Barrett’s Esophagus Revisited: Epidemiology, Risk Stratification and Cancer Prevention

Cancer of the esophagus (EAC) is a highly aggressive malignancy worldwide, of which the incidence has increased tremendously during the last decades. Barrett’s esophagus (BE) is the only recognized precursor lesion and is associated with the majority, if not all, cases with adenocarcinoma. BE predisposes to the development of EAC, following a multi-step cascade through stages of esophagitis, intestinal metaplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), to invasive adenocarcinoma. Endoscopic screening of subjects with chronic gastro-esophageal reflux symptoms has been proposed as a method for detecting BE. Once BE has been diagnosed, surveillance endoscopy is advised at intervals based on the presence or absence and grade of dysplasia, in order to detect early stage cancers suitable for curative treatment, and ultimately to prevent deaths from EAC. Unfortunately, the efficacy of screening and surveillance of BE remains a strongly debated issue, as there are many unresolved epidemiological dilemmas, of which the inability to predict who has BE prior to endoscopy, and the lack of data on the natural history of BE are the major ones. Improved risk stratification could improve the effectiveness of screening and surveillance in BE patients, and achieve the ultimate goal of reducing EAC mortality. The aim of the studies described in this thesis is to reassess the yield of screening for and surveillance of BE in the prevention of EAC, by exploring the natural course of BE, by investigating various risk factors involved in the progression of chronic gastro-esophageal reflux disease to BE and finally to HGD or EAC, and by examining the value of non-invasive techniques in the identification of high risk groups.

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