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- BARRETT'S OESOPHAGUS
- BARRETT'S METAPLASIA
- GASTRO-OESPHAGEAL JUNCTION
- OESOPHAGEAL PHYSIOLOGY
- OESOPHAGEAL REFLUX
The pathogenesis of adenocarcinoma of the oesophagus is assumed to start with GORD that damages the oesophageal squamous epithelium while also inducing genetic reprogramming of progenitor cells that proliferate to repair the damage.1 Presumably, this GORD-induced reprogramming of developmental transcription factors causes the progenitors to differentiate into columnar cells with intestinal features, resulting in the squamous-to-columnar metaplasia of Barrett's oesophagus. Barrett's metaplasia, in an environment of oxidative and nitrosative stress from ongoing GORD, is predisposed to develop further genetic alterations resulting in dysplasia and, ultimately, cancer. Thus, oesophageal adenocarcinoma is widely regarded as a consequence of GORD and Barrett's oesophagus in most, if not all cases.
A number of observations have been difficult to reconcile with this popular concept of oesophageal carcinogenesis. Most notably, many patients with oesophageal adenocarcinoma have no evidence of antecedent GORD or Barrett's metaplasia.2 ,3 Rather than abandoning the notion that all oesophageal adenocarcinomas arise from GORD and Barrett's oesophagus, authorities have proposed explanations for the unsupportive observations. The lack of antecedent GORD symptoms can be attributed to poor patient recall or to GORD that causes oesophageal damage without symptoms. The absence of Barrett's metaplasia in the oesophagus of patients with established adenocarcinomas has been dismissed as a consequence of tumour growth obliterating evidence of the precursor metaplasia. Although plausible, these explanations are largely unprovable and highly questionable.
In the stomach, chronic gastritis can lead to adenocarcinoma that is histologically indistinguishable from oesophageal adenocarcinoma. For an adenocarcinoma that straddles the gastro-oesophageal junction (GOJ), therefore, it is often not possible to establish whether the tumour arose from oesophagus or stomach. Consequently, patients with …
Competing interests SJS has served as a consultant for Takeda Pharmaceuticals, Ironwood Pharmaceuticals and Interpace Diagnostics.
Provenance and peer review Commissioned; internally peer reviewed.
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