Clinical Features, Treatment, and Outcome in 102 Adult and Pediatric Patients with Localized High-Grade Synovial Sarcoma

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive

Oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch

Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show that 3D mesenchymal cell intercalations are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor that we knock-in to the mouse genome, we show that cortical force oscillations promote these intercalations. Genetic loss- and gain-of-function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity and cytoskeletal oscillation. These processes diminish tissue rigidity and help cells to overcome the energy barrier to intercalation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin polarity and cytosolic calcium transients that orient and drive mesenchymal cell intercalations. These findings advance our understanding of how developmental pathways regulate biophysical properties and forces to shape a solid organ primordium

Can Neonatal Pelvic Osteotomies Permanently Change Pelvic Shape in Patients with Exstrophy?: Understanding Late Rediastasis

Pelvic osteotomies are frequently used as part of the surgical management of bladder exstrophy. The outcomes are often measured on the basis of the residual symphyseal diastasis. The aims of this study were to evaluate and validate a more reliable radiographic measure of ischiopubic rotation, to utilize this measure in analyzing pelves from patients with exstrophy and controls, and to propose a model for rediastasis in a pelvis with exstrophy.Pelvic radiographs of 164 normal children two months to eighteen years of age were used to determine the changes in interpubic and interischial distances and in the interischial/interpubic (IS/IP) ratio with age. Twenty-one pelvic CT (computed tomography) studies of normal children, two to sixteen years of age, were also used to study the change in the ischiopubic divergence angle. The same parameters were measured on radiographs or CT or magnetic resonance imaging studies of seventy-three patients with classic bladder exstrophy who were followed for two to nineteen years after exstrophy closure with or without pelvic osteotomies.In normal children, the interpubic distance and the ischiopubic divergence angle had a narrow range and were constant with age, whereas the interischial distance and the IS/IP ratio increased progressively and were strongly correlated with age. In the patients with exstrophy, the interpubic distance was positively correlated with the interischial distance, whereas the IS/IP ratio was lower than that in normal controls and was not correlated with age.The IS/IP ratio is a useful measure of ischiopubic rotation and can be used to characterize pelvic growth, including the phenomenon of rediastasis in patients with exstrophy. Pelvic rediastasis is a progressive increase in interpubic distance resulting from growth without loss of rotational correction, as shown by the constancy of the IS/IP ratio with age in these patients. A better rotational position at the time of osteotomy may lead to a better pelvic shape at maturity.Symphyseal rediastasis following neonatal pelvic osteotomies in patients with exstrophy is not due to loss of correction and progressive derotation of the hemipelves but is a consequence of the normal three-dimensional growth of the pelvis. The best correction of the pelvic deformity should always be the aim even in neonatal pelvic osteotomies because this will permanently change the pelvic shape

Can Neonatal Pelvic Osteotomies Permanently Change Pelvic Shape in Patients with Exstrophy?: Understanding Late Rediastasis

Pelvic osteotomies are frequently used as part of the surgical management of bladder exstrophy. The outcomes are often measured on the basis of the residual symphyseal diastasis. The aims of this study were to evaluate and validate a more reliable radiographic measure of ischiopubic rotation, to utilize this measure in analyzing pelves from patients with exstrophy and controls, and to propose a model for rediastasis in a pelvis with exstrophy.Pelvic radiographs of 164 normal children two months to eighteen years of age were used to determine the changes in interpubic and interischial distances and in the interischial/interpubic (IS/IP) ratio with age. Twenty-one pelvic CT (computed tomography) studies of normal children, two to sixteen years of age, were also used to study the change in the ischiopubic divergence angle. The same parameters were measured on radiographs or CT or magnetic resonance imaging studies of seventy-three patients with classic bladder exstrophy who were followed for two to nineteen years after exstrophy closure with or without pelvic osteotomies.In normal children, the interpubic distance and the ischiopubic divergence angle had a narrow range and were constant with age, whereas the interischial distance and the IS/IP ratio increased progressively and were strongly correlated with age. In the patients with exstrophy, the interpubic distance was positively correlated with the interischial distance, whereas the IS/IP ratio was lower than that in normal controls and was not correlated with age.The IS/IP ratio is a useful measure of ischiopubic rotation and can be used to characterize pelvic growth, including the phenomenon of rediastasis in patients with exstrophy. Pelvic rediastasis is a progressive increase in interpubic distance resulting from growth without loss of rotational correction, as shown by the constancy of the IS/IP ratio with age in these patients. A better rotational position at the time of osteotomy may lead to a better pelvic shape at maturity.Symphyseal rediastasis following neonatal pelvic osteotomies in patients with exstrophy is not due to loss of correction and progressive derotation of the hemipelves but is a consequence of the normal three-dimensional growth of the pelvis. The best correction of the pelvic deformity should always be the aim even in neonatal pelvic osteotomies because this will permanently change the pelvic shape