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Zusammenfassung. Dieser Übersichtsartikel beleuchtet den aktuellen Kenntnisstand zur Ätiologie, Diagnostik und Therapie der Harninkontinenz des Mannes. In der Ätiologie der Harninkontinenz beim Mann spielt die radikale Prostatektomie eine herausragende Rolle, aber auch das benigne Prostatasyndrom, neurologische Erkrankungen oder metabolische Störungen können zu einer Harninkontinenz beim Mann führen. In der Diagnostik ist neben der Basisdiagnostik eine qualifizierte urodynamische Beurteilung unabdingbar, um die zugrunde liegenden pathophysiologischen Mechanismen aufzudecken und Chancen und Risiken der verfügbaren Therapie- bzw. Operationstechniken abschätzen zu können. Die Primärtherapie der Harninkontinenz beim Mann ist konservativ und schliesst eine qualifizierte Beckenboden- und Sphinktertherapie einschliesslich Biofeedback ein. Die Auswahl der operativen Techniken unterliegt dem Ausmass der Inkontinenz, den individuellen Gegebenheiten des Patienten, der Patientenpräferenz, der Expertise des Operateurs und einzelnen Kontraindikationen für bestimmte Verfahren. Auch ein längeres Intervall nach radikaler Prostatektomie oder ein Tumorprogress sind keine Ausschlusskriterien für eine operative Therapie. Der oft hohe Leidensdruck und das breite Spektrum von in geübten Händen wenig invasiven Operationstechniken rechtfertigen eine breite Indikationsstellung für eine prothetische Versorgung.

Osteonekrosen des Kiefers unter laufender knochenprotektiver Behandlung mit Zoledronsaure oder Denosumab sind eine schwerwiegende Komplikation bei Patienten mit einem ossar metastasiertem kastrationsrefraktarem Prostatakarzinom. Je fruher eine medikamentenasso-ziierte Osteonekrose des Kiefers erkannt wird, desto groser ist der Erfolg einer konservativen Therapie. Erste Daten zeigen, dass das Knochenszintigramm fruhzeitig Hinweise auf eine bevorstehende oder vorliegende Osteonekrose des Kiefers geben kann.

Objective To investigate the impact of the antibiotic coating InhibiZone on the infection and explantation rates of the AMS 800 in comparison to the AMS 800 without InhibiZone. Materials and Methods We retrospectively identified 305 patients with an AMS 800 in a multicenter cohort study. Patients were subsequently divided into InhibiZone and without InhibiZone-coated groups. Infection and explantation rates were analyzed by univariate and consecutively by multivariate logistic regression adjusted to variable risk factors. The infection-free interval was estimated by Kaplan-Meier plot and compared by the log-rank test. A P value below .05 was considered statistically significant. Results We identified 47 patients with InhibiZone and 258 without InhibiZone coating. In univariate analysis, we could not identify a significant difference in infection (P = .932) or explantation (P = .715) rates between the groups. In multivariate analysis, impaired wound healing (P = .008) and urethral erosion (P

Zusammenfassung Fragestellung Die vorliegende Studie vergleicht die unipolare und die bipolare Stimulationstechnik während des Peripheren Nervenevaluationstestes der Sakralen Neuromodulation in einer Kohorte von 100 Patienten mit nicht-neurogenen und neurogenen Harntraktfunktionsstörungen und überprüft die Hypothese, dass die bipolare Technik der unipolaren bezogen auf die Testeffektivität überlegen ist. Material und Methoden In diese Fall-Kontroll-Studie wurden 43 Patienten mit biopolarer und 57 Patienten mit unipolarer Stimulation eingeschlossen. Für die bipolare Stimulation wurden vier Elektroden an S3 und S4 beidseits platziert und die Elektroden von S3 und S4 jeder Seite elektrisch verbunden. In einem Testprotokoll über acht Tage wurde die Wirksamkeit der Stimulation überprüft. Nach Ende der Testphase wurden die Elektroden entfernt und das Ergebnis mit Hilfe der Miktionstagebücher ermittelt. Als Vergleichsgruppe diente eine Kohorte mit 57 Patienten und unipolarer Stimulation (aktive Elektrode an der Sakralwurzel und passive Elektrode auf der Haut). Results Das unipolare Testverfahren war erfolgreich in 47 % (27 /57), das bipolare in 58 % (25 /43). In der bipolaren Gruppe profitierten 63 % (12/19) mit neurogener Harntraktfunktionsstörung vs. 57 % (13/23) in der unipolaren Gruppe. Ohne neurologisches Leiden wiesen bei bipolarer 58 % (14/24) einen erfolgreichen Test auf vs. 41 % (14/24) bei unipolarer Stimulation. Eine Multivarianzanalyse zeigte jedoch keinen statistisch signifikanten Unterschied zwischen den Gesamt- und Untergruppen. Schlussfolgerung Auch wenn nicht statistisch signifikant, so zeigte sich bei bipolarer Stimulation eine höhere Erfolgsrate als bei der unipolaren Stimulation. Auch bei der Analyse der Subgruppen mit neurogener und nicht neurogener Harntraktfunktionsstörung zeigten sich ähnliche Ergebnisse. Eine größere Serie bei nicht neurogen bedingter Drang/Dranginkontinenz oder Retention kann möglicherweise in Zukunft klären, ob mit der bipolaren Stimulation eine Erfolgsrate auf dem Niveau der zweistufigen Implantation erzielt werden kann.

Background Gathering health information from Internet websites is increasingly utilized by patients. No data exist about hidradenitis suppurativa (HS)-related online health information. Thus, we aimed to study the quality, popularity, readability, and timeliness of the most frequented websites on HS. Methods Google Trends was used to evaluate the public interest in HS. An Internet search on Google was performed for the terms “hidradenitis suppurativa,” “acne inversa,” and “Verneuil's disease.” Readability scores, HONcode quality certification, Alexa popularity rank, and content were assessed. Results Google search queries on HS have steadily risen in the last 10 years. The website analysis revealed 39 unique websites, which were difficult to read. Ten websites (26%) had HONcode quality certification, and the median (IQR) Alexa popularity rank was 48871 (2333–361275). Thirteen websites (33%) yielded disease-specific photos with a median rating between “quite useful” and “uncertain.” A therapy option with adalimumab was mentioned on 11 websites (28%). Conclusions In addition to an increasing interest, we found a broad variation in the quality, readability, popularity, and timeliness of content on HS-related websites. Improvement of the quality and readability of HS-related websites is desirable to potentially raise disease awareness and contribute to an earlier presentation of patients suffering with undiagnosed HS.

BACKGROUND: Fixed and adjustable male slings for the treatment of male urinary stress incontinence became increasingly popular during the last decade. Although fixed slings are recommended for the treatment of mild to moderate stress urinary incontinence, there is still a lack of evidence regarding the precise indication for an adjustable male sling. Furthermore, there is still no evidence that one type of male sling is superior to another. However, both, adjustable and fixed slings, are commonly utilized in daily clinical practice. This current investigation aims to evaluate the differences between fixed and adjustable male slings regarding indications, complication rates and functional outcome in the treatment of male stress urinary incontinence in current clinical practice. METHODS: A total of 294 patients with a fixed and 176 patients with an adjustable male sling were evaluated in a multicenter single arm cohort trial. Data collection was performed retrospectively according the medical record. Functional outcome was prospectively analyzed by standardized, validated questionnaires. Descriptive statistics was performed to present patient characteristics, complication rates and functional outcome. A chi2-test for categorical and independent t-test for continuous variables was performed to identify heterogeneity between the groups and to correlate preoperative characteristics with the outcome. A P value

Introduction Treatment strategy for inoperable and metastatic urothelial carcinoma (mUC) has been revolutionized by the introduction of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) antibodies. During the last 3 decades treatment options were limited to chemotherapy, making further treatment of patients whose disease progressed under ongoing therapy or who were ineligible to receive cytotoxic therapy in the first place, nearly impossible. Evidence acquisition Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting. The objective of this review was to examine and compare the different cohorts and to discuss the quality of the respective studies in order to set up selection criteria for clinical decision making. Evidence synthesis So far pembrolizumab and atezolizumab have demonstrated overall survival (OS) benefit in phase II studies and have shown superiority over standard chemotherapy in phase III studies which has granted them approval in first and second-line treatment setting. Improved OS and durable responses were also seen in phase Ib/II non-randomized, single-arm trials conducted with nivolumab, avelumab and durvalumab and granting accelerated approval for second-line treatment. The huge advantage of immunotherapy and one of the reasons for its overall recognition is its good tolerability profile especially in comparison to chemotherapy. Conclusions Pembrolizumab has to be recommended in second-line therapy due to reporting in a phase III trial and OS survival benefit compared to chemotherapy control group. In cisplatin-eligible and treatment-naive patients with visceral or liver metastases data also slightly favors pembrolizumab rather than atezolizumab.

To compare toxicity and response of docetaxel chemotherapy between metastatic hormone-sensitive prostate cancer (mHSPC) and castration-resistant metastatic prostate cancer (mCRPC) patients of the same therapeutic era for assessing of upfront docetaxel against the benchmark of docetaxel in the castrate resistant stage in the setting outside of clinical trials.A prospectively collected database of real-world prostate cancer patients receiving docetaxel was divided in mHSPC and mCRPC cases and retrospectively analyzed. Principal objectives were toxicity measured by the common criteria of adverse events terminology and response characterized by Prostate specific antigen decline and radiographic progression-free disease at restaging. The prognostic value of suspected variables for grade 3 to 5 toxicity and response was investigated by logistic regression analysis.Of 72 patients 34 (47%) were treated for mHSPC and 38 (53%) for mCRPC. Patients with mCRPC were older and had worse performance status (P0.01). In mHSPC total number of grade 3 to 5 adverse events (24, median 0, interquartile range 0-1) was significantly less than in mCRPC (46, median 1, interquartile range 1-2) (P = 0.01). Multivariable analysis revealed age as independent predictive variable for grade 3 to 5 toxicity (P = 0.03) but not disease stage, Prostate specific antigen predocetaxel, volume of disease, and Eastern Cooperative Oncology Group performance status (P0.05). Objective response was significantly higher in mHSPC compared to mCRPC patients (P0.01). Multivariable analysis confirmed mHSPC stage as independent prognostic factor for radiographic progression free disease at restaging (P0.01).The association of age with toxicity and of mHSPC stage with response resulted in significantly fewer grade 3 to 5 adverse events but higher response rates for upfront docetaxel in mHSPC compared with docetaxel in the later mCRPC stage.

Der wichtigste Risikofaktor fur Brustkrebs ist bei Frauen und Mannern das Alter. Brustkrebs beim Mann ist selten; Untersuchungen zur Fruherkennung werden deshalb nicht empfohlen; diese sind nur bei Veranderungen oder Beschwerden erforderlich (S3-Leitlinie Diagnostik 2018). Fur Frauen liegt das Lebenszeitrisiko fur Brustkrebs bei 12,8 %, d. h. dass jede achte Frau im Verlauf ihres Lebens an Brustkrebs erkrankt. Selten tritt Brustkrebs bei Frauen unter 30 Jahren auf. Der groste Teil der Frauen erkrankt zwischen dem 50. und 70. Lebensjahr; Mitte 60 ist das Risiko am hochsten. Etwa 37 % erkranken nach dem 70. Lebensjahr; Brustkrebs kann jedoch noch bis ins hohe Alter von 90 Jahren und mehr auftreten (Bericht zum Krebsgeschehen in Deutschland 2016).

Background Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce. Patients and Methods Patients’ sample collection was a joint collaboration of the nationwide PANZAR consortium – a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells. Results Of 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2. Conclusion The analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation.

Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has improved the outcome of patients with renal cell carcinoma (RCC), improvement is temporary due to the development of drug resistance. Since many patients encountering resistance turn to alternative/complementary treatment options, an investigation was initiated to evaluate whether the natural compound, sulforaphane (SFN), influences growth and invasive activity of everolimus-resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in vitro. RCC cells were exposed to different concentrations of SFN and cell growth, cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized collagen, chemotactic activity, and influence on surface integrin receptor expression were investigated. SFN caused a significant reduction in both RCCres and RCCpar cell growth and proliferation, which correlated with an elevation in G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B resulted in significantly diminished RCC cell growth. SFN also modulated adhesion and chemotaxis, which was associated with reduced expression of the integrin subtypes α5, α6, and β4. Distinct differences were seen in RCCres adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN) and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes demonstrated divergent action on RCC binding and invasion, depending on RCC cell sensitivity to everolimus. Therefore, SFN administration could hold potential for treating RCC patients with established resistance towards everolimus.

Background Urolithiasis is a widespread disease. Diagnostic imaging plays an important role in the evaluation and management of patients with suspected urolithiasis. Furthermore, modern imaging methods may provide information on stone location, size, fragility and composition aiding the urologist to determine the appropriate treatment modality. Purpose Based on the current literature and guidelines, this review reports on the various new and established diagnostic imaging modalities. Results Ultrasound should always be the initial imaging modality. Following ultrasound, noncontrast CT-principally using a low-dose protocol-is the imaging modality of choice in the evaluation of patients with acute flank pain and suspected urolithiasis. New imaging modalities like dual energy CT, Uro Dyna CT and digital tomosynthesis are currently under investigation but not yet part of daily clinical practice. Magnetic resonance imaging can be used to detect obstruction caused by urinary stones but is not a first-line imaging modality.

Background Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. Methods The records of 413 patients collected by the International Renal Cell Carcinoma–Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan–Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. Results VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. Conclusions In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764–768. © 2016 Wiley Periodicals, Inc.

The objectives of this study are to describe the surgical technique for simultaneous en-bloc robot-assisted radical cystectomy and nephro-ureterectomy, to report its surgical bench marks, and finally, to summarize the current evidence on the procedure. After written informed consent, we prospectively enrolled consecutive patients undergoing simultaneous en-bloc robot-assisted radical cystectomy and nephro-ureterectomy in a prospective institutional database. We performed all procedures with robotic assistance from the DaVinci Si-HD®, a four-arm robotic system. Endpoints included surgery duration, estimated intra-operative blood loss, resection margins, intra-, and post-operative complications. Furthermore, we describe oncological outcome at follow-up. We conducted six (54.4 %) right-sided and five (45.5 %) left-sided nephro-ureterectomies. Urinary diversion consisted in nine (81.2 %) ureterocutaneostomies and in two (18.8 %) ileum conduits. The median surgery duration was 287 min [interquartile range (Q1-Q3) 253-328], thereof 196-min console time (Q1-Q3 158-230). The median-estimated blood loss was 235 mL (Q1-Q3 200-262). We did not register any intra-operative complications or conversions to open surgery. Post-operatively, each one patient suffered a Clavien-Dindo grade 1 (paralytic ileus), grade 2 (blood transfusion), and grade 3 complication (port hernia). After a median follow-up of 7 months (Q1-Q3 4-25), we registered one recurrence, a metachronous transitional cell cancer of the contralateral kidney 24 months after the initial procedure. En-bloc robot-assisted radical cystectomy and nephro-ureterectomy was associated with limited procedure duration, minor blood loss and satisfying intra- and post-operative outcomes.

The prognosis of metastatic or relapsed renal cell carcinoma (RCC) is still very poor, highlighting the need for new treatment strategies. Here, we identify a cooperative antitumor activity of interferon-α (IFNα) together with the Smac mimetic BV6 that antagonizes antiapoptotic IAP proteins. BV6 and IFNα act together to reduce cell viability and to induce apoptosis in various RCC cell lines. Molecular studies revealed that BV6/IFNα co-treatment triggers apoptosis independently of autocrine/paracrine Tumor Necrosis Factor (TNF)α signaling, since the TNFα-blocking antibody Enbrel fails to rescue cell death. Importantly, knockdown of Receptor-Interacting Protein (RIP)1 significantly decreases BV6/IFNα-mediated apoptosis, whereas the RIP1 kinase inhibitor necrostatin-1 (Nec-1) provides no protection. This demonstrates that RIP1 protein is critically required for BV6/IFNα-induced apoptosis, while RIP1 kinase activity is dispensable, pointing to a scaffold function of RIP1. Consistently, BV6 and IFNα cooperate to trigger the interaction of RIP1, Fas-Associated Death Domain protein (FADD) and caspase-8 to form a cytosolic cell death complex that drives caspase activation. Addition of the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) significantly protects RCC cells against BV6/IFNα-induced apoptosis, demonstrating that caspase activity is required for apoptosis. In conclusion, the combination approach of IFNα and BV6 represents a promising strategy for cooperative induction of apoptosis in RCC cells, which warrants further investigation.

To investigate the capacity of stone clearance in common percutaneous nephrolithotomy (PCNL) systems achieved solely by hydrodynamic effects in an in vitro setting.A watertight cylindrical cast with a caliceal void served as an in vitro model. Various instruments for percutaneous renal surgery working with both continuous flow (fCF) and open Rutner sidearm (fCO) were tested. The model was loaded with standardized artificial stone material (2 mm in diameter) to examine stone removal by the vacuum cleaner effect and with sand (0.1-0.5 mm in diameter) to measure the washout effect caused by irrigation backflow. The association between washout of gravel and irrigation pressure was analyzed using ANOVA. Regression analysis was performed to assess the influence of the instruments' hydrodynamic characteristics-effective cross section of the outflow and irrigation flow volume.Provoking the vacuum cleaner effect removal of stones was only effective in fCF but not in fCO instruments. Depending on irrigation pressure, the volumetric flow rate and effective cross section of the outflow clearance of sand could be observed in various medium- and large-sized fCF and fCO instruments, whereas in small-sized systems, clearance effects were negligible. Regression analysis showed clearance of stone dust strongly associated with an instrument's volumetric flow rate.This in vitro study demonstrated that the application of medium- and large-sized fCF PCNL systems removes both "insignificant" stones and dust solely by hydrodynamic effects. Further studies have to show if these effects also occur in the in vivo situation.

Background The cyanogenic diglucoside, amygdalin, has gained high popularity among cancer patients together with, or in place of, conventional therapy. Still, evidence based research on amygdalin is sparse and its benefit controversial. Purpose Since so many cancer patients consume amygdalin, and many clinicians administer it without clear knowledge of its mode of action, current knowledge has been summarized and the pros and cons of its use weighed. Methods A retrospective analysis was conducted for amygdalin relevant reports using the PubMed database with the main search term “Amygdalin” or “laetrile”, at times combined with “cancer”, “patient”, “cyanide” or “toxic”. We did not exclude any “unwanted” articles. Additionally, internet sources authorized by governmental or national institutions have also been included. Sections Individual chapters summarize pharmacokinetics, preclinical and clinical studies and toxicity. Conclusion No convincing evidence showing that amygdalin induces rapid, distinct tumor regression in cancer patients, particularly in those with late-stage disease, is apparent. However, there is also no evidence that purified amygdalin, administered in "therapeutic" dosage, causes toxicity. Multiple aspects of amygdalin administration have not yet been adequately explored, making further investigation necessary to evaluate its actual therapeutic potential.

To analyze efficacy and safety for the ZSI375 artificial urinary sphincter in a multicenter case series. Thirteen male patients with stress urinary incontinence underwent implantation of a ZSI375 artificial urinary sphincter device between 2010 and 2012 in three international continence reference centers. Perioperative characteristics and postoperative complications were analyzed using the Clavien–Dindo scale. Re-hospitalization and explantation rates, and functional outcome were assessed. Inner-group and between-group differences were analyzed using Wilcoxon, Mann–Whitney U, and Fisher’s exact test whenever indicated. Kaplan–Meier analysis was performed to assess device survival. A p value below 0.05 was considered statistically significant. There were no intraoperative complications. Median follow-up was 13.5 months. In this period, four device defects (30.8 %) could be observed, being the main cause for device explantation, followed by device infection (15.4 %), non-resolvable pain (7.7 %), and urethral erosion (7.7 %). There were no Clavien IV or Clavien V complications. Overall explantation rate was 61.5 %. Mean time-to-explantation was 279 ± 308 days. There was no significant influence of previous irradiation and previous invasive incontinence therapy (p = 0.587 and p = 0.685, respectively). Mean daily pad usage decreased from 5.8 ± 1.5 to 2.4 ± 2.1 (p = 0.066). One patient (7.7 %) did not use any pads. Social continence (0–1 pads) was achieved in 15.4 % of the patients. This is the most current study that is investigating the outcome after ZSI375 implantation in a multicenter case series. Based on our results, explantation rates after ZSI375 implantation are high and efficacy rates seem lower than previously described. Addressing this high failure rate, the system has undergone a two-step modification in the meantime.

The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage.

Aims Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed. Main methods LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24 h or 2 weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR–akt signaling axis were analyzed by western blotting. Key findings Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10 mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24 h and 2 weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2 weeks. Significance Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes.

Background/Aims/Objectives: To analyze perioperative complication and short-term explantation rates after perineal or penoscrotal single-cuff and double-cuff artificial urinary sphincter (AUS) implantation in a large middle European multi-institutional patient cohort. Methods: 467 male patients with stress urinary incontinence underwent implantation of a perineal single-cuff (n = 152), penoscrotal single-cuff (n = 99), or perineal double-cuff (n = 216) AUS between 2010 and 2012. Postoperative complications and 6-month explantation rates were assessed. For statistical analysis, Fisher's exact test and Kruskal-Wallis rank sum test, and a multiple logistic regression model were used (p < 0.05). Results: Compared to perineal single-cuff AUS, penoscrotal single-cuff implantation led to significantly increased short-term explantation rates (8.6% (perineal) vs. 19.2% (penoscrotal), p = 0.019). The postoperative infection rate was significantly higher after double-cuff compared to single-cuff implantation (6.0% (single-cuff) vs. 13.9% (double-cuff), p = 0.019). The short-term explantation rate after primary double-cuff placement was 6.5% (p = 0.543 vs. perineal single-cuff). In multivariate analysis, the penoscrotal approach (p = 0.004), intraoperative complications (p = 0.005), postoperative bleeding (p = 0.011), and perioperative infection (p < 0.001) were independent risk factors for short-term explantation. Conclusions: Providing data from a large contemporary multi-institutional patient cohort from high-volume and low-volume institutions, our results reflect the current standard of care in middle Europe. We indicate that the penoscrotal approach is an independent risk factor for increased short-term explantation rates.

Introduction: Prostate carcinoma (PCa) is the most common cancer in men. The therapeutic effect of approved compounds, such as docetaxel, is limited due to the development of therapy resistance, making new treatment options essential. Artesunate (ART), used in Traditional Chinese Medicine, has shown anti-tumor activity in several tumor types. However, little is known about the efficacy of ART on therapy-resistant PCa. Therefore, the impact of ART on docetaxel-resistant PCa cells was investigated. Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, and LNCaP, were exposed to ART [1-100 µM] for 24, 48, or 72 hours. Cells not exposed to ART served as controls. Tumor cell growth, proliferation, cell cycling, and the expression of cell cycle regulating proteins were assessed. Apoptotic, ferroptotic, and necrotic effects were also evaluated. Results: Exposure to ART significantly reduced tumor cell growth and proliferation of parental and docetaxel-resistant PCa cells in a time- and dose-dependent manner. Cell cycle arrest in the G0/G1 phase after 48h exposure to 37.5 µM ART was observed in parental LNCaP and in all three resistant cell lines. The observed changes in cell growth and cell cycle phases were accompanied by marked modulation of cell cycle regulating proteins. Significant apoptotic effects were observed in parental PC3 and both parental and resistant LNCaP, whereas ferroptosis was apparent in parental and resistant DU145 after exposure to ART. Necrotic events were not detectable in the PCa cells after ART exposure. Conclusion: ART induced anti-tumor effects, though differing according to the cell line, were apparent in not only parental but also in docetaxel-resistant PCa cells. Thus, adding ART to standard therapies might be a promising treatment strategy for patients with advanced prostate cancer. Further investigations are necessary to verify our findings. Citation Format: Vitus Braeunig, Patricia Schupp, Sascha Markowitsch, Olesya Vakhrusheva, Holger Erb, Thomas Efferth, Axel Haferkamp, Eva Juengel. Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6327.

5052 Background: Testicular germ cell tumors (TGCT) in clinical stage I (CSI) are tumors confined to the testis without evidence of metastasis. Around 50% of all TGCT patients present with elevated serum tumor markers (TM) such as alpha-feto protein (AFP), beta-humanochoriongonadotropin (ß-HCG) and lactate-dehydrogenase (LDH). After ablatio testis, TMs usually return to normal according to half-life kinetics, however, in clinical stage IS (CSIS) TMs remain elevated or increase after surgery. Follow-up data on CSIS is scarce and our study aims to assess clinical characteristics and oncologic outcomes in a large TGCT cohort. Methods: In this multicenter study we collected data from 5 tertiary referring hospitals in Germany, included patients with CSIS and evaluated TM levels, treatment and the primary outcome relapse-free survival. False CSIS was defined as documented CSIS but TMs that returned to normal after respective half-life kinetics. Differences between predefined groups (chemotherapy, TM, true/false CSIS) was analyzed with fisher’s exact and chi-square test. Results: Overall, 2616 patient data files were analyzed. Forty-three patients (1.6%) were documented as CSIS of which 27 (63%) were true and 16 (37%) false CSIS. Six (14%) had seminomas and 37 (86%) non-seminomas. In the true CSIS group AFP, ß-HCG, AFP plus ß-HCG and LDH were elevated in 13, 6, 3 and 2 cases. Four true CSIS patients received surveillance, 21 had 3x or 2x courses of BEP (bleomycin, etoposide and cisplatin) and 2 carboplatin. Within the false CSIS group, 2 patients were treated with surveillance, 10 received 3x BEP, one 3x PEI (cisplatin, etoposide and ifosfamid) and 3 had carboplatin. Chi-Square test revealed no difference between true or false CSIS classification in respect to application of chemotherapy (any chemotherapy, p = 0.83). Relapse-free survival after 5 and 10 years was 88.9% and 77.8%, respectively. Three patients in the true CSIS group relapsed (2 seminomas had carboplatin, 1 non-seminoma had surveillance). All relapses were treated with 3 courses of BEP with no documented death in the CSIS population. Conclusions: Overall, less than 2% of all TGCT were documented CSIS of which 37% were falsely classified. We report a high proportion of relapse-free survival in CSIS treated with surveillance or BEP with a high heterogeneity in treatment patterns. Correct classification of CSIS remains of critical importance to avoid toxicity for patients that could be safely treated with surveillance.

Testicular germ cell cancer in a metastatic state is curable with a cisplatin‑based first line chemotherapy. However, 10‑15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown. Therefore, the present study performed tissue micro array based analysis of 84 patients with immunohistochemistry of programmed cell death protein 1 (PD‑1), programmed cell death ligand 1 (PD‑L1) and vascular endothelial growth factor receptor 2 (VEGFR2) of testicular cancer and corresponding normal appearing testis tissue, matching the results with clinical data. The results demonstrated that PD‑L1 was significantly upregulated in testicular tumors and that PD‑1 positive cells significantly infiltrated the testicular tumor when compared with normal testicular tissue. VEGFR2 was significantly upregulated in testicular cancer. It was indicated that PD‑1 expressing cytotoxic cells may require pathologic tumor vessels to pass the blood‑testis‑barrier in order to migrate into the tumor. Notably, when matching the clinical data for PD‑1, PD‑L1 and VEGFR2 there were no differences in expression in the different International Germ Cell Cancer Collaborative Group stages of non‑seminoma. These data suggested that the anti‑PD‑1/PD‑L1 immunotherapy and the anti‑angiogenic therapy, sequentially or in combination, may be a promising option in the treatment of testicular cancer.

Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. The present review focusses on the role of the natural compound sulforaphane (SFN) as an anti-tumor agent in urologic cancer. SFN is a natural compound found in cruciferous vegetables from the Brassicaceae family such as broccoli, cauliflower and cabbage. Several epidemiologic and clinical studies have documented chemopreventive properties of SFN, making it an interesting candidate for additive cancer treatment. SFN shows remarkable anti-tumor effects in vitro and in vivo without exerting toxicity. The review summarizes the current understanding of SFN and provides insights into its molecular mode of action with particular emphasis on epigenetic tumor control.

A growing number of patients search for health information online. An early investigation of websites about bladder cancer (BCa) revealed mostly incomplete and particularly inaccurate information. We analyzed the quality, readability, and popularity of the most frequented websites on BCa. An Internet search on www.google.com was performed for the term “bladder cancer.” After selecting the most frequented websites for patient information, HONcode quality certification, Alexa popularity rank, and readability scores (according to US grade levels) were investigated. A 36-point checklist was used to assess the content according to the EAU guidelines on BCa, which was categorized into seven topics. The popularity of the 49 websites analyzed was average, with a median Alexa popularity rank of 41,698 (interquartile range [IQR] 7–4,671,246). The readability was rated difficult with 11 years of school education needed to understand the information. Thirteen (27%) websites were HONcode certified. Out of 343 topics (seven EAU guideline topics each on 49 websites), 79% were mentioned on the websites. Of these, 10% contained incorrect information, mostly outdated or biased, and 34% contained incomplete information. Publically provided websites mentioned more topics per website (median [IQR] 7 [5.5–7] vs. 5.5 [3.3–7]; p = 0.022) and showed less incorrect information (median [IQR] 0 [0–1] vs. 1 [0–1]; p = 0.039) than physician-provided websites. Our study revealed mostly correct but partially incomplete information on BCa websites for patients. Physicians and public organizations should strive to keep their website information up-to-date and unbiased to optimize patients’ health literacy.

Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). Methods: Clinical and histopathological parameters of patients have been prospectively collected within the “PROspective MulticEnTer RadIcal Cystectomy Series 2011”. BMI was categorized as normal weight (2), overweight (≥25–29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. Results: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the ­American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). Conclusions: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled ­accordingly.

Objectives: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus. Patients and methods: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS). Multivariable Cox regression models were used to quantify the effect of multiple covariates. Results: LND was performed in 1,026 patients. In multivariable analysis, the presence of LN metastasis, the number of positive LNs, and LN density were independently associated with cancer-specific mortality (CSM). Clinical node-negative (cN-) disease was documented in 573 patients, 447 of them underwent LND with 43 cN- patients (9.6%) revealing positive LNs at pathology. LN positive cN- patients showed significantly better CSS when compared to LN positive cN+ patients. In multivariable analysis, positive cN status in LN positive patients was a significant predictor of CSM (HR, 2.923; P = 0.015). Conclusions: The number of positive nodes harvested during LND and LN density was strong prognostic indicators of CSS, while number of removed LNs did not have a significant effect on CSS. The rate of pN1 patients among clinically node-negative patients was relatively high, and LND in these patients suggested a survival benefit. However, only a randomized trial can determine the absolute benefit of LND in this setting. Copyright (C) 2018 Elsevier Inc. All rights reserved.

Die Komplementar- und Alternativmedizin (CAM) ist oftmals in die Behandlung von Tumorerkrankungen eingebunden. Tatsachlich ist ihre Popularitat in den letzten Jahrzehnten stetig angestiegen. 80 % der amerikanischen und 50 % der europaischen Tumorpatienten wenden CAM begleitend oder anstelle der konventionellen Therapie an. Dennoch ist das Wissen uber die Wirkeffektivitat von CAM durftig. Die Diskrepanz zwischen Anwendung und tatsachlichem Benefit wird insbesondere beim cyanogenen Diglucosid Amygdalin deutlich, das in den Kernen der Spezies Rosaceae angereichert vorliegt. In den 1970er-Jahren reprasentierte Amygdalin eines der popularsten nicht-konventionellen Antitumor-Verfahren. Alleine im Jahr 1978 konsumierten 70.000 amerikanische Krebspatienten diese Substanz. Ob Amygdalin aber uberhaupt als antitumorales Agens angesprochen werden kann, ist unklar. Befurworter betrachten Amygdalin als naturliches Heilmittel, Gegner hingegen verneinen diese Eigenschaft und warnen vor toxischen Nebeneffekten. Der Ubersichtsartikel fasst das Wissen um diese Substanz zusammen.

Hintergrund Urodynamische Messungen werden zur Diagnostik und Verlaufskontrolle von Funktionsstorungen des unteren Harntraktes eingesetzt. Provokationstests dienen dabei zur Demaskierung von Funktionsstorungen, die in der Standardzystometrie nicht nachweisbar sind. Der Eiswassertest ist ein Provokationstest, um eine neurogene Ursache fur eine Blasenuberaktivitat nachzuweisen.

Jens Mani,1 Eva Juengel,1 Ilhan Arslan,1 Georg Bartsch,1 Natalie Filmann,2 Hanns Ackermann,2 Karen Nelson,3 Axel Haferkamp,1 Tobias Engl,1,* Roman A Blaheta1,* 1Department of Urology, 2Institute of Biostatistics and Mathematical Modeling, 3Department of Vascular and Endovascular Surgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany *These authors contributed equally to this work Objective: Many patients use complementary and alternative medicine (CAM) as primary treatment or symptom relief for a variety of illnesses. This study was designed to investigate the influence of surgical removal of a tumor-bearing urogenital organ on CAM use.Methods: From 2007 to 2011, 350 patients underwent major urological surgery for kidney, prostate, or bladder cancer at the Goethe-University Hospital, Frankfurt, Germany. Data from 172 patients (49%), who returned a questionnaire, were retrospectively evaluated using the hospital information system along with the questionnaire to objectify CAM use 2 years before and after surgery.Results: From the 172 patients returning questionnaires, 56 (33%) used CAM before and/or after surgery and 116 (67%) never used CAM. Of the 56 CAM users, 30 (54%) used CAM presurgery and 53 (95%) used CAM postsurgery, indicating a significant change of mind about CAM use. Patients of German nationality used CAM significantly more than patients of other nationalities. Higher educational status (high-school diploma or higher) was a significant factor in favor of CAM use. The most common type of CAM used before/after surgery was an alternative medical system (63/49%), a manipulative and body-based method (50/19%), and a biological-based therapy (37/32%). Information about CAM, either provided by medical professionals or by other sources, was the main reason determining whether patients used CAM or not.Conclusion: The number of patients using CAM almost doubled after surgical removal of a cancer-bearing organ. Better awareness and understanding of CAM use by medical professionals could improve patient counseling. Keywords: complementary and alternative medicine, surgery, urologic cancer

Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli’s equation provided the explanation of these effects and confirmed our experimental results. We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect.

BAG3 is overexpressed in several malignancies and mediates a non-canonical, selective form of (macro)autophagy. By stabilizing pro-survival Bcl-2 proteins in complex with HSP70, BAG3 can also exert an apoptosis-antagonizing function. ABT-737 is a high affinity Bcl-2 inhibitor that fails to target Mcl-1. This failure may confer resistance in various cancers. Urothelial cancer cells were treated with the BH3 mimetics ABT-737 and (−)-gossypol, a pan-Bcl-2 inhibitor which inhibits also Mcl-1. To clarify the importance of the core autophagy regulator ATG5 and BAG3 in ABT-737 treatment, cell lines carrying a stable lentiviral knockdown of ATG5 and BAG3 were created. The synergistic effect of ABT-737 and pharmaceutical inhibition of BAG3 with the HSF1 inhibitor KRIBB11 or sorafenib was also evaluated. Total cell death and apoptosis were quantified by FACS analysis of propidium iodide, annexin. Target protein analysis was conducted by Western blotting. Knockdown of BAG3 significantly downregulated Mcl-1 protein levels and sensitized urothelial cancer cells to apoptotic cell death induced by ABT-737, while inhibition of bulk autophagy through depletion of ATG5 had no discernible effect on cell death. Similar to knockdown of BAG3, pharmacological targeting of the BAG3/Mcl-1 pathway with KRIBB11 was capable to sensitize both cell lines to treatment with ABT-737. Our results show that BAG3, but not bulk autophagy has a major role in the response of bladder cancer cells to BH3 mimetics. They also suggest that BAG3 is a suitable target for combined therapies aimed at synergistically inducing apoptosis in bladder cancer.

Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUPrGEMCI20), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.

To describe the evolution of the current technique in percutaneous nephrolithotomy (PCNL) with a special focus on access tract closure techniques. A systematic review of outcomes and complications of tubeless PCNL was conducted using the MEDLINE and Pubmed databases between 1976 and 2014. During the past decade, PCNL underwent fundamental modifications due to miniaturization of the instruments and advancements in technique. The routine use of the nephrostomy tube after PCNL has been subsequently questioned. Currently, the nephrostomy tube is increasingly omitted, and the access tract is usually sealed by haemostatic agents. An additionally ureteric stent is commonly inserted at the end of the procedure. However, the application of haemostatic sealants increases the immediate costs significantly. Still there are inconsistent data because of small study populations, lack of randomization, retrospective character and further more heterogeneous surgical techniques. The current body of literature does not provide high-level evidence for the preferred treatment of the access tract in PCNL. However, most authors agree that a tract sealing can be omitted without increasing the risk of complication in uncomplicated procedures.

Robotic assistance simplifies laparoscopic procedures. We hypothesize that robot-assisted sacrocolpopexy is a rapid and safe procedure with satisfying short-term and midterm functional results. After informed consent, we enrolled 101 consecutive patients undergoing sacrocolpopexy at Alfried Krupp Hospital, Essen, Germany. After a median follow-up of 22 months, we assessed midterm functional results as the primary endpoint. Secondary endpoints included surgical duration, blood loss, intraoperative complications, and postoperative complications. We described frequencies as counts (percent) and continuous data as median [interquartile range (Q1–Q3)] or mean [standard deviation (SD)], as appropriate. We enrolled 101 patients. The mean age was 69 years (SD 11); 75 women (74.3 %) had undergone previous abdominal surgery. Among the patients, 95 (94.1 %) presented with anterior vaginal wall prolapse Baden-Walker grade 2–3, 74 (73.3 %) vaginal vault prolapse, and 9 (8.9 %) concomitant rectocele. Fifty (50 %) patients underwent a modified Burch procedure in addition to sacrocolpopexy. The median surgical duration was 96 min (Q1–Q3 83–130). There were six (5.9 %) minor intraoperative complications but no conversions to open surgery. Postoperatively, we registered five (4.9 %) Clavien-Dindo grade I complications, three (3.0 %) grade II complications, and one (1.0 %) grade III complication. After a median follow-up of 22 months (Q1–Q3 12–49), the patients reported significant decreased impact of pelvic organ prolapse (POP) on quality of life as well as bother resulting from POP symptoms. The overall success rate, defined as none or minor impact of POP on quality of life, was 75 %. In this single-surgeon study, robot-assisted sacrocolpopexy was a safe and rapidly performed procedure that achieved good medium-term functional results.

Der Symptomenkomplex der uberaktiven Blase („overactive bladder“, OAB) mit oder ohne Inkontinenz („wet/dry“) hat mit etwa 17% in der europaischen Bevolkerung eine hohe Pravalenz und fuhrt nicht nur zu einem hohen Leidensdruck der Betroffenen, sondern auch zu hohen Kosten fur das Gesundheitswesen. Myogene, urotheliale und neurogene Faktoren fuhren zu noch vielfach unbekannten Veranderungen an Muskel-, Nerven- und Bindegewebe. Zur Definition, Atiologie und Diagnostik der Erkrankung wird hier auf die vorausgegangene CME-Fortbildung „Diagnostik der uberaktiven Blase (OAB)“ verwiesen. In den letzten Jahren ist etwas Bewegung in die Forschung zur OAB gekommen, sei es in Bezug auf die pathophysiologischen Modelle oder hinsichtlich neuer Therapieansatze (Entwicklung neuer Medikamente). Neben altbewahren Substanzen werden zunehmend auch neu zugelassene Wirkstoffe zur Therapie der OAB eingesetzt. Ferner spielen neben der Pharmakotherapie auch nichtmedikamentose Therapieansatze und chirurgische Techniken weiterhin eine wichtige Rolle.

Overactive bladder (OAB) is a symptom complex which is present in approximately 17% of the European population. It is observed in the presence or absence of incontinence (wet or dry) and is associated with a high degree of psychological stress as well as high costs for the healthcare system. Myogenic, urothelial and neurogenic factors lead to frequently unknown changes of muscular, neural and connective tissue. The diagnosis of OAB is empirical and can be used as a basis for initial treatment, while lower urinary tract symptoms have to be evaluated up front. As there are no established biomarkers for OAB, a definitive diagnosis is problematic. It is important to carry out routine diagnostics including a detailed medical history and if needed urodynamic evaluation of the patient. Therapy of OAB will be the topic of a further continuing medical education (CME) article entitled "Therapy of overactive bladder (OAB)".

Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo. The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed. Calcium treated CaSR-transfected 768-O cells showed an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactic cell migration and proliferation was also induced by calcium. The activity of SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR-transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR-transfected 768-O cells showed an increased rate of bone metastasis. The results indicate CaSR as an important component in the mechanism of bone metastasis in RCC. Therefore, targeting CaSR might be beneficial in patients with bone metastatic RCC with a high CaSR expression.

To compare the efficacy and perioperative complications of the AdVanceXP with the original AdVance male sling. We retrospectively enrolled 109 patients with an AdVance and 185 patients with an AdVanceXP male sling. The baseline characteristics and complication rates were analyzed retrospectively. Functional outcome and quality of life were evaluated prospectively by standardized, validated questionnaires. The Chi2-test for categorical and Mann–Whitney U test for continuous variables were performed to identify heterogeneity between the groups. Regarding operation time, there was no significant difference between the slings (p = 0.146). The complication rates were comparable in both groups except for postoperative urinary retention. This occurred significantly more often in patients with the AdVanceXP (p = 0.042). During follow-up, no differences could be identified regarding ICIQ-SF, PGI or I-QoL or number of pad usage. The AdVance and AdVanceXP are safe and effective treatment options for male stress urinary incontinence. However, the innovations of the AdVanceXP sling did not demonstrate a superiority over the original AdVance sling regarding functional outcome.

Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo.

Despite the continuous growth of the internet, little is known about the quality of online information on testicular cancer, the most common solid malignancy in young men. In our study, we analysed the quality, readability and popularity of the most popular websites on testicular cancer. Therefore, we performed a web search for the term “testicular cancer” using www.google.com . Fifty-one websites were evaluated for HONcode quality certification, Alexa Popularity Rank and readability levels. Furthermore, the websites’ content on eight major topics of the current European Association of Urology Guidelines on testicular cancer was assessed. Fourteen (28%) had a HONcode quality certificate and the mean Alexa Popularity Rank of all 51 websites was 54,040 (interquartile range 6648–282,797). Websites were difficult to read requiring 9 years of US school education to properly understand the information. The websites mentioned 80% of the guideline topics on average, revealing “prognosis” (59%) and “follow-up” (57%) as underrepresented subtopics. Furthermore, 12% of all topics were displayed incorrectly, particularly due to wrong information concerning “aetiology” (42%). Sixty percent of the topics were mentioned in an incomplete fashion, with less than half of the websites displaying complete information on “staging” (47%), “diagnostic evaluation” (49%) or “disease management” (45%). In general, online health information concerning testicular cancer is mentioned correctly on most websites. However, improvement regarding readability and completeness of the given information is needed. Nevertheless, highly selected websites on testicular cancer can serve as an appropriate source of patient information.

Antibiotic resistance may lead to increasing infection rates at transrectal prostate biopsy. Local antimicrobial agents might help to reduce bacterial load. The aim of this study was to test the potency of antimicrobial lubricants to reduce local bacterial loads and specifically fluoroquinolone-resistant strains. Overall, 384 prostate biopsy (PBx) patients of a larger prospective randomized trial (n = 1000) were included. Patients were randomized for biopsy with pre-interventional instillation of an antimicrobial lubricant (intervention group n = 256) or with the standard lubricant (control group n = 128). Bacteria were recovered on pre- and post-biopsy rectal swab cultures from both patient groups. Bacterial colonization was semi-quantitatively recorded and analyzed for the presence of ciprofloxacin-resistant isolates. Within the intervention group, where antimicrobial lubricant was instilled for PBx, the post-biopsy bacterial count was statistically significantly lower compared to prior biopsy bacterial count (p

Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen levels in vivo, prolonging survival in mice bearing enzalutamide-resistant MR49F xenografts. Moreover, darolutamide inhibited the transcriptional activity of AR mutants identified in the plasma of CRPC patients progressing on traditional therapies. In particular, darolutamide significantly inhibited the transcriptional activity of the F877L, H875Y/T878A, F877L/T878A, and the previously unreported T878G AR mutants, that transform enzalutamide into a partial agonist. In silico cheminformatics computer modeling provided atomic level insights confirming darolutamide antagonist effect in F877L and T878G AR mutants. In conclusion, our results provide a rationale for further clinical evaluation of darolutamide in enzalutamide-resistant CRPC, in particular in combination with circulating tumor DNA assays that detect AR mutants sensitive to darolutamide, in a precision oncology setting. Patient summary In this study we evaluated the novel drug darolutamide in preclinical models of prostate cancer. We found that darolutamide delays growth of enzalutamide-resistant prostate cancer, in particular in cells with mutated forms of the androgen receptor after previous treatment. Our data supports further evaluation of darolutamide in clinical trials.