Esophageal Cancer and Barrett's Esophagus

PROFESSOR PRATEEK SHARMA, Professor Medicine, University of Kansas School of Medicine and Veterans Affairs Medical Center, Kansas City, Missouri, and Southern Arizona Veterans Affairs Health Care System and Arizona Health Sciences Center, Tucson, Arizona, USA. PROFESSOR RICHARD SAMPLINER, Professor of Medicine at the University of Arizona, Tucson, AZ, USA, and Chief of Gastroenterology at the Southern Arizona VA Health Care System. DAVID ILSON, MD, PHD, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

List of contributors ix

Preface xiii

1 Epidemiology of esophageal carcinoma 1
Mohammad H. Shakhatreh and Hashem B El-Serag

1.1 The incidence and mortality related to esophageal cancer 1

1.2 Mortality 2

1.3 Risk factors for EA 2

2 Barrett's esophagus: definition and diagnosis 15
Stuart Jon Spechler

2.1 Introduction 15

2.2 Early history of Barrett's esophagus 15

2.3 Early reports on the histology of Barrett's esophagus 16

2.4 Identification of the gastroesophageal junction 16

2.5 Recognition of short segment Barrett's esophagus 17

2.6 Intestinal metaplasia and adenocarcinoma of the esophagus 18

2.7 The problem of cardiac mucosa 18

2.8 Definition of Barrett's esophagus 19

2.9 Diagnostic criteria for Barrett's esophagus 19

2.10 Intestinal metaplasia at the GEJ 20

3 Epidemiology and prevalence of Barrett's esophagus 25
Helen G. Coleman, Shivaram K. Bhat and Liam J. Murray

3.1 Introduction 25

3.2 BE prevalence 25

3.3 BE incidence 28

3.4 Etiology and risk factors for BE 30

3.5 Neoplastic progression risk in BE 30

3.6 Conclusions 31

4 Esophageal adenocarcinoma: risk factors 35
Mariam Naveed and Kerry B. Dunbar

4.1 Introduction 35

4.2 Gastroesophageal reflux disease (GERD) 35

4.3 Barrett's esophagus (BE) 36

4.4 Obesity 37

4.5 Smoking 37

4.6 Alcohol 38

4.7 Dietary factors 38

4.8 Medication use 38

4.9 H. pylori 39

4.10 Demographics 39

4.11 Summary 39

5 Esophageal motility abnormalities in Barrett's esophagus 45
Kumar Krishnan, John E. Pandolfino and Peter J. Kahrilas

5.1 Introduction 45

5.2 Antireflux barrier 45

5.3 Lower esophageal sphincter 46

5.4 Diaphragmatic sphincter and hiatal hernia 46

5.5 Mechanical properties of the relaxed EGJ 47

5.6 Esophageal clearance 48

5.7 Peristaltic dysfunction 49

5.8 Gastric emptying and duodenogastroesophageal reflux 49

5.9 Therapy of motor abnormalities in Barrett's esophagus 50

5.10 Conclusion 50

6 Molecular biology of Barrett's esophagus and esophageal adenocarcinoma 55
Ayesha Noorani and Rebecca C. Fitzgerald

6.1 Introduction 55

6.2 Genetic and host susceptibility 55

6.3 Environmental factors contributing to the development of BE 57

6.4 Genomic instability mutations and copy number changes in candidate genes 58

6.5 The advent of next generation sequencing 61

6.6 Future directions and conclusions 63

7 Histology of Barrett's esophagus: metaplasia and dysplasia 69
Deepa T. Patil and John R. Goldblum

7.1 Introduction 69

7.2 Normal anatomy and histology 69

7.3 Histology of Barrett's esophagus 69

7.4 Intestinal metaplasia of the EGJ 71

7.5 Barrett's esophagus-related dysplasia 71

7.6 Intramucosal adenocarcinoma (IMC) 72

7.7 Submucosal adenocarcinoma 73

7.8 Morphologic types of dysplasia 73

7.9 Sampling error and observer variation in Barrett's esophagus-related dysplasia 74

7.10 Surrogate biomarkers for assessing risk of esophageal adenocarcinoma 74

8 Helicobacter pylori and esophageal neoplasia 79
Arne Kandulski, Marino Venerito and Peter Malfertheiner

8.1 Introduction 79

8.2 H. pylori infection -- gastritis pattern and gastric physiology with impact on gastroesophageal reflux disease 79

8.3 Epidemiological studies -- GERD symptoms, erosive esophagitis and H. pylori 80

8.4 H. pylori, Barrett's esophagus and esophageal adenocarcinoma 81

8.5 H. pylori eradication and GERD 82

8.6 H. pylori and esophageal squamous cell carcinoma 83

8.7 Conclusions 84

9 Screening and surveillance 87
Sarmed S. Sami and Krish Ragunath

9.1 Introduction 87

9.2 Screening 87

9.3 Surveillance 90

9.4 Conclusion 93

10 New surface imaging technologies for dysplasia and cancer detection 97
 David F. Boerwinkel, Wouter L. Curvers and Jacques J.G.H.M. Bergman

10.1 Introduction 97

10.2 Surface imaging in Barrett's esophagus 98

10.3 Surface imaging for esophageal squamous cell carcinoma 103

10.4 Summary 104

11 New cellular imaging technologies for dysplasia and cancer detection 107
Helmut Neumann and Ralf Kiesslich

11.1 Introduction 107

11.2 Confocal laser endomicroscopy 107

11.3 Endocytoscopy 110

11.4 Optical coherence tomography 111

11.5 Molecular imaging in Barrett's 112

11.6 Conclusion 112

12 The role of endoscopic ultrasound in esophageal cancer 115
Samad Soudagar and Neil Gupta

12.1 Background 115

12.2 Equipment 115

12.3 Visualized EUS anatomy 115

12.4 Obstacles to accurate EUS staging 116

12.5 Esophageal cancer staging and impact on treatment intervention 117

12.6 T staging 117

12.7 N staging 119

12.8 M staging 120

12.9 Restaging after chemoradiotherapy and surveillance for disease recurrence 120

12.10 Conclusion/summary 121

13 Staging of esophageal adenocarcinoma by CT, PET, and other modalities 125
Florian Lordick, Katja Ott, Matthias Ebert, Lars Grenacher, Bernd-Joachim Krause and Christian Wittekind

13.1 Introduction 125

13.2 Endoscopic staging 125

13.3 Staging by external ultrasonography 128

13.4 Staging by radiological examinations 128

13.5 Staging by positron emission tomography (PET) 129

13.6 The value of FDG-PET to predict response to pre-operative treatment 130

13.7 Conclusion: summary of recommended staging procedures 132

14 Medical management of Barrett's esophagus 137
Sachin Wani

14.1 Introduction 137

14.2 Assessment of symptoms 137

14.3 Acid suppressive therapies in management of reflux symptoms 138

14.4 Normalization of intraesophageal acid exposure 138

14.5 Management of erosive esophagitis 139

14.6 Maintenance of healed mucosa after endoscopic eradication therapies 139

14.7 Conclusions 140

15 Thermal therapies and photodynamic therapy for early esophageal neoplasia 143
Jacques Deviere

15.1 Introduction 143

15.2 Photodynamic therapy 144

15.3 Argon plasma coagulation 144

15.4 Cryotherapy 147

15.5 Conclusion 147

16 RFA for early esophageal neoplasia 151
 Daniel K. Chan, Cadman L. Leggett and Kenneth K. Wang

16.1 Background 151

16.2 Device and procedural technique 151

16.3 Efficacy and durability of radiofrequency ablation 154

16.4 Initial treatment response to RFA and risk factors for failed ablation 156

16.5 Endoscopic mucosal resection in combination with radiofrequency ablation 157

16.6 Safety and tolerability of radiofrequency ablation 157

16.7 Subsquamous intestinal metaplasia after radiofrequency ablation 157

16.8 Surveillance following radiofrequency ablation 158

16.9 Conclusions 158

17 The role of endoscopic cryotherapy for treatment and palliation 161
Kristle Lee Lynch, Eun Ji Shin and Marcia Irene Canto

17.1 Introduction 161

17.2 Cryotherapy mechanisms of tissue injury 161

17.3 Types of cryotherapy: devices, dosing, and endoscopic application 162

17.4 Efficacy and safety in Barrett's esophagus 164

17.5 Cryotherapy for the treatment of esophageal carcinoma 166

17.6 Summary and future directions 167

18 Endoscopic resection 169
Oliver Pech

18.1 Introduction 169

18.2 ER techniques 169

18.3 ER in HGIN and early Barrett's cancer 171

18.4 ER of submucosal Barrett's adenocarcinoma 174

18.5 Conclusions 174

19 Endoscopic submucosal dissection 177
Hironori Yamamoto, Tsuneo Oyama and Takuji Gotoda

19.1 Introduction 177

19.2 Indications of ESD for esophageal cancer 177

19.3 Preoperative examination 178

19.4 Techniques of ESD [19--22] for esophageal cancer 178

19.5 Complications 184

19.6 Sedation and anesthesia 185

19.7 Results 185

19.8 Training 185

19.9 Conclusion 186

20 Surgical therapy of early esophageal cancer 189
Toshitaka Hoppo and Blair A. Jobe

20.1 Introduction 189

20.2 "Early" esophageal cancer 189

20.3 Indication of surgical resection for early esophageal adenocarcinoma 190

20.4 Strategy of surgical resection for early esophageal adenocarcinoma 190

20.5 Choice of surgical approach and outcomes 191

20.6 Discussion 194

20.7 Conclusion 195

21 Chemoprevention: can we prevent esophageal cancer? 199
Janusz Jankowski and Mary Denholm

21.1 Overview 199

21.2 The effect of aspirin on cancer prevention 200

21.3 Risks and adverse effects of aspirin 201

21.4 The role of aspirin in reflux disease 203

21.5 Risk-benefits of aspirin 204

21.6 AspECT trial 205

22 Selection of patients for cancer prevention and eradication 209
Aaron J. Small and Gary W. Falk

22.1 Introduction 209

22.2 Patient factors 209

22.3 Cancer risk and grade of dysplasia 210

22.4 Baseline quality measures 212

22.5 The lesion 213

22.6 Predictors of response 215

22.7 Predictors of initial response to therapy 215

22.8 Future considerations 217

22.9 Conclusions 217

23 Combined modality therapy in locally advanced esophageal cancer 221
Geoffrey Y. Ku and David H. Ilson

23.1 Introduction 221

23.2 Pre-operative chemotherapy 221

23.3 Post-operative therapy 222

23.4 Chemoradiation for medically inoperably patients 224

23.5 Pre-operative chemoradiation 224

23.6 Pre-operative chemoradiation vs. chemotherapy 225

23.7 Definitive vs. pre-operative chemoradiation 225

23.8 Newer chemoradiation regimens 226

23.9 Targeted therapies 226

23.10 Positron emission tomography-directed therapy 227

23.11 Conclusion 228

24 Surgery in locally advanced esophageal cancer 231
Nabil Rizk

24.1 Introduction 231

24.2 Chemotherapy, chemoradiation and surgical complications 231

24.3 Technical considerations 232

24.4 Risks of salvage surgery 233

24.5 Conclusion 234

25 Radiation therapy for locally advanced esophageal cancer 237
Heath D. Skinner and Bruce D. Minsky

25.1 Introduction 237

25.2 Definitive therapy in unresectable locally advanced esophageal cancer 237

25.3 Trimodality therapy 240

25.4 Techniques of radiation therapy 243

25.5 Conclusions 245

26 Systemic therapy and targeted agents in advanced esophageal cancer 251
Mark A. Lewis and Harry H. Yoon

26.1 Introduction 251

26.2 Chemotherapy 251

26.3 Targeted therapy 253

26.4 Future directions 258

26.5 Conclusions 259

27 Role of endoscopy and nutritional support in advanced esophageal cancer 265
Manol Jovani, Andrea Anderloni and Alessandro Repici

27.1 Introduction 265

27.2 Nutritional support in advanced esophageal cancer 266

27.3 Palliative endoscopy in inoperable esophageal cancer 266

27.4 Conclusion 273

Index 277