The aim of the present study was to explore the expression of the cancer testis antigens New York‑esophageal squamous cell carcinoma (NY‑ESO)‑1 and melanoma‑associated antigen (MAGE)‑A4 in high‑grade soft‑tissue sarcoma and to evaluate their association with the standard clinical‑pathological features of surgically treated high‑grade sarcoma patients. The study included 82 patients, and NY‑ESO‑1 and MAGE‑A4 antigen expression was analyzed immunohistochemically. The results revealed NY‑ESO‑1‑ and MAGE‑A4‑positive staining in 58.8 and 52.9% of synovial sarcomas, and 55.6 and 0% of myxoid liposarcomas, respectively. In patients with synovial sarcoma, NY‑ESO‑1 and MAGE‑A4 were expressed in 7 patients, only NY‑ESO‑1 was expressed in 3 patients, and only MAGE‑A4 was expressed in 2 patients. Univariate analysis indicated that a significantly higher MAGE‑A4 expression was observed in younger patients (P<0.001) and those with synovial sarcoma (P<0.001). Multivariate analysis indicated that significantly higher NY‑ESO‑1 expression was observed in patients with synovial sarcoma (P<0.01) and myxoid liposarcoma (P<0.01), and significantly higher MAGE‑A4 expression was observed in patients with synovial sarcoma (P<0.01). In high‑grade sarcomas, the 2‑ and 5‑year overall survival rates based on Kaplan‑Meier estimates were 100 and 81.3% in the NY‑ESO‑1‑positive group, and 69.7 and 53.0% in the NY‑ESO‑1‑negative group, respectively (P=0.049). It was also demonstrated that either NY‑ESO‑1 or MAGE‑A4 was positive in 70.6% of synovial sarcomas. These results indicate that NY‑ESO‑1 and MAGE‑A4 may be useful for the diagnosis of synovial sarcoma. The independent expression of NY‑ESO‑1 and MAGE‑A4, which may help expand the pool of candidates for molecular‑targeted immunotherapy, will be beneficial for synovial sarcoma patients.

Critically ill patients in the intensive care unit (ICU) develop muscle atrophy and decreased physical function. Though neuromuscular electrical stimulation (NMES) therapy has been shown to be effective in preventing this, but its effect on older patients is unknown. To examine the course of critically ill older patients treated with NMES in the ICU and to define the impact of its use. A retrospective cohort study was conducted using older ICU patients (≥65 years) categorized into a control group (n = 20) and an NMES group (n = 22). For subgroup analysis, each group was further classified into pre-old age (65–74 years) and old age (≥75 years). The control group showed significant decrease in muscle thickness during ICU and hospital stay. The NMES group showed lower reduction in muscle thickness and showed decrease in muscle echo intensity during hospital stay, compared to the control group. NMES inhibited decrease in muscle thickness in the pre-old age group versus the old age group. The decreasing effect of NMES on echo intensity during hospital stay manifested only in the pre-old age group. We did not find much difference in physical functioning between the NMES and control groups. Lower limb muscle atrophy reduces in critically ill older patients (≥65 years) with NMES and is pronounced in patients aged < 75 years. The impact of NMES on the physical functioning of older patients in ICU needs to be further investigated.

Mesenchymal stromal cell transplantation alone is insufficient when motor dysfunction is severe; combination therapy with rehabilitation could improve motor function. Here, we aimed to analyze the characteristics of adipose-derived MSCs (AD-MSCs) and determine their effectiveness in severe spinal cord injury (SCI) treatment. A severe SCI model was created and motor function were compared. The rats were divided into AD-MSC-transplanted treadmill exercise-combined (AD-Ex), AD-MSC-transplanted non-exercise (AD-noEx), PBS-injected exercise (PBS-Ex), and no PBS-injected exercise (PBS-noEx) groups. In cultured cell experiments, AD-MSCs were subjected to oxidative stress, and the effects on the extracellular secretion of AD-MSCs were investigated using multiplex flow cytometry. We assessed angiogenesis and macrophage accumulation in the acute phase. Spinal cavity or scar size and axonal preservation were assessed histologically in the subacute phase. Significant motor function improvement was observed in the AD-Ex group. Vascular endothelial growth factor and C-C motif chemokine 2 expression in AD-MSC culture supernatants increased under oxidative stress. Enhanced angiogenesis and decreased macrophage accumulation were observed at 2 weeks post-transplantation, whereas spinal cord cavity or scar size and axonal preservation were observed at 4 weeks. Overall, AD-MSC transplantation combined with treadmill exercise training improved motor function in severe SCI. AD-MSC transplantation promoted angiogenesis and neuroprotection.

Purpose: Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissues are rare mesenchymal neoplasms, some of which are malignant. However, their clinical and pathological characteristics remain unclear. This study was performed to investigate the clinical and pathological characteristics of PEComas in bone and soft tissues by leveraging information from the Japanese Musculoskeletal Oncology Group. Methods: Nine patients, including four male and five female patients with a median age of 50 years, were retrospectively reviewed. PEComas of the visceral organs, including the uterus and retroperitoneum, were excluded. Results: Eight tumors arose in the soft tissue and one in the bone, with a mean size of 8.8 cm. Four patients showed local recurrence or distant metastasis. The 1-year survival rate was 78%. Pathologically, eight tumors were classified as malignant and one as having uncertain malignancy potential. Half of the tumors showed high MIB-1 index values of > 30%. Immunohistochemically, the melanocyte marker HMB45 was expressed in 89% of the cases, and muscle-specific markers were expressed only in 30–50% of the cases. Transcription factor binding to IGHM enhancer 3 (TFE3) expression was positive in 100% of the patients. Tumors with high expression of TFE3 were classified as PEComas with malignant potential according to Folpe’s classification. Conclusions: Bone and soft tissue PEComas may have a higher malignancy potential than other visceral PEComas and are more likely to develop as TFE3-rearranged PEComas.

A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue. Diffuse TGCT (D-TGCT) most commonly develops in the knee, followed by the hip, ankle, elbow, and shoulder. Surgical removal is the only effective treatment option for the patients. However, a local recurrence rate as high as 47% has been reported. Recently, we revealed that zaltoprofen, a nonsteroidal anti-inflammatory drug possessing the ability to activate peroxisome proliferator-activated receptor gamma (PPARγ), can inhibit the proliferation of TGCT stromal cells via PPARγ. PPARγ is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. It plays an important role in the differentiation of adipocytes from precursor cells and exhibits antitumorigenic effects on certain malignancies. Therefore, we are conducting this investigator-initiated clinical trial to evaluate whether zaltoprofen is safe and effective for patients with D-TGCT or unresectable localized TGCT (L-TGCT). This study is a randomized, placebo-controlled, double-blind, multicenter trial to evaluate the safety and efficacy of zaltoprofen for patients with D-TGCT or L-TGCT. For the treatment group, zaltoprofen 480 mg/day will be administered for 48 weeks; the placebo group will receive similar dosages without zaltoprofen. Twenty participants in each group are needed in this trial (40 participants total). The primary outcome is the progression-free rate at 48 weeks after treatment administration. “Progression” is defined as any serious events (1. Repetitive joint swelling due to hemorrhage, 2. Joint range of motion limitation, 3. Invasion of adjacent cartilage or bone, 4. Severe joint space narrowing, 5. Increase in tumor size) requiring surgical interventions. We hypothesize that the zaltoprofen group will have a higher progression-free rate compared to that of the placebo group at 48 weeks. This is the first study to evaluate the efficacy of zaltoprofen in patients with D-TGCT or unresectable L-TGCT. We believe that the results of this trial will validate a novel treatment option, zaltoprofen, to stabilize disease progression for TGCT patients. University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( UMIN000025901 ) registered on 4/01/2017.

Introduction:Reconstruction using a total femur prosthesis (TFP) remains a challenging procedure in musculoskeletal tumor surgery. The purpose of this study was to show the clinical outcomes of total femur replacement (TFR) in our institute.Methods:Nine patients underwent reconstruction with a TFP after the wide resection of malignant bone and soft-tissue tumors of the femur between January 2003 and April 2014. The mean age of the patients at the time of TFR was 47.5 years, and the mean follow-up period was 52.9 months. The histological diagnoses were as follows: bone sarcoma (n = 4), soft-tissue sarcoma invading the femoral bones (n = 4), and metastatic bone tumor (n = 1).Results: The oncological outcomes were as follows: three patients achieved continuous disease free, two patients were alive with disease, and four patients died from disease. The 3- and 5-year overall survival rates were 88.9% and 55.6%, respectively. The rate of the overall survival in patients with primary bone tumors (100% at 5 years) was significantly better than that in patients with primary soft tissue sarcomas (0% at 5 years) (p = 0.015). A deep infection occurred postoperatively in one patient, but the patient was successfully treated with surgical debridement and revision surgery. There were no patients who showed dislocation or aseptic loosening. The mean Musculo-Skeletal Tumor Society functional score was 58.5% (46.7–80.0), with scores of 65.5% in patients with a primary bone tumor and 50.8% in those with a primary soft-tissue sarcoma.Discussion: In the present study, the patients who underwent TFR due to bone invasion by soft tissue sarcoma had a worse prognosis than the bone sarcoma patients.