Evaluation of Histologic Criteria for the Diagnosis of Gastroesophageal Reflux Disease

Abstract

Background. Standardized criteria for the histologic assessment of gastroesophageal reflux disease (GERD) were recently developed and evaluated by an international working group, and showed promising levels of intraand inter-assessor agreement1. To gain clinical acceptance these criteria require appropriate validation2.Aim. To evaluate new criteria for histologic markers of GERD in a well characterized primary care population. Methods. The study included primary care patients from the Diamond study3 (ClinicalTrials.gov: NCT00291746) who had not previously taken proton pump inhibitors and who had upper gastrointestinal symptoms ≥ 2 times a week for ≥ 4 weeks, and at least mild symptoms on ≥ 3 days in the week before biopsy. GERD was diagnosed as any of the following: Los Angeles grade reflux esophagitis; distal esophageal pH 5.5% of 24 hours; ≥ 95% symptom association probability. Biopsies were collected at 0.5 cm and 2.0 cm above the Z-line and data were analyzed in a single-blind manner by one pathologist (MV). Variables assessed included total epithelial thickness (TET), papillary length (PL), basal cell thickness (all in μm), presence of dilated intercellular spaces (severity score: 0-2)1, number of inflammatory cells (in one high powered field), presence of necrosis, and presence of active or healed erosions. Logistic regression analysis of the histologic variables was performed for GERD versus non-GERD. Cut-off values for sensitivity, specificity, and predictive power (positive and negative) were calculated, and the receiver operating characteristic (ROC) curve was analyzed. Results. The analysis included 258 subjects: 138 (53%) GERD and 120 (47%) non-GERD. TET and PL (μm) at 0.5 cm and 2.0 cm were both significant predictors of GERD (p < 0.005), as was the presence of eosinophils at 2.0 cm (p < 0.05). The optimal efficiency based on the ROC analysis was observed for TET at 0.5 cm, with sensitivity and specificity values of 77% and 52%, and positive and negative predictive values of 65% and 66%, based on a cut-off of 390 μm. TET and PL were significant (p < 0.05) predictors of both reflux esophagitis and of pathologic esophageal pH. TET and PL were also significant predictors (p < 0.05) of non-erosive reflux disease versus non-GERD. Conclusions. Potential new criteria for the histologic evaluation of GERD showed good diagnostic properties when assessed in a well-characterized primary care population with upper gastrointestinal symptoms.