Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps syste

Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on histological correlation

Volumetric laser endomicroscopy (VLE) is a novel balloon-based optical coherence tomography (OCT) imaging technique that may improve detection of early neoplasia in Barrett's esophagus (BE). Most OCT studies lack a direct correlation between histology and OCT images. The aim is to investigate the optimal approach for achieving one-to-one correlation of ex-vivo VLE images of endoscopic resection (ER) specimens with histology. BE patients with and without early neoplasia underwent ER after delineating areas with electrocoagulation markers (ECM). After ER, specimens underwent additional ex-vivo marking with several different markers (ink, pin, Gold Probe) followed by ex-vivo VLE scanning. ER specimens were carefully sectioned into tissue blocks guided by the markers. Histology and VLE slides were considered a match if ≥ 2 markers were visible on both modalities and mucosal patterns aside from these markers matched on both histology and VLE. From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained multiple markers. Fourteen histology-VLE matches were identified. ECMs and ink markers proved to be the most effective combination for matching. The last 6/16 ER specimens yielded 9/14 matches, demonstrating a learning curve due to methodological improvements in marker placement and tissue block sectioning. One-to-one correlation of VLE and histology is complex but feasible. The groundwork laid in this study will provide high-quality histology-VLE correlations that will allow further research on VLE features of early neoplasia in B

The Amsterdam ReBus progressor cohort: identification of 165 Barrett's surveillance patients who progressed to early neoplasia and 723 nonprogressor patients

Patient selection is suboptimal in most studies focused on identifying biological markers for neoplastic progression in Barrett's esophagus (BE). This study aims to describe a stringently selected community-based case-control cohort of non-dysplastic BE (NDBE) patients who progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and BE patients who never progressed to be used for future biomarker studies. We identified all patients referred for endoscopic work-up of BE neoplasia at three tertiary referral centers for treatment of BE neoplasia between 2000 and 2013. We performed a detailed registration of any endoscopic surveillance history before neoplastic progression. Controls were selected from a retrospective BE surveillance registration in 10 community hospitals. A total of 887 patients were referred for endoscopic work-up of BE neoplasia. Based on predefined selection criteria, we identified 165 progressor patients (82% men; mean age 55 years ± 10.4) with a baseline endoscopy demonstrating NDBE > 2 years before neoplastic progression. Using the same predefined selection criteria, 723 nonprogressor patients (67% men; mean age 57 years ± 11.3) with >2 years of endoscopic surveillance were identified. Median length of the BE segment was 5 cm (IQR 4-7) in progressors and 4 cm (IQR 2-6) in controls. Median duration of surveillance was 89 months (IQR 54-139) in progressors and 76 months (IQR 47-116) in nonprogressors. Paraffin embedded biopsies are available for biomarker research in all patients. Ethical approval was obtained and material transfer agreements were signed with all 58 contributing pathology labs. This is the largest community-based case-control cohort of BE patients with and without progression to early neoplasia. The stringent selection criteria and the availability of paraffin embedded biopsy specimens make this a unique cohort for biomarker studies