Diseases of the Gastrointestinal Tract and Associated Infections

Contents

Preface xiii

Guy D. Eslick

Dedication xv

Infectious Causes of Esophageal Cancer 845

Guy D. Eslick

There are very few data linking infectious agents and esophageal cancer.There are conflicting data for some viruses, notably human papillomavirus,but very few data for bacteria, parasites, fungi, or yeast. Esophageal canceris increasing in Western countries and the reasons for this remain unknown.

Gastric Cancer: An Infectious Disease 853

M. Blanca Piazuelo, Meira Epplein, and Pelayo Correa

The role of infectious agents and chronic inflammation in carcinogenesis isbeing increasingly recognized. It has been estimated that about 18% ofcancers are directly linked to infections, particularly gastric adenocarci-noma (Helicobacter pylori), cervical carcinoma (human papilloma viruses),and hepatocarcinoma (hepatitis B and C viruses). Multiple clinical trials ofCOX-2 inhibitors and other antiinflammatory agents have shown a benefi-cial effect on the development of diverse tumors, such as those of thecolon, stomach, prostate, and breast. However, their mechanism of actionis not completely understood and may differ among the infectious agentsand tumor types. Because gastric adenocarcinomas account for morethan 90% of all gastric malignancies, this review focuses onadenocarcinomas.

Cholangiocarcinoma: New Insights into Disease Pathogenesis and Biology 871

Chiara Braconi and Tushar Patel

Cholangiocarcinomas are rare malignant tumors whose incidence isincreasing worldwide. Risk factors for this malignancy include both infec-tious and non-infectious diseases characterized by chronic inflammationof the bile duct epithelia. Diagnosis of these cancers remains difficult be-cause of the lack of sensitive diagnostic tests. The prognosis is poor prob-ably because of the lack of effective treatments for unresectable cancer.

Infectious Diseases and the Gallbladder 885

Kabir Julka and Cynthia W. Ko

Infections of the gastrointestinal tract can often involve the gallbladder.Infection probably plays a role in the formation of gallstones but is more

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commonly thought to contribute to acute illness in patients. Acute calcu-lous cholecystitis caused by an impacted gallstone is often complicatedby secondary bacterial infection and is a major cause of morbidity andeven mortality in patients. A wide variety of organisms can be associatedwith acute acalculous cholecystitis, a less common but potentially moresevere form of acute cholecystitis. This review focuses on infections andtheir role in the above-mentioned processes involving the gallbladder.

Epidemiology andManagement of Hepatocellular Carcinoma 899

Ju Dong Yang and Lewis R. Roberts

Hepatocellular carcinoma (HCC) is a major world health problem becauseof the high incidence and case fatality rate. In most patients, the diagnosisof HCC is made at an advanced stage, which limits the application of cu-rative treatments. Most HCCs develop in patients with underlying chronicliver disease. Chronic viral hepatitis B and C are the major causes of livercirrhosis and HCC. Recent improvements in treatment of viral hepatitis andin methods for surveillance and therapy for HCC have contributed to bettersurvival of patients with HCC. This article reviews the epidemiology, cause,prevention, clinical manifestations, surveillance, diagnosis, and treatmentapproach for HCC.

Acute Pancreatitis with an Emphasis on Infection 921

Lutz Schneider, Markus W. Buchler, and Jens Werner

Acute pancreatitis is an inflammatory disease that is mild and self-limitingin about 80% of cases. However, severe necrotizing disease still hasa mortality of up to 30%. Differentiated multimodal treatment conceptsare needed for these patients, including a multidisciplinary team (intensiv-ists, gastroenterologists, interventional radiologists, and surgeons). Theprimary therapy is supportive. Patients with infected pancreatic necrosiswho are septic undergo interventional or surgical treatment, ideally not be-fore the fourth week after onset of symptoms. This article reviews the path-ophysiologic mechanisms of acute pancreatitis and describes clinicalpathways for diagnosis and management based on the current literatureand guidelines.

Small Intestinal Bacterial Overgrowth 943

Eamonn M.M. Quigley and Ahmed Abu-Shanab

Despite the current increase in interest in the role of the microbiota inhealth and disease and the recognition, for over 50 years, that an excessof colonic-type flora in the small intestine could lead to a malabsorptionsyndrome, small intestinal overgrowth remains poorly defined. This lackof clarity owes much to the difficulties that arise in attempting to arriveat consensus with regard to the diagnosis of this condition: there is cur-rently no gold standard and the commonly available methodologies (theculture of jejunal aspirates and a variety of breath tests) suffer from consid-erable variations in their performance and interpretation, leading to varia-tions in the prevalence of overgrowth in a variety of clinical contexts.

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Treatment is similarly supported by a scant evidence base and the mostcommonly used antibiotic regimens owe more to custom than clinicaltrials.

Pathogenic Factors Involved in the Development of Irritable Bowel Syndrome:Focus on a Microbial Role 961

Carolina M. Bolino and Premysl Bercik

Irritable bowel syndrome (IBS) is a symptom complex characterized byrecurrent abdominal pain or discomfort, and accompanied by abnormalbowel habits, in the absence of any discernible organic abnormality. Itsorigin remains unclear, partly because multiple pathophysiologic mecha-nisms are likely to be involved. A significant proportion of patients developIBS symptoms after an episode of gastrointestinal infection. In addition togastrointestinal pathogens, recent evidence suggests that patients withIBS have abnormal composition and higher temporal instability of theirintestinal microbiota. Because the intestinal microbiota is an importantdeterminant of normal gut function and immunity, this instability may con-stitute an additional mechanism that leads to symptom generation and IBS.More importantly, a role for altered microbiota composition in IBS raisesthe possibility of therapeutic interventions through selective antibiotic orprobiotic administration. The new concept of functional bowel diseasesincorporates the bidirectional communication between the gut and thecentral nervous system (gut–brain axis), which may explain the multiplefacets of IBS by linking emotional and cognitive centers of the brain withperipheral functioning of the gastrointestinal tract and vice versa.

Influences of Intestinal Bacteria in Human Inflammatory Bowel Disease 977

Rachel Vanderploeg, Remo Panaccione, Subrata Ghosh, and Kevin Rioux

Microbes that reside in the human intestinal tract and interact with immuneand epithelial cells are strongly implicated as causative or predisposingagents of inflammatory bowel disease (IBD). Recent studies using metage-nomic approaches have revealed differences in the fecal and mucosa-associated microbiota of patients with IBD, but it remains unclear whetherthis is a cause or consequence of chronic intestinal inflammation. A fewmicrobes have been singled out as candidate pathogens in IBD and re-main the subject of ongoing study. Complex imbalances in gut bacterialcommunity structure and/or deficiencies in their functional capabilitiesmay be a greater issue in IBD development. A more complete understand-ing of host-microbiota interactions in IBD is hampered by several remain-ing but surmountable methodological and technical challenges.

Infectious Causes of Appendicitis 995

Laura W. Lamps

The pathologic spectrum of the inflamed appendix encompasses a widerange of infectious entities, some with specific histologic findings, andothers with nonspecific findings that may require an extensive diagnostic

Contentsx

evaluation. The appendix is exclusively involved in some of these disor-ders, and in others may be involved through extension from other areasof the gastrointestinal tract. This review discusses the pathologic featuresof bacterial, viral, fungal, and parasitic infections affecting the appendix,including adenovirus; cytomegalovirus; Yersinia, Actinomyces, Mycobac-terium, or Histoplasma species; Enterobius vermicularis; schistosomiasis;and Strongyloides stercoralis. Pertinent ancillary diagnostic techniquesand the clinical context and significance of the various infections arealso discussed.

Infectious Causes of Colorectal Cancer 1019

Nazia Hasan, Ari Pollack, and Ilseung Cho

Colorectal cancer is a major cause of cancer-related morbidity and mortal-ity in the United States and many other regions of the world. Our under-standing of the pathogenesis of colorectal cancer, from the precursoradenomatous polyp to adenocarcinoma, has evolved rapidly. Colorectalcarcinogenesis is a sequential process characterized by the accumulationof multiple genetic and molecular alterations in colonic epithelial cells.However, the development of colorectal cancer involves more then justa genetic predisposition. External or environmental factors presumablyplay a significant role, and inflammatory bowel diseases, obesity, alcoholconsumption, and a diet high in fat and low in fiber have all been implicatedas risk factors for the development of either colonic adenomas or carc-inomas. We are becoming increasingly aware of microbes as causes ofmalignancies. This article reviews the various microbes that have beenassociated with the development of colorectal carcinomas.

Future Perspectives on Infections Associated with Gastrointestinal Tract Diseases 1041

Guy D. Eslick

There are a vast number of infectious agents that are associated with gas-trointestinal (GI) tract diseases. The epidemiology of GI diseases is chang-ing, with a greater number of conditions increasing in incidence.Challenges exist with establishing cause-and-effect relationships becauseof the ubiquitous nature of these organisms and the milieu in which theyexist. Advances in technology should provide novel methods for identify-ing and diagnosing these organisms and the relationship they have witha specific digestive disease.

Index 1059