Probe-based confocal laser endomicroscopy intra-operative evaluation in ovarian cancer: definition of in vivo architectural patterns to determine resection strategies

Objective: Probe-based confocal laser endomicroscopy (pCLE) is a novel real-time imaging technique that is potentially useful for accurately distinguishing between normal and cancerous tissues. The aim of this study was to describe the pCLE patterns of areas suggestive of tumors and evaluate the ability of the method to differentiate between normal and cancerous tissue during cytoreductive surgery for epithelial ovarian cancer. Methods: In vivo pCLE images and subsequent biopsies were acquired from various anatomical sites including the parietal and visceral peritoneum, ovaries, and omentum. Each endomicroscopic sequence was analyzed by highly experienced investigators using pCLE imaging for cancer diagnosis. Each pCLE sequence was compared with the histology of the corresponding specimens. Results: We enrolled 18 women with International Federation of Gynecology and Obstetrics stage III/IV high-grade serous epithelial ovarian cancer referred for primary or interval debulking surgery. A total of 112 biopsies were obtained for histologic analysis. The pCLE images of normal tissue showed a regular distribution of stromal fibers and consistent cellular architecture, regardless of the anatomical region, with vascularized areas characterized by regular vessels. Conversely, the extravasation of fluorescein, used as a contrast agent, was a distinguishing feature of malignant nodules, which were easily recognized by leakage and are typical of tumor-associated vessels. The leakage often surrounded the dark clusters of neoplastic cells. A substantial agreement between pCLE and histology emerged (k = 0.66), whereas only a fair concordance between the surgeon's intra-operative assessment and histology was found (k = 0.30). Conclusions: Our results suggest that pCLE is a promising intra-operative technique to assist surgeons in accurately detecting peritoneal metastases in patients with advanced epithelial ovarian cancer, enhancing surgical radicality while avoiding unnecessary resection.