Adenocarcinoma of the Esophagogastric Junction (Recent Results in Cancer Research Book 182)

Among malignant tumors, adenocarcinomas of the esophagogastric junction show the highest increase in incidence over the past three decades in Western industrialized countries. Accordingly, much effort is being devoted to basic and translational research in order to combat this frequently deadly disease. This special volume, with contributions from experts in the field, covers all aspects of adenocarcinomas of the esophagogastric junction. Etiology, pathogenesis, classification, and clinical staging are discussed, and there is special emphasis on state of the art treatment techniques. The latter range from endoscopic mucosal resections or limited surgical resections for early cancers to multimodality treatment options for locally advanced tumors. Emerging quality issues in surgical management are also addressed. Detailed attention is paid to other important recent developments, including molecular response prediction in multimodality treatment and early metabolic response evaluation by PET and PET-CT during neoadjuvant treatment. The diagnosis of micrometastases and its potential impact on therapeutic strategies are explored, and the use of sentinel node technology is assessed. This volume will be of interest to all clinicians concerned with the diagnosis and management of this malignancy. ISBN-13: 978-3540705789 Adenocarcinoma of the Esophagogastric Junction (Recent Results in Cancer Research, Volume 182) 1 Front-matter 2 Title page 3 Copyright 4 Dedication 5 Preface 6 Contents 8 1: Epidemiology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third 14 1.1 Introduction 14 1.2 Demographics, Trends, and Geographic Variations of Adenocarcinoma of the Esophagus and EGJ 15 1.3 Age, Gender, and Race 17 1.4 Gastroesophageal Reflux Disease and ACE and EGJ 17 1.5 Barrett’s Esophagus and ACE and EGJ 18 1.6 Obesity 20 1.7 Additional Risk Factors for ACE and EGJ 22 1.7.1 Tobacco 22 1.7.2 Alcohol 22 1.7.3 Diet and Nutrition 22 1.7.4 Medications 23 1.7.5 Helicobacter pylori Infection 24 1.8 Summary 24 References 25 2: Clinical Classification Systems of Adenocarcinoma of the Esophagogastric Junction 31 2.1 Esophagogastric Junction 31 2.1.1 Introduction 31 2.1.2 Definition 31 2.1.3 Different Classification Systems 32 2.2 Classification of Adenocarcinoma of the EGJ Type I-III 33 2.2.1 Definition and Topographical Classification 33 2.2.2 Diagnosis 33 2.2.3 Biological and Clinical Variations 35 2.2.3.1 Lymphatic Metastasis 36 2.2.4 Surgical Consequences 37 2.3 Conclusions 38 References 38 3: Histopathologic Classification of Adenocarcinoma of the Esophagogastric Junction 41 3.1 Introduction 41 3.2 Definition of the Esophagogastric Junction 42 3.3 WHO Classification of Tumors of the Digestive System 43 3.3.1 General Principles 43 3.4 Histopathologic Subtypes 43 3.5 Precancerous Lesions and Histogenetic Aspects 43 3.6 Prognostic Aspects of Histopathologic Classification 45 3.7 UICC Classification and Grading 46 3.8 Histopathologic Regression Grading after Neoadjuvant Therapy 46 References 48 4: The Pathogenesis of Barrett’s Metaplasia and the Progression to Esophageal Adenocarcinoma 51 4.1 Introduction 51 4.2 Normal Esophageal Epithelium 52 4.3 Pathogenesis of Barrett’s Metaplasia 53 4.3.1 Development of Barrett’s Esophagus: Congenital vs. Acquired 53 4.3.2 Definition of Barrett’s Metaplasia 53 4.3.3 Gastroesophageal Reflux Disease 53 4.3.3.1 Pathophysiology 54 4.3.3.2 Role of Inflammation and Oxidative Stress 55 4.3.3.3 GERD-Related Factors 56 4.3.4 Cell of Origin of Barrett’s Metaplasia 59 4.3.4.1 Upward Migration of Gastric Epithelium 59 4.3.4.2 Transdifferentiation 59 4.3.4.3 Transitional Zone Theory 59 4.3.4.4 De-Novo Metaplasia 60 4.3.4.5 Duct Cell Metaplasia 60 4.3.4.6 Bone Marrow Stem Cells 60 4.3.5 Transformation into a Columnar Epithelium 61 4.3.6 Clonal Expansion 61 4.4 Progression to Esophageal Adenocarcinoma 62 4.4.1 Hallmarks of Cancer Progression 63 4.4.1.1 Self-Sufficiency in Growth 63 4.4.1.2 Insensitivity to Antigrowth Signals 64 4.4.1.3 Evading Apoptosis 64 4.4.1.4 Limitless Replicative Potential 64 4.4.1.5 Sustained Angiogenesis 65 4.4.1.6 Tissue Invasion and Dissemination 65 4.4.2 Genetic Instability 65 4.5 Summary 66 References 66 5: Differences in the Molecular Biology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third 76 5.1 Introduction 76 5.2 Microsatelite Instability (MSI) and Loss of Heterozygosity (LOH) 77 5.3 Difference in Phenotype on Histology and Immunohistochemistry 77 5.4 Differences in the Hallmarks of Cancer 78 5.5 Self-Sufficiency in Growth Signals 78 5.6 Insensitivity to Antigrowth Signals 78 5.7 Evasion of Apoptosis 79 5.8 Limitless Replicative Potential 79 5.9 Sustained Angiogenesis 79 5.10 Tissue Invasion 79 5.11 Conclusion 80 References 80 6: Clinical Staging of Adenocarcinoma of the Esophagogastric Junction 84 6.1 Introduction 84 6.2 Establishing the Diagnosis 84 6.3 The Tumor Center Localization Determines the Classification 85 6.4 Preoperative TNM Staging Defines Further Treatment Strategies 86 6.5 Imaging Techniques for AEG 86 6.6 Endoscopic Ultrasound (EUS) 86 6.7 Computed Tomography (CT) 88 6.8 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) 89 6.9 MRI 89 6.10 Staging Laparoscopy Excludes Peritoneal Disease 89 6.11 Conclusion 90 References 91 7: Endoscopic Mucosal Resection for Staging and Therapy of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric 95 7.1 Introduction 95 7.2 Staging and Marking Before ER 96 7.3 Endoscopic Resection Techniques 96 7.4Results of ER 97 7.5 Results in Early Barrett’s Adenocarcinoma or HGD 97 7.6 Complications of ER in Barrett Esophagus 98 7.7 ER for HGC or Early Cancer at the Esophagogastric Junction 98 7.8 ER for Gastric Neoplasia 99 7.9 Conclusion 99 References 99 8: Surgical Strategies for Adenocarcinoma of the Esophagogastric Junction 102 8.1 Introduction 102 8.2 Surgical Strategies for AEG Siewert Type I 104 8.2.1 Reconstruction 108 8.2.2 Limited Resection 108 8.2.3 Minimal Invasive Operation Techniques 109 8.3 Surgical Strategies for AEG Siewert Type II and III 110 8.3.1 Limited Resection 112 8.3.2 Minimal Invasive Techniques 112 8.3.3 Sentinel Node Technique 112 8.4 Summary 113 References 113 9: Current Status of Sentinel Lymph Node Biopsy in Adenocarcinoma of the Distal Esophagus, Gastric Cardia, and Proximal Stomach 116 9.1 Introduction 116 9.2 Pattern of Lymph Node Metastases 116 9.3 Extension of Resection 117 9.4 The Techniques of Sentinel Node Biopsy 117 9.5 Upstaging 119 9.6 Using the SLN as Frozen Section During Surgery 119 9.7 Current Status of Sentinel Lymph Node Biopsy in Gastric Cancer 119 9.8 Sentinel Lymph Node Concept in AEG 120 References 121 10: Current Diagnosis and Future Impact of Micrometastases for Therapeutic Strategies in Adenocarcinoma of the Esophagus, Ga 124 10.1 Introduction 124 10.2Incidence of Nodal Micrometastases 125 10.3Mode of Spread 126 10.4Effect of Nodal Microinvolvement on Survival 128 10.5Current and Future Perspectives 130 References 131 11: Quality Indicators of Surgery for Adenocarcinoma of the Esophagus and Gastroesophageal Junction 135 11.1 Introduction 135 11.2 Quality Issues in the Definition of Cancer of the Gastroesophageal Junction (GEJ) 136 11.3 Quality Control and Quality Issues in the Staging of Esophageal Cancer 138 11.4 Quality Issues in the Use and Indications for Induction Chemo- and Chemoradiotherapy 140 11.4.1 Chemotherapy 140 11.4.2 Chemoradiotherapy 141 11.5 Type of Surgical Approach, Extent of Esophageal/Gastric Resection, and Extent of Lymph Node Dissection 143 11.6 Use (and Misuse?) of Minimally Invasive Esophagectomy Techniques 145 11.7 Quality of Perioperative Management 146 11.8 Conclusion 147 References 147 12: Peri-Operative and Complication Management for Adenocarcinoma of the Oesophagus and Oesophagigastric Junction 151 12.1 Patient Selection and Evaluation 151 12.2 Pre-Operative Preparation 152 12.3 Anaesthesia 152 12.4 Operative Prophylaxis of Complications 153 12.5 Immediate Post-Operative Care 154 12.6 Surgical Complications 155 12.7 Management of Pulmonary Complications 156 12.8Postoperative Nutrition 157 12.9 Summary 157 References 158 13: Multimodality Therapy for Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third 162 13.1 Introduction 162 13.2 Multimodal Therapy 163 13.3 The Evidence-Base for Neoadjuvant and Adjuvant Approaches 163 13.3.1 Neoadjuvant Chemotherapy 163 13.3.2Neoadjuvant Chemoradiotherapy (Table 13.2) 165 13.3.3Postoperative Combination Therapy 167 13.4 New Combinations and Novel Agents 167 13.5 Conclusions 168 References 171 14: Metabolic Response Evaluation by PET During Neoadjuvant Treatment for Adenocarcinoma of the Esophagus and Esophagogastric 174 14.1 Response Evaluation 176 14.2 Response Evaluation by CT Scan Studies and EUS 177 14.3 Response Evaluation by PET After Neoadjuvant Treatment 178 14.4 PET During Treatment 180 14.5 Conclusion 181 References 182 15: Molecular Response Prediction in Multimodality Treatment for Adenocarcinoma of the Esophagus and Esophagogastric Junctio 185 15.1 Introduction 185 15.2 Molecular Markers; Defining their Role 186 15.2.1 Epidermal Growth Factor Receptors (EGFR, HER2/neu) 188 15.2.2 Tumor Suppressor Gene p53 188 15.2.3 Survivin 189 15.2.4 Cyclooxygenase-2 (COX-2) 189 15.2.5 Excision Repair Cross-Complementing 1 (ERCC1) 190 15.2.6 Gene Expression Microarray Profiling 190 15.2.7 CpG Island Methylator Phenotype (CIMP) 191 15.3 Conclusion 192 References 192 Front Matter....Pages i-xiv Epidemiology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third....Pages 1-17 Clinical Classification Systems of Adenocarcinoma of the Esophagogastric Junction....Pages 19-28 Histopathologic Classification of Adenocarcinoma of the Esophagogastric Junction....Pages 29-38 The Pathogenesis of Barrett’s Metaplasia and the Progression to Esophageal Adenocarcinoma....Pages 39-63 Differences in the Molecular Biology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third....Pages 65-72 Clinical Staging of Adenocarcinoma of the Esophagogastric Junction....Pages 73-83 Endoscopic Mucosal Resection for Staging and Therapy of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third....Pages 85-91 Surgical Strategies for Adenocarcinoma of the Esophagogastric Junction....Pages 93-106 Current Status of Sentinel Lymph Node Biopsy in Adenocarcinoma of the Distal Esophagus, Gastric Cardia, and Proximal Stomach....Pages 107-114 Current Diagnosis and Future Impact of Micrometastases for Therapeutic Strategies in Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third....Pages 115-125 Quality Indicators of Surgery for Adenocarcinoma of the Esophagus and Gastroesophageal Junction....Pages 127-142 Peri-Operative and Complication Management for Adenocarcinoma of the Oesophagus and Oesophagigastric Junction....Pages 143-153 Multimodality Therapy for Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third....Pages 155-166 Metabolic Response Evaluation by PET During Neoadjuvant Treatment for Adenocarcinoma of the Esophagus and Esophagogastric Junction....Pages 167-177 Molecular Response Prediction in Multimodality Treatment for Adenocarcinoma of the Esophagus and Esophagogastric Junction....Pages 179-191 Epidemiology Of Adenocarcinoma Of The Esophagus, Gastric Cardia, And Upper Gastric Third -- Clinical Classification Systems Of Adenocarcinoma Of The Esophagogastric Junction -- Histopathologic Classification Of Adenocarcinoma Of The Esophagogastric Junction -- The Pathogenesis Of Barrett's Metaplasia And The Progression To Esophageal Adenocarcinoma -- Differences In The Molecular Biology Of Adenocarcinoma Of The Esophagus, Gastric Cardia, And Upper Gastric Third -- Clinical Staging Of Adenocarcinoma Of The Esophagogastric Junction -- Endoscopic Mucosal Resection For Staging And Therapy Of Adenocarcinoma Of The Esophagus, Gastric Cardia, And Upper Gastric Third -- Surgical Strategies For Adenocarcinoma Of The Esophagogastric Junction -- Current Status Of Sentinel Lymph Node Biopsy In Adenocarcinoma Of The Distal Esophagus, Gastric Cardia, And Proximal Stomach -- Current Diagnosis And Future Impact Of Micrometastases For Therapeutic Strategies In Adenocarcinoma Of The Esophagus, Gastric Cardia, And Upper Gastric Third -- Quality Indicators Of Surgery For Adenocarcinoma Of The Esophagus And Gastroesophageal Junction -- Peri-operative And Complication Management For Adenocarcinoma Of The Oesophagus And Oesophagigastric Junction -- Multimodality Therapy For Adenocarcinoma Of The Esophagus, Gastric Cardia, And Upper Gastric Third -- Metabolic Response Evaluation By Pet During Neoadjuvant Treatment For Adenocardinoma Of The Esophagus And Esophagogastric Junction -- Molecular Response Prediction In Multimodality Treatment For Adenocarcinoma Of The Esophagus And Esophagogastric Junction. Paul M. Schneider, Ed. Includes Bibliographical References. Annotation Among malignant tumors, adenocarcinomas of the esophagogastric junction show the highest increase in incidence over the past three decades in Western industrialized countries. This special volume, with contributions from experts in the field, covers all aspects of the disease. Etiology, pathogenesis, classification, and clinical staging are discussed, and there is special emphasis on state of the art treatment techniques. The latter range from endoscopic mucosal resections or limited surgical resections for early cancers to multimodality treatment options for locally advanced tumors. Emerging quality issues in surgical management are addressed. Detailed attention is also paid to other important recent developments, including molecular response prediction, early metabolic response evaluation by PET and PET-CT, the diagnosis of micrometastases, and the use of sentinel node technology. This volume will be of interest to all clinicians concerned with the diagnosis and management of this malignancy La 4ème de couverture porte : "This special volume [...] covers all aspects of adenocarcinomas of the esophagogastric junction. Etiology, pathogenesis, classification, and clinical staging are discussed, and there is special emphasis on state of the art treatment techniques. The latter range from endoscopic mucosal resections or limited surgical resections for early cancers to multimodality treatment options for locally advanced tumors. Emerging quality issues in surgical management are also addressed. Detailed attention is paid to other important recent developments, including molecular response prediction in multimodality treatment and early metabolic response evaluation by PET and PET-CT during neoadjuvant treatment. The diagnosis of micrometastases and its potential impact on therapeutic strategies are explored, and the use of sentinel node technology is assessed."