Department of Neurosurgery, Kitasato University School of Medicine, 1-15-1 Kitasato Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
J Neurooncol. 2022 Sep;159(2):425-435. doi: 10.1007/s11060-022-04078-5. Epub 2022 Jul 8.
Opening the ventricular system during glioblastoma surgery is often necessary, but the consequent effect on the tumor microenvironment of glioblastoma remains unknown. Implantation of carmustine wafer enables direct drug delivery to the tumor site; however, the exact mechanism of the wafer's biodegradation process is unclear, and the available data is limited to in vivo non-human mammalian studies. We hypothesized that the ventricular opening affects the degradation process of the wafer and the glioblastoma tumor microenvironment.
This study included 30 glioblastoma patients. 21 patients underwent carmustine wafer implantation during initial surgery. All patients underwent repeated surgical resection upon recurrence, allowing for pathological comparison of changes associated with wafer implantation. Immunohistochemical analyses were performed using CD68, TMEM119, CD163, IBA1, BIN1, and CD31 antibodies to highlight microglia, macrophages, and tumor vascularity, and the quantitative scoring results were correlated with clinical, molecular, and surgical variables, including the effect of the ventricular opening.
The carmustine wafer implanted group presented significantly less TMEM119-positive microglia within the tumor (P = 0.0002). Simple and multiple regression analyses revealed that the decrease in TMEM119-positive microglia was correlated with longer intervals between surgeries and opened ventricular systems. No correlation was observed between age, methylated O6-methylguanine DNA methyltransferase promoter expression, and the extent of surgical resection.
Our study findings strongly suggest that biomaterials may possess immunomodulation capacity, which is significantly impacted by the ventricular opening procedure. Furthermore, our data highlights the pathophysiological effects of the ventricular opening within the surrounding human brain, especially after the wafer implantation.
在胶质母细胞瘤手术中打开脑室系统通常是必要的，但由此对胶质母细胞瘤肿瘤微环境的影响尚不清楚。卡莫司汀植入物的植入使药物能够直接递送到肿瘤部位；然而，关于植入物的生物降解过程的确切机制尚不清楚，并且可用的数据仅限于体内非人类哺乳动物研究。我们假设脑室开口会影响植入物的降解过程和脑肿瘤肿瘤微环境。
本研究纳入了 30 名胶质母细胞瘤患者。21 名患者在初次手术时接受了卡莫司汀植入物植入。所有患者在复发时均接受了重复手术切除，允许对与植入物植入相关的变化进行病理比较。使用 CD68、TMEM119、CD163、IBA1、BIN1 和 CD31 抗体进行免疫组织化学分析，以突出小胶质细胞、巨噬细胞和肿瘤血管生成，并将定量评分结果与临床、分子和手术变量相关联，包括脑室开口的影响。
植入卡莫司汀植入物的患者肿瘤内 TMEM119 阳性小胶质细胞明显减少（P=0.0002）。简单和多元回归分析表明，TMEM119 阳性小胶质细胞的减少与手术间隔时间和打开的脑室系统之间存在相关性。年龄、甲基化 O6-甲基鸟嘌呤 DNA 甲基转移酶启动子表达和手术切除范围与 TMEM119 阳性小胶质细胞减少之间无相关性。
我们的研究结果强烈表明，生物材料可能具有免疫调节能力，而这种能力受到脑室开口程序的显著影响。此外，我们的数据突出了脑室开口在周围人脑内的病理生理影响，尤其是在植入物植入后。
