Pancreatic Cancer: A Multidisciplinary Approach: A Multidisciplinary Approach

Foreword: The Evolution of Pancreatic Cancer Care
Preface
Contents
Contributors
1: Pancreatic Cancer at a Glance
Introduction
Incidence
Prevalence
Mortality
Human Development Index
Incidence Projections
Mortality Projections
Conclusion
References
2: Risk Factors and Genetic Predisposition
Smoking
Obesity
Alcohol
Chronic Pancreatitis
Family History
Genetic Predisposition
References
3: Pancreatic Cancer and Diabetes Mellitus
Background
Multidirectional Interaction Between DM and PDAC (Fig. 3.1)
Pathogenesis of Glycemic Disturbance due to PDAC
New-Onset Diabetes as a Harbinger of PDAC
Efforts to Use NOD for Early Detection of PDAC
Summary
References
4: Pancreatic Cancer Screening
Introduction
Pancreatic Cancer Risk Factors
Pancreatic Cancer Precursor Lesions
Who Should Be Screened?
Screening Tests
Screening Guidelines and Strategies
MD ANDERSON Screening Algorithm
Benefits and Harms
Psychological Impact of Pancreatic Cancer Screening
Future Directions
Conclusions
References
Part I: Diagnosis and Staging of Pancreatic Cancer
5: Diagnosis and Staging of Pancreatic Cancer: Imaging Evaluations—Pancreatic Protocol CT and MRI, PET-CT
Computed Tomography
CT Protocol
Diagnosis
Differential Diagnosis
Staging
Positron Emission Tomography/Computed Tomography
PET/CT Protocol
Diagnosis
Staging
Treatment Response
Detection of Recurrent Disease
Magnetic Resonance Imaging
MRI Protocol
Diagnosis
Staging
Assessment of Recurrent Cancer
Conclusion
References
6: Diagnosis and Staging of Pancreatic Cancer: Laparoscopy
Introduction
History
Review of Contemporary Data
Diagnostic Accuracy and Outcomes
Cost-Effectiveness
Principles of Management
Indications
Preoperative Setting
Staging Clarification Prior to Upfront Surgical Resection or Neoadjuvant Therapy
Staging Clarification During Neoadjuvant Therapy
Risk Stratification Prior to Surgery
Intraoperative Setting
Staging Clarification Immediately before Laparotomy
Postoperative Setting
Staging Clarification for Adjuvant Therapy
Biospecimen Acquisition
Technical Points
Drawbacks
Conclusion
References
7: Diagnosis and Staging of Pancreatic Cancer: Role of Gastroenterologist: Endoscopic Ultrasound (EUS), EUS-Guided Biopsy
Introduction
Detection and Diagnosis
Staging
Management
Adjuvant Molecular Testing
Conclusion
References
8: Diagnosis and Staging of Pancreatic Cancer: Role of Ca 19-9 in Diagnosis/Staging and Management
References
Part II: Management of Locally Advanced/Metastatic Disease
9: Management of Locally Advanced/Metastatic Disease: Medical Oncology
Introduction
Locally Advanced Disease
Metastatic Disease
Approach to LAPC at MD Anderson
MD Anderson Approach to Metastatic Pancreatic Cancer
Conclusion
References
10: Management of Locally Advanced/Metastatic Disease: Radiation Oncology
Introduction
Radiation Therapy Treatment Strategies for Unresectable Disease
Chemoradiation
Proton and Carbon Ion Therapy
Stereotactic Body Radiation Therapy (SBRT)
Magnetic Resonance Linac-Based Treatment
Treatment Planning Procedures
Pre-simulation Instructions
Patient Set-Up
Image Acquisition
Treatment Planning
Planning Aims and Dose Constraints
Treatment Verification
Summary
References
Part III: Management of Resectable and Borderline Resectable Disease
11: Management of Resectable and Borderline Resectable Disease: Surgery
Introduction
History of Pancreatoduodenectomy
Preoperative Management
Preoperative Period: Opportunity for Optimization
Decision for Surgery
Operative Steps
Pancreatoduodenectomy
Considerations for Vein Involvement
Reconstruction
Distal Pancreatectomy
Postoperative Management
Enhanced Recovery
Quality Measures
Future Directions
References
12: Management of Resectable and Borderline Resectable Disease: Medical Oncology
Introduction
Definition of Resectability
Adjuvant Therapy
Borderline Resectable PDAC
Neoadjuvant Therapy for PDAC
Role of Neoadjuvant Chemotherapy without Radiation
Locally Advanced PDAC
What Is the Role of Radiotherapy in the Neoadjuvant Setting for PDAC?
Histopathologic Assessment Following Neoadjuvant Therapy
Tumor Surveillance in PDAC Using Circulating DNA (ctDNA)
Neoadjuvant Therapy Followed by Metastasectomy for PDAC
References
13: Management of Resectable and Borderline Resectable Disease: Radiation Oncology
Introduction
Indications for Radiation
Adjuvant Radiation
Neoadjuvant Radiation
Definitive Radiation
The Impact of Advanced Technologies in Radiation Delivery
Imaging and Target Delineation
Internal Motion Management
Image-Guided Radiation Therapy
MR-Linac
Innovations in Radiation Techniques
Intensity-Modulated Radiation Therapy
SBRT
Particle Beam Radiation
Conclusions
References
Part IV: Endoscopic Management of Pancreatic Cancer Symptoms
14: Jaundice/Biliary Obstruction: ERCP/EUS BD
Introduction
Options for Biliary Decompression
References
15: Gastric Outlet Obstruction: Antroduodenal Stenting, Venting PEG, EUS Guided Gastrojejunostomy
Introduction
Pathophysiology
Diagnosis
Principles of Management
Surgical Gastrojejunostomy
Enteral Stent Placement
Technique
Outcomes and Efficacy
Adverse Events
Enteral Stents Versus Surgical Gastrojejunostomy
EUS-Guided Gastroenterostomy
Technique
Outcomes and Efficacy
EUS-GE Versus Surgical Gastrojejunostomy
EUS-GE Versus Enteral Stents
Adverse Events
Venting Gastrostomy
Special Considerations
mGOO in the Post-Whipple Anatomy
Delayed Gastric Emptying
Summary and Management Algorithm
References
16: Pain Control: Celiac Plexus Neurolysis
Percutaneous Celiac Plexus Neurolysis
Method
Anterior Approach
Posterior Approach
Complications
Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis
Method
Instruments
Drugs
Procedure
Bilateral Approach (Fig. 16.1)
Central Injection Approach (Fig. 16.2)
Complications
References
Part V: Emerging Paradigms in Pancreatic Cancer
17: Minimally Invasive Surgical Approaches
Introduction
Minimally Invasive DP
Minimally Invasive PD
Foregut Robotic Surgery Program at MD Anderson
Conclusion
References
18: EUS-Guided Local Therapies
Introduction
EUS-Guided Fine Needle Injection of Anti-Tumor Agents
EUS-Assisted Radiotherapy
EUS-Guided Brachytherapy
EUS-Guided Fiducial Placement
EUS-Guided Tumor Ablation
Conclusion
References
19: Imaging-Based Biomarkers for Pancreatic Cancer
Introduction: Different Contexts of Imaging for Pancreatic Cancer and How Imaging-Derived Biomarkers May Play a Role
Considerations for Early Detection
Prognostic Stratification of Tumors
Treatment Response
Specific Imaging Modalities
Endoscopic Ultrasound {EUS}
Computed Tomography (CT)
MRI
Artificial Intelligence
Future Applications
References
20: Liquid Biopsies in Pancreatic Cancer
Introduction
CTCs in Pancreatic Cancer
Circulating Free DNA (cfDNA) and Circulating Tumor DNA (ctDNA)
EVs
References
21: Molecular Profiling and Precision Medicine for Pancreatic Cancer
Introduction
Sequencing Efforts Have Revealed Actionable Mutations
Best Examples to Date
BRCA1/2 (and PALB2)
MSI-High
NTRK
Promising Targets
Other DDR Mutations
KRAS Wild Type PDAC: Mutations in BRAF, and Other Receptor Tyrosine Kinases
Targeting the WNT Pathway: RNF43 Mutations and RSPO2/3 Fusions
Survival Benefit—A National Registry for Precision Medicine (the Know Your Tumor Program)
Elusive Drivers
KRAS, TP53, CDKN2A/2B, and SMAD4
Immunotherapy
Future Directions: Other Considerations and Biomarker Driven Approaches
Concluding Remarks
References
22: The Prospects of Immunotherapy in Pancreatic Cancer
The Formation of Immune-Suppressive Microenvironment
Tumor Cell-Intrinsic Factors
Stroma Fibroblast
T Lymphocytes
Myeloid Cells
Metabolism Environment
Microbiome
The Current Status and Prospect of Immunotherapy
Immune Checkpoint Blockade
Tumor Vaccine
Adoptive Cell Therapy (ACT)
Targeting TME
Conclusion
References
23: Microbiome in Pancreatic Cancer
Introduction on Microbiome
Microbial Biomarkers in Pancreatic Cancer
Role of Pancreatic Microbiome in Preclinical Studies: Exploring Functional Relevance
Ongoing Clinical Trials for Targeting the Microbiome During Cancer
References
24: Early Drug Development in Pancreatic Cancer
Introduction
Targeting the Tumor Microenvironment
T-Cell Checkpoint Inhibitors
Other Immune Based Strategies
Targeting the Stroma
Targeting Tumor Cells
KRAS-Based Targets
Autophagy
Other Targets
Conclusions
References
25: Mechanisms and Evidence on Pancreatic Cancer Prevention
Introduction
Metformin
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Statins
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Aspirin
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Vitamin D
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Vitamin C
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Vitamin E
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Antibiotics
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Immune Checkpoint Inhibitors
General Background and PC Risk Association
Anti-tumoral and Immunomodulatory Mechanisms
Clinical Use and Potential for PC Prevention
Conclusions and Perspective
References
26: Nutrition in Pancreatic Cancer
Introduction
Malnutrition, Cachexia, and Sarcopenia
Cachexia
Sarcopenia
Nutrition Screening
Malnutrition, Cachexia, and Sarcopenia Interventions in Pancreatic Cancer
Nutrition Intervention
Nutrient Needs
Calorie Needs
Protein Needs
Micronutrient Needs
Common Nutrition Issues in PC
Diabetes Mellitus and Hyperglycemia
Gastric Outlet Obstruction and Small Bowel Obstruction
Delayed Gastric Emptying
Pancreatic Exocrine Insufficiency (PEI)
Management of PEI
Pancreatic Enzyme Replacement Therapy
PERT Optimization and Troubleshooting
Diet Modification for Malabsorption
Diarrhea
Absorptive Fiber
Other Considerations
Special Populations: Perioperative Nutrition, Nutrition at End of Life, Long-Term Survivors
Perioperative Nutrition
Preoperative Nutrition
Postoperative Nutrition
Energy Needs
Nutrition for Surgical Complications
Rapid GI Transit or Dumping Syndrome
Pancreatic Fistula
Chyle Leak
Nutrition Support
End of Life
Ascites
Long-Term Survivors
Summary
References
27: Prioritizing the Patient Experience: Early Integration of Supportive/Palliative Care in Pancreatic Cancer Management
Introduction
Early Integrated Palliative Care in Patients with Cancer
Toxicities and Healthcare-Related Quality of Life Outcomes of Systemic Therapy
Integration of Health Care Related Quality of Life Measures into Clinical Trials
Providing Holistic Care for Patients with Pancreatic Cancer
Underutilization of Palliative Care in Cancer Therapy and Barriers to Earlier Integration of Palliative Care
References
28: Patient Reported Outcomes and Quality of Life
Introduction
Definitions of Quality of Life
Potential QoL Tools That Can Be Optimally Implemented for Patients with PDAC
Associated Tools to Collect Patient Reported Outcomes
Challenges in Implementing QoL Measures Into Clinical Trials
Statistical Challenges and Opportunities Related to QoL Analyses
QoL Clinical Studies
QoL Studies in Resectable Disease and Prior to Surgery
QoL in Adjuvant Therapy Studies
Neoadjuvant and Definitive Therapy: Resectable, Borderline Resectable, and Locally Advanced Pancreatic Cancer
Metastatic Disease
Elderly and Poor Performance Status Patients
Future Directions
References
29: Integrative Medicine in Pancreatic Cancer
Introduction
Definitions
Utilization
Communication
The Evidence
Supplements
Mind-Body Practices
Massage
Acupuncture
Educational Resources
Integrative Oncology in Clinical Practice
Conclusion
References
Index