Contents. Part 1. Peritoneal Carcinomatosis: Basic Concepts

Transcription

1 Contents Part 1. Peritoneal Carcinomatosis: Basic Concepts 1. Structure and Function of Mesothelial Cells... 1 Introduction... 1 Structure of Mesothelial Cells... 1 Mesothelial Cell Functions... 3 Slippery Protective Layer... 3 Inflammation and Immune Response... 4 Tissue Repair... 6 Fibrin Regulation... 6 Role of Mesothelial Cells in Tumour Dissemination... 7 Cell Adhesion... 7 Cell Invasion Tumour Growth Summary and Conclusions References Molecular Biology of Peritoneal Carcinomatosis Introduction Peritoneal Tumour Dissemination Mesothelial Adhesion Mesothelial Invasion Stromal Invasion and Proliferation Tumour-Peritoneal Angiogenesis Summary References Role of Adhesion Molecules in Locoregional Cancer Spread The Micro-ecosystem of Peritoneal Carcinomatosis Homotypic Cell-Cell Adhesion by the Cadherins Heterotypic Cell-Cell and Cell-Matrix Adhesion by the Integrins Other Adhesion Compounds relevant for Peritoneal Carcinomatosis CD44 and Hyaluronate Sialyl Lewis and E-selectin CA 125 and Mesothelin L1 and Neuropilin Other Adhesion Molecules in the Peritoneum Conclusion and Future Perspectives Acknowledgements References... 45

2 X Contents 4. Surgical Trauma, Minimal Residual Disease and Locoregional Cancer Recurrence Introduction Minimal Residual Disease following Surgery Tumour Associated Factors Surgery Related Factors Tumour Seeding during Laparoscopy Postoperative Factors The Link between Residual Tumour Growth and Surgery The importance of Inflammation Surgery and Tumour Dormancy Prevention and Treatment of Residual Tumour Growth Prevention of Surgical Trauma Nonspecific Intraperitoneal Therapy Intraperitoneal Chemotherapy Inhibition of the Angiogenic Switch and Reversal of Tumour Dormancy.. 59 Inhibition of the Inflammatory Response Inhibition of Adhesion of Free Intraperitoneal Cancer Cells Summary and Conclusion References Pseudomyxoma Peritonei Syndrome: Classification of Appendiceal Mucinous Tumours Introduction Mucocele Mucosal Hyperplasia and Hyperplastic Polyp Serrated Adenoma (Mixed Hyperplastic-Adenomatous Polyp) Mucinous Adenoma (Mucinous Cystadenoma) Mucinous Neoplasm of Uncertain Malignant Potential (M-UMP) Mucinous Neoplasm of Low Malignant Potential (M-LMP) Adenocarcinoma (Mucinous, Intestinal, and Signet Ring Types) Goblet Cell and Tubular Carcinoids Pseudomyxoma Peritonei Syndrome Conclusion References The Pathogenesis of Malignant Ascites Introduction Anatomical and Physiological Considerations Anatomy of the Peritoneal Membrane The Peritoneal Lymphatic System Characteristics of Malignant Ascites - Intraperitoneal Protein Accumulation Impaired Drainage or Increased Production?

3 Contents XI Starling s law of Capillary Hemodynamics Increased Capillary Permeability Increased Filtration Surface Area Increased Hydraulic Pressure Difference Decreased Oncotic Pressure Difference Conclusion References Natural History of Peritoneal Carcinomatosis from Digestive Origin Introduction Aetiology of Peritoneal Carcinomatosis Clinical Features of Peritoneal Carcinomatosis from Digestive Origin Gastric Cancer Colorectal Cancer Pancreatic Cancer Cancer with Unknown Primary Natural History of Peritoneal Carcinomatosis Discussion References Part 2. The Rationale for Intraperitoneal Heat and Drug Therapy 8. Intraperitoneal Drug Therapy: Physical and Biological Principles Background IP Versus Systemic (IV) Chemotherapy Pharmacokinetic Advantage Compartmental Approach to IP Pharmacokinetics Distributed Model and Challenges of the Peritoneal Barrier in Neoplasms Anatomic Peritoneum Interstitium and Tumour Microenvironment Microcirculation Summary of Neoplastic versus Normal Peritoneal Barrier Importance of Contact Area to Intraperitoneal Chemotherapy Penetration of Antineoplastic Agents Intraperitoneal Chemotherapy with Small Molecular Weight Drugs Intraperitoneal Therapy with Macromolecular Agents Acknowledgment References Current Status of Intraperitoneal Antineoplastic Drug Delivery Intraperitoneal Chemotherapy: Historical Perspective The Dedrick Model and Pre-clinical Evaluation of Intraperitoneal Chemotherapy Penetration of Cytotoxic Antineoplastic Agents into Tumour Tissue

4 XII Contents Drug Delivery by Direct Penetration versus Capillary Flow Phase I Trial Experience with Intraperitoneal Antineoplastic Drug Delivery156 Phase II Trials of Intraperitoneal Antineoplastic Drug Delivery Phase III Trials of Cisplatin-based Intraperitoneal Chemotherapy as Primary Treatment of Advanced Ovarian Cancer Options for Use of Primary IP Chemotherapy of Ovarian Cancer Other Potential Uses of Intraperitoneal Antineoplastic Drug Delivery in the Management of Ovarian Cancer Randomized Trial Experience with Intraperitoneal Antineoplastic Drug Delivery in Non-ovarian Cancers References The Biologic Rationale of Hyperthermia Abstract Introduction Basic Principles of Hyperthermic Cell Death Molecular and Cellular Effectors of Hyperthermia Alterations of the Tumour Microenvironment Hyperthermia and the Immune System Cellular Immune Response Heat Shock Proteins Summary References Interactions between Hyperthermia and Cytotoxic Drugs Abstract Introduction Principles of heat-drug interaction Hyperthermia and drug resistance Pharmacological studies Heat interactions of novel compounds Summary References Pharmacodynamic Aspects of Intraperitoneal Cytotoxic Therapy Introduction General Pharmacodynamic Aspects of Intraoperative Intraperitoneal Chemotherapy Pharmacodynamics of Cytotoxic Drugs used with HIPEC Alkylating Drugs Platinum Compounds Topoisomerase Interactive Agents Antimetabolites Antimicrotubule Agents Approaches to Increase Tumour Drug Distribution Increasing Drug Supply

5 Contents XIII Enhancing Drug Penetration Summary and Conclusion References Part 3. Cytoreductive Surgery for Peritoneal Carcinomatosis: Techniques and Methods 13. Patient Selection for Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion Introduction Indications for Cytoreduction and HIPEC Pseudomyxoma Peritonei Colorectal Cancer Gastric Cancer Ovarian Cancer Peritoneal Mesothelioma Peritoneal Sarcomatosis Patient Selection Preoperative Imaging Repeat Operations References Staging and Scoring of Peritoneal Carcinomatosis Introduction Extent of Prior Surgery Prior Surgery Score (PSS) Extent and Distribution of Disease Carcinomatosis Staging by the Japanese Research Society for Gastric Cancer (P-Score) Japanese Research Society for Gastric Cancer P-Score Gilly Staging for Peritoneal Carcinomatosis Peritoneal Cancer Index (PCI) Simplified Peritoneal Cancer Index Involved Regions (N-score) Assessment of Completeness or Extent of Surgery Completeness of Cytoreduction Score Residual Disease (R) - Score Extent of Surgery Extent of Surgery Score Level of Cytoreduction Conclusion References

6 XIV Contents 15. Peritonectomy Procedures Introduction Electroevaporative surgery Patient Positioning Construction of the Surgical Field to provide Simultaneous Exposure of the Abdomen and Pelvis Parietal Peritoneal Stripping from the Anterior Abdominal Wall Stripping the Visceral Peritoneum from the Surface of the Bladder Parietal Peritoneal Dissection to the Paracolic Sulcus and Beyond Peritoneal Stripping from Beneath the Left Hemidiaphragm Greater Omentectomy and Splenectomy with Completion of the Left Subphrenic Peritonectomy Peritoneal Stripping from Beneath the Right Hemidiaphragm Removal of an Envelope of Tumour from Beneath the Right Hemidiaphragm, from the Right Subhepatic Space, and from the Surface of the Liver Completed Right Subphrenic Peritonectomy Cholecystectomy with Resection of the Hepatoduodenal Ligament Circumferential Resection of the Hepatogastric Ligament and Lesser Omentum by Digital Dissection Limits of the Lesser Omentectomy with Stripping of the Floor of the Omental Bursa Limits of the Complete Pelvic Peritonectomy Resection of Rectosigmoid Colon, Uterus, and Cul-de-sac of Douglas Preparation for Perioperative Intraperitoneal Chemotherapy Discussion References Continuous Peritoneal Perfusion: Techniques, Methods and Applications Introduction Methods of Hyperthermic Intraperitoneal Chemotherapy Open Perfusion Methods Partially Closed and Closed Perfusion Methods Safety Considerations for HIPEC Technical Parameters of Hyperthermic Chemoperfusion Cytostatic Agents Suitable for HIPEC Intraperitoneal Temperature Carrier solution Volume Duration Flow rate Conclusions References Handling of Chemotherapeutic Drugs in the OR: Hazards and Safety Considerations Introduction

7 Contents XV Exposure and Effect Studies Routes and mechanisms of exposure Inhalation of Airborne Compounds Ingestion and Eye Contact Skin Contact Injection through Accidental Injury with Sharp Tools Recommendations for Safety Precautions Organizational measures Use of Technical and Personal Protective Equipment Spill Management, Cleaning and Decontamination Protocols Proper Waste Handling and Disposal Information and Training Medical Surveillance and Monitoring References Part 4. Clinical Results of Surgery with or without Intraperitoneal Heated Drug Therapy 18. Results of Cytoreduction followed by HIPEC in Carcinomatosis of Colorectal Origin Introduction Surgery for Peritoneal Carcinomatosis of Colorectal Origin Prognostic Factors Completeness of Cytoreduction Extent of Disease before Surgery Other Prognostic Factors Complications of Surgery The Learning Curve of Cytoreduction with HIPEC Conclusion References HIPEC with Oxaliplatin in the Treatment of Peritoneal Carcinomatosis of Colorectal Origin Introduction Patient Eligibility and Surgical Procedures Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Results of a Phase I Study of HIPEC with Oxaliplatin Methods Results Conclusion Results of a Phase I Study with Oxaliplatin using Hypotonic Solutions Introduction Methods Results

8 XVI Contents Results of a Phase II Study of HIPEC with Oxaliplatin Patients and methods Results Discussion Conclusion Comparison of HIPEC with Oxaliplatin versus Standard Systemic Chemotherapy HIPEC group Standard Group Overall survival rates Discussion Phase I study of HIPEC combining Oxaliplatin and Irinotecan Methods Results Conclusion Relation between the Extent of Cytoreductive surgery and the Rate of Postoperative Hematological Toxicity Background Methods Results Conclusion Future Directions and Conclusion Aknowledgement References Clinical Results of Cytoreduction and HIPEC in Pseudomyxoma Peritonei Introduction Site of Origin of PMP Pathological Classification of Appendiceal Neoplasms Clinical Trials of Cytoreduction and Intraperitoneal Chemotherapy Conclusion References The Impact of Therapy in the Treatment of Pseudomyxoma Peritonei. 329 Introduction Memorial Sloan-Kettering Cancer Center Experience Methods Clinicopathologic Features Operative Results Long term overall survival Evaluating the Impact of Therapy for PMP References

9 Contents XVII 22. Clinical Results of Cytoreduction and HIPEC for Malignant Peritoneal Mesothelioma Introduction Results of Cytoreduction and HIPEC Summary References Cytoreduction and Intraperitoneal Chemotherapy for Carcinomatosis from Gastric Cancer Introduction Diagnosis of Peritoneal Carcinomatosis Results of Systemic Chemotherapy in the Treatment of PC of Gastric Origin Treatment of PC of Gastric Origin with Intraperitoneal Chemotherapy Perioperative Intraperitoneal Chemotherapy Neoadjuvant Intraperitoneal and Systemic Chemotherapy Hyperthermic Intraperitoneal Chemoperfusion Early Postoperative Intraperitoneal Chemotherapy Peritonectomy Procedures Conclusion References Cytoreduction and Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Ovarian Cancer Introduction Cytoreductive Surgery Hyperthermic Intraperitoneal Chemotherapy Intraperitoneal Chemotherapy Intraperitoneal Hyperthermic Chemotherapy Effects of HIPEC Refractory Ovarian Cancer Prognostic Factors Affecting Patient Survival Conclusion References The role of Neoadjuvant Chemotherapy versus Primary Surgery in the Management of Stage III Ovarian Cancer Introduction Primary Cytoreductive Surgery Biological basis of Cytoreductive Surgery Optimal versus Suboptimal Cytoreductive Surgery Variables influencing Cytoreductive Surgery Outcome of Cytoreductive Surgery FIGO Stage IV Disease Neoadjuvant Chemotherapy and Interval Cytoreduction Neoadjuvant Chemotherapy followed by Interval Cytoreduction after Suboptimal Primary Cytoreduction

10 XVIII Contents Neoadjuvant Chemotherapy followed by Interval Cytoreduction as an Alternative to Primary Cytoreduction Laparoscopy to select Patients for Neoadjuvant Chemotherapy References Morbidity and Quality of Life following Cytoreduction and HIPEC Introduction Morbidity and Mortality following Cytoreduction and HIPEC Milano National Cancer Institute Experience Bowel Complications following Cytoreduction and HIPEC Quality of Life following Cytoreduction and HIPEC References Detection and Treatment of Recurrent Disease after Cytoreduction and HIPEC Follow-up after Cytoreduction Treatment of Recurrent Disease References Part 5. Nonoperative and Multimodal Management of Peritoneal Carcinomatosis 28. Systemic Chemotherapy in Patients with Peritoneal Carcinomatosis from Colorectal Cancer Introduction Peritoneal Carcinomatosis in Trials of Systemic Chemotherapy Systemic Therapy with 5-Fluorouracil New cytotoxic drugs: Irinotecan and Oxaliplatin Oral Fluoropyrimidines Antibodies in Treatment of Colorectal Cancer Treatment strategy References Systemic Chemotherapy in patients with Peritoneal Carcinomatosis from Non Colorectal Origin Introduction Systemic Therapy Conclusion References The Role of Radiotherapy in the treatment of Peritoneal Carcinomatosis Introduction PC Originating from Gastrointestinal Cancers PC Originating from Gynaecological Cancers

11 Contents XIX PC Originating from Other Cancers Conclusions and Future Prospects for Radiotherapy - the Role of Intensity Modulated Arc Therapy References Medical and Palliative Management of Malignant Ascites Introduction Pathophysiology and Diagnosis Symptomatic Management by Paracentesis Symptomatic Management by Diuretics Symptomatic Management by Peritoneovenous Shunts New Treatments Management of Symptomatic Malignant Ascites References Part 6. Experimental Approaches 32. Targeted Intraabdominal Chemotherapy for Peritoneal Carcinomatosis Summary Intentions and Basic Concepts of Targeted Chemotherapy Clinical Experience Experimental Evidence Animals and Experimental Design Cell Culture and Tumour Cell Inoculation Intraperitoneal Treatment Assessment of Peritoneal Tumour spread, Tumour Growth and Response to Treatment Tumour Growth and Response to Treatment Discussion Perspectives References Immunotherapy of Peritoneal Carcinomatosis Immunological Defence Mechanisms of the Peritoneal Cavity Unspecific Immunotherapy/Cytokines Stimulation of Immunocompetent Cells by Defined Cytokines Antibody Constructs Summary References Intraperitoneal Photodynamic Therapy Introduction Mechanisms of PDT Mediated Cell Death Preclinical Studies of Intraperitoneal PDT

12 XX Contents Clinical Applications of Intraperitoneal PDT New Frontiers in Intraperitoneal PDT: Molecularly Targeted Therapy Summary and Conclusions References Intraperitoneal Gene Therapy Introduction Vectors Gene Therapy Strategies Targeting p53 tumour suppressor gene Targeting HER-2/neu proto-oncogene Other adenovirus based approaches Experimental Approaches Conclusion References Index

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