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5-氨基乙酰丙酸和荧光素钠双荧光引导手术治疗成人2级和3级弥漫性胶质瘤:112例回顾性分析

Double fluorescence-guided surgery with 5-ALA and fluorescein sodium in grade 2 and grade 3 adult-type diffuse gliomas: retrospective analysis of 112 cases.

作者信息

Bianconi Andrea, Bonada Marta, Zeppa Pietro, Bruno Francesco, La Cava Pietro, Panico Flavio, Rudà Roberta, Melcarne Antonio, Garbossa Diego, Cofano Fabio

机构信息

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.

出版信息

Brain Spine. 2025 May 9;5:104277. doi: 10.1016/j.bas.2025.104277. eCollection 2025.


DOI:10.1016/j.bas.2025.104277
PMID:40487874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145845/
Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

摘要

目的: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。 方法: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。 结果: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。 结论: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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/76339cc6f869/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/529f31ad1285/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/5ef156e29381/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/76339cc6f869/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/529f31ad1285/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/5ef156e29381/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3363/12145845/76339cc6f869/gr3.jpg

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[1]
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[3]
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[6]
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[8]
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[10]
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本文引用的文献

[1]
Enlightening the invisible: Applications, limits and perspectives of intraoperative fluorescence in neurosurgery.

Brain Spine. 2024-10-10

[2]
Intraoperative confocal laser endomicroscopy during 5-aminolevulinic acid-guided glioma surgery: significant considerations for resection at the tumor margin.

J Neurosurg. 2024-9-27

[3]
The oncological role of resection in newly diagnosed diffuse adult-type glioma defined by the WHO 2021 classification: a Review by the RANO resect group.

Lancet Oncol. 2024-9

[4]
Combined Fluorescence-Guided Surgery with 5-Aminolevulinic Acid and Fluorescein in Glioblastoma: Technical Description and Report of 100 Cases.

Cancers (Basel). 2024-8-6

[5]
Fluorescence-Guided Surgical Techniques in Adult Diffuse Low-Grade Gliomas: State-of-the-Art and Emerging Techniques: A Systematic Review.

Cancers (Basel). 2024-7-29

[6]
The Impact of Lateral Ventricular Opening in the Resection of Newly Diagnosed High-Grade Gliomas: A Single Center Experience.

Cancers (Basel). 2024-4-19

[7]
Can confocal laser endomicroscopy replace frozen section in diagnosis of brain tumors? A definite maybe.

Neuro Oncol. 2024-5-3

[8]
Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

Neuro Oncol. 2024-5-3

[9]
Advances in molecular and imaging biomarkers in lower-grade gliomas.

Expert Rev Neurother. 2023

[10]
Use of 5-ALA fluorescence-guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study.

J Neurosurg. 2024-4-1

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