The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2. Animal experiments revealed a close correlation between serum miR-92b-3p levels and tumour dynamics. Clinical relevance was validated in two independent clinical cohorts, and we subsequently identified that serum miR-92b-3p levels were significantly higher in SS patients in comparison to that in healthy individuals. Moreover, serum miR-92b-3p was robust in discriminating patients with SS from the other STS patients and reflected tumour burden in SS patients. Overall, liquid biopsy using serum miR-92b-3p expression levels may represent a novel approach for monitoring tumour dynamics of SS.

BackgroundPlate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method.MethodsThis retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them.ResultsOf 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm.Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes.ConclusionsWe concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

Background: Recently, arthroscopic ankle arthrodesis has been performed for moderate-to-severe varus-deformed ankle osteoarthritis. However, the effect of osteophyte resection in the lateral gutter in arthroscopic ankle arthrodesis has not been clarified. We hypothesized that a varus-deviated ankle with lateral gutter osteophytes can be corrected by osteophyte resection. Methods: Thirty-nine ankles of 38 patients were included. The mean age of patients was 70.0 (45-83) years. The patients were divided into the following groups: group with an osteophyte in the lateral gutter (osteophyte) and group with no osteophytes (nonosteophyte). Preoperative and postoperative tibiotalar angle, tibial plafond angle, and tibiotalar angle under valgus stress, as well as the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, were recorded. Twelve ankles underwent lateral gutter osteophyte resection, whereas the other 27 ankles did not require osteophyte resection. Results: Preoperative tibiotalar angle was higher in the osteophyte group than in the nonosteophyte group (21.8 vs 11.2 degrees, P = .01). The tibiotalar angle in the preoperative valgus stress imaging was higher in the osteophyte group (12.9 vs 5.7, P < .01). However, the postoperative tibiotalar angle was similar between the 2 groups (7.1 vs 5.4, P = .183). JSSF ankle/hindfoot scale improved in both groups. Conclusion: Lateral gutter osteophyte resection enabled correction of the varus malalignment in arthroscopic ankle arthrodesis. Level of Evidence: Level III, retrospective comparative series.

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment. Lack of blood-based biomarkers is a major problem in the management of bone and soft tissue sarcomas (STSs). Detection of primary and/or recurrent tumors has generally relied on local symptoms and imaging modalities. Myxofibrosarcoma (MFS), one of the most common locally aggressive STSs 1,2 , is no exception. MFS comprises a spectrum of malignant fibroblastic lesions with variably myxoid stroma, pleomorphism, and a distinct curvilinear vascular pattern 3. In addition, it is clinically characterized by infiltrative growth into surrounding soft tissues 4-6. The infiltrative growth pattern is observed as a tail-like pattern on MRI and high correlations (87-100%) between radiological and pathological infiltration have been reported 7-9. Since the efficacy of radiotherapy and chemotherapy are limited in MFS, surgical resection with a wide margin is standard treatment 4-6. However, the local recurrence rate is high, ranging from 22% to 79%, even after wide resection 1,8,10,11 , and infiltrative growth is recognized as a primary risk factor for local recurrence and possibly distant metastasis 4-6,12-14. Approximately 30% of recurrent MFS progress to higher grade tumors, which exhibit increased metastatic potential and poor prognosis 15. However, there is no biomarker for monitoring tumor recurrence and the molecular mechanisms underlying the infiltrative nature of MFS remain unknown. Emerging evidence suggests that microRNAs (miRNAs) play a crucial role in tumor initiation, progression, and metastasis 16-18. miRNAs are small, non-coding RNA molecules consisting of approximat...

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.