Yamada's Textbook of Gastroenterology (eBook)
John Wiley & Sons (Verlag)
9781118512159 (ISBN)
Yamada's Textbook of Gastroenterology has for 20 years been the most comprehensive gastroenterology reference book, combining an encyclopaedic basic science approach to GI and liver disease with the latest clinical thinking, especially in diagnostic and therapeutic developments. It is universally respected across the globe.
The original outstanding editorial team was led by Tadataka Yamada, MD, one of the world's leading figures in GI research. As in previous editions, the new textbook reflects the collective efforts of the editors and a hugely impressive team of contributors, who are each experts in their specific areas.
Now with another world leader in gastroenterology as Editor-in-Chief, Daniel K. Podolsky MD, President and Professor of Internal Medicine at the University of Texas Southwestern Medical Center, together with a stellar group of associate editors, the 6th edition of this iconic textbook has been expanded and enhanced in many ways with new content and technology.
Editor-in-Chief:
Daniel K. Podolsky, M.D. President, Professor of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Associate Editors:
Michael Camilleri, M.D, Professor of Medicine and Physiology, College of Medicine, Mayo Clinic; Consultant in Gastroenterology, Mayo Clinic, Rochester.
J. Gregory Fitz, M.D, Dean, Southwestern Medical School, Distinguished Chair in Medical Science, UT Southwestern Medical Center, Dallas, TX, USA.
Anthony N. Kalloo, M.D, Professor of Gastroenterology and Director, Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, MD USA.
Fergus Shanahan, M.D, Professor and Chair, Department of Medicine and Director, Alimentary Pharmabiotic Centre, University College Cork, Cork University Hospital, Ireland.
Timothy C. Wang, M.D, Chief, Division of Digestive and Liver Diseases, Silberberg Professor Medicine, Department of Medicine and Irving Cancer Research Center, Columbia University Medical Center, New York, NY USA.
Yamada s Textbook of Gastroenterology has for 20 years been the most comprehensive gastroenterology reference book, combining an encyclopaedic basic science approach to GI and liver disease with the latest clinical thinking, especially in diagnostic and therapeutic developments. It is universally respected across the globe.The original outstanding editorial team was led by Tadataka Yamada, MD, one of the world's leading figures in GI research. As in previous editions, the new textbook reflects the collective efforts of the editors and a hugely impressive team of contributors, who are each experts in their specific areas. Now with another world leader in gastroenterology as Editor-in-Chief, Daniel K. Podolsky MD, President and Professor of Internal Medicine at the University of Texas Southwestern Medical Center, together with a stellar group of associate editors, the 6th edition of this iconic textbook has been expanded and enhanced in many ways with new content and technology.
Editor-in-Chief: Daniel K. Podolsky, M.D. President, Professor of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. Associate Editors: Michael Camilleri, M.D, Professor of Medicine and Physiology, College of Medicine, Mayo Clinic; Consultant in Gastroenterology, Mayo Clinic, Rochester. J. Gregory Fitz, M.D, Dean, Southwestern Medical School, Distinguished Chair in Medical Science, UT Southwestern Medical Center, Dallas, TX, USA. Anthony N. Kalloo, M.D, Professor of Gastroenterology and Director, Division of Gastroenterology and Hepatology, The Johns Hopkins Hospital, Baltimore, MD USA. Fergus Shanahan, M.D, Professor and Chair, Department of Medicine and Director, Alimentary Pharmabiotic Centre, University College Cork, Cork University Hospital, Ireland. Timothy C. Wang, M.D, Chief, Division of Digestive and Liver Diseases, Silberberg Professor Medicine, Department of Medicine and Irving Cancer Research Center, Columbia University Medical Center, New York, NY USA.
Cover 1
Title page 5
Copyright page 6
Contents 7
Contributors 13
Preface 29
Foreword by Tadataka Yamada 31
About the companion website and companion digital edition 33
PART 1: Anatomy and development 35
CHAPTER 1: Development and differentiation of the gastrointestinal system 37
Early development 37
Gastrulation and tube formation 38
Pattern formation 41
Fate and potential 41
Signaling in development 42
Transdifferentiation and dedifferentiation 45
Conclusions 45
Organogenesis 46
Liver 47
Pancreas 49
Gastrointestinal tract 52
Conclusions 54
Developmental physiology 55
Maturation of the gastrointestinal tract 55
Dietary control of gastrointestinal development 56
Hormonal control of gastrointestinal development 56
Development of the enteric nervous system 57
Mucosal immune system 58
Conclusions 58
Disorders of development 58
Disorders of specification and formation 58
Disorders of differentiation and patterning 60
Disorders of remodeling 61
Disorders of growth control 63
Conclusions 63
Further reading 64
CHAPTER 2: Stem cells and tissue renewal 65
Architecture and function of the gastrointestinal tract 65
Role of the Wnt signaling pathway in the intestine 66
Role of the Notch signaling pathway in the intestine 68
Intestinal stem cells 69
Acknowledgments 75
Further reading 75
CHAPTER 3: Esophagus: anatomy and structural anomalies 76
Embryology (see Chapter 1) 76
Adult anatomy 76
Gross anatomy 76
Blood supply (see Chapter 11) 78
Innervation (see Chapter 15) 80
Lymphatics 80
Histology 81
Light microscopy (see Chapter 155) 81
Developmental anomalies 82
Congenital tracheoesophageal fistula and esophageal atresia 82
Congenital esophageal stenosis 83
Congenital esophageal duplication 84
Bronchopulmonary foregut malformation 84
Aortic arch vessel abnormalities producing extrinsic compression of the esophagus (dysphagia lusoria) 84
Heterotopic gastric mucosa (inlet patch) 85
Structural anomalies 86
Esophageal rings and webs 86
Cervical and midesophageal webs 88
Cricopharyngeal bar 88
Pharyngoesophageal and esophageal diverticula 89
Further reading 93
CHAPTER 4: Stomach and duodenum: anatomy and structural anomalies 94
Embryology of the stomach and duodenum 94
Gross anatomy of the stomach and duodenum 94
Anatomical relationships and divisions 94
Circulation 95
Lymphatics 97
Innervation 98
Microscopic anatomy 98
Congenital abnormalities of the stomach 102
Atresia 102
Mucosal membranes 102
Gastric duplication 102
Microgastria 102
Gastric teratoma 102
Gastric diverticula 103
Ectopic gastric mucosa 103
Hypertrophic pyloric stenosis 103
Congenital abnormalities of the duodenum 104
Atresias, stenosis, and membranes 104
Annular pancreas 104
Duplication 105
Malrotation 105
Superior mesenteric artery syndrome 105
Preduodenal portal vein 106
Duodenal diverticula 106
Further reading 106
CHAPTER 5: Small intestine: anatomy and structural anomalies 107
Embryology and development 107
Gross anatomy 107
Extrinsic arterial, venous, and lymphatic supply 108
Neural supply 109
Maximization of small intestinal surface area: gross and microscopic features 109
Microscopic anatomy 109
Serosa and muscularis propria 109
Submucosa 110
Mucosa 111
Congenital anomalies 116
Meckel diverticulum 116
Duplications 118
Intestinal atresia and stenosis 119
Malrotation 121
Gastroschisis and omphalocele 122
Structural anomalies 123
Volvulus 123
Intussusception 123
Lymphangiectasia 125
Celiac artery compression 126
Further reading 126
CHAPTER 6: Colon: anatomy and structural anomalies 127
Introduction 127
Gross anatomical considerations 127
Histology of the colon 131
Embryology 135
Colorectal malformations 135
Anorectal malformations 136
Blood supply and lymphatic drainage 137
Colonic volvulus 139
Further reading 141
CHAPTER 7: Pancreas: anatomy and structural anomalies 142
Embryological development 142
Gross anatomy 143
Surgical exposure 145
Arterial blood supply 146
Venous drainage 147
Lymphatic drainage 148
Nerve supply 148
Ductal system 150
Ultrastructure 151
Congenital anomalies 152
Agenesis or hypoplasia of the pancreas 152
Annular pancreas 152
Heterotopic pancreas 153
Pancreas divisum 153
Cystic lesions of the pancreas 154
Multiple cysts 155
Further reading 155
CHAPTER 8: Abdominal cavity: anatomy, structural anomalies, and hernias 156
Introduction 156
Abdominal cavity development and anatomy 156
Peritoneal embryology 156
Peritoneal reflections 157
Boundaries of the abdominal cavity 158
Developmental and childhood structural anomalies of the abdominal cavity 159
Disorders of bowel rotation 159
Congenital intraabdominal cystic lesions 160
Pediatric anterior abdominal wall hernias 160
Pediatric groin hernias 160
Pediatric diaphragmatic hernias 160
Adult abdominal hernias 161
Epidemiology 161
Pathogenesis 162
Clinical findings 162
Adult groin hernia 162
Adult nongroin abdominal wall hernias 163
Adult internal, pelvic, and diaphragmatic hernias 164
Conclusion 165
Further reading 165
CHAPTER 9: Gallbladder and biliary tract: anatomy and structural anomalies 167
Embryological development 167
Anatomy of the gallbladder 167
Gross anatomy 167
Arterial blood supply 168
Venous and lymphatic drainage 169
Nerve supply 169
Histology and ultrastructure 170
Anatomy of the extrahepatic biliary ducts 171
Hepatic ducts 171
Cystic duct 172
Common bile duct 173
Ampulla of Vater 173
Sphincter of Oddi 174
Arterial blood supply 175
Venous and lymphatic drainage 175
Histology and ultrastructure 175
Congenital variations and malformations 175
Gallbladder and cystic duct 175
Hepatic ducts and common bile duct 176
Biliary atresia 176
Choledochal cyst 178
Further reading 178
CHAPTER 10: Liver: anatomy, microscopic structure, and cell types 179
Embryology 179
Gross anatomy 181
Microanatomy 183
Normal histology 183
Parenchymal cellular components 184
Stroma (extracellular matrix) 190
Biliary network 190
Vascular and lymphatic network 190
Neural network 192
Functional components 192
Progenitor and stem cells (see Chapter 2) 193
Further reading 194
CHAPTER 11: Gastrointestinal blood flow 195
Anatomy of the gastrointestinal circulation 195
Extramural vessels 195
Intramural vessels and microcirculation 195
Mechanisms of blood flow regulation 196
Intrinsic systems 196
Extrinsic systems 199
Postprandial hyperemia 203
Constituents of chyme responsible for postprandial hyperemia 203
Mechanisms 204
Interactions between gastrointestinal and liver circulations 205
Portal venous hypertension 206
Pathophysiology of ischemia 207
Alterations of intestinal morphology with ischemia 207
Changes in vascular and mucosal permeability with ischemia 207
Blood flow, oxygenation, and ischemic injury 208
Possible mechanisms of injury or villous necrosis 209
Ischemic preconditioning 212
Gastrointestinal blood flow and physical exercise 213
Vascular responses to chronic inflammation 213
Angiogenesis 215
Further reading 216
PART 2: Mechanisms of normal and abnormal gastrointestinal function 217
A Components 219
CHAPTER 12: Integrative responses of the gastrointestinal tract, pancreas, and liver to a meal 219
Control systems 220
Endocrine regulation 220
Paracrine regulation 221
Neural regulation (see Chapters 14 and 15) 221
Enteric nervous system 221
Regulation of food intake by the gastrointestinal tract 221
Role of water 223
Cephalic and oral phases of a meal 223
Gastric phase of a meal 224
Duodenal signals regulating gastric, pancreatic, and hepatic functions 225
Nutrient digestion and absorption systems in the small intestine 228
Colonic phase of a meal 228
Regulation of nutrient storage and release: roles of the endocrine pancreas and liver 229
Fed state 229
Fasted state 230
Regulation of the metabolic state 231
Further reading 231
CHAPTER 13: Gastrointestinal hormones and receptors 232
Organization of the gut endocrine system 233
History of gastrointestinal endocrinology 235
Hormone secretory cells 236
Endocrine cell localization and characterization 236
Biosynthesis and processing of gastrointestinal hormones 237
Hormone and transmitter molecules 239
Measurement of hormones 240
Receptors 241
Receptor characterization and quantification 245
Hormone-specific insights 245
Gastrin–cholecystokinin family 245
Pancreatic polypeptide family 249
Tachykinin family 250
Somatostatin family 251
Motilin family 252
Protease-activated receptor family 252
Chemokine family 253
Secretin family 253
Tyrosine kinase receptor family 257
Toll-like receptor family 258
Hormones in gastrointestinal disease 258
Acknowledgments 259
Further reading 259
CHAPTER 14: The brain–gut axis 261
Introduction 261
Gut to brain communication 262
Intrinsic innervation – the enteric nervous system 262
Exstrinsic innervation – vagal and spinal pathways 262
Vagal afferents 262
Pelvic afferents 262
Spinal afferents 262
Central processing 264
Brain to gut communication 265
Emotional motor system 265
Corticotrophin-releasing hormone 265
Autonomic nervous system and cholingeric antiinflammatory pathway 266
Brain hypothalamic–pituitary–adrenal gut axis 267
Brain–gut microbiota axis 268
Brain–gut axis in the regulation of appetite and satiety (see Chapter 28) 268
Brain–gut axis dysfunction 270
Acute disturbances in brain–gut axis function 270
Chronic disturbances in brain–gut axis function 270
Functional gastrointestinal disorders 270
Conclusion 271
Further reading 271
CHAPTER 15: The innervation of the gastrointestinal tract 273
Overview 273
Structural organization of the enteric nervous system 275
Locations of the enteric ganglia 276
Nonganglionated plexuses innervating target tissues 276
Myenteric plexus 277
Submucosal plexus 277
Ganglia of the gallbladder, biliary ducts, and pancreas 277
Shapes of neurons 277
Histochemical profiles and transmitter multiplicity of enteric neurons 278
Physiological characteristics of enteric neurons 278
Electrophysiological properties of enteric neurons 278
Synaptic transmission in the enteric nervous system 278
Functionally defined enteric neurons 280
Motor neurons 280
Enteric interneurons 282
Intrinsic primary afferent neurons 283
Vagal innervation of the gastrointestinal tract 285
Motor (efferent) pathways 285
Sensory pathways 285
Pelvic nerves 286
Neural control of gastrointestinal movements 286
Overview 286
Esophagus 286
Stomach 287
Small intestine and colon 287
Neural control of secretion and mucosal blood flow 289
Overview 289
Enteric secretomotor and vasomotor reflexes 289
Responses to noxious stimuli 290
Sympathetic innervation 290
Sympathetic effects on secretion 290
Sympathetic effects on the gastrointestinal blood supply 291
Sympathetic effects on motility 291
Summary 291
Further reading 292
CHAPTER 16: Smooth muscle of the gut 293
Structure of smooth muscle 293
Muscle layers 293
Muscle cells: membranes and organelles 293
Contractile apparatus: thin and thick filaments 295
Interaction of contractile proteins 296
Phosphorylation of myosin light chain 296
Signal transduction in visceral smooth muscle 297
Source of activator calcium 297
Components of the transduction pathway 297
Effector enzymes and second messengers 298
IP3-dependent calcium mobilization in cells of the circular muscle layer 299
IP3-independent calcium mobilization in cells of the longitudinal muscle layer 300
Regulation of cytosolic calcium at rest and during contraction 300
Calcium-independent sustained contraction 301
Regional differences in smooth muscle signaling 301
Mechanisms of relaxation by protein kinase A and G 301
Desensitization of receptor function 303
Electrical properties of smooth muscle 303
Resting membrane potential 303
Gated ion-selective channels 303
Rhythmic electrical activity of smooth muscle 304
Control of rhythmic electrical activity by Ca2+ and K+ ion channels 304
Fast action potentials 304
Interstitial cells of Cajal: electrical pacemakers and mediators of enteric neurotransmission 304
Slow waves 305
Regional patterns of contractile activity 306
Stimulus–contraction coupling in syncytia: tonic and phasic contraction 309
Neural regulation of smooth muscle by the myenteric plexus 309
Neuronal topography 310
Peptide and other neurotransmitters 310
Peristaltic reflex 313
Hormonal regulation of smooth muscle function 314
Humoral regulation of smooth muscle function 315
Inflammation and smooth muscle 315
Smooth muscle cells: targets and source of inflammatory mediators 315
Role of nuclear factor-kappa B in inhibition of circular smooth muscle contractility 315
Effect of cytokines on targets in the signaling cascade mediating circular muscle contraction 316
Effect of cytokines on targets in the signaling cascade mediating longitudinal muscle contraction 316
Summary 316
Further reading 317
CHAPTER 17: The mucosal immune system and gastrointestinal inflammation 318
The mucosal immune system 318
General concepts of immunology 319
Cellular components of the immune system 320
The intestinal mucosal immune system 328
Autoimmunity and oral tolerance 332
Gastrointestinal inflammation 333
Immune cell trafficking and adhesion molecules 334
Leukocyte chemotaxis and activation 336
Cytokines 338
Lipid mediators of inflammation 339
Nitric oxide 341
Intestinal epithelial cells 341
Host–microbial interactions shape mucosal immune responses 344
Mast cells 345
Immune-mediated gastrointestinal and liver diseases 345
Eosinophilic esophagitis 345
Autoimmune gastritis 346
Peptic ulcer disease and Helicobacter pylori 346
Inflammatory bowel disease 347
Celiac disease 347
Autoimmune pancreatitis 348
Autoimmune liver diseases 348
Further reading 350
CHAPTER 18: Epithelia and gastrointestinal function 351
Organization of the gut wall 351
Organization of epithelial cells and sheets 352
Initiation of epithelial polarization 353
Structure of intercellular junctions 354
Polarized protein delivery 355
Maintenance of membrane domains 355
Organization of the cytoskeleton 356
Basement membrane 356
Mucosal barriers 356
Extrinsic barriers 357
Intrinsic barriers 358
Water movement across the epithelial barrier 360
Epithelial barrier and disease 360
Epithelial renewal 360
Regulation of barrier function by physiological stimuli 360
Dysregulation of epithelial barrier function 361
Contributions of barrier loss to immune-mediated disease 361
Interactions of epithelial and immune cells 362
Integration of mucosal function 363
Further reading 363
B Motility 364
CHAPTER 19: Esophageal motor function 364
Pharynx and upper esophageal sphincter 364
Anatomy and function 364
Mechanics of oropharyngeal swallowing 367
Esophagus 370
Anatomy and function 370
Mechanics of esophageal peristalsis 371
Control of esophageal peristalsis 373
Esophagogastric junction 375
Anatomy and function 375
Esophagogastric junction opening 377
Further reading 380
CHAPTER 20: Gastric motility and gastric emptying 382
Orientation of gastric smooth muscle fibers 382
Innervation of the gastric smooth muscle 382
Efferent extrinsic innervation 382
Afferent extrinsic innervation 384
Intrinsic innervation of the stomach 384
Regional motor activity in the stomach and coordination with the duodenum 384
Proximal stomach 384
Distal stomach 386
Pylorus 390
Duodenum and small intestine control of gastric emptying 392
Gastric emptying 392
Gastric emptying of liquids 392
Gastric emptying of digestible solids 394
Gastric emptying of fats 396
Gastric emptying of indigestible solids 396
Intragastric distribution of solids and liquids 396
Extrinsic regulation of gastric emptying 397
Further reading 400
CHAPTER 21: Motility of the small intestine and colon 401
Anatomic and functional considerations 401
Small intestinal and colonic transit 402
Specialized small intestinal and colonic cell types 403
Smooth muscle 403
Nervous tissues 403
Interstitial cells of Cajal 404
ICC in disease 405
Interaction between extrinsic and enteric nervous system 405
Coupling of small intestinal and colonic contractions 407
Control of small intestinal and colonic peristalsis 407
Stereotypical motor patterns 408
Small intestine 408
Colon 412
Sphincteric motor function 413
Ileocolonic junction 413
Anus and pelvic floor 414
Rectum and anal canal 415
Extended reflexes involving the small intestine and colon 415
Intestinointestinal reflex 415
Nutrient-evoked small intestinal reflexes 415
Colocolonic reflexes 416
Rectoanal inhibitory reflex 416
Other small intestinal and colonic reflexes 416
External influences on motor activity 416
Motor function during sleep 416
Central nervous system modulation 417
Immune and inflammatory modulation 418
Further reading 419
CHAPTER 22: Motility of the biliary tract 420
Gallbladder 420
Neurobiology 420
Gallbladder smooth muscle cells 422
Gallbladder interstitial cell of Cajal-like cells 423
Gallbladder emptying 423
Gallbladder filling 425
Sphincter of Oddi 426
Neurobiology 426
Sphincter of Oddi smooth muscle 426
Interprandial sphincter of Oddi activity 427
Pathophysiology of biliary tract motility 428
Mechanisms of biliary stasis in cholesterol disease 428
Inflammation and gallbladder dysmotility 429
Interrelationship between inflammation and gallbladder muscle dysfunction in the development of gallstone disease 431
Overview 431
Further reading 432
C Secretion and absorption 433
CHAPTER 23: Gastric secretions 433
Functional anatomy of the stomach 433
Innervation of the stomach 434
Blood supply to the stomach 434
Gastric cells (see Chapter 4) 435
Mucous cells 435
Parietal cells 436
Histamine-producing cells 436
Chief cells 436
Endocrine cells 437
Gastric acid secretion 437
Pathways involved in acid secretion 437
Parietal cell transport of hydronium ions 438
Central nervous involvement in gastric acid secretion 439
Measurement of gastric acid secretion 439
Basal acid secretion 440
Meal-stimulated acid secretion 440
Cephalic phase of acid secretion 440
Gastric phase of acid secretion 441
Intestinal phase of acid secretion 441
Feedback inhibition of acid secretion 441
Pharmacology of parietal cell receptors 442
Histamine receptors 442
Muscarinic receptor and its antagonists 442
Gastrin receptor and its antagonists 443
Miscellaneous receptors on the parietal cell 443
Signaling pathways involved in gastric acid secretion 443
Calcium-, cyclic AMP-, and protein kinase C-mediated stimulation of gastric acid secretion 443
Sonic hedgehog signal transduction pathway 444
Parietal cell H+,K+-adenosine triphosphatase 444
Other secretory products 447
Mucus 447
Bicarbonate 448
Pepsinogen 449
Histamine 449
Intrinsic factor 449
Prostaglandins 450
Nitric oxide 451
Regulatory peptide secretion in the stomach 451
Gastrin 451
Somatostatin 452
Gastrin-releasing peptide (GRP) 452
Ghrelin 453
Further reading 453
CHAPTER 24: Electrolyte secretion and absorption in the small intestine and colon 454
Introduction 454
The intestinal epithelium 455
Functional polarity 455
Tight junctions 456
Epithelial organization and diversity 457
Principles of epithelial transport 458
Transepithelial transport 458
Types of transmembrane transport 458
Fluid transport 459
Molecular mechanisms of water transport 459
Electrolyte transport proteins 459
ATPase pumps 460
Exchangers and cotransporters 460
Ion channels 464
Transepithelial electrolyte transport 465
Electrolyte absorptive mechanisms 466
Electrolyte secretory mechanisms 468
Regulation of fluid and electrolyte transport 470
Intracellular regulatory mechanisms 470
Intercellular regulatory mechanisms 475
Neural regulation 478
Interactions between intercellular regulatory mechanisms 478
Disorders of electrolyte transport 479
Genetic defects in electrolyte absorptive processes 479
Genetic defects in electrolyte secretory mechanisms 480
Other relevant genetic disorders 481
Mechanisms underlying other conditions associated with defective fluid and electrolyte transport 481
Conclusions 482
Further reading 483
CHAPTER 25: Pancreatic secretion 484
Formation and composition of pancreatic juice 484
Water and electrolytes 485
Enzymes 486
Other biological substances 489
Stimulation of pancreatic secretion 489
Hormonal mechanisms 489
Other hormones and stimulatory factors 492
Neural mechanisms 493
Intracellular control of pancreatic secretion 495
Receptors 495
Transmembrane signaling 496
Intracellular messengers 497
Inhibition of pancreatic secretion 502
Inhibitory phase of pancreatic secretion 502
Feedback regulation of pancreatic secretion 504
Patterns of secretion 505
Basal secretion 505
Prandial and postprandial secretion 505
Further reading 507
CHAPTER 26: Bile secretion and cholestasis 508
Introduction 508
Bile composition 508
Bile acids 508
Phospholipids and cholesterol 509
Proteins 510
Bilirubin 510
Electrolytes 510
Nucleotides 510
Heavy metals 510
Other 510
Anatomy and physiology of the bile secretory unit 510
Hepatocyte 511
Cholangiocyte 512
Gallbladder 512
Enterohepatic circulation 512
Cholehepatic shunt 513
Mechanisms of bile formation 513
Principles of membrane solute and ion transport 514
Bile acid-dependent bile formation 515
Bile acid-independent bile flow 519
Ductular bile formation 519
Regulation of bile formation 522
Regulation of canalicular bile formation 522
Regulation of ductular secretion 524
Mechanisms of cholestasis 526
Cholestatic liver disease 526
General cellular mechanism of cholestasis 526
Hereditary cholestasis syndromes 527
Dubin–Johnson 528
Bile acid synthesis defects 528
Defects of ductular transport 529
Disorders of bile duct development 529
Summary 530
Further reading 530
D Nutrition 531
CHAPTER 27: General nutritional principles 531
Basic nutritional principles 531
Body composition 531
Diet for healthy people 531
Energy metabolism 538
Proteins 540
Lipids 542
Carbohydrates 544
Fiber 545
Micronutrients: minerals and vitamins 547
Altered nutritional states 558
Starvation 558
Metabolic response to illness and injury 559
Further reading 560
CHAPTER 28: Control of appetite/satiety and energy balance 562
Key hormones that regulate energy balance 563
Leptin 563
Ghrelin 565
The arcuate nucleus of the hypothalamus and the central melanocortin system 566
Hypothalamic control of glucose homeostasis 567
Single-minded 1 (SIM1) 569
Ventromedial hypothalamic neurons (VMH) 569
VMH neurons control of glucose and energy homeostasis 569
The role of the vagus nerve in regulating food intake and energy balance 569
Serotonin regulates food intake and body weight 570
Perspectives 571
Further reading 571
CHAPTER 29: Nutrient digestion, absorption, and sensing 572
Digestion of carbohydrates, proteins, and lipids 572
Digestion of carbohydrates 572
Digestion of proteins 575
Digestion of lipids 577
Absorption of carbohydrates, proteins, and lipids 578
Absorption of carbohydrates 578
Absorption of proteins 580
Absorption of lipids 582
Nutrient sensing 583
5? adenosine monophosphate-activated protein kinase 583
Sensing of amino acids and the GCN2/ATF4 pathway 585
Global regulation of cellular state and mTOR 586
Conclusions 589
Further reading 589
CHAPTER 30: Vitamins and minerals 590
Introduction 590
Water-soluble vitamins 590
Thiamin (B-1) 590
Riboflavin (B-2) 591
Niacin (B-3) 593
Pyridoxine (vitamin B-6) 593
Cobalamin (vitamin B-12) 593
Folate 596
Vitamin C 598
Fat-soluble vitamins 600
Vitamin A 600
Vitamin D 602
Vitamin E 605
Vitamin K 606
Minerals 607
Calcium 607
Magnesium 611
Iron 613
Zinc 615
Copper 617
Chromium 618
Selenium 619
Further reading 620
E Miscellaneous 621
CHAPTER 31: Neoplasia of the gastrointestinal tract 621
Introduction 621
The cancer genome 621
Drivers versus passengers 622
Targeting oncogenes and tumor suppressor genes 622
Intratumor heterogeneity 622
The fallacy of the “magic bullet” concept in solid cancers 622
Sustaining proliferative signaling 623
The epidermal growth factor receptor pathway 623
The KRAS-BRAF-MEK-ERK pathway 623
The PI3K-AKT-mTOR pathway 625
HER2 626
The Wnt-?-catenin pathway 626
Evading growth suppressors 628
The p53 pathway 628
The retinoblastoma pathway 629
Contact inhibition 630
The transforming growth factor-? pathway 630
Genetic and epigenetic instability 631
Chromosomal instability 632
Microsatellite instability 632
CpG island methylation phenotype 633
Subtypes of colorectal carcinoma based on gene expression profiling 634
Pancreatic cancer and BRCA 634
Telomeres and telomerase – enabling replicative immortality 634
Telomeres 634
Oncogene-induced telomeric damage 635
Telomerase enables replicative immortality 635
Telomerase patterns of expression in normal and cancer cells 635
Mechanisms for telomerase reactivation or overexpression 636
TERT-deficient mice 636
Proposed models for telomeres, telomerase, and cancer 636
Telomere length and cancer risk 637
Telomerase-targeted therapy 637
Cancer stem cells – a shifting paradigm 637
Cancer stem cell markers 637
Cancer stem cells are responsible for tumor recurrence 637
Cancer stem cells and metastasis 638
Cancer stem cells give rise to differentiated tumor cells 638
Cancer stem cells give rise to stromal cells 638
Wnt-?-catenin, Lgr5+ cancer stem cells and telomerase 638
Cancer stem cells found in intact benign and malignant lesions 639
Cancer stem cells and the cells of origin 639
Uni- or bidirectional hierarchy of tumor cells 639
Clonal evolution and the cancer stem cells hypotheses 639
Cancer stem cells targeted therapy 640
Invasion and metastasis 640
Steps in the metastatic process 640
Local invasion and the epithelial–mesenchymal/mesenchymal–epithelial transition hypothesis 641
The role of the microenvironment in promoting local invasion 642
Survival in the circulation 642
Circulating tumor cells 643
Homing 644
Extravasation 645
Survival in the microenvironment 645
Dormancy and disseminated tumor cells 645
Evolution and timing of metastasis 646
Intermetastatic heterogeneity 647
Inflammation and cancer 647
Inflammatory cells are part of the tumor microenvironment 647
Chronic inflammation predisposes to cancer 648
Nonsteroidal antiinflammatory drugs can reduce colorectal adenoma recurrence 648
Aspirin can reduce cancer incidence 649
Aspirin can reduce cancer mortality 649
Mechanism underlying the effect of aspirin on cancer incidence and mortality 649
Future clinical trials 649
Further reading 650
CHAPTER 32: The human intestinal microbiota and microbiome 651
Introduction 651
Describing microbes 651
Molecular phylogenetics in gut microbial ecology 652
Names and designations for bacteria 652
Methods for community composition 653
The microbiota of the human GI tract 653
Large-scale human microbiome studies 653
The Human Microbiome Project 653
Enterotypes 653
Bacterial inhabitants of the gut 654
Nonbacterial members of the gut 655
Factors that influence the composition of the gut microbiota 656
Pregnancy 656
Age 656
Diet 657
Antibiotics 658
Host genetics, the microbiome, and their interaction in disease 658
Twins studies 658
Diseases with a genetic basis also associate with altered microbiota 658
Adaptive immunity 658
Metabolism 658
Therapeutic approaches to modulating the gut microbiota 659
Fecal transplantation (bacteriotherapy) 659
Probiotics and prebiotics 659
Prospectus 659
Further reading 659
CHAPTER 33: Drug metabolism, transport, and pharmacogenomics 660
General principles 660
Phase I drug metabolism 660
Sites of CYP-mediated drug metabolism 661
CYP enzymes 661
Flavin monooxygenases 663
Phase II drug metabolism 663
UDP-glucuronosyltransferases 663
Glutathione-S-transferases 664
Sulfotransferases 665
N-acetyltransferases 665
Thiopurine methyltransferase 665
Transport proteins 665
Uptake transporters 666
Efflux transporters 668
Transporter regulation 669
Transporter pharmacogenetics 670
Transporter-mediated drug interactions 670
Further reading 671
PART 3: Principles of clinical gastroenterology 673
CHAPTER 34: Clinical decision making 675
Introduction 675
Systematic reviews and metaanalysis 675
Cost effectiveness and medical decision making 676
Forms of economic analysis 677
Costs 677
Evidence-based approach to economic studies 678
Validity of the methods 678
Presentation of the results 679
Implications for patient care 679
Clinical practice guidelines 680
Developing a guideline using GRADE 681
Problems implementing guidelines into clinical practice 681
Bridging the gap between evidence and practice: clinical decision support tools and mobile health 682
Definition of mobile health 682
Current uses of mobile health for clinical decision making 682
Advantages of mobile health 683
Evidence for the use of mobile health for clinical decision making 683
Current barriers to mobile health 683
Conclusions 684
Further reading 684
CHAPTER 35: Approach to the patient with dyspepsia and related functional gastrointestinal complaints 685
Definitions 685
Etiologies and pathophysiology 686
Organic causes of dyspepsia 686
Functional dyspepsia 687
Diagnosis 687
Differential diagnosis 688
Principles of management 688
Management of uninvestigated dyspepsia 688
Management of functional dyspepsia 689
Further reading 690
CHAPTER 36: Approach to the patient with dysphagia, odynophagia, or noncardiac chest pain 691
Definition 691
Dysphagia 691
Odynophagia 691
Chest pain 691
Organic versus functional disorders 692
Pathophysiology 692
Dysphagia 692
Odynophagia 692
Noncardiac chest pain 692
Etiologies 693
Dysphagia 693
Odynophagia 693
Chest pain 694
Diagnosis 694
History and physical examination 694
Laboratory tests 694
Imaging tests 694
Function tests 695
Differential diagnosis 695
Principles of management 695
Management of dysphagia 695
Management of odynophagia 697
Management of noncardiac chest pain 698
Further reading 699
CHAPTER 37: Approach to the patient with unintentional weight loss 700
Introduction 700
Definition 700
Pathophysiology 700
Cancer-related cachexia and altered lipid metabolism 701
Cytokines and cachexia 701
Etiology 701
Diagnosis 702
History and physical examination 703
Laboratory tests 704
Imaging tests 705
Differential diagnosis 706
Malignancy 706
Endocrine disorders 707
Gastrointestinal diseases 707
Human immunodeficiency virus and other chronic infections 707
Cardiopulmonary disease 707
Chronic obstructive pulmonary disease 707
Renal disease 707
Neurological diseases 707
Inflammatory disorders 707
Psychiatric disorders 708
Drugs 708
Substance abuse 708
Principles of management 708
Further reading 709
CHAPTER 38: Approach to the patient with nausea and vomiting 710
Definitions 710
Etiologies and pathophysiology 711
Medications 711
Chemotherapy (and radiation therapy) induced nausea and vomiting (CINV) 712
Infectious causes 712
Mechanical obstruction and intraperitoneal inflammation 712
Gastroparesis and chronic intestinal pseudoobstruction 713
Cyclic vomiting syndrome (CVS) 713
Chronic idiopathic nausea and functional vomiting 715
Rumination syndrome 715
Nausea and vomiting of pregnancy (NVP) 716
Postoperative nausea and vomiting (PONV) 716
Causes involving the central and peripheral nervous systems 716
Miscellaneous conditions 717
Diagnosis and differential diagnosis 717
Historical features 718
Physical examination findings 719
Laboratory testing 719
Endoscopic and imaging evaluation 719
Studies of gastrointestinal motor function 719
Principles of management 721
Indications for hospitalization 721
Dietary and nonmedicinal considerations 721
Medications for nausea and vomiting 721
Management approaches in selected clinical settings 724
Future treatments of nausea and vomiting 727
Further reading 727
CHAPTER 39: Approach to the patient with abdominal pain 729
Background and importance 729
The neurobiology of pain 729
Anatomical pathways 729
The cellular, molecular, and neurochemical substrate of pain 734
Clinically important physiological characteristics of visceral nociception 735
Classification of abdominal pain 741
Clinical assessment of the patient with abdominal pain 742
History 742
Physical examination 743
Differential diagnosis 744
Diagnostic work-up 747
Approach to treatment 747
Pharmacological management of chronic pain 748
Neural blockade and neuorolytic therapy 751
Nonconventional methods of chronic abdominal pain treatment 752
Recognition and management of special abdominal pain syndromes 752
Functional abdominal pain syndrome 754
Conclusions 755
Further reading 756
CHAPTER 40: Approach to the patient with gas and bloating 757
Introduction 757
Definitions 757
Pathophysiology/etiology of bloating and gas 757
Sources and composition of gastrointestinal gas 757
Pathophysiology of bloating 759
Pathophysiology of gas/flatulence 760
Diagnosis 760
History and physical examination 760
Diagnostic tests 761
Differential diagnosis and principles of management 764
Carbohydrate intolerances/malabsorption 764
Small intestinal bacterial overgrowth 766
Intestinal microbiome, probiotics, and prebiotics 767
Dysmotility and dyssynergic defecation/constipation 767
Management of flatulence 767
Conclusion 767
Acknowledgment 768
Further reading 768
CHAPTER 41: Approach to the patient with diarrhea 769
Introduction 769
Acute diarrhea 769
Epidemiology 769
Causes 770
Diagnostic approach 774
Treatment 776
Complications of acute diarrheal diseases in adults 776
Chronic diarrhea 776
Definition, classification, and epidemiology 776
Clinical evaluation of chronic diarrhea 778
Secretory diarrhea 779
Osmotic diarrhea 782
Malabsorptive diarrhea 783
Inflammatory diarrhea 784
Prolonged infectious diarrhea 787
Nosocomial diarrhea 787
Functional diarrhea 789
Congenital and neonatal diarrhea 790
Further reading 790
CHAPTER 42: Approach to the patient with constipation 791
Definition 791
Epidemiology 791
Populations at higher risk of constipation 791
Familial tendency and other comorbid features 792
Economic and social impact 792
Psychological distress, abuse, and impact on quality of life 793
Etiology, subtypes, and pathophysiology of chronic constipation 794
Pathophysiology of slow-transit constipation 795
Pathophysiology of evacuation disorders 796
Pathophysiology of constipation-predominant irritable bowel syndrome 798
Clinical evaluation of chronic constipation 798
Medical history 798
Physical examination 798
Diagnostic tests 799
Radiographic studies 800
Endoscopy 800
Specific diagnostic tests for functional constipation 800
Conclusions on diagnostic testing 805
Treatment of chronic constipation 806
Lifestyle changes, fluid intake, and exercise 806
Treatment of drug-induced constipation 806
Diet and fiber 806
Pharmacological treatments 808
Treatment of evacuation disorders 811
Surgical treatment 812
Sacral nerve stimulation 813
Management of Hirschsprung disease 813
Management of fecal impaction 813
Complications of constipation 813
Further reading 813
CHAPTER 43: Approach to the patient with acute abdomen 815
Definitions 815
Pathophysiology 815
Neuroanatomy 815
Etiologies 818
Diagnosis 818
History 818
Physical examination 822
Special populations 824
Development of acute abdominal pain in the hospitalized patient 825
Diagnostic evaluation 825
Differential diagnosis 830
Principles of management 830
Empiric management and when to refer 830
Further reading 830
CHAPTER 44: Approach to the patient with gastrointestinal bleeding 831
Introduction 831
General assessment 832
History 832
Physical examination 832
Laboratory studies 832
Clinical determination of the bleeding site 832
Hospitalization 833
Resuscitation 833
Initial medical therapy 833
Diagnostic and therapeutic modalities 833
Endoscopy 833
Endoscopic hemostasis 834
Radiological intervention and nuclear studies 835
Surgery 836
Causes of upper gastrointestinal bleeding 836
Epidemiology 836
Risk stratification 836
Peptic ulcer (see Chapter 56) 837
Ulcer hemorrhage in hospitalized patients 841
Esophagitis (see Chapter 49) 841
Mallory–Weiss tears (see Chapter 54) 842
Cameron lesions 842
Angiodysplasia and gastric antral vascular ectasia (see Chapter 127) 842
Portal hypertensive gastropathy 843
Hemobilia and hemosuccus pancreaticus 843
Aortoenteric fistula 843
Varices (see Chapter 138) 843
Lower gastrointestinal or colonic bleeding 845
Diagnostic approach 845
Colonoscopy 845
Flexible sigmoidoscopy 846
Anoscopy 846
Angiography 846
Computed tomography 846
Surgery 846
Colon polyps and cancer 848
Vascular ectasia 848
Internal hemorrhoids 849
Anal fissures 849
Rectal varices 849
Rectal ulcers 849
Obscure gastrointestinal bleeding 849
Diagnostic tools 850
Approach to the patient with overt obscure gastrointestinal bleeding 851
Further reading 852
CHAPTER 45: Approach to the patient with abnormal liver chemistries or jaundice 853
Introduction 853
Definition and pathophysiology 853
Clinical use of liver function tests 854
Patterns of liver injury 856
Clinical assessment of disease severity 857
Etiologies and risk factors for common liver diseases 857
Diagnosis and physical examination 859
Common clinical presentations of liver injury 860
Chronic liver disease 865
Further reading 867
CHAPTER 46: Approach to gastrointestinal and liver diseases in pregnancy 868
Introduction 868
Oral cavity 868
Upper gastrointestinal tract 870
Gastroesophageal reflux disease 870
Peptic ulcer disease 871
Nausea and vomiting of pregnancy and hyperemesis gravidarum 871
Epidemiology 871
Disorders of the intestinal tract 874
Celiac disease 874
Irritable bowel syndrome 874
Constipation 874
Diarrhea 875
Abdominal pain 876
Inflammatory bowel disease 876
Biologics 878
Anorectal and perineal disorders 878
Endoscopy in pregnancy 880
Approach to liver diseases in pregnancy 880
Liver physiology during pregnancy 880
Diagnostic testing during pregnancy 881
Liver diseases unique to pregnancy 881
Acute fatty liver disease of pregnancy (AFLP) 884
Epidemiology 884
Presentation 884
Pathogenesis 885
Liver diseases that can be exacerbated by pregnancy 885
Acute pancreatitis 886
Budd-Chiari syndrome (BCS) 886
Liver disease coincident with pregnancy 887
Intercurrent hepatobiliary disease 887
Hepatitis C (HCV) 889
Pregnancy and liver transplantation 891
Further reading 892
CHAPTER 47: Genetic counseling for gastrointestinal patients 893
Structure and function of nucleic acids 893
Functional anatomy of the human genome 893
Methods used to detect mutations 894
Key terms in genetics 895
Inheritance patterns 895
Genetic mechanisms in disease causation 897
Diseases in gastroenterology with genetic counseling/genetic testing implications (see Chapter 123) 898
Inherited gastrointestinal cancer and polyposis syndromes (see Chapter 79) 898
Nonmalignant GI disorders 903
Liver disorders 903
Principles of genetic counseling 905
Indications 905
How to provide genetic counseling 905
Obtaining a genetic/family history 905
Risk assessment and medical management 907
Approach to patients 907
Informed consent 908
Duty to privacy and duty to warn relatives 908
GINA 908
Family planning 908
Genomics, future trends, and challenges 909
Total genomic sequencing 909
Direct to consumer testing 909
Dealing with variants of uncertain significance (VUS) 909
Nonpaternity or paternal misattribution 909
Desire not to know 910
Genetic testing in children 910
Additional resources 910
PART 4: Gastrointestinal diseases 911
A Esophagus 913
CHAPTER 48: Motility disorders of the esophagus 913
Oropharyngeal swallowing disorders 913
Mechanics of oropharyngeal swallowing 913
Evaluation and classification of oropharyngeal dysphagia 915
Structural etiologies of oropharyngeal dysphagia 916
Functional etiologies of oropharyngeal dysphagia 917
Management of oropharyngeal dysphagia 919
Esophageal motility disorders 920
Esophageal motor function 920
Evaluation and classification of esophageal dysphagia 923
Diagnostic testing in esophageal disease 923
Achalasia 929
Spastic disorders 934
Hypercontractility 937
Hypocontractile motility 938
Esophageal involvement in systemic disease 938
Scleroderma 938
Other collagen vascular and connective tissue diseases 939
Diabetes mellitus 939
Acknowledgment 939
Further reading 939
CHAPTER 49: Gastroesophageal reflux disease 940
Definitions and epidemiology 940
Histopathology of esophagitis 941
Pathogenesis 942
Mechanisms of reflux 942
Delayed gastric emptying 945
Esophageal clearance 945
Tissue resistance 946
Clinical presentation and natural history 946
Typical reflux symptoms 947
Atypical symptoms 947
Natural history 949
Differential diagnosis 949
Associated conditions 949
Diagnostic evaluation 950
Clinical evaluation and empiric trials 950
Endoscopy 951
Reflux identification: esophageal pH-metry and pH-impedance-metry 952
Other investigations 955
Summary 956
Therapeutic management 956
Lifestyle modifications 956
Antacids 957
Acid suppression 957
Reflux inhibition 959
Prokinetic drugs 959
Targeting visceral hypersensitivity 960
Surgical fundoplication 960
Novel antireflux procedures 961
Management of GERD complications: peptic strictures 961
Further reading 962
CHAPTER 50: Eosinophilic esophagitis 963
Introduction 963
Epidemiology 963
Eosinophil biology 964
Pathophysiology 964
Diagnosis 965
Esophageal motility and distensibility 967
Treatment 967
Potential directions for future targeted therapy 968
Prognosis for eosinophilic esophagitis 969
Conclusion 970
Further reading 970
CHAPTER 51: Esophageal infections and disorders associated with acquired immunodeficiency syndrome 971
Introduction 971
Epidemiology and predisposing factors 971
Fungal infections 972
Candida species 972
Other fungi 975
Viral infections 975
Herpes simplex virus 975
Cytomegalovirus 977
Other viruses 979
Mycobacterial infections 979
Epidemiology 979
Pathology 979
Clinical manifestations and complications 979
Diagnosis 979
Treatment 980
Bacterial infections 980
Epidemiology 980
Pathology 980
Clinical manifestations and complications 980
Diagnosis 980
Treatment 980
Protozoal infections 980
Specific HIV-related esophageal disorders 980
Disorders associated with primary HIV infection 981
Idiopathic esophageal ulcer 981
Neoplasms associated with AIDS 981
Further reading 982
CHAPTER 52: Barrett esophagus and esophageal adenocarcinoma 983
Introduction 983
Diagnostic criteria for Barrett esophagus 983
Cardiac mucosa in the esophagus 985
Intestinal metaplasia at the GEJ 985
Epidemiology of Barrett esophagus 986
Epidemiology of esophageal adenocarcinoma 986
Cancer risk in Barrett esophagus 987
Pathogenesis of metaplasia in the esophagus 987
Physiological perturbations 987
Exposure to noxious agents 987
Cells of origin for Barrett metaplasia 988
Molecular biology of dysplasia and adenocarcinoma in Barrett esophagus 989
Proliferation without exogenous stimulation 989
Resistance to growth-inhibitory signals 990
Avoidance of apoptosis 990
Resistance to cell senescence 991
Development of new vascular supplies (angiogenesis) 991
Invasion and metastasis 991
Enabling characteristics of cancer cells 992
Dysplasia in Barrett esophagus 992
Endoscopic perspectives 992
Histopathological perspectives 993
Management of patients with Barrett esophagus 994
Treatment of GERD in Barrett esophagus 994
Endoscopic surveillance for dysplasia 995
Treatment of dysplasia in Barrett esophagus 996
Unresolved issues regarding endoscopic ablative therapy 999
Role of NSAIDs in prevention of cancer in Barrett esophagus 1000
Management recommendations 1001
Adenocarcinoma of the esophagus 1001
Clinical suspicion for esophageal cancer 1001
Natural history 1001
Staging systems 1002
Staging studies 1002
Treatment summary 1003
Esophagectomy 1003
Radiation therapy 1003
Treatment of stage IA cancer 1003
Surgical candidates with stage IB-stage IIIC cancer 1004
Definitive chemoradiation 1004
Neoadjuvant radiation therapy 1004
Neoadjuvant chemotherapy 1005
Neoadjuvant chemoradiation 1005
Perioperative chemotherapy 1005
Adjuvant therapy 1006
Induction chemotherapy 1006
Assessing response to treatment 1006
Treatment of metastatic disease 1006
Phase III trials in metastatic disease 1007
Molecularly-targeted therapy 1007
Refractory disease 1008
Treatment recommendations 1008
Further reading 1008
CHAPTER 53: Esophageal squamous cell carcinomas and other neoplasms 1009
Definition 1009
Epidemiology and risk factors 1009
Tobacco and alcohol 1009
Diet and nutrition 1010
Achalasia 1010
Head and neck squamous cell carcinoma 1010
Tylosis 1010
Other factors 1010
Temporal/secular trends 1011
Geographic variation 1011
Pathogenesis 1011
Clinical presentation and natural history 1012
Differential diagnosis 1012
Benign epithelial tumors (squamous cell papilloma) 1012
Other malignant epithelial tumors 1012
Benign nonepithelial tumors 1013
Malignant nonepithelial tumors 1014
Management and therapy 1015
Diagnostic evaluation 1015
Staging and staging systems 1015
Therapy for esophageal SCC 1017
Complications 1021
Prevention 1022
Screening 1022
Ingestible esophageal capsule endoscopy and transnasal endoscopy 1022
Further reading 1022
CHAPTER 54: Miscellaneous diseases of the esophagus: foreign bodies, physical injury, and systemic and dermatological diseases 1023
Introduction 1023
Esophageal trauma 1023
Mallory–Weiss syndrome (see Chapter 44) 1023
Esophageal perforation and rupture 1024
Esophageal intramural hematomas 1025
Esophageal foreign bodies 1026
Epidemiology 1026
Pathogenesis 1026
Presentation 1026
Diagnosis 1026
Treatment 1027
Pill esophagitis 1028
Epidemiology 1028
Pathogenesis 1028
Presentation 1028
Diagnosis 1029
Treatment 1029
Corrosive esophagitis 1029
Epidemiology 1029
Pathogenesis 1030
Presentation 1030
Diagnosis 1030
Treatment 1031
Acute esophageal necrosis 1031
Epidemiology 1031
Pathogenesis 1031
Presentation 1031
Diagnosis 1031
Treatment 1031
Lymphocytic esophagitis 1032
Epidemiology 1032
Pathogenesis 1032
Presentation 1032
Diagnosis 1033
Treatment 1033
Systemic diseases 1033
Sarcoidosis 1033
Crohn’s disease 1033
Graft-versus-host disease 1034
Behçet syndrome 1034
Miscellaneous autoimmune diseases 1035
Dermatological diseases 1035
Pemphigus vulgaris 1035
Bullous pemphigoid 1036
Benign mucous membrane pemphigoid 1036
Epidermolysis bullosa dystrophica 1036
Further reading 1038
B Stomach 1039
CHAPTER 55: Disorders of gastric emptying 1039
Delayed gastric emptying (gastroparesis) 1039
Symptoms and clinical presentation 1039
Evaluation of patients with suspected gastroparesis 1040
Evaluation of gastric emptying, motor function, myoelectric activity, and radiographic contrast techniques 1041
Gastroparesis and disorders with delayed gastric emptying 1045
Other disorders associated with delayed gastric emptying 1047
Treatment of symptomatic gastroparesis 1052
Refractory gastroparesis 1056
Disorders with rapid gastric emptying 1059
Postsurgical dumping syndrome 1059
Other disorders with rapid gastric emptying 1060
Functional dyspepsia 1061
Definition 1061
Pathogenesis with emphasis on gastric dysmotility 1062
Treatment of functional dyspepsia 1063
Summary 1065
Further reading 1065
CHAPTER 56: Peptic ulcer disease 1066
Introduction 1066
Definition 1066
Ulcer locations 1066
Etiology 1067
H. pylori 1067
Nonsteroidal antiinflammatory drugs 1067
Non-H. pylori, non-NSAID 1068
Idiopathic 1069
Epidemiology 1071
Temporal trends 1071
Demographic trends 1071
Ulcer incidence and prevalence 1071
Geographical trends 1071
Trends in hospitalization, mortality, and complications 1072
Epidemiology of Helicobacter pylori 1072
Epidemiology of NSAID use 1074
Epidemiology of non-H. pylori, non-NSAID ulcers 1075
Risk factors 1075
Risk factors – true, false, context-dependent, and unclear 1076
Disease associations and comorbid ulcers 1076
Pathogenesis 1077
Injurious agents – acid and pepsin 1077
Protective mucosal defense 1078
Duodenal ulcers 1078
Gastric ulcers 1079
The pathogenesis of H. pylori induced peptic ulcer disease 1079
Mechanisms of H. pylori induced duodenal and gastric ulceration 1079
Why only some people infected with H. pylori develop peptic ulcer disease 1079
The pathogenesis of NSAID/aspirin-induced PUD 1081
The pathogenesis of non-H. pylori, non-NSAID ulcers 1082
Genetics of peptic ulcer disease 1082
Natural history 1082
Clinical presentation and differential diagnosis 1083
Presentation with dyspepsia 1083
Clinical features of uncomplicated peptic ulcer disease 1085
Clinical features of complicated peptic ulcer disease 1085
Special scenarios – other clinical or endoscopic findings 1086
Therapy and management 1086
Uninvestigated dyspepsia 1086
Identification of ulcer 1090
Treatment of peptic ulcer disease 1090
Identification of specific causes of PUD 1091
Treatment of specific causes of PUD 1095
Recurrent and refractory ulcers 1102
Prevention 1104
Prevention of NSAID and aspirin ulcers 1104
Complications 1108
Hemorrhage 1108
Perforation and penetration 1109
Gastric outlet obstruction 1110
Acknowledgments 1111
Further reading 1111
CHAPTER 57: Zollinger–Ellison syndrome 1112
Introduction 1112
Epidemiology 1113
Pathophysiology 1113
Pathology and classification 1113
Tumor biology 1116
Molecular pathogenesis 1117
Clinical presentation and features 1118
General clinical features 1118
Specific clinical features in MEN1/ZES 1119
Diagnosis and differential diagnosis 1120
Tumor localization 1124
Treatment (not advanced/metastatic disease) 1125
General 1125
Control of gastric acid hypersecretion 1126
Surgical 1128
Treatment of advanced metastatic disease 1130
General 1130
Cytoreductive surgery 1130
Liver-directed therapies 1130
Medical treatment 1132
Peptide radioreceptor therapy using radiolabeled somatostatin analogs 1135
Liver transplantation 1135
Further reading 1136
CHAPTER 58: Gastritis and gastropathy 1137
Definition 1137
Classification of gastritis using the Sydney system 1137
Biopsy protocol 1138
Histological features of chronic gastritis 1138
Nonatrophic chronic gastritis 1138
Multifocal atrophic gastritis 1138
Diffuse corporal atrophic gastritis (autoimmune gastritis) 1140
Epidemiology of Helicobacter pylori-induced gastritis 1140
Gastric colonization 1140
Development of H. pylori-induced gastric inflammation 1141
Clinical presentation and natural history 1142
Patterns of H. pylori-induced gastritis and disease outcome 1142
H. pylori virulence factors and gastric injury 1142
Human genetic polymorphisms and development of disease among H. pylori-infected persons 1143
Diagnosis of H. pylori infection 1144
Histological detection of H. pylori 1144
Rapid urease tests 1144
H. pylori culture 1144
Detection of H. pylori-specific DNA sequences in vivo 1145
Urea breath tests 1145
Serological testing for H. pylori 1145
H. pylori stool antigen tests 1145
Therapy and management of H. pylori infection 1146
Infectious gastritis (excluding H. pylori) 1147
Bacteria 1147
Viruses 1147
Fungi 1148
Parasites 1148
Eosinophilic gastritis 1148
Granulomatous gastritis 1148
Autoimmune gastritis 1149
Clinical features and pathogenesis 1149
Endoscopic appearance 1149
Pathological features 1150
Management 1150
Lymphocytic gastritis 1150
Clinical and endoscopic features 1150
Pathological features 1150
Therapy 1151
Collagenous gastritis 1151
Reactive (chemical) gastropathy (NSAID and bile reflux) 1151
Clinical manifestations and pathogenesis 1151
Endoscopic appearance 1151
Histological features 1151
Hemorrhagic gastropathy 1151
Vascular gastropathy 1152
Portal hypertensive gastropathy 1152
Hypertrophic gastropathy 1152
Ménétrier disease 1153
Gastritis of the cardia 1153
Further reading 1154
CHAPTER 59: Tumors of the stomach 1155
Gastric neoplasia 1155
Gastrointestinal stromal tumors 1155
Neuroendocrine tumors 1156
Lymphomas 1156
Gastric adenocarcinoma 1157
Definition 1157
Epidemiology 1157
Pathogenesis 1160
Clinical presentation and natural history 1164
Differential diagnosis (Box 59.6) 1166
Diagnostic methods (Box 59.7) 1167
Therapy and management (Box 59.9) 1170
Complications and palliative treatment (Table 59.1) 1171
Prevention 1173
Summary 1173
Further reading 1174
CHAPTER 60: Miscellaneous diseases of the stomach 1175
Hiatal hernias 1175
Definition and etiology 1175
Clinical presentation 1176
Diagnosis 1177
Therapy and management 1178
Complications 1179
Gastric volvulus 1179
Definitions 1179
Pathophysiology 1180
Clinical presentation 1180
Therapy and management 1181
Complications 1181
Gastric rupture 1181
Definitions 1181
Clinical presentation 1182
Therapy and management 1182
Foreign bodies 1182
Definitions and epidemiology 1182
Clinical presentation and natural history 1182
Therapy and management 1183
Caustic ingestion injury 1183
Definitions and epidemiology 1183
Clinical presentation 1183
Therapy and management 1183
Complications 1184
Gastric bezoars 1184
Definition 1184
Epidemiology 1184
Pathogenesis 1184
Clinical presentation 1185
Therapy and management 1185
Heterotopic pancreas 1186
Squamous cardiac epithelium 1187
Further reading 1187
C Small intestine 1188
CHAPTER 61: Dysmotility of the small intestine and colon 1188
Epidemiology 1189
Neural control of small intestinal and colonic motility (see Chapter 15) 1189
Ontogeny of the enteric nervous system 1190
Migration 1190
Differentiation of neurons 1190
Chronic small intestinal pseudoobstruction 1192
Etiology 1192
Clinical manifestations of small intestinal dysmotility 1211
Diagnostic studies for small intestinal dysmotility 1212
Differential diagnosis between chronic intestinal pseudoobstruction and mechanical obstruction 1216
Treatment 1216
Colonic dysmotility (pseudoobstruction) and megacolon 1218
Interstitial cells of Cajal in maldevelopment and acquired diseases of the colon 1218
Syndromes generally attributed to disorders of colonic motility 1221
Syndromes partly attributed to disorders of colonic motility 1227
Response of the colon to drugs 1228
Further reading 1229
CHAPTER 62: Bacterial, viral, and toxic causes of diarrhea, gastroenteritis, and anorectal infections 1230
Clinical considerations at presentation 1230
Microbiological diagnosis 1230
Adjunct evaluations 1232
Specific therapy 1232
Symptomatic measures 1233
Prevention 1233
Hydration 1233
Syndromic management, including diagnosis and therapy, of community-acquired diarrhea and gastroenteritis 1233
Illnesses in which vomiting predominates 1234
Nonbloody acute diarrhea 1234
Bloody acute diarrhea 1234
Chronic or persistent nonbloody diarrhea 1234
Chronic or persistent bloody diarrhea 1234
Returned traveler, or newly arrived immigrant, with acute or chronic nonbloody diarrhea 1235
Anorectal symptoms 1235
Persistent diarrhea in resource-poor settings 1235
Diarrhea in the immunocompromised 1236
Traveler’s diarrhea 1236
Genetic susceptibility or resistance to infections 1236
Specific agents 1237
Bacterial pathogens 1237
Viral agents of gastroenteritis 1273
Marine intoxications with gastrointestinal effects 1278
Anorectal infections 1280
Summary 1282
Further reading 1282
CHAPTER 63: Chronic infections of the small intestine 1283
Whipple’s disease 1283
Epidemiology 1283
Pathophysiology 1284
Clinical manifestations 1285
Diagnostic evaluation 1285
Differential diagnosis 1287
Treatment 1287
Tropical sprue 1288
Epidemiology 1288
Etiology and pathogenesis 1288
Clinical manifestations and differential diagnosis 1288
Diagnosis and laboratory manifestations 1289
Treatment 1289
Tuberculosis (TB) 1289
Epidemiology 1290
Pathogenesis 1290
Clinicopathological manifestations 1291
Diagnostic evaluation 1291
Pathology 1292
Biomarkers 1292
Differential diagnosis 1292
Treatment and prognosis 1293
Mycotic infections 1294
Histoplasmosis 1294
Aspergillosis 1295
Candidiasis 1296
Mucormycosis 1297
Further readings 1297
CHAPTER 64: Celiac disease 1298
Introduction 1298
Epidemiology 1298
Pathology and pathogenesis: environmental, genetic, immune 1299
Clinical features 1300
Celiac crisis 1300
Diagnostic studies 1300
Other diagnostic tests 1301
Gluten challenge 1302
Treatment 1303
Diet education 1303
Foods to avoid 1304
Nutritional deficiencies of the gluten-free diet 1304
Cost of and access to gluten-free food 1304
Hidden gluten/cross contamination 1304
Monitoring of patients with celiac disease 1304
Nonresponsive celiac disease 1305
Refractory celiac disease 1307
Ulcerative jejunoileitis 1308
Celiac disease and malignancy 1308
Enteropathy-associated T-cell lymphoma 1308
Carcinoma in celiac disease 1309
Future developments: nondietary therapy for celiac disease? 1309
Further reading 1309
CHAPTER 65: Disorders of epithelial transport, metabolism, and digestion in the small intestine 1310
Disorders of carbohydrate metabolism and absorption 1310
Defects of maltase–gluocoamylase 1311
Sucrase–isomaltase deficiency 1311
Lactose intolerance 1312
Glucose–galactose malabsorption 1314
Fructose malabsorption 1314
Fanconi–Bickel syndrome 1315
Disorders of protein metabolism and absorption 1315
Hartnup disease 1316
Lysinuric protein intolerance 1316
Cystinuria 1317
Blue diaper syndrome 1317
Disorders of fat absorption 1317
Abetalipoproteinemia 1318
Hypobetalipoproteinemia 1319
Chylomicron retention disease 1319
Bile acid malabsorption 1319
Disorders of electrolyte transport 1320
Disorders of iron transport 1320
Disorders of copper transport 1321
Disorders of zinc absorption 1322
Congenital chloride diarrhea 1322
Disorders of sodium transport 1323
Disorders of magnesium absorption 1323
Disorders of vitamin absorption 1323
Folate 1323
Vitamin B-12 1324
Water-soluble vitamins 1324
Fat-soluble vitamins 1326
Further reading 1327
CHAPTER 66: Bacterial overgrowth 1328
Definition 1328
Epidemiology and risk factors 1329
Dysmotility 1330
Altered anatomy 1330
Hypochlorhydria 1330
Immune deficiencies 1331
Multifactorial 1331
Relationship to SIBO unclear or undefined 1331
Pathogenesis 1331
Mucosal injury 1332
Luminal competition with host for nutrients 1332
Bacterial metabolism 1332
Clinical presentation and natural history 1332
Diagnosis 1333
Differential diagnosis 1333
Diagnosis by aspiration and culture 1333
Breath tests 1333
Other tests 1335
The therapeutic trial 1335
Therapy and management 1335
Complications 1336
Prevention 1336
Temporal/secular trends 1337
Geographic variation 1337
Conclusions 1337
Further reading 1337
CHAPTER 67: Short bowel syndrome and small bowel transplantation 1339
Etiology 1340
Epidemiology 1340
Relevant anatomy and physiology 1340
Small bowel 1340
Colon 1341
Stomach and pancreaticobiliary 1341
Influence of SBS bowel anatomy on outcome 1342
Intestinal adaptation 1342
Complications 1343
Gastric hypersecretion 1343
Fluid–electrolyte disturbances 1343
Micronutrient deficiencies 1343
Oxalate nephropathy 1344
Metabolic bone disease 1344
Liver dysfunction and cholelithiasis 1344
Small intestinal bacterial overgrowth 1345
d-Lactic acidosis 1345
Management 1345
Oral diet 1346
Oral fluids 1347
Enteral nutrition 1348
Parenteral hydration 1348
Parenteral nutrition 1348
Medications 1349
Trophic factors 1350
Other medications 1351
Nontransplant surgery 1351
PN weaning 1352
Outcomes 1353
Small bowel transplantation 1354
Indications 1354
Types of intestine allografts 1355
Surgical planning 1355
Outcomes 1356
Complications 1357
Costs 1357
Further reading 1357
CHAPTER 68: Tumors of the small intestine 1358
Introduction 1358
Adenocarcinoma 1358
Definition 1358
Epidemiology (risk factors) 1358
Familial adenomatous polyposis (FAP) 1359
Lynch syndrome 1359
Hamartomatous polyposis syndromes 1360
Crohn’s disease 1360
Celiac disease 1360
Pathogenesis (genetics) 1361
Clinical presentation and natural history 1361
Differential diagnosis 1362
Therapy and management 1364
Complications 1364
Prevention 1364
Temporal/secular trends 1365
Geographic variation 1365
Carcinoid tumors 1365
Definition 1365
Epidemiology (risk factors) 1365
Pathogenesis 1365
Clinical presentation and natural history 1366
Differential diagnosis 1368
Therapy and management 1368
Complications 1370
Prevention 1370
Temporal/secular trends 1370
Geographic variation 1370
Gastrointestinal stromal tumors (GISTs) 1370
Definition 1370
Epidemiology (risk factors) 1370
Pathogenesis (genetics) 1371
Clinical presentation and natural history 1371
Differential diagnosis 1372
Therapy and management 1372
Risk stratification 1372
Complications 1374
Prevention 1374
Temporal/secular trends 1374
Geographic variation 1374
Lymphomas 1374
Definition 1374
Epidemiology (risk factors) 1374
Pathogenesis (genetics) 1375
Clinical presentation and natural history 1376
Differential diagnosis 1378
Therapy and management 1378
Complications 1379
Prevention 1379
Temporal/secular trends 1379
Secondary tumors 1379
Further readings 1379
CHAPTER 69: Miscellaneous diseases of the small intestine 1380
Ulcers of the small intestine 1381
Primary (idiopathic) small bowel ulcers 1381
Drug-induced small bowel ulcers 1383
Small bowel ulcers associated with systemic disorders (see Chapter 124) 1386
Diffuse small bowel ulceration and concurrent malabsorption 1387
Drug-induced small bowel disease 1389
Drugs causing ischemia 1390
Drugs causing motility disorders 1392
Drugs causing malabsorption 1393
Chemotherapeutic agents 1393
Necrotizing enterocolitis 1394
Protein-losing gastroenteropathy 1395
Definition 1395
Etiology 1395
Clinical features 1396
Diagnosis 1396
Therapy 1396
Further reading 1397
D Inflammatory bowel disease 1398
CHAPTER 70: Inflammatory bowel diseases: pathogenesis 1398
Serology in inflammatory bowel diseases 1399
Genetics 1400
Genes and pathways 1400
Shared pathogenic mechanisms with other autoimmune diseases 1401
Noncoding variants 1401
Deep sequencing studies and rare variants 1402
Protective variants 1402
Epigenetic alterations 1402
The intestinal epithelial barrier 1402
The immune response 1403
Innate immune response 1404
Adaptive immune response 1405
Role of intestinal vasculature and the enteric nervous system 1406
The gut microbiome 1407
Environmental triggers for inflammatory bowel diseases 1409
Animal models of colitis 1410
Conclusion 1411
Further reading 1411
CHAPTER 71: Ulcerative colitis 1412
Introduction 1412
Epidemiology 1412
Etiology and pathogenesis 1413
Clinical findings and natural history 1413
Clinical manifestations 1413
Disease course 1415
Extraintestinal manifestations 1421
Peripheral arthritis 1421
Axial arthritis 1421
Osteoporosis 1422
Renal complications 1422
Nutritional management 1425
Medical therapy for ulcerative colitis 1425
Aminosalicylates 1425
Antibiotics 1429
Corticosteroids 1429
Immunomodulators 1432
Methotrexate 1434
Cyclosporine and tacrolimus 1435
Antitumor necrosis factor agents 1436
Medical management of ulcerative colitis 1441
Ulcerative proctitis 1442
Ulcerative proctosigmoiditis 1442
Left-sided ulcerative colitis 1443
Pancolitis 1443
Fulminant colitis and toxic megacolon 1444
Complications of ulcerative colitis 1445
Surgical management (see Chapter 73) 1446
Colon cancer, dysplasia, and colonoscopic surveillance 1448
Pregnancy (see Chapter 46) 1450
Ulcerative colitis in childhood and adolescence 1451
Further reading 1451
CHAPTER 72: Crohn’s disease: clinical manifestations and management 1452
Introduction 1452
Epidemiology 1453
Clinical presentation and natural history 1455
Patient history and physical examination 1455
History and physical examination 1459
Natural history 1464
Differential diagnosis 1465
Classification of Crohn’s disease 1466
Biomarkers of disease and activity 1466
Therapy and management 1468
Medical management of Crohn’s disease 1468
Prevention of recurrence of postoperative Crohn’s disease 1478
Complications 1479
Infectious complications of Crohn’s disease 1479
Cancer in Crohn’s disease 1479
Drug monitoring for adverse events 1480
Psychiatric complications 1480
Nutritional complications 1481
Crohn’s disease of the ileal pouch 1481
Pregnancy and lactation in women with Crohn’s disease 1482
Further reading 1483
CHAPTER 73: Surgical treatment of inflammatory bowel disease 1484
Crohn’s disease 1484
Indications for surgery in Crohn’s disease 1484
Crohn’s disease of the stomach and duodenum 1485
Crohn’s disease of the small bowel 1486
Crohn’s disease of the terminal ileum 1488
Crohn’s colitis 1494
Perianal Crohn’s disease 1497
Medical prevention of Crohn’s recurrences 1498
Ulcerative colitis 1500
Indications for surgery 1500
Proctocolectomy with Brooke ileostomy 1501
Restorative proctocolectomy with ileal pouch–anal anastomosis 1501
Controversies in ileal reservoir surgery 1504
Proctocolectomy with continent ileostomy 1507
Total abdominal colectomy with Brooke ileostomy 1508
Colectomy with ileorectal anastomosis 1508
Laparoscopic surgery in Crohn’s disease and ulcerative colitis 1509
Crohn’s disease 1509
Crohn’s colitis 1510
Ulcerative colitis 1510
Indeterminate colitis 1511
Further reading 1511
CHAPTER 74: Microscopic colitis and other miscellaneous inflammatory and structural disorders of the colon 1513
Microscopic colitis 1513
Definition 1513
Epidemiology 1514
Risk factors 1515
Pathogenesis 1516
Clinical presentation and natural history 1517
Differential diagnosis 1517
Therapy and management 1518
Complications 1519
Geographic variation 1519
Other miscellaneous inflammatory and structural disorders of the colon 1519
Eosinophilic colitis 1519
Mast cell colitis 1520
Segmental colitis associated with diverticulosis 1521
Diversion colitis 1522
Solitary rectal ulcer syndrome 1523
Stercoral ulceration 1524
Medication-induced colonic injury 1525
Endometriosis 1525
Typhlitis 1526
Pneumatosis intestinalis 1526
Further reading 1528
E Colon 1529
CHAPTER 75: Irritable bowel syndrome 1529
Definition 1529
Epidemiology 1529
Prevalence 1529
Demographic factors: gender, age, socioeconomic status 1530
Geographic variation 1530
Morbidity and costs of irritable bowel syndrome 1531
Healthcare utilization 1531
Comorbidities 1531
Family history 1532
Prior gastrointestinal infection 1532
Stressful life events 1532
Pathogenesis 1533
Visceral sensation 1533
Enhanced visceral perception 1533
Mood and cognition: important mediators of altered visceral perception 1534
Central sensitization 1534
Endogenous pain modulation 1534
Peripheral contributions to visceral hypersensitivity 1534
Enhanced perception to somatic stimuli 1535
Changes in the stress response system 1535
Early adverse life events 1535
The hypothalamic–pituitary–adrenal axis 1536
The autonomic nervous system 1536
Transit and motility 1536
Serotonin 1537
Altered immune reactivity 1537
Increased gut permeability 1538
Gut microbiota 1538
Postinfectious irritable bowel syndrome 1538
Genetics 1539
Bile acid processing 1539
Clinical presentation and natural history 1539
Gastrointestinal symptoms 1539
Extraintestinal symptoms 1540
Gender 1540
Severity 1540
Diagnostic approach and differential diagnosis 1541
Symptom-based criteria 1541
Alarm features 1542
Diagnostic testing 1542
Therapy and management 1544
Introduction 1544
Patient-centered care 1544
Diet 1545
Physical activity 1546
Pharmacological therapies 1546
Therapies for irritable bowel syndrome with constipation 1546
Therapies for irritable bowel syndrome with diarrhea 1549
Therapies for multiple subtypes of irritable bowel syndrome 1550
Nonpharmacological therapies 1552
Emerging therapies 1553
Complementary and alternative medicine approaches 1554
Prevention 1554
Temporal/secular trends 1554
Further reading 1555
CHAPTER 76: Diverticular disease of the colon 1556
Definitions 1556
Epidemiology (risk factors) 1556
Colonic diverticulosis 1556
Diverticular disease 1557
Acute diverticulitis 1559
Complicated diverticular disease 1559
Pathogenesis 1560
Changes in connective tissue 1560
Colonic motility 1560
Alteration in enteric nerves 1560
Genetic factors 1561
Clinical presentation and natural history 1561
Diverticulosis 1561
Diverticular disease 1561
Acute diverticulitis 1561
Complicated diverticular disease 1562
Differential diagnosis 1563
Therapy and management 1563
Diverticulosis 1563
Diverticular disease 1563
Acute diverticulitis 1565
Complicated diverticular disease 1566
Complications 1568
Prevention 1568
Acute diverticulitis 1568
Complicated diverticular disease 1568
Temporal/secular trends 1569
Diverticulosis 1569
Diverticular disease 1569
Acute diverticulitis 1569
Complicated diverticular disease 1569
Geographic variation 1570
Further reading 1570
CHAPTER 77: Polyps of the colon and rectum 1573
Introduction 1573
Mucosal polyps 1573
Adenomatous polyps 1573
Serrated polyps 1583
Hamartomatous polyps 1586
Miscellaneous polyps 1587
Submucosal polyps 1587
Lipomas 1588
Colitis cystica profunda 1588
Pneumatosis cystoides coli 1588
Carcinoid tumors 1588
Further reading 1589
CHAPTER 78: Malignant tumors of the colon 1590
Epidemiology 1590
Temporal trends 1591
Geographic variation 1591
Dietary patterns 1591
Lifestyle factors 1594
Clinical conditions predisposing to colorectal cancer 1595
Pathogenesis of colorectal cancer 1600
Molecular pathways that lead to colorectal cancer 1600
Inflammation and colorectal cancer development 1604
Microbiome 1604
Clinical manifestations and natural history 1604
Clinical symptoms and signs associated with colorectal cancer 1604
Gross pathology 1606
Microscopic pathology 1606
Natural history of colorectal cancer 1606
Prognostic features associated with colorectal cancer 1607
Predictive factors associated with colorectal cancer 1609
Differential diagnosis 1609
Colorectal lymphoma 1610
Colorectal neuroendocrine tumors 1611
Kaposi sarcoma 1611
Mesenchymal tumors of the colorectum 1611
Metastatic disease to the colorectum 1611
Treatment for colorectal cancer 1612
Surgical treatment for localized colon cancer 1612
Surgical treatment for localized rectal cancer 1612
Surgical complications 1612
Adjuvant therapy for nonmetastatic colon cancer 1613
Adjuvant therapy for rectal cancer 1613
Treatment for metastatic colorectal cancer 1614
Biological therapies for metastatic colorectal cancer 1614
Diet, lifestyle, and colorectal cancer survival 1615
Chemoprevention 1615
Aspirin/nonsteroidal antiinflammatory drugs 1615
Statins 1617
Other medications 1617
Acknowledgment 1617
Further reading 1617
CHAPTER 79: Polyposis syndromes 1619
Familial adenomatous polyposis 1619
Definition 1619
Epidemiology 1619
Genetics 1620
Clinical manifestations 1621
Syndromes related to familial adenomatous polyposis 1625
Differential diagnosis 1625
Clinical course and complications 1626
Management 1626
MUTYH-associated polyposis 1629
Definition 1629
Epidemiology 1629
Genetics 1629
Clinical presentation and natural history 1630
Differential diagnosis 1630
Surveillance and management 1631
Serrated polyposis syndrome (hyperplastic polyposis syndrome) 1631
Definition 1631
Epidemiology 1631
Genetics 1631
Clinical presentation and natural history 1631
Surveillance and management 1632
Peutz–Jeghers syndrome 1632
Definition, epidemiology, and clinical characteristics 1632
Genetics and pathophysiology 1634
Diagnosis, surveillance, and treatment 1634
Differential diagnosis 1634
Juvenile polyposis syndrome 1634
Definition, epidemiology, and clinical characteristics 1634
Genetics and pathophysiology 1635
Diagnosis, screening, and treatment 1635
PTEN hamartoma tumor syndrome 1636
Definition, epidemiology, and clinical characteristics 1636
Related syndromes 1637
Genetics 1637
Surveillance and management 1637
Polyposis syndromes with neural polyp histology 1637
Neurofibromatosis type 1 1637
Multiple endocrine neoplasia type 2B 1638
Isolated intestinal neurofibromatosis 1639
Polyposis syndromes with inflammatory polyps 1639
Inflammatory bowel disease 1639
Mucosal prolapse syndrome 1639
Polyposis conditions arising from lymphoid tissue 1639
Nodular lymphoid hyperplasia 1639
Multiple lymphomatous polyposis 1640
Immunoproliferative small intestinal disease 1640
Miscellaneous rare polyposis syndromes and conditions 1641
Constitutional mismatch repair deficiency syndrome 1641
Hereditary mixed polyposis syndrome 1641
Cronkhite–Canada syndrome 1641
Gorlin syndrome 1642
McCune–Albright syndrome 1642
Other reported rare polyposis conditions 1642
Further reading 1642
CHAPTER 80: Colorectal cancer screening 1644
Introduction 1644
Screening and surveillance 1644
Opportunistic screening versus population screening programs 1645
Screening tests and their impact on colorectal cancer incidence and mortality 1645
Guaiac-based fecal occult blood tests 1646
Fecal immunochemical tests 1649
Flexible sigmoidoscopy 1652
Flexible sigmoidoscopy combined with fecal testing 1652
Colonoscopy: effectiveness 1652
Colonoscopy: neoplasia after baseline exam, screening, and surveillance intervals 1655
Colonoscopy: quality, adenoma detection rate, interval cancer 1659
Flexible sigmoidoscopy and colonoscopy: complications in screening trials and community practice 1659
Other tests: fecal DNA testing, barium enema, computed tomography colonography, capsule endoscopy, blood-based biomarkers 1659
Effectiveness = participation × efficacy 1660
Population-level data in the context of screening trends 1661
Colorectal cancer screening and surveillance guidelines 1661
Decision analytic modeling 1661
The future 1662
Future considerations 1663
Glossary 1663
Acknowledgments 1664
Further reading 1664
CHAPTER 81: Anorectal diseases 1665
Anorectal examination 1665
Hemorrhoids 1666
Anatomy and epidemiology 1666
Pathogenesis 1666
Definitions 1666
Diagnosis and treatment 1666
Anorectal varices 1669
Anorectal abscess and fistula 1669
Etiology and differential diagnosis 1669
Classification 1669
Clinical manifestations 1670
Diagnostic tests 1671
Treatment 1671
Rectal prolapse 1672
Mucosal prolapse – hemorrhoids 1672
Procidentia 1673
Anal fissure 1674
Pathophysiology 1674
Clinical manifestations 1674
Treatment 1674
Anal stenosis 1675
Solitary rectal ulcer syndrome 1676
Pathogenesis 1676
Treatment 1676
Fecal incontinence 1676
Introduction 1676
Physiology of continence and defecation 1677
Pathophysiology of fecal incontinence 1677
Etiology of fecal incontinence 1678
Clinical evaluation 1678
Diagnostic testing 1679
Recommendations 1680
Management 1681
Pruritus ani 1682
Pathogenesis 1682
Treatment 1683
Proctalgia syndromes 1684
Chronic proctalgia 1684
Proctalgia fugax 1684
Coccygodynia 1685
Treatment 1685
Rectal foreign bodies and trauma 1685
Anal intraepithelial neoplasia 1686
Etiology 1686
Clinical features, diagnosis, and management 1686
Anal carcinoma 1686
Clinical manifestations 1687
Treatment 1687
Nonepidermoid anal malignancies 1687
Miscellaneous conditions 1687
Pilonidal disease 1687
Hidradenitis suppurativa 1688
Further reading 1688
F Pancreas 1689
CHAPTER 82: Acute pancreatitis 1689
History and definition 1689
Pathological definitions 1689
Clinical definitions 1690
Epidemiology (risk factors) 1691
Biliary pancreatitis 1691
Alcoholic pancreatitis and other toxins 1693
Pancreas divisum 1693
Sphincter of Oddi dysfunction 1693
Endoscopic retrograde cholangiography 1694
Drug-induced acute pancreatitis 1694
Hyperparathyroidism/hypercalcemia 1694
Hyperlipidemia/hypertriglyceridemia 1694
Autoimmune pancreatitis 1694
Tumors 1695
Duodenal disorders 1696
Infections 1696
Genetic 1696
Idiopathic 1697
Trauma 1697
Pancreatic biopsy 1697
Pancreatic ischemia 1697
Penetrating peptic ulcer disease 1697
Postoperative 1697
Coronary artery bypass and vascular diseases 1697
Pathogenesis (genetics) 1697
Autodigestion 1698
Inflammation 1699
Mitochondrial dysfunction 1700
Autophagy 1701
Obstruction 1701
Alcohol and its metabolites 1702
Geographic variation 1702
Rare complications of acute pancreatitis 1703
Diagnosis and differential diagnosis 1703
Atlanta classification [9] 1703
Symptoms 1703
Laboratory parameters 1703
Imaging 1704
Prediction of severity 1707
Difficulties in determining the prognosis of acute pancreatitis 1707
Parameters and scores used to assess prognosis in acute pancreatitis 1708
Therapy and management 1711
Blood counts/hematocrit 1711
Diagnostic and therapeutic approaches to resuscitation 1712
Nutrition 1714
Pain management 1715
Therapeutic approaches without high-grade evidence of efficacy 1715
Antibiotic prophylaxis and therapy 1716
Endoscopic retrograde cholangiography in biliary pancreatitis 1716
Invasive treatment of necrotizing pancreatitis (ANC and WON) 1717
Invasive treatment of interstitial edematous pancreatitis (APFC and pseudocyst) 1719
Therapy of autoimmune pancreatitis 1724
Prevention 1725
Primary prevention 1725
Secondary prevention 1726
Further reading 1727
CHAPTER 83: Autoimmune pancreatitis 1728
Introduction 1728
Type 1 autoimmune pancreatitis 1728
Historical perspective 1728
Definition 1728
Epidemiology 1729
Pathogenesis 1729
Clinical presentation 1729
Differential diagnosis 1731
Natural history 1732
Therapy and management 1733
Complications 1734
Prevention 1735
Geographic variation 1735
Type 2 autoimmune pancreatitis 1736
Historical perspective and definition 1736
Epidemiology 1736
Pathogenesis 1736
Clinical presentation 1736
Therapy and management 1736
Geographic variation 1736
Summary 1737
Further reading 1737
CHAPTER 84: Chronic pancreatitis 1738
Introduction 1738
Definition 1738
Epidemiology 1739
Etiology and risk factors 1739
Pathogenesis 1741
Clinical presentation and natural history including prognosis 1741
Acute relapse 1741
Pain syndrome 1741
Complications 1742
Diagnosis 1743
Laboratory tests 1743
Diagnosis of exocrine pancreatic insufficiency 1743
Diagnostic imaging 1745
Differential diagnosis 1749
Therapy and management of complications 1749
Intensive care 1749
Treatment of pain 1750
Nutrition in acute pancreatitis or in acute relapses of chronic pancreatitis 1750
Antibiotics 1751
Treatment of necrosis (see Chapter 82) 1751
Further indications for interventional endoscopic or surgical therapy 1752
Pain management 1758
Therapy of exocrine pancreatic insufficiency 1760
Therapy of endocrine insufficiency 1762
Nutrition for patients with chronic pancreatitis 1762
Surgical procedures and their indications 1763
Treatment of postoperative complications 1765
Prevention and follow-up 1765
Follow-up after surgical management 1765
Monitoring and follow-up of chronic pancreatitis 1765
Acknowledgment 1766
Further reading 1766
CHAPTER 85: Hereditary diseases of the pancreas 1768
Introduction 1768
Definitions 1769
Pancreatic structure, function, and molecular pathogenesis (see Chapters 12, 25, and 83) 1770
The pancreas 1770
Specific genetic disorders of the pancreas 1771
Hereditary pancreatitis 1771
CF and CFTR-related pancreatitis 1776
Overview 1776
SPINK1-associated familial pancreatitis 1779
Overview 1779
Shwachman-Diamond syndrome 1780
Overview 1780
Johanson-Blizzard syndrome 1781
Other genetic factors 1781
Pancreatitis with complex genotypes 1781
Other pancreatitis susceptibility and modifier genes 1782
Pancreatitis risk gene associated with alcohol – CLDN2 locus 1782
CPA1-associated pancreatitis 1782
Further reading 1783
CHAPTER 86: Cystic lesions of the pancreas 1784
Introduction 1784
Mucinous cystic neoplasm 1784
Serous cystadenoma 1786
Solid pseudopapillary neoplasm 1786
Cystic pancreatic endocrine neoplasm 1787
Intraductal papillary mucinous neoplasm 1787
MD-IPMN 1789
BD-IPMN 1790
Other rare cystic neoplasms 1793
Role of imaging, EUS, and cyst fluid analysis in the differential diagnosis and treatment of CNP 1793
EUS imaging 1793
EUS and pancreatic cyst fluid analysis 1794
Therapeutic EUS 1795
Which patients with CNP benefit from EUS? 1795
Surgical treatment 1796
Postoperative surveillance 1796
Further reading 1796
CHAPTER 87: Adenocarcinoma of the pancreas 1797
Epidemiology 1797
Risk factors 1798
Obesity 1798
Age 1798
Gender 1798
Race 1798
Cigarette smoking 1798
Diabetes mellitus 1798
Alcohol 1799
Chronic pancreatitis 1799
Diet 1799
Hereditary factors 1800
Pathology 1800
Pathogenesis 1801
Commonly mutated genes in pancreatic cancer 1802
Embryonic signaling pathways 1803
Tumor microenvironment 1803
Pancreatic cancer stem cells 1804
Clinical presentation and natural history 1804
Differential diagnosis and staging 1804
Diagnostic laparoscopy 1806
Therapy and management 1807
Preoperative biliary drainage 1807
Metallic versus plastic biliary stents 1808
Surgical resection 1808
Adjuvant therapy 1809
Neoadjuvant therapy 1811
Borderline resectable pancreatic cancer 1811
Locally advanced pancreatic adenocarcinoma 1812
Metastatic pancreatic adenocarcinoma 1813
Biomarker correlatives and future trial design 1815
Complications 1815
Prevention 1816
Secular trends 1816
Geographical variation 1816
Further reading 1817
CHAPTER 88: Neuroendocrine tumors of the pancreas 1818
Introduction 1818
Epidemiology 1818
Pathogenesis 1820
Classification and pathology 1822
Classification 1822
Pathology 1824
Clinical presentation and natural history 1825
Nonfunctional pancreatic neuroendocrine tumors 1825
Insulinoma 1826
VIPoma 1826
Glucagonoma 1827
Somatostatinoma 1827
Enterochromaffin cell tumor 1828
Miscellaneous pancreatic neuroendocrine tumors 1829
Poorly differentiated pancreatic endocrine carcinoma 1829
MEN1 syndrome 1829
Other genetic syndromes 1830
Differential diagnosis 1830
Nonfunctional pancreatic neuroendocrine tumors 1830
Functional syndromes 1831
MEN1-associated pancreatic neuroendocrine tumors 1832
Tumor localization 1832
Therapy and management 1837
Surgical treatment 1837
Medical therapy 1839
Ablative therapies for metastatic pancreatic neuroendocrine tumors 1841
Cytotoxic therapy of metastatic gastroenteropancreatic neuroendocrine tumors 1841
Biological and targeted therapies 1842
Further readings 1842
G Gallbladder and biliary tract 1844
CHAPTER 89: Gallstones 1844
Definition 1844
Epidemiology 1844
Risk factors 1846
Pathophysiology 1846
Chemical species of lipids in bile 1846
Physical states of biliary lipids 1846
Major sources of cholesterol for biliary secretion 1848
Hepatic secretion of biliary lipids 1849
Pathogenesis of the formation of cholesterol gallstones 1849
Pathogenesis of the formation of pigment gallstones 1852
Genetic analysis of gallstone disease 1855
Natural history, clinical presentation, and diagnosis 1856
Natural history 1856
Symptomatic gallstone disease 1856
Diagnosis of gallstones 1857
Differential diagnosis 1857
Therapy and management 1857
Asymptomatic cholelithiasis 1857
Therapy of the biliary colic 1857
Cholecystectomy 1859
Prophylactic cholecystectomy 1861
Oral litholysis with bile acids 1861
Special therapeutic decisions: gallstones in pregnancy 1862
Complications 1862
Acute cholecystitis 1862
Gallstone ileus 1863
Chronic cholecystitis 1863
Choledocholithiasis 1864
Cholestatic jaundice 1865
Acute cholangitis 1865
Acute biliary pancreatitis 1865
Cholesterolosis and gallbladder polyps 1866
Gallbladder carcinoma and porcelain gallbladder 1866
Recurrent pyogenic cholangitis 1867
Acalculous cholecystitis 1867
Prevention and protective factors 1867
Primary prevention 1867
Prevention of biliary colic 1868
Prevention of gallstone recurrence 1868
Grading of strength of recommendations and quality of evidences 1868
Further reading 1870
CHAPTER 90: Primary sclerosing cholangitis 1871
Epidemiology 1871
Pathogenesis 1872
Genetic factors 1872
Immune-mediated alterations 1873
Environmental factors 1873
Clinical manifestations 1873
Asymptomatic primary sclerosing cholangitis 1873
Symptomatic primary sclerosing cholangitis 1874
Differential diagnosis (Box 90.1) 1876
Disease-related complications 1877
Fatigue 1877
Pruritus 1877
Metabolic bone disease 1877
Steatorrhea 1877
Micronutrient deficiency 1878
Biliary calculi 1878
Dominant stricture 1878
Bacterial cholangitis 1878
Cholangiocarcinoma 1878
Colonic dysplasia/carcinoma 1879
Pregnancy 1879
Disease-modifying therapies 1879
Endoscopic therapy 1880
Liver transplantation 1880
Natural history and prognosis 1881
Variant primary sclerosing cholangitis syndromes 1882
Small duct primary sclerosing cholangitis 1882
Autoimmune hepatitis 1882
Idiopathic adulthood ductopenia 1883
Summary 1883
Further reading 1883
CHAPTER 91: Cystic diseases of the liver and biliary tract 1884
Cystic diseases of the biliary tract 1884
Epidemiology 1884
Classification 1884
Pathogenesis 1885
Clinical presentations 1886
Diagnosis 1887
Pathology 1888
Treatment 1888
Clinical course and complications 1890
Polycystic liver disease 1890
Epidemiology 1890
Pathogenesis 1890
Clinical presentation 1891
Diagnosis 1891
Treatment 1892
Further reading 1893
CHAPTER 92: Tumors of the biliary tract 1894
Benign tumors 1894
Benign tumors of the biliary tract 1894
Benign tumors of the gallbladder 1895
Overview of biliary tract cancers 1895
Definition 1895
Risk factors 1896
Pathogenesis 1897
Complications 1897
Prevention 1898
Temporal/secular trends 1898
Geographic variations 1898
Intrahepatic cholangiocarcinoma 1898
Definition 1898
Clinical presentation and natural history 1898
Differential diagnosis 1898
Therapy and management 1899
Perihilar cholangiocarcinoma 1900
Definition 1900
Clinical presentation and natural history 1900
Differential diagnosis 1900
Therapy and management 1901
Distal cholangiocarcinoma 1904
Definition 1904
Clinical presentation and natural history 1904
Differential diagnosis 1904
Therapy and management 1905
Gallbladder cancer 1906
Definition 1906
Epidemiology (risk factors) 1906
Pathogenesis 1907
Clinical presentation and natural history 1907
Differential diagnosis 1908
Therapy and management 1908
Complications 1909
Prevention 1909
Temporal/secular trends 1909
Geographic variation 1909
Further reading 1909
CHAPTER 93: Sphincter of Oddi dysfunction and postcholecystectomy syndrome 1911
Introduction 1911
Definitions 1911
Anatomy 1911
Physiology 1912
Diagnosis and classification 1912
Milwaukee Biliary Group classification 1912
Rome III criteria 1913
Clinical presentation and demographics 1913
Diagnosis via noninvasive imaging 1913
Morphine–prostigmin provocation test (Nardi test) 1914
Secretory imaging studies 1914
Hepatobiliary scintigraphy 1914
Diagnosis via ERCP with SOM 1914
Technique 1914
Therapy 1917
Pharmacological therapy 1917
Acupuncture 1917
Surgery 1917
Endoscopy 1917
Recurrent pancreatitis 1918
Chronic pancreatitis 1919
Stenting, balloon dilatation, and botulinum toxin injection 1919
Complications 1920
Approaches to treatment failure 1920
Controversies 1920
Conclusion 1921
Further reading 1921
H Liver 1922
CHAPTER 94: Acute viral hepatitis 1922
Introduction 1922
Epidemiology 1922
Overview 1922
Hepatitis A virus 1923
Hepatitis B virus 1923
Hepatitis C virus 1924
Hepatitis D virus 1925
Hepatitis E virus 1925
Virology 1926
Hepatitis A virus 1926
Hepatitis B virus 1927
Hepatitis C virus 1929
Hepatitis D virus 1930
Hepatitis E virus 1931
Pathogenesis 1931
Primary infection 1932
Immune responses 1932
Clinical manifestations 1934
Extrahepatic manifestations 1935
Diagnosis and differential diagnosis 1936
Serology 1936
Laboratory features 1938
Histology 1939
Differential diagnosis 1939
Clinical course and complications 1941
Clinical course 1941
Complications 1941
Prevention and immunoprophylaxis 1942
Hepatitis A virus 1942
Hepatitis B virus 1943
Hepatitis C virus 1945
Hepatitis D virus 1945
Hepatitis E virus 1945
Pre- and postexposure prophylaxis 1945
Treatment 1947
General recommendations 1947
Specific therapy 1947
Other viruses 1949
Herpes simplex virus types 1 and 2 1949
Epstein–Barr virus 1949
Cytomegalovirus 1950
Recently discovered viruses 1950
Further reading 1951
CHAPTER 95: Chronic hepatitis B viral infection 1952
Introduction 1952
Clinical presentations and disease phases 1953
Phases of disease after neonatal acquisition of HBV infection 1955
Serological and molecular diagnosis 1956
Epidemiology 1957
Prevalence 1957
Transmission 1957
Coinfection: risk groups 1958
Prevention 1958
Hepatitis B virus variants and mutants 1959
Mutants affecting HBeAg production 1959
X gene mutants 1959
Pre-S/S gene mutants 1960
Polymerase gene mutations 1960
Genotypes and serotypes 1961
Clinical manifestations and laboratory tests 1961
Differential diagnosis 1962
Course and complications 1963
Coinfection 1963
HBV coinfection with hepatitis D (“delta”) virus 1963
HBV coinfection with HIV 1964
HBV coinfection with HCV 1965
HBV coinfection with hepatitis A virus 1965
Treatment 1965
Definitions of response to treatment 1965
Antiviral drug resistance testing 1967
Therapeutic agents 1967
Chronic hepatitis B treatment in practice 1970
Genotypic resistance of hepatitis B virus to nucleoside analogues 1972
Lamivudine resistance 1972
Adefovir and tenofovir resistance 1972
Entecavir resistance 1973
Telbivudine resistance 1973
Management of special populations 1973
Further reading 1974
CHAPTER 96: Hepatitis C virus infection 1975
Definition 1975
Epidemiology (risk factors) 1975
Incidence 1975
Prevalence 1976
Demographic characteristics 1976
Modes of transmission 1976
Pathogenesis (genetics) 1978
Molecular virology of hepatitis C virus 1978
Genotypes and quasispecies 1978
Pathophysiology and host immune response 1979
Histopathology 1980
Clinical presentation and natural history 1980
Diagnosis of HCV infection 1980
Screening for HCV infection 1981
Acute HCV infection 1982
Spontaneous resolution versus chronicity 1982
Chronic HCV infection 1982
Progression to HCV-related cirrhosis 1983
Differential diagnosis 1983
Therapy and management 1983
Aims of antiviral therapy 1984
Historical perspectives on treatment for chronic HCV infection 1984
Predictors of treatment response 1984
Genotype 1 infection 1985
Treatment of chronic HCV other than genotype 1 1986
Side-effects of HCV treatment 1986
Selection of patients for HCV treatment 1988
Selected populations 1988
Investigational therapies 1990
Complications 1991
HCV and hepatocellular carcinoma 1991
Extrahepatic manifestations of HCV infection 1991
Prevention 1993
Prevention of HCV transmission 1993
HCV vaccine development 1993
Further reading 1993
CHAPTER 97: Drug-induced liver disease 1994
Epidemiology 1994
Drug metabolism and mechanisms of hepatotoxicity 1994
Enzyme polymorphism 1995
Other mechanisms 1997
Classification of hepatotoxic agents 1997
Intrinsic (dose-dependent) agents 1997
Idiosyncratic reactions 1998
Types of drug reactions, clinical presentations 1999
Hepatocellular reactions 1999
Cholestatic reactions 2002
Immunoallergic reactions 2002
Steatohepatitis 2003
Other drug reactions 2003
Treatment 2003
Criteria for causal assessment of drug-induced liver injury 2003
Lessons from drugs withdrawn from the market 2004
The drug approval process 2005
Research and development 2005
Clinical trials 2005
Postmarketing surveillance 2006
Hepatotoxicity in the patient with chronic liver disease 2006
Clinician’s guide to handling new drugs 2007
Further reading 2007
CHAPTER 98: Acute liver failure 2009
Introduction 2009
Definition and history 2009
Recognition of the condition 2010
Epidemiology 2010
Etiology 2011
Acetaminophen-related liver injury 2011
Idiosyncratic drug reactions 2015
Viral hepatitis 2015
Other causes of acute liver failure 2016
Pathogenesis 2018
Clinical management 2019
Overall considerations on admission 2020
Hepatic encephalopathy and cerebral edema 2020
Infection in acute liver failure 2021
Bleeding in acute liver failure and management of coagulation 2021
Managing fluids and kidney injury 2021
Therapy of acute liver failure 2021
N-acetylcysteine for nonacetaminophen acute liver failure 2021
Prognosis and the role of transplantation 2022
Prognostic scores 2023
Long-term follow-up 2023
Specific therapies undergoing trial 2023
Bioartificial liver assist devices 2023
Summary 2024
Further reading 2024
CHAPTER 99: Autoimmune hepatitis 2025
Pathogenesis 2025
Clinical presentation 2026
Diagnosis 2027
Physical examination 2027
Laboratory abnormalities 2028
Liver histology 2028
Differential diagnosis 2029
Treatment 2031
Salvage therapies 2034
Liver transplantation 2034
Long-term prognosis 2034
Overlap with other autoimmune liver diseases (see Chapters 90 and 100) 2035
Summary 2035
Further reading 2035
CHAPTER 100: Primary biliary cirrhosis 2036
Introduction 2036
Pathogenesis 2036
Antimitochondrial antibodies 2036
Environmental risk factors 2038
Genetics 2038
Immune-mediated destruction of biliary epithelial cells 2038
Clinical manifestations 2039
Clinical presentation 2039
Signs/symptoms 2039
Serological findings 2039
Histology 2040
Epidemiology 2041
Extrahepatic conditions reported to be associated with primary biliary cirrhosis 2042
Differential diagnosis 2043
Course and complications 2044
Clinical course 2044
Complications 2044
Treatment 2045
Therapy of primary biliary cirrhosis 2045
Management of complications 2047
Treatment of variant forms of primary biliary cirrhosis 2048
Further reading 2049
CHAPTER 101: Hemochromatosis 2050
Definition 2050
Epidemiology 2050
Pathogenesis 2050
Clinical presentation and natural history 2051
Differential diagnosis 2052
Diagnostic tests 2052
Diagnosis of non-HFE hemochromatosis and secondary iron overload 2054
Genetic testing for non-HFE hemochromatosis and secondary iron overload 2055
Therapy and management 2056
Liver transplantation 2056
Complications 2056
Liver disease 2056
Hepatocellular carcinoma 2057
Diabetes 2057
Cardiac disease 2057
Arthropathy 2057
Endocrine abnormalities 2057
Pigmentation of the skin 2057
Fatigue 2057
Prevention 2057
Population screening 2057
Family studies 2058
Temporal/secular trends 2058
Geographical variation 2058
Further reading 2058
CHAPTER 102: Metabolic diseases of the liver 2059
Wilson disease 2060
Clinical features 2060
Genetics 2062
Pathogenesis and biochemistry 2062
Diagnosis 2063
Treatment 2064
Reye syndrome 2065
Clinical features 2065
Histology 2065
Genetics 2066
Pathogenesis and biochemistry 2066
Diagnosis 2066
Treatment 2066
Alpha-1 antitrypsin deficiency 2066
Clinical features 2067
Hepatic histology 2067
Genetics 2067
Pathogenesis and biochemistry 2068
Diagnosis 2068
Treatment 2068
Porphyria 2069
Acute porphyrias 2069
Acute intermittent porphyria 2070
Other acute porphyrias 2070
Cutaneous porphyrias 2070
Porphyria cutanea tarda 2070
Erythropoietic protoporphyria 2071
Congenital erythropoietic porphyria 2071
Metabolic diseases of the neonate and childhood 2071
Hereditary tyrosinemia 2071
Galactosemia 2072
Hereditary fructose intolerance 2073
Glycogen storage diseases 2073
Mitochondrial hepatopathies 2076
Further reading 2078
CHAPTER 103: Alcoholic liver disease 2079
Introduction 2079
Burden of alcoholic liver disease 2080
Natural history and modifying factors 2081
Pathogenesis 2082
Diagnosis 2083
Alcohol abuse as a cofactor of other liver diseases 2085
Alcoholic cirrhosis and hepatocellular carcinoma 2086
Alcoholic hepatitis (AH) 2087
Epidemiology 2087
Noninvasive markers 2087
Diagnosis 2087
Predict outcomes 2087
Treatment 2089
Liver transplantation for alcoholic liver disease 2089
Patient selection 2090
Medical evaluation 2090
Posttransplant care 2090
Further readings 2091
CHAPTER 104: Nonalcoholic fatty liver disease 2092
Introduction 2092
Definition 2092
Epidemiology 2092
Nonalcoholic fatty liver disease and metabolic syndrome 2093
Gender and ethnicity 2093
Age 2093
Familial and genetic factors 2093
Histopathology 2093
Pathogenesis 2095
Role of insulin resistance 2096
Energy homeostasis and hepatic steatosis 2097
Peroxisome proliferator-activated receptors 2097
Hepatic fat accumulation worsens insulin resistance 2098
Mediators of cellular injury in steatohepatitis 2098
Oxidative stress 2098
Hepatocyte apoptosis 2099
Intestinal microbiome 2099
Mechanism of fibrosis 2100
Clinical features of nonalcoholic fatty liver disease and associated diseases 2100
Signs or symptoms 2100
Cardiovascular disease 2100
Hepatocellular carcinoma 2100
Diagnostic approach 2101
Liver biopsy 2101
Noninvasive diagnosis 2101
Treatment 2101
Weight loss 2102
Insulin sensitizers 2102
Metformin 2102
Thiazolidinediones 2103
Vitamin E 2103
Other approaches 2104
Summary 2104
Further reading 2104
CHAPTER 105: Hepatic fibrosis and cirrhosis 2106
Introduction 2106
Pathogenesis of fibrosis and cirrhosis 2106
Overview 2106
The ECM in normal and fibrotic liver 2107
Cellular effectors of fibrosis 2108
Stellate cell activation phenotypes 2111
ECM-cell and cell-cell interactions 2112
Signaling in stellate cells 2113
Reversion of liver fibrosis (and the fate of activated stellate cells) 2113
Clinical aspects of hepatic fibrosis and cirrhosis 2113
Epidemiology and burden of disease 2113
Risk factors for progression of fibrosis 2114
Methods to measure fibrosis 2114
Natural history 2117
Prognosis 2117
Regression of fibrosis and cirrhosis 2118
Treatment of fibrosis 2119
Treatments targeting inflammation 2119
Treatments targeting oxidant stress 2120
Cytoprotective treatments 2120
Agents that inhibit fibrosis via specific effects on stellate cells 2120
Compounds that directly interfere with matrix synthesis 2121
Novel potential antifibrotics 2121
Summary and future directions for antifibrotic therapy 2122
Further reading 2122
CHAPTER 106: Ascites and its complications 2123
Introduction 2123
Approach to the patient with suspected ascites 2123
Imaging investigation 2124
Approach to the patient with new-onset ascites 2124
Initial evaluation 2124
Diagnostic paracentesis 2124
Appearance of ascitic fluid 2124
Serum ascites albumin gradient and ascites total protein levels 2125
Hepatic venous pressure gradient measurement 2126
Evaluation of infection 2127
Evaluation of malignancy 2127
Evaluation of peritoneal tuberculosis 2128
Evaluation of pancreatic ascites 2128
Evaluation of chylous ascites 2128
Approach to the cirrhotic patient with ascites 2129
Pathogenesis and natural history of cirrhotic ascites 2129
Therapies for ascites 2130
Approach to the patient with cirrhosis and uncomplicated ascites 2133
Approach to the cirrhotic patient with refractory ascites 2134
Approach to the patient with cirrhosis and hepatic hydrothorax 2136
Approach to the patient with spontaneous bacterial peritonitis 2136
Approach to the patient with cirrhosis and acute kidney injury 2138
Approach to the patient with hepatorenal syndrome 2139
Therapies for hepatorenal syndrome 2140
Approach to the patient with suspected hepatorenal syndrome 2141
Further reading 2142
CHAPTER 107: Central nervous system and pulmonary complications of end-stage liver disease 2143
Hepatic encephalopathy 2143
Definition 2143
Division according to the severity of hepatic encephalopathy 2143
Epidemiology and burden 2144
Pathophysiology 2145
Clinical presentation 2147
Diagnosis 2148
Therapy and management 2150
Pulmonary complications 2155
Hepatopulmonary syndrome 2155
Definition 2155
Epidemiology 2155
Pathophysiology 2156
Diagnosis 2157
Therapy 2159
Portopulmonary hypertension 2160
Definition 2160
Epidemiology 2161
Pathophysiology 2161
Natural history 2161
Clinical presentation 2161
Diagnosis 2162
Therapy 2163
Further reading 2164
CHAPTER 108: Liver transplantation 2165
Introduction 2165
Historical perspective 2165
Indications for liver transplantation 2166
Prognostic models and organ allocation 2166
The evaluation for transplant 2168
Absolute contraindications to liver transplantation 2169
Relative contraindications 2169
Wait list management and delisting 2170
Organ allocation 2171
Expanding the donor pool 2171
Disease-specific considerations 2172
Alcohol-related liver disease 2172
Hepatitis C 2172
Hepatitis B 2172
Cholestatic liver disease 2173
Hepatocellular carcinoma 2173
Cholangiocarcinoma 2173
Inherited/metabolic liver disease 2174
Autoimmune hepatitis 2174
Fulminant hepatic failure 2174
Liver transplant immunosuppression 2175
Posttransplant complications (Figure 108.7) 2175
Early complications 2175
Late complications after liver transplant 2178
Further reading 2181
CHAPTER 109: Hepatocellular carcinoma 2182
Definition 2182
Risk factors 2182
Hepatitis B 2182
Hepatitis C 2183
Metabolic syndrome and nonalcoholic steatohepatitis 2183
Alcohol abuse and alcoholic cirrhosis 2184
Cirrhosis due to other causes 2184
Demographic risk factors 2184
Tobacco 2185
Diet 2185
Temporal/secular trends 2185
Geographical variation 2185
Pathogenesis 2186
Receptor tyrosine kinase pathways 2186
Wnt/?-catenin pathway 2187
PI3 kinase/AKT/mTOR pathway 2187
Angiogenic pathways 2187
Telomerase 2187
Stem cells 2187
Clinical presentation and natural history 2188
Clinical presentation 2188
Natural history 2190
Staging 2191
Diagnosis 2192
Radiological diagnosis 2192
Histological diagnosis 2194
Treatment 2195
Hepatic resection 2195
Liver transplantation 2196
Local ablative therapies 2197
Transarterial chemoembolization 2197
Transarterial radioembolization 2198
Systemic therapy 2198
Multidisciplinary management 2199
Complications 2199
Prevention 2199
Hepatitis B virus infection 2200
Hepatitis C virus infection 2200
Statins 2200
Coffee 2201
Summary 2201
Further reading 2201
CHAPTER 110: Liver abscess 2202
Epidemiology 2202
Pathogenesis 2202
Amebic abscess 2202
Pyogenic abscess 2202
Clinical presentation and natural history 2203
Amebic abscess 2203
Pyogenic abscess 2203
Differential diagnosis 2203
Therapy and management 2205
Amebic abscess 2205
Pyogenic abscess 2206
Further reading 2206
CHAPTER 111: Vascular diseases of the liver 2207
Systemic circulatory disease 2207
Ischemic hepatitis 2207
Congestive hepatopathy 2207
Hypoxia 2208
Budd–Chiari syndrome 2208
Risk factors 2208
Clinical features 2208
Diagnosis 2209
Management of primary Budd–Chiari syndrome 2210
Portal vein thrombosis 2211
Risk factors 2211
Acute portal vein thrombosis 2211
Chronic portal vein thrombosis 2212
Portal vein thrombosis in cirrhosis 2213
Sinusoidal obstruction syndrome (hepatic venoocclusive disease) 2214
Pathogenesis 2214
Risk factors 2214
Clinical presentation 2214
Diagnosis 2214
Prevention 2215
Treatment 2215
Prognosis 2215
Adaptation to heterogenous perfusion 2216
Risk factors 2216
Clinical presentation 2217
Diagnosis 2217
Treatment 2217
Outcome 2217
Peliosis hepatis 2217
Risk factors 2217
Clinical presentation 2218
Further reading 2218
I Miscellaneous 2219
CHAPTER 112: Intraabdominal abcesses and fistulae 2219
Definition 2219
Epidemiology 2219
Intraabdominal abscesses 2219
Gastrointestinal fistulae 2220
Pathogenesis 2221
Intraabdominal abscesses 2221
Gastrointestinal fistulae 2221
Clinical presentation and natural history 2221
Intraabdominal abscesses 2221
Gastrointestinal fistulae 2222
Differential diagnosis 2222
Therapy and management 2222
Plain and contrast radiography 2222
Ultrasound 2223
Nuclear medicine 2224
Computed tomography 2224
Magnetic resonance imaging (MRI) 2224
Treatment of intraabdominal abscesses 2227
Treatment of abscesses in Crohn’s disease 2227
Treatment of appendiceal and diverticular abscesses 2227
Treatment of gastrointestinal fistulae 2228
Complications 2229
Prevention 2229
Temporal trends 2229
Geographic variation 2229
Further reading 2230
CHAPTER 113: Diseases of the peritoneum, retroperitoneum, mesentery, and omentum 2231
Peritoneum 2231
Embryology, anatomy, and physiology 2231
Peritonitis 2231
Retroperitoneum 2239
Retroperitoneal hemorrhage 2239
Retroperitoneal infections 2239
Retroperitoneal fibrosis 2240
Retroperitoneal neoplasms 2242
Mesentery and omentum 2243
Mesenteric panniculitis and retractile mesenteritis 2243
Mesenteric fibromatosis 2245
Cysts and tumors of the mesentery and omentum 2245
Further reading 2246
CHAPTER 114: Nutrition supplementation 2247
Introduction and pathophysiology 2247
Nutritional assessment 2248
Initiation of nutrition support 2249
Enteral versus parenteral nutrition 2249
Timing of initiation 2250
Total energy and protein goals 2250
Refeeding syndrome 2250
Types of enteral formulas 2250
Enteral access 2251
Endoscopic placement of nasoenteric tubes 2252
Percutaneous enteral access 2253
Percutaneous endoscopic gastrostomy 2253
Percutaneous direct gastrostomy tube 2254
Surgical gastrostomy 2254
Percutaneous gastrojejunostomy tube 2254
Direct percutaneous endoscopic jejunostomy 2254
Surgical jejunostomy 2255
Parenteral nutrition 2255
Intravenous access 2255
Writing the parenteral nutrition prescription 2255
Complications of parenteral nutrition 2256
Common indications for enteral and parenteral feeding in specific disease conditions 2258
Short bowel syndrome 2258
Acute pancreatitis 2262
Nutritional management of the outpatient 2262
Home enteral nutrition 2262
Monitoring 2263
Home parenteral nutrition 2263
Further reading 2265
CHAPTER 115: Obesity: treatment and complications 2266
Definition 2266
Epidemiology 2266
Pathogenesis 2267
Concept of energy homeostasis 2268
Gastrointestinal hormones and food intake 2268
Clinical presentation 2269
Complications 2270
Gastrointestinal complications 2271
Treatment of obesity 2272
Treatment guidelines 2272
Lifestyle modifications 2272
Pharmacotherapy 2273
Surgical therapy 2274
Endoscopic therapy 2276
Complications of weight loss 2276
Conclusion 2277
Further reading 2277
CHAPTER 116: Bariatric surgery 2278
Introduction 2278
Preoperative and perioperative concerns 2279
Results 2280
Evolution of bariatric surgery 2281
Types of surgery 2284
Laparoscopic adjustable gastric banding (Figure 116.3a) 2284
Sleeve gastrectomy (Figure 116.3b) 2285
Roux-en-Y gastric bypass (Figure 116.3c) 2285
Biliopancreatic diversion with duodenal switch (Figure 116.3d) 2286
Complications of bariatric surgery 2286
Adjustable gastric banding 2287
Sleeve gastrectomy 2288
Roux-en-Y gastric bypass 2290
Biliopancreatic diversion with duodenal switch 2291
Other complications 2292
Revisional bariatric surgery 2295
Types of revisions 2296
New innovations and investigational procedures 2297
Ileal transposition (ileal interposition) 2297
Duodenojejunal exclusion 2297
Greater curvature/gastric plication 2298
Natural orifice transluminal endoscopic surgery (see Chapter 143) 2298
Endoluminal surgery 2299
Gastric/vagal pacing 2299
Further reading 2300
CHAPTER 117: Eating disorders 2301
Introduction 2301
Epidemiology of anorexia nervosa and bulimia nervosa 2301
Recognizing eating disorders 2302
Anorexia nervosa 2302
Bulimia nervosa 2302
Could anorexia nervosa and bulimia nervosa share an underlying pathophysiology? 2302
Three cardinal features of eating disorder 2303
Distorted body image 2303
Alteration in processing of signals of hunger and satiety (see Chapters 12 and 14) 2303
Feelings of ineffectiveness and other psychological changes 2304
Natural history of eating disorders 2304
Biology of response to caloric restriction 2304
Energy expenditure 2304
Using the body’s stored calories during inadequate caloric intake 2304
Searching for calories in the face of starvation 2305
Hyperactivity 2305
Impulsivity and obsession 2305
Mechanisms explaining hyperactivity and anxiety in anorexia nervosa 2305
Role of low blood glucose 2305
Role of hypoleptinemia 2305
Role of adiponectin 2306
Role of elevated neuropeptide Y 2307
Role of reduced sensitivity to ghrelin 2307
Explanation for female predominance 2307
Medical complications of eating disorders 2307
Gastrointestinal complications 2308
Cardiovascular complications 2309
Endocrine complications 2309
Treatment of anorexia nervosa and bulimia nervosa 2310
Psychiatric approach: directing treatment to psychological change 2310
Biological approach: directing treatment to the response to starvation 2311
Binge eating disorders, pica, rumination disorder, and avoidant/restrictive eating disorder 2311
Binge eating disorder 2311
Pica 2312
Rumination disorder 2312
Avoidant/ restrictive eating disorder 2312
Summary 2312
Further reading 2313
CHAPTER 118: Complications of HIV/AIDS and other secondary immunodeficiencies 2314
Role of the gastrointestinal mucosa in HIV-1 pathogenesis 2314
Diarrheal diseases 2314
Diagnostic evaluation 2315
Approach to therapy 2316
Highly active antiretroviral therapy 2317
Bacterial infections 2320
Protozoan infections 2323
Viral infections 2324
Fungal infections 2326
Biliary disorders 2328
Pancreatitis 2328
Gastrointestinal bleeding 2328
Gastrointestinal neoplasms 2328
Anorectal disease 2329
Other secondary immunodeficiency states 2329
Hematopoietic stem-cell transplant recipients 2329
Solid organ transplant recipients 2330
Neutropenia 2331
Further reading 2332
CHAPTER 119: Immunological disorders: (a) Food allergy and hypersensitivity 2333
Introduction 2333
Definitions 2333
Prevalence 2333
Mechanisms 2335
Implicated foods 2335
Clinical features 2335
Investigation and diagnostic testing 2336
In vivo and in vitro testing 2336
Natural history 2337
Prevention 2337
Management 2337
Disease modification 2337
Summary 2338
Further reading 2338
CHAPTER 120: Immunological disorders: (b) immunodeficiencies and gastrointestinal complications of organ transplantation 2339
Introduction 2339
Immunodeficiency disorders 2339
Primary immunodeficiency disorders and the gastrointestinal tract 2342
Predominantly antibody deficiencies 2342
Combined immunodeficiencies (B- and T-cell defects) 2345
Phagocytic cell defects 2346
Immune regulation defects and autoinflammatory disorders 2347
Complement pathway defects 2349
Inflammatory bowel disease and primary immunodeficiency 2350
Gastrointestinal complications of organ transplantation 2350
Intestinal disease secondary to conditioning protocols 2353
Graft-versus-host disease 2353
Further reading 2357
CHAPTER 121: Parasitic diseases: protozoa 2358
Introduction 2358
Extracellular protozoan parasites 2358
Amebiasis: Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii 2358
Giardia lamblia 2364
Blastocystis hominis 2367
Dientamoeba fragilis 2367
Balantidium coli 2367
Intracellular protozoan parasites 2367
Cryptosporidium 2368
Cyclospora cayetanensis 2370
Isospora belli 2371
Further reading 2372
CHAPTER 122: Parasitic diseases: helminths 2373
Introduction 2373
Stool examination for parasites [8] 2374
Nematodes (roundworms) 2376
Enterobius vermicularis (pinworm) 2376
Trichuris trichiura (whipworm) (trichuriasis) 2378
Trichostrongylus species 2380
Capillaria philippinensis and Capillaria hepatica (capillariasis) 2380
Ascaris lumbricoides (ascariasis) 2380
Ancylostoma duodenale and Necator americanus (hookworm) 2383
Strongyloides stercoralis (strongyloidiasis) 2385
Trichinella species (trichinosis) 2388
Toxocara species (visceral larva migrans and ocular toxocariasis) 2390
Angiostrongylus costaricensis (abdominal angiostrongyliasis) 2390
Ancylostoma species of dogs and cats (cutaneous larva migrans) 2391
Ancylostoma caninum (dog hookworm) and eosinophilic enteritis 2391
Anisakis species and Pseudoterranova decipiens (anisakiasis) 2392
Eustrongylides species (eustrongylidosis) 2393
Trematodes (flukes) 2393
Schistosoma species (schistosomiasis) 2393
Liver flukes 2398
Clonorchis sinensis (Chinese liver fluke) and Opisthorchis species (clonorchiasis and opisthorchiasis) 2398
Fasciola species (fascioliasis) 2400
Dicrocoelium dendriticum (dicrocoeliasis) 2401
Intestinal flukes 2402
Echinostoma species 2402
Fasciolopsis buski (giant intestinal fluke) (fasciolopiasis) 2402
Heterophyes heterophyes and Metagonimus yokogawai 2402
Cestodes (tapeworms) 2403
Diphyllobothrium species (fish tapeworm) (diphyllobothriasis) 2403
Taenia species (beef and pork tapeworm) (taeniasis, cysticercosis) 2404
Hymenolepis nana (dwarf tapeworm) and H. diminuta (rat tapeworm) (hymenolepiasis) 2408
Echinococcus species (cystic hydatid disease) (cystic and alveolar echinococcosis) 2408
Immune-mediated diseases and their relationship to improved hygiene and deworming of the population 2412
Acknowledgment 2413
Further reading 2413
CHAPTER 123: Gastrointestinal and hepatic manifestations of specific genetic disorders 2414
Overview 2414
The genetic architecture of human disease 2414
Mendelian diseases 2414
Complex multigenic diseases 2415
Approaches to identifying genetic disease associations 2415
The nature of genetic variation 2415
Genome-wide association studies. 2415
Exome sequencing 2416
Genetics in specific gastrointestinal and hepatic diseases 2416
Barrett esophagus 2416
Eosinophilic esophagitis 2416
Susceptibility to Helicobacter pylori infection 2420
Peptic ulcer disease 2420
Congenital diarrheas (Table 123.2) 2420
Effects of cystic fibrosis mutations on gastrointestinal function 2422
Genetic disorders of carbohydrate digestion and absorption 2422
Disorders of the intestinal epithelium 2425
Selective IgA deficiency 2426
Overlap between immune-mediated diseases 2426
Population based variability in liver function tests 2427
Disorders of bile salt metabolism and transport (Table 123.4) 2428
Cholesterol gallstones 2429
Disorders of bilirubin conjugation and transport (Table 123.5) 2430
Biliary atresia 2431
Alagille syndrome 2431
Inborn errors of metabolism 2432
Polycystic liver disease 2432
Hirschsprung disease 2433
Pancreatic agenesis 2433
Diaphragmatic hernias 2433
Hereditary hemorrhagic telangiectasia 2433
Further reading 2434
CHAPTER 124: Gastrointentinal manifestations of systemic diseases 2435
Introduction 2435
Cardiovascular diseases 2435
Aortic stenosis 2435
Congestive heart failure 2435
Coronary artery disease 2436
Chromosomal abnormalities and other genetic disorders 2438
Abetalipoproteinemia 2438
Down syndrome 2438
Fabry disease 2438
Familial Mediterranean fever 2438
Gaucher disease 2438
Hepatic porphyrias 2438
Hereditary angioedema 2439
Niemann–Pick disease 2440
Tangier disease 2440
Turner syndrome 2440
von Hippel–Lindau disease 2440
Connective tissue diseases 2440
Scleroderma 2440
Rheumatoid arthritis 2441
Systemic lupus erythematosus 2442
Other connective tissue diseases 2443
Dermatological diseases (see Chapter 125) 2444
Neurofibromatosis 2444
Pemphigus 2444
Epidermolysis bullosa 2444
Hereditary hemorrhagic telangiectasia 2444
Stevens–Johnson syndrome and erythema multiforme 2445
Endocrinological disorders 2446
Acromegaly 2446
Hyperparathyroidism 2446
Hypoparathyroidism 2446
Hypothyroidism 2446
Hyperthyroidism 2446
Other thyroid diseases 2447
Cushing syndrome 2447
Addison disease 2447
Endometriosis 2447
Diabetes mellitus 2447
Granulomatous diseases 2452
Sarcoidosis 2453
Tuberculosis 2454
Hematologic disease 2455
Hemoglobinopathies 2455
Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 2456
Plummer–Vinson syndrome 2457
Systemic amyloidoses 2457
Neoplastic disorders 2458
Oncologic emergencies 2458
Neutropenic enterocolitis (typhlitis) 2458
GI tract obstruction 2459
Cancer cachexia 2459
Consequences of chemotherapy and radiotherapy 2459
Paraneoplastic syndromes 2460
Metastatic disease to the GI tract 2461
Hematological malignancies 2461
Nonhematological malignancies 2463
Neurological diseases 2464
Neurogenic abdominal pain 2464
Cerebrovascular accident (stroke) 2465
Multiple sclerosis 2465
Dementia 2465
Spinal cord disorders 2466
Parkinson disease 2466
Autonomic dysfunction 2467
Neuromuscular disorders (Table 124.5) 2467
Pulmonary diseases and GI manifestations in patients requiring intensive care 2468
Cystic fibrosis 2470
Alpha-1-antitrypsin deficiency 2471
Obstructive pulmonary diseases and chronic cough 2471
Vasculitides 2471
Behçet disease 2471
Churg–Strauss syndrome 2472
Wegener granulomatosis 2472
Polyarteritis nodosa 2472
Henoch–Schönlein purpura (IgA Vasculitis) 2473
Cryoglobulinemia 2473
Giant cell arteritis 2473
Mood disorders 2474
Heavy metal toxicity 2474
Arsenic poisoning 2474
Gold 2475
Lead poisoning 2475
Further reading 2475
CHAPTER 125: Skin lesions associated with gastrointestinal and liver diseases 2476
Introduction 2476
Inherited disorders 2476
Inherited disorders with an increased risk of GI malignancy 2476
Genodermatoses with GI manifestations 2477
Acquired disorders 2480
Paraneoplastic and related syndromes 2480
Cutaneous signs of inflammatory bowel disease (see Chapters 71 and 72) 2482
Immunologically mediated diseases with GI manifestations 2485
Cutaneous manifestations of liver disease 2489
Cutaneous manifestations of pancreatic disease 2491
Mucocutaneous manifestations of nutritional deficiencies 2492
Cutaneous complications arising during treatment of HCV infection 2492
Further reading 2494
CHAPTER 126: Oral manifestation of gastrointestinal diseases 2495
Common oral manifestations of gastrointestinal and systemic diseases 2495
Altered taste 2495
Burning mouth 2495
Recurrent aphthous stomatitis 2495
Glossitis 2496
Angular cheilitis 2496
Oral pigmentation 2497
Vascular lesions / bleeding syndromes 2497
Gastrointestinal disorders and oral manifestations 2497
Gastroesophageal reflux disease 2497
Inflammatory bowel disease 2498
Celiac disease 2498
Graft-versus-host disease 2499
Behçet’s disease 2501
Hereditary hemorrhagic telangiectasia 2502
Blue rubber bleb nevus syndrome 2502
Gardner syndrome 2503
Puetz–Jeghers syndrome 2503
Cowden syndrome 2504
Miscellaneous 2504
Orofacial granulomatosis 2504
Drug-induced oral toxicity 2505
Further reading 2505
CHAPTER 127: Gastrointestinal vascular malformations and neoplasms: arterial, venous, arteriovenous, and capillary 2506
Introduction 2506
Dieulafoy lesion 2506
Pathology and pathophysiology 2507
Upper gastrointestinal lesions 2510
Mid and lower gastrointestinal lesions 2511
Gastric antral vascular ectasia 2511
Etiology 2511
Epidemiology and clinical manifestations 2512
Diagnosis 2512
Therapy 2512
Angiodysplasia 2513
Epidemiology and associated conditions 2513
Histology and pathogenesis 2514
Clinical manifestations 2514
Diagnosis 2516
Differential diagnosis 2517
Natural history 2517
Therapy 2517
Hereditary hemorrhagic telangiectasia 2519
Genetic defects 2519
Clinical manifestations 2519
Diagnosis 2520
Therapy 2520
Hemangiomas 2520
Capillary and cavernous hemangiomas 2520
Blue rubber bleb nevus syndrome 2522
Intestinal hemangiomas in Klippel–Trenaunay syndrome and Parkes Webber syndrome 2523
Disseminated hemangiomatosis 2523
Phlebectasias 2523
Vascular Ehlers–Danlos syndrome 2523
Clinical manifestations 2523
Diagnosis and treatment of gastrointestinal bleeding 2523
Prognosis 2524
Pseudoxanthoma elasticum 2524
Angiosarcomas 2524
Hemangiopericytomas 2525
Hemangioendotheliomas 2525
Further readings 2525
CHAPTER 128: Intestinal ischemia and vasculitides 2526
Definition 2526
Acute mesenteric ischemia 2527
Relevant anatomic considerations 2527
Physiology and pathophysiology 2527
Epidemiology and risk factors 2528
Clinical presentation and natural history 2528
Differential diagnosis 2529
Diagnosis 2529
Treatment 2532
Chronic mesenteric ischemia 2533
Relevant anatomic and pathophysiological considerations 2533
Clinical presentation and natural history 2534
Differential diagnosis 2535
Diagnostic procedures and approach 2535
Treatment of chronic mesenteric ischemia 2536
Ischemic colitis 2537
Epidemiology and risk factors 2537
Pathogenesis 2538
Clinical presentation 2539
Treatment of ischemic colitis 2541
Prognosis 2541
Vasculitis 2541
Degos disease 2542
Buerger disease 2542
Behçet disease 2542
Takayasu arteritis 2542
Chronic periaortitis 2543
Fibromuscular dysplasia 2543
Intestinal vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus or other systemic autoimmune disorders 2543
Polyarteritis nodosa 2543
Cogan syndrome 2543
Henoch-Schönlein purpura 2543
Churg–Strauss syndrome 2544
Further reading 2544
CHAPTER 129: Radiation injury in the gastrointestinal tract 2545
Radiation pathobiology 2545
Pathology 2548
Specific organ involvement 2551
Esophagus 2551
Stomach 2552
Small bowel 2552
Colon and rectum 2554
Liver 2555
Further reading 2556
CHAPTER 130: Complementary and alternative medicine in gastroenterology 2557
Liver disease 2557
Vitamin E 2557
Silymarin (milk thistle) 2558
Betaine 2558
Glutathione and glutathione prodrugs 2558
Polyenylphosphatidylcholine 2558
Glycyrrhizin 2559
Zinc 2559
Herbs 2559
Pancreatic disease 2559
Acupuncture 2559
Probiotics 2559
Antioxidants 2560
Transcranial magnetic stimulation 2560
Peptic ulcer disease, functional dyspepsia, H. pylori 2560
Acupuncture 2560
Probiotics and herbal therapies 2560
Irritable bowel syndrome 2561
Prebiotics and probiotics 2561
Acupuncture 2562
Herbal therapies 2562
Chinese herbal agents 2563
Inflammatory bowel disease 2563
Probiotics 2563
Helminthic parasites 2563
Prebiotics/complex carbohydrates 2564
Nicotine 2564
Transforming growth factor-? 2564
Green tea 2564
Fish oil 2564
Botanical derivatives 2565
Diarrheal illnesses 2565
Antibiotic-associated diarrhea 2565
Infectious diarrhea 2565
HIV/AIDS associated diarrhea 2566
Safety 2566
Further reading 2567
PART 5: Diagnostic and therapeutic modalities in gastroenterology 2569
A Endoscopic 2571
CHAPTER 131: General approach to endoscopy: sedation, monitoring, and preparation 2571
Introduction 2571
Continuum of depth of sedation 2571
Pre-sedation preparation 2571
Medication regimens 2572
Benzodiazepines 2574
Opiates 2574
Propofol 2574
Droperidol 2575
Ketamine 2575
Nitrous oxide 2575
Dexmedetomidine 2575
Combination regimens 2576
Topical anesthetics 2576
Reversal agents 2576
Use of anesthesiologists in endoscopic sedation 2577
General anesthesia 2577
Pregnancy and lactation 2577
Cardiac comorbidity 2577
Procedural monitoring 2577
Oximetry 2577
Capnography 2578
Bispectral monitoring 2578
Hemodynamic monitoring 2578
Postprocedure monitoring 2578
Complications of sedation and their management 2578
Respiratory depression 2579
Cardiac and hemodynamic complications 2579
Aspiration 2579
Cardiac arrythmias 2579
Procedure termination 2580
Training for use of sedatives 2580
Further reading 2580
CHAPTER 132: Upper gastrointestinal endoscopy 2581
History and background 2581
Videoendoscopes 2581
Technical considerations 2582
Before starting 2582
Introducing the endoscope 2582
The normal upper gastrointestinal endoscopic examination 2582
The use of endoscopic accessories 2584
Advanced imaging techniques 2586
Endoscopic ultrasonography 2586
Chromoendoscopy 2586
Magnification endoscopy 2587
Narrow band imaging 2588
Optical biopsy 2588
Optical coherence tomography 2588
Endoscopic confocal microscopy 2588
Therapeutic upper endoscopy 2588
Removal of foreign bodies 2588
Endoscopic control of upper gastrointestinal bleeding 2589
Polypectomy 2589
Mucosal resection 2590
Dilation 2590
Stents 2591
Laser tumor ablation 2591
Endoscopic radiofrequency ablation 2591
Safety of upper gastrointestinal endoscopy 2591
Medical history 2591
Sedation 2592
Antibiotic prophylaxis 2592
Procedure-related complications 2592
Further reading 2593
CHAPTER 133: Capsule and small bowel endoscopy 2594
Introduction 2594
Overview of capsule endoscopy 2595
Deep enteroscopy techniques 2596
Double-balloon enteroscopy 2596
Single-balloon enteroscopy 2597
Spiral enteroscopy 2597
Comparison of the diagnostic yield of deep enteroscopy techniques 2598
Obscure gastrointestinal bleeding 2598
Capsule endoscopy for obscure gastrointestinal bleeding 2598
Double-balloon enteroscopy for obscure gastrointestinal bleeding 2599
Single-balloon enteroscopy for obscure gastrointestinal bleeding 2599
Spiral enteroscopy for obscure gastrointestinal bleeding 2600
Comparison of deep enteroscopy techniques in obscure gastrointestinal bleeding 2600
Crohn’s disease 2600
Capsule endoscopy for suspected Crohn’s disease 2600
Capsule endoscopy for established Crohn’s disease 2601
Evaluation of disease distribution and activity 2601
Assessing for postoperative recurrence 2601
Evaluation of indeterminate colitis 2601
Assessing for mucosal healing and response to medications 2601
Risks and limitations of capsule endoscopy in Crohn’s disease 2601
Deep enteroscopy techniques 2602
Small bowel tumors 2602
Capsule endoscopy for small bowel tumors 2602
Small bowel polyps and polyposis syndromes 2602
Capsule endoscopy for small bowel polyps 2602
Deep enteroscopy 2602
Celiac disease 2602
Capsule endoscopy for celiac disease 2602
Deep enteroscopy for celiac disease 2603
Deep enteroscopy in endoscopic retrograde cholangiopancreatography 2603
New techniques and innovations on the horizon 2603
Conclusion 2604
Acknowledgment 2604
Further reading 2604
CHAPTER 134: Colonoscopy and flexible sigmoidoscopy 2605
Instrumentation 2605
Colonoscopy anatomy 2605
Preparation and medication use for colonoscopy 2607
Bowel cleansing 2607
Management of antithrombotic agents 2607
Sedation 2607
Antibiotics 2608
Colonoscopic technique 2608
Colonoscopy assistants 2609
Indications for colonoscopy 2609
Screening for polyps 2609
Polyp surveillance 2610
Flexible sigmoidoscopy and colonoscopy: use in diagnosis 2610
Sigmoidoscopy 2610
Colonoscopy 2610
Flexible sigmoidoscopy and colonoscopy: use in therapeutics 2611
Polyps 2611
Rectal bleeding 2612
Colonic obstruction 2612
Foreign body removal 2613
Delivery of “therapeutic microbiome” 2613
Colonoscopic findings 2613
Polyps and cancer 2613
Colitis 2613
Contraindications, alternatives and limitations of colonoscopy 2614
Low-yield indications 2614
Contraindications 2614
Limitations 2614
Alternatives 2614
Complications of colonoscopy 2614
Bleeding 2614
Perforation 2615
Sedation-related 2615
Sepsis 2615
Costs 2615
Emerging and future developments in colonoscopy 2615
Toward better inspection of the colonic surface 2615
Toward closer study of observed lesions 2616
Toward making colonoscopy more therapeutic 2616
Toward making colonoscopy easier for the patient 2616
Toward making colonoscopy easier for the endoscopist 2616
Further reading 2617
CHAPTER 135: Endoscopic retrograde cholangiopancreatography 2618
Introduction 2618
Indications for endoscopic retrograde cholangiopancreatography 2618
Complications of endoscopic retrograde cholangiopancreatography 2619
Therapeutic and diagnostic techniques 2623
Sphincterotomy and balloon dilation 2625
Prosthetic stent placement 2625
Cholangioscopy 2626
Biliary diseases 2627
Bile duct stones 2627
Role of endoscopic retrograde cholangiopancreatography in disease associated with gallstone disease 2632
Biliary leaks 2632
Biliary strictures 2633
Endoscopic retrograde cholangiopancreatography after liver transplantation 2639
Ampullary tumors 2640
Endoscopic retrograde cholangiopancreatography in pancreatic disease 2641
Acute pancreatitis 2641
Chronic pancreatitis 2644
Endoscopic retrograde cholangiopancreatography in surgically altered upper gastrointestinal anatomy 2646
Further reading 2647
CHAPTER 136: Gastrointestinal dilation and stent placement 2648
Introduction 2648
Dilation 2648
Theoretical considerations 2648
Technical applications 2650
Indications and contraindications 2651
Risks and alternatives 2652
Efficacy 2653
Stent placement 2654
Theoretical considerations 2654
Technical application 2656
Indications and contraindications 2658
Risks and alternatives 2659
Efficacy 2660
Future applications 2661
Further reading 2662
CHAPTER 137: Endoscopic approaches to enteral nutrition 2663
Introduction 2663
Types of endoscopic enteral feeding 2663
Transnasal feeding 2663
Percutaneous options for feeding 2664
Percutaneous endoscopic gastrostomy 2664
Patient preparation 2664
Supplies for percutaneous endoscopic gastrostomy placement 2665
Pull (Ponsky–Gauderer) technique 2665
Push (Sacks–Vine) technique 2666
Direct introducer (Russell) technique 2666
Radiologically placed gastrostomy 2667
Surgically placed gastrostomy 2667
Comparison of gastrostomy techniques 2667
Postprocedural management 2668
Complications 2668
Aspiration 2668
Wound infection 2669
Pneumoperitoneum and peritonitis 2669
Gastrocolocutaneous fistula 2669
Buried bumper syndrome 2669
Neoplastic seeding of the stoma 2670
Use of gastrostomy tubes and sites for endoscopic jejunostomy 2670
Direct percutaneous endoscopic jejunostomy tube placement 2670
Conclusion 2671
Further reading 2671
CHAPTER 138: Management of upper gastrointestinal hemorrhage related to portal hypertension 2672
Introduction 2672
Anatomy of portal venous system (see Chapter 10) 2672
Causes of portal hypertension 2673
Portal venous imaging techniques and measurement of portal pressure 2673
Pathophysiology of portal hypertension 2675
Endothelial dysfunction in intrahepatic circulation 2676
Endothelial dysfunction in splanchnic and systemic circulations 2676
Strategies for the long-term treatment of portal hypertension 2676
Gastroesophageal varices 2678
Gastric varices 2690
Secondary prophylaxis 2694
Gastric varices prevention 2697
Portal hypertensive gastropathy and gastric antral vascular ectasia 2698
Ectopic varices 2699
Acknowledgments 2699
Further reading 2699
CHAPTER 139: Endoscopic diagnosis and treatment of nonvariceal upper gastrointestinal hemorrhage 2700
Introduction 2700
Initial assessment 2700
Identifying the source of bleed 2701
Proton pump inhibitor (PPI) use 2701
The role of endoscopy 2702
Peptic ulcer disease 2703
Modalities of endoscopic treatment 2705
Epinephrine injection 2705
Sclerosants and absolute ethanol injection 2706
Tissue adhesive therapy 2706
Mechanical therapy 2706
Thermal coagulation devices (Figure 139.2a–d) 2707
Novel endoscopic hemostasis devices 2708
Other nonulcer upper gastrointestinal bleeding 2710
Esophagitis (Figure 139.6a) 2710
Dieulafoy’s lesion (Figure 139.6b) 2711
Mallory Weiss tear (Figure 139.6c) 2711
Gastric antral vascular ectasia (GAVE) (Figure 139.6d) 2711
Gastrointestinal tumors (Figure 139.6e) 2712
Second look endoscopy 2712
Post endoscopic management 2713
Summary 2713
Further reading 2713
CHAPTER 140: Endoscopic therapy for polyps and tumors 2714
Methods of endoscopic therapy 2714
Polypectomy 2714
Endoscopic mucosal resection 2716
Endoscopic submucosal dissection 2717
Submucosal endoscopy 2718
Additional tools for endoscopic lesion removal 2719
Endoscopic clips 2719
Detachable loops 2719
Argon plasma coagulation 2720
Endoscopic tissue tattooing 2720
Complications of endoscopic therapy 2721
Esophageal lesions 2721
Ablation for high-grade dysplasia 2721
Endoscopic resection for high-grade dysplasia 2721
Endoscopic resection for early esophageal cancer 2722
Palliation of advanced esophageal cancer 2723
Gastric lesions 2723
Hyperplastic and adenomatous polyps 2723
Duodenal lesions 2724
Colorectal polyps and tumors 2725
Diminutive polyps 2725
Small and large polyps 2725
Nonpedunculated large polyps ?20 mm 2725
Pedunculated polyps 2727
Endoscopic treatment of colorectal cancers 2727
Further reading 2728
CHAPTER 141: Laparoscopy and laparotomy 2729
Introduction 2729
Evolution of modern laparoscopy 2729
Indications for diagnostic laparoscopy and laparotomy 2730
Staging laparoscopy for intraabdominal malignancies 2730
Acute abdomen 2731
Diagnostic laparoscopy in the intensive care unit 2731
Diagnostic and therapeutic laparoscopy for trauma 2733
Technique for diagnostic laparoscopy 2734
Technique for explorative laparotomy 2734
Complications of laparoscopy and laparotomy 2734
Complications of the laparoscopic access 2735
Effects of CO2 pneumoperitoneum 2735
Vascular injury 2736
Visceral damage 2736
Gas embolism 2736
Laparoscopy in the pregnant patient 2736
Future of emerging diagnostic methods 2736
Single-port surgery 2736
Minilaparoscopy 2737
Conclusion 2738
Further reading 2738
CHAPTER 142: Submucosal endoscopy 2739
Prelude to submucosal endoscopy 2739
Submucosal endoscopy 2740
The SEMF method 2741
SEMF for diagnosis 2742
Submucosal endoscopy with mucosal resection (SEMR) 2743
Other uses for submucosal endoscopy 2744
Further reading 2744
CHAPTER 143: Natural orifice translumenal endoscopic surgery (NOTES) 2745
Potential benefits of NOTES over current surgical techniques 2746
Closure of the gastrointestinal wall after NOTES 2746
Risk of infection in NOTES 2748
NOTES: current status and human experience 2749
Transesophageal NOTES 2749
Transgastric NOTES 2750
Transvaginal NOTES 2750
Transrectal NOTES 2752
Transvesical NOTES 2752
Future applications of NOTES 2752
NOTES echoendoscopy 2752
Real-time image-guided NOTES 2752
NOTES for retroperitoneal disease 2753
Transgastric gastrojejunostomy 2753
Transoral thyroidectomy 2753
Transgastric splenectomy and hernia repair 2754
Transgastric fallopian tube ligation 2754
Transgastric pelvic organ resection 2754
Peritoneal interventions in the intensive care unit 2754
Acute management of blunt trauma 2754
NOTES in autopsies 2755
NOTES: evolving beyond the traditional operating room 2755
Robots for NOTES 2755
Intrauterine fetal interventions 2755
Spinal procedures 2755
NOTES: the road toward clinical applicability 2756
Further reading 2756
B Imaging 2757
CHAPTER 144: Plain and contrast radiology 2757
Abdominal radiographs 2757
Technique 2757
Abnormalities 2757
Contrast studies 2761
Pharynx 2761
Upper gastrointestinal tract 2764
Small bowel 2770
Colon 2774
Further reading 2777
CHAPTER 145: Abdominal sonography 2778
Introduction 2778
Basic principles of diagnostic ultrasound 2778
Gray scale imaging 2778
Doppler imaging 2779
Equipment 2780
Limitations with respect to the other imaging modalities 2780
Liver 2780
Indications for sonography 2780
Anatomy 2781
Ultrasound technique 2781
Focal liver masses 2781
Diffuse parenchymal disease 2784
Hepatic vascular disease 2785
Bile ducts 2787
Anatomy 2787
Ultrasound technique 2787
Biliary obstruction 2788
Pneumobilia 2789
Inflammatory processes of the biliary tree 2789
Gallbladder 2790
Anatomy 2790
Ultrasound technique 2790
Cholelithiasis and sludge 2790
Cholecystitis 2790
Gallbladder polyps 2791
Adenomyomatosis 2792
Porcelain gallbladder 2792
Gallbladder carcinoma 2792
Pancreas 2793
Anatomy 2793
Ultrasound technique 2793
Pancreatitis 2794
Pancreatic tumors 2794
Gastrointestinal tract 2795
Anatomy 2795
Ultrasound technique 2795
Indications 2795
Appendicitis 2795
Intussusception 2796
Other causes of bowel wall thickening 2796
Peritoneal cavity 2796
Intraperitoneal fluid 2796
Intraperitoneal fluid collections 2797
Peritoneal masses 2797
Intraoperative sonography 2797
Further reading 2798
CHAPTER 146: Endoscopic ultrasonography 2799
Introduction 2799
Technical considerations 2799
Basic properties of sound waves 2799
Components of an echoendoscope 2800
Principles of imaging 2800
Equipment 2801
Radial echoendoscopes 2801
Linear echoendoscopes 2801
Catheter probes 2801
FNA needles and techniques 2802
Diagnostic EUS general considerations 2803
Diagnostic EUS Indications 2804
Esophageal cancer 2804
Submucosal lesions 2806
Stomach 2808
Ampullary and pancreatic neoplasms 2809
Chronic pancreatitis 2813
Pancreatic cysts and intraductal papillary mucinous neoplasms 2814
Biliary tract indications and cholangiocarcinoma 2815
Lung cancer 2816
Interventional EUS 2817
Background 2817
EUS-guided biliary drainage (EUS-BD) 2818
EUS-guided pancreatic duct interventions 2821
EUS-guided celiac plexus neurolysis 2823
EUS-guided fiducial placement 2823
EUS-guided angiotherapy 2824
Conclusion 2825
Author disclosure 2825
Further reading 2825
CHAPTER 147: Computed tomography of the gastrointestinal tract 2826
Introduction 2826
The hollow viscera of the gastrointestinal tract 2826
Techniques 2826
Esophagus 2828
Stomach 2829
Small intestine 2831
Colon 2834
Solid organs of the gastrointestinal tract 2838
Liver 2838
Pancreas 2843
Biliary tract 2848
Peritoneum 2851
Neoplasms 2851
Nonneoplastic peritoneal diseases 2852
Hernias 2853
Further readings 2854
CHAPTER 148: Magnetic resonance imaging 2855
Introduction 2855
Basic principles (Table 148.1) 2856
Liver (Table 148.2) 2859
Benign lesions 2860
Biliary tree 2873
Cholangiocarcinoma 2873
Pancreas 2873
Normal anatomy and variants 2873
Chronic pancreatitis 2875
Trauma 2876
Neoplasms 2876
Gallbladder 2881
Magnetic resonance cholangiopancreatography (MRCP) 2882
Benign cystic disease 2883
Congenital variants of the biliary system 2883
Pancreas divisum 2884
Cholelithiasis 2884
Choledocholithiasis 2884
Primary sclerosing cholangitis 2884
Postsurgical biliary complications 2885
Chronic pancreatitis 2886
Cholangiocarcinoma 2886
Pancreatic cancer 2887
Intestine 2887
MR of the small bowel 2887
MR colonography 2889
MRI of perianal fistula 2890
Further reading 2891
CHAPTER 149: Positron emission tomography 2892
Introduction 2892
Basic principles 2892
PET scanners 2893
Scanner basics 2893
PET-CT and attenuation correction 2894
Time of flight PET 2894
PET-MRI 2894
PET radiotracers 2894
2-Deoxy-2-[18F]fluoro-D-glucose (FDG) 2895
Clinical applications of PET in gastroenterology 2895
Colorectal cancer 2896
Esophageal cancer 2898
Pancreatic cancer 2899
Hepatic imaging 2900
Neuroendocrine tumors 2900
GIST 2901
Other diseases 2901
Non-FDG PET 2902
Future directions 2902
Further reading 2902
CHAPTER 150: Radionuclide imaging in the gastrointestinal tract 2903
Introduction 2903
Radiopharmaceuticals 2903
Radiation detection instrumentation 2903
Common gastrointestinal nuclear medicine studies 2904
Cholescintigraphy 2904
Tc-99m labeled red blood cells – cavernous hemangioma of the liver 2911
Tc-99m sulfur colloid liver–spleen scanning 2911
Gastrointestinal motility 2912
Gastrointestinal bleeding 2915
Meckel’s diverticulum and ectopic gastric mucosa 2918
Inflammatory bowel disease – Fluorine-18 fluorodoxyglucose 2918
Somatostatin receptor imaging of neuroendocrine tumors – octreoscan 2918
Fluorine-18 fluorodoxyglucose PET/CT imaging of gastrointestinal malignancies 2919
Further reading 2921
CHAPTER 151: Abdominal angiography 2922
Technical considerations 2922
Percutaneous catheterization 2923
General angiographic approach 2923
Wedged hepatic venography and manometry 2924
Transhepatic portal vein catheterization 2924
Transjugular portal vein catheterization 2924
Splenoportography and percutaneous transsplenic portal vein catheterization 2924
Risks and contraindications 2925
Vascular anatomy of the abdominal viscera 2925
Arterial vasculature 2925
Portal venous system 2927
Hepatic veins 2928
Arterial disease 2929
Acute mesenteric ischemia 2929
Colonic ischemia 2930
Intestinal angina 2930
Celiac axis compression 2930
Superior mesenteric artery syndrome 2931
Vasculitis 2931
Splanchnic artery aneurysms and pseudoaneurysms 2931
Abdominal trauma 2932
Venous disease 2932
Portal vein occlusion 2932
Splenic vein occlusion 2933
Budd–Chiari syndrome 2933
Gastrointestinal disease 2934
Upper gastrointestinal bleeding 2934
Lower gastrointestinal bleeding 2935
Angiodysplasia 2935
Meckel diverticulum 2936
Rectal trauma 2936
Intestinal varices 2936
Neoplasms of the small intestine 2936
Pancreatic disease 2937
Adenocarcinoma 2937
Cystic tumors 2937
Pancreatic endocrine tumors 2937
Pancreatic arteriovenous malformations 2939
Vascular lesions associated with pancreatitis 2939
Hepatic disease 2939
Cavernous hemangiomas 2940
Adenoma 2940
Focal nodular hyperplasia 2940
Biliary cystadenoma 2940
Hepatocellular carcinoma 2940
Cholangiocarcinoma 2941
Metastatic hepatic neoplasms 2941
Panhepatic angiography 2941
Percutaneous transcatheter therapy 2941
Percutaneous translumenal angioplasty and stent placement 2942
Transcatheter embolotherapy 2942
Thrombolytic therapy 2942
Hepatic arterial infusion chemotherapy 2942
Hepatic tumor embolization 2942
Forthcoming advances 2944
Further reading 2944
CHAPTER 152: Interventional radiology 2945
Introduction 2945
Treatment of primary and secondary liver cancer 2945
Ablative therapies 2945
Intraarterial therapies 2947
Clinical evidence 2952
Vascular interventions 2954
Introduction 2954
GI tract bleeding 2954
Acute mesenteric ischemia 2958
Chronic mesenteric ischemia 2959
Abdominal visceral artery aneurysm 2960
Inferior vena cava disorders 2961
Transjugular intrahepatic portosystemic shunt and portal vein interventions 2963
Introduction 2963
Transjugular intrahepatic portosystemic shunt (TIPS) 2963
Budd–Chiari syndrome 2966
Portal vein interventions 2966
Biliary interventions in interventional radiology 2967
Introduction 2967
Percutaneous transhepatic cholangiography and biliary drainage 2967
Percutaneous transhepatic management of malignant biliary obstruction 2968
Percutaneous transhepatic management of benign biliary strictures 2969
Percutaneous management of biliary stones 2971
Percutaneous gallstones treatment 2971
Percutaneous intra/extrahepatic biliary stones treatment 2971
Percutaneous cholecystostomy 2971
Technique 2972
Outcomes and complications 2972
Postprocedure care 2973
Percutaneous management of bile leakage 2973
Percutaneous gastric, gastrojejunostomy and jejunostomy feeding tubes 2973
Introduction 2973
Indications 2973
GI decompression 2974
Contraindications (Box 152.5) 2974
Preprocedure 2975
Technique 2975
Outcomes 2975
Complications 2975
Postprocedural and follow-up care 2975
Percutaneous image-guided biopsy 2975
Preprocedure 2975
Postprocedure care 2976
Outcomes 2976
Complications 2976
Transjugular liver biopsy 2976
Outcomes 2977
Drainage of abdominal collections 2977
Preprocedure 2977
Outcomes 2977
Complications 2978
Further reading 2978
CHAPTER 153: Confocal laser microscopy 2980
Introduction 2980
Technical aspects 2980
Clinical applications 2981
Esophagus 2981
Stomach 2982
Duodenum and small bowel 2982
Biliary and pancreatic system 2982
Cystic or solid lesions 2982
Colon 2983
Molecular imaging 2984
Summary 2984
Further reading 2985
C Pathology 2986
CHAPTER 154: Liver biopsy and histopathological diagnosis 2986
Introduction 2986
Technique of liver biopsy 2986
Needle types 2987
Imaging for liver biopsy 2987
Surgical approaches 2987
Percutaneous approach 2987
Adequacy of specimen 2988
Complications 2988
Alternatives to liver biopsy 2988
Processing of liver biopsy tissues 2989
Special requirements 2989
Systematic approach to the review of liver biopsies 2990
Portal areas 2990
Terminal hepatic venules 2992
Hepatic parenchyma 2994
Parenchymal inclusions 2995
Cord pattern 2996
Nuclear changes 2996
Sinusoidal spaces and lining cells 2996
Cholestasis 2999
Fat 2999
Terminal hepatic venules and venous outflow 2999
Space-occupying lesions of the liver 3000
Primary tumors: benign and malignant 3000
Nodular regenerative hyperplasia 3001
Metastatic tumors 3001
Granulomas 3002
Differential diagnosis of cirrhosis 3003
Specific liver diseases 3005
Necroinflammatory diseases 3005
Other viral infections 3007
Alcoholic liver disease 3008
Acute changes 3008
Chronic alcohol-induced liver damage 3009
Differential diagnosis 3009
NAFLD 3009
Biliary diseases 3010
PBC and primary sclerosing cholangitis 3010
Drug-induced liver injury 3011
Parenchymal changes 3011
Portal tract changes 3012
Vascular changes 3012
Liver biopsy changes in systemic diseases 3012
Acquired immunodeficiency syndrome 3013
Pathology of transplantation 3014
Allograft rejection 3014
Harvest or preservation injury 3014
Cytomegalovirus hepatitis 3014
Recurrent hepatitis B in allograft 3015
Recurrent hepatitis C 3015
Recurrent AIH, PBC and PSC 3015
Further reading 3015
CHAPTER 155: Endoscopic mucosal biopsy – histopathological interpretation 3016
General principles of gastrointestinal biopsy interpretation 3016
Overview comments on the GI tract 3016
Sampling 3017
Esophagus 3017
Nonneoplastic and benign polyps 3017
Esophagitis caused by infectious agents 3022
Polyps 3024
Barrett esophagus 3025
Tumors 3029
Stomach 3031
Inflammatory disorders 3031
Hyperplastic gastropathy 3036
Small bowel 3047
Nonneoplastic conditions 3047
Small bowel – polyps and neoplasms 3056
Polyps (adenomas, Peutz-Jehgers polyp) 3056
Lymphomas 3057
Well differentiated neuroendocrine (carcinoid) tumors of small bowel 3060
Mesenchymal tumors 3061
Colon 3061
Nonneoplastic conditions 3061
Effects of bowel preparation and other artifacts 3062
Other endoscopic and biopsy-related artifacts 3062
Focal active colitis 3062
Lamina propria macrophages 3062
Ulcerative colitis 3063
Crohn’s disease 3064
Pouchitis 3065
Infectious colitis 3066
Ischemic colitis 3068
Diversion colitis 3073
Colon – polyps and neoplasms 3073
Pathologic evaluation and diagnosis of early colorectal cancers treatable by endoscopic polypectomy 3078
Small-cell carcinomas of the colon 3080
Serrated polyps 3080
Colitis 3082
Anus 3085
Nonneoplastic 3085
Polyps 3086
Neoplasia 3087
Mesenchymal tumors 3092
Further reading 3093
D Gastrointestinal function studies 3094
CHAPTER 156: Tests of gastric and pancreatic function and absorption 3094
Gastric secretory testing 3094
Physiology of gastric acid secretion 3094
Gastric hormonal and secretory testing 3094
Gastric acid secretory testing 3099
Pancreatic function testing 3102
Exocrine pancreas 3102
Endocrine pancreas 3103
Further reading 3105
Subject index 3107
EULA 3259
"In short, this is an invaluable book, and a must for every gastroenterologist's practice. The content is exceptional, with detailed information on nearly all subspecialties in gastroenterology and quality images, including endoscopic pictures, for reference. Pairing the print version with the website is critical for keeping material relevant and accessible today. Dr. Yamada is a leader in the field of gastroenterology, and this book is an unparalleled contribution." (Doody Enterprises 15.03.2017)
| Erscheint lt. Verlag | 13.10.2015 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Allgemeines / Lexika |
| Medizinische Fachgebiete ► Innere Medizin ► Gastroenterologie | |
| Schlagworte | Gastroenterologie • Gastroenterologie u. Hepatologie • Gastroenterology & Hepatology • Gastroenterology, Liver Disease, GI Research, Autoimmune Pancreatitis, Fecal Biomarkers, Genetics, Systemic disease, Crohn’s Disease, Ulcerative Colitis, Eosinophilic Esophagitis. • Gastrointestinal surgery • Hepatologie • hepatology • Magen-Darm-Chirurgie • Medical Science • Medizin |
| ISBN-13 | 9781118512159 / 9781118512159 |
| Informationen gemäß Produktsicherheitsverordnung (GPSR) | |
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PDF (Adobe DRM)Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
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