Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance

Abstract

ABBREVIATIONS 5-ALA = 5-aminolevulinic acid; BBB = blood-brain barrier; CE = contrast enhancing; CUMC = Columbia University Medical Center; EOR = extent of resection; GBM = glioblastoma; GTR = gross-total resection; HGG = high-grade glioma; n-ANOVA = multiway ANOVA; NCE = non-contrast enhancing; OS = overall survival; PFS = progression-free survival; PPV = positive predictive value; ROI = region of interest; STR = subtotal resection; UD = undetermined; WHO = World Health Organization; Y560 = YELLOW 560. OBJECTIVE Extent of resection is an important prognostic factor in patients undergoing surgery for glioblastoma (GBM). Recent evidence suggests that intravenously administered fluorescein sodium associates with tumor tissue, facilitating safe maximal resection of GBM. In this study, the authors evaluate the safety and utility of intraoperative fluorescein guidance for the prediction of histopathological alteration both in the contrast-enhancing (CE) regions, where this relationship has been established, and into the non-CE (NCE), diffusely infiltrated margins. METHODS Thirty-two patients received fluorescein sodium (3 mg/kg) intravenously prior to resection. Fluorescence was intraoperatively visualized using a Zeiss Pentero surgical microscope equipped with a YELLOW 560 filter. Stereotactically localized biopsy specimens were acquired from CE and NCE regions based on preoperative MRI in conjunction with neuronavigation. The fluorescence intensity of these specimens was subjectively classified in real time with subsequent quantitative image analysis, histopathological evaluation of localized biopsy specimens, and radiological volumetric assessment of the extent of resection. RESULTS Bright fluorescence was observed in all GBMs and localized to the CE regions and portions of the NCE margins of the tumors, thus serving as a visual guide during resection. Gross-total resection (GTR) was achieved in 84% of the patients with an average resected volume of 95%, and this rate was higher among patients for whom GTR was the surgical goal (GTR achieved in 93.1% of patients, average resected volume of 99.7%). Intraoperative fluorescein staining correlated with histopathological alteration in both CE and NCE regions, with positive predictive values by subjective fluorescence evaluation greater than 96% in NCE regions. CONCLUSIONS Intraoperative administration of fluorescein provides an easily visualized marker for glioma pathology in both CE and NCE regions of GBM. These findings support the use of fluorescein as a microsurgical adjunct for guiding GBM resection to facilitate safe maximal removal. SUBMITTEDhttps://thejns.org/doi/abs/10.3171/2016.7.JNS16232

Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO)

“…These data are similar to that obtained by Murray and colleagues, who systematically studied SF accuracy in tumor identification, performing 186 biopsies in 23 patients with brain malignancies, and obtaining a sensitivity of 96% and a specificity of 81% (48). Furthermore, it has been recently demonstrated that intraoperative fluorescein staining correlated with histologic alteration both in contrast enhanced and in noncontrast enhanced regions, with a sensitivity of 75.6% and a specificity of 75% (41). We are aware that sensitivity, specificity, PPV, and NPV measured in our samples, and in other similar studies, are biased by the conditionality of surgical samples, especially in the peritumoral "healthy" tissue.…”

Probe-based three-dimensional confocal laser endomicroscopy of brain tumors: technical note

“…Since its introduction, fluorescence-guided tumor resection has been the subject of considerable scrutiny and investigation 5–10. Intravenously injected FNa accumulates in regions with a disrupted blood–brain barrier secondary to various causes, including the presence of tumor or intraoperative iatrogenic injury.…”

Fluorescein-Guided Surgery for Pediatric Brainstem Gliomas: Preliminary Study and Technical Notes

“…17 Most studies have demonstrated that the enhancement pattern of fluorescein was similar to the contrast enhancement on MRI. [18][19][20] The typical appearance of fluorescein is to turn the tumor yellowish-green, while the peripheral brain tissue remains in its natural color.…”

“…It has been noted that the enhancing pattern of fluorescein is similar to contrast enhancement due to the mechanism of penetrating the disrupted blood-brain barrier. 19,20 According to our inclusion criteria, every tumor was enhanced on pre-operative MRI. Thus, it is certain that all tumors were stained and illuminated under the microscope.…”