Background: The Hedgehog signaling pathway functions as an organizer in embryonic development. Recent studies have demonstrated constitutive activation of Hedgehog pathway in various types of malignancies. However, it remains unclear how Hedgehog pathway is involved in the pathogenesis of osteosarcoma. To explore the involvement of aberrant Hedgehog pathway in the pathogenesis of osteosarcoma, we investigated the expression and activation of Hedgehog pathway in osteosarcoma and examined the effect of SMOOTHENED (SMO) inhibition. Results: To evaluate the expression of genes of Hedgehog pathway, we performed real-time PCR and immunohistochemistry using osteosarcoma cell lines and osteosarcoma biopsy specimens. To evaluate the effect of SMO inhibition, we did cell viability, colony formation, cell cycle in vitro and xenograft model in vivo. Real-time PCR revealed that osteosarcoma cell lines over-expressed Sonic hedgehog, Indian hedgehog, PTCH1, SMO, and GLI. Real-time PCR revealed over-expression of SMO, PTCH1, and GLI2 in osteosarcoma biopsy specimens. These findings showed that Hedgehog pathway is activated in osteosarcomas. Inhibition of SMO by cyclopamine, a specific inhibitor of SMO, slowed the growth of osteosarcoma in vitro. Cell cycle analysis revealed that cyclopamine promoted G1 arrest. Cyclopamine reduced the expression of accelerators of the cell cycle including cyclin D1, cyclin E1, SKP2, and pRb. On the other hand, p21^cip1 wprotein was up-regulated by cyclopamine treatment. In addition, knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo. Conclusions: These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma.

Well-differentiated liposarcoma (WDL)/atypical lipomatous tumor (ALT) is considered a low-grade malignancy that rarely metastasizes but should be carefully followed because recurrence or dedifferentiation may occur. It is recognized that WDL and ALT are essentially synonymous, describing lesions that are identical both morphologically and karyotypically, and that site-specific variations in behavior relate only to surgical resectability. Preoperative differential diagnosis between lipoma and ALT has been well studied because their clinical and image characteristics are very similar. We evaluated the factors that may differentiate ALTs from lipomas, and validated a tentative scoring system for the diagnosis of the 2 tumor types. Forty-eight lipomas and 12 ALTs were included. The mean age, location and depth of the tumor as well as the compartment were not significantly different between the 2 groups. To evaluate the vascularity of the tumors, the average number of intratumoral vessels on pathological sections was calculated and compared between cases of lipoma and ALT. The tumor size was significantly larger in ALT cases than in lipoma cases (P < 0.001). Magnetic resonance imaging (MRI) revealed septal structures in 91.6% of ALTs, whereas 20.8% of lipomas showed septa. Contrast enhancement in MRI was found significantly more often in ALTs (81.2%) than in lipomas (18.8%) (P < 0.001). We created a “ALT score” to discriminate between lipoma and ALT (0–6 points). ALT cases gave significantly higher point values (average 5.1 points) than lipoma cases (average 1.7 points) (P < 0.001). We found a significantly increased number of vessels in cases of ALT than in cases of lipoma (P = 0.001). Our ALT score may help surgeons to differentiate a suspected ALT from a lipoma and could recommend a marginal resection in cases of suspected ALT. Increased intratumoral vascularity in ALT is reflected in the MRI findings and may play a key role in the acquisition of a malignant phenotype in adipocytic tumors.

Malignant soft-tissue sarcoma resection is associated with a relatively high incidence of surgical site infection (SSI). The known risk factors for SSI following soft-tissue sarcoma resection include tumor size and location, prolonged surgery, and massive blood loss. The geriatric nutritional risk index (GNRI) was used as a tool to help predict the occurrence of SSI after major surgery. We investigated the utility of the GNRI as a predictor of SSI following soft-tissue sarcoma resection. We retrospectively reviewed 152 patients who underwent surgical resection of soft-tissue sarcoma in our institute, and found that the incidence of SSI was 18.4% (28/152). The SSI and non-SSI groups significantly differed regarding surgical time, diameter of the skin incision, maximum tumor diameter, instrumentation, presence of an open wound, preoperative chemotherapy, preoperative C-reactive protein concentration, and GNRI. Binomial logistic regression analysis showed that the risk factors for SSI following soft-tissue sarcoma surgery were male sex, larger skin incision diameter, larger maximum tumor diameter, presence of an open wound, and lower GNRI. Our findings indicate that malnutrition is a risk factor for SSI after soft-tissue sarcoma resection, and suggest that appropriate assessment and intervention for malnutrition may reduce the incidence of SSI.

Predicting outcomes in patients with soft tissue sarcoma (STS) is challenging. To improve these predictions, we retrospectively analyzed common nutritional assessment systems, including Glasgow prognostic score (GPS), Geriatric Nutritional Risk Index (GNRI), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), and controlling nutritional (CONUT) score against outcomes in 103 patients with STS, of whom 15 (14.6%) died within 1 year of diagnosis. GPS, GNRI, NLR, PLR, and CONUT scores significantly differed between patients who died within one year and patients who lived longer. Binomial logistic regression analysis showed that male sex, older age at diagnosis, higher GPS, higher stage, and unresectable STS were risk factors for death within a year of diagnosis. Overall survival was evaluated by Cox proportional hazards models, which correlated higher NLR, higher PLR, larger maximum diameter of tumor, higher stage, and unresectable STS with poor prognosis. We next examined prognostic factors in the 93 patients with resectable STS, and found male sex, higher GPS, and higher stage were correlated with poor prognosis in these patients. Our findings suggest that GPS, NLR, and PLR are simple predictors of outcome in patients with STS. Nutritional therapies might improve their GPS and prognosis.

Most bone tumors that occur in the clavicle are malignant. A few giant cell tumors (GCTs) of the clavicle have been reported; however, the most appropriate operative method for this tumor has never been discussed. A 54-year-old man noticed enlargement of the proximal aspect of the right clavicle. A plain X-ray revealed lytic change and ballooning of the proximal end of the right clavicle. The tumor was isointense on T1-weighted magnetic resonance images and showed a mixture of low- and high-intensity areas on T2-weighted images without extension to the surrounding soft tissues. Bone scintigraphy showed strong accumulation (normal/tumor ratio, 2.31), and positron emission tomography revealed strong uptake of fluorine-18-2-fluoro-2-deoxy-d-glucose (SUVmax, 6.0) in the proximal part of the right clavicle. Because we could not completely exclude malignancy, an open biopsy was performed. Pathologically, the tumor comprised mononuclear stromal cells and multinuclear giant cells, resulting in a diagnosis of a GCT of the bone. Although curettage may be considered for such lesions (Campanacci grade II), we chose resection to minimize the chance of recurrence. The tumor was resected en-bloc with the proximal half of the clavicle. No postoperative shoulder disproportion was observed, and full range of motion of the right shoulder was maintained. The patient was satisfied with the surgical outcome (Musculoskeletal Tumor Society score of 96 %). He returned to his original job as a land and house investigator without any signs of recurrence for 1 year after surgery. Although GCT of the bone rarely occurs in the clavicle, the typical X-ray findings demonstrated in the present case are helpful for a correct diagnosis. Although en-bloc resection without reconstruction is appropriate for GCTs in expendable bones, there has been much discussion about shoulder function after total claviculectomy. Considering the importance of the function of the clavicle, which is to support the scapula through the acromioclavicular joint, we preserved the muscle attachments of the deltoid, trapezius, and pectoralis major. Because both the oncological and functional outcomes were satisfactory, we recommend preservation of as much of the clavicle as possible in patients with clavicular bone tumors.

PURPOSE: The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING: The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. METHODS: Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. RESULTS: The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). CONCLUSION: Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.