Effects of Long-term Treatment with Proton Pump Inhibitors in Gastro-oesophageal Reflux Disease on the Histological Findings in the Lower Oesophagus

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Abstract
Background: The application of hyperplasia of the basal cell layer and elongation of the papillae in the squamous epithelium of the distal oesophagus, as histological criteria for the diagnosis of gastro-oesophageal reflux disease (GORD), continues to be controversial. An unanswered question is whether these changes may regress under long-term treatment with proton pump inhibitors (PPI). This fact prompted us to investigate the effect of PPI treatment on the histological changes observed in the lower oesophagus. Methods: 295 patients with endoscopically confirmed erosive GORD were investigated by endoscopy/biopsy prior to and during the course of a 12-month PPI treatment regimen (8 weeks acute treatment with 30 mg lansoprazole/day followed by long-term treatment with 15 or 30 mg lansoprazole or 20 mg omeprazole/day). The parameters studied were the frequency of ulcers and erosions and the hyperplasia of the basal cell layer and elongation of the papillae prior to treatment and on day 56 (D56), after 6 months (M6) and after 12 months (M12) of treatment. Results: In the various treatment groups, the results showed no statistically significant differences. Ulcers and erosions (prior to treatment 21% and 31%, respectively) were detected statistically significantly less frequently under PPI treatment (ulcers, D56: 1%, M6 and M12, 0%; erosions, D56: 2%, M6: 4%, M12, 3%). While high-grade hyperplasia of the basal cell layer and elongation of the papillae was found in 51% of the cases prior to treatment, the corresponding figures were only 3% (D56, M6) and 2% (M12). In contrast, the percentage of cases with normal oesophageal epithelium increased from 8% before treatment to 55% (D56), 66% (M6) and 63% (M12). Conclusions: Our study shows not only that erosions and ulcers heal under PPI treatment, but also that hyperplasia of the basal cell layer and elongation of papillae in the squamous epithelium of the oesophageal mucosa may normalize, and are thus presumably not 'normal physiological variants'.