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  • Author or Editor: Masayuki Kanamori x
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Masayuki Kanamori, Toshihiro Kumabe, Mika Watanabe and Teiji Tominaga

✓The authors present the case of a 51-year-old man who presented with an anaplastic astrocytoma and anaplastic oligo-dendroglioma that developed 6 years after subtotal resection of a central neurocytoma in his right lateral ventricle. He had received neither radiation therapy nor chemotherapy after the original resection. On readmission, neuroimaging revealed a mass in the right parietal lobe and a diffuse lesion in the right temporal lobe, insula, and corona radiata. Because both lesions extended to the right lateral ventricle wall, they were regarded as recurrent rather than metachronous tumors. Histological examination revealed anaplastic oligodendroglioma in the parietal lobe and anaplastic astrocytoma in the insula. One year later, the anaplastic astrocytoma was found to have transformed into a glioblastoma multiforme. Fluorescence in situ hybridization analysis and immunohistochemical examinations detected deletions of the 1p36 and 19q13 loci, and nuclear accumulation of TP53 protein in the anaplastic oligodendroglioma but not in the glioblastoma multiforme. These findings suggest that central neurocytoma or progenitor cells have the potential for oligodendrocytic and astrocytic transformation with different genetic aberrations.

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Atsushi Kanoke, Masayuki Kanamori, Toshihiro Kumabe, Ryuta Saito, Mika Watanabe and Teiji Tominaga

This patient presented with a rare case of metachronous, multicentric gliomas first manifesting as headache and nausea in 1983 when he was an 8-year-old boy. Computed tomography revealed a cerebellar tumor and the tumor was subtotally resected. The histological diagnosis was pilocytic astrocytoma, and radiation therapy to the posterior fossa and chemotherapy consisting of nimustine hydrochloride and fluorouracil were performed. In 1989, at age 14 years, the patient presented with local recurrence. He underwent gross-total resection of the tumor, and histological examination revealed that the tumor consisted of classic pilocytic astrocytoma with a biphasic pattern and a small oligodendroglioma-like component. In 2011, at age 36 years, he presented with seizure. Magnetic resonance imaging revealed a mass lesion in the right middle frontal gyrus. Gross-total resection of the tumor was performed, and the histological diagnosis was oligodendroglioma. Genetic analyses revealed amplification of the BRAF gene in both the primary cerebellar pilocytic astrocytoma and the recurrent tumor with biphasic features, as well as a BRAF V600E missense mutation in the oligodendroglioma-like component. On the other hand, the IDH1 R132H mutation, instead of aberrations of the BRAF gene, was identified in the oligodendroglioma arising in the right frontal lobe. Different types of aberrations of the BRAF gene in the classic and oligodendroglioma-like component in the recurrent pilocytic astrocytoma suggest that they had different cell origins or that amplification of BRAF was negatively selected under the de novo BRAF V600E mutation. In addition, the aberration profiles of IDH1 and BRAF suggest that the oligodendroglioma arose independent of cerebellar pilocytic astrocytoma.

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Ryuta Saito, Toshihiro Kumabe, Yukihiko Sonoda, Masayuki Kanamori, Shunji Mugikura, Shoki Takahashi and Teiji Tominaga

Object

The atrium of the lateral ventricle is often affected by tumors, and some patients with these tumors suffer neurological deficits, including hemiparesis after surgery. The authors of this study investigated the possible mechanisms causing the relatively high incidences of ischemic complications associated with surgery approaching the atrium of the lateral ventricle.

Methods

Clinical records and radiological images of 28 patients were retrospectively studied. These patients had their lateral ventricles opened at the atrium during the resection of gliomas as well as other nonbenign brain tumors, and were treated for gliomas at our tertiary referral center in the Tohoku district, Japan, between January 2008 and December 2010.

Results

Routine postoperative diffusion-weighted MR images obtained within 72 hours after surgery detected infarction in the periatrial/periventricular regions in 7 patients, presumably corresponding to the lateral posterior choroidal artery (LPChA) territory. Five of these 7 patients suffered neurological sequelae with varying severities. The choroid plexus at the atrium was coagulated to achieve hemostasis during the surgery in all of these patients. Detailed analysis of microangiograms revealed ventriculofugal arteries arising from the lateral ventricle. Damage of the subependymal artery that supplies the ventriculofugal arteries caused by coagulation of the choroid plexus at the atrium probably resulted in the infarction in these patients.

Conclusions

Neurosurgeons must be aware of the possibility of LPChA territory infarction during surgery in the atrial or periatrial regions caused by subependymal artery obstruction after manipulating or coagulating the choroid plexus near the atrium.

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Masayuki Kanamori, Tomohiro Kawaguchi, Janice M. Nigro, Burt G. Feuerstein, Mitchel S. Berger, Lucio Miele and Russell O. Pieper

Object

Because activation of Notch receptors has been suggested to be critical for Ras-mediated transformation, and because many gliomas exhibit deregulated Ras signaling, the authors measured Notch levels and activation in primary samples and cell lines derived from glioblastoma multiforme (GBM) as well as the contribution of Notch pathway activation to astrocytic transformation and growth.

Methods

Western blot analysis of Notch 1 expression and activation showed that Notch 1 protein was overexpressed and/or activated in Ras-transformed astrocytes, in three of four GBM cell lines, and in four of five primary GBM samples. Expansion of these studies to assess mRNA expression of components of the Notch signaling pathway by cDNA expression array showed that cDNAs encoding components of the Notch signaling pathway, including the Notch ligand Jagged-1, Notch 3, and the downstream targets of Notch (HES1 and HES2), were also overexpressed relative to non-neoplastic brain controls in 23, 71, and 51% of 35 primary GBMs, respectively. Furthermore, inhibition of Notch signaling by genetic or pharmacological means led to selective suppression of the growth and expression of markers of differentiation in cells exhibiting Notch pathway deregulation.

Conclusions

Notch activation contributes to Ras-induced transformation of glial cells and to glioma growth, survival, or both and as such may represent a new target for GBM therapy.

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Tomohiro Kawaguchi, Shinjitsu Nishimura, Masayuki Kanamori, Hiroki Takazawa, Shunsuke Omodaka, Kenya Sato, Noriko Maeda, Yoko Yokoyama, Hiroshi Midorikawa, Tatsuya Sasaki and Michiharu Nishijima

Object

The difference in the hemodynamics of wall shear stress (WSS) and oscillatory shear index (OSI) between ruptured and unruptured aneurysms is not well understood. The authors investigated the hemodynamic similarities and dissimilarities in ruptured and thin-walled unruptured aneurysm blebs.

Methods

Magnetic resonance imaging–based fluid dynamics analysis was used to calculate WSS and OSI, and hemodynamic and intraoperative findings were compared. The authors also compared ruptured and unruptured thin-walled blebs for the magnitude of WSS and OSI.

Results

Intraoperatively, 13 ruptured and 139 thin-walled unruptured aneurysm blebs were identified. Twelve of the ruptured (92.3%) and 124 of the unruptured blebs (89.2%) manifested low WSS and high OSI. The degree of WSS was significantly lower in ruptured (0.49 ± 0.12 Pa) than in unruptured (0.64 ± 0.15 Pa; p < 0.01) blebs.

Conclusions

Ruptured and unruptured blebs shared a distinctive pattern of low WSS and high OSI. The degree of WSS at the rupture site was significantly lower than in the unruptured thin-walled blebs.

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Ryuta Saito, Toshihiro Kumabe, Takashi Inoue, Shihomi Takada, Yoji Yamashita, Masayuki Kanamori, Yukihiko Sonoda and Teiji Tominaga

Aggressive resection of insular tumors is possible using a meticulous surgical approach based on the regional insular anatomy, with high rates of gross-total resection and low rates of permanent neurological deficits. However, the risk of postoperative morbidities remains high, often caused by disruption of the vascular supply to the surrounding eloquent structures, especially the lenticulostriate arteries (LSAs) that supply the internal capsule. Three-dimensional 3-T time-of-flight (TOF) MR imaging was performed pre- and postoperatively in patients with insuloopercular gliomas. This 3D 3-T TOF MR imaging clearly visualized the LSAs and the relationships with the tumor margins. These findings were confirmed intraoperatively. Three-dimensional 3-T TOF MR imaging of the LSAs in patients with insuloopercular gliomas can help to maximize the extent of resection without neurological complications, preserve the LSAs during surgery, and assist in patient selection.

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Tomohiro Kawaguchi, Toshihiro Kumabe, Ryuta Saito, Masayuki Kanamori, Yoji Yamashita, Yukihiko Sonoda and Teiji Tominaga

Object

Maximized tumor resection and minimized surgical morbidity are extremely important in the treatment of children with malignant neuroepithelial tumors. However, the indications for repeat surgery for these tumors remain unclear. The present study investigated the clinical significance and limitations of repeat resection for these tumors.

Methods

This study included 61 consecutive pediatric patients with malignant neuroepithelial tumor, histologically diagnosed as WHO Grades III and IV. All patients were initially treated between January 1997 and March 2011 and had follow-up of more than 2 years. The number of surgeries, presence of leptomeningeal dissemination, survival, WHO grade, and Eastern Cooperative Oncology Group performance status before and after surgery were retrospectively reviewed.

Results

Repeat resections were performed for 21 patients (34.4%). Eastern Cooperative Oncology Group performance status was not aggravated by surgery, even after multiple operations. The 5-year survival rates of patients who received single and repeat surgery were 58.6% and 38.7%, respectively (p = 0.12). The mean interval between initial surgery and leptomeningeal dissemination detection was 331 ± 108 days in the single-surgery group and 549 ± 122 days in the repeat-surgery group (p = 0.19). The median survival time after leptomeningeal dissemination was 580 days in the single-surgery group and 890 days in the repeat-surgery group (p = 0.74).

Conclusions

Repeat resection with minimized surgical morbidity is an effective method to achieve better local control of pediatric malignant neuroepithelial tumors. Leptomeningeal dissemination was a leading cause of death, but repeat surgery did not increase the frequency of death.

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Yukihiko Sonoda, Toshihiro Kumabe, Shin-Ichiro Sugiyama, Masayuki Kanamori, Yoji Yamashita, Ryuta Saito, Hisanori Ariga, Yoshihiro Takai and Teiji Tominaga

Object

Intracranial germ cell tumors (GCTs) originating in the basal ganglia are rare. The authors investigated factors related to the diagnosis of these lesions as well as outcome in order to help decrease the time to diagnosis and improve treatment efficacy.

Methods

The authors reviewed the clinical features of 142 cases of intracranial GCT in their institute. Fourteen cases of basal ganglia GCT were identified. The symptoms, neuroimaging findings, delay between symptom onset and diagnosis or treatment, initial and further treatment, and outcome were investigated.

Results

Major symptoms were motor weakness and precocious puberty. Gadolinium-enhanced T1-weighted MR images showed enhancement in 8 of 11 patients examined, but only slight hyperintensity without enhancement in 2 patients. Ipsilateral peduncle and hemispheric atrophy were found in 3 and 4 patients, respectively. Cases of basal ganglia GCT were characterized by a longer delay from the initial neuroimaging examination to diagnosis compared with GCT in other regions. Five patients had aggravated hemiparesis in the extremities due to the delay in diagnosis. Despite good response to the initial therapy, 5 patients experienced recurrence; 2 of these 5 had malignant GCTs, and 3 had been treated only with chemotherapy or radiochemotherapy with insufficient radiation dose and field. Finally, the 2 patients with malignant GCTs died of the disease, and 1 died of aspiration pneumonia due to dissemination around the brainstem.

Conclusions

Early diagnosis requires MR imaging with administration of contrast medium in young patients presenting with motor weakness and/or precocious puberty. Serial neuroimaging studies should be performed if any tiny lesion is detected in the basal ganglia. Since insufficient treatment resulted in early recurrence, radiation therapy with adequate dose and field is essential.

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Masayuki Kanamori, Toshihiro Kumabe, Ryuta Saito, Yoji Yamashita, Yukihiko Sonoda, Hisanori Ariga, Yoshihiro Takai and Teiji Tominaga

Object

This study retrospectively analyzed the long-term outcomes of 108 consecutive patients to establish the classification and optimal treatment strategy for each subgroup of newly diagnosed germ cell tumors (GCTs).

Methods

A retrospective review of medical records from the authors' department between April 1989 and March 2007 identified 108 patients with newly diagnosed intracranial GCT. The diagnoses were germinoma in 83 patients, and nongerminomatous GCT (NGGCT) in 25 patients.

Results

In patients with germinoma, the 10-year overall and progression-free survival (PFS) rates at a median follow-up period of 99 months were 86 and 74%, respectively. Recurrences developed during a range of 6 to 153 months (median 26 months) after starting the initial therapy. Patients treated only with chemotherapy demonstrated a shorter PFS rate, and patients treated with chemotherapy followed by reduced-dose radiation therapy to the whole ventricle, whole brain, or craniospinal axis showed significantly better PFS than patients treated with only radiation or reduced-dose radiation therapy to the focal field. Nongerminomatous GCTs were divided into good, intermediate, and poor prognosis groups as proposed by the Japanese Pediatric Brain Tumor Study Group. In the good and intermediate prognosis groups, the 10-year overall and PFS rates were 100 and 93%, respectively. In the poor prognosis group, the 3-year overall and PFS rates were 56 and 29%, respectively. All patients with NGGCTs, in whom the lesions on MR imaging disappeared after combination therapies consisting of resection, radiation therapy, and chemotherapy, remained alive.

Conclusions

Chemotherapy followed by reduced-dose radiation therapy covering the whole ventricle improves the prognosis for patients with germinoma. Combined therapy of radiation therapy, chemotherapy, and radical resection as an initial or salvage treatment achieved excellent tumor control in the intermediate prognosis NGGCT group. The outcomes were still dismal in the poor prognosis NGGCT group, so initial therapy should target complete disappearance of all lesions on MR imaging.

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Tomohiro Kawaguchi, Toshihiro Kumabe, Ryuta Saito, Masayuki Kanamori, Masaki Iwasaki, Yoji Yamashita, Yukihiko Sonoda and Teiji Tominaga

Object

Maximum resection of gliomas with minimum surgical complications usually leads to optimum outcomes for patients. Radical resection of insulo-opercular gliomas is still challenging, and selection of ideal patients can reduce risk and obtain better outcomes.

Methods

This retrospective study included 83 consecutively treated patients with newly diagnosed gliomas located at the insulo-opercular region and extending to the sylvian fissure around the primary motor and somatosensory cortices. The authors selected 4 characteristics as surgical indicators: clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus.

Results

Univariate analysis showed that tumors with clear boundaries were associated with higher rates of gross-total resection than were tumors with ambiguous boundaries (75.7% vs 19.6%). Tumors with negative enhancement compared with enhanced tumors were associated with lower frequency of tumor progression (32.0% vs 81.8%, respectively) and lower rates of surgical complications (14.0% vs 45.5%, respectively). Tumors with intact lenticulostriate arteries were associated with higher rates of gross-total resection than were tumors with involved lenticulostriate arteries (67.3% vs 11.8%, respectively). Tumors with intact superior extremity of the central insular sulcus were associated with higher rates of gross-total resection (57.4% vs 20.7%, respectively) and lower rates of surgical complications (18.5% vs 41.4%, respectively) than were tumors with involved anatomical structures. Multivariate analysis showed that clear tumor boundaries were independently associated with gross-total resection (p < 0.001). Negative enhancement was found to be independently associated with surgical complications (p = 0.005), overall survival times (p < 0.001), and progression-free survival times (p = 0.004). Independent associations were also found between intact lenticulostriate arteries and gross-total resection (p < 0.001), between intact lenticulostriate arteries and progression-free survival times (p = 0.026), and between intact superior extremity of the central insular sulcus and gross-total resection (p = 0.043). Among patients in whom all 4 indicators were present, prognosis was good (5-year survival rate 93.3%), resection rate was maximal (gross-total resection 100%), and surgical complication rate was minimal (6.7%). Also among these patients, overall rates of survival (p = 0.003) and progression-free survival (p = 0.005) were significantly higher than among patients in whom fewer indicators were present.

Conclusions

The authors propose 4 simple indicators that can be used to identify ideal candidates for radical resection of insulo-opercular gliomas, improve the outcomes, and promote maximum resection without introducing neurological complications. The indicators are clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus.