Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma.

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures.

Optimal Prognostic Factors for Metastatic and Inoperable Sarcomas Treated With Pazopanib, Eribulin, and Trabectedin.

BACKGROUND/AIM: The prognosis of metastatic and inoperable sarcomas is extremely poor, and intensive chemotherapy-based treatment is typically administered to prolong survival. Currently, pazopanib, eribulin, and trabectedin are key drugs used in patients with these sarcomas. The aim of the study was to identify prognostic factors for metastatic and inoperable bone and soft tissue sarcomas. PATIENTS AND METHODS: Clinicopathological data of 46 patients with metastatic and inoperable sarcomas treated with pazopanib, eribulin, and trabectedin between January 2013 and February 2022 at our institution were retrospectively analyzed. Age, sex, primary tumor location, adverse effects, history of doxorubicin and radiation therapy, performance status scores, maximum tumor response, and survival duration were evaluated. The significant prognostic factors were identified using Cox proportional hazards models. Moreover, the 5-year survival rate was evaluated using the Kaplan-Meier method. RESULTS: The median survival duration after treatment was 13.3 months, where the 5-year overall survival rate was estimated to be 9.85%. Both univariate and multivariate analyses revealed significant relationships among patient prognosis, performance status, and tumor response. CONCLUSION: Performance status scores and tumor response were significantly associated with patient prognosis. Therefore, regardless of age, sex, primary tumor location, adverse effects, and history of doxorubicin and radiation therapy, use of cutting-edge drugs, such as pazopanib, eribulin, and trabectedin, may be advantageous in patients with advanced sarcomas, if their drug response and performance status scores are good.

Anti-Tumor Effect and Neurotoxicity of Ethanol Adjuvant Therapy after Surgery of a Soft Tissue Sarcoma.

Wide resection is the main treatment for sarcomas; however, when they are located near major nerves, their sacrifices might affect limb function. The efficacy of ethanol adjuvant therapy for sarcomas has not been established. In this study, the anti-tumor effect of ethanol, as well as its neurotoxicity, were assessed. In vitro anti-tumor effect of ethanol as evaluated using MTT, wound healing, and invasion assays on a synovial sarcoma cell line (HS-SY-II). In vivo, an assessment was conducted in nude mice (implanted with subcutaneous HS-SY-II) treated with different ethanol concentrations after surgery with a close margin. Sciatic nerve neurotoxicity was assessed with electrophysiological and histological examination. In vitro, ethanol concentrations at 30% and higher showed cytotoxic effects in MTT assay and markedly reduced migration and invasive ability of HS-SY-II. In vivo, both 30% and 99.5% ethanol concentrations, compared to 0% concentration, significantly reduced the local recurrence. However, in the group treated with 99.5% ethanol, nerve conduction tests showed prolonged latency and decreased amplitude, and morphological changes suggestive of nerve degeneration were observed in the sciatic nerve, while the 30% ethanol did not cause neurological damage. In conclusion, 30% is the optimal concentration for ethanol adjuvant therapy after close-margin surgery for sarcoma.

Review of the referral documents of patients with malignant soft tissue tumors.

Fifteen years have passed since the soft tissue tumor practice guidelines were first published in Japan. Tumor size of ≥ 5 cm and tumor depth were key findings suggestive of malignant soft tissue tumors. We reviewed the referral documents provided by the referring physicians to see if these two findings were reported. The study was conducted from January 2007 to December 2021 and included 142 patients (83 men and 59 women; median age, 64 [6-94] years) with malignant soft tissue tumors. Patient referral documents from physicians were screened for descriptions of the tumor size and depth. The tumor size, depth, and both were described in 51.4%, 36.6%, and 23.2% of the referrals, respectively. Both findings were mentioned in 23.8%, 21.7%, and 25.0% of referrals in 2007-2011, 2012-2016, and 2017-2021, respectively. Of orthopedic surgeons and other physicians, 61.2% and 38.6%, respectively, described the tumor size. Whether the general physicians could follow the soft tissue tumor practice guidelines was difficult to conclude by reviewing patient referral documents. However, orthopedic surgeons seemed to pay more attention to tumor size. Awareness regarding soft tissue tumor practice guidelines should be increased to help diagnose malignant soft tissue tumors early.

Prediction of the future leg length after rotationplasty in a 3-year-old boy with extraskeletal Ewing sarcoma and long follow-up until skeletal maturity: a case report.

Rotationplasty is a useful option for limb salvage surgery in pediatric patients with malignant bone and soft tissue tumors. However, bone growth after rotationplasty remains poorly characterized. We present a case of a 3-year-old boy with extraskeletal Ewing sarcoma who underwent multidrug chemotherapy (vincristine, doxorubicin, ifosfamide and etoposide), wide resection and functional reconstruction with rotationplasty. No radiotherapy was administered during the treatment course and the patient has been followed up for 16 years after rotationplasty. Leg length at skeletal maturity was predicted using postoperative radiograph measurements of the affected leg at the age of 4 years. Two conventional prediction methods, the multiplier and straight-line graph methods were used for prediction. The predicted leg length was compared with the actual leg length to assess bone growth after rotationplasty. Immediately after surgery, the lengths of the affected lower leg, femur and tibia were 32.5, 15.0 and 17.6 cm, respectively, and the predicted leg length of the affected leg at skeletal maturity using the multiplier and straight-line graph methods was 44.6 and 44.2 cm, respectively. However, the actual length of the affected leg at skeletal maturity was 49.8 cm, and the gap between actual and predicted lengths was more than 5 cm. In conclusion, the affected leg after rotationplasty showed more than expected bone overgrowth compared with the predictions of the conventional methods.

Prognostic value of psoas major muscle density in patients with breast cancer metastases to bone: a retrospective single-center cohort study.

OBJECTIVE: Although sarcopenia is associated with poor prognosis for cancer patients, the relationship between muscle quantity and quality, and prognosis of breast cancer patients with bone metastases is unclear. This study aims to evaluate the association of muscle parameters, muscle area and density, and overall survival (OS) from the diagnosis of bone metastases in breast cancer patients with bone metastases. METHODS: This study retrospectively investigated the prognostic value of muscle area and density in 90 women who were diagnosed with breast cancer with bone metastases between September 2005 and June 2018. We measured psoas major muscle and paravertebral muscle area and density on single axial computed tomography images at the L3 level and subgrouped the patients into higher or lower groups for each muscle measurement, using median values as cutoffs. We evaluated associations between OS and muscle parameters, using a Cox proportional hazards model adjusted by age and prognostic score for bone metastases (modified Katagiri score). RESULTS: Median OS among patients with lower psoas major muscle density (25 months) was significantly shorter than in the higher psoas major muscle density group (61 months; hazard ratio: 1.79, 95% confidence interval: 1.01-3.16, P = 0.045). However, muscle area and paravertebral muscle density were not associated with OS in this setting. CONCLUSION: Lower psoas major muscle density was a predictor of poor prognosis in patients with breast cancer metastases to bone. The association between psoas major muscle density and prognosis allows wider research into interventions that can prevent loss of muscle density.