Fluorescein sodium-guided surgery of malignant brain tumors: history, current concepts, and future projects

illumination methods.Furthermore, the introduction of imageguidance (neuro-navigation and intraoperative ultrasonography) facilitated the identification of tumor margins in the 1990s, thus improving the quality of resection of malignant brain tumors.Since the results of a phase-III trial confirmed a significantly higher rate of gross-total resection (GTR) with 5-ALA in comparison to resection under white light (48), fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) in combination with a dedicated surgical microscope filter (BLUE400, Carl Zeiss Meditec, Germany) has extended the neurosurgical armamentarium for HGG.However, the use of 5-ALA has also several distinct disadvantages.5-ALA is expensive, and its use must still be approved by the American Food and Drug Administration (FDA).Furthermore, exposure to light after 5-ALA injection may cause severe porphyria and other skin reactions that require complex patient management.The most important disadvantage for neurosurgeons, however, is that the use of █ INTRODUCTIONMalignant brain tumors such as high-grade gliomas (HGG) or cerebral metastases are devastating diseases.Modern comprehensive treatment of HGG consists of resection, chemotherapy, and radiation.The extent of resection (EOR) has been repeatedly proven to be one of the most important predictors of overall survival (OS), progression-free survival (PFS), and neurological outcome (21,25,31,43).Thus, consensus exists that -whenever safely possible-neurosurgical resection should aim at completely removing contrast-enhanced tissue in the preoperative T1-weighted magnetic resonance (MR) sequence.Accordingly, the EOR is known to significantly increase the efficacy of any adjuvant treatment of both recurrent HGG and cerebral metastases by prolonging OS and PFS and improving neurological outcome (20,39,53).Since the invention of the surgical microscope in the 1960s, both the accuracy and efficacy of neurosurgical performance has been steadily increased by improved magnification and Fluorescein sodium (FL)-guided resection has become an important and beneficial treatment method for malignant brain tumors.FL-guided resection improves the rate of gross total resection in high-grade gliomas (HGG) and cerebral metastases (CM).FL sensitively visualizes the disruption of the blood-brain barrier in the area surrounding malignant lesions, similar to contrast-enhanced T1-weighted MR sequences.This review of the current literature summarizes the history of FL in neurosurgery from 1946 until today.We discuss the molecular mechanism of FL accumulation in cerebral malignant tumors and provide an overview of the current practice of using FL and applying a dedicated surgical microscope filter.Additionally, we outline and discuss ongoing trials and future projects.