28 Factors such as these might place particular individuals in a “double trouble” situation at greater risk for mucosal healing with columnar metaplasia. The key drivers of the development of dysplasia and EA are unknown. Thinking about likely candidates is currently dominated by the assumption that the hostile esophageal luminal environment in BE patients is a key factor in triggering development of dysplasia and EA.4,26 This paradigm is challenged by the lack of evidence, discussed in more detail later, that major alteration of the luminal environment by therapy is associated with

any detectable protection against development of EA. This is most convincing in the case of antireflux surgery.29,30 It does not necessarily follow that because a hostile luminal environment is important in causing the development of BE click here that this also drives ABT-199 price development of EA. It seems more likely that the stability of the mucosa in BE is inherently

impaired and that extra-luminal factors such as genetic polymorphisms or being iron-replete could play a more important part in driving EA development than the esophageal luminal environment.4 The ongoing BOSS study offers hope for better definition of factors that drive malignant change in BE.31 This is a huge but well-informed fishing trip in which many variables of possible importance to EA development are being measured in an unprecedented number of BE patients, including those involved in the AspECT study17 (see the section on chemoprevention below). Evaluation of samples includes a genome-wide analysis. Endoscopy remains the only practical option for the routine diagnosis and assessment of esophageal

columnar metaplasia. Despite major technical developments of equipment over the last 20 years, the first steps of endoscopic assessment—the recognition of BE and the grading of its extent—remain a major source of inaccuracy. The first systematic study on the endoscopic recognition of BE, which was carried out by the International Working Group for the Classification of Oesophagitis (IWGCO), resulted in the Prague C & M Criteria.32 These were developed in the light of structured evaluations of the interpretation of purpose-recorded and standardized endoscopic video recordings. The Pyruvate dehydrogenase lipoamide kinase isozyme 1 Prague Criteria, illustrated in Fig. 3, have already been widely adopted; they highlight the pivotal first step of the endoscopic diagnosis of BE- the correct determination of the position of the anatomical junction between the stomach and esophagus, a judgment that has bedeviled this field since before Norman Barrett was a schoolboy! The best performing landmark, the position of the tops of the gastric mucosal folds during only modest filling of the stomach and esophagus with air was chosen to define the position of the gastroesophageal junction.