Aberrantly expressed miRNAs play a crucial role in the development of multiple cancer types, including chordoma. However, the detailed molecular mechanisms are unclear and need to be elucidated. In this study, miRNAs were screened by miRNA array analysis and then confirmed by real-time PCR analysis. We found that miR-16-5p was significantly downregulated in chordoma, and overexpression of miR-16-5p suppressed chordoma cell proliferation, invasion and migration in vitro and in vivo and correlated with the upregulated expression of E-cadherin and downregulated expression of N-cadherin and vimentin. Furthermore, Smad3 was identified as a target of miR-16-5p, and Smad3 was highly expressed in chordoma tissues. Further research showed that knockdown of Smad3 had an effect similar to that of overexpression of miR-16-5p in chordoma cells. Our findings demonstrate that miR-16-5p plays a tumor suppressor role in chordoma progression by targeting Smad3, which could provide a promising prognostic and therapeutic strategy for chordoma treatment.

Background: Reconstruction with an endoprosthesis following pelvic tumor resection has increased over the years. However, the long-term results reflect a disappointing frequency of mechanical complications and failures. In an attempt to enhance implant fixation, an electron beam melting (EBM)-based modular hemipelvic endoprosthesis was introduced. Our aim was to explore the preliminary clinical outcomes for patients who have been managed with this prosthesis. Methods: We reviewed the records of 80 consecutive patients who had been managed at a single center between June 2015 and September 2017. Chondrosarcoma was the predominant diagnosis (31.3%). Osseous metastases were diagnosed in 16 patients (20.0%). The position of the reconstructed metallic acetabulum was measured on an anteroposterior pelvic radiograph. Bone ingrowth was evaluated in 2 samples harvested from patients with tumor recurrence. Results: After a median duration of follow-up of 32.5 months (range, 9 to 52 months), no acetabular component instability was detected on radiographs. Histological sectioning of specimens harvested from 2 patients with tumor recurrence showed bone trabeculae extending toward the implant and bone ingrowth within the porous network. At the time of the latest follow-up, 59 patients (73.8%) were alive with no evidence of disease, 5 patients (6.3%) were alive with disease, and 16 patients (20.0%) had died of disease. Local recurrence occurred in 9 patients (11.3%). The mean Musculoskeletal Tumor Society score at the time of the latest follow-up was 83.9% (range, 43% to 100%). Complications occurred in 16 patients (20%), with wound dehiscence being the most common complication (8 patients; 10%). No aseptic loosening was found. Five patients (6.3%) had deep infection, and 2 patients (2.5%) had dislocation. Conclusions: The use of a 3-dimensional (3D)-printed modular hemipelvic endoprosthesis with a highly porous metal interface represents a potential choice as a pelvic endoprosthesis after internal hemipelvectomy for the treatment of a primary or metastatic tumor. These preliminary results demonstrate stable fixation with acceptable early functional and radiographic outcomes. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets. Methods Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC). Results The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo. Conclusions Our study implicates that the CCL5–CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5–CCR5 axis is a potential therapeutic target in chordoma.

Purpose: It is difficult to predict prognosis of patients with osteosarcoma at initial diagnosis due to lack of efficient prognostic parameters. We evaluated the relationship between level of circulating serum exosomal PD-L1 (Sr-exosomal PD-L1) at initial diagnosis and oncologic outcome during the follow-up. Experimental Design: Sixty-seven patients with newly diagnosed osteosarcoma were prospectively recruited. Fasting blood was collected and exosome isolation was performed using ultracentrifugation method. Evaluation of Sr-exosomal PD-L1 was performed respectively by immunogold labeling and ELISA method. Correlation between level of Sr-exosomal PD-L1 at initial diagnosis and clinical risk factors was assessed. Results: Mean follow-up was 46.7 months. Two-year and 5-year overall survival (OS) rates were respectively 96.9% and 62.5%. Two-year and 5-year disease-free survival (DFS) rates were respectively 85.0% and 31.4%. Results revealed a significantly positive association between high PD-L1 cargo of circulating exosomes and clinicopathologic disease markers such as pulmonary metastasis, multiple metastasis, and death. Patients who died of disease at final follow-up had higher level of Sr-exosomal PD-L1 at initial diagnosis, which compared with patients who were still alive at last follow-up. Patients in group of ≥14.23 pg/mL Sr-exosomal PD-L1 at initial diagnosis had inferior DFS compared with patients in group of <14.23 pg/mL at initial diagnosis. Patients in group of ≥25.96 pg/mL at initial diagnosis had poor OS compared with patients in group of <25.96 pg/mL at initial diagnosis. Conclusions: Use of liquid biopsy of circulating exosomal PD-L1 at initial diagnosis provides a robust means of predicting prognosis for patients with a newly diagnosed osteosarcoma.

Purpose: This retrospective cohort study aimed to investigate the association between intraoperative dexmedetomidine infusion and emergence agitation (EA), and recovery profiles after lung surgery in adult patients. It was hypothesized that dexmedetomidine was associated with reduced EA and improved recovery profiles. Patients and methods: A single-center chart review was conducted on elective lung surgeries in adults between January and December 2016. The primary outcome was the incidence of EA in postanesthesia care units (PACUs). The secondary outcomes included rescue analgesia, shivering, time to extubation, residual sedation, postoperative pulmonary events, duration of PACU stay, length of hospital stay, and intraoperative hemodynamic changes. Univariate and multivariate regression analyses were used to analyze data. Results: Among 2,468 patients, 814 received an intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower incidence of EA (10.9% vs 15.0%; adjusted OR, 0.67; 95% CI, 0.51–0.87; P=0.003), rescue analgesia (7.6% vs 12.2%; adjusted OR, 0.63; 95% CI, 0.47–0.86; P=0.003), shivering (4.2% vs 6.6%; adjusted OR, 0.58; 95% CI, 0.38–0.88; P=0.010), and intraoperative bradycardia (18.6% vs 12.6%; adjusted OR, 1.51; 95% CI, 1.19–1.92; P=0.001). No differences were observed in residual sedation, duration of PACU stay, postoperative pulmonary events, and length of hospital stay between the groups. Conclusion: This retrospective study suggested that intraoperative dexmedetomidine infusion was associated with a lower incidence of EA, rescue analgesia, and shivering in adults after lung surgery. Intraoperative bradycardia was the main side effect.

Objective: This systematic review and meta-analysis aimed to determine the effect of preoperative denosumab on the local recurrence of giant-cell tumor of bone (GCTB) treated with curettage.