Title Details

The Editors
HANS G. BEGER, MD, FACS(Hon), JSS(Hon), CSS(Hon), Founding Editor, Professor Emeritus of Surgery, c/o University of Ulm, Ulm, Germany

ANDREW L. WARSHAW, MD, FACS, FRCSEd(Hon), W. Gerald Austen Distinguished Professor of Surgery, Harvard Medical School, Surgeon-in-Chief Emeritus, Massachusetts General Hospital, Boston, MA, USA

RALPH H. HRUBAN, MD, Baxley Professor and Director, The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

MARKUS W. BÜCHLER, MD, Professor of Surgery and Chair, Department of Surgery, University of Heidelberg, Heidelberg, Germany

MARKUS M. LERCH, MD, FRCP, Professor and Chair, Department of Medicine A, University Medicine Greifswald, Greifswald, Germany

JOHN P. NEOPTOLEMOS, MA, MB, BCHIR, MD, FRCS, FMEDSCI, Professor of Surgery, Department of Surgery, University of Heidelberg, Heidelberg, Germany

TOORU SHIMOSEGAWA, MD, PhD, Professor, Department of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

DAVID C. WHITCOMB, MD, PhD, Professor of Medicine, Cell Biology & Physiology, and Human Genetics, Director, UPMC Precision Medicine Service, University of Pittsburgh and UPMC, Pittsburgh, PA, USA

Contributors xiii

Preface xxix

Abbreviations xxx

About the Companion Website xlii

Section 1 Anatomy of the Pancreas 1

1 Development of the Pancreas and Related Structures 3
Brian Lewis and Junhao Mao

2 Anatomy, Histology, and Fine Structure of the Pancreas 10
Daniel S. Longnecker, Fred Gorelick, and Elizabeth D. Thompson

3 Congenital and Inherited Anomalies of the Pancreas 24
Martin Zenker and Markus M. Lerch

Section 2 Physiology and Pathophysiology of Pancreatic Functions 41

4 Physiology of Acinar Cell Secretion 43
Ole H. Petersen

5 Physiology of Duct Cell Secretion 56
Mei Zeng, Laura Vachel, and Shmuel Muallem

6 Pathophysiology of Experimental Pancreatitis 63
Vikas Dudeja, Rajinder Dawra, and Ashok K. Saluja

7 Physiology and Pathophysiology of Function of Sphincter of Oddi 75
Savio George Barreto and James Toouli

8 Neurohormonal and Hormonal Control of Pancreatic Secretion 84
Chung Owyang

9 Regulation of Pancreatic Protein Synthesis and Growth 95
Maria Dolors Sans and John A. Williams

10 Fibrogenesis in the Pancreas: The Role of Stellate Cells 106
Minoti V. Apte, Romano C. Pirola, and Jeremy S. Wilson

11 Fibrogenesis of the Pancreas: The Role of Macrophages 117
Aida Habtezion

12 Insulo–Acinar Relationship 123
Keiko Shiratori and Kyoko Shimizu

Section 3 Acute Pancreatitis 133

13 Epidemiology and Etiology of Alcohol‐Induced Pancreatitis 135
Jeremy S. Wilson, Romano C. Pirola, and Minoti V. Apte

14 Epidemiology and Etiology of Acute Biliary Pancreatitis 146
Michael G.T. Raraty, Andrea Sheel, and John P. Neoptolemos

15 Genetic Factors in Acute Pancreatitis 158
Zachary Zator and Georgios I. Papachristou

16 The Role of the Intestine and Mesenteric Lymph in the Development of Systemic Inflammation and MODS in Severe Acute Pancreatitis 166
Alistair B.J. Escott, Anthony R.J. Phillips, and John A. Windsor

17 The Role of Neurogenic Inflammation in Pancreatitis 173
Jami L. Saloman, Kathryn M. Albers, and Brian M. Davis

18 Molecular, Biochemical, and Metabolic Abnormalities in Acute Pancreatitis 178
Julia Mayerle, Frank Ulrich Weiss, Walter Halangk, and Markus M. Lerch

19 Histopathology of Acute Pancreatitis 193
Günter Klöppel

20 Clinical Classification Systems of Acute Pancreatitis 199
John A. Windsor and Max S. Petrov

21 Clinical Assessment and Biochemical Markers to Objectify Severity and Prognosis 204
Bettina M. Rau and Guido Alsfasser

22 Acute Pancreatitis Associated With Congenital Anomalies 213
Christopher R. Schlieve, Andrew L. Warshaw, and Tracy C. Grikscheit

23 Acute Pancreatitis in Children 219
Mark E. Lowe and Véronique D. Morinville

24 Acute Pancreatitis Associated With Metabolic Disorders, Infectious Diseases, or Drugs 230
Ali A. Aghdassi and Markus M. Lerch

25 Radiologic Diagnosis and Staging of Severe Acute Pancreatitis 238
Yoshihisa Tsuji

Clinical Course and Medical Treatment of Acute Pancreatitis 251

26 Conservative Therapy of Acute Pancreatitis: Volume Substitution and Enteral and Parenteral Nutrition 251
Timothy B. Gardner

27 ICU Treatment of Severe Acute Pancreatitis 258
Scott R. Gunn and David C. Whitcomb

28 Use of Antibiotics in Severe Acute Pancreatitis: Indications and Limitations 265
Rainer Isenmann and Mathias Wittau

Interventional and Surgical Management of Acute Pancreatitis 271

29 Indications for Interventional and Surgical Treatment of Necrotizing Pancreatitis 271
Thomas E. Clancy

30 Management of Infected Pancreatic Necroses: An Endoscopic Approach 277
Eduardo Rodrigues‐Pinto and Todd H. Baron

31 Minimally Invasive Debridement and Lavage of Necrotizing Pancreatitis 283
Rebecca Saunders, Michael G.T. Raraty, Chris Halloran, and John P. Neoptolemos

32 Open Surgical Debridement in Necrotizing Pancreatitis 289
Lutz Schneider and Markus W. Büchler

33 Endoscopic Treatment of Biliary Acute Pancreatitis 296
Ichiro Yasuda, Shinpei Doi, and Masatoshi Mabuchi

34 Strategies for the Treatment of Pancreatic Pseudocysts and Walled‐Off Necrosis After Acute Pancreatitis: Interventional Endoscopic Approaches 301
Georg Beyer, Julia Mayerle, and Markus M. Lerch

35 Strategies for the Treatment of Pancreatic Pseudocysts and Walled‐Off Necrosis After Acute Pancreatitis: Surgical Treatment 305
Naohiro Sata, Masaru Koizumi, and Alan K. Lefor

36 Management of Fluid Collection in Acute Pancreatitis 311
Felix Lämmerhirt, Frank Ulrich Weiss, and Markus M. Lerch

37 Management of Pancreatic Fistula in Acute Pancreatitis 316
Jörg Kaiser, Thilo Hackert, and Markus W. Büchler

Long-Term Outcome After Treatment of Acute Pancreatitis 323

38 Long‐Term Outcome After Acute Pancreatitis 323
Christin Tjaden and Thilo Hackert

Section 4 Chronic Pancreatitis 331

39 Molecular Understanding of Chronic Pancreatitis 333
John F. Eisses and Sohail Z. Husain

40 Epidemiology and Pathophysiology of Alcoholic Chronic Pancreatitis 342
Atsushi Masamune and Tooru Shimosegawa

41 Pain Mechanisms in Chronic Pancreatitis 349
Pierluigi di Sebastiano, Tommaso Grottola, and Francesco F. di Mola

42 Natural History of Recurrent Acute and Chronic Pancreatitis 355
Rohit Das and Dhiraj Yadav

43 Chronic Pancreatitis with Inflammatory Mass of the Pancreatic Head 365
Ulrich F. Wellner and Tobias Keck

44 Early Chronic Pancreatitis 371
Tetsuhide Ito, Masayuki Hijioka, and Tooru Shimosegawa

45 Hereditary Chronic Pancreatitis: Molecular Pattern, Clinical Consequences, and Management Principles 374
Celeste Shelton and David C. Whitcomb

46 Epidemiology and Pathophysiology of Tropical Chronic Pancreatitis 384
Shailesh V. Shrikhande and Savio George Barreto

47 Cystic Fibrosis (CFTR)‐Associated Pancreatic Disease 391
Chee Y. Ooi and Aliye Uc

48 Clinical and Laboratory Diagnosis of Chronic Pancreatitis 397
Julia Mayerle, Peter Simon, and Markus M. Lerch

49 Evidence of Contrast‐Enhanced CT and MRI/MRCP 406
J. Enrique Domínguez‐Muñoz, Roberto García‐Figueiras, and Julio Iglesias‐García

50 Chronic Pancreatitis: Risk Factors in Cancer 417
Albert B. Lowenfels and Patrick Maisonneuve

Conservative Treatment of Chronic Pancreatitis 421

51 Pain Management in Chronic Pancreatitis 421
Kai Bachmann, Stephanie Plagemann, Yogesh Kumar Vashist, and Jakob R. Izbicki

52 Medical Treatment of Chronic Pancreatitis: Pancreatic Digestive Enzymes: Lipases, Proteases 426
Mark E. Lowe

53 Nutritional Support of Chronic Pancreatitis 429
Sinead N. Duggan and Stephen J. O’Keefe

54 Medical Therapy for Chronic Pancreatitis: Antioxidants 435
Chris E. Forsmark

Strategies for Endoscopic and Surgical Treatment of Chronic Pancreatitis 439

55 Evidence of Endoscopic and Interventional Treatment of Chronic Pancreatitis and Pseudocysts 439
Jörg Schirra, Markus M. Lerch, and Julia Mayerle

56 Indications and Goals of Surgical Treatment 449
Ryan T. Groeschl and Michael B. Farnell

57 Pancreatic Duct Drainage Procedure 453
Dirk Bausch and Tobias Keck

58 Duodenum‐Preserving Pancreatic Head Resection 458
Hans G. Beger, Bertram Poch, Yang Yinmo, and Waldemar UhlContents vii

59 Major Pancreatic Resection 467
May C. Tee and Michael B. Farnell

60 Laparoscopic Surgery 479
Vernissia Tam, Melissa E. Hogg, and Amer Zureikat

Management of Diabetes and Long-Term Outcome of Chronic Pancreatitis 488

61 Chronic Pancreatitis: Long‐Term Outcome After Medical and Surgical Treatment 488
Volker Aßfalg, Norbert Hüser, and Helmut Friess

62 Management of Pancreatic Diabetes Secondary to Chronic Pancreatitis 495
Keiko Shiratori

Section 5 Autoimmune Pancreatitis 503

63 Epidemiology of Autoimmune Pancreatitis 505
Terumi Kamisawa and Tooru Shimosegawa

64 Pathogenesis of Autoimmune Pancreatitis 510
Yoh Zen

65 Histology of Autoimmune Pancreatitis 516
Rajib Gupta and Vikram Deshpande

66 Clinical Manifestation of Type 1 Autoimmune Pancreatitis 520
Tooru Shimosegawa, Morihisa Hirota, and Atsushi Kanno

67 Clinical Manifestations of Type 2 Autoimmune Pancreatitis 534
Emma L. Culver and George Webster

68 Laboratory Diagnosis of Autoimmune Pancreatitis 539
J.‐Matthias Löhr, Pia Maier, and Stephan L. Haas

69 What is the Evidence Measuring Immune Markers 544
Shigeyuki Kawa

70 Imaging Diagnosis of Autoimmune Pancreatitis 550
Kazuichi Okazaki, Tsukasa Ikeura, Kazushige Uchida, and Makoto Takaoka

71 Medical Management of Autoimmune Pancreatitis 555
Shounak Majumder and Suresh T. Chari

Long-Term Outcome of Management of Autoimmune Pancreatitis 560

72 Long‐Term Outcome After Treatment of Autoimmune Pancreatitis 560
Luca Frulloni and Nicolò de Pretis

Section 6 Neoplastic Tumors of the Exocrine Tissue: Benign Cystic Neoplasms of the Pancreas 565

73 Epidemiology of Cystic Neoplasms of the Pancreas 567
Saurabh Mukewar and Suresh T. Chari

74 Histologic Classification and Staging of Cystic Neoplasms 573
Noriyoshi Fukushima and Giuseppe Zamboni

75 Molecular Mechanisms of Cystic Neoplasia 580
Nickolas Papadopoulos and Ralph H. Hruban

76 Clinical Presentation of Cystic Neoplasms 589
Susumu Hijioka, Kazuo Hara, Nobumasa Mizuno, Nozomi Okuno, and Kenji Yamao

77 Evaluation of Cystic Lesions Using EUS, MRI, and CT 593
Anne Marie Lennon and Hiroyuki Maguchi

78 Cytologic Evaluation of Cystic Neoplasms 603
Martha Bishop Pitman

79 Natural History of Cystic Neoplasms: IPMN, MCN, SCN, and SPN 611
Anna‐Katharina Stadler, Thilo Hackert, Stefan Fritz, and Markus W. Büchler

80 Surveillance or Surgical Treatment in Asymptomatic Cystic Neoplasms 618
Klaus Sahora and Carlos Fernández‐ del Castillo

Local and Standard Surgical Treatment of Cystic Neoplasms 622

81 Duodenum‐Preserving Partial or Total Pancreatic Head Resection 622
Hans G. Beger and Bertram Poch

82 Pancreatic Middle Segment Resection 627
Calogero Iacono

83 The Indications For and Limitations of Tumor Enucleation 632
Rosalie A. Carr, C. Max Schmidt, and Henry A. Pitt

84 Standard Surgical Management of IPMN, MCN, SPN, and SCN Lesions: Open Approach 641
Miral Sadaria Grandhi, Barish H. Edil, and Richard D. Schulick

85 Surgical Treatment of Cystic Neoplasms: Laparoscopic Approach 649
Richard A. Burkhart, Christopher L. Wolfgang, Markus W. Büchler, and Thilo Hackert

86 Management of Recurrence of Cystic Neoplasms 655
Zhi Ven Fong, Christopher L. Wolfgang, and Keith D. Lillemoe

Long-Term Outcome of Management of Cystic Neoplasms 660

87 Long‐Term Outcome After Observation and Surgical Treatment: What is the Evidence? 660
Giovanni Marchegiani, Giuseppe Malleo, and Claudio Bassi

Section 7 Neoplastic Tumors of Exocrine Tissue: Pancreatic Cancer 665

88 Epidemiology of Pancreatic Cancer 667
Evelina Mocci and Alison P. Klein

89 Smoking, a Risk for Pancreatic Cancer: Experimental and Clinical Data 673
Uwe A. Wittel, Bradley R. Hall, and Surinder K. Batra

90 Molecular Understanding of Development of Ductal Pancreatic Cancer 679
Laura D. Wood and Ralph H. Hruban

91 Familial Pancreatic Cancer 688
Alison P. Klein

92 Pathology of Exocrine Pancreatic Tumors 693
Meredith E. Pittman and Ralph H. Hruban

93 Pancreatic Cancer: Precancerous Lesions 705
Michaël Noë, Lodewijk A.A. Brosens, and Johan Offerhaus

94 Clinical History and Risk Factors of Pancreatic Cancer 717
Norbert Hüser, Volker Aßfalg, and Helmut Friess

95 Pancreatic Cancer Within the Uncinate Process: Radiologic and Clinical Characteristics 724
Sebastian Holländer and Dieter Birk

96 The Role of EUS in the Diagnosis and Differential Diagnosis of Neoplastic Lesions 728
Susumu Hijioka, Kazuo Hara, Nobumasa Mizuno, Nozomi Okuno, and Kenji Yamao

97 Radiologic Diagnosis of Pancreatic Cancer: CT, MRI 733
Siva P. Raman and Elliot K. Fishman

98 Screening of Patients with Hereditary Pancreatic Cancer 745
Michael Goggins

99 The Role of PET in Diagnosis of Pancreatic Cancer and Cancer Recurrence 755
Norbert Hüser, Volker Aßfalg, Isabel Rauscher, and Helmut Friess

100 Tumor Markers in Pancreatic Malignancies 762
Shin Hamada, Atsushi Masamune, and Tooru Shimosegawa

101 The Role of Laparoscopy and Peritoneal Cytology in the Management of Pancreatic Cancer 766
Kyoichi Takaori and Shinji Uemoto

102 Clinical Assessment and Staging of Advanced Pancreatic Cancer 770
Jennifer LaFemina, Ann K. Friedrich, and Giles F. Whalen

Surgical Treatment of Pancreatic Cancer 776

103 Pancreatic Cancer: Indications for Resection 776
Akimasa Nakao

104 Pancreaticoduodenectomy for Pancreatic Cancer, Short‐ and Long‐Term Outcomes After Kausch–Whipple and Pylorus‐Preserving Resection 783
Jin He and John L. Cameron

105 Left Pancreatectomy for Body and Tail Cancer 790
Georgios Gemenetzis and Christopher L. Wolfgang

106 Total Pancreatectomy: Indications and Limitations 797
Seiko Hirono and Hiroki Yamaue

107 Laparoscopic and Robotic Resection for Pancreatic Cancer 804
Deepa Magge, Herbert J. Zeh, and Melissa E. Hogg

108 Extended Radical Surgery for Pancreatic Cancer 814
Thilo Hackert, Alexis Ulrich, and Markus W. Büchler

109 Palliative Pancreatoduodenectomy: Benefits and Limitations 823
Christoph W. Michalski, Max Heckler, Mert Erkan, and Markus W. Büchler

110 Bypass Surgery for Advanced Pancreatic Cancer 828
Jürgen Weitz, Thomas Pausch, Christoph W. Michalski, and Thilo Hackert

Nonsurgical Palliation of Pancreatic Cancer 835

111 Endoscopic and Interventional Palliation of Pancreatic Cancer 835
Takao Itoi

Medical Treatment of Pancreatic Cancer 842

112 Neoadjuvant Treatment of Pancreatic Cancer: Downstaging Results 842
Robert A. Wolff and Gauri Varadhachary

113 Adjuvant Chemotherapy in Pancreatic Cancer 847
Robert P. Jones, Paula Ghaneh, and John P. Neoptolemos

114 Immunotherapy for Pancreatic Cancer 856
Adrian G. Murphy, Elizabeth M. Jaffee, and Lei Zheng

115 Targeted Therapies for Pancreatic Cancer 865
Vincent Bernard and Anirban Maitra

116 Palliative Chemotherapy for Advanced Pancreatic Cancer: Survival Benefit and Side Effects of Treatment 872
Olusola O. Faluyi, Madhuchanda Chatterjee, and Daniel H. Palmer

117 Management of Pain in Pancreatic Cancer 879
Michael Erdek, Indy Wilkinson, and Zackary E. Boomsaad

118 Role of Radio and Proton Beam Therapy for Pancreatic Cancer 886
Amol K. Narang, Lauren M. Rosati, Michael D. Chuong, and Joseph M. Herman

119 Management of Cancer Recurrence 895
Oliver Strobel and Markus W. Büchler

Long-Term Outcome After Treatment of Pancreatic Cancer 906

120 Survival and Late Morbidity After Resection of Pancreatic Cancer 906
Avinoam Nevler, Charles J. Yeo, and Jordan M. Winter

Section 8 Neoplastic Tumors of the Endocrine Pancreas: Neuroendocrine Tumors of the Pancreas 919

121 Epidemiology and Classification of Neuroendocrine Tumors of the Pancreas 921
J.J. Mukherjee, Kok‐Onn Lee, and Gregory Kaltsas

122 Pathology of Neuroendocrine Neoplasms 930
Atsuko Kasajima and Hironobu Sasano

123 Molecular Genetics of Neuroendocrine Tumors 937
Nickolas Papadopoulos and Ralph H. Hruban

124 Clinical Manifestation of Endocrine Tumors of the Pancreas 947
Ken Kawabe and Tetsuhide Ito

125 Evidence of Hormonal, Laboratory, Biochemical, and Instrumental Diagnostics of Neuroendocrine Tumors of the Pancreas 953
Kok‐Onn Lee, Gregory Kaltsas, and J.J. Mukherjee

126 Pancreatic Neuroendocrine Tumors in Multiple Neoplasia Syndromes 961
Anja Rinke and Thomas Matthias Gress

127 Nonfunctioning Pancreatic Neuroendocrine Tumors: Diagnosis and Management Principles 967
Takao Ohtsuka, Hideyo Kimura, and Masafumi Nakamura

128 Medical and Nucleotide Treatment of Neuroendocrine Tumors of the Pancreas 972
Gregory Kaltsas, J.J. Mukherjee, and Kok‐Onn Lee

129 Interventional Radiology in the Treatment of Pancreatic Neuroendocrine Tumors 979
Takao Ohtsuka, Hideyo Kimura, and Masafumi Nakamura

Surgical Management of Endocrine Tumors of the Pancreas 982

130 Surgical Treatment of Endocrine Tumors: Enucleation 982
Henning Dralle, Phuong Nguyen Thanh, and Andreas Machens

131 Local Treatment of Endocrine Tumors: Duodenum‐Preserving Partial or Total Pancreatic Head Resection and Pancreatic Middle‐Segment Resection 989
Hans G. Beger and Wataru Kimura

132 Surgical Treatment of Endocrine Tumors: Major Oncologic Resection 994
Henning Dralle, Phuong Nguyen Thanh, and Andreas Machens

133 Management of Insulinoma 1002
Keijiro Ueda, Linkaku Lee, and Tetsuhide Ito

134 Evidence of Medical and Surgical Treatment of Gastrinoma 1009
Ryuichiro Doi

135 Rare Neuroendocrine Tumors of the Pancreas: Management and Evidence of Surgical Treatment 1013
Ryuichiro Doi

136 Treatment of Neuroendocrine Tumors of the Pancreas and Biliary Tract 1019
Andrea Frilling, Ashley K. Clift, and Vito Cincinnati

Long-Term Outcome After Treatment of Neuroendocrine Tumors of the Pancreas 1029

137 Long‐Term Outcome After Treatment of Endocrine Tumors 1029
Andreas Machens and Henning Dralle

Section 9 Periampullary Cancers and Tumors Other Than Pancreatic Cancer 1035

138 Periampullary Cancer: Clinical Presentation and Diagnostic Strategies 1037
Amanda B. Cooper and Keith D. Lillemoe

139 Histology and Genetics of Cancer of the Papilla, Distal Common Bile Duct, and Duodenum 1047
Yue Xue, Michelle D. Reid, and N. Volkan Adsay

140 Adenoma and Adenocarcinoma of the Ampulla of Vater: Diagnosis and Management 1058
Omer Basar and William R. Brugge

141 Endoscopic Treatment of Adenomas of the Ampulla of Vater: Techniques, Results, Benefits, and Limitations 1068
Natsuyo Yamamoto, Hiroyuki Isayama, and Kazuhiko Koike

142 Surgical Treatment of Adenoma and Cancer of Papilla of Vater 1074
Hans G. Beger, Bertram Poch, and Bettina M. Rau

143 Surgical Treatment of Duodenal Cancer 1081
Fuyuhiko Motoi and Michiaki Unno

144 Surgical Treatment of Distal Cholangiocarcinoma 1083
Yukihiro Yokoyama, Tomoki Ebata, and Masato Nagino

145 Adjuvant and Palliative Chemotherapy of Periampullary Cancers 1089
Eyas Mohamed, Paula Ghaneh, and John P. Neoptolemos

Long-Term Survival After Tumor Resection 1097

146 Long‐Term Survival After Resection of Periampullary Cancer 1097
Masayuki Ohtsuka and Masaru Miyazaki

Section 10 Transplantation of the Pancreas 1107

147 Transplantation of Pancreatic Islets 1109
Bernhard J. Hering and Melena D. Bellin

148 Transplantation of the Pancreas 1121
Hans W. Sollinger and Dixon B. Kaufman

Index 1129