Feasibility of laser marking in Barrett's esophagus with volumetric laser endomicroscopy: first-in-man pilot study

Background and Aim: Volumetric laser endomicroscopy (VLE) provides a circumferential scan of the esophageal wall layers and has potential to improve detection of neoplasia in Barrett's esophagus (BE). The novel VLE laser marking system enables direct in vivo marking of suspicious areas as identified on VLE. These laser marked areas can subsequently be targeted for biopsies. The aim was to evaluate the visibility and positional accuracy of laser marks (LMs) in different esophageal tissue types on white light endoscopy (WLE) and VLE. Methods: Patients with BE with or without neoplasia underwent imaging with VLE. Protocol refinements were practiced in a learning phase. In the second phase, visibility of LMs was assessed by random marking in squamous, BE, and gastric tissue. In phase 3, positional accuracy of the LMs was tested by identifying and laser marking surrogate targets (endoscopically placed cautery marks). In the final phase, the most suspicious areas for neoplasia were identified in each patient using VLE, targeted by LMs, and biopsy samples subsequently obtained. Results: Sixteen patients with BE were included (14men; median age, 68 years), 1 of whom was included twice in different study phases. Worst histologic diagnoses were 9 non-dysplastic Barrett's esophagus (NDBE), 3 low-grade dysplasia (LGD), 4 high-grade dysplasia (HGD), and 1 early adenocarcinoma (EAC). In total, 222 LMs were placed, of which 97% was visible on WLE. All LMs were visible on VLE directly after marking, and 86% could be confirmed during post hoc analysis. LM targeting was successful with positional accuracy in 85% of cautery marks. Inaccurate targeting was caused by system errors or difficult cautery mark visualization on VLE. In the final phase (5 patients), 18 areas suspicious on VLE were identified, which were all successfully targeted by LMs (3 EAC, 3 HGD, 1 LGD, and 11 NDBE). Mean VLE procedure time was 22 minutes (+/- 6 minutes standard deviation); mean endoscopy time was 56 minutes (+/- 17 minutes). No adverse events were reported. Conclusions: This first-in-human study of VLE-guided laser marking was found to be feasible and safe in 17 procedures. Most LMs were visible on WLE and VLE. Targeting VLE areas of interest proved to be highly successful. VLE-guided laser marking may improve the detection and delineation of Barrett's neoplasia in the future