Oxidative stress and inflammation may be key factors in the development of bladder overactivity in atherosclerosis-induced chronic bladder ischemia.

Abbreviations & AcronymsAbstract: Robot-assisted radical prostatectomy has been shown to have comparable and possibly improved postoperative continent rates compared with retropubic and laparoscopic radical prostatectomy. However, postoperative urinary incontinence has remained one of the most bothersome postoperative complications. The basic concept of the intraoperative technique to improve postoperative urinary continence is to maintain as normal anatomical and functional structure in the pelvis as possible. Therefore, improved knowledge of the normal structure in the pelvis should lead to a greater understanding of the pathophysiology of urinary incontinence, and further development of intraoperative techniques to improve the outcomes of urinary continence. It might be necessary to carry out three steps to realize improvement of the early return of urinary continence after robot-assisted radical prostatectomy: (i) preservation (bladder neck, neurovascular bundle, puboprostatic ligament, pubovesical complex, and/or urethral length, etc.); (ii) reconstruction (posterior and/or anterior reconstruction, and/or reattachment of the arcus tendineus to the bladder neck, etc.); and (iii) reinforcement (bladder neck plication and/or sling suspension, etc.). On the basis of these steps, further modifications during robot-assisted radical prostatectomy should be developed to improve urinary continence and quality of life after robot-assisted radical prostatectomy.

Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens. Cell proliferation and signal transduction activity were then quantified after co-treatment with tocilizumab, an IL-6R inhibitor, in vitro and in vivo. 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. Using a mouse xenograft model we can show that a combination therapy with tocilizumab and low dosage of sorafenib suppresses 786-O tumor growth, reduces AKT-mTOR pathway and inhibits angiogenesis in vivo more efficient than sorafenib alone. Furthermore FDG-PET imaging detected early decrease of maximum standardized uptake values prior to extended central necrosis.Our findings suggest that a combination therapy of IL-6R inhibitors and TKIs may represent a novel therapeutic approach for RCC treatment.

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