An anatomic study of coronoid cartilage thickness with special reference to fractures.

BACKGROUND: Current coronoid fracture classification systems are based on fragment size and configuration using plain radiographs and/or computed tomography (CT). During surgery, coronoid fracture fragments appear much larger than anticipated because cartilage is radiolucent and therefore not accounted for with preoperative imaging. The purpose of this imaging study was to quantify the articular cartilage thickness of the coronoid, with reference to coronoid fractures. MATERIALS AND METHODS: Twenty-four cadaveric ulnae were dissected, imaged with CT, and analyzed by use of image analysis software. Thirteen identifiable landmarks were chosen on the coronoid, olecranon, and proximal radioulnar joint to measure articular cartilage thickness. Intraobserver reliability and interobserver reliability were determined. RESULTS: Cartilage thickness was highest at the coronoid tip, with a mean of 3.0 mm (range, 1.7-4.6 mm). Cartilage thickness at the tip correlated inversely with age (P < .01) and correlated strongly with overall ulnar height and ulnar length (P < .05). All measurements had excellent intraobserver and interobserver reliability. CONCLUSION: The thickness of cartilage on the coronoid tip is not inconsequential. The results of this study indicate that a 2-mm coronoid tip fracture on CT scan may actually appear to be a mean of 5 mm thick when viewed at the time of surgery. Clinically, this is important because it may alter the classification, the decision to treat, or the type of fixation used. Importantly, biomechanical cadaveric studies assessing coronoid injuries have incorporated cartilage thickness into coronoid size measurements when creating simulated fractures; therefore, it is critical that the conclusions of such biomechanical studies be scrutinized with regard to their clinical recommendations. Surgeons should be aware of these discrepancies.

TGFß signaling regulates epithelial-mesenchymal plasticity in ovarian cancer ascites-derived spheroids.

Epithelial-mesenchymal transition (EMT) serves as a key mechanism driving tumor cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFß) signaling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFß signaling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a substratum. CDH1/E-cadherin expression was markedly reduced in spheroids compared with adherent cells, in concert with an up-regulation of several transcriptional repressors, i.e., SNAI1/Snail, TWIST1/2, and ZEB2. Treatment of EOC spheroids with the TGFß type I receptor inhibitor, SB-431542, potently blocked the endogenous activation of EMT in spheroids. Furthermore, treatment of spheroids with SB-431542 upon re-attachment enhanced the epithelial phenotype of dispersing cells and significantly decreased cell motility and Transwell migration. Spheroid formation was significantly compromised by exposure to SB-431542 that correlated with a reduction in cell viability particularly in combination with carboplatin treatment. Thus, our findings are the first to demonstrate that intact TGFß signaling is required to control EMT in EOC ascites-derived cell spheroids, and it promotes the malignant characteristics of these structures. As such, we show the therapeutic potential for targeted inhibition of this pathway in ovarian cancer patients with late-stage disease.