Development and Validation of Confocal Endomicroscopy Diagnostic Criteria for Low-Grade Dysplasia in Barrett's Esophagus

Abstract

OBJECTIVES: 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 2 prospective studies. In phase I, 2 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 = 57). The area under receiver operating characteristic curve was constructed to find the best cutoff. Sensitivity, specificity, interobserver, and intraobserver agreements were calculated. RESULTS: In phase I, 6 out of 8 criteria achieved the agreement and accuracy thresholds (i) dark nonround glands, (ii) irregular gland shape, (iii) lack of goblet cells, (iv) sharp cutoff of darkness, (v) variable cell size, and (vi) cellular stratification. The best cutoff for LGD diagnosis was 3 out of 6 positive criteria. In phase II, the diagnostic criteria had a sensitivity and specificity for LGD of 81.9% and 74.6%, respectively, with an area under receiver operating characteristic of 0.888. The interobserver agreement was substantial (κ = 0.654), 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 a substantial interobserver agreement.

Image-Enhanced Endoscopy and Molecular Biomarkers Vs Seattle Protocol to Diagnose Dysplasia in Barrett’s Esophagus

“…1 BE has an estimated risk of progression to cancer of 0.3% per year, which increases 10-to 50-fold when low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are diagnosed. [2][3][4] Treatment of dysplastic BE with endoscopic ablation prevents progression to cancer, 4,5 therefore endoscopic surveillance of BE is recommended. 6,7 Because dysplasia can be invisible on high-resolution white-light endoscopy (HRWLE), nontargeted biopsies are recommended according to the Seattle protocol.…”

Confocal laser endomicroscopy in the diagnostics of esophageal diseases: a pilot study

“…However, this work did not evaluate the ability of these criteria to diagnose LGD. Diagnostic criteria from di Pietro et al (9) in 2019 have recently been published. The best cutoff for LGD diagnosis was the positivity of any 3 of the 6 following criteria: dark non -round glands, irregular gland shape, lack of goblet cells, sharp cutoff of darkness, variable cell size, and cellular stratification.…”

“…A review of the current literature about pCLE in esophageal diseases was carried out first. Then the pCLE images from previously published articles, classifications and criteria for pCLE were studied (Miami classification for BE published by Wallace, with the addition of the description for low -grade dysplasia (LGD) by di Pietro and for high -grade dysplasia (HGD) by Gaddam (7)(8)(9).…”

Confocal laser endomicroscopy in gastro-intestinal endoscopy: technical aspects and clinical applications

“…By including only highquality videos, accuracy and agreement rose to 95% and κ=0.89, respectively. Recently, pCLE criteria for LGD have been developed (14). The CLE features of LGD are similar to those of more advanced dysplasia however reflect the more subtle histological abnormalities.…”