Indocyanine green fluorescence in endoscopic transsphenoidal resection of pituitary neuroendocrine tumors: a systematic review

Background Over the last decade, endoscope integrated indocyanine green (E-ICG) fluorescence has been introduced in endoscopic skull base surgery. E-ICG seems to be a promising tool for intraoperative tissue differentiation, distinguishing pituitary neuroendocrine tumors (PitNET) from pituitary gland. More recent technical advancements have made E-ICG with simultaneous near-infrared/white-light overlay imaging available. E-ICG may improve intraoperative tumor identification, enabling more precise surgery and ultimately improved patient outcome. This systematic review evaluates the use of E-ICG for PitNET surgery. Methods A systematic review was performed in accordance with PRISMA guidelines. PubMed, EMBASE, MedLine and Scopus databases were searched using different terms for "pituitary adenoma" combined with "Indocyanine green". Data from relevant original papers were extracted and analyzed. Results Fifteen studies were included in the final analysis. The studies employed different ICG administration and fluorescence assessment protocols. Endpoints and methodology were heterogenous. Study populations varied from one to 39 cases. A total of 193 patients underwent transsphenoidal endoscopic surgery with E-ICG for PitNET. ICG dosage varied from 5 mg to 25 mg/kg. Thirteen studies administered ICG intraoperatively. Eleven studies utilized first-generation endoscopes, requiring toggling between near infrared light fluorescence and white light. Second generation dual or overlay mode endoscopes were used in four studies. Tumor fluorescence was assessed in eleven studies (141 cases). Six studies utilized a quantitative method to assess ICG-fluorescence. Seven studies specifically reported surgical complications. No safety issues regarding ICG use were reported. Conclusions The current literature is mainly based on small single center cohorts and case-studies, presenting a wide variety of approaches. Procedures and intraoperative assessment of fluorescence were mainly performed utilizing first-generation ICG endoscopes. There is lack of consensus in terms of ICG as an intraoperative tumor marker. Endoscopic ICG seems a promising tool for intraoperative real-time tissue differentiation, including vascular structures, tumor and pituitary gland.