Yoneda Takashi, Nonoguchi Naosuke, Ikeda Naokado, Yagi Ryokichi, Kawabata Shinji, Furuse Motomasa, Hirose Yoshinobu, Kuwabara Hiroko, Tamura Yoji, Kajimoto Yoshinaga, Kuroiwa Toshihiko
1 Department of Neurosurgery, Osaka Medical College , Takatsuki, Japan .
2 Department of Pathology, Osaka Medical College , Takatsuki, Japan .
Photomed Laser Surg. 2018 May;36(5):266-272. doi: 10.1089/pho.2017.4384. Epub 2018 Feb 26.
This study is intended to objectively clarify the relationship between the fluorescence intensity emitted by protoporphyrin IX (PpIX), which is a metabolite of 5-aminolevulinic acid (ALA), and histological findings during glioblastoma surgery.
ALA is widely used for the intraoperative detection of tumors. There are several reports about the fluorescence of PpIX and the histological findings of tumors, but judgments about the fluorescence intensity depend largely on the subjective sense of each surgeon.
We quantified the PpIX fluorescence intensity emitted from tissue specimens using a spectroradiometer and evaluated the relationship between a spectral radiance of 635 nm and the histopathological features of surgical specimens of glioblastoma. Surgical samples from glioblastoma patients consist of a strongly fluorescent area (SFA) or vaguely fluorescent area (VFA). Hematoxylin and eosin staining, immunohistochemical Ki-67, and CD31 staining were performed to evaluate the cell density, MIB-1 index, and vascularity, respectively. The fluorescence intensities of each sample were compared with each histopathological parameter.
Cell density, MIB-1 index, and total vascular area were significantly correlated with PpIX fluorescence radiance. 87.5% of SFA were judged to be tumor bulk consisting mostly of tumor cells and 12.5% peritumoral invaded brain. In the VFA, 100% of specimens were judged to be peritumoral invaded brain.
ALA-induced PpIX fluorescence has quantitatively correlated well with histopathological malignant features both in SFA and VFA. These findings suggest that not only SFA but also VFA should be removed to the highest extent that does not cause neurological symptoms.
本研究旨在客观阐明5-氨基酮戊酸（ALA）的代谢产物原卟啉IX（PpIX）发出的荧光强度与胶质母细胞瘤手术期间组织学结果之间的关系。
ALA广泛用于肿瘤的术中检测。关于PpIX的荧光和肿瘤的组织学结果有若干报道，但对荧光强度的判断很大程度上取决于每位外科医生的主观感受。
我们使用分光辐射计对组织标本发出的PpIX荧光强度进行定量，并评估635nm的光谱辐射率与胶质母细胞瘤手术标本的组织病理学特征之间的关系。胶质母细胞瘤患者的手术样本包括强荧光区（SFA）或模糊荧光区（VFA）。分别进行苏木精和伊红染色、免疫组织化学Ki-67和CD31染色，以评估细胞密度、MIB-1指数和血管生成情况。将每个样本的荧光强度与每个组织病理学参数进行比较。
细胞密度、MIB-1指数和总血管面积与PpIX荧光辐射率显著相关。87.5%的SFA被判定为主要由肿瘤细胞组成的肿瘤块，12.5%为瘤周浸润脑。在VFA中，100%的标本被判定为瘤周浸润脑。
ALA诱导的PpIX荧光在SFA和VFA中均与组织病理学恶性特征在数量上有良好的相关性。这些发现表明，不仅SFA，而且VFA都应在不引起神经症状的最大程度上予以切除。
