研究者詳細 - 國定　俊之

Empowering pediatric, adolescent, and young adult patients with cancer utilizing generative AI chatbots to reduce psychological burden and enhance treatment engagement: a pilot study

Joe Hasei, Mana Hanzawa, Akihito Nagano, Naoko Maeda, Shinichirou Yoshida, Makoto Endo, Nobuhiko Yokoyama, Motoharu Ochi, Hisashi Ishida, Hideki Katayama, Tomohiro Fujiwara, Eiji Nakata, Ryuichi Nakahara, Toshiyuki Kunisada, Hirokazu Tsukahara, Toshifumi Ozaki

Frontiers in Digital Health 7 2025年2月

掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers Media SA

Background

Pediatric and adolescent/young adult (AYA) cancer patients face profound psychological challenges, exacerbated by limited access to continuous mental health support. While conventional therapeutic interventions often follow structured protocols, the potential of generative artificial intelligence (AI) chatbots to provide continuous conversational support remains unexplored. This study evaluates the feasibility and impact of AI chatbots in alleviating psychological distress and enhancing treatment engagement in this vulnerable population.

Methods

Two age-appropriate AI chatbots, leveraging GPT-4, were developed to provide natural, empathetic conversations without structured therapeutic protocols. Five pediatric and AYA cancer patients participated in a two-week intervention, engaging with the chatbots via a messaging platform. Pre- and post-intervention anxiety and stress levels were self-reported, and usage patterns were analyzed to assess the chatbots’ effectiveness.

Results

Four out of five participants reported significant reductions in anxiety and stress levels post-intervention. Participants engaged with the chatbot every 2–3 days, with sessions lasting approximately 10 min. All participants noted improved treatment motivation, with 80% disclosing personal concerns to the chatbot they had not shared with healthcare providers. The 24/7 availability particularly benefited patients experiencing nighttime anxiety.

Conclusions

This pilot study demonstrates the potential of generative AI chatbots to complement traditional mental health services by addressing unmet psychological needs in pediatric and AYA cancer patients. The findings suggest these tools can serve as accessible, continuous support systems. Further large-scale studies are warranted to validate these promising results.

DOI： 10.3389/fdgth.2025.1543543

Radiographic and Clinical Assessment of Unidirectional Porous Beta-Tricalcium Phosphate to Treat Benign Bone Tumors. 国際誌

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Takanao Kurozumi, Teruhiko Ando, Toshifumi Ozaki

Biomimetics (Basel, Switzerland) 10 ( 2 ) 2025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 evaluate radiographic changes, clinical outcomes, and complications following unidirectional porous beta-tricalcium phosphate (UDPTCP) implantation for the treatment of benign bone tumors. We retrospectively analyzed 46 patients who underwent intralesional resection. The patients were divided into two cohorts: Cohort 1 (n = 32), which included all bones except the phalanges and metacarpal/tarsal bones, and Cohort 2 (n = 14), which included the phalanges and metacarpal/tarsal bones. Radiographic changes were assessed at each reading based on resorption of the implanted UDPTCP and bone trabeculation through the defect. UDPTCP resorption and bone trabeculation were observed on radiographs within 3 months of surgery in all patients. Bone remodeling in the cavity progressed steadily for up to 3 years postoperatively. In Cohort 1, resorption and trabeculation progressed significantly in young patients, and trabeculation developed significantly in small lesions. The rates of resorption and trabeculation at 3 months postoperatively correlated statistically with their increased rates at one year. There was no statistical difference in resorption and trabeculation rates between Cohort 1 and Cohort 2. There were no cases of postoperative deep infections or allergic reactions related to the implant. UDPTCP is a useful bone-filling substitute for the treatment of benign bone tumors and has a low complication rate.

DOI： 10.3390/biomimetics10020101

Clinicopathological background of local recurrence in high grade sarcoma of the extremity with preoperative chemotherapy: a supplementary analysis of JCOG0304. 国際誌

Satoshi Tsukushi, Kazuhiro Tanaka, Toshiyuki Kunisada, Ryunosuke Machida, Satoshi Takenaka, Akira Kawai, Hirohisa Katagiri, Masanobu Takeyama, Makoto Endo, Katsuhiro Hayashi, Robert Nakayama, Hiroshi Hatano, Makoto Emori, Shinichirou Yoshida, Toshio Kojima, Akio Sakamoto, Jungo Imanishi, Ryosuke Kita, Toshifumi Ozaki, Yukihide Iwamoto

Japanese journal of clinical oncology 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial. METHODS: A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT. RESULTS: Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%-14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33-66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases. CONCLUSION: Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.

DOI： 10.1093/jjco/hyaf027

The Three-Class Annotation Method Improves the AI Detection of Early-Stage Osteosarcoma on Plain Radiographs: A Novel Approach for Rare Cancer Diagnosis. 国際誌

Joe Hasei, Ryuichi Nakahara, Yujiro Otsuka, Yusuke Nakamura, Kunihiro Ikuta, Shuhei Osaki, Tamiya Hironari, Shinji Miwa, Shusa Ohshika, Shunji Nishimura, Naoaki Kahara, Aki Yoshida, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

Cancers 17 ( 1 ) 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited.

DOI： 10.3390/cancers17010029

Study protocol: randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs. immediate surgery and adjuvant chemotherapy for localized soft tissue sarcoma: Japan Clinical Oncology Group study JCOG2102 (NACLESS). 国際誌

Yuki Funauchi, Satoshi Tsukushi, Hiroaki Hiraga, Akio Sakamoto, Toshiyuki Kunisada, Akihito Nagano, Koji Hiraoka, Kazutaka Kikuta, Tsukasa Yonemoto, Keisuke Ae, Akira Kawai, Makoto Endo, Yusuke Sano, Ryunosuke Machida, Tetsuya Sekita, Haruhiko Fukuda, Yoshinao Oda, Toshifumi Ozaki, Kazuhiro Tanaka

Japanese journal of clinical oncology 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The optimal timing of surgery and the number of courses of perioperative chemotherapy for high-risk soft tissue sarcoma patients are still controversial. Tumour growth during neoadjuvant chemotherapy led to limb amputation in some patients. This study aims to confirm the non-inferiority of surgery and three courses of adjuvant chemotherapy with adriamycin (30 mg/m2, days 1 and 2) plus ifosfamide (2 g/m2, days 1-5) compared with our standard treatment of three courses of neoadjuvant chemotherapy and surgery followed by two courses of adjuvant chemotherapy with adriamycin plus ifosfamide for localized high-risk soft tissue sarcoma patients. This is a multi-center, two-arm, open-label, randomized phase III trial. The primary aim is to confirm the non-inferiority in overall survival (margin: hazard ratio of 1.61). This is the first randomized controlled trial to compare neoadjuvant chemotherapy and immediate surgery for soft tissue sarcoma. This trial was initiated on 16 November 2022 and registered with the Japan Clinical Trials Registry (jRCTs031220446).

DOI： 10.1093/jjco/hyae160

がん遺伝子パネルによるfusion gene同定の診断的意義

中田英二, 國定俊之, 板野拓人, 片山晴喜, 安藤輝彦, 藤原智洋, 尾崎敏文

中国・四国整形外科学会雑誌 36 ( 3 ) 361 - 361 2024年10月

AIとメタバースを用いた骨軟部腫瘍診療革命早期診断から患者支援まで

長谷井嬢, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本癌治療学会学術集会抄録集 62回 PSP14 - 4 2024年10月

Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma. 国際誌

Koji Uotani, Tomohiro Fujiwara, Koji Ueda, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Yusuke Yoshioka, Takahiro Ochiya, Toshifumi Ozaki

Cancer science 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

DOI： 10.1111/cas.16343

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. 国際誌

Koji Demiya, Hiroshi Tazawa, Hiroya Kondo, Miho Kure, Yusuke Mochizuki, Tadashi Komatsubara, Aki Yoshida, Koji Uotani, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Molecular therapy. Oncology 32 ( 3 ) 200845 - 200845 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

DOI： 10.1016/j.omton.2024.200845

High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis. 国際誌

Joe Hasei, Ryuichi Nakahara, Yujiro Otsuka, Yusuke Nakamura, Tamiya Hironari, Naoaki Kahara, Shinji Miwa, Shusa Ohshika, Shunji Nishimura, Kunihiro Ikuta, Shuhei Osaki, Aki Yoshida, Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki

Cancer science 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

DOI： 10.1111/cas.16330

肉腫におけるゲノム医療の進歩 C-CATデータを用いた肉腫のゲノム解析

悪性末梢神経鞘腫瘍における悪性化を促進する新規メカニズム転写因子PRRX1とTOP2Aのタンパク質間相互作用の発見

たき平将太, 山田大祐, 大曽根達則, 高尾知佳, 板野拓人, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 98 ( 8 ) S1957 - S1957 2024年9月

中田英二, 遠西大輔, 二宮貴一朗, 山本英喜, 冨田秀太, 国定俊之, 藤原智洋, 二川摩周, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 98 ( 8 ) S1727 - S1727 2024年9月

Efficacy and safety of denosumab de‑escalation in giant cell tumor of bone. 国際誌

Eiji Nakata, Toshiyuki Kunisada, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Oncology letters 28 ( 2 ) 387 - 387 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Giant cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor. Denosumab has shown effectiveness in GCTB treatment; however, the benefits of denosumab de-escalation for unresectable GCTB have not been well discussed. The present study investigated the efficacy and safety of denosumab de-escalation for GCTB. The medical records of 9 patients with unresectable GCTB or resectable GCTB not eligible for resection, who received de-escalated denosumab treatment at Okayama University Hospital (Okayama, Japan) between April 2014 and December 2021, were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12 and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the re-ossification of osteolytic lesions obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. During the 24-weekly treatment, 2 patients remained stable, while 2 patients developed local recurrence. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. There were severe adverse events including osteonecrosis of the jaw (2 patients), atypical femoral fracture (1 patient) and malignant transformation of GCTB (1 patient). In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment. A 24-weekly treatment can also be administered, with careful attention paid to detecting local recurrence.

DOI： 10.3892/ol.2024.14520

Utilizing the Metaverse to Provide Innovative Psychosocial Support for Pediatric, Adolescent, and Young Adult Patients with Rare Cancer

Joe Hasei, Hisashi Ishida, Hideki Katayama, Naoko Maeda, Akihito Nagano, Motoharu Ochi, Masako Okamura, Shintaro Iwata, Kunihiro Ikuta, Shinichirou Yoshida, Tomohiro Fujiwara, Eiji Nakata, Ryuichi Nakahara, Toshiyuki Kunisada, Toshifumi Ozaki

Cancers 16 ( 15 ) 2617 - 2617 2024年7月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

This study investigated the potential of the metaverse in providing psychological support for pediatric and AYA cancer patients, with a focus on those with rare cancers. The research involved ten cancer patients and survivors from four distinct regions in Japan, who participated in metaverse sessions using customizable avatars, facilitating interactions across geographical and temporal barriers. Surveys and qualitative feedback were collected to assess the psychosocial impact of the intervention. The results demonstrated that the metaverse enabled patients to connect with peers, share experiences, and receive emotional support. The anonymity provided by avatars helped reduce appearance-related anxiety and stigma associated with cancer treatment. A case study of a 19-year-old male with spinal Ewing’s sarcoma highlighted the profound emotional relief fostered by metaverse interactions. The findings suggest that integrating virtual spaces into healthcare models can effectively address the unique needs of pediatric and AYA cancer patients, offering a transformative approach to delivering psychosocial support and fostering a global patient community. This innovative intervention has the potential to revolutionize patient care in the digital age.

DOI： 10.3390/cancers16152617

軟部肉腫患者における治療前全身状態と運動機能は生存予後および合併症の発生に関連するか

悪性末梢神経鞘腫瘍におけるPRRX1とTOP2Aの相互作用による悪性化メカニズムの新規解明

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1529 - S1529 2024年6月

下腿軟部肉腫切除術後の機能低下リスク因子の検討

板野拓人, 中田英二, 片山晴喜, 近藤彩奈, 黒住尭巨, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1517 - S1517 2024年6月

周術期がん患者のロコモ併存率の検討

堅山佳美, 中田英二, 明崎禎輝, 近藤彩奈, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1501 - S1501 2024年6月

近藤彩奈, 藤原智洋, 堅山佳美, 黒住尭巨, 板野拓人, 片山晴喜, 濱田全紀, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1501 - S1501 2024年6月

骨・軟部腫瘍の基礎研究の新展開骨・軟部肉腫に対する全身治療および局所治療の新規治療モダリティーの創出を目指して

藤原智洋, 近藤彩奈, 福岡史朗, 吉田晶, 大島修吾, 黒住尭巨, 板野拓人, 片山晴喜, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1463 - S1463 2024年6月

加速する骨・軟部腫瘍に対するゲノム医療: 現状と課題肉腫におけるゲノム医療の現状と課題

中田英二, 遠西大輔, 二宮貴一朗, 山本英喜, 冨田秀太, 藤原智洋, 国定俊之, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1457 - S1457 2024年6月

骨・軟部肉腫に対する腫瘍用人工関節再建後に深部感染を起こした症例の検討

片山晴喜, 中田英二, 黒住尭巨, 板野拓人, 近藤彩奈, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1623 - S1623 2024年6月

神経線維腫症1型を中心とした遺伝性骨・軟部腫瘍に対する専門外来の有用性

中田英二, 二川摩周, 平沢晃, 山本英喜, 国定俊之, 板野拓人, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1614 - S1614 2024年6月

骨肉腫患者における肉腫専門病院受診前因子の実態調査生命予後の改善を目指す"4-week ruleの提言"

黒住尭巨, 藤原智洋, 板野拓人, 片山晴喜, 近藤彩奈, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1607 - S1607 2024年6月

多職種から見た骨・軟部腫瘍治療の現状と課題肉腫発生ハイリスク患者に対する遺伝性骨・軟部腫瘍外来の取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1579 - S1579 2024年6月

多職種から見た骨・軟部腫瘍治療の現状と課題肉腫発生ハイリスク患者に対する遺伝性骨・軟部腫瘍外来の取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1579 - S1579 2024年6月

神経線維腫症1型を中心とした遺伝性骨・軟部腫瘍に対する専門外来の有用性

中田英二, 二川摩周, 平沢晃, 山本英喜, 国定俊之, 板野拓人, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1614 - S1614 2024年6月

加速する骨・軟部腫瘍に対するゲノム医療: 現状と課題肉腫におけるゲノム医療の現状と課題

中田英二, 遠西大輔, 二宮貴一朗, 山本英喜, 冨田秀太, 藤原智洋, 国定俊之, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1457 - S1457 2024年6月

Clinical Application of Unidirectional Porous Hydroxyapatite to Bone Tumor Surgery and Other Orthopedic Surgery. 国際誌

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Toshiaki Hata, Kohei Sato, Haruyoshi Katayama, Ayana Kondo, Toshifumi Ozaki

Biomimetics (Basel, Switzerland) 9 ( 5 ) 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Unidirectional porous hydroxyapatite (UDPHAp) was developed as a remarkable scaffold characterized by a distinct structure with unidirectional pores oriented in the horizontal direction and connected through interposes. We evaluated the radiographic changes, clinical outcomes, and complications following UDPHAp implantation for the treatment of bone tumors. Excellent bone formation within and around the implant was observed in all patients treated with intralesional resection and UDPHAp implantation for benign bone tumors. The absorption of UDPHAp and remodeling of the bone marrow space was observed in 45% of the patients at a mean of 17 months postoperatively and was significantly more common in younger patients. Preoperative cortical thinning was completely regenerated in 84% of patients at a mean of 10 months postoperatively. No complications related to the implanted UDPHAp were observed. In a pediatric patient with bone sarcoma, when the defect after fibular resection was filled with UDPHAp implants, radiography showed complete resorption of the implant and clear formation of cortex and marrow in the resected part of the fibula. The patient could walk well without crutches and participate in sports activities. UDPHAp is a useful bone graft substitute for the treatment of benign bone tumors, and the use of this material has a low complication rate. We also review and discuss the potential of UDPHAp as a bone graft substitute in the clinical setting of orthopedic surgery.

DOI： 10.3390/biomimetics9050294

p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression.

Tadashi Komatsubara, Hiroshi Tazawa, Joe Hasei, Toshinori Omori, Kazuhisa Sugiu, Yusuke Mochizuki, Koji Demiya, Aki Yoshida, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Acta medica Okayama 78 ( 2 ) 151 - 161 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

DOI： 10.18926/AMO/66924

PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. 国際誌

Shota Takihira, Daisuke Yamada, Tatsunori Osone, Tomoka Takao, Masakiyo Sakaguchi, Michiyuki Hakozaki, Takuto Itano, Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Takeshi Takarada

British journal of cancer 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

DOI： 10.1038/s41416-024-02632-8

Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors. 国際誌

Haruyoshi Katayama, Atsushi Fujimura, Rongsheng Huang, Yusuke Otani, Takuto Itano, Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki

Cancer science 115 ( 3 ) 871 - 882 2024年3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 malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST.

DOI： 10.1111/cas.16077

悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024年3月

肉腫におけるがん遺伝子パネルによるfusion gene同定の意義

中田英二, 藤原智洋, 板野拓人, 片山晴喜, 二川摩周, 山元英崇, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1246 - S1246 2024年3月

AIとDXを用いた骨・軟部腫瘍診療への新たな挑戦

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1371 - S1371 2024年3月

悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024年3月

術前がん患者の各ロコモ度テストにおける関連因子

堅山佳美, 中田英二, 近藤彩奈, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 98 ( 3 ) S1321 - S1321 2024年3月

遺伝性骨・軟部腫瘍外来における肉腫発生at-risk者への取り組み

二川摩周, 中田英二, 山本英喜, 深野智華, 加藤芙美乃, 大住理沙, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 25 - 25 2024年2月

Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus. 国際誌

Koji Uotani, Hiroshi Tazawa, Joe Hasei, Tomohiro Fujiwara, Aki Yoshida, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Hiroya Kondo, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiaki Hata, Toshiyuki Kunisada, Ken Takeda, Yasuo Urata, Toshiyoshi Fujiwara, Toshifumi Ozaki

PloS one 19 ( 2 ) e0298292 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

DOI： 10.1371/journal.pone.0298292

【がん時代の整形外科必携! 骨転移診療アップデート】骨転移治療総論骨転移におけるロコモティブシンドローム

中田英二, 堅山佳美, 明崎禎輝, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

臨床整形外科 58 ( 12 ) 1431 - 1438 2023年12月

記述言語：日本語出版者・発行元：(株)医学書院

＜文献概要＞がんは高齢者に多いため,ロコモティブシンドロームが発生しやすい.がんの切除を行う患者の約9割は,ロコモを合併している.したがって,がん患者では,適切ながんロコモのスクリーニングが重要である.また,最近,がん治療は外来に移行しつつあり,がん患者が日常生活動作を維持することが求められ,がんロコモ予防に対する社会のニーズが増えている.したがって,各施設において,診療科横断的にがんロコモ予防に取り組む体制を構築することが重要である.

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01554&link_issn=&doc_id=20231129020009&doc_link_id=10.11477%2Fmf.1408202843&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408202843&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Factors associated with survival in patients with clear cell sarcoma. 国際誌

Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Toshiharu Mitsuhashi, Toshifumi Ozaki, Akira Kawai

The bone & joint journal 105-B ( 11 ) 1216 - 1225 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. METHODS: The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. RESULTS: The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). CONCLUSION: Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

DOI： 10.1302/0301-620X.105B11.BJJ-2022-0743.R3

著明な疼痛を伴う椎間板発生の仙骨脊索腫の一例

藤原智洋, 魚谷弘二, 国定俊之, 中田英二, 小田孔明, 三澤治夫, 尾崎敏文

中国・四国整形外科学会雑誌 35 ( 3 ) 423 - 423 2023年11月

【整形外科外来Red Flags 2023】脊椎転移におけるRed Flags

中田英二, 藤原智洋, 国定俊之, 尾崎敏文

Orthopaedics 36 ( 10 ) 69 - 80 2023年10月

記述言語：日本語出版者・発行元：(株)全日本病院出版会

椎体転移では腫瘍が増大すると腫瘍が直接神経を圧迫したり,椎体圧潰により脊髄が圧迫され,知覚障害や運動麻痺が生じることがある.ほとんどの骨転移患者は,麻痺が発生する前に脊椎転移部に痛みを自覚している.したがって,痛みは麻痺の危険信号であり,脊椎転移部に痛みが出現した場合,早急に治療を開始することが重要である.麻痺を予防するために,最も基本的で重要な対処法は,脊椎転移部に痛みが出現した場合,脊椎SREsの発生も考え,早急に画像検査を行い,痛みの原因と考えられる著しい椎体破壊や脊髄圧迫を認めた場合,早急に治療(RTなど)を行うことである(Red Flag).なお,早急に画像検査が行えない場合,直近のCT等を見直し,椎体破壊の有無を確認すべきである.Red Flagに対して早急に対処し,麻痺が出現する前に治療が開始できれば,麻痺発生数を減らすことができる.(著者抄録)

骨軟部肉腫の全ゲノム、トランスクリプトーム解析(Whole genome and transcriptome analysis of bone and soft tissue sarcomas)

平井利英, 片山琴絵, 白石友一, 川井章, 吉田朗彦, 小林寛, 大津敬, 国定俊之, 西田佳弘, 吉田新一郎, 近藤格, 柴田龍弘, 井元清哉, 松田浩一, 平田真

日本癌学会総会記事 82回 384 - 384 2023年9月

Advances in treatment of alveolar soft part sarcoma: an updated review. 国際誌

Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Kenji Nishida, Hiroyuki Yanai, Tomoki Nakamura, Kazuhiro Tanaka, Toshifumi Ozaki

Japanese journal of clinical oncology 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.

DOI： 10.1093/jjco/hyad102

ヒトiPS細胞由来肢芽間葉系細胞を用いた骨再建法の開発

佐藤浩平, 高尾知佳, 中田英二, 藤澤佑樹, 山田大祐, 上原健敬, 藤原智洋, 依光正則, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 8 ) S1868 - S1868 2023年8月

血中CSF-1濃度は浸潤性軟部肉腫における腫瘍随伴マクロファージの浸潤と相関し生存予後と相関する

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1886 - S1886 2023年8月

肉腫細胞と肉腫微小環境の双方を標的とする複合治療の開発軟部肉腫に対する新しい治療アプローチ

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 板野拓人, 片山晴喜, 佐藤浩平, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1885 - S1885 2023年8月

MPNST腫瘍細胞内のカテコラミン合成経路の阻害ががん幹細胞性に与える影響と治療薬としての可能性

片山晴喜, 藤村篤史, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1884 - S1884 2023年8月

翻訳制御機構を標的とした横紋筋肉腫の新規治療法の開発

板野拓人, 中田英二, 藤村篤史, 黄栄生, 片山晴喜, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1884 - S1884 2023年8月

肉腫に対する微小環境改善薬の開発ナノキャリア修飾によるCSF-1/CSF-1R阻害剤の安全性の向上

藤原智洋, Yakoub Mohamed, 吉田晶, 近藤彩奈, 板野拓人, 片山晴喜, 中田英二, 国定俊之, 尾崎敏文, Ouerfelli Ouerthek, Healey John

日本整形外科学会雑誌 97 ( 8 ) S1892 - S1892 2023年8月

肉腫診療におけるがん遺伝子パネルの有用性

中田英二, 藤原智洋, 国定俊之, 遠西大輔, 山本英喜, 二宮貴一朗, 冨田秀太, 二川摩周, 平沢晃, 豊岡伸一, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1894 - S1894 2023年8月

Computer assisted orthopaedic surgeryがもたらす整形外科の次世代診療希少疾患に対するAI開発戦略

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1783 - S1783 2023年8月

テロメラーゼ依存性腫瘍融解アデノウイルスの骨・軟部腫瘍への応用を目指した蛍光タンパクによるウイルスの治療効果予測

魚谷弘二, 藤原智洋, 田澤大, 植田昌敬, 志渡澤央和, 小田孔明, 鉄永倫子, 三澤治夫, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1714 - S1714 2023年8月

テロメラーゼ依存性腫瘍融解アデノウイルスの骨・軟部腫瘍への応用を目指した蛍光タンパクによるウイルスの治療効果予測

魚谷弘二, 藤原智洋, 田澤大, 植田昌敬, 志渡澤央和, 小田孔明, 鉄永倫子, 三澤治夫, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1714 - S1714 2023年8月

翻訳制御機構を標的とした横紋筋肉腫の新規治療法の開発

板野拓人, 中田英二, 藤村篤史, 黄栄生, 片山晴喜, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1884 - S1884 2023年8月

ヒトiPS細胞由来肢芽間葉系細胞を用いた骨再建法の開発

佐藤浩平, 高尾知佳, 中田英二, 藤澤佑樹, 山田大祐, 上原健敬, 藤原智洋, 依光正則, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 8 ) S1868 - S1868 2023年8月

Computer assisted orthopaedic surgeryがもたらす整形外科の次世代診療希少疾患に対するAI開発戦略

たき平将太, 中田英二, 板野拓人, 片山晴喜, 藤原智洋, 国定俊之, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1890 - S1890 2023年8月

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1783 - S1783 2023年8月

前腕の軟部肉腫の治療成績

中田英二, 国定俊之, 藤原智洋, 片山晴喜, 板野拓人, 近藤彩奈, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1380 - S1380 2023年6月

骨・軟部腫瘍の教育と専門医育成骨・軟部腫瘍における基礎・トランスレーショナル研究の魅力

藤原智洋, 中田英二, 国定俊之, 川井章, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1302 - S1302 2023年6月

切除不能な骨巨細胞腫に対するデノスマブのde-escalation

片山晴喜, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1347 - S1347 2023年6月

周術期がん患者におけるがんロコモティブシンドローム

尾崎敏文, 堅山佳美, 濱田全紀, 国定俊之, 藤原智洋, 千田益生, 中田英二

運動器リハビリテーション 34 ( 2 ) 155 - 155 2023年6月

肉腫診療におけるゲノム医療

板野拓人, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1449 - S1449 2023年6月

骨盤悪性骨腫瘍に対する股関節包内切除術と包外切除術の腫瘍学的予後および機能的予後の比較検討

藤原智洋, Stevenson Jonathan, Parry Michael, Grimer Robert, 津田祐輔, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文, Jeys Lee

日本整形外科学会雑誌 97 ( 6 ) S1443 - S1443 2023年6月

小児骨・軟部腫瘍の治療:進歩と課題小児悪性骨腫瘍の再建の工夫と問題点

国定俊之, 中田英二, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1424 - S1424 2023年6月

高齢軟部肉腫患者において年代別で生存予後因子および合併症リスク因子は異なるか

近藤彩奈, 藤原智洋, 畑利彰, 板野拓人, 片山晴喜, 佐藤浩平, 吉田晶, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1465 - S1465 2023年6月

軟部肉腫患者における地理的因子の臨床的意義肉腫専門施設受診前因子の改善を目指して

畑利彰, 藤原智洋, 国定俊之, 中田英二, 近藤宏也, 佐藤浩平, 近藤彩奈, 片山晴喜, 板野拓人, 吉田晶, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1467 - S1467 2023年6月

悪性末梢神経鞘腫瘍における治療標的PRRX1の同定と新規創薬開発の可能性

たき平将太, 山田大祐, 岡本真幸, 高尾知佳, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 6 ) S1428 - S1428 2023年6月

MPNST腫瘍細胞内のカテコラミン合成経路とその腫瘍幹細胞性維持に対する役割

片山晴喜, 藤村篤史, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1493 - S1493 2023年6月

手術予定がん患者のロコモティブシンドロームと関連因子

堅山佳美, 中田英二, 濱田全紀, 国定俊之, 藤原智洋, 近藤彩奈, 千田益生, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1477 - S1477 2023年6月

肉腫診療におけるゲノム医療

板野拓人, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 6 ) S1449 - S1449 2023年6月

悪性末梢神経鞘腫瘍における治療標的PRRX1の同定と新規創薬開発の可能性

たき平将太, 山田大祐, 岡本真幸, 高尾知佳, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 6 ) S1428 - S1428 2023年6月

術前化学療法を併用した四肢高悪性度肉腫に対する局所再発の臨床病理学的背景 JCOG0304副次的解析

筑紫聡, 田仲和宏, 国定俊之, 町田龍之介, 竹中聡, 川井章, 片桐浩久, 比留間徹, 松本嘉寛, 土屋弘行, 中山ロバート, 畠野宏史, 江森誠人, 吉田新一郎, 大幸英至, 坂本昭夫, 今西淳悟, 喜多亮介, 尾崎敏文, 岩本幸英

日本整形外科学会雑誌 97 ( 6 ) S1459 - S1459 2023年6月

骨盤悪性骨腫瘍に対する股関節包内切除術と包外切除術の腫瘍学的予後および機能的予後の比較検討

藤原智洋, Stevenson Jonathan, Parry Michael, Grimer Robert, 津田祐輔, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文, Jeys Lee

日本整形外科学会雑誌 97 ( 6 ) S1443 - S1443 2023年6月

軟部肉腫に対する広範切除後の機能回復は成人患者と高齢患者でどのように異なるか? 下肢発生肉腫の検討

藤原智洋, 中田英二, 近藤彩奈, 堅山佳美, 濱田全紀, 国定俊之, 尾崎敏文, 千田益生

The Japanese Journal of Rehabilitation Medicine 60 ( 特別号 ) 3 - 3 2023年5月

軟部肉腫に対する広範切除後の機能回復は成人患者と高齢患者でどのように異なるか? 下肢発生肉腫の検討

藤原智洋, 中田英二, 近藤彩奈, 堅山佳美, 濱田全紀, 国定俊之, 尾崎敏文, 千田益生

The Japanese Journal of Rehabilitation Medicine 60 ( 特別号 ) 3 - 3 2023年5月

片側下腿に発生した多発性グロムス腫瘍の一例

徳田貴大, 藤原智洋, 近藤彩奈, 国定俊之, 中田英二, 西村碧フィリーズ, 柳井広之, 尾崎敏文

中国・四国整形外科学会雑誌 35 ( 1 ) 47 - 51 2023年4月

記述言語：日本語出版者・発行元：中国・四国整形外科学会

症例は21歳男性で、左下腿脛骨外側部のグロムス腫瘍切除術後2ヵ月経過した時点で左下腿の疼痛が再燃した。MRIでは左脛骨前面、脛骨後面、脛腓間、腓骨周囲に多発性の腫瘤を認め、これら全病変を辺縁切除した。病理検査では全てグロムス腫瘍と診断され、術後1年の時点で疼痛の再燃や腫瘍の再発は認めず、趣味のダンスも再開している。

Musculoskeletal Tumor 骨・軟部腫瘍骨・軟部腫瘍におけるがん遺伝子プロファイリング検査骨・軟部腫瘍診療におけるがん遺伝子パネルの役割

[Ⅲ. The Role of Comprehensive Genomic Profiling in Sarcoma].

Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Shinichi Toyooka, Daisuke Ennishi, Hideki Yamamoto, Kiichiro Ninomiya, Shuta Tomida, Akira Hirasawa, Mashu Futagawa, Masahiro Tabata

Gan to kagaku ryoho. Cancer & chemotherapy 50 ( 3 ) 314 - 320 2023年3月

中田英二, 藤原智洋, 国定俊之, 尾崎敏文, 豊岡伸一, 遠西大輔, 山本英喜, 二宮貴一朗, 冨田秀太, 平沢晃, 二川摩周, 田端雅弘

癌と化学療法 50 ( 3 ) 314 - 320 2023年3月

肉腫におけるがんゲノム医療の現状と未来がん遺伝子パネル検査から同定されるGermline Findingsへの対応

二川摩周, 中田英二, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S446 - S446 2023年3月

悪性末梢神経鞘腫瘍におけるPRRX1の治療標的分子としての可能性

たき平将太, 中田英二, 大曽根達則, 山田大祐, 高尾知佳, 佐藤浩平, 畑利彰, 藤原智洋, 国定俊之, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 97 ( 3 ) S1040 - S1040 2023年3月

がんロコモ診療の課題と展望周術期患者のがんロコモ・サルコペニア・フレイル

堅山佳美, 中田英二, 濱田全紀, 国定俊之, 藤原智洋, 千田益生, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S18 - S18 2023年3月

小児AYA世代骨軟部腫瘍の課題と対策遺伝性骨・軟部腫瘍外来の取り組み

中田英二, 藤原智洋, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 66 ( 春季学会 ) 58 - 58 2023年3月

骨軟部腫瘍診療のサステナビリティ原発性悪性骨腫瘍患者の居住地と診療施設間の地理的因子は予後と相関するか?米国の診療体制の現状と課題

藤原智洋, 中田英二, 国定俊之, 尾崎敏文, 小倉浩一, Healey John

中部日本整形外科災害外科学会雑誌 66 ( 春季学会 ) 54 - 54 2023年3月

骨・軟部腫瘍診療におけるデジタルトランスフォーメーションとプレシジョン・メディシン Liquid biopsyを用いた骨・軟部腫瘍診療におけるプレシジョン・メディシンへの期待と課題

藤原智洋, 中田英二, 畑利彰, 近藤彩奈, 板野拓人, 吉田晶, 片山晴喜, 佐藤浩平, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 3 ) S613 - S613 2023年3月

骨・軟部腫瘍診療におけるデジタルトランスフォーメーションとプレシジョン・メディシン AIを用いた骨肉腫X線読影における転移学習の効果

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 3 ) S611 - S611 2023年3月

肉腫におけるがんゲノム医療の現状と未来肉腫におけるがん遺伝子パネルの意義

中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S445 - S445 2023年3月

老年学的因子は浸潤性軟部肉腫患者の生存予後と相関するか

畑利彰, 藤原智洋, 柳井広之, 吉田晶, 板野拓人, 近藤彩奈, 片山晴喜, 佐藤浩平, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S80 - S80 2023年3月

前腕に発生した肉腫の治療成績

片山晴喜, 中田英二, 板野拓人, 近藤彩奈, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S321 - S321 2023年3月

高齢軟部肉腫患者において術後合併症の発生は生存予後に影響を与えるか

近藤彩奈, 藤原智洋, 吉田晶, 板野拓人, 片山晴喜, 佐藤浩平, 畑利彰, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S320 - S320 2023年3月

骨盤の悪性腫瘍を究める骨盤腫瘍に対する創外固定を併用したhip transposition法

国定俊之, 藤原智洋, 中田英二, 千田益生, 尾崎敏文

日本整形外科学会雑誌 97 ( 2 ) S437 - S437 2023年3月

骨巨細胞腫に対するデノスマブのde-escalationの有効性

板野拓人, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 97 ( 3 ) S959 - S959 2023年3月

悪性末梢神経鞘腫瘍におけるPRRX1の悪性化因子としての役割

たき平将太, 中田英二, 山田大祐, 片山晴喜, 畑利彰, 藤原智洋, 高尾知佳, 国定俊之, 宝田剛志, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 16 - 16 2023年2月

神経線維腫症1型における院内レジストリの構築と定期的なサーベイランスの実施

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 34 - 34 2023年2月

遺伝性骨・軟部腫瘍外来におけるNF-1の診療

中田英二, 二川摩周, 藤原智洋, 国定俊之, 山本英喜, 平沢晃, 尾崎敏文

日本レックリングハウゼン病学会学術大会プログラム・抄録集 14回 33 - 33 2023年2月

Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas 査読国際誌

Yoshinao Oda, Kazuhiro Tanaka, Takanori Hirose, Tadashi Hasegawa, Nobuyuki Hiruta, Masanori Hisaoka, Masato Yoshimoto, Hiroshi Otsuka, Hirofumi Bekki, Takeaki Ishii, Makoto Endo, Toshiyuki Kunisada, Toru Hiruma, Hiroyuki Tsuchiya, Hirohisa Katagiri, Yoshihiro Matsumoto, Akira Kawai, Robert Nakayama, Hiroyuki Kawashima, Satoshi Takenaka, Makoto Emori, Munenori Watanuki, Yukihiro Yoshida, Takeshi Okamoto, Junki Mizusawa, Haruhiko Fukuda, Toshifumi Ozaki, Yukihide Iwamoto, Takayuki Nojima

BMC Cancer 22 ( 1 ) 94 - 94 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

<title>Abstract</title><sec>
<title>Background</title>
Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis.

</sec><sec>
<title>Methods</title>
Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board.

</sec><sec>
<title>Results</title>
A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (<italic>κ</italic>) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the <italic>p</italic>-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893–18.188, <italic>p</italic> = 0.070).

</sec><sec>
<title>Conclusion</title>
The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted <italic>κ</italic> score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO.

</sec><sec>
<title>Trial registration</title>
UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

</sec>

DOI： 10.1186/s12885-022-09195-y

その他リンク： https://link.springer.com/article/10.1186/s12885-022-09195-y/fulltext.html

Five cases of atypical ulnar fractures associated with long-term bisphosphonate use: An anatomical and mechanical analysis using a finite element model

Shunji Okita, Taichi Saito, Norio Yamamoto, Yusuke Mochizuki, Ryuichi Nakahara, Yasunori Shimamura, Toshiyuki Kunisada, Keiichiro Nishida, Toshifumi Ozaki

Journal of Orthopaedic Science 2022年11月

骨転移,肺転移を来たした基底細胞癌の1例

浦上仁志, 加持達弥, 山崎修, 山田潔, 黒住和彦, 国定俊之, 田端雅弘, 森実真

西日本皮膚科 84 ( 5 ) 443 - 446 2022年10月

記述言語：日本語出版者・発行元：日本皮膚科学会-西部支部

59歳,女性。初診の9年前より前頭部右側に徐々に増大する硬化性局面を認めた。限局性強皮症と考えられ経過観察されていたが,同部位に潰瘍を生じ皮膚生検にて基底細胞癌と診断された。下床の頭蓋骨を含めて広範囲切除し,前外側大腿遊離皮弁による再建術を施行した。病理組織学的所見では斑状強皮症型/破壊型であり,頭蓋骨内部への浸潤が認められた。切除断端陰性であったが,約半年後に第5胸椎左横突起転移を生じ切除術を施行した。その約1年後右大腿骨内側顆に転移が出現し,切除・人工関節置換術後にシスプラチン・ドキソルビシン療法を施行した。その約2年後,右肺門部転移が出現しカルボプラチン・パクリタキセル療法を施行した。その後,特発性器質化肺炎を生じたため化学療法を中止し,プレドニゾロン投与にて加療した。その後は化学療法の再開を希望されなかったため,緩和的放射線療法を施行した。(著者抄録)

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01003&link_issn=&doc_id=20221110410016&doc_link_id=10.2336%2Fnishinihonhifu.84.443&url=https%3A%2F%2Fdoi.org%2F10.2336%2Fnishinihonhifu.84.443&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

軟部肉腫に対する薬物療法がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 国定俊之, 平沢晃, 遠西大輔, 尾崎敏文

中部日本整形外科災害外科学会雑誌 65 ( 秋季学会 ) 77 - 77 2022年10月

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022年10月

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022年10月

下肢長幹骨発生の原発性悪性骨腫瘍に対する広範切除術後の機能回復は再建法によりどのように異なるか?

藤原智洋, 中田英二, 堅山佳美, 濱田全紀, 国定俊之, 尾崎敏文, 千田益生

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S364 - S364 2022年10月

骨盤悪性腫瘍に対するHip transposition法の術後機能・歩行能力

国定俊之, 中田英二, 藤原智洋, 尾崎敏文, 堅山佳美, 濱田全紀, 千田益生

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S364 - S364 2022年10月

60歳以上の術前がん患者のがんロコモとサルコペニア,フレイルの有病率

堅山佳美, 中田英二, 藤原智洋, 國定俊之, 濱田全紀, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S363 - S363 2022年10月

がんロコモを予防するための骨転移患者のマネージメントデータに基づく骨転移診療

中田英二, 濱田全紀, 国定俊之, 藤原智洋, 堅山佳美, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 59 ( 秋季特別号 ) S322 - S322 2022年10月

小児固形腫瘍における基礎・トランスレーショナル研究の現状と展望骨軟部肉腫における基礎・トランスレーショナル研究の現状と展望

藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本小児血液・がん学会雑誌 59 ( 4 ) 169 - 169 2022年10月

片側下腿に発生した多発性グロムス腫瘍の一例

徳田貴大, 藤原智洋, 国定俊之, 中田英二, 尾崎敏文

中国・四国整形外科学会雑誌 34 ( 3 ) 395 - 395 2022年10月

骨・軟部肉腫に対するがんゲノムプロファイリング検査から検出されるpresumed germline pathogenic variantsの意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1770 - S1770 2022年9月

骨・軟部腫瘍の基礎科学のトピックスクリニカルシークエンスによる肉腫のゲノム医療

中田英二, 藤原智洋, 国定俊之, 二川摩周, 遠西大輔, 久保寿夫, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1533 - S1533 2022年9月

AIと診断・治療 AIによる骨肉腫X線読影システムの偽陽性対策

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1741 - S1741 2022年9月

Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy. 国際誌

Eiji Nakata, Hotaka Kawai, Tomohiro Fujiwara, Toshiyuki Kunisada, Hirofumi Inoue, Mashu Futagawa, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Oncology letters 24 ( 3 ) 319 - 319 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high-grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon-ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow-up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

DOI： 10.3892/ol.2022.13439

Cathepsin proteaseは浸潤型軟部肉腫における浸潤性発育および生存予後に相関する

悪性軟部腫瘍に対する抗CSF-1R阻害薬の有効性抗腫瘍効果と微小環境へ与える影響(Antitumor effect of CSF-1/CSF-1R blockade in soft-tissue sarcomas)

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 近藤宏也, 国定俊之, 尾崎敏文

日本癌学会総会記事 81回 J - 1062 2022年9月

藤原智洋, Zhang Lingxin, Chandler Andrew, Yakoub Mohamed, 中田英二, 国定俊之, 尾崎敏文, Hameed Meera, Healey John

日本整形外科学会雑誌 96 ( 8 ) S1769 - S1769 2022年9月

軟部肉腫に対する抗CSF-1R阻害薬の有効性抗腫瘍効果と微小環境へ与える影響

たき平将太, 山田大祐, 高尾知佳, 中田英二, 近藤宏也, 佐藤浩平, 畑利彰, 藤原智洋, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 96 ( 8 ) S1768 - S1768 2022年9月

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 近藤宏也, 片山晴喜, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1765 - S1765 2022年9月

骨・軟部腫瘍の基礎科学のトピックス転移性骨肉腫は臓器指向性サイトカインの分泌を介して微小環境を変化させ前転移ニッチを形成する

近藤宏也, 田澤大, 藤原智洋, 近藤彩奈, 片山晴喜, 佐藤浩平, 畑利彰, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1532 - S1532 2022年9月

MPNSTの癌幹細胞性維持に対する腫瘍内のアドレナリン合成酵素の役割

片山晴喜, 藤村篤史, 中田英二, 大谷悠介, 藤原智洋, 国定俊之, 神谷厚範, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1768 - S1768 2022年9月

腫瘍随伴マクロファージの浸潤割合および予後を予測する血中バイオマーカーの特定浸潤性軟部肉腫患者における検討

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 近藤宏也, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 箱崎道之, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1766 - S1766 2022年9月

浸潤型軟部肉腫におけるCathepsin Proteaseの発現の臨床病理学的意義(Clinicopathological significance of cathepsin protease expression in infiltrative soft-tissue sarcomas)

藤原智洋, Zhang Lingxin, Chandler Andrew, Yakoub Mohamed, Hameed Meera, 中田英二, 国定俊之, 尾崎敏文, Healey John

日本癌学会総会記事 81回 P - 1275 2022年9月

浸潤性軟部肉腫患者における腫瘍随伴マクロファージの浸潤および予後を予測する血中バイオマーカーの特定(Circulating cytokines as blood biomarker predictive of TAM infiltration and prognosis in patients with infiltrative STS)

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 近藤宏也, 国定俊之, 尾崎敏文

日本癌学会総会記事 81回 J - 1065 2022年9月

AIと診断・治療 AIによる骨肉腫X線読影システムの偽陽性対策

長谷井嬢, 中原龍一, 藤原智洋, 中田英二, 国定俊之, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1741 - S1741 2022年9月

転移性骨肉腫細胞はCCL2によるM2マクロファージの腫瘍内浸潤を誘導して肺転移を促進する(Metastatic osteosarcoma cells facilitate lung metastasis by inducing CCL2-mediated tumor infiltration of M2 macrophages)

近藤宏也, 田澤大, 久禮美穂, 藤原智洋, 国定俊之, 尾崎敏文, 藤原俊義

日本癌学会総会記事 81回 J - 2087 2022年9月

がんゲノム医療において遺伝性骨・軟部肉腫を同定する臨床的意義(Clinical significance of identifying hereditary bone and soft tissue sarcomas in precision medicine)

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 植野さやか, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本癌学会総会記事 81回 P - 3121 2022年9月

がんゲノム医療において遺伝性骨・軟部肉腫を同定する臨床的意義(Clinical significance of identifying hereditary bone and soft tissue sarcomas in precision medicine)

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 植野さやか, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本癌学会総会記事 81回 P - 3121 2022年9月

骨・軟部肉腫に対するがんゲノムプロファイリング検査から検出されるpresumed germline pathogenic variantsの意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1770 - S1770 2022年9月

骨・軟部腫瘍の基礎科学のトピックスクリニカルシークエンスによる肉腫のゲノム医療

中田英二, 藤原智洋, 国定俊之, 二川摩周, 遠西大輔, 久保寿夫, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1533 - S1533 2022年9月

骨・軟部腫瘍の基礎科学のトピックス転移性骨肉腫は臓器指向性サイトカインの分泌を介して微小環境を変化させ前転移ニッチを形成する

近藤宏也, 田澤大, 藤原智洋, 近藤彩奈, 片山晴喜, 佐藤浩平, 畑利彰, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1532 - S1532 2022年9月

近藤宏也, 田澤大, 久禮美穂, 藤原智洋, 国定俊之, 尾崎敏文, 藤原俊義

日本癌学会総会記事 81回 J - 2087 2022年9月

悪性軟部腫瘍に対する抗CSF-1R阻害薬の有効性抗腫瘍効果と微小環境へ与える影響(Antitumor effect of CSF-1/CSF-1R blockade in soft-tissue sarcomas)

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 近藤宏也, 国定俊之, 尾崎敏文

日本癌学会総会記事 81回 J - 1062 2022年9月

浸潤型軟部肉腫におけるCathepsin Proteaseの発現の臨床病理学的意義(Clinicopathological significance of cathepsin protease expression in infiltrative soft-tissue sarcomas)

藤原智洋, Zhang Lingxin, Chandler Andrew, Yakoub Mohamed, Hameed Meera, 中田英二, 国定俊之, 尾崎敏文, Healey John

日本癌学会総会記事 81回 P - 1275 2022年9月

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 近藤宏也, 国定俊之, 尾崎敏文

日本癌学会総会記事 81回 J - 1065 2022年9月

軟部肉腫に対する抗CSF-1R阻害薬の有効性抗腫瘍効果と微小環境へ与える影響

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 近藤宏也, 片山晴喜, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1765 - S1765 2022年9月

Cathepsin proteaseは浸潤型軟部肉腫における浸潤性発育および生存予後に相関する

藤原智洋, Zhang Lingxin, Chandler Andrew, Yakoub Mohamed, 中田英二, 国定俊之, 尾崎敏文, Hameed Meera, Healey John

日本整形外科学会雑誌 96 ( 8 ) S1769 - S1769 2022年9月

MPNSTの癌幹細胞性維持に対する腫瘍内のアドレナリン合成酵素の役割

たき平将太, 山田大祐, 高尾知佳, 中田英二, 近藤宏也, 佐藤浩平, 畑利彰, 藤原智洋, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 96 ( 8 ) S1768 - S1768 2022年9月

片山晴喜, 藤村篤史, 中田英二, 大谷悠介, 藤原智洋, 国定俊之, 神谷厚範, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1768 - S1768 2022年9月

腫瘍随伴マクロファージの浸潤割合および予後を予測する血中バイオマーカーの特定浸潤性軟部肉腫患者における検討

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 近藤宏也, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 箱崎道之, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1766 - S1766 2022年9月

Effect of bacterium in the malignant wounds of soft tissue sarcoma

Eiji Nakata, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Toshiyuki Kunisada, Toshifumi Ozaki

Oncology Letters 24 ( 4 ) 2022年8月

Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study. 国際誌

Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki, Akira Kawai

BMC cancer 22 ( 1 ) 891 - 891 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade. METHODS: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017, identified from the Bone and Soft-Tissue Tumor Registry in Japan, were analyzed retrospectively. RESULTS: The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were > 25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors > 5 cm (5-10 cm, 81%; > 10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy. Overall, improved DSS for metastatic ASPS has been observed since 2012 (5-year DSS, from 58 to 65%) when pazopanib was approved for advanced diseases, although without a statistically significant difference (p = 0.117). CONCLUSION: The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted therapy encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.

DOI： 10.1186/s12885-022-09968-5

神経線維腫症1型に合併する腫瘍性病変に対するサーベイランス

モジュラー型人工関節・骨軟部腫瘍領域感染腫瘍用人工関節の術後感染

中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本骨・関節感染症学会プログラム・抄録集 45回 108 - 108 2022年7月

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本遺伝カウンセリング学会誌 43 ( 2 ) 92 - 92 2022年6月

消化器がん患者の術前がんロコモ年齢別の検討

堅山佳美, 中田英二, 千田益生, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

運動器リハビリテーション 33 ( 2 ) 136 - 136 2022年6月

人工知能による骨肉腫X線読影システムの開発と骨端線認識への挑戦

長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓昌煕, 藏品豊, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1333 - S1333 2022年6月

ゲノム医療時代の骨・軟部腫瘍医骨・軟部腫瘍診療におけるがん遺伝子パネルの意義

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1286 - S1286 2022年6月

遺伝性骨・軟部腫瘍外来の取り組み

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1315 - S1315 2022年6月

遺伝性骨・軟部腫瘍に対する遺伝学的検査の臨床的意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本整形外科学会雑誌 96 ( 6 ) S1301 - S1301 2022年6月

高悪性度非円形細胞軟部肉腫における術前化学療法の組織学的効果判定法の標準化と予後的意義 JCOG0304附随研究

遠藤誠, 小田義直, 田仲和宏, 廣瀬隆則, 長谷川匡, 蛭田啓之, 久岡正典, 国定俊之, 比留間徹, 土屋弘行, 片桐浩久, 松本嘉寛, 川井章, 中山ロバート, 川島寛之, 水澤純基, 福田治彦, 尾崎敏文, 岩本幸英, 野島孝之

日本整形外科学会雑誌 96 ( 6 ) S1423 - S1423 2022年6月

消化器がん患者の術前がんロコモ年齢別の検討

堅山佳美, 中田英二, 千田益生, 濱田全紀, 藤原智洋, 国定俊之, 尾崎敏文

運動器リハビリテーション 33 ( 2 ) 136 - 136 2022年6月

下肢悪性骨・軟部腫瘍に対する広範切除後の機能回復

濱田全紀, 中田英二, 堅山佳美, 藤原智洋, 国定俊之, 千田益生, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1433 - S1433 2022年6月

消化器がん患者の術前がんロコモ

堅山佳美, 中田英二, 千田益生, 濱田全紀, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1440 - S1440 2022年6月

ビッグデータと骨・軟部腫瘍-全国骨軟部腫瘍登録- National Cancer Databaseを利用した骨・軟部腫瘍研究社会経済的・地理的データから骨・軟部腫瘍診療の実態と課題を読み取る

藤原智洋, 小倉浩一, 中田英二, 国定俊之, 尾崎敏文, 川井章, Healey John H.

日本整形外科学会雑誌 96 ( 6 ) S1269 - S1269 2022年6月

遺伝性骨・軟部腫瘍外来の取り組み

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1315 - S1315 2022年6月

臓器指向性分泌サイトカイン/細胞外小胞を介したcell-cell communicationによる骨肉腫の新しい肺転移形成機構の同定

近藤宏也, 藤原智洋, 田澤大, 吉田晶, 片山晴喜, 近藤彩奈, 佐藤浩平, 畑利彰, たき平将太, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1424 - S1424 2022年6月

骨巨細胞腫に対するデノスマブのde-escalationの有効性

板野拓人, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1368 - S1368 2022年6月

下肢悪性骨・軟部腫瘍に対する広範切除後の機能回復

濱田全紀, 中田英二, 堅山佳美, 藤原智洋, 国定俊之, 千田益生, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1433 - S1433 2022年6月

大腿骨近位部転移性骨腫瘍に対する手術療法

佐藤浩平, 中田英二, 片山晴喜, 近藤彩奈, 近藤宏也, 畑利彰, たき平将太, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1461 - S1461 2022年6月

人工知能による骨肉腫X線読影システムの開発と骨端線認識への挑戦

長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓昌煕, 藏品豊, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1333 - S1333 2022年6月

消化器がん患者の術前がんロコモ

堅山佳美, 中田英二, 千田益生, 濱田全紀, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1440 - S1440 2022年6月

遺伝性骨・軟部腫瘍に対する遺伝学的検査の臨床的意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本整形外科学会雑誌 96 ( 6 ) S1301 - S1301 2022年6月

ゲノム医療時代の骨・軟部腫瘍医骨・軟部腫瘍診療におけるがん遺伝子パネルの意義

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1286 - S1286 2022年6月

浸潤性軟部肉腫における放射線療法の治療効果の検討

畑利彰, 藤原智洋, 吉田晶, 近藤宏也, 近藤彩奈, 片山晴喜, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1365 - S1365 2022年6月

骨盤周囲深部発生軟部肉腫の治療成績

片山晴喜, 藤原智洋, 国定俊之, 中田英二, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1363 - S1363 2022年6月

80歳以上の超高齢軟部肉腫患者の治療における老年学的因子の意義

近藤彩奈, 藤原智洋, 吉田晶, 片山晴喜, 畑利彰, 佐藤浩平, たき平将太, 近藤宏也, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1298 - S1298 2022年6月

ナビゲーション支援手術は補助療法の効果を期待しにくい骨盤軟骨肉腫の腫瘍学的予後を改善させるか

藤原智洋, 金内洋一, 津田祐輔, Stevenson Jonathan, Parry Michael, Grimer Robert, Jeys Lee, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 96 ( 6 ) S1288 - S1288 2022年6月

転移性骨腫瘍(切迫骨折の治療) 大腿骨近位部転移性骨腫瘍に対する手術療法

佐藤浩平, 依光正則, 福岡史朗, 畑利彰, 近藤宏也, 上原健敬, 中田英二, 国定俊之, 野田知之, 尾崎敏文

骨折 44 ( Suppl. ) S70 - S70 2022年6月

術前肺がん患者のサルコペニア・がんロコモと術後合併症の関連性

堅山佳美, 千田益生, 中田英二, 濱田全紀, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine ( 特別号 ) S35 - S35 2022年5月

術前肺がん患者のサルコペニア・がんロコモと術後合併症の関連性

堅山佳美, 千田益生, 中田英二, 濱田全紀, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine ( 特別号 ) S35 - S35 2022年5月

脊椎転移に対する放射線治療の有用性

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine ( 特別号 ) S621 - S621 2022年5月

骨軟部腫瘍患者の術前ストレススクリーニング

伊勢真人, 藤原智洋, 堅山佳美, 中田英二, 濱田全紀, 國定俊之, 千田益生, 尾崎敏文, 田島文博

The Japanese Journal of Rehabilitation Medicine ( 特別号 ) S629 - S629 2022年5月

A randomized phase III trial of denosumab before curettage for giant cell tumor of bone. JCOG1610

Hiroshi Urakawa, Akihito Nagano, Ryunosuke Machida, Kazuhiro Tanaka, Tomoko Kataoka, Yuta Sekino, Yoshihiro Nishida, Mitsuru Takahashi, Toshiyuki Kunisada, Masanori Kawano, Yukihiro Yoshida, Tatsuya Takagi, Kenji Sato, Toru Hiruma, Hiroshi Hatano, Satoshi Tsukushi, Akio Sakamoto, Toshihiro Akisue, Koji Hiraoka, Toshifumi Ozaki

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Though JCOG1610 gave only descriptive results, the superiority of preoperative denosumab was not observed in patients with giant cell tumor of bone without possible post-operative large bone defect in terms of relapse-free survival.Objectives The aim of JCOG1610 (randomized controlled phase III trial) was to confirm the superiority of preoperative denosumab to curettage with adjuvant local therapy for patients with giant cell tumor of bone without possible post-operative large bone defect. Methods The primary endpoint was relapse-free survival and the total sample size was set at 106 patients. Patient accrual began in October 2017. However, the accrual was terminated in December 2020 due to a recommendation from the Data and Safety Monitoring Committee because of poor patient accrual. Now, we report the descriptive results obtained in this study. Results A total of 18 patients had been registered from 13 Japanese institutions at the time of termination on December 2020. Eleven patients were assigned to Arm A (curettage and adjuvant local therapy) and 7 to Arm B (preoperative denosumab, curettage and adjuvant local therapy). Median follow-up period was 1.6 (range: 0.5-2.8) years. Protocol treatment was completed in all but one patient in Arm A who had a pathological fracture before surgery. All patients in Arm B were treated with five courses of preoperative denosumab. Relapse-free survival proportions in Arm A and B were 90.0% (95% confidence interval: 47.3-98.5) and 100% (100-100) at 1 year, and 60.0% (19.0-85.5) and 62.5% (14.2-89.3) at 2 years, respectively [hazard ratio (95% confidence interval): 1.51 (0.24-9.41)]. Conclusion In terms of relapse-free survival, the superiority of preoperative denosumab was not observed in patients with giant cell tumor of bone without possible post-operative large bone defect.

DOI： 10.1093/jjco/hyac071

骨軟部腫瘍患者におけるがん遺伝子パネル検査によるgermline findingの同定

中田英二, 藤原智洋, 国定俊之, 二川摩周, 平沢晃, 尾崎敏文

中部日本整形外科災害外科学会雑誌 65 ( 春季学会 ) 125 - 125 2022年4月

Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020 - Secondary publication.

Akira Kawai, Nobuhito Araki, Keisuke Ae, Toru Akiyama, Toshifumi Ozaki, Hirotaka Kawano, Toshiyuki Kunisada, Minako Sumi, Shunji Takahashi, Kazuhiro Tanaka, Satoshi Tsukushi, Norifumi Naka, Yoshihiro Nishida, Mitsuru Miyachi, Norio Yamamoto, Akihiko Yoshida, Tsukasa Yonemoto, Masahiro Yoshida, Shintaro Iwata

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 ( 3 ) 533 - 550 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: These clinical practice guidelines are intended to provide recommendations based on the best evidence obtained to date on key issues in clinical practice to improve the prognosis, diagnostic and therapeutic processes for patients with soft tissue tumors. METHODS: The Guidelines Development Committee and Systematic Review Committee were composed of a multidisciplinary team of specialists who play an important role in soft tissue tumor care. Clinical questions (CQs) were determined by choosing key decision-making points based on Algorithms for the diagnosis and treatment of soft tissue tumors. The guidelines were developed according to the "Medical Information Network Distribution Service (Minds) Handbook for Clinical Practice Guideline Development 2014" and "Minds Manual for Clinical Practice Guideline Development 2017." Recommendation strength was rated on two levels and the strength of evidence was rated on four levels. The recommendations were decided based on agreement by 70% or more voters. RESULTS: Twenty-two CQs were chosen by the Guidelines Development Committee. The Systematic Review Committee reviewed the evidence concerning each CQ, a clinical value judgment was added by experts, and the text of each recommendation was determined. CONCLUSION: We established 22 CQs and recommendations for key decision-making points in the diagnosis and treatment of soft tissue tumors according to the Minds Clinical Practice Guideline development methods. We hope that these guidelines will assist the decision-making of all medical staff engaged in the treatment and diagnosis of soft tissue tumors, and eventually lead to improved soft tissue tumor care in the country.

DOI： 10.1016/j.jos.2021.11.023

がんゲノム中核拠点病院における、がん遺伝子パネルで同定されたGermline Findingsに対する診療システムの構築

中田英二, 二川摩周, 国定俊之, 藤原智洋, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S439 - S439 2022年3月

肉腫におけるがん遺伝子パネルの有用性

中田英二, 国定俊之, 藤原智洋, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 3 ) S626 - S626 2022年3月

骨・軟部腫瘍診療の未来骨・軟部腫瘍診療におけるAI診断の現状と未来

長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓昌煕, 藏品豊, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S479 - S479 2022年3月

60歳以上の術前がん患者のがんロコモとサルコペニアの有病率

堅山佳美, 中田英二, 藤原智洋, 国定俊之, 濱田全紀, 千田益生, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S120 - S120 2022年3月

骨・軟部腫瘍診療の未来骨・軟部腫瘍診療におけるAI診断の現状と未来

長谷井嬢, 中原龍一, 国定俊之, 中澤慎二, 韓昌煕, 藏品豊, 木浪陽, 藤原一夫, 臼井正明, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S479 - S479 2022年3月

がんゲノム中核拠点病院における、がん遺伝子パネルで同定されたGermline Findingsに対する診療システムの構築

中田英二, 二川摩周, 国定俊之, 藤原智洋, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 2 ) S439 - S439 2022年3月

本邦の胞巣状軟部肉腫に対する治療実態とその成績全国骨・軟部腫瘍登録を用いた研究

藤原智洋, 中田英二, 国定俊之, 尾崎敏文, 川井章

日本整形外科学会雑誌 96 ( 3 ) S1156 - S1156 2022年3月

肉腫におけるがん遺伝子パネルの有用性

中田英二, 国定俊之, 藤原智洋, 二川摩周, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 3 ) S626 - S626 2022年3月

骨腫瘍切除後の配向連通孔構造を持つβ-TCPによる再建

近藤彩奈, 中田英二, 国定俊之, 藤原智洋, たき平将太, 近藤宏也, 佐藤浩平, 畑利彰, 片山晴喜, 尾崎敏文

移植 56 ( 4 ) 456 - 456 2022年2月

Soft-tissue sarcoma in adolescents and young adults 査読

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Ako Hosono, Shota Takihira, Hiroya Kondo, Toshifumi Ozaki

International Journal of Clinical Oncology 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Soft-tissue sarcoma is a rare cancer that accounts for approximately 1% of all malignant tumors. Although they occur in various age groups, soft-tissue sarcomas account for 8% of all malignant tumors developing in adolescents and young adults, suggesting that they are not rare in this age group. This study aimed to evaluate the clinical and pathological characteristics of soft-tissue sarcoma in adolescents and young adults. According to the Bone and Soft-Tissue Tumor Registry in Japan, myxoid liposarcoma is the most common type of soft-tissue sarcoma found in adolescents and young adults; alveolar soft part sarcoma, extraskeletal Ewing sarcoma, epithelioid sarcoma, clear cell sarcoma and synovial sarcoma occur predominantly in this age group among soft-tissue sarcomas. The analysis based on this registry demonstrated that age was not a prognostic factor for poor survival of soft-tissue sarcoma, although the prognosis in adolescents and young adults was better than that in older patients in the US and Scandinavia. Adolescent and young adult patients with soft-tissue sarcoma have age-specific problems, and a multidisciplinary approach to physical, psychological, and social issues is necessary to improve the management of these young patients both during and after treatment.

DOI： 10.1007/s10147-022-02119-7

What are the Results of Resection of Forearm Soft Tissue Sarcoma?

その他リンク： https://link.springer.com/article/10.1007/s10147-022-02119-7/fulltext.html

Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Ryuichi Nakahara, Toshiyuki Watanabe, Toshifumi Ozaki

2021年11月

出版者・発行元：Research Square Platform LLC

Abstract

Only few reports have assessed the characteristics and oncological and functional outcomes of forearm soft tissue sarcomas (STS). Then, we aimed to investigate the clinical features and survival-related factors for forearm STS who underwent surgical excision at our institution. There were 38 patients. Fourteen patients (41%) were referred to our institution after an unplanned excision and tumor size and grade were significantly associated with the receipt of it. The postoperative median Musculoskeletal Tumor Society rating scale (MSTS) score was 28. Bone resection or major nerve palsy was the only factor influencing the postoperative MSTS score (P < 0.001). There was no significant difference in MSTS scores according to the reconstruction procedures (the use of flap or tendon reconstruction). The 5-year local recurrence-free survival (LRFS) rate was 86%. Univariate analysis revealed that the histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS (P = 0.047). The 5-year metastasis-free survival rate was 77%. The 5-year overall survival (OS) rate was 94%. Age was the only factor that influenced OS (P = 0.01). In conclusion, reconstruction of the skin and tendon can compensate for function. Careful follow-up is important, especially in patients with myxofibrosarcoma, due to its likelihood of local recurrence.

DOI： 10.21203/rs.3.rs-1028963/v1

【脊椎転移の治療最前線】脊椎転移に対する放射線治療の有用性

その他リンク： https://www.researchsquare.com/article/rs-1028963/v1.html

良性腫瘍に対する低侵襲治療類骨骨種に対するRFA

冨田晃司, 馬越紀行, 宇賀麻由, 藤原智洋, 松井裕輔, 中田英二, 生口俊浩, 国定俊之, 平木隆夫, 尾崎敏文

日本小児整形外科学会雑誌 30 ( 3 ) S39 - S39 2021年11月

良性腫瘍に対する低侵襲治療術中CTナビゲーションを用いた類骨骨腫に対する低侵襲手術

藤原智洋, 国定俊之, 中田英二, 尾崎敏文

日本小児整形外科学会雑誌 30 ( 3 ) S38 - S38 2021年11月

中田英二, 国定俊之, 藤原智洋, 杉原進介, 明崎禎輝, 金重総一郎, 尾崎敏文

臨床整形外科 56 ( 10 ) 1249 - 1256 2021年10月

記述言語：日本語出版者・発行元：(株)医学書院

＜文献概要＞脊椎転移による痛みに対しては,麻痺がない場合は放射線治療(RT)単独で早期に除痛が得られ,経時的に骨形成を認める場合が多い.標準的なRTは前後対向2門照射を用いた通常照射(分割照射:30Gy/10回)であるが,予後不良(3〜6ヵ月以内)であれば8Gy単回照射で十分である.麻痺を認める場合は除圧術とRTの併用を検討すべきである.最近,体幹部定位放射線治療の有用性が報告されているが,治療計画に時間を要するなどの欠点がある.なお,脊椎転移を有する患者に背部痛が出現した場合,脊椎転移による麻痺リスクを考慮し,早急に画像検査を行うべきである(red flag).

【脊椎転移の治療最前線】脊椎転移に対する放射線治療の有用性

中田英二, 国定俊之, 藤原智洋, 杉原進介, 明崎禎輝, 金重総一郎, 尾崎敏文

臨床整形外科 56 ( 10 ) 1249 - 1256 2021年10月

記述言語：日本語出版者・発行元：(株)医学書院

術前がん患者におけるがんロコモ・サルコペニアの有病率

堅山佳美, 中田英二, 濱田全紀, 国定俊之, 藤原智洋, 千田益生, 尾崎敏文

中国・四国整形外科学会雑誌 33 ( 3 ) 324 - 324 2021年10月

Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. 査読国際誌

Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Yusuke Mochizuki, Hiroya Kondo, Shuhei Osaki, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Koji Ueda, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Cancer chemotherapy and pharmacology 88 ( 3 ) 513 - 524 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.

DOI： 10.1007/s00280-021-04310-5

骨肉腫における腫瘍関連マクロファージの役割とin vitro実験による検証

肉腫におけるがん遺伝子パネルによる融合遺伝子の検出

中田英二, 国定俊之, 藤原智洋, 遠西大輔, 冨田秀太, 尾崎敏文

中部日本整形外科災害外科学会雑誌 64 ( 秋季学会 ) 107 - 107 2021年9月

肺転移能を有する骨肉腫細胞はM2様マクロファージへの分化を強力に誘導する

近藤宏也, 田澤大, 久禮美穂, 藤原智洋, 国定俊之, 尾崎敏文, 藤原俊義

日本癌学会総会記事 80回 [J14 - 4] 2021年9月

がん患者における周術期のがんロコモの発生率とそのリスクファクター

堅山佳美, 中田英二, 明崎禎輝, 千田益生, 国定俊之, 濱田全紀, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1580 - S1580 2021年8月

肉腫におけるがんゲノム医療の意義

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1549 - S1549 2021年8月

近藤宏也, 田澤大, 久禮美穂, 藤原智洋, 佐藤浩平, 畑利彰, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1556 - S1556 2021年8月

Pexidartinibの骨肉腫に対する前臨床的検討 CSF-1/CSF-1R阻害は肉腫微小環境の免疫細胞構成分画を変化させ抗腫瘍効果を発揮する

たき平将太, 山田大祐, 高尾知佳, 中田英二, 近藤宏也, 佐藤浩平, 畑利彰, 藤原智洋, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 95 ( 8 ) S1554 - S1554 2021年8月

藤原智洋, Yakoub Mohamed, 吉田晶, 近藤宏也, 畑利彰, 佐藤浩平, たき平将太, 中田英二, 国定俊之, 尾崎敏文, Healey John

日本整形外科学会雑誌 95 ( 8 ) S1557 - S1557 2021年8月

畑利彰, 藤原智洋, 吉田晶, 近藤彩奈, 片山晴喜, 佐藤浩平, 近藤宏也, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1552 - S1552 2021年8月

がん患者における周術期のがんロコモの発生率とそのリスクファクター

堅山佳美, 中田英二, 明崎禎輝, 千田益生, 国定俊之, 濱田全紀, 尾崎敏文

日本整形外科学会雑誌 95 ( 8 ) S1580 - S1580 2021年8月

がんロコモの現状と課題遠隔転移のないがん患者における周術期のがんロコモの発生率とそのリスクファクター

堅山佳美, 中田英二, 明崎禎輝, 千田益生, 国定俊之, 濱田全紀, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1298 - S1298 2021年6月

がんロコモの現状と課題がんロコモ発生予防のための院内システムの構築

中田英二, 堅山佳美, 明崎禎輝, 濱田全紀, 国定俊之, 藤原智洋, 千田益生, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1241 - S1241 2021年6月

骨・軟部腫瘍のgermline findingsに対する遺伝子医療部門の取り組み

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1251 - S1251 2021年6月

肉腫における免疫療法

たき平将太, 佐藤浩平, 畑利彰, 近藤宏也, 中田英二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1338 - S1338 2021年6月

NICE軟部肉腫ガイドラインは英国における軟部肉腫患者の診療体制や生存予後にどのような影響を与えたか

藤原智洋, Grimer Robert, Evans Scott, 津田祐輔, 中田英二, 国定俊之, 尾崎敏文, Abudu Adesegun

日本整形外科学会雑誌 95 ( 6 ) S1371 - S1371 2021年6月

前腕に発生した肉腫の治療成績

畑利彰, 佐藤浩平, 近藤宏也, たき平将太, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1354 - S1354 2021年6月

骨肉腫における腫瘍関連マクロファージの臨床病理学的意義

近藤宏也, 藤原智洋, 吉田晶, 佐藤浩平, 畑利彰, たき平将太, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1410 - S1410 2021年6月

肉腫の心臓転移

板野拓人, 中田英二, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1389 - S1389 2021年6月

がんゲノム中核拠点病院における肉腫のがんゲノム医療

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1252 - S1252 2021年6月

寛骨臼を含む骨盤発生Ewing肉腫に対する英国集約化施設における治療変遷とその成績

藤原智洋, Stevenson Jonathan, Parry Michael, 津田祐輔, 中田英二, 国定俊之, 尾崎敏文, Grimer Robert, Jeys Lee

日本整形外科学会雑誌 95 ( 6 ) S1272 - S1272 2021年6月

がん遺伝子パネルによる肉腫における融合遺伝子の検出

佐藤浩平, 中田英二, 近藤宏也, 畑利彰, たき平将太, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 95 ( 6 ) S1269 - S1269 2021年6月

Prevalence of Psychological Distress and Its Risk Factors in Patients with Primary Bone and Soft Tissue Tumors. 査読国際誌

Masato Ise, Eiji Nakata, Yoshimi Katayama, Masanori Hamada, Toshiyuki Kunisada, Tomohiro Fujiwara, Ryuichi Nakahara, Shouta Takihira, Kohei Sato, Yoshiteru Akezaki, Masuo Senda, Toshifumi Ozaki

Healthcare (Basel, Switzerland) 9 ( 5 ) 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Psychological distress is common in patients with soft tissue and bone tumors. We first investigated its frequency and the associated risk factors in patients with pre-operative bone and soft tissue tumors. Participants included 298 patients with bone and soft tissue tumors who underwent surgery in our institution between 2015 and 2020. Psychological distress was evaluated by the Distress and Impact Thermometer (DIT) that consists of two types of questions (questions about the severity of the patient's distress (DIT-D) and its impact (DIT-I)). We used a cut-off point of 4 on the DIT-D and 3 on the DIT-I for screening patients with psychological distress. We therefore investigated: (1) the prevalence of psychological distress as assessed with DIT or distress thermometer (DT), which can be decided by DIT-D ≥ 4, (2) what are the risk factors for the prevalence of psychological distress, and (3) what is the number of patients who consulted a psychiatrist for psychological distress in patients with pre-operative bone and soft tissue tumors. With DIT and DT, we identified 64 patients (21%) and 95 patients (32%), respectively, with psychological distress. Multivariate logistic regression revealed that older age, sex (female), malignancy (malignant or intermediate tumor), a lower Barthel Index, and higher numeric rating scale were risk factors for psychological distress. Two patients (3%) consulted a psychiatrist after surgery. In conclusion, careful attention to psychological distress is needed, especially for female patients, older patients, and those with malignant soft or bone tissue tumors who have more than moderate pain.

DOI： 10.3390/healthcare9050566

脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021年5月

Telomerase-specific oncolytic immunotherapy for promoting efficacy of PD-1 blockade in osteosarcoma. 査読国際誌

Yusuke Mochizuki, Hiroshi Tazawa, Koji Demiya, Miho Kure, Hiroya Kondo, Tadashi Komatsubara, Kazuhisa Sugiu, Joe Hasei, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Cancer immunology, immunotherapy : CII 70 ( 5 ) 1405 - 1417 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1) antibody have recently improved clinical outcome in certain cancer patients; however, osteosarcoma (OS) patients are refractory to PD-1 blockade. Oncolytic virotherapy has emerged as novel immunogenic therapy to augment antitumor immune response. We developed a telomerase-specific replication-competent oncolytic adenovirus OBP-502 that induces lytic cell death via binding to integrins. In this study, we assessed the combined effect of PD-1 blockade and OBP-502 in OS cells. The expression of coxsackie and adenovirus receptor (CAR), integrins αvβ3 and αvβ5, and programmed cell death ligand 1 (PD-L1) was analyzed in two murine OS cells (K7M2, NHOS). The cytopathic activity of OBP-502 in both cells was analyzed using the XTT assay. OBP-502-induced immunogenic cell death was assessed by analyzing the level of extracellular ATP and high-mobility group box protein B1 (HMGB1). Subcutaneous tumor models for K7M2 and NHOS cells were used to evaluate the antitumor effect and number of tumor-infiltrating CD8+ cells in combination therapy. K7M2 and NHOS cells showed high expression of integrins αvβ3 and αvβ5, but not CAR. OBP-502 significantly suppressed the viability of both cells, in which PD-L1 expression and the release of ATP and HMGB1 were significantly increased. Intratumoral injection of OBP-502 significantly augmented the efficacy of PD-1 blockade on subcutaneous K2M2 and NHOS tumor models via enhancement of tumor-infiltrating CD8+ T cells. Our results suggest that telomerase-specific oncolytic virotherapy is a promising antitumor strategy to promote the efficacy of PD-1 blockade in OS.

DOI： 10.1007/s00262-020-02774-7

脊椎転移に対する集学的治療麻痺を認めない脊椎SREに対する保存的治療の成績

中田英二, 国定俊之, 藤原智洋, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine 58 ( 特別号 ) JSY39 - 1 2021年5月

Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. 査読国際誌

Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Shintaro Iwata, Tsukasa Yonemoto, Koji Ueda, Toshifumi Ozaki

Cancers 13 ( 8 ) 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

DOI： 10.3390/cancers13081823

Immunotherapy for sarcomas. 査読国際誌

Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Tastuo Ito, Shota Takihira, Toshifumi Ozaki

Japanese journal of clinical oncology 51 ( 4 ) 523 - 537 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte-associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.

DOI： 10.1093/jjco/hyab005

【骨・軟部腫瘍のマネジメント(その1)】総論診療体制サルコーマセンター設立と腫瘍内科医との連携集約化と地域連携

国定俊之, 中田英二, 藤原智洋, 久保寿夫, 西森久和, 田端雅弘, 尾崎敏文

別冊整形外科 ( 79 ) 7 - 12 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめにわが国では歴史的に整形外科が中心となって肉腫(サルコーマ)の治療方針を決め,主に手術と化学療法を担当してきた.一方,欧米では腫瘍内科が肉腫の化学療法を担当することが一般的であり,わが国の治療状況とは大きく異なる.肉腫治療例の増加とともに進行例が増加し,新規治療薬も開発され,整形外科医のみで治療していくことがむずかしくなってきた.また,化学療法以外にも,肉腫の診断,手術には多くの診療科の協力が必要で,多職種による集学的医療チームによる治療が重要である.当院では肉腫患者によりよい治療を提供する目的で,2014年4月に大学病院の診療部門としては日本ではじめてサルコーマセンターを設立した.本稿では,当院サルコーマセンターの活動を紹介する.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600002&doc_link_id=10.15106%2Fj_besei79_7&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_7&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【骨・軟部腫瘍のマネジメント(その1)】診断組織・遺伝子診断骨・軟部腫瘍におけるリキッドバイオプシーの開発

藤原智洋, 中田英二, 国定俊之, 尾崎敏文

別冊整形外科 ( 79 ) 63 - 69 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめに-リキッドバイオプシーとはリキッドバイオプシーとは,血液,尿,唾液などの体液中に含まれる細胞,核酸,蛋白質,代謝物などの生体分子の解析から病態の把握をめざす病態診断技術の総称である.この用語は,2010年代に血液中に存在する循環腫瘍細胞(circulating tumor cells:CTC)の検出による診断法に与えられたものであり,その後,核酸,蛋白質,代謝物などのさまざまな生体分子を対象とした解析法に対しても用いられるようになっている.現在では,循環腫瘍DNA(circulating tumor DNA:ctDNA),疾患特異的なマイクロRNA(microRNA:miRNA)などの核酸分子や,癌細胞由来のエクソソームの検出による疾患診断法の開発が精力的にすすめられている(図1).リキッドバイオプシーは非侵襲的かつ簡便に施行することができ,同一症例に対して繰り返し施行することが可能であるため,診断だけでなく治療効果や予後の予測に有用であり,次世代の診断技術の基盤として期待が集まっている.骨・軟部腫瘍には,消化器癌,前立腺癌,婦人科癌などの存在診断,治療効果予測,再発リスクの予測,術後再発のモニタリングなどに用いられる血液腫瘍マーカーがきわめて少ない.2012年の『軟部腫瘍診療ガイドライン』では,「臨床検査値で異常を示す腫瘍は?」というクリニカルクエスチョンに対して「軟部腫瘍で特異的な腫瘍マーカーは一般的にはない」と記載されている.癌腫と同様に乳酸脱水素酵素(LDH)の上昇を認めることがあるが,一般的には腫瘍サイズの大きな高悪性度軟部肉腫,あるいは多発性に転移して進行した軟部肉腫に限られる.このような背景から,肉腫細胞由来の生体分子を用いたリキッドバイオプシーの開発は,骨・軟部腫瘍の診療における新しいブレイクスルーとなる可能性があり,研究開発が精力的に行われている.本稿では,リキッドバイオプシーの骨・軟部腫瘍における研究開発の動向を生体分子別に述べ,本法の将来展望について論じる.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600014&doc_link_id=10.15106%2Fj_besei79_63&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_63&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【骨・軟部腫瘍のマネジメント(その1)】治療総論免疫療法肉腫における免疫療法

中田英二, 藤原智洋, たき平将太, 国定俊之, 尾崎敏文

別冊整形外科 ( 79 ) 149 - 157 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめに肉腫における免疫療法の歴史は古く,1891年,William Coley博士は切除不能で転移性の肉腫の患者において免疫療法の効果を最初に示した.その後,免疫調節薬,ワクチンなどさまざまな免疫療法が開発され,最近は免疫チェックポイント阻害薬(immune-check point inhibitor:ICI)や活性化自己リンパ球輸注療法などの有望な治療法が登場している(表1).本稿では肉腫の免疫療法についてレビューを行う.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600029&doc_link_id=10.15106%2Fj_besei79_149&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_149&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

【骨・軟部腫瘍のマネジメント(その1)】診断組織・遺伝子診断肉腫におけるがんゲノム医療の意義

中田英二, 藤原智洋, 国定俊之, 尾崎敏文, 遠西大輔, 冨田秀太, 平沢晃, 二川摩周, 武田達明

別冊整形外科 ( 79 ) 75 - 83 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめにがんにはさまざまな遺伝子異常を認め,同一のがん種でも発現する遺伝子が異なることが少なくない.最近,次世代シークエンサー(next generation sequencer:NGS)を用いて遺伝子異常を同時多重性(マルチプレックス)に検出するがん遺伝子パネルが登場した.がんゲノム医療では,がん遺伝子パネルで同定した遺伝子変異に基づいて薬剤を選択する,精密医療(precision medicine)が行われる.本稿では,肉腫におけるゲノム医療の意義について述べる.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600016&doc_link_id=10.15106%2Fj_besei79_75&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_75&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Role of Tumor-Associated Macrophages in Sarcomas. 査読国際誌

Tomohiro Fujiwara, John Healey, Koichi Ogura, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Miho Kure, Hiroshi Tazawa, Eiji Nakata, Toshiyuki Kunisada, Toshiyoshi Fujiwara, Toshifumi Ozaki

Cancers 13 ( 5 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

DOI： 10.3390/cancers13051086

【希少がん-がん診療の新たな課題-】希少がん疾患各論骨軟部腫瘍・肉腫骨肉腫

国定俊之, 中田英二, 藤原智洋, 尾崎敏文

日本臨床 79 ( 増刊1 希少がん ) 454 - 461 2021年3月

(IV章)骨軟部骨腫瘍原発性悪性骨腫瘍の治療指針

国定俊之, 中田英二, 尾崎敏文

整形外科学レビュー 2021-'22 228 - 232 2021年3月

The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas. 査読

Hiromasa Yamamoto, Kei Namba, Haruchika Yamamoto, Tomohiro Toji, Junichi Soh, Kazuhiko Shien, Ken Suzawa, Takeshi Kurosaki, Shinji Otani, Mikio Okazaki, Seiichiro Sugimoto, Masaomi Yamane, Katsuhito Takahashi, Toshiyuki Kunisada, Takahiro Oto, Shinichi Toyooka

Surgery today 51 ( 1 ) 127 - 135 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Sarcomas are among the most refractory malignant tumors and often recur as pulmonary metastasis. Although the presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with the prognosis of several malignancies, the relationship between the NLR and sarcoma with pulmonary metastasis is unclear. We investigated the impact of the NLR in patients who underwent surgical resection for metastatic lung tumors from various sarcomas. METHODS: The subjects of this retrospective study were 158 patients with metastatic lung tumors from various sarcomas, who underwent initial pulmonary metastasectomy between 2006 and 2015. We examined the clinicopathological variables, including the NLR and the characteristics of surgical procedures. Survival was estimated by the Kaplan-Meier method and prognostic factors were evaluated by multivariate analysis. RESULTS: Multivariate analysis revealed significantly better survival of the group with an NLR < 2.26 immediately before the most recent pulmonary metastasectomy, in addition to such factors as the largest resected lesion being < 22 mm, a disease-free interval of > 2 years, and 3 or more pulmonary metastasectomies. CONCLUSION: The NLR immediately before the most recent pulmonary metastasectomy is a novel independent prognostic factor, which may be helpful when considering repeated pulmonary metastasectomy.

DOI： 10.1007/s00595-020-02093-5

PRRX1 promotes malignant properties in human osteosarcoma. 査読国際誌

Ryoji Joko, Daisuke Yamada, Masahiro Nakamura, Aki Yoshida, Shota Takihira, Tomoka Takao, Ming Lu, Kohei Sato, Tatsuo Ito, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada

Translational oncology 14 ( 1 ) 100960 - 100960 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.

DOI： 10.1016/j.tranon.2020.100960

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression. 査読国際誌

Toshinori Omori, Hiroshi Tazawa, Yasuaki Yamakawa, Shuhei Osaki, Joe Hasei, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

PloS one 16 ( 4 ) e0250643 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

DOI： 10.1371/journal.pone.0250643

Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. 査読国際誌

Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 21578 - 21578 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities? 査読

Eiji Nakata, Toshiyuki Kunisada, Joe Hasei, Ryuichi Nakahara, Hiroyuki Yanai, Tomohiro Toji, Hirofumi Inoue CT, Toshifumi Ozaki

Clinical Orthopaedics & Related Research 478 ( 11 ) 2550 - 2561 2020年11月

軟部肉腫に対するトラベクテジン投与時の腫瘍反応および有害事象発現の時間経過分析

遠藤誠, 高橋俊二, 荒木信人, 杉浦英志, 上田孝文, 米本司, 高橋満, 森岡秀夫, 平賀博明, 比留間徹, 国定俊之, 松峯昭彦, 合田風人, 川井章

日本癌治療学会学術集会抄録集 58回 O39 - 1 2020年10月

【肉腫-基礎・臨床の最新知見-】肉腫の外科的治療その他術後リハビリテーション

杉原進介, 国定俊之, 尾崎敏文

日本臨床 78 ( 増刊5 肉腫 ) 415 - 419 2020年10月

【肉腫-基礎・臨床の最新知見-】肉腫の外科的治療切除ナビゲーションサージェリー

国定俊之, 中田英二, 長谷井嬢, 尾崎敏文

日本臨床 78 ( 増刊5 肉腫 ) 315 - 320 2020年10月

Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. 査読国際誌

Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Toshiyuki Kozuki, Daijiro Harada, Naoyuki Nogami, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Toshifumi Ozaki

Oncology letters 20 ( 3 ) 2977 - 2986 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

DOI： 10.3892/ol.2020.11856

Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study. 査読国際誌

Hiroshi Urakawa, Akira Kawai, Takahiro Goto, Hiroaki Hiraga, Toshifumi Ozaki, Hiroyuki Tsuchiya, Robert Nakayama, Norifumi Naka, Yoshihiro Matsumoto, Eisuke Kobayashi, Tomotake Okuma, Toshiyuki Kunisada, Masahiko Ando, Takafumi Ueda, Yoshihiro Nishida

Cancer science 111 ( 9 ) 3303 - 3312 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Alveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single-arm, multicenter, investigator-initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end-point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow-up period was 22.2 (range, 4.9-24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors.

DOI： 10.1111/cas.14542

Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan. 査読国際誌

Yoshihiro Nishida, Shunsuke Hamada, Akira Kawai, Toshiyuki Kunisada, Akira Ogose, Yoshihiro Matsumoto, Keisuke Ae, Junya Toguchida, Toshifumi Ozaki, Akihiro Hirakawa, Toru Motoi, Tomohisa Sakai, Eisuke Kobayashi, Tabu Gokita, Takeshi Okamoto, Tomoya Matsunobu, Koki Shimizu, Hiroshi Koike

Cancer science 111 ( 8 ) 2935 - 2942 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

DOI： 10.1111/cas.14528

【がんロコモ:がん診療のニューフロンティア】(Part7)オートメーションのニューフロンティア(がんロコモ診療のオートメーション化) 脊椎転移による麻痺の予防レッドフラッグ

中田英二, 国定俊之, 杉原進介, 尾崎敏文

Bone Joint Nerve 10 ( 3 ) 447 - 457 2020年7月

Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. 査読国際誌

Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 9414 - 9414 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

DOI： 10.1038/s41598-020-66120-8

Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials. 国際誌

Makoto Endo, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Kazato Goda, Akira Kawai

Cancer medicine 9 ( 11 ) 3656 - 3667 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The time course of the response to each drug is important to avoid inappropriate termination of treatment by misjudging tumor progression; however, little is known about soft tissue sarcoma (STS) regarding this matter. This study aimed to perform a time-lapse analysis of tumor response in patients with STS treated with trabectedin from 2 phase II clinical trials. We examined 66 patients with translocation-related sarcoma registered in 2 Japanese phase II clinical trials. All patients previously received standard therapy before the administration of trabectedin at 1.2 mg/m2 every 3 weeks. Imaging evaluation was performed according to the study protocol. The sum of the maximum diameters of the target lesions was calculated and analyzed over time. Among the 66 patients, 9 (13.6%) showed partial response (PR) to trabectedin. Histological diagnoses of these 9 responders comprised 6 myxoid liposarcoma, 2 synovial sarcoma, and a mesenchymal chondrosarcoma. The median period from treatment initiation to the first PR was 123 (range, 34-328) days. The pattern of tumor response to trabectedin showed an increasing tendency in size in the initial stage, usually followed by a size decrease with repeated administration. STS response to trabectedin was characterized as delayed and potentially persistent. Clinicians treating STS with trabectedin should know the features of the response pattern to avoid interrupting the treatment before maximal efficacy is achieved.

DOI： 10.1002/cam4.2991

整形トピックス骨肉腫に対する抗PD-1抗体の効果増強をめざした腫瘍融解ウイルス併用複合免疫療法の開発

望月雄介, 田澤大, 出宮光二, 久禮美穂, 長谷井嬢, 中田英二, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

整形外科 71 ( 7 ) 786 - 786 2020年6月

Definitive radiation therapy in patients with unresectable desmoid tumors: a systematic review. 査読国際誌

Tomoya Matsunobu, Toshiyuki Kunisada, Toshifumi Ozaki, Yukihide Iwamoto, Masahiro Yoshida, Yoshihiro Nishida

Japanese journal of clinical oncology 50 ( 5 ) 568 - 573 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Desmoid tumors are rare soft tissue tumors. Wide local excision has been the standard surgical treatment for desmoid tumors. However, this procedure results in high local recurrence rates, so non-surgical treatments should be considered. The aim of this systematic review was to evaluate the effect of radiation therapy on patients with desmoid tumors, especially those with unresectable disease. METHODS: We evaluated studies published between 1 January 1990 and 31 August 2017 and cited in PubMed and Ichushi (in Japanese). All studies evaluating the effect of radiation therapy on desmoid tumors were included. Data regarding radiation dose, recurrence and adverse events were recorded. RESULTS: Among 218 identified studies, only 6 were finally included in this review. Local control was achieved in 253 of 317 patients with unresectable or unresected tumors who underwent definitive radiation therapy (the crude rate of local control was 79.8%). Toxicity was evaluated in patients who underwent definitive radiation therapy or surgery plus radiation therapy. One of the most common acute complications was skin toxicity. Frequent late complications of radiation therapy included fibrosis/contracture/joint stiffness, skin disorders, lymphedema and pain. Six patients developed secondary malignancies in the radiation field. CONCLUSIONS: In patients treated unsuccessfully with surgery, watchful waiting and pharmacotherapy, radiation therapy may be an option as salvage therapy because of the high rate of local control. Because desmoid tumors frequently develop in young individuals, children and young patients who receive radiation therapy for the treatment of desmoid tumors should be followed up on a long-term basis with periodic monitoring for late radiation toxicities.

DOI： 10.1093/jjco/hyaa007

Multidisciplinary treatment system for bone metastases for early diagnosis, treatment and prevention of malignant spinal cord compression. 査読国際誌

Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Kazuo Nakanishi, Yoshiteru Akezaki, Toshifumi Ozaki

Oncology letters 19 ( 4 ) 3137 - 3144 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Malignant spinal cord compression (MSCC) is a serious complication of cancers. The present study aimed to establish a multidisciplinary treatment system for urgent magnetic resonance imaging (MRI) and referral to orthopedists in order to prevent neurological deficits caused by MSCC. In the present study, the extent to which this system achieved early diagnosis and treatment and prevented MSCC-caused neurological deficits was examined. The records from patients with neurological deficits caused by MSCC before (between April 2007 and March 2012; group A) and after (between April 2012 and March 2017; group B) the establishment of the multidisciplinary system at the Shikoku Cancer Center (Ehime, Japan) were retrospectively evaluated. The numbers of patients with neurological deficits were 38 and 7 in groups A and B, respectively. All patients received radiotherapy. The incidence of neurological deficits was 13.2 and 3.4% in groups A and B, respectively (P<0.001). The proportion of patients with improvement in the severity of neurological deficits was 5.3 and 28.6% in groups A and B, respectively (P<0.001). The interval between physicians' recognition of a neurological deficit and MRI and the start of treatment, the number of cases, and the severity of neurological deficits were evaluated in groups A and B. The median interval between recognition of a neurological deficit by physicians and MRI was 3 and 0 days in groups A and B, respectively (P<0.001). The median interval between physicians' recognition of a neurological deficit and the start of treatment was 3 and 0 days in groups A and B, respectively (P<0.001). By using a multidisciplinary treatment system, the incidence and severity of neurological deficits following treatment were significantly improved. Therefore, the multidisciplinary treatment system used in the present study may be useful for early diagnosis, treatment and prevention of MSCC in patients with bone metastases.

DOI： 10.3892/ol.2020.11415

Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients 査読

Akihito Nagano, Seiichi Matsumoto, Akira Kawai, Tomotake Okuma, Hiroaki Hiraga, Yoshihiro Matsumoto, Yoshihiro Nishida, Tsukasa Yonemoto, Masami Hosaka, Mitsuru Takahashi, Hideki Yoshikawa, Toshiyuki Kunisada, Kunihiro Asanuma, Norifumi Naka, Makoto Emori, Tadahiko Kubo, Hiroyuki Kawashima, Teruya Kawamoto, Ryohei Yokoyama, Satoshi Tsukushi, Kenji Sato, Takeshi Okamoto, Koji Hiraoka, Hideo Morioka, Kazuhiro Tanaka, Tatsuya Takagi, Yukihide Iwamoto, Toshifumi Ozaki

Journal of Orthopaedic Science 25 ( 2 ) 319 - 323 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

© 2019 The Japanese Orthopaedic Association Background: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. Methods: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. Results: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. Conclusions: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

DOI： 10.1016/j.jos.2019.04.008

Molecular radiosensitization of soft tissue sarcoma by oncolytic virus-mediated MCL1 ablation

骨肉腫X線画像の読影を目指した人工知能の開発

長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本CAOS研究会・日本最小侵襲整形外科学会プログラム・抄録集 14回・26回 135 - 135 2020年3月

Omori T, Tazawa H, Yamakawa Y, Osaki S, Hasei J, Sugiu K, Komatsubara T, Fujiwara T, Yoshida A, Kunisada T, Urata Y, Kagawa S, Ozaki T, Fujiwara T

2020年1月

Standard Treatment Remains the Recommended Approach for Patients with Bone Sarcoma Who Underwent Unplanned Surgery: Report from the Japanese Musculoskeletal Oncology Group. 査読国際誌

Tomoki Nakamura, Jun Sugaya, Norifumi Naka, Hiroshi Kobayashi, Tomotake Okuma, Toshiyuki Kunisada, Kunihiro Asanuma, Hedetatsu Outani, Shunji Nishimura, Hiroyuki Kawashima, Toru Akiyama, Taketoshi Yasuda, Shinji Miwa, Akihiro Sudo, Takafumi Ueda

Cancer management and research 12 10017 - 10022 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: The outcomes of unplanned surgery for bone sarcomas have not been frequently discussed. However, it is important to recognize patterns, treatment, and clinical outcomes of unplanned surgeries for patients with bone sarcomas. This multicenter study aimed to characterize the clinical outcomes of patients with bone sarcomas who underwent unplanned surgeries. Patients and Methods: Data of 43 patients with bone sarcomas who underwent unplanned surgery between 2006 and 2017 were obtained from 23 hospitals in Japan. These included 18 cases of osteosarcoma, 9 of Ewing sarcoma, 8 of chondrosarcoma, and 6 of undifferentiated pleomorphic sarcoma. The study included 28 men and 15 women, with a mean age of 46 years. The mean follow-up duration was 59 months. Results: The main primary tumor sites were the femur (n = 19), spine (n = 6), pelvis (n = 5), tibia (n = 3), and humerus (n = 3). The primary diagnoses were benign bone tumor (n = 24), trauma (n = 7), bone metastasis (n = 5), osteomyelitis (n = 4), degeneration (n=2), and unknown (n = 1). As unplanned surgeries, curettage, with or without bone graft, was performed in 26 patients; internal fixation was performed in 7; spinal surgery in 5; arthroplasty in 4; and arthroscopy in one. Thirty-eight patients received additional standard treatments. Thirty-four of these patients underwent surgical tumor resections, including amputation (n = 10), and the remaining 4 received radiotherapy or carbon ion radiotherapy as additional standard treatments. The 5-year disease-specific survival (DSS) rates in patients with osteosarcoma, Ewing sarcoma, and chondrosarcoma were 65.5%, 58.3%, and 72.9%, respectively. Twelve (27.9%) patients developed local recurrences (LR); among the total 43 patients studied, the 5-year DSS rates were significantly worse for those who developed LR compared to those who did not (p = 0.03). The 5-year DSS rates in patients with and without LR were 44% and 73.8%, respectively. Conclusion: We recommend that patients who have undergone unplanned surgery be administered standard treatment, including the option of amputation because herein, LR was shown to be a risk factor for decreased DSS.

DOI： 10.2147/CMAR.S270178

【スポーツ診療における画像診断-医療安全上必要なコツと落とし穴-】スポーツ外傷・障害と間違えやすい病変

尾崎敏文, 中田英二, 長谷井嬢, 国定俊之

関節外科 38 ( 11 ) 1142 - 1150 2019年11月

記述言語：日本語出版者・発行元：(株)メジカルビュー社

スポーツを活発に行う年齢層が骨・軟部腫瘍の好発年齢と一致しているため,スポーツ外傷や障害と骨・軟部腫瘍との鑑別診断は重要である。それらの病変のなかには,(1)偶然発見されたX線像に写った無症候性の病変,(2)疼痛などの症状を伴い骨腫瘍疑いと紹介されてきたが骨腫瘍ではなかった病変,そして(3)骨腫瘍疑いで紹介されてきて真の治療を要する骨腫瘍であった症例などがある。スポーツ外傷・障害を診断するうえで骨腫瘍の知識は重要であるが,それに加えて,外傷,骨折,炎症性疾患など整形外科疾患全般の基本知識も重要である。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00282&link_issn=&doc_id=20191025090004&doc_link_id=10.18885%2FJ00282.2020041696&url=https%3A%2F%2Fdoi.org%2F10.18885%2FJ00282.2020041696&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

顆粒細胞腫における液胞型ATPアーゼ複合体の高頻度変異の同定

関水壮哉, 吉田朗彦, 三谷幸代, 浅野尚文, 平田真, 久保崇, 平賀博明, 米本司, 河本旭哉, 中紀文, 船内雄生, 西田佳弘, 朴木寛弥, 河野博隆, 土屋弘行, 国定俊之, 松田浩一, 稲垣克記, 川井章, 市川仁

日本整形外科学会雑誌 93 ( 6 ) S1425 - S1425 2019年6月

Frequent mutations of genes encoding vacuolar H+ -ATPase components in granular cell tumors. 査読国際誌

Masaya Sekimizu, Akihiko Yoshida, Sachiyo Mitani, Naofumi Asano, Makoto Hirata, Takashi Kubo, Fumito Yamazaki, Hiromi Sakamoto, Mamoru Kato, Naohiro Makise, Taisuke Mori, Naoya Yamazaki, Shigeki Sekine, Ichiro Oda, Shun-Ichi Watanabe, Hiroaki Hiraga, Tsukasa Yonemoto, Teruya Kawamoto, Norifumi Naka, Yuki Funauchi, Yoshihiro Nishida, Kanya Honoki, Hirotaka Kawano, Hiroyuki Tsuchiya, Toshiyuki Kunisada, Koichi Matsuda, Katsunori Inagaki, Akira Kawai, Hitoshi Ichikawa

Genes, chromosomes & cancer 58 ( 6 ) 373 - 380 2019年6月

記述言語：英語

Granular cell tumors (GCTs) are rare mesenchymal tumors that exhibit a characteristic morphology and a finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss-of-function mutations of ATP6AP1 and ATP6AP2 were described. Thus, we performed whole-exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples. From these genomic analyses, we identified mutations in genes encoding vacuolar H+ -ATPase (V-ATPase) components, including ATP6AP1 and ATP6AP2, in 33 (65%) GCTs. ATP6AP1 and ATP6AP2 mutations were found in 23 (45%) and 2 (4%) samples, respectively, and all were truncating or splice site mutations. In addition, seven other genes encoding V-ATPase components were also mutated, and three mutations in ATP6V0C occurred on the same amino acid (isoleucine 136). These V-ATPase component gene mutations were mutually exclusive, with one exception. These results suggest that V-ATPase function is impaired in GCTs not only by loss-of-function mutations of ATP6AP1 and ATP6AP2 but also through mutations of other subunits. Our findings provide additional support for the hypothesis that V-ATPase dysfunction promotes GCT tumorigenesis.

DOI： 10.1002/gcc.22727

悪性骨盤腫瘍患者に対する患肢温存術後のADLとQOLについて術後9年後のインタビューより

岡佳純, 妹尾勝利, 堅山佳美, 国定俊之, 千田益生

The Japanese Journal of Rehabilitation Medicine 56 ( 特別号 ) 3 - 4 2019年5月

Temporary External Fixation Can Stabilize Hip Transposition Arthroplasty After Resection of Malignant Periacetabular Bone Tumors. 査読国際誌

Kunisada T, Fujiwara T, Hasei J, Nakata E, Senda M, Ozaki T

Clinical orthopaedics and related research 477 ( 8 ) 1892 - 1901 2019年4月

Mini-open excision of osteoid osteoma using intraoperative O-arm/Stealth navigation. 査読

Fujiwara T, Kunisada T, Takeda K, Hasei J, Nakata E, Mochizuki Y, Kiyono M, Yoshida A, Ozaki T

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 24 ( 2 ) 337 - 341 2019年3月

Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects. 査読国際誌

Uehara T, Eikawa S, Nishida M, Kunisada Y, Yoshida A, Fujiwara T, Kunisada T, Ozaki T, Udono H

International immunology 31 ( 4 ) 187 - 198 2019年3月

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: a study protocol. 査読

Takeuchi A, Nomura A, Yamamoto N, Hayashi K, Igarashi K, Tandai S, Kawai A, Matsumine A, Miwa S, Nishida Y, Nakamura T, Terauchi R, Hoshi M, Kunisada T, Endo M, Yoshimura K, Murayama T, Tsuchiya H

BMC musculoskeletal disorders 20 ( 1 ) 68 2019年2月

Sub-deltoid approach for removal of large lipoma around the proximal humerus: A report of three cases. 査読

Hasei J, Kunisada T, Nakata E, Ozaki T

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 6 ) 1147 - 1151 2019年2月

Regeneration of the Fibula with Unidirectional Porous Hydroxyapatite. 国際誌

Koji Demiya, Toshiyuki Kunisada, Eiji Nakata, Joe Hasei, Toshifumi Ozaki

Case reports in orthopedics 2019 9024643 - 9024643 2019年

記述言語：英語

A fibula graft is one of the most common orthopedic procedures for reconstruction of a bone defect, and some complications related to persistent defects of the fibula have been reported previously. We believe that regeneration of the fibula may be critical for postoperative function and prevention of complications. This report describes a 9-year-old female with Ewing sarcoma of the pelvis who was treated with the double-barrel fibula grafts for pelvic bone defect following tumor resection. The defect after fibular resection was filled with unidirectional porous hydroxyapatite (UDPHAp) implants. A plain radiograph revealed new bone formation and a callus-like structure at one month after surgery and bony union between each UDPHAp implant 5 months after surgery. Resorption of implanted UDPHAp was identified, and partial remodeling of the bone marrow cavity could be seen 1 year 2 months after surgery. A radiograph at final follow-up (5 years 10 months after surgery) demonstrated almost complete absorption of the implanted UDPHAp and clear formation of the cortex and bone marrow in the resected part of the fibula. The patient is able to walk well without any walking supports and to take part in sports activities.

DOI： 10.1155/2019/9024643

骨・軟部腫瘍における新規分子・細胞標的粘液線維肉腫における分泌型microRNA-1260bは腫瘍周囲微小環境に作用し浸潤を促進する

Clinical features and treatment outcome of desmoid-type fibromatosis: based on a bone and soft tissue tumor registry in Japan 査読

Nishida Y, Kawai A, Toguchida J, Ogose A, Ae K, Kunisada T, Matsumoto Y, Matsunobu T, Takahashi K, Nishida K, Ozaki T

International Journal of Clinical Oncology 24 1498 - 1505 2019年

Identification of Circulating Exosomal Marker in Synovial Sarcoma

Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Masahiro Kiyono, Yusuke Mochizuki, Koji Demiya, Joe Hasei, Toshiyuki Kunisada, Yusuke Yoshioka, Koji Ueda, Takahiro Ochiya, Toshifumi Ozaki

CANCER SCIENCE 109 570 - 570 2018年12月

Injury patterns of medial meniscus posterior root tears. 査読国際誌

Furumatsu T, Okazaki Y, Okazaki Y, Hino T, Kamatsuki Y, Masuda S, Miyazawa S, Nakata E, Hasei J, Kunisada T, Ozaki T

Orthopaedics & traumatology, surgery & research : OTSR 105 ( 1 ) 107 - 111 2018年11月

Intraoperative O-arm-navigated resection in musculoskeletal tumors. 査読

Fujiwara T, Kunisada T, Takeda K, Hasei J, Nakata E, Nakahara R, Yoshida A, Ozaki T

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 23 ( 6 ) 1045 - 1050 2018年11月

Is immunohistochemical staining for β-catenin the definitive pathological diagnostic tool for desmoid-type fibromatosis?: a multi-institutional study. 査読国際誌

Koike H, Nishida Y, Kohno K, Shimoyama Y, Motoi T, Hamada S, Kawai A, Ogose A, Ozaki T, Kunisada T, Matsumoto Y, Matsunobu T, Ae K, Gokita T, Sakai T, Shimizu K, Ishiguro N

Human pathology 84 155 - 163 2018年10月

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study. 査読国際誌

Urakawa H, Yonemoto T, Matsumoto S, Takagi T, Asanuma K, Watanuki M, Takemoto A, Naka N, Matsumoto Y, Kawai A, Kunisada T, Kubo T, Emori M, Hiraga H, Hatano H, Tsukushi S, Nishida Y, Akisue T, Morii T, Takahashi M, Nagano A, Yoshikawa H, Sato K, Kawano M, Hiraoka K, Tanaka K, Iwamoto Y, Ozaki T

World journal of surgical oncology 16 ( 1 ) 160 - 160 2018年8月

森田卓也, 藤原智洋, 吉田晶, 清野正普, 横尾賢, 小松原将, 望月雄介, 長谷井嬢, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 8 ) S1709 - S1709 2018年8月

骨肉腫における細胞内外microRNA-25-3p発現の機能解析

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 8 ) S1813 - S1813 2018年8月

骨肉腫の細胞内外microRNA-25-3p発現異常の腫瘍学的意義

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 中田英二, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 92 ( 6 ) S1460 - S1460 2018年6月

前腕悪性腫瘍に対する術後の作業療法を施行した1例

岡佳純, 松山宜之, 堅山佳美, 国定俊之, 千田益生

The Japanese Journal of Rehabilitation Medicine 55 ( 特別号 ) 3 - 1 2018年5月

Clinical and Functional Significance of Intracellular and Extracellular microRNA-25-3p in Osteosarcoma. 査読

Yoshida A, Fujiwara T, Uotani K, Morita T, Kiyono M, Yokoo S, Hasei J, Nakata E, Kunisada T, Ozaki T

Acta medica Okayama 72 ( 2 ) 165 - 174 2018年4月

【運動器画像診療の最前線】部位別・疾患別画像診療の最前線骨腫瘍の画像診療

中田英二, 国定俊之, 長谷井嬢, 藤原智洋, 尾崎敏文

関節外科 37 ( 4月増刊 ) 130 - 143 2018年4月

記述言語：日本語出版者・発行元：(株)メジカルビュー社

＜画像診療のポイント＞●骨腫瘍の診療において、画像検査は鑑別診断や治療効果判定だけではなく、手術にも有用である。●鑑別診断について、初診医は一般整形外科医であることが多く、悪性を疑う所見を見逃さないことが重要である。●骨腫瘍にはそれぞれ特徴的な年齢分布や好発部位があり、年齢や既往歴などの臨床情報も踏まえ、複数の画像検査の情報を組み合わせて診断を行う。●単純X線像の読影では、腫瘍の局在と性状に注目する。●CTは、単純X線検査では評価が困難な部位の診断、微細な石灰化や骨化の有無の検出などを調べるのに適している。また、三次元的に骨病変を評価することができ、術前計画にも有用である。さらに、近年はコンピュータ支援手術により術中に短時間で高画質の2D・3D画像が取得でき、画像データをナビゲーションシステムに送信することで、より低侵襲かつ安全で確実な手術が可能となっている。●MRIは優れたコントラスト分解能をもち、腫瘍の進展や質的診断、治療効果判定などに有用である。●PET/CTは、良悪性の鑑別診断、病期診断、治療効果判定に有用である。●各画像検査には長所と短所があるため、その特徴を理解しておくことが重要である。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00282&link_issn=&doc_id=20180406150013&doc_link_id=10.18885%2FJ00282.2018192551&url=https%3A%2F%2Fdoi.org%2F10.18885%2FJ00282.2018192551&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

脊椎に原発した骨肉腫の5例

塩崎泰之, 瀧川朋亨, 三澤治夫, 尾崎敏文, 中田英二, 国定俊之

中国・四国整形外科学会雑誌 30 ( 1 ) 79 - 82 2018年4月

記述言語：日本語出版者・発行元：中国・四国整形外科学会

当院で経験した脊椎原発の骨肉腫5例(男性2例、女性3例、診断時平均年齢52歳)について検討した。発生高位はT1が1例、L2が1例、L3が1例、L5が2例であった。初診時の症状は腰椎発生の3例では全例に腰痛が認められ、2例に下肢不全麻痺が合併していた。胸椎発生の2例では、それぞれ背部痛と上肢痛を認められた。治療は全摘出術を2例、重粒子線治療を3例に行った。また、化学療法は4例に行った。予後は、治療中の2例を除き、3例は診断後平均66ヵ月で死亡していた。

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02438&link_issn=&doc_id=20180621090018&doc_link_id=%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcm4ortho%2F2018%2F003001%2F018%2F0079-0082%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

肉腫進行例の新しい診療システムサルコーマセンター設立と腫瘍内科医との連携

国定俊之, 田端雅弘, 山根弘路, 中田英二, 長谷井嬢, 尾崎敏文

中部日本整形外科災害外科学会雑誌 61 ( 春季学会 ) 88 - 88 2018年3月

Patients with osteosarcoma and soft tissue sarcoma might become “cancer refugees” in some japanese regional cities 査読

Hiromichi Yamane, Toshiyuki Kunisada, Toshifumi Ozaki, Nobuaki Ochi, Yoshihiro Honda, Yasunari Nagasaki, Nozomu Nakagawa, Tomoko Yamagishi, Hidekazu Nakanishi, Nagio Takigawa

Cancer Management and Research 10 353 - 359 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Dove Medical Press Ltd

Purpose: “Rare cancer” is defined as malignancy with a disease prevalence (age-adjusted incidence rate) of less than six per 100,000 population. Proper treatments which these patients need cannot always be performed unless they find dedicated facilities. Patients tend to be desperate, searching for advice and care. Thus, they are called “cancer refugees”. Osteosarcoma and soft tissue sarcoma (OS/STS) are representative rare cancers in Japan. We conducted a retrospective analysis of patients with OS/STS to improve the current treatment modalities in a Japanese regional city. Patients and methods: Twenty-one patients with OS/STS who were hospitalized to receive standard chemotherapy or palliative treatment were enrolled between October 2011 and January 2017. Patients with non-Hodgkin’s lymphoma (NHL) and advanced cancer who were treated in the palliative care unit (PCU) of the Kawasaki Medical School General Medical Center were recruited as the control groups. We analyzed the difference in residential area between patients with OS/STS and the control groups. Results: Approximately one-third of patients with OS/STS were referred from hospitals outside of Okayama prefecture. The ratio of patients with OS/STS referred from Okayama city and/or the same medical administration area of Okayama prefecture was lower than that of patients with NHL and advanced cancer who were treated in the PCU. Conclusion: Because the medical environment of patients with OS/STS in Japanese local cities has not been consolidated, completing medical care within the patient’s own medical administration area is difficult. Thus, some patients with OS/STS may become “cancer refugees” who are unable to receive standard therapy near their residence.

DOI： 10.2147/CMAR.S155282

Molecular radiosensitization of p53-armed telomerase-dependent oncolytic adenovirus against human soft-tissue sarcoma

Tadashi Komatsubara, Hiroshi Tazawa, Yusuke Mochizuki, Kazuhisa Sugiu, Toshinori Omori, Yasuaki Yamakawa, Syuhei Osaki, Joe Hasei, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER SCIENCE 109 454 - 454 2018年1月

Liquid biopsy using tumor-derived exosomes for Ewing sarcoma patients

Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Shintaro Iwata, Yusuke Yoshioka, Koji Ueda, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Takahiro Ochiya, Toshifumi Ozaki

CANCER SCIENCE 109 312 - 312 2018年1月

A rare manifestation of extraskeletal myxoid chondrosarcoma with a huge expanding hematoma 査読

Toshinori Omori, Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Aki Yoshida, Hiroyuki Yanai, Toshifumi Ozaki

Journal of Orthopaedic Science 2018年

Circulating MicroRNA-92b-3p as a Novel Biomarker for Monitoring of Synovial Sarcoma 査読

Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Kunihiko Numoto, Yutaka Nezu, Tsukasa Yonemoto, Takeshi Ishii, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

SCIENTIFIC REPORTS 7 ( 1 ) 14634 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

DOI： 10.1038/s41598-017-12660-5

地方都市における希少がん標準的化学療法の取り組み骨軟部腫瘍化学療法の現状

山根弘路, 越智宣昭, 本多宣裕, 山岸智子, 中川望, 長崎泰有, 国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文, 瀧川奈義夫

日本癌治療学会学術集会抄録集 55回 P42 - 4 2017年10月

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction 査読

Yasuaki Yamakawa, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Cancer Science 108 ( 9 ) 1870 - 1880 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Blackwell Publishing Ltd

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.

DOI： 10.1111/cas.13316

Factors associated with the decision of operative procedure for proximal femoral bone metastasis: Questionnaire survey to institutions participating the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group 査読

Nobuhito Araki, Hirokazu Chuman, Tomoya Matsunobu, Kazuhiro Tanaka, Hirohisa Katagiri, Toshiyuki Kunisada, Toru Hiruma, Hiroaki Hiraga, Hideo Morioka, Hiroshi Hatano, Kunihiro Asanuma, Yoshihiro Nishida, Koji Hiraoka, Takeshi Okamoto, Satoshi Abe, Munenori Watanuki, Takeshi Morii, Hideshi Sugiura, Yukihiro Yoshida, Takatoshi Ohno, Hidetatsu Outani, Koichiro Yokoyama, Shoji Shimose, Haruhiko Fukuda, Yukihide Iwamoto

JOURNAL OF ORTHOPAEDIC SCIENCE 22 ( 5 ) 938 - 945 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER JAPAN KK

Background: Pathological fracture of the proximal femur is a main cause of cancer patients losing their ability to walk. Although both osteosynthetic devices (predominantly intramedullary nails) and prosthetic replacement have been widely performed for treatment, controversies exist regarding which procedure should be used for the various conditions. In order to decide the eligibility criteria of a planned randomized prospective study about the treatment of pathological fractures of the proximal femur, we assessed the factors affecting the selection of operative procedures using questionnaires sent to the members of the Bone and Soft Tissue Tumor Study Group (BSTTSG) of the Japan Clinical Oncology Group (JCOG).
Methods: Questionnaire surveys to evaluate (1) the priority levels of the factors, (2) the equipoise range of each factor in situations where either procedure could be applied, (3) risk and benefit of each procedure, and (4) the degree of bone destruction affecting the selection of operative procedures, were sent to 26 institutions.
Results: Over 80% of the institutions answered. Orthopaedic surgeons of BSTTSG decided on the procedure according to the following factors in descending order: life expectancy, performance status before fracture, the degree of bone destruction, walking ability before fracture, general complications, the number of bone metastases in other sites, and the visceral metastasis status. With regard to bone destruction, (1) the involvement of the head, neck, calcar, and intertrochanteric region, (2) transverse destruction >1/2, and (3) soft-tissue tumor extension, were the factors that led to the choice of prosthesis treatment.
Conclusions: Using these identified factors, the inclusion criteria for the prospective randomized study of the surgical treatment of metastatic bone tumors of the proximal femur were optimized. The evaluation system about the bone destruction of metastases needs to be refined through the following prospective randomized study. (C) 2017 The Authors. Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.jos.2017.05.012

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction 査読

CANCER SCIENCE 108 ( 9 ) 1870 - 1880 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

DOI： 10.1111/cas.13316

未来人が拓く整形外科医療骨盤骨腫瘍に対する切除後再建法

悪性骨軟部腫瘍に対する治療の進歩術中ナビゲーションシステムを併用した悪性骨軟部腫瘍手術

国定俊之, 藤原智洋, 長谷井嬢, 瀧川朋亨, 尾崎敏文

中部日本整形外科災害外科学会雑誌 60 ( 秋季学会 ) 48 - 48 2017年9月

Ewing肉腫におけるエクソソームを標的とした体液診断法の確立

吉田晶, 藤原智洋, 魚谷弘二, 岩田慎太郎, 吉岡祐亮, 植田幸嗣, 森田卓也, 清野正普, 横尾賢, 長谷井嬢, 国定俊之, 落谷孝広, 尾崎敏文

日本癌学会総会記事 76回 P - 1289 2017年9月

長谷井嬢, 国定俊之, 藤原智洋, 中田英二, 尾崎敏文

中国・四国整形外科学会雑誌 29 ( 3 ) 329 - 329 2017年9月

骨肉腫細胞内と分泌エクソソーム内におけるmicroRNA発現の相違と患者血清エクソソーム内の発現と臨床的相関性

清野正普, 藤原智洋, 吉田晶, 森田卓也, 横尾賢, 小松原将, 望月雄介, 出宮浩二, 長谷井嬢, 国定俊之, 尾崎敏文

日本癌学会総会記事 76回 P - 2045 2017年9月

軟部肉腫に対するp53発現テロメラーゼ依存型腫瘍融解アデノウイルスの放射線効果増強

小松原将, 田澤大, 望月雄介, 杉生和久, 大森敏規, 山川泰明, 尾崎修平, 長谷井嬢, 藤原智洋, 国定俊之, 浦田泰生, 尾崎敏文, 藤原俊義

日本癌学会総会記事 76回 J - 2008 2017年9月

悪性骨腫瘍切除後の機能再建手術

尾崎敏文, 中田英二, 藤原智洋, 長谷井嬢, 国定俊之

The Japanese Journal of Rehabilitation Medicine 54 ( 秋季特別号 ) S138 - S138 2017年9月

粘液線維肉腫由来エクソソーム中microRNAプロファイリングの特定と機能解析

森田卓也, 藤原智洋, 吉田晶, 清野正晋, 横尾賢, 長谷井嬢, 国定俊之, 尾崎敏文

日本癌学会総会記事 76回 P - 2295 2017年9月

骨肉腫細胞内と分泌エクソソーム内におけるmicroRNA発現プロファイリングの相違と患者循環エクソソーム内の発現評価

清野正普, 藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 杉生和久, 小松原将, 望月雄介, 長谷井嬢, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1525 - S1525 2017年8月

Ewing肉腫における腫瘍由来exosomeを標的としたliquid biopsy法の確立

魚谷弘二, 藤原智洋, 吉田晶, 岩田慎太郎, 森田卓也, 清野正普, 長谷井嬢, 国定俊之, 吉岡祐亮, 植田幸嗣, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1713 - S1713 2017年8月

腫瘍融解ウイルスの骨・軟部腫瘍組織に対する感染効率の評価

吉田晶, 魚谷弘二, 藤原智洋, 長谷井嬢, 森田卓也, 清野正普, 杉生和久, 小松原将, 望月雄介, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1823 - S1823 2017年8月

ドキソルビシン耐性骨肉腫細胞に対するp53発現腫瘍融解アデノウイルスによるMDR1発現抑制を介した薬剤耐性克服機序の検討

杉生和久, 田澤大, 望月雄介, 小松原将, 大森敏規, 山川泰明, 吉田晶, 長谷井嬢, 藤原智洋, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1523 - S1523 2017年8月

p53発現腫瘍融解アデノウイルスによる軟部肉腫に対する放射線治療併用効果の検討

小松原将, 望月雄介, 杉生和久, 大森敏規, 長谷井嬢, 吉田晶, 藤原智洋, 国定俊之, 浦田泰生, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1499 - S1499 2017年8月

悪性骨・軟部腫瘍転移制御への道粘液線維肉腫における分泌型microRNAは腫瘍の浸潤性と関連しているか

森田卓也, 藤原智洋, 魚谷弘二, 吉田晶, 清野正普, 杉生和久, 小松原将, 望月雄介, 長谷井嬢, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 91 ( 8 ) S1709 - S1709 2017年8月

術後10年以上経過した腫瘍用人工関節の長期治療成績

長谷井嬢, 望月雄介, 吉田晶, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1382 - S1382 2017年6月

骨肉腫切除後のGrowing Kotz人工関節置換症例における長期フォロー成績

望月雄介, 長谷井嬢, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1252 - S1252 2017年6月

骨肉腫細胞から分泌されるエクソソームは腫瘍進展においてどのような役割を担っているか

清野正普, 藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 杉生和久, 小松原将, 望月雄介, 長谷井嬢, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1320 - S1320 2017年6月

術中CTナビゲーションシステムの良性骨腫瘍手術における有用性

藤原智洋, 国定俊之, 長谷井嬢, 森田卓也, 小松原将, 清野正普, 望月雄介, 吉田晶, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1290 - S1290 2017年6月

踵骨原発骨腫瘍に対する治療成績の検討

沖田駿治, 藤原智洋, 国定俊之, 長谷井嬢, 小松原将, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1331 - S1331 2017年6月

Ewing肉腫患者の血中を循環する腫瘍由来exosomeの表面抗原を標的とした体液診断法の開発

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 清野正普, 杉生和久, 小松原将, 望月雄介, 国定俊之, 長谷井嬢, 吉岡祐亮, 植田幸嗣, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1321 - S1321 2017年6月

軟部肉腫に対する腫瘍融解アデノウイルスによる放射線治療増感効果の検討

小松原将, 大森敏規, 望月雄介, 杉生和久, 長谷井嬢, 吉田晶, 藤原智洋, 国定俊之, 浦田泰生, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1385 - S1385 2017年6月

p53発現腫瘍融解アデノウイルスの薬剤耐性骨肉腫細胞に対する抗腫瘍効果と耐性克服メカニズムの検討

杉生和久, 田澤大, 望月雄介, 小松原将, 大森敏規, 山川泰明, 吉田晶, 長谷井嬢, 藤原智洋, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1385 - S1385 2017年6月

粘液線維肉腫患者における分泌型microRNAの特定

森田卓也, 藤原智洋, 魚谷弘二, 吉田晶, 清野正晋, 杉生和久, 小松原将, 望月雄介, 長谷井嬢, 国定俊之, 落合孝広, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1394 - S1394 2017年6月

滑膜肉腫における分泌型microRNAの細胞外安定性の解析

魚谷弘二, 藤原智洋, 吉田晶, 森田卓也, 清野正普, 長谷井嬢, 国定俊之, 根津悠, 岩田慎太郎, 川井章, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1355 - S1355 2017年6月

切除縁評価と骨・軟部肉腫手術再発悪性骨・軟部腫瘍に対する手術切除縁と治療成績

国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文

日本整形外科学会雑誌 91 ( 6 ) S1346 - S1346 2017年6月

Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma 査読

Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Yutaka Nezu, Eisuke Kobayashi, Akihiko Yoshida, Takenori Uehara, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Ken Takeda, Toshiyuki Kunisada, Machiko Kawamura, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

ONCOTARGET 8 ( 20 ) 33375 - 33392 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IMPACT JOURNALS LLC

Background: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma.
Methods: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort.
Results: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase.
Conclusions: Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

DOI： 10.18632/oncotarget.16498

骨肉腫患者の組織ならびに血中におけるoncogenic miR-25-3pの臨床病理学的意義

鎖骨骨切りにより切除可能となった腕神経叢発生脂肪性腫瘍の治療経験

横尾賢, 国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文

中部日本整形外科災害外科学会雑誌 60 ( 春季学会 ) 193 - 193 2017年4月

藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 清野正普, 国定俊之, 根津悠, 小林英介, 川井章, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 91 ( 3 ) S707 - S707 2017年3月

骨・軟部肉腫切除術における感染リスクファクターの検討

長谷井嬢, 望月雄介, 小松原将, 国定俊之, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

日本整形外科学会雑誌 91 ( 2 ) S598 - S598 2017年3月

肩関節周辺悪性骨腫瘍切除後の肩関節再建手術腫瘍型上腕骨人工骨頭置換術に対する軟部組織再建術

国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文

日本整形外科学会雑誌 91 ( 2 ) S400 - S400 2017年3月

骨・軟部腫瘍における術中CTナビゲーション手術の正確性と臨床評価

藤原智洋, 国定俊之, 長谷井嬢, 吉田晶, 尾崎敏文

日本整形外科学会雑誌 91 ( 3 ) S711 - S711 2017年3月

Verification of Implant Surface Modification by a Novel Processing Method

Okada Yoshiki, Abe Nobuhiro, Hisamori Noriyuki, Kaneeda Toshiaki, Moriyama Shigeaki, Ohmori Hitoshi, Mizutani Masayoshi, Yanai Hiroyuki, Nakashima Yoshio, Yokoyama Yusuke, Ozaki Toshifumi

Acta Medica Okayama 71 ( 1 ) 49 - 57 2017年2月

記述言語：英語出版者・発行元：Okayama University Medical School

Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact.

DOI： 10.18926/AMO/54825

CiNii Books

Efficacy of Trabectedin in Patients with Advanced Translocation-Related Sarcomas: Pooled Analysis of Two Phase II Studies 査読

Mitsuru Takahashi, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Masashi Shimura, Akira Kawai

ONCOLOGIST 22 ( 8 ) 979 - 988 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Background. Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m(2) trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS).
Methods. Trabectedin was administered on day one of a 21-day cycle. Efficacy was assessed using progression-free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (<1,000/mu L, >= 1,000/mu L) or number of previous chemotherapy regimens (0, 1, 2, >= 3 regimens), and a Weibull parametric model was used to estimate the numerical relationship between lymphocyte count and PFS and OS.
Results. Median PFS and OS in overall patients were 5.6 (95% confidence interval [CI]: 4.1-7.3) and 17.5 months (95% CI: 12.6-23.6), respectively. PFS in the myxoid and round-cell liposarcoma (MRCL) group (7.4 months [95% CI: 5.6-11.1]) was longer than in the other subtypes. The response rate was also highest in the MRCL group. Median OS was longer in patients with baseline lymphocyte counts >= 1,000/mu L than in those with counts of <1,000/mu L, but median PFS was not different between the two subgroups.
Conclusion. Our updated and pooled data showed that trabectedin exerted prolonged disease control and antitumor effects in patients with advanced TRS, especially in MRCL. We consider that the subgroup analyses also provide important information for trabectedin treatment in patients with TRS.

DOI： 10.1634/theoncologist.2016-0064

Neurological Recovery after Posterior Spinal Surgery in Patients with Metastatic Epidural Spinal Cord Compression 査読

Noriyuki Watanabe, Yoshihisa Sugimoto, Masato Tanaka, Tetsuro Mazaki, Shinya Arataki, Tomoyuki Takigawa, Masaki Kataoka, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 70 ( 6 ) 449 - 453 2016年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Metastatic epidural spinal cord compression (MESCC) is a common complication in patients with a malignant tumor, but it is difficult to decide the proper time to perform the necessary surgery. Here we analyzed the prognostic factors for postoperative walking ability. We retrospectively reviewed the cases of 112 MESCC patients treated surgically at our institute and divided them into ambulatory (n = 88) and non-ambulatory (n = 24) groups based on their American Spinal Injury Association (ASIA) Impairment Scale grades at the final follow-up. We also classified the patients preoperatively using the revised Tokuhashi score. We assessed the correlation between preoperative or intraoperative factors and postoperative walking ability in both groups. Of the 10 patients classified preoperatively as grade A or B, 2 (20) were ambulatory at the final follow-up. Of the 102 patients classified preoperatively as grade C, D or E, 86 (84) were ambulatory at the final follow-up (p < 0.001). There were no significant differences between the groups in the average total Tokuhashi score. Our analysis revealed that the severity of paralysis significantly affects neurological recovery in patients with MESCC. Patients with MESCC should receive surgery before the preoperative ASIA Impairment Scale grade falls below grade C.

DOI： 10.18926/AMO/54807

骨腫瘍切除後の骨欠損に対する配向連通気孔構造を有する人工骨移植の治療経験

清野正普, 国定俊之, 藤原智洋, 長谷井嬢, 杉生和久, 魚谷弘二, 森田卓也, 小松原将, 望月雄介, 尾崎敏文

移植 51 ( 6 ) 527 - 527 2016年12月

腫瘍融解ウイルス療法による骨肉腫のABC Transporterを介した薬剤耐性の克服

杉生和久, 田澤大, 長谷井嬢, 尾崎修平, 山川泰明, 大森敏規, 小松原将, 望月雄介, 藤原智洋, 国定俊之, 浦田泰生, 尾崎敏文, 藤原俊義

日本癌学会総会記事 75回 J - 3020 2016年10月

粘液線維肉腫におけるcirculating cell-free microRNAの特定

森田卓也, 藤原智洋, 魚谷弘二, 吉田晶, 清野正晋, 杉生和久, 小松原将, 望月雄介, 国定俊之, 落谷孝広, 尾崎敏文

日本癌学会総会記事 75回 P - 2325 2016年10月

体液診断への応用を目指したEwing肉腫由来分泌エクソソーム表面マーカーの解析

吉田晶, 魚谷弘二, 藤原智洋, 森田卓也, 清野正普, 長谷井嬢, 国定俊之, 吉岡祐亮, 植田幸嗣, 落谷孝広, 尾崎敏文

日本癌学会総会記事 75回 P - 2319 2016年10月

Circulating microRNAの骨肉腫における新規バイオマーカーとしての可能性

藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 清野正晋, 杉生和久, 小松原将, 長谷井嬢, 国定俊之, 根津悠, 川井章, 落谷孝広, 尾崎敏文

日本癌学会総会記事 75回 P - 3084 2016年10月

滑膜肉腫の新規バイオマーカー開発を目指した循環型cell-free microRNAの特定と検証

魚谷弘二, 藤原智洋, 吉田晶, 森田卓也, 杉生和久, 小松原将, 清野正普, 根津悠, 国定俊之, 川井章, 岩田慎太郎, 落谷孝広, 尾崎敏文

日本癌学会総会記事 75回 P - 2327 2016年10月

軟部肉腫に対するテロメラーゼ標的型腫瘍融解アデノウイルスの放射線効果増強

小松原将, 大森敏規, 田澤大, 杉生和久, 望月雄介, 山川泰明, 尾崎修平, 長谷井嬢, 藤原智洋, 国定俊之, 浦田泰生, 尾崎敏文, 藤原俊義

日本癌学会総会記事 75回 P - 3306 2016年10月

骨肉腫細胞内と細胞外分泌エクソソーム内のmicroRNA発現プロファイリングは転移能の違いによりどのように異なるか

清野正普, 藤原智洋, 魚谷弘二, 吉田晶, 杉生和久, 小松原将, 望月雄介, 長谷井嬢, 國定俊之, 尾崎敏文

日本癌学会総会記事 75回 P - 3085 2016年10月

ヒト軟骨組織におけるTWIST1の異化反応誘導とOA発症メカニズム

長谷井嬢, 藤原智洋, 国定俊之, 福田寛二, 浅原弘嗣, 尾崎敏文

中部日本整形外科災害外科学会雑誌 59 ( 秋季学会 ) 245 - 245 2016年9月

踵骨発生原発性骨腫瘍に対する治療成績

小松原将, 藤原智洋, 国定俊之, 長谷井嬢, 尾崎敏文

中国・四国整形外科学会雑誌 28 ( 3 ) 409 - 409 2016年9月

類骨骨腫に対するラジオ波焼灼術の治療成績

藤原智洋, 国定俊之, 長谷井嬢, 郷原英夫, 金澤右, 尾崎敏文

中国・四国整形外科学会雑誌 28 ( 3 ) 410 - 410 2016年9月

O-armによる術中ナビゲーションシステムを併用した悪性骨軟部腫瘍手術の精度

藤原智洋, 国定俊之, 長谷井嬢, 清野正晋, 望月雄介, 尾崎敏文

中部日本整形外科災害外科学会雑誌 59 ( 秋季学会 ) 148 - 148 2016年9月

ナビゲーションを利用した類骨骨腫の小侵襲切除術

国定俊之, 藤原智洋, 長谷井嬢, 小松原将, 森田卓也, 尾崎敏文

中部日本整形外科災害外科学会雑誌 59 ( 秋季学会 ) 97 - 97 2016年9月

岡山大学骨軟部腫瘍グループの活動

国定俊之, 藤原智洋, 長谷井嬢, 尾崎敏文

中国・四国整形外科学会雑誌 28 ( 3 ) 372 - 372 2016年9月

臨床検体を用いた腫瘍融解アデノウイルスの骨・軟部腫瘍への適応に関する検討

吉田晶, 魚谷弘二, 藤原智洋, 長谷井嬢, 大森敏規, 杉生和久, 小松原将, 森田卓也, 清野正晋, 望月雄介, 武田健, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1627 - S1627 2016年8月

変形性関節症における骨棘形成に対するADAM12の関与

堀田昌宏, 西田圭一郎, 古松毅之, 宮澤慎一, 那須義久, 中原龍一, 藤原智洋, 町田崇博, 竹下歩, 兼田大輔, 前原亜美, 櫻井美和, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1590 - S1590 2016年8月

骨肉腫細胞内と細胞外分泌エクソソーム内のmicroRNA発現プロファイリングはどのように異なるか

清野正普, 藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 杉生和久, 小松原将, 望月雄介, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1801 - S1801 2016年8月

p53発現腫瘍融解アデノウイルスはMDR-1発現を抑制することにより薬剤耐性骨肉腫細胞に対して強力な抗腫瘍効果を示す

杉生和久, 望月雄介, 小松原将, 大森敏規, 山川泰明, 吉田晶, 長谷井嬢, 藤原智洋, 国定俊之, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1554 - S1554 2016年8月

粘液線維肉腫患者血清における分泌型microRNAの特定

森田卓也, 藤原智洋, 魚谷弘二, 吉田晶, 杉生和久, 小松原将, 清野正普, 望月雄介, 根津悠, 国定俊之, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1560 - S1560 2016年8月

Ewing肉腫から分泌されるexosomeの表面蛋白を利用したliquid biopsyの開発

望月雄介, 藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 清野正普, 大森敏規, 杉生和久, 小松原将, 武田健, 国定俊之, 吉岡祐亮, 植田幸嗣, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1559 - S1559 2016年8月

軟部肉腫に対する腫瘍融解アデノウイルスと放射線治療の併用効果の検討

小松原将, 大森敏規, 杉生和久, 森田卓也, 魚谷弘二, 吉田晶, 藤原智洋, 武田健, 国定俊之, 浦田泰生, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1565 - S1565 2016年8月

放射線抵抗性を示す骨・軟部肉腫に対する腫瘍融解アデノウイルスの放射線増感作用

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 杉生和久, 藤原智洋, 吉田晶, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 90 ( 8 ) S1564 - S1564 2016年8月

Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma 査読

Hideo Morioka, Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Mitsuru Takahashi, Tsukasa Yonemoto, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Michiro Susa, Robert Nakayama, Kazumasa Nishimoto, Kazutaka Kikuta, Keisuke Horiuchi, Akira Kawai

BMC CANCER 16 479 2016年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BIOMED CENTRAL LTD

Background: Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study.
Methods: Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review.
Results: The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4-not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3-1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10. 4-26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive.
Conclusions: This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better than previously reported data of TRS. These facts suggest that trabectedin become an important choice of treatment for patients with advanced EMCS or MCS who failed or were intolerable to standard chemotherapy.

DOI： 10.1186/s12885-016-2511-y

Identification of circulating tumor derived microRNA signatures in osteosarcoma

Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Tadashi Komatsubara, Kazuhisa Sugiu, Toshinori Oman, Ken Takeda, Toshiyuki Kunisada, Yutaka Nezu, Akira Kawai, Hirotaka Kanzaki, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

Circulating cell-free microRNA as a novel biomarker for synovial sarcoma patients

Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Takuya Morita, Yutaka Nezu, Tadashi Komatsubara, Kazuhisa Sugiu, Takenori Uehara, Toshinori Omani, Ken Takeda, Toshiyuki Kunisada, Junya Toguchida, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

Tumor suppressor p53 reactivation by oncolytic adenovirus reverses chemoresistance in human osteosarcomas

Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 76 2016年7月

Identification of exosomal surface marker derived from Ewing sarcoma cells

Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Yusuke Yoshioka, Koji Ueda, Takuya Morita, Ken Takeda, Toshiyuki Kunisada, Yutaka Nezu, Hiroyuki Kawashima, Takahiro Ochiya, Toshifumi Ozaki

CANCER RESEARCH 76 2016年7月

骨軟部肉腫切除における感染リスクファクター

望月雄介, 小松原将, 長谷井嬢, 国定俊之, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

日本骨・関節感染症学会プログラム・抄録集 39回 90 - 90 2016年7月

Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas 査読

Shuhei Osaki, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Tsuyoshi Sasaki, Toshiyuki Kunisada, Aki Yoshida, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

SCIENTIFIC REPORTS 6 28953 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.

DOI： 10.1038/srep28953

脊椎に発生したpigmented villonodular synovitisの2例

創外固定を利用した悪性骨盤腫瘍に対する早期リハビリテーション

国定俊之, 藤原智洋, 野田知之, 堅山佳美, 千田益生, 尾崎敏文

The Japanese Journal of Rehabilitation Medicine ( JARM2016 ) I438 - I438 2016年6月

魚谷弘二, 藤原智洋, 瀧川朋亨, 荒瀧慎也, 杉本佳久, 武田健, 国定俊之, 田中雅人, 尾崎敏文

日本整形外科学会雑誌 90 ( 6 ) S1353 - S1353 2016年6月

骨・軟部肉腫に対する腫瘍融解ウイルスの放射線増感作用

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 杉生和久, 藤原智洋, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 90 ( 6 ) S1260 - S1260 2016年6月

骨・軟部腫瘍外科における手術支援ナビゲーションシステムを用いた骨・軟部腫瘍手術

国定俊之, 武田健, 藤原智洋, 瀧川朋亨, 荒瀧慎也, 尾崎敏文

日本整形外科学会雑誌 90 ( 6 ) S1296 - S1296 2016年6月

血清中分泌型microRNAをマーカーとした軟部肉腫の鑑別

吉田晶, 藤原智洋, 魚谷弘二, 森田卓也, 武田健, 国定俊之, 根津悠, 川井章, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 90 ( 6 ) S1275 - S1275 2016年6月

Retrospective inter- and intra-patient evaluation of trabectedin after best supportive care for patients with advanced translocation-related sarcoma after failure of standard chemotherapy 査読

Nobuhito Araki, Shunji Takahashi, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Akira Kawai

EUROPEAN JOURNAL OF CANCER 56 122 - 130 2016年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

Aim: Our randomised phase II study showed the clinical benefit of trabectedin compared with best supportive care (BSC) in patients with advanced translocation-related sarcomas after the failure of standard chemotherapy. The aim of the present study was to evaluate efficacy and safety of trabectedin in the identical patients crossed over to trabectedin after disease progression in the BSC arm of the randomised study.
Patients and methods: This was a single-arm study of the BSC patients of the randomised study in whom disease progressed. Trabectedin (1.2 mg/m(2)) was administered over 24 h on day 1 of a 21-d treatment cycle. The efficacy and safety of trabectedin after BSC were evaluated and retrospectively compared with the results of the randomised study.
Results: Thirty patients crossed over to trabectedin. Median progression-free survival (PFS) was 7.3 months (95% confidence interval [CI]: 2.9-9.1) after crossover compared with 0.9 months (95% CI: 0.9-1.0) at BSC in the randomised study. PFS in the present study was comparable to that of the trabectedin arm in the randomised study. The number of patients with growth modulation index >= 1.33 was 25 (86%). Individual tumour volume was decreased in 11 patients after crossover. Adverse drug reactions (ADRs) were observed in 27 patients (96.4%). ADRs of grade III-IV were mainly bone marrow suppression and abnormal liver functions.
Conclusion: Trabectedin was revealed to be effective and well tolerated in the identical patients crossed over to trabectedin after disease progression in BSC. The present study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121853. (C) 2015 The Authors. Published by Elsevier Ltd.

DOI： 10.1016/j.ejca.2015.12.014

ラジオ波焼灼術(RFA)を行った類骨骨腫の治療成績

術中ナビゲーションを用いて切除し得た脛骨原発phosphaturic mesenchymal tumorの一例

藤原智洋, 国定俊之, 武田健, 西山悠紀, 稲垣兼一, 尾崎敏文

中部日本整形外科災害外科学会雑誌 59 ( 春季学会 ) 171 - 171 2016年3月

国定俊之, 武田健, 藤原智洋, 郷原英夫, 金澤右, 尾崎敏文

日本整形外科学会雑誌 90 ( 3 ) S843 - S843 2016年3月

Circulating microRNAの新規バイオマーカーとしての可能性の検証骨肉腫診療における可能性

藤原智洋, 魚谷弘二, 吉田晶, 森田卓也, 武田健, 国定俊之, 川井章, 根津悠, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 90 ( 3 ) S611 - S611 2016年3月

胞巣状軟部肉腫の特徴的な画像所見

国定俊之, 武田健, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

中部日本整形外科災害外科学会雑誌 59 ( 春季学会 ) 89 - 89 2016年3月

骨・軟部肉腫切除後にプレート固定した自家処理骨移植の治療成績

武田健, 国定俊之, 森田卓也, 小松原将, 魚谷弘二, 杉生和久, 藤原智洋, 杉原進介, 尾崎敏文

日本整形外科学会雑誌 90 ( 2 ) S171 - S171 2016年3月

【3Dモデル・3Dプリンターを利用した整形外科手術】整形外科分野への応用 3D実体モデルを利用した骨・軟部腫瘍手術

武田健, 中原龍一, 原田遼三, 国定俊之, 尾崎敏文

関節外科 35 ( 2 ) 198 - 204 2016年2月

Limb salvage surgery for pelvic osteosarcoma 査読

Toshiyuki Kunisada, Ken Takeda, Tomohiro Fujiwara, Shinsuke Sugihara, Toshifumi Ozaki

Osteosarcoma 135 - 147 2016年1月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

Patients with pelvic osteosarcoma have a poor outcome
treatment is one of the most challenging problems for the orthopedic oncologist. The reconstructive approach varies according to anatomic location, extent of resection, the patient’s functional demands, and individual surgeon preference. The choice of optimal technique for reconstruction after acetabular tumor resection depends on numerous parameters and includes iliofemoral arthrodesis or pseudoarthrodesis, combined use of hip arthroplasty with massive allograft or recycled autograft, and pelvic and saddle prosthesis. The type of reconstruction modality can influence the rate of infection. Hip transposition resulted in the least incidence of complications after resection of the acetabulum, compared to the use of prosthesis or prosthesis and allograft. The absence of large implants and allografts helps reduce surgical time, facilitates closure, and may decrease the incidence of infection and late revision due to implant failure. These can lead to early postoperative systemic treatment and functional recovery and are critical for patients with a high incidence of local recurrence and distant metastases. We believe that resection arthroplasty should be indicated for the patient with acetabular osteosarcoma.

DOI： 10.1007/978-4-431-55696-1_11

骨腫瘍切除後の骨欠損に対する配向連通気孔構造を有した新しい人工骨移植の治療成績

武田健, 国定俊之, 藤原智洋, 尾崎敏文

移植 50 ( 6 ) 666 - 666 2015年12月

Prominent thallium-201 uptake of giant cell tumor of bone : comparison with osteosarcoma

R. Inai, S. Takayoshi, T. Tanaka, Y. Tsuboi, S. Norikane, K. Kojima, A. Tada, T. Kunisada, S. Sato, T. Ozaki, S. Kanazawa

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 42 S783 - S784 2015年10月

Diagnostic value of Thallium-201 scintigraphy in differentiating malignant bone tumors from benign bone lesions 査読

Ryota Inai, Takayoshi Shinya, Akihiro Tada, Shuhei Sato, Tomohiro Fujiwara, Ken Takeda, Toshiyuki Kunisada, Hiroyuki Yanai, Toshifumi Ozaki, Susumu Kanazawa

ANNALS OF NUCLEAR MEDICINE 29 ( 8 ) 674 - 681 2015年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

This retrospective study aims to evaluate the diagnostic capacity of thallium-201 (201Tl) scintigraphy for differentiating malignant bone tumors from benign bone lesions.
Between January 2006 and December 2012, 279 patients with bone lesions (51 malignant and 228 benign) underwent 201Tl scintigraphy before treatment. To evaluate 201Tl uptake, we investigated tumor-to-background contrast (TBC) as well as TBC washout rate (WR). The differences of TBC on early and delayed images and WR were estimated by the Mann-Whitney U test. Receiver operating characteristic (ROC) analyses were used to determine the cut-off TBC values for differentiating malignant bone tumors from benign bone lesions.
There were statistically significant differences in median TBC between malignant tumors and benign lesions. These differences occurred for early imaging (1.57 vs. 0.09, p < 0.001) as well as for delayed imaging (0.83 vs. 0.07, p < 0.001). However, there was no statistical difference in WR between malignant tumors and benign lesions (44 vs. 43 %, NS). The chosen TBC cut-off value was 0.68 for early imaging and 0.38 for delayed imaging. Using these cut-off values, the prediction of malignancy had a 77 % sensitivity, 74 % specificity, and 75 % accuracy for early imaging and an 80 % sensitivity, 76 % specificity, and 77 % accuracy for delayed imaging.
201Tl scintigraphy may have the ability to distinguish malignant bone tumors from benign bone lesions.

DOI： 10.1007/s12149-015-0990-6

腫瘍特異的増殖型ウイルスによる骨・軟部肉腫circulating tumor cell(CTC)検出法の検討

RPN2は骨肉腫の様々な悪性形質を制御し臨床予後を規定する

藤原智洋, 根津悠, 吉田晶, 魚谷弘二, 国定俊之, 武田健, 森田卓也, 小松原将, 杉生和久, 大森敏規, 川井章, 落谷孝広, 尾崎敏文

日本癌学会総会記事 74回 P - 3207 2015年10月

Ewing肉腫に対する新しい診断法のためのエクソソーム表面マーカーの網羅的解析

魚谷弘二, 藤原智洋, 吉田晶, 森田卓也, 武田健, 国定俊之, 吉岡祐亮, 植田幸嗣, 落谷孝広, 尾崎敏文

日本癌学会総会記事 74回 P - 1356 2015年10月

骨肉腫に対するドキソルビシンとp53発現腫瘍融解アデノウイルス製剤の併用療法

杉生和久, 田澤大, 長谷井嬢, 尾崎修平, 山川泰明, 大森敏規, 小松原将, 魚谷弘二, 藤原智洋, 国定俊之, 浦田泰生, 尾崎敏文, 藤原俊義

日本癌学会総会記事 74回 P - 1382 2015年10月

滑膜肉腫患者における分泌型microRNAの特定と新規バイオマーカーとしての実験的検証

吉田晶, 藤原智洋, 魚谷弘二, 根津悠, 武田健, 国定俊之, 川井章, 落谷孝広, 尾崎敏文

日本癌学会総会記事 74回 P - 3280 2015年10月

骨軟部肉腫細胞に対する腫瘍融解ウイルスの放射線増感作用

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 佐々木剛, 杉生和久, 魚谷弘二, 藤原智洋, 国定俊之, 浦田泰生, 尾崎敏文, 藤原俊義

日本癌学会総会記事 74回 E - 1276 2015年10月

Final results of a randomized phase II study comparing trabectedin and best supportive care (BSC) in patients (pts) with translocation-related sarcomas (TRS)

T. Kunisada, S. Takahashi, N. Araki, H. Sugiura, T. Ueda, T. Yonemoto, M. Takahashi, H. Morioka, H. Hiraga, T. Hiruma, A. Matsumine, A. Kawai

EUROPEAN JOURNAL OF CANCER 51 S704 - S704 2015年9月

小松原将, 山川泰明, 大森敏規, 杉生和久, 魚谷弘二, 吉田晶, 藤原智洋, 武田健, 国定俊之, 浦田泰生, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1795 - S1795 2015年9月

骨・軟部肉腫に対する腫瘍融解アデノウイルスと放射線療法の併用効果

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 杉生和久, 藤原智洋, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1673 - S1673 2015年9月

腫瘍融解アデノウイルスの骨・軟部腫瘍臨床組織検体に対する感染効率および適応症例の検討

吉田晶, 藤原智洋, 魚谷弘二, 長谷井嬢, 山川泰明, 大森敏規, 杉生和久, 武田健, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1673 - S1673 2015年9月

指神経に発生した巨指症を伴わないFibrolipomatous hamartomaの1例

清野正普, 武田健, 藤原智洋, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 秋季学会 ) 283 - 283 2015年9月

滑膜肉腫患者血清から特定した滑膜肉腫特異的分泌型miRNAに関する検討

魚谷弘二, 藤原智洋, 吉田晶, 山川泰明, 大森敏規, 杉生和久, 武田健, 国定俊之, 根津悠, 川井章, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1478 - S1478 2015年9月

骨盤発生の放射線照射後肉腫の治療成績

武田健, 国定俊之, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 秋季学会 ) 286 - 286 2015年9月

骨肉腫に対するテロメラーゼ依存性腫瘍融解アデノウイルスと骨周囲環境制御による新規治療戦略

山川泰明, 長谷井嬢, 田澤大, 杉生和久, 魚谷弘二, 大森敏規, 尾崎修平, 吉田晶, 藤原智洋, 武田健, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1798 - S1798 2015年9月

Liquid biopsyに応用可能なEwing肉腫細胞由来のexosome表面マーカーの同定

森田卓也, 藤原智洋, 魚谷弘二, 吉田晶, 山川泰明, 大森敏規, 杉生和久, 武田健, 国定俊之, 吉岡祐亮, 植田幸嗣, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1796 - S1796 2015年9月

骨軟部骨軟部腫瘍治療の新たな展開仙骨脊索腫治療後の再発切除術と重粒子線治療

国定俊之, 武田健, 藤原智洋, 鎌田正, 今井礼子, 不破信和, 尾崎敏文

日本癌治療学会誌 50 ( 3 ) 2021 - 2021 2015年9月

骨肉腫に対する化学療法とp53発現腫瘍融解アデノウイルス治療の併用効果

杉生和久, 小松原将, 大森敏規, 山川泰明, 吉田晶, 藤原智洋, 武田健, 国定俊之, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 8 ) S1799 - S1799 2015年9月

骨・軟部肉腫のゲノム解析と新治療開発の展望骨軟部腫瘍に対する手術療法の進歩

尾崎敏文, 国定俊之, 武田健, 藤原智洋

日本癌治療学会誌 50 ( 3 ) 2115 - 2115 2015年9月

Preclinical evaluation of radiotherapy in combination with radio-sensitizing telomerase-specific oncolytic virus for human bone and soft tissue sarcomas

Toshinori Omori, Yasuaki Yamakawa, Joe Hasei, Hiroshi Tazawa, Shuhei Osaki, Tusyoshi Sasaki, Kazuhisa Sugiu, Tomohiro Fujiwara, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 75 2015年8月

Both a visual and a semiquantitative analysis for differentiating benign from malignant chondrogenic bone tumors using Tc-99m (V) DMSA scintigraphy: a prospective study 査読

Takayoshi Shinya, Shuhei Sato, Toshiyuki Kunisada, Ryota Inai, Hiroyuki Yanai, Toshifumi Ozaki, Susumu Kanazawa

NUCLEAR MEDICINE COMMUNICATIONS 36 ( 8 ) 802 - 807 2015年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

ObjectiveThe aims of this prospective study were to assess the relationship between tumor aggressiveness and Tc-99m (V) dimercaptosuccinic acid (DMSA) uptake in chondrogenic bone tumors and the value of Tc-99m (V) DMSA scintigraphy for differentiating benign from malignant tumors.MethodsTwenty-four patients with chondrogenic tumors (19 benign and five malignant) underwent Tc-99m DMSA (V) scintigraphy. Radiopharmaceutical uptake was classified using a three-point scale to allow a visual-only analysis, and a tumor-to-background contrast (TBC) was computed using regions of interest to provide a semiquantitative analysis. Spearman's correlation coefficient was used to assess the correlation between tumor aggressiveness and TBC. The difference in TBC between benign and malignant tumors was analyzed with the Mann-Whitney U-test. An appropriate cutoff value of TBC was chosen for the diagnosis of malignancy of a tumor using receiver operating characteristic analysis.ResultsSix benign tumors showed negative uptake (uptake score 0), whereas 13 benign tumors showed positive uptake (n=10 uptake score 1; n=3 uptake score 2). All chondrosarcomas showed positive uptake (n=2 uptake score 1; n=3 uptake score 2). A significant correlation was found between tumor aggressiveness and TBC. A significant difference was seen in TBC between benign and malignant tumors. With the chosen cutoff value of TBC equal to 0.611, the sensitivity was 80.0%, specificity was 78.9%, the positive predictive value was 50.0%, and the negative predictive value was 93.8%.ConclusionTc-99m (V) DMSA scintigraphy may have the potential to improve diagnostic methods for detecting chondrosarcomas using visual and/or semiquantitative analyses.

DOI： 10.1097/MNM.0000000000000328

マウス骨肉腫におけるmyeloid derived suppressor cellsとmetforminの作用

Venous Thromboembolism after Total Hip Arthroplasty Diagnosed by Enhanced Computed Tomography: Comparison of Selective Thromboprophylaxis and No Thromboprophylaxis 査読

Yoshiki Okada, Hirosuke Endo, Shigeru Mitani, Kazuo Fujiwara, Tomonori Tetsunaga, Yohei Kagawa, Yosuke Fujii, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 69 ( 4 ) 205 - 212 2015年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Total hip arthroplasty (THA) is the most effective treatment for advanced or end-stage hip osteoarthritis. However, venous thromboembolism (VTE) remains one of its unresolved complications. We reviewed the records of 322 patients undergoing primary THA and investigated the efficacy of anticoagulant prophylaxis for VTE. Our study cohort consisted of 60 patients who received no anticoagulants, 100 patients who received a factor Xa inhibitor (fondaparinux), 100 patients who received low molecular weight heparin (enoxaparin), and 62 patients who selectively received no anticoagulant prophylaxis due to perioperative bleeding, weight, and/or hemoglobin concentration. Enhanced 64-slice multidetector row computed tomography was performed postoperatively for 7 days in all cases. The incidence of VTE in the four groups was 15%, 9.0%, 6.0%, and 6.4%, respectively. The incidence of VTE was significantly lower in the groups receiving anticoagulant prophylaxis and the group selectively receiving no anticoagulant prophylaxis than in the group receiving no anticoagulants. Complications of fondaparinux therapy included hepatic dysfunction in 4 cases (4.0%), minor bleeding in 2 cases (2.0%), persistent wound drainage in 3 cases (3.0%), and eruption in 1 case (1.0%). The complications of enoxaparin therapy were persistent wound drainage in 1 case (1.0%) and progression of anemia in 1 case (1.0%). The incidence of VTE was low in patients who selectively received no anticoagulant prophylaxis, so we conclude that anticoagulant prophylaxis should be used selectively in THA cases.

DOI： 10.18926/AMO/53556

藤原智洋, 国定俊之, 武田健, 山川泰明, 大森敏規, 上原健敬, 魚谷弘二, 杉生和久, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1308 - S1308 2015年6月

上原健敬, 榮川伸吾, 杉生和久, 魚谷弘二, 大森敏規, 山川泰明, 吉田晶, 藤原智洋, 武田健, 国定俊之, 鵜殿平一郎, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1238 - S1238 2015年6月

ナビゲーションシステムを用いた悪性骨・軟部腫瘍手術

国定俊之, 武田健, 藤原智洋, 杉本佳久, 荒瀧慎也, 瀧川朋亨, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1204 - S1204 2015年6月

前外側大腿皮弁で再建した踵骨骨肉腫の1例

小松原将, 武田健, 森田卓也, 杉生和久, 魚谷弘二, 藤原智洋, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1372 - S1372 2015年6月

骨・軟部肉腫に対する腫瘍融解アデノウイルスと放射線療法の併用効果

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 杉生和久, 藤原智洋, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1244 - S1244 2015年6月

小児の単発性骨嚢腫に合併した大腿骨近位部骨折に対する観血的治療

杉生和久, 藤原智洋, 武田健, 国定俊之, 野田知之, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1301 - S1301 2015年6月

ゾレドロン酸とテロメラーゼ依存性腫瘍融解アデノウイルスの併用療法は骨肉腫に対する抗腫瘍効果を増強し、骨破壊を抑制する

山川泰明, 長谷井嬢, 田澤大, 杉生和久, 魚谷弘二, 尾崎修平, 吉田晶, 藤原智洋, 武田健, 国定俊之, 浦田泰生, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1244 - S1244 2015年6月

悪性骨盤骨腫瘍術後リハビリテーション一時的創外固定法の有用性

国定俊之, 武田健, 藤原智洋, 野田知之, 堅山佳美, 千田益生, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1197 - S1197 2015年6月

滑膜肉腫における患者血清由来分泌型miRNAの特定

吉田晶, 藤原智洋, 魚谷弘二, 山川泰明, 大森敏規, 杉生和久, 武田健, 国定俊之, 根津悠, 川井章, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 89 ( 6 ) S1228 - S1228 2015年6月

Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study 査読

Akira Kawai, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Takanori Tanase, Tadashi Hasegawa, Shunji Takahashi

LANCET ONCOLOGY 16 ( 4 ) 406 - 416 2015年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Background Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma.
Methods We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1: 1) by the minimisation method to receive either trabectedin (1.2 mg/m(2) given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850.
Findings Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n= 39) or best supportive care (n= 37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5.6 months (95% CI 4.1-7.5) and the best supportive care group was 0.9 months (0.7-1.0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0.07 (90% CI 0.03-0.14 and 95% CI 0.03-0.16) by a Cox proportional hazards model (p< 0.0001). The most common drug-related adverse events for patients treated with trabectedin were nausea (32 [89%] of 36), decreased appetite (21 [58%]), decreased neutrophil count (30 [83%]), increased alanine aminotransferase (24 [67%]), and decreased white blood cell count (20 [56%]).
Interpretation Trabectedin significantly reduced the risk of disease progression and death in patients with advanced translocation-related sarcoma after standard chemotherapy such as doxorubicin, and should be considered as a new therapeutic treatment option for this patient population.

DOI： 10.1016/S1470-2045(15)70098-7

藤原智洋, 武田健, 国定俊之, 尾崎敏文

中国・四国整形外科学会雑誌 27 ( 1 ) 224 - 224 2015年4月

【骨腫瘍の診断と治療】化学療法 Ewing肉腫に対する化学療法

武田健, 藤原智洋, 国定俊之, 尾崎敏文

関節外科 34 ( 4 ) 338 - 343 2015年4月

骨軟部腫瘍における画像評価最前線シンチグラフィを用いた骨軟部腫瘍の機能的画像診断

国定俊之, 武田健, 藤原智洋, 上原健敬, 大森敏規, 尾崎敏文

臨床整形外科 50 ( 3 ) 229 - 235 2015年3月

記述言語：日本語出版者・発行元：(株)医学書院

骨軟部腫瘍の診断・治療では,骨シンチグラフィ,タリウムシンチグラフィが有用な画像診断法である.骨シンチグラフィは,骨腫瘍の活動性が評価可能であり,単発性・多発性発生の診断や悪性骨腫瘍では骨転移の診断に役立つ.タリウムシンチグラフィは腫瘍の活動性や悪性度を反映するため,術前治療の効果判定や良性・悪性の鑑別診断に有用である.術前治療が有効と判定可能であれば,縮小手術が可能となりうる.タリウムシンチグラフィとDMSAシンチグラフィを行うことで,軟骨系骨腫瘍の悪性度診断も可能とある.画像診断で良性・悪性の鑑別ができれば,外来診療での治療方針決定の一つの指標となる.(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J01554&link_issn=&doc_id=20150304050011&doc_link_id=10.11477%2Fmf.1408200144&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1408200144&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

骨温存のため液体窒素処理骨と腫瘍用人工関節術を併用した2例

上原健敬, 国定俊之, 大森敏規, 藤原智洋, 武田健, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 224 - 224 2015年3月

患肢温存術を行った15歳以下小児悪性骨腫瘍の治療成績

武田健, 国定俊之, 魚谷弘二, 杉生和久, 上原健敬, 大森敏規, 藤原智洋, 尾崎敏文

日本整形外科学会雑誌 89 ( 3 ) S687 - S687 2015年3月

原発性悪性骨・軟部腫瘍に対するpolypropylene meshを用いた腫瘍用人工関節置換術の治療成績

藤原智洋, 国定俊之, 武田健, 山川泰明, 上原健敬, 大森敏規, 魚谷弘二, 杉生和久, 尾崎敏文

日本整形外科学会雑誌 89 ( 3 ) S682 - S682 2015年3月

日本発新規microRNA阻害核酸製剤Synthetic Tough Decoyを用いた骨肉腫に対する前臨床的検討

藤原智洋, 根津悠, 吉田晶, 魚谷弘二, 武田健, 国定俊之, 伊庭英夫, 伊藤博, 尾崎敏文, 落合孝広, 川井章

日本整形外科学会雑誌 89 ( 3 ) S853 - S853 2015年3月

テロメラーゼ依存型腫瘍融解ウイルス治療とゾレドロネート併用療法の骨肉腫に対する前臨床的検討

山川泰明, 長谷井嬢, 藤原智洋, 武田健, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 175 - 175 2015年3月

水道水による手術時手洗いは骨軟部腫瘍切除後感染に影響するか

武田健, 国定俊之, 魚谷弘二, 杉生和久, 藤原智洋, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 110 - 110 2015年3月

自然退縮を認めた骨軟骨腫の2例

大森敏規, 藤原智洋, 武田健, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 216 - 216 2015年3月

小児に生じた単発性骨嚢腫による大腿骨近位部骨折に対する観血的治療経験

杉生和久, 武田健, 藤原智洋, 国定俊之, 野田知之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 179 - 179 2015年3月

【整形外科領域における集学的診療体制の構築】整形外科腫瘍領域(肉腫)における集学的治療

国定俊之, 武田健, 藤原智洋, 魚谷弘二, 杉生和久, 尾崎敏文

整形・災害外科 58 ( 3 ) 303 - 313 2015年3月

骨・軟部肉腫に対する腫瘍融解アデノウイルスと放射線療法の併用効果

大森敏規, 山川泰明, 長谷井嬢, 田澤大, 尾崎修平, 杉生和久, 藤原智洋, 国定俊之, 浦田泰夫, 藤原俊義

日本整形外科学会雑誌 89 ( 2 ) S142 - S142 2015年3月

骨肉腫患者における血中circulating miRNAの特定と臨床経過との相関

藤原智洋, 根津悠, 吉田晶, 魚谷弘二, 杉生和久, 大森敏規, 山川泰明, 武田健, 国定俊之, 川井章, 尾崎敏文

日本整形外科学会雑誌 89 ( 2 ) S139 - S139 2015年3月

骨盤腫瘍の外科的治療戦略骨盤腫瘍の治療方針

国定俊之, 武田健, 藤原智洋, 杉原進介, 尾崎敏文

日本整形外科学会雑誌 89 ( 2 ) S355 - S355 2015年3月

手術治療単独で悪性転化をきたした二次性悪性骨巨細胞腫の2例

藤原智洋, 国定俊之, 武田健, 魚谷弘二, 杉生和久, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 221 - 221 2015年3月

O-armによる術中CT撮影とナビゲーションシステムを用いて手術を行った類骨骨腫の1例

魚谷弘二, 武田健, 藤原智洋, 山川泰明, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 217 - 217 2015年3月

四肢長管骨骨欠損に対し処理骨を用いた生物学的再建

国定俊之, 武田健, 藤原智洋, 魚谷弘二, 杉原進介, 尾崎敏文

日本整形外科学会雑誌 89 ( 3 ) S684 - S684 2015年3月

有痛性dorsal defect of the patellaの一例

三宅孝昌, 藤原智洋, 武田健, 山川泰明, 国定俊之, 尾崎敏文

中部日本整形外科災害外科学会雑誌 58 ( 春季学会 ) 301 - 301 2015年3月

Erratum. Venous Thromboembolism after Total Hip Arthroplasty Diagnosed by Enhanced Computed Tomography:Comparison of Selective Thromboprophylaxis and No Thromboprophylaxis. 査読

Okada Y, Endo H, Tanaka T, Mitani S, Fujiwara K, Tetsunaga T, Kagawa Y, Fujii Y, Kunisada T, Ozaki T

Acta medica Okayama 69 ( 5 ) 325 - 325 2015年

microRNAs and Soft Tissue Sarcomas 査読

Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Toshifumi Ozaki

MICRORNA: CANCER: FROM MOLECULAR BIOLOGY TO CLINICAL PRACTICE 889 179 - 199 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER-VERLAG BERLIN

Soft tissue sarcomas are a highly heterogenous group of malignant tumors that originate from mesenchymal tissues including muscle, adipose and fibrous tissues, blood vessels, and peripheral nerves. A large variety of histological subtypes that current diagnostic approaches recognize present a diagnostic challenge because their clinical and histopathological characteristics are not always distinct. One of the important clinical problems is a lack of useful biomarkers; therefore, the discovery of biomarkers that can be used to detect tumors or predict tumor response to chemotherapy or radiotherapy could help clinicians provide more effective clinical management. Recent reports on microRNAs (miRNAs) in soft tissue sarcomas have provided clues to solve the problem. Evidence for miRNAs in tumor tissues as well as circulating miRNAs in patients' blood is accelerating the potential to transform clinical applications. In this chapter, we summarize the emerging evidence of dysregulated miRNAs in tumor tissues and patients' blood and discuss the potential of miRNAs as novel biomarkers and therapeutic targets.

DOI： 10.1007/978-3-319-23730-5_10

Immunotherapy for Bone and Soft Tissue Sarcomas 査読

Takenori Uehara, Tomohiro Fujiwara, Ken Takeda, Toshiyuki Kunisada, Toshifumi Ozaki, Heiichiro Udono

BIOMED RESEARCH INTERNATIONAL 2015 820813 2015年

記述言語：英語出版者・発行元：HINDAWI PUBLISHING CORPORATION

Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

DOI： 10.1155/2015/820813

Dorsal defect of the patellaの1例

Combination therapy of telomerase-specific oncolytic adenovirus and zoledronic acid in human osteosarcoma cells

Yasuaki Yamakawa, Joe Hasei, Hiroshi Tazawa, Toshinori Omori, Shuhei Osaki, Tsuyoshi Sasaki, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 74 ( 19 ) 2014年10月

Telomerase-dependent oncolytic adenovirus sensitizes human osteosarcoma cells to chemotherapy through Mcl-1 downregulation

Shuhei Osaki, Toshinori Omori, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Tsuyoshi Sasaki, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 74 ( 19 ) 2014年10月

藤原智洋, 国定俊之, 武田健, 尾崎敏文

関節外科 33 ( 10月増刊 ) 184 - 203 2014年10月

三宅孝昌, 藤原智洋, 武田健, 国定俊之, 尾崎敏文

中国・四国整形外科学会雑誌 26 ( 3 ) 460 - 460 2014年10月

小児に生じた単発性骨嚢腫による大腿骨近位部病的骨折

杉生和久, 武田健, 藤原智洋, 国定俊之, 尾崎敏文

中国・四国整形外科学会雑誌 26 ( 3 ) 460 - 460 2014年10月

Long-term follow-up of resection-replantation for sarcoma in the distal radius 査読

Eiji Nakada, Shinsuke Sugihara, Toshiyuki Kunisada, Toshifumi Ozaki

JOURNAL OF ORTHOPAEDIC SCIENCE 19 ( 5 ) 832 - 837 2014年9月

仙骨発生骨巨細胞腫の治療成績

藤原智洋, 国定俊之, 武田健, 尾崎敏文

中部日本整形外科災害外科学会雑誌 57 ( 秋季学会 ) 248 - 248 2014年9月

切除縁評価法の問題点切除縁評価法の問題点悪性骨腫瘍

国定俊之, 武田健, 藤原智洋, 柳井広之, 尾崎敏文

日本整形外科学会雑誌 88 ( 9 ) 588 - 594 2014年9月

記述言語：日本語出版者・発行元：(公社)日本整形外科学会

2005年〜2011年に治療した初診時遠隔転移を認めない高悪性骨腫瘍52例を対象に、最近の症例について検討し、悪性骨腫瘍の切除縁評価法に関する疑問点・問題点について検討した。組織型は骨肉腫34例、軟骨肉腫12例、Ewing肉腫3例等であった。52例の切除縁評価は2cm wide margin以上45例、1cm wide margin 4例、marginal margin以下3例であった。1cm wide marginとなった4例は血管温存目的(2例)および術前化学療法効果著効例での関節温存目的(2例)であった。marginal margin以下となった3例は骨盤発生、脊椎発生、大腿骨巨大腫瘍で、広範囲切除縁確保が困難であった。再発は4例に認め、2cm wide margin以上1例、marginal margin以下3例であった。最初の問題点は反応層の定義で、反応層をもう少し詳細に分類する必要がある。2番目の問題点は術前画像での切除縁設定の基準を決めることで、全国で統一した安全な切除縁設定の基準を決める必要があると思われた。

その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01133&link_issn=&doc_id=20141006030026&doc_link_id=%2Ffj2ortho%2F2014%2Fs08809%2F005%2F0588-0594%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffj2ortho%2F2014%2Fs08809%2F005%2F0588-0594%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

マウス骨肉腫・軟骨肉腫における免疫抑制細胞MDSCに対するmetforminの作用

上原健敬, 榮川伸吾, 大森敏規, 山川泰明, 武田健, 国定俊之, 尾崎敏文, 鵜殿平一郎

日本整形外科学会雑誌 88 ( 8 ) S1739 - S1739 2014年8月

Ribophorin II(RPN2)は骨肉腫の化学療法感受性および浸潤能を制御する

藤原智洋, 根津悠, 国定俊之, 武田健, 魚谷弘二, 杉生和久, 川井章, 落谷孝広, 尾崎敏文

日本整形外科学会雑誌 88 ( 8 ) S1362 - S1362 2014年8月

骨転移におけるゾレドロン酸と腫瘍融解アデノウイルスの併用治療

山川泰明, 長谷井嬢, 杉生和久, 大森敏規, 尾崎修平, 吉田晶, 藤原智洋, 国定俊之, 浦田泰生, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 88 ( 8 ) S1684 - S1684 2014年8月

腫瘍融解アデノウイルスと放射線療法を併用した骨・軟部肉腫に対する新規治療戦略

大森敏規, 長谷井嬢, 杉生和久, 山川泰明, 尾崎修平, 藤原智洋, 武田健, 吉田晶, 国定俊之, 田澤大, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 88 ( 8 ) S1362 - S1362 2014年8月

上腕骨近位部発生の悪性骨腫瘍に対する患肢温存術の治療成績

武田健, 国定俊之, 大森敏規, 上原健敬, 山川泰明, 尾崎修平, 長谷井嬢, 尾崎敏文

日本整形外科学会雑誌 88 ( 6 ) S1134 - S1134 2014年6月

骨盤Ewing肉腫に対して創外固定術を併用し腓骨移植術(non-vascularized)で再建した1例

大森敏規, 武田健, 上原健敬, 山川泰明, 長谷井嬢, 吉田晶, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 88 ( 6 ) S1294 - S1294 2014年6月

骨・軟部腫瘍切除術時のstaple使用は創合併症に影響しない

国定俊之, 上原健敬, 武田健, 長谷井嬢, 山川泰明, 井上円加, 尾崎敏文

日本整形外科学会雑誌 88 ( 6 ) S1242 - S1242 2014年6月

神経線維腫症1型に合併した巨大血腫に対して動脈塞栓術による止血を行った2例

武田健, 篠原健介, 長谷井嬢, 平木隆夫, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 88 ( 6 ) S1252 - S1252 2014年6月

骨肉腫におけるribophorin II(RPN2)の機能解析

藤原智洋, 根津悠, 川井章, 武田健, 国定俊之, 尾崎敏文, 落谷孝広

日本整形外科学会雑誌 88 ( 6 ) S1172 - S1172 2014年6月

がん治療の個別化における形成外科の役割、期待と現状骨軟部悪性腫瘍の治療診断・切除・再建

尾崎敏文, 国定俊之, 武田健, 藤原智洋, 長谷川健二郎, 木股敬裕

日本癌治療学会誌 49 ( 3 ) 678 - 678 2014年6月

A randomized phase II study comparing trabectedin (T) and best supportive care (BSC) in patients (pts) with translocation-related sarcomas (TRS). 査読

Shunji Takahashi, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Mitsuru Takahashi, Hideo Morioka, Tsukasa Yonemoto, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Akira Kawai

JOURNAL OF CLINICAL ONCOLOGY 32 ( 15 ) 2014年5月

Clinical outcomes of Kyocera Modular Limb Salvage system after resection of bone sarcoma of the distal part of the femur: the Japanese Musculoskeletal Oncology Group study 査読

Tomoki Nakamura, Akihiko Matsumine, Atsumasa Uchida, Akira Kawai, Yoshihiro Nishida, Toshiyuki Kunisada, Nobuhito Araki, Hideshi Sugiura, Masato Tomita, Masahiro Yokouchi, Takafumi Ueda, Akihiro Sudo

INTERNATIONAL ORTHOPAEDICS 38 ( 4 ) 825 - 830 2014年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

The Japanese Musculoskeletal Oncology Group have developed an original prosthesis called the Kyocera Modular Limb Salvage system (KMLS system). This prosthesis has a semi-rotating hinge joint and is particularly designed for people with an Asian body type. The metallic parts of the prosthesis are made entirely of titanium alloy. The purpose of this study is to evaluate the clinical outcomes of treatment using this system following tumour resection of primary bone sarcoma of the distal femur.
Between 2002 and 2010, 82 patients with primary bone sarcomas of the distal femur were treated. Seventeen patients underwent stem cementation, while 65 patients were treated with cementless prostheses. The mean follow-up period after surgery was 61 months.
Complications were observed in 28 of the 82 patients. Forty-one complications occurred in these 28 patients. Thirteen prostheses (16 %) required revision surgery due to complications, including five cases of stem breakage, three deep infections, three cases of aseptic loosening, one case of displacement of the shaft cap and one case of breakage of the tibial tray. The five-year overall prosthetic survival rate was 80.0 %. Four of the 82 patients underwent subsequent amputation due to local recurrence. The five-year limb salvage rate was 94.5 %. The mean function score according to the scoring system of the Musculoskeletal Tumour Society was 21.8 points (72.5 %).
Although further follow-up is required to determine the performance, this prosthesis is considered to be satisfactory for reconstruction of the distal femur after resection of bone sarcoma.

DOI： 10.1007/s00264-013-2151-7

武田健, 国定俊之, 長谷井嬢, 上原健敬, 大森敏規, 尾崎敏文

日本整形外科学会雑誌 88 ( 2 ) S131 - S131 2014年3月

Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study 査読

Y. Yoneda, T. Kunisada, N. Naka, Y. Nishida, A. Kawai, T. Morii, K. Takeda, J. Hasei, Y. Yamakawa, T. Ozaki

EJSO 40 ( 1 ) 49 - 54 2014年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

Background: The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection.
Methods: A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors.
Results: Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors.
Conclusions: Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients. (C) 2013 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2013.09.004

輸血不能のエホバの証人に対する人工股関節置換術の経験

田中孝明, 岡田芳樹, 尾﨑敏文, 藤原一夫, 遠藤裕介, 西田圭一郎

中国・四国整形外科学会雑誌 26 ( 2 ) 255 - 259 2014年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

Jehovah's Witnesses refuse blood transfusions on the basis of their religious belief. We report our experience with total hip arthroplasty without blood transfusion in a Jehovah's Witness. The patient was a 70-year-old woman who had been receiving treatment for rheumatoid arthritis for 34 year and had been taking anti-platelet agents for atrial fibrillation and hypertension. Plain radiographs revealed severe erosions (Larsen Grade 4) in the right hip. We used a cemented femoral component and reamed the acetabulum gently to minimize any bleeding, while performing intraoperative blood-salvaging autotransfusion. We carried out hybrid total hip arthroplasty with a cementless acetabular component and a cemented femoral component. The operation time was 62 minutes, intraoperative blood loss was 50ml, and postoperative blood loss was 90ml. The preoperative hemoglobin level was 9.9g/dl, and the lowest hemoglobin level was 6.8g/dl after surgery. At the final follow-up, the patient was able to walk with a T-shaped walking stick, and her Japanese Orthopaedics Association score (right/left) was 80 points/81 points on. We considered that the use of a cemented femoral component and gentle reaming of the acetabulum were factors that reduced bleeding during total hip arthroplasty.

DOI： 10.11360/jcsoa.26.255

MicroRNAs in Soft Tissue Sarcomas: Overview of the Accumulating Evidence and Importance as Novel Biomarkers 査読

Tomohiro Fujiwara, Toshiyuki Kunisada, Ken Takeda, Koji Uotani, Aki Yoshida, Takahiro Ochiya, Toshifumi Ozaki

BIOMED RESEARCH INTERNATIONAL 2014 592868 2014年

記述言語：英語出版者・発行元：HINDAWI PUBLISHING CORPORATION

Sarcomas are distinctly heterogeneous tumors and a variety of subtypes have been described. Although several diagnostic explorations in the past three decades, such as identification of chromosomal translocation, have greatly improved the diagnosis of soft tissue sarcomas, the unsolved issues, including the limited useful biomarkers, remain. Emerging reports on miRNAs in soft tissue sarcomas have provided clues to solving these problems. Evidence of circulating miRNAs in patients with soft tissue sarcomas and healthy individuals has been accumulated and is accelerating their potential to develop into clinical applications. Moreover, miRNAs that function as novel prognostic factors have been identified, thereby facilitating their use in miRNA-targeted therapy. In this review, we provide an overview of the current knowledge on miRNA deregulation in soft tissue sarcomas, and discuss their potential as novel biomarkers and therapeutics.

DOI： 10.1155/2014/592868

Truncated SSX Protein Suppresses Synovial Sarcoma Cell Proliferation by Inhibiting the Localization of SS18-SSX Fusion Protein 査読

Yasushi Yoneda, Sachio Ito, Toshiyuki Kunisada, Yuki Morimoto, Hirotaka Kanzaki, Aki Yoshida, Kenji Shimizu, Toshifumi Ozaki, Mamoru Ouchida

PLOS ONE 8 ( 10 ) e77564 2013年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PUBLIC LIBRARY SCIENCE

Synovial sarcoma is a relatively rare high-grade soft tissue sarcoma that often develops in the limbs of young people and induces the lung and the lymph node metastasis resulting in poor prognosis. In patients with synovial sarcoma, specific chromosomal translocation of t(X; 18) (p11.2; q11.2) is observed, and SS18-SSX fusion protein expressed by this translocation is reported to be associated with pathogenesis. However, role of the fusion protein in the pathogenesis of synovial sarcoma has not yet been completely clarified. In this study, we focused on the localization patterns of SS18-SSX fusion protein. We constructed expression plasmids coding for the full length SS18-SSX, the truncated SS18 moiety (tSS18) and the truncated SSX moiety (tSSX) of SS18-SSX, tagged with fluorescent proteins. These plasmids were transfected in synovial sarcoma SYO-1 cells and we observed the expression of these proteins using a fluorescence microscope. The SS18-SSX fusion protein showed a characteristic speckle pattern in the nucleus. However, when SS18-SSX was co-expressed with tSSX, localization of SS18-SSX changed from speckle patterns to the diffused pattern similar to the localization pattern of tSSX and SSX. Furthermore, cell proliferation and colony formation of synovial sarcoma SYO-1 and YaFuSS cells were suppressed by exogenous tSSX expression. Our results suggest that the characteristic speckle localization pattern of SS18-SSX is strongly involved in the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein. These findings could be applied to further understand the pathogenic mechanisms, and towards the development of molecular targeting approach for synovial sarcoma.

DOI： 10.1371/journal.pone.0077564

埋込型中心静脈カテーテルの断裂を来した2例

上原健敬, 武田健, 兒島聡一, 長谷井嬢, 郷原英夫, 国定俊之, 尾崎敏文

中国・四国整形外科学会雑誌 25 ( 3 ) 509 - 509 2013年10月

骨線維性異形成の治療成績

武田健, 国定俊之, 上原健敬, 大森敏規, 長谷井嬢, 尾崎敏文

中部日本整形外科災害外科学会雑誌 56 ( 秋季学会 ) 56 - 56 2013年9月

脛骨骨幹部骨折に合併した腓骨骨折固定の重要性

山川泰明, 野田知之, 上原健敬, 井上円加, 金澤智子, 中原龍一, 木浪陽, 島村安則, 国定俊之, 尾崎敏文

骨折 35 ( Suppl. ) S350 - S350 2013年6月

長期生存が得られた胸椎原発Ewing肉腫の2例

上原健敬, 国定俊之, 武田健, 長谷井嬢, 田中雅人, 尾崎敏文

日本整形外科学会雑誌 87 ( 6 ) S1170 - S1170 2013年6月

上腕三頭筋切除を要した軟部肉腫の術後患肢機能

武田健, 国定俊之, 長谷井嬢, 井上円加, 大森敏規, 上原健敬, 山川泰明, 尾崎修平, 吉田晶, 尾崎敏文

日本整形外科学会雑誌 87 ( 6 ) S1190 - S1190 2013年6月

Oncolytic adenovirus-armed p53 induces apoptosis significantly through upregulating miR-93 and 106b in human osteosarcoma cells

Joe Hasei, Tsuyoshi Sasaki, Hiroshi Tazawa, Yuuri Hashimoto, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 73 ( 8 ) 2013年4月

Management of Lumbar Artery Injury Related to Pedicle Screw Insertion 査読

Yoshihisa Sugimoto, Masato Tanaka, Hideo Gobara, Haruo Misawa, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 67 ( 2 ) 113 - 116 2013年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

We report on 2 patients who experienced injury to one of their lumbar arteries related to pedicle screw misplacement. In this report, the lumbar pedicle screw holes were made laterally with resultant injury to the lumbar artery. During surgery, arterial bleeding was controlled with pressure and gauze; however, the patients experienced vital shock after surgery. Vital shock ensued and they were rescued by catheter embolization. If patients receiving lumbar instrumentation surgery experience severe anemia or vital shock postoperatively, the surgeon should assume lumbar artery injury as a differential diagnosis.

DOI： 10.18926/AMO/49670

武田健, 上原健敬, 大森敏規, 原田遼三, 長谷井嬢, 吉田晶, 尾崎敏文, 国定俊之

中国・四国整形外科学会雑誌 25 ( 1 ) 239 - 239 2013年4月

Combined effect of zoledronic acid and telomerase-specific oncolytic virotherapy for human osteosarcoma cells.

Yasuaki Yamakawa, Joe Hasei, Hiroshi Tazawa, Shuhei Osaki, Tsuyoshi Sasaki, Toshiyuki Kunisada, Aki Yoshida, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 73 ( 8 ) 2013年4月

Dual Programmed Cell Death Pathways Induced by p53 Transactivation Overcome Resistance to Oncolytic Adenovirus in Human Osteosarcoma Cells 査読

Joe Hasei, Tsuyoshi Sasaki, Hiroshi Tazawa, Shuhei Osaki, Yasuaki Yamakawa, Toshiyuki Kunisada, Aki Yoshida, Yuuri Hashimoto, Teppei Onishi, Futoshi Uno, Shunsuke Kagawa, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

MOLECULAR CANCER THERAPEUTICS 12 ( 3 ) 314 - 325 2013年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC CANCER RESEARCH

Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301-resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301-resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301-sensitive (U2OS and HOS) and OBP-301-resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702-mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301-resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301-resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301-sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702-infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301-resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702-mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells. Mol Cancer Ther; 12(3); 314-25. (C)2012 AACR.

DOI： 10.1158/1535-7163.MCT-12-0869

A case of synovial sarcoma with brain metastasis treated with surgical resection and stereotactic radiosurgery 査読

Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Hiroyuki Yanai, Toshiyuki Kunisada, Toshifumi Ozaki, Isao Date

Neurological Surgery 41 ( 3 ) 255 - 262 2013年3月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Synovial sarcomas compromise between 5 to 10% of all soft tissue sarcomas in adults. Synovial sarcoma commonly occurs in the vicinity of the large joints and cranial metastasis is rare. Here, we describe a case with intracranial metastases of a synovial sarcoma A 41-year-old woman was admitted to our department with sensory aphasia. She had a history of a left inguinal synovial sarcoma and underwent surgery and chemotherapy for primary and metastatic lesions Head MRI revealed three gadolinium-enhancing lesions in the left frontal, parietal and parietotemporal lobe Gross total resection was achieved in the left parietotemporal lesion and pathological diagnosis was synovial sarcoma. Two weeks after surgery, she received cyber-knife radiosurgery and her neurological deficit was almost completely resolved Intracranial metastatic synovial sarcoma is rare. Surgical resection and stereotaxic radiosurgery was very effective in the present case.

若年性特発性関節炎による股関節強直に対し人工股関節全置換術を行った1例

原田遼三, 藤原一夫, 三澤治夫, 三宅由晃, 岡田芳樹, 尾﨑敏文, 遠藤裕介

中国・四国整形外科学会雑誌 25 ( 1 ) 13 - 17 2013年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

In patients with variable changes in pelvic inclination, total hip arthroplasty (THA) is required for accurate cup installation to prevent dislocation. Here we reported the use of THA for hip ankylosis due to juvenile idiopathic arthritis (JIA) and variable pelvic inclination with changes in posture. The patient was a 55-year-old woman, who had received medical treatment for JIA until the age of 14 year. She had been examined two years previously for bilateral leg pain and gait disturbance. Clinically, the lumbar spine had degenerative changes and the left hip joint was ankylosed at a 50-degree -flexed position, causing severe lordosis of the pelvis and lumbar spine and more severe lordosis during changes in posture. We treated the lumbar spine by laminectomy, and then THA was performed under a navigation system. Postoperatively, the patient was relieved of her symptoms and her ambulatory ability was improved. Anteversion of the pelvis with changes in posture remains, but the large femoral head has ensured that no dislocation has occurred up to the present. In cases of variable pelvic inclination due to changes in posture, use of a navigation system is useful intraoperatively for accurate cup installation, and a large femoral head matches any postoperative changes in pelvic inclination.

DOI： 10.11360/jcsoa.25.13

その他リンク： http://search.jamas.or.jp/link/ui/2013299772

A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus.

Sasaki T, Tazawa H, Hasei J, Osaki S, Kunisada T, Yoshida A, Hashimoto Y, Yano S, Yoshida R, Kagawa S, Uno F, Urata Y, Ozaki T, Fujiwara T

Gene Ther 2013年

外科的摘出および定位放射線治療が有用であった転移性滑膜肉腫の1例

大谷理浩, 市川智継, 黒住和彦, 柳井広之, 国定俊之, 尾崎敏文, 伊達勲

Neurological Surgery 41 ( 3 ) 255 - 262 2013年

Surgical Treatment for Congenital Kyphosis Correction Using Both Spinal Navigation and a 3-dimensional Model 査読

Yoshihisa Sugimoto, Masato Tanaka, Ryuichi Nakahara, Haruo Misawa, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 66 ( 6 ) 499 - 502 2012年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

An 11 year-old girl had 66 degrees of kyphosis in the thoracolumbar junction. For the purpose of planning for kyphosis correction, we created a 3-D, full-scale model of the spine and consulted spinal navigation. Three-dimensional models are generally used as tactile guides to verify the surgical approach and portray the anatomic relations specific to a given patient. We performed posterior fusion from Th10 to L3, and vertebral column resection of Th12 and L1. Screw entry points, directions, lengths and diameters were determined by reference to navigation. Both tools were useful in the bone resection. We could easily detect the posterior element to be resected using the 3D model. During the anterior bony resection, navigation helped us to check the disc level and anterior wall of the vertebrae, which were otherwise difficult to detect due to their depth in the surgical field. Thus, the combination of navigation and 3D models helped us to safely perform surgery for a patient with complex spinal deformity.

DOI： 10.18926/AMO/49047

クラウドを利用した遠隔カスタムメイドインプラント作成システム

井上円加, 中原龍一, 島村安則, 野田知之, 国定俊之, 尾崎敏文

骨折 34 ( 4 ) 959 - 963 2012年12月

記述言語：日本語出版者・発行元：(一社)日本骨折治療学会

【目的】当科では鎖骨骨幹部骨折に対し、CT画像を元にプレベンディングしたプレートを用いたMIPO法を行い、良好な結果を得ている。遠隔地の小規模施設でも同様の手術を行うため、クラウドサーバー経由でのCTの編集画像を転送し、作成したプレートを当該施設に輸送して手術を行うシステムを構築した。【方法】健側鎖骨のCT画像からプレベンディング用の画像データを作成する。手術を行う施設で画像処理を行い、クラウドサーバーに匿名化した編集画像を転送する。データを元に当院でプレートをプレベンディングし、当該施設に輸送し、手術を行った。【結果】当該施設でのデータ編集は30分で可能であった。編集後の画像データ量は大幅に削減でき、ネットワーク上での転送に支障はなかった。【結論】当科と手術を行う病院でクラウドサーバーを構築し、低コストでカスタムメイドインプラント作成ネットワークを作り、大学病院の手術方法を他院で実現できた。(著者抄録)

Tc-99m DMSA (V) scintigraphy for evaluation in patients with cartilaginous bone tumor

T. Shinya, S. Sato, A. Alafate, H. Gobara, K. Kato, T. Kunisada, T. Ozaki, S. Kanazawa

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 39 S473 - S474 2012年10月

MicroRNA-21 correlates with tumorigenesis in malignant peripheral nerve sheath tumor (MPNST) via programmed cell death protein 4 (PDCD4) 査読

Satoru Itani, Toshiyuki Kunisada, Yuki Morimoto, Aki Yoshida, Tsuyoshi Sasaki, Sachio Ito, Mamoru Ouchida, Shinsuke Sugihara, Kenji Shimizu, Toshifumi Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 138 ( 9 ) 1501 - 1509 2012年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

We investigated the miRNA profile in peripheral nerve tumors and clarified the involvement of miRNA in the development and progression of MPNST in comparison with neurofibroma (NF). In addition, we attempted to seek associations between the miRNA and their potential targets in MPNST.
Global miRNA expression profiling was investigated for clinical samples of 6 MPNSTs and 6 NFs. As detected by profiling analysis, the expressions of miR-21 in clinical samples of 12 MPNSTs, 11 NFs, and 5 normal nerves, and 3 MPNST cell lines were compared using quantitative real-time reverse transcription PCR. MPNST cell line (YST-1) was transfected with miR-21 inhibitor to study its effects on cell proliferation, caspase activity, and the expression of miR-21 targets.
Analysis of miRNA expression profiles in MPNST and NF revealed significantly altered expression levels of nine miRNAs, one of those, miR-21, and its putative target, programmed cell death protein 4 (PDCD4), were selected for further studies. miR-21 expression level in MPNST was significantly higher than that in NF (P < 0.05). In MPNST cells, transfection of miR-21 inhibitor significantly increased caspase activity (P < 0.01), significantly suppressed cell growth (P < 0.05), and upregulated protein level of PDCD4, indicating that miR-21 inhibitor could induce cell apoptosis of MPNST cells.
These results suggest that miR-21 plays an important role in MPNST tumorigenesis and progression through its target, PDCD4. MiR-21 and PDCD4 may be candidate novel therapeutic targets against the development or progression of MPNSTs.

DOI： 10.1007/s00432-012-1223-1

Segmental Pedicle Screw Fixation for a Scoliosis Patient with Post-laminectomy and Post-irradiation Thoracic Kyphoscoliosis of Spinal Astrocytoma 査読

Masato Tanaka, Yoshihiro Sugimoto, Haruo Misawa, Tomoyuki Takigawa, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 66 ( 4 ) 363 - 368 2012年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Spinal deformity is an important clinical manifestation after surgery for spinal cord tumors. One-third of patients who receive laminectomies and irradiation of the spinal column develop scoliosis, kyphosis, or kyphoscoliosis. Recent reports indicate good results after scoliosis surgery using segmental pedicle screws and a navigation system, but these reported studies have not included surgery for post-laminectomy kyphosis. Hooks and wires are ineffective in such patients who undergo laminectomy, and there are also high perioperative risks with insertion of pedicle screws because landmarks have been lost. Here, we report on the 5-year follow-up of a 13-year-old male patient with post-laminectomy and post-irradiation thoracic kyphoscoliosis after surgical treatment of spinal astrocytoma. Posterior segmental pedicle screw fixation was performed safely using a computer-assisted technique. The authors present the first case report for treatment of this condition using a navigation system.

DOI： 10.18926/AMO/48692

Statistical Analysis of Prognostic Factors for Survival in Patients with Spinal Metastasis 査読

Masaki Kataoka, Toshiyuki Kunisada, Masato Tanaka, Ken Takeda, Satoru Itani, Yoshihisa Sugimoto, Haruo Misawa, Masuo Senda, Shinnosuke Nakahara, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 66 ( 3 ) 213 - 219 2012年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

There are a variety of treatment options for patients with spinal metastasis, and predicting prognosis is essential for selecting the proper treatment. The purpose of the present study was to identify the significant prognostic factors for the survival of patients with spinal metastasis. We retrospectively reviewed 143 patients with spinal metastasis. The median age was 61 years. Eleven factors reported previously were analyzed using the Cox proportional hazards model: gender, age, performance status, neurological deficits, pain, type of primary tumor, metastasis to major organs, previous chemotherapy, disease-free interval before spinal metastasis, multiple spinal metastases, and extra-spinal bone metastasis. The average survival of study patients after the first visit to our clinic was 22 months. Multivariate survival analysis demonstrated that type of primary tumor (hazard ratio [HR] = 6.80, p < 0.001), metastasis to major organs (HR = 2.01, p = 0.005), disease-free interval before spinal metastasis (HR = 1.77, p = 0.028), and extra-spinal bone metastasis (HR = 1.75, p = 0.017) were significant prognostic factors. Type of primary tumor was the most powerful prognostic factor. Other prognostic factors may differ among the types of primary tumor and may also be closely associated with primary disease activity. Further analysis of factors predicting prognosis should be conducted with respect to each type of primary tumor to help accurately predict prognosis.

DOI： 10.18926/AMO/48560

後内側剪断骨片を有する脛骨近位部関節内骨折に対する固定方法の検討

小澤正嗣, 野田知之, 山川泰明, 金澤智子, 長谷井嬢, 齋藤太一, 中原龍一, 木浪陽, 島村安則, 国定俊之, 尾崎敏文

骨折 34 ( Suppl. ) S170 - S170 2012年6月

関節内骨折の克服治療成績の向上を目指して関節内骨折の克服治療成績の向上を目指して足関節内骨折

野田知之, 島村安則, 中原龍一, 齋藤太一, 金澤智子, 長谷井嬢, 井上円加, 山川泰明, 国定俊之, 尾崎敏文, 木浪陽

骨折 34 ( Suppl. ) S9 - S9 2012年6月

鎖骨骨幹部骨折に対するMIPO法による治療成績(第2報)

島村安則, 中原龍一, 斉藤太一, 金澤智子, 小澤正嗣, 井上円加, 山川泰明, 原田遼三, 中道亮, 島村好信, 国定俊之, 野田知之, 尾崎敏文

骨折 34 ( Suppl. ) S120 - S120 2012年6月

p53-mediated apoptotic signaling overcomes the resistance to oncolytic adenovirus in human osteosarcoma cells

Joe Hasel, Tsuyoshi Sasaki, Hiroshi Tazawa, Yuuri Hashimoto, Toshiyuki Kunisada, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 72 2012年4月

右下腿軟部に発生した組織球性悪性腫瘍の一例

森本裕樹, 井谷智, 尾﨑敏文, 国定俊之

中国・四国整形外科学会雑誌 24 ( 1 ) 5 - 9 2012年

記述言語：日本語出版者・発行元：The Chugoku-Shikoku Orthopaedic Association

Histiocytic sarcoma is a rare hematopoietic malignancy with a poor prognosis. We report a 31-year-old woman who developed histiocytic sarcoma in the lower extremity. An open biopsy was required because a definitive diagnosis could not be made on the basis of a core-needle biopsy specimen. The diagnosis of histiocytic sarcoma was established using immunohistochemistry. No metastatic lesion was detected by PET-CT, and wide resection based on the procedure for a malignant soft tissue tumor was performed without neo-adjuvant chemotherapy. However, adjuvant radiotherapy was performed because there are few reports of histiocytic sarcoma being treated using surgery alone. During 35 months of follow-up, neither local recurrence nor distant metastasis has been observed. Our experience suggests that if a solitary lesion of histiocytic sarcoma can be resected with a sufficient margin, chemotherapy may be unnecessary.

DOI： 10.11360/jcsoa.24.5

外傷による足部骨髄炎の 5 例

岡田芳樹, 野田知之, 西山武, 中原龍一, 島村安則, 尾﨑敏文

中国・四国整形外科学会雑誌 24 ( 2 ) 209 - 214 2012年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

Osteomyelitis after trauma or surgery can be problematic, especially pedal osteomyelitis including calcaneal osteomyelitis. Here we report the results and problems associated with surgery for pedal osteomyelitis in five patients (four men and one woman). The mean age of the patients was 37 years (range 12-51 years). Four developed infection after surgery and one after contusion. Treatment involved thorough debridement of the infected area and filling of the dead space with artificial bone or cement beads incorporating a DDS (Drug Delivery System). Until the infection had subsided, we repeated this operation every 3 to 4 weeks. Finally, we performed a subtalar arthrodesis in one patient, a desis of the cuneiform bone in one, and auto-bone graft in three. The bacteria detected were MSSA in two patients, MRSA in three patients (including one case of MRSA combined with fungus). All of the infections subsided within a mean period of 9.6 months (range 5-21 months). The mean operation time was 3.2 hours (range 1-5 hours). We used mainly a DDS that released antibiotics from cement or artificial bone. There was no complication associated with this treatment. Since the calcaneus has poor vascularization and a large proportion of cancellous bone, pedal osteomyelitis, especially in the calcaneus, is challenging to treat. Filling the dead space using a DDS is effective for control of infection.

DOI： 10.11360/jcsoa.24.209

その他リンク： http://search.jamas.or.jp/link/ui/2013107539

高悪性度腫瘍の脊椎転移に関する治療成績

馬﨑哲朗, 田中雅人, 杉本佳久, 瀧川朋亨, 鉄永倫子, 塩崎泰之, 尾﨑修平, 尾﨑敏文, 国定俊之, 三澤治夫, 片岡昌樹

中国・四国整形外科学会雑誌 24 ( 2 ) 273 - 277 2012年

記述言語：日本語出版者・発行元：中国・四国整形外科学会

We report the outcome of patients with metastatic spine tumors showing high-grade malignancy using the Tokuhashi scoring system. A retrospectively compared 21 patients with such tumors (group H) and 29 patients with spinal metastases showing low-grade malignancy (group L). There were 18 men and 3 women in group H, and 16 men and 13 women in group L, and the average patient ages were 55 years and 65 years, respectively. All of the patients were scored with the Tokuhashi scoring system and evaluated for neurological symptoms with the ASIA Impairment Scale (AIS). Results : The rates of improvement in the AIS score and gait ability were almost the same in both groups. Among patients who we were able to follow postoperatively for 6 months or more, 7 in group H and 4 in group L died within 6 months. The mean survival period was 12 months in group H and 17 months in group L. Conclusions : The outcome after treatment in group H was almost the same as that in group L. This may have been due to progress in the treatment of malignancy. Further studies to determine the indications for surgery in such patients are warranted.

DOI： 10.11360/jcsoa.24.273

その他リンク： http://search.jamas.or.jp/link/ui/2013107551

Thallium-201 Scintigraphy Is an Effective Diagnostic Modality to Distinguish Malignant From Benign Soft-Tissue Tumors 査読

Naoaki Kawakami, Toshiyuki Kunisada, Shuhei Sato, Yuki Morimoto, Masato Tanaka, Tsuyoshi Sasaki, Shinsuke Sugihara, Hiroyuki Yanai, Susumu Kanazawa, Toshifumi Ozaki

CLINICAL NUCLEAR MEDICINE 36 ( 11 ) 982 - 986 2011年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Background: The aim of this study is to evaluate whether thallium-201 (201-Tl) scintigraphy can differentiate malignant from benign soft-tissue tumors.
Methods: Between April 1995 and December 2005, 192 patients with soft-tissue tumors (85 malignant and 107 benign) underwent 201-Tl scintigraphy before treatment. Isotope uptake was used as a proxy for tumor-to-background ratio (TBR). The accuracy of TBR on early and delayed imaging was evaluated using the Mann-Whitney U and chi(2) tests.
Results: There was a statistically significant difference in mean TBR on early and delayed imaging of malignant and benign soft-tissue tumors (124% +/- 109% vs. 22% +/- 42%, and 82% +/- 83% vs. 12% +/- 25%, P < 0.0001). A TBR cutoff of 20% indicated the probability of malignancy on early and delayed imaging (82% sensitivity and 77% specificity; 82% sensitivity and 84% specificity, P < 0.0001). Well-differentiated liposarcomas showed low isotope accumulation, while pigmented villonodular synovitis and giant cell tumors of the tendon sheath showed high isotope accumulation.
Conclusions: Thallium-201 scintigraphy can distinguish malignant from benign tumors with relatively high accuracy. With the exception of low grade liposarcomas and locally aggressive benign tumors, 201-Tl scintigraphy may be an effective diagnostic modality to differentiate malignant from benign soft-tissue tumors.

DOI： 10.1097/RLU.0b013e3182177407

関節鏡視下切除を行った股関節色素性絨毛結節性滑膜炎の1例

武田健, 国定俊之, 遠藤裕介, 中道亮, 井谷智, 尾崎敏文

中国・四国整形外科学会雑誌 23 ( 3 ) 440 - 440 2011年10月

液体窒素処理骨による再建を行った肩甲骨Ewing肉腫の1例

金澤智子, 国定俊之, 島村安則, 野田知之, 斉藤太一, 尾崎敏文

肩関節 36 ( 1 ) 167 - 167 2011年9月

上腕骨通顆骨折に対する内固定法の力学的比較 ONI plate対従来固定法

島村安則, 今谷潤也, 野田知之, 中原龍一, 齋藤太一, 金澤智子, 井上円加, 小澤正嗣, 古松毅之, 国定俊之, 西田圭一郎, 橋詰博行, 尾崎敏文

日本整形外科学会雑誌 85 ( 8 ) S1338 - S1338 2011年8月

脛骨近位部関節内骨折の関節面骨折形態のCTによる評価

小澤正嗣, 野田知之, 金澤智子, 長谷井嬢, 齋藤太一, 中原龍一, 島村安則, 国定俊之, 尾崎敏文

骨折 33 ( Suppl. ) S212 - S212 2011年7月

鎖骨骨幹部骨折に対するMIPO法による治療成績

島村安則, 中原龍一, 斉藤太一, 金澤智子, 小澤正嗣, 井上円加, 国定俊之, 野田知之, 尾崎敏文, 島村好信

骨折 33 ( Suppl. ) S239 - S239 2011年7月

上腕骨近位端骨折に対する最少侵襲プレート骨接合術(MIPO)による手術成績

島村安則, 中原龍一, 斉藤太一, 金澤智子, 小澤正嗣, 井上円加, 国定俊之, 野田知之, 尾崎敏文, 島村好信

骨折 33 ( Suppl. ) S80 - S80 2011年7月

下腿骨幹部骨折術後非感染性偽関節の治療経験

藤原智洋, 野田知之, 金澤智子, 長谷井嬢, 中原龍一, 島村安則, 国定俊之, 尾崎敏文, 寺田忠司

骨折 33 ( Suppl. ) S245 - S245 2011年7月

Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas

Tsuyoshi Sasaki, Hiroshi Tazawa, Jo Hasei, Toshiyuki Kunisada, Aki Yoshida, Yuki Morimoto, Yasuo Urata, Kazuhiro Nouso, Toshifumi Ozaki, Toshiyoshi Fujiwara

CANCER RESEARCH 71 2011年4月

Preclinical Evaluation of Telomerase-Specific Oncolytic Virotherapy for Human Bone and Soft Tissue Sarcomas 査読

Tsuyoshi Sasaki, Hiroshi Tazawa, Jo Hasei, Toshiyuki Kunisada, Aki Yoshida, Yuuri Hashimoto, Shuya Yano, Ryosuke Yoshida, Futoshi Uno, Shunsuke Kagawa, Yuki Morimoto, Yasuo Urata, Toshifumi Ozaki, Toshiyoshi Fujiwara

CLINICAL CANCER RESEARCH 17 ( 7 ) 1828 - 1838 2011年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC CANCER RESEARCH

Purpose: Tumor-specific replication-selective oncolytic virotherapy is a promising antitumor therapy for induction of cell death in tumor cells but not of normal cells. We previously developed an oncolytic adenovirus, OBP-301, that kills human epithelial malignant cells in a telomerase-dependent manner. Recent evidence suggests that nonepithelial malignant cells, which have low telomerase activity, maintain telomere length through alternative lengthening of telomeres (ALT). However, it remains unclear whether OBP-301 is cytopathic for nonepithelial malignant cells. Here, we evaluated the antitumor effect of OBP-301 on human bone and soft tissue sarcoma cells.
Experimental Design: The cytopathic activity of OBP-301, coxsackie and adenovirus receptor (CAR) expression, and telomerase activity were examined in 10 bone (OST, U2OS, HOS, HuO9, MNNG/HOS, SaOS-2, NOS-2, NOS-10, NDCS-1, and OUMS-27) and in 4 soft tissue (CCS, NMS-2, SYO-1, and NMFH-1) sarcoma cell lines. OBP-301 antitumor effects were assessed using orthotopic tumor xenograft models. The fiber-modified OBP-301 (termed OBP-405) was used to confirm an antitumor effect on OBP-301-resistant sarcomas.
Results: OBP-301 was cytopathic for 12 sarcoma cell lines but not for the non-CAR-expressing OUMS27 and NMFH-1 cells. Sensitivity to OBP-301 was dependent on CAR expression and not on telomerase activity. ALT-type sarcomas were also sensitive to OBP-301 because of upregulation of human telomerase reverse transcriptase (hTERT) mRNA following virus infection. Intratumoral injection of OBP-301 significantly suppressed the growth of OST and SYO-1 tumors. Furthermore, fiber-modified OBP-405 showed antitumor effects on OBP-301-resistant OUMS-27 and NMFH-1 cells.
Conclusions: A telomerase-specific oncolytic adenovirus is a promising antitumor reagent for the treatment of bone and soft tissue sarcomas. Clin Cancer Res; 17(7); 1828-38. (C) 2011 AACR.

DOI： 10.1158/1078-0432.CCR-10-2066

当院にて経験したＷｅｌｌｌｅｇｃｏｍｐａｒｔｍｅｎｔｓｙｎｄｒｏｍｅの１例

軟部腫瘍の良悪性鑑別におけるTI-201腫瘍シンチグラフィの有用性

佐藤修平, 稲井良太, 原田聡介, 新家崇義, 郷原英夫, 奥村能啓, 国定俊之, 尾崎敏文, 金澤右

日本医学放射線学会学術集会抄録集 70回 S365 - S366 2011年2月

肩甲骨切除を伴った骨軟部肉腫2例の治療経験

岡田芳樹, 森本裕樹, 井谷智, 国定俊之, 尾﨑敏文

中部日本整形外科災害外科学会雑誌 54 ( 1 ) 41 - 42 2011年

岡田芳樹, 橋詰謙三, 中原龍一, 西田圭一郎, 野田知之, 尾﨑敏文

中部日本整形外科災害外科学会雑誌 54 ( 4 ) 869 - 870 2011年

Minimally invasive plate osteosynthesis for osteofibrous dysplasia of the tibia: a case report. 査読国際誌

Nakahara H, Kunisada T, Noda T, Ozaki T

Journal of orthopaedic surgery (Hong Kong) 18 ( 3 ) 374 - 377 2010年12月

ケルブールプレートと人工骨を併用した臼蓋再置換術THAの短期成績の検討

遠藤裕介, 三谷茂, 藤原一夫, 三宅由晃, 鉄永智紀, 国定俊之, 尾崎敏文

日本人工関節学会誌 40 102 - 103 2010年12月

記述言語：日本語出版者・発行元：(一社)日本人工関節学会

2000年〜2007年に人工骨とケルブールプレート併用の臼蓋側再置換術(THA)を施行した骨欠損症37例中2年以上経過観察できた30例30関節(男性5例、女性25例、44〜78歳・平均66歳)を対象に、短期成績について検討した。前回手術は人工骨頭置換術(BHA)2例、人工股関節置換術(THA)28例で前回手術からの経過観察期間は平均15年(2〜26年)、再置換の理由は無菌性のゆるみ27例、感染2例、脱臼1例、平均追跡期間は4年6ヵ月(2〜9年)であった。術前のAAOS分類はIが5股、IIが2股、IIIが20股、IVが3股であった。術直後のX線像におけるケルブールプレートのフックの設置位置は14股(46%)に外側設置を認め、荷重部の移植骨の厚みは平均15mm(0〜27mm)であった。最終調査時迄に遅発性感染を2例に認め、スクリューのゆるみ・破損を6股(20%)に認めた。カップの内方への移動を7股(23%)に認め移動距離は平均7.2mm(1〜20mm)であった。JOAスコアは術前平均50点から最終観察時平均77点と改善した。感染例2例を除く28股においてカップの移動を生じた5股と問題のなかった23股を比較検討したが両群に術前の平均年齢、BMIに差はなく成績不良群には術前AAOS分類でタイプIVが2股存在した。成績不良群は全例荷重部にブロックを使用せずに人工骨顆粒のみを使用していた。荷重部の移植骨の厚みには有意差は認めず、プレートの設置状態が良好であった15股中2股に成績不良を認めた。

当科における滑膜肉腫の治療成績

藤原智洋, 森本裕樹, 井谷智, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 84 ( 6 ) S998 - S998 2010年6月

Operative Treatment for Pincer Type Femoroacetabular Impingement: A Case Report 査読

Hirosuke Endo, Tomoyuki Noda, Shigeru Mitani, Ryuichi Nakahara, Tomonori Tetsunaga, Toshiyuki Kunisada, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 64 ( 2 ) 149 - 154 2010年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Femoroacetabular impingement (FAT) is a condition characterized by the impingement of the femur and acetabulum. In Japan, this disorder has become recognized gradually. Here we report a rare case of surgically treated FAT, associated with an osseous protrusion on the acetabulum of a 30-year-old female. Plain computed tomography (CT) and reconstructive 3D-CT images clearly demonstrated an anterolateral bony protrusion. Hip arthroscopy showed no degeneration of the cartilage on either the femoral or acetabular side, but degeneration at the edge of labrum was observed in the region of the bony protrusion. The complete removal of the bony protrusion under hip arthroscopy was thus considered impracticable, and a small skin incision was therefore made anteriorly to approach the acetabulum. The Short-Form 36-Item Health Survey (SF-36) revealed improvement in all scores.

DOI： 10.18926/AMO/32853

Frequent methylation of RASSF1A in synovial sarcoma and the anti-tumor effects of 5-aza-2'-deoxycytidine against synovial sarcoma cell lines 査読

Kunihiko Numoto, Aki Yoshida, Shinsuke Sugihara, Toshiyuki Kunisada, Yuki Morimoto, Yasushi Yoneda, Yasuko Fujita, Keiichiro Nishida, Mamoru Ouchida, Toshifumi Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 136 ( 1 ) 17 - 25 2010年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

In this study, the methylation status of RASSF1A in synovial sarcomas and the effect of de-methylation on synovial sarcoma were examined.
The methylation status in 74 soft tissue sarcomas (STSs) including 21 synovial sarcomas was determined by methylation specific PCR. The effect of the de-methylating agent 5-aza-2'-deoxycytidine (5-Aza-dC) on synovial sarcoma was examined using synovial sarcoma cell lines (SYO-1 and HS-SY-II).
RASSF1A methylation was observed in 10 (47.6%) of 21 synovial sarcomas and in 10 (18.9%) of 53 the other STSs (P = 0.0295). De-methylation of the cells by treatment with 5-Aza-dC induced re-expression of RASSF1A and growth suppression of the cells. The calculated IC50 of 5-Aza-dC against the SYO-1 and the HS-SY-II cells were 0.9 and 1.3 mu M (96 h), respectively. With twice weekly administration of 1 or 10 mg/kg 5-Aza-dC, the growth of the mouse xenograft tumors of SYO-1 was significantly suppressed in comparison to the controls (P < 0.01).
This is the first report showing the anti-tumor effect of 5-Aza-dC on synovial sarcoma. 5-Aza-dC is suggested to have a good therapeutic potential against synovial sarcoma.

DOI： 10.1007/s00432-009-0632-2

仙骨骨巨細胞腫に対する動脈塞栓術 : 腫瘍の縮小を認めた1症例

佐々木剛, 森本裕樹, 尾﨑敏文, 国定俊之, 郷原英夫

中国・四国整形外科学会雑誌 22 ( 2 ) 267 - 272 2010年

記述言語：日本語出版者・発行元：The Chugoku-Shikoku Orthopaedic Association

Giant cell tumor (GCT) of the sacrum is rare and difficult to treat, although several treatment modalities have been reported. Here we report a patient with sacral GCT who underwent selective intra-arterial embolization. The patient, a 23-year-old woman, had been treated with curettage alone at a local hospital. However, 4 months after surgery, MRI showed recurrence of the tumor, and the patient was referred to our hospital for further treatment. After discussion with her and her family, they accepted intra-arterial embolization of the tumor vessels. Embolization using a temporary embolic agent reduced the size of the tumor and the level of serum acid phosphatase (ACP). However, both the tumor size and the level of ACP increased a few months after the procedure. Therefore, embolization was performed using an embolic agent consisting of spherical particles. MRI showed a marked reduction of tumor size 1 month after the last embolization, and the level of serum ACP also fell to less than the standard value. Embolization using a spherical-particulate embolic agent can be an effective treatment for sacral GCT.

DOI： 10.11360/jcsoa.22.267

骨盤腫瘍に対する創外固定を併用したhip transposition法の治療経験

藤原智洋, 国定俊之, 井谷智, 森本裕樹, 佐々木剛, 尾﨑敏文

中部日本整形外科災害外科学会雑誌 53 ( 4 ) 937 - 938 2010年

自然退縮を認めた骨軟骨腫の2例

藤原智洋, 国定俊之, 井谷智, 森本裕樹, 尾崎敏文

岡山医学会雑誌 121 ( 3 ) 233 - 233 2009年12月

血管病変と診断され血管置換術が行われた滑膜肉腫の2例

藤原智洋, 国定俊之, 佐々木剛, 井谷智, 森本裕樹, 尾崎敏文

中部日本整形外科災害外科学会雑誌 52 ( 秋季学会 ) 214 - 214 2009年9月

末梢神経系腫瘍microRNA発現プロファイリングの検討

井谷智, 森本裕樹, 伊藤佐智夫, 大内田守, 吉田晶, 上甲良二, 米田泰史, 佐々木剛, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 83 ( 8 ) S1151 - S1151 2009年8月

Surgical Treatment of Metastatic Vertebral Tumors 査読

Masato Tanaka, Shinnosuke Nakahara, Yasuo Ito, Toshiyuki Kunisada, Haruo Misawa, Koichiro Koshimune, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 63 ( 3 ) 145 - 150 2009年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Surgical treatment of metastatic spinal cord compression is controversial. The purpose of this study was to investigate the effectiveness of our current surgical treatments and the use of spinal instrumentation. In this retrospective study covering the years between 1990 and 2006, 100 patients with spinal metastases which were secondary to various cancers underwent posterior and/or anterior decompression with spinal stabilization for the purposes of reduction of pain, and/or to help correct or improve neurological deficits. The group was made up of 60 men and 40 women whose ages ranged from 16 to 83 years (average of 60 years), and the average follow-up period was 14 months. The effect of treatment upon pain relief and neural deficits was assessed, and the cumulative survival rate was calculated by the Kaplan-Meier method. The average surgical time was 185 min. This was calculated based on the following times, listed here with the surgery type: 178 min for posterior surgery; 245 min for anterior surgery; 465 min for combined surgery; and 475 min for total en bloc spondylectomy. Average blood loss during surgery was 1,630 ml for posterior surgery, 1,760 ml for anterior surgery, 1,930 ml for combined surgery, and 3,640 ml for total en bloc spondylectomy. Preoperative pain and paralysis were improved by 88% and 53%, respectively. In regards to surgical complications, postoperative epidural hematoma was observed in 2 patients, and instrumentation-related infection was observed in 1. Only 2 patients died within 2 months of surgery. In conclusion, posterior and/or anterior decompression with spinal stabilization is a safe and effective treatment for patients with spinal metastases, and can improve their quality of life.

DOI： 10.18926/AMO/31849

治療後14年で肺転移をきたしたEwing肉腫の1例

米田泰史, 国定俊之, 田端雅弘, 二宮崇, 森本裕樹, 尾崎敏文

中部日本整形外科災害外科学会雑誌 52 ( 春季学会 ) 205 - 205 2009年3月

踵骨に発生した動脈瘤様骨嚢腫

三宅由晃, 国定俊之, 森本裕樹, 米田泰史, 小坂義樹, 尾﨑敏文

中部日本整形外科災害外科学会雑誌 52 ( 4 ) 971 - 972 2009年

Refraction-based 2D, 2.5D and 3D medical imaging: Stepping forward to a clinical trial 査読

Masami Ando, Hiroko Bando, Tokiko Endo, Shu Ichihara, Eiko Hashirnoto, Kazuyuki Hyodo, Toshiyuki Kunisada, Gang Li, Anton Maksimenko, Kensaku Mori, Daisuke Shimao, Hiroshi Sugiyama, Tetsuya Yuasa, Ei Ueno

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S32 - S36 2008年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

An attempt at refraction-based 2D, 2.5D and 3D X-ray imaging of articular cartilage and breast carcinoma is reported. We are developing very high contrast X-ray 2D imaging with XDFI (X-ray dark-field imaging), X-ray CT whose data are acquired by DEI (diffraction-enhanced imaging) and tomosynthesis due to refraction contrast. 2D and 2.5D images were taken with nuclear plates or with X-ray films. Microcalcification of breast cancer and articular cartilage are clearly visible. 3D data were taken with an X-ray sensitive CCD camera. The 3D image was successfully reconstructed by the use of an algorithm newly made by our group. This shows a distinctive internal structure of a ductus lactiferi (milk duct) that contains inner wall, intraductal carcinoma and multifocal calcification in the necrotic core of the continuous DCIS (ductal carcinoma in situ). Furthermore consideration of clinical applications of these contrasts made LIS to try tomosynthesis. This attempt was satisfactory from the view point of articular cartilage image quality and the skin radiation close. (C) 2008 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.ejrad.2008.04.033

X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery 査読

Toshiyuki Kunisada, Daisuke Shimao, Hiroshi Sugiyama, Ken Takeda, Toshifumi Ozaki, Masami Ando

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S18 - S21 2008年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejrad.2008.04.034

Shift-and-add tomosynthesis of a finger joint by X-ray dark-field imaging: Difference due to tomographic angle 査読

Daisuke Shimao, Toshiyuki Kunisada, Hiroshi Sugiyama, Masami Ando

EUROPEAN JOURNAL OF RADIOLOGY 68 ( 3 ) S27 - S31 2008年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER IRELAND LTD

A tomogram of a finger joint showing articular cartilage was generated based on X-ray dark-field imaging (XDFI) using the shift-and-add tomosynthesis algorithm. The experiment was performed at beamline 14B of the Photon Factory in Tsukuba, Japan, using synchrotron X-rays from a vertical wiggler. The incident X-ray energy was 36.0keV. The X-ray optics for XDFI comprised two Si crystals: an asymmetric Cut Si (2 2 0) monochromator-collimator and a 1.1-mm thick Si (2 2 0) Laue-case analyzer. The object was an intact cadaveric proximal interphalangeal joint fixed in formalin. Raw projection data were acquired by XDFI in a total of 41 views through an angle of 20 degrees in 0.5 degrees increments. The object and detector were synchronously rotated such that the fulcrum plane in the object and detector plane remained parallel. The X-ray dose for one piece of raw projection data was set to one-eleventh of that for one standard projection image by XDFI. Eleven views through an angle of 10 degrees in increments of 1 degrees of all 41 appropriately shifted raw projection data were added to produce arbitrary tomograms parallel to the fulcrum plane. We obtained a clear tomogram of the finger joint including the articular cartilage with the moderate artifact Peculiar to tomosynthesis. Consequently, arbitrary tomograms can be obtained for the same X-ray dose as that received for one standard projection image by XDFI. The fact that an inner structure such as articular cartilage, which is invisible to conventional X-ray imaging methods, has been Visualized on a tomogram with preserved refraction-enhanced contrast, is of considerable significance to clinical medicine. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ejrad.2008.04.037

ヒストン脱アセチル化酵素阻害剤とDNA脱メチル化剤の併用による滑膜肉腫細胞株に対する抗腫瘍効果の検討

佐藤千明, 吉田晶, 森本裕樹, 米田泰史, 佐々木剛, 国定俊之, 大内田守, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1228 - S1228 2008年8月

骨肉腫患者における葉酸代謝関連遺伝子の一塩基多型の検討

森本裕樹, 吉田晶, 大内田守, 米田泰史, 国定俊之, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S926 - S926 2008年8月

滑膜肉腫関連蛋白の細胞内局在に影響を与える薬剤および蛋白に関する検討

米田泰史, 大内田守, 神崎浩孝, 吉田晶, 佐々木剛, 森本裕樹, 国定俊之, 清水憲二, 尾崎敏文

日本整形外科学会雑誌 82 ( 8 ) S1023 - S1023 2008年8月

Photodynamic therapy with ATX-S10 center dot Na(II) inhibits synovial sarcoma cell growth 査読

Ken Takeda, Toshiyuki Kunisada, Shinichi Miyazawa, Yoshinori Nakae, Toshifumi Ozaki

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 466 ( 7 ) 1726 - 1733 2008年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Photodynamic therapy (PDT) is an effective cancer treatment modality that allows selective destruction of malignant tumor cells. We asked whether PDT could inhibit in vivo and in vitro growth of synovial sarcoma cells. We analyzed PDT using ATX-S10 center dot Na(II) and a diode laser for a synovial sarcoma cell line (SYO-1). Photodynamic therapy with ATX-S10 center dot Na(II) showed an in vitro cytotoxic effect on the cultured SYO-1 cells. The in vitro effect of PDT depended on the treatment concentration of ATX-S10 center dot Na(II) and the laser dose of irradiation. ATX-S10 center dot Na(II) was detected in the tumor tissue specimens that were excised from nude mice bearing SYO-1 within 6 hours after intravenous injection, but it was eliminated from the tumor 12 hours after injection. Photodynamic therapy suppressed the tumor growth of nude mice bearing SYO-1, and high-dose irradiation induced no viable tumor cells in histologic specimens. Photodynamic therapy performed after marginal resection of the tumor of nude mice bearing SYO-1 reduced the rate of local recurrence of the tumor. Our results suggest PDT using ATX-S10 center dot Na(II) and laser irradiation may be a potentially useful treatment for synovial sarcoma, especially to reduce the surgical margin and preserve critical anatomic structures adjacent to the tumor.

DOI： 10.1007/s11999-008-0284-6

橋本病を合併したMazabraud syndromeの1例

Single nucleotide polymorphism in reuced folate carrier-1 gene and methyleneterathydrofolate reductase gene in patients with osteosarcoma

Y. Morimoto, A. Yoshida, M. Ouchida, T. Kunisada, K. Shimizu, T. Ozaki

EJC SUPPLEMENTS 6 ( 9 ) 117 - 118 2008年7月

大畑範英, 森本裕樹, 吉田晶, 佐々木剛, 米田泰史, 国定俊之, 大内田守, 尾崎敏文

日本整形外科学会雑誌 82 ( 6 ) S853 - S853 2008年6月

Chondrosarcoma and PeroxisomeProliferator-Activated Receptor.

Nishida K, Kunisada T, Shen ZN, Kadota Y, Hashizume K, Ozaki T

PPAR Research 2008 1 - 7 2008年

New approach for assessing vascular distribution within bone tumors using dynamic contrast-enhanced MRI 査読

Yukio Kawakami, Toshiyuki Kunisada, Shinsuke Sugihara, Atsushi Ono, Keiichiro Nishida, Nobuhiro Abe, Akira Kawai, Kazuo Fujiwara, Yuki Morimoto, Toshifumi Ozaki

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 133 ( 10 ) 697 - 703 2007年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Purpose To differentiate benign from malignant bone tumors by analyzing the vascular distribution within bone tumors with dynamic contrast-enhanced MRI.
Methods We studied dynamic contrast-enhanced MRI for 49 bone tumors (22 malignant and 27 benign tumors). Seven small regions of interest (ROI) were set inside the largest portion of each tumor. Four ROI were placed evenly on the periphery and three ROI were placed evenly on the line of the longest breadth within the tumor. The slope of the curve (%Slope) was calculated on the time-intensity curves of the whole tumor and of each ROI. The variance values for the %Slope of the ROI were calculated to assess the dispersion of the intensity change at each ROI within the tumor.
Results Mean value of the %Slopes of whole tumor regions for malignant bone tumors (70.4 +/- 60.3%) was significantly higher than that for benign bone tumors (37.6 +/- 52.9%) (P = 0.015), although giant cell tumor (GCT), a locally aggressive tumor, had a relatively higher %Slope. Mean value of the variance of %Slopes for malignant bone tumors (3485.9 +/- 5942.5) was significantly higher than that for all benign tumors (470.4 +/- 583.9) (P = 0.012), indicating that the %Slope values of seven ROI within malignant bone tumors varied more widely compared with the ROI inside benign bone tumors. GCT also demonstrated a lower value.
Conclusion Our method of analyzing the signal intensity change at seven separate regions that evaluates the vascular distribution within a tumor could be a useful tool for differentiating between benign and malignant bone tumors.

DOI： 10.1007/s00432-006-0190-9

滑膜肉腫特異的転座型融合蛋白SS18-SSXおよびSS18、SSX蛋白の細胞内局在の解析

骨肉腫における6q16-23の高頻度染色体欠失の研究(High frequent allelic loss of chromosome 6q16-23 in osteosarcoma: Involvement of cyclin C in osteosarcoma)

大畑範英, 吉田晶, 伊藤佐智夫, 国定俊之, 森本裕樹, 神崎浩孝, 尾崎敏文, 清水憲二, 大内田守

日本癌学会総会記事 66回 345 - 345 2007年8月

米田泰史, 大内田守, 神崎浩孝, 国定俊之, 清水憲二, 尾崎敏文

日本整形外科学会雑誌 81 ( 8 ) S1119 - S1119 2007年8月

Refraction-enhanced tomosynthesis of a finger joint by X-ray dark-field imaging 査読

Daisuke Shimao, Toshiyuki Kunisada, Hiroshi Sugiyama, Masami Ando

JAPANESE JOURNAL OF APPLIED PHYSICS PART 2-LETTERS & EXPRESS LETTERS 46 ( 25-28 ) L608 - L610 2007年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INST PURE APPLIED PHYSICS

A finger joint tomogram based on X-ray dark-field imaging (XDFI) was demonstrated using the simplest shift-and-add tomosynthesis algorithm. Raw XDFI image data for tomosynthesis were acquired in a total of 11 views through 10 degrees, in increments of 1 degrees, by rotating the object and detector synchronously. Incident X-ray energy was monochromatic 36.0keV, derived from synchrotron radiation. The total dosage in acquiring 11 views for raw image data was equivalent to that of one XDFI image. A clear tomogram was obtained of a finger joint (including articular cartilage, which is invisible by conventional tomosynthesis) without an increase in X-ray dosage.

DOI： 10.1143/JJAP.46.L608

On detailed contrast of biomedical object in X-ray dark-field imaging 査読

Daisuke Shimao, Hiroshi Sugiyama, Toshiyuki Kunisada, Kazuyuki Hyodo, Koichi Mori, Masami Ando

SYNCHROTRON RADIATION INSTRUMENTATION, PTS 1 AND 2 879 1960 - + 2007年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）出版者・発行元：AMER INST PHYSICS

Over the past 10 years, refraction-based X-ray imaging has been studied together with a perspective view to clinical application. X-ray Dark-Field Imaging that utilizes a Laue geometry analyzer has recently been proposed and has the proven ability to depict articular cartilage in an intact human finger. In the current study, we researched detailed image contrast using X-ray Dark-Field Imaging by observing the edge contrast of an acrylic rod as a simple case, and found differences in image contrast between the right and left edges of the rod. This effect could cause undesirable contrast in the thin articular cartilage on the head of the phalanx. To avoid overlapping with this contrast at the articular cartilage, which would lead to a wrong diagnosis, we suggest that a joint surface on which articular cartilage is located should be aligned in the same sense as the scattering vector of the Lane case analyzer crystal. Defects of articular cartilage were successfully detected under this condition. When utilized under appropriate imaging conditions, X-ray Dark-Field Imaging will be a powerful tool for the diagnosis of arthropathy, as minute changes in articular cartilage may be early-stage features of this disease.

DOI： 10.1063/1.2436458

Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: Involvement of cyclin C in osteosarcoma 査読

Norihide Ohata, Sachio Ito, Aki Yoshida, Toshiyuki Kunisada, Kunihiko Numoto, Yoshimi Jitsumori, Hirotaka Kanzaki, Toshifumi Ozaki, Kenji Shimizu, Mamoru Ouchida

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18 ( 6 ) 1153 - 1158 2006年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PROFESSOR D A SPANDIDOS

The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.

軟部腫瘍のTlシンチグラフィ疑陽性例の検討

赤木史郎, 新家崇義, 郷原英夫, 佐藤修平, 黒田昌宏, 金澤右, 井谷智, 国定俊之, 尾崎敏文

核医学 43 ( 4 ) 354 - 354 2006年11月

Articular cartilage depicted at optimized angular position of Laue angular analyzer by X-ray dark-field imaging 査読

Daisuke Shimao, Hiroshi Sugiyama, Toshiyuki Kunisada, Masami Ando

APPLIED RADIATION AND ISOTOPES 64 ( 8 ) 868 - 874 2006年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Using 36.0 keV X-ray from synchrotron radiation, we examined the optimized angular position of Laue analyzer for depicting articular cartilage of an intact human finger by X-ray dark-field imaging. The surface of articular cartilage was depicted clearly by adopting the offset angle of 0.04 arcsec to lower angular side to the analyzer whilst the contour of articular cartilage was delineated clearly at the other angular positions of the analyzer within the width of the rocking curve. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2006.03.004

Accurate diagnosis of musculoskeletal lesions by core needle biopsy 査読

G Mitsuyoshi, N Naito, A Kawai, T Kunisada, A Yoshida, H Yanai, S Dendo, T Yoshino, S Kanazawa, T Ozaki

JOURNAL OF SURGICAL ONCOLOGY 94 ( 1 ) 21 - 27 2006年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

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 musculloskeletal 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.

DOI： 10.1002/jso.20504

Chromosomal and genetic imbalances in synovial sarcoma detected by conventional and microarray comparative genomic hybridization 査読

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

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 132 ( 7 ) 444 - 450 2006年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Purpose: To analyze the relationship between chromosomal instabilities and clinicopathological factors in synovial sarcoma (SS). Methods: Twenty-two fresh-frozen SS were analyzed by metaphase comparative genomic hybridization (CGH). Additional microarray CGH was performed in 13 cases. Results: Fourteen patients with SYT-SSX1 rearrangements and nine patients with biphasic tumor subtypes had better prognosis than the eight patients with SYT-SSX2 rearrangements and 13 patients with monophasic subtypes, respectively. Gains (average 3.0) were more frequent than losses (average 1.0). Frequent gains were identified on chromosomal regions 2, 6q, 7, 8q, 12, 17q, 18q, and 21q, whereas frequent losses were over-lapped on chromosomes 1p31-p35, 3p, 6q, 16, and 17p. High-level gains were observed on chromosomes 1q21-q31, 7, 8, 12, 17q, 18q, and 21q. Thirteen monophasic and nine biphasic tumors had an average of 5.1 and 2.8 aberrations, respectively. Patients with tumors harboring numerous aberrations (>= 3) had a worse clinical course. Microarray CGH more specifically detected genetic imbalances including gains in MDM2, MSH2, KCNK12, DCC, CDK2, ERBB3, SAS, and CDK4 and losses in HRAS, RASSF1, and CCND1. Gain of SAS was an important prognostic factor of SS. Conclusion: We have identified several factors influencing the prognosis of SS patients by metaphase and microarray CGH.

DOI： 10.1007/s00432-006-0089-5

Magnetic resonance angiography without contrast enhancement medium in bone and soft tissue tumors 査読

H Doi, A Ono, A Kawai, Y Morimoto, T Kunisada, E Nakata, T Ozaki

ONCOLOGY REPORTS 15 ( 3 ) 681 - 685 2006年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PROFESSOR D A SPANDIDOS

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 rnethod 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.

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

Y Nakagawa, A Yoshida, K Numoto, T Kunisada, D Wai, N Ohata, K Takeda, A Kawai, T 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）出版者・発行元：PROFESSOR D A SPANDIDOS

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 rnicroarray CGH.

Novel transdermal photodynamic therapy using ATX-S10・Na(II) induces apoptosis of synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice

Miyazawa S, Nishida K, Komiyama T, Nakae Y, Takeda K, Yorimitsu M, Kitamura A, Kunisada T, Ohtsuka A, Inoue H

Rheumatol. Int 2006年

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

S Arataki, K Tomizawa, A Moriwaki, K Nishida, M Matsushita, T Ozaki, T Kunisada, A Yoshida, H Inoue, H 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）出版者・発行元：MARY ANN LIEBERT INC

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 I 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.

DOI： 10.1089/neu.2005.22.398

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

X-ray dark-field Imaging and potential of its clinical application 査読

Daisuke Shimao, Hiroshi Sugiyama, Toshiyuki Kunisada, Anton Maksimenko, Fukai Toyofuku, Ei Ueno, Katsuhito Yamasaki, Chiho Obayashi, Kazuyuki Hyodo, Gang Li, Lin Pan, Xiaoming Jiang, Masami Ando

Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5745 ( I ) 32 - 39 2005年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

X-ray dark-field imaging (DFI) due to refraction is under development with intension of its clinical application. In this system we have adopted an asymmetric-cut monochro-collimator (M) and an angular analyzer (A) of Si 440 diffraction at around 35 keV of X-rays. By choosing an appropriate thickness T of A that satisfies the condition T = λN where λ is the extinction distance and N integer the transmissivity in the region of |W| (angular parameter) &lt
1 should be theoretically almost zero and |W| &gt
1 should be approximately 70-80%. This has been experimentally proven. Under this condition the X-rays whose propagation direction may not change such as those receiving only absorption will not go into the forward diffraction direction after A but go into the diffraction direction, while the X-rays refracted by object may go into the forward diffraction direction after A. We have settled two targets of clinical views: soft tissues at joints and early check of breast cancer. A first clear image of articular cartilage of small joint was successfully obtained using a proximal interphalangeal joint that was amputated from a cadaver. Since larger view field is needed for clinical use the size of approximately 90 mm in square has been successfully achieved. Using this beam articular cartilage of knee and shoulder joints from the same cadaver have been successfully visualized. Further visibility test by the DFI is under way for a phantom of breast cancer, paraffin fixed sliced breast samples containing micro-calcification, tumor and excised breast tissue.

DOI： 10.1117/12.595021

Clinical step onward with X-ray dark-field imaging and perspective view of medical applications of synchrotron radiation in Japan

Ando, M, Hashimoto, E, Hashizume, H, Hyodo, K, Inoue, H, Kunisada, T, Maksimenko, A, Mori, K, Rubenstein, E, Roberson, J, Shimao, D, Sugiyama, H, Takeda, K, Toyofuku, F, Ueno, E, Umetani, K, Wada, H, Pattanasiriwisawa, W

Nucl. Instrum. Methods. Phys. Res. A 548 ( 1-2 ) 1 - 16 2005年

The role of thallium-201 and pentavalent dimercaptosuccinic acid for staging cartilaginous tumours. 査読

Choong PF, Kunisada T, Slavin J, Schlicht S, Hicks R

International seminars in surgical oncology : ISSO 1 ( 1 ) 10 2004年11月

Construction of X-ray dark-field imaging with a view size of 80mm square and first visualization of human articular cartilage of femoral head under a nearly clinical condition 査読

Masami Ando, Hiroshi Sugiyama, Toshiyuki Kunisada, Daisuke Shimao, Ken Takeda, Hiroyuki Hashizume, Hajime Inoue

Japanese Journal of Applied Physics, Part 2: Letters 43 ( 9 ) L1175 - L1177 2004年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Field size of 80mm × 80mm for X-ray dark-field (DFI) imaging at 35keV using a 2.16-mm-thick 440 Laue diffraction analyzer has been achieved. Under this condition, only refracted X-rays from sample can transmit through this filter to form DFI while the beam that has not changed its direction is repelled to the diffraction direction. Its spatial resolution is 10 microns or better. An excised human femoral head in a water-filled vinyl bag simulating a clinical condition shows a high-contrast and high-spatial-resolution articular cartilage that has not been visualized by X-ray technique.

DOI： 10.1143/JJAP.43.L1175

Evaluation of X-ray dark-field imaging in visualization of nearly clinical articular cartilage 査読

D Shimao, H Sugiyama, K Hyodo, T Kunisada, M Ando

NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT 548 ( 1-2 ) 129 - 134 2004年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Angular dependence of visibility at articular cartilage of an intact human finger and knee by X-ray dark-field imaging (DFI) and bright-field imaging (BFI) was tested. These specimens were fixed by formalin. Good contrast of the articular cartilage has been obtained, as a preliminary result, not only by DFI but also by pseudo-DFI and BFI around the just Bragg angle of the angular analyzing crystal. This may indicate that it is useful for clinical purpose to use both DFI and BFI not only at just Bragg angle but also around it. (c) 2005 Elsevier B.V. All rights reserved.

Influence of telomerase activity on bone and soft tissue tumors 査読

N Umehara, T Ozaki, S Sugihara, T Kunisada, Y Morimoto, A Kawai, K Nishida, A Yoshida, T Murakami, H Inoue

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 130 ( 7 ) 411 - 416 2004年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Purpose. Telomeres consisting of a repeating nucleotide sequence (TTAGGG)n are shortened in normal somatic cells. Telomerase is an enzyme that elongates the telomere sequence and is detected in most human cancers and usually not in normal somatic cells. Little is known about telomerase activity in bone and soft tissue tumors. The aim of this study was to investigate the relationship between telomerase activity and clinical factors in bone and soft tissue tumors. Methods. Telomerase activity was measured using the modified telomeric repeat amplification protocol (TRAP) assay in 115 bone and soft tissue tumors obtained through open biopsy or resection. Results. Telomerase activity was detected in 10% of benign tumors and 44% of malignant tumors (p<0.001). A higher incidence of telomerase activity was detected in high-grade tumors than in low-grade tumors (p=0.002). The cumulative metastasis-free and overall survival in telomerase-positive patients was significantly worse than in telomerase-negative patients (p=0.045 and p=0.048). Conclusion. Our study suggests that telomerase activity is associated with tumor aggressiveness and may be a useful parameter to predict the prognosis of patients with malignant bone and soft tissue tumors.

DOI： 10.1007/s00432-004-0553-z

Reconstruction with ipsilateral fibula transfer with pasteurized bone after excision of bone sarcoma of the tibia 査読

Toshifumi Ozaki, Kazuo Fujiwara, Toshiyuki Kunisada, Tatsuo Ito, Akira Kawai, Hajime Inoue

Sarcoma 8 ( 2-3 ) 97 - 102 2004年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

We report a technique of implantation of the ipsilateral vascularized fibula with pasteurized recycled bone after excision of tibia sarcoma in two cases. Plate and screws were used for osteosynthesis of die tibia or talus, vascularized fibula, and pasteurized bone. Microsurgery is not necessary for this reconstruction technique. Two patients who underwent this technique have obtained good functional results without tumor relapse 5 and 6 years after operation. The technique produced excellent results with regard to tibial reconstruction in these cases. We found it to be simple, speedy, safe, and a low cost technique by use of recycled bone.

DOI： 10.1080/13577140400017794

Extended total sacrectomy and reconstruction for sacral tumor 査読

N Ohata, T Ozaki, T Kunisada, Y Morimoto, M Tanaka, H Inoue

SPINE 29 ( 6 ) E123 - E126 2004年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Study Design. This case report includes the results of long-term follow-up after extended total sacrectomy in a 13-year-old boy with a sarcoma originating in the sacrum with an extraskeletal extension and infiltration into the left ilium.
Objective. To report and discuss a case of sacral tumor treated by extended sacrectomy.
Summary of Background Data. Sacral tumors are often at an advanced stage with a large volume at diagnosis. Although total or extended sacrectomy is the only radical means to treat the massive sacral tumor, unavoidable complications in total sacrectomy are serious in the treatment selection.
Methods. Initial histologic findings indicated a synovial sarcoma. Additional genetic analysis redesignated the tumor as an unclassified sarcoma. Preoperative neoadjuvant chemotherapy and radiotherapy were completed. The response to the preoperative treatment appeared as a reduction in tumor size ( approximately 50%) on radiographs. After extended sacrectomy, the L5 vertebral body was fixed between the ilia, and the pelvic ring was compressed by the Zielke system. The ISOLA instrumentation system connected the lumbar spine and both ilia. All sacral nerve roots and the L5 root on the left side were cut.
Results. At the 5-year follow-up examination, the patient was disease- free, could walk with crutches, and could climb stairs using the handrail and one crutch.
Conclusions. The patient's excellent response to preoperative antitumor treatment was considered crucial to the long-term outcome. But the decision between a radical resection with reconstruction and a less extensive procedure with combined therapy remains controversial.

Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization.

Ozaki T, Nakagawa Y, Yoshida A, Numoto K, Sugihara S, Kunisada T, Hamazaki S, Inoue H

CANCER GENOMICS & PROTEMICS 2004年

孤立性骨嚢腫の治療成績

中川寧子, 尾崎敏文, 国定俊之, 伊藤達男, 井上一

中部日本整形外科災害外科学会雑誌 46 ( 秋季学会 ) 46 - 46 2003年9月

SYT蛋白とSSX蛋白のyeast two hybrid assayを用いた機能解析

伊藤達男, 大内田守, 尾崎敏文, 国定俊之, 森本裕樹, 大畑範英, 中川寧子, 吉田晶, 伊藤佐智夫, 清水憲二

日本癌学会総会記事 62回 536 - 536 2003年8月

ある種の分子標的薬はSYT-SSX発現細胞株に特異的な抗腫瘍効果を発揮する

沼本邦彦, 伊藤達男, 尾崎敏文, 大内田守, 国定俊之, 伊藤佐智夫, 森本裕樹, 大畑範英, 中川寧子, 清水憲二, 井上一

日本整形外科学会雑誌 77 ( 8 ) S1086 - S1086 2003年8月

滑膜肉腫に認められる転座遺伝子SYT-SSXのtwo hybrid assayを用いた機能解析

伊藤達男, 尾崎敏文, 大内田守, 国定俊之, 森本裕樹, 大畑範英, 中川寧子, 武田健, 沼本邦彦, 吉田晶, 伊藤佐智夫, 清水憲二, 井上一

日本整形外科学会雑誌 77 ( 6 ) S823 - S823 2003年6月

融合遺伝子診断の利点と欠点

森本裕樹, 尾崎敏文, 国定俊之, 井上一

中部日本整形外科災害外科学会雑誌 46 ( 6 ) 1067 - 1068 2003年

骨軟部腫瘍におけるレセプターチロシンキナーゼ(c-kit)の発現

吉田晶, 川井章, 内藤訓子, 森本裕樹, 伊藤達男, 大畑範英, 国定俊之, 尾崎敏文, 別府保男

日本癌学会総会記事 61回 397 - 397 2002年10月

Co-expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in cartilaginous tumours: a marker for malignancy? 査読

T Kunisada, JM Moseley, JL Slavin, TJ Martin, PFM Choong

PATHOLOGY 34 ( 2 ) 133 - 137 2002年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CARFAX PUBLISHING

Aim: Parathyroid hormone-related protein (PTHrP) is one of the critical factors for the differentiation and growth of chondrocytes. We examined the correlation between the co-expression of PTHrP and PTH/PTHrP receptor and the grade of malignancy in cartilaginous tumours.
Methods: We analysed PTHrP and PTH/PTHrP receptor expression in chondrosarcoma by immunohistochemistry and compared specific staining with the expression in benign cartilaginous tumours. There were 38 cartilaginous bone tumours consisting of 26 chondrosarcoma, six enchondroma and six osteochondroma. Chondrosarcoma were composed of 20 conventional chondrosarcoma (10 grade 1, seven grade 2, and three grade 3), two dedifferentiated chondrosarcoma, two clear cell chondrosarcoma, and two myxoid chondrosarcoma. We performed the standard peroxidase-labelled streptavidin-biotin detection method for immunohistochemistry using an antibody raised against PTHrP (1-14) and PTH/PTHrP receptor. The magnitude of receptor positivity of PTHrP and PTH/PTHrP in each tumour was assessed as a percentage of PTHrP and PTH/PTHrP-positive cells per thousand tumour cells in the most histologically aggressive area of the tumour.
Results: All chondrosarcoma, five of six enchondroma, and four of six osteochondroma showed PTHrP-positive cells, and all chondrosarcoma, five of six enchondroma and five of six osteochondroma showed PTHrP receptor-positive cells. The grade of malignancy correlated with the percentage of both PTHrP and PTH/PTHrP receptor-positive tumour cells (P<0.0001, either). Each grade of chondrosarcoma showed statistically higher expression of both PTHrP and PTH/PTHrP receptor than benign cartilaginous tumour.
Conclusion: This is the first report of the co-expression of PTHrP and PTH/PTHrP receptor in chondrosarcoma. PTHrP and PTH/PTHrP receptor positivity may be valuable for differentiating between benign and malignant cartilaginous tumours.

DOI： 10.1080/003130201201117936

Endostatin inhibits adhesion of endothelial cells to collagen I via alpha(2)beta(1) integrin, a possible cause of prevention of chondrosarcoma growth 査読

T Furumatsu, N Yamaguchi, K Nishida, A Kawai, T Kunisada, M Namba, H Inoue, Y Ninomiya

JOURNAL OF BIOCHEMISTRY 131 ( 4 ) 619 - 626 2002年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE BIOCHEMICAL SOC

Endostatin derived from collagen XVIII is a potent endogenous anti-angiogenic factor that induces regression of various tumors of epithelial origin. Endostatin has been shown to inhibit endothelial cell functions, however, its effect remains controversial. We first attempted here to apply the inhibitory effect of recombinant human endostatin on chondrosarcomas, which originate from the mesenchyme, in nude mice. Endostatin induced reduction of chondrosarcoma growth and tumor angiogenesis in vivo. However, endostatin showed no effect on the proliferation and migration of chondrosarcoma cells in vitro. Next, we investigated the interactions between endostatin and endothelial cells in detail. Endostatin inhibited the migration on and attachment to collagen I but did not affect the proliferation of endothelial cells. Although the migration of endothelial cells was stimulated by angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor, endostatin showed similar inhibitory effects on it in the presence and absence of the stimulants. Moreover, the inhibitory effect against endothelial cell attachment to collagen I was attenuated or modulated in the presence of neutralizing antibodies of alpha(2), alpha(5)beta(1), and alpha(V)beta(3) integrins but not that of alpha(1) integrin. Our results suggest that endostatin might suppress the alpha(2)beta(1) integrin function of endothelial cells via alpha(5)beta(1), or alpha(V)beta(3), integrin. We propose here that endostatin might be effective for anti-angiogenic therapy for human chondrosarcomas through the suppression of alpha(2)beta(1) integrin functions in endothelial cells.

Wound complications following pre-operative radiotherapy for soft tissue sarcoma 査読

T Kunisada, SY Ngan, G Powell, PFM Choong

EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 28 ( 1 ) 75 - 79 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：W B SAUNDERS CO LTD

Aims: We analysed wound complications in 43 patients with soft tissue sarcoma who were treated with combined pre-operative radiotherapy and surgery
Methods: All patients received the same protocol of pre-operative radiotherapy at our institution.
Results: Thirty-six (84%) patients developed acute skin toxicity following radiotherapy. After wide local excision, 15 patients required primary soft tissue reconstruction with vascularized muscle transfer and four patients underwent free skin flap to enable wound closure as part of their primary surgery. Nineteen patients (44%) developed postoperative wound complications including 10 (23%) patients who required an additional surgical procedure. Four (27%) patients developed flap necrosis in a group of 15 who underwent primary vascularized soft tissue transfer. All required a second vascularized muscular flap. One elderly patient, who had grade 3 acute radiation skin toxicity, had an arterial graft and total hip arthroplasty for a femoral artery aneurysm and an avascular necrosis of the hip, respectively. In our series, age ( 40 years) was the only impact factor influencing wound complication after surgery following radiotherapy (P=0.06).
Conclusions: Site of tumour, radiation field size, surgical resection volume, grade of acute radiation toxicity, comorbidity, and smoking were not demonstrated to have predictive value in wound complication following preoperative radiotherapy. Although previous papers suggested that vascularized soft tissue transfer could be useful reducing wound morbidity, our results could not confirm this. (C) 2002 Harcourt Publishers Ltd.

DOI： 10.1053/ejso.2001.1213

Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-gamma.

Nishida K, Furumatsu T, Takada I, Kawai A, Yoshida A, Kunisada T, Inoue H

Br J Cancer 2002年

Reconstruction of the proximal humerus with the clavicle after tumor resection: a case report.

Ozaki T, Hashizume H, Kunisada T, Kawai A, Nishida K, Sugihara S, Inoue H

Clin Orthop 2001年

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA classⅠallele

Hiraki A, Ikeda K, Yoshino T, Kaneshige T, Kiura K, Kunisada T, Fujiwara K, Tanimoto M, Harada M

Biochem Biophys Res Comm 2001年

Major reconstruction for periacetabular metastasis - Early complications and outcome following surgical treatment in 40 hips 査読

T Kunisada, PFM Choong

ACTA ORTHOPAEDICA SCANDINAVICA 71 ( 6 ) 585 - 590 2000年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TAYLOR & FRANCIS AS

We performed 40 total hip arthroplasties with pelvic reconstruction in 37 patients with metastatic periacetabular tumor. 3 patients underwent bilateral periacetabular reconstructive surgery and 2 of these had bilateral procedures at the single operation. There were 8 Harrington class I, 7 class II, and 25 class III lesions, A modified Harrington procedure was employed. All patients showed improvements in hip pain, analgesic use, ambulation and mobility postoperatively, 1 prosthetic dislocation occurred after a fall at home 2 months fallowing surgery. 2 patients had pulmonary emboli during the femoral procedure, 1 of whom died during surgery. There mere no prosthetic loosenings. Preoperative CT and/or MRI are important for the study of metastatic involvement of acetabular bone, Durability of reconstruction requires appropriate use of acetabular mesh, Steinmann pins, acetabular reinforcement rings and long-stem femoral prostheses. Careful patient selection may improve quality of life. A sequential bilateral procedure should be considered for some patients.

Synovial sarcoma with a large hematoma in the inguinal region 査読

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

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 120 ( 9 ) 533 - 534 2000年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER-VERLAG

We report the case of a patient with synovial sarcoma and a large hematoma of the inguinal region. The patient underwent tumor resection of the lower 2/3 of the acetabulum after preoperative chemotherapy. Twenty-four months after surgery, she is alive without any relapse and can walk without support.

Giant schwannoma of the back 査読

Eiichi Takada, Toshifumi Ozaki, Toshiyuki Kunisada, Yoshiaki Harada, Hajime Inoue

Archives of Orthopaedic and Trauma Surgery 120 ( 7-8 ) 467 - 469 2000年

Electrophoretic and serologic characterization of 56 kDa antigen (M56) with autologous serum derived from a chondrosarcoma patient: A shared antigen of immunoresponses in cancer and autoimmune diseases 査読

K Fujiwara, H Udono, T Kunisada, A Kawai, H Inoue, M Takigawa, M Namba, E Nakayama

ELECTROPHORESIS 20 ( 17 ) 3335 - 3342 1999年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-V C H VERLAG GMBH

We investigated whether antibodies specific to autologous cancer cells are produced in the peripheral blood of patients with chondrosarcoma. There have been few reports on the investigation of the immune responses, such as autologous antibody production, to chondrosarcoma. Here, tumor-associated antigens were separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and detected by immunoenzymatic amplification. A 56 kDa molecule (M56) was detected in the serum from patients' peripheral blood. M56 is ubiquitously expressed in various kinds of tissue-derived cells. However, the molecule seemed to be retained mostly in the cytosolic compartment of lymphoid cells, while it was expressed on the cell surface of nonlymphoid cancer cells. Furthermore, the antibodies reactive to the 56 kDa molecule were frequently observed in sera derived from patients with other cancers and autoimmune diseases as compared to the sera from healthy control donors, suggesting that M56 is a common target molecule of immune responses in patients with various cancers and autoimmune diseases.

Insertion of the patella tendon after prosthetic replacement of the proximal tibia 査読

T Ozaki, T Kunisada, A Kawai, Y Takahara, H Inoue

ACTA ORTHOPAEDICA SCANDINAVICA 70 ( 5 ) 527 - 529 1999年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SCANDINAVIAN UNIVERSITY PRESS

We describe the technique and the results of a method to reconstruct the patellar tendon insertion to a tumor prosthesis by wrapping an artificial mesh around the prosthesis, followed by suturing the patellar tendon and a gastrocnemius flap to the mesh.

Imaging assessment of the responses of osteosarcoma patients to preoperative chemotherapy - Angiography compared with thallium-201 scintigraphy 査読

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

CANCER 86 ( 6 ) 949 - 956 1999年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

BACKGROUND. Assessment of the responses of osteosarcoma patients to preoperative chemotherapy is of clinical importance. The purpose of this study was to estimate the accuracy of angiography and thallium-201 scintigraphy, compared with histology, in assessing the responses of patients with osteosarcoma to preoperative chemotherapy.
METHODS, Nineteen patients with osteosarcoma who were diagnosed between 1992 and 1997 were studied. The findings of angiography and thallium-201 scintigraphy before and after preoperative chemotherapy were compared with the percentage of necrosis of tumor cells and the response grade as determined histologically. Quantitative analysis of the isotopic uptake by thallium-201 scintigraphy before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis.
RESULTS, Angiography yielded a sensitivity of 88%, a specificity of 73%, and a predictive accuracy of positive test of 70%, whereas thallium-201 scintigraphy achieved 88%, 100%, and 100%, respectively. Both angiographic and scintigraphic assessment showed a significant correlation with response grade as determined histologically (P < 0.05 and P < 0.0003, respectively). The alteration ratio of thallium-201 scintigraphy showed a strong, highly significant correlation with the percentage of tumor necrosis (P < 0.0001).
CONCLUSIONS. A change in the tumor uptake of thallium-201 scintigraphy after preoperative chemotherapy can predict the tumor necrosis in osteosarcoma precisely. Thallium scintigraphy is a noninvasive technique and seems to be more useful than angiography in assessing the response of osteosarcoma to preoperative chemotherapy. (C) 1999 American Cancer Society.

Reconstruction of the hip abductors after resection of the proximal femur 査読

T Ozaki, S Kaneko, T Kunisada, A Kawai, T Dan'ura, N Naito, H Inoue

INTERNATIONAL ORTHOPAEDICS 23 ( 3 ) 182 - 183 1999年8月

Angiography for assessment of preoperative chemotherapy in musculoskeletal sarcomas 査読

J Fujii, T Ozaki, A Kawai, T Kunisada, S Sugihara, H Inoue

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH ( 360 ) 197 - 206 1999年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Eleven abnormal findings of digital subtraction angiography were analyzed in 25 patients with bone sarcoma and in 23 patients with soft tissue sarcoma. The relation between digital subtraction angiographic findings and the histologic effect of chemotherapy was evaluated. Digital subtraction angiography was performed with the patient under local anesthesia with the Seldinger technique, using an ADVANT X unit. Contrast medium was injected at a rate of 4 to 6 mi per second, with the usual single bolus dose of approximately 6 to 8 mi. Eleven abnormal findings included tumor stain, hypervascularity, arterial distortion, vascular stretch, arterial dilatation, arteriovenous shunt, arterial encasement, occlusion, blood pool, caliber with irregular wall, and dilatation of draining vein. Each finding after preoperative chemotherapy was compared with that before chemotherapy and divided into three grades; Grade I, not effective; Grade 2, effective; and Grade 3, very effective. Angiographic Grades 2 and 3 were defined as responders. The histologic effect was examined and scored according to the modified classification proposed by Huvos. Histologic Grades 1 and 2 were classified as nonresponders and Grades 3 and 4 as good responders. In bone sarcomas, hypervascularity and tumor stain were seen in all patients. In soft tissue sarcomas, tumor stain was shown in all 23 patients and hypervascularity was seen in 21 patients. Tumor stain, hypervascularity, vascular stretch, and arterial encasement were correlated closely with histologic findings and showed an accuracy equal to or greater than 70%. When these four findings changed to angiographic Grade 3 after preoperative chemotherapy, 90% of patients had good histologic outcome.

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

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年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

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 査読

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年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

INTERNATIONAL JOURNAL OF CANCER 77 ( 6 ) 854 - 859 1998年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B 7 ( 3 ) 199 - 202 1998年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

ACTA MEDICA OKAYAMA 52 ( 1 ) 67 - 70 1998年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

国定俊之, 尾崎敏文, 土井武, 檀浦智幸, 井上一

中国・四国整形外科学会雑誌 10 ( 2 ) 285 - 288 1998年

記述言語：日本語出版者・発行元：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 査読

T Kunisada, A Kawai, H Inoue, M Namba

ACTA MEDICA OKAYAMA 51 ( 3 ) 135 - 140 1997年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH ( 337 ) 216 - 225 1997年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

ACTA MEDICA OKAYAMA 51 ( 2 ) 87 - 92 1997年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY 115 ( 2 ) 68 - 70 1996年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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 査読

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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年

記述言語：英語出版者・発行元：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

当科における好酸球性肉芽腫の検討

正岡俊二, 川井章, 杉原進介, 国定俊之, 井上一

中国・四国整形外科学会雑誌 8 ( 2 ) 435 - 439 1996年

記述言語：日本語出版者・発行元：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. 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. 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

良性骨腫ように対する合成ハイドロキシアパタイトの使用経験

国定俊之, 川井章, 杉原進介, 西田圭一郎, 濱田全紀, 井上一

中国・四国整形外科学会雑誌 7 ( 1 ) 7 - 12 1995年

記述言語：日本語出版者・発行元：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