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Autofluorescence-Directed Confocal Endomicroscopy in Combination With a Three-Biomarker Panel Can Inform Management Decisions in Barrett's Esophagus.


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Authors

di Pietro, Massimiliano 
Bird-Lieberman, Elizabeth L 
Liu, Xinxue 
Nuckcheddy-Grant, Tara 
Bertani, Helga 

Abstract

OBJECTIVES: Barrett's esophagus (BE) surveillance with white-light endoscopy and quadrantic biopsies (Seattle protocol) is resource intensive and limited by sampling error. Previous work suggests that autofluorescence imaging (AFI) in combination with a molecular panel might reduce the number of biopsies, but this was not sufficiently sensitive for low-grade dysplasia, now a point for endoscopic intervention. Here we used AFI to direct narrow-field imaging tools for real-time optical assessment of dysplasia and biopsies for a biomarker panel. We compared the new diagnostic algorithm with the current standard. METHODS: A total of 55 patients with BE were recruited at a single tertiary referral center. Patients underwent high-resolution endoscopy followed by AFI. AFI-targeted areas (n=194) were examined in turn by narrow-band imaging with magnification (NBIz) and probe-based confocal laser endomicroscopy (pCLE). Biopsies were taken from AFI-targeted areas and tested using an established molecular panel comprising aneuploidy plus cyclin A and p53 immunohistochemistry. RESULTS: In the per-patient analysis the overall sensitivity and specificity of AFI-targeted pCLE were 100% and 53.6% for high-grade dysplasia/intramucosal cancer and 96.4% and 74.1% for any grade of dysplasia, respectively. NBIz had equal specificity for dysplasia detection (74.1%), but significantly lower sensitivity (57.1%) than pCLE. The time required to perform AFI-targeted pCLE was shorter that that taken by the Seattle protocol (P=0.0004). We found enrichment of molecular abnormalities in areas with optical dysplasia by pCLE (P<0.001), regardless of histologic dysplasia. The addition of the 3-biomarker panel reduced the false positive rate of pCLE by 50%, leading to sensitivity and specificity for any grade of dysplasia of 89.2% and 88.9%, respectively. CONCLUSIONS: The combination of pCLE on AFI-targeted areas and a 3-biomarker panel identifies patients with dysplasia.

Description

Keywords

Aged, Algorithms, Aneuploidy, Barrett Esophagus, Biomarkers, Biopsy, Cyclin A, Disease Progression, Esophagoscopy, Esophagus, False Positive Reactions, Female, Humans, Male, Microscopy, Confocal, Middle Aged, Narrow Band Imaging, Optical Imaging, Precancerous Conditions, Sensitivity and Specificity, Tumor Suppressor Protein p53, Watchful Waiting

Journal Title

Am J Gastroenterol

Conference Name

Journal ISSN

0002-9270
1572-0241

Volume Title

110

Publisher

Ovid Technologies (Wolters Kluwer Health)
Sponsorship
TCC (None)
Medical Research Council (MC_UU_12022/2)
This study was funded by an Addenbrookes Charitable Trust grant to M.d.P. and Medical Research Council Program Grant to R.C.F., with additional clinical research infrastructure support from the Experimental Cancer Medicine Centre and the Cambridge Biomedical Research Centre. This was an NIHR portfolio study (UKCRN ID 7561).