Bianconi Andrea, Bonada Marta, Zeppa Pietro, Bruno Francesco, La Cava Pietro, Panico Flavio, Rudà Roberta, Melcarne Antonio, Garbossa Diego, Cofano Fabio
Division of Neurosurgery, "Città della Salute e della Scienza" University Hospital, Department of Neuroscience "Rita Levi Montalcini", University of Turin, 10124, Turin, Italy.
Division of Neuro-Oncology, "Città della Salute e della Scienza" University Hospital, Department of Neuroscience "Rita Levi Montalcini", University of Turin, 10124, Turin, Italy.
Brain Spine. 2025 May 9;5:104277. doi: 10.1016/j.bas.2025.104277. eCollection 2025.
Fluorescence-guided surgery (FGS) has been increasingly used to support glioma surgery to obtain a maximal extent of resection (EOR). Current evidence in lower-grade gliomas does not support the routine use of FGS obtained with the most common fluorescence agents (e.g. 5-ALA and fluorescein sodium). However, the combination of these two dyes has not been extensively explored yet. Main objective of this study is to evaluate the role of 5-ALA and FS in LGGs surgery for tumor detection, margin definition, and prognostic relevance.
112 patients affected by a histologically confirmed adult-type diffuse glioma grade 2-3 molecularly defined underwent craniotomy in "Città della Salute e della Scienza" hospital (Turin, Italy). Surgery has been performed under general anesthesia with the previous administration of both 5-ALA (20 mg/kg) and fluorescein sodium (3 mg/kg). We retrospectively investigated clinical, radiological, histological and molecular data. Fluorescence positive rate and pattern have been reported both for 5-ALA and for fluoresceine.
We included 69 patients with astrocytoma mutant and 43 with oligodendroglioma mutant 1p19q-codeleted. Seventeen cases were positive for both 5-ALA and FS (15.1 %), 24 for 5-ALA (21.4 %) only, 1 for FS (1.0 %) only, 70 were negative (62.5 %). The relationship between intraoperative fluorescence and the presence of foci with contrast enhancement uptake on the preoperative MRI was statistically significant (p < 0.001) for both the dyes. 5-ALA intraoperative detection had a statistically significant impact on the overall survival (OS) (HR: 2.51, 95 % CI: 1.25-5.01, p = 0.009) and progression-free survival (PFS) (HR: 2.46, 95 % CI: 1.34-4.52, p = 0.004). Additionally, both FS and 5-ALA fluorescence slightly prevailed in grade 3 gliomas, especially 5-ALA.
The results achieved in this study do not support the role of 5-ALA and FS to intraoperatively define the extent of resection, because of low fluorescence rates. Nevertheless, 5-ALA expression could be used to intraoperatively identify more aggressive foci and add useful prognostic information before the histological analysis. Indeed, FS is mostly related to blood-brain barrier damage and, thus, with contrast enhancement in MRI.
荧光引导手术（FGS）已越来越多地用于辅助胶质瘤手术以实现最大程度的切除（EOR）。目前关于低级别胶质瘤的证据不支持常规使用最常见的荧光剂（如5-氨基乙酰丙酸和荧光素钠）进行FGS。然而，这两种染料的联合应用尚未得到广泛研究。本研究的主要目的是评估5-氨基乙酰丙酸和荧光素钠在低级别胶质瘤手术中对肿瘤检测、边界界定及预后相关性的作用。
112例经组织学确诊为2-3级分子定义的成人型弥漫性胶质瘤患者在意大利都灵“健康与科学城”医院接受开颅手术。手术在全身麻醉下进行，术前给予5-氨基乙酰丙酸（20mg/kg）和荧光素钠（3mg/kg）。我们回顾性研究了临床、放射学、组织学和分子数据。报告了5-氨基乙酰丙酸和荧光素的荧光阳性率及模式。
我们纳入了69例星形细胞瘤突变型患者和43例少突胶质细胞瘤1p19q共缺失突变型患者。17例患者5-氨基乙酰丙酸和荧光素钠均呈阳性（15.1%），24例仅5-氨基乙酰丙酸呈阳性（21.4%），1例仅荧光素钠呈阳性（1.0%），70例呈阴性（62.5%）。两种染料术中荧光与术前MRI上对比增强灶的存在之间的关系均具有统计学意义（p<0.001）。5-氨基乙酰丙酸术中检测对总生存期（OS）（HR：2.51，95%CI：1.25-5.01，p=0.009）和无进展生存期（PFS）（HR：2.46，95%CI：1.34-4.52，p=0.004）有统计学显著影响。此外，荧光素钠和5-氨基乙酰丙酸的荧光在3级胶质瘤中略占优势，尤其是5-氨基乙酰丙酸。
由于荧光率较低，本研究结果不支持5-氨基乙酰丙酸和荧光素钠在术中界定切除范围的作用。然而，5-氨基乙酰丙酸的表达可用于术中识别更具侵袭性的病灶，并在组织学分析前提供有用的预后信息。实际上，荧光素钠主要与血脑屏障破坏有关，因此与MRI中的对比增强有关。
