|Nobuhiro Hata||Last modified date：2021.07.26|
Lecturer / Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University / Neurosurgery / Kyushu University Hospital
|1.||Hideyuki Arita, Yuko Matsushita, Ryunosuke Machida, Kai Yamasaki, Nobuhiro Hata, Makoto Ohno, Shigeru Yamaguchi, Takashi Sasayama, Shota Tanaka, Fumi Higuchi, Toshihiko Iuchi, Kuniaki Saito, Masayuki Kanamori, Ken ichiro Matsuda, Yohei Miyake, Kaoru Tamura, Sho Tamai, Taishi Nakamura, Takehiro Uda, Yoshiko Okita, Junya Fukai, Daisuke Sakamoto, Yasuhiko Hattori, Eriel Sandika Pareira, Ryusuke Hatae, Yukitomo Ishi, Yasuji Miyakita, Kazuhiro Tanaka, Shunsaku Takayanagi, Ryohei Otani, Tsukasa Sakaida, Keiichi Kobayashi, Ryuta Saito, Kazuhiko Kurozumi, Tomoko Shofuda, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Hikaru Sasaki, Masahiro Mizoguchi, Haruhiko Kishima, Mitsutoshi Nakada, Yukihiko Sonoda, Teiji Tominaga, Motoo Nagane, Ryo Nishikawa, Yonehiro Kanemura, Aya Kuchiba, Yoshitaka Narita, Koichi Ichimura, TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations, Acta Neuropathologica Communications, 10.1186/s40478-020-01078-2, 8, 1, 201-201, 2020.12, TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90–100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas..|
|2.||Osamu Togao, Toru Chikui, Kenji Tokumori, Yukiko Kami, Kazufumi Kikuchi, Daichi Momosaka, Yoshitomo Kikuchi, Daisuke Kuga, Nobuhiro Hata, Masahiro Mizoguchi, Koji Iihara, Akio Hiwatashi, Gamma distribution model of diffusion MRI for the differentiation of primary central nerve system lymphomas and glioblastomas, PLoS ONE, 10.1371/journal.pone.0243839, 15, 12 December, e0243839, 2020.12, The preoperative imaging-based differentiation of primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBs) is of high importance since the therapeutic strategies differ substantially between these tumors. In this study, we investigate whether the gamma distribution (GD) model is useful in this differentiation of PNCSLs and GBs. Twentyseven patients with PCNSLs and 57 patients with GBs were imaged with diffusion-weighted imaging using 13 b-values ranging from 0 to 1000 sec/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) <1.0×10-3 mm2/sec; f2, D >1.0×10-3 and <3.0×10-3 mm2/sec; f3, D >3.0 × 10-3 mm2/sec. The GD model-derived parameters were compared between PCNSLs and GBs. Receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. The correlations with intravoxel incoherent motion (IVIM)-derived parameters were evaluated. The PCNSL group's κ (2.26 ± 1.00) was significantly smaller than the GB group's (3.62 ± 2.01, p = 0.0004). The PCNSL group's f1 (0.542 ± 0.107) was significantly larger than the GB group's (0.348 ± 0.132, p<0.0001). The PCNSL group's f2 (0.372 ± 0.098) was significantly smaller than the GB group's (0.508 ± 0.127, p<0.0001). The PCNSL group's f3 (0.086 ± 0.043) was significantly smaller than the GB group's (0.144 ± 0.062, p<0.0001). The combination of κ, f1, and f3 showed excellent diagnostic performance (area under the curve, 0.909). The f1 had an almost perfect inverse correlation with D. The f2 and f3 had very strong positive correlations with D and f, respectively. The GD model is useful for the differentiation of GBs and PCNSLs..|
|3.||Yuhei Sangatsuda, Fumihito Miura, Hiromitsu Araki, Masahiro Mizoguchi, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Takeo Amemiya, Yutaka Fujioka, Yasuhito Arai, Akihiko Yoshida, Tatsuhiro Shibata, Koji Yoshimoto, Koji Iihara, Takashi Ito, Base-resolution methylomes of gliomas bearing histone H3.3 mutations reveal a G34 mutant-specific signature shared with bone tumors, SCIENTIFIC REPORTS, 10.1038/s41598-020-73116-x, 10, 1, 16162-16162, 2020.09, Two recurrent mutations, K27M and G34R/V, in H3F3A, encoding non-canonical histone H3.3, are reported in pediatric and young adult gliomas, whereas G34W mutation is prevalent in bone tumors. In contrast to K27M mutation, it remains elusive how G34 mutations affect the epigenome. Here we performed whole-genome bisulfite sequencing of four G34R-mutated gliomas and the G34V-mutated glioma cell line KNS-42 for comparison with gliomas harboring K27M and no mutations in H3F3A and with G34W-mutated bone tumors. G34R-mutated gliomas exhibited lower global methylation levels, similar CpG island (CGI) methylation levels, and compromised hypermethylation of telomere-proximal CGIs, compared to the other two glioma subgroups. Hypermethylated regions specific to G34R-mutated gliomas were enriched for CGIs, including those of OLIG1, OLIG2, and canonical histone genes in the HIST1 cluster. They were notably hypermethylated in osteosarcomas with, but not without, G34W mutation. Independent component analysis revealed that G34 mutation-specific components shared a significant similarity between glioma and osteosarcoma, suggesting that G34 mutations exert characteristic methylomic effects regardless of the tumor tissue-of-origin. CRISPR/Cas9-mediated disruption of G34V-allele in KNS-42 cells led to demethylation of a subset of CGIs hypermethylated in G34R-mutated gliomas. These findings will provide a basis for elucidating epigenomic roles of G34 oncohistone in tumorigenesis..|
|4.||Shoko Sadashima, Satoshi O. Suzuki, Hironori Haruyama, Nobutaka Mukae, Yutaka Fujioka, Nobuhiro Hata, Masahiro Mizoguchi, Keisuke Ishimatsu, Akio Hiwatashi, Toru Iwaki, A juvenile case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation, Neuropathology, 10.1111/neup.12693, 40, 6, 646-650, 2020.12, Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF mutation, the first case reported in a glioma. BRAF is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention. A598T A598T.|
|5.||Yutaka Fujioka, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yuhei Michiwaki, Takeo Amemiya, Kosuke Takigawa, Yusuke Funakoshi, Aki Sako, Toru Iwaki, Koji Iihara, Masahiro Mizoguchi, Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid, Journal of Neuro-Oncology, 10.1007/s11060-020-03682-7, 152, 1, 47-54, 2021.03, Purpose: Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). Methods: CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. Results: We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. Conclusion: We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas. ®.|
|6.||Takeo Amemiya, Nobuhiro Hata, Masahiro Mizoguchi, Ryuji Yokokawa, Yoichiro Kawamura, Ryusuke Hatae, Yuhei Sangatsuda, Daisuke Kuga, Yutaka Fujioka, Kosuke Takigawa, Yojiro Akagi, Koji Yoshimoto, Koji Iihara, Takashi Miura, Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device, Molecular Biology Reports, 10.1007/s11033-020-06061-7, 48, 1, 395-403, 2021.01, High vascularization is a biological characteristic of glioblastoma (GBM); however, an in-vitro experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature de-novo vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets..|
|7.||Kikuchi K, Hiwatashi A, Togao O, Yamashita K, Kamei R, Momosaka D, Hata N, Iihara K, Suzuki SO, Iwaki T, Honda H., Intravoxel Incoherent Motion MR Imaging of Pediatric Intracranial Tumors: Correlation with Histology and Diagnostic Utility., AJNR Am J Neuroradiol. 40(5):878-884, 2019. , 10.3174/ajnr.A6052., 40, 5, 878-884, 2019.05.|
|8.||Yusuke Funakoshi, Tadahisa Shono, Ai Kurogi, Naoki Maehara, Nobuhiro Hata, Masahiro Mizoguchi, Intraoperative Tissue Expansion Using a Foley Catheter for a Scalp Defect Technical Note, World Neurosurgery, 10.1016/j.wneu.2020.07.096, 143, 62-67, 2020.11, Background: Primary closure of the surgical wound during neurosurgical procedures is sometimes difficult because of limited ability to expand the scalp, or because the skin defect is large. Hence, our institution recently adopted the technique of intraoperative tissue expansion using a Foley catheter for these cases. We describe this easily accomplished, readily available, effective, economical technique and describe our experience performing the technique. Methods: With this procedure, the subcutaneous tissue (usually the subperiosteal layer) surrounding the skin defect is dissected to make a subcutaneous pocket in which to place a 20-French Foley catheter. The standard expander is a 30-mL balloon. The catheter is inserted into the subcutaneous pocket, and the balloon is inflated with 10–30 mL of saline for 5 minutes, after which the balloon is deflated for 3 minutes in a cyclic loading manner. After sufficient expansion, the primary closure of the surgical wound is achieved with minimal tension on the surrounding skin. Results: Between November 2018 and February 2020, we performed this technique in 5 patients, each with a large surgical defect in the scalp. Primary closure was achieved, and postoperative wound healing was excellent in all 5 patients. Conclusions: Intraoperative skin expansion using a Foley catheter—which is easily performed, readily available, and economical—can be used to achieve surgical wound closure during various neurosurgical procedures..|
|9.||Hata N, Hisada K, Torisu R, Suzuki SO, Kameda K, Sasaki T., Foreign body granuloma associated with dura-cranioplasty after resection of convexity meningioma with extracranial extension: case report., Neurol Med Chir (Tokyo), 51, 3, 236-238, 2011.03.|
|10.||Masaoki Kusunoki, Kazufumi Kikuchi, Osamu Togao, Koji Yamashita, Daichi Momosaka, Yoshitomo Kikuchi, Daisuke Kuga, Nobuhiro Hata, Masahiro Mizoguchi, Koji Iihara, Satoshi O. Suzuki, Toru Iwaki, Yuta Akamine, Akio Hiwatashi, Differentiation of high-grade from low-grade diffuse gliomas using diffusion-weighted imaging
a comparative study of mono-, bi-, and stretched-exponential diffusion models, Neuroradiology, 10.1007/s00234-020-02456-2, 62, 7, 815-823, 2020.07, Purpose: Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models’ ability to differentiate between high-grade and low-grade gliomas. Methods: This retrospective study included 22 patients with diffuse gliomas (age, 23–74 years; 12 males; 11 high-grade and 11 low-grade gliomas) who underwent preoperative 3 T-magnetic resonance imaging from October 2014 to August 2019. The apparent diffusion coefficient was calculated from the mono-exponential model. Using 13 b-values, the true-diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction were obtained from the bi-exponential model, and the distributed-diffusion coefficient and heterogeneity index were obtained from the stretched-exponential model. Region-of-interests were drawn on each imaging parameter map for subsequent histogram analyses. Results: The skewness of the apparent diffusion, true-diffusion, and distributed-diffusion coefficients was significantly higher in high-grade than in low-grade gliomas (0.67 ± 0.67 vs. − 0.18 ± 0.63, 0.68 ± 0.74 vs. − 0.08 ± 0.66, 0.63 ± 0.72 vs. − 0.15 ± 0.73; P = 0.0066, 0.0192, and 0.0128, respectively). The 10th percentile of the heterogeneity index was significantly lower (0.77 ± 0.08 vs. 0.88 ± 0.04; P = 0.0004), and the 90th percentile of the perfusion fraction was significantly higher (12.64 ± 3.44 vs. 7.14 ± 1.70%: P < 0.0001), in high-grade than in low-grade gliomas. The combination of the 10th percentile of the true-diffusion coefficient and 90th percentile of the perfusion fraction showed the best area under the receiver operating characteristic curve (0.96). Conclusion: The bi-exponential model exhibited the best diagnostic performance for differentiating high-grade from low-grade gliomas..
|12.||Kai Yamasaki, Chikako Kiyotani, Keita Terashima, Yuko Watanabe, Masayuki Kanamori, Yuhki Koga, Nobuhiro Hata, Fuminori Iwasaki, Hiroaki Goto, Katsuyoshi Koh, Jun Kurihara, Shinya Tokunaga, Yoshiki Arakawa, Daiichiro Hasegawa, Yoshiyuki Kosaka, Junichi Hara, Clinical characteristics, treatment, and survival outcome in pediatric patients with atypical teratoid/rhabdoid tumors
A retrospective study by the Japan Children’s Cancer Group, Journal of Neurosurgery: Pediatrics, 10.3171/2019.9.PEDS19367, 25, 2, 111-120, 2020.01, OBJECTIVE The prognosis of atypical teratoid/rhabdoid tumors (ATRTs) has improved in recent years with the use of multimodal therapy, mainly in cases not involving metastatic disease. The authors wanted to obtain historical control data and evaluate the suitable treatments in Japanese children with ATRTs that were proven negative for INI-1 immunostaining. METHODS The authors retrospectively collected clinical information on 38 pediatric patients with ATRTs treated from 2005 to 2016 and analyzed the data for this series. RESULTS The median age of the patient population was 1.3 years, and the male/female ratio was approximately 2:1. Twenty-three patients (60.5%) had metastases. The effects of treatment on prognosis were analyzed for 34 patients after exclusion of 4 patients who could not receive curative treatment. At a median follow-up of 40.9 months, the mean (± SD) progression-free survival (PFS) and overall survival (OS) were 66.6% ± 8.3% and 45.9% ± 8.7% at 2 years and 44.2% ± 9.9% and 34.2% ± 8.9% at 5 years, respectively. The metastasis stage at diagnosis (M0–1 vs M2–4) (HR 2.68, 95% CI 1.08–6.65; p = 0.0338) and gross tumor resection (yes vs no) (HR 3.49, 95% CI 1.01–12.1; p = 0.0481) were prognostic factors for PFS but not for OS. Postoperative chemotherapy was performed in all 34 cases. High-dose chemotherapy was performed in 19 (55.8%) of 34 patients and showed a positive impact on OS (HR 0.31, 95% CI 0.11–0.86; p = 0.0254); the most commonly used regimen was a double-conditioning regimen of thiotepa plus melphalan. Local radiotherapy had a positive impact on both PFS and OS; however, craniospinal irradiation (CSI) performed in 12 patients as the primary therapy was associated with a poor outcome. Disseminated recurrence within 12 months from diagnosis was the most common pattern of treatment failure regardless of CSI. CONCLUSIONS There has been an improvement in outcomes for pediatric ATRT patients since the introduction of multimodal therapy in Japan, mainly in patients without metastases. Even if selection bias is taken into consideration, CSI did not contribute to an improved prognosis. Novel treatment approaches are required for pediatric ATRT patients with metastases..