Ichiyo Shibahara1, Yukiko Shibahara2, Hiroyuki Hagiwara3, Takashi Watanabe4, Yasushi Orihashi5, Hajime Handa6, Madoka Inukai6,2, Takuichiro Hide6, Yoshie Yasui6, Toshihiro Kumabe6. 1. Department of Neurosurgery, Kitasato University School of Medicine, 1-15-1 Kitasato Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan. shibahar@med.kitasato-u.ac.jp. 2. Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. 3. Department of Neurosurgery, Yamato Municipal Hospital, Yamato, Kanagawa, Japan. 4. Department of General Internal Medicine, JCHO Sendai Hospital, Sendai, Miyagi, Japan. 5. Division of Clinical Research, Kitasato University Hospital, Sagamihara, Kanagawa, Japan. 6. Department of Neurosurgery, Kitasato University School of Medicine, 1-15-1 Kitasato Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Jessin K John; Adam M Robin; Aqueel H Pabaney; Richard A Rammo; Lonni R Schultz; Neema S Sadry; Ian Y Lee Journal: J Neurosurg Date: 2016-11-04 Impact factor: 5.115
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