Publications by authors named "Junichi Yoshimura"

40 Publications

Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas.

Diagnostics (Basel) 2021 Apr 9;11(4). Epub 2021 Apr 9.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.

Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of K27M mutation was achieved in only one case (10%); K27M mutation was suspected in three other cases (30%). K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite K27M or definite wildtype) tended to be younger (median 7.5 years vs. 40.5 years; = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.
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http://dx.doi.org/10.3390/diagnostics11040681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070169PMC
April 2021

Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children's Cancer Group.

Brain Tumor Pathol 2021 Apr 11;38(2):109-121. Epub 2021 Mar 11.

Department of Neuropathology, Aichi Medical University, Institute for Medical Science of Aging, Aichi, Japan.

We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM-/GFAP-, NM +/GFAP-, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM-/GFAP-, NM + /GFAP-, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP-  and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP-  medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.
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http://dx.doi.org/10.1007/s10014-021-00396-0DOI Listing
April 2021

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma.

J Neuropathol Exp Neurol 2021 01;80(2):129-136

Department of Pathology, Brain Research Institute, Niigata University.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
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http://dx.doi.org/10.1093/jnen/nlaa141DOI Listing
January 2021

[Surgical Case of Accidental Infantile Acute Subdural Hematoma Caused by Household Minor Head Trauma:Hyperperfusion during Postoperative Hemispheric Hypodensity, Namely "Big Black Brain"].

No Shinkei Geka 2020 Sep;48(9):841-847

Department of Neurosurgery, Nagano Red Cross Hospital.

We experienced a case of an accidental infantile acute subdural hematoma caused by household minor head trauma(Nakamura type I intracranial hemorrhage)with postoperative hemispheric hypodensity lesion(Big Black Brain)whose pathophysiology was analyzed using perfusion MRI. A ten-month-old boy was admitted to our hospital in a comatose state. His mother revealed that the boy suffered a fall from a sofa bed. A CT scan indicated massive acute subdural hematoma in the left cerebral hemisphere. Emergency craniotomy and hematoma evacuation were performed. On postoperative day 3, CT revealed hemispheric hypodensity, and the boy suffered from status epilepticus. MRI on the following day showed widespread white matter hyperintensity in diffusion-weighted images, and MRA demonstrated dilation of the middle cerebral artery. Perfusion MRI using the dynamic susceptibility contrast method revealed a marked increase in cerebral blood flow in the left hemisphere. These abnormal MRI and MRA findings disappeared on postoperative day 13. Status epilepticus also improved upon administration of multi-antiepileptic drugs. Fundoscopy findings on postoperative day 3 showed small bilateral petechial or brush retinal hemorrhages. However, whole-body examination did not show any problems, and was consistent with the mother's account. Thus, we judged non-abusive head trauma. Although follow-up MRI showed diffuse atrophy of the left cerebral hemisphere, the boy aged well without obvious paresis or verbal developmental delay as judged by a follow-up more than a year later. Based on these results, we speculated that hyperperfusion caused by dilation of the cerebral artery was related to the postoperative hemispheric hypodensity, namely "Big Black Brain".
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http://dx.doi.org/10.11477/mf.1436204281DOI Listing
September 2020

MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas.

Front Oncol 2019 21;9:1568. Epub 2020 Jan 21.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase () promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with K27M and G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with gene mutation showed promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response to ALK2 inhibitor K02288 treatment . We confirmed that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.
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http://dx.doi.org/10.3389/fonc.2019.01568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985080PMC
January 2020

Pineal Region Germinoma in the Seventh Decade of Life: A Case Report.

NMC Case Rep J 2019 Aug 11;6(3):75-78. Epub 2019 Jun 11.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Niigata, Japan.

Germ cell tumors typically occur in children and adolescents. We here report a rare case of pineal region germinoma in the seventh decade of life. A 62-year-old man presented with double vision. Computerized tomography and magnetic resonance imaging (MRI) identified a heterogeneously enhanced tumor with calcification in the pineal region with ventricular dilatation due to aqueduct stenosis. The tumor had not been observed at all on MRI obtained 2 years previously. The patient underwent endoscopic biopsy and third ventriculostomy for the obstructive hydrocephalus. The tumor was histopathologically diagnosed as a pure germinoma. The patient underwent radiomonotherapy, resulting in his complete remission, which was confirmed by a series of follow-up MRI studies and hematological examinations. Intracranial germinoma should be considered in the differential diagnosis of pineal region tumors regardless of age, even though the tumor was undetectable on the previous neuroimaging.
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http://dx.doi.org/10.2176/nmccrj.cr.2018-0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692596PMC
August 2019

Detectability of the choroid plexus of the third ventricle with magnetic resonance ventriculography.

Jpn J Radiol 2019 Jun 23;37(6):449-457. Epub 2019 Apr 23.

Department of Radiology and Radiation Oncology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimati-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.

Purpose: To clarify the detectability of the choroid plexus of the third ventricle (ChPl3V) with magnetic resonance ventriculography (MRVn) employing a steady-state free precession (SSFP) sequence in comparison to surgical endoscopic movies as a golden standard, as we encountered some clinical cases of total agenesis of corpus callosum (ACC) where we could not recognize the choroid plexus of the third ventricle and found no previous article addressing this problem.

Materials And Methods: This retrospective study included consecutive patients from 2010 to 2016 for whom endoscopic evaluation of the third ventricle was conducted. The anterior portion of the right and left streaks of ChPl3V was evaluated in 8 patients on 16 sites, while the posterior portion of both streaks of ChPl3V was evaluated in 13 patients on 26 sites. Sensitivity of MRVn to visualize ChPl3V with endoscopic movies as the golden standard was calculated.

Results: Sensitivity of MRVn in visualizing the anterior portion of ChPl3V was 0.813, and that for the posterior portion 0.692. The anterior portion of ChPl3V was visualized in all cases where no tumor contacted the foramen of Monro.

Conclusion: MRVn visualizes the anterior portion of ChPl3V with significant sensitivity and the posterior portion with lower one.
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http://dx.doi.org/10.1007/s11604-019-00834-2DOI Listing
June 2019

Polysomnography as an indicator for cervicomedullary decompression to treat foramen magnum stenosis in achondroplasia.

Childs Nerv Syst 2018 11 29;34(11):2275-2281. Epub 2018 Jun 29.

Department of Neurosurgery, Brain Research Institute, University of Niigata, 1-757, Asahimachi-dori, Chuo-ku,, Niigata City, Niigata, 951-8585, Japan.

Objective: Management of cervicomedullary compression due to foramen magnum stenosis in achondroplasia remains controversial, especially for patients with no symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG) as an indicator for cervicomedullary decompression treatment.

Methods: We retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months) treated from 2008 to 2015. All patients were examined by PSG, magnetic resonance imaging (MRI), and otolaryngeal fibroscopy. We analyzed demographic data, clinical presentation, degree and type of respiratory impairment, severity of foramen magnum stenosis and concomitant cervicomedullary compression, treatment (conservative or surgical), and clinical outcome.

Results: Eight of nine patients presented with no severe symptoms in the daytime. However, MRI revealed four severe, four moderate, and one mild case of cervicomedullary compression, and PSG demonstrated severe sleep apnea in four cases and moderate sleep apnea in five cases. All sleep apnea cases were obstructive or obstructive-dominant. Fibroscopy revealed no upper airway stenosis in six cases and mild stenosis in three cases. Four patients who had severe sleep-related respiratory disturbance on PSG and severe or moderate cervicomedullary compression were treated by cervicomedullary decompression. Three of these patients demonstrated improved sleep respiration soon after surgery, while one required temporary tracheostomy due to bilateral vocal cord paralysis caused by compression during intratracheal intubation.

Conclusion: Polysomnography can be a useful indicator for cervicomedullary decompression surgery, especially in cases of seemingly asymptomatic achondroplasia with severe foramen magnum stenosis.
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http://dx.doi.org/10.1007/s00381-018-3880-0DOI Listing
November 2018

MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas and MGMT Silencing to Temozolomide Sensitivity in IDH-Mutant Gliomas.

Neurol Med Chir (Tokyo) 2018 Jul 31;58(7):290-295. Epub 2018 May 31.

Department of Neurosurgery, Brain Research Institute, Niigata University.

Histone H3 mutations are frequently found in diffuse midline gliomas (DMGs), which include diffuse intrinsic pontine gliomas and thalamic gliomas. These tumors have dismal prognoses. Recent evidence suggests that one reason for the poor prognoses is that O-methylguanine-DNA methyltransferase (MGMT) promoter frequently lacks methylation in DMGs. This review compares the epigenetic changes brought about by histone mutations to those by isocitrate dehydrogenase-mutant gliomas, which frequently have methylated MGMT promoters and are known to be sensitive to temozolomide.
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http://dx.doi.org/10.2176/nmc.ra.2018-0044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048353PMC
July 2018

[Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid Processes:A Case Report].

No Shinkei Geka 2018 Jan;46(1):53-59

Department of Neurosurgery, Nagano Red Cross Hospital.

We report a case of bilateral internal carotid artery(ICA)dissection associated with bilateral elongated styloid processes(ESPs). A 46-year-old man presented with transient aphasia and left visual disturbance at a business meeting. He complained of a foreign body sensation in his throat during swallowing for two years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the left corona radiata. Magnetic resonance angiography(MRA)revealed string signs bilaterally in the cervical ICAs. The patient was diagnosed with bilateral idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three-dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA showed complete normalization of bilateral ICAs after neck rest and anti-platelet therapy, following which, clopidogrel was stopped. The patient wore a soft cervical collar until the operation, to avoid contact between the ESPs and ICAs due to changes in head position. Bilateral ESP resection was performed to prevent recurrence of cerebral ischemic events caused by ICA dissection. The patient was discharged one week after the surgery without any neurological deficit. There was no recurrence of symptoms during the next eight months after the operation.
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http://dx.doi.org/10.11477/mf.1436203675DOI Listing
January 2018

Adult Chiari Type 1 Malformation with Holocord Syringomyelia Associated with Sagittal Synostosis.

NMC Case Rep J 2018 Jan 17;5(1):27-30. Epub 2017 Nov 17.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Niigata, Japan.

Craniosynostosis associated with Chiari malformation (CM) is usually found in infants with an underdeveloped posterior fossa. We here present a case of adult craniosynostosis, CM, and symptomatic syringomyelia caused by the protrusion of the posterior rim of the foramen magnum without a tight posterior fossa. A 22-year-old woman with an abnormal head shape and forearm hypesthesia was given a diagnosis of sagittal suture synostosis with CM and syringomyelia caused by foramen magnum stenosis. She underwent foramen magnum decompression with a C1 laminectomy without cranial vault expansion or duraplasty. Her symptoms and radiographical findings improved after surgery. In cases of non-operative craniosynostosis with CM, clinicians should be alert to late-onset syringomyelia and choose surgical strategies according to the pathophysiology.
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http://dx.doi.org/10.2176/nmccrj.cr.2017-0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767483PMC
January 2018

Third Ventricle Germ Cell Tumor Originating from the Infundibulum with Rapidly Expansive Enlargement.

Pediatr Neurosurg 2018 26;53(1):49-54. Epub 2017 Sep 26.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

We present a pediatric case of a rapidly expanding third ventricle germ cell tumor (GCT). A 14-year-old boy suffered from gradual-onset central diabetes insipidus (DI) and received desmopressin treatment. Magnetic resonance imaging (MRI) showed nonspecific findings of the pituitary-hypothalamic axis. Nine months after the initial DI diagnosis, he developed progressively worsening headache. MRI demonstrated a third ventricle tumor causing noncommunicating hydrocephalus, although an MRI 16 weeks before admission did not show the lesion. We performed gross total resection (GTR) of the tumor in 2 stages: a translamina terminalis approach and an extended transsphenoidal approach. The lesion was histologically diagnosed as immature teratoma with some germinoma. His noncommunicating hydrocephalus resolved after surgery. Through postoperative radiochemotherapy (whole ventricle: 23.4 Gy/13 fractions, tumor bed: 27.0 Gy/15 fractions, and 3 courses of carboplatin-etoposide), he has was in complete remission at the 3-year follow-up and has continued his high school program. This case suggests the following: (1) a mixed GCT originating from the neurohypophysis/infundibulum can show rapidly expansive growth in a child with central DI; (2) GTR and adjuvant radiochemotherapy can result in a good therapeutic outcome in rapidly expanding GCT; and (3) the extended transsphenoidal approach is a complementary approach to transcranial resection of anterior third ventricle GCTs.
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http://dx.doi.org/10.1159/000480021DOI Listing
July 2018

Perifocal Inflammatory Reaction with Volume Fluctuation Caused by Diagnostic Radiation-Induced Regression in Germinoma Makes Histological Diagnosis Difficult despite Its Disappearance following Treatment: A Significant Pitfall and Countermeasures to It.

Pediatr Neurosurg 2017 11;52(2):87-92. Epub 2016 Nov 11.

Department of Neurosurgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.

We present a pediatric case of neurohypophyseal germinoma with a perifocal inflammatory reaction (PIR) with volume fluctuation caused by diagnostic radiation-induced regression (DRIR). On-target biopsy failed to confirm the histology because PIR hardly contained any germinoma cells. DRIR-related fluctuation of the tumor volume disguised germinoma as inflammation. We analyzed the cerebrospinal fluid (CSF) and detected a high level of placental alkaline phosphatase (PLAP), which demonstrated the neurohypophyseal lesion to be germinoma and brought the patient from successful radiochemotherapy up to complete remission. PIR adjacent to the germinoma (PIRAG) disappeared completely following radiochemotherapy, although it contained almost no germinoma cells. Examination of the CSF-PLAP level can complement the diagnosis of germinoma and will decrease the risk of misdiagnosis. Neurosurgeons should keep in mind PIRAG, DRIR, and the diagnostic value of CSF-PLAP when germinoma is suspected.
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http://dx.doi.org/10.1159/000450583DOI Listing
March 2017

Mobile spinal enterogenous cyst resulting in intermittent paraplegia in a child: case report.

J Neurosurg Pediatr 2016 Oct 3;18(4):448-451. Epub 2016 Jun 3.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata City; and.

The authors report the case of a mobile spinal enterogenous cyst in a 2-year-old boy, who was admitted to the hospital several times for intermittent paraplegia. Magnetic resonance imaging and CT revealed an isolated cyst in the lumbar spinal canal. The symptoms were caused by transient myelopathy of the conus medullaris and radiculopathy of the cauda equina due to the changing size and location of the cyst. The cyst was surgically extirpated, after which the symptoms resolved. The histopathological diagnosis was enterogenous cyst. The clinical history of intraspinal enterogenous cyst is usually progressive. Mobility and changes in size are rare pathophysiological findings. The authors speculate that the cyst wall did not adhere to the surrounding structures and had ruptured and quickly reformed. Enterogenous cyst should be considered in the differential diagnosis of spinal intradural cysts in children with radiculomyelopathy.
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http://dx.doi.org/10.3171/2016.4.PEDS15666DOI Listing
October 2016

Long-term outcomes in patients with pineal nongerminomatous malignant germ cell tumors treated by radical resection during initial treatment combined with adjuvant therapy.

Acta Neurochir (Wien) 2015 Dec 20;157(12):2175-83. Epub 2015 Oct 20.

Department of Neurosurgery, Brain Research Institute, University of Niigata, 1-757, Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8585, Japan.

Background: For pineal nongerminomatous malignant germ cell tumors (NGMGCTs), we mainly performed radical tumor resection during initial treatment combined with adjuvant therapy.

Methods: We retrospectively analyzed 17 patients treated for pineal NGMGCTs between 1986 and 2007 at the University of Niigata.

Results: Twelve patients underwent total or subtotal resection of their tumor via the occipital transtentorial approach. Five patients underwent partial resection, and four of them later underwent total resection by salvage surgery. After surgery, eight patients were treated with combined radiochemotherapy including whole-brain irradiation, two received radiation monotherapy, one had chemotherapy with local irradiation, and six were treated with chemotherapy alone. The median follow-up period for surviving patients was 179 months. The 10-year overall survival and progression-free survival rates for the radiochemotherapy group were both 75.0 % (two patients had a recurrence and died); the rates for other adjuvant therapies were 77.8 % (two died) and 22.2 % (seven had a recurrence), respectively. Radiochemotherapy was significantly associated with an increased rate of progression-free survival compared with the other adjuvant therapies (p = 0.0396).

Conclusions: For pineal NGMGCTs, initial treatment strategies including gross total resection of the tumor before or after whole-brain irradiation and chemotherapy provided good therapeutic outcomes. Obtaining complete remission of the primary tumor, irrespective of the timing of surgical resection (i.e., before or after adjuvant therapies), or complete response by neoadjuvant radiochemotherapy during an initial treatment appears to be essential for improving therapeutic outcomes of intracranial NGMGCTs.
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http://dx.doi.org/10.1007/s00701-015-2614-2DOI Listing
December 2015

Limitations of Neuroendoscopic Treatment for Pediatric Hydrocephalus and Considerations from Future Perspectives.

Neurol Med Chir (Tokyo) 2015 28;55(8):611-6. Epub 2015 Jul 28.

Brain Research Institute, University of Niigata.

Neuroendoscopy has become common in the field of pediatric neurosurgery. As an alternative procedure to cerebrospinal fluid shunt, endoscopic third ventriculostomy has been the routine surgical treatment for obstructive hydrocephalus. However, the indication is still debatable in infantile periods. The predictors of late failure and how to manage are still unknown. Recently, the remarkable results of endoscopic choroid plexus coagulation in combination with third ventriculostomy, reported from experiences in Africa, present puzzling complexity. The current data on the role of neuroendoscopic surgery for pediatric hydrocephalus is reported with discussion of its limitations and future perspectives, in this review.
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http://dx.doi.org/10.2176/nmc.ra.2014-0433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628151PMC
April 2017

Clinical factors predicting outcomes after surgical resection for sporadic cerebellar hemangioblastomas.

World Neurosurg 2014 Nov 14;82(5):815-21. Epub 2014 Jun 14.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata-City, Japan.

Objective: To determine whether various clinical factors are related to long-term outcomes of patients with sporadic cerebellar hemangioblastomas.

Methods: Subjects included 36 patients (19 men and 17 women) who underwent resection of sporadic hemangioblastoma in the cerebellum. Age at surgery ranged from 17-79 years (mean, 49.7 years). The tumor size, which was defined as the largest diameter of the lesion including the extratumoral cyst, ranged from 10-67 mm (mean, 36.4 mm). Obstructive hydrocephalus secondary to mass effect on the fourth ventricle was present in 21 (58.3%) patients preoperatively.

Results: Total tumor removal was achieved in 31 of 36 patients (86%). In 4 (11%) patients with solid tumors, postoperative hematoma occurred in the removal cavity, and hematoma removal was required immediately after surgery. We followed 30 patients for >12 months after the initial surgery (mean, 72.9 months; range, 12-274 months). Recurrence of hemangioblastoma developed in 4 of 30 patients (13%) at 6 months, 17 months, 6 years, and 22 years after surgery. At the final follow-up examination, 9 (30%) of 30 patients showed some residual neurologic symptoms (poor group), whereas the remaining 21 patients showed no deficits (good group). Using univariate analysis, both age at surgery and tumor characteristics (cystic or solid) were significantly related to long-term patient outcomes (P < 0.05). However, in a multiple logistic regression analysis, only tumor characteristics were correlated with outcomes (P = 0.017). At the final follow-up examination, patients with solid tumors more frequently showed poor outcomes than patients with cystic tumors.

Conclusions: The solid configuration observed on preoperative images of sporadic cerebellar hemangioblastomas is one of the most important clinical factors related to both immediate and long-term outcomes after surgery.
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http://dx.doi.org/10.1016/j.wneu.2014.06.018DOI Listing
November 2014

Successful removal of a huge hypervascular tentorial cavernous angioma after preoperative endovascular embolization.

J Neurosurg Pediatr 2014 Jul 9;14(1):43-7. Epub 2014 May 9.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.

The authors report a rare case of a huge hypervascular tentorial cavernous angioma treated with preoperative endovascular embolization, followed by successful gross-total removal. A 15-year-old girl presented with scintillation, diplopia, and papilledema. Computed tomography and MRI studies revealed a huge irregularly shaped tumor located in the right occipital and suboccipital regions. The tumor, which had both intra- and extradural components, showed marked enhancement and invasion of the overlying occipital bone. Angiography revealed marked tumor stain, with blood supply mainly from a large branch of the left posterior meningeal artery. Therefore, this lesion was diagnosed as a tentorium-based extraaxial tumor. For differential diagnosis, meningioma, hemangiopericytoma, and malignant skull tumor were considered. Tumor feeders were endovascularly embolized with particles of polyvinyl alcohol. On the following day, the tumor was safely gross totally removed with minimum blood loss. Histopathological examination confirmed the diagnosis of cavernous angioma. To date, there have been no reports of tentorium-based cavernous angiomas endovascularly embolized preoperatively. A tentorial cavernous angioma is most likely to show massive intraoperative bleeding. Therefore, preoperative embolization appears to be quite useful for safe maximum resection. Hence, the authors assert that the differential diagnosis of tentorium-based tumors should include tentorial cavernous angioma, for which preoperative endovascular embolization should be considered.
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http://dx.doi.org/10.3171/2014.4.PEDS13628DOI Listing
July 2014

Intraspinal lesions associated with sacrococcygeal dimples.

J Neurosurg Pediatr 2014 Jul 16;14(1):81-6. Epub 2014 May 16.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Japan.

Unlabelled: OBJECT.: Sacrococcygeal dimples in the gluteal fold, also known as coccygeal pits, are observed in 2%-4% of newborns. Sacrococcygeal dimples are not generally considered to be associated with a significant risk of intraspinal anomalies and therefore are not thought to require further radiographic evaluation. Accordingly, the precise incidence and nature of intraspinal lesions that may be associated with sacrococcygeal dimples is unclear. This study was conducted to determine the incidence of intraspinal lesions in patients with intergluteal dimples.

Methods: In this study, the authors used MRI to evaluate 103 children who were seen at the Niigata University Medical and Dental Hospital between 2006 and 2011 because of skin abnormalities in the lumbosacral region. Of these children, 14 were excluded as having a subcutaneous fatty mass, and 5 were excluded because the dimples were above the gluteal fold or did not end at the coccyx. The remaining 84 patients were classified according to whether the bottom of the dimple was visible (shallow) or not (deep). The authors also retrospectively examined other skin abnormalities and coexisting anomalies.

Results: The mean age at the time of MRI evaluation was 11.7 months. Magnetic resonance imaging led to the identification of fibrolipoma of the terminal filum (FTF) in 14 cases (16.7%); 6 of these patients also had a low conus. Classified by depth, there were 58 cases with shallow and 26 with deep dimples. Fibrolipoma of the terminal filum was found in significantly more patients with deep dimples (9 [34.6%]) than in those with shallow dimples (5 [8.6%]). The frequency of other congenital anomalies was significantly higher in patients with FTF-associated dimples (6 [42.9%] of 14) than in those with dimples that were not associated with FTF (9 [12.9%] of 70).

Conclusions: Fibrolipoma of the terminal filum was identified by MRI in 16.7% of patients with sacrococcygeal dimples. The risk of FTF increased when the dimples were deeply excavated or were accompanied by congenital anomalies. Magnetic resonance imaging should be performed to identify intraspinal lesions when there are high risk factors for intraspinal abnormalities, or when an ultrasound screening suggests intraspinal abnormalities.
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http://dx.doi.org/10.3171/2014.4.PEDS13431DOI Listing
July 2014

Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma.

Neuropathology 2014 Feb 29;34(1):1-10. Epub 2013 Jul 29.

Department of Pathology, Brain Research Institute, University of Niigata; Department of Pediatrics and Child Neurology, Oita University Faculty of Medicine, Oita, Japan.

Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.
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http://dx.doi.org/10.1111/neup.12052DOI Listing
February 2014

[Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

No Shinkei Geka 2013 Jun;41(6):499-505

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata-city, Nigata, Japan.

A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.
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June 2013

Factors affecting functional outcomes in long-term survivors of intracranial germinomas: a 20-year experience in a single institution.

J Neurosurg Pediatr 2013 Apr 1;11(4):454-63. Epub 2013 Feb 1.

Department of Neurosurgery, Brain Research Institute, University of Niigata, 1-757, Asahimachi-dori, Chuo-ku, Niigata City, Niigata 951-8585, Japan.

Object: Radiation monotherapy-prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor-is the standard treatment for intracranial germinomas at the authors' institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them.

Methods: The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5-43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors' institution. Thirty patients had germinomas in localized regions and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months.

Results: The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma.

Conclusions: No tumor recurrence occurred in germinoma patients treated with the authors' radiation monotherapy, which appears to be effective enough to cure the tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems to carry the risk of neurocognitive dysfunctions, which are attributable to late adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient's age and the extent of the tumor and with particular care to avoid surgical complications.
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http://dx.doi.org/10.3171/2012.12.PEDS12336DOI Listing
April 2013

Endoscopic biopsies of lesions associated with a thickened pituitary stalk.

Acta Neurochir (Wien) 2013 Jan 30;155(1):119-24; discussion 124. Epub 2012 Oct 30.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata City, Niigata, 951-8585, Japan.

Background: Lesions associated with a thickened pituitary stalk (TPS lesions) revealed by magnetic resonance imaging have a diverse pathology. Accordingly, for clinical decision-making, it is necessary to make a diagnosis based on histopathological examination of the TPS lesions. The objectives of this study were to review endoscopic biopsies of TPS lesions and to assess the surgical strategy for treating these lesions.

Methods: Eleven patients (four males and seven females) aged from 6 to 75 years underwent endoscopic biopsy of a TPS lesion between 2006 and 2011 at University of Niigata. The relationships of the extent of lesions with surgical approaches were retrospectively examined.

Results: Among the 11 patients, a biopsy was performed via an endoscopic transsphenoidal approach for five with intrasellar lesions; via an endoscopic extended transsphenoidal approach for two with localized TPS lesions; and via an endoscopic intraventricular approach for four with the lesion protruding from the infundibulum. Histopathological examinations of all the lesions confirmed diagnoses of germinoma in four patients, hypophysitis in three, Langerhans cell histiocytosis in two, craniopharyngioma in one, and cancer metastasis in one. None of the 11 patients had further deterioration of pituitary function postoperatively.

Conclusions: Endoscopic biopsy of TPS lesions is a less invasive alternative to open biopsy requiring transcranial surgery. The endoscopic transsphenoidal approach is most suitable for biopsies of TPS lesions associated with intrasellar lesions. Otherwise, the endoscopic intraventricular approach seems reasonable for intraventricular lesions protruding from the infundibulum, and the endoscopic extended transsphenoidal approach appears appropriate for localized TPS lesions.
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http://dx.doi.org/10.1007/s00701-012-1543-6DOI Listing
January 2013

Occurrence of metachronous pure germinomas long after treatment of a mixed germ cell tumor containing yolk sac tumor and germinoma.

J Neurosurg Pediatr 2013 Jan 19;11(1):68-73. Epub 2012 Oct 19.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Japan.

The authors report a rare case involving the occurrence of metachronous pure germinomas long after treatment of a mixed germ cell tumor (GCT) categorized as having a poor prognosis. A neurohypophysial germinoma occurred 4 years and 6 months after the initial treatment of a mixed pineal GCT containing a yolk sac tumor and a germinoma. Furthermore, intramedullary germinomas occurred 21 years after the initial treatment of the mixed GCT and 15 years after the second treatment of the neurohypophysial germinoma. The neurohypophysial germinoma was not confirmed histopathologically, but the intramedullary germinoma was histopathologically diagnosed as a pure germinoma. Serum α-fetoprotein levels at the second neurohypophysial and third intramedullary occurrences of the germinomas were less than 10 ng/ml. Therefore, no yolk sac components seemed to be contained in the tumors. The second neurohypophysial and third intramedullary germinomas might be recurrences of the germinoma component of the pineal mixed GCT, which consisted of a yolk sac tumor and a germinoma. However, it seems very unlikely that only the germinoma, categorized in the good prognosis group, would be the only one to recur. Hence, it seems plausible that both the second and the third occurrences of pure germinoma were de novo metachronous GCTs arising after the pineal mixed GCT was cured. The authors' case indicates the possibility of multicentric GCTs in the CNS.
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http://dx.doi.org/10.3171/2012.9.PEDS12151DOI Listing
January 2013

An organic light-emitting diode display for use in neuroendoscopic surgery in the ventricle.

Acta Neurochir (Wien) 2012 Aug 2;154(8):1523-5; discussion 1525. Epub 2012 May 2.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Asahimachi 1-757, Niigata, Japan.

The organic light-emitting diode (OLED) display delivers a bright and high-contrast image compared to the liquid crystal display. The first experience of neuroendoscopic surgery using an OLED display was reported and its stereoscopic effect emphasized.
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http://dx.doi.org/10.1007/s00701-012-1348-7DOI Listing
August 2012

The effects of temozolomide delivered by prolonged intracerebral microinfusion against the rat brainstem GBM allograft model.

Childs Nerv Syst 2012 May 6;28(5):707-13. Epub 2012 Mar 6.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Objective: Diffuse intrinsic brainstem gliomas are considered to be inoperable. We report our initial experience of temozolomide (TMZ) administration into brainstem by intracerebral (i.c.) microinfusion using a rat brainstem glioblastoma allograft model.

Methods: Forty-eight Fischer 344 female rats were used. In a feasibility study, various doses of i.c.-TMZ (1-10 mg) were administered into the brainstem using AlzetTM pumps in order to evaluate survival rates and neurotoxicity. For tumor implantation, rats received an injection of 10(5) 9 L gliosarcoma cells. For local therapy, 5 days after inoculation, a total amount of 1 mg of TMZ or saline was administered into the brainstem at 1 μl/h over 7 days (n = 8/group). For systemic therapy, rats were treated with an orally administered maximum daily dose of 50 mg/kg TMZ for 5 consecutive days. Survival time and neurological deficit were recorded as outcome parameters.

Results: In the neurotoxicity study, low dose TMZ (1 mg) was feasible to be administered into brainstem over 7 days without neurological deficit. Using high dose TMZ (5-10 mg), marked neurotoxic effect was observed. In the brainstem tumor study, survival was significantly prolonged in low dose i.c.-TMZ group compared to control rats (median survival 23.5 versus 29.5 days; p < 0.01). Systemic therapy with maximal oral-TMZ dose resulted in longer survival time compared to low dose i.c.-TMZ group (median survival 33.5 versus 29.5 days; p < 0.01).

Conclusions: i.c.-TMZ is feasible and effective against rat brainstem glioblastoma allograft. However, we could not show superior potential of i.c.-TMZ compared to oral-TMZ administration. Modification of TMZ infusion with systemic therapy warrants future investigations.
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http://dx.doi.org/10.1007/s00381-012-1732-xDOI Listing
May 2012

Adult cerebellopontine angle medulloblastoma originating in the pons mimicking focal brainstem tumor.

J Neuroimaging 2009 Oct;19(4):385-7

Department of Neurosurgery and Center for Integrated Human Brain Science, University of Niigata, Japan.

We herein report a rare case of cerebellopontine angle (CPA) medulloblastoma originating in the brainstem that demonstrated a very unusual clinical presentation and radiological appearances. A 25-year-old female was admitted to our hospital with a right hearing disturbance and a right facial palsy. A small non-enhanced lesion having minimal mass effect in the right CPA was identified by using a 1.5-tesla-MR system, whose size remained almost unchanged a year. The 3-tesla MR images revealed that the precise region was in the right side of the tegmentum of the lower pons to the inferior cerebellar peduncle and the flocculus. MR spectroscopic images using a 3-tesla system revealed a high ratio of choline-to-N-acetylaspartate in the region of interest in comparison to the contra-lateral side. Craniotomy and biopsy were performed. The histopathological diagnosis was medulloblastoma. The patient received craniospinal irradiation and chemotherapy, and achieved complete remission by the time of the follow-up MR images. She is now doing well with a full recovery of the right facial palsy. MR spectroscopic imaging is considered to be quite useful for the management of this rare type of brainstem tumor.
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http://dx.doi.org/10.1111/j.1552-6569.2008.00298.xDOI Listing
October 2009

Endoscopic fenestration of the third ventricle in the reverse direction.

Childs Nerv Syst 2008 Apr 12;24(4):507-8. Epub 2007 Dec 12.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Asahimachi 1, Niigata, 951, Japan.

Introduction: A case of safely treated parasellar cyst by endoscopic fenestration of the third ventricular floor from outside of the ventricle to establish communications between the cyst and the ventricle is reported.

Materials And Methods: During the endoscopic procedures, the anterior commissure and the foramina of Monro could be clearly observed using this approach.

Conclusion: In treating parasellar cysts with thick walls, endoscopic fenestration of the third ventricular floor in the reverse direction, i.e., from inside of the cyst, should be considered.
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http://dx.doi.org/10.1007/s00381-007-0541-0DOI Listing
April 2008
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