Faculty Profiles - NISHIDA, Yoshihiro

Papers - NISHIDA, Yoshihiro

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Sustained-release diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate) for knee osteoarthritis: a randomized phase 2 study. Reviewed Open Access

Nishida Y, Kano K, Nobuoka Y, Seo T.

Rheumatology (Oxford) Vol. 60 ( 3 ) page： 1435 - 1444 2021.3

[Ⅰ. Evidence-Based Drug Treatment for Desmoids-Anti-Cancer Drugs, Molecular-Targeted Drugs]. Reviewed

Nishida Y

Gan to kagaku ryoho. Cancer & chemotherapy Vol. 48 ( 3 ) page： 342 - 345 2021.3

Comprehensive molecular and clinicopathological profiling of desmoid tumours Reviewed Open Access

Kohsaka, S; Hirata, M; Ikegami, M; Ueno, T; Kojima, S; Sakai, T; Ito, K; Naka, N; Ogura, K; Kawai, A; Iwata, S; Okuma, T; Yonemoto, T; Kobayashi, H; Suehara, Y; Hiraga, H; Kawamoto, T; Motoi, T; Oda, Y; Matsubara, D; Matsuda, K; Nishida, Y; Mano, H

EUROPEAN JOURNAL OF CANCER Vol. 145 page： 109 - 120 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：European Journal of Cancer

Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56–94.2; p = 8.0 × 10<sup>6</sup>). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.

DOI： 10.1016/j.ejca.2020.12.001

I. Evidence-Based Drug Treatment for Desmoids-Anti-Cancer Drugs. Molecular-Targeted Drugs Reviewed

Nishida Y.

Japanese Journal of Cancer and Chemotherapy Vol. 48 ( 3 ) page： 342 - 345 2021.3

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

Nishida, Y; Ikuta, K; Ito, S; Urakawa, H; Sakai, T; Koike, H; Ito, K; Imagama, S

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Cancer Science

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

DOI： 10.1111/cas.14802

Bone fragility of a school child during COVID-19 Reviewed Open Access

Nishida, Y; Ikuta, K

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Nagoya Journal of Medical Science

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

DOI： 10.18999/nagjms.83.1.217

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

Yamashita K, Kohashi K, Yamada Y, Akatsuka S, Ikuta K, Nishida Y, Toyokuni S, Oda Y.

Genes Chromosomes Cancer. Vol. 60 ( 1 ) page： 26 - 37 2021.1

Clinical Outcome in Soft Tissue Sarcoma Patients with Lung Metastasis Who Received Metastasectomy and/or Radiofrequency Ablation: Tokai Musculoskeletal Oncology Consortium Study Reviewed Open Access

Nakamura, T; Asanuma, K; Takao, M; Yamanaka, T; Koike, H; Chen-Yoshikawa, TF; Tsukushi, S; Kuroda, H; Kozawa, E; Sano, M; Aiba, H; Nakanishi, R; Nagano, A; Yamada, K; Shido, Y; Kawanami, K; Izubuchi, Y; Sudo, A; Nishida, Y

CANCER MANAGEMENT AND RESEARCH Vol. 13 page： 8473 - 8480 2021

Language：English Publishing type：Research paper (scientific journal) Publisher：Cancer Management and Research

Purpose: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions. Methods: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis. Results: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (<11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (<11.5 mm) single metastasis versus 22.7% for patients with larger (>11.5 mm) and multiple metastases. Discussion: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.

DOI： 10.2147/CMAR.S333721

Publisher Correction: Integrated exome and RNA sequencing of dedifferentiated liposarcoma (Nature Communications, (2019), 10, 1, (5683), 10.1038/s41467-019-13286-z) Reviewed Open Access

Hirata M., Asano N., Katayama K., Yoshida A., Tsuda Y., Sekimizu M., Mitani S., Kobayashi E., Komiyama M., Fujimoto H., Goto T., Iwamoto Y., Naka N., Iwata S., Nishida Y., Hiruma T., Hiraga H., Kawano H., Motoi T., Oda Y., Matsubara D., Fujita M., Shibata T., Nakagawa H., Nakayama R., Kondo T., Imoto S., Miyano S., Kawai A., Yamaguchi R., Ichikawa H., Matsuda K.

Nature Communications Vol. 11 ( 1 ) page： 1024 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Communications

The original version of this Article contained an error in Fig. 4, in which samples marked with blue dots were labelled with the suffix ‘WD’ instead of ‘DD’. This has now been corrected in both the PDF and HTML versions of the Article.

DOI： 10.1038/s41467-020-14680-8

Characteristics of primary and repeated recurrent retroperitoneal liposarcoma: outcomes after aggressive surgeries at a single institution Reviewed Open Access

Ishii, K; Yokoyama, Y; Nishida, Y; Koike, H; Yamada, S; Kodera, Y; Sassa, N; Gotoh, M; Nagino, M

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 50 ( 12 ) page： 1412 - 1418 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

Objective: This study sought to investigate the characteristics of primary and repeated recurrent retroperitoneal liposarcoma. Methods: Patients treated with primary or recurrent retroperitoneal liposarcoma between 2005 and 2018 were retrospectively reviewed. Survival time analysis of recurrence-free survival and overall survival was conducted using Kaplan-Meier analysis and log-rank test. Results: Fifty-two patients with primary retroperitoneal liposarcoma were analysed. Amongst them, 46 patients (88%) had undergone surgery. Histologic grades included well-differentiated (n = 21), dedifferentiated (n = 21), myxoid (n = 3) and pleomorphic (n = 1) subtypes. The patients undergoing R0 resection in the first surgery had significantly higher recurrence-free survival rates compared with the patients undergoing non-R0 resection (3-year recurrence-free survival: 80 versus 38%; 5-year recurrence-free survival: 49 versus 29%, P = 0.033). Although overall survival rates tended to be higher in the patients undergoing R0 resection compared with the non-R0 resection, it did not reach to a statistical significant difference (5-year overall survival: 93 versus 75%; 10-year overall survival: 93 versus 59%, P = 0.124). The recurrence rates were 65, 67, 73 and 100%, and the median recurrence-free survival times were 46, 20, 9 and 3 months after the first, second, third and fourth surgeries, respectively. The 5-year overall survival rates were 82, 69, 40 and 0% after the first, second, third and fourth surgeries, respectively. Conclusions: With repeated recurrence and surgeries, the time to recurrence decreased and the recurrence rate increased. R0 resection in the first surgery was considered the most important for longer recurrence-free survival and radical cure.

DOI： 10.1093/jjco/hyaa126

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

Nishida Y, Hamada S, Urakawa H, Ikuta K, Sakai T, Koike H, Ito K, Emoto R, Ando Y, Matsui S.

Cancer Sci. Vol. 111 ( 11 ) page： 4187 - 4194 2020.11

What Factors Are Associated with Treatment Outcomes of Japanese Patients with Clear Cell Chondrosarcoma? Reviewed Open Access

Nakayama, R; Hayakawa, K; Kobayashi, E; Endo, M; Asano, N; Yonemoto, T; Kawashima, H; Hamada, K; Watanabe, I; Futani, H; Goto, T; Nishida, Y; Ozaki, T

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Vol. 478 ( 11 ) page： 2537 - 2547 2020.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical Orthopaedics and Related Research

BackgroundClear cell chondrosarcoma is an extremely rare chondrosarcoma subtype; thus, its treatment outcomes and associated factors have not been widely studied. Knowing more about it is potentially important because clear cell chondrosarcomas are often misdiagnosed as other benign lesions and subsequently treated and followed inappropriately.Questions/purposes(1) What are the patient- and tumor-related characteristics of clear cell chondrosarcoma? (2) What proportion of patients with clear cell chondrosarcoma initially had a misdiagnosis or a misleading initial biopsy result? (3) What is the survivorship of patients with clear cell chondrosarcoma free from death, local recurrence, and distant metastasis, and what factors are associated with greater survivorship or a reduced risk of local recurrence?MethodsBetween 1985 and 2018, 12 Japanese Musculoskeletal Oncology Group (JMOG) hospitals treated 42 patients with a diagnosis of clear cell chondrosarcoma. All 42 patients had complete medical records at a minimum of 1 year or death, and were included in this multicenter, retrospective, observational study. No patients were lost to follow-up within 5 years of treatment but four were lost to follow-up greater than 5 years after treatment because their physicians thought their follow-up was sufficient. Clinical data were collected by chart review. The median (range) follow-up period was 69 months (2 to 392). In general, when a possibly malignant bone tumor was found on imaging studies, the histological diagnosis was made by biopsy before initiating treatment. Once the diagnosis had been made, the patients were treated by surgery only, complete resection if technically possible, because chondrosarcomas are known to be resistant to chemotherapy and radiotherapy. Unresectable tumors were treated with particle-beam radiation therapy. When patients with chondrosarcoma were referred after unplanned surgical procedures with inadequate surgical margins, immediate additional wide resection was considered before local recurrence developed. This diagnostic and treatment strategy is common to all JMOG hospitals and did not change during the study period. Primary wide resection was performed in 79% (33 of 42) patients, additional wide resection after initial inadequate surgery in 12% (five of 42), curettage and bone grafting in 5% (two of 42) patients, and radiotherapy was administered to 5% (two of 42). Surgical margins among the 40 patients who underwent surgery at JMOG hospitals were no residual tumor in 93% (37 of 42) of patients, microscopic residual tumor in 2% (one of 42), and macroscopic residual tumor or state after curettage or intralesional excision in 5% (two of 42). The oncological endpoints of interest were 5- and 10- year overall survival, disease-free survival, survival free of local recurrence, and survival free of distant metastases; these were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk ratios with their respective 95% confidence intervals (CIs) were estimated in a Cox regression model. The Bonferroni adjustment was used for multiple testing correction.ResultsThe sex distribution was 74% men and 26% women (31 and 11 of 42, respectively), with a mean age of 47 ± 17 years. Eighty one percent (34 of 42) of tumors occurred at the ends of long bones, and the proximal femur was the most common site accounting for 60% (25 of 42). The mean size of the primary tumors was 6.3 ± 2.7 cm. Definite pathologic fractures were present in 26% (10 of 42) and another 26% (10 of 42) had extraskeletal involvement. None had metastases at presentation. Twenty four percent (six of 25) tumors in the proximal femur were misdiagnosed as benign lesions and treated inadequately without biopsy. Twenty nine percent (10 of 35) patients had initial misdiagnoses by biopsy and core needle biopsies had a greater risk of resulting in inaccurate histological diagnoses. The study patients' 5- and 10-year overall survival rates were 89% (95% CI 74 to 96) and 89% (95% CI 74 to 96), respectively; 5- and 10- year disease-free survival rates 77% (95% CI 58 to 89) and 57% (95% CI 36 to 75), respectively; 5- and 10-year local recurrence-free survival rates 86% (95% CI 68 to 95) and 71% (95% CI 49 to 86), respectively; and 5- and 10-year distant metastasis-free survival rates 84% (95% CI 67 to 93) and 74% (95% CI 53 to 88), respectively. Notably, bone metastases (17%, seven of 42) were as common as pulmonary metastases (14%, six of 42); four patients developed both bone and pulmonary metastases. The difference between 10-year overall survival rates and 10-year disease-free survival indicated very late recurrence more than 5 years after the initial treatment. After controlling for multiple comparisons, the only factor we found that was associated with local recurrence-free survival was initial treatment (positive margin versus primary wide resection) (risk ratio 8.83 [95% CI 1.47 to 53.1]; p = 0.022 after the Bonferroni adjustment). Additional wide resection reduced the risk of local recurrence.ConclusionsThe femoral head was the most common location of clear cell chondrosarcoma and had a high risk of misdiagnosis as common benign lesions that resulted in initial inadequate surgery and a consequent high risk of local recurrence. Immediate additional wide resection should be considered in patients who had initial inadequate surgery to reduce the risk of local recurrence. Because clear cell chondrosarcoma can recur locally or distantly in the bones and lungs in the long term, patients should be informed of the risk of very late recurrence and the necessity of decades-long with surveillance for local recurrence and lung and bone metastases.Level of EvidenceLevel IV, therapeutic study.

DOI： 10.1097/CORR.0000000000001266

Forced expression of KIAA1199, a novel hyaluronidase, inhibits tumorigenicity of low-grade chondrosarcoma Reviewed Open Access

Koike, H; Nishida, Y; Shinomura, T; Zhuo, LS; Hamada, S; Ikuta, K; Ito, K; Kimata, K; Ushida, T; Ishiguro, N

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Orthopaedic Research

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

DOI： 10.1002/jor.24629

Is tumour location a prognostic factor for pharmacological treatment in patients with desmoid-type fibromatosis? a systematic review Reviewed Open Access

Koike, H; Hamada, S; Sakai, T; Shimizu, K; Yoshida, M; Nishida, Y

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 50 ( 9 ) page： 1032 - 1036 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

Background: The mainstay of the treatment for desmoid-type fibromatoses has been shifting from surgery to drug treatment, making accurate prediction of the efficacy of drug treatment of extreme importance. On the other hand, desmoid-type fibromatoses arise everywhere in the body. The purpose of this systematic review was to address the clinical question of whether tumour location has an impact on the efficacy of drug treatment. Methods: A literature search from January 1990 to August 2017 was conducted. Four reviewers independently assessed and screened the literature for eligibility and determined the final articles. They rated each report according to the Grading of Recommendations Development and Evaluation approach. Based on the quality of 'Body of Evidence', our clinical guideline committee developed a recommendation for the clinical question. Results: In total, 128 articles were extracted. After the screenings, 5 were chosen for the final evaluation. The drugs used in these articles were one each of toremifene, sorafenib, and methotrexate and vinblastine and of meloxicam. There were no randomized controlled trials, and two prospective and three retrospective case series were included. Therapeutic effects were observed slightly more markedly in extremity using meloxicam or methotrexate and vinblastine. In contrast, the efficacy of toremifene was slightly higher in non-extremity. However, the evidence level of all of the reports was judged to be low. Conclusions: Considering the low evidence level, we concluded that the site-specific therapeutic effects of drugs could not be confirmed in desmoid-type fibromatoses.

DOI： 10.1093/jjco/hyaa078

Is mutation analysis of β-catenin useful for the diagnosis of desmoid-type fibromatosis? A systematic review Reviewed Open Access

Sakai, T; Hamada, S; Koike, H; Shimizu, K; Yoshida, M; Nishida, Y

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 50 ( 9 ) page： 1037 - 1042 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

Background: An accurate diagnosis is crucial to determine the treatment modality for desmoid-type fibromatosis, although the histopathological diagnosis is occasionally difficult to make. Many desmoid-type fibromatosis have been reported to have hotspot mutation of β-catenin gene (CTNNB1). In the present study, we performed a systematic review to verify the usefulness of CTNNB1 mutation analysis in the diagnosis of desmoid-type fibromatosis. Methods: A literature search from January 1990 to August 2017 was conducted. Three reviewers independently assessed and screened the literature for eligibility and determined the final articles to be evaluated. Data regarding the sensitivity, specificity, accuracy and usefulness of CTNNB1 mutation analysis in the diagnosis of desmoid-type fibromatosis were recorded. We rated each report according to the Grading of Recommendations Development and Evaluation approach. Results: The search yielded 90 studies, seven of which were included after the first and second screenings. The positive rate of CTNNB1 mutation in desmoid-type fibromatosis was 86.8%, but the cohort of six of the seven reports was already diagnosed histopathologically as desmoid-type fibromatosis. Therefore, the usefulness of CTNNB1 mutation analysis in a cohort that is difficult to diagnose histopathologically is not clear in this review. Nevertheless, CTNNB1 mutation showed very high specificity in desmoid-type fibromatosis, indicating the usefulness of CTNNB1 mutation analysis in its diagnosis in combination with histological examination. Conclusion: Because the lack of data precludes any useful comparison with histological diagnosis, the evidence level is low. However, considering its specificity, CTNNB1 mutation analysis may be useful in cases in which the histopathological diagnosis is difficult.

DOI： 10.1093/jjco/hyaa080

Short physical performance battery discriminates clinical outcomes in hospitalized patients aged 75 years and over Reviewed

Fujita, K; Nakashima, H; Kako, M; Shibata, A; Cheng, YT; Tanaka, S; Nishida, Y; Kuzuya, M

ARCHIVES OF GERONTOLOGY AND GERIATRICS Vol. 90 page： 104155 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Archives of Gerontology and Geriatrics

Aim: Low physical function is associated with poor outcomes in hospitalized patients; however, little is known about vulnerable populations such as those aged ≥ 75 years. We examined whether the Short Physical Performance Battery (SPPB) was associated with clinical outcomes in hospitalized patients aged ≥ 75 years. Methods: In total, 147 patients aged ≥ 75 years (mean age, 86.5 ± 4.7 years; 89 males) completed the SPPB and Mini-Mental State Examination (MMSE) before hospital discharge. Patients were divided into three groups by SPPB score: 0 (unable to perform SPPB), 1–6 (low performance), and 7–12 (high performance). The first occurrence of all-cause unplanned readmission or all-cause mortality within 1 year after discharge was set as the endpoint. Results: The median SPPB score of the study population was 2; 41 % were unable to perform SPPB, 33 % had low performance, and 26 % had high performance. High SPPB was associated with younger age, higher body weight, and higher MMSE score. During the follow-up period, 35 (23.8 %) patients were readmitted to hospital and 19 (12.9 %) died. Even after adjusting for covariates, SPPB score was a significant and independent predictor of poor outcomes (hazard ratio for 1 point increase in SPPB, 0.88; P = .002). The subgroup analysis showed SPPB was inversely associated with the occurrence of poor outcomes in patients with cognitive impairment. Conclusions: SPPB is inversely associated with risks for readmission and mortality in hospitalized patients aged ≥ 75 years, especially those with cognitive impairment. The present results indicate the SPPB is useful for accurate prognosis in hospital settings.

DOI： 10.1016/j.archger.2020.104155

Cardiac metastases from primary myxoid liposarcoma of the thigh: a case report Reviewed Open Access

Ikuta, K; Sakai, T; Koike, H; Okada, T; Imagama, S; Nishida, Y

WORLD JOURNAL OF SURGICAL ONCOLOGY Vol. 18 ( 1 ) page： 227 2020.8

Language：English Publishing type：Research paper (scientific journal) Publisher：World Journal of Surgical Oncology

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

DOI： 10.1186/s12957-020-02009-0

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

Makida, K; Nishida, Y; Morita, D; Ochiai, S; Higuchi, Y; Seki, T; Ikuta, K; Ishiguro, N

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Deficiency of vitamin D is an important cause of osteosarcopenia. The purpose of this study is to examine the effects of low energy narrow-range UV-LED on osteosarcopenia in animal models of senescence-accelerated mouse prone 6 (SAMP6). Preliminary experiments specified the minimum irradiance intensity and dose efficacy for vitamin D production (316 nm, 0.16 mW/cm<sup>2</sup>, 1,000 J/m<sup>2</sup>). we set a total of 4 groups (n = 8 per group); vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-repletion with UV irradiation (Vit.D+UV +), vitamin D-deficiency without UV irradiation, (Vit.D−UV−), and vitamin D-deficiency with UV irradiation (Vit.D−UV +). Serum levels of 25(OH)D at 28 and 36 weeks of age were increased in Vit.D−UV+ group as compared with Vit.D−UV− group. Trabecular bone mineral density on micro-CT was higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. In the histological assay, fewer osteoclasts were observed in Vit.D−UV+ group than in Vit.D−UV− group. Grip strength and muscle mass were higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. Signs of severe damage induced by UV irradiation was not found in skin histology. Low energy narrow-range UV irradiation may improve osteosarcopenia associated with vitamin D deficiency in SAMP6.

DOI： 10.1038/s41598-020-68641-8

Functional evaluation following deltoid muscle resection in patients with soft tissue sarcoma Reviewed Open Access

Hamada, S; Nishida, Y; Takanari, K; Ota, T; Urakawa, H; Ikuta, K; Sakai, T; Tsukushi, S; Kamei, Y; Ishiguro, N

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

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

DOI： 10.1093/jjco/hyaa039

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

Urakawa, H; Ando, Y; Hase, T; Kikumori, T; Arai, E; Maeda, O; Mitsuma, A; Sugishita, M; Shimokata, T; Ikuta, K; Ishiguro, N; Nishida, Y

INTERNATIONAL JOURNAL OF CANCER Vol. 146 ( 12 ) page： 3504 - 3515 2020.6

Language：English Publishing type：Research paper (scientific journal) Publisher：International Journal of Cancer

Bone modifying agents (BMAs) have become a standard treatment to prevent skeletal-related events (SREs) in bone metastases (BMs). The aim of our study is to determine the clinical value of serum bone resorption markers for predicting clinical outcomes after using BMAs in patients with BM. Patients were enrolled between May 2013 and October 2017 at the Nagoya University Hospital, Japan. We prospectively observed changes in pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) during treatment with BMAs. The relationship between serum markers before and after treatment and clinical outcomes such as progression of bone disease (BD), SREs and overall survival (OS) were evaluated. Pearson chi-square test and Kaplan–Meier product limit methods were used for analysis. Sixty-seven patients were analyzed. The primary tumor sites were 21 lung, 16 breast and 30 others. Forty and 27 patients were treated with Denosumab and Zoledronic acid, respectively. Progression of BDs, SREs and death were observed in 10, 16 and 31 cases, respectively. The median follow-up period after using BMAs was 12.3 (range 0.3–66.3) months. ICTP at 3–4 weeks was significantly correlated with increasing BD progression, SREs and death after treatment in both the whole and lung cancer cohorts. Base line ICTP and TRACP-5b were also associated with increasing BD progression in the whole cohort. Our study showed that early posttreatment ICTP is useful for predicting BD progression, SREs and OS after use of BMAs in patients with BM and even in patients with lung cancer BM.

DOI： 10.1002/ijc.32836

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