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.

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.

Background: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. Methods: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. Results: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). Conclusions: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

Background: While various implants are currently used for the treatment of femoral trochanteric fractures in Japan, 'mismatches' have been known to occur between patient and implant type. The purpose of this study is to identify morphological characteristics of elderly Japanese females, both in terms of the shape of proximal femur and its anterior curvature in order to evaluate the suitability of implants for treatment of femoral trochanteric fractures using 3D-computed tomography (CT) scanning. Methods: This study used CT scan data taken from 50 elderly females (aged 70 years or older). Neck-shaft (NS) angle and height of the greater trochanter (GT) were measured under defined conditions (TPI: theoretical plane to place implant). Anterior curvature of the femoral shaft was also measured. Results: On average, the NS angle was found to be 128.1 and GT height was 62.4 mm. Average curvature radius was 1040 mm. As for the NS angle, the centrum-collum-diaphysis angles of existing implants (125 or 130) are reasonable. In elderly Japanese patients, the proximal femur shows specific characteristics. As GT height is very short, the implant may easily interfere with the lateral cortex. Additionally, the curvature radius calculated (1040 mm) was smaller than that of past reports, indicating strong curvature in the Japanese elderly. Conclusion: Our measurement results are potentially useful in the avoidance of intraoperative trouble caused by mismatch of implants.

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