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
