Practical Gastroenterology and Hepatology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1225

Veröffentlichungsjahr: 2011

Beschreibung

This comprehensive resource for fellows/trainees and candidates for recertification in gastroenterology summarizes the field in a modern, fresh format. Prominent experts from around the globe write on their areas of expertise, and each chapter follows a uniform structure. The focus is on key knowledge, with the most important clinical facts highlighted in boxes. Color illustrations reinforce the text.

Leseprobe

Contents

Contributors

Preface

Foreword

Part 1: Pathobiology of the Intestine and Pancreas

1 Clinical Anatomy, Embryology, and Congenital Anomalies,Advitya Malhotra and Joseph H. Sellin

Small and Large Intestine

Pancreas

References

2 Physiology of Weight Regulation,Louis Chaptini, Christopher Deitch, and Steven Peikin

Introduction

Concept of Energy Homeostasis

Role of the Central Nervous System

Role of Adipose Tissue

Role of the Gastrointestinal Tract

Conclusion

References

3 Small Intestinal Hormones and Neurotransmitters,Nithin Karanth and James C. Reynolds

Introduction

Characteristics of Gastrointestinal Hormones

Neuroendocrine Tumors

Endocrine Peptides

References

4 Mucosal Immunology of the Intestine,Steven J. Esses and Lloyd Mayer

Introduction

Mucosal and Epithelial Barrier

Innate Immune System

Antigen Uptake and Induction of a Mucosal Immune Response

Adaptive Immune System

Humoral Response and Secretory I g A

Tolerance and Regulatory T Cells

Commensal Flora

References

5 Motor and Sensory Function,Eamonn M.M. Quigley

Introduction

Gut Muscle and Nerve

Gut Sensation

The Autonomic Nervous System

The “Big” Brain and Gut Function

Small Intestinal Motor Activity

Colonic Motility

Motor Activity of the Anorectum

Small Intestinal, Colonic, and Anorectal Sensation

References

6 Neoplasia,John M. Carethers

Definition and Epidemiology

Clinical Features

Pathophysiology

Diagnosis

Treatment

References

Part 2: Colonoscopy, Endoscopic Retrograde Cholangiopancreato graphy, and Endoscopic Ultrasound

7 Technique of Colonoscopy,Anna M. Buchner and Michael B. Wallace

Introduction

Basic Techniques

Colonoscopy Imaging Technologies

Conclusions

References

8 Advanced Colonoscopy, Polypectomy, and Colonoscopic Imaging,Douglas K. Rex

Insertion Techniques in Difficult Colons

Advanced Techniques for Polyp Resection

Endoscopic Imaging in the Colon

Determination of Histology in Real Time

References

9 Complications of Colonoscopy,Ana Ignjatovic and Brian Saunders

Introduction

Precolonoscopy

Bowel Preparation

Intubation

Extubation

Conclusion

References

10 Pancreatography (Including Pancreatic Sphincterotomy and Difficult Cannulation),Nalini M. Guda and Martin L. Freeman

Anatomical/Embryological Considerations

Pancreatic Duct Cannulation and Sphincterotomy

Pancreas Divisum and Minor Papilla Interventions

Pancreatography, Endoscopic, and Other Methods for Chronic Pancreatitis

Pancreatoscopy

References

11 Endoscopic Ultrasound,David J. Owens and Thomas J. Savides

Introduction

Small Bowel EUS

Colorectal EUS

Complications of EUS

References

Part 3: Other Investigations of the Intestine and Pancreas

12 Capsule Endoscopy,Blair S. Lewis

Introduction

Contraindications

References

13 Enteroscopy,G. Anton Decker and Jonathan A. Leighton

Equipment and Review of Technology

How to Perform Double Balloon Enteroscopy (Video 11)

Diagnostic and Therapeutic Methods

Diagnostic Yield

Comparison to Other Imaging Modalities of the Small Bowel

Therapeutic Role

Complications

References

14 Other Investigations of the Intestine and Pancreas: Diagnostic Imaging,Saravanan Krishnamoorthy, Bobby Kalb, Sonali Sakaria, Shanthi V. Sitaraman, and Diego R. Martin

Intestine

Pancreas

Conclusions

References

15 Motility Testing of the Intestine,Eamonn M.M. Quigley

Introduction

Equipment, Review of Technology, and Indications

Techniques

Interpretation

Role and Therapeutic Implications Small Intestine

Complications

References

16 Pancreatic Function Testing,John G. Lieb II and Christopher E. Forsmark

Normal Pancreatic Function and Principles of Pancreatic Function Testing

Direct Pancreatic Function Tests

Indirect Pancreatic Function Tests

Utilizing Pancreatic Function Tests

Conclusions

References

Part 4: Problem-based Approach to Diagnosis and Differential Diagnosis

17 General Approach to Relevant History Taking and Physical Examination,Sheryl A. Serbowicz and Suzanne Rose

Introduction to History Taking

Patient Concern—Abdominal Pain

Patient Concern—Bowel Complaints

Patient Concern—Nausea and Vomiting

Patient Concern—Gastrointestinal Bleeding

Patient Concern—Jaundice

Patient Concern—Other Symptoms

Perform a Full Review of Systems/Symptoms

Physical Examination

Conclusions

References

18 Acute Abdominal Pain,Robert M. Penner and Sumit R. Majumdar

Definition

Clinical Features

Investigation

References

19 Acute Diarrhea,John R. Cangemi

Definition and Epidemiology

History and Physical Examination

Differential Diagnosis

Diagnostic Evaluation

Treatment

References

20 Chronic Diarrhea,Lawrence R. Schiller

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis and Differential Diagnosis

Therapeutics

Prognosis

References

21 Loss of Appetite and Loss of Weight,Ronald L. Stone, Kanwar Rupinder S. Gill, and James S. Scolapio

Introduction

History and Physical Exam

Causes of Unintentional Weight Loss

Evaluation of Unintentional Weight Loss

Nutrition Management of Unintentional Weight Loss

References

22 Gastrointestinal Food Allergy and Intolerance,Sheila E. Crowe

Overview of Food Allergy (Hypersensitivity) and Food Intolerances

Immune-mediated Gastrointestinal Adverse Reactions to Food

Non-immune Gastrointestinal Adverse Reactions to Food

Evaluation for GI Food Allergy and Intolerances

Management of Adverse Reactions to Foods

References

23 Abdominal Bloating and Visible Distension,Laura Hwang and Mark Pimentel

Introduction

Definitions of Gas, Bloating, and Distension

Pathophysiology

Relationship to Functional GI Disorders

Diagnostic Evaluation for Gas and Bloating Patients (Table 23.2)

Treatment

Conclusion

References

24 Obesity and Presentations after Anti-obesity Surgery,Patrick Gatmaitan, Stacy A. Brethauer, and Philip R. Schauer

Introduction

Management Options

Complications of Laparoscopic Gastric Bypass

Complications of Laparoscopic Adjustable Gastric Banding

Mortality Risk

Weight Loss

Resolution of Co-morbidities

Mortality Reduction

Conclusion

References

25 Assessment of Nutritional Status,English F. Barbour and Mark DeLegge

Definition and Epidemiology

Pathophysiology

Clinical Features

Therapeutics

Conclusion

References

26 Hematochezia,Lisa L. Strate

Definition and Epidemiology

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

27 Obscure Gastrointestinal Bleeding,Lisa L. Strate

Definition and Epidemiology.

Clinical Features.

Diagnosis

Differential Diagnosis

Therapy

Prognosis

References

28 Constipation,Erica N. Roberson and Arnold Wald

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis.

Therapy

Prognosis

References

29 Perianal Disease,David A. Schwartz and Brad E. Maltz

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Therapeutics

References

30 Fecal Incontinence,Adil E. Bharucha and Karthik Ravi

Introduction

Pathophysiology of Fecal Incontinence

Clinical Features

Diagnostic Testing

Management

Conclusions

References

31 Colorectal Cancer Screening,Katherine S. Garman and Dawn Provenzale

Introduction

Review of Screening Methods

Discussion of the Guidelines

Conclusion

References

32 Endoscopic Palliation of Malignant Obstruction,Todd H. Baron

Equipment and Review of Technology

How to Place Self-expanding Metallic Stents

Malignant Dysphagia

Malignant Gastric Outlet Obstruction

Colonic Obstruction

Enteral Tubes

References

Part 5: Diseases of the Small Intestine

33 Crohn Disease,Faten N. Aberra and Gary R. Lichtenstein

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Disease Activity Indices

Therapeutics

References

34 Small Bowel Tumors,Nadir Arber and Menachem Moshkowitz

Introduction

Benign Tumors of the Small Intestine

Malignant Small Bowel Tumors

Clinical Features (Table 34.1 )

Diagnosis

Therapy

References

35 Small Intestinal Bacterial Overgrowth,Monthira Maneerattanaporn and William D. Chey

Definition and Epidemiology

Pathophysiology

Clinical Manifestation

Diagnosis

Treatment

References

36 Celiac Disease and Tropical Sprue,Alberto Rubio-Tapia and Joseph A. Murray

Celiac Disease

Tropical Sprue

References

37 Whipple Disease,George T. Fantry

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

38 Short Bowel Syndrome,David M. Shapiro and Alan L. Buchman

Definition and Epidemiology

Pathophysiology

Clinical Features

Differential Diagnosis

Therapeutics

Prognosis

References

39 Protein-losing Gastroenteropathy,Lauren K. Schwartz and Carol E. Semrad

Definition

Pathophysiology

Etiologies

Clinical Features

Diagnosis

Therapy

Monitoring

References

40 Acute Mesenteric Ischemia and Chronic Mesenteric Insufficiency,Timothy T. Nostrant

Acute/Chronic Mesenteric Ischemia

Vascular Anatomy/Function Mesenteric Circulation

Mesenteric Vascular Physiology

Acute Mesenteric Ischemia

Chronic Mesenteric Insufficiency

References

41 Small Intestinal Ulceration,Reza Y. Akhtar and Blair S. Lewis

Introduction

Capsule Endoscopy

References

42 Intestinal Obstruction and Pseudo-obstruction,Charlene M. Prather

Introduction

Intestinal Obstruction

Intestinal Pseudo - obstruction

Conclusion

References

Part 6: Diseases of the Colon and Rectum

43 Ulcerative Colitis,Timothy L. Zisman and Stephen B. Hanauer

Definition

Epidemiology

Risk Factors

Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

References

44 Infectious Proctocolitis,Disaya Chavalitdhamrong, Gary C. Chen, and Rome Jutabha

Introduction and Approach to the Patient

Colitis

Proctocolitis

Proctitis

References

45 Microscopic Colitis,Darrell S. Pardi

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

46 Colonic Ischemia,Timothy T. Nostrant

Epidemiology

Pathophysiology

Pharmacologic-induced Colon Injury

Clinical Manifestations

Therapy of Colonic Ischemia

References

47 Acute Diverticulitis,Chee-Chee H. Stucky and Tonia M. Young-Fadok

Definition and Epidemiology

Clinical Features

Diagnosis

Treatment

References

48 Acute Colonic Pseudo-obstruction,Michael D. Saunders

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Prognosis

Chronic Colonic Pseudo-obstruction

Therapeutics

References

49 Colonic Polyps and Colon Cancer,John B. Kisiel and Paul J. Limburg

Definition and Epidemiology

Pathophysiology

Prevention

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

50 Clostridium difficile Infection and Pseudomembranous Colitis,Alan C. Moss and John Thomas LaMont

Definition and Epidemiology

Pathophysiology

Clinical Features of GdifficileInfection

Diagnosis

Differential Diagnosis

Treatment

Prognosis

References

51 Anorectal Testing,Karthik Ravi and Adil E. Bharucha

Tests of Function

Tests of Structure

Tests of Structure and Function

Conclusions

Acknowledgments

References

52 Abdominal Abscesses and Gastrointestinal Fistula,Faten N. Aberra and Gary R. Lichtenstein

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Therapeutics

References

53 Acute Appendicitis,Patricia Sylla and Richard Hodin

Definition and Epidemiology

Anatomy and Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis

Management

Complications

References

54 Pregnancy and Luminal Gastrointestinal Disease,Nielsen Q. Fernandez-Becker and Jacqueline L. Wolf

Esophagus and Stomach

Small Intestine and Large Bowel

Conclusions

References

55 Consequences of Human Immunodeficiency Virus (HIV) Infection,Vera P. Luther and P. Samuel Pegram

Definition and Epidemiology

Pathogenesis

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

Part 7: Diseases of the Pancreas

56 Acute Pancreatitis and Peripancreatic Fluid Collections,Peter A. Banks and Koenraad J. Mortele

Introduction

Definitions

Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Therapeutics (Table 56.2 and Figure 56.7 )

Prognosis

References

57 Chronic Pancreatitis and Pancreatic Pseudocysts,Nison Badalov and Scott Tenner

Chronic Pancreatitis

Pseudocysts — Natural History

Diagnosis

Symptoms

Drainage of Pseudocysts

Medical Therapy

Surgical Drainage

Radiologic (Percutaneous) Drainage

Endoscopic Drainage

References

58 Pancreatic Cancer and Cystic Pancreatic Neoplasms,Field F. Willingham and William R. Brugge

Pancreatic Cancer

Cystic Pancreatic Neoplasms

References

59 Palliation of Malignant Biliary Obstruction,Yan Zhong and Nib Soehendra

Introduction

Stenting of Distal CBD Obstructions

Duodenal Stenting

Pancreatic Duct Stenting

References

Part 8: Functional Gastrointestinal Disorders

60 Irritable Bowel Syndrome,Elizabeth J. Videlock and Lin Chang

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Management

References

61 Functional Constipation and Pelvic Floor Dysfunction,Ernest P. Bouras

Definition and Epidemiology

Pathophysiology

Clinical Features

Diagnosis

Therapeutics

References

62 Chronic Functional Abdominal Pain,Samantha A. Scanlon, Madhusudan Grover, Amy E. Foxx-Orenstein, and Douglas A. Drossman

Definition

Epidemiology and Health Care Impact

Pathophysiology

Clinical Features

Diagnosis

Differential Diagnosis

Therapeutics

Prognosis

References

63 Functional Abdominal Bloating and Gas,Fernando Azpiroz

Definition and Epidemiology

Pathophysiology and Clinical Features

Diagnosis and Differential Diagnosis

Therapeutics

Prognosis

References

Part 9: Transplantation

64 Small Bowel Transplantation,Juan P. Rocca and Jonathan P. Fryer

Introduction and Definitions

Indications: When to Refer for Intestinal Transplant

Indications: Types of Intestinal Transplant

Outcomes

Conclusion

References

65 Gastrointestinal Complications of Solid Organ and Hematopoietic Cell Transplantation,Natasha Chandok and Kymberly D.S. Watt

Introduction

Infections in the GI System Following SOT or HCT

GI Malignancies after SOT and HCT

Gastrointestinal Adverse Drug Events

General GI Complications

Special Topics

References

Part 10: Peritoneal and Other Abdominal Disease

66 Peritonitis,Robert R. Cima

Anatomy and Definitions

Pathophysiology

Clinical Syndrome

Conclusions

References

67 Abdominal Hernia,Michael Cox

Definitions and Epidemiology

Clinical Features

Clinical Signs

Investigations

Treatment

References

Index

A companion website for this book is available at: practicalgastrohep.com

Companion website

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practicalgastrohep.com

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Contributors

Faten N. Aberra, MD, MSCEAssistant Professor of MedicineDivision of GastroenterologyHospital of the University of PennsylvaniaPhiladelphia, PA, USA

Reza Y. Akhtar, MDFellow in GastroenterologyHenry D. Janowitz Division of GastroenterologyMount Sinai School of MedicineNew York, NY, USA

Nadir Arber, MD, MSc, MHAProfessor of Medicine and GastroenterologyYechiel and Helen Lieber Professor for Cancer ResearchHead of The Integrated Cancer Prevention CenterTel-Aviv Sourasky Medical CenterSackler Faculty of MedicineTel-Aviv UniversityTel Aviv, Israel

Fernando Azpiroz, MDProfessor of MedicineChair, Department of GastroenterologyUniversity Hospital Vall d’Hebron Barcelona, Spain

Nison Badalov, MDAssistant DirectorBrooklyn Gastroenterology and Endoscopy AssociatesMaimonides Medical CenterState University of New York — Health Sciences CenterNew York, NY, USA

Peter A. Banks, MDProfessor of MedicineDivision of GastroenterologyCenter for Pancreatic DiseaseHarvard Medical SchoolBrigham and Women ’s HospitalBoston, MA, USA

English F. Barbour, RD, LD, CNSDDietitianDigestive Disease CenterMedical University of South CarolinaCharleston, SC, USA

Todd H. Baron, MDProfessor of MedicineDivision of Gastroenterology and HepatologyDirector of Pancreaticobiliary EndoscopyMayo ClinicRochester, MN, USA

Adil E. Bharucha, MBBS, MDProfessor of MedicineClinical Enteric Neuroscience Translational andEpidemiological Research ProgramDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Ernest P. Bouras, MDAssistant Professor of MedicineDivision of Gastroenterology and HepatologyMayo ClinicJacksonville, FL, USA

Stacy A. Brethauer, MDStaff SurgeonBariatric and Metabolic InstituteCleveland ClinicCleveland, OH, USA

William R. Brugge, MDDirector, Gastrointestinal EndoscopyGastrointestinal UnitMassachusetts General HospitalProfessor of MedicineHarvard Medical SchoolBoston, MA, USA

Alan L. Buchman, MD, MSPHProfessor of Medicine and SurgeryDivision of GastroenterologyFeinberg School of MedicineNorthwestern UniversityChicago, IL, USA

Anna M. Buchner, MD, PhDInstructor of MedicineFellow in Advanced EndoscopyDepartment of GastroenterologyUniversity of PennsylvaniaPhiladelphia, PA, USA

John R. Cangemi, MDAssistant ProfessorDivision of Gastroenterology and HepatologyDepartment of Internal MedicineMayo ClinicJacksonville, FL, USA

John M. Carethers, MDJohn G. Searle Professor and ChairDepartment of Internal MedicineUniversity of MichiganAnn Arbor, MI, USA

Natasha Chandok, MDInstructor of MedicineDivision of Gastroenterology and HepatologyUniversity of Western OntarioLondon, ON, Canada

Lin Chang, MDProfessor of MedicineCenter for Neurobiology of StressDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLAVA Greater Los Angeles Healthcare SystemLos Angeles, CA, USA

Louis Chaptini, MDAssistant Professor of MedicineDivision of Gastroenterology and Liver DiseasesCooper University HospitalRobert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyCamden, NJ, USA

Disaya Chavalitdhamrong, MDResearch FellowDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos Angeles, CA, USA

Gary C. Chen, MDClinical FellowDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos Angeles, CA, USA

William D. Chey, MDProfessor of MedicineDirector, GI Physiology LaboratoryUniversity of MichiganHealth SystemAnn Arbor, MI, USA

Robert R. Cima, MD, MAAssociate Professor of SurgeryDepartment of SurgeryMayo ClinicRochester, MN, USA

Michael Cox, MB BS, MSProfessor of SurgeryDepartment of SurgeryUniversity of SydneyNepean HospitalPenrith, NSW, Australia

Sheila E. Crowe, MDProfessor of MedicineDivision of Gastroenterology and HepatologyDepartment of MedicineUniversity of VirginiaCharlottesville, VA, USA

G. Anton Decker, MB BCh, MRCPAssociate Professor of MedicineDirector of the Pancreas ClinicDivision of GastroenterologyMayo ClinicScottsdale, AZ, USA

Christopher Deitch, MDAssistant Professor of MedicineDivision of Gastroenterology and Liver DiseasesCooper University HospitalRobert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyCamden, NJ, USA

Mark DeLegge, MDProfessor of MedicineDirector, Digestive Disease CenterMedical University of South CarolinaCharleston, SC, USA

Douglas A. Drossman, MDCo-Director, UNC Center for Functional GI andMotility DisordersDivision of Gastroenterology and HepatologyUniversity of North CarolinaChapel Hill, NC, USA

Steven J. Esses, BAResearch FellowDivision of GastroenterologyMount Sinai School of MedicineNew York, NY, USA

George T. Fantry, MDAssociate Professor of MedicineDirector, Heartburn and Dyspepsia ProgramDivision of GastroenterologyUniversity of Maryland School of MedicineBaltimore, MD, USA

Nielsen Q. Fernandez-Becker,MD, PhDInstructor of MedicineDivision of Gastroenterology and HepatologyStanford University School of MedicineStanford, CA, USA

Christopher E. Forsmark, MDProfessor of MedicineChief, Division of Gastroenterology, Hepatology, and NutritionUniversity of FloridaGainesville, FL, USA

Amy E. Foxx-Orenstein, DOAssociate Professor of MedicineDivision of Gastroenterology and HepatologyMiles and Shirley Fiterman Center for Digestive DiseasesMayo ClinicRochester, MN, USA

Martin L. Freeman, MDProfessor of MedicineInterim Director, Division of Gastroenterology, Hepatologyand NutritionDirector, Pancreaticobiliary Endoscopy FellowshipCodirector, Minnesota Pancreas and Liver CenterUniversity of MinnesotaMinneapolis, MN, USA

Jonathan P. Fryer, MDAssociate Professor of SurgeryDivision of TransplantationDepartment of SurgeryFeinberg School of MedicineNorthwestern UniversityChicago, IL, USA

Katherine S. Garman, MDAssistant Professor of MedicineDivision of Gastroenterology and Institute for GenomeSciences and PolicyVeterans Affairs Medical CenterDuke UniversityDurham, NC, USA

Patrick Gatmaitan, MDFellow in Advanced Laparoscopic and Bariatric SurgeryBariatric and Metabolic InstituteCleveland ClinicCleveland, OH, USA

Kanwar Rupinder S. Gill, MDStaff GastroenterologistDepartment of GastroenterologySutter Gould Medical FoundationModesto, CA, USA

Madhusudan Grover, MDFellow in GastroenterologyDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Nalini M. Guda, MDClinical Associate Professor of MedicineUniversity of Wisconsin School of Medicine and Public HealthPancreatobiliary ServicesSt. Luke’s Medical CenterMilwaukee, WI, USA

Stephen B. Hanauer, MDProfessor of Medicine and Clinical PharmacologyChief, Section of Gastroenterology, Hepatology and NutritionUniversity of Chicago Medical CenterChicago, IL, USA

Richard Hodin, MDProfessor of SurgeryDepartment of SurgeryHarvard Medical SchoolMassachusetts General HospitalBoston, MA, USA

Laura Hwang, BAMedical StudentGI Motility ProgramCedars-Sinai Medical CenterLos Angeles, CA, USA

Ana Ignjatovic, BA, BMBCh, MRCPResearch Fellow in EndoscopyWolfson Unit for EndoscopySt Mark’s HospitalHarrow, UK

Rome Jutabha, MDAssociate Professor of MedicineDirector, UCLA Center for Small Bowel DiseasesDivision of Digestive DiseasesDavid Geffen School of Medicine at UCLALos Angeles, CA, USA

Bobby Kalb, MDAssistant ProfessorBody MRI Applied Research ProgramDepartment of RadiologyEmory University School of MedicineAtlanta, GA, USA

Nithin Karanth, MDFellow in GastroenterologyDepartment of GastroenterologyDrexel University College of MedicinePhiladelphia, PA, USA

John B. Kisiel, MDInstructor of MedicineDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Saravanan Krishnamoorthy, MDAssistant ProfessorDepartment of Diagnostic RadiologyYale UniversityNew Haven, CT, USA

John Thomas LaMont, MDChief of GastroenterologyDivision of GastroenterologyBeth Israel Deaconess Medical CenterProfessor of MedicineHarvard Medical SchoolBoston, MA, USA

Jonathan A. Leighton, MDProfessor of MedicineChair, Division of GastroenterologyMayo ClinicScottsdale, AZ, USA

Blair S. Lewis, MDClinical Professor of MedicineHenry D. Janowitz Division of GastroenterologyMount Sinai School of MedicineNew York, NY, USA

Gary R. Lichtenstein, MDProfessor of MedicineDivision of GastroenterologyHospital of the University of PennsylvaniaPhiladelphia, PA, USA

John G. Lieb II, MDInstructor of MedicineDivision of GastroenterologyUniversity of PennsylvaniaPhiladelphia, PA, USA

Paul J. Limburg, MD, MPHProfessor of MedicineDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Vera P. Luther, MDAssistant Professor of MedicineSection on Infectious DiseasesDepartment of Internal MedicineWake Forest University School of MedicineWinston-Salem, NC, USA

Sumit R. Majumdar, MD, MPHAssociate ProfessorDepartment of MedicineUniversity of AlbertaEdmonton, AB, Canada

Advitya Malhotra, MD, MSFellow in GastroenterologyDepartment of Gastroenterology and HepatologyUniversity of Texas Medical Branch (UTMB)Galveston, TX, USA

Brad E. Maltz, MDFellow in GastroenterologyDivision of GastroenterologyVanderbilt UniversityNashville, TN, USA

Monthira Maneerattanaporn, MDResearch Fellow in GastroenterologyUniversity of MichiganAnn Arbor, MI, USA;Clinical Lecturer, Department of MedicineSiriraj HospitalMahidol UniversityBangkok, Thailand

Diego R. Martin, MD, PhDProfessor of RadiologyDepartment of RadiologyEmory University School of MedicineAtlanta, GA, USA

Lloyd Mayer, MDProfessor of Immunology and MedicineDivisions of Clinical Immunology and GastroenterologyMount Sinai Medical CenterNew York, NY, USA

Koenraad J. Mortele, MDAssociate Professor of RadiologyHarvard Medical School;Associate Director, Division of Abdominal Imaging andInterventionDirector of Abdminal and Pelvic MRIDepartment of RadiologyBrigham and Women ’s HospitalBoston, MA, USA

Menachem Moshkowitz, MDAssistant Professor of MedicineIntegrated Cancer Prevention CenterTel-Aviv Sourasky Medical CenterSackler Faculty of MedicineTel-Aviv UniversityTel-Aviv, Israel

Alan C. Moss, MDAssistant Professor of MedicineHarvard Medical SchoolDirector of Translational ResearchCenter for Inflammatory Bowel DiseaseDivision of GastroenterologyBeth Israel Deaconess Medical CenterBoston, MA, USA

Joseph A. Murray, MDProfessor of Medicine and ImmunologyDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Timothy T. Nostrant, MDProfessor of MedicineDepartment of Internal MedicineUniversity of MichiganAnn Arbor, MI, USA

David J. Owens, MDClinical InstructorDivision of GastroenterologyUniversity of California, San DiegoSan Diego, CA, USA

Darrell S. Pardi, MDAssociate Professor of MedicineInflammatory Bowel Disease ClinicDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

P. Samuel Pegram, MDProfessor of Medicine with TenureDepartment of Internal MedicineWake Forest University School of MedicineWinston-Salem, NC, USA

Steven Peikin, MDProfessor of MedicineDivision of Gastroenterology and Liver DiseasesCooper University HospitalRobert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyCamden, NJ, USA

Robert M. Penner, MD, MScAssistant Clinical ProfessorDepartment of MedicineUniversity of AlbertaEdmonton, AB, Canada;Department of MedicineUniversity of British ColumbiaVancouver, BC, Canada

Mark Pimentel, MDDirector, GI Motility ProgramCedars-Sinai Medical CenterLos Angeles, CA, USA

Charlene M. Prather, MD, MPHAssociate Professor of Internal MedicineProgram Director, Gastroenterology Fellowship ProgramDepartment of MedicineSaint Louis University School of MedicineSt. Louis, MO, USA

Dawn Provenzale, MD, MSProfessor of MedicineVeterans Affairs Medical CenterDivision of GastroenterologyDuke University Medical CenterDurham, NC, USA

Eamonn M.M. Quigley, MDProfessor of Medicine and Human PhysiologyDepartment of MedicineAlimentary Pharmabiotic CentreUniversity College CorkCork, Ireland

Karthik Ravi, MDFellowClinical Enteric Neuroscience Translational andEpidemiological Research ProgramDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Douglas K. Rex, MDDistinguished Professor of MedicineIndiana University School of MedicineDirector of EndoscopyIndiana University HospitalIndianapolis, IN, USA

James C. Reynolds, MDJune F. Klinghoffer Distinguished ProfessorChair, Department of MedicineDrexel University College of MedicinePhiladelphia, PA, USA

Erica N. Roberson, MDFellow in Women’s Health—Women’s Veteran Health ProgramInstructor in MedicineSection of Gastroenterology and HepatologyUniversity of Wisconsin School of Medicine and Public HealthMadison, WI, USA

Juan P. Rocca, MDAssistant Professor of SurgeryMount Sinai School of MedicineTransplant SurgeonRecanati/Miller Transplant InstituteNew York, NY, USA

Suzanne Rose, MD, MSEdProfessor of Medical Education and MedicineAssociate Dean for Academic and Student AffairsAssociate Dean for Continuing Medical EducationDepartment of Medical Education and Department ofMedicineDivision of GastroenterologyMount Sinai School of MedicineNew York, NY, USA

Alberto Rubio-Tapia, MDAssistant Professor of MedicineDivision of Gastroenterology and HepatologyMayo ClinicRochester, MN, USA

Sonali Sakaria, MDFellowDepartment of MedicineDivision of Digestive DiseasesEmory University School of MedicineAtlanta, GA, USA

Brian Saunders MD, FRCPConsultant GastroenterologistReader in EndoscopyImperial College LondonDirector of Wolfson Unit for EndoscopySt Mark’s HospitalHarrow, UK

Michael D. Saunders, MDClinical Associate Professor of MedicineDivision of GastroenterologyDirector of Digestive Disease CenterUniversity of Washington Medical CenterSeattle, WA, USA

Thomas J. Savides, MDProfessor of Clinical MedicineDivision of GastroenterologyUniversity of California, San DiegoSan Diego, CA, USA

Samantha A. Scanlon, MDMedical ResidentDepartment of Internal MedicineMayo ClinicRochester, MN, USA

Philip R. Schauer, MDDirector, Bariatric and Metabolic InstituteCleveland ClinicCleveland, OH, USA

Lawrence R. Schiller, MDProgram Director, Gastroenterology FellowshipDivision of GastroenterologyBaylor University Medical CenterDallas, TX, USA

David A. Schwartz, MDAssociate Professor of MedicineDirector, IBD CenterDivision of GastroenterologyVanderbilt UniversityNashville, TN, USA

Lauren K. Schwartz, MDAssistant Professor of MedicineDivision of GastroenterologyMount Sinai HospitalNew York, NY, USA

James S. Scolapio, MDProfessor of MedicineDirector of NutritionDivision of Gastroenterology and HepatologyMayo ClinicJacksonville, FL, USA

Joseph H. Sellin, MDProfessor of MedicineDivision of GastroenterologyBaylor College of MedicineHouston, TX, USA

Carol E. Semrad, MDAssociate Professor of MedicineGastroenterology SectionThe University of ChicagoChicago, IL, USA

Sheryl A. SerbowiczMedical StudentDepartment of Medical EducationMount Sinai School of MedicineNew York, NY, USA

David M. Shapiro, MDFellow in Gastroenterology and HepatologyDivision of GastroenterologyFeinberg School of MedicineNorthwestern UniversityChicago, IL, USA

Shanthi V. Sitaraman, MD, PhDProfessorDepartment of MedicineDivision of Digestive DiseasesEmory University School of MedicineAtlanta, GA, USA

Nib Soehendra, MDEndoscopy Practice am GlockengiesserwallHamburg, Germany

Ronald L. Stone, RDAssistant Professor of NutritionDepartment of DieteticsMayo ClinicJacksonville, FL, USA

Lisa L. Strate, MD, MPHAssistant Professor of MedicineDivision of GastroenterologyUniversity of Washington School of MedicineHarborview Medical CenterSeattle, WA, USA

Chee-Chee H. Stucky, MDResident, General Surgery Residency ProgramDepartment of General SurgeryMayo ClinicScottsdale, AZ, USA

Patricia Sylla, MDInstructor in SurgeryHarvard Medical SchoolAssistant in SurgeryDivision of Colorectal SurgeryDepartment of SurgeryMassachusetts General HospitalBoston, MA, USA

Scott Tenner, MD, MPHAssociate Professor of MedicineDivision of GastroenterologyDepartment of MedicineMaimonides Medical CenterState University of New York—Health Sciences CenterNew York, NY, USA

Elizabeth J. Videlock, MDMedical ResidentBeth Israel Deaconess Medical CenterBoston, MA, USA

Arnold Wald, MDProfessor of MedicineSection of Gastroenterology and HepatologyUniversity of Wisconsin School of Medicine and Public HealthMadison, WI, USA

Kymberly D.S. Watt, MDAssistant Professor of MedicineDivision of Gastroenterology and HepatologyWilliam J. von Liebig Transplant CenterMayo ClinicRochester, MN, USA

Field F. Willingham MD, MPHClinical and Research Fellow in MedicineHarvard Medical SchoolGastrointestinal UnitMassachusetts General HospitalBoston, MA, USA

Jacqueline L. Wolf, MDAssociate Professor of MedicineHarvard Medical SchoolDivision of GastroenterologyBeth Israel Deaconess Medical CenterBoston, MA, USA

Tonia M. Young-Fadok, MD, MSProfessor of SurgeryChair, Division of Colorectal SurgeryMayo ClinicScottsdale, AZ, USA

Yan Zhong, MDEndoscopy Practice am GlockengiesserwallHamburg, Germany

Timothy L. Zisman, MD, MPHAssistant Professor of MedicineDivision of GastroenterologyUniversity of Washington Medical CenterSeattle, WA, USA

Preface

Welcome to Practical Gastroenterology and Hepatology, a new comprehensive three volume resource for everyone training in gastroenterology and for those certifying (or recertifying) in the subspecialty. We have aimed to create three modern, easy to read and digest stand-alone textbooks. The entire set covers the waterfront, from clinical evaluation to advanced endoscopy to common and rare diseases every gastroenterologist must know.

Volume two specically deals with disorders of the small and large intestine, and pancreas. Each chapter highlights, where appropriate, a clinical case which demonstrates a common clinical situation, its approach, and management. Simple easy to follow clinical algorithms are demonstrated throughout the relevant chapters. Endoscopy chapters provide excellent video examples, all available electronically.

Each chapter has been written by the best of the best in the eld, and carefully peer reviewed and edited for accuracy and relevance. We have guided the writing of this textbook to help ensure experienced gastroenterolo-gists, fellows, residents, medical students, internists, primary care physicians, as well as surgeons all will nd something of interest and relevance.

Each volume and every chapter has followed a standard template structure. All chapters focus on key knowledge, and the most important clinical facts are highlighted in an introductory abstract and summary box at the end; irrelevant or unimportant information is omitted. The chapters are deliberately brief and readable; we want our readers to retain the material, and immediately be able to apply what they learn in practice. The chapters are illustrated in color, enhanced by a very pleasant layout. A Web based version has been created to complement the textbook including endoscopy images and movies.

In this volume, section one addresses the pathobiology of the intestine and pancreas, providing a scientic basis for disease. The emphasis here is, as in all volumes, on the practical and clinically relevant, as opposed to the esoteric. Section two deals with endoscopy issues including colonoscopy, ERCP and endoscopic ultrasound. Section three covers endoscopic, radiologic and physiologic testing of the small intestine and pancreas, including capsule endoscopy and balloon assisted enteroscopy. Section four approaches disorders from a problem or symptom based standpoint with a simple, clear guide to diagnosis and management strategies. Section ve covers important diseases of the small intestine including mal-absorptive diseases, Crohn’s disease, and tumors of the small intestine. Section six addresses diseases of the colon and rectum including inflammatory bowel disease, polyps, colon cancer and diverticulitis. The section on diseases of the pancreas covers both acute and chronic pancreatitis as well as pancreatic cancer and cystic neoplasms. Endoscopic palliation of malignant obstruction including related obstruction of the small intestine is reviewed. Section eight covers functional gastrointestinal disorders including irritable bowel syndrome, constipation, abdominal pain and bloating. Section nine deals with transplantation of gastrointestinal organs with specic attention to indications and postoperative management. Finally, section ten covers diseases of the peritoneum, and hernias.

We have been thrilled to work with a terric team in the creation of this work, and very much hope you will enjoy reading this volume as much as we have enjoyed developing it for you.

Nicholas J. TalleyMichael WallaceSunanda Kane

Foreword

This book is impressive for its breadth and depth, and serves an important niche for the broad readership. As leaders in the broad field of gastroenterology, the Editors, Doctors Nicholas J. Talley, Sunanda V. Kane, and Michael B. Wallace, are to be commended for undertaking this task. Covering diverse topics, the team of recruited authors is recognized for their individual and collective experience and expertise in their respective fields. The chapters are integrated through cross-referencing, annotated with key points for the readership, well illustrated, and referenced in a current fashion. In an era when one is challenged to obtain information through a variety of options, this book certainly serves that need. In that context, the book will appeal to gastroenterologists, hepa-tologists, pancreatologists, fellows, residents, students, and allied health care personnel, and be a requirement for institutional libraries.

Anil K. Rustgi, MDT. Grier Miller Professor of MedicineChief of GastroenterologyUniversity of Pennsylvania

PART 1

Pathobiology of the Intestine and Pancreas

CHAPTER 1

Clinical Anatomy, Embryology, and Congenital Anomalies

Advitya Malhotra1 and Joseph H. Sellin2

1Department of Gastroenterology and Hepatology, University of Texas Medical Branch (UTMB), Galveston, TX, USA

2Division of Gastroenterology, Baylor College of Medicine, Houston, TX, USA

Summary

As clinicians and educators we update ourselves routinely with various aspects of our practicing field. Mainly, the focus is centered on the pathogenesis, diagnosis, and management aspects of the clinical problem. Rarely, we delve in to the anatomy of the organ system responsible for the presentation. However, some embryological anomalies can present in later decades of life and present unexpected and difficult challenges in both diagnosis and management. Hence, a practical working knowledge on this subject is critical for the clinical gastroenterologist.

We have compiled a chapter that deals succinctly with the clinical anatomy, embryology, and congenital anomalies of the gastrointestinal tract. The main body of the chapter is in line with the evolving division of the gastrointestinal tract of the embryo into foregut, midgut, and the hindgut. We briefly cover the anatomy, embryogenesis, and the congenital anomalies of each derivative of the germ layer starting from the foregut, and ending with the Hirschsprung disease (HSCR), a congenital anomaly of the ganglion cells of the hindgut. Some of the more commonly seen anomalies, such as pancreas divisum (PD), are dealt in detail wherever required.

Small and Large Intestine

Anatomy and Embryogenesis

At 4 weeks of gestation, the alimentary tract is divided into three parts: foregut, midgut, and hindgut. The duodenum originates from the terminal portion of the foregut and cephalic part of the midgut. With rotation of the stomach, the duodenum becomes C-shaped and rotates to the right. The midgut gives rise to the duodenum distal to the ampulla, to the entire small bowel, and to the cecum, appendix, ascending colon, and the proximal two-thirds of the transverse colon. The distal third of the transverse colon, the descending colon and sigmoid, the rectum, and the upper part of the anal canal originate from the hindgut. The anal canal’s proximal portion is formed from the hindgut endoderm whereas the distal portion arises from the ectoderm of the cloacal membrane.

The colon has a rich blood supply, with a specific vascular arcade formed by union of branches of superior mesenteric, inferior mesenteric, and internal iliac arteries. Despite its presence, the colon vasculature has two weak points: the splenic flexure and the rectosigmoid junction which are supplied by the narrow terminal branches of superior mesenteric artery (SMA) and inferior mesenteric artery (IMA), respectively. These two watershed areas are most vulnerable to ischemia during systemic hypotension.

Aberrations in midgut development may result in a variety of anatomic anomalies (Table 1.1 ), and these are broadly classified as:

Rotation and fixationDuplicationsAtresias and stenoses: these occur most frequently and are either due to failure of recanalization or a vascular accident. Atresias have a reported incidence rate of 1 in 300 to 1 in 1500 live births, and are more common than stenoses. Atresias are more common in black infants, low birth-weight infants, and twins. Clinically, the presentation is that of a proximal intestinal obstruction with bilious vomiting on the first day of life. Treatment is surgical correction.

Table 1.1 Congenital anomalies of upper gastrointestinal tract.

The other major congenital anomalies of the intestine and abdominal cavity are related to abnormalities with development of abdominal wall, the vitelline duct, and innervation of the gastrointestinal tract.

Abdominal Wall Congenital Anomalies

The congenital anomalies of the abdominal wall are:

Gastrochisis: caused by an intact umbilical cord with evisceration of the bowel, but no covering membranes, through a defect in the abdominal wall [1] . Gastrochisis is commonly associated with intestinal atresia and cryptorchism.Omphalocele: characterized by herniation of the bowel, liver, and other organs into the intact umbilical cord; unlike gastrochisis, these tissues are covered by a membrane formed from fusion of the amnion and peritoneum.

Diagnosis

An abdominal wall defect may be diagnosed during routine prenatal ultrasonography. Both gastroschisis and omphalocele are associated with elevation of maternal serum α-fetoprotein.

Management

Recommended management for both these conditions is operative reduction of the contents back in to the abdominal cavity. The size of the omphalocele deter-mines whether a primary repair or delayed primary closure is selected as the surgical approach.

Vitelline Duct Congenital Anomalies

Persistence of the duct communication between the intestine and the yolk sac beyond the embryonic stage may result in several anomalies of the omphalomesen-teric or vitelline duct.

The most common congenital abnormality of the gastrointestinal tract is omphalomesenteric duct, or Meckel diverticulum, which results from the failure of the vitelline duct to obliterate during the fifth week of fetal development [2] .

Clinical presentation

Meckel diverticulum may remain completely asymptomatic or it may mimic such disorders as Crohn disease, appendicitis, and peptic ulcer disease. Bleeding is the most common complication of Meckel diverticulum, related to acid-induced ulceration of adjacent small intestine from the presence of ectopic gastric mucosa. Obstruction, intussusception, diverticulitis, and perforation may also occur, especially in adults, due to the active ectopic pancreatic tissue or gastric mucosa.

Diagnosis

The most useful method of detection of a Meckel diverticulum is technetium-99m pertechnetate scanning. Technetium uptake depends on the presence of hetero-topic gastric tissue. The test has 85% sensitivity and 95% specificity. The sensitivity of the scan can be increased minimally with use of cimetidine [3] . Other tests useful in diagnosis are superior mesenteric artery angiography, laparoscopy, and double balloon enteroscopy.

Management

Meckel diverticulectomy either by laparoscopy or open laparotomy approach is the procedure of choice for symptomatic diverticulum.

Less Common Vitelline Duct Abnormalities

Other, less common congenital abnormalities of vitelline duct include:

Omphalomes-enteric or vitelline cyst: central cystic dilatation in which the duct is closed at both ends but patent in its centerUmbilical-intestinal fistula: a patent duct throughout its lengthOmphalomesenteric band: complete obliteration of the duct, resulting in a fibrous cord or ligament extending from the ileum to the umbilicus.

Enteric Nervous System Anomalies

The most common enteric nervous system congenital anomaly is Hirschsprung (HSCR) disease; other associated anomalies include intestinal neuronal dysplasia (IND) and chronic intestinal pseudo-obstruction.

HSCR is characterized by the absence of ganglion cells in the submucosal (Meissner) and myenteric (Auerbach) plexuses along a variable length of the hindgut. It is classified as short-segment HSCR (80% of cases), when the aganglionic segment does not extend beyond the upper sigmoid, and long-segment HSCR when aganglionosis extends proximal to the sigmoid. Twelve percent of children with Hirschsprung disease have chromosomal abnormalities, 2 to 8% of which are trisomy 21 (Down syndrome) [4].

Clinical Presentation

In most cases, HSCR presents at birth as non-passage of meconium, abdominal distension, feeding difficulties, and/or bilious emesis. Some patients are diagnosed later in infancy or in adulthood with severe constipation, chronic abdominal distension, vomiting, and failure to thrive.

Diagnosis

The diagnosis in a symptomatic individual may be made by one or a combination of the following tests: barium enema, rectal biopsy, and anal manometry.

Management

Definitive treatment of Hirschsprung disease is surgical, and the specific method of surgery is operator dependent

Pancreas

Anatomy and Embryogenesis

The pancreas first appears during the fourth week of gestation as ventral and dorsal outpouchings from the endodermal lining of the duodenum. The normal adult pancreas results from the fusion of these dorsal and ventral pancreatic buds during the second month of fetal development. The tail, body, and part of the head of the pancreas are formed by the dorsal component; the remainder of the head and the uncinate process derive from the ventral pancreas.

Figure 1.1 Schematic illustration of embryology of normal pancreas and pancreas divisum. (Reproduced with kind permission from Springer & Business Media. Kamisawa T. Clinical significance of the minor duodenal papilla and accessory pancreatic duct. Journal of Gastroenterology 2004; 39 : 606.)

The dorsal duct arises directly from the duodenal wall, and the ventral duct arises from the common bile duct. On fusion of the ventral and dorsal components of the pancreas, the ventral duct anastomoses with the dorsal one, forming the main pancreatic duct of Wirsung (Figure 1.1 ). The proximal end of the dorsal duct becomes the accessory duct of Santorini in the adult [5] . The pancreatic acini appear in the third month of gestation as derivatives of the side ducts and termini of these primitive ducts.

Pancreas Divisum ( PD )

PD occurs when the dorsal and ventral ducts fail to fuse; the dorsal duct drains the majority of the pancreas via the minor papilla, while the short ventral duct drains the inferior portion of the head via the major papilla (Figure 1.1 ). Pancreas divisum has been observed in 5 to 10% of autopsy series and in about 2 to 7% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) [6] . Most patients with pancreas divisum are asymptomatic, and the diagnosis is made incidentally. However, some patients develop abdominal pain, recurrent acute pancreatitis, or chronic pancreatitis. The causal relationship between divisum and pancreatitis is still a matter of debate. PD is usually diagnosed by ERCP although endoscopic ultrasonography and magnetic resonance cholangiopancreatography (MRCP) may be useful for diagnosis [7] . Therapeutic intervention (either endoscopic sphincterotomy with placement of stents through the accessory papilla or surgical sphincteroplasty of the accessory papilla) may benefit some patients with PD and recurrent, acute pancreatitis associated with accessory papilla stenosis [8] .

Ectopic Pancreas

Ectopic pancreas is pancreatic tissue found outside the usual anatomic confines of the pancreas. Although it may occur throughout the gastrointestinal tract it is most commonly found in the stomach and small intestine. Usually an incidental finding, it may rarely become clinically evident when complicated by inflam-mation, bleeding, obstruction, or malignant transformation [9].

Pancreatic Agenesis

Agenesis of the pancreas is very rare and may be associated with other congenital disease states. In addition, isolated agenesis of the dorsal or, less commonly, the ventral pancreas can occur as silent anomalies [10] .

Congenital Cysts

Congenital cysts of the pancreas are rare and are distinguished from pseudocysts by the presence of an epithelial lining. True congenital cysts occur as a result of developmental anomalies related to the sequestration of primitive pancreatic ducts. They are generally asymptomatic, although abdominal distension, vomiting, jaundice, or pancreatitis can be observed requiring surgical removal.

Anomalous Pancreaticobiliary Ductal Union ( APBDU )

APBDU is a congenital malformation of the confluence of the pancreatic and bile ducts. A classification has been developed for APBDU: if the pancreatic duct appears to join the common bile duct, this is classified as a P–B type. If the common bile duct joins the main pancreatic duct, this is a B–P type. A long common channel is denoted Y type. The frequency of APBDU varies from 1.5 to 3 2%. APBDU is associated with pancreatitis (with long >21 mm and wide > 5 mm common channel), choledochal cysts, and neoplastic abnormalities like cholangiocarcinoma and pancreatic cancer in adults [11] .

Take-home points

Small and large intestine:

The colon vasculature has two weak points; the splenic flexure and the rectosigmoid junction which are supplied by the narrow terminal branches of SMA and IMA, respectively. These two watershed areas are most vulnerable to ischemia during systemic hypotension.The two common congenital anomalies of the abdominal wall presenting at birth are gastrochisis and omphalocele.The most common congenital abnormality of the gastrointestinal tract is omphalomesenteric duct, or Meckel diverticulum, which results from the failure of the vitelline duct to obliterate during fetal development.The most common enteric nervous system congenital anomaly is Hirschsprung (HSCR) disease, which is characterized by the absence of ganglion cells in the submucosal (Meissner) and myenteric (Auerbach) plexuses along a variable length of the hindgut.

Pancreas:

Pancreas divisum occurs when the dorsal and ventral ducts fail to fuse; the dorsal duct drains the majority of the pancreas via the minor papilla, while the short ventral duct drains the inferior portion of the head via the major papilla.

References

1 Weber T, Au-Fliegner M, Downard C, Fishman S. Abdominal wall defects . Curr Opin Pediatr 2002; 14: 491–7.

2 Turgeon D , Barnett J . Meckel’s diverticulum . Am J Gastro-enterol 1990; 85: 777–81.

3 Petrokubi R, Baum S, Rohrer G. Cimetidine administration resulting in improved pertechnetate imaging of Meckel’s diverticulum. Clin Nucl Med 1978; 3: 385–8.

4 Skinner M. Hirschsprung’s disease. Curr Probl Surg 1996; 33: 389–460.

5 Kleitsch W . Anatomy of the pancreas; a study with special reference to the duct system . AMA Arch Surg 1955; 71: 795–802.

6 Delhaye M , Engelholm L , Cremer M . Pancrease divisum: congenital anatomic variant or anomaly? Contribution of endoscopic retrograde dorsal pancreatography . Gastroenter-ology 1985; 89: 951–8.

7 Bret P, Reinhold C, Taourel P, et al . Pancreas divisum: evaluation with MR cholangiopancreatography . Radiology 1996; 199: 99–103.

8 Lans J, Geenen J, Johanson J, Hogan W. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a prospective, randomized, controlled clinical trial . Gastroin-test Endosc 1992; 38: 430–4.

9 Eisenberger C, Gocht A, Knoefel W, et al. Heterotopic pancreas—clinical presentation and pathology with review of the literature . Hepatogastroenterology 2004; 51: 854–8.

10 Fukuoka K, Ajiki T, Yamamoto M, et al. Complete agenesis of the dorsal pancreas . J Hepatobiliary Pancreat Surg 1999 ; 6: 94–7.

11 Wang H, Wu M, Lin C, et al. Pancreaticobiliary diseases associated with anomalous pancreaticobiliary ductal union . Gastrointest Endosc 1998; 48: 184–9.

CHAPTER 2

Physiology of Weight Regulation

Louis Chaptini, Christopher Deitch, and Steven Peikin

Division of Gastroenterology and Liver Diseases, Cooper University Hospital, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden, NJ, USA

Summary

The interest in the physiology of weight regulation has increased in recent years due to the major deleterious effects of the obesity epidemic on public health. A complex neuroendocrine network involving peripheral organs and the central nervous system is responsible for maintaining a balance between energy intake and expenditure. Major change in weight can result from an imbalance in this network. Gut and adipose tissue are the main peripheral organs involved in weight regulation. Hormones are secreted from these peripheral organs in response to nutrient intake and weight fluctuation. They are subsequently integrated by the central nervous system. Unraveling these peripheral and central signals and their complex interaction at multiple levels has an essential role in understanding the physiology of weight regulation.

Introduction

The physiology of weight regulation has gained tremendous interest in recent decades because of the major deleterious effects of overweight and obesity on public health. More than 300 000 deaths per year are attributed to obesity [1] and poor diet and inactivity may soon overtake tobacco as a leading cause of death in the USA [2] . Complex brain–gut interaction constitutes the basis of weight regulation and involves intricate mechanisms, some of which are not fully elucidated thus far and are focus of extensive ongoing research. This chapter reviews the current understanding of the mechanisms of weight regulation with emphasis on the role of the gastrointestinal system.

Concept of Energy Homeostasis

Fat is the primary form of energy storage in the human body. According to the first law of thermodynamics, the amount of stored energy is equal to the difference between energy intake and energy expenditure. Under normal conditions, homeostatic mechanisms maintain the difference between energy intake and energy expenditure close to zero. A very small imbalance in those mechanisms over a long period of time can result in large cumulative effects, leading to a major change in weight. In order to keep a perfect balance between energy intake and expenditure, homeostatic mechanisms rely on neural signals that emanate from adipose tissue, endocrine, neurological, and gastrointestinal systems and are integrated by the central nervous system (CNS) [3,4] . The CNS subsequently sends signals to multiple organs in the periphery in order to control energy intake and expenditure and maintain energy homeostasis over long periods of time (Figure 2.1).

Role of the Central Nervous System

During recent decades, extensive research has focused on the role of the CNS in the regulation of food intake and the pathogenesis of obesity. Eating in humans is thought to follow a dual model: “reflexive” eating that represents automatic impulses to overeat in anticipation for a coming food shortage and “reflective eating” that incorporates a cognitive dimension involving social expectations of body shape and long-term health goals [5]. Reflexive eating is represented by the brainstem and the arcuate nucleus. Two populations of neurons are responsible for the regulation of food intake in the arcuate nucleus, one expressing neuropeptide Y (NPY) and agouti-related peptide (AgRP), which when activated leads to an orexigenic response and reduced energy expenditure, and the other containing pro-opiomelano-cortin (POMC) and cocaine and amphetamine-regulated transcript (CART), where increased activity results in an increase in energy expenditure and a decrease in food intake [6] . NPY is one of the hormones that constitute the pancreatic polypeptide family, which includes two other hormones, pancreatic polypeptide (PP) and peptide YY (PYY). NPY is present in large quantities in the hypothalamus and is one of the most potent orexigenic factors [7] . Among NPY receptors, the Y5 receptors have been implicated as important mediators of the feeding effect and the Y5 receptors antagonists have been involved in recent weight loss studies [8] . The brain cortex seems to play a role in the regulation of food intake and represents the “reflective eating” [5] . The right prefrontal cortex (PFC) has been specifically involved in the cognitive inhibition of food intake.

Figure 2.1 Pathways of regulation of food intake. Representation of the potential action of gut peptides on the hypothalamus. Primary neurons in the arcuate nucleus contain multiple peptide neuromodulators. Appetite-inhibiting neurons (red) contain pro-opiomelanocortin (POMC) peptides such as α melanocyte -stimulating hormone (αMSH), which acts on melanocortin receptors (MC3 and MC4) and cocaine- and amphetamine-stimulated transcript peptide (CART), whose receptor is unknown. Appetite-stimulating neurons in the arcuate nucleus (blue) contain neuropeptide Y (NPY), which acts on Y receptors (Y1 and Y5), and agouti-related peptide (AgRP), which is an antagonist of MC3/4 receptor activity. Integration of peripheral signals within the brain nvolves interplay between the hypothalamus and hindbrain structures including the nucleus of the tractus solitarius (NTS), which receives vagal afferent inputs. Inputs from the cortex, amygdala, and brainstem nuclei are integrated as well, with resultant effects on meal size and frequency, gut handling of ngested food, and energy expenditure. →, direct stimulatory; ┤, direct inhibitory; PYY, peptide tyrosine tyrosine; PP, pancreatic polypeptide; GLP-1, glucagon-like peptide-1; OXM: oxyntomodulin; CCK: cholecystokinin. (Adapted from Badman and Flier [4] )

Role of Adipose Tissue

Insulin and leptin are adiposity signals that play an important role in the physiology of weight regulation.

Insulin receptors are widely present in the CNS. Insulin levels have been shown to correlate with body adiposity. Increase in food intake and adiposity can result from hypothalamic defects in insulin signaling [9] .

C irculating levels of leptin, an adipocyte-derived hormone, reflect the adipose tissue mass as well as recent nutritional status. The action of leptin in the CNS results in decrease in food intake and increase in energy expenditure through the inhibition of NPY/AgRP neurons and activation of POMC neurons [10] . Most obese humans have elevated serum leptin levels, which suggests leptin resistance may be important in human obesity. Manipulating leptin resistance may provide an interesting target for obesity treatment.

Adiponectin and resistin are two other peptides produced by adipocytes. Low levels of the former are associated with insulin resistance, dyslipidemia, and atherosclerosis, whereas the latter has proinflammatory effects and has also been implicated in insulin resistance [11,12] .

Role of the Gastrointestinal Tract

The gastrointestinal tract elicits neural and endocrine signals that play a major role in food intake regulation. The interaction of gastrointestinal hormones with the brain constitutes the gut–brain axis which has been extensively studied in the past decade.

Role of the Stomach in Food Intake Regulation

Gastric distension

Gastric distension has been shown in multiple studies to serve as a signal for satiety. Instillation of a volume load in the stomach leads to distension of gastric wall, which in turn induces satiety regardless of the nature of the load: in rats, studies have shown that equivalent volumes of saline or different nutrient solutions produce equivalent reduction in food intake [13,14] .

Ghrelin

Ghrelin is a peptide predominantly produced by the stomach and its secretion is increased by fasting and in response to weight loss and decreased by food intake. Ghrelin is the only known circulating appetite stimulant. It stimulates appetite by acting on arcuate nucleus NPY/ AgRP neurons and may also inhibit POMC neurons [15] . There is also evidence that the vagus nerve is required to mediate the orexigenic effect of ghrelin. Ghrelin plays a role in meal initiation which is demonstrated by a premeal surge in plasma ghrelin levels in humans and animals. In addition to its role in short-term regulation of food intake (meal initiator), ghrelin appears to participate in long-term energy homeostasis, which is suggested by its fluctuation in response to body weight variations [16].

Role of the Pancreas and Small Intestine in Food Intake Regulation

Cholecystokinin ( CCK )

CCK is the prototypical satiety hormone, produced by cells in the duodenum and jejunum. It is produced in response to the presence of nutrients within the gut lumen, specifically fat and protein. The satiating effect of CCK is mediated through paracrine interaction with sensory fibers of the vagus nerve. It inhibits food intake by reducing meal size and duration [17] . CCK has a short half-life which makes it a very short-term modulator of appetite.

Peptide Tyrosine Tyrosine (PYY) and Pancreatic Polypeptide (PP)

PYY and PP are members of the pancreatic polypeptide family which also includes NPY discussed earlier. PYY is secreted by enteroendocrine L-cells, mainly in the distal portion of the gastrointestinal tract. It is released following meals (acting as meal terminator) and suppressed by fasting, exactly opposite to the pattern of secretion seen with ghrelin [17] . PP is secreted in response to a meal, in proportion to the caloric load, and has been shown to reduce appetite and food intake [18] . It is produced mainly in the endocrine pancreas, but also in the exocrine pancreas, colon, and rectum.

Glucagon-like peptide-1 (GLP-1) and Oxyntomodulin

GLP-1 and oxyntomodulin derive from the post -translational processing of proglucagon, which is expressed in the gut, pancreas, and brain. GLP-1 is secreted by enteroendocrine L-cells in the distal small bowel in response to direct nutrient stimulation in the distal small intestine as well as indirect neurohumoral stimulation in proximal regions of the small intestine. The actions of GLP-1 include inhibition of gastric emptying, stimulation of insulin release, inhibition of glucagon release and inhibition of appetite [19] . Oxyntomodulin is secreted in the distal small intestine as well. It binds but has lower affinity to the GLP-1 receptor. It has been shown to decrease energy intake and, moreover, increase energy expenditure [20] .

Conclusion

The physiology of weight regulation involves intricate interaction between the brain and the gut. Tremendous progress in the understanding of the different components of the gut brain axis has been achieved and extensive research is underway to create agents targeting these different components to accomplish significant and lasting weight reduction.

Take-home points

Understanding the physiology of weight regulation is fundamental in the fight against the obesity epidemic.Maintaining a stable weight involves complex homeostatic mechanisms responsible for a perfect balance between energy expenditure and energy intake.Signals originating from peripheral organs, such as adipose tissue and gastrointestinal system, and integrated by the central nervous system constitute the homeostatic mechanisms responsible for weight regulation.Gut hormones are produced in response to nutrient intake and weight fluctuation.Targeting complex peripheral and central signals involved in weight regulation is the mainstay in the development of weight reduction therapeutic agents.

References

1 Fontaine KR , Redden DT , Wang C , et al . Years of life lost due to obesity . JAMA 2003; 289: 187–93.

2 Allison DB , Fontaine KR , Manson JE , et al . Annual deaths attributable to obesity in the United States . JAMA 1999; 282: 1530–8.

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CHAPTER 3

Small Intestinal Hormones and Neurotransmitters

Nithin Karanth1 and James C. Reynolds 2

1Department of Gastroenterology, Drexel University College of Medicine, Philadelphia, PA, USA

2