Yasuji Miyakita

Publications (24)40.87 Total impact

• Article: Secondary hematological malignancies associated with temozolomide in patients with glioma.

  Hiroyuki Momota, Yoshitaka Narita, Yasuji Miyakita, Soichiro Shibui
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  ABSTRACT: Background The alkylating agent temozolomide (TMZ) is widely used for the treatment of gliomas. Although reports of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) associated with TMZ are accumulating, it remains unclear whether TMZ has the same leukemogenic potential as other alkylating agents.Methods We performed a single-institution retrospective analysis using a database of 359 glioma patients given nimustine (ACNU)-based therapy, TMZ-based therapy, or combination therapy, who were followed up for a minimum of 2 months, between January 1990 and December 2009, at the National Cancer Center Hospital in Japan.ResultsOf the 359 patients, 225 received ACNU alone or ACNU plus other chemotherapeutic drugs (ACNU-based group; median follow-up period, 31.4 mo), 63 patients received ACNU-based therapy followed by TMZ therapy (ACNU-TMZ group; median follow-up period, 19.1 mo), and 71 patients received TMZ alone or TMZ plus other chemotherapeutic drugs (TMZ-based group; median follow-up period, 16.9 mo). Three patients in the ACNU-based group developed MDS/AML (incidence rate: 2.9 cases per 1000 person-years), 2 patients in the ACNU-TMZ group developed MDS/AML (13.0 cases per 1000 person-years), and 1 patient in the TMZ-based group developed ALL (9.9 cases per 1000 person-years).Conclusions Despite the limitations of this study, published reports and our results suggest that TMZ induces secondary hematological malignancies, particularly ALL, and might shorten the latency period when used in combination with other chemotherapeutic agents.
  Neuro-Oncology 03/2013; · 5.72 Impact Factor
• Article: Secondary glioblastomas with IDH1/2 mutations have longer glioma history from preceding lower-grade gliomas.

  Makoto Ohno, Yoshitaka Narita, Yasuji Miyakita, Yuko Matsushita, Akihiko Yoshida, Shintaro Fukushima, Koichi Ichimura, Soichiro Shibui
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  ABSTRACT: Isocitrate dehydrogenase (IDH)1/2 mutations have been proposed as a genetic marker for secondary glioblastoma (sGBM). This study aimed to evaluate the impact of the IDH1/2 mutations on the clinical course and genetic alterations of sGBMs, which histopathologically progressed from lower-grade gliomas. We investigated 18 sGBMs, including 8 sGBMs with IDH1/2 mutations (sGBM-Mut) and 10 with wild-type IDH1/2 (sGBM-Wt). The median overall survival time of patients with sGBM-Mut was significantly longer than that of patients with sGBM-Wt (68.2 vs. 25.3 months). The median time from initial diagnosis to sGBM diagnosis was also significantly longer for sGBM-Mut than for sGBM-Wt (50.1 vs. 13.4 months). There was no difference in the median survival time from the sGBM diagnosis between sGBM-Mut and sGBM-Wt (6.75 vs. 6.8 months). All sGBM-Mut (7 of 7) and 6 of 9 sGBM-Wt had TP53 mutations, and the remaining one-thirds of sGBM-Wt had neither TP53 mutations nor 1p/19q codeletion. These observations suggest that IDH1/2 mutations have an impact on the glioma history of sGBM with different genetic pathway. The aggressive progression to sGBM-Wt suggest the need for more intense treatment to the IDH1/2 wild-type tumors.
  Brain Tumor Pathology 03/2013; · 1.19 Impact Factor
• Article: A case of more than 20 years survival with glioblastoma, and development of cavernous angioma as a delayed complication of radiotherapy.

  Shintaro Fukushima, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Tsuguto Takizawa, Yutaka Takusagawa, Masaya Mori, Koichi Ichimura, Hitoshi Tsuda, Soichiro Shibui
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  ABSTRACT: Glioblastoma (GBM) is the most common malignant CNS neoplasm, the prognosis of which remains poor even after multidisciplinary treatment. The 5-year overall survival rate of GBM is less than 10% and has remained unchanged for more than 50 years. Because GBM patients rarely survive over a decade, only very few cases of delayed complications caused by therapy have been reported. Here, we report the case of a 24-year-old man who is still alive 21 years after surgical resection and chemoradiotherapy for GBM. This patient developed a cavernous angioma 19 years after the initial surgery as a delayed complication of radiotherapy. The diagnosis of the initial tumor was confirmed by histopathological review, which indicated that the tumor had immunohistochemical and genetic profiles consistent with GBM. Long-term survival in the case of this GBM patient likely resulted from a combination of factors, including hypermethylation of the MGMT (O(6) -methyl guanine methyl transferase) CpG island, young age at diagnosis, good performance status, and complete surgical resection of the tumor. To the best of our knowledge, this case report describes one of the longest-surviving GBM patients and is the first on radiation-induced cavernous angioma in a GBM patient.
  Neuropathology 02/2013; · 2.02 Impact Factor
• Article: Management of glioblastoma in an NF1 patient with moyamoya syndrome: a case report.

  Hideyuki Arita, Yoshitaka Narita, Makoto Ohno, Yasuji Miyakita, Yoshiko Okita, Takafumi Ide, Soichiro Shibui
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  ABSTRACT: INTRODUCTION: Glioma and moyamoya syndrome are both potential complications of neurofibromatosis type 1 (NF1). Here, we report the first case of NF1 concomitantly presenting with glioblastoma 10 years after surgical treatment of moyamoya syndrome. CASE REPORT: A 14-year-old boy with NF1 was incidentally diagnosed by magnetic resonance imaging (MRI) with a thalamic tumor during a follow-up for moyamoya syndrome, which had been treated with surgery 10 years earlier. After observation for 36 months, he developed left hemiparesis, and MRI revealed an increase in tumor size and obstructive hydrocephalus due to the tumor. Needle biopsy was performed through small craniotomy, and the histological diagnosis was glioblastoma. After concurrent chemoradiotherapy with 23 cycles of temozolomide, partial response of the tumor was observed. However, 24 months after the start of the initial therapy, the tumor showed regrowth, and the patient died 30 months after the initial therapy. No cerebrovascular events associated with moyamoya syndrome and chemoradiotherapy were observed during the clinical course of glioblastoma. DISCUSSION: Glioblastoma is a fatal disease in children, and our patient successfully received chemoradiotherapy with temozolomide despite the diagnoses of NF1 and moyamoya syndrome. Although radiotherapy or chemotherapy potentially causes cerebrovascular complications, chemoradiotherapy might be feasible for glioblastoma treatment in patients with moyamoya syndrome and NF1. The following issues are discussed in the management of the present case: the indication of biopsy in NF1 cases, the method of surgery, and the treatment protocol for tumors concomitant with moyamoya disease or syndrome.
  Child s Nervous System 10/2012; · 1.54 Impact Factor
• Article: The late recurrence of ganglioneuroma 21 years after initial presentation with neuroblastoma.

  Yoshiko Okita, Yoshitaka Narita, Akihiko Yoshida, Yasuji Miyakita, Makoto Ohno, Masanao Saio, Naoki Yoshimi, Soichiro Shibui
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  ABSTRACT: A 3-year-old boy presented with tumors in the adrenal gland and the right orbit, and was diagnosed with neuroblastoma. After chemotherapy, the tumors were resected and the pathological diagnoses of ganglioneuroblastoma in the adrenal gland and ganglioneuroma in the orbit were made. The tumor relapsed at the intracranial dura mater 21 years after the initial diagnosis, and was diagnosed as ganglioneuroma from a biopsied sample. This case is very unique in that ganglioneuroma matured from ganglioneuroblastoma or neuroblastoma had the late recurrence with 21 years of tumor dormancy.
  Pediatric Hematology and Oncology 09/2012; 29(7):647-51. · 0.89 Impact Factor
• Article: Intravascular lymphoma of the central nervous system presenting as multiple cerebral infarctions.

  Hiroyuki Momota, Yoshitaka Narita, Yasuji Miyakita, Soichiro Shibui
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  ABSTRACT: A 67-year-old woman presented with an acute onset of left-sided weakness. Magnetic resonance (MR) imaging revealed multiple cerebral infarctions and gadolinium-enhanced lesions in both cerebral hemispheres. Her symptoms once improved after starting steroid treatment; however, soon developed consciousness disturbance and hemiparesis on the left side. She was referred to our hospital where she underwent stereotactic needle biopsy, that revealed an intravascular large B-cell lymphoma in the cerebrum. She received high-dose methotrexate chemotherapy followed by whole-brain radiation therapy, and the MR findings improved. However, her medical condition gradually worsened, and she died 6 months after disease onset. Intravascular lymphoma (IVL) limited to the central nervous system (CNS) is very rare, and the optimal treatment for this medical condition has not been established yet. IVLs showing only neurologic manifestations might be overlooked or misdiagnosed as cerebral infarctions. Here, we present a case of CNS IVL, with its radiographic and pathologic features and treatment with high-dose methotrexate chemotherapy.
  Nagoya journal of medical science 08/2012; 74(3-4):353-8.
• Article: IDH1/2 mutation is a prognostic marker for survival and predicts response to chemotherapy for grade II gliomas concomitantly treated with radiation therapy.

  Yoshiko Okita, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Yuko Matsushita, Shintaro Fukushima, Minako Sumi, Koichi Ichimura, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: Reliable prognostic biomarkers of grade II gliomas remain unclear. This study aimed to examine the role of mutations of isocitrate dehydrogenase (IDH1/2), 1p/19q co-deletion, and clinicopathological factors in patients with grade II glioma who were primarily treated with radiotherapy or chemoradiotherapy after surgery. Seventy-two consecutive patients, including 49 cases of diffuse astrocytomas (DA), 4 oligodendrogliomas (OL) and 19 oligoastrocytomas (OA), who underwent treatment from 1991 to 2010 at a single institution were examined. The overall survival (OS) of the DA patients (8.3 years) was significantly shorter than that of the OL and OA patients (11.7 years). IDH1/2 mutations were found in 46.9% of the DA patients and 82.6% of the OL and OA patients. The progression-free survival (PFS) and OS of the patients with IDH1/2 mutations (8.4 and 16.3 years) were significantly longer than those of the patients without IDH1/2 mutations (3.3 and 4.5 years). Among the patients with IDH1/2 mutations, those who were initially treated with chemoradiotherapy including nimustine hydrochloride (ACNU), had significantly longer PFS than those treated with radiotherapy alone, whereas no significant difference in PFS was observed between the chemoradiotherapy and radiotherapy groups in the patients without IDH1/2 mutations. Oligodendroglial tumors, age <40 years, initial Karnofsky performance status (KPS) ≥80, and IDH1/2 mutations were favorable prognostic factors regarding PFS and OS. IDH1/2 mutation was a predictive factor of response to chemoradiotherapy in grade II gliomas. Patients with IDH1/2 mutations may benefit more from chemoraiotherapy than those without IDH1/2 mutations.
  International Journal of Oncology 07/2012; · 2.40 Impact Factor
• Article: Histopathological malignant progression of grade II and III gliomas correlated with IDH1/2 mutation status.

  Makoto Ohno, Yoshitaka Narita, Yasuji Miyakita, Yoshiko Okita, Yuko Matsushita, Akihiko Yoshida, Shintaro Fukushima, Koichi Ichimura, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: The impact of isocitrate dehydrogenase (IDH1/2) mutations on the malignant progression of gliomas was investigated by comparing the histopathological features of 53 grade II and III gliomas after recurrence according to the IDH1/2 status. We identified IDH1/2 mutations in 44.4 % (16 of 36) of astrocytic tumors and 70.6 % (12 of 17) of oligodendroglial tumors. Histopathological malignant progression was observed in 68.8 % (11 in 16) and 55 % (11 in 20) of astrocytic tumors with and without IDH1/2 mutations, respectively. There were 8 secondary glioblastomas (GBM) that had progressed from 5 diffuse astrocytomas (DA) and 3 anaplastic astrocytomas (AA) with IDH1/2 mutations. Seven secondary GBMs were derived from 3 DAs and 4 AAs with wild-type IDH1/2. Malignant progression was observed in 47.1 % (8 of 17) of oligodendroglial tumors. All 12 oligodendroglial tumors with IDH1/2 mutations remained as such without progressing to GBM, whereas 3 of the 5 oligodendroglial tumors without IDH1/2 mutations progressed to GBM at recurrence. In conclusion, grade II and III gliomas developed to more malignant histological types, irrespective of the IDH1/2 mutation status, and the monitoring of the IDH1/2 status could be of value to predict the development of GBM in patients with oligodendroglial tumors.
  Brain Tumor Pathology 07/2012; · 1.19 Impact Factor
• Article: Development of secondary skull sarcoma after treatment for childhood acute myeloid leukemia.

  Makoto Ohno, Yoshitaka Narita, Yasuji Miyakita, Yoshiko Okita, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: Secondary cancer is a serious late complication in childhood leukemia survivors. Here, we report a case of secondary skull sarcoma developing after treatment for childhood acute myeloid leukemia, including bone marrow transplantation (BMT). This patient had breast cancer 1 year before treatment for the skull sarcoma. The patient underwent macroscopic total removal of the skull tumor with bone margin with postoperative radiation therapy and did not develop tumor recurrence for 25 months. Our patient's experience suggests that survivors of childhood leukemia are at risk of developing skull sarcoma and that multi-agent chemotherapy, including anthracycline, TBI used as conditioning for BMT, and development of GVHD, are possible risk factors. Considering the possibility of multiple secondary malignancies in such patients, careful long-term follow up is mandatory.
  Asia-Pacific Journal of Clinical Oncology 06/2012; · 0.58 Impact Factor
• Article: Long-term follow-up of vanishing tumors in the brain: How should a lesion mimicking primary CNS lymphoma be managed?

  Yoshiko Okita, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Shintaro Fukushima, Akiko Maeshima, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: The spontaneous disappearance of a tumor is referred to as a vanishing tumor. Most vanishing tumors in the brain are eventually diagnosed as malignant tumors or multiple sclerosis. However, their long-term clinical course remains unclear. This study aims to elucidate the management of vanishing tumors in the brain. We defined a vanishing tumor as a case in which the tumor spontaneously disappeared or decreased to less than 70% of the initial tumor volume before definitive diagnosis and treatment (other than steroid treatment). Ten cases of vanishing tumors are reviewed. Nine patients underwent biopsy at least once. Five patients, all of whom had malignant tumors (primary central nervous system lymphoma: 4, germinoma: 1) that recurred in 4-45 months (median: 7 months), underwent a second biopsy after the reappearance of the tumors. Five patients (tumefactive demyelinating lesion: 1, undiagnosed: 4) who had no relapse are alive, and their median follow-up time is 44 months. No cases have yet been reported of malignant brain tumors that recurred more than 5 years after spontaneous regression. Patients with vanishing tumors should be followed up carefully by magnetic resonance imaging for at least 5 years, even after the disappearance of an enhancing lesion.
  Clinical neurology and neurosurgery 03/2012; 114(9):1217-21. · 1.30 Impact Factor
• Article: A case of unclassified high-grade glioma with polar spongioblastoma pattern.

  Shintaro Fukushima, Yoshitaka Narita, Aya Shinomiya, Makoto Ohno, Yasuji Miyakita, Yoshiko Okita, Kazuo Hanakawa, Takafumi Ide, Takamasa Kayama, Soichiro Shibui, Hitoshi Tsuda
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  ABSTRACT: Primitive polar spongioblastoma was first described by Russell and Cairns in 1947. However, the polar spongioblastoma pattern is often seen in many neuroepithelial tumors, and this category was deleted in the previous World Health Organization (WHO) classification. In 2010, Nagaishi et al. reported on a case involving a neuroepithelial tumor with the typical histological pattern of polar spongioblastoma and suggested that this tumor might not be suited to any of the neuroepithelial tumors in the current WHO classification. We report on an autopsy case involving an unclassified high-grade glioma with polar spongioblastoma pattern that was very similar to the case described by Nagaishi et al. A 44-year-old man who presented with a headache exhibited a tumor of the right frontal lobe on MRI. Histological diagnosis of the tumor obtained by gross total resection was high-grade glioma, which was composed of the parallel palisading of spindle tumor cells expressing GFAP, without microvascular proliferation (MVP) and necrosis. Conventional chemoradiotherapy was performed, but the case was complicated by cerebrospinal fluid (CSF) dissemination that resulted in multiple extraneural metastases through systemic diversionary CSF shunting. Finally, the patient died approximately 13 months after the initial treatment. Both the cerebral and Douglas pouch tumors that were obtained at autopsy were diagnosed as typical glioblastomas, and they were composed of the proliferation of atypical astrocytes with MVP and pseudopalisading necrosis without the formation of rhythmic palisading. Although the histological findings were different from that of the first operation, immunohistochemical and genetic profiles demonstrated almost the same results. This tumor was not classified as a typical glioblastoma by the initial findings, but it had the nature of a glioblastoma. These findings suggest that the tumor might be classified as a new subset of glioblastoma called glioblastoma with polar spongioblastoma pattern.
  Neuropathology 03/2012; · 2.02 Impact Factor
• Article: Pathological findings and prognostic factors in recurrent glioblastomas.

  Yoshiko Okita, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Shintaro Fukushima, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: Glioblastomas, which are the most common primary intracranial tumor, are associated with the poorest survival time, which is typically 1-2 years. Age at initial diagnosis, Karnofsky performance score, and O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status are the most well-documented predictors of survival in patients with newly diagnosed glioblastoma. Few studies have examined prognostic factors in patients with recurrent glioblastomas. At relapse, the pathological features of glioblastomas are affected by tumor regrowth and the influence of chemoradiotherapy during the initial treatment. Morphological transformations at recurrence include quantitative changes in tumor cells, such as the presence of giant cells and gemistocytic cell formation, radiation necrosis, and vascular structural changes. Therefore, we should carefully examine pathological findings at recurrence. In this report, we analyzed MGMT promoter status, the MIB-1 index, and the pathology of tumor samples at the first (primary tumor) and second (recurrent tumor) surgeries and clarified prognostic factors in patients with recurrent cases. In the multivariate analysis, we showed that MIB-1 indexes at the time of the second surgery (p = 0.004) persisted as a significant independent prognostic factor in survival of patients with recurrent glioblastoma.
  Brain Tumor Pathology 02/2012; · 1.19 Impact Factor
• Article: Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis.

  Ken Hashimoto, Yoshitaka Narita, Yuko Matsushita, Yasuji Miyakita, Makoto Ono, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: O6-methylguanine-DNA-methyl transferase (MGMT), a DNA repair gene, is a key enzyme for predicting the response to both radiotherapy and temozolomide in glioma patients. Data on the MGMT promoter methylation status in relation to the time to develop intracranial new metastasis or local relapse at the surgical site after brain surgery followed by radiotherapy is limited in non-small-cell lung cancer (NSCLC) patients with a single brain metastasis. All 55 patients included in this analysis were NSCLC with a single brain metastasis and had undergone brain surgery followed by radiotherapy. Genomic DNA was extracted from the brain tumour. The DNA was treated with bisulphate and a methylation-specific polymerase chain reaction was performed. Survival was compared by the status of promoter region of MGMT. The time to develop intracranial new metastases or local relapse at the surgical site after treatment in patients with methylation of the MGMT promoter region was 4.0 months (N = 5), while that of the patients without methylation of the MGMT promoter region was 11.5 months (N = 50) (p = 0.37). NSCLC patients with brain metastasis treated by brain surgery followed by radiotherapy may have a higher chance of relapse when the tumour has methylation of the MGMT promoter region.
  Clinical and Translational Oncology 01/2012; 14(1):31-5. · 1.33 Impact Factor
• Article: Management of cytomegalovirus infection in a patient with malignant glioma treated with temozolomide and steroids.

  Yoshiko Okita, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Shoichi Nagai, Soichiro Shibui
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  ABSTRACT: Temozolomide (TMZ) is the standard chemotherapy treatment for glioblastoma. Lymphocytopenia is reported to be the most frequent and severe adverse effect of TMZ and leads to opportunistic infections. Few cases of TMZ-induced cytomegalovirus (CMV) reactivation have so far been reported, and there are no guidelines regarding the use of chemotherapy after recovery from CMV reactivation. We herein report the case of a 45-year-old man with glioblastoma who developed CMV hepatitis following surgery and chemoradiotherapy with concomitant TMZ and steroids. After successful treatment of the CMV infection with an antiviral agent and recovery from the lymphocytopenia were achieved, the patient resumed maintenance therapy with TMZ under careful monitoring of his lymphocyte count and CMV pp65 antigenemia level.
  Internal Medicine 01/2012; 51(20):2967-71. · 0.94 Impact Factor
• Article: Comparison of clinical outcomes of surgery followed by local brain radiotherapy and surgery followed by whole brain radiotherapy in patients with single brain metastasis: single-center retrospective analysis.

  Kenji Hashimoto, Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Minako Sumi, Hiroshi Mayahara, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: Data comparing the clinical outcomes of local brain radiotherapy (LBRT) and whole brain RT (WBRT) in patients with a single brain metastasis after tumor removal are limited. A retrospective analysis was performed to compare the patterns of treatment failure, cause of death, progression-free survival, median survival time, and Karnofsky performance status for long-term survivors among patients who underwent surgery followed by either LBRT or WBRT between 1990 and 2008 at the National Cancer Center Hospital. A total of 130 consecutive patients were identified. The median progression-free survival period among the patients who received postoperative LBRT (n = 64) and WBRT (n = 66) was 9.7 and 11.5 months, respectively (p = .75). The local recurrence rates (LBRT, 9.4% vs. WBRT, 12.1%) and intracranial new metastasis rate (LBRT, 42.2% vs. WBRT, 33.3%) were similar in each arm. The incidence of leptomeningeal metastasis was also equivalent (LBRT, 9.4% vs. WBRT, 10.6%). The median survival time for the LBRT and WBRT patients was 13.9 and 16.7 months, respectively (p = .88). A neurologic cause of death was noted in 35.6% of the patients in the LBRT group and 36.7% of the WBRT group (p = .99). The Karnofsky performance status at 2 years was comparable between the two groups. The clinical outcomes of LBRT and WBRT were similar. A prospective evaluation is warranted.
  International journal of radiation oncology, biology, physics 04/2011; 81(4):e475-80. · 4.59 Impact Factor
• Article: Reactivation of hepatitis B virus after glioblastoma treatment with temozolomide--case report.

  Makoto Ohno, Yoshitaka Narita, Yasuji Miyakita, Hideki Ueno, Takamasa Kayama, Soichiro Shibui
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  ABSTRACT: A 61-year-old man with glioblastoma and positive for hepatitis B surface antigen (HBsAg) developed acute hepatitis due to hepatitis B virus (HBV) reactivation after concomitant postoperative treatment with temozolomide (75 mg/m(2)/day) and radiation therapy (60 Gy in 30 fractions). Corticosteroids were not used during chemo-radiation therapy, and grade 4 lymphocytopenia was observed. The levels of liver function tests (LFTs), including levels of aspartate aminotransferase and alanine aminotransferase, increased 5 weeks after the completion of chemo-radiation therapy, and reached the maximum levels of 1,549 IU/l (normal 13 to 33 IU/l) and 1,653 IU/l (normal 8 to 42 IU/l), respectively, after 2 weeks. At this point, serum HBV-deoxyribonucleic acid (DNA) level had increased to 630-fold over the baseline, and therapy with the antivirus agent entecavir (0.5 mg daily) was started. Over the next 2 weeks, the levels of LFTs and HBV-DNA improved. The present and previous cases suggest that grade 3/4 lymphocytopenia or grade 2 lymphocytopenia with corticosteroid use might have a significant effect on HBV reactivation. To avoid this complication, HBsAg-positive patients with glioblastoma should consult a hepatologist for initiating antivirus therapy before temozolomide treatment.
  Neurologia medico-chirurgica 01/2011; 51(10):728-31. · 0.61 Impact Factor
• Article: p53 abnormality and tumor invasion in patients with malignant astrocytoma.

  Hiroyuki Momota, Yoshitaka Narita, Yuko Matsushita, Yasuji Miyakita, Soichiro Shibui
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  ABSTRACT: Malignant astrocytomas are characterized by diffusely infiltrating nature, and the abnormality of p53 is a cytogenetic hallmark of astrocytic tumors. To elucidate the relationship between p53 abnormality and invasiveness of the tumors, we studied mutation and protein expression of p53 in 48 consecutive patients with malignant astrocytoma (14 anaplastic astrocytomas and 34 glioblastoma multiformes). The tumors were classified into three categories according to the features of magnetic resonance imaging, and 5, 7, and 36 tumors were classified into diffuse, multiple, and single type, respectively. We then examined how these tumor types correlate with MIB-1 staining index, TP53 gene mutation, and p53 protein expression. We found that p53 immunopositivity or TP53 mutation was frequently observed in diffuse and multiple types. These abnormalities of p53 were also associated with high MIB-1 staining index and strong expression of vascular endothelial growth factor. Furthermore, diffuse- and multiple-type tumors were significantly correlated with poor progression-free survival, whereas only multiple-type tumors were significantly correlated with poor overall survival. As diffuse and multiple features on imaging modalities represent invasive characteristics of the tumors, p53 abnormalities may affect the invasive and aggressive nature of malignant astrocytomas.
  Brain Tumor Pathology 10/2010; 27(2):95-101. · 1.19 Impact Factor
• Article: Acute lymphoblastic leukemia after temozolomide treatment for anaplastic astrocytoma in a child with a germline TP53 mutation.

  Hiroyuki Momota, Yoshitaka Narita, Yoshitaka Nariata, Yasuji Miyakita, Ako Hosono, Atsushi Makimoto, Soichiro Shibui
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  ABSTRACT: We present a case of a 12-year-old female with a germline TP53 mutation who presented with anaplastic astrocytoma and subsequent acute lymphoblastic leukemia (ALL) 13 months after starting treatment with temozolomide (TMZ). The patient had no family history of malignancy except her grand father and his siblings. Although alkylating agents such as TMZ are known to induce secondary hematologic malignancy, only several cases of treatment-related acute leukemia have been reported after TMZ-alone chemotherapy for malignant gliomas. We demonstrate a rare case of TMZ-related ALL in a child with glioma possibly associated with a germline TP53 mutation.
  Pediatric Blood & Cancer 09/2010; 55(3):577-9. · 1.89 Impact Factor
• Article: Prognostic value of immunohistochemical profile and response to high-dose methotrexate therapy in primary CNS lymphoma.

  Hiroyuki Momota, Yoshitaka Narita, Akiko M Maeshima, Yasuji Miyakita, Aya Shinomiya, Takashi Maruyama, Yoshihiro Muragaki, Soichiro Shibui
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  ABSTRACT: Several biomarkers have been identified as prognostic factors in primary central nervous system lymphoma (PCNSL). However, the correlation between the histogenetic origin of PCNSL and the response to therapy is still unclear. To elucidate the utility of immunophenotypic markers in predicting clinical outcomes, we investigated 27 immunocompetent patients with PCNSL treated with high-dose methotrexate therapy. Of the 27 patients, 25 received whole-brain radiotherapy after high-dose methotrexate. Immunostaining for CD5, CD10, BCL-6, and MUM-1 was used to determine the immunophenotypic profile of diffuse large B-cell lymphoma of PCNSL. We then evaluated whether immunophenotypic markers were associated with the response to therapy or patients' survival. The response to induction high-dose methotrexate therapy was determined by magnetic resonance imaging after three courses of i.v. high-dose methotrexate. We categorized B-cell lymphomas into three known subtypes: germinal center B-cell (GCB), activated-GCB, and post-GCB subtypes according to immunohistochemical profile. All the BCL-6-positive samples were co-positive for MUM-1 and therefore classified into activated-GCB subtype. BCL-6 expression in this study was associated with poor progression-free survival (P = 0.038). No immunophenotypic markers or subtypes had a significant effect on the response to high-dose methotrexate therapy. However, the response itself was a significant predictor for both progression-free survival (P < 0.001) and overall survival (P = 0.003). Further investigation is needed to assess BCL-6 as a potential prognostic factor in PCNSL.
  Journal of Neuro-Oncology 12/2009; 98(3):341-8. · 3.21 Impact Factor
• Article: A case of metastatic intracranial malignant melanoma mimicking simple subcortical hemorrhage in an elderly woman.

  Yasuji Miyakita, Soichiro Shibui
  Japanese Journal of Clinical Oncology 10/2009; 39(9):621. · 1.78 Impact Factor