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E-raamat: Clinical Pancreatology for Practising Gastroenterologists and Surgeons

Edited by Juan Enrique Dominguez-Munoz (Department of Gastroenterology, University Hospital of Santiago de Compostela)

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Ilmumisaeg: 17-Mar-2021
Kirjastus: Wiley-Blackwell
Keel: eng
ISBN-13: 9781119570141

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Gastroenterology

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Formaat: EPUB+DRM
Ilmumisaeg: 17-Mar-2021
Kirjastus: Wiley-Blackwell
Keel: eng
ISBN-13: 9781119570141

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Gastroenterology

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Clinical Pancreatology

Since the book Clinical Pancreatology for Practising Gastroenterologists and Surgeons was first published sixteen years ago, the knowledge and clinical management of pancreatic diseases have developed markedly. Thanks to the development of the translational research and the from bench to bedside concept, much progress from the lab has been applied to clinical practice. In addition, several highly relevant clinical trials published over the last years have resulted in the update and optimisation of clinical guidelines.

A new and validated classification of severity and complications of acute pancreatitis is firmly rooted in clinical practice and has been the basis for the development of minimally invasive approaches to pancreatic necrosis. The etiopathogenic knowledge of chronic pancreatitis and other pancreatopaties, like that associated with diabetes mellitus, has developed significantly. Especially important has been the development of the field of cystic pancreatic tumours, which has been reflected in the publication of several guidelines and consensus reports over the last few years. Most research efforts have focused on pancreatic cancer, which have led and will further lead to a significant increase in the therapeutic armamentarium against this devastating disease. Finally, many newly published studies have changed the concept, causes, clinical relevance, diagnosis and treatment of exocrine pancreatic insufficiency.

This new edition of Clinical Pancreatology for Practising Gastroenterologists and Surgeons has enjoyed the collaboration of the world&;s leading experts in each of the areas of clinical pancreatology with the aim of facilitating gastroenterologists, surgeons, oncologists, internists, nutritionists, diabetologists, paediatricians, radiologists, pathologists and other specialists in their decision making when facing patients with pancreatic diseases in their daily clinical practice. All in all, this book supplies an indispensable update of the relevant aspects of clinical pancreatology.

Contributors

xxxiii

Foreword

xlvi

Preface

xlvii

Dedication

xlviii

Section I Acute Pancreatitis

(168)

1 Acute Pancreatitis: An Overview

(14)

Jodie A. Barkin

Jamie S. Barkin

Introduction

(1)

Causes

(3)

Laboratory Diagnosis

(1)

Imaging

(1)

Risk Stratification

(1)

Classification

(1)

Treatment

(3)

Prophylactic Antibiotics

(1)

Nutrition

(1)

Post-discharge Cholecystectomy

(2)

Long-term Sequelae

(1)

References

(5)

2 How to Deal with the Etiological Diagnosis of Acute Pancreatitis in Clinical Practice?

(8)

Soumya Jagannath

Pramod Kumar Garg

Introduction

(1)

Etiological Diagnosis

(5)

Gallstone-induced Pancreatitis

(1)

Microlithiasis

(1)

Alcoholic Pancreatitis

(1)

Drug-induced Pancreatitis

(1)

Other Etiological Diagnoses of Acute Pancreatitis

(1)

Hypercalcemia

(1)

Hypertriglyceridemia

(1)

Smoking

(1)

Type 2 Diabetes Mellitus

(1)

Pancreatobiliary Tumors

(1)

Post-ERCP Pancreatitis

(1)

Single and Double Balloon Enteroscopy

(1)

Congenital Anomalies

(1)

Idiopathic Acute Pancreatitis

(1)

Investigative Work-up

(1)

Concluding Remarks

(1)

References

(3)

3 Definition of Complications and Severity of Acute Pancreatitis for Clinical Practice

(6)

David X. Jin

Peter A. Banks

Julia McNabb-Baltar

Background

(1)

The Atlanta Classification 1992

(1)

The Revised Atlanta Classification 2012

(3)

Definition of Organ Failure and Complications in Acute Pancreatitis

(1)

Organ Failure

(1)

Local Complications

(1)

Systemic Complications

(1)

Definition of Severity in Acute Pancreatitis

(1)

Mild Acute Pancreatitis

(1)

Moderately Severe Acute Pancreatitis

(1)

Severe Acute Pancreatitis

(1)

Limitations of the Revised Atlanta Classification

(1)

The Determinant-Based Classification

(1)

Conclusion

(1)

References

(2)

4 Early Prediction of Severity in Acute Pancreatitis: What can be Done in Clinical Practice?

(9)

Peter J. Lee

Georgios I. Papachristou

Introduction

(1)

Available Prediction Tools

(3)

Volume Deficit

(2)

Inflammatory Response

(1)

Host-related Characteristics

(1)

Age and Comorbidity Burden

(1)

Obesity and Hypertriglyceridemia

(1)

Degree of Parenchymal and Extra-parenchymal Injury

(1)

Scoring Systems

(1)

Limitations and Future of Current Scoring Systems and Predictive Markers

(1)

Artificial Intelligence and Biomarkers: the Future?

(1)

References

(4)

5 Role of CT Scan in Acute Pancreatitis: When is it Indicated and What Information can be Obtained?

(7)

Elham Afghani

Mahya Faghih

Vikesh K. Singh

CT Imaging in Acute Pancreatitis

(3)

Confirming the Diagnosis of AP

(1)

Assessing the Etiology of Acute Pancreatitis

(1)

Assessing the Prognosis of Acute Pancreatitis

(1)

Identifying Local Complications Associated with Acute Pancreatitis

(1)

Pancreatic Necrosis and Peripancreatic Fluid Collections

(1)

Vascular Complications

(1)

Other Complications

(1)

Timing of CT in Acute Pancreatitis

(1)

Limitations of CT Imaging

(1)

Conclusion

(1)

Disclosures

(1)

References

(3)

6 Role of MRI in Acute Pancreatitis: When is it Indicated and What Information can be Obtained?

(6)

Fatih Akisik

Introduction

(1)

MRI and MRCP Protocol for Pancreas Examination

(1)

Interstitial Edematous Pancreatitis

(1)

Necrotizing Pancreatitis

(2)

Complications of Acute Pancreatitis

(1)

Fluid Collections

(1)

Acute Peripancreatic Fluid Collection

(1)

Acute Necrotic Collection

(1)

Pseudocyst

(1)

Walled-off Necrosis

(1)

Vascular Complications

(1)

References

(2)

7 Treatment of Acute Pancreatitis in The Emergency Room: What Should be Done During the First Hours of Disease?

(6)

Thiruvengadam Muniraj

Santhi Swaroop Vege

Introduction

(1)

Early Diagnosis in the Emergency Room

(1)

Initial Work-up for Etiology

(1)

Severity Assessment, Triage, and Disposition

(1)

Specialty Consultation

(1)

Management

(1)

First-line Medical Management: Fluid Resuscitation

(1)

Type of Intravenous Fluid to Administer

(1)

Antibiotics

(1)

Pain Control

(1)

Nutrition

(1)

Summary

(1)

References

(3)

8 Acute Pancreatitis: A Practical Guideline for the Monitoring and Treatment of Systemic Complications

(7)

Enrique de Madaria

Felix Zubia-Olaskoaga

Introduction

(1)

Acute Pancreatitis and Systemic Complications: Definitions, Importance, and Incidence

(1)

Monitoring Respiratory Function and Management of Respiratory Failure

(1)

Shock: Volume Management and Hemodynamic Monitoring

(1)

Acute Renal Failure: Early Detection and Management

(1)

Other Systemic Complications Associated with Acute Pancreatitis

(1)

Hypocalcemia

(1)

Disseminated Intravascular Coagulation

(1)

Gastrointestinal Bleeding

(1)

Pancreatic Encephalopathy and Posterior Reversible Encephalopathy Syndrome

(1)

Abdominal Compartment Syndrome

(1)

References

(3)

9 Guidelines for the Treatment of Pain in Acute Pancreatitis

(6)

Laszlo Czako

Introduction

(1)

Nonsteroidal Anti-inflammatory Drugs

(1)

Opioid Analgesics

(1)

Epidural Analgesia

(1)

Local Anesthetics

(1)

Summary

(1)

References

(2)

10 Nutrition in the Acute Phase of Pancreatitis: Why, When, How and How Long?

(6)

Angela Pham

Chris E. Forsmark

Why

(1)

When

(1)

How

(2)

What to Feed

(1)

References

(3)

11 Oral Refeeding in Acute Pancreatitis: When and How Should it be Restarted?

(5)

Jose Larino-Noia

Daniel de la Iglesia-Garcia

Introduction

(1)

What is the Optimal Timing of Refeeding in AP?

(1)

How Should Oral Refeeding be Scheduled?

(1)

What are the Predictors of Oral Feeding Intolerance in AP Patients?

(2)

Summary and Recommendations

(1)

References

(2)

12 Pharmacological Therapy for Acute Pancreatitis: Any Light at the End of the Tunnel?

(12)

Rajarshi Mukherjee

Muhammad Awais

Wenhao Cai

Wei Huang

Peter Szatmary

Robert Sutton

Introduction

(1)

Calcium Toxicity

(1)

Mitochondrial Dysfunction

(2)

Autophagy

(1)

Acinar Cell Secretion, Serine Proteases, and Serine Protein Kinases

(1)

Immune Cells/Inflammation

(2)

CFTR

(1)

Design of Future Clinical Trials

(1)

Conclusion

(1)

References

(5)

13 Indication and Optimal Timing of ERCP in Acute Pancreatitis

(5)

Theodor Voiosu

Ivo Ba§koski

Guido Costamagna

Introduction

(1)

ERCP in the Setting of Acute Biliary Pancreatitis

(2)

Urgent ERCP

(1)

Elective ERCP

(1)

Additional Applications of ERCP in the Setting of Acute Pancreatitis

(1)

Conclusions

(1)

Disclosures

(1)

References

(2)

14 How to Deal with Infected Pancreatic Necrosis?

100

(5)

J. Enrique Dominguez-Munoz

Introduction

100

(1)

Prevention of Infection of (Peri)pancreatic Necrosis

100

(1)

Diagnosis of Infected (Peri)pancreatic Necrosis

101

(1)

How to Deal with Infected (Peri)pancreatic Necrosis

101

(1)

Systemic Antibiotics

101

(1)

Endoscopic or Percutaneous Drainage

101

(1)

Endoscopic or Laparoscopic Necrosectomy

102

(1)

References

102

(3)

15 Minimally Invasive Surgical Necrosectomy in Clinical Practice: Indications, Technical Issues, and Optimal Timing

105

(8)

Patricia Sanchez- Velazquez

Fernando Burdio

Ignasi Povest

Introduction

105

(1)

Percutaneous Drainage

105

(1)

Sinus Tract Endoscopy

106

(1)

Endoscopic (Endoluminal) Approach

106

(2)

Retroperitoneal Approach

108

(1)

Laparoscopic Transperitoneal Approach

109

(2)

References

111

(2)

16 Endoscopic Necrosectomy in Clinical Practice: Indications, Technical Issues and Optimal Timing

113

(7)

Jodie A. Barkin

Andres Gelrud

Introduction

113

(1)

Management of Symptomatic Pseudocysts

114

(1)

Management of Symptomatic Walled-off Necrosis

114

(3)

Indications and Timing for Intervention

114

(1)

Choosing the Best Interventional Option: the Step-up Approach

115

(1)

Methods of Endoscopic Necrosectomy and Stent Choice

116

(1)

Conclusion

117

(1)

References

118

(2)

17 Management of Acute Pancreatic Pseudocyst: When to Observe, When and How to Drain?

120

(6)

Muhammad F. Dawwas

Kofi W. Oppong

Introduction

120

(1)

Evaluation

120

(2)

Drainage Therapy

122

(2)

Disconnected Pancreatic Duct Syndrome

124

(1)

Complications

124

(1)

Conclusion

124

(1)

References

125

(1)

18 The Disconnected Main Pancreatic Duct Syndrome: How to Proceed in Clinical Practice?

126

(6)

Mario Pelaez-Luna

Andrea Soriano-Rios

Luis Uscanga-Dominguez

Introduction

126

(1)

Epidemiology

126

(1)

Risk Factors and Predictors of DPDS

126

(1)

Clinical Significance

126

(1)

Clinical Presentation

127

(1)

Diagnosis

127

(1)

Treatment

128

(1)

Conclusions

129

(1)

References

130

(2)

19 Vasculature Complications in Pancreatitis: How to Deal with Them?

132

(9)

Daniel G. McCall

Timothy B. Gardner

Venous Complications

132

(3)

Splanchnic Thrombosis Rates

132

(1)

Risk Factors for Thrombosis

132

(1)

Clinical Findings

133

(1)

Screening

133

(1)

Splenic Vein Thrombosis

133

(1)

Portal Vein Thrombosis

133

(1)

Management of Visceral Vein Thrombosis

134

(1)

Anticoagulation

134

(1)

Surgical Management

135

(1)

Miscellaneous Venous Complications

135

(1)

Bowel Wall Ischemia

135

(1)

Portal Vein-Pseudocyst Fistula

135

(1)

Arterial Complications

135

(3)

Pseudoaneurysm

135

(1)

Pseudoaneurysm and Risk of Rupture

136

(1)

Hemosuccus Pancreaticus

137

(1)

Imaging of Pseudoaneurysm or Potential Hemorrhage

137

(1)

Ruptured Pseudoaneurysm Management

138

(1)

Summary

138

(1)

References

138

(3)

20 Acute Relapsing Pancreatitis: What can be Done to Prevent Relapses?

141

(10)

Jorge D. Machicado

Dhiraj Yadav

Introduction

141

(1)

Definition

141

(1)

Burden

141

(1)

Demographics

142

(1)

Etiology

142

(1)

Diagnostic Work-up

143

(1)

Natural History and Risk of Progression

144

(2)

Preventing Recurrences and Disease Progression

146

(1)

Conclusion

147

(1)

Acknowledgment

147

(1)

References

147

(4)

21 Diagnosis and Therapeutic Approach to Pancreatic Exocrine Insufficiency after Acute Pancreatitis

151

(7)

Hester C. Timmerhuis

Christa J. Sperna Weiland

Hjalmar C. van Santvoort

Introduction

151

(1)

Symptoms

151

(1)

Diagnosis

152

(1)

Management

152

(2)

Summary

154

(1)

References

155

(3)

22 Asymptomatic Chronic Elevation of Serum Pancreatic Enzymes: How to Deal with It?

158

(11)

Giuseppe Vanella

Paolo Giorgio Arcidiacono

Gabriele Capurso

Introduction

158

(1)

Physiology of Pancreatic Enzymes

158

(1)

Pancreatic Abnormalities in Patients with Pancreatic Hyperenzymemia

158

(2)

Pancreatic Hyperenzymemia: A Clue to Malignancy?

160

(1)

Pancreatic Abnormalities at Second-level Imaging

160

(1)

Gastrointestinal Diseases and Pancreatic Hyperenzymemia

160

(1)

Inflammatory Bowel Disease

160

(1)

Celiac Disease

160

(1)

Liver Disease

161

(1)

Others

161

(1)

Macroenzymemia

161

(1)

Systemic Conditions Associated with Hyperenzymemia

161

(1)

Familial Aggregation and Genetics

161

(1)

Drug-induced Hyperenzymemia

161

(1)

Extrapancreatic Abnormalities in Patients with Hyperenzymemia

162

(1)

Salivary Gland Diseases

162

(1)

Renal Insufficiency

162

(1)

Hyperenzymemia and Cancers

162

(1)

Eating Disorders

162

(1)

Others

162

(1)

Benign Pancreatic Hyperenzymemia (Gullo Syndrome)

163

(1)

Clinical Features

163

(1)

Physiopathology

163

(1)

Algorithm for Management of CAPH (Figure 22.2)

163

(2)

Clinical History and Laboratory Evaluation

163

(1)

Isolated Hyperamylasemia

164

(1)

Pancreatic Hyperamylasemia and/or Hyperlipasemia

165

(1)

Conclusions

165

(1)

References

165

(4)

Section II Chronic Pancreatitis

169

(178)

23 Definition and Etiology of Chronic Pancreatitis: What is Relevant for Clinical Practice?

171

(9)

David C. Whitcomb

Definition of Key Terms and Concepts

171

(3)

Dysfunction

171

(1)

Disorder

171

(1)

Disease

171

(1)

Syndrome

172

(1)

Diagnosis

172

(1)

Differential Diagnosis

172

(1)

Risk Factor

172

(1)

Etiology

172

(1)

Biomarkers

172

(2)

Modern Western Medicine

174

(1)

Precision Medicine

174

(1)

Traditional Definitions of Chronic Pancreatitis

174

(1)

Mechanistic Definition of Chronic Pancreatitis

174

(1)

Progressive Model of CP

175

(1)

Risk Factors and Etiologies

175

(1)

Pathogenic Genetic Mutations

176

(1)

Genetic Risk Factors

176

(1)

Subtypes of Inflammatory Diseases of the Pancreas

176

(1)

Acute Pancreatitis

176

(1)

Recurrent Acute Pancreatitis

177

(1)

Hereditary Pancreatitis

177

(1)

Familial Pancreatitis

177

(1)

Tropical Pancreatitis

177

(1)

Mendelian Syndromes Involving the Pancreas

177

(1)

Complex Pancreatic Disorders

177

(1)

Minimal Change Chronic Pancreatitis

177

(1)

References

177

(3)

24 Epidemiology of Chronic Pancreatitis: An Infrequent Disease or an Infrequently Diagnosed Disease?

180

(5)

Philippe Levy

Vinciane Rebours

Why is Chronic Pancreatitis Epidemiology so Imprecise?

180

(1)

Epidemiology

181

(1)

Why are Reported Data on Incidence and Prevalence of Chronic Pancreatitis Discrepant?

182

(1)

General Characteristics of Patients with Chronic Pancreatitis

182

(1)

Mortality

182

(1)

Conclusion

183

(1)

References

183

(2)

25 Alcoholic Chronic Pancreatitis and the Impact of Alcohol and Smoking Cessation in Chronic Pancreatitis

185

(8)

Jeremy S. Wilson

Romano C. Pirola

Minoti V. Apte

Introduction

185

(1)

Epidemiology

185

(1)

Direct Cellular Effects of Alcohol on the Pancreas

185

(2)

Metabolism of Alcohol by the Pancreas

185

(1)

Effects of Ethanol on Pancreatic Acinar Cells

186

(1)

Effects of Ethanol on Pancreatic Stellate Cells

187

(1)

Effects of Ethanol on Pancreatic Duct Cells

187

(1)

Individual Susceptibility to Alcoholic Pancreatitis

187

(1)

Impact of Alcohol and Smoking Cessation

188

(1)

Summary

189

(1)

References

189

(4)

26 What is Relevant on Genetics in Chronic Pancreatitis for Clinical Practice? What Genes and When to Evaluate Them?

193

(5)

Jonas Rosendahl

Introduction

193

(1)

How to Screen

193

(1)

Probability of Identifying Genetic Variants in CP Patients

193

(1)

Which Genes are Clinically Relevant?

193

(2)

Screening for Cystic Fibrosis Transmembrane Conductance Regulator Gene Variants

195

(1)

What to do When a Variant has been Identified?

195

(1)

Increased Risk for Pancreatic Cancer in Chronic Pancreatitis Patients

195

(1)

How can Genetic Association Studies Change our Clinical Practice?

196

(1)

References

196

(2)

27 Pancreas Divisum and Other Potential Obstructive Causes of Chronic Pancreatitis: When and How to Treat Them?

198

(10)

Matthew J. DiMagno

Erik-Jan Wamsteker

Introduction

198

(1)

Idiopathic Pancreatitis

198

(1)

Pancreas Divisum

199

(3)

Criterion 1: The Prevalence of PD Should be Greater in Pancreatitis than in the General Population

200

(1)

Criterion 2: A Dilated Dorsal Duct System Should be Present if There is a Functionally Significant Obstruction

200

(1)

Criterion 3: Pathological Changes Should Develop only in the Dorsal Duct

201

(1)

Criterion 4: Drainage Procedures of the duct of Santorini Should Reduce the Frequency or Severity of Recurrent Attacks of Pancreatitis

201

(1)

Alternate Genetic Explanations for Pancreatitis and PD

202

(1)

Other Potential Obstructive Causes of Chronic Pancreatitis

202

(1)

(Pre)Neoplastic Causes

202

(1)

Anatomical Congenital Variations Affecting the Biliopancreatic Ductal System

202

(1)

Acquired Obstructive Conditions

203

(1)

Non-neoplastic Causes

203

(1)

Periampullary Obstruction: Duodenal Diverticula and Other Causes of Periampullary Obstruction

203

(1)

Main Pancreatic Duct Stricture

204

(1)

Postsurgical Pancreatic Duct Stricture

204

(1)

Postsurgical Intestinal Obstruction

204

(1)

Pancreatic Sphincter of Oddi Dysfunction

204

(1)

Disclosures

204

(1)

References

204

(4)

28 What to do in Clinical Practice Before Defining a Chronic Pancreatitis as Idiopathic? A Practical Protocol

208

(10)

Felix Lammerhirt

Frank Ulrich Weiss

Markus M. Lerch

Introduction

208

(1)

Etiologies of Chronic Pancreatitis

208

(2)

Alcoholic Chronic Pancreatitis

208

(1)

Hypertriglyceridemia-induced Chronic Pancreatitis

209

(1)

Hypercalcemia-induced Chronic Pancreatitis

209

(1)

Autoimmune Chronic Pancreatitis

209

(1)

Genetic Risk Factors and Hereditary Chronic Pancreatitis

210

(1)

Rare Causes of Chronic Pancreatitis

210

(1)

How to Classify Chronic Pancreatitis as Idiopathic

210

(1)

Diagnostic Approach

210

(4)

Anamnestic Investigation and Physical Examination

211

(1)

Laboratory Chemistry

211

(1)

Basic Laboratory Tests

211

(1)

Specific Tests to Address the Underlying Etiology of CP

212

(1)

Genetic Testing

212

(1)

Imaging Techniques

212

(1)

Transabdominal Ultrasound

212

(1)

Endoscopic Ultrasound

213

(1)

Endoscopic Retrograde Cholangiopancreatography

214

(1)

Computed Tomography and Magnetic Resonance Imaging

214

(1)

Conclusion

214

(1)

References

215

(3)

29 Computed Tomography for the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice

218

(9)

Roberto Garcia-Figueiras

Sandra Baleato-Gonzalez

Gonzalo Tardaguila de la Fuente

Introduction

218

(1)

Conventional CT in the Evaluation of Chronic Pancreatitis

218

(3)

Chronic Calcifying Pancreatitis

218

(1)

Chronic Obstructive Pancreatitis

219

(2)

Groove Pancreatitis

221

(1)

Autoimmune Pancreatitis

221

(1)

Complications Associated with Chronic Pancreatitis

221

(1)

Advanced CT Techniques

221

(2)

CT Volumetry and Assessment of Pancreatic Attenuation

221

(1)

Dual-energy or Spectral CT

222

(1)

Perfusion CT

222

(1)

Future Challenges in CT Imaging

223

(1)

Conclusion

224

(1)

References

224

(3)

30 Role of MRI and MRCP in the Diagnosis, Evaluation of Severity, and Detection of Complications of Chronic Pancreatitis in Clinical Practice

227

(6)

Jordan K. Swenson

Temel Tirkes

Introduction

227

(1)

Diagnosis

227

(2)

Severity

229

(1)

Complications

230

(1)

Conclusion

230

(1)

References

231

(2)

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

(10)

Julio Iglesias-Garcia

Introduction

233

(1)

EUS in the Diagnosis of Chronic Pancreatitis

233

(5)

Standard EUS for the Diagnosis of Chronic Pancreatitis

233

(3)

Advanced EUS for the Diagnosis of Chronic Pancreatitis

236

(1)

EUS plus Endoscopic Pancreatic Function Test

236

(1)

EUS-guided Elastography and Contrast Enhancement

237

(1)

EUS-guided Tissue Acquisition

237

(1)

EUS for the Evaluation of Complications of Chronic Pancreatitis

238

(2)

EUS for Evaluating the Presence of Pancreatic Exocrine Insufficiency

238

(1)

EUS for the Detection of Pancreatic Malignancy in Chronic Pancreatitis

239

(1)

EUS-guided Tissue Acquisition

239

(1)

EUS-guided Elastography and CEH-EUS

239

(1)

Conclusions

240

(1)

References

240

(3)

32 Endoscopic Pancreatic Function Test for the Functional Diagnosis of Chronic Pancreatitis: Indications and Practical Protocol

243

(7)

Luis F. Lara

Darwin L. Conwell

Introduction

243

(1)

History of Pancreas Function Tests

243

(1)

Pancreas Function Tests

244

(3)

Endoscopic Pancreas Function Tests

245

(1)

Pancreatic Function Test Performance

245

(1)

Abridged ePFT

246

(1)

Concerns Regarding Pancreatic Function Tests

246

(1)

Indications for ePFT

246

(1)

Practical Protocol

247

(1)

Conclusions

247

(1)

References

248

(2)

33 Rote of Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis: Which Tests and How Should they be Performed in Clinical Practice?

250

(5)

J. Enrique Dominguez-Munoz

Introduction

250

(1)

Pancreatic Function Tests for the Diagnosis of Chronic Pancreatitis in Patients with Inconclusive Imaging Findings

251

(1)

How to Perform the Secretin-CCK (Cerulein) Test

251

(1)

How to Perform the Endoscopic Pancreatic Function Test

252

(1)

Evaluation of Pancreatic Function as Screening Test for Patients with Clinical Symptoms Suggestive of Chronic Pancreatitis

252

(1)

Use of Fecal Elastase Test in Clinical Practice

253

(1)

References

253

(2)

34 Follow-up of Patients with Chronic Pancreatitis in Clinical Practice: How and What for?

255

(10)

Antonio Mendoza-Ladd

Luis F. Lara

Darwin L. Conwell

Introduction

255

(1)

Pain

255

(2)

Mechanical Obstruction

255

(1)

Neurogenic

255

(1)

Pancreatic Enzyme Replacement Therapy

255

(1)

Antioxidants

256

(1)

Analgesics

256

(1)

Endoscopic Therapy

256

(1)

Surgery

256

(1)

Nutritional Deficiencies

257

(1)

Diabetes

258

(1)

Exocrine Insufficiency

258

(1)

Functional Tests

258

(1)

Direct Tests

258

(1)

Indirect tests

258

(1)

Management of EPI

259

(1)

Final Considerations

259

(1)

Conclusion

260

(1)

References

260

(5)

35 Quality of Life in Chronic Pancreatitis

265

(8)

Colin D. Johnson

Introduction

265

(1)

Assessment

265

(2)

What QOL Questionnaires Measure

265

(1)

Available Questionnaires

266

(1)

EORTC QLQ System

266

(1)

Short Form Questionnaires

266

(1)

PANQOLI

267

(1)

Factors Affecting QOL

267

(2)

Pain

267

(1)

Insomnia and Fatigue

268

(1)

Weight Loss

268

(1)

Pancreatic Exocrine Insufficiency

268

(1)

Psychological Factors

268

(1)

Other Factors

269

(1)

Treatment

269

(2)

Medical Treatment

269

(1)

Pancreatic Enzyme Replacement

270

(1)

Endoscopic and Extracorporeal Therapies

270

(1)

Surgery

270

(1)

Conclusions

271

(1)

References

271

(2)

36 Medical Treatment of Pain in Chronic Pancreatitis: Guidelines for Clinical Practice

273

(10)

Asbjorn Mohr Drewes

Louise Kuhlman

Trine Andresen

Soren Schou Olesen

Introduction

273

(1)

Pathogenesis of Pain

273

(1)

Medical Pain Management

274

(4)

Risk Factors

274

(1)

Enzymes and Antioxidants

274

(1)

Analgesics

275

(1)

Simple Analgesics

275

(1)

Adjuvant Analgesics

275

(1)

Opioids

277

(1)

Alternative Treatments

277

(1)

Personalized Treatment

278

(1)

Pharmacological Considerations

278

(1)

Conclusion

279

(1)

References

279

(4)

37 Endoscopic Treatment of Pain in Chronic Pancreatitis: Indications, Optimal Timing, and Technical Aspects

283

(9)

Pauline M. C. Stassen

Pieter J.F. de Jonge

Jan-Werner Poley

Djuna L. Cahen

Marco J. Bruno

Introduction

283

(1)

Selecting the Right Patient for Endoscopic Therapy: Who and When?

283

(1)

Factors Predictive of Clinical Success

283

(1)

Optimal Timing and Treatment Choice

284

(1)

Treatment of Pancreatic Duct Stones

284

(2)

Extracorporeal Shock-wave Lithotripsy

284

(1)

Technical Aspects

284

(1)

Effectiveness and Safety

285

(1)

Pancreatoscopy-guided Lithotripsy

285

(1)

Technical Aspects

285

(1)

Effectiveness and Safety

286

(1)

Treatment of Pancreatic Duct Strictures

286

(1)

Technical Aspects

286

(1)

Effectiveness and Safety

287

(1)

EUS-guided Pancreaticogastrostomy

287

(1)

Technical Aspects

287

(1)

Effectiveness and Safety

287

(1)

Celiac Plexus Block

288

(1)

Technical Aspects

288

(1)

Effectiveness and Safety

288

(1)

Summary

288

(1)

References

288

(4)

38 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Chronic Pancreatitis: A Practical Protocol

292

(9)

J. Enrique Dominguez-Munoz

Concept of Pancreatic Exocrine Insufficiency

292

(1)

Pathophysiology

292

(1)

Clinical Manifestations

293

(1)

Diagnosis

293

(3)

Tests Evaluating Fat Digestion: Coefficient of Fat Absorption and Breath Test

294

(1)

Tests Evaluating Pancreatic Secretion: Secretin-CCK Test and Fecal Elastase Test

295

(1)

Nutritional Markers for the Diagnosis of PEI

295

(1)

Diagnosis in Clinical Practice

296

(1)

Treatment

296

(2)

Nutritional Therapy

296

(1)

Pancreatic Enzyme Replacement Therapy

297

(1)

When to Prescribe

297

(1)

Aims

297

(1)

Administration

297

(1)

Correct Starting Dose

297

(1)

Efficacy

297

(1)

Unsatisfactory Response

297

(1)

Prevention and Prognosis

298

(1)

References

298

(3)

39 Surgical Treatment of Pain in Chronic Pancreatitis: Indications, Optimal Timing and Technical Approaches

301

(13)

Benjamin P.T. Loveday

John A. Windsor

Introduction

301

(1)

Indications and Contraindications for Surgical Treatment

301

(1)

Diagnostic Work-up

302

(1)

Optimal Timing

302

(1)

Clinical Considerations in Selecting the Surgical Approach

303

(1)

Technical Approaches

303

(5)

Drainage Procedures

303

(1)

Longitudinal Pancreaticojejunostomy (Partington-Rochelle or Puestow)

303

(4)

Combined Drainage and Resection Procedures

307

(1)

Duodenum-preserving Pancreatic Head Resection with End-to-end Pancreaticojejunostomy (Beger)

307

(1)

Berne Modification of the Duodenum-preserving Pancreatic Head Resection with End-to-end Pancreaticojejunostomy

307

(1)

Local Resection of the Pancreatic Head with Longitudinal Pancreaticojejunostomy (Frey)

307

(1)

The "Hamburg" Modification to the Frey Procedure

307

(1)

Resection Procedures

307

(1)

Pancreaticoduodenectomy (Whipple)

307

(1)

Distal Pancreatectomy (with or without Spleen Preservation)

307

(1)

Total Pancreatectomy (with or without Spleen Preservation)

307

(1)

Total Pancreatectomy with Islet Autotransplantation

308

(1)

Denervation Procedures

308

(1)

Celiac Plexus Block

308

(1)

Sympathectomy

308

(1)

Tips and Tricks for Surgical Interventions

308

(1)

Outcomes and Quality of Life after Surgery

308

(1)

Follow-up

309

(1)

Conclusion

309

(1)

References

309

(5)

40 Management of Chronic Pancreatic Pseudocyst: When to Observe, When and How to Drain?

314

(8)

Shyam Varadarajulu

Introduction

314

(1)

Definition of Pseudocyst

314

(1)

When to Observe or Drain

314

(1)

Important Preprocedure Considerations

315

(1)

Procedural Technique: How to Drain

315

(4)

Conventional Transmural Drainage

315

(2)

EUS-guided Drainage

317

(1)

Multistep Technique Using Plastic Stents

317

(1)

Single-step Technique Using LAMS

317

(1)

Special Considerations

317

(1)

Disconnected Pancreatic Duct Syndrome

317

(1)

Ductal Communication with Pseudocyst

318

(1)

Multiple Pseudocysts

319

(1)

Postprocedure Care

319

(1)

Adverse Events

319

(1)

Conclusions

320

(1)

References

320

(2)

41 Vascular Complications in Chronic Pancreatitis

322

(11)

Anil K. Agarwal

Raja Kalayarasan

Amit Javed

Introduction

322

(1)

Arterial Complications

322

(5)

Arterial Pseudoaneurysm in Chronic Pancreatitis

322

(1)

Pathophysiology

322

(1)

Clinical Features

322

(1)

Investigations

323

(1)

Management

323

(4)

Venous Complications

327

(4)

Splenic Vein Thrombosis in Chronic Pancreatitis

327

(1)

Pathophysiology

327

(1)

Clinical Features

327

(1)

Investigations

327

(1)

Management

328

(1)

Splenoportal/Mesenteric Vein Thrombosis

329

(2)

Miscellaneous Venous Complications

331

(1)

References

331

(2)

42 Surgical Therapy of Local Complications of Chronic Pancreatitis: Indications, Technical Approaches, and Optimal Timing

333

(9)

Ricardo Arvizu Castillo

Elena Munoz-Forner

Luis Sabater

The Role of the Surgeon in the Treatment of Local Complications in Chronic Pancreatitis

333

(1)

Pancreatic Duct Strictures

334

(1)

Indications

334

(1)

Surgical Therapy

334

(1)

Optimal Timing

334

(1)

Pancreatic Pseudocyst

334

(2)

Indications

335

(1)

Technical Approaches

335

(1)

Surgical Therapy

335

(1)

Optimal Timing

335

(1)

Vascular Complications

336

(4)

Pseudoaneurysms

336

(1)

Indications

336

(1)

Technical Approaches

336

(1)

Surgical Therapy

336

(1)

Optimal Timing

337

(1)

Extrahepatic Portal Hypertension

337

(1)

Indications

337

(1)

Surgical Therapy

338

(1)

Optimal Timing

338

(1)

Bile Duct Obstruction

338

(1)

Indications

338

(1)

Technical Approaches

338

(1)

Surgical Therapy

338

(1)

Optimal Timing

338

(1)

Duodenal Obstruction

338

(1)

Indications

339

(1)

Technical Approaches

339

(1)

Surgical Therapy

339

(1)

Optimal Timing

339

(1)

Pancreatic Cancer

339

(1)

Indications

339

(1)

Technical Approaches

339

(1)

Surgical Therapy

339

(1)

Optimal Timing

339

(1)

Pancreatic Ascites and Pleural Effusion

339

(1)

Indications

340

(1)

Technical Approaches

340

(1)

Surgical Therapy

340

(1)

Optimal Timing

340

(1)

Conclusions

340

(1)

Acknowledgment

340

(1)

References

340

(2)

43 Endoscopic Treatment of Complications of Chronic Pancreatitis other than Pseudocyst

342

(5)

Jahangeer Basha

Rupjyoti Talukdar

D. Nageshwar Reddy

Introduction

342

(1)

Pancreatic Calculi

342

(1)

Pancreatic Duct Strictures

343

(1)

Biliary Strictures

344

(1)

EUS-guided Celiac Block

344

(1)

Pancreatic Duct Leaks

344

(1)

EUS-guided Access to MPD

344

(1)

References

345

(2)

Section III Autoimmune Pancreatitis

347

(22)

44 Autoimmune Pancreatitis: Definition, Clinical Presentation, and Classification

349

(7)

Miroslav Vujasinovic

J. Matthias Lohr

Definition and Classification

349

(1)

Clinical Presentation

349

(1)

Diagnosis

349

(2)

Serology

349

(1)

Histology

350

(1)

Imaging

350

(1)

Other Organ Involvement

350

(1)

Response to Steroid Treatment

351

(1)

Treatment

351

(1)

Glucocorticoids

351

(1)

Immunosuppressants

352

(1)

Outcome and Follow-up in Patients with AIP

352

(1)

References

353

(3)

45 Diagnosis of Autoimmune Pancreatitis: A Protocol for Clinical Practice

356

(4)

Nicolo de Pretis

Antonio Amodio

Luca Frulloni

Introduction

356

(1)

Diagnostic Approach

356

(3)

Diffuse AIP (Level 1 Imaging: Typical)

357

(1)

Focal AIP (Level 2 Imaging: Indeterminate/Atypical Imaging)

357

(2)

References

359

(1)

46 Treatment and Follow-up of Autoimmune Pancreatitis in Clinical Practice

360

(9)

Sushil Kumar Garg

Suresh T. Chari

Introduction

360

(1)

Clinical Characteristics

360

(1)

Type 1 AIP (Lymphoplasmacytic Sclerosing Pancreatitis)

360

(1)

Type 2 AIP (Idiopathic Duct-centric Pancreatitis)

360

(1)

Serology

360

(1)

Pathology

360

(1)

Pancreatic Imaging

361

(1)

Autoimmune Pancreatitis Versus Pancreatic Cancer

361

(1)

Diagnosis

361

(1)

Definition of Treatment Outcomes

361

(1)

Remission

361

(1)

Recrudescence

361

(1)

Relapse

361

(1)

Principles of Management of AIP

362

(1)

Indications for Treatment

362

(1)

Induction of Remission

362

(1)

Steroid Regimen for Induction of Remission

363

(1)

Steroid-sparing Agents

363

(1)

Adjuvant Therapy

363

(1)

Diabetes Mellitus

363

(1)

Obstructive Jaundice

363

(1)

Exocrine Insufficiency

363

(1)

Patient Follow-up

363

(2)

Initial Follow-up to Assess Response to Induction

363

(1)

How to Taper Steroids

363

(1)

Prevention of Relapse

364

(1)

Choice of Treatment for Prevention of Relapse

364

(1)

Treatment of Relapses

364

(1)

Monitoring of Medication Side Effects

365

(1)

Summary

365

(1)

References

366

(3)

Section IV Cystic Fibrosis (CFTR)-associated Pancreatic Disease

369

(20)

47 CFTR-associated Pancreatic Disease: Genotype-Phenotype Correlations and Impact of CFTR-modifying Therapy

371

(8)

Aimee Joy Wiseman

Chee Y. Ooi

Introduction

371

(1)

CFTR Gene and Protein

371

(1)

CFTR Mutation Classes

371

(1)

Genotype-Phenotype Correlations in CF

372

(1)

Genotype-Phenotype Correlations in Exocrine Pancreas Status in CF

372

(1)

Pancreatic Insufficiency Prevalence Score and Genotype-Phenotype Correlations in Pancreatitis in CF

373

(1)

The Pancreas in Cystic Fibrosis and CFTR-related Disorders

374

(1)

Pathogenesis of CFTR-related Pancreatitis

375

(1)

Pancreatic cystosis

375

(1)

CFTR-modifying Therapies

375

(1)

Conclusion

376

(1)

References

376

(3)

48 Nutritional Therapy, Pancreatic Exocrine Insufficiency, and Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis: a Protocol for Clinical Practice

379

(10)

Jefferson N. Brownell

Laura Padula

Elizabeth Reid

Virginia A. Stallings

Asim Maqbool

Introduction

379

(1)

Mechanisms of Pancreatic Exocrine Insufficiency

380

(1)

Diagnosis of Pancreatic Exocrine Insufficiency

380

(1)

Nutritional Consequences and Treatment of Pancreatic Exocrine Insufficiency

381

(4)

Follow-up Care of Patients with Pancreatic Exocrine Insufficiency

385

(1)

Future of CF Nutrition Care

385

(1)

References

385

(4)

Section V Pancreatic Cancer

389

(184)

49 Epidemiological Impact of Pancreatic Cancer

391

(13)

Patrick Maisonneuve

Current Burden of Pancreatic Cancer

391

(1)

Time Trends

392

(3)

Risk Factors for Pancreatic Cancer

395

(3)

Heritability

395

(1)

Other Risk Factors

395

(3)

Attributable Fraction of Pancreatic Cancer due to Potentially Modifiable Risk Factors

398

(1)

Future Burden of Pancreatic Cancer

398

(1)

Conclusion

399

(2)

References

401

(3)

50 Molecular and Genetic Basis of Pancreatic Carcinogenesis: Which Concepts are Clinically Relevant?

404

(5)

Ihsan Ekin Demir

Carmen Mota Reyes

Elke Demir

Helmut Friess

Introduction

404

(1)

Individual Therapy Based on the Genomic and Transcriptomic Traits of Pancreatic Cancer

404

(1)

Organoids for Response Prediction

405

(1)

Enhancing the Activation of Immune Surveillance and Inhibition of Immune Suppression

406

(1)

Exploiting the Metabolic Alterations in Pancreatic Cancer Cells

406

(1)

Targeting the Tumor Stroma

407

(1)

Summary

407

(1)

References

407

(2)

51 New-onset Diabetes as a Harbinger of Pancreatic Cancer: is Early Diagnosis Possible?

409

(9)

Dana K. Andersen

Suresh T. Chari

Eithne Costello

Tatjana Crnogorac-Jurcevic

Phil A. Hart

Anirban Maitra

Stephen J. Pandol

Introduction

409

(1)

Epidemiology of DM in PDAC

409

(1)

Dual Causality of DM and PDAC

409

(1)

Evidence for NOD being a Paraneoplastic Process

410

(1)

Using NOD for Early Detection of PDAC

410

(2)

The Need for Early Detection of PDAC to Improve Overall Survival

410

(1)

Why NOD is the Leading Candidate for Early Detection

411

(1)

Challenges and Opportunities of Studying NOD: Finding the High-risk Cohort

411

(1)

Methods to Enrich the NOD Cohort to Screen for PDAC

412

(1)

The Role of T3cD and the Significance of New-onset T3cD

412

(1)

Statistical Modeling Using Clinical and Algorithmic Identification

412

(1)

Biomarkers of T3cD and PDAC-DM

413

(1)

T3cD Biomarker

413

(1)

PDAC-DM Biomarkers

413

(1)

Current Research Endeavors

413

(2)

The CPDPC NOD Study

413

(1)

The Cancer Research UK-funded UK Early Detection Initiative Study

414

(1)

The CPDPC DETECT Study

414

(1)

Commonalities of the Investigative Approaches in the United States and the UK

414

(1)

Challenges of Studying NOD Secondary to PDAC

414

(1)

Conclusions and Recommendations to Practitioners

415

(1)

Acknowledgments

415

(1)

References

415

(3)

52 Pancreatic Cancer Screening: Target Populations, Methods, and Protocols for Clinical Practice

418

(7)

Christopher Paiji

Anne Marie Lennon

Elham Afghani

Introduction

418

(1)

Target Populations

418

(2)

Germline Genetic Mutations Associated with Pancreatic Cancer

418

(1)

Peutz-Jeghers Syndrome

418

(1)

Hereditary Pancreatitis

418

(1)

Familial Atypical Multiple Mole Melanoma

418

(1)

Hereditary Breast and Ovarian Cancer

419

(1)

Lynch Syndrome

419

(1)

Ataxia Telangiectasia

419

(1)

Familial Pancreatic Cancer Families

419

(1)

Screening Modality

420

(1)

Imaging

420

(1)

Biomarkers

420

(1)

Screening Protocol

420

(1)

Who Should be Screened and When?

420

(1)

How Should you Screen?

421

(1)

Outcomes of Screening and Surveillance Programs

421

(1)

Cost-effectiveness of Pancreatic Cancer Screening Programs

422

(1)

Conclusion

422

(1)

Acknowledgments

422

(1)

References

422

(3)

53 Clinical Usefulness of Biological Markers in Pancreatic Cancer

425

(8)

David Anz

Ignazio Piseddu

Marlies Kopke

Ujjwal M. Mahajan

Julia Mayerle

Introduction

425

(1)

Challenges in Early Detection of Pancreatic Cancer

425

(1)

Role of Clinically Established Biomarkers of Pancreatic Cancer

426

(1)

Early Cancer Detection by Novel Biomarkers

426

(4)

Metabolomics

426

(1)

Circulating Tumor Cells

427

(1)

Cell-free DNA

427

(1)

Cell-free MicroRNA

428

(1)

Exosomes

428

(2)

Summary

430

(1)

References

430

(3)

54 Staging Classification and Stratification of Pancreatic Cancer for Clinical Practice

433

(10)

Akhil Chawla

Andrew J. Aguirre

Introduction

433

(1)

Clinical Staging

433

(1)

Additional Prognostic Factors

434

(1)

Clinically Relevant Molecular Features

434

(1)

Imaging Classification of Non-metastatic Disease

435

(2)

Imaging for Staging

437

(1)

Computed Tomography

437

(1)

Magnetic Resonance Imaging

437

(1)

Positron Emission Tomography

437

(1)

Endoscopic Ultrasound

437

(1)

Suggested Radiology Report Format

438

(1)

Evaluating Response to Neoadjuvant Therapy

438

(1)

Clinical Evaluation

438

(1)

Pathological Evaluation

438

(1)

Future Directions

439

(1)

Acknowledgments

439

(1)

References

439

(4)

55 Imaging Diagnosis and Staging of Pancreatic Cancer: Which Methods are Essential and What Information Should they Provide?

443

(6)

Megan H. Lee

Elliot K. Fishman

Introduction

443

(1)

CT Technique

443

(1)

Anatomy

443

(1)

Pancreatic Adenocarcinoma

444

(4)

Tumor Detection

444

(1)

Initial Staging

444

(1)

Local Invasion

445

(1)

Metastatic Disease

446

(1)

Postsurgical Imaging

447

(1)

Normal Postsurgical Appearance

447

(1)

Postsurgical Complications

448

(1)

Recurrent and Metastatic Disease

448

(1)

Conclusion

448

(1)

References

448

(1)

56 The Role of Endoscopic Ultrasound and Associated Methods (Elastography, Contrast Enhancement) in the Diagnosis and Assessment of Resectability of Pancreatic Cancer

449

(11)

Marc Giovannini

Introduction

449

(1)

Endoscopic Ultrasound for the Diagnosis and Staging of Pancreatic Cancer

449

(2)

Classification of Pancreatic Cancer According to EUS Findings

449

(1)

Role of EUS in the Diagnosis of Pancreatic Cancer

450

(1)

Accuracy of EUS Compared to Cross-sectional Imaging Techniques for the Assessment of Locoregional Extension of Pancreatic Cancer

450

(1)

Accuracy for T and N Staging

450

(1)

Evaluation of Vascular Involvement

450

(1)

Nodal Invasion

451

(1)

EUS-guided Fine Needle Biopsy

451

(1)

EUS Elastography

452

(1)

Theory and Technical Aspects of Elastography

452

(1)

Role of EUS Elastography in the Diagnosis of Pancreatic Cancer

452

(1)

Contrast-enhanced EUS

453

(3)

General Considerations

453

(1)

Commercially Available Ultrasound Contrast Agents in Europe

455

(1)

Role of Contrast-enhanced EUS in the Diagnosis of Pancreatic Cancer

456

(1)

Conclusion

456

(1)

References

456

(4)

57 EUS-Guided FNA/FNB for Pancreatic Solid Lesions: When is it Indicated and What is the Optimal Technical Approach?

460

(12)

Mihai Rimba

Gianenrico Rizzatti

Alberto Larghi

Introduction

460

(1)

Indications for Performing EUS-guided Tissue Acquisition

460

(2)

Optimal Technical Approach to EUS Tissue Acquisition

462

(2)

General Rules for Performing EUS-TA

464

(1)

EUS-guided Fine Needle Aspiration

464

(4)

Number of Passes

464

(1)

Needle Size

468

(1)

Use of Suction

468

(1)

Use of the Stylet

468

(1)

EUS-guided Fine Needle Biopsy

468

(1)

Conclusions

468

(1)

Acknowledgment

468

(1)

References

469

(3)

58 Surgical Treatment of Resectable Pancreatic Cancer: What is the Optimal Strategy?

472

(5)

Jan G. D'Haese

Bernhard W. Renz

Jens Werner

Introduction

472

(1)

Standard Resections and Lymphadenectomy for Resectable Pancreatic Cancer

472

(2)

Pancreaticoduodenectomy (Kausch-Whipple Procedure)

472

(1)

Pancreatic Left Resection

473

(1)

Minimally Invasive Surgery

474

(1)

Extended Resections

474

(1)

Future Perspectives

475

(1)

References

476

(1)

59 Complications After Pancreatic Surgery: How to Deal with Them?

477

(11)

Tommaso Giuliani

Giovanni Marchegiani

Giuseppe Malleo

Claudio Bassi

Introduction

477

(1)

Postoperative Pancreatic Fistula

477

(2)

Definition and Classification

477

(1)

Incidence and Risk Factors

477

(1)

Mitigation Strategies and Treatment

478

(1)

Post-pancreatectomy Hemorrhage

479

(1)

Delayed Gastric Emptying

480

(1)

Biliary Leakage

481

(1)

Chyle Leak

481

(2)

Enhanced Recovery After Surgery Policies and Centralization

483

(1)

Conclusion

483

(1)

References

484

(4)

60 Neoadjuvant Treatment of Pancreatic Cancer: When and How?

488

(13)

Matta Sandini

Thilo Hackett

Ulla Klaiber

Markus W. Buchler

John P. Neoptolemos

Background

488

(1)

What we have Learnt about Pancreatic Cancer from Adjuvant Therapy Trials

488

(1)

The Relevance of a Positive Resection Margin, Local Recurrence and Overall Survival

488

(1)

Neoadjuvant Therapy

489

(8)

Rationale for Neoadjuvant Chemotherapy

489

(1)

Resectable Pancreatic Cancer

489

(1)

Borderline Resectable and Locally Advanced Pancreatic Cancer

489

(1)

Guidelines for Neoadjuvant Therapy

489

(1)

Classification of Resectability

490

(1)

Neoadjuvant Trials in Resectable and Borderline Resectable Pancreatic Cancer

490

(1)

Neoadjuvant Trials in Borderline Resectable Pancreatic Cancer

490

(6)

Neoadjuvant Trials in Resectable and Borderline Pancreatic Cancer

496

(1)

Neoadjuvant Treatment for Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer

496

(1)

Surgical Approaches Following Neoadjuvant Treatment for Borderline and Unresectable Locally Advanced Pancreatic Cancer

497

(1)

Conclusions

497

(1)

References

498

(3)

61 Adjuvant Therapy in Pancreatic Cancer: Options, Safety, and Outcomes

501

(5)

Jean-Luc Van Laethem

Introduction

501

(1)

Brief History and Development of Adjuvant Therapy

501

(1)

Recent Phase III Trials Evaluating Combination Chemotherapy

502

(1)

Current Standards and Choices in Adjuvant Therapy

502

(2)

Future Perspectives

504

(1)

Summary

504

(1)

References

504

(2)

62 Management of Pain in Pancreatic Cancer: An Algorithm for Clinical Routine

506

(8)

J. Enrique Dominguez-Munoz

Relevance of Abdominal Pain in Pancreatic Cancer

506

(1)

Approach to Pain Management in Pancreatic Cancer

506

(2)

Pain Assessment

506

(1)

What is the Most Likely Cause of Pain?

507

(1)

Cancer Treatment

507

(1)

Psychological Support

507

(1)

Nutritional Management and Treatment of Pancreatic Exocrine Insufficiency

508

(1)

Pain Therapy in Pancreatic Cancer

508

(3)

Pharmacological Therapy

508

(1)

Interventional Neurolytic Methods

509

(1)

Other Therapies

510

(1)

Management of Pain in Pancreatic Cancer: An Algorithm for Clinical Routine

511

(1)

References

512

(2)

63 EUS-guided Celiac Plexus Neurolysis for Pain in Pancreatic Cancer: When and How?

514

(6)

Jonathan M. Wyse

Anand V. Sahai

Introduction

514

(1)

When EUS-CPN Should be Considered

514

(1)

Safety of EUS-CPN

515

(1)

Celiac Ganglia Neurolysis

516

(1)

How to Inject and What to Expect: Unilateral vs. Bilateral Injection

516

(1)

Is the Future of EUS-CPN Neurolysis with a Different Neurolytic?

517

(1)

Summary

517

(1)

References

518

(2)

64 The Role of Endoscopy in the Management of Unresectable Pancreatic Cancer

520

(10)

Jaimin P. Amin

Ajaypal Singh

Irving Waxman

Background

520

(1)

Malignant Biliary Obstruction

520

(4)

Newer Advances in Endoscopic Palliation of Biliary Obstruction

523

(1)

Intraductal Radiofrequency Ablation

523

(1)

EUS-guided Biliary Access and Drainage

523

(1)

Gastroduodenal Outlet Obstruction

524

(3)

EUS-guided Gastrojejunostomy

526

(1)

Tumor-related Bleeding

527

(1)

The Future

527

(1)

Conclusions

527

(1)

References

528

(2)

65 Chemotherapy for Nonresectable Pancreatic Cancer

530

(8)

Raquel Fuentes

Juan Jose Serrano

Mercedes Rodriguez

Alfredo Carrato

Introduction

530

(1)

First Line

530

(2)

Single-agent Chemotherapy

530

(1)

Gemcitabine

530

(1)

Oral Fluoropyrimidines: Capecitabine and S-1

531

(1)

Fluorouracil-based Combination Regimens

531

(1)

Gemcitabine Combinations

531

(1)

Gemcitabine plus Nab-paclitaxel

531

(1)

Gemcitabine plus Capecitabine or S-1

532

(1)

Gemcitabine plus Erlotinib and Other Molecularly Targeted Agents

532

(1)

Second Line

532

(1)

After First-line Gemcitabine

532

(1)

Liposomal Irinotecan (MM-398, Onivyde)

532

(1)

Irinotecan

533

(1)

Oxaliplatin-based Regimens

533

(1)

Other Oxaliplatin-based Regimens

533

(1)

Other Regimens

533

(1)

After First-line FOLFIRINOX

533

(1)

Genetic Testing

533

(1)

Deficient Mismatch Repair/High Level of Microsatellite Instability

534

(1)

BRCA Mutation Carriers

534

(1)

Conclusions

534

(1)

References

535

(3)

66 Diagnosis and Management of Pancreatic Exocrine Insufficiency in Pancreatic Cancer

538

(10)

Sarah Powell-Brett

Keith J. Roberts

Mechanisms of Pancreatic Exocrine Insufficiency in Pancreatic Cancer

538

(2)

PEI in Irresectable Pancreatic Cancer

538

(1)

PEI in Resectable Pancreatic Cancer

538

(2)

Symptoms of PEI

540

(1)

Diagnosis of PEI in Pancreatic Cancer

541

(1)

Treatment of PEI with PERT

542

(3)

Treatment Dosing

542

(1)

Gastric Barrier: pH and Gastric Emptying

542

(1)

PERT in Pancreatic Cancer

543

(1)

PERT in Unresectable Pancreatic Cancer

543

(1)

PERT in Resectable Pancreatic Cancer

543

(1)

Overall Survival and Quality of Life Benefit of PERT in Pancreatic Cancer

544

(1)

Undertreatment of PEI

544

(1)

Key Recommendations

545

(1)

References

545

(3)

67 Nutrition and Pancreatic Cancer

548

(7)

Mary Phillips

Oonagh Griffin

Introduction

548

(1)

Impact of Pancreatic Ductal Adenocarcinoma on Nutrient Metabolism

548

(1)

Pancreatic Exocrine Insufficiency

548

(1)

Cancer Cachexia and PDAC

549

(1)

Treatment Strategies for Malnutrition in Pancreatic Cancer

549

(3)

Locally Advanced and/or Metastatic Disease

549

(1)

Resectable Pancreatic Cancer

550

(1)

Preoperative Considerations

550

(1)

Postoperative Nutritional Support

550

(1)

Post-discharge Nutrition

551

(1)

Survivorship

551

(1)

Conclusion

552

(1)

References

552

(3)

68 Present and Future of Local Therapies for Unresectable Pancreatic Cancer

555

(9)

Sabrina Gloria Giulia Testoni

Gemma Rossi

Livia Archibugi

Paolo Giorgio Arcidiacono

Introduction

555

(1)

Direct Antitumor Therapy

555

(4)

EUS-guided Radiofrequency Ablation

555

(2)

EUS-guided Irreversible Electroporation

557

(1)

EUS-guided Nd:YAG Laser Ablation

557

(1)

EUS-guided Photodynamic Therapy

557

(1)

EUS-guided High-intensity Focused Ultrasound

558

(1)

EUS-guided HybridTherm Ablation

558

(1)

Indirect Antitumor Therapy

559

(2)

EUS-guided Fiducial Placement

559

(1)

EUS-guided Brachytherapy

560

(1)

EUS-guided Fine-needle Antitumor Injection

560

(1)

Future Directions

561

(1)

References

561

(3)

69 New Pharmacological Approaches for Pancreatic Cancer Therapy: A Light at the End of the Tunnel?

564

(9)

Vineet K. Gupta

Sulagna Banerjee

Ashok K. Saluja

Introduction

564

(1)

Pancreatic Cancer: Challenges in the Field

564

(2)

Tumor Heterogeneity

564

(1)

Desmoplasia in the Tumor

565

(1)

Late Detection of Disease

566

(1)

Surgical Challenges

566

(1)

Overcoming Challenges: Therapy against Pancreatic Cancer

566

(3)

Targeting EGF

566

(1)

Targeting Heat-shock Proteins

567

(1)

Antistromal Therapy

567

(1)

Immunotherapy

568

(1)

Metabolic Inhibitors

568

(1)

Conclusion

569

(1)

Acknowledgments

569

(1)

Disclosures

569

(1)

References

569

(4)

Section VI Cystic Tumors of the Pancreas

573

(58)

70 Histological Classification of Pancreatic Cystic Neoplasms

575

(9)

Giuseppe Zamboni

Anna Pesci

Introduction

575

(1)

Serous Cystic Neoplasm

575

(1)

Mucinous Cystic Neoplasm

576

(1)

Intraductal Papillary Mucinous Neoplasm

577

(2)

Intraductal Oncocytic Papillary Neoplasm

579

(1)

Intraductal Tubulopapillary Neoplasm

579

(1)

Solid Pseudopapillary Neoplasm

580

(1)

References

581

(3)

71 Role of Endoscopic Ultrasound and Endoscopic Ultrasound-associated Techniques in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Tumors

584

(9)

Maria-Victoria Alvarez-Sanchez

Bertrand Napoleon

Introduction

584

(1)

EUS Imaging

584

(1)

EUS-FNA

585

(2)

Cytology

585

(1)

Cyst Fluid Analysis

586

(1)

Molecular Biomarkers

586

(1)

EUS-guided Through-the-needle Imaging

587

(1)

Cystoscopy

587

(1)

Needle-based Confocal Laser Endomicroscopy

587

(1)

EUS-guided Through-the-needle Biopsy

588

(1)

Summary

589

(1)

References

590

(3)

72 The Role of Multidetector CT, MRI and MRCP in the Diagnosis and Differential Diagnosis of Pancreatic Cystic Neoplasms

593

(6)

Megan H. Lee

Elliot K. Fishman

Introduction

593

(1)

CT Technique

593

(1)

MRI Technique

593

(1)

Cystic Pancreatic Masses

593

(3)

Mucinous Cystic Neoplasms

594

(1)

Serous Cystadenomas

594

(1)

Intraductal Papillary Mucinous Neoplasms

595

(1)

Other Cystic Pancreatic Lesions

596

(1)

Solid Pseudopapillary Tumor

596

(1)

Lymphoepithelial Cysts

596

(1)

Neuroendocrine Tumors

597

(1)

Conclusion

597

(1)

References

598

(1)

73 Intraductal Papillary Mucinous Neoplasm: When to Observe, When to Operate, and Optimal Surgical Approach

599

(9)

Zhi Ven Fong

Carlos Fernandez-del Castillo

Introduction

599

(1)

Clinical Considerations

599

(2)

Clinical History

599

(1)

Radiographic Features

600

(1)

Pancreatic Cyst Fluid Analysis

600

(1)

IPMN Guidelines

601

(1)

International Association of Pancreatology Sendai Guidelines

601

(1)

American Gastroenterological Association Guidelines

601

(1)

European Evidence-based Guidelines

601

(1)

Reconciling the Differences

602

(2)

Surveillance Strategy for IPMNS not Meeting Criteria for Resection

604

(1)

Optimal Surgical Approach

604

(1)

Long-term Follow-up after Surgical Resection

604

(1)

Conclusions

605

(1)

References

605

(3)

74 Cystic Tumors Other than IPMN: When to Observe, When to Operate, and Optimal Surgical Approach

608

(16)

John W. Kunstman

James J. Farrell

Introduction

608

(1)

Scope of Pancreatic Cystic Neoplasia

608

(1)

Mucinous Cystic Neoplasm

609

(2)

Indications for Surgery

609

(2)

Approach to Management

611

(1)

Serous Cystic Neoplasm

611

(3)

Indications for Surgery

612

(1)

Approach to Management

613

(1)

Solid Pseudopapillary Neoplasm

614

(2)

Indications for Surgery

615

(1)

Approach to Management

616

(1)

Cystic Pancreatic Endocrine Neoplasm

616

(1)

Indication for Surgery

617

(1)

Approach to Management

617

(1)

Other Rare Cystic Neoplasms

617

(2)

Lymphoepithelial Cysts

617

(1)

Cystic Lymphangioma

618

(1)

Cystic Degeneration of Solid Tumors

618

(1)

References

619

(5)

75 Pancreatic Cystic Tumors: any Role for Local Therapies?

624

(7)

Julio Iglesias-Garcia

Introduction

624

(1)

Indications for EUS-guided Ablation Therapy

624

(1)

Cystic Pancreatic Tumors

625

(1)

EUS-guided Therapy

625

(3)

Radiofrequency Ablation

625

(1)

Alcohol and/or Chemical Ablation

626

(2)

Conclusions

628

(1)

References

628

(3)

Section VII Neuroendocrine and Other Tumors of the Pancreas

631

(20)

76 Diagnosis and Treatment of Pancreatic Neuroendocrine Tumors: How to Deal with them in Clinical Practice?

633

(8)

Francesca Muffatti

Stefano Partelli

Valentina Andreasi

Massimo Falconi

Introduction

633

(1)

Clinical Presentation

633

(2)

Diagnosis

635

(1)

Laboratory

635

(1)

Imaging

635

(1)

Morphological Imaging

635

(1)

Functional Imaging

635

(1)

Staging Systems

636

(1)

Treatment

637

(1)

F-PanNENs

637

(1)

Nonfunctioning PanNENs

637

(1)

Localized Disease

637

(1)

Metastatic Disease

637

(1)

Acknowledgments

638

(1)

References

639

(2)

77 Other less Frequent Pancreatic Tumors: What Should be Known about Clinical Features, Diagnosis and Treatment?

641

(10)

Rossana Percario

Paolo Panaccio

Fabio F. di Mola

Pierluigi Di Sebastiano

Tommaso Grottola

Acinar Cell Carcinoma of Pancreas

641

(1)

Definition and Epidemiology

641

(1)

Clinical Symptoms

641

(1)

Diagnosis

641

(1)

Laboratory

641

(1)

Radiology

641

(1)

Fine-needle Aspiration

641

(1)

Treatment

642

(1)

Hepatoid Carcinoma of Pancreas

642

(1)

Schwannoma of Pancreas

642

(1)

Perivascular Epithelial Cell Tumor of Pancreas

642

(1)

Hematological Malignancies of Pancreas

643

(1)

Non-Hodgkin Lymphoma of the Pancreas

643

(1)

Post-transplantation Lymphoproliferative Disorder

643

(1)

Granulocytic Sarcoma

643

(1)

Multiple Myeloma and Solitary Plasmacytoma

643

(1)

Castleman Disease

644

(1)

Primary Leiomyoma of Pancreas

644

(1)

Primary Leiomyosarcoma of Pancreas

644

(1)

Pancreatic Lipoma

644

(1)

Pancreatic Liposarcoma

644

(1)

Cystic Lymphangioma of Pancreas

645

(1)

Squamous-lined Cyst of Pancreas

645

(1)

Lymphoepithelial Cyst

645

(1)

Epidermoid Cyst

645

(1)

Dermoid Cyst or Mature Cystic Teratoma

645

(1)

Solid Papillary Neoplasm

646

(1)

Adult Pancreatoblastoma

646

(1)

Pancreatic Metastasis from Other Tumors

646

(1)

Renal Cell Cancer Metastasis

646

(1)

Colorectal Cancer Metastasis

646

(1)

Melanoma Metastasis

646

(1)

Breast Cancer Metastasis

647

(1)

Lung Cancer Metastasis

647

(1)

Sarcoma Metastasis

647

(1)

References

647

(4)

Section VIII Functional Alterations of the Pancreas in Other Clinical Situations

651

(28)

78 Diagnosis and Therapy of Exocrine Pancreatic Insufficiency after Gastric and Pancreatic Surgery

653

(9)

Raffaele Pezzilli

Introduction

653

(1)

Gastrectomy

653

(3)

Pathophysiology of EPI

653

(1)

How to Assess Pancreatic Function in Gastrectomized Patients

654

(1)

Pancreatic Enzyme Replacement Therapy after Gastric Resection

655

(1)

Well-being of Gastrectomized Patients with Maldigestion

656

(1)

Future Perspectives

656

(1)

Pancreatectomy

656

(3)

Pathophysiology of EPI

656

(1)

How to Assess Pancreatic Function in Pancreatic-resected Patients

657

(1)

Pancreatic Enzyme Replacement Therapy after Pancreatic Resection

657

(1)

Well-being of Pancreatic-resected Patients with Maldigestion

658

(1)

Pancreatic Neoplasm

658

(1)

Chronic Pancreatitis

658

(1)

Type of Surgery and Reconstruction

659

(1)

Future Perspectives

659

(1)

References

659

(3)

79 Pancreatic Exocrine Insufficiency in Type 1 and Type 2 Diabetes Mellitus: Lessons from Pancreatologists to Diabetologists

662

(6)

Philip D. Hardt

Historical Aspects of Pancreatic Diseases and Diabetes Mellitus

662

(1)

Pancreatic Exocrine Function in Patients with Diabetes Mellitus

663

(1)

Pancreas Morphology in Patients with Diabetes Mellitus

663

(1)

Pathophysiological Concepts of Altered Exocrine Pancreas Morphology and Function in Type 1 and Type 2 Diabetes Mellitus

664

(1)

Exocrine Pancreatic Pathology as a Consequence of Diabetes Mellitus

664

(1)

Exocrine Changes in Type 1 Diabetes Mellitus

664

(1)

Exocrine Changes in Type 2 Diabetes Mellitus

664

(1)

Exocrine and Endocrine Pathology Caused by one Underlying Disease Process

664

(1)

Clinical Impact of Exocrine Disease in Type 1 and Type 2 Diabetes Mellitus

665

(1)

Conclusion

665

(1)

References

666

(2)

80 Diabetes Mellitus Related to :Diseases of the Exocrine Pancreas (Pancreatogenic Diabetes): Diagnosis and Treatment

668

(11)

David A. Bradley

Phil A. Hart

Introduction

668

(1)

Epidemiology

668

(2)

Chronic Pancreatitis-related Diabetes Mellitus

669

(1)

Post-pancreatectomy Diabetes Mellitus

669

(1)

Acute Pancreatitis-related Diabetes Mellitus

670

(1)

Cystic Fibrosis-related Diabetes Mellitus

670

(1)

Diagnosis

670

(1)

Treatment

671

(3)

Chronic Pancreatitis-related Diabetes Mellitus

671

(2)

Acute Pancreatitis-related Diabetes Mellitus

673

(1)

Pancreatic Ductal Adenocarcinoma-related Diabetes Mellitus

673

(1)

Cystic Fibrosis-related Diabetes

673

(1)

Knowledge Gaps

674

(1)

Conclusions

674

(1)

Acknowledgments

675

(1)

References

675

(4)

Index

679

About the editor

Prof. J. Enrique Domķnguez-Muńoz graduated in medicine from the University of Alcalį de Henares in Madrid, and got his PhD at the same University in 1990. In 1998, he became Director of the Department of Gastroenterology and Hepatology at the University Hospital of Santiago de Compostela, Spain. He is also Professor of Medicine at the University of Santiago de Compostela and permanent member of the Royal Academy of Medicine of Galicia. He has published more than 300 papers in peer reviewed journals, and has edited 12 books. He has been elected President of the European Pancreatic Club for 2024.

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