Management of Soft-tissue Tumors With a Size of 2-5 cm, Including Malignancy.

BACKGROUND/AIM: The management of soft-tissue tumors of 2-5 cm is not specified. We investigated the management of these cases. PATIENTS AND METHODS: Among 105 cases with soft-tissue tumors from 2014 to 2021, 38 with tumors of 2-5 cm were retrospectively reviewed. The clinical characteristics, diagnosis, and management were investigated. RESULTS: The study population included 14 males and 24 females (mean age=57 years). Common histological diagnoses included lipoma, epidermal cyst, and hemangioma as benign tumors, and leiomyosarcoma (n=2) and metastatic soft-tissue carcinoma (n=1) as malignant tumors. Magnetic resonance imaging, needle and excisional biopsy were performed in 35, 19 and 19 cases, respectively. The mean follow-up period was 7 months. No recurrence was observed. CONCLUSION: Malignancy exists, even in soft-tissue tumors of 2-5 cm (3/38; 8%). To avoid unplanned excision, needle biopsy should be considered for cases with magnetic resonance imaging abnormalities.

Low-grade myofibroblastic sarcoma of the levator scapulae muscle: a case report and literature review.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is described as a distinct atypical myofibroblastic tumor often with fibromatosis-like features and predilection for the head and neck, especially the oral cavity and larynx. LGMS arising in the levator scapulae muscle is extremely rare. CASE PRESENTATION: A 69-year-old woman was admitted to our hospital because she noticed a hard mass in her left neck six months prior. Magnetic resonance images (MRI) showed a soft tissue tumor of the left levator scapulae muscle. A core needle biopsy showed cellular fascicles or a storiform growth pattern of spindle-shaped tumor cells with minimally atypia. Immunohistochemistry revealed focally positive for α-smooth muscle actin (α-SMA), negative for S-100, and a low-grade spindle cell sarcoma was suspected. Following a biopsy, the tumor was resected with a wide surgical margin. Immunohistochemical staining was a positive for vimentin and α-SMA and negative for desmin, CD34, nuclear ß-catenin, and h-caldesmon. LGMS diagnosis was determined based on the histopathological findings. The patient was alive with no evidence of disease eight years after the surgery. CONCLUSIONS: To the best of our knowledge, this is the first case report of LGMS arising in the levator scapulae muscle. In addition to the case report, 48 reports with 103 LGMS cases are reviewed and discussed. In previous reports of LGMS, there were 43 females and 60 males, with a mean age of 43.0 years (range, 2-75). There were 13 (12.6%) patients aged < 18 years, 67 (65.1%) patients aged 18 to 59 years, and 23 (22.3%) patients aged ≥60 years. The average tumor size was 4.4 cm (range: 0.4-22.0). The commonest sites of LGMS was the tongue. Tumor growth patterns were evaluated in 52 cases, and 44 cases (84.6%) showed infiltrative growth patterns. Local recurrence was 26.7%, and distant metastasis was 4.4%. Because of the locally aggressive feature, it is important to diagnose LGMS with biopsy and to excise the tumor with an adequately wide margin.

Treatment strategy for atypical ulnar fracture due to severely suppressed bone turnover caused by long-term bisphosphonate therapy: a case report and literature review.

BACKGROUND: Atypical fractures may occur due to the combined effect of severely suppressed bone turnover (SSBT) caused by long-term bisphosphonate treatment and chronic repetitive bone microdamage. Atypical fracture of the ulna due to SSBT is a rare entity; there is no standardized treatment strategy for this condition. We successfully treated a patient with atypical fracture of the ulna. Herein, we present this patient, review the relevant literature, and discuss the treatment strategy. CASE PRESENTATION: An 84-year-old woman presented with atypical fracture of the left ulnar shaft due to SSBT. She had a history of bisphosphonate therapy (ibandronate and alendronate) since more than 10 years; her bone turnover was severely suppressed. We performed open reduction and internal fixation (ORIF) using dual plate with some additional treatments. These included drilling and decortication, use of autogenous bone graft, low-intensity pulsed ultrasound (LIPUS) treatment, and administration of teriparatide. Finally, bone union was observed at 11 months after surgery. CONCLUSIONS: Based on the literature review and our experience with this case, ORIF alone may not be adequate to achieve bone union; drilling, decortication, and use of cancellus bone graft is important to achieve favorable outcomes. Administration of teriparatide and LIPUS may facilitate early bone union, although further studies are required to provide more definitive evidence. Furthermore, ORIF using dual plate may help avoid implant failure owing to the long time required for bone union.

Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression.

Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti-inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ-responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity.

Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen.

PURPOSE: To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma. METHODS: Between 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy. RESULTS: Among the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone. CONCLUSIONS: Joint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma.

Efficacy of glycogen synthase kinase-3ß targeting against osteosarcoma via activation of ß-catenin.

Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3ß (GSK- 3ß) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3ß inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3ß in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3ß inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of ß-catenin in osteosarcoma cells following GSK-3ß inhibition. Expression of the active form of GSK- 3ß (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3ß activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3ß-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3ß reduced phosphorylation at GSK- 3ß-phospho-acceptor sites in ß-catenin and increased ß-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3ß inhibitors is associated with activation of ß-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3ß in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma.

Prediction of skeletal-related events in patients with non-small cell lung cancer.

PURPOSE: Advanced lung cancer frequently causes bone metastasis which can be associated with skeletal-related events (SREs) that may cause significant deterioration of the patient's quality of life (QoL). The Spinal Instability Neoplastic Score (SINS) can be used to assist in standardizing evaluations of neoplastic spinal instability between spinal and non-spine surgeons. This research investigated the association between SREs and SINS for patients with non-small cell lung cancer (NSCLC). METHODS: Between 2009 and 2013, 47 patients with NSCLC who were diagnosed with bone metastasis were classified using SINS into either a stable group (SINS, 0-6 points) or unstable group (SINS, 7-18 points). The primary endpoint was time from diagnosis of metastasis to SREs. Secondary endpoints included tumor type and epidermal growth factor receptor (EGFR) mutational status. SREs were defined as spinal compression, pathologic fracture, spinal surgery, and hypercalcemia. RESULTS: Patients included 37 cases of adenocarcinoma and 10 cases of squamous cell carcinoma. Mean follow-up time was 10.2 ± 13.7 months. SRE incidence was 15.0 % (3/20) in the stable group versus 44.4 % (12/27) in the unstable group (p = 0.048). A Cox regression model revealed that an EGFR-positive mutational status (hazard ratio [HR] = 0.15, 95 % CI, 0.030.71; p = 0.017) or good spinal stability (HR = 0.49; 0.08-0.99; p = 0.049) were favorable prognostic factors. CONCLUSION: The incidence of SREs was significantly lower in NSCLC patients with better spinal stability as determined by SINS, which was a good prediction tool for SREs from bone metastasis. The lower incidence of SREs in EGFR-positive patients suggests tumor biology should be considered when predicting SREs.

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV.

Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities.

BACKGROUND: Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. METHODS: The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). RESULTS: Final bone union occurred in 11 patients in the FFP group (84.6%) and in 7 patients in the PFP group (100%). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. CONCLUSIONS: The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP.

Late recurrence of osteosarcoma: a report of two cases.

We report 2 cases of late recurrence of osteosarcoma after 6 and 7 years. One patient had pulmonary metastasis, and the other had soft tissue recurrence. Both patients underwent complete resection and chemotherapy. The first patient achieved complete remission and remained disease-free 47 months later and had no limitation in his daily life. The second patient had a re-recurrence and underwent further resection and chemotherapy. He remained disease-free 35 months later and could walk using a T-handled walking cane.

Treatment strategies for well-differentiated liposarcomas and therapeutic outcomes.

This study examined 45 patients with well-differentiated liposarcoma who were surgically treated at our hospital (initial surgery in 41 patients and reoperation in 4). Only one patient had recurrence among patients who underwent initial surgery, and the recurrence was localised in the retroperitoneal space. For patients who underwent reoperation, the mean time between the initial surgery and the recurrence was 16.5 years. None of the 45 patients developed distant metastasis. It is important to preserve not only neurovascular bundles but also lower limb muscles in order to maintain ambulatory ability in the elderly patients. For well-differentiated liposarcomas of the limbs, it is important to establish a surgical margin beyond the marginal resection border and to perform muscle resection to the extent that would not greatly reduce the muscle strength.