Recent Results in Cancer Research

Transcription

1 Recent Results in Cancer Research 182 Managing Editors P.M. Schlag, Berlin H.-J. Senn, St. Gallen Associate Editors P. Kleihues, Zürich F. Stiefel, Lausanne B. Groner, Frankfurt A. Wallgren, Göteborg Founding Editor P. Rentchnik, Geneva

2 Paul M. Schneider (Ed.) Adenocarcinoma of the Esophagogastric Junction 1 3

3 Editor Prof. Dr. Paul M. Schneider Department of Surgery University Hospital Zurich Raemistrasse Zurich Switzerland ISBN: e-isbn: DOI: / Springer Heidelberg Dordrecht London New York Library of Congress Control Number: Springer-Verlag Berlin Heidelberg 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: estudio Calamar Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (

4 To my teacher J. Rüdiger Siewert, Emeritus Professor and Chairman, Department of Surgery, Technische Universität München, Germany, for his 70th birthday Zurich, Switzerland Paul M. Schneider, MD Professor of Surgery

5 Preface The Siewert Lesson for Adenocarcinomas of the Esophagogastric Junction: A Plea for an Order in a Complex Disease Adenocarcinomas of the esophagogastric (AEG) junction show an alarming increase in incidence over the last decades in Western industrialized countries. This special volume with contributions from dedicated individuals and friends in the field tries to summarize our current understanding of the etiology, pathogenesis, classification, clinical staging, and state-of-the-art treatment of this modern plague. In 1987, JR Siewert, Emeritus Professor and Chairman of the Department of Surgery (Fig.) at the Technische Universität München, Germany, inaugurated a therapeutically relevant classification of AEG which is used by many experts and recommended by the International Society for Diseases of the Esophagus and International Gastric Cancer Association. As St. Thomas of Aquino wrote in his Summa contra Gentiles (Book I, Chap. 1): Those ones have to be called wise who put the things into the right order (author s translation). The Siewert Classification is purely based on the anatomic localization of the tumor center, which can be defined by endoscopy using the proximal end of the longitudinal gastric mucosa folds as a pragmatic reference for the endoscopic cardia. AEG include all tumors 5 cm proximal (+5 cm) and distal ( 5 cm) of the endoscopic cardia (point zero). An adenocarcinoma of the distal esophagus (>1 to +5 cm), which usually arises from an area of specialized intestinal metaplasia (Barrett s esophagus) is classified as a type I cancer. A type II cancer is a true carcinoma of the cardia (+1 to 2 cm) arising at the esophagogastric junction, whereas a type III cancer ( 2 to 5 cm) is a subcardial gastric carcinoma that infiltrates the esophagogastric junction or the distal esophagus from below. It is noteworthy to mention that the new seventh UICC/AJCC TNM Classification, effective since January 2010, classifies AEG as one group of cancers and finally eliminates meanders like staging regional lymph node metastases at the celiac trunk for Barrett s cancer as systemic metastases (M1a). Even more important is that the new UICC classification of AEG neither eliminates the Siewert classification nor intends to suggest a change in the surgical approach to treat AEG. For Siewert type I cancers, the standard approach is a transthoracic en bloc esophagectomy with a two-field lymphadenectomy and for the majority of AEG type II and vii

6 viii Preface especially III, a transhiatally extended (i.e., distal esophageal resection) gastrectomy with lymphadenectomy of the lower mediastinum and a systematic abdominal D2- lymphadenectomy is adequate. However, surgeons dealing with type II and III cancers must be prepared to extend a planned transhiatally extended gastrectomy into a transhiatal or transthoracic esophagectomy in case of a positive resection margin at frozen section or if the situation clearly demands an esophagectomy or even esophagogastrectomy. Local tumor control is still the key to survival and can be achieved by an armada of stage-dependent techniques in experienced centers including endosopic mucosal resections and limited surgical resections for early cancers. For locally advanced tumors, multimodality therapy options are necessary treatment extensions not competing with, but rather amplifying surgical resections. As a consequence of differentiated diagnostic and therapeutic tools, emerging quality issues involving all aspects of AEG treatment can no longer be neglected, and these patients have to be treated in specialized centers. Recent developments from molecular pathogenesis to molecular response prediction and early metabolic response evaluation by PET-CT in neoadjuvant treatment protocols as well as sentinel node technology and micrometastases complete our current scientific understanding and efforts in basic and translational research to combat a frequently deadly disease. We have tried hard to summarize the major aspects of our current understanding of the etiology, pathogenesis, diagnosis, and treatment of a complex disease. At the end, we all should not forget Sepp Herberger s (Coach of the German Football World Champion Team 1954) words: After the game is before the game. Zurich Switzerland Paul Magnus Schneider, M.D. Professor of Surgery Fig. JR Siewert, Emeritus Professor and Chairman of the Department of Surgery at the Technische Universität, Munich, Germany

7 Contents 1 Epidemiology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third... 1 Manuel Vial, Luis Grande, and Manuel Pera 1.1 Introduction Demographics, Trends, and Geographic Variations of Adenocarcinoma of the Esophagus and EGJ Age, Gender, and Race Gastroesophageal Reflux Disease and ACE and EGJ Barrett s Esophagus and ACE and EGJ Obesity Additional Risk Factors for ACE and EGJ Tobacco Alcohol Diet and Nutrition Medications Helicobacter pylori Infection Summary References Clinical Classification Systems of Adenocarcinoma of the Esophagogastric Junction Stefan Paul Mönig and Arnulf H. Hölscher 2.1 Esophagogastric Junction Introduction Definition Different Classification Systems Classification of Adenocarcinoma of the EGJ Type I-III Definition and Topographical Classification Diagnosis Biological and Clinical Variations ix

8 x Contents Surgical Consequences Conclusions References Histopathologic Classification of Adenocarcinoma of the Esophagogastric Junction Stephan E. Baldus 3.1 Introduction Definition of the Esophagogastric Junction WHO Classification of Tumors of the Digestive System General Principles Histopathologic Subtypes Precancerous Lesions and Histogenetic Aspects Prognostic Aspects of Histopathologic Classification UICC Classification and Grading Histopathologic Regression Grading After Neoadjuvant therapy References The Pathogenesis of Barrett s Metaplasia and the Progression to Esophageal Adenocarcinoma Brechtje A. Grotenhuis, J. Jan B. van Lanschot, Winand N.M. Dinjens, and Bas P.L. Wijnhoven 4.1 Introduction Normal Esophageal Epithelium Pathogenesis of Barrett s Metaplasia Development of Barrett s Esophagus: Congenital vs. Acquired Definition of Barrett s Metaplasia Gastroesophageal Reflux Disease Cell of Origin of Barrett s Metaplasia Transformation into a Columnar Epithelium Clonal Expansion Progression to Esophageal Adenocarcinoma Hallmarks of Cancer Progression Genetic Instability Summary References Differences in the Molecular Biology of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third Kuno Lehmann and Paul M. Schneider 5.1 Introduction Microsatelite Instability (MSI) and Loss of Heterozygosity (LOH)... 66

9 Contents xi 5.3 Difference in Phenotype on Histology and Immunohistochemistry Differences in the Hallmarks of Cancer Self-Sufficiency in Growth Signals Insensitivity to Antigrowth Signals Evasion of Apoptosis Limitless Replicative Potential Sustained Angiogenesis Tissue Invasion Conclusion References Clinical Staging of Adenocarcinoma of the Esophagogastric Junction Julia Cordin, Kuno Lehmann, and Paul M. Schneider 6.1 Introduction Establishing the Diagnosis The Tumor Center Localization Determines the Classification Preoperative TNM Staging Defines Further Treatment Strategies Imaging Techniques for AEG Endoscopic Ultrasound (EUS) Computed Tomography (CT) Fluorodeoxyglucose Positron Emission Tomography ( 18 FDG-PET) MRI Staging Laparoscopy Excludes Peritoneal Disease Conclusion References Endoscopic Mucosal Resection for Staging and Therapy of Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third Henriette Heinrich and Peter Bauerfeind 7.1 Introduction Staging and Marking Before ER Endoscopic Resection Techniques Results of ER Results in Early Barrett s Adenocarcinoma or HGD Complications of ER in Barrett Esophagus ER for HGC or Early Cancer at the Esophagogastric Junction ER for Gastric Neoplasia Conclusion References

10 xii Contents 8 Surgical Strategies for Adenocarcinoma of the Esophagogastric Junction Marc Schiesser and Paul M. Schneider 8.1 Introduction Surgical Strategies for AEG Siewert Type I Reconstruction Limited Resection Minimal Invasive Operation Techniques Surgical Strategies for AEG Siewert Type II and III Limited Resection Minimal Invasive Techniques Sentinel Node Technique Summary References Current Status of Sentinel Lymph Node Biopsy in Adenocarcinoma of the Distal Esophagus, Gastric Cardia, and Proximal Stomach Stephan Gretschel and Peter M. Schlag 9.1 Introduction Pattern of Lymph Node Metastases Extension of Resection The Techniques of Sentinel Node Biopsy Upstaging Using the SLN as Frozen Section During Surgery Current Status of Sentinel Lymph Node Biopsy in Gastric Cancer Sentinel Lymph Node Concept in AEG References Current Diagnosis and Future Impact of Micrometastases for Therapeutic Strategies in Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third Asad Kutup, Emre F. Yekebas, and Jakob R. Izbicki 10.1 Introduction Incidence of Nodal Micrometastases Mode of Spread Effect of Nodal Microinvolvement on Survival Current and Future Perspectives References

11 Contents xiii 11 Quality Indicators of Surgery for Adenocarcinoma of the Esophagus and Gastroesophageal Junction Toni Lerut, Georges Decker, Willy Coosemans, Paul De Leyn, Herbert Decaluwé, Philippe Nafteux, and Dirk Van Raemdonck 11.1 Introduction Quality Issues in the Definition of Cancer of the Gastroesophageal Junction (GEJ) Quality Control and Quality Issues in the Staging of Esophageal Cancer Quality Issues in the Use and Indications for Induction Chemo- and Chemoradiotherapy Chemotherapy Chemoradiotherapy Type of Surgical Approach, Extent of Esophageal/Gastric Resection, and Extent of Lymph Node Dissection Use (and Misuse?) of Minimally Invasive Esophagectomy Techniques Quality of Perioperative Management Conclusion References Peri-Operative and Complication Management for Adenocarcinoma of the Oesophagus and Oesophagigastric Junction K. Tobias E. Beckurts 12.1 Patient Selection and Evaluation Pre-Operative Preparation Anaesthesia Operative Prophylaxis of Complications Immediate Post-Operative Care Surgical Complications Management of Pulmonary Complications Postoperative Nutrition Summary References Multimodality Therapy for Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third John V. Reynolds, Thomas J. Murphy, and Narayamasamy Ravi 13.1 Introduction Multimodal Therapy The Evidence-Base for Neoadjuvant and Adjuvant Approaches

12 xiv Contents Neoadjuvant Chemotherapy Neoadjuvant Chemoradiotherapy Postoperative Combination Therapy New Combinations and Novel Agents Conclusions References Metabolic Response Evaluation by PET During Neoadjuvant Treatment for Adenocarcinoma of the Esophagus and Esophagogastric Junction A. Sendler 14.1 Response Evaluation Response Evaluation by CT Scan Studies and EUS Response Evaluation by PET After Neoadjuvant Treatment PET During Treatment Conclusion References Molecular Response Prediction in Multimodality Treatment for Adenocarcinoma of the Esophagus and Esophagogastric Junction Georg Lurje and Heinz-Josef Lenz 15.1 Introduction Molecular Markers; Defining their Role Epidermal Growth Factor Receptors (EGFR, HER2/neu) Tumor Suppressor Gene p Survivin Cyclooxygenase-2 (COX-2) Excision Repair Cross-Complementing 1 (ERCC1) Gene Expression Microarray Profiling CpG Island Methylator Phenotype (CIMP) Conclusion References