Masahiro Ito

NHO Nagasaki Medical Center, Nagasaki, Nagasaki, Japan

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Publications (233)682.91 Total impact

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    ABSTRACT: We report a 64-year-old female case of intractable adult-onset Still’s disease (AOSD). Initial high-dose steroid therapy combined with cyclosporin A was ineffective against macrophage-activation syndrome (MAS), which was accompanied by the systemic type of AOSD. Treatment for MAS with intravenous cyclophosphamide resulted in remission of AOSD and a reduction in the high doses of steroids. Efficacy of biologics against MAS in AOSD is unclear. Cyclophosphamide, a conventional cytotoxic agent, should be considered as one of the therapeutic options for refractory types of AOSD with MAS.
    Preview · Article · Dec 2015

  • No preview · Article · Dec 2015
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    ABSTRACT: After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF(V600E) in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF(V600E) was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.
    Full-text · Article · Nov 2015 · Scientific Reports
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    ABSTRACT: A 63-year-old Japanese woman with a 30-year history of systemic lupus erythematosus developed macrohematuria and massive proteinuria after seroconversion of myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A renal biopsy indicated focal proliferative lupus nephritis (class III A/C) with a fibrous crescent formation. Methylprednisolone pulse therapy (500 mg, 3 successive days) was administered because of progressive proteinuria. Steroid therapy did not suppress the progressive proteinuria; therefore, tacrolimus was added as an alternative immunosuppressive therapy, resulting in the improvement of proteinuria and renal impairment. This case report suggests that MPO-ANCA might play a pathogenic role in the exacerbation of immune-complex-type lupus nephritis.
    No preview · Article · Nov 2015 · Internal Medicine
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    ABSTRACT: Objective: The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. Methods: We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. Results: Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. Conclusions: These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.
    No preview · Article · Sep 2015 · International Journal of Gynecological Cancer
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    ABSTRACT: Key Clinical Message The granulocyte-colony-stimulating factor (G-CSF)-producing esophageal carcinosarcoma is extremely rare in esophageal cancer. In the present case, multidisciplinary therapy, which is surgical resection with preoperative chemotherapy, has been effectively treatment to granulocyte-colony-stimulating factor producing esophageal carcinosarcoma of the esophagus.
    Full-text · Article · Jun 2015
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    ABSTRACT: Granulomatosis with polyangiitis (GPA) sometimes involves the eye orbit; however, choroidal involvements in GPA had been rarely reported. We report a rare case presenting with a choroidal mass in an 83-year-old Japanese woman who presented with left eye pain. Diagnostic biopsy revealed necrotizing vasculitis with infiltrates of inflammatory cells. Diagnosis was localized granulomatosis with polyangiitis. Combined treatments with corticosteroid plus azathioprine resolved the choroidal mass region. Although treatment with corticosteroid and immunosuppressive agents improves the prognosis of the disease, ocular morbidity is still well recognized. Clinicians should consider a differential diagnosis of GPA in patients with inflammatory choroidal tumors.
    Preview · Article · May 2015
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    ABSTRACT: Inflammatory pseudotumor (IPT) is a rare benign condition often misdiagnosed as malignancy. An 80-year-old man was referred to our clinic for an asymptomatic hepatic mass detected on plain abdominal CT. Abdominal ultrasonography identified the lesion as a poorly defined hypoechoic mass. Although a liver biopsy did not provide any evidence of malignancy, imaging modalities suggested a diagnosis of cholangiocarcinoma. The patient underwent left lobectomy, and the pathological findings were consistent with the features of xanthogranulomatous cholangitis. This case is the first report of hepatic IPT originating from xanthogranulomatous cholangitis without symptoms and illustrates the importance of obtaining a preoperative diagnosis in order to avoid a misdiagnosis of malignant tumor.
    No preview · Article · Apr 2015 · Internal Medicine
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    ABSTRACT: Background: Several single nucleotide polymorphisms (SNP) have been identified to be associated with the risk for differentiated thyroid cancer in populations of distinct ethnic background. The relationship of these genetic markers to a benign tumor of the thyroid, follicular adenoma (FA), is not well established. Methods: In a multicenter retrospective case-control study, five thyroid cancer-related SNPs-rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B)-were genotyped in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls. Results: A significant association was found between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000]) and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302 (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI 1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980-1.316]) in this series. A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC (about 10% decrease per each risk allele). NRG1 expression also significantly correlated with that of PTCSC3. Conclusions: Association of rs944289, which was previously known to confer risk for thyroid cancer, with FA, and the correlation between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and imply broader roles of the pathways they underlie in thyroid tumorigenesis, not limited to carcinogenesis.
    No preview · Article · Jan 2015 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: A 50-year-old woman was referred to our hospital for shoulder joint stiffness. She had a history of polyclonal hypergammaglobulinemia and an elevated C-reactive protein level. Her laboratory data revealed an elevated serum immunoglobulin G4 (IgG4) level, hypergammaglobulinemia, and rheumatoid factor positivity in the absence of anticyclic citrullinated peptide antibody. [18(F)]-Fluorodeoxyglucose positron emission tomography showed significant [18(F)]-fluorodeoxyglucose uptake in multiple lymph nodes (axillary, hilar, para-aortic, and inguinal). Biopsy of the inguinal lymph node showed expansion of the interfollicular areas by heavily infiltrating plasma cells, consistent with multicentric Castleman disease (MCD). Immunohistochemical analysis revealed a 37.3% IgG4-positive:IgG-positive plasma cell ratio, indicating overlapping IgG4-related disease. However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD. Corticosteroid treatment resolved the serological and imaging abnormalities. IgG4-related disease can mimic MCD, and it is crucial to distinguish between these two diseases. Serum interleukin-6 and VEGF levels may help to discriminate MCD from IgG4-related disease.
    No preview · Article · Dec 2014 · Modern Rheumatology
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    ABSTRACT: Geographic differences have been reported to affect the morphological and molecular features of papillary thyroid carcinomas (PTCs). The area around Chernobyl is well-known to be iodine-deficient in contrast to Japan, an iodine-rich country. We reviewed histological differences in adult PTC between Ukraine and Japan. In total, 112 PTCs from age- and sex-matched adults (Ukraine 56, Japan 56) were evaluated histologically for several factors including tumor size, capsulation, tumor components (papillary, follicular, solid, trabecular), lymph node metastasis, extrathyroid invasion, lymphocytic infiltration, oxyphilic metaplasia, and MIB-1 index. We demonstrated that tumors were smaller (1.56 vs. 2.13 cm, p<0.05) and more solid and that lymph node metastasis was less frequent (14.3% vs. 48.2%, p<0.001) in Ukrainian cases. PTC subtype distribution was significantly different between the two groups. Solid variant (8.9% vs. 1.8%) and mixed subtypes with solid components were more frequent in Ukrainian patients. In contrast, classical papillary carcinomas were more frequent in Japanese cases (10.7% vs. 50.0%, p<0.001). Marked oxyphilic metaplasia was more common in Ukrainian cases (33.9 % vs. 8.9 %, p<0.001). MIB-1 index was significantly higher in Ukrainian cases (2.9% vs. 1.8%, p<0.001). However, the frequencies of tumor capsule formation and background lymphoid follicle formation around the tumor were similar between groups. Morphological differences in adult PTCs were similar to those in pediatric PTCs as reported previously, suggesting that morphogenesis of PTC is influenced by environmental factors, especially dietary iodine, as well as genetic factors.
    Full-text · Article · Sep 2014 · Endocrine Journal
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    ABSTRACT: Background & aimsThe aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with PBC.Patients and Methods Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (≤ULN), fair (≤1.5 x ULN), or poor (>1.5 x ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status, and histological variables at baseline), biochemical response to treatment, and long-term outcomes were evaluated in 164 Japanese PBC patients.ResultsAnti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse ALP response (OR, 2.78 and 1.85, respectively). Age, anti-gp210 positivity, and anti-centromere positivity were significant risk factors for worse ALT response (OR, 1.05, 4.0, and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse IgM response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11).Conclusions Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.
    No preview · Article · Sep 2014 · Hepatology Research
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    ABSTRACT: The patient was in her sixties who had visited a local physician complaining of abdominal discomfort and was referred to our hospital when abdominal CT showed a pelvic mass. Abdominal contrast-enhanced CT showed a mass, 24 mm in diameter, along a left internal iliac vessel peripheral branch, showing non-uniform contrast enhancement. T2-weighted images on pelvic contrast MRI showed a marginal high signal, with the interior showing a non-uniform contrast effect. The mass was believed to be a sacral nerve-derived schwannoma in light of the site of origin and imaging findings. A malignant tumor could not be ruled out, and a tumorectomy was performed by reduced port surgery. Histopathological findings showed no atypia in the constituent cells, and the patient was diagnosed with a schwannoma. A schwannoma is a tumor generated from Schwann cells, and the frequency of onset in the pelvic retroperitoneum is extremely rare, about 1%. The first-choice treatment is surgical resection, including the capsule, but in surgery in a narrow deep pelvis, as in the present case, laparoscopic surgery is minimally invasive, offers excellent visibility, and is a useful approach.
    Preview · Article · Jan 2014 · Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association)
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    ABSTRACT: Background: The BRAF(V600E) mutation is the most common genetic alteration in papillary thyroid carcinomas (PTCs). Transgenic mice overexpressing BRAF(V600E) in their thyroids under control of the thyroglobulin promoter (Tg-BRAF2 mice) developed invasive PTCs with high penetrance. However, these mice showed elevated thyrotropin (TSH) levels, which also stimulate the proliferation of thyrocytes and tumorigenesis. The purpose of the present study was to investigate how TSH signaling cooperates with BRAF(V600E) in the process of thyroid carcinogenesis. Methods: We crossed Tg-BRAF2 mice with TSH receptor knockout (TshR(-/-)) mice. Four genetically distinct mice groups-Braf(wt)/TshR(+/-) (group 1), Braf(wt)/TshR(-/-) (group 2), Tg-BRAF2/TshR(+/-) (group 3), and Tg-BRAF2/TshR(-/-) (group 4)--were sacrificed at 12 and 24 weeks of age. We performed histopathological analysis. Genomic instability was evaluated by immunofluorescence for p53-binding protein 1 (53BP1) and γH2AX. Invasiveness and genomic instability were also evaluated using thyroid PCCL3 cells expressing BRAF(V600E). Results: Groups 3 and 4 developed distinct neoplasias comparable to human PTCs. Group 3 developed typically larger, more aggressive, invasive tumors compared to group 4. The frequency of 53BP1 and γH2AX foci-indicators of genomic instability--in group 3 was higher than that in group 4. TSH also enhanced invasiveness and genomic instability in PCCL3 cells with BRAF(V600E) expression. Conclusions: These data demonstrate that the TSH signaling confers more aggressive features in BRAF(V600E)-induced thyroid tumors in mice. This might be due, in part, to accelerated genomic instability.
    No preview · Article · Aug 2013 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC. We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining. Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients. These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.
    No preview · Article · Aug 2013 · Liver international: official journal of the International Association for the Study of the Liver
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    ABSTRACT: In a previous report, we proposed that analysis of 53BP1 expression by immunofluorescence could be a useful tool in estimating the level of genomic instability (GIN), as well as the malignant potential, of thyroid tumours. In an attempt to clarify the value of 53BP1 expression as a new molecular marker for the aggressiveness of thyroid papillary microcarcinoma (PMC), we assessed the association between the type of 53BP1 expression and clinicopathological features such as tumour size, extrathyroidal invasion, lymph node metastasis and BRAF(V) (600E) mutation of PMC. A total of 36 surgically resected thyroid tumours, including 13 PMC and 23 conventional papillary thyroid carcinomas (PTC), were available for this study. Analysis using immunofluorescence revealed that the incidence of an abnormal or high DNA damage response (DDR) type of 53BP1 expression was significantly higher in PTC than PMC. BRAF(V) (600E) mutation was not associated significantly with tumour aggressiveness in either PMC or PTC cases. Abnormal/high DDR type of 53BP1 expression was associated closely with both BRAF(V) (600E) mutation and papillary and/or trabecular architecture of PMC. Abnormal/high DDR type of 53BP1 expression might be associated with GIN and papillary/trabecular morphology at an early stage of PTC carcinogenesis through BRAF(V) (600E) mutation.
    No preview · Article · Jul 2013 · Histopathology
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    ABSTRACT: Background: Neuroendocrine tumor (NET) of the thyroid other than medullary carcinoma is extremely rare. We describe here a case of calcitonin-negative small cell neuroendocrine carcinoma (SCNEC), which occurred in a thyroid gland that had previously been irradiated at high dose (60 Gy) for pharyngeal cancer, with molecular analyses for follicular cell origin. Patient findings: The tumor cells were small with fine chromatin, inconspicuous nucleoli, and inapparent cytoplasm, and showed neuroendocrine architectures such as palisading, rosettes, and trabeculae. Mitotic figures were numerous exceeding 10 mitoses per 10 high-power fields. The tumor cells invaded into several vessels and metastasized to regional lymph nodes. Immunohistochemically, the tumor cells were strongly positive for neuroendocrine markers and thyroglobulin (Tg), a marker of thyroid follicular cells but negative for calcitonin and carcinoembryonic antigen (CEA). Expression of Tg and thyrotropin receptor (TSHR) were confirmed by quantitative real-time polymerase chain reaction (RT-PCR). Ki-67 labeling index was more than 70% in the tumor cells. Taken together, the tumor was diagnosed as SCNEC of the thyroid. Genetic analyses also revealed microsatellite abnormalities of the phosphatase and tensin homolog (PTEN) gene, suggesting that functional loss of PTEN contributes to carcinogenesis. Conclusions: This is the first report describing a SCNEC of the thyroid with molecular analyses that provide evidence for a follicular epithelial origin.
    No preview · Article · Jul 2013 · Thyroid: official journal of the American Thyroid Association
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    ABSTRACT: Malignant rhabdoid tumor is a rare tumor occurring mostly in the neonatal kidneys and central nervous system. Cutaneous malignant rhabdoid tumors are extremely rare in adults. The aim of the study was to report on the clinical, histologic, and immunophenotypic characteristics of this cutaneous malignant rhabdoid tumor which developed in an adult. A 27-year-old male complained of a right palm neoplasm that had been present for 6 months, which was initially diagnosed as an epithelioid sarcoma by biopsy. However, detailed investigation with immunohistochemistry enabled us to make a diagnosis of a rhabdoid tumor. The patient underwent radical abrasion, chemotherapy, and irradiation, and has survived for 1 year without relapse. Only 20 adult cases have been reported thus far in the English literature. We are reporting the 21(st) case, who remains disease-free at 12 months. Complete resection and local irradiation may increase survival, because there is no standard and reliable curative chemotherapeutic regimen.
    Full-text · Article · Jul 2013 · Rare tumors
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    ABSTRACT: To explore mutations in serine/threonine kinase 11 (STK11) gene in Peutz-Jeghers syndrome (PJS) with gastrointestinal (GI) hamartomatous polyps. Six Japanese PJS patients in 3 families were enrolled in this study. Each of the cases had hamartomatous polyposis in the gastrointestinal tract, including the small intestine, along with mucocutaneous hyperpigmentation. Narrow-band imaging (NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI lesions. NBI magnification findings could be classified into three groups (type A, type B, or type C). Endoscopic polypectomy was performed using double-balloon enteroscopy or colonoscopy. Genomic DNA was extracted from a whole blood sample from each subject. All of the coding exons of STK11 gene, its boundary regions, and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction, and direct sequencing was performed to assess the germline mutations. NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI polyps. Overall, we found 5 cases of type A and one case without the examination for the gastric polyps, while there were 4 cases of type B and 2 case of type A for the colorectal polyps. Seventy-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant complications. The only delayed complication included the occurrence of bleeding in a case, and this was successfully managed with hemoclips. Resected polyps contained no malignant components. Based on mutation analysis, all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5, which resulted in the production of a truncated protein (Q220X). In Family II, a case had -252C>A and -193C>A in the promoter region. In Family III, a case was found to have the +1062C>G (F342L) mutation in exon 8. We found two novel mutations of STK11 in association with PJS. Endoscopic polypectomy of GI polyps in PJS patients appears to be useful to prevent emergency laparotomies and reduce the cancer risk.
    Full-text · Article · Mar 2013
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    ABSTRACT: Malignant rhabdoid tumor is a rare tumor occurring mostly in the neonatal kidneys and central nervous system. Cutaneous malignant rhabdoid tumors are extremely rare in adults. The aim of the study was to report on the clinical, histologic, and immunophenotypic characteristics of this cutaneous malignant rhabdoid tumor which developed in an adult. A 27-yearold male complained of a right palm neoplasm that had been present for 6 months, which was initially diagnosed as an epithelioid sarcoma by biopsy. However, detailed investigation with immunohistochemistry enabled us to make a diagnosis of a rhabdoid tumor. The patient underwent radical abrasion, chemotherapy, and rradiation, and has survived for 1 year without relapse. Only 20 adult cases have been reported thus far in the English literature. We are reporting the 21st case, who remains disease-free at 12 months. Complete resection and local irradiation may increase survival, because there is no standard and reliable curative chemotherapeutic regimen.
    Full-text · Article · Jan 2013 · Rare tumors

Publication Stats

3k Citations
682.91 Total Impact Points

Institutions

  • 2002-2015
    • NHO Nagasaki Medical Center
      • Department of Neurosurgery
      Nagasaki, Nagasaki, Japan
  • 1995-2013
    • Nagasaki University
      • • School of Medicine
      • • Department of Pathology
      Nagasaki, Nagasaki, Japan
  • 1987-2013
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 2007
    • National Nuclear Center of the Republic of Kazakhstan
      Konechnaya, Pavlodar, Kazakhstan
  • 1986
    • University of Illinois, Urbana-Champaign
      • Department of Animal Sciences
      Urbana, Illinois, United States