How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

Abstract

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.

Intercellular Space Volume Is Mainly Increased in the Basal Layer of Esophageal Squamous Epithelium in Patients with GERD

“…ions to penetrate into the deeper layers and submucosal [11,12]. Furthermore, it is possible that the impairment of the esophagus begins in the deeper parts, caused by various chemokines affecting multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands [26]. This again could be a reason for the missing alteration of DIS in patients with BE.…”

Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett’s Esophagus

“…Since EAC is frequently detected at an advanced stage, the prognosis of patients with advanced EAC is still poor, with a 5-year overall survival rate of 10-20% [1,2]. Barrett's esophagus is a premalignant condition of the distal part of the esophagus in which normal squamous epithelium is replaced by columnar-lined epithelium with characteristic goblet cells [3]. Both chronic inflammation and ongoing exposure to an acid and bile containing gastroesophageal refluxate are considered to be important pathogenic factors in the development of BE and EAC [3][4][5].…”

“…Barrett's esophagus is a premalignant condition of the distal part of the esophagus in which normal squamous epithelium is replaced by columnar-lined epithelium with characteristic goblet cells [3]. Both chronic inflammation and ongoing exposure to an acid and bile containing gastroesophageal refluxate are considered to be important pathogenic factors in the development of BE and EAC [3][4][5]. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation associated carcinogenesis [6][7][8][9][10].…”

hERG1 channels in human esophagus: Evidence for their aberrant expression in the malignant progression of Barrett's esophagus

“…BE is an acquired condition that results from GERD and is characterized by the metaplastic replacement of the normal squamous epithelium of the lower esophagus, up to the squamocolumnar junction (also known as Z line), by a columnar, intestinal-like, epithelium (Spechler, 2002). In other words, when defence mechanisms in esophageal mucosa are chronically overwhelmed by harmful agents, BE develops as a healing process protecting the esophagus from further damage (Guillem, 2005). BE is a premalignant condition that predisposes to the development of esophageal adenocarcinoma (Haggitt and Dean, 1985), atumor with an increasing frequency in most western countries (Newnham et al, 2003).…”