Combined Fluorescence Using 5-Aminolevulinic Acid and Fluorescein Sodium at Glioblastoma Border: Intraoperative Findings and Histopathologic Data About 3 Newly Diagnosed Consecutive Cases.

Abstract

Fluorescence-guided glioblastoma surgery is an intraoperative technique developed in recent years. Two main compounds have been used so far: 5-amilovelulinic acid (5-ALA) and fluorescein sodium (Fl-Na). Despite a large amount of literature on both techniques, few data are available on the use of both compounds in the same patient. Three consecutive patients affected by a newly diagnosed glioblastoma underwent surgical resection using both 5-ALA and Fl-Na. 5-ALA was orally administered 3 hours before induction of anesthesia at a dosage of 20 mg/kg, whereas fluorescein was intravenously administered at induction of anesthesia at a dosage of 4 mg/kg. Tumor resection was carried out combining these fluorophores. At tumor borders, multiple samples were collected, and fluorescent pattern of each sample was registered. Samples were then analyzed by a neuropathologist blinded for intraoperative fluorescence findings. Eighteen samples were analyzed. At tumor margin, bright pink fluorescence was highly indicative of residual tumor (positive predictive value [PPV], 94%), and it was superior to faint pink and fluorescein (PPVs, 89% and 87%, respectively). The gradual reduction of pink fluorescence warned of the risk of gradually entering healthy tissue (specificity of 67% compared with 33% with fluorescein). Using 5-ALA, detecting no fluorescence was highly suggestive of healthy tissue (negative predictive value of 100% compared with 50% with fluorescence). In our experience with 3 patients, the 2 techniques presented different advantages and limitations in specific steps of tumor resection, showing complementary properties. Larger studies are mandatory to investigate the synergistic use of both techniques.