title: Aggressive resection at the infiltrative margins of glioblastoma facilitated by intraoperative fluorescein guidance.
abstract: 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.
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Neira
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Ung
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Sims
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Hani R
authors.initials: HR
authors.lastname: Malone
authors.affiliation: Neuroradiology.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Chow
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Samanamud
authors.affiliation: Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
authors.forename: George J
authors.initials: GJ
authors.lastname: Zanazzi
authors.affiliation: Radiology, and.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Guo
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Bowden
authors.affiliation: Radiology, and.
authors.forename: Binsheng
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Sheth
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sisti
authors.affiliation: Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Randy S
authors.initials: RS
authors.lastname: D'Amico
authors.affiliation: Departments of 1 Neurological Surgery.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D019793:Fluorescein / Q000008:administration & dosage; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D019635:Neurosurgical Procedures / Q000379:methods; D025321:Surgery, Computer-Assisted; D055815:Young Adult
chemical_list: D003287:Contrast Media; D019793:Fluorescein
keywords: 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; 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; fluorescein; fluorescence-guidance; fluorescence-guided resection; glioblastoma; high-grade glioma; n-ANOVA = multiway ANOVA; oncology