Toshiharu Yasugi

Tokyo Metropolitan Cancer and Infectious Diseases Center, Edo, Tokyo, Japan

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Publications (111)365.97 Total impact

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    ABSTRACT: Background: Although many studies have already shown that lymph node metastasis is one of the major prognostic factors for cervical cancer, the therapeutic significance of para-aortic lymphadenectomy for the surgical treatment of cervical cancer remains controversial. Methods: A total of 308 patients diagnosed with stage IB2, IIA2, or IIB cervical cancer and treated with radical hysterectomy were retrospectively investigated to assess the incidence of para-aortic lymph node metastasis and the clinicopathological factors linked to cervical cancer prognosis. Results: Para-aortic lymph node metastases were pathologically confirmed in 13 of the 136 patients (9.6 %) who underwent para-aortic lymphadenectomy. The incidence of para-aortic lymph node metastasis was significantly higher in the patients who had common iliac lymph node metastases (odds ratio 31.5, p < 0.001) according to logistic regression analysis. Common iliac lymph node metastasis was related to risk of recurrence (hazard ratio 2.43, p = 0.003) and death (hazard ratio 2.62, p = 0.007) in Cox regression analysis. Kaplan-Meier analysis and Cox regression analysis showed that para-aortic lymphadenectomy did not have a positive impact on survival in 308 patients or 140 pN1 patients, but para-aortic lymphadenectomy was related to better overall survival with a marginal trend toward significance (p = 0.053) in 30 patients with common iliac lymph node metastasis. Conclusions: Indication for para-aortic lymphadenectomy in the surgical treatment of stage IB2, IIA2, or IIB cervical cancer needs to be individualized. Patients with common iliac lymph node metastasis are possible candidates, and a prospective study is needed to clarify this issue.
    Full-text · Article · Oct 2015 · International Journal of Clinical Oncology
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    ABSTRACT: We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n=341), cervical intraepithelial neoplasia grade 1 (CIN1, n=505), CIN grade 2 or 3 (CIN2/3, n=96) or invasive cervical cancer (ICC, n=311). HLA class II allele frequencies were compared by Fisher's exact test or the χ2 test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion (LSIL) cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA Class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P=0.0003). Correction for multiple testing did not change this finding. In women with LSIL cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P=0.03). In conclusion, the two different types of analysis in this single study demonstrated the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Aug 2015 · Cancer Science
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    ABSTRACT: We describe 9 tumors that resemble soft tissue myoepitheliomas but possess certain traits that do not fit perfectly into this category. These tumors, herein referred to as "myoepithelioma-like tumors of the vulvar region," occurred in the subcutis of the vulva and surrounding regions of adult women aged 24 to 65 years. Histologically, the tumors measured 2 to 7.7 cm and were well circumscribed, focally encapsulated, and lobulated. Tumor cells had an epithelioid to spindled shape, with fine amphophilic cytoplasm, and uniform nuclei with vesicular chromatin and nucleoli. The tumor stroma was relatively hypervascular, and comprised a mixture of myxoid and nonmyxoid components. Myxoid areas accounted for <5% to 95% of the tumor volume, wherein cells proliferated singly or in a loosely cohesive manner. In nonmyxoid areas, tumors cells grew in diffuse sheets or storiform arrangements. Immunohistochemically, all tested tumors were positive for vimentin, epithelial membrane antigen, and estrogen receptor; most tumors expressed actin. All tumors were negative for S100 protein, glial fibrillary acidic protein, and CD34. Cytokeratin expression was absent in all but 2 tumors, which showed rare positivity. SMARCB1 expression was deficient in all cases. EWSR1, FUS, and NR4A3 rearrangements were absent. All tumors were treated through surgery. Although 3 tumors regrew or recurred after intralesional excision, all 9 patients were alive without metastases at a mean follow-up of 66 months. Myoepithelioma-like tumors of the vulvar region constitute a distinct group of tumors, although future research is required to determine whether they are an unusual subtype of soft tissue myoepitheliomas or a separate disease.
    No preview · Article · Aug 2015 · The American journal of surgical pathology
  • A. Furusawa · M. Uno · M. Mori · N. Kino · Y. Ozaki · T. Kubota · T. Yasugi

    No preview · Article · Nov 2014 · International Journal of Gynecological Cancer
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    ABSTRACT: Few reports on malignant transformation of adenomyosis are available, and endometrioid adenocarcinoma arising from cystic adenomyosis is further rarely reported. We report a case of a 67-year-old asymptomatic woman who was referred to our hospital for evaluation of a cystic lesion in the pelvis, which had been diagnosed as cystic degeneration of leiomyoma for 3 years. Magnetic resonance imaging revealed a cystic mass measuring 11 cm in diameter, which was contiguous with uterine myometrium. The lesion contained solid areas enhanced on gadolinium-enhanced T1 -weighted imaging. Transabdominal simple total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination revealed endometrioid adenocarcinoma arising from cystic adenomyosis. The patient underwent six courses of adjuvant combination chemotherapy with paclitaxel and carboplatin. No metastasis or recurrence has been demonstrated for 16 months following surgery. Our case demonstrates that cystic adenomyoma possesses the risk of malignant transformation, indicating the importance of long-term follow-up with imaging examination.
    No preview · Article · Oct 2014 · Journal of Obstetrics and Gynaecology Research
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    ABSTRACT: Patients with advanced uterine cervical cancer are sometimes treated with extended field radiotherapy (EFRT). We evaluate morbidity and outcome of patients who were treated with EFRT. We evaluated patients newly diagnosed as cervical cancer and treated with EFRT after 2005. Forty patients are eligible, 16 of them were para-aortic node (PAN) positive, grade 3 or worse adverse events were observed in 9 patients, and 6 of them occur in pelvis. Two year disease-free-survival for PAN positive patients is 59.0%. The risk of adverse events was acceptable. Patients with positive PAN can be candidate for intensive treatment.
    No preview · Article · Oct 2014
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    ABSTRACT: This is a retrospective study of fifteen cases of primary peritoneal carcinoma who were treated between 2001 and 2010 in our hospital. The median age at the time of diagnosis was 63 years(range, 40 to 79 years). Three patients had clinical stage II disease, eleven patients had stage III disease, and one patient was unstaged. The serum CA125 values at pretreatment were elevated in all patients, with a median value of 4,144. 8 U/mL(range, 102. 8 to 23, 611. 0 U/mL). Optimal debulking was possible in 9 of the 15 patients. All patients were treated with paclitaxel and carboplatin chemotherapy during the preoperative and/or postoperative period. All patients at stage II disease were alive without evidence of disease at the time of evaluation(2 patients>5 years, 1 patient>3 years). Four patients with stage III disease had died from the disease less than 3 years after the first treatment. The results of our study showed poor survival for the group with stage III disease, but good survival for the group with stage II disease.
    No preview · Article · Jul 2013 · Gan to kagaku ryoho. Cancer & chemotherapy
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    ABSTRACT: Background: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. Methods: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1–5, vincristine 0.7 mg m−2 day 5, mitomycin 7 mg m−2 day 5, cisplatin 14 mg m−2 days 1–5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. Results: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80% P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). Conclusion: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.
    Full-text · Article · May 2013 · British Journal of Cancer

  • No preview · Article · Jan 2013 · Open Journal of Obstetrics and Gynecology
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    ABSTRACT: Background: It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities. Methods: In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1-2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status. Results: In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78-2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11-0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24-1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97-5.42, p = 0.058). Conclusions: Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.
    No preview · Article · Oct 2012 · International Journal of Clinical Oncology
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    ABSTRACT: To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low-grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16-specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16-specific neutralizing antibodies (P = 0.03, log-rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low-grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression.
    No preview · Article · Jul 2012 · Journal of Medical Virology
  • Toshiharu Yasugi

    No preview · Article · Jun 2012 · Nippon rinsho. Japanese journal of clinical medicine

  • No preview · Article · May 2012 · Radiotherapy and Oncology
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    ABSTRACT: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.
    No preview · Article · Mar 2012 · International Journal of Gynecological Cancer
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    ABSTRACT: Uterine leiomyoma are very common benign tumors in women of reproductive age. However, the molecular mechanisms of cause and development of these tumors are poorly understood. This study attempts to examine whether or not aberrant DNA methylation occurred in these tumors. We carried out a genome-wide screen for aberrant DNA methylation, adopting methylation-sensitive-representational difference analysis (MS-RDA) using normal adjacent myometria as tester and myoma tissue driver. A total of 192 clones identified by MS-RDA were sequenced, 27 DNA fragments derived from CpG islands (CGIs) were isolated, and seven of them were from CGI in the 5' regions of known genes, which include CHARC1, FAM44B, FLJ33655, HSUP, MLLT3, SLC16A1, and ZNF96. Then, methylation statuses of those CGIs were analyzed by methylation-specific polymerase chain reaction using 5 primary samples of human uterine leiomyoma. Aberrant DNA methylation did not observed in 7 genes in 5 human uterine leiomyoma eventually. This study is insufficient to identify aberrant DNA methylation occurring in the human uterine leiomyoma, a large population of primary samples and more attempts, such as the use of cell lines or primary monolayer cultures established from tissue samples, are warranted to clarify this issue.
    Full-text · Article · Sep 2011 · The Tokai journal of experimental and clinical medicine
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    ABSTRACT: To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy. In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy. In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73). In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.
    No preview · Article · Jul 2011 · International Journal of Clinical Oncology
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    ABSTRACT: To evaluate the usefulness of intraoperative ultrasonography (IU) in reducing the number of unnecessary para-aortic lymphadenectomy in women with endometrial carcinoma. Computed tomography (CT) and IU were used to assess whether para-aortic lymph nodes were enlarged in 91 women with endometrial carcinoma. All women underwent hysterectomy and systematic pelvic and para-aortic lymphadenectomy. On the basis of the intrauterine pathological findings (IPF) of the removed uterus, the women were classified into low- and high-risk groups. It was assumed that para-aortic lymphadenectomy would be performed only when enlarged nodes were detected by CT or IU or only when women were classified into the high-risk group. The numbers of women who would have had missed metastases and who could have avoided para-aortic lymphadenectomy were calculated. Eighteen women had pathological para-aortic node metastases. Theoretically, the number of women who would have had missed metastases on the basis of CT, IU, and IPF were 11, 2, and 2, respectively; more metastases were missed with CT than with the other 2 methods. The number of women who could have avoided para-aortic lymphadenectomy on the basis of CT, IU, and IPF were 84, 59, and 29, respectively; compared to IPF, IU helped avoid para-aortic lymphadenectomy in more women. Intraoperative ultrasonography is the most efficient method for avoiding both unnecessary para-aortic lymphadenectomy and missed para-aortic node metastases in women with endometrial carcinoma.
    No preview · Article · Jul 2011 · International Journal of Gynecological Cancer
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    ABSTRACT: Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.
    Full-text · Article · Jun 2011 · International Journal of Cancer
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    ABSTRACT: We retrospectively evaluated the efficacy and toxicity of docetaxel and carboplatin in patients with platinum and paclitaxel-pretreated recurrent ovarian, fallopian tube, and peritoneal cancer. Forty-two women (38 with ovarian cancer, 1 with fallopian tube cancer, 3 with peritoneal cancer) whose cancer had progressed within 12 months of their last treatment with both a platinum agent and paclitaxel were treated with docetaxel (70 mg/m(2), day 1) and carboplatin (area under the curve of 4-6, day 1). Thirty-four patients had measurable disease. The objective response rate was 23% within 0-6 months of the progression-free interval, 50% within 6-12 months, and 32% (11 of 34 patients) for both groups. The median time to tumor progression was 28, 49, 34 weeks, and the median overall survival time was 94, 224, 111 weeks, respectively. The most common toxicity was grade 3/4 neutropenia (98% of patients), with 15 episodes (8.4% of courses) of neutropenic fever. The main nonhematologic toxicity was hypersensitivity; 7 patients (17%) required discontinuation of the therapy. The results of our study indicate that the combination of docetaxel and carboplatin is effective against recurrent ovarian, fallopian tube, and peritoneal cancer with progression-free interval of 6-12 months from previous treatment by paclitaxel and platinum. On the other hand, single-agent chemotherapy would be better than this regimen considering its low response rate and severe hematological toxicity for patients with progression-free interval less than 6 months.
    No preview · Article · Mar 2011 · Medical Oncology
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    ABSTRACT: Ovarian clear cell adenocarcinoma (OCCA) is known to have a worse prognosis than ovarian serous adenocarcinoma due to its poor response to conventional platinum-based chemotherapy. Idiopathic thrombocytopenic purpura (ITP), which usually reveals severe thrombocytopenia, is a common autoimmune disorder. However, to date very few cases of ovarian cancer associated with ITP have been reported in the literature. We report a case of a 57-year-old woman who developed OCCA 14 years after the diagnosis of ITP. The patient presented with abdominal distention and mild tenderness. We performed the operation with high-dose immunoglobulin therapy preoperatively, and diagnosed OCCA. Postoperatively, six cycles of cytotoxic chemotherapy with irinotecan hydrochloride plus cisplatin were performed every 4-5 weeks without thrombocytopenia. We conclude that combination chemotherapy with irinotecan hydrochloride plus cisplatin is useful for a case of OCCA associated with ITP.
    No preview · Article · Dec 2010 · International Journal of Clinical Oncology

Publication Stats

3k Citations
365.97 Total Impact Points

Institutions

  • 2010-2015
    • Tokyo Metropolitan Cancer and Infectious Diseases Center
      Edo, Tokyo, Japan
  • 2009-2015
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tokyo, Japan
  • 1996-2015
    • The University of Tokyo
      • Department of Obstetrics and Gynecology
      白山, Tōkyō, Japan
  • 2008
    • Harvard Medical School
      • Department of Obstetrics, Gynecology, and Reproductive Biology
      Boston, Massachusetts, United States
  • 2007
    • Kurume University
      • Department of Obstetrics and Gynecology
      Куруме, Fukuoka, Japan
  • 2005
    • Tokyo Medical University
      • Department of Obstetrics and Gynecology
      Edo, Tōkyō, Japan
  • 1988-1990
    • Nihon University
      • School of Medicine
      Edo, Tokyo, Japan
  • 1984
    • Kanazawa Medical University
      Kanazawa, Ishikawa, Japan