Refinement and reproducibility of histologic criteria for the assessment of microscopic lesions in patients with gastroesophageal reflux disease: the Esohisto Project.

BACKGROUND: Standardized criteria for assessing microscopic esophageal lesions are required to test their utility as markers of gastroesophageal reflux disease (GERD). AIMS: To finalize draft criteria for assessing microscopic esophageal lesions associated with gastroesophageal reflux and to test them for interobserver agreement. METHODS: An international group of gastrointestinal pathologists was convened to finalize, using a consensus-based approach, draft criteria for recognizing microscopic esophageal lesions. Finalized criteria were retested for interobserver variability by four of the pathologists using 120 digitized esophageal biopsy slides from patients with GERD. RESULTS: The finalized criteria included further clarification on lesion definitions and new guidance on how to select the area for assessing each lesion. This latter refinement was guided by the high interobserver agreement observed when draft criteria were previously applied to biopsies where the assessment area was preselected. When finalized criteria were applied in the current study to digitized biopsies without a preselected assessment area, the pairwise agreement was 73-97% for basal cell hyperplasia, papillary elongation, intraepithelial eosinophil, neutrophil and mononuclear cell numbers, and active/healed erosions, with slightly lower agreement (64%) for dilated intercellular spaces (DIS). When a combined severity score was applied, the level of agreement was 77%. The mean kappa ranged from fair to high (0.26-0.77) for individual lesions and was high for the combined score (0.64). CONCLUSIONS: These levels of agreement are comparable with or higher than those for other accepted histologic definitions. Further steps include clinical validation of these criteria by correlating microscopic lesions with clinical variables such as esophageal acid exposure.

Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: the Esohisto project.

No gold standard test exists for gastroesophageal reflux disease (GERD). Diagnostic difficulties are greatest when reflux symptoms occur without visible esophageal mucosal damage at conventional endoscopy. However, two thirds of such patients do have microscopic esophageal lesions. This study aimed to develop and standardize criteria for recognizing these microscopic esophageal lesions in GERD. Draft histologic criteria were developed and tested by an international group of 5 independent gastrointestinal pathologists using 167 biopsy specimens from GERD patients and healthy controls (phase I). Draft criteria were refined and reassessed using 250 photographs of biopsy specimens (phase II). Histologic lesions evaluated were basal cell hyperplasia, papillary elongation, intraepithelial eosinophil, neutrophil and mononuclear cell number, necrosis/erosion, healed erosion, and dilated intercellular spaces. Interobserver agreement and kappa values increased significantly from phase I to II. When tested in annotated photographs (phase II), mean pairwise agreements were 74%, 89%, 93%, 97%, 81%, 97%, 94%, and 74%, respectively. Mean pairwise kappa estimates (+/-SD) were 0.49 (0.16), 0.81 (0.05), 0.87 (0.05), 0.84 (0.09), 0.60 (0.09), 0.90 (0.04), 0.73 (0.14), and 0.61 (0.08), respectively. Estimated intraclass correlation coefficients for basal cell layer thickness and papillary length increased from 0.38 and 0.56 to 0.69 and 0.95, respectively, when revised criteria were used. The draft criteria achieved promising levels of agreement when assessed independently by 5 pathologists. Further steps include evaluation of lesions without indicating the area to be assessed and exploring the correlation of microscopic esophagitis with symptoms and esophageal acid exposure.

Occurrence of nighttime gastroesophageal reflux in disturbed and normal sleepers.

BACKGROUND & AIMS: It is not uncommon in a sleep laboratory to encounter individuals who have complaints of disturbed sleep, but who do not meet the criteria for a sleep disorder when evaluated by polysomnography. Because gastroesophageal reflux is known to occur in many individuals without their awareness, it is possible that some of these individuals might be suffering from reflux that is disturbing their sleep. METHODS: Eighty-one individuals with complaints of disturbed or unrefreshing sleep, but no complaints of heartburn, were recruited. A comparison group of 39 individuals with neither sleep nor heartburn complaints also was studied. Both groups were studied on 2 separate occasions by simultaneous polysomnography and pH monitoring to detect the presence of nighttime gastroesophageal reflux and to determine sleep outcomes. RESULTS: In the disturbed-sleep group 27% of subjects had at least one reflux event compared with 33% in the normals. In the subjects who experienced reflux, the disturbed-sleep group had a significantly greater percentage of acid exposure time compared with the normals (9.5% vs 1.6%; P < .05). Participants in the disturbed-sleep group also had a longer sleep-onset latency (P < .05) and less total sleep time (P < .05) compared with the normal sleepers. CONCLUSIONS: Among individuals with complaints of disturbed sleep, there was a subset of individuals who had significant gastroesophageal reflux. We speculate that sleep-related gastroesophageal reflux may play a role in producing disturbed sleep in individuals without heartburn and otherwise unexplained sleep disturbance.