Contents

Preface

Epidemiology and Natural History of Gallstone Disease

Abstract

1. Introduction

2. Burden of Gallstone Disease

3. Types of Gallstones

4. Natural History of Gallstone Disease

4a. Asymptomatic/Silent Gallstones

4b. Symptomatic Gallstone Disease

4c. Functional (Acalculous) Gallbladder Disease

5. Risk Factors for Gallstone Formation

5a. Ethnicity

5b. Family History and Genetics

5c. Age

5d. Gender and Female Sex Hormones

5e. Obesity

5f. Dyslipidemia, Diabetes Mellitus and the Metabolic Syndrome

5g. Non-Alcoholic Fatty Liver Disease

5h. Cholesterol Metabolism

5i. Rapid Weight Loss

5j. Diet

5k. Total Parental Nutrition (TPN)

5l. Lifestyle Factors and Socioeconomic Status

5m. Drugs

Octreotide

Ceftriaxone

Thiazide Diuretics

Statins

Aspirin

Other Diseases

5n. Risk Factors for Pigment Gallstones

Liver Disease

Crohn’s Disease

Cystic Fibrosis

Other Diseases

6. Gallbladder Disease in Children

Conclusion

References

Gallstone Disease in Japan

Abstract

1. Introduction

2. Epidemiology

3. Pathogenesis and Classification

3.1. Cholesterol Gallstone Pathogenesis

3.1.1. Metabolic Abnormalities

3.1.2. Cholesterol Crystal Nucleation and Growth to Macroscopic Gallstones

3.1.3. Role of Genetics

3.2. Pigment Gallstone Pathogenesis

4. Clinical Features

5. Diagnosis

6. Therapeutic Managements

7. Future Direction

Acknowledgments

References

Physical-Chemistry of Biliary Lipids and Cholesterol Crystallization

Abstract

Abbreviations

1. Introduction

2. Chemical Composition of Bile

3. Physical States of Biliary Lipids

4. Phase Diagrams and Cholesterol Solubility in Bile

5. Cholesterol Nucleation and Crystallization from Supersaturated Bile

6. Nucleation Time (Cholesterol Crystal Detection Time)

7. Factors Influencing Cholesterol Crystallization

Conclusion

Acknowledgments

References

The Pathogenesis, Diagnosis and Management of Biliary Sludge

Abstract

Abbreviations

1. Introduction

2. Epidemiology and Risk Factors

2a. Gender and Pregnancy

2b. Bile Stasis

2c. Rapid Weight Loss and Total Parenteral Nutrition (TPN)

2d. Medications and Surgery

3. Natural History

4. Chemical Composition of Biliary Sludge

5. Pathogenesis of Biliary Sludge

6. Complications of Biliary Sludge

7. Clinical Manifestations and Diagnosis

7a. Imaging Techniques

7b. Bile Microscopy

8. Treatment of Biliary Sludge

8a. Medical Approach

Ursodeoxycholic Acid (UDCA)

Cholecystokinin (CCK)

8b. Surgery

Cholecystectomy

Endoscopic Sphincterotomy

Conclusion

Acknowledgments

References

Pathophysiology of Gallstones

Abstract

1. Introduction

2. Pathogenesis of Cholesterol Gallstones

2a. Biliary Lipid Metabolism

2b. Synthesis and Secretion of Biliary Lipids

2c. Role of Nuclear Receptors

2d. Transport of Biliary Lipids

2e. Enhanced Intestinal Cholesterol Absorption

2f. Role of the Gallbladder

Gallbladder Mucosal Function

Gallbladder Motor Function

2g. Nucleation of Cholesterol Crystals and Growth of Crystals into Stones

2h. Factors Promoting or Inhibiting Cholesterol Nucleation

2i. Genetic Contributions to Cholesterol Gallstone Disease

2j. Role of the Microbiota

2k. Pathogenesis of Cholesterol Gallstones in Pregnancy and Obesity

Pregnancy

Obesity

3. Pathogenesis of Pigment Gallstones

3a. Black Pigment Stones

3b. Brown Pigment Stones

Conclusion

References

Gallbladder Motility Dysfunction on Gallstone Formation

Abstract

Abbreviations

1. Introduction

2. Risk Factors and Pathogenesis of Gallstones

2.1. Cholesterol Gallstones

2.2. Pigment Gallstones

3. Gallbladder Motility in Health

4. Impaired Gallbladder Motor Function

5. Gallbladder Motility and Cholesterol Gallstones

5.1. Evidence in Humans

6. Gallbladder Motility and Pigment Gallstones

7. Clinical Application of Gallbladder Emptying Studies

8. Improving Gallbladder Motility

Conclusion and Perspectives

Acknowledgments

References

The Roles of the Immune System, Inflammation, Infection and the Microbiome on Cholesterol Gallstone Pathogenesis

Abstract

1. Introduction

2. Gallbladder Inflammation: Motility

3. Gallbladder Inflammation: Mucin Gel Accumulation

MUC1

MUC2

MUC3

MUC4

MUC5AC

MUC5B and MUC6

4. Gallbladder Inflammation: Lipid Transporters

5. Inflammation: Alterations in Metabolism, Absorption and Lipid Transport

Intestine

Liver

6. Bacterial Colonization, Infection and Cholesterol Gallstones

Salmonella

Helicobacter

7. Viral Infection and Gallstones

Conclusion

References

The Function of Nuclear Receptors in Cholesterol Gallstone Disease

Abstract

1. Introduction

2. Nuclear Receptors (NRs)

2a. Discovery of NRs

2b. Ligands for NRs

2c. NR Domain Structures

LBD and the AF-2 Domain

DNA Binding Domain (DBD)

AF-1 Domain

3. The Roles of NRs in CGD

3a. Estrogen Receptor (ER)

3b. Farnesoid X Receptor (FXR)

3c. Liver X Receptor (LXR)

3d. Pregnane X Receptor (PXR)

Conclusion

References

The Role of Enterohepatic Circulation of Bile Acids in Cholesterol Gallstone Diseases

Abstract

1. Introduction

2. Bile Acid Synthesis

2a. The Classic Pathway

2b. The Alternative Pathway

2c. Bile Acid Biotransformation in the Intestine

3. The Enterohepatic Circulation of Bile Acids

3a. Hepatic Bile Acid Transport

3b. Intestinal Bile Acid Transport

4. Nuclear Receptors in the Regulation of Cholesterol and Bile Acid Metabolism

4a. Nuclear Receptors

4b. Negative Feedback Inhibition of Bile Acid Synthesis

4c. FXR Regulation of Bile Acid Transport

4d. LXR Regulation of Biliary Cholesterol Secretion

5. Bile Acid Metabolism in the Pathogenesis of Cholesterol Gallstones

5a. Hepatic Bile Acid Synthesis

5b. Bile Acid Signaling in the Gallbladder

5c. FXR Regulation of Biliary Lipid Secretion

5d. Bile Acid Metabolism, Gut Bacteria and Gallstone Disease

Conclusion

References

The Role of Lith Genes in Cholesterol Gallstone Formation

Abstract

Abbreviations

1. Introduction

2. Epidemiological and Genetic Investigations of Cholesterol Cholelithiasis in Humans

3. Identification of Lith Genes by QTL Analysis in Inbred Mice

4. Candidate Genes for Cholesterol Cholelithiasis in Mice

5. Genetic Analysis of LITH Genes from Mice to Humans

Conclusion

Acknowledgments

References

Identification of Gallstone Susceptibility (Lith) Genes in the Inbred Mouse

Model of Cholelithiasis

Abstract

1. Introduction

2. Inbred Mouse Model for Cholesterol Cholelithiasis

3. First Strain Survey and Early Crosses

4. Comprehensive Strain Survey and Systematic Genetic Analysis

5. Analysis of Quantitative Trait Genes

Conclusion

Acknowledgment

References

Heritability of Gallstones in Humans

Abstract

1. Introduction

2. Monogenic Cholelithiasis

3. Polygenic Cholelithiasis

4. Genetic Screening and Counseling

5. Molecular Mechanisms of Gallstone Formation

6. Future Perspectives

Acknowledgment

References

Gallstones in Pregnancy

Abstract

Abbreviations

1. Introduction

2. Epidemiology of Gallstone in Pregnancy

3. Pathophysiology of Gallstone Disease in Pregnancy

4. Other Risk Factors for Cholesterol Gallstones in Pregnancy

5. Diagnosis of Biliary Sludge and Gallstones During Pregnancy

6. Prevention and Treatment of Biliary Sludge and Gallstones in Pregnancy

6.1. Prevention

6.2. Asymptomatic Gallbladder Sludge and Gallstones

6.3. Treatment of Symptomatic Uncomplicated Gallbladder Sludge and Gallstones

6.4. Treatment of Complicated Gallbladder Sludge and Gallstones

6.5. Biliary Pancreatitis

6.6. Cholecystectomy

6.7. Postpartum Approach

Conclusion

Acknowledgments

References

Diet and Gallstones

Abbreviations

Abstract

1. Introduction

2. The Burden of Obesity and Metabolic Syndrome

3. Dietary Components and Gallstones

3.1 Diet Characteristics

3.2 Carbohydrate Intake

3.3 Fish Consumption

3.4 Vegetables, Fruits, Calcium, Vitamin C, and Legumes

3.5 Coffee

3.6 Eating Pattern

3.7 Alcohol

3.8 Gut Microbiota and Nutrients

Conclusion

Acknowledgments

References

The Effects of Diet and Obesity on Cholesterol Gallstone Disease

Abstract

1. Introduction

2. Epidemiological Associations of Dietary Factors with Gallstone Disease

3. The Effect of Obesity on Biliary Cholesterol Saturation

3a. Cholesterol Homeostasis and Cholesterol Secretion in Obesity

The Impact of Dietary Cholesterol on Biliary Cholesterol Saturation

De novo Cholesterol Synthesis Is Elevated in Obesity

3b. Endocrine Effects on Cholesterol Supersaturation in Obesity

3c. The Effect of Dietary Factors on Cholesterol Supersaturation

Direct Influence of the Diet on Cholesterol Supersaturation

The Effect of Diet On Overall Cholesterol Homeostasis

4. The Effects of Obesity on Cholesterol Nucleation

5. The Effect on Dietary Factors on Cholesterol Nucleation

5a. Effects of the Diet on Bile Acids

5b. Effects of the Diet on Biliary Fat Content

5c. Effects of the Diet on Biliary Proteins

6. The Effects of Obesity on Gallbladder Function

6a. Resting Gallbladder Volume in Obesity

6b. Gallbladder Motility in Obesity

6c. Mechanism of Gallbladder Dysmotility in Obesity

6d. The Effect of Dietary Factors on Gallbladder Contraction

7. Weight-Loss Strategies: Avoiding Gallstones

7a. How Does Weight Loss Induce a Higher Risk of Gallstone Formation?

7b. Surgical Techniques: Bariatric Surgery

7c. Dietary Components that Can Prevent and Reverse Cholesterol Gallstone Disease during Rapid Weight Loss

Conclusion

References

Role of Insulin Resistance in the Formation of Cholesterol Gallstones

Abstract

1. Introduction

2. Epidemiological Relationships between Insulin Resistance and Gallstones

3. The Metabolic Syndrome and the Central Role of the Liver

4. Insulin Resistance and Pathogenic Factors for Gallstone Formation

4a. Insulin Resistance and Bile Composition

4b. Gallbladder Motility

4c. Intestinal Absorption of Cholesterol

5. Epigenetic Mechanisms Linked with Insulin Resistance and Gallstone Formation

Conclusion

References

Diabetes and Gallstones

Abstract

1. Epidemiological Relationships between Diabetes and Gallstone Disease

2. Type 2 Diabetes and Gallstone Disease: Pathophysiological Links

2a. Insulin Resistance Increases the Risk of Gallstone Occurrence

2b. Influence of Diabetes on the Pathogenesis of Gallstones

Gallbladder Motility in Diabetic Patients

Diabetes and Bile Composition

Diabetes and Gallstones: Common Epigenetic Pathways

3. Gallstone Disease and Type 1 Diabetes

Conclusion

References

Nonalcoholic Fatty Liver Disease and Gallstone Disease

Abstract

Abbreviations

1. Introduction

2. NAFLD

3. Gallstone Disease

4. Association of NAFLD with Cholesterol Gallstone Disease

4.1. Clinical Studies

4.2. Pathophysiological Mechanisms

Conclusion

Acknowledgments

References

Diagnostic Flow Charts for Biliary Lithiasis

Abstract

1. Introduction

2. Types of Gallstones

3. Risk Factors

4. Pathophysiology

5. Gallbladder Stones

5a. Presentation

5b. Diagnosis

6. Bile Duct Stones

6a. Presentation

6b. Diagnosis

7. Complications

7a. Acute Cholangitis

7b. Emphysematous Cholecystitis

7c. Cholecystoenteric Fistula

7d. Mirizzi Syndrome

7e. Gallbladder Cancer

References

Gallbladder Imaging

Abstract

1. Introduction

2. Normal Imaging Anatomy

3. Cholelithliasis

3a. Sonographic Findings

3b. CT Findings

3c. MR Findings

4. Choledocholithiasis

4a. Sonographic Findings

4b. CT Findings

4c. MR Findings

5. Gallbladder Sludge

6. Hemobilia

7. Milk of Calcium Bile

8. Acute Cholecystitis

8a. Sonographic Findings

8b. CT Findings

8c. MRI Findings

9. Acute Acalculous Cholecystitis

10. Complications of Acute Cholecystitis

10a. Empyema

10b. Gangrenous Cholecystitis

10c. Emphysematous Cholecystitis

10d. Gallbladder Perforation

10e. Hemorrhagic Cholecystitis

10f. Xanthogranulomatous Cholecystitis

11. Chronic Cholecystitis

12. Porcelain Gallbladder

13. Gallbladder Adenomyomatosis

13a. Sonographic Findings

13b. MDCT Findings

13c. MR Findings

14. Cholesterolosis and Cholesterol Polyps

15. Gallbladder Carcinoma

15a. Carcinoma Manifesting as Mural Thickening

15b. Carcinoma Manifesting as a Polypoid Mass

15c. Carcinoma Manifesting as a Gallbladder Fossa Mass

Conclusion

References

Current Pharmacological Therapy in Cholesterol Gallstones

Abstract

Abbreviations

1. Introduction

2. The Natural History of Gallstone Disease

3. Identification of Symptomatic Patients as Candidate to Treatments

4. Therapeutic Approaches to Gallstones

4.1. Elective Cholecystectomy

4.2. Oral Litholysis

4.3. Non-Bile Acid Medical Treatment of Cholesterol Gallstones

5. Prevention of Cholesterol Gallstones by Medical Treatment

Conclusion

Acknowledgments

References

Laparoscopic Cholecystectomy

Abstract

Abbreviations

1. Introduction

2. Indications

3. Contraindications

4. Technique

5. Conversion to Laparotomy

6. Complications

7. Laparoscopic Cholecystectomy and Incidental Gallbladder Cancer

Conclusion

References

Surgical Treatment of Common Bile Duct Stones

Abstract

1. Introduction

2. Surgical CBD Exploration – Approaches

2a. Laparoscopic CBD Exploration – Technique

Instrumentation

Positioning of the Patient

Trocar Placement

Exposure and Dissection

Intraoperative Cholangiography

Approach

(i) Transcystic Approach

(ii) Transductal Approach

Lithotripsy

Completion Cholangiography

Postoperative Care

Contraindications

2b. Open CBD Exploration – Technique

3. Surgical CBD Exploration – Failure and Complications

3a. Failure to Clear the CBD

3b. Complications

Bile Leakage

CBD Injury

Postoperative Pancreatitis

Abscess

Wound Infection

Complications Related to Cholecystectomy

4. Choledocholithiasis - Endoscopic and Surgical Management

4a. Open CBD Exploration versus ERCP

4b. Open CBD Exploration versus Laparoscopic CBD Exploration

5. Combined Choledochocystolithiasis - Endoscopic and Surgical Management

5a. Two-Stage Approach

Preoperative ERCP with Laparoscopic Cholecystectomy

Laparoscopic Cholecystectomy with Postoperative ERCP

5b. Single-Stage Approach

Laparoscopic Cholecystectomy with Laparoscopic Common BileDuct Exploration

Laparoscopic Cholecystectomy with Intraoperative ERCP

Conclusion

References

Recent Progress in the Diagnosis and Treatment of Gallstones

Abstract

1. Introduction

2. Epidemiology

3. Pathogenesis and Risk Factors

3a. Cholesterol Gallstones

3b. Brown Pigment Gallstones

3c. Black Pigment Gallstones

4. Investigations

4a. Ultrasonography (USG)

4b. Computed Tomography (CT) Scan

4c. Magnetic Resonance Cholangiopancreatography (MRCP)

4d. Endoscopic Ultrasound (EUS)

4e. Endoscopic Retrograde Cholangiopancreatography (ERCP)

4f. Hepatobiliary Iminodiacetic Acid (HIDA) Scan

5. Management

5a. Asymptomatic Gallstones

5b. Symptomatic Patients without Complications

5c. Acute Cholecystitis

5d. Obstructive Jaundice

5e. Acute Cholangitis

5f. Acute Pancreatitis

5g. Mirizzi Syndrome

5h. Gallstone Ileus

5i. Gallbladder Cancer

Conclusion

References

Endoscopic Management of Biliary Ductal Stones

Abstract

Abbreviations

1. Introduction

2. Diagnosis

3. Treatment

3a. Surgery

3b. Preoperative ERCP (Before Laparoscopic Cholecystectomy)

3c. Postoperative ERCP (Post Laparoscopic Cholecystectomy)

3d. Intraoperative ERCP (during a Laparoscopic Cholecystectomy)

3e. Laparoscopic Cholecystectomy with Concomitant Exploration of Common Bile Duct

4. ERCP

4a. Preparation

4b. ERCP Technique

4c. Difficult Lithiasis of the Main Biliary Tract

4d. Role of the Pre-Cut Papillotomy

4e. ERCP-Related Complications

4f. Post-ERCP Pancreatitis

4g. Antibiotic Prophylaxis

4h. Sedation

5. CBDS in the Elderly Patient

6. CBDS and Pregnancy

Acknowledgments

References

Hepatolithiasis: Progress in Diagnosis and Surgical Treatment

Abstract

1. Introduction

2. Japanese Multicenter Survey

3. Diagnostic Tools

4. Surgical Treatment

Conclusion

References

Recent Progress on the Endoscopic Treatment of Bile Duct Stones with Endoscopic Papillary Large Balloon Dilation

Abstract

1. Introduction

2. Indications for EPLBD

3. EPLBD Methods

4. Stone Removal Rates with EPLBD

5. Causes of Failure in Stone Removal with EPLBD

6. Alternatives to EML

7. Early Complications of EPLBD

8. Cholangitis

9. Pancreatitis

10. Bleeding

11. Perforation

12. Follow-Up Studies

13. Management of Recurrent Bile Duct Stones after Prior EST

14. EPLBD for Patients with Billroth II and Roux-En-Y Reconstruction

Conclusion

Acknowledgments

References

Surgical Treatment of Gallstones and Their Complications

Abstract

1. Introduction

2. Management of Gallbladder Stones

2a. Asymptomatic Gallstones

2b. Symptomatic Gallstones

3. Methods of Cholecystectomy

3a. Laparoscopic Versus Open Cholecystectomy

3b. Peri-Operative Interventions Related to Cholecystectomy

3c. Number of Ports and Size of Ports

3d. Timing of Laparoscopic Cholecystectomy

3e. Complications of Laparoscopic Cholecystectomy

3f. Patients at High Surgical Risk

4. Quality of Life After Treatment for Gallstones

Conclusion

References

Treatment of Intrahepatic Duct Stones: A Western Perspective

Abstract

Abbreviations

1. Introduction

2. Definition and Classification

3. Pathology

4. Clinical Presentation

5. Diagnosis

5a. Ultrasonography

5b. Computed Tomography

5c. Magnetic Resonance

6. Cholangiocarcinoma

7. Therapy

7a. Surgical Treatment

7b. Non-Surgical Treatment

References

Mirizzi Syndrome

Abstract

Abbreviations

1. Introduction

2. History of Mirizzi Syndrome

3. Pathophysiology and classifications of Mirizzi syndrome

4. Prevalence of Mirizzi syndrome

5. Diagnosis

6. Treatment

6a. Mirizzi Syndrome without Cholecystobiliary Fistula

6b. Mirizzi Syndrome with Cholecystobiliary Fistula

6c. Non-Surgical Treatment of Mirizzi Syndrome

6d. Mirizzi Syndrome with Gallbladder Carcinoma

6e. Development in Laparoscopic Treatment

6f. Postoperative Morbidity and Mortality Rates

Conclusion

Acknowledgments

References

About the Editors

Index