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Accurate diagnosis of musculoskeletal lesions by core needle biopsy. 国際誌

Goro Mitsuyoshi, Noriko Naito, Akira Kawai, Toshiyuki Kunisada, Aki Yoshida, Hiyoruki Yanai, Shuichi Dendo, Tadashi Yoshino, Susumu Kanazawa, Toshifumi Ozaki

Journal of surgical oncology 94 ( 1 ) 21 - 7 2006年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculoskeletal lesions. METHODS: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation. RESULTS: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure. CONCLUSION: The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.

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Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization. 査読国際誌

Nakagawa Y, Numoto K, Yoshida A, Kunisada T, Ohata H, Takeda K, Wai D, Poremba C, Ozaki T

Journal of cancer research and clinical oncology 132 ( 7 ) 444 - 450 2006年7月

Decreased levels of insulin-like growth factor-1 and vascular endothelial growth factor relevant to the ossification disturbance in femoral heads spontaneous hypertensive rats.

Takamitsu Komiyama, Keiichiro Nishida, Masanori Yorimitsu, Hideyuki Doi, Shinichi Miyazawa, Ai Kitamura, Aki Yoshida, Yoshihisa Nasu, Nobuhiro Abe, Toshifumi Ozaki

Acta medica Okayama 60 ( 3 ) 141 - 8 2006年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p<0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR.

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局所汗中乳酸測定の試み

片岡昌樹, 千田益生, 濱田全紀, 那須巧, 堅山佳美, 尾崎敏文

リハビリテーション医学 43 ( Suppl. ) S186 - S186 2006年5月

Magnetic resonance angiography without contrast enhancement medium in bone and soft tissue tumors. 国際誌

Hideyuki Doi, Atsushi Ono, Akira Kawai, Yuki Morimoto, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki

Oncology reports 15 ( 3 ) 681 - 5 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The aim of this study was to assess the ability of a new magnetic resonance (MR) angiography technique that does not use contrast enhancement medium to depict the vascularity of musculoskeletal neoplasms, and evaluate its clinical utility. We performed 3D fresh blood imaging (FBI) MR angiography in 57 patients with bone or soft tissue tumors, and the detection of vessels in and around the tumor was evaluated. Moreover, differences in vascularity between benign and malignant tumors were analyzed. In the lower leg, large arteries such as femoral or popliteal arteries were visible. In the trunk or arm, large vessels such as subclavian or iliac arteries were visible. Discrimination between benign and malignant tumors was impossible in bone tumors; however, the mean value of vascularity differed between benign and malignant tumors in the soft tissue tumors. This is the first trial of the FBI method for bone and soft tissue tumors. The still developing method of MRA without contrast materials could clearly depict major arteries in the trunk and the extremities, this method may replace conventional MRA of bone and soft tissue tumors because it produces vivid images while being non-invasive.

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Diagnosis of deep vein thrombosis after operation for fracture of the proximal femur: comparative study of ultrasonography and venography.

Motonobu Terao, Toshifumi Ozaki, Toru Sato

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 11 ( 2 ) 146 - 53 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: We compared investigative methods to study the diagnostic capability of ultrasonography. Subjects were 75 patients with proximal femur fractures who underwent surgery from March 2002 to December 2003. METHODS: Biochemical assays were carried out on days 3 and 7, and D-dimer levels were investigated as a time series. Ascending lower limb venography and ultrasonography were carried out nearly simultaneously in all cases on day 7. RESULTS: The incidence of deep vein thrombosis (DVT)-positive findings on venography was 61.3% (46/75). Venography results demonstrated a diagnostic sensitivity of 95.5% and specificity of 91.4% using a D-dimer cutoff of 1microg/ml on postoperative day 7. By ultrasonography, diagnostic sensitivity for DVT was 78.3%, and specificity was 96.5%. Among all proximal area cases, there were 18 limbs with DVT seen on venography among which were 17 limbs in cases demonstrating DVT at the same site on ultrasonography, a correct diagnosis rate of 94.4%. CONCLUSIONS: For the diagnosis of a thrombus more proximal than the popliteal area, a location at high risk for occurrence of pulmonary embolism, ultrasonography provided results nearly on par with those obtained by venography. Thus, we believe that ultrasonography allowed a more noninvasive, accurate diagnosis and more rapid treatment in cases where D-dimer values were 1 microg/ml or more on postoperative day 7.

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Lateral and posterior pillar grade changes during the treatment of Perthes disease in older patients using skin traction and range of motion exercises. 国際誌

Yoshihisa Sugimoto, Hirofumi Akazawa, Shigeru Mitani, Masato Tanaka, Tadashi Nakagomi, Koji Asaumi, Toshifumi Ozaki

Archives of orthopaedic and trauma surgery 126 ( 2 ) 101 - 4 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The lateral pillar (LP) grade changes detected during treatment periods have received a lot of attention recently. Lappin et al. reported LP collapses in 92 of 275 (33%) patients during the treatment, but did not provide information for comparing treatment methods and age of onset of the disease. The purpose of this study was to review radiological changes in LP grade in older patients with Perthes disease during 20 months of treatment with skin traction and ROM exercises. We have also reported any grade changes in the posterior pillar (PP) classification. MATERIAL AND METHODS: Twenty-one patients with unilateral disease who were 9 years or older at the onset of symptoms had been followed until skeletal maturity. RESULTS: Out of 21 older patients with Perthes disease, our study had two (9.5%) who experienced LP collapse and two (9.5%) who experienced PP collapse during the first 20 months of treatment. The average time from onset to hospitalization in hips, initially classified as LP group C and PP group C, was significantly longer than in LP and PP groups A and B. The LP collapse in two hips and PP collapse in two hips occurred during months 4-8 of treatment. On the other hand, of the patients allowed to ambulate with the Pogo stick orthosis from months 8 to 12 and without a brace from months 10 to 15, none had a collapse of their LPs or PPs during these periods. CONCLUSION: Lappin et al. reported that 92 of 275 patients (33%) who were managed conservatively in several hospitals experienced LP collapse during their treatment periods. Our results suggest that older patients with this disease treated with skin traction and ROM exercises rarely suffer a LP collapse, as compared with the Lappin et al. report.

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Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization. 国際誌

Yasuko Nakagawa, Aki Yoshida, Kunihiko Numoto, Toshiyuki Kunisada, Daniel Wai, Norihide Ohata, Ken Takeda, Akira Kawai, Toshifumi Ozaki

Oncology reports 15 ( 2 ) 297 - 303 2006年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying microarray CGH.

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Surgical results of sacral perineural (Tarlov) cysts.

Masato Tanaka, Shinnosuke Nakahara, Yasuo Ito, Kazuo Nakanishi, Yoshihisa Sugimoto, Hisanori Ikuma, Toshifumi Ozaki

Acta medica Okayama 60 ( 1 ) 65 - 70 2006年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

The purpose of this study was to investigate the surgical outcomes and to determine indicators of the necessity of surgical intervention. Twelve consecutive patients harboring symptomatic sacral perineural cysts were treated between 1995 and 2003. All patients were assessed for neurological deficits and pain by neurological examination. Magnetic resonance of imaging, computerized tomography, and myelography were performed to detect signs of delayed filling of the cysts. We performed a release of the valve and imbrication of the sacral cysts with laminectomies in 8 cases or recapping laminectomies in 4 cases. After surgery, symptoms improved in 10 (83%) of 12 patients, with an average follow-up of 27 months. Ten patients had sacral perineural cysts with signs of positive filling defect. Two (17%) of 12 patients experienced no significant improvement. In one of these patients, the filling defect was negative. In conclusion, a positive filling defect may become an indicator of good treatment outcomes.

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Blood loss and transfusion associated with musculoskeletal tumor surgery. 国際誌

Akira Kawai, Hiroaki Kadota, Umio Yamaguchi, Yuki Morimoto, Toshifumi Ozaki, Yasuo Beppu

Journal of surgical oncology 92 ( 1 ) 52 - 8 2005年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND OBJECTIVES: No organized data regarding the blood losses associated with musculoskeletal tumor surgery has been existed. The present study aimed to examine the extent of blood loss and the transfusion requirement associated with various kinds of musculoskeletal tumor surgeries in a large, well-defined sample. METHODS: The records of 1,047 consecutive operations for musculoskeletal tumors were reviewed. RESULTS: The total blood loss ranged from 0 to 26,050 ml (median: 95 ml). The operative time ranged from 5 to 1,140 min (median: 105 min). There was a significant correlation between the total blood loss and the operative time. The median blood loss was 10 ml in biopsies, 100 ml in curettages, 190 ml in amputations or disarticulations, 30 ml in marginal resections (bone tumors, 50 ml; soft tissue tumors, 25 ml), and 380 ml in wide resections (bone tumors, 2,155 ml; soft tissue tumors, 180 ml). Wide resections for malignant tumors were associated with significantly more blood loss than marginal resections for benign ones. Resections of bone tumors were accompanied by significantly more blood loss than those of soft tissue tumors. Overall, blood transfusions were required after 210 (20.1%) operations. CONCLUSIONS: Our results provide the first exhaustive data about blood loss and the subsequent need for transfusion associated with various kinds of musculoskeletal tumor surgeries that may be helpful for establishing a guideline for perioperative patient management.

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Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo. 国際誌

Tatsuo Ito, Mamoru Ouchida, Yuki Morimoto, Aki Yoshida, Yoshimi Jitsumori, Toshifumi Ozaki, Hiroshi Sonobe, Hajime Inoue, Kenji Shimizu

Cancer letters 224 ( 2 ) 311 - 9 2005年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

About 97% of synovial sarcomas harbor the SYT-SSX fusion gene by chromosomal translocation. We found that the histone deacetylase (HDAC) inhibitor FK228 significantly suppressed the growth of synovial sarcoma cells as compared with that of osteosarcoma. The 50% growth inhibition IC50 value we obtained for FK228 was 0.02-0.2 nM, and it indicates that its suppression effect on synovial sarcoma cells is the highest of any of the HDAC inhibitors yet reported. It was not likely that the growth suppression of FK228 depends on the doubling time of these cells. Introduction of SYT-SSX cDNA into HEK293 cells enhanced the sensitivity of the cells for FK228. Immunostaining of the FK228-treated cells using an anti-acetyl-histone H3 antibody showed that FK228 inhibits deacetylation of histone. In a mice assay, the growth of synovial sarcoma cells was markedly inhibited by FK228 treatment, and the invasion of tumors into surrounding tissues was suppressed. These results suggest that FK228 may be useful in developing therapeutic strategies to treat synovial sarcoma.

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Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

Akira Kawai, Toru Umeda, Takuro Wada, Koichiro Ihara, Kazuo Isu, Satoshi Abe, Takeshi Ishii, Hideshi Sugiura, Nobuhito Araki, Toshifumi Ozaki, Hiroo Yabe, Tadashi Hasegawa, Shoichiro Tsugane, Yasuo Beppu

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 10 ( 3 ) 258 - 63 2005年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

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.

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Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats. 国際誌

Shinya Arataki, Kazuhito Tomizawa, Akiyoshi Moriwaki, Keiichirou Nishida, Masayuki Matsushita, Toshifumi Ozaki, Toshiyuki Kunisada, Aki Yoshida, Hajime Inoue, Hideki Matsui

Journal of neurotrauma 22 ( 3 ) 398 - 406 2005年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Traumatic spinal cord injury (SCI) results in widespread neuronal cell death. Recent studies have suggested that activated calpain mediates neuronal cell death in the central nervous system. We conducted a study to determine whether calpain mediates neuronal cell death in the motor neurons of the spinal cord after SCI, and whether postinjury administration of the calpain inhibitors N-acetyl- Leu-Leu-Met-CHO (ALLM) and calpain inhibitor III (CI III) (MDL28170) reduces the motor disturbances in rats with a model of SCI. Adult male Wistar rats were subjected to SCI by application of a 20-g weight impactor probe to the spinal cord at T12 for 20 min. The rats were divided into three groups according to whether they were injected intravenously with 0.05-2.5 mg/kg ALLM, 10 mg/kg CI III, or 0.1% DMSO as a control every 24 h for 1 week after SCI. Calpain was activated in the spinal cord at 8 h, 24 h, and 5 days after SCI, and administration of ALLM inhibited its activation. ALLM, as compared to the DMSO vehicle alone, also significantly reduced the number of motor neurons in spinal-cord lesions that were positively labeled at 24 h after SCI with the terminal deoxynucleotidyl transferase-uridine nucleotide end-labeling (TUNEL) technique. Additionally, both the inclined plane test and footprint analysis showed markedly better motor activity after 4 weeks in rats injected with ALLM or CI III than in rats given vehicle only. These results suggest that activation of calpain plays a critical role in the neuronal cell death that follows SCI, and that calpain inhibitors may have benefit in treating the motor disturbances that follow SCI.

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Hoechst 33342は関節軟骨修復の長期研究において細胞標識物質として有用である

川崎啓介, 杉原進介, 大塚愛二, 西田圭一郎, 尾崎敏文, 吉田晶, 井上一

移植 40 ( 1 ) 78 - 79 2005年2月

下腿の悪性軟部腫ようの治療成績

中田英二, 尾崎敏文, 国定俊之, 大畑範英, 中川寧子

中部日本整形外科災害外科学会雑誌 48 ( 1 ) 109 - 110 2005年

滑膜性骨軟骨腫症の治療成績

中田英二, 尾崎敏文, 国定俊之

中部日本整形外科災害外科学会雑誌 48 ( 6 ) 989 - 990 2005年

腱鞘巨細胞腫の治療成績

井谷智, 尾崎敏文, 国定俊之, 中田英二, 橋詰博行

中部日本整形外科災害外科学会雑誌 48 ( 6 ) 981 - 982 2005年

SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex. 国際誌

Tatsuo Ito, Mamoru Ouchida, Sachio Ito, Yoshimi Jitsumori, Yuki Morimoto, Toshifumi Ozaki, Akira Kawai, Hajime Inoue, Kenji Shimizu

Laboratory investigation; a journal of technical methods and pathology 84 ( 11 ) 1484 - 90 2004年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Synovial sarcomas are soft-tissue tumors predominantly affecting children and young adults. They are molecular-genetically characterized by the SYT-SSX fusion gene generated from chromosomal translocation t(X; 18) (p11.2; q11.2). When we screened new gene products that interact with SYT or SSX proteins by yeast two-hybrid assay, we found that mSin3A, a component of the histone deacetylase complex, interacts with SYT but not with SSX. These results were confirmed by mammalian two-hybrid and pull-down assays. Analyses with sequential truncated proteins revealed a main mSin3A-interaction region on the SYT amino-terminal 93 amino acids, and another one on the region between 187th amino acid and break point. In luciferase assay, mSin3A repressed the transcriptional activity of reporter promoter mediated by SYT and hBRM/BRG1. Our results suggest that the histone deacetylase complex containing mSin3A may regulate the transcriptional activation mediated by SYT.

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滑膜肉腫におけるSYT-SSX蛋白結合因子の解析

大内田守, 伊藤達男, 尾崎敏文, 伊藤佐智夫, 大畑範英, 吉田晶, 清水憲二

日本癌学会総会記事 63回 370 - 370 2004年9月

Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute. 国際誌

Kazunori Ida, Satoshi Kawaguchi, Yuriko Sato, Tomohide Tsukahara, Yuki Nabeta, Hiroeki Sahara, Hideyuki Ikeda, Toshihiko Torigoe, Shingo Ichimiya, Kenjiro Kamiguchi, Takuro Wada, Satoshi Nagoya, Hiroaki Hiraga, Akira Kawai, Takeshi Ishii, Nobuhito Araki, Akira Myoui, Seiichi Matsumoto, Toshifumi Ozaki, Hideki Yoshikawa, Toshihiko Yamashita, Noriyuki Sato

Journal of immunology (Baltimore, Md. : 1950) 173 ( 2 ) 1436 - 43 2004年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24(+) synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24(+) synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24(+) synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.

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