Faculty Profiles - NISHIDA, Yoshihiro

Effectiveness of introducing a health care application for prehabilitation in patients undergoing major hepatobiliary-pancreatic surgery: a pilot study Reviewed

Nagaya, M; Yokoyama, Y; Mizuno, Y; Nakajima, H; Inoue, T; Tanaka, S; Yano, R; Hayashi, N; Nishida, Y; Ebata, T

SURGERY TODAY Vol. 56 ( 3 ) page： 283 - 292 2026.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Surgery Today

Purpose: Prehabilitation is known to improve outcomes of gastrointestinal surgery; however, the issue of low adherence during the waiting period for surgery remains unresolved. This study evaluated the effectiveness and feasibility of a newly developed mobile health application, “Preha,” designed to support home-based prehabilitation. Methods: A single-group pilot study involving patients scheduled for major hepatobiliary-pancreatic (HBP) surgery for malignancy between March 2023 and September 2024 was conducted. The patients downloaded the Preha application, and there was no direct intervention from the medical staff during the preoperative period. The application recorded step counts, moderate-intensity exercise times, and squat counts. Adherence was defined as meeting at least one of the following: ≥ 5,000 steps/day, ≥ 10 min/day of ≥ 3 METS activities, or ≥ 30 squats/day, for more than three days per week. Results: Among 30 eligible patients, 21 (median age, 67 years) were included in the analysis. During prehabilitation, 52% achieved the step goal, 67% met the exercise time target, and 33% completed the squat goal. Conclusions: The “Preha” application facilitated good adherence to home-based prehabilitation without direct intervention, indicating its feasibility and potential as a perioperative support tool for patients undergoing HBP surgery. Trial registration https://jrct.niph.go.jp/; registration number: jRCTs042220106.

DOI： 10.1007/s00595-025-03124-9

Clinical outcome of patients with soft tissue sarcoma after bone metastases: Tokai musculoskeletal oncology consortium study Reviewed

The utility of apparent diffusion coefficient maps for evaluating chemotherapy response and prognosis in osteosarcoma Reviewed Open Access

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

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 31 ( 2 ) page： 456 - 465 2026.3

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

Background: Assessing the response to neoadjuvant chemotherapy is crucial for determining surgical treatment strategies and optimizing personalized postoperative care in osteosarcoma patients. The apparent diffusion coefficient, derived from diffusion-weighted imaging, reflects tumor aggressiveness; however, its role in evaluating neoadjuvant chemotherapy response remains unclear. This study aimed to evaluate the utility of apparent diffusion coefficient maps in assessing chemotherapy-induced necrosis and prognosis in osteosarcoma. Methods: Twenty osteosarcoma patients referred to our hospital between 2007 and 2020, for whom apparent diffusion coefficient maps were available, were included. The association between apparent diffusion coefficient values, tumor necrosis rate, and prognosis was analyzed. Results: The study cohort consisted of 14 males and six females, with a median age of 16 years (range, 7–37). Tumor locations included the femur (12 patients), tibia (5), humerus (2), and scapula (1). Significant correlations were found between changes in mean apparent diffusion coefficient values pre- and post-neoadjuvant chemotherapy and tumor necrosis rate (r = 0.61, p < 0.01). Post-chemotherapy mean and minimum apparent diffusion coefficient values were significantly associated with overall survival (p = 0.04 for both). Conclusions: This study demonstrates a strong correlation between chemotherapy effectiveness and apparent diffusion coefficient values in osteosarcoma. Future clinical efforts should focus on integrating apparent diffusion coefficient values into treatment strategies to improve patient outcomes.

DOI： 10.1016/j.jos.2025.07.006

Fatal Pericarditis and Cardiac Tamponade During Selumetinib Treatment for Pericardial Neurofibroma Reviewed Open Access

Sato, S; Koguchi-Yoshioka, H; Yokoi, K; Nabeshima, R; Matsui, T; Morii, E; Fujimoto, M; Nishida, Y; Wataya-Kaneda, M

JOURNAL OF DERMATOLOGY 2026.2

Real-world outcomes for selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas in Japan: A 1-year interim analysis Reviewed Open Access

Nishida, Y; Kitajima, A; Ishii, T

NEURO-ONCOLOGY ADVANCES Vol. 8 ( 1 ) page： vdag042 2026.1

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Neuro Oncology Advances

Background This postmarketing surveillance assessed the real-world safety and effectiveness of selumetinib in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) in Japan. Methods The surveillance was initiated on November 16, 2022, the launch date of selumetinib in pediatric indication in Japan. All patients treated with selumetinib were eligible for enrollment. The observation period was set to 3 years from drug initiation (data cutoff for 1-year analysis: October 9, 2024). Patient characteristics and safety and effectiveness data were captured using case report forms. Results In total, 52 patients were included in the analysis (median [range] age, 13.0 [5–20] years; age <19 years, 49 [94.2%] patients; female, 28 [53.8%] patients; dermatological, neurological, and bone manifestations [DNB] classification stage 5, 30 [57.7%] patients; median disease duration [N = 49], 118.0 months). The median treatment duration was 52.1 weeks, and 46 (88.5%) patients were on selumetinib treatment at 1 year. Adverse drug reactions (ADRs) and serious ADRs were observed in 46 (88.5%) and 9 (17.3%) patients, respectively. The most common ADRs were diarrhoea (28.8%), dermatitis acneiform (26.9%), blood creatine phosphokinase increased (23.1%), and paronychia (19.2%). No fatal ADRs were reported. The median time to the first onset of any ADR was 0.492 months. Investigator’s assessment, target PN size on imaging, patient’s general self-assessment, and performance status generally indicated the effectiveness of selumetinib. Conclusions The safety profile of selumetinib was generally consistent with the findings of the phase 2 SPRINT trial and Japanese phase 1 trial. No new safety concerns were identified.

DOI： 10.1093/noajnl/vdag042

A transformative perspective in orthopaedic oncology for patients’ futures Invited Reviewed

Nishida Y.

Journal of Orthopaedic Science 2026

Meflin is a druggable target using antibody-drug conjugates in progressive osteosarcoma Reviewed Open Access

Esaki, N; Sakoda, T; Ando, R; Miyai, Y; Iida, T; Mizutani, Y; Yoshida, M; Hara, Y; Matsuyama, M; Kobayashi, T; Shiraki, Y; Mii, S; Ichikawa, J; Kawasaki, T; Manabe, S; Sakai, T; Nishida, Y; Takahashi, M; Enomoto, A

ONCOGENE Vol. 44 ( 47 ) page： 4576 - 4586 2025.12

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

The 5-year overall survival rate of patients with recurrent osteosarcoma (OS) has remained less than 30%, which is attributed to the persistence and growth of OS cells with high chemoresistance, tumorigenicity and metastatic potential. However, the characteristics of recurrent OS cells and therapeutic strategies remain unexplored. In the present study, we found that Meflin, a membrane protein previously identified as a specific marker of mesenchymal stromal/stem cells, was highly expressed in tumor cells of patients with progressive OS. Interestingly, OS cells resistant to doxorubicin showed upregulated Meflin expression and high tumorigenicity. Meflin expression was correlated with that of cancer stem cell markers such as multidrug resistance-associated protein 1. In addition, Meflin is involved in bone morphogenetic protein signaling by binding to its cognate receptor and regulating anchorage-independent sphere formation in OS cells. This suggests that Meflin expression may be associated with the acquisition of tumor-initiating or stem-like features. We generated antibody-drug conjugates (ADCs) consisting of anti-Meflin antibodies covalently linked to the cytotoxic agent monomethyl auristatin E (anti-Meflin ADCs). Anti-Meflin ADCs were internalized and exhibited remarkable cytotoxicity in cultured Meflin-positive OS cells and antitumor efficacy in OS murine models. Importantly, they did not show any obvious adverse effects in wild-type mice. Collectively, these data provide evidence that anti-Meflin ADCs warrant further development as novel therapeutic targets for Meflin-positive refractory or recurrent OS.

DOI： 10.1038/s41388-025-03605-8

Hagi, T; Nakamura, T; Tsukushi, S; Koike, H; Kimura, H; Nagano, A; Hosono, K; Shido, Y; Kozawa, E; Kawanami, K; Asanuma, K; Matsuyama, Y; Hasegawa, M; Nishida, Y

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 55 ( 11 ) page： 1253 - 1258 2025.11

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

Background Soft tissue sarcomas (STSs) are a diverse group of rare malignant tumors accounting for <1% of all human tumors. Almost 50% of patients with STS develop metastatic disease, mainly within 3 years of initial diagnosis. Lung metastasis occurs in 20%-30% of STS cases, while bone metastasis is rare. Patients and methods We investigated tumor characteristics and clinical outcomes in 59 patients with STS who developed bone metastases. Results A total of 21 patients had solitary bone metastasis: two in the extremity, 11 in the vertebral body, and eight in the trunk. Around 38 patients had multiple bone metastases: 18 with extremity bone involvement and 20 with no extremity bone involvement. Fourteen patients developed complicated bone metastases with distant extrapulmonary metastases. Seven patients had no distant metastases other than bone; that is, the bone was the first distant metastasis. The 5-year disease-specific survival (DSS) rate after primary treatment was 45.1%. The median 5-year DSS after bone metastasis was 28.1 months. The 5-year DSS rate was 55.6% in nine patients who underwent radical local treatment for solitary bone metastases. The 5-year DSS rate was 14.7% in 50 patients who did not undergo local radical treatment for bone metastases, with a significant correlation. Conclusion Patients with bone metastases from STS had a relatively good prognosis after bone metastases. Solitary bone metastases can be aggressively treated. Although nearly half of the patients received bone-modifying agents, the effectiveness of these therapeutics warrants further investigation.

DOI： 10.1093/jjco/hyaf121

Long-term functional and quality of life outcomes after cementless minimally invasive extendable endoprosthesis replacement in skeletally immature patients with bone sarcomas at the lower limb a Japanese Musculoskeletal Oncology Group (JMOG) study Reviewed Open Access

Voriconazole-induced periostitis in a child with finger pain and nodules: case report and literature review Reviewed Open Access

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

BMC MUSCULOSKELETAL DISORDERS Vol. 26 ( 1 ) page： 779 2025.8

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Musculoskeletal Disorders

Background: Voriconazole-induced periostitis is predominantly reported in adults, with pediatric cases being exceedingly rare. Case presentation: This report describes an 8-year-old boy with voriconazole-induced periostitis presenting with finger pain and nodules, initially suspected to be bone tumors. The patient had been on voriconazole for two years and seven months to treat Aspergillus pneumonia and had been hospitalized for six months due to chronic graft-versus-host disease following hematopoietic stem cell transplantation and total body irradiation for severe congenital neutropenia. The patient presented with a five-month history of pain and a one-month history of a mass in the middle finger of his right hand. Radiographs revealed bone formation outside the cortical bone in the proximal phalanx of the right middle finger and the distal ulna. Differential diagnoses included benign bone-forming tumors, such as osteochondroma post-total body irradiation, and bizarre parosteal osteochondromatous proliferation. The diagnosis of voriconazole-induced periostitis was confirmed as new sites of periostitis became apparent during the disease course. Conclusions: Voriconazole-induced periostitis should be considered, even in pediatric patients, when multiple nodular periosteal reactions are observed in immunosuppressed patients undergoing long-term voriconazole therapy.

DOI： 10.1186/s12891-025-09059-z

特集遺伝カウンセリングを学ぼう! Ⅱ.様々な場面での遺伝カウンセリング神経線維腫症1型 Reviewed

森川真紀, 城所博之, 西田佳弘

小児科診療 Vol. 88 ( 8 ) page： 995 - 1000 2025.8

Tsuda, Y; Nishida, Y; Sakamoto, A; Ogura, K; Fujiwara, T; Sekita, T; Kawano, H; Kobayashi, H

BONE & JOINT OPEN Vol. 6 ( 8 ) page： 954 - 963 2025.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Bone and Joint Open

Aims Extendable endoprostheses are utilized to reconstruct segmental defects following resection of bone sarcomas in skeletally immature children. However, there remains a paucity of data regarding long-term functional and quality of life outcomes. Methods We conducted a retrospective, multicentre study and reviewed 45 children who underwent cementless minimally invasive extendable endoprosthetic replacement. Anatomical sites included the distal femur (n = 29), proximal femur (n = 4), proximal tibia (n = 11), and total femur (n = 1). The mean follow-up period was 12 years. The mean age at extendable endoprosthetic replacement was ten years (5 to 15). Most patients (96%, 43/45) had reached skeletal maturity at the final follow-up. Results The ten-year endoprosthetic failure-free survival rate was 60%. Of the 45 patients, 25 (56%) had 42 complications which were frequently related to structural failure (45%, 19/42), with extension mechanism jamming being the most common (n = 7, 17%). Excluding length-ening procedures, 20 patients (44%) underwent additional surgery with a mean of two surgeries per patient. The mean limb-length discrepancy at the final follow-up was 2.3 cm. Limb salvage was achieved in 44 (98%) patients. The mean Musculoskeletal Tumor Society (MSTS) scores, Toronto Extremity Salvage Score (TESS), and EuroQol five-dimension five-level questionnaire (EQ-5D-5L) were 78%, 92%, and 92% at the last follow-up, respectively. Multiple additional surgeries (≥ 2 times) for complications were associated with worse MSTS scores compared with those without multiple additional surgeries (p = 0.009). Moreover, limb-length discrepancy > 3 cm showed significantly worse MSTS scores compared with those ≤ 3 cm (p = 0.019). Conclusion Extendable endoprostheses were associated with a high complication rate and need for additional surgeries over time, especially for structural-related complications. Despite this, successful limb salvage with reasonable function/quality of life and small limb-length discrepancy were achievable in the long term. Patients’ function in the long term depended on the experience of postoperative complications and limb-length discrepancy.

DOI： 10.1302/2633-1462.68.BJO-2025-0062.R1

Prognostic value of symptom burden as a simple patient-reported outcome measure in older patients with heart failure Reviewed Open Access

Tanaka, S; Imaizumi, T; Morohashi, A; Kobayashi, K; Takagi, D; Hattori, K; Yoshito, N; Takeuchi, S; Tsuchikawa, Y; Inoue, T; Nagaya, M; Nishida, Y; Morimoto, R; Kondo, T; Hiraiwa, H; Kazama, S; Okumura, T; Murohara, T

SCIENTIFIC REPORTS Vol. 15 ( 1 ) page： 22954 2025.7

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

This study was performed to investigate the prognostic value of assessing symptom burden using the Edmonton Symptom Assessment System (ESAS) in older patients with Heart Failure (HF). This prospective cohort study was performed in consecutive patients ≥ 60 years old hospitalized with HF at a university hospital between September 2020 and June 2023. ESAS was used to assess nine common symptoms at hospital discharge (total score: 0–90) with higher scores indicating greater severity. The primary outcome was the combined event of HF readmission and all-cause mortality within 6 months. The median ESAS sum score in the study population consisting of 306 patients (median age, 79 years; 54.9% male) was 13 points. The commonly reported moderate-to-severe symptoms were impaired well-being (34.9%), anxiety (27.5%), drowsiness (25.8%), tiredness (24.9%), and depression (22.2%). In multivariate analyses, ESAS sum score was significantly associated with the combined event (adjusted hazard ratio for each 5-point increase, 1.10 (95% confidence interval: 1.04–1.17; p < 0.001). Inclusion of ESAS sum score in the risk model significantly increased both continuous net reclassification improvement (p = 0.028) and integrated discrimination improvement (p = 0.002) for the primary outcome. Comprehensive assessment of symptom burden with ESAS provided additional prognostic information to conventional risk factors in older patients with HF.

DOI： 10.1038/s41598-025-06615-4

Natural course of patients diagnosed with nodular fasciitis Reviewed Open Access

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

BMC MUSCULOSKELETAL DISORDERS Vol. 26 ( 1 ) page： 581 2025.7

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Musculoskeletal Disorders

Background: Nodular fasciitis (NF) shrinks spontaneously; however, few reports have focused on its self-regression. This study investigated NF shrinkage. Methods: We retrospectively reviewed 55 patients with NF who visited Nagoya University Hospital. Twenty-three patients were followed-up and evaluated for shrinkage. Factors affecting the occurrence of deep layers and ≥ 50% tumor volume shrinkage were investigated. The proportion of patients who achieved ≥ 50% tumor volume shrinkage, time to ≥ 50% tumor volume shrinkage, and tumor volume compared with baseline at the last follow-up were assessed. Results: The presence of deep layers was significantly associated with longer symptom duration and more frequent biopsies. The proportion of patients who achieved ≥ 50% tumor volume shrinkage, time to ≥ 50% tumor volume shrinkage, and tumor volume compared to baseline at the last follow-up were 17 of 23 patients (74%), median 104 days (19–973)days, and median 24% (7–99%), respectively. Shorter duration of symptoms was significantly associated with ≥ 50% tumor volume shrinkage. Conclusion: Approximately three-quarters of the patients demonstrated ≥ 50% tumor volume shrinkage, suggesting that wait-and-see concept was acceptable for NF. The better understanding of NF shrinkage showed that proper follow-up is necessary for patients with NF.

DOI： 10.1186/s12891-025-08895-3

Efficacy and safety of selumetinib in adults with neurofibromatosis type 1and symptomatic, inoperable plexiform neurofibromas (KOMET): a multicentre, international, randomised, placebo-controlled, parallel, double-blind, phase 3 study Reviewed

Chen, AP; Coyne, GO; Wolters, PL; Martin, S; Farschtschi, S; Blanco, I; Chen, ZP; Darrigo, LG Jr; Eoli, M; Whittle, JR; Nishida, Y; Lamarca, R; Rodriguez, RD; Adeyemi, A; Herrero, I; Llorente, N; Diede, S; Dombi, E; Wolkenstein, P

LANCET Vol. 405 ( 10496 ) page： 2217 - 2230 2025.6

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

Background: Currently, no worldwide approved therapies exist for adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas. The KOMET study aimed to evaluate selumetinib (ARRY-142886, AZD6244) efficacy and safety in this population. Methods: This ongoing multicentre, international, randomised, placebo-controlled, phase 3, parallel, double-blind trial randomly assigned adults with NF1-plexiform neurofibroma 1:1 to 28-day cycles of oral selumetinib 25 mg/m2 twice daily, or placebo with crossover to selumetinib at confirmed radiological progression or the end of cycle 12. The primary endpoint was objective response rate (confirmed partial or complete response) established by use of independent central review per Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria by cycle 16 (selumetinib vs placebo). This study (KOMET) is registered with ClinicalTrials.gov, NCT04924608 and is ongoing. Findings: Overall, of 184 participants enrolled, 145 adults were randomly assigned to selumetinib (n=71) or placebo (n=74). Selumetinib led to a rapid response (median 3·7 months), with an objective response rate of 20% (n=14/71; 95% CI 11·2 to 30·9) by cycle 16 versus 5% (n=4/74; 1·5 to 13·3) with placebo (p=0·011). Participants with baseline chronic pain intensity scores of at least 3 had a greater reduction in score at cycle 12 with selumetinib versus placebo (least-squares mean [SE] −2·0 [0·30] −2·6 to −1·4, vs −1·3 [0·29] −1·8 to −0·7; p=0·070), although this did not reach significance; and a clinically meaningful improvement from baseline. Change from baseline to cycle 12 in PlexiQoL total scores between treatment groups was not significant (least-squares mean difference [SE] −0·1 [0·59]; −1·2 to 1·1). Adverse events were consistent with the known selumetinib safety profile. Interpretation: In the first international, randomised, placebo-controlled trial in adults with NF1-plexiform neurofibromas, selumetinib achieved a significant objective response rate versus placebo. No new safety concerns were identified. The observations of reduction in tumour volume by cycle 16, reduction in chronic and spike pain, reduction in analgesia, and decrease in pain interference over placebo show that selumetinib is effective at treating plexiform neurofibromas in adults with NF1. Funding: AstraZeneca as part of an alliance between AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck, Rahway, NJ, USA.

DOI： 10.1016/S0140-6736(25)00986-9

Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): Primary analysis of KOMET (NCT04924608), a phase 3, international, randomized, placebo-controlled study Reviewed Open Access

Functional analysis and the importance of ligament reconstruction after soft tissue sarcoma surgery around the knee joint -a Tokai musculoskeletal oncology consortium study Reviewed Open Access

Koike, H; Ikuta, K; Nagano, A; Aiba, H; Asanuma, K; Hamada, S; Kozawa, E; Izubuchi, Y; Kawanami, K; Imagama, S; Nishida, Y

WORLD JOURNAL OF SURGICAL ONCOLOGY Vol. 23 ( 1 ) page： 236 2025.6

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

Background: Surgery for soft tissue sarcoma (STS) around the knee joint often requires extensive tissue resection, leading to significant functional impairment. This study aimed to evaluate knee function following surgery for STS around the knee joint and to assess the importance of ligament reconstruction in cases where the collateral ligaments were excised. Methods: We included 63 patients treated surgically at eight hospitals participating in the Tokai Musculoskeletal Oncology Consortium between 2008 and 2019. Tumor development within 3 cm proximal to the superior patella and 3 cm distal to the tibial articular surface was defined as the area surrounding the knee joint. The median patient age was 61 years (25 males; median follow-up period, 62 months). The median tumor size was 60 mm. The histological types included 18 undifferentiated pleomorphic sarcomas (UPS), 17 myxoid liposarcomas, 7 myxofibrosarcomas (MFS), and 21 others. Knee function was assessed using the Lysholm score. Results: The 5-year overall survival rate was 91%. Factors significantly associated with lower Lysholm scores were female sex (p = 0.01), tumor histology such as MFS and UPS (p = 0.01), adductor muscle resection (p < 0.001), lateral collateral ligament (LCL) resection (p = 0.002), patellar tendon resection (p = 0.019), and medial collateral ligament (MCL) resection (p = 0.024). The group with ≥ 4 resected muscles had significantly lower Lysholm scores than the group with < 4 resected muscles (p = 0.003). Multivariate analysis showed that the factors significantly associated with lower Lysholm scores were adductor muscle resection, female sex, and tumor histology (MFS and UPS). Among patients who required excision of the LCL or MCL, those who underwent ligament reconstruction had better functional scores than those who did not (p = 0.06). Conclusions: This study identified factors that significantly affected post-resection function in patients with STS of the knee joint. These findings may assist in predicting postoperative function after STS surgery around the knee joint, suggesting that ligament reconstruction may give a suggestive benefit for improving the function in cases requiring resection of the LCL or MCL.

DOI： 10.1186/s12957-025-03891-2

Oncological Outcomes and Postoperative Complications for Localized Soft Tissue Sarcomas of the Extremities and Trunk Wall in Patients Aged 85 Years or Older Reviewed Open Access

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

CANCERS Vol. 17 ( 12 ) 2025.6

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

Objectives: The management of soft tissue sarcoma in patients aged ≥ 85 years remains a clinical dilemma, as evidence to guide treatment decisions in this population is limited. Here, we aimed to compare the clinical characteristics of patients aged ≥ 85 years who underwent surgery with those who did not, to identify factors influencing surgical decision-making. We also assessed the oncological outcomes and postoperative complications in the patients. Methods: We reviewed 37 consecutive patients with localized disease involving either the extremities or trunk wall, with a median age of 89.0 years. No significant differences in demographics or clinical characteristics were observed between patients who underwent surgery and those who received conservative management. Among the 37 patients, 25 underwent surgery with curative intent. Results: The two-year overall survival rate among surgically treated patients was 77%, with local recurrence-free survival and metastasis-free survival rates of 77% and 57%, respectively. Postoperative complications occurred in approximately one-third of the cases. Compared to those without complications, patients with complications were older (p = 0.025), had poorer performance status (p = 0.017), were likely to have trunk involvement (p = 0.01), and had larger tumor sizes (p = 0.025). No significant prognostic factors for overall survival were identified. Conclusions: While surgery is not without risk, our results can provide useful information for both physicians and patients to discuss and explain possible outcomes with surgical treatment.

DOI： 10.3390/cancers17121940

Chen, AP; Coyne, GHO; Wolters, P; Martin, S; Farschtschi, S; Blanco, I; Chen, ZP; Darrigo, LG Jr; Eoli, M; Whittle, JR; Nishida, Y; Lamarca, R; de la Rosa, R; Adeyemi, A; Herrero, I; Llorente, N; Diede, SJ; Dombi, E; Wolkenstein, P

JOURNAL OF CLINICAL ONCOLOGY Vol. 43 ( 16_SUPPL ) 2025.6

Methotrexate, Doxorubicin, and Cisplatin Versus Methotrexate, Doxorubicin, and Cisplatin plus Ifosfamide in Poor Responders to Preoperative Chemotherapy for Newly Diagnosed High-Grade Osteosarcoma (JCOG0905): A Multicenter, Open-Label, Randomized Trial Reviewed Open Access

Hiraga, H; Machida, R; Kawai, A; Kunisada, T; Yonemoto, T; Endo, M; Nishida, Y; Nagano, A; Ae, K; Yoshida, S; Asanuma, K; Toguchida, J; Furuta, T; Nakayama, R; Akisue, T; Hiruma, T; Morii, T; Nishimura, H; Hiraoka, K; Takeyama, M; Emori, M; Tsukushi, S; Hatano, H; Kawashima, H; Isu, K; Tanaka, K; Kataoka, T; Fukuda, H; Iwamoto, Y; Ozaki, T

JOURNAL OF CLINICAL ONCOLOGY Vol. 43 ( 16 ) page： 1886 - 1897 2025.6

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

PURPOSEOur previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] - six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp.METHODSJCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of.1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126).RESULTSOf the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively.CONCLUSIONEvidence from JCOG0905 does not support the addition of IF for patients with PrRsp.

DOI： 10.1200/JCO-24-01281

Comparative surgical invasiveness of internal fixation for pathological fractures in metastatic bone disease versus traumatic fractures: a quantitative analysis of operative time and blood loss Reviewed Open Access

Hayashi, K; Takenaka, S; Ohshika, S; Kawashima, H; Endo, M; Kobayashi, E; Nakata, E; Nakamura, T; Horiuchi, K; Hamada, T; Nishida, Y; Morii, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 55 ( 6 ) page： 615 - 620 2025.6

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

Objective The primary aim of this study was to compare the surgical invasiveness of internal fixation for pathological fractures caused by metastatic bone tumors with that for traumatic fractures. The secondary aim was to identify factors contributing to the complexity of surgeries for metastatic bone disease and provide insights for improving surgical strategies by analyzing operative time and blood loss. Methods Patients undergoing internal fixation for femoral fractures at 10 institutions between January 2021 and December 2023 were included. Traumatic and metastatic pathological fractures were analyzed, excluding patients aged <18 years and those with benign or atypical fractures. Factors influencing blood loss and operative time were assessed using univariate regression and multivariate modeling (P < 0.05). Results A total of 275 patients (male = 97, female = 178) with a mean age of 76 years were included. Patients had 230 traumatic and 45 metastatic fractures, with proximal fractures being the most common (n = 225). Intramedullary nailing was the predominant fixation method (n = 231). Blood loss and operative times were significantly affected by the fracture cause, site, and reduction procedures (P < 0.05). Metastatic, distal, or diaphyseal fractures and reduction procedures resulted in higher blood loss and longer operative times. Multivariate analysis confirmed these factors as significant predictors. Conclusions Surgeries for metastatic fractures are more invasive than those for traumatic fractures because of compromised bone integrity and procedural complexity. Operative time is a key indicator of surgical invasiveness, highlighting the need for tailored surgical approaches to manage metastatic bone disease effectively.

DOI： 10.1093/jjco/hyaf039

Predictive variables for intraoperative blood loss and surgical time in resection of malignant soft tissue tumors without reconstruction Reviewed

Nakamura, T; Kobayashi, E; Takenaka, S; Endo, M; Hayashi, K; Nakata, E; Ohshika, S; Kawashima, H; Hamada, T; Horiuchi, K; Nishida, Y; Hasegawa, M; Morii, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 55 ( 6 ) page： 610 - 614 2025.6

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

Background Procedural techniques such as dissection and separation of blood vessels or nerves from the tumor for preserving limbs and functions involves high surgical difficulty. We hypothesized the relation of vessel and/or nerve preservation to surgical time and blood loss, accurately reflecting surgical difficulty. In this study, we elucidated the variables affecting surgical time and intraoperative bleeding in patients with malignant soft tissue tumors who did not undergo any reconstruction after tumor resection. Methods We included 153 patients with malignant oft tissue tumors in the trunk (n = 72), thigh (n = 68), and upper arm (n = 13) at nine institutions. We analyzed the possible predictive variables affecting surgical time and intraoperative bleeding. Results Overall, the study included 153 patients (85 men and 68 women) with a mean age of 65 years. The tumors were primary soft tissue sarcoma (STS) (n = 114), local recurrent STS (n = 25), and soft tissue metastasis (n = 14). The median number of participating surgeons was three. The mean and median surgical time were 144.6 and 123 min, respectively. The mean and median intraoperative bleeding were 157.1 and 55 mL, respectively. Tumor size, depth, dissection and separation of blood vessels from the tumor, dissection and separation of nerve from the tumor, and the number of participating surgeons were significantly related to the surgical time and intraoperative bleeding. Conclusions The procedure of dissection and separation of blood vessels and nerves from the tumor were related to surgical time and intraoperative bleeding in patients with malignant soft tissue tumors, especially large and deep tumors.

DOI： 10.1093/jjco/hyaf030

希少疾患患者へのリハビリテーション診療は必須である

Clinical factors associated with valgus knee deformities in patients with multiple osteochondromas Reviewed Open Access

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

MEDICINE Vol. 104 ( 19 ) page： e42359 2025.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Medicine United States

Multiple osteochondromas (MO) occur in approximately 1 in 50,000 people/yr. One in 3 patients with MO will develop valgus knee deformity (VKD), but the predictive factors for VKD are unclear. The purpose of this study was to examine the factors associated with VKD in patients with MO. From January 2003 to December 2018, 64 patients with MO visited the Nagoya University Hospital for the 1st time. Thirty-three patients with 66 limbs were sequentially included in the study after excluding 12 patients with a history of lower extremity surgery, 15 patients whose knee X-rays were unavailable, and 4 patients whose age at the last examination was <7 years. Limbs with femorotibial angle (FTA)≥175° were defined as the normal group (Group N) and limbs with FTA<175° as the valgus group (Group V), and clinical factors collected retrospectively from the medical records were compared between the 2 groups. The initial and final X-rays were compared in a subgroup analysis of 8 patients whose initial examination was <10 years old and who were followed for more than 5 years. Twenty-four males and 9 females with a median age of 17 years at the last X-rays were included in the study. The mean follow-up period was 43±53 months, and the median FTA was 174.5°. Group N consisted of 32 limbs and Group V consisted of 34 limbs. Multivariate analysis was performed using the 5 factors with P-values <.15 in the univariate analysis of comparison between the 2 groups, and only medial proximal tibial angle showed significant differences (P<.001). In the subgroup analysis, multivariate analysis showed that the femoral neck-shaft angle showed significant differences between the 2 groups at the initial evaluation (P<.001). Our study suggests that medial proximal tibial angle is associated with VKD in patients with MO. Small neck-shaft angle was significantly associated with VKD, even before it became obvious. In order to study how VKD is formed, imaging of the hip and ankle joints and X-rays of the entire lower extremity should be performed in more cases.

DOI： 10.1097/MD.0000000000042359

Prognostic impact of preoperative cachexia in patients undergoing major hepatopancreatobiliary surgery for malignancy Reviewed Open Access

Fugane, Y; Tanaka, S; Mizuno, Y; Nakajima, H; Yamamoto, H; Inoue, T; Nagaya, M; Nishida, Y; Onoe, S; Yamaguchi, J; Mizuno, T; Yokoyama, Y; Ebata, T

CLINICAL NUTRITION Vol. 47 page： 112 - 118 2025.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical Nutrition

Background & aims: Data regarding the association between cachexia and clinical outcomes in hepatopancreatobiliary (HPB) malignancies are limited. This retrospective study sought to investigate the prognostic significance of preoperative cachexia in patients undergoing major HPB surgery for malignancies. Methods: Data from patients, who underwent major open surgery for HPB malignancies between March 2014 and December 2018, were retrospectively reviewed. Cachexia was evaluated a few days before surgery, and defined according to modified Asian Working Group for Cachexia criteria: low body mass index (<21 kg/m2) and decreased handgrip strength (<28 kg [males] and <18 kg [females]) or elevated C-reactive protein level (>0.5 mg/dL). The primary endpoint was postoperative overall survival (OS); secondary endpoints included disease-free survival (DFS) and postoperative complications. Results: Of 332 patients (228 male; mean age, 68.8 ± 10.3 years), 93 (28 %) had preoperative cachexia. There were 154 (46 %) deaths and 181 (55 %) combined events (death or recurrence) during a five-year follow-up (mean, 3.3 ± 1.7 years), with no significant differences in major postoperative complications between the 2 groups (P = 0.329). After adjusting for covariates, cachexia (n = 93) exhibited significant associations with shorter OS (adjusted hazard ratio [HR] 1.65 [95 % confidence interval (CI) 1.18–2.30]; P = 0.004) and DFS (adjusted HR 1.39 [95 % CI 1.01–1.91; P = 0.043) compared with non-cachexia (n = 239). Cachexia significantly shortened OS only in a subset with pathological stage ≤ II disease (adjusted HR 2.45 [95 % CI 1.27–4.74]; P = 0.008) but not otherwise (P for interaction, 0.040). Conclusions: Preoperative cachexia did not affect short-term surgical complications but significantly deteriorated postoperative prognosis in patients who underwent surgery for HPB malignancies.

DOI： 10.1016/j.clnu.2025.02.014

Tocilizumab treatment for inflammatory dedifferentiated liposarcoma: pre- and posttreatment imaging and pathological changes Reviewed Open Access

Nishida, Y; Shimada, S

ESMO OPEN Vol. 10 ( 4 ) page： 104530 2025.4

Selumetinib for symptomatic, inoperable plexiform neurofibromas in pediatric patients with neurofibromatosis type 1: the first single-center real-world case series in Japan Reviewed Open Access

Nishida, Y; Nonobe, N; Kidokoro, H; Kato, T; Takeichi, T; Ikuta, K; Urakawa, H; Sakai, T; Koike, H; Fujito, T; Imagama, S

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 55 ( 4 ) page： 372 - 376 2025.4

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Clinical Oncology

Objective: In Japan, selumetinib is used in pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibroma (PN). However, there have been no real-world reports on Japanese patients. In this study, we reported a single-center, short-term experience with selumetinib after its approval in Japan. Methods: We prospectively collected data from 11 pediatric NF1 patients with symptomatic, inoperable PN who were initiated on selumetinib between November 2022 and May 2023; the selumetinib was administered by the same physician. Various patient factors, tumors, dose and efficacy of selumetinib, and adverse events (AE) were investigated. Results: Of 11 patients included, 7 were male, with a mean age of 14 years. The sites of symptomatic main PN included the head and neck, pelvis to lower extremities, and paraspinal lesions in five, three, and three patients, respectively. The median maximum diameter of the main PN was 91 mm, and the median follow-up duration was 19 months. All patients with pain or motor dysfunction experienced symptom improvement after treatment, and the tumors tended to shrink in 7 of the 11 patients (64%). Among the six patients with disfigurements, only one experienced improvement. Of 59 AEs observed, 58 (98%) were grades 1 and 2, and 5 patients (46%) underwent temporary selumetinib withdrawal due to AEs. One patient discontinued the drug (9%) because of rash dermatitis. Conclusions: Despite the relatively short-term results, no serious AEs were observed, and many patients benefited from selumetinib treatment. In some patients, administration was discontinued or interrupted because of the balance between benefits and AEs, and further data are needed to better understand the general safety and efficacy of selumetinib.

DOI： 10.1093/jjco/hyae184

Activated cardiac fibroblasts are a primary source of high-molecular-weight hyaluronan production Reviewed Open Access

Little, DT; Howard, CM; Pendergraft, E; Brittian, KR; Audam, TN; Lukudu, EW; Smith, J; Nguyen, D; Nishida, Y; Yamaguchi, Y; Brainard, RE; Singhal, RA; Jones, SP

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Vol. 328 ( 3 ) page： C939 - C953 2025.3

Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Physiology Cell Physiology

During acute myocardial infarction, the composition of the extracellular matrix changes remarkably. One of the most notable changes in the extracellular matrix is in the accumulation of collagen; however, hyaluronan rivals collagen in its abundance. Yet, the extent to which specific cells and enzymes may contribute to such accumulation has been largely unexplored. Here, we hypothesized that activated cardiac fibroblasts produce hyaluronan via hyaluronan synthase 2 (HAS2). We show that hyaluronan accumulates following myocardial infarction and persists through at least 4 wk. Our analyses of failing heart RNA sequencing data suggest that fibroblasts are the cells most changed in the expression of HAS2. Given these insights, we used HAS2 gain- and loss-of-function approaches to examine the extent to which activated cardiac fibroblasts produce hyaluronan. Transforming growth factor b (TGFb)-induced activation of fibroblasts caused a significant increase in Has2 mRNA and concomitant accumulation of hyaluronan >1 MDa in size. Deletion of Has2 abrogated TGFb-induced production of hyaluronan. In addition, overexpression of Has2 was sufficient to cause an increase in hyaluronan accumulation in the absence of TGFb-induced activation. Our data indicated negligible impacts of Has2 on proliferation, migration, and collagen production. Exposing fibroblasts to exogenous hyaluronan also had minimal impact on fibroblasts. We also assessed whether fibroblast-borne Hyal2 plays a role in the degradation of hyaluronan, and our data indicated little impact of Hyal2 on hyaluronan accumulation (or even any impacts on the transcriptional profile of fibroblasts). Activated fibroblasts produce high-molecular-weight hyaluronan via Has2, which occurs independent of other fibroblast functions.

DOI： 10.1152/ajpcell.00786.2024

Implant failure of the Compress prosthesis: a case report Reviewed Open Access

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

JOURNAL OF MEDICAL CASE REPORTS Vol. 19 ( 1 ) page： 6 2025.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Case Reports

Background: The Compress is designed to achieve bone formation and stability by applying pressure at the bone–implant interface, minimizing the likelihood of aseptic loosening, which is a complication of stem implants. Herein, we report two cases of implant failure using the Compress. Case presentation: Case 1 describes a 36 year-old Japanese man who underwent extraarticular tumor resection, Compress arthroplasty, and reconstruction with a gastrocnemius flap after preoperative chemotherapy for a secondary malignant giant cell tumor in the right distal femur. Postoperatively, partial weight-bearing was started at 6 weeks, and full weight-bearing was allowed at 10 weeks. One year after the surgery, a fall caused implant failure. No bone formation at the implant–bone interface was observed on radiographs immediately prior to the failure. Bone formation was achieved at the interface 1 year after revision arthroplasty, and the patient was able to walk unassisted with a brace. Case 2 describes a 14 year-old Japanese boy who underwent wide surgical resection of osteosarcoma in the left tibia, Compress arthroplasty, and reconstruction with a gastrocnemius flap after preoperative chemotherapy. The postoperative weight-bearing schedule was the same as that of case 1. One year after the surgery, the patient experienced implant failure. A revision arthroplasty was performed. One year after revision surgery, the patient was able to walk unassisted. Conclusion: Although the risk factors for Compress failure remain unknown, it is important to consider patient characteristics that may inhibit bone formation, implant selection, postoperative loading timing, and radiographs of bone formation at the implant interface when using the Compress.

DOI： 10.1186/s13256-024-05012-1

Japanese orthopaedic association (JOA) clinical practice guideline on the management of primary malignant bone tumors- Secondary publication Reviewed Open Access

Tsuchiya, K; Akisue, T; Ehara, S; Kawai, A; Kawano, H; Hiraga, H; Hosono, A; Hutani, H; Morii, T; Morioka, H; Nishida, Y; Oda, Y; Ogose, A; Shimose, S; Yamaguchi, T; Yamamoto, T; Yoshida, M

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 30 ( 1 ) page： 1 - 17 2025.1

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

Background: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. Methods: The guidelines were developed in accordance with “Minds Clinical Practice Guideline Development Handbook 2014″ and “Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. Results: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. Conclusion: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

DOI： 10.1016/j.jos.2023.11.007

西田佳弘

Vol. 61 ( 12 ) page： 1128 - 1128 2024.12

Clinical Features and Postoperative Mobilization following Total Aortic Arch Replacement Open Access

Tanaka Shinya, Hori Yuto, Yoshito Natsumi, Takagi Daichi, Nishida Yoshihiro, Mutsuga Masato, Kobayashi Kiyonori, Shirai Yuya, Tokuda Yoshiyuki, Tsuchikawa Yohei

International Heart Journal Vol. 65 ( 6 ) page： 1075 - 1078 2024.11

Language：English Publishing type：Research paper (scientific journal) Publisher：International Heart Journal Association

Open thoracic aortic surgery is believed to necessitate more intensive rehabilitation. This study aimed to compare the progress of postoperative rehabilitation between standard and delayed mobilization. A retrospective review was conducted on 199 patients who underwent isolated total aortic arch replacement via median sternotomy. Cases of in-hospital mortality and postoperative stroke were excluded. Based on the current guidelines for cardiovascular rehabilitation of the Japanese Circulation Society, patients were categorized into standard mobilization (could sit on the edge of bed within 2 days) and delayed mobilization (could not do so) groups. Rehabilitation progress was compared among both groups. Initial mobilization was delayed in 100 patients (delayed mobilization group), primarily because of respiratory failure (46.0%). Preoperative risk characteristics, including EuroSCORE II (median, 2.9 versus 3.5), were similar between the standard and delayed mobilization groups. The delayed mobilization group had longer operation (median, 6.1 versus 8.0 hours, P < 0.001) and cardiopulmonary bypass (median, 3.2 versus 4.1 hours, P < 0.001) times. Independent ambulation occurred earlier in the standard mobilization group (median, 6.0 versus 8.0 days, P < 0.001).In conclusion, early initiation of sitting on the edge of the bed within 2 days was associated with earlier independent ambulation during postoperative rehabilitation, which supports the current guidelines. Longer operation and cardiopulmonary bypass times were associated with delayed mobilization initiation, suggesting the need for more tailored approaches in such cases.

DOI： 10.1536/ihj.24-261

尾﨑敏文, 大高洋平, 酒井良忠, 西村行秀, 西田佳弘, 藤原俊之, 宮本健史

Vol. 61 ( 11 ) page： 1120 - 1122 2024.11

JARM NEWS【Topics】新理事のご挨拶 Reviewed

酒井良忠, 西田佳弘, 尾﨑敏文, 西村行秀, 藤原俊之, 宮本健史, 大高洋平

リハビリテーション医学 Vol. 61 ( 11 ) page： 1120 - 1122 2024.11

Efficacy and Safety of Auranofin for Progressive Desmoid-Type Fibromatosis: The Study Protocol of an Open-Label Phase II Trial. Reviewed Open Access

Nishida Y, Ito K, Sakai T, Kinoshita F, Kuwatsuka Y, Kinoshita S, Imagama S

Cureus Vol. 16 ( 10 ) page： e71033 2024.10

Financial burden of surgical treatment for retroperitoneal sarcoma Reviewed

Yokoyama, Y; Sunagawa, M; Kurimoto, K; Sakai, T; Nishida, Y; Ebata, T; Kodera, Y

SURGERY TODAY Vol. 54 ( 10 ) page： 1201 - 1207 2024.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Surgery Today

Purposes: The purpose of this study was to compare the financial burden of surgery for retroperitoneal sarcoma (RPS) and gastric cancer (GC). Methods: All patients who underwent surgery for GC or RPS between 2020 and 2021 at Nagoya University Hospital were included. The clinical characteristics, surgical fees per surgeon, and surgical fees per hour were compared between the two groups. Results: The GC and RPS groups included 35 and 63 patients, respectively. In the latter group, 37 patients (59%) underwent tumor resection combined with organ resection; the most common organ was the intestine (n = 23, 37%), followed by the kidney (n = 16, 25%). The mean operative time (248 vs. 417 min, p < 0.001) and intraoperative blood loss (423 vs. 1123 ml, p < 0.001) were significantly greater in the RPS group than in the GC group. The mean surgical fee per surgeon was USD 1667 in the GC group and USD 1022 in the RPS group (p < 0.001) and USD 1388 and USD 777 per hour, respectively (p < 0.001). Conclusions: The financial burden of surgical treatment for RPS is unexpectedly higher than that for GC.

DOI： 10.1007/s00595-024-02831-z

The impact of goal-directed prehabilitation therapy on functional capacity in patients undergoing hepatobiliary and pancreatic surgery: A randomized clinical trial Reviewed Open Access

Mizuno, Y; Yokoyama, Y; Nakajima, H; Inoue, T; Tanaka, S; Nagaya, M; Inokawa, Y; Ando, M; Nishida, Y; Ebata, T

SURGERY Vol. 176 ( 2 ) page： 252 - 258 2024.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Surgery United States

Background: Emerging evidence has supported the idea that goal-directed prehabilitation is a promising approach to boost functional capacity in preoperative patients. However, its usefulness has not been tested in the hepatobiliary and pancreatic fields. The objective of this trial was to investigate the efficacy of goal-directed prehabilitation for improving functional capacity in patients who were planned to undergo major hepatobiliary and pancreatic operations. Methods: This assessor-blinded, parallel-arm, randomized clinical trial recruited patients who were scheduled for major hepatobiliary and pancreatic surgeries for malignancy. Patients were randomly allocated into the step goal-directed prehabilitation group as the test group and into the conventional prehabilitation group as the control group. Patients in the goal-directed prehabilitation group participated in a walking prehabilitation program with an intergrading goal of the step count. Patients in the conventional prehabilitation group received standard physical and nutritional prehabilitation. The primary outcome was change in the 6-minute walking distance, which ranged from the time before starting prehabilitation (baseline) to the time after completing prehabilitation (immediately before surgery). Results: Among 180 randomized patients, 144 patients were included in the primary analysis (73 patients in the conventional prehabilitation group and 71 patients in the goal-directed prehabilitation group). The mean change in the 6-minute walking distance was 27 meters in the conventional prehabilitation group and 31 meters in the goal-directed prehabilitation group (P = .633). Conclusion: In patients undergoing major hepatobiliary and pancreatic surgeries for malignancies, a goal-directed prehabilitation program did not result in a significantly greater increase in functional capacity than did conventional prehabilitation. Registration number: UMIN000038791 (https://www.umin.ac.jp/).

DOI： 10.1016/j.surg.2024.04.024

Final results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306. Reviewed

Preoperative Sarcopenia Severity and Clinical Outcomes after Total Hip Arthroplasty Reviewed Open Access

Tanaka, S; Kayamoto, A; Terai, C; Nojiri, S; Fugane, Y; Mori, T; Nagaya, M; Kako, M; Iida, H; Osawa, Y; Takegami, Y; Nishida, Y

NUTRIENTS Vol. 16 ( 13 ) 2024.7

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

The outcome of total hip arthroplasty (THA) in patients with end-stage arthritis of the hip is associated with preoperative physical status. This study was performed to examine the relationship between the preoperative severity of sarcopenia and clinical outcomes after THA. This retrospective cohort study was performed among 306 consecutive patients (mean age: 63.7 ± 12.9 years, 222 women) undergoing THA at a university hospital. The severity of sarcopenia was determined based on the skeletal muscle mass index (SMI), handgrip strength, and gait speed according to the criteria of the Asian Working Group for Sarcopenia 2019. The severe sarcopenia prevalence rate was 10.6%. Severe sarcopenia was significantly associated with the risk of delayed functional recovery (adjusted odds ratio, 2.82; 95% confidence interval, 1.03–7.72; p = 0.043) compared with the non-sarcopenia group after adjusting for pre-existing risk factors, including preoperative hip function and physical activity. The addition of SMI, handgrip strength, and gait speed to the model for risk of functional recovery delay significantly increased the area under the receiver operating characteristic curve (p = 0.038). Severe sarcopenia was significantly associated with poorer hip function and patient-reported outcomes at 6 months after surgery compared with the non-sarcopenia group. Severe sarcopenia was adversely associated with postoperative clinical outcomes in patients undergoing THA.

DOI： 10.3390/nu16132085

Tanaka, K; Machida, R; Endo, M; Kawai, A; Nakayama, R; Tsukushi, S; Asanuma, K; Hiraga, H; Hiraoka, K; Yoshida, S; Yonemoto, T; Imanishi, J; Katagiri, H; Nishida, Y; Nagano, A; Sekino, Y; Fukuda, H; Ozaki, T; Iwamoto, Y

JOURNAL OF CLINICAL ONCOLOGY Vol. 42 ( 16 ) 2024.6

Hand Grip Strength Assessment Based on Sarcopenia Diagnostic Criteria Predicts Swallowing Function Reviewed

Okada, T; Yamaguchi, H; Tanaka, S; Koyama, K; Hishida, A; Konno, S; Nakamura, M; Sugiura, H; Nishida, Y

DYSPHAGIA Vol. 39 ( 2 ) page： 223 - 230 2024.4

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

The purpose of this study is to clarify whether swallowing function can be inferred from grip strength. Based on the diagnostic criteria of sarcopenia, patients were divided into two groups according to grip strength, and it was analyzed whether there was a difference in the evaluation index for swallowing function between the two groups. Among the cases requesting evaluation of swallowing function from June 10, 2020 to October 28, 2020, 83 cases (mean age: 71.7 years, 59 males and 24 females) who received assessment tests and swallowing endoscopy were included. According to the diagnostic criteria for grip strength in the Asian working group in Sarcopenia, less than 28 kgf and 18 kgf were defined as the weak group for men and women, respectively. Hyodo scores, repeated salivary swallowing tests (RSST), maximum vocalization time (MPT), and dysphagia severity classification (DSS) were compared between the two groups. Of the 83 patients, 29 and 54 were in the normal group and weak group, respectively. In all indicators, the normal group showed significantly better results than the weak group: Hyodo score (2.4 vs. 4.0, p < 0.01), RSST (4.1 times vs. 2.4 times, p < 0.01), MPT (12.1 s vs. 5.9 s, p < 0.001), DSS (4.5 vs. 5.9, p < 0.001), respectively. In multiple regression analysis with DSS as the dependent variable, grip strength was a significant independent variable of DSS even after adjusting for age, gender, and body mass index. Grip strength assessment based on sarcopenia criteria can be a useful tool for estimating swallowing function.

DOI： 10.1007/s00455-023-10604-y

Clinical Outcomes of a Novel Unidirectional Porous β-Tricalcium Phosphate Filling in Distal Radius Fracture with Volar Locking Plate Fixation: Secondary Publication of the Japanese Version Reviewed Open Access

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study Reviewed Open Access

Tsuchikawa, Y; Tanaka, S; Kasugai, D; Nakagawa, R; Shimizu, M; Inoue, T; Nagaya, M; Nasu, T; Omote, N; Higashi, M; Yamamoto, T; Jingushi, N; Numaguchi, A; Nishida, Y

SCIENTIFIC REPORTS Vol. 14 ( 1 ) page： 5254 2024.3

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

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case–control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

DOI： 10.1038/s41598-024-55969-8

Whole genome and transcriptome analysis of bone and soft tissue sarcomas Reviewed

Hirai, T; Katayama, K; Shiraishi, Y; Kawai, A; Yoshida, A; Kobayashi, H; Ohtsu, T; Kunisada, T; Nishida, Y; Yoshida, S; Kondo, T; Shibata, T; Imoto, S; Matsuda, K; Hirata, M

CANCER SCIENCE Vol. 115 page： 384 - 384 2024.3

TGF-β signaling promotes desmoid tumor formation via CSRP2 upregulation Reviewed Open Access

Li, Y; Fujishita, T; Mishiro-Sato, E; Kojima, Y; Niu, YQ; Taketo, MM; Urano, Y; Sakai, T; Enomoto, A; Nishida, Y; Aoki, M

CANCER SCIENCE Vol. 115 ( 2 ) page： 401 - 411 2024.2

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

Desmoid tumors (DTs), also called desmoid-type fibromatoses, are locally aggressive tumors of mesenchymal origin. In the present study, we developed a novel mouse model of DTs by inducing a local mutation in the Ctnnb1 gene, encoding β-catenin in PDGFRA-positive stromal cells, by subcutaneous injection of 4-hydroxy-tamoxifen. Tumors in this model resembled histologically clinical samples from DT patients and showed strong phosphorylation of nuclear SMAD2. Knockout of SMAD4 in the model significantly suppressed tumor growth. Proteomic analysis revealed that SMAD4 knockout reduced the level of Cysteine-and-Glycine-Rich Protein 2 (CSRP2) in DTs, and treatment of DT-derived cells with a TGF-β receptor inhibitor reduced CSRP2 RNA levels. Knockdown of CSRP2 in DT cells significantly suppressed their proliferation. These results indicate that the TGF-β/CSRP2 axis is a potential therapeutic target for DTs downstream of TGF-β signaling.

DOI： 10.1111/cas.16037

The relationship between preoperative foot alignment and postoperative outcomes in patients who underwent initial total knee arthroplasty Reviewed Open Access

Hishida, A; Hiraiwa, H; Kadono, I; Yamaguchi, H; Okada, T; Terai, C; Kayamoto, A; Nishida, Y

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 86 ( 1 ) page： 91 - 103 2024.2

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

We compared the relationship between foot alignments and quality of life in patients who underwent initial total knee arthroplasty (TKA). Among the patients with knee osteoarthritis (KOA) who underwent TKA from May 2015 to May 2017 at our hospital, we focused on those in whom weight-bearing foot radiographs had been evaluated preoperatively. The hallux valgus angle and Meary angle were measured by preoperative radiography, and those with hallux valgus angles of 20 degrees or more were classified into the hallux valgus (HV) group, and those with Meary angles of 4 degrees or more into the high arch (HA) group. Also knee and ankle range of motion, knee pain Visual Analog Scale, and the 36-item short-form health survey (SF-36) were measured preoperatively and at discharge, and the amount of these changes was compared in the presence/absence of HV and HA. Regarding HV, there were no significant differences in any of these items between the HV and non-HV groups. However, the SF-physical function was significantly lower in the HA group than in the normal group. In addition, ankle dorsiflexion was lower in the HA group than that in the normal group, although this difference was not statistically significant. There was little improvement of the ankle dorsiflexion, and it was associated with deterioration of the physical function items of SF-36. In total knee arthroplasty patients with HA, physical therapy of the ankles and feet, as well as of the knees, was considered to enhance the improvement of physical function.

DOI： 10.18999/nagjms.86.1.91

Sudo, Y; Nishida, Y; Nakashima, H; Arai, T; Takatsu, T

MEDICINA-LITHUANIA Vol. 60 ( 1 ) 2024.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Medicina Lithuania

Postoperative loss of correction is a concern in cases of distal radius fracture with bone loss after surgery. The purpose of this study was to evaluate the usefulness of a β-tricalcium phosphate (β-TCP) with unidirectional pore structure (Affinos®: Kuraray Co., Ltd, Tokyo, Japan) with internal fixation in patients with bone defects during the correction of distal radius fractures. Thirty-nine patients (40 radii) treated between 2016 and August 2020 were included in the study. There were 8 males and 31 females; the mean age was 70.9 (32–88). The mean postoperative observation period was 14.6 (3.4–24) months. The bone defect that occurred in the surgery was filled with Affinos® and fixed with a locking plate. Radial inclination (RI), volar tilt (VT), and ulnar variance (UV) were evaluated after the operation and at the final observation. The start of absorption and the completion of replacement to the host bone of Affinos® were also evaluated. There were no complications associated with grafts of Affinos®. The mean time of translucent findings around artificial bone was 1.85 (0.5–6) months, and that of complete resorption was 10.6 (1.5–16.5) months after surgery. The mean RI was 21.82° after surgery and 21.16° at final observation. The mean VT was 8.54° after surgery and 8.50° at final observation. The mean UV was −0.3 mm after surgery and 0.5 mm at final observation. Affinos® was resorbed relatively early, and host bone formation was observed. Filling of unidirectional pore structure β-TCP with internal fixation showed favorable outcomes in the surgery of distal radius fractures with bone defects.

DOI： 10.3390/medicina60010001

Potential drug interactions between pazopanib and proton pump inhibitors/potassium-competitive acid blockers in patients with soft tissue sarcoma Reviewed Open Access

Liang, Y; Maeda, O; Shimokata, T; Yokota, K; Koike, H; Sakai, T; Ikuta, K; Urakawa, H; Nishida, Y; Akiyama, M; Ando, Y

INTERNATIONAL CANCER CONFERENCE JOURNAL Vol. 13 ( 1 ) page： 63 - 67 2024.1

TWO CASES OF OSTEOSARCOMA WITH FAVORABLE LONG-TERM DISEASE CONTROL WITH GEMCITABINE AND DOCETAXEL COMBINATION THERAPY Reviewed

Ichikawa, D; Kikui, H; Sekimizu, M; Hattori, H; Koike, H; Ikuta, K; Nishida, Y; Horibe, K; Maeda, N

PEDIATRIC BLOOD & CANCER Vol. 71 page： S35 - S36 2024.1

これからの生物学的再建　骨・軟部腫瘍手術における遊離血管柄付き骨移植による再建 Reviewed

生田国大, 酒井智久, 小池宏, 藤戸健雄, 西田佳弘

日本整形外科学会雑誌 Vol. 98巻 page： 805 - 809 2024

膝関節周囲軟部肉腫術後の膝関節機能の検討 Reviewed

小池宏, 生田国大, 西田佳弘

日本整形外科学会雑誌 Vol. 98 2024

後頸部軟部腫瘍の1例 Reviewed

小池宏, 酒井智久, 西田佳弘, 生田国大

東海骨軟部腫瘍 Vol. 30巻 page： 17 - 18 2024

左大腿軟部腫瘍の1例 Reviewed

酒井智久, 生田国大, 小池宏, 伊藤鑑, 西田佳弘

東海骨軟部腫瘍 Vol. 30 page： 43 - 44 2024

右大腿骨遠位骨腫瘍の1例 Reviewed

小池宏, 生田国大, 酒井智久, 伊藤鑑, 西田佳弘

東海骨軟部腫瘍 Vol. 30 page： 27 - 28 2024

右下腿軟部腫瘍の1例 Reviewed

小池宏, 生田国大, 酒井智久, 西田佳弘

東海骨軟部腫瘍 Vol. 30巻 page： 11 - 12 2024

A Case of Intractable Complex Regional Pain Syndrome Successfully Treated with a Combination of Regional Anesthesia and Physical Therapy

Ando Takahiro, Nishiwaki Kimitoshi, Yamaguchi Hidetoshi, Nishida Yoshihiro, Hishida Aika

The Japanese Journal of Rehabilitation Medicine Vol. 60 ( 12 ) page： 1105 - 1110 2023.12

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Association of Rehabilitation Medicine

We report a case of intractable complex regional pain syndrome (CRPS). The pain improved with regional anesthesia and physical therapy.A 24-year-old man with hemophilia A, developed throbbing pain from his left foot to the ankle, with no identifiable cause. No organic abnormalities were observed. He diagnosed with CRPS at the pain clinic and admitted to the hospital 10 months after symptom onset for physical therapy with regional anesthesia under clotting factor replacement therapy. Spinal anesthesia was administered on the first and second day of hospitalization, and plantar load stimulation and ankle stretching were performed in the operating room. Subsequently, sciatic nerve blocks and continuous epidural blocks were given, and plantar contact training, ankle joint ROM training, and parallel bar walking training were conducted with cognitive behavioral therapy. Sciatic nerve blocks were continued after discharge. Ninety-five days after onset, the patient was re-admitted for physical therapy, and ROM exercises, partial weight bearing, and gait training together with sciatic nerve blocks and cognitive-behavioral therapy. On discharge following re-admission, the pain improved. The patient walked using one crutch. One year later, the pain further improved, and the patient walked independently.The combination of regional anesthesia, physical therapy, and cognitive behavioral therapy created a virtuous cycle of pain relief, improved physical functions, and prevented withdrawal from catastrophizing, ultimately leading to overall improvement.

DOI： 10.2490/jjrmc.23008

Clinical Outcome in Patients With High-grade Soft-tissue Sarcoma Receiving Prosthetic Replacement After Tumor Resection of the Lower Extremities: Tokai Musculoskeletal Oncology Consortium Study Reviewed Open Access

In-Hospital Fall Risk Prediction by Objective Measurement of Lower Extremity Function in a High-Risk Population Reviewed Open Access

Tanaka, S; Imaizumi, T; Morohashi, A; Sato, K; Shibata, A; Fukuta, A; Nakagawa, R; Nagaya, M; Nishida, Y; Hara, K; Katsuno, M; Suzuki, Y; Nagao, Y

JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION Vol. 24 ( 12 ) page： 1861 - 1867.e2 2023.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of the American Medical Directors Association

Objectives: Limited data exist regarding association between physical performance and in-hospital falls. This study was performed to investigate the association between physical performance and in-hospital falls in a high-risk population. Design: Retrospective cohort study. Setting and Participants: The study population consisted of 1200 consecutive patients with a median age of 74 years (50.8% men) admitted to a ward with high incidence rates of falls, primarily in the departments of geriatrics and neurology, in a university hospital between January 2019 and December 2021. Methods: Short Physical Performance Battery (SPPB) was measured after treatment in the acute phase. As the primary end point of the study, the incidence of in-hospital falls was examined prospectively based on data from mandatory standardized incident report forms and electronic patient records. Results: SPPB assessment was performed at a median of 3 days after admission, and the study population had a median SPPB score of 3 points. Falls occurred in 101 patients (8.4%) over a median hospital stay of 15 days. SPPB score showed a significant inverse association with the incidence of in-hospital falls after adjusting for possible confounders (adjusted odds ratio for each 1-point decrease in SPPB: 1.19, 95% CI 1.10-1.28; P < .001), and an SPPB score ≤6 was significantly associated with increased risk of in-hospital falls. Inclusion of SPPB with previously identified risk factors significantly increased the area under the curve for in-hospital falls (0.683 vs. 0.740, P = .003). Conclusion and Implications: This study demonstrated an inverse association of SPPB score with risk of in-hospital falls in a high-risk population and showed that SPPB assessment is useful for accurate risk stratification in a hospital setting.

DOI： 10.1016/j.jamda.2023.07.020

Nakamura, T; Sakai, T; Tsukushi, S; Kimura, H; Wasa, J; Hosono, K; Izubuchi, Y; Kozawa, E; Nagano, A; Asanuma, K; Sudo, A; Nishida, Y

IN VIVO Vol. 37 ( 6 ) page： 2642 - 2647 2023.11

Language：English Publishing type：Research paper (scientific journal) Publisher：In Vivo

Aim: This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade soft tissue sarcoma (STS) who underwent prosthetic replacement reconstruction after lower extremity tumor resection. Patients and Methods: We retrospectively collected the data of 27 patients with high-grade STS. The mean follow-up duration after prosthetic replacement was 44.7 months. Results: The mean age at surgery was 63 years. The mean tumor size was 16 cm. For reconstruction, proximal femur replacement was performed in 15 patients, distal femur replacement in six, and total femur replacement in six. The major complications were infections in nine patients and aseptic loosening in four. Nine patients developed local recurrence. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one. The 5-year prosthetic survival rate was 51.1%. At the final follow-up, amputation was performed in five patients. The 5-year limb salvage rate was 76.8%. The mean functional score of the 25 patients who could be assessed was 16.0 (53%). Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. The 5-year overall survival rate in the remaining 22 patients was 45.3%. Conclusion: We identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is needed for surgical complications and oncological events after surgery.

DOI： 10.21873/invivo.13372

Phase I trial of NY-ESO-1 TCR-T cell therapy combined with nanoparticulate vaccine but without lymphodepletion for STS Reviewed Open Access

Ishihara, M; Nishida, Y; Kitano, S; Kawai, A; Harada, N; Miyahara, Y; Hattori, H; Takada, K; Emori, M; Kakunaga, S; Endo, M; Matsumoto, Y; Sasada, T; Sato, E; Yamada, T; Matsumine, A; Nagata, Y; Kageyama, S; Shiku, H

ANNALS OF ONCOLOGY Vol. 34 page： S1391 - S1391 2023.11

Clinical investigation for the mechanisms of anaphylactic symptoms in osteoarthritis patients after diclofenac etalhyaluronate administration Reviewed Open Access

Nishida, Y; Yagami, A; Takada, S; Muramatsu, D; Nobuoka, Y; Okayama, Y

MODERN RHEUMATOLOGY Vol. 34 ( 4 ) page： 820 - 830 2023.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Modern Rheumatology

Objective: This study was conducted to investigate the mechanisms of anaphylaxis in patients with osteoarthritis of the knee and hip after diclofenac etalhyaluronate [product name: JOYCLU® (JCL)] intra-articular injection and to determine the utility of tests to investigate the mechanism involved. Methods: In this observational study in Japan, patients aged ≥20 years with knee or hip osteoarthritis who received JCL intra-articular injection experienced anaphylactic symptoms considered related to JCL (‘experienced patients’) or did not experience allergic symptoms considered related to JCL (‘non-experienced patients’). Basophil activation tests (BATs), specific immunoglobulin E (IgE) antibody testing by enzyme-linked immunosorbent assays (ELISAs) or immunochromatographic kit, and genome-wide association studies (GWASs) were conducted using patient blood and saliva. Results: Thirteen experienced patients and 14 non-experienced patients were tested. Seven experienced patients tested positive by BAT using diclofenac etalhyaluronate-containing test substances. Diclofenac-specific IgE antibodies were detected in four of seven BAT-positive patients but not in the non-experienced patients. Specific IgE antibody testing by immunochromatographic kit and genome-wide association study showed no clear results. Conclusions: These findings suggest that anaphylaxis occurs after JCL administration via an IgE-mediated mechanism and that diclofenac etalhyaluronate may be involved in this mechanism. BAT and diclofenac-specific IgE enzyme-linked immunosorbent assay may be useful tests for investigating the mechanisms of anaphylactic reactions after JCL administration.

DOI： 10.1093/mr/road100

The current management of clear cell sarcoma Reviewed

Ikuta, K; Nishida, Y; Imagama, S; Tanaka, K; Ozaki, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 53 ( 10 ) page： 899 - 904 2023.10

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

Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma with a high propensity for lymphatic metastasis and poor prognosis. It is characterized by the translocation of t (12;22), resulting in the rearrangement of the EWSR1 gene and overexpression of MET. Despite improvements in the diagnosis and treatment of soft tissue sarcomas, the management of CCSs remains challenging owing to their rarity, unique biological behaviour and limited understanding of their molecular pathogenesis. The standard treatment for localized CCSs is surgical excision with negative margins. However, there is an ongoing debate regarding the role of adjuvant chemotherapy, radiotherapy and lymphadenectomy in the management of this disease. CCSs are usually resistant to conventional chemotherapy. Targeted therapies, such as sunitinib and MET inhibitors, may provide promising results. Immunotherapy, particularly immune checkpoint inhibitors, is currently under investigation as a potential treatment option for CCSs. Further research is needed to better understand the biology of CCSs and develop effective therapeutic strategies. The purpose of this review is to provide a comprehensive overview of current knowledge and advances in the diagnosis and treatment of CCSs.

DOI： 10.1093/jjco/hyad083

特集脊髄および末梢神経鞘腫瘍のすべて -神経鞘腫瘍の手術:末梢神経鞘腫瘍-悪性末梢神経鞘腫瘍 Reviewed

Efficacy of rehabilitation initiated in the early phase after simultaneous deceased donor liver and kidney transplantation: A case report Reviewed Open Access

Tanaka, S; Mizuno, Y; Nojiri, S; Futamura, D; Nagaya, M; Nishida, Y; Sano, Y; Ishida, S; Kato, M; Kurata, N; Jobara, K; Fujimoto, Y; Ogura, Y

MEDICINE Vol. 102 ( 38 ) page： e35324 2023.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Medicine United States

Rationale: The purpose of this case report is to describe a case of successful early rehabilitation intervention for simultaneous liver and kidney transplantation (SLKT). Patient concerns: A 51-year-old Japanese man was diagnosed with Caroli disease 27 years ago. Hemodialysis was introduced due to end-stage renal disease 17 years ago. Diagnoses: After successful SLKT, the patient was extubated on postoperative day (POD) 1, liberated from dialysis on POD 4, and discharged from the intensive care unit on POD 9. Interventions: Supervised rehabilitation was started on POD 2, and the patient was able to walk 100 m on POD 9. Electrical muscle stimulation therapy was started to improve muscle weakness in both legs on POD 16, and aerobic exercise using a cycle-ergometer was started on POD 24. Outcomes: The 6-minute walking distance improved from 324 m on POD 14 to 501 m on POD 28. The patient could walk 4000 to 5000 steps per day at hospital discharge, and was discharged home on POD 32. There were no adverse events, including worsening hepatic or renal function, during the rehabilitation period. One month after discharge, the patient was able to perform 30 to 40 minutes of aerobic exercise every day, and returned to work 5 months after discharge. Lessons: This case shows that early rehabilitation intervention immediately after SLKT safely and rapidly improved physical performance without adverse events. The results in the present case suggest that regular physical assessment and appropriate interventions with a variety of exercise modalities can contribute to improved physical performance in SLKT patients.

DOI： 10.1097/MD.0000000000035324

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study Reviewed Open Access

Yamamoto, H; Tanaka, S; Kasugai, D; Shimizu, M; Tsuchikawa, Y; Hori, Y; Fugane, Y; Inoue, T; Nagaya, M; Omote, N; Higashi, M; Yamamoto, T; Jingushi, N; Numaguchi, A; Goto, Y; Nishida, Y

SCIENTIFIC REPORTS Vol. 13 ( 1 ) page： 14529 2023.9

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

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

DOI： 10.1038/s41598-023-41684-3

Association between National Institutes of Health Stroke Scale and Functional Independence Measure scores in patients with ischemic stroke from convalescent rehabilitation outcomes Reviewed Open Access

Senda, J; Ito, K; Kotake, T; Mizuno, M; Kishimoto, H; Yasui, K; Nakagawa-Senda, H; Katsuno, M; Nishida, Y; Sobue, G

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 85 ( 3 ) page： 428 - 443 2023.8

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

We investigated the associations among neurological severity, activities of daily living (ADLs), and clinical factors in patients with ischemic stroke in convalescent rehabilitation outcome. The study sample included 723 patients with ischemic stroke (484 men and 239 women; mean age, 73.2 ± 8.5 years) for inpatient convalescent rehabilitation. National Institutes of Health Stroke Scale (NIHSS) was used to measure the neurological severity, and Functional Independence Measure (FIM) was used to assess ADLs at discharge. Leukoaraiosis was graded based on periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on magnetic resonance imaging. The correlations between NIHSS scores and total FIM scores were significant but relatively mild (r = –0.684, P < 0.001). Multiple regression analysis revealed that age and PVH grade significantly decreased their total FIM scores and affected the discrepancies between NIHSS scores at discharge (P < 0.001), but DWMH scores did not affect these results. Factors such as positive history of heart disease (P = 0.008) and bilateral infarction (P = 0.038) additionally decreased their total FIM scores and affected the discrepancies between NIHSS scores. These findings suggest that age, PVH, history of heart disease positive, and bilateral infarction in patients with ischemic stroke affected their performance of ADLs and the discrepancies between their neurological severities in convalescent rehabilitation outcomes, probably because the pathophysiological background of leukoaraiosis and these factors strongly decrease their ADL performance in post-phase ischemic stroke.

DOI： 10.18999/nagjms.85.3.428

Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo Reviewed Open Access

Zhang, JR; Nishida, Y; Koike, H; Zhuo, LS; Ito, K; Ikuta, K; Sakai, T; Imagama, S

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 24 ( 15 ) 2023.8

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

This study aimed to clarify the effects of ipriflavone, which effectively reduces KIAA1199 activity, on osteoarthritis (OA) development and progression in an in vivo OA mouse model. The OA model mice were divided into the ipriflavone (200 mg/kg/day) group and the control group. OA onset and progression were evaluated with the Mankin score, and KIAA1199 expression and hyaluronan (HA) accumulation were analyzed by immunostaining. The molecular weight of HA in the cartilage tissue and serum HA concentration were analyzed by chromatography and competitive HA enzyme-linked immunoassay. The effects of ipriflavone on the bovine cartilage explant culture under the influence of IL-1β were also investigated. In the ipriflavone group, Safranin-O stainability was well-preserved, resulting in significant reduction of the Mankin score (p = 0.027). KIAA1199 staining positivity decreased and HA stainability was preserved in the ipriflavone group. The serum HA concentration decreased, and the molecular weight of HA in the cartilage tissue increased in the ipriflavone group. The results of the cartilage explant culture indicated that ipriflavone could reduce GAG losses and increase the molecular weight of HA. Thus, ipriflavone may have an inhibitory effect on OA development/progression. Ipriflavone could be a therapeutic drug for OA by targeting KIAA1199 activity.

DOI： 10.3390/ijms241512422

西田佳弘, 浦川浩, 生田国大, 酒井智久, 小池宏, 藤戸健雄

脊椎脊髄ジャーナル Vol. 36 ( 5 ) page： 351 - 355 2023.6

A phase 1 trial of NY-ESO-1-specific TCR-engineered T-cell therapy combined with a lymph node-targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma Reviewed Open Access

Ishihara, M; Nishida, Y; Kitano, S; Kawai, A; Muraoka, D; Momose, F; Harada, N; Miyahara, Y; Seo, N; Hattori, H; Takada, K; Emori, M; Kakunaga, S; Endo, M; Matsumoto, Y; Sasada, T; Sato, E; Yamada, T; Matsumine, A; Nagata, Y; Watanabe, T; Kageyama, S; Shiku, H

INTERNATIONAL JOURNAL OF CANCER Vol. 152 ( 12 ) page： 2554 - 2566 2023.6

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

The efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T-cell receptor gene-modified T (TCR-T)-cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR-T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR-T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR-T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY-ESO-1)-specific TCR-T cells were infused twice into HLA-matched patients with NY-ESO-1+ soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR-T cells, and it was subcutaneously injected 1 day before and 7 days after the infusion of TCR-T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low-to-moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2 years by tumor imaging and long-term persistence of TCR-T cells in one patient. In conclusion, NY-ESO-1-specific TCR-T-cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY-ESO-1 epitope without lymphodepletion is feasible and can induce promising long-lasting therapeutic effects in refractory SS (Registration ID: JMA-IIA00346).

DOI： 10.1002/ijc.34453

A case of total knee arthroplasty (TKA) for lipoma arborescens of the knee Reviewed

TAKAHASHI Yu

The Central Japan Journal of Orthopaedic Surgery & Traumatology Vol. 66 ( 3 ) page： 475 - 476 2023.5

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer Reviewed Open Access

Nakajima, H; Yamaguchi, J; Takami, H; Hayashi, M; Kodera, Y; Nishida, Y; Watanabe, N; Onoe, S; Mizuno, T; Yokoyama, Y; Ebata, T

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY Vol. 28 ( 5 ) page： 688 - 697 2023.5

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

Background: Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. Study design: This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. Results: In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). Conclusion: Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.

DOI： 10.1007/s10147-023-02321-1

Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling Reviewed Open Access

Mori, N; Esaki, N; Shimoyama, Y; Shiraki, Y; Asai, N; Sakai, T; Nishida, Y; Takahashi, M; Enomoto, A; Mii, S

PATHOLOGY RESEARCH AND PRACTICE Vol. 245 page： 154443 2023.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Pathology Research and Practice

Osteosarcoma, the most common primary malignant bone tumor, is defined by the formation of neoplastic osteoid and/or bone. This sarcoma is a highly heterogeneous disease with a wide range of patient outcomes. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in various types of malignant tumors. We previously reported that CD109 is expressed in osteoblasts and osteoclasts in normal human tissues and plays a role in bone metabolism in vivo. While CD109 has been shown to promote various carcinomas through the downregulation of TGF-β signaling, the role and mechanism of CD109 in sarcomas remain largely unknown. In this study, we investigated the molecular function of CD109 in sarcomas using osteosarcoma cell lines and tissue. Semi-quantitative immunohistochemical analysis using human osteosarcoma tissue revealed a significantly worse prognosis in the CD109-high group compared with the CD109-low group. We found no association between CD109 expression and TGF-β signaling in osteosarcoma cells. However, enhancement of SMAD1/5/9 phosphorylation was observed in CD109 knockdown cells under bone morphogenetic protein-2 (BMP-2) stimulation. We also performed immunohistochemical analysis for phospho-SMAD1/5/9 using human osteosarcoma tissue and found a negative correlation between CD109 expression and SMAD1/5/9 phosphorylation. In vitro wound healing assay showed that osteosarcoma cell migration was significantly attenuated in CD109-knockdown cells compared with control cells in the presence of BMP. These results suggest that CD109 is a poor prognostic factor in osteosarcoma and affects tumor cell migration via BMP signaling.

DOI： 10.1016/j.prp.2023.154443

Investigation of inpatient convalescent rehabilitation outcomes in branch atheromatous disease Reviewed

Clinical results of active surveillance for extra-abdominal desmoid-type fibromatosis Reviewed Open Access

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

CANCER MEDICINE Vol. 12 ( 5 ) page： 5245 - 5254 2023.3

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

Background: The treatment of choice for desmoid-type fibromatosis (DF) has been changed to active surveillance (AS). However, few studies have reported clinical outcomes of AS modality in Asian countries. This study aimed to clarify the significance of AS as a DF treatment modality. Methods: A total of 168 lesions from 162 patients with extra-abdominal DF were included. The mean age at diagnosis was 39 years (1–88 years), and the median maximum tumor diameter at the first visit was 64.1 mm (13.2–255.8 mm). The clinical outcomes of AS and the risk factors requiring active treatment (AT) (defined as an event) from AS modality were investigated. Results: Of the 168 lesions, 94 (56%) were able to continue AS, with a 5-year event-free survival of 54.8%. Of the 68 lesions with PD, 21 (30.9%) lesions were able to continue AS. Neck location (p = 0.043) and CTNNB1 S45F mutation (p = 0.003) were significantly associated with the transition to AT, and S45F mutation was a significant factor associated with the transition to AT by multivariate analysis (hazard ratio: 1.96, p = 0.048). AT outcomes after AS were evaluable in 65 lesions, and 49 (75%) lesions did not require a transition to a second AT. Conclusions: AS was revealed as an effective treatment modality. The transition to AT needs to be considered for neck location and CTNNB1 S45F mutation DF. Good results can be obtained by selecting a treatment method that considers the tumor location even in cases that require intervention.

DOI： 10.1002/cam4.5329

Senda, J; Ito, K; Kotake, T; Mizuno, M; Kishimoto, H; Yasui, K; Katsuno, M; Nishida, Y; Sobue, G

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Vol. 32 ( 3 ) page： 106937 2023.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Stroke and Cerebrovascular Diseases

Purpose: We investigated inpatient convalescent rehabilitation outcomes of Branch atheromatous disease (BAD). Subjects and methods: The subjects were 116 patients with lenticulostriate artery territory - BAD (LSA-BAD) and 29 with paramedian pontine artery territory - BAD (PPA-BAD). For all patients, the National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM) scores, and Brunnstrom recovery stages (BRS) of the upper limb, fingers, and lower limb were measured on admission and at discharge. Results: There were no significant differences in clinical characteristics on admission between the LSA-BAD and PPA-BAD groups. The neurological severity of PPA-BAD, as measured by the NIHSS, was significantly milder compared with that of LSA-BAD upon admission (p = 0.015) and at discharge (p = 0.001). Patients with LSA-BAD had significantly less improvement in the BRS of the upper limb (p = 0.001), fingers (p < 0.001), and lower limb (p = 0.007) at discharge. Furthermore, they had significantly smaller changes in BRS between admission and discharge for the upper limb (p = 0.033) and fingers (p = 0.014) compared with patients with PPA-BAD. The improvement in BRS for patients with LSA-BAD tended to be limited to two stages; however, both patients with LSA-BAD and PPA-BAD saw sufficient gains in FIM at discharge. Conclusion: Rehabilitation outcomes following BAD in the convalescent period should be assessed in terms of improvements in pure-motor hemiparesis and activities of daily living. Furthermore, the disturbance patterns in the corticospinal tract by ischemic stroke lesions may be different between LSA-BAD and PPA-BAD.

DOI： 10.1016/j.jstrokecerebrovasdis.2022.106937

Which modality is better to diagnose high-grade transformation in retroperitoneal liposarcoma? Comparison of computed tomography, positron emission tomography, and magnetic resonance imaging Reviewed Open Access

Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA Reviewed Open Access

Cortes-Ciriano, I; Steele, CD; Piculell, K; Al-Ibraheemi, A; Eulo, V; Bui, MM; Chatzipli, A; Dickson, BC; Borcherding, DC; Feber, A; Galor, A; Hart, J; Jones, KB; Jordan, JT; Kim, RH; Lindsay, D; Miller, C; Nishida, Y; Proszek, PZ; Serrano, J; Sundby, T; Szymanski, JJ; Ullrich, NJ; Viskochil, D; Wang, X; Snuderl, M; Park, PJ; Flanagan, AM; Hirbe, AC; Pillay, N; Miller, DT

CANCER DISCOVERY Vol. 13 ( 3 ) page： 654 - 671 2023.3

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

Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling and chromosome 8 amplification, and show lower levels of immune cell infiltration. Retention of H3K27me3 leads to extensive genomic instability, but an immune cell-rich phenotype. Specific SCNAs detected in both tumor samples and cell-free DNA (cfDNA) act as a surrogate for H3K27me3 loss and immune infiltration, and predict prognosis.

DOI： 10.1158/2159-8290.CD-22-0786

Nakashima, Y; Yokoyama, Y; Ogawa, H; Sakakibara, A; Sunagawa, M; Nishida, Y; Mizuno, T; Yamaguchi, J; Onoe, S; Watanabe, N; Kawakatsu, S; Igami, T; Ebata, T

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY Vol. 28 ( 3 ) page： 482 - 490 2023.3

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

Background: Survival in patients with retroperitoneal liposarcoma (RPLS) depends on the surgical management of the dedifferentiated foci. The present study investigated the diagnostic yield of contrast-enhanced CT, 18F-fluorodeoxyglucose positron emission tomography (PET), and diffusion-weighted MRI in terms of dedifferentiated foci within the RPLS. Methods: Patients treated with primary or recurrent RPLS who underwent the above imaging between January 2010 and December 2021 were retrospectively reviewed. The diagnostic accuracy of the three modalities for histologic subtype of dedifferentiated liposarcoma (DDLS) and French Federation of Cancer Center (FNCLCC) grade 2/3 were compared using receiver operating characteristic curves and areas under the curves (AUCs). Results: The cohort involved 32 patients with 53 tumors; 30 of which exhibited DDLS and 31 of which did FNCLCC grades 2/3. The optimal thresholds for predicting DDLS were mean CT value of 31 Hounsfield Unit (HU) (AUC = 0.880, 95% CI 0.775–0.984; p < 0.001), maximum standardized uptake value (SUVmax) of 2.9 (AUC = 0.865 95% CI 0.792–0.980; p < 0.001), while MRI failed to differentiate DDLS. The cutoff values for distinguishing FNCLCC grades 1 and 2/3 were a mean CT value of 24 HU (AUC = 0.858, 95% CI 0.731–0.985; p < 0.001) and SUVmax of 2.9 (AUC = 0.885, 95% CI 0.792–0.978; p < 0.001). MRI had no sufficient power to separate these grades. Conclusions: Contrast-enhanced CT and PET were useful for predicting DDLS and FNCLCC grade 2/3, while MRI was inferior to these two modalities.

DOI： 10.1007/s10147-022-02287-6

An Effective Therapy that Antibody-Drug Conjugates Targeting Meflin (+) Cells for Osteosarcoma Reviewed

誌説 Competitionとcooperation Reviewed

西田佳弘

整形外科 Vol. 74 ( 2 ) page： 106 - 106 2023.2

Sakoda, T; Esaki, N; Ando, R; Miyai, Y; Iida, T; Matsuyama, M; Shiraki, Y; Mii, S; Nishida, Y; Takahashi, M; Enomoto, A

CANCER SCIENCE Vol. 114 page： 760 - 760 2023.2

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG) Reviewed

Morii, T; Anazawa, U; Sato, C; Iwata, S; Nakagawa, M; Endo, M; Nakamura, T; Ikuta, K; Nishida, Y; Nakayama, R; Udaka, T; Kawamoto, T; Kito, M; Sato, K; Imanishi, J; Akiyama, T; Kobayashi, H; Nagano, A; Outani, H; Toki, S; Nishisho, T; Sasa, K; Suehara, Y; Kawano, H; Ueda, T; Morioka, H

EJSO Vol. 49 ( 2 ) page： 353 - 361 2023.2

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

Background: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. Methods: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. Results: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. Conclusions: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

DOI： 10.1016/j.ejso.2022.08.024

Hyaluronan in articular cartilage: Analysis of hip osteoarthritis and osteonecrosis of femoral head Reviewed Open Access

Zhang, JR; Nishida, Y; Koike, H; Ito, K; Zhuo, LS; Nishida, K; Kimata, K; Ikuta, K; Sakai, T; Urakawa, H; Seki, T; Imagama, S

JOURNAL OF ORTHOPAEDIC RESEARCH Vol. 41 ( 2 ) page： 307 - 315 2023.2

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

Hyaluronan (HA) plays crucial roles in the maintenance of high-quality cartilage extracellular matrix. Several studies have reported the HA in synovial fluid in patients with osteoarthritis (OA), but few have described the changes of HA in articular cartilage of OA or idiopathic osteonecrosis of the femoral head (ONFH). KIAA1199 was recently reported to have strong hyaluronidase activity. The aim of this study was to clarify the HA metabolism in OA and ONFH, particularly the involvement of KIAA1199. Immunohistochemical analysis of KIAA1199 and HA deposition was performed for human OA (n = 10), ONFH (n = 10), and control cartilage (n = 7). The concentration and molecular weight (MW) of HA were determined by competitive HA ELISA and Chromatography, respectively. Regarding HA metabolism-related molecules, HAS1, HAS2, HAS3, HYAL1, HYAL2, and KIAA1199 gene expression was assessed by reverse transcriptase polymerase chain reaction. Histological analysis showed the overexpression of KIAA1199 in OA cartilage, which was accompanied by decreased hyaluronic acid binding protein (HABP) staining compared with ONFH and control. Little KIAA1199 expression was observed in cartilage at the collapsed area of ONFH, which was accompanied by a slight decrease in HABP staining. The messenger RNA (mRNA) expression of HAS2 and KIAA1199 was upregulated in OA cartilage, while the mRNA expression of genes related to HA catabolism in ONFH cartilage showed mostly a downward trend. The MW of HA in OA cartilage increased while that in ONFH cartilage decreased. HA metabolism in ONFH is suggested to be generally indolent, and is activated in OA including high expression of KIAA1199. Interestingly, MW of HA in OA cartilage was not reduced.

DOI： 10.1002/jor.25364

Fibrous dysplasia associated with secondary aneurysmal bone cyst in the left proximal femur Reviewed

TGF-β signaling promotes desmoid tumor formation in a mouse model Reviewed

Li, Y; Fujishita, T; Mishiro, E; Taketo, MM; Enomoto, A; Nishida, Y; Aoki, M

CANCER SCIENCE Vol. 114 page： 1833 - 1833 2023.2

Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients Open Access

Tsuchikawa Yohei, Tokuda Yoshiyuki, Ito Hideki, Shimizu Miho, Tanaka Shinya, Nishida Kazuki, Takeda Natsuki, Hori Masaya, Nishida Yoshihiro, Mutsuga Masato, Yamamoto Hiromasa, Takagi Daichi, Fukuta Akimasa

Circulation Journal Vol. 87 ( 2 ) page： 306 - 311 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Circulation Society

Background: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation.Conclusions: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

DOI： 10.1253/circj.cj-22-0416

Case report: Novel NIPBL-BEND2 fusion gene identified in osteoblastoma-like phosphaturic mesenchymal tumor of the fibula Reviewed Open Access

Sakai, T; Okuno, Y; Murakami, N; Shimoyama, Y; Imagama, S; Nishida, Y

FRONTIERS IN ONCOLOGY Vol. 12 page： 956472 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Oncology

Phosphaturic mesenchymal tumor (PMT) is a rare tumor that secretes fibroblast growth factor 23 (FGF23) and causes hypophosphatemia and tumor-induced osteomalacia (TIO). Fusion genes FN1-FGFR1 and FN1-FGF1 have been detected in some PMTs, but the pathogenesis of PMTs without these fusion genes remains unclear. Here, we report a 12-year-old boy with persistent muscle weakness and gait disturbance. Roentgenographic examination revealed a radiolucent lesion with endosteal scalloping in the left fibula, while his serum level of FGF23 was markedly increased. Combined with simple X-ray findings of other body parts, we suspected that TIO was caused by PMT, and resected the tumor. After resection, the serum level of FGF23 started to decrease immediately and normalized within 3 hours after resection, with this being earlier than normalization of the serum phosphorus level. In RNA sequencing, FN1-FGFR1 and FN1-FGF1 were not detected, but a novel NIPBL-BEND2 fusion gene was identified. When we forcedly expressed this fusion gene in HEK293T cells and MG63 cells, cell proliferation was enhanced in both cell lines. Furthermore, Gene set enrichment analysis of HEK293T cells showed significant upregulation of MYC-target genes. Our results suggest that this novel NIPBL-BEND2 fusion gene promotes cell proliferation possibly via the MYC pathway and might be one of the etiologies of PMTs other than FN1-FGFR1 or FN1-FGF1.

DOI： 10.3389/fonc.2022.956472

KATO Masataka

The Central Japan Journal of Orthopaedic Surgery & Traumatology Vol. 66 ( 1 ) page： 99 - 100 2023.1

Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study Reviewed Open Access

Suenobu, S; Terashima, K; Akiyama, M; Oguri, T; Watanabe, A; Sugeno, M; Higashimori, M; So, KR; Nishida, Y

NEURO-ONCOLOGY ADVANCES Vol. 5 ( 1 ) page： vdad054 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Neuro Oncology Advances

Background: Plexiform neurofibromas (PN) are a manifestation of neurofibromatosis type 1 (NF1) that may cause morbidity and impact health-related quality of life (HRQoL). Selumetinib (ARRY-142886, AZD6244) is an orally available, selective, mitogen-activated protein kinase kinase 1/2 inhibitor approved for children with NF1 and symptomatic, inoperable PN in regions including the USA (aged ≥2 years), EU (≥3 years), and Japan (≥3 years). This open-label, single-arm, phase I study evaluated selumetinib in Japanese children with NF1 and symptomatic, inoperable PN. Methods: Eligible patients (aged 3-18 years) received oral selumetinib (25 mg/m2 twice daily) continuously in 28-day cycles in a fasted state. Primary objectives were safety and tolerability. Secondary objectives included pharmacokinetics, efficacy, PN-related morbidities, and HRQoL. Results: Twelve patients (median age 13.3 years) were enrolled, received ≥1 selumetinib dose (data cutoff: cycle 13 day 1) with median follow-up of 11.5 months. All patients had baseline PN-related morbidities, most commonly disfigurement (91.7%) and pain (58.3%). Most frequently reported any-grade adverse events were dermatologic and gastrointestinal. Objective response rate was 33.3%; median duration of response was not reached. Most patients (83.3%) had target PN volume reduction versus baseline. No patients reported worsening of PN-related morbidities. Selumetinib was rapidly absorbed with moderate-to-high inter-patient variability in maximum plasma concentration and area under the concentration-time curve from time 0-6 hours. Conclusions: Consistent with results of the phase II SPRINT trial, 25 mg/m2 selumetinib twice daily was well tolerated with a manageable safety profile in Japanese children with NF1 and symptomatic, inoperable PN.

DOI： 10.1093/noajnl/vdad054

骨軟部　軟部腫瘍　良性軟部腫瘍・デスモイド型線維腫症の診断・治療指針 Reviewed

西田佳弘

最新主要文献とガイドラインでみる整形外科学レビュー 2023-’24 Vol. ー page： 255 - 260 2023

膝関節に発生した樹枝状脂肪腫に対して人工関節置換術を施工した1症例 Reviewed

西田佳弘

中部日本整形外科災害外科学会雑誌 Vol. 66 page： 475 - 476 2023

各種難病の最新治療情報　神経線維腫症1型の最新治療情報 Reviewed

西田佳弘

月刊難病と在宅ケア Vol. 29 page： 33 - 36 2023

【脊髄および末梢神経鞘腫瘍のすべて】神経症腫瘍の手術：末梢神経鞘腫瘍　悪性末梢神経鞘腫瘍 Reviewed

西田佳弘, 生田国大, 酒井智久, 小池宏, 藤戸健雄

脊椎脊髄ジャーナル Vol. 36 page： 351 - 355 2023

区域麻酔と理学療法の併用が奏功した難治性複合性局所疼痛症候群の1例 Reviewed

西田佳弘

The Japanese Journal of Rehabilitation Medicine Vol. 60 page： 1205 - 1210 2023

Surgical Treatment and Complications of Deep-Seated Nodular Plexiform Neurofibromas Associated with Neurofibromatosis Type 1 Reviewed Open Access

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

JOURNAL OF CLINICAL MEDICINE Vol. 11 ( 19 ) 2022.10

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

Background: Nodular plexiform neurofibromas in individuals with neurofibromatosis type 1 often cause significant symptoms and are treated with surgical excision despite the potential risk of complications. This study aimed to clarify the surgical outcomes of deep-seated nodular plexiform neurofibromas and identify the factors associated with postoperative complications. Methods: We retrospectively reviewed patients with neurofibromatosis type 1 who underwent surgical excision for deep-seated nodular plexiform neurofibromas in our hospital from 2015 to 2021. Enucleation while preserving the nerve fascicles was attempted first, and en bloc resection, ligating the nerve origin in cases in which the parent nerve was entrapped by the tumor, making the tumor difficult to dissect, was performed. Results: In 15 patients, 24 nodular plexiform neurofibromas received surgical excision. Sixteen tumors were enucleated, and eight were en bloc resected. The symptoms of all 10 patients with preoperative symptoms resolved after surgery. Four patients developed new neurological deficits immediately after surgery, two of whom had retained neurological symptoms at the last visit, but these symptoms were mild. Conclusions: The present study demonstrates that surgical treatment of nodular plexiform neurofibromas, even deep-seated neurofibromas, is safe with a low risk of severe complications and improvement in preoperative symptoms.

DOI： 10.3390/jcm11195695

A clinical trial of a unidirectional porous tricalcium phosphate filling for defects after resection of benign bone lesions: a prospective multicenter study Reviewed Open Access

Ikuta, K; Nishida, Y; Ota, T; Tsukushi, S; Kozawa, E; Nakashima, H; Yamada, K; Yamashita, S; Imagama, S

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 16060 2022.9

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

Affinos (Kuraray, Japan) is a β-tricalcium phosphate bone substitute with a unidirectional porous structure. This study aimed to investigate its efficacy on the healing process after filling for bone defects. Fifty-six patients who met the inclusion criteria were divided into cohort 1 (n = 30), including bones other than phalanges and metacarpal/tarsal bones, and cohort 2 (n = 26), including phalanges and metacarpal/tarsal bones. Semi-quantified scores for material resorption and trabeculation through the defect were evaluated with radiographs after surgery. In some patients, levels of bone metabolic markers were assessed. The values of resorption and trabeculation increased steadily with time, and trabeculation progressed compared with resorption in both cohorts. In cohort 1, multiple regression analyses showed that the diaphyseal lesion, smaller defect volume, and increased resorption values at 3 months were associated with increased values of resorption 12 months after surgery (R2 = 0.66, p < 0.001). The trabeculation values at 2 months were positively related to the trabeculation values 12 months after surgery (R2 = 0.35, p = 0.002). In cohort 2, the increased resorption values at 2 months and smaller defect volume significantly correlated with the increased resorption values 12 months after surgery (R2 = 0.58, p < 0.001). The ratio from the baseline of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen at 3 months was negatively associated with the trabeculation values 12 months after surgery (R = − 0.791, p = 0.004). Evaluation of radiographic images and bone metabolic markers in the early postoperative period may predict the healing status at 12 months postoperatively in the defects followed by Affinos filling.

DOI： 10.1038/s41598-022-20359-5

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

Urakawa, H; Nagano, A; Machida, R; Tanaka, K; Kataoka, T; Sekino, Y; Nishida, Y; Takahashi, M; Kunisada, T; Kawano, M; Yoshida, Y; Takagi, T; Sato, K; Hiruma, T; Hatano, H; Tsukushi, S; Sakamoto, A; Akisue, T; Hiraoka, K; Ozaki, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 52 ( 9 ) page： 1021 - 1028 2022.9

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

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

DOI： 10.1093/jjco/hyac071

A phase III study comparing methotrexate (M), adriamycin (A) and cisplatin (P) with MAP plus ifosfamide (MAP plus IF) for the treatment of osteosarcoma: JCOG0905 Reviewed

Hiraga, H; Machida, R; Kawai, A; Matsumoto, Y; Yonemoto, T; Nishida, Y; Nagano, A; Ae, K; Yoshida, S; Asanuma, K; Toguchida, J; Huruta, D; Nakayama, R; Akisue, T; Hiruma, T; Morii, T; Tanaka, K; Kataoka, T; Fukuda, H; Ozaki, T

ANNALS OF ONCOLOGY Vol. 33 ( 7 ) page： S1225 - S1225 2022.9

Short-term clinical outcomes of Kyocera Modular Limb Salvage System designed cementless stems for the endoprosthetic reconstruction of lower extremities: a Japanese Musculoskeletal Oncology Group multi-institutional study Reviewed Open Access

Tsukushi, S; Nishida, Y; Hirose, T; Nakata, E; Nakagawa, R; Nakamura, T; Imanishi, J; Nagano, A; Tamiya, H; Ueda, T

BMC CANCER Vol. 22 ( 1 ) page： 781 2022.7

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

Background: The high rate of aseptic loosening of cemented stems has led to their frequent use in endoprosthetic reconstruction. However, problems, such as stem breakage and stress shielding at the insertion site, remain. The Japanese Musculoskeletal Oncology Group (JMOG) has developed Kyocera Modular Limb Salvage System (KMLS) cementless stems with a unique tapered press-fit and short fixation design. This study aimed to clarify the short-term postoperative outcomes of this prosthesis and validate the stem design. Methods: One hundred cases of KMLS cementless stems (51 male patients; median age, 49 years; mean follow-up period, 35 months), with a minimum follow-up of 2 years, for the proximal femur (PF), distal femur (DF), and proximal tibia were prospectively registered for use. Prosthesis survival, complication rates, postoperative functional, and radiographical evaluation were analyzed. Complications or failures after insertion of the KMLS endoprostheses were classified into five types and functional results were analyzed according to the MSTS scoring system at postoperative 1 year. The diaphyseal interface and anchorage were graded by the ISOLS system at postoperative 2 years. Results: The overall prosthesis survival rates at 2 and 4 years were 88.2 and 79.6%, respectively. The prosthesis-specific survival rate excluding infection and tumor recurrence was 90.2 and 87.9%, respectively. Younger age (p = 0.045) and primary tumor (p = 0.057) were associated with poor prognosis of prosthesis-specific survival excluding infection and tumor recurrence. Complications were observed in 31 patients, 13 patients underwent revision surgery. The mean MSTS functional score at 1 year postoperatively was 68%. Early implant loosening was significantly more common in the DF (p = 0.006) and PF/DF straight stem (p = 0.038). The ISOLS radiographic evaluation at 2 years after surgery revealed good bone remodeling and anchorage in most cases (bone remodeling: 90% / excellent and good, anchorage: 97% / excellent and good). Conclusions: Tumor endoprosthesis long-term fixation to the diaphysis of the lower extremity remains challenging. The KMLS cementless stem with a unique tapered press fit design showed good short-term results in maintaining bone stock. To prevent early loosening, a curved stem should be used in PF and DF, but long-term follow-up is necessary.

DOI： 10.1186/s12885-022-09873-x

Efficacy of auranofin as an inhibitor of desmoid progression Reviewed Open Access

Ito, K; Nishida, Y; Hamada, S; Shimizu, K; Sakai, T; Ohkawara, B; Alman, BA; Enomoto, A; Ikuta, K; Koike, H; Zhang, JR; Ohno, K; Imagama, S

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 11918 2022.7

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

Anticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were screened. An identified drug was subjected to the investigation of apoptotic effects on DF cells with analysis of Caspase 3/7 activity. Expression of β-catenin was evaluated with western blot analysis, and immunofluorescence staining. Effects of the identified drug on in vivo DF were analyzed using Apc1638N mice. Auranofin was identified as a drug that effectively inhibits the proliferation of DF cells. Auranofin did not affect Caspase 3/7 activity compared to control. The expression level of β-catenin protein was not changed regardless of auranofin concentration. Auranofin effectively inhibited the development of tumorous tissues by both oral and intraperitoneal administration, particularly in male mice. Auranofin, an anti-rheumatic drug, was identified to have repositioning effects on DF. Since auranofin has been used for many years as an FDA-approved drug, it could be a promising drug with fewer side effects for DF.

DOI： 10.1038/s41598-022-15756-9

Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi-institutional study Reviewed Open Access

Kozawa, E; Nishida, Y; Kawai, A; Hayakawa, K; Setsu, N; Kawashima, H; Iwata, S; Tsuchiya, H; Tsukushi, S; Takenaka, S; Imanishi, J; Baba, I; Nagano, A; Morii, T; Shirai, T; Shimizu, K; Kawano, H

CANCER SCIENCE Vol. 113 ( 7 ) page： 2397 - 2408 2022.7

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

Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease-specific survival (DSS) and disease-free survival (DFS), and prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5-year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5-year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high-grade chondrosarcoma, particularly for those with DDCS.

DOI： 10.1111/cas.15382

Recurrent genomic patterns of MPNST evolution correlate with clinical outcome Reviewed

Ciriano, IC; Steele, CD; Piculell, K; Al-Ibraheemi, A; Eulo, V; Bui, MM; Chatzipli, A; Dickson, BC; Borcherding, DC; Galor, A; Hart, J; Feber, A; Jones, KB; Jordan, JT; Kim, RH; Lindsay, D; Miller, C; Nishida, Y; Serrano, J; Ullrich, NJ; Viskochil, D; Wang, X; Snuderl, M; Proszek, P; Park, PJ; Flanagan, AM; Hirbe, AC; Pillay, N; Miller, DT

CANCER RESEARCH Vol. 82 ( 12 ) 2022.6

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

Yamashita, K; Funauchi, Y; Hayakawa, K; Ae, K; Matsumoto, S; Ikuta, K; Nishida, Y; Ueno, T; Shimoyama, Y; Hiruta, N; Machinami, R; Kawachi, H; Takeuchi, K

VIRCHOWS ARCHIV Vol. 480 ( 6 ) page： 1269 - 1275 2022.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Virchows Archiv

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

DOI： 10.1007/s00428-021-03218-y

Surgical treatment for extremity rhabdomyosarcoma: longitudinal national questionnaire survey in Japan Reviewed

Nishida, Y; Kawai, A

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 52 ( 4 ) page： 362 - 369 2022.4

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

Background: Extremity rhabdomyosarcoma differs from other soft tissue sarcomas, being highly sensitive to chemotherapy and radiotherapy and having a high rate of metastasis to lymph nodes. Therefore, the treatment modality differs from that of other soft tissue sarcomas. The purpose of this study was to conduct a longitudinal questionnaire survey of orthopedic oncologists in charge of surgical treatment for extremity rhabdomyosarcoma in Japan to determine whether the treatment modality chosen here is in line with the international and national treatment ones. Methods: Questionnaire surveys were conducted in 2012 and 2019 to orthopedic oncologists of Japanese Orthopaedic Association and Japanese Musculoskeletal Oncology Group. Results: Responses were obtained from 80 facilities and 76 facilities, respectively. Fewer than 50% of the facilities treated one or more patients a year in both years. Many facilities first performed diagnostic biopsy, but most did not perform pretreatment re-excision. The number of facilities that provided radiotherapy in addition to surgery increased significantly from 2012 to 2019 (P = 0.028), but it was still 21% in 2019. The number of facilities performing excision and lymph node dissection was 19% in both 2012 and 2019, which was a very low result without improvement. The departments responsible for follow-up have been changed to pediatrics and orthopedic oncology in tandem (P = 0.0004). Conclusions: Radiotherapy and pathological evaluation of lymph nodes are important for improving the prognosis of patients with extremity rhabdomyosarcoma. It is necessary to continue and develop more efficient educational activities on the appropriate medical treatment modalities for extremity RMS.

DOI： 10.1093/jjco/hyab206

Effects of Neuromuscular Electrical Stimulation on Lower Limb Muscle Strength After Living Donor Liver Transplant: A Case-Control Study Reviewed

Hattori, K; Mizuno, Y; Ogura, Y; Inoue, T; Nagaya, M; Jobara, K; Kurata, N; Nishida, Y

TRANSPLANTATION PROCEEDINGS Vol. 54 ( 3 ) page： 749 - 754 2022.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Transplantation Proceedings

Background: Early mobilization after liver transplant (LT) plays an important role in postoperative recovery and complication prevention; however, patients undergoing LT cannot achieve early mobilization because of mechanical ventilation and poor preoperative physical performance. We investigated the effect of neuromuscular electrical stimulation (NMES) on lower limb muscle strength after living donor liver transplant (LDLT). Methods: Adult patients who underwent LDLT between December 2016 and January 2019 at a university hospital were recruited. A consecutive series of patients who underwent LDLT without NMES therapy before the clinical trial (April 2014-May 2016) were enrolled as the non-NMES (control) group. Patients in the NMES group received NMES on the quadriceps muscles starting 1 day post LDLT for 4 weeks. The study was conducted in accordance with the Declaration of Helsinki, and all patients provided informed consent. Results: Twenty-four patients in the NMES group and 16 patients in the non-NMES group were analyzed. There was no significant difference between groups regarding changes in any outcome. Conclusions: The application of NMES in patients with LDLT did not yield greater improvement of muscle strength, functional capacity, activities of daily living, or length of hospital stay 4 weeks postoperatively compared with the control group. However, developing a novel NMES device and confirming whether additional NMES is effective for other body areas may yield different results.

DOI： 10.1016/j.transproceed.2022.01.028

Long-Term Results of Kyocera Modular Limb Salvage System after Resection of Tumors in the Distal Part of the Femur: Report from Japanese Musculoskeletal Oncology Group Study Reviewed

Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase Reviewed Open Access

Koike, H; Nishida, Y; Shinomura, T; Ohkawara, B; Ohno, K; Zhuo, LS; Kimata, K; Ushida, T; Imagama, S

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 23 ( 8 ) 2022.4

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

KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (p = 0.006). Ipriflavone increased the HA accumulation and suppressed the MMP1 and MMP3 expression on TNF-α stimulated FLS. In vivo, Ipriflavone significantly improved the symptoms and reduced the serum concentrations of HA. Conclusions: We identified Ipriflavone, which has inhibitory effects on KIAA1199 activity. Ipriflavone may be a therapeutic candidate based on its reduction of KIAA1199 activity in inflammatory arthritis.

DOI： 10.3390/ijms23084089

Nakamura Tomoki, Matsumine Akihiko, Toda Yu, Takenaka Satoshi, Outani Hidetatsu, Fujiwara Tomohiro, Nishida Yoshihiro, Tsukushi Satoshi, Tomita Masato, Torigoe Tomoaki, Tome Yasunori, Kawamoto Teruya, Kito Munehisa, Shinohara Naohiro, Sudo Akihiro, Kawano Hirotaka

Cancers Vol. 14 ( 4 ) page： 1 - 11 2022.2

Language：English Publishing type：Research paper (scientific journal)

Background: The distal femur is a common site of bone tumors. After surgical resection, prosthetic replacement is a major reconstruction method. We aimed to elucidate the long-term outcomes of the Kyocera Modular Limb Salvage (KMLS) systems after resection of tumors in the distal part of the femur. Methods: Between 1998 and 2014, 125 patients were treated at 14 institutions. There were 59 males and 66 females, with a mean age of 35 years. The mean follow-up period was 132 months. Results: There had been 65 additional surgeries, including 56 revisions and 9 amputations: 15 for aseptic loosening, 14 for stem breakage, 13 for deep infection, 13 for rotator-hinge bushing failure, 5 for local recurrence, and 5 for others. Implant survival rates at 10 and 15 years were 58.5% and 39.4%. The cumulative incidence of 15-year revision for femoral stem breakage was 31.7% in patients with cementless fixation. The 15-year cumulative incidence of revision for aseptic loosening was 19.8% in patients with cement fixation. Conclusions: KMLS systems represent a reliable system with long-term results. Stem breakage should be considered in patients with cementless and/or smaller femoral stem sizes. Aseptic loosening should be considered in patients with cement systems after 10 years.

Clinical outcome in patients who underwent amputation due to extremity soft tissue sarcoma: Tokai Musculoskeletal Oncology Consortium study Reviewed

Hagi, T; Nakamura, T; Nagano, A; Koike, H; Yamada, K; Aiba, H; Fujihara, N; Wasa, J; Asanuma, K; Kozawa, E; Ishimura, D; Kawanami, K; Izubuchi, Y; Shido, Y; Sudo, A; Nishida, Y

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 52 ( 2 ) page： 157 - 162 2022.2

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

Background: Soft tissue sarcomas are a diverse group of rare malignant tumours, mostly occurring in the lower extremities. Amputations are necessary for achieving local control when the soft tissue sarcomas are too large and/or have neurovascular involvement. Patients who require amputation have a poorer prognosis than those who undergo limb-salvage surgery. Patients and Methods: We investigated the tumour characteristics and the clinical outcomes in 55 patients with primary soft tissue sarcomas, who underwent amputation. We excluded patients with amputation performed distal to the wrist or ankle joints and those with recurrent soft tissue sarcomas. Results: The mean tumour size was 11.1 cm. Hip disarticulation was performed in 6 patients, 20 underwent above the knee amputation, 8 underwent knee disarticulation and 12 underwent below the knee amputation. Shoulder disarticulation was performed in three patients, five underwent above the elbow amputation, and one underwent below the elbow amputation. The 5-year disease-specific survival rate was 52.8%. The 5-year recurrence-free survival rate and 5-year metastasis-free survival rates were 90.1% and 38.5%, respectively. Larger tumour size, age and the distant metastases at first presentation were predictors of poor prognosis for survival in multivariate analysis. Twenty-eight patients could walk using artificial limbs. The level of amputation (above versus below the knee) showed a significant difference in achieving independent gait. Conclusion: Amputation is a useful treatment option for achieving local control in patients with large soft tissue sarcomas. Patients had an opportunity of walking, especially for those who underwent below the knee amputation.

DOI： 10.1093/jjco/hyab184

Diffusion-Weighted Magnetic Resonance Imaging Improves the Accuracy of Differentiation of Benign from Malignant Peripheral Nerve Sheath Tumors Reviewed Open Access

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

WORLD NEUROSURGERY Vol. 157 page： E207 - E214 2022.1

Language：English Publishing type：Research paper (scientific journal) Publisher：World Neurosurgery

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

DOI： 10.1016/j.wneu.2021.09.130

薬物療法の適応と限界1・2　デスモイドに対する薬物治療 Reviewed

西田佳弘, 酒井智久, 生田国大, 小池宏

日本整形外科学会雑誌 Vol. 96 page： 488 - 493 2022

後腹膜発生軟部肉腫に対する治療戦略 Reviewed

生田国大, 西田佳弘

整形・災害外科 Vol. 65 page： 289 - 294 2022

Successful treatment with denosumab for pelvic fibrous dysplasia: A case report and review of the literature. Reviewed Open Access

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

Medicine (Baltimore). Vol. 100 ( 49 ) page： e28138 - e28138. 2021.12

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

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

KNEE Vol. 33 page： 102 - 109 2021.12

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

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

DOI： 10.1016/j.knee.2021.09.006

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review Reviewed Open Access

Emori, M; Matsumoto, Y; Murahashi, Y; Yoshida, M; Nishida, Y

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 4 ) page： 673 - 681 2021.11

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

The efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the ef-ficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords “Fibromatosis, aggressive” and “Cyclooxygenase inhibitors.” Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers’ manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

DOI： 10.18999/nagjms.83.4.673

Trends in diagnostic and therapeutic strategies for extra-abdominal desmoid-type fibromatosis: Japanese musculoskeletal oncology group questionnaire survey Reviewed Open Access

Murase, F; Nishida, Y; Hamada, S; Sakai, T; Shimizu, K; Ueda, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 51 ( 11 ) page： 1615 - 1621 2021.11

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

Objective: The mainstay of treatment modality for extra-abdominal desmoid-type fibromatosis (DF) has shifted from surgery, which often impairs ADL/QOL, to conservative treatment including active surveillance. In the present study, we conducted a longitudinal survey on the diagnosis and treatment of DF at facilities belonging to the Japanese Musculoskeletal Oncology Group, which is a research group of facilities specializing in the treatment of bone and soft tissue tumors in Japan to clarify the transition of medical care for extra-abdominal DF. Methods: The same questionnaire was administered in 2015 and 2018, and responses were obtained from 46 (69%) of 67 facilities and 42 (53%) of 80 facilities in 2015 and 2018, respectively. Results: Although immunostaining for β-catenin was often used for the pathological diagnosis in both 2015 and 2018, CTNNB1 mutation analysis was not performed either in 2015 or in 2018. As for the treatment strategy for resectable cases, surgical treatment including wide resection was selected at 11 facilities (24% of respondents) in 2015, and further decreased to 5 facilities (12%) in 2018. Conservative treatment with active surveillance or medical treatment was the most common treatment for both resectable and difficult-to-resect cases. COX-2 inhibitors and tranilast were often used in the drug treatment of both resectable and difficult-to-resect cases. Few facilities provided radiotherapy, methotrexate and vinblastine, or DOX-based chemotherapy for refractory cases in both 2015 and 2018. Conclusions: A good trend was found in the questionnaire survey. It will be further necessary to disseminate clinical practice guidelines to physicians more widely, and to have them understand and implement the most up-to-date medical practice strategies for this rare disease.

DOI： 10.1093/jjco.hyab146

Untitled Reply Reviewed Open Access

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

ARTHRITIS & RHEUMATOLOGY Vol. 73 ( 11 ) page： 2148 - 2149 2021.11

Less-invasive fascia-preserving surgery for abdominal wall desmoid Reviewed Open Access

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

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

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

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

DOI： 10.1038/s41598-021-98775-2

Efficacy and Safety of Diclofenac-Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan Reviewed Open Access

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

ARTHRITIS & RHEUMATOLOGY Vol. 73 ( 9 ) page： 1646 - 1655 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Arthritis and Rheumatology

Objective: To confirm the efficacy and safety of intraarticular (IA) injection of diclofenac covalently linked to hyaluronic acid (diclofenac etalhyaluronate [DF-HA]; ONO-5704/SI-613) in patients with knee osteoarthritis (OA). Methods: In a phase III multicenter, randomized, double-blind, placebo-controlled trial, eligible subjects ages 40–75 years with symptomatic knee OA (Kellgren/Lawrence score of 2 or 3) were randomly assigned to receive IA injections of DF-HA 30 mg or placebo (citric acid–sodium citrate buffered solution; 1:1) once every 4 weeks for 20 weeks (a total of 6 injections). Subjects were followed up for 24 weeks. The primary end point was the mean change from baseline to 12 weeks in Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC) pain subscale scores, measured on a 100-mm visual analog scale. Safety was evaluated by adverse event monitoring. Results: All 440 subjects received investigational products (220 received placebo and 220 received DF-HA). The full analysis set and safety population comprised 438 subjects (220 in the placebo group and 218 in the DF-HA group) and 440 subjects, respectively. At 12 weeks, subjects receiving DF-HA showed significant improvement from baseline in the WOMAC pain subscale score (–23.2 mm) compared to subjects receiving placebo (−17.1 mm), with a difference of −6.1 mm (95% confidence interval −9.4, −2.8; P < 0.001). The difference between groups was significant as early as week 1, and a difference was maintained for 24 weeks, although the difference at week 24 was not significant. Anaphylactic reactions were observed in 2 subjects receiving DF-HA. Conclusion: Our findings indicate that treatment with DF-HA results in significant improvement in the WOMAC pain subscale score compared to placebo over 12 weeks. Anaphylactic reactions were observed, and further safety evaluation is needed.

DOI： 10.1002/art.41725

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

Ota, T; Nishida, Y; Ikuta, K; Tsukushi, S; Yamada, K; Kozawa, E; Urakawa, H; Imagama, S

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

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

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

DOI： 10.1038/s41598-021-96795-6

Spontaneous Regression of Brown Tumor in a Patient Treated With Peritoneal Dialysis Reviewed Open Access

Ito, K; Ikuta, K; Nishida, Y; Sakai, T; Imagama, S

CUREUS JOURNAL OF MEDICAL SCIENCE Vol. 13 ( 8 ) page： e17078 2021.8

Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study Reviewed Open Access

Aiba, H; Ikuta, K; Asanuma, K; Kawanami, K; Tsukushi, S; Matsumine, A; Ishimura, D; Nagano, A; Shido, Y; Kozawa, E; Yamada, K; Wasa, J; Kimura, H; Sakai, T; Murakami, H; Sakai, T; Nakamura, T; Nishida, Y

CANCERS Vol. 13 ( 15 ) 2021.8

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

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

DOI： 10.3390/cancers13153901

A Novel Technique to Lengthen the Reverse Latissimus Dorsi Muscle Flap Arc Reviewed

Takanari, K; Nakamura, Y; Uchibori, T; Nakamura, R; Ebisawa, K; Kambe, M; Urakawa, H; Nishida, Y; Kamei, Y

PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN Vol. 9 ( 7 ) page： e3525 2021.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Plastic and Reconstructive Surgery Global Open

Reconstruction of the lower lumbar region is challenging for surgeons due to limited locoregional flap choices. The latissimus dorsi muscle flap is a mainstay for this area; however, there are several limitations, including that the dominant thoracodorsal artery and vein pedicle-based flaps are not reachable for reconstruction of the lumbar region, while perforator of intercostal artery and veins pedicle-based reverse latissimus dorsi (RLD) flap mobility is limited by including multiple perforators. Here, we describe a novel operative technique that lengthens the rotation arc of RLD muscle flaps. The surgical technique is as follows: RLD is elevated based on lower perforator of intercostal artery and veins (usually including two of the eighth-11th perforators); thoracodorsal artery and vein are ligated; and the flap is mobilized toward the defect. When RLD was not reachable to the defect, the far aspect of the intercostal artery and vein from the defect was ligated and the perforator was elevated with the near aspect of the intercostal artery and vein from intercostal space. Because the intercostal space measured between approximately 3 cm and 4 cm, this dissection gained 3-4 cm of rotational arc per intercostal space. Moreover, because the lower ribs follow a medio-cranial to latero-caudal direction, this dissection enabled the flap to extend latero-caudally or medio-cranially while maintaining its blood supply. Other applications using this technique may involve expanding the RLD flap arc caudally, ventrally, and ipsilaterally. We believe this new technique provides a reliable alternative for lower back reconstruction.

DOI： 10.1097/GOX.0000000000003525

A comparison of the usefulness of nuclear beta-catenin in the diagnosis of demoid-type fibromatosis among commonly used anti-beta-catenin antibodies. Reviewed

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital Reviewed Open Access

Nishida, Y; Ikuta, K; Natsume, A; Ishihara, N; Morikawa, M; Kidokoro, H; Muramatsu, Y; Nonobe, N; Ishizuka, K; Takeichi, T; Kanbe, M; Mizuno, S; Imagama, S; Ozaki, N

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

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

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

DOI： 10.1038/s41598-021-91345-6

Yamada Y, Hirata M, Sakamoto A, Noguchi T, Ito K, Nishida Y, Matsuda S, Haga H

Pathol Int. Vol. 71 ( 6 ) page： 392 - 399 2021.6

Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer Reviewed Open Access

Tanaka, S; Ozeki, N; Mizuno, Y; Nakajima, H; Hattori, K; Inoue, T; Nagaya, M; Fukui, T; Nakamura, S; Goto, M; Sugiyama, T; Nishida, Y; Chen-Yoshikawa, TF

JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE Vol. 12 ( 3 ) page： 646 - 656 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Cachexia Sarcopenia and Muscle

Background: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. Methods: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). Results: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79–6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27–3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. Conclusions: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

DOI： 10.1002/jcsm.12691

The Prognostic Role of β-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only A Meta-analysis of Individual Patient Data Reviewed Open Access

Timbergen, MJM; Colombo, C; Renckens, M; Kim, HS; van Rosmalen, J; Salas, S; Mullen, JT; Colombo, P; Nishida, Y; Wiemer, EAC; Verhoef, C; Sleijfer, S; Gronchi, A; Grünhagen, DJ

ANNALS OF SURGERY Vol. 273 ( 6 ) page： 1094 - 1101 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Annals of Surgery

Objective:This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients.Summary of Background Data:The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types.Methods:A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used.Results:Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence.Conclusions:Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.

DOI： 10.1097/SLA.0000000000003698

Short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice Reviewed Open Access

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

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

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

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

DOI： 10.1038/s41598-021-86730-0

特集骨粗鬆症-指導に役立つエビデンス紫外線によるビタミンD産生-必要な日照時間と影響因子 Reviewed

西田佳弘, 落合聡史, 牧田和也

総合リハビリテーション Vol. 49 ( 4 ) page： 351 - 355 2021.4

Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up Reviewed Open Access

Nishida, Y; Kano, K; Osato, T; Seo, T

BMC MUSCULOSKELETAL DISORDERS Vol. 22 ( 1 ) page： 233 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Musculoskeletal Disorders

Background: We evaluated the 1-year safety and efficacy of diclofenac etalhyaluronate (DF-HA), a diclofenac-conjugated hyaluronate, in patients with osteoarthritis (OA). Methods: In this multi-centre, open-label, noncomparative phase 3 study in Japan, patients with a diagnosis of knee, shoulder, elbow, hip, or ankle OA received an intra-articular (IA) injection of DF-HA 30 mg every 4 weeks for 1 year (13 times in total). The safety outcomes included treatment-emergent adverse events (TEAEs) and target joint structural changes by X-ray imaging tests. Efficacy outcomes included joint pain scores on an 11-point numerical rating scale. Concomitant use of analgesics was not restricted. Results: Overall, 166 eligible patients were enrolled, comprising knee OA (n = 126) and other OA (n = 40). All TEAEs were experienced by 126/166 patients (75.9%). The incidence of treatment-related TEAEs was not associated with the treatment period. No significant worsening of joint status was observed in X-ray imaging tests at week 52 or at last assessment. The mean joint pain scores (± standard deviation) were 5.9 ± 1.2, 4.9 ± 1.9, and 3.1 ± 2.3 at baseline, and weeks 2 and 52, respectively. Improvement of pain score was observed after the first injection and was maintained until week 52 regardless of knee OA or other joint OA. Conclusions: Repeated IA injections of DF-HA every 4 weeks for 1 year were well tolerated with no clinically significant adverse events indicating they might lead to the long-term improvement of OA symptoms. DF-HA might be a useful treatment for patients with OA. Trial registration number: JapicCTI-183855 (First registered date: 6th February 2018).

DOI： 10.1186/s12891-021-04108-9

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 × 106). 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/cm2, 1,000 J/m2). we set a total of 4 groups (n = 8 per group); vitamin D-repletion without UV irradiation (Vit.D+UV−), vitamin D-repletion with UV irradiation (Vit.D+UV +), vitamin D-deficiency without UV irradiation, (Vit.D−UV−), and vitamin D-deficiency with UV irradiation (Vit.D−UV +). Serum levels of 25(OH)D at 28 and 36 weeks of age were increased in Vit.D−UV+ group as compared with Vit.D−UV− group. Trabecular bone mineral density on micro-CT was higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. In the histological assay, fewer osteoclasts were observed in Vit.D−UV+ group than in Vit.D−UV− group. Grip strength and muscle mass were higher in Vit.D−UV+ group than in Vit.D−UV− group at 36 weeks of age. Signs of severe damage induced by UV irradiation was not found in skin histology. Low energy narrow-range UV irradiation may improve osteosarcopenia associated with vitamin D deficiency in SAMP6.

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

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. Reviewed

A case of retroperitoneal dedifferentiated liposarcoma successfully treated by neoadjuvant chemotherapy and subsequent surgery. Reviewed Open Access

Yokoyama Y, Nishida Y, Ikuta K, Nagino M

Surgical case reports Vol. 6 ( 1 ) page： 105 2020.5

Nishida, Y; Urakawa, H; Nakayama, R; Ozaki, T; Ae, K; Matsumoto, Y; Ando, Y; Kuwatsuka, Y; Ueda, T; Kawai, A

JOURNAL OF CLINICAL ONCOLOGY Vol. 38 ( 15 ) 2020.5

Results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306. Reviewed

Tanaka, K; Machida, R; Kawai, A; Nakayama, R; Tsukushi, S; Asanuma, K; Matsumoto, Y; Hiraga, H; Hiraoka, K; Watanuki, M; Yonemoto, T; Abe, S; Katagiri, H; Nishida, Y; Nagano, A; Suehara, Y; Kataoka, T; Fukuda, H; Ozaki, T; Iwamoto, Y

JOURNAL OF CLINICAL ONCOLOGY Vol. 38 ( 15 ) 2020.5

Type II Respiratory Failure with Systemic Sclerosis/Polymyositis Overlap Syndrome：A Case Report of Successful Respiratory Rehabilitation Therapy

Okada Takashi, Nishida Yoshihiro, Hishida Aika, Sugiyama Junya, Kadono Izumi, Sugiura Hideshi, Konno Suzuna

The Japanese Journal of Rehabilitation Medicine Vol. 57 ( 5 ) page： 468 - 473 2020.5

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Association of Rehabilitation Medicine

Introduction：Respiratory failures are categorized into types I and II. To our knowledge, we report the first case of pulmonary rehabilitation in a patient with systemic sclerosis/polymyositis overlap syndrome who developed type II respiratory failure.Methods：The patient was a 77-year-old woman who had received treatment for systemic sclerosis and polymyositis at another hospital. When she visited our hospital to obtain a second opinion, she suddenly lost consciousness and underwent trachea intubation because of typeⅡrespiratory failure. She received physical therapy on the third day of hospitalization and underwent a tracheotomy on the 16th day. As her thoracic movement was markedly restricted, we started physical training. After she was weaned off from the ventilator on the 43rd day, we performed muscular strength training and aerobic exercise. No exacerbation of CO2 storage was observed even if chest motion training was performed. She was discharged on the 72nd day and advised to wear retina®．Administration of therapeutic drugs such as steroids was maintained at the same dose.Conclusion：Physical therapy, such as chest mobilization, was effective for marked restriction of chest movement in a patient who had both polymyositis and systemic sclerosis.

DOI： 10.2490/jjrmc.18038

Thoracic dumbbell-shaped paraganglioma arising in extra-adrenal area: A case report and literature review. Reviewed

Tsushima M, Imagama S, Ando K, Kobayashi K, Ito K, Matsumoto A, Nishida Y, Ishiguro N

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association Vol. 25 ( 3 ) page： 525 - 528 2020.5

Clinical characteristics and surgical outcomes of retroperitoneal tumors: a comprehensive data collection from multiple departments Reviewed

Sassa, N; Yokoyama, Y; Nishida, Y; Yamada, S; Uchida, H; Kajiyama, H; Nagino, M; Kodera, Y; Gotoh, M

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY Vol. 25 ( 5 ) page： 929 - 936 2020.5

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

Background: There are only a limited number of comprehensive reports for retroperitoneal tumors (RPTs). The aim of this study was to perform an interdepartmental data collection for RPTs and to comprehensively clarify the clinical characteristics of this rare disease. Methods: All patients who were diagnosed with RPT from January 2005 to July 2018 in a single institution were included. The analyzed factors included demographics, clinical features, treatment methods, pathological diagnosis, and prognosis. Results: A total of 422 patients (215 males and 207 females) with primary RPTs were identified. Biopsy for RPT was performed in 180 patients (43%). Among the 422 patients, 239 (57%) underwent surgery. The most common tissue origin was mesodermal (n = 99, 41%), followed by neurogenic (n = 54, 23%), extragonadal (n = 27, 11%), and metastatic tumors (n = 13, 5%). Among the 99 resected mesodermal tumors, the most common pathological subtypes were liposarcoma (n = 55, 56%) and leiomyosarcoma (n = 16, 16%). The long-term outcomes after surgery were analyzed in patients with intermediate and malignant sarcomas (including liposarcoma, leiomyosarcoma, and others combined, n = 71). The 3- and 5-year disease-free survival rates in the intermediate tumors were 68.2% and 54.2%, respectively, whereas those in the malignant tumors were 48.6% and 28.9%, respectively. The 3- and 5-year overall survival rates in the intermediate tumors were 100% and 94.1%, respectively, whereas those in the malignant tumors were 78.4% and 72.8%, respectively (p = 0.009). Conclusions: The clinical manifestations of RPTs were extremely variable. Recurrence after repeating resection is commonly observed in patients with malignant retroperitoneal sarcoma.

DOI： 10.1007/s10147-020-01620-1

症例報告上腕骨近位部の骨表面に発生したグロムス腫瘍の1例 Reviewed

生田国大, 新井英介, 杉浦喬也, 酒井智久, 小池宏, 西田佳弘

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

The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. Reviewed Open Access

Desmoid Tumor Working Group. (Alman B, Nishida Y, et al)

Eur J Cancer. Vol. 127 page： 96 - 107 2020.3

The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma Reviewed Open Access

Heng, M; Gupta, A; Chung, PW; Healey, JH; Vaynrub, M; Rose, PS; Houdek, MT; Lin, PP; Bishop, AJ; Hornicek, FJ; Chen, YL; Lozano-Calderon, S; Holt, GE; Han, I; Biau, D; Niu, XH; Bernthal, NM; Ferguson, PC; Wunder, JS; Ueda, T; Kakunaga, S; Kawai, A; Sugiura, H; Kidani, T; Kunisasa, T; Ozaki, T; Ae, K; Nagano, A; Ohno, T; Hiraoka, K; Yamamoto, N; Tsuchiya, H; Matsumoto, Y; Yanagawa, T; Nakayama, R; Morioka, H; Kubo, T; Simose, S; Yamagami, Y; Yamamoto, T; Kawasaki, M; Torigoe, T; Yazawa, Y; Akiyama, T; Gokita, T; Manabe, J; Kaya, M; Emori, M; Nakamura, T; Matsumine, A; Sugihara, S; Yokouchi, M; Komiya, S; Suehara, Y; Takagi, T; Kawamoto, T; Wasa, J; Yonemoto, T; Ishii, T; Baba, I; Hoshi, M; Hamada, K; Naka, N; Sotobori, T; Araki, N; Okuma, T; Goto, T; Kobayashi, H; Kawano, H; Hosaka, M; Futani, H; Hiraga, H; Nishida, Y; Griffin, A; Razak, ARA; Shultz, DB; Catton, C; Robinson, S; Patel, SR; Lewis, VO; Guadagnolo, BA; DeLaney, T; Wang, HT; Raskin, K; Callan, AK; Henshaw, R; Isler, M; Mottard, S; Chen, WM; Traub, F; Chen, TWW; Turcotte, RE; Davidson, D; Tunn, PU; Loong, H; Ghert, M; Werier, J; Clarkson, P; Abraham, JA

EUROPEAN JOURNAL OF CANCER Vol. 125 page： 130 - 141 2020.1

食道癌術後の心房細動発症が術後経過、身体機能に及ぼす影響 Reviewed

白井祐也, 水野陽太, 清水大, 井上貴行, 岡田貴士, 西田佳弘, 小池聖彦, 永谷元基

理学療法学Supplement Vol. 47S1 ( 0 ) page： C-17_2 - C-17_2 2020

筋力低下に加え、廃用も呈した抗SRP（signal recognition particle）抗体陽性壊死性ミオパチー症例に対する理学療法介入の経験 Reviewed

鄭伃廷, 加古誠人, 柴田篤志, 天草善信, 橋詰淳, 熱田直樹, 勝野雅央, 西田佳弘

理学療法学Supplement Vol. 47S1 ( 0 ) page： F-171_2 - F-171_2 2020

Diagnosis, treatment, and proposal of the new classification system for the severity of desmoid tumors associated with familial adenomatous polyposis Reviewed

Mori Yoshiko, Chikatani Kenichi, Ishida Hideyuki, Yamano Tomoki, Momose Syuji, Tomita Naohiro, Osada Hisato, Nuguruma Naoki, Takayama Tetsuji, Akiyama Yasuki, Hirata Keiji, Nishida Yoshihiro, Ishikawa Hideki

Journal of Hereditary Tumors Vol. 20 ( 2 ) page： 45 - 58 2020

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Hereditary Tumors

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder characterized by multiple colorectal adenomas. Desmoid tumors (DT) are a well-known extracolonic manifestation of FAP that frequently develop in the mesentery, retroperitoneum, and/or abdominal wall in patients
with FAP. DT negatively impact the quality of life and affect survival. Due to their unclear natural course and insufficient data, there is no established evidencebased medical treatment for DT. In this article, we describe the diagnosis and treatment for DT in patients with FAP, and propose a classification system for the severity of FAP-related DT, with the aim of establishing a standard treatment for this condition.

DOI： 10.18976/jsht.20.2_45

大腿部骨・軟部腫瘍患者における患肢温存術後の機能変化に関する報告 Reviewed

栢本あずさ, 加古誠人, 西田佳弘

理学療法学Supplement Vol. 47S1 ( 0 ) page： A-206_1 - A-206_1 2020

【治療選択誌上ディベート（第20回）】デスモイドの治療選択保存治療VS手術　保存治療の立場から Reviewed

西田佳弘

Loco Cure Vol. 6 page： 68 - 71 2020

Integrated exome and RNA sequencing of dedifferentiated liposarcoma 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. 10 ( 1 ) page： 5683 2019.12

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

The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.

DOI： 10.1038/s41467-019-13286-z

Clinical Frailty Scale Score before ICU Admission Is Associated with Mobility Disability in Septic Patients Receiving Early Rehabilitation Reviewed Open Access

Nakajima H., Nishikimi M., Shimizu M., Hayashi K., Inoue T., Nishida K., Takahashi K., Matsui S., Nishida Y., Matsuda N.

Critical Care Explorations Vol. 1 ( 12 ) page： e0066 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Critical Care Explorations

Objectives: To clarify the relationship between mobility disability at the time of discharge from the ICU and clinical factors evaluated at ICU admission in septic patients. Design: A single-center, retrospective, observational study. Setting: Ten-bed, the emergency and medical ICU. Patients: We analyzed the data of septic patients who were admitted to our ICU between September 2012 and September 2016 and received early rehabilitation. Interventions: None. Measurements and Main Results: The patients were categorized into two groups based on their scores on the ICU mobility scale at the time of discharge from the ICU: The mobility disability group (ICU mobility scale score < 9) and the no mobility disability group (ICU mobility scale score ≥ 9). Of the 110 eligible patients, 63 met the inclusion criteria; of these, 46 patients (73%) were classified into the mobility disability group, and 17 patients (27%) were classified into the no mobility disability group. The age (median, 72 vs 64 yr; p = 0.024), prevalence of patients with clinical frailty scale scores of greater than or equal to 5 (54% vs 12%; p = 0.003), Sequential Organ Failure Assessment score (median, 9.0 vs 6.0; p = 0.006) and rate of vasopressin use (26% vs 0%; p = 0.026) were significantly higher in the mobility disability group as compared with the no mobility disability group. Among the candidate variables for which values recorded before/at the time of ICU admission were available, the clinical frailty scale score was identified as the only independent, statistically significant predictor of mobility disability at ICU discharge (odds ratio, 7.77; 95% CI, 1.37-44.21; p = 0.021). The positive predictive value and negative predictive value of clinical frailty scale scores greater than or equal to 5 for mobility disability at ICU discharge were 92.6% and 41.7%, respectively. Conclusions: The clinical frailty scale score was associated with increased mobility disability at ICU discharge in septic patients receiving early rehabilitation.

DOI： 10.1097/CCE.0000000000000066

Treatment Outcome of Patients With Osteosarcoma in Children and Adolescent. A Single Center Retrospective Analysis Reviewed

Akita, N; Sekimizu, M; Hattori, H; Arai, E; Nishida, Y; Horibe, K; Maeda, N

PEDIATRIC BLOOD & CANCER Vol. 66 page： S59 - S59 2019.12

Clinical Features of Thoracic Myelopathy: A Single-Center Study. Reviewed

Ando K, Imagama S, Kobayashi K, Ito K, Tsushima M, Morozumi M, Tanaka S, Machino M, Ota K, Nakashima H, Nishida Y, Ishiguro N.

J Am Acad Orthop Surg Glob Res Rev. Vol. 3 ( 11 ) page： - 2019.11

Outcome of Cancer Clinical Researches Using Heat-Generating Nanoparticles and Novel Concept of its Therapeutic Use Open Access

YAMAMOTO NORIYUKI, MORINO TOMIO, YASUI TAKAHIRO, NAIKI TAKU, KAWAI NORIYASU, ETANI TOSHIKI, KIKUMORI TOYONE, NISHIDA YOSHIHIRO

Thermal Medicine Vol. 35 ( 3 ) page： 23 - 32 2019.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society for Thermal Medicine

Cancer clinical researches using heat-generating nanoparticles have been conducted in four Japanese universities including authors' universities. The nanoparticles were injected intratumorally and its heat generation was induced by external magnetic field irradiation to kill cancer cells. Three kinds of composite magnetites nanoparticles were applied to clinical researches in combination with either types of magnetic field irradiators generating different frequencies. In this paper we reviewed results of these researches with our unpublished data and discussed its potential and further refinement.Critical issues of clinical feasibility were not found in key process of treatment such as nanoparticles injection, magnetites imaging and magnetic field irradiation. A combinational use of magnetite cationic liposomes (MCL) and alternating magnetic field (AMF) irradiator was found to exhibit tumor regression activity without adverse events such as skin burn and histological damages of surrounding normal tissues. However, efficacies were found variable among tumors whose temperature rise was commonly achieved. In order to ensure efficacy, we discussed importance of MCL dosage divided by tumor volume (mg/cm3) and proposed total heat dose divided by tumor volume (J/cm3) as candidate index to control clinical treatments.

DOI： 10.3191/thermalmed.35.23

Dysphagia after C2-7 in situ Posterior Fusion in a Patient with Diffuse Idiopathic Skeletal Hyperostosis: Case Report of a Rare Presentation Open Access

Cilostazol use is associated with FIM cognitive improvement during convalescent rehabilitation in patients with ischemic stroke: a retrospective study Reviewed Open Access

Senda, J; Ito, K; Kotake, T; Kanamori, M; Kishimoto, H; Kadono, I; Nakagawa-Senda, H; Wakai, K; Katsuno, M; Nishida, Y; Ishiguro, N; Sobue, G

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 81 ( 3 ) page： 359 - 373 2019.8

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

Cilostazol is a phosphodiesterase III-inhibiting antiplatelet agent that is often used to prevent stroke and peripheral artery disease, and its administration has shown significant improvements for cognitive impairment. We investigate the potential of cilostazol for reducing or restoring cognitive decline during convalescent rehabilitation in patients with non-cardioembolic ischemic stroke. The study sample included 371 consecutive patients with lacunar (n = 44) and atherothrombosis (n = 327) subtypes of non-cardioembolic ischemic stroke (224 men and 147 women; mean age, 72.9 ± 8.1 years) who were required for inpatient convalescent rehabilitation. Their medical records were retrospectively surveyed to identify those who had received cilostazol (n = 101). Patients were grouped based on cilostazol condition, and Functional Independence Measure (FIM) scores (total and motor or cognitive subtest scores) were assessed both at admission and discharge. The gain and efficiency in FIM cognitive scores from admission to discharge were significantly higher in patients who received cilostazol than those who did not (p = 0.047 and p = 0.035, respectively); we found no significant differences in other clinical factors or scores. Multiple linear regression analysis confirmed that cilostazol was a significant factor in FIM cognitive scores at discharge (β = 0.041, B = 0.682, p = 0.045); the two tested dosages were not significantly different (100 mg/day, n = 43; 200 mg/day, n = 58). Cilostazol can potentially improve cognitive function during convalescent rehabilitation of patients with non-cardioembolic ischemic stroke, although another research must be needed to confirm this potential.

DOI： 10.18999/nagjms.81.3.359

Okada Takashi, Hishida Aika, Ando Kei, Tsushima Mikito, Kobayashi Kazuyoshi, Machino Masaaki, Morozumi Masayoshi, Tanaka Satoshi, Ota Kyotaro, Nishida Yoshihiro, Imagama Shiro, Kadono Izumi, Ito Kenyu, Ishiguro Naoki

Spine Surgery and Related Research Vol. 3 ( 3 ) page： 270 - 273 2019.7

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

生田国大, 浦川浩, 大田剛広, 新井英介, 西田佳弘, 酒井智久

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

誌上シンポジウム骨軟部腫瘍の薬物治療アップデートデスモイドに対する薬物治療 Reviewed

西田佳弘

臨床整形外科 Vol. 54 ( 7 ) page： 697 - 702 2019.7

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

Nishida, Y; Sakai, T; Shimizu, K; Urakawa, H; Arai, E; Ikuta, K; Ando, Y; Ishiguro, N

JOURNAL OF CLINICAL ONCOLOGY Vol. 37 ( 15 ) 2019.5

A randomized phase III trial of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group Study JCOG1610 Reviewed

Urakawa, H; Mizusawa, J; Tanaka, K; Eba, J; Hiraga, H; Kawai, A; Nishida, Y; Hosaka, M; Iwamoto, Y; Fukuda, H; Ozaki, T

JAPANESE JOURNAL OF CLINICAL ONCOLOGY Vol. 49 ( 4 ) page： 379 - 382 2019.4

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

A randomized phase III trial was planned to commence in October 2017. Resectable giant cell tumor of bone (GCTB) without possible postoperative large bone defect has been treated by curettage with local adjuvant treatment, with the local recurrence rate found to be as high as 24.6-30.8%. The aim of this study is to confirm the superiority of preoperative denosumab for patients with GCTB without possible postoperative large bone defect. A total of 106 patients will be accrued from 34 Japanese institutions over 5 years. The primary endpoint is relapse-free survival (RFS). Secondary endpoints include overall survival, joint-preserved survival, local RFS, metastasis-free survival, adverse events, serious adverse events, surgical and postoperative complications, and discontinuation of denosumab. This trial is conducted by the Bone and Soft Tissue Tumor Study Group in the Japan Clinical Oncology Group and has been registered in the UMIN Clinical Trials Registry as UMIN000029451 .

DOI： 10.1093/jjco/hyz004

Fusion surgery with instrumentation following carbon ion radiotherapy for primary lumbar tumors: A case series Reviewed Open Access

Ando, K; Kobayashi, K; Machino, M; Ota, K; Morozumi, M; Tanaka, S; Imai, R; Nishida, Y; Ishiguro, N; Imagama, S

JOURNAL OF CLINICAL NEUROSCIENCE Vol. 62 page： 264 - 268 2019.4

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

Carbon-ion radiotherapy (CIRT) is a useful modality for treatment of primary spinal sarcoma, but osteonecrosis after CIRT may cause pseudoarthrosis that can make subsequent reconstruction surgery difficult. The patients were a 68-year-old man (case 1), a 30-year-old woman (case 2), and a 49-year-old man (case 3) with lumbar lesions. After CIRT, cases 1 and 3 were treated with instrumented spondylectomy and case 2 underwent posterior decompression and instrumentation surgery. Cases 1 and 2 required several salvage procedures because of failure of instrumentation (rod breakage) before bone union was achieved. After multiple revision surgeries, these cases did achieve bone union without tumor recurrence. In contrast, in case 3, only spondylectomy using a pedicle screw system at 20 months after CIRT was required for fusion. At follow-up 11 years postoperatively, CT showed bone union with invasion of autograft bone from the iliac crest into adjacent vertebra. Collapse or a finding of viable tumor cells after CIRT requires surgery such as spondylectomy with reconstruction. Instrumented fixation following CIRT for a lumbar primary tumor should be performed with multilevel anterior support using a sufficient amount of bone graft in posterior fusion levels.

DOI： 10.1016/j.jocn.2019.01.001

Successful treatment of a recurrent chest wall desmoid tumor with cyclooxygenase-2 inhibitors. Reviewed Open Access

Kaiho T, Nakajima T, Nishida Y, Yoshino I.

J Thorac Cardiovasc Surg. Vol. 157 ( 3 ) page： E195 - E197 2019.3

Is immunohistochemical staining for β-catenin the definitive pathological diagnostic tool for desmoid-type fibromatosis? A multi-institutional study Reviewed Open Access

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

HUMAN PATHOLOGY Vol. 84 page： 155 - 163 2019.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Human Pathology

Immunohistochemical staining with anti–β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatoses (DFs). In recent years, specific gene mutation (CTNNB1) analysis has also been reported to be useful for diagnosis of DF; however, the association between CTNNB1 mutation status and immunohistochemical staining pattern of β-catenin is rarely reported. The purposes of this study are to clarify the relationship of the staining pattern of β-catenin with the CTNNB1 mutation status and various clinical variables, and to investigate the significance of immunohistochemical staining of β-catenin in cases diagnosed as DF. Between 1997 and 2017, 104 cases diagnosed as DF from 6 institutions in Japan were enrolled in this study: Nagoya University, National Cancer Center Hospital, Niigata University, Okayama University, Kyushu University, and Cancer Institute Hospital. For all cases, immunohistochemical staining of β-catenin and gene mutation analysis of CTNNB1 were performed. Of 104 cases, 87 (84%) showed nuclear staining of β-catenin, and 95 (91%) showed positive staining in the cytoplasm. The proportion of cases showing strong nuclear staining of β-catenin was significantly higher in the cases with S45F than in those with T41A or wild type. The proportion of cases stained strongly in the cytoplasm rather than in the nucleus was significantly higher in the group of T41A than that of S45F or wild type. Among 17 cases in which nuclear immunostaining was absent, CTNNB1 mutation was observed in 5 cases (29.4%). There were unignorable cases of DF with negative β-catenin immunostaining despite a definitive clinical and pathological diagnosis of DF and/or positive CTNNB1 mutation.

DOI： 10.1016/j.humpath.2018.09.018

Wave Change of Intraoperative Transcranial Motor-Evoked Potentials During Corrective Fusion for Syndromic and Neuromuscular Scoliosis. Reviewed

名古屋大学医学部附属病院リハビリテーション科

西田佳弘

Vol. 56 ( 1 ) page： 69 - 70 2019.1

Ando K, Kobayashi K, Ito K, Tsushima M, Morozumi M, Tanaka S, Machino M, Ota K, Nishida Y, Ishiguro N, Imagama S

Operative neurosurgery (Hagerstown, Md.) Vol. 16 ( 1 ) page： 53 - 58 2019.1

Clinical Benefit of Preoperative Exercise and Nutritional Therapy for Patients Undergoing Hepato-Pancreato-Biliary Surgeries for Malignancy Reviewed

Nakajima, H; Yokoyama, Y; Inoue, T; Nagaya, M; Mizuno, Y; Kadono, I; Nishiwaki, K; Nishida, Y; Nagino, M

ANNALS OF SURGICAL ONCOLOGY Vol. 26 ( 1 ) page： 264 - 272 2019.1

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

Background: The impact of prehabilitation on physical fitness and postoperative course after hepato-pancreato-biliary (HPB) surgeries for malignancy is unknown. The current study aimed to investigate the effect of preoperative exercise and nutritional therapies on nutritional status, physical fitness, and postoperative outcomes of patients undergoing an invasive HPB surgery for malignancy. Methods: Patients who underwent open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were subjected to prehabilitation. Patients before the introduction of prehabilitation were included as historical control subjects for 1:1 propensity score-matching (no-prehabilitation group). The preoperative nutritional status and postoperative course were compared between the two groups. Results: The prehabilitation group consisted of 76 patients scheduled to undergo HPB surgeries for malignancy. An identical number of patients were selected as the no-prehabilitation group after propensity score-matching. During the waiting period, serum albumin levels were significantly deteriorated in the no-prehabilitation group, whereas this index did not deteriorate or even improved in the prehabilitation group. By performing prehabilitation, a 6-min walk distance and total muscle/fat ratio were significantly increased during the waiting period. Although the overall incidence of postoperative complications did not differ between the two groups, the postoperative hospital stay was shorter in the prehabilitation group than in the no-prehabilitation group (median, 23 vs 30 days; p = 0.045). Conclusion: The introduction of prehabilitation prevented nutritional deterioration, improved physical fitness before surgery, and shortened the postoperative hospital stay for the patients undergoing HPB surgeries for malignancy.

DOI： 10.1245/s10434-018-6943-2

Thoracic spinal cord injury without major bone injury associated with ossification of the ligamentum flavum Reviewed Open Access

Machino, M; Imagama, S; Ito, K; Ando, K; Kobayashi, K; Kato, F; Nishida, Y; Ishiguro, N

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 24 ( 1 ) page： 174 - 177 2019.1

軟部肉腫広範切除のため大腿四頭筋腱合併切除後に膝伸展機構の再建を行い、装具なしで歩行を獲得した症例 Reviewed

神山卓史, 加古誠人, 森友洋, 髙木優衣, 寺井千晶, 栗谷彩, 白井祐也, 新井英介, 門野泉, 西田佳弘

理学療法学Supplement Vol. 46S1 ( 0 ) page： H2-114_1 - H2-114_1 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：公益社団法人日本理学療法士協会

【症例紹介】四肢の軟部肉腫に対する手術では患肢温存率は増加しており、術後の機能再獲得に関しても向上が望まれている。一方で他の整形外科疾患と異なり、手術により切除される組織や再建方法、喪失あるいは残存する機能が患者ごとに異なっているため、リハビリテーションも個々の症例に応じた対応が必要となる。　今回我々は、大腿軟部肉腫に対する広範切除として大腿四頭筋腱を合併切除した後に遊離筋皮弁により再建し、術後の綿密な管理下での積極的な筋力トレーニングにより膝伸展機能を再獲得し、装具を使用せずに片松葉杖歩行を早期に実現した症例を経験したのでこれを報告する。　50代女性、身長151cm、体重46.6kg。既往歴に子宮頸がんを認め、入院前のADLは全自立レベルであった。Ｘ-6ヵ月に右大腿部に腫瘤を触知し、Ｘ-3ヵ月に他院にて右大腿遠位部腫瘤に対して単純摘出術施行された。その後の病理診断にて末分化多形肉腫と診断され、Ｘ-1ヵ月に当院を初診し、Ｘ日に追加広範切除術施行された。【評価とリーズニング】　広範切除により、大腿四頭筋の遠位部は、膝蓋骨停止部から近位10cmほどまで四頭筋全層が切除された。切除後の再建として、対側の遊離前外側大腿皮弁（以下ALT）が使用された。採取されたALTの大腿筋膜～腸脛靭帯を、遠位は膝蓋骨（骨孔を通し膝蓋靭帯に縫着）、近位は大腿直筋・中間広筋・外側広筋の腱成分と縫合した。内側広筋部は血管吻合部であったため縫合しなかった。術後4週間は膝伸展位で大腿～下腿までの外固定とした。　術直後はベッド上にて、患肢伸展位固定であり、この時点での筋力は徒手筋力検査（以下MMT）にて左大腿四頭筋0レベルで、筋収縮は認めなかった。術後4週にて患肢半荷重、関節可動域練習が許可され、左大腿四頭筋筋力はMMT2レベル、Extension Lag（以下Lag）-15°であった。関節可動域（以下ROM）は膝関節屈曲40°、伸展0°で、両松葉杖歩行可能ではあったが、「膝折れしそうで怖い」などの発言がみられた。【介入内容と結果】大腿四頭筋遠位部の全切除ののち、大腿筋膜～腸脛靭帯による再建が行われたが、遊離皮弁の為、術後は外固定による伸展位固定が必要な状態であった。この期間中も、①筋力維持・回復 ②癒着防止が必要の為、術直後は、残存している大腿四頭筋の筋力強化を目的にパテラセッティング（10回2セットを1日最低5回）、癒着予防目的にパテラモビライゼーションを行い、ベッドサイドでのセルフエクササイズも指導した。術後4週より伸展位固定解除され、膝屈曲可動域練習および端坐位での膝関節伸展運動も行い、膝関節伸展機能の再獲得を目指した。可動域練習は再建腱の伸張には十分注意して、屈曲角とLagを評価しつつ行った。　術後7週にて患肢全荷重が許可されたため、スクワットなど荷重位でのトレーニングと歩行練習を中心に行った。膝関節屈曲可動域練習開始後にLagは一時的に-30°まで増大したが、術後8週では-15°まで改善を認めた。左大腿四頭筋筋力はMMT2レベル、ROMは膝関節屈曲90°、伸展0°まで改善し、歩行は装具を使用せずに片松葉杖歩行可能であった。10ｍ歩行は11.95秒で、「安心して歩けるようになって嬉しい」などの発言もみられ、X+58日に自宅退院となった。【結論】　術後経過において、Lagが低下した原因は、術後の屈曲角度拡大に伴い再建腱の伸張が生じたためと考えられたが、関節可動域の内容を制限し、筋力トレーニングを中心に行うことでさらなる再建腱の伸張を予防することができたと考える。また、本症例はLagがあるためMMTでは2の判定となるが、屈曲位では徒手抵抗でMMT4相当の筋出力が可能となり、膝関節屈曲位での支持性が得られ、膝折れが予防出来たと考える。一方、膝関節軽度屈曲位から完全伸展では四頭筋の筋収縮が十分に得られなかったが、荷重位でのスクワット運動を取り入れることにより、ハムストリングスおよび膝関節伸展ロックによる制御が可能となり、膝関節軽度屈曲位から完全伸展位においても膝折れが予防出来たと考える。　これらの介入により、術式より膝折れが予想されたが、装具を使用せずに片松葉杖歩行自立に至ったと考える。　今回の結果より、広範切除施行後のリハビリテーションは、手術内容を理解し、残存機能に着目した適切な筋力トレーニングが有効であることが示唆された。【倫理的配慮，説明と同意】本研究は名古屋大学生命倫理審査委員会の承認を得た上で、ヘルシンキ宣言に基づき、患者に十分な説明を行い、書面にて同意を得て行った。

DOI： 10.14900/cjpt.46s1.h2-114_1

外反変形性膝関節症患者に対する人工膝関節全置換術前後の特徴について Reviewed

加古誠人, 栗谷彩, 髙木優衣, 森友洋, 寺井千晶, 神山卓史, 白井祐也, 平岩英樹, 濱田恭, 門野泉, 西田佳弘

理学療法学Supplement Vol. 46S1 ( 0 ) page： H2-71_1 - H2-71_1 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに】 変形性膝関節症（膝OA）は、関節変形や可動域制限、筋力低下、疼痛を主症状とし、膝OAに対する外科手術の一つに人工膝関節全置換術（TKA）があり、除痛、変形矯正を目的として広く行われている。膝OAの変形は、内反膝OAが90％以上を占め、外反膝OAの発症率は低いと言われている。そのため、TKAに関する解析は内反膝OAに関する報告が多く、外反膝OAに関する報告は非常に少ない。【目的】本研究の目的は、内反膝OAと外反膝OAのTKA前後の身体機能および術後経過の差を解析し、外反膝OAに対して今後理学療法に必要となる特徴を明らかにすることとした。【方法】 対象は、2015年9月から2017年11月までの期間に初回のTKAを施行した膝OA患者のうち、評価困難例や神経疾患などの合併症を有する例を除外した84例とした。評価項目は、年齢、性別、BMI、大腿骨脛骨角（FTA）、手術時間、出血量、在院日数を診療録より調査した。疼痛はVisual Analogue Scale（VAS）を用いた。両股関節・両膝関節可動域（ROM）、10m快適歩行速度を測定した。下肢筋力（股関節外転筋、膝関節伸展筋）は、ハンドヘルドダイナモメータ（μTas F-100、アニマ社製）を用いて測定した。 全体を内反群（FTA175°以上）、外反群（175°未満）の2群に分けて比較検討した。統計処理は、2群間の比較を対応のないt検定で行った。結果は、平均値±標準偏差で示し、有意水準は5%未満とした。【結果】 内反群70例（年齢72.1±7.8歳、女性55例）、外反群14例（年齢70.9±7.6歳、女性12例）であった。両群間の年齢、性別において差はなかった。FTAは内反群186.3±7.1°、外反群166.6±8.3°であった。術前の身体機能は、健側股関節屈曲・外転ROM、患側股関節外転筋力、両側膝関節伸展筋力において外反群が有意に低かった。術後の身体機能は、VASにおいて外反群が有意に高く、患側膝関節伸展筋力は外反群が有意に低かった。その他に、手術時間、在院日数それぞれ外反群が有意に長かった。【結論】 術前の結果より、内反膝OAに比べ、外反膝OAは股関節の可動域および筋力の低下が認められた。外反膝では股関節の変形や内転拘縮を伴う症例も散見され、これが一因と考えた。また、術後の結果から外反膝OAは、術後疼痛や患側膝関節伸展筋力低下がより強く認められ、手術時間が長くなっていることから、内反OAに比べより術式の影響を強く受ける可能性が示唆された。 外反膝OAのTKA前後の理学療法介入は、膝関節のみならず股関節機能や術式、疼痛など内反膝OAとの違いを理解して、注意深く慎重な介入が必要であると考える。【倫理的配慮，説明と同意】本研究は名古屋大学生命倫理審査委員会の承認（承認番号：2015-0516）を得た上で、ヘルシンキ宣言に基づき、患者に十分な説明を行い、書面にて同意を得て行った。

DOI： 10.14900/cjpt.46s1.h2-71_1

内反型変形性膝関節症患者におけるTUGに影響を及ぼす因子の検討 Reviewed

白井祐也, 加古誠人, 髙木優衣, 神山卓史, 濱田恭, 寺井千晶, 門野泉, 森友洋, 栗谷彩, 西田佳弘, 平岩秀樹

理学療法学Supplement Vol. 46S1 ( 0 ) page： H2-219_2 - H2-219_2 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに、目的】Timed up and go test（TUG）は，下肢筋力，動的バランス，歩行能力を統合した評価指標として使用されている。変形性膝関節症（膝OA）患者において，TUGは，起立，歩行，階段昇降といった日常生活動作と大きく関連する評価項目として重要と言われている。近年，膝OA患者におけるTUGに影響を及ぼす因子は膝関節の運動機能に限局した報告が多く見られ，他関節を含む下肢の運動機能全般や，変形の重症度，疼痛を含めた因子での検討は十分にされていない。そこで本研究は，膝OA患者におけるTUGに影響を及ぼす因子を下肢の運動機能，変形の重症度，疼痛の項目から検討することを目的とした。【方法】対象は2014年6月から2017年11月までに初回の人工膝関節置換術目的に入院した内反型膝OA患者のうち，神経疾患の既往のある者，測定困難な者を除外した37例（女性29例，男性8例，年齢70.8±8.1歳，身長154.7±7.7cm，体重63.3±10.4kg）とした。TUGは2回測定し，平均値を使用した。運動機能の評価項目は，股関節，膝関節，足関節の関節可動域（ROM）と股関節外転，膝関節伸展の等尺性の最大筋力とした。筋力測定は，ハンドヘルドダイナモメータ（μTas F-100，アニマ社製）を使用した。変形の重症度は大腿脛骨角（Femoro-tibial angle：FTA）を使用し，疼痛に関する評価は，疼痛の程度（Visual analogue scale：VAS），疼痛に対する破局的思考の程度（Pain Catastrophizing Scale：PCS）を使用した。評価項目は手術前日に測定した。統計処理は，TUGに対する各指標間の関連、FTAと疼痛の関連を正規性に応じてPearsonの相関係数またはSpearmanの順位相関係数を用いて行った。結果は平均値±標準偏差で示し，有意水準は5％とした。【結果】TUGの平均値は10.7±2.5秒であった。TUG値は両側股関節内旋ROM（患側：r=-0.35，p<0.05/健側：r=-0.36，p<0.05），患側股関節内転ROM（r=-0.33，p<0.05），健側股関節外転筋力（r=-0.39，p<0.05），両側膝関節伸展筋力（患側：r=-0.44，p<0.01/健側：r=-0.36，p<0.05）と有意な負の相関を示した。変形の重症度を示すFTAや疼痛に関する評価のVASやPCSとの相関は認められなかった。またFTA はVASやPCSとも相関を認めなかった。【結論（考察も含む）】今回の結果からTUGは，健側，患側ともに股関節，膝関節の運動機能との相関を認めた。進行期あるいは末期内反型膝OA患者では患側の膝関節だけでなく，健側を含めた両側下肢の運動機能がTUGに関与していることが明らかとなった。一方でTUGは変形の重症度や疼痛の評価項目と相関を認めなかった。過去の報告と同様に変形の重症度と疼痛も相関を認めなかった。このことから内反型膝OA患者において変形の重症度や疼痛は必ずしもTUGの制限因子とならず，TUGはROMや筋力といった運動機能をより反映した評価指標であることが示唆された。【倫理的配慮，説明と同意】 本研究は名古屋大学生命倫理審査の承認を得た上で，ヘルシンキ宣言に基づき，対象者に十分な説明を行い，書面にて同意を得て実施した（承認番号：2018-0081）。

DOI： 10.14900/cjpt.46s1.h2-219_2

変形性膝関節症患者の健康関連QOLに関連する因子の検討 Reviewed

寺井千晶, 加古誠人, 髙木優衣, 神山卓史, 白井祐也, 森友洋, 濱田恭, 平岩秀樹, 門野泉, 西田佳弘, 栗谷彩

理学療法学Supplement Vol. 46S1 ( 0 ) page： H2-25_1 - H2-25_1 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに、目的】変形性膝関節症（膝OA）は本邦において多くの罹患患者を有する骨関節疾患の1つであり，その主な症状は膝関節痛である。荷重関節である膝関節の疼痛は患者の移動能力を低下させ，日常生活活動を障害し，さらに生活の質（Quality of life；QOL）の低下を招くとされる。QOLのうち，健康に関わるものは健康関連QOL（Health related quality of life；HRQOL）とされ，HRQOLの評価指標としてはSF-36が一般的に用いられる。どのような因子が膝OA患者のHRQOLに関連するか明らかにすることは，理学療法介入を行う上で一助となると考える。本研究の目的は膝OA患者のHRQOLに関連する因子を明らかにすることである。【方法】対象は2016年4月から2018年4月の間に手術目的で当院整形外科へ入院した膝OA患者のうち，術前評価時に歩行可能かつ質問紙評価が可能であった62例（女性：48例，男性：14例，平均年齢69.7±9.3歳：平均±SD）とした。HRQOLの評価には日本語版SF-36を用い，身体的側面，精神的側面および役割/社会的側面の3つのQOLサマリースコアを算出した。また疼痛の程度の評価にはVisual analog scale（VAS）を用い，疼痛に対する破局的思考の評価指標であるPain Catastrophizing Scale（PCS）を用いて反すう，無力感，拡大視の3つの数値を算出した。身体機能評価項目は膝伸展筋力（ハンドヘルドダイナモメーターを用いて測定），膝伸展/屈曲可動域（ROM），10m歩行速度（快適歩行速度，最大歩行速度）とした。統計学的解析にはSPSSを用い，3つのサマリースコアと各項目のSpearmanの順位相関係数を算出した。なお，有意水準は5％とした。【結果】身体的側面のスコアはVAS（r=-.258，p=.043），PCS反すう（r=-.255，p=.048），PCS無力感（r=-.282，p=.028），快適歩行速度（r=.371，p=.003），患側膝屈曲ROM（r=.387，p=.002）と有意な相関を認めた。精神的側面のスコアはVAS（r=-.424，p=.001），PCS反すう（r=-.370，p=.003），PCS無力感（r=-.346，r=.006），PCS拡大視（p=-.355，p=.005）と有意な相関を認めた。役割/社会的側面のスコアはPCS無力感（r=-.305，p=.017），PCS拡大視（r=-.345，p=.006），快適歩行速度（r=.359，p=.004），最大歩行速度（r=.343，p=.009）と有意な相関を認めた。【結論（考察も含む）】各サマリースコアにおいて，疼痛に関連する因子であるVASやPCSが有意な相関を認めることが明らかとなった。また身体機能では歩行速度が2つのサマリースコアにおいて有意な相関を認め，膝OA患者のHRQOLには疼痛や歩行速度が関連することが示唆された。したがって，手術を要するような進行期・末期膝OA患者に対し疼痛や歩行速度の改善を目指す理学療法介入を行うことは患者のHRQOL改善につながる可能性があると考える。【倫理的配慮，説明と同意】本研究は当院生命倫理審査委員会の承認を得た上で，ヘルシンキ宣言に基づき，患者に十分な説明を行い書面にて同意を得て実施した（承認番号：2015-0516）。

DOI： 10.14900/cjpt.46s1.h2-25_1

クリーゼを発症した抗LRP4抗体陽性重症筋無力症患者に対し運動負荷量に留意したリハビリテーションを施行した症例 Reviewed

森貴史, 柴田篤志, 西田佳弘, 熱田直樹, 門野泉, 森友洋, 永谷元基, 勝野雅央

理学療法学Supplement Vol. 46S1 ( 0 ) page： E-127_2 - E-127_2 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに・目的】 重症筋無力症（MG）は、神経筋接合部の刺激伝達が障害されて生じる疾患であり、手術ストレスや運動過負荷を誘因に、クリーゼと呼称される呼吸・球麻痺症状の増悪、全身性の筋力低下を来すことがある。クリーゼ発症後はリハビリテーション（リハ）により過用症候群を引き起こし、症状を再燃させるリスクがあるため、早期から積極的なリハは行われないことが多い。しかし、過度の安静によりディコンディショニングが惹起される可能性があるため、早期予防が重要となる。一方で、クリーゼ発症後の運動負荷量の設定を判断する指標は乏しい。 MG患者に対し運動療法の介入を推奨する報告（Nils G, Jan V 2015）はあるが、運動負荷量の詳細は不明である。今回、クリーゼを来し、ICUに入室した抗LRP4抗体陽性MG患者に対し、運動負荷量の設定に留意したリハを実施したため、ICU退室後のリハに着目して報告する。【方法】 対象は筋力低下、呼吸苦の精査目的に入院した60歳代男性。入院3日後にリハ開始となった。入院時のADLは自立されていたが、入院4日後に呼吸苦増悪し、人工呼吸器管理のためICU入室となった。入室後、MGのクリーゼと診断され、ICUにてステロイドパルス（mPSL）3日間、免疫グロブリン大量療法（IVIg）5日間実施されたが、奏功乏しく、血漿交換療法が加療された。ICU入室後より、コンディショニングを中心にリハを再開した。入院26日後にICU退室となったが、入院34日後にクリーゼ再燃し、ICU再入室した。再入室後はIVIgを5日間施行し、免疫抑制剤が併用された。入院55日後にICU退室となり、併存疾患のホジキンリンパ腫に対する化学療法が開始された。入院84日後、症状の改善に伴い人工呼吸器離脱となった。リハでは、ADL練習や自動運動を開始した。運動負荷量は疲労感、呼吸苦を修正Borg4以下で設定し、負荷量を調整した。その際、呼吸数の著しい増加やSpO2の低下の有無を監視した。評価は、筋力測定を1週間毎に行い、筋力低下、筋疲労の有無を確認しながら運動負荷量を調整した。入院93日後よりリハにて歩行を開始し、同時期よりリハ室でエルゴメーター、機器での12-15RMの運動を開始した。入院157日後にADL自立となり自宅退院となった。なお、今回のリハにより、筋力低下や呼吸苦などの有害事象は発生しなかった。【結果】（入院55/97/139/153日後）※ICU退室後より評価 ADL（Barthel Index）は0/85/100/100 点、MG-ADLスケールは22/12/5/2点、握力は左右平均9.5/20.3/32.8/33.2 kgf、膝伸展筋力は左右平均0.0/16.5/20.8/24.7 kgf、6MWDは0/240/430/459 mであった。【考察】 今回、治療と並行したリハの実施により退院時にADLは自立し、筋力、運動耐容能は改善した。本疾患において、ICU退室後に化学療法と並行して運動時の疲労感と筋力の変動を指標に段階的に負荷量を調整したリハを行ったことで、クリーゼを来したMGのディコンディショニングの予防に寄与した可能性がある。【倫理的配慮，説明と同意】本学生命倫理委員会の承認を得た上で、本人の同意を得て作成した（承認番号：2018-0019）。

DOI： 10.14900/cjpt.46s1.e-127_2

Early radiographic risk factors for rigid relapse in idiopathic clubfoot treated with the Ponseti method. Reviewed

画像診断と病理骨芽細胞腫 Reviewed

駒田智大, 長縄慎二, 岩野信吾, 新井英介, 西田佳弘, 下山芳江

画像診断 Vol. 39 ( 1 ) page： 4 - 5 2018.12

Mishima K, Kitoh H, Matsushita M, Sugiura H, Hasegawa S, Kitamura A, Nishida Y, Ishiguro N

Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons Vol. 24 ( 6 ) page： 509 - 513 2018.12

Post-operative regression of retro-odontoid pseudotumors treated with and without fusion. Reviewed

Kobayashi K, Imagama S, Ando K, Nishida Y, Ishiguro N

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society Vol. 27 ( 12 ) page： 3105 - 3112 2018.12

Feasibility and effects of a self-assembling peptide as a scaffold in bone healing: An in vivo study in rabbit lumbar posterolateral fusion and tibial intramedullary models Reviewed Open Access

Ando, K; Imagama, S; Kobayashi, K; Ito, K; Tsushima, M; Morozumi, M; Tanaka, S; Machino, M; Ota, K; Nishida, K; Nishida, Y; Ishiguro, N

JOURNAL OF ORTHOPAEDIC RESEARCH Vol. 36 ( 12 ) page： 3285 - 3293 2018.12

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

Spinal fusion and bone defects after injuries, removal of bone tumors, and infections require repair by implantation. In this study, we show self-assembling peptide (SPG-178) hydrogel-induced bone healing in vivo. Posterolateral lumbar fusion and tibial intramedullary models of rabbits were prepared. In the tibia model, micro-CT analysis revealed a significantly higher degree of newly formed bone matrix in the SPG-178 group compared to the other groups. SEM/3D micrographs showed that the cavity filled with SPG-178 had collagen fibers attached to host bone. After 28 days, samples from the SPG-178 group showed significant repair of the defect. In the posterolateral lumbar fusion models, micro-CT showed a tendency for a higher degree of newly formed bone matrix in the SPG-178 group compared to the β-TCP and bone chips only groups. Von Kossa staining showed marked new bone formation attached to the lamina that was most prominent at the implanted SPG-178 composite margin. SPG-178 is a material that is likely to be used in clinical applications because it has several benefits. These include its favorable bone conduction properties, its ability to act as a support for various cells and growth factors, its lack of infection risk compared with materials of animal origin such as ECM, and the ease with which it can be used to fill defects with complex shapes and be combined with a wide range of other materials. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3285–3293, 2018.

DOI： 10.1002/jor.24109

Atypical vertebral column fracture at the middle of fused area after instrumented posterior decompression and fusion surgery for beak type thoracic ossification of the posterior longitudinal ligament Reviewed

Postoperative Complications Associated With Spine Surgery in Patients Older Than 90 Years: A Multicenter Retrospective Study Reviewed Open Access

Kobayashi, K; Imagama, S; Sato, K; Kato, F; Kanemura, T; Yoshihara, H; Sakai, Y; Shinjo, R; Hachiya, Y; Osawa, Y; Matsubara, Y; Ando, K; Nishida, Y; Ishiguro, N

GLOBAL SPINE JOURNAL Vol. 8 ( 8 ) page： 887 - 891 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Global Spine Journal

Study Design: A review of a prospective database. Objectives: Surgery for elderly patients is increasing yearly due to aging of society and the desire for higher quality of life. The goal of the study was to examine perioperative complications in spine surgery in such patients. Methods: A multicenter study of surgical details and perioperative complications was performed in 35 patients aged older than 90 years who underwent spinal surgery, based on a review of a prospective database. The frequency and severity of complications were assessed, and the effects of patient-specific and surgical factors were examined. Major complications were defined as those that were life threatening, required reoperation in the perioperative period or left a permanent injury. Ambulatory function before and after surgery was also analyzed. Results: Perioperative complications occurred in 19 of the 35 cases (54%), and included 11 cases of postoperative delirium, most of which occurred after cervical spine surgery. There were 8 major complications (23%), including cerebral infarction (n = 3), coronary heart disease (n = 3), pulmonary embolism (n = 1), and angina (n = 1). Preoperative motor deficit, operative time, estimated blood loss, and instrumented fusion were significantly associated with major complications. An improved postoperative ambulatory status occurred in 61% of cases, with no change in 33%, and worsening in 2 cases (6%). Conclusions: Timing of surgery before paralysis progression and reduced surgical invasiveness are important considerations in treatment of the very elderly. Improved outcomes can be obtained with better management of spine surgery for patients aged 90 years or older.

DOI： 10.1177/2192568218767430

Serum cystatin C level is associated with locomotive syndrome risk and can be an early predictor in community-living people: The Yakumo study. Reviewed Open Access

Tanaka S, Ando K, Kobayashi K, Hida T, Ito K, Tsushima M, Morozumi M, Machino M, Ota K, Seki T, Suzuki K, Nishida Y, Ishiguro N, Hasegawa Y, Imagama S

Modern rheumatology Vol. 28 ( 6 ) page： 1035 - 1040 2018.11

Imagama, S; Ando, K; Kobayashi, K; Hida, T; Ito, K; Tsushima, M; Ishikawa, Y; Matsumoto, A; Nishida, Y; Ishiguro, N

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 23 ( 6 ) page： 1100 - 1104 2018.11

A randomized phase III study of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group study JCOG1610 Reviewed

Urakawa, H; Mizusawa, J; Tanaka, K; Eba, J; Hiraga, H; Hosaka, M; Kawai, A; Nakatani, F; Kobayashi, E; Nishida, Y; Okamoto, T; Matsunobu, T; Iwamoto, Y; Fukuda, H; Ozaki, T

ANNALS OF ONCOLOGY Vol. 29 2018.10

Outpatient chemotherapy for patients with unresectable or metastatic bone sarcomas Reviewed

Urakawa, H; Nishida, Y; Mitsuma, A; Maeda, O; Sugishita, M; Shimokata, T; Mizutani, T; Arai, E; Ikuta, K; Hamada, S; Ota, T; Ishiguro, N; Ando, Y

ANNALS OF ONCOLOGY Vol. 29 2018.10

A case report; Surgery and rehabilitation for spinal canal stenosis in achondroplasia Reviewed

HISHIDA Aika

The Central Japan Journal of Orthopaedic Surgery & Traumatology Vol. 61 ( 5 ) page： 963 - 964 2018.9

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study Reviewed Open Access

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

WORLD JOURNAL OF SURGICAL ONCOLOGY Vol. 16 ( 1 ) page： 160 2018.8

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

Background: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. Methods: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Results: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p=0.034 and p=0.022, respectively). In patients treated with perioperative desnosumab, 120mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p<0.001). Conclusion: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

DOI： 10.1186/s12957-018-1459-6

Epidemiological trends in spine surgery over 10 years in a multicenter database Reviewed

Kobayashi, K; Ando, K; Nishida, Y; Ishiguro, N; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 27 ( 8 ) page： 1698 - 1703 2018.8

Reoperation within 2 years after lumbar interbody fusion: a multicenter study Reviewed

Kobayashi, K; Ando, K; Kato, F; Kanemura, T; Sato, K; Hachiya, Y; Matsubara, Y; Kamiya, M; Sakai, Y; Yagi, H; Shinjo, R; Nishida, Y; Ishiguro, N; Imagama, S

EUROPEAN SPINE JOURNAL Vol. 27 ( 8 ) page： 1972 - 1980 2018.8

Effect of postoperative doxorubicin administration on ischemic wound healing Reviewed Open Access

Morishita, T; Toriyama, K; Takanari, K; Yagi, S; Ebisawa, K; Hishida, M; Narita, Y; Osaga, S; Nishida, Y; Kamei, Y

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 80 ( 3 ) page： 357 - 366 2018.8

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

Some patients undergo postoperative chemotherapy despite showing impaired wound healing after a major surgery. We speculated that postoperative chemotherapy further delays wound healing in these patients. This study aimed to compare the effects of doxorubicin (DXR) in ischemic skin flap and normal incisional wound models after surgery. A 2-cm incisional wound was made in group 1 rats, and saline was injected intravenously, following surgery on the same day. Incisional wound was made in group 2-5 rats, and 8 mg/kg DXR was injected intravenously, following surgery on the same day and after 7, 14, and 21 days respectively. H-shaped double flaps were made in group 6 rats, and saline was injected intravenously, following surgery on the same day. Flaps were made in group 7-10 rats, and 8 mg/kg DXR was injected intravenously, following surgery on the same day and after 7, 14, and 21 days respectively. On days 7, 14, 21, and 28 after surgery, the suture wounds were removed, tensile wound strengths were measured, and tissue samples were collected for histopathological evaluation. The tensile strength was significantly lower in the DXR-treated groups than in the control groups for both ischemic skin flaps and incision wounds. Additionally, the cross effect between DXR and ischemia was not significant. On pathological examination, DXR showed atrophic skin changes and degeneration of skin appendages on days 14-21 after the surgery in both the models. DXR decreased the wound tensile strength and caused an atrophic change in the ischemic wound.

DOI： 10.18999/nagjms.80.3.357

Surgical intervention for a pediatric isolated intramedullary spinal aneurysm. Reviewed

Morozumi M, Imagama S, Ando K, Kobayashi K, Hida T, Ito K, Tsushima M, Matsumoto A, Tanaka S, Machino M, Ota K, Nishida Y, Ishiguro N

Eur Spine J. Vol. 27 ( Suppl 3 ) page： 342 - 346 2018.7

Surgical outcomes of spinal cord and cauda equina ependymoma: Postoperative motor status and recurrence for each WHO grade in a multicenter study. Reviewed Open Access

Kobayashi K, Ando K, Kato F, Kanemura T, Sato K, Kamiya M, Nishida Y, Ishiguro N, Imagama S

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association Vol. 23 ( 4 ) page： 614 - 621 2018.7

The Feature of Clinical and Radiographic Outcomes in Elderly Patients with Cervical Spondylotic Myelopathy: A Prospective Cohort Study on 1025 Patients. Reviewed

Machino M, Imagama S, Ando K, Kobayashi K, Ito K, Tsushima M, Matsumoto A, Morozumi M, Tanaka S, Ito K, Kato F, Nishida Y, Ishiguro N

Spine Vol. 43 ( 12 ) page： 817 - 823 2018.6

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

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

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

Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma. Reviewed Open Access

Hamada S, Nishida Y, Zhuo L, Shinomura T, Ikuta K, Arai E, Koike H, Kimata K, Ushida T, Ishiguro N

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

Analysis of the Infiltrative Features of Chordoma: The Relationship Between Micro-Skip Metastasis and Postoperative Outcomes Reviewed

Akiyama Toru, Ogura Koichi, Gokita Tabu, Tsukushi Satoshi, Iwata Shintaro, Nakamura Tomoki, Matsumine Akihiko, Yonemoto Tsukasa, Nishida Yoshihiro, Saita Kazuo, Kawai Akira, Matsumoto Seiichi, Yamaguchi Takehiko

ANNALS OF SURGICAL ONCOLOGY Vol. 25 ( 4 ) page： 912 - 919 2018.4

Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification Reviewed

Yamashita Kyoko, Kohashi Kenichi, Yamada Yuichi, Ishii Takeaki, Nishida Yoshihiro, Urakawa Hiroshi, Ito Ichiro, Takahashi Mitsuru, Inoue Takeshi, Ito Masafumi, Ohara Yuuki, Oda Yoshinao, Toyokuni Shinya

HISTOPATHOLOGY Vol. 72 ( 5 ) page： 729 - 738 2018.4

Single metastasis of myxoid liposarcoma from the thigh to thyroid gland: a case report Reviewed Open Access

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

WORLD JOURNAL OF SURGICAL ONCOLOGY Vol. 16 ( 1 ) page： 71 2018.3

Image Diagnostic Classification of Magnetic Resonance T2 Increased Signal Intensity in Cervical Spondylotic Myelopathy: Clinical Evaluation Using Quantitative and Objective Assessment. Reviewed

Machino M, Imagama S, Ando K, Kobayashi K, Ito K, Tsushima M, Matsumoto A, Morozumi M, Tanaka S, Ito K, Kato F, Nishida Y, Ishiguro N

Spine Vol. 43 ( 6 ) page： 420 - 426 2018.3

Sarcopenia and physical function are associated with inflammation and arteriosclerosis in community-dwelling people: The Yakumo study Reviewed

Hida Tetsuro, Imagama Shiro, Ando Kei, Kobayashi Kazuyoshi, Muramoto Akio, Ito Kenyu, Ishikawa Yoshimoto, Tsushima Mikito, Nishida Yoshihiro, Ishiguro Naoki, Hasegawa Yukiharu

Modern rheumatology Vol. 28 ( 2 ) page： 345 - 350 2018.3

Effects of a self-assembling peptide as a scaffold on bone formation in a defect Reviewed Open Access

Ando Kei, Imagama Shiro, Kobayashi Kazuyoshi, Ito Kenyu, Tsushima Mikito, Morozumi Masayoshi, Tanaka Satoshi, Machino Masaaki, Ota Kyotaro, Nishida Koji, Nishida Yoshihiro, Ishiguro Naoki

PLOS ONE Vol. 13 ( 1 ) page： e0190833 2018.1

Efficacy of Conical Laminoplasty After Thoracic Laminectomy. Reviewed

Kobayashi K, Imagama S, Ando K, Nishida Y, Ishiguro N

Clinical spine surgery Vol. 31 ( 4 ) page： 156 - 161 2018

Self-efficacy is an independent predictor for postoperative six-minute walk distance after elective open repair of abdominal aortic aneurysm Reviewed Open Access

Hayashi Kazuhiro, Kobayashi Kiyonori, Shimizu Miho, Tsuchikawa Yohei, Kodama Akio, Komori Kimihiro, Nishida Yoshihiro

Disability and rehabilitation Vol. 40 ( 10 ) page： 1114 - 1118 2018

Post-operative delayed ambulation after thymectomy is associated withpre-operative six-minute walk distance. Reviewed Open Access

Hayashi K, Fukumoto K, Yokoi K, Nagaya M, Inoue T, Ito S, Nakajima H, Hattori K, Kadono I, Nishida Y

Disability and rehabilitation Vol. 40 ( 16 ) page： 1900 - 1905 2018

Impact of variation in physical activity after total joint replacement Reviewed Open Access

Hayashi, K; Kako, M; Suzuki, K; Takagi, Y; Terai, C; Yasuda, S; Kadono, I; Seki, T; Hiraiwa, H; Ushida, T; Nishida, Y

JOURNAL OF PAIN RESEARCH Vol. 11 page： 2399 - 2406 2018

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

Purpose: Patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) often develop postoperative pain. Exercise approaches are recommended postoperatively; however, the impact of excessive variation in physical activity is unclear. The purpose of the present preliminary study was to investigate the impact of excessive variation in physical activity using the accelerometer in the early period after TKA or THA. Patients and methods: Seventy-two patients were enrolled in the study. Forty patients underwent initial TKA, and 32 initial THA. Physical activity was measured for 8 days from postoperative day 3 to 10. Patients with substantial correlation between physical activity and postoperative day were classified as the “good-pacing” group. Patients with no correlation between them were classified as the “poor-pacing” group. They were also evaluated using a pain visual analog scale (VAS), pain catastrophizing scale, and hospital anxiety and depression scale. Results: The average age was 68 years, and 59 patients (82%) were women. The average maximum number of steps per day was 2,181. There were 45 patients with good pacing and 27 with poor pacing. The poor-pacing group showed significantly lower maximum number of steps per day, higher postoperative average VAS score, higher postoperative worst VAS score, and longer duration of postoperative hospital stay than the good-pacing group. Conclusion: Patients with excessive variation in physical activity showed severe postoperative pain and prolonged postoperative hospital stay. The postoperative variation in physical activity could be an outcome for improvement in patients after lower-limb arthroplasty.

DOI： 10.2147/JPR.S178853

Posterior fusion of the occipital axis in children with upper cervical disorder using both C2 pedicle and laminar screws (C2 hybrid screws) Reviewed Open Access

Ito K., Imagama S., Ando K., Kobayashi K., Tsushima M., Matsumoto A., Morozumi M., Tanaka S., Machino M., Nishida Y., Ishiguro N.

Spine Surgery and Related Research Vol. 2 ( 1 ) page： 82 - 85 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：Spine Surgery and Related Research

Introduction: An occipital-cervical surgery for children is challenging for surgeons because of the immature bone quality, extensive anatomical variability, and small osseous structures. Furthermore, occipital-C2 fusion in children results in great stress on the C2 screws. We report a technique that uses both C2 pedicle and bilateral lateral mass screws (C2 hybrid screws) in children with an upper cervical disorder to preserve motion segment and secure strength in those who require occipital-cervical fusion. Case Report: Case 1 was that of a 5-year-old girl with Down syndrome who had atlantoaxial dislocation and os odontoideum. Owing to the C1 hypoplasia, the posterior arch was fractured by the C1 lateral mass screw. Therefore, O-C2 fusion was performed. C2 bilateral lamina screws were added along with the C2 bilateral pedicle screws for reinforcement. Case 2 was that of an 8-year-old boy who presented with torticollis and neck pain. The patient was diagnosed as having atlantoaxial rotatory fixation. The right vertebral artery was obstructed, and the left vertebral artery was dominant. The C1 posterior arch was bifid and assimilated with the occipital bone. C2 bilateral lamina screws were added with the right C2 pedicle screw for reinforcement. Both cases attained bone union after O-C2 fusion surgery using hybrid screws. Conclusions: The use of C2 hybrid screws with both C2 pedicle and bilateral lateral mass screws can preserve mobile segments in the fusion area in young children who require occipital-cervical fixation.

DOI： 10.22603/ssrr.2016-0018

Independent association of joint space narrowing, cyst formation and health-related quality of life of patients with hip osteoarthritis in Japan Reviewed

Analysis of falls that caused serious events in hospitalized patients Reviewed

Kobayashi Kazuyoshi, Imagama Shiro, Ando Kei, Inagaki Yuko, Suzuki Yusuke, Nishida Yoshihiro, Nagao Yoshimasa, Ishiguro Naoki

GERIATRICS & GERONTOLOGY INTERNATIONAL Vol. 17 ( 12 ) page： 2403 - 2406 2017.12

Takegami Yasuhiko, Seki Taisuke, Higuchi Yoshitoshi, Komatsu Daigo, Nishida Yoshihiro, Ishiguro Naoki

JOURNAL OF ORTHOPAEDIC SCIENCE Vol. 22 ( 6 ) page： 1096 - 1101 2017.11

Preoperative Six-Minute Walk Distance and Desaturation in Patients with Malignant Pleural Mesothelioma Reviewed

Nagaya, M; Ito, S; Fukui, T; Inoue, T; Mizuno, Y; Kawaguchi, K; Nakamura, S; Nishida, Y; Hasegawa, Y; Yokoi, K

JOURNAL OF THORACIC ONCOLOGY Vol. 12 ( 11 ) page： S2308 - S2308 2017.11

Clinical and Radiographical Differences Between Thoracic Idiopathic Spinal Cord Herniation and Spinal Arachnoid Cyst Reviewed

Nakashima Hiroaki, Imagama Shiro, Yagi Hideki, Kato Fumihiko, Kanemura Tokumi, Sato Koji, Kawakami Noriaki, Kamiya Mitsuhiro, Yoshihara Hisatake, Ito Kenyu, Matsuyama Yukihiro, Nishida Yoshihiro, Ishiguro Naoki

SPINE Vol. 42 ( 16 ) page： E963 - E968 2017.8

The poor quality and reliability of information on periacetabular osteotomy on the internet in Japan Reviewed Open Access

Takegami Yasuhiko, Seki Taisuke, Amano Takafumi, Higuchi Yoshitoshi, Komatsu Daigo, Nishida Yoshihiro, Ishiguro Naoki

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 79 ( 3 ) page： 375 - 385 2017.8

Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model Reviewed Open Access

Higuchi, Y; Nishida, Y; Kozawa, E; Zhuo, LS; Arai, E; Hamada, S; Morita, D; Ikuta, K; Kimata, K; Ushida, T; Ishiguro, N

SCIENTIFIC REPORTS Vol. 7 ( 1 ) page： 7028 2017.8

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

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

DOI： 10.1038/s41598-017-07376-5

Heat-stimuli-enhanced osteogenesis using clinically available biomaterials Reviewed Open Access

Ota, T; Nishida, Y; Ikuta, K; Kato, R; Kozawa, E; Hamada, S; Sakai, T; Ishiguro, N

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

Language：English Publishing type：Research paper (scientific journal) Publisher：Plos One

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

DOI： 10.1371/journal.pone.0181404

Collaboration with an infection control team for patients with infection after spine surgery Reviewed

Kobayashi, K; Imagama, S; Kato, D; Ando, K; Hida, T; Ito, K; Tsushima, M; Matsumoto, A; Morozumi, M; Tanaka, S; Yagi, T; Nishida, Y; Ishiguro, N

AMERICAN JOURNAL OF INFECTION CONTROL Vol. 45 ( 7 ) page： 767 - 770 2017.7

Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Infection Control

Background The risk of infection, including surgical site infection (SSI), after spine surgery has increased due to aging and more immunocompromised hosts. An infection control team (ICT) is responsible for management of health care-associated infections at our institution. Methods The study subjects were 40 patients (18 men and 22 women with an average age of 54 years) referred to the ICT after spine surgery since 2010. Pathogenic bacteria and treatment in these cases were reviewed. Results Collaboration with the ICT involved guidance on use of antibiotics for infection in 30 patients (16 SSI and 14 non-SSI) and a search for the infection focus for fever of unknown origin in 10 patients (7 patients were found to have urinary tract infections and 2 patients were found to have pneumonia). The detection rate of causative bacteria in ICT consultation was 88% (35 out of 40 patients). SSI patients with instrumentation involved had a significantly higher rate of methicillin-resistant Staphylococcus aureus infection compared with those without instrumentation (42% vs 13%; P <.05). Discussion All cases of SSI with instrumentation involved were cured by ICT support without removal of instrumentation. Early assistance from the ICT was important for prevention of worsening of methicillin-resistant S aureus infection. Conclusions Collaboration with the ICT was helpful for detection of pathogenic bacteria and allowed appropriate use of antibiotics at an early stage.

DOI： 10.1016/j.ajic.2017.01.013

Aggressive osteoblastoma of the cervical spine involving the canal and vertebral artery: a case report Reviewed

Characteristics of Residual Symptoms After Laminoplasty in Diabetic Patients With Cervical Spondylotic Myelopathy Reviewed Open Access

Machino Masaaki, Imagama Shiro, Ando Kei, Kobayashi Kazuyoshi, Hida Tetsuro, Ito Kenyu, Tsushima Mikito, Matsumoto Akiyuki, Tanaka Satoshi, Morozumi Masayoshi, Ito Keigo, Kato Fumihiko, Nishida Yoshihiro, Ishiguro Naoki

SPINE Vol. 42 ( 12 ) page： E708 - E715 2017.6

Analysis of Factors for Predicting Survival in Soft-tissue Sarcoma with Metastatic Disease at Initial Presentation. Reviewed Open Access

Nakamura T, Katagiri H, Shido Y, Hamada S, Yamada K, Nagano A, Yamada S, Tsukushi S, Ishimura D, Matsumine A, Sudo A, Nishida Y.

Anticancer Res. Vol. 37 ( 6 ) page： 3137 - 3141 2017.6

Ando, K; Imagama, S; Kobayashi, K; Nishida, Y; Ishiguro, N

EUROPEAN SPINE JOURNAL Vol. 26 ( 1 ) page： S111 - S116 2017.5

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

Objective We present such a case of aggressive osteoblastoma of cervical spine. We describe its complicated clinical progression, hoping to shed light on the surgical strategy of this complex tumor. Methods We present such a case of aggressive osteoblastoma involving the C6–7 vertebrae. A 25-year-old man was diagnosed as aggressive osteoblastoma of the cervical spine. The lesion encroached upon the radicular foramina and was located adjacent to the canal of the vertebral artery. Preoperative embolization was performed to reduce intraoperative bleeding and to prevent intraoperative injury of the vertebral artery. Results A pathologic examination showed osteoblasts suggestive of osteoblastoma. At 2-year follow-up, bony union was achieved, and there was no evidence of recurrence on a CT scan. Conclusion En bloc total resection for highly vascular osteoblastoma is ideal, but this case shows that piecemeal total resection following preoperative embolization is a surgical option for highly expansive osteoblastoma.

DOI： 10.1007/s00586-016-4904-7

Associations among pain catastrophizing, muscle strength, and physical performance after total knee and hip arthroplasty Reviewed Open Access

Hayashi K., Kako M., Suzuki K., Hattori K., Fukuyasu S., Sato K., Kadono I., Sakai T., Hasegawa Y., Nishida Y.

World Journal of Orthopedics Vol. 8 ( 4 ) page： 336 - 341 2017.4

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

AIM To investigate whether reductions in pain catastrophizing associated with physical performance in the early period after total knee arthroplasty (TKA) or total hip arthroplasty (THA). METHODS The study group of 46 participants underwent TKA or THA. The participants were evaluated within 7 d before the operation and at 14 d afterwards. Physical performance was measured by the Timed Up and Go (TUG) test, and 10-m gait time was measured at comfortable and maximum speeds. They rated their knee or hip pain using a visual analog scale (VAS) for daily life activities. Psychological characteristics were measured by the Pain Catastrophizing Scale (PCS). Physical characteristics were measured by isometric muscle strength of knee extensors and hip abductors on the operated side. The variables of percent changes between pre- and postoperation were calculated by dividing post-operation score by pre-operation score. RESULTS Postoperative VAS and PCS were better than preoperative for both TKA and THA. Postoperative physical performance and muscle strength were poorer than preoperative for both TKA and THA. The percent change in physical performance showed no correlation with preoperative variables. In TKA patients, the percent change of PCS showed correlation with percent change of TUG (P = 0.016), 10-m gait time at comfortable speeds (P = 0.003), and 10-m gait time at maximum speeds (P = 0.042). The percent change of muscle strength showed partial correlation with physical performances. The percent change of VAS showed no correlation with physical performances. On the other hand, in THA patients, the percent change of hip abductor strength showed correlation with percent change of TUG (P = 0.047), 10-m gait time at comfortable speeds (P = 0.001), and 10-m gait time at maximum speeds (P = 0.021). The percent change of knee extensor strength showed partial correlation with physical performances. The percent change of VAS and PCS showed no correlation with physical performances. CONCLUSION Changes in pain catastrophizing significantly associated with changes in physical performance in the early period after TKA. It contributes to future postoperative rehabilitation of arthroplasty.

DOI： 10.5312/wjo.v8.i4.336

Comparative Study of Surgical Treatment and Nonsurgical Follow Up for Thoracic Ossification of the Posterior Longitudinal Ligament: Radiological and Clinical Evaluation Reviewed

Ando, K; Imagama, S; Kobayashi, K; Hida, T; Ito, K; Tsushima, M; Ishikawa, Y; Matsumoto, A; Nishida, Y; Ishiguro, N

SPINE Vol. 42 ( 6 ) page： 407 - 410 2017.3

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

Study Design. A prospective clinical study of factors related to myelopathy deterioration caused by thoracic myelopathy because of ossification of the posterior longitudinal ligament (T-OPLL). Objective. The objective of the study was to investigate factors related to myelopathy deterioration caused by T-OPLL. Summary of Background Data. Detailed analyses of factors related to myelopathy deterioration caused by T-OPLL have not been reported. Methods. Twenty-two patients (group O) received observation therapy because of the absence of or mild myelopathy, which was defined as walking unaided or with support, and a Japanese Orthopedic Association (JOA) score above 7 points; and 24 patients (group S) were treated with posterior decompression and fusion with instrumentation. Age, sex, body mass index (BMI), presence of diabetes mellitus (DM), and JOA score were obtained for all patients. Radiologically, the T-OPLL level, number of T-OPLLs, canal diameter ratio (CDR), morphology, ossification of the ligamentum flavum (OLF), and cervical OPLL were examined on reconstructed CT, and the presence of hyperintense areas (HIAs) on T2-weighted sagittal MR images. Results. In total, the patients included 22 males and 24 females and had an age range from 18 to 80 years. Sex, DM, JOA score in each domain, OPLL location, OPLL number, CDR of OPLL, morphology, OLF, and cervical OPLL did not differ significantly between groups N and S. However, cases in group N had a significantly higher age, lower weight, lower BMI, lower discontinuous rate on sagittal CT, and a lower HIA rate on MRI. Postoperatively, discontinuous segments connected and became continuous across the disc space in all patients in group S without progression of OPLL thickness. Conclusion. Age, weight, BMI, discontinuity between rostral and caudal OPLL lesions, and occurrence of a high intensity area on MRI are likely to be associated with development of myelopathy.

DOI： 10.1097/BRS.0000000000001769

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

Ikuta, K; Ota, T; Zhuo, LS; Urakawa, H; Kozawa, E; Hamada, S; Kimata, K; Ishiguro, N; Nishida, Y

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

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

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

DOI： 10.1002/ijc.30460

Transcranial motor evoked potential waveform changes in corrective fusion for adolescent idiopathic scoliosis Reviewed

Kobayashi, K; Imagama, S; Ito, Z; Ando, K; Hida, T; Ito, K; Tsushima, M; Ishikawa, Y; Matsumoto, A; Nishida, Y; Ishiguro, N

JOURNAL OF NEUROSURGERY-PEDIATRICS Vol. 19 ( 1 ) page： 108 - 115 2017.1

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

OBJECTIVE: Corrective surgery for spinal deformities can lead to neurological complications. Several reports have described spinal cord monitoring in surgery for spinal deformity, but only a few have included patients younger than 20 years with adolescent idiopathic scoliosis (AIS). The goal of this study was to evaluate the characteristics of cases with intraoperative transcranial motor evoked potential (Tc-MEP) waveform deterioration during posterior corrective fusion for AIS. METHODS: A prospective database was reviewed, comprising 68 patients with AIS who were treated with posterior corrective fusion in a prospective database. A total of 864 muscles in the lower extremities were chosen for monitoring, and acceptable baseline responses were obtained from 819 muscles (95%). Intraoperative Tc-MEP waveform deterioration was defined as a decrease in intraoperative amplitude of ≥ 70% of the control waveform. Age, Cobb angle, flexibility, operative time, estimated blood loss (EBL), intraoperative body temperature, blood pressure, number of levels fused, and correction rate were examined in patients with and without waveform deterioration. RESULTS: The patients (3 males and 65 females) had an average age of 14.4 years (range 11-19 years). The mean Cobb angles before and after surgery were 52.9° and 11.9°, respectively, giving a correction rate of 77.4%. Fourteen patients (20%) exhibited an intraoperative waveform change, and these occurred during incision (14%), after screw fixation (7%), during the rotation maneuver (64%), during placement of the second rod after the rotation maneuver (7%), and after intervertebral compression (7%). Most waveform changes recovered after decreased correction or rest. No patient had a motor deficit postoperatively. In multivariate analysis, EBL (OR 1.001, p = 0.085) and number of levels fused (OR 1.535, p = 0.045) were associated with waveform deterioration. CONCLUSIONS: Waveform deterioration commonly occurred during rotation maneuvers and more frequently in patients with a larger preoperative Cobb angle. The significant relationships of EBL and number of levels fused with waveform deterioration suggest that these surgical invasions may be involved in waveform deterioration.

DOI： 10.3171/2016.6.PEDS16141

Staged decrease of physical ability on the locomotive syndrome risk test is related to neuropathic pain, nociceptive pain, shoulder complaints, and quality of life in middle-aged and elderly people - The utility of the locomotive syndrome risk test Reviewed

Imagama Shiro, Hasegawa Yukiharu, Ando Kei, Kobayashi Kazuyoshi, Hida Tetsuro, Ito Kenyu, Tsushima Mikito, Nishida Yoshihiro, Ishiguro Naoki

MODERN RHEUMATOLOGY Vol. 27 ( 6 ) page： 1051 - 1056 2017

胸腺摘出術患者における術前6分間歩行距離は術後離床遅延を予測する Reviewed

永谷元基, 横井香平, 中島裕貴, 西田佳弘, 服部慶子, 門野泉, 井上貴行, 伊藤理, 林和寛, 福本紘一

理学療法学Supplement Vol. 2016 ( 0 ) page： 0784 2017

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに，目的】胸腺摘出術は，胸腺腫および重症筋無力症に対する治療法の一つである。胸腺腫患者の約1/3に重症筋無力症が合併するとされ，先行研究では重症筋無力症合併と胸腺摘出術後死亡率との関連が報告されている。胸部外科術後の理学療法においては，術後合併症の予防と身体機能の回復を主たる目的として術後早期から離床を行うことが推奨されている。術後の離床遅延は術後合併症や在院期間の延長につながることから，離床遅延に関連する要因を明らかにすることが求められている。そこで，本研究は胸腺摘出術患者において，術後離床遅延を予測する術前術中因子について検討した。【方法】2013年4月から2015年6月の期間に当院にて胸腺摘出術および周術期理学療法を施行した57例を対象とし，後方視的に検討した。術翌日に病棟歩行可能であった患者を早期離床群，歩行不可能であった患者を離床遅延群とした。評価指標は併存疾患，術前呼吸機能，術前6分間歩行距離（6MWD），手術時間，麻酔時間，出血量，術中水分バランス，術式，硬膜外麻酔使用の有無とした。各評価指標について，2群間をMann-Whitney U検定およびカイ二乗検定を用いて比較した。また，離床遅延の予測因子をロジスティック回帰分析で検討した。結果は平均値±標準偏差で示し，統計学的解析では有意水準を危険率0.05未満とした。【結果】対象の年齢は59±12歳，BMIは23.0±3.7 kg/m2であり，男性33例，女性24例であった。重症筋無力症を有していた患者は13例であった。早期離床群は31例，離床遅延群は26例であった。離床遅延群の病棟歩行開始日は，術後2日目が22例，術後3日目が4例であった。術後肺炎は離床遅延した1例のみに生じた。入院期間中には重症筋無力症クリーゼは発症しなかった。離床遅延群の術前6MWD（460±96 m）は，早期離床群（519±99 m）と比較して有意に低値を示した。重症筋無力症の有無の割合は両群間で差を認めず，その他の術前術中因子についても有意な差を認めなった。術前術中因子のうち，離床遅延の有無との関連が危険率0.2未満であった因子（高血圧，術前化学放射線療法，%肺活量，%1秒量，術前6MWD）を独立変数として抽出し，離床遅延の有無を従属変数として，ステップワイズ法を用いてロジスティック回帰分析を行った。ロジスティック回帰分析の結果，術前6MWDのみが離床遅延の独立した危険因子として抽出された。離床遅延と術前6MWDのReceiver Operating Characteristic曲線から算出された離床遅延のカットオフ値は498 mであった。【結論】胸腺摘出術後における離床遅延には術前6MWDが関連した。6MWDは術前評価指標の一つとして有用であり，術前6MWDが低値を示す患者においては術後に離床が遅延する可能性が推測されるため，術前後の介入方法を検討する必要があることが示唆された。

DOI： 10.14900/cjpt.2016.0784

生体肝移植術前後における筋力と6分間歩行距離の変化 Reviewed

水野陽太, 服部慶子, 伊藤理, 永谷元基, 西田佳弘, 大西康晴, 井上貴行, 倉田信彦, 長谷川好規, 小倉靖弘, 亀井秀弥

理学療法学Supplement Vol. 2016 ( 0 ) page： 0763 2017

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本理学療法士協会（現一般社団法人日本理学療法学会連合）

【はじめに，目的】末期肝障害患者の多くは，筋力や運動耐容能などの身体機能が低下している。身体機能の低下は肝移植術により数ヵ月から数年後に改善すると報告されているが，移植術後短期間の在院中にどのように変化するかは明らかではない。肝移植周術期における理学療法介入は，他の外科周術期と同様，術後合併症の予防や身体機能回復の促進を目的に行われており，筋力や運動耐容能の経過を把握することは重要である。肝移植による身体機能に関する報告の多くは脳死肝移植術を対象とした海外からのものであり，わが国で多く行われている生体肝移植術の報告は無い。そこで本研究は，生体肝移植術前後の身体機能の変化と，それらに関連する因子を検討することを目的とした。【方法】2014年4月から2015年12月までに当院で生体肝移植術を施行され，周術期理学療法が実施された成人21例を対象とした後方視的観察研究を行った。うち術前と術後4週目で評価が可能であった12例については，移植前後での身体機能を比較し，筋力の評価として握力ならびに等尺性膝伸展筋力，運動耐容能の評価として6分間歩行距離（6MWD）を測定した。術前後の評価指標についてはWilcoxonの符号順位検定を用いて比較し，各指標の相関はSpearmanの順位相関係数を用いて算出した。統計学的解析では有意水準を危険率0.05未満とした。【結果】評価群（n=12）と非評価群（n=9）では術前肝障害重症度の指標であるMELD scoreに有意差はみられなかった。評価群は全例が移植後自宅退院であったが，非評価群では2例が死亡退院であった。評価群の移植後の歩行開始は平均5.7日（2-17日），術後在院日数は平均54.2日（31-125日）であった。術前6MWDとMELD score（r=-0.646，P=0.023）ならびに呼吸機能の%VC（r=0.757，P=0.004），%FVC（r=0.776，P=0.003），%FEV1（r=0.734，P=0.007）には有意な相関がみられた。術前後の比較において6MWDに有意差はみられなかった（365.9±141.3 m vs. 341.1±139.7 m，P=0.182）が，握力（21.4±5.4 kgf vs. 17.3±5.9 kgf，P=0.015）と等尺性膝伸展筋力（19.1±5.4 kgf vs. 13.5±5.8 kgf，P=0.012）において有意な低下を認めた。術前MELD scoreと握力減少率（r=-0.604，P=0.038），等尺性膝伸展筋力減少率（r=-0.786，P=0.002）との間には有意な負の相関がみられた。【結論】生体肝移植術後4週の時点では，筋力は術前のレベルまで十分に回復しなかった。今後，移植後の筋力低下の軽減，早期回復を促す理学療法の確立が望まれる。

DOI： 10.14900/cjpt.2016.0763

四肢の骨・軟部肉腫 Reviewed

西田佳弘

日本小児血液・がん学会雑誌 Vol. 54 ( 3 ) page： 224 - 228 2017

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：日本小児血液・がん学会

日本整形外科学会の全国骨・軟部腫瘍登録データによるとAYA世代において発症数の多い肉腫として，骨原発では骨肉腫とEwing肉腫，軟部では横紋筋肉腫，滑膜肉腫，脂肪肉腫が挙げられる．その他にAYA世代に発症する特徴的な疾患として神経線維腫症1型に合併する悪性末梢神経鞘腫瘍（MPNST），良悪性の中間型であるデスモイド型線維腫症などがある．すべてが稀な疾患であり，各々の治療法が異なるために経験豊富な施設での治療が望まれる．横紋筋肉腫，デスモイド型線維腫症では診療ガイドラインを熟知していないために診療方針が施設ごとに大きく異なっていることが明らかとなった．骨・軟部肉腫の中でも，これまで通り診療レベルの均てん化および向上をめざすべき疾患と，診療の一層の集約化が必要である疾患があり，区別していく英断が必要であろう．四肢に好発する骨肉腫の治療では人工関節置換を必要とする場合が多く，治療後運動が制限されるとともに，腫瘍が治癒した後も人工関節の弛みや感染に対して複数回の手術が必要となる場合が多く，AYA世代および30歳以降も継続的な診療が必要となる．またMPNSTのように早期発見が遅れて治療成績が低下する疾患ではAYA世代のNF1患者への啓蒙が重要である．デスモイド型線維腫症では，腫瘍自体あるいは治療によって四肢の機能障害に悩まされるAYA世代患者が多く，多診療科による慎重な診療方針決定が重要となる．

DOI： 10.11412/jspho.54.224

Combination Treatment of Perioperative Rehabilitation and Psychoeducation Undergoing Thoracic Surgery Reviewed Open Access

Hayashi K., Inoue T., Nagaya M., Ito S., Nakajima H., Hattori K., Kadono I., Yokoi K., Nishida Y.

Case Reports in Medicine Vol. 2017 page： 4743952 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：Case Reports in Medicine

Postoperative pulmonary complications are a risk associated with thoracic surgery. However, there have been few reports on cases at high risk of postoperative complications. Cancer patients often have negative automatic thoughts about illness, and these negative automatic thoughts are associated with reduced health behavior and physical activity. This case series demonstrates the successful combination treatment of perioperative rehabilitation and psychoeducation for negative automatic thoughts in two cancer patients who underwent thoracic surgery. One patient underwent pneumonectomy with laryngeal recurrent nerve paralysis; the other patient, who had a history of recurrent hepatic encephalopathy and dialysis, underwent S6 segmentectomy. Both patients had negative automatic thoughts about cancer-related stress and postoperative pain. The physical therapists conducted a perioperative rehabilitation program in which the patients were educated to replace their maladaptive thoughts with more adaptive thoughts. After rehabilitation, the patients had improved adaptive thoughts, increased physical activity, and favorable recovery without pulmonary complications. This indicates that the combination treatment of perioperative rehabilitation and psychoeducation was useful in two thoracic cancer surgery patients. The psychoeducational approach should be expanded to perioperative rehabilitation of patients with cancer.

DOI： 10.1155/2017/4743952

病的骨折が大腿骨転移性骨腫瘍患者に与える影響の調査東海骨軟部腫瘍コンソーシアム多機関研究 Reviewed

酒井智久, 下山哲生, 中村知樹, 相羽久輝, 永野昭仁, 松峯昭彦, 紫藤洋二, 細野幸三, 小澤英史, 河南勝久, 西田佳弘, 今釜史郎

日本整形外科学会雑誌 Vol. 99 ( 6 ) page： S1457 - S1457 2025.6

軟部肉腫の肺転移に対して外科的切除およびラジオ波焼灼術を行った予後解析東海骨軟部腫瘍コンソーシアム研究 Reviewed

中村知樹, 小池宏, 筑紫聡, 小澤英史, 相羽久輝, 永野昭仁, 山田健志, 紫藤洋二, 河南勝久, 出淵雄哉, 西田佳弘

日本整形外科学会雑誌 Vol. 99 ( 2 ) page： S89 - S89 2025.3

Financial burden of surgical treatment for retroperitoneal sarcoma. Reviewed

Yokoyama Y, Sunagawa M, Kurimoto K, Sakai T, Nishida Y, Ebata T, Kodera Y.

Surg Today. Vol. 54 ( 10 ) page： 1201 - 1207 2024.10

The impact of goal-directed prehabilitation therapy on functional capacity in patients undergoing hepatobiliary and pancreatic surgery: A randomized clinical trial. Reviewed Open Access

Mizuno Y, Yokoyama Y, Nakajima H, Inoue T, Tanaka S, Nagaya M, Inokawa Y, Ando M, Nishida Y, Ebata T.

Surgery. Vol. 176 ( 2 ) page： 252 - 258 2024.8

Japanese orthopaedic association (JOA) clinical practice guidelines on the management of malignant bone tumors - Secondary publication. Reviewed

Tsuchiya K, Akisue T, Ehara S, Kawai A, Kawano H, Hiraga H, Hosono A, Hutani H, Morii T, Morioka H, Nishida Y, Oda Y, Ogose A, Shimose S, Yamaguchi T, Yamamoto T, Yoshida M.

J Orthop Sci. Vol. S0949-2658 ( 23 ) page： 00321 - 00324 2024.7

Preoperative Sarcopenia Severity and Clinical Outcomes after Total Hip Arthroplasty. Reviewed Open Access

Tanaka S, Kayamoto A, Terai C, Nojiri S, Fugane Y, Mori T, Nagaya M, Kako M, Iida H, Osawa Y, Takegami Y, Nishida Y.

Nutrients. Vol. 16 ( 13 ) page： 2085 - 2085 2024.6

膝関節周囲軟部肉腫術後の膝関節機能の検討 Reviewed

小池宏, 永野昭仁, 相羽久輝, 淺沼邦洋, 筑紫聡, 小澤英史, 河南勝久, 生田国大, 西田佳弘, 今釜史郎

日本整形外科学会雑誌 Vol. 98 ( 6 ) page： S1607 - S1607 2024.6

膝関節周囲軟部肉腫術後の膝関節機能の検討 Reviewed

小池宏, 永野昭仁, 相羽久輝, 淺沼邦洋, 筑紫聡, 小澤英史, 河南勝久, 生田国大, 西田佳弘, 今釜史郎

日本整形外科学会雑誌 Vol. 98 ( 6 ) page： S1607 - S1607 2024.6

補助人工心臓植込み後に高次脳機能障害を合併し、寛骨臼骨折受傷後、部分荷重歩行獲得に難渋した一例 Reviewed

堀勇斗, 寺井千晶, 府金幸紀, 森友洋, 山口英敏, 浅見雄太, 西田佳弘

国立大学リハビリテーション Vol. 45 page： 54 - 58 2024.4

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study. Reviewed Open Access

Tsuchikawa Y, Tanaka S, Kasugai D, Nakagawa R, Shimizu M, Inoue T, Nagaya M, Nasu T, Omote N, Higashi M, Yamamoto T, Jingushi N, Numaguchi A, Nishida Y.

Sci Rep. Vol. 14 ( 1 ) page： 5254 - 5254 2024.3

＜Editors' Choice＞ The relationship between preoperative foot alignment and postoperative outcomes in patients who underwent initial total knee arthroplasty. Reviewed Open Access

Hishida A, Hiraiwa H, Kadono I, Yamaguchi H, Okada T, Terai C, Kayamoto A, Nishida Y.

Nagoya J Med Sci. Vol. 86 ( 1 ) page： 91 - 103 2024.2

TGF-β signaling promotes desmoid tumor formation via CSRP2 upregulation. Reviewed

Li Y, Fujishita T, Mishiro-Sato E, Kojima Y, Niu Y, Taketo MM, Urano Y, Sakai T, Enomoto A, Nishida Y, Aoki M.

Cancer Sci. Vol. 115 ( 2 ) page： 401 - 411 2024.2

Sudo Y, Nishida Y, Nakashima H, Arai T, Takatsu T.

Medicina (Kaunas). Vol. 60 ( 1 ) page： 1 - 1 2023.12

Potential drug interactions between pazopanib and proton pump inhibitors/potassium-competitive acid blockers in patients with soft tissue sarcoma. Reviewed Open Access

Liang Y, Maeda O, Shimokata T, Yokota K, Koike H, Sakai T, Ikuta K, Urakawa H, Nishida Y, Akiyama M, Ando Y.

Int Cancer Conf J. Vol. 13 ( 1 ) page： 63 - 67 2023.11

Nakamura T, Sakai T, Tsukushi S, Kimura H, Wasa J, Hosono K, Izubuchi Y, Kozawa E, Nagano A, Asanuma K, Sudo A, Nishida Y.

In Vivo. Vol. 37 ( 6 ) page： 2642 - 2647 2023.11

The current management of clear cell sarcoma. Reviewed

Ikuta K, Nishida Y, Imagama S, Tanaka K, Ozaki T.

Jpn J Clin Oncol. Vol. 53 ( 10 ) page： 899 - 904 2023.10

Clinical investigation for the mechanisms of anaphylactic symptoms in osteoarthritis patients after diclofenac etalhyaluronate administration. Reviewed

Nishida Y, Yagami A, Takada S, Muramatsu D, Nobuoka Y, Okayama Y.

Mod Rheumatol. Vol. 20 2023.10

Efficacy of rehabilitation initiated in the early phase after simultaneous deceased donor liver and kidney transplantation: A case report. Reviewed

Tanaka S, Mizuno Y, Nojiri S, Futamura D, Nagaya M, Nishida Y, Sano Y, Ishida S, Kato M, Kurata N, Jobara K, Fujimoto Y, Ogura Y.

Medicine (Baltimore). Vol. 102 ( 38 ) page： e35324 - e35324 2023.9

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study. Reviewed

Yamamoto H, Tanaka S, Kasugai D, Shimizu M, Tsuchikawa Y, Hori Y, Fugane Y, Inoue T, Nagaya M, Omote N, Higashi M, Yamamoto T, Jingushi N, Numaguchi A, Goto Y, Nishida Y.

Sci Rep. Vol. 13 ( 1 ) page： 14529 - 14529 2023.9

Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo. Reviewed Open Access

Zhang J, Nishida Y, Koike H, Zhuo L, Ito K, Ikuta K, Sakai T, Imagama S.

Int J Mol Sci. Vol. 24 ( 15 ) page： 12422 - 12422 2023.8

In-Hospital Fall Risk Prediction by Objective Measurement of Lower Extremity Function in a High-Risk Population. Reviewed

Tanaka S, Imaizumi T, Morohashi A, Sato K, Shibata A, Fukuta A, Nakagawa R, Nagaya M, Nishida Y, Hara K, Katsuno M, Suzuki Y, Nagao Y.

J Am Med Dir Assoc. Vol. 23 2023.8

Association between National Institutes of Health Stroke Scale and Functional Independence Measure scores in patients with ischemic stroke from convalescent rehabilitation outcomes. Reviewed

Senda J, Ito K, Kotake T, Mizuno M, Kishimoto H, Yasui K, Nakagawa-Senda H, Katsuno M, Nishida Y, Sobue G.

Nagoya J Med Sci. Vol. 85 ( 3 ) page： 428 - 443 2023.8

整形外科医の手による骨・軟部腫瘍の医師主導治験への道腱滑膜巨細胞腫に対するザルトプロフェンを用いた医師主導治験(REALIZE study)の立案と実施 Reviewed

武内章彦, 遠藤誠, 川井章, 西田佳弘, 寺内竜, 松峯昭彦, 相羽久輝, 中村知樹, 尾崎敏文, 星学, 土屋弘行

日本整形外科学会雑誌 Vol. 97 ( 8 ) page： S1557 - S1557 2023.8

Hand Grip Strength Assessment Based on Sarcopenia Diagnostic Criteria Predicts Swallowing Function. Reviewed

Okada T, Yamaguchi H, Tanaka S, Koyama K, Hishida A, Konno S, Nakamura M, Sugiura H, Nishida Y.

Dysphagia. 2023.7

A phase 1 trial of NY-ESO-1-specific TCR-engineered T-cell therapy combined with a lymph node-targeting nanoparticulate peptide vaccine for the treatment of advanced soft tissue sarcoma. Reviewed

Ishihara M, Nishida Y, Kitano S, Kawai A, Muraoka D, Momose F, Harada N, Miyahara Y, Seo N, Hattori H, Takada K, Emori M, Kakunaga S, Endo M, Matsumoto Y, Sasada T, Sato E, Yamada T, Matsumine A, Nagata Y, Watanabe T, Kageyama S, Shiku H.

Int J Cancer. Vol. 152 ( 12 ) page： 2554 - 2566 2023.6

叢状神経線維腫に対するMEK阻害剤セルメチニブの期待と注意事項 Reviewed

西田佳弘, 野々部典枝, 城所博之, 加藤太一, 武市拓也, 生田国大, 今釜史郎

日本整形外科学会雑誌 Vol. 97 ( 6 ) page： S1427 - S1427 2023.6

叢状神経線維腫に対するMEK阻害剤セルメチニブの期待と注意事項 Reviewed

西田佳弘, 野々部典枝, 城所博之, 加藤太一, 武市拓也, 生田国大, 今釜史郎

日本整形外科学会雑誌 Vol. 97 ( 6 ) page： S1427 - S1427 2023.6

Selumetinib in Japanese pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas: An open-label, phase I study. Reviewed

Suenobu S, Terashima K, Akiyama M, Oguri T, Watanabe A, Sugeno M, Higashimori M, So K, Nishida Y.

Neurooncol Adv. Vol. 5 ( 1 ) 2023.5

Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling. Reviewed Open Access

Mori N, Esaki N, Shimoyama Y, Shiraki Y, Asai N, Sakai T, Nishida Y, Takahashi M, Enomoto A, Mii S.

Pathol Res Pract. Vol. 245 page： 154443 - 154443 2023.5

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. Reviewed Open Access

Nakajima H, Yamaguchi J, Takami H, Hayashi M, Kodera Y, Nishida Y, Watanabe N, Onoe S, Mizuno T, Yokoyama Y, Ebata T.

Int J Clin Oncol. Vol. 28 ( 5 ) page： 688 - 697 2023.5

膝関節に発生した樹枝状脂肪腫に対して人工関節置換術を施工した1症例 Reviewed

高橋裕, 藤林孝義, 柘植峻, 大倉俊昭, 西田佳弘

中部日本整形外科災害外科学会雑誌 Vol. 66 ( 3 ) page： 475 - 476 2023.5

Genomic patterns of malignant peripheral nerve sheath tumor (MPNST) evolution correlate with clinical outcome and are detectable in cell-free DNA. Reviewed

Cortes-Ciriano I, Steele CD, Piculell K, Al-Ibraheemi A, Eulo V, Bui MM, Chatzipli A, Dickson BC, Borcherding DC, Feber A, Galor A, Hart J, Jones KB, Jordan JT, Kim RH, Lindsay D, Miller C, Nishida Y, Proszek PZ, Serrano J, Sundby RT, Szymanski JJ, Ullrich NJ, Viskochil D, Wang X, Snuderl M, Park PJ, Flanagan AM, Hirbe AC, Pillay N, Miller DT.

Cancer Discov. Vol. 13 ( 3 ) page： 654 - 671 2023.3

Clinical results of active surveillance for extra-abdominal desmoid-type fibromatosis. Reviewed

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

Cancer Med. Vol. 12 ( 5 ) page： 5245 - 5254 2023.3

Nakashima Y, Yokoyama Y, Ogawa H, Sakakibara A, Sunagawa M, Nishida Y, Mizuno T, Yamaguchi J, Onoe S, Watanabe N, Kawakatsu S, Igami T, Ebata T.

Int J Clin Oncol. Vol. 28 ( 3 ) page： 482 - 490 2023.3

Investigation of inpatient convalescent rehabilitation outcomes in branch atheromatous disease. Reviewed

Senda J, Ito K, Kotake T, Mizuno M, Kishimoto H, Yasui K, Katsuno M, Nishida Y, Sobue G.

J Stroke Cerebrovasc Dis. Vol. 32 ( 3 ) 2023.3

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG). Reviewed

Morii T, Anazawa U, Sato C, Iwata S, Nakagawa M, Endo M, Nakamura T, Ikuta K, Nishida Y, Nakayama R, Udaka T, Kawamoto T, Kito M, Sato K, Imanishi J, Akiyama T, Kobayashi H, Nagano A, Outani H, Toki S, Nishisho T, Sasa K, Suehara Y, Kawano H, Ueda T, Morioka H.

Eur J Surg Oncol. Vol. 49 ( 2 ) page： 353 - 361 2023.2

Hyaluronan in articular cartilage: analysis of hip osteoarthritis and osteonecrosis of femoral head. Reviewed Open Access

Zhang J, Nishida Y, Koike H, Ito K, Zhuo L, Nishida K, Kimata K, Ikuta K, Sakai T, Urakawa H, Seki T, Imagama S.

J Orthop Res. Vol. 41 ( 2 ) page： 307 - 315 2023.2

Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients. Reviewed Open Access

Tsuchikawa Y, Tokuda Y, Ito H, Shimizu M, Tanaka S, Nishida K, Takagi D, Fukuta A, Takeda N, Yamamoto H, Hori M, Nishida Y, Mutsuga M.

Circ J. Vol. 87 ( 2 ) page： 306 - 311 2023.1

Case report: Novel NIPBL-BEND2 fusion gene identified in osteoblastoma-like phosphaturic mesenchymal tumor of the fibula. Reviewed Open Access

Sakai T, Okuno Y, Murakami N, Shimoyama Y, Imagama S, Nishida Y.

Front Oncol. 2023.1

左大腿骨近位部に生じた二次性動脈瘤様骨嚢腫を合併した線維性骨異形成の検討 Reviewed

加藤雅崇, 小澤英史, 長田直大, 都野田真健, 今釜史郎, 西田佳弘

中部日本整形外科災害外科学会雑誌 Vol. 66 ( 1 ) page： 99 - 100 2023.1

Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306. Reviewed

Tanaka K, Machida R, Kawai A, Nakayama R, Tsukushi S, Asanuma K, Matsumoto Y, Hiraga H, Hiraoka K, Watanuki M, Yonemoto T, Abe S, Katagiri H, Nishida Y, Nagano A, Suehara Y, Kawashima H, Kawano M, Morii T, Hatano H, Toguchida J, Okuma T, Takeyama M, Takenaka S, Akisue T, Furuta T, Emori M, Hiruma T, Outani H, Yamamoto T, Kataoka T, Fukuda H, Ozaki T, Iwamoto Y.

Br J Cancer. Vol. 127 ( 8 ) page： 1487 - 1496 2022.11

Surgical Treatment and Complications of Deep-Seated Nodular Plexiform Neurofibromas Associated with Neurofibromatosis Type 1. Reviewed Open Access

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

J Clin Med. Vol. 11 ( 19 ) page： 5695 - 5695 2022.9

A clinical trial of a unidirectional porous tricalcium phosphate filling for defects after resection of benign bone lesions: a prospective multicenter study. Reviewed

Ikuta K, Nishida Y, Ota T, Tsukushi S, Kozawa E, Nakashima H, Yamada K, Yamashita S, Imagama S.

Sci Rep. Vol. 12 ( 1 ) page： 16060 - 16060 2022.9

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: The REALIZE study. Reviewed Open Access

Takeuchi A, Endo M, Kawai A, Nishida Y, Terauchi R, Matsumine A, Aiba H, Nakamura T, Tandai S, Ozaki T, Hoshi M, Kayano D, Okuda M, Yamamoto N, Hayashi K, Miwa S, Igarashi K, Yoshimura K, Nomura A, Murayama T, Tsuchiya H.

Front Oncol. Vol. 12 2022.9

Tsukushi S, Nishida Y, Hirose T, Nakata E, Nakagawa R, Nakamura T, Imanishi J, Nagano A, Tamiya H, Ueda T; and Japanese Musculoskeletal Oncology Group (JMOG).

BMC Cancer. Vol. 22 ( 1 ) page： 781 - 781 2022.7

Efficacy of auranofin as an inhibitor of desmoid progression. Reviewed Open Access

Ito K, Nishida Y, Hamada S, Shimizu K, Sakai T, Ohkawara B, Alman BA, Enomoto A, Ikuta K, Koike H, Zhang J, Ohno K, Imagama S.

Sci Rep. Vol. 12 ( 1 ) page： 11918 - 11918 2022.7

Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi-institutional study. Reviewed

Kozawa E, Nishida Y, Kawai A, Hayakawa K, Nokitaka S, Kawashima H, Iwata S, Tsuchiya H, Tsukushi S, Takenaka S, Imanishi J, Baba I, Nagano A, Morii T, Shirai T, Shimizu K, Kawano H.

Cancer Sci. Vol. 113 ( 7 ) page： 2397 - 2408 2022.7

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

Yamashita K, Funauchi Y, Hayakawa K, Ae K, Matsumoto S, Ikuta K, Nishida Y, Ueno T, Shimoyama Y, Hiruta N, Machinami R, Kawachi H, Takeuchi K.

Virchows Arch. Vol. 480 ( 6 ) page： 1269 - 1275 2022.6

転移性骨腫瘍の新たな展開デュアルコンセプトの骨転移治療法開発抗腫瘍と骨形成促進効果 Reviewed

西田佳弘, 大田剛広, 生田国大, 鈴木喜貴, 小池宏, 相羽久輝, 木村浩明, 酒井智久, 伊藤鑑, 村上英樹, 今釜史郎

日本整形外科学会雑誌 Vol. 96 ( 6 ) page： S1275 - S1275 2022.6

Tail-like lesionを有する悪性軟部腫瘍に対する術前療法の効果に関する検討東海骨軟部腫瘍コンソーシアム多施設共同研究 Reviewed

相羽久輝, 生田国大, 淺沼邦洋, 河南勝久, 筑紫聡, 松峯昭彦, 石村大輔, 永野昭仁, 紫藤洋二, 小澤英史, 山田健志, 和佐潤志, 木村浩明, 酒井貴央, 村上英樹, 酒井智久, 中村知樹, 西田佳弘

日本整形外科学会雑誌 Vol. 96 ( 6 ) page： S1364 - S1364 2022.6

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

Kawai A, Araki N, Ae K, Akiyama T, Ozaki T, Kawano H, Kunisada T, Sumi M, Takahashi S, Tanaka K, Tsukushi S, Naka N, Nishida Y, Miyachi M, Yamamoto N, Yoshida A, Yonemoto T, Yoshida M, Iwata S.

J Orthop Sci. Vol. 27 ( 3 ) page： 533 - 550 2022.5

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

Urakawa H, Nagano A, Machida R, Tanaka K, Kataoka T, Sekino Y, Nishida Y, Takahashi M, Kunisada T, Kawano M, Yoshida Y, Takagi T, Sato K, Hiruma T, Hatano H, Tsukushi S, Sakamoto A, Akisue T, Hiraoka K, Ozaki T.

Jpn J Clin Oncol. Vol. hyac071 2022.4

Possible Repositioning of an Oral Anti-Osteoporotic Drug, Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase. Reviewed Open Access

Koike H, Nishida Y, Shinomura T, Ohkawara B, Ohno K, Zhuo L, Kimata K, Ushida T, Imagama S.

Int J Mol Sci. Vol. 23 ( 8 ) page： 4089 - 4089 2022.4

Surgical treatment for extremity rhabdomyosarcoma: longitudinal national questionnaire survey in Japan. Reviewed

Nishida Y, Kawai A.

Jpn J Clin Oncol Vol. 52 ( 4 ) page： 362 - 369 2022.4

Effects of Neuromuscular Electrical Stimulation on Lower Limb Muscle Strength After Living Donor Liver Transplant: A Case-Control Study. Reviewed

Hattori K, Mizuno Y, Ogura Y, Inoue T, Nagaya M, Jobara K, Kurata N, Nishida Y.

Transplant Proc. Vol. 54 ( 3 ) page： 749 - 754 2022.4

西田佳弘, 生田国大, 夏目敦至, 森川真紀, 城所博之, 野々部典枝, 武市拓也, 神戸未来, 尾崎紀夫, 今釜史郎

日本整形外科学会雑誌 Vol. 96 ( 3 ) page： S602 - S602 2022.3

Long-Term Results of Kyocera Modular Limb Salvage System after Resection of Tumors in the Distal Part of the Femur: Report from Japanese Musculoskeletal Oncology Group Study. Reviewed Open Access

Nakamura T, Matsumine A, Toda Y, Takenaka S, Outani H, Fujiwara T, Nishida Y, Tsukushi S, Tome Y, Kawamoto T, Kito M, Shinohara N, Tomita M, Torigoe T, Sudo A, Kawano H.

Cancers (Basel) Vol. 14 ( 4 ) page： 870 - 870 2022.2

Clinical outcome in patients who underwent amputation due to extremity soft tissue sarcoma: Tokai Musculoskeletal Oncology Consortium study. Reviewed

Hagi T, Nakamura T, Nagano A, Koike H, Yamada K, Aiba H, Fujihara N, Wasa J, Asanuma K, Kozawa E, Ishimura D, Kawanami K, Izubuchi Y, Shido Y, Sudo A, Nishida Y.

Jpn J Clin Oncol Vol. 52 ( 2 ) page： 157 - 162 2022.2

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 Manag Res. Vol. 13 page： 8473 - 8480 2021.11

Trends in diagnostic and therapeutic strategies for extra-abdominal desmoid-type fibromatosis: Japanese musculoskeletal oncology group questionnaire survey. Reviewed

Murase F, Nishida Y, Hamada S, Sakai T, Shimizu K, Ueda T.

Jpn J Clin Oncol. Vol. 51 ( 11 ) page： 1615 - 1621 2021.11

Response to Letter to the Editor. Reviewed

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

Arthritis Rheumatol. Vol. 73 ( 11 ) page： 2148 - 2149 2021.11

Pathophysiology of Hyaluronan Accumulation/Depolymerization in Osteoarthritic Joints. Reviewed

Nishida Y.

Am J Pathol. Vol. 191 ( 11 ) page： 1963 - 1965 2021.11

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review. Reviewed

Emori M, Matsumoto Y, Murahashi Y, Yoshida M, Nishida Y.

Nagoya J Med Sci. Vol. 83 ( 4 ) page： 673 - 681 2021.11

Diffusion-weighted magnetic resonance imaging improves the accuracy of differentiation of benign from malignant peripheral nerve sheath tumors. Reviewed

Koike H, Nishida Y, Ito S, Shimoyama Y, Ikuta K, Urakawa H, Sakai T, Shimizu K, Ito K, Imagama S.

World Neurosurg. Vol. S1878-8750 ( 21 ) page： 01483-2 - 01483-2 2021.10

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

Ikuta K, Nishida Y, Tsukushi S, Sakai T, Koike H, Imagama S.

Knee. Vol. 33 page： 102 - 109 2021.10

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

生田国大, 西田佳弘, 杉浦英志, 今釜史郎

別冊整形外科 ( 80 ) page： 113 - 116 2021.10

【骨・軟部腫瘍のマネジメント（その２）】良性骨腫瘍・腫瘍類似疾患の治療　類骨骨腫　類骨骨腫に対するO-armガイド下手術の有用性 Reviewed

小池宏, 西田佳弘, 生田国大, 酒井智久, 伊藤鑑, 今釜史郎

別冊整形外科 ( 80 ) page： 71 - 73 2021.10

Less-invasive fascia-preserving surgery for abdominal wall desmoid. Reviewed Open Access

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

Sci Rep. Vol. 11 ( 1 ) page： 19379 - 19379 2021.9

Pathophysiology of Hyaluronan Accumulation/Depolymerization in Osteoarthritic Joints. Reviewed Open Access

Nishida Y.

Am J Pathol. Vol. S0002－9440 ( 21 ) page： 00380 - 00381 2021.9

Efficacy and safety of diclofenac-hyaluronate conjugate(diclofenac etalhyaluronate) for knee osteoarthritis: a randomaized phase 3 trial in Japan. Reviewed

Yoshihiro Nishida, Kazuyuki Kano, Yuji Nobuoka, Takayuki Seo.

Arthritis Rheumatol. Vol. 73 ( 9 ) page： 1646 - 1655 2021.9

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

Ota T, Nishida Y, Ikuta K, Tsukushi S, Yamada K, Kozawa E, Urakawa H, Imagama S.

Sci Rep. Vol. 11 ( 1 ) page： 17384 - 17384 2021.8

Spontaneous Regression of Brown Tumor in a Patient Treated With Peritoneal Dialysis. Reviewed Open Access

Ito K, Ikuta K, Nishida Y, Sakai T, Imagama S.

Cureus. Vol. 13 ( 8 ) page： e17078 - e17078 2021.8

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

Aiba H, Ikuta K, Asanuma K, Kawanami K, Tsukushi S, Matsumine A, Ishimura D, Nagano A, Shido Y, Kozawa E, Yamada K, Wasa J, Kimura H, Sakai T, Murakami H, Sakai T, Nakamura T, Nishida Y.

Cancers (Basel). Vol. 13 ( 15 ) page： 3901 - 3901 2021.8

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

家崎雄介, 生田国大, 酒井智久, 小池宏, 今釜史郎, 西田佳弘

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

A Novel Technique to Lengthen the Reverse Latissimus Dorsi Muscle Flap Arc. Reviewed

Takanari K, Nakamura Y, Uchibori T, Nakamura R, Ebisawa K, Kambe M, Urakawa H, Nishida Y, Kamei Y.

Plast Reconstr Surg Glob Open. Vol. 9 ( 7 ) page： 3525 - 3525 2021.7

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

Ito K, Nishida Y, Ikuta K, Urakawa H, Koike H, Sakai T, Zhang J, Shimoyama Y, Imagama S.

J Orthop Surg Res. Vol. 16 ( 1 ) page： 439 - 439 2021.7

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

Nishida Y, Ikuta K, Natsume A, Ishihara N, Morikawa M, Kidokoro H, Muramatsu Y, Nonobe N, Ishizuka K, Takeichi T, Kanbe M, Mizuno S, Imagama S, Ozaki N.

Sci Rep. Vol. 11 ( 1 ) page： 11933 - 11933 2021.6

Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer. Reviewed

Tanaka S, Ozeki N, Mizuno Y, Nakajima H, Hattori K, Inoue T, Nagaya M, Fukui T, Nakamura S, Goto M, Sugiyama T, Nishida Y, Chen-Yoshikawa TF.

J Cachexia Sarcopenia Muscle. Vol. 12 ( 3 ) page： 646 - 656 2021.6

腱滑膜巨細胞腫患者を対象としたpexidartinibの多施設共同、2パート、非盲検、単群、国内第II相臨床試験デザイン Reviewed

川井章, 武内章彦, 遠藤誠, 角永茂樹, 井上悟, 菊森久仁佳, 井上裕之, 金井由奈, 西田佳弘

日本整形外科学会雑誌 Vol. 95 ( 6 ) page： S1335 - S1335 2021.6

Short-range UV-LED irradiation in postmenopausal osteoporosis using ovariectomized mice. Reviewed Open Access

Ochiai S, Nishida Y, Higuchi Y, Morita D, Makida K, Seki T, Ikuta K, Imagama S.

Sci Rep. Vol. 11 ( 1 ) page： 7875 - 7875 2021.4

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

酒井智久, 西田佳弘, 生田国大, 小池宏, 伊藤鑑, 今釜史郎

別冊整形外科 ( 79 ) page： 55 - 57 2021.4

巻頭言　希少疾患から学び、得られる診療の底力 Reviewed

西田佳弘

日本義肢協会誌 Vol. 125 page： 1 - 1 2021.4

Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up. Reviewed Open Access

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

BMC Musculoskelet Disord. Vol. 22 ( 1 ) page： 233 - 233 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.

Eur J Cancer. Vol. 145 page： 109 - 120 2021.3

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

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

Cancer Sci. Vol. 112 ( 3 ) page： 1114 - 1122 2021.3

骨軟部　良性軟部腫瘍・デスモイド型線維腫症の診断・治療指針 Reviewed

西田佳弘

最新腫瘍文献とガイドラインでみる整形外科学レビュー2021-'22 page： 239 - 244 2021.3

初発悪性軟部腫瘍における四肢切・離断症例の治療成績東海骨軟部腫瘍コンソーシアム共同研究 Reviewed

萩智仁, 中村知樹, 永野昭仁, 酒井智久, 山田健志, 相羽久輝, 筑紫聡, 片桐浩久, 淺沼邦洋, 須藤啓広, 西田佳弘

日本整形外科学会雑誌 Vol. 95 ( 3 ) page： S892 - S892 2021.3

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

Yoshihiro Nishida and Kunihiro Ikuta

Nagoya J Med Sci. Vol. 83 ( 1 ) page： 217 - 218 2021.2

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

加藤万結, 服部浩佳, 川田しお梨, 秋田直洋, 関水匡大, 小野学, 二村昌樹, 後藤雅彦, 堀部敬三, 生田国大, 新井英介, 西田佳弘, 前田尚子

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

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. Reviewed International journal Open Access

Yoshihiro Nishida, Hiroshi Urakawa, Robert Nakayama, Eisuke Kobayashi, Toshifumi Ozaki, Keisuke Ae, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Takahiro Goto, Hiroaki Hiraga, Norifumi Naka, Shunji Takahashi, Yuichi Ando, Masahiko Ando, Yachiyo Kuwatsuka, Shunsuke Hamada, Takafumi Ueda, Akira Kawai

Int J Cancer Vol. 148 ( 1 ) page： 140 - 149 2021.1

Language：English Publishing type：Research paper (scientific journal)

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

DOI： 10.1002/ijc.33201

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

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.

Clin Orthop Relat Res. Vol. 478 ( 11 ) page： 2537 - 2547 2020.11

Effectiveness of doxorubicin-based and liposomal doxorubicin chemotherapies for patients with extra-abdominal desmoid-type fibromatosis: A systematic review. Reviewed Open Access

Koki Shimizu, Hiroyuki Kawashima, Akira Kawai, Masahiro Yoshida, Yoshihiro Nishida

Jpn J Clin Oncol. Vol. 50 ( 11 ) page： 1274 - 1281 2020.11

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

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

Jpn J Clin Oncol Vol. 50 ( 9 ) page： 1037 - 1042 2020.9

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

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

Jpn J Clin Oncol. Vol. 50 ( 9 ) page： 1032 - 1036 2020.9

Forced Expression of KIAA1199, a Novel Hyaluronidase, Inhibits Tumorigenicity of Low-Grade Chondrosarcoma Reviewed Open Access

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

J Orthop Res. Vol. 38 ( 9 ) page： 1942 - 1951 2020.9

膝蓋骨および大腿四頭筋の広範欠損に対して大腿筋膜付き前外側大腿皮弁による機能的再建を行った1例 Reviewed

伊藤弘幸, 高成啓介, 中村優, 蛯沢克巳, 神戸未来, 内堀貴文, 宮永亨, 新井英介, 西田佳弘, 亀井讓

日本形成外科学会会誌 Vol. 40 ( 9 ) page： 489-496 2020.9

膝蓋骨および大腿四頭筋の広範欠損に対して大腿筋膜付き前外側大腿皮弁による機能的再建を行った1例 Reviewed

伊藤弘幸, 高成啓介, 中村優, 蛯沢克己, 神戸未来, 内堀貴文, 宮永亨, 新井英介, 西田佳弘, 亀井譲

日本形成外科学会会誌 Vol. 40 ( 9 ) page： 489 - 496 2020.9

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 J Surg Oncol. Vol. 18 ( 1 ) page： 227 - 227 2020.8

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

Kenta Ishii, Yukihiro Yokoyama, Yoshihiro Nishida, Suguru Yamada, Yasuhiro Kodera, Naoto Sassa, Momokazu Gotoh, Masato Nagino

Jpn J Clin Oncol Vol. - ( - ) page： 10.1093/jjco/hyaa126. - 1418 2020.7

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

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

Sci Rep. Vol. 10 ( 1 ) page： 11892 2020.7

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

Jap J Clin Oncol. Vol. 50 ( 7 ) page： 772 - 778 2020.7

Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas Reviewed

Urakawa H, Kawai A, Goto T, Hiraga H, Ozaki T, Tsuchiya H, Nakayama R, Naka N, Matsumoto Y, Kobayashi E, Okuma T, Kunisada T, Ando M, Ueda T, Nishida Y

Cancer Sci. Vol. - ( - ) page： 10.1111/cas.14542. - 3312 2020.6

Risk Factors of Local Recurrence after Surgery in Extra-Abdominal Desmoid-Type Fibromatosis:A Multicenter Study in Japan. Reviewed

Nishida Y, Hamada S, Kawai A, Kunisada T, Ogose A, Matsumoto Y, Ae K, Toguchida J, Ozaki T, Hirakawa A, Motoi T, Sakai T, Kobayashi E, Gokita T, Okamoto T, Matsunobu T, Shimizu K, Koike H

Cancer Sci. Vol. - ( - ) page： 10.1111/cas.14528. - 2942 2020.6

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

Fujita K, Nakashima H, Kako M, Shibata A, Yu-Ting C, Tanaka S, Nishida Y, Kuzuya M

Arch Gerontol Geriatr. Vol. 90 page： 104155 2020.6

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

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

Int J Cancer. Vol. 146 ( 12 ) page： 3504 - 3515 2020.6

A case of retroperitoneal dedifferentiated liposarcoma successfully treated by neoadjuvant chemotherapy and subsequent surgery. Reviewed Open Access

Yokoyama Y, Nishida Y, Ikuta K, Nagino M.

Surg Case Rep. Vol. 6 ( 1 ) page： 105 - 105 2020.5

Definitive radiation therapy in patients with unresectable desmoid tumors: A systematic review. Reviewed International journal Open Access

Matsunobu T, Kunisada T, Ozaki T, Iwamoto Y, Yoshida M, Nishida Y

Jpn J Clin Oncol Vol. 50 ( 5 ) page： 568 - 573 2020.5

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1093/jjco/hyaa007

How Many Steps Per Day are Necessary to Prevent Postoperative Complications Following Hepato-Pancreato-Biliary Surgeries for Malignancy? Reviewed

全身性強皮症および多発性筋炎のオーバーラップ症候群に合併したⅡ型呼吸不全に対して呼吸器リハビリテーション治療が有効であった1例 Reviewed Open Access

岡田貴士, 門野泉, 金野鈴奈, 杉山純也, 菱田愛加, 西田佳弘, 杉浦英志

The Japanese Journal of Rehabilitation Medicine Vol. 57 ( 5 ) page： 468 - 473 2020.5

Clinical characteristics and surgical outcomes of retroperitoneal tumors: a comprehensive data collection from multiple departments. Reviewed

Sassa N, Yokoyama Y, Nishida Y, Yamada S, Uchida H, Kajiyama H, Nagino M, Kodera Y, Gotoh M

Int J Clin Oncol Vol. 25 ( 5 ) page： 929-936 - 936 2020.5

Nakajima H, Yokoyama Y, Inoue T, Nagaya M, Mizuno Y, Kayamoto A, Nishida Y, Nagino M

Ann Surg Oncol Vol. 27 ( 5 ) page： 1387 - 1397 2020.5

Usefulness of surgical treatment for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis: A systematic review and meta-analysis. Reviewed International journal Open Access

Kito M, Ogose A, Yoshida M, Nishida Y

Jpn J Clin Oncol Vol. 50 ( 5 ) page： 574 - 580 2020.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The purpose of this systematic review is to assess and compare the efficacy of surgical treatment for patients with asymptomatic extra-peritoneal desmoid-type fibromatosis to the wait-and-see policy by evaluating (1) the exacerbation rate (exacerbation; recurrence after surgery or progressive disease following non-surgical treatment) and (2) treatment-associated complications in extra-peritoneal desmoid-type fibromatosis. METHODS: We evaluated documents published between 1 January 1990 and 31 August 2017. The risk of bias in the selected literature was analyzed using the Cochrane Collaboration Risk of Bias Tool. Quality of evidence was evaluated using Grading of Recommendation, Assessment, Development and Evaluation approach. RESULTS: One prospective cohort study, four case-control studies and five case series studies were identified. Meta-analysis was performed to evaluate the exacerbation rate after treatment on one prospective cohort study and four case-control studies. In comparing surgical and non-surgical treatments, the exacerbation rate was significantly higher in the surgical treatment group (odds ratio: 1.32, 95% confidence interval 1.01-1.73, P = 0.05). However, in the case series study, the recurrence rate was 23.4% for the surgical treatment group, while the progressive disease rate was 28.1% for the non-surgical treatment group. The postoperative complication rates associated with surgical treatment in the two studies were 20.8 and 17.2%, respectively. CONCLUSIONS: When considering the exacerbation rate, non-surgical treatment might be appropriate for asymptomatic patients with extra-peritoneal desmoid-type fibromatosis. However, if patients with tumor-related symptoms opt for surgery, including those who face difficulties due to the presence of tumors, it is important to fully explain to them the possibility that the recurrence rate and treatment-associated functional failures may increase depending on the site of occurrence.

DOI： 10.1093/jjco/hyaa009

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

全身性強皮症および多発性筋炎のオーバーラップ症候群に合併したⅡ型呼吸不全に対して呼吸器リハビリテーション治療が有効であった1例 Open Access

岡田貴士, 門野泉, 金野鈴奈, 杉山純也, 菱田愛加, 西田佳弘, 杉浦英志

The Japanese Journal of Rehabilitation Medicine Vol. 57 ( 5 ) page： 468-473 2020.5

Efficacy of low dose chemotherapy with methotrexate and vinblastine for patients with extra-abdominal desmoid-type fibromatosis : A systematic review. Reviewed

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

Jpn J Clin Oncol Vol. 50 ( 4 ) page： 419-424 - 424 2020.4

Genomics of MPNST (GeM) Consortium: Rationale and Study Design for Multi-Omic Characterization of NF1-Associated and Sporadic MPNSTs. Reviewed International coauthorship Open Access

Miller DT, Cortés-Ciriano I, Pillay N, Hirbe AC, Snuderl M, Bui MM, Piculell K, Al-Ibraheemi A, Dickson BC, Hart J, Jones K, Jordan JT, Kim RH, Lindsay D, Nishida Y, Ullrich NJ, Wang X, Park PJ, Flanagan AM

Genes (Basel). Vol. 11 ( 4 ) page： e387 2020.4

上腕骨近位部の骨表面に発生したグロムス腫瘍の1例 Reviewed

杉浦喬也, 生田国大, 新井英介, 酒井智久, 小池宏, 西田佳弘

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

上腕骨近位部の骨表面に発生したグロムス腫瘍の1例

杉浦喬也, 生田国大, 新井英介, 酒井智久, 小池宏, 西田佳弘

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

当院における肩・上腕の骨・軟部腫瘍切除後の再建症例に対する術後患肢機能の検討 Reviewed

中村優, 高成啓介, 蛯沢克己, 内堀貴文, 神戸未来, 落合美奈, 鈴木寛久, 浜田俊介, 亀井譲, 西田佳弘

日本手外科学会雑誌 Vol. 37 ( 1 ) page： O21 - 5 2020.4

Preoperative six-minute walk distance as a predictor of postoperative complication in patients with esophageal cancer. Reviewed

Inoue T, Ito S, Kanda M, Niwa Y, Nagaya M, Nishida Y, Hasegawa Y, Koike M, Kodera Y

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Vol. 33 ( 2 ) page： doz050 - doz050 2020.3

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

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association Vol. 25 ( 2 ) page： 319 - 323 2020.3

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1016/j.jos.2019.04.008

デスモイド型線維腫症に対する放射線単独治療に関するシステマティックレビュー Reviewed

松延知哉, 国定俊之, 尾崎敏文, 岩本幸英, 西田佳弘

日本整形外科学会雑誌 Vol. 94 ( 3 ) page： S681 - S681 2020.3

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

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

Heliyon Vol. 6 ( 2 ) page： e03499 2020.2

Targetable driver mutations in multicentric reticulohistiocytosis. Reviewed International journal Open Access

Norihiro Murakami, Tomohisa Sakai, Eisuke Arai, Hideki Muramatsu, Daisuke Ichikawa, Shuji Asai, Yoshie Shimoyama, Naoki Ishiguro, Yoshiyuki Takahashi, Yusuke Okuno, Yoshihiro Nishida

Haematologica Vol. 105 ( 2 ) page： E61 - E64 2020.1

The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma. Reviewed

Heng M, Gupta A, Chung PW, Healey JH, Vaynrub M, Rose PS, Houdek MT, Lin PP, Bishop AJ, Hornicek FJ, Chen YL, Lozano-Calderon S, Holt GE, Han I, Biau D, Niu X, Bernthal NM, Ferguson PC, Wunder JS; Japanese Musculoskeletal Oncology Group (JMOG, Nishida Y included); Soft Tissue Osteosarcoma International Collaborative (STOIC).

Eur J Cancer. Vol. 125 page： 130-141 2020.1

Massively parallel sequencing of tenosynovial giant cell tumors reveals novel CSF1 fusion transcripts and novel somatic CBL mutations. Reviewed International journal Open Access

Yusuke Tsuda, Makoto Hirata, Kotoe Katayama, Toru Motoi, Daisuke Matsubara, Yoshinao Oda, Masashi Fujita, Hiroshi Kobayashi, Hirotaka Kawano, Yoshihiro Nishida, Tomohisa Sakai, Tomotake Okuma, Takahiro Goto, Koichi Ogura, Akira Kawai, Keisuke Ae, Ukei Anazawa, Yoshiyuki Suehara, Shintaro Iwata, Satoru Miyano, Seiya Imoto, Tatsuhiro Shibata, Hidewaki Nakagawa, Rui Yamaguchi, Sakae Tanaka, Koichi Matsuda

International journal of cancer Vol. 145 ( 12 ) page： 3276 - 3284 2019.12

Language：English Publishing type：Research paper (scientific journal)

Tenosynovial giant cell tumor (TSGCT) is a rare neoplasm. Although surgical resection is the widely accepted primary treatment for TSGCT, recurrences are frequent, and patients' joint function may be severely compromised. Previous studies reported that CSF1-COL6A3 fusion genes were identified in approximately 30% of TSGCTs. The aim of our study was to comprehensively clarify the genomic abnormalities in TSGCTs. We performed whole exome sequencing in combination with target sequence validation on 34 TSGCT samples. RNA sequencing was also performed on 18 samples. RNA sequencing revealed fusion transcripts involving CSF1, including novel CSF1-VCAM1, CSF1-FN1 and CSF1-CDH1 fusions, in 13/18 (72%) cases. These fusion genes were validated by chromogenic in situ hybridization. All CSF1 fusions resulted in the deletion of CSF1 exon 9, which was previously shown to be an important negative regulator of CSF1 expression. We also found that 12 (35%) of the 34 TSGCT samples harbored CBL missense mutations. All mutations were detected in exons 8 or 9, which encode the linker and RING finger domain. Among these mutations, C404Y, L380P and R420Q were recurrent. CBL-mutated cases showed higher JAK2 expression than wild-type CBL cases (p = 0.013). CSF1 fusion genes and CBL mutations were not mutually exclusive, and both alterations were detected in six of the 18 (33%) tumors. The frequent deletion of CSF1 exon 9 in the fusion transcripts suggested the importance of this event in the etiology of TSGCT. Our results may contribute to the development of new targeted therapies using JAK2 inhibitors for CBL-mutated TSGCT.

DOI： 10.1002/ijc.32421

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

Integrated Exome and RNA Sequencing of Dedifferentiated Liposarcoma. Reviewed

Makoto Hirata, Naofumi Asano, Kotoe Katayama, Akihiko Yoshida, Yusuke Tsuda, Masaya Sekimizu, Sachiyo Mitani, Eisuke Kobayashi, Motokiyo Komiyama, Hiroyuki Fujimoto, Takahiro Goto, Yukihide Iwamoto, Norifumi Naka, Shintaro Iwata, Yoshihiro Nishida, Toru Hiruma, Hiroaki Hiraga, Hirotaka Kawano, Toru Motoi, Yoshinao Oda, Daisuke Matsubara, Masashi Fujita, Tatsuhiro Shibata, Hidewaki Nakagawa, Robert Nakayama, Tadashi Kondo, Seiya Imoto, Satoru Miyano, Akira Kawai, Rui Yamaguchi, Hitoshi Ichikawa, and Koichi Matsuda

Nat Commun Vol. 10 ( 1 ) page： 5683 2019.12

Clinical Frailty Scale Score Before ICU Admission Is Associated With Mobility Disability in Septic Patients Receiving Early Rehabilitation. Reviewed

Nakajima H, Nishikimi M, Shimizu M, Hayashi K, Inoue T, Nishida K, Takahashi K, Matsui S, Nishida Y, Matsuda N.

Crit Care Explor. Vol. 1 ( 12 ) page： e0066 2019.12

The prognostic role of β-catenin mutations in desmoid-type fibromatosis undergoing resection only: a meta-analysis of individual patient data. Reviewed

Milea J.M. Timbergen, Chiara Colombo, Michel Renckens, Hee Sung Kim, Joost van Rosmalen, Sébastien Salas, John T, Mullen, MD, Piergiuseppe Colombo, Yoshihiro Nishida, MD, Erik A.C. Wiemer, Cornelis Verhoef, Stefan Sleijfer, Alessandro Gronchi, Dirk J. Grünhagen

Ann Surg. Vol. - ( - ) page： 10.1097/SLA.0000000000003698. - 1101 2019.12

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

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

Clinical Features of Thoracic Myelopathy: A Single-Center Study. Reviewed

Ando K, Imagama S, Kobayashi K, Ito K, Tsushima M, Morozumi M, Tanaka S, Machino M, Ota K, Nakashima H, Nishida Y, Ishiguro N

J Am Acad Orthop Surg Glob Res Rev. Vol. 3 ( 11 ) page： - 2019.11

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

Yoshihiro Nishida, Akira Kawai, Junya Toguchida, Akira Ogose, Keisuke Ae, Toshiyuki Kunisada, Yoshihiro Matsumoto, Tomoya Matsunobu, Kunihiko Takahashi, Kazuki Nishida, Toshifumi Ozaki

International journal of clinical oncology Vol. 24 ( 11 ) page： 1498 - 1505 2019.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Treatment modality of desmoid-type fibromatosis (DF) has changed from surgery with a wide surgical margin to conservative treatment. In this study, tumor characteristics of DF, transition of the treatment modality, and clinical outcome of surgical treatment were analyzed based on data obtained from the bone and soft tissue tumor registry established in Japan. METHODS: Data were collected as registration data and follow-up data. Five hundred and thirty registered cases of DF were identified, including 223 cases with follow-up data with or without surgical treatment. RESULTS: The number of registered patients increased gradually. The frequency of surgical treatment was gradually reduced year by year. The 3-year local recurrence free survival (LRFS) was 77.7%, with tumor location and size tending to correlate with LRFS. Interestingly, there was no significant difference in LRFS between wide and marginal margin (P = 0.34). CONCLUSIONS: The treatment modality has shifted from surgical to conservative treatment, with risk factors for surgical treatment similar to those noted in previous studies. The National registry system is crucial for a rare disease such as DF, and in the future, a population based registry system should be established to better comprehend the actual status of DF.

DOI： 10.1007/s10147-019-01512-z

Pazopanib for progressive desmoid tumours: children, persistant effects, and cost. Reviewed

Nishida Y, Sakai T, Koike H, Ito K.

Lancet Oncol. Vol. 20 ( 10 ) page： e555 2019.10

Treatment of tenosynovial giant-cell tumour types. Reviewed

Nishida Y, Ikuta K

The Lancet. Oncology Vol. 20 ( 8 ) page： E399 - E399 2019.8

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

DOI： 10.1007/s10585-019-09980-3