Nonvascularized fibular graft with locking screw fixation for metaphyseal bone loss of distal femur: biomechanical assessment validated by a clinical case series.

BACKGROUND: The optimal modality to surgically treat significant bone loss of distal femur remains inconclusive. The objectives of the present study were to assess the mechanical performance of nonvascularized fibular graft (NVFG) with locking screw fixation in distal femur fixation construct by finite element analysis and to retrospectively describe the outcomes of the present technique in clinical cases. METHODS: Four constructs which the fractured femur was stabilized by LCP-DF alone, dual plating, LCP-DF combined with NVFG, and LCP-DF combined with NVFG (LCP-DF-NVFG-S) with locking screw were assessed the biomechanical performance under physiological loads. For the clinical case series, 12 patients with open intercondylar fracture with metaphyseal bone loss of distal femur were operated by LCP-DF-NVFG-S. The collected data included fracture consolidation, length of NVFG, perioperative complications and objective clinical results. RESULTS: LCP-DF-NVFG-S demonstrated lower implant equivalent von Mises stress (EQV) stress and better fracture stability than other constructs. A locking screw presented its essence in maintaining the NVFG in the required position and subsequently enhancing the fracture stability. In regard to the clinical series, all fractures were consolidated with an average duration of 27.8 weeks (range 20-32). An average NVFG length was 7.8 cm (range 6-12). No perioperative complication was demonstrated. By the Knee Society score, 1 was considered to be excellent, 9 to be good and 2 to be poor. CONCLUSION: Based on the results of mechanical assessment and case series, LCP-DF-NVFG-S can be an effective technique in the management of metaphyseal bone loss of distal femur.

Calpain system protein expression and activity in ovarian cancer.

PURPOSE: Expression of members of the calpain system are associated with clinical outcome of patients with, amongst others, breast and ovarian cancers, with calpain-2 expression in ovarian cancer being implicated in chemo-resistance and survival. This study aimed, using a large patient cohort and in vitro models, to verify its importance and further investigate the role in ovarian cancer chemoresponse. METHODS: Calpain-1, calpain-2, calpain-4 and calpastatin expression were evaluated in primary ovarian carcinomas (n = 575) by immunohistochemistry. Protein expression was assessed, via western blotting, in five ovarian cancer cell lines with various sensitivities towards cisplatin/carboplatin. In vitro calpain activity was inhibited by calpeptin treatment to assess changes in platinum sensitivity by proliferation assay, with expression of genes associated with epithelial-mesenchymal transition being examined by RT2 Profiler™ PCR Array. RESULTS: The current study confirmed previous data that high calpain-2 expression is associated with poor overall survival (P = 0.026) and that calpain-1 was not associated with overall survival or progression-free survival. Low expression of calpastatin (P = 0.010) and calpain-4 (P = 0.003) were also associated with adverse survival. Such prognostic associations do not seem to be linked with altered tumour sensitivity towards platinum-based chemotherapy. Interestingly, low calpain-1 expression was more frequent in patients with confined tumours (stage 1) (χ2 = 11.310, df = 1, P = 0.001). Calpain and calpastatin expression varied among ovarian cancer cell lines yet their expression levels were similar between chemo-sensitive cells and resistant counterparts. Moreover, calpeptin treatment did not alter cellular response to platinum-based chemotherapy or epithelial-mesenchymal transition-related gene expression. CONCLUSIONS: The conventional calpains and calpastatin have been confirmed to play an important role in ovarian cancer; however, the precise mechanisms whereby they exert effects remain to be elucidated.