RESEARCH研究

2020 研究業績・論文発表

論文

Kakinoki R, Ikeguchi R, Ohta S, Nishichi H, Tanaka H, Otani K, Akagi M.

Comparison between capsular and transossous suture techniques for treatment of triangular fibrous cartilage complex injuries with distal radio-ulnar joint instability.

Acta Scientific Orthopaedics 4(1)31-37 2020年12月

Iemura S, Kawao N, Akagi M, Kaji H.

Role of Dkk2 in the muscle/bone interaction of androgen-deficient mice.

Exp Clin Endocrinol Diabetes. 2020.12.22online掲載

Nakamura T, Sugaya J, Kobayashi H, Okuma T, Kunisada T, Asanuma K, Nishimura S, et al.

Standard treatment remains the recommnended approach for patients with bone sarcoma who underwent unplanned surgery : report from the Japanese Musculoskeletal Oncology Group.

Cancer Manag Res 12 10017-10022 2020年10月

Yamada K, Ito Y M, Akagi M, Chosa E, Hirano K, et al.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years : a cross-sectional nationwide study in Japan.

J Orthop Sci 25(6)1084-1092 2020年11月

Iwata S, Kawai A, Ueda T, …Nishimura S, Hashimoto K, et al. Japanese Musculoskeletal Oncology Group (JMOG).

Symptomatic venous thromboembolism in patients with malignant bone and soft tissue tumors: a prospective multicenter cohort study.

Ann Surg Oncol 2020年11月

Tsukamoto I, Akagi M, Mori S, Inoue S, Nakagawa K, Yamagishi K.

Referencing the substitute anteroposterior line of the tibia improves rotational alignment of the tibial component in medial unicompartmental knee arthroplasty

The Knee 27(5) 1458 - 1466 2020年10月

Hashimoto K, Nishimura S, Matsumura D, Otani K, Akagi M.

Salmonella Osteomyelitis of the Rib Mimicking a Mammary Tumor: A Case Report.

The Tohoku journal of experimental medicine 251(4) 273 - 277 2020年8月
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.

Oka N, Komuro A, Amano H, Dash S, Honda M, Ota K, Nishimura S, Ueda T, Akagi M, Okada H.

Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin.

Pharmacology research & perspectives 8(4) e00632 2020年8月
Osteosarcoma (OS) is the most common malignant bone tumor and a leading cause of cancer-related deaths in children and adolescents. Current standard treatments for OS are a combination of preoperative chemotherapy, surgical resection, and adjuvant chemotherapy. Cisplatin is used as the standard chemotherapeutic for OS treatment, but it induces various adverse effects, limiting its clinical application. Improving treatment efficacy without increasing the cisplatin dosage is desirable. In the present study, we assessed the combined effect of ascorbate on cisplatin treatment using cultured human OS cells. Co-treatment with ascorbate induced greater suppression of OS cell but not nonmalignant cell proliferation. The chemosensitizing effect of ascorbate on cisplatin treatment was tightly linked to ROS production. Altered cellular redox state due to increased ROS production modified glycolysis and mitochondrial function in OS cells. In addition, OS cell sphere formation was markedly decreased, suggesting that ascorbate increased the treatment efficacy of cisplatin against stem-like cells in the cancer cell population. We also found that enhanced MYC signaling, ribosomal biogenesis, glycolysis, and mitochondrial respiration are key signatures in OS cells with cisplatin resistance. Furthermore, cisplatin resistance was reversed by ascorbate. Taken together, our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

Hashimoto K, Akagi M.

The role of oxidation of low-density lipids in pathogenesis of osteoarthritis: A narrative review

Journal of International Medical Research 48(6) 030006052093160 - 030006052093160 2020年6月
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.

Hashimoto K, Nishimura S, Oka N, Akagi M.

Surgical management of sarcoma in adolescent and young adult patients.

BMC research notes 13(1) 257 - 257 2020年5月26日
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.

Hashimoto K, Nishimura S, Yamagishi K, Tsukamoto I, Nakagawa K, Inoue S, Asada S, Kakinoki R, Akagi M.

Extra-articular synovial osteochondroma of the Hoffa's fat pad involving the patellar tendon: A case report and literature review

Molecular and Clinical Oncology 2020年2月18日

Hashimoto K, Nishimura S, Oka N, Akagi M.

Clinical features and outcomes of primary bone and soft tissue sarcomas in adolescents and young adults

Molecular and Clinical Oncology 2020年2月4日

Otani K, Kakinoki R, Tanaka H, Akagi M.

Delayed rupture of all digital flexor tendons following volar locking plate fixation for distal radius fracture. A case report

Journal of Hand Surgery Asian-Pacific Volume in press 2020年

Hashimoto K, Nishimura S, Akagi M.

Characterization of PD-1/PD-L1 immune checkpoint expression in Osteosarcoma

Diagnostics in press 2020年
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.

Hashimoto K, Nishimura S, Kakinoki R, Akagi M

Soft Tissue Myoepithelioma of the Shoulder: A Case Report

Acta Medica Okayama in press 2020年

Toriumi K, Miyamoto H, Nishimura S, Akagi M.

Radiation-induced osteosarcoma in the cervical spine after definitive radiotherapy for esophageal cancer; a case report

Spine Surgery and Related Research in press 2020年

Hashimoto K, Nishimura S, Oka N, Akagi M.

Outcomes of comprehensive treatment for primary osteosarcoma.

SAGE open medicine 8 2050312120923177 - 2050312120923177 2020年
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.