In vivo study on the repair of rat Achilles tendon injury treated with non-thermal atmospheric-pressure helium microplasma jet.

Non-thermal atmospheric-pressure plasma (NTAPP) has been widely studied for clinical applications, e.g., disinfection, wound healing, cancer therapy, hemostasis, and bone regeneration. It is being revealed that the physical and chemical actions of plasma have enabled these clinical applications. Based on our previous report regarding plasma-stimulated bone regeneration, this study focused on Achilles tendon repair by NTAPP. This is the first study to reveal that exposure to NTAPP can accelerate Achilles tendon repair using a well-established Achilles tendon injury rat model. Histological evaluation using the Stoll's and histological scores showed a significant improvement at 2 and 4 weeks, with type I collagen content being substantial at the early time point of 2 weeks post-surgery. Notably, the replacement of type III collagen with type I collagen occurred more frequently in the plasma-treated groups at the early stage of repair. Tensile strength test results showed that the maximum breaking strength in the plasma-treated group at two weeks was significantly higher than that in the untreated group. Overall, our results indicate that a single event of NTAPP treatment during the surgery can contribute to an early recovery of an injured tendon.

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.

Impact of the COVID-19 pandemic on bone and soft tissue tumor treatment: A single-institution study.

OBJECTIVE: The spread of coronavirus disease 2019 (COVID-19) has caused a great deal of damage to daily medical care. We investigated the impact of the COVID-19 pandemic on bone and soft tissue tumor treatment at our hospital. METHODS: We conducted a retrospective comparative study of two groups of patients at Osaka City University Hospital during the period of increasing COVID-19 infections (February-December 2020, group C) and the same period the previous year (February- December 2019, group NC). Clinical data, including patient's age, gender, type of tumor, neoplasms, number of surgical cases for inpatients and outpatients, operation time, use of implants, length of hospital stay, inpatient hospital costs, number of inpatients receiving anticancer drugs, and postoperative complications in these two groups were retrospectively evaluated. RESULTS: The number of cases of malignant bone and soft tissue tumors that were resected during hospitalization was predominantly higher in group C than in group NC (P = 0.01). There were no significant differences in operation time, use of implants, and postoperative complications between group C and group NC, but there were significant differences in the length of hospital stay and hospital costs (P<0.001). CONCLUSIONS: The COVID-19 pandemic has been recognized throughout the world to have adverse effects in a variety of areas. It had a negative impact on hospital costs and the length of hospital stay in the field of bone and soft tissue tumor treatment.

High tartrate-resistant acid phosphatase (TRACP 5b) level in cystic fluid is a significant prognostic marker for postoperative recurrence in solitary bone cysts.

Purpose: The pathogenesis of cystic fluid storage in solitary bone cysts remains unclear. We aimed to compare the results of the biochemical analysis of cystic fluid with clinical findings. We identified a significant marker of postoperative recurrence. Methods: Twenty-seven male and eight female patients were studied; the median age at diagnosis was 11 (5-23) years. The mean follow-up period was 60 months (range: 14-146 months). Clinical information including sex, age, affected site, radiological findings of phase (active or latent), surgical procedure, outcome, and biochemical analysis of serum and cystic fluid was obtained. Results: The 5-year healing rate was 64.0%. Biochemical analysis revealed that total protein and albumin values in the cystic fluid were significantly lower, compared to those in the serum. Levels of bone turnover markers, such as alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b were remarkably elevated in the cystic fluid than in the serum. R values were 0.127, 0.076, and 0.095 for alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b, respectively. Areas under the receiver operating characteristic curves, calculated to assess the association of alkaline phosphatase, bone-specific alkaline phosphatase, and tartrate-resistant acid phosphatase 5b levels in the cystic fluid with postoperative recurrence, were 0.57, 0.51, and 0.70, respectively. Conclusions: No clear correlation of bone turnover marker levels between the serum and cystic fluid was observed. The high tartrate-resistant acid phosphatase 5b level in the cystic fluid was associated with postoperative recurrence. The bone resorption caused by osteoclasts is considered to affect postoperative recurrence. Level of evidence: Level IV.

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.

Tumor-skin invasion is a reliable risk factor for poor prognosis in superficial soft tissue sarcomas.

INTRODUCTION: Superficial soft tissue sarcomas are often left untreated unless they invade the skin and skin ulcers manifest. Progressive sarcomas frequently result in dismal oncological outcomes despite multidisciplinary treatment. This study aimed to identify prognostic factors for superficial soft tissue sarcomas. MATERIALS AND METHODS: This study retrospectively analyzed the clinicopathological data of 82 patients with superficial soft tissue sarcomas treated between August 2003 and December 2020 at our institution. A superficial soft tissue sarcoma was defined if the percentage of the area occupied by the tumor in the assessed region (skin, subcutaneous) was more than 50%. Age, sex, location, tumor size, tumor-skin invasion, tumor grade, and distant metastasis at initial diagnosis were evaluated as potential prognostic factors. Cox proportional hazards regression models were used to identify the prognostic factors. Five-year survival rates were assessed by the Kaplan-Meier method. RESULTS: The mean follow-up time was 60.1 months. The 5-year overall survival, 5-year local recurrence-free survival, and 5-year metastasis survival rates were 76.4%, 60.6%, and 71.0%, respectively. Univariate analysis showed significant relationships between poor prognosis and tumor size ≥5 cm, distant metastasis at initial diagnosis, and tumor-skin invasion. In the multivariate analysis, only the tumor-skin invasion was associated with worse overall survival. CONCLUSIONS: Superficial soft tissue sarcomas have biologically been considered a separate category due to their better prognosis. In this study, the tumor-skin invasion was the only significant factor associated with a poor prognosis. Therefore, all superficial soft tissue sarcomas without tumor-skin invasion should be treated as early as possible.

Does Systemic Chemotherapy Influence Skeletal Growth of Young Osteosarcoma Patients as a Treatment-Related Late Adverse Effect?

The aim of this study was to investigate the influence of systemic chemotherapy on the skeletal growth of young osteosarcoma patients as a treatment-related late adverse effect. We reviewed the height data of 20 osteosarcoma patients (13 males and 7 females) aged ≤18 years. The average (±SD) age at diagnosis was 14.5 (±3.3) years. The average follow-up interval was 89.6 months. After wide resection of the affected bones, reconstruction with tumor prostheses and auto-bone grafting was carried out in 11 and 9 cases, respectively. Pearson's correlation coefficient was calculated to evaluate the association between actual and predicted (using Paley's multiplier method) heights. Z-scores were used to compare the initial and final heights with the Japanese national growth curve. Actual and predicted heights were correlated according to Pearson's correlation coefficient (R = 0.503). Z-analysis showed that statistical significance (p = 0.04) was noted for the height data Z-scores of patients between ≤10 years and >10 years at the final follow-up. Systemic chemotherapy did not reduce skeletal growth in young osteosarcoma patients as a late adverse effect based on two different evaluation methods. However, patients aged ≤10 years at diagnosis may develop a short stature after systemic chemotherapy.

Outcomes of Sarcopenia Treatment for Malignant Bone and Soft Tissue Tumors in Elderly Patients.

Background/Aim: We determined the impact of sarcopenia on the treatment outcomes of malignant bone and soft tissue tumors in elderly patients. Patients and Methods: We retrospectively reviewed 76 patients (age ≥65 years) who were treated for malignant bone and soft tissue tumors. Sarcopenia was assessed by measuring the cross-sectional area of the psoas muscles at the L3 vertebra from preoperative computed tomography images and categorized using the total psoas area/m 2 (TPA/m 2 ) ≤5.0 cm 2 /m 2 . The patients' clinical data were then evaluated. Results: The operation time, length of hospital stay, and median overall survival were not different between the sarcopenia (n=41) and no-sarcopenia (n=35) groups. The local recurrence rate (p=0.01) and incidence of postoperative complications (p=0.02) significantly differed between both groups. The TPA/m 2  of both groups significantly decreased at the final follow-up. Conclusion: Sarcopenia negatively influenced wound healing and local recurrence, and was significantly exacerbated postoperatively in all elderly patients.

An analysis of tumor-related skin temperature differences in malignant soft-tissue tumors.

BACKGROUND: Soft tissue tumors are often accompanied with elevated skin temperature; however, studies concerning the relationship between soft-tissue tumors and skin temperature elevation are scarce. We aimed to evaluate the clinical significance of skin temperature elevation in soft-tissue tumors and identify factors related to skin temperature elevation. PATIENTS AND METHODS: This study comprised 118 patients at our hospital with soft-tissue tumors, excluding lipomatous tumors, whose pathological diagnosis was surgically confirmed between February 2017 and March 2021. Sixty-one and 57 patients had been diagnosed with benign lesions and malignant tumors, respectively (men, 64; women, 54; median age, 61 [range, 20-92] years). The relationship between skin temperature, monitored using a thermography camera, and the presence of soft-tissue malignancy was investigated. We reviewed clinical data to identify factors related to elevated skin temperature. RESULTS: Temperature differences ≥ 0.2 °C compared to the unaffected side were significantly associated with the presence of malignant tumors (p < 0.001). Logistic regression analysis indicated that intertumoral blood supply was associated with elevated skin temperature (OR 3.22, 95% CI 2.03-5.13; p < 0.001). CONCLUSIONS: Elevated skin temperature, influenced by intertumoral blood supply, may be an important adjunct to physical findings when diagnosing malignant soft-tissue tumors. CLINICAL RELEVANCE: Intertumoral blood supply influenced elevated skin temperature in malignant soft-tissue tumors. A skin temperature difference ≥ 0.2 °C compared to the unaffected side can help differentiate between benign and malignant tumors. Skin temperature differences may help in diagnosing malignant soft-tissue tumors.

An unusual presentation of pneumothorax associated with cystic lung metastasis from epithelioid sarcoma: A case report and review of the literature.

Circumscribed solid nodules are common in pulmonary metastases from sarcoma, but cystic pulmonary metastases from sarcomas are extremely rare. An unusual case of a 33-year-old man presenting with left spontaneous pneumothorax in association with cystic pulmonary metastases from an epithelioid sarcoma in the left forearm was discussed in the present study. The patient underwent wide resection of an epithelioid sarcoma in the left forearm 6 years prior. Periodical computed tomography revealed a gradual increase in the number and size of bilateral multiple cystic pulmonary metastases despite repeated chemotherapy treatment. At 33 years of age, the patient visited the outpatient department for sudden left chest pain and dyspnea. Plain radiography demonstrated spontaneous pneumothorax in the left lung; chest tube insertion and pleurodesis were successfully performed thereafter. At the last follow-up, 24 months after spontaneous pneumothorax, he is still alive and receiving chemotherapy treatment. Spontaneous pneumothorax is a common complication associated with cystic pulmonary metastases from epithelioid sarcoma. Orthopedic oncologists need to be aware of this unusual sarcomatous metastasis during the follow-up of advanced epithelioid sarcoma.

Clinical features of soft tissue sarcoma presenting intra-tumour haematoma: case series and review of the literature.

INTRODUCTION: Intra-tumour haematoma is an uncommon clinical presentation in malignant soft tissue tumours. This study aimed to highlight the clinical features of patients with soft tissue sarcomas with intra-tumour haematoma. METHODS: The patient group was composed of eight men and one woman aged between 29 and 83 years (mean 44.0 ± 20.8). The average follow-up was 29.8 months. Clinical information, including clinical features, radiological information and treatment course, was retrospectively investigated. RESULTS: Tumours were predominantly located in the chest wall and thigh, and average diameter was 10.3 cm. Six patients underwent needle biopsy with ultrasound sonography, and three underwent an open biopsy. Histological diagnoses indicated that all tumours were high grade, three of which were undifferentiated pleomorphic sarcomas, three synovial sarcomas, two pleomorphic liposarcomas, one a leiomyosarcoma and one a malignant peripheral nerve sheath tumour. The median diagnostic delay time was 3.0 months. Magnetic resonance imaging (MRI) indicated a haematoma area <25 % in three, 25-50 % in four and 50 % two. A wide resection was performed in eight patients, and radiotherapy was administered to one patient for the initial local treatment of a primary tumour. Local recurrence was detected in four patients, whilst five developed lung metastases. The five-year survival rate was 57.1 % and median survival 34.0 months. CONCLUSIONS: Soft tissue sarcomas with intra-tumour haematoma presented with locally aggressive and highly metastatic behavior, consistent with high-grade tumours.