Detection of cholangiocarcinoma in vivo using miniprobe-based confocal fluorescence microscopy

Background: The preoperative diagnosis of cholangiocarcinomas is associated with low accuracy. Here a new imaging modality was evaluated to detect neoplasia in vivo in the biliary tract.

Methods: Mucosal imaging was performed with a confocal laser scanning miniprobe after intravenous injection of fluorescein 1%. After an initial feasabilty study performed in two pigs, a total of 14 patients with biliary strictures were examined in vivo with a specially designed miniaturized confocal laser probe thin enough to be inserted through the accessory channel of a peroral cholangioscope. In the first half, the probe was inserted directly into the common bile duct, whereas the cholangioscopical approach was used in the latter seven patients.

Results: Miniprobes could be inserted into the common bile duct without problems. However, stenosis could not be reached with confocal miniprobes in two of seven patients of the first series in whom imaging was conducted directly. These patients were therefore excluded from further analysis. Hence, adequate laser microscopic video sequences could be stored and biopsies could be taken of the remaining 12 patients including all 7 patients with the probe targeted under direct visual control. Presence of irregular vessels was the laser microscopic hallmark able to predict neoplasia with a sensitivity, specificity and overall diagnostic accuracy of 5/6 (83.3%), 6/6 (100%) and 11/12 (91.7%). Confocal microscopy was thereby superior to histopathology of biopsy specimens taken from strictures (accuracy: 76.9%). Mean signal-to-noise-ratio of laser microscopic images acquired from malignant strictures differed significantly from that of benign stenosis (p=0.003).

Conclusion: The methodology described represents a promising and reproducible diagnostic imaging approach for the detection of cancers even in small ducts such as the biliary system. This new tool could be of upmost importance as cholangiocarcinoma remains one of the cancers with the poorest prognosis.

Keywords: endomicroscopy, cancer detection, biliary tract, optical fiber, confocal