Maugeri Rosario, Villa Alessandro, Pino Mariangela, Imperato Alessia, Giammalva Giuseppe Roberto, Costantino Gabriele, Graziano Francesca, Gulì Carlo, Meli Francesco, Francaviglia Natale, Iacopino Domenico Gerardo
Department of Experimental Biomedicine and Clinical Neurosciences, School of Medicine, Postgraduate Residency Program in Neurological Surgery, Neurosurgical Clinic, AOUP "Paolo Giaccone", 90100 Palermo, Italy.
Division of Neurosurgery, ARNAS Civico Hospital, 90100 Palermo, Italy.
Brain Sci. 2018 Feb 7;8(2):31. doi: 10.3390/brainsci8020031.
High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.
高级别胶质瘤(HGGs)是成人中最常见的原发性恶性脑肿瘤,患者在确诊后两年内会死亡。作为多模式治疗的第一步,最大程度安全切除恶性胶质瘤是恶性胶质瘤手术中公认的目标。全切除在提高总生存期(OS)和无进展生存期(PFS)方面具有重要作用,但在高级别胶质瘤中确定肿瘤边界特别困难。因此,已提出使用成像辅助手段,如5-氨基乙酰丙酸(5-ALA)或荧光素钠(FS),作为更好地界定高级别胶质瘤手术切除范围的更优策略。5-氨基乙酰丙酸(5-ALA)被认为是血红素合成途径的前体。原卟啉IX(PpIX)是血红素代谢的中间化合物,在适当波长的光激发下会产生荧光。恶性胶质瘤细胞在外源性给予5-ALA后具有选择性合成或积累5-ALA衍生卟啉的能力。另一方面,荧光素钠(FS)是一种荧光物质,它并非肿瘤细胞所特有,实际上它是血脑屏障(BBB)受损区域的标志物。其有效性已通过多中心II期试验(FLUOGLIO)得到证实,但缺乏随机III期试验数据。我们对文献进行了分析性综述,目的是确定5-ALA和FS在成年患者高级别胶质瘤手术中的有用性。