Development and validation of confocal endomicroscopy diagnostic criteria for low-grade dysplasia in Barrett’s esophagus

Massimiliano di Pietro, Helga Bertani, Maria O'Donovan, Patricia Santos, Hani Alastal, Richard Phillips, Jacobo Ortiz-Fernandez-Sordo, Marietta Iacucci, Ines Modolell, Luca Reggiani Bonetti, Krish Ragunath, Lorenz Wernisch

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Background: Low-grade dysplasia (LGD) in Barrett’s esophagus (BE) is generally inconspicuous on conventional and magnified endoscopy. Probe-based confocal laser endomicroscopy (pCLE) provides insight into gastro-intestinal mucosa at cellular resolution. We aimed to identify endomicroscopic features and develop pCLE diagnostic criteria for BE-related LGD.

Methods: This was a retrospective study on pCLE videos generated in two prospective studies. In Phase I, two investigators assessed 30 videos to identify LGD endomicroscopic features, which were then validated in an independent video set (n=25). Criteria with average accuracy >80% and interobserver agreement κ>0.4 were taken forward. In Phase II, 6 endoscopists evaluated the criteria in an independent video set (n=37). The area under receiver operating characteristic (AROC) curve was constructed to find the best cut-off. Sensitivity, specificity, interobserver and intraobserver agreement were calculated.

Results: In Phase I 6 out of 8 criteria achieved the agreement and accuracy thresholds (i. dark non-round glands, ii. irregular gland shape, iii. lack of goblet cells, iv. sharp cut-off of darkness, v. variable cell size and vi. cellular stratification). The best cut-off for LGD diagnosis was 3 out of 6 positive criteria. In Phase II, the diagnostic criteria had a sensitivity and specificity for LGD of 81.69% and 6774.6%, respectively, with an AROC of 0.860888. The interobserver agreement was substantial (κ= 0.631654) and the mean intraobserver agreement was moderate (κ= 0.590).

Conclusions: We have generated and validated pCLE criteria for LGD in BE. Using these criteria, pCLE diagnosis of LGD is reproducible and has substantial interobserver agreement.
Original languageEnglish
JournalClinical and Translational Gastroenterology
Issue number4
Publication statusPublished - 11 Apr 2019

Bibliographical note

Short Title: pCLE diagnosis of Barrett’s-associated low-grade dysplasia


  • Barrett’s esophagus
  • esophageal adenocarcinoma
  • endoscopic imaging
  • confocal laser endomicroscopy


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