Оглавление
Группа авторов. Clinical Pancreatology for Practising Gastroenterologists and Surgeons
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
Clinical Pancreatology for Practising Gastroenterologists and Surgeons
Contributors
Foreword
Preface
Dedication
1 Acute Pancreatitis: An Overview
Introduction
Causes
Laboratory Diagnosis
Imaging
Risk Stratification
Classification
Treatment
Prophylactic Antibiotics
Nutrition
Post‐discharge Cholecystectomy
Long‐term Sequelae
References
2 How to Deal with the Etiological Diagnosis of Acute Pancreatitis in Clinical Practice?
Introduction
Etiological Diagnosis. Gallstone‐induced Pancreatitis
Microlithiasis
Alcoholic Pancreatitis
Drug‐induced Pancreatitis
Other Etiological Diagnoses of Acute Pancreatitis. Hypercalcemia
Hypertriglyceridemia
Smoking
Type 2 Diabetes Mellitus
Pancreatobiliary Tumors
Post‐ERCP Pancreatitis
Single and Double Balloon Enteroscopy
Congenital Anomalies. Pancreas Divisum
Anomalous Pancreatobiliary Ductal Union
Choledochocele
Annular Pancreas
Idiopathic Acute Pancreatitis
Investigative Work‐up
Concluding Remarks
References
3 Definition of Complications and Severity of Acute Pancreatitis for Clinical Practice
Background
The Atlanta Classification 1992
The Revised Atlanta Classification 2012
Definition of Organ Failure and Complications in Acute Pancreatitis. Organ Failure
Local Complications
Acute Peripancreatic Fluid Collection
Pancreatic Pseudocyst
Acute Necrotic Collection
Walled‐off Necrosis
Systemic Complications
Definition of Severity in Acute Pancreatitis
Mild Acute Pancreatitis
Moderately Severe Acute Pancreatitis
Severe Acute Pancreatitis
Limitations of the Revised Atlanta Classification
The Determinant‐Based Classification
Conclusion
References
4 Early Prediction of Severity in Acute Pancreatitis : What can be Done in Clinical Practice?
Introduction
Available Prediction Tools. Volume Deficit
Inflammatory Response
Host‐related Characteristics. Age and Comorbidity Burden
Obesity and Hypertriglyceridemia
Degree of Parenchymal and Extra‐parenchymal Injury
Scoring Systems
Limitations and Future of Current Scoring Systems and Predictive Markers
Artificial Intelligence and Biomarkers: the Future?
References
5 Role of CT Scan in Acute Pancreatitis : When is it Indicated and What Information can be Obtained?
CT Imaging in Acute Pancreatitis
Confirming the Diagnosis of AP
Assessing the Etiology of Acute Pancreatitis
Assessing the Prognosis of Acute Pancreatitis
Identifying Local Complications Associated with Acute Pancreatitis. Pancreatic Necrosis and Peripancreatic Fluid Collections
Vascular Complications
Other Complications
Timing of CT in Acute Pancreatitis
Limitations of CT Imaging
Conclusion
Disclosures
References
6 Role of MRI in Acute Pancreatitis : When is it Indicated and What Information can be Obtained?
Introduction
MRI and MRCP Protocol for Pancreas Examination
Interstitial Edematous Pancreatitis
Necrotizing Pancreatitis
Complications of Acute Pancreatitis. Fluid Collections
Acute Peripancreatic Fluid Collection
Acute Necrotic Collection
Pseudocyst
Walled‐off Necrosis
Vascular Complications
References
7 Treatment of Acute Pancreatitis in The Emergency Room : What Should be Done During the First Hours of Disease?
Introduction
Early Diagnosis in the Emergency Room
Initial Work‐up for Etiology
Severity Assessment, Triage, and Disposition
Specialty Consultation
Management. First‐line Medical Management: Fluid Resuscitation
Type of Intravenous Fluid to Administer
Antibiotics
Pain Control
Nutrition
Summary
References
8 Acute Pancreatitis : A Practical Guideline for the Monitoring and Treatment of Systemic Complications
Introduction
Acute Pancreatitis and Systemic Complications: Definitions, Importance, and Incidence
Monitoring Respiratory Function and Management of Respiratory Failure
Shock: Volume Management and Hemodynamic Monitoring
Acute Renal Failure: Early Detection and Management
Other Systemic Complications Associated with Acute Pancreatitis. Hypocalcemia
Disseminated Intravascular Coagulation
Gastrointestinal Bleeding
Pancreatic Encephalopathy and Posterior Reversible Encephalopathy Syndrome
Abdominal Compartment Syndrome
References
9 Guidelines for the Treatment of Pain in Acute Pancreatitis
Introduction
Nonsteroidal Anti‐inflammatory Drugs
Opioid Analgesics
Epidural Analgesia
Local Anesthetics
Summary
References
10 Nutrition in the Acute Phase of Pancreatitis : Why, When, How and How Long?
Why
When
How
What to Feed
References
11 Oral Refeeding in Acute Pancreatitis : When and How Should it be Restarted?
Introduction
What is the Optimal Timing of Refeeding in AP?
How Should Oral Refeeding be Scheduled?
What are the Predictors of Oral Feeding Intolerance in AP Patients?
Summary and Recommendations
References
12 Pharmacological Therapy for Acute Pancreatitis : Any Light at the End of the Tunnel?
Introduction
Calcium Toxicity
Mitochondrial Dysfunction
Autophagy
Acinar Cell Secretion, Serine Proteases, and Serine Protein Kinases
Immune Cells/Inflammation
CFTR
Design of Future Clinical Trials
Conclusion
References
13 Indication and Optimal Timing of ERCP in Acute Pancreatitis
Introduction
ERCP in the Setting of Acute Biliary Pancreatitis
Urgent ERCP
Elective ERCP
Additional Applications of ERCP in the Setting of Acute Pancreatitis
Conclusions
Disclosures
References
14 How to Deal with Infected Pancreatic Necrosis?
Introduction
Prevention of Infection of (Peri)pancreatic Necrosis
Diagnosis of Infected (Peri)pancreatic Necrosis
How to Deal with Infected (Peri)pancreatic Necrosis
Systemic Antibiotics
Endoscopic or Percutaneous Drainage
Endoscopic or Laparoscopic Necrosectomy
References
15 Minimally Invasive Surgical Necrosectomy in Clinical Practice : Indications, Technical Issues, and Optimal Timing
Introduction
Percutaneous Drainage
Sinus Tract Endoscopy
Endoscopic (Endoluminal) Approach
Retroperitoneal Approach
Laparoscopic Transperitoneal Approach
References
Note
16 Endoscopic Necrosectomy in Clinical Practice : Indications, Technical Issues, and Optimal Timing
Introduction
Management of Symptomatic Pseudocysts
Management of Symptomatic Walled‐off Necrosis. Indications and Timing for Intervention
Choosing the Best Interventional Option: the Step‐up Approach
Methods of Endoscopic Necrosectomy and Stent Choice
Conclusion
References
17 Management of Acute Pancreatic Pseudocyst : When to Observe, When and How to Drain?
Introduction
Evaluation
Drainage Therapy
Disconnected Pancreatic Duct Syndrome
Complications
Conclusion
References
18 The Disconnected Main Pancreatic Duct Syndrome : How to Proceed in Clinical Practice?
Introduction
Epidemiology
Risk Factors and Predictors of DPDS
Clinical Significance
Clinical Presentation
Diagnosis
Treatment
Conclusions
References
19 Vasculature Complications in Pancreatitis : How to Deal with Them?
Venous Complications
Splanchnic Thrombosis Rates
Risk Factors for Thrombosis
Clinical Findings
Screening
Splenic Vein Thrombosis
Portal Vein Thrombosis
Management of Visceral Vein Thrombosis
Anticoagulation
Surgical Management
Miscellaneous Venous Complications. Bowel Wall Ischemia
Portal Vein–Pseudocyst Fistula
Arterial Complications
Pseudoaneurysm
Pseudoaneurysm and Risk of Rupture
Hemosuccus Pancreaticus
Imaging of Pseudoaneurysm or Potential Hemorrhage
Ruptured Pseudoaneurysm Management
Summary
References
20 Acute Relapsing Pancreatitis : What can be Done to Prevent Relapses?
Introduction
Definition
Burden
Demographics
Etiology
Diagnostic Work‐up
Natural History and Risk of Progression
Preventing Recurrences and Disease Progression
Conclusion
Acknowledgment
References
21 Diagnosis and Therapeutic Approach to Pancreatic Exocrine Insufficiency after Acute Pancreatitis
Introduction
Symptoms
Diagnosis
Management
Summary
References
22 Asymptomatic Chronic Elevation of Serum Pancreatic Enzymes: How to Deal with It?
Introduction
Physiology of Pancreatic Enzymes
Pancreatic Abnormalities in Patients with Pancreatic Hyperenzymemia
Pancreatic Hyperenzymemia: A Clue to Malignancy?
Pancreatic Abnormalities at Second‐level Imaging
Gastrointestinal Diseases and Pancreatic Hyperenzymemia. Inflammatory Bowel Disease
Celiac Disease
Liver Disease
Others
Macroenzymemia
Systemic Conditions Associated with Hyperenzymemia
Familial Aggregation and Genetics
Drug‐induced Hyperenzymemia
Extrapancreatic Abnormalities in Patients with Hyperenzymemia. Salivary Gland Diseases
Renal Insufficiency
Hyperenzymemia and Cancers
Eating Disorders
Others
Benign Pancreatic Hyperenzymemia (Gullo Syndrome)
Clinical Features
Physiopathology
Algorithm for Management of CAPH (Figure 22.2) Clinical History and Laboratory Evaluation
Isolated Hyperamylasemia
Pancreatic Hyperamylasemia and/or Hyperlipasemia
Conclusions
References
23 Definition and Etiology of Chronic Pancreatitis: What is Relevant for Clinical Practice?
Definition of Key Terms and Concepts
Dysfunction
Disorder
Disease
Syndrome
Diagnosis
Differential Diagnosis
Risk Factor
Etiology
Biomarkers
Modern Western Medicine
Precision Medicine
Traditional Definitions of Chronic Pancreatitis
Mechanistic Definition of Chronic Pancreatitis
Progressive Model of CP
Risk Factors and Etiologies
Pathogenic Genetic Mutations
Genetic Risk Factors
Subtypes of Inflammatory Diseases of the Pancreas. Acute Pancreatitis
Recurrent Acute Pancreatitis
Hereditary Pancreatitis
Familial Pancreatitis
Tropical Pancreatitis
Mendelian Syndromes Involving the Pancreas
Complex Pancreatic Disorders
Minimal Change Chronic Pancreatitis
References
24 Epidemiology of Chronic Pancreatitis : An Infrequent Disease or an Infrequently Diagnosed Disease?
Why is Chronic Pancreatitis Epidemiology so Imprecise?
Epidemiology
Why are Reported Data on Incidence and Prevalence of Chronic Pancreatitis Discrepant?
General Characteristics of Patients with Chronic Pancreatitis
Mortality
Conclusion
References
25 Alcoholic Chronic Pancreatitis and the Impact of Alcohol and Smoking Cessation in Chronic Pancreatitis
Introduction
Epidemiology
Direct Cellular Effects of Alcohol on the Pancreas
Metabolism of Alcohol by the Pancreas
Effects of Ethanol on Pancreatic Acinar Cells
Effects of Ethanol on Pancreatic Stellate Cells
Effects of Ethanol on Pancreatic Duct Cells
Individual Susceptibility to Alcoholic Pancreatitis
Impact of Alcohol and Smoking Cessation
Summary
References
26 What is Relevant on Genetics in Chronic Pancreatitis for Clinical Practice? What Genes and When to Evaluate Them?
Introduction
How to Screen
Probability of Identifying Genetic Variants in CP Patients
Which Genes are Clinically Relevant?
Screening for Cystic Fibrosis Transmembrane Conductance Regulator Gene Variants
What to do When a Variant has been Identified?
Increased Risk for Pancreatic Cancer in Chronic Pancreatitis Patients
How can Genetic Association Studies Change our Clinical Practice?
References
27 Pancreas Divisum and Other Potential Obstructive Causes of Chronic Pancreatitis : When and How to Treat Them?
Introduction
Idiopathic Pancreatitis
Pancreas Divisum
Criterion 1: The Prevalence of PD Should be Greater in Pancreatitis than in the General Population (Figure 27.2)
Criterion 2: A Dilated Dorsal Duct System Should be Present if There is a Functionally Significant Obstruction
Criterion 3: Pathological Changes Should Develop only in the Dorsal Duct
Criterion 4: Drainage Procedures of the duct of Santorini Should Reduce the Frequency or Severity of Recurrent Attacks of Pancreatitis
Alternate Genetic Explanations for Pancreatitis and PD
Other Potential Obstructive Causes of Chronic Pancreatitis
(Pre)Neoplastic Causes. Anatomical Congenital Variations Affecting the Biliopancreatic Ductal System
Acquired Obstructive Conditions
Non‐neoplastic Causes. Periampullary Obstruction: Duodenal Diverticula and Other Causes of Periampullary Obstruction
Main Pancreatic Duct Stricture
Postsurgical Pancreatic Duct Stricture
Postsurgical Intestinal Obstruction
Pancreatic Sphincter of Oddi Dysfunction
Disclosures
References
28 What to do in Clinical Practice Before Defining a Chronic Pancreatitis as Idiopathic? A Practical Protocol
Introduction
Etiologies of Chronic Pancreatitis. Alcoholic Chronic Pancreatitis
Hypertriglyceridemia‐induced Chronic Pancreatitis
Hypercalcemia‐induced Chronic Pancreatitis
Autoimmune Chronic Pancreatitis
Genetic Risk Factors and Hereditary Chronic Pancreatitis
Rare Causes of Chronic Pancreatitis
How to Classify Chronic Pancreatitis as Idiopathic
Diagnostic Approach
Anamnestic Investigation and Physical Examination
Laboratory Chemistry
Basic Laboratory Tests
Specific Tests to Address the Underlying Etiology of CP
Genetic Testing
Imaging Techniques
Transabdominal Ultrasound
Endoscopic Ultrasound
Endoscopic Retrograde Cholangiopancreatography
Computed Tomography and Magnetic Resonance Imaging
Conclusion
References
29 Computed Tomography for the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice
Introduction
Conventional CT in the Evaluation of Chronic Pancreatitis
Chronic Calcifying Pancreatitis
Chronic Obstructive Pancreatitis
Groove Pancreatitis
Autoimmune Pancreatitis
Complications Associated with Chronic Pancreatitis
Advanced CT Techniques
CT Volumetry and Assessment of Pancreatic Attenuation
Dual‐energy or Spectral CT
Perfusion CT
Future Challenges in CT Imaging
Conclusion
References
30 Role of MRI and MRCP in the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice
Introduction
Diagnosis
Severity
Complications
Conclusion
References
31 Role of Endoscopic Ultrasound and Associated Methods (Elastography, Contrast Enhancement) in the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice
Introduction
EUS in the Diagnosis of Chronic Pancreatitis
Standard EUS for the Diagnosis of Chronic Pancreatitis
Advanced EUS for the Diagnosis of Chronic Pancreatitis
EUS plus Endoscopic Pancreatic Function Test
EUS‐guided Elastography and Contrast Enhancement
EUS‐guided Tissue Acquisition
EUS for the Evaluation of Complications of Chronic Pancreatitis
EUS for Evaluating the Presence of Pancreatic Exocrine Insufficiency
EUS for the Detection of Pancreatic Malignancy in Chronic Pancreatitis
EUS‐guided Tissue Acquisition
EUS‐guided Elastography and CEH‐EUS
Conclusions
References
32 Endoscopic Pancreatic Function Test for the Functional Diagnosis of Chronic Pancreatitis : Indications and Practical Protocol
Introduction
History of Pancreas Function Tests
Pancreas Function Tests
Endoscopic Pancreas Function Tests
Pancreatic Function Test Performance
Abridged ePFT
Concerns Regarding Pancreatic Function Tests
Indications for ePFT
Practical Protocol
Conclusions
References
33 Role of Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis : Which Tests and How Should they be Performed in Clinical Practice?
Introduction
Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis in Patients with Inconclusive Imaging Findings
How to Perform the Secretin–CCK (Cerulein) Test
How to Perform the Endoscopic Pancreatic Function Test
Evaluation of Pancreatic Function as Screening Test for Patients with Clinical Symptoms Suggestive of Chronic Pancreatitis
Use of Fecal Elastase Test in Clinical Practice
References
34 Follow‐up of Patients with Chronic Pancreatitis in Clinical Practice : How and What for?
Introduction
Pain
Mechanical Obstruction
Neurogenic
Pancreatic Enzyme Replacement Therapy
Antioxidants
Analgesics
Endoscopic Therapy
Surgery
Nutritional Deficiencies
Diabetes
Exocrine Insufficiency
Functional Tests. Direct Tests
Indirect tests
Fecal Elastase
Fecal Chymotrypsin
Breath Tests
Coefficient of Fat Absorption
Serum Trypsinogen
Management of EPI
Final Considerations
Conclusion
References
35 Quality of Life in Chronic Pancreatitis
Introduction
Assessment
What QOL Questionnaires Measure
Available Questionnaires
EORTC QLQ System
Short Form Questionnaires
PANQOLI
Factors Affecting QOL. Pain
Insomnia and Fatigue
Weight Loss
Pancreatic Exocrine Insufficiency
Psychological Factors
Other Factors
Treatment. Medical Treatment
Pancreatic Enzyme Replacement
Endoscopic and Extracorporeal Therapies
Surgery
Conclusions
References
36 Medical Treatment of Pain in Chronic Pancreatitis : Guidelines for Clinical Practice
Introduction
Pathogenesis of Pain
Medical Pain Management. Risk Factors
Enzymes and Antioxidants
Analgesics
Simple Analgesics
Adjuvant Analgesics
Opioids
Alternative Treatments
Personalized Treatment
Pharmacological Considerations
Conclusion
References
37 Endoscopic Treatment of Pain in Chronic Pancreatitis : Indications, Optimal Timing, and Technical Aspects
Introduction
Selecting the Right Patient for Endoscopic Therapy: Who and When?
Factors Predictive of Clinical Success
Optimal Timing and Treatment Choice
Treatment of Pancreatic Duct Stones
Extracorporeal Shock‐wave Lithotripsy. Technical Aspects
Effectiveness and Safety
Pancreatoscopy‐guided Lithotripsy. Technical Aspects
Effectiveness and Safety
Treatment of Pancreatic Duct Strictures
Technical Aspects
Effectiveness and Safety
EUS‐guided Pancreaticogastrostomy. Technical Aspects
Effectiveness and Safety
Celiac Plexus Block
Technical Aspects
Effectiveness and Safety
Summary
References
38 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Chronic Pancreatitis : A Practical Protocol
Concept of Pancreatic Exocrine Insufficiency
Pathophysiology
Clinical Manifestations
Diagnosis
Tests Evaluating Fat Digestion: Coefficient of Fat Absorption and Breath Test
Tests Evaluating Pancreatic Secretion: Secretin–CCK Test and Fecal Elastase Test
Nutritional Markers for the Diagnosis of PEI
Diagnosis in Clinical Practice
Treatment
Nutritional Therapy
Pancreatic Enzyme Replacement Therapy. When to Prescribe
Aims
Administration
Correct Starting Dose
Efficacy
Unsatisfactory Response
Prevention and Prognosis
References
39 Surgical Treatment of Pain in Chronic Pancreatitis : Indications, Optimal Timing and Technical Approaches
Introduction
Indications and Contraindications for Surgical Treatment
Diagnostic Work‐up
Optimal Timing
Clinical Considerations in Selecting the Surgical Approach
Technical Approaches
Drainage Procedures. Longitudinal Pancreaticojejunostomy (Partington–Rochelle or Puestow)
Combined Drainage and Resection Procedures. Duodenum‐preserving Pancreatic Head Resection with End‐to‐end Pancreaticojejunostomy (Beger)
Berne Modification of the Duodenum‐preserving Pancreatic Head Resection with End‐to‐end Pancreaticojejunostomy
Local Resection of the Pancreatic Head with Longitudinal Pancreaticojejunostomy (Frey)
The “Hamburg” Modification to the Frey Procedure
Resection Procedures. Pancreaticoduodenectomy (Whipple)
Distal Pancreatectomy (with or without Spleen Preservation)
Total Pancreatectomy (with or without Spleen Preservation)
Total Pancreatectomy with Islet Autotransplantation
Denervation Procedures. Celiac Plexus Block
Sympathectomy
Tips and Tricks for Surgical Interventions
Outcomes and Quality of Life after Surgery
Follow‐up
Conclusion
References
40 Management of Chronic Pancreatic Pseudocyst : When to Observe, When and How to Drain?
Introduction
Definition of Pseudocyst
When to Observe or Drain
Important Preprocedure Considerations
Procedural Technique: How to Drain
Conventional Transmural Drainage
EUS‐guided Drainage
Multistep Technique Using Plastic Stents. Step I: Access
Step II: Transmural Tract Dilation
Step III: Stent Placement
Single‐step Technique Using LAMS
Non‐electrocautery‐enhanced Delivery System
Electrocautery‐enhanced Delivery System
Special Considerations. Disconnected Pancreatic Duct Syndrome
Ductal Communication with Pseudocyst
Multiple Pseudocysts
Postprocedure Care
Adverse Events
Conclusions
References
41 Vascular Complications in Chronic Pancreatitis
Introduction
Arterial Complications
Arterial Pseudoaneurysm in Chronic Pancreatitis. Pathophysiology
Clinical Features
Investigations
Management
Nonsurgical Interventions
Surgical Intervention
Venous Complications
Splenic Vein Thrombosis in Chronic Pancreatitis. Pathophysiology
Clinical Features
Investigations
Management
Splenic Vein Thrombosis with Symptomatic Varices
Splenic Vein Thrombosis with Asymptomatic Varices
Splenoportal/Mesenteric Vein Thrombosis
Miscellaneous Venous Complications
References
42 Surgical Therapy of Local Complications of Chronic Pancreatitis: Indications, Technical Approaches, and Optimal Timing
The Role of the Surgeon in the Treatment of Local Complications in Chronic Pancreatitis
Pancreatic Duct Strictures
Indications
Surgical Therapy
Optimal Timing
Pancreatic Pseudocyst
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Vascular Complications
Pseudoaneurysms
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Extrahepatic Portal Hypertension
Indications
Surgical Therapy
Optimal Timing
Bile Duct Obstruction
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Duodenal Obstruction
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Pancreatic Cancer
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Pancreatic Ascites and Pleural Effusion
Indications
Technical Approaches
Surgical Therapy
Optimal Timing
Conclusions
Acknowledgment
References
43 Endoscopic Treatment of Complications of Chronic Pancreatitis other than Pseudocyst
Introduction
Pancreatic Calculi
Pancreatic Duct Strictures
Biliary Strictures
EUS‐guided Celiac Block
Pancreatic Duct Leaks
EUS‐guided Access to MPD
References
44 Autoimmune Pancreatitis: Definition, Clinical Presentation, and Classification
Definition and Classification
Clinical Presentation
Diagnosis
Serology
Histology
Imaging
Other Organ Involvement
Response to Steroid Treatment
Treatment
Glucocorticoids
Immunosuppressants
Outcome and Follow‐up in Patients with AIP
References
45 Diagnosis of Autoimmune Pancreatitis A Protocol for Clinical Practice
Introduction
Diagnostic Approach
Diffuse AIP (Level 1 Imaging: Typical)
Focal AIP (Level 2 Imaging: Indeterminate/Atypical Imaging)
References
46 Treatment and Follow‐up of Autoimmune Pancreatitis in Clinical Practice
Introduction
Clinical Characteristics. Type 1 AIP (Lymphoplasmacytic Sclerosing Pancreatitis)
Type 2 AIP (Idiopathic Duct‐centric Pancreatitis)
Serology
Pathology
Pancreatic Imaging
Autoimmune Pancreatitis Versus Pancreatic Cancer
Diagnosis
Definition of Treatment Outcomes
Remission
Recrudescence
Relapse
Principles of Management of AIP
Indications for Treatment
Induction of Remission
Steroid Regimen for Induction of Remission
Steroid‐sparing Agents
Adjuvant Therapy. Diabetes Mellitus
Obstructive Jaundice
Exocrine Insufficiency
Patient Follow‐up. Initial Follow‐up to Assess Response to Induction
How to Taper Steroids
Prevention of Relapse
Choice of Treatment for Prevention of Relapse
Treatment of Relapses
Monitoring of Medication Side Effects
Summary
References
47 CFTR‐associated Pancreatic Disease: Genotype–Phenotype Correlations and Impact of CFTR‐modifying Therapy
Introduction
CFTR Gene and Protein
CFTR Mutation Classes
Genotype–Phenotype Correlations in CF
Genotype–Phenotype Correlations in Exocrine Pancreas Status in CF
Pancreatic Insufficiency Prevalence Score and Genotype–Phenotype Correlations in Pancreatitis in CF
The Pancreas in Cystic Fibrosis and CFTR‐related Disorders
Pathogenesis of CFTR‐related Pancreatitis
Pancreatic cystosis
CFTR‐modifying Therapies
Conclusion
References
48 Nutritional Therapy, Pancreatic Exocrine Insufficiency, and Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis: A Protocol for Clinical Practice
Introduction
Mechanisms of Pancreatic Exocrine Insufficiency
Diagnosis of Pancreatic Exocrine Insufficiency
Nutritional Consequences and Treatment of Pancreatic Exocrine Insufficiency
Follow‐up Care of Patients with Pancreatic Exocrine Insufficiency
Future of CF Nutrition Care
References
49 Epidemiological Impact of Pancreatic Cancer
Current Burden of Pancreatic Cancer
Time Trends
Risk Factors for Pancreatic Cancer
Heritability
Other Risk Factors
Attributable Fraction of Pancreatic Cancer due to Potentially Modifiable Risk Factors
Future Burden of Pancreatic Cancer
Conclusion
References
50 Molecular and Genetic Basis of Pancreatic Carcinogenesis: Which Concepts are Clinically Relevant?
Introduction
Individual Therapy Based on the Genomic and Transcriptomic Traits of Pancreatic Cancer
Organoids for Response Prediction
Enhancing the Activation of Immune Surveillance and Inhibition of Immune Suppression
Exploiting the Metabolic Alterations in Pancreatic Cancer Cells
Targeting the Tumor Stroma
Summary
References
51 New‐onset Diabetes as a Harbinger of Pancreatic Cancer: is Early Diagnosis Possible?
Introduction
Epidemiology of DM in PDAC. Dual Causality of DM and PDAC
Evidence for NOD being a Paraneoplastic Process
Using NOD for Early Detection of PDAC. The Need for Early Detection of PDAC to Improve Overall Survival
Why NOD is the Leading Candidate for Early Detection
Challenges and Opportunities of Studying NOD: Finding the High‐risk Cohort
Methods to Enrich the NOD Cohort to Screen for PDAC. The Role of T3cD and the Significance of New‐onset T3cD
Statistical Modeling Using Clinical and Algorithmic Identification
Biomarkers of T3cD and PDAC‐DM. T3cD Biomarker
PDAC‐DM Biomarkers
Current Research Endeavors. The CPDPC NOD Study
The Cancer Research UK‐funded UK Early Detection Initiative Study
The CPDPC DETECT Study
Commonalities of the Investigative Approaches in the United States and the UK
Challenges of Studying NOD Secondary to PDAC
Conclusions and Recommendations to Practitioners
Acknowledgments
References
52 Pancreatic Cancer Screening: Target Populations, Methods, and Protocols for Clinical Practice
Introduction
Target Populations
Germline Genetic Mutations Associated with Pancreatic Cancer
Peutz–Jeghers Syndrome
Hereditary Pancreatitis
Familial Atypical Multiple Mole Melanoma
Hereditary Breast and Ovarian Cancer
Lynch Syndrome
Ataxia Telangiectasia
Familial Pancreatic Cancer Families
Screening Modality. Imaging
Biomarkers
Screening Protocol. Who Should be Screened and When?
How Should you Screen?
Outcomes of Screening and Surveillance Programs
Cost‐effectiveness of Pancreatic Cancer Screening Programs
Conclusion
Acknowledgments
References
53 Clinical Usefulness of Biological Markers in Pancreatic Cancer
Introduction
Challenges in Early Detection of Pancreatic Cancer
Role of Clinically Established Biomarkers of Pancreatic Cancer
Early Cancer Detection by Novel Biomarkers. Metabolomics
Circulating Tumor Cells
Cell‐free DNA
Cell‐free MicroRNA
Exosomes
Summary
References
54 Staging Classification and Stratification of Pancreatic Cancer for Clinical Practice
Introduction
Clinical Staging
Additional Prognostic Factors
Clinically Relevant Molecular Features
Imaging Classification of Non‐metastatic Disease
Imaging for Staging. Computed Tomography
Magnetic Resonance Imaging
Positron Emission Tomography
Endoscopic Ultrasound
Suggested Radiology Report Format
Evaluating Response to Neoadjuvant Therapy. Clinical Evaluation
Pathological Evaluation
Future Directions
Acknowledgments
References
55 Imaging Diagnosis and Staging of Pancreatic Cancer: Which Methods are Essential and What Information Should they Provide?
Introduction
CT Technique
Anatomy
Pancreatic Adenocarcinoma. Tumor Detection
Initial Staging
Local Invasion
Metastatic Disease
Postsurgical Imaging
Normal Postsurgical Appearance
Postsurgical Complications
Recurrent and Metastatic Disease
Conclusion
References
56 The Role of Endoscopic Ultrasound and Associated Methods (Elastography, Contrast Enhancement) in the Diagnosis and Assessment of Resectability of Pancreatic Cancer
Introduction
Endoscopic Ultrasound for the Diagnosis and Staging of Pancreatic Cancer
Classification of Pancreatic Cancer According to EUS Findings
Role of EUS in the Diagnosis of Pancreatic Cancer
Accuracy of EUS Compared to Cross‐sectional Imaging Techniques for the Assessment of Locoregional Extension of Pancreatic Cancer. Accuracy for T and N Staging
Evaluation of Vascular Involvement
Nodal Invasion
EUS‐guided Fine Needle Biopsy
EUS Elastography. Theory and Technical Aspects of Elastography
Role of EUS Elastography in the Diagnosis of Pancreatic Cancer
Contrast‐enhanced EUS. General Considerations
Commercially Available Ultrasound Contrast Agents in Europe
Role of Contrast‐enhanced EUS in the Diagnosis of Pancreatic Cancer
Conclusion
References
57 EUS‐Guided FNA/FNB for Pancreatic Solid Lesions: When is it Indicated and What is the Optimal Technical Approach?
Introduction
Indications for Performing EUS‐guided Tissue Acquisition
Optimal Technical Approach to EUS Tissue Acquisition
General Rules for Performing EUS‐TA
EUS‐guided Fine Needle Aspiration
Number of Passes
Needle Size
Use of Suction
Use of the Stylet
EUS‐guided Fine Needle Biopsy
Conclusions
Acknowledgment
References
58 Surgical Treatment of Resectable Pancreatic Cancer: What is the Optimal Strategy?
Introduction
Standard Resections and Lymphadenectomy for Resectable Pancreatic Cancer
Pancreaticoduodenectomy (Kausch–Whipple Procedure)
Pancreatic Left Resection
Minimally Invasive Surgery
Extended Resections
Future Perspectives
References
59 Complications After Pancreatic Surgery: How to Deal with Them?
Introduction
Postoperative Pancreatic Fistula. Definition and Classification
Incidence and Risk Factors
Mitigation Strategies and Treatment
Post‐pancreatectomy Hemorrhage
Delayed Gastric Emptying
Biliary Leakage
Chyle Leak
Enhanced Recovery After Surgery Policies and Centralization
Conclusion
References
60 Neoadjuvant Treatment of Pancreatic Cancer : When and How?
Background
What we have Learnt about Pancreatic Cancer from Adjuvant Therapy Trials
The Relevance of a Positive Resection Margin, Local Recurrence and Overall Survival
Neoadjuvant Therapy. Rationale for Neoadjuvant Chemotherapy
Resectable Pancreatic Cancer
Borderline Resectable and Locally Advanced Pancreatic Cancer
Guidelines for Neoadjuvant Therapy
Classification of Resectability
Neoadjuvant Trials in Resectable and Borderline Resectable Pancreatic Cancer
Neoadjuvant Trials in Borderline Resectable Pancreatic Cancer
Neoadjuvant Trials in Resectable and Borderline Pancreatic Cancer
Neoadjuvant Treatment for Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer
Surgical Approaches Following Neoadjuvant Treatment for Borderline and Unresectable Locally Advanced Pancreatic Cancer
Conclusions
References
61 Adjuvant Therapy in Pancreatic Cancer : Options, Safety, and Outcomes
Introduction
Brief History and Development of Adjuvant Therapy
Recent Phase III Trials Evaluating Combination Chemotherapy
Current Standards and Choices in Adjuvant Therapy
Future Perspectives
Summary
References
62 Management of Pain in Pancreatic Cancer : An Algorithm for Clinical Routine
Relevance of Abdominal Pain in Pancreatic Cancer
Approach to Pain Management in Pancreatic Cancer
Pain Assessment
What is the Most Likely Cause of Pain?
Cancer Treatment
Psychological Support
Nutritional Management and Treatment of Pancreatic Exocrine Insufficiency
Pain Therapy in Pancreatic Cancer
Pharmacological Therapy
Interventional Neurolytic Methods
Other Therapies
Management of Pain in Pancreatic Cancer: An Algorithm for Clinical Routine
References
63 EUS‐guided Celiac Plexus Neurolysis for Pain in Pancreatic Cancer : When and How?
Introduction
When EUS‐CPN Should be Considered
Safety of EUS‐CPN
Celiac Ganglia Neurolysis
How to Inject and What to Expect: Unilateral vs. Bilateral Injection
Is the Future of EUS‐CPN Neurolysis with a Different Neurolytic?
Summary
References
64 The Role of Endoscopy in the Management of Unresectable Pancreatic Cancer
Background
Malignant Biliary Obstruction
Newer Advances in Endoscopic Palliation of Biliary Obstruction. Intraductal Radiofrequency Ablation
EUS‐guided Biliary Access and Drainage
Gastroduodenal Outlet Obstruction
EUS‐guided Gastrojejunostomy
Tumor‐related Bleeding
The Future
Conclusions
References
65 Chemotherapy for Nonresectable Pancreatic Cancer
Introduction
First Line
Single‐agent Chemotherapy
Gemcitabine
Oral Fluoropyrimidines: Capecitabine and S‐1
Fluorouracil‐based Combination Regimens
Gemcitabine Combinations
Gemcitabine plus Nab‐paclitaxel
Gemcitabine plus Capecitabine or S‐1
Gemcitabine plus Erlotinib and Other Molecularly Targeted Agents
Second Line
After First‐line Gemcitabine
Liposomal Irinotecan (MM‐398, Onivyde)
Irinotecan
Oxaliplatin‐based Regimens
Other Oxaliplatin‐based Regimens
Other Regimens
After First‐line FOLFIRINOX
Genetic Testing
Deficient Mismatch Repair/High Level of Microsatellite Instability
BRCA Mutation Carriers
Conclusions
References
66 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Pancreatic Cancer
Mechanisms of Pancreatic Exocrine Insufficiency in Pancreatic Cancer
PEI in Irresectable Pancreatic Cancer
PEI in Resectable Pancreatic Cancer
Symptoms of PEI
Diagnosis of PEI in Pancreatic Cancer
Treatment of PEI with PERT
Treatment Dosing
Gastric Barrier: pH and Gastric Emptying
PERT in Pancreatic Cancer
PERT in Unresectable Pancreatic Cancer
PERT in Resectable Pancreatic Cancer
Overall Survival and Quality of Life Benefit of PERT in Pancreatic Cancer
Undertreatment of PEI
Key Recommendations
References
67 Nutrition and Pancreatic Cancer
Introduction
Impact of Pancreatic Ductal Adenocarcinoma on Nutrient Metabolism
Pancreatic Exocrine Insufficiency
Cancer Cachexia and PDAC
Treatment Strategies for Malnutrition in Pancreatic Cancer
Locally Advanced and/or Metastatic Disease
Resectable Pancreatic Cancer. Preoperative Considerations
Postoperative Nutritional Support
Post‐discharge Nutrition
Survivorship
Conclusion
References
68 Present and Future of Local Therapies for Unresectable Pancreatic Cancer
Introduction
Direct Antitumor Therapy. EUS‐guided Radiofrequency Ablation
EUS‐guided Irreversible Electroporation
EUS‐guided Nd:YAG Laser Ablation
EUS‐guided Photodynamic Therapy
EUS‐guided High‐intensity Focused Ultrasound
EUS‐guided HybridTherm Ablation
Indirect Antitumor Therapy. EUS‐guided Fiducial Placement
EUS‐guided Brachytherapy
EUS‐guided Fine‐needle Antitumor Injection
Future Directions
References
69 New Pharmacological Approaches for Pancreatic Cancer Therapy : A Light at the End of the Tunnel?
Introduction
Pancreatic Cancer: Challenges in the Field. Tumor Heterogeneity
Desmoplasia in the Tumor
Late Detection of Disease
Surgical Challenges
Overcoming Challenges: Therapy against Pancreatic Cancer. Targeting EGF
Targeting Heat‐shock Proteins
Antistromal Therapy
Immunotherapy
Metabolic Inhibitors
Conclusion
Acknowledgments
Disclosures
References
70 Histological Classification of Pancreatic Cystic Neoplasms
Introduction
Serous Cystic Neoplasm
Mucinous Cystic Neoplasm
Intraductal Papillary Mucinous Neoplasm
Intraductal Oncocytic Papillary Neoplasm
Intraductal Tubulopapillary Neoplasm
Solid Pseudopapillary Neoplasm
References
71 Role of Endoscopic Ultrasound and Endoscopic Ultrasound‐associated Techniques in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Tumors
Introduction
EUS Imaging
EUS‐FNA
Cytology
Cyst Fluid Analysis
Molecular Biomarkers
EUS‐guided Through‐the‐needle Imaging
Cystoscopy
Needle‐based Confocal Laser Endomicroscopy
EUS‐guided Through‐the‐needle Biopsy
Summary
References
72 The Role of Multidetector CT, MRI and MRCP in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Neoplasms
Introduction
CT Technique
MRI Technique
Cystic Pancreatic Masses
Mucinous Cystic Neoplasms
Serous Cystadenomas
Intraductal Papillary Mucinous Neoplasms
Other Cystic Pancreatic Lesions. Solid Pseudopapillary Tumor
Lymphoepithelial Cysts
Neuroendocrine Tumors
Conclusion
References
73 Intraductal Papillary Mucinous Neoplasm : When to Observe, When to Operate, and Optimal Surgical Approach
Introduction
Clinical Considerations
Clinical History
Radiographic Features
Pancreatic Cyst Fluid Analysis
IPMN Guidelines. International Association of Pancreatology Sendai Guidelines
American Gastroenterological Association Guidelines
European Evidence‐based Guidelines
Reconciling the Differences
Surveillance Strategy for IPMNS not Meeting Criteria for Resection
Optimal Surgical Approach
Long‐term Follow‐up after Surgical Resection
Conclusions
References
74 Cystic Tumors Other than IPMN : When to Observe, When to Operate, and Optimal Surgical Approach
Introduction
Scope of Pancreatic Cystic Neoplasia
Mucinous Cystic Neoplasm
Indications for Surgery
Approach to Management
Serous Cystic Neoplasm
Indications for Surgery
Approach to Management
Solid Pseudopapillary Neoplasm
Indications for Surgery
Approach to Management
Cystic Pancreatic Endocrine Neoplasm
Indication for Surgery
Approach to Management
Other Rare Cystic Neoplasms. Lymphoepithelial Cysts
Cystic Lymphangioma
Cystic Degeneration of Solid Tumors
References
75 Pancreatic Cystic Tumors: any Role for Local Therapies?
Introduction
Indications for EUS‐guided Ablation Therapy
Cystic Pancreatic Tumors
EUS‐guided Therapy
Radiofrequency Ablation
Alcohol and/or Chemical Ablation
Conclusions
References
76 Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors : How to Deal with them in Clinical Practice?
Introduction
Clinical Presentation
Diagnosis. Laboratory
Imaging
Morphological Imaging
Functional Imaging
Staging Systems
Treatment
F‐PanNENs
Nonfunctioning PanNENs. Localized Disease
Metastatic Disease
Somatostatin analogs
Targeted Therapy
Chemotherapy
Peptide Receptor Radionuclide Therapy
Surgery
Acknowledgments
References
77 Other less Frequent Pancreatic Tumors : What Should be Known about Clinical Features, Diagnosis and Treatment?
Acinar Cell Carcinoma of Pancreas. Definition and Epidemiology
Clinical Symptoms
Diagnosis. Laboratory
Radiology
Fine‐needle Aspiration
Treatment
Hepatoid Carcinoma of Pancreas
Schwannoma of Pancreas
Perivascular Epithelial Cell Tumor of Pancreas
Hematological Malignancies of Pancreas
Non‐Hodgkin Lymphoma of the Pancreas
Post‐transplantation Lymphoproliferative Disorder
Granulocytic Sarcoma
Multiple Myeloma and Solitary Plasmacytoma
Castleman Disease
Primary Leiomyoma of Pancreas
Primary Leiomyosarcoma of Pancreas
Pancreatic Lipoma
Pancreatic Liposarcoma
Cystic Lymphangioma of Pancreas
Squamous‐lined Cyst of Pancreas
Lymphoepithelial Cyst
Epidermoid Cyst
Dermoid Cyst or Mature Cystic Teratoma
Solid Papillary Neoplasm
Adult Pancreatoblastoma
Pancreatic Metastasis from Other Tumors
Renal Cell Cancer Metastasis
Colorectal Cancer Metastasis
Melanoma Metastasis
Breast Cancer Metastasis
Lung Cancer Metastasis
Sarcoma Metastasis
References
78 Diagnosis and Therapy of Exocrine Pancreatic Insufficiency after Gastric and Pancreatic Surgery
Introduction
Gastrectomy. Pathophysiology of EPI
How to Assess Pancreatic Function in Gastrectomized Patients
Pancreatic Enzyme Replacement Therapy after Gastric Resection
Well‐being of Gastrectomized Patients with Maldigestion
Future Perspectives
Pancreatectomy. Pathophysiology of EPI
How to Assess Pancreatic Function in Pancreatic‐resected Patients
Pancreatic Enzyme Replacement Therapy after Pancreatic Resection
Well‐being of Pancreatic‐resected Patients with Maldigestion
Pancreatic Neoplasm
Chronic Pancreatitis
Type of Surgery and Reconstruction
Future Perspectives
References
79 Pancreatic Exocrine Insufficiency in Type 1 and Type 2 Diabetes Mellitus : Lessons from Pancreatologists to Diabetologists
Historical Aspects of Pancreatic Diseases and Diabetes Mellitus [1,2]
Pancreatic Exocrine Function in Patients with Diabetes Mellitus
Pancreas Morphology in Patients with Diabetes Mellitus
Pathophysiological Concepts of Altered Exocrine Pancreas Morphology and Function in Type 1 and Type 2 Diabetes Mellitus
Exocrine Pancreatic Pathology as a Consequence of Diabetes Mellitus. Exocrine Changes in Type 1 Diabetes Mellitus
Exocrine Changes in Type 2 Diabetes Mellitus
Exocrine and Endocrine Pathology Caused by one Underlying Disease Process
Clinical Impact of Exocrine Disease in Type 1 and Type 2 Diabetes Mellitus
Conclusion
References
80 Diabetes Mellitus Related to Diseases of the Exocrine Pancreas (Pancreatogenic Diabetes) : Diagnosis and Treatment
Introduction
Epidemiology
Chronic Pancreatitis‐related Diabetes Mellitus
Post‐pancreatectomy Diabetes Mellitus
Acute Pancreatitis‐related Diabetes Mellitus
Cystic Fibrosis‐related Diabetes Mellitus
Diagnosis
Treatment
Chronic Pancreatitis‐related Diabetes Mellitus
Acute Pancreatitis‐related Diabetes Mellitus
Pancreatic Ductal Adenocarcinoma‐related Diabetes Mellitus
Cystic Fibrosis‐related Diabetes
Knowledge Gaps
Conclusions
Acknowledgments
References
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