Gastrointestinal Oncology - part 1 ppt

23 and Esophageal Cancer Diane Hershock, MD, PhD Chapter 4: Surgical Approach to Gastric and Gastroesophageal Neoplasms.. A longer duration of reflux symptoms sep-arates BE from non-Barr

Michael L Kochman, MD, FACP

Professor of Medicine Co-Director, Gastrointestinal Oncology Gastroenterology Division University of Pennsylvania Philadelphia, Pennsylvania

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D EDICATIONThis book is dedicated to my family: my wife, Mary, and my children Elyse andSidney, without their indulgence this book would not have been possible.

Over the years a number of key individuals sparked and nurtured my interest in trointestinal oncology Thomas Lad, MD and Jay Goldstein, MD were critical early on

gas-in demonstratgas-ing to me the need for better diagnostics and additional effective therapies.Tachi Yamada, MD and Chung Owyang, MD had the foresight to allow me the spe-cialized training, which I hope I have put to good use Drs Rick Boland, John DelValle,Grace Elta, Robert Hawes, Peter Traber, and Maurits Wiersema were instrumental inhelping me acquire and define my skillset and in facilitating my clinical research Mycurrent colleagues at the University of Pennsylvania have been instrumental, with DanHaller, MD at the forefront

Clifford Pilz, MD deserves special mention as Chief of Medicine during my medicalschool, residency, and Chief Residency; he clearly defined the epitome of the all-know-ing physician; no question was too small to deserve an answer, no sign or symptom toosubtle to be ignored

C ONTENTS

Dedication v

Acknowledgments ix

About the Editor x

Contributing Authors xi

Preface xiii

Chapter 1: Management of Premalignant Diseases of the Esophagus: 1

Barrett's Esophagus Richard E Sampliner, MD Chapter 2: Surgical Approaches to Esophageal Neoplasms 11

John C Kucharczuk, MD Chapter 3: Approach to Chemotherapy and Radiation for Gastric 23

and Esophageal Cancer Diane Hershock, MD, PhD Chapter 4: Surgical Approach to Gastric and Gastroesophageal Neoplasms 53

Francis (Frank) Spitz, MD Chapter 5: Identification and Management of Familial Pancreatic Cancer 67

Stephen J Rulyak, MD, MPH Chapter 6: Surgical Approach to Ampullary and Pancreatic Neoplasia 87

Kristoffel R Dumon, MD; Robert J Canter, MD; and Noel N Williams, MD Chapter 7: Chemotherapy and Radiation in the Treatment of Pancreatic 107

Cancer Bapsi Chak, MD and Jordan Berlin, MD Chapter 8: Endoscopic Retrograde Cholangiopancreatography 125

in the Management of Pancreaticobiliary Neoplasia Ilias Scotiniotis, MD Chapter 9: Screening and Surveillance Strategies for Colorectal Cancer: 141

Average- and Increased-Risk Individuals Carla L Nash, MD and Arnold J Markowitz, MD Chapter 10: Surgical Approach to Colorectal Neoplasia and High-Risk 157

Conditions

Najjia N Mahmoud, MD and J.J Karmacharya, FRCS

Chapter 11: Approach to Chemotherapy and Radiation Therapy 183

for Colorectal Neoplasia Weijing Sun, MD Chapter 12: The Assessment and Management of Acute and Chronic 195

Cancer Pain Rosemary C Polomano, PhD, RN, FAAN; Allen W Burton, MD; Niraja Rajan, MD; and Patrick M McQuillan, MD Chapter 13: Endoscopic Ultrasound in the Diagnosis and Staging 223

of Gastrointestinal Malignancy Janak N Shah, MD Color Atlas CA-I Chapter 14: Interventional Radiology 243

Karen T Brown, MD; Anne Covey, MD; and Lynn A Brody, MD Chapter 15: Maintenance of Luminal Patency: Dilation, Endoprosthetics, 285

and Thermal Techniques Patrick R Pfau, MD Chapter 16: Gastrointestinal Cancer: Diagnosis and Management 307

of Nutritional Issues James S Scolapio, MD and Alan L Buchman, MD, MSPH Chapter 17: Chemoprevention for Gastrointestinal Neoplasia 327

Paul J Limburg, MD, MPH and Navtej Buttar, MD Chapter 18: New Technologies for the Detection of Gastrointestinal 365

Neoplasia Linda S Lee, MD and John M Poneros, MD Appendix A: Esophageal Cancer Staging 385

Appendix B: Gastric Cancer Staging 387

Appendix C: Pancreas Cancer Staging 389

Appendix D: Colon and Rectum Cancer Staging 391

Index 393

viii Contents

A CKNOWLEDGMENTS

I would like to thank the chapter authors who clearly did a phenomenal job veying their expertise in their respective areas It is difficult in these times to have gen-uine experts write chapters due to the complex time demands placed upon them; theyare to be congratulated

con-The staff at SLACK Incorporated was superb and demonstrated great ism; their guidance and expertise shows in the polish of the final product An individ-ual thanks is due to Carrie Kotlar, without her persistence (and perseverance) this hand-book would not have come to fruition

professional-A BOUT THE E DITORMichael L Kochman, MD, FACP is Professor of Medicine in the GastroenterologyDivision at the University of Pennsylvania Medical School and Hospital of theUniversity of Pennsylvania He is the Endoscopy Training Director and Co-Director ofthe Gastrointestinal Oncology Program Dr Kochman is a graduate of NorthwesternUniversity (1982) and the University of Illinois Medical School at Chicago (1986).

At the University of Pennsylvania, he has served on various committees including thePhysicians Billing Oversight Committee and Departmental Review Committees.Within the GI division he has served as Fellowship Chairman and has received a num-ber of teaching awards including the Sid Cohen, MD award for the education of fellows

Dr Kochman has served many local and national societies in a variety of positions.Currently he is President of the Delaware Society for Gastrointestinal Endoscopy and isthe Program Chairman for the Pennsylvania State Gastroenterology Society His majornational commitments are to the American Gastroenterological Association (AGA) andthe American Society for Gastrointestinal Endoscopy (ASGE) He has served the AGA

on the Education Committee and the Program Committee and is currently a member

of the Clinical Practice Committee For the ASGE, Dr Kochman has served on the Graduate Education Committee, the EUS SIG and is currently a member of theResearch Committee and the Program Committee

Post-Dr Kochman is the Chairman of the Editorial Board of Gastrointestinal Endoscopy, and is coeditor for Techniques in Gastrointestinal Endoscopy and the Yearbook of

Gastroenterology He also serves on the editorial boards and as a reviewer for a number of

journals including Annals of Internal Medicine and Gastroenterology Dr Kochman has

published over 120 articles and chapters and a number of videos He has edited 4 lished books and is currently editing 3 books to be published in the near future

Memorial Sloan-Kettering Cancer Center

New York, New York

Karen T Brown, MD

Memorial Sloan-Kettering Cancer Center

New York, New York

Memorial Sloan-Kettering Cancer Center

New York, New York

Rosemary C Polomano, PhD, RN, FAAN

University of Pennsylvania School ofNursing

Philadelphia, Pennsylvania

John M Poneros, MD

Brigham and Women’s HospitalBoston, Massachusetts

Francis (Frank) Spitz, MD

University of Pennsylvania Health SystemPhiladelphia, Pennsylvania

P REFACEThe area of gastrointestinal oncology is an active one Both clinical research and basicresearch have come together and changed the diagnostic and treatment protocols for anumber of deadly malignancies A multidisciplinary approach to the diagnosis and treat-ment appears to be the best paradigm; it allows for each individual medical specialty toapply their knowledge and expertise in an expeditious and effective manner.

Some of the cancers with which we deal are unfortunately all too often ultimatelyfatal Our roles are changing; the boundaries between the medical subspecialties areblurring, with progressive leadership we are better able to make the patients feel thattheir “team” is truly in sync and providing cutting edge therapy To this end, I have gath-ered a nationally and internationally recognized group of clinical researchers and clini-cians to provide a balanced and multidisciplinary approach to the treatment of the mostcommon of the gastrointestinal malignancies

It is intended that this book will serve as a resource for trainees and clinicians in themedical and surgical fields Those that infrequently diagnose or take care of patientswith these neoplasms should be able to find enough easily accessible information to beable to converse with their patients and their families, and those who are routinelyinvolved in the care of these patients will gain a better understanding of the capabilities

of the other specialties and gain insight into the thought processes behind the often ficult treatment decisions that must be made

dif-E PIDEMIOLOGYThe epidemiology of BE is incompletely identified and derived mostly from cohortstudies of patients with BE These studies are retrospective, prospective, and subject tothe variability of disease definition, referral bias, and the specifics of the populationserved at the study site The mean age of diagnosis is 63 years and the estimated meanage of onset is 40 years.2Patients with BE are predominantly male—2:1 male to femaleratio.3The frequency of BE differs dramatically among ethnic groups The prevalence of

BE in adults undergoing endoscopy ranges from 7.8% of Whites to 4.8% of HispanicAmericans and 1.1% of African Americans A longer duration of reflux symptoms sep-arates BE from non-Barrett’s GERD patients as a group, but there is a great overlap ofindividual patients An earlier age of onset of GERD may also be a characteristic of BE.Reports of families with generations of patients with BE suggest familial aggregation.First-degree relatives of patients with BE and EAC are more likely to have a history ofGERD than first-degree relatives of patients with reflux esophagitis.4Familial aggrega-tion of BE, EAC and adenocarcinoma of the esophagogastric junction has been demon-strated in White adults

Hiatal hernia is commonly associated with BE and contributes to the ogy Ninety-six percent of patients with long segment BE have a hiatal hernia.5In fact,

pathophysiol-a predictive model for the length of BE uses the length of the hipathophysiol-atpathophysiol-al hernipathophysiol-a pathophysiol-and the durpathophysiol-a-tion of esophageal acid exposure.6On average, patients with BE have greater esophagealacid and bile acid exposure than GERD patients without mucosal disease

dura-S CREENING FOR B ARRETT ’ S E SOPHAGUSThe rationale for screening for BE is that it is the premalignant lesion for EAC.Recognition of BE allows an opportunity for early recognition of EAC to enable inter-vention and improvement of outcome The rising incidence of EAC has been docu-

Table 1-1

D EFINITION OF B ARRETT ’ S E SOPHAGUS

1 Abnormal appearing distal esophagus mucosa

2 Intestinal metaplasia by biopsy

mented since 1975 and continues to climb EAC has increased from 5% of esophagealcancers to more than 50% in the last 30 years Unfortunately, less than 5% of patientswith EAC have been previously identified with BE Only prior detection of BE allowsfor early intervention.

The annual incidence of EAC in patients with BE has been controversial A funnelanalysis demonstrated publication bias with series with smaller numbers of patients withshorter follow-up having a higher incidence of cancer.7This analysis as well as a prospec-tive cohort study suggests the annual incidence to be 0.5%.8Even these data are subject

to bias from an inadequate length of follow-up A young patient with BE does not have

a greater risk of EAC than an older one just because he has a much longer life

expectan-cy A more realistic estimate of mortality from EAC can be derived from a populationbased and a cohort study demonstrating a mortality from EAC in patients with BE of4.7% and 2.5% respectively.9,10The lifetime risk of dying from EAC may be a conceptthat can be grasped by patients more readily than annual incidence Patients with BE areusually surprised and reassured that this risk is less than 5%

The epidemiology of BE and EAC provides information on who is at higher risk forhaving these diseases (Table 1-3) Who should we screen for BE? Older White maleswith chronic reflux symptoms will have the highest yield of BE Evidence-based thresh-olds for a specific age and years of reflux symptoms are not established A VeteransAffairs Medical Center study found an age of more than 40 years with heartburn at leastweekly to be predictive of BE.11There is a 2 phase risk stratification that is necessary:those patients at risk for BE and those with BE at risk for EAC The risk factors for EACare similar to those for BE—85% of patients with EAC are White men Increased fre-quency, severity, and duration of reflux symptoms are risk factors for EAC This was doc-umented in a Swedish population-based study Combining long duration with severity

of reflux symptoms has an odds ratio of EAC of 43.5 compared to controls lackingGERD.12

Trials of screening a random sample of the population for BE do not exist BE caneven occur in patients lacking evident GERD symptoms This provides a formidablechallenge for screening In a predominantly male (90%), veteran, and White (73%)group with a mean age of 61 undergoing sigmoidoscopy screening, 7% had long seg-ment BE and 17% short segment.13These surprising findings were not substantiated in

a larger study of patients with a mean age of 59, 60% male, and 78% White ing colonoscopy Only 0.36% had long segment and 5.2% short segment BE.14Longsegment BE is uncommon in patients lacking reflux symptoms

undergo-Management of Premalignant Diseases of the Esophagus 3

S URVEILLANCE E NDOSCOPYOnce BE is diagnosed, the next step is surveillance in an effort to detect high gradedysplasia (HGD) and EAC for effective intervention Dysplasia is the currently availableclinical biologic marker predicting cancer Dysplasia is the first step of the neoplasticprocess It is characterized by cytologic and architectural changes in intestinal metapla-sia that typically involve the surface epithelium Although a higher grade of dysplasia isassociated with a greater risk of EAC, even HGD may apparently regress and may notprogress to cancer over even a decade Progression from HGD to cancer ranges from59% in 5 years15to 16% in 7 years.16However, eliminating patients referred for HGDand cancer that develop within the first year of follow-up (prevalence EAC) reduces thehigher rate to 24% at 5 years, a still significant risk All patients with BE and HGD donot inevitably progress to cancer over their lifetime.

The problem with dysplasia as the basis for surveillance is the interobserver ity Even expert gastrointestinal (GI) pathologists have only a fair agreement in differ-entiating HGD from intramucosal cancer—kappa value of 0.56.17This interobservervariability is not overcome by training Unfortunately, this basis of clinical decision mak-ing is not a clear cut endpoint

variabil-Surveillance endoscopy is intrinsically reasonable and uniformly practiced in theUnited States,18although proof of efficacy is lacking Retrospective surgical series docu-ment a significantly greater survival in patients with cancer found at surveillanceendoscopy than patients clinically presenting with EAC (62% to 90% vs 20%) Recentcase-control studies also suggest that endoscopy is associated with earlier stage cancerand improved survival.19,20The frequency of surveillance endoscopy is based on thegrade of dysplasia (Table 1-4).21The intervals are derived from prospectively followedpatient cohorts and the biopsy protocol is based on modeling studies With no dyspla-sia on two consecutive endoscopies, an interval of at least 3 years is recommended Withlow grade dysplasia (LGD) after a second endoscopy confirming no higher grade of dys-plasia in the esophagus, endoscopy is recommended annually until no dysplasia isdetected in 2 consecutive endoscopies The standard biopsy protocol includes biopsies

of any mucosal irregularities and four-quadrant every 2 cm HGD will be discussed next

Table 1-4

S UGGESTED S URVEILLANCE FOR B ARRETT ’ S E SOPHAGUS

Dysplasia Grade Evaluation Endoscopy Frequency

LGD Highest grade on second Annual until no dysplasia x 2

endoscopyHGD Repeat endoscopy with Mucosal irregularity (EMR)

intensive large forceps biopsy protocolExpert pathologist inter- Individualize interventionpretation

M EDICAL T REATMENTThe mainstay of medical therapy is proton pump inhibitor therapy The goal of ther-apy for patients with BE is control of reflux symptoms and healing of accompanyingerosive esophagitis Symptom control often requires BID dosing (Figure 1-1) Even withappropriate timing prior to meals, esophageal pH is still abnormal in 25% of patientswith BE.22Patients with postprandial and supine regurgitation may benefit from meto-clopramide prior to a late meal Additionally, intermittent H2receptor antagonist usemay be of benefit.

Patients with refractory regurgitation and volume reflux, are candidates for surgicalfundoplication Currently, this is performed less invasively and with shorter hospital stay

by laparoscopy Although short term effectiveness is to be expected, a longer term

medi-an follow-up of 5 years in 85 BE patients demonstrated recurrent symptoms in 20%.23

The long term symptomatic durability of surgery is a concern, especially in patients withBE

Resectional surgery has a definitive role in patients with EAC It is the only therapyresulting in long-term cancer-free survival The long-term survival is excellent for early

stage disease TNM staging is utilized (ie, tumor, nodal involvement, and distant

metas-tases) (see Appendix A) Endosonography provides the most accurate assessment ofdepth of wall invasion and mediastinal involvement can be directly determined with fineneedle aspiration Intramucosal EAC cancer in the lamina propria and above the mus-cularis mucosa has less than 5% risk of regional lymph node spread in contrast to sub-mucosal cancer with a 25% risk With the recognition of the dependence of operativemortality on the institutional volume of esophagectomy, there has been increased moti-vation to send patients for surgery to high volume centers.24,25The role of surgery in themanagement of HGD will be discussed below

M ANAGEMENT OF H IGH G RADE D YSPLASIAThe management of HGD is complicated by problems including endoscopic sam-pling, histologic interpretation, variable natural history, coexistence of unrecognizedEAC, patient comorbidity, and inconsistent institutional expertise (Figure 1-2) HGD iscommonly not visible at endoscopy so that even though a biopsy protocol is systematic,the specific site involved may not be targeted Therefore, the first step in managing apatient with HGD is to repeat the endoscopy using a therapeutic endoscope and a large

Management of Premalignant Diseases of the Esophagus 5

Figure 1-1 Medical

man-agement of Barrett’s phagus

Eso-Proton Pump Inhibitors

Symptom Control Unrelieved Symptoms

Long-term maintenance

Surveillance endoscopy

BID dosing

Regurgitation: Considerfundoplication

capacity biopsy forceps to obtain larger samples Four-quadrant biopsies are performedevery 1 cm Biopsies from each level are placed in a separate container to help localizethe HGD Any mucosal irregularity should also be separately biopsied HGD found inthe biopsy of a nodule should be considered a cancer until proven otherwise This is theideal setting to apply the new technique of endoscopic mucosal resection This provides

a large sample—usually 1 cm—to more effectively stage the disease for therapeutic sion making The finding of intramucosal cancer could lead to topical (endoscopic) ther-apy Invasion of the muscularis mucosa would lead to an esophageal resection in apatient who is a good surgical candidate because of the risk of regional lymph nodespread

deci-An expert GI pathologist should then confirm the reading of HGD At this point, it

is worthwhile to sit down with the patient and his or her partner to discuss theoptions—intensive endoscopic surveillance, endoscopic ablation therapy, or esophagec-tomy This decision should be individualized based on the patient’s age, medical condi-tion, and preferences A year of surveillance endoscopy every 3 months should not pose

a risk of delayed diagnosis in a patient without mucosal irregularities The finding ofcancer at any endoscopy usually simplifies decision making Factors favoring surgeryinclude younger age, good cardiopulmonary condition, multifocal HGD, recurrentlyidentified HGD, and the availability of a high volume surgical center Favoring endo-scopic surveillance or therapies include an aged patient, major comorbidity, and localendoscopic expertise

Photodynamic therapy using porfimer sodium as the photosensitizer has beenrecently approved by the FDA for patients with BE and HGD A multicenter random-ized trial with a 2-year follow-up documented significant improvement in eradication ofHGD (77% vs 39% in the nonendoscopically-treated control group) and development

of EAC (13% vs 28%).26 This option offers no procedural mortality and retainedesophageal function One third of patients do develop strictures and patients can stilldevelop EAC Endoscopic therapy may include a combination of endoscopic mucosalresection of mucosal irregularities and photodynamic therapy of the entire segment ofBE

The patient has to weigh the risk of operative mortality and morbidity against theopportunity for cancer-free survival In contrast, the patient choosing endoscopic ther-apy balances the avoidance of procedural mortality and maintenance of esophageal func-

Figure 1-2 Management of HGD.

Patient