Takeshi Morii

Kyorin University, Edo, Tokyo, Japan

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Publications (47)74.99 Total impact

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    ABSTRACT: Background/Aim: Plasma D-dimer levels have been known to be associated with tumor progression; we, therefore, investigated whether the D-dimer levels during preoperative systemic chemotherapy can be prognostic indicators in patients with high-grade musculoskeletal sarcoma. Patients and Methods: We investigated 28 cases of high-grade sarcomas, and evaluated the utility of D-dimer levels for preoperative evaluation of the effects of systemic chemotherapy. Results: Among the candidate parameters determined based on D-dimer levels at several time-points of neoadjuvant chemotherapy and several oncological outcomes, the plasma D-dimer level completion of the second course of chemotherapy and the ratio of plasma D-dimer levels at completion of preoperative chemotherapy to the level of plasma D-dimer on referral, could significantly predict patient prognosis (p=0.049 and p=0.02, respectively). Conclusion: D-dimer level changes could be a helpful marker for preoperative evaluation of the effect of systemic chemotherapy in terms of prognosis prediction in high-grade musculoskeletal sarcoma patients.
    No preview · Article · Dec 2015 · Anticancer research
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    ABSTRACT: Although systemic chemotherapy is inevitably selected as the modality of treatment for high-grade bone and soft tissue sarcoma (BSTS), limited information is available regarding febrile neutropenia (FN). FN incidence, blood culture results and risk factors were analyzed in 35 patients with high-grade BSTS. FN occurred in 51% of the patients and 24% of the courses of systemic chemotherapy. Culture results indicated pathogen in only 33.3% of patients who had FN. Methicillin-resistant Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus were frequently observed. Body weight of less than 61.0 kg and a tumor originating from the bone in a patient-based analysis, and serum albumin <4.2 g/dl and having a source of infection in a course-based analysis were independent risk factors for FN. Considerably high risks for FN during chemotherapy for BSTS were confirmed. The risk factors presented here appeared to differ from those in previously reported guidelines. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    No preview · Article · Apr 2015 · Anticancer research
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    ABSTRACT: Over the past three decades, several studies have reported worse outcomes with unplanned resection for malignant soft tissue tumors. However, the impact of these studies on preventing unnecessary unplanned resection remains unknown. In a retrospective survey on the treatment of soft tissue sarcomas, we compared cases of unplanned resection with cases of planned resection in terms of the properties of unplanned resection and the oncological and functional outcomes. For the unplanned resection cases, an additional wide resection was performed. Of 92 cases, unplanned resection was performed in 24 (26 %). Small or subcutaneous tumors were significantly more frequently subjected to unplanned resection. In 17 of 24 unplanned resection cases, residual tumors (70.8 %) were noted. Plastic surgery was more frequently needed for unplanned resection cases. There was no significant difference between the unplanned resection and control cases with regard to oncological outcome. However, as to local recurrence and overall survival, the events occurred only in the cases with residual tumors in the additional wide resection specimen in the unplanned resection group. There was no significant difference in functional evaluation, except for emotional acceptance, which had a better score in the unplanned resection group. Despite repeated cautions regarding unplanned resection in terms of its inadequate procedure which contradicts the principles of soft tissue sarcoma treatment, unplanned resections are still frequently performed. Perhaps the small size and subcutaneous location of the sarcomas in the unplanned resection group did not evoke the probability of malignancy for the surgeons who initially managed them. Even though an additional wide resection was performed, a residual tumor would lead to a worse outcome. An effective awareness program to avoid unnecessary unplanned resections for soft tissue sarcoma should be considered.
    No preview · Article · Jan 2015 · Journal of Orthopaedic Science
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    ABSTRACT: Background: Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells. Materials and methods: Chondrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bcl-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer (Bak). In vitro growth inhibition by BH-3 mimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELISA). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. Results: Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcoma growth and improved survival in a mouse model. Conclusion: BH3 mimetics represent a novel treatment modality for chondrosarcoma.
    No preview · Article · Nov 2014 · Anticancer research
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    ABSTRACT: Background: Lipoma and well-differentiated liposarcoma (WDLS) are two representative lipogenic soft tissue tumors that have similar clinical, radiological, and pathological characteristics. Accordingly, it is difficult to distinguish these tumors preoperatively. Plasma D-dimer levels are associated with the status of tumor progression, and we hypothesized that D-dimer levels could contribute to differential diagnosis. The D-dimer levels of these two entities have not yet been reported. Patients and methods: We investigated 43 cases of lipoma and 14 cases of WDLS. We evaluated the utility of D-dimer levels and other clinicopathological factors for preoperative differential diagnosis between the two entities. Results: Receiver operating characteristic analysis revealed that the D-dimer level may contribute to differential diagnosis (area under the curve=0.73). Univariate and multivariate models demonstrated that plasma D-dimer levels (p=0.001 (univariate), and p=0.006 (multivariate)) and lower extremity location (p=0.006 (univariate), and p=0.03 (multivariate)) were independent risk factors for WDLS. Conclusion: The D-dimer level may be a helpful marker for preoperative differential diagnosis between lipoma and WDLS.
    No preview · Article · Sep 2014 · Anticancer research
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    ABSTRACT: Introduction: We previously demonstrated that a family predisposed to lung cancer harbored a V843I substitution in the epidermal growth factor receptor (EGFR) protein. We report here the further characterization of this mutant EGFR protein in the context of tumorigenicity and resistance to tyrosine kinase inhibitors (TKIs) of EGFR activity. Methods: Phosphorylation of EGFR and downstream signaling proteins of lung adenocarcinoma cell lines with EGFR mutations was assayed by flow cytometry. Susceptibility to TKIs of these cell lines, with or without suppression of mutant EGFR expression by small inhibitory RNA (siRNA), was investigated using a cellular viability assay. Furthermore, protein modeling was used to predict TKI binding to EGFR protein carrying the V843I mutation. Results: Phosphorylation of EGFR and downstream signaling proteins was elevated upon transfection with an EGFR gene with the V843I. Although the cell line with V843I + L858R demonstrated resistance to EGFR-TKIs, the cells became susceptible to TKIs upon incubation with siRNA specific for the V843I allele. The structural analysis suggested that TKI binding to EGFR would be sterically hindered by Arg841 in the double-mutant (V843I + L858R) EGFR. Conclusions: The V843I mutation contributes to tumorigenesis by promoting phosphorylation of EGFR and its downstream signaling proteins. This mutation also appears to provide resistance to EGFR-TKIs through structural modification of EGFR. These features are comparable with those in EGFR T790M mutation, suggesting that cases with germ-line V843I or T790M mutations could be categorized as a class of familial lung cancer syndrome with resistance to EGFR-TKIs.
    No preview · Article · Jul 2014 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear. Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance. Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance. Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.
    No preview · Article · Dec 2013 · Anticancer research
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    ABSTRACT: Background: Although intensive studies have been conducted to clarify the incidence, risks, and management methods of deep infection of tumor endoprostheses, limited data have been published in respect of the impact of such deep infection on the function of the corresponding limb. Methods: Clinical data of 125 patients (infection group 57, control group 68) with malignant bone and soft tissue tumors around the knee enrolled with the Japanese Musculoskeletal Oncology Group were collected. We analyzed the impact of deep infection of tumor endoprostheses on the limb salvage status together with that on the function of the salvaged limb. The definition of deep infection was based on the recommendations of the Centers for Disease Control and Prevention. The functional evaluation was based on the functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society. Results: Infection together with extracapsular resection was demonstrated to be a risk factor for late amputation. There were no significant differences in the functional scores for "pain," "support," "walking," or "gait" between the infection and control groups. The risk factors identified for a loss of score for "functional activities" were deep infection, age, duration of operation, and extracapsular resection. The infection group also showed a significant lower score loss in "emotion". As for the overall functional scores, the risk factors identified for lower scores were deep infection and age. The mean scores for the infection group and control group were 19.3 (64.3 %) and 21.6 (72 %), respectively. Although the difference was confirmed to be statistically significant, the actual difference was only 2.3 (10.6 % reduction). Conclusions: Infection was a major risk factor for late amputation. Limbs salvaged by management of deep infection may show loss of function; however, the impact may be limited.
    No preview · Article · Apr 2013 · Journal of Orthopaedic Science
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    ABSTRACT: Background The incidence of endoprosthesis failure has been well studied, but few studies have described the clinical characteristics of deep infection in tumor prostheses. This study aimed to analyze the characteristics of deep infection in tumor endoprostheses around the knee. Methods We analyzed clinical data of 57 patients with deep infections involving tumor endoprostheses around the knee enrolled from the Japanese Musculoskeletal Oncology Group. Profile of clinical presentation including time between surgery and infection, initial symptoms/blood tests and microbial cultures was evaluated. In addition pre-, intra-, and postoperative clinical factors influencing clinical presentation and treatment outcomes of infections were analyzed. Results Mean interval between the initial operation and diagnosis was 13 months, and mean time required for infection control was 12 months. The most common pathogen was Staphylococcus. Infection control rates were significantly higher when prostheses were removed rather than salvaged. Ten-year prosthesis survival and limb salvage rates were 41.6% and 75.6%, respectively. Analysis of underlying clinical factors suggested that soft-tissue condition significantly influenced the duration of the infection control period and likelihood of limb salvage. Conclusions Infection control is a prolonged process. Deep infection frequently results in amputation or prosthesis loss. Intensive analysis of clinical characteristics may aid infection control.
    Preview · Article · Jan 2013 · BMC Musculoskeletal Disorders
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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.
    No preview · Article · Jun 2012 · Cancer Science
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    Preview · Article · Apr 2012 · Journal of Orthopaedic Science
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    ABSTRACT: Postoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk. This series comprised 84 patients with malignant soft tissue tumors treated at our institute. The occurrence rate, management modality and clinical course of surgical site infections, impact of surgical site infections on the length of hospitalization, risk factors for the development of surgical site infections, and the impact of surgical site infections on the oncological outcomes were analyzed. Surgical site infection was defined according to Centers for Disease Control and Prevention guidelines. Surgical site infections occurred in 7 cases (8.3%). Although successful clinical cure was achieved in all cases, surgical site infection was identified as one of the independent risk factors for prolongation of hospitalization. Both univariate and multivariate analyses identified larger intraoperative blood loss and a trunk location as risk factors associated with deep infections. No association was detected between age, tumor grade, chemotherapy, tumor volume, or plastic surgery and the risk of surgical site infections. Although the differences were not statistically significant, patients with surgical site infections showed worse oncological outcomes in terms of local recurrence and total survival. The incidence rate of surgical site infection was larger than that associated with conventional orthopedic surgeries, such as osteosynthesis, spine surgery, or arthroplasty. Surgical site infections remain a critical and frequent complication of surgical treatment of soft-tissue malignancies and often result in prolongation of hospital stay. Although practical options to prevent surgical site infections seem quite limited, the present data provide a rationale for perioperative evaluation in patients at a high risk of surgical site infections.
    No preview · Article · Nov 2011 · Journal of Orthopaedic Science
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    ABSTRACT: Plasma d-dimer levels have been associated with the status of tumor progression or oncological outcomes in cancer. Although there are many evidences suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no clinical data on d-dimer levels and oncological outcome of musculoskeletal sarcoma has been reported. In this study, we included a total of 85 patients who were diagnosed with musculoskeletal sarcoma and treated at our institute. Plasma d-dimer levels were determined before performing any clinical intervention, including open biopsy, chemotherapy, radiotherapy or tumor resection. We evaluated the effect of d-dimer levels and other clinicopathological factors on oncological outcomes of patients. Upregulation of plasma d-dimer levels proved to be an independent risk factor for metastasis and lethal outcome of patients with musculoskeletal sarcoma. Upregulation of plasma d-dimer levels were indicated poor oncological outcome in metastasis and total survival rate of musculoskeletal sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the tumor progression status and prognosis of musculoskeletal sarcoma.
    Preview · Article · Nov 2011 · BMC Musculoskeletal Disorders
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    Preview · Article · Jul 2011 · Journal of Orthopaedic Science
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    ABSTRACT: We have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects. DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1β or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed. Development of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1β and bFGF. Given the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA.
    No preview · Article · May 2011 · Journal of Orthopaedic Science
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    ABSTRACT: Desmoplastic fibroblastoma (collagenous fibroma) is a recently described tumor thought to arise predominantly from subcutaneous tissue or skeletal muscle. The natural evolution of this tumor on magnetic resonance imaging has never been described, to the best of our knowledge. We herein report a case of desmoplastic fibroblastoma arising in the thigh and show the longitudinal magnetic resonance imaging findings. A 60-year-old Japanese man presented with swelling of the medial side of his right thigh, and he complained of nighttime pain and slight tenderness. Magnetic resonance imaging demonstrated a 4 × 4 cm mass in the right thigh. Open biopsy was performed. The mass was diagnosed histologically as a benign fibrous tumor, and we maintained follow-up without surgical therapy. After one year, magnetic resonance imaging showed an increase in tumor size to 4 × 5 cm, but the histologic findings were the same as those obtained one year earlier. Resection was performed with narrow surgical margins. Pathologic diagnosis was desmoplastic fibroblastoma. Two years after surgery, the patient is free from pain and shows no signs or symptoms of recurrence. The natural evolution of desmoplastic fibroblastoma is characterized by no changes in patterns on magnetic resonance imaging despite increasing size. This finding is clinically helpful for distinguishing desmoplastic fibroblastoma with increasing pain from the desmoid tumor.
    Preview · Article · Apr 2011 · Journal of Medical Case Reports

  • No preview · Article · Mar 2011 · Journal of Orthopaedic Science
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    ABSTRACT: Malignant pigmented villonodular synovitis (PVNS) (or malignant giant cell tumor of tendon sheath (GCTTS) is an extremely rare condition defined as a malignant lesion occurring with concomitant or previously documented PVNS at the same site. To date, only less than 20 cases have been reported in English literatures. We report a case of malignant PVNS in the knee in a 56-year-old woman with unpredictable rapid progression. This case raised a caution that when atypical components in specimens of recurrent benign PVNS are detected, even if low-grade or tiny, both pathologists and surgeons should consider the risk of malignant PVNS, which could display aggressive clinical progression.
    Full-text · Article · Jan 2011 · The Open Orthopaedics Journal
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    ABSTRACT: Although patients with musculoskeletal tumors are at risk of venous thromboembolism (VTE), few detailed studies on the incidence, clinical course, and risk factors of this condition have been reported. A total of 299 patients with musculoskeletal tumors during the preceding 3 years were enrolled. D-dimer (DD) levels on admission and on postoperative days 1, 7, and 14 were routinely assessed. For patients who were receiving chemotherapy, an examination was performed every 2-3 days for the survey. Multidetector-row computed tomography (MDCT) was used for the detection of VTE in patients with DD levels > 10 μg/ml. The incidence of clinically detected VTE and the clinical courses of the patients with VTE were reviewed. The risk factors for VTE were analyzed. For statistical analysis, Fisher's exact test, the Mann-Whitney U-test, and logistic regression were used. VTE was detected in eight cases (2.7%). Six cases were detected postoperatively, and the remaining two cases were detected during chemotherapy. Pulmonary embolism was evident in four cases. No VTE-related lethal events were detected during the study period. In the univariate analysis, malignancy (P = 0.003), chemotherapy (P = 0.004), plastic surgery (P = 0.006), tumor size (P = 0.008), and elevated DD levels at admission (P = 0.03) were found to be significant risk factors for VTE. Among these factors, the multivariate analysis indicated that tumor size (P = 0.00 006), plastic surgery (P 0. 01), and chemotherapy (P = 0.02) were independent risk factors. The incidence and risk factors for VTE in the management of musculoskeletal tumor patients by screening DD levels combined with MDCT were analyzed. For patients at risk, prospective surveys for VTE should be considered in the future.
    No preview · Article · Nov 2010 · Journal of Orthopaedic Science
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    ABSTRACT: Understanding the mechanisms of drug resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is essential to develop novel chemotherapies for non-small cell lung cancer (NSCLC). Therefore, we analyzed the expression and function of ATP-binding cassette (ABC) transporters in EGFR TKI-resistant NSCLC. In three newly established AG1478-resistant NSCLC cell lines, we evaluated the expression profile of ABC transporters and genotyping of ABCG2 by real-time polymerase chain reaction and elucidated their function by Hoechst dye efflux analyses. The growth-inhibitory effect of the topoisomerase I inhibitor Hoechst 33342, which is extruded by ABCG2, was also investigated in these cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. In AG1478-resistant cells, significantly less ABCG2 was expressed, and the ratios of the cells with a strong ability to extrude Hoechst dye were remarkably smaller than in the parent cells. Because of the ABCG2 downregulation and loss of function due to C421A/C421A homozygosity, PC-14AG50R was thus considered to be more sensitive to Hoechst 33342 than the parental cells. All AG1478-resistant cells were more sensitive to the combination of Hoechst 33342 and AG1478 than to single agent. Resistance to EGFR TKI in NSCLC is associated with the downregulation of ABCG2 expression. A topoisomerase I inhibitor alone or in combination with EGFR TKI might offer a promising strategy for treating NSCLC that is resistant to EGFR TKI.
    No preview · Article · Nov 2010 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

Publication Stats

285 Citations
74.99 Total Impact Points


  • 2008-2015
    • Kyorin University
      • Department of Orthopaedic Surgery
      Edo, Tokyo, Japan
  • 2000-2009
    • Keio University
      • Department of Orthopedic Surgery
      Edo, Tōkyō, Japan
  • 2003
    • Harvard Medical School
      Boston, Massachusetts, United States