HASHIMOTO Kazuhiko

Department of MedicineSpecially Appointed Associate Professor

Last Updated :2024/10/13

■Researcher comments

List of press-related appearances

1

■Researcher basic information

Research Keyword

  • hand surgery   osteoarthritis   oncology   

Research Field

  • Life sciences / Orthopedics

■Career

Career

  • 2024/04 - Today  近畿大学病院 整形外科 特命准教授
  • 2023/04 - Today  近畿大学病院整形外科医学部講師
  • 2022/04 - Today  くしもと町立病院整形外科・リハビリテーション科
  • 2017/04 - Today  Kindai University HospitalOrthopaedic SurgeryLecturer
  • 2018/04 - 2019/03  Mt. Sinai Hospital in TorontoOrthopaedic SurgeryResearch fellow

Educational Background

  • 2017/04 - Today  Lecturer of University
  • 2011/04 - 2017/03  assistant
  • 2007/04 - 2011/03  Kindai University Faculty of Medcine Graduate School
  • 2000/04 - 2006/03  Kindai University Faculty of Medcine

Member History

  • 2024/02 - Today   Academia Oncology   Editorial Board
  • 2022/11 - Today   Current Oncology   Reviewer Board
  • 2022/03 - Today   International Journal of Pediatrics and Child Health   Editorial Board
  • 2021/11 - Today   BMC Cancer   Editorial Board
  • 2019/04 - Today   Cancers   Reviewer Board
  • 2021/05   Molecular Medicine Reports   Editorial Board

■Research activity information

Award

  • 2024/07 近畿大学医学部 近大医学会賞
  • 2023/07 近畿大学医学部 近大医学会賞
  • 2022/07 近畿大学医学部 近大医学会賞
  • 2021/07 近畿大学医学部 近大医学会賞
     
    受賞者: 橋本和彦
  • 2019/07 近畿大学医学部 近大医学会賞
     
    受賞者: 橋本和彦
  • 2018/07 近畿大学医学部 近大医学会賞
     
    受賞者: 橋本和彦
  • 2016/07 近畿大学医学部 近大医学会賞
     
    受賞者: 橋本和彦

Paper

  • Efficacy of Surgical Intervention in Treating Pathological Fractures of the Upper Extremity: A Retrospective Case Series
    Hashimoto K. Nishimura; S. Ito; T; Kakinoki; R. Goto K
    Cureus in press 2024/10 [Refereed]
  • Bilateral atypical femur fracture in a patient with breast cancer taking zoledronic acid and denosumab: a case report
    Hashimoto K; Ito T; Yamagishi Y; Goto K
    Modern Rheumatology Case Reports in press 2024/09
  • 腎盂腎炎を伴う関節リウマチにおける横紋筋融解症の1例
    橋本和彦; 後藤公志
    整形外科 in press 2024/07 [Refereed][Invited]
  • Hashimoto K; Nishimura S; Ito T; Kakinoki R; Goto K
    Medicine(Baltimore) in press (29) e39044  2024/07 [Refereed]
     
    BACKGROUND: Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient's demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review. METHODS: A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up. RESULTS: Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome. CONCLUSION: Long-term monitoring for potential complications remains necessary.
  • Hashimoto K; Nishimura S; Ito T; Kakinoki R; Goto K
    Molecular and Clinical Oncology in press (3) 65 - 65 2024/07 [Refereed]
     
    As managing pathological fractures of the extremities can be difficult, the present study aimed to present a treatment algorithm for lower extremity bone malignancies. A total of 38 patients with impending and pathological fractures were treated at the Department of Orthopedic Surgery in Kindai University Hospital. Age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcomes, follow-up period and the MSTS scores and ECOG-PS were compared in cases of primary malignant tumors and those cases of metastatic malignant tumors were retrospectively surveyed. Post-treatment MSTS scores in cases of impending and pathological fractures were compared between intramedullary nail fixation and non-intramedullary nail fixation procedures. Disease sites included the sub-trochanteric femur in 10 patients, trochanteric femur in 8, femoral diaphysis in 7, femoral neck in 5, bilateral trochanteric femur in 3, proximal tibia in 3 and distal femur in 2 patients. A total of 10 patients had metastases between 3-20 sites. The median pre-fracture ECOG-PS score was 1. Adjuvant radiotherapy was administered to 5, chemotherapy to 8 and radiotherapy with chemotherapy to 10 patients. Surgical procedures included intramedullary nails in 18 patients, tumor arthroplasty in 4, plate fixation in 3, artificial head replacement in three, compression hip screw (CHS) in 3, conservative treatment in 2, bilateral intramedullary nail fixation in 2 and artificial bone stem with combined intramedullary nail and plate fixation, right-sided artificial head replacement and left-sided CHS in 1 patient each. The MSTS score was 19.9±8.95 for intramedullary nail fixation and 24.3±7.45 for other procedures, with a negative association between the MSTS score and pre-fracture ECOG-PS. The median follow-up period was 8 months. The outcomes were as follows: Alive with disease, 23 patients; continued disease-free, 1 patient; and dead due to disease, 14 patients. The 1-year postoperative overall survival rate was 60.5%. Moreover, the group with metastatic malignant tumors, which had significantly worse ECOG-PS, had significantly lower MSTS scores than the group with primary malignant tumors. The authors' treatment algorithm for malignant bone tumors of the lower extremity was shown to be useful.
  • Hashimoto K; Nishimura S; Shinyashiki Y; Goto K
    Cureus in press (6) e62028  2024/06 [Refereed]
     
    An eight-year-old female presenting with posterior neck pain and torticollis who had been diagnosed with coronavirus disease 2019 (COVID-19) three weeks earlier was radiographed and diagnosed with atlantoaxial rotatory fixation (AARF). Following treatment with non-steroidal anti-inflammatory drugs (NSAIDs), the posterior neck pain improved, and the torticollis was cured. Symptoms returned after two weeks, and computed tomography showed a 3.94 mm atlantodental interval and axis rotation. The patient was diagnosed with AARF relapse; symptoms resolved spontaneously prior to subsequent examination, and no further relapses were observed. This case highlights the need for clinicians to be aware that AARF may develop after COVID-19. Treatment options should be carefully considered.
  • KAZUHIKO HASHIMOTO; SHUNJI NISHIMURA; TOMOHIKO ITO; RYOSUKE KAKINOKI; GOTO KOJI
    Molecular and clinical oncology in press (1) 51 - 51 2024/05 [Refereed]
     
    A high prevalence of proximal femoral metastases persists in patients with cancer, particularly regarding lower extremity fractures. This study offers a detailed analysis of clinical characteristics of patients undergoing surgical treatment for pathological or impending fractures, enhancing treatment strategies for metastatic malignancies. A total of thirty patients who underwent treatment of impending and pathological fractures at Kindai University Hospital (Osakasayama, Japan) were included. The retrospective study comprised parameters including age, sex, fracture site, type of primary malignancy, number of metastases, pre-fracture Eastern Cooperative Oncology Group performance status (ECOG-PS) score, adjuvant therapy, treatment modality, operative time, blood loss, postoperative complications, Musculoskeletal Tumor Society (MSTS) score, outcome and follow-up period. Post-treatment MSTS scores were compared in cases of impending and pathological fractures, and between intramedullary nailing and other surgical procedures. In addition, one-year postoperative survival rates were calculated. Furthermore, operative time, blood loss and survival rates were compared between impending and pathological fractures. The participants' median age was 70.5 years, with disease sites primarily in the subtrochanteric femur, trochanteric femur, femoral diaphysis, femoral neck and other locations. Pathologies included multiple myeloma and unknown primary, lung, breast, kidney, liver, gastric, esophageal and uterine cancers. The median ECOG-PS score pre-fracture was 2. Treatment approaches involved radiotherapy, chemotherapy and a combination of both. Surgical interventions included intramedullary nailing (16 cases), endoprosthesis (1 case), bipolar head replacement (3 cases) and compression hip screw (3 cases), among others. A negative correlation (R=-0.63) existed between MSTS and pre-fracture ECOG-PS scores. The operative time was significantly shorter in impending than in pathological fractures, with impending fractures showing significantly lower blood loss. The treatment algorithm for malignant bone tumors of the lower extremity provided in the present study was efficient, potentially optimizing treatment strategies for such cases, and contributing to improved patient care and outcomes in oncology and orthopedic surgery.
  • Ryosuke Kakinoki; Yukiko Hara; Koichi Yoshimoto; Yukitoshi Kaizawa; Kazuhiko Hashimoto; Hiroki Tanaka; Takaya Kobayashi; Kazuhiro Ohtani; Takashi Noguchi; Ryosuke Ikeguchi; Masao Akagi; Koji Goto
    Bioengineering (Basel, Switzerland) 11 (4) 2024/04 
    There are many commercially available artificial nerve conduits, used mostly to repair short gaps in sensory nerves. The stages of nerve regeneration in a nerve conduit are fibrin matrix formation between the nerve stumps joined to the conduit, capillary extension and Schwann cell migration from both nerve stumps, and, finally, axon extension from the proximal nerve stump. Artificial nerves connecting transected nerve stumps with a long interstump gap should be biodegradable, soft and pliable; have the ability to maintain an intrachamber fibrin matrix structure that allows capillary invasion of the tubular lumen, inhibition of scar tissue invasion and leakage of intratubular neurochemical factors from the chamber; and be able to accommodate cells that produce neurochemical factors that promote nerve regeneration. Here, we describe current progress in the development of artificial nerve conduits and the future studies needed to create nerve conduits, the nerve regeneration of which is compatible with that of an autologous nerve graft transplanted over a long nerve gap.
  • Long-term outcomes in elderly patients with femoral neck fractures
    Nishimura S; Hashimoto K; Goto K
    Acta Medica Kindai 48 (2) 2023/12 [Refereed]
  • Kazuhiko Hashimoto; Shunji Nishimura; Yu Shinyashiki; Tomohiko Ito; Ryosuke Kakinoki; Masao Akagi
    Medicine 102 (22) e33908  2023/06 
    The involvement of New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma-associated antigen A4 (MAGE-A4) in soft-tissue sarcoma pathogenesis has recently been reported; however, their involvement in desmoid tumors (DTs) remains unknown. This study aimed to determine the involvement of NY-ESO-1 and MAGE-A4 in DTs. Immunostaining for β-catenin, NY-ESO-1, and MAGE-A4 was performed on DT biopsy specimens harvested at our institution. The positivity rate for each immune component was calculated. In addition, the correlations between the positivity rates for the immune molecules were investigated. The correlation between the positivity rate and age or longest diameter of each immune molecule was also investigated. β-catenin showed staining mainly in the tumor cell nuclei of DTs. Both NY-ESO-1 and MAGE-A4 showed staining in the nucleus, cytoplasm, and infiltrating lymphocytes of DT cells. The mean positive cell rates for β-catenin, NY-ESO-1, and MAGE-A4 were 43.9 ± 21.7, 30 ± 21.6, and 68.9 ± 20.8, respectively. A strong negative correlation was observed between β-catenin and MAGE-A4 positivity rates (r = -0.64). The positivity rates for NY-ESO-1 and MAGE-A4 showed a moderate positive correlation (r = -0.42). A very strong negative correlation was observed between age and the NY-ESO-1 positivity rate (r = -0.72). A weak negative correlation was observed between age and the MAGE-A4 positivity rate (r = -0.28). A medium negative correlation was observed between the longest tumor diameter and NY-ESO-1 positivity (r = -0.37). NY-ESO-1 and MAGE-A4 may be involved in the DT microenvironment. Thus, NY-ESO-1 and MAGE-A4 may be useful in the diagnosis of DT.
  • Aggressive intraosseous lipoma of the scapula: A rare case report
    Oka N; Hashimoto K; Shinyashiki Y; Nishimura S; Akagi M
    Experimental and Therapeutic Medicine in press 2023/06 [Refereed]
  • Takeuchi; Akihiko MD, PhD; Tsuchiya; Hiroyuki MD, PhD; Setsu, Nokitaka MD, PhD; Gokita; Tabu MD; PhD; Tome; Yasunori MD, PhD; Asano; Naofumi MD, PhD; Minami; Yusuke MD, PhD; Kawashima; Hiroyuki MD, PhD; Fukushima; Suguru MD, PhD; Takenaka; Satoshi MD, PhD; Outani; Hidetatsu MD, Ph; Nakamura; Tomoki MD, Ph; Tsukushi; Satoshi MD, Ph; Kawamoto; Teruya MD, PhD; Kidani; Teruki MD, Ph; Kito, Munehisa MD, PhD; Kobayashi; Hiroshi MD, Ph; Morii; Takeshi MD, Ph; Akiyama; Toru MD; Ph; Torigoe; Tomoaki MD, Ph; Hiraoka; Koji MD, Ph; Nagano; Akihito MD, Ph; Kakunaga; Shigeki MD, Ph; Hashimoto; Kazuhiko MD; Ph; Emori; Makoto MD; Ph; Aiba; Hisaki MD, Ph; Tanzawa; Yoshikazu MD, Ph; Ueda; Takafumi MD, PhD; Kawano; Hirotaka MD; P
    Clinical Orthopaedics and Related Research Ovid Technologies (Wolters Kluwer Health) in press (11) 2110 - 2124 0009-921X 2023/06 [Refereed]
     
    Abstract Background Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function. Questions/purposes (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function? Methods This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University. Results The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01). Conclusion This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons. Level of Evidence Level III, therapeutic study.
  • How Proximal Femur Fracture Patients Aged 65 and Older Fare in Survival and Cause of Death 5+ Years After Surgery: A Long-Term Follow-Up
    Hashimoto K; Shinyashiki Y; Ohtani K; Kakinoki R; Akagi M
    Medicine(Baltimore) in press 2023/05 [Refereed]
  • Clinicopathological assessment of PD-1/PD-L1 immune checkpoint expression in desmoid tumors
    Hashimoto K; Nishimura S; Shinyashiki Y; Ito T; Kakinoki R; Akagi M
    European journal of Histochemistry in press 2023/04 [Refereed]
  • Hashimoto K; Nishimura S; Shinyashiki Y; Ito T; Kakinoki R; Akagi M
    Medicine (Baltimore) in press (48) e31547  2022/10 
    To introduce wrapping vancomycin-containing cement around a mega-prosthesis (MP) as a novel method to prevent prosthetic joint infection after reconstruction surgery for malignant bone and soft tissue tumors. Five patients with malignant bone and soft tissue tumors treated at our hospital from April 2009 to December 2019 were included. The average age was 71.4 years. Four males and one female were included. Three patients had a bone tumor, and two had a soft tissue tumor. Three right thighs and two left femurs were affected. These tumors were identified histologically as undifferentiated pleomorphic sarcoma, spindle cell sarcoma, diffuse large cell B-cell lymphoma, metastasis of renal cancer, and metastasis of lung cancer. All patients underwent tumor resection and reconstruction with a MP. In all cases, vancomycin-containing cement (2 g/40 g) was wrapped around the implant at the extension. The average follow-up period was 30.4 months. We surveyed whether infection occurred after surgical treatment. We also investigated the Musculoskeletal Tumor Society score and clinical outcome. We observed no postoperative infection. One case of local recurrence was observed, and a hip dissection was performed. The Musculoskeletal Tumor Society score was 79.26 ± 1.26 (mean ± standard deviation) (range: 76-80.3). Three patients remained disease-free, one survived but with disease, and one died of disease. Wrapping vancomycin-containing cement around the MP may be a useful method of preventing postoperative joint infections.
  • Naohiro Oka; Kazuhiko Hashimoto; Shunji Nishimura; Osamu Maenishi; Masao Akagi
    Skeletal radiology 52 (2) 263 - 269 2022/08 
    Secondary osteosarcoma is a rare complication of primary malignancies and benign bone lesions. There are various types of diseases that cause secondary osteosarcoma. A 15-year-old male presented at our medical center complaining of pain and redness in the right lower leg. He had been diagnosed with osteofibrous dysplasia in the right tibia when he was 2 years old and since then had been followed up. Although he had a pathological fracture of the right tibia at the age of 7, his fracture healed with a plaster cast and did not require surgery. At the time of the patient's last visit, a radiograph revealed a periosteal reaction as well as erosion of the bone cortex. Magnetic resonance imaging revealed an infiltrative area in the soft tissue surrounding the osteofibrous dysplasia lesion in the tibia. Consequent to pathological examination (through bone biopsy), the patient was diagnosed with secondary osteosarcoma. The patient underwent chemotherapy and extensive resection with liquid nitrogen. He has been progressing satisfactorily after the operation. The present case is the first report of secondary osteosarcoma associated with osteofibrous dysplasia. During the long-term follow-up of osteofibrous dysplasia, oncologists should be aware of the possibility of secondary osteosarcoma.
  • Hashimoto K; Nishimura S; Shinyashiki Y; Ito T; Akagi M
    Medicine(Baltimore) in press (39) e30688  2022/08 [Refereed]
     
    The prognosis for soft tissue sarcomas (STSs) is poor, especially for highly aggressive STSs, and the details of prognostic factors are unknown. This study aimed to investigate the prognostic factors for STSs in hematologic inflammatory markers. We included 22 patients with STSs treated at our institution. The STSs were histologically classified as follows: undifferentiated pleomorphic sarcoma, 7 cases; myxofibrosarcoma, 6 cases; and malignant peripheral nerve sheath tumor, 2 cases. The average patient age was 72.06 years. The numbers of patients who underwent each procedure were as follows: wide resection, 7; wide resection and flap, 2; marginal resection, 2; wide resection and radiation, 1; additional wide resection with flap, 1; wide resection and skin graft, 1; and radiotherapy only, 1. The median follow-up period was 26 months (3-92 months). The outcomes were as follows: continuous disease free, 6 cases; no evidence of disease, 6 cases; alive with disease, 1 case; and died of disease, 2 cases. Pretreatment blood examinations for C-reactive protein (CRP) and albumin levels; neutrophil, lymphocyte, and white blood cell (WBC) counts; and neutrophil/lymphocyte (N/L) ratio were investigated and correlated with tumor size, tissue grade, and maximum standardized uptake value (SUVmax). CRP level and neutrophil and WBC counts were positively correlated with tissue grade and SUVmax. N/L ratio was positively correlated with tumor size and SUVmax. CRP level, WBC and neutrophil counts, and N/L ratio may be poor prognostic factors for highly aggressive STSs.
  • Kazuhiko Hashimoto; Shunji Nishimura; Tomohiko Ito; Masao Akagi
    Medicine 101 (22) e29471  2022/06 
    INTRODUCTION: A giant cell tumor of soft tissue (GCST) is a benign soft tissue tumor that often occurs subcutaneously in the extremities. Rare cases of malignant GCST have been reported, but its pathogenesis remains unclear. PATIENTS CONCERNS: We report a case of a 68-year-old man who noticed a painless mass on his second toe one and a half years ago. He visited the Department of Dermatology at our hospital. Magnetic resonance imaging revealed a soft tissue tumor, surrounding the distal aspect of the second toe. DIAGNOSIS: A biopsy of the tumor was performed by a dermatologist, and it revealed a malignant giant cell tumor of the toe. INTERVENTIONS: He was referred to our department and underwent lay amputation for wide-margin resection. OUTCOMES: No recurrence or metastasis was observed 5 years after treatment. CONCLUSION: : Malignant GCST should be treated with wide-margin resection immediately after its diagnosis.
  • Hashimoto K; Nishimura S; Ito T; Oka N; Kakinoki R; Akagi M
    European journal of Histochemistry in press (3) 2022/06 [Refereed]
     
    The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.
  • 柿木 良介; 田中 寛樹; 原 佑紀子; 橋本 和彦; 大谷 和裕; 赤木 將男; 貝澤 幸俊; 淘江 宏文; 池口 良輔
    日本整形外科学会雑誌 (公社)日本整形外科学会 96 (5) 427 - 435 0021-5325 2022/05
  • Hashimoto K; Nishimura S; Shinyashiki Y; Ito T; Tanaka H; Ohtani K; Kakinoki R; Akagi M
    Medicine(Baltimore) in press (28) e29621  2022/05 [Refereed]
     
    RATIONALE: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4. PATIENT CONCERNS: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed. DIAGNOSIS: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels. INTERVENTIONS: An excision was performed from the base of the thumb to achieve a wide margin. OUTCOMES: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications. LESSONS: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.
  • Hashimoto K; Nishimura S; Miyamoto H; Toriumi K; Ikeda T; Akagi M
    Medicine(Baltimore) in press (32) e29963  2022/04 [Refereed]
     
    There is no consensus on a treatment strategy for spinal giant cell tumor of bone (GCTB) because of the difficulty in their treatment. Treatment options often include the use of the controversial denosumab, an antibody therapy aimed at tumor shrinkage, different curettage techniques, resection, or a combination of these therapies. The current study aimed to identify treatment methods associated with favorable outcomes in patients with spinal GCTB. We retrospectively reviewed 5 patients with spinal GCTB, including patients with tumors of the sacrum, treated at our hospital between September 2011 and November 2020. Two men and 3 women were included in the study. The median follow-up period was 74 months (range: 14-108 months). We surveyed the tumor site, treatment method, denosumab use, and outcomes. The median age was 17 years (range: 17-42 years). There were 2 cases of sacral GCTB and 1 case each of lumbar, cervical, and thoracic vertebral GCTB. The comorbidities observed included hepatitis, malignant lymphoma, atopic dermatitis, and asthma. The treatment method included zoledronic acid after embolization and denosumab, denosumab only, curettage and posterior fusion, and curettage resection after embolization and anterior and posterior fusion. Denosumab was used in all cases. Three patients were continuously disease-free, 1 patient with no evidence of disease, and 1 patient alive with disease. Aggressive treatment, especially surgical treatment, may lead to good results in spinal GCTB.
  • Hashimoto K; Nishimura S; Ito T; Kakinoki R; Akagi M
    European journal of Histochemistry in press (2) 2022/04 [Refereed]
     
    Immunotherapy has altered the treatment paradigm for soft tissue sarcomas (STSs). Considering the limited information regarding the clinical significance of immunohistochemical markers in STS, the purpose of this study was to determine the clinical significance of programmed cell death-1 (PD-1), PD ligand-1 (PD-L1), New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and melanoma-associated antigen-A4 (MAGE-A4) expression in STSs. Twenty-two patients (median age, 72.5 years) with STSs treated at our hospital were included in this study. The specimens obtained at the time of biopsy were used to perform immunostaining for PD-1, PD-L1, NY-ESO, and MAGE-A4. The rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells and cases were calculated. The correlations among the positive cell rates of the immunohistochemical markers as well as their correlations with the histological grade, tumor size, or maximum standardized uptake (SUVmax) value were also determined. The average rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells were 4.39%, 28.0%, 18.2%, and 39.4%, respectively. Although the PD-1-positive cell rate showed no correlation with the rates of NY-ESO-1- and MAGE-A4-positive cells, the PD-L1-positive cell rates showed strong positive correlations with the rates of NY-ESO-1- and MAGE-A4-positive cells. PD-1-, PD-L1-, NY-ESO-1-, and MAGE-A4-positive cell rates showed weak to moderate correlations with histological grade or tumor size, while the PD-1-, PD-L1-, and MAGE-A4-positive cell rates showed strong to very strong positive correlations with the SUVmax value. Thus, PD-1, PD-L1, NY-ESO, and MAGE-A4 expressions are correlated and may be involved in the aggressive elements of STSs.
  • Kazuhiko Hashimoto; Shunji Nishimura; Tomohiko Ito; Masao Akagi
    Diagnostics (Basel, Switzerland) 12 (3) 2022/03 
    We aimed to investigate the clinical significance of the expression of NY-ESO-1 and MAGE-A4 in soft tissue sarcoma (STS). Immunostaining for NY-ESO-1, MAGE-A4, and Ki67 was performed using pathological specimens harvested from 10 undifferentiated pleomorphic sarcoma (UPS), nine myxofibrosarcoma (MFS), and three malignant peripheral nerve sheath tumor (MPNST) patients treated at our hospital. We examined the correlation of NY-ESO-1 and MAGE-A4 expression levels with tumor size, histological grade, and SUVmax values. Positive cell rates of various markers were also compared between patients in remission and those who were not in remission. The rates of cases positive for NY-ESO, MAGE-A4, and Ki67 were 50%, 63.6%, and 90.9%, respectively. The average rates of cells positive for NY-ESO, MAGE-A4, and Ki67 in all STS types were 18.2%, 39.4%, and 16.8%, respectively. A positive correlation was observed between rates of cells positive for NY-ESO-1 and MAGE-A4 and between NY-ESO-1 and MAGE-A4 expression levels and clinical features. There was no significant difference in the positive cell rate of NY-ESO-1 or MAGE-A4 between remission and non-remission cases. Our results suggest that NY-ESO-1 and MAGE-A4 expression may be useful for the diagnosis and prognostication of UPS, MFS, and MPNST.
  • Kazuhiko Hashimoto; Shunji Nishimura; Seiichiro Mitani; Tomohiko Ito; Masao Akagi
    Skeletal radiology 2022/03 
    Myxoid liposarcoma (MLPS) is known to have a variety of metastatic manifestations. We report a MLPS originating in the pelvis with metastasis to the calcaneus. The patient was a 72-year-old man who developed lumbar pain and right lower extremity pain 2 years ago. He visited a nearby clinic and underwent a radiographic examination. Computed tomography (CT) revealed a tumor in the right retroperitoneum. A CT-guided needle biopsy was performed, and pathological examination revealed myxoid liposarcoma. Wide surgical resection was not performed due to the patients' wishes, technical difficulties, and magnitude of the invasion, and the patient received heavy particle radiation therapy (HPRT) of 70.4 Gy. After HPRT, the tumor mass was slightly reduced. However, 11 months after HPRT, a recurrent lesion in the liver was observed. Although HPRT was performed again for the metastatic liver lesion (70.4 Gy), the tumor increased in size. Furthermore, 1 month later, the patient complained of pain in the left foot, and CT and magnetic resonance imaging revealed an osteolytic lesion in the calcaneus. A biopsy was performed, and pathological examination showed a metastatic lesion of myxoid-type liposarcoma. The patient wore a short lower limb orthosis and was able to walk but died 1 month later. Oncologists should note that MLPS can metastasize to the calcaneus.
  • Hashimoto K; Nishimura S; Sakata N; Inoue M; Sawada A; Akagi M
    Medicine(Baltimore) in press (43) e27650  2021/10 [Refereed]
     
    ABSTRACT: Recent data suggest that programmed cell death -1 (PD-1) and programmed cell death ligand-1 (PD-L1) are involved in the pathogenesis of Langerhans cell histiocytoma (LCH); however, their contributions are not well established. Also, the involvement of PD-1/PD-L1 molecules in musculoskeletal LCH remains particularly unclear. The current study aims to characterize the involvement of PD-1/PD-L1 immune checkpoint system in the pathogenesis of musculoskeletal LCH. PD-1/PD-L1 expression was evaluated in 6 patients, 3 men and 3 women with a mean age of 13.5 years, with musculoskeletal LCH who were treated at Kindai University Hospital and Osaka Women's and Children's Hospital between November 2005 and December 2020. The median follow-up period for all patients with musculoskeletal LCH was 41 months. We surveyed symptoms, number of lesions, treatment modality, and outcomes. Immunostaining for CD4, CD8, PD-1, and PD-L1 was also performed on pathological specimens obtained by biopsy. Multiple lesions were observed in 5 cases, and a single lesion was observed in 1 case. The chief complaint in 5 cases was pain. Four patients underwent spontaneous regression. The other 2 patients received chemotherapy. The outcomes included continuous disease-free (n = 5) and alive with the disease (n = 1). The CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 100%, 100%, 16.6%, and 83.3%, respectively. The CD4/PD-L1, CD8/PD-L1, and PD-1/PD-L1 positive rates in all the specimens were 83.3%, 83.3%, and 16.6%, respectively. We believe that the PD-1/PD-L1 immune checkpoint molecules may play some role in the microenvironment of musculoskeletal LCH.
  • Inoue S; Hashimoto K; Yamagishi K; Moritake A; Nakagawa K; Akagi M
    International Journal of Surgery Case Reports Elsevier BV in press 106483 - 106483 2210-2612 2021/10
  • Kazuhiko Hashimoto; Shunji Nishimura; Tomohiko Ito; Masao Akagi
    European journal of histochemistry : EJH 65 (3) 2021/07 [Refereed]
     
    Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.
  • Limitations and Usefulness of Biopsy Techniques for the Diagnosis of Metastatic Bone and Soft Tissue Tumors
    Hashimoto K; Nishimura S; Ito T; Oka N; Akagi M
    Annals of Medicine Surgery in press 2021/07 [Refereed]
  • 橋本 和彦; 西村 俊司; 石澤 命彦; 伊藤 智彦; 岡 尚宏; 赤木 將男
    日本整形外科学会雑誌 (公社)日本整形外科学会 95 (6) S1411 - S1411 0021-5325 2021/06
  • Kazuhiko Hashimoto; Shunji Nishimura; Naoki Sakata; Masami Inoue; Akihisa Sawada; Masao Akagi
    Medicina (Kaunas, Lithuania) 57 (4) 2021/04 
    Background and Objectives: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. Materials and Methods: We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. Results: The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. Conclusion: LCH should be diagnosed as early as possible to treat it appropriately.
  • Kazuhiko Hashimoto; Shunji Nishimura; Masao Akagi
    Medicina (Kaunas, Lithuania) 57 (2) 2021/02 [Refereed]
     
    Background: Metastasis to soft tissue is rare, and the pathogenesis remains unclear. Soft tissue metastases (STMs) have varied presentations; existing reports are few. Herein, we report a case of STMs of the shoulder with a rich characterization. Case presentation: A 93-year-old man presented to our hospital with pain and swelling of the left shoulder for one week. Magnetic resonance imaging (MRI) showed a T1 low-intensity and T2 high-intensity mass. We suspected a primary sarcoma and performed a needle biopsy. However, on histopathological examination, the findings were suggestive of lung adenocarcinoma. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography also revealed FDG accumulation in the right lung, thus confirming the diagnosis. Conclusion: Oncologists should keep in mind that STMs of lung cancer may resemble soft-tissue sarcomas at the time of initial diagnosis.
  • Kazuhiko Hashimoto; Shunji Nishimura; Tomohiko Ito; Naohiro Oka; Masao Akagi
    Medicina (Kaunas, Lithuania) 57 (2) 2021/02 [Refereed]
     
    Undifferentiated pleomorphic sarcoma (UPS) is major type of soft tissue sarcomas. UPS presenting with inflammation is rare, and its pathophysiology remains unclear. Herein, we report a rare case of UPS with prolonged fever. A 91-year-old female complaining of high fever was referred to our hospital because of a high C-reactive protein (CRP) level of 12.51 mg/dL. She had been experiencing intermittent fevers for approximately 10 years. The fever of unknown origin worsened with time and went into remission with repeated antimicrobial therapy. She also had a mass on her central lower back over the sacral region for 6 years, which showed a gradual increase in size. The blood tests showed that the leukocyte count and neutrophils were 6.51 × 103 /µL and 70.3%, respectively. She had a 10 × 10 cm mass on her buttock that showed 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) accumulation on FDG-positron emission tomography-computed tomography examination (standardized uptake value-max value: 5.4). A blood culture examination was performed to rule out bacteremia, however, no bacteria were identified. We then performed a needle biopsy and confirmed the diagnosis of UPS; subsequently, the patient underwent a wide-margin resection. A few days after the surgery, her CRP, leukocyte, and neutrophil levels decreased to 0.305 mg/dL, 2.83 × 103/uL, and 50.1%, respectively. This case demonstrated that UPS with inflammation should be treated surgically as soon as possible after ruling out other sources of infection to achieve a favorable prognosis.
  • Kazuhiko Hashimoto; Shunji Nishimura; Takaaki Chikugo; Ryosuke Kakinoki; Masao Akagi
    Acta medica Okayama 74 (6) 531 - 535 2020/12 [Refereed]
     
    Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma.
  • Kazuhiko Hashimoto; Shunji Nishimura; Daichi Matsumura; Kazuhiro Ohtani; Masao Akagi
    The Tohoku journal of experimental medicine 251 (4) 273 - 277 2020/08 [Refereed]
     
    Salmonella infection predominantly causes four clinical syndromes: enteric fever, gastroenteritis, bacteremia, and asymptomatic carrier state. Salmonella osteomyelitis is an extremely rare manifestation of salmonella infection except in children with hemoglobinopathies. Salmonella osteomyelitis has been reported to mostly affect the diaphysis of long bones and lumbar spine. Here, we describe a case of salmonella osteomyelitis of the right 6th rib in a 74-year-old woman who presented with breast pain, swelling, high fever and local heat. Her medical history showed myocardial infarction; namely, at the age of 71, the patient had undergone the drug-eluting stent placement in the left anterior descending artery. A computed tomography (CT) scan at the first visit to another hospital showed a mass in the chest that invaded the ribs. 18F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging showed a lesion suspected to be a mammary malignant tumor. A needle biopsy revealed mesenchymal cells and suspected mammary sarcoma. However, the osteomyelitis of the rib was diagnosed when pyogenic tissue was observed during an open biopsy. The bacterial culture examination identified Salmonella enterica. Surgical drainage and antibiotic treatment were performed. Importantly, there was no evidence for any underlying disease that could lead to an immunocompromised status of the patient. To our knowledge, this is the first report of salmonella osteomyelitis of the rib presenting in an older female that required differentiation from a mammary tumor. Clinicians should consider rib osteomyelitis when they find swelling and local heat in the female's breast tissue and detect no cancerous tissue.
  • Kazuhiko Hashimoto; Shunji Nishimura; Masao Akagi
    Diagnostics (Basel, Switzerland) 10 (8) 2020/07 [Refereed]
     
    Recent data have suggested that PD-1 and PD-L1 are involved in osteosarcoma (OS) pathogenesis; however, their contributions are not well-established. Here, the PD-1/PD-L1 expression was evaluated in (OS) cases. Preoperative needle biopsy specimens were obtained from 16 patients with OS. Immunostaining for CD4, CD8, PD-1, and PD-L1 was performed on pathological specimens. Clinical parameters, including age, tumor size, preoperative alkaline phosphatase (ALP) level, standardized uptake value (SUV)-max level, and survival rate, were compared between PD-1/PD-L1-positive and -negative groups. CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 75%, 75%, 18.7%, and 62.5%, respectively. The rates of co-expression of CD4 and CD8 with PD-L1 were 56.2% and 50%, respectively. Tumors were significantly larger in PD-L1-negative cases than in PD-L1-positive cases. Age, size and ALP and SUV-max levels did not differ significantly between PD-1/PD-L1-positive and -negative cases. The 3-year survival rates did not differ significantly between PD-1-positive and -negative cases or between PD-L1-positive and -negative cases. However, the occurrence of cancer-related events, including recurrence, metastasis, and death was associated with the PD-1-negative and PD-L1-positive status. The PD-1/PD-L1 checkpoint is likely involved in the immune microenvironment in OS and may be involved in the occurrence of cancer-related events.
  • Kazuhiko Hashimoto; Masao Akagi
    The Journal of international medical research 48 (6) 300060520931609 - 300060520931609 2020/06 [Refereed]
     
    Osteoarthritis (OA) is a chronic joint disorder that causes degeneration of cartilage, synovial inflammation, and formation of osteophytes. Aging, obesity, and sex are considered the main risk factors of OA. Recent studies have suggested that metabolic syndrome (MetS) disorders, such as hypertension, hyperlipidemia, diabetes mellitus, and obesity, may be involved in the pathogenesis and progression of OA. MetS disorders are common diseases that also result in atherosclerosis. Researchers believe that OA and atherosclerosis have underlying similar molecular mechanisms because the prevalence of both diseases increases with age. Oxidation of low-density lipoprotein (ox-LDL) is believed to play a role in the pathogenesis of atherosclerosis. Recent reports have shown that ox-LDL and low-density lipoprotein receptor 1 (LOX-1) are involved in the pathogenesis of OA. The purpose of this narrative review is to summarize the current understanding of the role of the LOX-1/ox-LDL system in the pathogenesis of OA and to reveal common underlying molecular pathways that are shared by MetS in OA and the LOX-1/ox-LDL system.
  • Kazuhiko Hashimoto; Shunji Nishimura; Naohiro Oka; Masao Akagi
    BMC research notes 13 (1) 257 - 257 2020/05 [Refereed]
     
    OBJECTIVE: To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases. RESULTS: The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0 ≥ surgical margin are essential.
  • 転移性肋骨骨腫瘍の治療経験
    橋本 和彦; 西村 俊司; 森下 貴文; 岡 尚宏; 赤木 將男
    中部日本整形外科災害外科学会雑誌 (一社)中部日本整形外科災害外科学会 63 (春季学会) 82 - 82 0008-9443 2020/04
  • Kazuhiko Hashimoto; Shunji Nishimura; Naohiro Oka; Masao Akagi
    Molecular and clinical oncology SPANDIDOS PUBL LTD 12 (4) 358 - 364 2049-9450 2020/04 [Refereed]
     
    The aim of the present study was to investigate the clinical outcomes of adolescents and young adults with bone and soft tissue sarcomas. Records of seven male and six female patients aged 17-39 years with bone or soft tissue sarcomas were reviewed retrospectively; data on histology, size, location, grade/stage, treatment, recurrence, presence of metastasis, and prognosis were retrieved. Five-year survival rates were estimated using the Kaplan-Meier method and were compared according to age, sarcoma type, histological grade, and location. Seven and six patients had bone and soft tissue sarcomas, respectively. In terms of histology, patients with bone sarcomas included four with osteosarcoma, two with chondrosarcoma, and one with Ewing sarcoma of the bone. Of those with soft tissue sarcomas, three had liposarcomas, two had synovial sarcomas, and one each had Ewing sarcoma and leiomyosarcoma. The five-year survival rate of the cohort was 57.1%. Younger patients with sarcoma had poorer survival than older patients. Patients with high-grade sarcomas also had poorer survival than those with low-grade tumors. In addition, patients with trunk-located tumors had poorer survival than those with tumors in the extremities. These findings suggest that, younger adolescents and young adults with high-grade or trunk-located sarcomas require more aggressive treatment.
  • Kazuhiko Hashimoto; Shunji Nishimura; Koutaro Yamagishi; Ichiro Tsukamoto; Koichi Nakagawa; Shinji Inoue; Shigeki Asada; Ryosuke Kakinoki; Masao Akagi
    Molecular and clinical oncology 12 (4) 355 - 357 2020/04 [Refereed]
     
    Synovial osteochondroma (SO) is a relatively uncommon tumor affecting the synovial joints that is characterized by the development of hyaline cartilage from the synovial membrane. The basic pathophysiology of SO is thought to be the metaplastic change of the synovium to hyaline cartilage. Large extra- or para-articular lesions in the Hoffa's fat pad are relatively uncommon. A 56-year-old woman complained of knee pain associated with a large lesion on the anterior of the right knee. She also had restricted range of motion in the knee. Examination revealed an elastic hard 8x9-cm lesion involving the patellar tendon. Computed tomography and magnetic resonance imaging demonstrated a mosaic-intensity mass lesion in the inferior side of the Hoffa's fat pad as well as the patellar tendon. The patient underwent needle biopsy. Histological analysis revealed a solitary SO. There were no atypical features suggestive of malignancy and the mass was resected marginally. The patient had no recurrence or knee functional disorder 3 years postoperatively. There are no reports of SO involving the patellar tendon with restriction of range of motion. Removal of the mass lesion for management for SO, as in the present case, is unusual. To the best of our knowledge, this is the first case of extra-articular SO in the Hoffa's fat pad involving the patellar tendon causing a restriction of range of motion of the knee. Marginal surgical resection improved knee function.
  • Shintaro Iwata; Akira Kawai; Takafumi Ueda; Takeshi Ishii; Tsukasa Yonemoto; Hiroto Kamoda; Yoshihisa Suzuki; Kazutaka Kikuta; Jungo Imanishi; Taketo Okubo; Yasuo Yazawa; Tsukasa Sotobori; Hiroaki Murata; Toshifumi Ozaki; Toshiyuki Kunisada; Tomohiro Fujiwara; Shigeki Kakunaga; Koji Hiraoka; Tetsuya Hamada; Kotaro Matsuda; Takashi Yanagawa; Kenichi Saito; Hirofumi Namba; Motohiro Kawasaki; Shunji Nishimura; Kazuhiko Hashimoto; Takeshi Okamoto; Ukei Anazawa; Itsuo Watanabe; Michiyuki Hakozaki; Yoshinori Imura; Yoshinori Imura; Eisuke Kobayashi; Koichi Ogura; Taketoshi Yasuda; Kayo Suzuki; Toru Akiyama; Masami Hosaka; Munenori Watanuki; Kou Hayashi; Toshiharu Shirai; Ryu Terauchi; Hisaki Aiba; Hiroaki Kimura; Kunihiro Asanuma; Tomoki Nakamura; Tomohito Hagi; Satoshi Abe; Kenji Sato; Yukihiro Yoshida; Yoshiyuki Suehara; Keisuke Akaike; Hiroaki Hiraga; Tamotsu Soma; Hiroshi Kobayashi; Yusuke Shinoda; Ryoko Sawada
    Annals of Surgical Oncology 28 (7) 3919 - 3927 1068-9265 2020 
    © 2020, Society of Surgical Oncology. Background: A prospective cohort study was conducted to determine the incidence and risk factors of symptomatic venous thromboembolism (sVTE) during the perioperative period in patients with malignant bone and soft tissue tumors. Methods: Patients with newly diagnosed primary malignant bone and soft tissue tumors for whom definitive surgery was planned were consecutively registered among 27 tertiary hospitals specializing in musculoskeletal oncology. Clinicopathological information on each patient was collected prospectively, and careful follow-up was conducted for 6 months after surgery. The study endpoint was the occurrence of sVTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Results: Eleven of 929 patients developed sVTE, including 8 patients with DVT, 2 with PE, and 1 with both, making the incidence of sVTE 1.18%. The median time until the development of sVTE after tumor resection was 11 days, ranging from − 7 to 95 days. Multiple logistic regression analyses revealed that ischemic heart disease as a comorbidity, maximum tumor diameter exceeding 8 cm, and elevated preoperative platelet count were independent risk factors for sVTE. Conclusions: The incidence of sVTE in this series of patients with bone and soft tissue sarcomas was 1.18%, which was relatively lower than in previous retrospective studies. We identified the risk factors for sVTE specific to patients with malignant bone and soft tissue tumors, and these included ischemic heart disease, tumor size, and elevation of the preoperative platelet count.
  • Kazuhiko Hashimoto; Shunji Nishimura; Naohiro Oka; Masao Akagi
    SAGE open medicine 8 2050312120923177 - 2050312120923177 2020 [Refereed]
     
    Purpose: This study aimed to evaluate the clinical features and outcomes of osteosarcoma to identify prognostic factors and determine new strategies to improve overall survival. Patients and Methods: We retrospectively analyzed 12 cases of osteosarcoma treated at our hospital from 2012 to 2017. Tumor site, tissue type, stage, treatments, adverse effects, postoperative limb function, surgical margin, and final outcomes were evaluated. Results: All patients received chemotherapy, and 10 underwent wide resection. The Musculoskeletal Tumor Society scores were more than good in all cases, and the 3-year survival rate was 73.3%. Two patients are alive with disease, eight have remained disease-free, and two died of the disease. Three of the four recurrent cases involved the pelvis. Conclusion: The treatment of primary osteosarcoma with wide resection in our department, therefore, yielded favorable outcomes. However, improved treatment strategies are needed for pelvic and advanced cases.
  • Naohiro Oka; Shunji Nishimura; Hiroki Tanaka; Kazuhiko Hashimoto; Ryosuke Kakinoki; Masao Akagi
    Journal of Medical Case Reports Springer Science and Business Media LLC 13 (1) 87  2019/12 [Refereed]
  • Hashimoto K; Nishimura S; Iemura S; Akagi M
    Acta medica Okayama 72 (6) 601 - 604 0386-300X 2018/12 [Refereed]
     
    Salmonella osteomyelitis is extremely rare; only a few cases have been reported in healthy adults. We describe a case of salmonella osteomyelitis in an otherwise healthy 20-year-old Japanese woman who presented with distal tibial pain. X-ray and magnetic resonance imaging showed a lesion suspected to be a bone cyst. Osteomyelitis was diagnosed when pus was observed during an open biopsy. The bacterial culture examination yielded salmonella. Surgical drainage and antibiotic treatment were performed, after which no recurrence was observed. To our best knowledge, this is the first report of salmonella osteomyelitis of the distal tibia in an otherwise healthy individual.
  • Kazuhiko Hashimoto; Shunji Nishimura; Yukiko Hara; Naohiro Oka; Hiroki Tanaka; Shunki Iemura; Masao Akagi
    Experimental and Therapeutic Medicine Spandidos Publications 17 (1) 888 - 894 1792-0981 2018/11 [Refereed]
  • Ryosuke Kakinoki; Kazuhiro Ohtani; Kazuhiko Hashimoto; Hiroki Tanaka; Ryosuke Ikeguchi; Souichi Ohta; Masao Akagi
    Techniques in hand & upper extremity surgery 22 (3) 110 - 115 1089-3393 2018/09 [Refereed]
     
    Dupuytren's pathologic tissue usually involves the palmar skin and rarely infiltrates into the dorsal skin. In this study, we hypothesized that transplantation of a vascularized cutaneous flap harvested from the dorsum of the hand to the palmar skin, under which the pathologic cord existed might be useful for blocking reformation of the pathologic cords and for decreasing the recurrence rate. After removal of the pathologic tissue under the palmar skin, we harvested 2 types of skin islands nourished by the dorsal digital arterial network including the dorsal perforating arteries arising from the palmar digital arteries. The skin islands were transplanted into skin defects in the palm of the fingers and hand that had been created after correction of flexion contracture of the fingers. We performed this surgical maneuver on 24 fingers in 24 patients who exhibited severe flexion contracture because of Dupuytren disease. During the mean 40-month follow-up, only 1 patient experienced metacarpophalangeal joint flexion contracture ≥20 degrees in the operated finger. The recurrence rate was 4.2%, which was almost similar to that for a dermofasciectomy followed by a large full-thickness skin graft.
  • Hashimoto K; Nishimura S; Kakinoki R; Akagi M
    BMC Res Notes in press (1) 628  2018/08 [Refereed]
  • Kotaro Yamagishi; Ichiro Tsukamoto; Fumihisa Nakamura; Kazuhiko Hashimoto; Kazuhiro Ohtani; Masao Akagi
    European Journal of Histochemistry PAGEPress Publications 62 (3) 1121-760X 2018/07 [Refereed]
     
    Epidemiological studies have shown an association between hypertension and knee osteoarthritis (OA). The purpose of this study was to investigate whether activation of the renin–angiotensin system (RAS) can aggravate mechanical loading-induced knee OA in mice. Eight-week-old male Tsukuba hypertensive mice (THM) and C57BL/6 mice were divided into running and non-running groups. Mice in the running group were forced to run (25 m/min, 30 min/day, 5 days/week) on a treadmill. All mice in the four groups (n=10 in each group) were euthanized after 0, 2, 4, 6, or 8 weeks of running or natural breeding. Cartilage degeneration in the left knees was histologically evaluated using the modified Mankin score. Expression of Col X, MMP-13, angiotensin type 1 receptor (AT1R), and AT2R was examined immunohistochemically. To study the effects of stimulation of the AT1R in chondrocytes by mechanical loading and/or Angiotensin II (AngII) on transduction of intracellular signals, phosphorylation levels of JNK and Src were measured in bovine articular chondrocytes cultured in three-dimensional agarose scaffolds. After 4 weeks, the mean Mankin score for the lateral femoral condylar cartilage was significantly higher in the THM running group than in the C57BL/6 running group and non-running groups. AT1R and AT2R expression was not detected at 0 weeks in any group but was noted after 4 weeks in the THM running group. AT1R expression was also noted at 8 weeks in the C57BL/6 running group. The expression levels of AT1R, COL X, and MMP-13 in chondrocytes were significantly higher in the THM running group than in the control groups. Positive significant correlations were noted between the Mankin score and the rate of AT1R-immunopositive cells, between the rates of AT1R- and Col X-positive cells, and between the rates of AT1R- and AT2R-positive cells. The phosphorylation level of JNK was increased by cyclic compression loading or addition of AngII to the cultured chondrocytes and was reversed by pretreatment with an AT1R blocker. A synergistic effect on JNK phosphorylation was observed between compression loading and AngII addition. Transgene activation of renin and angiotensinogen aggravated mechanical load-induced knee OA in mice. These findings suggest that AT1R expression in chondrocytes is associated with early knee OA and plays a role in the progression of cartilage degeneration. The RAS may be a common molecular mechanism involved in the pathogenesis of hypertension and knee OA.
  • Kazuhiko Hashimoto; Masao Akagi
    Molecular and Clinical Oncology Spandidos Publications 9 (3) 293 - 296 2049-9450 2018/07 [Refereed]
  • Kazuhiko Hashimoto; Shunji Nishimura; Masao Akagi
    Cureus Cureus, Inc. in press (7) e2954  2168-8184 2018/07 [Refereed]
  • Kazuhiko Hashimoto; Shunji Nishimura; Naohiro Oka; Hiroki Tanaka; Ryosuke Kakinoki; Masao Akagi
    Molecular and Clinical Oncology Spandidos Publications 9 (3) 310 - 314 2049-9450 2018/07 [Refereed]
  • Kazuhiko Hashimoto; Shunji Nishimura; Naohiro Oka; Ryosuke Kakinoki; Masao Akagi
    Molecular and Clinical Oncology Spandidos Publications 9 (2) 207 - 210 2049-9450 2018/06 [Refereed]
  • LOX-1-deficient mice are resistant to zymosan-induced arthritis: A mini review
    Hashimoto K; Oda Y; Yamagishi K; Tsukamoto I; Akagi M
    Journal of Immunological Sciences 2 (3) 2018/06 [Refereed][Invited]
  • Kazuhiko Hashimoto; Shunji Nishimura; Ryosuke Kakinoki; Masao Akagi
    Molecular and Clinical Oncology Spandidos Publications 9 (1) 62 - 65 2049-9450 2018/05 [Refereed]
  • Hashimoto K; Oda Y; Mori S; Yamagishi K; Tsukamoto I; Akagi M
    J Rare Dis Res 3 (2) 22 - 24 2018/05 [Refereed]
  • 西村俊司; 岡尚宏; 橋本和彦; 朝田滋貴; 柿木良介; 赤木將男
    日本骨・感染症学会雑誌 (一社)日本骨・関節感染症学会 31 82 - 84 1881-9893 2018/03 [Refereed]
     
    68歳男性。発熱、腰痛を主訴に前医を受診、悪性リンパ腫または腸腰筋膿瘍を疑われ、当院へ紹介となった。CTでは左腸骨筋膿瘍に加え、脾臓のないことが確認され、CTガイド下ドレナージを行い、膿瘍の流出を認めた。入院加療となり、CEZの抗菌薬治療と共に、局所の培養と血液培養よりS.pneumoniaeが検出された。入院4日目には出血性ショックを呈し、消化管穿孔と診断され、胃全摘術を行うことで、一命を取り留めた。その後、ICU管理で抗菌薬を継続したが、腸骨筋膿瘍は改善せず、化膿性股関節炎も合併していたため、腸骨筋膿瘍の洗浄術および股関節内洗浄、デブリ、滑膜切除、骨頭除去を行い、VCM20%含有セメントモールドを挿入した。いずれも培養結果は肺炎球菌であり、術後は抗菌薬を1ヵ月間にわたり経静脈的に投与後、内服へ変更し、感染の鎮静化が得られた。初診より3ヵ月で退院となり、術後2年経過現在、1本杖歩行が可能で、感染の再燃はみられていない。
  • Kazuhiko Hashimoto; Yutaka Oda; Koichi Nakagawa; Terumasa Ikeda; Kazuhiro Ohtani; Masao Akagi
    European Journal of Histochemistry PAGEPress Publications 62 (1) 2847 - 41 1121-760X 2018/01 [Refereed]
     
    Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.
  • Kazuhiko Hashimoto; Shunji Nishimura; Kousuke Fujii; Ryosuke Kakinoki; Masao Akagi
    Rare Tumors SAGE Publications 10 203636131877649 - 203636131877649 2036-3613 2018/01 [Refereed]
  • Kazuhiko Hashimoto; Ryosuke Kakinoki; Yukiko Hara; Naohiro Oka; Hiroki Tanaka; Kazuhiro Ohtani; Masao Akagi
    Open Journal of Rheumatology and Autoimmune Diseases Scientific Research Publishing, Inc. 08 (02) 66 - 70 2163-9914 2018 [Refereed]
  • Kazuhiko Hashimoto; Kensuke Toriumi; Yukiko Hara; Shunki Iemura; Shunji Nishimura; Masao Akagi
    Open Journal of Orthopedics Scientific Research Publishing, Inc. 08 (04) 168 - 174 2164-3008 2018 [Refereed]
  • Kazuhiko Hashimoto; Shunji Nishimura; Kensuke Toriumi; Shunki Iemura; Naohiro Oka; Masao Akagi
    Open Journal of Orthopedics Scientific Research Publishing, Inc. 08 (05) 175 - 182 2164-3008 2018 [Refereed]
  • Hashimoto K; Nishimura S; Fujii K; Kakinoki R; Akagi M
    Rare tumors 10 2036361318776495  2036-3605 2018 [Refereed]
  • Shunji Nishimura; Kazuhiko Hashimoto; Akihiro Tan; Yukinobu Yagyu; Masao Akagi
    Molecular and Clinical Oncology Spandidos Publications 6 (3) 307 - 310 2049-9450 2017/03 [Refereed]
  • Kazuhiko Hashimoto; Yutaka Oda; Fumihisa Nakamura; Ryosuke Kakinoki; Masao Akagi
    EUROPEAN JOURNAL OF HISTOCHEMISTRY PAGEPRESS PUBL 61 (1) 49 - 56 1121-760X 2017 [Refereed][Invited]
     
    The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00 +/- 0.61) and LOX-1 KO mice (2.00 +/- 0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75 +/- 0.93 and 5.50 +/- 0.78) were significantly lower than those of WT mice (5.25 +/- 1.14 and 9.00 +/- 1.01; P<0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression.
  • Kakinoki R; Hashimoto K; Tanaka H; Akagi M
    Journal of orthopaedic case reports 6 (6) 50 - 53 2250-0685 2017/01 [Refereed]
  • Kazuhiko Hashimoto; Yutaka Oda; Fumihisa Nakamura; Ryosuke Kakinoki; Masao Akagi
    EUROPEAN JOURNAL OF HISTOCHEMISTRY PAGEPRESS PUBL 61 (1) 49 - 56 1121-760X 2017 [Refereed]
     
    The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00 +/- 0.61) and LOX-1 KO mice (2.00 +/- 0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75 +/- 0.93 and 5.50 +/- 0.78) were significantly lower than those of WT mice (5.25 +/- 1.14 and 9.00 +/- 1.01; P<0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression.
  • K. Hashimoto; S. Mori; Y. Oda; A. Nakano; T. Sawamura; M. Akagi
    SCANDINAVIAN JOURNAL OF RHEUMATOLOGY TAYLOR & FRANCIS LTD 45 (5) 412 - 422 0300-9742 2016/09 [Refereed]
     
    Objectives: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA. Method: OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and Lox-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression. Results: In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX-1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression. Conclusions: These data indicate that the LOX-1/ox-LDL system plays a pivotal role in the pathogenesis of instability induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte-forming cells may be possible targets to prevent disease progression in OA.
  • 西村俊司; 橋本和彦; 赤木將男
    中部整形外科学会雑誌 57 (3) 639 - 640 2014/05 [Refereed]
  • K. Hashimoto; Y. Oda; I. Tsukamoto; M. Okumoto; A. Nakano; T. Sawamura; M. Akagi
    OSTEOARTHRITIS AND CARTILAGE ELSEVIER SCI LTD 22 (Suppl.S) S362 - S362 1063-4584 2014/04 [Refereed]
     
    Purpose: LOX-1, a vascular endothelial cell receptor for oxidized low-density lipoprotein (ox-LDL), is reportedly involved in the progression of knee osteoarthritis (OA); however, the underlying mechanism has not been elucidated. In the present study, we established a mouse model of OA through destabilization of the medial meniscus (DMM) to investigate the role of LOX-1 in the pathogenesis of OA progression.

    Methods: In this study, we used 9-week-old LOX-1+/+ and LOX-1-/- mice. The mice underwent DMM at the right knee (DMM side) as well as a skin incision along with placement of a joint capsule on the contralateral knee (sham-operation side). Samples were obtained from both the knee joints at 4 and 8 weeks after surgery. Safranin staining was performed for each section to assess the osteoarthritic change. Cartilage degeneration, osteophyte formation were assessed by using a scoring system . Moreover, the expression levels of LOX-1 and ox-LDL were assessed in each sample by immunostaining.

    Results: On the DMM side, osteophyte formation and cartilage degeneration were significantly suppressed in LOX-1-/- mice at 8 weeks after surgery. However, no significant difference in osteophyte formation or cartilage degeneration was noted on the sham-operation side at both 4 and 8 weeks; OA progression was only slightly observed among these mice . Expression was observed cartilage cells, the formation of osteophytes section . Moreover, the expression levels of LOX-1 and ox-LDL in LOX-1+/+ mice were found to be increased from 4 weeks to 8 weeks after surgery.

    Conclusions: Thus, we believe that LOX-1 may play an important role in the pathogenesis of OA progression. Moreover, we suggest that LOX-1 could be used as a potential target for the prevention and treatment of OA progression.
  • 結核性膝関節炎の2例
    橋本和彦; 森成志; 朝田滋貴; 赤木將男
    日本骨感染症学会雑誌 27 115 - 118 2014/03 [Refereed]
  • HASHIMOTO Kazuhiko
    The Central Japan Journal of Orthopaedic Surgery & Traumatology THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 57 (5) 993 - 994 0008-9443 2014 [Refereed]
  • Shigeshi Mori; Masao Akagi; Shigeki Asada; Tetsunao Matsushita; Kazuhiko Hashimoto
    CLINICAL ORTHOPAEDICS AND RELATED RESEARCH SPRINGER 471 (5) 1465 - 1471 0009-921X 2013/05 [Refereed]
     
    Tibia vara seen in Japanese patients reportedly influences the tibial component alignment when performing TKA. However, it is unclear whether tibia vara affects the component position and size selection. We therefore determined (1) the amount of medial tibial bow, (2) whether the tibia vara influences the aspect ratio of the tibial resected surface in aligning the tibial component with the tibial shaft axis, and (3) whether currently available tibial components fit the shapes of resected proximal tibias in terms of aspect ratio. We measured the tibia vara angle (TVA), proximal varus angle (PVA), and the mediolateral and middle AP dimensions of the resected surface using three-dimensional preoperative planning software in 90 knees of 74 female patients with varus osteoarthritis. We determined the correlations of the aspect ratio with TVA or PVA and compared the aspect ratios to those of five prosthesis designs. The mean TVA and PVA were 0.6A degrees and 2.0A degrees, respectively. The aspect ratio negatively correlated with both TVA and PVA (r = -0.53 and -0.55, respectively). The mean aspect ratio of the resected surface was 1.48 but gradually decreased with increasing AP dimension, whereas four of the five prostheses had a constant aspect ratio. The aspect ratio of resected tibial surface was inversely correlated to the degree of tibia vara, and currently available prosthesis designs do not fit well to the resected surface in terms of aspect ratio. The design of a tibial component with a smaller aspect ratio could be developed to obtain better bone coverage in Japanese patients.
  • HASHIMOTO Kazuhiko
    The Central Japan Journal of Orthopaedic Surgery & Traumatology THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 56 (1) 203 - 204 0008-9443 2013/01 [Refereed]
  • HASHIMOTO Kazuhiko
    The Central Japan Journal of Orthopaedic Surgery & Traumatology THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 56 (4) 835 - 836 0008-9443 2013/01 [Refereed]
  • I. Tsukamoto; M. Akagi; S. Inoue; T. Teramura; T. Takehara; Y. Onodera; K. Hashimoto; C. Hamanishi
    OSTEOARTHRITIS AND CARTILAGE ELSEVIER SCI LTD 20 (Suppl. 1) S151 - S151 1063-4584 2012/04 [Refereed]
     
    Purpose: Recently, the local renin-angiotensin system (RAS) has attracted many researchers in many pathophysiological issues. In Orthopedics, expression of local RAS was found in bone tissues, fracture callus and arthritic synovium. The purpose of this study is to reveal immunohistological localization of the RAS components in the epiphyseal plates of mice and to analyze function of the local RAS in the processes of hypertrophic differentiation using ATDC5 chondroprogenitor cells.

    Methods: The epiphyseal plates of 8-week-old mice was immunostained with antibodies to angiotensinogen, angiotensinogen converting enzyme 1 (ACE1), angiotensinII type 1 receptor (AT1R) and angiotensinII type 2 receptor (AT2R). We cultured ATDC5 in long term and evaluated the expression of angiotensinogen, ACE1, AT1R, AT2R and type 2 collagen (COL2) by real- time PCR and Western blot analysis.

    Results: In the epiphyseal plates of mice, angiotensinogen and AT1R expressed in the resting chondrocytes, the proliferative chondrocytes and hypertrophic chondrocytes; however, ACE1 and AT2R expressed only in the hypertrophic chondrocytes. In ATDC5 chondroprogenitor cells, the local RAS components expressed both in proliferative and hypertrophic differentiating stages.

    Conclusions: The local RAS expresses in the epiphyseal plates of mice and might play an important role in the process of hypertrophic differentiation.
  • 橋本 和彦; 赤木 将男
    近畿大医誌 近畿大学医学会 37 (1.2) 11 - 19 0385-8367 2012/03 [Refereed]
     
    [抄録] 目的:非侵襲性で再現性に優れたマウス変形性膝関節症(OA)モデルを作製し, その特性を明らかにする. 方法:マウス用走行強制トレッドミルを使用した.(1)経時的変化観察群:マウスに1回15分, 11m/分の速度, 1週間に3回(2週間当たりの走行距離1km)で, 2, 4, 6, 8週間の走行負荷を加えた(各n=4).(2)走行時間変化群:短時間走行群(1回7.5分, 1週間に3回走行)と長時間走行群(1回30分, 1週間に3回走行)を2週間走行させた(各n=4).膝関節の変形はX線的および組織学的に評価した.関節軟骨変性の評価には国際関節症学会(OARSI)評価スケールを用いた.また軟骨変性のマーカーであるII型コラーゲンおよびX型コラーゲンの発現変化を免疫染色にて評価した. 結果:組織学的変化:半月板骨化, 骨棘形成, 十字靱帯変性および断裂, 関節軟骨変性が認められ, これらの変化の出現頻度は経時的に増加した.OARSIスコア:経時的変化観察群および走行時間変化群の両群において, それぞれ走行週数および一回当たり走行時間に依存してスコアは増加した.また, OA変化は全て膝内側コンパートメントに比較し外側コンパートメントに顕著であった.関節軟骨におけるII型コラーゲンの発現は走行負荷により減少し, X型コラーゲンは発現の増加がみられた. 結論:本モデルの利点として運動負荷が生理的であること, 作成方法の単純さと非侵襲性, そして何よりもOAの高い再現性および調節性が挙げられる.そして, 遺伝子操作が可能なマウスを使用する本モデルでは, 機械的負荷によるOAの発症および進行を, 遺伝子レベルにおいて解明できる可能性が大きく示された.
  • HASHIMOTO Kazuhiko
    The Central Japan Journal of Orthopaedic Surgery & Traumatology THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 53 (5) 1037 - 1038 2010/09 [Refereed]
  • Tan A; Hashimoto K; Matsuzaki M; Akagi M; Fukuda K; Hamanishi C
    Acta Medica Kinki University The Kinki University Medical Association 35 (1) 53 - 56 0386-6092 2010/06 [Refereed]
     
    Chondrolipoma is a rare benign mesenchymoma composed of mature cartilage and adipose tissue. Here we present a 33-year-old woman with chondrolipoma of the ankle. She had been aware of a growing, solid mass on the front part of the right ankle for six months. On examination, a elastic hard mass of 3×3cm, with no adhesion to the skin, but to the base was observed. She underwent the marginal resection of the tumor. No local recurrence has been noted for 5 months postoperatively.
  • 橋本和彦; 冨山貴司; 大谷和裕; 浜西千秋
    Orthopaedic surgery and traumatology 金原出版 53 (6) 767 - 770 0387-4095 2010/05 [Refereed]
  • 肘部管症候群に対する前方移動術
    大谷和裕; 冨山貴司; 橋本和彦; 福田寛二; 浜西千秋
    20 (2) 223 - 224 2009 [Refereed]

MISC

Books and other publications

  • 動物/疾患モデルの作製技術・病態解析・評価手法
    橋本和彦 (Joint work第2節 動物変形性関節症(OA)モデルの作製法)(株) 技術情報協会 2017/08
  • 整形外科
    橋本和彦 (ContributorVocaburaly(LOX-1))南江堂 2015/03

Lectures, oral presentations, etc.

  • 生活習慣病と変形性関節症  [Invited]
    橋本和彦
    第48回関節病学会  2020/10
  • 神経鞘腫による神経障害性疼痛に対するプレガバリンの効果  [Not invited]
    西村俊司; 橋本和彦; 赤木將男
    第50回 日本整形外科学会骨軟部腫瘍学術集会  2017/07
  • 爪下に発生したsuperficial acral fibromyxomaの1例  [Not invited]
    橋本和彦; 西村俊司; 赤木將男
    第50回 日本整形外科学会骨軟部腫瘍学術集会  2017/07
  • 骨線維性異形成症の経過中に合併した脛骨骨肉腫の1例  [Not invited]
    西村俊司; 橋本和彦; 朝田滋貴; 岡尚宏; 柿木良介; 赤木將男
    第50回 日本整形外科学会骨軟部腫瘍学術集会  2017/07
  • 治療に難渋した骨髄炎に対する抗生剤入りセメント挿入時の二期的血管柄付き組織移植  [Not invited]
    中村文久; 柿木良介; 橋本和彦; 田中寛樹; 赤木將男
    第40回 日本骨感染症学会  2017/06
  • デュピュイトラン拘縮に対するコラゲナーゼ注射法と外科的手術療法の比較検討  [Not invited]
    橋本和彦; 柿木良介; 田中寛樹; 赤木將男
    第60回日本手の外科学会  2017/04
  • 治療に難渋した母指示指発生の好酸球血管リンパ増殖症の1例  [Not invited]
    岡尚宏; 西村俊司; 橋本和彦; 柿木良介; 赤木將男
    第128回 中部整形外科災害外科学会  2017/04
  • 肋軟骨移植および血管柄付き骨移植術を必要とした舟状骨偽関節の1例  [Not invited]
    橋本和彦; 柿木良介; 岡尚宏; 田中寛樹; 赤木將男
    第128回 中部整形外科災害外科学会  2017/04
  • 腕神経叢損傷患者に対する部分神経移行術による上肢機能再建  [Not invited]
    柿木良介; 橋本和彦; 田中寛樹; 池口良輔; 太田壮一; 赤木將男
    第43回 マイクロサージャリー学会学術集会  2016/11
  • 腸骨部に発生した類血管型線維性組織球腫の1例  [Not invited]
    橋本和彦; 西村俊司; 赤木將男
    第49回 日本整形外科学会骨軟部腫瘍学術集会  2016/07
  • 高齢者に発生した悪性骨軟部腫瘍の治療経験  [Not invited]
    橋本和彦; 西村俊司; 赤木將男
    第126回中部日本整形外科災害外科学会  2016/04
  • 30年以上経過後に悪性転化した大腿骨巨細胞腫の1例  [Not invited]
    西村俊司; 橋本和彦; 朝田滋貴; 柿木良介; 赤木將男
    第48回日本整形外科学会骨軟部腫瘍学術集会  2015/07
  • デスモイド腫瘍における疼痛におけるLOX-1/酸化LDL系の関与  [Not invited]
    橋本和彦; 西村俊司; 奥本勝美; 赤木將男
    第48回日本整形外科学会骨軟部腫瘍学術集会  2015/07
  • 悪性軟部腫瘍との鑑別を要した結核腫の2例  [Not invited]
    橋本和彦; 西村俊司; 奥本勝美; 赤木將男
    第48回日本整形外科学会骨軟部腫瘍学術集会  2015/07
  • 血行再建を必要とした脛骨神経発生滑膜肉腫の1例  [Not invited]
    橋本和彦; 西村俊司; 赤木將男
    第29回 近整会学術集会  2015/01
  • レニン・アンギオテンシン系の亢進によるOA変化の検討  [Not invited]
    山岸孝太郎; 墳本一郎; 井上紳司; 橋本和彦; 赤木將男
    第29回 日本整形外科学会基礎学術集会  2014/10
  • Adefovir dipivoxilによる薬剤性骨軟化症の1例  [Not invited]
    西地晴彦; 橋本和彦; 西村俊司; 池田光正; 赤木將男
    第123回 中部日本整形外科災害外科学会  2014/10
  • COX-2はデスモイド腫瘍の増大に関与する  [Not invited]
    橋本和彦; 西村俊司; 赤木將男
    第47回日本整形外科学会骨軟部腫瘍学術集会  2014/07
  • 軟部肉腫における胎児型ヘモグロビンの発現の検討  [Not invited]
    西村俊司; 橋本和彦; 赤木將男
    第47回 日本整形外科学会・骨軟部腫瘍学術集会  2014/07
  • 悪性骨軟部腫瘍との鑑別を要した脛骨限局性赤色髄化の1例  [Not invited]
    橋本和彦; 西村俊司; 中村文久; 赤木將男
    第122回 中部日本整形外科災害外科学会  2014/04
  • 高血圧によるOA変化:つくば高血圧モデルマウスを用いた検討  [Not invited]
    山岸孝太郎; 墳本一郎; 橋本和彦; 井上紳司; 橋本和彦; 赤木將男
    第27回 日本軟骨代謝学会  2014/02
  • 保存治療により寛解した結核性膝関節炎の1例  [Not invited]
    橋本和彦; 森成志; 朝田滋貴; 赤木將男
    第41回 日本関節病学会  2013/11
  • LOX-1の欠損によりマウスの変形性膝関節症の進行が抑制される  [Not invited]
    橋本和彦; 赤木將男; 小田豊; 奥本勝美; 中野厚史; 沢村達也
    第28回 日本整形外科基礎学術集会  2013/10
  • 超高齢者の軟部肉腫の治療経験(パネルディスカッション1)  [Not invited]
    橋本和彦; 西村俊司; 丹彰浩; 赤木將男
    第121回 中部整形外科災害外科学術集会  2013/10
  • MTX使用中に非ホジキン悪性リンパ腫を発症したRA患者の1例  [Not invited]
    橋本和彦; 赤木將男
    第23回 南大阪リウマチ研究会  2013/09
  • 異なる遺伝子型の野生型マウスでの強制走行負荷による変形性膝関節症様変化の検討  [Not invited]
    橋本和彦; 小田豊; 墳本一郎; 赤木將男; 奥本勝美
    第72回 近畿大学医学会学術講演会  2013/07
  • Tibia Vara Affects the Aspect Ration of Tibial Resected Surface in Female Japanese Patients Undergoing TKA  [Not invited]
    森 成志; 朝田 滋貴; 井上 紳司; 中川 晃一; 橋本 和彦; 赤木 将男; 松下 哲尚
    The 23rd Korean-Japanese Combined Orthopaedic Symposium  2013/06  Buyeo Korea  The 23rd Korean-Japanese Combined Orthopaedic Symposium
  • 単顆型人工膝関節の前額面アライメントに対する脛骨近位内方傾斜の影響  [Not invited]
    森 成志; 朝田 滋貴; 西地 晴彦; 中川 晃一; 橋本 和彦; 赤木 将男; 井上 紳司
    第5回日本関節鏡・膝・スポーツ整形外科学会  2013/06  札幌  第5回日本関節鏡・膝・スポーツ整形外科学会
  • Stress analysis of the medial tibial condyle in the unicompartmental knee arthroplasty:Effects of the tibial implant alignment  [Not invited]
    井上 紳司; 赤木 将男; 朝田 滋貴; 森 成志; 西坂 文章; 橋本 和彦; 中川 晃一
    The 23rd Korean-Japanese Combined Orthopaedic Symposium  2013/06  Buyeo Korea  The 23rd Korean-Japanese Combined Orthopaedic Symposium
  • Zymosan誘発性関節炎モデルマウスにおけるLOX-1の滑膜炎と軟骨変性に対する関与の検討  [Not invited]
    小田豊; 橋本和彦; 墳本一郎; 赤木將男
    第26回 軟骨代謝学会  2013/03
  • 機能軸を参照可能な新脛骨髄外ガイドの骨切り精度検証  [Not invited]
    朝田 滋貴; 森 成志; 中川 晃一; 橋本 和彦; 井上 紳司; 赤木 将男; 松下 哲尚
    第43回日本人工関節学会  2013/02  京都  第43回日本人工関節学会
  • 大腿骨コンポーネント挿入に伴う関節Gap長の縮小が人工膝関節置換術直後の膝伸展角度に与える影響  [Not invited]
    森 成志; 朝田 滋貴; 西坂 文章; 井上 紳司; 中川 晃一; 橋本 和彦; 西地 晴彦; 赤木 将男; 松下 哲尚
    第43回日本人工関節学会  2013/02  京都  第43回日本人工関節学会
  • C‐stem AMTの使用経験  [Not invited]
    西坂 文章; 福田 寛二; 中川 晃一; 井上 紳司; 橋本 和彦; 赤木 将男
    第39回日本股関節学会学術集会  2012/12  新潟  第39回日本股関節学会学術集会
  • 人工膝関節置換術における術後抗凝固薬使用の意義-静脈エコーによる経時的観察の結果より-(シンポジウム7:関節疾患手術における抗凝固剤の是非)  [Not invited]
    森 成志; 朝田 滋貴; 中川 晃一; 橋本 和彦; 橋本 和喜; 松下 哲尚; 赤木 将男
    第40回日本関節病学会  2012/11  鹿児島  第40回日本関節病学会
  • 3Dテンプレートによる術前計画(シンポジウム TKAのアライメントはどうあるべきか)  [Not invited]
    朝田 滋貴; 赤木 将男; 森 成志; 松下 哲尚; 中川 晃一; 橋本 和彦
    第40回日本関節病学会  2012/11  鹿児島  第40回日本関節病学会
  • 強制走行負荷による非侵襲性マウス変形性膝関節症モデルの作成  [Not invited]
    橋本 和彦; 赤木 将男
    第3回ヒアルロン酸研究会  2012/10  名古屋  第3回ヒアルロン酸研究会
  • 薬物予防下での人工膝関節術後無症候性深部静脈血栓の術後経過-術後抗凝固薬使用意義についての検討-  [Not invited]
    森 成志; 朝田 滋貴; 橋本 和彦; 橋本 和喜; 松下 哲尚; 赤木 将男
    第119回中部日本整形外科災害外科学会  2012/10  福井  第119回中部日本整形外科災害外科学会
  • 反復性膝蓋骨脱臼に対するMPFL縫縮術の短期成績  [Not invited]
    朝田 滋貴; 森 成志; 橋本 和彦; 松下 哲尚; 中川 晃一; 赤木 将男
    第119回中部日本整形外科災害外科学会  2012/10  福井  第119回中部日本整形外科災害外科学会
  • 自家骨軟骨柱移植術後成績改善率に影響する因子の検討  [Not invited]
    橋本 和彦; 朝田 滋貴; 森 成志; 赤木 将男
    第119回中部日本整形外科災害外科学会  2012/10  福井  第119回中部日本整形外科災害外科学会
  • 成長軟骨帯およびATDC5におけるlocal RASの検討  [Not invited]
    墳本一郎; 赤木將男; 井上紳司; 寺村岳士; 竹原俊幸; 小野寺勇太; 橋本和彦; 浜西千秋
    第25回 日本軟骨代謝学会  2012/03
  • 強制走行負荷によるマウス変形性膝関節症モデルの検討  [Not invited]
    橋本 和彦; 赤木 将男; 岸本 英樹; 濵西 千秋; 寺村 岳士; 小野寺 勇太
    第25回日本軟骨代謝学会  2012/03  名古屋  第25回日本軟骨代謝学会
  • 強制走行負荷による非侵襲性マウス変形性膝関節症モデルの検討  [Not invited]
    橋本和彦; 赤木將男; 岸本英樹; 浜西千秋; 寺村岳士; 小野寺勇太
    第25回 日本軟骨代謝学会  2012/02
  • 成長軟骨帯内軟骨骨化におけるRASの関与  [Not invited]
    井上 紳司; 赤木 将男; 橋本 和彦; 墳本 一郎; 濵西 千秋; 寺村 岳士; 竹原 俊幸; 小野寺 勇太
    第39回日本関節病学会  2011/11  横浜  第39回日本関節病学会
  • 走行負荷でのマウス膝関節変形の検討  [Not invited]
    橋本 和彦; 赤木 将男; 岸本 英樹; 濵西 千秋; 寺村 岳士; 小野寺 勇太
    第39回日本関節病学会  2011/11  横浜  第39回日本関節病学会
  • 非侵襲性OAモデルマウスと侵襲性OAモデルマウスの比較検討  [Not invited]
    橋本 和彦; 赤木 将男; 岸本 英樹; 濵西 千秋; 寺村 岳士; 小野寺 勇太
    第26回日本整形外科学会基礎学術集会  2011/10  前橋  第26回日本整形外科学会基礎学術集会
  • Osteoarthritis-like changes in the murine knee joint by means of forced running  [Not invited]
    橋本 和彦; 赤木 将男
    2011 World Congress on Osteoarthritis  2011/09  San Diego  2011 World Congress on Osteoarthritis
  • 走行負荷でのマウス膝関節変形の検討  [Not invited]
    橋本 和彦; 赤木 将男; 岸本 英樹; 濵西 千秋; 寺村 岳士; 小野寺 勇太
    第70回近畿大学医学会  2011/07  第70回近畿大学医学会
  • 走行負荷でのマウス膝関節変形の検討  [Not invited]
    橋本 和彦; 赤木 将男; 岸本 英樹; 濵西 千秋; 寺村 岳士; 小野寺 勇太
    第24回日本軟骨代謝学会  2011/03  福岡  第24回日本軟骨代謝学会

Affiliated academic society

  • 日本臨床腫瘍学会   日本関節病学会   日本手の外科学会   日本がん治療学会   THE JAPANESE ORTHOPAEDIC ASSOCIATION   

Research Themes

  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 赤木 將男; 橋本 和彦; 墳本 一郎
     
    1)DMM (内側半月板不安定化) 手術:動物実験は全て医学部共同研究施設実験動物共同研究室の倫理委員会の承認を経て行った。実験には40週齢のC57BL/6雄マウスを使用し、左膝にDMM (内側半月板不安定化) 手術を全身麻酔下に施行した。まず、膝蓋骨近位から脛骨平原遠位まで約1cmの正中皮膚切開を行った。次に、内側傍膝蓋アプローチにて関節包を切開し、関節内内側から顆間領域を露出させた。Medial meniscus (MM)とMedial menisco-tibial ligament (MMTL)を同定した。その後、MMTLを尖刃刀で切離しMMが不安定化したことを確認した。生理食塩水で洗浄後に、関節包と皮膚を5-0ナイロンで閉創した。右膝にはSham手術(皮膚と関節包のみをDMM側と同様に切開、生理食塩水で洗浄後に同様に閉創)を実施した。手術後はケージ内で自然飼育とした。術後0, 1, 2, 4, 8週(各群n=3)でマウスを安楽死させた。 2)軟骨変性の評価:DMM手術後の経時的な軟骨変性の程度をSafranin-O染色により評価した。評価にはModified Mankin Scoreを用いた。DMM群ではSham群に比較して術後2週から軟骨変性が進行する傾向が認められ、術後4, 8週でModified Mankin Scoreには統計学的に有意な差を認めた。 3)軟骨下骨骨粗鬆化の評価:脛骨骨端線より近位の骨量を新たに購入したマイクロCT(Rigaku社製のCosmo Scan GXⅡ)を使用して行った。撮影条件は148μm等方性ボクセルサイズ、電圧90kV、電流88μA、撮影時間は4分とした。解析パラメーターは軟骨下骨のbone volume density (BV/TV)とし、マイクロCTに付属の自動解析ソフトを使用して評価した。DMM群ではSham群に比較して術後1-2週からBV/TVが減少する傾向が認められ、術後4, 8週で統計学的に有意な差を認めた。 4)各群はn=3と少なくデータの信頼度は低いが、DMM手術により、関節軟骨と軟骨下骨の骨粗鬆化が同時に進行する傾向があることが分かった
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : AKAGI Masao; ASADA Shigeki; HASHIMOTO Kazuhiko; SAWAMURA Tatsuya; TERAMURA Takeshi
     
    Purpose of this study is to demonstrate involvement of the ox-LDL/LOX-1 system to joint cartilage degeneration in vivo using LOX-1 knockout (KO) mouse. To develop a nonsurgical murine knee osteoarthritis model, mechanical load is applied by forced running on a treadmill, which was controlled by changing number of forced running periods and running time. Changes in the degeneration score increased significantly in a time- and dose-dependent manner. However, LOX-1 KO did not show significant protective effects in this OA model after 2-week forced running, compared with wild type mice. While, long-term observation (1 and 1.5 year) of the KO mice and wild type mice bred conventionally in cages revealed significant difference in cartilage degeneration. Furthermore, LOX-1 KO suppressed synovitis and cartilage degeneration in zymosan induced arthritis. These results indicate that the ox-LDL/LOX-1 system is involved to joint cartilage degeneration in vivo. In conclusion, the ox-LDL/LOX-1 system may play some role not only in endothelial dysfunction of atherosclerosis but also in cartilage degeneration.