No abstract

Programmed cell death-ligands 1 (PD-L1) is a key immune checkpoint protein and a promising therapeutic target for malignancy tumor immunotherapy. The prognostic value of PD-L1 in patients with bone and soft tissue sarcoma remains controversial. Therefore, this meta-analysis is conducted to evaluate the associations of PD-L1 expression with overall survival (OS), progression-free survival (PFS), and clinicopathological characteristics of sarcomaA comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library was conducted for relevant studies. A total of 14 studies published from 2013 to 2017 were included. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from included studies to assess the association between PD-L1 expression and OS, PFS of patients with sarcoma. Other relevant data were extracted to evaluate the correlations of PD-L1 expression with risk and clinicopathological characteristics of sarcoma. Stata 12.0 software was applied to calculate the strength of association between PD-L1 expression and sarcoma.In total, 14 articles containing 15 independent studies and 1,451 patients were included in this meta-analysis. We found that the high PD-L1 expression was associated with poorer overall survival (HR 1.27, 95% CI: 0.70–1.84 P = .000) and poorer events-free survival (HR 2.05, 95% CI: 1.55–2.70, P = .000) in bone and soft-tissue sarcoma patients. Additionally, we conducted subgroup analysis according to histology type, ethnicity, target of PD-L1 assessment, cutoff, the significant correlations with poor overall survival and events-free survival were also observed. In contrast none of the clinicopathological characteristics (gender, age, tumor site, tumor grade, tumor depth, tumor necrosis rate, metastasis, recurrence, chemotherapy, radiotherapy) was found to be associated with PD-L1 expression in our analysis.The findings from this meta-analysis indicate that PD-L1 expression might be a useful predicative factor of poor prognosis for patients with bone and soft tissue sarcoma.

BackgroundGorham-Stout disease, also known as vanishing bone disease, idiopathic massive osteolysis, is a rare entity of unknown etiopathology. This disease is characterized by destruction of osseous matrix and proliferation of lymphatic vascular structures and associated with massive regional osteolysis. It has a variable clinical presentation and is commonly considered as a benign disease with a progressive tendency and an unpredictable prognosis. The diagnosis is made by exclusion and based on combination with histological, radiological, and clinical features. Despite that several therapeutic options have shown certain efficacy, the effective treatment still remains controversial and there is no standard treatment to be recommended.Case presentationA previously healthy 40-year-old man presented with right lateral malleolus pain after an ankle sprain and was referred to our hospital. The radiographs indicated rapid massive bone destruction in the distal right lateral malleolus with an unclear margin. Based on the combination with histological, radiological, and clinical features, the diagnosis of Gorham-Stout disease was made. Considering that the residual function of malleolus had to be protected, prior bisphosphonate was used to control the progression of lesion, followed by surgical resection and biological reconstruction with autologous fibular bone grafting. The patient was followed up 8 years after surgery, he presented without progression and recurrence.ConclusionsWe depict a case of Gorham-Stout disease at the right lateral malleolus and was successfully controlled by medication and surgical intervention. Based on the prior effective medical treatment, resection with biological reconstruction is a useful approach to treat Graham-Stout disease in bone.

Osteosarcoma (OS) is rare cancer with bimodal age distribution with peaks observed in children and young adults. Typically, OS is treated with pre-surgery neoadjuvant therapy, surgical excision, and post-surgery chemotherapy. However, the efficacy of treatment on disease prognosis and objective response is not currently optimal, often resulting in drug resistance; in turn, highlighting the need to understand mechanisms driving resistance to therapy in OS patients. Using Doxycycline (Dox)-sensitive and resistant variants of OS cells lines KHOS and U2OS, we found that the resistant variants KHOS-DR and U2OS-DR have significantly higher in vitro proliferation. Treating the Dox-sensitive KHOS/U2OS cells with exosomes isolated from KHOS-DR/U2OS-DR made them resistant to treatment with Dox in vitro and in vivo and enhanced tumor growth and progression, while decreasing overall survival. Expression of the long non-coding RNA (lncRNA) ANCR was significantly higher in the KHOS-DR and U2OS-DR variants. SiRNA-mediated knockdown of ANCR decreased in vitro proliferation, while increasing sensitivity to Dox treatment in the KHOS-DR/U2OS-DR cells. Expression of the exosomal lncRNA ANCR was critical for drug resistance and OS tumor progression in xenografts and was correlated to resistance to Adriamycin and overall survival is patients with OS. These results establish lncRNA ANCR as a critical mediator of resistance to therapy in OS patients, highlighting it as a potential therapeutic target in OS patients.