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Multidisciplinary Management Of Gastrointestinal Cancers

BOOK

Multidisciplinary Management Of Gastrointestinal Cancers

Sun Weijing

(2016)

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Additional Information

Book Details

ISBN
978-981-4651-87-5
Edition
Language
English
Pages
625
Subjects
Oncology
Gastroenterology
Surgery

Abstract

This invaluable book provides an introduction to the development and application of molecular biology with a focus on translational research development in a variety of gastrointestinal cancers.Multidisciplinary Management of Gastrointestinal Cancers will emphasize the multidisciplinary aspects of GI cancer diagnosis, treatment and management, introduce the application of new techniques in GI cancer therapy; guide clinicians/experts to use newly developed evidence-based information and knowledge in patient care.This book with also discuss the role of supportive care and quality of life issues in patients with GI malignancies.

Table of Contents

Section Title Page Action Price
Contents v
Preface ix
List of Contributors xi
Chapter 1 The Role of Hereditary and Environmental Factors in Gastrointestinal Cancers 1
1 Introduction 1
2 Colon Cancer 2
2.1 Non-genetic risk factors 2
2.2 Genetic risk factors 2
2.2.1 Lynch syndrome 2
2.2.2 Familial adenomatous polyposis (FAP) 6
2.2.3 Attenuated familial adenomatous polyposis (AFAP) 6
2.2.4 MUTYH-associated neoplasia (MAN) 7
2.2.5 Juvenile polyposis syndrome (JPS) 7
2.2.6 Peutz–Jeghers syndrome (PJS) 8
2.2.7 Cowden syndrome 9
2.2.8 Hereditary diffuse gastric cancer (HDGC) 9
2.2.9 Serrated polyposis syndrome (SPS) 9
2.2.10 Other genes 10
3 Esophageal Cancer 10
3.1 Adenocarcinoma 11
3.2 Squamous cell carcinoma 11
4 Gastric Cancer 12
4.1 Non-genetic risk factors 12
4.1.1 Medical 12
4.1.2 Lifestyle 13
4.2 Genetic risk factors 13
5 Pancreatic Cancer 14
5.1 Non-genetic risk factors 14
5.2 Genetic risk factors 14
6 Cholangiocarcinoma 16
6.1 Non-genetic risk factors 16
6.2 Genetic risk factors 17
7 Gallbladder Cancer 17
8 Small Intestine Cancers 18
References 18
Chapter 2 Immunotherapy in Gastrointestinal Malignancies 27
1 Introduction 27
2 Colorectal Cancer Immunotherapy 31
2.1 The immune response to colorectal cancer 31
2.2 Immune therapies for CRC 33
2.2.1 Non-specific immune activation 33
2.2.2 Cancer vaccines for CRC 33
2.2.3 Adoptive transfer of T cells, CAR-T cells, BiTE and antibodies mediating ADCC 43
2.2.4 Checkpoint blockade 43
3 Pancreatic Cancer Immunotherapy 44
3.1 The immune response to pancreatic cancer 44
3.2 Tumor antigens in pancreatic cancer 44
3.3 Vaccines for pancreatic cancer 44
3.4 Adoptive immunotherapy for pancreatic cancer 47
3.5 Checkpoint blockade 47
4 Hepatocellular Carcinoma Immunotherapy 48
4.1 The immune response to hepatocellular carcinoma 48
4.2 Tumor antigens 49
4.3 Review of immune therapies for hepatocellular carcinoma 49
5 Immunotherapy for Biliary Cancers 50
5.1 The immune response to biliary malignancies 50
5.2 Tumor antigens 51
5.3 Immunotherapy for biliary malignancies 51
6 Immunotherapy for Gastroesophageal Malignancies 52
6.1 The immune response to esophagogastric cancers and targeted tumor antigens 52
6.2 Immunotherapy strategies for gastroesophageal cancer 53
6.3 Most recent development: PD-1 blockade in the treatment of gastric cancer 54
7 Anal Cancer 55
7.1 Role of immune cell infiltrate and tumor antigens 55
7.2 Immunotherapeutic strategies for anal cancer 55
8 Conclusions 56
9 Addendum: PD-1 Blockade in the Treatment of MSI High Malignancies Including Colon Cancer 56
References 57
Chapter 3 The Role of EMR and Ablative Therapies for Barrett’s Mucosa and Early Esophageal Cancer 71
1 Introduction 71
2 Ablative Therapies for Barrett’s Esophagus 72
2.1 Argon plasma coagulation 72
2.2 Photodynamic therapy 73
2.3 Radiofrequency ablation 74
2.4 Cryotherapy 76
2.5 Acid reduction 77
2.6 Post-ablation surveillance 77
3 Endoscopic Treatment of Early Esophageal Cancer 77
3.1 Endoscopic mucosal resection techniques 78
3.2 Endoscopic mucosal resection for cure 80
4 Conclusion 83
References 83
Chapter 4 The Role of Peri-Operative Therapy in Esophageal and Gastric Cancers 87
1 Esophageal Cancer 87
1.1 Introduction 87
1.2 Epidemiology 87
1.3 Presentation and staging 88
1.4 Approaches to therapy 88
1.4.1 Unresectable 89
1.4.2 Cervical esophagus 89
1.4.3 Resectable 89
1.5 Pre-operative chemotherapy 89
1.6 Peri-operative chemotherapy 90
1.7 Pre-operative concurrent chemoradiotherapy 90
1.8 Adjuvant therapy 91
1.8.1 Chemoradiotherapy 91
1.8.2 Chemotherapy 92
1.9 Summary 92
2 Gastric Cancer 93
2.1 Introduction 93
2.2 Epidemiology 93
2.3 Presentation and staging 94
2.3.1 Presenting symptoms 94
2.3.2 Endoscopy 94
2.3.3 Pathology 95
2.3.4 Staging 95
2.4 Approaches to management 95
2.4.1 Surgical resection 95
2.4.1.1 Importance of nodal dissection 96
2.4.2 Peri-operative chemotherapy 97
2.4.3 Surgery followed by adjuvant therapy 98
2.5 Conclusions 100
3 Unanswered Questions and Ongoing Studies 100
References 102
Chapter 5 Surgical Treatment of Esophagogastric Junction Tumors 107
1 Introduction 107
2 Staging 107
3 Tumor Classification 108
3.1 TNM classification 108
4 Principles of Surgical Resection 109
4.1 Types of resection 110
4.2 Resection margins 111
4.2.1 Proximal (esophageal) resection margin 111
4.2.2 Distal (gastric) resection margin 111
4.3 Lymph node involvement 112
4.4 Optimal lymphadenectomy 113
4.5 Extent of lymphadenectomy 115
5 Surgical Approaches 116
5.1 Ivor Lewis esophagectomy 116
5.2 McKeown (three-incision) esophagectomy 116
5.3 Left thoracoabdominal esophagectomy 117
5.4 Transhiatal esophagectomy 117
5.5 Transhiatal extended total gastrectomy 117
5.6 Minimally invasive esophagectomy 118
5.6.1 Surgical procedure for Ivor Lewis MIE 118
6 Oncologic Outcomes After Surgical Treatment 120
6.1 Survival 120
6.2 Recurrence 121
7 Comparative Studies of Surgical Approaches 123
7.1 Transhiatal versus transthoracic esophagectomy 123
7.2 Minimally invasive versus open esophagectomies 124
8 Conclusions 125
References 125
Chapter 6 Gastric Cancer Management: East vs. West? 133
1 Introduction 133
2 Differences in Epidemiology Between the East and the West 133
3 Localized Gastric Cancer 134
3.1 Differences in surgical approach 134
3.2 Differences in surgical outcomes and recurrence patterns 136
3.3 Differences in perioperative therapies 137
3.3.1 Postoperative adjuvant chemoradiation 137
3.3.2 Perioperative therapy including neoadjuvant chemotherapy 138
3.3.3 Postoperative adjuvant chemotherapy 138
3.3.4 Different strategies to improve perioperative therapy 139
4 Unresectable or Metastatic Gastric Cancer 141
4.1 First-line cytotoxic chemotherapy 141
4.2 Second-line or further cytotoxic chemotherapy 144
4.3 Molecular-targeted agents 145
5 Conclusions 147
References 148
Chapter 7 The Development of Systemic Therapies for Esophageal and Gastric Cancers 153
1 Introduction 153
2 Risk Factors 153
3 Genetics of Esophageal and Gastric Cancer 154
4 Cytotoxic Chemotherapy 154
4.1 Treatment of gastric cancer by subtype 155
5 Targeted Therapy 156
5.1 ErbB receptor family 156
5.2 HGF–MET 159
5.3 Vascular endothelial growth factor 160
5.4 JAK/STAT 161
5.5 Notch signaling 162
5.6 Immune checkpoints 162
6 Summary 164
References 164
Chapter 8 Intraperitoneal Therapy of Gastrointestinal Cancers 171
1 Background/Introduction 171
2 Anatomy/Pathophysiology 171
3 Appendiceal Neoplasms 173
3.1 Pseudomyxoma peritonei 173
3.2 Clinical presentation and diagnosis 173
3.3 Therapy 176
3.4 Follow-up/surveillance 178
4 Colorectal Carcinoma 180
4.1 Clinical presentation and diagnosis 180
4.2 Therapy 182
4.3 Follow-up/surveillance 183
5 Gastric Carcinoma 184
6 Conclusions 185
References 186
Chapter 9 The Role of Diagnostic Radiology in Pancreatic Cancer Management 189
1 Introduction 189
2 Clinical Findings 190
3 Multimodality Imaging and Diagnosis 190
4 Staging 201
5 Surveillance 207
6 Differential Diagnosis 207
7 Conclusion 210
References 210
Chapter 10 Radiotherapy for Pancreatic Cancer 215
1 Introduction 215
2 Rationale for Adjuvant Therapy for Resectable or Borderline Resectable Disease 215
3 Resectable Patients 216
3.1 Retrospective series of adjuvant radiation therapy after resection 216
3.2 Randomized clinical trials utilizing adjuvant radiation therapy following resection 217
4 Borderline Resectable Patients 221
4.1 Neoadjuvant chemoradiation for borderline resectable or resectable patients 221
5 Unresectable Disease 223
5.1 Upfront chemoradiation therapy for unresectable disease 223
5.2 Chemoradiation after induction chemotherapy for unresectable disease 224
6 Metastatic Pancreatic Cancer 226
7 Radiation Treatment Planning and Techniques 226
8 Radiation Therapy Treatment Modalities 227
9 Conclusions 228
References 229
Chapter 11 Advances in the Surgical Approach to Pancreatic Cancer 233
1 Introduction 233
2 Evolution of Pancreatic Cancer Surgery 233
3 Evolution of Minimally Invasive Pancreas Surgery 234
4 Robotic Surgery 234
4.1 Robotic pancreaticoduodenectomy 235
4.2 Robotic distal pancreatectomy 237
4.3 Robotic central pancreatectomy 240
4.4 Other robotic-assisted pancreatic procedures 241
4.5 Benefits of the robotic platform 241
4.6 Limitations of the robotic platform 243
5 Conclusions 243
References 244
Chapter 12 Systemic Therapy in Pancreatic Cancer 247
1 Introduction 247
2 Pathology 248
3 Etiology 248
4 Genomics of Pancreatic Cancer 250
5 Clinical Presentation 251
6 Diagnostic Work-Up 251
6.1 Tumor markers 252
7 Clinical Staging of Pancreatic Cancer 252
8 Systemic Therapy 253
8.1 Systemic therapy for resectable disease (adjuvant therapy) 253
8.2 Systemic therapy for borderline resectable disease 256
8.3 Systemic therapy for locally advanced disease 257
8.4 Systemic therapy for metastatic disease 259
9 Future Directions in Systemic Therapy 263
10 Conclusions 265
References 266
Chapter 13 Systemic Therapy for Metastatic Colorectal Cancer 275
1 Introduction 275
2 Cytotoxic Chemotherapy 276
2.1 Antimetabolites 276
2.1.1 5-fluorouracil 276
2.1.2 Capecitabine 278
2.1.3 Dihydropyrimidine dehydrogenase 281
2.2 Topoisomerase inhibitors 282
2.2.1 Irinotecan 282
2.2.2 UGT1A1 286
2.3 Alkylating agents 286
2.3.1 Oxaliplatin 286
2.4 Oxaliplatin versus irinotecan 292
2.5 Oxaliplatin and irinotecan combinations 293
3 Biologic Therapies 294
3.1 VEGF inhibitors 294
3.1.1 Bevacizumab 294
3.1.1.1 Bevacizumab after progression 300
3.1.2 Aflibercept 300
3.1.3 Ramucirumab 301
3.1.4 Regorefenib 302
3.2 EGFR inhibitors 302
3.2.1 EGFR pathway mutations 303
3.2.1.1 RAS mutations 303
3.2.1.2 BRAF mutations 310
3.2.2 Cetuximab 311
3.2.3 Panitumumab 313
3.3 Biologic combinations 314
3.4 Comparisons of biologic therapies 314
4 Maintenance Therapy and Duration of Therapy 315
4.1 Chemotherapy breaks 316
4.2 Maintenance therapy 316
5 Emerging Treatments: Immunotherapy 318
6 Conclusions 319
References 320
Chapter 14 Local and Locally Advanced Rectal Cancer 339
1 Introduction 339
2 Local and Regional Staging 340
2.1 Physical exam 340
2.2 Imaging 340
2.2.1. Endorectal ultrasound 340
2.2.2 Magnetic resonance imaging 341
2.2.3 Distant metastases 342
3 Surgical Therapy 343
3.1 Local excision 343
3.2 Radical excision 344
3.2.1 Sphincter-sparing surgery 345
3.2.2 Abdominoperineal resection 345
3.2.3 Total mesorectal excision 345
4 Adjuvant and Neuoadjuvant Therapy 346
4.1 Adjuvant therapy 346
4.1.1 Postoperative chemoradiotherapy and continuous infusion fluorouracil 346
4.2 Preoperative vs. postoperative chemoradiotherapy 348
4.3 Short-course radiotherapy vs. long-course chemoradiotherapy in the preoperative setting 349
4.4 Is chemotherapy after preoperative CRT and surgery necessary? 350
4.5 Neoadjuvant chemoradiotherapy: Roles of capecitabine and oxaliplatin during radiotherapy 351
4.6 Role of oxaliplatin in postoperative chemotherapy 352
4.7 Can some patients be spared radiotherapy? 353
4.8 Induction chemotherapy followed by chemoradiation? 354
5 Role of Biologic Agents in Rectal Cancer 355
6 Summary and Authors’ Recommendations by Clinical Stage\r 355
Recommended therapy by stage 356
References 356
Chapter 15 Adjuvant Chemotherapy of Colon Cancer: Histology vs. Biology 363
1 Introduction 363
2 The Role of Fluoropyrimidines 364
3 Role of Oxaliplatin in Adjuvant Chemotherapy 365
4 The Role of Irinotecan in Adjuvant Chemotherapy 370
5 The Role of Biologics in Adjuvant Therapy 371
6 Stage II Colon Cancer 373
7 Treatment Considerations in the Elderly 374
8 Optimal Duration of Adjuvant Chemotherapy 375
9 Risk Stratification Based on High-Risk Prognostic Features and Predictive Molecular Biomarkers 376
9.1 High-risk prognostic features in stage II disease 376
9.2 Predictive molecular biomarkers for adjuvant therapy 377
9.3 Gene expression signatures 379
10 Pharmacoeconomic Considerations in Adjuvant Chemotherapy 380
11 On-Going Phase III Adjuvant Studies 381
11.1 QUASAR-2 adjuvant trial 381
11.2 CALGB/SWOG colon trial C80702 (CLEAR Colon Trial); a phase III trial of 6 vs. 12 treatments of adjuvant FOLFOX plus celecoxib or placebo for patients with resected stage III colon cancer 382
12 Future Directions 382
13 Conclusion 383
References 384
Chapter 16 Hepatocellular Carcinoma: Liver Transplantation, Hepatic Resection, and Regional Treatment Options 391
1 Introduction 391
2 Surgical Resection or Liver Transplantation for Early HCC 392
2.1 Liver transplantation 392
2.2 Liver resection (LR) 396
2.3 Role of minimally invasive surgery 397
2.4 Liver resection versus liver transplantation decision making 398
3 Tumor Biology 402
4 Local Therapy 403
5 Regional Therapy 407
6 Systemic Therapy 409
6.1 Systemic therapy for advanced/metastatic disease 409
6.2 Adjuvant therapy 411
7 Conclusions 411
References 412
Chapter 17 Cholangiocarcinoma and Gallbladder Cancer 423
1 Introduction 423
2 Anatomy and Classification\r 423
2.1 Hilar classification 424
2.2 Epidemiology 425
2.2.1 Risk factors for cholangiocarcinoma 426
2.2.2 Risk factors for gallbladder cancer 428
2.3 Pathology 428
2.3.1 Molecular pathogenesis 430
3 Diagnosis 431
3.1 Clinical presentation 431
3.2 Laboratory studies 432
3.3 Radiographic studies 432
4 Staging 435
5 Surgical Resection 438
5.1 Intrahepatic cholangiocarcinoma 439
5.2 Distal cholangiocarcinoma 439
5.3 Hilar cholangiocarcinoma 440
5.4 Gallbladder cancer 440
5.5 Adjunct operative procedures 441
5.6 Adjuvant therapy 441
5.7 Liver transplantation 443
5.8 Locoregional therapy 444
5.8.1 Radiation therapy 444
5.8.2 Transarterial chemoembolization 444
5.8.3 Radiofrequency ablation 446
5.8.4 Photodynamic therapy 446
6 Systemic Chemotherapy 447
7 Future Directions 452
References 452
Chapter 18 Neuroendocrine Tumors 473
1 Introduction 473
2 Epidemiology 474
3 The Cell of Origin 475
4 Tumor Biology 476
5 Pathology, Staging, and Prognosis 477
6 Clinical Features 478
7 Familial Neuroendocrine Syndromes 479
8 Sporadic GEP-NETs 480
8.1 Small bowel NETs 480
8.2 Gastric NETs 480
8.3 Appendiceal and colorectal carcinoids 480
8.4 Pancreatic NETs 481
9 Diagnosis 482
10 Follow-Up 483
11 Surgical Approach to GEP-NETs 484
12 Systemic Treatment of Metastatic GEP-NETs 485
12.1 Somatostatin analogs and peptide–receptor radiotherapy 485
12.2 Interferon-α 487
12.3 mTOR inhibitors 488
12.4 Angiogenesis inhibitors 489
12.5 Cytotoxic chemotherapy 490
13 Management of Liver Metastases 491
14 Conclusions 492
References 493
Chapter 19 Management of Gastrointestinal Stromal Tumors 503
1 Introduction 503
2 Clinical Presentation and Diagnosis: 504
2.1 Clinical presentation 504
2.2 Diagnosis 504
2.3 Staging and risk stratification 506
3 Treatment 508
3.1 Surgical approach and principles 508
3.2 Adjuvant therapy 508
3.3 Neoadjuvant therapy 509
3.4 Recurrent and metastatic disease 510
4 Resistance to Imatinib Treatment 512
4.1 Continue treatment vs. dose escalation 512
4.2 Other tyrosine kinase inhibitors 513
4.2.1 Sunitinib 513
4.2.2 Regorafenib 513
4.2.3. Nilotinib 514
5 Conclusions 514
References 514
Chapter 20 Small Intestinal Cancers 519
1 Introduction 519
2 Epidemiology 519
2.1 Etiopathogenesis 520
2.1.1 Lifestyle 520
2.1.2 Crohn’s disease 521
2.1.3 Celiac disease 521
2.1.4 Genetic predisposition 521
2.1.4.1 Familial adenomatous polyposis 521
2.1.4.2 Hereditary non-polyposis colorectal cancer 521
2.1.4.3 Peutz–Jeghers syndrome 522
2.1.4.4 Other genetic syndromes 522
3 Clinical Presentation 522
4 Diagnosis 522
5 Adenocarcinoma 524
5.1 Genetics 525
5.2 Staging/prognosis 525
5.3 Management 526
5.3.1 Localized disease 526
5.3.2 Adjuvant therapy 527
5.3.3 Palliative chemotherapy 527
6 Carcinoid Tumors 529
6.1 Staging/prognosis 529
6.2 Management 530
6.2.1 Localized disease 530
6.2.2 Advanced disease 530
6.2.3 Systemic therapy 531
6.2.4 Peptide receptor radionuclide therapy 532
7 Sarcomas 532
7.1 Genetics 533
7.2 Prognosis 533
7.3 Management 534
7.3.1 Limited disease 534
7.3.2 Advanced disease 534
8 Intestinal Lymphomas 536
8.1 Histologic type/staging/prognosis 536
8.2 Specific primary lymphoma subtypes and management 539
8.2.1 Diffuse large B-cell lymphoma 539
8.2.2 Follicular lymphoma 539
8.2.3 Burkitt lymphoma 540
8.2.4 Marginal zone B-cell lymphoma 540
8.2.5 Mantle-cell lymphoma 540
8.2.6 Enteropathy-associated T-cell intestinal lymphoma 541
References 541
Chapter 21 Importance of Supportive and Palliative Care in Gastrointestinal Malignancies 555
1 Introduction 555
2 General Complications of Gastrointestinal Cancers 555
2.1 Psychosocial distress 555
2.2 Fatigue 556
2.3 Anorexia/cachexia 557
2.4 Early satiety 559
2.5 Role of nutrition support in gastrointestinal cancers 559
2.5.1 Enteral versus parenteral nutrition 560
2.5.1.1 Enteral nutrition 560
2.5.1.2 Parenteral nutrition 561
2.6 Pain 561
2.7 Nausea/vomiting 563
3 Metastatic Complications of Gastrointestinal Malignancies 567
3.1 Malignant bowel obstruction 567
3.2 Malignant ascites 569
3.3 Pruritus 2/2 malignant obstructive jaundice 570
4. Treatment Related Complications of Gastrointestinal Malignancies 572
4.1 Changes in taste and smell 572
4.2 Chemotherapy-induced nausea/vomiting 573
4.3 Chemotherapy-induced neuropathy 573
4.4 Chemotherapy-associated diarrhea 575
4.5 Chemotherapy-associated alopecia 575
4.6 Rash secondary to epidermal growth factor receptor (EGFR) inhibitors 576
5 Supportive Care by Cancer Site 577
5.1 Esophageal cancer complications 577
5.1.1 Malignant dysphagia 577
5.1.2 Radiation complications 578
5.1.3 Nutritional concerns in esophageal cancer 578
5.1.3.1 Changes in eating patterns 578
5.1.3.2 Dumping syndrome 579
5.2 Gastric Cancer Complications 580
5.2.1 Nutrition concerns in gastric cancer 580
5.2.1.1 Nutrition after Gastric resection 580
5.2.1.2 Dumping syndrome 580
5.2.1.3 Fat maldigestion 580
5.2.1.4 Gastric stasis 581
5.2.1.5 Lactose intolerance 581
5.2.2 Nutrition related anemia 581
5.2.3 Osteoporosis risk 582
5.3 Colorectal Cancer Complications 583
5.3.1 Sacral pain management 583
5.3.2 Pelvic bleeding 583
5.3.3 Low anterior resection (LAR) syndrome 583
5.3.4 Nutrition concerns in colorectal cancers 584
5.4 Pancreatic and Bile Duct Cancer Complications 584
5.4.1 Nutrition concerns in pancreatic and bile duct cancers 584
5.4.1.1 Pancreatic exocrine insufficiency and malabsorption 584
5.4.1.2 Potential micronutrient deficiencies 586
5.4.2 Diabetes and glucose intolerance 586
5.4.3 Nutrition intolerances after pancreatic resection 587
References 587
Index 597

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