Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.

Background: Worldwide, urothelial carcinoma (UC) is a common cause of morbidity and mortality. In particular, the incidence of bladder cancer varies widely across Europe; Germany has the ninth highest international age-standardized incidence. For advanced UC or metastatic UC (mUC), platinum-based combination chemotherapy is the standard first-line (1L) treatment; however, there is wide heterogeneity of second-line (2L) treatments, ranging from vinflunine in parts of Europe to taxanes and other agents elsewhere in Europe, in the United States and globally. Limited data exist on treatment patterns and outcomes in patients with advanced UC or mUC in the routine clinical setting in Germany. The objective of this study was to describe clinical characteristics, treatment patterns and subsequent outcomes in this setting.Methods: This retrospective observational cohort analysis evaluated 1L and 2L treatment patterns and overall survival (OS) in patients aged ≥18 years with advanced UC or mUC (T4b, N2-3 and/or M1) at office-based urology and academic as well as nonacademic urology clinics throughout Germany between 1 November 2009 and 2 June 2016. Data were obtained through the GermanOncology database and additional treatment centers using similar electronic case report forms.Results: Among the 435 patients included in the analysis, 435 received 1L treatment and 125 received 2L treatment. Median age at start of 1L treatment was 69 years, 75% of patients were male, 75% were current or ex-smokers, 15% had hemoglobin <10 g/dL and 44% had creatinine clearance<60 mL/min/1.73; proportions were similar with 2L treatment. Cardiovascular disease was the most frequently reported comorbidity (65%), followed by diabetes (19%). Most patients (77%) received 1L platinum-based combination treatment (most commonly gemcitabine + cisplatin, 83%). Of those treated with 2L treatment, 66% received a single agent (most commonly vinflunine, 71%). Median OS (95% CI) with 1L treatment was 16.1 months (13.7-19.2) overall and 17.7 months (14.4-24.2) with 1L cisplatin + gemcitabine. In the 1L setting, 12-month OS was 61%, 24-month OS was 39% and 36-month OS was 26%. Median (95% CI) OS with 2L treatment was 9.2 months (5.5-11.6) overall and 5.9 months (4.1-12.6) with 2L vinflunine. In the 2L setting, OS rates for the same time periods were 40%, 22% and 8%, respectively. Median (95% CI) progression-free survival was 7 months (6.4-8.1) and 4 months (3.0-4.8), respectively, in the 1L and 2L settings. Objective response rates were 34% in the 1L setting and 14% in the 2L setting. No difference in OS by sex or smoking status was noted. Patients with or without renal impairment had a 12-month OS of 54% or 69%, respectively. OS at 12 months was 63% among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 vs 53% among patients with an ECOG PS of ≥2. Cox regression analysis found no difference in OS between vinflunine and other 2L treatments (P = 0.69).Conclusions: This study provides a contemporary multicenter assessment...

PurposeSentinel lymph node (LN) dissection (sLND) using a magnetometer and superpara-magnetic iron oxide nanoparticles (SPION) as a tracer was successfully applied in prostate cancer (PCa). The feasibility of sentinel LN (SLN) visualization on MRI after intraprostatic SPION injection has been reported. In the present study, results of preoperative MRI identification of SLNs and the outcome of subsequent intraoperative magnetometer-guided sLND following intraprostatic SPION injection were studied in intermediate- and high-risk PCa.Patients and methodsA total of 50 intermediate- and high-risk PCa patients (prostate-specific antigen >10 ng/mL and/or Gleason score ≥7) scheduled for radical prostatectomy with magnetometer-guided sLND and extended pelvic LND (eLND), were included. Patients underwent MRI before and one day after intraprostatic SPION injection using T1-, T2-, and T2*-weighted sequences. Diagnostic rate per patient was established. Distribution of SLNs per anatomic region was registered. Diagnostic accuracy of sLND was assessed by using eLND as a reference standard.ResultsSPION-MRI identified a total of 890 SLNs (median 17.5; IQR 12–22.5). SLNs could be successfully detected using MRI in all patients (diagnostic rate 100%). Anatomic SLN distribution: external iliac 19.2%, common iliac 16.6%, fossa obturatoria 15.8%, internal iliac 13.8%, presacral 12.1%, perirectal 12.0%, periprostatic 3.7%, perivesical 2.3%, and other regions 4.4%. LN metastases were intraoperatively found in 15 of 50 patients (30%). sLND had a 100% diagnostic rate, 85.7% sensitivity, 97.2% specificity, 92.3% positive predictive value, 94.9% negative predictive value, false negative rate 14.3%, and 2.8% additional diagnostic value (LN metastases only outside the eLND template).ConclusionMR scintigraphy after intraprostatic SPION injection provides a roadmap for intraoperative magnetometer-guided SLN detection and can be useful to characterize a reliable lymphadenectomy template. Draining LN from the prostate can be identified in an unexpectedly high number, especially outside the established eLND template. Further studies are required to analyze discordance between the number of pre- and intraoperatively identified SLNs.

IntroductionPenile carcinoma has an incidence of 4,000 cases in Europe. The therapy and prognosis depend decisively on the lymph node status. Lymph node metastases are detected in 23–65% cases depending on the histopathological pattern. Due to improved diagnostic methods an early detection of tumor stage is possible. Multimodal therapeutic concepts can offer curability for a subset of patients, even those suffering from advanced disease.Material and methodsCurrent data on penile cancer based on a selective review of the literature by PubMed and the EAU guidelines 2009.ResultsInvasive diagnostic tools, such as fine–needle biopsy (FNB) and dynamic sentinel node biopsy (DSNB), improved the diagnosis of lymph node status considerably and reduced the morbidity in specialized centers. The application of 18F–FDG–PET/CT for metastases detection needs further evaluation due to inconsistent results. Inguinal lymphadenectomy is the therapeutic standard in case of metastases proof. It was possible to reduce the complications due to the new modified operation techniques. Patients with extended lymph node and distant metastases have a poor prognosis. Different systemic polychemotherapy regimes are applied currently and are associated with poor outcome (response rates <50%) and high morbidity. Neoadjuvant chemotherapy is recommended in patients with unresectable and relapsing lymph node metastases.ConclusionsCurrently, inconsistent therapy regimens are applied for metastatic penile cancer. Standardization is urgently needed through the development of high–quality studies and long–term registers in order to lower the morbidity and increase the efficiency of diagnosis and therapy.

Introduction. Aim of this study was to assess the safety and efficacy of injection of autologous muscle-derived cells into the urinary sphincter for treatment of postprostatectomy urinary incontinence in men and to characterize the injected cells prior to transplantation. Methods. 222 male patients with stress urinary incontinence and sphincter damage after uroloical procedures were treated with transurethral injection of autologous muscle-derived cells. The transplanted cells were investigated after cultivation and prior to application by immunocytochemistry using different markers of myogenic differentiation. Feasibility and functionality assessment was achieved with a follow-up of at least 12 months. Results. Follow-up was at least 12 months. Of the 222 treated patients, 120 responded to therapy of whom 26 patients (12%) were continent, and 94 patients (42%) showed improvement. In 102 (46%) patients, the therapy was ineffective. Clinical improvement was observed on average 4.7 months after transplantation and continued in all improved patients. The cells injected into the sphincter were at least ~50% of myogenic origin and representative for early stages of muscle cell differentiation. Conclusions. Transurethral injection of muscle-derived cells into the damaged urethral sphincter of male patients is a safe procedure. Transplanted cells represent different phases of myogenic differentiation.