The incidence of esophageal adenocarcinoma (EAC) has increased exponentially in the last 3 decades. Barrett’s esophagus (BE) is the only known precursor of EAC. Patients with BE have a greater than 40 folds higher risk of EAC compared with the general population. Recent years have witnessed a revolution in the clinical and molecular research related to BE. However, several aspects of this condition remain controversial. Data regarding the true prevalence of BE have varied widely. Recent studies have suggested a lower incidence of EAC in nondysplastic BE (NDBE) than previously reported. There is paucity of prospective data showing a survival benefit of screening or surveillance for BE. Furthermore, the ever-increasing emphasis on healthcare cost containment has called for reexamination of the screening and surveillance strategies for BE. There is a need for identification of reliable clinical predictors or molecular biomarkers to risk-stratify patients who might benefit the most from screening or surveillance for BE. Finally, new therapies have emerged for the management of dysplastic BE. In this paper, we highlight the key areas of controversy and uncertainty surrounding BE. The paper discusses, in detail, the current literature about the molecular pathogenesis, biomarkers, histopathological diagnosis, and management strategies for BE. 1. Introduction In the last 3 decades, the incidence of esophageal adenocarcinoma (EAC) has increased at a faster rate than any other cancer in the US and Western Europe [1–4]. Despite advances in therapies, the 5-year survival rate for EAC remains less than 15% [5]. Barrett’s esophagus (BE), a condition in which the squamous epithelium of the distal esophagus is replaced by columnar epithelium with intestinal metaplasia (IM), is a well-established precursor of EAC. BE increases the risk of EAC by greater than 40-fold compared with the general population [6, 7]. Our understanding of BE has increased significantly over the past half a century. However, many aspects of the natural history and pathophysiology of BE have not been fully elucidated. Some of the controversial areas of BE include the following:(i)There is a lack of consensus regarding the definition of BE and whether IM should be a requirement for the diagnosis of BE [8–10].(ii)True prevalence of BE in the general population and its risk of progression to EAC remain unclear. Recent studies have suggested a lower risk of malignant transformation of BE than previously reported [11–14].(iii)A clear survival benefit of screening or surveillance for BE has not been
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