Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature
- Division of Neurosurgery, ARNAS Civico Hospital, Palermo, Italy
- Department of Experimental Biomedicine and Clinical Neurosciences, School of Medicine, Neurosurgical Clinic, AOUP “Paolo Giaccone”, Palermo, Italy
Department of Experimental Biomedicine and Clinical Neurosciences, School of Medicine, Neurosurgical Clinic, AOUP “Paolo Giaccone”, Palermo, Italy
DOI:10.4103/sni.sni_89_17Copyright: © 2017 Surgical Neurology International This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Natale Francaviglia, Domenico Gerardo Iacopino, Gabriele Costantino, Alessandro Villa, Pietro Impallaria, Francesco Meli, Rosario Maugeri. Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature. 11-Jul-2017;8:145
How to cite this URL: Natale Francaviglia, Domenico Gerardo Iacopino, Gabriele Costantino, Alessandro Villa, Pietro Impallaria, Francesco Meli, Rosario Maugeri. Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature. 11-Jul-2017;8:145. Available from: http://surgicalneurologyint.com/surgicalint-articles/fluorescein-for-resection-of-high%e2%80%91grade-gliomas-a-safety-study-control-in-a-single-center-and-review-of-the-literature/
Background:The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data.
Methods:Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27–86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively.
Results:Gross total resection (GTR) was achieved in 53.2% (n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% (n = 14), while a partial resection (PR) (n = 8) of patients. Overall, in 83% (n = 39) of patients who underwent fluorescence-guided surgery the resection rate achieved was >95%. No adverse effects correlated to fluorescein have been recorded.
Conclusion:Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas.
Keywords: 5-aminolevulinic acid, extent of resection, fluorescein sodium, high-grade gliomas, YELLOW 560 filter
Gliomas are the most common primary malignant brain tumors in adults, nearly represent 80%, with poor prognosis in their high-grade forms.[
In this retrospective study, after the approval of Local Ethic Committee, we collected data of 47 patients (25 males, 22 females; mean age: 60.3 years, range: 27–86 years). All patients had been surgically treated at the Neurosurgical Unit of ARNAS Civico Hospital, between September 2015 and November 2016 [
In all cases 5 mg/kg body weight of FS was injected intravenously via the central venous line, after the induction of anesthesia. Vital signs were monitored for 15 min. Under white light, no fluorescent effect was detected. The fluorescent dye was visible under the YELLOW 560 nm filter, on the OPMI Pentero 900 surgical microscope (Carl Zeiss Meditec, Oberkochen, Germany). The fluorescence shaped the vital tumor margins [
Intraoperative view of a right frontal glioblastoma under normal white xenon-light illumination (a) and at the beginning of tumor removal under the YELLOW 560 nm filter (b). During tumor removal on the Pentero 900 surgical microscope, there is a clear delineation of the tumor area which shows significant fluorescein sodium enhancement revealing the boundary between the bright yellow tumor and the surrounding brain (c); at the end of the removal, no residual tumor tissue is evident (d)
Pre- and postoperative clinical assessment
Each patient general physical performance was recorded using the KPS. The median preoperative KPS score was 85.1 (range: 70–100). Preoperative clinical evaluation was performed at the admission to the neurosurgical unit. A second evaluation was conducted during the postoperative course, on discharge and at the first outpatient clinic visit approximately 1 month later. The neurological exam was evaluated by a neurologist. Surgery was followed by radiotherapy with concomitant and adjuvant temozolomide in 85.1% of cases, according to the Stupp protocol.[
Postoperatively, the extent of tumor resection was identified by 35 contrast enhanced T1 weighted MRI and 12 contrast enhanced computed tomography (CT scan), 72 h after surgery. Three categories were distinguished: no residual tumor tissue = gross total resection (GTR); minimal residual tumor tissue = subtotal resection (STR) and partial resection (PR). GTR was defined as resection where no residual enhanced tumor is visible, STR was defined as nearly total (>95%), PR as <95%. Postoperative tumor volumes after surgery were calculated using an open-source, free medical image viewer software (OsiriX for Mac) on enhanced residual tissue (in T1 weighted MRI or CT scan) [Figures
Histological analyses were performed with standard procedures. The classification was conducted on the basis of the current WHO classification of tumors of the central nervous system.
The average duration of the surgical procedure (“skin to skin”) was 175.5 min (range: 108–316 min); the median length of hospital stay was 20 days (range: 8–73 days). Patients and tumor data and results are summarized in Tables
The importance of radical resection in glioma surgery has been already stressed in literature. Although rare cases of spontaneous regression of benign tumors after incomplete removal are described,[
In our experience, the use of FS together with YELLOW 560 nm filter has been found “helpful” in tumor removal in all the surgical procedures, allowing a better visual discrimination between the pinkish brain tissue and the yellow stained tumor tissue. This also seemed to be more comfortable to the surgeon eyes. The enhancement of tumoral tissue, which corresponds to the contrast enhancement of preoperative MRI, was visible immediately after dural opening, usually 30 min after the FS administration, and lasted until the end of tumor removal. The rate of tumor removal in our study was similar to that of previous studies. GTR was achieved in 53.2% (n = 25) of patients. A STR (>95%) was achieved in 29.8% (n = 14) of them, while a PR (<95%) was obtained in 17% (n = 8) of patients. Globally, a resection >95% was achieved in 83% (n = 39) of patients who underwent fluorescence-guided surgery. Moreover, FS seemed to be safe and effective in the intraoperative visual phase by distinguishing tumor from normal brain tissue and in the postoperative neuroimaging control. The resection was also maximized with the aid of neuronavigation system in eloquent areas, trying to avoid additional neurological deficit to the patient. The median postoperative KPS score was 83.4 (range: 50–100). Comparing pre- and postoperative scores, the latter was found higher in 15 patients, lower in 11, and stable in 21 patients. As in Schebesch, Acerbi, and Hamamcıoğlu series, we also report the use of low dose FS about 2 mL (5 mg/kg body weight). This low dose, together with YELLOW 560 nm filter, allowed an easier intraoperative management than higher doses of FS or 5-ALA, without the need to wait for the dye peak.[
The intraoperative identification and resection of HGGs is a significant and important challenge in neurosurgery. In our series fluorescence-guided surgery of HGGs using FS has been a good tool in achieving GTR and in distinguishing tumoral by normal brain tissue. Larger-scale studies are now needed, to quantify the efficacy of fluorescein-guided surgery in improving the extent of resection as well as the progression-free and overall patient survival.
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Conflicts of interest
There are no conflicts of interest.
No financial support was received. The manuscript or parts of it are not under consideration by another journal or electronic publication and have not been previously published or presented at a meeting. The authors have no proprietary or commercial interest in any materials or method discussed in this article.
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