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术中肿瘤荧光的客观评估揭示了胶质母细胞瘤内的生物学异质性:一项生物计量学研究。

Objective assessment of intraoperative tumor fluorescence reveals biological heterogeneity within glioblastomas: a biometric study.

机构信息

Division of Neurosurgery, Department of Surgical Oncology, Tata Memorial Centre, Homi Bhabha National University, 1221, Homi Bhabha Block, Mumbai, India.

Department of Surgical Pathology, Tata Memorial Centre, Homi Bhabha National University, Mumbai, India.

出版信息

J Neurooncol. 2020 Feb;146(3):477-488. doi: 10.1007/s11060-019-03338-1. Epub 2020 Feb 4.

DOI:10.1007/s11060-019-03338-1
PMID:32020478
Abstract

PURPOSE

Heterogeneity within GBMs and variability of visualized fluorescence combine to confer practical limitations to the technique of optical imaging. A biometric analysis was planned to objectively ascertain and analyse this phenomenon METHODS: 25 adult glioblastoma subjects undergoing resection were prospectively accrued. Biopsies were taken from various parts of the tumor and safe peritumoral zones. White light (WL) and visualized fluorescence was subjectively recorded. Corresponding histopathology [coalescent (C) or infiltrating (I) tumor] and protoporphyrin-IX (PPIX) levels were assayed.

RESULTS

WL was very sensitive for detecting tumor. SF was more specific and had high positive predictive value for detecting tumor. WF on the other hand had a poor discriminatory efficacy. Mean PPIX levels were 3.0, 2.01 and 0.16 for SF, WF, and NF respectively. WF had a wide variable range of PPIX levels. Within the coalescent tumor areas, there was a variable distribution of fluorescence (both subjective as well as objective PPIX levels) with only 54% samples showing SF and high PPIX. In seven cases this discordance was noted within the same tumor (biological heterogeneity).

CONCLUSIONS

Fluorescence may miss important tumor areas even if objective assessment is used. Histologically similar tumor areas may exhibit contrasting fluorescence properties, a phenomenon which needs further investigation and elucidation of underlying mechanisms which could potentially be manipulated to optimize the utility of fluorescence guidance.

摘要

目的

GBM 内的异质性和可视化荧光的可变性结合起来,为光学成像技术带来了实际的限制。计划进行生物计量分析,以客观地确定和分析这种现象。

方法

前瞻性地纳入了 25 名接受切除手术的成年胶质母细胞瘤患者。从肿瘤的不同部位和安全的肿瘤周围区域采集活检。主观记录白光(WL)和可视化荧光。检测相应的组织病理学[融合(C)或浸润(I)肿瘤]和原卟啉-IX(PPIX)水平。

结果

WL 对检测肿瘤非常敏感。SF 对检测肿瘤具有更高的特异性和高阳性预测值。WF 另一方面则具有较差的区分效果。SF、WF 和 NF 的平均 PPIX 水平分别为 3.0、2.01 和 0.16。WF 的 PPIX 水平变化范围很广。在融合肿瘤区域内,荧光存在可变分布(主观和客观 PPIX 水平均如此),只有 54%的样本显示 SF 和高 PPIX。在 7 例中,同一肿瘤内存在这种不一致性(生物学异质性)。

结论

即使使用客观评估,荧光也可能会错过重要的肿瘤区域。组织学上相似的肿瘤区域可能表现出相反的荧光特性,这种现象需要进一步研究和阐明潜在的机制,这些机制可能会被操纵以优化荧光引导的效用。

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Neurosurg Rev. 2018 Jan;41(1):3-18. doi: 10.1007/s10143-016-0745-4. Epub 2016 May 25.
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What is the Surgical Benefit of Utilizing 5-Aminolevulinic Acid for Fluorescence-Guided Surgery of Malignant Gliomas?使用5-氨基乙酰丙酸进行恶性胶质瘤荧光引导手术的外科手术益处是什么?
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