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Diffuse low-grade gliomas are infiltrative tumors whose margins are not distinguishable from the adjacent healthy brain parenchyma. The aim was to precisely examine the results provided by the intraoperative use of macroscopic fluorescence in diffuse low-grade gliomas and to describe the new fluorescence-based techniques capable of guiding the resection of low-grade gliomas. Only about 20% and 50% of low-grade gliomas are macroscopically fluorescent after 5-amino-levulinic acid (5-ALA) or fluorescein sodium intake, respectively. However, 5-ALA is helpful for detecting anaplastic foci, and thus choosing the best biopsy targets in diffuse gliomas. Spectroscopic detection of 5-ALA-induced fluorescence can detect very low and non-macroscopically visible concentrations of protoporphyrin IX, a 5-ALA metabolite, and, consequently, has excellent performances for the detection of low-grade gliomas. Moreover, these tumors have a specific spectroscopic signature with two fluorescence emission peaks, which is useful for distinguishing them not only from healthy brain but also from high-grade gliomas. Confocal laser endomicroscopy can generate intraoperative optic biopsies, but its sensitivity remains limited. In the future, the coupled measurement of autofluorescence and induced fluorescence, and the introduction of fluorescence detection technologies providing a wider field of view could result in the development of operator-friendly tools implementable in the operative routine. Full article

The utilization of fluorescein-guided biopsies has recently been discussed to improve and expedite operative techniques in the detection of tumor-positive tissue, as well as to avoid making sampling errors. In this study, we aimed to report our experience with fluorescein-guided biopsies and elucidate distribution patterns in different histopathological diagnoses in order to develop strategies to increase the efficiency and accuracy of this technique. We report on 45 fluorescence-guided stereotactic biopsies in 44 patients (15 female, 29 male) at our institution from March 2016 to March 2021, including 25 frame-based stereotactic biopsies and 20 frameless image-guided biopsies using VarioGuide^®. A total number of 347 biopsy samples with a median of 8 samples (range: 4–18) per patient were evaluated for intraoperative fluorescein uptake and correlated to definitive histopathology. The median age at surgery was 63 years (range: 18–87). Of the acquired specimens, 63% were fluorescein positive. Final histopathology included glioblastoma (n = 16), B-cell non-Hodgkin lymphoma (n = 10), astrocytoma, IDH-mutant WHO grade III (n = 6), astrocytoma, IDH-mutant WHO grade II (n = 1), oligodendroglioma, IDH-mutant and 1p/19q-codeleted WHO grade II (n = 2), reactive CNS tissue/inflammation (n = 4), post-transplantation lymphoproliferative disorder (PTLD; n = 2), ependymoma (n = 1), infection (toxoplasmosis; n = 1), multiple sclerosis (n = 1), and metastasis (n = 1). The sensitivity for high-grade gliomas was 85%, and the specificity was 70%. For contrast-enhancing lesions, the specificity of fluorescein was 84%. The number needed to sample for contrast-enhancing lesions was three, and the overall number needed to sample for final histopathological diagnosis was five. Interestingly, in the astrocytoma, IDH-mutant WHO grade III group, 22/46 (48%) demonstrated fluorescein uptake despite no evidence for gadolinium uptake, and 73% of these were tumor-positive. In our patient series, fluorescein-guided stereotactic biopsy increases the likelihood of definitive neuropathological diagnosis, and the number needed to sample can be reduced by 50% in contrast-enhancing lesions. Full article

(1) Background: Gangliogliomas comprise a small number of brain tumors. They usually present as World Health Organization (WHO) grade I, and they delineate on gadolinium-enhanced MRI; the surgical goal is wide radical resection, and the course thereafter is usually benign. Fluorescein sodium (FL) tends to accumulate in areas with altered blood–brain barrier (BBB). Thus far, the results provided by prospective and retrospective studies show that the utilization of this fluorophore may be associated with better visualization and improvement of resection for several tumors of the central nervous system. In this study, we retrospectively studied the effect of fluorescein sodium on visualization and resection of gangliogliomas. (2) Methods: Surgical databases in three neurosurgical departments (Regensburg University Hospital; Besta Institute, Milano, Italy; and Liv Hospital, Istanbul, Turkey), with approval by the local ethics committee, were retrospectively reviewed to find gangliogliomas surgically removed by a fluorescein-guided technique by the aid of a dedicated filter on the surgical microscope from April 2014 to February 2020. Eighteen patients (13 women, 5 men; mean age 22.9 years, range 3 to 78 years) underwent surgical treatment for gangliogliomas during 19 operations. Fluorescein was intravenously injected (5 mg/kg) after general anesthesia induction. Tumors were removed using a microsurgical technique with the YELLOW 560 Filter (YE560) (KINEVO/PENTERO 900, Carl Zeiss Meditec, Oberkochen, Germany). (3) Results: No side effects related to fluorescein occurred. In all tumors, contrast enhancement on preoperative MRI correlated with bright yellow fluorescence during the surgical procedure (17 gangliogliomas WHO grade I, 1 ganglioglioma WHO grade II). Fluorescein was considered helpful by the operating surgeon in distinguishing tumors from viable tissue in all cases (100%). Biopsy was intended in two operations, and subtotal resection was intended in one operation. In all other operations considered preoperatively eligible, gross total resection (GTR) was achieved in 12 out of 16 (75%) instances. (4) Conclusions: The use of FL and YE560 is a readily available method for safe fluorescence-guided tumor resection, possibly visualizing tumor margins intraoperatively similar to contrast enhancement in T1-weighted MRI. Our data suggested a positive effect of fluorescein-guided surgery on intraoperative visualization and extent of resection during resection of gangliogliomas. Full article