Faculty Profiles - KUNISADA Toshiyuki

Papers - KUNISADA Toshiyuki

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Effect of dose intensity of methotrexate, doxorubicin, and ifosfamide on the prognosis of patients with osteosarcoma Reviewed

Yoichiro Uchida, Toshifumi Ozaki, Akira Kawai, Toshiyuki Kunisada, Tomoyuki Dan'ura, Noriko Naito, Hajime Inoue

International Journal of Clinical Oncology 4 ( 1 ) 36 - 40 1999.2

Language：English Publishing type：Research paper (scientific journal)

Background. The prognosis of patients with osteosarcoma has improved due to the introduction of systemic chemotherapy. The current study tried to identify the effect of each anti-tumor drug on the prognosis of patients with osteosarcoma. Methods. The records of 29 patients with osteosarcoma who received systemic chemotherapy were retrospectively analyzed. All tumors were classified as stage IIB (Enneking's surgical stage) and were located around the knee joint or more distal areas. The histologic response to preoperative chemotherapy was determined in 20 patients: 9 patients had grade 1, 4 grade 2, 5 grade 3, and 2 grade 4. The mean follow-up period was 102 months. Results. The 5-year overall survival and relapse-free survival (RFS) in the 29 patients was 47.7% and 41.4%, respectively. The 5-year RFS for the 7 good responders (grade 3 and 4) was 85.7%, and that for the 13 poor responders (grade 1 and 2) was 23.1% (P = 0.008). The mean preoperative dose intensity (DI) of methotrexate (MTX) for good responders was significantly higher than that for poor responders (P = 0.028). In 23 patients who received MTX and doxorubicin (ADR) but not ifosfamide (IFOS), the DI of MTX significantly influenced the RFS (P = 0.0128). In the 13 poor responders, 6 of whom received IFOS, the DI of IFOS and ADR significantly influenced RFS (P = 0.0112, 0.0395). Conclusion. The preoperative DI of MTX was related to the histologic response rate. The DI of MTX was significantly associated with the patients' RFS. In poor responders, the DI of IFOS and ADR influenced the patients' RFS.

DOI： 10.1007/s101470050021

High complication rate of reconstruction using Ilizarov bone transport method in patients with bone sarcomas Reviewed

T Ozaki, Y Nakatsuka, T Kunisada, A Kawai, T Dan'ura, N Naito, H Inoue

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 118 ( 3 ) 136 - 139 1998.12

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER VERLAG

We performed five reconstructions by bone transport in patients with bone sarcoma: three osteosarcomas, one Ewing's sarcoma and one chondrosarcoma. Four sacromas were in the distal femur and one in the shaft of the tibia. Four patients received multidrug chemotherapy. The average length of the skeletal defect after tumour resection was 17 (range 10-25) cm. All patients underwent double elongation from both proximal and distal sites: of the bone defect. The average follow-up period was 48 (range 40-66) months, and the average duration of external fixation was 32 months (range 579-1340 days). In one case, bone formation was satisfactory, but in the other cases, it was poor and slow. The average treatment index was 95 (range 53-191) days per 1 cm of elongation. In one case, the bone fragment disappeared during the bone transport. In one case, the end of the bone protruded from the skin, and osteomyelitis set in. This patient underwent above-knee amputation due to failure of infection control. Three patients suffered talipes equinus. One patient died of pulmonary metastasis. Two patients had fair and three had poor function. This method is not recommended for patients with bone sarcoma who may have a poor prognosis, as it has an unacceptably high complication rate.

A new human chondrosarcoma cell line (OUMS-27) that maintains chondrocytic differentiation Reviewed

T Kunisada, M Miyazaki, K Mihara, C Gao, A Kawai, H Inoue, M Namba

INTERNATIONAL JOURNAL OF CANCER 77 ( 6 ) 854 - 859 1998.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

A new human chondrosarcoma cell line, OUMS-27, was established. Monolayer cultures consisted of elongated polygonal cells with a doubling time of 41 hr and a plating efficiency of 2.1%. After reaching confluence, the cells continued to slowly proliferate and formed nodule-like structures, which showed metachromasia when stained with toluidine blue, indicating the presence of proteoglycan. The cells in the nodules were round to polygonal in shape, multilayered and surrounded by abundant extracellular matrix. Types I, II and III collagens were identified by Northern blotting and immunostaining. The cells formed colonies (0.1%) in 0.3% soft-agar medium 3 weeks after inoculation. Inoculation of cells into athymic mice resulted in the formation of tumors at the injection site, resembling the original chondrosarcoma. These results demonstrated that OUMS-27 cells expressed a differentiated chondrocytic phenotype. Moreover, OUMS-27 cells had p53-gene mutation. Thus, the OUMS-27 cell line can provide a useful model not only for studies on human chondrocyte but also for basic studies on the diagnosis, treatment and etiology of human chondrosarcoma. (C) 1998 Wiley-Liss, Inc.

Treatment outcome of osteofibrous dysplasia Reviewed

T Ozaki, M Hamada, S Sugihara, T Kunisada, S Mitani, H Inoue

JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B 7 ( 3 ) 199 - 202 1998.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

The disease course of six tibial lesions in five patients with osteofibrous dysplasia who were followed longer than 10 years (average: 16.8 years) was analyzed retrospectively. Three patients had a lesion of the unilateral tibia; one patient had lesions of the unilateral tibia and fibula; and one patient had lesions of the bilateral tibiae and ulnae. Curettage and autogeneic bone graft were performed on two lesions, which then healed. Of four lesions on which curettage and xenogeneic bone grafts were performed, three lesions healed, and one developed local recurrence. Curettage and xenogeneic bone graft were performed on the recurrent lesion, which finally healed and the deformity stopped. Three lesions healed without surgical treatment. During the long-term follow-up, this disease showed a clear tendency of healing. Surgical treat ment should be considered in patients with disease uncontrollable by conservative treatment or those who have a high possibility of impending fracture and progressing deformity.

Reconstruction of bone defect using the bone transport technique for a case of osteosarcoma of the femur Reviewed

T Ozaki, Y Nakatsuka, A Kawai, H Akazawa, T Kunisada, H Inoue

ACTA MEDICA OKAYAMA 52 ( 1 ) 67 - 70 1998.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

There are few reports on skeletal reconstruction using the bone transport technique to repair bone defects caused by resections of tumors associated with osteosarcoma. We attempted to reconstruct a 23 cm bone defect after resection of an osteosarcoma of the left femur, and succeeded in gaining 17 cm by bone transport. Five years after surgery, this patient remains alive without metastasis or local recurrence.

Value of thallium-201 scintigraphy in bone and soft tissue tumors Reviewed

Osamu Sato, Akira Kawai, Toshifumi Ozaki, Toshiyuki Kunisada, Tomoyuki Danura, Hajime Inoue

Journal of Orthopaedic Science 3 ( 6 ) 297 - 303 1998

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Japan

The potential role of thallium-201 (201Tl) scintigraphy in the imaging of various musculoskeletal tumors was investigated in 80 patients. Uptake of 201Tl was observed in 17 (100%) malignant bone tumors, 6 (100%) giant cell tumors, and 2 of 8 (25%) benign bone tumors. Nineteen of 30 malignant soft tissue tumors (63%) were positive for 201Tl scintigraphy, while 2 of 14 benign soft tissue tumors (14%) yielded positive results. None of 6 liposarcomas were visualized by 201Tl scintigraphy. There was no 201Tl uptake in the tissues of 5 non-tumorous conditions. Ten patients with osteosarcoma were evaluated by 201Tl scintigraphy both pre- and post- chemotherapy. There was a significant correlation between changes in tumor- to-normal count ratio and percent necrosis of the resected tumor. The mean decrease in tumor-to-normal count ratio was 71% for patients with ≥90% tumor necrosis and 26% for those with &lt
90% tumor necrosis. Serial 201Tl scintigraphy, with quantitative analysis of alterations in 201Tl uptake, may provide a quantitative and objective measure of the effect of preoperative chemotherapy in patients with malignant bone tumors.

DOI： 10.1007/s007760050056

Vancomycin-impregnated polymethylmethacrylate beads for methicillin- resistant Staphylococcus aureus (MRSA) infection: Report of two cases Reviewed

Toshifumi Ozaki, Teruhito Yoshitaka, Toshiyuki Kunisada, Tomoyuki Dan'ura, Noriko Naito, Hajime Inoue

Journal of Orthopaedic Science 3 ( 3 ) 163 - 168 1998

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Tokyo

Two patients with methicillin-resistant Staphylococcus aureus (MRSA) infection were treated with vancomycin (VCM)-impregnated polymethylmethacrylate (PMMA) beads. One patient, who had a history of polycystic kidney and diabetes mellitus, who was receiving hemodialysis due because of non-functional kidney, underwent resection of an intermediate grade chondrosarcoma in the pelvis. MRSA infection developed and curettage of the lesion was performed, but MRSA infection recurred. During the second revision surgery, VCM-impregnated PMMA beads were implanted. MRSA infection has not recurred for 16 months since the implantation of the VCM beads. The second patient had a history of total hip arthroplasty (THA) performed because of coxarthrosis. After the initial surgery, MRSA infection developed, recurring after the second revision surgery for THA. After curettage following removal of the prosthesis, VCM beads were implanted with a spacer composed of VCM-PMMA and a Luque rod. Infection did not recur and THA revision was performed 3 months after the VCM beads implantation. Fifteen months after the last revision surgery, infection has not recurred.

DOI： 10.1007/s007760050037

Surgical Treatment of Metastatic Bone Tumor Affecting Lower Extremity.

KUNISADA Toshiyuki, OZAKI Toshifumi, DOI Takeshi, DAN'URA Tomoyuki, INOUE Hajime

The Journal of the Chugoku-Shikoku Orthopaedic Association 10 ( 2 ) 285 - 288 1998

Language：Japanese Publisher：The Chugoku-Shikoku Orthopaedic Association

We evaluated the results of surgical treatment of 15 metastatic lesions affecting long bones in 14 patients. Pathological fractures occured in 7 patients preoperatively. Pain due to bone metastasis subsided after the operation in 12 of 14 lesions with pain preoperatively. Since after surgery pain subsided in patients who had not suffered a pathological fracture preoperatively, we considered that prophylactic surgical treatment would be effective to control pain due to bone metastasis in a long bone. In this series, the results of surgical treatment were excellent in 4 patients, good in 6, and fair in 2. Intramedullary fixation would be a useful treatment on bone metastasis affecting long bones. Wide resection should be attempted in patients who may have a good prognosis.

DOI： 10.11360/jcsoa1989.10.285

Effects of simulated microgravity on human osteoblast-like cells in culture Reviewed

T Kunisada, A Kawai, H Inoue, M Namba

ACTA MEDICA OKAYAMA 51 ( 3 ) 135 - 140 1997.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Physiological strain plays an important role in maintaining the normal function and metabolism of bone cells. It is well known that the mineral content of astronauts' bones decreases during spaceflight, Thus, gravity is one of the important factors in the muscloskeletal system. The vector-free horizontal clinostat has been used to simulate conditions of microgravity for examining such effects on cells in culture. We analyzed the effects of simulated microgravity using a horizontal clinostat on cultured osteoblast-like cells (HuO9 cell line). Total cellular protein, which was measured as an indication of cell proliferation, was not significantly inhibited under simulated microgravity conditions. No morphological changes were detected under microgravity conditions by phase-contrast microscopy. However, the alkaline phosphatase (ALP) activity and osteocalcin production of the HuO9 cells decreased significantly under microgravity conditions. Our data indicate that simulated microgravity directly inhibits some differentiation phenotypes and some functions of osteoblasts. On the other hand, the addition of 1,25-dihydroxy-vitamin D-8 (1,25-(OH)(2)-D-3) increased ALP activity under simulated microgravity conditions, although the total activity of ALP in the cells treated with 1,25-(OH)(2)-D-3 was still lower under simulated microgravity conditions than that in the control cells. However, the cells under simulated microgravity conditions showed a greater enhancement of ALP activity by treatment with 1,25-(OH)(2)-D-3.

Imaging assessment of the response of bone tumors to preoperative chemotherapy Reviewed

A Kawai, S Sugihara, T Kunisada, Y Uchida, H Inoue

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH ( 337 ) 216 - 225 1997.4

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT-RAVEN PUBL

Assessment of the response of bone tumors to preoperative chemotherapy is of clinical importance. The authors determined the value of 3 imaging techniques (digital subtraction angiography, thallium scintigraphy, and dynamic magnetic resonance imaging) in guiding patient management by assessing the response of 17 bone sarcomas to preoperative chemotherapy compared with histologic evaluation of the resected specimens. Digital subtraction angiography showed a sensitivity of 87.5 %, specificity of 57.1%, and accuracy of 73.3%. Thallium scintigraphy (sensitivity, 85.7%; specificity, 85.7%; accuracy, 85.7%) was superior to angiography in predicting tumor responses. The results of dynamic magnetic resonance imaging were analyzed on the basis of the value of slopes, which represents the percent increase in signal intensity per minute. The differences in slope before and after chemotherapy and the postchemotherapy slope values correlated with the histologic responses. The assessment by dynamic magnetic resonance imaging showed a sensitivity of 100%, specificity of 85.7%, and accuracy of 90.9%. Thallium scintigraphy and dynamic magnetic resonance imaging were considered noninvasive, reliable techniques that had about equal ability to assess the response of bone sarcomas to preoperative chemotherapy. Dynamic magnetic resonance imaging offers major advantages in the spatial resolution and can be more readily quantitated when compared with thallium scintigraphy.

A clinical analysis of malignant schwannoma Reviewed

T Kunisada, A Kawai, T Ozaki, S Sugihara, K Taguchi, H Inoue

ACTA MEDICA OKAYAMA 51 ( 2 ) 87 - 92 1997.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

In this study, we reviewed the clinical features of 11 patients with malignant schwannoma who were treated in our institute. Five patients had coexistent von Recklinghausen's disease and one of them showed multifocal occurrence. Patients with the centrally located tumors had a poorer prognosis than those with the others. The overall 3-year survival rate was 36%; 40% in patients with von Recklinghausen's disease and 33% in the others. At the time of the last follow-up, 9 patients had died of the tumor, one continued to be tumor free, and one was alive with tumor. Postoperative local recurrence developed in 5 patients (45%); 4 out of 6 patients (67%) who underwent a marginal excision and one out of 3 (33%) who underwent primary amputation. There was no local recurrence in patients after a wide excision with at least 3 cm of normal tissue removed surrounding the tumor in all directions. Nine patients (82%) developed pulmonary metastasis. The effect of adjuvant chemotherapy was not clear in this study. The high risk of pulmonary metastasis in this disease indicates the necessity of more effective adjuvant chemotherapy.

The importance of doxorubicin and methotrexate dose intensity in the chemotherapy of osteosarcoma Reviewed

A Kawai, S Sugihara, T Kunisada, M Hamada, H Inoue

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 115 ( 2 ) 68 - 70 1996.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER VERLAG

The relationship between dose intensity of cytotoxic agents and therapeutic results was examined in a retrospective analysis of 32 patients with non-metastatic high-grade osteosarcoma of the extremities. The average dose intensities of individual agents were 9.8 mg/m(2)/week for doxorubicin, 1.2 g/m(2)/week for methotrexate, and 10.5 so mg/m(2)/week for cisplatinum. The dose intensities of doxorubicin and methotrexate were significantly correlated with the clinical results, while that of cisplatinum was not. These results indicate that maximal dose intensification of doxorubicin and methotrexate is an important determinant of treatment outcome for patients with osteosarcoma.

The value of needle biopsy in the diagnosis of musculoskeletal tumors Reviewed

Akira Kawai, Kohji Taguchi, Shinsuke Sugihara, Toshiyuki Kunisada, Hajime Inoue

International Journal of Clinical Oncology 1 ( 1 ) 35 - 38 1996

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Japan

Background: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of the needle biopsy in the diagnosis of musculoskeletal tumors has not been established. It is essential to evaluate the accuracy and limitations of the procedure in musculoskeletal tumors. Methods:The diagnoses from 66 needle biopsies (bone, 37
soft tissue, 29) performed on 64 consecutive patients using a Jamshidi needle (bone tumors) or a Tru-cut needle (soft tissue tumors) were compared with the final diagnoses made by open biopsy and/or a definitive operation. Results: Fifty-eight specimens (87.9%) were judged to be adequate for histological examination. It was technically difficult to obtain undamaged cores from very hard bony lesions or sclerotic cyst walls. A pathologist with experience in musculoskeletal tumors was able to differentiate malignant tumors from benign lesions in 98.3% of the cases (bone, 100%
soft tissue, 96.4%) and arrive at a specific diagnosis in 91.4% (bone, 100%
soft tissue, 82.1%) when adequate cores were obtained. It was troublesome to distinguish a well-differentiated liposarcoma from a benign lipoma, or inflammatory lesions from benign tumorous conditions. The overall accuracy for needle biopsy was 80.3% (bone, 81.1%
soft tissue, 79.3%). There was no morbidity related to the procedure. Conclusion: The results indicate that needle biopsy is a safe and accurate technique for diagnosing musculoskeletal tumors. © JSCO/CLJ 1996.

DOI： 10.1007/BF02347266

Evaluation of soft tissue sarcomas response to preoperative treatment: Assessment by angiography, thallium scintigraphy, and dynamic MRI

Akira Kawai, Shinsuke Sugihara, Toshiyuki Kunisada, Osamu Sato, Hajime Inoue

International Journal of Clinical Oncology 1 ( 2 ) 93 - 99 1996

Language：English Publisher：Springer Japan

Background: Assessment of the response of soft tissue sarcomas to preoperative treatment is of significant clinical importance. However, there are few reports concerning the accuracy of each imaging technique in assessing the response of soft tissue sarcomas to preoperative treatment. Methods: The responses of 15 soft tissue sarcomas to preoperative treatment by digital subtraction angiography, thallium scintigraphy, and dynamic magnetic resonance imaging (MRI) were compared with histologic evaluation of the resected specimens. Tumors with at least 90% histologic necrosis were considered to be effectively treated. Results: The accuracy of each assessment technique was 58.3% for digital subtraction angiography, 80% for thallium scintigraphy, and 77.8% for dynamic MRI. Both the differences in slope before and after treatment and the posttreatment slope values of dynamic MRI correlated with the histologic responses. Conclusion: Thallium scintigraphy and dynamic MRI showed sufficient value in the assessment of soft tissue sarcomas responses to preoperative treatment. Dynamic MRI had major advantages in its quantitative and spatial resolutions. © JSCO/CLJ 1996.

DOI： 10.1007/BF02348274

A Clinical Study of Eosinophilic Granuroma.

MASAOKA Shunji, KAWAI Akira, SUGIHARA Shinsuke, KUNISADA Toshiyuki, INOUE Hajime

The Journal of the Chugoku-Shikoku Orthopaedic Association 8 ( 2 ) 435 - 439 1996

Language：Japanese Publisher：The Chugoku-Shikoku Orthopaedic Association

We reviewed 13 cases of eosinophilic granuroma of the bone. There were 9 male and 4 female patients with an average age of 13.3 years (ranging from 2 to 33 years). Nine patients had solitary lesions and four had multiple lesions.<br>In all solitary cases and multiple cases with primary lesions, seven of the lesions were treated with curattage, six had curattage combined with bone graft and multiple cases with secondary lesions received no treatment. All lesions healed and local recurrence was not observed.<br>Eosinophilic granuroma of bone is a benign tumor. Therefore, it is important to perform a biopsy in order to determine the histology and not to treat it excessively.

DOI： 10.11360/jcsoa1989.8.435

Result of Hydroxyapatite Grafting for Treatment of Benign Bone Tumors.

KUNISADA Toshiyuki, KAWAI Akira, SUGIHARA Shinsuke, NISHIDA Keiichirou, HAMADA Masanori, INOUE Hajime

The Journal of the Chugoku-Shikoku Orthopaedic Association 7 ( 1 ) 7 - 12 1995

Language：Japanese Publisher：The Chugoku-Shikoku Orthopaedic Association

We applied hydroxyapatite (HAP) grafting clinically for 10 patients with defects produced by a curettage of benign bone tumors. The average follow up after surgery was 29 months (range 4 to 53 months). Physical and hematological findings during this period did not show any abnormalities. The radiographic evaluation of the incorporation of the implant was divided into four stages based on marginal findings and homogeneity of the grafted HAP. The margin of HAP became possibly unclear (stage II) an average of 3 months after surgery, and almost homogeneous with the surrounding bone (stage III) 11 months after surgery.

DOI： 10.11360/jcsoa1989.7.7

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