Clinical Pancreatology for Practising

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(May 24,
2021)_(1119570077)_(Wiley-Blackwell)
Juan Enrique Dominguez Muñoz
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Clinical Pancreatology for Practising Gastroenterologists
and Surgeons
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
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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
 v

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
vi Contents

I­ nvestigative 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 vii

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
viii Contents

­ ocal Anesthetics 69
L
­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 ix

Endoscopic or Laparoscopic Necrosectomy 102

­ eferences 102
R

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
x Contents

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 xi

­ acroenzymemia 161
M
­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
xii Contents

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
I­ ntroduction 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 xiii

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
xiv Contents

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 xv

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
xvi Contents

­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 xvii

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
xviii Contents

­ ostprocedure Care 319

P
­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 xix

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
xx Contents

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 xxi

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
xxii Contents

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
Additional Prognostic Factors 434
 Contents xxiii

­ linically Relevant Molecular Features 434

C
­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
xxiv Contents

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 xxv

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
xxvi Contents

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 xxvii

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
xxviii Contents

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 xxix

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
xxx Contents

­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 xxxi

Lung Cancer Metastasis 647

Sarcoma Metastasis 647
­ eferences 647
R

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
xxxii Contents

Acute Pancreatitis-related Diabetes Mellitus 670

Cystic Fibrosis-related Diabetes Mellitus 670
­Diagnosis 670
­Treatment 671
Chronic Pancreatitis-related Diabetes Mellitus 671
Acute Pancreatitis-related Diabetes Mellitus 673
Pancreatic Ductal Adenocarcinoma-related Diabetes Mellitus 673
Cystic Fibrosis-related Diabetes 673
­Knowledge Gaps 674
­Conclusions 674
Acknowledgments 675
­References 675

Index 679
 xxxiii

Contributors

Elham Afghani, MD, MPH Jaimin P. Amin, MD, MS

Assistant Professor of Medicine
Division of Gastroenterology, and Pancreatitis
Center
Johns Hopkins Medical Institutions
Baltimore, MD, USA
Assistant Professor of Medicine
Digestive Diseases and Interventional Gastroenterology
Rush University Medical Center – University
Gastroenterologists
Chicago, IL, USA

Anil K. Agarwal, MS, MCh, FRCS, FACS Antonio Amodio, MD

Director Professor and Head Department of Medicine
Department of Gastrointestinal Surgery and Liver Pancreas Center
Transplant University of Verona
Govind Ballabh Pant Hospital and Maulana Azad Verona, Italy
Medical College, Delhi University
New Delhi, India Dana K. Andersen, MD
Scientific Program Manager, Division of Digestive
Andrew J. Aguirre, MD, PhD Diseases and Nutrition
Broad Institute of MIT and Harvard, Cambridge; National Institute of Diabetes and Digestive and
Department of Medical Oncology, Dana-Farber Kidney Diseases
Cancer Institute; National Institutes of Health
Department of Medicine, Brigham and Women’s Bethesda, MD, USA
Hospital and Harvard Medical School
Boston, MA, USA Valentina Andreasi, MD
Pancreas Translational and Clinical Research Center
Fatih Akisik, MD Pancreatic Surgery IRRCS San Raffaele Hospital
Professor Vita-Salute San Raffaele University
Department of Radiology and Imaging Sciences Milan, Italy
Indiana University School of Medicine
Indianapolis, IN, USA Trine Andresen, MSc (Pharm), PhD
Centre for Pancreatic Diseases and Mech-Sense
María-Victoria Alvarez-Sánchez, MD Department of Gastroenterology and Hepatology,
Complejo Hospitalario Universitario de Pontevedra Aalborg University Hospital
Instituto de Investigación Sanitaria Galicia Sur Department of Clinical Medicine, Aalborg University
Pontevedra, Spain Aalborg, Denmark
xxxiv Contributors

David Anz, MD Jamie S. Barkin, MD, MACP, MACG, AGAF, FASGE

Department of Medicine II Department of Medicine, Division of
University Hospital Gastroenterology
Ludwig-Maximilians-Universität München Leonard M. Miller School of Medicine, University of
Munich, Germany Miami, Miami, FL, USA

Minoti V. Apte, MBBS, M Med Sci, PhD, FAAHMS Jodie A. Barkin, MD

Pancreatic Research Group, South Western Sydney Department of Medicine, Division of
Clinical School Gastroenterology
Faculty of Medicine, UNSW Sydney, Sydney; Leonard M. Miller School of Medicine, University of
Ingham Institute for Applied Medical Research Miami
Liverpool, New South Wales, Australia Miami, FL, USA

Livia Archibugi, MD Jahangeer Basha, MD

Pancreas Translational and Clinical Research Center
Division of Pancreato-Biliary Endoscopy and
Endosonography
San Raffaele Scientific Institute
Vita-Salute San Raffaele University
Milan, Italy
Paolo Giorgio Arcidiacono, MD, FASGE
Pancreas Translational and Clinical Research Center
Division of Pancreato-Biliary Endoscopy and
Endosonography
IRCCS San Raffaele Scientific Institute
Vita-Salute San Raffaele University
Milan, Italy
Muhammad Awais, PhD
Liverpool Pancreatitis Research Group
Institute of Translational Medicine
University of Liverpool
Liverpool, UK
Sandra Baleato-González, MD, PhD
Department of Radiology
Hospital Clínico Universitario de Santiago de
Compostela
Santiago de Compostela, Spain
Sulagna Banerjee, PhD
Sylvester Comprehensive Cancer Center
DeWitt Daughtry Family Department of Surgery,
University of Miami
Miami, FL, USA
Peter A. Banks, MD
Harvard Medical School
Boston, MA, USA
Asian Institute of Gastroenterology Hospitals
Hyderabad, India
Claudio Bassi, MD, FRCS, FACS
Department of Surgery
Pancreas Institute of the Verona University
Hospital
Verona, Italy
Ivo Boškoski, MD, PhD
Digestive Endoscopy Unit, Fondazione Policlinico
Universitario Agostino Gemelli IRCSS
Università Cattolica del Sacro Cuore di Roma,
Center for Endoscopic Research Therapeutics and
Training (CERTT)
Rome, Italy
David A. Bradley, MD
Diabetes & Metabolism Research Center
Division of Endocrinology, Diabetes, and
Metabolism
The Ohio State University Wexner Medical Center
Columbus, OH, USA
Jefferson N. Brownell, MD
Instructor in Pediatrics
Division of Gastroenterology, Hepatology, and
Nutrition
Children’s Hospital of Philadelphia
Department of Pediatrics, University of
Pennsylvania Perelman School of Medicine,
Philadelphia, PA, USA
Marco J. Bruno, MD, PhD
Department of Gastroenterology and Hepatology
Erasmus MC University Medical Center
Rotterdam, the Netherlands
 Contributors xxxv

Markus W. Büchler, MD, FACS Mayo Clinic

Department of General, Visceral and Rochester, MN, USA
Transplantation Surgery
University of Heidelberg Akhil Chawla, MD
Heidelberg, Germany Division of Surgical Oncology, Department of
Surgery
Fernando Burdío, MD, PhD Northwestern Medicine Regional Medical Group
Department of Surgery, Hospital del Mar Northwestern University Feinberg School of
Universidad Autónoma de Barcelona Medicine
Barcelona, Spain Chicago, IL, USA
Djuna L. Cahen, MD, PhD
Department of Gastroenterology and Hepatology Darwin L. Conwell, MD, MS
Erasmus MC University Medical Center Professor and Director
Rotterdam, the Netherlands Division of Gastroenterology, Hepatology and
Nutrition
Wenhao Cai, PhD student Floyd Beman Endowed Chair in Gastroenterology
Liverpool Pancreatitis Research Group Co-Director, Digestive Disease Area of
Institute of Translational Medicine Concentration
University of Liverpool Ohio State University Wexner Medical Center
Liverpool, UK Columbus, OH, USA
and Department of Integrated Traditional Chinese
Medicine and Western Medicine Guido Costamagna, MD, PhD
West China Hospital, Digestive Endoscopy Unit, Fondazione Policlinico
Chengdu, China Universitario Agostino Gemelli IRCSS
Università Cattolica del Sacro Cuore di Roma,
Gabriele Capurso, MD, PhD, AGAF Center for Endoscopic Research Therapeutics and
Pancreas Translational and Clinical Research Training
Center (CERTT)
Division of Pancreato-Biliary Endoscopy and Rome, Italy
Endosonography
IRCCS San Raffaele Scientific Institute Eithne Costello, PhD
Milan, Italy Professor of Molecular and Clinical Cancer
Medicine
Alfredo Carrato, MD, PhD Institute of Translational Medicine
Medical Oncology Department, University of Liverpool
Ramon y Cajal University Hospital; Liverpool, UK
Alcala University
Madrid, Spain Tatjana Crnogorac-Jurcevic, MD, PhD
Professor of Molecular Oncology
Ricardo Arvizu Castillo, MD Barts Cancer Institute
Liver, Biliary and Pancreatic Unit Queen Mary University of London
Department of General Surgery London, UK
Hospital Clínico, University of Valencia
Biomedical Research Institute INCLIVA László Czakó, MD, PhD, DSc, MSc
Valencia, Spain Professor
President of the Hungarian Pancreatic Club
Suresh T. Chari, MD Council member of the European Pancreatic Club
Professor of Medicine First Department of Medicine, University of Szeged
Division of Gastroenterology and Hepatology Szeged, Hungary
xxxvi Contributors

Jan G. D’Haese, MD Mahya Faghih, MD

Associate Professor of Surgery Division of Gastroenterology
Attending Surgeon Johns Hopkins Medical Institutions
Department of General, Visceral, and Transplantation Baltimore, MD, USA
Surgery
Ludwig Maximilian University Hospital Massimo Falconi, MD
Munich, Germany Pancreas Translational and Clinical Research
Center
Muhammad F. Dawwas, MBChB Pancreatic Surgery IRRCS San Raffaele Hospital
Jewish Hospital and St. Mary’s HealthCare Vita-Salute San Raffaele University
Louisville, KY, USA Milan, Italy

Elke Demir, MD James J. Farrell, MD

Department of Surgery, Klinikum rechts der Isar Director, Yale Pancreatic Disease Program
Technical University of Munich, School of Medicine Interventional Endoscopy and Pancreatic Disease
Munich, Germany Yale University School of Medicine
New Haven, CT, USA
Ihsan Ekin Demir, MD, PhD
Department of Surgery, Klinikum rechts der Isar
Carlos Fernandez-del Castillo, MD
Technical University of Munich, School of Medicine
Department of Surgery
Munich, Germany
Massachusetts General Hospital
Harvard Medical School
Matthew J. DiMagno, MD
Boston, MA, USA
Associate Professor of Medicine
Director, Comprehensive Pancreas Program
Elliot K. Fishman, MD
Gastroenterology Director, Adult CF Program
Russell H. Morgan Department of Radiology and
Department of Internal Medicine
Radiological Science
Division of Gastroenterology and Hepatology
Johns Hopkins University School of Medicine
University of Michigan School of Medicine
Baltimore, MD, USA
Ann Arbor, MI, USA

Pierluigi Di Sebastiano, MD, FACS Zhi Ven Fong, MD, MPH

Surgical Oncology Unit Department of Surgery
G. D’Annunzio University Massachusetts General Hospital
Pierangeli Clinic Harvard Medical School
Pescara, Italy Boston, MA, USA

J. Enrique Domínguez-Muñoz, MD, PhD Chris E. Forsmark, MD

Department of Gastroenterology and Hepatology Professor of Medicine and Chief
University Hospital of Santiago de Compostela Division of Gastroenterology, Hepatology, and
Santiago de Compostela, Spain Nutrition
University Term Professor
Asbjørn Mohr Drewes, MD, PhD, DMSc University of Florida
Centre for Pancreatic Diseases and Mech-Sense Gainesville, FL, USA
Department of Gastroenterology and Hepatology,
Aalborg University Hospital Helmut Friess, MD
Department of Clinical Medicine, Aalborg Department of Surgery, Klinikum rechts der Isar
University Technical University of Munich, School of Medicine
Aalborg, Denmark Munich, Germany
 Contributors xxxvii

Luca Frulloni, MD, PhD, AGAF Oonagh Griffin, BSc (Hons), RD

Department of Medicine HRB Research Fellow and Senior Dietitian
Pancreas Center Pancreatic Cancer Care
University of Verona Trinity College Dublin and St Vincent’s University
Verona, Italy Hospital
Dublin, Ireland
Raquel Fuentes, MD
Medical Oncology Department Tommaso Grottola, MD
Ramon y Cajal University Hospital Surgical Oncology Unit
Madrid, Spain G. D’Annunzio University
Pierangeli Clinic
Roberto García-Figueiras, MD, PhD Pescara, Italy
Department of Radiology
Hospital Clínico Universitario de Santiago de Vineet K. Gupta, PhD
Compostela Sylvester Comprehensive Cancer Center
Santiago de Compostela, Spain DeWitt Daughtry Family Department of Surgery,
University of Miami
Timothy B. Gardner, MD, MS Miami, FL, USA
Section of Gastroenterology and Hepatology
Thilo Hackert, MD
Dartmouth-Hitchcock Medical Center
Department of General, Visceral and Transplantation
Lebanon, NH, USA
Surgery
University of Heidelberg
Pramod Kumar Garg, MD, DM
Heidelberg, Germany
Department of Gastroenterology
All India Institute of Medical Sciences Philip D. Hardt, MD, PhD
New Delhi, India Department of Gastroenterology
University Hospital Giessen
Sushil Kumar Garg, MBBS Giessen, Germany
Division of Gastroenterology and Hepatology
Mayo Clinic Phil A. Hart, MD
Rochester, MN, USA Associate Professor of Medicine
Division of Gastroenterology, Hepatology and
Andres Gelrud, MD, MMSc Nutrition
GastroHealth and Miami Cancer Institute Ohio State University Wexner Medical Center
Miami, FL, USA Columbus, OH, USA

Marc Giovannini, MD Wei Huang

Endoscopy Unit Liverpool Pancreatitis Research Group
Institut Paoli-Calmettes Institute of Translational Medicine
Marseille, France University of Liverpool
Liverpool, UK
Tommaso Giuliani, MD and Department of Integrated Traditional Chinese
Department of Surgery Medicine and Western Medicine
Pancreas Institute of the Verona University Hospital West China Hospital,
Verona, Italy Chengdu, China
xxxviii Contributors

Daniel de la Iglesia-García, MD University of Heidelberg

Department of Gastroenterology and Hepatology Heidelberg, Germany
University Hospital of Santiago de Compostela
Santiago de Compostela, Spain Marlies Köpke
Department of Medicine II
Julio Iglesias-Garcia, MD, PhD University Hospital
Department of Gastroenterology and Hepatology Ludwig-Maximilians-Universität München
Health Research Institute Munich, Germany
University Hospital of Santiago de Compostela
Santiago de Compostela, Spain
Louise Kuhlman, MD
Soumya Jagannath, MD, DM Centre for Pancreatic Diseases and Mech-Sense
Department of Gastroenterology Department of Gastroenterology and Hepatology,
All India Institute of Medical Sciences Aalborg University Hospital
New Delhi, India Department of Clinical Medicine, Aalborg
University
Amit Javed, MS, MCh Aalborg, Denmark
Department of Gastrointestinal Surgery and Liver
Transplant John W. Kunstman, MD, MHS
Govind Ballabh Pant Hospital and Maulana Azad Department of Surgery, Section of Surgical Oncology
Medical College, Delhi University Yale University School of Medicine, New Haven
New Delhi, India VA Connecticut Health System, Department of
Veterans Affairs
David X. Jin, MD, MPH West Haven, CT, USA
Associate Physician in Gastroenterology, Brigham
and Women’s Hospital Felix Lämmerhirt, MD
Instructor of Medicine, Harvard Medical School Department of Medicine A
Boston, MA, USA University Medicine Greifswald
Greifswald, Germany
Colin D. Johnson, MChir, FRCS
Emeritus Professor of Surgical Sciences
Luis F. Lara, MD
University Surgical Unit
Associate Professor of Clinical Medicine
University Hospitals Southampton
Medical Director of the Total Pancreatectomy and
Southampton, UK
Islet Cell Transplant Program
Division of Gastroenterology, Hepatology and
Pieter J. F. de Jonge, MD, PhD
Nutrition
Department of Gastroenterology and Hepatology
Ohio State University Wexner Medical Center
Erasmus MC University Medical Center
Columbus, OH, USA
Rotterdam, the Netherlands

Raja Kalayarasan, MS, MCh Alberto Larghi, MD, PhD

Department of Gastrointestinal Surgery and Liver
Transplant
Govind Ballabh Pant Hospital and Maulana Azad
Medical College, Delhi University
New Delhi, India
Ulla Klaiber, MD
Department of General, Visceral and
Transplantation Surgery
Digestive Endoscopy Unit
Fondazione Policlinico Universitario A. Gemelli
IRCCS
Rome, Italy
José Lariño-Noia, MD, PhD
Department of Gastroenterology and Hepatology
University Hospital of Santiago de Compostela
Santiago de Compostela, Spain
 Contributors xxxix

Megan H. Lee, MD Jorge D. Machicado, MD

Russell H. Morgan Department of Radiology and Division of Gastroenterology and Hepatology
Radiological Science Mayo Clinic Health System
Johns Hopkins University School of Medicine Eau Claire, WI, USA
Baltimore, MD, USA
Julia McNabb-Baltar, MD, MPH
Peter J. Lee, MBChB Harvard Medical School
Division of Gastroenterology and Hepatology Boston, MA, USA
Department of Medicine
Hospital of the University of Pennsylvania Enrique de Madaria, MD, PhD
Philadelphia, PA, USA Gastroenterology Department, Alicante University
General Hospital
Anne Marie Lennon, MD, PhD Alicante Institute for Health and Biomedical
Professor of Medicine Research (ISABIAL)
Johns Hopkins University Alicante, Spain
Baltimore, MD, USA
Ujjwal M. Mahajan, PhD
Department of Medicine II
Markus M. Lerch, MD, FRCP
University Hospital
Department of Medicine A
Ludwig-Maximilians-Universität München
University Medicine Greifswald
Munich, Germany
Greifswald, Germany
Patrick Maisonneuve, Dipl. Eng.
Philippe Lévy, MD, PhD Director, Unit of Clinical Epidemiology
Pancreatology Department, Beaujon Hospital Division of Epidemiology and Biostatistics
Assistance Publique – Hôpitaux de Paris Clichy IEO European Institute of Oncology IRCCS
Paris Diderot University Milan, Italy
Paris, France
Anirban Maitra, MBBS
J. -Matthias Löhr, MD, PhD
Professor and Scientific Director
Professor and Senior Consultant
Sheikh Ahmed Center for Pancreatic Cancer
Department for Digestive Diseases, Karolinska
Research
University Hospital
University of Texas MD Anderson Cancer Center
Department of Clinical Science, Intervention, and
Houston, TX, USA
Technology (CLINTEC), Karolinska Institutet
Stockholm, Sweden
Giuseppe Malleo, MD, PhD
Benjamin P.T. Loveday, MBChB, PhD, FRACS Department of Surgery
Department of Surgery, University of Auckland, Pancreas Institute of the Verona University Hospital
Auckland, New Zealand Verona, Italy
Department of Surgery, Royal Melbourne Hospital
Department of Surgical Oncology, Peter MacCallum Asim Maqbool, MD
Cancer Centre Associate Professor of Clinical Pediatrics
Melbourne, Australia Division of Gastroenterology, Hepatology, and
Nutrition
Daniel G. McCall, MD Children’s Hospital of Philadelphia
Section of Gastroenterology and Hepatology Department of Pediatrics, University of
Dartmouth-Hitchcock Medical Center Pennsylvania Perelman School of Medicine
Lebanon, NH, USA Philadelphia, PA, USA
xl Contributors

Giovanni Marchegiani, MD, PhD Bertrand Napoléon, MD

Department of Surgery Department of Gastroenterology
Pancreas Institute of the Verona University Hospital Ramsay Générale de Santé
Verona, Italy Private Hospital Jean Mermoz
Lyon, France
Julia Mayerle, MD
Department of Medicine II John P. Neoptolemos, MA, MB, BChir, MD, FRCS,
University Hospital FMedSci, MAE
Ludwig-Maximilians-Universität München Department of General, Visceral and
Munich, Germany Transplantation Surgery
University of Heidelberg
Antonio Mendoza-Ladd, MD, FACG, FASGE Heidelberg, Germany
Assistant Professor of Medicine
Texas Tech University El Paso Søren Schou Olesen, MD, PhD
Medical Director of Endoscopy Centre for Pancreatic Diseases and Mech-Sense
University Medical Center of El Paso Department of Gastroenterology and Hepatology,
El Paso, TX, USA Aalborg University Hospital
Department of Clinical Medicine, Aalborg University
Fabio F. di Mola, MD, PhD Aalborg, Denmark
Surgical Oncology Unit
Chee Y. Ooi, MBBS, Dip Paeds, FRACP, PhD
G. D’Annunzio University
Department of Gastroenterology, Sydney Children’s
Pierangeli Clinic
Hospital, Randwick
Pescara, Italy
Molecular and Integrative Cystic Fibrosis (miCF)
Research Centre, Randwick
Francesca Muffatti, MD
Discipline of Paediatrics, School of Women’s and
Pancreas Translational and Clinical Research
Children’s Health
Center
University of New South Wales
Pancreatic Surgery IRRCS San Raffaele Hospital
Sydney, NSW, Australia
Vita-Salute San Raffaele University
Milan, Italy
Kofi W. Oppong, BM, FRCP
Freeman Hospital
Rajarshi Mukherjee, MA (Cantab), MBBChir, FRCS
Institute of Cellular Medicine, Newcastle University
(Eng.), PhD, FAcadTM
Newcastle upon Tyne, UK
Liverpool Pancreatitis Research Group
Institute of Translational Medicine Laura Padula, MS, RDN, LDN
University of Liverpool Clinical Dietitian, Cystic Fibrosis Center
Liverpool, UK Department of Clinical Nutrition
Children’s Hospital of Philadelphia
Thiruvengadam Muniraj, MD, PhD Philadelphia, PA, USA
Section of Digestive Disease
Yale University School of Medicine Christopher Paiji, MD
New Haven, CT, USA Johns Hopkins University
Baltimore, MD, USA
Elena Muñoz-Forner, PhD
Liver, Biliary and Pancreatic Unit Paolo Panaccio, MD
Department of General Surgery Surgical Oncology Unit
Hospital Clínico, University of Valencia G. D’Annunzio University
Biomedical Research Institute INCLIVA Pierangeli Clinic
Valencia, Spain Pescara, Italy
 Contributors xli

Stephen J. Pandol, MD Angela Pham, MD

Professor of Medicine Assistant Professor of Medicine
Division of Gastroenterology, University of Division of Gastroenterology, Hepatology,
California at Los Angeles and Nutrition
Director, Center for Basic and Translational Pancreas University of Florida
Research Gainesville, FL, USA
Cedars Sinai Medical Center
Los Angeles, CA, USA Mary Phillips, BSc (Hons), RD DipADP
Advanced Specialist Dietitian (Hepato-pancreatico-
Georgios I. Papachristou, MD, PhD biliary Surgery)
Division of Gastroenterology, Hepatology, and Royal Surrey County Hospital NHS Foundation Trust
Nutrition Guildford, Surrey, UK
Department of Internal Medicine
Ohio State University Wexner Medical Center Romano C. Pirola, MD, FRACP
Columbus, OH, USA Pancreatic Research Group, South Western Sydney
Clinical School
Stefano Partelli, MD, PhD Faculty of Medicine, UNSW Sydney, Sydney;
Pancreas Translational and Clinical Research Ingham Institute for Applied Medical Research
Center Liverpool, New South Wales, Australia
Pancreatic Surgery IRRCS San Raffaele Hospital
Vita-Salute San Raffaele University Ignazio Piseddu
Milan, Italy Department of Medicine II
University Hospital
Mario Peláez-Luna, MD Ludwig-Maximilians-Universität München
Associate Professor of Medicine Munich, Germany
Research Division, School of Medicine
Universidad Nacional Autónoma de México; Jan-Werner Poley, MD, PhD
Pancreatic Unit, Department of Gastroenterology Department of Gastroenterology and Hepatology
Instituto Nacional de Ciencias Médicas y Nutrición Erasmus MC University Medical Center
Salvador Zubirán Rotterdam, the Netherlands
Mexico City, Mexico
Ignasi Poves, MD, PhD
Rossana Percario, MD Deceased September 2019
Surgical Oncology Unit Formerly Department of Surgery, Hospital del Mar
G. D’Annunzio University Universidad Autónoma de Barcelona
Pierangeli Clinic Barcelona, Spain
Pescara, Italy
Sarah Powell-Brett, MBChB, MRCS
Anna Pesci, MD Hepatobiliary and Pancreatic Surgeon
Pathology, IRCCS Sacro Cuore Don Calabria Queen Elizabeth Hospital
Hospital Birmingham, UK
Negrar, Italy
Nicolò de Pretis, MD, PhD
Raffaele Pezzilli, MD Department of Medicine
Department of Gastroenterology Pancreas Center
Sant Carlo Hospital University of Verona
Potenza, Italy Verona, Italy
xlii Contributors

Vinciane Rebours, MD, PhD Mercedes Rodríguez, MD

Pancreatology Department, Beaujon Hospital Medical Oncology Department
Assistance Publique – Hôpitaux de Paris Clichy Ramon y Cajal University Hospital
Paris Diderot University Madrid, Spain
Paris, France
Jonas Rosendahl, MD
D. Nageshwar Reddy, DM Department of Internal Medicine I
Chairman Martin Luther University
Asian Institute of Gastroenterology Hospitals Halle-Wittenberg, Germany
Hyderabad, India
Gemma Rossi, MD
Elizabeth Reid, MS, RDN, LDN Pancreas Translational and Clinical Research Center
Clinical Dietitian, Cystic Fibrosis Center Division of Pancreato-Biliary Endoscopy and
Department of Clinical Nutrition Endosonography
Children’s Hospital of Philadelphia San Raffaele Scientific Institute
Philadelphia, PA, USA Vita-Salute San Raffaele University
Milan, Italy
Bernhard W. Renz, MD
Department of General, Visceral, and Luis Sabater, MD, PhD
Transplantation Surgery Liver, Biliary and Pancreatic Unit
Ludwig Maximilian University Hospital Department of General Surgery
Munich, Germany Hospital Clínico, University of Valencia
Biomedical Research Institute INCLIVA
Carmen Mota Reyes, MD Valencia, Spain
Department of Surgery, Klinikum rechts der Isar
Technical University of Munich, School of Medicine Anand V. Sahai, MD, MSc (Epid.)
Munich, Germany Division of Gastroenterology
Center Hospitalier de l’Université de Montréal
Mihai Rimbaș, MD, PhD Montreal, Canada
Digestive Endoscopy Unit, Fondazione
Policlinico Universitario A. Gemelli IRCCS, Rome, Ashok K. Saluja, PhD
Italy Professor and Vice Chair
Gastroenterology and Internal Medicine Sylvester Comprehensive Cancer Center
Departments, Colentina Clinical Hospital, Carol DeWitt Daughtry Family Department of Surgery,
Davila University of Medicine, Bucharest, Romania University of Miami
Miami, FL, USA
Gianenrico Rizzatti, MD
Digestive Endoscopy Unit Patricia Sánchez-Velázquez, MD, PhD, FEBS
Fondazione Policlinico Universitario A. Gemelli Attending Surgeon
IRCCS Department of Surgery, Hospital del Mar
Rome, Italy Universidad Autónoma de Barcelona
Barcelona, Spain
Keith J. Roberts, PhD, FRCS
Consultant Liver Transplant, Hepatobiliary and Marta Sandini, MD
Pancreatic Surgeon Department of General, Visceral and
Queen Elizabeth Hospital Birmingham Transplantation Surgery
Honorary Reader, University of Birmingham University of Heidelberg
Birmingham, UK Heidelberg, Germany
 Contributors xliii

Hjalmar C. van Santvoort, MD, PhD Jordan K. Swensson, MD

Department of Surgery Indiana University School of Medicine
St. Antonius Hospital, Nieuwegein; Indianapolis, IN, USA
University Medical Center Utrecht
Utrecht, the Netherlands Peter Szatmary, PhD
Liverpool Pancreatitis Research Group
Juan José Serrano, MD Institute of Translational Medicine
Medical Oncology Department University of Liverpool
Ramon y Cajal University Hospital Liverpool, UK
Madrid, Spain
Rupjyoti Talukdar, MD
Ajaypal Singh, MD Asian Institute of Gastroenterology Hospitals
Digestive Diseases and Interventional Hyderabad, India
Gastroenterology
Rush University Medical Center – University
Gonzalo Tardáguila de la Fuente, MD
Gastroenterologists
Department of Radiology
Chicago, IL, USA
Hospital Povisa
Vigo, Spain
Vikesh K. Singh, MD, MSc
Division of Gastroenterology, and Pancreatitis Center
Johns Hopkins Medical Institutions Sabrina Gloria Giulia Testoni, MD
Baltimore, MD, USA Pancreas Translational and Clinical Research
Center
Andrea Soriano-Ríos, MD Division of Pancreato-Biliary Endoscopy and
Pancreatic Unit, Department of Gastroenterology Endosonography
Instituto Nacional de Ciencias Médicas y Nutrición San Raffaele Scientific Institute
Salvador Zubirán Vita-Salute San Raffaele University
Mexico City, Mexico Milan, Italy

Virginia A. Stallings, MD Hester C. Timmerhuis, MD

Professor of Pediatrics Dutch Pancreatitis Study Group
Division of Gastroenterology, Hepatology, and St. Antonius Ziekenhuis
Nutrition Nieuwegein, the Netherlands
Children’s Hospital of Philadelphia
Department of Pediatrics, University of Temel Tirkes, MD
Pennsylvania Perelman School of Medicine Indiana University School of Medicine
Phildalphia, PA, USA Indianapolis, IN, USA

Pauline M. C. Stassen, MD Luis Uscanga-Dominguez, MD

Department of Gastroenterology and Hepatology Pancreatic Unit, Department of Gastroenterology
Erasmus MC University Medical Center Instituto Nacional de Ciencias Médicas y Nutrición
Rotterdam, the Netherlands Salvador Zubirán
Mexico City, Mexico
Robert Sutton, BA (Hons), MB, BS, DPhil, FRCS
Liverpool Pancreatitis Research Group Giuseppe Vanella, MD
Institute of Translational Medicine Digestive Diseases Unit, Sant’Andrea Hospital
University of Liverpool Sapienza University of Rome
Liverpool, UK Rome, Italy
xliv Contributors

Jean-Luc Van Laethem, MD, PhD Frank Ulrich Weiss, PhD

Department of Gastroenterology, Hepatology and Department of Medicine A
Digestive Oncology University Medicine Greifswald
Erasme University Hospital Greifswald, Germany
Université Libre de Bruxelles
Bruxelles, Belgium Jens Werner, MD, MBA
Director and Chairman
Shyam Varadarajulu, MD Professor of Surgery
Center for Interventional Endoscopy Department of General, Visceral, and Transplant
AdventHealth Orlando Surgery
Orlando, FL, USA Ludwig Maximilian University Hospital
Munich, Germany
Santhi Swaroop Vege, MD, FACG
Mayo Clinic
Rochester, MN, USA David C. Whitcomb, MD, PhD
Professor of Medicine, Cell Biology and Molecular
Theodor Voiosu, MD, PhD Physiology, and Human Genetics
Gastroenterology Department, Colentina Clinical Division of Gastroenterology, Hepatology and
Hospital Nutrition
Internal Medicine Department, Carol Davila School University of Pittsburgh
of Medicine Pittsburgh, PA, USA
Bucharest, Romania
Jeremy S. Wilson, MD, FRCP, FRACP
Miroslav Vujasinovic, MD, PhD Pancreatic Research Group, South Western Sydney
Senior Consultant Clinical School
Department for Digestive Diseases Faculty of Medicine, UNSW Sydney, Sydney;
Karolinska University Hospital Ingham Institute for Applied Medical Research
Stockholm, Sweden Liverpool, New South Wales, Australia

Erik-Jan Wamsteker, MD
Associate Professor of Medicine
Department of Internal Medicine
Division of Gastroenterology and Hepatology
University of Michigan School of Medicine
Ann Arbor, MI, USA
Irving Waxman, MD
Sara and Harold Lincoln Thompson Professor of
Medicine and Surgery
Center for Endoscopic Research and Therapeutics
University of Chicago
Chicago, IL, USA
Christa J. Sperna Weiland, MD
Dutch Pancreatitis Study Group
St. Antonius Ziekenhuis
Nieuwegein, the Netherlands
John A. Windsor, BSc, MBChB, DipObst, MD(Thesis),
FRACS, FACS, FASA(Hons), FRSNZ
Professor of Surgery
Department of Surgery, University of Auckland
Department of Surgery, Auckland City Hospital
Auckland, New Zealand
Aimee Joy Wiseman, MBBS
Department of Gastroenterology
Sydney Children’s Hospital
Randwick, NSW, Australia
Jonathan M. Wyse, MD, MSc (Epid.)
Division of Gastroenterology
Jewish General Hospital
McGill University
Montreal, Canada
 Contributors xlv

Dhiraj Yadav, MD, MPH Felix Zubia-Olaskoaga, MD, PhD

Division of Gastroenterology and Hepatology
University of Pittsburgh Medical Center
Pittsburgh, PA, USA
Giuseppe Zamboni, MD
Department of Pathology, University of Verona
Pathology, IRCCS Sacro Cuore Don Calabria
Hospital
Negrar, Italy
Intensive Care Unit, Donostia University Hospital
BioDonostia, Group of Therapeutic Intervention in
Cardiovascular Diseases, Osakidetza Basque Health
Service
Department of Medicine, Euskal Herriko
Unibertsitatea–University of the Basque Country
Donostia/San Sebastian, Spain
xlvi
F
­ oreword
Pancreatic diseases represent an enigma to many physi-
cians, even gastroenterologists and surgeons. Nevertheless,
it encompasses a plethora of diseases that can severely
affect the well-being of any individual. Sound knowledge is
therefore pivotal to provide clinical care for these patients.
Pancreatologists have for long been pronounced an endan-
gered species [1], triggering special efforts in postgraduate
eductation [2].
It is the merit of the editor, J. Enrique Domínguez-
Muñoz, an esteemed and experienced gastroenterologist
and pancreatologist who has left his mark in the field, to
pull together an international group of highly recognized
colleagues who themselves have made landmark contribu-
tions enlightening all of gastroenterology, pancreatology,
and pancreatic surgery. One might ask whether in this day
and age a textbook is needed. This book, the second edition
of Clinical Pancreatology, proves that the answer to this
is yes! In one physical place, everything related to the
pancreas and its diseases, malfunction and affections, in
conjunction with other aspects relevant to clinical practice,
are covered. This book will provide reading for gastroenter-
ologists, surgeons as well as fellows in pancreatology and
anyone interested in pancreatic diseases. I trust that this
second edition will be as well received and cherished as the
first one.
J. -Matthias Löhr
Professor of Gastroenterology and Hepatology
Karolinska Institutet
Secretary, European Pancreas Club (EPC)
1 Schmid R. Pancreatologists: an endangered species?
Gastroenterology 2010;138:1236.
2 Gasslander T, Holmberg B, Permert J. Pancreas 2000: a new
concept for education and development in pancreatology.
Pancreatology 2005;5:545–546.
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at the Italian opera in Paris; but the only foundation for such a report
seems to be that it was not uncommon for violinist composers of that
period to enlist the aid of their friends in writing for the orchestra.
Viotti was a broadly educated musician, whose experience with
orchestras was wide.

Second in importance to the concertos are the duets for two violins
written during his stay in Hamburg. These are considered second in
musical charm only to Spohr’s pieces in the same manner. That
Viotti was somewhat low in spirit when he was at work on them,
exiled as he was from London and Paris, is shown by the few words
prefixed to one of the sets, ‘This work is fruit of the leisure which
misfortune has brought me. Some pieces came to me in grief, others
in hope.’

Viotti had a brilliant and unrestricted technique. He was among the

greatest of virtuosi. But little of this appears in his music. That is
distinguished by a dignity and a relative simplicity, well in keeping
with the noble traditions inherited from a country great in more ways
than one in the musical history of the eighteenth century. But as far
as form and style go he is modern. He undoubtedly owes something
to Haydn. Moreover, Wasielewski makes the point that there is no
trace in his music of the somewhat churchly dignity one feels in the
sonatas of Corelli and Tartini. Viotti’s is a thoroughly worldly style, in
melody and in the fiery but always musical passage work. He is at
once the last of the classic Italians and the first of the moderns,
standing between Corelli and Tartini on the one hand and Spohr,
David, and Vieuxtemps on the other.

The list of the men who came to him for instruction while he was in
Paris contains names that even today have an imposing ring. Most
prominent among them are Rode, Cartier, and Durand. And among
those who were not actually his pupils but who accepted him as their
ideal and modelled themselves after him were Rodolphe Kreutzer
and Pierre Baillot. These men are the very fountain head of most
violin music and playing of the nineteenth century. They set the
standard of excellence in style and technique by which Spohr and
later Vieuxtemps ruled themselves.

IV
Before considering their work, the development of violin music in
Germany during the eighteenth century must be noticed. The
influence of the Italians was not less strong here than in France.
Both Biber and Strungk had come under it in the late seventeenth
century, Strungk being, as we know, personally acquainted with
Corelli and at one time associating closely with him in Rome. The
German violinists of the eighteenth century either went to Italy to
study, or came under the influence of various Italians who passed
through the chief German cities on concert tours.

The most conspicuous of them are associated with courts or cities

here and there. For instance, early in the century there is Telemann
in Hamburg; a little later Pisendel in Dresden; J. G. Graun in Berlin;
Leopold Mozart in Salzburg; the gifted Stamitz and his associates
Richter, Cannabich and Fränzl in Mannheim; and the most amiable if
not the most gifted of all, Franz Benda, here and there in Bohemia,
Austria and Saxony. Though these and many more were widely
famous in their day as players, and Mozart was influential as a
teacher, little of their music has survived the centuries that have
passed since they wrote it. The eighteenth century was in violin
music and likewise in opera, the era of Italian supremacy; and in
violin music we meet with little except copies outside of Italy.

Georg Philipp Telemann, it is true, wrote that he followed the French

model in his music; but as Wasielewski says, this applies evidently
only to his vocal works and overtures, for his violin compositions are
very clearly imitations of Corelli’s. All his music, and he wrote
enormous quantities in various branches, is essentially
commonplace. Between 1708 and 1721 Telemann occupied a
position at the court of Eisenach. It was chiefly during these years
that he gave himself to the violin and violin music. Afterwards he
went to Hamburg and there worked until his death in 1767.

Johann Georg Pisendel is a far more distinguished figure. He was

born on the twenty-sixth of December, 1687, at Carlsburg in
Franconia, and died in Dresden, after many years’ service there, in
November, 1755. While still a boy the Marquis of Anspach attached
him to his chapel, on account of his beautiful voice. In the service of
the same prince at that time was Torelli, the great Italian composer
for the violin; and Pisendel was his pupil for a considerable period.
Later in life he was able to journey in Italy and France, and was
apparently at one time a pupil of Vivaldi’s in Venice. From 1728 to
the time of his death he was first violin in the royal opera house at
Dresden. His playing was distinguished by care in shading, and in
his conducting he was said to have laid great importance upon ‘loud
and soft.’ As a composer he is without significance, though some of
his works—concertos and sonatas—have been preserved. But his
influence served to educate violinists in that part of Germany, so that
little by little Germans came to supplant the Italians in that branch of
music, and to find occupation in connection with the opera house
orchestra, which had been up to that time almost entirely made up of
Italians.

Most conspicuous among those who were actually his pupils was
Johann Gottlieb Graun, brother of the still familiar Carl Heinrich. But
Graun was not content with instruction in Germany alone, and
betook himself to Tartini in Padua. After his return to his native land,
he eventually found his place at the court of Frederick the Great,
who was still crown prince. With him at this time were Quantz, the
flute player, and Franz Benda. After the accession of Frederick to the
throne of Prussia, Graun was made first violin and concert master in
the royal orchestra; and he held this place until his death in 1771.
His compositions, like all others for the violin at this period, are
hardly more than imitations of the Italian masterpieces. And like
Pisendel, his importance is in the improvement of the state of
instrumental music in Germany, and especially of the orchestra at
Berlin.
His successor in this royal orchestra was Franz Benda, who, not only
by reason of the romantic wanderings of his life, is one of the most
interesting figures in the history of music in Germany during the
eighteenth century. His father, Hans Georg, had been a sort of
wandering player, as well as a weaver; and his brothers, Johann,
Georg, and Joseph, were all musicians who won a high place in their
day. Georg was perhaps the most distinguished of the family, but in
the history of violin-music Franz occupies a more important place.

The Bendas were Bohemians, but most of them settled in Germany

and accepted German ideals and training. Franz Benda, after a
changing career as a boy singer in various places, finally came
under the influence of Graun and Quantz in the crown prince’s
orchestra, at Rheinsberg. The principal instruction he received upon
the violin came from Graun, who was himself a pupil of Tartini’s; so,
although Benda shows the marks of an independent and self-
sufficient development, not a little of Italian influence came close to
him. He remained in the service of the Prussian court from 1733,
when Quantz befriended him, until his death as an old man in 1786.

His playing was admired for its warm, singing quality, which showed
to such advantages in all slow movements that musicians would
come long distances to hear him play an adagio. Burney heard him
in 1772 and was impressed by the true feeling in his playing. Burney,
too, mentioned that in all Benda’s compositions for the violin there
were no passages which should not be played in a singing and
expressive manner. He went on to say that Benda’s playing was
distinguished in this quality from that of Tartini, Somis, and Veracini,
and that it was something all his own which he had acquired in his
early association with singers.

He had indeed been a great singer, and he gave up public singing

only because after singing he was subject to violent headache. He
trained his two daughters to be distinguished singers of the next
generation.

His works for the violin are numerous, but only a small part of them
was published, and this posthumously. In spite of the often lovely
melodies in the slow movements they have not been able to outlive
their own day. Wasielewski calls attention to the general use of
conventional arpeggio figures in the long movements, which,
characteristic of a great deal of contemporary music for the violin,
may have been written with the idea of offering good technical
exercise in the art of bowing.

Among Benda’s many pupils the two most significant are his own
son, Carl, and Friedrich Wilhelm Rust. The former seems to have
inherited a great part of his father’s skill and style. The sonatas of the
latter are among the best compositions written in Germany for the
violin in the second half of the eighteenth century. Rust died in
February, 1798. His name is remembered as much for his sonatas
for pianoforte as for his violin compositions. Another pupil, Carl
Haack, lived until September, 1819, and thus was able to carry the
Benda tradition over into the nineteenth century. On the whole Franz
Benda may be said to have founded a school of violin playing in
Berlin which has influenced the growth of music for that instrument in
Germany. Its chief characteristic was the care given to simplicity and
straightforwardness, especially in the playing of slow movements
and melodies, which stands out quite distinctly against the current of
more or less specious virtuosity running across the century.

Johann Peter Salomon (1745-1815) has been associated with the

Berlin group, though his youth was spent in and about Bonn, and his
greatest activity was displayed as an orchestral conductor in London.
It was he who engaged Haydn to come to London and to compose
symphonies specially for a London audience; and he occupies an
important place in the history of music in England as one of the
founders (1813) of the Philharmonic Society. He published but little
music, and that is without significance.

One of the outstanding figures in the history of violin music in

Germany is Leopold Mozart, the father of Wolfgang. He is hardly
important as a composer, though many of his works were fairly well
known in and about Salzburg where the greatest part of his life was
spent; but his instruction book on playing the violin marks the
beginning of a new epoch in his own country. This was first
published in Augsburg in 1756, was reprinted again in 1770, 1785,
and in Vienna in 1791 and 1804. It was for many years the only book
on the subject in Germany.

Much of it is now old-fashioned, but it still makes interesting reading,

partly because he was far-seeing enough to seize upon fundamental
principles that have remained unchanged in playing any instrument,
partly because the style is concise and the method clear, partly
because of the numerous examples it contains of both good and bad
music. Evidently his standard of excellence is Tartini, so that we still
find violin music in Germany strongly under the influence of the
Italians. But the great emphasis he lays upon simplicity and
expressiveness recalls Benda and his ideals, so that it would appear
that some wise men in Germany were at least shrewd enough to
choose only what was best in the Italian art. Among the many
interesting points he makes is that it takes a better-trained and a
more skillful violinist to play in an orchestra than to make a success
as a soloist. Evidently many of the German musicians distrusted the
virtuoso. Emanuel Bach, it will be remembered, cared nothing for
show music on the keyboard. C. F. D. Schubart, author of the words
of Schubert’s Die Forelle, said that an orchestra made up of virtuosi
was like a world of queens without a ruler. He had the orchestra at
Stuttgart in mind.

V
Meanwhile about the orchestra at Mannheim there was a band of
gifted young men whose importance in the development of the
symphony and other allied forms has been but recently recognized,
and now, it seems, can hardly be overestimated. The most
remarkable of these was J. C. Stamitz, a Bohemian born in 1719,
who died when less than forty years old. His great accomplishments
in the domains of orchestral music have been explained elsewhere
in this series. In the matter of violin music he can hardly be said to
show any unusual independence of the Italians, but in the meagre
accounts of his life there is enough to show that he was a great
violinist. He was the teacher of his two sons, Carl (1746-1801) and
Anton (b. 1753), the latter of whom apparently grew up in Paris,
where the father, by the way, had been well known at the house of
La Pouplinière. Anton, as we shall see, was the teacher of Rodolphe
Kreutzer, already mentioned as one of the great teachers at the
Paris Conservatory in the first of the nineteenth century.

Christian Cannabich, a disciple if not a pupil of Stamitz, was likewise

a famous violinist, but again like his master, was more influential in
what he accomplished with the famous orchestra at Mannheim than
in his playing or composing for the violin. He seems to have spent
some years in Naples to study with Jomelli, and the Italian influence
is evident in all he wrote for the violin. Wilhelm Cramer, the father of
the now more famous J. B. Cramer, was another violinist associated
with the Mannheim school, until in 1773 he went to London on the
advice of Christian Bach. Here he lost one place after another as
conductor, owing now to the arrival of Salomon, now to that of Viotti.
He died in 1799 in great poverty.

Others connected with the orchestra at Mannheim are Ignaz Fränzl,

whose pupil, F. W. Pixis, became the teacher of Kalliwoda and Laub,
and whose son Ferdinand (1770-1833) was a distinguished violinist
in the next century; and Johann Friedrich Eck (b. 1766) and his
brother Franz. Their father was, like Stamitz, a Bohemian. Indeed
Stamitz seems to have induced Eck the elder to leave Bohemia and
come to Mannheim. Franz Eck is most famous today as one of the
teachers of Ludwig Spohr.

In Vienna the Italian influence was supreme down to nearly the end
of the century. The first of the Viennese violinists to win an
international and a lasting renown was Karl Ditters von Dittersdorf (b.
1739), the friend of Haydn and Gluck. Though two of his teachers,
König and Ziegler, were Austrians, a third, who perfected him, was
an Italian, Trani. Through Trani Dittersdorf became familiar with the
works of Corelli, Tartini, and Ferrari, after which he formed his own
style. Practically the first German to draw a circle of pupils about him
was Anton Wranitzky (b. 1761). Among his pupils the most
distinguished was Ignaz Schuppanzigh, who, as the leader of the
Schuppanzigh quartet, won for himself an immortal fame, and really
set the model for most quartet playing throughout the nineteenth
century. He was the son of a professor at the Realschule in Vienna.
From boyhood he showed a zeal for music, at first making himself a
master of the viola. At the time Beethoven was studying counterpoint
with Albrechtsberger he was taking lessons on the viola with
Schuppanzigh. Later, however, Schuppanzigh gave up the viola for
the violin. His most distinguished work was as a quartet leader, but
he won fame as a solo player as well; and when the palace of Prince
Rasoumowsky was burned in 1815, he went off on a concert tour
through Germany, Poland and Russia which lasted many years. He
was a friend not only of Beethoven, but of Haydn, Mozart, and of
Schubert as well; and was the principal means of bringing the
quartet music of these masters to the knowledge of the Viennese
public. He died of paralysis, March 2, 1830. Among his pupils the
most famous was Mayseder, at one time a member of the quartet.

What is noteworthy about the German violinist-composers of the

eighteenth century is not so much the commonness with which they
submitted to the influence of the Italians, but the direction their art as
players took as soon as they began to show signs of a national
independence. Few were the match of the Italians or even the
French players in solo work. None was a phenomenal virtuoso. The
greatest were most successful as orchestral or quartet players; and
their most influential work was that done in connection with some
orchestra. This is most evident in the case of the Mannheim
composers. Both Stamitz and Cannabich were primarily conductors,
who had a special gift in organizing and developing the orchestra.
Their most significant compositions were their symphonies, in the
new style, in which they not only gave a strong impetus to the
development of symphonic forms, but brought about new effects in
the combination of wood-wind and brass instruments with the
strings. Leopold Mozart’s opinion that a man who could play well in
an orchestra was a better player and a better musician than he who
could make a success playing solos, is indicative of the purely
German idea of violin music during the century. And it cannot be
denied that great as Franz Benda and Johann Graun may have been
as players, they contributed little of lasting worth to the literature of
the violin, and made practically no advance in the art of playing it.
But both were great organizers and concert masters, and as such
left an indelible impression on the development of music, especially
orchestral music, in Germany.

VI
Before concluding this chapter and passing on to a discussion of the
development of violin music in the nineteenth century a few words
must be said of the compositions for the violin by those great
masters who were not first and foremost violinists. Among these,
four may claim our attention: Handel, Bach, Haydn, and Mozart.

Handel is not known to have given much time to the violin, but it is
said that when he chose to play on it, his tone was both strong and
beautiful. He wrote relatively little music for it. Twelve so-called solo
sonatas with figured bass (harpsichord or viol) were published in
1732 as opus 1. Of these only three are for the violin: the third, tenth,
and twelfth. The others are for flute. Apart from a few characteristic
violin figures, chiefly of the rocking variety, these solo sonatas might
very well do for clavier with equal effect. There is the sane, broad
mood in them all which one associates with Handel. In the edition of
Handel’s works by the German Handel Society, there are three
additional sonatas for violin—in D major, A major, and E major.
These seem to be of somewhat later origin than the others, but they
are in the same form, beginning with a slow movement, followed by
allegro, largo, and final allegro, as in most of the cyclical
compositions of that time. One cannot deny to these sonatas a
manly dignity and charm. They are in every way plausible as only
Handel knows how to be; yet they have neither the grace of Corelli,
nor the deep feeling of Bach. One may suspect them of being, like
the pieces for clavier, tossed off easily from his pen to make a little
money. What is remarkable is that sure as one might be of this, one
would yet pay to hear them.

There are besides these solo sonatas for violin or flute and figured
bass, nine sonatas for two violins, or violin and flute with figured
bass, and seven sonatas, opus 5, for two instruments, probably
intended for two violins.

Among the most remarkable of J. S. Bach’s compositions are the six

sonatas for violin without any accompaniment, written in Cöthen,
about 1720. These works remain, and probably always will remain,
unique in musical literature, not only because of their form, but
because of the profound beauty of the music in them. Just how much
of a violinist Bach himself was, no one knows. He was fond of
playing the viola in the court band at Cöthen. It can hardly be
pretended that these sonatas for violin alone are perfectly adapted to
the violin. They resemble in style the organ music which was truly
the whole foundation of Bach’s technique. In that same organ style,
he wrote for groups of instruments, for groups of voices, for clavier
and for all other combinations.

On the other hand no activity of Bach’s is more interesting, and

perhaps none is more significant, than his assiduous copying and
transcribing again and again of the violin works of Vivaldi, Torelli, and
Albinoni. Especially his study of Vivaldi is striking. He used themes
of the Italian violinists as themes for organ fugues; he transcribed the
concertos of Vivaldi into concertos for one, two, three, or four
harpsichords. And not only that, practically all his concertos for a
solo clavier are transcriptions of his own concertos for violin.

But the polyphonic style of the sonatas for violin alone is peculiarly a
German inheritance. Walter and Biber were conspicuous for the use
of double stops and an approach to polyphonic style. Most
remarkable of all was a pupil of the old Danish organist, Buxtehude,
Nikolaus Bruhns (1665-1697), who was able to play two parts on his
violin and at the same time add one or two more with his feet on the
organ pedals. Though Corelli touched gently upon the polyphonic
style in the movements of the first six of his solo sonatas, the
polyphonic style was maintained mostly by the Germans. As Bach
would write chorus, fugue, or concerto in this style, so did he write
for the violin alone.

Of the six works the first three are sonatas, in the sense of the
sonate da chiesa of Corelli, serious and not conspicuously
rhythmical. The last three are properly suites, for they consist of
dance movements. The most astonishing of all the pieces is the
Chaconne, at the end of the second suite. Here Bach has woven a
series of variations over a simple, yet beautiful, ground, which finds
an equal only in the great Passacaglia for the organ.

The three sonatas of this set can be found transcribed, at least in

part, by Bach into various other forms. The fugue from the first, in G
minor, was transposed into D minor and arranged for the organ. The
whole of the second sonata, in A minor, was rearranged for the
harpsichord. The fugue in the third sonata for violin alone exists also
as a fugue for the organ.

There are besides these sonatas for violin alone, six sonatas for
harpsichord and violin, which are among the most beautiful of his
compositions; and a sonata in E minor and a fugue in G minor for
violin with figured bass. It is interesting to note that the six sonatas
for harpsichord and violin differ from similar works by Corelli and by
Handel. Here there is no affair with the figured bass; but the part for
the harpsichord is elaborately constructed, and truly, from the point
of view of texture, more important than that for the violin.

Bach wrote at least five concertos for one or two violins during his
stay at Cöthen. One of these is included among the six concertos
dedicated to the Margrave of Brandenburg. All of these have been
rearranged for harpsichord, and apparently among the harpsichord
concertos there are three which were originally for violin but have not
survived in that shape. The concertos, even more than the sonatas,
are not essentially violin music, but are really organ music. The style
is constantly polyphonic and the violin solos hardly stand out
sufficiently to add a contrasting spot of color to the whole. Bach’s
great work for the violin was the set of six solo sonatas. These must
indeed be reckoned, wholly apart from the instrument, as among the
great masterpieces in the musical literature of the world.

Haydn’s compositions for violin, including concertos and sonatas,

are hardly of considerable importance. His associations with
violinists in the band at Esterhazy, and later in Vienna with amateurs
such as Tost and professionals like Schuppanzigh, gave him a
complete idea of the nature and the possibilities of the instrument.
But the knowledge so acquired shows to best advantage in his
treatment of the first and second violin parts in his string quartets, in
many of which the first violin is given almost the importance of a solo
instrument. Eight sonatas for harpsichord and violin have been
published, but of these only four were originally conceived in the
form.

The young Mozart was hardly less proficient on the violin than he
was on the harpsichord, a fact not surprising in view of his father’s
recognized skill as a teacher in this special branch of music. But he
seems to have treated his violin with indifference and after his
departure from Salzburg for Paris to have quite neglected his
practice, much to his father’s concern. The most important of his
compositions for the violin are the five concertos written in Salzburg
in 1775. They were probably written for his own use, but just how
closely in conjunction with the visit of the Archduke Maximilian to
Salzburg in April of that year cannot be stated positively. Several
serenades and the little opera, Il re pastore, were written for the fêtes
given in honor of the same young prince. The concertos belong to
the same period. In Köchel’s Index they are numbers 207, 211, 216,
218, and 219. A sixth, belonging to a somewhat later date, bears the
number 268. Of these the first in B-flat was completed on April 14,
1775, the second, in D, June 14, the third, in G, September 12, the
fourth, in D, in October, and the fifth, in A, quite at the end of the
year.

The sixth concerto, in E-flat, is considered both by Jahn and Köchel

to belong to the Salzburg period. It was not published, however, until
long after Mozart’s death; and recently the scholarly writers, Messrs.
de Wyzewa and de St. Foix, have thrown considerable doubt upon
the authenticity of large parts of it. According to their theory[50] the
opening tutti and the orchestral portion at the beginning of the
development section are undoubtedly the work of Mozart, but of the
mature Mozart of 1783 and 1784. Likewise the solo passages in all
the movements seem to bear the stamp of his genius. But apart from
these measures, the development of the solo ideas and the
orchestral accompaniment were completed either by André, who
published the work, or by Süssmayer, who was also said by Mozart’s
widow to be the composer of a mass in B-flat, published by C. F.
Peters as a composition of Mozart’s.

In addition mention should be made of the concertos introduced

between the first and second movements of various serenades,
according to the custom of the day. Most of these are of small
proportions; but one, in G major (K. 250), written in Salzburg some
time in July, 1776, has the plan of an independent composition.

It was the custom for a master like Schobert in Paris, or Mozart in

Vienna, to ‘accompany’ the young ladies who played pianoforte or
harpsichord sonatas of his composition and under his instruction with
music on the violin. There are many sonatas for harpsichord
published by Schobert, with a violin part ad libitum. This in the main
but reinforces the chief melodic lines of the part for harpsichord or
pianoforte; and works with such a violin part, ad libitum, are not at all
violin sonatas in the sense of the term accepted today, i.e., sonatas
in which violin and piano are woven inextricably together. They are
frankly pianoforte or harpsichord sonatas with the ‘accompaniment’
of a violin.

On the other hand, we have found the violin masters like Corelli and
Tartini writing sonatas for violin, with figured bass for harpsichord,
lute, or even viol. Such sonatas were often called solo sonatas, as in
the case of those of Handel, recently mentioned. The accompanying
instrument had no function but to add harmonies, and a touch of
imitation in the written bass part, here and there.
Between these two extremes lies the sonata with harpsichord
obbligato, that is to say, with a harpsichord part which was not an
accompaniment but an essential part of the whole. In these cases
the music was generally polyphonic in character. The violin might
carry one or two parts of the music, the harpsichord two or three.
Very frequently, if the instruments played together no more than
three parts, the composition was called a Trio. The sonatas by J. S.
Bach for harpsichord and violin are of this character. Though the
harpsichord carries on more of the music than the violin, both
instruments are necessary to the complete rendering of the music.

Mozart must have frequently added improvised parts for the violin to
many of his sonatas written expressly for the keyboard instrument.
Among his earliest works one finds sonatas for clavecin with a free
part for violin, for violin or flute, for violin or flute and 'cello. Oftenest
the added part does little more than duplicate the melody of the part
for clavecin, with here and there an imitation or a progression of
thirds or sixths. But among his later works are sonatas for pianoforte
with added accompaniment for violin in which the two instruments
contribute something like an equal share to the music, which are the
ancestors of the sonatas for violin and piano by Beethoven, Brahms,
and César Franck. Among the most important of these are six
published in November, 1781, as opus 2. In Köchel’s Index they bear
the numbers 376, 296, 377, 378, 379, and 380. The greatest of them
is that in C major, K. 296, with its serious and rich opening adagio, its
first allegro in Mozart’s favorite G minor, and the beautiful variations
forming the last movement. Four more sonatas, of equal musical
value, were published respectively in 1784, 1785, 1787, and 1788.

VII
Looking back over the eighteenth century one cannot but be
impressed by the independent growth of violin music. The Italians
contributed far more than all the other nationalities to this steady
growth, partly because of their native love for melody and for sheer,
simple beauty of sound. The intellectual broadening of forms, the
intensifying of emotional expressiveness by means of rich and
poignant harmonies, concerned them far less than the perfecting of a
suave and wholly beautiful style which might give to the most singing
of all instruments a chance to reveal its precious and almost unique
qualities. This accounts for the calm, classic beauty of their music,
which especially in the case of Corelli and Tartini does not suffer by
changes that have since come in style and the technique of
structure.

The success of the Italian violinists in every court of Europe, both as

performers and as composers, was second only to the success of
the great singers and the popular opera composers of the day. Their
progress in their art was so steadfast and secure that other nations
could hardly do more than follow their example. Hence in France and
Germany one finds with few exceptions an imitation of Italian styles
and forms, with a slight admixture of national characteristics, as in
the piquancy of Cartier’s, the warm sentiment of Benda’s music.
What one might call the pure art of violin playing and violin music,
abstract in a large measure from all other branches of music, was
developed to perfection by the Italian violinist-composers of the
eighteenth century. Its noble traditions were brought over into more
modern forms by Viotti, henceforth to blend and undergo change in a
more general course of development.

Perhaps only in the case of Chopin can one point to such a pure and
in a sense isolated ideal in the development of music for a single
instrument, unless the organ works of Bach offer another exception.
And already in the course of the eighteenth century one finds here
and there violin music that has more than a special significance. The
sonatas for unaccompanied violin by Bach must be regarded first as
music, then as music for the violin. The style in which they were
written is not a style which has grown out of the nature of the
instrument. They have not served and perhaps cannot serve as a
model for perfect adaptation of means to an end. Bach himself was
willing to regard the ideas in them as fit for expression through other
instruments. But the works of Corelli, Tartini, Nardini and Viotti are
works which no other instrument than that for which they were
written may pretend to present. And so beautiful is the line of melody
in them, so warm the tones which they call upon, that there is
scarcely need of even the harmonies of the figured bass to make
them complete.

In turning to the nineteenth century we shall find little or no more of

this sort of pure music. Apart from a few brilliant concert or salon
pieces which have little beyond brilliance or charm to recommend
them, the considerable literature for the violin consists of sonatas
and concertos in which the accompaniment is like the traditional half,
almost greater than the whole. In other words we have no longer to
do with music for which the violin is the supreme justification, but
with music which represents a combination of the violin with other
instruments. Glorious and unmatched as is its contribution in this
combination, it remains incomplete of itself.
 FOOTNOTES:
[48] See A. Schering: Geschichte des Instrumentalkonzerts.

[49] Die Violine und ihre Meister.

[50] See ‘W. A. Mozart,’ by T. de Wyzewa and G. de St. Foix, Paris, 1912.
Appendix II, Vol. II, p. 428.
 CHAPTER XIII
VIOLIN MUSIC IN THE NINETEENTH
CENTURY
The perfection of the bow and of the classical technique—The
French school: Kreutzer, Rode, and Baillot—Paganini: his
predecessors, his life and fame, his playing, and his compositions
—Ludwig Spohr: his style and his compositions; his pupils—
Viennese violinists: Franz Clement, Mayseder, Boehm, Ernst and
others—The Belgian school: De Bériot and Vieuxtemps—Other
violinist composers: Wieniawski, Molique, Joachim, Sarasate, Ole
Bull; music of the violinist-composers in general—Violin music of
the great masters.

The art of violin music in the nineteenth century had its head in
Paris. Few violinists with the exception of Paganini developed their
powers without the model set them by the great French violinists at
the beginning of the century. Most of them owed more than can be
determined to the influence of Viotti. Even Spohr, who with more or
less controversial spirit, wrote of the French violinists as old-
fashioned, modelled himself pretty closely upon Rode; and therefore
even Spohr is but a descendant of the old classical Italian school.

The technique of playing the violin was thoroughly understood by the

end of the eighteenth century. Viotti himself was a brilliant virtuoso;
but, trained in the classic style, he laid less emphasis upon external
brilliance than upon expressiveness. The matters of double stops,
trills, runs, skips and other such effects of dexterity were largely
dependent upon the fingers of the left hand; and this part of
technique, though somewhat hampered by holding the violin with the
chin upon the right side of the tailpiece, was clearly mastered within
reasonable limits by the violinists of the middle of the century, Tartini,
Veracini, Nardini, Geminiani, and others. Indeed Geminiani in his
instruction book recommended that the violin be held on the left side;
and in range of fingering gave directions for playing as high as in the
seventh position. Leopold Mozart, however, naturally conservative,
held to the old-fashioned holding of the instrument.

The technique of bowing, upon which depends the art of expression

in violin playing, awaited the perfection of a satisfactory bow. Tartini’s
playing, it will be remembered, was especially admired for its
expressiveness; and this, together with certain of his remarks on
bowing which have been preserved in letters, leads one to think that
he may have had a bow far better than those in the hands of most of
his contemporaries. Whether or not he made it himself, and indeed
just what it may have been, are not known. Certainly it must have
been better than the bows with which Leopold Mozart was familiar.
The clumsy nature of these may be judged by the illustrations in his
instruction book.

The final perfection of the bow awaited the skill of a Frenchman,

François Tourte (1747-1835), who has properly been called the
Stradivari of the bow. It was wholly owing to his improvements that
many modern effects in staccato, as well as in fine shading,
particularly in the upper notes, became possible. He is supposed not
to have hit upon these epoch-making innovations until after 1775;
and there is much likelihood that he was stimulated by the presence
of Viotti in Paris after 1782. No better testimony to the service he
rendered to the art of violin playing can be found than the new
broadening of violin technique and style accomplished by men like
Viotti, Kreutzer, Baillot, Rode, and Lafont, who availed themselves
immediately of the results of his skill.

I
Something may now be said of these men, whose activities have
without exception the glaring background of the horrors of the
French Revolution. Though Kreutzer was of German descent, he
was born in Versailles (1766) and spent the greater part of his life in
and about Paris, intimately associated with French styles and
institutions. Apart from early lessons received from his father, he
seems to have been for a time under the care of Anton Stamitz, son
of Johann Stamitz. At the Chapelle du Roi, to which organization he
obtained admittance through the influence of Marie Antoinette, he
had the occasion of hearing Viotti. The great Italian influenced him
no less than he influenced his young contemporaries in Paris.
Concerning his activities as a composer of operas little need be said,
though one or two of his ballets, especially Paul et Virginie and Le
Carnaval de Venise, held the stage for some years. As a player he
ranks among the most famous of the era. His duets with Rode
roused the public to great enthusiasm. In 1798 he was in Vienna in
the suite of General Bernadotte, and here made the acquaintance of
Beethoven. Subsequently Beethoven dedicated the sonata for violin
and piano (opus 47) to Kreutzer.

By reason of this and his book of forty Études ou caprices pour le

violon, he is now chiefly remembered. His other compositions for the
violin, including nineteen concertos and several airs and variations,
have now been allowed to sink into oblivion. To say that the
concertos are ‘more brilliant than Rode’s, less modern than Baillot’s’
distinguishes them as much as they may be distinguished from the
compositions of his contemporaries. They are dry music, good as
practice pieces for the student, but without musical life. But Kreutzer
was a great teacher. He was one of the original professors of the
violin at the Conservatoire, and with Baillot and Rode prepared the
still famous Méthode which, carrying the authority of that sterling
institution, has remained, almost to the present day, the standard
book of instruction for the young violinist. His own collection of forty
studies likewise holds still a place high among those ‘steps to
Parnassus’ by which the student may climb to the company of
finished artists.