Molecular Changes at the Esophagogastric Junction (EGJ) in Patients with Symptomatic Gastroesophageal Reflux Disease (GERD) in the Absence of Histological Columnar Metaplasia (CM)

Abstract Has a histologic transition from gastroesophageal reflux disease–damaged epithelium to columnar metaplasia ever been seen in humans? The answer to this question seems to be that it has but that we either do not readily recognize it or it is not readily recognizable with regular light microscopy. There are at least 3 possible mechanisms for the genesis of Barrett esophagus. The first is ulceration at the gastroesophageal junction with subsequent repair by an epithelium that differentiates into Barrett epithelium. The second is metaplasia through multilayered epithelium. The third is creeping columnar metaplasia at the Z-line proximally followed by intestinalization. These 3 hypotheses may not be mutually exclusive, and all may be operative, depending on the local circumstances, amount of inflammation, erosion, ulcers, healing, acid and alkaline reflux, and use of proton pump inhibitors. Any of the epithelial types involved could be stable and not progress. They might even be reversible, which may also in part explain the mosaic of epithelial types that typify Barrett esophagus, and may be modified by any of the molecular mechanisms that turn protein transcription on and off (eg, promoter methylation, mutations). These mechanisms ultimately may also be involved in the genesis of neoplastic transformation.

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Esophagogastric junction distensibility: a factor contributing to sphincter incompetence

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00279.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. G1052-G1058 ◽

Cited By ~ 96

Author(s):

John E. Pandolfino ◽

Guoxiang Shi ◽

Jennifer Curry ◽

Raymond J. Joehl ◽

James G. Brasseur ◽

...

Keyword(s):

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Lower Esophageal Sphincter ◽

Hiatus Hernia ◽

Reflux Disease ◽

Esophagogastric Junction ◽

Normal Subjects ◽

Opening Pressure ◽

Esophageal Sphincter

To quantify the effect of hiatus hernia (HH) on esophagogastric junction (EGJ) distensibility, eight normal subjects and nine gastroesophageal reflux disease (GERD) patients with HH were studied with concurrent manometry, fluoroscopy, and stepwise controlled barostatic distention of the EGJ. The minimal barostatic pressure required to open the EGJ during the interswallow period was determined. Thereafter, barium swallows were imaged in 5-mmHg increments of intrabag pressure. EGJ diameter and length were measured at each pressure during deglutitive relaxation. The EGJ opening diameter was greater in hernia patients compared with normal subjects during deglutitive relaxation at all pressures, and EGJ length was 23% shorter. EGJ opening pressure among hernia patients was lower than normal subjects during the interswallow period. In conclusion, the EGJ of GERD patients with HH was more distensible and shorter than normal subjects. These findings partially explain why HH patients are predisposed to reflux by mechanisms other than transient lower esophageal sphincter relaxations, sustain greater volumes of refluxate, and have a reduced ability to discriminate gas from liquid reflux.

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