Sodium fluorescein–guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study

Schebesch, Karl‐Michael; Proescholdt, Martin; Höhne, Julius; Hohenberger, Christoph; Hansen, Ernil; Riemenschneider, Markus J.; Ullrich, W.; Doenitz, Christian; Schlaier, J.; Lange, Max; Brawanski, Alexander

doi:10.1007/s00701-013-1643-y

Cited by 167 publications

(110 citation statements)

References 28 publications

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“…This might be related also to the use of specific filters that enable reduction of the total dose of fluorescein injected 1,8,18 with a possible impact on reduction of side effects. Rare adverse events, including anaphylactic reactions, after fluorescein injection have been reported in the ophthalmological and neurosurgical literature, 3,9,10,16,28,33 but no side effects were registered with the use of low-dose fluorescein in more recent pa- pers.…”

Section: Discussionmentioning

confidence: 99%

“…14 In addition, the feasibility of fluorescein-guided removal of HGGs has been suggested by the results of several studies. 8,18,20 The results of one prospective study suggested a possible improvement of the extent of resection using fluorescein, although in that study surgery was performed without a specific filter integrated into the surgical microscope. 5 In 2011, our group started the first prospective Phase-II trial with the aid of a microscope-integrated fluorescence kit (FLUOGLIO) to evaluate the safety of and obtain initial data about the efficacy of fluorescence-guided resection of HGGs.…”

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confidence: 99%

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Is fluorescein-guided technique able to help in resection of high-grade gliomas?

Acerbi¹,

Broggi²,

Eoli

et al. 2014

FOC

146

114

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Object Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. Methods The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45–74 years), enrolled in the study since September 2011. In all cases fluorescein (5–10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. Results The median preoperative tumor volume was 30.3 cm3 (range 2.4–87.8 cm3). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. Conclusions Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

Acerbi¹,

Broggi²,

Eoli

et al. 2014

FOC

146

114

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“…The emergence of surgical microscopes outfitted with a fluorescein-specific filter has enabled broader application of fluorescein guidance to glioma microsurgery 2,17,26 with a statistically strong association between fluorescein staining and tumor tissue, as well as reports that fluorescein guidance safely facilitates complete resection of contrast-enhancing (CE) tumor. 1,9 However, small study groups have offered limited evidence of the added utility of fluorescein guidance, and rigorous assessment of fluorescein as a marker for tumor pathology in regions beyond MRI contrast enhancement has not been performed.…”

Section: 27mentioning

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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“…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. 10 However, conjugation of fluorescein to albumin demarcates glioblastoma tumors in humans and animal models.…”

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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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Sodium fluorescein–guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study

Cited by 167 publications

References 28 publications

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

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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