Real-time increased detection of neoplastic tissue in Barrett's esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial

Abstract

Background Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett’s esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been extensively evaluated. Objective To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade dysplasia (HGD) and early carcinoma (EC) in BE. Design International, prospective, multicenter, randomized, controlled trial. Setting Five tertiary referral centers. Patients A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC. Interventions All patients were examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were recorded before biopsy samples were obtained. The order of HD-WLE and NBI was randomized and performed by 2 independent, blinded endoscopists. All suspicious lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These locations were examined by pCLE, and a presumptive diagnosis of benign or neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken from all locations and were reviewed by a central pathologist, blinded to endoscopic and pCLE data. Main Outcome Measurements Diagnostic characteristics of pCLE. Results The sensitivity and specificity for HD-WLE were 34.2% and 92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or pCLE (P = .002 and P < .001, respectively). The sensitivity and specificity for HD-WLE or NBI were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%, respectively, for HD-WLE, NBI, or pCLE (P = .01 and P = .02, respectively). Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NBI, respectively, resulting in detection of all HGD/EC patients, although not statistically significant. Limitations Academic centers with enriched population. Conclusions pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE. This may allow better informed decisions to be made for the management and subsequent treatment of BE patients.

Evaluation of microvascular density in Barrett's associated neoplasia

“…11,12,18 Currently, imaging is largely a subjectively based process. However, further development of image software may provide means to quantify in vivo imaging.…”

“…[3][4][5][6][7] Endoscopists are exploiting neovascularization in Barrett's esophagus to detect neoplasia using novel imaging modalities, such as narrow band imaging and confocal laser endomicroscopy. [8][9][10][11][12] One of the features that endoscopists look for is the vascular pattern under narrow band imaging or confocal laser endomicroscopy. [8][9][10][11][12] Irregular or increased vascularity is a feature that endoscopists are looking for with these imaging modalities to identify significant superficial neoplasia, including both high-grade dysplasia and esophageal adenocarcinoma.…”

“…[8][9][10][11][12] One of the features that endoscopists look for is the vascular pattern under narrow band imaging or confocal laser endomicroscopy. [8][9][10][11][12] Irregular or increased vascularity is a feature that endoscopists are looking for with these imaging modalities to identify significant superficial neoplasia, including both high-grade dysplasia and esophageal adenocarcinoma.…”

Endoscopic diagnosis and therapies for Barrett esophagus: a review

“…Several studies have shown high accuracy rates when compared with standard examinations, with a substantial interobserver agreement (56)(57)(58)(59)(60)(61)(62). An international multicenter trial demonstrated that CLE significantly improved sensitivity for the detection of HGD or cancer compared with HD-WLE with random and targeted biopsies alone (34.2 % vs. 68.3 %) with no decrease in specificity (87.8 %) (63). Classification systems for Barrett's and dysplasia been described for endomicroscopy (56,(64)(65)(66).…”

Laser endomicroscopy for the intraoperative diagnostic

“…In the esophagus, studies are concerned with the detection of precancerous lesions in patients with " Barrett's syndrome " , a chronic infl ammatory disease. A fi rst clinical study by Sharma et al [2] showed that additional use of pCLE signifi cantly improved the ability to detect neoplasia in Barrett's esophagus patients compared with high defi nition endoscopy alone.…”