These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia. PURPOSE AND METHODSThe purpose of this guideline is to provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. This document is therefore aimed at gastroenterologists, physicians and nurse practitioners, as well as members of multidisciplinary teams (MDTs; surgeons, radiologists, pathologists), who take decisions on the management of such patients. The population covered by these guidelines includes: patients with gastrooesophageal reflux disease or other risk factors for Barrett's (obesity, family history for Barrett's and oesophageal adenocarcinoma (OAC)); every patient with incident or prevalent Barrett's oesophagus regardless of their age, sex or comorbidities; patients with early OAC and patients with intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ) with no endoscopic evidence of Barrett's oesophagus. The previous British Society of Gastroenterology (BSG) development of the guidelines and to aid assessment of the quality of the guidelines. Three appraisers in the author list assessed the compliance of the guidelines to the AGREE II domains. As part of the AGREE II criteria, external review of this manuscript was also performed by two internationally renowne...

The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range 20 to 75 years). Somatic mutations accumulated with age and were mainly caused by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and ageing.