Hostile environment of the gastroesophageal junction

The gastroesophageal junction is remarkable for its high prevalence of mucosal pathology including inflammation, erosions, metaplasia, and adenocarcinoma. The incidence of disease focused at this site has increased in the West over recent decades and this has coincided with a decline in Helicobacter pylori infection and atrophic gastritis. This is consistent with most disease at the gastroesophageal junction being due to damage by refluxing acidic gastric juice. Several observations may explain the focusing of mucosa pathology at the gastroesophageal junction. Recent studies have demonstrated much greater acid exposure of the esophageal squamous mucosa near to the gastroesophageal junction than at 7-cm proximal to this where acid reflux has been traditionally measured. The mechanism of this short segment reflux is unclear but it is likely to be relevant to the high incidence of pathology affecting the most distal esophagus and in asymptomatic subjects. In addition, it has been recognized that the proximal cardia region of the stomach largely escapes the buffering effect of food and remains highly acidic after meals. This unbuffered acid pocket will be available for refluxing into the esophagus during the postprandial reflux when transient lower esophageal relaxations are most frequent. The gastroesophageal junction is also where saliva meets acidic gastric juice and this results in very active and potentially mutagenic luminal nitrosative chemistry. This arises from the reaction between the high concentrations of nitrite in saliva and the hydrochloric acid and ascorbic acid in gastric juice. The gastroesophageal junction is thus a site of very active chemical warfare, the primary function of which is to destroy potentially pathogenic ingested microorganisms. However, as with all legitimate targets, there is always a risk of collateral damage.