Hepato-Pancreato-Biliary Malignancies: Diagnosis and Treatment in the 21st Century

Preface
Contents
About the Editors
Contributors
Part I: Hepatic Malignancies
	1 Approach to the Patient with a Solid Liver Mass
		1 Introduction
		2 Hepatic Hemangioma
		3 Pathogenesis and Pathology
		4 Clinical Presentation
		5 Ultrasound
		6 Treatment
		7 Hepatocellular Adenoma
		8 Pathophysiology
		9 Pathology
		10 Clinical Features
		11 Imaging Findings
			11.1 Ultrasonography and Contrast-Enhanced Ultrasonography
		12 Computed Tomography
		13 Magnetic Resonance Imaging (MRI)
		14 Treatment
		15 Focal Nodular Hyperplasia (FNH)
			15.1 Epidemiology
		16 Pathogenesis
		17 Pathology
		18 Clinical Presentation and Diagnosis
		19 Treatment
		20 Nodular Regenerative Hyperplasia
		21 Pathophysiology and Pathology
		22 Clinical Presentation and Diagnosis
		References
	2 Diagnosis and Evaluation of Hepatocellular Carcinoma
		1 Introduction
		2 HCC Surveillance
			2.1 Target Populations
				2.1.1 Individuals with Cirrhosis
				2.1.2 Non-Cirrhotic Individuals
				2.1.3 Surveillance Methodology
				2.1.4 Surveillance Tools
		3 Diagnosis
			3.1 Diagnosis via Imaging
				3.1.1 LI-RADS
				3.1.2 Diagnostic Performance of CT and MRI
				3.1.3 Contrast Enhanced Ultrasound
			3.2 Pathological Diagnosis
		4 Staging HCC
			4.1 Evaluation of Disease Extension
			4.2 Staging Systems
				4.2.1 Barcelona Clinic Liver Cancer Staging Classification
			4.3 Patient Selection for Transplantation
				4.3.1 Milan Criteria
				4.3.2 UCSF Criteria
		5 Multidisciplinary Approach to Evaluation
		References
	3 Hepatocellular Carcinoma Pathology
		1 Introduction
		2 Molecular Biology of Hepatocellular Carcinoma
			2.1 Molecular Pathogenesis of Hepatocellular Carcinoma
			2.2 Cytogenetics
			2.3 Next Generation Sequencing
		3 Specimen Submission Considerations
		4 Gross Examination
			4.1 Hepatocellular Carcinoma - Gross Findings
			4.2 Incidental Hepatocellular Carcinoma (iHCC)
			4.3 Tissue Sampling for Microscopic Examination
		5 Hepatocellular Carcinoma - Microscopic Features
		6 Background Liver - Microscopic Features
		7 Cytology
		8 Ancillary Studies
			8.1 Histochemical Stains
			8.2 Immunohistochemistry
			8.3 Immunostains to Distinguish Hepatocellular Carcinoma from Other Hepatocellular Tumors and Tumor-Like Conditions
			8.4 Immunostains to Confirm Hepatocellular Differentiation (and Distinguish HCC from Other Malignant Neoplasms)
		9 Precursor/Premalignant Lesions
			9.1 Dysplastic Nodule
			9.2 Hepatocellular Adenoma, β-Catenin Mutated
			9.3 Hepatocellular Neoplasm with Uncertain Malignant Potential (HUMP)/Hepatocellular Neoplasm with Atypical Characteristics (H...
		10 Subtypes of Hepatocellular Carcinoma
			10.1 Steatohepatitic Hepatocellular Carcinoma
			10.2 Clear Cell Hepatocellular Carcinoma
			10.3 Macrotrabecular Massive Hepatocellular Carcinoma
			10.4 Scirrhous Hepatocellular Carcinoma
			10.5 Sarcomatoid Hepatocellular Carcinoma
			10.6 Chromophobe Hepatocellular Carcinoma
			10.7 Neutrophil-Rich Hepatocellular Carcinoma
			10.8 Lymphocyte-Rich Hepatocellular Carcinoma
			10.9 Fibrolamellar Carcinoma
			10.10 Combined Hepatocellular Carcinoma - Cholangiocarcinoma
		11 Differential Diagnosis for Hepatocellular Carcinoma
			11.1 Other Hepatocellular Tumors (and Nontumors)
				11.1.1 Focal Fatty Change
				11.1.2 Macroregenerative and Dysplastic Nodules
				11.1.3 Focal Nodular Hyperplasia (FNH)
				11.1.4 Hepatocellular Adenoma (HCA)
				11.1.5 Fibrolamellar Carcinoma Versus Scirrhous Hepatocellular Carcinoma
				11.1.6 Scirrhous HCC Versus Cholangiocarcinoma
				11.1.7 Metastatic Cancer
			11.2 Clear Cell Tumors
			11.3 Nonhepatobiliary Neoplasms
				11.3.1 Angiomyolipoma
				11.3.2 Granular Cell Tumor
				11.3.3 Paraganglioma
				11.3.4 Angiosarcoma
				11.3.5 Epithelioid Hemangioendothelioma
		12 Microscopic Features After Local and Regional Therapy
			12.1 Radiofrequency Ablation
			12.2 Transarterial Chemoembolization
			12.3 Yttrium-90 (90Y, Y-90) Transarterial Radioembolization
		13 Tumor Grading and Staging
			13.1 Tumor Grading
				13.1.1 Edmondson-Steiner (ES) Classification
				13.1.2 Modified Edmondson-Steiner Classification
				13.1.3 Proposed 2019 W.H.O. Grading System
			13.2 Tumor Staging
				13.2.1 Milan Criteria
				13.2.2 TNM Classification
				13.2.3 Other Staging Systems
			13.3 Molecular Classification of Hepatocellular Carcinoma with Clinicopathological and Etiologic Correlates
		14 Beyond Diagnosis: Prognostic Factors
			14.1 Tumor Biomarkers
		15 Conclusion
		References
4 Metabolic Syndrome and Liver Cancer
	1 Introduction
	2 NAFLD Overview
		2.1 Epidemiology
		2.2 Pathophysiology
	3 Obesity
		3.1 Epidemiology
		3.2 Pathophysiology: Obesity in NASH and HCC
		3.3 Cytokine/Adipokine Alterations in Obesity
	4 Gender Disparities
	5 Diabetes
		5.1 Pathophysiology
		5.2 Diabetes and Hepatocarcinogenesis
	6 Receptor for Advanced Glycation End Products
		6.1 Diabetic Medications and HCC Risk
			6.1.1 Microbiome
			6.1.2 Ethnic and Genetic Risk Factors
	7 Conclusions
	References
5 Reducing the Risk of and Screening for Liver Cancer
	1 Introduction and Epidemiology
	2 Hepatitis B Virus, HBV
	3 Hepatitis C Virus, HCV
	4 Nonalcoholic Fatty Liver Disease, NAFLD
	5 Alcoholic Liver Disease, ALD
	6 Other Risk Factors
	7 Defining Prevention
	8 Hepatitis B Prevention
	9 Surveillance and Screening Goals
	10 Who Should Be Screened?
	11 In Whom Is Screening of Uncertain Benefit?
	12 Who Should Not Be Screened?
	13 Screening Modalities
		13.1 Imaging
		13.2 Biomarkers
		13.3 Screening Intervals
		13.4 Screening Algorithm
	14 Limitations of Surveillance
	15 Conclusion
	References
6 Medical Management of Hepatocellular Carcinoma
	1 Introduction
	2 Locoregional Therapy
		2.1 Ablation
		2.2 Arterial Directed Therapy
		2.3 Radiation Therapy
	3 Systemic Therapy
	4 Conclusion
	References
7 Surgical Management of Hepatocellular Carcinoma
	1 Introduction
	2 Clinical Setting and Risk Factors
	3 Diagnostic Tools and Oncologic Staging
	4 Surgical Treatments
		4.1 Liver Resection
		4.2 Liver Transplantation
		4.3 Hepatic Thermal Ablation
	5 Conclusion
	References
8 IR Liver-Directed Therapies for HCC
	1 Introduction
	2 Directed Energy Techniques
		2.1 Radiofrequency Ablation (RFA)
		2.2 Microwave Ablation (MWA)
		2.3 Cryoablation
		2.4 Irreversible Electroporation (IRE)
		2.5 Vascular Intervention
		2.6 Transarterial Chemoembolization (TACE)
		2.7 Drug-Eluting Beads (DEB-TACE)
		2.8 Transarterial Embolization (Bland Embolization) (TAE)
		2.9 Transarterial Radioembolization (TARE)
	3 Combination Therapies
	4 Future Locoregional Therapies
	5 Conclusion
	References
9 Clinical Presentation, Diagnosis, and Management of Uncommon Liver Tumors
	1 Primary Hepatic Angiosarcoma (PHA)
		1.1 Clinical Presentation
		1.2 Diagnosis
		1.3 Management
	2 Hepatic Epithelioid Hemangioendothelioma (HEH)
		2.1 Clinical Presentation
		2.2 Diagnosis
		2.3 Management
	3 Undifferentiated Embryonal Sarcoma (UESL)
		3.1 Clinical Presentation
		3.2 Diagnosis
		3.3 Management
	4 Combined Hepatocellular and Cholangiocarcinoma (CHC)
		4.1 Clinical Presentation
		4.2 Diagnosis
		4.3 Management
	5 Hepatic Liposarcoma
		5.1 Clinical Presentation
		5.2 Diagnosis
		5.3 Management
	6 Primary Hepatic Lymphoma (PHL)
		6.1 Clinical Presentation
		6.2 Diagnosis
		6.3 Management
	7 Hepatic Rhabdomyosarcoma (RMS)
		7.1 Clinical Presentation
		7.2 Diagnosis
		7.3 Management
	8 Fibrolamellar HCC (FL-HCC)
		8.1 Clinical Presentation
		8.2 Diagnosis
		8.3 Management
	9 Adult Hepatoblastoma (HB)
		9.1 Clinical Presentation
		9.2 Diagnosis
		9.3 Management
	10 Hepatic Angiomyolipoma (AML)
		10.1 Clinical Presentation
		10.2 Diagnosis
		10.3 Management
	11 Bile Duct Adenoma (BDA)
		11.1 Clinical Presentation
		11.2 Diagnosis
		11.3 Management
	12 Biliary Cystadenoma
		12.1 Clinical Presentation
		12.2 Diagnosis
		12.3 Management
	References
10 Epidemiology, Pathogenesis, and Prognosis of Uncommon Liver Tumors
	1 Primary Hepatic Angiosarcoma (PHA)
		1.1 Introduction
		1.2 Epidemiology
		1.3 Pathogenesis and Histology
		1.4 Prognosis
	2 Hepatic Epithelioid Hemangioendothelioma (HEH)
		2.1 Introduction
		2.2 Epidemiology
		2.3 Pathogenesis and Histology
		2.4 Prognosis
	3 Undifferentiated Embryonal Sarcoma (UESL)
		3.1 Introduction
		3.2 Epidemiology
		3.3 Pathogenesis and Histology
		3.4 Prognosis
	4 Combined Hepatocellular and Cholangiocarcinoma (CHC)
		4.1 Introduction
		4.2 Epidemiology
		4.3 Pathogenesis and Histology
		4.4 Prognosis
	5 Hepatic Liposarcoma
		5.1 Introduction
		5.2 Epidemiology
		5.3 Pathogenesis and Histology
		5.4 Prognosis
	6 Primary Hepatic Lymphoma (PHL)
		6.1 Introduction
		6.2 Epidemiology
		6.3 Pathogenesis and Histology
		6.4 Prognosis
	7 Hepatic Rhabdomyosarcoma (RMS)
		7.1 Introduction
		7.2 Epidemiology
		7.3 Pathogenesis and Histology
		7.4 Prognosis
	8 Fibrolamellar HCC (FL-HCC)
		8.1 Introduction
		8.2 Epidemiology
		8.3 Pathogenesis and Histology
		8.4 Prognosis
	9 Adult Hepatoblastoma (HB)
		9.1 Introduction
		9.2 Epidemiology
		9.3 Pathogenesis and Histology
		9.4 Prognosis
	10 Hepatic Angiomyolipoma (AML)
		10.1 Introduction
		10.2 Epidemiology
		10.3 Pathogenesis and Histology
		10.4 Prognosis
	11 Bile Duct Adenoma (BDA)
		11.1 Introduction
		11.2 Epidemiology
		11.3 Pathogenesis and Histology
		11.4 Prognosis
	12 Biliary Cystadenoma
		12.1 Introduction
		12.2 Epidemiology
		12.3 Pathogenesis and Histology
		12.4 Prognosis
	References
11 Treatment of Liver Metastases from Colorectal Cancer
	1 Introduction
	2 Prognostic Factors
		2.1 Patient Factors
		2.2 CEA
		2.3 Synchronous Versus Metachronous Presentation
		2.4 Tumor Burden
		2.5 Genetic Mutations
		2.6 Estimating Risk
	3 Preoperative Management
		3.1 Imaging
		3.2 Resectability
		3.3 Systemic Chemotherapy
		3.4 Locoregional Therapies
	4 Surgical Approach
		4.1 Simultaneous Versus Staged Resection for Synchronous Disease
		4.2 Minimally Invasive Surgery
		4.3 Parenchymal-Sparing Hepatectomy
		4.4 Radiofrequency and Microwave Ablation
		4.5 Two-Stage Hepatectomy
		4.6 Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS)
	5 Surveillance and Follow-Up
	References
12 Treatment of Isolated Liver Metastasis from Non-colorectal Cancer
	1 Introduction
	2 Neuroendocrine Liver Metastases
		2.1 Background
		2.2 Perioperative Considerations
			2.2.1 Carcinoid Disease
			2.2.2 Patient Selection
		2.3 Management of Metastatic Neuroendocrine Tumors
			2.3.1 Hepatic Resection
			2.3.2 Transcatheter Embolization
			2.3.3 Thermal Ablation
			2.3.4 Hepatic Transplantation
	3 Non-Colorectal Non-Neuroendocrine Liver Metastases
		3.1 Series Evaluating Multiple Metastatic Tumor Types
		3.2 Series Evaluating Single Metastatic Tumor Type
			3.2.1 Breast Cancer
			3.2.2 Lung Cancer
			3.2.3 Genitourinary Cancers
				Renal Cell Carcinoma
				Adrenocortical Carcinoma
			3.2.4 Reproductive Tract Cancers
				Testicular Cancer
				Ovarian Cancer
				Uterine Cancer
			3.2.5 Non-Colorectal Gastrointestinal Cancers
				Gastric Cancer
			3.2.6 Sarcoma
		3.3 Minimally Invasive Liver Surgery for Non-Colorectal Non-Neuroendocrine Liver Metastases
		3.4 Thermal Ablation for Non-Colorectal Non-Neuroendocrine Liver Metastases
	4 Conclusion
	References
Part II: Bile Duct Malignancies
	13 Diagnosis and Evaluation of Cholangiocarcinoma
		1 Introduction
		2 Intrahepatic Cholangiocarcinoma
			2.1 Signs and Symptoms
			2.2 Laboratory Tests and Tumor Markers
			2.3 Imaging
			2.4 Tissue Acquisition
		3 Perihilar Cholangiocarcinoma
			3.1 Signs and Symptoms
			3.2 Laboratory Tests and Tumor Markers
			3.3 Imaging
			3.4 Tissue Acquisition
		4 Distal Cholangiocarcinoma
			4.1 Signs and Symptoms
			4.2 Laboratory Tests and Tumor Markers
			4.3 Imaging
			4.4 Tissue Acquisition
		5 Primary Sclerosing Cholangitis and Cholangiocarcinoma
		6 General Tissue Acquisition Techniques
		7 Molecular Diagnosis
		8 Cholangiocarcinoma Staging
		9 Mimickers of Cholangiocarcinoma
			9.1 Primary Sclerosing Cholangitis
			9.2 IgG4-Related Sclerosing Cholangitis
			9.3 Inflammatory Pseudotumor
			9.4 Eosinophilic Cholangitis
			9.5 Mirizzi Syndrome
			9.6 Ischemic Cholangiopathy
			9.7 AIDS Cholangiopathy
			9.8 Hepatobiliary Sarcoidosis
			9.9 Biliary Adenoma
			9.10 Biliary Hamartoma
			9.11 Recurrent Pyogenic Cholangitis
			9.12 Portal Biliopathy/Cavernous Transformation of the Portal Vein
			9.13 Hepatocellular Carcinoma
			9.14 Adenomyosis of the Bile Ducts
			9.15 Pancreatic Cancer
			9.16 Metastatic Disease
			9.17 Carcinoma of the Gallbladder
			9.18 Xanthogranulomatous Cholecystitis and Cholangitis
		10 Conclusion
		References
	14 Cholangiocarcinoma: Epidemiology, Pathogenesis, and Prognosis
		1 Introduction
		2 Epidemiology
			2.1 Gender
			2.2 Geographical Distribution
			2.3 Trends of Incidence
			2.4 Cholangiocarcinoma and Misclassification
		3 Risk Factors
			3.1 Parasitic Infections
			3.2 Hepatitis B, Hepatitis C, and Cirrhosis
			3.3 Biliary Stone Disease
			3.4 Biliary Cysts
			3.5 Primary Sclerosing Cholangitis
			3.6 Metabolic Disorders
			3.7 Toxin Exposure
			3.8 Genetic Diseases
		4 Pathogenesis
			4.1 Inflammation and Cholestasis
			4.2 Inflammatory Mediators, Cytokines, and Growth Factors
			4.3 Inducible Nitric Oxide Synthase (iNOS) and Reactive Nitrogen Oxygen Species (RNOS)
			4.4 Developmental Pathways
			4.5 Tumor Microenvironment
			4.6 Genetic Alterations
		5 Staging and Classification System
			5.1 Bismuth-Corlette System
			5.2 Memorial Sloan Kettering Cancer Center (MSKCC) Classification System
			5.3 AJCC/UICC TNM Staging System
				5.3.1 Intrahepatic Cholangiocarcinoma and Validation of the AJCC Staging System
				5.3.2 Hilar Cholangiocarcinoma and Validation of the AJCC Staging System
				5.3.3 Distal Cholangiocarcinoma and Validation of the AJCC Staging System
		6 Prognosis and Outcomes
			6.1 Surgical Outcome: Resection-Related Prognosis
				6.1.1 Intrahepatic Cholangiocarcinoma
					R0 Survival
					R0 Recurrence
				6.1.2 Extrahepatic Cholangiocarcinoma
					R0 Survival
					R0 Recurrence
			6.2 Tumor-Related Prognosis
				6.2.1 Intrahepatic Cholangiocarcinoma and Survival
					Growth Patterns
					T Category-Based Prognostic Factors
					N Category-Based Prognostic Factors
					M Category-Based Prognosis
					Microscopic Features of Prognosis
					Tumor Location
					Molecular Factors
				6.2.2 Intrahepatic Cholangiocarcinoma and Recurrence
				6.2.3 Prognosis of Hilar Cholangiocarcinoma
					Macroscopic Growth Patterns
					T Category-Based Prognosis
					N Category-Based Prognosis
					M Category-Based Prognosis
					Microscopic Features of Prognosis
					Molecular Factors
				6.2.4 Hilar Cholangiocarcinoma and Recurrence
				6.2.5 Distal Cholangiocarcinoma and Survival
					T Category-Based Prognostic Factors
					N Category-Based Prognostic Factors
					M Category-Based Prognosis
					Microscopic Features of Prognosis
					Tumor Location
				6.2.6 Distal Cholangiocarcinoma and Recurrence
		References
	15 The Pathophysiology and Pathology of Intrahepatic and Extrahepatic Cholangiocarcinomas
		1 Introduction
		2 Intrahepatic Cholangiocarcinomas
		3 Clinical Features
		4 Gross Appearance
		5 Microscopic Description
		6 Diagnostic Criteria and Differential Diagnosis
		7 Cytology
		8 Molecular Pathology
		9 Pathological Classification and Staging (pTNM)
		10 Prognosis
		11 Carcinoma of the Extrahepatic Bile Ducts
		12 Clinical Features
		13 Gross Appearance
		14 Microscopic Description
		15 Diagnostic Criteria and Differential Diagnosis
		16 Cytology
		17 Molecular Pathology
		18 Pathological Classification and Staging (pTNM)
			18.1 Perihilar/Proximal Bile Ducts
			18.2 Distal Extrahepatic Bile Ducts
		19 Prognosis
		References
	16 Nonsurgical Management of Cholangiocarcinoma
		1 Introduction
		2 Locoregional Therapy
			2.1 Radiotherapy
			2.2 Liver-Directed Therapy
		3 Cytotoxic Chemotherapy
			3.1 Adjuvant Chemotherapy
			3.2 Chemotherapy for Advanced Unresectable and Metastatic Disease
		4 Targeted Therapy
			4.1 Genomic Profiling and Molecular Classification of Cholangiocarcinoma
			4.2 IDH Mutations
			4.3 FGFR Rearrangements and Fusions
			4.4 BRAF V600E Mutations
		5 Immunotherapy
		6 Conclusions and Future Directions
		References
	17 Surgical Treatment of Intrahepatic Cholangiocarcinoma
		1 Introduction
		2 Preoperative Evaluation: Resectability
		3 Staging Laparoscopy
		4 Lymphadenectomy
		5 Resection Margin Status
		6 Recurrence
		7 Minimally Invasive Surgery
		8 Liver Transplantation
		References
	18 Endoscopic Palliative Management of Cholangiocarcinoma
		1 Introduction
		2 ERCP Drainage with Biliary Stenting
		3 Endoscopic Ultrasound (EUS)-Guided Biliary Drainage
		4 ERCP-Directed Photodynamic Therapy (PDT)
		5 ERCP-Guided Radiofrequency Ablation (RFA)
		6 PDT Versus RFA
		7 ERCP-Guided Brachytherapy or Intraluminal Brachytherapy (ILBT)
		8 Conclusion
		References
19 Rare Tumors of the Bile Ducts
	1 Biliary Adenofibromas
	2 Bile Duct Adenoma
	3 Adenomyomas and Adenomyomatous Hyperplasia
	4 Ciliated Hepatic Foregut Cysts
	5 Cystadenoma and Cystadenocarcinoma
	6 Granular Cell Tumor
	7 Von Meyenburg Complexes
	8 Schwannoma
	9 Traumatic Neuroma
	10 Intraductal Papillary Neoplasia of the Bile Duct
	11 Embryonal Rhabdomyosarcoma
	12 Lymphoma
	13 Melanoma
	14 Carcinoid
	15 Paraganglioma
	16 Squamous Cell Carcinoma
	17 Conclusion
	18 High Yield Points
	References
Part III: Gallbladder Cancer
	20 Diagnosis and Evaluation of Gallbladder Cancer
		1 Epidemiology and Etiological Factors of Gallbladder Cancer
		2 Diagnosis and Staging of Gallbladder Cancer
		3 Surgical Treatment
		4 Extensive Lymphadenectomy
		5 Oncologic Approach
		6 Timing of Margin-Clearing Surgery for Incidental Gallbladder Cancer
		7 Port Site Resection
		References
	21 Pathogenesis, Epidemiology, and Prognosis of Gallbladder Cancer
		1 Introduction
		2 Epidemiology
		3 Pathogenesis
		4 Genetic Pathogenesis
		5 Exposures Pathogenesis
		6 Prognosis
		References
	22 Pathology of Gallbladder Carcinoma
		1 Introduction
		2 Clinical Features
			2.1 Gross Appearance
			2.2 Microscopic Description
		3 Diagnostic Criteria and Differential Diagnosis
		4 Molecular Pathology
		5 Pathological Classification and Staging (pTNM)
			5.1 Prognosis
		6 Conclusion
		7 Cross-References
		References
23 Nonsurgical Management of Gallbladder Cancer
	1 Introduction
	2 Adjuvant Therapy for GBC
	3 Locally Advanced/Unresectable GBC
		3.1 Systemic Therapy
		3.2 Brachytherapy and External Beam Radiation therapy
		3.3 Stereotactic Body Radiation Therapy (SBRT)
	4 Systemic Management of Metastatic Disease
		4.1 Chemotherapy
		4.2 Precision Medicine and Immunotherapy
	5 Summary
	References
Part IV: Pancreatic Malignancies
	24 Approach to the Patient with a Pancreatic Mass
		1 Introduction
		2 Differential Diagnosis for Pancreatic Masses
			2.1 Cystic Lesions
			2.2 Solid Exocrine/Space Occupying Masses
				2.2.1 Benign
			2.3 Autoimmune Pancreatitis (AIP)
				2.3.1 Chronic Pancreatitis (CP)
				2.3.2 Malignant
			2.4 Pancreatic Ductal Adenocarcinoma (PDAC)
				2.4.1 Solid Pseudopapillary Epithelial Neoplasm (SPEN)
				2.4.2 Acinar Cell Carcinoma (ACC)
					Primary Pancreatic Lymphoma (PPL)
				2.4.3 Pancreatoblastoma
				2.4.4 Metastases
			2.5 Solid Endocrine Lesions
				2.5.1 Neuroendocrine Tumor (NET)
		3 General Considerations for Diagnosis of a Pancreatic Mass
		4 Algorithm
		5 Conclusion
		References
	25 Evaluation and Management of the Patient with a Pancreatic Cyst
		1 Introduction
			1.1 Types of Pancreatic Cysts (Classification of Pancreatic Cysts)
			1.2 Non-neoplastic Cysts
		2 Pancreatic Pseudocysts (PPs)
			2.1 Management of Pancreatic Pseudocysts (PPs)
			2.2 Pancreatic Cystic Neoplasms
			2.3 Intraductal Papillary Mucinous Neoplasms (IPMNs)
		3 Diagnosis
		4 Treatment
		5 Surveillance of Mucinous Cysts (IMPN and MCN)
		6 Mucinous Cystic Neoplasms (MCNs)
		7 Serous Cystic Neoplasms (SCNs): Serous Cystadenoma (SCA)
		8 Solid Pseudopapillary Neoplasms (SPNs)
		9 Cystic Pancreatic Neuroendocrine Tumors (cPNETs)
		References
	26 Diagnosis and Evaluation of Pancreatic and Periampullary Adenocarcinoma
		1 Introduction
		2 Symptoms
			2.1 PDAC
				2.1.1 Pain
				2.1.2 Weight Loss
				2.1.3 Diabetes Mellitus
			2.2 Ampullary Cancer
		3 Risk Factors
			3.1 PDAC
				3.1.1 Pancreatic Intraepithelial Neoplasia (PanIN)
				3.1.2 Smoking
				3.1.3 Alcohol
				3.1.4 Diet
				3.1.5 Obesity
				3.1.6 Diabetes
				3.1.7 Pancreatitis
				3.1.8 Familial
			3.2 Inherited Cancer Syndromes
				3.2.1 Hereditary Pancreatitis
				3.2.2 Peutz-Jeghers Syndrome (PJS)
				3.2.3 Familial Atypical Malignant Mole and Melanoma Syndrome
				3.2.4 Hereditary Breast and Ovarian Cancer (HBOC) Syndrome
				3.2.5 Hereditary Non-polyposis Colorectal Cancer (HNPCC)
			3.3 Ampullary Cancer
		4 Screening
			4.1 PDAC
			4.2 Ampullary Cancer
		5 Diagnostic Workup
		6 Labs
		7 Imaging
			7.1 Transabdominal Ultrasound
			7.2 Computed Tomography (CT)
				7.2.1 PDAC
				7.2.2 Ampullary Cancer
			7.3 Magnetic Resonance Imaging (MRI) and Magnetic Resonance Cholangiopancreatography (MRCP)
				7.3.1 PDAC
				7.3.2 Ampullary Cancer
			7.4 Position Emission Tomography (PET)
		8 Endoscopic Evaluation
			8.1 Esophagogastroduodenoscopy (EGD)
			8.2 Endoscopic Retrograde Cholangiopancreatography (ERCP)
			8.3 Endoscopic Ultrasound (EUS)
		9 Tissue Acquisition
			9.1 PDAC
				9.1.1 Is Biopsy Necessary to Make the Diagnosis?
			9.2 Ampullary Cancer
			9.3 Interventional Radiology (IR)-Guided Biopsy
				9.3.1 PDAC
			9.4 EGD with Biopsies
				9.4.1 PDAC
				9.4.2 Ampullary Cancer
			9.5 ERCP
				9.5.1 PDAC
				9.5.2 Ampullary Cancer
			9.6 Endoscopic Ultrasound (EUS)
				9.6.1 PDAC
				9.6.2 Ampullary Cancer
		10 Staging
			10.1 PDAC
			10.2 Ampullary Cancer
		11 Conclusion
		References
	27 Pathogenesis, Epidemiology, and Prognosis of Pancreatic Adenocarcinomas
		1 Introduction
		2 Pathogenesis of Pancreatic Adenocarcinoma
			2.1 Cell Injury and Susceptibility Genes (PRSS1, SPINK1, CFTR)
			2.2 Cell Growth (KRAS, TP53, ATM, CHEK2, CDKN2A, STK11)
			2.3 DNA Repair (BRCA1, BRCA2, PALB2, MMR Genes)
			2.4 Cell Mobility and Adhesion (PALLD, APC)
			2.5 Molecular Biology and Carcinogenesis of Pancreatic Adenocarcinoma
			2.6 Noninvasive Pancreatic Neoplasia
				2.6.1 PanIN Progression
				2.6.2 Intraductal Papillary Mucinous Neoplasm (IPMN)
			2.7 Microenvironment of Pancreatic Adenocarcinoma
		3 Epidemiology of Pancreatic Adenocarcinoma
			3.1 Incidence in the USA
			3.2 Global Incidence and Mortality
			3.3 Etiology/Risk Factors
			3.4 Modifiable Risk Factors
				3.4.1 Smoking
				3.4.2 Alcohol
				3.4.3 Obesity
				3.4.4 Diet
				3.4.5 Occupational Exposures
			3.5 Non-modifiable Risk Factors
				3.5.1 Age
				3.5.2 Gender
				3.5.3 Ethnicity
				3.5.4 Diabetes
				3.5.5 Chronic Pancreatitis
				3.5.6 Hereditary Conditions/Genetics
				3.5.7 Miscellaneous Risk Factors
		4 Prognosis
		References
	28 Pathology of Pancreatic Ductal Adenocarcinoma
		1 Introduction
		2 Macroscopy and Gross Examination of Pancreatic Ductal Adenocarcinoma
		3 Histopathology of Pancreatic Ductal Adenocarcinoma
		4 Histological Subtypes of Pancreatic Ductal Adenocarcinoma
			4.1 Colloid Carcinoma
			4.2 Adenosquamous Carcinoma and Squamous Cell Carcinoma
			4.3 Medullary Carcinoma
			4.4 Hepatoid Carcinoma
			4.5 Large Ductal-Type Carcinoma
			4.6 Signet-Ring Cell Carcinoma
			4.7 Undifferentiated Carcinoma
			4.8 Undifferentiated Carcinoma with Osteoclast-Like Giant Cells
			4.9 Invasive Micropapillary Carcinoma
		5 Immunohistochemistry
		6 Evaluation of Resection Margins
		7 Pathologic Stage Classification
			7.1 Primary Tumor (pT)
			7.2 Regional Lymph Nodes (pN)
			7.3 Distant Metastasis (pM)
		8 Pathology of Neoadjuvant Treated Pancreatic Adenocarcinoma
		9 Cytopathology of Pancreatic Adenocarcinoma
			9.1 Pancreatic Cytopathology Sample Collection
			9.2 Cytopathology Smear Artifacts
			9.3 Normal Cytopathologic Components of Pancreatic FNAs
			9.4 Cellular Contaminants of Pancreatic FNAs
			9.5 Pancreatic Ductal Adenocarcinoma Cytopathology
		10 Precursors of Pancreatic Ductal Adenocarcinoma
			10.1 Pancreatic Intraepithelial Neoplasia
			10.2 Pancreatic Intraductal Papillary Mucinous Neoplasm
			10.3 Pancreatic Intraductal Oncocytic Papillary Neoplasm
			10.4 Pancreatic Intraductal Tubulopapillary Neoplasm
			10.5 Pancreatic Mucinous Cystic Neoplasm
		11 Molecular Pathology of Pancreatic Ductal Adenocarcinoma
			11.1 Epithelial-to-Mesenchymal Transition
			11.2 Molecular Profiling for Pancreatic Cancer Risk Stratification
		References
	29 Reducing the Risk of and Screening for Pancreatic Cancer
		1 Introduction
		2 What Is the Goal of Pancreatic Cancer Screening?
		3 What Are the Benefits of Pancreatic Cancer Screening?
		4 Who Should Undergo Screening and Surveillance?
			4.1 Hereditary Pancreatitis
			4.2 Peutz-Jeghers Syndrome
			4.3 Hereditary Breast-Ovarian Cancer Syndrome
			4.4 Familial Atypical Multiple Mole and Melanoma Syndrome
		5 Hereditary Nonpolyposis Colorectal Cancer (HNPCC) or Lynch Syndrome
		6 Ataxia-Telangiectasia
		7 Familial Pancreatic Cancer
		8 At What Age Should Screening Start?
		9 How to Screen for Pancreatic Cancer?
		10 Genetic Testing
		11 Timing of Surveillance
		12 What to Do with the Findings from Screening and Surveillance Examinations?
		13 Role of Surgery
		14 For Individuals Who Do Not Meet the Criteria for Surgery
		15 Reducing the Risk
		16 Risks of Screening
		17 Newer Screening and Surveillance Modalities
		18 Conclusion
		References
	30 Nonsurgical Management of Pancreatic Adenocarcinoma
		1 Introduction
		2 Systemic Therapy for Unresectable or Metastatic Disease
		3 Chemoradiation for Locally Advanced Unresectable Disease
		4 Adjuvant Chemotherapy and Radiation in Resectable Disease
		5 Adjuvant Chemotherapy in Resectable Disease
		6 Adjuvant Radiation in Resectable Disease
		7 Neoadjuvant Therapy in Borderline Resectable Disease
		8 Radiation in Borderline Resectable Disease
		9 Neoadjuvant Chemotherapy and Radiation in Resectable Disease
		10 Palliative Radiation for Metastatic Disease
		11 Systemic Therapy Regimens for Pancreatic Cancer
		12 Radiation Techniques for Pancreatic Cancer
		13 External Beam Radiation Simulation
		14 Target Definitions Contouring: (NRG Contouring Atlas) [74]
		15 Dose Constraints for Conventional Radiation
		16 Stereotactic Body Radiation (SBRT)
			16.1 SBRT Simulation
			16.2 Dose Constraints for SBRT
		17 Intraoperative Radiation
		18 Side Effects of Radiation
		19 Conclusion
		20 Cross-References
		References
	31 Surgical Management of Pancreatic Adenocarcinoma
		1 Introduction
		2 Interventions Prior to Resection
		3 Surgical Technique: Minimally Invasive Staging Techniques
		4 Biliary Drainage
		5 Preoperative Management
		6 Operative Techniques
			6.1 Pancreaticoduodenectomy
		7 Abdominal Exploration
		8 Tumor Resection
		9 Reconstruction
		10 Alternative Pancreaticoduodenectomy Techniques
		11 Appleby Procedure
		12 Vascular Reconstruction
		13 Postoperative Complications
			13.1 Delayed Gastric Emptying
			13.2 Post-pancreatectomy Hemorrhage
		14 Palliative Surgery for Pancreatic Adenocarcinoma
			14.1 Celiac Plexus Neurolysis
			14.2 Biliary Bypass
		15 Conclusion
		References
	32 Intraoperative Radiation Treatment
		1 Introduction
		2 Historical Perspective
		3 Key Studies
			3.1 Resectable Disease
			3.2 Locally Advanced and Unresectable Disease
			3.3 Locally Recurrent Disease
			3.4 Neoadjuvant Therapy
		4 Contraindications
		5 Technique
			5.1 Target Areas
			5.2 Radiation Dose
			5.3 IORT Energy
			5.4 MGH Technique
		6 Advantages and Disadvantages of IORT
		7 Complications and Mortality
			7.1 Gastroparesis
			7.2 Gastrointestinal Hemorrhage
			7.3 Radiation Myelopathy
		8 Conclusions
		References
	33 Palliative Endoscopic Therapy of Pancreatic Duct Adenocarcinoma (PDAC)
		1 Introduction
		2 Palliative Care of Biliary Obstruction
			2.1 Palliation with Stents
				2.1.1 Plastic Stents
				2.1.2 Self-Expanding Metal Stents
				2.1.3 Stent Placement
				2.1.4 Resource Utilization
			2.2 Comparative Data
			2.3 Stent Dysfunction
			2.4 Biliary Ablation for Patency
			2.5 Tumor Ablation Therapies
			2.6 Endoscopic Failures
		3 Gastroduodenal Obstruction
			3.1 Stent Technique
			3.2 Alternatives to Gastroduodenal Stent Placement
			3.3 Afferent Limb Syndrome
		4 Pain
		5 Future Directions
		6 Conclusion
		References
34 Diagnosis and Management of Pancreatic Neuroendocrine Tumors and Other Rare Pancreatic Neoplasms
	1 Introduction
	2 Pancreatic Neuroendocrine Tumors
		2.1 Background
		2.2 Diagnosis
	3 CT/MRI
	4 Endoscopic Ultrasound (EUS)
	5 Somatostatin Receptor Scintigraphy (SRS)
	6 Venous Hormone Sampling
	7 Tumor Markers
		7.1 Treatment
	8 Surgical Resection/Ablation
	9 Traditional Surgical Approaches
	10 Pancreas Parenchymal-Sparing Procedures
	11 Surgical Management of Advanced Disease
	12 Surgical Management of Metastatic Liver Disease
	13 Other Liver-Localizing Therapies
	14 Liver Transplantation
	15 Medical Management
	16 Chemotherapy
	17 Somatostatin Analogs
	18 Interferon Alpha
	19 Molecular Targeted Therapy
	20 Peptide Receptor Radionuclide Therapy (PRRT)
	21 Future Approaches
	22 PNET-Specific Diagnosis and Treatment
	23 Insulinoma
	24 Gastrinoma (Zollinger-Ellison Syndrome)
	25 Glucagonomas
	26 VIPomas
	27 Somatostatinomas
	28 GRFomas
	29 Nonfunctional Pancreatic Neuroendocrine Tumors (NF-pNETs)
	30 Other Rare Pancreatic NETs
	31 MEN1
	32 Pancreatic Cystic Neoplasms
	33 Squamous and Adenosquamous Cell Carcinomas
	34 Acinar Cell Carcinoma
	35 Pancreatic Lymphoma
	36 Pancreatic Schwannoma
	37 Pancreatoblastoma
	38 Conclusion
	References
35 Epidemiology, Pathogenesis, and Prognosis of Pancreatic Neuroendocrine Tumors
	1 Introduction
	2 Epidemiology
	3 Classification: Functional Versus Nonfunctional Tumors
		3.1 Functional Pancreatic NETs
	4 Grading
	5 Pathogenesis
		5.1 Chromatin Remodeling Pathway
		5.2 TP53/Rb Pathway
		5.3 PI3K/AKT/mTOR Pathway
	6 Staging
		6.1 AJCC Eighth Staging for Pancreatic NETs AJCC Eighth Staging for G3 Pancreatic NETs
		6.2 AJCC Eighth and Pancreatic G1-G2 NET Prognostic Stage Groups [65]
		6.3 AJCC Eighth and Pancreatic G3 NET Prognostic Stage Groups [65]
		6.4 Validation of the Eighth AJCC Guideline
	7 Survival
		7.1 Metastatic Disease
		7.2 Tumor Functionality
		7.3 Tumor Location
		7.4 Age of Onset
		7.5 Role of mTOR Inhibitor in Survival
	8 Conclusion
	References
36 Pathology of Pancreatic Neuroendocrine Tumors
	1 Introduction
	2 Classification and General Characteristics of Neuroendocrine Neoplasms of the Pancreas
		2.1 Pancreatic Neuroendocrine Neoplasms: Updated WHO Classification
		2.2 PanNEN Staging
		2.3 Diagnostic Criteria
	3 Fine-Needle Aspiration Cytology (FNAC) and Papanicolaou Society of Cytopathology Guidelines for Risk Stratification of Neuro...
	4 Non-functioning Pancreatic Neuroendocrine Tumors
		4.1 Epidemiology and Clinical Features
		4.2 Macroscopy/Macroscopic Features
		4.3 Cytology/Cytologic Features
		4.4 Histopathology/Histopathologic Features and Differential Diagnosis
		4.5 Genetic and Molecular Concepts, Prognosis, and Prediction
	5 Pancreatic Neuroendocrine Carcinoma (PanNEC)
		5.1 Epidemiology and Clinical Features
		5.2 Macroscopy/Macroscopic Features
		5.3 Cytology/Cytologic Features
		5.4 Histology/Histopathologic Features and Differential Diagnosis
		5.5 Genetic and Molecular Concepts, Prognosis, and Prediction
	6 Pancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasms (PanMiNENs)
		6.1 Epidemiology and Clinical Features
		6.2 Macroscopy/Macroscopic Features
		6.3 Cytology/Cytologic Features
		6.4 Histology/Histopathologic Features and Differential Diagnosis
		6.5 Genetic and Molecular Concepts, Prognosis, and Prediction
	7 Functioning Pancreatic Neuroendocrine Neoplasms (F-PanNENs)
		7.1 Insulinoma
			7.1.1 Epidemiology and Clinical Features
			7.1.2 Macroscopy/Macroscopic Features
			7.1.3 Cytology/Cytologic Features
			7.1.4 Histopathology and Differential Diagnosis
			7.1.5 Genetic and Molecular Concepts, Prognosis, and Prediction
		7.2 Gastrinoma
			7.2.1 Epidemiology and Clinical Features
			7.2.2 Macroscopy/Macroscopic Features
			7.2.3 Cytology/Cytologic Features
			7.2.4 Histopathology/Histopathologic Features and Differential Diagnosis
			7.2.5 Genetic and Molecular Concepts, Prognosis, and Prediction
		7.3 VIPoma
			7.3.1 Epidemiology and Clinical Features
			7.3.2 Macroscopy/Macroscopic Features
			7.3.3 Cytology/Cytologic Features
			7.3.4 Histopathology/Histopathologic Features and Differential Diagnosis
			7.3.5 Genetic and Molecular Concepts, Prognosis, and Prediction
		7.4 Glucagonoma
			7.4.1 Epidemiology and Clinical Features
			7.4.2 Macroscopy/Macroscopic Features
			7.4.3 Histopathology/Histopathologic Features
			7.4.4 Cytology/Cytologic Features
			7.4.5 Genetic and Molecular Concepts, Prognosis, and Prediction
		7.5 Somatostatinoma
			7.5.1 Epidemiology and Clinical Features
			7.5.2 Macroscopy/Macroscopic Features
			7.5.3 Cytology/Cytologic Features
			7.5.4 Histopathology/Histopathologic Features and Differential Diagnosis
		7.6 ACTH-Producing Pancreatic Neuroendocrine Tumor
			7.6.1 Epidemiology and Clinical Features
			7.6.2 Macroscopy/Macroscopic Features
			7.6.3 Cytology/Cytologic Features
			7.6.4 Histology/Histopathologic Features and Differential Diagnosis
		7.7 Serotonin-Producing Pancreatic Neuroendocrine Tumor
			7.7.1 Epidemiology and Clinical Features
			7.7.2 Macroscopy/Macroscopic Features
			7.7.3 Cytology/Cytologic Features
			7.7.4 Histopathology/Histopathologic Features and Differential Diagnosis
		7.8 Pancreatic Polypeptide Cell Pancreatic Endocrine Tumor
			7.8.1 Epidemiology and Clinical Features
			7.8.2 Macroscopy/Macroscopic Features
			7.8.3 Cytology/Cytologic Features
			7.8.4 Histopathology/Histopathologic Features and Differential Diagnosis
		7.9 Functioning Pancreatic Neuroendocrine Tumor Prognosis
	References
37 Non-surgical Management of Pancreatic Neuroendocrine Tumors (PNETs)
	1 Introduction and Epidemiology
	2 Pathological Classification, Functional vs Non-functional
	3 Medical Management
	4 Surgical Management of PNET
	5 Insulinoma
	6 Gastrinoma
	7 Other F-PNETs
	8 Glucagonoma
	9 Somatostatin Therapy
	10 Lanreotide and Octreotide
	11 Pasireotide
	12 Interferon Therapy
	13 PNET Advanced Disease and Metastasis
	14 Surgical Management of PNET Metastasis
	15 Laparoscopic Radiofrequency Ablation
	16 Chemotherapy
		16.1 Temozolomide
		16.2 Streptozotocin
		16.3 Dacarbazine
		16.4 5-Fluorouracil
		16.5 Doxorubicin
		16.6 Platinum Compounds
	17 Predictive Biomarkers for Efficacy of Chemotherapy
	18 Precautions with Chemotherapy and COVID-19
	19 Management of Pancreatic Carcinoid Tumors and Precautions with Chemotherapy
	20 Trans-catheter Arterial Embolization (TAE) and Trans-catheter Arterial Chemoembolization (TACE) and Selective Internal Radi...
	21 Ablation Therapy
	22 Endoscopic Therapy
		22.1 EUS Radiofrequency Ablation
		22.2 EUS Alcohol Ablation
	23 Targeted Molecular Therapy
		23.1 mTOR Inhibitors
		23.2 VEGF Inhibitors
	24 Combined Everolimus and Sunitinib Therapy
	25 Immunotherapy
	26 Conclusion
	References
38 Surgical Management of Pancreatic Neuroendocrine Tumors (PNET)
	1 Introduction
	2 Evaluation
		2.1 Staging
	3 Grading
	4 Functional Pancreatic Neuroendocrine Tumors and Surgical Management
		4.1 Insulinoma
			4.1.1 Pathophysiology
			4.1.2 Clinical Presentation
			4.1.3 Workup
			4.1.4 Surgical Management
		4.2 Glucagonoma
			4.2.1 Pathophysiology
			4.2.2 Clinical Presentation
			4.2.3 Workup
			4.2.4 Surgical Management
		4.3 Gastrinoma
			4.3.1 Pathophysiology
			4.3.2 Clinical Presentation
			4.3.3 Workup
			4.3.4 Surgical Management
		4.4 Somatostatinoma
			4.4.1 Pathophysiology
			4.4.2 Clinical Presentation
			4.4.3 Workup
			4.4.4 Surgical Management
		4.5 VIPoma
			4.5.1 Pathophysiology
			4.5.2 Clinical Presentation
			4.5.3 Workup
			4.5.4 Surgical Management
	5 Specific Questions on Surgical Management of Pancreatic Neuroendocrine Tumors
		5.1 Surgical Management of Nonfunctional Pancreatic Neuroendocrine Tumors (PNET)
		5.2 Enucleation Versus Primary Resection
		5.3 Minimally Invasive Surgery
		5.4 Cytoreductive Surgery
		5.5 Surgery for High-Grade PNETS
		5.6 Lymph Node Dissection
		5.7 Liver Transplantation
	6 Surgical Management of Inherited Syndromes
		6.1 Multiple Endocrine Neoplasia Type 1 (MEN1)
		6.2 Von Hippel-Lindau (VHL)
		6.3 Neurofibromatosis Type 1 (NF1)
		6.4 Tuberous Sclerosis Complex (TSC)
	7 Conclusion
	References
39 Emerging Endoscopic Therapies for Pancreatic Neuroendocrine Tumors
	1 Introduction
	2 Classification
	3 Diagnosis
	4 Management
	5 Endoscopic Therapies for PNETs
		5.1 EUS-Guided Ethanol Ablation
		5.2 EUS-Guided Radiofrequency Ablation
		5.3 EUS-Guided Photodynamic Therapy
		5.4 Other Investigational EUS-Guided Therapies
	6 Conclusion
	References
Part V: Emerging And Future Trends In Managing Hepatobiliary And Pancreatic Malignancies
	40 Molecular and Genetic Profiling for the Diagnosis and Therapy of Hepatobiliary and Pancreatic Malignancies
		1 Introduction
		2 Molecular and Genetic Profiling
		3 Familial Pancreatic Cancer Genes
		4 Familiar Hepatobiliary Cancer Genes
		5 Genetic Counseling
		6 Diagnosis and Therapy of Biliary Tract Cancers
			6.1 FGFR Inhibitor in FGFR Fusion-Positive Cholangiocarcinoma
			6.2 IDH Inhibitor in IDH Mutated Cholangiocarcinoma
			6.3 BRAF and MEK Dual Inhibition in BRAF Mutated Cholangiocarcinoma
			6.4 HER2 Targeted Therapy in HER2 Overexpressed Cholangiocarcinoma
			6.5 TRK Inhibitor in TRK Fusion-Positive Cholangiocarcinoma
			6.6 Immunotherapy in Cholangiocarcinoma
		7 Diagnosis and Therapy of Pancreatic Cancer
			7.1 Platinum-Based Chemotherapy in BRCA1/2- or PALB2-Mutated Pancreatic Cancer
			7.2 Olaparib in BRCA1/2- or PALB2-Mutated Pancreatic Cancer
			7.3 Immunotherapy in Pancreatic Cancer
			7.4 Other Actionable Mutations in Pancreatic Cancer
			7.5 TRK Inhibitor in TRK Fusion-positive Pancreatic Cancer
		8 Diagnosis and Therapy of Hepatocellular Carcinoma
		9 Conclusion
		10 Cross-References
		References
41 Personalized Medicine for Patients with Liver, Biliary Tract, and Pancreatic Cancer
	1 Introduction
	2 Hepatocellular Carcinoma
		2.1 Targeted Therapy
		2.2 Immunotherapy
		2.3 Emerging Diagnostic, Predictive, and Prognostic Biomolecular Features
	3 Biliary Tract Malignancies
		3.1 Targeted Therapy
		3.2 Immunotherapy
		3.3 Emerging Diagnostic, Predictive, and Prognostic Biomolecular Features
	4 Pancreatic Adenocarcinoma
		4.1 Targeted Therapy
		4.2 Immunotherapy
		4.3 Emerging Diagnostic, Predictive, and Prognostic Biomolecular Features
	5 Pancreatic Neuroendocrine Neoplasms
		5.1 Targeted Therapy
		5.2 Immunotherapy
		5.3 Emerging Diagnostic, Predictive, and Prognostic Biomolecular Features
	6 Conclusion
	References
42 The Role of Robotic Surgery in Treating Hepatobiliary and Pancreatic Malignancies
	1 Introduction
	2 TilePro
	3 Iris
	4 Robotic Surgery for Hepatobiliary Malignancies
		4.1 Historical Perspective
		4.2 Current Status of Robotic Hepatectomy (RH) for Hepatobiliary Malignancies
			4.2.1 Outcome Comparison Between RH and Conventional Surgeries
			4.2.2 Quality of Life (QoL) and Cost-Effectiveness
	5 Robotic Surgery for Pancreatic Malignancies
		5.1 Current Status of Robotic Pancreatic Surgery
			5.1.1 Distal Pancreatectomy (DP)
				The Learning Curve of RDP
				RDP vs Open or LDP
			5.1.2 Robotic Pancreatoduodenectomy (RPD)
				RPD vs OPD
	6 Potentials of Robotics in HPB Surgery
	7 Conclusion
	References
43 The Multidisciplinary Approach to Managing Hepatobiliary and Pancreatic Malignancies and Its Importance
	1 Pancreatic Neuroendocrine Tumors (PNET)
		1.1 Introduction
		1.2 Diagnostic Approach
		1.3 MDT for PNET
			1.3.1 Surgery for PNET
			1.3.2 NELM: PNET with Liver Metastases
			1.3.3 Conclusion
	2 Pancreatic Cancer (PC)
		2.1 MDT (Multidisciplinary Treatment for Pancreatic Cancer (PC))
		2.2 Upfront Surgery
		2.3 Advocates of Presurgical Treatment
		2.4 Preoperative Radiation Therapy
		2.5 Surgical Management
			2.5.1 180-360 Isolated Encasement of the Superior Mesenteric Artery
			2.5.2 Venous Involvement
		2.6 The Evolution of Chemotherapy in the Era of MDT Management of PC
			2.6.1 Neoadjuvant Versus Adjuvant Chemotherapy +/-RT
			2.6.2 Perioperative Chemotherapy
		2.7 For Resectable PC
			2.7.1 Neoadjuvant Therapy
			2.7.2 Adjuvant Therapy
		2.8 Conclusion
	3 Multivisceral Resection for LAPC Invading the Transverse Mesocolon
	4 Preoperative Biliary Decompression on Painless Jaundice
	5 PC in Elderly Patients
		5.1 Multimodality Therapy
			5.1.1 Chemoradiation Only
			5.1.2 Palliation
			5.1.3 Hospice
	6 Hepatocellular Carcinoma (HCC)
		6.1 HCC
		6.2 Approach to HCC
		6.3 Liver Transplantation
		6.4 Liver Resection
		6.5 Locoregional Treatment for HCC: Ablation, Arterial Infusion, IRE, RT
			6.5.1 Arterial Infusion
			6.5.2 IRE
	7 Colorectal Liver Metastasis (MDT CRLM)
		7.1 Surgical Strategy in CRLM
		7.2 PVE
			7.2.1 Indications for PVE
			7.2.2 Contraindication for PVE
		7.3 Two-Stage Hepatectomy
		7.4 Intraoperative Strategy
		7.5 Targeted Therapy on CRLM
		7.6 EGFR Inhibition
		7.7 Re-resection After Recurrence
		7.8 Conclusion
	8 MDT Biliary Tract Cancers (BTC)
		8.1 Biliary Tract Cancer (BTC)
		8.2 Gallbladder Cancer
		8.3 Diagnostic Challenge
		8.4 Surgical Approach for Perihilar BTC
		8.5 Medical Oncology
		8.6 Conclusions
	9 Assessment of the Hypertrophy Response and Timing of Resection After Portal Vein Occlusion
		9.1 Communication Between Surgeon and IR for Optimal PVE
		9.2 Preoperative Biliary Drainage and PVE
	References
44 The Role of the Palliative Care Team in the Management of Hepatobiliary and Pancreatic Malignancies
	1 Introduction
	2 An Historical Perspective of the Palliative Care Movement
	3 Demystifying Palliative Care
	4 Palliative Care: Official Definitions
	5 Palliative Care: Approach to Hepatobiliary and Pancreatic Cancer
	6 Symptom Management
	7 Pain
	8 Pain Treatment
	9 Nausea
	10 Anorexia and Cachexia
	11 Fatigue
	12 Pruritus
	13 Hiccups
	14 Psychiatric Disorders in Advanced Cancer
	15 Spiritual and Existential Domains
	16 Advance Care Planning
	17 Conclusion
	References
45 Spiritual Thinking and Surgery
	1 Shamans, Scientists, and Hospitals
	2 Main Text
	3 Conclusion
	References
46 Integrative Medicine and Hepatobiliary and Pancreatic Cancer: What to Expect
	1 Introduction
	2 Diet and Exercise
	3 Nutritional Supplements
	4 Supplements to Avoid
		4.1 Probiotics and Prebiotics
	5 Mind-Body Practices
	6 Acupuncture
	7 Conclusions
	References
Index