研究者業績
基本情報
研究分野
1経歴
15-
2022年4月 - 現在
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2022年2月 - 現在
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2010年4月 - 現在
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2019年4月 - 2023年7月
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2014年2月 - 2022年1月
学歴
1-
1981年4月 - 1987年3月
委員歴
9-
2021年10月 - 現在
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2018年9月 - 現在
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2014年5月 - 現在
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2010年10月 - 現在
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2018年12月 - 2020年11月
論文
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World neurosurgery 126 e1042-e1049 2019年6月 査読有りOBJECTIVE: c-Met has been shown to be associated with tumor growth in several human cancers. This study aims to evaluate the correlation between the c-Met expression and histopathologic/clinical characteristics. METHODS: A total of 153 patients with histologically defined World Health Organization grade II-IV diffuse astrocytic and oligodendroglial tumors were analyzed. RESULTS: For each histopathologic diagnosis, the number of cases and positive rate of c-Met expression are as follows: oligodendroglioma, IDH-mutant, and 1p19q codeletion (OD): 16 cases, 6.3%; anaplastic oligodendroglioma, IDH-mutant, and 1p19q codeletion (AO): 11 cases, 36.4%; diffuse astrocytoma (DA), IDH-mutant: 21 cases, 28.6%; anaplastic astrocytoma (AA), IDH- mutant: 15 cases, 20%; glioblastoma, IDH-mutant: 2, 100%, DA, IDH-wildtype: 9 cases, 33.3%; AA, IDH-wildtype: 20 cases, 30.0%; and glioblastoma, IDH-wildtype: 59 cases, 52.5%. c-Met expression was correlated with progression-free survival in oligodendroglial tumors and glioblastoma, IDH-wildtype. Furthermore, it was correlated with overall survival in AO, oligodendroglial tumors, DA, IDH-mutant, DA, IDH-wildtype, and glioblastoma, IDH-wildtype, and tend to be correlated with overall survival in IDH-mutant lower-grade astrocytic tumors. CONCLUSIONS: c-Met expression was revealed to be a useful marker for prognosis prediction in IDH-mutant lower-grade gliomas and glioblastoma, IDH-wildtype, representing a new independent prognostic marker that can be easily measured.
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Pathology international 69(6) 372-377 2019年6月 査読有りGlioneuronal tumor (GNT) is a rare central nervous system neoplasm composed of glial and neuronal components. Making the specific diagnosis of GNT can be challenging due to histopathological and genetical similarities among some GNTs and low-grade gliomas. We report a case of GNT with rosette-forming glioneuronal tumor, dysembryoplastic neuroepithelial tumor, and pilocytic astrocytoma-like morphology harboring FGFR1 mutation. A 16-year-old female presented with absence seizures. Magnetic resonance imaging revealed a right temporal lobe mass with multinodular enhancement by gadolinium administration. The tumor was mostly composed of oligodendrocyte-like cells (OLCs) with variable perinuclear haloes. Abundant Rosenthal fibers and eosinophilic granular bodies were identified. Neither mitotic figures nor areas of necrosis were seen. Focal neurocytic rosette features, involving ring-like arrays of OLCs around eosinophilic cores, were observed. Direct sequencing showed a missense mutation in FGFR1 K656E, whereas FGFR1 N546K, PIK3CA, and BRAF V600E were intact. KIAA1549-BRAF fusion was not detected by fluorescence in situ hybridization analysis.
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Neuro-oncology 21(3) 348-359 2019年2月19日 査読有りBACKGROUND: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. METHODS: We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n = 58) or the placebo (n = 30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. RESULTS: Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 30 placebo patients were SART2-93 peptide selection (n = 13 vs 8, hazard ratio [HR]: 15.9), ≥70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SART2-93 selection plus one of these 3 favorable factors (<70 y old, ≤70 kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n = 21) compared with that of the patients without SART2-93 selection (n = 67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T cells, the intermediate levels of chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively. CONCLUSION: This phase III trial met neither the primary nor secondary endpoints.
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World neurosurgery 122 e20-e31-e31 2019年2月 査読有りBACKGROUND: Protecting the venous drainage route during surgery in cases of petroclival meningioma (PCM) is important. Identifying venous congestion preoperatively can be valuable in reducing the risks associated with venous congestion during surgery. In this study, we examined the utility of susceptibility-weighted imaging (SWI) in identifying the presence of venous congestion in PCM cases preoperatively and identified the factors associated with it. METHODS: We retrospectively examined 24 patients who had undergone surgery for primary PCM. The areas of the basal and internal cerebral veins on the affected and unaffected sides, obtained using SWI, were compared to identify venous congestion. We further examined the association between multiple candidate factors that are thought to be related to venous congestion and venous congestion using statistical analyses. RESULTS: SWI could successfully identify venous congestion in 11 of 24 PCM cases. Among the 12 factors examined, those associated with venous congestion were an extension of the tumor, over the midline or upward, which is known to disturb the venous flow at the brainstem surface; anastomosis of the superficial cerebral vein (i.e., bypass route for venous congestion); and a high ABC Surgical Risk Scale score, an indicator of postoperative neurologic deterioration. CONCLUSIONS: We showed that SWI is useful for evaluating venous congestion in PCM cases preoperatively and for identifying factors reflecting the risk of venous congestion. Taken together, our findings provide a multimodal strategy for the preoperative prediction of venous congestion, which could facilitate the treatment of PCM.
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World Neurosurgery 130 e26-e46 2019年Background: The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients. Methods: Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients. Results: Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P < 0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at >7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P < 0.001), and incidence of acute subdural hematoma (OR, 1.89; P < 0.001) were associated with in-hospital mortality in elderly patients with TBI. Conclusions: Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.
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Brain Pathology 2019年
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Brain Pathology 29 174-175 2019年
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Acta neuropathologica communications 6(1) 134-134 2018年12月4日 査読有りExtensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.
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Medical molecular morphology 51(4) 194-198 2018年12月 査読有りTo become immortalized, cells need to maintain the telomere length via the activation of telomerase or alternative lengthening of telomere. Mutations in IDH1/2 are strongly associated with the early stage of gliomagenesis. Previous work has shown that the accumulation of 2-HG, which is induced by mutant IDH1/2, inhibits α-KG-dependent deoxygenase and leads to genome-wide histone and DNA methylation alterations. These alterations are believed to contribute to tumorigenesis. H-Ras can transform human astrocytes with the inactivation of p53/pRb and expression of hTERT however, mutant IDH1 can also transform cells. Moreover, mutant IDH1 can drive the immortalization and transformation of p53-/pRb-deficient astrocytes by reactivating telomerase and stabilizing telomeres in combination with increased histone lysine methylation and c-Myc/Max binding at the TERT promoter. It remains unclear whether mutant IDH1/2 acts only as the initial driver of gliomagenesis or it maintains transformed cells. Clinical studies are being performed to assess the use of mutant IDH1/2 inhibitors for treating gliomas.
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Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27(11) 3148-3154 2018年11月 査読有りBACKGROUND: Cardiac wall motion abnormality (WMA) is a common complication in patients with subarachnoid hemorrhage (SAH) and is one determinant of their prognosis. The aim of this study was to examine whether the electrocardiography (ECG) findings at admission could predict WMA commonly observed after SAH. MATERIALS AND METHODS: We studied 161 SAH patients with SAH who were hospitalized in our institution between April 2007 and November 2010. We performed bedside 2-dimensional transthoracic echocardiography and 12-lead surface ECG within 24hours of SAH onset. Each of the following ECG changes was scored as having 1 point: ST elevation, ST depression and T wave inversion. We summed up the points in every patient and compared with WMA evaluated by echocardiography. RESULTS: The study subjects were classified into 2 groups based on the presence of WMA. Multivariate analysis revealed that ST elevation, ST depression and T wave inversion were strong independent predictors of WMA. Receiver operating characteristic curve determined that the threshold value to predict WMA was 4 points (sensitivity 86.5%, specificity 83.1%, AUC 0.94, P < .0001). CONCLUSIONS: In conclusion, a novel ECG score may well predict WMA after SAH which may associate with an increased risk of mortality.
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Journal of atherosclerosis and thrombosis 25(10) 1022-1031 2018年10月1日 査読有りAIMS: Coronary artery atherosclerosis in patients needing carotid revascularization has not been fully clarified. The aim of this study was to evaluate the stenotic severity and plaque characteristics of coronary arteries by coronary computed tomography angiography (CTA) in patients scheduled for carotid-artery stenting (CAS) or carotid endarterectomy (CEA). METHODS: We performed coronary CTA after carotid ultrasound (US) in 164 patients (81.7% male, aged 68.1± 12.2 years) from 2014 to 2016. Of all, 70 were scheduled for CAS or CEA (CAS/CEA group) and 94 were not (non-CAS/CEA group). Carotid US and coronary CTA were compared for the evaluation of stenotic severity and plaque characteristics of each vessel between CAS/CEA and non-CAS/CEA groups. RESULTS: Between the two groups, there were significant differences in the presence of significant stenosis (SS: ≥70% stenosis of coronary artery) (55.7% vs. 39.4%, P=0.038), triple-vessel disease (TVD)/left main trunk (LMT) (SS in each of three epicardial vessels and/or LMT) (24.3% vs. 7.5%, P= 0.0025), and high-risk plaque (HRP: positive remodeling and/or low attenuation) (55.7% vs. 24.5%, P＜0.0001). CAS/CEA was independently associated with TVD/LMT (OR=2.30, 95%CI: 1.14-8.59, P=0.026) and HRP (OR=3.17, 95%CI: 1.57-6.54, P=0.0012) in multivariable logistic regression analysis. Similarly, vulnerable plaque (78.6% vs. 2.1%, P＜0.0001) as well as severe stenosis of carotid artery (98.6% vs. 0%, P＜0.0001) was seen more often in CAS/CEA than in non-CAS/CEA group. CONCLUSIONS: The prevalence of TVD/LMT and HRP determined by coronary CTA is higher in patients needing CAS/CEA than in those without. Management of systemic atherosclerosis is required in the perioperative period of CAS/CEA.
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Asian journal of neurosurgery 13(4) 995-1000 2018年10月 査読有り
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Brain Tumor Pathology 35(Suppl.) 169-169 2018年9月
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World neurosurgery 116 e611-e623-e623 2018年8月 査読有りBackground: The anterior transpetrosal (ATP) approach is the most appropriate approach for petroclival meningiomas (PCMs), which are typically located from the dorsum sellae to the upper border of the internal auditory meatus (IAM). Although neurosurgeons can resect over this area if the tumor is detached from the dura, tumors within the indication area for PCMs are not appropriate for the ATP approach, because it can be difficult to evaluate whether the tumor is attached to or only touching the dura. In this study, we investigated the tumor extension area based on an evaluation of the feeding artery to achieve a more accurate assessment of the dural attachment area. Methods: Using various angiography techniques, we studied 51 feeding arteries from 24 patients who had undergone surgical treatment of primary petroapex meningiomas and PCMs via the ATP approach. We measured the lower and posterior extension distances, the extension rate of the cavernous sinus and Meckel's cave, and the midline extension rate of the tumors. Results: The ascending pharyngeal artery (AphA) was the predominant feeding artery for tumors with lower extension. We determined that tumors extending over the lower border of IAM in cases in which the feeding artery was not the AphA can be resected using the ATP approach. Conclusions: This study shows an association between the predominant feeding artery and tumor extension area and demonstrates that an evaluation of the dural attachment area based on the feeding artery can aid selection of the appropriate surgical approach.
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Asian journal of neurosurgery 13(3) 619-625 2018年7月 査読有り
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Asian journal of neurosurgery 13(3) 779-781 2018年7月 査読有り
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Neurology 90(13) e1143-e1149 2018年5月 査読有り
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Carotid stenting for unilateral stenosis can increase contralateral hemispheric cerebral blood flow.Journal of neurointerventional surgery 10(4) 351-354 2018年4月1日 査読有りBackground The revascularization of carotid stenosis can increase ipsilateral cerebral blood flow (CBF). Occasionally, elevated CBF is also evident on the contralateral side, but this phenomenon is poorly understood. Objective To analyze retrospectively the relationship between a contralateral CBF increase and several clinical and radiologic features. Materials and methods We retrospectively analyzed 40 patients with unilateral cervical carotid stenosis treated by carotid artery stenting (CAS). Using 123 I-iodamphetamine single-photon emission computed tomography (SPECT) we compared pre-and postoperative hemispheric CBF on both sides. We investigated the influence of the following five factors on the increase of the contralateral hemispheric CBF: stenosis grade (≥50% or < 50%, according to the North American Symptomatic Carotid Endarterectomy Trial criteria) age the presence of anterior and posterior communicating arteries postoperative hyperperfusion on the stenotic side and the presence of cerebral steal phenomenon during preoperative acetazolamide-challenge SPECT. Results Following unilateral CAS, mean hemispheric CBF increased significantly on both sides: from 33.4±5.6 (mean ± SD) to 38.7±7.8 mL/min on the operated side (paired t test, p< 0.001) and f35.4±5.4 to 39.2±7.2 mL/min on the contralateral side (p< 0.001). In a general linear model, stenosis grade (≥50%) alone was significantly correlated with the increase of the CBF on the contralateral side (p=0.03). Conclusion Revascularization by CAS for unilateral carotid stenosis can increase hemispheric CBF on both sides. Increase of the contralateral CBF is correlated with stenosis grade (≥50%).
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Journal of Neurosurgery-spine 28(3) 262-267 2018年3月1日 査読有りChiari malformation type I (CM-I) is typically treated with foramen magnum decompression. However, a recent study proposed a new technique for patients with CM-I, wherein only short atlantoaxial joint fusion and distraction is applied. Posterior fusion with or without atlantoaxial distraction is a potential option for patients with CM-I associated with basilar invagination or complex anomalous bony craniovertebral junction pathology, since this procedure allows clinicians to avoid using the technically demanding transoral approach in which some or all of the odontoid tip is invisible. Distraction of the atlantoaxial joint reduces ventral cervicomedullary compression, leading to neurological improvement. Here, the authors report the case of a 50-year-old woman with CM-I plus basilar invagination whose condition immediately improved but then gradually deteriorated following atlantoaxial joint distraction and fusion. Therefore, the authors performed endonasal/transoral odontoidectomy, which resulted in prolonged neurological recovery. Short atlantoaxial fusion with distraction is a smart and ideal surgical planning concept that can result in significant neurological improvement. However, this case suggests that anterior odontoidectomy is still an essential element of the intervention strategy for patients with CM-I with complex craniovertebral junction pathology.
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Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 17(1) 42-49 2018年1月10日 査読有りPurpose: We evaluated the diagnostic performance of histogram analysis of data from a combination of dynamic susceptibility contrast (DSC)-MRI and dynamic contrast-enhanced (DCE)-MRI for quantitative differentiation between central nervous system lymphoma (CNSL) and high-grade glioma (HGG), with the aim of identifying useful perfusion parameters as objective radiological markers for differentiating between them. Methods: Eight lesions with CNSLs and 15 with HGGs who underwent MRI examination, including DCE and DSC-MRI, were enrolled in our retrospective study. DSC-MRI provides a corrected cerebral blood volume (cCBV), and DCE-MRI provides a volume transfer coefficient (Ktrans) for transfer from plasma to the extravascular extracellular space. Ktransand cCBV were measured from a round region-of-interest in the slice of maximum size on the contrast-enhanced lesion. The differences in t values between CNSL and HGG for determining the most appropriate percentile of Ktransand cCBV were investigated. The differences in Ktrans, cCBV, and Ktrans/cCBV between CNSL and HGG were investigated using histogram analysis. Receiver operating characteristic (ROC) analysis of Ktrans, cCBV, and Ktrans/cCBV ratio was performed. Results: The 30th percentile (C30) in Ktransand 80th percentile (C80) in cCBV were the most appropriate percentiles for distinguishing between CNSL and HGG from the differences in t values. CNSL showed significantly lower C80 cCBV, significantly higher C30 Ktrans, and significantly higher C30 Ktrans/C80 cCBV than those of HGG. In ROC analysis, C30 Ktrans/C80 cCBV had the best discriminative value for differentiating between CNSL and HGG as compared to C30 Ktransor C80 cCBV. Conclusion: The combination of Ktransby DCE-MRI and cCBV by DSC-MRI was found to reveal the characteristics of vascularity and permeability of a lesion more precisely than either Ktransor cCBV alone. Histogram analysis of these vascular microenvironments enabled quantitative differentiation between CNSL and HGG.
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Neurology and Clinical Neuroscience 2018年
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Journal of Neurosurgery-spine 2018年
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Cancer Science 109 1126-1126 2018年1月 査読有り
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World neurosurgery 109 197-201 2018年1月1日 査読有りBackground Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel-induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). Case Description A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel-induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patient's symptoms improved after the insertion of a ventriculoperitoneal shunt. Conclusions In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis.
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Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 47 228-233 2018年1月1日 査読有りBrainstem glioma is impossible to resect completely, and patients with this type of glioma show a poor prognosis. Therefore, a more effective adjuvant therapy is required to prolong survival. Bevacizumab is an endothelial growth factor monoclonal antibody with strong anti-vascular effects, which may suppress tumor progression. We performed a retrospective study of data from 6 patients with brainstem glioma showing malignant features who were treated with bevacizumab. Tumor-associated lesions, as evaluated by T2 weighted or fluid-attenuated inversion-recovery magnetic resonance imaging, were reduced in all patients, although the timing of the start of bevacizumab administration and pretreatment were not uniform. Clinical symptoms improved in 4 patients and progression was inhibited in 2 patients. The Karnofsky performance status improved from 56.7 to 71.7 on average. The median reduction ratio of tumor-associated lesions was 76.3%, but tumor suppression did not last in any of the cases. Furthermore, 5 patients died of tumor progression, and 1 patient died of a complication of necrotizing colitis. The median progression-free survival after bevacizumab administration was 7 months. The median overall survival after diagnosis was 16.5 months. Bevacizumab might be a potential therapeutic option for progressive brainstem gliomas with malignant features.
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Asian journal of neurosurgery 13(1) 119-122 2018年1月 査読有り
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神経外傷 40(2) 117-120 2017年12月症例は16歳男子で、直線道路でヘルメットを装着せず、患者が運転するバイクが軽自動車に70km/hで追突した。10分後、救急隊が到着し、患者は臥位で顔面と右膝に挫創を認め、左頸部挫創から大量出血していた。頸部を圧迫止血した。バイタルサインはJCS1-2、脈拍139回/分、左下腿測定で血圧93(拡張期は測定不能)mmHgであった。蘇生処置を緊急的に要請し、受傷23分後に現発し、33分後に病着した。GCSE4V4M5、脈拍108回/分、血圧75/35mmHgとショック状態で、左頸部に10cmの挫創を認めた。挫創から圧迫止血を介助すると動脈性出血が噴出した。他に顔面挫創、右膝挫創、右足底部挫創を認めFASTは1回目陰性であった。救急車内で急速静注で細胞外輸液を行っていた。脳神経外科の医師により縫合処置を行った。縫合処置後、脳血管撮影(DSA)を行い縫合部の狭窄、再出血がないことを確認した。第7病日に人工呼吸器を離脱し、第8病日に再度DSAを行い、総頸動脈の狭窄、外傷性動脈瘤等がないことを再度確認し、第15病日に自宅退院した。
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Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 33(12) 2077-2078 2017年12月 査読有り
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Oncotarget 8(49) 84729-84742 2017年10月17日 査読有りMost IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan (R) arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.
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Neurologia medico-chirurgica 57(10) 505-512 2017年10月15日 査読有りThe evaluation of venous drainage patterns prior to surgery for skull base meningioma is important owing to their deep location and the vulnerability of surrounding vascular structures. In recent years, the microsurgical skull base approach has matured as a surgical technique, making it an important option for reducing complications related to skull base meningioma surgery. In addition, knowledge of the venous anatomy can prevent venous drainage route disturbance and potentially life-threatening complications. Hence, this topic review aimed to provide an overview of normal venous anatomy as it relates to the microsurgical skull base approach, discuss known changes in venous drainage routes that are associated with the progression of skull base meningioma and the selection of an appropriate operative approach with the highest likelihood of preserving venous drainage structures.
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Journal of neurosurgical sciences 61(5) 495-503 2017年10月 査読有りBACKGROUND: Pregabalin (PGB), a drug used for treating neuropathic pain, has immune-modulating property that may have therapeutic implications. Suppression of microglial activation and improvement in functional recovery was observed in experimental spinal cord injury after PGB administration. An experimental study was conducted to evaluate whether PGB could afford neuroprotection in a rat model of intracisternal facial nerve avulsion. METHODS: Twenty-eight male Wistar rats (250-300 g) were dichotomized into two groups: a PGB group (N.=14) and a control group (N.=14). The PGB group received a total of 4 intraperitoneal PGB injections (30 mg/kg, 15 minutes preoperatively and 4, 24, and 48 hours postoperatively), and the control group underwent intraperitoneal saline injection. Intracisternal facial nerve avulsion was created by tangential pull-out of the nerve surgically exposed at the stylomastoid foramen. In both groups, the brainstem containing the facial motor nuclei neurons was thin-sliced and stained with cresyl violet, and the number of viable neurons in the facial motor nuclei on days 14 and 28 was counted under microscope. RESULTS: The total viable neuron count was significantly greater in the PGB group than in the Control group both on day 14 (271.4 +/- 14.9 vs. 196.2 +/- 22.2, P<0.01) and day 28 (160.2 +/- 21.6 vs. 102.6 +/- 13.4, P<0.01). Furthermore, CD11b/c immunostaining on days 3 and 8 showed that CD11b/c-positive cells, suggestive of activated microglia, were observed only in the control group. CONCLUSIONS: Better neuronal survival by PGB administration may be beneficial and clinically relevant when surgical reconstruction of the facial nerve, such as hypoglossal-facial nerve anastomosis, is considered.
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Asian journal of neurosurgery 12(4) 644-647 2017年10月 査読有り
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Journal of Clinical Oncology 35(15_suppl) 2000-2000 2017年5月20日 査読有り2000 Background: To establish whether personalized peptide vaccination (PPV) is clinically beneficial for human leukocyte antigen (HLA)-A24-positive glioblastoma multiforme (GBM) patients refractory to temozolomide (TMZ)-based therapy. Methods: From January 2012 to March 2016, 88 HLA-A24-positive GBM patients refractory to TMZ-based therapy from 20 Japanese hospitals were randomly assigned to receive PPV treatment (n = 58) or best supportive care (BSC) (n= 30) at a 2 to 1 ratio. Four peptides chosen from 12 peptide candidates based on pre-vaccination IgG levels specific to each peptide or 4 corresponding placebos were injected subcutaneously once weekly for 12 times at the first course followed by biweekly vaccinations until disease progression. The primary endpoint was overall survival (OS). Results: The primary endpoint was not met in this clinical trial. Unfavorable prognostic factors were performance status (PS) 3, higher plasma levels of pre-vaccination granulocyte macrophage-colony stimulating factor (GM-CFS), and PPV containing SART2-derived peptides. Therefore, 78 patients with PS of 0 to 2 (50 with PPV and 28 with BSC) were provided for the subgroup analysis. Among them, the median OS of 39 PPV patients (10.4 months, 95% CI, 7.8-12.0 months) who had either lower levels of GM-CSF ( < 0.9 pg/mL) or 4 peptide vaccinations that did not include SART2-derived peptides was significantly (p = 0.03) longer than that of the corresponding 19 BSC patients (6.8, 4.6-12.7). In contrast, the median OS of 10 PPV patients (4.1, 1.1-8.3) who had both higher levels of GM-CSF ( > 0.9 pg/mL) and 4 peptide vaccinations containing SART2-derived peptides was significantly (p = 0.01) shorter than that of the corresponding 9 BSC patients (not reached, 1.6-not reached). A single grade 3 adverse event was the only PPV-related adverse event of grade > 3 in this study. Conclusions: PPV monotherapy could be a new treatment modality for HLA-A24-positive GBM patients refractory to TMZ-based therapy, since this approach showed clinical benefit and safety under precision medicine-based pre-vaccination selection of appropriate patients. Clinical trial information: UMIN000006970.
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Journal of neuro-oncology 132(1) 119-126 2017年3月 査読有りAlthough 1p19q codeleted gliomas are the most favorable molecular subgroup of lower-grade gliomas, there are cases with early recurrence or short survival. The objective of this study was to elucidate molecu-lar- genetic and clinicopathological prognostic factors in patients with gliomas showing total 1p19q loss. The study included 57 consecutive patients with codeleted gliomas who were operated at Keio University Hospital between 1990 and 2010. These patients were assessed for chromosomal copy number aberrations, promoter methylation status of the O6-methylguanine-DNA methyltransferase gene (MGMT), and demographic and clinicopathological prog-nostic factors in diffuse gliomas. No significant difference was observed in the overall survival (OS) of the patients with respect to age (>= 40 years vs. < 40 years), degree of resection, maximum tumor diameter (>= 5 cm vs. < 5 cm), histological subtype, and MGMT promoter methylation sta-tus. Gain of chromosome 19p and grade III histology were associated with shorter OS (P = 0.019, 0.061, respectively). Gain of 19p and histological grade III might be negative prognostic factors for the patients with gliomas showing total 1p19q loss. Further investigation is warranted to con-firm these notions.
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Acta neuropathologica 133(3) 445-462 2017年3月 査読有りIntracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.
MISC
186書籍等出版物
14講演・口頭発表等
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The 3rd Symposium of WFNOS 2021 2019年7月28日 招待有り
所属学協会
6共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2023年3月
教育内容・方法の工夫（授業評価等を含む）
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件名臨床医学への興味を喚起する教育を試みる開始年月日2010終了年月日2012概要Ｍ3「神経系」講義において、手術ビデオの供覧など臨床医学に対する興味を促進した。
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件名臨床医学への興味を喚起する教育を試みる開始年月日2010終了年月日2012概要M5臨床実習においてカルテ記載を促進し、疾患の理解を促した。