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Publications (16)47.71 Total impact

  • Article: Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas: more than a 24-month median follow-up.
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    ABSTRACT: BACKGROUND: Renal cell carcinoma (RCC) is thought to respond unreliably to radiotherapy (RT). Zoledronic acid significantly reduces the risk of skeletal complications. This study investigated whether RT with zoledronic acid prolonged the time to bone-lesion progression in comparison with RT alone. METHOD: Twenty-seven patients (34 lesions) with bone metastases secondary to RCC undergoing treatment with RT with or without zoledronic acid were retrospectively evaluated at two institutions between 1999 and 2009. Twelve patients were treated with RT alone from 1999 to 2008 (RT group). Fifteen patients were treated with RT and zoledronic acid from 2006 to 2009 (RT + Z group). The time to skeletal-related events and pain progression were assessed from patients' medical records. RESULTS: The median (range) follow-up was 26 (3-75) and 24 (3-55) months in the RT and RT + Z groups, respectively. Three patients (three lesions) in the RT + Z group had skeletal-related events (SREs). In contrast, six patients (eight lesions) in the RT group had SREs. SREs comprised pathological fractures in five, additional surgeries in three, spinal cord or cauda equine compression in two, and repeat RT in one. There was a significant difference in SRE-free survival time and duration of site-specific pain response between groups. CONCLUSIONS: RT combined with zoledronic acid significantly prolonged SRE-free survival and duration of pain response compared with RT alone in the treatment of osseous metastases from RCC.
    Journal of Orthopaedic Science 10/2012; · 0.84 Impact Factor
  • Article: Clinical outcomes of the KYOCERA Physio Hinge Total Knee System Type III after the resection of a bone and soft tissue tumor of the distal part of the femur.
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    ABSTRACT: The KYOCERA Physio Hinge Total Knee System Type III (PHKIII) was developed to reconstruct bony defects of the distal femur. The PHKIII is originative in that the metallic parts are fully made of titanium alloy, and this prosthesis has a unique semi-rotating hinge joint and was designed especially for people with the Asian physical body-type. The clinical outcomes of the PHKIII after the resection of musculoskeletal tumors of the distal femur were evaluated. There were 41 males and 28 females with a median age of 48-years. The median duration of follow-up was 57 months. Eleven early complications and 37 late complications were observed, including 10 recurrences, 7 deep infections, 7 aseptic loosenings, 4 stem breakages, 4 displacements of shaft cap, and one wear of rotation sleeve. Twenty four prosthesis (35%) required a secondary operation because of complications. The five-year overall prosthetic survival rates, -prosthetic survival rate without aseptic loosening, and -limbs preservation rate were 85%, 90%, and 86%, respectively. The mean functional score according to the classification system of the Musculoskeletal Tumor Society was 20.5 points (68%). Although continuous follow-up is required, reconstructions using PHKIII are considered to achieve more acceptable functional results.
    Journal of Surgical Oncology 03/2011; 103(3):257-63. · 2.10 Impact Factor
  • Article: Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J.
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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. · 0.84 Impact Factor
  • Article: Osteosarcoma in the elderly over 60 years: a multicenter study by the Japanese Musculoskeletal Oncology Group.
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    ABSTRACT: Few studies have described the characteristics and prognostic factors of osteosarcoma patients aged over 60 years. The Japanese Musculoskeletal Oncology Group (JMOG) carried out a retrospective review of patients over the age of 60 years with osteosarcoma. Only 12 patients had secondary osteosarcoma, with none associated with Paget's disease. The primary disease sites were the extremities in 63% and trunk in 33%. The overall survival was 42.8% and disease-free survival was 40.8% at 5 years in the high grade group. An univariate analysis indicated that significant poor prognostic factors for overall survival were axial location, lung metastasis at initial presentation, and absence of surgical treatment. Multivariate analysis revealed that a significant poor prognostic factor for overall survival was the absence of surgical treatment. Secondary osteosarcoma did not lower the overall or the disease-free survival in any group. The current study indicates that the number of osteosarcoma patients over 60 years is increasing. The number of cases with secondary osteosarcoma over 60 years is relatively small in Japan, with no patients having osteosarcomas related to Paget's disease. Although there is a predilection for axial localization, surgical treatment has a significant impact on patient's prognosis.
    Journal of Surgical Oncology 05/2009; 100(1):48-54. · 2.10 Impact Factor
  • Article: CLEAR CELL CHONDROSARCOMA: A Report of Two Cases and Review of Literature
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    ABSTRACT: Two cases of clear cell chondrosarcoma located in the distal femur and proximal humerus are reported. Both patients were men aged 35 and 51 years. Their initial symptom was a pathologic fracture. Roentgenographically, one patient showed a purely lytic lesion and another lytic with centrally radiodensity. Microscopic examination revealed that the tumor cells have a centrally placed vesicular nucleus surrounded by a clear cytoplasm, with distinct boundaries. Their cytoplasm stained with S-100 protein by the peroxidaseantiperoxidase method. We found 36 reported cases (including the two reported here), and delineated the clinico-pathologic characteristics of the disease. ACTA PATHOL. JPN. 36: 1577-1585, 1986.
    Pathology International 12/2008; 36(10):1577 - 1585. · 1.62 Impact Factor
  • Article: Current state of extendable prostheses for the lower limb in Japan.
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    ABSTRACT: With the cooperation of the Japanese Musculoskeletal Oncology Group (JMOG), we conducted a questionnaire survey to assess the status of extendable prosthesis use after resection of malignant bone tumors in children. The subjects were 28 patients (mean age, 10.1 years). Osteosarcoma was the most frequent tumor, and all patients had undergone preoperative chemotherapy and wide resection. The prosthesis was the Growing Kotz-type in 26 patients. The mean predicted leg length discrepancy was 67.7mm, mean stem diameter 10mm, mean number of elongations 2.1, and mean total elongation 35.4mm. Infection was observed in one patient with a mean functional assessment of 75%. In Japan, extendable prostheses, as represented by the Growing Kotz-type, provide a useful limb reconstruction method, with a minimum of major complications and with good function of the affected limb. However, a long-term follow-up survey is necessary.
    Surgical Oncology 09/2008; 17(2):65-71. · 2.44 Impact Factor
  • Article: Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.
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    ABSTRACT: Since the prognosis of human osteosarcoma in advanced stage remains poor, the development of new and effective therapies including immunotherapy is required. To identify tumor-associated antigens of osteosarcoma applicable to the immunotherapy of this malignancy, we employed the serological analysis of recombinant cDNA expression library (SEREX) technique that defines tumor antigens recognized by the humoral immune system. Screening a cDNA library derived from an osteosarcoma cell line MG63 with sera from osteosarcoma patients identified 43 positive clones, representing 14 distinct antigens. Among them, CLUAP1 (clusterin-associated protein 1) was highly expressed in osteosarcoma tissue samples and cell lines. Overexpression of CLUAP1 was observed in other malignancies including ovarian, colon, and lung cancers. Our results suggest that CLUAP1 may be useful as a prognostic/diagnostic marker and/or for a target of immunotherapy of osteosarcoma.
    International Journal of Oncology 03/2007; 30(2):461-7. · 2.40 Impact Factor
  • Article: Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.
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    ABSTRACT: Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.
    Journal of Orthopaedic Science 06/2005; 10(3):258-63. · 0.84 Impact Factor
  • Article: Extraskeletal myxoid chondrosarcoma: a Multi-Institutional Study of 42 Cases in Japan.
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    ABSTRACT: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment. Forty-two cases of EMC, which had been identified from files of eight affiliated hospitals and confirmed for histologic diagnosis at the Pathology Center, were analyzed for histologic grade, demographics, treatments, outcomes, and prognostic factors. The average follow-up period was 7.4 years. Included in the study were 20 men and 22 women with a mean age at diagnosis of 52.1 years. The tumors were located mainly in the lower extremities (69%). Thirty-three tumors (79%) were classified as Grade 1 and nine as Grade 2 according to the modified French System. Overall survival was 100% at 5 years and 88% at 10 years. Disease-free survival was 45% at 5 years and 36% at 10 years. Inadequate initial surgery was defined as a significant risk factor for local recurrence by univariate analysis of all 42 patients but not by the analysis of those 30 patients who had undergone wide tumor excision or amputation. Wide excision led to the recurrence rate of 14%. These findings supported the role of wide excision in the local control of EMC, irrespective of the previous excision procedure or recurrence. The protracted clinical course of the tumors and the presence of patients who had distant metastasis develop after definitive surgery of the primary tumor represented EMC as intermediate malignancy.
    Cancer 04/2003; 97(5):1285-92. · 4.77 Impact Factor
  • Article: Recognition by cellular and humoral autologous immunity in a human osteosarcoma cell line.
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    ABSTRACT: Because of the difficulty of developing pairs of osteosarcoma cell lines and cytotoxic T lymphocytes (CTLs), no osteosarcoma tumor antigens that are useful for antiosteosarcoma immunotherapy have yet been identified. In parallel with continuous attempts to develop such pairs from osteosarcoma, we employed serological identification using a recombinant expression cloning (SEREX) method to identify B cell-defined antigens. Consequently, a human osteosarcoma cell line, OS2000, was established from a primary osteosarcoma of a patient cured of hereditary retinoblastoma. Repetitious in vitro stimulations by OS2000 cells to the autologous peripheral T cells induced cytotoxic activity in the autologous osteosarcoma cells but not in the nontumor cells. The cytotoxicity was inhibited by anti-HLA class I monoclonal antibody. SEREX analysis revealed that autologous humoral immunity reacted to two proteins expressed in OS2000. One was the self HLA-Cw*0102 molecule, and the other was wild-type smooth muscle myosin light chain (SMMLC). However, no antigenicity of these proteins was seen versus the sera of the other patients. In conclusion, our results demonstrated the presence of host cellular and humoral immune responses to autologous osteosarcoma cells. This offered the opportunity to identify osteosarcoma antigens recognized by autologous immunity.
    Journal of Orthopaedic Science 02/2003; 8(4):554-9. · 0.84 Impact Factor
  • Article: Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese Musculoskeletal Oncology Group study.
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    ABSTRACT: The prognostic value of the time of identification of lung metastasis was investigated in 280 patients with metastatic lung osteosarcoma as a multi-institutional study of the Japanese Musculoskeletal Oncology Group. The 280 patients with lung metastasis were divided into four groups: group 1, patients with lung metastasis identified at initial presentation; group 2, those with lung metastasis identified during preoperative chemotherapy; group 3, those with lung metastasis identified during postoperative chemotherapy, and group 4, those with lung metastasis identified after completion of treatment. Survivals of the four groups were compared. Additionally, the effects of number of metastatic nodules, metastasectomy, and the effect of chemotherapy on the primary tumor on survival of the four groups were analyzed. There were 46 patients in group 1, 30 in group 2, 94 in group 3, and 110 in group 4. The overall 2-year survival rates from the time of identification of lung metastasis were 33%, 31%, 24%, and 40% for groups 1, 2, 3, and 4, respectively, whereas the 5-year survival rates were 18%, 0%, 6%, and 31%, respectively. Patients in group 4 thus demonstrated significantly better prognosis than any of the other patients (P <.0001). Time of identification of lung metastasis is an important prognostic factor. In terms of clinical behavior, groups 2 and 3 are completely different than group 4. These data ensure the need to stratify stage III osteosarcomas into subgroups according to the time of diagnosis of lung metastases. To improve the survival of osteosarcoma patients, new treatment modalities should be introduced into the treatment armamentarium for lung metastasis from osteosarcoma, especially in groups 1, 2, and 3.
    Journal of Clinical Oncology 08/2002; 20(16):3470-7. · 18.37 Impact Factor
  • Article: ErbB2 expression is correlated with increased survival of patients with osteosarcoma.
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    ABSTRACT: Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high-grade osteosarcoma. ErbB2 status was determined immunohistochemically in biopsy specimens of osteosarcoma of the extremities from 81 patients who were treated with surgery and chemotherapy. None of the patients had metastatic disease at presentation (Stage II), and all were followed-up for at least five years. The ErbB2 status was analyzed in relation to the lengths of event-free and overall survival. Of the 81 tumors examined, 51 (61%) demonstrated high levels of ErbB2 expression. The presence of increased levels of ErbB2 in osteosarcoma was significantly associated with the increased probability of event-free (72.2% v. 45.6% at 5 years, P = 0.03) and overall survival (79.7% v. 58.2% at 5 years, P = 0.03). Cox multivariate analysis showed that the risk of adverse events and death was increased substantially (rate ratio: 2.24 and 2.54; 95% confidence interval, 1.07-4.72 and 1.09-5.67, respectively) among patients with decreased levels of ErbB2 protein in tumor cells, as compared with patients who had increased levels of ErbB2 in tumor cells. In patients with high-grade osteosarcoma without metastatic disease at presentation and treated with surgery and chemotherapy, the presence of increased levels of ErbB2 in tumor cells is associated with a significantly increased probability of event-free and overall survival. Further data are needed before this marker can be used in making clinical decisions.
    Cancer 04/2002; 94(5):1397-404. · 4.77 Impact Factor
  • Article: Complications associated with bone cementing for the treatment of giant cell tumors of bone.
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    ABSTRACT: Aretrospective review was conducted of giant cell tumors treated between 1984 and 1998 using the technique of aggressive curettage through a large bone window followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up time of 46 months (range, 24-188 months) were identified. One patient had a local recurrence 24 months postoperatively. All the patients showed a radiolucent zone at the bone-cement interface up to 2.5 mm in width during the first 6 months after operation. However, the radiolucent zones were nonprogressive and did not affect the stability of the bone cement. Osteoarthritis of the knee joint occurred 14 years postoperatively in one patient with an intraarticular fracture at presentation. A stress fracture occurred in one patient who had the largest tumor in the distal femur. Acrylic cement reconstruction is a safe and effective procedure that provides local adjuvant therapy. Giant cell tumors with an associated intraarticular fracture remain a challenging problem to treat.
    Journal of Orthopaedic Science 02/2002; 7(2):194-8. · 0.84 Impact Factor
  • Article: Hyperplastic callus formation in both femurs in osteogenesis imperfecta
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    ABSTRACT:  A 3-year-old boy with osteogenesis imperfecta had hyperplastic callus formation in the right femur, without preceding trauma or fracture. Radiologically, this bony mass in the femoral shaft mimicked osteosarcoma. Open biopsy showed that it was benign and suggested hyperplastic callus formation. Seven months after the biopsy, the hyperplastic callus had practically vanished. A similar process developed in the left femur 1 year later, also without fracture.
    Skeletal Radiology 04/1996; 25(4):384-387. · 1.54 Impact Factor
  • Article: Limb-saving surgery in osteosarcoma by vascularized fibular graft
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    ABSTRACT: Osteosarcoma is the most malignant bone tumor of the extremities that occurs in younger age groups; however, the prognosis of this disease has been improving. Limb-saving procedures have been successfully performed in more than half of the new cases of this disease. Because osteosarcoma occurs in young patients and their life expectancy is generally long, the rescued limbs must provide as full a service as possible for several decades. We have attempted the rescue of limbs in osteosarcoma patients, using the vascularized fibular graft (VFG). We performed a retrospective clinical and radiographic review of 12 patients with at least 3 years of follow up. The results were satisfactory in 11 out of the 12 patients from both the oncologic and functional point of view. There were no severe complications or donor site morbidity. Functional status, evaluated according to the system of Enneking et al. (Enneking WF, Dunham W, Gebhart MC, et al. A system for functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clin Orthop 1993;286:241–246), with some modifications exceeded 80%, except in one patient. The results of this study suggest that, because of the resulting durability of the reconstructed limb, VFG should be considered for limb rescue in young patients with osteosarcoma.
    Journal of Orthopaedic Science 12/1995; 1(1):4-10. · 0.84 Impact Factor
  • Article: Characteristics of Human Soft Tissue Sarcomas in Xenografts and In Vitro
    Clinical Orthopaedics and Related Research 02/1983; 173:251-261. · 2.53 Impact Factor