Indocyanine Green Fluorescence for the Intraoperative Detection of Extrahepatic Hepatocellular Carcinoma: a Systematic Review and Pooled-Analysis

Indocyanine green (ICG) is exclusively uptaken by hepatocytes and rapidly cleared. Hepatocellular carcinoma (HCC) cells may also uptake ICG, but their clearance may be impaired, thus remaining fluorescent for a prolonged period of time. This characteristic may be exploited to visualize not only intrahepatic HCCs, but also extrahepatic HCC implants. We conducted a systematic literature search on Medline, Scopus, Web of Science (WoS) Core Collection and the Cochrane library to identify studies on the use of ICG fluorescence for the intraoperative visualization of extrahepatic HCC until December 2024. Eleven studies were included for a total of 44 patients: seven studies were case reports, two studies were small case series (2 patients), and two studies were larger case series (≥ 15 patients). The studies reported a total of 119 lesions suspected of extrahepatic localization of HCC with an ICG-detection rate after intravenous ICG infusion of 89.0%; 22 new lesions positive for ICG fluorescence not suspected during pre-operatory planning were identified intraoperatively. Among all removed fluorescent lesions, only 4 were negative for HCC. Sensitivity was 91.9%, specificity 33.3% (based on only 6 HCC-negative lesions), accuracy 89.4% while the positive predictive value 96.9%. Per-site diagnostic accuracy varied substantially, as sensitivity was 89.2% for the lungs, 93.8% for lymph nodes and 100% for peritoneum. Overall, the use of ICG as a guiding tool for intraoperative identification and dissection of extrahepatic localization of HCC appears promising, although further evidence is needed to assess whether ICG can become a standard of care in this setting. • ICG fluorescence enables intraoperative detection of extrahepatic HCC • Pooled-analysis including 44 patients and 119 suspected lesions • ICG allows intraoperative detection of unsuspected lesions • High SE and PPV support intraoperative surgical guidance • Limited specificity warrants multimodal intraoperative assessment