Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer.

The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan-Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

Stone-Free Rate after Treating Kidney Stones Exceeding 10 mm via Flexible Ureteroscopy: Can Endoscopic Assessment Replace Low-Dose Computed Tomography Control?

INTRODUCTION: It is unclear whether endoscopic assessment of the stone-free rate after flexible ureteroscopy (fURS) is as effective as assessment with low-dose computed tomography (CT) scan. METHODS: Prospective documentation of patients with kidney stones > 10 mm diameter from 2 different centers (Freiburg, Regensburg), who underwent fURS and were declared to be endoscopically completely stone-free. Low-dose CT control performed 4-8 weeks postoperatively. RESULTS/CONCLUSION: Thirty-eight patients were treated between October 2015 and August 2016 (12 F, 26 M). Average age was 55.9 years (range 19-82, SD 17.24), and body mass index was 29.7 kg/m2 (range 23.5-42.5, SD 4.37). There were 2.0 (range 1-7, SD 1.55) stones with a mean diameter of 15 mm (range 10-40, SD 6.78) per kidney. Mean surgery time was 74 min (range 38-124, SD 24.28), and lithotripsy was necessary in 33 cases. CT was performed 5.4 weeks afterwards (range 4-8, SD 1.43). One patient had a 2 mm residual which was extracted by URS. Strictly speaking, endoluminal stone removal control failed in only that patient, yielding a negative predictive value of 97%. A routine postoperative CT scan would thus appear unnecessary in the case of negative endoscopic control for residual fragments and should be avoided to reduce radiation exposure. Further investigations with larger patient populations are necessary.

Incidence, Risk Factors and Management of Symptomatic Lymphoceles after Radical Retropubic Prostatectomy.

INTRODUCTION: We investigated the incidence, clinical course and risk factors for symptomatic lymphoceles after radical retropubic prostatectomy with pelvic lymph node dissection. Moreover, we explored parameters for the failure of percutaneous lymphocele drainage. METHODS: The incidence of symptomatic lymphoceles in patients with prostate cancer who underwent radical retropubic prostatectomy with pelvic lymph node dissection in our department between 2008 and 2013 was investigated retrospectively. The occurrence of lymphoceles was correlated with several clinical and histopathological parameters. In addition, logistic regression analysis was performed to assess the value of independent variables with regard to the development of symptomatic lymphoceles and failure of percutaneous drainage. RESULTS: A total of 599 consecutive patients treated with radical retropubic prostatectomy with pelvic lymph node dissection were included in the study, of whom symptomatic lymphocele had developed in 5%. Median time to diagnosis of symptomatic lymphocele was 22.5 days. Median time of percutaneous drainage was 16 days. Overall 43% of patients required surgical unroofing. On multivariate analysis age greater than 67 years (OR 3.27, p=0.005) and removal of more than 10 lymph nodes (OR 2.57, p=0.018) were independent predictors for the development of symptomatic lymphoceles. A significantly increased risk of percutaneous drainage failure was observed in patients who had a body mass index greater than 27 kg/m2 (OR 7.0, p=0.03), followed by a trend for those with a drainage volume of more than 375 ml 24 hours after puncture (OR 3.89, p=0.12). CONCLUSIONS: Symptomatic lymphocele will develop in 1 of 20 patients after radical retropubic prostatectomy with pelvic lymph node dissection. The number of lymph nodes removed constitutes an independent risk factor. Percutaneous drainage failure is associated with high body mass index and high drainage volume within the first 24 hours after puncture.

Online Discussion on #KidneyStones: A Longitudinal Assessment of Activity, Users and Content.

INTRODUCTION: Twitter is a popular microblogging platform for the rapid dissemination of information and reciprocal exchange in the urological field. We aimed to assess the activity, users and content of the online discussion, #KidneyStones, on Twitter. METHODS: We investigated the Symplur Signals analytics tool for Twitter data distributed via the #KidneyStones hashtag over a one year period. Activity analysis reflected overall activity and tweet enhancements. We assessed users' geolocations and performed an influencer analysis. Content analysis included the most frequently used words, tweet sentiment and shares for top tweets. RESULTS: 3,426 users generated over 10,333 tweets, which were frequently accompanied by links (49%), mentions (30%) and photos (13%). Users came from 106 countries across the globe and were most frequently from North America (63%) and Europe (16%). Individual and organisational healthcare professionals made up 56% of the influencers of the Twitter discussion on #KidneyStones. Besides the words 'kidney' (used 4,045 times) and 'stones' (3,335), 'pain' (1,233), 'urine' (1,158), and 'risk' (1,023) were the most frequently used words. 56% of tweets had a positive sentiment. The median (range) number of shares was 85 (62-587) for the top 10 links, 45.5 (17-94) for the top 10 photos, and 44 (22-95) for the top 10 retweets. CONCLUSION: The rapidly growing Twitter discussion on #KidneyStones engaged multiple stakeholders in the healthcare sector on a global scale and reached both professionals and laypeople. When used effectively and responsibly, the Twitter platform could improve prevention and medical care of kidney stone patients.

Assessment of a modified acoustic lens for electromagnetic shock wave lithotripters in a swine model.

PURPOSE: The acoustic lens of the Modularis electromagnetic shock wave lithotripter (Siemens, Malvern, Pennsylvania) was modified to produce a pressure waveform and focal zone more closely resembling that of the original HM3 device (Dornier Medtech, Wessling, Germany). We assessed the newly designed acoustic lens in vivo in an animal model. MATERIALS AND METHODS: Stone fragmentation and tissue injury produced by the original and modified lenses of the Modularis lithotripter were evaluated in a swine model under equivalent acoustic pulse energy (about 45 mJ) at 1 Hz pulse repetition frequency. Stone fragmentation was determined by the weight percent of stone fragments less than 2 mm. To assess tissue injury, shock wave treated kidneys were perfused, dehydrated, cast in paraffin wax and sectioned. Digital images were captured every 120 µm and processed to determine functional renal volume damage. RESULTS: After 500 shocks, the mean ± SD stone fragmentation efficiency produced by the original and modified lenses was 48% ± 12% and 52% ± 17%, respectively (p = 0.60). However, after 2,000 shocks, the modified lens showed significantly improved stone fragmentation compared to the original lens (mean 86% ± 10% vs 72% ± 12%, p = 0.02). Tissue injury caused by the original and modified lenses was minimal at a mean of 0.57% ± 0.44% and 0.25% ± 0.25%, respectively (p = 0.27). CONCLUSIONS: With lens modification the Modularis lithotripter demonstrates significantly improved stone fragmentation with minimal tissue injury at a clinically relevant acoustic pulse energy. This new lens design could potentially be retrofitted to existing lithotripters, improving the effectiveness of electromagnetic lithotripters.

EAU guidelines on assessment and nonsurgical management of urinary incontinence.

CONTEXT: The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence. A decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel, using a sustainable methodology. OBJECTIVE: We present a short version of the full guidelines on assessment, diagnosis, and nonsurgical treatment of urinary incontinence, with the aim of increasing their dissemination. EVIDENCE ACQUISITION: Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches, based on Population, Intervention, Comparator, Outcome questions. Appraisal of papers was carried out by an international panel of experts, who also collaborated on a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY: The full version of the guidelines is available online (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include algorithms that refer the reader back to the supporting evidence, and they are more immediately useable in daily clinical practice. CONCLUSIONS: These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where such evidence does not exist, they present a consensus of expert opinion.