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Digestive Diseases and Sciences

, Volume 56, Issue 9, pp 2656–2665 | Cite as

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

  • Lisa Yerian
  • Roberto Fiocca
  • Luca Mastracci
  • Robert Riddell
  • Michael Vieth
  • Prateek Sharma
  • Stefan Franzen
  • Paula Fernstrom
  • Magnus Ruth
Original Article

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.

Keywords

Gastroesophageal reflux Esophagitis Histology Observer variation Consensus 

Notes

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.

References

  1. 1.
    Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–1920.PubMedCrossRefGoogle Scholar
  2. 2.
    Voutilainen M, Sipponen P, Mecklin JP, et al. Gastroesophageal reflux disease: Prevalence, clinical, endoscopic and histopathological findings in 1,128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms. Digestion. 2000;61:6–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Isolauri J, Luostarinen M, Isolauri E, et al. Natural course of gastroesophageal reflux disease: 17–22 year follow-up of 60 patients. Am J Gastroenterol. 1997;92:37–41.PubMedGoogle Scholar
  4. 4.
    Corder AP, Jones RH, Sadler GH, et al. Heartburn, oesophagitis and Barrett’s oesophagus in self-medicating patients in general practice. Br J Clin Pract. 1996;50:245–248.PubMedGoogle Scholar
  5. 5.
    Ronkainen J, Aro P, Storskrubb T, et al. High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: A Kalixanda study report. Scand J Gastroenterol. 2005;40:275–285.PubMedCrossRefGoogle Scholar
  6. 6.
    Zagari RM, Pozzato P, Nicolini G, et al. Prevalence of asymptomatic endoscopic lesions of the upper gastrointestinal tract. Preliminary results of The Loiano-Monghidoro population study. Gastroenterology. 2002;122:A208.Google Scholar
  7. 7.
    Dent J. Microscopic esophageal mucosal injury in nonerosive reflux disease. Clin Gastroenterol Hepatol. 2007;5:4–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Vieth M, Fiocca R, Haringsma J, et al. Radial distribution of dilated intercellular spaces of the esophageal squamous epithelium in patients with reflux disease exhibiting discrete endoscopic lesions. Dig Dis. 2004;22:208–212.PubMedCrossRefGoogle Scholar
  9. 9.
    Vieth M, Peitz U, Labenz J, et al. What parameters are relevant for the histological diagnosis of gastroesophageal reflux disease without Barrett’s mucosa? Dig Dis. 2004;22:196–201.PubMedCrossRefGoogle Scholar
  10. 10.
    Zentilin P, Savarino V, Mastracci L, et al. Reassessment of the diagnostic value of histology in patients with GERD, using multiple biopsy sites and an appropriate control group. Am J Gastroenterol. 2005;100:2299–2306.PubMedCrossRefGoogle Scholar
  11. 11.
    Winter HS, Madara JL, Stafford RJ, et al. Intraepithelial eosinophils: A new diagnostic criterion for reflux esophagitis. Gastroenterology. 1982;83:818–823.PubMedGoogle Scholar
  12. 12.
    Fiocca R, Mastracci L, Riddell R, et al. Development of consensus guidelines for the histologic recognition of microscopic esophagitis in patients with gastroesophageal reflux disease: The Esohisto project. Hum Pathol. 2010;41:223–231.PubMedCrossRefGoogle Scholar
  13. 13.
    Mastracci L, Spaggiari P, Grillo F, et al. Microscopic esophagitis in gastro-esophageal reflux disease: Individual lesions, biopsy sampling, and clinical correlations. Virchows Arch. 2009;454:31–39.PubMedCrossRefGoogle Scholar
  14. 14.
    Lundell L, Attwood S, Ell C, et al. Comparing laparoscopic antireflux surgery with esomeprazole in the management of patients with chronic gastro-oesophageal reflux disease: A 3-year interim analysis of the LOTUS trial. Gut. 2008;57:1207–1213.PubMedCrossRefGoogle Scholar
  15. 15.
    Haas M. The reliability of reliability. J Manipulative Physiol Ther. 1991;14:199–208.PubMedGoogle Scholar
  16. 16.
    Behar J, Sheahan D. Histologic abnormalities in reflux esophagitis. Arch Pathol. 1975;99:387–391.PubMedGoogle Scholar
  17. 17.
    Ismail-Beigi F, Horton PF, Pope CE 2nd. Histological consequences of gastroesophageal reflux in man. Gastroenterology. 1970;58:163–174.PubMedGoogle Scholar
  18. 18.
    Groben PA, Siegal GP, Shub MD, et al. Gastroesophageal reflux and esophagitis in infants and children. Perspect Pediatr Pathol. 1987;11:124–151.PubMedGoogle Scholar
  19. 19.
    Cooper HS, Dayal Y, Gourley WK, et al. Proceedings of the 1988 Subspecialty Conference on Gastrointestinal Pathology at the USCAP. United States and Canadian Academy of Pathology. Diagnostic nonproblems in gastrointestinal biopsy pathology. Mol Pathol. 1989;2:244–259.Google Scholar
  20. 20.
    Mitros FA. Atlas of gastrointestinal pathology. Philadelphia: Lippincott; 1988:1.2–1.12.Google Scholar
  21. 21.
    Sternberg SS. Histology for pathologists. 2nd ed. Philadelphia: Lippincott; 1997:468.Google Scholar
  22. 22.
    Vieth M, Haringsma J, Delarive J, et al. Red streaks in the oesophagus in patients with reflux disease: Is there a histomorphological correlate? Scand J Gastroenterol. 2001;36:1123–1127.PubMedCrossRefGoogle Scholar
  23. 23.
    Villanacci V, Grigolato PG, Cestari R, et al. Dilated intercellular spaces as markers of reflux disease: Histology, semiquantitative score and morphometry upon light microscopy. Digestion. 2001;64:1–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Solcia E, Villani L, Luinetti O, et al. Altered intercellular glycoconjugates and dilated intercellular spaces of esophageal epithelium in reflux disease. Virchows Arch. 2000;436:207–216.PubMedCrossRefGoogle Scholar
  25. 25.
    Feinstein AR, Cicchetti DV. High agreement but low kappa: I. The problems of two paradoxes. J Clin Epidemiol. 1990;43:543–549.PubMedCrossRefGoogle Scholar
  26. 26.
    Cicchetti DV, Feinstein AR. High agreement but low kappa: II. Resolving the paradoxes. J Clin Epidemiol. 1990;43:551–558.PubMedCrossRefGoogle Scholar
  27. 27.
    Collins BJ, Elliott H, Sloan JM, et al. Oesophageal histology in reflux oesophagitis. J Clin Pathol. 1985;38:1265–1272.PubMedCrossRefGoogle Scholar
  28. 28.
    Grønbaek K, Christensen PB, Hamilton-Dutoit S, et al. Interobserver variation in interpretation of serial liver biopsies from patients with chronic hepatitis C. J Viral Hepat. 2002;9:443–449.PubMedCrossRefGoogle Scholar
  29. 29.
    el-Zimaity HM, Graham DY, al-Assi MT, et al. Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis. Hum Pathol. 1996;27:35–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Offerhaus GJ, Price AB, Haot J, et al. Observer agreement on the grading of gastric atrophy. Histopathology. 1999;34:320–325.PubMedCrossRefGoogle Scholar
  31. 31.
    Hsu PI, Lai KH, Tseng HH, et al. Risk factors for presentation with bleeding in patients with Helicobacter pylori-related peptic ulcer diseases. J Clin Gastroenterol. 2000;30:386–391.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Lisa Yerian
    • 1
  • Roberto Fiocca
    • 2
  • Luca Mastracci
    • 2
  • Robert Riddell
    • 3
  • Michael Vieth
    • 4
  • Prateek Sharma
    • 5
  • Stefan Franzen
    • 6
  • Paula Fernstrom
    • 6
  • Magnus Ruth
    • 6
  1. 1.Department of Anatomic Pathology, L-25Cleveland ClinicClevelandUSA
  2. 2.Department of Anatomic PathologyUniversity of GenoaGenoaItaly
  3. 3.Department of PathologyMount Sinai HospitalTorontoCanada
  4. 4.Institute of PathologyKlinikum BayreuthBayreuthGermany
  5. 5.Division of Gastroenterology and HepatologyUniversity of Kansas School of MedicineKansas CityUSA
  6. 6.AstraZeneca R&DMölndalSweden

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