Gastroesophageal reflux disease - complications and prognostic aspects

Abstract: This thesis investigates several aspects on gastroesophageal reflux disease (GERD) and associated complications as Barrett’s esophagus and esophageal adenocarcinoma. I. To clarify the natural course of GERD, a pH-metry verified cohort was re-evaluated after 20 years. The course of GERD may well be progressive. A statement based on the evidence that reflux induced complications as esophagitis and Barrett’s esophagus increased significantly. II. A myotomised achalasia with an abolished antireflux barrier (upon an aperistaltic esophagus), creates an unrestrained gastroesophageal reflux and can therefore be regarded as an end-stage reflux disease. This clinical trial was to compare the long-term outcome for patients with an end-stage reflux disease (achalasia) who underwent Heller’s esophagomyotomy with or without an additional Nissen fundoplication. Heller’s esophagomyotomy induces advanced reflux. The complications induced by reflux and the need for acid suppressants can successfully be eliminated by an additional antireflux repair. III. Defective mismatch repair (MMR) is the cause of microsatellite instability pathway and specifically associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. MMR expression was evaluated in Barrett’s adenocarcinomas. An association between HNPCC and Barrett’s adenocarcinoma may exist, although probably without clinical significance. IV. Increased understanding of the molecular processes associated with Barrett’s carcinogenesis may be beneficial for early tumor detection, refined diagnosis and for improved prognostication. Immunohistochemical staining was applied for tumor markers in order to evaluate their prognostic importance in Barrett’s adenocarcinomas. Reduced expression of E-cadherin was significantly associated with a more advanced tumor stage and was also shown to independently predict a poor prognosis.