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.
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Authors | Massimiliano di Pietro, Elizabeth L Bird-Lieberman, Xinxue Liu, Tara Nuckcheddy-Grant, Helga Bertani, Maria O'Donovan, Rebecca C Fitzgerald |
Journal | The American journal of gastroenterology
(Am J Gastroenterol)
Vol. 110
Issue 11
Pg. 1549-58
(Nov 2015)
ISSN: 1572-0241 [Electronic] United States |
PMID | 26416188
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Biomarkers
- Cyclin A
- Tumor Suppressor Protein p53
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Topics |
- Aged
- Algorithms
- Aneuploidy
- Barrett Esophagus
(genetics, metabolism, pathology)
- Biomarkers
(analysis)
- Biopsy
- Cyclin A
(analysis)
- Disease Progression
- Esophagoscopy
- Esophagus
(pathology)
- False Positive Reactions
- Female
- Humans
- Male
- Microscopy, Confocal
(methods)
- Middle Aged
- Narrow Band Imaging
- Optical Imaging
- Precancerous Conditions
(chemistry, genetics, pathology)
- Sensitivity and Specificity
- Tumor Suppressor Protein p53
(analysis)
- Watchful Waiting
(methods)
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