal vesicles are part of the male reproductive system (Fig. 39-2). Secretions from these two organs make up part of the male semen. The prostate surrounds the proximal urethra. The gland can be divided into several zones (Fig. 39-3). Most prostate cancers form in the peripheral zone. The central zone surrounds the ejaculatory ducts as they empty into the urethra at the verumontanum. Benign prostatic hyperplasia (BPH) is caused by enlargement of the transition zone surrounding the urethra. BPH, which is common in the elderly population, can lead to increased urinary resistance and voiding symptoms.

Testis and Epididymis The volume of an average testis is approximately 20 mL (Fig. 39-4). The testicles have two important functions: androgen and sperm production. The Leydig cells in the testis produce testosterone. The Sertoli cells support the maturation of spermatogenic cells into sperm. The Sertoli cells are also responsible for establishing a blood–testis barrier. The testicles are surrounded by several fascial layers that are embryologically derived from the same layers comprising the anterior abdominal wall (Fig. 39-5). The external spermatic fascia

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Skin

Dartos

External spermatic fascia

Cremasteric muscle

Internal spermatic fascia

Tunica vaginalis

Epididymis

Testis FIG. 39-5. The testicle and its surrounding layers.

is analogous to the external oblique. The cremasteric muscle envelops the spermatic cord and is analogous to the internal oblique and transversus abdominis. The internal spermatic fascia is analogous to the transversalis fascia. The visceral and parietal layers of the tunica vaginalis testis represent peritoneum that surrounded the testicle during its descent into the scrotum. The blood supply to the testicles is provided by three arteries: gonadal, cremasteric, and vasal. The gonadal artery branches directly from the aorta. The cremasteric artery branches from the inferior epigastric artery, and the vasal artery branches from the superior vesical artery. The venous drainage from the testicles forms the pampiniform plexus at the level of the spermatic cord. At the internal inguinal ring, the pampiniform plexus coalesces to form the gonadal vein, which drains into the inferior vena cava on the right and into the renal vein on the left. The epididymis is located on the posterolateral aspect of the testis. Spermatogenesis occurs in the seminiferous tubules of the testes. Mature sperm is conducted by the efferent ducts into the epididymis where they are stored. Under sympathetic stimulation, the sperm is conducted along the vas deferens during a process termed emission. The vas deferens is joined by the seminal vesicle to form the ejaculatory duct. The semen that is deposited into the urethra is carried along the urethra under somatic enervation during ejaculation.

Penis The penis is formed by three corpora bodies: two corpora cavernosa and a corpus spongiosum (Fig. 39-6). The corpus spongiosum surrounds the male urethra. The three corpora bodies are covered by the tunica albuginea. The next layer, going outward toward the skin, is Buck’s fascia. Buck’s fascia splits dorsally to envelop the neurovascular structures and splits ventrally to surround the corpora spongiosum. The superficial dartos fascia is just underneath the skin and is contiguous with the Colles fascia in the perineum and the Scarpa fascia in the abdominal wall. The base of the penis is supported by suspensory ligaments that attach to the linea alba and pubic symphysis.

The common penile artery is the terminal branch of the internal pudendal artery. It divides into three branches that supply blood to the penis. The cavernous arteries supply the corpora cavernosa. The bulbourethral branch supplies the glans, urethra, and corpus spongiosum. The dorsal arteries run in the neurovascular bundle enveloped by Buck’s fascia and supply the corpus spongiosum and urethra. Venous drainage from the penis is provided by the dorsal and cavernous veins, which join to form the internal pudendal vein. Sensory innervation is carried by the dorsal nerves that run with the dorsal vessels. Autonomic innervation is provided by the cavernous nerves that pierce the tunica albuginea to innervate the smooth muscles found in the corpora cavernosa.

SIGNS AND SYMPTOMS Symptoms Related to Voiding Symptoms related to voiding can be broadly categorized as irritative or obstructive. Specific irritative symptoms include dysuria, frequency, and urgency. These symptoms generally imply inflammation of the urethra, prostate, or bladder. Although irritative voiding symptoms are commonly caused by infection, they can also be caused by malignancy, and in patients with symptoms that persist after treatment with appropriate antibiotics, malignant processes such as transitional cell carcinoma must be ruled out. In symptomatic patients with no specific etiology, the diagnosis of interstitial cystitis or chronic nonbacterial prostatitis is often made. The pathophysiology of both these processes is poorly understood and results of available treatments are often unsatisfactory. Specific obstructive voiding symptoms include a weak urinary stream, urgency, frequency, hesitancy, intermittency, nocturia, and sense of incomplete emptying. Hesitancy refers to a delay in initiating a urinary stream and intermittency refers to repeated starting and stopping of the urine stream during voiding. The most common cause of obstructive voiding in men is benign prostatic hyperplasia.

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Seminal vesicle Amplulla of vas deferens BLADDER Vas deferens

Prostatic urethra Prostate

Lobules of prostate Ejactulatory ducts

Bulbourethral gland and orifice

Membranous urethra

Bulbous urethra

Urogenital diaphragm

Corpus cavernosum

Penile urethra

Prepuce

A

Corpus spongiosum

Glas penis Fossa navicularis

Superficial penile artery and vein Buck's fascia Dorsal nerve Deep dorsal vein Cavernous artery

FIG. 39-6. ( A ) Longitudinal and ( B ) cross-sectional anatomy of the penis. (A is reproduced with permission from Schwartz’s Textbook of General Surgery, 6th ed. New York: McGrawHill, 1994, p. 1728.)

Deep dorsal artery

Tunica albuginea

Corpus cavernosum

Urethra

Corpus spongiosum

B

Urethral strictures may also obstruct the bladder outlet and are often secondary to trauma, urethritis or previous instrumentation of the bladder.

Urinary Incontinence Urinary incontinence can be categorized as stress, urge, total, and overflow. Stress incontinence refers to incontinence associated with

an increase in intra-abdominal pressure. Patients often report leakage of urine when coughing, laughing, or during physical exertion. Stress incontinence is secondary to a decrease in the resistance provided by the urinary continence mechanisms and generally implies an anatomic disorder, such as an iatrogenic injury to the external sphincter in a male or prolapse of the bladder in a female. Urge incontinence is secondary to an involuntary contraction of the bladder

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and is accompanied by a sudden sense of needing to void. Urge incontinence may be secondary to inflammation and irritation of the bladder, or it may result from neurologic disorders such as a stroke or spinal cord injury. Total incontinence refers to a continuous leakage of urine and implies a fistula between the skin or vagina and the urinary tract, proximal to the sphincter mechanism. Women with a vesicovaginal fistula secondary to malignancy or trauma will complain of continuous leakage of urine. Overflow incontinence is secondary to an obstruction of the lower urinary tract. As urine builds up in the bladder, the intravesical pressure increases and overcomes the resistance provided by the urinary sphincter. All patients at risk for urinary tract obstruction who develop new-onset incontinence should be checked for urinary retention by postvoid bladder ultrasound or catheterization of the bladder.

Hematuria Patients with gross or microscopic hematuria, in the absence of obvious evidence of a urinary tract infection, need to be evaluated with upper and lower tract studies. On microscopic examination of the urine, more than five red blood cells per high power field in spun urine or more than two red blood cells per high power field in unspun urine is considered significant microscopic hematuria. Because hematuria can be intermittent, even a single documented episode of significant microscopic hematuria warrants a complete evaluation. The upper tract, which includes the kidney and ureter, should be evaluated with an intravenous pyelogram, CT scan, or retrograde pyelogram. The CT scan should be performed with intravenous contrast and delayed images should be obtained once the excreted contrast has filled the upper tract collecting system. The lower tract, which includes the bladder and urethra, should be evaluated by cystoscopy. The differential diagnosis for hematuria includes malignancies, infections, kidney stones, and trauma. Malignancies of the kidney and bladder classically present with painless hematuria. Patients with gross painless hematuria should be considered to have a urinary tract malignancy until proven otherwise. Infections involving the bladder or urethra are generally associated with symptoms of irritative voiding. Pyelonephritis is a clinical diagnosis based on findings of irritative voiding symptoms, fever, and flank pain. Kidney stones are associated with a colicky pain. The localization of the pain depends on the level of obstruction by the stone. An obstruction at the ureteropelvic junction will cause flank pain while obstruction of the lower ureter can produce colicky pain referred to the lower abdomen or groin.

Other Findings Other complaints and findings related to the urinary system include urethral discharge, hematospermia, and pneumaturia. Urethral discharge is a common complaint that usually results from infection with Neisseria gonorrhoeae or Chlamydia trachomatis. The discharge is often associated with dysuria. Hematospermia refers to blood in the ejaculated semen and is caused by inflammation of seminal vesicles or prostate. As a general rule, hematospermia is self-limiting and does not require further evaluation or treatment. Pneumaturia refers to air in the voided urine. The finding of pneumaturia can be confirmed by having the patient void in a tub with the urethral meatus submerged. Pneumaturia may result from recent instrumentation of the bladder or from a fistula between the urinary tract and the intestine.

PHYSICAL EXAMINATION Examination of the Penis, Scrotum, and Testis The physical examination of a male patient should be performed with the patient standing and the physician seated on a stool. Initially, the skin of the penis, scrotum, and the surrounding inguinal region should be visually inspected. The testicles should be palpated for masses or tenderness and the size of the testicles should be noted. The epididymis can be palpated on the posterolateral surface of the testicles. Any nodules should be noted and an effort should be made to determine if palpable lesions are associated with the testis or the epididymis. The vas deferens can be felt by gently compressing the scrotum above the testicles. Hydroceles represent a buildup of fluid between the two layers of the tunica vaginalis. If the testicles are enlarged by a hydrocele, the presence of a hydrocele sac can be confirmed by transilluminating the sac with a penlight. Varicoceles may be palpable in the scrotum and represent dilated veins, which are analogous to varicose veins found on the leg. The penis should be gently massaged to express any urethral discharge. The penile shaft and urethra should be palpated along the length of the penis. Any nodules or fibrotic plaques on the corporal bodies should be noted.

Prostate Exam The prostate is examined with the patient leaning over an examination bench and resting on his elbows. Alternatively, the patient can be lying in a lateral decubitus position. Initially, the anus and surrounding area is visually inspected. Using lubrication, the index finger is gently inserted into the rectum. The prostate is palpated, and any nodules, indurations or asymmetry should be noted. Although the seminal vesicle is too far to reach in most men, they may occasionally be palpable just above the prostate. Having the patient Valsalva will often bring the prostate closer to the anus and facilitate the exam.

LABORATORY EXAMINATION Examination of the Urine In the patient with urologic complaints, urinalysis is a simple, but powerful tool. The proper collection of the urine sample is critical. Ideally, the urine sample is collected by sterilely catheterizing the bladder. However, this is not always practical, and a clean midstream catch is usually adequate, especially in men. In women, an abnormal urinalysis may need to be confirmed with a catheterized specimen to rule out possible contamination by the vaginal flora. In children, urine can be collected by placing a urine collection bag over the urethral meatus; however, urine specimen for bacterial culture may need to be obtained by catheterization or suprapubic aspiration. The complete urinalysis includes testing with a dipstick impregnated with an array of chemical reagents and a microscopic examination of urinary sediments obtained by centrifugation.1,2 A reasonable approach to urinalysis is to reserve the microscopic examination for patients with abnormalities detected using the dipstick. Most standard dipsticks will test for urinary pH, specific gravity, protein, glucose, ketones, bilirubin, urobilinogen, hemoglobin, leukocytes, and nitrites. The dipstick analysis relies on color changes produced by chemical reactions with substances in the urine, and, therefore, any medications taken by the patient that changes the color of the urine, such as phenazopyridine (Pyridium), will interfere

39/UROLOGY

with the test. Usually the urine pH will reflect the pH of the serum. Exceptions to this rule occur in patients with renal tubular acidosis or a urinary tract infection involving a urea-splitting organism. The specific gravity of the urine reflects the hydration status of the patient and the concentrating ability of the kidney. Proteinuria detected on dipstick may indicate intrinsic renal pathology or the presence of excess protein in the serum. Persistent proteinuria determined using a dipstick should be confirmed by a 24-hour urine collection for protein. Testing for urinary glucose and ketones is useful in screening for diabetes. Urinary glucose will usually be detected when serum glucose levels are greater than 180 mg/dL. A small amount of urobilinogen can normally be detected in the urine. However, a positive test for bilirubin and high levels of urobilinogen may indicate liver disease or hemolysis. Presence of hemoglobin, myoglobin, and red blood cells in the urine can produce a positive result on dipstick tests for blood. Therefore, a positive dipstick test should be confirmed by microscopy. A positive urinalysis for leukocytes and nitrites suggests inflammation, which is most commonly caused by a bacterial infection. The dipstick tests for leukocyte esterase, which is an enzyme found in neutrophils. The urine may be positive for leukocytes in the presence of both hematuria and pyuria. Therefore, suspected pyuria should be confirmed by microscopic examination of the urine. Normal urine does not contain nitrites. However, in the presence of urea-splitting organisms, urinary nitrates are converted to nitrites, which can be detected by the dipstick test. Urea-splitting bacteria include the Proteus, Klebsiella, Pseudomonas, Enterococcus, and Morganella species. This list does not include Escherichia, which is the most common cause of urinary infections.

Urine Culture It is important to keep in mind that the urinalysis results may be normal in patients with a urinary tract infection. A urine culture is the most definitive test for symptomatic patients. Greater than 105 organisms/mL of urine is consistent with a urinary tract infection. However, in patients who have irritative voiding symptoms, such as frequency and dysuria, 100 organisms/mL of a known urinary pathogen is sufficient evidence of a bacterial infection. In patients with recurrent or resistant infections, it may be important to identify the organism and test for antibiotic sensitivities by using a urine culture. Some urinary pathogens, such as Neisseriae, Mycobacteria, and anaerobes, require special culture techniques and a local laboratory should be consulted regarding the specific requirements.

Tests of Kidney Function Several simple tests can be used to estimate kidney function. Urinespecific gravity can be measured in the office by using a dipstick. As renal function decreases, the ability of the kidney to concentrate urine decreases. This is reflected by a proportional change in specific gravity. However, specific gravity is also dependent on hydration status, and with a progressive decrease in renal function, the specific gravity does not decrease below approximately 1.015. Serum creatinine level is a better approximation of kidney function. Creatinine is an end-product of muscle creatine metabolism and is excreted by the kidney. Serum creatinine levels are less affected by hydration status. However, creatinine does not reflect early loss of renal function, as serum creatinine levels remain in the normal range until approximately 50% of the kidney function is lost.

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The best measure of kidney function that does not involve infusion of exogenous substances is the endogenous creatinine clearance rate. Creatinine clearance is defined as the volume of plasma from which creatinine is completely removed per unit of time and is a clinical approximation of the glomerular filtration rate (GFR) and renal function. Creatinine clearance is calculated from a 24-hour urine collection according to the following formula: Clearance = UV/P In this formula, U and P represent the urine and plasma concentrations of creatinine, respectively, and V represents the urine flow rate. Normal creatinine clearance is 90 to 110 mL/min. The gold standard for measuring GFR involves infusing and measuring the clearance of inulin. Inulin is an ideal substance for measuring GFR because it is completely filtered by the kidney without being secreted or reabsorbed by the tubules. In contrast, creatinine is secreted in small amounts by the proximal tubule. Therefore, creatinine clearance will slightly overestimate GFR at all levels of kidney function. This effect is most pronounced when kidney function is severely compromised, where creatinine clearance can overestimate GFR by as much as 1.5- to twofold.

RADIOLOGIC STUDIES OF THE URINARY SYSTEM Imaging of Kidney and Ureter With recent improvements in computed tomography (CT) technology, CT scans have become the study of choice for general imaging of the kidney and ureter.1,2 The primary advantage of a CT scan is the amount of information it provides. On a CT scan, kidney stones that are radiolucent on plain x-ray are readily visible (Fig. 39-7). Uptake of contrast by the renal parenchyma during the nephrogram phase of the CT scan provides a rough estimate of the kidney function. A comparison of the uptake of contrast by each kidney provides an estimate of the differential function between the right and left kidneys. After the contrast is excreted by the kidney into the collecting system, the collecting system can be evaluated for subtle filling defects and hydronephrosis. The CT scan also allows for evaluation of other organ systems in the abdomen and pelvis. CT scans are useful when renal or ureteral malignancy is suspected. When a CT scan is performed for evaluation of hematuria, the study should be performed with and without IV contrast, and delayed images should be obtained after the contrast has been excreted into the renal pelvis and ureter. Renal cell carcinomas classically appear as solid, enhancing masses. The degree of enhancement can be determined by comparing the images with and without contrast. Transitional cell tumors of the renal pelvis and ureter often present as filling defects on delayed images. Transitional cell tumors in the kidney and ureter can obstruct the collecting system and hydronephrosis may be seen. When a CT scan is performed for evaluation of malignancy, oral contrast should be given. This will facilitate delineation of any pathologically enlarged lymph nodes in the retroperitoneum and pelvis. Although CT scan is the study of choice in most settings, an intravenous pyelogram (IVP) is a better test when the primary goal is to evaluate the collecting system. To obtain an IVP, radiologic contrast is infused and a series of plain x-rays are taken of the abdomen and pelvis. The diameter and contour of the renal pelvis is readily appreciated on IVP, and congenital anomalies of the ureter and renal pelvic filing defects are easily seen. When an IVP is not

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A

B

diagnostic, or if the patient is allergic to IV contrast, a retrograde pyelogram can be performed (Fig. 39-8). A magnetic resonance image (MRI) obtained with contrast medium such as gadolinium can generally be used in place of a CT scan when renal insufficiency or contrast allergy prohibits the use of CT contrast.

FIG. 39-7. ( A ) CT scan performed without IV contrast and ( B ) CT scan performed with IV contrast. A urinary stone is visible at the level of the (right) ureteropelvic junction, causing hydronephrosis. Following administration of contrast, there is a delay in uptake of contrast by the right kidney, suggesting a decrease in renal function. The right renal function is expected to return to normal after relief of urinary obstruction of limited duration.

A retrograde pyelogram is performed by visualizing the ureteral orifice through a cystoscope and cannulating the ureters with a 6 to 8 F catheter. Radiologic contrast is injected through the catheter and the collecting system is visualized in real-time by fluoroscopy. At the time of the procedure, a urine sample or a saline

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FIG. 39-8. Retrograde pyelogram. A filling defect, suspicious for a transitional cell carcinoma, is present in the left renal pelvis (arrow).

wash sample from the upper tract can be collected through the ureteral catheter and sent for cytology or culture. Urine collected from each of the upper tracts may allow for localization of malignancy or infection to the right or left side. The primary disadvantage to performing a retrograde pyelogram is that it is an invasive procedure, which is usually performed in the operating room under anesthesia. The least-invasive imaging modality for the kidney is a renal ultrasound. Many common renal pathologies have a characteristic appearance on ultrasound. Kidney stones are identified as a hyperechoic lesion associated with hypoechoic “shadowing” behind the stone (Fig. 39-9). On ultrasound, fluid is hypoechoic, therefore renal cysts and hydronephrosis are readily identified. Renal masses appear as hyperechoic lesions and generally warrant further evaluation with a CT scan. In the pediatric population, a renal ultrasound is the first screening test obtained when a congenital abnormality of the urinary system is suspected.

The patient is then asked to void the contrast and a urethrogram is taken. In the pediatric population, a VCUG is most commonly performed to rule out ureteral reflux or a posterior urethral valve. In adults, a cystogram is most commonly performed to rule out a bladder perforation in a trauma patient.

Imaging of the Bladder and Urethra A urethrogram should be performed when a urethral stricture or a traumatic urethral disruption is suspected (Fig. 39-10). A Foley catheter is inserted just beyond the tip of the meatus and the catheter balloon is inflated with approximately 0.5 mL of fluid. Radiologic contrast is injected in a retrograde fashion and a plain x-ray is taken. Alternatively, the urethra is visualized during the injection using fluoroscopy. An antegrade urethrogram can also be performed during a voiding cystourethrogram (VCUG). For a VCUG, a small-diameter catheter is inserted into the bladder and a cystogram is obtained.

FIG. 39-9. Renal ultrasound demonstrating a urinary stone. The urinary stone is a hyperechoic lesion creating a hypoechoic “shadow” distally.

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estimating differential renal function, and evaluating drainage of the renal pelvis.

BENIGN PROSTATIC HYPERPLASIA Etiology BPH refers to the stromal and epithelial proliferation in the prostate gland that may eventually result in voiding symptoms. BPH occurs primarily in the transition zone of the prostate gland (see Fig. 393). In autopsy studies, histologic evidence of BPH is rare in men who are younger than 40 years of age; however, it can be found in approximately 70% of men in their seventies, and in nearly all men in their nineties.4 Although androgen production is required for BPH to occur, androgen merely plays a permissive role in the development of BPH. The precise hormonal, autocrine, and paracrine factors involved in stimulating BPH are unknown.

Natural History

FIG. 39-10. Retrograde urethrogram. The urethrogram obtained following blunt trauma to the pelvis demonstrates a urethra disruption where extravasation of radiologic contrast is seen.

Testicular Ultrasound A testicular ultrasound is most commonly performed to evaluate testicular pain or a palpable lesion noted on physical examination. The differential diagnoses for acute testicular pain include testicular torsion, epididymal orchitis, and scrotal abscess. On Doppler ultrasound, the absence of blood flow is consistent with a testicular torsion, while increased blood flow suggests epididymal orchitis. For palpable lesions of the testicle, an ultrasound is well suited for distinguishing between solid and cystic lesions. Solid masses in the testicle or in the epididymis should be considered a malignancy until proven otherwise and an orchiectomy should be performed to make a definitive diagnosis.

Renal Scan A renal scan is a nuclear medicine study used to determine renal function and evaluate drainage of the renal pelvis and ureter (Fig. 39-11). After intravenous administration of a radioactive tracer, the kidneys are imaged. Depending on the indications for the study, different tracers are used. If the primary purpose of the study is to image the renal cortex to detect parenchyma scarring, which is often seen in pediatric patients following an episode of pyelonephritis, technetium-99m dimercaptosuccinic acid (DMSA) is used. This tracer is bound to the proximal tubule and is slowly excreted, a property that makes it an ideal agent for visualizing the kidney cortex. Technetium-99m diethylenetriamine-pentaacetic acid (DTPA) is excreted following glomerular filtration and can be used to determine the GFR DTPA also can be used to evaluate the drainage of the collecting system. Once DTPA is excreted into the renal pelvis, Lasix can be given and the half-life (T1/2 ) of the tracer activity is measured. A high T1/2 (greater than 20 minutes) is consistent with an obstruction. The third agent, technetium-99m mercaptoacetyltriglycine (MAG-3), is both filtered by the glomeruli and secreted by the tubules. Therefore, it is well suited for imaging the renal cortex,

Patients with BPH can present with both obstructive and irritative voiding symptoms, which are often referred to collectively as lower urinary tract symptoms (LUTS). Patients may complain of a decreased urinary stream, frequency, nocturia, urgency, hesitancy, intermittency, and a sense of incomplete emptying. Although these symptoms are certainly related to a bladder outlet obstruction secondary to an enlarged prostate, other, less-clearly defined factors are involved. This is underscored by several studies documenting that there is a minimal relationship between the degree of symptoms, the size of the prostate, and the degree of urethral obstruction.5,6 Therefore, treatment should primarily be dictated by the patient’s symptoms and the extent to which the patient is bothered by the symptoms, rather than merely the size of the prostate gland. Without treatment, the symptoms of BPH tend to wax and wane over the short-term; however, with long-term follow-up, the common trend is toward a worsening of symptoms. As the transition zone of the prostate enlarges and becomes progressively more obstructive, the bladder initially undergoes compensatory hypertrophy. As long as the hypertrophied bladder is able to generate enough pressure to overcome the increased outlet resistance, the patient is able to void to completion. However, as the bladder outlet resistance continues to increase, the bladder may not be able to generate enough pressure to overcome the outlet resistance. Persistent bladder outlet obstruction and increasing postvoid urinary residuals lead to a decompensated bladder characterized by a thin bladder wall, large capacity, and poor contractility. Without intervention, potential sequelae of a decompensated bladder include urinary retention requiring emergent catheterization, upper tract dilation, and renal failure. The differential diagnosis for a patient presenting with LUTS includes urinary tract infection, prostatitis, bladder stones, urethral stricture, and neurogenic bladder. The work-up for LUTS should include a thorough voiding history. The symptoms can be quantified by having the patient fill out an international prostate symptom score (I-PSS) questionnaire (Table 39-1). This questionnaire has been validated as a useful means for assessing and following symptoms resulting from BPH.7 Treatment is recommended for an I-PSS greater than 7. A digital rectal exam and a focused neurologic exam should be performed because symptoms such as urgency and frequency may be signs of a neurologic disorder.8 A urinalysis should be obtained in all patients and a urine culture should be obtained in patients with dysuria or abnormal urinalysis.

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A

FIG. 39-11. A . Renal scan in a patient with a ureteropelvic junction obstruction. Renal scan obtained using technetium-99m mercaptoacetyltriglycine (MAG-3). A quantitative assessment of uptake of MAG-3 by the renal parenchyma approximately 2 minutes following injection suggests that the differential functions of the left and right kidneys are 52 and 48%, respectively. B . Following administration of Lasix, the T1/2 for the washout of the nucleotide in the renal pelvis of the right kidney is 9 minutes and 30 seconds; however, the nucleotide never washes out of the left kidney. T1/2 >20 minutes is consistent with obstruction.

B

In patients presenting with urinary retention or severe voiding symptoms, a check of serum creatinine levels to evaluate renal function is reasonable. Other studies can be more selectively obtained in patients with voiding symptoms. Cystoscopy should be performed for patients who also present with hematuria or when a urethral stricture is suspected. For patients with a very poor stream, or for patients complaining of a sense of incomplete emptying, a postvoid residual should be measured by ultrasound or by catheterization. A renal ultrasound should be performed in patients with an elevated creatinine. For select patients, a pressure-flow study may be necessary. A decrease in urinary flow may result from bladder outlet obstruction or from failure of the bladder to effectively contract. To distinguish between the two, a small-diameter catheter can be inserted into the bladder to transduce bladder pressures during voiding. High bladder pressure and low flow rates are consistent with obstruction. Low bladder pressure and low flow rates suggest a neurogenic bladder that is unable to effectively contract.

Medical Therapy BPH is not always progressive. Patients with mild symptoms can be managed by watchful waiting. Patients with more severe symptoms should be treated based on the degree of bother. Absolute indications for treatment include urinary retention, bladder stones, upper tract dilation, and renal failure. Relative indications for treatment include large postvoid residuals, hematuria, and recurrent urinary tract infections. There are two components to the bladder outlet obstruction resulting from BPH: mechanical and dynamic. The mechanical

component refers to the urethral compression resulting from the enlarged prostate. The dynamic component refers to the smooth muscles in the urethra and prostatic stroma that contract and further obstruct the bladder outlet.9 The smooth muscles at the bladder outlet are under alpha1 adrenergic innervation. The first line therapy for BPH is an alpha blocker, which targets the dynamic component of the bladder outlet obstruction. Three alpha blockers that are available in the United States for the treatment of BPH are terazosin, doxazosin, and tamsulosin.10 Terazosin and doxazosin are selective for alpha1 adrenoceptors, which are found in the prostate, as well as in the vascular endothelium and central nervous system. Both terazosin and doxazosin significantly lower blood pressure, especially in men with clinical hypertension. Therefore, terazosin and doxazosin are good choices in the approximately 30% of men with BPH who also have clinical hypertension. The most common side effects with these two medications are dizziness and orthostatic hypertension. Both medications should be titrated up over 1 to 2 weeks to their target dose. Tamsulosin is the newest alpha blocker. It is selective for the α1a -adrenoceptor subtype, which is predominately found in the prostate.11 Its effect on blood pressure is clinically insignificant, and its primary advantage is that it does not need to be titrated. It can be started at its effective dose. Retrograde ejaculation, which refers to the passage of semen into the bladder during ejaculation, and rhinitis are more common with tamsulosin than with the less specific alpha1 blockers. Although the side-effect profiles differ slightly between the alpha blockers, all three alpha blockers appear to be equally effective for the treatment of BPH.

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Table 39-1 International Prostate Symptom Score (I-PSS) Questionnaire

1. Incomplete Emptying Over the last month, how often have you had a sensation of not emptying your bladder completely after you finish urinating? 2. Frequency Over the last month, how often have you had to urinate again less than two hours after you finished urinating? 3. Intermittency Over the last month, how often have you found you stopped and started again several times when you urinated? 4. Urgency Over the last month, how often have you found it difficult to postpone urination? 5. Weak Stream Over the last month, how often have you had a weak urinary stream? 6. Straining Over the last month, how often have you had to push or strain to begin urination?

7. Nocturia Over the last month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?

Not At All

Under 1/5 the Time

Under 1/2 the Time

1/2 Time

Over 1/2 the Time

Almost Always

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

0

1

2

3

4

5

None

1 Time

2 Times

3 Times

4 Times

5+ Times

0

1

2

3

4

5

Delighted

Pleased

Mostly Satisfied

Mixed

Mostly Dissatisfied

Unhappy

Terrible

0

1

2

3

4

5

6

Your Score

Your Score

Total I-PSS Score

Quality of Life Due to Urinary Symptoms If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?

Patients in urinary retention require emergent catheterization and the catheter should be left in place for at least 24 hours to allow the acutely distended bladder to remain decompressed. Tamsulosin may be preferred for previously untreated patients who present in acute urinary retention. Before attempting catheter removal, tamsulosin can be started at the therapeutic dose without need for titration. Other common medical therapies for BPH include saw palmetto and finasteride.12,13 Saw palmetto is derived from the American dwarf palm tree and is sold in the United States as an herbal supplement. In several randomized, controlled studies, saw palmetto improved symptoms and urinary flow rates. Multiple studies have shown that saw palmetto is safe with no significant adverse effects; however, the precise mechanism of action is not known. Finasteride is commonly used for the treatment of BPH as well as for the treatment of hair loss. Development of prostatic hyperplasia requires the presence of androgen, and more specifically, dihydrotestosterone. Finasteride is a 5α-reductase inhibitor, and it blocks the conversion of testosterone to dihydrotestosterone. Finasteride is effective in decreasing the risk of urinary retention and hematuria

Your Score

in men with very large prostate glands. However, finasteride has no proven benefit in men with LUTS and smaller prostate glands.

Surgical Management Surgery should be recommended for patients who continue to be bothered by their symptoms or who experience urinary retention despite medical therapy. Surgery should also be recommended for patients with upper tract dilation, renal insufficiency secondary to BPH, or bladder stones. Surgery for BPH is most commonly performed endoscopically; however, if the prostate gland is greater than 80 to 100 g, an open prostatectomy should be performed. The standard endoscopic procedure for BPH is a transurethral resection (TUR) of the prostate. TUR is performed with a nonhemolytic fluid such as 1.5% glycine. Saline cannot be used because electrolytes in the irrigation fluid will dissipate the electric current used to resect the prostate. During the resection some of the irrigation fluid is absorbed through venous channels in the prostate. If enough fluid is absorbed, TUR syndrome may develop from the resulting hypervolemia and dilutional hyponatremia. Patients with TUR syndrome may experience hypertension, bradycardia, nausea, vomiting, visual disturbance, mental status changes, and even seizures. During

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the procedure and the postoperative period, patients should be monitored for evidence of TUR syndrome, which occurs in approximately 2% of patients. Patients with evidence of TUR syndrome should be treated with diuretics, and electrolyte imbalances should be corrected. Following a TUR, patients are hospitalized overnight for continuous bladder irrigation. The hematuria is usually minimal by the following day, and the bladder irrigation can be stopped. If the urine remains clear or light pink while off irrigation, the catheter can be removed and the patient discharged from the hospital. Although TURs are associated with minimal morbidity, bleeding can occasionally be significant. In an attempt to further minimize the morbidity of BPH surgery, other technologies for ablating the prostate have been advocated. These newer technologies use lasers or produce thermal ablation by using radiofrequency or microwave energy.14 Most studies have concluded that while these newer options are slightly less morbid than a TUR, they are also less effective than TUR in relieving the BPH-related obstruction.

UROLOGIC ONCOLOGY Renal Cell Carcinoma Epidemiology Each year more than 30,000 new cases of renal cell carcinoma are diagnosed in the United States, resulting in approximately 12,000 deaths.15 With the increased use of ultrasonography and CT scanning, incidental detection of early renal cell carcinoma has accounted, at least in part, for a 3% increase in incidence each year since the 1970s.16 However, the mortality rate for renal cell carcinoma also has been increasing, suggesting that other factors are involved. Currently, renal cell carcinoma represents approximately 3% of all malignancies. The male:female ratio is approximately 3:2. At the time of diagnosis, approximately one-third of patients have metastatic disease.

Presentation and Prognosis

FIG. 39-12. CT scan with IV contrast demonstrating an enhancing, solid mass of the left kidney.

as a CT scan, MRI, or renal ultrasound. A solid, enhancing mass in the kidney has a 90% chance of being a renal cell carcinoma (Fig. 39-12). Except in select cases, a renal biopsy is unnecessary. A renal biopsy is associated with a high false-negative rate because of potential sampling error and difficulty interpreting the pathology from a biopsy sample. Therefore, a negative or nondiagnostic biopsy does not obviate the need for surgical removal of the mass. A biopsy may be helpful in patients with a history of another primary malignancy or in patients with metastatic disease in whom the primary site is unknown. In these patients, a biopsy is performed to determine whether the renal mass is a primary tumor or a metastatic deposit. A simple cyst in the kidney is a common, benign finding. However, a complex cyst may harbor a malignant tumor (Fig. 39-13). Several features of a renal cyst are suggestive of a malignant

Before the widespread use of radiologic studies, patients often presented with advance disease with findings of a palpable mass, flank pain, and hematuria. Today, most renal tumors are incidentally discovered on ultrasounds and CT scans performed for unrelated disorders.17 Patients with renal cell carcinoma also can present with paraneoplastic manifestations such as anemia, hepatic dysfunction (Stauffer syndrome), cachexia, polycythemia, and hypercalcemia. Paraneoplastic findings result from soluble substances released by the tumor or by immune cells in response to the tumor. Paraneoplastic findings resulting from localized disease resolve following a nephrectomy. Well-established predictors of prognosis include stage, grade, and performance status. Renal cell carcinomas can be staged according to the tumor–node–metastasis (TNM) staging criteria proposed by the American Joint Committee on Cancer. Tumor grade is determined by using the Fuhrman grading system, which categorizes nuclear grade. Performance status is determined by the patient’s ability to provide self-care and perform normal, day-to-day activities. Other reported indicators of poor prognosis include cachexia, anemia, hypercalcemia, and sarcomatoid histologic features.

Work-Up All patients with a history of gross or microscopic hematuria should undergo a cystoscopy and an upper tract imaging study such

FIG. 39-13. CT scan with IV contrast demonstrating a complex left renal cyst. A complex cyst may harbor a malignancy. Features of a renal cyst suggestive of a malignant component include multiple septations, irregular cyst walls, calcifications, and walls or septations that enhance with IV contrast on CT scan.

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Treatment

FIG. 39-14. CT scan demonstrating an angiomyolipoma of the right kidney. The fatty component has a characteristic dark appearance on CT scan. Angiomyolipomas can usually be diagnosed by radiologic criteria alone and a histologic diagnosis is not necessary.

component. These features include multiple septations, irregular cyst wall, calcifications, and wall or septations that enhance with IV contrast on CT or MRI. The most common benign tumors in the kidney are oncocytomas and angiomyolipomas. Oncocytomas do not have a characteristic radiologic appearance and the diagnosis is made histologically following a nephrectomy. Angiomyolipomas are benign lesions common in patients with tuberous sclerosis. They have a characteristic appearance on CT scan, and nephrectomy is generally not necessary to confirm the diagnosis (Fig. 39-14). Large angiomyolipomas, however, have a high risk of bleeding and embolization should be considered for lesions larger than 4 cm. Several histologic subtypes of renal cell carcinoma have been defined. Approximately 80% of renal cell carcinomas are clear cell tumors and approximately 75% of sporadic clear cell tumors have a mutation of the von Hippel-Lindau (VHL) gene found on chromosome 3.18 The papillary subtype represents 10 to 15% of renal cell carcinomas and is associated with activation of the MET protooncogene or cytogenetic abnormalities involving chromosomes 7 and 17.19 Both clear cell and papillary subtypes are thought to arise from the proximal tubules of the nephron. Chromophobe and collecting duct subtypes represent most of the remaining renal cell carcinomas and both are thought to arise from the distal tubules and collecting duct of the nephron. Stage for stage, there is no consensus on the prognostic significance of these four subtypes. However, medullary cell carcinoma is a rare subtype that occurs in younger patients with sickle cell trait and is uniformly associated with a poor prognosis. Sarcomatoid lesions in a tumor also suggest a poor prognosis; however, this lesion is not considered a separate subtype. All patients with a renal mass should undergo a metastatic workup that includes liver function tests, chest x-ray, and imaging of the abdomen and pelvis with a CT scan or MRI. The CT scan or MRI should be performed with and without IV contrast. If there is any suspicion of renal vein or inferior vena cava involvement by a tumor thrombus, a vena cavagram or MR angiogram with coronal sections should be performed to evaluate the extent of caval involvement. Patients with metastatic lesions on imaging of the chest, abdomen, and pelvis should undergo a bone scan and a head CT as well.

The standard treatment for localized renal cell carcinoma remains a radical nephrectomy. The classic radical nephrectomy involves removal of the kidney, the ipsilateral adrenal gland, and all the fat contained within Gerota’s fascia. However, it has been shown that if there is no evidence of adrenal involvement by the tumor on the CT scan, the adrenal gland can be spared. A radical nephrectomy can be performed using either an open or a laparoscopic approach. The laparoscopic approach is associated with less postoperative pain and a more rapid return to normal activities. For a radical nephrectomy, a laparoscopic procedure is now the standard of care. For tumors less than 4 cm in size, a partial nephrectomy is an equally effective option for cancer control.20 It is preferred in patients who are at risk for renal insufficiency secondary to conditions such as hypertension, recurrent stone disease, or diabetes. When performing a partial nephrectomy, meticulous attention needs to be paid to preventing bleeding and urine leaks, and this is most effectively accomplished by an open surgical approach (Fig. 39-15). Although laparoscopic partial nephrectomies have been reported, an open surgical procedure remains the standard of care when performing a partial nephrectomy. Another option for a small renal lesion (less than 3 cm in diameter) is laparoscopic cryoablation.21 The tumor is mobilized laparoscopically and cryoprobes that deliver argon gas or liquid nitrogen are inserted into the tumor. Usually a double freeze–thaw cycle is used to ablate the tumor. Although follow-up is limited, early reports suggest that cryotherapy is an effective treatment for small, peripheral lesions. Metastatic renal cell carcinoma is resistant to radiation and standard chemotherapies. There are several important principles to guide the treatment of metastatic disease. Any metastatic lesion to the central nervous system can become rapidly symptomatic and should be addressed by the radiation oncologist and neurosurgeon prior to initiating any further treatment. Patients with a relatively good prognosis, as determined by a good performance status and a limited number of metastatic sites, are candidates for a cytoreductive nephrectomy and interleukin-2 or interferon-based immunotherapy. The combination of neoadjuvant nephrectomy and immunotherapy represents the current standard of care for patients with metastatic renal cell carcinoma.22,23 Approximately 75% of patients treated for localized renal cell carcinoma are cured of their disease. For patients with metastatic disease, the response rates for treatment with immunotherapy range from 10 to 20% and the median survival is 12 to 17 months.24,25 However, it is important to point out that with immunotherapy durable responses lasting as long as 10 years are achieved in approximately 5 to 7% of patients.

Bladder Cancer Epidemiology In the United States, approximately 56,000 new cases of bladder cancer are diagnosed each year, resulting in approximately 13,000 deaths.15,26,27 Bladder cancer represents 7% of all newly diagnosed cancers in men and 2% of all newly diagnosed cancers in women. Following prostate cancer, it is the most common genitourinary cancer in men. Bladder cancer is approximately 2.5 times more common in men than in women, and is more common in whites than in African American and Hispanic populations. The median age at diagnosis is 68 years and the incidence increases directly with

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FIG. 39-15. Partial nephrectomy. A . The patient is placed in a flank position. B . The kidney should be cooled with ice before clamping the artery with a bulldog clamp. C . The tumor is sharply excised with a margin of normal tissue. D . The collecting system is identified and divided if necessary. E . The collecting system and bleeding vessels are meticulously oversewn with absorbable sutures. F . The capsule is closed and covered with fat.

age. The majority of patients with bladder cancer have superficial disease, which is associated with long-term survival. Therefore, there is a cohort of 300,000 to 400,000 patients with bladder cancer in the United States at all times. In Western countries, more than 90% of bladder cancers are transitional cell carcinomas, approximately 5% are squamous cell carcinomas, and less than 2% are adenocarcinomas. In the developing countries, 75% of bladder cancers are squamous cell carcinomas and most of these are secondary to Schistosoma haematobium infection. Squamous cell carcinomas of the bladder in the United States are associated with chronic inflammation caused by chronic indwelling Foley catheters and bladder stones. There is no convincing evidence for a hereditary factor in the development of bladder cancer. Although most of the following discussion applies to bladder cancer in general, the primary focus is on transitional cell carcinoma (TCCa). TCCa is strongly linked to environmental exposures. Smoking accounts for more than 50% of bladder cancers, and 2naphthylamine and 4-aminobiphenyl are likely the most significant carcinogens found in cigarette smoke that lead to TCCa. The development of bladder cancer also has been associated with industrial exposure to aromatic amines in dyes, paints, solvents, leather dust, inks, combustion products, rubber, and textile. Prior radiation treatments to the pelvis and acrolein, a urinary metabolite of

cyclophosphamide, increase the risk of bladder cancer. However, coffee and artificial sweeteners are not believed to increase the risk of bladder cancer in humans.

Presentation The classic presentation of bladder cancer is painless hematuria. Eighty-five percent of patients with bladder cancer present with hematuria.28 Hematuria, whether gross or microscopic, requires a urologic evaluation. Microscopic hematuria as a result of bladder cancer may be intermittent, therefore, bladder cancer cannot be ruled out with a repeat negative urinalysis. Persistent, irritative voiding symptoms may be a result of carcinoma in situ (CIS) or muscleinvasive bladder cancer. Therefore, irritative voiding symptoms that do not resolve with treatment for a urinary tract infection require further evaluation. A urologic work-up for hematuria includes cystoscopy and radiographic imaging of the upper urinary tract as previously discussed.

Work-Up At the time of clinic cystoscopy, a bladder wash for cytology can be sent. Bladder cytology is 95% accurate for diagnosing highgrade tumors and CIS, however, its accuracy for diagnosing lowgrade carcinoma is only 10 to 50%. Newer assays for the detection and surveillance of TCCa in voided urine include the BTA-Stat,

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Ta

Cis

Peritoneum Muscularis propria Lamina propria Mucosa

T1 T2a T2b T3a T3b T4

Perivesical fat

FIG. 39-16. Cystoscopic image of a papillary bladder lesion suspicious for a transitional cell carcinoma.

NMP-22, and FDP tests.29 However, because of high false-positive rates and high false-negative rates, it is unlikely that these tests will obviate the need for cystoscopy. Patients with an abnormal cystoscopic exam or suspicious bladder wash cytology should be further evaluated with an operating room cystoscopy (Fig. 39-16). In the operating room, all suspicious lesions should be endoscopically biopsied. Blood effluxing from either ureteral orifice should be further investigated with a retrograde pyelogram and possibly ureteroscopy. Both tumor grade and stage correlate independently with prognosis. Transitional cell cancer is most commonly graded on a scale between 1 and 3, representing well, moderate, and poorly differentiated tumors. The TNM system, developed by the International Union Against Cancer and the American Joint Committee on Cancer Staging, is used to stage bladder cancer (Fig. 39-17). Tumors that involve the bladder mucosa (Ta and CIS) or lamina propria (T1) are considered superficial cancers. CIS is a unique designation that signifies a flat, high-grade tumor confined to the mucosa, and CIS generally implies a higher risk of recurrence following treatment. Tumors that invade the muscular layer of the bladder wall (T2) or beyond (T3 and T4) are considered muscle invasive. Approximately 25% of patients with bladder cancer have muscle-invasive disease at the time of diagnosis.28 Patients with muscle-invasive bladder cancer should undergo a metastatic workup, which includes a CT scan of the abdomen and pelvis, chest x-ray, serum chemistries, and liver function tests. If the patients are asymptomatic with normal calcium and alkaline phosphatase, bone scans are unnecessary. Approximately 15% of all patients have metastatic disease at the time of initial presentation.30 The life expectancy for most patients with overt metastatic disease is less than 2 years; however, approximately 25% of patients with only limited regional lymph node metastases discovered during cystectomy and pelvic lymph node dissection may survive beyond 5 years.31,32

Treatment of Superficial Bladder Cancer (Ta, T1, CIS) Most superficial bladder cancers are adequately treated by endoscopic resection and fulguration of the bladder tumor. No further

FIG. 39-17. Staging of bladder cancer. T stage determined by depth of invasions: Cis = carcinoma in situ; Ta = mucosa; T1 = lamina propria; T2a = superficial bladder muscle; T2b = deep bladder muscle; T3a = perivesical fat (microscopic); T3b = perivesical fat (gross); T4 = adjacent structures such as prostate, rectum, or pelvic sidewall.

metastatic work-up is indicated if the pathology confirms a lowgrade, superficial TCCa. However, bladder cancer is considered a polyclonal, field-change defect and continued surveillance is mandatory. In other words, the underlying genetic changes that resulted in the bladder cancer have occurred in the entire urothelium, making the entire urothelium susceptible to future tumor formation. The risk of recurrence following the treatment of superficial bladder cancer is approximately 70% within 5 years.33 The risk of disease progression, defined as a subsequent increase in tumor grade or stage, depends on the initial tumor grade. The risk of progression for TCCa grades I, II, and III is 10 to 20%, 19 to 37%, and 33 to 67%, respectively.34 Carcinoma in situ alone or in association with Ta or T1 papillary tumor carries a poorer prognosis, with a recurrence rate of 63 to 92%. Other risk factors for recurrence and progression include tumor size, grade, and interval to recurrence. The high rate of disease recurrence and progression in superficial bladder cancer underscores the need for careful follow-up. Patients with a history of superficial TCCa should undergo surveillance with cystoscopy and bladder wash cytology every 3 months for 2 years. If they are disease free during this period, the follow-up intervals can be gradually increased. Intravesical therapy is effective for patients with high-risk, superficial TCCa in reducing the risk of recurrence.35 The most effective intravesical therapy is bacille Calmette-Gu´erin (BCG), which is a live, attenuated strain of Mycobacterium bovis. BCG is recommended for carcinoma in situ, T1 tumors, and high-risk Ta tumors (large, high-grade, recurrent or multifocal tumors). The beneficial effects of intravesical BCG is thought to be mediated by a nonspecific immune cytokine response. Because BCG is a live, attenuated organism, it can cause tuberculosis-like symptoms if it is absorbed into the bloodstream. Contraindications for BCG treatment include active hematuria, immunodeficiency, and active urinary tract

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infection. BCG therapy reduces recurrence and some studies suggest it may reduce the risk of progression as well. Other forms of adjuvant therapy for superficial bladder cancer include intravesical triethylenethiophosphoramide (thiotepa), mitomycin C, doxorubicin, and epirubicin. Although these agents can increase the time to disease recurrence, there is no evidence that any of these intravesical chemotherapies can prevent disease progression. With treatment, superficial bladder cancer has a good prognosis with 5-year survival rates of 82 to 100%.

Treatment of Muscle-Invasive Bladder Cancer (T2, T3, T4) The gold standard for organ-confined, muscle-invasive bladder cancer (T2 and T3) is radical cystoprostatectomy in men and anterior pelvic exenteration in women. In men, radical cystectomy involves the removal of the bladder, prostate, and pelvic lymph nodes. A total urethrectomy also is performed if the urethral margin is positive. In women, a classic anterior pelvic exenteration includes the removal of the bladder, urethra, uterus, ovaries, and anterior vaginal wall. However, in a female patient, if the bladder neck margin is negative, the urethra and anterior vaginal wall may be spared. With treatment, the 5-year survival rates for pathologic T2, T3, T4a, and N+ tumors are 63 to 80%, 19 to 57%, 0 to 36%, and 15 to 44% respectively.36 After cystectomy, the urine is diverted using segments of bowel. The various types of urinary diversions can be separated into continent and incontinent diversions. The most commonly performed incontinent diversion is the ileal conduit. A small segment of ileum is taken out of continuity with the GI tract while maintaining its mesenteric blood supply. The ureters are anastomosed to one end of the conduit and the other end is brought out to the abdominal wall as a stoma. The urine continuously collects in an external collection device worn over the stoma. There are two commonly performed continent urinary diversions. An Indiana pouch is a urinary reservoir created from detubularized right colon and an adjacent limb of terminal ileum (Fig. 39-18). The terminal ileum is plicated and brought to the abdominal wall, creating a catheterizable stoma. The native ileocecal valve provides the continence mechanism. The Indiana pouch is emptied by clean intermittent catheterization of the stoma four to six times per day. An orthotopic neobladder is a similar reservoir that is connected to the urethra (Fig. 39-19). Various segments of intestine, including small and large bowel, may be used in constructing the orthotopic neobladder. The orthotopic neobladder most closely restores the natural storage and voiding function of the native bladder. Patients have volitional control of urination and void by Valsalva maneuver. In certain centers, a bladder preserving strategy for T2-T3 TCCa is applied using a combination of external beam radiation, chemotherapy and endoscopic resection.37 This approach has resulted in comparable survival rates when compared to radical surgery; however, its widespread application has been limited by the complexity of the protocol, associated toxicity, and a high treatmentrelated mortality rate. The mortality rate in the two largest U.S. series with the longest follow-up is 4 to 5%. In comparison, the mortality rate for most modern cystectomy series is 1 to 2%. In addition, a significant number of patients ultimately require a salvage cystectomy, which is associated with increased morbidity when compared to primary cystectomy. In some series local recurrence of bladder cancer is as high as 50 to 60% despite completion of bladder preserving therapy. Transitional cell carcinoma is considered a chemosensitive cancer. The standard treatment of metastatic bladder cancer is MVAC,

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which is a combination of methotrexate, vinblastine, Adriamycin, and cisplatin. MVAC has an objective response rate of approximately 70% and a complete response rate of approximately 20%. However, long-term survival is rare, and with MVAC therapy, the 2-year survival is approximately 20%. At many centers, MVAC has been replaced by a combination of gemcitabine and cisplatin, which appears to produce comparable response rates with fewer toxic effects. As many as 50% of patients with clinically localized disease have micrometastases, and present with overt metastatic disease within 5 years of cystectomy. Therefore, chemotherapy also is advocated in the adjuvant setting for high-risk, localized disease.

Prostate Cancer Epidemiology Prostate cancer is the most common cancer in men and the second most common cause of cancer-related death in the United States. Each year, approximately 189,000 cancers are diagnosed, representing approximately 30% of all cancers diagnosed in men, and approximately 30,000 deaths results from prostate cancer.15 It is estimated that in the United States, one in six men will be diagnosed with prostate cancer during their lifetime. Since the widespread use of screening prostate-specific antigen (PSA) in the late 1980s, the incidence of prostate cancer has dramatically increased; however, after about 1990, the death rate from prostate cancer has been declining. It is often suggested that this decline in prostate cancer mortality has resulted from increased screening and early detection of prostate cancer. Family history, race, and environmental factors determine the risk of prostate cancer. Approximately 15 to 25% of patients diagnosed with prostate cancer report having at least one blood relative with the same diagnosis.38,39 Men with a father or a brother with prostate cancer are twice as likely to develop prostate cancer when compared with men with no family history. The risk of prostate cancer is directly related to the number of affected family members and if three first-degree relatives are affected, the relative risk may be as high as 11. In the United States, the risk of prostate cancer is also related to race. African Americans have a higher incidence of prostate cancer than do whites, while Hispanics and Asians have a lower incidence than whites. Environmental factors also affect the risk of prostate cancer. There is scientific evidence suggesting that the risk of prostate cancer can be lowered by a low-fat diet, as well as by various nutritional supplements including lycopene, vitamin E, and selenium.40

Prostate Cancer Screening Until prostate cancer metastasizes or becomes locally advanced, it does not generally cause symptoms. Most prostate cancers are diagnosed based on an elevated PSA or an abnormal digital rectal examination (DRE) of the prostate. PSA is a serine protease that is synthesized by the prostate epithelium and is elevated in prostate cancer. A PSA greater than 4 ng/mL is considered abnormal. Approximately 25% of patients with a PSA greater than 4 ng/mL will have a positive prostate biopsy, which establishes the diagnosis of prostate cancer. Approximately 50% of patients with both an elevated PSA and an abnormal DRE will have a biopsy positive for prostate cancer. Both BPH and prostate cancer increase serum PSA. Therefore, in an effort to improve the accuracy of PSA for predicting prostate cancer, several variations of the PSA test have been proposed, including age-specific PSA (higher normal PSA ranges for older age groups), PSA density (PSA/size of prostate measured on ultrasound), PSA

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

B

C

FIG. 39-18. Indiana pouch. A . An ileocecal segment is used to construct a continent reservoir that is emptied by periodic catheterization. B . The ileocecal segment is detubularized and (C ) fashioned into a pouch. The terminal ileum is plicated and brought to the abdominal wall, creating a catheterizable stoma. [Reproduced with permission from Carroll PR: Urinary diversion and bladder substitution, in Tanagho E, McAninch J (eds): Smith’s General Urology, 14th ed. Norwalk, CT: Appleton & Lange, 1995, p 457.]

velocity (change in PSA/year), and percent-free PSA (free PSA/total PSA). The rationale for using percent-free PSA is based on the observation that a lower fraction of serum PSA is free and not bound to serum proteins in men with prostate cancer than in men with BPH. The American Cancer Society recommends offering annual prostate cancer screening to men starting at 50 years of age who have at least a 10-year life expectancy. Additionally, the society recommends offering PSA screening at 45 years of age in African American men and in men with a family history of prostate cancer. However, the value of screening is debated within the medical community, and this debate is reflected by the conflicting guidelines published by several medical and health care organizations.41 Randomized prospective studies are currently being conducted to address the role of prostate cancer screening. Several issues contribute to the controversy regarding annual screening. PSA testing has a relatively low positive predictive value, resulting in a high number of “unnecessary” prostate biopsies. Based on autopsy studies, approximately 30% of men older than 50 years of

age have histologic prostate cancer; however, only a small fraction of these men will actually die from prostate cancer or even progress to clinically symptomatic disease. Prostate cancer often has a long and indolent course and occurs in older men, and as a result, many men with histologic prostate cancer eventually die of other, unrelated causes. Finally, the morbidity, such as incontinence and impotence, associated with the available treatments can significantly impact quality of life.

Work-Up Despite the controversy surrounding prostate cancer screening, it is important to point out that most cancers detected as a result of an elevated PSA or abnormal DRE are clinically significant cancers that should be treated in men with at least a 10-year life expectancy. The diagnosis of prostate cancer is made by biopsy. Using transrectal ultrasound guidance, the biopsy needles are directed at the peripheral zones where prostate cancer tends to develop. Prostate cancer is graded by the pathologist using the Gleason system. The two most predominant histologic patterns of the prostate cancer are assigned

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FIG. 39-19. Orthotopic neobladder. A and B . A continent reservoir is created by detubularizing a segment of ileum, (C ) fashioning the bowel into a pouch, and ( D ) anastomosing the neobladder to the urethra. [Reproduced with permission from Carroll PR: Urinary diversion and bladder substitution, in Tanagho E, McAninch J (eds): Smith’s General Urology, 14th ed. Norwalk, CT: Appleton & Lange, 1995, p 457.]

a Gleason grade, on a scale from 1 to 5. The two Gleason grades are added to give a Gleason score, on a scale from 2 to 10. Tumors with Gleason scores of 8 to 10 are considered highgrade tumors, and tumors with Gleason scores of 5 to 7 are considered intermediate-grade tumors. High-grade prostatic intraepithelial neoplasia (PIN) is considered a premalignant lesion that may indicate the presence of adjacent cancer. Given the possibility for sampling error, the presence of PIN in a biopsy that is negative for prostate cancer is an indication for repeating the biopsy; a repeat biopsy will be positive for prostate cancer in approximately 40% of cases. Prostate cancer is most commonly staged using the TNM system. The most common sites of metastasis for prostate cancer are the axial bones and pelvic lymph nodes. For the majority of patients diagnosed with prostate cancers, no formal metastatic work-up is

necessary. However, a PSA greater than 20 ng/mL or a PSA greater than10 ng/mL in a patient with a Gleason score 8 to 10 tumor is associated with an increased risk of metastatic disease, and a bone scan and pelvic CT scan should be performed. In addition, any patient complaining of bone pain should undergo a bone scan.

Treatment Localized Prostate Cancer. Prostate cancer tends to progress slowly and have a long, natural history. Therefore, treatment for localized prostate cancer is generally offered to patients with at least a 10-year life expectancy. Patients with high-grade tumors (Gleason score of 8 to 10) may represent an exception to this rule; without treatment, they are at a significantly higher risk of developing symptomatic disease and dying from their disease. Therefore, in these patients, curative therapy should be considered

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regardless of life expectancy. The treatment options for localized prostate cancer can be broadly categorized as involving surgery or radiation therapy. The most commonly performed surgical procedure is a radical retropubic prostatectomy (RRP) (Fig. 39-20). A pelvic lymph node dissection is generally performed for staging purposes at the time of surgery. The most significant complications associated with surgery are urinary incontinence and erectile dysfunction, which occur in approximately 5 to 10% and 14 to 30% of cases, respectively.42,43 During RRP, care should be taken to avoid injuring the urinary sphincter located just distal to the apex of the prostate. The neurovascular bundles that run along the posterolateral border of the prostate contain the cavernous nerves, which are responsible for erectile function. Care should be taken to separate the neurovascular bundle from the prostate and preserve it during surgery. Other less frequently employed surgical options include perineal radical prostatectomy and cryotherapy. Options for radiation therapy include external radiation therapy (XRT) and brachytherapy. With most XRT protocols, 60 to 80 Gy is delivered by conformal radiotherapy. The primary genitourinary side effects following XRT include frequency, dysuria, hematuria, and decreased bladder capacity. The primary gastrointestinal side effects include diarrhea, rectal pain, and rectal bleeding. The sexual dysfunction following XRT develops gradually and 40 to 50% of previously potent men are impotent 5 years following treatment. Brachytherapy involves the percutaneous placement of radioactive seeds into the prostate. Although the side effects associated with brachytherapy are generally less severe than those associated with XRT, brachytherapy is less effective than XRT for treatment of highrisk prostate cancer. There are currently no definitive studies demonstrating that surgery or XRT provides better cancer control. Although brachytherapy appears effective based on initial results treating patients with favorable prognosis, long-term follow-up is not yet available. In several studies, including several phase III studies, long-term use of androgen-ablative therapy in conjunction with XRT improves survival. However, studies assessing the role of neoadjuvant androgenablative therapy before RRP demonstrate no added benefit when compared to RRP alone.

Metastatic Prostate Cancer. The first-line therapy for metastatic prostate cancer is androgen-ablative hormone therapy. Since Charles Huggins won the Nobel Prize in 1966 for discovering the therapeutic effects of androgen ablation on metastatic prostate cancer, the fundamental principles for treating metastatic prostate cancer have not changed. Androgen-ablation is accomplished by performing bilateral orchiectomies or by administering gonadotropin-releasing hormone (GnRH) agonist. Testosterone synthesis by the Leydig cell in the testicles is stimulated by luteinizing hormone (LH) from the pituitary. The release of LH requires a pulsatile discharge of GnRH. Therefore, a constant GnRH stimulation paradoxically results in inhibition of LH and testosterone. Nonsteroidal antiandrogens such as flutamide and bicalutamide are often added to block the low levels of androgens produced by the adrenal medulla. Testis Cancer Testicular cancer is the most common cancer in men between the ages of 20 and 35 years.15,44 There are approximately 7000 new cases and 400 deaths related to testis cancer per year. For more than 90% of patients, testicular cancer is curable. Any patient with a solid testicular mass, which has been confirmed on ultrasound, is considered

to have testicular cancer until proven otherwise, and should undergo a radical orchiectomy to make a definitive diagnosis. Prior to surgery, serum markers for testicular cancer should be obtained. The two markers used in routine clinical practice are human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH). When performing a radical orchiectomy, the surgery should be performed by an inguinal approach rather than a scrotal approach. The metastatic spread of testicular cancer is ordered and predictable. The primary metastatic landing sites for left and right testicular cancers are the para-aortic and the interaortocaval nodes in the retroperitoneum, respectively. The lymphatic drainage of the scrotum, on the other hand, is to the inguinal nodes. If the scrotum is surgically violated by performing a scrotal orchiectomy, metastatic spread to both the retroperitoneal and the inguinal nodes becomes possible. Following an orchiectomy for localized germ cell tumor, hCG (half-life of 5 to 7 days) and FSH (half-life of 24 to 36 hours) levels that were elevated before surgery should normalize. The diagnosis of testicular cancer is made based on the pathology of the orchiectomy specimen. Approximately 95% of testicular cancers are germ cell tumors, while approximately 4% of testicular cancers are nongerm cell tumors such as Leydig cell tumors and Sertoli cell tumors. Germ cell tumors are further classified as seminomas and nonseminomas.45 For clinically localized seminomas, the standard of care is to treat the retroperitoneum with radiation to prevent nodal recurrence, although observation and close follow-up are also reasonable.46 For clinically localized nonseminomas that are at high risk for recurrence,47 the options include a prophylactic retroperitoneal lymph node dissection, two cycles of prophylactic chemotherapy or observation with very close followup. Patients electing observation should understand that there is a 30% risk of retroperitoneal recurrence. The treatment of metastatic germ cell tumor generally involves chemotherapy. Most chemotherapy protocols employ a combination of bleomycin, etoposide and cis-platinum.

Penile Cancer Penile cancer is rare in the United States, representing less than 1% of all tumors in men.15 However, in certain regions of Africa and South America, penile cancer represents 10 to 20% of all malignancies. The majority of penile malignancies are squamous cell carcinomas. The diagnosis is made on biopsy. The primary lesion should be completely resected, whenever possible, to prevent the morbidities associated with local invasion. Penile cancer spreads in a predictable pattern to the inguinal lymph nodes and then to the pelvic lymph nodes.48 Patients who present with enlarged pelvic lymph nodes on CT scan should undergo a diagnostic pelvic lymph node dissection.49,50 Pathologically confirmed pelvic lymph node metastasis should be further treated with chemotherapy, and no further surgical therapy is indicated. For patients without involvement of pelvic lymph nodes, the inguinal lymph nodes are evaluated. However, primary penile tumors often have an infectious component that can result in enlargement of the inguinal lymph nodes. Therefore, following resection of the primary tumor, the patient should be treated with antibiotics for 6 weeks before evaluating the inguinal nodes. Following antibiotic therapy, patients with palpable inguinal lymph nodes should undergo an inguinal lymph node dissection. In addition, all patients with high-grade primary penile tumors or primary tumors invading the corporal bodies should undergo an inguinal lymph node dissection regardless of whether the nodes are palpable or not. Approximately one-third of patients with disease in the inguinal nodes are cured following an inguinal node dissection.

Dorsal venous complex

Neurovascular bundle

A

C

E

B

Rectourethral muscle

D

FIG. 39-20. Radical retropubic prostatectomy. A . The dorsal venous complex over the apex of the prostate is ligated with a distal stitch and a proximal stitch, and then divided. B . The neurovascular bundles containing the nerves for erectile function are dissected off the prostate. C . The urethra is divided and the prostate is separated from the anterior rectum. D . The vasa deferentia are divided and the seminal vesicles are dissected and removed with the specimen. E . The bladder neck is reanastomosed to the distal urethral stump.

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UROLOGIC INFECTIONS Cystitis Cystitis is inflammation of the bladder mucosa and is usually caused by bacterial organisms. E. coli is the most common cause of urinary tract infection (UTI), including cystitis. Other common causative organisms include Proteus, Klebsiella, Enterococcus, and Staphylococcus saprophyticus. Women are at a higher risk for UTI than men because their urethra is shorter. Fecal flora contaminating the vaginal mucosa can ascend through the female urethra. Certain bacterial factors, such as type 1 pili found on some strains of E. coli, mediate adhesion and are more likely to cause UTI.51 In addition, certain host factors such as vaginal pH, can promote vaginal colonization and UTI.52 Symptoms of cystitis include urinary frequency, urgency, and dysuria. Uncomplicated cystitis does not generally cause fevers or leukocytosis. Patients with voiding symptoms can be worked up with a urinalysis. However, a urine culture provides a more definitive diagnosis of a UTI than a urinalysis. Important considerations when obtaining a urine culture have been previously discussed in this chapter. Bacterial UTI in women should be treated with 3 days of antibiotics. In men, bacterial UTI should be treated with 7 days of antibiotics and younger men should be evaluated for correctable structural anomalies with an IVP or CT scan with IV contrast, and a cystoscopy. Asymptomatic bacteriuria occurs in approximately 30% of elderly nursing home residents and in 5% of sexually active women. Asymptomatic bacteriuria is the rule in patients with chronic indwelling Foley catheters. Most asymptomatic bacteriuria does not need to be treated. However, asymptomatic patients with ureasplitting organisms should be treated with antibiotics. Pregnant women with bacteriuria should also be treated as they are at an increased risk for developing pyelonephritis.

Pyelonephritis Pyelonephritis refers to inflammation of the renal parenchyma and collecting system. It is a clinical diagnosis that is made based on the presence of fever, flank pain, and infected urine. Older patients and young children may present with less-specific symptoms such as mental status changes, abdominal discomfort, and low-grade fevers. The most common causative agents are gram-negative bacteria such as E. coli, Proteus, Pseudomonas, and Klebsiella. Most bacterial agents gain access to the urinary system through the urethra and ascend to the kidney. Therefore, women are generally more susceptible to UTI and pyelonephritis because of the shorter urethra in females compared to males. Patients presenting with signs and symptoms of pyelonephritis should have a urine culture and serial blood cultures. The results of the urine culture may not be available for 48 hours; therefore, a urinalysis can be used to support a presumptive diagnosis of pyelonephritis. Healthy adults with no significant comorbidities can be treated as an outpatient; however, most patients diagnosed with pyelonephritis are admitted to the hospital. Broad-spectrum IV antibiotics, such as ampicillin and gentamicin, should be started until the results of the urine culture are available and a more selective antibiotic can be identified. When patients are afebrile, they can be discharged on oral antibiotics. Uncomplicated pyelonephritis should be treated for a total of 14 days while pyelonephritis associated with structural or functional abnormalities should be treated for 21 days. In patients being treated for pyelonephritis, after 24 hours of antibiotic therapy, the urine should be sterile and leukocytosis should

be minimal. However, patients often continue to have periodic fever spikes for several days after initiating treatment. This is believed to be a result of resolving inflammation in the kidney rather than an active infection. With appropriate treatment, the magnitude of each subsequent fever spike should decrease. In most patients, no radiologic studies are initially necessary. However, if there is no clinical improvement following 2 to 3 days of treatment, a CT scan with IV contrast should be obtained. Patients with renal insufficiency or allergy to IV contrast can have an MRI, a renal ultrasound, or a CT scan without contrast. In select patients with pyelonephritis, the upper tracts should be imaged at the time of presentation. In selecting patients for early radiologic study, the most important principle to keep in mind is that an obstructed and infected urinary system is a surgical emergency that requires prompt intervention to establish drainage. Therefore, the upper tracts should be studied in any patient with a history of kidney stones, anatomic abnormalities such as a ureteropelvic junction obstruction, or malignancies that may cause extrinsic compression of the urinary system. Options for emergently draining an obstructed kidney include percutaneous nephrostomy tube placement and cystoscopic placement of a ureteral stent. Bladder outlet obstruction causing bilateral hydronephrosis can be relieved by the placement of a Foley catheter. Other findings on CT scan and MRI may require surgical intervention. Small renal and perirenal abscesses (Fig. 39-21) can be conservatively managed with antibiotics in clinically stable patients.53 However, if there is inadequate clinical improvement or if the abscess is large, the infectious collection should be immediately drained. Drainage is preferably accomplished percutaneously. Emphysematous pyelonephritis is often seen in older diabetic patients and represents a medical emergency (Fig. 39-22). Air bubbles produced by gas-forming organisms can be seen in the renal parenchyma on x-ray or CT scan. Emphysematous pyelonephritis should be promptly treated with percutaneous drainage; if there is no evidence of clinical improvement, an urgent nephrectomy should be performed.54 In adult patients, there is no permanent sequela following successful treatment of pyelonephritis. However, pyelonephritis in an infant kidney that is still developing can be devastating.

FIG. 39-21. Right perirenal abscess. CT scan of a 40-year-old patient presenting with fever, chills, and flank pain. Patient improved on antibiotics after the perirenal collection was drained percutaneously.

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A

B FIG. 39-22. Emphysematous pyelonephritis. A . CT scan of a 52-yearold diabetic patient presenting with sepsis. Note the air in parenchyma formed by gas-producing organisms. B . Picture of kidney following emergent nephrectomy.

Pyelonephritis can lead to permanent parenchymal scarring and loss of renal function.55 The most common abnormality resulting in pyelonephritis in infants and children is ureteral reflux. Ureteral reflux can carry an infectious organism from the bladder to the kidney, and severe reflux can cause hydronephrosis and urinary stasis. Therefore, pediatric patients with cystitis or pyelonephritis should be worked up with a renal ultrasound and a voiding cystourethrogram. Any pediatric patient at risk for pyelonephritis should be treated with long-term antibiotic prophylaxis.

Xanthogranulomatous Pyelonephritis Xanthogranulomatous pyelonephritis (XGP) is a rare form of chronic pyelonephritis. The presumptive diagnosis of XGP is made on CT scan or MRI based on the presence of calcification and large cystic lesions replacing the majority of the parenchyma in patients with chronic flank pain and low-grade fevers. A nephrectomy should be performed to rule out a malignant process. Following the nephrectomy, a definitive diagnosis of XGP is made histologically by the

FIG. 39-23. Xanthogranulomatous pyelonephritis. A . Note excrescences surrounding calyces (grossly yellow). B . Micrograph showing clear cells, which are lipid-laden macrophages that may resemble clear cell renal cell carcinoma. A stone is often present in the kidney in cases of xanthogranulomatous pyelonephritis.

presence of inflammatory cells and large lipid-laden macrophages (Fig. 39-23).

Fungal Infections Most fungal infections of the urinary tract are opportunistic infections. They tend to occur in debilitated or immunocompromised patients. Candida is responsible for the vast majority of fungemia and funguria. Risk factors for fungal infection include immunosuppression, diabetes, antibiotic use, steroid therapy, and long-term use of urinary catheters.56 On cystoscopy, affected areas may appear as white patches on the bladder wall. Upper tract radiographic studies such as CT scan and IVP may demonstrate a fungal mass. For patients with fungal UTI, treatment is based on whether the infection is simple or complex. Simple fungal infections are diagnosed by a urine culture positive for more than 105 organisms/mL and are confined to the bladder. Simple fungal infections may be asymptomatic or they may cause irritable voiding symptoms such as dysuria and frequency. These infections are usually managed successfully by stopping any antibiotics, or removing urinary catheters

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and temporarily instituting intermittent catheterizations. Infections that do not resolve with these simple measures may require bladder irrigation with amphotericin B (50 mg/L of water administered at 42 mL/h).57,58 Complex fungal infections refer to infections involving the upper urinary tract or infections resulting in positive blood cultures. Complex fungal infections should be treated with IV antifungal agents. If fungal balls are present in the upper urinary tract, the effected kidney should be treated by percutaneously removing the fungal ball and directly irrigating the renal pelvis with amphotericin B. The gold standard for complex fungal infections is IV amphotericin B. Amphotericin B binds the ergosterol component of fungal cell walls and disrupts the cellular membrane. The half-life of amphotericin B is 15 days and resistance is unusual. Systemic effects, such as rigors, chills, and fevers, associated with treatment can be minimized by premedicating with steroid, meperidine, ibuprofen, and dantrolene.

Prostatitis Prostatitis is a common disease that accounts for approximately 8% of urology-related office visits. Prostatitis is diagnosed in men who complain of pain and discomfort that generally localizes to the perineal region.59 Although the term implies an inflammation of the prostate gland, often there is no clinical or histologic evidence of inflammation. Based on the clinical presentation, prostatitis can be categorized as acute or chronic. Acute prostatitis refers to a bacterial infection of the prostate that leads to system findings such as fever, chills, and leukocytosis. Chronic prostatitis includes all other forms of prostatitis associated with local symptoms. The most common causes of bacteria prostatitis are the same organisms in the fecal flora that are responsible for urinary tract infections, and include E. coli, Proteus, Klebsiella, and Pseudomonas. Patients with acute prostatitis are febrile and often complain of frequency, urgency, dysuria and a decreased urinary stream. Occasionally, patients may even present in shock with tachycardia and hypotension. On physical exam, the prostate is extremely tender to palpation, and the digital exam should be performed gently to prevent shedding bacteria into the blood stream. Laboratory exam will reveal an elevated white blood cell count and urinalysis and urine culture findings will be consistent with a bacterial infection. The treatment for acute bacterial prostatitis is similar to the treatment for pyelonephritis. Usually the treatment is initiated with broadspectrum IV antibiotics. When patients are afebrile and hemodynamically stable, treatment can continue with oral antibiotics for a total of 3 weeks. Chronic prostatitis can be subdivided into bacterial and nonbacterial prostatitis. Classically, chronic, bacterial prostatitis is characterized by recurrent urinary tract infections by the same organism. Treatment involves 30 days of antibiotic therapy with a fluoroquinolone or trimethoprim/sulfamethoxazole. Patients with local symptoms of prostatitis without a history of urinary tract infections can be assumed to have nonbacterial prostatitis. Nonbacterial prostatitis represents the vast majority of all cases of prostatitis and can be a very frustrating problem for both the patient and the treating physician. The etiology is poorly understood and a variety of treatments, including alpha blockers, antibiotics, anticholinergics, and benzodiazepines, have been used with inconsistent and modest results.

URINARY INCONTINENCE Urinary incontinence refers to unintended leakage of urine from the bladder. It is estimated that in the United States, more than 17 million

men and women suffer from urinary incontinence. The vast majority of patients treated for urinary incontinence are women past middleage. In the elderly population, approximately 50% of nursing home residents suffer from urinary incontinence. Approximately $26 billion is spent annually in the United States for management of this problem.60

Normal Voiding Physiology Urinary storage occurs in the bladder when there is a coordinated relaxation of the bladder wall muscle, and contraction of the urinary sphincter. Stimulation of beta-adrenergic receptors in the bladder leads to relaxation of the bladder wall. Contraction of the smooth and striated muscles in the urinary sphincter result from alphaadrenergic and cholinergic stimulation. Conversely, voiding occurs when there is a coordinated contraction of the bladder smooth muscle and relaxation of the urinary sphincter. Bladder wall contraction is mediated by the cholinergic receptors. Nitric oxide stimulates the nonadrenergic noncholinergic pathway, resulting in relaxation of the urinary sphincter. Normal voiding is coordinated by the pontine micturition center in the brain stem. Patients with neurologic insults affecting the brain stem or spinal column may suffer from a form of uncoordinated voiding known as detrusor–sphincter dyssynergia, where the bladder and sphincter contract at the same time during voiding, leading to high intravesical pressures. Neuronal connections from higher centers of the brain to the pontine micturition center regulate voluntary control of micturition. All disorders affecting the upper tract such as strokes and spinal cord injuries can lead to involuntary bladder contractions. As discussed in the section on urinary signs and symptoms, incontinence can be categorized as stress, urge, total, and overflow. A thorough history, including a history of voiding complaints, urologic diseases, obstetric events, and neurologic diseases should be obtained. Urinary tract infections can lead to urinary incontinence and should be ruled out. A focused neurologic exam should be performed, noting any sensory or motor deficits and decrease in anal tone. If overflow incontinence is suspected, a postvoid urinary residual should be checked by catheterization or bladder ultrasound. In female patients, a pelvic exam should be performed with the patient in stirrups. Prolapse of any pelvic structures should be noted. The patient should be asked to bare down to assess for stress incontinence or rotational descent of the bladder and proximal urethra. Rotational descent can be quantified with a “Q-tip test.” A lubricated cotton swab is inserted into the urethra and the patient is asked to bear down. If the angle of the cotton swab changes by more than 30 degrees, the patient is considered to have significant urethral descent.

Urodynamics Multiple categories of urinary incontinence may often coexist. For example, a patient may have both urge and stress incontinence. To better delineate the components of incontinence, a urodynamics test may be performed.61 To perform the test, a small catheter, usually 7F, with multiple channels is inserted into the bladder to allow simultaneous filling of the bladder and transducing of intraluminal pressures. There are four primary components to urodynamics testing. The first component is cystometry, which involves measuring detrusor pressures at various bladder volumes. Detrusor pressure, which is generated by the bladder wall, is calculated as the pressure measured in the bladder lumen minus the intra-abdominal pressure measured by a catheter in the rectum. As the bladder fills,

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FIG. 39-24. Urodynamic study demonstrating detrusor–external sphincter dyssynergia. Note the hyperactivity of the external sphincter (large black area) while the patient is voiding. The resulting outlet resistance can produce hydronephrosis and ultimately diminish renal function.

involuntary detrusor contractions are recorded and the bladder sensory function is assessed by noting when the patient feels the need to void. After filling the bladder, the patient is asked to void and evidence of detrusor–external sphincter dyssynergia is noted by monitoring external sphincter contractions by electromyography (Fig. 39-24). The second component of urodynamics is a pressure-flow study to assess for bladder outlet obstruction. A decreased urinary flow rate may result from either bladder outlet obstruction or a poorly contracting bladder. Therefore, both vesical pressure and maximum urinary flow rate are simultaneously measured to assess the bladder outlet. The third component is a urethral pressure study to assess the resistance provided by the urinary sphincter. To perform a urethral pressure study, the bladder is filled to 150 to 200 mL. The patient is asked to Valsalva and the abdominal pressure that produces urinary leakage is noted as the Valsalva leak point pressure. A Valsalva leak point pressure less than 60 mm H2 O is consistent with intrinsic sphincter deficiency. The fourth component to urodynamics is videourodynamics. The bladder is filled with radiographic contrast and the bladder is imaged in real time on a fluoroscopic screen. The relationship between the bladder, the urethra, and various pelvic landmarks can be noted, and the status of the bladder neck can be assessed during rest, Valsalva, and voiding.

Stress Urinary Incontinence Stress urinary incontinence occurs with increase in intra-abdominal pressure associated with activities such as coughing, laughing, or exercise.62 In women, stress incontinence can result from loss of urethral support, intrinsic sphincter deficiency or a combination of the two. The loss of urethral support can lead to rotational descent of the bladder. This leads to a change in the normal angle between the urethra and proximal bladder.63 The relationship between these two structures is important for proper functioning of the urinary sphincter. In addition, a lax urethral support can lead to poor transmission of intra-abdominal pressure, which normally helps to coapt the urethral mucosa and form a water-tight seal. A variety of conditions contribute to the structural changes associated with stress incontinence. Labor and childbirth have long been associated with the development of stress continence.64 Prolonged labor, number of childbirths, and use of delivery forceps have all been linked to subsequent development of stress incontinence—the most important mechanism appears to be partial disruption of the innervation to the pelvic floor musculature.65 Other factors associated

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with the development of stress incontinence include aging, pelvic surgery, trauma, hypoestrogenic states, and neurologic conditions that result in denervation of the urinary sphincter. In men, stress incontinence is most commonly caused by intrinsic sphincter deficiency following radical prostate surgery or transurethral prostate resection. Mild stress incontinence may be improved by conservative measures such as using estrogen supplements in postmenopausal women, pelvic floor exercises, and timed voiding. However, the most effective treatment options for stress incontinence involve surgery. In female patients, a urethral sling procedure can be performed to increase urethral resistance and to correct mild to moderate degrees of urethral prolapse. A variety of sling techniques have been described, however most procedures involve placing a sling material around the urethra and tacking the material to the rectus fascia.66 In male patients with stress incontinence, the most effective procedure is an artificial urinary sphincter. The artificial sphincter has three components. A fluid-filled sphincter is placed around the bulbar urethra, a pump is placed in the scrotum and a reservoir is placed in the prevesical space. The sphincter increases urethral resistance and helps prevent incontinence. When the patient wishes to void, he opens the sphincter by compressing the pump in his scrotum and moving fluid from the sphincter to the reservoir.

Urge Incontinence An overactive bladder is characterized by involuntary detrusor contractions. If these involuntary contractions generate sufficient pressure to overcome the urethral resistance, urinary incontinence results. Two terms distinguish the etiology of overactive bladders. Involuntary bladder contractions secondary to an upper tract neurologic insult, such as a stroke or spinal cord injury, is referred to as detrusor hyperreflexia. Involuntary contractions resulting from irritation of the bladder itself is termed detrusor instability. Common causes of detrusor instability include urinary tract infections, bladder prolapse, stress incontinence and bladder outlet obstruction. When possible, the underlying etiology for an overactive bladder should be addressed. For example, if stress incontinence is the primary problem, the urge incontinence will resolve in more than half of patients after surgical treatment for stress incontinence. The vast majority of patients with overactive bladders do not have a clearly identifiable cause and symptomatic treatment is employed. Anticholinergics are effective, particularly when combined with timed voiding. Various biofeedback programs are effective for motivated patients with milder symptoms. A permanent sacral nerve stimulator can be implanted to inhibit bladder contractions and help prevent urinary incontinence.

Total Incontinence Total incontinence refers to continuous leakage of urine and implies that a fistula exists between the urinary tract and the skin or vagina.67 In industrialized countries, the most common cause of a vesicovaginal fistula is routine pelvic surgery such as vaginal hysterectomies, which account for approximately 75% of cases. In developing countries, the major cause of vesicovaginal fistulas is birth trauma. Other causes include malignancy, inflammatory bowel disease, and urinary tuberculosis. The diagnosis can be confirmed by instilling dye into the bladder and evaluating the color of the draining vaginal fluid. Cystoscopy and vaginoscopy can be performed to localize the fistula. The treatment generally involves surgical repair; however, if a fistula is identified immediately following the responsible iatrogenic

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injury, a trial of conservative management with catheter drainage of the bladder is reasonable. The principles for surgical repair are the same as for repair of fistulas in other parts of the body. A tension-free closure with multiple, nonoverlapping lines of closure is critical to the success of the repair. When possible, vascularized tissue should be interposed between the layers of closure.

Overflow Incontinence Overflow incontinence, often termed false incontinence, is secondary to urinary retention, resulting either from an obstruction or an atonic bladder. Patients with new onset of urinary incontinence should be catheterized or have a bladder ultrasound to check for a postvoid residual. If the urinary retention is secondary to bladder outlet obstruction, the cause of the obstruction should be addressed. Urinary retention following pelvic surgery is usually temporary and resolves following several days of catheter drainage or intermittent catheterization. Spinal cord injury above the level of the sacrum can result in a hyperreflexic bladder. However, during the immediate 6 to 8 weeks following the injury, there is a period of bladder atony, termed spinal shock. Other causes of an atonic bladder include diabetes, sacral spinal cord injury, and pernicious anemia. If long-term management is required for an atonic bladder, clean, intermittent catheterization is a safe and effective option.

TRAUMA Kidney and Ureter Approximately 10% of traumas involve the urologic system, most commonly the kidneys. The best study for evaluating the kidneys is a helical abdominal CT scan with IV contrast. A CT scan should be performed for all penetrating traumas. For adult patients with blunt trauma, a CT scan should be obtained in patients with gross hematuria, or with microscopic hematuria and systolic blood pressure less than 90 mm Hg at any point during the transport and resuscitation.68 Approximately one-third of renovascular injuries present with complete absence of hematuria, and, therefore, mechanism of injury and associated clinical findings, such as flank contusions and lower rib fractures, should also prompt a CT scan.69,70 Pediatric patients are able to maintain blood pressure despite an almost 50% loss of circulating volume. Therefore, hypotension is a poor indicator for radiologic work-up. All pediatric patients with gross hematuria should have a CT scan, and all pediatric patients with microscopic hematuria and potential renal trauma based on the mechanism of injury should have a CT scan. The most commonly applied staging system for renal injury was developed by the American Association for the Surgery of Trauma (Table 39-2 and Fig. 39-25). Approximately 95% of renal traumas are grade 1. Approximately 98% of renal injuries can be managed nonoperatively. The only absolute indications for surgical management of a renal injury are persistent bleeding resulting in hemodynamic instability or an expanding perirenal hematoma. Relative indications for surgical management include major urinary extravasation, vascular injury, and devitalized parenchymal tissue. Studies show that even large urinary extravasations will resolve with conservative management.71 Smaller vascular injuries resulting in devitalized tissue also can be managed without surgery; however, if the amount of devitalized tissue exceeds 20% of the renal tissue, surgical management leads to quicker resolution of the injury and to fewer subsequent complications.72 Patients managed nonoperatively should be placed on bedrest until resolution of gross hematuria. After resuming ambulation, the

Table 39-2 Staging System for Renal Injury Developed by the American Association for the Surgery of Trauma Grade 1 2 3 4

5

Description of Injury Contusion or nonexpanding subcapsular hematoma No laceration Nonexpanding perirenal hematoma Cortical laceration 1 cm without urinary extravasation Laceration: through corticomedullary junction into collecting system or Vascular: segmental renal artery or vein injury with contained hematoma Laceration: shattered kidney or Vascular: renal pedicle injury or avulsion

source: From Moore EE, Shackford SR, Pachter HL, et al: Organ & injury scaling: Spleen, liver, and kidney. J Trauma 29:1664, 1989.

patient should be carefully monitored for recurrence of gross hematuria, which requires reinstitution of bedrest. Surgical exploration should be performed following CT staging when possible. If the patient requires immediate exploration for hemodynamic instability and a CT scan cannot be performed, a one-shot intravenous pyelogram (1 mL/kg of body weight of 30% contrast administered 10 minutes before x-ray) should be performed intraoperatively to evaluate the kidneys and confirm the presence of a functioning contralateral kidney. Surgical exploration should be performed through a midline approach. The renal vessels should be identified and controlled prior to opening Gerota’s fascia, in order to allow the vessels to be rapidly occluded if massive bleeding is encountered. Injuries to the collecting system should be repaired by a watertight closure. Devitalized tissue should be excised and meticulous hemostasis should be obtained by ligating open segmental vessels. If bleeding cannot be controlled or only minimal vitalized tissue remains, a nephrectomy should be performed. Ureteral injuries are rare, with the majority of injuries resulting from penetrating trauma. The diagnosis of ureteral injuries can be challenging as they often present without hematuria. Ureteral injuries are often discovered during radiographic work-up or abdominal exploration for related injuries. If a ureteral injury is suspected, an intravenous pyelogram, a retrograde pyelogram, or a contrast CT scan should be obtained. When performing a CT scan, delayed images should be obtained after the contrast has entered the collecting system. Surgical repair depends on the level of injury and the length of the injured segment. Important principles for surgical repair include a tension-free, water-tight closure after widely d´ebriding the injured segment. For coverage of large ureteral defects, interposition of intestinal segments or bladder flaps may be required to achieve a tension-free repair. The adventitia surrounding the ureter should be carefully preserved to maintain the tenuous, ureteral blood supply.

Bladder Hematuria, gross or microscopic, is the hallmark of bladder injury. The vast majority of bladder injuries are found in patients with pelvic fractures.73,74 More than 90% of patients diagnosed with bladder injury have a pelvic fracture and approximately 10% of pelvic fractures are associated with bladder ruptures. Therefore, radiographic imaging should be obtained in all patients with hematuria and pelvic

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Grade I

Grade II

Grade IV

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Grade III

Grade V

FIG. 39-25. Grading for renal trauma.

fractures, or in patients with penetrating trauma to the pelvis and lower abdomen. Rarely, bladder injury can occur in the absence of a pelvic fracture. Therefore, radiographic imaging also should be considered if pelvic contusions or urethral injuries are present. A retrograde cystogram is the most accurate test for ruling out a bladder rupture. When performing a retrograde cystogram, it is critical to adequately distend the bladder (400 mL or 40 cm H2 O) and obtain a postdrainage film to look for extravasation of contrast. An alternative study is a CT cystogram, which can be obtained at the same time the abdomen and pelvis are imaged for related injuries. The management of bladder injury depends on the site of rupture. Extraperitoneal ruptures can usually be managed conservatively with prolonged catheter drainage; however, intraperitoneal ruptures should be explored and surgically repaired.

posterior urethral injuries occur in patients with a pelvic fracture and approximately 10% of pelvic fractures are associated with urethral injuries. Although a suprapubic tube provides effective urinary drainage without risking further disruption of the urethra, a urethral Foley should be placed across the injury when possible. If the disruption

Urethra Patients with urethral injury resulting from trauma classically present with blood at the meatus and inability to void. Other potential findings include a perineal hematoma (Fig. 39-26) and a “high-riding” prostate on digital rectal exam. If any of these findings are present, a retrograde urethrogram should be performed before attempting to catheterize the bladder. To perform a retrograde urethrogram, a small Foley catheter is placed just inside the meatus and the Foley balloon is inflated with 1 to 2 mL of water. Lateral decubitus films are taken while 30 to 50 mL of radiographic contrast is gently injected through the catheter. When feasible, performing the study under fluoroscopy is preferred. Urethral injuries are categorized as posterior or anterior injuries.

Posterior Urethra Trauma to the posterior urethral, which includes the prostatic and membranous urethra, occurs in the context of pelvic fractures. The statistics are similar to that of bladder trauma.75 More than 90% of

FIG. 39-26. Perineal hematoma contained by Colles’ fascia.

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is only partial, this can be accomplished by placing a guidewire into the bladder by using a flexible cystoscope, or even a flexible ureteroscope, and placing a catheter over the wire. If complete urethral disruption is present, two flexible cystoscopes, inserted through the meatus as well as through a suprapubic cystostomy, can be used to align the urethra.76 A guidewire can be placed across the aligned urethra to permit insertion of a Foley catheter. Early urethral alignment can often obviate the need for formal, surgical repair of the urethra. If a completely disrupted urethra cannot be aligned, a definitive repair should be performed in 4 to 6 months. Early exploration following pelvic trauma should not be performed in order to avoid disrupting the pelvic hematoma and causing additional bleeding.

Anterior Urethra The anterior urethra includes the bulbous and penile urethral. Anterior urethral traumas are usually isolated injuries that most commonly result from a straddle injury. Anterior urethral injury can also occur as a result of direct trauma to the penis. Pelvic fractures are rare in patients with anterior urethral injuries. More distal injuries are contained by Buck’s fascia and resulting hematomas dissect along the penile shaft (Fig. 39-27). More proximal injuries to the anterior urethra may be contained by Colles’ fascia and produce a perineal hematoma. The treatment of choice for most blunt and penetrating injuries is immediate exploration, d´ebridement, and direct repair. An exception is an anterior urethral injury resulting from a highvelocity gunshot, which should be managed with a suprapubic cystostomy and delayed repair after clear demarcation of injured tissues.

Proximal injuries to the anterior urethra can be approached through a perineal incision, and more distal injuries can be approached by making a circumferential, subcoronal incision and degloving the penis.

Penis Penetrating injuries to the penis are rare. Injuries to the penile corporal should be repaired by closing ruptures of the tunica albuginea. Blunt or penetrating penile injuries resulting from an accident should be evaluated with a urethrogram. Urethral injuries should be managed as described in the section on urethral trauma. Penile fractures represent a traumatic rupture of the tunica albuginea. Most penile fractures occur during sexual intercourse with the woman on top of the man. The erect penis slips out of the vagina and is bent against the pubis and perineum. Patients describe a cracking sound followed by immediate loss of penile rigidity and onset of penile swelling. Patients providing such a history should be immediately explored in the operating room using a circumferential, subcoronal incision to deglove the penis. Generally, no further radiologic work-up is needed. In cases where the history and physical examination is equivocal, a cavernosogram and a urethrogram can be performed. The most common cause of penile amputations is self-mutilation. When possible, reimplantation should be attempted. Reattachment can be attempted following up to 6 hours of warm ischemia. During surgery, the structures that should be reapproximated include the urethra, the corporal bodies, the dorsal artery and vein, and the dorsal nerves. In cases of self-mutilation, psychiatric consultation is essential to prevent further injury and to control the psychiatric illness.

Testis The most common causes of testicular injury are assaults and sports injuries. Blunt trauma to the scrotum can disrupt the vessels surrounding the testicles and result in a hematocele. Small traumatic hematoceles do not require surgical intervention. An ultrasound should be performed to confirm that the testicles are intact. Rupture of the testicle itself is rare and requires immediate exploration and surgical repair. The testicles should be immediately explored with no need for an ultrasound if physical findings such as a large hematocele, large hematoma, or gross disruption of the testicular wall are found, suggesting testicular rupture. At the time of surgery, the hematoma should be evacuated and the tunica albuginea should be closed. Penetrating scrotal injuries should be explored, and amputated testicles can often be successfully reimplanted when warm ischemia time is less than 6 hours.

STONE DISEASE Etiology

FIG. 39-27. Rupture of a corporal body contained by Buck’s fascia.

Stone disease is one of the most common urologic diseases, affecting one in eight white men by age 70 years.77,78 Stone disease is most common in 20- to 40-year-olds and is three times more common in men than in women. The prevalence of urinary tract stone disease has been estimated at 2 to 3%. For patients developing a stone, the risk of recurrent stone formation within 5 years may be as high as 50%.79 Therefore, successful treatment of stone disease not only involves management of the acute stone, but also long-term medical management to prevent future stone formation.

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FIG. 39-28. A . Plain x-ray of a large, right ureteral stone somewhat obscured by the spinal column. B . Oblique view of the same patient clearly reveals the large stone in the right midureter. C . A retrograde pyelogram was performed to better define the anatomy of the urinary collecting system.

Acute Kidney Stone Presentation An acute stone is defined as a urinary stone obstructing the kidney or ureter, and causing symptoms. The classic symptoms of an obstructing kidney stone include colicky flank pain and hematuria, often accompanied by nausea and vomiting. If the stone moves down the ureter, the pain may localize to the ipsilateral lower abdomen. A stone impacted in the distal, intramural ureter may produce pain referred to the inguinal and perineal areas. On physical exam, costovertebral angle tenderness can usually be appreciated. The hematuria accompanying stone disease may be microscopic or gross. However, approximately 15% of acute renal stones present without hematuria. Patients with a superimposed urinary tract infection may present with fever and irritative voiding symptoms. Patients with an infected urinary system and a completely impacted stone may even present with signs and symptoms of sepsis.

Radiologic Work-Up The diagnosis of a urinary stone can be confirmed radiologically. A plain x-ray of the abdomen and pelvis is the simplest test to obtain (Fig. 39-28); however, radiolucent stones, such as uric acid stones and cystine stones, may not be visualized, and stool in the colon may make it difficult to identify smaller stones in the ureter. The test of choice at most centers for diagnosing an acute stone is a noncontrast, helical CT scan (see Fig. 39-7). All stones, regardless of composition, are visualized on CT scan with the exception of a small percentage of indinavir stones. Indinavir stones form in HIV-positive patients treated with the protease inhibitor indinavir sulfate. Urinary stones can also be diagnosed using intravenous pyelograms and renal ultrasounds (see Fig. 39-9). Both of these modalities, as well as CT scans, are well suited for evaluating the degree of hydronephrosis resulting from an obstructive stone.

Management The majority of renal stones will pass spontaneously. Only 10% of patients presenting with an acute renal stone require hospital admission. Patients with any of the following presentations should

be managed as an inpatient: intractable pain, severe nausea with inability to tolerate oral intake, urinary infection, or renal insufficiency. All other patients can be managed on an outpatient basis. Patients with urinary stones usually present for medical attention as a result of pain, making pain relief a priority. Intramuscular injections of meperidine or morphine are effective. Oral narcotics should be prescribed as necessary. Hydration should be encouraged to promote passage of the stone and patients should be instructed to filter their urine. Retrieved stones can be analyzed for chemical composition. Patients with obstructing stones and no evidence of urinary infection can safely be given up to 4 weeks to spontaneously pass their stone. No detectable renal damage occurs within 4 weeks of even complete ureteral obstruction. However, in the presence of a urinary infection, emergent intervention is indicated. A percutaneous nephrostomy tube or a ureteral stent should be placed to establish drainage of the obstructed urinary system. Following treatment of the urinary infection, the stone can be treated electively. Stones 4 to 5 mm in diameter have at least a 40 to 50% chance of passing spontaneously; however, stones greater than 6 mm in diameter have less than 5% chance of passing. Therefore, patients with larger stones should be considered for early intervention.

Surgical Management. The least-invasive treatment option for renal stones is extracorporeal shock wave lithotripsy (ESWL) (Fig. 39-29). Shock waves are generated outside the body and focused on the stone. The shock waves harmlessly propagate through intervening tissue and attain sufficient intensity to fragment the stone only when it reaches the calculus. The stone is placed in the focal point of the shock waves by using ultrasound or fluoroscopy. ESWL has a 50 to 80% overall stone-free rate when treating stones less than 3 cm. Smaller stones are associated with a higher success rate, and residual stones can be retreated. Extremely hard stones, such as cystine stones, calcium phosphate stones, and calcium oxalate monohydrate stones, are relatively resistant to fragmentation by ESWL. Endoscopic options for the surgical treatment of upper tract stone disease include retrograde ureteroscopy and percutaneous nephroscopy. Selection of the specific approach depends on the size

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Image intensifier

Patient's kidney stone

EKG Monitor

Fluoroscope x-ray tube Shock wave generator

FIG. 39-29. Extracorporeal shock wave lithotripsy. Shock waves are generated extracorporeally and are focused on the stone by the ellipsoidal reflector.

Ellipsoidal reflector

and location of the stone. For example, a large stone filling multiple renal calyces is best treated using a percutaneous approach to directly access the kidney through the flank. The scopes used through a percutaneous flank incision are shorter and larger in diameter compared to a ureteroscope. Thus, larger and more powerful instruments can be inserted through the working port to fragment the stone. A distal ureteral stone, on the other hand, is easily accessed in a retrograde fashion by ureteroscopy. The scope is inserted through the urethra, into the bladder, and up the ureter. Retrograde ureteroscopy represents a less-invasive approach when compared to percutaneous nephroscopy. Once the stone is endoscopically visualized through a nephroscope or a ureteroscope, small stones can be snared and removed with a number of specialized instruments, such as a stone basket or a three-prong grasper. Larger stones can be fragmented intracorporeally by using a variety of energies, including laser, ultrasound, or mechanical force. Energy is applied to the stone through the working port of the scope and the stone is fragmented under direct vision.

Medical Management Stone Composition If the stone is available, it should be analyzed to determine its composition. Calcium oxalate stones are the most common stones found in patients in the United States. Hypercalciuria, which can lead to urinary stone formation, can result from increased resorption of bone as a consequence of hyperparathyroidism, from primary calcium loss by the kidney, or from pathologically increased absorption of calcium in the jejunum (Table 39-3). Hyperoxaluria occurs in patients with chronic diarrhea or inflammatory bowel disease. Table 39-3 Classification of Hypercalciuria Type

Serum Calcium

Fasting Urine Calcium

Urine Calcium After Loading

Resorptive Absorptive Renal leak

Increased Normal Normal

Increased Normal Increased

Increased Increased Increased

Fatty stools in these patients result in saponification of intestinal calcium. Intestinal oxalate that is unbound to calcium is available for absorption and is eventually excreted by the kidney. An increase in urinary oxalate may also result from excess vitamin C ingestion and primary hyperoxaluria. Primary hyperoxaluria is caused by an enzymatic defect in the liver. The second most common calciumbased stones are calcium phosphate stones, which most often occur in patients with distal (type I) renal tubular acidosis. Not all urinary stones are calcium based. Struvite stones are usually composed of magnesium, ammonium, and phosphate; however, they may also be composed of carbonate apatite. Struvite stones form in alkaline urine resulting from urinary infections with nitratereducing bacteria such as Proteus, Pseudomonas, or Klebsiella species. They are usually large stones that fill multiple calyces (Fig. 39-30). Uric acid stones, on the other hand, form in acidic urine with a pH level less than 5.5. Medical therapy to alkalinize the urine will dissolve uric acid stones and can circumvent the need for surgical intervention. Pure uric acid stones are radiolucent and are associated with gout, myeloproliferative diseases, and administration of chemotherapy. Cystine stones are faintly radiopaque on plain film. They occur in patients with primary cystinuria, which is inherited as an autosomal recessive disorder. Patients with primary cystinuria also have increased urinary loss of ornithine, arginine, and lysine.

Medical Treatment Without medical treatment, more than half of all patients with a history of stone disease will have recurrent stones within 5 years.79,80 Patients with kidney stones and the following characteristics are at a high risk for recurrence and should undergo a metabolic work-up: prior history of stone disease, family history of stone disease, chronic urinary tract infections, inflammatory bowel disease, gout, bone disease, and nephrocalcinosis. The need for an extensive work-up and treatment in first-time stone formers is controversial. However, all patients with a history of stone disease should be instructed to make several lifestyle changes that reduce the risk of stone formation.81 Patients should drink enough water to produce at least 2 L of urine per day. They should limit protein and salt intake, and should not ingest excessive amounts of vitamin C. However, they should not limit calcium intake because several studies show that

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FIG. 39-30. Bilateral staghorn calculi seen on CT scan. Staghorn calculi extend into multiple calyces and are most commonly struvite stones, composed of magnesium, ammonium, and phosphate.

higher calcium diets are associated with a reduced risk of stone formation. The metabolic work-up should be performed after at least 1 month following an acute stone episode. A simple evaluation, which can be performed in all patients with a history of stone disease, includes radiologic imaging such as a CT scan or IVP, complete blood count, serum chemistries, urinalysis, and urine culture. Patients with abnormalities on this simplified evaluation, or patients at higher risk for recurrent stone disease, should be further evaluated with a 24-hour urine collection for calcium, oxalate, magnesium, phosphorus, uric acid, and creatinine. Based on the specific metabolic abnormality, directed therapy can be prescribed. However, more empiric therapy simply based on 24-hour urinary calcium appears to be equally effective. Patients with normal levels of urinary calcium can be treated with potassium citrate, which acts as an inhibitor for stone formation in the urine. Thiazide diuretics, which decrease urinary calcium excretion, can be added in patients with increased urinary calcium.

SEXUAL DYSFUNCTION Erectile Dysfunction Erectile dysfunction is defined as the inability to maintain an erection sufficient for sexual performance. The prevalence of erectile dysfunction increases with age. According to the Massachusetts Male Aging Study, which surveyed 1709 men, the prevalence of complete erectile dysfunction is approximately 5% in 40-year-old men and 15% in 70-year-old men.82 Moderate erectile dysfunction was found in 17% of 40-year-old men and 34% of 70-year-old men. Some have estimated that as many as one in four men will suffer from erectile dysfunction by the age of 65 years. Risk factors for erectile dysfunction in the general population include age, diabetes mellitus, heart disease, and hypertension. Normal erections occur in response to parasympathetic innervation received from the cavernous nerve, and involve arterial dilation and relaxation of the smooth muscles of the corpora cavernosa. The venules in the corpora cavernosa become passively compressed by the engorging sinusoids, resulting in the trapping of blood. Nitric

oxide is the major neurotransmitter responsible for erections. Nitric oxide results in increased production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are important secondary transmitters mediating relaxation of corporal smooth muscles.83 Detumescence occurs when phosphodiesterases break down cAMP and cGMP.84 Evaluation of erectile dysfunction starts with a detailed history, including medical and psychosexual history, and physical examination. Basic diagnostic tests should be obtained to assess risk factors for erectile dysfunction such as fasting glucose, glycosylated hemoglobin, lipid profile, and testosterone levels. Other diagnostic tests to consider include serum prolactin, luteinizing hormone, thyroid-stimulating hormone, complete blood count, and urinalysis. All abnormal findings should be further evaluated. For example, in patients with decreased serum testosterone, the hypothalamic– pituitary–gonadal axis should be evaluated with luteinizing hormone and follicle-stimulating hormone levels. Patients with endocrine disorders resulting in decreased testosterone levels may have decreased sexual interest; however, they do not, in general, have erectile failure. For patients with no treatable disorders identified on initial evaluation, a therapeutic trial can be offered. Oral drugs, such as sildenafil, inhibit cGMP phosphodiesterases and are effective in 60 to 70% of patients.85 These drugs are, however, contraindicated in patients with severe cardiac disease and in patients taking nitrates such nitroglycerin or amyl nitrate. Patients with erectile dysfunction resulting from neurogenic and vasogenic causes may benefit from treatment with phosphodiesterase inhibitors; however, patients who have had both cavernous nerves excised during radical retropubic prostatectomy will not respond. Such patients might respond to intracavernous injections. The most commonly used agent for intracavernous injections is prostaglandin E1 , which stimulates cAMP synthesis. Other treatment options include vacuum erection devices and surgical implantation of a penile prosthesis. For younger patients with potentially correctable causes of erectile dysfunction, or for patients who wish to know the specific etiology of their erectile dysfunction, more specialized studies can be performed. As an example, a patient with arteriogenic impotence

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caused by a focal arterial stenosis following blunt trauma is a candidate for surgical revascularization. Studies that can delineate the etiology of erectile dysfunction include further psychiatric evaluation, nocturnal penile tumescence/rigidity assessment, penile angiography, cavernosography, and neurophysiologic testing.

Peyronie’s Disease Peyronie’s disease results from a dense fibrous plaque that forms on the tunica albuginea, causing a curvature of the erect penis.86−88 Although the precise etiology of the fibrous plaque is unknown, it is believed that the plaque represents scar tissue resulting from microscopic tears of the tunica albuginea that form during intercourse. Very dense plaques may be appreciated on physical exam. However, in most patients, the flaccid penis is normal on examination and the penile curvature is only noted in the erect penis. Peyronie’s disease has an acute phase and a chronic phase. The acute phase is associated with pain and inflammation as the plaque is forming. During the acute phase, medical therapy with p-aminobenzoic acid, vitamin E, colchicines, or tamoxifen may be modestly successful. Once the pain subsides and the plaque is stable, patients with mild curvatures that do not interfere with intercourse should be observed. Surgical correction should be considered if the penile curvature interferes with sexual intercourse. Patients with Peyronie’s disease and erectile dysfunction can be treated with a penile implant. Patients with normal erection can be treated either by plicating the tunica albuginea on the outside of the Peyronie’s curvature or by grafting a patch onto the inside of the Peyronie’s curvature.

Priapism Priapism refers to an erection that is unrelated to sexual activity or persists beyond sexual activity. Priapism can be classified as lowflow (ischemic) or high-flow (nonischemic). The two forms of priapism can be distinguished by assessing the blood gas drawn from the penile corpora. The blood gas from a normal penis that is erect or a penis affected by high-flow priapism is similar to an arterial blood gas. However, in low-flow priapism, the blood gas will be similar to that of venous blood. Low-flow priapism results from venous occlusion. It is associated with severe pain. It is essentially a compartment syndrome of the penis and should be treated as a medical emergency. Most priapisms are idiopathic; however, specific causes of low-flow priapism include sickle cell disease, pelvic tumors, leukemia, spinal cord injury, penile injections for erectile dysfunction, antidepressants, and antipsychotics, especially chlorpromazine. The management of low-flow priapism should be dictated by the duration of the priapism. Within 36 hours of onset of low-flow priapism, intracorporal irrigation with an alpha-adrenergic agonist may be effective. A variety of protocols exist. One example of a protocol for intracorporal irrigation involves diluting 5 mg of phenylephrine in 500 mL of normal saline and repeatedly aspirating 20 mL of blood and injecting 20 to 30 mL of the phenylephrine solution through a 21-gauge butterfly needle. If this is ineffective, or if the priapism has been present for more than 36 hours, a distal shunt should be performed under anesthesia. A commonly performed distal shunt is the Winter shunt,89 in which a biopsy needle is inserted through the penile glans into the corpora cavernosa to create a shunt (Fig. 39-31). If this procedure is unsuccessful, a more proximal shunting procedure, between the corpora cavernosum and the corpora spongiosum, should be performed. The rationale for these shunting procedures is that the glans of the penis

FIG. 39-31. Winter shunt. A biopsy needle is inserted through the penile glans into the corpora cavernosum. A shunt is created between the corpora cavernosum, which is affected by a veno-occlusive process in priapism, and the glans, which is unaffected.

and the corporal spongiosum are flaccid during priapism and unaffected by the veno-occlusive process. Therefore, a shunt will allow the occluded blood in the corpora cavernosa to drain. Priapism resulting from sickle cell disease or leukemia should initially be managed medically. Patients with sickle cell disease tend to have recurrence of priapism, and, therefore, a trial of conservative therapy directed at preventing additional sickling is warranted. Medical therapy should include hydration, oxygenation, and alkalinization. Transfusions or exchange transfusions should be considered. Patients with leukemia should be promptly treated with chemotherapy rather than surgery. High-flow priapism is generally painless, and because tissue ischemia is not a feature, treatment is less urgent. Nonischemic priapism results from an arterial-venous fistula that is most commonly secondary to trauma. The diagnosis of high-flow priapism can be confirmed by color Doppler ultrasound. The arterial-venous fistula can be identified by angiography and selectively embolized. If this fails, the fistula can be surgically ligated.

Infertility Approximately 15% of couples are unable to conceive within 1 year.90−92 Of couples treated for infertility, approximately 20% of cases are a result of a male factor and 30 to 40% of cases are a result of a combination of male and female factors. It is important to keep in mind that 1% of men being evaluated for infertility have a serious underlying medical condition, such as testicular cancer. The initial evaluation should start with a thorough reproductive and sexual history. Couples trying to conceive should ideally have intercourse every other day, starting about 6 days before the predicted date of ovulation. Medications that have antiandrogen effects (i.e., spironolactone, ketoconazole, cimetidine, and tetracycline) or that impair spermatogenesis (i.e., tetracycline, erythromycin, and nitrofurantoin) should be stopped. Many commercial lotions and lubrications impair sperm motility and should not be used during intercourse. It is also important to keep in mind that spermatogenesis may be impaired for up to 3 months following a febrile illness. During the physical exam the patient should be assessed for signs of abnormalities associated with infertility. Gynecomastia may be a sign of an endocrine disorder. Eunuchoid body habitus may suggest Klinefelter’s syndrome. The scrotal contents should be carefully examined. The normal testicular volume in white men is 20 mL or approximately 4 × 3 cm. The vas deferens is absent in cystic fibrosis. The spermatic cord should be examined with and without a Valsalva maneuver for presence of varicoceles. Clinically detected varicoceles are the most common abnormality in men treated for infertility, and surgical repair leads to improved semen quality in approximately two-thirds of patients, doubling the chances of

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FIG. 39-32. Renal ultrasound in a newborn demonstrating significant hydronephrosis.

conception. However, there is no evidence that repair of subclinical varicoceles detected on ultrasound or venography improves pregnancy rates. The next step in the evaluation is a semen analysis. The specimen should be obtained following at least 3 days of abstinence and examined within 1 to 2 hours of collection. At least two specimens collected several weeks apart should be examined. The ejaculate is evaluated for volume, sperm count, and motility and morphology of the sperm. Low ejaculatory volume may be caused by retrograde ejaculation into the bladder or obstruction of the vas deferens. The hypothalamic-pituitary axis should be evaluated in patients with oligospermia (less than 5 to 10 million sperm/mL); men with primary hypogonadism should undergo chromosomal study. Patients who are azoospermic or who have severe oligospermia may have testicular failure or obstructed vas deferens. Further work-up following a semen analysis might include a vasogram and testicular biopsy. A vasogram will detect strictures

A

B

FIG. 39-33. A . Hydronephrosis resulting from a ureteropelvic junction obstruction. B . Site of stenosis (arrow).

FIG. 39-34. Voiding cystourethrogram. This VCUG in an infant demonstrates grade IV ureteral reflux on the left.

of the vas deferens and ejaculatory duct. At the time of testicular biopsy, sperm can be retrieved for use with assisted reproductive techniques. During the evaluation of the male partner, all correctible causes of infertility should be identified and treated. If treatment is not possible or the treatment is unsuccessful, assisted reproductive techniques such as intracytoplasmic sperm injection can be tried with a 20 to 30% success rate per cycle.

FIG. 39-35. The grading system adopted by the International Reflux Study in Children. The urinary system is represented in brown. (Reproduced with permission from Arant BS Jr: Vesicoureteral reflux and renal injury. Am J Kidney Dis 10:491, 1991.)

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A

B

PEDIATRIC UROLOGY Hydronephrosis Hydronephrosis, or dilation of the upper urinary tract, may signify a congenital anomaly with the potential for adversely impacting renal function. Fetal hydronephrosis is diagnosed in 1 of 500 routine prenatal ultrasounds.93 The majority of fetal hydronephrosis resolves by birth or within the first year of life. Fetal intervention is rarely necessary, and should only be considered in cases of bilateral hydronephrosis and severe oligohydramnios. Following birth,

FIG. 39-36. Ureterocele. A . Left ureterocele (arrow). B . Bilateral ureteroceles (arrows).

severe hydronephrosis may be appreciated as a palpable abdominal mass. In cases of bilateral hydronephrosis, a renal ultrasound (Fig. 39-32) and a VCUG should be obtained shortly after birth. For unilateral hydronephrosis, both studies can be obtained electively at approximately 1 month of life. Because neonates with hydronephrosis are at a higher risk for pyelonephritis, all neonates diagnosed with unilateral or bilateral hydronephrosis should be started on antibiotic prophylaxis (i.e., amoxicillin, 10 mg/kg per 24 hours). Pyelonephritis during the first year of life, when the

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CLASSIFICATION OF HYPOSPADIAS

GLANULAR

ANTERIOR 65%

CORONAL ANT. PENILE

MIDDLE 15%

MIDSHAFT

POST. PENILE PENOSCROTAL

POSTERIOR 20% SCROTAL

PERINEAL

FIG. 39-38. Classification of hypospadias and frequency by location of hypospadias.

FIG. 39-37. Posterior urethral valve. The urethral is seen bulging proximal to the urethral valve. Bilateral ureteral reflux is seen in this voiding cystourethrogram (VCUG).

kidney is still immature, leads to permanent deterioration in renal function.

prophylaxis. The most commonly performed surgical repair is a dismembered pyeloplasty. The dyskinetic segment of the collecting system at the UPJ is resected, and the ureter and renal pelvis are brought over any crossing vessels that may be present and then anastomosed. The ureter in older patients may readily accommodate endoscopic instruments and a UPJ obstruction may be incised using either a percutaneous or a ureteroscopic approach. Kidneys with minimal function may best be treated with a simple nephrectomy.

Ureteropelvic Junction Obstruction Ureteropelvic junction (UPJ) obstruction is the most common cause of hydronephrosis in neonates (Fig. 39-33). The precise etiology is poorly defined. UPJ obstructions may result from abnormal development of the smooth muscle at the UPJ. In some cases, an aberrant lower pole vessel crosses the UPJ, possibly resulting in extrinsic compression. Most neonates are asymptomatic, while older children present with symptoms, such as flank or abdominal pain. Initial evaluation should include a renal ultrasound and a VCUG to rule out coexisting reflux. If a UPJ obstruction is suspected, a nuclear renal scan should be performed to assess differential function in the right and left kidneys, and to assess renal pelvic drainage by timing the washout of nuclear isotope following Lasix administration (see Fig. 39-11). Mild to moderate hydronephrosis resulting from a UPJ obstruction can be safely observed and will usually resolve by 2 years of age. Antibiotic prophylaxis should be continued until the UPJ obstruction resolves completely. Surgical repair should be performed for a UPJ obstruction associated with severe hydronephrosis, diminished renal function, highgrade obstruction or breakthrough infections while on antibiotic

Vesicoureteral Reflux Vesicoureteral reflux is the second most common cause of hydronephrosis and may be found in as many as 70% of infants presenting with a urinary tract infection.94−97 For vesicoureteral reflux detected after birth, there is a female preponderance, with 85% of cases diagnosed in females. Vesicoureteral reflux is often an inherited anomaly. It is ten times more common in whites than in blacks and up to 45% of siblings of children with reflux also have reflux.98 Primary reflux is a congenital anomaly caused by a deficiency of the longitudinal bladder muscle surrounding the intramural portion of the ureter. Secondary reflux results from bladder outlet obstruction and an increase in intravesical pressure. Secondary reflux is corrected by addressing the underlying bladder outlet obstruction. Infants with hydronephrosis on prenatal ultrasound, history of a urinary tract infection, or siblings diagnosed with reflux should be evaluated for primary reflux. Vesicoureteral reflux is diagnosed by demonstrating ureteral reflux on VCUG (Fig. 39-34). The degree of reflux can be graded according to the International Classification

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Relaxing incision through the urethral plate

Urethral opening

A

Urethral opening

B

Catheter

C

FIG. 39-39. Tabularized incised plate urethroplasty. A and B . The two critical steps to this procedure involve a “relaxing” incision of the urethral plate distal to the hypospadias opening and (C , D ) tubularization of the “relaxed” urethral plate.

D

System devised in 1981 by the International Reflux Study Committee (Fig. 39-35). As the infant bladder grows and the bladder wall thickens, most low-grade refluxes resolve.99,100 Approximately 85% of all grades I and II reflux will spontaneously resolve, while 30 to 40% of grades III and IV reflux and 9% of grade V reflux will resolve. Given that some high-grade reflux will eventually resolve, it is reasonable to conservatively follow children with reflux, regardless of the grade. However, it is critical that patients managed conservatively are maintained on antibiotic prophylaxis. Surgical repair should be performed in all patients with a breakthrough infection while on antibiotic prophylaxis. Although there is some controversy surrounding this issue, most practitioners recommend surgical correction before the onset of puberty for girls with persistent reflux. The rationale for this recommendation is based on the reasoning that after the cessation of longitudinal growth, the likelihood of spontaneous resolution of reflux is small, and during pregnancy, reflux places women at a higher risk of pyelonephritis and miscarriage. Boys are at a lower risk of infection secondary to reflux. Therefore, most practitioners recommend stopping antibiotic prophylaxis after early childhood and continuing to observe persistent reflux. The gold standard for intervention is an open surgical reimplant of the ureter into the bladder. Another option involves cystoscopically injecting a bulking agent, such as collagen or a synthetic material. The bulking agent is injected submucosally with the

goal of increasing resistance at the ureteral orifice and preventing reflux.

Ureterocele A ureterocele is a cystic dilation of the distal ureter associated with a stenotic ureteral opening (Fig. 39-36).101−106 Ureteroceles occur four times more frequently in girls than in boys and occur almost exclusively in whites. Approximately 80% are associated with the upper-pole moiety of a duplicated ureter. If a duplicated urinary collection system is present, the upper-pole ureter inserts more caudally and medially in relation to the lower-pole ureter. Ureteroceles with the orifice in the bladder trigone are considered orthotopic, while ureteroceles with the orifice distal to the bladder neck are considered ectopic. The majority of neonatal ureteroceles are diagnosed postnatally during work-up prompted by prenatal hydronephrosis. After birth, the ureterocele can be seen on both ultrasound and VCUG. A VCUG is performed to better localize the ureterocele and evaluate for reflux. It is not uncommon for a ureterocele to distort the bladder and produce ureteral reflux in the contralateral ureter or the ipsilateral lower pole moiety of a duplicated ureter. The findings associated with a ureterocele vary based on the location of the ureterocele and size of the ureteral opening. If a duplicated ureter is present, 65% of the ureters to the lower-pole

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A

C

kidney will reflux. An orthotopic ureterocele usually produces ipsilateral hydronephrosis; however, a large, orthotopic ureterocele may obstruct the contralateral ureter and produce bilateral hydronephrosis. An ectopic ureterocele can obstruct the urethra, resulting in bladder outlet obstruction and may also produce bilateral hydronephrosis. Ureteroceles associated with a single collecting system are generally less obstructive and usually found incidentally in adult patients. These ureteroceles in adults rarely require intervention. In the pediatric population, the treatment depends on the clinical presentation. It is not uncommon for infants with undiagnosed ureteroceles to present with urosepsis. Such patients need to be emergently treated by endoscopically incising the ureterocele and establishing ureteral drainage. Uninfected neonates can be electively treated with endoscopic incision. Following this procedure, approximately 25% will develop reflux and may require a secondary procedure, such as ureteral reimplantation. Infants presenting after 1 year of age with a ureterocele will have had long-standing obstruction and are less likely to have functioning renal tissue draining into the affected ureter. Treatment for such patients should be individualized, and reconstructive procedures should be performed with the goal of establishing drainage, preventing reflux and decreasing risk of future urinary infections.

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B

FIG. 39-40. Testicular torsion. A . In intravaginal torsion, the tunica vaginalis is opened to demonstrate the torsion. B . In extravaginal torsion, both layers of the tunica vaginalis twist with the cord. C . Torsion of the appendix testis.

Posterior Urethral Valve Posterior urethral valves are obstructive urethra lesions usually diagnosed in male newborns and infants. The valves are thin, membranous folds located in the prostatic urethra. Posterior urethra valves are the most common cause of bilateral hydronephrosis detected on prenatal ultrasound. The test of choice to confirm the diagnosis following birth is a VCUG (Fig. 39-37). Older children with undiagnosed posterior urethral valve often present with urinary incontinence. The first step in treatment involves endoscopic ablation of the valve. A Foley catheter should be placed in the bladder until the procedure can be performed. Depending on the degree of obstruction, patients with posterior valves are at high risk of renal failure, and renal function should be closely monitored.

The Penis Hypospadias Hypospadias results from incomplete fusion of the urethral plate during development of the male penis. Hypospadias occurs in one in 300 males. The risk for hypospadias is increased by history of maternal estrogen or progestin use during pregnancy. Hypospadias are classified by the location of the urethral opening (Fig. 39-38).

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Approximately 70% of hypospadias occur on the corona or distal shaft of the penis. Neonates with a hypospadias are not at increased risk for having other congenital abnormalities of the urinary tract. However, penoscrotal or perineal hypospadias may represent an intersex disorder and evaluation should include a karyotype. An intersex work-up is also indicated if a hypospadias and an undescended testicle are noted. For psychologic reasons, the hypospadias should be repaired before 2 years of age. Newborns diagnosed with a hypospadias should not be circumcised. The foreskin may be needed for future corrective surgery. The goals of surgical treatment include correction of any penile curvature, moving the urethral opening to the tip of the glans, and producing a cosmetically satisfactory result. A very effective procedure for correction of distal hypospadias is tabularized incised plate urethroplasty (Fig. 39-39). The two critical steps to this procedure involve a “relaxing” incision of the urethral plate distal to the hypospadias opening and tubularization of the “relaxed” urethral plate. Repair of more proximal hypospadias defects may require use of skin grafts. For example, the penile skin or the foreskin can be mobilized on a pedicle of dartos fascia and used either as an onlay or a tubularized graft.

Phimosis Phimosis is the inability to retract the foreskin past the glans of the penis. In most neonates, a physiologic phimosis exists. By 3 years of age, 90% of males are able to retract their foreskin. Forceful retraction of the foreskin is not recommended. If a phimosis continues to exist at 4 or 5 years of age, a topical corticosteroid cream can be applied to the foreskin three to four times daily for 6 weeks.107 This will allow the foreskin to be easily retracted in approximately two-thirds of cases. If the phimosis is resistant to topical steroid therapy, or if the patient requires treatment for balanitis, circumcision should be considered.

Paraphimosis

obliquely on the cord. As a result, the testicle has a horizontal lie when the patient is standing. It is believed that contraction of the cremasteric muscle initiates the characteristic rotation seen in torsion. From the examining physician’s perspective, the patient’s left testicle rotates counterclockwise and the right testicle rotates clockwise. Adolescents presenting with testicular torsion complain of severe pain. The differential diagnosis includes epididymo-orchitis and torsion of the appendix testis. Epididymo-orchitis is rare in adolescents and is accompanied by pyuria. Torsion of the appendix testis produces a more focal area of pain and often a bluish discoloration can be appreciated in the scrotum over the testicular appendage. When evaluating a patient with torsion, manual detorsion can be attempted. If this fails, the patient should be immediately taken to the operating room. Surgery performed within 4 to 6 hours of onset of pain has better than a 90% testicular salvage rate. Therefore, unless the evidence for a competing diagnosis is overwhelming, surgery should not be delayed by diagnostic studies. At the time of surgery, an orchiopexy should be performed by fixing the testicle to the scrotal wall at three different points. The anatomic predisposition to torsion affects both testicles; therefore, the contralateral testicle should be similarly repaired. In select cases where the diagnosis is uncertain and testicular torsion is unlikely, Doppler ultrasound or nuclear scintigraphy can be performed to more definitively rule out testicular torsion.

A B

Paraphimosis occurs when the foreskin that has been retracted past the glans of the penis cannot be reduced to its normal position. Constriction of the distal penis by the foreskin leads to venous congestion and swelling, making reduction of the foreskin even more difficult. As swelling and edema worsen, arterial supply to the glans may be compromised, resulting in ischemia, and even necrosis of the glans. Paraphimosis should be reduced emergently. A variety of techniques have been described. However, in most cases, simply squeezing the glans to reduce the swelling and forcefully reducing the foreskin is successful.

The Testicle

D C

Testicular Torsion Testicular torsion occurs when the testicle rotates and strangulates its blood supply at the level of the spermatic cord. Testicular torsion is a medical emergency that requires prompt surgical attention. Torsion occurring in the neonatal and prenatal period is extravaginal—the testicle and both layers of the tunica vaginalis rotate. Testicular torsion in neonates may not produce symptoms and is usually only noted after the testicle has atrophied. Torsion in children and young adults is intravaginal—the testicle and the inner layer of the tunica vaginalis rotate (Fig. 39-40). Intravaginal torsion is most common in 12- to 18-year-olds, with peak incidence at age 13 years. In patients at risk for intravaginal torsion, the tunica attaches higher up on the spermatic cord (bell clapper deformity) and the cremasteric muscle inserts

E FIG. 39-41. Differential diagnosis of scrotal fluid collections. A . Normal. B . Communicating hydrocele. C . Noncommunicating hydrocele. D . Noncommunicating inguinal hydrocele. E . Hernia.

39/UROLOGY

Hydrocele In infants, hydroceles are fluid collections within the tunica vaginalis or processus vaginalis (Fig. 39-41). During development, the testicles are enveloped by a double layer of peritoneum, which becomes the tunica vaginalis. With normal development, the processus vaginalis, which connects the tunica vaginalis with the peritoneum, becomes obliterated. If the process vaginalis persists, peritoneal fluid can track into the space surrounding the testicles, creating a communicating hydrocele. If bowel tracks down the same space, an indirect inguinal hernia is the result. If the processus vaginalis obliterates and traps fluid in the tunica vaginalis, a noncommunicating hydrocele is the result. Surgical repair is reserved for tense hydroceles that may interfere with testicular circulation or large hydroceles that may cause discomfort. Communicating hydroceles in newborns should generally be observed. Spontaneous closure of the processus vaginalis and resolution of the hydrocele is common; however, hydroceles that persist beyond the first year of life are unlikely to resolve. In pediatric patients, the surgery should be performed through an inguinal incision. The processus vaginalis should be ligated and the distal hydrocele sac should be excised. In adults, hydroceles most commonly form as a consequence of local inflammation and the process vaginalis is almost never patent. Consequently, surgery is performed through a scrotal incision. The hydrocele sac is decompressed and then either plicated or excised to prevent recurrence. References 1. Walsh PC, Retik AB, Vaughan ED, et al (eds): Campbell’s Urology, 8th ed. Philadelphia: W.B. Saunders, 2002. 2. Tanagho EA, McAninch JW (eds): Smith’s General Urology, 16th ed. New York: McGraw-Hill, 2003. 3. Marshall FF (eds): Textbook of Operative Urology. Philadelphia: W.B. Saunders, 1996. 4. Berry SJ, Coffey DS, Walsh PC, et al: The development of human benign prostatic hyperplasia with age. J Urol 132:474, 1984. 5. Bosch JL, Kranse R, van Mastrigt R, et al: Reasons for the weak correlation between prostate volume and urethral resistance parameters in patients with prostatism. J Urol 153:689, 1995. 6. Steele GS, Sullivan MP, Sleep DJ, et al: Combination of symptom score, flow rate and prostate volume for predicting bladder outflow obstruction in men with lower urinary tract symptoms. J Urol 164:344, 2000. 7. O’Leary MP, Barry MJ, Fowler FJ Jr.: Hard measures of subjective outcomes: Validating symptom indexes in urology. J Urol 148:1546, 1992. 8. McConnell JD, Barry MJ, Bruskewitz RC, et al: Benign Prostatic Hyperplasia: Diagnosis and Treatment. Clinical Practice Guideline, No. 8. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. 1994. 9. Shapiro E, Hartanto V, Lepor H: The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle. Prostate 21:297, 1992. 10. Djavan B, Marberger M: A meta-analysis on the efficacy and tolerability of alpha1 -adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 36:1, 1999. 11. Lepor H: Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group. Urology 51:892, 1998. 12. Marks LS, Partin AW, Epstein JI, et al: Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. J Urol 163:1451, 2000.

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13. Marberger MJ: Long-term effects of finasteride in patients with benign prostatic hyperplasia: A double-blind, placebo-controlled, multicenter study. PROWESS Study Group. Urology 51:677, 1998. 14. Pomer S, Dobrowoloski ZF: The therapy of benign prostatic hyperplasia using less-invasive procedures: The current situation. BJU Int 89:773, 2002. 15. Jemal A, Murray T, Samuels A, et al: Cancer statistics, 2003. CA Cancer J Clin 53:5, 2003. 16. Pantuck AJ, Zisman A, Belldegrun AS: The changing natural history of renal cell carcinoma. J Urol 166:1611, 2001. 17. Tsui KH, Shvarts O, Smith RB, et al: Renal cell carcinoma: Prognostic significance of incidentally detected tumors. J Urol 163:426, 2000. 18. Gnarra JR, Tory K, Weng Y, et al: Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7:85, 1994. 19. Zbar B, Tory K, Merino M, et al: Hereditary papillary renal cell carcinoma. J Urol 151:561, 1994. 20. Uzzo RG, Novick AC: Nephron sparing surgery for renal tumors: Indications, techniques and outcomes. J Urol 166:6, 2001. 21. Gill IS, Novick AC, Meraney AM, et al: Laparoscopic renal cryoablation in 32 patients. Urology 56:748, 2000. 22. Mickisch GH, Garin A, van Poppel H, et al: Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: A randomised trial. Lancet 358:966, 2001. 23. Flanigan RC, Salmon SE, Blumenstein BA, et al: Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655, 2001. 24. Figlin RA: Renal cell carcinoma: Management of advanced disease. J Urol 161:381, 1999. 25. Fisher RI, Rosenberg SA, Fyfe G: Long-term survival update for highdose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 6(Suppl 1):S55, 2000. 26. Cohen SM, Johansson SL: Epidemiology and etiology of bladder cancer. Urol Clin North Am 19:421, 1992. 27. Johansson SL, Cohen SM: Epidemiology and etiology of bladder cancer. Semin Surg Oncol 13:291, 1997. 28. Varkarakis MJ, Gaeta J, Moore RH, et al: Superficial bladder tumor. Aspects of clinical progression. Urology 4:414, 1974. 29. Lokeshwar VB, Soloway MS: Current bladder tumor tests: Does their projected utility fulfill clinical necessity? J Urol 165:1067, 2001. 30. Kaye KW, Lange PH: Mode of presentation of invasive bladder cancer: Reassessment of the problem. J Urol 128:31, 1982. 31. Lerner SP, Skinner DG, Lieskovsky G, et al: The rationale for en bloc pelvic lymph node dissection for bladder cancer patients with nodal metastases: Long-term results. J Urol 149:758, 1993. 32. Stein JP, Cai J, Groshen S, et al: Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: Concept of lymph node density. J Urol 170:35, 2003. 33. Lutzeyer W, Rubben H, Dahm H: Prognostic parameters in superficial bladder cancer: An analysis of 315 cases. J Urol 127:250, 1982. 34. Carroll P (ed): Urothelial Carcinoma Cancers of the Bladder Ureter and Renal Pelvis, 14th ed. Norwalk, CT: Appleton and Lange, 1995. 35. Malmstrom PU, Wijkstrom H, Lundholm C, et al: 5-Year follow-up of a randomized prospective study comparing mitomycin C and bacillus Calmette-Gu´erin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group. J Urol 161:1124, 1999. 36. Schoenberg M: Management of invasive and metastatic bladder cancer, in Walsh PC, Retik AB, Vaughan ED, et al (eds): Campbell’s Urology, 8th ed. Philadelphia: W.B. Saunders, 2002, p. 2803. 37. Kim HL, Steinberg GD: The current status of bladder preservation in the treatment of muscle invasive bladder cancer. J Urol 164:627, 2000. 38. Carter BS, Bova GS, Beaty TH, et al: Hereditary prostate cancer: Epidemiologic and clinical features. J Urol 150:797, 1993. 39. Kim HL, Steinberg GD: New insights and candidate genes and their implications for care of patients with hereditary prostate cancer. Curr Urol Rep 1:9, 2000.

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40. Moyad MA: Selenium and vitamin E supplements for prostate cancer: Evidence or embellishment? Urology 59:9, 2002. 41. Kim HL, Benson DA, Stern SD, et al: Practice trends in the management of prostate disease by family practice physicians and general internists: An Internet-based survey. Urology 59:266, 2002. 42. Walsh PC, Marschke P, Ricker D, et al: Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 55:58, 2000. 43. Catalona WJ, Carvalhal GF, Mager DE, et al: Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies. J Urol 162:433, 1999. 44. Prow DM: Germ cell tumors: Staging, prognosis, and outcome. Semin Urol Oncol 16:82, 1998. 45. Donohue JP: Selecting initial therapy. Seminoma and nonseminoma. Cancer 60:490, 1987. 46. Warde P, Jewett MA: Surveillance for stage I testicular seminoma. Is it a good option? Urol Clin North Am 25:425, 1998. 47. Shahidi M, Norman AR, Dearnaley DP, et al: Late recurrence in 1263 men with testicular germ cell tumors: Multivariate analysis of risk factors and implications for management. Cancer 95:520, 2002. 48. Cabanas RM: An approach for the treatment of penile carcinoma. Cancer 39:456, 1977. 49. McDougal WS, Kirchner FK Jr., Edwards RH, et al: Treatment of carcinoma of the penis: The case for primary lymphadenectomy. J Urol 136:38, 1986. 50. Culkin DJ, Beer TM: Advanced penile carcinoma. J Urol 170:359, 2003. 51. Jacobson SH, Kallenius G, Lins LE, et al: P-fimbriae receptors in patients with chronic pyelonephritis. J Urol 139:900, 1988. 52. Stamm WE, Raz R: Factors contributing to susceptibility of postmenopausal women to recurrent urinary tract infections. Clin Infect Dis 28:723, 1999. 53. Dalla Palma L, Pozzi-Mucelli F, Ene V: Medical treatment of renal and perirenal abscesses: CT evaluation. Clin Radiol 54:792, 1999. 54. Rathod KR, Narlawar RS, Garg A, et al: Percutaneous conservative management of emphysematous pyelonephritis. J Postgrad Med 47:66, 2001. 55. Smellie JM: Urinary tract infection, vesicoureteric reflux, and renal scarring. Semin Urol 4:82, 1986. 56. Wainstein MA, Graham RC Jr., Resnick MI: Predisposing factors of systemic fungal infections of the genitourinary tract. J Urol 154:160, 1995. 57. Wise GJ, Kozinn PJ, Goldberg P: Amphotericin B as a urologic irrigant in the management of noninvasive candiduria. J Urol 128:82, 1982. 58. Kauffman CA, Vazquez JA, Sobel JD, et al: Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis 30:14, 2000. 59. Drach GW, Fair WR, Meares EM, et al: Classification of benign diseases associated with prostatic pain: Prostatitis or prostatodynia? J Urol 120:266, 1978. 60. Wagner TH, Hu TW: Economic costs of urinary incontinence in 1995. Urology 51:355, 1998. 61. Schafer W, Abrams P, Liao L, et al: Good urodynamic practices: Uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn 21:261, 2002. 62. Dupont MC, Albo ME, Raz S: Diagnosis of stress urinary incontinence. An overview. Urol Clin North Am 23:407, 1996. 63. Carey MP, Dwyer PL: Position and mobility of the urethrovesical junction in continent and in stress incontinent women before and after successful surgery. Aust N Z J Obstet Gynaecol 31:279, 1991. 64. Groutz A, Gordon D, Keidar R, et al: Stress urinary incontinence: Prevalence among nulliparous compared with primiparous and grand multiparous premenopausal women. Neurourol Urodyn 18:419, 1999.

65. Snooks SJ, Setchell M, Swash M, et al: Injury to innervation of pelvic floor sphincter musculature in childbirth. Lancet 2:546, 1984. 66. Govier FE, Kobashi K: Pubovaginal slings: A review of the technical variables. Curr Opin Urol 11:405, 2001. 67. Symmonds RE: Incontinence: Vesical and urethral fistulas. Clin Obstet Gynecol 27:499, 1984. 68. Carroll PR, McAninch JW: Operative indications in penetrating renal trauma. J Trauma 25:587, 1985. 69. Cass AS: Renovascular injuries from external trauma. Diagnosis, treatment, and outcome. Urol Clin North Am 16:213, 1989. 70. Santucci RA, McAninch JW: Diagnosis and management of renal trauma: Past, present, and future. J Am Coll Surg 191:443, 2000. 71. Matthews LA, Smith EM, Spirnak JP: Nonoperative treatment of major blunt renal lacerations with urinary extravasation. J Urol 157:2056, 1997. 72. Husmann DA, Gilling PJ, Perry MO, et al: Major renal lacerations with a devitalized fragment following blunt abdominal trauma: A comparison between nonoperative (expectant) versus surgical management. J Urol 150:1774, 1993. 73. Cass AS, Luxenberg M: Features of 164 bladder ruptures. J Urol 138:743, 1987. 74. Cass AS: The multiple injured patient with bladder trauma. J Trauma 24:731, 1984. 75. Mayher BE, Guyton JL, Gingrich JR: Impact of urethral injury management on the treatment and outcome of concurrent pelvic fractures. Urology 57:439, 2001. 76. Moudouni SM, Patard JJ, Manunta A, et al: Early endoscopic realignment of post-traumatic posterior urethral disruption. Urology 57:628, 2001. 77. Johnson CM, Wilson DM, O’Fallon WM, et al: Renal stone epidemiology: A 25-year study in Rochester, Minnesota. Kidney Int 16:624, 1979. 78. Marshall V, White RH, De Saintonge MC, et al: The natural history of renal and ureteric calculi. Br J Urol 47:117, 1975. 79. Bek-Jensen H, Tiselius HG: Stone formation and urine composition in calcium stone formers without medical treatment. Eur Urol 16:144, 1989. 80. Zerwekh JE, Reed-Gitomer BY, Pak CY: Pathogenesis of hypercalciuric nephrolithiasis. Endocrinol Metab Clin North Am 31:869, 2002. 81. Coe FL, Parks JH, Asplin JR: The pathogenesis and treatment of kidney stones. N Engl J Med 327:1141, 1992. 82. Johannes CB, Araujo AB, Feldman HA, et al: Incidence of erectile dysfunction in men 40 to 69 years old: Longitudinal results from the Massachusetts male aging study. J Urol 163:460, 2000. 83. Ignarro LJ, Bush PA, Buga GM, et al: Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170:843, 1990. 84. Soderling SH, Bayuga SJ, Beavo JA: Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem 273:15553, 1998. 85. Montorsi F, Salonia A, Deho F, et al: Pharmacological management of erectile dysfunction. BJU Int 91:446, 2003. 86. Davis CJ Jr.: The microscopic pathology of Peyronie’s disease. J Urol 157:282, 1997. 87. Brock G, Hsu GL, Nunes L, et al: The anatomy of the tunica albuginea in the normal penis and Peyronie’s disease. J Urol 157:276, 1997. 88. Gholami SS, Gonzalez-Cadavid NF, Lin CS, et al: Peyronie’s disease: A review. J Urol 169:1234, 2003. 89. Winter CC: Cure of idiopathic priapism: New procedure for creating fistula between glans penis and corpora cavernosa. Urology 8:389, 1976. 90. Spira A: Epidemiology of human reproduction. Hum Reprod 1:111, 1986. 91. Thonneau P, Marchand S, Tallec A, et al: Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988–1989). Hum Reprod 6:811, 1991.

39/UROLOGY 92. Niederberger CS: Understanding the epidemiology of fertility treatments. Urol Clin North Am 29:829, 2002. 93. Helin I, Persson PH: Prenatal diagnosis of urinary tract abnormalities by ultrasound. Pediatrics 78:879, 1986. 94. Smellie JM, Normand C: Reflux nephropathy in childhood, in KincaidSmith P (ed): Reflux Nephropathy. New York: Masson Publishing, 1979, p. 14. 95. Scott JE, Stansfeld JM: Ureteric reflux and kidney scarring in children. Arch Dis Child 43:468, 1968. 96. Smellie JM, Normand IC: Clinical features and significance of urinary tract infection in children. Proc R Soc Med 59:415, 1966. 97. Mor Y, Leibovitch I, Zalts R, et al: Analysis of the long-term outcome of surgically corrected vesico-ureteric reflux. BJU Int 92:97, 2003. 98. Noe HN: The long-term results of prospective sibling reflux screening. J Urol 148:1739, 1992. 99. Edwards D, Normand IC, Prescod N, et al: Disappearance of vesicoureteric reflux during long-term prophylaxis of urinary tract infection in children. Br Med J 2:285, 1977.

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100. Medical versus surgical treatment of primary vesicoureteral reflux: Report of the International Reflux Study Committee. Pediatrics 67:392, 1981. 101. Monfort G, Guys JM, Coquet M, et al: Surgical management of duplex ureteroceles. J Pediatr Surg 27:634, 1992. 102. Mandell J, Blyth BR, Peters CA, et al: Structural genitourinary defects detected in utero. Radiology 178:193, 1991. 103. Rickwood AM, Reiner I, Jones M, et al: Current management of duplex-system ureteroceles: Experience with 41 patients. Br J Urol 70:196, 1992. 104. Shekarriz B, Upadhyay J, Fleming P, et al: Long-term outcome based on the initial surgical approach to ureterocele. J Urol 162:1072, 1999. 105. Cooper CS, Andrews JI, Hansen WF, et al: Antenatal hydronephrosis: Evaluation and outcome. Curr Urol Rep 3:131, 2002. 106. Coplen DE: Management of the neonatal ureterocele. Curr Urol Rep 2:102, 2001. 107. Monsour MA, Rabinovitch HH, Dean GE: Medical management of phimosis in children: Our experience with topical steroids. J Urol 162:1162, 1999.

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CHAPTER

40

Gynecology Gregory P. Sutton, Robert E. Rogers, William W. Hurd, and Martina F. Mutone

External Genitalia (Vulva) Musculature of the Pelvic Floor Internal Genitalia

Uterosacral Ligament Suspension Colpocleisis Abdominal Procedures Sacral Colpopexy

Diagnosis

Surgery For Stress Urinary Incontinence

Gynecologic History Physical Examination Diagnostic Procedures Cervical Cytology Office Tissue Biopsy Vaginal Discharge Cultures Pregnancy Tests Abnormal Bleeding Bleeding Associated with Pregnancy Dysfunctional Uterine Bleeding Trauma Bleeding Secondary to Neoplasm Bleeding from Infection Bleeding of a Nongenital Etiology Pain Pelvic Mass

Needle Suspension Retropubic Colposuspension Marshall-Marchetti-Krantz (MMK) Procedure Burch Procedure Suburethral Sling Tensionless Sling Collagen Surgical Complications

Anatomy

Infections Vulvar and Vaginal Infections Mycotic Infection Parasitic Infections Bacterial Infections Viral Infections Pelvic Inflammatory Disease Treatment Surgical Therapy Endometriosis Treatment Ectopic Pregnancy Treatment Laparoscopic Procedures Abdominal Operation Medical Therapy Pelvic Floor Dysfunction Pelvic Organ Prolapse Urinary Incontinence Surgery For Pelvic Organ Prolapse Vaginal Procedures Colporrhaphy Sacrospinous Fixation

Benign Tumors Ovarian Tumors Nonneoplastic Cysts Nonfunctioning Tumors Functioning Tumors Uterine Tumors Leiomyomas Adenomyosis Polyps Cervical Lesions Vulvar Lesions Malignant Tumors Ovarian Tumors Ovarian Carcinoma Tumors of Low Malignant Potential Germ Cell Tumors Carcinoma of the Cervix Staging Treatment Endometrial Cancer Treatment Vulvar Cancer Treatment Uncommon Vulvar Tumors Gynecologic Operations Dilatation and Curettage Endoscopic Surgery Laparoscopy Hysteroscopy Abdominal Procedures Incisions Hysterectomy for Benign Disease Myomectomy

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Radical Hysterectomy (Modified from Okabayashi) Resection of Ovarian Cancer Vaginal Procedures Hysterectomy Pessaries Injuries Associated with Pelvic Surgery

Ischiocavernosus muscle

Symphysis pubis Clitoris (glans) Urethral orifice

Bulbocavernosus muscle

Vaginal orifice

Inferior fascia urogenital diaphragm

ANATOMY External Genitalia (Vulva)

Superficial transverse perineal muscle

Ischial tuberosity

The vulva is bounded by the symphysis pubis anteriorly, the anal sphincter posteriorly, and the ischial tuberosities laterally (Fig. 40-1). The labia majora form the cutaneous boundaries of the lateral vulva and represent the female homologue of the male scrotum. The labia majora are fatty folds covered by hair-bearing skin in the adult. They fuse anteriorly with the anterior prominence of the symphysis pubis, the mons veneris. Posteriorly, the labia majora meet in a structure that blends with the perineal body and is referred to as the posterior commissure. Adjacent and medial to the labia majora are the labia minora, smaller folds of connective tissue covered laterally by non-hairbearing skin and medially by vaginal mucosa. The anterior fusion of the labia minora forms the prepuce of the clitoris; posteriorly, the labia minora fuse in the fossa navicularis, or posterior fourchette. The term vestibule refers to the area medial to the labia minora bounded by the fossa navicularis and the clitoris. Both the urethra and the vagina open into the vestibule. The clitoris lies superior to the urethral meatus; the male homologue is the penis. Skene’s glands lie lateral and inferior to the urethral meatus and occasionally harbor pathogens such as Neisseria gonorrhoeae. Cysts, abscesses, and neoplasms may arise in these glands.

Distal or caudad to the levator ani muscles, or levator sling is the perineal membrane. This structure is bounded by the ischial tuberosities inferolaterally and by the pubic arch superiorly. Lateral to the perineal membrane are the ischiocavernosus muscles. These structures parallel and are attached to the inferior rami of the symphysis pubis and, like the bulbocavernosus muscles, contain erectile tissue that becomes engorged during sexual arousal. The bulbocavernosus muscles arise in the inferoposterior border of the symphysis pubis and around the distal vagina before inserting into the perineal body. The transverse perinei muscles arise from the inferior rami of the symphysis just anterior to the pubic tuberosities and insert medially into the perineal body, lending muscle fibers to this structure as well.

Musculature of the Pelvic Floor

Internal Genitalia

The levator ani muscles (Fig. 40-2) form the muscular floor of the pelvis. These muscles include, from anterior to posterior, bilaterally, the pubococcygeus, puborectalis, iliococcygeus, and coccygeus muscles. The first two of these muscles contribute fibers to the fibromuscular perineal body. The urogenital hiatus is bounded laterally by the pubococcygeus muscles and anteriorly by the symphysis pubis. It is through this muscular defect that the urethra and vagina pass, and it is the focal point for the study of disorders of pelvic support such as cystocele, rectocele, and uterine prolapse.

Figure 40-3 provides an overhead view of the internal genitalia. The central uterus and cervix are suspended by the lateral fibrous cardinal, or Mackenrodt’s, (uterosacral) ligaments, which insert into the paracervical fascia medially and into the muscular sidewalls of the pelvis laterally. Posteriorly, the uterosacral ligaments provide

Anus

Levator ani muscle Coccygeus muscle

Coccyx

FIG. 40-2. Inferior view of perineal and pelvic muscles.

Bladder

Broad ligament

Uterus

Round ligament External iliac artery and vein

Great saphenous vein Round ligament

Bulbocavernosus muscle Ischiocavernosus muscle Bartholin's gland

Clitoris (glans) Urethral orifice Labium minus Vaginal orifice

Uterosacral ligament

Sigmoid colon

Ovary

Ovarian vessels Ovarian ligament Ureter

Superficial transverse Anus perineal muscle

FIG. 40-1. The external anatomy of the vulva.

Fallopian tube

FIG. 40-3. Internal pelvic anatomy from above.

40/GYNECOLOGY

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Prevesical space Paravesical space

Pubovesical ligament

Vesicovaginal space Vesicouterine ligament

Bladder

Hypogastric plexus

Vesical fascia

Cardinal ligament

Cervix Cervical fascia

Uterosacral ligament

Pararectal space

Retrovaginal space Retrorectal space

Rectum

Obturator nerve Sympathetic ganglion Sacral plexus Left pelvic plexus

Sacrum

FIG. 40-4. The avascular spaces of the female pelvis.

Vesical plexus

support for the vagina and cervix as they course from the sacrum lateral to the rectum and insert into the paracervical fascia. The bilateral fallopian tubes arise from the upper lateral cornua of the uterus and course posterolaterally and anterior to the ovaries. Each widens in the distal third, or ampulla. The ovaries are attached to the uterine cornu by the proper ovarian ligaments. These fibrous bands are analogous to the gubernaculum testis in the male and continue laterally from the uterus as the round ligaments. These structures exit the pelvis through the internal inguinal ring and course through the inguinal canal (canal of Nuck) and external inguinal ring to the subcutaneous tissue of the mons veneris. They insert into the connective tissue of the labia majora. The ovaries are seemingly suspended from the lateral pelvis by their vascular pedicles, the infundibulopelvic ligaments. The peritoneum enfolding the adnexa (tube, round ligament, and ovary) is referred to as the broad ligament, although it is no more ligamentous than the peritoneum overlying the ovarian artery and vein. The peritoneal recesses in the pelvis anterior and posterior to the uterus are referred to as the anterior and posterior cul-de-sacs. The latter is also called the pouch or cul-de-sac of Douglas.

Common iliac artery Internal iliac artery Lateral sacral artery

External iliac artery Superior vesical artery

Rectal plexus Uterovaginal plexus FIG. 40-6. The nerve supply of the female pelvis.

On transverse section (Fig. 40-4), several avascular, and therefore important, surgical planes, can be identified. These include the lateral paravesical and pararectal spaces, and, from anterior to posterior, the retropubic or prevesical space of Retzius and the vesicovaginal, rectovaginal, and retrorectal or presacral spaces. The pelvic brim demarcates the obstetric, or true, from the false pelvis contained within the iliac crests. The muscles of the pelvic sidewall (Fig. 40-5) include the iliacus, the psoas, and the obturator; with the exception of the middle sacral artery, which originates at the aortic bifurcation, the blood supply arises from the internal iliac arteries. The internal iliac, or hypogastric, arteries divide into anterior and posterior branches. The latter supply lumbar and gluteal branches and give rise to the pudendal arteries. From the anterior division of the hypogastric arteries arise the obturator, uterine, superior, and middle vesical arteries. The nerve supply to the pelvis is composed of the sciatic, obturator, and femoral nerves (Fig. 40-6). Sympathetic fibers course along the major arteries and parasympathetics form the superior and inferior pelvic plexus. The ureters enter the pelvis as they cross the distal common iliac arteries laterally and then course inferior to the ovarian arteries and veins until they cross under the uterine arteries just lateral to the cervix. After traveling around to the cervix, the ureters course downward and medially over the anterior surface of the vagina before entering the base of the bladder.

Superoir gluteal artery Inferior gluteal artery Coccygeous muscle Internal pudendal artery Uterine artery Middle rectal artery

DIAGNOSIS Obturator artery Obturator internus muscle

FIG. 40-5. The muscles and vasculature of the pelvis.

Gynecologic History The gynecologic evaluation includes a general history with special emphasis on the function of the reproductive system. The history should include the purpose of the visit; present illness; menstrual and reproductive history, as well as medical, surgical, obstetric, emotional, social, family, and sexual history, including note of any highrisk sexual practices or sexually transmitted disease. Medications,

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allergies, family planning, and a systems review should also be included. The gynecologic history should include the patient’s age, date of her last menstrual period (LMP), the number of pregnancies, the number of deliveries, and the number of abortions. Gravidity, parity, and abortions are frequently indicated as G-P-A. The patient’s menstrual history should include her age at the onset of menses, menstrual interval (time from the beginning of one period until the beginning of the next), number of days of flow, and some description in regard to the amount of flow (light, moderate, or heavy). The examiner should inquire as to when the patient’s last cervical cytology was obtained, and, in patients older than 35 years of age, the date of the patient’s last mammogram should be noted. A description of the patient’s current and recent contraceptive methods should be listed. The age of the patient at the time of her last menstrual period is recorded in postmenopausal patients.

Physical Examination The initial evaluation and the presurgical work-up of a patient should include a general physical examination that includes a description of the patient’s height, weight, nutritional status, blood pressure, head and neck (including thyroid), heart, lungs, and lymph nodes. The gynecologic portion of the examination should document an examination of the breasts, the abdomen, and the pelvis. The pelvic examination is performed on all female patients with a pelvic complaint or on the occasion of their annual gynecologic examination. The patient is examined with her legs comfortably placed in stirrups on an examination table. A good light is essential. Instruments should be warm. Vaginal specula of several sizes must be available. The external genitalia are inspected, noting the distribution and condition of the pubic hair. The glans clitoris, labia, urethral meatus, and the vaginal introitus are evaluated. The condition of the perineum is noted. The anus and perianal area are inspected. The speculum is inserted into the vagina, and the vaginal walls and cervix are studied. A cervical cytology is taken at this time. The speculum is removed, and a bimanual examination of the pelvis is performed (Fig. 40-7). The Bartholin, urethral, and suburethral

FIG. 40-7. Bimanual abdominovaginal palpation of the uterus.

areas are palpated. The vaginal walls are palpated. The cervix is examined, and its consistency, shape, mobility, and tenderness to motion are noted. The uterus and adnexa are evaluated by pressing them between two fingers of the vaginal hand and a hand placed on the lower abdomen. The size, shape, mobility, and tenderness of these organs are noted. After the bimanual examination, a rectovaginal examination should be performed. The middle finger is inserted into the rectum while the index finger is inserted into the vagina. This important maneuver allows the physician to evaluate the posterior surface of the uterus as well as the rectovaginal septum and uterosacral ligaments (Fig. 40-8).

Diagnostic Procedures Cervical Cytology An annual cervical cytology (Papanicolaou [Pap] smear) and pelvic examination should be scheduled for all women who are or who have been sexually active or who have reached 18 years of age. After a woman has had three or more consecutive, satisfactory, annual cytologic examinations with normal findings, the Pap test may be performed less frequently on a low-risk woman at the discretion of her physician (ACOG Committee Opinion Number 186, September 1997).

FIG. 40-8. Bimanual abdominovaginal palpation of the adnexa.

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Table 40-1 The Bethesda Classification for the Classification of Pap Smear Abnormalities Adequacy of the specimen Satisfactory for evaluation Satisfactory for evaluation but limited by . . . (specify) Unsatisfactory . . . (specify) General categorization Within normal limits Benign cellular changes: see descriptive diagnosis Epithelial cell abnormality: see descriptive diagnosis Descriptive diagnosis Benign cellular changes Trichomonas vaginalis Fungus organisms Predominence of coccobacilli Consistent with Actinomyces sp. Consistent with herpes simplex virus Reactive changes Changes associated with inflammation Atrophy with inflammation Radiation Intrauterine contraceptive device

Epithelial cell abnormalities Squamous cell Atypical squamous cells of undetermined significance Low-grade squamous intraepithelial lesion encompassing human papillomavirus High-grade squamous intraepithelial lesion encompassing moderate dysplasia, severe dysplasia, carcinoma in situ Squamous cell carcinoma Glandular cell Endometrial cells, cytologically benign in postmenopause Atypical glandular cells of undetermined significance Endocervical adenocarcinoma Endometrial adenocarcinoma Extrauterine adenocarcinoma Adenocarcinoma, NOS Other malignant neoplasms (specify) Hormonal evaluation (applies to vaginal smears only) Hormonal pattern compatible with age and history Hormonal pattern incompatible with age and history Hormonal evaluation not possible due to . . . (specify)

source: From the International Federation of Gynecology and Obstetrics.

After removal of the uterus and cervix for benign disease, the Pap test is not required as a part of the periodic examination. Except in emergency situations, all women who are having a gynecologic surgical procedure should have had a recent cervical cytologic evaluation. Cervical cytologic specimens are obtained at the time of pelvic examination. The cervix is exposed, and the external cervix is scraped with a suitable spatula. The material is placed on a slide expeditiously fixed with any of the fixatives favored by the cytology laboratory that serves the practice. A sample of endocervical cells is then collected, either with a cotton-tipped applicator or with one of the specialized cytologic brushes. This specimen is then placed on a slide and fixed in the manner of the previous specimen. The practitioner should expect a report from the laboratory in the format of the Bethesda classification (Table 40-1) for cervical cytologic reporting. The Bethesda system for reporting cervical cytologic diagnoses was developed in 1988 and improved in 1991; it replaced the original Papanicolaou reporting system and provides a uniform format for cytopathology reports. All cytologic reports must be studied carefully to determine whether further evaluation or treatment is indicated (Fig. 40-9). Atypical smears or smears with severe inflammation should be repeated generally in 3 months. Persistent (two or more consecutive) atypical smears should be evaluated with colposcopic examination. All smears that indicate dysplasia or neoplasia should be investigated with colposcopy. Colposcopy is a specialized technique that allows evaluation of the cervix under magnification, enabling the practitioner to do directed biopsies of abnormal areas. In many cases, the endocervical canal, which is not directly visible to the colposcopist, is biopsied with a small curette at the time of colposcopic evaluation. Colposcopic examination is important to define the severity and size of

a cervical lesion. The colposcopic examination following abnormal cervical cytology will preempt cone biopsy and allow office treatment of cervical dysplasia in most patients. Colposcopy may find a lesion too large for the ablative procedure that was planned and indicate another approach. When an endocervical lesion is found, the biopsy indicates a lesser lesion than cytologic report, or the biopsy is indicative of microinvasion of the cervix, a cone biopsy is indicated.

Office Tissue Biopsy Biopsy of suspicious lesions of the vulva, vagina, cervix, and uterus should be obtained in the office. Vulvar biopsy is obtained by infiltrating the biopsy site with a small amount of 1% lidocaine using a 27-gauge needle. Adequate biopsies can be obtained using a dermatologic skin punch to the vulvar skin and rotating it slightly. The biopsy then is separated from its base with thumb forceps and a pair of fine scissors. Any bleeding from the biopsy site is controlled with a silver nitrate stick. Biopsy of vaginal lesions is accomplished under local anesthesia. A 25-gauge needle is helpful to reach lesions in the middle or upper vagina. Most lesions of the vaginal wall can be obtained through the use of specialized cervical biopsy forceps or laryngeal biopsy forceps. Biopsy of the cervix does not require anesthesia. Specialized cervical biopsy punches, such as the Kevorkian or Tischler type, are used. The endocervical canal may be sampled with an endocervical curette such as the Kevorkian or Duncan endocervical curette. Biopsy of the endometrial cavity is an office procedure. It is essential to be assured that the patient is not pregnant before performing this procedure. A number of instruments are currently available for this biopsy. The Novak endometrial biopsy curette has been

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Low-Grade Squamous Intraepitheleal Lesion

High-Grade Squamous Intraepitheleal Lesion

Condyloma Mild Dysplasia

Mod/Severe Dysplasia Ca in situ

Persistent Atypia

Atypia Mild/Mod/Severe Dysplasia Ca in situ Condyloma Treat Laser or Cryocautery 5 - FU Other

PAP Smear q 3 mos Yearly after 2 negs

Vaginal Fluid Exam Biopsy Gross Lesions Colposcopy

Invasive Cancer

Microinvasive Carcinoma

Inadequate Colposcopy (or) Positive ECC (or) Incompatible Biopsy/Cytology Laser or Cryocautery Therapeutic Cone Cautery or Hysterectomy

Invasive Cancer

Cone Biopsy

Radical Surgery Radiotherapy

Microinvasive Carcinoma Simple Hysterectomy

Mild/Mod/Severe Dysplasia Ca in situ

replaced largely by sampling devices such as the Pipelle endometrial biopsy instrument or the Vabra suction instrument; these instruments have the advantages of being narrow in caliber, fitting more comfortably into the cervical os, and being entirely disposable.

Vaginal Discharge The patient’s complaint of abnormal vaginal discharge should be investigated. Vaginal secretions that appear abnormal or have a foul odor must be studied. The pH of the vagina, which is normally between 3.8 and 4.4, may be an aid to diagnosis. A vaginal pH of 4.9 or more indicates either a bacterial or protozoal infection. The pH is obtained by dipping a pH tape in the vaginal secretions collected in the vaginal speculum. Vaginal fluid is collected for study by using a cotton-tipped applicator and transferring the sections to a small test tube containing a few drops of saline. The “wet mount” is prepared by placing a small amount of the saline suspension on a microscopic slide with a cover slip and examining it under magnification. The examiner may note motile trichomonads, indicative of Trichomonas vaginalis; characteristic “clue cells,” indicative of bacterial vaginosis; or pus cells, which may be indicative of a variety of vaginal, cervical, and uterine problems, such as gonorrhea, chlamydial, or other bacterial infections. After the initial microscopic examination, a drop of 10% potassium hydroxide is placed on the specimen, and the vaginal material is evaluated again. Potassium hydroxide has the ability to lyse cellular material and enable the practitioner to appreciate the presence of mycelia characteristic of Candida vaginitis.

Cultures Vaginal and cervical cultures are most useful for the detection of sexually transmitted disease. While the diagnosis of gonorrhea might be suspected when gram-negative intracellular diplococci are found on a vaginal smear stained by Gram’s stain, culture should be obtained to prove the infection. Gonorrhea is cultured on a chocolate agar plate and incubated in a reduced oxygen atmosphere. Cultures are most conveniently collected on a Thayer-Martin medium in a bottle containing a carbon dioxide atmosphere.

Special Care

FIG. 40-9. The management of abnormal cytologic findings.

Chlamydial infection is suggested by the finding of a characteristic thick, yellow mucus (mucopus) in the cervical canal. Mucopus should be collected with a calcium alginate–tipped swab and sent to the laboratory in transport media specifically designated for Chlamydia. Some laboratories are now offering urine tests for gonorrhea and Chlamydia using the ligase chain reaction (LCR). This test offers improved sensitivity and specificity for gonorrhea and Chlamydia.

Pregnancy Tests A number of pregnancy tests are available for use in the office. These tests measure increased amounts of the beta subunit of human chorionic gonadotropin (hCG) in urine. These urine tests are very sensitive and specific, measuring hCG as low as 50 mIU/mL. Serum tests are even more accurate and sensitive, and have an advantage in that they can be quantitated to give an hCG level. Serial hCG levels are helpful in circumstances where it is important to determine that hCG levels are increasing or decreasing, such as in the management of threatened abortion, ectopic pregnancy, or trophoblastic disease.

Abnormal Bleeding After the first menstrual period (menarche), cyclic bleeding is considered the norm but is subject to great variation. Menstrual interval varies from 21 to 45 days (time from the beginning of one menstrual period until the beginning of another). Menstrual duration varies from 1 to 7 days. The menstrual flow is a subjective assessment and varies from light to heavy. Some women experience bleeding at midcycle at the time of ovulation. Abnormal genital bleeding falls into six categories.

Bleeding Associated with Pregnancy The availability of extremely sensitive pregnancy tests has made it possible to confirm pregnancy in the early days of gestation. Although bleeding can occur in up to 25% of all normally pregnant women, this symptom must be considered a threatened abortion until the bleeding is otherwise clarified. In the presence of threatened abortion, the pregnancy test is positive, the cervix is closed, and the uterus is generally consistent with the history of gestation. An

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abortion is considered inevitable when the cervix is dilated and fetal tissue appears at the cervical os. Abortion is incomplete after a portion of the products of conception has been expelled; it is considered complete after all the products of conception have been expelled. Inevitable and incomplete abortion is generally treated by dilatation and curettage. Ectopic pregnancy must be considered in any patient with a positive pregnancy test, pelvic pain, and abnormal uterine bleeding. Approximately 20% of patients with ectopic pregnancy have no bleeding, but others might complain of vaginal spotting or, occasionally, of hemorrhage. Gestational trophoblastic disease also causes abnormal bleeding associated with a positive pregnancy test. Most gestational trophoblastic disease is represented by hydatidiform mole. Molar pregnancy is suggested when the uterus is larger than would be expected from the history of gestation, vaginal bleeding, and the passage of grape-like tissue from the vagina. Quantitative gonadotropin levels are almost always greater than expected for the age of gestation. Gestational trophoblastic disease must be differentiated from normal pregnancy. Ultrasound examinations and knowing quantitative gonadotropin levels are helpful in diagnosis.

Dysfunctional Uterine Bleeding This type of bleeding abnormality is characterized by irregular menses with occasional extended intervals of amenorrhea. When bleeding does occur after one of these periods of amenorrhea, it tends to be extremely heavy. The combination of a period of amenorrhea and extremely heavy bleeding occasionally suggests spontaneous abortion. In the majority of instances, the problem is secondary to failure to ovulate. Evaluation of these patients should include a pregnancy test, which should be negative. Endometrial sampling usually reveals a nonsecretory or proliferative endometrium. In the presence of extremely heavy bleeding, dilatation and curettage is occasionally required, but in most instances, the condition can be managed with cyclic estrogen/progesterone treatment.

Trauma The bleeding associated with genital trauma may be diagnosed secondary to a history of rape or genital injury. In the presence of genital bleeding secondary to trauma, the lesion must be evaluated carefully and repaired in the operating room under anesthesia if necessary. In infants and premenarchal patients, the vaginal canal should be examined carefully for foreign bodies.

Bleeding Secondary to Neoplasm Tumors, both benign and malignant, involving the genital tract from the vulva to the ovary, can produce abnormal bleeding. The most important tool in diagnosis is a meticulous pelvic examination that includes visualization of the vulva, vagina, and cervix, and careful bimanual examination of the uterus, tubes, and ovaries. Lesions of the vulva, vagina, and cervix that produce bleeding should be biopsied to exclude malignancy. The most common cause of abnormal bleeding in reproductiveage women are leiomyomas (fibroids). Leiomyomas are almost always benign and are a common cause of heavy noncyclic bleeding (menometrorrhagia). Dilatation and curettage is helpful in diagnosing submucous uterine tumors. Pelvic ultrasound and other forms of pelvic imaging are helpful in the diagnosis of uterine fundal tumors. The bleeding associated with tumors of the fallopian tube and ovary

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is generally scanty and is almost always associated with a palpable pelvic mass.

Bleeding from Infection Bleeding is an uncommon symptom of pelvic inflammation. It is associated most often with inflammatory conditions of the vulva, vagina, and cervix. On rare occasions, patients with endometriosis and acute pelvic inflammatory disease have vaginal bleeding.

Bleeding of a Nongenital Etiology Genital bleeding can be associated with coagulopathy secondary to the use of systemic anticoagulants, clotting disorders, or blood dyscrasias.

Pain Pelvic pain and abdominal pain are common gynecologic complaints. Pain associated with menses is the most common office complaint. Cyclic pain limited to that period just before or with the onset of menses is referred to as dysmenorrhea. Pain occurring without a demonstrable pathologic lesion is referred to as primary dysmenorrhea and is a common feature of ovulatory menstrual cycles. This condition is usually treated satisfactorily with simple analgesics. In some cases producing periodic disability, the use of ovarian suppression with oral contraceptives may be considered. Secondary dysmenorrhea is commonly associated with endometriosis, cervical stenosis, and pelvic inflammation. Acute pelvic pain must be studied carefully. It may have its origin in abnormal pregnancy, benign or malignant neoplasia, or a variety of nongynecologic diseases. Pregnancy disorders include threatened abortion, inevitable abortion, incomplete abortion, and ectopic pregnancy. Neoplasms cause acute pain through degeneration of a myoma or torsion of a myoma or ovarian neoplasm. The spontaneous rupture of an ovarian cyst can produce severe pelvic pain. Pain associated with pelvic malignancy is a late symptom and generally follows other opportunities to diagnose this condition. Common causes of acute pain are salpingitis and endometriosis. Pain secondary to inflammatory conditions is associated with fever and other evidence of infection in most cases. Pelvic infection secondary to C. trachomatis is the exception to this rule. The possibility of a nongynecologic condition as the cause of pain must be always considered. Appendicitis and other acute gastrointestinal problems are also causes of acute pelvic and abdominal pain. Patients with severe abdominal and pelvic pain should be evaluated for urinary problems such as renal and ureteral stones as well as inflammatory conditions of the bladder. In women in the reproductive age group, a differential diagnosis commonly involves appendicitis, ectopic pregnancy, and salpingitis. Readily available, rapidly performed, sensitive, and accurate pregnancy tests have made it possible to quickly exclude the possibility of pregnancy in many situations. Bilateral low abdominal pain increased by movement of the cervix and associated with fever and leukocytosis most often indicates acute pelvic inflammatory disease. Right abdominal pain and tenderness at McBurney’s point, associated with a history of gastrointestinal symptoms, on most occasions, will indicate appendicitis. In many cases it may not be possible to make a definitive diagnosis in the office, and some form of exploratory operation may be required. Direct visualization of the pelvis can be carried out with a laparoscope. Acute appendicitis, ruptured tuboovarian abscess, torsion of a tube or ovary, or an ectopic gestation may indicate celiotomy. The finding of pelvic inflammation in most cases will dictate medical treatment.

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Pelvic Mass The finding of a pelvic tumor is a common event in reproductiveage women. At one time, pelvic examination was the only tool for detection and diagnosis of pelvic tumors, but with increasingly sensitive imaging devices, the surgeon is called to evaluate masses that in the past escaped detection. The clinician must be aware that several physiologic conditions cause enlargement of pelvic organs. Pregnancy should be considered in all cases of uterine enlargement in reproductive-age women. Ovarian enlargement, as a result of ovulation and corpus luteum hematomas, produces masses that are easily palpable and that may persist for several weeks. In addition to a carefully performed pelvic examination, abdominal and vaginal ultrasonography is a useful tool. No imaging method will always distinguish between benign and malignant disease, however. Pelvic ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) all provide clues to the origin of pelvic tumors. Uterine enlargement may suggest pregnancy, uterine myomata, adenomyosis, or malignancy, such as endometrial cancer or sarcoma. Tubal tumors may represent a tubal pregnancy, inflammatory conditions of the tube and hydrosalpinx formation, or a primary fallopian tumor. Ovarian enlargement may suggest endometriosis, ectopic pregnancy, tuboovarian abscess, or benign or malignant tumor of the ovary. The decision to operate is predicated on the patient’s age, clinical presentation, and character and clinical course of the mass. If the differential diagnosis points to a strong possibility of ovarian malignancy, the patient should be explored under conditions that will allow for the treatment of a pelvic cancer.

INFECTIONS Vulvar and Vaginal Infections Vulvar, perineal, and perianal itching and burning are symptoms that may indicate an inflammatory condition. The area is subject to most of the infections that involve skin on any other part of the body. Vulvar infection may be primary on the vulva or can originate in the vagina.

Mycotic Infection The most common cause of vulvar pruritus is candidal vulvovaginitis. The infection is most common in patients who are diabetic, pregnant, or on antibiotics. The majority of cases are caused by C. albicans, although other species may be incriminated. The most prominent symptom is itching; burning of the skin, dysuria, and dyspareunia are also common. Diagnosis is confirmed by examination of the vaginal secretions and recognition of the characteristic pseudomycelia. The condition is treated by the topical application of any one of a number of azole preparations. Intravaginal agents include a number of azole creams generally used over a 3- to 7day period. Systemic treatment is possible through the oral use of fluconazole 150 mg tablet in a single dose.

by recognizing the motile flagellates on microscopic examination. Treatment consists of metronidazole 250 mg given three times daily for 7 days. The vulvar skin is a frequent site for infestation by Phthirus pubis (crab lice) and Sarcoptes scabiei (scabies, itch mites). The primary symptom of both these infestations is severe pruritus. The adult and immature forms are recognized on close inspection of the skin. Treatment consists of a lindane compound, available for medical use as Kwell. The use of this agent is contraindicated in pregnancy.

Bacterial Infections Many bacteria attack the vulvovaginal region; on occasion, bacteria, considered normal inhabitants of the genital tract, cause symptoms. The streptococci and staphylococci are the most common offenders. Bacterial vaginosis is the most common bacterial pathogen. The vaginal discharge found with this condition is not unlike that found with trichomonal vaginitis. The discharge is thin and gray-green in color. The patient complains of a foul, fishy, or “dead mouse” odor. Diagnosis is made by microscopic study of the vaginal secretions to identify characteristic “clue cells.” The condition is treated with metronidazole 500 mg orally every 12 hours for 1 week. Metronidazole and clindamycin topical creams are also effective.

Viral Infections A number of viral infections affect the vulva and vagina, the most common of these being condyloma acuminatum. The causative organism is the human papillomavirus. This infection has increased dramatically in the past 20 years. The lesions are characteristic wartlike growths that begin as single lesions but can grow to huge confluent lesions that distort the normal structures. The lesions enlarge rapidly in pregnancy. Diagnosis is suspected on the basis of appearance and confirmed by biopsy. Treatment depends on the destruction of the lesions with caustic agents, cryocautery, laser ablation, or electrocautery. Some large lesions could require surgical removal. Herpes simplex infection causes painful vesicles followed by ulceration of the vulva, vagina, or cervix. Initial infection is usually widespread, but recurrent infection usually involves a single lesion. Cytologic evaluation of lesions in the vagina is helpful; culture is confirmatory for herpes infection. Once a patient is infected, there is a tendency for the lesions to recur at various intervals for the life of the patient. The attacks may be aborted and the interval between attacks lengthened through the use of acyclovir 400 mg orally three times daily for 7 to 10 days. Active infection in pregnancy carries the risk of newborn infection if the patient delivers vaginally. Cesarean section is recommended in patients in labor with vulvar or vaginal ulceration as a result of herpes simplex infection. Molluscum contagiosum causes groups of small pruritic nodules with an umbilicated center. The lesions are treated by ablation by cautery, curettage, or corrosive medication.

Parasitic Infections Pin worms (Enterobius vermicularis), which are common in young girls, cause vulvitis. Diagnosis is made by finding the adult worms or recognizing the ova on microscopic examination of perianal material collected on adhesive tape. A number of antihelmintic agents are available; mebendazole therapy is commonly used. Trichomonas vaginalis causes primarily a vaginal infection, but the copious vaginal discharge causes secondary vulvitis. The patient complains of heavy, foul-smelling discharge. Diagnosis is made

Pelvic Inflammatory Disease While pelvic inflammatory disease is basically a medical problem, it has profound surgical implications. It is estimated that there are approximately 1.5 million cases of pelvic inflammatory disease in the United States each year. This condition produced approximately 350,000 hospital admissions and could be responsible for more than 100,000 surgical procedures annually. The condition might produce infertility in 10% of the cases that occur; 3% or more of patients

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will have ectopic pregnancy, and chronic pain is a problem in many others. Pelvic inflammatory disease is largely limited to sexually active females. Several factors have been recognized as placing the patient at risk: age younger than 20 years, multiple sexual partners, nulliparity, and previous pelvic inflammatory disease. Pelvic inflammatory disease is classified as acute or chronic. The most common organisms that produce the condition are N. gonorrhoeae and Chlamydia, but numerous other organisms have been incriminated. Diagnosis of pelvic inflammatory disease is based on clinical findings. The classic signs include fever, lower abdominal pain with pelvic tenderness, and purulent vaginal discharge. Some patients, however, will have minimal or absent symptomatology, particularly in the presence of a chlamydial infection. The lack of symptoms does not preclude pelvic inflammatory disease and tubal damage. Those patients who present with an acute illness must be studied thoroughly to rule out the possibility of acute appendicitis, ectopic pregnancy, gastrointestinal obstruction or perforation, and urinary stones. In patients requiring further study, laparoscopy, pelvic ultrasonography, and pelvic CT scanning may be helpful in confirming a diagnosis. When pelvic inflammatory disease is present, laparoscopy will confirm it by finding tubal edema, erythema, and exudate. The presence of a tuboovarian abscess can be confirmed in this manner. Various imaging techniques, such as ultrasound and CT scanning, may also confirm a pelvic abscess.

Treatment Empiric antibiotic treatment of sexually active women who have even minimal symptoms of pelvic inflammatory disease is indicated if no other cause for the symptoms is found. Women with pelvic inflammatory disease can be treated as inpatients or outpatients, depending on the severity of their disease. Patients with evidence of peritonitis, high fever, or suspected tuboovarian abscess should be admitted to the hospital for observation and intravenous antibiotics. Some specialists believe that all women with pelvic inflammatory disease should be admitted to the hospital for more intensive care, which may preserve fertility. The Centers for Disease Control (CDC) recommends one of the following oral regimens: ofloxacin 400 mg orally twice a day for 14 days or levofloxacin 500 mg orally once daily for 14 days with or without metronidazole 500 mg orally twice daily for 14 days. Follow-up of patients treated on an ambulatory basis should be carried out within 48 to 72 hours. If there is no improvement in the patient, she should be admitted for intravenous antibiotics. Recommendations from the CDC for parenteral treatment include cefotetan 2.0 g IV every 12 hours or cefoxitin 2 g IV every 6 hours plus doxycycline 100 mg orally or IV every 12 hours. This regimen is continued for at least 24 hours after the patient shows clinical improvement. Doxycycline 100 mg orally twice daily is given to complete a total of 14 days of therapy. It is now known that the use of broad-spectrum antibiotics, which must include an antibiotic with anaerobic activity, will result in cures of some pelvic abscesses. Some patients may require surgery for persistent abscess or chronic pelvic pain.

Surgical Therapy Surgery becomes necessary under the following conditions: (1) the intraperitoneal rupture of a tuboovarian abscess; (2) the persistence of a pelvic abscess despite antibiotic therapy; and (3) chronic pelvic pain.

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At one time, total abdominal hysterectomy with bilateral salpingo-oophorectomy was considered the procedure of choice when surgery for pelvic inflammatory disease was required. The availability of good antibiotics and a better understanding of the pathophysiology of the disease allow less-radical surgery. In young women whose reproductive goals have not been achieved, especially in the presence of unilateral disease, a unilateral salpingooophorectomy may be more appropriate than total hysterectomy with removal of both ovaries and fallopian tubes. The rupture of a tuboovarian abscess is a true surgical emergency. Physical findings are frequently nonspecific. Rupture is most frequently associated with a sudden severe increase in abdominal pain. A shock-like state commonly accompanies rupture. Leukocyte counts are not necessarily increased, and some patients are afebrile. In the days before surgical intervention for this problem was common, mortality approached 100%. With prompt surgical intervention and intensive medical management, the mortality rate today is less than 5%. The patient with a ruptured abscess must be explored promptly through an adequate incision. Hysterectomy and oophorectomy are commonly indicated. Operation may be technically difficult because of the distortion and edema secondary to the inflammatory process. Before the extirpation of any pelvic organ, adhesions must be lysed and normal structures, such as ureters and the large and small bowel, identified. At the conclusion of the procedure, the abdomen should be liberally irrigated. If the uterus is removed, the vaginal cuff should be left open for drainage. Patients should be treated with high-dose intravenous antibiotics. Because abdominal wound infection is extremely common in these patients, the rectus fascia should be closed securely with a mass closure of the Smead-Jones type. The skin and subcutaneous tissue can be closed but frequently are left open for later delayed closure.

ENDOMETRIOSIS Endometriosis is one of the most common conditions encountered by the pelvic surgeon. It has been estimated that endometriosis will be demonstrated in approximately 20% of all laparotomies in women in the reproductive age group. Although the condition occurs in teenage women, it is found most often in the third and fourth decades of life. Endometriosis persists into the postreproductive years. The exact cause of endometriosis is unknown, but the most common theory is that it is initiated by retrograde menstruation. The theory is supported by the fact that it is extremely common in women who have congenital anomalies of the lower reproductive tract that would favor menstrual reflux. The most common of these anomalies is an imperforate hymen. The most common lesions of endometriosis can be recognized as bluish or black lesions, sometimes raised, sometimes puckered, giving them a “gunpowder burn” appearance. Some lesions are white or yellow, but these are less common. The disease is found most commonly on the ovary, and in many cases will involve both ovaries. Other involved organs can include the uterosacral ligaments, the peritoneal surfaces of the deep pelvis, the fallopian tubes, rectosigmoid, and a number of distant sites, including the skin or even the lungs, diaphragm, and nasopharynx. While many patients are asymptomatic even with widespread endometriosis, others have severe pain, particularly dysmenorrhea, and dyspareunia. Other signs and symptoms depend on the location and depth of endometriotic implants. Infertility and abnormal bleeding are common problems.

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The complaint of pain is common, and in most cases, is characteristic of the disease. Pain is associated most often with the menstrual period, characteristically beginning before the flow starts and ending when bleeding is complete. Deep pelvic dyspareunia is commonly associated with this disease, particularly in those individuals with implants involving the uterosacral ligaments or the rectovaginal septum. The finding of a pelvic mass and tender nodularity of the uterosacral ligament strongly suggests endometriosis. The mass usually represents an ovarian endometrioma, often referred to as a “chocolate cyst” because of its dark-brown fluid contents. Endometriomas are found in approximately one-third of women with endometriosis and are often bilateral. Endometriotic involvement of the skin, mucous membranes, or peritoneum is characteristically a bluish discoloration, which will bleed or cause discomfort at the time of menstruation. Although endometriosis may be suspected on the basis of clinical findings and the patient’s history, the definitive diagnosis is made visually, usually with the aid of a laparoscope. Biopsy may be helpful in atypical cases. Medical management of this condition should not be started without a confirmed diagnosis. Laparoscopy offers the best diagnostic opportunity for this disease.

Treatment Choices of treatment include expectant management only, medical management, and surgery. Patients with minimal endometriosis who are asymptomatic can be cared for through simple observation and management with cyclic oral contraceptives and simple analgesia. The medical management of this condition involves the use of a number of agents in several pharmacologic classes. Progestins have been used for the management of endometriosis for many years. Medroxyprogesterone acetate is given orally. The agent is used in doses of 10 mg two to three times daily and frequently provides symptomatic relief. Pseudomenopause is currently the most common medical treatment for endometriosis. The most common medications used today for this purpose are the gonadotropin-releasing hormone agonists (GnRHa). These agents produce a suppression of ovarian function by suppression of both follicle-stimulating hormone and luteinizing hormone as a result of continuous stimulation of pituitary GnRH receptors. These agents have low toxicity, and while they reliably produce the hypoestrogenic effects of hot flashes and vaginal atrophy, these symptoms are generally well tolerated. They can be given by depot injection or daily nasal spray. Because bone loss is also a result of hypoestrogenism, it is recommended that the treatment not be continued for more than 6 months. In the past, medications were used to create a pseudomenopause. These agents suppress pituitary gonadotropins by negative hypothalamic feedback. The resulting ovarian suppression produces endometrial atrophy and regression of ectopic endometrium. Along with vasomotor symptoms and vaginal atrophy, this medication has many other symptoms, including weight gain, muscle cramps, and signs of androgen excess, including oily skin, acne, and hirsutism. For this reason, it has been replaced largely by either GnRHa or progestin therapy for the medical treatment of endometriosis. All these medical therapies have been well documented to result in temporary relief in patients with symptomatic endometriosis. In some patients, the effects can be relatively long lasting, but complete, permanent regression of endometriosis is rare with medical therapy. Although these treatments are used widely to enhance fertility, there

is little evidence that medical therapy actually increases pregnancy rates compared with expectant therapy. Conservative surgical therapy for endometriosis has become much more common with the advancement of laparoscopic surgery. At the time of initial diagnosis, superficial endometrial implants can be ablated with electrocautery or laser, and ovarian endometriomas can be removed. This approach appears to result in short-term enhancement of fertility and may give substantial temporary pain relief. In some cases of severe pain, deep retroperitoneal endometriosis implants can be removed either by laparoscopy or laparotomy with good results. However, as with medical therapy, conservative surgical treatment for endometriosis is palliative rather than curative in most patients. The approach to ovarian endometriomas deserves special consideration. These “chocolate cysts” cannot be treated effectively medically. In general, even large endometriomas can be drained and the cyst lining removed laparoscopically. Although it was recommended in the past to close the ovary with several layers of absorbable sutures, it appears that this approach tends to increase postoperative adhesion formation. For this reason, it is recommended that after hemostasis is achieved, the ovary should be left open to close spontaneously. Other methods to minimize adhesion formation include atraumatic handling of the tissues and the use of a cellulose-adhesion barrier (Interceed) over the surgical site. Several series document pregnancy of approximately 50% rates following conservative operation. Extirpative surgery is the only permanent treatment for symptomatic endometriosis. Patients with symptomatic endometriosis whose reproductive goals have been achieved may have no interest in preserving their reproductive potential. In these circumstances, extirpation of the endometriosis, along with the patient’s fallopian tubes, ovaries, and uterus, may be the best choice. If extirpative surgery has been chosen, removal of all ovarian tissue has been advocated in the past to prevent the stimulation of residual endometriosis or the development of the residual ovary syndrome. In younger patients, a normal ovary may be spared in some cases. If total hysterectomy with bilateral salpingo-oophorectomy is required, replacement hormone therapy is indicated and recurrence is uncommon. To minimize the risk of recurrent endometriosis, it is recommended that replacement hormones include daily estrogen combined with a progestin such as medroxyprogesterone acetate, 2.5 mg given orally.

ECTOPIC PREGNANCY Ectopic pregnancy affects a large number of women of reproductive age in this country. The incidence of this condition has increased dramatically over the last two decades. Because of improvements in diagnostic and therapeutic approaches, however, maternal mortality has declined over the same period of time. Women in the reproductive age group have an increased risk of ectopic pregnancy as they age. Women in the last 10 years of their reproductive life have more than three times the risk of women in the first 10 years of reproductive life. Black and Hispanic women have a higher risk than white women. A history of salpingitis is common in women with ectopic pregnancy. Sterilization protects against ectopic pregnancy, but when sterilization methods fail, the risk of tubal implantation is increased. The most common complaint of patients with ectopic pregnancy is pain, frequently associated with irregular vaginal bleeding. Approximately 80% of affected women will recall a missed menstrual

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period. Physical findings include abdominal tenderness on cervical motion and adnexal tenderness on bimanual pelvic examination. An adnexal mass may be palpated in approximately 50% of patients. As a result of the intraperitoneal bleeding, some patients present in shock. The most helpful laboratory examination is measurement of the beta subunit of hCG (beta-hCG). Modern-day testing, with a sensitivity of 50 mIU/mL or less, enables the surgeon to confirm the pregnant state in almost all patients at risk for ectopic pregnancy. Once the physician is assured that the patient is pregnant, it must be determined that the pregnancy is in the uterus. Pelvic ultrasonography, particularly when performed with a vaginal transducer, is proving important in differentiating uterine gestations from ectopic gestations. If the patient’s condition is not emergent, the serum level of betahCG at 24- to 48-hour intervals is followed. In a normally implanted pregnancy, hCG levels will double every 2 days in early pregnancy, enabling the surgeon to separate normally implanted pregnancies from those with impending abortion or those located in an ectopic site. Ultrasonic evaluation of the pelvis is increasingly important. The vaginal probe enables the clinician to determine whether the developing pregnancy is in the uterus or in the tube at a time when the hCG levels are barely more than 1000 mIU/mL. Significant intraperitoneal hemorrhage also can be visualized by vaginal ultrasound. However, culdocentesis remains an expedient means to determine the presence of hemoperitoneum in an emergency situation. In those patients who do not desire to continue the pregnancy, curettage of the uterus with examination of the tissue can be diagnostic. In the event that fetal tissue is not found, a diagnostic laparoscopy is usually required in the symptomatic patient for definitive diagnosis. In the presence of hemodynamic instability or significant intraperitoneal bleeding that precludes adequate visualization of the pelvis, immediate laparotomy is indicated.

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serially coagulated with bipolar cautery and transected with scissors. When the uterotubal junction is reached, the tube is desiccated with bipolar cautery, and the entire tube and pregnancy are removed with the aid of a specimen bag and a large port.

Abdominal Operation In those cases in which the surgeon has elected to perform a laparotomy, the same treatment options exist that were available laparoscopically. In a patient who desires future pregnancy, every attempt should be made to preserve a functional fallopian tube. If linear salpingostomy cannot be performed, consideration should be given to midsegment resection. Midsegment resection invariably shortens the tube but preserves the fimbria, which allows later reanastomosis. Salpingectomy should be reserved for those patients who have completed their reproductive goals, for those patients in whom salpingostomy has failed, and for those patients whose tube has been so completely destroyed by the ectopic gestation that it cannot be salvaged.

Medical Therapy A relatively new approach to ectopic pregnancy is the use of methotrexate. Conservative criteria for treatment of ectopic pregnancy with methotrexate include serum beta-hCG levels less than 3500 IU/L and vaginal ultrasound that reveals the tubal pregnancy to be less than 3.5 cm in diameter with no visible fetal cardiac motion and no sign of hemoperitoneum. In this situation, studies show that administration of intramuscular methotrexate will result in complete resolution of the ectopic pregnancy in 96% of the cases. Subsequent tubal patency on the affected side can be documented in approximately 85% of the patients so treated. The risk of rupture and intraperitoneal hemorrhage must be made clear to the patient. In these cases, surgical management can be lifesaving. To what degree methotrexate treatment of ectopic pregnancy will replace definitive surgery has yet to be established.

Treatment Once a diagnosis of ectopic pregnancy has been established, several choices are available for treatment.

Laparoscopic Procedures The laparoscope has been an important diagnostic tool for the last several decades, but only recently has it become the standard approach for treatment. Linear salpingostomy is the treatment of choice for ectopic pregnancies less than 4 cm in diameter that occur in the distal third (ampullary) segment of the tube. To aid in hemostasis, the mesentery below the involved tubal segment is infiltrated with a dilute vasopressin solution. The tube may then be opened in its long axis along the antimesenteric side with either a laser or a unipolar cutting cautery. The conceptus is then aspirated, and any bleeding is electrocoagulated with bipolar cautery. Closing the tube is not necessary because the tube closes spontaneously in almost every case. If hemostasis cannot be achieved, coagulation of a portion of the mesosalpinx just below the segment may be required. Partial or total salpingectomy is indicated when the pregnancy is located in the isthmic portion of the tube. Bipolar electrocoagulation is used to desiccate a short segment of fallopian tube on either side of the pregnancy, and the pregnancy and tubal segment are removed together. Larger ectopic pregnancies are managed by total salpingectomy because adequate hemostasis is difficult to achieve without extensive tubal damage. For this procedure, the mesosalpinx is

PELVIC FLOOR DYSFUNCTION Pelvic Organ Prolapse Female pelvic floor dysfunction is common. It includes many clinical conditions, the most prevalent of which are pelvic organ prolapse and urinary incontinence. The muscles and connective tissues that comprise the pelvic floor and support the pelvic organs can be injured directly or indirectly by neuropathy. Different manifestations of pelvic floor dysfunction often coexist in the same patient owing to shared risk factors. Race, collagen metabolism, vaginal delivery, chronic constipation, chronic lung disease, and smoking are among the factors thought to be associated with the development of pelvic floor dysfunction. The percentage of women who have undergone at least one surgical operation for prolapse or incontinence by age 80 years is 11.1%, and of those nearly 30% undergo reoperation for recurrence of symptoms. The word “prolapse” is a Latin derivative, meaning “to slip or fall.” Pelvic organ prolapse is the descent of the pelvic organs into or through the vagina because of deficient support of the vaginal walls. The various types of pelvic support defects seldom occur as isolated problems. Consequently, labels such as “cystocele,” “rectocele,” and “enterocele” can be misleading to both patients and practitioners because of their implication that a specific organ has lost support rather than the vaginal vault itself. The standardization report of the International Continence Society in 1996 named

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D C

3 cm

Ba Aa Bp Ap

gh

tvl

pb

FIG. 40-10. Six sites (points Aa, Ba, C, D, Bp, and Ap), genital hiatus (gh), perineal body (pb), and total vaginal length (tvl) used for pelvic organ support quantitation.

“anterior vagina,” “posterior vagina,” and “vaginal apex” as reference points in the description of pelvic organ prolapse. This terminology, known as the Pelvic Organ Prolapse Quantification (POP-Q) system, quantifies prolapse according to the positions of those reference points relative to the hymen. The POP-Q has replaced the arbitrary grading systems that have been used in the past, improving the quality of description of the examination findings and facilitating communication among practitioners. It is easily learned and reliable. Measurements are taken at maximum Valsalva, preferably in the sitting or standing position. Figure 40-10 represents the locations of the reference points on the vaginal walls, as well as two external measurements and the vaginal depth. Figure 40-11A is a diagrammatic representation of normal and complete prolapse using the standardized system. Figure 40-11B depicts how predominantly anterior or posterior vaginal prolapse is quantified. Figure 40-11C shows the staging system. Most reconstructive operations are performed for Stage II or greater prolapse. A majority of vaginally parous women have stage II prolapse; most of these are asymptomatic and do not require surgery. Patients with symptomatic pelvic organ prolapse report pelvic pressure and heaviness or a bulge protruding through the vagina. These symptoms are most often worst at the end of the day, or after prolonged physical activity or standing. Patients may report difficulty with bowel or bladder emptying, which requires them to push the prolapsed tissue back in manually. Obstructed voiding may occur, predisposing to urinary tract infection, urinary frequency and urgency, or, in rare cases, hydroureter and hydronephrosis. Because of shared risk factors, many patients with prolapse also have urinary incontinence. However, the relationship between urinary incontinence and prolapse is complex. Advanced prolapse may be associated with paradoxical continence, in which obstruction of the urethra by the prolapse masks symptoms of stress incontinence which would otherwise occur because of a defective urethral closure mechanism. Many patients with varying degrees of prolapse report generalized pelvic discomfort or backache. However, these symptoms are common and multifactorial and may not be a direct result of prolapse. Reconstructive surgery is indicated for cases of stage II or greater prolapse from which the patient is symptomatic, whether from

discomfort, irritation, or disturbance of bowel and bladder function. Not all patients with prolapse require surgery. It is important to carefully define which of the patient’s symptoms can be reasonably expected to improve with an operation. Certain patients may prefer to avoid surgery or be inappropriate surgical candidates; for those, a pessary trial is often recommended. A pessary trial may also help, when a patient’s symptoms are disproportionate to her physical findings, to identify which symptoms are attributable to prolapse. Some patients with mild prolapse may achieve relief with a physical therapy program. Patients with chronic constipation often experience significant improvement after instituting a high-fiber diet. The reconstructive pelvic surgeon must recognize pelvic organ prolapse as a quality-of-life issue. This means that surgical goals and outcomes are measured not only by restoration of anatomy, but by relief of specific symptoms with which the patient presents.

Urinary Incontinence Urinary incontinence is defined as involuntary leakage of urine. It may be subdivided into several conditions. Stress urinary incontinence is leakage of urine on exertion or effort, or with sneezing or coughing, which can be objectively demonstrated. It results from a dynamic urethral closure mechanism that is insufficient to overcome increases in abdominal pressure. Urge incontinence, by contrast, is characterized by urine leakage that is accompanied or immediately preceded by urgency. Urge incontinence is thought to result from inappropriate activation of the micturition reflex (“overactive bladder”). Stress incontinence, but not urge incontinence, is amenable to surgical therapy. However, the symptom of stress incontinence is not specific, and may occur in patients with incontinence caused by other bladder disorders. A baseline physical examination for a patient complaining of urinary incontinence includes a standing stress (cough) test, pelvic examination—including prolapse staging and evaluation for pelvic mass—urinalysis, and postvoid residual determination. Urethral mobility may be evaluated using the cotton swab (Q-Tip) test. A sterile cotton swab lubricated with local anesthetic gel is inserted to the urethrovesical junction. The angle of the swab relative to the floor is measured at rest and at maximum Valsalva maneuver. Urethral hypermobility is defined as an excursion of 30 degrees or greater. Urethral hypermobility often serves as a focus for repair in continence operations. It is important to note, however, that urethral hypermobility is not specific for, nor causative of, urinary incontinence. A patient presenting with symptoms and objective confirmation of stress urinary incontinence, with a normal pelvic examination, prolapse of stage II or less, a normal urinalysis, normal postvoid residual, and urethral hypermobility may be a candidate for surgical therapy. However, many patients have factors that complicate their condition. These include a history of previous incontinence or prolapse surgery; prolapse greater than stage II; elevated postvoid residual or abnormal voiding function; urinary urgency, frequency, or symptoms of urge incontinence; hematuria; neurologic disease; and previous pelvic radiation or radical pelvic surgery. Those patients should undergo complex urodynamic studies and evaluation by a pelvic floor specialist prior to consideration of an incontinence operation. Stress urinary incontinence may be treated conservatively or surgically. Conservative management before surgery for most patients is recommended by the National Institute of Health’s Agency for Health Care Policy and Research. Two of the most commonly used conservative treatments are pelvic floor physical therapy and a continence ring or dish. Patients are frequently instructed to perform

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Aa Ba

xx

Aa

x

x C

C Bp Ba

xx x

x

x

Bp

x

Ap

Ap

+3 Aa +6 Ba -2 C

-3

4.5 gh 1.5pb

6 tvl

4.5 gh

--

+2

-3

Ap

-2

Bp

A

1 pb

Ap

+5

Bp

8 tvl --

B

Ba Aa X X

Aa X

Ba X CX X Bp

X X Ap Bp

X Ap

4.5 gh 1.5pb +3

Ap

+8

Bp

-3 Aa -3 Ba -8 C

8 tvl

2 gh

--

-3

Grid A COMPLETE EVERSION OF VAGINA C

pelvic muscle exercises, or “Kegels,” to treat pelvic floor dysfunction. However, brief verbal instruction in exercise technique may be inadequate. Physical therapy for incontinence emphasizes strengthening of the pelvic floor muscles, often in concert with bladder retraining, urge deferment techniques, and education in lower urinary tract function. A continence dish is a flexible latex or silicone device

XD

X C

+3 Aa +8 Ba +8C

FIG. 40-11. A . Diagram of normal and complete prolapse using the standardized system. B . Quantification of anterior or posterior vaginal prolapse. C . Staging system for quantifying anterior and posterior vaginal prolapse.

-3 Ba -6 C

Aa

Ap

3 pb 10tvl -3

Bp

-10

D

Grid B NORMAL SUPPORT

worn intravaginally in order to mechanically obstruct the urethra. Estrogen supplementation and alpha-adrenergic medications have been advocated for the treatment of stress incontinence, but their efficacy remains unproven. Continence is a dynamic, complex function which surgery attempts to restore by compensatory means. The goal of a continence

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operation is to improve the ability of the urethra to close with increases in abdominal pressure, yet avoid impairing voiding function. Surgical treatments for urinary incontinence have been performed since the beginning of the twentieth century, pioneered by Howard Kelly and other gynecologic surgeons. Hundreds of different of operations have been developed, a fact that testifies to the difficulty of consistently achieving satisfactory and long-lasting outcomes.

SURGERY FOR PELVIC ORGAN PROLAPSE Many factors are important in determining which reconstructive operation is optimal for a given patient. Vaginal, abdominal, and laparoscopic approaches have been used. The most popular operation for uterovaginal prolapse has historically been vaginal hysterectomy with colporrhaphy. It may be combined with procedures designed to support the vaginal apex, such as uterosacral or sacrospinous ligament suspension. The abdominal approach to prolapse includes suspension of the vaginal apex to the sacrum using synthetic mesh. Many variations of each operative technique have been described. Surgical decisions are often based on case series and expert opinions which may not have universal applicability. There are few controlled studies in the literature reporting on standardized techniques that include meaningful outcome comparisons and long-term follow-up. Those that have been published suggest that failure rates for vaginal reconstruction may be twice as high with the vaginal route as with the abdominal route. The preponderance of the vaginal route is therefore being challenged. In patients with an intact uterus, hysterectomy accompanies prolapse repair. Hysterectomy itself is not treatment for uterovaginal prolapse, which is caused by defective anatomic support structures. However, most prolapse repairs cannot be performed effectively with the uterus in place. An exception is the LeFort partial colpocleisis, which obviates the need for hysterectomy. Prolapse surgery is best reserved for the patient who has completed childbearing. Removal of the ovaries is performed according to age-appropriate indications.

Vaginal Procedures Colporrhaphy The oldest type of vaginal reconstructive operation is colporrhaphy. Widely used in the mid-nineteenth century, these procedures involved destroying or removing parts of the vaginal epithelium and reapproximating the edges to reduce vaginal caliber. Modern-day colporrhaphy, also known as “anterior repair” or “posterior repair,” involves excision of vaginal epithelium and as such differs little from the original techniques. Anterior colporrhaphy begins with incision of the anterior vaginal epithelium in a midline sagittal direction. The epithelium is sharply dissected away from the underlying vaginal muscularis. Although many surgical descriptions refer to plication of the “endopelvic” or “pubocervical” fascia, such structures have not been shown to exist as histologically distinct layers. The vaginal muscularis is plicated with interrupted delayed absorbable stitches, following which the epithelium is trimmed and reapproximated. The vaginal canal is shortened and narrowed proportionate to the amount of removed epithelium. Posterior colporrhaphy is performed in a similar manner, often including the distal pubococcygeus muscles in the plication. In addition to the vaginal shortening and neuropathy, which may be induced by these dissections, levator plication is associated with a significant risk of postoperative dyspareunia. These factors influence the selection of appropriate patients for colporrhaphy procedures.

Sacrospinous Fixation Sacrospinous ligament suspension of the vaginal vault was introduced in the United States in 1971. The sacrospinous ligament is used as a unilateral fixation point for the vaginal apex. The procedure begins with entry into the rectovaginal space, usually by incising the posterior vaginal wall at its attachment to the perineal body. The space is developed to the level of the vaginal apex. The rectal pillar is penetrated to gain access to the pararectal space. The sacrospinous ligament is found embedded in, and continuous with, the coccygeus muscle which extends from the ischial spine to the lateral surface of the sacrum. A long-ligature carrier is used to place a nonabsorbable monofilament suture two fingerbreadths medial to the ischial spine, through the substance of the ligament-muscle complex rather than around it, in order to minimize the risk of injury or entrapment of the pudendal neurovascular bundle. Other structures at risk of injury in this area include the inferior gluteal neurovascular bundle, lumbosacral plexus, and sciatic nerve. Two stitches are placed, the free ends of which are sewn to the undersurface of the vaginal cuff. After reapproximation of the proximal vaginal epithelium, the sacrospinous stitches are tied to firmly approximate the vagina to the ligament without suture bridging. The remainder of the epithelial incision is then closed.

Uterosacral Ligament Suspension Like sacrospinous fixation, suspension of the vaginal apex to the uterosacral ligaments may be performed immediately following vaginal hysterectomy or applied to posthysterectomy vaginal vault prolapse. This approach is based on the original description of posterior culdoplasty by McCall in 1957. The procedure is based on the concept that the natural superior, or level I, support structures for the vagina are the uterosacral ligaments. The repair is designed to restore those attachments and to bring the ligaments together in the midline to occlude the posterior cul-de-sac. When using the uterosacral ligaments for repair of prolapse, it is important to recall that these structures are not “ligaments” in the true sense of the word, but rather condensations of smooth muscle, collagen, and elastin. The integrity and strength of these structures may vary greatly from patient to patient. The uterosacral ligaments are exposed with an intraperitoneal approach. Studies suggest the strongest part of the ligament is the proximal third. The repair uses the middle third of the ligament, which allows firm tissue-to-tissue approximation to the vagina and does not divert the ureter medially. Delayed absorbable or permanent suture is used, keeping in mind that permanent suture material must be buried beneath the vaginal epithelium, within the muscularis and away from the lumen. Several support stitches are placed, such that the lateral-most portion of the vaginal cuff is attached to the distal-most part of the ligament and the medial cuff to the proximal ligament. Many variations on the technique of uterosacral vault suspension have been described. Ancillary repair of anterior or posterior wall prolapse may be performed concurrently. Intraoperative evaluation of the lower urinary tract is important to confirm the absence of ureteral compromise.

Colpocleisis Colpocleisis is the term applied to a class of vaginal prolapse operations that involve removal of part or all of the vaginal epithelium. These procedures do not correct any anatomic defect, but rather obliterate the vaginal vault, leaving the external genitalia unchanged. Colpocleisis is reserved for patients who are elderly, who do not wish to retain coital ability, and for whom there is good reason not to perform a more extensive reconstructive operation. The

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main benefits of colpocleisis operations are their simplicity, speed, and high efficacy. The LeFort colpocleisis technique, done for complete uterovaginal prolapse, requires preoperative screening of the cervix and endometrium for malignancy. The procedure involves denudation of a rectangular portion of vaginal epithelium on both the anterior and posterior walls using sharp dissection, followed by suture reapproximation of the exposed submucosal surfaces. The uterus is left in situ. Lateral drainage canals remain for drainage of uterine secretions. By contrast, total colpocleisis involves hysterectomy (if applicable), followed by excision of the entire anterior and posterior epithelium. Successive purse-string sutures through the vaginal muscularis are used to reduce the prolapsed organs to above the level of the levator plate. In both partial and total colpocleisis, the pubococcygeus muscles may be plicated together in the rectovaginal space, together with a wide perineorrhaphy. Because the bladder neck is displaced posteriorly by the repair, placing the patient at risk for postoperative stress incontinence, a concomitant procedure to stabilize the urethrovesical junction is recommended. This may involve plication of the anterior vaginal muscularis (Kelly plication), pubourethral ligament plication, or a sling procedure, depending on preoperative urodynamic findings.

Abdominal Procedures Sacral Colpopexy Pelvic reconstructive surgery by the abdominal approach has as its main advantage the use of graft material for support of the vaginal apex. The natural apical support structure, the cardinal–uterosacral ligament complex, is often damaged and attenuated. The use of graft material to compensate for defective vaginal support structures is well described. Suspension of the vaginal vault to the anterior surface of the sacrum using graft material was first reported in 1962. As noted earlier, apical support defects rarely exist in isolation. Therefore, the sacral colpopexy may be modified to include the anterior and posterior vaginal walls, as well as the perineal body, in the suspension. Abdominal sacral colpoperineopexy begins with the attachment of graft material to the perineal body. The rectovaginal space is opened, as with a posterior colporrhaphy, carrying the dissection laterally to the crura of the pubococcygeus muscles and opening the posterior cul-de-sac peritoneum. An allograft or xenograft trimmed to the appropriate dimensions is anchored to the levator ani muscles bilaterally and the perineal body distally, using delayed absorbable or permanent monofilament suture in interrupted fashion. The vaginal epithelium is then reapproximated and a perineorrhaphy constructed. Synthetic mesh is not used in the distal rectovaginal space because of its propensity for erosion into the distal vagina, particularly underneath the suture line. Laparotomy is then performed and the graft is retrieved. A rigid stent is placed into the vagina to facilitate its dissection from the overlying bladder and to allow the graft material to be spread evenly over its surface. A strip of synthetic mesh is fixed to the remainder of the posterior vaginal wall directly and another to the anterior wall. The peritoneum overlying the presacral area is opened, extending to the posterior cul-de-sac. Retracting the sigmoid colon medially, the anterior surface of the sacrum is skeletonized. Two to four permanent sutures are placed through the anterior longitudinal ligament in the midline, starting at the S2 level and proceeding distally. The sutures are passed through both leaves of the graft at the appropriate location which supports the vaginal vault under no tension. The peritoneum is then closed with an absorbable running suture. Retroperitoneal

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placement is important to minimize the risk of graft adherence to abdominal viscera. The most dangerous potential complication of sacral colpopexy is life-threatening sacral hemorrhage. Sacral osteomyelitis has also been reported.

SURGERY FOR STRESS URINARY INCONTINENCE There is a multitude of studies addressing the efficacy of different surgical procedures for urinary incontinence. The interpretation of this literature is often difficult, owing to the lack of standardized definitions. Diagnostic entities such as “stress incontinence,” “intrinsic sphincter deficiency,” and “voiding dysfunction” have no set criteria. The same surgical procedures are often performed with a variety of modifications unique to each operator. In addition, outcome criteria, particularly the definition of “cure,” are not uniformly defined. As a result, adequate comparison of results among patients with a given procedure, or among procedures, is difficult. The choice of an incontinence operation for a given patient may depend in part on her symptoms. Intrinsic sphincter deficiency (ISD) is a term applied to a subset of stress-incontinent patients who have particularly severe symptoms, including urine leakage with minimal exertion. This condition is often recognized clinically as the “low pressure” or “drainpipe” urethra. The urethral sphincter mechanism in these patients is severely damaged, limiting coaptation of the urethra. There are no set specific or objective criteria that define ISD, although urodynamic criteria are often used to support it. In cases of uncomplicated stress incontinence accompanied by urethral hypermobility, retropubic colposuspension is most commonly used. In the presence of intrinsic sphincter deficiency, success rates with colposuspension may be less than 50%. Therefore, ISD with urethral hypermobility is best treated with suburethral sling procedures. ISD may also exist without urethral hypermobility, often when the urethra is fixed and scarred from multiple previous operations or from radiation therapy. In such cases, suburethral slings, periurethral bulk injections, or, rarely, artificial sphincters are used. The need to perform concurrent operations with incontinence surgery, most often reconstructive operations for prolapse, may also direct the type of procedure performed and whether it is done by the abdominal or vaginal route. Standard surgical procedures used to correct stress incontinence share a common feature: partial urethral obstruction that achieves urethral closure under stress. Despite older literature to the contrary, this objective does not require that the bladder neck be “elevated to a high retropubic location.” Many types of operations, in fact, achieve their surgical objectives without changing the anatomic position of the urethra. Incontinence operations fall into one of three categories: needle suspension, retropubic urethropexy, and suburethral sling. Anterior vaginal wall plication, or anterior colporrhaphy, is no longer advocated for the surgical treatment of stress incontinence.

Needle Suspension The transvaginal needle suspension was first described in 1959 by Pereyra. Variations on this technique include the Stamey, Gittes, and Raz procedures. After an anterior colpotomy is made, the vaginal epithelium is dissected and mobilized to the level of the descending pubic rami. The space of Retzius is entered bilaterally using a blunt clamp or closed heavy Mayo scissors to penetrate the perineal membrane along the inferior aspect of the descending pubic ramus. Through a small transverse suprapubic incision a long, angled needle is passed through the rectus fascia through the space of Retzius to bring up the ends of a suture that has been secured to the

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periurethral vaginal muscularis. Variations exist with regard to the way in which suture is attached to the periurethral tissue as well as the method of abdominal wall fixation. Long-term studies of needle procedures have shown evidence of steadily increasing failure rates, likely a result of suture pullout from the periurethral vaginal tissue.

Retropubic Colposuspension The first retropubic colposuspension was described in 1949 and modified in 1961. From an abdominal approach, the space of Retzius is approached extraperitoneally, allowing the bladder to be mobilized from the surrounding adipose tissue and lateral pelvis. Overlying fat and blood vessels in the area of the vesical neck are cleared away.

Marshall-Marchetti-Krantz (MMK) Procedure Permanent suture is placed lateral to the urethra bilaterally and tied to the periosteum of the pubic ramus or perichondrium of the symphysis pubis. The surgical objective is to appose the urethra to (or within 1 to 2 cm of) the posterior surface of the symphysis pubis. Osteitis pubis (a rare, but serious, potential complication that can result from trauma and devascularization of the symphysis), as well as suture pullout from the symphysis, prompted the search for improved techniques.

Burch Procedure Of the many descriptions, the most quoted is that of Tanagho in 1976. Two pairs of large-caliber delayed-absorbable suture are placed through the periurethral vaginal wall, one pair at the midurethra and one at the urethrovesical junction. Each stitch is then anchored to the ipsilateral Cooper’s (iliopectineal) ligament. With the operator’s nondominant hand placed vaginally, the distal and then proximal sutures are tied to give preferential support to the urethrovesical junction relative to the anterior vaginal wall without overcorrection. Specifically, two fingerbreadths of space between the urethra and pubic bone are recommended. Long-term outcome studies up to 10 years have shown cure rates of 80 to 85% for the Burch procedure. With all retropubic colposuspensions, the anterior displacement of the vagina is associated with a 7 to 20% risk of postoperative enterocele. Therefore, concurrent obliteration of the posterior cul-de-sac is advised.

Suburethral Sling Suburethral sling procedures for stress incontinence have been in use since the beginning of the twentieth century. The early techniques involved the use of gracilis muscle, pyramidalis muscle, and rectus fascia flaps. A variety of organic and synthetic graft materials have been used to construct suburethral slings. Synthetic materials fell out of favor after a high incidence of postoperative urinary retention and urethral damage were found to be associated with their use. Currently, the most commonly used sling materials include autografts (rectus fascia) and processed cadaveric allografts (fascia lata). The procedure is performed by a combined abdominovaginal approach, using a small transverse suprapubic skin incision. The anterior vaginal epithelium is incised in the midline from the midurethra to just proximal to the urethrovesical junction, as identified by the bulb of an indwelling urethral catheter. The epithelium is dissected from the underlying muscularis using sharp dissection bilaterally. The space of Retzius is entered using a blunt clamp or closed heavy Mayo scissors to penetrate the perineal membrane along the inferior aspect of the descending pubic ramus. Maintenance of the proper angle of penetration is important to minimize

the risk of injury to the obturator neurovascular bundle or ilioinguinal nerve laterally, and urethra or bladder medially. A Bozeman clamp or long-angled ligature carrier is used to perforate the rectus fascia two fingerbreadths superior to the pubic bone just medial to the pubic tubercle, and the instrument is guided along the back of the pubic bone through the space of Retzius and into the vaginal incision to retrieve one arm of the sling. After bringing up the other side of the sling, and confirming the absence of urinary tract injury, the sling arms are fixed in place such that a sterile cotton swab placed to the urethrovesical junction is 5 to 10 degrees from the horizontal. Most often the sling arms are sutured to the rectus fascia, although procedures using pubic bone anchors also have been described. The base of the sling is positioned at the urethrovesical junction. Cure rates for the many different types of sling procedures described in the literature range from 75 to 95%. Slings are associated with higher complication rates than most other incontinence procedures, most frequently involving voiding dysfunction, urinary retention, new-onset urge incontinence, and foreign-body erosion.

Tensionless Sling The tension-free vaginal tape (TVT) procedure was introduced in 1996. It is a modified sling that uses a strip of polypropylene mesh. Unlike traditional sling procedures, the mesh is positioned at the midurethra, not the urethrovesical junction, and is not sutured or otherwise fixed into place. Advantages of TVT include the ability to perform the procedure under local anesthesia and on an outpatient basis. Through an anterior vaginal wall incision, small subepithelial tunnels are made bilaterally to the descending pubic rami using sharp dissection. A specialized conical metal needle coupled to a handle is used to drive one end of the sling through the perineal membrane, space of Retzius, and through one of two small suprapubic stab incisions. After bringing up the other end of the tape through the other side, the bladder is filled and intraoperative cough testing is used to set the position of the mesh relative to the undersurface of the urethra. The 5-year cure rate of TVT for stress incontinence is 85%. Risks of the procedure include visceral injury from blind introduction of the needle, voiding dysfunction, and delayed erosion of mesh into the bladder or urethra.

Collagen Bulking agent injection is indicated for patients with urodynamically proven stress incontinence that meets criteria for intrinsic sphincter deficiency but is negative for urethral hypermobility by cotton swab testing. Polytetrafluoroethylene (PTFE) was first used as a periurethral bulking agent in the early 1970s, following which glutaraldehyde cross-linked (GAX) bovine dermal collagen was introduced in 1991, and has since become the most widely used injectable. Use of other materials, including silicone polymers (Macroplastique) and carbon-coated zirconium beads (Durasphere), also has been described. Anesthesia for injection is easily obtained by using intraurethral 2% lidocaine jelly and/or transvaginal injection of the periurethral tissues with 5 mL of 1% lidocaine. A transurethral or periurethral technique may be used, using a 30 degree operating female cystourethroscope to directly visualize the injection. The material is injected underneath the urethral mucosa at the bladder neck and proximal urethra, usually at the 4 and 8 o’clock positions, until mucosal apposition is seen. Prior to injection, patients must demonstrate a negative reaction to a collagen skin test. The long-term cure rate is 20 to 30%, with an additional 50 to 60% of patients demonstrating improvement. Repeat injections

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are frequently necessary because of migration and dissolution of the collagen material.

Surgical Complications The most common complication of incontinence surgery is voiding dysfunction. Complete urinary retention may be transient or permanent, depending on the procedure and the way it is performed. There is also a spectrum of voiding difficulties related to partial urethral obstruction. Because of the 1 to 3% risk of injury to bladder or ureters, intraoperative evaluation of the urinary tract is recommended whenever incontinence surgery is performed. Other potential complications include urinary tract infection, retropubic hemorrhage or abscess, intestinal tract injury, ilioinguinal or other nerve injury, enterocele formation, foreign-body complications caused by graft materials, and inflammatory or infectious processes involving the pubic bones.

BENIGN TUMORS Ovarian Tumors Nonneoplastic Cysts By definition, a cystic enlargement of the ovary should be at least 2.5 cm in diameter to be termed a cyst.

Follicular Cysts. These are unruptured, enlarged graafian follicles. They grossly resemble true cystomas. They can rupture, causing acute peritoneal irritation, undergo torsion and infarction of the ovary or infarction of the tube and ovary, or spontaneously regress.

Corpus Luteum Cysts. These cysts may become as large as 10 to 11 cm. They can rupture and lead to severe hemorrhage and, occasionally, to vascular collapse from blood loss. The symptoms and physical findings of these cysts mimic those of ectopic pregnancy, and they are occasionally associated with delayed menses and spotting. Endometriomas. These account for most “chocolate cysts” and are cystic forms of endometriosis of the ovary. Wolffian Duct Remnants. These are not ovarian cysts but often cannot be distinguished clinically from tumors of the ovary. They are small unilocular cysts. Occasionally, they enlarge and can twist and infarct. In most instances, they are incidental findings at laparotomy and cause no difficulties or symptoms. Mullerian ¨ Duct Remnants. These can appear as paraovarian cysts or as small cystic swellings at the fimbriated end of the fallopian tube (hydatids of Morgagni). Nonfunctioning Tumors Cystadenomas. Serous cystadenomas appear as cysts within translucent walls containing clear fluid and lined by simple ciliated epithelium. They frequently are on a pedicle and may undergo torsion leading to pain and infarction. When encountered surgically, they are adequately treated by simple salpingo-oophorectomy. Many fluid-containing cystic tumors of the ovary are also accompanied by papillary projections and are known as papillary serous cystadenomas. Because of epithelial variation in these tumors, it is often difficult to be sure where they fit in the spectrum of benign to malignant disease. A similar problem of malignant potential exists for the mucinous cystadenoma, which is a cystic tumor containing sticky, gelatinous material. These mucinous tumors are less likely to be malignant than the serous cystadenomas. Approximately 20% of

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the serous tumors and 5% of the mucinous tumors are bilateral. It is not always possible to be sure by gross inspection whether cystic tumors with solid components are benign or malignant. It is usually necessary to excise the involved ovary completely, even though there is no definite evidence of malignancy. The malignant potential of the cystadenoma is then determined by histologic examination. Some cystadenomas are classified as borderline tumors, or tumors of low malignant potential. These (grade 0) carcinomas usually are associated with an excellent prognosis and, if they are unilateral, may be treated by unilateral adnexectomy for women in their reproductive years. Frozen-section examination of the tumor at the time of surgical intervention is necessary to determine the proper course of therapy for patients in the reproductive age group. The opposite ovary should be inspected. Occasionally, a condition known as pseudomyxoma peritonei is encountered; this is a locally infiltrating tumor composed of multiple cysts containing thick mucin. These tumors arise either from ovarian mucinous cystadenomas or from mucoceles of the appendix, both of which commonly coexist. Histologically, they are benign, but by local spread and infiltration they compromise surrounding vital structures. Localized tumors should be excised completely, if possible. Both ovaries and the appendix are removed, even though they grossly appear to be normal.

Mature Teratoma. These germ cell tumors are thought to arise from the totipotential germ cells of the ovary. The tumors often contain calcified masses, and, occasionally, either teeth or pieces of bone can be seen on abdominal radiographs. Mature teratomas occur at any age but are more frequent in patients between 20 and 40 years old. They are benign dermoid cysts. The occasional solid teratoma is usually malignant (immature teratoma). If a teratoma (dermoid) is encountered in a young woman, it is preferable to shell it out from the ovarian stroma, preserving functioning tissue in the affected ovary. Usually these cysts contain ectodermal, mesodermal, and endodermal tissues, in addition to a thick, greasy, fatty material. If this material is spilled during surgery, a chemical peritonitis may result; therefore, it is important to remove these tumors intact. The opposite ovary should be inspected, but no further operative procedure is performed if the opposite ovary appears normal. In approximately 12% of patients, these tumors are bilateral. In patients of childbearing age, some functional ovarian tissue should be preserved. Immature teratomas are treated as other malignant germ cell tumors, with conservative resection and appropriate adjuvant chemotherapy. Brenner Tumor. These are rare epithelial tumors that usually do not secrete hormones. Histologically, the epithelial elements are similar to Walthard rests and are believed to arise from them. These tumors occur primarily in later life and have a small malignant potential. Simple oophorectomy is usually sufficient therapy, and the prognosis is excellent. Meigs’ Syndrome. This pertains to ascites with hydrothorax, seen in association with benign ovarian tumors with fibrous elements, usually fibromas. It is more common to see fluid accumulation with ovarian fibromas that are more than 6 cm in size. The cause of the condition is unknown, but the ascitic fluid may originate from the tumor, as a result of lymphatic obstruction of the ovary. Frequently, this clinical picture is encountered with other ovarian tumors, especially ovarian malignancies, which can produce a cytologically benign pleural effusion; in such cases, it is termed a pseudo-Meigs’ syndrome. Meigs’ syndrome can be cured by excising the fibroma.

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Functioning Tumors Granulosa Cell. Theca Cell Tumor. Pure theca cell tumors (thecomas) are benign, but those with granulosa cell elements may be malignant. It is often impossible to predict their behavior from the histologic features, and prolonged follow-up is necessary in order to judge the nature. Usually, granulosa cell tumors elaborate estrogen, but some of these tumors have no hormone production. In young girls, they are characteristically manifested by isosexual precocity, and in elderly women, they are sometimes associated with postmenopausal bleeding or endometrial carcinoma. The tumor can occur at all ages from childhood to the postmenopausal period, but it is most common in later life, with maximal occurrence between the ages of 40 and 60 years. If the tumor is discovered in the reproductive years and confined to one ovary without signs of surface spread or dissemination, a simple oophorectomy may be sufficient therapy. If it is discovered in later life, removal of both ovaries with the uterus is indicated. These tumors produce inhibin, which may be measured in the peripheral circulation.

Sertoli-Leydig Cell Tumors (Arrhenoblastomas). These rare, but potentially malignant, tumors are associated with androgen output and masculinization. Rarely, they elaborate estrogen. They usually occur in the reproductive age group and appear to contain tubular structures as well as Leydig-type cells. In young patients with a single involved ovary, unilateral oophorectomy is adequate therapy, provided there is no extension of the tumor. For older patients or for those with bilateral involvement, total hysterectomy and bilateral salpingo-oophorectomy are performed.

Struma Ovarii. This term refers to the presence of grossly detectable thyroid tissue in the ovary, usually as the predominant element in dermoid cysts. This tissue occasionally may produce the clinical picture of hyperthyroidism and is rarely malignant. Uterine Tumors Leiomyomas Uterine leiomyomas are the most common benign tumor in the female pelvis. It is estimated that up to 50% of all women at some time in their life have one or more of these uterine tumors. The tumor is never seen before menarche, it grows during reproductive life, and it generally regresses following menopause. The tumors significantly complicate pregnancy by virtue of their rapid growth secondary to the response to pregnancy hormones. Many leiomyomas are asymptomatic; when they do produce symptoms, they cause pain, abnormal uterine bleeding, infertility, ureteral obstruction, bladder distortion, and pressure symptoms secondary to the enlarged uterus. Uterine leiomyomata are subject to a number of degenerative changes, including calcification, necrosis (occasionally with liquefaction), fatty degeneration, and, occasionally, sarcomatous change. Malignant degeneration occurs in less than 1% of all tumors. Uterine myomas may be found in a number of locations within the uterus (Fig. 40-12). The most common location is intramural, but tumors frequently are found just below the peritoneum and occasionally as a pedunculated mass attached to the uterus. Other tumors grow into the endometrial cavity, where they are pedunculated on occasion, prolapsing through the cervix.

Treatment. Most symptomatic tumors can be managed expectantly. When symptoms indicate surgical treatment, consideration must be given to the age of the patient, the number of children she desires, the patient’s age, and her reaction to possible loss of

Intramural Intercavitary Subserous

Pedunculated Submucous Prolapsed

FIG. 40-12. Types of uterine myomas.

reproductive and menstrual function. Surgery should be fitted to the needs and desires of the patient. Therapeutic options may include myomectomy, total abdominal hysterectomy, or transvaginal hysterectomy. Pedunculated myomas are the easiest to remove because the stalk of the tumor is simply ligated or coagulated and the tumor separated from the uterus. Pedunculated tumors in the endometrial cavity often can be removed with the operative hysteroscope. Similarly, tumors projecting from the external wall of the uterus into the peritoneal cavity can be removed laparoscopically by ligating the tumor pedicle and then morcellating the tumor intraperitoneally for removal or removing the tumor through a cul-de-sac incision. Most myomectomies will be performed transabdominally. The most common indication for abdominal myomectomy is the presence of myomas that cause pain, bleeding, or infertility in a patient who continues to desire pregnancy. Before performing myomectomy, the patient must be evaluated completely and counseled about the risk of operation. Blood loss associated with myomectomy frequently exceeds that of hysterectomy. The patient should be advised of the possibility of hysterectomy in the event that myomectomy cannot be effectively performed. It is wise to set aside two or more units of autologous blood for possible operative use. The patient’s tubal status should be evaluated with a hysterosalpingogram, and the patient’s sexual partner should be evaluated with a semen analysis. In the presence of a very large tumor, chemoreduction of the tumor is currently being performed using a GnRHa, such as nafarelin, given by nasal inhalation for a period of 3 months, or leuprolide acetate given intramuscularly every month for 2 months. These agents will cause the tumor to regress in size, and in most cases, provide for less blood loss at the time of operation.

Adenomyosis Adenomyosis is a growth of endometrial tissue in the myometrium of the uterus and is sometimes referred to as endometriosis of the uterine corpus. The condition occurs primarily during reproductive years and leads to a thickening of the myometrial wall with subsequent uterine enlargement. Adenomyosis usually occurs in women who have had a number of pregnancies. Occasionally, patients with adenomyosis will complain of dysmenorrhea, and some present with increased uterine bleeding and heavy menstrual flow. However, a number of patients with adenomyosis in hysterectomy specimens have been asymptomatic. Therefore, the association of

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adenomyosis with heavy menstrual bleeding and dysmenorrhea is questionable.

MALIGNANT TUMORS

Polyps

Ovarian Carcinoma

Endometrial polyps can occur at any time after puberty. A polyp is a local hyperplastic growth of endometrial tissue that usually causes postmenstrual or postmenopausal bleeding or staining, which is cured by polyp removal or curettage. The polyps are usually benign, but cases of adenocarcinoma of the endometrium arising in a polyp have been reported.

Ovarian carcinomas are divided histologically into epithelial, germ cell, and stromal malignancies. The majority of the 27,000 or more cases of ovarian cancer diagnosed annually in the United States are of the epithelial type. The median age at diagnosis for epithelial ovarian cancer is 61 years, and the overall 5-year survival rate for epithelial cancers is 37%. Approximately 15,000 women die of this disease in the United States annually. Although the etiology of ovarian cancer is uncertain, approximately 5% of patients with epithelial tumors come from families where one or more first-degree relatives also have the disease. In such families, prophylactic oophorectomy may be considered at the completion of childbearing, especially if specific BRCA1 or BRCA2 mutations are identified. Testing for these mutations is now readily available in the United States. Primary peritoneal carcinomatosis has been reported in women who have undergone prophylactic surgery, however. Life-long screening with CA 125 levels, pelvic examination, and vaginal ultrasonography of women from affected families is important. Table 40-2 outlines the International Federation of Gynecology and Obstetrics (FIGO) staging system for ovarian cancer. Early lesions are largely asymptomatic, and advanced tumors may produce only nonspecific symptoms such as early satiety, abdominal distention, and vague gastrointestinal symptoms. Although an annual

Cervical Lesions Cervical polyps cause the same symptoms as endometrial polyps. Because they are often quite small and are visible at the external os, they often can be removed as an outpatient procedure followed by cauterization of the base of the polyp. Nabothian cysts are mucous inclusion cysts of the cervix. They are occasionally associated with chronic inflammation and can be removed easily with a cautery. They are harmless, usually asymptomatic, and generally do not require surgery. During reproductive years, the portio of the cervix is covered primarily with glycogenated squamous epithelium, and columnar epithelium is normally found centrally near the external os in most women. This exposed columnar epithelium, termed ectropion or eversion, is usually bright red. Unless accompanied by inflammation and a purulent discharge (cervicitis), it requires no treatment. During adult life, the columnar epithelium is usually replaced by squamous metaplasia, and this physiologic process occurs in the transformation zone at the interface of squamous and columnar epithelium. After menopause, the squamous columnar junction is usually in the endocervical canal.

Vulvar Lesions The term leukoplakia is often used for any white patch of the vulva; it is properly reserved for areas that show histologically atypical epithelial activity. These alterations may precede the development of malignant changes. In many instances, chronically irritated and itchy white areas of the vulva will show sclerosing atrophy of the skin (lichen sclerosus). Lichen sclerosus is a pruritic lesion that does not appear to be premalignant. Hyperplastic lesions termed hypertrophic dystrophies are found that may be benign (epithelial hyperplasia) or that may show atypia, in which case dysplastic changes can be observed. The pruritic symptoms can be helped by topical application of corticosteroids. Testosterone or clobetasol ointment also has been beneficial, especially for the atrophic changes of lichen sclerosus. Noninvasive malignant change of the surface squamous epithelium of the vulva occurs in the same way as that described for the cervix. Carcinoma in situ of the vulva both histologically and clinically behaves like carcinoma in situ of the cervix. The changes are confined to the squamous elements of the vulva, and the condition is sometimes referred to as Bowen’s disease. In certain instances, the apocrine glandular elements of the vulva are involved in association with an intensely pruritic area. Histologically, large, foamy Paget’s cells are seen, similar to those noted in the breast, although invasive carcinoma occasionally can accompany Paget’s cells. Bowen’s disease, and usually Paget’s disease, are considered part of the carcinoma in situ complex of the vulva; they are adequately treated by wide local surgical excision (simple vulvectomy). The laser also is used to treat these lesions locally.

Ovarian Tumors

Table 40-2 FIGO (1986) Staging System for Ovarian Cancer Stage

Characteristic

I IA

Growth limited to the ovaries Growth limited to one ovary; no ascites; no tumor on the external surfaces, capsule intact Growth limited to both ovaries; no ascites; no tumor on the external surfaces, capsule intact Tumor either stage IA or stage IB but with tumor on the surface of one or both ovaries, or with capsule ruptured, or with ascites containing malignant cells or with positive peritoneal washings Growth involving one or both ovaries on pelvic extension Extension or metastases to the uterus or tubes Extension to other pelvic tissues Tumor either stage IIA or IIB with tumor on the surface of one or both ovaries, or with capsule(s) ruptured, or with ascites containing malignant cells or with positive peritoneal washings Tumor involving one or both ovaries with peritoneal implants outside the pelvis or positive retroperitoneal or inguinal nodes; superficial liver metastases equals stage III; tumor is limited to the true pelvis but with histologically verified malignant extension to small bowel or omentum Tumor grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces Tumor of one or both ovaries; histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes negative Abdominal implants greater than 2 cm in diameter or positive retroperitoneal or inguinal nodes Growth involving one or both ovaries with distant metastases; if pleural effusion is present, there must be positive cytologic test results to allot a case to stage IV; parenchymal liver metastases equals stage IV

IB IC

II IIA IIB IIC

III

IIIA IIIB IIIC IV

source: From the International Federation of Gynecology and Obstetrics.

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pelvic examination is valuable in detecting early ovarian cancer, efforts to establish other cost-effective screening programs using serum markers such as CA 125 and vaginal ultrasound examination are being developed. Vaginal ultrasound is a promising technology that is not presently cost-effective in mass screening programs, because the yield is no more than 1 ovarian cancer per 1000 asymptomatic postmenopausal women screened. Currently, the more than 70% of women with epithelial cancer have stage III tumors at the time of diagnosis. Widespread peritoneal dissemination, omental involvement, and ascites are the rule, rather than the exception, in these women.

Treatment. In general, therapy for epithelial ovarian cancer consists of surgical resection and appropriate staging followed by adjuvant radiation or chemotherapy. Women with low-grade early stage (IA or IB) cancers who have undergone appropriate surgical staging may be treated with surgery without adjuvant therapy. If the lesion is bilateral (stage IB), abdominal hysterectomy and bilateral salpingo-oophorectomy are sufficient. It is in the limited group of patients with unilateral histologic grade 1 or 2 lesions that fertility can be preserved by performing adnexectomy and staging biopsies without removing the uterus or contralateral ovary and fallopian tube. In all other patients (stage IA, grade 3, and stage IC and above), appropriate initial surgery includes bilateral salpingo-oophorectomy, abdominal hysterectomy if the uterus has not been removed on a prior occasion, appropriate staging, and tumor resection. Staging. Staging indicates surgical resection or biopsy of all potential areas of tumor spread. Thorough staging is imperative in determining appropriate treatment for patients with ovarian cancer. Among patients whose cancer is confined to one or both ovaries at the time of gross inspection, occult metastases can be identified by careful surgical staging in one-third. If staging is improperly performed and adjuvant therapy omitted in patients whose tumors are apparently confined to the ovary, 35% will suffer preventable relapse. Epithelial ovarian cancers disseminate along peritoneal surfaces and by lymphatic channels. The first site of spread is the pelvic peritoneum. Later the abdominal peritoneal surfaces and diaphragms are involved. The omentum is a common site for metastases, as are both the para-aortic and pelvic lymph nodes. Because the abdominal cavity in its entirety is not accessible through a transverse pelvic incision, it is paramount that surgery for ovarian malignancies be performed through a full-length midline abdominal incision. After the peritoneal cavity is entered, the visceral and parietal surfaces are inspected for metastatic disease, and any suspicious areas are biopsied. If ascites is present, it should be aspirated and heparinized. Cytologic evaluation for metastatic cells or clusters is then performed. If no ascites is found, peritoneal washings with balanced salt solution or lactated Ringer’s solution are obtained from the abdominal cavity and submitted for cytologic evaluation after centrifugation and fixation. Appropriately staged patients with histologic grade 1 or grade 2 tumors confined to one or both ovaries (stage IA or IB) require no postoperative therapy. Five-year survival in this group of patients exceeds 90%. Those patients who have stage I, grade 3 lesions, stage IC tumors (malignant peritoneal washings, rupture of tumor, surface excrescences, or ascites), or stage II cancers that are completely resected may be treated equally well with systemic chemotherapy, radiotherapy of the whole abdomen, or a single instillation of intraperitoneal

radioactive chromic phosphate. Five-year survival approaches 75% in this group of patients. Women with stages III and IV disease require systemic chemotherapy with cisplatin or carboplatin, generally in combination with a taxane such as paclitaxel. Survival at 5 years in such patients may exceed 20%, although this rate drops as low as 10% at 10 years. Survival in advanced ovarian cancer is influenced by a number of factors, such as patient age, the histologic type and grade of the lesion, the presence or absence of ascites, and the type of chemotherapy employed. Of prime importance in advanced-stage disease, however, is the volume of tumor remaining after the initial surgical procedure. Many patients with stages III and IV ovarian cancer have diffuse peritoneal, retroperitoneal, diaphragmatic, and mesenteric metastases that resist complete surgical resection. It is often possible, however, to remove large amounts of peritoneal tumor by entering the retroperitoneal spaces and freeing the disease-laden surfaces from the underlying viscera. It is widely accepted that patients in whom little or no residual disease remains after initial operation, on average, live longer than those in whom a great deal of tumor remains unresected. The terms debulking and cytoreduction indicate aggressive surgical removal of ovarian cancer. When disease remaining after surgical resection consists of nodules or plaques less than 1 to 2 cm in diameter, the surgical effort is termed optimal, and when a larger volume of residual disease remains, the surgical removal is termed suboptimal. Because of the survival advantage, every effort should be made to resect as much disease at the time of diagnostic laparotomy as is possible. Because many patients with advanced ovarian cancer are elderly and nutritionally depleted, surgical enthusiasm must be tempered by proper preoperative evaluation and support with appropriate central monitoring and hyperalimentation where indicated. Occasionally, it is more prudent to obtain confirmation of the diagnosis, treat with systemic chemotherapy, and then perform definitive surgery when the tumor has diminished in size and the patient has been nutritionally resuscitated. Resection of nodules involving the small or large bowel is warranted if the exercise results in complete removal of all observed disease. Such procedures are probably not indicated if tumor remains at other sites. After surgical extirpation of the tumor, patients with suboptimal ovarian cancers must be treated with chemotherapy. Approximately 80% of these tumors will respond to platinum-based combination therapy; 40% of all patients will experience a complete response, or complete resolution of tumor identified on physical examination or radiographic or serologic study.

Resection of Advanced Ovarian Cancer. When advanced ovarian carcinoma is discovered at the time of exploratory laparotomy, the first reaction is often one of resignation. There has been a tendency to perform a diagnostic biopsy and close the abdomen without further surgical intervention. In experienced hands, however, successful reduction of tumor volume to nodules 2 cm or less is possible in at least 50% of women with advanced ovarian cancer. If the primary surgeon is incapable of obtaining such results, the patient should be referred to one with sufficient expertise in this area. Survival following chemotherapy is inversely related to the volume of residual disease at the time of primary surgery. Several techniques ensure adequate resection. First, most ovarian cancer is found on peritoneal surfaces and not invading viscera. A retroperitoneal approach thus facilitates mobilization of the involved mesothelium. The lateral aspects of the paracolic gutters may be incised and dissection carried medially to undermine tumors in these

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locations. The ovarian artery and vein should be identified at this point and securely ligated before division. Once the blood supply to the main body of the ovarian tumor is secured, the adnexa may be mobilized more easily. It is often useful to dissect the ureter from the underlying pelvic peritoneum and retract it laterally with a vessel loop. This allows access to the lateral pelvic peritoneum. Tumor nodules on anterior and posterior cul-de-sac peritoneum may be resected by developing planes in the retroperitoneal spaces and isolating the disease from the underlying bladder, sigmoid colon, and ureters. Opening the pararectal and paravesical spaces facilitates this dissection and also allows access to the uterine vessels, which then may be clamped, ligated, and divided. When the hysterectomy and adnexectomy are complete, the omentum may be resected. Disease on the right diaphragm may be resected by transecting the falciform ligament and retracting the liver inferiorly. If it serves to remove all remaining tumor, splenectomy may be performed. Resection of small and large bowel may be performed if the operation removes all residual disease. Use of the ultrasound aspirator and argon beam coagulator have resulted in an increased ability to completely remove tumors, including those that are implanted on the serosal surfaces and mesentery of the bowel. With diligence it is often possible to remove all appreciable disease with these instruments.

“Second-Look” Operations “Second-Look” Laparotomy. Ovarian cancer often defies diagnosis because it does not produce symptoms and is detectable neither radiographically nor serologically, even in relatively advanced stages. The assessment of ovarian cancer during and after therapy is similarly difficult. Although CT or MRI may identify masses as small as 2 to 3 cm in diameter, neither technique can reliably detect smaller masses, much less the miliary spread so often identified in advanced ovarian cancer. CA 125 is more sensitive than radiographic or magnetic scanning, but is also associated with a number of false-positive results and may not be elevated in patients with mucinous tumors. In addition, approximately half of patients with advanced ovarian cancer whose CA 125 levels normalize during chemotherapy harbor viable and clinically undetectable disease. Radiolabeled monoclonal antibodies raised against epithelial tumor surface antigens may be more sensitive than traditional methods but remain to be proven effective. The practice of performing exploratory surgery following chemotherapy originated during a time when alkylating agents were used almost exclusively. Because acute nonmyelocytic leukemia is associated with prolonged administration of such agents, a “secondlook” operation was performed at an interval of 12 to 24 months following primary surgery so that treatment could be stopped in women with no disease. Presently, the duration of postoperative combination chemotherapy is often only 5 to 6 months, and the risk of leukemia is very low. In approximately 20 to 30% of patients who receive such treatment, no cancer will be identified at the time of a second operation. These patients have an excellent long-term prognosis. In women who have persistent microscopic disease, the prognosis is also favorable, and in those with persistent gross tumors, the prognosis is relatively poor. Second-look surgery is currently used primarily as a research tool. New treatment regimens can be evaluated quickly by performing a second-look operation, because the findings at such an operation reflect the ultimate clinical outcome and hence the value of the treatment regimen. Second-look surgery is also valuable in determining when therapy can be discontinued and when

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further treatment is indicated. There is no known survival benefit from second-look surgery. If a tumor is identified and can be resected, a Tenckhoff catheter may be placed, through which intraperitoneal chemo- or immunotherapy may be given. If no visible disease is present, a silicone drain can be inserted for the postoperative administration of radioactive chromic phosphate. Although the morbidity of secondlook surgery is very low, there is no place for this type of operation in patients who wish or who can physiologically tolerate no further treatment at the conclusion of primary combination chemotherapy. Nor is there any reason to reexplore such a patient without the ability or intention to perform a thorough, deliberate staging procedure that can guide subsequent therapy. Other Secondary Operations. Surgical resection of tumor after chemotherapy or at the time of relapse is termed secondary cytoreduction. In the occasional patient who undergoes diagnostic biopsy only before the administration of chemotherapy, early reexploration may be termed interval cytoreduction. There is evidence that the surgical removal of an extensive tumor is facilitated by the administration of one or two courses of combination chemotherapy. In patients with a massive tumor burden, this approach may not only be safer, but also might result in a more successful tumor resection before the completion of chemotherapy. It also promotes the early administration of intraperitoneal chemotherapy. The importance of secondary cytoreduction is not clearly established. In patients with relapsing ovarian cancer, the prognosis depends in part on the extent of the tumor and in part on the type of response to previous therapy. Also important is the interval between primary therapy and relapse. In those who completely responded to platinum combination treatment and who have a disease-free period exceeding 2 years, resumption of platinum-based chemotherapy is very effective. Paclitaxel therapy may be effective in similar situations. It is in such patients that surgical removal of the recurrent tumor is likely to be the most beneficial. Palliative Surgery. In most cases of advanced ovarian cancer, death is associated with bowel dysfunction or frank obstruction. Although invasion of the small bowel and colon is unusual, growth of the tumor adjacent to the bowel leads to mesenteric compromise and dysfunction usually heralded by distention, nausea, and vomiting. When bowel obstruction occurs early in the clinical course of ovarian cancer, particularly if it occurs before the administration of chemotherapy, surgical intervention is warranted and should be aggressive. Resection or bypass of the involved bowel is indicated; colonic resection also may be indicated. It is important to perform adequate radiographic studies preoperatively so that obstructed small bowel is not decompressed into a compromised colon. When bowel obstruction occurs after chemotherapy, the prognosis is unfavorable. Women who develop such difficulties have a limited survival following surgical correction. Surgery is often difficult to perform because of an extensive tumor. Laparotomy may be complicated by intestinal injury or fistula. Often the best approach in these patients is the use of a percutaneous or endoscopically positioned gastrostomy tube and intravenous fluids or conservative nutritional support. Such a procedure may limit the length of hospitalization and allow the patient to remain in a supportive home environment for a greater period of time. Laparoscopy in Ovarian Cancer. At present, our ability to resect large ovarian cancers successfully using laparoscopic equipment is limited. In the past, efforts to perform second-look procedures through the laparoscope were ineffective when compared with laparotomy. However, with the advent of new equipment and techniques, the role of laparoscopy in the staging and treatment

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of ovarian malignancies may be expanding. Several investigators have developed successful methods of performing both pelvic and para-aortic lymphadenectomies using endoscopic equipment. In addition, ultrasonographic and serologic criteria are evolving that will allow the surgeon to more successfully distinguish between benign and malignant neoplasms of the ovary. Caution must be exercised when dealing with potentially malignant unresected ovarian tumors using the laparoscope.

Tumors of Low Malignant Potential These are epithelial tumors of malignant potential intermediate between benign lesions and frank malignancies. Histologically, most are of the serous type. Although these tumors may be associated with epithelial budding, atypia, mitoses, and stratification, they are distinguished from invasive cancers microscopically by lack of stromal invasion. The median age of diagnosis is approximately 10 years younger than that of patients with epithelial cancers. The vast majority occur in stage I and have a favorable prognosis. Surgery should include abdominal hysterectomy and bilateral salpingo-oophorectomy unless fertility is to be preserved in patients with unilateral lesions. These patients may undergo unilateral salpingo-oophorectomy. Ovarian cystectomy or nonextirpative resections commonly result in recurrences. Patients with stages III and IV lesions have 5-year survival rates that approach 85% after complete surgical resection. There is little evidence that either chemotherapy or radiotherapy administered after surgery improves survival; on the other hand, deaths from chemotherapy-induced leukemia are not uncommon.

Germ Cell Tumors These tumors occur in women in the first three decades of life and typically grow rapidly, producing symptoms of distention and abdominal fullness. Torsion may occur, producing an acute abdomen. Most are unilateral, and all have a tendency to spread to the paraaortic lymph nodes, as well as throughout the peritoneal cavity. Although they are similar in many ways to testicular cancer in the male, there are some differences. Dysgerminoma, the female equivalent of testicular seminoma, is composed of pure, undifferentiated germ cells. It is bilateral in 10 to 15% of patients and is occasionally associated with elevated levels of hCG or lactate dehydrogenase (LDH). It is the most common ovarian malignancy diagnosed during pregnancy. Patients bearing dysgerminomas should undergo appropriate staging at the time of the primary resection but need not undergo hysterectomy (if fertility is to be preserved) or removal of the opposite ovary if it is normal in appearance. Secondary operations solely for staging purposes are unwarranted. Adjuvant therapy is unnecessary unless there is evidence of extraovarian spread. Either radiotherapy encompassing the whole abdomen or systemic chemotherapy can be given to patients with metastases. This tumor is exquisitely sensitive to either type of treatment, and the cure rate exceeds 90% even in patients with metastases. Chemotherapy has the advantage of preserving ovarian function, whereas radiotherapy results in ovarian failure. The other germ cell tumors, in order of frequency, are immature teratoma; endodermal sinus, or “yolk sac,” tumor; mixed tumors; embryonal carcinomas; and choriocarcinomas. The first may be associated with elevated levels of alpha-fetoprotein (AFP). Elevated AFP levels are found in all patients with endodermal sinus tumors and mixed tumors that contain this component. Embryonal carcinomas are associated with abnormal levels of both AFP and hCG, and choriocarcinomas secrete hCG.

These tumors are invariably unilateral but may spread by peritoneal, hematogenous, or lymphatic routes. Surgical therapy involves unilateral oophorectomy and appropriate staging. Except for those with completely resected stage I, grade 1 immature teratomas and those with stage I dysgerminoma, all patients with germ cell tumors require systemic chemotherapy. Three courses of a platinum and etoposide-containing combination suffice in those patients whose tumors are completely resected. Cure rates in these patients approach 90%. In women with incompletely resected nondysgerminomatous germ cell tumors, cure may still be expected in more than 50%, but prolonged chemotherapy may be necessary. These tumors are not sensitive to radiotherapy.

Carcinoma of the Cervix Carcinoma of the cervix accounts for about 16,000 cases and 5000 deaths annually in the United States. Risk factors include multiple sexual partners, early age at first intercourse, and early first pregnancy. DNA related to that found in the human papillomavirus has been identified in cervical dysplasia and carcinoma in situ, both precursor lesions, as well as in invasive cancers and lymph node metastases. Cigarette smoking is highly associated with an increased risk of cervical cancer and may impair the activity of T lymphocytes. In no other cancer has widespread screening had as profound an impact on mortality as it has in carcinoma of the cervix. Georges Papanicolaou developed the cytologic smear that bears his name in 1943. Since then, screening programs have dramatically reduced the rate of invasive cervical cancer in countries where this test is widely available. Use of the Papanicolaou (Pap) smear has shifted the frequency of cervical abnormalities toward the premalignant intraepithelial diseases, dysplasia, and carcinoma in situ. Although there are histologic grades of dysplasia leading to carcinoma in situ, all intraepithelial lesions are noninvasive and can be treated successfully using conservative methods. Eighty percent of all cervical cancers are squamous cell in type and arise from the squamocolumnar junction of the cervix. This epithelial transition zone is found on the face of the cervix or ectocervix in adolescence, and, through a process of squamous metaplasia, gradually moves into the endocervical canal as menopause is passed. Dysplasia represents a disordered metaplasia and gives rise to epithelial cells that contain increased mitotic rates and nuclear atypia and that lack appropriate maturation within the epithelium. Identification and eradication of intraepithelial lesions before invasion can occur are the goals of cervical cancer screening. The remainder of cervical malignancies arise in the endocervical canal and are either adenocarcinomas or adenosquamous carcinomas. Although adenocarcinomas are very similar in their clinical behavior to squamous cancers, there is some evidence that adenosquamous cancers are more aggressive. Other rare histologic varieties associated with poor prognosis are neuroendocrine small cell carcinomas and clear cell cancers. The latter are frequently associated with maternal exposure to diethylstilbestrol.

Staging Cervical cancers spread predominantly by lymphatic channels. The first lymph nodes involved are those in the tissues immediately lateral to the cervix. This region is referred to as the paracervical or parametrial area. The next lymph nodes to be involved, in order, are those in the obturator fossa, the internal and external iliac chain, the common iliac chain, and the para-aortic lymph nodes. Direct vaginal extension may occur. The lymph nodes in the presacral area may be

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Table 40-3 FIGO Staging System for Cervical Cancer Stage

Characteristic

0 I

Carcinoma in situ The carcinoma is strictly confined to the cervix (extension to the corpus should be disregarded) Preclinical carcinomas of the cervix; that is, those diagnosed only by microscopy Minimal microscopically evident stromal invasion Lesions detected microscopically that can be measured. The upper limit of the measurement should not show a depth of invasion of more than 5 mm taken from the base of the epithelium, either surface or glandular, from which it originates, and a second dimension, the horizontal spread, must not exceed 7 mm. Larger lesions should be staged as IB Lesions of greater dimensions than Stage IA2 whether seen clinically or not. Preformed space involvement should not alter the staging but should be specifically recorded so as to determine whether it should affect treatment decisions in the future Tumor size no greater than 4 cm Tumor size greater than 4 cm Involvement of the vagina but not the lower third, or infiltration of the parametria but not out to the sidewall Involvement of the vagina but no evidence of parametrial involvement Infiltration of the parametria but not out to the sidewall Involvement of the lower third of the vagina or extension to the pelvic sidewall Involvement of the lower third of the vagina but not out to the pelvic sidewall if the parametria are involved Involvement of one or both parametria out to the sidewall Obstruction of one or both ureters on intravenous pyelogram (IVP) without the other criteria for stage III disease Extension outside the reproductive tract Involvement of the mucosa of the bladder or rectum Distant metastasis or disease outside the true pelvis

IA IA1 IA2

IB

IB1 IB2 II IIA IIB III IIIA IIIB III (urinary) IV IVA IVB

source: From the International Federation of Gynecology and Obstetrics.

involved in early stage lesions, and the supraclavicular lymph nodes are the most common site of distant nodal metastases. FIGO staging for cervical cancer is based on clinical examination, intravenous pyelography, and chest radiography. CT or MRI findings do not affect the clinical stage. Table 40-3 illustrates the FIGO staging system. Note that the presence of hydronephrosis connotes stage IIIB even if there is no clinical evidence of extracervical spread. Except for selected patients with stage IVA lesions and those with distant metastases, all patients with stage IIB cancer and above are treated primarily with radiotherapy in the United States.

Treatment Intraepithelial or Preinvasive Disease. Abnormal Pap smears must be evaluated by colposcopy and biopsy. Colposcopy is the examination of the cervix with a low-power (x10 to 50) microscope after application of dilute acetic acid to the cervix. The acid solution is mucolytic and serves to desiccate the epithelium, a process that brings out subtle epithelial patterns referred to as white epithelium, punctation, mosaicism, and abnormal vasculature. Abnormal areas must undergo mechanical biopsy or wide excision with

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a wire loop electrode and are examined histologically. If loop excision is not performed, the endocervical canal should be curetted to exclude epithelial abnormalities in this area, which is difficult to visualize colposcopically. Once the diagnosis of an intraepithelial process is made and stromal invasion excluded, local therapy can be performed. If there are abnormal cells on the endocervical curettage specimen, a diagnostic cone biopsy or loop electrosurgical excision procedure (LEEP) is indicated to exclude the possibility of an invasive or microinvasive lesion in the endocervical canal. Cervical intraepithelial neoplasia is treated in a number of ways. In general, the larger the lesion and the higher the grade of dysplasia, the greater the failure rate. Similarly, more aggressive therapy yields lower failure rates at increased risk of complications. The most definitive treatment for cervical intraepithelial neoplasia is vaginal or abdominal hysterectomy. This operation is associated with a rate of subsequent dysplasia at the vaginal apex of 1 to 2%. This major operation is usually reserved, however, for patients with extensive or high-grade lesions, those with recurrent disease after conservative treatment, those in whom adequate follow-up is unlikely, and those with other indications for hysterectomy, such as prolapse, abnormal uterine bleeding, pain, or a pelvic mass. Cervical cone biopsy is curative in most cases of cervical intraepithelial neoplasia. In patients in whom the surgical margins of the cone specimen are uninvolved, the risk of recurrence is less than 5%. If the surgical margins are involved, half of such patients will develop recurrent disease. This is an outpatient procedure and associated with few serious risks. It may, however, require general anesthesia. More conservative methods of treating cervical intraepithelial neoplasia include wire loop excision, laser vaporization, and cryosurgery. Loop excision can be done under local anesthesia (paracervical block) in the outpatient setting. The advantage of loop excision is that it removes the diseased area and provides a diagnostic biopsy specimen. The main disadvantage is the relatively large amount of cervical stroma that is taken with the involved epithelium. In cases of cervical intraepithelial neoplasia confined to the ectocervix, such deep excision is probably unnecessary. Laser vaporization is usually performed with a carbon dioxide laser, but other laser instruments may be used. The ectocervical transformation zone is ablated to a depth of about 7 mm to ensure the removal of endocervical glandular epithelium. This is a convenient outpatient procedure that results in a clearly visible squamocolumnar junction at the site of treatment. Risks of bleeding and infection are small. Cryotherapy is an inexpensive outpatient procedure that produces a frostbite injury to the ectocervical epithelium. When the cervix reepithelializes, the dysplasia generally does not recur. This is a simple technique that should not be applied to patients with endocervical lesions. The main disadvantage of cryotherapy is obliteration of the squamocolumnar junction, making subsequent colposcopic examination somewhat difficult. In patients with very localized mild dysplasias or low-grade cervical intraepithelial neoplasia, local excision or electrocautery may be sufficient to eradicate the disease.

Microinvasive Cervical Cancer. FIGO (see Table 40-3) subdivides microinvasive cancers into those with “early” invasion (stage IA1 ) and those in which the tumor measurements are less than 5 mm in thickness and 7 mm in lateral extent (stage IA2 ). This aspect of the FIGO staging system for cervical cancer fails to distinguish adequately between stages IA2 and IB, however, because both may have occult lymph node metastases requiring regional therapy.

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Many prefer the original system of the Society of Gynecologic Oncologists, in which stage IA (microinvasive) tumors may invade to no more than 3 mm and must lack capability of lymphatic space invasion. Stage IB includes all other cancers clinically confined to the cervix, even if they cannot be visualized on examination. The advantage of this system is that it clearly divides stage I cancer into two treatment groups. Few patients with stage IA cervical cancer have metastases to the lymph nodes. Simple, or extrafascial, hysterectomy without lymphadenectomy is therefore adequate therapy. Five-year survival rates approach 100% in these patients. In exceptional patients, cervical cone biopsy or electrosurgical excision may be sufficient treatment, provided close surveillance is possible.

Early Invasive Cervical Cancer (Stages IB and IIA). Stages IB and IIA tumors are associated with a risk of pelvic lymph node metastases of 10 to 15% and a risk of spread to the paraaortic nodes of about 5%. Treatment must include the regional lymph nodes in these patients. Radical hysterectomy with pelvic lymphadenectomy or definitive radiotherapy is effective treatment in this stage cancer. Prognosis with either modality depends on the size of the primary lesion, the presence or absence of lymph–vascular space involvement, spread to the regional lymph nodes, and status of the surgical margins. Women with stage IB2 cervical cancers (exceeding 4 cm in diameter), especially those endocervical primaries that distend the cervix circumferentially, may require a combination of radiotherapy and surgery. These large endocervical tumors are referred to as “barrel” lesions and are refractory to surgery or radiotherapy alone. Isodose curves from cesium sources may not encompass the entire tumor (Fig. 40-13). Cure rates with either treatment may be as low as 50%. One current approach to these tumors is the administration of pelvic radiotherapy followed by a cesium implant and subsequent

FIG. 40-13. Radiotherapeutic isodose curves superimposed on a large stage IB “barrel” lesion of the cervix. The upper margins of the tumor may receive an inadequate dose of radiotherapy.

simple hysterectomy. This technique may reduce the number of patients who have persistent invasive cancer in the cervix after radiotherapy and consequently improve survival. Stage IB1 lesions and early stage IIA cancers may be treated successfully with radical hysterectomy and pelvic lymphadenectomy. This operation was pioneered by John Clark in 1895. Radical surgery was transiently eclipsed by the first use of radium in the treatment of cervical cancer by Sj¨ogren and Stenbeck in 1899, and subsequent establishment of the first radium hospital in Stockholm, Sweden, in 1910. Radical surgery reemerged in the treatment of early carcinoma of the cervix with the advent of the Pap smear and increased diagnosis of early stage tumors in young women. Because early cervical cancer so rarely spreads to the ovaries, radical hysterectomy need not include oophorectomy. Ovarian preservation is one of the strongest arguments for the use of surgery over radiotherapy, because the latter inevitably results in the premature loss of ovarian function.

Locally Advanced Carcinoma of the Cervix (Stages IIB to IVA). These cancers are treated primarily with radiotherapy, with cisplatin as a radiosensitizer. Treatment consists of a combination of external therapy to the pelvis (teletherapy) from a highenergy source such as a linear accelerator and a local dose delivered to the cervix and parametrial tissue (brachytherapy) using a cesium applicator such as a Fletcher-Suite tandem and ovoids (Fig. 40-14). Combination therapy is essential because doses adequate to control cervical tumors exceeding about 1 cm in diameter cannot be given using teletherapy alone. Bladder and rectal tolerances are approximately 6000 rads; higher doses can only be attained by combination therapy. The addition of cisplatin as a weekly radiosensitizer has resulted in improved survival with no apparent increase in toxicity when compared with radiation alone. Cure rates for stage IIB cervical cancers approach 65%, and those for stage IIIB approach 35%. Because the risk of pelvic sidewall

FIG. 40-14. Fletcher-Suite tandem and paired ovoids. Hollow applicators that can be placed in the uterus and vagina and “afterloaded” once the appropriate position and dosimetry are established.

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Colon

Ureter lleum

Right colon

Terminal ileum FIG. 40-16. Indiana continent urinary reservoir based on the right colon and terminal ileum. The ileum is plicated to preserve continence.

FIG. 40-15. “Hockey stick” incision used for retroperitoneal para-aortic lymph node dissection in cases of locally advanced cervical cancer.

lymph node involvement increases with advancing stage, the dose of radiotherapy to this area is advanced with increasing stage. When para-aortic metastases are present in either stage, survival is significantly impaired. Survival for patients with stage IIB carcinoma of the cervix and para-aortic metastases is poorer than that for those with stage IIIB disease and negative para-aortic lymph nodes. Gross para-aortic lymph node metastases may be detected by CT, MRI, lymphangiography, or PET scanning. Microscopic nodal metastases are best detected by retroperitoneal common iliac and paraaortic lymphadenectomy, a relatively simple procedure performed through a “hockey stick” or paramedian incision (Fig. 40-15). The fascial layers are divided, sparing the peritoneum, which is reflected medially to expose the lymph node–bearing areas overlying the major blood vessels. Laparoscopic staging and pelvic and para-aortic lymph node dissection may be used by appropriately trained surgeons. The finding of metastases in the common iliac or para-aortic chain indicates the need for extended-field radiotherapy encompassing these areas in addition to the pelvis. Even with such therapy, 5-year survival rates are low, seldom exceeding 20%. Many consider the presence of para-aortic lymph node metastases to be an indicator of systemic disease, although supraclavicular metastases are present in fewer than 25% of such patients.

Recurrent Cervical Cancer. As a rule, patients who develop local recurrences after primary surgical therapy are treated most effectively with external and internal beam radiotherapy. Although those with lymph node failures may not be curable in this setting, those with vaginal recurrences often can be saved with such an approach. Patients who suffer recurrences at sites distant from the pelvis may be treated with palliative local radiotherapy or chemotherapy with limited success. Women who develop recurrent cancer following primary radiotherapy are generally not candidates for curative therapy. If, however, the recurrent lesion is small, the interval to failure is a year or more, and the lesion is unaccompanied by symptoms such as back or leg pain or edema, surgical resection may be possible. Because

radiotherapy results in fibrosis of the connective tissues surrounding the cervix, radical hysterectomy is impractical. The risk of vesicovaginal or rectovaginal fistulas approaches 50%. In addition, surgical margins may be compromised by limited resection in such a situation. Most gynecologic oncologists prefer to perform pelvic exenteration in such circumstances. Often, an anterior exenteration with en bloc removal of the bladder, cervix, uterus, and upper vagina is feasible. These operations require urinary diversion. Because of radiation exposure, however, an ileal conduit may be associated with urinary leakage from ureteroileal anastomoses. The preferred method of diversion in these patients is the creation of a sigmoid urostomy or transverse colon conduit. Other surgical options include a Koch pouch or the Indiana reservoir (Fig. 40-16), both of which provide a means of urinary continence without an external appliance. In the case of extensive local recurrences, sigmoid resection may be required in addition to removal of the bladder. A total pelvic exenteration is performed. The sigmoid colon may be brought to the skin as a colostomy or reanastomosed to the rectal stump. Pelvic exenterations may be subclassified as supralevator or infralevator depending on whether this muscular diaphragm is broached (Fig. 40-17). Supralevator exenterations are generally associated with less operative morbidity. An infralevator exenteration is required if the tumor involves the middle or lower third of the vagina or the vulva. Vaginal reconstruction in these extensive procedures with gracilis or rectus abdominis myocutaneous flaps is highly satisfactory (Figs. 40-18 and 40-19). In general, about half the patients thought to be candidates for pelvic exenteration are found to have intraperitoneal spread or nodal metastases at the time of exploratory laparotomy, and, in most centers, do not undergo resection. Laparoscopy may be a useful way of excluding such patients from laparotomy. Of the remaining patients in whom surgery is possible, 30 to 50% will develop a second, nearly always fatal, recurrence after surgery. This complex operation should thus be undertaken only in carefully selected patients.

Endometrial Cancer Endometrial cancer is the most common female genital malignancy, accounting for 34,000 cases annually in the United States. It is a

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A

B

FIG. 40-17. Pelvic exenteration may be limited to the supralevator space ( A ) or can extend below the levator ani muscle (shaded area) ( B ).

Gracilis muscle

FIG. 40-18. Development of gracilis myocutaneous flaps.

highly treatable cancer, with approximately only 6000 deaths reported each year. Risk factors for endometrial cancer include obesity, diabetes mellitus, hypertension, low parity, early menarche, and late menopause. Prolonged or unopposed exposure to estrogens is implicated in the genesis of endometrial cancer and its precursor, endometrial hyperplasia. Women who take estrogens in the menopausal years are known to have a sixfold increase in the risk of endometrial cancer if progestational agents are not taken as well. There is also an increase in the incidence of endometrial lesions in women with a history of chronic anovulation (Stein-Leventhal syndrome) and in those with estrogen-producing ovarian stromal neoplasms, such as granulosa cell tumors, and in those who take tamoxifen. Endometrial hyperplasia may be divided into classifications of simple and complex, depending on the microscopic architecture, and into those with or without atypia. These hyperplasias are thought to be estrogen-dependent. Atypical complex hyperplasias are most likely to give rise to frank adenocarcinomas. They occur in women at an average age that is 5 to 10 years younger than those with frank carcinomas. Simple hysterectomy is the preferred method of treatment for the hyperplasias. In women with underlying health problems that preclude surgical therapy, therapy with progestational agents such as megestrol or medroxyprogesterone acetate may be used with success. Careful monitoring with endometrial biopsy or curettage or vaginal ultrasound is required in these patients, however. Both endometrial hyperplasia and carcinoma are often heralded by abnormal perimenopausal or postmenopausal uterine bleeding. This symptom accounts for the early detection and relative curability of these neoplasms.

Treatment FIG. 40-19. Rotation of the flaps inferomedially and creation of a neovaginal tube that is rotated into the pelvic defect.

Endometrial cancer is staged according to the FIGO criteria detailed in Table 40-4. Many patients have stage I disease and can be

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Table 40-4 FIGO (1988) Staging System for Endometrial Cancer Stages

Characteristics

IA G123 IB G123 IC G123 IIA G123 IIB G123 IIIA G123

Tumor limited to endometrium Invasion to 1/2 myometrium Endocervical glandular involvement only Cervical stromal invasion Tumor invades serosa or adnexae or positive peritoneal cytology IIIB G123 Vaginal metastases IIIC G123 Metastases to pelvic or para-aortic lymph nodes IVA G123 Tumor invasion bladder and/or bowel mucosa IVB Distant metastases including intra-abdominal and/or inguinal lymph node Histopathology—Degree of Differentiation Cases should be grouped by the degree of differentiation of the adenocarcinoma: G1 5% or less of a nonsquamous or nonmorular solid growth pattern G2 6%–50% of a nonsquamous or nonmorular solid growth pattern G3 More than 50% of a nonsquamous or nonmorular solid growth pattern Notes on Pathologic Grading Notable nuclear atypia, inapppropriate for the architectural grade, raises the grade of a grade I or grade II tumor by I. In serous adenocarcinomas, clear cell adenocarcinomas, and squamous cell carcinomas, nuclear grading takes precedence. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component. Rules Related to Staging Because corpus cancer is now surgically staged, procedures previously used for determination of stages are no longer applicable, such as the finding of fractional D&C to differentiate between stage I and II. It is appreciated that there may be a small number of patients with corpus cancer who will be treated primarily with radiation therapy. If that is the case, the clinical staging adopted by FIGO in 1971 would still apply but designation of that staging system would be noted. Ideally, width of the myometrium should be measured along with the width of tumor invasion.

managed successfully with abdominal hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy may be required, primarily to reduce the risk of vaginal recurrence. This can be given preoperatively with external therapy or a Fletcher-Suite implant or intrauterine packing (Heyman’s or Simon’s capsules). Some clinicians prefer to deliver radiotherapy postoperatively after the uterus has been evaluated thoroughly. Either external beam therapy or vaginal cesium may be used. Pelvic lymph node metastases occur in about 12% of patients with endometrial cancer apparently confined to the uterus. Lymph node metastases have a significant negative impact on survival. Risk factors associated with lymph node spread include high histologic grade (grade 2 or 3), low levels of progesterone receptor, deep myometrial or lymphatic channel invasion, spread to the adnexa, endocervical extension, and unusual histologic variants, such as papillary serous or clear cell carcinomas. It may be unnecessary to perform lymph node sampling in patients with grade 1 adenocarcinomas confined to the endometrium or the inner one-third of myometrium. Other patients should have pelvic and para-aortic lymph nodes sampled at the time of hysterectomy. Therapeutic lymphadenectomy is not advocated; sampling of the external and internal iliac and obturator areas, as well as of the common iliac and para-aortic lymph nodes, is sufficient for patients with endometrial cancer. Those with a high likelihood of spread to pelvic lymph nodes (grade 3, the outer

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one-third myometrial or uterine serosal involvement, and those with high-risk histologic subtypes) should undergo sampling of the common iliac and para-aortic lymph nodes, because these areas lie outside the usual fields of pelvic radiotherapy. Patients with papillary serous tumors may present with metastases in the abdominal cavity or omentum much as those with ovarian epithelial tumors; omentectomy, diaphragmatic, and peritoneal biopsies should be obtained. Another important element of staging endometrial cancer is the evaluation of peritoneal lavage fluid for the presence of malignant cells. Approximately 12% of patients are found to have malignant peritoneal cytology; one-half have other evidence of extrauterine spread of the disease, but the remainder have no other associated risk factors. Malignant peritoneal cytology increases the risk for intra-abdominal failure and treatment for this finding deserves consideration. If external beam radiotherapy is not used, intraperitoneal radioactive chromic phosphate may be of benefit. Vaginal hysterectomy is occasionally useful in patients with early endometrial cancer when lymph node metastases are thought to be unlikely. This operation is particularly well suited for massively obese parous patients in whom an abdominal incision would be prohibitively difficult. It is unnecessary to perform radical surgery in women with endometrial cancer even if there is spread to the cervix (stage II). Although lymphatic spread is important, these cancers also may be disseminated by hematogenous or peritoneal routes. Radical surgery has never been shown to improve survival in comparison with simple hysterectomy and adjuvant radiotherapy. Simple, extrafascial, or complete abdominal hysterectomy is demonstrated in (Fig. 40-20) and contrasted with radical hysterectomy. It is critical to remove the ovaries in women undergoing surgery for endometrial cancer because 5% harbor occult metastases. Additionally, the source of estrogen secretion in premenopausal women with endometrial cancer should be removed. In patients with large stage IIB and III lesions, consideration is generally given to preoperative pelvic radiotherapy, because surgery may be otherwise difficult or impossible. These tumors should receive appropriate surgical staging or thorough radiographic evaluation if primary radiotherapy is used.

FIG. 40-20. Extent of simple (extrafascial) hysterectomy (left) as compared with radical hysterectomy (right).

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Pelvic exenteration is rarely necessary in the treatment of patients with endometrial cancer unless it occurs following full irradiation for a preexisting cervical cancer. However, such cases are rare. Radiotherapy alone may be the treatment of choice in patients at excessive risk for operative intervention. Radiotherapy alone produces results inferior to those of surgery or surgery and adjuvant radiotherapy, however; therefore patients treated without hysterectomy should be selected carefully. Advanced or recurrent endometrial cancer is responsive to progestin or tamoxifen therapy in 30% of unselected patients. Lesions that are well differentiated contain higher levels of progesterone receptor and respond more frequently. Only 10% of poorly differentiated cancers respond to hormonal treatment. Local radiotherapy or chemotherapy with paclitaxel, doxorubicin, platinum compounds, or combinations may be of benefit in some cases as well.

canal; (3) the superficial femoral lymph nodes, grouped around the saphenous vein just superficial to the fossa ovalis, with efferents to the deep femoral lymph nodes; (4) the deep femoral lymph nodes, including the most cephalad lymph node of Cloquet or Rosenm¨uller; and (5) the external iliac lymph nodes. Because the lymph node of Cloquet receives efferents from the inguinal region and the vulva and drains into the medial portion of the external iliac chain, it is an important sentinel in the route of spread of vulvar lesions to the pelvic lymph nodes. There are also direct lymphatic connections between the clitoris and Cloquet’s node. The 1988 FIGO staging system for vulvar cancer (Table 40-5) is currently accepted. This system requires surgical evaluation of the inguinal lymph nodes and provides a schema in which prognosis and therapy are closely linked with stage.

Vulvar Cancer

Treatment

Vulvar cancer accounts for approximately 5% of all gynecologic cancers. Although uncommon histologic types such as malignant melanoma and adenocarcinoma of the Bartholin’s gland occur, more than 90% of vulvar malignancies are squamous carcinomas. Epidemiologic risk factors include older age, smoking, previous intraepithelial or invasive squamous cancer of the cervix or vagina, chronic vulvar dystrophy (often associated with diabetes mellitus), and immunocompromise (organ-transplant recipients, systemic lupus erythematosus). Human papillomavirus-like DNA has been identified in both preinvasive and invasive squamous carcinomas of the vulva. Although the etiology of this cancer is not well understood, it is likely that the human papillomavirus plays an important role, especially in younger women. Spread of squamous carcinoma of the vulva is primarily via the lymphatics of the vulva. Lesions arising in the anterior aspect of the vulva drain preferentially to the inguinal lymph nodes, and posterior lesions may drain directly to the lymph nodes of the pelvis. Stanley Way of Great Britain identified five main groups of lymphatic drainage of carcinoma of the vulva (Fig. 40-21): (1) the superficial inguinal lymph nodes, which lie in the subcutaneous tissue overlying the inguinal ligament; (2) the deep inguinal lymph nodes, which lie along the course of the round ligament in the inguinal

Historically, the single-stage en bloc “extended” radical vulvectomy championed in Great Britain by Way, and in the United States by Friedrich Taussig, was used to treat all vulvar neoplasms (Fig. 40-22). In this operation, wide margins of skin and subcutaneous tissue around the primary tumor are removed together with underlying lymphatic structures in the groins and the labia majora and minora and clitoris in the vulva. Also removed are the proximal saphenous vein and its tributaries, the superficial circumflex iliac, superficial external pudendal, and superficial inferior epigastric veins. The deep inguinal lymph nodes are removed by opening the external oblique fascia overlying the inguinal canal; most of the round ligament is removed at the same time. Pelvic lymphadenectomy is easily performed by opening the transversalis fascia below the inguinal ligament and exposing the Table 40-5 FIGO Staging of Vulvar Cancer Stage 0 Tis Stage I T1 N0 M0 Stage IA Stage IB Stage II T2 N0 M0

Inguinal ligament Superficial inguinal lymph nodes Superficial circumflex iliac v.

Superficial inferior epigastric v. External inguinal ring Round ligament Superficial external pudendal v.

Fossa ovalis

Great saphenous v.

Superficial femoral lymph nodes

FIG. 40-21. Lymphatic drainage of the vulva delineated by Stanley Way.

Stage III T3 N0 M0 T3 N1 M0 T1 N1 M0 T2 N1 M0 Stage IV A T1 N2 M0 T2 N2 M0 T3 N2 M0 T4 Any N M0 Stage IV B Any T, Any N, M1

Carcinoma in situ, intraepithelial carcinoma. Tumor confined to the vulva and/or perineum—2 cm or less in greatest dimension. No nodal metastasis. ≤1 mm invasion + other criteria >1 mm invasion + other criteria Tumor confined to the vulva and/or perineum—more than 2 cm in greatest dimension. No nodal metastasis. Tumor of any size with 1) adjacent spread to the lower urethra and/or the vagina, or the anus, and/or 2) unilateral regional lymph node metastasis. Tumor invades any of the following: Upper urethra, bladder mucosa, rectal mucosa, pelvic bone, and/or bilateral regional node metastasis.

Any distant metastasis, including pelvic lymph nodes.

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FIG. 40-22. En bloc radical vulvectomy outlined by Way and Taussig.

external iliac vessels in the retroperitoneal space medial to the psoas muscle. Pelvic lymphadenectomy is probably not indicated in vulvar cancer except in those patients found to have grossly enlarged pelvic lymph nodes on preoperative CT or MRI. Patients with inguinal node metastases are best treated with inguinal and pelvic radiotherapy following resection of the inguinal lymph nodes. In the case of large vulvar primaries or suspicious inguinal lymph nodes, this approach yields better survival rates than those obtained when pelvic lymphadenectomy alone is performed. Because extended radical vulvectomy is associated with long hospital stays and significant morbidity from wound breakdown and infectious complications, there has been a long-standing interest in more conservative surgery for early vulvar cancer. The first efforts to this end were made in the 1960s. Several investigators introduced the concept of radical vulvectomy and inguinal lymphadenectomy through separate incisions. This approach not only reduces hospital time but also results in fewer major wound complications. This approach, illustrated in Fig. 40-23, has been widely embraced by gynecologic oncologists. Because inguinal node metastases are the result of an embolic process rather than infiltration or direct extension, the approach is rational. Early concerns regarding recurrence in the skin bridge between the vulvar and groin incisions have been largely allayed by experience with this approach. Recurrence in the skin bridge is usually associated with preexisting large inguinal metastases. Another area of progress in the surgical management of vulvar carcinoma has been the use of conservative surgery for early lesions of the vulva. Although specific criteria vary, most investigators recognize that squamous cancers of the vulva less than 2 cm in diameter and no more than 1 mm thick, and that are of histologic grade 1 or 2, are associated with a very small risk of inguinal metastases. Such lesions are adequately treated with deep, wide excision, provided skin margins of 1 cm are obtained and the dissection is carried to the level of the superficial transverse perineal muscles. Inguinal lymphadenectomy can be omitted in such patients.

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FIG. 40-23. Radical vulvectomy and inguinal lymphadenectomy through separate incisions.

In patients with intermediate lesions located on the labium minus or majus that do not cross the midline or involve midline structures such as the clitoris, perineal body, or perianal area, modified hemivulvectomy and ipsilateral inguinal lymphadenectomy have been used successfully. This approach should be considered if the primary lesion is less than 2 cm in diameter and 5 mm or less in thickness. Lymph node metastases are uncommon in this group of patients and the groin nodes may be evaluated by frozen section at the time of surgery. Sentinal lymph node biopsy is being evaluated in vulvar cancer. While it was once believed that superficial inguinal lymph nodes (Fig. 40-24) were “sentinel,” it has been demonstrated that vulvar cancer often involves the deep femoral lymph nodes primarily as well. A conservative groin incision (Fig. 40-25) can also be used to sample these lymph nodes. If “sentinel” lymph nodes are free of tumor, the risk of involvement of other groin or pelvic lymph nodes is probably small. Figure 40-26 depicts the outlines of the modified

Superficial femoral nodes Deep femoral nodes Cribriform fascia Femoral a. Camper's fascia Femoral n. Femoral v. Sartorius m. Pectineus m. Iliopsoas m. Adductor Femur Longus Epidermus Medial

FIG. 40-24. Superficial inguinal lymphadenectomy.

Lateral

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Femoral v. Pubic tubercle

based on the gracilis, sartorius, or tensor fasciae latae muscles. Approximately 50% of patients are cured by such surgical procedures. In recent years, such locally advanced lesions of the vulva also have been treated successfully with external beam radiotherapy combined with radiosensitizing drugs such as cisplatin. At the completion of combination therapy, the areas of involvement are excised widely or biopsied. This approach is associated with results as good as or better than those achieved with ultraradical surgery and generally results in less morbidity. The need for urinary and fecal diversion is also obviated.

Uncommon Vulvar Tumors Sapheno-femoral junction

FIG. 40-25. Incision recommended for superficial inguinal lymphadenectomy.

radical hemivulvectomy. This excision site may be closed primarily with good results. Another controversial area in the management of squamous carcinomas of the vulva is that of the patient with locally advanced disease. When extensive vulvar cancer involves more than the distal urethra, the vagina or rectovaginal septum, or the anal musculature, ultraradical surgery may be required. Anterior, posterior, or total pelvic exenteration may be necessary to resect such lesions successfully. The presence of fixed, matted, or ulcerating inguinal lymph nodes presents another problem that may require extensive surgical excision. Following such extirpative procedures, reconstruction of the vulva and groins is accomplished using myocutaneous flaps

Melanoma. Traditional surgical therapy for malignant melanoma of the vulva has included en bloc radical vulvectomy and inguinofemoral lymphadenectomy. It is now known that lesions less than 1 mm thick or Clark level II lesions may be treated conservatively with wide local excision. The value of inguinofemoral lymphadenectomy is controversial in lesions of greater depth, although primary surgical cure is occasionally achieved in patients with microscopic nodal metastases. Melanomas of the urethra or vagina are usually diagnosed in advanced stages and may require pelvic exenteration for successful management. Intraepithelial Disease. Intraepithelial disease (Bowen’s disease, bowenoid papulosis, vulvar intraepithelial neoplasia, carcinoma in situ) may be treated successfully by removing the involved epithelium. Characteristically, this is a raised, velvety lesion with sharply demarcated borders that may contain gray, brown, or red pigmentation. Removal is accomplished by simple vulvectomy, where the plane of dissection is limited to the epithelium, or by wide excision. In the case of diffuse intraepithelial disease, a so-called skinning vulvectomy and split-thickness skin graft may be required. This approach is associated with prolonged hospital stays, however, and should be reserved for exceptional cases. Also effective in the treatment of intraepithelial disease are the carbon dioxide laser and the electrosurgical loop. Paget’s disease is an unusual epithelial or invasive process characterized by the presence of distinct “Paget cells” in the involved epithelium. Grossly, the lesion is confluent, raised, red, and waxy in appearance. This lesion also can be excised widely, although the microscopic extent of the disease may exceed the visible margins. Intravenous fluorescein dye and ultraviolet light highlight areas that cannot be detected by the naked eye, and this assists in excision. Frozen-section examination of the surgical margins also is helpful but time-consuming. Paget’s disease is occasionally associated with an underlying invasive adenocarcinoma; careful pelvic examination and proctoscopy are indicated in patients with this process. Bartholin’s gland carcinoma represents less than 1% of all vulvar malignancies and may be squamous carcinoma, adenocarcinoma, or adenosquamous or adenoid cystic carcinoma. Hemivulvectomy with dissection of the ischiorectal fossa and resection of involved contiguous structures is indicated. Because of the risk of inguinofemoral metastases, groin lymphadenectomy should accompany the vulvar operation. GYNECOLOGIC OPERATIONS Dilatation and Curettage

FIG. 40-26. Extent of modified radical hemivulvectomy for stages I and II squamous cancer of the vulva.

At one time dilatation of the cervix and curettage of the endometrial cavity was among the most common surgical procedures performed in this country. Simple office biopsy and medical means of dealing

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with abnormal bleeding have largely replaced the need for diagnostic dilatation and curettage. In some cases curettage is necessary for the relief of profuse uterine hemorrhage. It is indicated for removal of endometrial polyp or therapeutic termination of pregnancy and for retained placental tissue following abortion or obstetric delivery. The patient is placed on the operating table in a lithotomy position, and the vagina and cervix are prepared as for any vaginal operation. The cervix is grasped on the anterior lip with a tenaculum. The cervix is gently pulled toward the outlet of the vagina. Some traction on the cervix is necessary to reduce the angulation between the cervical canal and the uterine cavity. A sound is inserted into the uterine cavity, and the depth of the uterus is noted. The cervical canal is then systematically dilated beginning with a small cervical dilator. Most operations can be performed after the cervix is dilated to accommodate a number 8 or 9 Hegar dilator or its equivalent. Dilatation is accomplished by firm, constant pressure with a dilator directed in the axis of the uterus (Fig. 40-27). After the cervix is dilated to admit the curette, the endocervical canal should be curetted and the sample submitted separate from the endometrial curettings. The endometrial cavity is then systemically scraped with a uterine curette. The curettings are collected on a small piece of gauze or Telfa. The curettings are then placed in the fixative. After the uterus has been thoroughly curetted, a ureteral stone forceps may be used to explore the endometrial cavity, searching for polyps or pedunculated neoplasms. When the procedure is

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complete, the tenaculum is removed; the tenaculum site is evaluated for bleeding, and, if the puncture sites are bleeding, they are treated with a small amount of silver nitrate. The major complication of dilatation and curettage is perforation of the uterus. Perforation is diagnosed when the operator finds no resistance to a dilator or curette at a point where the operator normally would expect it. Perforation generally is treated in an expectant manner. The patient should be watched for several hours for signs of hemorrhage and be warned of the possibility of pelvic infection. A falling hematocrit and other signs of intraperitoneal bleeding indicate the need for laparotomy and control of the bleeding site. Any infection following dilatation and curettage should be treated with antibiotics. Uterine curettage is often required for incomplete abortion in the first or second trimester of pregnancy. Dilatation of the cervix in these cases is invariably present. Curettage of the postabortal uterus must be approached carefully because the uterus is extremely soft and perforation can occur with very little warning. Using the largest curette available is a safer choice than a small curette, which tends to cause perforation with less pressure. In the postabortal uterus, the endometrial cavity must be scraped thoroughly until the distinctive gritty feeling of curette against muscle is felt. In recent years, suction curettage for incomplete abortion, hydatid mole, and therapeutic abortion has become popular. Suction machines fitted with cannulas that vary from 4 to 12 mm in diameter evacuate the uterus in less time and save blood loss. Most of these

FIG. 40-27. Dilatation and curettage of the uterus. A . Technique for uterine curettage; B . Common duct stone searcher; C . Introduction of Randall stone forceps into the endometrial cavity.

COMMON DUCT STONE SEARCHER

B A

C

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procedures are accomplished under sedation and paracervical block. Following the curettage, the uterine cavity is explored with a placental forceps or sponge forceps to remove any loose tissue within the cavity. Uterine perforation continues to be a concern when curettage is carried out for incomplete abortion. Perforation of the puerperal uterus is a much more serious problem because the organ is much more vascular than the nonpregnant uterus. Postoperative bleeding should be modest if the curettage has been complete. Some operators control bleeding with the use of uterotonic agents such as vasopressin and prostaglandin-17α.

Endoscopic Surgery Endoscopic surgery, including both laparoscopy and hysteroscopy, has assumed a major role in gynecology. Laparoscopy, once used almost exclusively for diagnostic purposes and for tubal ligation, is now being applied to almost every kind of gynecologic procedure. Hysteroscopy has found an expanded role from purely diagnostic to removal of intrauterine pathology and ablation of the endometrium for abnormal uterine bleeding. Although the limits of what is possible continue to be defined, the relative safety of some of these techniques in general use remains uncertain.

Laparoscopy Laparoscopy was developed more than 25 years ago as a diagnostic tool and was soon adapted to perform tubal sterilization techniques. From the beginning, a few intrepid gynecologists used this approach for much more, including lysis of pelvic adhesions, treatment of endometriosis, and removal of ectopic tubal pregnancies. Slowly the role of the laparoscope expanded for conservative surgery and for removal of diseased tissue. More recently, laparoscopic approaches were developed for hysterectomy and gynecologic oncologic procedures. Ongoing research and experience continue to

establish which of these approaches represent real advantages to the patients.

General Techniques for Laparoscopy Placement of the Veress Needle and Primary Trocar. The standard method for gynecologic laparoscopy remains the serial placement through the umbilicus of a retractable-pointed Veress needle for insufflation, followed by a sharp 5- or 10-mm primary trocar and sleeve. For decades, reusable instruments were standard. Today, disposable instruments are more commonly used despite continued concerns regarding both cost and safety. When placing the Veress needle through the anterior abdominal wall, the goal is to minimize the risk of preperitoneal placement while avoiding retroperitoneal vessel injury by the use of proper placement techniques. In patients who are of normal weight or who are overweight but not obese (i.e., less than 200 lb), instruments are placed through the umbilicus toward the pelvis. After the sacral prominence is palpated, the abdominal wall is elevated by grasping the skin and subcutaneous tissue midway between the symphysis pubis and the umbilicus in an effort to maximize the distance between the umbilicus and major vessels. The Veress needle is inserted through the base of the umbilicus at 45 degrees from horizontal. In the obese patient (>200 lb), the thickness of the abdominal wall requires an alteration of the approach for inserting the Veress needle. If the needle is placed through the base of the umbilicus at 45 degrees, it may not reach the peritoneal cavity (Fig. 40-28). For this reason, it has been suggested that the Veress needle be placed at near 90 degrees from horizontal. To minimize the risk of vascular injury, the umbilicus should be elevated (i.e., supported to avoid depression), and a standard length Veress needle should be used and checked for location as described previously. Following insufflation, a primary 5- or 10-mm trocar is also inserted at near 90 degrees from horizontal.

FIG. 40-28. Changes in the anterior abdominal wall anatomy with weight.

Umbilicus

Rectus Abdominis

Aorta Spine

13 ± 4cm 6±3cm

Non-Obese

10± 2cm

Overweight

Obese

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Alternatively, open laparoscopic techniques continue to be refined and more widely applied. For these techniques, the anterior rectus fascia is incised with a scalpel, the peritoneal cavity is entered bluntly, and a blunt-tipped trocar is placed into the peritoneal cavity. Pneumoperitoneum is maintained at the site of entry either by sutures or by mechanisms built into the sleeves such as balloons or fascial threads. Although once reserved for patients with previous surgery, many laparoscopists use an open technique exclusively to avoid the risk of major retroperitoneal injury and to minimize the risk of bowl injury associated with closed techniques. Placement of Secondary Trocars. As laparoscopic techniques advanced, the need for secondary trocars increased dramatically. After transillumination to locate the superficial vessels, an attempt is made to laparoscopically locate the inferior epigastric vessels. Secondary trocars are placed under laparoscopic visualization either 3 to 4 cm above the symphysis pubis in the midline, or 8 cm above the symphysis pubis approximately 8 cm lateral to the midline. This location approximates McBurney’s point on the right side of the abdomen. At the end of the procedure, the sleeves are removed and the sites observed for signs of hemorrhage. Any trocar site larger than 5 mm should be closed with a full-thickness suture (to include both the anterior and posterior rectus abdominus fascia) to prevent herniation through the defect. Power Instruments. Scissors and sutures have long been used for laparoscopic dissections and vessel ligation. However, because of the limitations of laparoscopy, including decreased depth perception and limited field of vision, innovative instruments have been developed for laparoscopic use both for tissue cutting and for vessel occlusion. Initially, unipolar electrosurgery was the only power instrument available, but because of concern about inadvertent damage to adjacent organs, other techniques were developed. Bipolar electrosurgery is excellent for hemostasis but has limited cutting ability. Laser, which can be aimed or placed in the proper location before activation, offers precision and some degree of hemostasis. Recently, an ultrasonic scalpel was developed that avoids both the smoke and char associated with other power techniques. Although the safety of these different instruments appears to be reasonably comparable, the difference in cost is dramatic and remains a significant concern. Methods for Large-Vessel Occlusion. As techniques to remove tissue with significant blood supplies (e.g., adnexa, uterus) were developed, methods to effectively divide and occlude major vessels also were developed. Laparoscopic suture ligation, using either intra- or extracorporeal knot tying, is relatively slow and technically difficult. For this reason, four alternative approaches are now widely applied. Pretied loops, linear stapling devices, bipolar electrocautery, and ultrasonic coagulating shears are all reasonably expeditious and effective, although cases of delayed bleeding have been reported. Once again, differences in cost remain an important consideration.

Laparoscopic Procedures Diagnostic Laparoscopy. This common procedure involves the placement of a 5- or 10-mm lens through an intraumbilical port, often with a 5-mm port placed above the symphysis for manipulation. Pelvic organs are closely inspected in a systematic fashion for signs of disease, and if tubal patency is an issue, a dilute dye solution is injected transcervically (chromopertubation). Biopsies can be obtained if malignancy is suspected. Tubal Sterilization Procedures. As in diagnostic laparoscopy, a one- or two-port technique can be used. Tubes are occluded in the mid-isthmic section (approximately 3 cm from the cornua) using

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clips, elastic bands, or bipolar electrosurgery. With electrosurgery, approximately 2 cm of tube should be desiccated. Pregnancy rates after any of these techniques have been reported in the range of 3 per 1000 women. Lysis of Adhesions. Pelvic adhesions usually are related to previous surgery, endometriosis, or infection, the latter of which can be either genital (i.e., pelvic inflammatory disease) or extragenital (e.g., ruptured appendix) in origin. Adhesions can be associated with decreased fertility or pain and can be lysed mechanically with scissors or any of the power techniques discussed above. Some degree of adhesion re-formation is unavoidable, and residual intrinsic tubal damage continues to interfere with fertility in most patients. Adhesion re-formation can be minimized by achieving good hemostasis using discrete application of electrosurgery. Postoperatively, intraperitoneal solutions are used commonly to “hydrofloat” the adnexal structures, but controlled studies of their efficacy have been disappointing. Barrier methods have been shown to decrease adhesion formation in both animal and human studies but have not been demonstrated to improve outcome in terms of either subsequent pregnancies or pain relief. Fulguration of Endometriosis. Conservative laparoscopic treatment of endometriosis increases fertility and often helps with pelvic pain. This condition and the various approaches to treatment were considered earlier in this chapter (see “Endometriosis”). Treatment of Ectopic Pregnancy. Laparoscopy has established itself as the primary treatment approach for ectopic pregnancies, a condition considered earlier in this chapter (see “Ectopic Pregnancy, Treatment”). Ovarian Cystectomy. The laparoscopic removal of ovarian cysts less than 6 cm in diameter in premenopausal women has become common. Using a multiple-port technique, the peritoneal cavity is inspected for signs of malignancy, including ascites, peritoneal or diaphragmatic implants, and liver involvement. In the absence of signs of malignancy, pelvic washings are obtained, and the ovarian capsule is excised with scissors or a power instrument. The cyst is shelled out carefully and placed in a bag, intact if possible. The bag opening is brought through the lower port incision along with the 10-mm port. The cyst is then drained and the cyst wall removed. Hemostasis of the ovary is achieved with bipolar electrosurgery, but the ovary is usually not closed, because this may increase postoperative adhesion formation. Except in the obvious cases of simple cysts, endometriomas, or dermoid cysts, the cyst wall should be sent for frozen section to verify the absence of the malignancy. If malignancy is detected, immediate definitive surgery, usually by laparotomy, is recommended. All cyst walls are sent for permanent section and pathologic diagnosis. In many cases the cyst will rupture prior to removal. This is always the case with an endometrioma that contains “chocolate” fluid. On rupture, the cyst contents are thoroughly aspirated, and the cyst wall is removed and sent for pathologic evaluation. The peritoneal cavity is copiously rinsed with Ringer’s lactate solution. This is especially important when a dermoid cyst is ruptured, because the sebaceous material can cause a chemical peritonitis unless all the visible oily substance is carefully removed. Although malignancies are not commonly encountered using these guidelines, there is concern that rupture may worsen the patient’s prognosis. Data are accumulating that suggest that cyst rupture may not alter prognosis. At the same time, laparoscopies in patients with ovarian malignancies are associated with an apparent high risk of port-sight metastases. Based on conventional wisdom, every effort should be made to remove ovarian cysts without

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intraperitoneal spillage. When a malignancy is diagnosed, definitive surgical treatment should not be delayed. Ovarian cysts larger than 6 cm and those discovered in postmenopausal women also can be removed laparoscopically. Because of the increased risk of malignancy associated with these situations, laparotomy is more commonly used. Laparoscopy may be a reasonable alternative in select patients if standard methods for staging are used in conjunction with appropriate frozen-section evaluation and expedient definitive therapy when indicated. Removal of Adnexa. Occasionally, all or part of an adnexa must be removed. This may be the case with a large tubal pregnancy, a large hydrosalpinx, or when a small but growing cyst is found in a postmenopausal woman. Using a multiple-port technique, the vascular supply to the tissue is first desiccated with bipolar cautery and then divided with scissors. Alternatively, the ovarian vessels in the infundibulopelvic ligament can first be occluded with one of the techniques described earlier (see “Methods for Large-Vessel Occlusion”). Special care should be taken to identify and avoid the ureter, which lies retroperitoneally as it crosses the ovarian vessels and courses along the ovarian fossa (see Fig. 40-3). Once the adnexa has been excised and hemostasis is achieved, attention is turned to removing the tissue from the peritoneal cavity. Small specimens can be removed using a retrieval bag via a 12-mm port. The port is removed with the sack, and the fascial incision is enlarged, if required. For larger specimens, the opening of the sack is exposed outside the abdomen while the specimen remains in the abdomen. A cyst can be aspirated, and the remaining specimen can be removed piecemeal, taking care not to allow intraperitoneal spillage. In difficult cases, the specimen can be removed via a colpotomy incision. For this procedure, a 12-mm port is placed through the posterior cul-de-sac under direct visualization. A retrieval sack is placed through the port, and the port and specimen in the sack are removed together. The distensible peritoneum and vaginal wall will allow the removal of a large specimen through a relatively small defect, which can then be closed with a running suture vaginally. Prophylactic antibiotics may decrease the risk of infection. Myomectomy. Uterine leiomyomas are often approachable via the laparoscope. Hemostasis is assisted by intrauterine injection of dilute vasopressin (10 U in 50 mL) at the site of incision. Pedunculated leiomyomas can be excised at the base using scissors or a power instrument. Intramural leiomyomas require deep dissection into the uterine tissue, which must be closed subsequently with laparoscopic suturing techniques. Because myomectomies are associated with considerable postoperative adhesion formation, barrier techniques are used to decrease adhesion formation. Removing the specimen can be difficult. In general, morcellation is required, and power morcellators have been developed that significantly expedite this technique. Although leiomyomas of any size or location technically can be removed laparoscopically, it is yet to be proven that either menorrhagia or infertility, the two most common indications for myomectomy, are as effectively treated laparoscopically as they are by laparotomy. Hysterectomy. Laparoscopy was first used to restore normal anatomy prior to vaginal hysterectomy. More recently, laparoscopy has been used to perform some or all of the actual hysterectomy to avoid laparotomy in patients with known pelvic adhesions, endometriosis, or in whom the uterus is enlarged by leiomyoma. Although multiple variations in technique exist, there are three basic laparoscopic approaches for hysterectomy: laparoscopicassisted vaginal hysterectomy (LAVH), laparoscopic hysterectomy (LH), and laparoscopic supracervical hysterectomy (LSH). While

basic techniques for each of these methods have become somewhat standardized, the indications and relative risk for each remain controversial. The technically simplest, and probably the most widely applied, is the LAVH. For this procedure, a multiple-port approach is used to survey the peritoneal cavity, and any pelvic adhesions are lysed. The round ligaments are then occluded and divided, and the uterovesical peritoneum is incised. Next, the proximal uterine blood supply is occluded and divided. When the ovaries are removed, the infundibulopelvic ligaments (containing the ovarian vessels) are divided. If the ovaries are conserved, the utero-ovarian ligament and blood vessels are divided and occluded. In some cases, the posterior culde-sac is also incised laparoscopically. The remainder of the case is performed vaginally, including dissection of the bladder from the anterior uterus, ligation of the uterine vessels, removal of the specimen, and closure of the vaginal cuff. A LH differs from an LAVH in that almost the entire hysterectomy is performed laparoscopically. This procedure is used for the indications listed above and also when lack of uterine descent makes the vaginal approach impossible. LH is begun in a manner identical to LAVH. But after the proximal uterine blood supply is divided, the bladder is dissected from the anterior uterus. This is followed by a retroperitoneal dissection in which the ureter is identified along its entire pelvic course and the uterine vessels are selectively occluded and divided. The ureterosacral ligaments are likewise divided and the posterior culde-sac incised. The specimen is removed vaginally, and the vaginal cuff is closed. The drawback to this approach is the reported increased risk of bladder and ureter injuries as compared to both abdominal and vaginal approach for hysterectomy. The third common laparoscopic approach is the LSH. This procedure has been advocated for all benign indications for hysterectomy. Technically, it is begun in a manner identical to the first two approaches. However, after the proximal vessels are divided and the bladder is dissected from the anterior uterus, the ascending branches of the uterine arteries are occluded and the entire uterine fundus is removed from the cervix. The endocervix is either cauterized or cored out with a special instrument. The fundus is then morcellated and removed through a 12-mm abdominal port or through a special transcervical morcellator. The end result is an intact cervix and cuff, with no surgical dissection performed near the uterine artery and adjacent ureter. This approach avoids both a large abdominal incision and a vaginal incision. According to its advocates, this approach minimizes operating time, recovery time, and risk of both infection and ureteral injury. LSH has yet to be widely applied, in part out of concern for the subsequent risk of developing cancer in the residual cervical stump. Oncologic Procedures. As techniques developed, it became apparent that laparoscopy also could be applied to oncologic procedures. In addition to the treatment of potentially malignant ovarian cysts, the laparoscopic approach also has been used for “second-look” and staging procedures, including peritoneal washes and biopsy, partial omentectomy, and pelvis and periaortic lymphadenectomy. If positive nodes are discovered, treatment options often do not include laparotomy, and thus major surgery can be avoided without compromising patient prognosis. Laparoscopic approaches have been developed for definitive procedures, notably laparoscopically-assisted radical vaginal hysterectomy. A guiding principle is that the same care must be rendered laparoscopically that would be performed by laparotomy with the same or less risk of complications. Until the relative risk of complications and effect on prognoses have been established for these approaches

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compared with laparotomy, application of the laparoscopic approach in gynecologic oncology will remain highly controversial.

Risks of Laparoscopy. The many unique aspects of laparoscopy contribute to the distinctive complications associated with this approach. Gas Embolism. Because pressurized CO2 is used routinely to insufflate the abdomen for laparoscopy, gas embolization continues to be a rare but serious complication. This is related most commonly to misplacement of the Veress needle used for insufflation prior to primary trocar insertion. If the tip of the needle inadvertently enters the aorta or its branches, temporary distal arterial occlusion will result. Because CO2 is quickly absorbed, no serious sequelae have been reported as a result of arterial embolization, but arterial bleeding from this injury can be serious. In contrast, inadvertent insufflation of the inferior vena cava or any of its venous branches can be fatal. Massive CO2 embolism can result in partial or complete pulmonary arterial obstruction. This serious complication can be avoided in most cases by careful determination of Veress needle location prior to insufflation. Techniques for this include (1) ensuring lateral mobility of the needle because retroperitoneal penetration will prevent this; (2) aspirating through the needle with a syringe to detect intravascular placement; and (3) use of the “hanging drop test,” in which a drop of saline placed on the hub of the needle is pulled into the hub of the needle when the abdominal wall is elevated to verify intraperitoneal placement. If any of these tests is not reassuring, the needle should be removed and replaced into the peritoneal cavity. When CO2 embolism is encountered, swift recognition and treatment can be lifesaving. Removal of the needle and placement of the patient in left lateral decubitus position are the first steps. In the presence of extreme hypotension, external cardiac massage has been suggested to break up large bubbles. Definitive treatment of this condition is central line placement and aspiration of the gas from the right-sided heart chambers and pulmonary vasculature. Injury to Abdominal Wall Vessels. Abdominal wall vessel injuries have become more common with the development of more complicated operative laparoscopic procedures that use lateral trocar placement and larger trocars. These vessels include the inferior (“deep”) epigastric vessels, the superficial epigastric vessels, and the superficial circumflex iliac vessels (Fig. 40-29). Injury to the inferior epigastric artery can result in life-threatening hemorrhage. Injury to these or other vessels can result in significant hematoma or postoperative blood loss if unrecognized. The primary methods to avoid vessel injury are knowledge of the vessels at risk and visualization of them prior to trocar placement when possible. The superficial vessels often can be seen and avoided by transillumination of the abdominal wall with the laparoscope. This is especially true in light-skinned and thin women. In contrast, the larger inferior epigastric vessels cannot be seen by transillumination because of their deeper location. But these vessels often can be seen laparoscopically and avoided as they course along the peritoneum between the lateral umbilical fold of the bladder and the insertion of the round ligament into the inguinal canal. Because the vessels may not be visible in some patients either by transillumination or laparoscopically, it is important to know their most likely location and place lateral trocars accordingly. Although the traditional location used for lateral trocar placement was approximately 5 cm from the midline, a safer location may be 8 cm or more above the symphysis pubis and 8 cm from the midline, because both the superficial and inferior epigastric arteries are located approximately 5.5 cm from the midline (see Fig. 40-29).

Deep Vessels

Inferior epigastric Deep circumflex iliac

Superficial Vessels

Superficial epigastric Superficial circumflex iliac

FIG. 40-29. Location of anterior abdominal wall blood vessels.

Anatomic variation and anastomoses between vessels make it impossible to know the exact location of all the abdominal wall vessels. For this reason, other strategies also should be used to avoid vessel injury, including the use of trocars with conical tips rather than pyramid tips, and the use of the smallest trocars possible lateral to the midline. Injury to Retroperitoneal Major Vessels. Injury to major retroperitoneal vessels is one of the least common but most serious complications of the closed laparoscopic technique, occurring in approximately 3 per 10,000 laparoscopies. This includes both vessel perforation by the Veress needle with intravascular insufflation and vessel laceration by the 5- or 10-mm primary trocar. Theoretically, the blind placement of sharp instruments through the umbilicus aimed toward the pelvis should rarely, if ever, result in vessel injury because both the aorta and the inferior vena cava bifurcate near level of the umbilicus. Unfortunately, in many patients the aortic bifurcation is at or below the level of the umbilicus, and in most patients the left common iliac vein crosses the midline below the umbilicus. The margin of error may be small, especially in thin patients, where the anteroposterior distance from the umbilicus to the retroperitoneal vessels may be as little as 2 to 3 cm (see Fig. 40-28). The primary strategy to minimize the risk of vessel injury is to vary the angle of insertion based on the weight of the patient (see “Placement of the Veress Needle and Primary Trocar”). An alternative strategy to avoid the risk is the exclusive use of an open technique. Although techniques for open laparoscopy have been available for years, the majority of gynecologic laparoscopic procedures are performed using a closed rather than an open technique. Because of the potential advantage of laparoscopy in terms of patient recovery time, complications, and cost, new techniques and instruments continue to be developed and evaluated. Intestinal Injury. Another potentially serious complication of laparoscopic surgery is injury to either small or large intestines. An unrecognized bowel injury may occur at the time of trocar insertion, especially if the patient has had previous abdominal procedures that often result in bowel adhesions to the anterior abdominal wall peritoneum. To minimize the risk of bowel injury in patients who have undergone previous laparotomy, many gynecologic surgeons recommend the use of an open technique.

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Other factors that appear to alter the risk of bowel injury include establishment of pneumoperitoneum prior to trocar placement and the type of primary trocar used. Placing the primary trocar without establishing a pneumoperitoneum appears to increase the risk of bowel injury threefold. The extreme sharpness of disposable trocars makes insertion through the anterior abdominal wall easier, but also has the potential to increase the risk of bowel injury. In one series, the risk of bowel injury with disposable trocars was approximately three times that previously reported for reusable trocars. Although the majority of disposable trocars have automatically extending shields designed to decrease the risk of inadvertent injury to these structures, no study has examined the relative safety of disposable versus reusable trocars. Another laparoscopic risk to bowel is thermal injuries that may occur when power sources are used, such as electrocautery or laser. Regardless of the cause, major bowel injuries usually become obvious during surgery. However, because of the limited field of view, some bowel injuries may not be seen during surgery. These injuries usually manifest 1 to 3 days after surgery, well after the patient has been released following these primarily outpatient procedures. Urologic Injuries. Bladder injury is an uncommon laparoscopic injury, most commonly occurring as a result of retroperitoneal perforation during lower trocar placement or during sharp dissection of the bladder from the lower uterine segment during hysterectomy. The latter of these two situations is usually recognized intraoperatively; the first sign of the former may be postoperative hematuria or lower-port incisional drainage. Once diagnosed, large defects require layered closure, whereas smaller defects usually close spontaneously within days or weeks with the aid of transurethral catheter drainage. Ureteral injury may occur as a result of any procedure that requires dissection or ligation of sidewall vessels, such as removal of an adnexa, because the ureter is adjacent to the pelvic peritoneum in the area of the ovarian fossa (see Fig. 40-3). This complication also has been reported after fulguration of endometriosis on the pelvic sidewall. Another common cause of ureteral injury is hysterectomy, because the ureter is often located less than 2 cm from the cervix. This type of injury appears to be increased during laparoscopic hysterectomy when compared to abdominal or vaginal hysterectomy, apparently because of the modification of the standard techniques required for the laparoscopic approach. Ureteral injuries, including complete ligation, partial resection, or thermal injuries, usually will manifest within hours to days of surgery. Complete obstruction most often manifests as flank pain, whereas the first sign of transection may be symptoms of intra-abdominal irritation caused by urine leakage. Transperitoneal thermal injuries resulting from fulguration of endometriosis may be similar to those after transection, but the appearance of symptoms may be delayed several days until tissue necrosis occurs. Incisional Herniation. Incisional hernias after laparoscopy were rare prior to the use of large secondary ports (>5 mm) lateral to the midline. In recent times, incisional hernias have become a well-appreciated problem. A small peritoneal defect below the rectus abdominis muscle can allow bowel to become entrapped beneath the anterior rectus abdominis fascia. For this reason, closure of both the anterior and posterior layers of the rectus abdominus fascia is recommended whenever trocars greater than 5 mm are used. Special needles have been developed for this purpose.

Hysteroscopy Hysteroscopy, like laparoscopy, has gained widespread support as a very useful technique for both diagnosis and treatment of intrauterine pathology and for ablation of the endometrium as an alternative to hysterectomy for the treatment of abnormal uterine bleeding.

General Hysteroscopic Techniques Type of Instruments. Hysteroscopes can be divided into the categories of diagnostic, operative, and hysteroresectoscope. The lens for all three is identical. This is usually a fiberoptic lens and light source with an outside diameter of 3 mm and an objective lens that is offset up to 30 degrees from the long axis of the instrument. In contrast, the sleeves for the three types of hysteroscopes vary considerably. The diagnostic sleeve usually has an external diameter of 5 mm and a single-direction flow. Because outflow is limited, bleeding may impede a clear intrauterine view. The operative sleeve, with an external diameter usually less than 10 mm, has a flow-through design with separate channels for input and outflow of distention media. A separate channel is available for placement of fine operating instruments. The final type of sleeve is the hysteroresectoscope. This is also of a flow-through design and has an integral unipolar resecting loop identical to a urologic resectoscope. The loop can be replaced with a roller bar for endometrial ablation. Distention Media and Pumps. Several distention media have found widespread use for hysteroscopy. For diagnostic hysteroscopy, CO2 gives excellent clarity. Although it is extremely safe in general use, fatal gas embolisms have been reported when CO2 was used after cervical dilatation or intrauterine surgery. To minimize this risk, CO2 should be used for diagnostic hysteroscopy only with specifically designed pumps that are relatively high pressure (80 to 90 mm Hg) and low flow. More importantly, the use of CO2 should be avoided after cervical dilatation or any uterine instrumentation. For operative hysteroscopy, one of the first fluid media used was 32% dextran and 70% dextrose. This syrup-like substance is usually introduced by hand with a large syringe. The advantage is simplicity and low cost. The view is excellent in the absence of bleeding. The disadvantage is the difficulty in completely removing the substance from the instruments. If this solution is allowed to dry in critical movable points, the instrument may “freeze up,” and it is very difficult to remove. In addition, intravascular intravasation can result in pulmonary edema. More recently, aqueous solutions with pressure-controlled pumps have been used. For operative hysteroscopy, where electrosurgery is not being used, it is safest to use a balanced salt solution, such as Ringer’s lactate. Moderate fluid intravasation will be of no consequence in a healthy individual. However, intravasation of larger volumes can result in fluid overload, especially in a patient with any cardiac compromise. To minimize this risk, the use of a fluid-medium pump is recommended rather than gravity or a pressure cuff. This allows the maximal pressure to be limited to approximately 80 mm Hg to prevent excess intravasation of distention media. When electrosurgery is used for hysteroresectoscope excision of leiomyomas or roller-blade endometrial ablation, a nonconducting solution such as glycine must be used. Significant vascular intravasation can cause hyponatremia, potentially resulting in cerebral edema, coma, or even death. For this reason, protocols must be followed rigorously to detect and treat significant intravasation

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whenever these solutions are used. Intraoperatively, differences in distention medium input and output should be calculated every 15 minutes. If the difference is greater than 500 mL, a diuretic should be given. If the difference is greater than 1000 mL, the procedure also should be terminated. Whenever significant intravasation is suspected, serum sodium level should be checked immediately postoperatively and a few hours later because later hyponatremia, presumably due to transperitoneal absorption, has been reported.

Hysteroscopic Procedures Diagnostic Hysteroscopy. This common procedure is often performed prior to uterine curettage to identify any focal abnormalities such as an endometrial polyp or a malignancy. This procedure is usually performed in the operating room with either general or regional anesthesia, although it has been performed by some as an office procedure with minimal analgesia. After determining the position of the uterus, the anterior cervix is grasped with a tenaculum and traction placed to straighten the cervical canal. The lens and diagnostic sleeve are placed into the cervix, and distention medium is introduced with a pressure of 80 to 90 mm Hg. The hysteroscope is advanced slowly and carefully toward the fundus, using tactile and visual cues to avoid perforation. The entire uterine cavity is inspected, and any abnormal anatomy is documented. As the hysteroscope is withdrawn, the uterocervical junction and the endocervix are examined. Directed Endometrial Biopsy. If a focal abnormality of the endometrium is observed, directed biopsy may be more accurate than a simple uterine curettage. The cervix is dilated to allow passage of an 8- to 10-mm flow-through operating hysteroscope, and a balanced salt solution is used for distention. Once the hysteroscope is positioned in the uterine cavity, the area of interest is biopsied under direct visualization. Polypectomy. If an intrauterine polyp is discovered, the base of the polyp is incised with hysteroscopic scissors, and the polyp is grasped with grasping forceps. The hysteroscope, sleeve, and polyp are removed simultaneously, because most polyps will not fit through the operating channel. Extremely large polyps may have to be removed piecemeal. Any residual base of the polyp may be removed with biopsy forceps. Uterine Septum Resection. A septum may be resected with scissors, electrosurgery, or laser. Scissors are used most commonly in light of the minimal vascularity of septa and the decreased potential for bowel injury should inadvertent uterine perforation occur. An operating hysteroscope is placed into the uterine cavity, which will appear to be two tubular structures rather than the broad uterine fundus usually encountered. The septum is then evenly divided across the fundus. If scissors are used, rather than a power cutting instrument, the presence of bleeding indicates that the level of resection is shifting from the avascular septum to the vascular myometrium. After surgery, no special device is placed in the uterus because intrauterine synechiae formation is uncommon. Removal of Intrauterine Synechiae. Intrauterine synechiae are almost always associated with previous uterine curettage, especially when performed in the immediate postpartum period. These synechiae may result in amenorrhea or infertility. The removal of synechiae is performed in a manner similar to that described above for a uterine septum, with some differences. The first is that the anatomy, and thus the visual cues for location of normal uterine wall, are completely unpredictable from patient to

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patient. Preoperative hysterosalpingography is usually very helpful. Findings can vary from a few small synechiae to complete obliteration of the cavity. In difficult cases, simultaneous transabdominal ultrasound is extremely helpful in guiding the direction and limits of hysteroscopic resection. Standby laparoscopy should be available in the event of perforation, which is a significant risk in these patients. However, once pneumoperitoneum is achieved, abdominal ultrasound is no longer possible. Following surgery, some type of intrauterine splint, such as an intrauterine device or a balloon catheter, is often placed to avoid synechia re-formation. Patients are usually placed on estrogen supplementation for a month and prophylactic antibiotics until the intrauterine splint is removed 1 to 2 weeks later. Intrauterine Myomectomy. Pedunculated or submucosal leiomyoma can be removed safely hysteroscopically with subsequent improvement in both abnormal uterine bleeding and infertility. Because myoma tissue is relatively dense, a power cutting instrument is required. The choices are either laser or, more commonly, electrosurgery. For argon or Nd:YAG laser, a fiber is placed through the operating channel of the operating hysteroscope, and a balanced salt solution is used for distention. When electrosurgery is used via a hysteroresectoscope, an electrolyte-free solution, such as glycine or sorbitol, must be used because a balanced salt solution will dissipate the current and prevent cutting. Use of an electrolyte-free solution requires a thorough understanding of the potential risk and prevention of hyponatremia, because fatal complications have been reported with its use (see “Fluid Overload and Hyponatremia” below). Both pedunculated and submucosal fibroids are shaved into small pieces with either the laser fiber or the hysteroresectoscope. In the case of a pedunculated fibroid, the urge to simply transect the stalk as a first step should be resisted unless the fibroid is 10 mm or less in size. Fibroids that are larger than this are difficult to remove in one piece without excessive cervical dilatation. Morcellation is much easier when the stalk is still attached for stability. When the field of view is obscured by multiple pieces of tissue, the hysteroresectoscope is removed and the tissue collected in the urologic pouch. The hysteroscope is replaced in the uterus, and the procedure is repeated until the pedunculated fibroid and its stalk are completely removed, or the submucosal fibroid is shaved flush to the adjacent wall of the uterine cavity. After surgery, some gynecologists will treat the patient with estrogen or place an intrauterine splint as described above (see “Removal of Intrauterine Synechiae” above). Endometrial Ablation. A common treatment for abnormal uterine bleeding in the absence of endometrial hyperplasia is ablation of the endometrium. In the recent past, this was performed with an operative hysteroscope using a laser fiber or with a resectoscope using an electrosurgical “roller barrel.” As described previously for myoma resection, a balanced salt solution is used for laser resection, and an electrolyte-free solution is used for electrosurgery. For both techniques, the endometrium is destroyed down to the myometrium in a systematic fashion starting at the cornua and ending in the lower uterine segment. Electrosurgery has been used for resection of the endometrium with a loop electrode as well as for ablation. Both loop resection and laser ablation may have a somewhat greater chance of subsequent amenorrhea, but both appear to be technically more difficult with a greater risk of perforation than the more widely applied roller-barrel electrosurgical ablation.

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More recently, hysteroscopic endometrial ablation has been widely supplanted by balloon thermal ablation. For this procedure, a probe with attached balloon is blindly placed into the uterus. Heated saline is circulated in the balloon to coagulate the endometrium. Balloon ablation requires less technical skill and appears to have less risk of complication than the hysteroscopic approaches. Both hysteroscopic and balloon ablation techniques result in amenorrhea in approximately half the patients and decreased menstruation in another third of the patients over the first year of therapy. However, a large portion of these patients subsequently will require another ablative procedure for bleeding or a hysterectomy for residual bleeding or dysmenorrhea. A theoretical risk of endometrial ablation is the delay of vaginal bleeding if the patient subsequently develops an endometrial malignancy. However, after more than a decade of widespread application of these techniques, this has not manifested as a significant risk. Nevertheless, the long-term risk of this problem remains uncertain and patients undergoing this procedure should be aware of this.

A. SUBUMBILICAL B. MIDLINE C. RECTUS OR PARAMEDIAN D. PFANNENSTEIL / JOEL – COHEN E. "J" INCISION H F. CHERNEY OR MAYLARD G G. INGUINAL H. McBURNEY

A B

C

D E F

Risks of Hysteroscopy Gas Embolism. Gas embolism has been reported when using CO2 for distention after intrauterine surgery. It is recommended that CO2 not be used for any operative procedure or after significant dilation of the cervix. If symptoms of massive gas embolism occur during diagnostic hysteroscopy, the procedure should be stopped and the patient treated as described above (see “Risks of Laparoscopy, Gas Embolism” above). Fluid Overload and Hyponatremia. During operative hysteroscopy, significant intravasation of distention medium can occur through venous channels opened during surgery or transperitoneally as a result of any fluid forced through the tubes. Symptomatic fluid overload has been reported with all fluid distention media, including 32% dextran 70 in dextrose. The volume of distention medium introduced through the operating hysteroscope or hysteroresectoscope should always be compared with the volume retrieved using a urologic collection drape. When using a balanced salt solution (e.g., Ringer’s lactate), symptomatic fluid overload is treated effectively with diuretics. When electrolyte-free solutions are used for electrosurgery, the potential exists for serious and even fatal hyponatremia, even without significant fluid overload. Electrolyte-free solutions should not be used for hysteroscopy when electrosurgery is not required. When these solutions are used, careful monitoring of fluid balance should be performed every 15 minutes to detect intravasation. Uterine Perforation and Bowel Injury. Uterine perforation is a common risk of uterine dilation prior to hysteroscopy. If it is not possible to distend the uterine cavity when the hysteroscope is placed in the uterus, perforation should be suspected. If no sharp instrument or power source has been placed through the defect, expectant outpatient management is appropriate. Occasionally, perforation will occur during resection of a septum or leiomyoma or other operative procedures. If any chance of bowel injury exists, laparoscopy to evaluate contiguous bowel for injury is a reasonable precaution. Intrauterine Synechia. The formation of adhesions between the anterior and posterior uterine walls, referred to as synechiae, is an uncommon complication after intrauterine surgery. Although intrauterine devices, intrauterine catheters, and highdose estrogen therapy have been advocated to decrease the risk of this complication, the efficacy of these treatments remains uncertain.

FIG. 40-30. Incisions useful for pelvic surgery.

Abdominal Procedures Incisions The pelvic surgeon must consider a number of factors before beginning a pelvic operation. The most important requirement is that the incision provides adequate exposure for the anticipated procedure. Pelvic surgery is performed through vertical and transverse incisions. Figure 40-30 shows the majority of the incisions used in pelvic surgery. The midline incision is the most useful. It is simple and tends to bleed less than incisions made off the midline. The midline incision provides excellent exposure of the pelvis, and, when necessary, the entire abdomen is accessible for operation. This incision is more susceptible to hernia formation and is somewhat more uncomfortable than the transverse incision. The resulting scar occasionally is thicker than incisions made along Langer’s lines, resulting in a less-desirable cosmetic result. Transverse incisions are used more often by a pelvic surgeon because the entire incision is centered over the area of operative interest. The incisions are more comfortable postoperatively and heal with a lower incidence of dehiscence or hernia formation. The most common transverse incision is the Pfannenstiehl incision (Fig. 40-31). The skin is incised transversely approximately 2 cm above the symphysis pubis, and the incision is taken down to the rectus fascia, which is entered transversely. The rectus fascia is dissected bluntly away from the underlying rectus muscles in both a superior and inferior direction. The rectus muscles are separated in the midline, and the peritoneum is opened in the vertical midline. The Maylard incision carries with it the advantages of a transverse incision but affords more exposure of the pelvis than that provided by the Pfannenstiehl. The skin is incised transversely approximately 2 cm above the symphysis pubis, and the rectus fascia is opened transversely but not separated from the underlying rectus muscles. The rectus muscles are cut directly under the fascial incision, and several small bleeders in the body of the rectus muscles are clamped and coagulated. The epigastric artery and vein located just

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Rectus m.

Transversalis fascia and peritoneum

Incision

A

Pyramidalis m.

B Deep epigastric vessels

Peritoneum

C

D

FIG. 40-31. Pfannenstiehl incision (see text for description).

below the lateral edge of the rectus muscles are ligated and cut; the peritoneum is then opened transversely to afford good visualization and access to the entire pelvis. The Cherney incision provides the advantages of a transverse incision and all the visibility provided by the Maylard incision. The incision is made in the transverse direction in the lower abdomen approximately 2 cm above the symphysis, the rectus fascia is opened transversely, the lower portion of the rectus sheath is dissected free of the rectus muscle, and the insertion of the rectus muscles on the symphysis pubis is visualized. The tendon of the rectus muscle is then cut free of the symphysis pubis, and the muscle is allowed to retract upward. The peritoneum is opened transversely. This incision is repaired by simply sewing the rectus tendon to the lower aspect of the rectus sheath just above the symphysis before closing the rectus sheath at the completion of the operation. All the incisions used in pelvic surgery have advantages as well as disadvantages. The pelvic surgeon should anticipate the need for surgical exposure in the upper abdomen and in such cases choose a vertical incision. The Pfannenstiehl incision is suitable for most operations for benign disease in the pelvis, but if wide pelvic or upper abdominal exposure is needed, the Maylard or Cherney incisions provide better operative exposure.

Hysterectomy for Benign Disease The abdomen is entered through an appropriate incision. The upper abdomen is examined for evidence of extrapelvic disease, and a suitable retractor is placed in the abdominal wound. The selfretaining bowel is packed out of the pelvis and held in place with a retractor. The uterus is grasped at either cornu with Kocher clamps and pulled up into the wound (Fig. 40-32A). The round ligament is identified and suture ligated and cut (Fig. 40-32B). If the ovaries are to be removed, the peritoneal incision is extended from the round ligament lateral to the infundibulopelvic ligament for approximately 2.5 cm. The retroperitoneal space is bluntly opened. The ureter is identified on the medial leaf of the broad ligament. The infundibulopelvic ligament is isolated, clamped, and cut, and the suture ligated. A similar procedure is carried out on the opposite side. In the event that the ovaries are not to be removed, after ligating the round ligament, an avascular area in the broad ligament is chosen and the broad ligament bluntly fractured with a finger, producing an opening below the ovarian ligament and fallopian tube (see Fig. 40-32C). The fallopian tube and ovarian ligament are clamped, cut, and ligated.

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Round ligament

Bladder

Uterus

Round ligament Fallopian tube Ovary

A

B

Bladder

Ovarian ligament

Fallopian tube

C

D

Ureter

Ureter

Cardianal ligament

Ureterine vessels

E

F

FIG. 40-32. Hysterectomy. A . The uterus grasped at the cornua. B . The round ligament is cut. C . The ovarian ligament and fallopian tube are isolated. D . The bladder is mobilized. E . The uterine vessels are clamped. F . The cardinal ligaments are clamped. (Continued)

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Vagina Vagina

Cardinal ligament

G

H

Vagina

I

Upward traction is placed on the uterus. The peritoneum in the anterior cul-de-sac is opened between the ligated round ligaments. The bladder is mobilized by sharply dissecting it free of the anterior surface of the uterus and cervix (see Fig. 40-32D). The uterine vessels are skeletonized by transilluminating the fold of the broad ligament and dissecting the avascular tissue off the uterine vessels. The peritoneum on the posterior surface of the uterus is dissected free of the uterus and then cut. Clamps are placed on the uterine vessels at the cervicouterine junction. The vessels are cut and the clamps replaced with suture ligatures (see Fig. 40-32E). The bladder is again examined to ensure that it has been mobilized sufficiently from the vagina near the cervix. The cardinal ligaments are clamped, cut, and ligated (see Fig. 40-32F). Following division of the cardinal ligaments, the uterus is elevated and the vagina entered with scissors or a knife (see Fig. 40-32G). The uterus and cervix are cut free of the vagina. Sutures are placed at each lateral angle of the vagina, and the cardinal ligament is sutured to either lateral vaginal angle (see Fig. 40-32H). The central portion of the vagina is left open after repairing it with a running absorbable suture (see Fig. 40-32I). Pelvic reperitonealization is not necessary. The rectosigmoid colon is allowed to return to the pelvis. The pelvic packs are

FIG. 40-32. (continued) G . The vagina is entered. H . The cardinal ligaments are sutured to the vagina. I . The vagina is “closed open.”

removed and the small bowel is allowed to return to the pelvis. The omentum is placed over the bowel and under the abdominal wound. The abdominal wound is closed in an appropriate manner. In some circumstances, uterine myomata interfere with the operative procedure and myomectomy or supracervical hysterectomy might be accomplished before removing the cervix.

Myomectomy Myomectomy should be performed through an incision that will allow good visibility of the pelvis. Hemostasis for the procedure is aided by the placement of a Penrose drain (Fig. 40-33A) around the base of the uterus and pulled through small perforations in the broad ligament lateral to the uterine blood supply on either side. This “uterine tourniquet” is held in place with a clamp. Further hemostasis may be obtained by placing bulldog or rubber-shod clamps on the infundibulopelvic ligament in order to control the utero-ovarian blood supply. When possible, the uterine incision should be made in the anterior surface of the uterus in order to reduce the incidence of postoperative adhesions. An incision is made through the uterine musculature (see Fig. 40-33B) into the

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A

D

SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

B

C

E

F

FIG. 40-33. Myomectomy. A . Hemostatic “tourniquet’“ in place before myomectomy. B . Uterine incision for myomectomy. C . Removal of myoma. D . Several myomas may be removed through a single incision. E . The uterine wound is closed with absorbable suture. F . The uterine wound covered with mesh to retard adhesions.

myoma. The pseudocapsule surrounding the tumor is identified and the tumor is bluntly dissected out with scissors, a knife handle, or a finger. After the tumor is freed of its lateral attachments, it can be twisted to expose a pedicle that frequently contains its major blood supply (see Fig. 40-33C). On occasion, several myomas may be removed through a single incision (see Fig. 40-33D). The uterine wounds are closed with absorbable sutures to obliterate the dead space and provide hemostasis (see Fig. 40-33E). The uterine serosa is closed with a 000 absorbable suture placed subserosally if possible. A patch of Interceed to cover the uterine incision may prevent adhesion formation(Fig. 40-33F).

Radical Hysterectomy (Modified from Okabayashi) The patient is placed in a modified lithotomy position with legs in obstetric stirrups, hips abducted 45 degrees and flexed 15 degrees. The peritoneal cavity is entered through a Maylard incision (Fig. 40-34A) after ligating and dividing the inferior epigastric vessels (Fig. 40-34B). The Maylard incision permits unequaled exposure of structures on the lateral pelvic sidewall. Access to the retroperitoneum is obtained by dividing the round ligaments (Fig. 40-34C).

A U-shaped incision is carried from one lateral abdominal gutter to the other, including the peritoneum of the bladder reflection (Fig. 40-34D). The pararectal and paravesical spaces are opened using blunt digital or instrument dissection, and narrow rigid retractors are placed to maintain exposure (Fig. 40-34E). Pelvic lymphadenectomy is performed by removing lymph nodes from the external, internal, and common iliac vessels (Fig. 40-34F), as well as the obturator fossa (Fig. 40-34G). If there are no pelvic lymph node metastases, para-aortic lymph node sampling is unnecessary. Isolation of the superior vesicle artery by lateral retraction brings the uterine artery into view; this vessel is skeletonized and clipped at its origin from the anterior division of the internal iliac artery (Fig. 40-34H). The branches of the posterior division are generally not visualized at the time of radical hysterectomy. Next, the structures inferior to the uterine artery in the cardinal ligament are clamped and divided (Fig. 40-34I); freeing the cervix and upper vagina from the lateral pelvic sidewall. A linear stapling device may expedite this portion of the procedure. At this point, the proper ovarian ligaments and the proximal fallopian tubes may be transected between clamps (see Fig. 40-34J). After the ovarian vessels are mobilized, the ovaries may be marked

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Round ligament

Uterus

A

Fallopian tube

B

Ovary

C Vesicouterine fold Paravesical space

External iliac vessels

Internal iliac artery

Lymph nodes Uterine vessels

D

Pararectal space

E

F

FIG. 40-34. Radical hysterectomy. A . Exposure of the inferior epigastric vessels before transection of the rectus muscles. B . Ligation of the inferior epigastric vessels before transection of the rectus muscles. C . Ligation and division of the round ligaments opens the pelvic retroperitoneum. D . First peritoneal incision lateral to the ovarian vessels and across the vesicouterine fold. E . Narrow malleable retractors (Indiana retractors) are placed into the paravesical and pararectal spaces to provide excellent access to the lateral pelvic sidewall and pelvic lymph nodes. F . Pelvic lymphadenectomy (external and internal iliac vessels). (Continued)

with vascular clips and suspended in the lateral abdominal gutters above the pelvic brim. This measure protects the ovaries if postoperative pelvic radiotherapy is to be given. The ureters are carefully detached from the posterior leaves of the broad ligament for a short distance and retracted laterally (Fig. 40-34K) before the posterior cul-de-sac is entered and the rectovaginal space developed bluntly (see Fig. 40-34L); the uterosacral ligaments are divided. Upward traction on the uterus facilitates dissection of the bladder inferiorly away from the underlying cervix and upper vagina. The ureters are freed from their investment in the paracervical tissue, allowing the bladder and ureters to be displaced inferolaterally, exposing the upper vagina and paravaginal tissues. The tissues are clamped and cut, taking care to remove a 3- to 4-cm “cuff” of vagina with the cervix (see Fig. 40-34M). The vagina is closed, a suprapubic catheter is inserted, and the abdominal incision is repaired. Radical hysterectomy is associated with 85 to 90% cure rates in patients without lymph node, parametrial, or marginal involvement, and with 65 to 70% cure rates in those with spread to the regional nodes. The primary morbidity is bladder denervation, which occurs to some extent in almost all women undergoing this procedure. Generally, loss of bladder sensation is the only deficit, although inability to void is not uncommon in the immediate postoperative period. Rectal dysfunction may result in difficult defecation. Ureterovaginal fistulas occur in approximately 1% of all patients in recent studies. Postoperative external beam radiotherapy may be elected if nodal metastases, positive surgical margins, or parametrial tissue

involvement is found. Because bladder and ureteral complications are more common in women undergoing postoperative radiotherapy, surgical candidates must be chosen with care.

Resection of Ovarian Cancer Radical or modified radical hysterectomy is indicated in the treatment of epithelial ovarian cancer only if peritoneal tumor nodules obliterate the posterior cul-de-sac or extend to the retroperitoneal spaces. Generally, extrafascial (simple or conservative) hysterectomy (see Fig. 40-20) suffices in the resection of these tumors. When hysterectomy and salpingo-oophorectomy are completed, the infracolic omentum should be removed by reflecting the fatty organ superiorly, isolating and dividing the right and left gastroepiploic vessels, and dissecting through the avascular posterior leaf before isolating and dividing the vessels in the anterior leaf of the omentum. If the omentum contains a large amount of disease, the gastrocolic omentum should be removed by isolating and dividing the short gastric vessels along the greater curvature of the stomach. In cases of extensive omental involvement, care must be taken not to injure the spleen, stomach, or transverse colon. Generous peritoneal biopsies should be obtained from the right hemidiaphragm, both lateral abdominal gutters, and the anterior and posterior peritoneum of the pelvis. If gross intraperitoneal tumor is completely resected, the lymph nodes should be evaluated. The left para-aortic lymph nodes may be exposed by reflecting the sigmoid colon medially. These lymph

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

Superior vesical artery

G Uterine artery

I H

Fallopian tube

Uterosacral ligament

Ureter

J Ovary and ligament

K L

Vagina

Ureter

M FIG. 40-34. (continued) G. Pelvic lymphadenectomy (obturator fossa). H . Development of the uterine and superior vesical arteries. I . The uterine artery has been clipped and divided near its origin. J . The proper ovarian ligament and proximal fallopian tube is clamped and divided if the ovary is to be preserved. K . The ureters have been detached from the posterior peritoneum of the broad ligament and are retracted laterally. The rectovaginal space is developed using blunt finger dissection. L . Transection of the uterosacral ligaments. M . Clamps are placed on the lateral vagina, taking care to remove 3 to 4 cm of the upper vagina.

nodes should be liberally sampled, keeping in mind that the primary venous drainage of the left ovary is the left renal vein and that of the right ovary is the inferior vena cava at the level of the renal vein. Metastases are more common above than below the inferior mesenteric artery. The right para-aortic lymph nodes may be sampled transperitoneally or by mobilizing the ileocecal area and reflecting it superiorly.

Pelvic lymph node sampling is also an important aspect of surgical staging in ovarian cancer and is completed by removing lymph nodes from the distribution of the external and internal iliac vessels and obturator space above the level of the obturator nerve. This part of the staging procedure is facilitated by first opening the paravesical and pararectal spaces as described for radical hysterectomy above. Lymph node sampling is primarily a diagnostic procedure in the

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B A C

F D

G

E

H

I

FIG. 40-35. Vaginal hysterectomy. A . Traction is placed on the uterus. B . The posterior cul-de-sac is entered. C . The vaginal mucosa is circumcised. D . The anterior cul-de-sac is entered. E . The uterosacral ligaments are clamped. F . The uterosacral ligaments are tied. G. The fallopian tube, round ligament, and ovarian ligament are ligated. H . The peritoneum is closed. I . The vaginal mucosa is closed.

management of early ovarian cancers. There is little evidence that complete lymphadenectomy is therapeutic in patients with advanced and unresected disease.

Vaginal Procedures Hysterectomy The removal of the uterus through the vagina is preferred in many cases of myoma, uterine prolapse, intraepithelial neoplasia,

and uterine bleeding disorders. Patients are more comfortable and operative time, hospital stay, and recovery time are shorter than in cases of abdominal operation. Vaginal hysterectomy is an acceptable approach in those patients in whom the uterus descends, the bony pelvis allows vaginal operation, the uterine tumors are small enough to permit vaginal removal, and the patient is amenable to vaginal operation. In the presence of large myomas, pretreatment with a GnRHa will allow vaginal operation that would have been impossible previously.

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The patient is placed in a high lithotomy position, and the pelvis is examined under anesthesia. This examination should confirm previous findings and provide assurance that the operation is possible through the vaginal route. The bladder is not catheterized before operation unless it is greatly distended. A weighted vaginal speculum is placed in the posterior vagina, and the cervix is grasped with a tenaculum and pulled in the axis of the vagina (Fig. 40-35A). The posterior cul-de-sac is identified and entered with scissors (Fig. 40-35B). Mayo scissors are used to circumcise the cervix, and the mucosa is cut down to the pubocervical-vesical fascia (Fig. 40-35C). The vaginal mucosa and the bladder are sharply and bluntly dissected free of the cervix and the lower portion of the uterus. Care must be taken not to injure the bladder. When the peritoneum of the anterior cul-de-sac is identified, it is entered with the scissors, and a retractor is placed in the defect (see Fig. 40-35D). The uterosacral ligaments are identified, doubly clamped, cut, and doubly ligated (see Fig. 40-35E). The second ligature is held long. Serial clamps are placed on the parametrial structures above the uterosacral ligament; these pedicles are cut, and the clamps are replaced with ties (see Fig. 40-35F). At the cornu of the uterus, the tube, round ligament, and suspensory ligament of the ovary are doubly clamped and cut (see Fig. 40-35G). The procedure is carried out on the opposite side, and the uterus is removed. The first clamp is replaced with a free tie; the second clamp is replaced with a suture ligature that is transfixed. The second suture ligature is held long. The pelvis is inspected for hemostasis; all bleeding must be meticulously controlled at this point. The pelvic peritoneum is closed with a running purse-string suture incorporating those pedicles which were held (see Fig. 40-35H). This exteriorizes those areas which might tend to bleed. The sutures attached to the ovarian pedicles are cut. The vagina may be closed with interrupted mattress stitches, incorporating the uterosacral ligaments into the corner of the vagina with each lateral stitch (see Fig. 40-35I). The vaginal cuff is inspected again for hemostasis. In most cases, no vaginal packing is required. A catheter is left in the bladder until the patient has fully awakened and is ambulatory. On occasion, the uterus, which is initially too large to remove vaginally, may be reduced in size by morcellation (Fig. 40-36). After the uterine vessels have been clamped and ligated, serial wedges are taken from the central portion of the uterus in order to reduce the uterine mass. This procedure will allow the vaginal delivery of even very large uterine leiomyomas.

Pessaries The vaginal pessary has been used since ancient times. It involves placing a plastic or rubber device into the vagina to support the vaginal apex and the vaginal walls. The device is finding little use in modern gynecology. When pessaries are used, they should be removed at least every 4 weeks. They produce discomfort secondary to pelvic pressure, and vaginal ulceration secondary to pressure necrosis is common.

Injuries Associated with Pelvic Surgery Intestinal Injury. Adhesion formation is the most common antecedent to enterotomy at the time of pelvic operation. When lysis of adhesions is carefully carried out, this complication should occur rarely. Injuries to the small bowel range from serosal tears to through-and-through lacerations. Serosal tears are usually oversewn with a 4-0 nonabsorbable suture. Injuries to the lumen of the bowel are generally repaired using single- or double-layer closure; a single layer of 4-0 absorbable suture followed by an outer layer of

FIG. 40-36. Uterine morcellation through the vagina.

interrupted nonabsorbable suture is effective. Lacerations that are extensive or involve multiple areas should be treated by resecting the injured segment. Injury to the colon may occur during an operation to remove a left adnexal mass. When this injury occurs in a prepared colon, it is primarily repaired in a two-layer closure similar to that used in a small bowel repair. Large injuries may require resection of a segment of the colon. Injury to the unprepared large bowel is a significant problem. A small wound that is promptly recognized may be treated primarily with a single- or double-layer closure. The patient should be treated with intraoperative and postoperative antibiotics to cover both anaerobic and aerobic organisms. A major injury to unprepared large bowel will require colostomy in most cases.

Ureteral Injury. Ureteral injury at the time of pelvic surgery is uncommon and largely preventable. The ureters are at highest risk when the infundibulopelvic ligament is clamped for removal of an ovary and when the uterine arteries or cardinal ligaments are clamped during the course of hysterectomy. In most cases, visualization or palpation of the ureter before placing a hemostatic clamp will avoid this complication. The ureter is at highest risk in the course of pelvic operation for endometriosis, pelvic inflammatory disease, and pelvic neoplasia. The surgery for most of these conditions allows the dissection of the ureter beginning at the pelvic brim with meticulous exposure down to and through the operative field. Transection of the ureter high in the pelvis may allow primary reanastomosis of the ureter. Ureteral injuries near the bladder generally require ureteral reimplantation into the bladder. Bladder Injury. The pelvic surgeon must be constantly aware of the proximity of the bladder to the cervix and the anterior portion of the uterine fundus. The bladder must be dissected carefully free of the cervix at the time of hysterectomy. Hemostasis should be meticulous, and large clamps and ligatures should be avoided to prevent devitalization of the bladder wall. Operative entry into the bladder should be recognized immediately. If there is any question about the integrity of the bladder at the time of hysterectomy, a dilute solution of methylene blue will detect the defect and allow for closure.

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Bladder injuries must be fully visualized in preparation for repair irrespective of whether they were produced by vaginal or abdominal operation. The surgeon must ascertain that the wound does not involve the ureter and that the resulting repair will not compromise ureteral function. At either extent of the bladder laceration, 4-0 polyglycolic acid sutures are placed and held for retraction. The suture does not enter the lumen of the bladder. Once the bladder injury is delineated by the two initial sutures, the wound is closed with 4-0 interrupted polyglycolic acid suture in a running mattress stitch in order to strengthen the first layer and to remove any tension produced by the initial closure. An indwelling catheter should remain in the bladder for 5 to 7 days or until microscopic hematuria has disappeared. Some pelvic surgeons test their repair with a small amount of sterile milk. Milk is preferred to methylene blue or indigo carmine because it will not stain the tissue, allowing subsequent testing.

Bibliography Baggish MS, Sze EH: Endometrial ablation: A series of 568 patients treated over an 11-year period. Am J Obstet Gynecol 174:908, 1966. Copeland LJ: Textbook for Gynecology. St. Louis: CV Mosby, 1993. Herbst AL, Michell D, et al: Comprehensive Gynecology, 2d ed. St. Louis: CV Mosby, 1992.

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Hoskins WJ, Perez. CA, Young RC (eds): Gynecologic Oncology. Philadelphia: JB Lippincott, 1992. Hurd WW, Bude RO, et al: The location of abdominal wall blood vessels in relationship to abdominal landmarks apparent at laparoscopy. Am J Obstet Gynecol 171:642, 1994. Kurman RJ: Blaustein’s Pathology of the Female Genital Tract, 4th ed. New York: Springer-Verlag, 1994. Lee RH: Atlas of Gynecologic Surgery. Philadelphia: WB Saunders, 1992. Nichols DH: Gynecologic and Obstetric Surgery. St Louis: CV Mosby, 1993. Rubin SC, Sutton GP (eds): Ovarian Cancer, 2nd ed. New York: McGrawHill, 2002. Saidi MH, Sadler RK, et al: Diagnosis and management of serious urinary complications after major operative laparoscopy. Obstet Gynecol 87:272, 1996. Shingleton HM, Fowler WC, et al (eds): Gynecologic Oncology. Philadelphia: WB Saunders, 1996. Singer A, Monaghan JM: Lower Genital Tract Precancer. Boston: Blackwell Scientific, 1994. Speroff L, Glass RH, Kase NG: Clinical Gynecologic Endocrinology and Infertility, 5th ed. Baltimore: Williams and Wilkins, 1994. Steege JF: Laparoscopic approach to the adnexal mass. Clin Obstet Gynecol 37:392, 1994. Thompson JD, Rock JA (eds): TeLinde’s Operative Gynecology, 7th ed. Philadelphia: JB Lippincott, 1992.

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CHAPTER

41

Neurosurgery Michael L. Smith and M. Sean Grady

Neuroanatomy

Tumors of the Central Nervous System

Neurologic Examination

Intracranial Tumors Metastatic Tumors Glial Tumors Astrocytomas Oligodendroglioma Ependymoma Choroid Plexus Papilloma Neural Tumors and Mixed Tumors Medulloblastoma Ganglioglioma Neural Crest Tumors Miscellaneous Tumors Meningioma Vestibular Schwannoma (Acoustic Neuroma) Pituitary Adenoma Hemangioblastoma Lymphoma Embryologic Tumors Craniopharyngioma Epidermoid Dermoid Teratoma Spinal Tumors Extradural Tumors Intradural Extramedullary Tumors Intramedullary Tumors

Diagnostic Studies Plain Films Computed Tomography Magnetic Resonance Imaging Angiography Electromyography and Nerve Conduction Studies Invasive Monitoring Neurologic and Neurosurgical Emergencies Raised Intracranial Pressure Brain Stem Compression Stroke Seizure Trauma Head Trauma Glasgow Coma Scale (GCS) Score Scalp Injury Skull Fractures Closed Head Injury Traumatic Intracranial Hematomas Vascular Injury Brain Death Spine Trauma The Mechanics of Spine Trauma Patterns of Injury Initial Assessment and Management Neurologic Syndromes Studies Definitive Management Continued Care Peripheral Nerve Trauma Types of Injury Management of Peripheral Nerve Injury Patterns of Injury Cerebrovascular Disease Ischemic Diseases Thrombotic Disease Management Embolic Disease Common Types of Strokes Management Hemorrhagic Diseases Hypertension Amyloid Angiopathy Cerebral Aneurysm Arteriovenous Malformations

Spine Stability Neural Compression Myelopathy Radiculopathy Patterns of Disease Cervical Radiculopathy Cervical Spondylotic Myelopathy Thoracic Disc Herniation Lumbar Radiculopathy Neurogenic Claudication Cauda Equina Syndrome Spine Fusion Surgery Spinal Instrumentation Arthrodesis Peripheral Nerve Peripheral Nerve Tumors Schwannoma Neurofibroma Malignant Nerve Sheath Tumors Entrapment Neuropathies

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Ulnar Neuropathy Carpal Tunnel Syndrome Autoimmune and Inflammatory Disorders Guillain-Barr´e Syndrome Myasthenia Gravis Eaton-Lambert Syndrome Infection Cranial Osteomyelitis Subdural Empyema Brain Abscess Spine Pyogenic Vertebral Osteomyelitis Tuberculous Vertebral Osteomyelitis Discitis Epidural Abscess Functional Neurosurgery Epilepsy Surgery Anterior Temporal Lobectomy Corpus Callosotomy Hemispherectomy Deep Brain Stimulators Essential Tremor Parkinson’s Disease Trigeminal Neuralgia Stereotactic Radiosurgery Arteriovenous Malformations Vestibular Schwannomas Intracranial Metastases Congenital and Developmental Anomalies Dysraphism Spina Bifida Occulta Spina Bifida with Myelomeningocele Encephalocele Craniosynostosis Hydrocephalus Communicating Hydrocephalus Obstructive Hydrocephalus Chiari I Malformation

Neurologic surgery is a discipline of medicine and the specialty of surgery that provides the operative and nonoperative management (i.e., prevention, diagnosis, evaluation, treatment, critical care, and rehabilitation) of disorders of the central, peripheral, and autonomic nervous systems, including their supporting structures and vascular supply; the evaluation and treatment of pathologic processes that modify the function or activity of the nervous system, including the hypophysis; and the operative and nonoperative management of pain. As such, neurologic surgery encompasses the treatment of adult and pediatric patients with disorders of the nervous system. These disorders include those of the brain, meninges, skull and skull base, and their blood supply, including surgical and endovascular treatment of disorders of the intracranial and extracranial vasculature supplying the brain and spinal cord; disorders of the pituitary gland; disorders of the spinal cord, meninges, and vertebral column, including those that may require treatment by fusion, instrumentation, or endovascular techniques; and disorders of the cranial and spinal nerves throughout their distribution.

An accurate history is the first step toward neurologic diagnosis. A history of trauma or of neurologic symptoms is of obvious interest, but general constitutional symptoms also are important. Neurologic disease may have systemic effects, while diseases of other symptoms may affect neurologic function. The patient’s general medical ability to withstand the physiologic stress of anesthesia and surgery should be understood. A detailed history from the patient and/or family, along with a reliable physical examination will clarify these issues.

NEUROANATOMY An understanding of neuroanatomy is the foundation of comprehensive neurologic examination and diagnosis. Salient features will be considered, from cephalad to caudad. The cerebral hemispheres (or telencephalon) consist of the cerebral cortex, underlying white matter, the basal ganglia, hippocampus, and amygdala. The cerebral cortex is the most recently evolved part of the nervous system. Its functions are mapped to discrete anatomic areas. The frontal areas are involved in executive function, decision making, and restraint of emotions. The motor strip, or precentral gyrus, is the most posterior component of the frontal lobes, and is arranged along a homunculus with the head inferior and lateral to the lower extremities superiorly and medially. The motor speech area (Broca’s area) lies in the left posterior inferior frontal lobe in almost all right-handed people and in up to 90% of left-handed people. The parietal lobe lies between the central sulcus anteriorly and the occipital lobe posteriorly. The postcentral gyrus is the sensory strip, also arranged along a homunculus. The rest of the parietal lobe is involved with awareness of one’s body in space and relative to the immediate environment, body orientation, and spatial relationships. The occipital lobes are most posterior. The visual cortex is arrayed along the apposing medial surfaces of the occipital lobes. The left occipital lobe receives and integrates data from the left half of each retina. A left occipital lesion would therefore result in inability to see objects right of center. The temporal lobes lie below the sylvian fissures. The hippocampus, amygdala, and lower optic radiations (Meyer’s loops) are important components of the temporal lobe. They are involved in memory, emotion, and visual pathways, respectively. The receptive speech area (Wernicke’s area) lies in the area of the posterior superior temporal lobe and the inferior parietal lobe, usually on the left. The basal ganglia include the caudate, putamen, and the globus pallidus. Basal ganglia structures are involved with modulation of movement via inhibition of motor pathways. Lying deep to the cerebral hemispheres is the diencephalon, which includes the thalamus and hypothalamus. The thalamus is a key processor and relay circuit for most motor and sensory information going to or coming from the cortex. The hypothalamus, at the base of the brain, is a key regulator of homeostasis, via the autonomic and neuroendocrine systems. The brain stem consists of the midbrain (mesencephalon), pons (metencephalon), and medulla (myelencephalon). Longitudinal fibers run through the brain stem, carrying motor and sensory information between the cerebral hemispheres and the spinal cord. The corticospinal tract is the major motor tract, while the medial lemniscus and the spinothalamic tracts are the major sensory tracts. The nuclei of cranial nerves III through XII are also located within the brain stem. These nerves relay the motor, sensory, and special sense functions of the eye, face, mouth, and throat. The cerebellum arises from the dorsal aspect of the brain stem. It integrates somatosensory, vestibular, and motor information for coordination and timing of movement. Midline, or vermian, lesions lead to truncal

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ataxia. Lateral, or hemispheric, lesions lead to tremor and dyscoordination in the extremities. The ventricular system is a cerebrospinal fluid (CSF)-containing contiguous space inside the brain, continuous with the subarachnoid space outside the brain. The paired lateral ventricles consist of temporal, occipital, and frontal horns, as well as the main body. CSF travels from each lateral ventricle through the foramina of Monroe to the third ventricle, located between the left and right thalami. CSF then drains through the cerebral aqueduct to the fourth ventricle in the brain stem. The foramen of Magendie (midline) and paired foramina of Luschka (lateral) drain to the subarachnoid space. Choroid plexus creates the CSF, mostly in the lateral ventricles. The average adult has an approximate CSF volume of 150 mL and creates approximately 500 mL per day. The spinal cord starts at the bottom of the medulla and extends through the spinal canal down to approximately the first lumbar vertebra. Motor tracts (efferent pathways) continue from the brain stem down via the lateral and anterior corticospinal tracts to anterior horn cells, and then exit via ventral nerve roots. Sensory information (afferent pathways) enters via dorsal nerve roots, travels up the dorsal columns (proprioception and fine touch) or the spinothalamic tract (pain and temperature) and into the brain stem. Paired nerves exit the spinal cord at each level. There are 31 pairs: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. The dorsal and ventral nerve roots at each level fuse to form mixed motor-sensory spinal nerves and spread through the body to provide innervation to muscles and sensory organs. The C5–T1 spinal nerves intersect in the brachial plexus and divide to form the main nerve branches to the arm, including the median, ulnar, and radial nerves. The L2–S4 spinal nerves intersect in the lumbosacral plexus and divide to form the main nerve branches to the leg, including the common peroneal, tibial, and femoral nerves. The principal motor tract is the corticospinal tract. It is a twoneuron path, with an upper motor neuron and a lower motor neuron. The upper motor neuron cell body is in the motor strip of the cerebral cortex. The axon travels through the internal capsule to the brain stem, decussates at the brain stem–spinal cord junction, and travels down the contralateral corticospinal tract to the lower motor neuron in the anterior horn at the appropriate level. The lower motor neuron axon then travels via peripheral nerves to its target muscle. Damage to upper motor neurons results in hyperreflexia and mild atrophy. Damage to lower motor neurons results in flaccidity and significant atrophy. The two major sensory tracts are three-neuron paths. The fine touch and proprioception signals ascend ipsilaterally via the dorsal column, synapse and decussate in the lower medulla, travel up the contralateral medial lemniscus to the second synapse in the thalamus, and then ascend to the sensory cortex. The pain and temperature fibers synapse in the dorsal horn of the spinal cord at their entry level, decussate, and travel up the contralateral spinothalamic tracts to the thalamus. The second synapse occurs in the thalamus, and the output ascends to the sensory cortex. The nervous system is composed of the somatic nervous system and the autonomic nervous system (ANS). The motor and sensory tracts described so far compose the former. The latter carries messages for homeostasis and visceral regulation from the central nervous system (CNS) to target structures such as arteries, veins, the heart, sweat glands, and the digestive tract.1 CNS control of the ANS arises particularly from the hypothalamus and the nucleus of the tractus solitarius. The ANS is divided into the sympathetic, parasympathetic, and enteric systems. The sympathetic system drives the “fight or flight” response, and uses epinephrine to increase heart

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rate, blood pressure, blood glucose, and temperature, and to dilate the pupils. It arises from the thoracolumbar spinal segments. The parasympathetic system promotes the “rest and digest” state, and uses acetylcholine to maintain basal metabolic function under nonstressful circumstances. It arises from cranial nerves III, VII, IX, and X, and from the second to fourth sacral segments. The enteric nervous system controls the complex synchronization of the digestive tract, especially the pancreas, gallbladder, and small and large bowels. It can run autonomously, but is under the regulation of the sympathetic and parasympathetic systems.

NEUROLOGIC EXAMINATION The neurologic examination is divided into several components and is generally done from head to toe. First assess mental status. A patient may be awake, lethargic (will follow commands and answer questions, but then returns to sleep), stuporous (difficult to arouse at all), or comatose (no purposeful response to voice or pain). Cranial nerves may be thoroughly tested in the awake patient, but pupil reactivity, eye movement, facial symmetry, and gag are the most relevant when mental status is impaired. Motor testing is based on maximal effort of major muscle groups in those able to follow commands, while assessing for amplitude and symmetry of movement to deep central pain may be all that is possible for stuporous patients. Table 41-1 details scoring for motor assessment tests. Characteristic motor reactions to pain in patients with depressed mental status include withdrawal from stimulus, localization to stimulus, flexor (decorticate) posturing, extensor (decerebrate) posturing, or no reaction (in order of worsening pathology). Figure 41-1 diagrams the clinical patterns of posturing. This forms the basis of determining the Glasgow Coma Scale motor score, as detailed in Table 41-2. Light touch, proprioception, temperature, and pain testing may be useful in awake patients but is often impossible without good cooperation. It is critical to document sensory patterns in spinal cord injury patients. Muscle stretch reflexes should be checked. Often comparing left to right or upper extremity to lower extremity reflexes for symmetry is the most useful for localizing a lesion. Check for ankle-jerk clonus or up-going toes (the Babinski test). Presence of either is pathologic and signifies upper motor neuron disease.

Diagnostic Studies Plain Films Plain x-rays of the skull may demonstrate fractures, osteolytic or osteoblastic lesions, or pneumocephaly (air in the head). The use of skull plain films has decreased given the rapid availability and significantly increased detail of head computed tomography (CT) scans. Plain films of the cervical, thoracic, and lumbar spine are used to assess for evidence of bony trauma or soft-tissue swelling suggesting fracture. Spinal deformities and osteolytic or osteoblastic Table 41-1 Motor Scoring System Grade

Description

0 1 2 3 4 5

No muscle contraction Visible muscle contraction without movement across the joint Movement in the horizontal plane, unable to overcome gravity Movement against gravity Movement against some resistance Normal strength

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pathologic processes also will be apparent. The shoulder girdle usually poses problems in visualizing the cervicothoracic junction clearly.

Computed Tomography The noncontrast CT scan of the head is an extremely useful diagnostic tool in the setting of new focal neurologic deficit, decreased mental status, or trauma. It is rapid and almost universally available in hospitals in the United States. Its sensitivity allows for the detection of acute hemorrhage. A contrast-enhanced CT scan will help show neoplastic or infectious processes. In the current era, contrast CT is generally used for those patients who cannot undergo magnetic resonance imaging (MRI) scanning due to pacemakers or metal in the orbits. Fine-slice CT scanning of the spine is helpful for defining bony anatomy and pathology, and is usually done after an abnormality is seen on plain films, or because plain films are inadequate (especially to visualize C7 and T1 vertebrae). Finally, high-speed multislice scanners, combined with timed-bolus contrast injections, allow CT-angiography (CT-A). A thin-slice axial scan is obtained during the passage of contrast through the cerebral arteries and reconstructed in 3-D to assess for vascular lesions. CT-A does not reliably detect lesions, such as cerebral aneurysms, less than 3 mm across, but can provide detailed morphologic data of larger lesions. Newer, multislice scanner technology is approaching the resolution of conventional angiography.

Magnetic Resonance Imaging MRI provides excellent imaging of soft tissue structures in the head and spine. It is a complex and evolving science. Several of the most clinically useful MRI sequences are worth describing. T1 sequences made before and after gadolinium administration are useful for detecting neoplastic and infectious processes. T2 sequences facilitate assessment of neural compression in the spine by the presence or absence of bright T2 CSF signals around the cord or nerve roots. Diffusion-weighted images (DWI) can detect ischemic stroke earlier than CT. Fine-slice time-of-flight (TOF) axial images can be reformatted in three dimensions to build MRI-angiograms (MR-A) and MRI-venograms (MR-V). MR-A can detect stenosis of the cervical carotid arteries or intracranial aneurysms greater than 3 mm in diameter. MR-V can assess the sinuses for patency or thrombosis.

Angiography Transarterial catheter-based angiography remains the gold standard for evaluation of vascular pathology of the brain and spine. The current state of the art is biplanar imaging to reduce dye load and facilitate interventional procedures. Digital subtraction technologies minimize bony interference in the resultant images. Bilateral carotid arteries and bilateral vertebral arteries may be injected and followed through arterial, capillary, and venous phases for a complete cerebral angiogram.

Electromyography and Nerve Conduction Studies FIG. 41-1. Patterns of motor responses associated with various lesions. A . Left hemispheric lesion with right hemiplegia and left localization. B . Deep cerebral/thalamic lesion with bilateral flexor posturing. C . Midbrain or pontine lesion with bilateral extensor posturing. D . Medullary lesion with general flaccidity. [Adapted with permission from: Rengachary SS, Duke DA: Impaired consciousness, in Rengachary SS, Wilkins RA (eds): Principles of Neurosurgery. London: Wolfe Publishing Ltd., 1994, p 3.10.]

Electromyography and nerve conduction studies (EMG and NCS) are useful for assessing the function of peripheral nerves. EMG records muscle activity in response to a proximal stimulation of the motor nerve. NCS records the velocity and amplitude of the nerve action potential. EMG/NCS is typically performed approximately 4 weeks after an acute injury, as nerves distal to the injury continue to transmit electrical impulses normally until degeneration of the distal nerve progresses.

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Table 41-2 The Glasgow Coma Scale (GCS) Scorea Motor Response (M) Obeys commands Localizes to pain Withdraws from pain Flexor posturing Extensor posturing No movement

Verbal Response (V) 6 5 4 3 2 1

Oriented Confused Inappropriate words Unintelligible sounds No sounds

Eye-Opening Response (E) 5 4 3 2 1

Opens spontaneously Opens to speech Opens to pain No eye opening

4 3 2 1

a Add the three scores to obtain the Glasgow Coma Scale score, which can range from 3 to 15. Add “T” after the GCS if intubated and no verbal score is possible. For these patients, the GCS can range from 2T to 10T.

Invasive Monitoring There are several methods of monitoring intracranial physiology. The three described here are bedside intensive care unit (ICU) procedures and allow continuous monitoring. All three involve making a small hole in the skull with a hand-held drill. They are generally placed in the right frontal region to minimize the neurologic impact of possible complications, such as hemorrhage. The most reliable monitor, always, is an alert patient with a reliable neurologic exam. If a reliable neurologic exam is not possible due to the presence of brain injury, sedatives, or paralytics, and there is active and unstable intracranial pathology, then invasive monitoring is required.

External Ventricular Drain (EVD). An EVD is also known as a ventriculostomy. A perforated plastic catheter is inserted into the frontal horn of the lateral ventricle. An uninterrupted fluid column through a rigid tube allows transduction of intracranial pressure (ICP). CSF also can be drained to reduce ICP or sampled for laboratory studies.

or reactive edema. Blood volume can increase by extravasation to form a hematoma, or by reactive vasodilation in a hypoventilating, hypercarbic patient. CSF volume increases in the setting of hydrocephalus. Figure 41-2 demonstrates classic CT findings of hydrocephalus. Addition of a fourth element, such as a tumor or abscess, will also increase ICP. The pressure-volume curve depicted in Fig. 41-3 demonstrates a compensated region with a small P/V, and an uncompensated region with large P/V. In the compensated region, increased volume is offset by decreased volume of CSF and blood. Increased ICP can injure the brain in several ways. Focal mass lesions cause shift and herniation. Temporal lesions push the uncus medially and compress the midbrain. This is known as uncal herniation. The posterior cerebral artery passes between the uncus and

Intraparenchymal Fiberoptic Pressure Transducer. This device is commonly referred to as a “bolt.” Again, a small hole is drilled in the skull. A threaded post locks securely into the skull and holds the fiberoptic catheter in place. A bolt allows ICP monitoring only, but is smaller and less invasive than a ventriculostomy, and may be associated with fewer complications, although the data are not clear.

Brain Tissue Oxygen Sensors. The brain tissue oxygen sensor is a recent development. The device is screwed into the skull in the same manner as the bolt; however, the sensor catheter is an electrochemical oxygen–tension sensitive membrane. A single bolt can be designed to accept a pressure sensor, oxygen sensor, and brain temperature sensor. Patients with severe brain injury due to trauma or aneurysmal hemorrhage may benefit from placement of these three sensors and a ventriculostomy to drain CSF for control of ICP. This requires two twist-drill holes, which may be adjacent or on opposite sides of the head. NEUROLOGIC AND NEUROSURGICAL EMERGENCIES Raised Intracranial Pressure ICP normally varies between 4 and 14 mm Hg. Sustained ICP levels above 20 mm Hg can injure the brain. The Monro-Kellie doctrine states that the cranial vault is a rigid structure, and therefore the total volume of the contents determines ICP. The three normal contents of the cranial vault are brain, blood, and CSF. The brain’s contents can expand due to swelling from traumatic brain injury (TBI), stroke,

FIG. 41-2. Head CT scan demonstrating hydrocephalus. The third ventricle (3rd) is widened and rounded, the anterior horns of the lateral ventricles are plump, and pressure-driven flow of CSF into brain parenchyma adjacent to the ventricles is seen (arrowhead). This is known as transependymal flow of CSF.

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100 High Compliance

INTRACRANIAL PRESSURE (mm Hg)

90

Low Compliance

No Compliance

80 70 ∆P

60 50 40

∆V

30 ∆P

20 10

0

∆V

10

20

30

40

∆V

∆P

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60

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80

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INTRACRANIAL VOLUME ( ARBITRARY UNITS) FIG. 41-3. Pressure-volume curve demonstrating the effect of changing the volume of intracranial contents on ICP. Note the compensated zone, with little change of pressure with change of volume, and the uncompensated zone, with significant change of pressure with change of volume. [Adapted with permission from Rengachary SS, Duke DA: Increased intracranial pressure, cerebral edema, and brain herniation, in Rengachary SS, Wilkins RA (eds): Principles of Neurosurgery. London: Wolfe Publishing Ltd., 1994, p 2.3.]

midbrain and may be occluded, leading to occipital infarct. Masses higher up in the hemisphere can push the cingulate gyrus under the falx cerebri. This is known as subfalcine herniation. The anterior cerebral artery branches run along the medial surface of the cingulate gyrus and may be occluded, leading to medial frontal and parietal infarcts. Diffuse increases in pressure in the cerebral hemispheres can lead to central, or transtentorial, herniation. Increased pressure in the posterior fossa can lead to upward central herniation or downward tonsillar herniation through the foramen magnum. Uncal, transtentorial, and tonsillar herniation can cause direct damage to the very delicate brain stem. Figure 41-4 diagrams patterns of herniation. Patients with increased ICP, also called intracranial hypertension (ICH), will often present with headache, nausea, vomiting, and progressive mental status decline. Cushing’s triad is the classic presentation of ICH: hypertension, bradycardia, and irregular respirations. This triad is usually a late manifestation. Focal neurologic deficits may also be present if there is a focal mass lesion causing the problem. Patients with these symptoms should have a head CT as soon as possible. Initial management of ICH includes airway protection and adequate ventilation. A bolus of mannitol up to 1 g/kg causes free water diuresis, increased serum osmolality, and extraction of water from the brain. The effect is delayed by about 20 minutes and has a transient benefit. Driving serum osmolality above 300 mOsm/L is of indeterminate benefit and can have deleterious cardiovascular side effects, such as hypovolemia that leads to hypotension and decreased brain perfusion. Cases of ICH usually need rapid neurosurgical evaluation. Ventriculostomy or craniotomy may be needed for definitive decompression.

It is critical to note that lethargic or obtunded patients often have decreased respiratory drive. This causes the partial pressure of arterial carbon dioxide (Paco2 ) to increase, resulting in cerebral vasodilation and worsening of ICH. This cycle causes a characteristic “crashing patient,” who rapidly loses airway protection, becomes apneic, and herniates. Emergent intubation and ventilation to reduce Paco2 to roughly 35 mm Hg can reverse the process and save the patient’s life.

Brain Stem Compression Disease in the posterior fossa (brain stem and cerebellum) requires special consideration. The volume of the posterior fossa is small. Hemorrhage or stroke in the posterior fossa causes mass effect and can rapidly kill the patient in two ways. Occlusion of the fourth ventricle causes acute obstructive hydrocephalus, leading to raised ICP, herniation, and then death. The mass effect can also lead directly to brain stem compression (Fig. 41-5). Symptoms of brain stem compression include progressive obtundation and hypertension, followed rapidly by brain death. A patient with evidence of either or both needs emergent neurosurgical evaluation for possible ventriculostomy and suboccipital craniectomy (removal of the bone covering the cerebellum). This situation is especially critical, as expeditious decompression can lead to significant functional recovery of patients who present near brain death.

Stroke Patients who present with acute focal neurologic deficits for whom the time of onset of symptoms can be clearly defined (i.e., when the patient was last seen in a normal state of health) must be evaluated

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1

3 2

4

FIG. 41-4. Schematic drawing of brain herniation patterns. 1. Subfalcine herniation. The cingulate gyrus shifts across midline under the falx cerebri. 2. Uncal herniation. The uncus (medial temporal lobe gyrus) shifts medially and compresses the midbrain and cerebral peduncle. 3. Central transtentorial herniation. The diencephalon and midbrain shift caudally through the tentorial incisura. 4. Tonsillar herniation. The cerebellar tonsil shifts caudally through the foramen magnum. [Adapted with permission from Cohen DS, Quest DO: Increased intracranial pressure, brain herniation, and their control, in Rengachary SS, Wilkins RA (eds): Principles of Neurosurgery, 2nd ed. London: Wolfe Publishing Ltd., 1996, p 345.]

as rapidly as possible. An emergent head CT scan should be done. This is often normal, because CT changes from ischemic stroke may take up to 24 hours to appear (Fig. 41-6). A patient with a clinical diagnosis of acute stroke less than 3 hours old, without hemorrhage on CT, may be a candidate for thrombolytic therapy with tissue plasminogen activator (tPA).

Seizure A seizure is defined as uncontrolled neuronal electrical activity. New-onset seizure often signifies an irritative mass lesion in the brain. Tumors commonly present with seizure. Patients with traumatic intracranial hemorrhage are at risk for seizure. A seizing patient is at risk for neural damage if the seizure is not stopped, as well as airway and ventilation problems. Any patient with newonset seizure should have imaging of the brain, such as a head CT scan, after the seizure is controlled and the patient resuscitated.

TRAUMA Trauma is the leading cause of death in children and young adults; however, incidences of death and disability from trauma have been slowly decreasing. This is partly attributable to increased awareness of the importance of using seat belts and bicycle and motorcycle helmets. However, trauma remains a major cause of morbidity and mortality, and can affect every major organ system in the body. The three main areas of neurosurgic interest in trauma are TBI, spine and spinal cord injury (SCI), and peripheral nerve injury.

FIG. 41-5. Maturing cerebellar stroke seen as a hypodense area in the right cerebellar hemisphere on head CT in a patient with rapidly progressing obtundation 2 days after the initial onset of symptoms. Swelling of the infarcted tissue causes posterior fossa mass effect. The fourth ventricle is obliterated and not visible, and the brain stem is being compressed.

Head Trauma Glasgow Coma Scale (GCS) Score The initial assessment of the trauma patient includes the primary survey, resuscitation, secondary survey, and definitive care. Neurosurgical evaluation begins during the primary survey with the determination of the GCS score (usually referred to simply as the GCS) for the patient. The GCS is determined by adding the scores of the best responses of the patient in each of the three categories. The motor score ranges from 1 to 6, verbal from 1 to 5, and eyes from 1 to 4. The GCS therefore ranges from 3 to 15, as detailed in Table 41-2.

Scalp Injury Blunt or penetrating trauma to the head can cause injury to the densely vascularized scalp, and significant blood loss can occur. Direct pressure initially controls the bleeding, allowing close inspection of the injury. If a simple laceration is found, it should be copiously irrigated and closed primarily. If the laceration is short, a single-layer percutaneous suture closure will suffice. If the laceration is long or has multiple arms, the patient may need d´ebridement and closure in the operating room, with its superior lighting and wider selection of instruments and suture materials. Careful reapproximation of the galea will provide a more secure closure and better hemostasis. Blunt trauma can also cause crush injury with subsequent tissue necrosis. These wounds require d´ebridement and consideration of advancement flaps to cover the defect.

Skull Fractures The usual classification system for bone fractures may be applied to the skull. Characterization may be done using skull x-rays or head CT.2 A closed fracture is covered by intact skin. An open, or compound, fracture is associated with disrupted overlying skin. The

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A

B

C

FIG. 41-6. A . Head CT scan of a patient with a 4-day-old stroke that occluded the right middle cerebral and posterior cerebral arteries. The infarcted tissue is the hypodense (dark) area indicated by the arrowheads. The patient presented with left-sided weakness and left visual field loss, but then became less responsive, prompting this head CT. Note the right-to-left midline shift. B . Same patient status postdecompressive right hemicraniectomy. Note the free expansion of swollen brain outside the normal confines of the skull. C . Patient with a right middle cerebral artery ischemic stroke with areas of hemorrhagic conversion, seen as hyperdense (bright) areas within the infarcted tissue. This patient also required hemicraniectomy for severe mass effect. Note the lack of midline shift postoperatively.

fracture lines may be single (linear); multiple and radiating from a point (stellate); or multiple, creating fragments of bone (comminuted). Closed skull fractures do not normally require specific treatment. Open fractures require repair of the scalp. Skull fractures in general indicate that a significant amount of force was transmitted to the head, and should increase the suspicion for intracranial injury. Fractures that cross meningeal arteries can cause rupture of the artery and subsequent epidural hematoma formation.

Depressed skull fractures may result from a focal injury of significant force. The inner and outer cortices of the skull are disrupted, and a fragment of bone is pressed in toward the brain in relation to adjacent intact skull. The fragment may overlap the edge of intact bone, or may plunge completely below the level of adjacent normal skull. The inner cortex of the bone fragments often has multiple sharp edges that can lacerate dura, brain, and vessels. Craniotomy is required to elevate the fracture, repair dural disruption, and obtain

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A

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B FIG. 41-7. A . Bone-window axial head CT of a patient who presented aphasic after being struck with the bottom of a beer bottle. CT demonstrates a depressed skull fracture in the left posterior temporoparietal area. B . Brain-window axial head CT demonstrating intraparenchymal hematoma caused by laceration of cortical vessels by the edge of the fractured bone. Arrowhead indicates traumatic subarachnoid hemorrhage in the sylvian fissure.

hemostasis in these cases (Fig. 41-7). Fractures overlying dural venous sinuses require restraint. Surgical exploration can lead to lifethreatening hemorrhage from the lacerated sinus. Fractures of the skull base are common in head-injured patients, and they indicate significant impacts. They are generally apparent on routine head CT, but should be evaluated with dedicated fine-slice coronal-section CT scan to document and delineate the extent of the fracture and involved structures. If asymptomatic, they require no treatment. Symptoms from skull base fractures include cranial nerve deficits and CSF leaks. A fracture of the temporal bone, for instance, can damage the facial or vestibulocochlear nerve, resulting in vertigo, ipsilateral deafness, or facial paralysis. A communication may be formed between the subarachnoid space and the middle ear, allowing CSF drainage into the pharynx via the eustachian tube or from the ear (otorrhea). Extravasation of blood results in ecchymosis behind the ear, known as Battle’s sign. A fracture of the anterior skull base can result in anosmia (loss of smell from damage to the olfactory nerve), CSF drainage from the nose (rhinorrhea), or periorbital ecchymoses, known as raccoon eyes. Copious clear drainage from the nose or ear makes the diagnosis of CSF leakage obvious. Often, however, the drainage may be discolored with blood or small in volume if some drains into the throat. The halo test can help differentiate. Allow a drop of the fluid to fall on an absorbent surface such as a facial tissue. If blood is mixed with CSF, the drop will form a double ring, with a darker center spot containing blood components surrounded by a light halo of CSF. If this is indeterminate, the fluid can be sent to the lab for betatransferrin testing. Beta-transferrin testing will only be positive if CSF is present.

Many CSF leaks will heal with elevation of the head of the bed for several days. A lumbar drain can augment this. A lumbar drain is a catheter placed in the lumbar CSF cistern to decompress the cranial vault and allow the defect to heal by eliminating normal hydrostatic pressure. There is no proven efficacy of antibiotic coverage for preventing meningitis in patients with CSF leaks. Traumatic cranial neuropathies are generally managed conservatively, with documentation of the extent of impairment and signs of recovery. Patients with traumatic facial nerve palsies may benefit from a course of steroids, although their benefit is unproven. Patients with facial nerve palsy of abrupt onset, who do not respond to steroids within 48 to 72 hours may be considered for surgical decompression of the petrous portion of the facial nerve. Patients may also present with delayed-onset facial nerve palsy. Again, steroids are employed and surgery is considered, with mixed results.

Closed Head Injury Closed head injury (CHI) is the most common type of TBI, and a significant cause of morbidity and mortality in the United States. There are two important factors that affect the outcome in CHI and TBI in general. The initial impact causes the primary injury, defined as the immediate injury to neurons from transmission of the force of impact. The long, delicate axons of the neurons can shear as the different areas of the brain through which they pass accelerate and decelerate at different speeds. Prevention strategies, such as wearing helmets, remain the best means to decrease disability from primary injury. Subsequent neuronal damage due to the sequelae of trauma is referred to as secondary injury. Hypoxia, hypotension, hydrocephalus, intracranial hypertension, and intracranial hematoma are

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all mechanisms of secondary injury. The focus of basic research into brain trauma, critical care medicine, and neurosurgical intervention is to decrease the effects of secondary injury. The Brain Trauma Foundation released, with the approval of the American Association of Neurological Surgeons, an updated summary of management recommendations for brain-injured patients in 2000. The guidelines standardize the care of these patients with the hope of improving outcomes. Some of the common patterns of CHI, including concussion, contusion, and diffuse axonal injury, are discussed below.

Initial Assessment. The initial evaluation of a trauma patient remains the same whether or not the primary surveyor suspects head injury. The first three elements of the ABCDs of resuscitation, airway, breathing, and circulation, must first be assessed and stabilized. Hypoxia and hypotension worsen outcome in TBI (due to secondary injury), so cardiopulmonary stabilization is critical. Patients who cannot follow commands require intubation for airway protection and ventilatory control. The fourth element, assessment of the D, for disability, is undertaken next. Motor activity, speech, and eye opening can be assessed in a few seconds and a GCS assigned. An efficient way for the primary surveyor to assess disability and ascertain the status of the three components of the GCS follows. Approach the patient and enter his or her field of view. Observe whether the patient visually orients to you. Clearly command: “Tell me your name.” Then ask the patient to lift up two fingers on each side sequentially, and wiggle the toes. A patient not responsive to these prompts should be assessed for response to deep central painful stimulus, with a firm, twisting pinch of the sensitive skin above the clavicle. Watch for eye opening and movement of the extremities, whether purposeful or reflex. Assess the verbal response. The motor, verbal, and eye-opening scores may be correctly assigned using this rapid examination, and an initial assessment of the probability of significant head injury made. Also take note of any external signs of head injury, including bleeding from the scalp, nose, or ear, or deformation of the skull or face. Medical Management. Several medical steps may be taken to minimize secondary neuronal injury and the systemic consequences of head injury. Patients with a documented closed head injury should receive a 17-mg/kg phenytoin loading dose, followed by 1 week of therapeutic maintenance phenytoin, typically 300 to 400 mg/d. Phenytoin prophylaxis has been shown to decrease the incidence of early posttraumatic seizures. There is no evidence to support longer-term use of prophylactic antiepileptic agents. Blood glucose levels should be closely monitored by free blood sugar checks and controlled with sliding scale insulin. Fevers should also be evaluated and controlled with antipyretics, as well as sourcedirected therapy when possible. Hyperglycemia and hyperthermia are toxic to injured neurons, and so contribute to secondary injury. Head-injured patients have an increased prevalence of peptic ulceration and gastrointestinal (GI) bleeding. Peptic ulcers occurring in patients with head injury or high ICP are referred to as Cushing’s ulcers, and may be related to hypergastrinemia. Ulcer prophylaxis should be used. Compression stockings or athrombic pumps should be used when the patient cannot be mobilized rapidly. Classification. Head injury can be classified as mild, moderate, or severe. For patients with a history of head trauma, classification is as follows: severe head injury if the GCS is 3 to 8, moderate head injury if the GCS is 9 to 12, and mild head injury if the GCS is 13 to 15. Many people present to emergency rooms and trauma bays

with a history of head trauma, so a triage system must be employed to maximize resource utilization while minimizing the chance of missing occult or progressing injuries. Head trauma patients who are asymptomatic; who have only headache, dizziness, or scalp lacerations or abrasions; or who did not lose consciousness have a low risk for intracranial injury and may be discharged home without a head CT scan.3,4 Head-injured patients who are discharged should be sent home with reliable family or friends who can observe the patient for the first postinjury day. Printed discharge instructions, which describe monitoring for confusion, persistent nausea, weakness, or speech difficulty, should be given to the caretaker. The patient should return to the emergency department for evaluation of such symptoms. Patients with a history of altered or lost consciousness, amnesia, progressive headache, skull or facial fracture, vomiting, or seizure have a moderate risk for intracranial injury and should undergo prompt head CT. If the CT is normal, and the neurologic exam has returned to baseline (excluding amnesia of the event), then the patient can be discharged to the care of a responsible adult, again with printed criteria for returning to the ER. Otherwise the patient must be admitted for a 24-hour observation period. Patients with depressed consciousness, focal neurologic deficits, penetrating injury, depressed skull fracture, or changing neurologic exam have a high risk for intracranial injury. These patients should undergo immediate head CT and admission for observation or intervention as needed.

Concussion. A concussion is temporary neuronal dysfunction after nonpenetrating head trauma. The head CT is normal, and deficits resolve over minutes to hours. Definitions vary; some require transient loss of consciousness, while others include patients with any alteration of mental status. Memory difficulties, especially amnesia of the event, are very common. Concussions may be graded. One method is the Colorado Medical Society system. Head trauma patients with confusion only are grade 1, patients with amnesia are grade 2, and patients who lose consciousness are grade 3. Studies have shown that the brain remains in a hypermetabolic state for up to a week after injury. The brain is also much more susceptible to injury from even minor head trauma in the first 1 to 2 weeks after concussion. This is known as second-impact syndrome, and patients should be informed that even after mild head injury they might experience memory difficulties or persistent headaches.5 Contusion. A contusion is a bruise of the brain, and occurs when the force from trauma is sufficient to cause breakdown of small vessels, and extravasation of blood into the brain. The contused areas appear bright on CT scan, as seen in Fig. 41-8. The frontal, occipital, and temporal poles are most often involved. The brain sustains injury as it moves in relation to rough bony surfaces. Contusions themselves rarely cause significant mass effect as they represent small amounts of blood in injured parenchyma rather than coherent blood clots. Edema may develop around a contusion, causing mass effect. Contusions may also enlarge, or develop a true hematoma, especially during the first 24 hours. Contusions may also be seen in brain tissue opposite the site of impact. This is known as a contre coup injury. These contusions result from deceleration of the brain against the skull. Diffuse Axonal Injury. Diffuse axonal injury is caused by damage to axons throughout the brain, due to rotational acceleration and then deceleration. Axons may be completely disrupted and then retract, forming axon balls. Small hemorrhages can be seen in more

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results from arterial disruption, especially of the middle meningeal artery. The dura is adherent to bone and some pressure is required to dissect between the two. EDH has a classic three-stage clinical presentation that is probably seen in only 20% of cases. The patient is initially unconscious from the concussive aspect of the head trauma. The patient then awakens and has a lucid interval while the hematoma subclinically expands. As the volume of the hematoma grows, the decompensated region of the pressure-volume curve is reached, the ICP increases, and the patient becomes lethargic and herniates. Uncal herniation from an EDH classically causes ipsilateral third nerve palsy and contralateral hemiparesis. On head CT the clot is bright, biconvex (lentiform), and has a well-defined border that usually respects cranial suture lines. The clot generally forms over the convexities, but may rarely occur in the posterior fossa as well. Open craniotomy for evacuation of the congealed clot and hemostasis is indicated for EDH, except in selected cases of asymptomatic clots that are less than 1 cm in maximum thickness, seen in patients with a negative neurologic examination. Prognosis after successful evacuation is better for epidural hematoma than subdural hematoma. EDHs are associated with lower-energy trauma with less resultant primary brain injury. Good outcomes may be seen in 85 to 90% of patients, with rapid CT scan and intervention.

FIG. 41-8. Severe bilateral contusions in the basal aspect of the frontal lobes, caused by the brain moving over the rough, irregular skull base during sudden cranial acceleration.

severe cases, especially on MRI. Hemorrhage is classically seen in the corpus callosum and the dorsolateral midbrain.

Penetrating Injury. These are complex and must be evaluated individually. The two main subtypes are missile injury (e.g., due to bullets or fragmentation devices) and nonmissile injury (e.g., due to knives or ice picks). Some general principles do apply. If available, skull x-rays and CT scans are useful in assessing the nature of the injury. Cerebral angiography must be considered if the object passes near a major artery or dural venous sinus. Operative exploration is necessary to remove any object extending out of the cranium, as well as for d´ebridement, irrigation, hemostasis, and definitive closure. Small objects contained within brain parenchyma are often left in place to avoid iatrogenic secondary brain injury. Antibiotics are given to decrease the chances of meningitis or abscess formation. High-velocity missile injuries (from high-powered hunting rifles or military weapons) are especially deadly, because the associated shock wave causes cavitary tissue destruction of an area that is much larger than the projectile itself. Projectiles that penetrate both hemispheres or traverse the ventricles are almost universally fatal. Traumatic Intracranial Hematomas The various traumatic intracranial hematomas contribute to death and disability secondary to head injury. Hematomas can expand rapidly and cause brain shifting and subsequent herniation. Emergent neurosurgical evaluation and intervention are often necessary.

Epidural Hematoma. Epidural hematoma (EDH) is the accumulation of blood between the skull and the dura. EDH usually

Acute Subdural Hematoma. An acute subdural hematoma (SDH) is the result of an accumulation of blood between the arachnoid membrane and the dura. Acute SDH usually results from venous bleeding, usually from tearing of a bridging vein running from the cerebral cortex to the dural sinuses. The bridging veins are subject to stretching and tearing during acceleration/deceleration of the head, because the brain shifts in relation to the dura, which firmly adheres to the skull. Elderly and alcoholic patients are at higher risk for acute SDH formation after head trauma due to the greater mobility of their atrophied brains within the cranial vault. On head CT scan, the clot is bright or mixed-density, crescentshaped (lunate), may have a less distinct border, and does not cross the midline due to the presence of the falx. Most SDHs are over the cerebral hemispheres, but they may also layer on the tentorium or be interhemispheric. Open craniotomy for evacuation of the clot is indicated for any acute SDH more than 1 cm in thickness, or smaller hematomas that are symptomatic. Symptoms may be as subtle as a contralateral pronator drift, or as dramatic as coma. Smaller hematomas may stabilize and eventually reabsorb, or become chronic SDHs. Nonoperatively managed patients require frequent neurologic exams until stabilization of the clot if proven by serial head CT scans. The prognosis for functional recovery is significantly worse for acute SDH than EDH, because it is associated with greater primary injury to brain parenchyma from high-energy impacts. Prompt recognition and intervention minimizes secondary injury. Elderly patients, patients with low admission GCS, or high postoperative ICP do poorly, with as few as 5% attaining functional recovery.6 Chronic Subdural Hematoma. Chronic SDH is a collection of blood breakdown products that is at least 3 weeks old. Acute hematomas are bright white (hyperdense) on CT scan for approximately 3 days, after which they fade to isodensity with brain, and then to hypodensity after 2 to 3 weeks. A true chronic SDH will be as dark as CSF on CT. Traces of white are often seen due to small hemorrhages into the collection. These small bleeds may expand the collection enough to make it symptomatic. This is referred to as acute-on-chronic SDH. Figure 41-9 demonstrates the CT

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to allow simple conversion to craniotomy, and the incisions and burr holes placed to allow easy incorporation into question mark–shaped craniotomy flaps. There are various strategies to prevent reaccumulation of blood. Subdural or subgaleal drains may be left in place for 1 to 2 days. Mild hydration and bedrest with the head of bed flat may encourage brain expansion. High levels of inspired oxygen may help draw nitrogen out of the cavity. Regardless of the strategy used, follow-up head CT scans are required immediately postoperatively and approximately 1 month later to document resolution.

Intraparenchymal Hemorrhage. Isolated hematomas within the brain parenchyma are more often associated with hypertensive hemorrhage or arteriovenous malformations. Bleeding may occur in a contused area of brain. Mass effect from developing hematomas may present as delayed neurologic deficit. Delayed traumatic intracerebral hemorrhage is most likely to occur within the first 24 hours. Patients with contusion on the initial head CT scan should be reimaged 24 hours after the trauma to document stable pathology. Vascular Injury

FIG. 41-9. Head CT scan of an elderly patient with progressing left hemiplegia and lethargy, demonstrating an acute-on-chronic subdural hematoma. History revealed that the patient sustained a fall 4 weeks prior to presentation. Arrowheads outline the hematoma. The acute component is slightly denser, and is seen as the hyperdense area in the dependent portion.

appearance of an acute-on-chronic SDH. Vascularized membranes form within the hematoma as it matures. These membranes may be the source of acute hemorrhage. Chronic SDHs often occur in patients without a clear history of head trauma, as they may arise from minor trauma. Alcoholics, the elderly, and patients on anticoagulation are at higher risk for developing chronic SDH. Patients may present with headache, seizure, confusion, contralateral hemiparesis, or coma. A chronic SDH thicker than 1 cm, or any symptomatic SDH should be surgically drained. Unlike acute SDH, which consists of a thick, congealed clot, chronic SDH typically consists of a viscous fluid, with a texture and the dark brown color reminiscent of motor oil. As such, a simple burr hole can effectively drain most chronic SDHs. There remains controversy about the optimum treatment of chronic SDH, but most authorities agree that burr hole drainage should be attempted first, to obviate the risks of formal craniotomy. A single burr hole placed over the dependent edge of the collection can be made, and the space copiously irrigated until the fluid is clear. A second, more anterior, burr hole can then be placed if the collection does not drain satisfactorily due to containment by membranes. The procedure is converted to open craniotomy if the SDH is too congealed for irrigation drainage, the complex of membranes prevents effective drainage, or persistent hemorrhage occurs that cannot be reached with bipolar cautery through the burr hole. The required surgical prepping and draping are always performed

Trauma to the head or neck may cause damage to the carotid or vertebrobasilar systems. In general usage, dissection refers to violation of the vessel wall intima. Blood at arterial pressure can then open a plane between the intima and media, within the media, or between the media and adventitia. The newly created space within the vessel wall is referred to as the false lumen. Tissue or organs supplied by traumatically-dissected vessels may subsequently be injured in several ways. Expansion of the hematoma within the vessel wall can lead to narrowing of the true vessel lumen and reduction or cessation of distal blood flow. Slow-flowing or stagnant blood within the false lumen exposed to thrombogenic vessel wall elements may thrombose. Pieces of thrombus may then detach and cause distal embolic arterial occlusion. Also, the remaining partial-thickness vessel wall may rupture, damaging adjacent structures. Traumatic dissection may occur in the carotid artery (anterior circulation) or the vertebral or basilar arteries (posterior circulation). Dissections may be extradural or intradural. Intradural dissection can present with subarachnoid hemorrhage, whereas extradural dissection cannot. Traditional angiography remains the basis of diagnosis and characterization of arterial dissection. Angiographic abnormalities include stenosis of the true lumen, visible intimal flaps, and the appearance of contrast in the false lumen. Four-vessel cerebral angiography should be performed when suspicion of dissection exists. Patients with documented arterial dissection should be anticoagulated with heparin and then warfarin to prevent thromboembolic stroke. Trauma patients often have concomitant absolute or relative contraindications to anticoagulation, complicating management. Warfarin may be discontinued when the angiogram normalizes, or after several months. Consider surgical intervention for persisting embolic disease and for vertebral dissections presenting with subarachnoid hemorrhage. Surgical options include vessel ligation and bypass grafting. Interventional radiology techniques include stenting and vessel occlusion. Occlusion techniques depend on good collateral circulation to perfuse the vascular territory previously supplied by the occluded vessel.

Carotid Dissection. Carotid dissection may result from neck extension combined with lateral bending to the opposite side, or trauma from an incorrectly placed shoulder belt tightening across

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the neck in a motor vehicle accident. Extension/bending stretches the carotid over the bony transverse processes of the cervical vertebrae, while seat belt injuries cause direct trauma. Symptoms of cervical carotid dissection include contralateral neurologic deficit from brain ischemia, headache, and ipsilateral Horner’s syndrome from disruption of the sympathetic tracts ascending from the stellate ganglion into the head on the surface of the carotid artery. The patient may complain of hearing or feeling a bruit. Traumatic vessel wall injury to the portion of the carotid artery running through the cavernous sinus may result in a carotidcavernous fistula (CCF). This creates a high-pressure, high-flow pathophysiologic blood flow pattern. CCFs classically present with pulsatile proptosis (the globe pulses outward with arterial pulsation), retro-orbital pain, and decreased visual acuity or loss of normal eye movement (due to damage to cranial nerves III, IV, and VI as they pass through the cavernous sinus). Symptomatic CCFs should be treated to preserve eye function. Fistulae may be closed by balloon occlusion using interventional neuroradiology techniques. Fistulae with wide necks are difficult to treat and may require total occlusion of the parent carotid artery.

Vertebrobasilar Dissection. Vertebrobasilar dissection may result from sudden rotation or flexion/extension of the neck, chiropractic manipulation, or a direct blow to the neck. Common symptoms are neck pain, headache, and brain stem stroke or subarachnoid hemorrhage. Treatment is as described above. Brain Death Brain death occurs when there is an absence of signs of brain stem function or motor response to deep central pain in the absence of pharmacologic or systemic medical conditions that could impair brain function.

Clinical Examination. A neurologist, neurosurgeon, or intensivist generally performs the clinical brain death exam. Two exams consistent with brain death 12 hours apart, or one exam consistent with brain death followed by a consistent confirmatory study is generally sufficient to declare brain death (see below). Hospital regulations and local laws regarding documentation should be followed closely. Establish the absence of complicating conditions before beginning the exam. The patient must be normotensive, euthermic, and oxygenating well. The patient may not be under the effects of any sedating or paralytic drugs. Documentation of no brain stem function includes the following: nonreactive pupils; lack of corneal blink, oculocephalic (doll’s eyes), or oculovestibular (cold calorics) reflexes; and loss of drive to breathe (apnea test). The apnea test demonstrates no spontaneous breathing even when Paco2 is allowed to rise above 60 mm Hg. Deep central painful stimulus is provided by forceful twisting pinch of the sensitive skin above the clavicle. Pathologic responses such as flexor or extensor posturing are not compatible with brain death. Spinal reflexes to peripheral pain, such as triple flexion of the lower extremities, are compatible with brain death. Confirmatory Studies. Confirmatory studies are performed after a documented clinical exam consistent with brain death. A study consistent with brain death may obviate the need to wait 12 hours for a second exam. This is especially important when the patient is a potential organ donor, as brain dead patients often have progressive hemodynamic instability. Lack of cerebral blood flow consistent with brain death may be documented by cerebral angiography or technetium radionuclide study. A “to-and-fro” pattern

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on transcranial Doppler (TCD) ultrasonography indicates no net forward flow through the cerebral vasculature, consistent with brain death. An electroencephalogram (EEG) documenting electrical silence has been used, but is generally not favored because there is often artifact or noise on the recording. This can confuse the situation and be especially difficult for families to understand.

Spine Trauma The spine is a complex biomechanic and neural structure. The spine provides structural support for the body as the principal component of the axial skeleton, while protecting the passing spinal cord and nerve roots. Trauma may fracture bones or cause ligamentous disruption. Often bone and ligament damage occur together. Damage to these elements reduces the strength of the spine and may cause the spine to be unstable. This compromises both its structural support function and its ability to protect neural elements. Spine trauma may occur with or without neurologic injury. Neurologic injury from spine trauma is classified as either incomplete, if there is some residual motor or sensory neurologic function below the level of the lesion, or complete, if there is no residual neurologic function below the level of the lesion, as assessed by clinical exam.7 A patient with complete neurologic dysfunction persisting 24 hours after injury has a very low probability of return of function in the involved area. Neurologic injury from spine trauma may occur immediately or in delayed fashion. Immediate neurologic injury may be due to direct damage to the spinal cord or nerve roots from penetrating injuries, especially from stab wounds or gunshots. Blunt trauma may transfer sufficient force to the spine to cause acute disruption of bone and ligament and lead to subluxation, which is shift of one vertebral element in relation to the adjacent level. Subluxation decreases the size of the spinal canal and neural foramina, and causes compression of the cord or roots. Such neural impingement can also result from propulsion of bone fragments into the canal during a fracture. Transection, crush injury, and cord compression impairing perfusion are mechanisms leading to spinal cord injury. Delayed neurologic injury may occur during transportation or examination of a patient who is not properly immobilized.

The Mechanics of Spine Trauma Trauma causes a wide variety of injury patterns in the spine due to its biomechanic complexity. A mechanistic approach facilitates an understanding of the patterns of injury, as there are only a few types of forces that can be applied to the spine. Although these forces are discussed individually, they often occur in combination. Several of the most common injury patterns are then presented to illustrate the clinical results of these forces and combinations of forces applied at pathologically high levels.

Flexion/Extension. Bending the head and body forward into a fetal position flexes the spine. Flexion loads the spine anteriorly (the vertebral bodies) and distracts the spine posteriorly (the spinous process and interspinous ligaments). High flexion forces occur during front-end motor vehicle collisions, and backward falls when the head strikes first. Arching the neck and back extends the spine. Extension loads the spine posteriorly and distracts the spine anteriorly. High extension forces occur during rear-end motor vehicle collisions (especially if there is no headrest), frontward falls when the head strikes a first, or diving into shallow water. Compression/Distraction. Force applied along the spinal axis (axial loading) compresses the spine. Compression loads the

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spine anteriorly and posteriorly. High compression forces occur when a falling object strikes the head or shoulders, or when landing on the feet, buttocks, or head after a fall from height. A pulling force in line with the spinal axis distracts the spine. Distraction unloads the spine anteriorly and posteriorly. Distraction forces occur during a hanging, when the chin or occiput strikes an object first during a fall, or when a passenger submarines under a loose seat belt during a front-end motor vehicle collision.

Rotation. Force applied tangential to the spinal axis rotates the spine. Rotation depends on the range of motion of intervertebral facet joints. High rotational forces occur during off-center impacts to the body or head or during glancing automobile accidents. Patterns of Injury Certain patterns of injury resulting from the forces described above or from combinations of those forces occur commonly and should be recognized during plain film imaging of the spine. Always completely evaluate the spine. A patient with a spine injury at one level is at significant risk for additional injuries at other levels.

Cervical. The cervical spine is more mobile than the thoracolumbar spine. Stability comes primarily from the multiple ligamentous connections of adjacent vertebral levels. Disruption of the cervical ligaments can lead to instability in the absence of fracture. The mass of the head transmits significant forces to the cervical spine during abrupt acceleration or deceleration, increasing risk for injury. Jefferson Fracture. Jefferson’s fracture is a bursting fracture of the ring of C1 (the atlas) due to compression forces. There are usually two or more fractures through the ring of C1. The openmouth odontoid view may show lateral dislocation of the lateral masses of C1. The rule of Spence states that 7 mm or greater combined dislocation indicates disruption of the transverse ligament. The transverse ligament stabilizes C1 with respect to C2. Jefferson fractures dislocated less than 7 mm are usually treated with a rigid collar, while those dislocated 7 mm or greater are usually treated with a halo vest. Surgical intervention is not indicated. Odontoid Fractures. The odontoid process, or dens, is the large ellipse of bone arising anteriorly from C2 (the axis) and projecting up through the ring of C1 (the atlas). Several strong ligaments connect the odontoid to C1 and to the base of the skull. Odontoid fractures usually result from flexion forces. Odontoid fractures are classified as type I, II, or III. A type I fracture involves the tip only. A type II fracture passes through the base of the odontoid process. A type III fracture passes through the body of C2. Types I and II are considered unstable and should be externally immobilized by a halo vest or fused surgically. Surgery is often undertaken for widely displaced fractures (poor chance of fusing) and for those that fail external immobilization. Type III fractures usually fuse with external immobilization only. Hangman’s Fracture. Traditionally considered a hyperextension/distraction injury from placement of the noose under the angle of the jaw, hangman’s fractures may also occur with hyperextension/compression, as with diving accidents, or hyperflexion. Its definition is bilateral C2 pars interarticularis fracture. The pars interarticularis is the bone between superior and inferior facet joints. The bony connection between C1 and C3 is lost. Hangman’s fractures heal well with external immobilization. Surgery is indicated if there is spinal cord compression or after failure of external immobilization.

Jumped Facets—Hyperflexion Injury. The facet joints of the cervical spine slope forward, and the facet from the level above can slide up and forward over the facet from the level below if the joint capsule is torn. Hyperflexion/rotation can cause a unilateral jumped facet, whereas straight hyperflexion leads to bilateral jumped facets. Patients with a unilateral injury are usually neurologically intact, while those with bilateral injury usually have spinal cord damage. The anteroposterior diameter of the spinal canal decreases more with bilateral injury, leading to spinal cord compression (Fig. 41-10).

Thoracolumbar. The thoracic spine is significantly stabilized by the rib cage. The lumbar spine has comparatively very large vertebrae. Thus the thoracolumbar spine has a higher threshold for injury than the cervical spine. The three-column model is useful for categorizing thoracolumbar injuries. The anterior longitudinal ligament and the anterior half of the vertebral body constitute the anterior column. The posterior half of the vertebral body and the posterior longitudinal ligament constitute the middle column. The pedicles, facet joints, laminae, spinous processes, and interspinous ligaments constitute the posterior column. Compression Fracture. This is a compression/flexion injury causing failure of the anterior column only. It is stable and not associated with neurologic deficit, although the patient may still have significant pain (Fig. 41-11). Burst Fracture. This is a pure axial compression injury causing failure of the anterior and middle columns. It is unstable, and perhaps half of patients have neurologic deficit due to compression of the cord or cauda equina from bone fragments retropulsed into the spinal canal. Chance Fracture. This is a flexion-distraction injury causing failure of the middle and posterior columns. It is typically unstable and is often associated with neurologic deficit. Fracture-Dislocation. This is failure of the anterior, middle, and posterior columns caused by flexion/distraction, shear, or compression forces. Neurologic deficit can result from retropulsion of middle column bone fragments into the spinal canal, or from subluxation causing decreased canal diameter (Fig. 41-12). Initial Assessment and Management The possibility of a spine injury must be considered in all trauma patients. A patient with no symptoms referable to neurologic injury, a normal neurologic exam, no neck or back pain, and a known mechanism of injury unlikely to cause spine injury is at minimal risk for significant injury to the spine. Victims of moderate or severe trauma, especially those with injuries to other organ systems, usually fail to meet these criteria or cannot be assessed adequately. The latter is often due to impaired sensorium or significant pain. Because of the potentially catastrophic consequences of missing occult spine instability in a neurologically intact patient, a high level of clinical suspicion should govern patient care until completion of clinical and radiographic evaluation. The trauma patient should be kept on a hard flat board with straps and pads used for immobilization. A hard cervical collar is kept in place. These steps minimize forces transferred through the spine, and therefore decrease the chance of causing dislocation, subluxation, or neural compression during transport to the trauma bay. The patient is then moved from the board to a flat stretcher. The primary survey and resuscitation are completed. Physical exam and initial x-rays follow. For the exam, approach the patient as described in the section on neurologic examination earlier in this chapter. Evaluation for spine or spinal cord injury is easier and more informative in awake

A

C B

D FIG. 41-10. A . Lateral cervical spine x-ray of an elderly woman who struck her head during a backward fall. Arrowhead points to jumped facets at C5–C6. Note the anterior displacement of the C5 body with respect to the C6 body. B . Sagittal T2-weighted MRI of the same patient, revealing compromise of the spinal canal and compression of the cord. Note the bright signal within the cord at the level of compression, indicating spinal cord injury. C . Lateral cervical spine x-ray of same patient after application of cervical traction and manual reduction. Note restoration of normal alignment. D . Lateral cervical spine x-ray after posterior cervical fusion to restabilize the C5–C6 segment of the spine.

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A

B

FIG. 41-11. A . Lateral lumbar spine x-ray showing a compression fracture of L2. Note the posterior wall of the vertebral body has retained normal height and alignment. B . Axial CT scan through the same fracture. Arrowhead demonstrates a transverse discontinuity in the superior endplate of the L2 body.

patients. If the patient is awake, ask if he or she recalls details of the nature of the trauma, and if there was loss of consciousness, numbness, or inability to move any or all limbs. Assess motor function by response to commands or pain, as appropriate. Assess pinprick, light touch, and joint position if possible. Determining the anatomically lowest level of intact sensation can pinpoint the level of the lesion along the spine. Test sensation in an ascending fashion, as the patient will be better able to note when he or she first feels the stimulus, rather than when he or she can no longer feel it. Document muscle stretch reflexes, lower sacral reflexes (i.e., anal wink and bulbocavernosus), and rectal tone.

American Spinal Injury Association Classification. The American Spinal Injury Association (ASIA) provides a method of classifying patients with spine injuries. The classification indicates completeness and level of the injury and the associated deficit. A form similar to that shown in Fig. 41-13 should be available in the trauma bay and completed for any spine injury patient. The association also has worked to develop recommendations and guidelines to standardize the care of SCI patients in an effort to improve the quality of care.

Neurologic Syndromes Penetrating, compressive, or ischemic cord injury can lead to several characteristic presentations based on the anatomy of injury. The neurologic deficits may be deduced from the anatomy of the

long sensory and motor tracts and understanding of their decussations (Fig. 41-14). Four patterns are discussed. First, injury to the entire cord at a given level results in anatomic or functional cord transection with total loss of motor and sensory function below the level of the lesion. The typical mechanism is severe traumatic vertebral subluxation reducing spinal canal diameter and crushing the cord. Second, injury to half the cord at a given level results in BrownSequard syndrome, with loss of motor control and proprioception ipsilaterally, and loss of nociception and thermoception contralaterally. The typical mechanism is a stab or gunshot wound. Third, injury to the interior of the cord results in central cord syndrome, with upper extremity worse than lower extremity weakness and varying degrees of numbness. The typical mechanism is transient compression of the cervical cord by the ligamentum flavum buckling in posteriorly during traumatic neck hyperextension. This syndrome occurs in patients with preexisting cervical stenosis. Fourth, injury to the ventral half of the cord results in anterior cord syndrome, with paralysis and loss of nociception and thermoception bilaterally. The typical mechanism is acute disc herniation or ischemia from anterior spinal artery occlusion.

Studies Anteroposterior (AP) and lateral plain films provide a rapid survey of the bony spine. Plain films detect fractures and dislocations well. Adequate visualization of the lower cervical and upper thoracic spine is often impossible because of the shoulder girdle. Complete

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plain film imaging of the cervical spine includes an open-mouth odontoid view to assess the odontoid and the lateral masses of C1. Fine-slice CT scan with sagittal and coronal reconstructions provides good detail of bone anatomy, and is good for characterizing fractures seen on plain films, as well as visualizing C7–T1 when not well seen on plain films. MRI provides the best soft tissue imaging. Canal compromise from subluxation, acute disc herniations, or ligamentous disruption is clearly seen. MRI also may detect damage to the spinal cord itself, including contusions or areas of ischemia.

Definitive Management

FIG. 41-12. Sagittal reconstruction of an axial fine-slice CT scan through the lumbar spine demonstrating a severe fracture-dislocation through the body of L2.

A

Spinal-Dose Steroids. The National Acute Spinal Cord Injury Study (NASCIS) I and II papers provide the basis for the common practice of administering high-dose steroids to patients with acute spinal cord injury. A 30-mg/kg IV bolus of methylprednisolone is given over 15 minutes, followed by a 5.4-mg/kg per hour infusion begun 45 minutes later. The infusion is continued for 23 hours if the bolus is given within 3 hours of injury, or for 47 hours if the bolus is given within 8 hours of injury. The papers indicate greater motor and sensory recovery at 6 weeks, 6 months, and 1 year after acute spinal cord injury in patients who received methylprednisolone.8,9 However, the NASCIS trial data have been extensively criticized, as many argue that the selection criteria and study design were flawed, making the results ambiguous. Patients who receive such a large corticosteroid dose have increased rates of medical and ICU complications, such as pneumonias, which have a deleterious affect on outcome. A clear consensus on the use of spinal-dose steroids does not exist.10 A decision to use or not use spinal-dose steroids may be dictated by local or regional

B FIG. 41-13. The American Spinal Injury Association system for categorizing spinal cord injury patients according to level and degree of neurologic deficit.

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SPINAL CORD SYNDROMES Dorsal column (touch, vibration) Corticospinal tract (upper motor) Anterior horn (lower motor) Spinothalmic tract (pain, temperature)

Transection

Central cord

Brown-Sequard

practice patterns, especially given the legal liability issues surrounding spinal cord injury. Patients with gunshot injuries or nerve root (cauda equina) injury, as well as those on chronic steroid therapy, who are pregnant, or who are less than 14 years old were excluded from the NASCIS studies, and should not receive spinal-dose steroids.

Orthotic Devices. Rigid external orthotic devices can stabilize the spine by decreasing range of motion and minimizing stress transmitted through the spine. Commonly used rigid cervical orthotics include Philadelphia and Miami-J collars. Cervical collars are inadequate for C1, C2, or cervicothoracic instability. Cervicothoracic orthoses (CTOs) brace the upper thorax and the neck, improving stabilization over the cervicothoracic region. Minerva braces improve high cervical stabilization by bracing from the upper thorax to the chin and occiput. Halo-vest assemblies provide the most external cervical stabilization. Four pins driven into the skull lock the halo ring in position. Four posts arising from a tight-fitting rigid plastic vest immobilize the halo ring. Lumbar stabilization may be provided by thoracolumbosacral orthoses (TLSOs). A variety of companies manufacture lines of spinal orthotics. A physician familiar with the technique should fit a halo-vest. Assistance from a trained orthotics technician improves fitting and adjustment of the other devices. Surgery. Neurosurgical intervention has two goals. First is the decompression of the spinal cord or nerve roots in patients with incomplete neurologic deficits. These patients should be decompressed expeditiously, especially if there is evidence of neurologic deterioration over time. Second is the stabilization of injuries judged too unstable to heal with external orthotics only. Spine trauma patients with complete neurologic deficit, without any signs of recovery, or those without any neurologic deficits who have bony or ligamentous injury requiring open fixation, may be medically stabilized before undergoing surgery. Surgical stabilization may be indicated for some injuries that would eventually heal with conservative treatment. Surgical stabilization can allow early mobilization, aggressive nursing care, and physical therapy. Solid surgical stabilization may also allow a patient to be managed with a rigid cervical collar who would otherwise require halo-vest immobilization.

Anterior spinal a.

FIG. 41-14. Spinal cord injury patterns. (Adapted with permission from Hoff J, Boland M: Neurosurgery, from Schwartz’s Textbook of General Surgery, 7th ed. New York: McGraw-Hill, 1999, p 1837.)

Continued Care Regional spinal cord injury centers with nurses, respiratory therapists, pulmonologists, physical therapists, physiatrists, and neurosurgeons specifically trained in caring for these patients may improve outcomes. Frequently encountered ICU issues include hypotension and aspiration pneumonia. Chronically, prevention and treatment of deep venous thrombosis, autonomic hyperreflexia, and decubitus ulcer formation are important. Patients with high cervical cord injuries (C4 or above) will often be terminally ventilator dependent. Many patients with cervical or high thoracic cord injuries require prolonged ventilatory support until the chest wall becomes stiff enough to provide resistance for diaphragmatic breathing. Patients should be transferred to spinal cord injury rehabilitation centers after stabilization of medical and surgical issues.

Peripheral Nerve Trauma The peripheral nervous system extends throughout the body and is subject to injury from a wide variety of traumas. Peripheral nerves transmit motor and sensory information between the CNS and the body. An individual nerve may have pure motor, pure sensory, or mixed motor and sensory functions. The key information-carrying structure of the nerve is the axon. The axon transmits information from the neuronal cell body and may measure from less than 1 mm to greater than 1 m in length. Axons that travel a significant distance are often covered with myelin, which is a lipid-rich, electrically-insulating sheath formed by Schwann cells. Myelinated axons transmit signals much more rapidly than unmyelinated axons, because the voltage shifts and currents that define action potentials effectively jump from gap to gap over the insulated lengths of the axon. Axons, whether myelinated or unmyelinated, travel through a collagenous connective tissue known as endoneurium. Groups of axons and their endoneurium form bundles known as fascicles. Fascicles run through a tubular collagenous tissue known as perineurium. Groups of fascicles are suspended in mesoneurium. Fascicles and their mesoneurium run through another tubular collagenous tissue known as epineurium. The epineurium and its contents form the nerve.

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There are four major mechanisms of injury to peripheral nerves. Nerves may be lacerated, stretched, compressed, or contused. Knives, passing bullets, or jagged bone fractures may lacerate nerves. Adjacent expanding hematomas or dislocated fractures may stretch nerves. Expanding hematomas, external orthoses such as casts or braces, or blunt trauma over a superficial nerve may compress or crush nerves. Shock waves from high-velocity bullets may contuse nerves. These mechanisms of injury cause damage to the various anatomic components of the nerve. The patterns of damage are categorized below. Certain nerve segments are particularly vulnerable to injury. The following four characteristics make a nerve segment more vulnerable: proximity to a joint, superficial course, passage through a confined space, and being fixed in position.

Types of Injury The traditional classification system for peripheral nerve injury is the Seddon classification. Seddon described three injury patterns: neurapraxia, axonotmesis, and neurotmesis, as defined below. The Seddon classification provides a simple, anatomically-based approach to peripheral nerve injury.

Neurapraxia. Neurapraxia is defined as the temporary failure of nerve function without physical axonal disruption. Axon degeneration does not occur. Return of normal axonal function occurs over hours to months, often in the 2- to 4-week range. Axonotmesis. Axonotmesis is the disruption of axons and myelin. The surrounding connective tissues, including endoneurium, are intact. The axons degenerate proximally and distally from the area of injury. Distal degeneration is known as wallerian degeneration. Axon regeneration within the connective tissue pathways can occur, leading to restoration of function. Axons regenerate at a rate of 1 mm per day. Significant functional recovery may occur for up to 18 months. Scarring at the site of injury from connective tissue reaction can form a neuroma and interfere with regeneration. Neurotmesis. Neurotmesis is the disruption of axons and endoneurial tubes. Peripheral collagenous components, such as the epineurium, may or may not be intact. Proximal and distal axonal degeneration occurs. The likelihood of effective axonal regeneration across the site of injury depends on the extent of neuroma formation and on the degree of persisting anatomic alignment of the connective tissue structures. For instance, an injury may damage axons, myelin, and endoneurium, but leave perineurium intact. In this case the fascicle sheath is intact, and appropriate axonal regeneration is more likely to occur than if the sheath is interrupted. Management of Peripheral Nerve Injury The sensory and motor deficits should be accurately documented. Deficits are usually immediate. Progressive deficit suggests a process such as an expanding hematoma, and may need early surgical exploration. Clean, sharp injuries may also benefit from early exploration and reanastomosis. Most other peripheral nerve injuries should be observed. Electromyography and nerve conduction studies (EMG/NCS) should be done 3 to 4 weeks postinjury if deficits persist. Axon segments distal to the site of injury conduct action potentials normally until wallerian degeneration occurs, so EMG/NCS before 3 weeks is not informative. Continue observation if function improves. Explore the nerve surgically if no functional improvement occurs over 3 months. If intraoperative electrical testing reveals conduction across the injury, continue observation. In the absence of conduction, the segment should be resected and end-to-end primary

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anastomosis attempted. Anastomoses under tension will not heal, so a nerve graft may be needed to bridge the gap between the proximal and distal nerve ends. The sural nerve is often harvested, as it carries only sensory fibers and leaves a minor deficit when harvested. The connective tissue structures of the nerve graft may provide a pathway for effective axonal regrowth across the injury.

Patterns of Injury Brachial Plexus. The brachial plexus may be injured in a variety of ways. Parturition or a motorcycle accident can lead to plexus injury due to dislocation of the glenohumeral joint. Attempting to arrest a fall with one’s hands can lead to a stretch injury of the plexus due to abrupt movement of the shoulder girdle. A lung apex tumor, known as a Pancoast tumor, can cause compression injury to the plexus. There are many patterns of neurologic deficits possible with injury to the various components of the brachial plexus, and understanding them all would require extensive neuroanatomic discussion. Two well-known eponymous syndromes are Erb’s palsy and Klumpke’s palsy. Injury high in the plexus to the C5 and C6 roots resulting from glenohumeral dislocation causes Erb’s palsy with the characteristic “bellhop’s tip” position. The arm hangs at the side, internally rotated. Hand movements are not affected. Injury low in the plexus, to the C8 and T1 roots, resulting from stretch or compression injury, causes Klumpke’s palsy with the characteristic “claw hand” deformity. There is weakness of the intrinsic hand muscles, similar to that seen with ulnar nerve injury. Radial Nerve. The radial nerve courses through the axilla, and then laterally and posteriorly in the spiral groove of the humerus. Improper crutch use can cause damage to the axillary portion. The section of the nerve traversing the spiral groove can be damaged by humerus fractures or pressure from improper positioning during sleep. This classically occurs when the patient is intoxicated and is called “Saturday night palsy.” The key finding is wrist drop (i.e., weakness of hand and finger extensors). Axillary (proximal) injury causes tricep weakness in addition to wrist drop. Common Peroneal Neuropathy. The common peroneal nerve forms the lateral half of the sciatic nerve (the medial half being the tibial nerve). It receives contributions from L4, L5, S1, and S2. It emerges as a separate nerve in the popliteal fossa and wraps laterally around the fibular neck, after which it splits to form the deep peroneal nerve and the superficial peroneal nerve. The superficial, fixed location at the fibular neck makes the nerve susceptible to compression. The classic cause of traumatic peroneal neuropathy is crush injury from a car bumper striking the lateral aspect of the leg at the level of the knee. Symptoms of common peroneal neuropathy include foot drop (weakness of the tibialis anterior) and numbness over the anterolateral surface of the lower leg and dorsum of the foot. Surgical exploration of this lesion is typically unsatisfying. Rare cases may be due to compressive fibers or adhesions that may be lysed, with the possibility of return of function. CEREBROVASCULAR DISEASE Cerebrovascular disease is the most frequent cause of new rapidonset, nontraumatic neurologic deficit. It is a far more common etiology than seizures or tumors. Vascular structures are subject to a variety of chronic pathologic processes which compromise vessel wall integrity. Diabetes, high cholesterol, high blood pressure, and smoking are risk factors for vascular disease. These conditions can lead to vascular damage by such mechanisms as atheroma deposition

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causing luminal stenosis, endothelial damage promoting thrombogenesis, and weakening of the vessel wall resulting in aneurysm formation or dissection. These processes may coexist. For instance, a vessel may contain an atheromatous plaque that significantly decreases lumen diameter, and also have compromised endothelium over the plaque, providing the opportunity for thrombus formation, which can lead to acute total occlusion of the remaining lumen. Aneurysms and dissection often occur in atheromatous vessels. Specific patterns of disease relevant to the cerebrovascular system are atheromatous and thrombotic carotid occlusion, brain ischemia due to embolus from a proximal source, vessel wall breakage leading to hemorrhage, and rupture of abnormal, thin-walled structures, specifically aneurysms and arteriovenous malformations.

2 hours of symptom onset. This time restriction significantly reduces the number of candidates.

Ischemic Diseases

Anterior Cerebral Artery Stroke. The ACA supplies the medial frontal and parietal lobes, including the motor strip, as it courses into the interhemispheric fissure. ACA stroke results in contralateral leg weakness.

Ischemic stroke accounts for approximately 85% of acute cerebrovascular events. Symptoms of acute ischemic stroke vary based on the functions of the neural tissues supplied by the occluded vessel, and the presence or absence of collateral circulation. The circle of Willis provides extensive collateral circulation, as it connects the right and left carotid arteries to each other and each to the vertebrobasilar system. Patients with complete occlusion of the carotid artery proximal to the circle of Willis may be asymptomatic if the blood flow patterns can shift and provide sufficient circulation to the ipsilateral cerebral hemisphere from the contralateral carotid and the basilar artery. However, the anatomy of the circle of Willis is highly variable. Patients may have a hypoplastic or missing communicating artery, both anterior cerebral arteries supplied by one carotid, or the posterior cerebral artery supplied by the carotid rather than the basilar. Similarly, one vertebral artery is often dominant, and the other hypoplastic. These variations may make disease in a particular vessel more neurologically devastating than in a patient with full collateral circulation. Occlusion distal to the circle of Willis generally results in stroke in the territory supplied by the particular artery. Neurologic deficit from occlusive disease may be temporary or permanent. A patient with sudden-onset focal neurologic deficit that resolves within 24 hours has had a transient ischemic attack (TIA). If the deficit resolves between 24 hours and 1 week, then the patient has had a reversible ischemic neurologic deficit (RIND). A patient with permanent deficits has had a cerebrovascular accident (CVA). CVA is a commonly used, but vague term. Some prefer the term completed stroke.

Thrombotic Disease The most common area of neurologically significant vessel thrombosis is the carotid artery in the neck. Disease occurs at the carotid bifurcation. Thrombosis of a carotid artery chronically narrowed by atheroma can lead to acute carotid occlusion. As discussed above, this may or may not cause symptoms. The more common concern is thromboembolus. Intracranial arterial occlusion by local thrombus formation may occur, but is considered rare compared to embolic occlusion.

Management Complete occlusion of the carotid artery without referable neurologic deficit requires no treatment. A patient with new neurologic deficit and an angiographically demonstrated complete carotid occlusion contralateral to the symptoms should be considered for emergency carotid endarterectomy.11 Surgery should not be performed on obtunded or comatose patients, and should be done within

Embolic Disease Emboli causing strokes may originate in the left atrium due to atrial fibrillation, on a hypokinetic left ventricular wall segment, or in valvular vegetations, an atheromatous aortic arch, or stenosed carotid bifurcations, or from the systemic venous system in the presence of a right-to-left shunt, such as a patent foramen ovale. The majority of emboli enter the anterior (carotid) circulation rather than the posterior (vertebrobasilar) circulation. Characteristic clinical syndromes result from embolic occlusion of the various vessels.

Common Types of Strokes

Middle Cerebral Artery Stroke. The MCA supplies the lateral frontal and parietal lobes and the temporal lobe. MCA stroke results in contralateral face and arm weakness. Dominanthemisphere MCA stroke causes language deficits. Proximal MCA occlusion causing ischemia and swelling in the entire MCA territory can lead to significant intracranial mass effect and midline shift (see Fig. 41-6). Posterior Cerebral Artery Stroke. The PCA supplies the occipital lobe. PCA stroke results in a contralateral homonymous hemianopsia (see Fig. 41-6). Posterior Inferior Cerebellar Artery Stroke. The PICA supplies the lateral medulla and the inferior half of the cerebellar hemispheres. PICA stroke results in nausea, vomiting, nystagmus, dysphagia, ipsilateral Horner’s syndrome, and ipsilateral limb ataxia. The constellation of symptoms resulting from PICA occlusion is referred to as lateral medullary syndrome or Wallenberg’s syndrome. Management Ischemic stroke management has two goals: reopen the occluded vessel and maintain blood flow to borderline ischemic tissues on the border of the vascular territory. This bordering tissue is referred to as the ischemic penumbra. The first goal, reopening the vessel, may be attempted with recombinant tPA.12 tPA administration within 3 hours of the onset of neurologic deficit improves outcome at 3 months. Obtain a head CT immediately in the setting of suspected ischemic stroke to differentiate ischemic from hemorrhagic stroke. Intracranial hemorrhage, major surgery in the previous 2 weeks, gastrointestinal or genitourinary hemorrhage in the previous 3 weeks, platelet count 185 mm Hg are among the contraindications to tPA therapy. The neurology stroke team should be called while taking the patient to head CT. Patients not eligible for tPA require hemodynamic optimization and neurologic monitoring. Admit such patients to the ICU stroke service for blood pressure management and frequent neurologic checks. Allow the blood pressure to run high to maximize cerebral perfusion. SBP more than 180 mm Hg may require treatment. Give normal saline solution without glucose (which could injure neurons in the penumbra), and aim for normovolemia. A stroke patient who worsens clinically should undergo repeat head CT to evaluate for hemorrhage or significant mass effect from swelling. Swelling

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typically peaks 3 to 5 days after the stroke. Significant swelling from an MCA stroke or cerebellar stroke may be life threatening and require hemicraniectomy or suboccipital craniectomy, respectively, as described in the section on neurosurgical emergencies, earlier in this chapter.

Hemorrhagic Diseases Intracranial hemorrhage (ICH) from abnormal or diseased vascular structures accounts for approximately 15% of acute cerebrovascular events. Hypertension and amyloid angiopathy account for most intraparenchymal hemorrhages, although arteriovenous malformations (AVMs), aneurysms, venous thrombosis, tumors, hemorrhagic conversion of ischemic infarct, and fungal infections may also be the cause. The term intracranial hemorrhage is frequently used to mean intraparenchymal hemorrhage, and will be used here. ICH causes local neuronal injury and dysfunction, and can also cause global dysfunction due to mass effect if of sufficient volume. AVM or aneurysm rupture results in subarachnoid hemorrhage (SAH), because the major cerebral and cortical blood vessels travel between the pia and the arachnoid membrane, in the subarachnoid space. SAH can cause immediate concussive-like neuronal dysfunction by exposure of the brain to intra-arterial pressure pulsations during the hemorrhage, and can cause delayed ischemia from cerebral arterial vasospasm. Patients presenting with ICHs that do not follow typical patterns should undergo angiography or MRI to evaluate for possible underlying lesions, such as AVM or tumor. Patients who suffer a hemorrhagic stroke are more likely to present lethargic or obtunded than those who suffer an ischemic stroke. Depressed mental status results from brain shift and herniation secondary to mass effect from the hematoma. Ischemic stroke does not cause mass effect acutely, therefore patients are more likely to present with normal consciousness and a focal neurologic deficit. Hemorrhagic strokes tend to present with a relatively smooth onset of symptoms as the hematoma expands, rather than the immediately maximal symptoms caused by ischemic stroke. Table 41-3 provides a listing of relative incidences of ICH by anatomic distribution.

Hypertension Hypertension increases the relative risk of ICH by approximately fourfold, likely due to chronic degenerative vasculopathy. Hypertensive hemorrhages often present in the basal ganglia, thalamus, or pons, and result from breakage of small perforating arteries that branch off of much larger parent vessels (Fig. 41-15). Most hypertensive hemorrhages should be medically managed. The hematoma often contains intact, salvageable axons because the blood dissects through and along neural tracts, and surgical clot

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evacuation destroys these axons. Factors that indicate that surgery may be appropriate include superficial clot location, young age, nondominant hemisphere, rapid deterioration, and significant mass effect. Most studies fail to show overall improved outcomes. Medical management includes moderate blood pressure control, normalizing platelet and clotting function, phenytoin, and electrolyte management. Intubate patients who cannot clearly follow commands, to prevent aspiration and hypercarbia. Follow and document the neurologic exam and communicate with the family regarding appropriateness for rehabilitation versus withdrawal of care.

Amyloid Angiopathy The presence of pathologic amyloid deposition in the media of small cortical vessels compromises vessel integrity, predisposes to more superficial (lobar) hemorrhages, and may cause multiple hemorrhages over time. The superficial location of amyloid hemorrhages may make surgical evacuation less morbid than for typical deep hypertensive hemorrhages. Approach medical management and family counseling similarly to patients with hypertensive hemorrhages.

Cerebral Aneurysm An aneurysm is focal dilatation of the vessel wall, and is most often a balloon-like outpouching, but may also be fusiform. Aneurysms usually occur at branch points of major vessels [e.g., internal carotid artery (ICA) bifurcation], or at the origin of smaller vessels (e.g., posterior communicating artery or ophthalmic artery). Approximately 85% of aneurysms arise from the anterior circulation (carotid) and 15% from the posterior circulation (vertebrobasilar). Table 41-4 shows the percentage distribution of cerebral aneurysms by location. Aneurysms are thin-walled and at risk for rupture. The major cerebral vessels, and therefore aneurysms, lie in the subarachnoid space. Rupture results in SAH. The aneurysmal tear may be small and seal quickly or not. SAH may consist of a thin layer of blood in the CSF spaces, or thick layers of blood around the brain and extending into brain parenchyma, resulting in a clot with mass effect. The meningeal linings of the brain are sensitive, so SAH usually results in a sudden, severe “thunderclap” headache. A patient will classically describe “the worst headache of my life.” Presenting neurologic symptoms may range from mild headache to coma to sudden death. The Hunt-Hess grading system categorizes patients clinically (Table 41-5). Patients with symptoms suspicious for SAH should have a head CT immediately. Acute SAH appears as a bright signal in the fissures and CSF cisterns around the base of the brain, as shown in Fig. 41-16. CT is rapid, noninvasive, and approximately 95% sensitive. Patients with suspicious symptoms but negative head CT should

Table 41-3 Anatomic Distribution of Intracranial Hemorrhages (ICHs) and Correlated Symptoms % of ICHs

Location

Classic Symptoms

50%

Contralateral hemiparesis

15% 10–20%

Basal ganglia (putamen, globus pallidus), internal capsule Thalamus Cerebral white matter (lobar)

10–15% 10%

Pons Cerebellum

1–6%

Brain stem (excluding pons)

Contralateral hemisensory loss Depends on location (weakness, numbness, partial loss of visual field) Hemiparesis; may be devastating Lethargy or coma due to brain stem compression and/or hydrocephalus Often devastating

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A

B

FIG. 41-15. A . Head CT scan of a patient with left-sided weakness and progressive lethargy reveals a right basal ganglia hemorrhage. The blood clot is bright white. Hypodensity around the clot represents cerebral edema. There is blood within the ventricular system. B . Another patient with intraventricular extension of a basal ganglia hemorrhage. The patient developed right-sided weakness and then lethargy. Head CT indicated hydrocephalus. A ventriculostomy was placed for CSF drainage (arrowhead indicates cross-sectional view of the catheter entering the anterior horn of the right lateral ventricle).

undergo lumbar puncture. A lumbar puncture (LP) with xanthochromia and high red blood cell (RBC) counts (usually 100,000/mL), which do not decrease between tubes 1 and 4, is consistent with SAH. Negative CT and LP essentially rules out SAH. Patients diagnosed with SAH require four-vessel cerebral angiography within 24 hours to assess for aneurysm or other vascular malformation. Catheter angiography remains the gold standard for assessing the patient’s cerebral vasculature, relevant anomalies, and presence, location, and morphology of the cerebral aneurysms. Parts A and B of Fig. 41-17 demonstrate the typical digital subtraction angiographic (DSA) view of a cerebral aneurysm. Part C shows the anatomy of Table 41-4 Prevalence of Cerebral Aneurysm by Location Prevalence (%)

Aneurysm Location (Vernacular Name)

Anterior circulation 85%

30% Anterior communicating artery (A-Comm) 25% Posterior communicating artery (P-Comm) 20% Middle cerebral artery bifurcation (MCA) 10% Other

Posterior circulation 15%

10% Basilar artery, most frequently at the basilar tip 5% Vertebral artery, usually at the posterior inferior cerebellar artery (PICA)

the circle of Willis in a simplified graphic representation to assist in visualizing the locations of various cerebral aneurysms. SAH patients should be admitted to the neurologic ICU. HuntHess grade 4 and 5 patients require intubation and hemodynamic monitoring and stabilization. The current standard of care for ruptured aneurysms requires early aneurysmal occlusion. There are two options for occlusion. The patient may undergo craniotomy with microsurgical dissection and placement of a titanium clip across Table 41-5 The Hunt-Hess Clinical Grading System for Subarachnoid Hemorrhage Hunt-Hess Grade

Clinical Presentation

0 1

Asymptomatic; unruptured aneurysm Awake; asymptomatic or mild headache; mild nuchal rigidity Awake; moderate to severe headache, cranial nerve palsy (e.g., CN III or IV), nuchal rigidity Lethargic; mild focal neurologic deficit (e.g., pronator drift) Stuporous; significant neurologic deficit (e.g., hemiplegia) Comatose; posturing

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options for treating symptomatic vasospasm are intra-arterial papaverine and balloon angioplasty. Aneurysmal SAH has an approximate mortality rate of 50% in the first month. Approximately one-third of survivors returns to preSAH function, and the remaining two-thirds have mild to severe disability. Most require rehabilitation after hospitalization.

Arteriovenous Malformations

FIG. 41-16. Head CT scan of a patient who experienced a sudden, severe headache. Subarachnoid hemorrhage is visible as hyperdense signal in the interhemispheric fissure (number 1), bilateral sylvian fissures (number 2 shows the left fissure), and in the ambient cisterns around the midbrain (number 3). This gives the classic five-pointed-star appearance of SAH. Visible temporal tips of the lateral ventricles indicate hydrocephalus.

the aneurysm neck to exclude the aneurysm from the circulation and reconstitute the lumen of the parent vessel. The second option is to take the patient to the interventional neuroradiology suite for endovascular placement of looped titanium coils inside the aneurysm dome. The coils support thrombosis and prevent blood flow into the aneurysm. Factors favoring craniotomy and clipping include young age, good medical condition, and broad aneurysm necks. Factors favoring coiling include old or medically-frail patients and narrow aneurysm necks. Clipping results in a more definitive cure, because coils can move and compact over time, requiring repeat angiograms and placement of additional coils. The decision to clip or coil is complex and should be fully explored. The International Subarachnoid Aneurysm Trial (ISAT) researchers suggested that endovascular occlusion resulted in better outcomes for certain types of cerebral aneurysms, although this trial was marred by poor selection and randomization techniques, and the validity of its conclusions have been questioned.13 Debate also continues regarding optimal care for unruptured intracranial aneurysms.14 SAH patients often require 1 to 3 weeks of ICU care after aneurysm occlusion for medical complications that accompany neurologic injury. In addition to routine ICU concerns, SAH patients are also at risk for cerebral vasospasm. In vasospasm, cerebral arteries constrict pathologically and can cause ischemia or stroke from 4 to 21 days after SAH. Current vasospasm prophylaxis includes maintaining hypertension and mild hypervolemia to optimize perfusion, and administering nimodipine, a calcium channel blocker that may decrease the incidence and degree of spasm. Neurointerventional

AVMs are abnormal, dilated arteries and veins without an intervening capillary bed. The nidus of the AVM contains a tangled mass of vessels, but no neural tissue. AVMs may be asymptomatic or present with SAH or seizures. Small AVMs present with hemorrhage more often than large AVMs, which tend to present with seizures. Headache, bruit, or focal neurologic deficits are less common symptoms. AVMs hemorrhage at an average rate of 2 to 4% a year. Figure 41-18 demonstrates the angiographic appearance of an AVM in arterial and venous phases. There are several management differences for SAH due to AVM versus aneurysm. Definitive therapy for the AVM is usually delayed 3 to 4 weeks to allow the brain to recover from acute injury. There is less risk of devastating early rebleeding from AVMs, and vasospasm is less relevant. Adjacent brain may be hyperemic after removal of the high-flow arteriovenous (A-V) shunt, so hypertension and hypervolemia are not beneficial. Three therapeutic modalities for AVMs are currently in common use: microsurgical excision, endovascular glue embolization, and stereotactic radiosurgery. AVMs that are large, near eloquent cortex, or that drain to deep venous structures are considered high grade and more difficult to surgically resect without causing significant neurologic deficit. Radiosurgery can treat these lesions, although it is limited to lesions less than 3 cm in diameter and has a 2-year lag time (i.e., the AVM may bleed in the interval). Embolization reduces flow through the AVM. It is usually considered adjunctive therapy, but may rarely be the sole treatment for deep, inaccessible lesions.

TUMORS OF THE CENTRAL NERVOUS SYSTEM A wide variety of tumors affect the brain and spine. Primary benign and malignant tumors arise from the various elements of the CNS, including neurons, glia, and meninges. Tumors metastasize to the CNS from many primary sources. Presentation varies widely depending on relevant neuroanatomy. Prognosis depends on histology and anatomy. Modern brain tumor centers utilize team approaches to CNS tumors, as patients may require a combination of surgery, radiation therapy, chemotherapy, stereotactic radiosurgery, and research protocol enrollment. Tumors affecting the peripheral nervous system are discussed in the peripheral nerve section.

Intracranial Tumors Intracranial tumors are brain tumors that cause mass effect, dysfunction or destruction of adjacent neural structures, swelling, abnormal electrical activity, or a combination of these. Supratentorial tumors commonly present with focal neurologic deficit, such as contralateral limb weakness or visual field deficit, or headache or seizure. Infratentorial tumors often cause increased ICP, due to hydrocephalus due to compression of the fourth ventricle, leading to headache, nausea, vomiting, or diplopia. Cerebellar hemisphere or brain stem dysfunction can lead to ataxia, nystagmus, or cranial nerve palsies. Infratentorial tumors rarely cause seizures. All patients with symptoms concerning for brain tumor should undergo MRI with and without gadolinium. Initial management of a

A

B

C FIG. 41-17. A . Anteroposterior view after injection of contrast dye in the left internal carotid artery demonstrates a 13-mm diameter anterior communicating artery aneurysm (labeled A Comm). The left internal carotid, middle carotid, and anterior cerebral arteries are clearly seen. B . Lateral view of the same injection again demonstrates the aneurysm. C . Figure depicting the anatomy of the circle of Willis in relation to key structures on the base of the brain. ACoA = anterior communicating artery; A1 = first section of anterior cerebral artery (ACA), before ACoA; A2 = second section of ACA, after ACoA; BA = basilar artery; CN III = third cranial nerve (oculomotor nerve); CN IV = fourth cranial nerve (trochlear nerve); I = infundibulum (the attachment of the pituitary stalk); ICA = internal cerebral artery; MCA = middle cerebral artery; OA = ophthalmic artery; ON = optic nerve; PCoA = posterior communicating artery; P1 = first section of posterior cerebral artery (PCA), before the PCoA; P2 = second section of the PCA, after the PCoA; SCA = superior cerebellar artery. (Reproduced with permission from Diagnostic Cerebral Angiography, Osborn.)

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B FIG. 41-18. A . Lateral view after injection of contrast dye in the left internal carotid artery demonstrates a 3 × 4 cm left frontal arteriovenous malformation indicated by arrowheads. This image was taken 1.06 seconds after dye injection, and is referred to as an arterial phase image. B . Same view taken 4.10 seconds after dye injection, providing a venous phase image. The arrow points to the AVM nidus. The arrowheads indicate two pathologically enlarged draining veins.

patient with a symptomatic brain tumor generally includes dexamethasone (if edema is present) and phenytoin (supratentorial tumors only). Patients with significant weakness, lethargy, or hydrocephalus should be admitted for observation until definitive care is administered.

Glial Tumors Glial cells provide the anatomic and physiologic support for neurons and their processes in the brain. The several types of glial cells give rise to distinct primary CNS neoplasms.

Astrocytomas Metastatic Tumors Prolonged cancer patient survival and improved CNS imaging have increased the likelihood of diagnosing cerebral metastases. The sources of most cerebral metastases are (in decreasing frequency) the lung, breast, kidney, GI tract, and melanoma. Lung and breast cancers account for more than half of cerebral metastases. Metastatic cells usually travel to the brain hematogenously and frequently seed the gray-white junction. Other common locations are the cerebellum and the meninges. The latter leads to carcinomatous meningitis, also known as leptomeningeal carcinomatosis. MRI pre– and post– contrast administration is the study of choice for evaluation. Figure 41-19 demonstrates bilateral cerebellar metastases. Metastases are often very well circumscribed, round, and multiple. Such findings should instigate a metastatic work-up, including CT scan of the chest, abdomen, and pelvis, and a bone scan. Management depends on the primary tumor, tumor burden, patient’s medical condition, and location and number of metastases. The patient’s and family’s beliefs regarding aggressive care must be considered. Craniotomy may benefit patients with one or two accessible metastases and should be discussed. Studies do not support craniotomy unless all detectable metastases can be resected. Surgery should be followed by whole brain radiation therapy. Surgery plus radiation therapy increases average survival from 1 month to 8 months. Recent data suggest stereotactic radiosurgery (e.g., gamma knife) may be applied to multiple metastases in one session with improved outcome.

Astrocytoma is the most common primary CNS neoplasm. The term glioma is often used to refer to astrocytomas specifically, excluding other glial tumors. Astrocytomas are graded from I to IV. Grades I and II are referred to as low-grade astrocytoma, grade III as anaplastic astrocytoma, and grade IV as glioblastoma multiforme (GBM). Prognosis varies significantly between grades I/II, III, and IV, but not between I and II. Median survival is 8 years after diagnosis with a low-grade tumor, 2 to 3 years with an anaplastic astrocytoma, and roughly 1 year with a GBM. GBMs account for almost two-thirds of all astrocytomas, anaplastic astrocytomas account for two-thirds of the rest, and low-grade astrocytomas the remainder. Figure 41-20 demonstrates the typical appearance of a GBM. The great majority of astrocytomas infiltrate adjacent brain. Juvenile pilocytic astrocytomas and pleomorphic xanthoastrocytoma are exceptions. These are circumscribed, low grade, and associated with good prognosis. Histologic features associated with higher grade include hypercellularity, nuclear atypia, and endovascular hyperplasia. Necrosis is present only with GBMs; it is required for the diagnosis. Gross total resection should be attempted for suspected astrocytomas. Motor cortex, language centers, deep or midline structures, or brain stem location may make this impossible without unacceptable, devastating neurologic deficit. These may require stereotactic needle biopsy. Gross total resection followed by radiation therapy improves survival for all grades, although radiation therapy may be delayed

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A

B

FIG. 41-19. A . Precontrast T1-weighted axial MRI demonstrating bilateral hemorrhagic cerebellar metastases. Patient presented with ataxia and then lethargy progressing to deep coma. This patient has total effacement of the fourth ventricle and severe brain stem compression. The fourth ventricle CSF space should be at the tip of the arrowhead. Patient recovered to normal mental status after emergent posterior fossa craniotomy. B . Postcontrast T1-weighted axial MRI demonstrating a ring-enhancing lesion in the lateral left temporal lobe with moderate edema. The uncus (U) is compressing the left cerebral peduncle (CP) and displacing the brain stem to the right.

until recurrence in low-grade tumors. Chemotherapy may be considered, but is of limited efficacy so far. There are various ongoing research studies for GBM adjuvant therapy; these should be discussed with the patient and family. Other options are carmustine-containing wafers for local chemotherapy (Gliadel) and Iotrex-containing balloons for conformal radiation brachytherapy (Glia-Site), both placed in the resection cavity at the time of surgery. Adjuvant therapy remains marginally effective; survival has changed little over the last several decades.

Oligodendroglioma Oligodendroglioma accounts for approximately 10% of gliomas. They often present with seizures. Calcifications and hemorrhage on CT or MRI suggest the diagnosis. Oligodendrogliomas are also graded from I to IV; grade portends prognosis. Prognosis is better overall than for astrocytomas. Median survival ranges from 2 to 7 years for highest and lowest grade tumors, respectively. Aggressive resection improves survival. Many oligodendrogliomas will respond to procarbazine, lomustine (CCNU), vincristine (PCV) chemotherapy. Radiation has not been clearly shown to prolong survival.

Ependymoma The lining of the ventricular system consists of cuboidal/ columnar ependymal cells from which ependymomas may arise. Two-thirds of adult ependymomas are infratentorial, while most

pediatric ependymomas are supratentorial. Supratentorial ependymomas arise from the lateral or third ventricles. The infratentorial tumors arise from the floor of the fourth ventricle (i.e., off the back of the brain stem). The most common symptoms are headache, nausea, vomiting, or vertigo, secondary to increased ICP from obstruction of CSF flow through the fourth ventricle. The tumors may grow out the foramina of Luschka to form a cerebellopontine angle (CPA) mass, or may spread through the CSF to form “drop mets” in the spinal cord. Two main histologic subtypes are papillary ependymomas and anaplastic ependymomas, the latter characterized by increased mitotic activity and areas of necrosis. Gross total resection is often impossible because the tumor arises from the brain stem. The goal of surgery is maximal resection without injuring the very delicate brain stem. Suboccipital craniotomy and midline separation of the cerebellar hemispheres allows access to tumors in the fourth ventricle. Postoperative radiation therapy significantly improves survival. Patients with CSF spread documented by lumbar puncture or contrast MRI should also have whole-spine radiation plus focused doses to visualized metastases.

Choroid Plexus Papilloma The choroid plexus is composed of many small vascular tufts covered with cuboidal epithelium. It represents part of the interface between blood and brain. The choroid cells create CSF from blood and release it into the ventricular system. Choroid plexus papillomas

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B FIG. 41-20. A . Postcontrast T1-weighted axial MRI demonstrating a ring-enhancing lesion in the anteromedial right temporal lobe with central necrosis (dark area) consistent with glioblastoma multiforme. B . T2-weighted axial MRI with extensive bright signal signifying peritumoral edema seen with GBMs.

and choroid plexus carcinomas (rare, mostly pediatric) may arise from these cells. Papillomas usually occur in infants (usually supratentorial in the lateral ventricle), but also occur in adults (usually infratentorial in the fourth ventricle). Papillomas are well circumscribed and vividly enhance due to extensive vasculature. Like ependymomas, adult choroid plexus papillomas usually present with symptoms of increased ICP. Treatment is surgical excision. Total surgical excision is curative; recurrent papillomas should be re-resected. Do not use radiation or chemotherapy for papillomas. Radiation is adjunctive to aggressive surgery for carcinomas, but results are poor regardless.

Neural Tumors and Mixed Tumors Neural and mixed tumors are a diverse group that includes tumors variously containing normal or abnormal neurons and/or normal or abnormal glial cells. Primitive neuroectodermal tumors (PNETs) arise from bipotential cells, capable of differentiating into neurons or glial cells.

Medulloblastoma PNETs are the most common medulloblastomas. Most occur in the first decade of life, but there is a second peak around age 30. Medulloblastoma is the most common malignant pediatric brain tumor. They are usually midline. Most occur in the cerebellum and present with symptoms of increased ICP. Histologic characteristics include densely packed small round cells with large nuclei and scant cytoplasm. They are generally not encapsulated, frequently

disseminate within the CNS, and should undergo surgical resection followed by radiation therapy and chemotherapy.

Ganglioglioma Ganglioglioma is a mixed tumor in which both neurons and glial cells are neoplastic. They occur in the first three decades of life, often in the medial temporal lobe, as circumscribed masses that may contain cysts or calcium and may enhance. The presenting symptom is usually a seizure, due to the medial temporal location. Patients have a good prognosis after complete surgical resection.

Neural Crest Tumors Multipotent neural crest cells develop into a variety of disparate cell types, including smooth muscle cells, sympathetic and parasympathetic neurons, melanocytes, Schwann cells, and arachnoid cap cells. They migrate in early development from the primitive neural tube throughout the body.

Miscellaneous Tumors Meningioma Meningiomas are derived from arachnoid cap cells of the arachnoid mater. They appear to arise from the dura mater grossly and on MRI, and so are commonly referred to as dural-based tumors. The most common intracranial locations are along the falx (Fig. 41-21), the convexities (i.e., over the cerebral hemispheres), and the sphenoid wing. Less common locations include the foramen

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or linear accelerator technology). The main complication with treatment is damage to the facial nerve (cranial nerve VII), which runs through the internal auditory canal with the vestibulocochlear nerve. Risk of facial nerve dysfunction increases with increasing tumor diameter.

Pituitary Adenoma

FIG. 41-21. Postcontrast T1-weighted coronal MRI demonstrating a brightly enhancing lesion arising from the falx cerebri with moderate edema and mass effect on the right lateral ventricle. This is a falcine meningioma. Note also the small separate meningioma arising from the dura over the cerebral convexity.

magnum, olfactory groove, and inside the lateral ventricle. Most are slow growing, encapsulated, benign tumors. Aggressive atypical or malignant meningiomas may invade adjacent bone or into the cortex. Previous cranial irradiation increases the incidence of meningiomas. Approximately 10% of patients with a meningioma have multiple meningiomas. Total resection is curative, although involvement with small perforating arteries or cranial nerves may make total resection of skull base tumors impossible without significant neurologic deficit. Small, asymptomatic meningiomas can be followed until symptomatic or significant growth is documented on serial imaging studies. Atypical and malignant meningiomas may require postoperative radiation. Patients may develop recurrences from the surgical bed or distant de novo tumors.

Vestibular Schwannoma (Acoustic Neuroma) Vestibular schwannomas arise from the superior half of the vestibular portion of the vestibulocochlear nerve (cranial nerve VIII) (Fig. 41-22). They most commonly present with progressive hearing loss, tinnitus, or balance difficulty. Large tumors may cause brain stem compression and obstructive hydrocephalus. Bilateral acoustic neuromas are pathognomonic for neurofibromatosis type 2, a syndrome resulting from chromosome 22 mutation. NF-2 patients have an increased incidence of spinal and cranial meningiomas and gliomas. Vestibular schwannomas may be treated with microsurgical resection or with conformal stereotactic radiosurgery (gamma knife

Pituitary ademomas arise from the anterior pituitary gland (the adenohypophysis). Tumors less than 1 cm diameter are microadenomas; larger tumors are macroadenomas. Pituitary tumors may be functional (i.e., secrete endocrinologically active compounds at pathologic levels) or nonfunctional (i.e., secrete nothing or inactive compounds). Functional tumors are often diagnosed when quite small, due to endocrine dysfunction. The most common endocrine syndromes are Cushing’s disease due to adrenocorticotropic hormone (ACTH) secretion, Forbes-Albright syndrome due to prolactin secretion, and acromegaly due to growth hormone secretion. Nonfunctional tumors commonly present when larger due to mass effect. Figure 41-23 demonstrates a large pituitary adenoma. Common symptoms include visual field deficits due to compression of the optic chiasm, or panhypopituitarism due to compression of the gland. Hemorrhage into a pituitary tumor causes abrupt symptoms of headache, visual disturbance, decreased mental status, and endocrine dysfunction. This is known as pituitary apoplexy. Pituitary tumors should be decompressed surgically to eliminate symptomatic mass effect and/or to attempt endocrine cure. Prolactinomas usually shrink with dopaminergic therapy. Consider surgery for prolactinomas with persistent mass effect or endocrinologic dysfunction in spite of adequate dopamine agonist therapy. Most pituitary tumors are approached through the nose by the transsphenoidal approach. Endoscopic sinus surgery techniques may be helpful and are increasingly being used.

Hemangioblastoma Hemangioblastomas occur almost exclusively in the posterior fossa. Twenty percent occur in patients with von Hippel-Lindau (VHL) disease, a multisystem neoplastic disorder. Other tumors associated with VHL are renal cell carcinoma, pheochromocytoma, and retinal angiomas. Many appear as cystic tumors with an enhancing tumor on the cyst wall known as the mural nodule. Surgical resection is curative for sporadic (non-VHL associated) tumors. Pathology reveals abundant thin-walled vascular channels, so internal debulking may be bloody. En bloc resection of the mural nodule alone, leaving the cyst wall, is sufficient.

Lymphoma CNS lymphoma may arise primarily in the CNS or secondary to systemic disease. Recent increasing incidence may be due to increasing numbers of immunocompromised people in the transplant and AIDS populations. Presenting symptoms include mental status changes, headache due to increased ICP, and cranial nerve palsy due to lymphomatous meningitis (analogous to carcinomatous meningitis). Many are hyperdense on CT scan due to their dense cellularity, and most enhance. Surgical excision has little role. Diagnosis is often made by stereotactic needle biopsy. Subsequent treatment includes steroids, whole brain radiation, and chemotherapy. Intrathecal methotrexate chemotherapy is an option.

Embryologic Tumors Embryologic tumors result from embryonal remnants that fail to involute completely or differentiate properly during development.

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B FIG. 41-22. A . Postcontrast T1-weighted axial MRI demonstrating a brightly enhancing mass on the right vestibular nerve with an enhancing tail going into the internal auditory canal (arrowhead). Pathology demonstrated vestibular schwannoma. B . Postcontrast T1-weighted sagittal MRI of the same lesion, indicated by the arrowhead. Note small incidental meningioma at the top of the scan.

Craniopharyngioma Craniopharyngiomas are benign cystic lesions that occur most frequently in children. There is a second peak of occurrence around 50 years of age. All pediatric, and half of adult craniopharyngiomas calcify. Symptoms result from compression of adjacent structures, especially the optic chiasm. Pituitary or hypothalamic dysfunction or hydrocephalus may develop. Treatment is primarily surgical. Excision is easier in children, as the tumor is usually soft and suckable. Adult tumors are often firm and adherent to adjacent vital structures. Visual loss, pituitary endocrine hypofunction, diabetes insipidus, and cognitive impairment from basal frontal injury may result from incautious resection.

Epidermoid These are cystic lesions with stratified squamous epithelial walls from trapped ectodermal cell rests that grow slowly and linearly by desquamation into the cyst cavity. The cysts contain keratin, cholesterol, and cellular debris (Fig. 41-24). They occur most frequently in the cerebellopontine angle and may cause symptoms due to brain stem compression. Recurrent bouts of aseptic meningitis may occur due to release of irritating cyst contents into the subarachnoid space (Mollaret’s meningitis). Treatment is surgical drainage and removal of cyst wall. Intraoperative spillage of cyst contents leads to severe chemical meningitis and must be avoided by containment and aspiration.

Dermoid Dermoids are less common than epidermoids. They contain hair follicles and sebaceous glands in addition to a squamous epithelium.

Dermoids are more commonly midline structures and are associated with other anomalies than are epidermoids. They may be traumatic, as from a lumbar puncture that drags skin structures into the CNS. Bacterial meningitis may occur when associated with a dermal sinus tract to the skin. Treatment of symptomatic lesions is surgical resection, again with care to control cyst contents.

Teratoma Teratomas are germ cell tumors that arise in the midline, often in the pineal region (the area behind the third ventricle, above the midbrain and cerebellum). They contain elements from all three embryonal layers: ectoderm, mesoderm, and endoderm. Teratomas may contain skin, cartilage, GI glands, and teeth. Teratomas with more primitive features are more malignant, while those with more differentiated tissues are more benign. Surgical excision may be attempted. Prognosis for malignant teratoma is very poor.

Spinal Tumors A wide variety of tumors affect the spine. Approximately 20% of CNS tumors occur in the spine. The majority of spinal tumors are histologically benign, unlike cranial tumors. Understanding the two major spinal concepts facilitates understanding of the effects of spinal tumors. The two concepts are spinal stability and neural compression. Destruction of bones or ligaments can cause spinal instability, and lead to deformities such as kyphosis or subluxation and possible subsequent neural compression. Tumor growth in the spinal canal or neural foramina can cause direct compression of the spinal cord or nerve roots and cause loss of function. Anatomic categorization provides the most logical approach to these tumors. The various tumors present in characteristic locations. An understanding

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FIG. 41-23. Postcontrast T1-weighted sagittal MRI demonstrating a large sellar/suprasellar lesion involving the third ventricle superiorly, and abutting the midbrain and pons posteriorly. The patient presented with progressive visual field and acuity loss. Pathology and lab work revealed a nonfunctioning pituitary adenoma.

of the anatomy leads to an understanding of the clinical presentation and possible therapeutic options.

Extradural Tumors Extradural tumors comprise 55% of spinal tumors. This category includes tumors arising within the bony structures of the vertebrae and in the epidural space. Destruction of the bone can lead to instability and fractures, leading to pain and/or deformity. Epidural expansion can lead to spinal cord or nerve root compression with radiculopathy or myelopathy, respectively.

Metastatic Tumors. Metastatic tumors are the most common extradural tumors. Spinal metastases most commonly occur in the thoracic and lumbar vertebral bodies because the greatest volume of red bone marrow is found therein. The most common primary tumors are lymphoma, lung, breast, and prostate. Other sources include renal, colon, thyroid, sarcoma, and melanoma. Most spinal metastases create osteolytic lesions. Osteoblastic, sclerotic lesions suggest prostate cancer in men and breast cancer in women. Patients with progressing neurologic dysfunction or debilitating pain should undergo urgent surgery or radiation therapy. Preoperative neurologic function correlates with postoperative function. Patients may lose function over hours. These patients should be given high-dose intravenous dexamethasone, taken immediately to MRI, and then to the operating room or radiation therapy suite. Indications for surgery

FIG. 41-24. Postcontrast T1-weighted axial MRI demonstrating a nonenhancing mass in the left cerebellopontine angle with brain stem compression. White arrowhead indicates interface of tumor and brain stem. Black arrowhead indicates deformed fourth ventricle. Pathology revealed epidermoid tumor.

include failure of radiation therapy, spinal instability, recurrence after radiation therapy, and the need for diagnosis in cases of unknown primary tumors. Most cases with significant bone involvement require both decompression and fusion. Bony fusion usually takes 2 to 3 months. Prognosis governs operative decisions. Surgery is unlikely to improve quality of life for patients with a life expectancy of 3 months or less, but is likely to improve quality of life for patients with life expectancy of 6 months or more. Benefit for patients with 3 to 6 months life expectancy is unclear and requires frank discussion with the patient and family. Patients who are unlikely to tolerate general anesthesia, are already completely paralyzed, or who have very radiosensitive tumors such as myeloma and lymphoma, should generally not be offered surgery.

Primary Tumors. Hemangiomas are benign tumors found in 10% of people at autopsy. They occur in the vertebral bodies of the thoracolumbar spine and are frequently asymptomatic. They are often vascular and may hemorrhage, causing pain or neurologic deficit. Large hemangiomas can destabilize the body and predispose to fracture. Osteoblastic lesions include osteoid osteoma and osteoblastoma. The latter tends to be larger and more destructive. Aneurysmal bone cysts are nonneoplastic, expansile, lytic lesions containing thin-walled blood cavities which usually occur in the lamina or spinous processes of the cervicothoracic spine. They may cause pain or sufficiently weaken the bone to lead to fracture.

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hyperreflexia, spasticity, and gait difficulties. Surgical excision is the treatment of choice. The surgeon often finds a clean margin between the tumor and dura, and between the tumor and spinal cord, allowing en bloc resection without damage to the cord.

Schwannoma. Schwannomas are derived from peripheral nerve sheath Schwann cells. They are benign, encapsulated tumors that almost never undergo malignant degeneration. Two-thirds are entirely intradural, one-sixth are entirely extradural, and one-sixth have the classic dumbbell shape from intradural and extradural components. Symptoms result from radiculopathy, often presenting as pain, or myelopathy. Symptomatic lesions should be surgically resected. The parent nerve root can usually be preserved. Patients with multiple schwannomas likely have neurofibromatosis type 2 (NF-2). Resect symptomatic lesions in NF-2 patients. Neurofibroma. Neurofibromas tend to be more fusiform and grow within the parent nerve, rather than forming an encapsulated mass off the nerve, as with schwannomas. They are benign but not encapsulated. They present similarly to schwannomas and the two may be difficult to differentiate on imaging. Salvage of the parent nerve is more challenging with neurofibromas. Thoracic and high cervical nerve roots may be sacrificed with minimal deficit, to improve likelihood of total resection. Patients with multiple neurofibromas likely have neurofibromatosis type 1, also known as von Recklinghausen’s neurofibromatosis. Resection for symptomatic lesions should be offered. Intramedullary Tumors Intramedullary tumors comprise 5% of spinal tumors. They arise within the parenchyma of the spinal cord. Common presenting symptoms are local or radicular pain, sensory loss, weakness, or sphincter dysfunction. Patients with such symptoms should undergo MRI of the entire spine with and without enhancement.

FIG. 41-25. T2-weighted sagittal MRI of the midthoracic spine demonstrating a well-encapsulated tumor arising from the dura posteriorly and compressing the spinal cord. The patient presented with worsening gait and lower extremity spasticity. Pathology demonstrated meningioma.

Cancers arising primarily in the bony spine include Ewing’s sarcoma, osteosarcoma, chondrosarcoma, and plasmacytoma.

Ependymoma. Ependymomas are the most common intramedullary tumors in adults. There are several histologic variants. The myxopapillary type occurs in the conus medullaris or the filum terminale in the lumbar region and has the best prognosis after resection. The cellular type occurs more frequently in the cervical cord. Many spinal ependymomas have cystic areas and may contain hemorrhage. Surgical removal can improve function. A distinct tumor margin often exists, allowing safer excision. Postoperative radiation therapy after subtotal resection may prolong disease control.

Intradural Extramedullary Tumors Intradural extramedullary tumors comprise 40% of spinal tumors and arise from the meninges or nerve root elements. They may compress the spinal cord, causing myelopathy, or the nerve roots, causing radiculopathy. All of the most common intradural extramedullary tumors are typically benign, slow growing, and well circumscribed. Rare benign epidural masses include arachnoid cysts, dermoids, and epidermoids. Rare malignant epidural tumors include metastases and high-grade gliomas.

Meningioma. Meningiomas arise from the arachnoid mater. They appear to be dural based and enhance on MRI. An enhancing “dural tail” may be seen. They occur most commonly in the thoracic spine (Fig. 41-25), but also arise in the cervical and lumbar regions. Some spinal meningiomas grow into the epidural space. Growth causes cord compression and progressive myelopathy with

Astrocytoma. Astrocytomas are the most common intramedullary tumors in children, although they also occur in adults. They may occur at all levels, although more often in the cervical cord. The tumor may interfere with the CSF-containing central canal of the spinal cord, leading to a dilated central canal, referred to as syringomyelia, or simply syrinx. Spinal astrocytomas are usually low grade, but complete excision is rarely possible due to the nonencapsulated, infiltrative nature of the tumor. As such, patients with astrocytomas fare worse overall than patients with ependymomas. Other Tumors. Other types of rare tumors include high-grade astrocytomas, dermoids, epidermoids, teratomas, hemangiomas, hemangioblastomas, and metastases. Patients usually present with pain. Prognosis depends generally on preoperative function and the histologic characteristics of the lesion.

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SPINE The spine is a complex structure subject to a wide variety of pathologic processes, including degeneration, inflammation, infection, neoplasia, and trauma. Please refer to the sections on trauma, tumor, and infection for discussions of how these processes impact the spine. General concepts relevant to the spine, as well as some common patterns of disease and operative interventions, are presented. The spine consists of a series of stacked vertebrae, intervening discs, and longitudinal ligaments. The vertebrae consist of the vertebral body anteriorly and the pedicles, articular facets, laminae, and spinous processes posteriorly. The intervertebral discs have two components. The tough, fibrous ring that runs around the outer diameter of the two adjacent vertebral bodies is known as the annulus fibrosus. The spongy material inside the ring of the annulus is known as the nucleus pulposus. The annulus and the nucleus provide a cushion between adjacent vertebral bodies, absorb forces transmitted to the spine, and allow some movement between the vertebral bodies. The ligaments stabilize the spine by limiting the motion of adjacent vertebrae. Two concepts critical to understanding the mechanics and pathologic processes affecting the spine are stability and neural compression.

Stability The spinal column is the principal structural component of the axial spine, and it must bear significant loads. The vertebrae increase in size from the top to the bottom of the spine, correlating with the increased total loads the more caudal elements of the spine must bear. The cervical spine is the most mobile. Cervical stability depends greatly on the integrity of the ligaments that run from level to level. The thoracic spine is the least mobile, due to the stabilizing effect of the rib cage. The lumbar spine has relatively massive vertebrae, supports heavy loads, and has intermediate mobility. The sacral spine is fused together and has no intrinsic mobility. The load borne by the lumbar spine is transmitted to the sacrum, and then the pelvis through the sacroiliac joints. The coccyx is the inferiormost segment of the spine and has no significant contribution to load bearing or to mobility. A stable spine is one that can bear normally experienced forces resulting from body mass, movement, and muscle contraction, while maintaining normal structure and alignment. An unstable spine will shift or sublux under these forces. The determinants of spinal stability vary throughout the cervical, thoracic, and lumbar portions. In elementary form, stability depends on the structural integrity of the hard, bony elements of the vertebral column, as well as the tensile integrity and secure attachments of the supporting ligamentous structures. Plain x-rays and CT scans have good sensitivity for detecting bony defects such as fractures or subluxation. MRI better detects disruption of the soft tissues, including ligaments and intervertebral discs. Specific patterns of abnormalities seen on imaging studies may lead to a diagnosis of, or high suspicion of, spinal instability. A common form of nontraumatic spinal instability is lumbar spondylolisthesis (i.e., forward slippage of a lumbar vertebra with relation to the next lower vertebra on which it rests). This results from congenital or degenerative disruption of the pars interarticularis, the critical bridge of bone that spans adjacent facet joints. In the setting of a so-called pars defect, there is no solid bony connection between the adjacent vertebrae. This makes the spine unstable and can lead to slippage. Patients typically present with severe low

FIG. 41-26. Lateral lumbar spine x-ray demonstrates a 25% anterior slippage of L4 on L5 due to a defect in the L4 pars interarticularis. This is called spondylolisthesis.

back pain that is exacerbated with movement and load bearing (mechanical low back pain). Figure 41-26 demonstrates an L4 and L5 spondylolisthesis.

Neural Compression Besides providing a stable central element of the body’s support structure, the spine must also protect the spinal cord as it descends in the central canal, and the nerve roots as they pass from the central canal out the neural foramina to form the peripheral nervous system. In a healthy spine, the spinal cord and nerve roots are suspended in CSF, free of mechanical compression. Pathologic processes that can lead to impingement on the CSF spaces and neural compression include hypertrophic degenerative changes in the intervertebral discs and facet joints, expanding epidural masses such as tumors or abscesses, and slippage of adjacent vertebral bodies with respect to each other (i.e., subluxation). Subluxation may be due to trauma that exceeds the spine’s load-bearing capabilities and leads to structural failure, or chronic structural degradation by degenerative disease, infection, or tumor. Subluxation reduces the cross-sectional area of the central canal and the neural foramina (see Fig. 41-10B). Reduced central canal area can lead to myelopathy. Reduced neural foraminal area can lead to radiculopathy.

Myelopathy Compression of the spinal cord causes disturbance of cord function, known as myelopathy. Myelopathy may be secondary to the direct effects of compression, cord ischemia due to reduced

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Table 41-6 Cervical Disc Herniations and Symptoms by Level Level C4–C5 C5–C6 C6–C7 C7–T1

Frequency

Root Injured

Reflex

Weakness

Numbness

2% 19% 69% 10%

C5 C6 C7 C8

Biceps Triceps

Deltoid Biceps brachii Wrist extensors (wrist drop) Hand intrinsics

Shoulder Thumb Second and third digits Fourth and fifth digits

source: Adapted with permission from Greenberg MS: Handbook of Neurosurgery, 4th ed: Greenberg Graphics, 1997, Chap. 10.2, p 199.

perfusion, or pathologic changes due to repeated cord trauma. These mechanisms lead to demyelination of the corticospinal tracts, which are long descending motor tracts. Corticospinal tract damage leads to upper motor neuron signs and symptoms, including hyperreflexia, spasticity, and weakness. These mechanisms also cause damage to the dorsal columns, which carry ascending proprioception, vibration, and two-point discrimination information. Loss of proprioception makes fine motor tasks and ambulation difficult.

Radiculopathy Compression of the nerve roots causes disturbance of root function, known as radiculopathy. Characteristic features of radiculopathy include lower motor neuron signs and symptoms (hyporeflexia, atrophy, and weakness) and sensory disturbances such as numbness, tingling sensations (paresthesias), burning sensations (dysesthesias), and shooting pain. Myelopathy and radiculopathy often present together in diseases that involve the central canal and the neural foramina. This can lead to lower motor neuron dysfunction at the level of disease, and upper motor neuron dysfunction below that level.

Patterns of Disease Cervical Radiculopathy The cervical nerve roots exit the central canal above the pedicle of the same-numbered vertebra and at the level of the higher adjacent intervertebral disc. So, for example, the C6 nerve root passes above the C6 pedicle at the level of the C5–C6 discs. The cervical nerve roots may be compressed acutely by disc herniation, or chronically by hypertrophic degenerative changes of the discs, facets, and ligaments. Table 41-6 summarizes the effects of various disc herniations. Most patients with acute disc herniations will improve without surgery. Nonsteroidal anti-inflammatory drugs or cervical traction may help alleviate symptoms. Patients whose symptoms do not resolve or who have significant weakness should undergo decompressive surgery. The two main options for nerve root decompression are anterior cervical discectomy and fusion (ACDF) and posterior cervical foraminotomy (keyhole foraminotomy). ACDF allows more direct access to and removal of the pathology (anterior to the nerve root), but requires fusion. Figure 41-27 demonstrates a C6–C7 ACDF. Keyhole foraminotomy allows decompression without requiring fusion, but may be less effective for removing the pathology.

Cervical Spondylotic Myelopathy The term spondylosis refers to diffuse degenerative and hypertrophic changes of the discs, intervertebral joints, and ligaments, that cause spinal stenosis. Spinal cord dysfunction (myelopathy) due to cord compression from cervical spinal degenerative disease is therefore referred to as cervical spondylotic myelopathy, or CSM.

CSM classically presents with spasticity and hyperreflexia due to corticospinal tract dysfunction, upper extremity weakness and atrophy from degeneration of the motor neurons in the anterior horns of the spinal gray matter, and loss of lower extremity proprioception due to dorsal column injury. Figure 41-28 demonstrates typical findings. Patients complain of difficulty buttoning shirts, using utensils, and ambulating. Spondylosis is usually diffuse, so the usual treatment for CSM is multilevel (usually C3–C7) cervical laminectomy, although patients with disease localized over one to three levels may be candidates for anterior decompression and fusion. Figure 41-29 demonstrates the postoperative appearance of a vertebral corpectomy and fusion for CSM. Thorough cervical laminectomy decompresses the cord posteriorly. Patients often have slow recovery due to the extensive chronic changes in the cervical cord, and may benefit from rehabilitation programs. The other disease that classically presents with combined upper and lower motor neuron symptoms is amyotrophic lateral sclerosis (ALS). Care must be taken to avoid offering cervical laminectomy to a patient with undiagnosed ALS. Two findings help differentiate CSM from ALS: cranial nerve dysfunction such as dysphagia (never caused by cervical spine disease) and sensory disturbance (not found in ALS).

Thoracic Disc Herniation Thoracic disc herniation accounts for less than 1% of herniated discs. They may present with radicular pain or sensory or motor changes in the lower extremities, due to cord compression. A posterior approach via midline incision and laminectomy should be avoided because of the high incidence of cord injury from manipulation and retraction. Anterior approaches via thoracotomy minimize risk to the cord and allow excellent access to the disc. The radicular arteries running from the aorta to the thoracic cord should be spared when possible, to avoid ischemia.

Lumbar Radiculopathy Lumbar nerve roots exit the thecal sac, pass over the higher adjacent disc space, and exit the canal under the pedicle of the samenumbered vertebra. Therefore, the L5 nerve root passes over the L4–L5 disc space and exits under the L5 pedicle (Fig. 41-30). Lumbar discs may herniate with or without a history of trauma or straining. They normally cause pain lancing down the leg (Table 41-7). Most acute herniated lumbar discs improve symptomatically without surgery. Surgery is indicated for symptoms persisting more than 6 to 8 weeks, progressive motor deficit (e.g., foot drop), or for patients with incapacitating pain not manageable with analgesics. Discectomy is performed using a midline incision, partial removal of the overlying laminae (hemilaminectomy or laminotomy), identification of the thecal sac and nerve root, and extraction of disc fragments. Free-floating disc fragments may be found. Often, however, the herniated disc material is still contained within the annulus, and so the annulus must be incised and the disc space curetted.

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A

B

FIG. 41-27. A . Anteroposterior cervical spine x-ray showing the position of an anterior cervical plate used for stabilization after C6–C7 discectomy. Patient presented with right triceps weakness and dysesthesias in the right fifth digit. MRI revealed a right paracentral C6–C7 herniated disc compressing the exiting C7 nerve root. B . Lateral cervical spine x-ray of the same patient clearly demonstrates the position of the plate and screws. The allograft bone spacer placed in the drilled-out disc space is also apparent.

After lumbar discectomy, approximately two-thirds of patients will have complete relief of pain, and up to 85% will have significant improvement.

Neurogenic Claudication Neurogenic claudication is characterized by low back and leg pain that occurs while walking and is relieved by stopping, leaning forward, or sitting. It is normally caused by degenerative lumbar stenosis causing compression of the cauda equina. Neurogenic claudication must be distinguished from vascular claudication. Vascular claudication pain tends to resolve quickly with cessation of walking without need to change position, be in a stocking distribution rather than a dermatomal distribution, and be associated with cold, pale feet. Patients typically have a normal neurologic exam. Patients with neurogenic claudication have a slowly progressive course and may be surgical candidates when their pain interferes with their lifestyle. The usual surgery is an L3 to L5 lumbar laminectomy to decompress the nerve roots.

Cauda Equina Syndrome Cauda equina syndrome is due to compression of the cauda equina and may result from massive disc herniation, epidural hematoma, epidural abscess, tumor, or subluxation from trauma. Patients with cauda equina compression often present with urinary

retention, saddle anesthesia, or progressing leg weakness. Saddle anesthesia is numbness in the perineum, genitals, buttocks, and upper inner thighs. Patients with suspected cauda equina syndrome should undergo immediate MRI of the lumbar spine to evaluate for a surgical lesion. Mass lesions should be removed urgently via laminectomy to preserve sphincter function and ambulation.

Spine Fusion Surgery Patients whose spines have been destabilized by disease or by surgical intervention require fusion to restore stability. Fusion procedures lock adjacent vertebrae together. Fusion occurs when the body forms a solid mass of bone incorporating the adjacent vertebrae, eliminating normal intervertebral movement. Stabilization and immobilization promote bony fusion. Internal instrumentation and external orthoses are often used to stabilize and immobilize the spinal segment being fused.

Spinal Instrumentation Internal fixation devices for spinal segmental immobilization have been developed for all levels of the spine. Most spinal instrumentation constructs have two elements. The first element is a device that solidly attaches to the vertebral bodies. Options include wires wrapped around laminae or spinous processes, hooks placed under the lamina or around the pedicles, or screws placed in the pedicles or

FIG. 41-29. Lateral cervical spine x-ray status post C5 corpectomy for CSM. This involves removal of the C4–C5 disc, C5 vertebral body, and C5–C6 disc, decompressing at two levels. A bone strut is visible bridging C4 to C6. The plate and screws stabilize the segments.

FIG. 41-28. T2-weighted sagittal MRI of the cervical spine showing multilevel degenerative changes causing spinal stenosis that is worst at C5–C6. Note the bright signal within the cord at that level, consistent with myelopathy.

A

B

FIG. 41-30. A . T2-weighted sagittal MRI shows an L5–S1 disc herniation causing significant canal compromise and displacement of nerve roots. B . T2-weighted axial MRI of the same patient shows the large left paracentral disc herniation at L5–S1. Arrowheads delineate the extent of the herniation. The arrow indicates the right S1 nerve root passing through free of compression. The left S1 nerve root is under severe compression and is not seen.

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Table 41-7 Lumbar Disc Herniations and Symptoms by Level Level

Frequency

Root Injured

Reflex

Weakness

Numbness

L3–L4 L4–L5 L5–S1

5% 45% 50%

L4 L5 S1

Patellar

Quadriceps Tibialis anterior (foot drop) Gastrocnemius

Anterior thigh Great toe Lateral foot

Achilles

source: Adapted with permission from Greenberg MS: Handbook of Neurosurgery, 4th ed: Greenberg Graphics, 1997, Chap. 10.2, p 183.

the vertebral bodies. The second element is a device that traverses vertebral segments. Options include rods and plates that lock directly to the wires, hooks, or screws at each vertebral level. Spinal instrumentation devices are available for anterior and posterior fusion in the cervical, thoracic, and lumbar regions. Most modern spinal instrumentation devices are made of titanium to minimize problems with future MRI scanning (Fig. 41-31). All spinal instrumentation constructs will eventually fail by loosening or breaking if bony fusion does not occur.

Arthrodesis Arthrodesis refers to the obliteration of motion or instability by incorporating the relevant components into a solid mass of bone.

A

Arthrodesis must occur in any fused segment to have long-term stability. Failure of arthrodesis results in failed fusion, often in the form of a fibrous nonunion. The rates of successful fusion are higher in the cervical spine than the lumbar spine. Arthrodesis requires ingrowth of new bone formed by the patient’s osteoblasts across the unstable defect. Inserting graft material, such as autograft or allograft, into the defect provides a bridge for osteoblasts and promotes fusion. The term autograft refers to the patient’s own bone, often harvested from the iliac crest. Iliac crest bone graft is a source of both cortical and cancellous bone. Cortical bone provides structural support, while cancellous bone provides a matrix for bony ingrowth. The term allograft refers to sterilized bone from human tissue banks. Allografts also may be cortical, cancellous, or both.

B

FIG. 41-31. A . Lateral lumbar spine x-ray showing pedicle screws and connecting rods used to stabilize L4 with respect to L5. This instrumentation was placed as part of a fusion operation to stabilize progressive L4–L5 spondylolisthesis with intractable low back pain. B . Anteroposterior lumbar spine x-ray showing L3 to L5 instrumentation with pedicle screws and connecting rods. The patient had previously sustained an L4 burst fracture. Note the significant loss of height of the L4 body compared to adjacent levels. The small row of staples to the right delineates the incision over the iliac crest used to harvest cancellous bone as a nonstructural osteoinductive autograft fusion designed to induce formation of a solid bone bridge from L3 to L5 (arthrodesis).

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Allograft lacks the array of osteoinductive endogenous compounds intrinsic to autograft, although supplemental products such as demineralized bone matrix paste can be added to encourage new bone formation. Other techniques for increasing the rates of successful fusion are being developed, including the integration of osteoinductive bone morphogenetic proteins, known as BMPs, into the fusion constructs.

PERIPHERAL NERVE Common pathologic processes that compromise function of the peripheral nervous system include mechanical compression, ischemia, inflammation, and neoplasia.

Peripheral Nerve Tumors Most peripheral nerve tumors are benign and grow slowly. Significant pain increases the likelihood that the patient has a malignant tumor. Treatment for peripheral nerve tumors is surgical resection to establish diagnosis and evaluate for signs of malignancy. These tumors have various degrees of involvement with that parent nerve. Some can be resected with minimal or no damage to the nerve. Tumors that grow within the nerve often contain functioning fascicles. Total excision of these tumors requires sacrifice of the parent nerve. The choice of subtotal resection, nerve preservation, and observation, versus total resection with nerve sacrifice depends on tumor histology and the functions of the parent nerve.

Schwannoma Schwannomas are the most common peripheral nerve tumors, also referred to as neurilemomas or neurinomas. Most occur in the third decade of life. These benign tumors arise from Schwann cells, which form myelin in peripheral nerves. The most characteristic presentation is a mass lesion with point tenderness and shooting pains on direct palpation. Spontaneous or continuous pain suggests malignancy. They tend to grow slowly and eccentrically on the parent nerve. The eccentric location and discrete encapsulated nature of these tumors often allow total resection without significant damage to the parent nerve. Subtotal resection and observation is reasonable for schwannomas entwined in important nerves, as the incidence of malignant transformation is extremely low.

Neurofibroma Neurofibromas arise within the nerve and tend to be fusiform masses, unlike schwannomas, which tend to grow out of the nerve. Neurofibromas often present as a mass that is tender to palpation. They usually lack the shooting pains characteristic of schwannomas. Neurofibromas are often difficult to resect completely without sacrifice of the parent nerve. Neurofibromas have a higher incidence of malignant transformation, so patients with known residual tumors require close observation. Patients with von Recklinghausen’s neurofibromatosis often have multiple neurofibromas. These patients should be offered resection for symptomatic tumors. They also have a higher risk of malignant degeneration, up to 10%. Malignant neurofibromas have the histologic characteristics of sarcoma.

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for these tumors is radical excision. This often requires sacrifice of the parent nerve. Invasion of nearby soft tissues may occur and necessitate wide resection or amputation in an attempt to prevent systemic metastasis.

Entrapment Neuropathies Entrapment neuropathy is neurologic dysfunction in nerves passing through a pathologically small, fixed space. Nerve dysfunction may result directly from chronic, repetitive pressure on the nerve, or from ischemic damage due to impaired perfusion.15 Entrapment causing dysfunction of nerve signaling may cause numbness, paresthesias, weakness, or muscle atrophy. By far the two most common sites of entrapment neuropathy are the ulnar nerve at the medial aspect of the elbow and the median nerve at the wrist. Electomyography and nerve conduction studies (EMG/NCS) usually demonstrate slowing across the entrapped segment of nerve. Mechanical peripheral nerve disorders resulting from trauma (brachial plexus disruption, radial nerve damage from humerus fractures, and common peroneal nerve crush injuries) are discussed in the section on trauma.

Ulnar Neuropathy The ulnar nerve has contributions from the C7, C8, and T1 nerve roots, arises from the medial cord of the brachial plexus, and supplies most of the intrinsic hand muscles (interossei and third and fourth lumbricals), and sensation to the fourth and fifth digits. It passes posteriorly to the medial epicondyle at the elbow in the condylar groove. This segment is superficial and subject to external compression and repetitive minor impacts. Patients with ulnar entrapment at the elbow present with numbness and tingling in the medial palm and the fourth and fifth digits. Motor deficits include weakness and wasting of the intrinsic hand muscles. Treatment for symptomatic ulnar entrapment neuropathy is surgical exploration and incision of the fibrous aponeurotic arch that overlies the nerve. A 6-cm curvilinear incision between the medial epicondyle and the olecranon allows exploration of up to 10 cm of nerve and lysis of compressive tissues.

Carpal Tunnel Syndrome The median nerve has contributions from the C5 to T1 nerve roots, arises from the medial and lateral cords of the brachial plexus, and supplies the muscles of wrist and finger flexion and sensation to the palmar aspect of the first, second, and third digits. The median nerve passes through the carpal tunnel in the wrist, lying superficial to the four deep and four superficial flexor tendons. The transverse carpal ligament is a tough, fibrous band that forms the roof of the carpal tunnel. The ligament attaches to the pisiform and hamate medially and the trapezium and scaphoid laterally. Patients complain of numbness and tingling in the supplied digits, clumsiness, and worsening with sleep or repetitive wrist movement. Patients may notice wasting of the thenar eminence. Treatment for symptomatic carpal tunnel syndrome unresponsive to splinting, analgesics, and rest is surgical division of the flexor retinaculum. This often provides prompt relief of pain symptoms and slow recovery of numbness and strength.

Malignant Nerve Sheath Tumors Malignant nerve sheath tumors include solitary sarcomas, degenerated neurofibromas, and neuroepitheliomas. Patients with malignant peripheral nerve tumors typically complain of constant pain, rather than pain only on palpation, and are more likely to have motor and sensory deficits in the distribution of the parent nerve. Treatment

Autoimmune and Inflammatory Disorders These are not surgical diseases, but merit brief mention as they are included in the differential diagnosis for new-onset weakness. Their characteristic presentations help distinguish them from weakness due to structural lesions.

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Guillain-Barre´ Syndrome Guillain-Barr´e syndrome is an acute inflammatory demyelinating polyradiculopathy often occurring after viral infection, surgery, inoculations, or mycoplasma infections. Patients classically present with weakness ascending from the legs to the body, arms, and even cranial nerves. Symptoms usually progress over 2 to 4 weeks and then resolve. Care is supportive. Respiratory weakness may require ventilatory support.

Myasthenia Gravis Myasthenia gravis is an autoimmune process in which antibodies form to the acetylcholine receptors of muscles, leading to fluctuating weakness. Most patients have either thymic hyperplasia or thymoma. The most common symptoms are diplopia, ptosis, dysarthria, and dysphagia. More severe cases have limb or respiratory involvement. Weakness worsens with repetitive movement. Treatment is with acetylcholinesterase inhibitors and possible thymectomy.

Eaton-Lambert Syndrome Autoimmune process with antibodies to the presynaptic calcium channels. This is a paraneoplastic syndrome most commonly associated with oat cell carcinoma. Patients have weakness of proximal limb muscles that improves with repetitive movement. This diagnosis must prompt oncologic evaluation.

INFECTION Central nervous system infections of interest to neurosurgeons include those that cause focal neurologic deficit due to mass effect, require surgical aspiration or drainage because antibiotic therapy alone is insufficient, cause mechanical instability of the spine, or occur after neurosurgical procedures.

Cranial Osteomyelitis The skull is highly vascular and resistant to infections. Osteomyelitis of the skull may develop by contiguous spread from pyogenic sinus disease or from contamination by penetrating trauma. Staphylococcus aureus and S. epidermidis are the most frequent causative organisms. Patients usually present with redness, swelling, and pain. Contrast head CT aids diagnosis and shows the extent of involved bone, along with associated abscesses or empyema. Osteomyelitis treatment entails surgical d´ebridement of involved bone followed by 2 to 4 months of antibiotics. Craniotomy wound infections are a special concern because performing a craniotomy creates a devascularized free bone flap susceptible to infection and not penetrated by antibiotics. These wounds must be d´ebrided and the bone flaps removed and discarded. Subsequent care involves appropriate antibiotic therapy, observation for signs of recurrent infection off antibiotics, and return to the OR for titanium or methylmethacrylate cranioplasty 6 to 12 months later.

Subdural Empyema Subdural empyema is a rapidly progressive pyogenic infection. The subdural space lacks significant barriers to the spread of the infection, such as compartmentalization or septations. Subdural empyema usually occurs over the cerebral convexities. Potential infectious sources include sinus disease, penetrating trauma, and otitis. Streptococci and staphylococci are the most frequently found organisms. Presenting symptoms include fever, headache, neck

stiffness, seizures, or focal neurologic deficit. Neurologic deficit results from inflammation of cortical blood vessels, leading to thrombosis and stroke. The most common deficit is contralateral hemiparesis. Patients with suggestive symptoms should undergo rapid contrast CT scan. Lumbar puncture frequently fails to yield the offending organism and risks herniation due to mass effect. Typical treatment is wide hemicraniectomy, dural opening, and lavage. The pus may be thick or septated, making burr hole drainage or small craniotomy insufficient. Patients then require 1 to 2 months of antibiotics. Subdural empyema has 10 to 20% mortality and common chronic sequelae, including seizure disorder and residual hemiparesis. However, many patients make a good recovery.

Brain Abscess Brain abscess is encapsulated infection within the brain parenchyma. It may spread hematogenously in patients with endocarditis or intracardiac or intrapulmonary right-to-left shunts, by migration from the sinuses or ear, or via direct seeding by penetrating trauma. Disorganized cerebritis often precedes formation of the organized, walled-off abscess. Patients may present with nonspecific symptoms such as headache, nausea, or lethargy, or with focal neurologic deficit such as hemiparesis. Alternatively, patients may present in extremis if the abscess ruptures into the ventricular system. Abscesses appear as well-demarcated, ring-enhancing, thin-walled lesions on CT scan and MRI, and often have associated edema and mass effect. Patients require antibiotic therapy after needle aspiration or surgical evacuation. Antibiotic therapy without surgical evacuation may be considered for patients with small, multiple, or critically located abscesses. Abscesses that cause mass effect, decreased mental status, are large, or that fail to decrease in size after a week of antibiotics, should be evacuated. Nonsurgical management still requires aspiration or biopsy for organism culture and sensitivities. Blood and CSF cultures rarely give definitive diagnosis. Removal of an encapsulated abscess significantly shortens the length of antibiotic therapy required to eliminate all organisms. Common chronic sequelae after successful treatment include seizures or focal neurologic deficit.

Spine Pyogenic Vertebral Osteomyelitis Pyogenic vertebral osteomyelitis is a destructive bacterial infection of the vertebrae, usually of the vertebral body. Vertebral osteomyelitis frequently results from hematogenous spread of distant disease, but may occur as an extension of adjacent disease, such as psoas abscess or perinephric abscess. S. aureus and Enterobacter spp. are the most frequent etiologic organisms. Patients usually present with fever and back pain. Diabetics, IV drug abusers, and dialysis patients have increased incidence of vertebral osteomyelitis. Epidural extension may lead to compression of the spinal cord or nerve roots with resultant neurologic deficit. Osteomyelitis presents a lytic picture on imaging and must be distinguished from neoplastic disease. Adjacent intervertebral disc involvement occurs frequently with pyogenic osteomyelitis, but rarely with neoplasia. Plain films and CT help assess the extent of bony destruction or deformity such as kyphosis. MRI shows adjacent soft tissue or epidural disease. Most cases can be treated successfully with antibiotics alone, although the organism must be isolated to steer antibiotic choice. Blood cultures may be positive. Surgical intervention may be required for d´ebridement when antibiotics alone fail, or for stabilization and fusion in the setting of instability and deformity.

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Tuberculous Vertebral Osteomyelitis Tuberculous vertebral osteomyelitis, also known as Pott’s disease, occurs most commonly in underdeveloped countries and in immunocompromised people. Several features differentiate tuberculous osteomyelitis from bacterial osteomyelitis. The infection is indolent and symptoms often progress slowly over months. Tuberculosis rarely involves the intervertebral disc. The involved bodies may have sclerotic rather than lytic changes. Multiple nonadjacent vertebrae may be involved. Diagnosis requires documentation of acid-fast bacilli. Treatment involves long-term antimycobacterial drugs. Patients with spinal instability or neural compression from epidural inflammatory tissue should undergo d´ebridement and fusion as needed.

Discitis Primary infection of the intervertebral disc space, or discitis, is most commonly secondary to postoperative infections. Spontaneous discitis occurs more commonly in children. S. epidermidis and S. aureus account for most cases. The primary symptom is back pain. Other signs and symptoms include radicular pain, fevers, paraspinal muscle spasm, and localized tenderness to palpation. Many cases will resolve without antibiotics. Antibiotics are generally given for positive blood or biopsy cultures or persistent constitutional symptoms. Most patients will have spontaneous fusion across the involved disc and do not need d´ebridement or fusion.

Epidural Abscess Epidural abscesses may arise from or spread to the adjacent bone or disc, so distinguishing between vertebral osteomyelitis or discitis and a spinal epidural abscess may be difficult. The most common presenting signs and symptoms are back pain, fever, and tenderness to palpation of the spine. The most significant risk of epidural abscess is weakness progressing to paralysis due to spinal cord or nerve root damage. Cord and root damage may be due to direct compression or to inflammatory thrombosis resulting in venous infarction. S. aureus and Streptococcus spp. are the most common organisms. The source may be hematogenous spread, local extension, or operative contamination. MRI best demonstrates the epidural space and degree of neural compromise. Patients with suspected spinal epidural abscess should undergo surgical d´ebridement for decompression and diagnosis, followed by culture-directed antibiotic therapy. Relative contraindications to surgery include prohibitive comorbidities or total lack of neurologic function below the involved level. Patients with no neurologic deficits and an identified organism may be treated with antibiotics alone and very close observation. This is controversial, however, because these patients can undergo rapid and irreversible neurologic decline. Most epidural abscesses can be accessed via laminectomy without fusion. Collections predominantly anterior to the cervical or thoracic cord may require anterior approach and fusion.

FUNCTIONAL NEUROSURGERY Epilepsy Surgery Seizures result from uncontrolled neuronal electrical activity. Seizures may result from irritative lesions in the brain, such as tumors or hematomas, or from physiologic or structural abnormalities. Seizures may involve a part of the brain (focal) or the entire brain (generalized). Focal seizures may be associated with normal consciousness (simple) or decreased consciousness (complex). All

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generalized seizures cause loss of consciousness. Focal seizures may secondarily generalize. Patients with multiple unprovoked seizures over time have epilepsy. Epilepsy categorization depends on such factors as type of seizures, electroencephalographic (EEG) findings, associated syndromes, and identifiable etiologies. All patients with unexplained seizures (i.e., no obvious cause such as head trauma or alcohol withdrawal) or epilepsy require thorough neurologic evaluation, including imaging to evaluate for a mass lesion. Antiepileptic drugs (AEDs) form the first line of therapy for epilepsy, initially as monotherapy, then as combination therapy. Epilepsy patients who have failed satisfactory trials of several AED combination regimens may be candidates for surgical intervention. Lack of seizure control or patient intolerance of the medications may constitute failure. Epilepsy surgery can decrease the frequency of seizures by resection of the electrical source of the seizures, or decrease the severity of seizures by severing white matter tracts through which the abnormal electrical activity spreads. Three types of epilepsy surgery are discussed. Epilepsy surgery appears to be extremely underutilized, given the relatively low risk of the procedures, and the crippling social and economic effects of uncontrolled or partially controlled epilepsy.16 Patients with symptoms, imaging abnormalities, and EEG analysis compatible with a specific seizure focus are most likely to have good results from epilepsy surgery.

Anterior Temporal Lobectomy Medial temporal lobe structural abnormalities can lead to complex partial seizures (CPS). Many patients with CPS have poor seizure control on medications. Patients with CPS may have significant reduction in seizure frequency or cessation of seizures after resection of the anterior temporal lobe. The amygdala and the head of the hippocampus are removed as part of the lobectomy. Resection may be taken back approximately 4.5 cm from the temporal tip in the language-dominant hemisphere, and 6 cm from the temporal tip in the language nondominant hemisphere, with low risk of significant deficits.17 Two main risks of anterior temporal lobectomy are memory problems and visual problems. Removal of the hippocampus in a patient with an atrophied or nonfunctional contralateral hippocampus causes a global memory deficit. Interruption of the optic radiations, which carry visual signals from the contralateral superior visual quadrants of both eyes, causes a contralateral superior quadrantanopia, known as a “pie in the sky” field deficit.

Corpus Callosotomy Patients with generalized seizures, atonic seizures associated with drop attacks, or absence seizures, who are found to have bilaterally coordinated pathologic cortical discharges on EEG, and who fail AED therapy may be candidates for corpus callosotomy. The corpus callosum is a large white matter tract that connects the cerebral hemispheres. Loss of consciousness requires simultaneous seizure activity in both hemispheres. Focal or partial seizures may spread via the corpus callosum to the contralateral hemisphere, causing generalization and loss of consciousness. Division of the corpus callosum can interrupt this spread. Patients may have decreased numbers of seizures and/or fewer episodes of lost consciousness. Usually only the anterior half or two-thirds of the corpus callosum is divided, as more extensive division increases the risk of disconnection syndrome. Patients with disconnection syndrome are unable to match objects in the opposite visual hemifields, to identify objects held in one hand with the other hemifield, and to write with the left hand or name objects held in the left hand (in left hemisphere–dominant patients).

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Hemispherectomy Children with intractable epilepsy, structural anomalies in one hemisphere, and contralateral hemiplegia, may have improved seizure control after resection of the hemisphere (anatomic hemispherectomy) or disruption of all connections to the hemisphere (functional hemispherectomy). Functional hemispherectomy is often preferred over anatomic hemispherectomy because of the high incidence of complications such as hematoma formation and ventriculoperitoneal shunt dependence associated with the latter.

Deep Brain Stimulators Patients with essential tremor and medically refractory Parkinson’s disease have abnormal activity in the nuclei of the basal ganglia. The basal ganglia are extrapyramidal structures that modulate and regulate signals in the corticospinal (pyramidal) tracts. Abnormal extrapyramidal activity leads to the loss of the normal modulation of movement and thus the clinical manifestations of the diseases. Fine electrical leads placed in these deep basal ganglia nuclei and connected to pulse generators modify the pathologic signals. The pulse generators are usually placed in the chest in a manner similar to cardiac pacemakers. Connector wires travel from the generators in the subcutaneous space up the neck and in the subgaleal space in the head, to connect the pulse generators to the electrical leads. Proper lead placement is accomplished with stereotactic guidance. A frame is rigidly locked to the patient’s head and an MRI is obtained with the frame in place. Calculation of the coordinates of the millimeter-sized deep brain nuclei in relation to the three-dimensional space defined by the fixed frame allows accurate targeting, and the fine electrical leads are placed within the desired nuclei (Fig. 41-32). Postoperatively the pulse generators can be interrogated and adjusted with hand-held, transcutaneous, noninvasive devices as needed for symptom control.

Essential Tremor Essential tremors are action tremors of 4 to 8 Hz rhythmic oscillation that often affect one arm or the head. Essential tremor often

starts in the third or fourth decade of life, and increases in frequency and amplitude with age. Beta blockers decrease symptoms. Patients with poor medical control and significant functional impairment can benefit significantly from placement of a deep brain stimulator in the contralateral ventrointermediate nucleus (VIN) of the thalamus. Placement of VIN stimulators for essential tremors appears to result in durable symptom control with good postoperative neuropsychologic outcomes in properly selected patients.18,19

Parkinson’s Disease Parkinson’s disease is a progressive disorder characterized by rigidity, bradykinesia, and resting tremor, due to loss of dopaminesecreting neurons in the substantia nigra and locus ceruleus. It is also known as paralysis agitans. Dopaminergic agents such as levodopa/carbidopa and anticholinergic agents such as amantadine and selegiline form the basis of medical therapy. Patients with poor medical control or significant drug side effects may benefit significantly from placement of bilateral deep brain stimulators in the subthalamic nuclei (STN) or globus pallidus pars interna (GPi). Debate continues regarding the relative efficacy of each target.20 A blinded trial is currently underway through the Veteran’s Administration Parkinson’s Disease Research, Education, and Clinical Centers (PADRECCs) comparing outcomes with STN and GPi stimulation. Deep brain stimulation seems to provide durable symptom relief with good postoperative neuropsychologic function in properly selected patients.21

Trigeminal Neuralgia Trigeminal neuralgia, also known as tic douloureux, is characterized by repetitive, unilateral, sharp and lancinating pains in the distribution of one of the three branches of cranial nerve V, the trigeminal nerve. The patient may describe a “trigger point,” an area on the face that elicits the pain when touched. A current leading etiologic hypothesis for trigeminal neuralgia is irritation and pulsatile compression of the root entry zone of the nerve by an artery in the posterior fossa, usually a loop of the superior cerebellar artery. The pain is excruciating and can be debilitating. Medical therapy, including carbamazepine and amitriptyline, may reduce the frequency of events. Options for medically refractory cases include percutaneous injection of glycerol into the path of the nerve, peripheral transection of the nerve branches, stereotactic radiosurgery, and microvascular decompression (MVD). MVD involves performing a small posterior fossa craniotomy on the side of the symptoms, retraction of the cerebellar hemisphere, and exploration of cranial nerve V. If an artery is found near the nerve, the vessel is freed of any adhesions and nonabsorbable material is placed between the nerve root and the artery. MVD remains the first definitive management option because stereotactic radiosurgery is associated with a high incidence of facial numbness.22

STEREOTACTIC RADIOSURGERY

FIG. 41-32. Fast spin echo coronal MRI demonstrating position of deep brain stimulator leads in the subthalamic nuclei bilaterally. The electrodes appear thick and wavy due to magnetic susceptibility artifact.

The term stereotactic radiosurgery (SRS) refers to techniques that allow delivery of high-dose radiation that conforms to the shape of the target and has rapid isodose fall-off, minimizing damage to adjacent neural structures. The two most common devices used for conformal SRS for intracranial lesions are the LINAC (linear accelerator) and the gamma knife. LINAC delivers a focused beam of x-ray radiation from a port that arcs partway around the patient’s head. Linear accelerators are commonly used to provide fractionated radiation for lesions outside the CNS. They are found in most radiation oncology departments. SRS can be performed with these

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existing units, after upgrades to the software and collimators. The gamma knife delivers approximately 200 focused beams of gamma radiation from cobalt sources through a specially designed colanderlike helmet. Gamma knife units are used only for intracranial disease and cost up to $5 million; thus they are most appropriate in high patient–volume centers. There is ongoing debate in the literature regarding the two technologies.23–25 Both continue to evolve, allowing more precise and complex isodose conformation to complex lesions. Most lesions can be treated equally well with either technology. Lesions abutting the medulla or the spinal cord should not be treated with SRS, because these structures do not tolerate the radiation dose delivered to structures within millimeters of the target. Also, medullary or spinal cord compression can result from swelling of the lesion after the radiosurgery dose, resulting in devastating neurologic deficit.

Arteriovenous Malformations SRS has been found to be an effective stand-alone therapy for AVMs up to 3 cm in diameter. SRS is best for lesions that are difficult to access surgically due to high likelihood of postoperative neurologic deficit. SRS is not effective for lesions larger than 3 cm. Effective obliteration and elimination of the risk of hemorrhage takes 2 years. There is an approximately 2% annual incidence of hemorrhage during this 2-year period.26 Thus surgical excision remains the preferred therapeutic modality, with SRS reserved for cases deemed very highrisk for surgery due to location or patient factors.27 Some patients with large AVMs who undergo surgery will have unresectable residual lesions. SRS may be used as an effective adjunctive therapy in these patients.

Vestibular Schwannomas SRS has been introduced as a therapeutic alternative to microsurgical resection for vestibular schwannomas up to 2.5 cm in maximum diameter. SRS provides high rates of tumor growth arrest and possible reduction in size with low rates of facial nerve palsy. Patients with functional ipsilateral hearing preprocedure may be more likely to retain functional hearing postprocedure than with microsurgery. The limitations of SRS include inability to treat tumors larger than 2.5 cm, the possibility of radiation-induced malignant transformation of these benign tumors, and lack of long-term follow-up. SRS centers are accumulating experience with these tumors and accumulating data on long-term results.28,29 The indications for microsurgery and SRS will continue to evolve. Either approach should be undertaken at a high-volume center, as studies show the patient outcomes improve with increased surgeon experience.30

Intracranial Metastases Patients with solitary or multiple intracranial metastases may be treated primarily with SRS.31 Patients have improved survival after SRS compared to no treatment or whole-brain radiation therapy (WBRT), and similar survival to patients undergoing total surgical resection. Patients with lesions greater than 3 cm in diameter or evidence of intracranial hypertension should undergo surgical decompression rather than SRS. Some studies show improved survival with up to seven intracranial masses. Patients with multiple intracranial masses have almost zero long-term survival, and most will die of their intracranial disease. Patients with intracranial metastases live 3 to 6 months on average with medical care and WBRT. This can be extended to 9 to 16 months with SRS or surgery, depending on tumor type, age, and patient condition.32

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CONGENITAL AND DEVELOPMENTAL ANOMALIES Dysraphism Dysraphism describes defects of fusion of the neural tube involving the neural tube itself, or overlying bone or skin. Dysraphism may occur in the spine or the head. Neural tube defects are among the most common congenital abnormalities. Prenatal vitamins, especially folic acid, reduce the incidence of neural tube defects.

Spina Bifida Occulta Spina bifida occulta is congenital absence of posterior vertebral elements. The spinous process is always missing, the laminae may be missing to various degrees, but the underlying neural tissues are not involved. Spina bifida occulta is found in 25% of the general population, and is asymptomatic unless associated with other developmental abnormalities.

Spina Bifida with Myelomeningocele Spina bifida with myelomeningocele describes congenital absence of posterior vertebral elements with protrusion of the meninges through the defect, and underlying neural structural abnormalities. Common findings are weakness and atrophy of the lower extremities, gait disturbance, urinary incontinence, and deformities of the foot. Myelomeningoceles arising from the high lumbar cord usually cause total paralysis and incontinence, while those arising from the sacral cord may have only clawing of the foot and partial urinary function. Myelomeningocele patients often have hydrocephalus and a Chiari II malformation, an abnormal downward herniation of the cerebellum and brain stem through the foramen magnum. Patients with abnormal protrusion of meninges through the bony defect without abnormalities of the underlying neural tissue have a meningocele. Most of these patients are neurologically normal.

Encephalocele Herniation of brain encased in meninges through the skull that forms an intracranial mass is referred to as encephalocele. Herniation of meninges without brain tissue is referred to as a meningocele. Most occur over the convexity of the skull. More rarely, the tissue protrudes through the skull base into the sinuses. Treatment involves excision of the herniated tissue and closure of the defect. Most patients with encephaloceles and meningoceles have impaired cognitive development. Patients with greater amounts of herniated neural tissue tend to have more severe cognitive deficits.

Craniosynostosis Craniosynostosis is the abnormal early fusion of a cranial suture line with resultant restriction of skull growth in the affected area and compensatory bulging at the other sutures. Skull growth occurs at the cranial sutures for the first 2 years of life, at the end of which the skull has achieved over 90% of its eventual adult size. Fusion of the sagittal suture, or sagittal synostosis, results in a boat-shaped head, known as scaphocephaly. Unilateral coronal synostosis results in ipsilateral forehead flattening and outward deviation of the orbit, known as plagiocephaly. The contralateral normal forehead appears to bulge by comparison. Bilateral coronal synostosis results in a broad, flattened forehead, known as brachycephaly, and is often associated with maxillary hypoplasia and proptosis. Unilateral or bilateral lambdoid synostosis results in flattening of the occiput. Occipital flattening can result from abnormal suture fusion (synostosis), or from physical remolding of the skull caused by always

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SCHWARTZ’S PRINCIPLES OF SURGERY/SPECIFIC CONSIDERATIONS

A

B

FIG. 41-33. A . Axial head CT scan revealing dilated ventricular system. Note dilated atria of the lateral ventricles (arrowheads) and rounded third ventricle (arrow). The large size of the ventricles and lack of transependymal flow indicate a chronic process (contrast to Fig. 41-2). The patient has normal-pressure hydrocephalus, and had improved ambulation after placement of a ventriculoperitoneal shunt. B . Higher cut from same scan showing ventricular catheter in place in the frontal horn of the right lateral ventricle.

placing the baby in the supine position for sleep (known as positional plagiocephaly). Placing the baby in the prone position or tilted onto the contralateral side may restore near-normal skull shape in most cases of lambdoid synostosis, avoiding surgery. Treatment for synostoses in general is surgical, involving resection of the fused suture, or more complex reconstructive techniques for severe or refractory cases.

Hydrocephalus Excess CSF in the brain that results in enlarged ventricles is known as hydrocephalus. The adult forms approximately 500 mL of CSF per day, much of it in the lateral ventricles. CSF flows from the ventricles to the subarachnoid space, and is then absorbed into the venous blood through the arachnoid granulations. Hydrocephalus may be classified as communicating or obstructive (outlined below), and congenital or acquired. Congenital lesions associated with or causing hydrocephalus include stenosis of the cerebral aqueduct, Chiari malformations, myelomeningoceles, and intrauterine infections. Acquired hydrocephalus may result from occlusion of arachnoid granulations by meningitis or subarachnoid hemorrhage, or occlusion of CSF pathways by adjacent tumors (Fig. 41-33).

Communicating Hydrocephalus Obstruction at the level of the arachnoid granulations constitutes communicating hydrocephalus. This usually causes dilation of the lateral, third, and fourth ventricles equally. The most common causes in adults are meningitis and subarachnoid hemorrhage. Hydrocephalus may be transient after subarachnoid hemorrhage,

with reestablishment of normal CSF absorption after the protein content of the CSF returns to normal and the granulations reopen.

Obstructive Hydrocephalus Obstruction of CSF pathways is known as obstructive hydrocephalus. Ventricles proximal to the obstruction dilate, while those distal to the obstruction remain normal in size. Typical patterns include dilation of the lateral ventricles due to a colloid cyst occluding the foramen of Monro, dilation of the lateral and third ventricles due to a tectal (midbrain) glioma or pineal region tumor occluding the cerebral aqueduct, or dilation of the lateral and third ventricles with obliteration of the fourth ventricle by an intraventricular tumor of the fourth ventricle. Obstructive hydrocephalus may present precipitously and require urgent shunting to prevent herniation.

Chiari I Malformation Chiari I malformation is the caudal displacement of the cerebellar tonsils below the foramen magnum, and may be seen as an incidental finding on MRI scans in asymptomatic patients. Symptomatic patients usually present with headache, neck pain, or symptoms of myelopathy, including numbness or weakness in the extremities. The brain stem and lower cranial nerves are normal in Chiari I malformations. Chiari II malformations are more severe and involve caudal displacement of the lower brain stem and stretching of the lower cranial nerves. Symptomatic patients may be treated with suboccipital craniectomy to remove the posterior arch of the foramen magnum, along with removal of the posterior ring of C1. Removal of these bony structures relieves the compression of the cerebellar

41/NEUROSURGERY

12.

13.

14.

15. 16.

17. 18. 19.

FIG. 41-34. T1-weighted sagittal MRI of a patient with a Chiari I malformation. The large arrowhead points to the cerebellar tonsils. The small arrow points to the posterior arch of the foramen magnum.

20.

21.

tonsils and cervicomedullary junction, and may allow reestablishment of normal CSF flow patterns. Figure 41-34 demonstrates typical MRI appearance of a Chiari I malformation. References 1. Kandel E, Schwartz J, Jessell T: Principles of Neural Science, 3rd ed. New York: Elsevier, 1991, p. 961. 2. Masters SJ, McClean PM, Aracarese JS, et al: Skull x-ray examination after head trauma. N Engl J Med 316:84, 1987. 3. Stein SC, Ross SE: The value of CT scans in patients with low-risk head injuries. Neurosurgery 26:638, 1990. 4. Ingebrigsten R, Romner B: Routine early CT scan is cost-saving after minor head injury. Acta Neurol Scand 93:207, 1996. 5. Kelly JP, Nichols JS, Filley CM: Concussion in sports: Guidelines for the prevention of catastrophic outcome. JAMA 266:2867, 1991. 6. Howard MA, Gross AS, Dacey RG, et al: Acute subdural hematomas: An age-dependent clinical entity. J Neurosurg 71:856, 1989. 7. Maynard FM, Bracken MB, Creasey G, et al: International Standards for Neurological and Functional Classification of Spinal Cord Injury. American Spinal Injury Association. Spinal Cord 35:266, 1997. 8. Bracken MB, Shepard MJ, Collins WF, et al: A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal cord injury. N Engl J Med 322:1405, 1990. 9. Bracken MB, Shepard MJ, Collins WF, et al: Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-Year follow up data. J Neurosurg 76:23, 1992. 10. Hugenholts H, Cass DE, Dvorak MF, et al: High-dose methylprednisolone for acute closed spinal cord injury—only a treatment option. Can J Neurol Sci 29:227, 2002. 11. North American Symptomatic Carotid Endarterectomy Trial Collaborators: Beneficial effects of carotid endarterectomy in symptomatic

22. 23.

24.

25. 26.

27. 28.

29. 30.

31.

32.

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patients with high-grade carotid stenosis. N Engl J Med 325:445, 1991. The National Institute of Neurologic Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581, 1995. Monylneux A, Kerr R, Stratton I, et al: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised trial. Lancet 360:1267, 2002. Raftopoulos C, Goffette P, Vaz G, et al: Surgical clipping may lead to better results than coil embolization: Results from a series of 101 consecutive unruptured intracranial aneurysms. Neurosurgery 52:1280, 2003. Dawson D, Hallett M, Wilbourn A: Entrapment Neuropathies, 3rd ed. Baltimore: Lippincott-Raven, 1999, Chap 2, p 4. Benbadis S, Heriaud L, Tatum WO, et al: Epilepsy surgery, delays and referral patterns—are all your epilepsy patients controlled? Seizure 12:167, 2003. Rausch R, et al: Early and late cognitive changes following temporal lobe surgery for epilepsy. Neurology 60:9551, 2003. Rehncrona S, et al: Long-term efficacy of thalamic deep brain stimulation for tremor: Double-blind assessments. Move Disord 18:163, 2003. Fields J, Troster AI, Woods SP, et al: Neuropsychologic and quality of life outcomes 12 months after unilateral thalamic stimulation for essential tremor. J Neurol Neurosurg Psychiatry 74:305, 2003. Krause M, Fogel W, Heck A, et al: Deep brain stimulators for the treatment of Parkinson’s disease: Subthalamic nucleus versus globus pallidus internus. J Neurol Neurosurg Psychiatry 70:464, 2001. Perozzo P, Rissone M, Bergamoasco B, et al: Deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: Comparison of pre- and post-operative neuropsychologic evaluation. J Neurol Sci 193:9, 2001. Kondo A: Microvascular decompression surgery for trigeminal neuralgia. Stereotactic and Functional Neurosurgery 77:187, 2001. Suh J, Barnett GH, Miller DW, et al: Successful conversion from a linear accelerator-based program to a gamma knife radiosurgery program: The Cleveland Clinic experience. Stereotactic and Functional Neurosurgery 72(Suppl 1):159, 1999. Konigsmaier H, de Pauli-Ferch B, Hackl A, et al: The costs of radiosurgical treatment: Comparison between gamma knife and linear accelerator. Acta Neurochir 140:1101, 1998. Bova J, Goetsch S: Modern linac [linear accelerator] radiosurgery systems have rendered the gamma knife obsolete. Med Phys 28:1839, 2001. Karlsson B, Lax I, Soderman M: Risk for hemorrhage in the 2-year latency period following gamma-knife radiosurgery for AVM. Int J Radiation Oncol Biol Phys 49:1045, 2001. Pan D, Guo WY, Chung WY, et al: Gamma knife radiosurgery as a single treatment modality for large cerebral AVMs. J Neurosurg 93:113, 2000. Regis J, Pellet W, Delsanti C, et al: Functional outcome after gamma knife surgery or microsurgery for vestibular schwannomas. J Neurosurg 97:1091, 2002. Shim M, Ueki K, Kurita H, et al: Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 360:309, 2002. Elsmore A, Mendoza N: The operative learning curve for vestibular schwannoma excision via the retrosigmoid approach. Br J Neurosurg 16:448, 2002. Gerosa M, Nicolato A, Foroni R, et al: Gamma knife radiosurgery for brain metastases: A primary therapeutic option. J Neurosurg 97:515, 2002. Pollock B, Brown PD, Foote RL, et al: Properly selected patients with multiple brain metastases may benefit from aggressive treatment of their intracranial disease. J Neurooncol 61:73, 2003.

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CHAPTER

42

Orthopaedics Dempsey Springfield

Skeletal Growth and Physiology Joint Anatomy and Physiology Muscle Anatomy and Physiology Basic Biomechanics Tumors of the Musculoskeletal System General Considerations Specific Musculoskeletal Tumors Bone-Forming Tumors Cartilaginous Tumors Fibrous Lesions Cystic Lesions Round Cell Tumors Other Tumors Vascular Tumors Tumors Arising from Included Tissues Soft-Tissue Sarcoma Metastatic Bone Tumors Evaluation of the Musculoskeletal System History and Physical Examination Radiology Diagnostic Injections Disorders of the Musculoskeletal System Osteomyelitis Pyogenic Arthritis Arthritis Osteoarthritis Rheumatoid Arthritis Miscellaneous Arthritides Infectious Arthritis Trauma Initial Assessment Open Fractures Goals of Treatment of Musculoskeletal Injuries Principles of Treatment Terminology Pelvic Fractures Acetabular Fractures Hip Dislocation Anterior Hip Dislocations Posterior Hip Dislocations Femur Fractures Femoral Neck Fractures Intertrochanteric and Subtrochanteric Fractures Fractures of the Femoral Shaft Distal Femur Fractures

Patella Fractures Tibial Plateau Fractures Tibial Shaft Fractures Ankle Injury Talus Calcaneus Midfoot Injury Metatarsal Fractures Toes Clavicle Acromioclavicular Separation Anterior Shoulder Dislocation Chronic Dislocation Posterior Shoulder Dislocation Proximal Humerus Fractures Humeral Shaft Fractures Elbow Fractures Forearm Fractures Distal Radius Fractures Spinal Injuries Cervical Spine Joint Replacement Surgery Total Hip Replacement Total Knee Replacement Shoulder Disorders Rotator Cuff and Biceps Tendon Frozen Shoulder Glenohumeral Instability Glenohumeral Arthritis Elbow Disorders Spine Disorders Low Back Pain Neck Pain Alignment Disorders Muscle and Tendon Injuries The Athletic Knee Meniscal Injuries Ligament Injuries Anterior Cruciate Ligament Posterior Cruciate Ligament Collateral Ligaments The Dislocated Knee Articular Cartilage Injuries Foot and Ankle Disorders Tendon Disorders

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Heel Pain Hallux Valgus Lesser-Toe Deformity Stress Fractures Arthritis Ankle Instability Diabetic Foot Interdigital Neuroma Tarsal Tunnel Syndrome Pediatric Disorders Developmental Dysplasia of the Hip Slipped Capital Femoral Epiphysis Legg-Calv´e-Perthes Disease Talipes Equinovarus Metatarsus Adductus Tarsal Coalition Blount Disease Osgood-Schlatter Disease

Nicolas Andry coined the word from which the English word orthopaedics is derived when he wrote a book titled L’Ortho’edie in 1741. Orthopaedics is derived from the two Greek words Andry chose: orthos, meaning straight or free from deformity, and pais, meaning child. Since that time orthopaedics has expanded to include the evaluation and treatment of all musculoskeletal injury and disorders. Until the later half of the twentieth century, orthopaedics was predominately the nonoperative treatment of fractures, treatment of musculoskeletal infections (often tuberculosis), and polio. As we enter the twenty-first century, orthopaedic surgery includes the replacement of degenerated joints, operative fixation of fractures, arthroscopic repair of torn meniscus, rotator cuffs, and a whole host of other intra-articular abnormalities. Musculoskeletal research laboratories have found means of stimulating the body to make new bones and soon cartilage production will be accomplished. Gene therapies for a variety of musculoskeletal diseases are on the horizon. Orthopaedics is a dynamic field and orthopaedic surgeons treat both sexes and all ages of patients with a wide variety of skeletal, ligamentous, and muscular problems. Orthopaedics are involved in the management of a newborn’s dislocated hip, a teenager’s curved spine, an athlete’s injury knee, a motor vehicle accident victim, an adult’s worn-out joint, and an elderly woman’s fracture hip.1−5 The musculoskeletal system is a complex biomechanical organ. It is constantly responding to the demands of the patient. Bone is in constant turnover. It atrophies when not used, and hypertrophies when stressed. Overall bone mass is increased until some time between 30 and 35 years of age, after which there is an overall decrease of bone as a consequence of more resorption than production. Bone can heal without leaving a scar. Articular cartilage is a special material because it has properties that people have not been able to reproduce. It is a wonderful shock absorber, yet when sliding with another surface of articular cartilage bathed in normal synovial fluid, the constant of friction is a fraction of that found with ice-on-ice. Unfortunately, upon reaching adulthood, the ability to generate new articular cartilage ceases and as it wears out or is injured, it is not replaced. Repair fibrocartilage, metal, and plastic are the materials currently substituted for articular cartilage. Skeletal muscle accounts for almost 50% of the body’s weight making it the single largest tissue mass in the human body. There is one basic structural unit in muscle fiber; however, the arrangement of these

fibers varies depending on a particular muscle’s function. Muscle fibers are either parallel or oblique with oblique fibers existing in various configurations.

SKELETAL GROWTH AND PHYSIOLOGY The skeletal system is initially formed as cartilage with the exception of the craniofacial bones and clavicle. These bones do not have a cartilaginous analogue and are formed directly from membranous tissue. The process of bone formation without an intermediate cartilage form is called intramembranous bone formation. The majority of an adult’s bone is formed by intramembranous bone formation because diaphyseal bone grows circumferentially by the apposition of bone by the surrounding periosteum without cartilage being produced. Enchondral ossifications is the formation of bone through the initial formation of a cartilage model that then becomes bone. The skeletal system is formed in utero as cartilage; however, prior to birth, some of these prebone structures are well on their way to bone formation. This happens first in the middle of the diaphysis, known as the primary center of ossification. Later, at the secondary ossification center, bone will begin to form at the ends of the prebone structures. The secondary center of ossification has articular cartilage surrounding it on the side facing the joint and epiphyseal cartilage on the side facing the primary ossification center. The bone grows in length through the epiphyseal growth plate, which produces cartilage that undergoes enchondral ossification (Fig. 42-1). The epiphyseal growth plate is made up of proliferating cartilage cells that eventually die. After the cartilage cells die, osteoblasts line the calcified cartilage matrix previously produced by the chondrocytes, thus forming bone. The epiphyseal growth plate is divided into zones. The number of zones often varies in the literature dependent upon the author; however, a general consensus specifies five zones. The first zone is the resting or reserve zone, followed by the proliferative zone, the maturation zone, the degeneration zone, and the zone of calcification. The zones of maturation, degeneration, and calcification are often referred to as the hypertrophic zone. The initial bone formed consists of spicules of bone with a calcified cartilaginous core and is called the primary spongiosa. The calcified cartilage will be removed entirely as the bone continues to remodel. The area of the bone with the primary spongiosa is called the metaphysis. This bone remodels to become the narrower diaphysis (Fig. 42-2). The initial bone formed during this process is referred to as woven bone. This bone is unorganized both grossly and microscopically. As it remodels and matures, it becomes lamellar bone. It can be either cortical bone with a blood supply and a Haversian system, or trabecular bone, which does not have a Haversian system (Fig. 42-3). Bone is produced by osteoblasts, which become osteocytes once they are trapped within a matrix of bone. Osteoclasts are multinucleated cells that have the capability of resorbing bone. Osteoblast and osteocytes are recognized under the microscope by the matrix they produce. Chondrocytes are cells responsible for making cartilage and live within the cartilage matrix. (Use of the term chondroblast for the cartilage-producing cells lining a surface of cartilage production is appropriate, but rarely used.) Bone remodels constantly, primarily under the influence of a mechanical load. During the first 30 years of life, a person’s overall skeletal mass perpetually increases; however, after 30 years of age, overall skeletal mass decreases, with women experiencing a period of accelerated loss just after menopause (Fig. 42-4). The more bone an individual has acquired by age 30, the less likely she or he are to develop osteoporosis.

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GROWTH PLATE

High p02

RESTING ZONE PROLIFERATIVE ZONE Cell Division, Matrix Synthesis PTHr Receptor Expression Gr. Hormone IGF-I Production bFGF, TGFβ Expression

HYPERTROPHIC ZONE Type X Collagen TGFβ, PTHrP Expression 5-10x Size Increase Matrix Vesicles, Production Alkaline Phosphotase

Low p02

ZONE OF PROVISIONAL CALCIFICATION Matrix Vesicles Initiate Matrix Calcification Chondrocytes Undergo Apoptosis

FIG. 42-1. Structure and function relationships of the growth plate. Calcified cartilage bars form scaffold for osteoblasts to deposit new bone; osteoclast-like cells reabsorb calcified cartilage through remodelling.

Osteoporosis is defined as a loss of bone per unit of volume. A more strict definition is bone with a bone mineral density (BMD) as measured by a dual-energy x-ray absorptiometry (DEXA) scan of more than 2.5 below the norm. The norm is based on a series of

2nd Ossification Center

Epiphysis

Metaphysis

Diaphysis

FIG. 42-2. Long bones have three sections. The end is the epiphysis or secondary ossification center, the adjacent area is the metaphysis, and the middle of the bone is the diaphysis. The metaphysis is broader than the diaphysis, has a thin cortex, and is composed of primarily cancellous bone.

bone mineral density analyses done on healthy women who were at the peak bone mass. Osteomalacia (disorder in adults) and rickets (disorder in children) are the inadequate mineralization of bone. Osteopenia is the term used to describe the radiographic appearance of a bone with less density than expected. Osteoporosis should be prevented by having young persons, especially women, take adequate amounts of calcium and vitamin D, as well as exercise to build their skeletal system to its maximum. Osteomalacia is treated by restoring a normal calcium metabolism. Abnormal calcium metabolism may be caused by a congenital disorder, dietary abnormalities, gastrointestinal disorders, by-pass surgery, parathyroid dysfunction, or renal disease.

JOINT ANATOMY AND PHYSIOLOGY A diarthrodial joint is one in which a complete separation between the connecting parts is present. The diarthrodial joint contains synovial fluid, which lubricates the two articular cartilage-covered surfaces that rub against one another. Articular cartilage is unique in that its coefficient of friction between the two articular surfaces with normal synovial fluid is estimated to be 10 times less than that which exists between two blocks of ice. This allows free movement with little wear of the articular surfaces. The amount of articular cartilage achieved upon completing growth (mid-teenage years) is the total amount a person will possess for the remainder of life. Once damaged, it cannot be replaced. Repair cartilage (fibrocartilage) can look similar and even have similar (not identical) properties, but does not have the mechanical properties to withstand the high demands placed on a joint surface. Additionally, fibrocartilage wears out within a few years when it is subjected to the forces experienced across a normal joint. Research continues in an effort to better understand cartilage in order to replace damaged portions before the entire joint is destroyed. Articular cartilage is composed of hyaline cartilage, which is between 60 and 80% water. The remaining composition consists of macromolecules—collagen, proteoglycans, and noncollagenous

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Bone Marrow Cavity

Endosteal Surface

Trabecular Bone

Resorption Cavity Volkmann's Canal

Lamellar Bone Cutting Cone

Howship's Lacunae Osteocyte

Periosteum

Haversian Canal (Osteons)

FIG. 42-3. The cellular and structural organization of bone.

clinical evidence of healing. If the injury includes the subchondral bone it will bleed, thus producing a healing response; however, the restorative cartilage made is not identical to the original articular cartilage and does not function in the same manner because it wears too quickly and does not hold up to the type of stresses normally experienced by a joint. Degenerative arthritis or osteoarthritis is the wearing away of articular cartilage. It can occur secondary to an injury, from malalignment leading to abnormal forces, from numerous conditions that interfere with the synovial lining from doing its job, or for no apparent reason. Idiopathic or osteoarthritis of old age is the most common form. The hallmark of degenerative arthritis is a loss of articular cartilage. The bone immediately under the articular cartilage (subchondral bone) hypertrophies and the peripheral cartilage responds to produce osteophytes. Osteophytes are osteocartilaginous at the periphery of the joint (Fig. 42-5). A degenerative pattern is seen as the end stage of the inflammatory arthritides such as in rheumatoid arthritis. The synovium is critical to the normal function of the joint as it provides synovial fluid, which surrounds the joint that is necessary to maintain the extremely low coefficient of friction between

BONE MASS

proteins—which are all composed of amino acids and sugars. Type II collagen accounts for approximately 95% of the collagen in articular cartilage. There are three major proteoglycans in articular cartilage that are all polysaccharide chains with a protein core. The two larger proteoglycans are referred to as aggrecans, which, along with water, fill the interfibrillar spaces and give cartilage its mechanical properties. One contains mainly chondroitin sulfate and the other mainly keratin sulfate. A smaller one contains mainly dermatan sulfate. Articular cartilage is organized into four zones or layers; superficial or gliding, middle or transitional, deep or radial, and calcified. Each has its own organization, collagen and proteoglycan contents, and function. Disruption of any layer causes the articular cartilage to malfunction. There are many other minor proteins in articular cartilage that are critical to the normal function of the cartilage. The extremely limited healing ability of cartilage is in direct contrast to that of bone. Bone has the capacity to not only heal after an injury but the ability to heal without a scar. Cartilage does not heal. An injury to articular cartilage will be followed by a response of the chondrocytes, but the response is limited and will not heal any injury. If the injury, including a laceration, is superficial and does not include the underlying subchondral bone, there will be no

Osteoclastic Resorption

"Spontaneous Fracture Rise"

10

50 AGE (YEARS)

70 Average

FIG. 42-4. Until the age of 30 to 35 years bone mass increases, but from then on it decreases. For women there is an acceleration of loss associated with menopause.

FIG. 42-5. Bilateral osteoarthritis of the hips showing marked osteophyte formation, sclerosis, acetabular cysts, obliteration of joint space, and partial subluxation.

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Table 42-1 Synovial Fluid Analysis Clinical Example

Normal

Noninflammatory (Osteoarthrosis)

Inflammatory (Rheumatoid)

Septic (Bacterial)

Color Viscosity WBC/mm3 % PMM leukocytes Culture Mucin clot Glucose (% of serum glucose) Total protein

Clear High 200 100,000 >75% Positive Friable