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Second Edition

Edited by Graeme J. Poston, Michael DAngelica, and Ren Adam


About the book
Hepato-Pancreato-Biliary (HPB) surgery is now firmly established within the repertoire
of modern general surgery. This new edition has been completely rewritten by
world-leading surgeons to reflect the considerable advances made in the surgical
management of HPB disorders since the highly successful first edition.
This new edition includes:

A comprehensive section on anatomy, imaging, and surgical technique


Over 20 new chapters, including a complete account of pediatric HPB disorders
Almost 300 high-resolution images, many in full color
Surgical Management of Hepatobiliary and Pancreatic Disorders, Second Edition,
comprehensively covers the full spectrum of common HPB diseases and associated
surgical techniques to assist not only the general surgeon in regular practice,
but also surgical trainees and those in related specialties of oncology, radiology,
gastroenterology, and anesthesia.

About the Editors


Graeme j. Poston, MS, FRCS (Eng), FRCS (Ed), is Director of Surgery and Hepatobiliary
Surgeon, University Hospital Aintree, Liverpool, UK. He is the President of the Association
of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS), PresidentElect of the European Society of Surgical Oncology (ESSO), Past President of the British
Association of Surgical Oncology (BASO), and author of numerous publications and
national/international guidelines relating to the practice of HPB surgery.
Michael DAngelica, MD, is an Associate Attending at Memorial Sloan-Kettering
Cancer Center and an Associate Professor at Cornell University/Weill Medical Center.
He is currently the Program Chairman of the American Hepato-Pancreato-Biliary
Association and a writing member of the National Comprehensive Cancer Network
(NCCN) practice guidelines for hepatobiliary malignancy.
Ren Adam, MD, PHD, is Hepatobiliary Surgeon and Professor of Surgery, Hpital Paul
Brousse, Universit Paris-Sud, Villejuif, France.

This book
demonstrates the
wisdom of the
new knowledge
and technical skills
of these diverse
disciplines where
cooperative efforts
contribute toward
the benefit of the
patients with HPB
disorders.
Also Available
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and Luigi Bolondi
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e-ISBN: 9780203092880

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and Rectal Surgery
Edited by Charles B. Whitlow, David E. Beck, David A.
Margolin, Terry C. Hicks and Alan E. Timmcke
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e-ISBN: 9781420071535

Textbook of Surgical Oncology


Edited by Graeme J. Poston, R. Daniel Beauchamp,
and Theo J. M. Rogers
ISBN: 9781841845074
e-ISBN: 9780203003220

Surgical Management of Hepatobiliary


and Pancreatic Disorders

An in-depth coverage of benign and malignant disorders of the liver, pancreas, and
bile ducts and gallbladder

With a Foreword by
Yuji Nimura, MD, President
of the Aichi Cancer Center,
Japan, and Past President
of the IHPBA

Poston DAngelica Adam

Surgical Management of Hepatobiliary


and Pancreatic Disorders

Second
Edition

Telephone House, 69-77 Paul Street, London EC2A 4LQ, UK


52 Vanderbilt Avenue, New York, NY 10017, USA

www.informahealthcare.com

Surgical
Management of

Hepatobiliary
and Pancreatic
Disorders
Second Edition

Edited by

Graeme J. Poston
Michael DAngelica
Ren Adam

Surgical Management of Hepatobiliary


and Pancreatic Disorders

Surgical Management of Hepatobiliary


and Pancreatic Disorders
Second Edition
Edited by
Graeme J. Poston MS, FRCS (ENG), FRCS (ED)
Centre for Digestive Diseases
University Hospital Aintree
and
Department of Surgery
The Royal Liverpool University Hospitals
Liverpool, UK

Michael DAngelica MD
Weill Medical College of Cornell University
and
Memorial Sloan-Kettering Cancer Center
New York, New York, USA
and

Ren Adam MD, PHD


AP-HP Hpital Paul Brousse
Centre Hpato-Biliaire
Villejuif, France

First published in 2003 by M. Dunitz Ltd, United Kingdom


This edition published in 2010 by Informa Healthcare, Telephone House, 69-77 Paul Street, London EC2A 4LQ, UK.
Simultaneously published in the USA by Informa Healthcare, 52 Vanderbilt Avenue, 7th floor, New York, NY 10017, USA.
2011 Informa UK Ltd, except as otherwise indicated.
No claim to original U.S. Government works.
Reprinted material is quoted with permission. Although every effort has been made to ensure that all owners of copyright material
have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions
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Printed and bound in the United Kingdom

Contents
List of contributors
Foreword
Preface
I

vii
x
xi

1
17

Margo Shoup and Jason W. Smith

3 Hepatic resection

166

C. Kahlert, R. DeMatteo, and J. Weitz

Robert Jones and Graeme J. Poston

2 Anatomy of the pancreas

154

Kaori Ito

17 Noncolorectal, nonneuroendocrine metastases

ANATOMY/IMAGING/SURGICAL TECHNIQUE
1 Surgical anatomy of the liver and bile ducts

16 Management of neuroendocrine tumor


hepatic metastasis

18 Chemotherapy-associated hepatotoxicity

19 Thermal ablation of liver metastases


24

173

Martin Palavecino, Daria Zorzi,


and Jean-Nicolas Vauthey

180

Samir Pathak and Graeme J. Poston

Ajay V. Maker and Michael DAngelica

4 Ultrasound for HPB disorders

36

20 Resection for hepatocellular carcinoma

Duan Li and Lucy Hann

5 Liver surgery in elderly patients

46

Rajesh Satchidanand, Stephen W. Fenwick,


and Hassan Z. Malik

53

21 Treatment of laparoscopically discovered


gallbladder cancer

Gerardo Sarno and Graeme J. Poston

6 Small solitary hepatic metastases: when and how?


David L. Bartlett and Yuman Fong

7 Managing complications of hepatectomy

63
73

Thilo Hackert, Moritz Wente, and Markus W. Bchler

9 Surgical complications of pancreatectomy

81

Steven C. Katz and Murray F. Brennan

10 Laparoscopy in HPB surgery

89

Nicholas ORourke and Richard Bryant

11 Cross-sectional imaging for HPB disorders


(MRI and CT)

192

197

Jason K. Sicklick, David L. Bartlett, and Yuman Fong

Fenella K. S. Welsh, Timothy G. John, and Myrddin Rees

8 Pancreatic resection

ii. Primary

22 Liver transplantation for HCC: Asian perspectives


Shin Hwang, Sung-Gyu Lee, Vanessa de Villa,
and Chung Mao Lo

23 Non-surgical treatment of hepatocellular


carcinoma

Lawrence H. Schwartz

216

Ghassan K. Abou-Alfa and Karen T. Brown

24 Resection of intrahepatic cholangiocarcinoma

223

Junichi Arita, Norihiro Kokudo, and Masatoshi Makuuchi

25 Transplantation for hilar cholangiocarcinoma


100

208

229

Julie K. Heimbach, Charles B. Rosen,


and David M. Nagorney

26 Rare vascular liver tumors

233

Jan P. Lerut, Eliano Bonaccorsi-Riani,


Giuseppe Orlando, Vincent Karam, Ren Adam,
and the ELITA-ELTR Registry

II LIVER
A. Malignant
i. Metastases
12 Liver metastases: detection and imaging

109

Valrie Vilgrain, Ludovic Trinquart, and Bernard Van Beers

13 Surgery for metastatic colorectal cancer

27 Management of recurrent pyogenic cholangitis


118

Ren Adam and E. Hoti

14 Chemotherapy for metastatic colorectal cancer

135

Gerardo Sarno and Graeme J. Poston

242

W. Y. Lau and C. K. Leow

28 Liver abscess: amebic, pyogenic, and fungal

Derek G. Power and Nancy E. Kemeny

15 Multimodal approaches to the management


of colorectal liver metastases

B. Benign

253

Purvi Y. Parikh and Henry A. Pitt

29 Benign solid tumors of the adult liver

261

Mark Duxbury and O. James Garden

148

30 Liver trauma

271

Timothy G. John, Myrddin Rees, and Fenella K. Welsh

CONTENTS
31 Portal hypertension

280

Michael D. Johnson and J. Michael Henderson

32 Liver transplantation for acute and chronic


liver failure

A. Malignant
288

Vincent Kah Hume Wong and J. Peter A. Lodge

33 Benign cystic disease of the liver

301

Stephen W. Fenwick and Dowmitra Dasgupta

34 Management of hydatid disease of the liver

308

Adriano Tocchi

35 Surgical management of primary sclerosing


cholangitis

324

401

Michael G. House and Keith D. Lillemoe

44 Cystic tumors of the pancreas

407

Peter J. Allen and Murray F. Brennan

414

Stephen N. Hochwald and Kevin Conlon

432

B. Benign
329

Hiromichi Ito and William R. Jarnagin

47 Acute pancreatitis

439

C. Ross Carter, A. Peter Wysocki, and Colin J. McKay

333

Yuji Nimura

48 Chronic pancreatitis

451

Jakob R. Izbicki, Oliver Mann, Asad Kutup,


and Kai A. Bachmann

343

Nick Stern and Richard Sturgess

49 Pancreatic injury

463

Demetrios Demetriades, Beat Schnriger,


and Galinos Barmparas

B. Benign
39 Choledochal cyst detected in adulthood

43 Palliation of pancreas cancer

Jooyeun Chung, Lisa J. Harris, Hamid Abdollahi,


and Charles J. Yeo

A. Malignant

38 Endoscopic management of malignant


biliary obstruction

380

Andr L. Mihaljevic, Jrg Kleeff, and Helmut Friess

46 Rare tumors of the pancreas

III BILE DUCTS AND GALLBLADDER

37 Extrahepatic cholangiocarcinoma

42 Adenocarcinoma of the pancreas

45 Neuroendocrine pancreatic tumors

Jason A. Breaux and Steven A. Ahrendt

36 Management of advanced gallbladder cancer

IV PANCREAS

50 Pancreas transplantation
354

470

Khalid Khawaja

Bilal Al-Sarireh and Hassan Malik

40 Bile duct injuries and benign biliary strictures

360

Steven M. Strasberg

41 Gallstones and common bile duct


stonessurgical and non-surgical approaches
Matthew P. Dearing and Michael Rhodes

vi

V PEDIATRIC HPB DISORDERS


51 Pediatric HPB disorders

373

478

Maureen McEvoy and Michael P. La Quaglia

Index

489

List of contributors
Ghassan K. Abou-Alfa MD
Assistant Attending, Memorial Sloan-Kettering Cancer Center, and
Assistant Professor, Weill Medical College at Cornell University,
New York, New York, USA
Hamid Abdollahi MD
Senior Resident (General Surgery), Department of Surgery, Thomas
Jefferson University, Philadelphia, Pennsylvania, USA
Ren Adam MD, PhD
AP-HP Hpital Paul Brousse, Centre Hpato-Biliaire, Inserm,
Unit 785, and Universit Paris-Sud, UMR-S 785, Villejuif, France
Steven A. Ahrendt MD
Associate Professor of Surgery, University of Pittsburgh
Medical Center, UPMC Passavant Cancer Center, Pittsburgh,
Pennsylvania, USA
Peter J. Allen MD
Department of Surgery, Memorial Sloan-Kettering Cancer Center,
New York, New York, USA
Bilal Al-Sarireh MBBCh, FRS, PhD
Consultant Hepatopancreatobiliary and Laparoscopic Surgeon,
Swansea University, and Department of Surgery, Morristown Hospital,
Swansea, UK
Junichi Arita MD, PhD
Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and
Transplantation Division, Department of Surgery, Graduate School of
Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Kai A. Bachmann
Department of General, Visceral and Thoracic Surgery, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany
Galinos Barmparas
Division of Trauma and Surgical Critical Care, University of Southern
California, Los Angeles, California, USA
David L. Bartlett
Department of Surgery, University of Pittsburgh, Pittsburgh,
Pennsylvania, and National Cancer Institute, National Institutes
of Health, Bethesda, Maryland, USA
Eliano Bonaccorsi-Riani
Th. STARZL Abdominal Transplant Unit, Cliniques Universitaires
St Luc Universit catholique de Louvain, Department of Abdominal
and Transplantation Surgery, Brussels, Belgium
Jason A. Breaux MD
Surgical Oncology Fellow, University of Pittsburgh Medical Center,
UPMC Cancer Pavilion, Pittsburgh, Pennsylvania, USA
Murray F. Brennan
Benno C. Schmidt Clinical Chair in Oncology, Department of Surgery,
Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Karen T. Brown MD
Attending Radiologist, Memorial Sloan-Kettering Cancer Center, and
Professor of Clinical Radiology, Weill Medical College at Cornell
University, New York, New York, USA

C. Ross Carter
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow,
Scotland, UK
Jooyeun Chung MD
Department of Surgery, The Methodist Hospital, Houston, Texas, USA
Kevin Conlon
Professor of Surgery, University of Dublin, Trinity College Dublin, and
Professorial Surgical Unit, Education Centre, AMNCH, Dublin,
Ireland
Michael DAngelica MD
Weill Medical College of Cornell University and Memorial
Sloan-Kettering Cancer Center, New York, New York, USA
Dowmitra Dasgupta MD, FRCS
Consultant Hepato-Pancreatico-Biliary Surgeon, Department of Upper
GI Surgery, Castle Hill Hospital, Cottingham, UK
Matthew P. Dearing
Department of Surgery, Norfolk & Norwich University Hospital,
Norwich, UK
R. DeMatteo
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New
York, New York, USA
Demetrios Demetriades
Division of Trauma and Surgical Critical Care, University of Southern
California, Los Angeles, California, USA
Mark Duxbury
Clinical Surgery, University of Edinburgh Royal Infirmary,
Edinburgh, UK
Stephen W. Fenwick MD, FRCS
Consultant Hepatobiliary Surgeon, North Western Hepatobiliary Unit,
University Hospital Aintree, Lower Lane, Liverpool, UK
Yuman Fong MD
Hepatobiliary Service, Department of Surgery, Memorial
Sloan-Kettering Cancer Center, New York, New York, USA
Helmut Friess
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar,
Technische Universitt Mnchen, Munich, Germany
O. James Garden
Regius Professor of Clinical Surgery, Clinical and Surgical Sciences
(Surgery), University of Edinburgh, Royal Infirmary, Edinburgh, UK
Thilo Hackert
Department of Surgery, University of Heidelberg, Heidelberg, Germany
Lisa J. Harris MD
Senior Resident (General Surgery), Department of Surgery, Thomas
Jefferson University, Philadelphia, Pennsylvania, USA
J. Michael Henderson
Chief Quality Officer, Cleveland Clinic, Cleveland, Ohio, USA

Richard Bryant MBBS, FRACS


Royal Brisbane Hospital, Brisbane, Queensland, Australia

Stephen N. Hochwald MD
Chief, Division of Surgical Oncology, University of Florida, Gainesville,
Florida, USA

Markus W. Bchler
Department of General Surgery, University of Heidelberg, Heidelberg,
Germany

Michael G. House MD
Assistant Professor, Department of Surgery, Indiana University School
of Medicine, Indianapolis, Indiana, USA

vii

LIST OF CONTRIBUTORS
Lucy Hann MD
Professor of Radiology, Weill Cornell Medical Center, and Director of
Ultrasound Memorial Sloan-Kettering Cancer Center, New York,
New York, USA
Julie K. Heimbach
Mayo Clinic, Rochester, Minnesota, USA
Steven N. Hochwald
University of Florida Medical School, Box 100286, Gainesville,
FL 326100286, USA
E. Hoti
AP-HP Hpital Paul Brousse, Centre Hpato-Biliaire, Villejuif, France,
and Liver Transplant Unit, Saint Vincents University Hospital,
Dublin, Ireland
Shin Hwang
Professor, Division of Hepatobiliary Surgery and Liver
Transplantation, Department of Surgery, University of Ulsan College
of Medicine, Seoul, Korea
Hiromichi Ito MD
Department of Surgery, Michigan State University,
Lansing, Michigan, USA
Kaori Ito MD
Department of Surgery, Michigan State University, Lansing, Michigan,
USA
Jakob R. Izbicki FACS
Department of General, Visceral and Thoracic Surgery, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany
William R. Jarnagin MD
Hepatobiliary Service, Department of Surgery, Memorial
Sloan-Kettering Cancer Center, New York, New York, USA
Timothy G. John MD, FRCSEd (Gen)
Hepatobiliary Unit, Basingstoke and North Hampshire Hospitals NHS
Foundation Trust, Basingstoke, UK
Michael D. Johnson MD
Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
Robert Jones MB, ChB, MRCS
Clinical Fellow, North Western Hepatobiliary Centre, Aintree
University Hospital, Liverpool, UK
C. Kahlert
Department of Surgery, University of Heidelberg, Heidelberg, Germany
Vincent Karam
Centre Hpatobiliaire, Hpital Paul Brousse, Villejuif, France
Steven C. Katz MD
Director of Surgical Immunotherapy, Roger Williams Medical Center,
Providence, Rhode Island, USA
Khalid Khwaja MD
Director of Kidney and Pancreas Transplantation, Senior
Staff Surgeon, Lahey Clinic, Burlington, Massachusetts, USA
Nancy E. Kemeny MD
Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Jrg Kleeff
Department of Surgery, Klinikum rechts der Isar, Technische
Universitt Mnchen, Munich, Germany
Norihiro Kokudo MD, PhD
Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and
Transplantation Division, Department of Surgery, Graduate School of
Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Asad Kutup
Department of General, Visceral and Thoracic Surgery, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany

viii

W. Y. Lau
Faculty of Medicine, The Chinese University of Hong Kong, Prince of
Wales Hospital, Shatin, New Territories, Hong Kong, SAR
C. K. Leow
Mount Elizabeth Medical Centre, Singapore, Singapore
Keith D. Lillemoe MD
Jay L. Grosfeld Professor and Chairman, Department of Surgery,
Indiana University School of Medicine, Indianapolis, Indiana, USA
Sung-Gyu Lee
Professor, Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Ulsan College of Medicine,
Seoul, Korea
Michael P. La Quaglia MD
Department of Surgery, Pediatric Surgery Service, Memorial
Sloan-Kettering Cancer Center, New York, New York, USA
Jan P. Lerut MD, PhD, FACS
Th. STARZL Abdominal Transplant Unit, Cliniques Universitaires
St Luc Universit catholique de Louvain, Department of Abdominal
and Transplantation Surgery, Brussels, Belgium
Duan Li MD
Assistant Attending Radiologist, Memorial Sloan-Kettering Cancer
Center, New York, New York, USA
Chung Mao Lo
Professor, Department of Surgery, Queen Mary Hospital,
The University of Hong Kong, Hong Kong, China
J. Peter A. Lodge MD, FRCS
Professor and Clinical Director, HPB & Transplant Unit, St. James
University Hospital, Leeds, UK
Ajay V. Maker MD
Director of Surgical Oncology, Creticos Cancer CenterAdvocate
Illinois Masonic Medical Center; Departments of Surgery and
Microbiology/Immunology, University of Illinois at Chicago, Chicago,
Illinois, USA
Masatoshi Makuuchi MD, PhD
Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and
Transplantation Division, Department of Surgery, Graduate School of
Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Hassan Malik MD, FRCS
Hepatobiliary Unit, Department of Surgery, University Hospital
Aintree, Liverpool, UK
Oliver Mann
Department of General, Visceral and Thoracic Surgery, University
Medical Center Hamburg-Eppendorf, Hamburg, Germany
Maureen McEvoy MD
Department of Surgery, Pediatric Surgery Service, Memorial
Sloan-Kettering Cancer Center, New York, New York, USA
Colin J. McKay
West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow,
Scotland, UK
Andr L. Mihaljevic
Department of Surgery, Klinikum rechts der Isar, Technische
Universitt Mnchen, Munich, Germany
David M. Nagorney
Mayo Clinic, Rochester, Minnesota, USA
Yuji Nimura MD
President, Aichi Cancer Center, Chikusaku, Nagoya, Japan
Giuseppe Orlando
Th. STARZL Abdominal Transplant Unit, Cliniques Universitaires St
Luc Universit catholique de Louvain, Department of Abdominal and
Transplantation Surgery, Brussels, Belgium

LIST OF CONTRIBUTORS
Nicholas ORourke MBBS, FRACS
Royal Brisbane Hospital, Brisbane, Queensland, Australia
Martin Palavecino MD
Department of Surgical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, Texas, USA
Purvi Y. Parikh MD
Department of Surgery, Albany Medical College, Albany, New York,
USA
Samir Pathak MD, ChB, MSC, MRCS
Clinical Fellow, North Western Hepatobiliary Centre, Aintree
University Hospital, Liverpool, UK
Henry A. Pitt MD
Indiana University, Indianapolis, Indiana, USA
Graeme J. Poston MS, FRCS (Eng), FRCS (Ed)
Centre for Digestive Diseases, University Hospital Aintree, and
Department of Surgery, The Royal Liverpool University Hospitals,
Liverpool, UK
Derek G. Power MD
Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Myrddin Rees MS, FRCS, FRCS (Ed)
Hepatobiliary Unit, Basingstoke and North Hampshire Hospitals NHS
Foundation Trust, Basingstoke, UK
Michael Rhodes
Department of Surgery, Norfolk & Norwich University Hospital,
Norwich, UK
Charles B. Rosen
Mayo Clinic, Rochester, Minnesota, USA

Jason W. Smith MD
Chief Resident, Department of Surgery, Loyola University Medical
Center, Maywood, Illinois, USA
Nick Stern
Consultant Gastroenterologist, Digestive Diseases Department,
University Hospital Aintree, Liverpool, UK
Richard Sturgess
Consultant Gastroenterologist and Clinical Director, Digestive Diseases
Department, University Hospital Aintree, Liverpool, UK
Adriano Tocchi
Head of 1st Department of Surgery and Chief of the Gastro-intestinal
and Hepato-biliary Surgical Service, University of Rome Sapienza
Medical School, Rome, Italy
Ludovic Trinquart
Department of Radiology, Assistance-Publique Hpitaux de Paris,
Hpital Beaujon, Clichy, France
Bernard Van Beers
Department of Radiology, Assistance-Publique Hpitaux de Paris,
Hpital Beaujon, Clichy; Universit Paris; and Centre de recherche
biomdicale Bichat-Beaujon, Paris, France
Jean-Nicolas Vauthey MD
Department of Surgical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, Texas, USA
Valrie Vilgrain
Department of Radiology, Assistance-Publique Hpitaux de Paris,
Hpital Beaujon, Clichy; Universit Paris; and Centre de recherche
biomdicale Bichat-Beaujon, Paris, France

Gerardo Sarno MD
Clinical Fellow, North Western Hepatobiliary Centre, Aintree
University Hospital, Liverpool, UK

Vanessa de Villa
Assistant Professor, Department of Surgery, Queen Mary Hospital,
The University of Hong Kong, Hong Kong, China

Rajesh Satchidanand MD, FRCS


Clinical Fellow, North Western Hepatobiliary Centre, Aintree
University Hospital, Liverpool, UK

J. Weitz MD
Department of Surgery, University of Heidelberg, Heidelberg, Germany

Beat Schnriger
Division of Trauma and Surgical Critical Care, University of Southern
California, Los Angeles, California, USA
Lawrence H. Schwartz
Department of Radiology, Columbia University College of Physicians and
Surgeons, and Radiologist-in-Chief, New YorkPresbyterian Hospital/
Columbia University Medical Center, New York, New York, USA
Margo Shoup MD, FACS
Chief, Division of Surgical Oncology, Department of Surgery, Loyola
University Medical Center, Maywood, Illinois, USA
Jason K. Sicklick
Department of Surgery, Memorial Sloan-Kettering Cancer Center,
New York, New York, USA
Steven M. Strasberg MD, FRCS(C), FACS, FRCS (Ed)
Pruett Professor of Surgery and Head Hepato-Pancreato-Biliary and
Gastrointestinal Surgery, Washington University in Saint Louis and
Barnes-Jewish Hospital, Saint Louis, Missouri, USA

Fenella K. S. Welsh MA, MD, FRCS (Gen Surg)


Hepatobiliary Unit, Basingstoke and North Hampshire Hospitals NHS
Foundation Trust, Basingstoke, UK
Moritz Wente
Department of Surgery, University of Heidelberg, Heidelberg, Germany
Vincent Kah Hume Wong MBCB, MRCS
Research Fellow in Hepatopancreatobiliary & Transplant Surgery, HPB
& Transplant Unit, St. James University Hospital, Leeds, UK
A. Peter Wysocki
Department of Surgery, Logan Hospital, Meadowbrook, Queensland,
Australia
Charles J. Yeo MD
The Samuel D. Gross Professor and Chair, Department of Surgery,
Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Daria Zorzi MD
Department of Surgical Oncology, The University of Texas M. D.
Anderson Cancer Center, Houston, Texas, USA

ix

Foreword
As recent progress in hepato-pancreato-biliary (HPB) surgery
has been evident since the first edition of this book was published eight years ago, Dr. Graeme Poston, Dr. Mike
DAngelica, and Dr. Ren Adam, internationally recognized
authorities in HPB surgery, have attempted to rewrite the second edition, joined by selected numerous worldwide specialists renowned as expert authors in each field to present a
current view of the surgical and non-surgical management of
benign and malignant HPB disorders.
This book demonstrates the wisdom of the new knowledge
and technical skills of these diverse disciplines where cooperative

efforts contribute toward the benefit of the patients with HPB


disorders.
The general surgeon will find this volume to be a useful source
of current thoughts on how to manage the diverse HPB diseases.
Yuji Nimura MD
President, Aichi Cancer Center
Professor Emeritus, Nagoya University Graduate
School of Medicine
Past President, International Hepato-Pancreato-Biliary
Association (IHPBA)

Preface
Hepato-pancreato-biliary (HPB) surgery is now firmly
established within the repertoire of modern general surgery.
Indeed, in many major tertiary centers there are now specific
teams for both pancreatic and liver surgery. However, in most
hospitals outside these major centers the day-to-day management and decision-making for patients with these disorders
remains the remit of the general surgeon.
Following the launch of the highly successful first edition of
this book eight years ago there have been considerable
advances in the surgical management of HPB disorders. Many
of these relate to related specialties (radiology, oncology, gastroenterology, and anesthesia) and also directly to surgery
(liver transplantation, caval bypass and replacement, laparoscopic surgery to name but a few). As such the second edition
has been completely rewritten from scratch.
As with the first edition, the purpose of this edition is
twofold. First, it is intended to cover the spectrum of common

HPB diseases that will confront the general surgeon in his or


her regular practice. Second, we hope that this work will be
sufficiently comprehensive to cover the broad spectrum of
HPB surgery for candidates coming to examinations at the
completion of surgical training.
We are indebted to the many international contributors for
their perseverance and patience over the gestation of this project, which is greatly appreciated. Lastly, we are grateful to our
publishers, Informa Healthcare, for their help during the
preparation of this project.
Graeme J. Poston
Michael DAngelica
Ren Adam
September 2010

xi

Surgical anatomy of the liver and bile ducts


Robert Jones and Graeme J. Poston

The success of any surgical intervention on the liver and bile


ducts is totally dependent on a thorough working knowledge
of their anatomy. As the number of patients undergoing hepatobiliary surgery is increasing, good understanding of the
anatomy of this area is increasingly important for any surgeon
with an interest in the gastrointestinal tract. Command of this
anatomy is also essential for the successful interpretation of
functional imaging of hepatobiliary anatomy.
When operating on the liver and biliary tree, the surgeon has
to obey three basic tenets.

Remove all pathologically involved tissue.


Preserve the maximal amount of functioning nonpathological liver tissue.
Perform safe resection, while ensuring adequate
blood supply to the remaining hepatic parenchyma.

Historically, the liver was described according to its morphological appearance (1,2). However, these three tenets have
altered the approach to surgery, and the liver is now considered from a functional and therefore surgical perspective.

morphological anatomy
Historically, when viewed at laparotomy, the liver appears
divided into a larger right lobe, and a smaller left lobe by
the umbilical fissure and falciform ligament (Figs. 1.1 and
1.2) (3). Situated on the inferior surface of the right lobe is the
transverse hilar fissure, which constitutes the posterior limit of
the right lobe. The quadrate lobe was defined as the portion
of the right lobe lying anterior to this transverse hilar fissure
and to the right of the umbilical fissure, its other margin being
defined by the gallbladder fossa. The caudate lobe, which is
anatomically and functionally separate from the rest of the
liver, lies posterior to the hilum, between the portal vein and
the inferior vena cava (IVC) (4).
This historical anatomical approach does not consider the
vasculature or biliary drainage of the liver and is of only limited use when planning surgical resection.

early application of the functional


anatomy
Isolated liver wounds, usually as a result of military action,
had been successfully treated since the early seventeenth
century (5,7), but the first attempt at resection of a liver tumor
was not made until 1886, when the French surgeon Luis
excised a solid liver tumor by ligating and cutting through a
pedunculated left lobe adenoma. Attempts to suture the severed pedicle were unsuccessful, and the stump was returned to
the peritoneal cavity. Not surprisingly, the patient succumbed
some six hours later (8).
In 1888, Rex reported a new arrangement of the right and
left lobes of the liver and further refined our understanding of

lobar anatomy (2). The first successful elective liver resection


was performed two years later by von Langenbuch, who
excised a portion of the left lobe of the liver containing an
adenoma in 1888 (9). He had to reopen the abdomen several
hours after the operation because of reactionary hemorrhage,
but was able to ligate the bleeding vessels and return the oversewn liver to the abdomen.
Two years later in 1890, the Baltimore surgeon McLane
Tiffany reported the successful removal of a benign liver
tumor (10), and the following year Lucke described the
successful resection of a cancerous growth of the liver (11).
Surgery was now becoming a recognized treatment for liver
pathology. Advances in surgery closely mirrored increased
understanding of the functional anatomy of the liver (1214).
The first attempt to define the functional anatomy of the
liver, which could possibly guide current surgical practice, was
made by Cantlie in 1898, while working in Hong Kong. He dissected the livers of executed prisoners (15) and making vascular casts, he demonstrated that the main division between the
right and left lobe in fact extended from approximately the
gallbladder fossa, to the right side of the IVC, posterosuperiorly. Cantlies line, therefore, follow a line drawn from the gallbladder fossa, along the middle hepatic vein, to the IVC
(Figs. 1.2 and 1.3) (3). In 1911, Wendel reported the first case
of right lobectomy for a primary tumor (16), however this
procedure did not follow the precise anatomical plane
described by Cantlie.
In 1939, while working in Paris, the Vietnamese surgeon Ton
That Tung described the venous drainage of the liver in relation to the true lobar anatomy (Fig. 1.4) (17). The first anatomically correct description of a left lateral segmentectomy
was made by Raven in 1948 while resecting metastatic colon
cancer (18). Four years later, Lortat-Jacob and Robert finally
described a similar approach to the true right hepatic lobectomy, based on the anatomical principles described by Cantlie
(Fig. 1.6) (19).
Healey and Schroy were the first to demonstrate in 1953 that
the right lobe was further divided into an anterior and a posterior sector (20). They also showed that the left lobe was
divided into a medial and lateral sector by the line of the falciform ligament and umbilical vein (Fig. 1.5). Understanding of
the functional anatomy of the liver continued to develop, and
in 1957, Goldsmith and Woodburne described a number of
anatomical planes through the liver parenchyma that followed
this functional anatomy. Their paper finally defined true right
lobectomy (right hepatectomy), left lobectomy (left hepatectomy), and left lateral segmentectomy (Fig. 1.6) (21).

appreciation of segmental anatomy


Probably the most important anatomical contribution to
modern liver surgery comes from the work of the late Claude

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


IVC

Middle hepatic vein lying


among Cantlie's line

IVC

Left lobe
Right lobe

IVC

IVC Right free border of


lesser omentum

Cantlie's line

Figure 1.1 Morphological anatomy.

Gallbladder

Figure 1.3 Cantlies line.

Umbilical
fissure

Cantlie's line

Gallbladder

Quadrate lobe

supply (inflow and outflow), and therefore viability, to the


remaining hepatic parenchyma.
The description of Couinaud is the most complete and
exact, and also the most useful for the operating surgeon, and
therefore it is this description that will be used throughout
this book.

segmental anatomy of the liver


Transverse
hilar fissure
Gastrohepatic
omentum

Common bile duct,


hepatic artery
and portal vein

IVC Caudate lobe

Figure 1.2 Anatomical features.

Couinaud, who in 1957 produced a huge number of vasculobiliary casts of the liver (23,24). Couinaud was able to demonstrate that the liver appeared to consist of eight anatomical
segments, each of which could potentially be separately resected
without affecting the physiological viability of the other segments. Couinaud redefined the caudate lobe as segment 1 and
Goldsmith and Woodburnes left lobe as segments 2 and 3. The
quadrate lobe was termed segment 4, and more recently has
been subdivided by further studies of its portal blood supply
into 4A (superiorly) and 4B (inferiorly). The right liver consists
of segments 5 (anteroinferiorly), 6 (posteroinferiorly), 7 (posterosuperiorly), and 8 (anterosuperiorly) (Fig. 1.7). Couinaud
later suggested a further clarification, in which the caudate lobe
to the left of the IVC remained segment 1, with that to the right
being redefined as segment 9 (25).
Resections based on these anatomical segments enable the
surgeon to safely operate following the three central tenets
described above; remove all pathologically involved tissue,
preserve the maximal amount of nonpathological liver tissue,
and perform safe resection, while ensuring an adequate blood

These anatomical studies of the functional anatomy of the


liver allow us to define hepatic segments based upon both
the distribution of the portal pedicles and the drainage of the
hepatic veins (Fig. 1.5). The three main hepatic veins (right,
middle, and left) divide the liver into four sectors, each of
which receives a portal pedicle containing branches of the
hepatic artery, hepatic duct, and portal vein; thus producing
an alternation between hepatic veins and portal pedicles.
These four sectors, demarcated by the hepatic veins, are the
portal sectors, each sector therefore receiving an independent
portal supply. For the same reason, the scissurae containing
the hepatic veins are termed the portal scissurae while the scissurae containing portal pedicles are the hepatic scissurae
(Fig. 1.5). Thus, the liver is divided by the main portal scissura
along the line of the middle hepatic vein into two discrete
hemilivers, along the line previously described by Cantlie (15).
We therefore refer to these hemilivers as right and left livers,
rather than right and left lobes, to avoid confusion with the
anatomical lobes, particularly since there is no visible surface
marking that permits individualization of the true lobes.
As described by Cantlie, the main portal scissura runs posteriorly from the middle of the gallbladder fossa to the right side
of the IVC (Fig. 1.5). Therefore, the right and left livers, demarcated by the main portal scissura, are independent in terms of
their portal and arterial vascularization and their biliary
drainage.
These right and left livers are both further divided into two
by the other two portal scissurae, delineated by the right and
left hepatic veins. Goldsmith and Woodburne refer to these
further divisions as segments (21), but for the rest of this
book, we will use the more generally accepted nomenclature of
Couinaud, which refers to these divisions as sectors (23). The

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS


Right liver

Left liver

IVC

Middle hepatic vein


(usually enters left vein
before IVC)

Left heptic vein

Right
hepatic vein

Caudate hepatic veins


(variable)

Right inferior
hepatic vein
(variable)
IVC
Gallbladder, note that the middle vein
may lie superficially in the gallbladder fossa
Figure 1.4 Venous drainage of the liver.

IVC

Middle hepatic vein in


main portal scissura
following Cantlie's line

Right hepatic
vein in right
portal scissura

Left hepatic vein


in left portal
scissura
Lateral
segment of
left lobe

3
1
4

Right
posterior
sector

Falciform ligament
6

5
Medial segment of left lobe
Right anterior sector
Right liver

Portal vein
Left liver

Figure 1.5 Functional sectoral anatomy and relationship to hepatic scissurae.

right liver is divided by the right portal scissura (right portal


vein) into an anteromedial (or anterior) sector containing
segments 5 inferiorly and 8 superiorly, and a posterolateral (or
posterior) sector containing segments 6 inferiorly and 7 superiorly (Fig. 1.5). When the liver lies in its normal position
within the upper abdominal cavity, the right posterolateral
sector lies directly behind the right anteromedial sector, and
this scissura is therefore almost in the coronal plane. Therefore
in the clinical setting (particularly when imaging the liver), it
is better to speak of these anterior and posterior sectors
(Fig. 1.5). The exact location of the right portal scissura is
imprecise, because it has no external landmarks. According to
Couinaud (23), it extends from the edge of the liver at the middle point between the back of the liver and the right side of the

gallbladder bed along the right hepatic vein posteriorly to the


confluence of the right hepatic vein and the IVC (2628).
The venous drainage of the right liver is variable in that, in
addition to the right and middle hepatic veins, there are often
a number of smaller hepatic veins draining directly into the
IVC from segments 6 and 7. Not infrequently (6368%) segment 6 drains directly into the IVC through a distinct inferior
right hepatic vein, larger than these other venous tributaries to
the IVC, which can be a significant bonus in the preservation
of residual hepatic function when undertaking extended left
hepatectomies (Fig. 1.4) (29,30).
The left portal scissura, along the left hepatic vein, divides
the left liver into two sectors: an anterior sector containing
segments 3 and 4 and a posterior sector containing segment 2

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

(C)

(D)

(E)
Figure 1.6 Formal hepatectomies: (A) right hepatectomy; (B) left hepatectomy; (C) left lateral segmentectomy; (D) extended left hepatectomy; (E) extended right
hepatectomy.

8
8

3
1
5

4
5

6
6

(A)

(B)

Figure 1.7 Functional division of the liver and of the liver segments according to Couinauds nomenclature (A) as seen in the patient and (B) in the ex vivo position.

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS


(Fig. 1.5). It is important to note that the left portal scissura
does not follow the umbilical fissure; this portal scissura
contains a hepatic vein and the umbilical fissure contains
a portal pedicle. Therefore the left portal scissura lies posterior to the ligamentum teres, inside the left lobe of the liver
(Fig. 1.5).
The middle hepatic vein (defining the main portal scissura)
usually enters the left hepatic vein some 1 to 2 cm before the
left hepatic vein joins the IVC (Fig. 1.4) (30). Occasionally the
middle and left hepatic veins enter the IVC separately, and in 2
out of 34 of Couinauds casts, the middle vein and left veins
joined at more than 2.5 cm from the IVC (30). Such an anomaly must be detected and excluded during isolated resection of
segment 4, since if it is not seen, and the last 2 cm of the left
vein is damaged, segments 2 and 3 will be needlessly sacrificed
(and in the case of extended right hepatectomy, threaten future
remnant liver viability).
The caudate lobe (segments 1 and 9) is the dorsal portion of
the liver, lying posteriorly and surrounding the retrohepatic
IVC. It lies directly between the portal vein (anteriorly) and
the IVC (posteriorly). The main bulk of the caudate lobe lies to
the left of the IVC, with its left and inferior margins being free
in the lesser omental bursa (Fig. 1.2). The gastrohepatic (lesser)
omentum separates the caudate from segments 2 and 3 of the
left liver. The left portion of the caudate lobe lies inferior to the
right between the left portal vein and the IVC, as the caudate
process. This process then fuses inferiorly with segment 6 of
the right liver. The amount of caudate lobe that lies on the
right side is variable, but usually small. The anterior surface of
the caudate lobe lies within the hepatic parenchyma against
the posterior intrahepatic surface of segment 4, demarcated by
an oblique plane slanting from the left portal vein to the left
hepatic vein.
The caudate lobe must be considered functionally as an isolated autonomous segment, since its vascularization is independent of the portal division and of the three main hepatic
veins. It receives a variable arterial and portal blood supply
from both the right and left portal structures, although the
right caudate lobe consistently receives an arterial supply from
the right posterior artery. Biliary drainage is likewise into both
the right and left hepatic ducts. However, the left dorsal duct
can also join the segment 2 duct. The small hepatic veins of the
caudate lobe drain directly into the IVC. This independent
functional isolation of the caudate lobe is clinically important
in BuddChiari syndrome; if all three main hepatic veins are
obliterated, the only functioning hepatic venous drainage is
through the caudate lobe, which therefore undergoes compensatory hyperplasia.

anatomical classification of hepatectomies


Hepatic resections can be classified as anatomical and
nonanatomical. Anatomical hepatectomies (hepatectomies
reglees) are defined by resection of a portion of liver parenchyma defined by the functional anatomy. These resections
are called left or right hepatectomies, sectorectomies, and segmentectomies. Nonanatomical hepatectomies involve resection of a portion of hepatic parenchyma not limited by
anatomical scissurae. Such resections are usually inappropriate,

as they will leave behind devascularized residual liver and will


also probably not adequately excise all the pathologically
involved parenchyma.
The usual anatomical hepatectomies can be considered in
two groups: right and left hepatectomies in which the line of
transection is the main portal scissura separating the right and
left livers along the middle hepatic vein, and right and left
hepatectomies in which the line of transection commences in
the umbilical fissure.
For some time the latter definition, initially proposed by
Goldsmith and Woodburne (21), has been the accepted convention. We would encourage the use of the former definition, as
segment 4 (quadrate lobe) is anatomically part of the left liver
(Fig. 1.9), and this convention was adopted universally at the
2000 Brisbane Congress of the IHPBA (Brisbane Convention),
and will be used hereafter in this book. Using this functional
approach to liver anatomy, we can define numerous potential
liver resections based upon the order (first, second, third) of
the hepatic divisions (main portal scissura, anterior and posterior right portal scissurae, left portal scissura) (28).
With regard to the first order division, right hepatectomy or
hemihepatectomy (removal of the right liver/hemiliver) therefore consists of the resection of segments 5 to 8 (stipulating
segment 1). Left hepatectomy or hemihepatectomy (removal
of the left hemiliver or liver) is the removal of segments 24
(stipulating segment 1) (Fig. 1.6). In certain pathologies
(multiple liver metastases or large tumors transgressing the
main portal scissura) hepatectomies can be extended to
include adjacent segments and sectors of the other liver. Therefore extended right hepatectomy (right trisegmentectomy or
extended right hemihepatectomy) will also include resection
of segment 4 (stipulating segment 1), taking portal structures to the right of the falciform ligament (Fig. 1.6). Similarly,
extended left hepatectomy (left trisegmentectomy or extended
left hemihepatectomy) would include resection of segments 5
and 8 en bloc with segments 2 to 4 (stipulating segment 1)
(Fig. 1.6).
When discussing second order divisions, individual sectors
can be resected in isolation or in adjacent pairs depending
upon the distribution of pathology. Therefore right anterior
sectionectomy refers to the en bloc resection of segments 5
and 8 (between the main portal scissura (middle hepatic vein)
and right portal scissura (right portal vein) on their pedicle of
the anterior division of the right portal vein). Right posterior
sectionectomy (previously referred to as right posterior or lateral sectorectomy) is the contiguous resection of segments 6
and 7, posterior to the right portal scissura (on the pedicle of
the posterior division of the right portal vein) (Fig. 1.8). On
the left side, isolated excision of segment 4 can be described as
left median sectionectomy, although it is also legitimate to
refer to it as resection segment 4 or segmentectomy 4.
One area of confusion in these definitions of hepatectomies
comes in the simultaneous resection of segments 2 and 3
(Fig. 1.10). Goldsmith and Woodburne originally described
this procedure as a left hepatic lobectomy (21). Describing this
as left lateral segmentectomy is technically wrong since the
true left lateral segment (and sector) comprises no more than
segment 2 (excision of which in isolation can therefore be

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


described as left lateral or posterior sectorectomy). It is now
accepted convention that resection of segments 2 and 3 is
regarded as a left lateral sectionectomy (but can also legitimately be referred to as bisegmentectomy 23).
With regard to the third order divisions, resection is now at
the level of the individual hepatic segment(s). Therefore these
resections are referred to as segmentectomy (classified
according to the segment being removed: 19). Similarly,
segments 5 and 6 can be resected en bloc (and this used to be
described as a right inferior hepatectomy) and this should now
be described as bisegmentectomy 56. If there is a significant
right inferior hepatic vein draining segments 5 and 6, then
segments 7 and 8 can be resected with the right hepatic vein
(bisegmentectomy 78) (Fig. 1.8).

surgical approach to the caudate lobe


This resection (segmentectomy 1 or 9, or 1 and 9 en bloc) is
initially achieved by dissection of the coronary ligament up to
the right of the IVC, being careful to avoid the right hepatic
vein. The falciform ligament is then dissected to the IVC, the

lesser omentum being incised close to the liver. Opening the


left coronary ligament allows ligation of the inferior phrenic
vein. The caudate veins running directly to the IVC are now
exposed and can be divided between ligatures as they run up
the back of the caudate lobe. After the hilar plate is lowered to
expose the right and left portal pedicles, the portal inflow to
both the right and left caudate segments can be identified,
ligated, and divided. The caudate lobe is now isolated and the
main portal fissure is divided to separate segments 4, 7, and 8.
Note that the caudate segment 1s not defined macroscopically
from segment 6.

the biliary tract


Accurate biliary exposure and precise dissection are the two
most important steps in any biliary operative procedure and
are both totally dependent on a thorough anatomical understanding of these structures. Several authors have described
the anatomy of the biliary tract (17,22,23), but unfortunately
the surgical implications have been incompletely described
and continue to be misunderstood by many surgeons.

(A)

(B)

(C)

(D)

(E)
Figure 1.8 Other hepatic sectorectomies: (A) right posterior sectorectomy; (B) right anterior sectorectomy; (C) left medial sectorectomy (segments 4A and 4B);
(D) right inferior hepatectomy; (E) right superior hepatectomy.

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS

intrahepatic biliary anatomy


The right liver and left liver are respectively drained by the
right and the left hepatic ducts. The caudate lobe (segments 1
and 9) is drained by several ducts joining both the right and
left hepatic ducts (20). The intrahepatic ducts are tributaries
of the corresponding hepatic ducts, which form part of the
major portal tracts invaginating Glissons capsule at the hilus
and penetrating the liver parenchyma (Fig. 1.11). There is variation in the anatomy of all three components of the portal
triad structures (hepatic ducts, hepatic arteries, and portal
vein), but it is the portal vein that shows the least anatomical
variability. In particular, the left portal vein tends to be consistent in location (23). Bile ducts are usually located above the
portal vein whereas the corresponding artery will lie below.
Each branch of the intrahepatic portal vein corresponds to one
or two intrahepatic bile ducts, which converge outside the liver
to form the right and left hepatic ducts, in turn joining to form
the common hepatic duct.
The left hepatic duct drains segments 2, 3, and 4, which constitute the left liver. The duct draining segment 3 is found a little behind the left horn of the umbilical recess, from where it
passes directly posteriorly to join the segment 2 duct to the left

of the main portal branch to segment 2. At this point, the left


branch of the portal vein turns forward and caudally in the
recessus of Rex (23) (Figs. 1.12 and 1.13). As the duct draining
segment 3 begins its posterior course it lies superficially in the
umbilical fissure, often immediately under Glissons capsule. As
such it is usually easily accessible at surgery to allow a biliary
enteric (segment 3 hepaticojejunostomy) anastomosis for biliary drainage if such access is not possible at the porta hepatis.
The left hepatic duct then passes beneath the left liver at the
posterior base of segment 4, lying just above and behind the left
branch of the portal vein. After the left duct crosses the anterior
edge of that vein it joins the right hepatic duct to form the common duct at the hepatic ductal confluence. In this transverse
portion, where it lies below the liver parenchyma, it receives
one to three small branches from segment 4 (23).
The right hepatic duct (Fig. 1.14) drains segments 5 to 8 and
arises from the convergence of the two main sectoral (anterior
5 and 8, and posterior 6 and 7) tributaries. The right posterior
sectoral duct runs almost horizontally (26) and comprises the
confluence of the ducts from segments 6 and 7 (Fig. 1.15). The
right posterior duct joins the right anterior sectoral duct
(formed by the confluence of the ducts from segments 5 and 8)

Figure 1.9 Completion of segment 4 resection with portal bifurcation lying


inferiorly in front of the inferior vena cava.

Figure 1.11 Exposing the hilar plate by raising the inferior surface of segment
4B, thus demonstrating the condensation of Glissons capsule, which will
cover the extra hepatic confluence of the right and left hepatic ducts.

Figure 1.10 Left lateral segmentectomy immediately prior to division of the


portal structure lying inferiorly and the left hepatic vein lying superiorly.

Figure 1.12 Exposing the recessus of Rex by distraction of the falciform ligament to demonstrate the bifurcation of segment 3 and segment 4 bile ducts.

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


4
RPV

RHD
RHA

4
(ant.)
3

CHD

PV

HA

Recessus of Rex

Figure 1.13 Biliary and vascular anatomy of the left liver. Note the position of
segment 3 duct above the corresponding vein and its relationship to the recessus of Rex.

as it descends vertically (26). This right anterior sectoral duct


lies to the left of the right anterior sectoral branch of the intrahepatic portal vein as it ascends within the parenchyma
(Fig. 1.15). The junction of the two main right biliary ducts
usually occurs immediately above the right branch of the portal vein (23). The right hepatic duct is considerably shorter
than its counterpart on the left, which it joins to form the common hepatic duct in front of the right portal vein (Fig. 1.15).
The caudate lobe (segments 1 and 9) has its own separate
biliary drainage. This segment comprises two anatomically
and functionally distinct portions, a caudate lobe proper
(which consists of a right and left part) located at the posterior
aspect of the liver, and a caudate process passing behind the
portal structures to fuse with segment 6 of the right liver. In
nearly half of individuals, three separate bile ducts drain these
distinct parts, while in a quarter of individuals, there is a common biliary duct between the right portion of the caudate lobe
proper and the caudate process, while the left part of the caudate lobe is drained by an independent duct. However, the site
of drainage of these ducts is variable. Most authors advocate
en bloc resection of the caudate lobe during resection of hilar
cholangiocarcinoma (31), since the tumor usually infiltrates
these ducts draining the caudate lobe. Certainly these authors
have demonstrated that in 88% of cases of hilar cholangiocarcinoma coming to resection there is histological evidence of
tumor infiltration of the caudate lobe along these ducts.

extrahepatic biliary anatomy

Figure 1.14 Demonstration of the right hepatic duct lying within the gallbladder fossa.

The detail of this section will be confined to the upper part of


the extrahepatic biliary tree, above the common bile duct,
since the common bile duct is also covered in chapter 2. The
right and left hepatic ducts converge at the right of the hilum
of the liver, anterior to the portal venous bifurcation and overlying the origin of the right portal vein. The biliary confluence

Anterior sectoral duct

5
7
Posterior
sectoral
duct

LHD
LPV
6
LHA
CHD

HA
PV

Figure 1.15 Biliary and vascular anatomy of the right liver. Note the horizontal course of the posterior sectoral duct and the vertical course of the anterior sectoral duct.

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS


is separated from the posterior aspect of the base of segment 4
by a fusion of connective tissue investing from Glissons capsule to form the fibrous hilar plate. This hilar plate has no vascular interposition and, when opened behind the posterior
aspect of the base of segment 4, will display the extrahepatic
confluence of the right and left hepatic ducts (Fig. 1.16).
The main bile duct is divided into its upper part, the common hepatic duct, and lower part, the common bile duct, by
the entry of the cystic duct from the gallbladder. This point of
confluence of hepatic and cystic ducts to form the common
bile duct is widely variable, and any surgeon performing the
operation of cholecystectomy has a duty of care to their patient
to be fully aware of this anatomic variability (lest they mistake
the common bile duct, or less frequently the common or right
hepatic ducts for the cystic duct, resulting in catastrophic consequences for the patient). The main bile duct normally has a
diameter of up to 6 mm and passes downward anterior to the
portal vein in the right free border of the lesser omentum. The
bile duct is closely related to the hepatic artery as it runs
upwards on its left side before dividing into its left and right
branches, the right hepatic artery usually passing posteriorly
to the bile duct. The cystic artery, which usually arises from the
right hepatic artery, crosses the common hepatic duct as frequently anteriorly as it does posteriorly (Figs. 1.17 and 1.18).
Calots triangle was originally defined by the common
hepatic duct lying medially, inferiorly by the cystic duct and
superiorly by the cystic artery (32). However, the usually
accepted surgical definition of this triangle has been modified
to that of the cholecystectomy triangle, which defines the

upper border as the inferior surface of the liver (and therefore


contains the cystic artery) (33). The junction of the cystic duct
and common hepatic duct varies widely and may even occur
behind the pancreas. The retropancreatic portion of the bile
duct approaches the duodenum obliquely, accompanied by
the terminal part of the duct of Wirsung (see chap. 2). These
two ducts join to enter the duodenum through the sphincter
of Oddi at the papilla of Vater (34,35).

gallbladder and cystic duct


The gallbladder lies within the cystic fossa on the underside of
the liver in the main liver scissura, thereby defining the junction between the right and left hemilivers. It is separated from
the hepatic parenchyma by the cystic plate, which is an extension of connective tissue from the hilar plate (described previously). The anatomical relationship of the gallbladder to the
liver ranges from hanging by a loose peritoneal reflection to
being deeply embedded within the liver parenchyma. The gallbladder varies in size and consists of a neck, body, and fundus,
which usually reaches the free edge of the liver, still closely
applied to the cystic plate. Large gallstones impacting within
the neck of the gallbladder may create a Hartmanns pouch
(33), and inflammation secondary to this can obscure the anatomical plane between the gallbladder and the common
hepatic duct (thus obliterating the cholecystectomy triangle).
This degree of inflammation can make dissection during cholecystectomy difficult, increasing the risk of damage to the
common hepatic duct (36). Other structures similarly threatened during this dissection as part of cholecystectomy for

Segment 4
Glisson's
capsule
Lig.teres

RHD
RHA

LPV
LHD
LHA

RPV
Cystic artery
Cystic duct
Gallbladder
CHD

Umbilical
fissure

HA

Line of incision of
hilar plate to expose
left hepatic duct
CBD

Retroduodenal
artery
Gastroduodenal
artery
Splenic
vein

Cystic plate

Hilar plate

Figure 1.16 Demonstration of the relationship between the posterior aspect


of the base of segment 4 and the biliary confluence. Note the extension of Glissons capsule to invest the portal structures at the hilum (hilar plate) and
extending over the hepatic surface of the gallbladder (cystic plate). Exposure
of the extrahepatic left hepatic duct is achieved by incising the hilar plate at the
base of segment 4 medially as far as the umbilical fissure.

Superior mesenteric artery and vein


Figure 1.17 Anterior aspect of biliary anatomy. Note the hepatic duct confluence anterior to the right hepatic artery and origin of the right portal vein.
Note also the course of the cystic artery, arising from the right hepatic artery
and passing posteriorly to the common hepatic duct.

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


chronic cholecystitis include the right hepatic artery (in up to
50% of cholecystectomy bile duct injuries, so rendering the
upper bile duct ischemic with ramifications for the timing of
bile duct repair), the right hepatic duct, and in exceptional circumstances, a low-lying middle hepatic vein lying superficially
just below the gallbladder fossa.

(A)

(B)

(D)

(E)

(G)

biliary anomalies

(C)

(F)

(H)

Figure 1.18 The eight most common variations in the anatomy of the arterial
supply (cystic artery) to the gallbladder.

(A)

The cystic duct arises from the neck of the gallbladder and in
80% of people descends to join the common hepatic duct in its
supraduodenal course. Its length varies widely but its luminal
diameter is usually between 1 and 3 mm. The mucosa of the
cystic duct is arranged in spiral folds (valves of Heister) (33).
In a small number of cases, the cystic duct joins the right
hepatic duct or occasionally a right hepatic sectoral duct.
The gallbladder receives its blood supply by the cystic artery,
the anatomy of which varies widely (Fig. 1.18). The most common variant arises directly from the right hepatic artery, then
dividing into an anterior and posterior branch. The venous
drainage of the gallbladder is directly through the gallbladder
fossa to the portal vein in segment 5 (Fig. 1.19).

The biliary anatomy described above, comprising a right and


left hepatic duct joining to form a common hepatic duct
occurs in between 57% (23) and 72% (8) of cases. This variance may be explained by Couinauds (23) description of a
triple confluence of right posterior sectoral duct, right anterior sectoral duct, and left hepatic duct in 12% of cases, which
Healey and Schroy do not describe.
There are many other abnormalities in biliary anatomy.
Couinaud described a right sectoral duct joining the main bile
duct in 20% of individuals (right anterior sectoral in 16%,
right posterior sectoral in 4%). In addition, a right sectoral
duct (posterior in 5%, anterior in 1%) may join the left hepatic
duct in 6% of cases. In 3% of cases, there is an absence of a
defined hepatic duct confluence with all the sectoral ducts
joining separately and in 2% the right posterior sectoral duct
may join the neck of the gallbladder or be entered by the cystic
duct (23) (Fig. 1.20).
Similarly, there are common variations of the intrahepatic
biliary anatomy. Healey and Schroy (20) describe the classical
intrahepatic biliary arrangement outlined above in 67% of

(B)
Figure 1.19 (A) Venous drainage of the gallbladder. (B) The lymphatic drainage of the gallbladder towards the coeliac axis.

10

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS


cases, with ectopic drainage of segment 5 in 9%, segment 6 in
14%, and segment 8 in 20% of the cases. In addition, they
describe a subvesical duct in 20% to 50% of the cases (8,37).
This subvesical duct may lie deeply embedded in the cystic
plate and can join either the common or right hepatic ducts.
This duct does not drain any specific area of the liver and never
communicates with the gallbladder, but may be damaged during cholecystectomy and therefore contribute to postoperative
biliary leak. On the left side, the commonest anomaly is a common union of ducts of segments 3 and 4 (25% of cases), and in
only 2% does the segment 4 duct independently join the
common hepatic duct (Fig. 1.21).
Gross described a number of anomalies of the accessory
biliary apparatus in 1936 (38). These include bilobed and

ra

ra

rp

Ih

Ih

rp

12%

57%
(A)

(B)
ra

ra

Ih
rp

Ih
rp

20%

4%

16%
C2

C1
(C)
ra

ra
rp

rp

Ih

Ih

1%

5%

6%

D2

D1
(D)

4
4

ra

ra

rp
2

rp

1
3%

2%

1%

E1

E2

(E)

ra
rp
Ih

2%
(F)
Figure 1.20 Main variations of the hepatic duct confluence.

duplicated gallbladder (39,40), septum and diverticulum of


the gallbladder, and variations in cystic duct anatomy including a double cystic duct (41). More rare is agenesis of the gallbladder (42,43) (Fig. 1.22). Furthermore, the gallbladder may
be abnormally positioned, either lying deep within the liver
parenchyma or lying under the left liver (44).
The union of the cystic duct with the common hepatic duct
may be angular, parallel, or spiral. The most frequent union is
angular (75%) (45), while the cystic duct may run parallel with
the hepatic duct in 20%, both encased in connective tissue. In
5% of cases, the cystic duct may approach the hepatic duct in
a spiral fashion, usually passing posteriorly to the common
hepatic duct before entering on its left side (Fig. 1.23).

the arterial blood supply of the bile ducts


The hepatic artery usually arises as one of the three named
branches of the coeliac trunk, along with the left gastric and
splenic arteries (Fig. 1.24). The first named branch of the
hepatic artery is the gastroduodenal artery and either of these
arteries may then give rise to the right gastric and retroduodenal arteries (Fig. 1.24). The hepatic artery then divides into
right (giving rise to the cystic artery) and left hepatic arteries.
This arrangement holds true for 50% of cases.
In nearly 25% of cases, the right hepatic artery arises separately from the superior mesenteric artery, indicative of the
joint fore- and mid-gut origin of the liver (Fig. 1.25). In the
remaining 25% of cases, the left hepatic artery arises from the
left gastric artery. Occasionally, other variations will occur.
These variations will be readily apparent to an experienced
surgeon at operation. The authors do not advocate preoperative angiography to delineate these anomalies prior to routine
hepatectomy.
The extrahepatic biliary system receives a rich arterial blood
supply (46), which is divided into three sections. The hilar section receives arterioles directly from their related hepatic arteries and these form a rich plexus with arterioles from the
supraduodenal section. The blood supply of the supraduodenal
section is predominantly axial. Most vessels to this section arise
from the retroduodenal, right hepatic, cystic, gastroduodenal,
and retroportal artery. Usually, eight small arteries, each 0.3 mm
in diameter, supply the supraduodenal section. The most
important of these vessels run along the lateral borders of the
duct and are referred to as the 3 oclock and 9 oclock arteries.
Of the arteries supplying the supraduodenal section, 60% run
upward from the major inferior vessels while 38% run downward from the right hepatic artery. Only 2% are nonaxial, arising directly from the main trunk of the hepatic artery as it runs
parallel to the bile duct. The retropancreatic section of the bile
duct receives its blood supply from the retroduodenal artery.
The veins draining the bile duct mirror the arteries and also
drain the gallbladder. This venous drainage does not enter the
portal vein directly but seems to have its own portal venous
pathway to the liver parenchyma (47).
It has been proposed that arterial damage during cholecystectomy may result in ischemia leading to postoperative stricture of the bile duct (47), although it seems unlikely that
ischemia is the major mechanism in the causation of bile duct
stricture after cholecystectomy.

11

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


7

6
91%
7

8
7

86%

7
8

6
5%

4%

(A) seg V

5
10%

2%

2%

(B) seg VI

7
6

80%

6
5

20%

a 67%

b 1%

(C) seg VIII


3
c 1%
2

2
3

d 25%

e 1%
2

3
f 1%
2

3
g 4%
(D) seg IV
Figure 1.21 Variations of the intrahepatic biliary anatomy.

the anatomy of biliary exposure


Although intraoperative ultrasound has made easier the location of dilated intrahepatic biliary radicals, surgical exposure
of the extrahepatic biliary confluence and the segment 3 duct
demands knowledge of precise anatomical landmarks. Biliary
enteric anastomosis necessitates precise bile duct exposure to
facilitate the construction of a mucosa to mucosa apposition
(36,4850).
To expose the extrahepatic biliary confluence, the base of the
quadrate lobe (segment 4) is lifted upward and Glissons capsule is incised at its base (see Fig. 1.16) (51). This technique is
also sometimes referred to as lowering the hilar plate. In only
1% of cases is this made difficult by any vascular imposition
between the hilar plate and the inferior aspect of the liver. This
maneuver will expose considerably more of the left hepatic
duct than the right, which runs a shorter extrahepatic course.

12

Contraindications to this approach include patients with a


very deep hilum, which is displaced upward and rotated laterally (36), and those patients who have undergone removal or
atrophy of either the right or left livers resulting in hilar rotation. In this situation, the bile duct may come to lie behind the
portal vein.
When approaching the segment 3 duct (segment 3 hepaticojejunostomy), follow the round ligament (in which runs
the remnant of the obliterated umbilical veins) through the
umbilical fissure to the point where it connects with the left
branch of the portal vein within the recessus of Rex. This
junction may sometimes be deeply embedded within the
parenchyma of the fissure. The bile ducts of the left liver are
located above the left branch of the portal vein, whereas the
corresponding arteries lie below the portal vein. Dissection of
the round ligament on its left side allows exposure of either

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS

(A)

(B)

(D)

liver split to the left of the umbilical fissure in order to widen the
fissure to achieve adequate access to the biliary system.
Access to the right liver system is less readily achieved than
to the left as the anatomy is more imprecise. However, intraoperative ultrasonography greatly enhances the ability of the surgeon to locat e these ducts at surgery. The ideal approach on
the right side is to the segment 5 duct (52), which runs on the
left side of its corresponding portal vein (23). The duct is
exposed by splitting the liver over a short distance to the right
of the gallbladder fossa, commencing at the right side of the
porta hepatis. The segment 5 duct should lie relatively superficially on the left aspect of the portal vein to that segment.

(C)

Figure 1.22 Main variations in gallbladder and cystic duct anatomy:


(A) bilobed gallbladder; (B) septum of gallbladder; (C) diverticulum of gallbladder; (D) variations in cystic duct anatomy.

(A) 75%

(B) 20%

(C) 5%

Figure 1.23 Different types of union of the cystic duct and common hepatic
duct: (A) angular (75%); (B) parallel (20%); (C) spiral (5%).

the pedicle or anterior branch of the duct from segment 3.


This dissection is achieved by mobilizing the round ligament
and pulling it downwards, thereby freeing it from the depths
of the umbilical fissure. This procedure usually requires the
preliminary division of the bridge of liver tissue that runs
between the inferior parts of segments 3 and 4. The umbilical
fissure is then opened and with downward traction of the
ligamentum teres an anterior branch of the segment 3 duct is
exposed on its left side.
Sometimes it may be necessary to perform a superficial liver
split to gain access to this duct. In the usual situation of chronic
biliary obstruction with dilatation of the intrahepatic bile ducts,
the segment 3 duct is generally easily located above the left
branch of the portal vein. However, in the situation of left liver
hypertrophy, it may be necessary to perform a more extensive

radiological anatomy of the liver


Accurate preoperative localization of liver pathology using
radiological techniques is of increasing importance, as any
potential resection depends largely on the segmental localization. Imaging is generally performed using ultrasound,
computed tomography (CT), and magnetic resonance (MR).
Ultrasound is excellent for imaging bile ducts, cysts,
abscesses, and tumors. Hepatic circulation can also be accurately assessed using a Doppler technique. Ultrasound is also
the imaging modality of choice for the biliary tree. However,
the accuracy of ultrasound imaging is very operator dependent, and fine detail can be limited. Examination is limited by
body habitus, and can be restricted by overlying bowel gas.
CT scanning is an excellent method of assessing the liver
parenchyma. It is able to identify a variety of different pathologies, and CT with IV contrast is the most commonly used
method of imaging liver metastases. MR is excellent for the
imaging and characterizing primary liver tumors, and is useful
for the identification of hemangiomas, which can resemble
metastases on CT scanning.
Methods for defining segmental anatomy on ultrasound,
CT, and MR images follow the anatomical landmarks previously described (53). These methods generally involve using
three vertical planes along the lines of the main hepatic veins
to divide the liver into its four sectors, with a transverse scissura along the portal vein further subdividing these four sectors to give the eight Couinaud segments. These anatomical
landmarks are generally easily identifiable on standard imaging. The middle hepatic vein, left hepatic vein, and ligamentum teres provide good landmarks for dividing the left liver
into its four segments. The right hepatic vein can usually be
clearly seen dividing the right liver into its two sectors.

hepatic veins
In an oblique ultrasonic view, the three hepatic veins join the
IVC to form a characteristic W, with its base on the IVC. A
similar view can be seen on CT scan. These veins are usually
easily seen: the left hepatic vein separating segment 2 from segments 3 and 4, the middle hepatic vein separating segment 4
from 5 and 8, and the right hepatic vein separating 5 and 8
from 6 and 7.

portal system
The portal supply to the left lobe, when viewed obliquely, can
be seen as a side-on H, with the left portal vein giving its

13

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

Left branch of the hepatic artery


Right branch of
the hepatic artery
Hepatic artery

3 o'clock artery
9 o'clock artery
Common hepatic artery
Retroduodenal artery

Gastroduodenal artery

(A)

M.H. artery
L.H. artery
R.H. artery

Left gastric

Cystic

Aorta

Proper hepatic

Celiac trunk

Right gastric
Splenic

Supraduodenal

Common hepatic

Gastroduodenal
(B)

Figure 1.24 (A) The biliary duct blood supply; (B) conventional arterial anatomy of the liver (50%).

branch to segment 2, before dividing into the terminal


branches to 3 and 4.
The portal supply to the right lobe also demonstrates a sideon H in the oblique view. The right branch of the portal vein
forms the cross bar of the H, with the branches to segment 5 to
8 forming the arms.

gallbladder, ligamentum venosum,


and falciform ligament
Radiological landmarks of these structures are fallible
(Figs. 1.261.28). Significant variations in intrahepatic vascular anatomy may result in incorrect identification of lesion
location. A study by Rieker et al. looked at CT scans of patients
who underwent liver resection. The location of the lesion was

14

identified using the landmarks outlined above. The scans were


then reviewed, with the lesion being attributed to the nearest
portal branch. Sixteen percent of lesions had a different segmental location if the portal branch was used instead of the
conventional technique (Fig. 1.29) (54).

key points

A full understanding of the lobar, sectoral, and segmental anatomy of the liver and biliary system is
an essential prerequisite for successful liver surgery.
The surgeon must appreciate the wide variation in
extrahepatic biliary anatomy.

SURGICAL ANATOMY OF THE LIVER AND BILE DUCTS

4a

8
(A)

IVC

(B)

(C)

(D)

(E)

(F)

Figure 1.27 CT scan of upper liver in venous phase showing the left, middle
and right hepatic veins draining into the inferior vena cava (IVC).

Figure 1.25 Variations in anatomy of hepatic arterial supply.

Figure 1.28 CT scan of the liver in portal phase showing the left portal vein
passing anteriorly between segments 3 and 4 within the recessus of Rex.

RAPV
LPV

RPPV

Figure 1.26 Portal phase CT scan through porta hepatis showing the left
portal vein (L) lying centrally and the anterior (RA) and posterior (RP)
divisions of the right portal vein (R).

MPV

Figure 1.29 Percutaneous direct portogram showing the relationships of the


anterior (RAPV) and posterior (RPPV) to the main (MPV) and left (LPV)
portal veins.

15

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

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30. Couinaud C. Surgical anatomy of the liver revisited. C Couinaud, 15 rue


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Anatomy of the pancreas


Margo Shoup and Jason W. Smith

topography of the pancreas


The shape and size of the pancreas are highly variable but in
general it has a roughly trapezoidal shape and lies in the retroperitoneum of the upper abdomen (1). It is a finely lobular
structure with a tan to dull yellow color that reaches from the
medial concavity of the duodenum up and to the left terminating at the hilum of the spleen. The volume of the pancreas
increases rapidly during childhood, plateaus from 20 to
60 years, and then steadily decreases; however, the percentage
of parenchyma versus fat in the pancreas continues to increase
during life slowly replacing functional tissue (2) (Fig. 2.1).
The pancreas is divided into three major regions, the head
and uncinate, the neck, and the body and tail (3). The head is
the most medial portion of the gland. It is the widest and
thickest part, having the most globular ultrastructure and is
cradled in the concavity of the duodenum lying just to the
right of the second lumbar vertebra (1). There is an inferior
projection to the head of the pancreas that lies posterior to the
superior mesenteric vessels, which makes up the uncinate process. The head and uncinate are intimately associated with the
duodenum, sharing an abundant network of anastomosing
vessels. The posterior surface of the head of the pancreas is in
apposition to the inferior vena cava, aorta, right spermatic and
ovarian vessels, and right renal vessels and separated from
them by the avascular fusion fascia of Treitz (4). The anterior surface is covered by the transverse colon and its
mesentery (5,6).
The neck of the pancreas is 2 to 3 cm in length and overlies
the confluence of the superior mesenteric vein (SMV) and
splenic vein by which it is grooved. It is related superiorly to
the pylorus and first portion of the duodenum (3,4).
The body of the pancreas extends from body of the second
lumbar vertebra over the left kidney and begins to taper into
the tail as it reaches the hilum of the spleen. The prismatic
shape of the pancreas flattens in the tail. The splenic vein runs
the length of the pancreas on the posterior surface, while the
artery courses along the superior edge of the body. The body
of the pancreas lies over the aorta and the left renal pedicle and
kidney and is separated from these structures by the fusion
fascia of Toldt (4). Inferiorly, it abuts the mesentery of the
transverse mesocolon, while superiorly and anteriorly it abuts
the stomach but is separated from it by the posterior parietal
peritoneum (7).

ductal anatomy of the pancreas


There are numerous configurations of the ducts of the pancreas and their relationships to each other, the duodenum and
the common bile duct. The significance of the pancreas
became understood only after the discovery of the main pancreatic duct by Wirsung in 1643. He noted that there was a
duct that traversed the length of the organ with numerous

tributary ducts coming off at near right angles and that this
duct opened into the duodenum, and he saw that there were
occasionally two ducts in the gland (1). It was Santorini who
finally concluded that, in the normal condition, there existed
two ducts with the smaller of the two emptying into the duodenum by way of a small papilla approximately 2 cm nearer to
the stomach than the major duct and this smaller duct bears
his name (5). The smaller duct is patent all the way to the duodenum in only 60% of specimens and the duct of Wirsung
represents the larger of the two; however, in about 10% of
specimens, the duct of Santorini is the main drainage for the
pancreas. Also in about 10% of cases, the two ducts are not in
communication with each other (1) (Fig. 2.2). The parenchyma of the pancreas consists of small lobules divided by
connective tissue. These lobules are centered around the main
tributary ducts that run to the main pancreatic duct. Smaller
branches off of these tributaries define further septated regions
within the lobules of pancreatic tissue. The main branches of
the pancreatic duct tend to meet the main duct on its superior
and inferior aspect. The diameter of the main pancreatic duct
is reported to be between 2.6 and 4.8 mm in the head, 2.0 and
4.0 mm in the body, and 0.9 and 2.4 mm in the tail (3). The
duct runs in a relatively superficial position in the tail and after
traversing the neck of the pancreas it dives deep into the parenchyma as it crosses the head and is near the dorsal surface of
the pancreas as it nears the confluence with the common bile
duct (CBD) and the duodenum (1).
The lower portion of the CBD lies in contact with the head
of the pancreas for between 2 and 7 cm and 40% of the time it
lies in a groove between the surface of the pancreas and the
duodenum. In the remainder of cases, it lies within the parenchyma of the pancreas (7). During embryological development, the lower duct of Wirsung arises in the ventral pancreatic
bud adjacent to the early hepatic duct. Therefore, the association of the duct of Wirsung with the CBD is a consistent feature of the ductal anatomy of the pancreas (1). The duct of
Wirsung and the CBD unite 6 to 8 mm within the papilla and
form a common channel, which is slightly dilated and referred
to as the ampulla of Vater. In just over 10% of cases, the two
ducts do not form a short common channel and instead enter
the duodenum independently on the papilla (5).

arterial anatomy of the pancreas


The pancreas enjoys an abundant arterial blood supply that
draws from both the celiac axis and the superior mesenteric
artery (SMA). The pancreas is supplied from the celiac axis by
the superior pancreaticoduodenal artery from the gastroduodenal artery (GDA), and the dorsal pancreatic and pancreatica
magna arteries from the splenic artery (Fig. 2.3). The distal
and inferior borders of the pancreas are supplied by the caudal
and inferior pancreatic arteries, which are formed by

17

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

Figure 2.1 Overview of the relationship of the pancreas to other important structures in the upper abdomen. Plate 1098, From Anatomy of the Human Body,
Henry Gray 1918.

(A)

(B)

(C)

Figure 2.2 (A) Duct of Santorini is patent all the way to the duodenum. (B) Duct of Santorini is the main drainage. (C) The two ducts are not in communication
with each other.

ramifications with the dorsal pancreatic, pancreatica magna,


and splenic arteries. The SMA gives rise to the more variable
inferior pancreaticoduodenal (IPD) artery, which divides into
branches to form both an anterior and posterior anastomotic
arcade with branches from the superior pancreaticoduodenal
artery (8).
Superior Pancreaticoduodenal Artery
The superior pancreaticoduodenal is a short branch of the
GDA that arises after the takeoff of the right gastroepiploic
artery (Fig. 2.4). It is angiographically identifiable in about
10% of specimens and is generally about 8 mm in length (9).
Although rare, it is reported to occasionally arise from the left
hepatic artery. When present, the superior pancreaticoduodenal artery divides into anterior and posterior branches, which
anastomose with the inferior branches from the SMA. In the
remaining cases, the posterior superior pancreaticoduodenal

18

(PSPD) artery is seen arising from the GDA prior to the right
gastroepiploic takeoff. The anterior superior pancreaticoduodenal (ASPD) artery has a caliber between 1 and 3 mm and is
considered the most important blood supply to the head of the
pancreas. In the majority of cases, it is a terminal branch of the
GDA after it has given off the PSPD and the right gastroepiploic arteries. The ASPD can be duplicated in up to 7% of
cases and rarely is absent. Case reports of extremely rare
anomalies exist, reporting the origin of this artery from almost
all of the major branches of the celiac and SMAs (9).
Posterior Superior Pancreaticoduodenal Artery
This artery forms the superior portion of the posterior arcade
that forms anastomoses with the posterior branch of the IPD
artery. The PSPD artery is most commonly found as a branch
of the GDA 1 to 2 cm after the takeoff of the hepatic artery (10).
Up to 10% of cases may see the PSPD arise from the superior

ANATOMY OF THE PANCREAS

Cystic artery

Probe passed through epiploie foramen

a
S

C r e
a t o
r

O x e n t e

Figure 2.3 Arterial anatomy of the pancreas, the celiac axis and its major branches. Plate 532, From Anatomy of the Human Body, Henry Gray 1918.

pancreaticoduodenal and in rare instances may arise from any


of the hepatic arteries. The most common course of the PSPD
after it leaves the GDA posteriorly is it runs over the portal vein
(PV) and the anterior edge of the top of the pancreas where it
enters the gland and finds the common bile duct and makes a
right-handed spiral around the duct passing posterior to it just
above the ampulla. It then runs deep in the parenchyma of the
pancreas to find its connection with the posterior inferior
artery. The PSPD gives off collateral branches to form the blood
supply to the intrapancreatic portion of the common bile duct,
it generally gives off the supraduodenal artery and occasionally
the retroduodenal artery, rarely it may give a branch to the gallbladder or an accessory right hepatic artery (10).
Inferior Pancreaticoduodenal Artery
The IPD artery is present in about 70% of cases and is the
common trunk that gives rise to the anterior and posterior
inferior pancreaticoduodenal (AIPD and PIPD) arteries that
form the anastomotic arcades supplying the head of the pancreas (11). In the remaining 30% of cases, the AIPD and PIPD
arise directly from the SMA. The IPD may arise directly from
the SMA as the first collateral branch from 2 to 5 cm distal to
the origin and take a short course from its posterior takeoff
into the inferior edge of the pancreatic parenchyma, or alternatively, it may arise as a common trunk with the first jejunal

branch, the pancreaticoduodenaljejunal (PDJ) trunk in which


case it takes a longer course to the pancreas. The IPD crosses
posterior to the SMV and the posterior surface of the pancreas
and does not give off any branches prior to dividing into its
anterior and posterior termini (11).
Anterior and Posterior Inferior Pancreaticoduodenal Arteries
These arteries supply the inferior part of the anastomotic
arches that supply the head of the pancreas. They arise most
often from a common IPD artery. They may also originate
directly from the SMA or less commonly directly from the first
jejunal artery or from a replaced hepatic artery. The main
course of the AIPD is to follow the inferior curve of the pancreas and find its partner the ASPD (12). It may give off a
branch to the duodenaljejunal flexure or to form a transverse
pancreatic artery. The PIPD runs more posterior and cephalad
than the AIPD and ultimately finds the PSPD or alternatively
terminates as small end arteries. It may supply a collateral
branch to the transverse pancreatic artery when present (12).
Dorsal Pancreatic Artery
The main blood supply to the neck and body of the pancreas is
the dorsal pancreatic (DP) artery. It most commonly arises
from the splenic artery near its origin at the celiac axis (13). It
may also take its origin from the celiac trunk itself, the

19

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

S t o m a c h

Figure 2.4 Arterial anatomy of the pancreas, demonstrating the gastroduodenal and its branches of the anterior and posterior pancreaticoduodenal arteries forming the anastomotic arcades with the branches from the superior mesenteric artery. Plate 533, From Anatomy of the Human Body, Henry Gray 1918.

common hepatic or the GDA. Alternatively, the DP may arise


from the SMA. The course of the DP artery is usually in the
form of an inverted T with a right and left branch that form
after a short 1 to 3 cm course. When the artery arises from the
splenic artery, it tends to angle back to the right, if it takes off
from the celiac, hepatic, or GDA, then it transverses the neck in
a leftward direction. When coming from the SMA it comes up
from the bottom of the pancreas. The right branch of the DP
forms an anastomosis with left anastomotic pancreatic artery
from the ASPD. The left branch becomes the transverse pancreatic artery (13).
Caudal and Great Pancreatic Arteries
The great pancreatic artery is often present and is given off
from the splenic artery at the junction of the body and tail. It
collateralizes with the transverse pancreatic artery. The caudal
pancreatic artery takes its origin from the left gastroepiploic,
the distal splenic artery or a branch from the splenic hilum
and forms anastomotic connections with the great pancreatic
and transverse pancreatic arteries (3).
The arterial blood supply to the pancreas is rich and
complex. Most of the primary arterial conduits form some

20

anastomotic connection and this shared blood supply is one of


the challenges of pancreatic surgery. When operating in the
deepest recesses of the abdomen, having an intimate knowledge of the standard arterial anatomy as well as the most common alternatives will allow the pancreatic surgeon to maximize
patient safety. That same surgeon must keep in mind that the
arterial anatomy in this area is subject to wide variation and
that one must always be prepared to address the aberrant anatomy. To that end, having good preoperative imaging to establish before the operation what the arterial anatomy is can be a
valuable aid whether by angiography or by computed tomography (CT) angiography.
Venous Drainage of the Pancreas
The veins of the pancreas follow the course of the corresponding arteries in most cases. They are generally more superficially located than the arteries and depending on the location
in the pancreas drain into the PV, SMV, the inferior mesenteric
vein, or the splenic vein. In the head of the pancreas, there is a
venous arcade that mirrors the arterial anastomoses and of the
four main veins all, but the PSPD vein, which empties directly
into the PV, find their way to the SMV. In addition, there are

ANATOMY OF THE PANCREAS

12

12p1

12b1

12a1

10
9

12p2

11

12a2
3
8a

16
8p

10

14a

2
6
4

14b

13a
17a

14c

18

14d

17b
14V

13b

15

14d

Figure 2.5 Lymphatic drainage of the pancreas.

numerous small bridging veins between the head of the pancreas and the SMV and PV as they course behind the pancreas,
which must be carefully ligated during a resection. The fact
that there are rarely venous branches that enter the SMV or PV
on their anterior surfaces makes the dissection along the plane
anterior to these vessels possible during pancreaticduodenectomy. Two large veins drain the body and tail of the pancreas,
the splenic vein, which courses along the superior edge of the
pancreas and the transverse pancreatic vein along the
inferior margin.
The portal vein is formed on the posterior surface of the
neck of the pancreas by the confluence of the splenic vein and
the SMV. The inferior mesenteric vein may join at this point as
well, but more commonly joins the splenic vein or SMV proximal to the confluence (Fig. 2.4).

lympatic drainage of the pancreas


The lymphatic drainage of the pancreas is rich and drains each
lobular division with frequent anastomotic connections and
the ultrastructure is similar to that in other solid organs of the
abdomen(14) (Fig. 2.5). These lobular lymphatics coalesce to
form several trunks that empty into the primary lymph node
basins for the pancreas before quickly reaching the thoracic
duct (15). The drainage of the pancreas can be roughly divided
into right and left side based on the ventral and dorsal anlage
of the primordial pancreas. The left side of the system drains
the upper portion of the head, the neck, and body and tail,

while the right side drains the lower portion of the head, which
developed from the ventral bud and constitutes the retroportal
lymphatics (15,16). The superior pancreatic nodes drain the
upper half of the neck, body and tail of the pancreas, and a
portion of the head. They primarily lie along the superior border of the gland or in the gastropancreatic fold and gastrohepatic ligament (17). The inferior pancreatic nodes similarly
drain the inferior half of the gland and lie along the inferior
border as well as draining into the superior mesenteric nodes
or the periaortic nodes. The anterior nodes are located along
the surface of the pancreas that lies adjacent to the duodenum
and are called the infrapyloric lymph nodes and the pancreaticoduodenal nodes. These anterior nodes may also drain into
nodes along the root of the transverse colonic mesentery that
is adjacent to the head of the pancreas. The posterior nodes
run along the posterior pancreaticoduodenal border and
include the nodes along the lower portion of the common bile
duct, portal vein and nodes at the origin of the SMA. The tail
of the pancreas forms several lymphatic trunks that reach out
into the hilum of the spleen and form the superior and inferior
lymph nodes (3,16). This simplified lymphatic mapping system is that adapted by the International Union against Cancer
(UICC). A more comprehensive and clinically useful system
was developed by the Japanese Research System, which divides
lymph node stations into 18 different designations and rates
them according to the likelihood of metastatic spread. Nodal
stations 13 and 17 are the most likely to harbor disease with

21

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Right gastroepiploic vein
Splenic vein

Portal vein

PSPD-V
Gastrocolic trunk

Superior mesenteric vein


AIPD-V
PIPD-V

First jejunal
tributary

ASPD-V
Figure 2.6 Major venous drainage for the pancreas.

47% and 29%, respectively (18,19) (Fig. 2.6). Classification of


lymphatic involvement will become increasingly important as
increasing numbers of targeted therapies become available in
pancreatic cancer.

innervation of the pancreas


The pancreas receives fibers from both the sympathetic and
parasympathetic nervous systems. The sympathetic innervation is via the splanchnic nerves, which carry both afferent
fibers and efferent fibers, while the parasympathetic innervation is via the vagus nerve, which also has afferent and efferent
supply to the pancreas. Parasympathetic innervation provides
stimulatory signals to the islet cells to increase insulin secretion in response to food intake, while increased sympathetic
tone suppresses insulin secretion and stimulates the secretion
of glucagon (20,21). Efferent pain fibers are found in both the
splanchnic and vagal nerves and localization of these fibers has
been a difficult clinical problem in the management of pain in
both inflammatory and malignant diseases of the pancreas.
The right, and more prominently the left, celiac ganglion provide the majority of the direct innervation to the posterior
head, body, and tail of the pancreas via fibers that course along
the splenic artery (16). Neural ganglia around the common
hepatic artery also provide fibers that course along the GDA to
the head and uncinate process of the pancreas (22). Recently, it
has been shown that the celiac ganglion bearing the splanchnic
efferent fibers can be identified by endoscopic ultrasound and
precise localization of neurolytic therapies can be applied to
improve the success of these approaches (23,24).
Enteropancreatic nervous connections have also been demonstrated from both the stomach and proximal duodenum to
the pancreas (2426). These connections suggest that there is
crosstalk directly from the gastrointestinal tract to the pancreas
coordinating exocrine and/or endocrine secretions with
gut function.

22

The pancreas lies in the recesses of the upper abdomen and


remains one of the most challenging organs to manage from
a clinical or operative standpoint. Its rich blood supply, close
associations with major vascular structures, intimate relation
to the common bile duct, and the attachments to the duodenum and spleen all contribute to the complexity of surgical
intervention in both malignant and benign disease (7). A
thorough understanding of the three dimensional relationship of the arterial blood supply and major veins in proximity to the pancreas make approaching pancreatic resection
possible. As we move into an era of minimally invasive surgery, being able to recognize the anatomy and its variations
with minimal cues from adjacent structures will become
increasingly important and continued study of these complex relationships allows the mind to know, so that the eye
may see.

references
1. Opie EL. Anatomy of the Pancreas and its Variations. Disease of the Pancreas: Its Cause and Nature, 1st edn. Philadelphia, PA: J.B. Lippincott
Company, 1903: 359.
2. Saisho Y, Butler AE, Meier JJ, et al. Pancreas volumes in humans from
birth to age one hundred taking into account sex, obesity, and presence of
type-2 diabetes. Clin Anat 2007; 20: 93342.
3. Skandalakis LJ, Colborn GL, Skandalakis JE. Surgical anatomy of the pancreas. In: Baker RJ, Fischer JE, eds. Mastery of Surgery, Vol. 2, 4th edn.
Philadelphia, PA: Lippincott Williams & Wilkins, 2001: 2448.
4. Kuroda A, Nagai H. Surgical anatomy of the pancreas. In: Howard J,
Idezuki Y, Ihse I, Prinz R, eds. Surgical Diseases of the Pancreas, 3rd edn.
Baltimore, MD: Lippincott Williams & Wilkins, 1998: 869.
5. Cattell RB, Warren KW. The anatomy and physiology of the pancreas. In:
Cattell RB, Warren KW, eds. Surgery of the Pancreas. Philadelphia, PA:
Saunders, 1953.
6. Hollinshead WH. The thorax, abdomen and pelvis. In: Hollinshead WH,
ed. Anatomy for Surgeons. Vol. 2. New York: Medical Department, Harper
and Row Publishers, 1971: 430.
7. Anson BJ, McVay CB, Callander CL. The Abdomen. Surgical Anatomy.
Philadelphia, PA: Saunders, 1971.
8. Woodburne RT, Olsen LL. The arteries of the pancreas. Anat Rec 1951;
111: 25570.
9. Bertelli E, Di Gregorio F, Bertelli L, Mosca S. The arterial blood supply of
the pancreas: A review. I. The superior pancreaticoduodenal and the anterior superior pancreaticoduodenal arteries. An anatomical and radiological study. Surg Radiol Anat 1995; 17: 97106, 1013.
10. Bertelli E, Di Gregorio F, Bertelli L, Civeli L, Mosca S. The arterial blood supply of the pancreas: A review. II. The posterior superior pancreaticoduodenal
artery. An anatomical and radiological study. Surg Radiol Anat 1996; 18: 19.
11. Bertelli E, Di Gregorio F, Bertelli L, Civeli L, Mosca S. The arterial blood
supply of the pancreas: A review. III. The inferior pancreaticoduodenal
artery. An anatomical review and a radiological study. Surg Radiol Anat
1996; 18: 6774.
12. Bertelli E, Di Gregorio F, Bertelli L, Orazioli D, Bastianini A. The arterial
blood supply of the pancreas: A review. IV. The anterior inferior and posterior pancreaticoduodenal aa., and minor sources of blood supply for the
head of the pancreas. An anatomical review and radiologic study. Surg
Radiol Anat 1997; 19: 20312.
13. Bertelli E, Di Gregorio F, Mosca S, Bastianini A. The arterial blood supply
of the pancreas: A review. V. The dorsal pancreatic artery. An anatomic
review and a radiologic study. Surg Radiol Anat 1998; 20: 44552.
14. Navas V, OMorchoe PJ, OMorchoe CC. Lymphatic system of the rat pancreas. Lymphology 1995; 28: 420.
15. Pissas A. Anatomoclinical and anatomosurgical essay on the lymphatic
circulation of the pancreas. Anat Clin 1984; 6: 25580.
16. Donatini B, Hidden G. Routes of lymphatic drainage from the pancreas:
A suggested segmentation. Surg Radiol Anat. 1992; 14: 3542.

ANATOMY OF THE PANCREAS


17. Hartley M, Finch-Jones M. Anatomy of the pancreas. In: Poston G,
Blumgart L, eds. Surgical Management of Hepatobiliary and Pancreatic
Disorders, 1st edn. London: Martin Dunitz, 2002: 1928.
18. Bogoevski D, Yekebas EF, Schurr P, et al. Mode of spread in the early phase
of lymphatic metastasis in pancreatic ductal adenocarcinoma: Prognostic
significance of nodal microinvolvement. Ann Surg 2004; 240: 9931000,
discussion 10001.
19. Sakai M, Nakao A, Kaneko T, et al. Para-aortic lymph node metastasis in
carcinoma of the head of the pancreas. Surgery 2005; 137: 60611.
20. Benthem L, Mundinger TO, Taborsky GJ, Jr. Parasympathetic inhibition
of sympathetic neural activity to the pancreas. Am J Physiol Endocrinol
Metab 2001; 280: E37881.
21. Jarhult J, Falck B, Ingemansson S, Nobin A. The functional importance of
sympathetic nerves to the liver and endocrine pancreas. Ann Surg 1979;
189: 96100.

22. Yoshioka H, Wakabayashi T. Therapeutic neurotomy on head of pancreas


for relief of pain due to chronic pancreatitis; a new technical procedure
and its results. AMA Arch Surg 1958; 76: 54654.
23. Levy MJ, Topazian MD, Wiersema MJ, et al. Initial evaluation of the efficacy and safety of endoscopic ultrasound-guided direct Ganglia neurolysis and block. Am J Gastroenterol 2008; 103: 98103.
24. Kirchgessner AL, Liu MT, Gershon MD. In situ identification and visualization of neurons that mediate enteric and enteropancreatic reflexes. J
Comp Neurol 1996; 371: 27086.
25. Holst JJ, Schwartz TW, Knuhtsen S, Jensen SL, Nielsen OV. Autonomic
nervous control of the endocrine secretion from the isolated, perfused pig
pancreas. J Auton Nerv Syst 1986; 17: 7184.
26. Kirchgessner AL, Gershon MD. Innervation and regulation of
the pancreas by neurons in the gut. Z Gastroenterol Verh 1991; 26:
23033.

23

Hepatic resection
Ajay V. Maker and Michael DAngelica

introduction
Though liver anatomy and physiology have been studied for
centuries, liver surgery still is a relatively young field. Just
30 years ago, the mortality of major hepatic resection neared
25%. This high mortality limited its utility and deterred
patients and referring physicians from considering surgery.
The current generation of hepatobiliary surgeons has an
increased understanding of the segmental anatomy of the
organ and has seen a dramatic decrease in the mortality of
liver surgery to nearly 1% largely due to a dramatic decrease in
blood loss (1). This chapter will address the basic principles
and techniques to safely approach liver resection.

basic principles
Surgical Indications: Benign vs. Malignant Disease
Though this chapter focuses on the technical aspects of
hepatic resection, an understanding of when liver resection
is indicated is of paramount importance. Due to advances
in modern imaging techniques and an increased knowledge of the natural history of liver lesions, tumors that may
have been resected in the past for diagnostic uncertainty
are now often observed. Similarly, malignant lesions that
were not resected in the past but referred for nonsurgical
therapy are now being treated with resection. Indications
for specific benign and malignant processes are outlined
in other chapters; however, the general principles are
mentioned here.
Benign Disease
Partial hepatectomy for benign conditions should be parenchymal preserving and reserved for lesions that are symptomatic, have premalignant potential, or carry an unclear diagnosis.
Wide margins are not necessary, therefore in some cases, for
example, focal nodular hyperplasia (FNH) or hemangiomas,
enucleation may be safely performed, although in some instances an anatomic segmental resection may be the safest
approach (24). This is addressed at the end of the chapter and
detailed in other chapters.
Malignant Disease
Partial hepatectomy for malignant conditions must obtain a
clear surgical margin, and is suitable for well-selected patients
with both primary and metastatic cancer. We have found
increased patient survival with margins of at least 1 cm in
patients undergoing resection for metastatic colorectal cancer
(513), though other series suggest that a negative margin,
regardless of the distance, is sufficient (14,15). The exception
may be in slow-growing tumors with multiple liver metastases, such as neuroendocrine tumors, where tumor debulking
may be of value. As long as the functional remnant liver is
adequate, usually about 25% liver volume in otherwise

24

healthy individuals, excision of tumor can prolong life and in


some cases provide long-term disease-free survival.
Patient Selection
Proper patient selection is critical to both the safety and efficacy of hepatic resection. One should evaluate the patients
general state of health, the condition of the liver, and the
volume of the future liver remnant to properly assess the risk
of general anesthesia, major abdominal surgery, and liver
resection. Subcostal and upper abdominal incisions are painful and may result in respiratory splinting and increased pulmonary complications compared to other incisions (16). For
this reason, assessment of the patients ability to mobilize early
and ambulate postoperatively must not be underestimated.
Though there are many algorithms to evaluate liver function
in patients with chronic liver disease, the Child-Pugh classification is a useful preoperative indicator, and patients with a
Pugh score of B or C should generally not undergo liver resection. Hepatic resection in cirrhotic patients is particularly difficult with operative mortality increasing with advanced Child
classification. Hepatic resection in the setting of portal hypertension is generally not recommended (17), as this condition
predisposes the liver to higher portal pressures and diminished
ability to increase portal flow to the liver remnant postoperatively, thereby inhibiting normal liver regeneration and
increasing the risk of life-threatening bleeding. The cirrhotic
liver has decreased regenerative capacity and impairment in
liver function is greater, lasts longer, and can result in permanent liver failure. A low platelet count, splenomegaly, ascites,
or evidence of varices on preoperative radiography may be the
only findings to alert the surgeon to hepatic dysfunction.
Many noncirrhotic patients that present for hepatic resection have abnormal liver function due to chemotherapy, diabetes, or obesity. These diseased livers carry an increased risk
of functional impairment with large resections and may also
have impaired function despite retained volume (18,19). In
these livers, careful preoperative planning must be done to
achieve a parenchymal sparing resection. Biopsy, if performed, can give clues to the fat content of the liver, as can
preoperative imaging (20). Early data suggest that MRI spectroscopy can also accurately quantify hepatic fat content, and
this may prove to be a useful tool in preoperative liver assessment and operative planning (20,21). In cases where liver
function may be impaired, or where extended resection is
necessary to gain tumor-free margins, portal vein embolization is being employed to induce hypertrophy of the proposed
liver remnant (22,23). No absolute guidelines for embolization can be made; however, preoperatively induced liver
hypertrophy is a valuable tool in planning and executing
major liver resections (24). Furthermore, chronic biliary
obstruction inhibits liver function and, thus patients with

HEPATIC RESECTION
hilar cholangiocarcinomas are also at increased risk of liver
failure postoperatively.
The functional residual liver volume should be calculated to
insure adequate liver function postresection. A healthy, noncirrhotic individual requires a functional hepatic reserve of at
least 20% of the original nontumoral liver volume. The regenerative capacity of the liver should enable full functional compensation within weeks of resection; once greater than 70% of
liver volume is resected, however, there is a risk of clinically
significant liver insufficiency. This risk is minimal if specimen
volume has been replaced with tumor, in which case compensatory hypertrophy will have already occurred.
Preoperative Imaging (See Also Chapters 3, 4, and 11)
Fine-cut triphasic helical computed tomography (CT) with
CT angiogram is the single most useful study in preoperative
evaluation of liver tumors. When the study includes the chest,
abdomen, and pelvis, preoperative staging is reliable and can
identify areas outside of the liver that may need further evaluation or confirm nonoperative candidates. CT can define the
vascular anatomy, identify anatomical variants, determine
resectability, estimate the functional liver residual volume, and
identify preoperative biliary drainage strategies, thereby obviating the need for further radiographic studies. CT angiography in particular has almost prevented the need for traditional
angiography. 3-D reconstruction of the vasculature is particularly helpful in identifying vascular anomalies quickly and
temporally. Furthermore, 3-D reconstruction of the vascular
anatomy may lead to more accurate visualization of tumor
vessel relationships and may be a more accurate study to predetermine the operative line of transection (25). Magnetic
resonance imaging can also provide high-quality vascular and
volumetric assessments of the liver but its principal role is in
characterizing liver tumors of unclear etiology.
In experienced hands, ultrasound is a fast, inexpensive, and
noninvasive modality that can quickly obtain information
regarding tumor size and the amount of liver involvement,
particularly in gallbladder and biliary tumors. It is especially
helpful in distinguishing cysts from solid tumors and should
be used in addition to CT to evaluate cysts for the presence of
septations or mural thickening, which would suggest cystadenoma or a cystadenocarcinoma. Duplex ultrasound is also
particularly helpful as a dynamic study to identify vasculature
in relation to tumor masses.
Anesthetic Techniques
Operative and perioperative morbidity and mortality have
been decreased in part due to changes in anesthetic practices
over the evolution of hepatic resection. A focus on maintaining low central venous pressure (CVP) can greatly reduce
blood loss and keep the operative field clean for proper visualization of the biliary and vascular anatomy during parenchymal transaction. This is accomplished by positioning the
patient in mild Trendelenberg and minimizing intravenous
fluid to maintain systolic blood pressures above 90 mmHg and
urine output to about 25 mL/h. If the IVC is still distended
after mobilization of the liver, parenchymal transection can
wait until central venous pressure is decreased through use of

narcotics, vasodilatory inhalation agents, or direct vasodilators. A central venous pressure of less than 5 mmHg can be
maintained during the periods of liver mobilization and
parenchymal transection. Though a cental venous catheter is a
useful tool to follow the CVP, the surgeon can also look for a
nondistended IVC and for blood coursing through flat intrahepatic veins. If transection is performed under Pringle control, bleeding is generally from hepatic veins, therefore, with a
low hepatic venous pressure, even large tears in hepatic veins
can be visualized to allow ligation or repair without massive
hemorrhage. By Poiseuilles law, blood flow is exponentially
proportional to the radius of the vessel; therefore, even minor
decreases in venous distention can decrease blood loss exponentially. With these techniques, the risk of postoperative renal
failure has not been shown to be significant, nor has the risk of
air embolism, which can be minimized, regardless, by keeping
the patient in about 15 of Trendelenberg (26,27). Normal
resuscitation is performed after the resection is completed and
hemostasis has been achieved.

basic techniques
Positioning, Skin Incision, and Exposure
The patient should be positioned supine with the arms
extended at right angles to the body. Any self-retaining retractor can be utilized, however, we prefer the Goligher retractor to
elevate the costal margin, and this crossbar can be fitted to the
table to form a 45 angle from top of the crossbar to the
xyphoid. The patient should be prepped from the mid-chest to
below the umbilicus, and draped to expose the right chest in
the event a right thoracotomy is necessary to gain additional
exposure. Though some groups routinely make a J-shaped thoracoabdominal incision, in our experience a thoracoabdominal
incision was rarely necessary in over 1800 cases (2). We employ
selective use of diagnostic laparoscopy based on the risk of
unresectable disease (28), and conform the type of incision to
the expected resection. For access to both lobes of the liver, a
bilateral subcostal incision can be used with or without vertical
midline extension. For the great majority of liver resections, we
employ a hockey stick incision, which includes a right subcostal incision with vertical midline extension to the xyphoid.
These incisions, when combined with the Goligher retractor,
provide good exposure of the suprahepatic IVC, even with large
right-sided tumors. We have found a higher rate of incisional
hernia with a Mercedes incision compared to a hockey stick
incision (29). For left-sided resections, a midline incision may
suffice. Occasionally, when there is severe right-sided hepatic
atrophy or exposure to the suprahepatic IVC is necessary for
safety, extension into the right chest can be helpful (Fig. 3.1).
Mobilization
The ligamentum teres is divided between clamps and ligated,
leaving a long secure ligature that is used as a handle to further
expose the porta hepatis. The thin veil of the falciform ligament is incised along its length to free it from the anterior
abdominal wall and expose the ligamentum teres. In obese
individuals, the area where the falciform is fused to the anterior abdominal wall may be invested within a large fat pad.
This fat pad can be removed with diathermy from beneath

25

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


both sides of the exposed fascia, improving exposure and
aiding with fascial reapproximation at the end of the case.
The falciform ligament is divided up to the suprahepatic
IVC (Fig. 3.2).
Bimanual palpation of the liver should be performed to
assess the extent of hepatic disease. Segment 4 should be
carefully retracted cephalad to expose the clear veil of lesser
omentum anterior to the caudate lobe and attaching to the
ligamentum venosum. This is incised, allowing palpation of

Figure 3.1 Incisions for liver resection. B-D, initial upper midline exploration.
A-B-C, ideal for exposure of the whole liver (hockey stick). C-D-E, the classic
chevron incision with A-D (Mercedes) extension. C-D, right subcostal incision. F, thoracoabdominal extension. Source: Blumgart; Surgery of the Liver,
Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

the caudate and celiac axis, and providing access through the
foramen of Winslow to the porta hepatis. Intraoperative ultrasound is used at this point to define the extent of disease, vascular relationships, and to confirm resectability.
To mobilize the right liver, the leaf of the right coronary ligament is dissected from the falciform ligament and carefully
incised over the IVC and territory of the right hepatic vein.
This should be done sharply with downward traction on the
liver and superior traction on the diaphragm. Once the right
hepatic vein is identified, the right coronary ligament is taken
close to the liver surface to its furthest extent laterally and the
right triangular ligament is divided. To complete the mobilization, the right liver must be freed inferiorly. Omental and peritoneal attachments to the liver and gallbladder are divided to
expose the inferior extent of the right triangular ligament. The
retroperitoneal attachments are incised off the right adrenal
gland and the liver can then be rotated medially to expose the
retrohepatic IVC.
If the right liver is to be resected or control of the right
hepatic vein is needed, the multiple small venous branches
from the IVC to the posterior liver must be individually dissected, controlled, and divided. Large accessory inferior right
hepatic veins are common and may require division with a
vascular stapler or control with vascular clamps and ligatures.
It is critical for the surgeon on the left side of the table to
retract the right liver medially to expose these branches and
prevent injury to the cava. When all of these branches are
ligated and divided, all that is left to expose the right hepatic
vein will be a fibrous band of tissue that runs lateral to the
vein, encircles the IVC, and courses posteriorly to the left and
posterior border of the caudate, known as the caval ligament
(Fig. 3.3). A tunnel can be safely created medial to this ligament and lateral to the right hepatic vein with a Kelly clamp or
renal pedicle clamp in order to allow either a ligature or a

Figure 3.2 Mobilization of the liver begins with downward traction on the liver and division of the falciform ligament to the inferior vena cava. Source: Blumgart;
Surgery of the Liver, Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

26

HEPATIC RESECTION
vascular load endo-GIA staple fire. Once this is divided, the
right liver is mobile and the lateral aspect of the right hepatic
vein is exposed.
The left liver is mobilized similarly, however since it does not
lie on the vena cava, an extensive caval dissection is not necessary. Sharp and blunt dissection over the suprahepatic IVC will
expose the groove between the right vein and the common
trunk of the middle and left and middle hepatic veins. Downward traction on the liver and cephalad traction on the diaphragm help expose the left coronary ligament. The groove
between the left and middle hepatic veins can be exposed with
sharp dissection if there is no long intrahepatic common
channel (Fig. 3.4). Care must be taken here to identify the
phrenic vein as it courses on the underside of the diaphragm
to enter the IVC, as it can be inadvertently injured if the triangular ligament is not properly exposed or not divided close to
the liver surface (Fig. 3.5). As the left lateral segment is released

from its peritoneal attachments, it is also useful to place a hand


or laparotomy pad under the left lateral segment and anterior
to the caudate to provide traction and to protect the stomach,
bowel, and spleen from diathermic injury. Further mobilization of the left liver can be accomplished by dividing the lesser
omentum as well as the ligamentum venosum either at the left
portal vein or left hepatic vein insertions to expose these vessels and the underlying caudate lobe.

vascular isolation
Once the liver is mobilized, there are essentially three steps to
safely perform a hepatectomy. These involve vascular inflow
control, vascular outflow control, and parenchymal transection.
Inflow Control
All major hepatic resections require control of the vascular
inflow to be accomplished safely. Furthermore, adequate

Figure 3.3 Multiple small venous branches from the IVC to the posterior liver must be individually dissected and divided. When all of these branches are controlled,
all that is left to expose the right hepatic vein will be a fibrous band of tissue, the caval ligament. A tunnel can be safely created behind this ligament and above the
right hepatic vein with a Kelly clamp. Once this is divided, the entire right liver is mobile and the venous outflow can be encircled and controlled. Source: Blumgart;
Surgery of the Liver, Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

27

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


hepatic arterial and portal venous inflow must be maintained
to the remnant liver. Selective inflow control may be achieved
extrahepatically (30), intrahepatically during parenchymal
transection (1,31), or by intrahepatic pedicle control via hepatotomies (32,33).
In the extrahepatic approach, the hepatic artery and portal
vein branches are dissected at the porta hepatis and controlled
outside of the liver. In this approach, the individual artery and
portal vein have to be separately identified and ligated since
they have not yet entered the liver as a portal pedicle. The
advantages of this approach are early vascular control prior to
transection and demarcation of the liver on its surface. The
disadvantages are a somewhat tedious dissection and the
potential for injury to contralateral structures. The presence of
tumor abutting the hilum may mandate extrahepatic inflow
control. The right hepatic artery usually courses posterior to
the common hepatic bile duct and can be dissected from the
right side of the porta hepatis and controlled. Once divided,
the proximal artery stump can be retracted anteriorly exposing the underlying portal vein. All branches must be carefully
dissected and identified prior to division to insure that there is
no compromise of flow to the future liver remnant, a potentially fatal complication. There is typically a small branch to
the caudate process coming off the right portal vein proximally that may have to be controlled. As opposed to the short
extrahepatic course from the hilum to the right liver, the vascular inflow to the left liver can be controlled in the umbilical
fissure (34). The left portal vein and duct are mobilized by
lowering the hilar plate. Here the left hepatic artery is typically
found running cephalad along the left side of the porta hepatis
anteriorly. It is prudent to insure that one has not inadvertently ligated the artery proximal to the right hepatic artery
takeoff by confirming a pulse to the right liver. Once the left
hepatic artery is divided, the underlying left portal vein can be
dissected behind it. A branch to caudate lobe is very constant
and should be preserved if the caudate is not going to be
resected. Proximal dissection and identification of the right
portal vein from the left side is worthwhile to confirm anatomy.
Unless mandated by tumor proximity, we prefer to transect the
bile duct (left or right) intrahepatically during parenchymal transection to absolutely avoid contralateral injury. This is especially
important on the left side where there is often variant drainage
of the major right sectoral ducts to the left hepatic duct.
An alternative to extrahepatic inflow control at the hilum is
intrahepatic control using a pedicle ligation technique. This
technique is most appropriate for right-sided tumors not
encroaching on the hilus. The portal triads carry Glissons capsule with them into the liver substance forming a sturdy pedicular sheath that can be dissected and clamped. Exposure of the
pedicles can be accomplished by parenchymal transection
down to the sheaths or by hepatotomies in the liver substance
above the pedicle. For exposure of the right-sided inflow
pedicle(s), hepatotomies are typically made along the inferior
part of the gallbladder fossa and the caudate process and a
large clamp is used to encircle the inflow structures. The whole
right pedicle can be controlled this way or the right anterior
and posterior sectoral pedicles can be encircled separately. The
approach is rapid and avoids dissection of the contralateral

28

structures in the hilum, but risks injury to the pedicle before


encircling the triad, or hemorrhage from coursing veins, which
commonly run close to the pedicles.
Though total vascular isolation has been employed by some
groups (3538), we have found that total vascular isolation
techniques were not necessary in more than 1800 consecutive
liver resections (2).
Outflow Control
Though there are multiple small veins that drain the right lobe
and segment I directly into the retrohepatic vena cava, the
majority of hepatic blood flow drains into the inferior vena
cava (IVC) via the left, middle, and right hepatic veins. In

Figure 3.4 Sharp and blunt dissection over the suprahepatic IVC exposes the
right, middle and left hepatic veins. Source: Blumgart; Surgery of the Liver,
Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

Left phrenic
vein

Diaphragm

Left triangular
ligament

Diathermy

Figure 3.5 Downward traction on the liver and cephalad traction on the
diaphragm help expose the left coronary ligament. Care must be taken here
to identify the phrenic vein as it courses on the underside of the diaphragm
to enter the IVC, as it can be inadvertently injured if the triangular ligament
is not properly exposed or not divided close to the liver surface. Source:
Blumgart; Surgery of the Liver, Biliary Tract and Pancreas, 4th Edition;
Chapter 80; copyright Elsevier.

HEPATIC RESECTION
major hepatectomy, extrahepatic control of these vessels is
preferred. Standard anatomy consists of a single right hepatic
vein entering the vena cava, and a left and middle hepatic vein
that is joined and entering the cava as a single trunk. Autopsy
studies of the left and middle hepatic venous trunk have elucidated at least five types of hepatic vein trunk variants (39).
The right hepatic vein is typically encircled after the dissection of the vena cava and caval ligament has been carried out
as described earlier. The base of the right hepatic vein should
be dissected sharply and once exposed, a clamp can be passed
between the right and middle hepatic veins. Exposure of the
left and middle hepatic vein extraheaptically can be challenging. The groove between the right and middle hepatic veins is
initially developed from above the liver. The left liver is mobilized and the ligamentum venosum is divided just before its
insertion into the left hepatic vein. Here a tunnel is carefully
developed underneath the middle and left hepatic vein and
they are encircled (Fig. 3.6). It is often difficult to individually
encircle the left or middle hepatic vein extrahepatically but
this depends on the anatomy of the common trunk. It is
important to identify the hepatic venous anatomy on preoperative imaging and recognize variations in the branching patterns,
since bleeding in this area can be difficult to control. Ligation
of the hepatic venous outflow of the liver can also be accomplished during parenchymal transection with careful exposure
of the cava and the origin of these veins once the liver has
been transected to expose them. The exposures for specific
resections are discussed later in the chapter.
Parenchymal Transection
Once vascular inflow and outflow to the lobe or segment has
been controlled, all that remains is division of the liver parenchyma. There are many techniques to accomplish this. The
instruments used are left to the surgeons preference, but it is
imperative that the vessels and ducts divided be identified
and dissected before division. Transection of the liver should
be a deliberate dissection of intrahepatic structures rather
than simply coagulation of liver tissue. In addition to the
ability to confidently ligate each branch on the transection

(A)

line, it allows one to identify the venous drainage and pedicle


inflow to the remnant liver. Moreover, in cases where the
tumor margin is adjacent to major hepatic veins and portal
pedicles, it allows precise extirpation of the tumor. For these
reasons, we prefer a simple crushing technique. Glissons
capsule is scored with diathermy along the transection line
and a Kelly clamp is used to crush the liver tissue and expose
the vessels and ducts for clipping, ligation, or bipolar energy
sealing. Larger pedicles are suture ligated or stapled (40). The
operative surgeon crushes the tissue in small linear planes,
the assistant clips or seals the vessels, and the surgeon divides
the structures. In this fashion, the transection line is quickly
and efficiently completed. Though not always necessary,
inflow occlusion with a Pringle maneuver may be used to
decrease blood loss, and an entire lobe can often be transected with three to four sessions of 1015 minutes on Pringle with 5 minutes off. After removal of the specimen, the
raw surface is carefully inspected for bile leaks, which are
suture ligated or clipped. Some groups advocate injection of
dye or intralipid via the cystic duct to identify open biliary
tributaries for ligation. Since drainage is associated with prolonged hospital stay, increased infection, and no change in a
need for interventional radiology directed drainage, we do
not routinely place drains after hepatic resection in the
absence of biliary reconstruction (41).

major hepatic resection: definitions and


specific considerations
Multiple descriptions of liver anatomy and resections by anatomists and surgeons have resulted in terminologies that can be
confusing and imprecise. A recent consensus conference in
Brisbane, Australia, with the American Hepato-PancreatoBiliary Association has published new guidelines to clarify this
nomenclature. When unclear, or if there is confusion about the
description of a resection, one should revert to naming
the numerical segments involved. The right liver is comprised
of segments VVIII and the left liver is comprised of
segments IIIV. Appropriate terms for resection of the right or
left liver would be hepatectomy or hemi-hepatectomy.

(B)

Figure 3.6 (A) Medial retraction of the left lateral segment exposes the ligamentum venosum. (B) The ligamentum venosum is divided sharply where it is tethered
to the left hepatic vein, releasing the vein and enabling a tunnel to be dissected under the middle and left hepatic veins and anterior to the IVC. Source: Blumgart;
Surgery of the Liver, Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

29

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Extending a right hepatectomy to include segment IV or a left
hepatectomy to include segments V and VIII would be
described as a right/left trisectionectomy or trisegmentectomy. Resection of segments II and III is often referred to as a
left lateral segmentectomy or sectionectomy. There are
essentially five types of major resection. The nomenclature of
these resections is based on the anatomical classification
(Table 3.1) (Fig. 3.7) (4245).
Right Hemihepatectomy (Right Hepatectomy, Right
Hepatic Lobectomy)
A right hemihepatectomy involves excision of segments
VVIII. The right lobe is completely mobilized and the
right hepatic vein is isolated. The peritoneum overlying the
common bile duct and extending into Calots triangle is
incised to expose the cystic artery and duct. These are
ligated and divided. A long tie is left on the proximal cystic
stump and used as a retractor to help expose the common
bile duct and dissect the vasculature. The hilar plate is lowered to protect the left hepatic duct. We typically do not
dissect the right hepatic duct extrahepatically, but address it
during parenchymal transection to absolutely avoid any
potential for injury to the left hepatic duct. The right
hepatic artery usually passes posterior to the common bile
duct (Fig. 3.8) and is sharply dissected, ligated, and divided
to the right of the common duct.
Superior traction on the right hepatic artery stump will
help expose the portal vein. The portal bifurcation is
approached laterally and posteriorly. When dissecting the
right portal vein, care should be taken to identify the first
posterior branch to the right side of the caudate. Circumferential control of the right portal vein should not be
attempted until this branch is identified and dissected as
bleeding from this vein can be troublesome. Once a few centimeters of right portal vein are fully exposed and the left
portal vein has been visualized, it is encircled and divided.
Clamping of the right portal vein at this point should confirm demarcation of the right liver. Occasionally, the right
anterior and posterior sectoral portal vein branches arise
independently from the portal vein. In this instance, they
must be individually dissected and ligated after confirming
flow to the left liver.
The right hepatic vein is isolated and divided as described
previously. It is important that all the retrohepatic veins are
first controlled and divided, that the dissection extends to the

left of the IVC, and that the right hepatic vein is skeletonized
completely right at the liver surface. It is especially important
to gain extrahepatic control of the vein with large tumors near
the hepatic venous confluence or in the posterior sector near
the vena cava, where it can be difficult to obtain tumor clearance without excessive traction on the vein. Alternatively, the
right hepatic vein can also be controlled from within the liver
during parenchymal transection, however, this usually forces
the hepatic transection to the right of the true principal
midliver plane.
After inflow ligation, a line of demarcation becomes evident. Figure-of-eight stay sutures are placed to either side
of this line and parenchymal transection can begin safely.
The surgeons left hand lifts the left lobe from above the
IVC carefully as the transection plane is deepened. This
will expose the middle hepatic vein, and division of the
specimen can proceed to the right or left of the vein
depending on tumor clearance. As the dissection proceeds
superiorly, the segment V and then VIII hepatic veins are
divided along the middle hepatic vein. The main right portal pedicle is exposed and divided with the endo-GIA stapler. This will control the right hepatic duct if it was not
controlled extrahepatically.
Alternatively, an anterior approach can be used to resect
the right lobe of the liver. This approach is advantageous
when the right lobe cannot be mobilized due to a large
right-sided tumor, or there is a large mass adherent to the
diaphragm or IVC (46). In this approach, after extrahepatic
inflow division, the liver is transected without mobilization.
It is then freed from its venous and ligamentous attachments
to the IVC and peritoneum. The parenchyma is transected
from the anterior liver surface to the IVC along the line of
demarcation, and venous tributaries are controlled from the
front, including the right hepatic vein (47,48). To help control bleeding in the deeper parenchymal plane, the hanging
maneuver may be employed (49). In this maneuver, the
anterior plane of the IVC is dissected from the liver undersurface. The most inferior veins draining the caudate are
ligated and divided, and a tunnel is carefully created anterior to the IVC to the space between the right and middle
hepatic veins with a Kelly clamp. This is a blind tunnel of 4
to 6 cm. A tape is passed that can then be used to elevate the
liver away from the anterior surface of the IVC, helping to
define the plane of transection and facilitating exposure of
the deeper tissues. In this technique, the right portal pedicle

Table 3.1 Anatomy and Classification of Major Hepatic Resections


Anatomic Classification
Couinaud

Goldsmith and Woodburne

Brisbane

Segments resected

Right hepatectomy
Right lobectomya
Left hepatectomy
Extended left hepatectomya
Left lobectomy

Right hepatic lobectomy


Extended right hepatic lobectomy
Left hepatic lobectomy
Extended left lobectomy
Left lateral segmentectomy

Right hemihepatectomy
Right trisectionectomy
Left hemihepatectomy
Left trisectionectomy
Left lateral sectionectomy

V, VI, VII, VIII


IV,V,VI, VII, VIIIb
II, III, IV
II, III, IV, V, VIIIb
II, III

Often referred to as trisegmentectomy.


May also include segment I.

30

HEPATIC RESECTION
is divided, parenchymal transection is completed to the
IVC, the lateral venous attachments to the IVC are ligated
and divided, the right hepatic vein is stapled, the coronary
and triangular ligaments are divided, and the specimen is
removed.
Right Trisectionectomy (Right Lobectomy, Extended Right
Lobectomy, Right Trisegmentectomy)
A right trisectionectomy is a right hemihepatectomy extended
to include segment IV. The liver is mobilized as described for a
right hepatectomy. To approach the inflow and outflow of segment IV, the ligamentum teres is elevated to expose the umbilical fissure. If a bridge of tissue between segments III and IV is
present concealing the fissure, this should be divided with
diathermy. Here, the ligamentum teres can be traced to its
embryologic origin at the left portal vein. Incising the fibrous
tissue that tethers the left main pedicle to the base of the
umbilical fissure releases the left-sided structures from the

undersurface of segment IV, and it opens up the fissure. To


safely perform a right trisectionectomy, the left hepatic duct
should be freed clear of the proposed plane of transection.
This is accomplished by lowering the hilar plate as previously
described. The inflow and outflow to the right liver are
controlled and divided as previously described. Once the right
hepatic vein has been divided, the middle vein can usually be
encircled. The liver tissue is divided to the right of the falciform ligament and the pedicles feeding segments IVa and IVb
are ligated and divided as they come off the main left pedicle
(Fig. 3.9). Unless tumor mandates, a deliberate dissection
within the umbilical fissure is usually not necessary. As the
plane of transection is deepened toward the IVC superiorly,
the middle hepatic vein is encountered, dissected, and divided
with a stapler. It is absolutely critical to protect the left hepatic
vein as narrowing or transection of this vein will likely result in
liver failure or massive hemorrhage secondary to a lack of
other venous return from the liver.

(A)

(B)

(C)

(D)

(E)
Figure 3.7 The anatomy and classification of major hepatic resections. (A) right hepatectomy, (B) left hepatectomy, (C) left lobectomy, (D) extended left hepatectomy,
(E) right lobectomy.

31

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

Figure 3.9 To expose and control the portal pedicles to segment IV, the liver
tissue is divided to the right of the falciform ligament and the pedicles feeding
segments IVA and IVB are ligated and divided as they come off the main left
pedicle. Source: Blumgart; Surgery of the Liver, Biliary Tract and Pancreas, 4th
Edition; Chapter 80; copyright Elsevier.

Figure 3.8 During right hepatectomy, the right hepatic artery usually passes
posterior to the common bile duct and is sharply dissected, ligated, and
divided to the right of the duct. After cholecystectomy, retraction of the cystic
duct will expose the underlying artery. Source: Blumgart; Surgery of the Liver,
Biliary Tract and Pancreas, 4th Edition; Chapter 80; copyright Elsevier.

Left Hemihepatectomy (Left Hepatectomy, Left Hepatic


Lobectomy)
A left hemihepatectomy involves excision of segments II
IV. The left lobe of the liver is mobilized, the umbilical fissure is exposed, and the hilar plate is lowered as previously
described. The gastrohepatic ligament is entirely divided,
with care taken to identify any accessory or replaced left
hepatic arteries not identified on preoperative imaging. The
left hepatic artery is dissected at the base of the umbilical
fissure and divided. The caudate branch of the portal vein is
identified before the left main portal vein enters the umbilical fissure. If the caudate lobe is to be spared, the portal
vein is ligated and divided distal to this vein. A line of
demarcation marking the right-sided border of segment IV
corresponds with a plane that usually extends from the IVC
to the base of the gallbladder fossa (Cantlies line). This
principle plane is the same as that seen in a right hemihepatectomy. Segments II and III are reflected medially and
the middle and left hepatic veins are identified, encircled
and divided extrahepatically as described earlier. The left
hepatic vein is often not amenable to circumferential extrahepatic exposure initially but can be exposed after splitting
the liver back to its origin. Parenchymal transection completes the excision.
Left Trisectionectomy (Extended Left Hepatectomy,
Extended Left Lobectomy, Left Trisegmentectomy)
A left trisectionectomy involves removal of segments II,
III, IV, V, and VIII. The entire liver is mobilized. The inflow
and outflow to the left lobe are controlled as previously

32

described for a left hemihepatectomy. The inflow to segments V and VII can be addressed in a few ways. The anterior sectoral pedicle can be encircled intrahepatically either
through hepatotomies or after transection in the right scissura to the left of the right hepatic vein. The pedicle can be
encircled and clamped confirming flow the posterior sector.
Alternatively, an extensive hilar dissection can be carried
out to identify and divide the arterial and portal branches
to the right anterior sector. It is critical that preoperative
imaging is reviewed for anatomic variations in the inflow
and outflow to the right liver. Once the anterior sectoral
inflow is divided, a near horizontal line of demarcation
becomes evident anterior to the right hepatic vein and
dividing the right anterior and posterior sectors. Parenchymal transection continues anterior to the right hepatic vein
and the specimen is removed. The middle hepatic vein is
necessarily taken as part of this resection and is addressed
as described earlier. A left trisectionectomy is a challenging
operation that requires significant experience with major
hepatic resections.
Left Lateral Sectionectomy (Left Lobectomy, Left Lateral
Segmentectomy)
A left lateral sectionectomy involves removal of segments II
and III. The left lobe of the liver is mobilized and the hilar
plate is lowered as previously described. Just to the left of the
umbilical fissure, the portal pedicles to segments II and III are
identified and divided. These can be identified and controlled
through multiple hepatotomies or during parenchymal transaction in a plane just to the left of the falciform ligament. A
deliberate dissection in the umbilical fissure is usually not
necessary. The left hepatic vein is usually divided after parenchymal resection back to its origin but can also be controlled
extrahepatically as described in the outflow control section
of the chapter.

HEPATIC RESECTION

wedge vs. segmental resection


The segmental anatomy of the liver, as defined by Couinaud, divides the liver into eight independent segments, each
with its own inflow and biliary drainage (see chapter 1)
(42,50). As a result, each segment can be individually
resected without affecting the inflow or outflow to the rest
of the liver. Segment-oriented hepatectomy spares normal
parenchyma and is particularly useful when bilateral noncontiguous segments are involved or in patients with
chronic liver disease. Nonanatomic wedge resections can be
useful for small peripheral tumors that are not close to
major inflow pedicles or venous branches for which adequate tumor margins can be obtained. Though some groups
have shown that anatomical resection is not superior to
wedge resection for tumor clearance, pattern of recurrence,
or survival (51), in our experience anatomic segmental
resection resulted in improved tumor clearance and patient
survival compared to wedge resection (52). Wedge excision
may risk fracturing the plane between the tumor and normal liver, margin positivity, and intraoperative hemorrhage (12,53). Anatomic resection may provide better
visibility, decrease the risk of major hemorrhage, and in
many cases provide a wider margin of resection.
Segmentectomy I (Caudate Resection)
The caudate lobe is often resected with a right or left hemihepatectomy, however, isolated caudate resection may be performed for solitary tumors in segment I. The anatomy of the
caudate lobe between the IVC, portal triad, and hepatic veins
can make resection tedious and challenging. The caudate lobe
straddles both hepatic lobes and therefore receives vascular
inflow from both the right and left portal pedicles (54). Venous
drainage is directly into the IVC via one to nine short hepatic
veins (55). The left edge of the caudate fuses with the IVC via
a fibrous band of tissue that encircles the IVC and attaches to
segment VII. In many patients, this caval ligament may be
composed of liver parenchyma.
Dissection at the base of the umbilical fissure exposes the
caudate branches of the left portal vein and hepatic artery
for ligation and division. Segments II and III of the liver
are mobilized and reflected to the right, exposing the caudate where it lies on the IVC. The left lateral attachments
of the caudate to the IVC are divided (56). Exposure and
division of the left caval ligament can be challenging and
care should be taken to avoid injury to the cava inferiomedially and the base of the left and middle hepatic veins
superiorly. With anterior traction on the caudate, the short
hepatic veins draining into the IVC on the posterior aspect
of the caudate can be visualized and controlled. If there is
a bulky tumor in the caudate or anterior traction of the
lobe is difficult, the retrohepatic veins can be approached
from the right side, by mobilizing the right lobe and turning it to the left, then dissecting and dividing all the veins
starting below the caudate and continuing onto the anterior surface of the IVC (57). The caudate branch from the
right portal vein should also be identified and ligated. To
complete the resection, the tissue joining the caudate to
segment VII must be transected. Anteriorly and superiorly,

care must be taken to avoid injury to the middle and left


hepatic veins.
Segments II or III
The approach to excising either segment II or III is the same as
that for a left lateral segmentectomy, except the plane between
the segments needs to be defined. This plane is identified by
the course of the left hepatic vein, segment 3 being anterior
and segment 2 being posterior. Inflow control to either segment is achieved in the umbilical fissure. Ligation of the portal
pedicle will guide resection along the plane of demarcation.
Care must be taken to divide the branches of the left hepatic
vein draining the excised segment, but to leave the main left
hepatic vein intact to drain the remnant liver.
Segment IV
As described in a right trisectionectomy, the inflow to
segment IV is found to the right of the umbilical fissure.
The hilar plate is lowered to protect the left bile duct and to
provide access to the multiple pedicles to segment IV. Ligation of these pedicles will provide a line of demarcation
along Cantlies line. During parenchymal transection, the
venous drainage of segments IVa and IVb are divided
sequentially to the left of the middle vein on the lateral border of the segment, and along the umbilical fissure on the
medial border of the segment, where the umbilical vein
often courses. The middle hepatic vein can be sacrificed in
this operation if necessary with adequate drainage of the
right liver and segments 2 and 3.
Segments V and VIII (Anterior Sector)
The inflow to segments V and VIII are from the right anterior
sectoral pedicle. This can be approached and controlled extrahepatically or intrahepatically as described for a left trisectionectomy. If the anterior and posterior sectoral pedicles branch
within the liver parenchyma, a hepatotomy over the anterior
pedicle is necessary. Alternatively, the liver can be transected
in the principal plane down to the base of the anterior sector
where its origin can be controlled, typically posterior to terminal middle hepatic vein branches. The anterior sector lies
between the right and middle hepatic veins, i.e., between
Cantlies line and a transverse plane anterior to segments VI
and VII. This horizontal plane of transection can be better
defined by clamping the anterior pedicle to demarcate the
right, left, and posterior borders. The transection line between
V and VIII is demarcated and defined intrahepatically when
control of the isolated segmental inflow is obtained. The middle hepatic vein can usually be safely divided in this operation
if necessary, but in the absence of a large accessory right
hepatic vein, the right hepatic vein must be preserved for
adequate drainage of the posterior sector.
Segments VI and VII (Posterior Sector)
The inflow to segments VI and VII are from the posterior sectoral pedicle. This can often be approached and controlled in
the fissure of Ganz, though the anatomy of anterior and posterior pedicles can be highly variable. If the anterior and posterior sectoral pedicles branch within the liver parenchyma,

33

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


the portal pedicles must be approached during parenchymal
transection. The medial plane of transection can be better
defined by clamping the posterior pedicle to demarcate the
border. The classic description of a single pedicle from the
posterior sectoral pedicle feeding either segment VI or VII is
the exception rather than the rule (58), therefore, careful
parenchymal dissection, preoperative study of the CT, and
intraoperative ultrasound are critical to these resections. If a
posterior sectorectomy is to be performed, the right hepatic
vein can be sacrificed since the anterior sector drains into the
middle hepatic vein.
Central Hepatectomy (Segments IV, V, and VIII)
A central hepatectomy with various amount of extension into
any of the three segments can be performed combining the
techniques described above. Typically this requires dividing
the middle hepatic vein intrahepatically near its origin. The
techniques of a segment IV resection and anterior sectorectomy are essentially combined. This is a challenging operation
that requires a substantial surface of liver to be transected but
can be very useful to spare parenchyma while removing centrally placed tumors.

enucleation of benign tumors


see chapters 28, 32, and 33
When indicated, hepatectomy for benign conditions should be
parenchymal preserving. Though anatomic resection along segmental planes is sometimes necessary, some benign tumors may
be enucleated, for example, adenomas, fibronodular hyperplasia, metastatic neuroendocrine tumors, and hemangiomas (2,4).
Hemangiomas in particular push liver tissue away as they grow,
and create a fibrolamellar plane of tissue that defines the border
between cavernous tissue and normal liver parenchyma (2). The
arterial supply to the hemangioma can be determined from preoperative imaging and is clamped, allowing the tumor to
decompress via the venous outflow. The hepatic tissue over the
mass is then incised to enter an avascular plane surrounding the
tumor. Small vessels that traverse this plane are ligated and
divided. The majority of the dissection can be done with the
surgeons finger, and the mass is shelled out. This approach preserves normal parenchyma, eliminates the need for hepatic
venous outflow control, limits blood loss, and has fewer complications than lobectomy (3,4). Management of benign lesions is
covered in further detail in other chapters.

conclusion
Major hepatic resections for benign and malignant tumors can
be accomplished safely and efficaciously. Proper patient selection, precise preoperative imaging, specific anesthetic techniques,
and knowledge of the principal complications are essential.
Study of each patients segmental anatomy will allow inflow and
outflow control and the ability to tailor the resection needed for
each individual.

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34

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51. Zorzi D, Mullen JT, Abdalla EK, et al. Comparison between hepatic wedge
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Radiol Anat 1988;10(1):8391.
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liver. Surgery Gynecol Obstetrics 1990;171(2):1602.
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and VII of the liver based on the ramification patterns of the intrahepatic
portal and hepatic veins. Clin Anat 1999;12(4):22944.

35

Ultrasound for HPB disorders


Duan Li and Lucy Hann

introduction
Ultrasound is the initial study of choice in most clinical situations due to the lack of ionizing radiation, relatively low cost,
and accessibility in varied settings such as at the bedside or in
the operating suite. Ultrasound differs from other crosssectional imaging techniques in that it uses sound propagation
and reflection from interfaces within tissue for imaging.
Images are generated by piezoelectric material within the
transducer that transmits and receives the sound signal. Higher
frequency transducers provide the best resolution, but high
frequencies are attenuated more rapidly in tissue. For that reason, transducer frequency is selected for the application.
Superficial structures are evaluated at frequencies in the range
of 6 to 18 MHz and transabdominal ultrasound, which
requires better penetration, typically uses frequencies ranging
from 3 to 6 MHz.
Doppler is a unique feature of ultrasound for imaging vessels and blood flow. When moving blood is insonated, the frequency of the returning signal is proportional to blood
velocity. A cursor is placed over a specific blood vessel and
images are obtained in both gray scale and Doppler (termed
Duplex scanning). The Doppler information can then be
displayed in three different formats: (1) spectral Doppler, (2)
color Doppler, and (3) power Doppler. Spectral Doppler shows
a waveform with velocity changes and flow direction over
time. Color Doppler displays mean velocities and direction of
flow within vessels. The color codes assigned for velocities are
usually displayed in the upper left aspect of the image. Power
Doppler gives the amplitude of the Doppler signal without
direction or frequency information; since it is not angledependent, it is very useful for imaging low flow and
tortuous vessels.
Ultrasound contrast agents further improve applications for
vascular imaging. Current contrast agents use microbubbles
encapsulated within thin lipid spheres. After intravenous
injection, the microbubbles remain intravascular and do not
diffuse into the interstitium as do MRI and CT contrast agents.
After a low-power ultrasound signal is applied, the microbubbles oscillate (expand and contract) at harmonic frequencies
that are detected by the transducer (1,2). With these ultrasound contrast agents, it is now possible to image tumor vasculature in exquisite detail (37) (Fig. 4.1).
Despite the versatility of ultrasound, there are limitations.
Sound is reflected at bone and air interfaces so scans are
obtained from different positions to avoid intestinal air or rib
artifact. This lack of standardized perspective compared to
axial imaging format of CT and MRI may present difficulty for
referring clinicians who are unfamiliar with the technique. To
lessen bowel gas interference, 6-hour fast is recommended to
improve visualization of the pancreas and liver and to provide
sufficient gallbladder distension. Another significant limitation

36

is that ultrasound is operator-dependent; skilled technologists


and radiologists are essential since diagnosis is made at image
acquisition. For best results, the surgeon should communicate
to the radiologist the specific clinical questions so that appropriate targeted images can be obtained at the time of the
examination.
This chapter will discuss ultrasound applications for diagnosis of hepatic, gallbladder, biliary, and pancreatic abnormalities. The role of specialized ultrasound techniques such as
endoscopic ultrasound and intraoperative ultrasound will also
be addressed.

liver
Anatomically the liver is divided into sectors that are defined
by the scissurae that contain the hepatic veins; these sectors are
then subdivided into individual hepatic segments that each
contain intact portal and arterial inflow and hepatic venous
outflow and draining bile ducts (8,9). Ultrasound hepatic
anatomy is shown in Fig. 4.2.
Diffuse Liver Disease
Diffuse liver abnormalities include fatty infiltration, hepatitis,
and cirrhosis. Hepatic steatosis is present in 17% to 33% of the
general population and in 70% of overweight individuals (10).
On ultrasound, the liver has diffusely increased echogenicity
and in advanced cases significant sound beam attenuation
obscures the deep liver. Areas of focal sparring may be seen
anterior to the portal confluence and adjacent to the gallbladder. Hepatic steatosis impacts perioperative outcome and
accurate preoperative diagnosis would be useful (11). Fatty
infiltration increases liver stiffness, which can be measured by
tissue displacement in response to the transmitted ultrasound
wave. These elastography techniques hold promise for diagnosis of diffuse infiltrative liver diseases such as hepatic steatosis
and early-stage hepatic fibrosis (1214).
Focal Hepatic Lesions
Cystic lesions
Ultrasound is the best modality to differentiate cystic from
solid liver masses and to determine the internal architecture
of cystic lesions. Simple cysts, found in 2% to 3% of patients
(15), have thin wall, no internal echoes, and bright posterior
enhancement. Even if the cyst is lobulated or has thin septation, benign diagnosis can be made (16). Symptomatic large
simple cysts may be treated with ultrasound-guided aspiration and sclerosis (15,17), but it is extremely important to
assess the cyst wall. Mural nodularity, thick tumor rim, and
internal vascularity may indicate neoplasm such as biliary
cystadenoma and these lesions should not be unroofed or
aspirated since complete surgical resection is required. Cystic
liver metastases present as complex cysts often with solid or

ULTRASOUND FOR HPB DISORDERS

(A)

(B)

Figure 4.1 Microbubble contrast enhanced ultrasound image of a hypervascular liver mass. (A) Contrast enhanced image shows the intense hypervascularity of
this liver lesion (arrow) that proved to be focal nodular hyperplasia. (B) The lesion (arrows) is subtle on the corresponding grayscale image. (Complements of
Siemens Medical Solutions, Ultrasound Division. Malvern, PA.)

irregular rim. These are typically from sarcoma, cystadenocarcinomas of the ovary and pancreas, and mucinous colon
carcinoma primaries (16,18). Ovarian metastases are characteristically peripheral implants. Squamous cell tumors with
necrosis appear as cystic masses and other metastases may
cavitate in response to chemotherapy.
The appearance of cyst contents on ultrasound can be used
for differential diagnosis. Pyogenic abscess initially may be
echogenic and later liquified with debris, fluid-fluid levels, and
irregular wall (Fig. 4.3). Echogenic reflections with reverberations, seen in 20% to 30% of cases, suggest air within the
abscess (18). The classic echinococcal cyst is a complex cyst
with well-defined wall, containing double echogenic lines.
Multiple, internal echogenic foci, snowstorm signs settle in
the dependent portions of the cyst. Localized splits in the cyst
wall, with floating, undulating membranes, are also characteristic and the cyst wall may calcify (19,20). Hematomas in the
acute stage may be echogenic and then they have layering lowlevel echoes from blood, and later become honeycombed with
septation. When a preexisting cyst becomes hemorrhagic,
internal septation may be thick and irregular, but they float
freely in real-time and are not rigid.
Solid Liver Lesions
Solid liver lesions are further characterized by lesion echogenicity, vascularity, and peripheral halo. Definitive diagnosis
of benignity can be made for hemangiomas, focal fatty infiltration, and focal fatty sparing because of their classic ultrasound
features. Benign focal nodular hyperplasia can also be identified when the characteristic spokewheel vascular pattern, tortuous feeding artery, and marked hypervascularity are seen on
contrast-enhanced ultrasound or Doppler images (Fig. 4.1).
Hypoechoic liver masses and lesions with a peripheral halo are
suspicious for malignancy. Although CT and MRI are used for
tumor staging, there can be added benefit from ultrasound to

(1) assess lesions that are too small to characterize by CT,


(2) define the relationship of tumor to bile ducts, and (3) evaluate vascular encasement and tumor margin (Fig. 4.4).
Typical hemangioma, seen in 70% to 80% of cases, is a uniformly echogenic mass with sharp margin (21) (Fig. 4.5A). The
multiple vascular interfaces within the hemangioma cause the
increased echogenicity and margin is well-demarcated since
histopathologically hemangiomas lack a capsule. Hemangiomas have absent or minimal flow on Doppler imaging; they are
never hypervascular. Another common appearance of hemangioma is a mass with thin peripheral echogenic rim with mixed
central echogenicity (Fig. 4.5B). Giant hemangiomas > 5 cm
often lack these characteristic ultrasound features because of
central fibrosis, necrosis, and myxomatous degeneration. A
study of 213 patients with typical hemangioma appearance and
without risk for hepatic malignancy found only one patient
with malignancy on long term follow-up and concluded that
typical hemangiomas in low-risk patients do not require follow-up (22). This rule does not apply to patients with cirrhosis,
hepatitis, or chronic liver disease that places them at increased
risk for hepatocellular carcinoma, nor does it apply to patients
who already have malignancies, and particularly not to those
with primary tumors that exhibit echogenic metastases.
Caturelli et al. (23) studied 2,000 patients with cirrhosis. Of
these, 44 had hemangioma-like lesions. On follow-up, half
proved to be hepatocellular carcinomas and half hemangiomas.
Thus, in patients at risk for hepatocellular carcinoma, any
echogenic lesion merits further evaluation or follow-up.
Other benign conditions such as focal fatty infiltration and
focal sparing are diagnosed by geographic margins and typical
location in segment 4 anterior to the portal vein bifurcation or
less commonly, adjacent to the gallbladder. Focal fat appears
echogenic relative to normal liver and areas of focal sparing are
less echogenic than fatty infiltrated liver. A useful finding
on Doppler evaluation is that vessels cross undisturbed

37

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


without displacement through areas of focal fat or focal
sparring (24,25).
A hypoechoic halo around a liver lesion indicates a clinically
significant mass, suspicious for malignancy, including hepatocellular carcinoma and hepatic adenoma and metastases from
colorectal, gastrointestinal, neuroendocrine, renal cell, choriocarcinoma, and vascular primaries such as Kaposi sarcoma
(Fig. 4.4). Pathologically, the halo is caused by proliferating
malignant cells, compression of the liver parenchyma, and
dilated sinusoids. The hypoechoic halo sign has a 95% positive
predictive value and an 87% negative value for differentiating

metastases from hemangioma (26,27). A hypoechoic halo may


be seen even in small lesions <1.5 cm. The halo is detected
when the tumor is hyperechoic relative to the surrounding
liver. In hypoechoic tumors, the lesion and the halo have the
similar echogenicity and therefore the halo sign is not evident.
Hepatocellular carcinoma (HCC) has a variable sonographic
appearance ranging from hypoechoic to echogenic, but a
hyperechoic lesion with hypoechoic halo is the common presentation. Small satellite tumors are typically hypoechoic.
Doppler evaluation is the key in diagnosing HCC since the
tumor is hypervascular and invasion of the portal or hepatic

(A)

(B)

(C)

(D)

(E)
Figure 4.2 Normal liver anatomy. (A) Transverse view of the right lobe. The middle hepatic vein separates the right from left hepatic lobes. The right hepatic vein
divides the right anterior sector (segments 8 and 5) and the right posterior sector (segments 7 and 6). R = right hepatic vein, M = middle hepatic vein, IVC =
inferior vena cava. (B) Longitudinal view of the right lobe reveals the right hepatic vein RHV and the hepatic segments. RK = right kidney. (C) Transverse view of
the portal vein bifurcation. Segments are numbered. R = right portal vein, L = left portal vein, RK = right kidney, IVC = inferior vena cava, A = aorta. (D) Longitudinal view of the left lobe. The left hepatic vein separates the posterior left sector segment 2 from the anterior sector (segments 3 and 4). The caudate, segment 1,
is demarcated anteriorly by the fissure for the ligamentum venosum (arrowhead) and the inferior vena cava posteriorly. IVC = inferior vena cava. RPV = right
portal vein. (E) Color Doppler sagittal image of the portal vein reveals hepatopetal flow.

38

ULTRASOUND FOR HPB DISORDERS


veins is very common; about 40% of patients have portal
venous involvement and 25% show hepatic venous involvement (28). Flow within the tumor is usually of high velocity
and low resistance due to arterial-venous shunting within the
tumor. Tumor thrombus from HCC can be distinguished from
bland thrombus when arterial flow is detected within the

thrombus (29). With ultrasound contrast agents, the hypervascularity and dysmorphic vessels in HCC are more apparent
and there is washout in the portal venous phase.
Hypoechoic liver masses are suspicious for malignancy.
Liver metastases that are hypoechoic are most commonly from
breast, lung, esophagus, stomach, pancreas, and non-Hodgkin
lymphoma.

gallbladder and bile ducts

Figure 4.3 A 50-year-old woman several years postpancreaticoduodenectomy


for duodenal carcinoid developed fever after hepatic artery embolization for
control of hepatic metastases. Right hepatic liquified abscess (asterisk) with
posterior acoustic enhancement (arrowhead). Small posterior solid metastases
(small arrows) are also seen.

(A)

Ultrasound is the procedure of choice for evaluation of the


gallbladder and bile ducts. Gallstones are mobile, echogenic,
and have posterior acoustic shadows (Fig. 4.5). The shadowing is present with or without gallstone calcification; it is
due to the acoustic mismatch between stone and surrounding bile. Stones <3 mm may not generate a shadow because
of small size. Gallstones move quickly with positional variation in contrast to sludge, which moves slowly and lacks an
acoustic shadow. Gallbladder polyps do not shadow and
they are fixed in position. Management of gallbladder polyps depends on size and sonographic appearance. Cholesterol polyps, usually <5 mm and multiple, do not progress as
shown in long-term studies, but larger polyps 1 cm or
greater or those with irregular margins are at risk for malignancy (30,31).

(B)

Figure 4.4 Colorectal metastasis to left hepatic lobe was evident on ultrasound but not by CT done the same day. (A) The lateral left lobe was considered negative
on CT. (B) Longitudinal ultrasound revealed a segment II metastases with peripheral halo (calipers) consistent with malignant lesion.

(A)

(B)

Figure 4.5 Hemangioma. (A) Typical hemangioma (arrow) is uniformly echogenic with no surrounding halo. (B) An atypical hemangioma with a thin bright rim
(arrow) is shown in this longitudinal view of the right hepatic lobe. Another hemangioma (arrowhead) is noted peripherally.

39

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Normal gallbladder wall thickness is <3 mm. Mural thickening may occur with adenomyomatosis, inflammation, or neoplasm. Adenomyomatosis may be focal mass (adenomyoma)
or diffuse thickening and gallbladder deformity with hourglass configuration. Ring down artifact from cholesterol crystals in AschoffRokitansky sinuses is a diagnostic ultrasound
feature of adenomyomatosis. Acute cholecystitis causes diffuse
or focal gallbladder wall thickening with a layered appearance
and in severe cases, the sloughed mucosa may be seen (Fig. 4.6).
Marked edema in the pericholecystic space may mimic
acute cholecystitis in patients with pancreatitis or hepatic
inflammation.

(A)

It is essential to carefully evaluate the gallbladder wall to


exclude gallbladder carcinoma that may coexist with stones
(Fig. 4.7). This is particularly important in patients being considered for laparoscopic cholecystectomy since surgical management of gallbladder carcinoma usually requires hepatic
resection and recurrences in laparoscopic port sites are frequent (32). Gallbladder carcinoma may cause focal thickening
or may obliterate the gallbladder lumen. Associated tumor
extension into hepatic segments 4 and 5 and biliary obstruction at the hilus are common.
Ultrasound is sensitive for detection of biliary dilation and
to determine level of obstruction. Dilated intrahepatic bile

(B)

(C)
Figure 4.6 Acute cholecystitis in a 56-year-old woman with abdominal pain. (A) Longitudinal view reveals a laminated appearance to the anterior gallbladder wall
(arrowheads) and gallstone (arrow) with posterior acoustic shadow. (B) Transverse view shows thickened wall at 6 mm (calipers). (C) Longitudinal color Doppler
image reveals vascular flow within the gallbladder wall.

(A)

(B)

Figure 4.7 Gallbladder carcinoma. (A) Longitudinal and (B) transverse sonogram of the gallbladder reveals a stone (arrowhead) with acoustic shadowing. The
anterior fundus is narrowed and surrounded by hypoechoic soft tissue that infiltrates the adjacent liver (arrows).

40

ULTRASOUND FOR HPB DISORDERS


ducts produce the double duct sign and dilation of the common bile duct >6 mm is considered abnormal. There has been
controversy regarding the size of the common bile duct with
increasing age and postcholecystectomy, but recent studies
have shown that even in the elderly, 98% of ducts are <6 mm
and there is no compensatory dilation of the common duct
after cholecystectomy (3336).
Cholangiocarcinomas cause biliary obstruction in characteristic patterns. Intrahepatic cholangiocarcinoma arises from the
peripheral bile ducts and bile duct obstruction peripheral to
the tumor is seen in almost one third of the cases. These tumors
are also typically hypovascular, in contrast to HCC. Hilar cholangiocarcinoma are typically smaller since their critical location produces early jaundice. Associated vascular encasement is
evident in nearly 50% of the cases (37). Ultrasound is useful for
tumor staging that is determined by location of tumor along
the ducts and the extent of vascular involvement (38).

pancreas
The echotexture of the normal pancreas is uniform and slightly
higher echogenicity than liver. With aging and obesity, fatty
infiltration of the pancreas may further increase echogenicity.
The pancreatic duct is best seen transversely and is normally
less than 2 mm in the body and 3 mm in the head (39).
Diffuse Pancreatic Diseases
In acute pancreatitis, the pancreas may become enlarged and
hypoechoic with indistinct margins from edema. The edema
may involve the entire gland or only a portion, usually the
head. Peripancreatic fluid is a useful diagnostic feature; fluid
and vascular mural thickening may also be observed (40)
(Fig. 4.8). Pancreatic duct may be dilated. In the most acute
stage, ileus limits ultrasound visualization and CT is more useful, but ultrasound has a role to exclude biliary calculi as an
etiology for the pancreatitis (4144). Severe inflammation
progresses to inflammatory pancreatic mass or phlegmon with
fluid collection, hemorrhage, and necrosis. Fluid is commonly
seen within the lesser sac, anterior pararenal spaces, transverse
mesocolon, small bowel mesentery, and parapancreatic spaces
(45). Pseudocysts may persist for a minimum of 4 weeks after

Figure 4.8 Acute pancreatitis in a patient with AIDS. Transverse sonogram of


the pancreas reveals heterogeneous pancreatic parenchyma and edema of the
splenic vein (arrow). The vein has a layered appearance with a ring of
hypoechoic fluid within the wall of the vessel. Fluid also is seen in the peripancreatic space (arrowheads).

the onset of pancreatitis (46). Identification of infected pseudocyst is limited, but the presence of echogenic foci corresponding to gas bubbles is suggestive of infection. If there is
clinical suspicion, ultrasound can provide image guidance for
fluid aspiration or drainage. Venous thrombosis and pseudoaneurysms that occur secondary to pancreatitis can also be
evaluated sonographically.
Ultrasound findings in chronic pancreatitis include alteration of texture, calcification, pancreatic duct, and/or bile duct
dilation, and chronic pseudocyst. The gland is usually atrophic
and heterogeneous. Calcification, either focal or diffuse, and
pancreatic duct dilation are the most classic sonographic features (47). When findings of chronic pancreatitis mimic neoplasm with ductal dilation, CT or MRI is needed to make the
distinction.
Pancreatic Neoplasms
Characterization of pancreatic masses, aspiration and biopsy
are increasingly being done with endoscopic ultrasound
(EUS). Miniature ultrasound transducers mounted on endoscopes display radial or linear images of the pancreas. EUS is
more sensitive for detection of small masses and biopsy can be
performed through the posterior gastric wall (48).
Adenocarcinoma appears on ultrasound as a focal mass with
atrophy and pancreatic duct dilation distal to the mass. Vascular invasion is frequent and bile ducts are dilated commonly
for masses in the pancreatic head. Ultrasound is considered
reliable for diagnosis of nonresectable tumors and in such
cases further imaging is not required; evaluation can proceed
directly to biopsy for tissue diagnosis (40,49) (Fig. 4.9). Staging of pancreatic adenocarcinoma by EUS and CT were compared in a prospective study by DeWitt (50). EUS had higher
sensitivity than CT for tumor detection (98% vs. 86%), better
staging accuracy (67% vs. 41%), and both techniques were
equivalent for nodal status. EUS is also useful for biopsy especially when CT-guided biopsy is negative. In a prospective
study of patients with negative CT-guided biopsy of pancreatic masses, EUS biopsy had 95% sensitivity and 100% specificity for diagnosis (51).
Neuroendocrine tumors such as insulinomas and gastrinomas usually have classical symptoms. When tumors are small,
abdominal ultrasound is limited, but laparoscopic ultrasound
and intraoperative ultrasound are extremely useful for tumor
detection (52,53). Approximately one-third of endocrine
tumors are nonfunctioning and these tumors are more likely
malignant.
Cystic pancreatic neoplasms (serous microcystic adenomas,
mucinous adenomas, and solid and cystic pseudopapillary
tumors) are best evaluated with EUS. Serous microcystic adenomas are benign tumors with multiple cysts ranging in size
from 1 mm to 2 cm. These tumors may appear solid on ultrasound because of numerous interfaces produced by the microscopic cyst walls (5457). Macrocystic mucinous tumors of the
pancreas are malignant or potentially malignant and have
cysts >2 cm. The cysts may have thick septation, mural nodules, and calcification may be present (47,56). It is not possible
to distinguish between benign and malignant mucinous
tumors, but in general, larger cysts and cystic masses with

41

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

(C)
Figure 4.9 Unresectable pancreatic adenocarcinoma. (A) Longitudinal ultrasound image of the pancreas shows an enlarged pancreatic head (m) and dilated common bile duct (arrow), PV = portal vein, IVC = inferior vena cava. (B) Transverse sonogram reveals the pancreatic head mass (m) and dilated pancreatic duct
(arrows) anterior to the splenic vein (SV). IVC = inferior vena cava, a = aorta. (C) Transverse sonogram reveals a left hepatic metastasis (arrows). R = right hepatic
vein, M = middle hepatic vein, IVC = inferior vena cava.

significant solid component are more likely to be malignant


(47,55,58). Aspirates of cystic lesions are relatively acellular
but fluid analysis for tumor markers is useful. Brugge et al.
(59) reported that elevated cyst fluid CEA level had 79%
accuracy for diagnosis of mucinous tumors.

intraoperative ultrasound
Intraoperative ultrasound (IOUS) is an important tool for (1)
assessment of tumors at the time of resection, (2) vascular mapping during hepatic resection or live split liver donor transplantation, and (3) guidance during intraoperative tumor ablation
or biopsy (6064) (Fig. 4.10). During hepatic resection, IOUS is
used to characterize liver lesions that are indeterminate or occult
on preoperative imaging. IOUS can accurately assess tumor
extent relative to vascular structures and bile ducts (6568); this
is important since approximately 1 to 2 cm margin should be
available between the tumor and vessels for optimal surgical
outcome and vessel encasement or thrombosis may alter surgical approach (6972). A prospective study by Cerwenka et al.
(73) evaluated the role of IOUS in patients who had partial hepatectomy after standardized hepatic protocol preoperative MRI.
Small additional lesions with mean size of 1.5 cm were found by
IOUS in 7% of patients and in 5% of patients IOUS findings
altered surgical strategy (73,74). IOUS altered management in
20% of patients who had resection for primary or secondary
hepatic malignancies. Even with recent improvements in crosssectional imaging, there was no significant difference in resection

42

rate (72%), detection of unrecognized additional tumors (20%


vs. 14% p=0.70), or detection of vascular involvement when
groups in the years1999 to 2003 and 2003 to 2005 were
compared (68,7476).
Special dedicated high-frequency (510 MHz) transducers
are required for IOUS; these transducers can be applied
directly on the area of interest to improve resolution compared to transabdominal ultrasound, which is limited by distance and abdominal wall artifact. Typically IOUS probes are
small T-shaped linear and hockey-stick-shaped probes, which
are easy to manipulate within restricted operative fields.
Transducer specifications should include good near field resolution and Doppler capabilities. It is preferable to have the
scanner connected to the hospital network to provide (1)
access for consultation at remote sites during real-time scanning and (2) permanent image archiving in the electronic
record.
Review of preoperative imaging is essential before IOUS since
preoperative planning increases the efficiency of the procedure.
While performing IOUS, the surgeon should avoid applying
excessive pressure. If vessels become compressed, it is difficult to
assess patency or encasement. Light touch with the transducer
can be used as a palpation method to differentiate between soft
benign lesions such as hemangiomas, focal fat, and fat sparing
versus malignant lesions, which are usually firm (77,78).
IOUS may be limited for lesions in the high right lobe or in
the posterior subdiaphragmatic location where access is

ULTRASOUND FOR HPB DISORDERS

(A)

(B)

(C)
Figure 4.10 Intraoperative ultrasound reveals additional hepatic lesions. (A) A 2 cm segment 7 liver lesion (arrows) with peripheral halo and (B) an 8 mm
segment 6 lesion (arrow) were seen on preoperative imaging. (C) A nonpalpable 6 mm lesion (arrow) in segment 4A was not evident on preoperative imaging.
Lesions were resected with diagnosis of metastatic neuroendocrine carcinoma; primary site later identified in the pancreas. (Complements of Robert A. Kane,
M.D., Professor of Radiology, Harvard Medical School, Chief, Body and Abdominal Ultrasound Imaging, Beth Israel Deaconess Medical Center, Boston, MA.)

difficult. In that situation, scanning from the opposite surface


of the liver may improve visualization. Artifacts in the near
field of the image may also obscure lesions near the hepatic
surface. If this occurs, the surgeon can immerse the liver in a
sterile saline bath, thereby changing the focus zone to better
visualize the superficial anatomy. Another difficulty may be
encountered when attempting to visualize lesions near a surgical margin. Echogenic foci from air bubbles in the parenchyma
after cauterization or radiofrequency ablation may mimic
echogenic mucin-containing colorectal metastases. This pitfall
can be mitigated by imaging before intervention to accurately
determine number, size, and location of lesions (7981).
New advances in intraoperative and interventional ultrasound techniques now allow fusion of ultrasound, CT, and
MRI images and electromagnetic tracking to more precisely
localize lesions for biopsy and thermal ablation procedures.
For example, after initial CT data is entered, information
from electromagnetic sensors is applied onto the needle
device and the patient can guide the needle track in real time
even when the needle is out of the ultrasound imaging plane.
This process brings two data sets into spatial alignment. Such
techniques have shown improved needle tracking for

interventional procedures and better three-dimensional visualization of tumor and treatment zone during radiofrequency
ablation (63,8284).

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45

Liver surgery in elderly patients


Gerardo Sarno and Graeme J. Poston

introduction
The recent increase in the geriatric population in society and
increased life span have raised the expectation from surgeons
to expand their operative indications to include geriatric
patients. In liver surgery, the indications for hepatectomy have
been expanded to include patients aged 70 and older, and several studies have demonstrated acceptable long-term survival
of elderly patients after such surgery (1,2). In 1937, Brooks
reported the results of surgery for 287 patients aged 70 and
older. The operative mortality rate was high (19%), and onethird of patients who had abdominal operations died in hospital. Nevertheless, the author emphasized that with the rapid
growth of the elderly population, and prolonged life expectancy, surgeons will increasingly be confronted with surgical
problems among the elderly and must therefore strive to
improve their results by studying physiologic processes in the
aged (2,3). In the seven decades since Brooks paper, advancements in anesthesiology and intensive care, an increased
knowledge of liver physiology, surgical hepatic anatomy, and
resection techniques have encouraged hepatic resection in
elderly patients, achieving improved surgical outcomes.
Because of the high prevalence of liver cancers and aging of
the world population, the elderly population considered for
liver resection has increased (4,5). Also an effective multidisciplinary approach and better selection of elderly patients leads
to reduced age-related perioperative morbidity and mortality
(6). Moreover, the definition of elderly patients has been better defined so avoiding unnecessary confusion that has generated over the past years.
Although advances in minimally invasive ablative techniques
have increased the treatment options for patients with malignant hepatobiliary disease, liver resection remains the only
treatment demonstrated to offer long-term survival (79). Also
the past three decades have seen a dramatic decline in the mortality rate after liver resection in selected elderly patients, which
is less than 5% in tertiary cancer care referral centers (2,6,10).
Colorectal cancer has become a major public health problem that increasingly affects older people (11), and because the
liver is the most common site of metastases, the number of
elderly so affected is increasing (12). Liver resection is also successfully performed in aged patient suffering primary malignancies such as hepatocellular carcinoma (HCC) with results
comparable to those seen in younger people.
In this chapter, we highlight the main advances performed
in liver surgery, taking into account all the issues that are still a
matter of debate for elderly patients with primary or metastatic liver disease.

definition of elderly patients


The age at which persons become elderly depends on social,
environmental, and individual factors. Nowadays, after years
46

of arbitrary definition of elderly, in liver surgery the common practice is to identify as elderly a patient older than
70 years (6,1318). This is due to the evidence of a rapid
decrease of liver mass and portal blood flow from 70 years
onward (17), which may affect liver function.
A limited life expectancy in the elderly might argue against
extending the indications for hepatectomy in these patients.
However, life expectancy for people aged between 80 and
85 years is still 8 years, and 6 years for those over 85 years old.
Moreover, the risk of cancer-related death diminishes with
increasing age; it is estimated to be 40% for those aged between
50 and 70 years, falling to 10% for those over 90 years old (19).
Recently, several studies reported comparable early and
long-term results between young and aged patients undergoing liver resection. These studies highlighted that an age limit
does not exist to contraindicate liver resection. After a careful
evaluation of the operative risk, a similar chance of long-term
survival can be offered also to well-selected elderly patients.

age-related liver changes


The effects of aging on the human liver have not been clearly
determined (20). In general, aging is characterized by a progressive decline of cellular functions and also the liver undergoes physiological changes. Although some recent studies have
shown that aging itself does not affect liver function, the
amount of hepatic tissue that can be safely removed, and the
consequent capacity of liver regeneration are often difficult to
be precisely assessed (14).
Aging has been shown to be associated with multiple changes
in hepatic function, however the clinically relevant biochemical parameters of liver function remain generally normal in
the elderly. Thus abnormalities of these parameters should be
evaluated for the presence of liver disease (21). As a matter of
fact, the liver function seems to be quite well maintained in old
age, but numerous age-related changes in hepatic structure
have been described (22).
However, there have been few comprehensive studies of liver
morphology during aging, and most of these have been performed in rodents (20). The most frequently cited morphological change in the human liver is a decrease in size. In elderly
men, liver weight declines by about 6.5% and in women it
decreases by 14.3% (23), which may be attributable to decreased
hepatic blood flow (2426). The decrease in blood flow is about
45% in subjects over 75 years when compared to those under
40 years (26,27). The classic gross appearance of the liver in
older persons is known as brown atrophy. The brown color is
due to accumulation of lipofuscin (ceroid) within hepatocyte
and also associated with major degree of steatosis (21). Alteration in the hepatocyte morphology has been also described
(28). It has been reported that the liver in elderly humans has
histologically fewer, but larger hepatocytes (29).

LIVER SURGERY IN ELDERLY PATIENTS


In addition, hepatic clearance of many drugs is reduced in
elderly persons (20,22). Traditional theories have attempted to
attribute this observation to age-related reduction in liver
mass and blood flow (2426). More recently, it has been considered attributable to age-related changes in the sinusoidal
endothelium and space of Disse, which may restrict the availability of oxygen and other substrates (30). Several other
mechanisms have been described, among them the impaired
enzymatic activities (31,32) due to oxidative protein damage
sustained by free radicals (21).
The rate of hepatic steatosis allowing safe liver surgery is not
yet clearly defined, although a moderate to severe steatosis
(involving more than 30% of the hepatocytes) seems to affect
both postoperative morbidity and mortality (33,34). However,
although it is impossible to exactly predict this feature before
surgery without a liver biopsy specimen, this diagnostic tool
should be considered when the presence of steatosis is suggested by imaging and a major resection is planned (14).
All of these factors may reduce the functional reserve of the
organ and therefore predisposing to postoperative liver failure
(35). Thus in preoperative risk estimation prior to hepatic
resection, it may be important to take into account the effect
of aging upon liver function and structure, in addition to carrying out a qualitative and quantitative evaluation of liver
parenchyma.

evaluation of the surgical risk


The stress of liver resection may not be well-tolerated in the
elderly (4). Liver surgery is not without complication and,
before considering liver resection in elderly patients, the
increased risks and costs of such surgery must be balanced
against the potential improvement of life expectancy. Elderly
patients are more likely to have decreased life expectancy with
comorbidity, so the decision to perform major hepatectomy
has to be carefully balanced against the likelihood of benefit
before undertaking such resections. However, most studies
record small numbers of cases or have not distinguished
between major and minor resections, making interpretation of
results difficult (32).
Factors other than age should be considered in evaluating
surgical risk in the elderly.
It is well known that in elderly patients, a preoperative
decline in cardiac and pulmonary functions, also combined
with cerebrovascular disease can be frequently seen (2,36). To
achieve better results in the elderly population, proper patient
selection in terms of liver functional reserve and comorbidities
conditions is mandatory. This necessitates a close collaboration between surgeons, anesthesiologists, cardiologists, pulmonary physicians, and geriatric physicians (6). A clear
preoperative selection process should be undertaken to minimize perioperative risks (37).
The majority of elderly may suffer from more than one
comorbid disease or for many reasons do not have a good performance status. Cardiovascular and pulmonary disease have a
prevalence among the elderly of 20% to 27% and 14%, respectively (38). Moreover, cardiovascular disease and diabetes mellitus were reported to be significant risk factors especially
when associated with cirrhosis (3941).

The most frequently reported causes of death in elderly


patients with no underlying liver disease undergoing liver
resection are hepatic insufficiency, myocardial infarction,
pneumonia, and gastrointestinal bleeding (4,42,43).
The evaluation of associated medical disease has been widely
investigated focusing in particular on American Society of
Anesthesiology (ASA) scores. Advanced ASA grading is known
as one of the most reliable predictors of postoperative complications and mortality (4). ASA scores measure major comorbid diseases easily and with minimal expense and are able to
predict outcomes after major surgical procedures (4,44).
Some authors have considered an ASA score higher than II
(i.e., a patient with mild to moderate systemic disease) as a
contraindication for surgery for HCC or for major hepatectomies (42,45). In such patients procedures other than surgery
(radiofrequency ablation or transarterial chemoembolization)
could be considered (16).
The exact determination of the ASA score is highly operatordependent and the reported experiences of postoperative deaths
for causes unrelated to surgery (i.e., myocardial infarction) (42,46) in subjects with an unremarkable history of cardiac
or pulmonary disease suggest that this score should be applied
more selectively during the evaluation of elderly patients with
underlying liver disease (14). Also in the elderly, the performance status, especially if they were physically active before surgery, has to be taken into account since a significant lower risk of
postoperative complications have been recorded (47).
Finally, the morphologic characteristics of the underlying
liver pathology and number and size of malignancies have to
be carefully evaluated prior to performing hepatectomy, aiming to avoid overextensive resections and to minimize intraoperative haemorrhage (6). One other factor having deleterious
effects on early and late outcome is intraoperative blood loss.
It is well known that hemorrhage and the need for transfusion
are closely associated with worse prognoses (48), and this may
be even worse in an aged liver.

colorectal liver metastases


Colorectal cancer is a major public health problem. In western
society, it is expected to increase in incidence by over 30% over
the next 20 years because of ever-growing elderly (>70 years of
age) population (49,50). The liver is the most common site of
metastases and is involved approximately in half of patients
(12). By the time of initial diagnosis of colorectal cancer, nearly
a quarter of patients will have clinically detectable liver metastases (CRLM), despite increasing patient and clinician awareness of the disease. Of those who undergo apparently successful
resection of the primary tumor, nearly half will develop liver
metastases, usually within the first three years after colectomy (49,51,52).
Currently, over half of all cancers are diagnosed in elderly
patients, and 76% of all colorectal cancer patients are diagnosed between 65 and 85 years old (53,54). Encouraging
results of surgery for CRLM in the elderly have been reported
with 5-year survival rates between 21% and 44% (2,4,5558).
In elderly patients, liver resection for CRLM provides, as
with younger patients, the only chance of cure, compared with
untreated patients who have a median survival of 4.5 to

47

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


6.5 months (59,60), or patients treated by chemotherapy alone
who have a median survival of 9.2 to 16.5 months (60,61). The
only true contraindication for liver resection is the technical
nonfeasibility of hepatectomy, independent of the presence of
other poor prognostic factors (8,62).
In 2005, the reported percentage of patients over 70 years of
age undergoing liver resection for CRLM was 26.5%, which was
dramatically higher when compared to 6% in the early 1990s
(6). This improvement is mostly related to developments in
liver surgery since resection for CRLM can be performed with
a mortality rate below 5% (6,13), with 5-year survival rates
ranging from 28% to 39% (4,7,63,64). Better results can now
also be achieved because of the extensive use of chemotherapy
in the elderly. Elderly patients can receive protocols similar to
younger ones (65). In general, since the introduction of oxaliplatin into chemotherapy regimens, a prolonged survival and a
delay of progression of disease has been reported (13,66,67).
The main issue of the use of oxaliplatin is hepatotoxicity (sinusoidal congestion and thrombosis), which could also prove to
be a problem, especially in case of impaired liver function
(13,68). However, no significant postoperative complications
have been reported in elderly patients who did or did not
receive chemotherapeutic treatment (13).
Further evidence for offering hepatic resection to well-selected
older patients is the evidence of similar benefit provided by
repeat hepatectomy to elderly and younger patients (6).
Liver failure is a worrying but thankfully rare complication
after liver resection. Some authors have found elderly patients
to be more at risk of developing this complication than younger
ones, resulting in a more conservative surgical selection policy
(69,70). Severe postoperative liver dysfunction may be present
in fewer than 10% of elderly patients who have undergone
major liver resection for malignancy (71). Postoperative liver
failure due to large resections or sepsis is the most frequent
cause of death (71). In general, liver resection should be avoided
in the presence of bilobar or need for extended resections, especially when associated to concomitant extrahepatic disease and
in medically compromised patients. In those cases, the indication for surgery should therefore be very carefully considered
only in selected cases (6,72). In view of these findings, it is
advisable to consider limited resection whenever possible from
the oncologic perspective rather than extended surgery.
The existing surgical literature on surgery for CRLM in
elderly patients (2,4,5558) should be interpreted with caution because of the small patient numbers treated at single
centers. Often these series describe less than 50 patients. Only
recently a large cohort study, collecting data from more than
100 centers, has been published (6). This study highlighted the
evidence that hepatic resection for CRLM can be performed
safely in elderly patients provided they are fit for such a procedure. The difference in survival between elderly and younger
patients could in part be explained by the more limited survival expectancy of the elderly population, also reflecting the
higher prevalence of comorbidity.

hepatocellular carcinoma
Primary tumors of the liver are among the most common
solid tumours worldwide (4).

48

The incidence of HCC is the fourth highest among all


tumors (18), the number of patients affected has been increasing (73), and the age for detection of HCC is increasing in
both men and women (17). Clarification of the optimal treatment strategy for extremely elderly patients with HCC has
thus become an urgent necessity. Management of HCC with
other modalities, such as percutaneous ethanol injection therapy (74), microwave therapy (75), and percutaneous radiofrequency ablation (RFA), may be an acceptable alternative to
hepatic resection in the elderly, but the best treatment for
patients in this age group remains controversial.
Liver transplantation is theoretically the optimal treatment
for HCC because it is the only method of treating both the
tumor and the underlying liver cirrhosis. Replacement of the
diseased liver is not only the best oncological treatment, but
also the best method for preventing the development of new
tumors and avoiding the life-threatening complications of cirrhosis. In patients with HCC and cirrhosis, transplantation
based on the Milan criteria achieves a better outcome than
hepatic resection with respect to both survival and disease
recurrence (7679). However, the limited availability of donor
organs makes liver transplantation problematic (80,81) and as
a consequence patients older than 70 years are excluded from
transplantation programs (82).
With advances in surgical treatment for HCC, hepatectomy
for elderly HCC patients has become safer. There have been
many reports of hepatectomies for elderly HCC patients
(8385). But because of the unclear data on long-term survival
after local ablation of HCC, especially for large tumors, liver
resection remains the preferred treatment, with 5-year survival
rates ranging from 40% to 50% (86,87).
Resection is considered to be a reasonable first-line treatment for patients with small tumors and underlying chronic
liver disease, which may offer potential cure (80).
Recent studies have shown the safety and feasibility of hepatectomy for HCC patients older than 70 years of age (88,89). It
has been demonstrated that long-term outcome after resection
of HCC is similar in older and younger patients (1,10,83,85).
No operative mortality has been reported in a series of carefully selected octogenarians who underwent liver resection for
HCC (45).
Recent studies have identified some differences in the clinical
pathological features of HCC between elderly and younger
patients. Risk factors for HCC seem to be different in elderly
people. A significant lower positive rate for HBsAg has been
described among the elderly (88,90). Most HBV-related HCCs
develop in patients in their early fifties. This may be the reason
why there are few elderly HCC patients with HBV infection. On
the other hand, HCV infection constitutes a major part of the
etiology in elderly patients with HCC (17,91). Factors other
than viral hepatitis infection, such as alcohol or genetic mutations, may contribute to the development of HCC in some
elderly patients (88). Several studies have shown that elderly
patients with HCC had good liver function and that only a
small percentage of elderly patients with HCC had liver cirrhosis (90,92). It is possible that a large proportion of patients with
cirrhosis and HCC die before reaching the age of 70 years, and
those who survive have well-preserved hepatic function (93).

LIVER SURGERY IN ELDERLY PATIENTS


Some studies have demonstrated a close relation between
HCC and alcohol abuse, that is, individuals who abuse alcohol
have a significantly higher relative risk of developing HCC
than those who do not. Although data about the role of alcohol in the development of HCC are inconsistent, the mechanisms that have been proposed include the induction of
tumorigenesis secondary to alcoholic cirrhosis, a direct tumorinitiating and promoting effect of ethanol through induction
of various enzymes, alterations of DNA repair, dietary deficiencies, immune suppression, and depletion of hepatic antitumor factors (17).
There is no general agreement about the relation between
alcohol abuse and postoperative recurrence of HCC or survival, but there have been a few reports of an interaction
between alcohol abuse and postoperative recurrence (94). The
mechanism by which alcohol abuse is related to HCC recurrence and a lower survival rate remains to be elucidated. However, at least two possible reasons can be suggested for the
higher postoperative recurrence rate in patients with alcohol
abuse. First, these patients may be more susceptible to developing new primary tumors after hepatectomy because chronic
alcohol abuse enhances hepatocarcinogenesis. Second, they
might have a higher incidence of unrecognized intrahepatic
metastases at the time of initial hepatectomy because chronic
alcohol abuse seems to be related to the aggressiveness of HCC,
including the rate of metastasis (17).
Heavy alcohol abuse and HCV infection are two leading
causes of cirrhosis (91). Preoperative severe liver dysfunction
carried a high risk for postoperative hepatic failure, and cirrhosis is associated with increased postoperative mortality in
general (71).
Advanced age is still related to poor early outcome (42), with
operative mortality rates of up to 42%, attributable to liver
failure in patients with cirrhosis (95). The significance of AFP
has still not been well-defined. Some authors found a lower
frequency of raised AFP level, compared with younger
patients (17).
Various other predictors have been reported to be risk factors for poor prognosis of postoperative HCC patients, such as
liver cirrhosis, ChildPugh grading, tumor size, satellite nodules, and vascular invasion (18).
Some authors found a significantly higher frequency of
tumor encapsulation in elderly HCC patients when comparing the histological characteristics of the resected tumors.
Tumor encapsulation has been reported as a favorable prognostic factor for HCC (96). Also a higher frequency of tumor
encapsulation might be an indicator for less malignant degree
of the elderly patients with HCC (18).
Tumor diameter should not be considered a prognostic factor. Patients over 70 years of age with large tumors should be
scheduled for surgery with expected favorable results (85).
For the elderly patients with HCC, predictors of postoperative survival are not well known. So far, only a few papers
revealed differing findings by multivariate analysis. Hanazaki
et al. (83) reported that liver cirrhosis and vascular invasion
were independent prognostic factors for the survival of postresectional elderly HCC patients. Zhou et al. (97) found that
ChildPugh grading, portal vein tumor thrombus, and

EdmondsonSteiner grading were prognostic factors.


However, other authors failed to yield similar results.
Postoperative recurrence of HCC is the most important factor affecting the survival of patients who underwent radical
resection. Poor results in some series can be explained by a
high proportion of patients with cirrhosis. If the amount of
resected nontumors liver parenchyma is reduced, resection of
the primary liver tumor is justified despite narrow surgical
resection margins. A significant reduction in postoperative
mortality, as well as morbidity can be achieved by this
approach. When postoperative complications occur, they do
not correlate with the amount of liver resected but with preoperative liver function and intraoperative haemorrhage (71).
However, the prognosis following resection for HCC remains
unsatisfactory because of the high incidence of recurrence in
the liver remnant; the cumulative 5-year recurrence rates after
curative hepatectomy are <70% (98). Therefore appropriate
management of recurrent HCC is important to improve longterm outcomes after hepatectomy.
Many studies have supported favorable results after repeat
hepatectomy for recurrent HCC (89). Repeat hepatectomy is
the first choice for patients with preserved liver function (18).
Even for the elderly patients with recurrent HCC, repeated
hepatectomy has been recommended to achieve better survival
if these tumors were resectable (83).
Patients with recurrent HCC are older than those with primary HCC. Repeat hepatectomy for recurrent HCC is safe
even for patients aged more than 75 years, especially when
they underwent limited hepatectomies (89).
Recently, an alternative strategy of primary hepatectomy followed by liver transplantation for recurrent HCC (salvage liver
transplantation) has been proposed (29). Percutaneous ablation therapy may also be a preferable therapeutic modality for
small-sized or small-volume HCC; however, there have been
only a few studies on ablation therapies for recurrent HCC,
and the overall 3-year survival rate after ablation therapy was
43% to 48%, which is less than the survival rates obtained after
repeat hepatectomies (>70%) in certain centers (89). Not only
younger patients but also elderly patients with early-stage
HCC might benefit from this modality, which is less invasive
than hepatectomy. Selection criteria for elderly patients with
recurrent HCC who are good candidates for repeat hepatectomy remain to be determined, and the age limitations for
such an aggressive operative approach are not clear at present.
Nevertheless, advanced age by itself does not have an adverse
effect on operative outcomes, including postoperative complications and long-term prognosis, after repeat hepatectomies
on patients with recurrent HCC. Repeat hepatectomy may
therefore be justified for treating recurrent HCC in selected
elderly patients.
In conclusion, both the short-term and long-term outcome
of resection of HCC seems similar to the younger in carefully
selected elderly patients, even though elderly have a higher incidence of associated diseases. HCC in the elderly is less HBVassociated, less advanced, and less aggressive. Elderly patients
with preoperative alcohol abuse should be followed up very
closely, even after R0 surgery, since alcohol abuse is strongly
correlated with postoperative recurrence and poor survival.

49

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Hepatectomy is safe for the elderly HCC patients without
preoperative comorbidities or with well-controlled preoperative comorbidities.

financial cost
In the current climate of scarce health care resources, treatment for elderly patients has been under close scrutiny. Several
studies have shown that elderly patients have benefited from
liver resection for malignancy with results comparable to those
younger than 70 years of age. The use of health care resources
in terms of intensive care unit and in-hospital stays is no different than in the younger population, and some of this costsaving can be attributed to better support in terms of
anesthesia and community nursing (32). Therefore careful
selection of patients using the ASA grade and meticulous surgical technique are essential to achieve better outcomes after
hepatic resection in patients over the age of 70 years.

conclusions
Age alone should not be considered a contraindication for
liver resection: hepatectomy is safe, effective, and a curative
therapy in the elderly. Major hepatectomies are the feasible
procedure in patients older than 70 years who have preserved
liver function and controllable medical conditions, yielding
close to 0% operative mortality and low morbidity rates in
specialized tertiary centers.

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Small solitary hepatic metastases: when and how?


David L. Bartlett and Yuman Fong

introduction
The management of patients with small hepatic metastases
from colorectal cancer and other histologies requires the consideration of many diverse patient- and tumor-related factors.
These factors include the natural history of the tumor type, the
expected cure rate after surgical treatment, effectiveness of
alternative treatments, and the morbidity of surgical resection.
In general, the indications for any major surgical procedure
include the potential for cure, prolongation of survival, and
palliation of symptoms. For metastatic tumors to the liver in
selected cases, the cure rate may be over 50% for colorectal
cancer (1), but will be exceedingly rare for other histologies
such as gastric cases, and melanoma and sarcoma. Small
metastases to the liver generally do not cause symptoms
(except for hormone secreting neuroendocrine tumors) and,
therefore, palliation of symptoms is not a common indication
for management of these lesions. Nevertheless, many issues
remain unresolved. Does resection of a small solitary hepatic
metastasis prolong survival in cases where the patient is likely
to develop widespread metastases in the future? Is there any
harm in allowing a tumor to go untreated for a period of time,
knowing that with close follow-up the resection option may
still be possible in the future? Do metastases metastasize such
that a delay in management may obviate the curative option?
Unfortunately, all of these difficult issues are only addressed by
sparse data in the literature.
The risk and extent of the surgical procedure plays a significant role in the decision making for management of small
hepatic metastases. It is more reasonable to excise an enlarged
subcutaneous lymph node for metastatic cancer than it is to
perform a hepatic lobectomy when the chance of benefit is
low in both cases. As other less invasive ablative options
become routine therapy, it may be reasonable to consider
these options in cases where surgical resection is unreasonable. These alternative options include percutaneous
approaches at ablation such as radiofrequency ablation and
percutaneous alcohol injection (2). Laparoscopic procedures
may also be an alternative for the management of small
hepatic metastases, including laparoscopic resection of
tumors and laparoscopically directed ablation such as cryotherapy. If the risks, discomfort, and hospital stay are truly
minimal, then it becomes reasonable to consider local treatment of these lesions, even with a small chance of overall
benefit to the patient.
This chapter will provide an overview of the data on survival
benefit after resection of hepatic metastases and the techniques
of surgical management. A brief discussion of minimally invasive and percutaneous procedures for management of small
solitary hepatic metastases will follow. In addition, a discussion of the role for adjuvant therapy after resection or ablation
of the hepatic metastases will be included.

survival results for hepatic


metastasectomy
While the purpose of this chapter is not to provide an in-depth
review of the results of hepatic metastasectomy, a general sense
of expected cure rate and prolongation of survival after hepatic
metastasectomy for various histologies is required in order to
make an informed decision regarding resection of small
hepatic metastases.
Colorectal Metastases
Colorectal cancer, compared to other histologies, is more likely
to present as disease isolated to the liver. The natural history of
unresected solitary hepatic metastases from colorectal cancer
was described by Wagner et al. where 39 patients with solitary
metastases did not undergo therapy and the median survival
was 24 months (3). Wood et al. described 15 patients with solitary hepatic metastases left untreated with a mean survival of
17 months (4).
There is a considerable body of literature on the results of
hepatic metastasectomy for colorectal cancer. The overall
5-year survival ranges from 22% to 39% (5). In many studies,
low number and small size are associated with improved prognosis such that a small solitary metastasis from colorectal cancer has a greater than 50% of 5-year survival. Nuzzo et al.
report 56% actuarial 5-year survival in patients with solitary
metachronous hepatic metastases from colorectal cancer less
than 4 cm in size (1). Table 6.1 reviews the results of the largest
series for solitary metastasectomy. After resection of solitary
metastases from colorectal cancer, 5-year survival ranges from
30% to 47% (610). These reports do not consider the small
solitary metastases separately from the entire group of solitary
metastases. The size of the lesion is expected to affect prognosis and, therefore, the actual results for small solitary hepatic
metastases may be even better than the numbers reported in
Table 6.1. Liver resection for hepatic colorectal metastases is,
therefore, safe and effective, and may be curative.
Neuroendocrine Metastases
For cancers of other than colorectal origin, patients with
hepatic metastases from neuroendocrine tumors have been
thought to be the most likely to benefit from surgical resection.
Certainly, if the tumor were symptomatic for either hormonal
or physical reasons, resection should be considered even though
cure is unlikely. Because of the indolent nature of these tumors,
durable palliation can be achieved with cytoreduction. Fiveyear survival rates for untreated hepatic metastases from neuroendocrine tumors have ranged from 13% to 54% (1115).
In patients with no symptoms, the case for surgical resection, or any treatment for that matter, is less clear. We and
others (16) have adopted a very aggressive approach even
for asymptomatic tumors based only on retrospective data.

53

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Chen et al. compared liver resection for neuroendocrine tumors
with a retrospectively matched cohort who did not undergo
resection, demonstrating improved survival after resection (17).
The general recommendation is for aggressive surgical management of neuroendocrine metastasis (18). We acknowledge
that the variable growth rate and sometimes indolent nature of
these tumors make firm conclusions based on retrospective
data without a nontreated control group suspect. The rarity of
these tumors, however, does not allow for random assignment
trials. Certainly for small hepatic metastases, aggressive surgical
resection is indicated, while it is acknowledged that definitive
proof of its benefit may never be achieved.
Noncolorectal, Nonneuroendocrine Metastases
For histologies other than colorectal or neuroendocrine cancer, the utility of hepatic metastasectomy is not as obvious. For
these tumors, the liver is rarely the sole site of disease; liver
metastases are rarely the ultimate cause of death, nor does it
contribute significantly to symptoms prior to death. Nevertheless, selected cases of disease isolated to the liver after a long
disease-free interval raise the possibility of a single site of metastatic disease that could be cured with surgical therapy.

Table 6.1 Survival After Hepatic Resection for a Solitary


Colorectal Metastasis

Author

Date

Actuarial
5-year
survival
(%)

Hughes et al. (6)


Rosen et al. (7)
Scheele et al. (8)
Taylor et al. (9)
Fong et al. (10)

1988
1992
1995
1997
1997

509
185
180
A077
240

37
30
36a
47
47

Median
survival
(months)

45
54

Actual 5-year survival.

Table 6.2 reviews the largest series for hepatic metastasectomy


with a variety of histologies.
Breast cancer
Many reviews have been published on hepatic metastasectomy for breast cancer. Due to the high incidence of breast
cancer and the frequency of liver metastases for this histology, the first site of metastases is frequently observed to be
hepatic. In highly selected patients, favorable results of section of such liver metastases have been reported. Raab et al.
reported a 5-year survival of 18.4% in 34 patients after
hepatic metastasectomy for breast cancer (19). Elias et al.
reported 9% 5-year survival after resection in 21 patients
(20). The relatively few patients in these reports compared
to the total number of breast cancer patients in each institution during the study period reflect the degree of patient
selection for surgery. The survival rates reported are actuarial survival rates and the actual cure rate is much lower. At
most, hepatic metastasectomy for breast cancer should be
considered cytoreductive. It may delay the development of
symptoms and prolong survival, but it has very little chance
of curing the disease.
Sarcoma
Similarly, hepatic resection for sarcoma metastases may be
associated with long-term survival in highly selected patients,
but it is unlikely to result in cure. In a series of 14 hepatic
resections for metastatic sarcoma, recurrence was found in all
patients during follow-up, and 11 of 14 failed in the liver (21).
The median survival in that series was 30 months.
Melanoma
Metastatic cutaneous melanoma to the liver has been resected
with long-term survival, but these tumors also ultimately
recur (22). The erratic behavior of melanoma makes conclusions regarding the benefit of hepatic metastasectomy difficult.

Table 6.2 Survival Following Hepatic Metastasectomy for Noncolorectal Histologies


Author
Chen et al. (17)
Que et al. (57)
Harrison et al. (26)
Jaques et al. (21)
Harrison et al.26
Elias et al. (20)
Raab et al.19
Ochiai et al. (24)
Bines et al. (25)
Harrison et al. (26)
a

Histology
Neuroendocrine
Neuroendocrine
Genitourinaryb
Sarcoma
Breast/melanoma/sarcoma
Breast
Breast
Gastric
Gastric
Gastrointestinale

4-year survival.
Includes renal (5), testicular (9), adrenal (7), ovary (7), uterine (4), cervix (2).
4 of 21 actual 5-year survivors.
d
1 of 7 actual 5-year survivors.
e
Includes gastric (5), pancreatic (2).
NR: not reached.
b
c

54

N
15
74
34
14
41
21
34
21
A07
A07

Actuarial 5-year
survival (%)

Median survival
(months)

73
73a
60
A00
26
A09
18
19c
14d
A00

NR
NR
NR
30
32
26
27
18
15
25

SMALL SOLITARY HEPATIC METASTASES: WHEN AND HOW?


Only in highly selected cases is it appropriate to consider resection of cutaneous melanoma. Ocular melanoma, on the other
hand, has a unique natural history. Ocular melanoma preferentially metastasizes to the liver and the majority of patients die of
liver failure as a direct result of tumor progression. Anecdotal
reports exist of long-term survival after metastasectomy for
ocular melanoma (23), although these tumors are also almost
always multifocal and resection of what appears to be a solitary
metastasis is most often associated with liver recurrence. These
hepatic metastases may show up many years after the treatment
of the primary tumor. A long disease-free interval reflects a slow
tumor doubling time, and suggests resection may achieve durable palliation. Usually in this disease, however, the appearance of
a solitary liver metastasis is merely a precursor of the later
appearance of multiple metastases.
Other gastrointestinal cancers
In general, hepatic metastasectomy for gastrointestinal
primaries other than colorectal is not associated with prolonged survival. For tumors such as esophageal, gastric,
small bowel, and pancreatic cancer, the pattern of spread
includes regional lymph nodes, the peritoneal cavity, and
lung metastases in addition to liver metastases. It is unlikely
that these patients will die of liver failure as a result of progression of hepatic metastases, but instead, suffer other gastrointestinal sequelae from extrahepatic tumor progression.
A major operative procedure can be of significant detriment to these patients with aggressive cancers where survival is expected to be of the order of weeks to months.
Nevertheless, even for these tumors, selected cases exist
where one might consider resection, and the literature contains anecdotal reports of long-term survivors after liver
resection (24,25).
Genitourinary tumors
For noncolorectal, nonneuroendocrine tumors, metastases
from genitourinary primaries seem to have the best prognosis
following hepatic metastasectomy. In a recent review by
Harrison et al., 34 patients underwent hepatic resections for
genitourinary primaries (including testicular, adrenal, ovary,
renal, uterine, and cervix) with a 5-year actuarial survival of
60% (26). Other investigators have reported prolonged survival after resection for renal cell cancer (27) and adrenal cancer (28). While the natural history of genitourinary tumors
contributes to these remarkable results, it does suggest a survival benefit to resection in selective cases.

do metastases metastasize?
For small solitary hepatic metastases, where many months
of growth would still not preclude resection, the question is
whether a waiting period would allow for further spread of
the tumor from the metastatic deposit itself. If metastatic
tumors were unable to further metastasize, waiting for the
first sign of progression prior to initiating treatment and
allowing other metastatic disease to declare itself would
seem a reasonable approach. If, however, metastases are able
to spread during that waiting period, then the chance of
potential cure may be adversely affected by the delay in

definitive treatment. Unfortunately, it is clear that metastatic tumors do have the potential to metastasize themselves, and this must be considered when recommending
observation alone.
Experimental evidence suggests that cells from spontaneous
metastases are more likely to metastasize than cells populating
the parent neoplasm (29). Clinically, the most obvious examples of metastases from metastatic colorectal cancer deposits
are in the cases of perihepatic lymph node metastases (30) and
satellite-tumor formation (31).
Published data would indicate that metastases to periportal
lymph nodes occur in 10% to 20% of cases of hepatic colorectal
metastases (30). The presence of lymph node metastases portends a poor prognosis. Therefore, excision of liver tumors before
they spread to regional lymph nodes would be advantageous.
A recent paper examined the incidence of satellite micrometastasis in colorectal liver metastases by careful histologic
examination of resection specimens and found that 56% of
specimens had micrometastases as far as 3.8 cm away from
the tumor being resected (31). In some cases, these satellites
could be traced to the original metastasis by a trail of cells,
suggesting spread from the original metastasis. As discussed
previously, the presence of satellitosis is an important independent poor prognostic factor. It may be that a delay in
resection allows for the development of satellitosis, which
negatively impacts on prognosis. On the other hand, the
presence of satellitosis may be an indicator of biologic aggressiveness, which portends a poor prognosis regardless of when
the tumor is resected.

patient selection
Colorectal Metastases
In order to decide when surgical resection is reasonable for
small solitary hepatic metastases, it is important to review
prognostic factors that are independent of size and number,
which may influence the decision regarding management of
these tumors. Many studies have examined data on prognostic
factors for outcome after hepatic resection for colorectal
metastases. The time to development of liver tumor after
resection of the primary, pathologic margin, stage of the primary tumor, tumor number, carcinoembryonic antigen levels,
satellitosis, extrahepatic disease, and positive surgical margin
have all been shown to predict survival after hepatic resection
for colorectal metastases independent of size (7,8,10,32).
Extrahepatic disease is considered a contraindication to
hepatic resection. Even the presence of perihepatic lymph
nodes portends a poor prognosis and generally is felt to be a
contraindication to resection. Particularly in the cases of small
solitary hepatic metastases with extrahepatic disease, there
would be no advantage to resection or ablation of the liver
tumor because systemic disease will likely be the ultimate
cause of death regardless of what is done with the liver
metastases. Of the other various factors that are prognostic for
outcome, surgical margin, and satellitosis are the least useful in
patient selection. No one would subject a patient to surgical
resection expecting a positive margin. Satellitosis cannot be
easily assessed preoperatively and therefore is a poor selection
criterion for surgery.

55

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


We analyzed our recent data on factors prognostic for outcome after resection of hepatic metastases from colorectal
cancer (33). In data derived from our last 1001 liver resections
for this disease, the seven factors found to be independent
predictors of poor long-term outcome were
1. node positive outcome,
2. presentation of liver disease within 12 months of the
primary cancer,
3. CEA > 200 ng/dl,
4. number of liver tumors > 1,
5. size > 5 cm,
6. positive margin, and
7. extrahepatic disease.
From this, we formulated a clinical risk score (CRS) based on
the first five of these factors for use in patient selection for surgery and for stratification of patients for clinical studies. Using
one point for each criterion, a summed score of 02 puts patients
in a low-risk group and is a strong indication for hepatectomy.
In the patients with small tumors, a maximum score of 4 is possible. The 5-year survival of patients with small tumors and 02
points on the CRS is 47% and the median survival is 56 months
(33). Patients with a score of 34 are in a high-risk group, with a
median survival of 32 months and 5-year survival of 24% (Fig.
6.1). In these high-risk patients, a period of observation with no
therapy or systemic chemotherapy allowing for the extent of
metastases to declare themselves is reasonable. Improved imaging techniques such as fluorodeoxyglucose positron emission
tomography (FDG PET) scanning should be considered and
may help discover extrahepatic disease noninvasively in these
patients at high risk for additional cancer (34). Finally, these
patients should be considered for clinical studies of aggressive
adjuvant chemotherapy after liver resection.
1.0

Survival

0.8

0.6

0.4

0.2

0.0
0

12

24

36

48

60

Months
Figure 6.1 Prediction of long-term outcome for small (<3 cm) (N = 293)
metastatic deposits based on clinical risk score (CRS). CRS is based on the
following five criteria: (1) node positive primary cancer, (2) disease-free interval <12 months, (3) number of liver tumors >1, (4) size of liver tumor >5 cm
and (5) CEA > 200 ng/dl. For score = 02 (N = 236) (open box), the median
survival was 56 months and the 5-year survival 47%. For score = 34 (N = 57)
(filled triangles), the median survival was 32 months and the 5-year
survival 24%.

56

Neuroendocrine Tumors
Patients with symptomatic neuroendocrine tumors should be
considered for resection or ablation. For the small tumor,
symptoms are most likely derived from hormonal secretion by
the tumors, and such hormone levels will also provide a
marker for effectiveness of the ablation or resection. For
asymptomatic tumors, a period of observation to allow assessment of the pace and aggressiveness of the tumors is reasonable when the tumors are small. At the first signs of progression,
resection or ablation should be considered.
Noncolorectal, Nonneuroendocrine Tumors
Harrison et al. defined prognostic factors involved in the resection of noncolorectal, nonneuroendocrine hepatic metastases
(26). In this study, 96 patients underwent liver resection. The
prognostic factors of significance on multivariate analysis
included the disease-free interval (>36 months), curative
resection (versus palliative incomplete resection), and primary
tumor type. Their conclusions would suggest that regardless of
histology, with a long disease-free interval patients may benefit
from surgical resection.

resection techniques
For small solitary metastases to the liver, the goal of resection
is to completely excise the tumor while preserving the maximum normal hepatic parenchyma. Preserving parenchyma
facilitates postoperative recovery and also provides flexibility
for further resections should intrahepatic recurrences
occur (35). Small surface-oriented metastases can be excised
using a nonanatomic wedge resection, whereas deeper lesions
require formal segmentectomies or sectorectomies. A goal of
at least a 1 cm margin is reasonable (36). The use of intraoperative ultrasound is important to rule out other small hepatic
metastases, which may not be evident on preoperative scans
and in defining the intersegmental planes for designing the
approach to segmentectomy. Even for wedge resections, ultrasound is beneficial in defining the vascular anatomy around
the lesion, which may help minimize blood loss.
Wedge Resections
Wedge resections must be performed meticulously to avoid
inadvertently leaving a positive margin. Large chromic liver
sutures can be placed and used for retraction during dissection. The parenchymal dissection should be performed
along the lines used for other forms of liver resection. We
prefer the Kelly clamp technique where the clamp is used to
crush the normal parenchyma, exposing vessels that are then
clipped, tied, suture ligated, or stapled using a vascular stapling device (37). The Pringle maneuver is used intermittently for 5 minutes at a time followed by reperfusion of the
parenchyma, during which time the argon beam coagulator
is used to coagulate small bleeding vessels on the surface.
This technique is superior to the simple use of electrocautery for the dissection, which is often attempted for what
seems to be routine wedge resections. The char effect of the
electrocautery prevents adequate visualization of the anatomy, making it quite easy to stray into large vessels or into
the tumor.

SMALL SOLITARY HEPATIC METASTASES: WHEN AND HOW?


The most difficult margin in performing a wedge resection
is the deep margin of dissection. Using intraoperative ultrasound, the depth of dissection should be measured prior to the
initiation of parenchymal dissection, including at least a 1-cm
margin deep to the tumor. The dissection should be carried
down perpendicular to the liver surface to the predetermined
depth. At this point, the tumor can be lifted up and dissection
can proceed horizontally across the base of the wedge. The
tendency to resect with a V-shaped approach is more likely
to be complicated by a positive deep margin. At the end of the
dissection, the Pringle maneuver is removed and the argon
beam coagulator is used to control bleeding vessels. Careful
examination is made for any evidence of a bile leak, which is
controlled with suture ligature.
For larger lesions where it is especially difficult to achieve
the deep margin safely, a cryoassisted wedge resection can be
performed (38). The cryotherapy probe is inserted into the
tumor and freezing is begun with real time ultrasound imaging. When the zone of freezing is confirmed by ultrasound to
be at least 1 cm beyond the tumor, wedge resection is performed using the freeze margin as the margin of resection.
The cryotherapy probe makes a ready retracting device and
the parenchyma is usually easy to dissect at the margin of the
ice-ball. Freezing must continue intermittently during dissection to ensure that the ice-ball does not retract and expose
the tumor.

clamped at its junction with the vena cava during parenchymal


transection to further minimize blood loss.
When the solitary metastases lie near an intersegmental
plane, two segments can be removed. This is most easily done
as a formal sector such as the left lateral sectorectomy (segments II and III) and right posterior sectorectomy (segments
VI and VII). The caudate lobe (segment I) can be resected as
an isolated segmentectomy when the tumor is confined to this
lobe (42). This requires a more extensive dissection, including
complete division of all the perforating caudate veins draining
directly into the vena cava as well as the numerous small portal
triads extending off the main left pedicle at the base of the
umbilical fissure.
Figure 6.2 demonstrates a case of a small, solitary segment of
hepatic metastasis for colorectal cancer, which was detected on
an MRI scan used for screening because of a rising CEA.
Although this was a surface lesion, intraoperative ultrasound
revealed the segment VI triad immediately adjacent to the
tumor. The segment VI triad was located by ultrasound and
ligated at its origin with minimal parenchymal dissection. The
intersegmental planes were then marked by electrocautery and
a formal segmentectomy was performed with negative margins. While an aggressive resection was indicated and performed, the patient can still undergo a formal left or right
hepatic lobectomy in the future if indicated. No dissection of
the vena cava or porta hepatis was required.

Segmental Resections
For all but the most superficial lesions, we prefer a segmental
approach for the resection of tumor (39). Segmental resections have a significantly lower rate of pathologic positive
margins, and this translates into improved long-term
survival (40). Small, deep solitary metastases and surface
lesions adjacent to major vascular structures lend themselves
particularly well to segmentectomies or sectorectomies. The
intersegmental planes can be identified intraoperatively using
vascular landmarks with the aid of intraoperative ultrasound.
Using these planes for parenchymal dissection will minimize
blood loss and help ensure a safe margin.
Inflow occlusion for the segment can almost always be performed first, thereby producing demarcation of the segmental
planes to further enhance the dissection. The portal triad to
segments II, III, and IV can be identified and controlled within
the umbilical fissure with little parenchymal dissection (37).
The right posterior sectoral pedicle can be found by dividing
the parenchyma along a horizontal cleft (fissure of Gans) present on the inferior surface of the right lobe of the liver. The
pedicle can be traced to its bifurcation to segments VI and VII
for control of the individual segmental portal triads. The anterior sectoral pedicle can be dissected from an inferior or anterior approach.
The major hepatic veins lie within the intersegmental planes
and can be a source of significant blood loss during the
parenchymal transection phase of a segmentectomy. The use
of low central venous pressure (05 mmHg) during parenchymal dissection can decrease back bleeding in these veins (41).
Extrahepatic control of the left, middle, and right hepatic veins
can also be achieved and the vein of concern temporarily

Morbidity and Mortality


The mortality rates for major hepatic resection have decreased
significantly over time to a common reporting of mortality in
the 1% to 4% range (43). These values are even lower for
wedge resections and segmentectomies. In a recent report of
270 wedge or segmental resections, the operative mortality
was 0.5% (40). This low mortality is not surprising considering that the main cause of death in studies of liver resection is
liver failure secondary to inadequate residual normal parenchyma, an unlikely event for resection of small solitary hepatic
metastases where minimal normal parenchyma is sacrificed.
While mortality rates are low, the complication rate for major
hepatic resection is still relatively high, ranging from 20% to
50% (5). Bile leaks, perihepatic abscess, hemorrhage, cardiopulmonary complications, pleural effusions, pneumonia, and
pulmonary embolism are among the most common complications (43). Many of these could be expected after segmentectomy and wedge resections as well as major hepatic resections.
Even though these complications do not translate into a high
mortality rate, they may affect recovery time and quality of life.
While this is not a significant issue for patients expected to
undergo a long-term disease-free interval or cure, it may be significant for patients whose survival is expected to be of the
order of months. For those patients with aggressive tumors
who are likely to fail outside the liver in the near future, less
invasive techniques which are associated with a lower complication rate and quicker recovery time are more appealing.
Ablative Techniques
Other minimally invasive techniques include local ablative
therapies such as laparoscopically directed cryotherapy (44) or

57

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

(C)

(D)

Figure 6.2 An example of a small, solitary colorectal metastasis to segment VI. (A) MRI reveals subtle abnormality not seen on CT scan. (B) Intraoperative ultrasound reveals the tumor and adjacent segment VI portal vein. (C) Intersegmental planes have been marked on the liver capsule with electrocautery and parenchymal dissection begun. (D) Resected segment with tumor (microscopic negative margins). (Special thanks to Dr Peter Choyke for MRI scan.)

radiofrequency ablation (45). These techniques will be discussed further in chapter 8. They provide ideal alternatives to
laparotomy and major liver resection for the treatment of
small solitary hepatic metastases, since the small tumor is
the most likely to be completely treated by ablation techniques. Furthermore, treatment by ablative techniques does
not preclude future resection.
Percutaneous approaches to tumor ablation are even more
attractive than laparoscopic procedures. Local injection of
toxic agents such as ethanol has been shown to be effective
for hepatocellular cancers, however these agents have not
been proven for other histologies and are known to be
poorly effective for colorectal cancer (2). Radiofrequency
ablation can be performed percutaneously under ultrasound
guidance with local anesthesia. Figure 6.3 demonstrates a
case of a metastatic pancreatic cancer 2 years after a dramatic primary response to gemcitabine and radiation therapy. Because the patient will likely begin to fail in multiple
sites in the near future with limited survival potential, a laparotomy and hepatic resection was not considered reasonable. She was treated with percutaneous radiofrequency
ablation, achieving a good zone of necrosis encompassing
the mass, and she spent only one day in the hospital with
very minimal discomfort. How such procedures, which have
low morbidity and which maintain quality of life, will factor

58

in the treatment of patients with small hepatic metastases


must be addressed by studies with sufficient follow-up to
define the local recurrence rate.

adjuvant chemotherapy
The role for adjuvant systemic chemotherapy after the
removal of small solitary hepatic metastases is not well
defined. Even for hepatic colorectal metastases, which are
commonly treated with surgery, data on adjuvant chemotherapy after liver resection is sparse. Two retrospective studies
have suggested a benefit of adjuvant systemic chemotherapy
after metastasectomy, but others have not supported this
(6,4648). Use of systemic chemotherapy after resection of
hepatic colorectal metastases is based mainly on data demonstrating adjuvant 5-fluorouracil (5-FU) and levamisol or
5-FU and leucovorin to decrease recurrence rate and improve
survival when used after resection of the primary tumor (49).
It is hoped that a similar benefit will be seen when 5-FUbased chemotherapy is used after metastasectomy. Current
practice is to offer adjuvant 5-FU-based chemotherapy after
hepatic resection to patients who have had no previous chemotherapy. There are currently no data to support the use of
irinotecan and oxaliplatin in an adjuvant setting, although
studies are in progress.

SMALL SOLITARY HEPATIC METASTASES: WHEN AND HOW?

(A)

(B)

(C)
Figure 6.3 An example of a small, solitary pancreatic cancer metastasis treated with percutaneous radiofrequency ablation. (A) Pretreatment CT scan reveals
hypodense 3 cm right lobe liver metastasis. (B) Ultrasound hoto with radiofrequency probe inserted into tumor. (C) Post-treatment scan (3 weeks) reveals large
zone of necrosis replacing prior tumor. (Special thanks to Dr Thomas Shawker for ultrasound photo.)

For patients with hepatic colorectal metastases, the most


common site of tumor recurrence after liver resection is the
remnant liver (50). In the treatment of patients with small
hepatic metastases, there is particular concern that even
smaller undetected metastases may subsequently present as
a liver tumor recurrence. Regional chemotherapy to treat
the liver site is therefore a theoretically attractive option for
adjuvant care. Data addressing the utility for such hepatic
arterial infusional (HAI) chemotherapy had been sparse,
consisting only of four small single-arm studies (5153) and
a single, small, randomized trial consisting of 36 patients
(54). These preliminary studies demonstrated safety of such
an approach, but efficacy data were insufficient to support
the routine use of adjuvant intraarterial chemotherapy. Two
large randomized trials examining adjuvant HAI have been
completed. In the first trial (55), 224 patients from 25 centers
were randomized to either no adjuvant therapy or adjuvant
HAI 5-FU + systemic folinic acid. Although no difference
was found between the groups, technical factors compromised this study such that only 34 of the 114 patients
randomized to chemotherapy completed the adjuvant
treatments. In another study, Kemeny et al. randomized
156 patients to either systemic 5-FU + leucovorin or HAI
floxuridine (FUDR) + systemic 5-FU after complete resection of tumor (56). There was a significant survival advantage to HAI that is most likely related to local liver tumor
control. We believe HAI chemotherapy is effective and

should be considered as an adjuvant to resection of hepatic


colorectal metastases.
For noncolorectal, nonneuroendocrine histologies metastatic to the liver, the most likely cause of death will be related
to the disease outside the liver, regardless of how the liver is
managed. For patients who are likely to develop systemic
metastases in the near future, it may be reasonable to offer
chemotherapy prior to resection. If the tumor responds, then
a resection will be performed with confidence that other
micrometastatic disease may be effectively treated with chemotherapy. If the tumor does not respond and the liver
remains the only site of metastatic disease, resection is performed with increased confidence conferred by the longer
period of observation. If the patient advances systemically
during chemotherapy, then it is very unlikely that a resection
would have been of benefit and the patient will have avoided
the potential morbidity, pain, discomfort, and recovery time
of an hepatic resection. That patient can go on to obtain
second-line chemotherapy, investigational chemotherapy, or
have no additional treatment.

conclusions
Algorithms for the management of small solitary hepatic
metastases are shown in Figure 6.4. Both patient and tumor
characteristics must be considered in making management
decisions. The most important tumor-related characteristic is

59

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Colorectal
metastases

High CRS
(34)

Low CRS
(02)

Observation
or
chemotherapy

Resection

No
extrahepatic
progression

Extrahepatic
progression

Resection
or ablation

Chemotherapy

Ablation

Resection

Adjuvant
therapy
protocol

Adjuvant
therapy
protocol

(A)
Neuroendocrine
metastases

Symptomatic

Non-colorectal
non-neuroendocrine
Asymptomatic
Long disease-free
interval

Resection

Ablation

Short disease-free
interval

Observation
Resection
Progression

No
progression

Resection
or ablation

Observation

(B)

Effective
chemotherapy
(>20% response)

No effective
chemotherapy

Trial of
chemotherapy

Ablation vs
observation

(C)

Figure 6.4 Algorithms for the management of small hepatic metastases. (A) Algorithm for colorectal metastases (CRS, clinical risk score). (B) Algorithm for
neuroendocrine metastases. (C) Algorithm for non-colorectal, non-neuroendocrine metastases.

histology. For patients with colorectal cancer (Fig. 6.4A), the


prognostic factors for tumor recurrence after resection are well
defined. Using the clinical risk score (CRS) as selection criterion, patients with CRS = 02 are ideal candidates for resection. Those with CRS = 34 should consider observation or
chemotherapy prior to a definitive hepatic procedure. Immediate ablation or resection should be performed in the setting
of a clinical trial, and most appropriately a trial examining
adjuvant therapy.
For neuroendocrine cancers (Fig. 6.4B), symptomatic
tumors should be treated with resection and/or ablation when
possible. When the cancer is found in an asymptomatic patient,
a period of observation is not unreasonable because of the
often indolent nature of these tumors. At resection, the principle should be to leave as much normal liver behind in order
to minimize the risk of liver failure and in order to allow for

60

repeat anatomic liver resections in the future for recurrent disease. Enucleation with positive margins is acceptable for treatment of this histology because resection is almost never
curative, and such cytoreduction can provide significant and
durable palliation with minimum risk.
For patients with small, solitary, noncolorectal nonneuroendocrine tumors, the most significant factor in terms of
prognosis seems to be the disease-free interval (Fig. 6.4C).
For patients with a long disease-free interval from primary
resection a curative surgical resection is indicated as the
most effective means of therapy. While it may be still unlikely
that these patients can be cured, they must be given the benefit of the doubt and the most optimal procedure performed.
The definition of long has been arbitrarily set at 36 months
by Harrison et al. (26), but in reality it must vary according
to histology. For gastric cancer, 1224 months would be

SMALL SOLITARY HEPATIC METASTASES: WHEN AND HOW?


considered long, whereas for ocular melanoma, 35 years
would be more reasonable.
Patients with a short disease-free interval from a tumor
with a poor prognosis should undergo a trial of chemotherapy if there is a known effective agent. If no effective agent
exists (as is the case for most solid malignancies), then these
patients are ideal for an experimental, minimally invasive,
local ablative therapy. This provides an advantage to observation alone, given the low but definite risk of the metastases
spreading during the observation period. It will be psychologically more comforting to the patient to know that the
lesion has been ablated, and risk, pain, and recovery duration
are minimal. Observation alone is also quite reasonable, but it
is often not accepted by patients. Patient-related factors must
also be taken into consideration. Patients who have concomitant illnesses that make them poor operative candidates may
be better served with a minimally invasive or percutaneous
technique, even in the case of potentially curable metastases
from colorectal cancer.
Because of improvements in diagnostic techniques and the
routine use of serum tumor markers, the detection of small
solitary hepatic metastases from various tumors will likely
increase in the future. A uniform approach to these patients
such as that which is outlined in the treatment algorithm
should be considered.

key points
Factors that determine management

Natural history of tumor type


Expected cure rate after surgical treatment
Effectiveness of alternative treatment strategies
Morbidity of surgical resection

Survival rates following hepatic resection

Good evidence for long-term survival


Colorectal metastases
Neuroendocrine metastases
Survival possible in highly selected cases
Breast cancer
Sarcoma (especially gastrointestinal stromal
tumors)
Melanoma

Patient selection factors in colorectal metastases

Contraindications
Extrahepatic disease (except solitary pulmonary
metastases)
Positive hilar lymph nodes
Relative contraindications
Presentation within 12 months of resection of
primary tumor
CEA >200 ng/dl
>1 liver tumor
Tumor >5 cm in size
Positive resection margin

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Managing complications of hepatectomy


Fenella K. S.Welsh, Timothy G. John, and Myrddin Rees

introduction
The safety of elective liver surgery has improved dramatically
in the past 30 years. A multicenter American series comprising
621 liver resections published in the late 1970s reported a 13%
mortality (1). By contrast, recent large published series
describe posthepatectomy mortality rates of 0% to 4.4%, with
19.6% to 45% morbidity (28) (Table 7.1). Furthermore, individual units have demonstrated a significant reduction in
morbidity and mortality over time, despite ever-widening the
indications for hepatectomy (6,8). This dramatic improvement in immediate postoperative outcome can be explained
by increased specialization of liver surgery in high-volume
centers (9), better selection of patients in terms of hepatic
functional reserve and comorbid conditions, advances in surgical technique, including greater understanding of hepatic
segmental anatomy and improved instrumentation for the
parenchymal transection. Furthermore, anesthesia and critical
care has improved enormously, the routine use of low central
venous pressure (CVP) anesthesia being a particular advance.
However, even a 20% complication rate remains significant,
particularly if the indication for hepatectomy is for livingdonor transplantation. Furthermore, postoperative morbidity
can also adversely affect disease-specific and disease-free survival (1012). Thus the short- and long-term consequences of
postoperative morbidity, coupled with increasing litigation,
and limited health care resources, has renewed the drive to further improve the immediate outcome from liver resection,
with emphasis on prevention of and improved management of
complications, when they occur. The precise definitions of the
specific complications such as bleeding, bile leak, and hepatic
insufficiency are still without consensus. Moreover, the stratification of the severity of each complication is still unclear.
Standardized definitions, grading, and reporting of the complications of hepatectomy are needed to allow an objective,
quality assessment of outcome data from different units and
further improve results. The system proposed and validated by
Clavien, focusing on the therapeutic consequences of complications in order to rank their severity, is currently the best
available (13). However, it is still not universally adopted
within the surgical community.
A number of studies have attempted to identify the risk factors associated with complications and death from hepatectomy, three of which are detailed in Table 7.2. From these
studies, there is consensus that the estimated blood loss or
blood transfusion rate, the extent of hepatic resection, and an
additional extrahepatic procedure are all independent predictors of morbidity and mortality. In addition, medical comorbidity, an elevated preoperative creatinine, preoperative
thrombocytopenia, or hypoalbuminemia also appear to
increase the operative risk. However, in the Hong Kong
study (8), while cirrhosis per se was associated with increased

postoperative morbidity and mortality on an initial univariate


analysis, it failed to independently predict outcome on subsequent multivariate analysis. Similarly, Belghitis group found
that the in-hospital mortality rate was significantly higher in
those patients with cirrhosis (8.7%) compared to those without underlying liver disease (1%, p < 0.001), but this was not
subjected to multivariate analysis (7). Thus while liver resection in cirrhotic patients is technically more challenging than
resecting normal liver, with a higher incidence of bleeding,
septic complications, and postoperative liver failure (14), these
two studies would suggest that in experienced high-volume
centers, liver resection can be safely performed in patients with
early cirrhosis.
The common complications of hepatectomy may be classified as specific to the procedure or of a more general nature
(Table 7.3). This chapter will deal with these complications in
turn, focusing on their definition, incidence, predisposing factors, prevention, presentation, investigation, and treatment.

bleeding
Incidence
Bleeding is the most feared complication of hepatectomy, both
on the operating table and in the immediate aftermath of surgery. In the 1960s and 1970s, it was the cause of major morbidity and mortality. The 1974 Liver Tumor Survey was a
multicenter series of 621 hepatic resections performed in 98
U.S. centers, published in 1977. It reported a 13% mortality,
with 15 of the 82 deaths (18%) due to exsanguinating hemorrhage in the operating room and bleeding being the documented primary cause of death in 26 of the 76 patients (34%),
where the cause of death could be determined (1). However,
bleeding is now relatively rare, with the median estimated
blood loss for an elective hepatectomy being 345 to 600 ml
(3,6) and the need for perioperative blood transfusion now
being the exception rather than the rule. Indeed, the incidence
of major hemorrhagic complications is rare, 0.7% (7/1005) in
our own series (3). Of these seven cases, there were no on-table
deaths, five patients were treated nonoperatively and two
underwent reexploration for bleeding from a hepaticojejunal
anastomosis and a left caudate branch of the portal vein
respectively. In the Sloan-Kettering series of 1803 patients, the
incidence is similar (1%) (6).
Prevention
Prevention remains the key to the management of bleeding. In
the preoperative assessment, a careful drug history should be
taken. If the patient is on drugs such as aspirin, clopidogrel, or
warfarin, the indication for the treatment should be reviewed,
and the drugs stopped where possible. Patients on warfarin as
prophylaxis for thromboembolic events can be managed with
an inferior vena cava (IVC) filter, placed preoperatively. It is

63

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Table 7.1 Morbidity and Mortality from Hepatic Resection in Recent Large Case-Series
Reference

Years of study

No of centers

No of resections

Imamura
et al.
Rees et al.
Wei et al.
Malik et al.
Jarnagin et al.

19942002

1056

19872005
19922002
19932006
19912001

1
2
1
1

1005
423
687
1803

Belghiti et al.

19901997

747

Poon et al.

19892003

1222

Case-mix
50% HCC
29% cirrhotic
100% CRLM
100% CRLM
100% CRLM
62% CRLM
10% HCC
Elective & emergency.
35% benign 28% HCC
17% CRLM
32% cirrhotic
60% HCC
33% cirrhotic

Mortality

Morbidity

0%

39%

1.5%
1.7%
3.0%
3.1%

25.9%
19.6%
29.5%
45.0%

4.4% all
3.9% elective
8.7% cirrhotic
25.0% emergency
4.9%

22.0%

32.4%

Abbreviations: CRLM, colorectal liver metastases; HCC, hepatocellular carcinoma.

Table 7.2 Three Studies Reporting the Independent Predictors of Morbidity and Mortality after Hepatic Resection
Reference
Jarnagin et al.

Years of study
19912001

No of resections
1803

Belghiti et al.

19901997

478 elective resections,


no cirrhotics

Poon et al.

19892003

1222

Predictors of morbidity
Estimated blood loss
Extent of resection
+ EH procedure
preoperative creatinine
Hypoalbuminemia
Medical comorbidity
Male gender
ASA score
Extent of resection
Steatosis
Blood transfusion
+ EH procedure
Thrombocytopenia
Blood transfusion
+ EH procedure

Predictors of mortality
Estimated blood loss
Extent of resection
+ EH procedure
preoperative bilirubin
Thrombocyt openia
Age
+ EH procedure (in patients with
malignancy)

Hypoalbuminemia
Thrombocytopenia
preoperative creatinine
Major resection
Blood transfusion

Abbreviation:+EH Procedure, additional extra-hepatic procedure.

important to identify patients with tricuspid regurgitation or


right heart disease, where the anesthetist may encounter difficulties in lowering the CVP, as this may influence the extent of
resection. Careful evaluation and correction of coagulation
abnormalities should be performed pre- and perioperatively,
particularly in the cirrhotic patient.
Two key maneuvers are used to prevent bleeding during
hepatic transection: portal triad clamping and low CVP
anesthesia. Portal triad clamping, first described by Pringle
in 1908, reduces hepatic arterial and portal venous bleeding
(15,16). Although a European survey demonstrated that the
use of inflow occlusion is not universal, it did confirm that
most hepatic surgeons resort to it in difficult cases and that
experienced surgeons are more likely to use it routinely (17).
However, a recent systematic review and meta-analysis of the
effect of inflow occlusion on postoperative morbidity and
mortality failed to demonstrate any significant outcome

64

benefit (18). This is confirmed by another systematic review


published in 2009, which compared 166 patients with vascular occlusion to 165 patients with no vascular occlusion (19).
However, despite the small numbers involved, this later study
showed that blood loss was significantly lower in those
patients who had vascular occlusion. A low CVP reduces
back bleeding from hepatic veins during the transection
(2022) and is now accepted practice during liver resection
worldwide. Indeed, following the introduction of low CVP
anesthesia in our own unit, the mean blood loss was significantly reduced from 2116 to 426 ml (3). However, these
techniques can test the patients cardiovascular reserve.
Obstructing the portal blood flow causes venous congestion
of bowel and in combination with warm ischemic liver
injury, releasing a flush of anerobic metabolites and cytokines back into the circulation on release of the clamp (23).
Low CVP anesthesia relies on patients being maintained in a

MANAGING COMPLICATIONS OF HEPATECTOMY


Table 7.3 Complications of Hepatectomy
General complications
Immediate
(on table)
Early (days)

Late (weeks/
months)

Specific complications

Hypothermia

Bleeding

Respiratory
atelectasis, pleural
effusion, pneumonia
Cardiovascular
DVT, PE, MI,
arrhythmias, CVA
Renal failure
Wound infection
Pain
Incisional hernia

Bleeding
Bile leak
Hepatic insufficiency
Intra-abdominal
abscess

Investigation and Treatment


The hemoglobin concentration and clotting screen should be
performed urgently, ensuring that the patient has an up-todate cross match. Any coagulopathy should be corrected. If the
patient remains shocked, appropriate investigations may
include endoscopy and mesenteric arteriography. Ultimately,
as in our own series, small number of patients may need to
return to the operating theatre for surgical control of
hemorrhage.

biliary complications
Biliary stricture

Abbreviations: DVT, deep vein thrombosis; PE, pulmonary embolus; MI,


myocardial infarction; CVA, cerebrovascular accident.

hypovolemic state until liver resection has been completed


(20,21). This is in contrast to most other major surgical procedures, where patients have large volumes of crystalloid and
colloid perioperatively.
While a recent meta-analysis has confirmed that the use of
the antifibrinolytic agent aprotinin can significantly reduce
transfusion requirements during liver transplantation (24),
there is no evidence for its routine use during liver resection
(25). In contrast, a prospective double-blind randomized
trial of tranexamic acid, another antifibrinolytic agent, has
shown that its use perioperatively significantly reduced the
blood loss and transfusion requirements in elective liver
resection (26). Two prospective randomized controlled trials
have failed to show any benefit of using recombinant factor
VIIa in either noncirrhotic (27) or cirrhotic (28) patients
undergoing hepatectomy.
Since the early 1990s, the use of fibrin sealants has become a
popular aid hemostasis at the hepatic parenchymal transection
site. Two early randomized trials suggested some benefit in
achieving hemostasis (29) and reducing postoperative blood
loss (30), although the numbers involved were small. A more
recent trial of a carrier-bound fibrin sealant (TachoSil) suggested it was quicker and more effective hemostasis compared
to argon beam coagulation (31). However, the numbers
involved were again small (<65 patients in each group). A
larger prospective randomized trial of fibrin glue versus control involving 300 patients undergoing hepatic resection was
published in 2007 (32). This showed no difference in blood
loss, blood transfusion, or overall morbidity between those
who received the fibrin glue and those who did not. This study
provides the best evidence to date that the routine use of such
topical hemostats is not justified, although it is our own personal bias that fibrin glue needs to be combined with a collagen matrix to be effective.
Presentation
Postoperatively, patients who are bleeding may present with
classical signs of shock, persistent blood loss in an abdominal
drain, a drop in hemoglobin, or gastrointestinal bleeding.

Incidence and Definition of a Bile Leak


Bile leak remains a persistent problem after hepatectomy, with
a reported incidence of 1% to 12% (3,33). In addition, it
appears to be the most common complication after living
donor hepatectomy, with an incidence of 7.5% in the 731
donors in one Japanese series (34) and 9% in 381 donors in an
American series (35). The variable incidence may be explained
by the different patient populations analyzed and the lack of
consensus regarding the definition. The Amsterdam group has
defined bile leakage as one or more of the following criteria:
the presence of persisting bile-stained effluent from an abdominal drain, leakage detected on radiological imaging, and
occurrence of a bile collection drained percutaneously or
found during relaparotomy (36). This definition of a bile leak,
used in conjunction with Claviens severity grading (13), could
be widely applied in clinical practice.
Prevention
Meticulous technique during the parenchymal transection,
ensuring that both small and large bile ducts are adequately
secured with clips, ties, or sutures, is vital for the prevention of
bile leakage. Inspection of the cut surface and application of a
clean white-gauze swab is usually enough to reveal a bile leak,
which must then be sutured. Methods for testing for bile leakage have previously been advocated and include injection of
the biliary system (usually via the cystic duct stump) with
saline solution or methylene blue, or formal direct cholangiography after the transection has been completed. However, the
only prospective randomized study has shown no evidence
that such maneuvers reduce the bile-leak rate (37) and thus
this technique cannot be recommended as a routine. While
one study has show that topical fibrin glue significantly reduces
the bile-leak rate following hepatectomy (38), other studies
have failed to show any benefit (29,39). Thus there is no clear
evidence that topical hemostatic agents used after the liver
resection on the parenchymal surface reduce the bile-leak
rate (33).
Risk Factors for a Bile Leak
There is consensus in the literature that extended hepatic
resections are associated with an increased risk of bile leak
(36). An Italian series of 610 liver resections without a concurrent hepaticojejunostomy reported a 3.6% incidence of postoperative bile leakage (38). On multivariate analysis, they
found that resection of a peripheral cholangiocarcinoma (relative risk 5.5) and hepatectomies including segment 4 (relative
risk 3.1) were the only independent risk factors for a bile leak.

65

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Other risk factors reported include a large transection area and
operations, which expose the major Glissonian sheath around
the hepatic hilum (major central resections including segments 4b, 5, or the caudate), with subsequent unrecognized
injury to the bile duct (40). Gertsch and coworkers showed
that patients who had postoperative ischemia of part of the
remnant liver had a higher incidence of bile leakage (18.4%)
compared to those with no ischemia (2.7%) (41). In addition,
any hepatic resection, which includes resection of the extrahepatic biliary tree with concomitant hepaticojejunostomy has a
significantly higher bile leak rate (36,40,42). The presence of
cirrhosis appears to be associated with a lower risk of a bile
leak, possibly because of a less aggressive surgical approach in
these patients (38).
Presentation of a Postoperative Bile Leak
A bile leak can present as bile-stained effluent from an abdominal drain. Other patients will show signs of intra-abdominal
sepsis, with a fever, abdominal pain, or right-sided chest signs,
and leak bile into a secondarily placed drain.
Management of a Postoperative Bile Leak
Minor bile leaks may often resolve with no requirement for
further intervention. In their case series, Vigano and coworkers found that 77% of bile leaks settled spontaneously. However, a drainage output greater than 100 ml on postoperative
day 10 was the only independent risk factor for failure of conservative management (43). Percutaneous tube drainage
should then be the intervention of choice. If percutaneous
drainage fails because of persistent or recurrent bile leakage,
endobiliary stenting should be undertaken, to reduce the
intrabiliary pressure and promote rapid resolution of the bile
leak (44,45). Clearly this can only be successful if there is
communication between the leaking bile duct and the main
biliary tree.
In the face of failure of percutaneous and endoscopic
approaches, relaparotomy should be undertaken, with a view
to optimizing drainage, a further hepatic resection, or formation of a biliary enteric anastomosis. The precise intraoperative decision will depend on the volume of the liver remnant
and functional liver reserve as well as the extent of local sepsis.
We have had to perform a biliary enteric anastomosis for a
persistent bile leak in one patient out of our entire cohort of
liver resections (1/1600). The patient had undergone an
extended left hepatectomy. Following an initially uncomplicated postoperative course with discharge home on day 4, she
was readmitted three weeks later with intra-abdominal sepsis.
After initial percutaneous drainage of a large bile collection,
the leak failed to resolve with endoscopic biliary drainage. A
laparotomy was therefore performed and the area of bile leakage identified at the resection edge, but no actual bile duct
seen. A Roux-en-Y jejunal loop was therefore anastomosed to
the resection edge with a successful outcome.
Consequences of a Bile Leak
The direct consequences of a postoperative bile leak include
prolonged hospital stay and increased morbidity and mortality (39). Patients with persistent bile leakage are at risk of

66

developing intra-abdominal sepsis, with the attendant risk of


liver failure and death (46).
Incidence of Biliary Stricture after Hepatectomy
A biliary stricture is an uncommon, late complication of hepatectomy, with an incidence of 0.2% (4/1803) in the SloanKettering series (6). It is caused by unrecognized intrahepatic
injury to the bile ducts, either directly or due to isolated devascularization of the biliary tree. A distal biliary stricture may be
responsible for a persistent proximal bile leak.
Management of Biliary Stricture After Hepatectomy
A biliary stricture after hepatectomy should be managed in the
same way as any iatrogenic biliary stricture. This will include
radiological and/or endoscopic assessment of the level of the
stricture and its relationship to the remaining biliary tree,
together with an estimate of the volume and function of the
hepatic remnant. Avoidance of sepsis or cholangitis is paramount, as is attention to the nutritional status of the patient.
Potential treatments include endobiliary stenting, biliary
reconstruction, or a further hepatic resection tailored to the
individual circumstances.

hepatic insufficiency
Definition and Incidence
There is currently no internationally accepted definition of
postoperative liver failure or hepatic insufficiency. Belghitis
group have proposed the 50-50 criteria, which are a prothrombin index <50% of normal (corresponding to an International Normalized Ratio (INR) of 1.7 or more) and a
serum bilirubin > 50 mol/L on postoperative day 5, as a
simple, accurate predictor of liver failure and death (47). On
the fifth postoperative day, both prothrombin time and bilirubin should have returned to normal values. They found
that the persistence of the 50-50 criteria at this time indicated a significant impairment of liver function and was
associated with a 59% risk of early postoperative mortality,
compared with a 1.2% risk if the criteria were not met. They
recently prospectively evaluated these criteria in a cohort of
436 elective hepatectomies and found that the 50-50 criteria on postoperative days 3 and 5 were accurate predictors of
death on multivariate analysis (48). The MD Anderson group
reviewed data from 1059 noncirrhotic patients who underwent a major hepatectomy and found that a peak bilirubin of
more than 120 mol/L (7.0 mg/d/L), accurately predicted
liver-related death and suggested that this be used as a definition (49). By this definition, the incidence of postoperative
liver failure with or without multiorgan failure resulting in
death in their series was 2.8%. In the French multicenter
series of 1568 hepatectomies, the incidence of liver failure
was 43/1568 (2.7%), however this was responsible for death
in 7/43 (16%) of those patients (50). In the Hong Kong series
(8), postoperative liver failure occurred in 47 out of the
1222 hepatic resections (3.8%), but again, it is not defined.
This series had a higher incidence of patients (59.2%) with
cirrhosis or chronic hepatitis compared to most Western case
series. Overall, the reported incidence in the literature ranges
from 0.7% to 9.1% (51).

MANAGING COMPLICATIONS OF HEPATECTOMY


Prevention
The incidence of postoperative liver failure is related to the
volume and quality of the remnant liver, the amount of blood
lost during surgery (52,53), and the presence of comorbid
conditions such as diabetes mellitus (51,52). As treatments are
limited and the consequences life-threatening, preoperative
assessment of the individual patients risk is vital and will
affect the operative approach (54). Assessment of liver function can be achieved using liver biochemistry, coagulation
studies, and the ChildPugh classification (55). However,
because of the limits of the ChildPugh scoring system, surgeons have looked for other tests of hepatic function to help
identify patients at risk of postoperative liver failure. The indocyanine green (ICG) retention test is the most widely used in
clinical practice. ICG is a dye that is removed from plasma by
the liver and rapidly excreted unchanged into bile. The ICG
retention rate at 15 minutes (ICGR-15) provides a measure of
hepatic function, with clearance said to be impaired when
15% or more of the ICG remains within the plasma at 15 minutes (56). Makuuchis group has successfully incorporated the
ICGR-15 in their preoperative work-up of ChildPugh class A
patients to guide the extent of resection (54). The Hong Kong
group also uses it in their preoperative assessment of patients
with HCC, because of their high incidence of chronic liver disease. They use an ICGR of <20% as a cut-off for a major resection in cirrhotic patients (57).
There is a close relationship between liver function and volume. The volume of the future liver remnant (FLR) may be
assessed by computed tomography (CT) volumetry. Vauthey
and colleagues reported the value of residual liver volume using
CT as a predictor of hepatic dysfunction, noting a critical value
of 25% below which they found a significant risk of hepatic
dysfunction in patients with no underlying liver disease (58).
These data have been confirmed by two other groups, who
defined a critical FLR of 26.6% (53) and 26.5% (59), respectively. In patients with underlying liver disease, such as chemotherapy-associated steatohepatitis or cirrhosis, the FLR should
be greater (59), with Vautheys group suggesting it should be at
least 30% if the patient has received extensive preoperative chemotherapy and 40% if they have cirrhosis (60). A recent systematic review (61) looked at the association between
chemotherapy type, liver injury, and the impact of liver injury
on outcome following liver resection. This study found a significant association of irinotecan with steatohepatitis, especially in obese patients. These patients had a higher 90-day
mortality rate compared to patients who did not have steatohepatitis (15% vs. 2%, p = 0.001) and a significantly higher risk
of death from postoperative liver failure (6% vs. 1%, p = 0.01),
highlighting that irinotecan appears to impair the functional
reserve and regenerative capacity of the liver (60). Chemotherapy-associated hepatotoxicity and its impact on outcome after
hepatectomy are covered in more detail in chapter 17.
The use of portal vein embolization (PVE) to improve
volume of the FLR and as a functional test of hepatic reserve
PVE can be used to induce hypertrophy of the FLR and reduce
the incidence of postoperative complications, including liver
failure, in patients with a marginal FLR (6265). PVE may also

provide an important functional test of hepatic reserve in


patients with a borderline FLR, with the degree of hypertrophy
predicting outcome from hepatectomy (63). Certainly, if
patients with borderline FLR remnants do not exhibit hypertrophy following PVE, they should not undergo hepatic resection because of the risk of postoperative liver failurethe
so-called trial of PVE. A recent consensus statement suggests
that PVE is indicated when the FLR is <20% in patients with
normal liver, <30% in patients who have had chemotherapy,
and <40% in patients with well-compensated cirrhosis (66).
Optimization of Venous Drainage
A key aspect of maximizing the function of the remnant liver
and prevention of hepatic insufficiency is to preserve and optimize its venous drainage. Belghiti showed that following a
right hepatectomy, left hepatic venous outflow was impaired if
the left liver was not fixed in the anatomical position (defined
as the position where the falciform ligament was in its strict
medial position) (67). The consequent venous congestion
could result in bleeding from the resection surface in the
short-term and impaired function and regeneration of the
liver remnant in the ensuing few days or weeks.
The venous drainage on preoperative imaging should be
carefully evaluated when planning any resection, therefore
allowing optimization of the venous drainage of the future
liver remnant. For example, preserving the umbilical vein
when performing a right hepatectomy extended to segment 4a
will allow adequate drainage of segment 4b. Belghitis group
has demonstrated the importance of this, using the living
donor hepatectomy as a model (68). They showed that 84% of
donors who underwent right liver harvesting to include the
middle hepatic vein, developed venous congestion of segment
4 postoperatively, compared to none of the donors who had
right liver harvesting without including the middle hepatic
vein. Furthermore, this was associated with impaired postoperative liver function and regeneration.
Treatment of Postoperative Hepatic Insufficiency
As emphasized above, the mainstay of management of operative hepatic insufficiency is prevention. However, should it
occur, there are a number of important strategies to employ.
Patients should be receiving best supportive care, to optimize
other organ functions, in a minimum level 1 environment,
with intensive escalation of care as required. It is important to
avoid secondary septic insults such as pneumonia or intraabdominal sepsis, as any second hit will increase the risk of
death. Liver failure and sepsis appear to be closely linked.
Schindl and coworkers have reported a direct correlation
between the extent of liver resection and the incidence of
infective complications (53). This risk is further increased in
the presence of cirrhosis or liver failure (53). Thus in a patient
developing liver failure, infectious complications should be
actively excluded by clinical assessment and radiological
and bacteriological investigations. Infectious complications
should be aggressively treated with appropriate antibiotics
and drainage or reoperation as required.
Other management strategies to combat posthepatectomy
liver failure include dietary sodium restriction (<90 mmol

67

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


sodium per day), to reduce the sodium retention that can occur
as a result of decreased renal excretion and enhanced sodium
resorption (69). Some patients will develop hyponatremia and
worsening ascites due to water retention. It is our practice to
moderately restrict fluid for such patients to 1.5 to 2 L per day.
If the serum sodium is > 126 mmol/L, patients should be commenced on spironolactone, an aldosterone antagonist, which
acts on the distal tubules to increase natriuesis and conserve
potassium. The initial dose should be 50 to 100 mg per day,
increased up to 400 mg per day and limited by the development
of hyperkalemia. The additional use of frusemide, a loop
diuretic, at a dose of 40 mg per day, can enhance its natriuretic
effect. In patients with a serum sodium 121 to 125 mmol/L, clinicians should consider stopping diuretics, particularly if there
is evidence of renal impairment. In this scenario, patients
should be given volume expansion, ideally with 20% salt-poor
albumin. Other volume expanders such as Gelofusine and
4.5% albumin solutions contain high concentrations of sodium
(154 mmol/L) and their use will potentially worsen patients
sodium retention. The management of patients with a serum
sodium < 120 mmol/L is difficult and controversial. In this scenario, all diuretics should be stopped and patients should
undergo volume expansion with colloid or saline. It is important that these patients are not taking nonsteroidal antiinflammatory drugs (NSAIDs), as these can also inhibit salt and water
excretion and compound the problem (70,71). Hypoglycemia
and hypophosphatemia should be aggressively corrected. These
recommendations from the evolution of our own practice are
reinforced by the current U.K. guidelines on the management
of ascites in cirrhosis (69).
A few small case series suggest that artificial liver support
systems such as the molecular-adsorbent recirculating system
(MARS) may be of value in treating posthepatectomy liver
failure (72). However, a recent systematic review showed that
there is currently insufficient evidence to support their use in
these patients (73).

intra-abdominal infection
Importance and Incidence
Posthepatectomy infections are important as they can precipitate liver failure and death, as discussed earlier. The incidence
of infected perihepatic collections ranges from 2.7% to 6.1% in
modern case series (6,8), but is higher (12.8%) in older series
(74). The incidence of infected ascites is less than 1% (8).
Factors Affecting the Incidence of Intra-abdominal Infection
The decreasing incidence of intra-abdominal infections over
time is a reflection of the evolution of liver surgery in the past
30 years. In Yanagas series of 149 liver resections performed
between 1973 and 1984, 19 patients (12.8%) developed intraperitoneal septic complications, of whom 13 patients died of
liver failure (74). They identified five risk factors for this,
which were: (1) right or extended right hepatectomy, (2) age >
65 years, (3) operation time > 5 hours, (4) blood loss > 3L, and
(5) postoperative bleeding, which required a laparotomy to
achieve hemostasis. A further Japanese case series of 535 hepatectomies performed between 1992 and 2005 reported that
advanced age, diabetes mellitus, the use of silk sutures, and bile

68

leakage were all associated with postoperative infective complications (75). They show a reduction in their postoperative
infection rate from 44.7% at the start of the study to 9.2% by
the end, with improvements in clinical practice such as early
enteral nutrition and aggressive management of bile leaks.
There is no evidence that the use of postoperative systemic
antibiotics reduces postoperative infective complications. In a
prospective randomized trial, Wu and coworkers showed that
postoperative systemic antibiotics after liver resection did not
influence the incidence of infective complications, which was
23% in each group (76). Another prospective randomized trial
investigated whether omentoplasty to the hepatic parenchymal transection surface reduced the incidence of deep abdominal complications (bleeding, hematoma, infection with or
without purulent discharge through drains, or bile leakage).
The authors found that while deep abdominal complications
were significantly associated with major hepatic resections,
omentoplasty did not reduce their incidence (77).
Abdominal Drainage
The use of routine drainage after liver resection and its role
in preventing complications remains controversial. A prospective randomized trial involving 186 patients compared
closed suction drainage with open drainage after elective
hepatectomy. The trial showed that the incidence of infected
subphrenic collections, postoperative ascites, and pleural
effusion was significantly lower in the closed suction drainage group. However, both groups showed similar rates of
subphrenic hematoma and biloma formation (78). In contrast, another trial prospectively randomized 120 patients
undergoing elective hepatectomy to closed suction drainage
or no drainage (79). This showed no difference in overall
complication rate between the two groups. However, 18% of
patients in the no drainage group subsequently required a
percutaneous drain, compared to 8% in the drained group,
but this was not statistically significant. The authors concluded that routine drainage was unnecessary after elective
hepatectomy and adopted a selective drainage policy. A trial
from Hong Kong, which randomized 104 patients with
chronic liver disease to closed suction drainage or no
drainage, showed that there was significantly higher morbidity in the drainage group (73%) compared to the no drainage
group (38%) (80). Further, specifically there was a higher
incidence of wound complications in the drainage group and
a trend towards more septic complications.
In conclusion, elective closed suction drainage in patients
with chronic liver disease is not recommended. For all other
patients, there is no evidence that routine abdominal drainage
prevents postoperative abdominal septic complications. However, for patients at high risk of bile leakage (as outlined earlier
in this chapter), routine drainage is recommended.

respiratory complications and pain relief


Incidence
Respiratory complications such as pleural effusion and bronchopneumonia are common after hepatectomy. In the Hong
Kong series, 7% of patients developed a postoperative pneumonia and 5% of patients had a pleural effusion requiring

MANAGING COMPLICATIONS OF HEPATECTOMY


aspiration (8). In the Sloan-Kettering series of 1803 resections,
the corresponding incidence was 3% pneumonia and 8.5%
symptomatic pleural effusion; 2.5% of patients had basal atelectasis, with a further 2.5% developing respiratory failure
requiring support. In addition, 1% of patients suffered a pulmonary embolus postoperatively (6).
Prevention and Management
As with any abdominal operation, a patients risk for respiratory complications should be assessed preoperatively. Smokers
should be encouraged to stop. Patients with chronic lung disease should have aggressive preoperative physiotherapy. Good
postoperative pain relief to facilitate early mobilization, deep
breathing, and coughing is paramount. Epidural analgesia is
one of the best methods for provision of postoperative pain
relief in patients recovering from major upper abdominal
operations (81,82). However, the procedure itself is associated
with complications such as hypotension, bradycardia, immediate or delayed respiratory depression, urinary retention,
dural puncture and hematoma, and/or infection within the
spinal cord. Furthermore, patients undergoing hepatectomy
are at risk of a prolonged prothrombin time postoperatively
and this may affect the timing of removal of the epidural catheter (83). A retrospective review of 367 patients who underwent elective hepatectomy showed that patients who had
epidural analgesia had a significantly lower mean arterial
blood pressure in the theater recovery area and were more
likely to have a blood transfusion during their hospital
course (84). Thus in our unit, for the past five years, we have
moved away from epidural anesthesia to using a continuous
intermuscular bupivacaine infusion combined with patientcontrolled analgesia (85). This is a safe, simple, and efficacious
method of providing postoperative pain relief in patients after
liver resection and is associated with a low incidence of pulmonary complications (85).
To prevent the small but potentially fatal risk of thromboembolic complications, all our patients wear graduated compression stockings. Pneumatic foot pumps are worn in the operating
theatre and continued until the patient is fully mobile. Lowdose subcutaneous low-molecular-weight heparin is given
daily postoperatively, once the prothrombin time has returned
to within three seconds of normal.
When respiratory complications do occur, they should be
managed aggressively and proactively to minimize the risk of
sepsis precipitating hepatic insufficiency.

cardiac complications
In our own series, the Sloan-Kettering and the Hong-Kong
series, the most common cardiac complication of hepatectomy
is arrhythmia, with an incidence of 2% to 5% (6,8). Myocardial
infarction and heart failure will also occur in about 1% of
patients. At-risk patients should be identified preoperatively
and undergo a cardiac assessment with exercise or pharmacological stress echocardiography and coronary angiography. Cardiac function should be optimized preoperatively with medical
therapy, coronary stenting, and coronary artery bypass grafting
as required. We have also used a perioperative intra-aortic
balloon pump (86).

Patients who develop cardiac complications following


hepatectomy should be managed in conjunction with the local
cardiologists. If required, aspirin, clopidogrel, and formal anticoagulation with heparin can be given within days of a hepatectomy, although it is advisable to avoid the administration of
a large loading dose of warfarin, to minimize the risk of early
secondary hemorrhage.

renal failure
Definition and Incidence
Renal failure is defined as the need for renal replacement therapy. Studies have shown that 3% to 7% of patients require
renal replacement therapy after liver resection (21,87). In our
own case series, the incidence is 0.9% (unpublished data).
Etiology of Renal Failure After Hepatic Resection
There are three main factors which may contribute to the
development of renal failure following liver resection. Elderly
patients and those with conditions such as hypertension,
atherosclerosis, or chronic kidney disease are at risk (88).
These patients have a reduced capacity for neurohumoral
autoregulation of glomerular blood flow during surgery and
thus an increased risk of acute tubular necrosis (ATN) (88).
Perioperative use of NSAIDs may also impair normal autoregulation of glomerular perfusion through inhibition of
arteriolar dilatory prostaglandins (88) and should be avoided
in patients with preoperative renal impairment. The second
factor relates to the hit of surgery. Two key factors in the
pathogenesis of ATN are hypovolemia and renal damage by
inflammatory mediators (87). Both these events are predictable in every hepatic resection that employs low CVP anesthesia and portal inflow occlusion. Obstruction of the portal
blood flow with the Pringle maneuver causes splanchnic
venous congestion and, in combination with warm ischemic
liver injury, results in a flush of anerobic metabolites and
cytokines into the systemic circulation on release of the
hepatic inflow clamp (23). Low CVP anesthesia relies on
patients being maintained in a hypovolemic state until liver
resection has been completed (20,21). This is in contrast to
most other major surgical procedures, where patients are
given significant volumes of crystalloid and colloid in the
perioperative period. Moreover, vasodilators are often used
to further reduce the CVP, leading to distributive changes in
blood flow (20). Certainly, low CVP anesthesia with or without hepatic inflow occlusion can produce major circulatory
changes, potentially resulting in ATN and subsequent renal
impairment or failure (87). Another factor, which contributes to the etiology of renal failure following liver resection is
a low perfusion state either secondary to cardiac dysfunction
or distributive circulatory changes, such as sepsis or hepatorenal failure (87,88). Postoperative renal dysfunction is
often multifactorial.
Consequences of Postoperative Renal Failure
The potential consequences of acute kidney injury include
increased risk of mortality and may contribute to the
development of chronic kidney disease (89).

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Hepatectomy in Patients with Preoperative
Renal Impairment
Patients with preoperative renal impairment, as defined by a
raised preoperative serum creatinine, are at increased risk of
both renal and non-renal complications (6). These patients
require careful monitoring in the early postoperative period in
order to optimize fluid balance and cardiac output and in
some instances may require hemofiltration.

wound complications
The incidence of wound infection was 5.2% in the SloanKettering series, with a further 10 patients (0.5%) having a
wound dehiscence (6). The Hong Kong series of 1222 liver resections reports double these complication rateswith 115 patients
(9.4%) developing a wound infection and 16 patients (1.3%)
suffering wound dehiscence (8). An explanation of the higher
incidence of wound complications in the Hong Kong series may
be their higher percentage of cirrhotic patients (33% vs. 9%).
A study from Japan of 626 liver resections, with a 7.7% incidence of incisional hernias, examined the risk factors for this
(90). Risk factors included the type of incision, with a reversed
T incision having a significantly higher incidence of an incisional hernia (21.7%) compared to midline (6.3%), J-shaped
(4.7%), or a right transverse incision with long midline extension (5.4%). Furthermore, postoperative ascites, body mass
index, repeat hepatectomy, and steroid use were also significant risk factors. The incidence of reported incisional hernia
was 0.2% in our own series, with the two known patients who
developed incisional hernias undergoing repair of these at the
time of repeat liver resection. We believe this low incidence is
related to the method of closure of the J-shaped wound, with
a tension-free, 2-layer closure, using a 6:1 suture (looped
0-nylon) to woundlength ratio, as opposed to the traditional
4:1 ratio (85).

conclusions
The safety of elective liver surgery has improved dramatically
in the past 30 years, despite ever-widening indications for
hepatectomy. However, complications still happen and prevention is the key to minimizing their incidence. When complications do occur, they should be aggressively managed, in a
high-dependency environment, by a multidisciplinary team.
International consensus regarding definitions of complications and a severity classification is still required.

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Pancreatic resection
Thilo Hackert, Moritz Wente, and Markus W. Bchler

background
Pancreatic cancer remainswith an overall long-term survival rate of less than 1%one of the most difficult cancers to
treat. It is the fourth leading cause of cancer-related mortality
in the Western world and is responsible for around 30,000
deaths per year in the United States and 65,000 per year in
Europe (1,2). In only 10% to 20% of pancreatic cancer patients
potentially curative surgery is possible, and even in these
patients, the median survival is only 10 to 18 months with
5-year survival rates of approximately 20% to 25% (3,4).
Nonetheless, surgery remains the only treatment option with
the chance of cure. Pancreatic surgery has significantly changed
during the past few years. Irrespectively, pancreas resections
remain an intervention of particular significance, often technically challenging and with high logistic demands for preoperative diagnostics and perioperative management. Recently, the
value of centralization of pancreatic surgery in high volume
institutions has been demonstrated. The current mortality
rates following pancreatic resections are well below 5% in specialized surgical centers (5,6).

standard resections
Whipple Resection
Partial Pancreaticoduodenectomy (Whipple resection) with or
without distal stomach resection is the surgical option for
tumors of the pancreatic head, which account for the majority
of pancreatic cancers (Fig. 8.1). Pylorus-preserving pancreaticoduodenectomy has been proven to be equal to the classical
pancreaticoduodenectomy in terms of tumor recurrence or
long-term survival, and should therefore be considered the standard procedure for tumors of the pancreatic head (7). Key steps
of the surgical procedure are the postpyloric division of the duodenum, which is usually carried out by use of a stapling device
andmeanwhile common in many centersthe supracolic
division of the ascending duodenum as soon as this portion is
reached during resection. This modification facilitates the resection procedure and allows manual control of the pancreatic head
without switching positions between the supra- and infracolic
department. Division of the pancreas is done sharply above the
superior mesenteric vein after this has been tunneled to make
sure that the vein is not injured during resection and that the dissection can be done without vein replacement (see below).
After removing the specimen, tumor-free resection margins
should be confirmed intraoperatively by frozen sections of the
cut end of the bile duct and the cut end of the pancreatic remnant. Bleeding control along the pancreatic dissection margin
is achieves by carefully stitching single bleeding sites with
monofilament and nonabsorbable sutures. The pancreatic
duct must be seen and protected during this procedure. During pancreaticoduodenectomy, a standardized lymphadenectomy needs to be carried out. This includes the complete

dissection of the hepatoduodenal ligament, the lymph nodes


along the common hepatic artery, portal vein, and the cranial
portion of superior mesenteric vein as well as dissection of the
right-sided lymph nodes of the celiac trunk and along the
right side of the superior mesenteric artery (Fig. 8.2). Today,
we have good evidence that there is no benefit for a more
extended approach of lymphadenectomy. Meta-analysis from
four randomized controlled clinical trials has shown no survival benefit after extended lymph node dissection but has
demonstrated a significant increase in surgical morbidity (8).
Completion of the dissection can then be done from the infracolic aspect by removing the first jejunal loop (2025 cm) to
ensure tensionless mobility of the next loop that is used for the
following reconstruction and is transposed into the right
upper quadrant transmesocolically.
One of the most important operative steps to prevent severe
postoperative complications is the pancreaticojejunostomy.
We prefer to perform this anastomosis end-to-side in a twolayer fashion stitching the pancreatic duct separately (Fig. 8.3).
Using this technique, insufficiency rates of less than 3.5% can
be achieved (9,10). Bile duct reconstruction should be standardized as well to avoid leakage or postoperative bile collections. Although this complication is less frequent than
pancreatic fistula, it may cause severe and long-lasting complications. An approach that can be performed even in technically challenging situations with small and deep ducts is the
single-stitch distant suture of the posterior wall by a one-layer
technique completed by single stitches of the anterior wall.
Finally, an end-to-side duodenojejunostomy completes the
reconstruction. Recent studies have shown that an antecolic
reconstruction is much more favorable in terms of delayed
gastric emptying (1,12).
Drain placement seems to be another essential step at the
end of the operation as there has been growing evidence that
pancreatic leakage can be recognized and severe complications
caused by intra-abdominal pancreatic fluid collections can be
prevented by adequate drain positions. As there may be need
for a long-lasting maintenance of intra-abdominal drains in
case of fistulas, soft silicon drains should favorably be used.
Drain removalwhich can usually be done 48 hours postoperativelyshould be preceded by analysis of pancreatic
enzyme levels in the drain fluid. Amylase levels of more than
5000 iU/ml seem to represent a cutoff value for the recognition of pancreatic fistulas and should therefore be respected
carefully (1317).
Distal Pancreatectomy
Distal pancreatectomy is performed for tumors in the body or
tail of the pancreas and includesdepending on the dignity of
the underlying tumortotal splenectomy. From the surgical
point of view, tumors above or on the left side of the superior

73

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

Figure 8.1 Partial pancreaticoduodenectomy. Classical Whipple resection (left) and pylorus-preserving modification (right).

Figure 8.2 Intraoperative situs after partial pancreaticoduodenectomy. Pancreatic remnant with probe introduced, dissected portal vein and hepatic
artery. A jejunal loop is prepared for the pancreaticojejunostomy.

mesenteric vein are suitably located for this procedure. Dissection of the pancreas is performed above the vein after tunneling and lifting up the body of the gland. The dissection
itself can be done sharply or by using a stapling device, preferably with a thickness-adopted adjustment of the stapler. To
date, there are no high-power studies to support either procedure. In case of sharp dissection, we prefer a V-shaped transection line. As in other resections, tumor-free resection margins
should be examined by intraoperative frozen section. The pancreatic duct is separately closed by a monofilament Z-shaped
nonabsorbable suture and the transection line can afterward
be closed by single stitches covering the complete margin by
pancreatic capsular tissue. There is no need or evidence for any
further covering of the resection margin by sealants or
patches (18). This procedure implies a certain limitation concerning the extent of distal resection toward the head of the

74

pancreas. The larger the tissue area of the transected parenchyma gets, the more difficult it gets to close the parenchyma,
which is associated with increased fistula rates. Therefore, the
right margin of the superior mesenteric vein represents the
limit to which a safe surgical closure of the pancreatic remnant
can be performed. In case of transection by a stapling device,
this limitation is technically implied by the length of the stapler line. No additional sutures are necessary after stapler dissection. Despite all approaches, fistula development after distal
pancreatectomy remains an unsolved problem. Fistula rates
range from 12% to 40% (8,19). To address this clinical problem, remnant closure by sutures after sharp dissection is currently compared to stapler dissection in a randomized
controlled study (DISPACT trial) in a multicenter approach
including 21 European centers and 360 patients by February
2009 (20). A spleen-preserving distal pancreatectomy can be
performed in benign lesions or intraductal papillary mucinous neoplasias (IPMNs), if the splenic vessels are not involved
in the tumor or cystic process. However, there are no clear
advantages in preserving the spleen in adult patients (21). Possible advantages could be infection prophylaxis, less operative
blood loss, fistula rates as well as fewer thromboembolic complications (22,23). By contrast, the risk of splenic infarction
and portal hypertension has to be regarded whenever the
spleen is preserved. From the currently available literature
mainly retrospective studiesnone of these parameters is
clearly proven, further studies have to address this topic in the
future. By contrast, there is growing evidence that distal pancreatectomy can be performed with good results laparoscopically. This approach is usually performed using 5 trocars and
stapler dissection of the pancreas. It is routinely performed in
several centers with results comparable to the open approach
in terms of operative morbidity and outcome (23). The possible advantages of laparoscopic operations, with faster patient
recovery, less pain medication, and better cosmetic results are
currently evaluated in larger series.
Total Pancreatectomy
The concept of total pancreatectomy has to be divided into the
rescue procedure in not conservatively managed postoperative

PANCREATIC RESECTION

Figure 8.3 Pancreatico-jejunostomy. Preparation of duct sutures (upper left), position of the jejunal loop (upper right), anterior wall sutures (lower left), and
completed anastomosis (lower right).

complications caused by the pancreatic remnant after head


resections and the primarily performed total removal of the
gland with or without the spleen (24). Completion pancreatectomy may be necessary in case of severe complication like
insufficiency of the pancreaticojejunostomy with septic or
bleeding complications. In this situation, an early completion
operation can be life-saving for the patient and is technically
similar to a distal pancreatectomy after disconnection of the
pancreas anastomosis (25,26). Primary total pancreatectomy
can be required in patients with a nonaltered pancreatic remnant due to the soft tissue texture, e.g., in distal bile dust cancer
or duodenal tumors without congestion of the pancreatic
duct, which can make the pancreatic anastomosis a dangerous
reconstruction. The surgeon has to evaluate the costbenefit
relation carefully; in doubtful situations a risky anastomosis
should rather be avoided. From the oncological point of view,
extensive main-duct IPMNs, IPMNs with progression to
carcinoma, familial or multifocal pancreatic cancer are indications for a primary total pancreatectomy. Furthermore, this
procedure may be necessary if a tumor-free resection margin
and R0 situation cannot be achieved otherwise (2429). The
resection can be performed as a two-part procedure with an

initial head resection similar to a Whipple procedure followed


by the distal resection, which facilitates the surgical preparation, or with a removal of the gland as a complete specimen,
if a pancreatic transection implies the risk of tumor cell spilling. Whenever possible, a pylorus-preserving reconstruction
should be preferred.
Duodenum-Preserving Pancreatic Head Resection
The best technique for the surgical treatment of pancreatic
head lesions in chronic pancreatitis is still under debate. Partial pancreatoduodenectomy with or without preservation of
the pylorus have served for many years as the primary surgical procedure. However, these resections are unsatisfactory in
terms of late morbidity with an incidence of up to 48% of
postoperative diabetes mellitus (30). Today, duodenumpreserving pancreatic head resection duodenum-preserving
pancreatic head resection (DPPHR), which was introduced
by Beger in 1972 (31), has undergone several modifications
and is considered the standard procedure for nonmalignant
head lesions in chronic calcified pancreatitis (32). Whenever
possible, depending on the extent of the calcified and fibrotic
lesions, the Berne modification as the most tissue-sparing

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


approach should be performed (Fig. 8.4). The surgical
procedure starts with an extensive Kocher maneuver of the
pancreatic head to palpate the head of the pancreas and
achieve bleeding control by compression during the resection phase. The anterior aspect of the head should be prepared under dissection of the right gastroepiploic vessels and
ligation of the gastroduodenal artery to minimize blood loss
during excision of the head. It is not necessary to tunnel the
pancreas above the mesenteric vein, especially as this is often
difficult due to the chronic inflammatory adherence of the
parenchyma. The resection margin should be defined by circular sutures around the altered tissue area. Afterward, the
head is sharply excised manually to control bleeding and perforation of the posterior parenchyma layer. All fibrotic and
calcified tissue should be removed and the pancreatic duct
has to be opened and inspected to extract stones and ensure
free drainage into the resection cavity. Special attention has
to be paid to the bile duct. In case of preoperative cholestasis
and/or preceding stents, the bile duct needs to be opened by
a T-shaped incision and the orifice should be fixed in the

Figure 8.4 Pylorus-preserving pancreatic head resection (Berne modification). Note the incision and fixation of the bile duct in the resection cavity.

resection cavity to avoid postoperative recurrence of bile


duct stenosis (33). Hemostasis in the resection cavity is
achieved by selective single stitches with nonabsorbable
sutures. The operation is completed by an anastomosis with
a Roux-Y-transected jejunal loop in a side-to-side fashion by
a two-layer running suture (Fig. 8.5). As in all other resections, drainage placement is important to monitor postoperative secretion and recognize possible fistula development
soon. the DPPHR procedure is widely accepted nowadays
and has proven to be equally efficient as the Whipple procedure in terms of long-term pain relief, overall morbidity and
mortality combined with significantly less intraoperative
blood replacement, shorter hospital stay, more postoperative
weight gain, less exocrine insufficiency, better occupational
rehabilitation, and quality of life in randomized controlled
trials and a recent meta-analysis (3237).
Segmental Resection
Segmental resections of the pancreas can be performed in
benign lesions located in the body of the gland (38). Surgical
technique includes a careful mobilization of the pancreatic segment under clipping of vessels followed by sharp dissection of
the defined segment. Afterward, reconstruction was done by
two-layer sutured anastomosis toward the tail of the pancreas
similar to the Whipple anastomosis and V-shaped closure of the
dissected margin toward the pancreatic head comparable to the
left resection technique. In case of extended resections toward
the head leading to a large resection margin, this can additionally be sealed with a seromuscular patch using the jejunal loop
that has been anastomosed onto the pancreatic tail before. No
fibrin glue or other sealants are required. At present, fistula rates
between 8% and 63% are reported, which shows the heterogeneity of the present studies (3841). However, a surgical mortality of 2% shows that segmental resections can be performed
safely and offers a useful tissue-sparing tool in selected patients.
Enucleation
Especially benign tumors, cystic lesions or IPMNs do not
necessarily require extensive pancreatic resections to

Figure 8.5 Pylorus-preserving pancreatic head resection (Berne modification). Resection cavity with first layer of the posterior wall of the pancreaticojejunostomy
(left), completed anastomosis (right).

76

PANCREATIC RESECTION
achieve surgical cure. Limited resections represent a tissuesparing treatment option to minimize the risk of exocrine
or endocrine pancreatic insufficiency postoperatively (42)
and to reduce surgical morbidity and mortality by reduced
operative trauma. One of the most important aspects to
perform an enucleation successfully is the accurate localization of the tumor or cystic lesion. Besides preoperative
localization by CT or MRI scan, the most important tool
for tumor location is the experience of the surgeon performing the exploration (4346). Mobilization of the pancreas is essential when tumors or cystic lesions have to be
located to enable a careful digital examination of the suspected lesion. This should be supplemented by intraoperative ultrasound to exclude multifocal tumorous lesions
especially in endocrine tumors or IPMNs. In addition, a
possible relation to the pancreatic duct can only be clarified
by ultrasound examination, if there is any doubt about it
intraoperatively (47).
A tumor size of 2.5 cm in diameter can be regarded as the
limit for a safely performed enucleation. Tumors measuring
more than 2.5 cm in size show malignant histological changes
significantly more frequently, making a local surgical approach
impossible. Besides, tissue trauma and wound surface following an enucleation reach a critical size for development of fistulas or other complications including bleeding or postoperative
pancreatitis (47). Enucleation itself is performed by careful
dissection along the tumor under clip ligation or stitching of
vessels supplying the lesion (Fig. 8.6). There is no evidence for

Figure 8.6 Tumor enucleation in the body of the pancreas.

any sealant or glue application after completing of the enucleation. Drain placement is essential as currently fistula rates of
approximately 20% are reported (48), most of them, however,
clinically uncomplicated.

exceptional indications
Vessel Resections
A common problem in pancreatic head resections is tumor
adherence to the superior mesenteric or portal vein. Today,
portal vein resection has become an established procedure and
can be carried out with morbidity rates of that are comparable
to standard Whipple procedures (4956). Portal vein resection
can be performed as a tangential resection with a direct suture
or a patch reconstruction. In cases where a segmental resection
is required due to a more extensive tumor adherence, either a
direct anastomosis or the interposition of an autologous venous
graft such as the saphenous vein or an allograft, e.g., a gore-tex
tube. In case of a primary anastomosis, it is essential to mobilize the mesenteric root completely, which implies the complete
mobilization of the right hemicolon. After this preparation, a
tension-free reconstruction of defects up to 3 cm length is usually possible. The anastomosis is performed as a running suture
of the posterior and anterior vessel wall with two 5-0 or 6-0
nonabsorbable sutures. When defects cannot be reconstructed
by the patients vein alone, a size-adopted graft should be
inserted in a similar end-to-end manner (52). Kinking of any
venous anastomosis must be avoided to prevent intra- and
postoperative vein or graft thrombosis with consecutive failure
of the bowel circulation. In certain situations, it may be helpful
not only to minimize the time of intraoperative occlusion of
the mesenteric/portal vein but also to clamp the superior mesenteric artery for this period to avoid venous congestion and
swelling of the small bowel and the right hemicolon (Fig. 8.7).
Arterial resection is a rather uncommon surgical procedure during pancreatic cancer resection. If the superior mesenteric artery is involved in the tumor process, this is a
general exclusion criterion for resection and has only been
reported in few patients (56). By contrast, tumor adherence
or infiltration along the celiac axis must not be considered as
generally irresectable (43,53). In selected patients, the celiac
trunk might be resected down to its aortic orifice in Whipple
as well as in left resection or total pancreatectomies (5456).
As long as the proper hepatic artery can be preserved, a
reconstruction is possible. The left gastric and splenic artery
can usually be cut without reconstruction, a consecutive

Figure 8.7 Examples of portal vein resections. Direct end-to-end anastomosis (left) and graft implantation (right).

77

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


splenectomy may be necessary in some patients. Restoration
of the hepatic perfusion must be ensured by re-anastomosing
the proper or common hepatic artery. This reconstruction
can be done with an interposition of any arterial vessel of the
celiac axis or a venous interposition graft. However, the arterial perfusion of the liver should be controlled by regular
duplex examinations and restored aggressively in case of a
vessel occlusion. Arterial hepatic perfusion failure may otherwise cause acute problems postoperatively in terms of liver
ischemia, necrosis, and infection and is a risk factor for bile
duct-associated complications in the long-term follow-up
(54,55). Yet, it needs to be mentioned that there are no larger
patient series on arterial resections in pancreatic surgery.
Therefore, this procedure can be carried out safely in experienced hands but is not based on high-quality scientific data
and outcome studies so far.
Multivisceral Resections
There are several studies (5760) on the outcome after multivisceral resection for pancreatic cancer. In general, resection of
adjacent organs, most commonly the stomach or left hemicolon in left resections and the right hemicolon in Whipple procedures as well as either adrenal gland or kidney in both types
of resection can be performed safely to achieve a R0 situation.
Technically, an en bloc resection should be performed without
preparation along or injuring the tumor surface. This may
result in typical resections such as right or left colectomies as
well as individual segmental- or wedge-type resections. Multivisceral approaches can also be combined with vessel resections of the portal vein or the celiac axis. From the limited
number of available studies, this approach is associated with
an increased intraoperative blood loss and overall surgical
morbidity as well as ICU and hospital stay (58,60). However,
there seems to be a survival advantage in these patients and
overall mortality is not increased compared to standard resections (59,60). Due to the limited number of patients reported
so far, it is not possible to give valid data on long-term

oncological outcome, making multivisceral resections an individually tailored approach that requires careful patient selection and surgical experience.
Recurrence Resections
Localized recurrence in pancreatic cancer may be an indication for relaparotomy and resection in selected patients.
Although a large number of recurrences are located close to
the arterial vessels, and therefore not resectable, recent studies
support the concept of surgical exploration and resection
whenever possible (6163). This approach can be combined
with intraoperative radiotherapy and radiation of the tumor
bed to reduce the risk of another recurrence at the site of resection (Fig. 8.8). In case of local irresectability, intraoperative
radiation can be performed with a palliative intention in terms
of tumor reduction and pain control. An extended resection of
the recurrent tumor with arterial vessels does not seem to be
justified as the chance for a radical tumor removal is poor and
patients do not seem to benefit from R1 or R2 resections. The
available studies report successful resection rates of approximately 50% with acceptable surgical morbidity and suggest a
survival benefit for those patients, especially in situations with
a long time interval (>912 months) between the initial tumor
diagnosis and the recurrence manifestation (63). As these are
observational studies, there is no proven evidence for this
approach today and larger controlled trials are required to
evaluate long-term oncological value.
Metastasis Resections
Resection for metastatic pancreatic cancer is clearly restricted
to exceptional indication and has only been reported anecdotally so far (64,65). Most commonly, the indication for metastasis resection arises in young patients with the accidental
finding of a synchronous single liver lesion intraoperatively,
which can be removed without increasing operative
morbidity (64). Apart from this individual indication, metastasis resection can be performed in long-term survivors with

Figure 8.8 Pancreatic cancer recurrence resection. Intraoperative finding of the recurrence located in the interaortocaval space (left), situs after resection (right)
prior to intraoperative radiation.

78

PANCREATIC RESECTION
localized metastastic disease, indicating favorable tumor biology and justifying the aggressive operative approach. This has
to be embedded in a global oncological concept, must be
decided highly individually and cannot be regarded as a
standard procedure (65).

conclusion
Pancreatic surgery has undergone a remarkable development
during the last decades. Appropriate surgical approaches have
been established and can be used in differential indications
today. In pancreatic cancer, standard resections include the
classical Whipple operation and the pylorus-preserving modification, which should be preferred whenever possible as well
as a distal or total pancreatectomy in extended tumors of the
gland. All of these procedures can be carried out safely with
surgical mortality rates well below 5% in specialized centers
due to a high grade of standardization and experience. Modern
tissue-sparing procedures such as the duodenum-preserving
pancreatic head resection in chronic pancreatitis or tumor
enucleations offer limited approaches for circumscribed nonmalignant pancreatic pathologies. Furthermore, extended
resections for the treatment of pancreatic malignancies
including multivisceral and recurrence resectionsare technically feasible although the oncological outcome of these
procedures has to be further evaluated and pancreatic cancer
treatment must always be embedded in an interdisciplinary
concept of surgery and adjuvant therapy to ensure best
possible outcome.

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Surgical complications of pancreatectomy


Steven C. Katz and Murray F. Brennan

Pancreatic resection and the associated complications remain


challenging problems for patients and surgeons. Since the earliest reports describing the technique of pancreaticoduodenectomy (PD) by Kausch and Whipple, significant reductions
in operative mortality and morbidity have been achieved (1,2).
Postoperative mortality rates have been reduced from greater
than 25% in the 1960s to less than 5% in specialized centers (3).
The lower risk of death following pancreatic resection is due
to advances in operative technique, improvements in perioperative care, percutaneous and endoscopic management
of complications, and refinements in patient selection (4).
Unfortunately, morbidity rates for PD continue to exceed 30%
to 40% in large series (59).
We discuss the prevalence, nature, predisposing factors, and
management for major surgical complications that occur following pancreatic resection. While there are many nonsurgical
complications that occur following pancreatic resection, these
are not addressed. Right, left, central, and total pancreatectomies are discussed separately where appropriate. The most
common individual complications are considered, followed by
factors affecting morbidity rates. Throughout, we outline
operative strategies and postoperative interventions that
impact the risk and severity of surgical complications following pancreatectomy.

specific complications
Pancreatic Anastomotic Leak and Pancreatic Fistula
Pancreatic leak occurs in 7% to 29% of patients following pancreatic resection (Tables 9.1 and 9.2) (5,7,1014). The wide
range in incidence is due in part to variability in defining the
manifestations of pancreatic leaks and several classification
systems have been proposed (9,15,16). Given similarity in
management and clinical manifestations, pancreatic leak,
fistula, fluid collection, and abscess will be considered
together (12).
Parenchymal consistency and the extent of operation are
associated with pancreatic leak following right or left pancreatectomy (Table 9.3) (17). Small pancreatic duct diameter is a
predictor of leak following PD (7,18). Management of fluid
collections resulting from a pancreatic leak may involve operative drains, placement of postoperative drains, or reoperation
(Fig. 9.1). Vin et al. reported that prolonged drainage was predicted by volume collected during the first 48 hours, fluid
amylase >1000, or distal pancreatectomy (12). The magnitude
of the pancreatic leak may also depend on whether the source
is the main duct or parenchyma (19). Those patients who do
develop pancreatic leaks are more likely to suffer from other
complications or death, and this risk is exacerbated by superimposed infection (12). Numerous strategies have been
attempted to minimize the chances of pancreatic leakage and
these are discussed below.

Delayed Gastric Emptying


The incidence of delayed gastric emptying (DGE) following
PD ranges from 4% to 29% (5,11,13) and is associated with
other intraabdominal complications (Table 9.1). While DGE is
not associated with an increased risk of death, it does prolong
hospitalization time (5,20). Parameters used to define DGE
include the volume of nasogastric tube output, the length of
time before tolerance of oral feeding, and results of scintigraphic studies. At our institution, DGE is defined as failure to
achieve oral intake sufficient to maintain adequate hydration
by postoperative day 10 (9).
DGE is thought to be due to numerous factors, including
management of the pylorus, extent of retroperitoneal dissection, intraabdominal fluid collections, and decreased motilin
activity (21). Early reports indicated that pylorus-preserving
pancreaticoduodenectomy (PPPD) increased the risk of DGE
(22,23) but subsequent studies have failed to confirm this
(Table 9.4) (24,25). Radical resection or extended retroperitoneal dissection may also be associated with DGE (26). It is
unclear if more extensive dissection has a direct effect or if
higher rates of pancreatic leak, sepsis, or hemorrhage predispose to DGE (25). Expeditious management of fluid collections, infection, or bleeding may limit gastric dysmotility.
An additional contributing factor to DGE may be reduced
levels of circulating motilin following PD (27). In a randomized control trial (RCT) including 118 patients undergoing
PD, erythromycin, the motilin analogue, reduced the DGE rate
from 30% to 19% compared to placebo (21). By contrast, routine nasogastric decompression or withholding of oral feeding
has not been shown to affect the rate of DGE. Based upon data
from RCTs involving patients subjected to gastrectomy, routine nasogastric tube placement following pancreatic surgery
is unnecessary (28,29). Furthermore, early oral feeding should
be considered following major abdominal procedures (30,31).
Postpancreatectomy Hemorrhage
Postpancreatectomy hemorrhage (PPH) occurs in 2% to 9%
of cases and the consequences may be severe (8,3237). The
initial evidence of hemorrhage may be the sentinel bleed,
which is present in 30% to 100% of patients prior to massive
PPH (3841). Risk of PPH is related to inadequate intraoperative hemostasis, bile leak, pancreatic leak, intraabdominal
infection, and sepsis (39,40,4244). The presence of jaundice
at the time of pancreatic resection may increase the risk of
PPH, but this is not lessened by preoperative biliary
drainage (37). The implications and management of PPH vary
depending on the time of onset and source (4).
Postoperative bleeding within the first 24 hours is most
often due to a technical failure and requires reoperation if
severe (35). The most appropriate course of action for PPH
occurring beyond the immediate postoperative period will

81

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Table 9.1 Complications Following Pancreaticoduodenectomy
Author
Balladur (42)
Bottger (10)
Gouma (11)
Balcom (5)
Muscari (7)
Winter (13)
Vin (12)
House (49)
Baker (47)

Pancreatic
Fistula or Leak

Delayed Gastric
Emptying

Hemorrhage

Bile Leak

Overall
Complications

223
228
300
489
300
1423
680
356
440

13%
8%
7%
13%
17%
9%
18%
15%
16%

NR
NR
29%
12%
NR
15%
NR
4%
7%

9%
NR
5%
NR
6%
NR
NR
NR
2%

NR
<1%
2%
2%
<1%
2%
NR
NR
2%

41%
26%
48%
39%
39%
38%
NR
38%
36%

Death
9%
6.1%
10.1%
11%
2%
2.0%*
1.7%
1.6%

*Includes pancreaticoduodenectomy, central pancreatectomy, and distal pancreatectomy.

Table 9.2 Complications Following Distal Pancreatectomy


Author
Bottger (10)
Balcom (5)
Pannegeon (103)
Siergaza (104)
Ridolfini (105)
Kleeff (50)
Ferrone (14)
Vin (12)

Fistula or Leak

Hemorrhage

Overall Complications

72
190
175
132
64
302
462
220

13%
13%
23%
14%
22%
12%
29%
13%

NR
NR
2%
4%
3%
3%
NR
NR

27%
26%
42%
57%
37%
35%
NR
NR

Death
1.7%
1.5%
0
5.0%
1.5%
2.0%
0.8%
2.0%*

*Includes pancreaticoduodenectomy, central pancreatectomy, and distal pancreatectomy.

Table 9.3 Predictors of Pancreatic Leak or Fistula


Following Pancreaticoduodenectomy
Small duct diameter (7,10)
Friable parenchyma (7,10)
Extended resection (7)
Placement of intraoperative drains (59)
Blood loss (10)
Obesity (49)
Following Distal Pancreatectomy
Multivisceral resection (14,104,105)
Proximal (body) transaction (103)
Friable parenchyma (105)
Malnutrition (104)
Obesity (14)

depend on its location. Extraluminal PPH may arise from the


gastroduodenal artery (GDA), splenic artery, or tributaries of
the superior mesenteric vessels. Intraperitoneal hemorrhage
is often associated with a pancreatic leak and options include
reoperation or angioembolization. When reoperation is
selected, completion pancreatectomy and suture ligation of
the bleeding vessel have been advocated (45). Operative
intervention more than 1 week following pancreatic resection may be particularly challenging due to adhesions and
tissue friability (46). Arterial embolization is valuable under
these circumstances, with a success rate of approximately
80% (Fig. 9.2) (41). We advocate distal ligation of the GDA to

82

ensure the technical feasibility of angioembolization as it


may not be possible when the bleeding point is in close proximity to the common hepatic or superior mesenteric artery.
Intraluminal PPH should be initially addressed endoscopically and may originate from anastomoses, mucosal ulceration, or the cut pancreatic surface. When bleeding is found
to originate from the cut pancreatic surface, hemostasis may
be achieved during reoperation through a jejunotomy or gastrotomy (32).
In summary, PPH may occur in up to 9% of patients. The
timing and location of the bleeding in patients suffering from
PPH are important factors in predicting outcome and determining appropriate management. The overall mortality of
PPH is as high as 16% and delayed PPH is associated with a
47% chance of death (41,43). Appreciation of the clinical
factors associated with PPH, including sentinel bleeding, sepsis, and pancreatic leak, facilitates prompt recognition.
Bile Leak
The incidence of choledochoenteric leak following PD is
notably lower than pancreatic leak or fistula (Table 9.1). The
larger size of the bile duct and more reliable tissue integrity
may account for the relative infrequency of biliary leak when
compared to pancreatic leak. Similar to pancreatic leak, bile
leak is associated with both sterile and infected intraabdominal fluid collections (47). The vast majority of biliary leaks or
fistulae can be managed by percutaneous, transhepatic, or
transabdominal drainage (48).

SURGICAL COMPLICATIONS OF PANCREATECTOMY


Table 9.4 Pylorus Preservation
DGE %

Morbidity %

Mortality %

LOS (days)

OR TIME
(minutes)

EBL

Author

PD

PPPD

PD

PPPD

PD

PPPD

PD

PPPD

PD

PPPD

PD

PPPD

Van Berge
Henegouwen (25)

200

34

37

48

44

20

18*

1580

1247*

360

288*

Lin (23)

31

38

50

56

687

451

237

215

Jimenez (106)

62

12

33

45

44

12

15*

723

707

114

45

32

72

57*

24

25

2096

1453*

476

404*

Seiler (24)

*p < 0.05, DGE = delayed gastric emptying, PD = standard pancreaticoduodenectomy, PPPD = pylorus-preserving pancreaticoduodenectomy,
LOS = length of stay, EBL = estimated blood loss.

Figure 9.1 The patient presented with fever and abdominal pain 2 weeks after a pancreaticoduodenectomy. A CT scan revealed a fluid collection in the RUQ (long
arrow), which was managed with CT-guided percutaneous drainage (catheter indicated by short arrow). The amylase level in the aspirated fluid was consistent with
a pancreatic leak (11,320 U/L).

Death
Long-term survival following pancreatic resection is a function of the underlying disease, while perioperative mortality is
related to the occurrence of complications, in addition to
patient, institutional, and technical factors. Fortunately, the
perioperative mortality rate following pancreatic resection has
been reported to be less than 2% in the most recent large series
(1214,47,49,50). Pancreatic leak (11) and PPH (40,51,52) are
the complications most frequently associated with perioperative mortality. As noted above, the improved mortality rates
following pancreatic resection are due in large part to better
management of complications. The vast majority of complications can be managed percutaneously, thereby reducing their
severity and the risk of death (47).

factors affecting complication rates


following pancreatectomy
Pancreatic Duct Management Following Resection
Pancreatic leaks prolong hospitalization, and are associated with
other complications including DGE, intraabdominal abscess,
and cholangitis (3,53). Numerous strategies for management of
the pancreatic duct following PD have been advocated, including pancreaticojejunostomy (PJ), pancreaticogastrostomy (PG),
and duct ligation (DL). In addition, several technical modifications to distal pancreatectomy (DP) have been tested to
reduce the leak rate.

Figure 9.2 Following a pancreaticoduodenectomy and hemodynamic instability, metallic coils were placed in the gastroduodenal artery stump (long
arrow) to treat a suspected pseudoaneurysm. The catheter is positioned within
the common hepatic artery (short arrow).

Investigators at Johns Hopkins compared PG and PJ in


145 patients who underwent PD and found that the two
methods were associated with similar leak rates (53). Several

83

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


variations of PJ have been reported including invagination,
end-to-side anastomosis, and side-to-side anastomosis. When
compared to end-to-side (duct to mucosa) PJ, end-to end
(invaginating) PJ was associated with a trend toward a higher
pancreatic fistula rate (15% vs. 4%, p > 0.05). (54) Pancreatic
duct ligation following PD as opposed to PG or PJ posed a
greater risk of adverse outcomes (55). Marcus et al. also
reported that duct ligation following PD was an independent
risk factor for pancreatic leakage (18). Whether PG or PJ is
employed, ensuring robust perfusion to the cut pancreatic
surface prior to anastomosis is essential (56).
Various techniques have been applied to both right and left
pancreatic resections. Suc et al. (57) conducted an RCT with
182 patients undergoing DP or PD and determined that the
use of fibrin glue did not affect the overall complication rate or
incidence of pancreatic fistula. Thaker et al. reported that the
use of absorbable mesh with a stapler reduced the leak rate
significantly among 40 patients undergoing DP compared to
the 40 control cases (58). Ferrone et al. did not confirm the
efficacy of reinforcing pancreatic transection margins (14).
Peritoneal Drainage
The only randomized trial addressing the value of routine
intraperitoneal drainage following pancreatic resection did
not show a benefit (59). Patients who underwent pancreatic
resection at the Memorial Sloan-Kettering Cancer Center were
randomized to placement of closed suction drains (n = 88) or
to no drain placement (n = 91). Those patients who had drains
placed were significantly more likely to develop intraperitoneal sepsis, fluid collections, or fistulae (22% vs. 9%, p < 0.02).
Thus, placement of drains following pancreatic resection
should be considered on a selective basis.
Octreotide
The pathogenesis of pancreatic leaks has been thought to
involve the enzymatic activity of the exocrine secretions. Thus,
investigators have tested the ability of octreotide, a synthetic
somatostatin analogue, to reduce the risk of postpancreatectomy complications (Table 9.5) (60). The majority of trials
demonstrated that octreotide was associated with a significant
reduction in perioperative morbidity (6164). Two trials
showed a significant reduction in the incidence of pancreatic
fistula in patients receiving octreotide (62,63). The overall frequency of pancreatic fistula was particularly low in two of the
trials in which octreotide and placebo were similar (65,66).

The trials differ with respect to the proportion of patients


undergoing right or left pancreatic resection, frequencies of
various diagnoses, the dose of octreotide, and the definitions
of pancreatic leak. Given the discrepant results among available trials, the routine use of octreotide for the prevention of
pancreatic fistulas cannot be recommended. Individuals at
high risk for pancreatic leak (61), such as those with ampullary
cancer or soft, friable glands may benefit from exocrine
inhibition. The cost of the drug must be balanced against its
impact on length of stay and potential avoidance of additional
procedures.
Pylorus-Preserving Pancreaticoduodenectomy
In a RCT comparing classic PD and pylorus-preserving PD
(PPPD), the incidence of pancreatic fistula was not significantly different but PPPD was associated with more instances
of DGE (23). This study was limited by small sample size and
the difference in incidence of DGE between the two groups
was not statistically significant. A subsequent RCT demonstrated that cumulative morbidity was significantly more frequent following classic PD when compared to PPPD (72% vs.
57%, p = 0.05) (24). Other trials failed to show significant differences in the rates of DGE or overall surgical complications
when comparing classic PD to PPPD (Table 9.4). The decision
to perform a PPPD or classic PD is a matter of surgeon preference as the two procedures do not result in markedly different
perioperative outcomes.
Extended Lymphadenectomy and Resection
of Contiguous Structures
Several investigators have studied the impact of extended
retroperitoneal lymphadenectomy in patients with adenocarcinoma of the pancreas. In a multicenter prospective
randomized trial involving 81 patients, extended lymphadenectomy did not significantly affect operative time, blood
loss, morbidity, or mortality when compared to the standard
dissection (67). The number of lymph nodes removed was
similar among the two groups and the extent of resection
did not correlate with locoregional control. Yeo et al.
reported that radical PD increased operative times (68), as
well as the rates of pancreatic fistula, delayed gastric emptying, and overall morbidity (26). Radical or extended PD
does not appear to confer an oncologic benefit in patients
with adenocarcinoma and may be associated with higher
morbidity rates.

Table 9.5 Prophylactic Octreotide


Pancreatic Fistula %
Author
Buchler (61)
Pederzoli (64)
Montorsi (63)
Friess (62)
Lowy (65)
Yeo (66)

Mortality %

Placebo

Octreotide

Placebo

Octreotide

Placebo

Octreotide

246
252
218
247
110
211

38
19
20
22
6
11

18^
9
9*
10*
12
9

55
29
36
30
25
34

32*
16*
22*
16*
30
40

5.8
3.8
5.6
0.8
0
0

3.2
1.6
8.1
1.6
2
1

*p < 0.05 versus the control group, ^statistical significance not indicated.

84

Morbidity %

SURGICAL COMPLICATIONS OF PANCREATECTOMY


Among the 10% to 20% of patients with adenocarcinoma of
the pancreas who are potentially curable, resection of contiguous structures, including the portal vein or spleen, may be necessary in up to 39% (69). While those undergoing resection of
contiguous structures may experience higher degrees of intraoperative blood loss and longer hospital stays, perioperative
and long-term outcomes are not significantly different (70).
When portal vein involvement is the only factor precluding a
potentially curative pancreatectomy, resection of the vessel
with appropriate reconstruction may be performed without a
significant change in operative mortality (71). In a separate
study, splenectomy did not lead to increased perioperative
morbidity but was associated with decreased survival in
patients with pancreatic adenocarcinoma (72). Whether these
findings are the result of direct immunologic effects of splenectomy or reflections of more aggressive tumor biology
remains uncertain.
Total and Central Pancreatectomy
The incidence of multifocal pancreas adenocarcinoma is sufficiently low to render total pancreatectomy (TP) unnecessary
in the vast majority of cases (73,74). The perioperative (75)
and long-term outcomes (76) following TP for adenocarcinoma are even less favorable than those obtained following
partial pancreatectomy. The lack of an incremental benefit of
TP, along with the endocrine and exocrine sequelae, has limited the use of TP (77). However, increased recognition of
intraductal papillary mucinous neoplasms (IPMNs) has led to
increased interest in TP (78). Quality of life following TP may
not be significantly different from patients with diabetes mellitus not undergoing pancreatic resection (79). Intermittent
hypoglycemia is the most common endocrine complication,
but fewer than 3% die following TP due to metabolic derangements (80,81). Although islet cell transplantation may delay or
prevent the diabetic complications of total pancreatectomy,
the role of the procedure is not fully defined (82).
As the use of cross-sectional imaging has increased, the frequency of cystic and neuroendocrine lesions of the pancreas is
growing. Given that cystic and neuroendocrine pancreatic
tumors are often noninvasive, parenchyma-sparing pancreatic
resections, such as central pancreatectomy (CP), may be
appropriate (83). CP may pose a lower risk of diabetes mellitus
than extended DP (84,85) and the rate of exocrine insufficiency is reported to be between 0% and 20% (8487). The
range of pancreatic fistula formation following CP is 1462%
(8388), which is somewhat higher than what has been associated with right or left pancreatic resection. However, in a
recent series, the overall rate of major complications was
similar following CP when compared to extended DP (84).
Laparoscopic Pancreatectomy
Since initially reported (89), laparoscopic distal pancreatectomy is being performed with increasing frequency due to
growing interest among patients and physicians. There are no
RCTs from which to draw definitive conclusions about complications. Two series including a total of 286 laparoscopic left
pancreatectomies indicate a pancreatic fistula rate of 16%
to 17% (90,91). The oncologic equivalence of laparoscopic

pancreatic resection to conventional approaches remains to be


proven. One advantage of laparoscopic pancreatectomy appears
to be a decreased length of stay (90). Laparoscopic right and
central pancreatectomies are not widely performed and the literature is limited to case reports and small series. In properly
selected patients, laparoscopic pancreatectomy may offer shortterm benefits when performed by experienced surgeons.
Institutional Factors
Hospital or surgeon volume and practice paradigms influence
outcome and cost following pancreatic resection. Short-term
mortality rates following PD are lower in high-volume compared to low-volume centers (92,93). Improved outcomes in
high-volume centers are more likely a reflection of systematic
factors rather than an independent effect of more experienced
surgeons (93). Utilization of clinical pathways following pancreatic resection has been demonstrated to lower overall cost
and decrease the average length of stay by 3 to 6 days (94,95).
Clinical pathways have not been associated with significant
reductions in morbidity or mortality in patients undergoing
pancreatic resection (96).
Patient Factors
Numerous patient-related factors have been purported to
increase the risks of complications and death following pancreatic resection. As noted elsewhere in this chapter, large duct
diameter and firm pancreatic parenchymal texture may be
associated with a lower risk of pancreatic leak (Table 9.3).
Other patient variables that have been reported to increase
morbidity rates include coagulopathy, severe jaundice, acute
renal failure, obesity, and protein-calorie malnutrition
(9799). Age has not been shown to be an independent risk
factor for morbidity and mortality following pancreatectomy
(10). The impact of morbid obesity on the risk for postpancreatectomy complications deserves special attention given the
scope of this problem in the U.S. population. House et al.
determined that retrorenal visceral fat thickness was an independent predictor of overall morbidity, wound infection, and
pancreatic fistula (49).
Whether jaundice increases the risks of pancreatic resection
and the impact of preoperative biliary drainage on perioperative outcomes remain an area of considerable controversy.
Povoski et al. (100) demonstrated that in patients undergoing
PD, preoperative biliary drainage was an independent predictor of postoperative infection, overall complications, and
death. In contrast, Pisters et al. (101) reviewed their experience with preoperative biliary decompression in patients subjected to PD and determined that drainage did not increase
the overall morbidity or mortality rates, but did increase the
rate of wound infections. A recent meta-analysis of RCTs and
comparative cohort studies concluded that there is no benefit
to routine preoperative biliary drainage (102). Routine preoperative biliary drainage in jaundiced patients with pancreatic head tumors does not appear to be warranted, but may
be appropriate in properly selected patients. Biliary decompression should be considered to address acute cholangitis,
intractable pruritis, or to facilitate participation in studies
investigating neoadjuvant therapy.

85

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


Table 9.6 Recommendations for Prevention or Management of Pancreatectomy Complications

Radical pancreatectomy or extended retroperitoneal lymphadenectomy may be associated


with a higher rate of certain complications and does not confer a significant benefit in
oncologic outcome.
Restoration of pancreaticoenteric continuity as opposed to ductal ligation is associated
with significantly lower rates of pancreatic fistula and endocrine insufficiency.
Pancreaticojejunostomy and pancreatogastrostomy following PD have similar
complication rates.
Pylorus preservation and PD with distal gastrectomy lead to similar perioperative
outcomes.
Utilization of absorbable mesh when transecting the distal pancreas with a stapling device
has not been definitively shown to decrease the risk of pancreatic leak.
Routine use of octreotide following pancreatic resection is not indicated but may be useful
in selected, high-risk patients.
Routine preoperative biliary drainage prior to pancreaticoduodenectomy is not indicated
and should be performed in selected patients based upon the presence of symptoms,
infection, or severe hyperbilirubinemia.

Evidence Category

Recommendation
Strength Category

Ib

Ib

Ib

Ib

III

Ib

Ia

Recommended grading of categories of evidence: Ia, evidence from meta-analysis of randomised controlled trials; Ib, evidence from at least one randomised
controlled trial; IIa, evidence from at least one controlled study without randomisation; IIb, evidence from at least one other type of quasi-experimental study;
III, evidence from nonexperimental descriptive studies, such as comparative studies, correlation studies and case-control studies; IV, evidence from expert
committee reports or opinions and/or clinical experience of respected authorities. Recommended strengths of management recommendation: A, directly based
on category I evidence; B, directly based on category II evidence or extrapolated recommendation from category I evidence; C, directly based on category III
evidence or extrapolated recommendation from category I or II evidence; D, directly based on category IV evidence or extrapolated recommendation from
category I, II, or III evidence.

summary
While the mortality rates following pancreatic resection
have improved dramatically, the incidence of complications remains high. Based upon the available literature,
several recommendations have been proposed ( Table 9.6).
Refinements in our abilities to detect and manage complications following pancreatectomy account, in large part,
for improved perioperative mortality statistics. Further
progress in enhancing the safety of pancreatic resection
will depend upon the development of more effective measures to prevent and treat postpancreatectomy complications. Better understanding of the biology of the diseases
we subject to pancreatic resection will allow for more precise patient selection and improve both perioperative and
long-term outcomes.

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85. Adham M, Giunippero A, Hervieu V, et al. Central pancreatectomy:


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in the treatment of chronic pancreatitis. Ann Surg 2000; 231(3): 293300.

10

Laparoscopy in HPB surgery


Nicholas ORourke and Richard Bryant

introduction
Laparoscopy offers great advantages to the patient with HPB
disease. Although described in the early part of the 20th century, crude instrumentation limited its use. Progress seemed
slow until the 1960s saw widespread uptake in the gynecologic
community, with the Hopkins rod lens system greatly improving the optics.
Sporadic reports of laparoscopic staging for HPB cancer
soon followed, but it was not until the handheld camera development in the 1980s that the minimal access explosion began.
Now surgeons could view the image on a monitor, and use two
hands to operate instruments, while an assistant held the camera. Even the gall bladder could be removed using tiny incisions. The next 10 years saw almost every abdominal operation
attempted, such that the interest now is not in what can be
done, but in what should be done, and how best to do it.

laparoscopic cholecystectomy
Cholecystectomy was the first general surgical procedure to be
widely performed laparoscopically. Following the first reports
in 1985 and 1988 (1), the technique was rapidly popularized
(25). Despite a possible increase in the incidence of severe
bile duct injuries, the benefits of the laparoscopic approach
have subsequently been confirmed by meta-analysis (6), demonstrating shorter hospital stay and faster convalescence with
no difference in operating time or complications.
There are various techniques in common usage, with the
surgeon standing either on the patients right or left or between
the legs, with the choice of technique depending on local
teaching and personal preference. There are, however, fundamental principles to safely performing a laparoscopic cholecystectomy.
Correct identification of the anatomy is fundamental. Most
bile duct injuries are due to misperception rather than technical errors (7). It is important to understand the normal variations in biliary anatomy and how pathological changes may
alter the relationships between the structures. The 30 telescope permits better visualization of Calots triangle.
Hartmanns pouch is retracted laterally and inferiorly so that
the angle between the cystic and common hepatic ducts is
increased rather than closed. Calots triangle is dissected high,
just beneath the edge of the gall bladder, on both its anterior
and posterior surfaces, to clearly identify the cystic duct and
cystic artery as the only structures passing to the gall bladder
(the critical view (8)). Dissection is never carried below the
plane of Rouvires sulcus (9).
Routine intraoperative cholangiography is recommended.
This has been shown to decrease the risk and severity of biliary
injury (10). It is essential that the full complement of upper
duct anatomy is visualized to be certain that the common bile
duct or an aberrant right hepatic duct is not being excised. It

also enables the identification of choledocholithiasis, which in


most cases can then be successfully managed during the same
laparoscopic procedure (11).
In the setting of acute cholecystitis, early laparoscopic cholecystectomy is preferred (12,13). The problem with a policy of
delayed laparoscopic cholecystectomy is that a significant proportion of patients require an emergency cholecystectomy for
recurrent or nonresolving acute cholecystitis in the difficult
intermediate period with a higher rate of conversion. However, if symptoms have been present for more than a week or
there is a mass present without generalized peritonism then it
may be more prudent to manage the patient conservatively
with a view to a delayed cholecystectomy.
For mild gall stone pancreatitis, laparoscopic cholecystectomy with intraoperative cholangiogram should be performed
during the same admission (14). A policy of interval cholecystectomy incurs a real risk of recurrent pancreatitis (1521).
Laparoscopic cholecystectomy has traditionally been performed with an overnight stay, but appropriately selected
patients can be safely managed as a day case (22).

laparoscopic common bile duct exploration


Most common duct stones can be managed laparoscopically
(11,2336). This allows treatment in one operation, rather
than endoscopic retrograde cholangiopancreatography
(ERCP) and sphincterotomy done as a separate procedure,
either before or after laparoscopic cholecystectomy. Obviously,
operative cholangiography, with fluoroscopy, and accurate
interpretation is mandatory. Techniques used, in order of
increasing complexity, are as follows:

Transcystic flushing
Transcystic stone extraction
Choledochotomy
Transampullary stenting
Choledochoduodenostomy

Flushing
Small filling defects in the bile duct may be air bubbles, and
only the dynamic image of fluoroscopy may allow visible distortion or coalescence of these bubbles. Small stones low in the
bile duct may be flushed or pushed into the duodenum using
the cholangiogram catheter, with intravenous glucagon occasionally helping by relaxing the sphincter.
Transcystic Stone Extraction
Formal duct exploration is performed, where possible (in
about two-thirds of cases), via a transcystic approach. We prefer to use a purpose-built Nathanson CBD exploration catheter (Cook). This allows manipulation of a basket under
contrast-assisted fluoroscopy. The cystic duct is dissected
lower, close to the common bile duct. Balloon dilatation of the

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


cystic duct may occasionally be required. The stone to be
extracted must not be larger than this diameter. If so, the stone
may become stuck in the junction and require fragmentation
or, worse, incision to remove. Choledochotomy as a primary
procedure may be preferred for large or numerous stones.
When inserting the Nathanson transcystic catheter, one
must be careful that the basket is 1 to 2 cm inside the flexible
tip of the catheter, to avoid turning the device into a spear,
which can perforate the posterior aspect of the common duct.
Under fluoroscopic guidance, the wire basket is deployed in
the distal common bile duct, without traversing the ampulla.
Gentle jiggling of the basket entraps the stone, which can
then be retrieved by withdrawing the open basket. The stone
can flip out of the duct and land anywhere in the right abdomen, often too quickly to be seen (Figs. 10.1 and 10.2). The
characteristics of the basket employed are important. A fourwire steel basket will spring open in the bile duct such that
with jiggling the stone is able to enter between the wires to
then be trapped in the apex as the open basket is withdrawn. A
softer nitonol basket will not tend to spring open in the same
fashion and it is therefore often difficult to ensnare the stone
under fluoroscopic guidance.
An alternative transcystic approach is with a flexible choledochoscope. A 3-mm scope is normally required, as a 5-mm
scope will only rarely pass trans-cystically. A grasper in the epigastric port provides traction to the right. A long 5-mm trocar
in the right subcostal position is positioned against the cystic
duct incision to prevent bowing of the choledochoscope
within the abdomen. The choledochoscope is advanced into
the common bile duct and the stone retrieved under direct
vision. In these circumstances, a nitonol basket with a parachute arrangement at the apex is usually more effective as the
stone entrapment is performed under direct vision. Clearance
of the common bile duct can be confirmed by transcystic flexible choledochoscopy; however it is often difficult transcystically to introduce the choledochoscope to the common hepatic
duct to confirm that there are no calculi above the cystic
duct junction.

If the transcystic approach fails, then a decision must be


made between postoperative ERCP versus laparoscopic choledochotomy. A randomized controlled trial between these
two options, after failure of transycstic CBDE, did not demonstrate any differences (27), and therefore the choice depends
on individual patient factors and local expertise. If the common bile duct is narrow (<7 mm) then a choledochotomy
should be avoided due to the risk of stricturing. Postoperative
ERCP can be facilitated by the passage of an antegrade biliary
stent (37).

Figure 10.1 Laparoscopic transcystic cholangiography demonstrating calculus in the distal common bile duct.

Figure 10.2 The calculus from Figure 10.1 after transcystic extraction utilizing
the Nathanson basket. Inset: completion cholangiography.

90

Choledochotomy
In certain circumstances, a transcystic approach is unlikely to
be successful, and if the CBD is of sufficient diameter, then it is
reasonable to proceed straight to a laparoscopic choledochotomy. These circumstances include large stones (>10mm),
multiple stones (>3) or stones above the cystic duct
confluence.
To perform laparoscopic choledochotomy, the anterior surface of the common bile duct is dissected just sufficiently to
confidently identify the anatomy. A 1.5-cm vertical incision is
made in the common bile duct below the cystic duct confluence. Filling of the duct system with saline via the transcystic
catheter distends the collapsed duct and helps prevent injury
to the posterior duct wall when the anterior wall is incised.
Another method is to gently lift up the anterior wall with a
suitable small atraumatic grasper (such as a dolphin-nose)
introduced via the right subcostal port. This will create a small
transverse ridge of the anterior duct wall, which can then be
cut using scissors introduced via the epigastric port, thus creating a vertical incision that can then be extended with the
scissors. A similar effect can also be created using stay sutures.
Initial flushing via the choledochotomy with the suckeraspirator and massaging of the duct may remove the stones. A
choledochoscope can be introduced, this time from the epigastric port. A 3 or 5 mm flexible scope may be employed, or
even a rigid ureteroscope if the orientation is suitable. (On the
rare occasions that a rigid ureteroscope is required, it can

LAPAROSCOPY IN HPB SURGERY


sometimes be introduced transcystically via the epigastric port
if the orientation is suitable.) With the choledochoscope, the
stones can be removed under direct vision, and the flexible
choledochoscope can be maneuvered into both the upper
ducts and lower CBD to confirm clearance of all calculi. On
rare occasions, hydraulic lithotripsy may be required to break
up impacted stones (27).
Where there is confidence about stone clearance and biliary
drainage, choledochotomy can be simply closed by
suturing (25). If there is any doubt about biliary drainage or
duct clearance, then choledochotomy should be closed after
passage of an antegrade biliary stent, or a T-tube inserted.
Choledochoduodenostomy
For the elderly patient with a suspected benign stricture, and a
reasonable stone load, laparoscopic choledochoduodenostomy
is a good option (23). As in open surgery, a common duct
diameter of greater than 10 mm is preferable. A continuous
absorbable suture is used, and the operation mimics the open
procedure with anastamosis of the choledochotomy to a longitudinal opening in the duodenum.

pancreatic pseudocyst
Pancreatic pseudocysts can be managed endoscopically with
gastrotomy and stenting (perhaps the only current valid indication for NOTES [Natural Orifice Transabdominal Endoscopic Surgery]). Pancreatic pseudocysts can also be drained
internally via a laparoscopic approach (3846). Most commonly the pseudocyst is located in the lesser sac and the appropriate procedure is a cyst-gastrostomy. An anterior gastrotomy
is made. The cyst can be seen bulging forward, adherent to the
posterior stomach wall, which is incised with diathermy or the
harmonic scalpel to enter the cyst. Cyst fluid will come flowing
out under pressure at this point, and is important to have an
instrument ready to pass into the cyst so that the point of
communication is not lost. The cyst fluid is aspirated with the
sucker and the cyst emptied. A linear stapler is then introduced into the small cyst-gastrotomy to create a wide cystgastrostomy, and the residual unstapled edges are sutured
together. The pseudocyst can be entered with the laparoscope
and inspected, and any debris removed. The anterior gastrotomy is then closed with sutures or a stapling device. In some
cases, the position of the pseudocyst will require a side-to-side
cyst-gastrostomy or Roux-en-Y cyst-enterostomy.
Published reports suggest that laparoscopic cyst-gastrostomy
has a higher initial success rate and lower recurrence rate than
endoscopic cyst-gastrostomy (42,47). As the cyst-gastrostomy
created via the endoscopic approach is only small, any large
debris is unable to exit the cyst. However, endoscopic
approaches can be improved with using balloon dilatation and
multiple stents to maintain better drainage, endoscopic ultrasound to guide the procedure and avoid vessels (48,49), and
with the development of stapling instrumentation for natural
orifice surgery (50).

imaging studies, but be found to have locally advanced disease


or small liver or peritoneal metastases (imaging-occult metastases) that render the disease inoperable (Fig. 10.3). Staging
laparoscopy can identify these patients and therefore spare the
patient a laparotomy. Staging laparoscopy in its simplest form
involves visual inspection of the peritoneal and liver surfaces,
but may also include laparoscopic ultrasound, trial dissection,
or peritoneal washing for cytology.
Staging laparoscopy is preferable to a nontherapeutic laparotomy to identify unresectability. The hospital stay is shorter
(51,52), and the patient is able to start chemotherapy
sooner (53). The risks of a staging laparoscopy are low, with
morbidity reported at 0% to 4% and mortality 0% to
0.15% (54). Port-site recurrences are uncommon, between 0%
and 2% (54), and usually occur in patients with extensive peritoneal carcinomatosis. Staging laparoscopy may be performed
as a prelude to resection in the same procedure or as a separate
procedure prior to planned resectionthere can be significant
scheduling issues depending on the institution if an aborted
procedure means allocated theater time is unable to be utilized.
The yield of staging laparoscopy depends on many factors.
The type and stage of the malignancy affects the likely presence of imaging-occult metastases, as does the quality and
type of the imaging performed. The extent of the staging procedure is also importantwhether laparoscopic ultrasound,
peritoneal washings or trial dissection is included. It is also
obviously influenced by what findings are considered to contraindicate resection; for example, localized peritoneal disease
or porta hepatis nodes for colorectal liver metastases, or
involvement of the portal vein requiring vein resection and
grafting in pancreas cancer may not be considered contraindications to resection. The value of a positive staging laparoscopy also depends on whether any required palliative
procedures, such as biliary or gastric bypass in carcinoma of
the head of the pancreas, can be performed laparoscopically.
In adenocarcinoma of the pancreas, after high-quality CT
scanning, staging laparoscopy has been shown to identify

laparoscopic staging
A proportion of patients with hepatobiliary and pancreatic
malignancies will appear to be resectable on noninvasive

Figure 10.3 Peritoneal metastases at staging laparoscopy and carcinoma of the


head of the pancreas.

91

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


unresectability in 15% to 51% of patients, and spare 10% to
31% of patients an unnecessary laparotomy (51,5561). Laparoscopic ultrasound has been shown to add information in
12% to 14% of patients (6264). Patients with tumors larger
than 3 cm are more likely to have unsuspected metastases at
exploration (65), as are patients with a Ca 19.9 level greater
than 150 kU/L (66,67). Positive peritoneal lavage has been
found in 3% to 51% of patients (57,6876), and is more likely
in locally advanced or metastatic tumors (77), larger tumors,
and tumors of the body or tail (70,78). Positive peritoneal
cytology, which has the same prognosis as metastatic
disease (79), is the only marker of unresectability in 1% to
14% of patients (57,69,70,76). Tumors of the body and tail of
the pancreas are twice as likely as pancreatic head lesions to
have imaging-occult metastases (57,69). Imaging-occult
metastases are uncommon in nonpancreatic periampullary
tumors (60,80,81) and routine laparoscopy in these patients is
probably not indicated. Patients who on imaging have locally
advanced, unresectable pancreatic cancer should also be considered for staging laparoscopy, as those without metastatic
disease can be considered for chemoradiotherapy regimens
aimed at local control or even downstaging followed by resection, regimens which would incur unnecessary treatmentrelated morbidity for those with metastatic disease (69,77,82).
In colorectal liver metastases, laparoscopy will identify unresectable disease in 10% to 38% of patients, with a sensitivity of
39% to 75% (8390). Laparoscopy is more likely to be positive
in patients with a higher clinical risk score (83,86,91). In noncolorectal, nonneuroendocrine liver metastases, laparoscopy
has been reported to identify unresectable disease in 25% of
patients, with a sensitivity of 66% (92).
Staging laparoscopy is useful for patients with primary biliary malignancies. For patients with suspected resectable gall
bladder carcinoma on imaging, the yield for detecting unresectable disease is 56% to 62% (93,94), though the yield is less
for intrahepatic cholangiocarcinoma (93) at 36% and hilar
cholangiocarcinoma (9395) at 25%. The yield for hilar cholangiocarcinomas is higher for T2 or T3 lesions than for T1
lesions (94) (36% vs. 9%).
In hepatocellular carcinoma that is considered suitable for
curative resection, peritoneal dissemination is uncommon,
and standard laparoscopy is unlikely to add much information. Laparoscopy with laparoscopic ultrasound, however, can
identify the extent of the primary tumor, additional imagingoccult tumors, portal or hepatic venous tumor thrombus or an
inadequate hepatic remnant, with a yield for unresectability of
10% to 36% and a sensitivity of 63% to 96% (96100). The
results obtained will depend on the type and quality of preoperative imaging and the level of experience with laparoscopic
ultrasound.

laparoscopic palliative bypass


In patients with inoperable periampullary tumors, there is
often biliary and/or gastric obstruction that requires relief.
The traditional teaching in open surgery was to perform both
a biliary and gastric bypass whether or not the patient was
symptomatic. If at laparoscopy the tumor is found to be unresectable, in the absence of actual or impending biliary or

92

gastric outlet obstruction, it is not necessary to perform a palliative biliary or gastric bypass (101). In many instances, the
endoscopic approach is effective to relieve obstruction. Duodenal stenting is safer and provides a better quality of life than
laparoscopic gastrojejunostomy in the short term (102),
although laparoscopic gastrojejunostomy may provide a more
durable result for patients with a longer life expectancy (103).
ERCP with placement of a plastic biliary stent has a lower
morbidity than traditional open surgical bypass, although
plastic biliary stents have a tendency to occlude, resulting in
recurrent biliary obstruction requiring a repeat procedure
(104). Metallic stents, however, have a much higher patency
rate in the longer term, and can serve many patients for the
remainder of their survival (104106).
In some cases, however, stenting fails for technical reasons or
due to inability to access the ampulla. In these cases, a laparoscopic bypass is a useful option (107116), with the potential
for lower morbidity and shorter hospital stay than an open surgical procedure (113,115). A laparoscopic biliary bypass is most
easily performed as a stapled or sutured side-to-side cholecystojejunostomy. The main limitation of this approach is that the
confluence of the cystic and common hepatic ducts must
be well above the tumor to prevent recurrent biliary
obstruction (117). This can be confirmed at the procedure by
cholangiography via the fundus of the Gall bladdera Verres
needle with large syringe attached is used to empty the gall
bladder of bile, which is then filled with contrast to confirm
that the cystic duct confluence is more than 1 cm above the
level of the tumor. If this is not the case, an hepaticojejunostomy is constructed. A gastrojejunostomy is typically fashioned
in an antecolic, isoperistaltic stapled side-to-side manner.

laparoscopic pancreatectomy
Distal pancreatectomy is well suited to a laparoscopic approach.
The usual indication is a solid or cystic tumor of the tail of the
pancreas that is not clearly benign on preoperative imaging.
The procedure may involve en-bloc resection of the spleen and
splenic vessels; preservation of the spleen with preservation of
the splenic vessels; or preservation of the spleen without preservation of the splenic vessels with the spleen supplied from
the short gastric and gastroepiploic vessels (the Warshaw technique (118)).
For lesions close to the spleen, when splenectomy is necessary, the approach can be similar to laparoscopic splenectomy,
with the patient left side up, and the spleen and distal pancreas
mobilized from lateral to medial. After division of the short
gastric vessels and the gastrocolic omentum, the pancreas
can be divided en bloc with the splenic vessels using a
linear stapler.
For a medial to lateral approach, the pancreatic neck is
divided, either with a stapling device or with the harmonic
scalpel with subsequent suture closure of the pancreatic
stump. Where the splenic vessels are being resected, the
splenic vein is divided with a stapling device and the splenic
artery divided with a stapling device or locking clips. If the
splenic vessels are to be preserved, then the tail of the pancreas is dissected carefully from them with control of the
small vessels with clips and/or the harmonic scalpel or

LAPAROSCOPY IN HPB SURGERY


electrosurgical sealing device. Otherwise the dissection continues in the relatively avascular plane behind the splenic
vein. At this point, if the spleen is to be preserved with the
Warshaw technique, then the splenic hilum is divided with a
stapling device taking care to preserve the short gastric vessels, and the gastroepiploic arcade. Otherwise if the spleen is
to be resected, the dissection continues in this plane behind
the splenic vein to complete the mobilization of the spleen
and complete the resection. The specimen is retrieved in a bag
and a closed suction drain is placed.
Laparoscopic distal pancreatectomy has been shown to be a
safe procedure, with a shorter hospital stay and overall morbidity that is less than the open procedure (119124). The
main complication is a pancreatic fistula occurring in about
15% of patients, though this occurs at no greater rate than
with an open resection (120,124). The application of fibrin
glue to the stump (125) and the use of staple line mesh reinforcement (126) have both shown some benefit in small studies in reducing this rate, and in open surgery the placement of
a transampullary stent (127) has shown some benefit, as has
identification and direct suture of the main pancreatic
duct (128), although the optimal management of the pancreatic stump is still to be determined. Preservation of the spleen
by the Warshaw technique can be complicated by infarction of
the lower pole of the spleen (129,130).
Laparoscopic central pancreatectomy has been reported in
the literature (131) and successfully been performed twice by
one of the authors. The indication of a central tumor where
diabetes is a risk postoperatively is not common.
Laparoscopic enucleation of insulinomas has been reported
in small series but is associated with a significant rate of pancreatic fistula (129,132,133). Intraoperative ultrasound is
essential to ensure that the main pancreatic duct is not close to
the resection line.
Laparoscopic pancreaticoduodenectomy has been reported
in small numbers (134137). The procedure is feasible but
prolonged and difficult, and the potential role for this procedure remains to be determined.

laparoscopic liver resection


The laparoscopic approach to liver resections presents certain
technical challenges. It is a heavy solid organ that can be cumbersome to mobilize and manipulate, parenchymal transection requires the identification and control of large vessels
with the potential for significant bleeding, and the paucity of
external anatomical markers can make the maintenance of
surgical orientation to ensure a satisfactory oncologic clearance difficult.
Laparoscopic liver resection was initially reported in 1995 by
Rau (138), Cuesta (139), and Hashizume (140). Anatomic
resections in the form of left lateral sectionectomy were
reported in 1996 by Azagra (141) and Kaneko (142), formal
hemihepatectomies were reported in 1998 by Huscher (143),
and Cherqui (144) reported the first significant series of
30 patients in 2000. The largest series were recently reported
by Koffron (145) and Buell (146).
Dr. Joe Buell organized the first international consensus
meeting on laparoscopic liver resection, held in Louisville,

Kentucky in November 2008. Agreed definitions of laparoscopic liver surgery include the following:

Pure laparoscopic: where the liver resection is completed laparoscopically and the specimen removed
via a remote incision;
Hand assisted: where the surgeon operates with his
nondominant hand inside the abdomen, placed via
an airtight device, through which the specimen is
removed;
Hybrid liver resection (145): where the liver is mobilized laparoscopically and most of the resection is
done through a smaller than usual right upper quadrant incision;
Conversion: where the surgeon changes to an open
operation from one of the above. One can also convert from pure laparoscopic to hand assist or hybrid.

The most suitable cases for a laparoscopic approach are solitary small (<5 cm) lesions located in the peripheral segments
(26) of the liver. Larger lesions are acceptable if they are
pedunculated or located in the left lateral section. Multiple
lesions may be suitable if they can be resected with a single anatomic hepatectomy with a clear margin, but not where multiple
complicated or bilobar procedures are required. Hemihepatectomies can be considered for a laparoscopic approach where
the plane of transection and major structures (pedicles, hepatic
veins and inferior vena cava) are well clear of any lesions.
Lesions located in segments 7 and 8 are difficult to approach
laparoscopically for a tumorectomy as the costal margin limits
the approach angles of the instruments, and there is a real risk
of compromising the deep margin for fear of causing difficultto-control bleedingthey should only be considered for a
laparoscopic tumorectomy if they are particularly small and
superficial, otherwise they need to be considered for an open
procedure or a laparoscopic right hemihepatectomy.
The procedures are usually performed in the supine position, often with the surgeon standing between the legs. The
left lateral decubitus position is useful for lesions in segments
6 and 7, which enables better exposure of the right posterior
section of the liver. Hand ports may be used. These are most
useful in right sided resections where mobilization is difficult, either in nonanatomical resections with a posterior
tumor in the right lobe, or right hemihepatectomies with a
bulky right lobe. Good quality laparoscopic equipment is
vital. A good 10-mm laparoscopic right angle is also a very
important tool.
An initial laparoscopy is performed, and laparoscopic ultrasound is used to identify the lesions and their relationships to
the appropriate anatomy (Fig. 10.4). A tape can be placed
around the hepatic pedicle in readiness for a Pringle maneuver
if required; this is usually reserved for situations where bleeding is encountered rather than used routinely, and uses an
intermittent protocol (as the time of transection tends to be
longer than in open surgery). The gall bladder is resected
where indicated, but after division of the cystic duct and artery,
it may be left attached to the liver until later in the procedure
to help maneuver the liver, such that the gall bladder and
round ligament become the two handles of the liver. It is a

93

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

Figure 10.4 Laparoscopic ultrasound used to mark out resection line for a
tumor in segment 6.

useful point to divide the round ligament flush with the anterior abdominal wall such that there is not dangling tissue
irritatingly obstructing the view and dirtying the camera
through the whole procedure.
There are many methods of parenchymal transection: harmonic scalpel (Ethicon), Ligasure device (Covidien), Gyrus
(Gyrus ACMI), CUSA (Integra), TissueLink (Salient Surgical
Technologies), stapling devices, water jet, and metal clips. Each
have their advantages and disadvantages, and used appropriately each can have their place. Personal preference and experience as well as local teaching and availability determine the
choice. The various energy-delivery devices will not control
the large venous structures; these must be identified intraparenchymally and controlled with clips or stapling devices. It is
also prudent to individually control the large pedicular
branches. Stapling devices can be used en-masse across portions of the parenchyma to control the larger structures within,
but a degree of finesse is lost and unexpected bleeding can be
encountered. The combination of the harmonic scalpel for the
superficial 2 cm of dissection with the CUSA for the deeper
dissection is a good technique (147). A good alternative is the
Ligasure device, which when used with a modified technique
(closing while activating, using the cutting blade sparingly,
with gentle saline irrigation to prevent charring) can be used
to dissect out the larger intraparenchymal structures (148).
Left lateral sectionectomy begins with mobilization of the
falciform ligament, left coronary ligament, and lesser omentum to mobilize the left lobe. The parenchyma is divided so as
to expose the upper surface of the segments 2 and 3 pedicles
intrahepatically. The pedicles are then divided with a stapler.
The parenchymal transection is then completed to expose the
left hepatic vein intrahepatically, which is divided with a stapler. An alternative to this technique is mass stapling of the left
lateral section (149,150). Left lateral sectionectomy is particularly suitable to a laparoscopic approach and arguments have
been made that the laparoscopic approach should be used routinely for this resection (149,151).

94

Figure 10.5 Laparoscopic dissection of the right portal vein. The right hepatic
artery has been divided. The cystic duct has been divided and is used to retract
the bile duct. The right portal vein has been looped. The left portal vein is
clearly demonstrated and the right portal vein can be seen dividing into its
anterior and posterior branches.

For a left hepatectomy, the left liver is mobilized as above.


The left hepatic artery and left portal vein are dissected extrahepatically, demonstrating the line of demarcation. The parenchymal transection is then begun, opening the liver to allow a
good exposure of the left pedicle and sufficient space to introduce a stapling device to divide the left bile duct. The parenchymal transection is then continued, exposing the left hepatic
vein intrahepatically, which is divided with a stapling device to
complete the transection.
A right hepatectomy can be performed either with an anterior or a traditional approach. An anterior approach begins
with an extrahepatic dissection and division of the right
hepatic artery and right portal vein (Fig. 10.5). The parenchymal transection is then begun, opening the liver to allow an
intrahepatic division of the right bile duct. The parenchymal
transection is then completed down to the anterior surface of
the inferior vena cava. The minor hepatic veins are then
divided between clips, followed by the right hepatic vein and
hepatocaval ligament with stapling devices. The final step is
mobilization of the liver and division of the right coronary
ligament. In the traditional approach, there is the same extrahepatic division of the right hepatic artery and right portal
vein, with full mobilization of the liver and division of the
hepatocaval ligament and right hepatic vein before transection
of the parenchyma (Fig. 10.6). Laparoscopic right hepatectomy is a difficult procedure that requires expertise in both
laparoscopic and hepatic surgery.
The specimen is removed intact in a bag, either through the
hand port incision, a previous appendicectomy scar, or a
Pfannenstiel incision. After this period of desufflation, the
extraction incision is closed to allow re-establishment of the
pneumoperitoneum to confirm hemostasis, as bleeding may
have been tamponaded by the pressure of the pneumoperitoneum. In any type of laparoscopic liver resection, significant

LAPAROSCOPY IN HPB SURGERY

references

Figure 10.6 Mobilization of the right liver from the inferior vena cava.

bleeding can be encountered, and the surgeon must have the


requisite laparoscopic skills to be able to control this situation.
Good skills in laparoscopic suturing are essential. Conversion
to laparotomy may certainly be required, but immediate conversion is not always the best response. Venous bleeding is
often partly tamponaded by the pneumoperitoneum. The
bleeding source is identified and controlled with a grasper, and
hemostasis is achieved with suturing or a clip as appropriate. If
initial maneuvers are not successful then conversion is required
without persisting for too long or worsening the bleeding.
These are potentially dangerous situations that require both
skill and judgment.
Assessment of laparoscopic liver resection has been based
on series (144,147149,151173) and retrospective comparative studies (145,174185). These reports from expert centers
demonstrate that laparoscopic liver resection can be performed safely, and that despite a longer operating time there
is the potential for reduced hospital stay and reduced bleeding. Despite initial concerns, CO2 embolus occurs uncommonly. The oncologic results in nonrandomized studies have
been good (145,158,174177,180), but care must be taken in
interpreting these series, as those patients undergoing laparoscopic resection have been selected with smaller and fewer
tumors that would normally also infer a better prognosis.
There is a potential benefit in cirrhotic patients, with a lower
incidence of ascites postoperatively (147,176), as well as fewer
adhesions that facilitate subsequent transplantation (186).

conclusion
Laparoscopic approaches for the simplest of HPB procedures,
cholecystectomy, have literally exploded around the world.
More complex operations have been reported in small series,
but have not been taken up with the same enthusiasm. As technology improves, and the skill set of surgeons increases, it
seems inevitable to us that more and more will be done. As
long as basic oncologic principles are adhered to, and the surgical maxim of conversion if concerned is followed, patients
will continue to benefit from this exciting surgery.

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11

Cross-sectional imaging for HPB disorders (MRI and CT)


Lawrence H. Schwartz

overview
The maturation of surgery of the liver, biliary tract, and
pancreas as field unto itself has happened concomitantly
with, and partly as a result of, advances in cross-sectional
imaging. Rather than relying on expected anatomy based on
textbooks, surgeons can now plan operations based on the
precise anatomical details of each individual patient. The
ability to predict anatomical variations, which are present in
nearly one-half of the patients, has taken the element of
surprise out of the operating room and can help reduce
operative morbidity (1).
In this chapter, we briefly discuss the application of computed tomography (CT) and magnetic resonance imaging
(MRI) to the surgical management of disease of the liver, biliary tract, and pancreas. We begin by reviewing the relevant
cross-sectional anatomy of the organs being studied. Next, we
discuss the various techniques used to obtain high-quality
CT and MRI images of the liver, biliary tract, and pancreas.
Finally, we review the cross-sectional imaging characteristics
of important pathological entities commonly encountered by
surgeons caring for patients with diseases of the liver, biliary
tract, and pancreas.

cross-sectional anatomy
The effective use of cross-sectional imaging in the diagnosis
and treatment of disorders of the liver, biliary tract, and
pancreas mandates a strong understanding of anatomy. Developing this understanding of the complex three-dimensional
structures and being able to extrapolate from two-dimensional
representations requires a structured approach. A more
detailed description of relevant anatomy can be reviewed in
the previous chapters and elsewhere, therefore we will here
focus on the interpretation of cross-sectional anatomy and its
relation to in situ anatomy (2).
Liver and Biliary Tract
Segmental liver anatomy is the basis for modern liver surgery;
therefore, we provide a framework with which to define this
anatomy for each patient based upon cross-sectional imaging.
Cantlies plane, also known as the main portal fissure, is an
imaginary plane drawn from the gallbladder fossa toward the
inferior vena cava (IVC) that divides the anatomical right and
left lobes of the liver. The course of the middle hepatic vein
(MHV) is fairly constant and lies in this otherwise potentially
avascular plane; therefore, it can be used to delineate the two
lobes on cross-sectional imaging (3). The right hepatic vein
(RHV) defines the plane separating the anterior (segments 5
and 8) and posterior sectors (segments 6 and 7) of the right
lobe. While the plane of the left hepatic vein (LHV) separates
the anterior and posterior sectors of the left lobe, its anatomy
is highly variable, making it a less useful landmark.

100

In contrast to hepatic veins, which course between liver segments, portal veins and their accompanying artery and bileduct branches define the center of each segment. The main
portal vein (PV) typically branches extrahepatically into the
left and right portal veins (LPV and RPV, respectively); the
RPV divides into the anterior and posterior sectoral branches,
while the LPV enters the umbilical fissure and provides
branches to the left lobe. While this describes standard anatomy, approximately one-third of patients have variant portal
venous anatomy (Table 11.1) (4).
In standard arterial anatomy the common hepatic artery
arises from the celiac axis and divides into the gastroduodenal
artery and the proper hepatic artery. The proper hepatic artery
then gives rise to the right and left hepatic arteries. However,
nearly one-half of patients have variations in their hepatic
arterial system. A list of arterial variants demonstrated in a
recent study is shown in Table 11.2 (1).
Pancreas
The pancreas is divided into the head, uncinate process, neck,
body, and tail. These divisions are based upon external landmarks such as the superior mesenteric vein (SMV), which lies
under the neck of the gland and defines the separation between
the head and the body. The pancreas has a long course through
the retroperitoneum and is intimately associated with multiple organs including the transverse colon, stomach, duodenum, and spleen. Additionally, it has a close relationship with
the portal venous system that, in part, defines the resectability
of pancreatic masses. The pancreas has a rich arterial supply
that comes from multiple branches of the celiac and superior
mesenteric arteries. As in hepatic surgery, preoperative determination of variations in peripancreatic vascular anatomy can
greatly aid in operative planning.

technique
Liver and Biliary Tract
CT is commonly used as the primary modality to detect, characterize, and follow hepatic or biliary pathology. Modern
multislice helical CT scanners allow for the rapid acquisition
of large volumes of data in a single patient breath-hold, thereby
allowing for the construction of high-resolution axial, coronal,
sagittal, and three-dimensional images.
Noncontrast CT allows us to make determinations about the
character of the liver parenchyma based on changes in density.
This is useful for detecting global hepatic abnormalities;
however, it does not allow for the precise delineation of hepatic
vascular structures nor the detection and characterization of
subtle hepatic masses. CT examination of the liver, therefore,
relies on iodinated contrast enhancement. Accurate CT imaging
requires achieving maximal differences in attenuation between
tissues, therefore understanding the contrast enhancement

CROSS-SECTIONAL IMAGING FOR HPB DISORDERS (MRI AND CT)


characteristics of the liver and each type of liver tumor is essential. The liver receives approximately 20% of its blood from the
hepatic artery and the remaining 80% from the portal vein.
Since intravenously injected contrast reaches the liver via the
hepatic artery before it does via the portal vein, and takes some
time to reach a state of equilibrium, a triphasic CT scan based
on hepatic arterial, portal venous, and equilibrium phases is
favored for examination of the liver.
Although CT remains the most commonly used modality
for obtaining cross-sectional images of the liver because of its
lower cost and its greater ease of interpretation by clinicians,
the indications for liver MRI continue to grow. As compared
with triphasic liver CT, liver MRI has the advantages of not

Table 11.1 Anatomic Variations in Portal Vein Anatomy in


200 Patients
Patients
Type

Portal vein variant

No.

1
2
3(Z)

Standard anatomy
Trifurcation
Right posterior portal vein as first
branch of main portal vein
Segment VII branch as separate
branch of right portal vein
Segment VI branch as separate
branch of right portal vein
Other

130
18
26

65
9
13

12

12

4
5

exposing patients to ionizing radiation, a greater measure of


safety in patients with renal insufficiency, and an improved
ability to characterize certain types of lesions. However, MRI is
costly, more time intensive for patients, and contraindicated in
patients with certain metal implants.
In many centers, magnetic resonance cholangiopancreatography (MRCP) has nearly replaced diagnostic percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde
cholangiopancreatography (ERCP), thus reserving the latter
studies for situations in which there is therapeutic intent or in
which there is a need for tissue diagnosis. Using heavily
T2-weighted sequences, MRCP represents stationary water with
high signal intensity (5). As MRCP does not require the administration or biliary excretion of contrast, it works well even in
the setting of hepatic dysfunction or obstructive jaundice.
Pancreas
As for liver and biliary tract imaging, contrast-enhanced CT
remains the primary modality used in the setting of pancreatic
disease; however, MRI again has some advantages. While CT
has higher spatial resolution, MRI may have a better ability to
characterize lesions based on tissue composition.
Optimal CT imaging of the pancreas relies on the ability of
multidetector CT scanners to rapidly capture large volumes of
information during specific time periods after IV contrast
administration. Thin slices and the ability to reformat images
in multiple axes are helpful in preoperative preparation. Furthermore, water is administered as an oral contrast agent to
improve differentiation among bowel, pancreas parenchyma,

Table 11.2 Frequency of Different Arterial Variants Seen at CT Angiography in 371 Patients
Type of finding
Classic celiac arterial anatomy
Replaced RHA off SMA
Replaced LHA off LGA
Artery to segments 2 and 3 off LGA
Artery to segments 4A and 4B off RHA
Trifurcation of CHA into GDA, RHA, and LHA
RHA off celiac axis
Accessory LHA off LGA
LGA directly oft abdominal aorta
CHA off SMA
CHA directly off the aorta
RHA off GDA
Accessory RHA
Common trunk of celiac axis and SMA
Medial and lateral branches separate off CHA
LHA off CHA
GDA off RHA
SMA gives rise to GDA
LHA off celiac axis
RHA off aorta
Segment 4 branch off GDA
Extrahepatic branching of RHA into anterior and posterior with
artery to segment 4 off anterior division of RHA

No. of findings (o = 394|)


188
54
30
19
17
15
13
13
11
6
6
5
3
2
2
2
2
2
1
1
1
1

% of patients (n = 371)
51
15
8
5
5
4
4
4
3
2
2
1
1
<1
<1
<1
<1
<1
<1
<1
<1
<1

Note: Twenty patients had two variants seen at CT and one patient had four variants.
Abbreviations: LHA, left hepatic artery; RHA, right hepatic artery; LGA, left gastric artery; SMA, superior mesenteric artery; CHA, common hepatic artery;
GDA, gastroduodenal artery. Source: Reprinted with permission from Ref. 4.

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


and blood vessels. Importantly, modern CT scans may have
even greater ability than endoscopic ultrasound to determine
the involvement of major vascular structures by periampullary
pancreatic cancers (6).
MRI is of particular use in patients with contrast allergies or
renal insufficiency, although optimal imaging with MRI still
requires the administration of gadolinium as a contrast agent.
As for biliary pathology, MRCP is often useful in assessing
biliary and pancreatic ductal obstruction due to pancreatic
masses. In clinical practice, these techniques are often supplemented by ERCP and endoscopic ultrasound.

cross-sectional imaging characteristics


of liver and biliary tract lesions
Cysts
Nonparasitic simple hepatic cysts are fluid-filled thin-walled
benign lesions that have no malignant potential, and are found
in 1% to 5% of the population. Although treatment of large
hepatic cysts may be undertaken to relieve compressive symptoms, most cysts require no treatment at all. Hepatic cysts are
recognized on CT imaging by their spherical or near-spherical
shape, water-attenuation fluid contents, and barely visible wall
that lacks contrast enhancement. By MRI, simple cysts are
homogeneous and have low-T1 and high-T2 signal intensity.
Multiple hepatic cysts may also be present in the setting of
polycystic kidney disease. Distinguishing simple cysts from
cystadenoma, which is a very rare tumor, is important in
that the latter lesion has the potential to compress the bile
ducts, bleed, or develop into a cystadenocarcinoma. On crosssectional imaging, cystadenomas may demonstrate internal
septations and a thick wall that enhances with contrast administration (Fig. 11.1).
Echinococcal or hydatid cysts are common in certain parts
of the world that are endemic for this echinococcus granulosis,
which is a parasitic disease transmitted from dogs. Hydatid
cysts are recognized as being well-circumscribed cystic lesions
that often contain multiple smaller cysts known as daughter
cysts. As the primary treatment for hydatid disease consists of
administering the anthelmintic agent albendazole, recognition
of this entity based on imaging characteristics is essential.

(A)

Hepatic Hemangioma
Hepatic hemangiomata are common vascular lesions of the
liver that receive their blood supply from the hepatic artery.
Hemangiomata rarely cause symptoms; however, giant ones
can be associated with abdominal pain or other compressive
symptoms (7). Hemangiomata are diagnosed based on their
nodular, clump-like pattern of early arterial enhancement on
CT (Fig. 11.2). Although small ones are fairly homogeneous in
appearance, large hemangiomata may have a heterogeneous
appearance due to areas of thrombosis. MRI is the most accurate imaging modality for diagnosing hepatic hemangiomata.
On T2-weighted imaging, they are hyperintense and have a
lobulated appearance. Administration of gadolinium again
shows early peripheral nodular enhancement.
Focal Nodular Hyperplasia
Focal nodular hyperplasia (FNH) is a common benign liver
tumor made up of all elements of the hepatic parenchyma.
FNH are completely benign and rarely, if ever, lead to symptoms. However, the fibrolamellar variant of hepatocellular carcinoma may be mistaken for FNH based on similar imaging
characteristics (8). Therefore, accurate identification of FNH
is of paramount importance.
On pathological examination, FNH typically have a central
scar that may be demonstrated on cross-sectional imaging.
Contrast-enhanced CT show rapid homogeneous enhancement during the arterial phase with reduced attenuation during the portal venous phase (Fig. 11.3). MRI imaging of FNH
reveals isointensity or slight T1 hypointensity or T2 hyperintensity, with a central scar that has even less T1 intensity or
more T2 intensity (9). Contrast administration shows early
enhancement with delayed enhancement of the central scar.
Hepatocellular Adenoma
Hepatocellular adenomas are benign proliferations of hepatocytes with a dramatically increased prevalence in patients with
a history of oral contraceptive use. Although they are benign
lesions, resection of hepatocellular adenomas is recommended
because of their propensity for hemorrhage and, albeit rare,
risk of malignant transformation. Adenomas are recognized

(B)

Figure 11.1 Biliary cystadenoma. (A) T2- and (B) postcontrast T1-weighted images of a biliary cystadenoma hanging off the inferior portion of the right lobe of
the liver. Arrows indicate solid enhancing component of mass distinguishing this from a simple cyst.

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CROSS-SECTIONAL IMAGING FOR HPB DISORDERS (MRI AND CT)

(A)

(B)

Figure 11.2 Hemangioma. (A) T1-weighted postcontrast imaging reveals a nodular peripheral enhancement (black arrow) pattern in the early arterial phase that
is characteristic of hemangiomas. (B) T2-weighted imaging reveals a hyperintense, lobulated lesion.

(A)

(B)

(C)

(D)

Figure 11.3 Focal Nodular Hyperplasia (A) T1-weighted precontrast image is isointense to hepatic parenchyma (B) T2-weighted image is also isointense to hepatic
parenchyma except the central scar (arrow), which is bright (C) T1-weighted postcontrast image in the arterial phase demonstrates homogenous, hyperintense
enhancement with the central scar enhancing on (D) delayed postcontrast images.

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


on CT as hypervascular, heterogeneous lesions during arterial
phase that become isodense or hypodense during the portal
venous phase. MRI also shows hepatocellular adenomas to be
heterogeneous, with T1 hyperintensity due to the presence of
fat or hemorrhage and typically show arterial phase enhancement as with CT.
Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) ranks among the most common causes of cancer-related mortality worldwide; however,
its incidence is markedly variable based on geography and
prevalence of hepatitis B and C virus infection (10). As it
occurs most commonly in the setting of cirrhosis, its radiological diagnosis can be challenging. This is due to the presence of fibrosis and regenerative nodules that can be difficult
to distinguish from dysplastic nodules or HCC. Contrastenhanced CT helps provide some distinction, as small dysplastic nodules or HCC that can be mistaken for regenerative
nodules typically enhance during the arterial phase and have
contrast washout in the delayed venous phase (11). Larger
HCC are more heterogeneous in their appearance and may
not demonstrate contrast enhancement. MRI adds sensitivity
to the diagnosis by showing differences in signal intensity
between areas of carcinoma and cirrhotic liver (12). Although
HCC are typically hypointense on T1-weighted images, welldifferentiated HCC may be hyperintense. T2-weighted images
typically show HCC as hypointense lesions, however, this is
variable as well. HCC usually enhance with gadolinium
administration (Fig. 11.4).
Fibrolamellar Carcinoma
Fibrolamellar carcinoma (FLC) is a rare malignant tumor of
the liver that typically arises in the absence of cirrhosis in
relatively young patients (13). FLC is thought to be a variant of
HCC, and is therefore also referred to as fibrolamellar HCC.
On CT, FLC are usually large, hypoattenuating tumors with
heterogeneous contrast enhancement and a nonenhancing
central scar. The central fibrous scar usually show low signal
intensity on both T1-weighted and T2-weighted images.
Accurate diagnosis is essential since FLC may mimic FNH on
cross-sectional imaging due to the presence of a fibrous central scar on both.
Cholangiocarcinoma
Adenocarcinoma that develops from epithelial cells lining the
intrahepatic and extrahepatic bile ducts is termed cholangiocarcinoma. Hilar cholangiocarcinomas (Klatskin tumors),
which arise at the confluence of the right and left hepatic ducts,
are the most common type and typically present with jaundice
(14). CT or MRI of patients with hilar cholangiocarcinoma
shows intrahepatic biliary ductal dilatation, often in association with unilobar parenchymal atrophy, bile duct crowding,
and portal vein impingement. An associated mass lesion may
or may not be present, while a more prognostically favorable
papillary variant may show a nodular mass within the biliary
system (15). Extrahepatic cholangiocarcinoma, which arises
in the common hepatic or common bile ducts, also presents
with jaundice. Cross-sectional imaging demonstrates both

104

intrahepatic and extrahepatic biliary ductal dilatation. Again, a


mass lesion is rarely present, although papillary lesions are possible in this location as well. More commonly, the distal bile
duct will show an area of focal thickening that enhances with
contrast administration. Peripheral (intrahepatic) cholangiocarcinoma has an appearance on cross-sectional imaging that is
more similar to that of more commonly encountered liver
tumors. Biliary ductal dilatation is only focal in association
with a low attenuation mass that shows peripheral enhancement (Fig. 11.5).
Gallbladder Carcinoma
Gallbladder carcinoma is a highly aggressive tumor that is
notable for its highly variable incidence. Early gallbladder carcinoma may have few findings on cross-sectional imaging. CT
of early lesions may demonstrate focal gallbladder-wall thickening or a polypoid mass within the lumen of the gallbladder.
More advanced tumors may show a hypoattenuating mass in
or replacing the gallbladder, which may be associated with
hepatic involvement or biliary ductal dilatation. T2-weighted
MRI images show heterogeneous signal intensity with irregular contrast enhancement (16) (Fig. 11.6).
Metastatic Cancer to the Liver
The most common indication for liver resection in the western world is metastatic disease, especially from colorectal
cancer. Liver metastases from colorectal cancer, as well as
those from other GI malignancies, are typically characterized
by low attenuation relative to normal liver parenchyma;
however, there is high variability in their appearance.
Colorectal liver metastases are most readily appreciated on
portal venous phase CT (Fig. 11.6), and have variable levels
of rim enhancement. By contrast, neuroendocrine (Fig. 11.7)
and other hypervascular metastases tend to show early
arterial enhancement (17). MRI may help to characterize
liver metastases, which are typically of low signal intensity on
T1-weighted images and high signal intensity on T2-weighted
images.

cross-sectional imaging characteristics


of pancreatic lesions
Cysts
The widespread use of high-quality abdominal cross-sectional
imaging for a variety of indications has lead to an increased
recognition of cystic lesions of the pancreas. Cystic pancreatic
lesions may be non-neoplastic, as in the case of pseudocysts, or
can be neoplasms that are completely benign, premalignant, or
frankly cancerous. Given the broad differential diagnosis of
pancreatic cysts, determining their histological origin, while
challenging, is of paramount importance in deciding on management, especially for tumors greater than 3 cm in diameter
(18,19).
Pseudocysts, which are common sequelae of acute pancreatitis, are the most common cystic lesions of the pancreas.
As such, differentiating pseudocysts from cystic neoplasms of
the pancreas prior to treatment is desirable. Since a clinical
history of prior episodes of acute pancreatitis is not perfectly
correlated with the diagnosis of pseudocyst, radiological

CROSS-SECTIONAL IMAGING FOR HPB DISORDERS (MRI AND CT)

(A)

(B)

Figure 11.4 Hepatocellular carcinoma. (A) Arterial phase CT image demonstrating a dominate right-lobe mass. (B) Note the change in enhancement on the portal
venous phase of imaging.

(A)

(B)

Figure 11.5 Gallbladder carcinoma. T2-weighted MRI (A) axial and (B) coronal images demonstrate a solid mass in the gallbladder with hyperintense surrounding
liver parenchyma consistent with local extension of the tumor into the liver parenchyma.

differentiation is necessary. The presence on MRI of dependent debris within a cystic pancreatic lesion has been found to
be highly suggestive of the diagnosis of pseudocyst (20).
Serous cystadenoma (SCA) are the most common benign
neoplasm of the pancreas and are typically asymptomatic
findings, however a proportion of patients do present with
symptoms due to mass effect (21). SCA are comprised of multiple smaller cysts and may have a variable appearance based
on the size of the cysts that comprise them. In fact, microcystic
tumors may have an appearance on CT more consistent with
that of a solid tumor. MRI and ultrasound may be helpful in
defining the cystic nature of such tumors. Since asymptomatic
SCA do not require treatment, differentiating them from other
malignant or premalignant lesions is critical. In the event that
imaging characteristics are nondiagnostic, biopsy or resection
may be indicated.
Intraductal papillary mucinous neoplasms (IPMN) are premalignant tumors arising from the main pancreatic duct or its

Figure 11.6 Colorectal cancer metastasis. Irregular hypodense central lesion


on contrast-enhanced CT represents a colorectal liver metastasis.

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

Figure 11.7 Neuroendocrine metastases. (A) Innumerable hypodense neuroendocrine metastatic nodules with variable levels of rim-enhancement on portal
venous phase contrast-enhanced CT. (B) Coronal slice demonstrates direct extension of tumor into the portal vein (arrow).

(A)

(B)

Figure 11.8 Intraductal papillary mucinous neoplasm (IPMN). (A) T1-weighted postcontrast imaging reveals a low-intensity multilocular lesion in the head and
uncinate process of the pancreas suspicious for a side-branch IPMN. (B) T2-weighted images demonstrate high signal intensity.

branches. IPMN contain epithelium ranging from benign adenoma to invasive adenocarcinoma. IPMN are differentiated
based on whether they arise from side-branches or from the
main pancreatic duct, with the latter having a higher potential
for progressing to invasive malignancy. Cross-sectional imaging
reveals a cystic region within or adjacent to the pancreatic
parenchyma that may demonstrate continuity with the pancreatic ductal system. Factors that influence the decision to perform pancreatectomy for IPMN include size, growth, and the
presence of fibrous septations or solid components. Mucinous
cystic neoplasms (MCN) are less common lesions, typically seen
in women, which are characterized by ovarian-type stroma.
MCN are also felt to be premalignant lesions, therefore their
resection is recommended. MCN have imaging characteristics
similar to those of IPMN, with the absence of a definable connection to the main pancreatic ductal system (Fig. 11.8).
Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors (PNET), also known as islet
cell tumors, are rare malignant neoplasms that have a relatively
slow growth rate. While most PNET are nonfunctional, they

106

may secrete hormones that lead to clinical symptoms, especially in the setting of metastatic disease to the pancreas. PNET
are typically hypervascular lesions that show early arterial
phase enhancement on CT, but may be isodense on portal
venous phase. Small functional tumors may prove difficult to
identify on cross-sectional imaging studies, therefore accurate
timing of imaging to the arterial phase of enhancement is
important. Similarly, MRI imaging of PNET usually demonstrate high signal intensity on T2-weighted images and low
intensity on T1-weighted images with significant contrast
enhancement (22) (Fig. 11.9).
Solid Pseudopapillary Tumor
Solid pseudopapillary tumor (SPT) of the pancreas is a rare,
indolent tumor that most commonly affects women in the
first three decades of life. Although it has metastatic potential,
malignant behavior is uncommon, therefore resection is considered curative. CT imaging is varied and may demonstrate a
large lesion with internal hemorrhage or cystic degeneration.
While vascular encasement, pancreatic ductal dilatation, and
hepatic metastases are seen only in the carcinomatous variant

CROSS-SECTIONAL IMAGING FOR HPB DISORDERS (MRI AND CT)

Figure 11.9 Neuroendocrine pancreatic tumor. A well-preserved fat plane is


seen separating this large hypervascular neuroendocrine tumor in the head of
the pancreas from the superior mesenteric/portal vein. Areas of hypoattenuation towards the middle of the tumor are suggestive of central ischemia.

of this tumor, more typical findings based on size, capsule


thickness, internal composition, and calcification pattern do
not help to differentiate benign and malignant lesions (23).
Acinar Cell Carcinoma
Although acinar cells comprise the bulk of pancreatic tissue,
acinar cell carcinomas (ACC) are very uncommon. ACC are
typically well-circumscribed tumors that may be lobulated
and may be heterogeneous or homogeneous in appearance on
cross-sectional imaging (24). ACC range from being completely
solid to mostly cystic with at least some solid components and
central necrotic areas may be seen. Biliary or pancreatic ductal
dilatation is occasionally seen. Contrast-enhanced CT shows
homogeneous enhancement of solid components, but less
than that of the surrounding pancreas. T2-weighted MRI
images may show hyperintense signal in relation to pancreatic
parenchyma.
Pancreatic Adenocarcinoma
Pancreatic adenocarcinoma, commonly referred to as pancreatic
cancer, is the most common malignant neoplasm of the pancreas.
It is a highly aggressive malignancy that carries with it an extremely
high mortality rate, having an incidence that nearly equals its
mortality rate. Because of the biologically aggressive nature of
pancreatic cancer, the majority of patients present with metastatic
or unresectable disease. Contrast-enhanced CT usually shows a
hypoattenuating poorly defined mass with dilatation of the pancreatic duct distally and, in the case of tumors of the pancreatic
head, biliary ductal dilatation as well. Biliary and/or pancreatic
ductal dilatation may also be seen in the absence of an identifiable
mass, and dilatation of both of these ductal systemsthe double
duct signis a classic sign of adenocarcinoma of the head of the
pancreas. The double duct sign is not, however, pathognomonic
for pancreatic cancer and may be associated with benign processes (25). MRI has the advantage of being usable in patients
with diminished renal function and can be combined with MRCP
to provide detail about the biliary and pancreatic ductal systems
in a noninvasive fashion (Fig. 11.10).
The primary determinants of the resectability of pancreatic
lesions inevitably relate to vascular involvement, since the

Figure 11.10 Pancreatic adenocarcinoma. Contrast-enhanced CT reveals a


hypointense solid-appearing mass in the tail of the pancreas. This appearance
on cross-sectional imaging is characteristic of pancreatic adenocarcinoma.

pancreas is intimately associated with the portal venous system and in close proximity to the celiac artery and superior
mesenteric artery (SMA). High-quality cross-sectional imaging clearly defines these relationships and predicts the likelihood of successful resection.
Metastatic Cancer to the Pancreas
In contrast to the liver, the pancreas is a rare site of metastatic
disease. Although multiple types of cancer have been reported
to metastasize to the pancreas, renal cell carcinoma, nonsmall
cell lung carcinoma, and lymphoma are the most common
sources of isolated pancreatic metastases. Renal cell carcinoma
metastases to the pancreas are typically well-circumscribed,
arterial-enhancing lesions, while other histologies tend to be
more diffuse and variable in enhancement patterns.

conclusions
CT and MRI have become essential components in the diagnosis, perioperative management, and follow-up of hepatic,
biliary, and pancreatic pathology. Therefore, the ability to
appropriately order and interpret these studies, in consultation with radiologists, is a prerequisite to the surgical management of patients with such diseases.

references
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of celiac and superior mesenteric artery variants in patients undergoing
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2. Blumgart LH. Surgery of the Liver, Biliary Tract, and Pancreas, 4th edn.
Philadelphia, PA: Saunders Elsevier, 2007.
3. Kamel IR, Lawler LP, Fishman EK. Variations in anatomy of the middle
hepatic vein and their impact on formal right hepatectomy. Abdom Imaging 2003; 28(5): 66874.
4. Covey AM, Brody LA, Getrajdman GI, Sofocleous CT, Brown KT. Incidence, patterns, and clinical relevance of variant portal vein anatomy. AJR
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5. Adam A, Dixon AK, Allison DJ, Grainger RG. Grainger & Allisons Diagnostic Radiology: a Textbook of Medical Imaging 5th edn. Edinburgh:
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diagnosis of liver tumors with central scars by using specific CT criteria.
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9. Hussain SM, Terkivatan T, Zondervan PE, et al. Focal nodular hyperplasia:
findings at state-of-the-art MR imaging, US, CT, and pathologic analysis.
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2008; 88(6): 140928, xxi.
15. Jarnagin WR, Bowne W, Klimstra DS, et al. Papillary phenotype confers
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16. Schwartz LH, Black J, Fong Y, et al. Gallbladder carcinoma: findings at MR


imaging with MR cholangiopancreatography. J Comput Assist Tomogr
2002; 26(3): 40510.
17. Tamm EP, Kim EE, Ng CS. Imaging of neuroendocrine tumors. Hematol
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138(1): 315.

12

Liver metastases: detection and imaging


Valrie Vilgrain, Ludovic Trinquart, and Bernard Van Beers

The liver is the second most frequent site of metastases, after


lymph nodes, providing a very suitable environment for the
growth of metastases because of its rich blood supply from the
systemic and splanchnic system. The overall extent of liver
involvement in cancer patients is unknown but liver metastases have been found in 30% to 70% of patients who die because
of cancer, depending on their primary tumor (1).
Liver metastases frequently arise from colorectal cancer
(CRC), with 15% to 20% of patients presenting with synchronous liver metastases and another 15% developing metachronous metastases to the liver within five years (2,3). But unlike
many other types of cancers, the presence of distant metastases
from CRC does not necessarily preclude curative treatment. In
fact, CRC metastases are confined to the liver in 25% of
patients (4). This confinement of metastatic disease to the liver
has allowed progress in the treatment of these patientsvia
hepatic resection, regional chemotherapy, and thermoablative
treatments, and the benefits of such approaches are demonstrated by the fact that survival of up to 25% of patients 10 year
after resection of these metastases is possible.
Isolated liver metastases also often arise from gastric and
pancreatic cancersbecause of the portal venous drainage
to the liverand less frequently from breast or lung cancers.
But most non-CRC liver metastases are associated with distant metastatic spread to other organs and so require a more
systemic therapeutic approach. However, metastases confined to the liver may also be seen in ocular melanoma, breast
cancer, neuroendocrine tumors, renal cell cancers, and some
sarcomas (57).
In this context, the goal of imaging for liver metastases is
twofold: first to establish an early and accurate diagnosis of
liver metastases, second to stage preoperatively those patients
with liver metastases confined to the liver, especially when the
primary tumor is CRC. The diagnostic value of ultrasound
(US), contrast-enhanced US, multidetector computed tomography (CT), and magnetic resonance (MR) imaging with nonspecific gadolinium chelates and liver-specific contrast agent is
discussed. Pitfalls and limitations of imaging are shown. Lastly,
the role of imaging in assessing number, localization, and size
of metastases to determine resectability is emphasized.

The role of Doppler techniques is often limited because flow


signals in liver metastases are usually too low to be detected
except in markedly hypervascular liver metastases.
Because there are no specific features of metastases at conventional US, the differentiation of a single metastasis from
other lesions is usually not possible but on the other hand, US
is helpful to characterize benign lesions such as hepatic cysts
and hemangiomas in oncological patients. While in many
European countries, US was the recommended imaging
follow-up method, CT or MRI is nowadays preferred in oncological patients.

The principle of this technique is to increase the lesion-to-liver


contrast, using intravascular microbubble contrast agents,
which allows enhanced detection of smaller liver metastases
not seen on conventional US. Most contrast agents used
nowadays provide strong and persistent signal enhancement
due to harmonic resonance at low mechanical index, where
minimal or no bubble destruction occurs. Examination
includes a continuous evaluation of the lesion enhancement
during the arterial (1530 seconds delay), portal venous
(3060 seconds delay), and delayed (23 minutes delay)
phases. Most liver metastases are hypovascular and exhibit
no or minimal enhancement on the arterial phase. Interestingly, whatever the lesion enhancement is on the arterial
phase, metastases show nonenhancing defects on the delayed
phase, which seem to be the most useful determinant for
both lesion detection and characterization (Fig. 12.1). This
strong washout sign is caused by the biokinetics of the US
contrast agents that are purely vascular effects; conversely to
nonspecific CT and MR contrast agents that spread into the
interstitium. Indeed, the use of contrast agents improves the
sensitivity of US in detecting individual lesions by about
20% in comparison to baseline, independent of the type of
contrast agent used (9).
Contrast-enhanced US imaging is technically successful in
most patients except those with severe obesity and marked
steatosis in whom penetration of contrast-specific imaging is
limited.

imaging techniques

computed tomography

Ultrasound
Liver metastases are generally multiple, spherical, and have
well-defined margins. Most lesions are hypoechoic. The most
common hyperechoic metastases are observed in patients with
CRC or neuroendocrine tumors. Large lesions often have
more central hypoechogenicity related to areas of necrosis. A
hypoechoic halo is seen surrounding the lesions in 40% of
cases (8). More rarely, liver metastases may appear as diffuse
infiltration.

Computed tomography (CT) is the most commonly used


imaging modality for both detection and characterization of
liver metastases. Multidetector helical CT is now the standard technique. It reduces the scan time, with high coverage
and high-quality 3D reconstructions. The examination
comprises of an unenhanced scan and, after intravenous
administration of nonionic iodine contrast medium, two
acquisitions at the late arterial phase and the portal venous
phase. During the latter, the liver parenchyma enhances

contrast-enhanced ultrasound

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

(C)
Figure 12.1 (AC) Portal-phase CT shows a small liver tumor that is not characteristic of liver metastasis. This lesion is homogeneous and hyperechoic on
ultrasound (B). Portal-phase contrast-enhanced ultrasound demonstrates washout, which is highly suggestive of liver malignancy (C).

the arterial phase. A key finding is the presence of a halo (11),


which has been shown as a quite sensitive and specific finding for liver metastases. However, unenhanced, arterial-phase
and delayed-phase imaging (which is optional) are helpful
for differentiating benign lesions such as cyst, hemangioma,
or hepatocellular tumors from metastases.

magnetic resonance imaging

Figure 12.2 Portal-phase CT demonstrating multiple heterogeneous lesions


suggestive of liver metastases.

and it increases the lesion conspicuity of hypovascular


tumors (10) (Fig. 12.2). Most liver metastases are hypoattenuating and hypovascular on unenhanced scans, meaning
that they are better seen on the portal venous phase than on

110

The routine magnetic resonance (MR) imaging protocol


includes nonenhanced T1- and T2-weighted pulse sequences
and postcontrast sequences. On T1-weighted images, most
liver metastases are hypointense, but isointense lesions are
seen in approximately 10% of patients (12). Hyperintense
liver metastases are very uncommon but may be seen in melanoma. On T2-weighted images, liver metastases are most
commonly moderately hyperintense, whereas the remnants
are isointense or markedly hyperintense (12). The areas of
marked hyperintensity correspond to cystic changes or
necrosis (12). It seems that the signal intensity on T2-weighted
images is not related to metastases from a specific primary
neoplasm.
Contrast agents can improve diagnostic accuracy. Two
groups of MR contrast agents may be used: nonspecific gadolinium chelates whose biokinetics are similar to iodine
contrast agents, and liver-specific contrast agents, either for

LIVER METASTASES: DETECTION AND IMAGING

(A)

(B)

(C)

(D)

Figure 12.3 (AD) MR imaging of a colorectal metastasis. The tumor is hyperintense on T2- and hypointense on T1-weighted imaging (A and B). Note the peripheral
halo on portal-phase T1-weighted imaging and the delayed enhancement due to fibrous stroma (C and D).

reticuloendothelial system (ferumoxides) or hepatobiliary


captation (Mn-DPDP or specific hepatobiliary gadolinium
chelates). Briefly, the nonspecific gadolinium chelates are
used for lesion characterization, while the others have been
proposed for preoperative staging. The principle of the latter
is to increase the lesion-to-liver contrast by decreasing markedly the signal of the liver on T2 sequences (ferumoxides) or
increasing it on T1-weighted sequences (13). Some authors
have also proposed double-contrast MR combining specific
and nonspecific contrast agents.
Similarly to CT, nonspecific gadolinium MR imaging
should include baseline precontrast images and sequential acquisitions at arterial, portal, and equilibrium
phases. In a large series of 516 liver metastases from various tumors in 165 consecutive patients, most liver
metastases were hypovascular (64% of all patients and
91% of patients with colon cancer) ( 12 ). A hypervascular
pattern of enhancement was identified in 36% of
patients. During the arterial phase, peripheral ring
enhancement was seen in 72% of patients. On the portal
venous and delayed phase, incomplete central progression of lesion enhancement was found in two-thirds of
patients ( 12 ) ( Fig. 12.3 ). Peripheral washout in metastases on delayed-phase images was identified in one-third

of patients with hypervascular metastases and almost


never in hypovascular metastases ( 12 ) ( Fig. 12.4 ). After
administration of liver-specific contrast agents, liver
metastases that lack functioning hepatocytes or Kupffer
cells do not enhance postcontrast, resulting in improved
lesion conspicuity ( 14 ).
Diffusion-weighted MR imaging is quite interesting in liver
metastases. Nasu et al. (15) have shown increased detection of
metastatic lesions with a combination of diffusion-weighted
imaging and precontrast T1- and T2-weighted imaging when
compared with liver-specific contrast MR imaging. Parikh
et al. have shown that diffusion-weighted sequences were as
accurate as T2-sequences for characterization of focal liver
lesions including metastases (16) (Fig. 12.5).

positron emission tomography


Conversely to the other imaging modalities, which give more
morphologic than functional information, positron emission tomography (PET) imaging is essentially functional
imaging and provides a physiological survey for hypermetabolic tumors. PET scanning after administration of [18F]
2-fluoro-2-deoxyglucose (FDG) is based upon higher glycolytic activity of many tumors compared to normal tissue.
[18F]FDG is transported into cells and phosphorylated by

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


the enzyme hexokinase to [18F]FDG-6-phosphate, which
cannot proceed down the glycolytic pathway and is therefore
accumulated in malignant tissue. This technique has
improved markedly over the past decade, and many centers
routinely incorporate PET imaging results in the staging of
patients with liver metastases, especially when consideration
is being given for liver resection.
Most studies have focused on the diagnostic yield of fluorodeoxyglucose (FDG)-PET in patients with liver metastases
from colon and rectal cancer. The two main limitations of
PET are the lack of anatomical landmarks and poor spatial

resolution. Development of PET/CT has overcome these


drawbacks; unfortunately, most PET/CT examinations are
performed with unenhanced CT images. Recently, some
authors have investigated the role of IV iodinated contrast
material in the evaluation of liver metastases at [18F]FDG
PET/CT (17). They have shown that more liver metastases
were detected on PET/contrast-enhanced CT compared with
PET/unenhanced CT (83% and 67%, respectively). Similarly,
liver metastases were more accurately characterized at PET/
contrast-enhanced CT compared with PET/unenhanced CT
(73% and 57%, respectively).

(A)

(B)

(C)

(D)

Figure 12.4 (AD) MR imaging of endocrine metastases. The tumors are strongly hyperintense on T2- and hypointense on T1-weighted imaging (A and B). Note
the strong hypervascularity on arterial-phase T1-weighted imaging and the washout on portal-phase imaging (C and D).

(A)

(B)

Figure 12.5 MR imaging of liver metastases. Multiple tumors are seen on T2-weighted imaging (A). Conspicuity of small tumors is more evident on diffusionweighted imaging (B).

112

LIVER METASTASES: DETECTION AND IMAGING

perfusion imaging
Liver metastases induce changes in liver perfusion and have
been shown to increase arterial blood flow and the arterial
portal flow ratio (hepatic perfusion index) compared to normal liver. Interestingly, animal studies have demonstrated that
those changes may be detected at an early stage when liver
metastases are occult on other imaging modalities (18).
Hepatic perfusion index can be obtained using various techniques: nuclear medicine, US, CT, or MR imaging. Early results
in patients were promising but lack of standardization in utilization, lack of consensus regarding the imaging modality, and
the presence of multiple mathematical models have meant
that perfusion has not been adopted in routine practice.

other imaging findings


Hypervascular Metastases
Liver metastases from colon carcinoma, other gastrointestinal carcinoma, and pulmonary carcinoma are considered
hypovascular, and those from thyroid carcinoma, neuroendocrine tumor, and renal cell carcinoma are hypervascular
(12) (Fig. 12.5). Breast carcinoma metastases can be either
hypovascular or hypervascular. Furthermore, in Danets
series, patients with metastases that exhibit the nonclassical
type of enhancement according to the primary tumor were
not uncommon. For example, 9% of patients with colon carcinoma had hypervascular metastases (12). This observation
emphasizes the role of imaging in characterizing liver lesions
in cancer patients, and the importance of multiple complementary examinations.
Cystic Metastases
Liver metastases may have a cystic appearance with strong
hyperintensity on heavily T2-weighted MR images. However,
these tumors usually have other findings that are not seen in
typical hepatic cysts such as internal septations, thick walls,
and wall enhancement. Most cystic liver metastases arise from
cystadenocarcinoma, neuroendocrine tumor, and sarcoma.
Calcified Metastases
Up to 11% of patients with colon carcinoma have calcified
liver metastases at presentation. Patients may also develop

(A)

calcification during response to chemotherapy (19) (Fig. 12.6).


Whether liver metastatic calcification carries a prognostic
significance in CRC is still questionable.
Intrabiliary Metastases
Intrinsic bile duct involvement by metastases may occur either
by growing from within or invading the lumen of the bile
ducts. The most common intrabiliary metastases arise from
colorectal carcinoma. Most patients present with various
degree of biliary obstruction including jaundice (20). The
presence of macroscopic intrabiliary extension seems to be a
good indicator in patients with CRC showing less aggressive
features (21).
Pitfalls and Limitations
The two most difficult situations in oncological patients are
the changes in the liver such as steatosis that can create pseudolesions or hide true metastases, and the characterization of
small lesions.
Steatosis is not always homogeneous and may have either
focal fatty sparing, or more rarely focal fatty deposit. Furthermore, fatty livers are often observed in cancer patients who
have received chemotherapy. Clearly, in this context, MR is
superior to CT by combining fat-suppressed T1 sequences and
in- and opposed-phase T1-weighted imaging that can diagnose both focal and diffuse changes, and help to differentiate
focal fat from metastases (Fig. 12.7).
Another issue is the characterization of small liver lesions in
cancer patients. Those lesions (smaller than 1 or 2 cm) are
often deemed too small to characterize, and due to the high
prevalence of benign lesions in the liver, are more frequently
benign than malignant. Schwartz et al. reported in a series of
2978 cancer patients that metastases represented only 11.6%
of patients with small liver lesions (22). Other authors have
shown that the positive predictive value for malignancy
increased notably using a cut-off of 20 mm compared to
10 mm (23). Yet, for an individual patient, we cannot rely only
on lesion size for characterization. While CT is an excellent
imaging modality for detection, it is not as good as US, contrast-enhanced US, and MR imaging when characterizing
small liver lesions (24,25).

(B)

Figure 12.6 (A and B) Liver metastases before and after chemotherapy. Note the significant decrease in size of the tumors. Furthermore, the tumors present diffuse
calcifications after chemotherapy.

113

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

(A)

(B)

(C)

Figure 12.7 (AC) Liver metastases developed on a fatty liver. The tumor located in the posterior part of the segment 4 is barely visible on portal-phase CT (A) and
is better seen on pre- and postcontrast T1-weighted imaging (B and C).

detection of liver metastases:


which imaging modality?
Many different noninvasive imaging modalities are available
for the preoperative detection of liver metastases: US and
contrast-enhanced US, multidetector CT, MR imaging, and
PET using FDG. Comparison of these imaging techniques is
challenging and results have evolved over time due to technological improvements. Multidetector CT has notably
increased the performance of CT in decreasing slice thickness and optimizing lesion enhancement on multiphasic
studies after intravenous contrast. The use of liver-specific
contrast agents in MR imaging has given new horizons for
this imaging modality. Diffusion-weighted MR has markedly
improved the detection of liver metastases. The use of US
contrast agents has completely changed the role of US in
oncology. Integrated PET/CT scanners combining metabolic
and anatomical information has also resulted in an increased
interest in PET studies, and it is likely that the role of IV
iodinated contrast material in PET/CT scanners will be quite
significant. Consequently, many studies have assessed and
compared the diagnostic value of these imaging techniques,
resulting in an extensive body of literature and the absence of
any consensus on the diagnostic algorithm (26). Two systematic reviews (27,28) and one narrative review (29) have analyzed the available evidence (Tables 12.1 and 12.2).
The first systematic review was published by Kinkel et al. in
2002, and aimed at comparing current noninvasive imaging
methods such as US, CT, MR imaging, and FDG PET for the
detection of hepatic metastases from colorectal, gastric, and
esophageal cancers (28). Papers published between December
1985 and December 2000 were studied. Among the 54 studies
included, 9 assessed US (686 patients, 74% with CRC), 25
assessed CT (1747 patients, 78% with CRC), 11 addressed MRI
(401 patients, 100% with CRC), and 9 reported on PET
(423 patients, 100% with CRC). In a per-patient meta-analysis, the authors concluded that [18F]FDG PET was the most
sensitive examination (Level of evidence II): the combined
per-patient sensitivity of [18F]FDG PET (0.90, 95% CI 0.82
0.96) being significantly superior to that of US (0.66, 95% CI
0.540.77), CT (0.70, 95% CI 0.630.77), and MRI (0.71, 95%

114

Table 12.1 Levels of Evidence for Studies of Diagnostic


Test Accuracy
Ia: Systematic review (with homogeneity)* of level-1 studies
Ib: Level 1 studies
II: Level 2 studies or systematic reviews of level-2 studies
III: Level 3 studies or systematic reviews of level-3 studies
IV: Expert committee reports or opinions
Level 1 studies are studies that use a blind comparison of the test
withw a validated reference standard (gold standard)
In a sample of patients that reflects the population to whom the
test would apply
Level 2 studies are studies that have only one of the following:
Narrow population (the sample does not reflect the population to
whom the test would apply)
Use a poor reference standard (defined as that where the test is
included in the reference or where the testing affects the
reference)
The comparison between the test and reference is not blind
Casecontrol studies
Level 3 studies are studies that have at least two or three of the
features listed above
*Homogeneity means there are no or minor variations in the directions and
degrees of results between individual studies that are included in the systematic review.

Table 12.2 Grading of Recommendations on


Diagnostic Tests
Grade A: Studies with level of evidence Ia or Ib
Grade B: Studies with level of evidence II
Grade C: Studies with level of evidence III
Grade D: Studies with level of evidence IV

CI 0.610.80). Moreover, in the 35 studies with specificity


higher than 85%, [18F]FDG PET was still the most sensitive
technique, the combined sensitivity being 55% for US, 72%
for CT, 76% for MR imaging, and 90% for FDG PET.
The second systematic review was published by Bipat et al.
in 2005 and aimed at evaluating CT, MR imaging, and [18F]

LIVER METASTASES: DETECTION AND IMAGING


FDG PET for the detection of colorectal liver metastases on a
per-patient and per-lesion bases, reviewing articles from
1990 to 2003 (27). Among the 61 selected studies, 28 assessed
nonhelical CT, 15 assessed helical CT, 5 concerned 1.0T MRI,
12 concerned 1.5T MRI, and 21 addressed [18F]FDG PET. On
a per-patient basis, the combined sensitivity of PET (0.95,
95% CI 0.930.96) was significantly superior to that of nonhelical CT (0.60, 95% CI 0.580.65), helical CT (0.65, 95%
CI 0.300.89), and 1.5T MRI (0.76, 95% CI 0.560.89) (Level
of evidence II). On a perlesion basis, nonhelical CT sensitivity (0.52, 95% CI 0.520.53) was significantly lower than
that of helical CT (0.64, 95% CI 0.540.72), 1.0T MRI (0.66,
95% CI 0.660.66), 1.5T MRI (0.64, 95% CI 0.580.71), and
PET (0.76, 95% CI 0.610.86). In other words, there was no
evidence that the per-lesion sensitivities of PET, helical
CT, and MRI differed significantly. For lesions of 1 cm or
larger, SPIO-enhanced MR imaging was the most accurate
modality.
Therefore, considerable debate continues about which imaging modality offers the best noninvasive examination of the
liver, and so some comments concerning the existing evidence
need to be addressed.
First, the diagnostic value of imaging techniques can be
computed per patient (detection of at least one lesion per
patient) or per lesion (detection of all lesions per patient). But,
in cancer patients, the per-patient analysis is not adequate
because the main question is not: Does the patient have liver
metastases? But rather, How many metastases are in the liver,
and where? As previously seen in the results of the prior metaanalyses, the per-lesion comparison of imaging modalities is
still open.
The second point worth considering is the frequent use of a
suboptimal diagnostic reference standard. The most reliable
reference standard is the combination of direct visualization
and bimanual palpation of the liver, intraoperative US, and
histopathological examination of resected liver tissue of each
lesion found in the liver, so allowing for a lesion-by-lesion
analysis. But only a minority of studies used this reference
standard, resulting in underdetection of lesions and overestimation of sensitivity. Studies that analyzed the detection of
liver metastases without this surgical reference standard (that
is using imaging follow-up or a combination of other imaging
modalities) are of limited value because sensitivity of the
methodology will appear higher than the true one. It should
be noted that even with this extensive pre- and intraoperative
workup, lesions may be missed and in two series approximately 15% of patients were found to have new tumors on
follow-up CT scans performed four to six months after hepatic
resection (30,31).
Third, the imaging modalities analyzed in the two metaanalyses extended for a long period of time from 1985 or
1990 to 2000 and their results are difficult to compare with
up-to-date imaging. Research on hepatic contrast agents
has advanced in two directions: first the development of
US contrast agent, especially the more stable second generation of contrast media, has prompted a revival of interest in contrast-enhanced US; second tissue-specific MR
contrast agents have been developed to target the main cell

populations of the liver. These advances, as well as those of


multidetector-row CT (32 or 64 slice systems) or PET/CT,
were not integrated in the two available systematic reviews
but were discussed in the Rappeport and Loft narrative
review (29).
Considering the available comparisons of modern MR
imaging, multidetector-row CT and PET in the same group of
patients with surgical reference standards, Rappeport and Loft
questioned the conclusions of the two prior systematic reviews.
The authors concluded that state-of the-art anatomical imaging, e.g., liver-specific MR imaging and multidetector CT,
must be considered more sensitive than PET in the detection
of individual liver metastases (Level of evidence II) (29). They
also stated that a preoperative PET/CT-study for detection of
possible extra-hepatic tumor contraindicating liver surgery is
also recommended. Moreover, recent articles have pointed
out the limitation of FDG-PET in detecting small liver
metastases, with a significant superiority of CT and MR
imaging (3234). This is a key result because most lesions
larger than 1 cm are depicted on all imaging techniques, but
the detection of subcentimeter metastases remains disappointing and therefore the comparison of imaging modalities
should focus on these small lesions.
Consequently, the question seems to be which is the better
imaging modality between CT and MR? And should we use
nonspecific MR contrast or liver-specific contrast agents? We
have to take into consideration the following:

Multidetector-row CT scanning is often the first


choice for a screening liver examination at many
institutions. This technique also enables rapid scanning of the chest and abdomen and allows evaluation
of extrahepatic disease.
MRI enhanced with SPIO is probably a more sensitive method than multidetector-row CT for detecting liver metastases (35,36), but to our knowledge,
no study has evaluated the added value of MR imaging after multidetector-row CT examination and the
consequences in treatment planning.

Based on the existing evidence, it is difficult to provide highstrength management recommendations. Our policy at our
institution is to perform systematically a multidetector CT in
patients with liver metastases. PET/CT is indicated for the
detection of extrahepatic tumor before liver surgery. MR
imaging is not routinely performed and is reserved for characterization of small liver lesions, in fatty livers, and in difficult
cases after multidetector CT. For lesion characterization, we
use nonspecific contrast MR agents, while for tumor detection
and preoperative staging, we use liver-specific contrast agents.
In both cases, our protocol includes diffusion-weighted MR
sequences. Intraoperative US is routinely performed in our
institution and intraoperative contrast-enhanced US is under
investigation.

preoperative staging
Due to their biological properties, most liver metastases that
are resected are secondary to CRC. Selected isolated liver
metastases from breast cancer, sarcoma, renal cell cancer

115

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


and Wilms tumors, melanoma, other GI cancers, and, most
frequently, endocrine tumors, may benefit from liver
resection (5).
Assessment of the number and location of liver metastases is
a major issue of preoperative staging and has been described
previously. Yet, imaging has to answer other questions relevant
to technical success and R0 resection:

Does the future liver remnant have sufficient volume


for the perioperative and postoperative course? This
question is easily addressed by CT or MR volumetric
measurement.
Does the future liver remnant have satisfactory vascular inflow, venous outflow, and biliary drainage?
Again CT or MR imaging is adequate to answer this
question.
Is there any contraindication to performing an R0
resection? This point is more difficult as classical
contraindications such as bilobar metastases are
overcome in most specialized centers either by twostep resection with preoperative portal embolization
to increase the remaining normal liver parenchyma
or downsizing with chemotherapy, or combination
of resection and thermal ablation (37). However, it is
crucial to evaluate the relationship between the liver
tumors and important anatomical landmarks such
as the inferior vena cava (IVC), hepatic venous confluence, and the main portal pedicles.
Did the liver metastases respond to preoperative chemotherapy? Preoperative chemotherapy is currently
performed in resectable patients as it has been shown
to reduce the risk of events of progression-free
survival in eligible and resected patients (38). In
these patients, the role of imaging is to evaluate
the tumor response according to RECIST (Response
Evaluation Criteria in Solid Tumors) criteria.
Association with targeted therapy may render more
complex this assessment.

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117

13

Surgery for metastatic colorectal cancer


Ren Adam and E. Hoti

introduction
Colorectal cancer (CRC) is a common malignancy with a very
high incidence in Western countries. Approximately 150,000
new cases of CRC occur each year in the United States,
accounting for more than 55,000 cancer-related deaths (1).
Over half the patients diagnosed with CRC will develop liver
metastases (CRLM) during the course of their disease (2), of
which 15% to 25% will have liver metastases at the time of the
diagnosis (3,4). In the absence of surgical treatment, 5-year
survival is exceptional (5) and even with the best chemo- and
bio-therapies, to date, median survival of unresected disease
does not exceed two years (6,7). On the other hand, long-term
survival and potential cure after surgical resection for CRLM
has been demonstrated by numerous studies. Surgery is therefore considered as the treatment of choice for patients with
resectable CRLM, yielding a 5-year survival between 35% and
52% (8,9). As a result, hepatic resection has evolved from a
rare procedure associated with considerable mortality to a
routine surgery with an operative mortality risk of around 2%
(10,11). At present, the low operative mortality along with survival improvement has led to an expansion of more extensive
liver surgery and to a clear change in surgical indications to a
point where virtually no tumor should be considered unresectable provided that resection can be complete. These
advances combined with novel systemic and regional ablative
therapies have modified the course of the disease, transforming it from a uniformly fatal to increasingly curable for a
majority of patients.

natural history of colorectal liver


metastases
The natural history of untreated CRLM has been well studied.
The median survival untreated following diagnosis is 6 to
12 months and 5-year survival is extremely rare. Most studies
indicate that the prognosis is most closely related to tumor
burden. Wood et al. showed that while the 1-year survival was
only 5.7% for patients with widespread disease, 60% of the
patients with solitary liver metastases were alive at 1 year with
a mean survival of 25 months (12). Wagner et al. (5) reported
the 3- and 5-year survival for untreated resectable disease to be
14% and 2%, compared to 4% and 0% for unresectable disease. Wilson and Adson (13) in their case-controlled study
(60 patients treated with hepatic resection versus 60 comparable patients not subjected to surgery) demonstrated that
hepatic resection was associated with 5-, 10- year survival of
25% and 19% compared to no 5-year survival in the non
resectable group. Two other case-control studies demonstrated
almost identical results (5,14). Scheele et al. (14) reported a
5-year survival rate 40% in patients who underwent tumor
resections compared to 0% in 62 patients who had potentially
resectable tumors but did not undergo resection.

118

Although long-term survival and potential cure after surgical resection has not been demonstrated by randomized controlled trials, the evidence (uniformly poor results observed in
untreated patients in contrast to extensive data documenting
long-term survival after hepatectomy) supports a significant
survival benefit from resection and has provided the rationale
for increasing indications for liver surgery as the most effective
treatment of CRLM.

patient evaluation
Patient Selection for Surgery
In deciding which patient will tolerate liver resection, a number of factors will need to be considered, including patient
comorbidities. Age per se is not an independent factor for
increased operative risk (15). This is a very important fact,
considering that an increasing proportion of patients being
evaluated for surgery for malignant disease, are elderly. On the
other hand, scores like the American Society of Anaesthesiology (ASA) (16) or the preoperative Acute Physiology and
Chronic Health Evaluation score do significantly influence the
incidence of postoperative complications. Patients with an
ASA score > 1 have been shown to have more than three times
the mortality and twice the morbidity compared to those
patients with an ASA of 1 (16). Therefore, a major goal of the
preoperative evaluation is to identify patients who are at high
operative risk so those who have a prohibitive risk can be
excluded from surgery whereas those with manageable comorbidities can have these conditions addressed preoperatively in
an attempt to reduce their operative risk.
Definition of Tumor Resectability
The earlier definition of the resectability (based on factors
such as number of lesions, size, distribution, etc.) has been
progressively challenged resulting on a concept shift, which
now focuses on whether a macroscopic and microscopic complete (R0) resection of the liver lesion as well as complete
resection of any extrahepatic diseases can be performed. At
present, CRLM are defined as resectable if two aspects are fulfilled: (1) oncological anticipation that the disease can be completely resected without any residual hepatic or extrahepatic
disease; (2) maintenance of an adequate volume of the future
remnant liver with preserved vascular inflow, outflow, and
biliary drainage. In general, at least 25% of the total liver is the
minimum safe volume that can be left after liver resection in
patients with normal liver parenchyma (17).
Preoperative Imaging
The complex decision to determine resectability requires
detailed anatomic imaging to determine tumor location,
exclude unresectable extrahepatic metastases, and assess the
adequacy of the liver parenchyma after surgery. There are a

SURGERY FOR METASTATIC COLORECTAL CANCER


myriad of diagnostic capabilities available to date, including
three-dimensional CT scanning, CT angiography, magnetic
resonance angiography (MRI), and CT volumetry. Nevertheless, despite the evolution of imaging modalities, difficulties
still exist, especially when trying to differentiate between
metastases and benign liver lesions or to detect small metastatic lesions. The current approach to address these pitfalls is
to use a multimodality strategy (18). For example, although
helical CT scanning provides information for the entire chest
and abdomen during a single breath hold, up to 25% of the
lesion can still be missed (19). MRI, on the other hand, is currently the most effective imaging modality in detecting and
characterizing liver lesions and is often ordered prior to liver
resection to characterize indeterminate lesions seen on a CT
scan as it has a higher sensitivity to detect and characterize
small lesions (20). Using liver-specific contrast agents, MRI
has equivalent sensitivity to CT angiography (21) (Level of
evidence: 1). Positron emission tomography (PET) is another
useful modality for detecting liver metastases, especially when
combined with CT scann. However, it is no more sensitive
than MRI in detection, and it lacks the special resolution and
the ability to characterize lesions. Truant et al. (22) correlated
PET and CT findings in 53 patients with final pathologic diagnoses. They found that PET detected significantly more extrahepatic, intraperitoneal metastases than CT, with a sensitivity
of 63% versus 25%. Another meta-analysis study, comparing
helical CT, MRI, and fluorodeoxy-glucose PET (FDG-PET) in
the detection of colorectal liver metastases, showed that the
sensitivities on a per-patient basis were 64.7%, 78.8%, and
94.6%, respectively (23). In contrast, there are other reports
that have questioned the superiority of the FDG-PET and consider MRI and helical CT more sensitive in detecting small
liver metastases (24,25). PET and FDG-PET are, however,
more advantageous in identifying extrahepatic and possible
unresectable metastases, which could be a contraindication to
liver resection (26) (Level of evidence 1). In addition, the ability of the later investigation to detect occult disease prevents
unnecessary surgery in 21.5% of patients and changes the
overall management in 25% (26). Hence, despite their pitfalls,
the use of image overlays, combining FDG-PET and helical CT
or MRI, can increase the accuracy of preoperative staging
before hepatic resection (27) (Level of evidence: 1).

prognostic factors and clinical risk scores


Prognostic Factors
The importance of prognostic factors lies in two aspects: evaluation of the prognosis and selection of candidates for surgery.
With the evolution, some accepted negative prognostic factors
are no more considered, while new ones appear as substitutes.
Factors that have been consistently considered as absolute or
relative contraindications to liver resection are number/location of liver metastases, resection margin, presence of extrahepatic disease, and tumor involvement of portal lymph nodes.

The number of metastases (4) is no longer considered


a contraindication (28) to liver resection (based on the
fact that long-term survival can be obtained for
patients with four or more metastases treated with

surgery). When resecting 4 liver metastases, the limiting factor is not the number of metastases but
whether it is possible to remove all of them (2932).
Similarly, the distribution (bilobar metastatic disease)
is no longer considered as a prohibitive prognostic
factor. Ercolani et al. (33) reported that the total tumor
volume of liver metastases had a stronger influence on
survival than did number and location. Also, data
from LiverMetSurvey concerning patients with bilobar metastatic disease have demonstrated a 1-, 5-, and
10-year survival of 90%, 44%, and 22%, respectively
(34). In general, if a complete resection of the metastases can be achieved with safe margins (R0 resection)
while maintaining a sufficient volume of the residual
liver, the number and location should not be considered as a contraindication to resection.
Whereas achieving a negative resection margin is well
established, the extent of this margin clearance
remains controversial. Increasingly, studies are demonstrating that there is no significant difference in
survival or recurrence related to the width of margin
achieved. Elias et al. (35) demonstrated that the overall survival of patients with resection margins less
than 1 cm was 27.8%, comparable to those with resection margins of 1 cm. Fong et al. (36), in his series of
426 patients undergoing hepatectomy for CRLM,
reported an identical 5-year survival in the group
with a clear margin of <1 cm compared to the group
with a margin of 1 cm or greater. Similarly, Figueras
et al. (37) reported that subcentimeter nonpositive
surgical margin did not influence hepatic recurrence
rates after hepatectomy for CLM. Kokudo et al. (38),
in his study, went further on by demonstrating that a
margin of 2 mm is clinically the minimum acceptable
requirement, which carries approximately a 6% risk of
margin-related recurrence. A recently published study
from our center showed that despite a higher recurrence rate in patients with R1 resection (complete macroscopic resection with 0 mm free margin) compared
to patients with R0 resection, the two groups had a
similar overall and disease-free survival (61% vs. 57%
and 28% vs. 17%) and recurrences were intrahepatic
rather than being localized at the surgical margin (39).

Therefore, the absence of safe margins of resection should


not be considered as an absolute contraindication to surgery
provided that all tumors can be macroscopically resected.
However, at the present surgeons should continue to plan
hepatic resection with a preserved safety zone and avoid routine use of minimum margin surgery.

The presence of extrahepatic disease reduces the


hope of long-term survival and it has been considered as a contraindication to liver resection. Lately,
however, resection in patients with extrahepatic
disease with curative intent has been advocated by
some groups. In a French series (40) of 84 patients
who underwent complete resection of extrahepatic
disease concurrently with hepatic resection, the

119

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS

overall 5-year survival was 28% compared to 34% in


the 224 patients undergoing liver resection alone. In
addition, the study demonstrated that the total number of metastases has a stronger negative prognostic
value after complete resection than their location.
Other reports have suggested that patients with
extrahepatic metastases may survive more than
5 years after a successful liver resection (41) (Level of
evidence: 3). Encouraging results have been reported
even after combined resection of concomitant liver
metastases and peritoneal carcinomatosis, which has
been traditionally considered as an absolute contraindication to liver resection (42,43). However, these
results are observed in patients with a limited number of liver metastases (3 lesions).
Involvement of the portal lymph nodes may be present
in as many as 14% of patients with CRLM (44). Some
authors have suggested that radical excision of involved
portal nodes can produce a survival benefit (45). In a
prospective study conducted by Jaeck et al. (46), the
survival rate in patients with involved portal lymph
nodes was significantly lower than in the control group
(3-year survival 19% vs. 62%). However, patients with
involved lymph nodes limited to the hepatoduodenal
ligament and retropancreatic portion demonstrated a
much better prognosis than those with involved lymph
nodes around the common hepatic artery and celiac
axis (3-year survival 38% vs. 0%). In a more recent
study (47) conducted in patients responding to preoperative chemotherapy, we reported that combining
liver resection and pedicular lymphadenopathy was
justified in patients with involved pedicular lymph
nodes (3- and 5-year survival 38% and 18%, respectively). Conversely, in patients with involved celiac or
retroperitoneal lymph nodes, this approach was not
justified (5-year survival 0%). In this group of patients,
even the response to chemotherapy did not seem to
change their usual poor prognosis.

is the impossibility to remove all metastatic disease, while leaving sufficient functional hepatic parenchyma, regardless of the
location, distribution, number and size of the metastases.
Clinical Risk Scores
Over 10 years ago, Nordlinger (48) introduced the first scoring
system for patients with CRLM, based on a multicenter data
from 1568 patients who accepted potentially curative resections. In this large series, they identified three groups of
patients with low, intermediate and high risk for poor prognosis based on seven high risk factors (see Table 13.1A). Since
then, at least six more scoring systems have been developed
among which the proposal from Fong et al. (49) based on a
single institution series of 1001 patients attracted the most
attention. Seven parameters were found to be independent
predictors of prognosis. These include presence of extrahepatic disease; positive resection margin; nodal metastases
from primary cancer; short disease free interval; largest tumor
greater than 5 cm; more than 1 liver metastases; CEA greater
than 200 ng/ml (see Table 13.1A). The data for the first two
parameters are not available preoperatively. However, using
the last five criteria, a preoperative clinical risk score system
was created with each positive criterion counting as 1 point.
The total score out of 5 is highly predictive of a poor outcome
(5-year survival 14%). Patients with a score of 0, 1, and 2 have
a highly favorable outcome (5-year survival 60%, 44%, and
40%, respectively). Table 13.1B demonstrates the survival
rates for each score grade.

Table 13.1A Prognostic Scoring Systems


Fongs score*

Whereas preoperative factors may be generally instructive,


these should not be used to exclude patients from surgical consideration. Patients with one or multiple negative prognostic
factors can still derive a significant survival advantage from
hepatic resection of their CRLM.
To conclude, it is important to mention that at the present
time the only unchallenged contraindication to liver resection

Nordlingers score*

Node-positive primary tumor Stage of the primary tumor


Disease-free interval
Disease free interval (2 years vs.
(<12 months between colon
<2 years)
resection and appearance of
metastases)
Size of largest lesion >5 cm
Size of the largest metastasis
(<5 cm vs. 5 cm)
More than 1 tumor
Number of liver nodules (13 vs.
4 or more)
CEA >200 ng/mL
Resection margin (>1cm vs.
<1 cm)
Age (<60 years vs. 60 years
*One point is assigned for each risk factor

Table 13.1B Survival Rates for Each Score Grade


Survival (%)
Fongs score
Score
0
1
2
3
4
5

120

Nordlingers score

1 year

3 years

5 years

Median (mo)

93
91
89
86
70
71

72
66
60
42
38
27

60
44
40
20
25
14

74
51
47
33
20
22

Risk groups

Risk factors

2 years

Low risk

02

79

Intermediate risk

34

60

High risk

57

43

SURGERY FOR METASTATIC COLORECTAL CANCER


The applicability of this score has been evaluated by independent investigators from Norway (50), indicating that the
score is applicable to other populations outside of a large
tertiary U.S. center. Recent data from Asia has shown that CRS
is useful for predicting outcome after ablative therapy of liver
metastases. Also the CRS can help to select the extent and
sophistication of preoperative assessment (51) acting as a risk
stratification tool in identifying patients who are most and
least likely to have their management altered by the results of
the test.
In practice, although the scores are simple, easy to use and
highly predictive of long-term outcome their clinical relevance
in terms of indications and contraindications to surgery is low
since even with poor prognostic factors, hepatic resection can
provide a chance of long-term survival. Patients with poor
scores could, however, be selected more appropriately for neoadjuvant and adjuvant therapy or for refined preoperative
imaging (routine PET CT) to exclude those with contraindications to surgery. In addition, scores have proved useful for
comparing results from different centers for surgical and ablative therapies as well as stratification of patients for trials.

after the surgery (58). The preoperative cycles induced a complete response in 3.8% of patients and a partial response in
40.1% with a decrease in the diameter of the nodules of 29.5%.
At 3 years, the disease-free survival was 28.1% in the group
treated with surgery alone and 35.4% in the group that received
perioperative chemotherapy (p = 0.058). The reduction of the
size of the nodules could modify and facilitate the liver resection
with a minor hepatectomy instead of a major liver resection.
In patients presenting with five or more bilobar metastases,
Tanaka et al. (59) showed that the 5-year survival rate was 38.9%
in the group receiving neoadjuvant chemotherapy compared to
20.7% of the group treated with hepatectomy alone. In addition, multivariate analysis revealed neoadjuvant chemotherapy
to be an independent predictive factor for survival. These results
suggest a survival benefit of neoadjuvant chemotherapy in
patients with resectable metastases. Whether the use of adjuvant chemotherapy would translate as the gold standard practice is still a matter of debate. Obviously, multinodular
metastases are very likely to benefit from neoadjuvant chemotherapy owing to the potential of missing small metastases.

management of patients with resectable


colorectal liver metastases

Approaches to Surgery
Assessment of Functional Hepatic Reserve
The functional hepatic reserve can be assessed by ChildPugh
score and hepatic biological blood tests, however, to date the
only test which has proven to have a good predictive value is
the indocyanine green (ICG) clearance test (60). In candidates
for liver resection with retention of less than 20% of ICG at
15 minutes, up to 60% of the volume of the parenchyma can
be resected. Although liver metastases rarely develop in cirrhotic liver, with the ever increasing use of more efficient chemotherapy regimens and targeted agents, a rising number of
patients are expected to present with damaged livers as a result
of chemotherapy given before resection. Specific pathologic
changes of the liver parenchyma (vascular changes and/or chemotherapy associated steatohepatitis) influencing the liver
regeneration and function as well as the ability of the patient
to recover have been observed, following administration of
preoperative chemotherapy. Hence in this new context, evaluation of the functional reserve of the liver is becoming critical.

Preoperative management
Neoadjuvant Chemotherapy
Conventional first-line chemotherapeutic regimens for resectable colorectal liver metastases (CRLM) contain fluorouracil
(5-FU) in addition to leucovorin. Using a bolus administration regimen for patients treated with 5-FU and leucovorin
response rates ranging from 20% to 30% and a median survival of 11.5 months has been reported (52,53). No significant
difference in median survival has been observed when the
5-FU was delivered by continuous infusion, despite improvement of the response rate and reduction of the toxicity.
Combination of 5-FU with newer drugs such as irinotecan
(topoisomerase I inhibitor) resulted in a higher response rate
(39%), longer progression free and overall survival time
(14.8) compared to 5-FU and leucovorin alone (54). In addition, it has been shown that irinotecan in combination with
continuous infusion of 5-FU/ leucovorin (FOLFIRI) produces
better response rates and longer progression free and overall
survival compared to 5-FU/leucovorin alone (55). More
recently, the combination of infusional 5-FU/leucovorin with
oxaliplatin (cisplatin derivative) has been found to be less
toxic and more efficacious than the bolus irinotecan/5-FU/
leucovorin regimen (56,57). Whether the combination of
infusional 5-FU/leucovorin with oxaliplatin (FOLFOX) or
FOLFIRI is better as first-line chemotherapy remains controversial as they have comparable response rates. What may be
more persuasive is that when these regimens are used sequentially when progression or toxicity occurs, regardless the order,
survival is prolonged.
For patients with up to four liver metastases, a prospective
trial conducted by the European Organization for the Research
and Treatment of Cancer compared surgery alone versus
surgery with perioperative chemotherapy (FOLFOX
4 oxaliplatin/5-FU/leucovorin), six cycles before and six cycles

Preoperative Biopsies
Currently routine biopsy of liver lesions as part of the diagnostic process for patients who are thought to have potentially
resectable lesions is not recommended. Although the seeding
along the needle track has been believed to be very rare (incidence 0.0030.07%) (61,62), it appears that it has been greatly
underestimated. An incidence of needle track metastases ranging from 10% to 19% has recently been reported (63,64).
Therefore, the potential benefits of liver biopsy in suspected
patients are outweighted by the risk of these serious complications as well as the risk of deriving false reassurance from a
false-negative result.
Role of Laparoscopy and Laparoscopic Ultrasound (LUS)
Evaluation
In the recent years, many surgeons have advocated the use of
laparoscopy for evaluation of CRLM preoperatively in order to

121

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


reduce the number of unnecessary surgical explorations. This
procedure has been reported to exclude 25% to 48% of patients
from laparotomy with a false-negative rate of less than 15%
(65,66). Grobmyer et al. (67) suggested that patients should be
considered for laparoscopic evaluation if they have two of the
following characteristics: lymph node positive primary tumor,
CEA levels greater than 200 ng/mL, >1 hepatic lesion, diseasefree interval <12 months, and hepatic metastatic lesion >5 cm.
Patients with two or more of these factors have a 30% chance of
having occult extrahepatic disease. However, with increasingly
sensitive preoperative imaging and the increasing use of ablation and resection of extrahepatic sites, fewer patients are subjected to nontherapeutic laparoscopy (Level of evidence: 3).
Role of Intraoperative Ultrasound (IOUS)
IOUS is an essential adjunct to conventional imaging and is
widely used to guide surgery and ablative techniques. In experienced hands, IOUS has been shown to contribute to acquisition of precise details regarding tumor size, location, extent of
local invasion, and may alter or guide the surgery in up to 67%
of cases (68). Also, when compared with preoperative radiological findings, IOUS has been found to be able to identify at
least one additional malignant lesion in 10% to 12% of cases
(6870). As such, the use of IOUS should be considered as
mandatory not only for intraoperative diagnostics but also for
determining the type of surgical procedure (resection).
Types of Liver Resection
Generally liver resection can be divided into two groups: anatomic (resection of one or several segments) and nonanatomic
wedge resections (resection of a portion of parenchyma surrounding the metastatic lesion). If more than three segments
are resected, the hepatectomy is defined as major. Different
types of anatomic liver resection are performed: right hepatectomy (segments VVIII), left lateral lobectomy (segments II,
III), and left hepatectomy (segments IIIV). Other types
include central resection (segments IV, V, VIII) and bisegmentectomies (segments V, VI or segments IV, V). Resections
exceeding the boundaries of a normal right or left are defined
as extended hepatic resections and are divided in six different
types. Right hepatectomies extended to segment IV, segment I,
or both. Similarly, extended left hepatectomies may include
segment I, segments V and VIII, or segments I, V, and VIII.
Selecting the Resection Type
The principles of hepatic resection (including the oncological
goal which is to remove all metastatic sites with tumor free
margins) are no different for colorectal metastases than for
any other hepatic surgery. Rather than dogmatically adhering
to an anatomical versus nonanatomic approach, the hepatobiliary surgeons now guide their decisions aiming ultimately at
resecting all metastases with negative histologic margins.
Therefore, the type of resection chosen for a particular patient
is and should be individualized based on the size, number, and
location of the metastases, their relation to main vascular pedicles, and the volume of future liver parenchyma. Whereas a
small, superficial metastasis can be best treated with a nonanatomic resection, a large metastasis deeply located within the

122

Figure 13.1 Picture showing multiple metastasectomies with maximal preservation of the liver parenchyma.

liver may be treated with an anatomical, segment-oriented


resection. The extent of liver resection (major vs. minor or
anatomic vs. nonanatomic resection) is not by itself a prognostic factor. Therefore, independently of being anatomic or
nonanatomic, resection should spare as much as possible the
nontumoral parenchyma, bearing in mind that new recurrences could eventually develop for which surgery could possibly be indicated again (see Fig. 13.1).

postoperative management
Adjuvant Systemic Chemotherapy
At present, despite several chemotherapy regimens, data would
support the use of 5-FU and leucovorin as adjuvant chemotherapy after liver resection if patients have not previously
failed this regimen. Portier et al., in a multicenter trial that randomized 173 patients after hepatectomy for CRLM to surgery
alone or to surgery followed by chemotherapy (5-FU/ Leucovorin), demonstrated that patients who received adjuvant chemotherapy had a significantly better disease-free survival compared
to that of patients treated with surgery alone (34% vs. 27%; p =
0.03) (71). A year later, Park et al., in a large two-center study
comparing 518 patients treated with no chemotherapy (379
American, 139 European) to 274 patients treated (240 American, 34 European) with 5-FU-based adjuvant chemotherapy,
demonstrated that systemic adjuvant chemotherapy prolongs
survival after hepatic resection for colorectal metastases (72).
Patients subjected to adjuvant chemotherapy had improved
survival (p = 0.007) even after stratification by clinical risk
score (p = 0.001). In every clinical risk score category, patients
subjected to adjuvant chemotherapy had a higher chance of
survival (range 1.32.0 times).
Meanwhile, for those who have previously failed this regimen, an oxaliplatin- or irinotecan-based regimen should
be considered. Despite that there has not been a clear demonstration of efficacy of any regimen, the higher response
rate observed in patients treated with FOLFOX or FOLFIRI
over the 5-FU/leucovorin has resulted in many groups to
preferentially use these regimens in adjuvant settings.

SURGERY FOR METASTATIC COLORECTAL CANCER


Table 13.2 Reported Survival Outcomes after Resection of Colorectal Liver Metastases with Curative Intent
Operative
mortality
(%)

Patient survival (%)

Author

Year

No. of
patients

Postoperative
morbidity (%)

1 year

3 years

5 years

10 years

Nordlinger
et al.
Fong et al.
Minagawa
et al.
Suzuki et al.
Choti et al.
Adam et al.
Kato et al.
Abdalla et al.
Tanaka et al.
Fernandez
et al.
Pawlik et al.
Wei et al.

1995

1568

28

1999
2000

1001
235

2.8
0.8

89

57
51

36
38

22
38

2001
2002
2003
2003
2004
2004
2005

26
226
615
585
190
193
100

1
1
0

18.6
18

26
1

93
91

69
86

62
57
61

73
46
66

32
40
41
33
58
43
58

26

2005
2006

557
423

1
2

19.6

97
93

74

58
47

28

Adjuvant Intra-arterial Chemotherapy


A number of studies have reported the safety, efficacy, and
feasibility of adjuvant regional hepatic chemotherapy.
Kusunoki et al. conducted a nonrandomized trial of HAI
versus systemic chemotherapy after radical liver surgery. He
showed that the 5-year survival was significantly better for
the HAI group compared to the 5-year survival of the systemic group (59% vs. 27%, p < 0.001) (73). Kemeny et al., in
an intergroup study of 109 patients randomized to surgery
alone or surgery and HAI-FUDR, demonstrated that the
4-year disease-free survival was significantly better in the
HAI group (67% vs. 43%) (74). In another larger study,
156 patients were randomized to resection and systemic
5-FU or resection and combined systemic 5-FU and HAIFUDR. The patients who were treated with regional therapy
had a significantly better 2-year survival (86% vs. 72%) and
markedly improved liver disease control (75).
In conclusion, convincing evidence currently exist to support the use of adjuvant chemotherapy, either systemic or
regional, to prevent to some extent the risk of recurrence
following liver resection.
Outcomes of Resection for Colorectal Liver Metastases
Morbidity and Mortality
Overall, the perioperative mortality of liver resection for
CRLM does not exceed 2%, ranging between 0% and 5% in
most published series (10,11,76) and is strongly influenced by
perioperative blood loss, liver function, and extent of liver
resection. In experienced units, even major hepatic resections,
constituting around 50% of cases have perioperative mortality
not exceeding 2% (76). The principal causes of death are liver
failure and sepsis.
It has been observed that the mortality has changed little
over the last two decades, however, this does not mean that
there has not been progress made. With improved safety, surgeons are increasingly performing more extensive resections,

which explain the fact why the operative mortality and longterm survival have plateaued.
In contrast, the perioperative morbidity rate is reported to
be greater than 20% (28,77). The major morbidity associated with liver resection includes hemorrhage (13%), bile
leak and/or fistula (4%), pleural effusion/pneumonia
(510%/520%), and hepatic failure (38%). Of the nonliver-related complications, intra-abdominal sepsis is found
to be the most frequent major complication, and pulmonary
infection is the most frequent minor complication. Among
liver-related complications, liver failure is the most serious
and occurs in 3% to 8% of all major liver resections often
being lethal. Similarly, intraoperative hemorrhage, although
rare, is another major complication with a mortality as high
as 17% (78).
Long-term Survival Results
Large series have reported a 5-year survival after hepatectomy
for CRLM of 35% to 52% with a 33- to 46-month median survival (8,9,46,79) (see Table 13.2). However, recent data have
shown an improved 5-year survival rate of 58% after complete
resection of CRLM (35). Also, a number of series with sufficiently long-term follow-up indicate that the 10-year survival
after resection can be expected in 20% to 30% of patients
(12,46,80) (see Table 13.2 and Fig. 13.1). Similarly the International Registry of Hepatic Metastases of Colorectal Cancer
(LiverMetSurvey), which to date includes more than
8000 patients, has demonstrated a 5- and 10-year survival of
41% and 26%, respectively.
An important oncologic question is whether the recently
improved systemic therapies can achieve the same results as
resection for CRLM? This seems unlikely considering that longterm survival beyond 5-years is rare without liver resection (5)
(Fig. 13.2). Indeed, the survival results can be questioned if
considering that the patients who undergo resection are selected
and may have better outcomes due to less aggressive disease.

123

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


However, there has never been a controlled trial to compare
resection versus nonresection or conservative treatment of
potentially resectable CRLM and this is unlikely to happen in
the near future unless more efficacious systemic therapy regimens are discovered.

(Level of evidence: 3). A study conducted by our group (81)


demonstrated that an additional 16% of patients who had initially unresectable liver metastases became candidates for
hepatic surgery after receiving systemic chemotherapy. The 3and 5-year survival rates were 54% and 40%, respectively,
close to those observed after resection of initially resectable
nodules. These results were confirmed by other studies
including ours (82,83). In 2004, we reported that subsequent
rescue surgery for unresectable CRLM downsized by chemotherapy resulted in a 5- and 10-year survival rate of 33% and
23%, respectively, with a disease-free survival of 17% at
10 years (82) (Figs. 13.3 and 13.4). In contrast, patients with
tumor progression during preoperative chemotherapy have a
significantly worse outcome, with a 5-year survival of 8%
versus 37% and 30% for patients with objective tumor
response or tumor stabilization (84). Patients with tumor
progression still had a poor prognosis even when a potentially curative hepatic resection was performed. Another
aspect worth mentioning about is the combination of chemotherapy with new molecular-targeted drugs (bevacizumab, cetuximab). These agents have had a significant
impact on the survival of patients with advanced CRC disease when integrated with chemotherapy in trials. Using
them in combination with oxaliplatin- or irinotecan-based
regimens, these agents have produced tumor response rates
greater than 50% to 60% (85). Disease control rates (complete response; partial response or stabilization of disease)
exceeded 90% in the report of a phase II study of FOLFOX
combined with cetuximab in nonoperable patients with epidermal growth factor receptor-expressing metastatic CRC
(86). The objective response rate was 79% according to independent expert review (87).
Data from the Paul Brousse series showed that the use of
targeted agents in second line therapy also increases the number of patients eligible for resection. A total of 131 patients
with epidermal growth factor receptor-positive CRLM who
had progressed following two or more lines of FOLFOX or

Management of Nonresectable Metastatic Disease


Despite the advances made so far in liver surgery, approximately 80% to 90% of patients with CRC liver metastases are
not candidates for liver resection at the time of diagnosis.
Apart from the fitness of the patients, the unresectability of
liver lesions is due to the following reasons: technically unable
to completely remove the lesions due to the number, size, and
their distribution; or due to ill location of the metastatic lesion
(infiltration of IVC, confluence of hepatic veins). As the most
frequent cause responsible for technical unresectability is multinodular bilobar metastatic disease, different approaches used
alone or in tailored combinations have been developed to
improve the resectability rate by either reducing the tumor
burden (in turn the extent of the hepatic resection) or by
increasing the volume of remnant liver parenchyma. Instead,
ill-located metastases are being increasingly treated by radical
surgery such as liver resection combined with total vascular
exclusion (TVE).
Chemotherapy to Downstage Nonresectable
Metastatic Disease
Systemic Chemotherapy
The improved efficacy of chemotherapy agents has not only
allowed increased patient survival in the noncurative setting,
but has allowed a subset of previously unresectable patients to
undergo liver surgery after tumor downstaging, a concept
first introduced by our team (81). By reconsidering the initial
unresectability of patients who strongly respond to chemotherapy, several investigators have shown that survival can be
achieved by liver resection in a significant proportion of
patients who otherwise would have had a poor outcome

Patient survival after a 1st liver operation for colorectal metastases: 8179 patients
Log rank p = <0.0001

100
90
80
70
60
50

41%

40

7737 resected patients


26%

30
20
10

442 nonresected patients

7%

0
0

2
Resected

5
Resected

10

Nonresected

Figure 13.2 Five- and ten-year survival following hepatectomy for colorectal liver metastases. Source: www.livermetsurvey.org.

124

SURGERY FOR METASTATIC COLORECTAL CANCER


FOLFIRI regimens were treated with cetuximab, resulting in
conversion of 7% unresectable patients to resectable.
Certainly, recent results form the randomized trials
(FOLFIRI vs. FOLFIRI/Cetuximab CRYSTAL trial; and
FOLFOX vs. FOLFOX/Cetuximab OPUS trial) (88,89)
add further evidence to the benefit conferred by cetuximab
on the response and resection rates in patients with
advanced CRLM treated with standard first-line therapies.
As a result of using combined chemotherapy regimens, the

Paul Brousse Hospital 473 patients (Apr. 88Jul. 99)


100

91%

Resectable: 335
Initially non-resectable: 138
No surgery

80
Survival (%)

66%
p = 0.01

60

48%

40

30%

52%
33%

20

23%
No surgery

0
0

5
6
Years

10

Figure 13.3 Curves demonstrating 5- and 10-year survival for initially resectable patients and for patients who underwent rescue surgery. Source : From
Ref. (82).

(A)

(C)

resection rates have significantly increased compared to


regimens of FOLFOX or FOLFIRI alone. Furthermore, in
two other studies, cetuximab conferred an increase in
response rate and resection rate over standard chemotherapy alone, with the benefits being the greatest for patients
with KRAS wild-type tumors; CRYSTAL 59% versus 43%
and OPUS 61% versus 37% (90,91).
Intra-arterial Chemotherapy
The interest in using intra-arterial chemotherapy in neoadjuvant setting has also progressively increased as it has been
demonstrated to have a high response rate in both the firstand second-line settings. Clavien et al., using HAI-FUDR
with or without leucovorin, induced resectability in 6 (26%)
of 23 previously treated patients. The actuarial survival rates
at 3 years were 84% for responders to neoadjuvant therapy
compared with 40% for nonresponders (92). In a Memorial
Sloan-Kettering study (93), 44 patients with extensive liver
metastases received HAI-FUDR and dexamethasone plus
oxaliplatin-based systemic chemotherapy as part of two Phase
I trials. The study population in this trial had a high number
of patients with more than 4 metastases, metastases greater
than 5 cm, more than 25% liver involvement with tumor, a
CEA level greater than 10 ng/dl and previously chemotherapy
exposure. Despite these negative parameters, the objective
response rate was 82%, resulting in complete gross resection
of tumor in 9 (20%) of the 44 patients and a median survival
for all patients of 26 months. Recently, preliminary data from

(B)

(D)
Figure 13.4 Unresectable colorectal liver metastases downsized by chemotherapy.

125

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


several clinical trials using the oxaliplatin or irinotecan via
HAI have been promising.
In summary, regardless the type of chemotherapy used in
unresectable patients, a significant proportion (1530%) is
switched to resectability. This proportion of patients will
probably expand with the increasing efficacy of chemotherapy
and biological agents, justifying a close collaboration of oncologists and surgeons in the multidisciplinary treatment of
these patients.
Techniques to Improve Resectability
In addition to preoperative chemotherapy, a number of interventional/surgical techniques are available to achieve a situation of resectability include tumor ablation techniques, portal
vein embolization, two-stage liver resection, and extended
liver surgery (total vascular exclusion and cooling).
Tumor Ablation Techniques
Locally ablative modalities such as radiofrequency ablation
(RFA) and cryotherapy are both techniques used either independently or as adjunctive to surgery. These techniques are
regarded as complementary to hepatectomy when complete
resection cannot be achieved. The strategy of using them can
result in an increased number of initially unresectable patients
in whom the curative treatment can be accomplished.

RFA is currently the most commonly applied ablation method. RFA involves localized application of
conductive thermal energy to destroy tumor cells.
Specifically alternating electric current in the range
of radiofrequency waves (460 kHz) is applied from a
generator through a needle electrode placed directly
into the tumor.

Limitations of RFA are related to the lesion size (suitable for


lesions 3 cm) or when a maximum of three tumors are present as well as the anatomical location of the tumor. In the
vicinity of large hepatic vessels, the heat sink effect significantly increases the risk of incomplete ablation. Also, the risk
of thermal injury is increased when nodules are close to main
biliary structures or to extrahepatic organs.
RFA procedure, when performed in combination with surgery, increases the resectability and curability for patients in
whom hepatic resection alone is not curative. Adding RFA to
hepatic resection has been reported to be well tolerated with a
perioperative morbidity and mortality comparable to those
seen after resection alone (94). For metastases considered as
unresectable, RFA combined with hepatic resection can
achieve a median survival as high 37 months (95).

126

Cryotherapy involves freezing and thawing of liver


tumors by means of a cryoprobe. Tumor necrosis
occurs by direct cellular freezing and indirectly
through vascular thrombosis and tissue anoxia.
Results of such treatment combined with hepatic
resection for patients not eligible for hepatic resection alone have shown a 5-year survival rate of 24%,
better than those obtained by palliative chemotherapy (96,97). Local recurrence at the site of cryotherapy occurs in 5% to 44% of patients and it has been

found that the rate increases when treating multiple


lesions (>8), large lesions (>3 cm), or tumors located
to major blood vessels (blood warmth may impair
the freezing process).

Portal Vein Embolization


Portal vein embolization (PVE), which was first described
by Makuuchi (98), is used to trigger a compensatory hypertrophy of the future remnant liver. In patients with an otherwise normal liver, current guidelines recommend
preoperative PVE when the ratio of the remnant liver volume is <30%. Patients submitted to prolonged chemotherapy with a high risk of induced hepatic lesions should
benefit from this method when this ratio is less than 40%.
PVE can be performed percutaneously or using the ilocolic
vein approach via a limited laparotomy. After PVE, hepatic
volume is routinely evaluated using CT scanner volumetry,
which gives information about the degree of the compensatory hypertrophy as well as the status of the metastatic disease. The optimal time interval necessary to induce
maximum hypertrophy after PVE has not been established
yet, although some Japanese teams use to perform resection
as early as 2 weeks after the PVE. The majority of groups,
however, would usually use a 4 to 6 weeks of interval
between PVE and surgery.
PVE is safe and does not add significant morbidity. In our
series, a significant increase of liver volume following preoperative PVE was observed in 43% of patients, allowing 63% of
originally unresectable liver metastases to be subsequently
operated (99). The feasibility and the influence on the outcome in patients requiring an extended hepatectomy has been
reported by other investigators also. Farges et al. (100) published the results of a prospective study of PVE performed in
patients undergoing right hepatectomy for either primary liver
cancer or metastatic liver disease. They demonstrated significantly fewer postoperative complications when PVE was used
to increase the FLR volume in patients with chronic liver disease whose anticipated FLR was <40%. In contrast, patients
with normal liver function who underwent a right hepatectomy did not benefit from PVE, as it was expected, since the
remaining liver usually represents more than 30% of the
functional liver volume.
In summary, the PVE needs to be performed only in patients
who are being considered for an extended right hepatic resection.
PVE is rarely necessary prior to extended left hepatectomy
because the right posterior sector typically constitutes about
30% of the total liver volume (101,102). On the other hand, in
patients who have been treated with heavy neoadjuvant chemotherapies with a high risk of induced parenchymal liver
lesions the PVE should be performed when the ratio of the
remnant liver volume to the total estimated liver volume is less
than 40%.
The selective use of PVE may enable safe and potentially
curative hepatic resection in a subset of patients with advanced
colorectal metastases who would otherwise have been marginal candidates for resection because of an inadequate FLR
or significant underlying liver disease.

SURGERY FOR METASTATIC COLORECTAL CANCER


Two-stage Hepatectomy
The concept of two-stage liver resection to deal with
multinodular CRC metastatic disease that cannot be
resected in a single procedure owing to a too small volume
of the future remnant liver was first described by our group
(103). During the first stage, the less invaded hemiliver
(usually left) is completely cleared of metastases by resection, which could be associated with a simultaneous portal
vein ligation/embolization of the most involved hemiliver
(usually right) or percutaneous portal vein embolization
1 week later. The aim of this step is to minimize the risk
of liver failure by performing a second and complete
resection once regeneration induced by the portal vein

embolization has taken place. Finally a second stage hepatectomy will be carried out to completely remove the liver
harboring the remaining metastases (Fig. 13.5). The success of this method relies on the liver regeneration between
the two interventions, allowing the second hepatectomy to
be performed with a lower risk of complications, including
liver failure.
Our experience, as well as that of others, has demonstrated
that this strategy can be carried safely and effectively in
selected patients with initially nonresectable multiple bilobar
CRLM (104107) (Table 13.3). In our latest study, the 3- and
5-year survival rates were 60% and 42%. It should be mentioned that during the first stage performing nonanatomic

(A)

(B)

(C)

(D)

Figure 13.5 Radiological follow-up of a patient treated with combination of neoadjuvant chemotherapy and two-stage hepatectomy. 1A, hepatic metastases before
chemotherapy treatment. 1B, planning of surgery after tumor downstaging (before the first hepatectomy). 1C, first hepatectomy. 1D, liver remnant following the
second hepatectomy (segments IV and I).

Table 13.3 Reported Survival Outcomes after Two-Stage Hepatectomy for Colorectal Liver Metastases
Patient survival (%)
Author/Institution

No of
patients

Success rate
(%)

Mortality rate
(%)

Morbidity rate
(%)

Median
(months)

3 years

5 years

Adam et al. (2000)


Jaeck et al. (2004)
Shimada et al. (2004)
Togo et al. (2005)
Adam et al. (2007)

16
33
12
11
45

81
76
100
100
69

15
0
0
0
6.5

45
56
NA
18
48

31

18
35

35
54

45
47

28

NA, not available.


The mortality rates concern the second operation.

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SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


wedge resection is advantageous as it preserves a maximal
amount of liver parenchyma that will hypertrophy after PVE
to become the functional liver remnant. Also, our policy is to
perform portal ligation and embolization with absolute
alcohol during the first liver resection to avoid a second
procedure before the definitive hepatectomy.
Currently, the guidelines for two-stage hepatectomies
include the following:

No residual tumor should be left in the future remnant liver at the first intervention.
If the resection alone cannot remove all lesions, one
of the ablative methods (RFA, cryotherapy) has to be
used for local tumor destruction in order to prevent
tumor progression during the regeneration of the
remnant liver.
At the first intervention, portal dissection and mobilization of the lobe that is to be resected during the
second intervention should be avoided.

In summary, based on the nature of the metastatic disease


(number, size, and distribution), the treatment strategies,
which can be applied with the aim of achieving a complete
treatment of CRC liver metastases include the following:

Patients with unilobar multinodular metastases requiring resection of more than 60% to 70% of the functional liver parenchyma should undergo preoperative
portal vein embolization. Following PVE, the induced
hypertrophy of the future remnant liver allows for a
curative resection while minimizing the risk of postoperative hepatic insufficiency (Fig. 13.6A).
Patients with bilobar multinodular metastases for
which a planned resection would leave no more than
three nodules and none larger than 3 cm in the
remnant liver are preferentially treated with a
multimodal approach consisting of hepatic resection combined with RFA or cryotherapy of the
unresectable nodules (Fig. 13.6B).

Right lobectomy
Remnant liver <30%

Portal vein embolization


(A)

Patients with bilobar multinodular metastases for


which a planned resection would leave more than
three nodules or any nodule larger than 3 cm in the
remnant liver could be candidates for two-stage
hepatectomy (Fig. 13.6C).

Extended Liver Surgery (Total Vascular Exclusion and Cooling)


Involvement of the IVC and/or the confluence of hepatic
veins by liver metastases is another situation that can be considered as a contraindication to liver resection. Currently,
employing total vascular exclusion (TVE) of the liver and
vascular reconstruction techniques can make surgery possible without taking further risks for this specific group of
patients. As the experience has grown with TVE, an increasing number of patients are being operated with acceptable
morbidity and mortality. Conventional TVE consists of
clamping of the liver inflow (Pringle maneuver) as well as
clamping of the supra and infrahepatic vena cava. Alternatively, in cases with no caval involvement by the tumor, selective control of the hepatic veins can be achieved allowing
preservation of the caval flow. In cases whereby the caval
clamping is associated with hemodynamic disturbances
(hypotension), a venovenous bypass is necessary through
which venous blood from femoral and portal vein is diverted
to axillary or internal jugular vein. A drawback of these techniques, however, is that almost inevitably would induce
warm ischemia for which the maximal duration of tolerance
is assumed to be around 60 to 90 minutes. For cases which
require interruption of hepatic blood flow for more than
60 minutes, hypothermic perfusion of the liver should be
instituted to prevent the consequences of a long warm ischemic time. Such combination was evaluated in a study conducted in our center, which demonstrated that TVE combined
with hypothermic perfusion was associated with a better
ischemic tolerance and liver function as well as significantly
lower complication rates compared to TVE 60 min. Combined liver and vena cava resection is another procedure
facilitated by combined TVE and hypothermic perfusion. In

Right hepatectomy
3 Metastases 30 mm (remnant liver)

Right hepatectomy
>3 Metastases > 3 mm (remnant liver)

Hepatectomy + RFA or cryo


(B)

Two stage hepatectomy


(C)

Figure 13.6 Diagrammatic illustration of the surgical strategies used when treating patients with nonresectable multimodal metastatic disease. (A) Multifocal
unilobar metastases. (B) Multifocal bilobar metastatases. (C) Multifocal bilobar metastases. RFA, radio frequency ablation; Cryo, cryotherapy.

128

SURGERY FOR METASTATIC COLORECTAL CANCER


a series from our center (108), out of 22 patients who underwent such a procedure, one patient died (4.5%) during the
perioperative course, whereas 14 patients (64%) developed
complications. Overall 5-year survival for the operated
patients was 38.3%, comparing favorably with other reported
results.
Hence, combining TVE with vascular reconstruction
techniques has resulted in an increased number of patients
undergoing surgery for CRC liver metastases involving
vena cava and/or the confluence of hepatic veins (which not
so long ago were considered as a contraindication to surgery). This approach, however, seems justified only for surgical teams experienced in both hepatobiliary and vascular
surgery.
Repeat Liver Resection for Recurrent Metastatic Disease
Despite hepatic resections with a curative intent in wellselected patients, up to 60% subsequently will develop recurrent liver metastases. Of these, approximately 20% to 30%
present with isolated recurrent liver metastases, which are
potentially amenable to further resection.

Regardless of the technical challenges due to adhesions


and altered anatomy of the liver, the repeat hepatectomy is
safe with a postoperative mortality and morbidity not different from those reported after a first resection (median
survival approaches 2 years) ( Table 13.4). Five-year survival
rates ranging from 16% to as high as 41% have been
reported (109111). Not surprisingly, the same prognostic
factors that predict favorable outcome after primary resection apply to the repeated liver resection, including complete removal of metastatic lesions with satisfactory margins
and no extrahepatic disease.
Furthermore, a study conducted by our team demonstrated that a third hepatectomy is safe, with complication
rates and survival benefit similar to first and second hepatectomies (112) (Fig. 13.7). The overall 5-year survival following the third hepatectomy was 32% and disease-free survival
was 17%. Similarly, Pessaux et al. showed overall 5-year survival rates of 33%, 21%, and 36%, respectively, after a first,
second, and third hepatectomy (113). Also, in repeat resections, the general rule applies that it does not matter how
many lesions the patient has, provided that an R0 resection

Table 13.4 Reported Survival Outcomes after Repeat Liver Resection for Recurrent Colorectal Metastases
Patient survival (%)
Author/Institution

Year

Fernandez et al.
Adam et al.
Yamamoto
Muratore et al.
Suzuke et al.
Petrowsky et al.
Adam et al.
Shaw et al.

1995
1997
1999
2001
2001
2002
2003
2006

No of patients
170
64
75
29
26
126
199
66

1 years

3 years

5 years

87
48

86
89

45
60
31
35
62
51
46

32
41

32
34
32
44

(%)
100

89%

First hepatectomy
Second hepatectomy

88%

80

Third hepatectomy

82%
54%
60

40

46%

36%

42%

32%
28%

20

0
0

Patients at risk
First hepatectomy
Second hepatectomy
Third hepatectomy

2
No
416
139
6

3
1 yr
267
80
49

2 yrs
169
37
31

4
3 yrs
120
27
15

4 yrs
83
19
10

5 Year
5 yrs
60
13
6

Figure 13.7 Survival after 1st, 2nd, and 3rd hepatectomy from the time of the index operation. Source: From Ref. (112).

129

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


can be achieved within limits of safety in terms of liver volume
and function.
Therefore, hepatic recurrences should be regarded as oncologically similar to metastatic disease at initial presentation
and repeat hepatectomies should therefore be offered to
patients based on the same criteria as those used for initial
hepatectomy.
Special Considerations
Despite the advances made in the management of CRLM,
there are still some areas of uncertainty or debatable. For
instance, it is not clear what type of treatment is needed after a
complete clinical response (total disappearance of metastases
while on chemotherapy). Similarly, the management of synchronous presentation of primary colorectal cancer and
hepatic metastases is still disputed (chemotherapy or upfront
surgery) and so is the issue of which site should be operated
firstbowel or liver?
Treatment of the Lesions That Have Disappeared After
Neoadjuvant Treatment
With the advances in chemotherapy efficacy, the frequency of
missing metastases has increased. Nevertheless, the treatment strategies concerning such lesions are not well defined,
particularly so when trying to decide about the necessity to
resect, the time, and type of resection.
In a study conducted by our team (82), we initially reported
that up to 7.2% of the patients with unresectable CRLM
treated with systemic chemotherapy developed complete
metastatic necrosis. Hence, we recommended that preferably
all tumor-bearing sites must be resected during the surgery
for CRLM. And, while later on, it was suggested that missing
metastases are cured in 70% of the cases (114), increasingly,
the evidence indicates the contrarya persistence of
histologically active tumor in as many as 83% of the lesions,
which have a complete radiological response on imaging
(115). Furthermore, a subsequent report from our unit (116)
demonstrated that the actual number of patients with no
more residual tumor cells (complete pathological response,
CPR) in CRLM after neoadjuvant chemotherapy was even
smaller (4.5%) than the one previously reported rate, which
is in keeping with reports from other centers (117). Considering these results, we can say that a complete radiological
response does not mean complete histological response, and
despite the favorable long-term results associated with the
CPR (5-year survival of 76%) the utility of surgery remains
unchallenged. This view is supported by several reasons: (1)
Confirmation of CPR depends primarily on the accuracy of
the pathologic examination and on the exhaustivity of histologic sampling as undetected malignant cells could still be
present in the resected lesion/s. By resecting all metastases,
the possibility of leaving residual tumor cells behind is greatly
reduced; (2) During the laparotomy it is often possible to
diagnose additional metastatic disease, which otherwise
would have remained undetected by the standard investigative tools; (3) The diagnosis of the CPR is a retrospective
one as there is no imaging technique, which can reliably diagnose CPR preoperatively, hence, only surgical resection with

130

concomitant pathological examination is able to make a


definite diagnosis.
In practice, due to very low overall incidence of CPR (4%),
patients who have a complete radiological response should be
operated on.
Patients treated with neoadjuvant chemotherapy should be
referred to surgeons before the initiation of the treatment, so as
to avoid eventual difficult decisional situations brought about
by the inability to localize previously seen radiological lesions.
Synchronous Metastases
Neoadjuvant chemotherapy or upfront surgery? The
interest in using preoperative chemotherapy for
resectable patients has been increasing. The rationale
for this policy has been supported by the better prognosis obtained with neoadjuvant chemotherapy and
surgery, compared to upfront surgery in patients
with synchronous CRLM. Administering neoadjuvant chemotherapy not only can be associated with a
lower rate of positive surgical margins compared to
the rates observed in patients treated with upfront
surgery (118), but also such approach provides time
to identify a subgroup of patients who will develop
progressive disease while on chemotherapy (119).
Concerning the later group (patients with progressive disease while receiving neoadjuvant chemotherapy), a study conducted by our team showed that
such patients had a 5-year survival of 8% versus that
of 37% observed on patients with an objective tumor
response to neoadjuvant chemotherapy (119). In
addition, a study conducted by Rubbia-Brandt et al.
(117), using a tumor regression grade scoring system,
identified that resected patients with a poor histological response to chemotherapy had a lower disease-free
survival at 3 years and a lower overall survival at
5 years. Certainly taking into consideration these
results, the utility (benefit) of surgical intervention in
this subgroup of patients has to be questioned.
Therefore, the decision to give neoadjuvant chemotherapy should
be individualized and based on specific clinical situations.

In patients who are chemonave with four or more


synchronous CRLM and a nonocclusive primary,
neodjuvant chemotherapy can be appropriate followed by repeated MRI and PET CT.
Neoadjuvant chemotherapy can also be administered in patients with two to three bilobar CRLM. By
contrast, if a patient belonging to this group has
comorbidities or there is a concern about chemotherapy-related hepatotoxicity at a time when an
extended resection is required, initial surgery would
be indicated.
Instead for patients with one to two unilobar metastatic diseases, upfront surgery should be considered
first.
Single or staged intervention? The optimal timing for
resection of synchronous CRLM and the primary
tumor remains a matter of controversy. Most surgeons

SURGERY FOR METASTATIC COLORECTAL CANCER


prefer a staged approach with initial resection of the
colorectal primary followed by hepatic resection 8 to
12 weeks after. Supporters of this strategy argue that
the combined approach is associated with increased
morbidity and mortality (Level of evidence: 3). Nordlinger et al. (120) reported an operative mortality of
7% for combined resection compared to 2% for
staged resection. Bolton and Fuhram (121) in their
series reported a mortality rate of 12% for combined
resections, which increased to 24% for those who
underwent major liver resection. Reddy et al. (122), in
a multi-institutional retrospective study comparing
postoperative outcomes after simultaneous and
staged colorectal and hepatic resections, concluded
that caution should be exercised before performing
simultaneous colorectal and major hepatic resections.
For major hepatectomy, simultaneous colorectal
resection increased mortality (8.3% vs. 1.4%, p < 0.05)
and severe morbidity (36.1% vs. 15.1%, p < 0.05) as
compared to combined minor liver and colorectal
resection. Similarly, a recent study demonstrated that
patients who underwent a combined resection had a
higher mortality rate (10%) compared with patients
treated by staged resection (1.1%), concluding that
combined interventions should be performed in wellselected patients, <70 years old and not with rectal
surgery (123).
On the other hand, several studies have also reported that
simultaneous resection of the colon and liver tumors results
in morbidity and mortality comparable to staged resection
(124,125). However, in the majority of these studies, the
patients submitted to simultaneous resection, underwent limited liver resection, and were much more selected compared to
those who underwent staged surgery by the same teams. In
practice, simultaneous resections should be decided on an
individual basis. Combined resections may be more appropriate in patients who require a straightforward colon resection
and a limited liver resection (2 segments). Patients who
require major liver resections particularly the elderly should
be dealt with by staged resection. Ultimately, the final decision
should be made by the operating surgeon based on the experience and the risk evaluation.
In summary, it is recommended that colorectal and major
liver resections (>3 segments) should not be performed during the same time. One-stage procedure (combined liver and
colorectal resection) should be reserved for experienced teams
sharing both colorectal and liver surgery expertise.
Surgery for Synchronous Liver Metastases:
Liver or Colon Resection First?
The standard approach for synchronous CRLM consists of
resection of the primary tumor followed by chemotherapy for
3 to 6 months with the goal of resecting the liver metastases if
they stabilize or respond. However, this strategy has pitfalls as
many patients have progression of their metastatic disease
while being treated for their primary, precluding eventual

surgery with curative intent. Based on this observation, Mentha


et al. (126) designed a management strategy that involves highinduction chemotherapy first, followed by liver surgery, and
completed by removal of the primary colorectal tumor. Such
strategy aims at controlling the CRLM at the same time as the
colorectal primary, optimize the chances of curative liver resection, and allowing the administration of well-programmed
chemoradiotherapy before rectal surgery (when indicated). The
authors have shown that the new reverse approach produced
resectability and survival rates better than those expected from
the published data on patients treated conventionally for disease of similar severity (3-year survival of 86%). The obvious
candidate for this treatment would be a patient with nonobstructive primary colonic tumor. The rationale of this approach
is that in the majority of patients the most life-threatening site
is represented by the liver.
In summary, the first treatment should focus on the global
metastatic disease rather than locally treat the primary
tumor: primary chemotherapy seems to be better than primary resection.
For unresectable liver metastases with a primary colorectal
cancer in place, chemotherapy as the first treatment line
does not alter the survival expectancy. The first surgical procedure should logically deal with the tumor site, which is
more difficult to resect and more likely to be life threatening
for the patient.

conclusions
The surgical treatment of colorectal hepatic metastases represents the only potentially curative therapeutic option able
to achieve long-term survival and a hope for cure. Newer
treatment strategies have shifted from the traditional concept
of successive lines of medical therapy to that of a continuum
of care in which medical and surgical treatment combinations are tailored to the clinical settings. To optimize the
treatment of CRLM, management by a multidisciplinary
team consisting of oncologists, surgeons, and radiologists is
of the utmost importance.
Advances in body and hepatic imaging has allowed for more
accurate selection of patients with colorectal liver metastases.
Imaging modalities are now able to detect minimal metastatic,
which not very long ago would have been very difficult to do so.
The significance of the prognostic factors has changed,
although helpful in stratifying patients with regards to prognosis, should not be used to exclude otherwise resectable
patients from surgery.
Data on the use of neoadjuvant and adjuvant therapy to
decrease recurrence risk and improve survival in patients with
initially resectable metastases are encouraging, while further
evidence and assessment is needed.
With newer chemotherapy regimens, a significant proportion of unresectable patients are currently switched to resectable, opening the way to a survival benefit, which is not very
different to that of initially resectable patients.
The use of modern surgical techniques has resulted in
a reduction of perioperative mortality and morbidity,
whereas tumor ablation techniques, PVE, and radical liver

131

SURGICAL MANAGEMENT OF HEPATOBILIARY AND PANCREATIC DISORDERS


surgery in combination with neoadjuvant chemotherapy
have positively influenced the expansion of candidates for
surgical resection. In addition, with the use of more active
systemic chemotherapy as adjuvant therapy, we hope that an
improved survival rate in resected patients will be observed.
In patients with tumor recurrence following hepatectomy
for CRLM, repeat hepatectomies provide long-term survival
benefit similar to that of first hepatectomy. In future, better
patient selection through improved imaging techniques and
identification of genomic markers as well as further advances
in pharmacotherapy will likely further improve the outcome
for patients with CRLM.

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