Updated on 2022/05/16

写真a

 
IKUTA Kunihiro
 
Organization
Nagoya University Hospital Orthopedics Assistant professor of hospital
Title
Assistant professor of hospital

Degree 1

  1. 医学博士 ( 2015.3   名古屋大学 ) 

Research Areas 1

  1. Life Science / Orthopedics

 

Papers 64

  1. Diffusion-Weighted Magnetic Resonance Imaging Improves the Accuracy of Differentiation of Benign from Malignant Peripheral Nerve Sheath Tumors

    Koike Hiroshi, Nishida Yoshihiro, Ito Shinji, Shimoyama Yoshie, Ikuta Kunihiro, Urakawa Hiroshi, Sakai Tomohisa, Shimizu Koki, Ito Kan, Imagama Shiro

    WORLD NEUROSURGERY   Vol. 157   page: E207 - E214   2022.1

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    Language:Japanese   Publisher:World Neurosurgery  

    Objective: In patients with neurofibromatosis type 1 (NF1), it is important to accurately determine when plexiform neurofibroma (pNF) transforms to a malignant peripheral nerve sheath tumor (MPNST). The purpose of this study is to investigate the usefulness of diffusion-weighted imaging (DWI) in differentiating pNF and MPNST in NF1 patients. Methods: Among the NF1 patients who were referred to our hospital between 1985 and 2015, 10 cases of MPNST and 19 cases of pNF were included. We evaluated features of standard magnetic resonance imaging according to the differentiation criteria of malignancy from benignancy as previously reported, apparent diffusion coefficient (ADC) value based on the DWI and the correlation between ADC value and benignancy/malignancy. ROC analysis was performed to determine the appropriate cutoff value of ADC. Results: There were significant differences between MPNST and pNF in the size of the tumor (P = 0.009), peripheral enhancement pattern (P = 0.002), perilesional edema-like zone (P = 0.0008), and intratumoral cystic change (P = 0.02). The mean and minimum values of ADC were significantly lower in MPNST than those in pNF (P = 0.03 and P = 0.003, respectively). When we set a cutoff value of mean ADC as 1.85 × 10–3 mm2/s, the sensitivity and specificity were 80% and 74%, respectively. The area under the curve value improved by adding the Wasa score to the mean ADC evaluation. Conclusions: ADC values determined by DWI are useful in differentiating MPNST from pNF and adding ADC evaluation to standard MRI evaluation improved the diagnostic accuracy.

    DOI: 10.1016/j.wneu.2021.09.130

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  2. Successful treatment with denosumab for pelvic fibrous dysplasia A case report and review of the literature

    Ikuta Kunihiro, Sakai Tomohisa, Koike Hiroshi, Ito Kan, Imagama Shiro, Nishida Yoshihiro

    MEDICINE   Vol. 100 ( 49 ) page: e28138   2021.12

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    Language:Japanese   Publisher:Medicine (United States)  

    Rationale:Fibrous dysplasia is a rare disorder that results in fractures, pain, and disability and can affect any bone in the body. The treatment of symptomatic fibrous dysplasia is determined based on the affected bones. Although some lesions are often too extensive for surgical procedures, there are currently no effective or recommended medical treatments available for them.Patient concerns:A 27-year-old woman developed right buttock pain and was diagnosed with a bone tumor in the right ilium. Clinical images revealed an expansive osteolytic lesion with thinning of the cortex and cystic change from the acetabulum to the sacroiliac joint.Diagnosis:An incisional biopsy was performed, and the lesion was diagnosed as cystic fibrous dysplasia. Occasional osteoclast-like giant cells and woven bone were observed. The patient had no evidence of polyostotic lesions or findings of McCune-Albright syndrome. Biochemical blood test results showed no obvious abnormal values, except for an increase in serum tartrate-resistant acid phosphatase 5b to 459 mU/dL.Interventions:Since surgical treatment appeared to be challenging, she was treated with denosumab with decreased dose-intensity schedules.Outcomes:The administration of denosumab caused osteosclerosis within the lesion, resulting in the elimination of bone pain. The patient received denosumab treatment for 18 months. Pain relief and lesion radiodensity were maintained for 9 months after denosumab discontinuation. The serum level of tartrate-resistant acid phosphatase 5b was measured to monitor the response to denosumab, which was suppressed during denosumab treatment.Lessons:We described successful denosumab treatment in a patient with cystic fibrous dysplasia (FD) who maintained efficacy for 9 months after treatment. Although the use of denosumab in fibrous dysplasia is currently off-label, our experience with this patient supports the potential of denosumab therapy for patients for whom surgical treatment is challenging.

    DOI: 10.1097/MD.0000000000028138

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  3. Reconstruction of the extensor mechanism augmented with reverse transferred iliotibial band after proximal tibia tumor resection and mega-prosthetic replacement

    Ikuta Kunihiro, Nishida Yoshihiro, Tsukushi Satoshi, Sakai Tomohisa, Koike Hiroshi, Imagama Shiro

    KNEE   Vol. 33   page: 102 - 109   2021.12

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    Background: The optimal procedure for functional reconstruction of the extensor mechanism after proximal tibia mega-prosthetic replacement remains unclear. Methods: Since 2006, 14 consecutive patients with aggressive bone tumors in the proximal tibia who underwent mega-prosthetic replacement were prospectively treated with reconstruction of the extensor mechanism using an ipsilateral iliotibial band. The surgical procedure consisted of wrapping the reversed iliotibial band around the tibia component, firmly suturing it to the remaining patellar tendon and tibialis anterior fascia, and covering it with a muscle flap. At the last follow up, the function was assessed based on extensor lag, active flexion of the knee, and Musculoskeletal Tumor Society score. Patellar height was measured with the Insall–Salvati ratio (ISR) preoperatively, postoperatively, and at the last follow up. Results: At the last follow up, the extensor lag and active flexion in 14 patients averaged 2.5° and 86°, respectively. Musculoskeletal Tumor Society score could be obtained in nine surviving patients at the last follow up and was a mean of 20.7 points. The mean ISR preoperatively, postoperatively, and at the last follow up was 1.04, 0.75, and 0.89, respectively. The extensor lag was not associated with the ISR value at any points, while reduced active flexion significantly correlated with a low ISR at the last follow up (P = 0.015). Four patients underwent additional surgeries due to postoperative infection, but none required eventual revision or amputation. Conclusion: The extensor mechanism reconstruction with the reverse transferred iliotibial band for mega-prosthetic replacement after proximal tibia resection yielded reliable outcomes with functional benefit to stabilize active knee extension.

    DOI: 10.1016/j.knee.2021.09.006

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  4. Effect of hydroxyapatite tubes on the lag screw intraoperative insertion torque for the treatment of intertrochanteric femoral fractures

    Iwata H., Takada N., Kuroyanagi G., Ikuta K., Usami T., Sekiya I., Murakami H.

    Injury   Vol. 52 ( 11 ) page: 3377 - 3381   2021.11

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    Background: Hydroxyapatite (HA) augments are frequently used in orthopedic surgery. However, the effectiveness of HA augments on the treatment of intertrochanteric femoral fractures remains unknown. This study aimed to investigate whether the use of HA tubes affects the intraoperative insertion torque of the lag screw during intertrochanteric femoral fracture surgery. Methods: From January 2016 to October 2020, 58 patients with intertrochanteric femoral fractures were included and divided into the HA treatment group (HA group, n = 29) and non-HA treatment group (N group, n = 29). Patients with intertrochanteric femoral fractures were treated using the Gamma3 nail system® with or without two HA tubes. HA tubes were inserted into the femoral head through the lag screw hole before the insertion of the lag screw. The mean and maximum intraoperative insertion torques of the lag screw, bone mineral density (BMD) of the uninjured opposite side femoral neck, and tip apex distance (TAD) of the lag screw on postoperative radiographs were assessed. To assess the loss of reduction after the surgery, we investigated the amounts of telescoping of the lag screw and the changes in the neck shaft angle. Results: The mean and maximum insertion torques were correlated with BMD in the HA and N groups, respectively. The mean and maximum insertion torques were not correlated with TAD in the HA and N groups, respectively. The mean torque/BMD ratio was significantly higher in the HA group than in the N group (p = 0.03). There were no significant differences in the maximum torque/BMD ratio between HA and N groups (p = 0.06), while the maximum torque/BMD ratio tended to be higher in the HA group than in the N group. The amounts of telescoping of the lag screw in the HA group were significantly lower than that in the N group (p = 0.04), while there were no significant differences in the changes in the neck shaft angle between two groups (p = 0.32). Conclusion: Our results strongly suggest that the use of HA tubes increases the intraoperative lag screw insertion torque/BMD ratio and may improve the lag screw fixation by strengthening the bone/metal thread interface in the treatment of intertrochanteric femoral fractures.

    DOI: 10.1016/j.injury.2021.07.032

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  5. S100-negative epithelioid malignant peripheral nerve sheath tumor with possible perineurial differentiation

    Yamashita Kyoko, Funauchi Yuki, Hayakawa Keiko, Ae Keisuke, Matsumoto Seiichi, Ikuta Kunihiro, Nishida Yoshihiro, Ueno Teruko, Shimoyama Yoshie, Hiruta Nobuyuki, Machinami Rikuo, Kawachi Hiroshi, Takeuchi Kengo

    VIRCHOWS ARCHIV     2021.10

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    Epithelioid malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of MPNST composed of epithelioid cells with abundant cytoplasm. Currently, strong and diffuse immunostaining for S100 protein and SOX10 is generally regarded as a characteristic feature of epithelioid MPNST. However, malignant tumors with epithelioid morphology that arise from a peripheral nerve or a pre-existing benign nerve sheath tumor should be regarded as epithelioid MPNSTs when they do not show characteristic features that definitively lead to other specific diagnoses. Here, we describe 3 cases of epithelioid MPNST in the peripheral nerve or schwannoma that was negative for S100 protein and SOX10 expression. Instead, these tumors were positive for EMA, GLUT1, claudin 1, and cytokeratin to varying degrees, while all of them retained SMARCB1 and H3K27me3 by immunohistochemistry. EMA, GLUT1, and claudin 1 are known markers of perineurial cell differentiation; thus, they could possibly represent epithelioid MPNST with perineurial cell differentiation.

    DOI: 10.1007/s00428-021-03218-y

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  6. Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

    Jahagirdar Deepa, Walters Magdalene K., Novotney Amanda, Brewer Edmond D., Frank Tahvi D., Carter Austin, Biehl Molly H., Abbastabar Hedayat, Abhilash E. S., Abu-Gharbieh Eman, Abu-Raddad Laith Jamal, Adekanmbi Victor, Adeyinka Daniel Adedayo, Adnani Qorinah Estiningtyas Sakilah, Afzal Saira, Aghababaei Soodabeh, Ahinkorah Bright Opoku, Ahmad Sajjad, Ahmadi Keivan, Ahmadi Sepideh, Ahmadpour Ehsan, Ahmed Muktar Beshir, Rashid Tarik Ahmed, Salih Yusra Ahmed, Aklilu Addis, Akram Tayyaba, Akunna Chisom Joyqueenet, Al Hamad Hanadi, Alahdab Fares, Alanezi Fahad Mashhour, Aleksandrova Ekaterina A., Alene Kefyalew Addis, Ali Liaqat, Alipour Vahid, Almustanyir Sami, Alvis-Guzman Nelson, Ameyaw Edward Kwabena, Amu Hubert, Andrei Catalina Liliana, Andrei Tudorel, Anvari Davood, Arabloo Jalal, Aremu Olatunde, Arulappan Judie, Atnafu Desta Debalkie, Quintanilla Beatriz Paulina Ayala, Ayza Muluken Altaye, Azari Samad, Darshan B. B., Banach Maciej, Barnighausen Till Winfried, Barra Fabio, Barrow Amadou, Basu Sanjay, Bazargan-Hejazi Shahrzad, Belay Habtamu Gebrehana, Berheto Tezera Moshago, Bezabhe Woldesellassie Mequanint, Bezabih Yihienew Mequanint, Bhagavathula Akshaya Srikanth, Bhardwaj Nikha, Bhardwaj Pankaj, Bhattacharyya Krittika, Bibi Sadia, Bijani Ali, Bisignano Catherine, Bolarinwa Obasanjo Afolabi, Boloor Archith, Boltaev Azizbek A., Briko Nikolay Ivanovich, Buonsenso Danilo, Burkart Katrin, Butt Zahid A., Cao Chao, Charan Jaykaran, Chatterjee Souranshu, Chattu Soosanna Kumary, Chattu Vijay Kumar, Choudhari Sonali Gajanan, Dinh-Toi Chu, Couto Rosa A. S., Cowden Richard G., Dachew Berihun Assefa, Dadras Omid, Dagnew Amare Belachew, Dahlawi Saad M. A., Dai Xiaochen, Dandona Lalit, Dandona Rakhi, das Neves Jose, Degenhardt Louisa, Demeke Feleke Mekonnen, Desta Abebaw Alemayehu, Deuba Keshab, Dhamnetiya Deepak, Dhungana Govinda Prasad, Dianatinasab Mostafa, Diaz Daniel, Djalalinia Shirin, Linh Phuong Doan, Dorostkar Fariba, Edinur Hisham Atan, Effiong Andem, Eftekharzadeh Sahar, Zaki Maysaa El Sayed, Elayedath Rajesh, Elhadi Muhammed, El-Jaafary Shaimaa I, El-Khatib Ziad, Elsharkawy Aisha, Endalamaw Aklilu, Endries Aman Yesuf, Eskandarieh Sharareh, Ezeonwumelu Ifeanyi Jude, Ezzikouri Sayeh, Farahmand Mohammad, Faraon Emerito Jose A., Fasanmi Abidemi Omolara, Ferrero Simone, Desideri Lorenzo Ferro, Filip Irina, Fischer Florian, Folayan Morenike Oluwatoyin, Foroutan Masoud, Fukumoto Takeshi, Gad Mohamed M., Gadanya Muktar A., Gaidhane Abhay Motiramji, Garg Tushar, Gayesa Reta Tsegaye, Gebreyohannes Eyob Alemayehu, Gesesew Hailay Abrha, Obsa Abera Getachew, Ghadiri Keyghobad, Ghashghaee Ahmad, Gilani Syed Amir, Ginindza Themba G., Glavan Ionela-Roxana, Glushkova Ekaterina Vladimirovna, Golechha Mahaveer, Gugnani Harish Chander, Gupta Bhawna, Gupta Sapna, Gupta Veer Bala, Gupta Vivek Kumar, Hamidi Samer, Handanagic Senad, Haque Shafiul, Harapan Harapan, Hargono Arief, Hasaballah Ahmed I, Hashi Abdiwahab, Hassan Shoaib, Hassanipour Soheil, Hayat Khezar, Heredia-Pi Ileana, Hezam Kamal, Holla Ramesh, Hoogar Praveen, Hoque Mohammad Enamul, Hosseini Mostafa, Hosseinzadeh Mehdi, Hsairi Mohamed, Hussain Rabia, Ibitoye Segun Emmanuel, Idrisov Bulat, Ikuta Kevin S., Ilesanmi Olayinka Stephen, Ilic Irena M., Ilic Milena D., Irvani Seyed Sina Naghibi, Islam M. Mofizul, Ismail Nahlah Elkudssiah, Itumalla Ramaiah, Iyamu Ihoghosa Osamuyi, Jabbarinejad Roxana, Jain Vardhmaan, Jayawardena Ranil, Jha Ravi Prakash, Joseph Nitin, Kabir Ali, Kabir Zubair, Kalhor Rohollah, Kaliyadan Feroze, Kamath Ashwin, Kanchan Tanuj, Kandel Himal, Kassahun Getinet, Katoto Patrick Dmc, Kayode Gbenga A., Kebede Ermiyas Mulu, Kebede Hafte Kahsay, Khajuria Himanshu, Khalid Nauman, Khan Ejaz Ahmad, Khan Gulfaraz, Khatab Khaled, Kim Min Seo, Kim Yun Jin, Kisa Adnan, Kisa Sezer, Kochhar Sonali, Korshunov Vladimir Andreevich, Koul Parvaiz A., Laxminarayana Sindhura Lakshmi Koulmane, Koyanagi Ai, Krishan Kewal, Defo Barthelemy Kuate, Kumar G. Anil, Kumar Manasi, Kumar Nithin, Kwarteng Alexander, Lal Dharmesh Kumar, Landires Ivan, Lasrado Savita, Lassi Zohra S., Lazarus Jeffrey V, Lee Jane Jean-Hee, Lee Yeong Yeh, LeGrand Kate E., Lin Christine, Liu Xuefeng, Maddison Emilie R., Abd El Razek Hassan Magdy, Mahasha Phetole Walter, Majeed Azeem, Makki Alaa, Malik Ahmad Azam, Manamo Wondimu Ayele, Mansournia Mohammad Ali, Martins-Melo Francisco Rogerlandio, Masoumi Seyedeh Zahra, Memish Ziad A., Menezes Ritesh G., Mengesha Endalkachew Worku, Merie Hayimro Edemealem, Mersha Amanual Getnet, Mestrovic Tomislav, Meylakhs Peter, Mheidly Nour, Miller Ted R., Mirica Andreea, Moazen Babak, Mohammad Yousef, Mohammadi Mokhtar, Mohammed Arif, Mohammed Salahuddin, Mohammed Shafiu, Moitra Modhurima, Mokdad Ali H., Molokhia Mariam, Moni Mohammad Ali, Moradi Ghobad, Moradi Yousef, Mpundu-Kaambwa Christine, Mubarik Sumaira, Munro Sandra B., Mwanri Lillian, Nachega Jean B., Nagarajan Ahamarshan Jayaraman, Narayana Aparna Ichalangod, Naveed Muhammad, Nayak Biswa Prakash, Nduaguba Sabina O., Kandel Sandhya Neupane, Nguefack-Tsague Georges, Trang Huyen Nguyen, Nixon Molly R., Nnaji Chukwudi A., Noubiap Jean Jacques, Nunez-Samudio Virginia, Nyirenda Thomas Elliot, Oghenetega Onome Bright, Olagunju Andrew T., Olakunde Babayemi Oluwaseun, Owopetu Oluwatomi Funbi, Mahesh P. A., Padubidri Jagadish Rao, Pakhale Smita, Parekh Tarang, Kan Fatemeh Pashazadeh, Pawar Shrikant, Filipino Pepito Veincent Christian, Peprah Emmanuel K., Pinheiro Marina, Pokhrel Khem Narayan, Polibin Roman V, Pollok Richard Charles G., Postma Maarten J., Syed Zahiruddin Quazi, Radfar Amir, Radhakrishnan Raghu Anekal, Rahim Fakher, Rahimi-Movaghar Vafa, Rahimzadeh Shadi, Rahman Mosiur, Rahmani Amir Masoud, Ram Pradhum, Ranabhat Chhabi Lal, Ranasinghe Priyanga, Rao Chythra R., Rao Sowmya J., Rathi Priya, Rawaf David Laith, Rawaf Salman, Regassa Lemma Demissie, Rehman Inayat Ur, Renzaho Andre M. N., Rezaei Nima, Rezahosseini Omid, Rezai Mohammad Sadegh, Rezapour Aziz, Ripon Rezaul Karim, Rodrigues Voilet, Roshchin Denis O., Rwegerera Godfrey M., Saeed Umar, Moghaddam Sahar Saeedi, Sagar Rajesh, Saif-Ur-Rahman K. M., Salem Marwa Rashad, Samaei Mehrnoosh, Samy Abdallah M., Santric-Milicevic Milena M., Saroshe Satish, Sathian Brijesh, Satpathy Maheswar, Sawhney Monika, Schutte Aletta Elisabeth, Seylani Allen, Shaikh Masood Ali, Shaka Mohammed Feyisso, Shamshad Hina, Shamsizadeh Morteza, Shannawaz Mohammed, Shetty Adithi, Il Shin Jae, Shivakumar K. M., Singh Jasvinder A., Skryabin Valentin Yurievich, Skryabina Anna Aleksandrovna, Somayaji Ranjani, Soshnikov Sergey, Spurlock Emma Elizabeth, Stein Dan J., Sufiyan Mu'awiyyah Babale, Tadbiri Hooman, Tadesse Birkneh Tilahun, Tadesse Eyayou Girma, Tamiru Animut Tagele, Tarkang Elvis Enowbeyang, Taveira Nuno, Tekalegn Yohannes, Tesfay Fisaha Haile, Tessema Gizachew Assefa, Thapar Rekha, Tovani-Palone Marcos Roberto, Traini Eugenio, Bach Xuan Tran, Tsai Alexander C., Tusa Biruk Shalmeno, Ullah Saif, Umeokonkwo Chukwuma David, Unnikrishnan Bhaskaran, Tahbaz Sahel Valadan, Villafane Jorge Hugo, Vladimirov Sergey Konstantinovitch, Bay Vo, Vongpradith Avina, Giang Thu Vu, Waheed Yasir, Wamai Richard G., Wang Guan, Wang Yanzhong, Ward Paul, Westerman Ronny, Winkler Andrea Sylvia, Yadav Lalit, Jabbari Seyed Hossein Yahyazadeh, Yazie Taklo Simeneh, Yi Siyan, Yigit Vahit, Yirdaw Birhanu Wubale, Yonemoto Naohiro, Yu Chuanhua, Yunusa Ismaeel, Zastrozhin Mikhail Sergeevich, Zastrozhina Anasthasia, Zhang Zhi-Jiang, Zumla Alimuddin, Salomon Joshua A., Eaton Jeffrey W., Naghavi Mohsen, Dwyer-Lindgren Laura, Wang Haidong, Lim Stephen S., Hay Simon I, Murray Christopher J. L., Kyu Hmwe H.

    LANCET HIV   Vol. 8 ( 10 ) page: E633 - E651   2021.10

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  7. Less-invasive fascia-preserving surgery for abdominal wall desmoid

    Nishida Yoshihiro, Hamada Shunsuke, Sakai Tomohisa, Ito Kan, Ikuta Kunihiro, Urakawa Hiroshi, Koike Hiroshi, Imagama Shiro

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 19379   2021.9

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    The mainstay of treatment for desmoid has been shifted to active surveillance (AS). However, surgery is still being performed on abdominal wall desmoid with a wide surgical margin. The purposes of this study are to clarify the treatment results of less-invasive, fascia preserving surgery for patients with abdominal wall desmoid, and to propose a new treatment modality. Since 2009, 34 patients with abdominal desmoid have been treated in our institution. Among them, as a final treatment modality, 15 (44%) were successful with AS, 15 were subjected to less-invasive surgery, and 4 methotrexate and vinblastine treatment. The clinical results of less-invasive surgery were clarified. In the surgical group, although the surgical margin was all microscopic positive (R1), only one patient (6.7%), who has the S45F mutation type of CTNNB1, showed recurrence, at a mean follow-up of 45 months. There were no patients with familial adenomatous polyposis (FAP)-related desmoid in this cohort. Only two patients (13%) required fascia lata patch reconstruction after removal of the tumor. In patients with non FAP-related abdominal wall desmoid, less-invasive, fascia preserving surgery is recommended as a favorable option as active treatment. Based on the results of this study, multi-institutional further research is warranted with an increased number of patients.

    DOI: 10.1038/s41598-021-98775-2

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  8. Tumor location and type affect local recurrence and joint damage in tenosynovial giant cell tumor: a multi-center study

    Ota Takehiro, Nishida Yoshihiro, Ikuta Kunihiro, Tsukushi Satoshi, Yamada Kenji, Kozawa Eiji, Urakawa Hiroshi, Imagama Shiro

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 17384   2021.8

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    Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.

    DOI: 10.1038/s41598-021-96795-6

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  9. Overexpression of KIAA1199, a novel strong hyaluronidase, is a poor prognostic factor in patients with osteosarcoma

    Ito Kan, Nishida Yoshihiro, Ikuta Kunihiro, Urakawa Hiroshi, Koike Hiroshi, Sakai Tomohisa, Zhang Jiarui, Shimoyama Yoshie, Imagama Shiro

    JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH   Vol. 16 ( 1 ) page: 439   2021.7

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    Background: Hyaluronan (HA) has been shown to play important roles in the growth, invasion, and metastasis of malignant tumors. KIAA1199, which has potent HA-degrading activity, has been reported to be expressed in various malignancies and associated with patient prognosis. However, there are no reports on the expression of KIAA1199 in osteosarcoma. The aim of this study was to investigate the impact of KIAA1199 and HA expression in osteosarcoma tissues on the prognosis and other clinical characteristics of osteosarcoma patients. Methods: From 2003 to 2013, we included 49 patients with osteosarcoma at our institution, whose FFPE (formalin fixed paraffin embedded) tissue was available at the time of biopsy. The expressions of KIAA1199 and HA in each sample were assessed by immunohistochemistry using the primary antibody for KIAA1199 and HA-binding protein (HABP), respectively. For evaluation of the positivity of KIAA1199 staining, we divided the samples into two groups: High group with more than 75% positive staining and Low group with less than 75% positive staining. In the HABP staining, those with more than and less than 60% were assigned to a High group, and Low group respectively. Various clinical features were correlated with staining positivity. Prognostic factors including positivity of the staining were analyzed. Levels of mRNA expression for enzymes related to HA metabolism were assessed in two osteosarcoma cell lines using real-time RT-PCR. Results: In KIAA1199 staining, high positivity was significantly correlated with occurrence of distant metastases (P = 0.002). The necrosis rate after preoperative chemotherapy was significantly lower in the High positivity group (59%), compared to that in the Low group (84.8%) (P = 0.003). HABP positivity was not correlated with any demographic variables, although the Low positivity group had a significantly better overall survival than the High group with KIAA1199 and HABP staining (P = 0.026 and P = 0.029, respectively). In multivariable analysis, KIAA1199 (P = 0.036) and HABP staining (P = 0.002), location (P = 0.001), and distant metastasis at initial diagnosis (P < 0.001) were identified as significant prognostic factors. KIAA1199 and hyaluronan synthase mRNA were expressed at different levels in the two osteosarcoma cell lines. Conclusions: Our results showed that high expression of KIAA1199 and HA are both poor prognostic factors in osteosarcoma. KIAA1199 may be a useful marker for distant metastasis and chemoresistance.

    DOI: 10.1186/s13018-021-02590-4

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  10. Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital

    Nishida Yoshihiro, Ikuta Kunihiro, Natsume Atsushi, Ishihara Naoko, Morikawa Maki, Kidokoro Hiroyuki, Muramatsu Yukako, Nonobe Norie, Ishizuka Kanako, Takeichi Takuya, Kanbe Miki, Mizuno Seiji, Imagama Shiro, Ozaki Norio

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 11933   2021.6

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    Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

    DOI: 10.1038/s41598-021-91345-6

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  11. Short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice

    Ochiai Satoshi, Nishida Yoshihiro, Higuchi Yoshitoshi, Morita Daigo, Makida Kazuya, Seki Taisuke, Ikuta Kunihiro, Imagama Shiro

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 7875   2021.4

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    Postmenopausal osteoporosis is crucial condition that reduces the QOL of affected patients just like aged type osteoporosis. The aim of this study was to evaluate the effectiveness of short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice. Preliminary experiments identified the time of onset of osteoporosis after ovariectomy (8 weeks) in our model. We have set up a total of 4 groups (n = 8/group); vitamin D-repletion with UV irradiation (Vit.D+UV+), vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-deficiency with UV irradiation (Vit.D-UV+), vitamin D-deficiency without UV irradiation (Vit.D-UV−), and. From 8 weeks after ovariectomy, UV was irradiated for 24 weeks. At the time of 16 and 24 weeks’ irradiation, serum Vit.D levels, various markers of bone metabolism, bone mineral density, and bone strength were evaluated, and histological analyses were performed. In addition, muscle strength was analyzed. Serum 25-hydroxyvitamin D [25 (OH) D] levels at 40 and 48 weeks of age were increased in the Vit.D-UV+ group compared to the Vit.D-UV−group. Cortical thickness evaluated with micro-CT and strength of bone were significantly higher in Vit.D-UV+ group than those in Vit.D-UV− group. There was no difference in muscle strength between Vit.D-UV+ group and Vit.D-UV− group. No obvious adverse effects were observed in UV-irradiated mice including skin findings. Short-range UV irradiation may ameliorate postmenopausal osteoporosis associated with a state of vitamin D deficiency.

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  12. Limitations and benefits of FDG-PET/CT in NF1 patients with nerve sheath tumors: A cross-sectional/longitudinal study

    Nishida Yoshihiro, Ikuta Kunihiro, Ito Shinji, Urakawa Hiroshi, Sakai Tomohisa, Koike Hiroshi, Ito Kan, Imagama Shiro

    CANCER SCIENCE   Vol. 112 ( 3 ) page: 1114 - 1122   2021.3

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    The purposes of this study were to re-confirm the usefulness of PET/CT in the differentiation of benignity/malignancy of neurogenic tumors in NF1 patients, and to analyze the natural course of plexiform neurofibroma (pNF) and clarify whether PET/CT is also useful for detecting tumors other than neurogenic tumors. PET/CT was prospectively imaged in 36 NF1 patients. There were 14 malignant peripheral nerve sheath tumors (MPNSTs) in 14 patients, and 54 pNFs in 30 patients. Nine patients had both MPNST and pNF. Maximal standardized uptake value (SUVmax) was significantly higher in MPNST (median 7.6: range 4.1-10.4) (P <.001) compared with that of pNF (median 3.7: range 1.6-9.3). The cut-off value of 5.8 resulted in a sensitivity of 78.6% and specificity of 88.9%. Median age was 29 y, and median maximum tumor diameter was 82 mm in 14 MPNST patients. The 5-y overall survival rate was 46.8%. Three patients with low-grade MPNST were alive without disease at the time of this report. In 9 patients in which pNF and MPNST co-existed, 2 showed a higher SUVmax of pNF than that of MPNST. Natural history analysis of pNF (n = 43) revealed that no factors significantly correlated with increased tumor size. Nine lesions other than neurogenic tumors were detected by PET/CT including 5 thyroid lesions and 3 malignant neoplasms. This study revealed the usefulness and limitation of PET/CT for NF1 patients. In the future, it will be necessary to study how to detect over time the malignant transformation of pNF to MPNST, via an intermediate tumor.

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  13. Bone fragility of a school child during COVID-19

    Nishida Yoshihiro, Ikuta Kunihiro

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 83 ( 1 ) page: 217 - 218   2021.2

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    Osteoporosis and fragility fractures in the elderly pose a serious challenge to proper diagnosis and management during the COVID-19 outbreak.1 Therefore, it is important to advocate the care and prevention of acute and long-term fragility fractures by governments and national health service providers.2 Regarding children, acute fracture incidence has decreased during the COVID-19 pandemic, partially because of cessation of organized sports and decreased playground use.3 However, under the influence of COVID-19, there is a need to warn that children's bones might be weakened due to less sporting opportunities and less sun exposure. A 13-year-old school child was referred to our hospital from a nearby general hospital with a chief complaint of bilateral distal thigh pain of 4 weeks' duration. He had no history of systemic steroid administration for diseases. He had no history of trauma before the bilateral distal thigh pain appeared either. On the other hand, due to COVID-19, his junior high school had been closed for 3 months, with the bilateral thigh pain appearing immediately after re-starting school. At that time, he walked for about 1km to school for the first time in the three months. A magnetic resonance imaging (MRI) T2-weighted image at the time of referral to our hospital showed fractures of the distal metaphyses of the bilateral femurs. Fractures were recognized also on plain X-ray (Figure 1). The bone mineral density was decreased to 86% of the average value for the same age group, and serum 25(OH)D level was relatively low at 25 ng/ml. He had stayed indoors and been barely exposed to sunlight during the three-month closure of his school. He did not play sports when his school re-started. He was diagnosed with bilateral femoral fragility fractures possibly due to immobility and indoor life under the influence of COVID-19. He wore orthotics, performing weighted walking training, and sunbathing. In 3 months, the fractures healed, and he went to school on a full load walk.

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  14. Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma

    Yamashita Kyoko, Kohashi Kenichi, Yamada Yuichi, Akatsuka Shinya, Ikuta Kunihiro, Nishida Yoshihiro, Toyokuni Shinya, Oda Yoshinao

    GENES CHROMOSOMES & CANCER   Vol. 60 ( 1 ) page: 26 - 37   2021.1

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    Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P <.001) and poor distant metastasis-free survival (DMFS) (P <.001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.

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  15. Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: A phase II clinical trial

    Nishida Yoshihiro, Hamada Shunsuke, Urakawa Hiroshi, Ikuta Kunihiro, Sakai Tomohisa, Koike Hiroshi, Ito Kan, Emoto Ryo, Ando Yuichi, Matsui Shigeyuki

    CANCER SCIENCE   Vol. 111 ( 11 ) page: 4187 - 4194   2020.11

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    Low-dose methotrexate (MTX) plus vinblastine (VBL) chemotherapy is an effective treatment for desmoid-type fibromatosis (DF). However, previous reports have described a weekly regimen, with no reports available on a biweekly one. The aim of this study was to determine the clinical outcomes of a biweekly regimen in a cohort prospectively treated in our single institution. Since 2010, we have prospectively treated refractory DF patients with biweekly MTX (30 mg/m2) + VBL (6 mg/m2). Efficacy, progression-free survival (PFS), and correlating factors were analyzed. Adverse events (AEs) were recorded. In total, 38 patients received low-dose MTX + VBL therapy, and its efficacy was assessed in 37 of them. Nineteen (51%) patients showed partial response (PR). Clinical benefit rate was 95%. PFS at 5 y was 80.8%. In PR cases, median time to response was 10 mo. Longer duration of therapy was significantly associated with the response of PR (P =.007) by univariate analysis. There was no clear association between various clinicopathological factors, including tumor size, location, catenin beta-1 (CTNNB1) mutation status with effect. Only 3 AEs of grade 3/4 were observed. Tumor regrowth after MTX + VBL discontinuation was observed in 5 (20%) of 25 patients. Biweekly administration of MTX + VBL chemotherapy was well tolerated compared with weekly administration, and its efficacy was anticipated in DF patents, although the time needed to achieve a response may be relatively long. The treatment interval should be determined taking into account both the condition of the tumor and the patient's preference.

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  16. Forced expression of KIAA1199, a novel hyaluronidase, inhibits tumorigenicity of low-grade chondrosarcoma

    Koike Hiroshi, Nishida Yoshihiro, Shinomura Tamayuki, Zhuo Lisheng, Hamada Shunsuke, Ikuta Kunihiro, Ito Kan, Kimata Koji, Ushida Takahiro, Ishiguro Naoki

    JOURNAL OF ORTHOPAEDIC RESEARCH   Vol. 38 ( 9 ) page: 1942 - 1951   2020.9

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    Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of a novel hyaluronidase, KIAA1199, on ECM formation as well as antitumor effects on chondrosarcoma. To clarify the roles of KIAA1199 in chondrosarcoma, mouse KIAA1199 was stably transfected to Swarm rat chondrosarcoma (RCS) cells (histologically grade 1). We investigated the effects of KIAA1199 on RCS cells in vitro and an autografted model in vivo. HA binding protein (HABP) stainability and ECM formation in KIAA1199-RCS was markedly suppressed compared with that of control cells. No significant changes in messenger RNA expression of Has1, Has2, Has3, Hyal1, or Hyal2 were observed. KIAA1199 expression did not affect proliferation or apoptosis but inhibited migration and invasion of RCS cells. In contrast, the expression of KIAA1199 significantly inhibited the growth of grafted tumors and suppressed the stainability of alcian blue in tumor tissues. Although there was no direct inhibitory effect on proliferation in vitro, induction of KIAA1199 showed the antitumor effects in grafted tumor growth in vivo possibly due to changes in the tumor microenvironment such as inhibition of ECM formation. Forced expression of KIAA1199 exhibits antitumor effects on low-grade chondrosarcoma, which has chemo- and radio-therapy resistant features. Together, KIAA1199 could be a novel promising therapeutic tool for low-grade chondrosarcoma, mediated by the degradation of HA.

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  17. Low energy irradiation of narrow-range UV-LED prevents osteosarcopenia associated with vitamin D deficiency in senescence-accelerated mouse prone 6

    Makida Kazuya, Nishida Yoshihiro, Morita Daigo, Ochiai Satoshi, Higuchi Yoshitoshi, Seki Taisuke, Ikuta Kunihiro, Ishiguro Naoki

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 11892   2020.7

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    Deficiency of vitamin D is an important cause of osteosarcopenia. The purpose of this study is to examine the effects of low energy narrow-range UV-LED on osteosarcopenia in animal models of senescence-accelerated mouse prone 6 (SAMP6). Preliminary experiments specified the minimum irradiance intensity and dose efficacy for vitamin D production (316 nm, 0.16 mW/cm2, 1,000 J/m2). we set a total of 4 groups (n = 8 per group); vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-repletion with UV irradiation (Vit.D+UV +), vitamin D-deficiency without UV irradiation, (Vit.D−UV−), and vitamin D-deficiency with UV irradiation (Vit.D−UV +). Serum levels of 25(OH)D at 28 and 36 weeks of age were increased in Vit.D−UV+ group as compared with Vit.D−UV− group. Trabecular bone mineral density on micro-CT was higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. In the histological assay, fewer osteoclasts were observed in Vit.D−UV+ group than in Vit.D−UV− group. Grip strength and muscle mass were higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. Signs of severe damage induced by UV irradiation was not found in skin histology. Low energy narrow-range UV irradiation may improve osteosarcopenia associated with vitamin D deficiency in SAMP6.

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  18. Functional evaluation following deltoid muscle resection in patients with soft tissue sarcoma

    Hamada Shunsuke, Nishida Yoshihiro, Takanari Keisuke, Ota Takehiro, Urakawa Hiroshi, Ikuta Kunihiro, Sakai Tomohisa, Tsukushi Satoshi, Kamei Yuzuru, Ishiguro Naoki

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   Vol. 50 ( 7 ) page: 772 - 778   2020.7

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    Background: The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma. Methods: Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed. Results: Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P < 0.001). Conclusions: The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained.

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  19. Glomus Tumor Arising from the Surface of a Proximal Humerus : Case Report

      Vol. 55 ( 4 ) page: 385 - 388   2020.4

  20. Treatment of tenosynovial giant-cell tumour types

    Nishida Yoshihiro, Ikuta Kunihiro

    LANCET ONCOLOGY   Vol. 20 ( 8 ) page: E399 - E399   2019.8

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  21. Low-dose chemotherapy with methotrexate and vinblastine for patients with refractory desmoid tumors: A second report of relationship between efficacy and various factors.

    Nishida Yoshihiro, Sakai Tomohisa, Shimizu Koki, Urakawa Hiroshi, Arai Eisuke, Ikuta Kunihiro, Ando Yuichi, Ishiguro Naoki

    JOURNAL OF CLINICAL ONCOLOGY   Vol. 37 ( 15 )   2019.5

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  22. 後腹膜発生軟部肉腫に対する治療戦略 Reviewed

    生田国大、西田佳弘、横山幸浩、酒井智久、小池宏、今釜史郎

    整形・災害外科   Vol. 65 ( 3 ) page: 289 - 294   2022.3

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  23. 【骨・軟部腫瘍のマネジメント(その2)】類骨骨腫に対するO-armガイド下手術の有用性 Reviewed

    小池 宏、西田佳弘、生田国大、酒井智久、伊藤 鑑、今釜史郎

    別冊整形外科   Vol. 80   page: 71 - 73   2021.10

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  24. 【骨・軟部腫瘍のマネジメント(その2)】悪性骨・軟部腫瘍切除後の骨性再建における自家加温処理骨の長期成績 Reviewed

    生田国大、西田佳弘、杉浦英志、今釜史郎

    別冊整形外科   Vol. 80   page: 113 - 116   2021.10

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  25. Spontaneous Regression of Brown Tumor in a Patient Treated With Peritoneal Dialysis

    Ito Kan, Ikuta Kunihiro, Nishida Yoshihiro, Sakai Tomohisa, Imagama Shiro

    CUREUS   Vol. 13 ( 8 ) page: e17078   2021.8

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  26. 転移性骨腫瘍に対するデノスマブ長期使用により非定型大腿骨骨折を生じた1例 Reviewed

    家﨑雄介、生田国大、酒井智久、小池宏、今釜史郎、西田佳弘

    整形・災害外科   Vol. 64 ( 9 ) page: 1151 - 1154   2021.8

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  27. Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study

    Aiba Hisaki, Ikuta Kunihiro, Asanuma Kunihiro, Kawanami Katsuhisa, Tsukushi Satoshi, Matsumine Akihiko, Ishimura Daisuke, Nagano Akihito, Shido Yoji, Kozawa Eiji, Yamada Kenji, Wasa Junji, Kimura Hiroaki, Sakai Takao, Murakami Hideki, Sakai Tomohisa, Nakamura Tomoki, Nishida Yoshihiro

    CANCERS   Vol. 13 ( 15 )   2021.8

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    Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail‐like lesions. The efficacy of neoadjuvant therapy for tumors with tail‐like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail‐like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail‐like lesions during neoadjuvant therapy and histological responses. The median length of the tail‐like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail‐like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail‐like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail‐like lesions. This study indicated that the shrinkage of tail‐like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy.

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  28. 【骨・軟部腫瘍のマネジメント(その1)】診断 組織・遺伝子診断 デスモイド型線維腫症の病理組織診断におけるピットフォール CTNNB1遺伝子変異解析の有用性 Reviewed

    酒井 智久, 西田 佳弘, 生田 国大, 小池 宏, 伊藤 鑑, 今釜 史郎

    別冊整形外科   ( 79 ) page: 55 - 57   2021.4

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  29. 腹壁原発C/C-rearranged sarcomaの1例 Reviewed

    加藤 万結, 服部 浩佳, 川田 しお梨, 秋田 直洋, 関水 匡大, 小野 学, 二村 昌樹, 後藤 雅彦, 堀部 敬三, 生田 国大, 新井 英介, 西田 佳弘, 前田 尚子

    日本小児血液・がん学会雑誌   Vol. 57 ( 5 ) page: 414 - 414   2021.2

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  30. Cardiac metastases from primary myxoid liposarcoma of the thigh: a case report. International journal

    Kunihiro Ikuta, Tomohisa Sakai, Hiroshi Koike, Tohru Okada, Shiro Imagama, Yoshihiro Nishida

    World journal of surgical oncology   Vol. 18 ( 1 ) page: 227 - 227   2020.8

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    BACKGROUND: Myxoid liposarcoma is well known to have an unusual proclivity for extrapulmonary metastasis. However, cardiac metastasis of myxoid liposarcoma is very rare, even in patients with advanced disease. CASE PRESENTATION: A 40-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two years after the surgery, a low-density area in the left ventricle was found on follow-up chest computed tomography, and was suspected of being metastatic disease. He underwent surgical treatment, and the lesion was pathologically confirmed as metastasis of myxoid liposarcoma. Fifteen months later, he complained of slight dyspnea and developed metastatic disease in the right atrium. He was treated with surgical excision, followed by radiotherapy. Although there was no recurrence in the heart since the second cardiac metastasectomy, multiple metastases occurred in the abdominal cavity, lungs, and muscles. He finally died of the disease 2 years after the second cardiac metastasectomy. CONCLUSION: We experienced a case of primary myxoid liposarcoma in the thigh, accompanied by ectopic and metachronous cardiac metastases. Although this condition is rare, we should follow-up patients with myxoid liposarcoma, considering the possibility of cardiac metastasis.

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  31. Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study Reviewed

    Hiroshi Urakawa, Yuichi Ando, Tetsunari Hase, Toyone Kikumori, Eisuke Arai, Osamu Maeda, Ayako Mitsuma, Mihoko Sugishita, Tomoya Shimokata, Kunihiro Ikuta, Naoki Ishiguro, Yoshihiro Nishida

    International Journal of Cancer   Vol. 146 ( 12 ) page: 3504 - 3515   2020.6

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  32. A case of retroperitoneal dedifferentiated liposarcoma successfully treated by neoadjuvant chemotherapy and subsequent surgery

    Yokoyama Yukihiro, Nishida Yoshihiro, Ikuta Kunihiro, Nagino Masato

    SURGICAL CASE REPORTS   Vol. 6 ( 1 ) page: 105   2020.5

  33. 上腕骨近位部の骨表面に発生したグロムス腫瘍の1例 Reviewed

    杉浦 喬也, 生田 国大, 新井 英介, 酒井 智久, 小池 宏, 西田 佳弘

    臨床整形外科   Vol. 55 ( 4 ) page: 385 - 388   2020.4

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  34. Effects of ultraviolet irradiation with a LED device on bone metabolism associated with vitamin D deficiency in senescence-accelerated mouse P6

    Morita Daigo, Higuchi Yoshitoshi, Makida Kazuya, Seki Taisuke, Ikuta Kunihiro, Ishiguro Naoki, Nishida Yoshihiro

    HELIYON   Vol. 6 ( 2 ) page: e03499   2020.2

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    Aims: This study investigated effects of narrow-range ultraviolet irradiation (UVR) by a new UV–LED device on vitamin D supply and changes of bone in senescence-accelerated mouse P6 (SAMP6) with vitamin D deficiency. Main methods: We used female SAMP6 mice as a senile osteoporotic model. We set a total of 3 groups (n = 4 per group); D-UVR+ group (vitamin D deficient–dietary and UVR), D- (vitamin D deficient–dietary), and D+ groups (vitamin D contained–dietary). Mice in the D-UVR + group were UV–irradiated (305nm) with 1 kJ/m2 twice a week for 12 weeks from 20 to 32 weeks of age. Serum 25(OH)D, 1,25(OH)2D, and micro–computed tomography (CT) were assessed over time. Mechanical test, and histological assay were performed for femurs removed at 32 weeks of age. Key findings: UVR increased both serum 25(OH)D and 1,25(OH)2D levels at 4 and 8 weeks–UVR in the D-UVR+ group compared with that in the D- group (P < 0.05, respectively). Relative levels of trabecular bone mineral density in micro–CT were higher in the D-UVR+ group than in the D- group at 8 weeks–UVR (P = 0.048). The ultimate load was significantly higher in the D-UVR+ group than in the D- group (P = 0.036). In histological assay, fewer osteoclasts and less immature bone (/mature bone) could be observed in the D-UVR+ group than in the D- group, significantly. Significance: UVR may have possibility to improve bone metabolism associated with vitamin D deficiency in SAMP6 mice.

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  35. MRI characteristics predict the efficacy of meloxicam treatment in patients with desmoid-type fibromatosis Reviewed

    Shimizu Koki, Hamada Shunsuke, Sakai Tomohisa, Ito Shinji, Urakawa Hiroshi, Arai Eisuke, Ikuta Kunihiro, Koike Hiroshi, Ishiguro Naoki, Nishida Yoshihiro

    JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY   Vol. 63 ( 6 ) page: 751 - 757   2019.12

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  36. The clinical outcome of eribulin treatment in Japanese patients with advanced soft tissue sarcoma: a Tokai Musculoskeletal Oncology Consortium study Reviewed International journal

    Nakamura Tomoki, Tsukushi Satoshi, Asanuma Kunihiro, Katagiri Hirohisa, Ikuta Kunihiro, Nagano Akihito, Kozawa Eiji, Yamada Satoshi, Shido Yoji, Yamada Kenji, Kawanami Katsuhisa, Ishimura Daisuke, Sudo Akihiro, Nishida Yoshihiro

    CLINICAL & EXPERIMENTAL METASTASIS   Vol. 36 ( 4 ) page: 343 - 350   2019.8

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    The efficacy and safety of eribulin in Japanese patients with advanced soft-tissue sarcomas (STS) have not been evaluated in a large-scale cohort study. Thus, we aimed to investigate the clinical outcome of 82 Japanese patients with STS receiving eribulin across multiple study centers retrospectively. Of 82 STS patients receiving eribulin treatment, 13 were treated for locally unresectable tumor, 46 for metastasis, and 23 for both. The primary endpoint of this study was to evaluate the efficacy of eribulin against STS. The median age was 60 years. Thirty-seven were diagnosed with L-sarcoma (leiomyosarcoma or liposarcoma) and 45 had non-L-sarcoma. The median progression-free survival (PFS) for all patients was 2.7 months, with 3.4 months in those with L-sarcoma and 2.2 months in those with non-L-sarcoma. Patients with L-sarcoma showed a better PFS than those with non-L-sarcoma. Overall, the median survival time was 11.1 months, and 12.3 months and 7.9 months in patients with L-sarcoma and non-L-sarcoma, respectively; however, there was no significant differences between the groups. The prognostic significance of PS = 0 and both existence of local and metastatic STS was evaluated by multivariate analysis. We also evaluated the overall survival (OS) in patients with undifferentiated pleomorphic sarcoma (UPS) and other non-L-sarcomas. Patients with UPS had better OS than those with the other non-L-sarcomas. In conclusion, there was a significant difference in PFS between patients with L-sarcoma and non-L-sarcoma following treatment with eribulin. The anti-tumor potential of eribulin was evident in patients with UPS.

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  37. Treatment of tenosynovial giant-cell tumour types. Reviewed

    Nishida Y, Ikuta K

    The Lancet. Oncology   Vol. 20 ( 8 ) page: e399   2019.8

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    DOI: 10.1016/S1470-2045(19)30398-5

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  38. 誌上シンポジウム 骨軟部腫瘍の薬物治療アップデート 骨巨細胞腫に対するデノスマブ治療

    浦川 浩, 新井 英介, 生田 国大, 大田 剛広, 酒井 智久, 西田 佳弘

    臨床整形外科   Vol. 54 ( 7 ) page: 665 - 670   2019.7

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    DOI: 10.11477/mf.1408201410

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  39. エリブリンを用いた進行期軟部肉腫の治療成績 東海骨軟部腫瘍コンソーシアム共同研究

    中村 知樹, 筑紫 聡, 淺沼 邦洋, 片桐 浩久, 生田 国大, 永野 昭仁, 小澤 英史, 山田 聡, 紫藤 洋二, 石村 大輔, 山田 健志, 河南 勝久, 須藤 啓広, 西田 佳弘

    日本整形外科学会雑誌   Vol. 93 ( 6 ) page: S1390 - S1390   2019.6

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  40. Outpatient chemotherapy for patients with unresectable or metastatic bone sarcomas

    Urakawa Hiroshi, Nishida Yoshihiro, Mitsuma Ayako, Maeda Osamu, Sugishita Mihoko, Shimokata Tomoya, Mizutani Takeshi, Arai Eisuke, Ikuta Kunihiro, Hamada Shunsuke, Ota Takehiro, Ishiguro Naoki, Ando Yuichi

    ANNALS OF ONCOLOGY   Vol. 29   2018.10

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  41. Predictors of complications in heat-treated autograft reconstruction after intercalary resection for malignant musculoskeletal tumors of the extremity. Reviewed

    Ikuta K, Nishida Y, Sugiura H, Tsukushi S, Yamada K, Urakawa H, Arai E, Hamada S, Ishiguro N

    Journal of surgical oncology   Vol. 117 ( 7 ) page: 1469 - 1478   2018.6

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  42. Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma. Reviewed International journal

    Shunsuke Hamada, Yoshihiro Nishida, Lisheng Zhuo, Tamayuki Shinomura, Kunihiro Ikuta, Eisuke Arai, Hiroshi Koike, Koji Kimata, Takahiro Ushida, Naoki Ishiguro

    Journal of orthopaedic research : official publication of the Orthopaedic Research Society   Vol. 36 ( 6 ) page: 1573 - 1580   2018.6

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    Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of an HA synthesis inhibitor, 4-methylumbelliferone (MU), on ECM formation as well as antitumor effects in chondrosarcoma. We investigated the effects of MU on rat chondrosarcoma (RCS) cells with a grade I histological malignancy in vitro and in vivo grafted model. HA binding protein (HABP) stainability on and around the RCS cells was effectively reduced with treatment of MU. ECM formation was markedly suppressed by MU at a dose of 1.0 mM. Cell proliferation was significantly reduced by MU at 24 h. Cell motility and invasion were suppressed in a dose-dependent manner by MU. No significant changes in mRNA expression of Has1-3 were observed. Furthermore, MU inhibited the growth of grafted tumors in vivo. Histologically, chondrosarcoma cells of control tumors showed a cell-clustering structure. HABP stainability was markedly decreased in the MU-treated group. These results suggest that MU exhibits antitumor effects on low-grade chondrosarcoma, via inhibition of HA accumulation and ECM formation. MU, which is an approved drug in bile therapy, could be a new off-label medication for chondrosarcomas. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1573-1580, 2018.

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  43. Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes

    Tatematsu N., Waguri-Nagaya Y., Kawaguchi Y., Oguri Y., Ikuta K., Kobayashi M., Nozaki M., Asai K., Aoyama M., Otsuka T.

    Modern Rheumatology   Vol. 28 ( 3 ) page: 495 - 505   2018.5

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    Objectives: Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs). Methods: Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography. Results: GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression. Conclusions: Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.

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  44. 【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 軟部腫瘍の画像診療

    生田 国大, 西田 佳弘

    関節外科   Vol. 37   page: 144-152   2018.4

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  45. Single metastasis of myxoid liposarcoma from the thigh to thyroid gland: A case report Reviewed

    Hiroshi Urakawa, Kenichi Nakanishi, Eisuke Arai, Kunihiro Ikuta, Shunsuke Hamada, Takehiro Ota, Naoki Ishiguro, Yoshihiro Nishida

    World Journal of Surgical Oncology   Vol. 16 ( 1 ) page: 71   2018.3

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    Background: Thyroid metastasis of soft tissue sarcoma is very rare, and the diagnosis is especially difficult when only a single lesion is present. Case presentation: A 50-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two and a half years after the surgery, a growing low-density area was incidentally observed in the right lobe of his thyroid gland on follow-up chest computed tomography. Fine needle aspiration biopsy was performed twice, and the thyroid mass was suspected of being a sarcoma metastasis. He was treated by hemithyroidectomy, and the lesion was pathologically confirmed as a metastasis of myxoid liposarcoma. Conclusion: We experienced single thyroid gland metastasis in patients with myxoid liposarcoma in whom a growing mass is observed in the thyroid gland after radical surgery of the primary site.

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  46. Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma

    Maeta T., Ebata T., Hayashi E., Kawahara T., Mizuno S., Matsumoto N., Ohta S., Nagino M., Aoba T., Kaneoka Y., Arai T., Shimizu Y., Kiriyama M., Sakamoto E., Miyake H., Takara D., Shirai K., Ohira S., Morofuji N., Akutagawa A., Yamaguchi R., Takano M., Yamamoto H., Inoue M., Asaba Y., Watanabe T., Hashimoto M., Kawai S., Ikuta K., Matsubara H., Kato K., Kondo S.

    British Journal of Surgery   Vol. 104 ( 11 ) page: 1549 - 1557   2017.10

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    Background: Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. Methods: Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. Results: In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. Conclusion: PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection.

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  47. Immunohistochemical staining with non-phospho beta-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis Reviewed

    Tomohisa Sakai, Yoshihiro Nishida, Shunsuke Hamada, Hiroshi Koike, Kunihiro Ikuta, Takehiro Ota, Naoki Ishiguro

    DIAGNOSTIC PATHOLOGY   Vol. 12 ( 1 ) page: 66   2017.8

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    Background: Immunohistochemical staining with conventional anti-beta-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho beta-catenin antibody, which might more accurately reflect the aggressiveness of DF, in comparison to the conventional anti-beta-catenin antibody.
    Methods: Between 2003 and 2015, 40 patients with extra-peritoneal sporadic DF were prospectively treated with meloxicam or celecoxib, a COX-2 inhibitor, therapy. The efficacy of this treatment was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Immunohistochemical staining was performed on formalin-fixed material to evaluate the expression of beta-catenin and non-phospho beta-catenin, and the positivity was grouped as negative, weak, moderate, and strong. DNA was isolated from frozen tissue or formalin-fixed materials, and the CTNNB1 mutation status was determined by direct sequencing.
    Results: Of the 40 patients receiving COX-2 inhibitor treatment, there was one with complete remission, 12 with partial remission, 7 with stable disease, and 20 with progressive disease. The mutation sites in CTNNB1 were detected in 22 (55%) of the 40 cases: T41A (17 cases), S45F (3 cases), and T41I and S45P (1 each). The positive nuclear expression of non-phospho beta-catenin showed a significant correlation with positive CTNNB1 mutation status detected by Sanger method (p = 0.025), and poor outcome in COX-2 inhibitor therapy (p = 0.022). In contrast, nuclear expression of beta-catenin did not show a significant correlation with either CTNNB1 mutation status (p = 0.43) or outcome of COX-2 inhibitor therapy (p = 0.38).
    Conclusions: Nuclear expression of non-phospho beta-catenin might more appropriately reflect the biological behavior of DF, and immunohistochemical staining with non-phospho beta-catenin could serve as a more useful diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with DF.

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  48. Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model. Reviewed International journal

    Yoshitoshi Higuchi, Yoshihiro Nishida, Eiji Kozawa, Lisheng Zhuo, Eisuke Arai, Shunsuke Hamada, Daigo Morita, Kunihiro Ikuta, Koji Kimata, Takahiro Ushida, Naoki Ishiguro

    Scientific reports   Vol. 7 ( 1 ) page: 7028 - 7028   2017.8

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    The catabolism of hyaluronan in articular cartilage remains unclear. The aims of this study were to investigate the effects of hyaluronidase 2 (Hyal2) knockdown in articular cartilage on the development of osteoarthritis (OA) using genetic manipulated mice. Destabilization of the medial meniscus (DMM) model of Col2a promoter specific conditional Hyal2 knockout (Hyal -/- ) mice was established and examined. Age related and DMM induced alterations of articular cartilage of knee joint were evaluated with modified Mankin score and immunohistochemical staining of MMP-13, ADAMTS-5, KIAA11199, and biotinylated- hyaluronan binding protein staining in addition to histomorphometrical analyses. Effects of Hyal2 suppression were also analyzed using explant culture of an IL-1α induced articular cartilage degradation model. The amount and size of hyaluronan in articular cartilage were higher in Hyal2 -/- mice. Hyal2 -/- mice exhibited aggravated cartilage degradation in age-related and DMM induced mice. MMP-13 and ADAMTS-5 positive chondrocytes were significantly higher in Hyal2 -/- mice. Articular cartilage was more degraded in explant cultures obtained from Hyal2 -/- mice. Knockdown of Hyal2 in articular cartilage induced OA development and progression possibly mediated by an imbalance of HA metabolism. This suggests that Hyal2 knockdown exhibits mucopolysaccharidosis-like OA change in articular cartilage similar to Hyal1 knockdown.

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  49. 大腿骨遠位骨肉腫に対する加温処理骨と血管柄付き腓骨再建後の移植腓骨の骨癒合とサイズの変化

    中村 優, 高成 啓介, 蛯沢 克己, 神戸 未来, 中村 亮太, 亀井 譲, 生田 国大, 西田 佳弘

    日本形成外科学会会誌   Vol. 37 ( 8 ) page: 473 - 473   2017.8

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  50. Heat-stimuli-enhanced osteogenesis using clinically available biomaterials Reviewed

    Takehiro Ota, Yoshihiro Nishida, Kunihiro Ikuta, Ryuji Kato, Eiji Kozawa, Shunsuke Hamada, Tomohisa Sakai, Naoki Ishiguro

    PLOS ONE   Vol. 12 ( 7 ) page: e0181404   2017.7

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    A recent study reported that heat stress stimulates osteogenesis in an in vivo rat model using alginate gel and magnetite cationic liposomes. However, for clinical use, the efficacy for promoting osteogenesis needs to be investigated using clinically approved materials, and preferably with animals larger than rats. The aim of this study was to evaluate multiple heat stimuli-triggered osteogenesis in rat tibial defect models using already clinically applicable materials (Resovist (R) and REGENOS (R)) and determine the efficacy also in the rabbit. Fifty-eight rats and 10 rabbits were divided into two groups, respectively, with or without hyperthermia treatment at 45 degrees C for 15 min. (hyperthermia; 20 rats once a week, 8 rats three times a week, 5 rabbits once a week, control; 30 rats and 5 rabbits). Micro-CT assessment at 4 weeks revealed that a significantly stimulated osteogenesis was observed in the once a week group of both rats and rabbits as compared to the control group (p = 0.018 and 0.036, respectively). In contrast, the three times a week group did not show enhanced osteogenesis. Histological examination and image analysis showed consistent results in which the area of mineralized bone formation in the once a week hyperthermia group was significantly increased compared with that in the control group at four weeks (rat; p = 0.026, rabbit; p = 0.031). Newly formed bone was observed in the grafted materials from the periphery toward the center, and more osteoclasts were found in the once a week group. Heat stress also induced enhanced alkaline phosphatase expression in cultured osteoblastic cells, MC3T3, in vitro (p = 0.03). On the other hand, heat stress had no obvious effects on chondrogenic differentiation using ATDC5 cells. Our study demonstrates that heat-stimuli with clinically applicable novel heating materials can promote significant osteogenesis, and may thus be a promising treatment option for diseases associated with bone defects.

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  51. Recurrence after resection with curative intent for distal cholangiocarcinoma

    Komaya K., Ebata T., Shirai K., Ohira S., Morofuji N., Akutagawa A., Yamaguchi R., Nagino M., Aoba T., Kaneoka Y., Arai T., Shimizu Y., Fukami Y., Sakamoto E., Miyake H., Takara D., Tojima Y., Kawahara T., Mizuno S., Matsumoto N., Ota S., Takano M., Yamamoto H., Inoue M., Asaba Y., Watanabe T., Hashimoto M., Kawai S., Ikuta K., Matsubara H., Kondo S.

    British Journal of Surgery   Vol. 104 ( 4 ) page: 426 - 433   2017.3

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    Background: Few studies have been conducted on patterns of recurrence after resection for distal cholangiocarcinoma (DCC). The aim of this study was to investigate the incidence and pattern of recurrence after resection of DCC, and to evaluate prognostic factors for time to recurrence and recurrence-free survival (RFS). Methods: Patients who underwent pancreatoduodenectomy with curative intent for DCC between 2001 and 2010 at one of 30 hospitals in Japan were reviewed retrospectively, with special attention to recurrence patterns. The Cox proportional hazards model was used for multivariable analysis. Results: In the study interval, 389 patients underwent pancreatoduodenectomy for DCC with R0/M0 status. Recurrence developed in 213 patients (54·8 per cent). The estimated cumulative probability of recurrence was 54·3 per cent at 5 years. An initial locoregional recurrence occurred in 55 patients (14·1 per cent) and initial distant recurrence in 168 (43·2 per cent), most commonly in the liver. Isolated initial locoregional recurrence occurred in 45 patients (11·6 per cent). Independent prognostic factors for time to recurrence and RFS were perineural invasion (P = 0·001 and P = 0·009 respectively), pancreatic invasion (both P < 0·001) and lymph node metastasis (both P < 0·001). RFS worsened as the number of risk factors increased: the 5-year RFS rate was 70·6 per cent for patients without any risk factors, 50·3 per cent for patients with one factor, 31·8 per cent for those with two factors, and 13·4 per cent when three factors were present. Conclusion: More than half of patients with DCC experienced recurrence after R0 resection, usually within 5 years. Perineural invasion, pancreatic invasion and positive nodal involvement are risk factors for recurrence.

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  52. Iron overload patients with unknown etiology from national survey in Japan

    Ikuta Katsuya, Hatayama Mayumi, Addo Lynda, Toki Yasumichi, Sasaki Katsunori, Tatsumi Yasuaki, Hattori Ai, Kato Ayako, Kato Koichi, Hayashi Hisao, Suzuki Takahiro, Kobune Masayoshi, Tsutsui Miyuki, Gotoh Akihiko, Aota Yasuo, Matsuura Motoo, Hamada Yuzuru, Tokuda Takahiro, Komatsu Norio, Kohgo Yutaka

    INTERNATIONAL JOURNAL OF HEMATOLOGY   Vol. 105 ( 3 ) page: 353 - 360   2017.3

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    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

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  53. Antitumor effects of 4-methylumbelliferone, a hyaluronan synthesis inhibitor, on malignant peripheral nerve sheath tumor Reviewed

    Kunihiro Ikuta, Takehiro Ota, Lisheng Zhuo, Hiroshi Urakawa, Eiji Kozawa, Shunsuke Hamada, Koji Kimata, Naoki Ishiguro, Yoshihiro Nishida

    INTERNATIONAL JOURNAL OF CANCER   Vol. 140 ( 2 ) page: 469 - 479   2017.1

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    Hyaluronan (HA) has been shown to play important roles in the growth, invasion and metastasis of malignant tumors. Our previous study showing that high HA expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of poor patient prognosis, prompted us to speculate that inhibition of HA synthesis in MPNST might suppress the tumorigenicity. The aim of our study was to investigate the antitumor effects of 4-methylumbelliferone (MU), an HA synthesis inhibitor, on human MPNST cells and tissues. The effects of MU on HA accumulation and tumorigenicity in MPNST cells were analyzed in the presence or absence of MU in an in vitro as well as in vivo xenograft model using human MPNST cell lines, sNF96.2 (primary recurrent) and sNF02.2 (metastatic). MU significantly inhibited cell proliferation, migration and invasion in both MPNST cell lines. HA binding protein (HABP) staining, particle exclusion assay and quantification of HA revealed that MU significantly decreased HA accumulation in the cytoplasms and pericellular matrices in both MPNST cell lines. The expression levels of HA synthase2 (HAS2) and HA synthase3 (HAS3) mRNA were downregulated after treatment with MU. MU induced apoptosis of sNF96.2 cells, but not sNF02.2 cells. MU administration significantly inhibited the tumor growth of sNF96.2 cells in the mouse xenograft model. To the best of our knowledge, our study demonstrates for the first time the antitumor effects of MU on human MPNST mediated by inhibition of HA synthesis. Our results suggest that MU may be a promising agent with novel antitumor mechanisms for MPNST.

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  54. Impact of disease free status on prognosis in metastatic non-small round cell soft tissue sarcomas Reviewed

    Hiroshi Urakawa, Eiji Kozawa, Kunihiro Ikuta, Shunsuke Hamada, Naoki Ishiguro, Yoshihiro Nishida

    CLINICAL & EXPERIMENTAL METASTASIS   Vol. 33 ( 8 ) page: 799 - 807   2016.12

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    The aim of this study is to examine the impact of disease free (DF) status on the prognosis in patients with metastatic non-small round cell soft tissue sarcoma (STS). We retrospectively reviewed 51 metastatic STS patients who were treated in Nagoya University Hospital from 2005 to 2015. The relation between various clinical factors and overall survival (OS) was analyzed. The log rank test and Cox's proportional hazards test were used to evaluate the differences between groups. p-values of &lt; 0.05 were considered to indicate significance. The median follow-up period after first metastasis was 23.5 (1.6-97.1) months. There were 30 males and 21 females with a median age of 62 (15-88) years at first metastasis. The histologic subtypes were 17 undifferentiated pleomorphic sarcoma, 10 liposarcoma, 8 malignant peripheral nerve sheath tumor, and 16 others. Thirty patients had more than 2 metastases, and 15 patients had primary or local recurrent tumors. The metastatic sites were 31 lung only, 8 bone only, and 12 others. Twenty-two patients achieved DF status after surgeries and in one case proton radiotherapy for bone metastasis. DF status was marginally or significantly associated with good prognosis in patients with both pulmonary (p = 0.055) and extrapulmonary metastasis (p = 0.029). On multivariate analysis, DF status (p = 0.010) was an independent good prognostic factors for OS. In metastatic non-small round cell STS, it is an important treatment concept to achieve DF status whenever possible. This concept can apply both to pulmonary and extrapulmonary metastasis.

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  55. Short-range ultraviolet irradiation with LED device effectively increases serum levels of 25(OH)D Reviewed

    Daigo Morita, Yoshihiro Nishida, Yoshitoshi Higuchi, Taisuke Seki, Kunihiro Ikuta, Hideki Asano, Naoki Ishiguro

    JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY   Vol. 164   page: 256 - 263   2016.11

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    Impairment of the activities of daily living (ADL) by osteoporosis is an important concern in developed countries with a super-aging population. Vitamin D, which is a crucial molecule in bone metabolism and mainly produced endogenously with ultraviolet (UV) light exposure, is known to be insufficient in the elderly population. We used an UV Light-Emitting Diode (UV-LED) instrument generating a narrow-range wavelength to analyze the efficacy of endogenous vitamin D production. The primary purpose of this study was to examine the effects of UV irradiation at various narrow-range wavelengths using UV-LED on vitamin D supplementation. The second one was to clarify the short-term effects of UV irradiation on bone morphology in mice. Vitamin D-starved C57BL/6 female mice (n = 7 per group) were UV-irradiated (268 nm, 282 nm, 290 nm, 305 nm, and 316 nm) with 1 kJ/m(2) twice a week for 4 weeks. UV irradiation using UV-LED had significant effects on increasing serum 25(OH)D levels in all wavelength groups (P &lt; 0.001, all groups) as compared to a control group. Among irradiated groups, wavelength of 316 nm had a less marked effect on 25(OH)D production-compared with other wavelengths at 1 week of UV irradiation (P &lt; 0.05). Levels of 1,25(OH)(2)D were significantly increased after 4 weeks irradiation with UV-B or UV-C irradiation (P &lt; 0.05). mRNA levels of vitamin D 25-hydroxylase were increased with UV-B or UV-C irradiation (268 nm-305 nm), significantly. Micro-CT examination revealed that short-term (4 weeks) UV-irradiation did not induce morphological change of mice in any group. This study provides essential information that narrow-range UV irradiation with LED can increase the endogenous production of vitamin D, and mRNA levels of the responsible enzyme. Although bone morphology was not altered by short-term UV irradiation in this study, an increase of serum vitamin D might improve bone morphology with long-term irradiation. (C) 2016 Elsevier B.V. All rights reserved.

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  56. Simple resection of truncal desmoid tumors: A case series Reviewed

    Yoshihiro Nishida, Satoshi Tsukushi, Hiroshi Urakawa, Shunsuke Hamada, Eiji Kozawa, Kunihiro Ikuta, Naoki Ishiguro

    ONCOLOGY LETTERS   Vol. 12 ( 2 ) page: 1564 - 1568   2016.8

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    Desmoid tumors of the extra-abdominal and abdominal wall have been associated with morbidity due to the aggressive nature of cause functional impairment is desired for patients with desmoid tumors. In the present study, among patients with desmoid tumors who were prospectively and consecutively treated with identical conservative treatment with meloxicam, a selected patients of patients were treated with less invasive surgery than wide-resection. Out of 60 patients pathologically diagnosed with desmoid tumors, 9 patients with tumors refractory to conservative treatment and 4 patients who refused to receive this type of treatment were treated with planned simple resection. Subsequently, the clinical outcome of the patients and the mutational status of the catenin beta-1 (CTNNB1) gene in the tumors were analyzed. The mean age of the 13 patients that underwent planned simple resection was 39 years, and the tumors were located in the abdominal wall in 6 cases, the chest wall in 4 cases and the neck in 3 cases. All excised specimens were evaluated and positive microscopic margins were identified; however, during the mean follow-up period of 30 months, 12/13 cases, 7 of which had T41A mutations and 5 of which had no mutations (wild-type), did not develop recurrence. Only 1 initial case with an S45F mutation in the CTNNB1 gene developed recurrence. The results of the present prospectively treated with simple resection and retrospectively analyzed study suggest that planned simple resection could serve as a therapeutic modality for extraperitoneal desmoid tumors, particularly truncal ones with a wild-type or T41A mutational status.

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  57. Characteristics of cultured desmoid cells with different CTNNB1 mutation status Reviewed

    Shunsuke Hamada, Hiroshi Urakawa, Eiji Kozawa, Eisuke Arai, Kunihiro Ikuta, Tomohisa Sakai, Naoki Ishiguro, Yoshihiro Nishida

    CANCER MEDICINE   Vol. 5 ( 2 ) page: 352 - 360   2016.2

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    Desmoid tumors are benign mesenchymal neoplasms with a locally aggressive nature. The mutational status of -catenin gene (CTNNB1) is presumed to affect the tumorous activity of the cells. In this study, we isolated three kinds of desmoid cell with different CTNNB1 status, and compared their characteristics. Cells were isolated from three patients with abdominal wall desmoid during surgery, all of which were resistant to meloxicam treatment. The mutational status of the CTNNB1 exon 3 was determined for both parental tumor tissues and isolated cultured cells. -catenin expression was determined with immunohistochemistry. Responsiveness to meloxicam was investigated with MTS assay together with COX-2 immunostaining. mRNA expressions of downstream molecules of Wnt/-catenin pathway were determined with real-time RT-PCR. Three kinds of cell isolated from desmoid tumors harboring different CTNNB1 mutation status (wild type, T41A, and S45F), all exhibited a spindle shape. These isolated cells could be cultured until the 20th passage with unchanged proliferative activity. Nuclear accumulation of -catenin was observed in all cultured cells, particularly in those with S45F. Proliferating activity was significantly suppressed by meloxicam (25mol/L, P&lt;0.007) in all three cell cultures, of which parental desmoid was resistant to meloxicam clinically. The mRNA expressions of Axin2, c-Myc, and Cyclin D1 differently increased in the three cultured cell types as compared with those in human skin fibroblast cells (HDF). Inhibitors of Wnt/-catenin pathway downregulated Axin2, c-Myc, and Cyclin D1 significantly. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1.

    DOI: 10.1002/cam4.582

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  58. Low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors: relationship to CTNNB1 mutation status

    Nishida Yoshihiro, Tsukushi Satoshi, Urakawa Hiroshi, Hamada Shunsuke, Kozawa Eiji, Ikuta Kunihiro, Ando Yuichi, Ishiguro Naoki

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 20 ( 6 ) page: 1211 - 1217   2015.12

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    Background: This study was conducted to determine the efficacy and safety of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for patients with desmoid tumors refractory to meloxicam treatment, focusing in particular on the relationship between the efficacy of this chemotherapy and catenin β-1 (CTNNB1) mutation status. Patients and methods: Since March 2003, patients pathologically diagnosed with extraperitoneal desmoid tumors have been prospectively treated with meloxicam, a COX-2 inhibitor, at our institution. Patients with inoperable tumors who were resistant to meloxicam treatment underwent MTX and VBL therapy every other week. The responses of all patients were evaluated, and factors that were correlated with efficacy were analyzed, including CTNNB1 mutation status. Results: Sixty-eight patients were prospectively treated with meloxicam. MTX + VBL therapy was administered in 15 patients. Six patients showed a partial response. Only one patient presented disease progression. A few patients showed grade 3–4 treatment-related toxicity with the administration of MTX and VBL every other week. Intriguingly, CTNNB1 status did not affect the efficacy of this treatment. Conclusion: MTX and VBL treatment every other week is well tolerated and achieved a favorable response in patients resistant to meloxicam treatment, regardless of CTNNB1 mutation status.

    DOI: 10.1007/s10147-015-0829-0

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  59. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis

    Ota Takehiro, Urakawa Hiroshi, Kozawa Eiji, Ikuta Kunihiro, Hamada Shunsuke, Tsukushi Satoshi, Shimoyama Yoshie, Ishiguro Naoki, Nishida Yoshihiro

    TUMOR BIOLOGY   Vol. 36 ( 7 ) page: 5361 - 5367   2015.7

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    Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS.

    DOI: 10.1007/s13277-015-3197-5

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  60. Avian Influenza Virus Infection of Immortalized Human Respiratory Epithelial Cells Depends upon a Delicate Balance between Hemagglutinin Acid Stability and Endosomal pH

    Daidoji Tomo, Watanabe Yohei, Ibrahim Madiha S., Yasugi Mayo, Maruyama Hisataka, Masuda Taisuke, Arai Fumihito, Ohba Tomoyuki, Honda Ayae, Ikuta Kazuyoshi, Nakaya Takaaki

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 290 ( 17 ) page: 10627 - 10642   2015.4

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    The highly pathogenic avian influenza (AI) virus, H5N1, is a serious threat to public health worldwide. Both the currently circulating H5N1 and previously circulating AI viruses recognize avian-type receptors; however, only the H5N1 is highly infectious and virulent in humans. The mechanism(s) underlying this difference in infectivity remains unclear. The aim of this study was to clarify the mechanisms responsible for the difference in infectivity between the current and previously circulating strains. Primary human small airway epithelial cells (SAECs) were transformed with the SV40 large T-antigen to establish a series of clones (SAEC-Ts). These clones were then used to test the infectivity of AI strains. Human SAEC-Ts could be broadly categorized into two different types based on their susceptibility (high or low) to the viruses. SAEC-T clones were poorly susceptible to previously circulating AI but were completely susceptible to the currently circulating H5N1. The hemagglutinin (HA) of the current H5N1 virus showed greater membrane fusion activity at higher pH levels than that of previous AI viruses, resulting in broader cell tropism. Moreover, the endosomal pH was lower in high susceptibility SAEC-T clones than that in low susceptibility SAEC-T clones. Taken together, the results of this study suggest that the infectivity of AI viruses, including H5N1, depends upon a delicate balance between the acid sensitivity of the viral HA and the pH within the endosomes of the target cell. Thus, one of the mechanisms underlying H5N1 pathogenesis in humans relies on its ability to fuse efficiently with the endosomes in human airway epithelial cells.

    DOI: 10.1074/jbc.M114.611327

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  61. レックリングハウゼン病の連携診療 名大病院における神経線維腫症I型診療ネットワークの構築

    西田 佳弘, 夏目 敦至, 城所 博之, 大瀬戸 久美子, 生田 国大, 石黒 直樹, 若林 俊彦, 尾崎 紀夫

    日本レックリングハウゼン病学会雑誌   Vol. 6 ( 1 ) page: 35 - 35   2015.4

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  62. Postoperative brain metastases in soft tissue sarcomas

    Urakawa Hiroshi, Tsukushi Satoshi, Kozawa Eiji, Ikuta Kunihiro, Hamada Shunsuke, Ishiguro Naoki, Nishida Yoshihiro

    CLINICAL & EXPERIMENTAL METASTASIS   Vol. 32 ( 4 ) page: 345 - 351   2015.4

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    Brain metastases (BMs) from soft tissue sarcoma (STS) are rare but lethal. We reviewed 187 consecutive patients with STS treated with definitive surgery in Nagoya University Hospital from 2004 to 2014. There were 10 patients with neurofibromatosis-1 (NF-1). We investigated estimated brain metastasis free survival (BMFS) after surgery and overall survival (OS) after BMs in STS. The factors that affected BMFS were also investigated. Eight of 187 patients (4.3 %) developed BM with a median period of 18.2 (range 8.8–42.6) months after surgery. Seven of 8 BM patients had metastases at other sites. Estimated 5 year BMFS rate after surgery was 95.2 %, and 3 month OS rate after BM was 25.0 %. NF-1 (p < 0.0001), histological subtype of MPNST (p = 0.008), and primary tumor size ≥5 cm (p = 0.021) were significantly associated with increasing incidence of BM. In this study, postoperative BMs were common in patients with NF-1, MPNST, and large tumors. Considering the impact of NF-1 on BMFS, careful follow up for BM is necessary for NF-1 patients with metastases at other sites.

    DOI: 10.1007/s10585-015-9713-6

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  63. Prognostic impact of lymph node metastasis in distal cholangiocarcinoma

    Kiriyama M., Ebata T., Aoba T., Kaneoka Y., Arai T., Shimizu Y., Nagino M., Fukami Y., Miyake H., Sakamoto E., Takara D., Shirai K., Ohira S., Tojima Y., Hashimoto M., Akutagawa A., Yamaguchi R., Morofuji N., Kawahara T., Asaba Y., Mizuno S., Kawai S., Yamamoto H., Ikuta K., Matsubara H., Watanabe T.

    British Journal of Surgery   Vol. 102 ( 4 )   2015.3

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    Background: The aim of the study was to investigate the prognostic impact of lymph node metastasis in cholangiocarcinoma using three different classifications. Methods: Patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were included. Survival was calculated by means of the Kaplan-Meier method and differences between subgroups were assessed with the log rank test. The Cox proportional hazards model was used to identify independent predictors of survival. χ2 scores were calculated to determine the cut-off value of the number of involved nodes, lymph node ratio (LNR) and total lymph node count (TLNC) for discriminating survival. Results: Some 370 patients were included. The median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients (42.4 per cent); the median (range) number of involved nodes and LNR were 2 (1-19) and 0-11 (0.02-0.80) respectively. Four or more involved nodes was associated with a significantly shorter median survival (1.3 versus 2.2years; P = 0.001), as was a LNR of at least 0.17 (1.4 versus 2.3years; P = 0.002). Involvement of nodes along the common hepatic artery, present in 21 patients (13.4 per cent), was also associated with a shorter survival (median 1.3 versus 2.1years; P = 0.046). Multivariable analysis among 157 node-positive patients identified the number of involved nodes as an independent prognostic factor (risk ratio 1.87; P = 0.002). Conclusion: The number of involved nodes was a strong predictor of survival in patients with distal cholangiocarcinoma.

    DOI: 10.1002/bjs.9752

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  64. In vivo heat-stimulus-triggered osteogenesis

    Ikuta Kunihiro, Urakawa Hiroshi, Kozawa Eiji, Hamada Shunsuke, Ota Takehiro, Kato Ryuji, Honda Hiroyuki, Kobayashi Takeshi, Ishiguro Naoki, Nishida Yoshihiro

    INTERNATIONAL JOURNAL OF HYPERTHERMIA   Vol. 31 ( 1 ) page: 58 - 66   2015.2

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    Several studies have reported that heat stress stimulates the activity of osteoblastic cells in vitro. However, few have addressed the effects of heat stress on osteogenesis in vivo, nor have the optimal temperatures for bone formation been determined. The aim of the present study was to investigate the effects of hyperthermia treatment on osteogenesis in a rat tibial defect model. Forty-four Sprague Dawley rats were divided into two groups with or without hyperthermia treatment. A 3-mm circular defect in the proximal tibia filled with magnetite cationic liposomes embedded in alginate beads was subjected to hyperthermia treatment (4346°C). Radiological assessment at 2 weeks after the treatment showed that significantly stimulated osteogenesis was observed in the hyperthermia group as compared to the control group (p0.003). Histomorphometrical analysis at 2 weeks revealed a significant increase of newly formed bone in the hyperthermia group, compared with the control group (p<0.001). Area of newly formed bone in each hyperthermia group was significantly increased as compared with the control group (43°C; p0.005, 44°C; p0.019, 45°C; p0.003, and 46°C; p0.003, respectively). Alkaline phosphatase was overexpressed at the surfaces of newly formed bone adjacent to magnetite cationic liposome implantation. Our results demonstrate for the first time that heat stimulus accelerates osteogenesis in vivo, and may thus be of interest as a novel and promising tool to induce osteogenesis clinically as well.

    DOI: 10.3109/02656736.2014.988662

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MISC 19

  1. 骨・軟部腫瘍のマネジメント(その1) I. 総論 1. 診療体制 癌の遺伝的素因を有する患者に対する診療体制-神経線維腫症1型 Reviewed

    西田佳弘、生田国大、夏目敦至、城所博之、野々部典枝、森川真紀、尾崎紀夫

    別冊整形外科   Vol. 79   page: 13 - 17   2021.4

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  2. 肉腫の外科的治療 骨の再建 自家処理骨-パスツール処理骨- Reviewed

    杉浦英志、生田国大、中島浩敦、西田佳弘

    日本臨床   Vol. 7 ( 増刊5 ) page: 333 - 338   2020.10

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  3. LEDライトによるショートレンジ紫外線照射のvitamin D供給に有効な最小照度の検討 骨粗鬆症治療機器開発に向けての基礎研究

    牧田 和也, 西田 佳弘, 森田 大悟, 樋口 善俊, 関 泰輔, 落合 聡史, 生田 国大, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 8 ) page: S1669 - S1669   2018.8

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  4. 骨形成促進のための整形外科バイオマテリアル β-TCP配向連通多孔体を用いた骨腫瘍切除後欠損部再建の臨床成績 多施設共同前向き研究

    生田 国大, 大田 剛広, 山田 芳久, 筑紫 聡, 中島 浩敦, 山田 健志, 浦川 浩, 新井 英介, 濱田 俊介, 石黒 直樹, 西田 佳弘

    日本整形外科学会雑誌   Vol. 92 ( 8 ) page: S1932 - S1932   2018.8

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  5. デスモイド型線維腫症におけるMRIの信号強度とCTNNB1遺伝子によるメロキシカム治療反応性の予後予測解析

    清水 光樹, 濱田 俊介, 酒井 智久, 浦川 浩, 新井 英介, 生田 国大, 大田 剛広, 小池 宏, 石黒 直樹, 西田 佳弘

    日本整形外科学会雑誌   Vol. 92 ( 8 ) page: S1737 - S1737   2018.8

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  6. AYA世代高悪性度骨肉腫患者における受診の遅れと予後の検討

    浦川 浩, 新井 英介, 生田 国大, 濱田 俊介, 大田 剛広, 石黒 直樹, 西田 佳弘

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1484 - S1484   2018.6

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  7. 骨転移治療に対する院内コンセンサス形成 当院における骨転移カンファレンスの実際

    浦川 浩, 新井 英介, 満間 綾子, 前田 修, 杉下 美保子, 生田 国大, 濱田 俊介, 大田 剛広, 安藤 雄一, 石黒 直樹, 西田 佳弘

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1509 - S1509   2018.6

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  8. 軟骨芽細胞腫17例の治療成績

    清水 光樹, 西田 佳弘, 浦川 浩, 新井 英介, 生田 国大, 濱田 俊介, 大田 剛広, 酒井 智久, 小池 宏, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1580 - S1580   2018.6

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  9. 色素性絨毛結節性滑膜炎における骨軟骨破壊の発生、進行に関与する因子の検討

    大田 剛広, 西田 佳弘, 杉浦 英志, 山田 健志, 山田 芳久, 浦川 浩, 新井 英介, 生田 国大, 濱田 俊介, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1563 - S1563   2018.6

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  10. 伸長型人工膝関節と健側大腿骨骨端線抑制を併用した大腿骨遠位骨肉腫の1例

    小池 宏, 西田 佳弘, 新井 英介, 浦川 浩, 生田 国大, 濱田 俊介, 大田 剛広, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1493 - S1493   2018.6

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  11. デスモイド型線維腫症の診断におけるCTNNB1変異解析の有用性

    酒井 智久, 西田 佳弘, 濱田 俊介, 清水 光樹, 浦川 浩, 新井 英介, 生田 国大, 大田 剛広, 小池 宏, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1562 - S1562   2018.6

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  12. デスモイド型線維腫症に対する薬物治療における治療予測マーカーとしてのCTNNB1変異解析の役割

    濱田 俊介, 西田 佳弘, 酒井 智久, 浦川 浩, 新井 英介, 生田 国大, 大田 剛広, 石黒 直樹

    日本整形外科学会雑誌   Vol. 92 ( 6 ) page: S1563 - S1563   2018.6

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  13. 悪性末梢神経鞘腫瘍患者における手術成績

    生田 国大, 筑紫 聡, 浦川 浩, 小澤 英史, 濱田 俊介, 石黒 直樹, 西田 佳弘

    日本レックリングハウゼン病学会雑誌   Vol. 7 ( 1 ) page: 60-63   2016.4

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  14. Low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors: relationship to CTNNB1 mutation status. Reviewed

    Nishida Y, Tsukushi S, Urakawa H, Hamada S, Kozawa E, Ikuta K, Ando Y, Ishiguro N

    Int J Clin Oncol.   Vol. 20 ( 6 ) page: 1211-7   2015.12

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    DOI: 10.1007/s10147-015-0829-0.

  15. Expression of colony-stimulating factor 1 is associated with occurrence of osteochondral change in pigmented villonodular synovitis. Reviewed

    Ota T, Urakawa H, Kozawa E, Ikuta K, Hamada S, Tsukushi S, Shimoyama Y, Ishiguro N, Nishida Y

    Tumour Biol.   Vol. 36 ( 7 ) page: 5361-7.   2015.7

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    DOI: 10.1007/s13277-015-3197-5.

  16. Low-dose chemotherapy with methotrexate and vinblastine for Japanese patients with desmoid tumors: Relationship to CTNNB1 mutational status.

    Yoshihiro Nishida, Satoshi Tsukushi, Hiroshi Urakawa, Shunsuke Hamada, Eiji Kozawa, Kunihiro Ikuta, Yuichi Ando, Naoki Ishiguro

    JOURNAL OF CLINICAL ONCOLOGY   Vol. 33 ( 15 )   2015.5

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  17. 未成年者に生じた悪性末梢神経鞘腫瘍の検討

    生田国大, 筑紫聡, 浦川浩, 小澤英史, 濵田俊介, 石黒直樹, 西田佳弘

    日本レックリングハウゼン病学会雑誌   Vol. 6 ( 1 ) page: 68-71   2015.4

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  18. Postoperative brain metastases in soft tissue sarcomas. Reviewed

    Urakawa H, Tsukushi S, Kozawa E, Ikuta K, Hamada S, Ishiguro N, Nishida Y

    Clin Exp Metastasis.   Vol. 32 ( 4 ) page: 345-51.   2015.4

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    DOI: 10.1007/s10585-015-9713-6.

  19. In vivo heat-stimulus-triggered osteogenesis. Reviewed

    Ikuta K, Urakawa H, Kozawa E, Hamada S, Ota T, Kato R, Honda H, Kobayashi T, Ishiguro N, Nishida Y

    Int J Hyperthermia.   Vol. 31 ( 1 ) page: 58-66.   2015.2

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Presentations 10

  1. 進行性軟部肉腫に対するパゾパニブによる一次治療の成績

    生田 国大, 西田 佳弘, 酒井 智久, 小池 宏, 今釜 史郎

    第54回日本整形外科学会骨軟部腫瘍学術集会  2021.7.16  日整会

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    Event date: 2021.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:広島   Country:Japan  

  2. 骨腫瘍切除後欠損部に対するβ-TCP配向連通多孔体移植後の臨床成績 多施設前向き共同研究

    生田 国大, 大田 剛広, 筑紫 聡, 小澤 英史, 中島 浩敦, 山田 健志, 今釜 史郎, 西田 佳弘

    第94回日本整形外科学会学術総会  2021.5  日整会

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    Event date: 2021.5

    Language:Japanese   Presentation type:Poster presentation  

    Venue:オンライン   Country:Japan  

  3. 下肢原発性悪性骨腫瘍における血管柄付き腓骨移植を併用した加温処理骨再建の中長期成績

    生田 国大, 筑紫 聡, 山田 健志, 小澤 英史, 杉浦 英志, 今釜 史郎, 西田 佳弘

    第94回日本整形外科学会学術総会  2021.5  日整会

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    Event date: 2021.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:オンライン   Country:Japan  

  4. β-TCP配向連通多孔体を用いた骨腫瘍切除後欠損部再建:多施設前向き共同研究の中間成績

    生田 国大, 大田 剛広, 筑紫 聡, 小澤 英史, 山田 健志, 中島 浩敦, 濱田 俊介, 細野 幸三, 西田 佳弘

    第35回日本整形外科学会基礎学術集会  2020.10  日整会

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    Event date: 2020.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:オンライン   Country:Japan  

  5. 四肢体幹発生の脱分化型脂肪肉腫の臨床学的特徴と治療成績

    生田 国大, 西田 佳弘, 筑紫 聡, 小澤 英史, 浦川 浩, 酒井 智久, 小池 宏, 石黒 直樹

    第53回日本整形外科学会骨・軟部腫瘍学術総会  2020.9  日整会

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:オンライン   Country:Japan  

  6. 初発時切除不能であった局所進行性悪性末梢神経鞘腫瘍の治療検討

    生田 国大, 筑紫 聡, 西田 佳弘

    第11回日本レックリングハウゼン病学会学術大会  2020.2.9  日本レックリングハウゼン病学会

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    Event date: 2020.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  7. Surgical Outcomes In Elderly Patients Over 80 Years of age with soft tissue sarcomas International conference

    Kunihiro Ikuta, MD1; Yoshihiro Nishida2; Eiji Kozawa3; Satoshi Tsukushi4; Hiroshi Urakawa1; Eisuke Arai1;Tomohisa Sakai1; Hiroshi Koike1; Naoki Ishiguro1

    The CTOS 2019 Annual Meeting   2019.11  CTOS

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    Event date: 2019.11

    Language:English   Presentation type:Poster presentation  

    Venue:Tokyo   Country:Japan  

  8. 骨腫瘍切除後欠損部におけるβ-TCP配向連通多孔体の適用範囲

    生田 国大, 大田 剛広, 筑紫 聡, 小澤 英史, 中島 浩敦, 山田 健志, 浦川 浩, 新井 英介, 酒井 智久, 石黒 直樹, 西田 佳弘

    第34回⽇本整形外科学会基礎学術集会   2019.10.18  日整会

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    Event date: 2019.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

  9. 神経線維腫症1型診療ネットワークにおける整形外科腫瘍診療

    生田 国大, 西田 佳弘, 夏目 敦至, 城所 博之, 森川 真紀, 野々部 典枝, 尾崎 紀夫

    第52回⽇本整形外科学会⾻・軟部腫瘍学術集会  2019.7.12  日整会

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    Event date: 2019.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:川越   Country:Japan  

  10. 80歳以上の高齢者における軟部肉腫の手術治療成績

    生田 国大, 西田 佳弘, 小澤 英史, 筑紫 聡, 浦川 浩, 新井 英介, 大田 剛広, 酒井 智久, 石黒 直樹

    第92回日本整形外科学会学術総会  2019.5.9  日整会

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    Event date: 2019.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

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Research Project for Joint Research, Competitive Funding, etc. 1

  1. 骨軟部腫瘍領域における細胞外マトリックスを主体とした細胞外微小環境の制御による新規治療開発の研究

    2021.10 - 2022.3

    第一三共奨学寄付プログラム  がん領域

    生田国大

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    Authorship:Principal investigator  Grant type:Other

    Grant amount:\300000

KAKENHI (Grants-in-Aid for Scientific Research) 11

  1. 患者由来組織を用いた神経線維腫に対する新規治療開発:神経線維腫症1型の進行予防

    Grant number:21K09321  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(C)

    生田 国大, 西田 佳弘, 酒井 智久, 小池 宏, 伊藤 鑑

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    Authorship:Principal investigator 

    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    NF1は多発する神経線維腫を特徴とする遺伝性腫瘍症候群である。神経線維腫は疼痛、機能障害、醜状をきたし患者QOLの低下につながるが、保険診療による薬物治療は現状ない。本邦の患者数は4万人であり、神経線維腫に対する薬物治療、予防治療の開発へのニーズは高い。本研究では、NF1患者の神経線維腫に対する実現可能な新規治療法の基盤データの構築を目指す。経年的に増大、増加する全身の神経線維腫に対して、drug repositioning法により既存薬剤から腫瘍抑制効果を有する候補薬剤を同定し、神経線維腫培養細胞における薬効メカニズムの確認とpreclinical modelにおける抗腫瘍効果の評価・検討をおこなう。

  2. 細胞外マトリックス制御による悪性末梢神経鞘腫瘍に対する新規治療

    Grant number:19K16769  2019.4 - 2022.3

    科学研究費助成事業  若手研究

    生田 国大

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    Authorship:Principal investigator 

    Grant amount:\2860000 ( Direct Cost: \2200000 、 Indirect Cost:\660000 )

    本研究の目的は、MPNSTにおいて4-MUによる抗がん薬の抗腫瘍効果の増強作用について明らかにすることである。さらに、既存の抗がん薬の中から最も有望な薬剤を抽出して臨床使用に向けてのデータを蓄積することである。4-MUは利胆剤として臨床使用されており、本研究により有用なデータが得られれば早期に実現可能な治療法であると考えられる。実現可能な治療戦略の開発として本研究を行うことにより、MPNST患者の治療成績向上につなげられる。また、正常組織である細胞微小環境を制御する新規治療法の開発は、MPNSTだけでなく他のがん治療への応用も期待できる。
    悪性末梢神経鞘腫瘍(MPNST)は化学療法や通常の放射線の治療効果が不十分であり、その標準治療は手術治療のみである。研究開始して2年経過した現在でも、MPNSTに対して見込みのある新規薬剤の情報はない。本研究の目的は、悪性末梢神経鞘腫瘍(MPNST)においてヒアルロン酸合成阻害剤である4-methylumbelliferone(4-MU)による既存抗がん薬の抗腫瘍効果の増強作用を評価することで、実現可能な治療戦略を開発することである。研究実績として、令和1年度は主にin vitro実験を中心に進めた。ヒトMPNST細胞株(sNF96.2、sNF02.2)を用いて、4-MU 投与下における腫瘍細胞周囲および細胞内ヒアルロン酸の評価について、particle exclusion assay にて細胞周囲マトリクスの可視化、ELISA にて細胞内/細胞周囲/培養液中のヒアルロン酸濃度測定をおこなった。ヒアルロン酸合成酵素(HAS1-3)とヒアルロン酸受容体CD44 発現についてペルオキシダーゼ標識した抗体による細胞免疫染色とmRNA 解析にて評価した。さらに、HAS1-3 とCD44 のsiRNA によるknockdown 条件下において、腫瘍原性がどう変化するか観察するためにMTS assay、invasion assay、migration assay により評価した。また、臨床検体でのvalidityを評価するために、MPNST患者の腫瘍組織を採取して培養、継代をおこない細胞株を樹立した。令和2年度は、樹立した細胞株について同様に、上記アッセイ、解析をおこなった。ヒトMPNST細胞株による皮下移植マウスモデルの作製と生存解析、および移植腫瘍を用いたex vivo実験を令和2年度の課題としたが進捗は遅延している。
    4-MUの抗腫瘍効果について、ヒトMPNST細胞株を用いた皮下移植マウスモデル作製(in vivo)は予定通り完了している。In vitroにおいて抗がん薬の選定が済んでいないため、当面はヒトMPNST細胞株における各種抗がん薬のアッセイが優先される。遅れている理由として、MTTアッセイやアポトーシス活性をはじめとするin vitro実験では、ヒトMPNST細胞に対するダメージが臨床血中濃度を用いた場合に強く出てしまい、各種抗がん薬間の有意差を抽出できなかった。まずは細胞株に対する抗がん薬の至適濃度を同定することが急がれる。今般のCOVID19のパンデミックにより、研究計画は大きく影響を受けている。年度初めには本学ガイドラインにてCOVID19に関連する研究以外の研究活動の休止が指示され、動物実験施設への出入りも規制された。ピペットなど消耗品やPCR試薬の欠品や納入遅延も問題となった。現在は感染防止措置の上、実施可能と活動指針が緩和されたが通常とおりではない。また研究代表者は、診療従事者として、COVID対策に伴う臨床業務負担の増加に対応している。現在はICU部門でのCOVID診療応援をおこなっており、他部門との接触を回避しているため本研究には従事できていない。
    次年度においては、早急な研究再開と進展について努力する。
    有望な候補薬を抽出後に、薬剤輸送体に対する4-MU の作用の解析をin vitroでおこなう。MPNST 細胞株において、膜蛋白に存在する薬剤輸送体MDR1、MRP1、BCRPのmRNA と蛋白発現を評価する。各輸送体の抗体を用いて細胞免疫染色をおこない、抗がん薬および4-MU 投与による発現変化について評価する。抗がん薬および4-MU 投与による各輸送体のmRNAと蛋白量の変化について、リアルタイムPCR、ウェスタンブロッティングにより解析する。MPNST異種移植マウスモデルにおける腫瘍原性の評価 (in vivo)について、抗がん薬と4-MU 併用群、4-MU 投与群、抗がん薬投与群、コントロール群(vehicle)を作製し、各群における抗腫瘍効果、遠隔転移抑制、生存率曲線による生命予後を解析する。抗腫瘍効果については腫瘍重量および肺転移数の解析により局所および遠隔転移に対する効果を評価する。Ex vivo実験として、各群の異種移植腫瘍におけるヒアルロン酸、ヒアルロン酸合成酵素(HAS1-3)、薬剤輸送体蛋白発現を組織染色およびELISA(ヒアルロン酸)、mRNA(HAS1-3、薬剤輸送体蛋白)、ウェスタンブロッティング(薬剤輸送体蛋白)を評価、比較する。研究環境として、技官および研究助手の勤務制限、テレワーク解除を期待する。

  3. Fundamental research for treatment of age-associated diseases using deep-ultraviolet light emitting diode

    Grant number:17K19903  2017.6 - 2020.3

    Grant-in-Aid for Challenging Research (Exploratory)

    Nishida Yoshihiro

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    It was revealed that an LED device capable of irradiating a specific wavelength of deep ultraviolet light significantly increases blood 25 (OH) D value at a wavelength (315 nm) without side effects. The minimum illuminance / irradiation dose conditions that significantly increase blood 25 (OH) D levels (twice a week, 0.16 mW / cm2 irradiation irradiance, 1 kJ / m2 irradiation dose) were determined, and aged model mice ( Using SAM-P6 mice), we confirmed an increase in Trabecular bone mineral density and confirmed that osteoclast induction was suppressed. By using wavelength-limited LED irradiation, we were able to obtain a non-clinical POC, which is a new treatment for osteoporosis and sarcopenia.

  4. Study of novel tumor immunotherapy by modulating extracellular matrix of advanced bone and soft tissue sarcoma

    Grant number:17K10963  2017.4 - 2020.3

    URAKAWA HIROSHI

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    Authorship:Coinvestigator(s) 

    To clarify the relationship between tumor immunity and extracellular matrix / receptor / intracellular signal network mediated by hyaluronan and to establish new immunotherapy targeting in bone and soft tissue sarcoma, we evaluated the relationship between immune checkpoint molecules and hyaluronan network in bone and soft tissue sarcoma. Abundant extracellular matrix was observed in bone and soft tissue sarcoma cells, and a certain relationship between extracellular matrix/ receptor / intracellular signal network and immune checkpoint molecules was observed. Abundant expression of hyaluronan was observed in bone and soft tissue sarcoma tumor tissue, and the immune cell infiltration and immune checkpoint molecule expression were observed in certain type of sarcomas.

  5. The role of cathepsin K in the bone and lung metastases

    Grant number:15K10438  2015.4 - 2018.3

    KOZAWA EIJI

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    Authorship:Coinvestigator(s) 

    CatK synthesized by osteoclasts and/or tumor cells, tumor microenvironmental macrophage/fibroblasts to be an obvious candidate for a key enzyme involved in the destruction of bone matrix. To establish a murine bone metastasis model, a needle with syringe was used to inject MDA-MB-231 cells and Lewis lung cancer cells into the tibia of mice. Osteolytic lesions progressed markedly at tibia of mice. Scion image analysis revealed that the size of the osteolytic increased from 2 to 4 weeks. The expansion of bone lytic areas of tibia with Lewis lung cancer progressed rapidly for 2 weeks. Histological stain for bone tumor was performed.
    The sample included 50 patients with lung tumors and 19 patients with musculoskeletal tumors. The overall 5-year survival rate of the patients was 57.7%. Pre-operative MRI evaluation is helpful to determine whether tumors should be resected with adjacent bone or not.

  6. Antitumor effects of 4-Methylumbelliferone, a hyaluronan synthesis inhibitor, on malignant peripheral nerve sheath tumor

    Grant number:15K19992  2015.4 - 2018.3

    Ikuta Kunihiro

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    Authorship:Principal investigator 

    Grant amount:\3900000 ( Direct Cost: \3000000 、 Indirect Cost:\900000 )

    Hyaluronan (HA) has been shown to play important roles in the growth, invasion, and metastasis of malignant tumors. Our previous study showing that high HA expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of poor patient prognosis. The aim of this study was to investigate the antitumor effects of 4-Methylumbelliferone (MU), an HA synthesis inhibitor, on human MPNST cells and tissues.MU significantly inhibited cell proliferation, migration, and invasion in both MPNST cell lines. HABP staining, particle exclusion assay, and quantification of HA revealed that MU significantly decreased HA accumulation in the cytoplasms and pericellular matrices in both MPNST cell lines.MU administration significantly inhibited the tumor growth in the mouse xenograft model. Our results suggest that MU may be a promising agent with novel antitumor mechanisms for MPNST.

  7. Establishment of bone metastasis treatment by regulating hyaluronan network and osteoclast

    Grant number:26462261  2014.4 - 2018.3

    Urakawa Hiroshi

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    Authorship:Coinvestigator(s) 

    Bone metastases impair the quality of patients with malignancies. We focused on the co-effect of regulation of hyaluronan (HA) and bone modifying agents. We investigated the effects of 4-methylumbelliferone (MU) and/or bone modifying agents on HA expression in breast and lung cancer cell lines in addition to their tumorigenicity in vitro and in vivo. MU or zoledronic acid treatment individually suppressed proliferation, migration and invasion of breast and lung cancer cell lines, and combination treatment of MU and zoledronic acid showed synergistic effects. Combination therapy showed additive inhibitory effects on metastatic bone lesions in vivo, which paralleled the inhibition of HA accumulation by MU, and inhibition of osteoclastogenesis. These data suggest that inhibition of HA synthesis is a promising novel therapeutic candidate for bone metastasis in addition to bone modifying agents.

  8. Image-guided cryoablation for palliative therapy of skeletal metastases.

    Grant number:26462260  2014.4 - 2018.3

    Tsukushi Satoshi

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    The aim of this study was to investigate local control of in non-small round cell soft tissue sarcomas.The overall survival rates at 5 years were 85.7%.The local recurrence-free survival rates at 5 years were 89.8% (positive margin: 72.5%, margin of 2 mm or less: 60.6%). In the univariate analysis size, depth, histological grade and positive margin were significant unfavorable prognostic factors for local recurrence free survival. In multivariate analyses, we showed that positive margin and histological grade were significant independent predictors of local recurrence free survival.Positive margin and histological grade were important prognostic factors for local recurrence. Close margin (2 mm or less) in the longitudinal direction was associated with a high risk of local recurrence.The reach of the local treatment should be decided based on these factors.

  9. Establishment of a novel method for heat-stimulus induced osteogenesis using magnetite nanoparticles

    Grant number:26670659  2014.4 - 2017.3

    Yoshihiro Nishida

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    New bone formation was significantly increased by hyperthermia using magnetite cationic liposome embedded in alginate beads with an alternating magnetic field (AMF) in a rat tibial defect model. Heating materials were changed to Resovist containing ferucarbotoran and hydroxyapatite scaffold, which have been already approved in clinical use in Japan. Combination materials were grafted in tibial defect of rat and rabbit and subjected to the multiple hyperthermia in AMF. Results demonstrated that newly formed bone was observed in the grafted materials from the periphery toward the center, and more osteoclasts were found in the once a week hyperthermia group compared with non-hyperthermia group.
    Experiments of hyperthermia were performed in vitro using ATDC-5 and MC3T3 cells. Heat stress also induced enhanced alkaline phosphatase expression in cultured osteoblastic cells, MC3T3. On the other hand, heat stress had no obvious effects on chondrogenic differentiation using ATDC5 cells.

  10. Mutaion analysis for desmoid type fibromatosis and research for the establishment of a novel treatment algorithm

    Grant number:26293334  2014.4 - 2017.3

    Nishida Yoshihiro

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    CTNNB1 analyses were achieved in over 70 cases with pathologically diagnosed as desmoid-type fibromatosis (DF). Mutational status was 41A, 45F and 45P in order of descending prevalence. Relationship between CTNNB1 mutation analysis and clinical outcome of meloxicam or simple resection was determined. Based on the results of these studies, three English papers were accepted. According to the evidence of these study, treatment algorithm was established and approved by Japanese Orthopaedic Association. This algorithm is used for establishment of clinical care guideline for DF. Genome wide association study revealed that gene X is related to the clinical outcome of low dose chemotherapy for DF. APC deficient mice is obtained and subjected to the experiment for DF-development model.

  11. The role of Cathepsin K in bone metastasis and tumor progression

    Grant number:25861304  2013.4 - 2016.3

    KOZAWA Eiji

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    Authorship:Other 

    CatK synthesized by osteoclasts and/or tumor cells, tumor microenvironmental macrophage/ fibroblasts to be an obvious candidate for a key enzyme involved in the destruction of bone matrix.
    To establish a murine bone metastasis model, a needle with syringe was used to inject MDA-MB-231 cells and Lewis lung cancer cells into the tibia of mice. Osteolytic lesions progressed markedly at tibia of mice. Scion image analysis revealed that the size of the osteolytic increased from 2 to 4 weeks. The expansion of bone lytic areas of tibia with Lewis lung cancer progressed rapidly for 2 weeks. Histological stain for bone tumor was performed.
    To investigate the expression of Cathepsins, histological stain was performed on human cartilage and synovium. Increased expression of CatK in human OA cartilages/chondrocytes an synovial cells, compared with control cartilages/chondrocytes and synovial cells. Moreover, enzymatically activated CatK was also upregulated in OA chondrocytes.

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