Toshihiro Kumabe

Kitasato University, Edo, Tōkyō, Japan

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Publications (247)585.42 Total impact

  • R. Saito · Y. Sonoda · M. Kanamori · T. Kawaguchi · T. Kumabe · T. Tominaga ·

    Neuro-Oncology 11/2015; 17(suppl 5):v186-v187. DOI:10.1093/neuonc/nov229.04 · 5.56 Impact Factor

  • Neuro-Oncology 11/2015; 17(suppl 5):v6-v6. DOI:10.1093/neuonc/nov206.23 · 5.56 Impact Factor
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    ABSTRACT: Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution.
    Neurologia medico-chirurgica 10/2015; DOI:10.2176/ · 0.72 Impact Factor
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    ABSTRACT: Background and purpose: Radiation-induced cerebral cavernous malformation reflects post-irradiation impairment of cerebral microcirculation. Our purpose was to determine effects of radiation field size and dose on the extent of developing cavernous malformations in long-term survivors of intracranial germ cell tumors (GCTs). Methods: The study involved 34 patients with a history of intracranial GCTs treated with either whole-brain or reduced-field irradiation and undergoing magnetic resonance (MR) imaging with a mean follow-up of 18.5years. The number of cavernous malformations on T2*-weighted MR images between whole-brain and reduced-field irradiation groups as well as between high- (50.2Gy) and low-dose (24.4Gy) fields were compared. Results: A total of 235 cavernous malformation lesions were observed in 32 of 34 patients (94.1%). The mean number of lesions was 2.3 times as high in the whole-brain group as in the reduced-field group (P=0.00296). The number of lesions in high-dose fields was significantly larger than in low-dose (P<0.000001) or untreated fields (P<0.001). Conclusion: Radiation field size and dose were positively associated with the number of cavernous malformations developed. Cavernous malformations detected on MR imaging can be used as a surrogate marker for microvascular injury following intracranial irradiation in long-term cancer survivors.
    Radiotherapy and Oncology 09/2015; DOI:10.1016/j.radonc.2015.09.017 · 4.36 Impact Factor
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    ABSTRACT: We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome.
    Brain & development 09/2015; DOI:10.1016/j.braindev.2015.07.005 · 1.88 Impact Factor
  • Satoru Shimizu · Takahiro Mochizuki · Shigeyuki Osawa · Toshihiro Kumabe ·
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    ABSTRACT: After the drainage of chronic subdural hematomas (CSDHs), residual isolated deep-seated hematomas (IDHs) may recur. We introduce intraoperative ultrasonography to detect and remove such IDHs. Intraoperative ultrasonography is performed with fine transducers introduced via burr holes. Images obtained before dural opening show the CSDHs, hyper- and/or hypoechoic content, and mono- or multilayers. Images are also acquired after irrigation of the hematoma under the dura. Floating hyperechoic spots (cavitations) on the brain cortex created by irrigation confirm the release of all hematoma layers; areas without spots represent IDHs. Their overlying thin membranes are fenestrated with a dural hook for irrigation. Ultrasonographs were evaluated in 43 CSDHs (37 patients); 9 (21%) required IDH fenestration. On computed tomography scans, 17 were homogeneous-, 6 were laminar-, 16 were separated-, and 4 were trabecular type lesions. Of these, 2 (11.8%), 3 (50%), 4 (25%), and 0, respectively, manifested IDHs requiring fenestration. There were no technique-related complications. Patients subjected to IDH fenestration had lower recurrence rates (11.1% vs. 50%, p = 0.095) and required significantly less time for brain re-expansion (mean 3.78 ± 1.62 vs. 18 ± 5.54 weeks, p = 0.0009) than did 6 patients whose IDHs remained after 48 conventional irrigation and drainage procedures. Intraoperative ultrasonography in patients with CSDHs facilitates the safe release of hidden IDHs. It can be expected to reduce the risk of postoperative hematoma recurrence and to shorten the brain re-expansion time.
    Neurologia medico-chirurgica 09/2015; 55(9). DOI:10.2176/ · 0.72 Impact Factor
  • Mari Kusumi · Hidehiro Oka · Hamidreza Aliabadi · Sumito Sato · Toshihiro Kumabe ·

    World Neurosurgery 09/2015; DOI:10.1016/j.wneu.2015.08.048 · 2.88 Impact Factor
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    ABSTRACT: i>Objective :When employing the lateral suboccipital approach, the thin dura shrinks due to the drying effect of illumination and air exposure, and dural substitutes are often needed for closure. We developed a new technique involving dural moisturizing with fibrin glue coating that facilitates primary dural closure. Patients and Methods :We used this technique in 12 adults who underwent the lateral suboccipital approach for 5 hemifacial spasms, 3 trigeminal neuralgias, 2 cerebellopontine meningiomas, 1 vestibular schwannoma, and 1 vertebral artery aneurysm. Fibrin glue was sprayed on the outer surface before opening the dura, and additionally sprayed on the inner surface of the reflected dural flap after opening the dura. After the intradural procedures the dura was closed with the usual knotted sutures. Results :Dural closure was performed 65-340 minutes(mean:161.9 minutes)post-durotomy. This technique resulted in primary dural closure with a sufficient area of preserved dura in all but one patient. In this patient, the dura shrank due to coagulation of the dural attachment to the meningioma for which a small autologous substitute was required. There were no procedure-related complications such as cerebrospinal fluid leakage and meningitis. Conclusions :Dural moisturizing with fibrin glue coating is simple, protects the dura from drying and shrinkage, and facilitates primary dural closure in patients undergoing the lateral suboccipital approach.
    No shinkei geka. Neurological surgery 08/2015; 43(8):709-12. DOI:10.11477/mf.1436203107 · 0.13 Impact Factor
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    ABSTRACT: As cerebrovascular anastomosis is performed in moist conditions that may impede precise manipulations, surgeons must undergo extensive preoperative training. We developed a simple moist-condition training method. It involves placing a free-floating inner platform hosting an artery from a chicken wing in an outer container filled with tap water to just below the specimen. Trainees performed anastomosis under magnification. Training sessions mimicked difficulties encountered during operations such as poor visibility of the lumen and problems handling the sutures. A retrospective comparison of 100 wet- and 100 dry-condition training sessions for end-to-side anastomoses with 8 stitches showed that under moist condition the time required for the entire procedure was significantly longer (17.8 ± 2.1 vs. 15.3 ± 2.1 min, p < 0.01) and the incidence of wrong stitching was greater (0.38 vs. 0%, p = 0.04). In 8 cases after introducing moist-condition training, the time required in superficial temporal artery to middle cerebral artery bypass surgery was significantly shorter than 8 cases before introducing the training (32.3 ± 5.6 min vs. 48.3 ± 15.9 min, p = 0.01). Incidence of wrong stitches was less in cases after introducing moist-condition training (2.7 vs. 7.4%, p = 0.10). Those indicate that moist-condition training is a useful and practical step and a bridge between training for basic manipulations under dry conditions and actual surgery.
    Neurologia medico-chirurgica 07/2015; 55(8). DOI:10.2176/ · 0.72 Impact Factor
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    ABSTRACT: Pseudopalisades (Ps) around necrotic foci are severely hypoxic and overexpress hypoxia-inducible factor (HIF) in glioblastoma (GBM). Hypoxic regions have been proposed as one of several distinct niches for cancer stem cells (CSCs) in GBM, but little is known about the association between Ps features and CSC properties. Herein, we focused on the biological role of Ps lesions. In clinical cases of GBM, expression of hypoxia-related molecules including HIF-1α, Glut-1, p27(Kip1), and pAkt was significantly increased in perinecrotic Ps lesions compared with nonnecrotic areas and perinecrotic lesions lacking Ps features. Significantly higher expression levels of several CSC-related markers, including CD133, Sox2, CD44s, and aldehyde dehydrogenase (ALDH) 1, were also observed in Ps lesions, which were positively correlated with expression of hypoxia-related molecules and pAkt. Ps lesions also showed increased number of apoptotic cells and decreased bcl-2 and survivin expression compared with the surrounding tissue. Short-term exposure of astrocytoma cell lines to cobalt chloride, which is known to mimic the effect of hypoxia, caused an increase in expression of both hypoxia- and CSC-related markers, in line with increases in the ALDH(high) cell population and number of spheroids. Inhibition of endogenous Akt by LY294002 resulted in decreased expression of Sox2, ALDH1, and CD133, leading to enhancement of cobalt chloride-mediated apoptotic events due to altered ratio of bcl-2 to bax expression. These findings suggest that Ps lesions within GBM may serve as a specialized hypoxic niche, in which the HIF-1α/pAkt axis is activated, in response to severe hypoxia. Copyright © 2015. Published by Elsevier Inc.
    Human pathology 06/2015; 46(10). DOI:10.1016/j.humpath.2015.06.008 · 2.77 Impact Factor

  • Journal of Neurological Surgery, Part B: Skull Base 06/2015; DOI:10.1055/s-0035-1554903 · 0.72 Impact Factor
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    ABSTRACT: Human chorionic gonadotropin (hCG) production has been utilized as a diagnostic marker for germinoma with syncytiotrophoblastic giant cells (STGC) and choriocarcinoma. Elevated hCG in germinoma is considered to predict less favorable prognosis, and an intensive treatment strategy may accordingly be applied. However, there is some evidence that any germinoma may produce hCG to varying extent. We investigated mRNA expression of the hCG β subunit (hCGβ) using real time quantitative polymerase chain reaction in 94 germ cell tumors (GCTs). Most (93.3 %) GCTs showed higher expression levels compared with that of normal brain tissue (1.09 × 10(0)-1.40 × 10(5) fold). The expression was the highest in GCTs which harbor choriocarcinoma or STGC components. The expression level of hCGβ in germinoma was highly variable (1.09 × 10(0)-5.88 × 10(4) fold) in linear but not bimodal distribution. hCG concentrations in serum and CSF correlated with gene expression, especially when GCTs with single histological component were analyzed separately. The expression was not significantly associated with recurrence in pure germinoma. These results suggest that the serum/CSF hCG levels may need to be interpreted with caution as most GCTs appear to have the capacity of producing hCG irrespective of their histology. The clinical significance of ubiquitous hCG expression in GCTs needs further investigation.
    Journal of Neuro-Oncology 05/2015; 124(1). DOI:10.1007/s11060-015-1809-y · 3.07 Impact Factor
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    ABSTRACT: Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2-4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5-11 years were I. Sato et al. 452 provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12-18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety , Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.
    Open Journal of Nursing 04/2015; 5(05):451-464. DOI:10.4236/ojn.2015.55048
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    ABSTRACT: Moyamoya disease more commonly occurs in young people and women, so patients with this disease may experience pregnancy and delivery. Cesarean section (CS) is often chosen as the mode of delivery for these patients in Japan. No appropriate mode of delivery has yet been established for pregnant women with moyamoya disease in terms of stroke prevention. We have used vaginal delivery under epidural analgesia (EA) in such patients unless CS has been indicated for the maternal or fetal reasons. This study retrospectively analyzed our patients with moyamoya disease who gave birth to confirm the safety of vaginal delivery under EA. Twelve consecutive patients diagnosed with moyamoya disease had 14 deliveries at our hospital between September 2004 and January 2013. The incidences of intrapartum stroke were compared between cases of vaginal delivery under EA and CS cases. Ten vaginal deliveries under EA and 4 elective CSs were performed. No intrapartum stroke was observed during either vaginal delivery under EA or CS. Among the patients who underwent vaginal delivery under EA, 1 parturient who experienced 2 deliveries suffered transient ischemic attack during both postpartum periods. All 14 infants were healthy without sequelae. Vaginal delivery under EA is an option for patients with moyamoya disease, provided that close cooperation with neurosurgeons, obstetricians, and anesthesiologists is assured. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 03/2015; 24(5). DOI:10.1016/j.jstrokecerebrovasdis.2014.11.030 · 1.67 Impact Factor
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    ABSTRACT: This retrospective study was aimed to compare the perioperative complications for internal carotid artery stenosis (ICS) in a Japanese single institute between the use of carotid artery stenting (CAS) alone or the use of an appropriate individualized treatment method allowing either carotid endarterectomy (CEA) or CAS based on patient risk factors. Based on the policy at our hospital, only CAS was performed on patients (n = 33) between January 2005 and November 2009. From December 2009 to December 2012, either CEA or CAS (tailored treatment) was selected for patients (n = 61) based on individual patient risk factors. CEA was considered the first-line treatment in all cases. In high-risk CEA cases, CAS was performed instead (n = 11), whereas in low-risk CEA cases, CEA was performed (n = 19). Further, in moderate-risk CEA cases based on own criteria, CAS was considered first, whereas for high-risk CAS cases, CEA was performed (n = 17). For low-risk CAS cases, CAS was performed (n = 9). Perioperative clinical complications (any stroke, myocardial infarction, or death within 30 days) were compared between both periods. Significantly reduced perioperative complications were observed during the tailored period (4/61 sites, 6.6%) as compared with the CAS period (8/33 sites, 24.2%) [Fisher's exact test p = 0.022; odds ratio, 4.56 (CAS/tailored); 95% confidence interval, 1.26-16.5]. Selecting an appropriate individualized treatment method according to patient risk factors, as opposed to adhering to a single treatment approach such as CAS, may contribute to improved overall outcomes in patients with ICS.
    Neurologia medico-chirurgica 02/2015; 55(2). DOI:10.2176/nmc.oa.2014-0049 · 0.72 Impact Factor
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    ABSTRACT: Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy. Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O2). OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10. Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment.
    Molecular Cancer 02/2015; 14(1):41. DOI:10.1186/s12943-015-0307-3 · 4.26 Impact Factor
  • Kimitoshi Sato · Toshihiro Kumabe ·
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    ABSTRACT: Transdural anastomosis (TA) from the middle meningeal arteries (MMAs) to the brain is important in maintaining cerebral blood flow in patients with Moyamoya disease. A 16-year-old adolescent girl presented with a transient ischemic attack. Preoperative cerebral angiography revealed TA from the MMA. During surgery, the MMA was exposed on the dural surface directly under the burr hole. Measurement of flow velocity in the MMA with an ultrasonic blood flowmeter revealed increased diastolic flow velocity. As the MMA was assumed to contribute to TA, a new burr hole was made to preserve the MMA, and a bone flap was prepared. Direct and indirect bypass surgeries were performed. Electrocoagulation was not applied to the MMA associated with TA, but the artery was compressed with gelfoam containing fibrin glue to achieve hemostasis. Postoperatively, no evidence of cerebral infarction was detected. Determining which of several MMAs exposed in the surgical field is associated with TA can be difficult. However, measurement of flow velocity with an ultrasonic blood flowmeter to confirm increased flow velocity in the diastolic phase is useful for confirming the presence or absence of TA from the extracranial arteries including the MMA.
    01/2015; DOI:10.1515/ins-2015-0011
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    ABSTRACT: This report presents rosette-forming glioneuronal tumor (RGNT) of the tectum in a 24-year-old woman in whom spontaneous disappearance of contrast enhancement (CE) on magnetic resonance (MR) imaging was observed during 9-year follow-up period before therapeutic intervention. MR imaging obtained 9 years ago when she first visited local hospital with headaches showed a mass of the brain stem with CE. Follow-up MR imaging showed disappearance of CE without tumor growth. Nine years later, she was admitted to our hospital with headache and nausea, due to obstructive hydrocephalus. She underwent endoscopic third ventriculostomy (ETV) and tumor biopsy. Histological study revealed RGNT. To our knowledge, this is the first report presenting that the RGNT may show spontaneous disappearance of CE without tumor growth. It is unclear what this phenomenon means, however, knowledge of this phenomenon may be helpful for correct diagnosis and for follow up of RGNT.
    01/2015; 2(2):65-67. DOI:10.2176/
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    ABSTRACT: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0174-y) contains supplementary material, which is available to authorized users.
    12/2014; 2(1):3. DOI:10.1186/s40478-014-0174-y
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    ABSTRACT: The aim of this study was to determine if molecular alterations are associated with tumor location and radiological characteristics in anaplastic gliomas. We performed a retrospective analysis of 122 anaplastic gliomas for molecular alterations (IDH1/2 mutations, TP53 mutations, and 1p19q co-deletion) to compare MRI features (location and image characteristics). We observed that IDH mutation is strongly associated with frontal location (P = 0.001). However, 13 tumors not located in the cerebral cortex were IDH intact tumors (P < 0.0001). While IDH mutation and TP53 mutation are significantly associated with AA (p < 0.0001), IDH mutation and 1p19q co-deletion were significantly associated with AO/AOA (p < 0.0001). No tumors with IDH mutation and 1p19q co-deletion infiltrated the temporal lobe (P = 0.003). The tumors with 1p19q co-deletion and histologically diagnosed as AO/AOA were associated with contrast enhancement on MR images (p = 0.007, p = 0.002, respectively) and those with TP53 mutation had a weak association with sharp tumor borders (p = 0.043). MRI features might be useful to predict molecular profiles in anaplastic gliomas.
    Brain Tumor Pathology 12/2014; 32(2). DOI:10.1007/s10014-014-0211-3 · 1.22 Impact Factor

Publication Stats

3k Citations
585.42 Total Impact Points


  • 2013-2015
    • Kitasato University
      Edo, Tōkyō, Japan
    • University of Toronto
      Toronto, Ontario, Canada
  • 2014
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan
  • 1994-2014
    • Tohoku University
      • Department of Neurosurgery
      Sendai-shi, Miyagi, Japan
  • 2005
    • Sendai City Hospital
      Sendai, Kagoshima, Japan
  • 1999-2005
    • Kohnan Hospital
      Sendai, Kagoshima, Japan