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Brief Title: Effect of Antireflux Therapy on the Expression of Genes in Patients With GERD
Official Title: Effect of Antireflux Therapy on the Expression of Genes Known to be Important in Inflammation, Metaplasia and Neoplasia in Patients With GERD
Study ID: NCT00624546
Brief Summary: Although the symptomatic and epithelial (histologic and endoscopic) response to antireflux therapy are well known and extensively studied, little is known of the genetic events occurring in response to proton pump inhibitor therapy. Preliminary data from our laboratory has shown, for example, that COX-2 expression is not only elevated in patients with gastroesophageal reflux disease but also can be correlated with pathologic esophageal acid exposure on 24 hour pH monitoring. Similar studies have suggested that antireflux surgery may normalize COX-2 gene expression. In contrast studies following ablation of dysplastic Barrett's epithelium have shown persistence of genetic changes associated with altered cellular function, despite the return of the histologic appearance to normal. Several key mediators of inflammation, metaplasia (Barrett's) and neoplasia have now been well characterized and shown to be important factors in the pathogenesis of esophageal injury. It is likely that successful antireflux therapy returns altered expression of these mediators toward normal although this hypothesis remains largely unexplored. The aim of this study is to investigate gene expression of key mediators of the spectrum of esophageal mucosal injury and the response to antireflux therapy. Hypothesis: Antireflux therapy (proton pump inhibitor and surgical fundoplication) normalizes the expression of genes known to be involved in the pathogenesis of inflammation (esophagitis), metaplasia (Barrett esophagus) and neoplasia (adenocarcinoma).
Detailed Description: Aims: To determine the effects of antireflux therapy (pump inhibitor and surgical fundoplication) on gene expression of: 1. inflammation: IL-8, IFN-g, TNF-a. 2. intestinal metaplasia: CDX-1/2, MUC2 and Sonic hedgehog. 3. Neoplasia: Cox-2, VEGF, and EGFR.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
Strong Memorial Hospital, Rochester, New York, United States
Name: Jeffrey H Peters
Affiliation: University of Rochester
Role: PRINCIPAL_INVESTIGATOR