Gross Total Resection of Glioma with the Intraoperative Fluorescence-guidance of Fluorescein Sodium

Chen, Bin; Wang, Haifeng; Ge, Pengfei; Zhao, Jingwei; Li, Wenchen; Gu, Hui; Wang, Guangming; Luo, Yi-nan; Chen, Fan

doi:10.7150/ijms.4843

Cited by 110 publications

(102 citation statements)

References 23 publications

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“…Gross-total resection of glioma has been reported in 8 of 10 patients with the use of fluorescein administered at a dose of 15-20 mg/kg intraoperatively compared with 4 of 12 patients without the use of fluorescein. 5 These authors demonstrated progression-free survival of 7.2 months in the group who underwent fluorescence-guided resection versus 5.4 months in the group in whom conventional white-light resection was employed. However, the presence of WHO Grade II, III, and IV tumors in each of the study groups confounds the interpretation of the effect of fluorescein use in improving progression-free survival.…”

Section: Clinical Resultsmentioning

confidence: 99%

“…The use of a specific microscope-integrated camera for detection of fluorescein fluorescence may allow for a more accurate demarcation of tumor margins than tumor margins observed under white light or with the application of high doses of fluorescein without the use of an operating microscope, as reported in previous studies. 5,11,19,24 The use of lower doses of fluorescein also decreases the potential complications associated with higher doses. 7 Based on our analysis, the histopathological analysis of the fluorescent intraoperative samples correlated well with the laboratory in vivo findings.…”

Section: Clinical Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

166

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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Section: Clinical Resultsmentioning

confidence: 99%

Section: Clinical Resultsmentioning

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

166

148

View full text Add to dashboard Cite

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“…In addition, our data confirmed previously published series on the use of fluorescein for HGGs, showing a percentage of resection ranging from 75% to 100% (17-19, 21, 37-41). In some of these experiences, the fluorescein use was associated with a significant improvement of resection rate as compared with the use of white light illumination (21,37,38). It is also important to recognize that, even with fluorescein-guided technique and under specific filter visualization, a complete removal of favorable HGGs is not always possible.…”

Section: Discussionmentioning

confidence: 99%

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

Acerbi

Broggi

Schebesch

et al. 2018

Clinical Cancer Research

180

145

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Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUO-GLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported.Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18).Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm 3 (range, 1.3-87.8 cm 3 ). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%.Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs.

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“…Fluorescence imaging has been developed and tested as a tool to help guide the resection of high-grade gliomas (6,7). Despite encouraging results, this approach is not always reliable for identifying tumor tissue at the interface with normal tissue (8).…”

Section: Introductionmentioning

confidence: 99%

Label-Free Neurosurgical Pathology with Stimulated Raman Imaging

et al. 2016

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The goal of brain tumor surgery is to maximize tumor removal without injuring critical brain structures. Achieving this goal is challenging since it can be difficult to distinguish tumor from non-tumor tissue. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery as freezing, sectioning, and staining of the tissue require too much time. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of lipids and proteins within a fresh specimen. This information can be rendered into pathology-like images. Although this approach has been used to assess the density of glioma cells in murine orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors has not yet been fully evaluated with SRS imaging. Here we profile 41 specimens resected from 12 patients with a range of brain tumors. By evaluating large-scale stimulated Raman imaging data and correlating this data with current clinical gold standard of histopathology for 4,422 fields of view, we capture many essential diagnostic hallmarks for glioma classification. Notably, in fresh tumor samples we observe additional features, not seen by conventional methods, including extensive lipid droplets within glioma cells, collagen deposition in gliosarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendroglioma cells. This data is freely available in a public resource to foster diagnostic training and to permit additional interrogation. Our work establishes the methodology and provides a significant collection of reference images for label-free neurosurgical pathology.

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Gross Total Resection of Glioma with the Intraoperative Fluorescence-guidance of Fluorescein Sodium

Cited by 110 publications

References 23 publications

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

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

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

Label-Free Neurosurgical Pathology with Stimulated Raman Imaging

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