Sleisenger and Fordtran's Gastrointestinal and Liver Disease

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Cleaned version with corrected pagination and bookmarks as well as removed watermarks. Cover Sleisenger and Fordtran’s Gastrointestinal and Liver Disease Copyright Dedication Contributors Foreword The Sleisenger and Fordtran Editors Preface Acknowledgments Abbreviation List Part I: Biology of the Gastrointestinal Tract Chapter 1: Cellular Growth and Neoplasia Mechanisms of Normal Tissue Homeostasis Cellular Proliferation Apoptosis Senescence Signaling Pathways That Regulate Cellular Growth Intestinal Tumor Development Multistep Formation Clonal Expansion Cancer Stem Cells Epithelial-Mesenchymal Transition Neoplasia-Associated Genes Oncogenes Oncogenic Growth Factors and Growth Factor Receptors Signal Transduction–Related Oncogenes Nuclear Oncogenes Tumor Suppressor Genes Adenomatous Polyposis Coli Gene TP53 Gene SMAD4 Gene DNA Repair Genes Noncoding RNAs Oncogenic Signaling Pathways Tumor Microenvironment Tumor Metabolism Inflammation and Cancer Microbiome Biological Features of Tumor Metastasis Angiogenesis and Lymphangiogenesis Environmental Influences Chemical Carcinogenesis Dietary Factors Molecular Medicine: Current and Future Approaches in Gastrointestinal Oncology Next Generation Sequencing Cancer and Tumor Genomics Molecular Diagnostics Chapter 2: Mucosal Immunology and Inflammation Immunoglobulins of the Mucosal Surface Physiology of Mucosal Immune Cells Functional Anatomy of the Mucosal Immune System Peyer Patches and M Cells Intestinal Epithelial Cells Paneth cells Goblet Cells Tuft Cells Recognition of Pathogen-Associated Molecular Patterns by Pattern Recognition Receptors Antigen Presentation in the Gut Effector Compartments within the Gut Immune System Intraepithelial Lymphocytes Lamina Propria Lymphocytes and Mononuclear Cells T Cell Differentiation Innate Lymphoid Cells Dendritic Cells Macrophages Oral Tolerance Chemokine Role in Homeostasis and Inflammation Chapter 3: The Enteric Microbiota Characteristics of the Human Intestinal Microbiome Spatial Variation in the Intestinal Microbiome Temporal Changes and Resilience of the Intestinal Microbiome Factors Affecting Intestinal Microbiome Variability and Resilience Age Sex Genetics Geography and Diet Exercise Medications Other Lifestyle Factors Microbe-Microbe Signaling The Effect of Host–Intestinal Microbiome Interactions on Host Physiology Interactions Between the Intestinal Microbiome and Immune System Interactions Between the Intestinal Microbiome and Gastrointestinal Tract The Microbiome-Gut-Brain Axis The role of the intestinal microbiome in human disease Metabolic Function Inflammatory Diseases Cancer Functional Gastrointestinal Disorders The role of the Intestinal Microbiome in Modulation of Drug Response Therapeutic Modulation of the Intestinal Microbiome NonBacterial Members of the Intestinal Microbiome Future Directions Chapter 4: Gut Sensory Transduction Hormones and Neurotransmitters Defining Hormones and Neurotransmitters Modes of Transmitter Release Transducing Signals from the GI Lumen Recognizing Signals Through Cell Surface Receptors G Protein–Coupled Receptors Enzyme-Coupled Receptors Ion Channel–Coupled Receptors Nutrient Chemosensing Lipids Proteins and Amino Acids Tastants Sensing the Microbiome Other Factors Stimulating Transmitter Release The Transmitters Gut Neuropeptides Gastrin Cholecystokinin Secretin Vasoactive Intestinal Polypeptide Glucagon Glucose-Dependent Insulinotropic Polypeptide Pancreatic Polypeptide Family Substance P and the Tachykinins Somatostatin Motilin Leptin Ghrelin Neurotransmitters Acetylcholine Catecholamines Dopamine Serotonin Histamine Nitric oxide Cannabinoids and other Chemical Transmitters Cannabinoids Adenosine Cytokines The Importance of Hormones and Neurotransmitters Growth and Abnormal Growth of the Gut Growth Factor Receptors Epidermal Growth Factor Transforming Growth Factor-α Transforming Growth Factor-β Insulin-Like Growth Factors Fibroblast Growth Factor and Platelet-Derived Growth Factor Trefoil Factors Diabetes and the Gut Gastrointestinal Regulation of Appetite Part II: Nutrition in Gastroenterology Chapter 5: Nutritional Principles and Assessment of the Gastroenterology Patient Basic Nutritional Concepts Energy Stores Energy Metabolism Resting Energy Expenditure Energy Expenditure of Physical Activity Thermic Effect of Feeding Recommended Energy Intake in Hospitalized Patients Methods Incorporating Metabolic Stress Factors Method Without a Stress Factor Caloric Delivery and Avoidance of Hyperglycemia Proteins Nitrogen Balance Carbohydrates Lipids Essential Fatty Acids Major Minerals Micronutrients Vitamins Trace Minerals Physiologic and Pathophysiologic Factors Affecting Micronutrient Requirements Age Malabsorption and Maldigestion Starvation Malnutrition Protein-Energy Malnutrition (PEM) Primary Versus Secondary Protein-Energy Malnutrition: A Body Compartment Perspective Protein-Energy Malnutrition in Children Kwashiorkor Marasmus Nutritional Dwarfism Physiologic Impairments Caused by Protein-Energy Malnutrition System Effects Gastrointestinal Tract Cardiovascular System Immune System Respiratory System Endocrine System Other Effects Wound Healing Skin Hair Kidneys Bone Marrow Nutritional Assessment Techniques History Weight Loss Food Intake Evidence of Malabsorption Evidence of Specific Nutrient Deficiencies Influence of Disease on Nutrient Requirements Functional Status Physical Examination Hydration Status Tissue Depletion Muscle Function Specific Nutrient Deficiencies Anthropometry Functional Measures of Protein-Calorie Status Biochemical Measures of Protein-Calorie Status Serum Proteins Creatinine-Height Index Discriminant Analyses of Protein-Calorie Status Rapid Screening Tools for Assessment of Targeted Populations Subjective Global Assessment Mini-Nutritional Assessment Aggressive Nutritional Support in the Hospitalized Patient Malnourished Patients Undergoing Major Surgery Patients Hospitalized with Decompensated Alcohol-Associated Liver Disease Patients Undergoing Radiation Therapy Chapter 6: Nutritional Management Nutrition in Specific Disease States Intestinal Failure Pancreatitis Crohn Disease (CD) Liver Disease Diverticular Disease Dumping Syndrome Cancer Obesity Critical Illness Nutritional Therapy Enteral Nutrition Nasoenteric Tube Access Percutaneous Endoscopic Enteral Access Indications for Percutaneous Access Devices Cancer Stroke Dementia Percutaneous Endoscopic Gastrostomy Percutaneous Endoscopic Gastrojejunostomy Direct Percutaneous Jejunostomy Complications Enteral Feeding Enteral Formulations Complications of Enteral Feeding Parenteral Nutrition Parenteral Nutrition Formulation Administration Laboratory Testing Metabolic Complications Vascular Access Devices Central Venous Catheter Complications Special Diets Chapter 7: Obesity Definitions and Epidemiology Etiology of Obesity Dietary Factors Physical Activity Factors In-Utero and Maternal Factors Medication-Induced Weight Gain Smoking Microbiome Genetics Prognosis of Obesity Pathophysiology of Obesity Clinical Features and Diagnosis of Obesity History and Physical Examination Complications of Obesity Diabetes Lipid Derangements Cardiovascular Diseases Hypertension Kidney Disease Gallbladder Disease Liver Disease Gastroesophageal Reflux Disease (GERD) Cancer Obstructive Sleep Apnea Diseases of the Bones, Joints, Muscles, Connective Tissue, and Skin Psychosocial Dysfunction Medical Treatment of Obesity Dietary Approaches Low-Fat Diets (LFDs) Low-Carbohydrate Diets (LCDs) Meal-Replacement Diets Mediterranean Diet (MD) Intermittent Fasting Pharmacotherapy Phentermine/Topiramate Lorcaserin Bupropion/Naltrexone Liraglutide Orlistat Investigational Approaches Chapter 8: Surgical and Endoscopic Treatment of Obesity Evaluation and Selection of Bariatric Surgery Candidates Surgical Treatments for Obesity Gastric Bypass Sleeve Gastrectomy Other Operations Surgical Complications Nutritional Deficiencies Outcomes Endoscopic Management of Bariatric Surgical Complications Ulceration Postoperative Gastrointestinal Bleeding Stenosis Foreign Body Complications Leaks and Fistulae Pancreaticobiliary Disease Weight Regain and Dilated Gastrojejunal Anastomosis Endoscopic Treatments for Obesity Evaluation and Selection of Endoscopic Bariatric Therapy Candidates Endoscopic Bariatric Therapies Currently Performed in the USA Intragastric Balloons Aspiration Therapy Device Endoscopic Sleeve Gastroplasty Endoscopic Bariatric Therapy Complications Intragastric Balloons Aspiration Therapy Endoscopic Sleeve Gastroplasty Nutritional Deficiencies Outcomes Intragastric Balloons Aspiration Therapy Endoscopic Sleeve Gastroplasty Chapter 9: Feeding and Eating Disorders Epidemiology Causative Factors Satiety Appetite Energy Storage Onset and Course Evaluation Diagnosis of Specific Disorders Anorexia Nervosa Bulimia Nervosa Binge-Eating Disorder Other Specified Feeding or Eating Disorder and Unspecified Feeding or eating Disorder Avoidant/Restrictive Food Intake Disorder Pica Rumination Disorder Differential Diagnosis Nutritional, Medical, and Laboratory Evaluation Nutritional Evaluation Special Considerations in the Determination of Weight and Weight Status Medical Evaluation Laboratory Evaluation Gastrointestinal Abnormalities Associated With Eating Disorders Functional Gastrointestinal Disorders Esophageal Symptoms Liver Abnormalities Pancreas Complications Superior Mesenteric Artery Syndrome Gastric Motility Constipation Medications and Dietary Supplements Other Life-Threatening Gastrointestinal Complications Gastrointestinal Complications in Other Feeding and Eating Disorders Management of Eating Disorders in the Adult Psychiatric Treatment Psychotherapeutic Options Pharmacotherapy Nutritional Rehabilitation Medical Management of Gastrointestinal Symptoms Eating Disorders and the Intestinal Microbiota Chapter 10: Food Allergies Definitions Prevalence Pathogenesis Clinical features Immunoglobulin E-Mediated Disorders Pollen-Food Allergy Syndrome Gastrointestinal Allergy Mixed Immunoglobulin E- and Non–Immunoglobulin E-Mediated Disorders Eosinophilic Esophagitis Eosinophilic Gastroenteritis Allergic Eosinophilic Proctocolitis Infantile Colic Non–Immunoglobulin E-Mediated Disorders Food Protein-Induced Enterocolitis Syndrome Food Protein-Induced Enteropathy Celiac Disease Dermatitis Herpetiformis Other Gastrointestinal Disorders Diagnosis Prevention Treatment and natural history Part III: Symptoms, Signs, and Biopsychosocial Issues Chapter 11: Acute Abdominal Pain Anatomy and Physiology Visceral Pain Somatic-Parietal Pain Referred Pain Evaluation Approach to Acute Care History Chronology Location Intensity and Character Aggravating and Alleviating Factors Associated Symptoms Past Medical History Physical Examination Abdominal Examination Genital, Rectal, and Pelvic Examinations Laboratory Data Imaging Studies CT US Other Diagnostic Tests Causes Acute Appendicitis Acute Biliary Disease SBO Acute Diverticulitis Acute Pancreatitis Perforated Peptic Ulcer Acute Mesenteric Ischemia Abdominal Aortic Aneurysm Abdominal Compartment Syndrome Other Intra-abdominal Causes Extra-abdominal and Systemic Causes Special Circumstances Extremes of Age Pregnancy Immunocompromised Hosts Pharmacologic Management Chapter 12: Chronic Abdominal Pain Definition and Clinical Approach Abdominal Wall Pain Anterior Cutaneous Nerve Entrapment and Myofascial Pain Syndromes Slipping Rib Syndrome Thoracic Nerve Radiculopathy Centrally Mediated Abdominal Pain Syndrome Epidemiology Pathophysiology Ascending Visceral Pain Transmission Descending Modulation of Pain Visceral Sensitization Biochemical Role of 5-HT Role of the CNS Clinical Implications Clinical Features History Patient Behavior Physical Examination Diagnosis and Differential Diagnosis Treatment Establishing a Successful Patient-Physician Relationship Instituting a Treatment Plan Pharmacotherapy Mental Health Referral and Psychological Treatments Narcotic Bowel Syndrome/Opioid-Induced Gastrointestinal Hyperalgesia Chapter 13: Symptoms of Esophageal Disease Dysphagia Pathophysiology Differential Diagnosis and Approach Oropharyngeal Dysphagia Esophageal Dysphagia Odynophagia Globus Sensation Pathophysiology Approach Hiccups Chest pain of Esophageal Origin Pathophysiology Approach Heartburn and Regurgitation Pathophysiology Approach Extraesophageal Symptoms of Gastroesophageal Reflux Disease Chapter 14: Dyspepsia Definition Organic Causes Intolerance to Food or Drugs PUD GERD Gastric and Esophageal Cancer Biliary and Pancreatic Tract Disorders Other GI or Systemic Disorders Functional Dyspepsia Dyspepsia Symptom Complex Pattern and Heterogeneity Subgroups Overlap with Heartburn and IBS Epidemiology Pathophysiology Delayed Gastric Emptying Impaired Gastric Accommodation to a Meal Hypersensitivity to Gastric Distension Low-Grade Mucosal Inflammation in the Duodenum Altered Duodenal Sensitivity to Lipids or Acid Other Mechanisms Pathogenic Factors Genetic Predisposition Infection Hp Infection Postinfection Functional Dyspepsia Psychosocial Factors Approach to Uninvestigated Dyspepsia History and Physical Examination Laboratory Testing Initial Management Strategies Prompt Endoscopy and Directed Treatment Test and Treat for Hp Infection Empirical Antisecretory Drug Therapy Recommendations Additional Investigations Treatment of Functional Dyspepsia General Measures Pharmacologic Treatment Acid-Suppressive Drugs Eradication of Hp Infection Prokinetic Agents Agents that Enhance Gastric Accommodation Centrally Acting Neuromodulators Other Pharmacotherapeutic Approaches Psychological Interventions Recommendations Chapter 15: Nausea and Vomiting Pathophysiology Clinical Characteristics Causes Acute Vomiting Gastric Outlet Obstruction Acute Intestinal Obstruction Intestinal Infarction Infectious and Inflammatory Causes Extraintestinal Causes Medications and Toxins Metabolic Causes Neurologic Causes Postoperative Nausea and Vomiting Chronic or Relapsing Vomiting Partial Intestinal Obstruction GI Motility Disorders Neurologic Disorders Nausea and Vomiting During Pregnancy Hyperemesis Gravidarum Functional Vomiting Cyclic Vomiting Syndrome and Cannabinoid Hyperemesis Syndrome Cyclic Vomiting Syndrome Cannabinoid Hyperemesis Syndrome Superior Mesenteric Artery Syndrome Rumination Syndrome Evaluation Acute Vomiting Imaging Additional Tests Chronic Vomiting Esophageal Manometry Measurement of Gastric Emptying Cutaneous Electrogastrography Antroduodenal Manometry Autonomic Function Tests Histopathologic Studies Complications Emetic Injuries to the Esophagus and Stomach Spasm of the Glottis and Aspiration Pneumonia Fluid, Electrolyte, and Metabolic Alterations Nutritional Deficiencies Treatment Correction of Metabolic Complications Pharmacologic Treatment Central Antiemetic Agents Dopamine D2 Receptor Antagonists Benzimidazole Derivatives Phenothiazines and Butyrophenones Antihistamines and Antimuscarinic Agents Serotonin Antagonists Glucocorticoids Cannabinoids Neurokinin-1 Receptor Antagonists Adjuvant Agents and Therapies Gastric Prokinetic Agents Serotonin 5-HT4 Receptor Agonists Motilin Receptor Agonists Gastric Electrical Stimulation Acknowledgment Chapter 16: Diarrhea Definition Pathophysiology Osmotic Diarrhea Secretory Diarrhea Complex Diarrhea Clinical Classification Acute Versus Chronic Diarrhea Large-Volume Versus Small-Volume Diarrhea Osmotic Versus Secretory Diarrhea Watery Versus Fatty Versus Inflammatory Diarrhea Epidemiologic Features Differential Diagnosis Evaluation History Physical Examination Acute Diarrhea Chronic Diarrhea Chronic Secretory Diarrhea Chronic Osmotic Diarrhea Chronic Inflammatory Diarrhea Chronic Fatty Diarrhea Treatment Acute Diarrhea Chronic Diarrhea Selected Diarrheal Syndromes IBS and Functional Diarrhea Food-Induced Diarrhea Microscopic Colitis Postsurgical Diarrhea Gastric Surgery Bowel Resection Ileostomy Bile Acid–Induced Diarrhea Diarrhea in Hospitalized Patients Factitious Diarrhea Idiopathic Secretory Diarrhea Diarrhea of Obscure Origin Chapter 17: Intestinal Gas Composition and Volume of Gastrointestinal gas Gas Metabolism and Excretion Diffusion of Gas Between the Intestinal Lumen and Blood Mouth to Stomach Small Intestine Colon Colonic Endoluminal Microenvironment and Gas Metabolism Plasticity of Microbiota and Gas Metabolism Odoriferous Gases Anal Evacuation Intestinal Propulsion, Accommodation, and Tolerance to Gas Clinical Gas Problems Repetitive Eructation Pathophysiology Treatment Flatulence Pathophysiology Treatment Impaired Gas Evacuation Abdominal Bloating and Distention Pathophysiology Treatment Nonpharmacologic Therapies Pharmacologic Therapies Pneumatosis Cystoides Intestinalis Chapter 18: Fecal Incontinence Epidemiology Pathophysiology Functional Anatomy and Physiology of the Anorectum Pathogenic Mechanisms Abnormal Anorectal and Pelvic Floor Structures Anal Sphincter Muscles Puborectalis Muscle Nervous System Rectum Abnormal Anorectal and Pelvic Floor Function Impaired Anorectal Sensation Dyssynergic Defecation and Incomplete Stool Evacuation Descending Perineum Syndrome Altered Stool Characteristics Miscellaneous Mechanisms Evaluation History Physical Examination Diagnostic Testing Anorectal Manometry Rectal Sensory Testing Imaging the Anal Canal Anal Endosonography MRI Defecography Balloon Expulsion Test Neurophysiologic Testing Clinical Utility of Tests for Fecal Incontinence Treatment Supportive Measures Specific Therapies Pharmacologic Therapy Biofeedback Plugs, Sphincter Bulking Agents, and Electrical Stimulation Surgery Other Procedures Colostomy Sacral Nerve Stimulation Percutaneous Tibial Nerve Stimulation Novel Therapies Specific Subgroups of Patients Patients with Spinal Cord Injury Patients with Fecal Seepage Older Persons Children Acknowledgment Chapter 19: Constipation Definition and Presenting Symptoms Epidemiology Prevalence Incidence Public Health Perspective Risk Factors Gender Age Ethnicity and Nationality Socioeconomic Status and Education Level Diet and Physical Activity Medication Use Colonic Function Luminal Contents Absorption of Water and Sodium Diameter and Length Motor Function Innervation and the Interstitial Cells of Cajal Defecatory Function Size and Consistency of Stool Classification Pathophysiology Normal-Transit Constipation Slow-Transit Constipation Defecatory Disorders Causes Disorders of the Anorectum and Pelvic Floor Rectocele Descending Perineum Syndrome Diminished Rectal Sensation Rectal Prolapse and Solitary Rectal Ulcer Syndrome Systemic Disorders Hypothyroidism Diabetes Mellitus Hypercalcemia Nervous System Disease Loss of Conscious Control Parkinson Disease Multiple Sclerosis Spinal Cord Lesions Lesions Above the Sacral Segments Lesions of the Sacral Cord, Conus Medullaris, Cauda Equina, and Nervi Erigentes (S2 to S4) Structural Disorders of the Colon, Rectum, and Anus Obstruction Disorders of Smooth Muscle Myopathy Affecting Colonic Muscle Hereditary Internal Anal Sphincter Myopathy Systemic Sclerosis Muscular Dystrophies Disorders of Enteric Nerves Congenital Aganglionosis or Hypoganglionosis Congenital Hyperganglionosis (Intestinal Neuronal Dysplasia) Acquired Neuropathies Neuropathies of Unknown Cause Medications Psychological Disorders Depression Eating Disorders Denied Bowel Movements Fecal Impaction Clinical Assessment History Physical Examination Diagnostic Tests Tests for Systemic Disease Tests for Structural Disease Physiologic Measurements Colonic Transit Time Radiopaque Markers Wireless Motility Capsule Colonic Transit Scintigraphy Tests to Assess the Physiology of Defecation Defecography Balloon Expulsion Test Anorectal Manometry EMG of Striated Muscle Activity Rectal Sensitivity and Sensation Testing Treatment General Measures Reassurance Lifestyle Changes Psychological Support Fluid Intake Dietary Changes and Fiber Supplementation Low-FODMAP Diet Specific Therapeutic Agents Methylcellulose Ispaghula (Psyllium) Calcium Polycarbophil Guar Gum Flaxseed Mixed Soluble and Insoluble Fiber Other Laxatives Osmotic Laxatives Poorly Absorbed Ions Poorly Absorbed Sugars Lactulose Sorbitol and Mannitol Polyethylene Glycol Stimulant Laxatives Anthraquinones Castor Oil Diphenylmethane Derivatives Stool Softeners and Emollients Docusate Sodium Mineral Oils Enemas and Suppositories Phosphate Enemas Saline, Tap Water, and Soapsuds Enemas Stimulant Suppositories and Enemas Prosecretory Laxatives Chloride Channel Activator Guanylate Cyclase C Agonists Linaclotide Plecanatide Serotonergic Laxatives Tegaserod Prucalopride Other Agents Cholinergic Agents Botulinum Toxin Future Agents Chenodeoxycholate Elobixibat Relamorelin Velusetrag Other Forms of Therapy Defecation Training Anorectal Biofeedback Complementary and Alternative Medical Therapies Sacral Nerve Stimulation Surgery Colectomy Selection of Patients Type of Operation Construction of a Stoma Operations for Defecatory Disorders Chapter 20: Gastrointestinal Bleeding Initial Assessment and Management of Acute Gastrointestinal Bleeding History Physical Examination Laboratory Studies Clinical Determination of the Bleeding Site Hospitalization Resuscitation Initial Medical Therapy Endoscopy Endoscopic Hemostasis Imaging Surgery Upper Gastrointestinal Bleeding Epidemiology Risk Factors and Risk Stratification Upper Endoscopic Technique Peptic Ulcer Pathogenesis Histopathology Endoscopic Risk Stratification Doppler Endoscopic Probe Endoscopic Hemostasis Active Bleeding and Nonbleeding Visible Vessels Adherent Clots Clean-Based Ulcers Techniques for Endoscopic Hemostasis Active Arterial Bleeding Nonbleeding Visible Vessel Adherent Clot Oozing of Blood From an Ulcer Without Other Stigmata Flat Spots Clean-Based Ulcers Newer Endoscopic Techniques Hemospray Over-the-Scope Hemoclip Testing for Hp Infection Pharmacologic Therapy Acid Suppression Medication Somatostatin and Octreotide Second-Look Endoscopy Rebleeding After Endoscopic Treatment Angiography, Surgery, and Over-the-Scope Hemoclips Immediate Postendoscopic Management High-Risk Endoscopic Stigmata Intermediate-Risk Stigmata Low-Risk Endoscopic Stigmata Prevention of Recurrent Ulcer Bleeding Hp Infection Aspirin, Other NSAIDs, and Antiplatelet Drugs Repeat Endoscopy to Confirm Gastric Ulcer Healing Other Nonvariceal Causes Esophagitis Ulcer Hemorrhage in Hospitalized Patients Dieulafoy Lesion Mallory-Weiss Tears Cameron Lesions UGI Malignancy GAVE Portal Hypertensive Gastropathy Hemobilia Hemosuccus Pancreaticus Postsphincterotomy Bleeding Aortoenteric Fistula Varices Medical Management of Acute Variceal Bleeding Balloon Tamponade Endoscopic Sclerotherapy Endoscopic Band Ligation TIPS Portosystemic Shunt Surgery Lower Gastrointestinal Bleeding Risk Factors and Risk Stratification Mortality Diagnostic and Therapeutic Approach Anoscopy Flexible Sigmoidoscopy Radionuclide Imaging Angiography CT and CT Colonography Colonoscopy Barium Enema Role of Surgery Causes and Management Diverticulosis Endoscopic Stigmata Endoscopic Hemostasis Angiography and Surgery Colitis Postpolypectomy Bleeding Colon Neoplasia Radiation Proctitis Colonic Angioectasia Internal Hemorrhoids Anal Fissures Rectal Varices Rectal Dieulafoy Lesions Rectal Ulcers Obscure Overt Gastrointestinal Bleeding Causes Angioectasia HHT Blue Rubber Bleb Nevus Syndrome Meckel Diverticulum NSAID–Induced Small Intestinal Erosions and Ulcers Small Intestinal Neoplasms Small Intestinal Diverticula Dieulafoy Lesion of the Small Intestine Diagnostic Tests Imaging Endoscopy Push Enteroscopy Intraoperative Endoscopy and Surgical Exploration Capsule Endoscopy Deep Enteroscopy of the Jejunum and Ileum Overall Approach Obscure Occult Gastrointestinal Bleeding and Iron Deficiency Anemia Fecal Occult Blood Iron Deficiency Anemia Chapter 21: Jaundice Bilirubin Metabolism and Measurement Metabolism Measurement Differential Diagnosis of Hyperbilirubinemia Disorders of Bilirubin Metabolism Isolated Unconjugated Hyperbilirubinemia Increased Bilirubin Production Decreased Bilirubin Uptake by Hepatocytes Decreased Hepatocellular Bilirubin Conjugation Isolated Conjugated or Mixed Hyperbilirubinemia Liver Disease Acute or Subacute Hepatocellular Injury Chronic Hepatocellular Disease Hepatic Disorders with Prominent Cholestasis Infiltrative Diseases Disorders Involving Cholangiocyte Injury Cholestasis with Minimal Histologic Abnormalities Atypical Presentations of Cholestasis Jaundice in Pregnancy Jaundice in the Critically Ill Patient Bile Duct Obstruction Choledocholithiasis Bile Duct Diseases Extrinsic Compression Diagnostic Approach to Jaundice History and Physical Examination Initial Laboratory Studies Overall Approach Imaging Studies Abdominal US CT MRCP ERCP Percutaneous Transhepatic Cholangiography EUS Nuclear Imaging Studies Suggested Strategies for Imaging Other Studies Serologic Testing Liver Biopsy Therapeutic Approaches Obstructive Jaundice Nonobstructive Jaundice Chapter 22: Biopsychosocial Issues in Gastroenterology Conceptualization of Gastrointestinal Illness Biomedical Model Biopsychosocial Model Early Life Learning Developmental Aspects Physiologic Conditioning Culture, Family, and Society Psychosocial Environment Life Stress and Abuse Psychological Factors Personality Psychiatric Diagnosis Psychological Distress Coping and Social Support Brain-Gut Axis Stress and GI Function Definition of Stress Effects of Stress on GI Function Role of Neurotransmitters Hypothalamic-Pituitary-Adrenal Axis Regulation of Visceral Pain Amplification of Visceral Signals Transmission to the CNS Central Amplification Stress-Mediated Effects Spinal Cord Activation of Glia Structural Changes Descending Modulation Cytokines and the Brain Symptom Experience and Behavior Clinical Applications History Taking Evaluating the Data Diagnostic Decision Making Treatment Approach Establishing a Therapeutic Relationship Eliciting, Evaluating, and Communicating the Role of Psychosocial Factors Providing Reassurance Recognizing the Patient’s Adaptations to Chronic Illness Reinforcing Healthy Behaviors Psychopharmacologic Treatment Tricyclic Antidepressants Selective Serotonin Reuptake Inhibitors Serotonin and Norepinephrine Reuptake Inhibitors Tetracyclic Agents Anti-Anxiety Agents Atypical Antipsychotic Agents Opioids Augmentation Treatment Prevention of Relapse Pharmacogenomic Testing Behavioral Treatments Clinician-Related Issues Chapter 23: Factitious Gastrointestinal Disease Factitious Disorder, Subtle Form Etiology and Motives Risk of Iatrogenic Disease Diagnosis and Detection Management Ethical Issues Related to Privacy and Confidentiality Legal Issues Related Abnormal Illness Behaviors Somatic Symptom Disorder Malingering Factitious Behavior in Patients With Bulimia Special Issues Related to Gastroenterology Surreptitious Laxative Ingestion Factitious Diarrhea Concealed Vomiting Factitious Anemia and Factitious GI Blood Loss Factitious Cancer Lessons From Case Reports Pitfalls in the Diagnosis and Management of Abnormal Illness Behavior Acknowledgment Part IV: Topics Involving Multiple Organs Chapter 24: Oral Diseases and Oral Manifestations of Gastrointestinal and Liver Diseases Lip Disorders Cheilitis Lip Neoplasms Salivary Disorders Xerostomia Sjögren Syndrome Tongue Disorders Glossitis, Glossodynia, and Oral Dysesthesia Hypogeusia and Dysgeusia Geographic Tongue Fissured Tongue Black Hairy Tongue Strawberry Tongue Atrophic Tongue Hypertrophic Tongue Leukoplakia Herpetic Geometric Glossitis Gingival Disorders Gingival Enlargement Gingivostomatitis Acute Necrotizing Ulcerative Gingivitis Lead Poisoning Oral Manifestations of Infections, Neoplasms, and Other Selected Disorders Candidiasis Herpesvirus Infections Human Papillomavirus Infection Kaposi Sarcoma Other HIV-Related Conditions Squamous Cell Carcinoma Inflammatory Bowel Disease Gastroesophageal Reflux (GERD) Liver Disease Recurrent Aphthous Ulcers Behçet Disease Cutaneous Disorders with Oral Manifestations Amyloidosis Nutritional Deficiencies Chapter 25: Cutaneous Manifestations of Gastrointestinal and Liver Diseases Vesiculobullous Skin Diseases Pemphigoid Pemphigus Epidermolysis Bullosa Erythema Multiforme Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Spectrum Lichen Planus Cutaneous Manifestations of Inflammatory Bowel Disease Vascular and Connective Tissue Disorders Cutaneous Manifestations of Gastrointestinal Malignancies Polyposis Syndromes Internal Malignancy and Related Disorders Cutaneous Metastases Cutaneous Manifestations of Liver Disease Drug-Induced Liver Disease in Patients With Skin Disease Parasitic Diseases of the Skin and Gastrointestinal Tract Dermatitis Herpetiformis and Celiac Disease Vitamin and Mineral Deficiencies Chapter 26: Diverticula of the Pharynx, Esophagus, Stomach, and Small Intestine Zenker Diverticula Epidemiology, Etiology, and Pathophysiology Clinical Features and Diagnosis Complications Treatment and Prognosis Diverticula of the Esophageal Body Epidemiology, Etiology, and Pathophysiology Clinical Features and Diagnosis Complications Treatment and Prognosis Esophageal Intramural Pseudodiverticula Epidemiology, Etiology, and Pathophysiology Clinical Features and Diagnosis Complications Treatment and Prognosis Gastric Diverticula Epidemiology, Etiology, and Pathophysiology Clinical Features and Diagnosis Complications Treatment and Prognosis Duodenal Diverticula Extraluminal Diverticula Epidemiology, Etiology, and Pathophysiology Clinical Features and Diagnosis Complications Treatment and Prognosis Intraluminal Diverticula Epidemiology, Etiology, and Pathogenesis Clinical Features and Diagnosis Complications Treatment and Prognosis Jejunal Diverticula Epidemiology, Etiology, and Pathophysiology Treatment and Prognosis Chapter 27: Abdominal Hernias and Gastric Volvulus Diaphragmatic Hernias Hiatal and Paraesophageal Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Congenital Diaphragmatic Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Traumatic and Posttraumatic Diaphragmatic Hernias Etiology and Pathogenesis Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Gastric Volvulus Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Inguinal and Femoral Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Post-Surgery Complications and Recurrence Inguinal Hernias and Colorectal Cancer Screening Inguinal Hernias and Benign Prostatic Hyperplasia Other Ventral Hernias Incisional Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Epigastric and Umbilical Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Spigelian Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Pelvic and Perineal Hernias Etiology and Pathogenesis Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Lumbar Hernias Etiology and Pathophysiology Epidemiology Clinical Features, Diagnosis, and Complications Treatment and Prognosis Internal Hernias Etiology and Pathophysiology Epidemiology Clinical Features and Diagnosis Treatment and Prognosis Chapter 28: Foreign Bodies, Bezoars, and Caustic Ingestions Gastrointestinal Foreign Bodies Epidemiology Pathophysiology History and Physical Examination Diagnosis Imaging Endoscopy Treatment Nonendoscopic Methods Endoscopic Methods Specific Foreign Bodies Food Impaction Sharp and Pointed Objects Long Objects Blunt Objects: Coins, Batteries, and Magnets Narcotic Packets Colorectal Foreign Bodies Procedure-Related Complications Bezoars Epidemiology Clinical Features Diagnosis Treatment Caustic Ingestions Epidemiology Pathophysiology Alkali Acid Clinical Features Diagnosis Treatment Late Complications Chapter 29: Abdominal Abscesses and Gastrointestinal Fistulas Abdominal Abscess Pathophysiology Bacteriology Diagnosis CT US MRI Radiographic Studies Nuclear Medicine Studies Management Stabilization Antibiotic Therapy Source Control and Drainage Percutaneous Abscess Drainage Drainage of Specific Types of Abscesses Subphrenic Abscesses Pelvic Abscesses Appendiceal Abscesses Peridiverticular Abscesses Endoscopic Management Surgical Management Outcomes Gastrointestinal Fistulas Classification Pathophysiology Diagnosis Management Stabilization Establishment of Adequate Drainage Nutritional Support Medical Therapy Somatostatin Analogs Management of Crohn Disease Nonsurgical Intervention Surgical Intervention Outcomes Chapter 30: Eosinophilic Disorders of the Gastrointestinal Tract Eosinophil Biology and Potential Diagnostic and Therapeutic Targets Gastrointestinal Eosinophils in Healthy States Eosinophil-Associated Gastrointestinal Disorders Eosinophilic Esophagitis Etiology Clinical Features and Diagnostic Studies Treatment Prognosis Eosinophilic Gastritis, Enteritis, and Gastroenteritis Etiology Clinical Features and Diagnostic Studies Treatment Prognosis Eosinophilic Colitis Etiology Clinical Features and Diagnostic Studies Treatment Prognosis Resources Chapter 31: Protein-Losing Gastroenteropathy Definition and Normal Physiology Pathophysiology Clinical Features Diseases Associated with Protein-Losing Gastroenteropathy Diseases Without Mucosal Erosions or Ulcerations Ménétrier Disease Hp Gastritis Allergic Gastroenteropathy SLE Diseases with Mucosal Erosions or Ulcerations Diseases with Lymphatic Obstruction or Elevated Lymphatic Pressure Diagnosis Laboratory Tests Approach to the Patient with Suspected ­Protein-Losing Gastroenteropathy Treatment and Prognosis Chapter 32: Gastrointestinal Lymphomas General Principles of Lymphoma Management Diagnosis Staging and Prognostic Assessment Treatment Gastric Lymphomas Gastric Marginal Zone B Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (Lymphomas) Epidemiology Cause and Pathogenesis Hp Infection Evidence for Antigen-Driven B Cell Proliferation Genetic Studies Common Molecular Pathways From Mucosa-Associated Lymphoid Tissue Lymphoma Chromosomal Translocations Model for the Pathogenesis of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Pathology Gross Appearance and Location Histology Immunophenotype Molecular Tests of Monoclonality Clinical features Symptoms, Signs, and Laboratory Tests Diagnosis and Staging Staging System and Prognostic Assessment Treatment Stage I Disease Stage II or IV Disease Diffuse Large B Cell Lymphoma of the Stomach Epidemiology Cause and Pathogenesis Pathology Clinical Features Treatment Uncommon Gastric Lymphomas Small Intestinal Lymphomas Marginal Zone B Cell Lymphoma of Malt Type Diffuse Large B Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Burkitt Lymphoma Immunoproliferative Small Intestinal Disease Epidemiology Cause and Pathogenesis Pathology Clinical Features Diagnosis and Staging Treatment Enteropathy-Associated T Cell Lymphoma Epidemiology Cause and Pathogenesis Pathology Clinical Features Treatment Uncommon Small Intestinal Lymphomas Natural Killer Type T Cell Intestinal Lymphoma Other Gastrointestinal Sites Immunodeficiency-Related Lymphomas Posttransplantation Lymphoproliferative Disorders Iatrogenic Lymphoproliferative Disorders HIV–Associated Non-Hodgkin Lymphoma Chapter 33: Gastrointestinal Stromal Tumors Pathology Molecular Pathogenesis Molecular Pharmacology Epidemiology Clinical Features Esophageal Tumors Gastric Tumors Duodenal and Jejunoileal Tumors Colonic and Anorectal Tumors Diagnosis Imaging EUS CT and MRI PET/CT Somatostatin Receptor Scintigraphy Biopsy Differential Diagnosis Treatment Primary Localized Disease (Early-Stage Disease) Surgery Adjuvant Radiation Therapy Adjuvant Therapy With Imatinib Neoadjuvant Therapy Advanced-Stage Disease Systemic and Locoregional Chemotherapy, Radiotherapy, and Debulking Surgery Imatinib Mesylate Sunitinib Malate Regorafenib Alternative Agents Future Agents Special Considerations Imaging of Clonal Progression Carney Triad and the Carney-Streatakis Dyad Familial Gastrointestinal Stromal Tumors Other Genetic Tumor Syndromes Associated With Gastrointestinal Stromal Tumors Gastrointestinal Stromal Tumors in Children Chapter 34: Neuroendocrine Tumors Historical Aspects Epidemiology Origin and Histochemical Features Classification Molecular Pathogenesis Multiple Endocrine Neoplasia and Other Inherited Syndromes MEN-1 Von Hippel–Lindau Disease Neurofibromatosis-1 Tuberous Sclerosis Functional Tumors Insulinomas Pathophysiology and Pathology Clinical Features Diagnosis Treatment Medical Therapy Surgical Therapy Gastrinomas Pathophysiology and Pathology Clinical Features Diagnosis Treatment Control of Gastric Acid Hypersecretion Treatment of Localized Gastrinoma Glucagonomas Pathophysiology and Pathology Clinical Features Diagnosis Treatment Medical Treatment Surgical Treatment VIPomas Pathophysiology and Pathology Clinical Features Diagnosis Treatment Medical Treatment Surgical Treatment Other Functional Pnets Nonfunctional Pnets Clinical Features Treatment GI-NETs (Carcinoids) Gastric NETs Small Intestinal NETs (Jejunal/Ileal Carcinoid Tumors) Appendiceal NETs (Carcinoids) Rectal NETs (Carcinoids) Duodenal and Ampulla of Vater NETs (Carcinoids) Colonic NETs (Carcinoids) Carcinoid Syndrome Pathophysiology Clinical Features and Diagnosis Treatment Tumor Localization Endoscopy Endoscopic Ultrasonography Computed Tomography and Magnetic Resonance Imaging Somatostatin Receptor Imaging Treatment of Metastatic Disease Cytoreductive Surgery Liver-directed Nonsurgical Therapies Radiofrequency Ablation (RFA) and Other Ablative Methods Hepatic Artery Embolization and Chemoembolization Hepatic Radioembolization Liver Transplantation Somatostatin Analogs Interferon-α Everolimus Sunitinib Peptide Receptor Radionuclide Radiotherapy 177Lutetium-Dotatate Cytotoxic Chemotherapy Treatment of Poorly Differentiated Tumors References Chapter 35: Gastrointestinal Consequences of Infection with Human Immunodeficiency Virus Odynophagia and Dysphagia Diarrhea Abdominal Pain Anorectal Disease Gastrointestinal Bleeding Hepatobiliary Disease References Chapter 36: Gastrointestinal and Hepatic Complications of Solid Organ and Hematopoietic Cell Transplantation Complications of solid organ transplantation Kidney and Kidney/Pancreas Transplantation Liver Transplantation Heart, Lung, and Heart-Lung Transplantation Intestinal Transplantation Problem-Oriented Approach to Diagnosis in Solid Organ Transplantation Recipients Upper Intestinal Symptoms and Signs Diarrhea and Constipation Abdominal Pain Gastrointestinal Bleeding Gastrointestinal Malignancy Hepatobiliary Complications Complications of Hematopoietic Cell Transplantation Evaluation of Intestinal and Liver Disorders Before Hematopoietic Cell Transplantation Ulcers and Tumors in the Intestinal Tract Diarrhea Perianal Pain Fungal Liver Infections Viral Hepatitis in Allogeneic Hematopoietic Cell Transplant Donors Liver Disease in Candidates for Hematopoietic Cell Transplantation Gallbladder and Bile Duct Stones Iron Overload Problems From the Time of the Transplant Through the First Year Nausea, Vomiting, and Anorexia Jaundice, Hepatomegaly, and Abnormal Liver Tests Sinusoidal Obstruction Syndrome Cholestatic Disorders Cholangitis Lenta Acute Graft-Versus-Host Disease Drug-Induced Liver Injury Acute Hepatocellular Injury Fungal and Bacterial Infections Gallbladder and Biliary Disease Malignant Hepatic Disorders Idiopathic Hyperammonemia and Coma GI Bleeding Dysphagia, Painful Swallowing, and Esophageal Pain Diarrhea Conditioning Therapy Graft-Versus-Host Disease Infection Other Causes of Diarrhea Abdominal Pain Perianal Pain Problems in Long-Term Transplant Survivors Esophageal Symptoms Upper Gut Symptoms: Anorexia, Nausea, Vomiting, Satiety Mid-Gut and Colonic Symptoms: Diarrhea and Abdominal Pain Graft-Versus-Host Disease of the Liver Chronic Viral Hepatitis and Cirrhosis Ascites Other Liver Disorders Gallbladder and Biliary Diseases Pancreatic Disease Iron Overload References Chapter 37: Gastrointestinal and Hepatic Manifestations of Systemic Diseases Collagen Vascular and Inflammatory Diseases Rheumatoid Arthritis Hepatic Involvement Drug-Induced Side Effects Adult-Onset Still Disease Systemic Sclerosis Esophageal Involvement Gastric Involvement Small Bowel Involvement Colonic Involvement Anal Involvement Miscellaneous Problems Systemic Lupus Erythematosus Vasculitis Esophageal, Gastric, and Intestinal Involvement Pancreatic and Gallbladder Involvement Ascites and Peritonitis Hepatic Involvement Myopathies Sjögren Syndrome Mixed Connective Tissue Disease Polyarteritis Nodosa Henoch-Schönlein Purpura Eosinophilic Granulomatosis With Polyangiitis Granulomatosis With Polyangiitis Cryoglobulinemia Behçet Disease Spondyloarthropathies Familial Mediterranean Fever Disorders of Connective Tissue IgG4-Related Disease Oncologic and Hematologic Diseases Metastases to the Gastrointestinal Tract Paraneoplastic Syndromes Hematologic Malignancies Liver Involvement in Systemic Lymphomas GI and Liver Involvement in Leukemia Systemic Mastocytosis Myelophthisic and Myeloproliferative Disorders Dysproteinemias Red Blood Cell Dyscrasias Sickle Cell Disease Splenic Involvement Biliary Tract Involvement Hepatic Involvement Miscellaneous GI Problems Diagnosis of GI Involvement Hemosiderosis Coagulation Disorders Endocrine Diseases Diabetes Mellitus Diabetes and Cancer Esophageal Involvement Gastric Involvement Small Bowel Involvement Colonic and Anal Involvement Pancreatic Involvement Gallbladder Involvement Hepatic Involvement Thyroid Disease Hyperthyroidism Hypothyroidism Medullary Carcinoma of the Thyroid Parathyroid Disease Hyperparathyroidism Hypoparathyroidism Adrenal Disease Pituitary Disease Disorders of Lipid Metabolism Renal Diseases Neurologic Diseases Diseases of the Central Nervous System Spinal Cord Injury Extrapyramidal (Movement) Disorders Diseases of the Autonomic Nervous System Disease of the Neuromuscular Junction Muscular Dystrophy Pulmonary Disease Critical Illness Sepsis Cardiovascular Diseases Infiltrative Diseases Amyloidosis Oral, Esophageal, and Gastric Involvement Small and Large Bowel Involvement Hepatic Involvement Diagnosis Treatment and Prognosis Granulomatous Liver Disease Sarcoidosis Gastrointestinal Involvement Hepatic and Splenic Involvement Others References Chapter 38: Vascular Lesions of the Gastrointestinal Tract Primary Vascular Lesions Colonic Angioectasia Pathology Pathogenesis Clinical Features and Associated Conditions Diagnosis and Management Angiodysplasia Dieulafoy Lesion Hemangioma Congenital Arteriovenous Malformation Aneurysms Abdominal Aortic Aneurysm Splanchnic Artery Aneurysms Splenic Artery Aneurysms Celiac Artery Aneurysms Superior Mesenteric Artery Aneurysms Mycotic Aneurysm Paraprosthetic-Enteric and Aortoenteric Fistulas Vascular Lesions Associated With Systemic Disorders or Manifestations Hereditary Hemorrhagic Telangiectasia Blue Rubber Bleb Nevus Syndrome Progressive Systemic Sclerosis (Scleroderma) Klippel-Trénaunay and Parkes Weber Syndromes Radiation-Induced Mucosal Injury GAVE (Watermelon Stomach) and Portal Hypertensive Gastropathy, Enteropathy, and Colopathy GAVE Portal Hypertensive Gastropathy (PHG), Enteropathy and Colopathy Anatomic Abnormalities of the Vasculature Superior Mesenteric Artery (SMA) Syndrome Celiac Axis Compression (Median Arcuate Ligament) Syndrome References Chapter 39: Surgical Peritonitis and Other Diseases of the Peritoneum, Mesentery, Omentum, and Diaphragm Anatomy and Physiology Gross Anatomy Microscopic Anatomy Blood Supply and Innervation Physiology Secondary (Surgical) Peritonitis Causes and Pathogenesis Flora Peritoneal Clearance of Bacteria History and Physical Examination Laboratory Tests and Imaging Diagnosis Treatment Antibiotics Surgical Intervention Prognosis Peritonitis of Other Causes Primary Peritonitis Peritonitis With Continuous Ambulatory Peritoneal Dialysis Tuberculous Peritonitis Peritonitis Associated With AIDS Fitz-Hugh-Curtis Syndrome or Chlamydia Peritonitis Fungal and Parasitic Peritonitis Starch Peritonitis Rare Causes Intra-Abdominal Adhesions Peritoneal Tumors Tumors Metastatic to the Peritoneum Clinical Features General Treatment Surgery and Intraperitoneal Chemotherapy Malignant Bowel Obstruction Therapeutic Paracentesis Pseudomyxoma Peritonei Mesothelioma Pelvic Lipomatosis and Peritoneal Cysts Diseases of the Mesentery and Omentum Hemorrhage Tumors Mesenteric Cysts Solid Tumors Multifocal Leiomyomas (Leiomyomatosis Peritonealis Disseminata) Castleman Disease Inflammatory and Fibrotic Conditions Diagnosis and Treatment Infarction of the Omentum Epiploic Appendagitis Diseases of the Diaphragm Hernias and Eventrations Tumors Hiccups Laparoscopy in the Evaluation of Peritoneal Diseases General Considerations Evaluation of Ascites of Unknown Origin Staging Laparoscopy References Chapter 40: Gastrointestinal and Hepatic Disorders in the Pregnant Patient Gastrointestinal and Hepatic Function in Normal Pregnancy Esophageal Function GI Function Immune Function and the Intestinal Microbiota Gallbladder Function Hepatic Function Drug Safety in Pregnant Patients Endoscopy During Pregnancy Imaging and Radiation Exposure During Pregnancy GI Disorders and Pregnancy Nausea, Vomiting, and Hyperemesis Gravidarum GERD PUD IBD Appendicitis Gallbladder and Pancreatic Disorders and Pregnancy Gallstone Disease Acute Pancreatitis Hepatic Disorders Unique to Pregnancy Cholestasis of Pregnancy Preeclampsia HELLP Syndrome Hepatic Rupture, Hematoma, and Infarct Acute Fatty Liver of Pregnancy Other Hepatic Disorders and Pregnancy Viral Hepatitis HEV HSV HBV and HDV HCV Chronic Liver Disease and Portal Hypertension Wilson Disease Autoimmune Liver Diseases Hepatic Tumors and Mass Lesions Hepatic Vein Thrombosis (Budd-Chiari Syndrome) Pregnancy After Liver Transplantation References Chapter 41: Acute and Chronic Gastrointestinal Side Effects of Radiation Therapy Molecular Mechanisms of Radiation-Induced GI Damage Serial versus parallel organ function Small intestine Incidence and Clinical Features Treatment and Prevention Esophagus Incidence and Clinical Features Treatment and Prevention Stomach Incidence and Clinical Features Treatment and Prevention Colon and rectum Incidence and Clinical Features Treatment and Prevention Anus Incidence and Clinical Features Treatment Pancreas and liver Incidence and Clinical Features Pancreas Liver Treatment Pancreas Liver Therapeutic techniques to reduce toxicity References Chapter 42: Preparation for and Complications of Gastrointestinal Endoscopy Complications of Newer Endoscopic Techniques Preparation of the Patient for Endoscopy History and Physical Examination Antibiotic Prophylaxis Management of Anticoagulant and Antiplatelet Drugs Informed Consent Sedation Infections Electrosurgery Timing and Severity of Complications EGD Cardiopulmonary Events Topical Anesthesia Perforation Endoscopic Hemostasis Enteral Access Procedures Mucosal Ablation and Resection Other Therapeutic Procedures Small Bowel Endoscopy Balloon-Assisted Enteroscopy Capsule Endoscopy Colonoscopy Perforation Bleeding Post-Polypectomy Electrocoagulation Syndrome Complications Related to Colon Preparation Others ERCP Hemorrhage Perforation Cholangitis Pancreatitis EUS Newer Endoscopic Techniques References Part V: Esophagus Chapter 43: Anatomy, Histology, Embryology, and Developmental Anomalies of the Esophagus Anatomy and Histology Musculature Innervation Circulation Mucosa Submucosa Embryology Developmental Anomalies Esophageal Atresia and Tracheoesophageal Fistula Congenital Esophageal Stenosis Esophageal Duplications Vascular Anomalies Esophageal Rings Esophageal Webs Heterotopic Gastric Mucosa (Inlet Patch) References Chapter 44: Esophageal Neuromuscular Function and Motility Disorders Motor and Sensory Function Oropharynx and Upper Esophageal Sphincter The Pharyngeal Swallow Esophagus Esophageal Peristalsis Longitudinal Muscle Esophagogastric Junction (EJG) LES Relaxation Transient LES Relaxations Esophageal Sensation Esophageal Motility Disorders Epidemiology Pathogenesis Oropharyngeal Dysphagia Stroke Amyotrophic Lateral Sclerosis Parkinson Disease Vagus Nerve Disorders Oculopharyngeal Muscular Dystrophy Myasthenia Gravis Hypopharyngeal (Zenker) Diverticula and Cricopharyngeal Bar Achalasia Distal Esophageal Spasm (DES) Hypercontractile (Jackhammer) Esophagus Absent Peristalsis Clinical Features Achalasia Distal Esophageal Spasm Hypercontractile Esophagus Absent Contractility Differential Diagnosis Achalasia Chagas Disease Pseudoachalasia Postsurgical Dysfunction Distal Esophageal Spasm Diagnostic Methods Endoscopy Contrast Imaging High Resolution Manometry (HRM) Intraluminal Impedance Measurement Sensory Testing Treatment Oropharyngeal Dysphagia Identification of the Underlying Disease Disorders Amenable to Surgery Patterns of Oropharyngeal Dysphagia Amenable to Swallow Therapy Evaluating Aspiration Risk Hypopharyngeal (Zenker) Diverticula and Cricopharyngeal Bar Achalasia Pharmacologic Therapy Botulinum Toxin Injection Pneumatic Dilation Heller Myotomy Per Oral Endoscopic Myotomy (POEM) Treatment Failures Risk of Squamous Cell Cancer Diffuse Esophageal Spasm (DES) Hypercontractile (Jackhammer) Esophagus Absent Peristalsis Esophageal Hypersensitivity Pharmacologic Treatments Nonpharmacologic Treatments References Chapter 45: Esophageal Disorders Caused by Medications, Trauma, and Infection Medication-Induced Esophageal Injury Mechanisms Clinical Features and Diagnosis Prevention, Treatment, and Clinical Course Specific Medications Antibiotics Bisphosphonates NSAIDs Other Medications Chemotherapy-Induced Esophagitis Esophageal Injury From Variceal Sclerotherapy Esophageal Injury from Nasogastric and other Nonendoscopic Tubes Esophageal Injury from Penetrating or Blunt Trauma Esophageal Tears and Hematomas Mallory-Weiss Syndrome Boerhaave Syndrome Spontaneous Esophageal Hematoma Esophageal Infections in the Immunocompetent Host Candida albicans HSV CMV HPV Other Infections Trypanosoma cruzi Mycobacterium tuberculosis Treponema pallidum Rare Infections Acute Esophageal Necrosis References Chapter 46: Gastroesophageal Reflux Disease Epidemiology Prevalence of Symptoms and GERD Complications Demographic Risk Factors Environmental Risk Factors Health Care Impact Pathogenesis Antireflux Barriers Mechanisms of Reflux Transient Lower Esophageal Sphincter Relaxations Swallow-Induced Lower Esophageal Sphincter Relaxations Hypotensive Lower Esophageal Sphincter Pressure—Strained-Induced or Free Reflux Hiatal Hernia The Acid Pocket Esophageal Acid Clearance Volume Clearance Salivary and Esophageal Gland Secretions Tissue Resistance Gastric Factors Gastric Acid Secretion Duodenogastric Reflux Delayed Gastric Emptying A New Cytokine-Mediated Mediated Mechanism for Esophageal Injury Clinical Features Classic Symptoms Extraesophageal Manifestations Chest Pain Asthma and Other Pulmonary Disorders Ear, Nose, and Throat Diseases Sleep Disorders Differential Diagnosis Associated Conditions Diagnosis Empirical Trial of Acid Suppression Endoscopy Esophageal Biopsy Esophageal Reflux Testing Barium Esophagogram Esophageal Manometry Clinical Course Nonerosive Disease Erosive Disease Complications Hemorrhage, Ulcers, and Perforation Peptic Esophageal Strictures Barrett’s Esophagus Treatment of Uncomplicated Disease Nonprescription Therapies Lifestyle Modifications Over-the-Counter Medications Prescription Medications Prokinetic Drugs Transient Lower Esophageal Sphincter Relaxation Inhibitors H2RAs PPIs Maintenance Therapies Safety of PPI Therapy Surgical Therapy Novel Endoscopic/Surgical Therapies Treatment of Peptic Esophageal Strictures References Chapter 47: Barrett Esophagus Diagnosis Epidemiology Pathogenesis Molecular Biology of Neoplasia Dysplasia Management Treatment of GERD Aspirin and Other NSAIDs Endoscopic Surveillance for Dysplasia Treatment of Mucosal Neoplasia Endoscopic Therapies Endoscopic Ablative Therapies Endoscopic Mucosal Resection Status of EET for Dysplasia in Barrett Esophagus EET for Nondysplastic Barrett Metaplasia Recommendations References Chapter 48: Esophageal Tumors Carcinomas Esophageal Squamous Cell Carcinoma Esophageal Adenocarcinoma Pathogenesis Clinical Features Diagnosis Screening and Surveillance Staging Endoscopy with Mucosal Biopsies Multidetector CT and 18F-FDG-PET EUS Advanced Techniques Treatment Surgery Techniques Lymph Node Dissection Outcomes Endoscopic Treatment Endoscopic Therapy With Curative Intent Endoscopic Therapy with Palliative Intent Chemotherapy and Radiation Therapy Neoadjuvant Chemotherapy Neoadjuvant Chemoradiotherapy Neoadjuvant Radiation Therapy Adjuvant Chemoradiotherapy Targeted Therapy Immunotherapy Prognosis Other Malignant Epithelial Tumors Squamous Cell Carcinoma Variants Small Cell Carcinoma Malignant Melanoma Benign Epithelial Tumors Squamous Papilloma Adenoma Inflammatory Fibroid Polyp Malignant Nonepithelial Tumors Lymphoma Sarcoma GIST Metastases Benign Nonepithelial Tumors Leiomyoma Granular Cell Tumor Fibrovascular Polyp Hamartoma Hemangioma Lipoma Conflicts of Interest and Acknowledgement References Part VI: Stomach and Duodenum Chapter 49: Anatomy, Histology, and Developmental Anomalies of the Stomach and Duodenum Embryology and Anatomy of the Stomach Vascular Supply and Drainage; Lymphatic Drainage Gastric Innervation Tissue Layers of the Stomach Microscopic Anatomy Embryology and Anatomy of the Duodenum Vascular Supply and Drainage; Lymphatic Drainage Duodenal Innervation Microscopic Anatomy Congenital Anomalies of the Stomach and Duodenum Gastric Atresia Pathogenesis Clinical Features and Diagnosis Treatment Microgastria Clinical Features and Diagnosis Treatment Gastric Diverticulum Clinical Features and Diagnosis Treatment Gastric Duplication Clinical Features and Diagnosis Treatment Gastric Teratoma Clinical Features and Diagnosis Treatment Gastric Volvulus Infantile Hypertrophic Pyloric Stenosis Clinical Features and Diagnosis Treatment Adult Hypertrophic Pyloric Stenosis Clinical Features and Diagnosis Treatment Congenital Absence of the Pylorus Duodenal Atresia and Stenosis Clinical Features and Diagnosis Treatment Annular Pancreas Clinical Features and Diagnosis Treatment Duodenal Duplication Cysts Clinical Features and Diagnosis Treatment Intestinal Malrotation and Midgut Volvulus References Chapter 50: Gastric Neuromuscular Function and Neuromuscular Disorders Electrophysiologic Basis for Normal Gastric Neuromuscular Function Extracellular Slow Waves and Plateau and Action Potentials Intracellular Electrical Recordings From Gastric Smooth Muscle Cells Interstitial Cells of Cajal Nervous System Innervation Gastric Neuromuscular Activity During Fasting Gastric Neuromuscular Activity After a Meal Response to Ingestion of Solid Foods Response to Ingestion of Liquids Regulation of Gastric Neuromuscular Activity After A Meal Gastric Sensory Activities The Stomach and the Regulation of Food Intake, Hunger, and Satiety Developmental Aspects of Gastric Neuromuscular Function Assessment of Gastric Neuromuscular Function Gastric Emptying Rate Scintigraphy Capsule Technology Breath Tests US CT and MRI Gastric Contractions Antroduodenal Manometry Capsule Technology Gastric Myoelectrical Activity Gastric Relaxation, Accommodation, and Volume Barostat Tests Scintigraphy and Other Tests Non-Nutrient Liquid and Nutrient Drink Satiety Tests Pyloric Sphincter Tests Antroduodenal Manometry Histopathologic Studies in Gastric and Pyloric Neuromuscular Disorders Neuromuscular Disorders of the Stomach Gastroparesis Diabetic Gastroparesis Postsurgical Gastroparesis Ischemic Gastroparesis Fixed Pyloric Obstruction Functional Pyloric Obstruction Idiopathic Gastroparesis Gastric Neuromuscular Dysfunction Associated with Other GI Disorders FD GERD Constipation, IBS, and Pseudo-Obstruction Miscellaneous Conditions Dumping Syndrome and Rapid Gastric Emptying Diagnosis of Gastric Neuromuscular Disorders History Physical Examination Standard Tests Noninvasive Tests Treatment Drug Therapy Prokinetic Agents for Corpus and Antrum Prorelaxant Agents for Fundus and Pylorus Antinausea Therapy Electrical Therapy Acustimulation Gastric Electrical Therapies Gastric Electrical Stimulator Gastric Pacing Sequential Neural Electrical Stimulation Endoscopic Therapy Diet Therapy Dietary Counseling Nutraceuticals Other Approaches References Chapter 51: Gastric Secretion Functional Anatomy Paracrine, Hormonal, Neural, and Intracellular Regulation of Gastric Acid Secretion Histamine Gastrin Acetylcholine (ACh) Somatostatin Miscellaneous Peptides Parietal Cell Intracellular Pathways H+K+-ATPase Inhibitors and Blockers PPIs Potassium-Competitive Acid Blockers Integrated Response to a Meal Hp-Induced Perturbations in Acid Secretion Measurement of Gastric Acid Secretion Indications Methods BAO MAO and PAO Sham Feeding–Stimulated Acid Output Meal-Stimulated Acid Output Diseases Associated with Increased Gastric Acid Secretion Pepsinogen Secretion Gastric Lipase Secretion Intrinsic Factor Secretion Bicarbonate Secretion Mucus Secretion Gastric Cancer Biomarkers in Gastric Juice References Chapter 52: Gastritis and Gastropathy Definitions Acute Gastritis Chronic Gastritis Hp Gastritis Epidemiology, Risk Factors, and Transmission Pathogenesis Diagnosis Chronic Atrophic Gastritis (Gastric Atrophy) EMAG AMAG Carditis Other Infectious Gastritides Viral CMV Other Herpesviruses Measles Bacterial Mycobacteria Actinomycosis Syphilis Other Bacteria Fungal Candidiasis Histoplasmosis Mucormycosis Aspergillosis Cryptococcosis Monascus Ruber Parasitic Cryptosporidiosis Giardiasis Strongyloidiasis Anisakidosis Ascariasis Necatoriasis Capillariasis Granulomatous Gastritides Sarcoid Xanthogranulomatous Gastritis Distinctive Gastritides Collagenous Lymphocytic Eosinophilic Gastritis in Inflammatory Bowel Disease Crohn Disease UC Gastritis Cystica Profunda Allergic Gastritis Reactive Gastropathies Medications, Toxins, and Illicit Drugs Bile Reflux Stress Radiation Graft-Versus-Host Disease Ischemia Prolapse Hyperplastic Gastropathies, Including Ménétrier’s Disease Portal Hypertensive Gastropathy Differential Diagnosis Treatment Hp Infection Primary Treatments Rescue Treatments Prevention of Hp Infection Other Types of Gastritis and Gastropathy References Chapter 53: Peptic Ulcer Disease Epidemiology Etiology and Pathogenesis Hp Infection Use of Aspirin and Other NSAIDs Other Causes of Ulcers and Idiopathic Ulcers Clinical Features and Diagnosis Medical Therapy of Active Peptic Ulcer Disease Pharmaceutical Agents Antacids Antisecretory Agents H2RAs PPIs Potassium-Competitive Acid Blocker Mucosal Protective Agents Hp-associated Ulcers NSAID Ulcers H2RAs PPIs Misoprostol Other Causes of Ulcers and Idiopathic Ulcers Refractory Ulcers Prevention of Ulcer Disease Antacids H2RAs Misoprostol PPIs COX-2 Inhibitors (In Place of NSAIDs) Assessing Risk and Choice of Agent(s) Complications and Their Treatment Bleeding Endoscopic Therapy Injection Methods Thermal Methods Mechanical Methods Antisecretory Therapy Surgical Therapy Angiographic Therapy Perforation Medical Therapy Surgical Therapy Obstruction Medical Therapy Endoscopic Therapy Surgical Therapy Stress ulcers References Chapter 54: Adenocarcinoma of the Stomach and Other Gastric Tumors Epidemiology Etiology and Pathogenesis Hp Infection Dietary Risk Factors Cigarette Smoking Alcohol Obesity Genetic Factors Tumor Genetics Premalignant Conditions Chronic Atrophic Gastritis Intestinal Metaplasia and Dysplasia Gastric Polyps Previous Gastrectomy PUD Ménétrier Disease Screening and Surveillance Prevention Eradication of Hp Aspirin and Other NSAIDs, Including COX-2 Inhibitors Statins Antioxidants Other Dietary Factors Clinical Features Diagnosis Endoscopy CT Gastrography Serum Markers Classification and Staging EUS CT and PET Laparoscopy with Peritoneal Lavage Other Imaging Modalities Restaging after Neoadjuvant Treatment Prognosis and Treatment Surgery Endoscopic Mucosal Resection and Submucosal Dissection Chemotherapy Chemoradiation Intraperitoneal Chemotherapy Unresectable Disease Miscellaneous Gastric Tumors References Part VII: Pancreas Chapter 55: Anatomy, Histology, Embryology, and Developmental Anomalies of the Pancreas History of the Pancreas Anatomy Ductal Structures Circulation Lymphatic Drainage Innervation Histology and Ultrastructure Development of the Pancreas Embryonic and Fetal Development Transcription Factors and Extrinsic Signals Reemergence of Embryonic Factors During Pancreatic Injury Developmental Anomalies Annular Pancreas Pancreas Divisum Ectopic Pancreatic Tissue Pancreatic Agenesis Congenital Cysts Pancreaticobiliary Malunion References Chapter 56: Pancreatic Secretion Functional Anatomy Composition of Exocrine Secretions Inorganic Constituents Organic Constituents Functions of the Major Digestive Enzymes Amylase Lipases Proteases Digestive Enzyme Synthesis and Transport Regulation of Protein Synthesis Cellular Regulation of Enzyme Secretion Organ Physiology Interdigestive Secretion Digestive Secretion Feedback Regulation Pancreatic Secretory Function Tests Direct Tests Indirect Tests Lundh Test Meal Measurement of Fecal Fat Measurement of Fecal Chymotrypsin and Elastase 1 References Chapter 57: Genetic Disorders of the Pancreas and Pancreatic Disorders in Childhood Background Definitions and Terminology Models of Pancreatic Biology and Disease Alcohol and Smoking SAPE The Acinus: An Exocrine Pancreas Functional Unit Model Acinar Cell Dysfunction and Disease Trypsin-Dependent Pancreatitis Pathway Trypsin-Dependent Pancreatitis Pathway Protein Misfolding-Dependent Pancreatitis Pathway Acinar Cell Dysfunction/Failure Without Pancreatitis Duct Cell–Related Pancreatitis Mechanisms Overview of Duct Cell Physiology and Duct-Associated Pancreatitis CF Transmembrane Conductance Regulator Gene (CFTR) Variants Calcium-Sensing Receptor Gene (CASR) Variants Genes that Modify Inflammation, Progression to Chronic Pancreatitis and Modifier Phenotypes CLDN2-MORC4 Hypertriglyceridemia-Associated Gene Variants SLC26A9: CF Disease Severity Modifier CF-Related Diabetes Risk Integration of Genetics And Patient Management Pancreatitis in Children Acute Pancreatitis Recurrent Acute Pancreatitis and Chronic Pancreatitis Clinical Management of Mendelian Disorders of the Pancreas Cystic Fibrosis Treatment of Pancreatic Dysfunction Intestinal manifestations Liver and Biliary Manifestations Other Manifestations Nutritional Management Hereditary Pancreatitis Familial Pancreatitis Schwachman-Diamond Syndrome Rare Genetic Syndromes With Pancreatic Pathology Johanson-Blizzard Syndrome Pearson Marrow-Pancreas Syndrome Pancreatic Agenesis Other Rare Syndromes Isolated Enzyme and Other Digestive Enzyme-Associated Defects Familial Metabolic Syndromes Associated with Recurrent Acute and Chronic Pancreatitis Familial Hyperparathyroidism With Hypercalcemia Chylomicronemia Syndromes Acknowledgment References Chapter 58: Acute Pancreatitis Incidence and Burden of Disease Definitions Course of the Disease Pathogenesis and Pathophysiology Predisposing Conditions Obstruction Gallstones Biliary Sludge and Microlithiasis Tumors Other Causes Ethyl Alcohol and Other Toxins Ethyl Alcohol Other Toxins Drugs Metabolic Disorders Hypertriglyceridemia Diabetes Mellitus Hypercalcemia Infections Vascular Disease Trauma Post-ERCP Postoperative State Hereditary and Genetic Disorders Miscellaneous Causes Controversial Causes Pancreas Divisum SOD Clinical Features History Physical Examination Differential Diagnosis Laboratory Diagnosis Pancreatic Enzymes Serum Amylase Level Serum Lipase Level Other Pancreatic Enzyme Levels Standard Blood Tests Diagnostic Imaging Abdominal Plain Film Chest Radiography Abdominal US EUS and ERCP CT MRI Distinguishing Alcoholic From Gallstone Pancreatitis Predictors of Disease Severity Scoring Systems CT Chest Radiography Treatment Initial Management During the First Week Intravenous Fluid and Electrolyte Resuscitation Respiratory Care Cardiovascular Care Metabolic Complications Antibiotics Urgent ERCP Nutrition Other Non-Interventional Treatments Interventional Treatments Cholecystectomy Interventions for Pancreatic Fluid Collections Other Complications GI Bleeding Splenic complications Bowel Compression or Fistula Formation Long-Term Sequelae of Acute Pancreatitis Abdominal Compartment Syndrome Miscellaneous Complications References Chapter 59: Chronic Pancreatitis Epidemiology Pathology Pathophysiology Etiology Alcohol Tobacco Tropical Pancreatitis Genetic Autoimmune Pancreatitis Obstructive Miscellaneous Recurrent or Severe Acute Pancreatitis Asymptomatic Pancreatic Fibrosis Idiopathic Clinical features Abdominal Pain Increased Pressure with Ischemia and Inflammation Alterations in Peripheral and Central Nociceptive Nerves Other Causes of Pain Steatorrhea (Exocrine Pancreatic Insufficiency) Diabetes Mellitus (Pancreatic Endocrine Insufficiency) Physical examination Diagnosis Tests of Pancreatic Function Direct Tests Indirect Tests Serum Trypsinogen Pancreatic Enzymes in Stool Fecal Fat Excretion Tests of Pancreatic Structure (Imaging) Plain Abdominal Radiography Abdominal US CT MRI ERCP EUS Diagnostic strategy Treatment Abdominal Pain Medical Therapy Analgesics Cessation of Alcohol and Tobacco Antioxidants Pancreatic Enzyme Therapy Endoscopic Therapy Pancreatic Duct Sphincterotomy Stent Placement Pancreatic Duct Stone Removal Combined Endoscopic Therapy Surgical Therapy Nerve Blocks and Neurolysis Treatment of Pain Maldigestion and Steatorrhea Diabetes Mellitus Complications Pseudocyst GI Bleeding Pseudoaneurysm Variceal Bleeding From Splenic Vein Thrombosis Bile Duct Obstruction Duodenal Obstruction Pancreatic Fistulas External Fistulas Internal Fistulas Malignancy Dysmotility References Chapter 60: Pancreatic Cancer, Cystic Pancreatic Neoplasms, and Other Nonendocrine Pancreatic Tumors Pancreatic cancer Epidemiology Incidence Populations at Risk Environmental Factors Pathology Molecular Pathology and Genetic Alterations Clinical Features Diagnosis US and CT ERCP EUS MRI PET/CT US- and EUS-Guided Aspiration Cytology Serum Tumor Markers Staging Treatment Surgical Therapy Adjuvant and Neoadjuvant Therapy Palliative Procedures Treatment of Advanced Disease Distant Metastatic Disease Unresectable/Borderline Resectable Non-Metastatic Disease Cystic Tumors of the Pancreas Mucinous Cystic Neoplasms Serous Cystadenomas Intraductal Papillary Mucinous Neoplasms Solid Pseudopapillary Tumors Other Pancreatic Tumors References Chapter 61: Endoscopic Treatment of Pancreatic Disease Acute Pancreatitis Local Complications of Acute Pancreatitis Pseudocysts Transpapillary Drainage Transmural Drainage Walled-off necrosis Recurrent Acute Pancreatitis Chronic Pancreatitis Pancreatic Ductal Endotherapy Pseudocysts Biliary Strictures Refractory Pain Pancreatic Duct Leaks Pancreatic Cancer Pancreatic Cysts References Part VIII: Biliary Tract Chapter 62: Anatomy, Histology, Embryology, Developmental Anomalies, and Pediatric Disorders of the Biliary Tract Embryology of the Liver and Biliary Tract Anatomy and Histology Bile Ducts Gallbladder Developmental Anomalies Extrahepatic Ducts Gallbladder Approach to Disorders of the Biliary Tract in Infants and Children General Features Diagnosis Pediatric Disorders of the Bile Ducts Biliary Atresia Epidemiology Etiology and Pathogenesis Pathology Clinical Features Treatment Prognosis Spontaneous Perforation of the Bile Duct Bile Plug Syndrome Choledochal Malformations Epidemiology and Classification Etiology Pathology Clinical Features Diagnosis Treatment Hepatic Fibrocystic Disease Pathology Clinical Features Diagnosis Prognosis and Treatment Nonsyndromic Paucity of the Interlobular Bile Ducts Syndromic Paucity of the Interlobular Bile Ducts (Alagille Syndrome, or Arteriohepatic Dysplasia) Etiology Pathology Pathogenesis Clinical Features Prognosis and Treatment PSC Medical Management of Chronic Cholestasis Pediatric Disorders of the Gallbladder Cholelithiasis Epidemiology Pathogenesis Clinical Features Treatment Calculous Cholecystitis Clinical Features Treatment Acalculous Cholecystitis Acute Hydrops of the Gallbladder Gallbladder Dyskinesia References Chapter 63: Biliary Tract Motor Function and Dysfunction Anatomy and Physiology Functional Gallbladder Disorder Sphincter of Oddi Dysfunction Definition Epidemiology Clinical Features Classification Diagnosis Noninvasive Tests Invasive Tests Sphincter of Oddi Manometry Other ERCP-Based Diagnostic Interventions Treatment Medical Therapy Sphincterotomy Failure of Response to Biliary Sphincterotomy Sphincter of Oddi Dysfunction in Pancreatitis Idiopathic Recurrent Acute Pancreatitis Chronic Pancreatitis References Chapter 64: Bile Secretion and the Enterohepatic Circulation Bile Acid Synthesis and Metabolism The Enterohepatic Circulation Hepatic Bile Acid Transport and Bile Secretion Bile Acid–Independent Bile Flow Cholehepatic Shunt Pathway Hepatic Bile Acid Transport Hepatic Sinusoidal Na+-Dependent Bile Acid Uptake Hepatic Sinusoidal Na+–Independent Bile Acid Uptake Hepatic Sinusoidal Bile Acid Efflux Canalicular Bile Acid Transport Intestinal and Renal Bile Acid Transport Intestinal Bile Acid Transport Renal Bile Acid Transport Molecular Mechanisms Disorders of the Enterohepatic Circulation Bile Acid Synthesis Membrane Transport of Bile Acids and Biliary Lipids Bile Acid Biotransformation (Deconjugation and Dehydroxylation) Bile Acid Circulation Biliary Obstruction and Biliary Fistula Cholecystectomy Ileal Resection Bile Acid-Induced Diarrhea Bile Acid–Based Therapy Bile Acid Replacement Therapy UDCA Bile Acid Receptor Agonists and Antagonists Bile Acid Sequestrants and Transport Inhibitors References Chapter 65: Gallstone Disease Types of Gallstones Epidemiology Risk Factors Age and Gender Diet Pregnancy and Parity Rapid Weight Loss TPN Biliary Sludge Drugs Estrogens Lipid-Lowering Drugs Octreotide Ceftriaxone Lipid Abnormalities Systemic Diseases Obesity and Insulin Resistance Diabetes Mellitus Diseases of the Ileum Spinal Cord Injuries NAFLD Celiac Disease Protective Factors Statins Ascorbic Acid Coffee Composition and Abnormalities of Bile Physical Chemistry of Bile Chemical Composition of Bile Physical States of Biliary Lipids Phase Diagrams and Cholesterol Solubility in Bile Hepatic Secretion of Biliary Lipids Source of Lipids Secreted in Bile Biliary Lipid Secretion Pathophysiology Hepatic Hypersecretion of Biliary Cholesterol Rapid Cholesterol Nucleation and Crystallization Imbalance of Pronucleating and Antinucleating Factors Gallbladder Dysfunction Intestinal Factors Growth of Gallstones Genetics Pigment Stones Black Stones Brown Stones Natural History Asymptomatic Stones Stones in Patients With Diabetes Mellitus Symptomatic Stones Special Patient Populations Diagnosis US EUS Oral Cholecystography Cholescintigraphy ERCP CT and MRI Clinical Disorders Biliary Pain and Chronic Cholecystitis Pathogenesis Clinical Features Diagnosis Differential Diagnosis Treatment Acute Cholecystitis Pathogenesis Pathology Clinical Features Natural History Diagnosis Differential Diagnosis Treatment Choledocholithiasis Etiology Clinical Features Natural History Diagnosis Differential Diagnosis Treatment Cholangitis Etiology and Pathophysiology Clinical Features Diagnosis Treatment Uncommon Complications Emphysematous Cholecystitis Cholecystoenteric Fistula Mirizzi Syndrome Porcelain Gallbladder Acknowledgment References Chapter 66: Treatment of Gallstone Disease Medical Treatment Dissolution Therapy Patient Selection Therapeutic Regimens Efficacy Extracorporeal Shock-Wave Lithotripsy Patient Selection Therapeutic Approach Efficacy Bile Duct Stones Surgical Treatment Open Cholecystectomy Technique Results Laparoscopic Cholecystectomy Technique Rationale for Cholangiography Results Choice of Treatment Indications for Treatment Asymptomatic Gallstones Biliary Pain and Chronic Cholecystitis Patient Selection Evaluation Acute Cholecystitis Acalculous Cholecystitis Emphysematous Cholecystitis Gallstone Pancreatitis Special Problems Gallstone Disease During Pregnancy Gallstone Disease During Childhood Mirizzi Syndrome Gallstone Ileus Incidental Cholecystectomy Choledocholithiasis Choledocholithiasis Known Preoperatively Choledocholithiasis Identified During Cholecystectomy Choledocholithiasis Identified After Cholecystectomy Bile Duct Injury and Stricture Postcholecystectomy Syndrome Choledocholithiasis Cystic Duct Remnant SOD Gallstones, Cholecystectomy, and Cancer Biliary Tract Cancer Colorectal Cancer References Chapter 67: Acalculous Biliary Pain, Acute Acalculous Cholecystitis, Cholesterolosis, Adenomyomatosis, and Gallbladder Polyps Acalculous Biliary Pain Definition and Clinical Features Epidemiology and Pathophysiology Diagnosis and Treatment Stimulated Cholescintigraphy Acute Acalculous Cholecystitis Definition Epidemiology Pathogenesis Clinical Features Diagnosis US CT Hepatobiliary scintigraphy Treatment Surgical Cholecystectomy and Cholecystostomy Percutaneous Cholecystostomy Transpapillary or Transmural Endoscopic Cholecystostomy Cholesterolosis Definition Epidemiology Pathology Gross Appearance Microscopic Appearance Pathogenesis Clinical Features Diagnosis Treatment Adenomyomatosis Definition Epidemiology Pathology Gross Appearance Microscopic Appearance Pathogenesis Clinical Features Diagnosis Treatment Gallbladder Polyps Definition Epidemiology Pathology Cholesterol Polyps Adenomyomas Inflammatory Polyps Adenomas Miscellaneous Polyps Clinical Features and Diagnosis Natural History Treatment References Chapter 68: Primary and Secondary Sclerosing Cholangitis Primary Sclerosing Cholangitis Epidemiology Etiology and Pathogenesis Genetic Factors Immunologic Factors Lymphocyte Trafficking Dysbiosis Toxic Bile Theory Biliary Epithelial Cells Infectious and Antigenic Factors Clinical, Laboratory, and Imaging Features PSC and IBD Symptoms Physical Examination Laboratory Findings Imaging Histology Diagnosis Differential Diagnosis Natural History and Prognostic Models Asymptomatic PSC Symptomatic PSC Overall Prognosis Small-Duct PSC PSC in Children Prognostic Models Complications Cholestasis Biliary Stones Cholangiocarcinoma Colonic Neoplasia Peristomal Varices Treatment Medical Treatment of the Underlying Disease Medical Treatment of Complications Endoscopic Management Percutaneous Management Surgical Management Biliary Surgery LT Secondary Sclerosing Cholangitis IgG4-Related Sclerosing Cholangitis Recurrent Pyogenic Cholangitis Clinical Features and Diagnosis Treatment Prognosis and Complications Acknowledgments References Chapter 69: Tumors of the Bile Ducts, Gallbladder, and Ampulla Cholangiocarcinoma Epidemiology Etiology Established Risk Factors Possible Risk Factors Pathology Pathogenesis Clinical Features and Diagnosis Intrahepatic Cholangiocarcinoma Perihilar and Distal Cholangiocarcinoma Staging Treatment Surgical Resection and LT Locoregional Therapies Perihilar and Distal Cholangiocarcinoma Chemotherapy, Radiation Therapy, and Targeted Therapy Palliative Treatment Gallbladder Carcinoma Epidemiology Etiology Pathology Pathogenesis Clinical Features and Diagnosis Staging Treatment Ampullary Carcinoma Epidemiology Etiology Pathology Pathogenesis Clinical Features and Diagnosis Staging Treatment Other Tumors of the Biliary Tract Acknowledgment References Chapter 70: Endoscopic and Radiologic Treatment of Biliary Disease Imaging of the Biliary Tract Transabdominal US MRCP and Multidetector CT Cholangiography Diagnostic EUS ERCP EUS-Guided Biliary Drainage Endoscopic Treatment Bile Duct Stones Bile Leaks PSC Benign Biliary Strictures Indeterminate Biliary Strictures Malignant Biliary Strictures Distal Bile Duct Strictures Perihilar Biliary Obstruction SOD Surgically Altered Anatomy Adverse Events Percutaneous Transhepatic Cholangiography Technique Postoperative Biliary Strictures PSC Bile Leaks Bile Duct Injury Bile Duct Stones Malignant Biliary Obstruction Percutaneous Cholecystostomy Tube Placement Combined Percutaneous and Endoscopic Approaches References Part IX: Liver Chapter 71: Embryology, Anatomy, Histology, and Developmental Anomalies of the Liver Embryology Hepatic Stem Cells and Maturational Lineages Vascular Development Anatomy Nerves Lymphatics Histology Organization of Liver Parenchyma Developmental Anomalies Riedel Lobe Abernethy Malformation References Chapter 72: Liver Physiology and Energy Metabolism Liver Cell Types and Organization Parenchymal Cells Hepatocytes Polarity Plasma Membranes Cell Junctions Cytoskeleton Nucleus Transport Between the Nucleus and the Cytoplasm Endoplasmic Reticulum Golgi Complex Lysosomes Mitochondria Peroxisomes Exocytosis and Endocytosis Functional Zonation of Hepatocytes Bile Duct Epithelial Cells Secretory and Absorptive Functions Primary Cilia Sinusoidal Cells Hepatic Sinusoidal Endothelial Cells Role in Liver Regeneration Kupffer Cells Perisinusoidal Cells Hepatic Stellate Cells Pit Cells Integration of the Functions of the Different Cell Types Cell-Matrix Interactions Components of the Extracellular Matrix Regeneration and Apoptosis of Liver Cells Regeneration Hippo-Yap Pathway of Regulation of Hepatocyte Mitosis Growth Factors That Mediate Hepatic Regeneration Gene Expression During Hepatic Regeneration Immediate Early Genes Delayed Early Genes Cell Cycle Genes Integration of Cytokine and Growth Factors in Regeneration Hepatocyte Growth Factor and C-met Programmed Cell Death Expression of Genes Involved in Apoptosis During Liver Regeneration Protein Synthesis and Degradation in the Liver Hepatic Gene Expression Nuclear Receptors Protein Folding Protein Catabolism Hepatic Nutrient Metabolism Carbohydrates Circadian Rhythm of Gluconeogenesis Regulation of Glucose Uptake and Efflux From the Hepatocyte Formation of Glucose-6-Phosphate Conversion of Glucose-6-Phosphate to Glucose Hepatic Metabolism of Galactose and Fructose Glycogen Formation Regulation of Glycolytic-Gluconeogenic Pathways Carbohydrate Metabolism in Cirrhosis Lipids Fatty Acid Synthesis Beta Oxidation of Fatty Acids Mitochondrial Beta Oxidation Peroxisomal Beta Oxidation Lipoproteins Types Apolipoproteins Lysosomal Hydrolysis of TG via Autophagy Lipolytic Enzymes Lipid Transport Proteins Intestinal and Hepatic Lipid Transport Transport of ApoB-Containing Lipoproteins Transport of ApoA-Containing HDL Lipoprotein Receptors LDL Receptor VLDL Receptor Chylomicron Remnant Receptor LDL Scavenger Receptor HDL Receptor Derangement of Lipid Metabolism in Liver Disease References Chapter 73: Liver Chemistry and Function Tests Bilirubin Metabolism Measurement Approach to the Patient with an Elevated Level Aminotransferases Approach to the Patient with an Elevated Level Alkaline phosphatase GGTP 5′-Nucleotidase Approach to the Patient with an Elevated Level Tests of Hepatic Synthetic Function Albumin Prothrombin Time Tests to Detect Hepatic Fibrosis Quantitative Liver Function Tests Indocyanine Green Clearance Galactose Elimination Capacity Caffeine Clearance Lidocaine Metabolite Formation Aminopyrine Breath Test Bile Acids Specific Applications of Liver Biochemical Testing DILI Surgical Candidacy and Organ Allocation References Chapter 74: Overview of Cirrhosis Pathogenesis Diagnosis Natural History Prognosis Treatment Reversal of Fibrosis Acute-on-Chronic Liver Failure Definition Epidemiology Pathophysiology Clinical Features and Prognosis Treatment References Chapter 75: Hemochromatosis Causes Of Iron Overload Pathophysiology Intestinal Iron Absorption Hepcidin HFE Protein Iron-Induced Tissue Injury and Fibrosis Clinical Features Diagnosis Treatment Prognosis Family Screening References Chapter 76: Wilson Disease Copper Metabolism Molecular Pathogenesis Pathology Clinical Features Hepatic Presentation Neurologic Presentation Psychiatric Presentation Ocular Signs Involvement of Other Systems Diagnosis Tests Approach Mutation Analysis Diagnosis of First-Degree Relatives Treatment Prognosis References Chapter 77: Other Inherited Metabolic Disorders of the Liver Clinical Features of Metabolic Liver Disease α1-Antitrypsin Deficiency Pathophysiology Clinical Features Histopathology Diagnosis Treatment Glycogen Storage Diseases Type I Clinical Features Hepatic Involvement Diagnosis Treatment Type III Clinical Features Treatment Type IV Congenital Disorders of Glycosylation Porphyrias Pathophysiology Acute Porphyrias Cutaneous Porphyrias Hepatic Involvement Diagnosis Treatment Tyrosinemia Pathophysiology Clinical and Pathologic Features Diagnosis Treatment Urea Cycle Defects Pathophysiology Clinical Features Diagnosis Treatment Arginase Deficiency Bile Acid Synthesis and Transport Defects Bile Acid Synthesis Defects Diagnosis Disorders of Enzymes Involved in Modification of the Steroid Ring Disorders of Enzymes Involved in Side-Chain Modification Peroxisomal Disorders Bile Acid Transport Defects Treatment Cystic Fibrosis Clinical and Pathologic Features Pathophysiology Diagnosis Treatment Mitochondrial Liver Diseases References Chapter 78: Hepatitis A Virology Epidemiology Pathogenesis Clinical Features ALF Caused by HAV Infection Extrahepatic Manifestations Autoimmune Hepatitis after Acute Hepatitis A Diagnosis Prevention and Treatment Immunization Against HAV in Patients with Chronic Illnesses References Chapter 79: Hepatitis B Epidemiology Geographic Distribution and Sources of Infection Infectivity Prevalence Acute Hepatitis B Chronic Hepatitis B Virology Viral Replication Genotypes Mutations Hepatitis B Surface Antigen Precore, Basal Core Promoter, and Core HBV DNA Polymerase Pathogenesis Natural History Serum ALT as a Surrogate Marker for Disease Activity HBV DNA Level and Long-Term Complications Clinical and Pathologic Features Acute Hepatitis B Chronic Hepatitis B Extrahepatic Manifestations Arthritis-Dermatitis Polyarteritis Nodosa Glomerulonephritis Cryoglobulinemia Histopathologic Features Acute Flares and Reactivation Spontaneous Flares Immunosuppressive Therapy–Induced Flares Antiviral Therapy–Induced Flares During Interferon Therapy During Nucleos(t)ide Analog Therapy After Withdrawal of a Nucleos(t)ide Analog During Other Antiviral Therapy Flares Associated with Genotypic Variation Flares Caused by Infection With Other Viruses Diagnosis Treatment Goals Barriers Indications HBV DNA ALT Liver Fibrosis Timing Drugs Nucleoside and Nucleotide Analogs Lamivudine Adefovir Dipivoxil Emtricitabine Entecavir Telbivudine Tenofovir Disoproxil Fumarate Tenofovir Alafenamide Treatment Response and Endpoints Monitoring Duration of Therapy Durability of Response Antiviral Resistance Testing Clinical Outcomes Lamivudine Resistance Entecavir Resistance Tenofovir Resistance Multidrug Resistance Interferon-alpha (IFN-a) HBeAg-Positive Chronic Hepatitis B HBeAg-negative Chronic Hepatitis B Treatment Endpoints and Durability Predictors of Response and Stopping Rules Peginterferon Plus Nucleos(t)ide Analogs Nucleos(t)ide Analog Combinations Special Populations Pregnant Women Severe Acute Hepatitis Cirrhosis HBV-HIV Coinfection HBV-HCV Coinfection HBV-HDV Coinfection HBV Reactivation During Immunosuppressive Therapy Screening Risk Stratification Antiviral Prophylaxis Timing and Duration of Prophylaxis Deferred Therapy Future Treatments Entry Inhibitors cccDNA Silencing Small Interfering RNA Core Protein Assembly Modulators HBsAg Release Inhibitors Immune Modulation Prevention Hepatitis B Immune Globulin Hepatitis B Vaccine Vaccination Schedule Postexposure and Perinatal Prophylaxis Bivalent Vaccine Recommendations HBsAg-Positive Health Care Workers Acknowledgment References Chapter 80: Hepatitis C Virology Structure Genomic Organization Viral Replication and Life Cycle Virus Protein Function Genotypes and Quasispecies Epidemiology Incidence and Prevalence Transmission Percutaneous Transmission Nonpercutaneous Transmission Sporadic HCV Infection Pathogenesis Viral Mechanisms Immune-Mediated Mechanisms Clinical features Acute Hepatitis C Chronic Hepatitis C Extrahepatic Manifestations Diagnosis Indirect Assays Direct Assays HCV Genotype Selection of Serologic and Virologic Tests Liver Biopsy and Noninvasive Assessment of Fibrosis Natural History Factors Associated with Progression HCC Treatment Goals Indications and Contraindications Virologic Response Drugs Interferon Ribavirin DAAs NS3/4A Protease Inhibitors (-previrs) NS5A Inhibitors (-asvirs) NS5B Polymerase Inhibitors (-buvirs) Approved DAAs in Common Use Sofosbuvir Sofosbuvir/Ledipasvir Elbasvir/Grazoprevir Sofosbuvir/Velpatasvir Sofosbuvir/Velpatasvir/Voxilaprevir Glecaprevir/Pibrentasvir Acute Hepatitis C Chronic Hepatitis C Genotype 1 Treatment-Naïve Genotype 1a Sofosbuvir/Ledipasvir Noncirrhotic and Compensated Cirrhotic Patients Elbasvir/Grazoprevir Noncirrhotic and Compensated Cirrhotic Patients Without Baseline NS5A RAS Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Treatment-Naïve Genotype 1b Sofosbuvir/Ledipasvir Noncirrhotic and Compensated Cirrhotic Patients Elbasvir/Grazoprevir Noncirrhotic and Compensated Cirrhotic Patients Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients PegIFN/RBV Treatment-Experienced Genotype 1a Sofosbuvir/Ledipasvir Noncirrhotic Patients Elbasvir/Grazoprevir Noncirrhotic and Compensated Cirrhotic Patients without Baseline NS5A RAS Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Alternative IFN-Free DAA Regimens PegIFN/RBV Treatment-Experienced Genotype 1b Sofosbuvir/Ledipasvir Noncirrhotic Patients Elbasvir/Grazoprevir Noncirrhotic and Compensated Cirrhotic Patients Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Alternative IFN-Free DAA Regimens NS3/4A Protease Inhibitor Plus PegIFN/RBV Treatment-Experienced Genotype 1 Sofosbuvir/Ledipasvir Noncirrhotic Patients Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic and Compensated Cirrhotic Patients Alternative IFN-Free DAA Regimens Sofosbuvir (without an NS5A Inhibitor) Treatment-Experienced Genotype 1 Sofosbuvir/Velpatasvir/Voxilaprevir Glecaprevir/Pibrentasvir Sofosbuvir/Velpatasvir Alternative IFN-Free DAA Regimen NS5A Inhibitor Treatment-Experienced Sofosbuvir/Velpatasvir/Voxilaprevir Alternative IFN-Free DAA Regimen Genotype 2 Treatment-Naïve Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients PegIFN/RBV Treatment-Experienced Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Sofosbuvir Treatment-Experienced Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir NS5A Inhibitor Treatment-Experienced Sofosbuvir/Velpatasvir/Voxilaprevir Genotype 3 Treatment-Naïve Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Alternative IFN-Free DAA Regimens PegIFN/RBV Treatment-Experienced Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Sofosbuvir/Velpatasvir/Voxilaprevir Alternative IFN-Free DAA Regimens DAA Treatment-Experienced, Excluding NS5A Inhibitors Sofosbuvir/Velpatasvir/Voxilaprevir ± Ribavirin Glecaprevir/pibrentasvir NS5A Inhibitor DAA Treatment-Experienced Patients Sofosbuvir/Velpatasvir/Voxilaprevir ± Ribavirin Genotype 4 Treatment-Naïve Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Sofosbuvir/Ledipasvir Noncirrhotic and Compensated Cirrhotic Patients Elbasvir/Grazoprevir Noncirrhotic and Compensated Cirrhotic Patients PegIFN/RBV Treatment-Experienced Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Elbasvir/Grazoprevir Sofosbuvir/Ledipasvir Alternative IFN-Free DAA Regimens DAA Treatment-Experienced Sofosbuvir/Velpatasvir/Voxilaprevir Genotype 5 Treatment-Naïve Glecaprevir/Pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Sofosbuvir/Ledipasvir Noncirrhotic and Compensated Cirrhotic Patients PegIFN/RBV Treatment-Experienced Glecaprevir/Pibrentasvir Sofosbuvir/Ledipasvir Sofosbuvir/Velpatasvir DAA Treatment-Experienced Sofosbuvir/Velpatasvir/Voxilaprevir Genotype 6 Treatment-Naïve Glecaprevir/pibrentasvir Noncirrhotic Patients Compensated Cirrhotic Patients Sofosbuvir/Velpatasvir Noncirrhotic and Compensated Cirrhotic Patients Sofosbuvir/Ledipasvir Noncirrhotic and Compensated Cirrhotic Patients PegIFN/RBV Treatment-Experienced Glecaprevir/Pibrentasvir Sofosbuvir/Ledipasvir Sofosbuvir/Velpatasvir DAA Treatment-Experienced Sofosbuvir/Velpatasvir/Voxilaprevir Monitoring and Safety Monitoring Safety HBV Reactivation During DAA Therapy Special Populations HCV-HIV Coinfection Decompensated Cirrhosis HCV Genotypes 1, 4, 5, and 6 Sofosbuvir/Ledipasvir with or without Low-Dose Ribavirin Prior DAA Treatment-experienced Patients DAA treatment-experienced Sofosbuvir/Velpatasvir with or without Weight-Based Ribavirin DAA treatment-experienced patients HCV Recurrence Following LT HCV Genotypes 1, 4, 5, and 6 Sofosbuvir/Ledipasvir ± RBV HCV Genotypes 1 through 6 Glecaprevir/Pibrentasvir Sofosbuvir/Velpatasvir with or withou RBV Sofosbuvir/Velpatasvir/Voxilaprevir Chronic Kidney Disease (CKD) Stage 1, 2, 3, 4, or 5 CKD Pregnancy Acknowledgment References Chapter 81: Hepatitis D Epidemiology Modes of Transmission Virology Structure Life Cycle Genotypes Pathogenesis Diagnosis HDV Antigen Antibody to HDV HDV RNA Clinical Features Natural History Acute HDV Infection Chronic HDV Infection Treatment Acute Hepatitis D Chronic Hepatitis D Interferon-α/Peginterferon-α Combination Peginterferon-α and Nucleos(t)ide Analogs Nucleos(t)ide Analogs LT Novel Therapies Entry Inhibitors Inhibitors of Viral Assembly Inhibitors of Viral Release Prevention References Chapter 82: Hepatitis E Virology Epidemiology Areas of High Endemicity Areas of Lower Endemicity Pathogenesis Clinical features Acute Hepatitis E Extrahepatic Manifestations Chronic Hepatitis E Diagnosis Treatment Prevention Acknowledgment References Chapter 83: Hepatitis Caused by Other Viruses Discovery of Novel Hepatitis Viruses GBV-C/human Pegivirus TT Virus Infection Virology Epidemiology Clinical Features Treatment Sanban, Yonban, AND Sen virus and TT Virus–Like Minivirus Infections The Search for Other Non–A-E Viral Hepatitis Infections Systemic Viral Infections That May Involve the Liver EBV CMV HSV VZV Others References Chapter 84: Bacterial, Parasitic, and Fungal Infections of the Liver, Including Liver Abscesses Bacterial Infections Involving or Affecting the Liver Gram-Positive and Gram-Negative Bacteria Toxic Shock Syndrome: Staphylococcus Aureus or Group A Streptococci Clostridium perfringens Actinomyces Listeria Shigella and Salmonella Yersinia Gonococci Legionella Burkholderia pseudomallei (Melioidosis) Brucella Coxiella burnetii (Q Fever) Bartonellosis (Oroya Fever, Cat-Scratch Fever, and Bacillary Angiomatosis) Bacterial Sepsis and Jaundice Chlamydia Fitz-Hugh–Curtis Syndrome Rickettsiae Rocky Mountain Spotted Fever Ehrlichiae Spirochetes Leptospirosis Syphilis Secondary Syphilis Tertiary (Late) Syphilis Lyme Disease Mycobacteria Parasites Protozoa Malaria The Plasmodium Life Cycle Histopathologic Features Clinical Features Diagnosis Treatment Hyperreactive Malarial Splenomegaly (Tropical Splenomegaly Syndrome) Babesiosis Leishmaniasis Histopathologic Features Clinical Features Diagnosis Treatment Toxoplasmosis Clinical Features Diagnosis Treatment Helminths Nematodes (Roundworms) Toxocariasis Clinical Features Diagnosis Treatment Hepatic Capillariasis Clinical Features Diagnosis Treatment Ascariasis Clinical Features Diagnosis Treatment Strongyloidiasis Clinical Features Diagnosis Treatment Trichinosis Clinical Features Diagnosis Treatment Trematodes (Flukes) Schistosomiasis (Bilharziasis) The Schistosomal Life Cycle Clinical Features Diagnosis Treatment Fascioliasis Clinical Features Diagnosis Treatment Clonorchiasis and Opisthorchiasis Clinical Features Diagnosis Treatment Cestodes (Tapeworms) Echinococcosis The Echinococcal Life Cycle Clinical Features Diagnosis Treatment Fungi Candidiasis Histoplasmosis Liver Abscess Pyogenic Pathogenesis Microbiology Clinical Features Diagnosis Prevention and Treatment Amebic Pathogenesis Clinical Features Diagnosis Treatment References Chapter 85: Vascular Diseases of the Liver Budd-Chiari Syndrome Epidemiology Etiology Pathogenesis Clinical Features Diagnosis and Natural History Treatment Extrahepatic Portal Vein Obstruction Acute Portal Vein Thrombosis in the Absence of Cirrhosis Etiology Pathogenesis Clinical Features Diagnosis and Natural History Treatment Portal Cavernoma Portal Vein Thrombosis in Patients With Cirrhosis Idiopathic Noncirrhotic Portal Hypertension Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease) Etiology Pathology Clinical Features and Diagnosis Treatment Congenital Portosystemic Shunts Ischemic Hepatitis Etiology Clinical Features and Diagnosis Treatment Congestive Hepatopathy Ischemic Cholangiopathy Idiopathic Sinusoidal Dilatation and Peliosis Hepatis Hepatic Artery Aneurysm and Hepatic Infarction Hereditary Hemorrhagic Telangiectasia Diabetic Hepatosclerosis References Chapter 86: Alcohol-Associated Liver Disease Epidemiology Spectrum of Disease Pathogenesis Ethanol Metabolism and Toxic Metabolites Other Metabolic Mechanisms Oxidative Stress Mitochondrial Dysfunction Abnormal Metabolism of Methionine, S-Adenosylmethionine, and Folate Hypoxia Endoplasmic Reticulum Stress, Impaired Proteasome Function, and Autophagy Immune and Inflammatory Mechanisms Gut-Liver Axis and Pathogen-Associated Molecular Patterns (PAMPs) Inflammasome Activation and DAMPs Dysregulated Cytokine Production Immune Responses to Altered Hepatocellular Proteins Genetics and Epigenetic Factors Emerging Mechanisms Fibrosis Diagnosis of Alcohol Abuse Diagnosis of Alcohol-Associated Liver Disease History Physical Examination Laboratory Features Histopathology Conditions That May Resemble ALD NAFLD Hereditary Hemochromatosis DILI Cofactors That May Influence Progression of Alcohol-Associated Liver Disease Prognosis Alcohol-associated Hepatitis Alcohol-associated Cirrhosis Acute-on-Chronic Liver Failure Acute Viral Illness Hepatotoxic Drugs HCC Treatment Abstinence and Lifestyle Modification Nutritional Support Specific Therapy for Alcohol-Associated Hepatitis Glucocorticoids and Pentoxifylline (PTX) Drugs of Unlikely Benefit and Promising New Agents Under Investigation Recommendations Specific Therapy for Alcohol-Associated Cirrhosis LT Optimal Management References Chapter 87: Nonalcoholic Fatty Liver Disease Epidemiology Definitions and Associations Pathogenesis Hepatic Steatosis Steatohepatitis Clinical Features and Diagnosis Liver Biopsy Imaging to Detect Fibrosis Laboratory Tests for Fibrosis Focal Fatty Liver Natural History Clinical Associations Treatment Lifestyle Modification Bariatric Surgery Pharmacotherapy Weight Loss Medications Antioxidants Diabetic Medications Cytoprotective Agents Lipid-Lowering Agents Other Therapies LT References Chapter 88: Liver Disease Caused by Drugs Hepatic Drug Metabolism Role of the Liver in Drug Elimination Pathways of Drug Metabolism Phase 1 and Cytochrome P450 Genetic and Environmental Determinants of Cytochrome P450 Enzymes Developmental Regulation and Constitutive Expression Nutrition and Disease-Related Changes Adaptive Response and Enzyme Induction Inhibition of Drug Metabolism Other Pathways of Drug Oxidation Phase 2 (Conjugation) Phase 3 Effect of Liver Disease on Drug Metabolism Liver Disease Caused by Drugs Definitions and Importance Epidemiology Case Definition: Which Agent Frequencies of Hepatic Drug Reactions Importance of Drugs as a Cause of Liver Disease Risk Factors Genetic Factors Age Gender Concomitant Exposure to Other Agents Previous Drug Reactions Alcohol Nutritional Status Preexisting Liver Disease Other Diseases Pathophysiology Direct Hepatotoxins and Reactive Metabolites Oxidative Stress and the Glutathione System Biochemical Mechanisms of Cellular Injury Types of Cell Death Necrosis Role of Oxidative Stress Role of Hepatic Nonparenchymal Cells and the Innate Immune Response Immunologic Mechanisms Clinicopathologic Features Classification Histopathologic Features Clinical Features DRESS Syndrome Latent Period to Onset Dechallenge and Rechallenge Diagnosis Physician Awareness Exclusion of Other Disorders Extrahepatic Features Chronologic Relationships Which Drug Indications for Liver Biopsy Considerations in Patients with Viral Hepatitis Prevention and Management Dose-Dependent Hepatotoxicity Acetaminophen General Nature, Frequency, and Predisposing Factors Clinical Course, Outcomes, and Prognostic Indicators Treatment Prevention Other Causes Niacin (Nicotinic Acid) Valproic Acid (Sodium Valproate) Antiretroviral Agents Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTIs) Non-nucleoside Reverse Transcriptase Inhibitors Protease Inhibitors Aspirin Others Drug-Induced Acute Hepatitis Immunoallergic Reactions Nitrofurantoin Others Metabolic Idiosyncrasy Isoniazid Other Antituberculosis Drugs Antifungal Drugs Antidiabetic Drugs Thiazolidinediones Other Oral Hypoglycemic Drugs Drugs Used for Psychiatric and Neurologic Disorders Antidepressants Monoamine Oxidase Inhibitors Tricyclic Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) and Other Modern Antidepressants Antipsychotic Drugs Other Neurologic Drugs NSAIDs Drug-Induced Granulomatous Hepatitis Drug-Induced Chronic Hepatitis Diclofenac Minocycline Drug-Induced Acute Cholestasis Importance, Types of Reactions, and Diagnosis Cholestasis without Hepatitis Steroids Oral Contraceptive Steroids Anabolic Steroids Cholestasis with Hepatitis Chlorpromazine Amoxicillin-Clavulanic Acid Fluoroquinolones Cholestatic Hepatitis with Bile Duct Injury Dextropropoxyphene Drug-Induced Chronic Cholestasis Flucloxacillin Fibrotic Bile Duct Strictures Drug-Induced Steatohepatitis and Hepatic Fibrosis Amiodarone Tamoxifen and Other Causes of Drug-Induced Steatohepatitis Cyproterone Acetate Methotrexate Risk Factors Clinicopathologic Features Outcome and Prevention Drug-Induced Vascular Toxicity Azathioprine Liver Tumors References Chapter 89: Liver Disease Caused by Anesthetics, Chemicals, Toxins, and Herbal and Dietary Supplements Anesthetic Agents Halothane Risk Factors Pathology Pathogenesis Course and Outcome Others Jaundice in the Postoperative Period Chemicals Commercial and Industrial Agents Carbon Tetrachloride and Other Chlorinated Aliphatic Hydrocarbons Vinyl Chloride and Other Chlorinated Ethylenes Nonhalogenated Organic Compounds Trinitrotoluene and Other Nitroaromatic Compounds Nitroaliphatic Compounds Polychlorinated Biphenyls and Other Halogenated Aromatic Compounds Miscellaneous Chemical Compounds Pesticides Metals Iron Phosphorus Copper Thorium Dioxide Others Drugs of Abuse Cocaine Others Botanical and Environmental Hepatotoxins Mushrooms Other Foodstuffs Vitamins Vitamin A Niacin Herbal, Dietary, Weight-Loss, and Body-Building Supplements Features of Toxicity Pyrrolizidine Alkaloids Germander Chaparral Pennyroyal Traditional Chinese Herbal Medicines Weight-Loss Products Kava Kava Black Cohosh Greater Celandine Extract Flavocoxid Garcinia cambogia Kratom Hepatoprotection by Herbal Compounds References Chapter 90: Autoimmune Hepatitis Epidemiology Incidence Prevalence Female Predisposition Peak Age of Onset Pathophysiology Genetic Predisposition Epigenetic Factors Autoantigens and Molecular Mimicry Lymphocyte Differentiation and Hepatocyte Loss Clinical Features Symptoms and Physical Findings Laboratory Findings Serology Histology Emerging Biomarkers Diagnosis and Classification Scoring Systems Types Type 1 Type 2 Presentations Asymptomatic Acute or Acute Severe (Fulminant) Autoantibody-Negative Drug-Related Cholestatic Variant (“Overlap”) Syndromes Autoimmune Hepatitis with AMA and Bile Duct Injury or Loss Autoimmune Hepatitis with Cholangiographic Changes of PSC Autoimmune Hepatitis with Unexplained Cholestatic Features Autoimmune Hepatitis with Liver-infiltrating Immunoglobulin G4-staining Plasma Cells Treatment Indications Regimens Pre-treatment Assessment of Thiopurine Methyltransferase Activity Azathioprine Therapy and Pregnancy Adjunctive Interventions Responses Remission Treatment Failure Incomplete Response Drug Toxicity Other Complications Treatment Withdrawal Relapse Sustained Remission Second-Line Treatments High-Dose Glucocorticoids and Azathioprine Mycophenolate Mofetil 6-Mercaptopurine Calcineurin Inhibitors Budesonide Changing Therapeutic Paradigm LT Prognosis References Chapter 91: Primary Biliary Cholangitis Epidemiology Pathogenesis Autoantibodies Genetic Factors Apoptosis Molecular Mimicry Xenobiotics and Other Implicated Agents Clinical Features Asymptomatic Disease Symptomatic Disease Associated Diseases Diagnosis Biochemical Features Serology Histopathology Imaging Natural History Asymptomatic Disease Symptomatic Disease Predicting Survival Antimitochondrial Antibody-Negative Primary Biliary Cholangitis Treatment UDCA Other Drugs Obeticholic Acid Fibrates Prednisolone and Prednisone Budesonide Methotrexate Ineffective Medications and Combination Therapy Management of Complications of Chronic Cholestasis Bone Disease Fat-Soluble Vitamin Deficiency Hyperlipidemia Pruritus Steatorrhea Liver Transplantation Acknowledgments References Chapter 92: Portal Hypertension and Variceal Bleeding Normal Portal Circulation Hemodynamic Principles of Portal Hypertension Increased Intrahepatic Resistance Hyperdynamic Circulation Collateral Circulation and Varices Measurement of Portal Pressure Hepatic Vein Pressure Gradient Splenic Pulp Pressure Portal Vein Pressure Endoscopic Variceal Pressure Detection of Varices EGD US CT MRI EUS Causes of Portal Hypertension Common Cirrhosis Schistosomiasis Extrahepatic Portal Vein Thrombosis Idiopathic Portal Hypertension Cardiac Cirrhosis Less Common Nodular Regenerative Hyperplasia Partial Nodular Transformation of the Liver Fibropolycystic Liver Disease Sarcoidosis Malignancy Splanchnic Arteriovenous Fistula HHT Clinical Assessment Treatment Pharmacologic Therapy Vasopressin and Its Analogs Somatostatin and Its Analogs β-Adrenergic Blocking Agents Combined α- and β-Adrenergic Blocking Agents Nitrates Drugs That Decrease Intrahepatic Vascular Resistance Endoscopic Therapy Sclerotherapy Variceal Ligation Detachable Snares and Clips Balloon Tamponade and Stents TIPS Follow-Up Evaluation Selection of Patients Balloon-Occluded Retrograde Transvenous Obliteration Surgical Therapy Non-Shunt Procedures Esophageal Transection Devascularization Procedures Portosystemic Shunts Selective Shunts Partial Portosystemic Shunts Portacaval Shunts Mesenterico–Left Portal Venous Bypass Management of Specific Causes of Portal Hypertension-Related Bleeding Esophageal Varices Natural History Prevention of Bleeding Pharmacologic Endoscopic Control of Acute Bleeding Prevention of Rebleeding Gastric Varices Natural History Prevention of Bleeding Control of Acute Bleeding Prevention of Rebleeding Ectopic Varices Treatment Portal Hypertensive Gastropathy and Gastric Vascular Ectasia Treatment Other Nonvariceal Causes References Chapter 93: Ascites and Spontaneous Bacterial Peritonitis Pathogenesis of Ascites in Cirrhosis Sodium Retention and Extracellular Fluid Volume Expansion Portal Hypertension Systemic Circulatory Dysfunction The Renin-Angiotensin-Aldosterone System Sympathetic Nervous System Systemic Inflammation Diagnosis Laboratory Tests Assessment of Renal Sodium Excretion Abdominal US Ascitic Fluid Analysis Differential Diagnosis of Ascites Prognosis Complications of Ascites Management of Ascites in Cirrhosis Uncomplicated Ascites Grade 1 Ascites Grade 2 Ascites Sodium Restriction Diuretics Grade 3 Ascites Complications of Diuretic Therapy Refractory Ascites Large-Volume Paracentesis Diuretics TIPS Other Therapies Pharmacologic Agents Alfapump System Hepatic Hydrothorax Contraindicated Drugs Nonselective β-Receptor Antagonists Spontaneous Bacterial Peritonitis Pathogenesis Alterations in the Gut-Liver Axis Cirrhosis-Associated Immune Dysfunction Local Factors Diagnosis Treatment General Management Antibiotics Prevention of Acute Kidney Injury Prophylaxis Primary Secondary References Chapter 94: Hepatic Encephalopathy, Hepatorenal Syndrome, Hepatopulmonary Syndrome, and Other Systemic Complications of Liver Disease Hepatic Encephalopathy Pathophysiology Clinical Features and Classification Diagnosis Treatment Hepatorenal Syndrome Pathophysiology Splanchnic Arterial Vasodilatation Renal Arterial Vasoconstriction Cardiac Dysfunction Clinical Features and Diagnosis Prevention and Treatment Medical Therapy Radiologic and Surgical Therapy TIPS LT Other Therapies Hepatopulmonary Syndrome and Portopulmonary Hypertension Pathophysiology Hepatopulmonary Syndrome Portopulmonary Hypertension Clinical Features and Diagnosis Hepatopulmonary Syndrome Portopulmonary Hypertension Treatment Hepatopulmonary Syndrome Medical Therapy Radiologic Therapy LT Portopulmonary Hypertension Medical Therapy LT Cirrhotic Cardiomyopathy Pathophysiology Clinical Features and Diagnosis Treatment Endocrine Dysfunction Adrenal Insufficiency Gonadal Dysfunction Thyroid Dysfunction Bone Disease Coagulation Disorders Prolongation of the Prothrombin Time Thrombocytopenia Dysfibrinogenemia Endogenous Anticoagulants Thromboelastography References Chapter 95: Acute Liver Failure Definition Etiology and Epidemiology Drugs Acetaminophen Idiosyncratic Reactions Viral Infections Uncommon Causes Pregnancy-Related ALF Vascular Disorders Hyperthermia Autoimmune Hepatitis Wilson Disease Mushroom Poisoning Diagnosis Clinical Features Encephalopathy Intracranial Hypertension and Cerebral Edema Hemodynamic Changes and Circulatory Failure Infection Acute Kidney Injury Hematologic Abnormalities Approach to Management Overall Strategy General Measures Prognosis Liver Transplantation Treatment of Complications Neurologic Complications Infection Hemodynamic Instability and Hypoxemia Acute Kidney Injury Coagulopathy Metabolic Disorders Nutritional Deficiencies Extracorporeal Liver Support References Chapter 96: Hepatic Tumors and Cysts Malignant Tumors HCC Epidemiology Etiology and Pathogenesis HBV HCV Cirrhosis Aflatoxin B1 Other Conditions Clinical Features Paraneoplastic Manifestations Diagnosis Serum Tumor Markers AFP Fucosylated AFP Des-γ-Carboxy Prothrombin Other Markers Imaging US CT MRI PET Hepatic Angiography Laparoscopy Pathology Gross Appearance Microscopic Appearance Well-Differentiated Moderately-Differentiated Undifferentiated Progenitor Cell HCC Metastases Fibrolamellar HCC Staging Natural History and Prognosis Treatment Surgical Resection LT Local Ablation Chemoembolization Chemotherapy Alternative Techniques and Combinations of Therapies Surveillance Prevention Intrahepatic Cholangiocarcinoma Epidemiology Etiology and Pathogenesis Clinical Features Diagnosis Pathology Treatment and Prognosis Hepatoblastoma Epidemiology Etiology and Pathogenesis Clinical Features Diagnosis Pathology Treatment and Prognosis Angiosarcoma Epidemiology Etiology and Pathogenesis Clinical Features Diagnosis Pathology Complications and Prognosis Treatment Epithelioid Hemangioendothelioma Epidemiology Clinical Features Diagnosis Pathology Complications and Prognosis Treatment Others Hepatic Metastases Epidemiology and Etiology Clinical Features Diagnosis Pathology Macroscopic Appearance Microscopic Appearance Treatment and Prognosis Benign Tumors Hepatocellular Adenoma Epidemiology Etiology and Pathogenesis Clinical Features Diagnosis Pathology Treatment and Prognosis Cavernous Hemangioma Epidemiology Clinical Features Diagnosis Pathology Treatment Infantile Hemangioendothelioma Epidemiology Clinical Features Diagnosis Pathology Treatment and Prognosis Others Tumor-Like Hepatic Lesions Focal Nodular Hyperplasia Epidemiology Pathogenesis Clinical Features Diagnosis Pathology Treatment Others Hepatic Cysts Simple Cysts Polycystic Liver Disease Epidemiology Etiology and Pathogenesis Clinical Features Diagnosis Treatment Autosomal Recessive Polycystic Kidney Disease von Meyenburg Complexes Caroli Disease Approach to the Patient with an Hepatic Mass References Chapter 97: Liver Transplantation Indications Listing Criteria and Policies of the United Network for Organ Sharing Contraindications Transplant Evaluation and Listing Disease-Specific Indications Hepatic Malignancy Alcohol-Associated Liver Disease NAFLD Hepatitis C Hepatitis B Cholestatic Liver Disease Autoimmune Hepatitis ALF Metabolic Disorders Vascular Disorders Others Surgical Aspects Native Hepatectomy Live-Donor LT Immunosuppression Postoperative Course Initial Phase to Discharge from the Hospital Following Discharge from the Hospital Long-Term Management General Preventive Measures Immunizations and Antibiotic Prophylaxis Hepatic Retransplantation References Part X: Small and Large Intestine Chapter 98: Anatomy, Histology, Embryology, and Developmental Anomalies of the Small and Large Intestine Anatomy Macroscopic Features Small Intestine Colon and Rectum Anal Canal Vasculature Lymphatic Drainage Extrinsic Innervation Microscopic Features General Considerations Mucosa Submucosa Muscularis Propria Serosa Microscopic Organization Small Intestine Colon Anal Canal Vasculature Lymph Vessels Nerves Embryology Intestinal Development Molecular Regulation of Intestinal Morphogenesis Intestinal Tube Formation Epithelial Cells and Villus Formation Proliferation and Differentiation of the Epithelium Specific Structures and Systems Duodenum Midgut Mesentery Hindgut Arterial System Venous System Lymphatic System Enteric Nervous System Clinical Implications Abnormalities in Normal Embryologic Development Abdominal Wall Omphalocele Gastroschisis Omphalomesenteric (Vitelline) Duct Abnormalities Meckel Diverticulum Omphalomesenteric (Vitelline) Cyst Patent Omphalomesenteric (Vitelline) Duct Omphalomesenteric Band Vitelline Blood Vessel Remnants Malrotations Classification Associated Abnormalities Diagnosis and Management Proliferation Enteric Duplication Intestinal Atresia and Stenosis Anorectum Anocutaneous Fistula Rectourethral Fistula Rectovesical Fistula Vestibular Fistula Anorectal Agenesis (Imperforate Anus) Without Fistula Rectal Agenesis (Atresia) Anal Stenosis Persistent Cloaca Associated Abnormalities Enteric Nervous System Hirschsprung Disease Pathogenesis Failure of Migration Colonic Microenvironment Changes Clinical Features Diagnosis Management Intestinal Neuronal Dysplasia Chronic Intestinal Pseudo-Obstruction Miscellaneous and Genetic Defects Microvillus Inclusion Disease Intestinal Epithelial Dysplasia Congenital Glucose and Galactose Malabsorption Congenital Sucrase and Isomaltase Deficiency Congenital Lactase Deficiency Congenital Chloride Diarrhea (Chloridorrhea) Congenital Sodium Diarrhea Cystic Fibrosis References Chapter 99: Small Intestinal Motor and Sensory Function and Dysfunction Anatomy Normal Small Intestinal Motor and Sensory Function Smooth Muscle Interstitial Cells of Cajal Neurons Intrinsic Neurons Intrinsic Afferent Supply Efferent Supply Interneurons Extrinsic Neurons Afferent Supply Efferent Supply Central Connections of Neural Control Elements Gastrointestinal Hormones Integrated Control of Motility Peristalsis Interdigestive Motor Complex Abnormal Motor and Sensory Function Smooth Muscle Dysfunction Intrinsic Neural Dysfunction Extrinsic Afferent Dysfunction Measurement of Small Intestinal Motility Basic Principles Evaluation of Single Cell Functions Recording of Muscle Contractions In Vivo Techniques Manometry Magnetic Resonance Imaging Ultrasound Wireless Motility Capsule Endoluminal Image Analysis Small Intestinal Transit Studies Fluoroscopy Multi-Channel Intraluminal Impedance Scintigraphy Breath tests Normal in Vivo small Intestinal Motility Patterns Control of Small Intestinal Contractions Propagation of Contractions Along the Small Intestine Integrated Patterns of Motility Fed motor Pattern Radiologic Observations Transit Time Observations Manometric Observations Fasting Motor Pattern Radiologic Observations Transit Time Observations Manometric Observations Clinical Approach Consequences of Disordered Small Intestinal Motility Approach to Patients with Possible Small Intestinal Motor Dysfunction References Chapter 100: Colonic Motor and Sensory Function and Dysfunction Methods To Record Colonic Motility Anatomy and Basic Control Mechanisms of the Colon and Anorectum Macroscopic Structure of the Colon Structure and Activity of Colonic Smooth Muscle Structure Spontaneous Activity Interstitial Cells of Cajal Ion Channels in Colonic Smooth Muscle Innervation of the Colon Enteric Nervous System (ENS) Primary Afferent Neurons Motor Neurons Interneurons Sympathetic Innervation Parasympathetic Innervation Extrinsic Afferent Pathways Anorectal Anatomy and Innervation Relationships Between Cellular Events, Pressure, and Flow Colonic and Anorectal Motor Patterns Nonpropagating Motor Patterns Propagating Motor Patterns Rectal Motor Complexes Regional Variation of Propagating Sequences Regulation of Colonic Filling and Transit Role of the Ileocecal Junction The Colon as a Storage Organ Relationships Between Colonic Motor Patterns and Flow Defecation Rectal Filling, Capacitance, Accommodation, and Motility Anorectal Motility During Defecation Modulators of Colonic Motility Physiologic Pharmacologic Nonpharmacologic Disorders Of Colonic Motility Constipation Diarrhea Irritable Bowel Syndrome Colonic Motility Disturbances Secondary to Nonmotor Intestinal Disorders References Chapter 101: Intestinal Electrolyte Absorption and Secretion Intestinal Architecture and Transport Basic Epithelial Cell Model Segmental Heterogeneity of Transport Movement Across the Intestinal Epithelium Tight and Leaky Epithelia Transepithelial Transport Transcellular Transport Water Movement Channels, Carriers, and Pumps Ion Transporters Apical Sodium Channel Nutrient-Coupled Sodium Transport Sodium-Hydrogen Exchangers Electroneutral Sodium Chloride Absorption Chloride (Anion) Absorption Chloride Secretion Chloride Channels CFTR Chloride Channel ClC Family of Chloride Channels Calcium-Activated Chloride Channels Potassium Transport Bicarbonate Transport Short-Chain Fatty Acid Transport Extracellular Regulation: Microbial, Autocrine, Luminal, Paracrine, Immunologic, Neural, and Endocrine Systems (Malpines) Microbiome and Luminal Factors Autocrine, Endocrine, Paracrine, and Juxtacrine Regulation Neural Regulation Immunologic and Inflammatory Regulation Systemic Effects Osmotic Effects Specific Regulatory Factors Absorptive Factors Secretory Factors Eicosanoids Serotonin and Adenosine Guanylin and Nitric Oxide Microbiota and Microbial Pathogens Bile Acids and Long-Chain Fatty Acids Intracellular Mediators Epithelial Regulation in Context References Chapter 102: Digestion and Absorption of Carbohydrate, Protein, and Fat An Overview of the Digestive Process Nutrient Transporters Carbohydrates Types of Carbohydrates in Normal Diet Glycemic Index Digestion of Carbohydrates Luminal Digestion Membrane Digestion Absorption of Monosaccharides Knockout Mouse Models for Intestinal Sugar Transporters Defects in Carbohydrate Digestion Defects in Carbohydrate Absorption Dietary Fiber and Colonic Bacteria Proteins Dietary Intake Differences Between Carbohydrate and Protein Digestion and Absorption Digestion Luminal Digestion Membrane Digestion Intracellular Digestion Absorption of Small Peptides Absorption of Amino Acids Amino Acid Transporters in the Brush-Border Membrane Amino Acid Transporters in the Basolateral Membrane Function of Brush-Border Peptidases in the Transport of Peptides and Amino Acids Amino Acid Transporters in the Colon Defects in Protein Digestion Defects in Protein Absorption Polymorphisms in PepT1 (SLC15A1) Disorders of Amino Acid Absorption Hartnup Disease Cystinuria Lysinuric Protein Intolerance Fat Dietary Lipids Unique Features of Fat Digestion and Absorption Digestion of Fat in the GI Lumen Assembly of Fat-Digestion Products into Micelles Transport Systems for Fat-Digestion Products Fatty Acids Cholesterol Reassembly of Fat-Digestion Products into Chylomicrons in Enterocytes Re-synthesis of Triglycerides, Cholesteryl Esters, and Phospholipids Assembly of Chylomicrons—Apolipoprotein B-48 Assembly of Chylomicrons—Microsomal Triglyceride Transfer Protein Chylomicrons Versus Very Low Density Lipoprotein Secretion of Chylomicrons and Very Low Density Lipoprotein into Lacteals Medium-Chain Fatty Acids and Medium-Chain Triglycerides Acknowledgments References Chapter 103: Digestion and Absorption of Micronutrients Water-Soluble vitamins Ascorbate (Vitamin C) Metabolic role and effect of deficiency Sources and Recommended Daily Allowance Digestion and Absorption Physiologic Aspects Molecular Aspects Intestinal Absorption Cell Biology Aspects Regulatory Aspects Biotin (Vitamin B7) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Physiologic Aspects Digestion and Absorption Molecular Aspects Cell Biology Aspects Regulatory Aspects Clinical Pathophysiology of Intestinal Biotin Uptake Cobalamin (Vitamin B12) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Digestion and Absorption Physiologic Aspects Molecular Aspects Regulatory Aspects Clinical Pathophysiology of Intestinal Cobalamin Absorption Folate (Vitamin B9) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Digestion and Absorption Physiologic Aspects Molecular Aspects Cell Biology Aspects Regulatory Aspects Clinical Pathophysiology of Intestinal Folate Absorption Niacin (Vitamin B3, Nicotinic Acid) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Absorption Cell Biology Aspects Regulatory Aspects Pantothenic Acid (Vitamin B5) Metabolic Role and Sources Intestinal Digestion and Absorption Cell Biology Aspects Regulatory Aspects Pyridoxine (Vitamin B6) and Derivatives Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Absorption Cell Biology Aspects Regulatory Aspects Riboflavin (Vitamin B2) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Digestion and Absorption Physiologic Aspects Molecular Aspects Cell Biology Aspects Regulatory Aspects Thiamine (Vitamin B1) Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Absorption Physiologic Aspects Molecular Aspects Cell Biology Aspects Regulatory Aspects Clinical Pathophysiology of Intestinal Thiamine Absorption Fat-Soluble Vitamins Vitamin A Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Clinical Pathophysiology of Intestinal Absorption of Vitamin A Vitamin D Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Absorption Physiologic Aspects Metabolic Aspects Regulatory Aspects Vitamin E Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Intestinal Absorption Physiologic Aspects Clinical Pathophysiology of Intestinal Vit E Absorption Vitamin K Metabolic Role and Effect of Deficiency Sources and Recommended Daily Allowance Clinical Pathophysiology of Intestinal Vit K Absorption Minerals and Trace Elements Calcium Magnesium Iron Zinc Copper Iodine Selenium Other Trace Elements References Chapter 104: Maldigestion and Malabsorption Etiology and Pathophysiology Fats Defective Mixing Reduced Solubilization of Fat Decreased Lipolysis Decreased Mucosal Absorption and Chylomicron Formation Defective Lymphatic Transport of Chylomicrons Proteins and Amino Acids Defective Intraluminal Proteolysis Defective Mucosal Hydrolysis of Peptides and Decreased Absorption of Oligopeptides and Amino Acids Carbohydrates Defective Intraluminal Hydrolysis of Carbohydrates Mucosal Defects of Carbohydrate Digestion and Absorption Vitamins Fat-Soluble Vitamins Water-Soluble Vitamins Vitamin B12 (cobalamin) Folate Other Water-Soluble Vitamins Minerals Calcium Magnesium Iron Zinc Others Mechanisms that Compensate for Malabsorption Role of the Colon Colonic Salvage of Incompletely Absorbed Carbohydrates Role of the Colon in Fat Malabsorption Colonic Salvage of Calcium Role of Intestinal Transit in the Salvage of Malabsorbed Nutrients Clinical Features and Evaluation Suspecting and Confirming the Presence of Malabsorption History and Physical Examination Laboratory Findings Diagnostic Approach Clinical Clues to the Presence of Specific Diseases Anatomic Investigations Endoscopy, Biopsy, and Duodenal Aspiration Endoscopy Biopsy Aspiration Video Capsule Endoscopy and Balloon Enteroscopy Abdominal Imaging Small Bowel Follow-Through and Small Bowel Enteroclysis Abdominal Computed Tomography Magnetic Resonance Imaging of the Small Intestine Ultrasonography Examination Other Studies Noninvasive Evaluation of GI Digestive and Absorptive Function Fat Malabsorption Quantitative Fecal Fat Analysis Semi-Quantitative Fat Analysis Qualitative Fecal Fat Analysis Breath Tests for Fat Malabsorption Carbohydrate Malabsorption Protein Malabsorption Vitamin B12 (Cobalamin) Malabsorption Schilling Test Serum Test for Vitamin B12 and Folate Deficiency Small Intestinal Bacterial Overgrowth Exocrine Pancreatic Insufficiency Bile Acid Malabsorption Measurement of Fecal Bile Acid Output 14Carbon-Taurocholate Bile Acid Absorption Test Selenium-75-Labeled Homotaurocholic Acid Test D-xylose Test Intestinal Permeability Tests 13Carbon Breath Tests Malabsorption in Specific Situations and Disease States Lactose Malabsorption Fructose Malabsorption and Intolerance Other Poorly Absorbable Carbohydrates Bile Acid Malabsorption Amyloidosis Drugs and Food Supplements Angiotensin II Receptor Blockers Gastric Resection or Bariatric Surgery Gastric Resection Bariatric Surgery Aging Connective Tissue Diseases PSS SLE and Other Connective Tissue Diseases Congenital Defects Amino Acid Transport Defects Disaccharidase Deficiency and Transport Defects for Monosaccharides Congenital Disorders of Lipid Absorption Congenital Disorders of Cobalamin Absorption Intestinal Enterokinase Deficiency Primary Immunodeficiency Diseases Selective Immunoglobulin a Deficiency Common Variable Immunodeficiency X-linked Infantile Agammaglobulinemia (Bruton Agammaglobulinemia) Immune Dysregulation-Polyendocrinopathy-Enteropathy–X-Linked Syndrome Other Congenital Immunodeficiency Syndromes Neurofibromatosis Type 1 (Von Recklinghausen Disease) Autoimmune Enteropathy and Nongranulomatous Chronic Idiopathic Enterocolitis Endocrine and Metabolic Disorders Adrenal Insufficiency (Addison Disease) Enteroendocrine Deficiency Autoimmune Polyendocrinopathy, Candidiasis, Ectodermal Dystrophy (APECED) Hyperthyroidisxm and Autoimmune Thyroid Disease Diabetes Mellitus Metabolic Bone Disease General Approach to Management References Chapter 105: Small Intestinal Bacterial Overgrowth Definition Pathogenesis Mucosal Injury Luminal Competition With Host for Nutrients Bacterial Metabolism Causes Intestinal Dysmotility Altered Anatomy Hypochlorhydria Immune Deficiencies Multifactorial Causes Chronic Pancreatitis Celiac Disease Liver Disease Disorders With an Unclear or Undefined Relationship to SIBO Clinical Features Diagnosis Small Bowel Aspirate/Culture Breath Testing Other Tests Treatment Nutritional Management Microbial Modification References Chapter 106: Short Bowel Syndrome Etiology Incidence and Prevalence Pathophysiology Loss of Absorptive Surface Area Nutrient Malabsorption Water and Electrolyte Malabsorption Loss of Site-Specific Transport Processes Loss of Site-Specific Enteroendocrine Cells and GI Hormones Loss of the Ileocecal Valve Intestinal Adaptation to Resection Medical Management Limited Ileal Resection Extensive Small Intestinal Resection and Partial Colectomy Fluid and Electrolytes Diet Home Parenteral Nutrition Complications Gallstones Liver Disease Calcium Oxalate Kidney Stones D-Lactic Acidosis Others Surgical Management Intestinal Lengthening Procedures Intestinal Transplantation Pharmacologic Enhancement of Bowel Adaptation Survival and Quality of Life References Chapter 107: Celiac Disease Definitions History of Celiac Disease Epidemiology Pathology Pathogenesis Gluten as Antigen Other Environmental Factors Genetic Factors Immune Factors Clinical Features Childhood Presentation Adulthood Presentation GI Features Extraintestinal Features Anemia Low Bone Density Neuropsychiatric Symptoms Gynecologic and Fertility Problems Physical Findings Diagnosis Serology Immunoglobulin A Endomysial Antibody Tissue Transglutaminase Antibodies Deamidated Gliadin Antibodies Clinical Application of Serologic Tests Genetic Testing for HLA DQ2/DQ Small Intestinal Biopsy Gluten Challenge Other Laboratory Studies Radiology Differential Diagnosis Diseases Associated With Celiac Disease Dermatitis Herpetiformis Other disease associations Treatment Gluten-Free Diet (GFD) Dietary Supplementation Glucocorticoids Monitoring of Patients on Treatment Nonresponsive Celiac Disease Refractory Celiac Disease Ulcerative Jejunoileitis Collagenous Sprue Treatment Complications Celiac Disease and Malignancy Prognosis Future Therapies Acknowledgment References Chapter 108: Tropical Diarrhea and Malabsorption Infectious Diarrhea In The Tropics Tropical Sprue Definition History Epidemiology Etiopathogenesis Clinical Features Histopathology Pathophysiology Diagnosis Treatment Distinction of Tropical Enteropathy From Tropical Sprue Other Diseases That May Cause Malabsorption in the Tropics Giardiasis Other Protozoan Infections Helminthic Infections Fungal Infections HIV Infection and AIDS Intestinal TB Crohn Disease Celiac Disease Primary Immunodeficiency Syndromes Immunoproliferative Small Intestinal Disease And Small Bowel Lymphoma Tropical Pancreatitis Approach To The Patient With Suspected Malabsorption References Chapter 109: Whipple Disease History Epidemiology Microbiology and Genomics Pathogenesis and Immunology Clinical Features Small Intestine and Lymphatic System CNS Cardiovascular System Musculoskeletal System Other Clinical Manifestations Emerging Disease Associations Pathology Small Intestine Extraintestinal Pathology Diagnosis Differential Diagnosis Treatment and Prognosis References Chapter 110: Infectious Enteritis and Proctocolitis Susceptibility to Intestinal Infection Host Defense Factors Bacterial Factors General Principles of Infectious Enteritis and Proctocolitis Evaluation Risk Factors Differentiating IBD and Infectious Diarrhea Laboratory Diagnosis Enterotoxigenic Pathogens Vibrio cholerae Microbiology Cholera Toxin Epidemiology Pathogenesis Clinical Features Treatment Vaccines Other Vibrio Species Non-O1/O139 Vibrio cholerae Vibrio parahaemolyticus Epidemiology Clinical Features Additional Vibrio Species Treatment Aeromonas Species Epidemiology Clinical Features Treatment Plesiomonas shigelloides Escherichia coli Species Enteropathogenic E. coli (EPEC) Enterotoxigenic E. coli (ETEC) Pathogenic Mechanisms Epidemiology Clinical Features Immunity and Vaccines Diagnosis and Treatment Enteroinvasive Escherichia coli (EIEC) Shiga Toxin (STx)-producing E. coli (STEC) Epidemiology Pathogenic Mechanisms Clinical Features Diagnosis Treatment Enteroaggregative E. coli (EAEC) Diffusely Enteroadherent Escherichia coli (DAEC) Invasive Pathogens Shigella Species Microbiology Epidemiology Pathogenic Mechanisms Clinical Features Diagnosis Treatment Nontyphoidal Salmonella Species Microbiology Epidemiology Pathogenic Mechanisms Predisposing Conditions Clinical Features Treatment Typhoid Fever Microbiology Pathogenic Mechanisms Epidemiology Clinical Features Carrier State Diagnosis Treatment Chronic Carriers Vaccines Campylobacter Species Epidemiology Pathogenic Mechanisms Clinical Features Diagnosis Treatment Yersinia enterocolitica Pathogenic Mechanisms Epidemiology Clinical Features Treatment Sexually Transmitted Infectious Proctitis Viral Pathogens Rotavirus Pathology and Pathogenesis Epidemiology Clinical Features Diagnosis Treatment and Vaccination Caliciviruses (Norovirus and Sapovirus) Epidemiology Clinical Features Diagnosis Treatment and Prevention Enteric Adenovirus and Astrovirus Travelers’ Diarrhea Tuberculosis of the Intestinal Tract Overview of Treatment Fluid Therapy Diet Antimicrobial Drugs Nonspecific Therapy References Chapter 111: Food Poisoning Approach to the Patient Bacterial Food Poisoning Clostridium perfringens Microbiology Epidemiology and Pathogenic Mechanisms Clinical Features Enteritis Necroticans Staphylococcus aureus Microbiology Epidemiology Pathogenic Mechanisms Clinical Features Bacillus cereus Diarrhea Syndrome Vomiting Syndrome Vibrio species Listeria monocytogenes Clostridium botulinum Epidemiology Pathogenic Mechanisms Clinical Features Diagnosis Treatment Bacillus anthracis Microbiology Epidemiology Pathogenic Mechanisms Clinical Features Treatment and Prevention Fish Poisoning Ciguatera Poisoning Scombroid Poisoning Tetrodotoxin Poisoning Shellfish-Poisoning Syndromes Paralytic Shellfish Poisoning (PSP) Neurologic Shellfish Poisoning (NSP) Diarrheal Shellfish Poisoning (DSP) Amnesic Shellfish Poisoning (ASP) Mercury Poisoning References Chapter 112: Antibiotic-Associated Diarrhea and Clostridioides difficile Infection Antibiotic-Associated Diarrhea Etiology Prevention and Treatment Pseudomembranous Enterocolitis Epidemiology Pathogenesis Alteration of the Colonic Microbiota C. difficile Toxins Immune Response to C. Difficile Other Risk Factors For CDI CDI in IBD Clinical Features Diagnosis Whom to Test Whom Not to Test How to Test Enzyme-Linked Immunoassays Two-Step Testing NAAT Tissue Culture Cytotoxicity Assay C. difficile Culture Sigmoidoscopy and Colonoscopy Miscellaneous Laboratory Tests Treatment Treatment for an Initial Episode of CDI Vancomycin Fidaxomicin Metronidazole Other Antimicrobial Agents Fulminant (Severe Complicated) CDI Surgery Recurrent CDI Conservative Therapy Standard Therapy With Metronidazole, Vancomycin, or Fidaxomicin Prolonged Antibiotic Regimens for First or Subsequent Episodes of Recurrent CDI Sequential Therapy With Vancomycin Followed by Rifaximin IMT Immunization Against C. difficile Toxins Bezlotoxumab: Antitoxin B IgG Human Monoclonal Antibody C. difficile Vaccines Probiotic Therapy Overall Approach to Recurrent CDI References Chapter 113: Intestinal Protozoa Entamoeba histolytica Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Other Amebae That Infect the Human Intestine Giardia intestinalis Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Dientamoeba fragilis Blastocystis hominis Cryptosporidium Species Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Cyclospora cayetanensis Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Cytoisospora belli (Previously Isospora belli) Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Microsporidia Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention Trypanosoma cruzi (Chagas Disease or American Trypanosomiasis) Epidemiology Pathogenesis, Pathology, and Immunology Clinical Features Diagnosis Treatment Control and Prevention References Chapter 114: Intestinal Worms Nematodes Ascaris lumbricoides Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Strongyloides stercoralis Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Capillaria (Paracapillaria) philippinensis Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Necator americanus, Ancylostoma duodenale, Ancylostoma Ceylanicum, and Ancylostoma Caninum (Hookworms) Necator americanus and Ancylostoma duodenale Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Ancylostoma ceylanicum Epidemiology, Life Cycle, and Clinical Features Pathophysiology, Diagnosis, and Treatment Ancylostoma Caninum Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Trichuris trichiura (Whipworm) Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Enterobius vermicularis (Pinworm) Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Trichinella species Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Anisakis simplex complex Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Oesophagostomum bifurcum, O. Stephanostomum (Nodule Worm) Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Cestodes Diphyllobothrium Species Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Taenia saginata, Taenia asiatica, and Taenia solium Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment Hymenolepis nana and Hymenolepis diminuta Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Dipylidium Caninum Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Trematodes Intestinal Flukes Fasciolopsis buski Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Heterophyes Species Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Echinostoma Species Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Liver Flukes Clonorchis Sinensis, Opisthorchis viverrini, and Opisthorchis felineus Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Fasciola hepatica and Fasciola gigantica Epidemiology and Life Cycle Clinical Features and Pathophysiology Diagnosis and Treatment Blood Flukes Epidemiology Life Cycle Clinical Features and Pathophysiology Diagnosis Treatment References Chapter 115: Epidemiology, Pathogenesis, and Diagnosis of Inflammatory Bowel Diseases Epidemiology Etiology and Pathogenesis Genetics Family History Susceptibility Genes Environmental Factors Immunobiology Intestinal Microbiota Intestinal Immune System Epithelial Barrier Antigen Recognition and Immunoregulation Immune Cell Homing to the Intestinal Mucosa Pathologic Features Crohn Disase Aphthae Granulomas Later Pathologic Findings Other Findings UC Clinical Features Disease Location Clinical Features Typical Presentations in Crohn Disease, by Location Unusual Presentations in Crohn Disease, by Location Disease Behavior in Crohn Disease Fistula and Abscess Stricture Classification of Disease Pathophysiology of Common Symptoms and Signs Rectal Bleeding Diarrhea Abdominal Pain Weight Loss and Malnutrition Fever Anemia Extraintestinal Manifestations Musculoskeletal Mucocutaneous Ocular Hepatobiliary Renal and Genitourinary Vascular Others Differential Diagnosis of IBD Differentiating Crohn Disease from UC Differentiating IBD From Intestinal Infections Differentiating IBD From Noninfectious Diseases Establishing the Diagnosis in IBD Endoscopy Radiology Plain Films CT and MRI Measuring Disease Activity in IBD Crohn Disease UC References Chapter 116: Management of Inflammatory Bowel Diseases Medical Therapy Aminosalicylates Aminosalicylate Treatment of Crohn Disease Aminosalicylate Treatment of UC Oral-Administered Therapies Rectally-Administered Therapies Glucocorticoids Glucocorticoid Treatment of Crohn Disease Glucocorticoid Treatment of UC Orally-Administered Therapies Rectally-Administered Therapies Immunomodulators Thiopurines Thiopurine Treatment of Crohn Disease Thiopurine Treatment of UC Methotrexate Methotrexate Treatment of Crohn Disease Methotrexate Treatment of UC Cyclosporine Tacrolimus Alternative Immunomodulators Biologic Therapies Anti-TNF Therapy Anti-TNF Treatment of Crohn Disease Anti-TNF Treatment of UC Optimizing Anti-TNF Response Anti-Adhesion Molecules Natalizumab Vedolizumab Vedolizumab Treatment for Crohn Disease Vedolizumab Treatment for UC Anti IL-12/IL-23 Ustekinumab Crohn Disease Newer Agents Kinase Inhibitors S1P Inhibitors Adjunctive Therapies Antibiotics, Probiotics, and Intestinal Microbiota Transplantation Nutritional Therapy Cytapheresis Surgical Therapy Crohn Disease Prevention of Postoperative Recurrence UC Diseases of the Ileal Pouch Management of Inflammatory Bowel Disease-Related Complications Intraabdominal Abscesses Perianal Disease Strictures and Fibrostenotic Disease Toxic Megacolon Dysplasia and Colorectal Cancer Extraintestinal Manifestations Cutaneous/Oral Ophthalmologic Rheumatologic Metabolic Bone Disease Hepatobiliary Hypercoagulability Anemia Other Extraintestinal Manifestations Management of Inflammatory Bowel Disease in Special Situations Children Fertility and Pregnancy The Older Patient References Chapter 117: Ileostomies, Colostomies, Pouches, and Anastomoses Configuration of an Ileostomy Configuration of a Colostomy Continent Ileostomy (Kock Pouch) Anastomotic Dehiscence and The Ghost Ileostomy Ileal Pouch-Anal Anastomosis Clinical Results Controversies Double-Stapled Versus Hand-Sewn Anastomosis Role of Defunctioning Ileostomy Fertility and Pregnancy Ileal Pouch-Anal Anastomosis and Indeterminate Colitis Impact of Therapy with Biological Agents Minimally Invasive Surgical Techniques Laparoscopic Approach Benefits of the Robotic Approach Pathophysiologic Consequences of Proctocolectomy Fecal Output after Proctocolectomy Functional Sequelae Clinical Consequences of Proctocolectomy Ostomy Complications and Management Ischemia and Necrosis Prolapse Retraction Stenosis Parastomal Hernia Bleeding and Peristomal Varices Complications of Ileal Pouch-Anal Anastomosis Pouchitis and Cuffitis Diagnosis Pathogenesis Treatment Sequelae Pouch Neoplasia Pouch Failure Sexual Dysfunction Quality of Life Long-Term Results Pouch Explantation and Redo Surgery Abdominal Colectomy and Ileorectal Anastomosis Patient Selection Complications Physiology Colostomy in the Management of Ulcerative Colitis Risk-Benefit Analysis Conventional Ileostomy Continent Ileostomy Ileal Pouch-Anal Anastomosis Ileorectal Anastomosis References Chapter 118: Intestinal Ischemia Anatomy of the Splanchnic Circulation Celiac Artery Superior Mesenteric Artery Inferior Mesenteric Artery Collateral and Anastomotic Circulation Pathophysiology and Pathology Acute Mesenteric Ischemia Incidence Clinical Features Laboratory Features and Diagnosis Treatment Specific Types of AMI SMAE NOMI Mesenteric Arterial Occlusive Disease Outcomes Mesenteric Venous Thrombosis Incidence Predisposing Conditions Pathophysiology Clinical Features Diagnosis Acute Mesenteric Venous Thrombosis Chronic Mesenteric Venous Thrombosis Treatment Acute Mesenteric Venous Thrombosis Chronic Mesenteric Venous Thrombosis Prognosis Special Situations Mesenteric Phlebosclerosis Myointimal Hyperplasia of the Mesenteric Veins Focal Segmental Ischemia of the Small Intestine Colonic Ischemia Incidence Pathophysiology and Causes Medications as a Cause of CI Antibiotics Chemotherapeutic Agents Constipation-Inducing Agents Decongestants Diuretics Hormonal Therapies Controlled or Illicit Pharmacologic Agents Interferon Laxatives NSAIDs Psychotropic Medications Serotonin Agonists and Antagonists Pathology Clinical Features and Diagnosis Clinical Course and Treatment Gangrene Segmental Colitis Ischemic Stricture Universal Fulminant Colitis Outcome Associations in CI Special Clinical Problems Isolated Ischemia of the Right Colon CI in Patients With Carcinoma of the Colon and Other Potentially Obstructive Lesions Colonic Ischemia in Irritable Bowel Syndrome Colonic Ischemia Complicating Aortic Surgery Chronic Mesenteric Ischemia (Intestinal Angina) Clinical Features Diagnosis Treatment Vasculitis and Angiopathy of the Splanchnic Circulation Allergic Granulomatous Angiitis (Eosinophilic Granulomatosis With Polyangiitis, or Churg-Strauss Syndrome) Behçet Syndrome Thromboangiitis Obliterans (Formerly Buerger Disease) Cogan Syndrome Fibromuscular Dysplasia Henoch-Schönlein Purpura Hypersensitivity Vasculitis Kawasaki Disease Köhlmeier-Degos Disease (Malignant Atrophic Papulosis) Polyarteritis Nodosa HBV Vasculitis (Formerly Hepatitis B–Associated Polyarteritis Nodosa) Rheumatoid Vasculitis SLE Takayasu Disease Acknowledgment References Chapter 119: Intestinal Ulcerations Causes Congenital Diseases Coagulopathic Diseases Inflammatory Diseases of Blood Vessels (Vasculitis) Infectious Diseases Neoplastic Diseases Iatrogenic Injury and Pharmacologic Agents NSAIDs Identifying Small Bowel Ulcers Presentation Capsule Endoscopy Enteroscopy Cross Sectional Imaging Other Radiologic Studies References Chapter 120: Appendicitis Historical Perspective Epidemiology Anatomy and Embryology Pathology Pathogenesis Clinical Features Diagnosis Laboratory Studies Imaging Studies Plain Abdominal Films US CT Overall Approach Clinical Scoring Systems and Computer-Aided Diagnosis Laparoscopy Complications Treatment Outcomes Special Topics The Appendix and UC Crohn Disease of the Appendix Recurrent and Chronic Appendicitis Diverticulitis of the Appendix Epithelial Malignancies of the Appendix Incidental or Prophylactic Appendectomy Acknowledgment References Chapter 121: Diverticular Disease of the Colon Epidemiology Pathology Pathogenesis Colonic Wall Structure Motility Environmental Factors Heritable Factors Asymptomatic Diverticulosis Symptomatic Uncomplicated Diverticular Disease Pathophysiology Clinical Features Diagnosis Treatment 5-Aminosalicylic Acid (5-ASA) Antibiotics and Probiotics Anticholinergics and Antispasmodics Role of Surgery Diverticulitis Pathophysiology Uncomplicated Diverticulitis Clinical Features Diagnosis Imaging Studies Endoscopy Treatment Complicated Diverticulitis Abscess Fistula Obstruction Free Perforation Special Topics Related to Diverticulitis The Young Patient The Older Adult Patient The Immunocompromised Patient Right-Sided Diverticulitis Segmental Colitis Associated with Diverticulosis Diverticular Hemorrhage Pathophysiology Clinical Features Diagnosis and Treatment Colonoscopy Nuclear Scintigraphy, Angiography, and CT Surgery Acknowledgment References Chapter 122: Irritable Bowel Syndrome Definitions Clinical Features History Abdominal Pain Constipation and Diarrhea Bloating and Visible Distention Noncolonic Symptoms Chronicity Physical Examination Epidemiology Prevalence Gender and Race Subgroups Incidence of IBS and Disappearance of Symptoms Impact on Quality of Life and Costs Health Care-Seeking Excess Abdominal Surgery Risk Factors Pathophysiology Altered Motility Visceral Hypersensitivity Abnormal Gas Handling and Abdominal Accommodation Low-Grade Mucosal Inflammation, Immune Activation, and Altered Intestinal Permeability Abnormal 5-hydroxytryptamine Metabolism Food Intolerance Abnormal Intestinal Microbiota Abnormal Bile Acid Metabolism Psychologic Factors CNS Dysregulation Genetic Factors Diagnosis Treatment Education and Support Diet and Lifestyle Medication Anticholinergic and Antispasmodic Agents Laxatives Secretagogues Drugs Acting on Opioid Receptors 5-HT-Receptor Antagonists Antidepressants Antibiotics Probiotics Drugs Acting on Pain Receptors Emerging Drugs Psychologic Treatments Alternative Treatments Prognosis References Chapter 123: Intestinal Obstruction Acute Small Bowel Obstruction Epidemiology and Etiology Pathophysiology Clinical Features Laboratory Findings Radiologic Findings Abdominal Plain Films CT US Magnetic Resonance Imaging Initial Management Specific Causes of SBO Adhesions Principles of Management Hernia Malignancy Intussusception Foreign Body Gallstone Ileus Crohn Disease Radiation Chronic Small Bowel Obstruction Clinical Features Evaluation Management Congenital Malrotation Large Bowel Obstruction Pathophysiology Clinical Features Evaluation Management Volvulus Benign and Malignant Strictures Self-expanding Colonic Stents References Chapter 124: Ileus and Pseudo-Obstruction Syndromes Ileus Epidemiology Risk Factors and Pathophysiology Early Neurogenic Phase Late Inflammatory Phase Pharmacologic Mechanisms Anesthesia Opioids Clinical Features Treatment Prevention Preoperative Nutrition Reducing the Stress Response Mechanical Bowel Preparation Prophylaxis of Postoperative Nausea and Vomiting Intraoperative Nature of Surgery Anesthesia Hemodynamic Management Postoperative NG Tubes, Drains, and Catheters Gum Chewing and Laxative Use Early Oral Intake and Nutrition Postoperative Pain Management Early Mobilization Preset Discharge Criteria Drug Therapy Opioid-Sparing Analgesia Opioid Antagonists Other Agents Acute Colonic Pseudo-Obstruction Epidemiology Pathophysiology Clinical Features Symptoms and Signs Laboratory Studies Differential Diagnosis Treatment Medical Decompression Prevention Chronic Intestinal Pseudo-Obstruction Epidemiology Pathophysiology Enteric Neuropathies Enteric Myopathies Enteric Mesenchymopathies Primary Causes Familial Intestinal Pseudo-Obstruction Familial Visceral Myopathies Familial Visceral Neuropathies Mitochondrial Disorders Other Primary Etiologies Secondary Causes Progressive Systemic Sclerosis Dermatomyositis and Polymyositis SLE Diabetes Mellitus Parkinson Disease Spinal Cord Injury Neurofibromatosis (Von Recklinghausen Disease) Idiopathic Myenteric Ganglionitis Paraneoplastic Visceral Neuropathies Myotonic Dystrophy Muscular Dystrophy Amyloidosis Chagas Disease Thyroid Disease Hypoparathyroidism Medications Celiac Disease Jejunal Diverticulosis Irradiation of the Intestine Diffuse Lymphoid Infiltration Anorexia Nervosa and Bulimia Clinical Features Complications Malnutrition TPN-Related Disorders SIBO Mechanical Obstruction of the Intestine Pneumatosis Cystoides Intestinalis Mental Health Issues Natural History Diagnosis Imaging Studies Laboratory Tests Endoscopy Manometry Myopathic Pattern Neuropathic Pattern Mechanical Obstruction Surgical Biopsy Treatment Maintaining Nutrition Acute Exacerbations Restoring Intestinal Propulsion SIBO Pain Constipation Surgical Therapy Enteric Dysmotility Megacolon and Megarectum Diagnosis and Management References Chapter 125: Tumors of the Small Intestine Descriptive Epidemiology Biology and Biochemical Changes Risk Factors and Associated Conditions Clinical Features Adenocarcinoma Pathology, Natural History, and Staging Clinical Features Diagnosis Therapy Chemoprevention Endoscopic Therapy Surgery Chemotherapy Other Primary Tumors of the Small Intestine Small Intestine Neuroendocrine Tumors (Carcinoid Tumors) Pathology, Natural History, and Staging Clinical Features Diagnosis Biochemical Markers Imaging Endoscopy Treatment Localized Tumors Tumors with Regional Spread Distant Metastases Mesenchymal Tumors Pathology Natural History and Prognosis Clinical Features and Diagnosis Treatment Lymphomas Clinical Features and Diagnosis Secondary Tumors References Chapter 126: Colonic Polyps and Polyposis Syndromes Conventional Adenomas Epidemiology Prevalence Incidence Anatomic Distribution Multiple Adenomas and Carcinomas Pathology Histologic Features Malignant Potential of Adenomatous Polyps Diminutive Polyps Flat Adenomas Pathogenesis Cellular Growth Molecular Pathogenesis Risk Factors for Adenomas Inherited Susceptibility Diet and Lifestyle Predisposing Conditions Ureterosigmoidostomy Sites Acromegaly Bacterial and Viral Infections The Colonic Microbiome Cholecystectomy Clinical Features Methods for Detection Fecal Occult Blood Testing Fecal Immunochemical Testing Barium Enema Sigmoidoscopy Colonoscopy CT Colonography Stool DNA Testing Treatment Natural History without Treatment Age Distribution Studies Initial Treatment Management of the Malignant Polyp Polyp Recurrence Rates Effect of Polypectomy on CRC Incidence and Mortality Frequency of Surveillance Colonoscopy Sessile Serrasted Adenomas and Hyperplastic Polyps Epidemiology Histopathology Molecular Genetics and Epigenetics Risk Factors Natural History Management Endoscopic Appearance Detection and Removal Non-Neoplastic Polyps and Polypoid Lesions Juvenile Polyps Peutz-Jeghers Polyps Inflammatory Polyps (Pseudopolyps) Mucosal Prolapse Polyps Colitis Cystica Profunda and Superficialis Pneumatosis Cystoides Coli Other Gastrointestinal Polyposis Syndromes Inherited Polyposis Syndromes Adenomatous Polyposis Syndromes Familial Adenomatous Polyposis Clinical Features Clinical Presentation Colonic Findings Upper GI Findings Extra-Intestinal Findings Genotype-Phenotype Correlations Genetic Testing and Counseling Treatment Surgery Medical Treatment Variant Adenomatous Polyposis Syndromes Attenuated Familial Adenomatous Polyposis Turcot Syndrome (Glioma-Polyposis) MUTYH-Associated Polyposis (MAP) Polymerase Proofreading Associated Polyposis NTHL1-Associated Polyposis Hamartomatous Polyposis Syndromes Peutz-Jeghers Syndrome Juvenile Polyposis Syndrome PTEN Hamartoma Tumor Syndromes Cowden Disease Bannayan-Ruvalcaba-Riley Syndrome Serrated Polyposis Syndrome (SPS) Other Inherited Polyposis Syndromes Hereditary Mixed Polyposis Syndrome Intestinal Ganglioneuromatosis and Neurofibromatosis Devon Family Syndrome Basal Cell Nevus Syndrome Non-Inherited Polyposis Syndromes Cronkhite-Canada Syndrome Lymphomatous Polyposis Nodular Lymphoid Hyperplasia References Chapter 127: Colorectal Cancer Epidemiology Etiology Fat, Bile Acids, and Bacteria Fiber Carcinogens and Fecal Mutagens, Vitamins, and Micronutrients Calcium and Vitamin D Arachidonic Acid, Eicosanoids, and COX-2 Chemoprevention Biology Abnormal Cellular Proliferation Molecular Genetics and Biochemical Abnormalities Molecular Genetics Biochemical and Other Changes Familial colorectal cancer Predisposing factors Age Prior Adenoma and Carcinoma Adenoma Carcinoma Family History Inflammatory Bowel Disease Other Associations Pathology Gross Pathology Histopathology Natural history and staging Prognosis Surgical–Pathologic staging Tumor Morphology and Histology Clinical Predictors of Prognosis Clinical features Diagnosis and screening Tests When CRC Is Suspected Principles of Screening Screening Techniques Fecal Occult Blood Testing Proctosigmoidoscopy Colonoscopy, Barium Enema, CT Colonography, and Colon Capsule Endoscopy Plasma- and Serum-Based Tumor Markers Fecal DNA and Genetic Testing Approach to Screening Average-Risk Group High-Risk Groups Non-Polyposis Syndromes and Familial Cancer Prior Adenomas or Colon Cancer IBD Insurance Coverage for Screening Screening Capacity, Screening in Underserved Populations, and Quality Assurance Treatment Surgery Follow-Up Resection of Hepatic Metastases Chemotherapy Adjuvant Chemotherapy Chemotherapy for Advanced Disease Immunotargeted Therapy and Immunotherapy Radiotherapy Endoscopic Therapy Other malignant colonic tumors References Chapter 128: Other Diseases of the Colon Cathartic Colon and the Effect of Laxatives on the Colon Clinical Features Treatment Chemical Colitis Prevention and Treatment Colitis Cystica Profunda and Superficialis Etiology Clinical Features and Diagnosis Treatment Colon Ulcers Dieulafoy-Type Lesions Non-Specific Ulcers Clinical Features Diagnosis Treatment Solitary Rectal Ulcer Syndrome Pathogenesis Diagnosis and Pathology Treatment Stercoral Ulcers Pathogenesis Diagnosis and Pathology Treatment Diversion Colitis Epidemiology Pathology Pathogenesis Diagnosis Treatment Endometriosis Etiology and Pathogenesis Clinical Features Diagnosis Treatment Malakoplakia Etiology Clinical Features and Diagnosis Treatment Microscopic Colitis (Lymphocytic and Collagenous) Epidemiology Pathology Etiology and Pathogenesis Clinical and Laboratory Features Differential Diagnosis Treatment Neutropenic Enterocolitis (Typhlitis) Etiology Clinical Features and Diagnosis Treatment Pneumatosis Coli (Pneumatosis Cystoides Intestinalis) Etiology Clinical Features and Diagnosis Pathology Treatment References Chapter 129: Anal Diseases Anatomy Examination of the Anus and Rectum Inspection Palpation Endoscopy Anoscopy Rigid Proctoscopy Flexible Sigmoidoscopy Hemorrhoids Internal Hemorrhoids Evaluation Treatment Rubber Band Ligation Sclerosing Agents Cryotherapy Infrared Photocoagulation Surgical Therapy External Hemorrhoids and Anal Tags Symptoms and Signs Treatment Special Considerations Anal Fissure Etiology Symptoms, Signs, and Diagnosis Treatment Medical Treatment Surgical Treatment Abscesses and Fistulas Abscess Fistula-in-Ano Treatment Special Fistulas Anal Malignancies Anal Margin Cancers Anal Canal Cancers Melanoma Paget Disease Premalignant Lesions High-Resolution Anoscopy Anal Warts Pruritus Ani Symptoms Diagnosis Treatment Anal Stenosis Etiology Diagnosis Treatment Unexplained Anal Pain Coccydynia Functional Rectal Pain Proctalgia Fugax Levator Ani Syndrome Hidradenitis Suppurativa Treatment Pilonidal Disease References Part XI: Additional Treatments for Patients with Gastrointestinal and Liver Disease Chapter 130: Probiotics Definition and Implications Quality Control Safety Mechanisms of Action Clinical Evidence of Effect Effects in Healthy Adults Effects in GI Diseases and Disorders Conclusions References Chapter 131: Complementary, Alternative, and Integrative Medicine Definition and Epidemiology Types of Therapies Demography of Complementary and Alternative Medicine Users Rationale for Use Gastrointestinal Disorders Amenable to Complementary and Alternative Therapies Nausea and Vomiting Natural Products Mind-Body Medicine Functional Dyspepsia Natural Products IBS Natural Products Mind-Body Medicine IBD Natural Products Mind-Body Medicine Diarrhea and Constipation Natural Products Mind-Body Medicine Liver Disease Natural Products Licorice S-Adenosyl-l-Methionine Silymarin Thymic Extract Ayurvedic Medicine Chinese Herbal Medicine Mind-Body Medicine GI Malignancies Natural Products Mind-Body Medicine Medical Marijuana Safety and Regulation of Complementary and Alternative Medicine Therapies References Chapter 132: Palliative Care Medicine in Patients with Advanced Gastrointestinal and Hepatic Disease What is Palliative Medicine Hospice versus Palliative Care Exploring Goals of Care Prognostication Key Prognostic Variables and Tools in Gastrointestinal and Liver Disease The MELD Score Hepatorenal Syndrome Ascites Hepatic Encephalopathy Common Themes in Palliating Gastrointestinal and Hepatic Diseases Abdominal Pain Nausea and Vomiting Dysphagia Anorexia and Cachexia Constipation and Diarrhea Constipation Diarrhea Intestinal Obstruction Jaundice, Ascites, and Hepatic Encephalopathy Jaundice Ascites Hepatic Encephalopathy GI Bleeding