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Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus

Vithayathil, Mathew; Modolell, Ines; Ortiz-Fernandez-Sordo, Jacobo; Oukrif, Dahmane; Pappas, Apostolos; Januszewicz, Wladyslaw; O'Donovan, Maria; ... di Pietro, Massimiliano; + view all (2022) Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus. Clinical Gastroenterology and Hepatology 10.1016/j.cgh.2022.01.060. (In press). Green open access

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Abstract

BACKGROUND: Dysplasia in Barrett's esophagus (BE) is often invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers versus HRWLE with Seattle protocol biopsies. METHODS: BE patients with no dysplastic lesions were block randomized to standard endoscopy (HRWLE with Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6-12 weeks. Histological endpoint was diagnosis from all study biopsies (trial histology). Sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. Primary outcome was diagnostic accuracy for dysplasia by real-time pCLE versus HRWLE biopsies. RESULTS: Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared to standard endoscopy [74.3% (95%CI, 56.7-87.5) vs 80.0% (95%CI 63.1-91.6), p=0.48]. Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53 and aneuploidy had strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than Seattle protocol (81.5% vs 51.9%, p<0.001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; p=0.16) with an area under receiver operating curve of 0.83. CONCLUSIONS: Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. Addition of molecular biomarkers could improve diagnostic accuracy.

Type: Article
Title: Image enhanced endoscopy and molecular biomarkers vs Seattle protocol to diagnose dysplasia in Barrett's esophagus
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cgh.2022.01.060
Publisher version: https://doi.org/10.1016/j.cgh.2022.01.060
Language: English
Additional information: Copyright © 2022 by the AGA Institute. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Autofluorescence, Barrett’s esophagus, Confocal laser endomicroscopy, Dysplasia, Esophageal adenocarcinoma
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10144933
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