Proposed approach to the challenging management of progressive gastroesophageal reflux disease

Abstract

The progression of gastroesophageal reflux disease (GERD) in patients who are taking proton pump inhibitors (PPIs) has been reported by several investigators, leading to concerns that PPI therapy does not address all aspects of the disease. Patients who are at risk of progression need to be identified early in the course of their disease in order to receive preventive treatment. A review of the literature on GERD progression to Barrett's esophagus and the associated physiological and pathological changes was performed and risk factors for progression were identified. In addition, a potential approach to the prevention of progression is discussed. Current evidence shows that GERD can progress; however, patients at risk of progression may not be identified early enough for it to be prevented. Biopsies of the squamocolumnar junction that show microscopic intestinalization of metaplastic cardiac mucosa in endoscopically normal patients are predictive of future visible Barrett's esophagus, and an indicator of GERD progression. Such changes can be identified only through biopsy, which is not currently recommended for endoscopically normal patients. GERD treatment should aim to prevent progression. We propose that endoscopically normal patients who partially respond or do not respond to PPI therapy undergo routine biopsies at the squamocolumnar junction to identify histological changes that may predict future progression. This will allow earlier intervention, aimed at preventing Barrett's esophagus.

Keywords: Barrett’s esophagus; Endoscopy; Gastroesophageal reflux disease; Progression; Treatment.

Figure 1

Retroflex endoscopic view of the squamocolumnar junction in advanced gastroesophageal reflux disease. A: Normal white light image displays a slightly irregular SCJ with normal squamous epithelium extending up the esophagus; B: Narrow band image shows multiple islands of squamous epithelium below the SCJ, surrounded by newly formed metaplastic cardiac epithelium. The splayed out original SCJ (indicated by the yellow line), and damaged portion of the LES between the original SCJ and the current SCJ, take on the appearance of stomach. Loss of esophageal muscle due to inflammation results in a reduction in the abdominal length of the LES and loss of the LES barrier function. Images used with permission from Dr. Peters, Case Western University, Cleveland, OH, United States. GERD: Gastroesophageal reflux disease; LES: Lower esophageal sphincter; SCJ: Squamocolumnar junction.

Figure 2

Effacement of the lower esophageal sphincter as a result of gastric distension or dilation. Exposure of the squamous mucosa covering the effaced portion of the LES to gastric juice results in inflammation, the formation of metaplastic cardiac mucosa, and progressive loss of LES length. The red line represents the squamous epithelial covering of the effaced portion of the LES (in black) as it is taken up by the expanding gastric fundus. LES: Lower esophageal sphincter.

Figure 3

The histology of the squamo-oxyntic gap. A: The normal junction of the esophagus and stomach is the abutment of the proximal limit of the gastric oxyntic epithelium and the distal limit of the squamous epithelium; B: Squamo-oxyntic gap: Squamous epithelium is replaced by metaplastic cardiac mucosa resulting in loss of LES length, as shown by manometry. Images provided by Dr. Parakrama Chandrasoma. GEJ: Gastroesophageal junction; GERD: Gastroesophageal reflux disease; LES: Lower esophageal sphincter; SCJ: Squamocolumnar junction.

Figure 4

Proposed algorithm for the treatment of patients with progressive gastroesophageal reflux disease. Patients who do not respond to PPI therapy and who have an abnormal 24-h esophageal pH should undergo endoscopy. Patients can be stratified into four groups following endoscopy: (1) patients with visible BE; (2) patients with persistent esophagitis; (3) patients with a normal endoscopy who have microscopic IM of the SCJ; and (4) patients with a normal endoscopy who have carditis at the SCJ. Patients in groups (2), (3) and (4) should undergo manometric assessment of LES function; those with a defective LES may be candidates for LES augmentation. ¹If more than 2 permanently defective LES components consider Nissen fundoplication. BE: Barrett’s esophagus; GERD: Gastroesophageal reflux disease; LES: Lower esophageal sphincter; IM: Intestinal metaplasia; PPI: Proton pump inhibitor; SCJ: Squamocolumnar junction.