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