Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUO-GLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm 3 (range, 1.3-87.8 cm 3 ). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs.

Object Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. Methods The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45–74 years), enrolled in the study since September 2011. In all cases fluorescein (5–10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. Results The median preoperative tumor volume was 30.3 cm3 (range 2.4–87.8 cm3). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Conclusions Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Fluorescein is widely used as a fluorescent tracer for many applications. Its capacity to accumulate in cerebral areas where there has been blood-brain barrier damage makes it particularly suitable as a dye for the intraoperative visualization of malignant gliomas (MGs). In this report, we describe the results of a comprehensive review on the use of fluorescein in the surgical treatment of MGs. A comprehensive literature search and review for English-written articles concerning the use of fluorescein in the resection of MGs has been conducted. The search was executed through a PubMed literature search using the following keywords: malignant gliomas, glioblastomas, high-grade gliomas, YELLOW 560, total removal, dedicated filter, neurosurgery, brain tumors, intracranial tumors, and confocal microscopy. The literature search resulted in the retrieval of 412 evidence-based articles. Of these, 17 were found to be strictly related to the resection of MG with the aid of fluorescein. In addition to these 17, we have included 2 articles derived from a personal database of the corresponding author (FA). The analysis of the articles reviewed revealed three major applications of fluorescein during surgery for MGs that was documented: Fluorescein-guided resection of MGs with white-light illumination, fluorescein-guided resection of MGs with a surgical microscope equipped with a dedicated filter for fluorescein, and confocal microscopy for intraoperative histopathological analysis on MGs. The systemic review conducted on the use of fluorescein in MGs explored the applications and the different modalities in which fluorescein has been used. The data we have gathered indicates that fluorescein-guided surgery is a safe, effective, and convenient technique to achieve a high rate of total removal in MGs. Further prospective comparative trials, however, are still necessary to prove the impact of fluorescein-guided surgery on both progression-free survival and overall survival.

Objective: Sodium fluorescein, a green, water soluble dye, is used as neurosurgical fluorescent tracer thanks to its property to accumulate in cerebral regions of blood-brain barrier (BBB) disruption. The authors report the preliminary results of a prospective observational study regarding the use of fluorescein-guided technique for the resection of suspected malignant neoplasms of the central nervous system (CNS), contrast enhancing at preoperative magnetic resonance imaging (MRI), using a dedicated filter on the surgical microscope. Methods: In March 2016 the authors started a prospective, observational trial to evaluate intraoperative fluorescence's characteristics of CNS tumors, the percentage of extent of resection thanks to fluorescein aid and side effects related to fluorescein administration. This report is based on a preliminary analysis of the results of first 279 enrolled patients. Fluorescein was intravenously injected after intubation or immediately at the entrance in the operating room for awake procedures; the tumor was removed using a dedicated filter on the surgical microscope in an inside-out fashion until all fluorescent tissue was removed, as considered feasible by the surgeon. Results: The 279 patients finally enrolled in the trial, both firstly diagnosed and recurrent, were categorized according to WHO pathological classification and there were 212 neuroepithelial tumors, 25 brain metastases, 10 cerebral lymphomas, 7 hemangioblastomas, or hemangioendotheliomas and 25 other tumors and conditions. No adverse reaction related to the administration of fluorescein or to the combined use of fluorescein with other fluorophores was registered. Fluorescein accumulated in cerebral regions where the BBB was damaged, representing a significant surgical aid in most of the CNS tumors with contrast enhancement. In cases of complete removal of all fluorescent tissue, as intraoperatively judged by the surgeon, postoperative MRI revealed a gross total resection in 181/198 patients (91.4%). Conclusions: Based on these preliminary results, fluorescein-guided surgery with a dedicated filter on the microscope is a safe and effective technique to improve visualization and resection of different CNS tumors and conditions, based on BBB alteration.