Intraoperative confocal laser endomicroscopy for real-time in vivo tissue characterization during surgical procedures

Abstract

Introduction: Probe-based confocal laser endomicroscopy (pCLE) is an innovative technique providing real-time, in vivo optical biopsies. A previous ex vivo phase of the study (PERSEE) allowed identifying accurate pCLE criteria for the diagnosis of hepatic and peritoneal surgical specimens. This study aimed at evaluating the pCLE role for in vivo intra-abdominal tissue characterization during digestive cancer surgical procedures.

Methods: Between October 2014 and July 2015, consecutive patients diagnosed with digestive cancers and scheduled for a surgical resection or an exploratory laparoscopy were prospectively enrolled. Endomicroscopic images were acquired using a motorized Confocal Miniprobe™ with a bending distal tip providing easy access to abdominal organs. It was connected to an endomicroscopy system that allowed near-infrared illumination (at a wavelength of 785 nm) in conjunction with indocyanine green for contrast agent. A live audiovisual transmission was established between the surgeon and the pathologist for real-time interpretation of optical biopsies. Intraoperative pCLE performance for the diagnosis of suspicious nodules was assessed using corresponding surgical histopathology as reference standard.

Results: 21 consecutive patients were successfully enrolled. Live audiovisual transmission between the surgeon and the pathologist was successfully established in all cases. 62 pCLE sequences were acquired from different tissues [peritoneum (n = 27), liver (n = 21), lymph node (n = 4), diaphragm (n = 3), colon (n = 3), stomach (n = 2), and adrenal gland (n = 2)]. Malignant tissues were identified by fluorescently enhanced irregular cancerous tubes contrasting with dark glandular lumen and extracellular matrix. pCLE sensitivities and specificities were 67% and 100%, and 38% and 100% for peritoneal and hepatic carcinogenesis, respectively. One benign incident was reported during the trial with no patient consequence.

Conclusions: Real-time intraoperative pCLE with near-infrared illumination is feasible and safe, provides additional information in terms of tissue characterization, and, in combination with telepathology, allows interactive collaboration between the surgeon and the pathologist during surgical procedures. Trial registration clinicaltrials.gov Identifier: NCT02312167.

Keywords: Cancer evaluation; Diagnostic laparoscopy; Diagnostic performance; Fluorescent-guided surgery; Intraoperative collaboration; Probe-based confocal laser endomicroscopy; Telepathology.