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Refinement and Reproducibility of Histologic Criteria for the Assessment of Microscopic Lesions in Patients with Gastroesophageal Reflux Disease: the Esohisto Project

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Abstract

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.

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Acknowledgments

We thank Aperio Technologies Inc., Vista, California, USA, for scanning the biopsy specimen slides and for providing the digital pathology management software. We gratefully acknowledge Dr. Kaiyo Takubo for his role in helping to develop and test the histologic criteria in this study. AstraZeneca R&D, Mölndal, Sweden, provided economic support for the travel, logistics, and statistical analysis. Writing assistance funded by AstraZeneca R&D, Mölndal, Sweden, was provided by Dr. Anja Becher and Dr. Michael Molloy-Bland from Oxford PharmaGenesis.

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Authors and Affiliations

  1. Department of Anatomic Pathology, L-25, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Lisa Yerian

  2. Department of Anatomic Pathology, University of Genoa, Via De Toni 14, 16132, Genoa, Italy

    Roberto Fiocca & Luca Mastracci

  3. Department of Pathology, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada

    Robert Riddell

  4. Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Strasse 101, 95445, Bayreuth, Germany

    Michael Vieth

  5. Division of Gastroenterology and Hepatology, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA

    Prateek Sharma

  6. AstraZeneca R&D, 431 83, Mölndal, Sweden

    Stefan Franzen, Paula Fernstrom & Magnus Ruth

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  1. Lisa Yerian
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  2. Roberto Fiocca
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Correspondence to Lisa Yerian.

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Yerian, L., Fiocca, R., Mastracci, L. et al. Refinement and Reproducibility of Histologic Criteria for the Assessment of Microscopic Lesions in Patients with Gastroesophageal Reflux Disease: the Esohisto Project. Dig Dis Sci 56, 2656–2665 (2011). https://doi.org/10.1007/s10620-011-1624-z

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  • DOI: https://doi.org/10.1007/s10620-011-1624-z

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