Fluorescence-guided surgery of metastatic brain tumors using fluorescein sodium

Okuda, Takeshi; Kataoka, Keisuke; Yabuuchi, Tomonari; Yugami, Haruki; Kato, Aitaro

doi:10.1016/j.jocn.2009.06.033

Cited by 84 publications

(51 citation statements)

References 21 publications

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“…Their findings are in accordance with a prior study conducted by Okuda and colleagues [1], though Okuda and colleagues used fluorescein sodium under white light without a particular microscope filter.…”

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confidence: 90%

Does fluorescein sodium-guided resection of cerebral metastases increase rates of total resections?

Gempt

2015

Acta Neurochir

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In their article BFluorescein sodium-guided resection of cerebral metastases-experience with the first 30 patients^, Schebesch and colleagues examine the use of fluorescein sodium dye in patients harboring brain metastases. In their retrospective patient series, 30 patients with different tumor entities were included. All patients underwent surgical resection of brain metastasis while using fluorescein sodium and a YELLOW 560 nm (ZEISS) filter. According to them, sufficient fluorescent staining was observed in 27 patients and complete tumor resection in 25 patients.Their findings are in accordance with a prior study conducted by Okuda and colleagues [1], though Okuda and colleagues used fluorescein sodium under white light without a particular microscope filter.While of course their retrospective study permits no conclusion that the use of fluorescein sodium will help to improve the neurosurgical treatment of patients with brain metastases in regard to the extent of resection and local control rate, we consider their study an important step in the right direction.Cerebral metastases are a very common problem and many more patients suffer from brain metastases than intrinsic brain tumors. Due to significant improvements in cancer therapies and imaging techniques, more and more patients are eligible for a neurosurgical treatment.Therefore it is the neurosurgeon's challenge to improve the surgical treatment of these patients as well. As long as local control rates are comparably low and the extent of resection in patients with brain metastases is well below the desirable 100 %, new techniques should be introduced, and of course tested for their validity, particularly since the use of fluorescent staining in neurosurgery is well established for highgrade gliomas for almost 10 years now [2].So far we only know that most metastases shine yellow. This is good, but only the first step. A properly designed trial seems necessary, in which rate of resection and the role of supramarginal resection is addressed.

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confidence: 90%

Does fluorescein sodium-guided resection of cerebral metastases increase rates of total resections?

Gempt

2015

Acta Neurochir

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“…Fluorescein sodium, an easily administered, widely marketed, biosafe green-fluorescing dye, has been used as an adjunct for the resection of intracranial tumors since the 1940s, 20,21 as well as in numerous other medical applications. 22 The extravasation of fluorescein 9 via disruptions in the blood-brain barrier (BBB) leads to accumulation in the extracellular space and high fluorescence. 9,29 In comparison, dye leakage is minimal in tissue with an intact BBB and readily cleared from brain tissue.…”

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confidence: 99%

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

Neira

Ung

Sims

et al. 2017

Journal of Neurosurgery

126

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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

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“…25 This dye can be safely administered intravenously in humans and has been used clinically in multiple applications. 20 The use of fluorescein as a tumor marker for resection has been widely investigated for multiple tumor types, including skull base tumors, 6 metastatic brain tumors, 21 and high-grade gliomas. 10,11,16,23,24 Fluorescein has not been previously demonstrated as an agent that bioaccumulates in a glioblastoma flank xenograft model.…”

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confidence: 99%

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

Diaz

Dios

Hattab

et al. 2015

JNS

165

148

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abbreviatioNs BBB = blood-brain barrier; GTR = gross-total resection; IQR = interquartile range; NHA = normal human astrocyte; PBS = phosphate-buffered saline; PDGF = platelet-derived growth factor; PDGFB = PDGF beta; PDGFR = PDGF receptor; PDGFRA = PDGFR alpha; RCAS = replication-competent avian sarcoma-leukosis; RFP = red fluorescent protein; tva = tumor virus A. 6 Department of Pathology and Laboratory Medicine, Indiana University; and 7 Goodman Campbell Brain and Spine, Department of Neurological Surgery, Indiana University, Indianapolis, Indiana obJect Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross-total resection (GTR) using high doses of fluorescein sodium under white light. The recent introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore. However, the ability of fluorescein to specifically stain glioma cells is not yet well understood. methods The authors designed an in vitro model to assess fluorescein uptake in normal human astrocytes and U251 malignant glioma cells. An in vivo experiment was also subsequently designed to study fluorescein uptake by intracranial U87 malignant glioma xenografts in male nonobese diabetic/severe combined immunodeficient mice. A genetically induced mouse glioma model was used to adjust for the possible confounding effect of an inflammatory response in the xenograft model. To assess the intraoperative application of this technology, the authors prospectively enrolled 12 patients who underwent fluorescein-guided resection of their high-grade gliomas using low-dose intravenous fluorescein and a microscope-integrated fluorescence module. Intraoperative fluorescent and nonfluorescent specimens at the tumor margins were randomly analyzed for histopathological correlation. results The in vitro and in vivo models suggest that fluorescein demarcation of glioma-invaded brain is the result of distribution of fluorescein into the extracellular space, most likely as a result of an abnormal blood-brain barrier. Glioblastoma tumor cell-specific uptake of fluorescein was not observed, and tumor cells appeared to mostly exclude fluorescein. For the 12 patients who underwent resection of their high-grade gliomas, the histopathological analysis of the resected specimens at the tumor margin confirmed the intraoperative fluorescent findings. Fluorescein fluorescence was highly specific (up to 90.9%) while its sensitivity was 82.2%. False negatives occurred due to lack of fluorescence in areas of diffuse, low-density cellular infiltration. Margins of contrast enhancement based on intraoperative MRI-guided StealthStation neuronavigation correlated well with fluorescent tumor margins. GTR of the contrast-enhancing area as guided by the fluorescent signal was achieved in 100% of cases based on postoperative MRI. coNclusioNs Fluorescein sodiu...

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Fluorescence-guided surgery of metastatic brain tumors using fluorescein sodium

Cited by 84 publications

References 21 publications

Does fluorescein sodium-guided resection of cerebral metastases increase rates of total resections?

Does fluorescein sodium-guided resection of cerebral metastases increase rates of total resections?

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

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance

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