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/m<sup>2</sup> 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