In vivo endomicroscopy improves detection of Barrett's esophagus–related neoplasia: a multicenter international randomized controlled trial (with video)

Abstract

BACKGROUND Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the gastrointestinal tract mucosa. However, there are limited data on endoscope-based eCLE for imaging Barrett’s esophagus (BE). OBJECTIVE To compare high definition white light endoscopy alone (HDWLE) with random biopsy (RB) and HDWLE+eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. DESIGN Multicenter randomized controlled trial. SETTING Academic medical centers. PATIENTS Adult BE patients undergoing routine surveillance or referred for early neoplasia. INTERVENTIONS Patients were randomized to HDWLE+RB (Group 1) or HDWLE+eCLE+TB (Group 2). Real time diagnoses and management plans were recorded after HDWLE in both groups, and after eCLE in Group 2. Blinded expert pathologic diagnosis was the reference standard. MAIN OUTCOME MEASUREMENTS Diagnostic yield, performance characteristics, clinical impact. RESULTS 192 BE patients were studied. HDWLE+eCLE+TB led to a lower number of mucosal biopsies, higher diagnostic yield for neoplasia (34% vs. 7%, p<.0001) compared to HDWLE+RB but with comparable accuracy. HDWLE+eCLE+TB tripled the diagnostic yield for neoplasia (22% vs. 6%, p=.002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (p<.0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. LIMITATIONS Tertiary referral centers and expert endoscopists limiting generalizability. CONCLUSIONS Real time eCLE and targeted biopsy after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision-making by altering the diagnosis and guiding therapy.

Optimizing the diagnosis and therapy of Barrett’s esophagus

“…This technique also showed good performance for the diagnosis of BE associated neoplasia, with a sensitivity and specificity of 92.9% and 98.4% respectively (49). Moreover, additional studies have shown that the use of eCLE with targeted biopsies has a higher diagnostic yield for BE associated neoplasia compared to standard biopsy protocol, with reduction in the number of biopsies needed (50,51). Real-time microscopic visualization of the mucosa is also achieved with the use of endocytoscopy, however its use has been limited in the management of BE patients due to poor image quality (48).…”

Imaging the Leaky Gut

“…Recently, confocal laser endomicroscopes (CLE) have been developed that allow magnifications of 1000Â with 1-micron resolution, enabling visualization of cellular and subcellular structures in vivo in real time. [1][2][3][4] Through the use of vascular and molecular contrast agents, multiple structural and functional events can be directly observed, including angiogenesis and monoclonal antibody-antigen binding to epithelial targets. 5 In aggregate, these technologies have opened new fields of endomicroscopy and functional imaging of the GI tract at cellular and subcellular level.…”

“…Previously explored applications of these new CLE technologies include detection and classification of neoplasia in the colonic polyps, 6,7 inflammatory bowel disease, 8,9 Barrett's esophagus, 1 and the stomach. 10 Molecular imaging with tagged monoclonal antibody has enabled imaging of antiendothelial growth factor receptor monoclonal antibody binding to targets and predication of response to endothelial growth factor receptor chemotherapy.…”

“…A lthough overall cancer incidence slightly declined over the last decade, hepatocellular carcinoma (HCC) incidence rose in the United States. 1 Beyond established risk factors (alcohol, chronic viral hepatitis, tobacco, diabetes, obesity, aflatoxin exposure, and metabolic liver disease), accumulating evidence suggests an association between diet and HCC.…”

Confocal Laser Endomicroscopy and NSAID Enteropathy: Where Next?

“…To date, confocal endomicroscopy (CLE) has been used in cancer surveillance in inflammatory bowel disease and in Barrett's esophagus due to its ability to target endoscopic pinch biopsies to dysplastic mucosa [1,2]. Kiesslich et al reported that the use of CLE targeting increased the proportion of dysplasia-positive biopsies while decreasing the overall number of biopsies collected compared with conventional untargeted biopsy acquisition.…”