Takeshi Ishii

Chiba Cancer Center, Tiba, Chiba, Japan

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Publications (38)141.41 Total impact

  • Cancer Research 08/2015; 75(15 Supplement):78-78. DOI:10.1158/1538-7445.AM2015-78 · 9.28 Impact Factor
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    ABSTRACT: In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma. This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513). A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS. The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    Cancer 07/2015; DOI:10.1002/cncr.29575 · 4.90 Impact Factor
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    ABSTRACT: Distant metastases from osteosarcoma most commonly occur in the lungs. Osteosarcoma can be cured by complete surgical resection of all metastatic lesions if the number is limited (oligo-recurrence: ≤5 metastatic or recurrent lesions with controlled primary lesions). This study aimed to clarify the prognostic factors for osteosarcoma patients with pulmonary metastasis and determine their oligo-recurrence status. Patients with conventional osteosarcoma who underwent definitive surgery for the primary lesion and at least one thoracotomy for pulmonary metastases were recruited to this retrospective study. Clinicopathological information was collected on each thoracotomy from 1976 to 2011, and was then analyzed statistically. We counted the number of resected nodules that were pathologically confirmed as metastatic lesions from osteosarcoma. In total, 151 thoracotomies in 71 patients were analyzed. Forty-seven patients (66 %) underwent up to two thoracotomies, and the maximum number of thoracotomies was six. The median number of resected nodules on each thoracotomy was two, and the median total size of metastatic lesions was 20 mm. Incomplete surgical remission [relative risk (RR) 3.42], a less than 1-year interval from a previous thoracotomy (RR 1.97), more than three resected nodules (RR 2.42); and total size of more than 30 mm for pulmonary metastases (RR 2.19) were independent predictors of increased risk of tumor death by multivariate analysis. We propose that factors contributing to oligo-recurrence of patients with pulmonary metastatic osteosarcoma include complete surgical remission, an interval from a previous thoracotomy, number of resected nodules, and total size of pulmonary metastases.
    Annals of Surgical Oncology 06/2015; DOI:10.1245/s10434-015-4682-1 · 3.94 Impact Factor
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    ABSTRACT: Epithelioid sarcoma (ES) is an extremely rare soft tissue sarcoma. Recently, the proximal variant has been reported to be a more aggressive subtype; however, as most reports of ES have involved small case series, the actual prognostic implications remain unclear. We investigated the clinicopathological features of patients with ES to identify the prognostic factors that influence survival. We retrospectively analyzed the clinicopathological features of 44 patients with ES who had been treated at our institutions between 1991 and 2011. Among these patients, 26 were diagnosed histologically as having classic-type ES, whereas the remaining 18 had proximal-type ES. Thirty-three of the patients, all without distant metastases, underwent curative surgery, and the remaining 11 with distant metastases (M1) received palliative treatment. The proximal subtype was significantly correlated with a proximal tumor location, distant metastases at presentation, presence of rhabdoid cells, a higher tumor grade, and vascular invasion. The overall survival (OS) rate at 5 years for the 44 patients was 45 %. A superficial tumor location and lymph node metastases (N1) at presentation were independently predictive of local recurrence-free survival (LRFS), and N1 and M1 tumors were independently predictive of distant metastasis-free survival and OS, respectively. The proximal subtype was associated with unfavorable LRFS and OS, although not to a statistically significant degree. Proximal-type ES has significantly more aggressive clinicopathological features than classic-type ES, and lymph node or distant metastasis has the most critical impact on prognosis.
    Annals of Surgical Oncology 02/2015; 22(8). DOI:10.1245/s10434-014-4294-1 · 3.94 Impact Factor
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    ABSTRACT: Background and Objectives Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS.Methods We reviewed 89 patients diagnosed with UPS or MFS and underwent initial surgery at our institute between 1994 and 2011. Growth patterns were assessed radiographically on preoperative MRI. Clinicopathological factors were collected and uni- and multivariate analyses were performed for survival.ResultsInfiltrative growth was observed in 21 patients (24%), which correlated with superficial tumors and positive surgical margin. Infiltrative growth correlated with poor disease-specific and distant failure-free survivals relative to non-infiltrative growth. Multivariate analysis confirmed that these factors remained as significant factors. Patients with non-infiltrative tumors resected inadequately exhibited slightly more favorable local control with postoperative radiotherapy, although no clinical benefit was seen for those with infiltrative tumors.Conclusions Infiltrative growth was an adverse prognostic factor for not only local control, but also disease-specific and metastasis-free survival in patients with UPS and MFS. Radiotherapy could not salvage inadequately resected infiltrative tumors. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 11/2014; 110(6). DOI:10.1002/jso.23708 · 2.84 Impact Factor
  • Cancer Research 10/2014; 74(20 Supplement):A49-A49. DOI:10.1158/1538-7445.PEDCAN-A49 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3102-3102. DOI:10.1158/1538-7445.AM2014-3102 · 9.28 Impact Factor
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    ABSTRACT: Background Osteosarcoma as second malignancy of childhood cancers rarely occurs, and its clinical characteristics are unclear. Methods Patients with osteosarcoma occurring as second malignancy of childhood cancers were retrospectively surveyed. Results Of 323 patients with osteosarcoma registered in the database, 10 (3.1 %) had a past history of childhood cancers. The mean age at the onset of the first childhood cancer was 2.7 years, and the diagnosis of the first childhood cancer was adrenocortical carcinoma, malignant teratoma, ovarian carcinoma, Ewing’s sarcoma, and rhabdomyosarcoma in 1 patient each, and retinoblastoma in 5 patients. Osteosarcoma as second malignancy occurred 14.6 years after the first childhood cancer on average. Seven patients were alive and 3 died. In 1 patient, the cause of death was related to a complication of treatment for the first childhood cancer. Except for this patient, 7 (77.8 %) of 9 patients survived with no disease (mean follow-up period: 10.9 years). Conclusions Attention should be paid to complications of treatment for the first childhood cancer in the treatment for osteosarcoma occurring as second malignancy. The prognosis of osteosarcoma as second malignancy of childhood cancers may be more favorable than that of conventional osteosarcoma.
    International Journal of Clinical Oncology 07/2014; 20(3). DOI:10.1007/s10147-014-0729-8 · 2.17 Impact Factor
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    ABSTRACT: IntroductionFibrous dysplasia (FD) is a benign medullary fibro-osseous lesion that may present as monostotic or polyostotic. Bone deformities often manifest in polyostotic FD, especially in the femoral neck region, due to repeated microfractures. The deformity observed in the proximal femur has been referred to as shepherd’s crook deformity and is characterized by coxa vara. This deformity causes shortening of the affected limb, limited range of motion (ROM) of the hip joint, and a reduction in the gluteus medius muscle, resulting in the marked aggravation of function in the affected limb [1, 2]. Surgical treatment for FD should be performed when a pathological fracture occurs or serious symptoms develop due to the deformity; however, correcting shepherd’s crook deformity to obtain a desirable mechanical axis and lengthening the lower limb is challenging [2-6]. Furthermore, weight bearing is restricted for a long period until both treated femora obtain sufficient bony union. We report ...
    Journal of Orthopaedic Science 09/2013; 20(2). DOI:10.1007/s00776-013-0463-5 · 1.01 Impact Factor
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    ABSTRACT: The occurrence of osteosarcoma in elderly patients has recently been increasing, and the outcome is poor. This multi-institutional retrospective study was conducted to investigate clinical features and prognostic factors in patients older than 40 years with osteosarcoma. Patients with conventional high-grade osteosarcoma older than 40 years were recruited to this study. Secondary osteosarcoma arising from Paget's disease or irradiated bones was excluded. Information on tumor- and treatment-related factors was collected and statistically analyzed. The median follow-up was 57 months (range 8-244 months) for all surviving patients. A total of 86 patients were enrolled in this study. The median age at diagnosis was 61 years. Surgery and chemotherapy were conducted in 73 and 63 % of all patients, respectively. The 5-year overall and event-free survival rates were 38.8 and 34.0 %, respectively. Tumor site (extremity 57.9 %; axial 19.0 %; p < 0.0001), metastasis at diagnosis (yes 12.2 %; no 48.3 %; p < 0.0091), and definitive surgery (yes 56.2 %; no 10.6 %; p < 0.0001) were associated with overall survival. Although patients without metastasis who received definitive surgery were regarded as good candidates for chemotherapy, the addition of chemotherapy did not have any impact on the outcome (yes 63.4 %; no 65.2 %; p = 0.511). The present study revealed the distinct clinical features, such as the high incidence of truncal tumors or metastasis at diagnosis, in patients older than 40 years with osteosarcoma. Additionally, prognostic factor analyses revealed that tumor site, metastasis at diagnosis, definitive surgery, and surgical margins were significant prognostic factors, whereas chemotherapy did not influence survival.
    Annals of Surgical Oncology 08/2013; 21(1). DOI:10.1245/s10434-013-3210-4 · 3.94 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):3815-3815. DOI:10.1158/1538-7445.AM2013-3815 · 9.28 Impact Factor
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    ABSTRACT: BACKGROUND: Treatment for unresectable Ewing's sarcoma family of tumors (ESFT) is a formidable challenge because of its high tendency for local and distant failure. Recently, carbon-ion radiotherapy (CIRT) has been applied to unresectable bone and soft tissue sarcoma. Additionally, high-dose chemotherapy (HDC) with stem cell rescue has been used to improve the survival of patients with relapsed ESFT. Here we report our experience with CIRT and HDC in the treatment of unresectable ESFT. METHODS: Five unresectable ESFT patients including 4 who underwent CIRT and HDC and one who underwent CIRT from 1999-2009 were retrospectively studied. After neoadjuvant chemotherapy, CIRT was conducted at the National Institute of Radiological Sciences in Chiba as local therapy. Consecutively, we employed HDC including busulfan, melphalan, and thiotepa with stem cell rescue. RESULTS: Two patients showed tumor shrinkage after CIRT, including 1 patient who achieved partial response. No severe acute toxicity related to CIRT was observed. Local failure was observed in only 1 patient at 22 months after CIRT. Four patients conducted HDC with stem cell rescue after CIRT and 1 patient suffered from veno-occlusive disease just after HDC. Distant failure was observed in 3 patients after completion of the treatment. CONCLUSIONS: CIRT and HDC for unresectable ESFT patients show favorable local control, with unsatisfactory results for distant control.
    International Journal of Clinical Oncology 10/2012; 18(6). DOI:10.1007/s10147-012-0480-y · 2.17 Impact Factor
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    ABSTRACT: In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.
    Cancer Science 06/2012; 103(9):1625-30. DOI:10.1111/j.1349-7006.2012.02370.x · 3.53 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):5579-5579. DOI:10.1158/1538-7445.AM2012-5579 · 9.28 Impact Factor
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    ABSTRACT: Posttraumatic stress symptom (PTSS) and posttraumatic growth (PTG) were surveyed in parents of childhood, adolescent and young adult patients with high-grade osteosarcoma. A questionnaire survey was performed in parents of patients with osteosarcoma (51 families). The Impact of Event Scale-Revised (IES-R) and posttraumatic growth inventory (PTGI) were employed for the evaluation of PTSS and PTG, respectively. The mean scores were compared with those in preceding studies employing the same scales. In addition, the correlation between the IES-R and PTGI scores was investigated in the parents. Fifty-eight subjects of 34 families (30 fathers and 28 mothers) replied to the questionnaire. The mean IES-R score in the parents was 18.5, which was higher than that in patients with osteosarcoma (9.7) in our previous study. The mean PTGI score in the parents was 44.9, which was higher than that in university students (33.9) reported by Taku et al. A positive correlation was noted between the IES-R and PTGI scores in the parents. The PTSS level tended to be higher in the parents rather than in patients with osteosarcoma. The PTG level increased as the PTSS level rose in the parents.
    International Journal of Clinical Oncology 07/2011; 17(3):272-5. DOI:10.1007/s10147-011-0286-3 · 2.17 Impact Factor
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    ABSTRACT: Imatinib myselate is a molecularly targeted drug that inhibits Abl tyrosine kinase, as well as type III tyrosine kinase receptors such as platelet-derived growth factor receptor (PDGFR), KIT, colony-stimulating factor 1 receptor (CSF-1R), and discoidin domain receptor (DDR). Ph1 chromosome-positive chronic myeloid leukemias (CMLs), KIT-positive gastrointestinal stromal tumors (GISTs), and PDGFR-positive dermatofibrosarcoma protuberans (DFSP) have been reported to be responsive to imatinib treatment. We conducted a multicenter Phase II trial of imatinib in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Patient ages ranged from 12 and 75 years. Eligibility criteria included (1) metastatic sarcomas with a definitive diagnosis based on histopathology or that were completely unresectable and locally advanced; (2) relapsed or refractory cases that had completed standard treatment; and (3) a tumor confirmed by immunohistochemical staining to be KIT- or PDGFR-positive. A 600-mg dose of imatinib was administered to patients once a day, with each patient receiving six courses of the drug and each course lasting 4 weeks. In cases categorized as stable or progressive, the imatinib dose was increased to 800 mg/day administered twice daily. A total of 25 patients who met the eligibility criteria were enrolled in the trial; 22 were evaluated for response. The response rate with a 600 mg/day dose of imatinib was 4.5% (0 complete response, 1 partial response). There were no other objective responses after increasing imatinib to 800 mg/day (0/10). We estimated 50% progression-free survival to be 61.0 days for an imatinib dose of 600 mg/day based on the Kaplan-Meier method. Side effects of imatinib were generally similar to those observed in previous clinical trials. Our results did not indicate effectiveness of imatinib monotherapy at a dose of 600 or 800 mg/day in patients with relapsed or refractory KIT-positive (excluding GISTs) or PDGFR-positive sarcomas. Our findings suggest the need to evaluate the synergistic effect of combination therapy with other anticancer drugs.
    Journal of Orthopaedic Science 09/2010; 15(5):654-60. DOI:10.1007/s00776-010-1506-9 · 1.01 Impact Factor
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    ABSTRACT: Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real-time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3-expressing patients had significantly worse overall survival. Relative PHC3 values of clinical samples were less than those of normal bone tissues, whereas they were greater than those of cell lines. By denaturing high performance liquid chromatography analysis and direct sequencing, we found a PHC3 missense mutation in U2OS cells, which resulted in arginine56 to proline substitution. The same point mutation existed in four of 42 primary osteosarcoma samples. Regarding functional analysis, PHC3 expression significantly suppressed the colony formation of tumor cells. Intriguingly, polycomb repressive complex 1 members, Bmi1 and Ring1b proteins, were reduced in PHC3-expressing osteosarcoma cells. Deletion mutant PHC3 expression suggested that the carboxyl terminus of PHC3 has a role in suppression; the above-mentioned point mutation of PHC3 also lost inhibitory activities. Conversely, Bmi1 expression reduced PHC3 at the mRNA level and induced the proliferation of osteosarcoma cells. Taken together, we confirmed the role of PHC3 as a tumor suppressor in osteosarcoma cells and found that PHC3-dependent tumor suppression may be caused by modification of the composition of polycomb repressive complex 1 in cancer cells.
    Cancer Science 07/2010; 101(7):1646-52. DOI:10.1111/j.1349-7006.2010.01586.x · 3.53 Impact Factor
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    ABSTRACT: The psychosocial outcomes in long-term survivors of osteosarcoma were investigated. A questionnaire concerning the psychosocial status was completed by 30 long-term survivors of osteosarcoma. The family APGAR was employed for the evaluation of family function, social support questionnaire (SSQ) for social support, impact of event scale-revised (IES-R) for posttraumatic stress symptoms (PTSS), and posttraumatic growth inventory (PTGI) for posttraumatic growth (PTG). The family APGAR and SSQ scores were comparable to those of controls. The IES-R score was low, showing a low incidence of PTSS. The PTGI score was high, revealing marked PTG. On multiple regression analysis regarding the IES-R as a dependent variable, the family APGAR was associated with the IES-R. On multiple regression analysis regarding the PTGI as a dependent variable, the age at diagnosis, state of the affected limb and SSQ were associated with the PTGI. The incidence of PTSS was low, and PTG was marked in the long-term survivors of osteosarcoma. A high age at onset and amputation of the affected limb were associated with PTG. Support of the family function reduces PTSS, and the strengthening of social support facilitates PTG.
    Anticancer research 10/2009; 29(10):4287-90. · 1.87 Impact Factor
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    ABSTRACT: Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out. To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible. The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy. We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.
    Journal of Orthopaedic Science 08/2009; 14(4):397-404. DOI:10.1007/s00776-009-1347-6 · 1.01 Impact Factor
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    ABSTRACT: To investigate the marital status and fertility in long-term survivors of high-grade osteosarcoma. We surveyed the marital rate (number of married persons/total number of persons) in 46 long-term survivors of osteosarcoma who were treated in our hospital between 1976 and 2002. In addition, we examined the fertility rate (number of persons having offspring/number of married persons) in 29 married patients. The participants were divided into 2 groups: one group (MC) in which moderate-dose chemotherapy was performed between 1976 and 1986; and another group (IC) in which intensive-dose chemotherapy was performed between 1987 and 2002. In each group, the fertility rate was investigated. As controls, we surveyed the marital and fertility rates in 52 siblings of the patients. In the patients, the marital rate was 63.0% (29/46). There was no significant difference in the marital rate between the patients and their siblings. In the patients, the overall fertility rate was 58.6% (17/29). The fertility rate of male patients in the IC group (16.7%, 1/6) was significantly lower than that of their male siblings (76.5%, 13/17) (p = 0.018). These results suggest that recently intensified chemotherapy for osteosarcoma affects fertility in long-term male survivors.
    Anticancer research 03/2009; 29(2):763-7. · 1.87 Impact Factor

Publication Stats

439 Citations
141.41 Total Impact Points


  • 1999–2015
    • Chiba Cancer Center
      Tiba, Chiba, Japan
  • 2013
    • Tokyo Women's Medical University
      Edo, Tōkyō, Japan
  • 2002–2004
    • Sapporo Medical University
      • Division of Orthopaedic Surgery
      Sapporo, Hokkaidō, Japan