Barrett esophagus: an update

Abstract

Many developments have been made in the field of Barrett esophagus that have tremendous clinical implications. There are new definitions of Barrett esophagus that have had an immediate clinical impact on cancer risk and screening. Of interest is the definition by the British Society of Gastroenterology, which does not require the presence of intestinal metaplasia for a diagnosis of Barrett esophagus. Imaging techniques that allow improved visualization of intestinal metaplasia at the cellular level are now being used in clinical practice. New hypotheses elucidating the progression from squamous epithelium to intestinal metaplasia have been proposed. Indeed, the crucial role that transcription factors have in the pathogenesis of Barrett esophagus has been clarified. Improved characterization of the molecular mechanisms underlying Barrett esophagus is an incentive to undertake more basic science research in this field. Such research could also help with the development of chemoprevention strategies for this precancerous condition. This Review discusses the advances in understanding of the pathogenesis, diagnosis and treatment of Barrett esophagus.

Boundaries, junctions and transitions in the gastrointestinal tract

“…In mice the squamous epithelium extends into the dome of the stomach, pushing the boundary between stratified and columnar epithelia caudally, into the stomach (Figure 1). This boundary is important clinically because in humans it is the site of a precancerous condition known as Barrett’s metaplasia, wherein squamous tissue in the distal esophagus takes on the appearance and gene expression profile of intestine-type columnar cells (reviewed in [2]). Similar metaplasia often precedes cancer in the distal stomach but is rare elsewhere in the gut, suggesting that the esophagus-stomach boundary and diseased stomach epithelium retain an unusual degree of plasticity in fate.…”

Barrett's metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor

“…Several theories attempt to explain the cellular origins of Barrett's metaplasia: reflux mediated reprogramming of a resident squamous stem cell, stem cell migration from the gastric cardia in order to repopulate the damaged oesophageal mucosa or stem cells within submucosal ducts or glands regenerating the surface epithelium 6 7. A recent study gives precedence to the theory that Barrett's metaplasia arises from cells at the squamocolumnar junction (SCJ)8; in this study, p63 knockout mice were shown to develop a Barrett's-like metaplasia in the squamous fore-stomach, and retrograde growth of a population of Car4-expressing cells located at the SCJ was proposed as the origin of the metaplasia although no lineage tracing was performed.…”

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

“…15 Increased BMP4 expression has been observed in esophagitis and Barrett's esophagus where BMP4 induces the metaplastic transformation of squamous epithelial cells to columnar cells. 16 These examples indicate that BMP4 clearly has a specific role in various processes in adult tissues and organs although comprehensive data on this issue are currently lacking.…”