Peritoneal Carcinomatosis: A Multidisciplinary Approach (eBook)

Foreword 5
Preface 7
Contents 9
List of Contributors 21
Structure and Function of Mesothelial Cells 32
Introduction 32
Structure of Mesothelial Cells 32
Mesothelial Cell Functions 34
Role of Mesothelial Cells in Tumour Dissemination 38
Summary and Conclusions 43
References 43
Molecular Biology of Peritoneal Carcinomatosis 51
Introduction 51
Peritoneal Tumour Dissemination 52
Mesothelial Adhesion 52
Mesothelial Invasion 54
Stromal Invasion and Proliferation 57
Tumour-Peritoneal Angiogenesis 60
Summary 60
References 61
Role of Adhesion Molecules in Locoregional Cancer Spread 64
The Micro-ecosystem of Peritoneal Carcinomatosis 64
Homotypic Cell-Cell Adhesion by the Cadherins 66
Heterotypic Cell-Cell and Cell-Matrix Adhesion by the Integrins 69
Other Adhesion Compounds relevant for Peritoneal Carcinomatosis 71
Conclusion and Future Perspectives 73
Acknowledgements 74
References 74
Surgical Trauma, Minimal Residual Disease and Locoregional Cancer Recurrence 79
Introduction 79
Minimal Residual Disease following Surgery 79
The Link between Residual Tumour Growth and Surgery 83
Prevention and Treatment of Residual Tumour Growth 86
Summary and Conclusion 88
References 89
Pseudomyxoma Peritonei Syndrome: Classification of Appendiceal Mucinous Tumours 98
Introduction 98
‘Mucocele’ 98
Mucosal Hyperplasia and Hyperplastic Polyp 99
Serrated Adenoma (Mixed Hyperplastic-Adenomatous Polyp) 101
Mucinous Adenoma (Mucinous Cystadenoma) 102
Mucinous Neoplasm of Uncertain Malignant Potential ( M- UMP) 106
Mucinous Neoplasm of Low Malignant Potential (M-LMP) 108
Adenocarcinoma (Mucinous, Intestinal, and Signet Ring Types) 113
Goblet Cell and Tubular Carcinoids 116
‘Pseudomyxoma Peritonei Syndrome’ 119
Conclusion 129
References 130
The Pathogenesis of Malignant Ascites 135
Introduction 135
Anatomical and Physiological Considerations 135
Characteristics of Malignant Ascites - Intraperitoneal Protein Accumulation 137
Impaired Drainage or Increased Production? 137
Starling’s law of Capillary Hemodynamics 138
Conclusion 141
References 141
Natural History of Peritoneal Carcinomatosis from Digestive Origin 145
Introduction 145
Aetiology of Peritoneal Carcinomatosis 145
Clinical Features of Peritoneal Carcinomatosis from Digestive Origin 146
Discussion 153
References 154
Intraperitoneal Drug Therapy: Physical and and Biological Principles 156
Background 156
IP Versus Systemic (IV) Chemotherapy 157
Distributed Model and Challenges of the Peritoneal Barrier in Neoplasms 160
Importance of Contact Area to Intraperitoneal Chemotherapy 166
Penetration of Antineoplastic Agents 167
Acknowledgment 170
References 170
Current Status of Intraperitoneal Antineoplastic Drug Delivery 178
Intraperitoneal Chemotherapy: Historical Perspective 178
The “Dedrick Model” and Pre-clinical Evaluation of Intraperitoneal Chemotherapy 178
Penetration of Cytotoxic Antineoplastic Agents into Tumour Tissue 179
Phase I Trial Experience with Intraperitoneal Antineoplastic Drug Delivery 181
Phase II Trials of Intraperitoneal Antineoplastic Drug Delivery 182
Phase III Trials of Cisplatin-based Intraperitoneal Chemotherapy as Primary Treatment of Advanced Ovarian Cancer 184
Options for Use of Primary IP Chemotherapy of Ovarian Cancer 186
Other Potential Uses of Intraperitoneal Antineoplastic Drug Delivery in the Management of Ovarian Cancer 187
Randomized Trial Experience with Intraperitoneal Antineoplastic Drug Delivery in Non- ovarian Cancers 187
References 188
The Biologic Rationale of Hyperthermia 195
Abstract 195
Introduction 195
Basic Principles of Hyperthermic Cell Death 198
Molecular and Cellular Effectors of Hyperthermia 200
Alterations of the Tumour Microenvironment 201
Hyperthermia and the Immune System 202
Summary 204
References 204
Interactions between Hyperthermia and Cytotoxic Drugs 209
Abstract 209
Introduction 209
Principles of heat-drug interaction 211
Hyperthermia and drug resistance 212
Pharmacological studies 213
Heat interactions of novel compounds 213
Summary 214
References 215
Pharmacodynamic Aspects of Intraperitoneal Cytotoxic Therapy 218
Introduction 218
General Pharmacodynamic Aspects of Intraoperative Intraperitoneal Chemotherapy 218
Pharmacodynamics of Cytotoxic Drugs used with HIPEC 220
Approaches to Increase Tumour Drug Distribution 228
Summary and Conclusion 230
References 230
Patient Selection for Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion 238
Introduction 238
Indications for Cytoreduction and HIPEC 239
Patient Selection 243
Preoperative Imaging 245
Repeat Operations 247
References 248
Staging and Scoring of Peritoneal Carcinomatosis 253
Introduction 253
Extent of Prior Surgery 254
Extent and Distribution of Disease 255
Assessment of Completeness or Extent of Surgery 261
Extent of Surgery 263
Conclusion 264
References 265
Peritonectomy Procedures 269
Introduction 269
Electroevaporative surgery 269
Discussion 285
References 286
Continuous Peritoneal Perfusion: Techniques, Methods and Applications 287
Introduction 287
Methods of Hyperthermic Intraperitoneal Chemotherapy 287
Open Perfusion Methods 288
Partially Closed and Closed Perfusion Methods 289
Safety Considerations for HIPEC 291
Technical Parameters of Hyperthermic Chemoperfusion 292
Conclusions 294
References 294
Handling of Chemotherapeutic Drugs in the OR: Hazards and Safety Considerations 296
Introduction 296
Exposure and Effect Studies 297
Routes and mechanisms of exposure 298
Recommendations for Safety Precautions 300
Organizational measures 301
References 307
Results of Cytoreduction followed by HIPEC in Carcinomatosis of Colorectal Origin 312
Introduction 312
Surgery for Peritoneal Carcinomatosis of Colorectal Origin 313
Prognostic Factors 315
Complications of Surgery 317
The Learning Curve of Cytoreduction with HIPEC 318
Conclusion 320
References 320
HIPEC with Oxaliplatin in the Treatment of Peritoneal Carcinomatosis of Colorectal Origin 323
Introduction 323
Patient Eligibility and Surgical Procedures 324
Hyperthermic Intraperitoneal Chemotherapy (HIPEC) 324
Results of a Phase I Study of HIPEC with Oxaliplatin 325
Results of a Phase I Study with Oxaliplatin using Hypotonic Solutions 326
Results of a Phase II Study of HIPEC with Oxaliplatin 327
Comparison of HIPEC with Oxaliplatin versus Standard Systemic Chemotherapy 330
Phase I study of HIPEC combining Oxaliplatin and Irinotecan 333
Relation between the Extent of Cytoreductive surgery and the Rate of Postoperative Hematological Toxicity 334
Future Directions and Conclusion 335
Aknowledgement 336
References 336
Clinical Results of Cytoreduction and HIPEC in Pseudomyxoma Peritonei 339
Introduction 339
Site of Origin of PMP 339
Pathological Classification of Appendiceal Neoplasms 340
Clinical Trials of Cytoreduction and Intraperitoneal Chemotherapy 341
Conclusion 344
References 345
The Impact of Therapy in the Treatment of Pseudomyxoma Peritonei 349
Introduction 349
Memorial Sloan-Kettering Cancer Center Experience 351
Methods 352
Clinicopathologic Features 353
Operative Results 353
Long term overall survival 355
Evaluating the Impact of Therapy for PMP 356
References 360
Clinical Results of Cytoreduction and HIPEC for Malignant Peritoneal Mesothelioma 363
Introduction 363
Results of Cytoreduction and HIPEC 365
Summary 372
References 373
Cytoreduction and Intraperitoneal Chemotherapy for Carcinomatosis from Gastric Cancer 376
Introduction 376
Diagnosis of Peritoneal Carcinomatosis 376
Results of Systemic Chemotherapy in the Treatment of PC of Gastric Origin 379
Treatment of PC of Gastric Origin with Intraperitoneal Chemotherapy 381
Perioperative Intraperitoneal Chemotherapy 382
Conclusion 388
References 388
Cytoreduction and Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Ovarian Cancer 393
Introduction 393
Cytoreductive Surgery 394
Hyperthermic Intraperitoneal Chemotherapy 396
Refractory Ovarian Cancer 399
Prognostic Factors Affecting Patient Survival 399
Conclusion 400
References 400
The role of Neoadjuvant Chemotherapy versus Primary Surgery in the Management of Stage III Ovarian Cancer 404
Introduction 404
Primary Cytoreductive Surgery 405
Neoadjuvant Chemotherapy and Interval Cytoreduction 409
Laparoscopy to select Patients for Neoadjuvant Chemotherapy 413
References 414
Morbidity and Quality of Life following Cytoreduction and HIPEC 420
Introduction 420
Morbidity and Mortality following Cytoreduction and HIPEC 420
Milano National Cancer Institute Experience 423
Bowel Complications following Cytoreduction and HIPEC 427
Quality of Life following Cytoreduction and HIPEC 432
References 432
Detection and Treatment of Recurrent Disease after Cytoreduction and HIPEC 436
Follow-up after Cytoreduction 436
Treatment of Recurrent Disease 439
References 440
Systemic Chemotherapy in Patients with Peritoneal Carcinomatosis from Colorectal Cancer 442
Introduction 442
Peritoneal Carcinomatosis in Trials of Systemic Chemotherapy 442
Treatment strategy 452
References 452
Systemic Chemotherapy in patients with Peritoneal Carcinomatosis from Non Colorectal Origin 458
Introduction 458
Systemic Therapy 459
Conclusion 462
References 463
The Role of Radiotherapy in the treatment of Peritoneal Carcinomatosis 466
Introduction 466
PC Originating from Gastrointestinal Cancers 467
PC Originating from Gynaecological Cancers 468
PC Originating from Other Cancers 469
Conclusions and Future Prospects for Radiotherapy - the Role of Intensity Modulated Arc Therapy 470
References 472