Semaphorins are a large class of secreted or membrane-associated proteins that act as chemotactic cues for cell movement via their transmembrane receptors, plexins. We hypothesized that the function of the semaphorin signaling pathway in the control of cell migration could be harnessed by cancer cells during invasion and metastasis. We now report 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene. Mutations were found in 89% (8 of 9) of prostate cancer bone metastases, in 41% (7 of 17) of lymph node metastases, and in 46% (41 of 89) of primary cancers. Forty percent of prostate cancers contained the same mutation. Overexpression of the Plexin-B1 protein was found in the majority of primary tumors. The mutations hinder Rac and R-Ras binding and R-RasGAP activity, resulting in an increase in cell motility, invasion, adhesion, and lamellipodia extension. These results identify a key role for Plexin-B1 and the semaphorin signaling pathway it mediates in prostate cancer.adhesion ͉ migration ͉ R-Ras ͉ Rac ͉ semaphorin

No abstract

No abstract

No abstract

No abstract

Calcific uremic arteriolopathy or calciphylaxis is a rare condition that can present with clinical features similar to penile cancer. It is a diagnosis to consider in patients with end-stage renal failure (ESRF) presenting with a penile lesion. We describe one such case, where a patient with ESRF presented with a solid, tender penile mass and underwent surgery for presumed penile cancer. Histopathological analysis however confirmed a diagnosis of calcific uremic arteriolopathy, without evidence of malignancy. The clinical diagnosis of calcific uremic arteriolopathy relies on a high index of suspicion, and lesion biopsy is controversial due to a high risk of poor wound healing and sepsis. New treatment options are encouraging, and have been reported, albeit in small numbers. Delayed diagnosis can adversely affect both quality of life and prognosis in a condition with an extremely high mortality rate.

No abstract

Aims Post‐prostatectomy stress urinary incontinence (PPI) is a common condition with significant impact on patient quality of life. With rising numbers of prostatectomies performed, recognition of incontinence during survivorship care is growing. With increasing hesitance of the use of suburethral mesh in females, urethral bulking injections in this patient population as a minimally invasive alternative to surgery are evaluated. This review aims to evaluate the existing evidence base for urethral bulking therapy in PPI and provide a summary of its efficacy, durability, and side‐effect profile. Methods A literature search of Medline/Pubmed and Cochrane databases was conducted to identify publications reporting the clinical outcomes of urethral bulking injections in patients with PPI, up to and including October 1st, 2018. Case reports, letters and reviews were excluded. Results We identified 25 studies that fit our inclusion criteria, comprised of one RCT, two large retrospective cohort studies, and 22 case series. The success rates reported varying widely from 13%‐100% with reports of symptomatic control deterioration. Complication rates remain low. This review highlighted a poor performance using the more historic bulking agents (BA), and the lack of strong evidence with the more novel BA in PPI and discussed challenges regarding optimal patient selection and techniques. Conclusions There exists poor clinical evidence base concerning the use of urethral bulking in PPI with few high‐level studies and a significant lack of consistency between studies. Further study in this area is required to evaluate the role of BA in this patient population.