Extra-articular hip resection with maintenance of pelvic continuity in malignant tumours of the proximal femur with articular invasion.

INTRODUCTION: Extra-articular hip resection may be necessary in cases of malignant tumour of the pelvic bone or of the proximal femur invading the hip joint. When the tumour is in the proximal femur, it is possible to resect the acetabulum en bloc by performing a periacetabular osteotomy, but this creates a discontinuity in the pelvic ring with difficult reconstruction and diminished function. Several techniques described recently seek to be as sparing as possible on the pelvic bone by preserving the posterior column or both columns in order to facilitate reconstruction and improve function. However, these still require complex reconstructions and can necessitate intra-pelvic dissection. TECHNIQUE: We describe here an extra-articular hip resection technique for tumours of the proximal femur invading the joint, with maintenance of pelvic continuity by preserving both columns and the quadrilateral plate of the acetabulum, without intra-pelvic dissection, that can be performed on patients in whom the medial wall of the acetabulum is thick enough. Our preliminary assessments have included studies on dry bone and imaging analyses. The technique was first tested on a single cadaver pelvis (encompassing 2 hips) and subsequently performed on a patient with a pathological fracture of the femoral neck due to osteosarcoma secondary to Paget's disease. CONCLUSIONS: Further clinical applications are essential to evaluate the overall effectiveness, safety and impact on patient functionality of this experimental technique.

Preoperative Planning for Reverse Shoulder Arthroplasty: Does the Clinical Range of Motion Match the Planned 3D Humeral Displacement?

INTRODUCTION: The functional outcome after reverse shoulder arthroplasty (RSA) is closely linked to how much the humerus shifts because of the implants. While two-dimensional (2D) angle measurements have been used to capture this shift, it can be measured in three dimensions (3D) as the arm change position (ACP). In a previous study, the ACP was measured using 3D preoperative planning software with the passive virtual shoulder range of motion obtained after RSA. The main objective of this study was to evaluate the relationship between the ACP and the actual active shoulder range of motion measured after RSA. The hypothesis was that the ACP and the active clinical range of motion are related such that the ACP is a reliable parameter to guide the preoperative planning of an RSA. The secondary objective was to assess the relationship between 2D and 3D humeral displacement measurements. MATERIALS AND METHODS: This prospective observational study enrolled 12 patients who underwent RSA and had a minimum follow-up of 2 years. The active range of motion in shoulder flexion, abduction, and internal and external rotation was measured. At the same time, ACP measurements were taken from a reconstructed postoperative CT scan, in addition to the radiographic measurements of humeral lateralization and distalization angles on AP views in neutral rotation. RESULTS: The mean humeral distalization induced by RSA was 33.3 mm (±3.8 mm). A non-statistically significant increase in shoulder flexion was observed for humeral distalization beyond 38 mm (R2 = 0.29, p = 0.07). This "threshold" effect of humeral distalization was also observed for the gains in abduction, as well as internal and external rotations, which seemed better with less than 38 mm or even 35 mm distalization. No statistical correlation was found between the 3D ACP measurements and 2D angle measurements. CONCLUSION: Excessive humeral distalization seems to be detrimental to joint mobility, especially shoulder flexion. Humeral lateralization and humeral anteriorization measured using the ACP seem to promote better shoulder range of motion, with no threshold effect. These findings could be evidence of tension in the soft tissues around the shoulder joint, which should be taken into consideration during preoperative planning.

A calpain-6/YAP axis in sarcoma stem cells that drives the outgrowth of tumors and metastases.

Sarcomas include cancer stem cells, but how these cells contribute to local and metastatic relapse is largely unknown. We previously showed the pro-tumor functions of calpain-6 in sarcoma stem cells. Here, we use an osteosarcoma cell model, osteosarcoma tissues and transcriptomic data from human tumors to study gene patterns associated with calpain-6 expression or suppression. Calpain-6 modulates the expression of Hippo pathway genes and stabilizes the hippo effector YAP. It also modulates the vesicular trafficking of ß-catenin degradation complexes. Calpain-6 expression is associated with genes of the G2M phase of the cell cycle, supports G2M-related YAP activities and up-regulated genes controlling mitosis in sarcoma stem cells and tissues. In mouse models of bone sarcoma, most tumor cells expressed calpain-6 during the early steps of tumor out-growth. YAP inhibition prevented the neoformation of primary tumors and metastases but had no effect on already developed tumors. It could even accelerate lung metastasis associated with large bone tumors by affecting tumor-associated inflammation in the host tissues. Our results highlight a specific mechanism involving YAP transcriptional activity in cancer stem cells that is crucial during the early steps of tumor and metastasis outgrowth and that could be targeted to prevent sarcoma relapse.

Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers.

Metastases of osteosarcomas are heterogeneous. They may grow simultaneously with the primary tumor, during treatment or shortly after, or a long time after the end of the treatment. They occur mainly in lungs but also in bone and various soft tissues. They can have the same histology as the primary tumor or show a shift towards a different differentiation path. However, the metastatic capacities of osteosarcoma cells can be predicted by gene and microRNA signatures. Despite the identification of numerous metastasis-promoting/predicting factors, there is no efficient therapeutic strategy to reduce the number of patients developing a metastatic disease or to cure these metastatic patients, except surgery. Indeed, these patients are generally resistant to the classical chemo- and to immuno-therapy. Hence, the knowledge of specific mechanisms should be extended to reveal novel therapeutic approaches. Recent studies that used DNA and RNA sequencing technologies highlighted complex relations between primary and secondary tumors. The reported results also supported a hierarchical organization of the tumor cell clones, suggesting that cancer stem cells are involved. Because of their chemoresistance, their plasticity, and their ability to modulate the immune environment, the osteosarcoma stem cells could be important players in the metastatic process.