At least two thirds of cirrhotic patients develop esophageal varices during their lifetime. Severe upper gastrointestinal (UGI) bleeding as a complication of portal hypertension develops in about 30%-40% of cirrhotics. Despite significant improvements in the early diagnosis and treatment of esophagogastric variceal hemorrhage, the mortality rate of first variceal hemorrhage remains high (20%-35%). Primary prophylaxis, the focus of this article, is treatment of patients who never had previous variceal bleeding to prevent the first variceal hemorrhage. The potential of preventing first variceal hemorrhage offers the promise of reducing mortality, morbidity, and associated health care costs. This article (1) reviews endoscopic grading of size and stigmata for esophageal and gastric varices, (2) describes data on prevalence and incidence of esophageal and gastric varices from prospective studies, (3) discusses independent risk factors from multivariate analyses of prospective studies for development of first esophageal or gastric variceal hemorrhage and possible stratification of patients based on these risk factors, (4) comments on the potential cost effectiveness of screening all newly diagnosed cirrhotic patients and treating high-risk patients with medical or endoscopic therapies, and (5) recommends further studies of endoscopic screening, stratification, and outcomes in prospective studies of endoscopic therapy. The author's recommendations are to perform endoscopic screening for the following subgroups of cirrhotics: all newly diagnosed cirrhotic patients and all other cirrhotics who are medically stable, willing to be treated prophylactically, and would benefit from medical or endoscopic therapies. Exclude patients who are unlikely to benefit from prophylactic therapies designed to prevent the first variceal hemorrhage, those with short life expectancy, and those with previous UGI hemorrhage (they should have already undergone endoscopy). For low or very low risk cirrhotic patients-those found to have no varices or small varices without stigmata-repeat endoscopy is recommended because screening for progression may be warranted in 2 or more years.

Hepatocellular carcinoma is the most frequent primary malignancy of the liver and appears to be rising in incidence in the United States and other developed western countries. Imaging studies play a key role in diagnosis of hepatocellular carcinoma, and more and more commonly, patients are being diagnosed at an asymptomatic stage. The use of triphasic computed tomography scanning and improved magnetic resonance imaging equipment and protocols has led to greater sensitivity and specificity for these techniques in diagnosis of hepatocellular carcinoma. Accurate staging of hepatocellular carcinoma is important in determining prognosis and in helping decide the best treatment for each patient. No one staging system appears optimal, but important factors to be considered are the size of the tumor, severity of underlying liver disease, and the functional status of the patient. Liver transplantation has grown in importance as a treatment for hepatocellular carcinoma but may be limited by availability of donor organs and long waiting times. This situation may be improved by greater use of living donor liver transplantation. Hepatic resection remains an important treatment modality for hepatocellular carcinoma, particularly in the absence of cirrhosis. Tumor ablation by alcohol injection or radiofrequency ablation is associated with favorable outcomes and may be considered a potentially curative treatment. Early diagnosis of hepatocellular carcinoma remains a key goal in improving the poor prognosis of this form of liver cancer. Identifying hepatocellular carcinoma at an early stage is often associated with having better treatment options for patients with small, asymptomatic tumors.

Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. Many biologic therapies are being evaluated for the treatment of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571) and to the leukocyte adhesion molecule alpha4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for inflammatory bowel disease include: p55 tumor necrosis factor binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide (blocks NF-kappaB); granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; anti-sense intercellular adhesion molecule-1; and the tumor necrosis factor receptor fusion protein etanercept. Based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of inflammatory bowel disease.

Barrett's esophagus is an acquired condition resulting from severe esophageal mucosal injury. It still remains unclear why some patients with gastroesophageal reflux disease develop Barrett's esophagus whereas others do not. The diagnosis of Barrett's esophagus is established if the squamocolumnar junction is displaced proximal to the gastroesophageal junction and if intestinal metaplasia is detected by biopsy. Despite this seemingly simple definition, diagnostic inconsistencies remain a problem, especially in distinguishing short segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Barrett's esophagus would be of little importance were it not for its well-recognized association with adenocarcinoma of the esophagus. The incidence of esophageal adenocarcinoma continues to increase and the 5-year survival rate for this cancer remains dismal. However, cancer risk for a given patient with Barrett's esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's esophagus or with endoscopic surveillance of patients with known Barrett's esophagus. Current screening and surveillance strategies are inherently expensive and inefficient. New techniques to improve the efficiency of cancer surveillance are evolving rapidly and hold the promise to change clinical practice in the future. Treatment options include aggressive acid suppression, antireflux surgery, chemoprevention, and ablation therapy, but there is still no clear consensus on the optimal treatment for these patients.

Molecular biology-based assays are invaluable tools for the management of chronic viral hepatitis. They can be used to test blood donations, diagnose active infection, help to establish the prognosis, guide treatment decisions, and assess the virological response to therapy. This article reviews current molecular biology-based techniques and assays, and their practical use in the management of hepatitis B and C virus infection.

The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000.

Comorbid or extraintestinal symptoms occur frequently with irritable bowel syndrome and account for up to three fourths of excess health care visits. This challenges the assumption that irritable bowel is a distinct disorder. The aims of this study were to (1) assess comorbidity in 3 areas: gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders; and (2) evaluate explanatory hypotheses.