Clinical
Pancreatology for Practising Gastroenterologists and Surgeons
Second Edition
Edited by
J. Enrique Domínguez-Muñoz MD, PhD
Director, Department of Gastroenterology and Hepatology
University Hospital of Santiago de Compostela Santiago de Compostela, Spain
This edition first published 2021 © 2021 John Wiley & Sons Ltd
Edition History
Blackwell Publishing Ltd (1e, 2005)
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Library of Congress Cataloging-in-Publication Data
Names: Domínguez-Muñoz , J. Enrique, editor.
Title: Clinical pancreatology for practising gastroenterologists and surgeons / edited by J. Enrique Domínguez-Muñoz.
Description: Second edition. | Hoboken, NJ : Wiley-Blackwell, 2021. | Includes bibliographical references and index.
Identifiers: LCCN 2020025990 (print) | LCCN 2020025991 (ebook) | ISBN 9781119570073 (cloth) | ISBN 9781119570080 (adobe pdf) | ISBN 9781119570141 (epub)
Subjects: MESH: Pancreatitis–diagnosis | Pancreatitis–therapy | Gastroenterology–methods
Classification: LCC RC858.P35 (print) | LCC RC858.P35 (ebook) | NLM WI 805 | DDC 616.3/7–dc23
LC record available at https://lccn.loc.gov/2020025990
LC ebook record available at https://lccn.loc.gov/2020025991
Cover Design: Wiley
Cover Images: J. Enrique Domínguez-Muñoz
Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India 10 9 8 7 6 5 4 3 2 1
Contents
Contributors xxxiii
Foreword xlvi
Preface xlvii
Dedication xlviii
Section I Acute Pancreatitis 1
1 Acute Pancreatitis: An Overview 3
Jodie A . Barkin and Jamie S. Barkin
Introduction 3
Causes 3
Laboratory Diagnosis 6
Imaging 6
Risk Stratification 7
Classification 7
Treatment 8
Prophylactic Antibiotics 8
Nutrition 9
Post-discharge Cholecystectomy 9
Long-term Sequelae 11
References 12
2 How to Deal with the Etiological Diagnosis of Acute Pancreatitis in Clinical Practice? 17
Soumya Jagannath and Pramod Kumar Garg
Introduction 17
Etiological Diagnosis 17
Gallstone-induced Pancreatitis 17
Microlithiasis 18
Alcoholic Pancreatitis 19
Drug-induced Pancreatitis 19
Other Etiological Diagnoses of Acute Pancreatitis 19
Hypercalcemia 19
Hypertriglyceridemia 19
Smoking 19
Type 2 Diabetes Mellitus 19
Pancreatobiliary Tumors 20
Post-ERCP Pancreatitis 20
Single and Double Balloon Enteroscopy 20
Congenital Anomalies 20
Idiopathic Acute Pancreatitis 21
v
Investigative Work-up 21
Concluding Remarks 22
References 22
3 Definition of Complications and Severity of Acute Pancreatitis for Clinical Practice 25
David X. Jin, Peter A. Banks, and Julia McNabb-Baltar
Background 25
The Atlanta Classification 1992 25
The Revised Atlanta Classification 2012 25
Definition of Organ Failure and Complications in Acute Pancreatitis 25
Organ Failure 25
Local Complications 26
Systemic Complications 27
Definition of Severity in Acute Pancreatitis 27
Mild Acute Pancreatitis 28
Moderately Severe Acute Pancreatitis 28
Severe Acute Pancreatitis 28
Limitations of the Revised Atlanta Classification 28
The Determinant-Based Classification 28
Conclusion 29
References 29
4 Early Prediction of Severity in Acute Pancreatitis: What can be Done in Clinical Practice? 31
Peter J. Lee and Georgios I. Papachristou
Introduction 31
Available Prediction Tools 31
Volume Deficit 31
Inflammatory Response 33
Host-related Characteristics 33
Age and Comorbidity Burden 33
Obesity and Hypertriglyceridemia 33
Degree of Parenchymal and Extra-parenchymal Injury 34
Scoring Systems 34
Limitations and Future of Current Scoring Systems and Predictive Markers 35
Artificial Intelligence and Biomarkers: the Future? 35
References 36
5 Role of CT Scan in Acute Pancreatitis: When is it Indicated and What Information can be Obtained? 40
Elham Afghani, Mahya Faghih, and Vikesh K. Singh
CT Imaging in Acute Pancreatitis 40
Confirming the Diagnosis of AP 40
Assessing the Etiology of Acute Pancreatitis 40
Assessing the Prognosis of Acute Pancreatitis 41
Identifying Local Complications Associated with Acute Pancreatitis 41
Pancreatic Necrosis and Peripancreatic Fluid Collections 41
Vascular Complications 42
Other Complications 43
Timing of CT in Acute Pancreatitis 43
Limitations of CT Imaging 44
Conclusion 44
Disclosures 44
References 44
Contents vi
6 Role of MRI in Acute Pancreatitis: When is it Indicated and What Information can be Obtained? 47
Fatih Akisik
Introduction 47
MRI and MRCP Protocol for Pancreas Examination 47
Interstitial Edematous Pancreatitis 48
Necrotizing Pancreatitis 48
Complications of Acute Pancreatitis 50
Fluid Collections 50
Acute Peripancreatic Fluid Collection 50
Acute Necrotic Collection 50
Pseudocyst 50
Walled-off Necrosis 50
Vascular Complications 50
References 51
7 Treatment of Acute Pancreatitis in The Emergency Room: What Should be Done
During the First Hours of Disease? 53
Thiruvengadam Muniraj and Santhi Swaroop Vege
Introduction 53
Early Diagnosis in the Emergency Room 53
Initial Work-up for Etiology 54
Severity Assessment, Triage, and Disposition 54
Specialty Consultation 54
Management 55
First-line Medical Management: Fluid Resuscitation 55
Type of Intravenous Fluid to Administer 55
Antibiotics 55
Pain Control 55
Nutrition 56
Summary 56
References 56
8 Acute Pancreatitis: A Practical Guideline for the Monitoring and Treatment of Systemic Complications 59
Enrique de Madaria and Felix Zubia-Olaskoaga
Introduction 59
Acute Pancreatitis and Systemic Complications: Definitions, Importance, and Incidence 59
Monitoring Respiratory Function and Management of Respiratory Failure 60
Shock: Volume Management and Hemodynamic Monitoring 60
Acute Renal Failure: Early Detection and Management 61
Other Systemic Complications Associated with Acute Pancreatitis 62
Hypocalcemia 62
Disseminated Intravascular Coagulation 62
Gastrointestinal Bleeding 62
Pancreatic Encephalopathy and Posterior Reversible Encephalopathy Syndrome 62
Abdominal Compartment Syndrome 63
References 63
9 Guidelines for the Treatment of Pain in Acute Pancreatitis 66
László Czakó
Introduction 66
Nonsteroidal Anti-inflammatory Drugs 66
Opioid Analgesics 67
Epidural Analgesia 68
Contents vii
Local Anesthetics 69
Summary 70
References 70
10 Nutrition in the Acute Phase of Pancreatitis: Why, When, How and How Long? 72
Angela Pham and Chris E. Forsmark
Why 72
When 73
How 73
What to Feed 75
References 75
11 Oral Refeeding in Acute Pancreatitis: When and How Should it be Restarted? 78
José Lariño-Noia and Daniel de la Iglesia-García
Introduction 78
What is the Optimal Timing of Refeeding in AP? 78
How Should Oral Refeeding be Scheduled? 79
What are the Predictors of Oral Feeding Intolerance in AP Patients? 79
Summary and Recommendations 81
References 81
12 Pharmacological Therapy for Acute Pancreatitis: Any Light at the End of the Tunnel? 83
Rajarshi Mukherjee, Muhammad Awais, Wenhao Cai, Wei Huang, Peter Szatmary, and Robert Sutton
Introduction 83
Calcium Toxicity 84
Mitochondrial Dysfunction 84
Autophagy 86
Acinar Cell Secretion, Serine Proteases, and Serine Protein Kinases 86
Immune Cells/Inflammation 87
CFTR 89
Design of Future Clinical Trials 89
Conclusion 89
References 90
13 Indication and Optimal Timing of ERCP in Acute Pancreatitis 95
Theodor Voiosu, Ivo Boškoski, and Guido Costamagna
Introduction 95
ERCP in the Setting of Acute Biliary Pancreatitis 95
Urgent ERCP 96
Elective ERCP 96
Additional Applications of ERCP in the Setting of Acute Pancreatitis 97
Conclusions 98
Disclosures 98
References 98
14 How to Deal with Infected Pancreatic Necrosis? 100
J. Enrique Domínguez-Muñoz
Introduction 100
Prevention of Infection of (Peri)pancreatic Necrosis 100
Diagnosis of Infected (Peri)pancreatic Necrosis 101
How to Deal with Infected (Peri)pancreatic Necrosis 101
Systemic Antibiotics 101
Endoscopic or Percutaneous Drainage 101
Contents viii
Endoscopic or Laparoscopic Necrosectomy 102
References 102
15 Minimally Invasive Surgical Necrosectomy in Clinical Practice:
Indications, Technical Issues, and Optimal Timing 105
Patricia Sánchez-Velázquez, Fernando Burdío, and Ignasi Poves†
Introduction 105
Percutaneous Drainage 105
Sinus Tract Endoscopy 106
Endoscopic (Endoluminal) Approach 106
Retroperitoneal Approach 108
Laparoscopic Transperitoneal Approach 109
References 111
16 Endoscopic Necrosectomy in Clinical Practice: Indications, Technical Issues and Optimal Timing 113
Jodie A . Barkin and Andres Gelrud
Introduction 113
Management of Symptomatic Pseudocysts 114
Management of Symptomatic Walled-off Necrosis 114
Indications and Timing for Intervention 114
Choosing the Best Interventional Option: the Step-up Approach 115
Methods of Endoscopic Necrosectomy and Stent Choice 116
Conclusion 117
References 118
17 Management of Acute Pancreatic Pseudocyst: When to Observe, When and How to Drain? 120
Muhammad F. Dawwas and Kofi W. Oppong
Introduction 120
Evaluation 120
Drainage Therapy 122
Disconnected Pancreatic Duct Syndrome 124
Complications 124
Conclusion 124
References 125
18 The Disconnected Main Pancreatic Duct Syndrome: How to Proceed in Clinical Practice? 126
Mario Peláez-Luna, Andrea Soriano-Ríos, and Luis Uscanga-Dominguez
Introduction 126
Epidemiology 126
Risk Factors and Predictors of DPDS 126
Clinical Significance 126
Clinical Presentation 127
Diagnosis 127
Treatment 128
Conclusions 129
References 130
19 Vasculature Complications in Pancreatitis: How to Deal with Them? 132
Daniel G. McCall and Timothy B. Gardner
Venous Complications 132
Splanchnic Thrombosis Rates 132
Risk Factors for Thrombosis 132
Clinical Findings 133
Contents ix
Screening 133
Splenic Vein Thrombosis 133
Portal Vein Thrombosis 133
Management of Visceral Vein Thrombosis 134
Anticoagulation 134
Surgical Management 135
Miscellaneous Venous Complications 135
Bowel Wall Ischemia 135
Portal Vein–Pseudocyst Fistula 135
Arterial Complications 135
Pseudoaneurysm 135
Pseudoaneurysm and Risk of Rupture 136
Hemosuccus Pancreaticus 137
Imaging of Pseudoaneurysm or Potential Hemorrhage 137
Ruptured Pseudoaneurysm Management 138
Summary 138
References 138
20 Acute Relapsing Pancreatitis: What can be Done to Prevent Relapses? 141
Jorge D. Machicado and Dhiraj Yadav
Introduction 141
Definition 141
Burden 141
Demographics 142
Etiology 142
Diagnostic Work-up 143
Natural History and Risk of Progression 144
Preventing Recurrences and Disease Progression 146
Conclusion 147
Acknowledgment 147
References 147
21 Diagnosis and Therapeutic Approach to Pancreatic Exocrine Insufficiency after Acute Pancreatitis 151
Hester C. Timmerhuis, Christa J. Sperna Weiland, and Hjalmar C. van Santvoort
Introduction 151
Symptoms 151
Diagnosis 152
Management 152
Summary 154
References 155
22 Asymptomatic Chronic Elevation of Serum Pancreatic Enzymes: How to Deal with It? 158
Giuseppe Vanella, Paolo Giorgio Arcidiacono, and Gabriele Capurso
Introduction 158
Physiology of Pancreatic Enzymes 158
Pancreatic Abnormalities in Patients with Pancreatic Hyperenzymemia 158
Pancreatic Hyperenzymemia: A Clue to Malignancy? 160
Pancreatic Abnormalities at Second-level Imaging 160
Gastrointestinal Diseases and Pancreatic Hyperenzymemia 160
Inflammatory Bowel Disease 160
Celiac Disease 160
Liver Disease 161
Others 161
Contents x
Macroenzymemia 161
Systemic Conditions Associated with Hyperenzymemia 161
Familial Aggregation and Genetics 161
Drug-induced Hyperenzymemia 161
Extrapancreatic Abnormalities in Patients with Hyperenzymemia 162
Salivary Gland Diseases 162
Renal Insufficiency 162
Hyperenzymemia and Cancers 162
Eating Disorders 162
Others 162
Benign Pancreatic Hyperenzymemia (Gullo Syndrome) 163
Clinical Features 163
Physiopathology 163
Algorithm for Management of CAPH (Figure 22.2) 163
Clinical History and Laboratory Evaluation 163
Isolated Hyperamylasemia 164
Pancreatic Hyperamylasemia and/or Hyperlipasemia 165
Conclusions 165
References 165
Section II Chronic Pancreatitis 169
23 Definition and Etiology of Chronic Pancreatitis: What is Relevant for Clinical Practice? 171
David C. Whitcomb
Definition of Key Terms and Concepts 171
Dysfunction 171
Disorder 171
Disease 171
Syndrome 172
Diagnosis 172
Differential Diagnosis 172
Risk Factor 172
Etiology 172
Biomarkers 172
Modern Western Medicine 174
Precision Medicine 174
Traditional Definitions of Chronic Pancreatitis 174
Mechanistic Definition of Chronic Pancreatitis 174
Progressive Model of CP 175
Risk Factors and Etiologies 175
Pathogenic Genetic Mutations 176
Genetic Risk Factors 176
Subtypes of Inflammatory Diseases of the Pancreas 176
Acute Pancreatitis 176
Recurrent Acute Pancreatitis 177
Hereditary Pancreatitis 177
Familial Pancreatitis 177
Tropical Pancreatitis 177
Mendelian Syndromes Involving the Pancreas 177
Complex Pancreatic Disorders 177
Minimal Change Chronic Pancreatitis 177
References 177
Contents xi
24 Epidemiology of Chronic Pancreatitis: An Infrequent Disease or an Infrequently Diagnosed Disease? 180
Philippe Lévy and Vinciane Rebours
Why is Chronic Pancreatitis Epidemiology so Imprecise? 180
Epidemiology 181
Why are Reported Data on Incidence and Prevalence of Chronic Pancreatitis Discrepant? 182
General Characteristics of Patients with Chronic Pancreatitis 182
Mortality 182
Conclusion 183
References 183
25 Alcoholic Chronic Pancreatitis and the Impact of Alcohol and Smoking Cessation in Chronic Pancreatitis 185
Jeremy S. Wilson, Romano C. Pirola, and Minoti V. Apte
Introduction 185
Epidemiology 185
Direct Cellular Effects of Alcohol on the Pancreas 185
Metabolism of Alcohol by the Pancreas 185
Effects of Ethanol on Pancreatic Acinar Cells 186
Effects of Ethanol on Pancreatic Stellate Cells 187
Effects of Ethanol on Pancreatic Duct Cells 187
Individual Susceptibility to Alcoholic Pancreatitis 187
Impact of Alcohol and Smoking Cessation 188
Summary 189
References 189
26 What is Relevant on Genetics in Chronic Pancreatitis for Clinical Practice? What Genes and When to Evaluate Them? 193
Jonas Rosendahl
Introduction 193
How to Screen 193
Probability of Identifying Genetic Variants in CP Patients 193
Which Genes are Clinically Relevant? 193
Screening for Cystic Fibrosis Transmembrane Conductance Regulator Gene Variants 195
What to do When a Variant has been Identified? 195
Increased Risk for Pancreatic Cancer in Chronic Pancreatitis Patients 195
How can Genetic Association Studies Change our Clinical Practice? 196
References 196
27 Pancreas Divisum and Other Potential Obstructive Causes of Chronic Pancreatitis: When and How to Treat Them? 198
Matthew J. DiMagno and Erik-Jan Wamsteker
Introduction 198
Idiopathic Pancreatitis 198
Pancreas Divisum 199
Criterion 1: The Prevalence of PD Should be Greater in Pancreatitis than in the General Population 200
Criterion 2: A Dilated Dorsal Duct System Should be Present if There is a Functionally Significant Obstruction 200
Criterion 3: Pathological Changes Should Develop only in the Dorsal Duct 201
Criterion 4: Drainage Procedures of the duct of Santorini Should Reduce the Frequency or Severity of Recurrent Attacks of Pancreatitis 201
Alternate Genetic Explanations for Pancreatitis and PD 202
Other Potential Obstructive Causes of Chronic Pancreatitis 202
(Pre)Neoplastic Causes 202
Contents xii
Anatomical Congenital Variations Affecting the Biliopancreatic Ductal System 202
Acquired Obstructive Conditions 203
Non-neoplastic Causes 203
Periampullary Obstruction: Duodenal Diverticula and Other Causes of Periampullary Obstruction 203
Main Pancreatic Duct Stricture 204
Postsurgical Pancreatic Duct Stricture 204
Postsurgical Intestinal Obstruction 204
Pancreatic Sphincter of Oddi Dysfunction 204
Disclosures 204
References 204
28 What to do in Clinical Practice Before Defining a Chronic Pancreatitis as Idiopathic? A Practical Protocol 208
Felix Lämmerhirt, Frank Ulrich Weiss, and Markus M. Lerch
Introduction 208
Etiologies of Chronic Pancreatitis 208
Alcoholic Chronic Pancreatitis 208
Hypertriglyceridemia-induced Chronic Pancreatitis 209
Hypercalcemia-induced Chronic Pancreatitis 209
Autoimmune Chronic Pancreatitis 209
Genetic Risk Factors and Hereditary Chronic Pancreatitis 210
Rare Causes of Chronic Pancreatitis 210
How to Classify Chronic Pancreatitis as Idiopathic 210
Diagnostic Approach 210
Anamnestic Investigation and Physical Examination 211
Laboratory Chemistry 211
Basic Laboratory Tests 211
Specific Tests to Address the Underlying Etiology of CP 212
Genetic Testing 212
Imaging Techniques 212
Transabdominal Ultrasound 212
Endoscopic Ultrasound 213
Endoscopic Retrograde Cholangiopancreatography 214
Computed Tomography and Magnetic Resonance Imaging 214
Conclusion 214
References 215
29 Computed Tomography for the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice 218
Roberto García-Figueiras, Sandra Baleato-González, and Gonzalo Tardáguila de la Fuente
Introduction 218
Conventional CT in the Evaluation of Chronic Pancreatitis 218
Chronic Calcifying Pancreatitis 218
Chronic Obstructive Pancreatitis 219
Groove Pancreatitis 221
Autoimmune Pancreatitis 221
Complications Associated with Chronic Pancreatitis 221
Advanced CT Techniques 221
CT Volumetry and Assessment of Pancreatic Attenuation 221
Dual-energy or Spectral CT 222
Perfusion CT 222
Future Challenges in CT Imaging 223
Conclusion 224
References 224
Contents xiii
30 Role of MRI and MRCP in the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice 227
Jordan K. Swensson and Temel Tirkes
Introduction 227
Diagnosis 227
Severity 229
Complications 230
Conclusion 230
References 231
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 233
Julio Iglesias-Garcia
Introduction 233
EUS in the Diagnosis of Chronic Pancreatitis 233
Standard EUS for the Diagnosis of Chronic Pancreatitis 233
Advanced EUS for the Diagnosis of Chronic Pancreatitis 236
EUS plus Endoscopic Pancreatic Function Test 236
EUS-guided Elastography and Contrast Enhancement 237
EUS-guided Tissue Acquisition 237
EUS for the Evaluation of Complications of Chronic Pancreatitis 238
EUS for Evaluating the Presence of Pancreatic Exocrine Insufficiency 238
EUS for the Detection of Pancreatic Malignancy in Chronic Pancreatitis 239
EUS-guided Tissue Acquisition 239
EUS-guided Elastography and CEH-EUS 239
Conclusions 240
References 240
32 Endoscopic Pancreatic Function Test for the Functional Diagnosis of Chronic Pancreatitis: Indications and Practical Protocol 243
Luis F. Lara and Darwin L. Conwell
Introduction 243
History of Pancreas Function Tests 243
Pancreas Function Tests 244
Endoscopic Pancreas Function Tests 245
Pancreatic Function Test Performance 245
Abridged ePFT 246
Concerns Regarding Pancreatic Function Tests 246
Indications for ePFT 246
Practical Protocol 247
Conclusions 247
References 248
33 Role of Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis: Which Tests and How Should they be Performed in Clinical Practice? 250
J. Enrique Domínguez-Muñoz
Introduction 250
Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis in Patients with Inconclusive Imaging Findings 251
How to Perform the Secretin–CCK (Cerulein) Test 251
How to Perform the Endoscopic Pancreatic Function Test 252
Evaluation of Pancreatic Function as Screening Test for Patients with Clinical Symptoms Suggestive of Chronic Pancreatitis 252
Contents xiv
Use of Fecal Elastase Test in Clinical Practice 253
References 253
34 Follow-up of Patients with Chronic Pancreatitis in Clinical Practice: How and What for? 255
Antonio Mendoza-Ladd, Luis F. Lara, and Darwin L. Conwell
Introduction 255
Pain 255
Mechanical Obstruction 255
Neurogenic 255
Pancreatic Enzyme Replacement Therapy 255
Antioxidants 256
Analgesics 256
Endoscopic Therapy 256
Surgery 256
Nutritional Deficiencies 257
Diabetes 258
Exocrine Insufficiency 258
Functional Tests 258
Direct Tests 258
Indirect tests 258
Management of EPI 259
Final Considerations 259
Conclusion 260
References 260
35 Quality of Life in Chronic Pancreatitis 265
Colin D. Johnson
Introduction 265
Assessment 265
What QOL Questionnaires Measure 265
Available Questionnaires 266
EORTC QLQ System 266
Short Form Questionnaires 266
PANQOLI 267
Factors Affecting QOL 267
Pain 267
Insomnia and Fatigue 268
Weight Loss 268
Pancreatic Exocrine Insufficiency 268
Psychological Factors 268
Other Factors 269
Treatment 269
Medical Treatment 269
Pancreatic Enzyme Replacement 270
Endoscopic and Extracorporeal Therapies 270
Surgery 270
Conclusions 271
References 271
36 Medical Treatment of Pain in Chronic Pancreatitis: Guidelines for Clinical Practice 273
Asbjørn Mohr Drewes, Louise Kuhlman, Trine Andresen, and Søren Schou Olesen
Introduction 273
Pathogenesis of Pain 273
Contents xv
Medical Pain Management 274
Risk Factors 274
Enzymes and Antioxidants 274
Analgesics 275
Simple Analgesics 275
Adjuvant Analgesics 275
Opioids 277
Alternative Treatments 277
Personalized Treatment 278
Pharmacological Considerations 278
Conclusion 279
References 279
37 Endoscopic Treatment of Pain in Chronic Pancreatitis: Indications, Optimal Timing, and Technical Aspects 283
Pauline M. C. Stassen, Pieter J. F. de Jonge, Jan-Werner Poley, Djuna L. Cahen, and Marco .J. Bruno
Introduction 283
Selecting the Right Patient for Endoscopic Therapy: Who and When? 283
Factors Predictive of Clinical Success 283
Optimal Timing and Treatment Choice 284
Treatment of Pancreatic Duct Stones 284
Extracorporeal Shock-wave Lithotripsy 284
Technical Aspects 284
Effectiveness and Safety 285
Pancreatoscopy-guided Lithotripsy 285
Technical Aspects 285
Effectiveness and Safety 286
Treatment of Pancreatic Duct Strictures 286
Technical Aspects 286
Effectiveness and Safety 287
EUS-guided Pancreaticogastrostomy 287
Technical Aspects 287
Effectiveness and Safety 287
Celiac Plexus Block 288
Technical Aspects 288
Effectiveness and Safety 288
Summary 288
References 288
38 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Chronic Pancreatitis: A Practical Protocol 292
J. Enrique Domínguez-Muñoz
Concept of Pancreatic Exocrine Insufficiency 292
Pathophysiology 292
Clinical Manifestations 293
Diagnosis 293
Tests Evaluating Fat Digestion: Coefficient of Fat Absorption and Breath Test 294
Tests Evaluating Pancreatic Secretion: Secretin–CCK Test and Fecal Elastase Test 295
Nutritional Markers for the Diagnosis of PEI 295
Diagnosis in Clinical Practice 296
Treatment 296
Nutritional Therapy 296
Pancreatic Enzyme Replacement Therapy 297
When to Prescribe 297
Contents xvi
Aims 297
Administration 297
Correct Starting Dose 297
Efficacy 297
Unsatisfactory Response 297
Prevention and Prognosis 298
References 298
39 Surgical Treatment of Pain in Chronic Pancreatitis: Indications, Optimal Timing and Technical Approaches 301
Benjamin P.T. Loveday and John A. Windsor
Introduction 301
Indications and Contraindications for Surgical Treatment 301
Diagnostic Work-up 302
Optimal Timing 302
Clinical Considerations in Selecting the Surgical Approach 303
Technical Approaches 303
Drainage Procedures 303
Longitudinal Pancreaticojejunostomy (Partington–Rochelle or Puestow) 303
Combined Drainage and Resection Procedures 307
Duodenum-preserving Pancreatic Head Resection with End-to-end Pancreaticojejunostomy (Beger) 307
Berne Modification of the Duodenum-preserving Pancreatic Head Resection with End-to-end
Pancreaticojejunostomy 307
Local Resection of the Pancreatic Head with Longitudinal Pancreaticojejunostomy (Frey) 307
The “Hamburg” Modification to the Frey Procedure 307
Resection Procedures 307
Pancreaticoduodenectomy (Whipple) 307
Distal Pancreatectomy (with or without Spleen Preservation) 307
Total Pancreatectomy (with or without Spleen Preservation) 307
Total Pancreatectomy with Islet Autotransplantation 308
Denervation Procedures 308
Celiac Plexus Block 308
Sympathectomy 308
Tips and Tricks for Surgical Interventions 308
Outcomes and Quality of Life after Surgery 308
Follow-up 309
Conclusion 309
References 309
40 Management of Chronic Pancreatic Pseudocyst: When to Observe, When and How to Drain? 314
Shyam Varadarajulu
Introduction 314
Definition of Pseudocyst 314
When to Observe or Drain 314
Important Preprocedure Considerations 315
Procedural Technique: How to Drain 315
Conventional Transmural Drainage 315
EUS-guided Drainage 317
Multistep Technique Using Plastic Stents 317
Single-step Technique Using LAMS 317
Special Considerations 317
Disconnected Pancreatic Duct Syndrome 317
Ductal Communication with Pseudocyst 318
Multiple Pseudocysts 319
Contents xvii
Postprocedure Care 319
Adverse Events 319
Conclusions 320
References 320
41 Vascular Complications in Chronic Pancreatitis 322
Anil K. Agarwal, Raja Kalayarasan, and Amit Javed
Introduction 322
Arterial Complications 322
Arterial Pseudoaneurysm in Chronic Pancreatitis 322
Pathophysiology 322
Clinical Features 322 Investigations 323 Management 323
Venous Complications 327
Splenic Vein Thrombosis in Chronic Pancreatitis 327
Pathophysiology 327
Clinical Features 327 Investigations 327 Management 328
Splenoportal/Mesenteric Vein Thrombosis 329
Miscellaneous Venous Complications 331
References 331
42 Surgical Therapy of Local Complications of Chronic Pancreatitis: Indications, Technical Approaches, and Optimal Timing 333
Ricardo Arvizu Castillo, Elena Muñoz-Forner, and Luis Sabater
The Role of the Surgeon in the Treatment of Local Complications in Chronic Pancreatitis 333
Pancreatic Duct Strictures 334
Indications 334
Surgical Therapy 334
Optimal Timing 334
Pancreatic Pseudocyst 334
Indications 335
Technical Approaches 335
Surgical Therapy 335
Optimal Timing 335
Vascular Complications 336
Pseudoaneurysms 336 Indications 336
Technical Approaches 336
Surgical Therapy 336
Optimal Timing 337
Extrahepatic Portal Hypertension 337
Indications 337
Surgical Therapy 338
Optimal Timing 338
Bile Duct Obstruction 338
Indications 338
Technical Approaches 338
Surgical Therapy 338
Optimal Timing 338
Duodenal Obstruction 338
Contents xviii
Indications 339
Technical Approaches 339
Surgical Therapy 339
Optimal Timing 339
Pancreatic Cancer 339
Indications 339
Technical Approaches 339
Surgical Therapy 339
Optimal Timing 339
Pancreatic Ascites and Pleural Effusion 339
Indications 340
Technical Approaches 340
Surgical Therapy 340
Optimal Timing 340
Conclusions 340
Acknowledgment 340
References 340
43 Endoscopic Treatment of Complications of Chronic Pancreatitis other than Pseudocyst 342
Jahangeer Basha, Rupjyoti Talukdar, and D. Nageshwar Reddy
Introduction 342
Pancreatic Calculi 342
Pancreatic Duct Strictures 343
Biliary Strictures 344
EUS-guided Celiac Block 344
Pancreatic Duct Leaks 344
EUS-guided Access to MPD 344
References 345
Section III Autoimmune Pancreatitis 347
44 Autoimmune Pancreatitis: Definition, Clinical Presentation, and Classification 349
Miroslav Vujasinovic and J. -Matthias Löhr
Definition and Classification 349
Clinical Presentation 349
Diagnosis 349
Serology 349
Histology 350
Imaging 350
Other Organ Involvement 350
Response to Steroid Treatment 351
Treatment 351
Glucocorticoids 351
Immunosuppressants 352
Outcome and Follow-up in Patients with AIP 352
References 353
45 Diagnosis of Autoimmune Pancreatitis: A Protocol for Clinical Practice 356
Nicolò de Pretis, Antonio Amodio, and Luca Frulloni
Introduction 356
Diagnostic Approach 356
Diffuse AIP (Level 1 Imaging: Typical) 357
Focal AIP (Level 2 Imaging: Indeterminate/Atypical Imaging) 357
References 359
Contents xix
46 Treatment and Follow-up of Autoimmune Pancreatitis in Clinical Practice 360
Sushil Kumar Garg and Suresh T. Chari
Introduction 360
Clinical Characteristics 360
Type 1 AIP (Lymphoplasmacytic Sclerosing Pancreatitis) 360
Type 2 AIP (Idiopathic Duct-centric Pancreatitis) 360
Serology 360
Pathology 360
Pancreatic Imaging 361
Autoimmune Pancreatitis Versus Pancreatic Cancer 361
Diagnosis 361
Definition of Treatment Outcomes 361
Remission 361
Recrudescence 361
Relapse 361
Principles of Management of AIP 362
Indications for Treatment 362
Induction of Remission 362
Steroid Regimen for Induction of Remission 363
Steroid-sparing Agents 363
Adjuvant Therapy 363
Diabetes Mellitus 363
Obstructive Jaundice 363
Exocrine Insufficiency 363
Patient Follow-up 363
Initial Follow-up to Assess Response to Induction 363
How to Taper Steroids 363
Prevention of Relapse 364
Choice of Treatment for Prevention of Relapse 364
Treatment of Relapses 364
Monitoring of Medication Side Effects 365
Summary 365
References 366
Section IV Cystic Fibrosis (CFTR)-associated Pancreatic Disease 369
47 CFTR-associated Pancreatic Disease: Genotype–Phenotype Correlations and Impact of CFTR-modifying Therapy 371
Aimee Joy Wiseman and Chee Y. Ooi
Introduction 371
CFTR Gene and Protein 371
CFTR Mutation Classes 371
Genotype–Phenotype Correlations in CF 372
Genotype–Phenotype Correlations in Exocrine Pancreas Status in CF 372
Pancreatic Insufficiency Prevalence Score and Genotype–Phenotype Correlations in Pancreatitis in CF 373
The Pancreas in Cystic Fibrosis and CFTR-related Disorders 374
Pathogenesis of CFTR-related Pancreatitis 375
Pancreatic cystosis 375
CFTR-modifying Therapies 375
Conclusion 376
References 376
Contents xx
48 Nutritional Therapy, Pancreatic Exocrine Insufficiency, and Pancreatic Enzyme
Replacement Therapy in Cystic Fibrosis: a Protocol for Clinical Practice 379
Jefferson N. Brownell, Laura Padula, Elizabeth Reid, Virginia A. Stallings, and Asim Maqbool
Introduction 379
Mechanisms of Pancreatic Exocrine Insufficiency 380
Diagnosis of Pancreatic Exocrine Insufficiency 380
Nutritional Consequences and Treatment of Pancreatic Exocrine Insufficiency 381
Follow-up Care of Patients with Pancreatic Exocrine Insufficiency 385
Future of CF Nutrition Care 385
References 385
Section V Pancreatic Cancer 389
49 Epidemiological Impact of Pancreatic Cancer 391
Patrick Maisonneuve
Current Burden of Pancreatic Cancer 391
Time Trends 392
Risk Factors for Pancreatic Cancer 395
Heritability 395
Other Risk Factors 395
Attributable Fraction of Pancreatic Cancer due to Potentially Modifiable Risk Factors 398
Future Burden of Pancreatic Cancer 398
Conclusion 399
References 401
50 Molecular and Genetic Basis of Pancreatic Carcinogenesis: Which Concepts are Clinically Relevant? 404
Ihsan Ekin Demir, Carmen Mota Reyes, Elke Demir, and Helmut Friess
Introduction 404
Individual Therapy Based on the Genomic and Transcriptomic Traits of Pancreatic Cancer 404
Organoids for Response Prediction 405
Enhancing the Activation of Immune Surveillance and Inhibition of Immune Suppression 406
Exploiting the Metabolic Alterations in Pancreatic Cancer Cells 406
Targeting the Tumor Stroma 407
Summary 407
References 407
51 New-onset Diabetes as a Harbinger of Pancreatic Cancer: is Early Diagnosis Possible? 409
Dana K. Andersen, Suresh T. Chari, Eithne Costello, Tatjana Crnogorac-Jurcevic, Phil A. Hart, Anirban Maitra, and Stephen J. Pandol
Introduction 409
Epidemiology of DM in PDAC 409
Dual Causality of DM and PDAC 409
Evidence for NOD being a Paraneoplastic Process 410
Using NOD for Early Detection of PDAC 410
The Need for Early Detection of PDAC to Improve Overall Survival 410
Why NOD is the Leading Candidate for Early Detection 411
Challenges and Opportunities of Studying NOD: Finding the High-risk Cohort 411
Methods to Enrich the NOD Cohort to Screen for PDAC 412
The Role of T3cD and the Significance of New-onset T3cD 412
Statistical Modeling Using Clinical and Algorithmic Identification 412
Contents xxi
Biomarkers of T3cD and PDAC-DM 413
T3cD Biomarker 413
PDAC-DM Biomarkers 413
Current Research Endeavors 413
The CPDPC NOD Study 413
The Cancer Research UK-funded UK Early Detection Initiative Study 414
The CPDPC DETECT Study 414
Commonalities of the Investigative Approaches in the United States and the UK 414
Challenges of Studying NOD Secondary to PDAC 414
Conclusions and Recommendations to Practitioners 415
Acknowledgments 415
References 415
52 Pancreatic Cancer Screening: Target Populations, Methods, and Protocols for Clinical Practice 418
Christopher Paiji, Anne Marie Lennon, and Elham Afghani
Introduction 418
Target Populations 418
Germline Genetic Mutations Associated with Pancreatic Cancer 418
Peutz–Jeghers Syndrome 418
Hereditary Pancreatitis 418
Familial Atypical Multiple Mole Melanoma 418
Hereditary Breast and Ovarian Cancer 419
Lynch Syndrome 419
Ataxia Telangiectasia 419
Familial Pancreatic Cancer Families 419
Screening Modality 420
Imaging 420 Biomarkers 420
Screening Protocol 420
Who Should be Screened and When? 420
How Should you Screen? 421
Outcomes of Screening and Surveillance Programs 421
Cost-effectiveness of Pancreatic Cancer Screening Programs 422
Conclusion 422
Acknowledgments 422
References 422
53 Clinical Usefulness of Biological Markers in Pancreatic Cancer 425
David Anz, Ignazio Piseddu, Marlies Köpke, Ujjwal M. Mahajan, and Julia Mayerle
Introduction 425
Challenges in Early Detection of Pancreatic Cancer 425
Role of Clinically Established Biomarkers of Pancreatic Cancer 426
Early Cancer Detection by Novel Biomarkers 426
Metabolomics 426
Circulating Tumor Cells 427
Cell-free DNA 427
Cell-free MicroRNA 428
Exosomes 428
Summary 430
References 430
54 Staging Classification and Stratification of Pancreatic Cancer for Clinical Practice 433
Akhil Chawla and Andrew J. Aguirre
Introduction 433
Clinical Staging 433
Contents xxii
Additional Prognostic Factors 434
Clinically Relevant Molecular Features 434
Imaging Classification of Non-metastatic Disease 435
Imaging for Staging 437
Computed Tomography 437
Magnetic Resonance Imaging 437
Positron Emission Tomography 437
Endoscopic Ultrasound 437
Suggested Radiology Report Format 438
Evaluating Response to Neoadjuvant Therapy 438
Clinical Evaluation 438
Pathological Evaluation 438
Future Directions 439
Acknowledgments 439
References 439
55 Imaging Diagnosis and Staging of Pancreatic Cancer: Which Methods are Essential and What Information Should they Provide? 443
Megan H. Lee and Elliot K. Fishman
Introduction 443
CT Technique 443
Anatomy 443
Pancreatic Adenocarcinoma 444
Tumor Detection 444
Initial Staging 444
Local Invasion 445
Metastatic Disease 446
Postsurgical Imaging 447
Normal Postsurgical Appearance 447
Postsurgical Complications 448
Recurrent and Metastatic Disease 448
Conclusion 448
References 448
56 The Role of Endoscopic Ultrasound and Associated Methods (Elastography, Contrast Enhancement) in the Diagnosis and Assessment of Resectability of Pancreatic Cancer 449
Marc. Giovannini
Introduction 449
Endoscopic Ultrasound for the Diagnosis and Staging of Pancreatic Cancer 449
Classification of Pancreatic Cancer According to EUS Findings 449
Role of EUS in the Diagnosis of Pancreatic Cancer 450
Accuracy of EUS Compared to Cross-sectional Imaging Techniques for the Assessment of Locoregional Extension of Pancreatic Cancer 450
Accuracy for T and N Staging 450
Evaluation of Vascular Involvement 450
Nodal Invasion 451
EUS-guided Fine Needle Biopsy 451
EUS Elastography 452
Theory and Technical Aspects of Elastography 452
Role of EUS Elastography in the Diagnosis of Pancreatic Cancer 452
Contrast-enhanced EUS 453
General Considerations 453
Commercially Available Ultrasound Contrast Agents in Europe 455
Role of Contrast-enhanced EUS in the Diagnosis of Pancreatic Cancer 456
Conclusion 456
References 456
Contents xxiii
57 EUS-Guided FNA/FNB for Pancreatic Solid Lesions: When is it Indicated and What is the Optimal Technical Approach? 460
Mihai Rimbaș, Gianenrico Rizzatti, and Alberto Larghi
Introduction 460
Indications for Performing EUS-guided Tissue Acquisition 460
Optimal Technical Approach to EUS Tissue Acquisition 462
General Rules for Performing EUS-TA 464
EUS-guided Fine Needle Aspiration 464
Number of Passes 464
Needle Size 468
Use of Suction 468
Use of the Stylet 468
EUS-guided Fine Needle Biopsy 468
Conclusions 468
Acknowledgment 468
References 469
58 Surgical Treatment of Resectable Pancreatic Cancer: What is the Optimal Strategy? 472
Jan G. D’Haese, Bernhard W. Renz, and Jens Werner
Introduction 472
Standard Resections and Lymphadenectomy for Resectable Pancreatic Cancer 472
Pancreaticoduodenectomy (Kausch–Whipple Procedure) 472
Pancreatic Left Resection 473
Minimally Invasive Surgery 474
Extended Resections 474
Future Perspectives 475
References 476
59 Complications After Pancreatic Surgery: How to Deal with Them? 477
Tommaso Giuliani, Giovanni Marchegiani, Giuseppe Malleo, and Claudio Bassi
Introduction 477
Postoperative Pancreatic Fistula 477
Definition and Classification 477
Incidence and Risk Factors 477
Mitigation Strategies and Treatment 478
Post-pancreatectomy Hemorrhage 479
Delayed Gastric Emptying 480
Biliary Leakage 481
Chyle Leak 481
Enhanced Recovery After Surgery Policies and Centralization 483
Conclusion 483
References 484
60 Neoadjuvant Treatment of Pancreatic Cancer: When and How? 488
Marta Sandini, Thilo Hackert, Ulla Klaiber, Markus W. Büchler, and John P. Neoptolemos
Background 488
What we have Learnt about Pancreatic Cancer from Adjuvant Therapy Trials 488
The Relevance of a Positive Resection Margin, Local Recurrence and Overall Survival 488
Neoadjuvant Therapy 489
Rationale for Neoadjuvant Chemotherapy 489
Resectable Pancreatic Cancer 489
Borderline Resectable and Locally Advanced Pancreatic Cancer 489
Guidelines for Neoadjuvant Therapy 489
Contents xxiv
Classification of Resectability 490
Neoadjuvant Trials in Resectable and Borderline Resectable Pancreatic Cancer 490
Neoadjuvant Trials in Borderline Resectable Pancreatic Cancer 490
Neoadjuvant Trials in Resectable and Borderline Pancreatic Cancer 496
Neoadjuvant Treatment for Borderline Resectable and Unresectable Locally
Advanced Pancreatic Cancer 496
Surgical Approaches Following Neoadjuvant Treatment for Borderline and Unresectable Locally Advanced Pancreatic Cancer 497
Conclusions 497
References 498
61 Adjuvant Therapy in Pancreatic Cancer: Options, Safety, and Outcomes 501
Jean-Luc Van Laethem
Introduction 501
Brief History and Development of Adjuvant Therapy 501
Recent Phase III Trials Evaluating Combination Chemotherapy 502
Current Standards and Choices in Adjuvant Therapy 502
Future Perspectives 504
Summary 504
References 504
62 Management of Pain in Pancreatic Cancer: An Algorithm for Clinical Routine 506
J. Enrique Domínguez-Muñoz
Relevance of Abdominal Pain in Pancreatic Cancer 506
Approach to Pain Management in Pancreatic Cancer 506
Pain Assessment 506
What is the Most Likely Cause of Pain? 507
Cancer Treatment 507
Psychological Support 507
Nutritional Management and Treatment of Pancreatic Exocrine Insufficiency 508
Pain Therapy in Pancreatic Cancer 508
Pharmacological Therapy 508
Interventional Neurolytic Methods 509
Other Therapies 510
Management of Pain in Pancreatic Cancer: An Algorithm for Clinical Routine 511
References 512
63 EUS-guided Celiac Plexus Neurolysis for Pain in Pancreatic Cancer: When and How? 514
Jonathan M. Wyse and Anand V. Sahai
Introduction 514
When EUS-CPN Should be Considered 514
Safety of EUS-CPN 515
Celiac Ganglia Neurolysis 516
How to Inject and What to Expect: Unilateral vs. Bilateral Injection 516
Is the Future of EUS-CPN Neurolysis with a Different Neurolytic? 517
Summary 517
References 518
64 The Role of Endoscopy in the Management of Unresectable Pancreatic Cancer 520
Jaimin P. Amin, Ajaypal Singh, and Irving Waxman
Background 520
Malignant Biliary Obstruction 520
Newer Advances in Endoscopic Palliation of Biliary Obstruction 523
Intraductal Radiofrequency Ablation 523
Contents xxv
EUS-guided Biliary Access and Drainage 523
Gastroduodenal Outlet Obstruction 524
EUS-guided Gastrojejunostomy 526
Tumor-related Bleeding 527
The Future 527
Conclusions 527
References 528
65 Chemotherapy for Nonresectable Pancreatic Cancer 530
Raquel Fuentes, Juan José Serrano, Mercedes Rodríguez, and Alfredo Carrato
Introduction 530
First Line 530
Single-agent Chemotherapy 530
Gemcitabine 530
Oral Fluoropyrimidines: Capecitabine and S-1 531
Fluorouracil-based Combination Regimens 531
Gemcitabine Combinations 531
Gemcitabine plus Nab-paclitaxel 531
Gemcitabine plus Capecitabine or S-1 532
Gemcitabine plus Erlotinib and Other Molecularly Targeted Agents 532
Second Line 532
After First-line Gemcitabine 532
Liposomal Irinotecan (MM-398, Onivyde) 532
Irinotecan 533
Oxaliplatin-based Regimens 533
Other Oxaliplatin-based Regimens 533
Other Regimens 533
After First-line FOLFIRINOX 533
Genetic Testing 533
Deficient Mismatch Repair/High Level of Microsatellite Instability 534
BRCA Mutation Carriers 534
Conclusions 534
References 535
66 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Pancreatic Cancer 538
Sarah Powell-Brett and Keith J. Roberts
Mechanisms of Pancreatic Exocrine Insufficiency in Pancreatic Cancer 538
PEI in Irresectable Pancreatic Cancer 538
PEI in Resectable Pancreatic Cancer 538
Symptoms of PEI 540
Diagnosis of PEI in Pancreatic Cancer 541
Treatment of PEI with PERT 542
Treatment Dosing 542
Gastric Barrier: pH and Gastric Emptying 542
PERT in Pancreatic Cancer 543
PERT in Unresectable Pancreatic Cancer 543
PERT in Resectable Pancreatic Cancer 543
Overall Survival and Quality of Life Benefit of PERT in Pancreatic Cancer 544
Undertreatment of PEI 544
Key Recommendations 545
References 545
Contents xxvi
67 Nutrition and Pancreatic Cancer 548
Mary Phillips and Oonagh Griffin
Introduction 548
Impact of Pancreatic Ductal Adenocarcinoma on Nutrient Metabolism 548
Pancreatic Exocrine Insufficiency 548
Cancer Cachexia and PDAC 549
Treatment Strategies for Malnutrition in Pancreatic Cancer 549
Locally Advanced and/or Metastatic Disease 549
Resectable Pancreatic Cancer 550
Preoperative Considerations 550
Postoperative Nutritional Support 550
Post-discharge Nutrition 551
Survivorship 551
Conclusion 552
References 552
68 Present and Future of Local Therapies for Unresectable Pancreatic Cancer 555
Sabrina Gloria Giulia Testoni, Gemma Rossi, Livia Archibugi, and Paolo Giorgio Arcidiacono
Introduction 555
Direct Antitumor Therapy 555
EUS-guided Radiofrequency Ablation 555
EUS-guided Irreversible Electroporation 557
EUS-guided Nd:YAG Laser Ablation 557
EUS-guided Photodynamic Therapy 557
EUS-guided High-intensity Focused Ultrasound 558
EUS-guided HybridTherm Ablation 558
Indirect Antitumor Therapy 559
EUS-guided Fiducial Placement 559
EUS-guided Brachytherapy 560
EUS-guided Fine-needle Antitumor Injection 560
Future Directions 561
References 561
69 New Pharmacological Approaches for Pancreatic Cancer Therapy: A Light at the End of the Tunnel? 564
Vineet K. Gupta, Sulagna Banerjee, and Ashok K. Saluja
Introduction 564
Pancreatic Cancer: Challenges in the Field 564
Tumor Heterogeneity 564
Desmoplasia in the Tumor 565
Late Detection of Disease 566
Surgical Challenges 566
Overcoming Challenges: Therapy against Pancreatic Cancer 566
Targeting EGF 566
Targeting Heat-shock Proteins 567
Antistromal Therapy 567
Immunotherapy 568
Metabolic Inhibitors 568
Conclusion 569
Acknowledgments 569
Disclosures 569
References 569
Contents xxvii
Section VI Cystic Tumors of the Pancreas 573
70 Histological Classification of Pancreatic Cystic Neoplasms 575
Giuseppe Zamboni and Anna Pesci
Introduction 575
Serous Cystic Neoplasm 575
Mucinous Cystic Neoplasm 576
Intraductal Papillary Mucinous Neoplasm 577
Intraductal Oncocytic Papillary Neoplasm 579
Intraductal Tubulopapillary Neoplasm 579
Solid Pseudopapillary Neoplasm 580
References 581
71 Role of Endoscopic Ultrasound and Endoscopic Ultrasound-associated Techniques in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Tumors 584
María-Victoria Alvarez-Sánchez and Bertrand Napoléon
Introduction 584
EUS Imaging 584
EUS-FNA 585
Cytology 585
Cyst Fluid Analysis 586
Molecular Biomarkers 586
EUS-guided Through-the-needle Imaging 587
Cystoscopy 587
Needle-based Confocal Laser Endomicroscopy 587
EUS-guided Through-the-needle Biopsy 588
Summary 589
References 590
72 The Role of Multidetector CT, MRI and MRCP in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Neoplasms 593
Megan H. Lee and Elliot K. Fishman
Introduction 593
CT Technique 593
MRI Technique 593
Cystic Pancreatic Masses 593
Mucinous Cystic Neoplasms 594
Serous Cystadenomas 594
Intraductal Papillary Mucinous Neoplasms 595
Other Cystic Pancreatic Lesions 596
Solid Pseudopapillary Tumor 596
Lymphoepithelial Cysts 596
Neuroendocrine Tumors 597
Conclusion 597
References 598
73 Intraductal Papillary Mucinous Neoplasm: When to Observe, When to Operate, and Optimal Surgical Approach 599
Zhi Ven Fong and Carlos Fernandez-del Castillo
Introduction 599
Clinical Considerations 599
Clinical History 599
Radiographic Features 600
Contents xxviii
Pancreatic Cyst Fluid Analysis 600
IPMN Guidelines 601
International Association of Pancreatology Sendai Guidelines 601
American Gastroenterological Association Guidelines 601
European Evidence-based Guidelines 601
Reconciling the Differences 602
Surveillance Strategy for IPMNS not Meeting Criteria for Resection 604
Optimal Surgical Approach 604
Long-term Follow-up after Surgical Resection 604
Conclusions 605
References 605
74 Cystic Tumors Other than IPMN: When to Observe, When to Operate, and Optimal Surgical Approach 608
John W. Kunstman, and James J. Farrell
Introduction 608
Scope of Pancreatic Cystic Neoplasia 608
Mucinous Cystic Neoplasm 609
Indications for Surgery 609
Approach to Management 611
Serous Cystic Neoplasm 611
Indications for Surgery 612
Approach to Management 613
Solid Pseudopapillary Neoplasm 614
Indications for Surgery 615
Approach to Management 616
Cystic Pancreatic Endocrine Neoplasm 616
Indication for Surgery 617
Approach to Management 617
Other Rare Cystic Neoplasms 617
Lymphoepithelial Cysts 617
Cystic Lymphangioma 618
Cystic Degeneration of Solid Tumors 618
References 619
75 Pancreatic Cystic Tumors: any Role for Local Therapies? 624
Julio Iglesias-Garcia
Introduction 624
Indications for EUS-guided Ablation Therapy 624
Cystic Pancreatic Tumors 625
EUS-guided Therapy 625
Radiofrequency Ablation 625
Alcohol and/or Chemical Ablation 626
Conclusions 628
References 628
Section VII Neuroendocrine and Other Tumors of the Pancreas 631
76 Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors: How to Deal with them in Clinical Practice? 633
Francesca Muffatti, Stefano Partelli, Valentina Andreasi, and Massimo Falconi
Introduction 633
Clinical Presentation 633
Contents xxix
Diagnosis 635
Laboratory 635
Imaging 635
Morphological Imaging 635
Functional Imaging 635
Staging Systems 636
Treatment 637
F-PanNENs 637
Nonfunctioning PanNENs 637
Localized Disease 637
Metastatic Disease 637
Acknowledgments 638
References 639
77 Other less Frequent Pancreatic Tumors: What Should be Known about Clinical Features, Diagnosis and Treatment? 641
Rossana Percario, Paolo Panaccio, Fabio F. di Mola, Pierluigi Di Sebastiano, and Tommaso Grottola
Acinar Cell Carcinoma of Pancreas 641
Definition and Epidemiology 641
Clinical Symptoms 641
Diagnosis 641
Laboratory 641
Radiology 641
Fine-needle Aspiration 641
Treatment 642
Hepatoid Carcinoma of Pancreas 642
Schwannoma of Pancreas 642
Perivascular Epithelial Cell Tumor of Pancreas 642
Hematological Malignancies of Pancreas 643
Non-Hodgkin Lymphoma of the Pancreas 643
Post-transplantation Lymphoproliferative Disorder 643
Granulocytic Sarcoma 643
Multiple Myeloma and Solitary Plasmacytoma 643
Castleman Disease 644
Primary Leiomyoma of Pancreas 644
Primary Leiomyosarcoma of Pancreas 644
Pancreatic Lipoma 644
Pancreatic Liposarcoma 644
Cystic Lymphangioma of Pancreas 645
Squamous-lined Cyst of Pancreas 645
Lymphoepithelial Cyst 645
Epidermoid Cyst 645
Dermoid Cyst or Mature Cystic Teratoma 645
Solid Papillary Neoplasm 646
Adult Pancreatoblastoma 646
Pancreatic Metastasis from Other Tumors 646
Renal Cell Cancer Metastasis 646
Colorectal Cancer Metastasis 646
Melanoma Metastasis 646
Breast Cancer Metastasis 647
Contents xxx
Lung Cancer Metastasis 647
Sarcoma Metastasis 647
References 647
Section VIII Functional Alterations of the Pancreas in Other Clinical Situations 651
78 Diagnosis and Therapy of Exocrine Pancreatic Insufficiency after Gastric and Pancreatic Surgery 653
Raffaele Pezzilli
Introduction 653
Gastrectomy 653
Pathophysiology of EPI 653
How to Assess Pancreatic Function in Gastrectomized Patients 654
Pancreatic Enzyme Replacement Therapy after Gastric Resection 655
Well-being of Gastrectomized Patients with Maldigestion 656
Future Perspectives 656
Pancreatectomy 656
Pathophysiology of EPI 656
How to Assess Pancreatic Function in Pancreatic-resected Patients 657
Pancreatic Enzyme Replacement Therapy after Pancreatic Resection 657
Well-being of Pancreatic-resected Patients with Maldigestion 658
Pancreatic Neoplasm 658
Chronic Pancreatitis 658
Type of Surgery and Reconstruction 659
Future Perspectives 659
References 659
79 Pancreatic Exocrine Insufficiency in Type 1 and Type 2 Diabetes Mellitus: Lessons from Pancreatologists to Diabetologists 662
Philip D. Hardt
Historical Aspects of Pancreatic Diseases and Diabetes Mellitus 662
Pancreatic Exocrine Function in Patients with Diabetes Mellitus 663
Pancreas Morphology in Patients with Diabetes Mellitus 663
Pathophysiological Concepts of Altered Exocrine Pancreas Morphology and Function in Type 1 and Type 2 Diabetes Mellitus 664
Exocrine Pancreatic Pathology as a Consequence of Diabetes Mellitus 664
Exocrine Changes in Type 1 Diabetes Mellitus 664
Exocrine Changes in Type 2 Diabetes Mellitus 664
Exocrine and Endocrine Pathology Caused by one Underlying Disease Process 664
Clinical Impact of Exocrine Disease in Type 1 and Type 2 Diabetes Mellitus 665
Conclusion 665
References 666
80 Diabetes Mellitus Related to Diseases of the Exocrine Pancreas (Pancreatogenic Diabetes): Diagnosis and Treatment 668
David A . Bradley and Phil A. Hart
Introduction 668
Epidemiology 668
Chronic Pancreatitis-related Diabetes Mellitus 669
Post-pancreatectomy Diabetes Mellitus 669
Contents xxxi
