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Volume 2, Supplement 2, 2002

Volume 2, Supplement 2, 2002

Table of Contents

Mechanisms of Epithelial Injury and Inflammation in Gastrointestinal Diseases
Using Barrett’s esophagus and Crohn’s disease as models of gastrointestinal disorders, a number of key mechanisms of cell injury and death and chronic inflammation are reviewed. Among them are the roles of impaired osmoregulation, elevated cytosolic calcium, activation of the mitochondrial permeability transition and levels of cytosolic adenosine triphosphate as determinates of cell death as well as the role of inflammatory cells, cytokines, NOD2 gene products, and reactive oxygen species in chronic inflammation. Further, the basis for the link between inflammation and cancer risk in Barrett’s esophagus and Crohn’s disease is described. [Rev Gastroenterol Disord. 2002;2(suppl 2):S2–S8]
Initial Therapy for Mild to Moderate Crohn's Disease: Mesalamine or Budesonide?
The initial choice of therapy for mild to moderately active Crohn’s disease is controversial. Both the National Cooperative Crohn’s Disease Study (NCCDS) and the European Cooperative Crohn’s Disease Study (ECCDS) demonstrated that sulfasalazine is effective for the induction of remission. Subsequent studies of new mesalamine formulations showed inconsistent results; two trials, however, demonstrated a statistically significant improvement with Pentasa and Asacol treatment, and meta-analyses suggest a modest benefit of mesalamine maintenance therapy. The NCCDS and ECCDS trials found that corticosteroid therapy is much more effective than sulfasalazine for induction of remission, but corticosteroids did not show maintenance benefits. Corticosteroid use is frequently associated with adverse effects, and the majority of patients treated with prednisone become either steroid-refractory or steroid-dependent; many of these patients ultimately need treatment with immunosuppressives and/or surgery. Budesonide, a topical corticosteroid with high first-pass hepatic metabolism, is slightly less effective in inducing remission than conventional corticosteroids but is significantly less likely to cause side effects. Budesonide 9 mg/day was shown to be more effective than mesalamine (Pentasa 4 g/day) for induction therapy, but budesonide has been ineffective as a maintenance therapy. Mesalamine may be useful for patients with more extensive disease, those intolerant of sulfasalazine, or those with contraindications or intolerance to budesonide. Alternatively, sulfasalazine is effective in the presence of colonic disease. Clinicians must decide on the basis of the existing evidence whether budesonide or mesalamine is the preferred initial therapy for active Crohn's disease. [Rev Gastroenterol Disord. 2002;2(suppl 2):S9–S15]
Reduction of Colorectal Cancer Risk in Patients with Crohn's Disease
Patients with inflammatory bowel disease (IBD)—either Crohn’s disease (CD) or ulcerative colitis (UC)—are at increased risk for developing cancers of the gastrointestinal tract, particularly colorectal cancer (CRC). Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk; nonetheless, within particular subsets of IBD patients, the cumulative risk of developing dysplasia and CRC may be substantial. Efforts to reduce this risk have included both prophylactic surgery and endoscopic screening programs. Despite the impact this disease has on quality of life and life expectancy, an optimal strategy for reducing the risk has yet to be defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods available to help reduce this risk. [Rev Gastroenterol Disord. 2002;2(suppl 2):S16–S24]
Screening for Barrett's Esophagus
Screening and surveillance for Barrett’s esophagus have been proposed as strategies for preventing deaths from esophageal adenocarcinoma. A meaningful discussion on the cost efficacy of screening and surveillance for Barrett’s esophagus requires a reasonable estimate of the risk of esophageal cancer in this condition. The primary goal of endoscopic screening for individuals with gastroesophageal reflux disease is to identify patients with Barrett’s esophagus who will benefit from an intervention to prevent cancer. There is also indirect evidence to suggest that surveillance for Barrett’s esophagus may be beneficial. However, there is much debate over the efficacy of these diagnostic procedures. In the absence of definitive data, investigators have used computer models to study the cost effectiveness of screening and surveillance for Barrett’s esophagus. It is important for physicians to recognize that such models do not provide a single, definitive answer. [Rev Gastroenterol Disord. 2002;2(suppl 2):S25–S29]
Does Chemoprevention of Barrett's Esophagus Using Acid Suppression and/or COX-2 Inhibition Prevent Neoplastic Progression?
Barrett’s esophagus—intestinal metaplasia within the tubular esophagus—is a premalignant histologic lesion and a marker of cancer risk. Strategies to prevent Barrett’s-related esophageal cancer have focused on reversal of Barrett’s using pharmacological or surgical antireflux therapies and endoscopically-induced injury. Currently, however, there is little compelling evidence to support the reversal of Barrett’s through pharmacological or surgical therapy, and endoscopic reversal of Barrett’s has not yet been validated. Chemoprevention using intensive acid suppression and/or inhibition of cycoloxygenase-2 (COX-2) with nonsteroidal anti-inflammatory drugs remains a biologically plausible strategy that is supported by a rapidly growing body of scientific evidence. Data suggest that a combination of acid suppression with COX-2 inhibition might be the most effective chemopreventive strategy. Whether this approach is effective awaits the results of well-designed outcomes studies. [Rev Gastroenterol Disord. 2002;2(suppl 2):S30–S37]