Research Project
9479687
Project Summary In patients with gastroesophageal reflux disease (GERD), acid and bile in the stomach reflux into the esophagus and damage its normal, squamous epithelial lining. Many patients with GERD develop a condition called Barrett?s esophagus in which an abnormal, intestinal-type epithelium called Barrett?s metaplasia replaces the esophageal squamous epithelium that has been damaged by GERD. Barrett?s esophagus, which is estimated to affect 5.6% of adult Americans, is a major risk factor for a deadly type of cancer called esophageal adenocarcinoma. A recently-developed endoscopic procedure called radiofrequency ablation (RFA), which uses microwave energy to destroy the Barrett?s metaplasia, can decrease the cancer risk for patients with Barrett?s esophagus. After RFA, patients are treated with medications that control GERD, and their ablated Barrett?s esophagus heals with re-formation of the normal squamous epithelial lining. Presently, very little is known of the process by which the esophageal wound inflicted by RFA heals and, for reasons that are not clear, the pre-cancerous Barrett?s metaplasia often returns after it has been eradicated by RFA. An understanding of the mechanisms underlying RFA wound healing is needed to develop strategies to prevent these frequent recurrences of Barrett?s metaplasia. We think that RFA wounds heal through a unique mechanism in which squamous progenitor cells in the ducts of glands that are located deep in the wall of the esophagus, beyond the reach of the injury inflicted by RFA, provide the squamous cells that re-line the RFA wound when GERD is controlled. The aim of our project is to characterize the endoscopic, histologic, and molecular features of esophageal epithelial wound healing following RFA of Barrett?s metaplasia. We propose to study 10 patients with Barrett?s esophagus who we will treat with medications called proton pump inhibitors, which are very effective at controlling GERD. We will perform endoscopy with RFA of Barrett?s metaplasia, and patients will have endoscopy repeated to assess healing of the esophageal wound at 7, 14 and 28 days after RFA. At each endoscopy, patients will have photographs taken of the esophagus to document the healing pattern, and esophageal biopsies will be taken to determine the histologic type, molecular characteristics, and gene expression profiles of the cells contributing to the healing of the RFA wound. In additional to conventional, high-definition, white light endoscopy, patients will also have confocal laser endomicroscopy, an endoscopic procedure that provides 1000-fold magnification of the esophageal epithelium. Ultimately, we plan to use the information gleaned from this study on how RFA wounds heal to develop strategies to prevent recurrences of Barrett?s metaplasia after RFA.
