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PurposeUrinary stone disease is a common disease with a prevalence of 4.7% in Germany. The incidence increased over the last decades, and recurrence rates are up to 50% in the first 5 years after diagnosis. Adequate preventive measures can avoid up to 46% of stone recurrences. These numbers outline the importance of prevention. Especially among high-risk stone formers, specific diagnostics and measures are required. Published data indicate the divergence between the importance of prevention and its implementation in everyday clinical practice. This is the first survey among German urological departments highlighting medical care concerning the prevention of recurrent urinary stone disease, identifying challenges and providing recommendations for improvements.MethodsTwo hundred and seventy urological hospital departments in Germany were anonymously surveyed about measurements to prevent recurrent stone disease. The questionnaire comprised 23 items dealing with diagnostics, counselling, knowledge among doctors concerning preventive measures and difficulties in preventing recurrent urinary stone disease.ResultsSixty-three urological departments (23.8%) answered the survey. The majority perform stone analysis at first and repeat events. Most patients with urinary stone disease receive general advice on preventive measures during their hospitalization. General recommendations focus on fluid intake and lifestyle changes. However, specific diets are infrequently recommended by inpatient urologists. Diagnostics to identify high-risk stone formers are mostly insufficient, and guideline-compliant urine tests are uncommon.ConclusionThe quality of secondary prevention needs to improve considerably. The focus should be put on identifying high-risk stone formers and offering those patients specific counselling. Furthermore, general advice on dietary recommendations should be extended.

PurposeTo evaluate early continence of patients who underwent inpatient rehabilitation after radical cystectomy (RC) and orthotopic bladder substitution (ONB).MethodsWe conducted a retrospective analysis on the data of 283 patients who underwent a three weeks inpatient rehabilitation after RC and ONB for bladder cancer between January 2016 and July 2017. All patients were treated with a special multimodal continence therapy. The continence status was evaluated by measuring urine loss by a 24-h pad test and urine volume on uroflowmetry at the beginning (T1) and at the end (T2) of inpatient rehabilitation. Multivariate linear regression analysis was performed to identify independent predictors of urine loss.ResultsMedian patient age was 63 years. NS was documented for 142 patients (50.2%). Median urine loss decreased significantly (p < 0.001) in the 24-h pad test, from 442 gm at T1 (median 29 days after surgery) to 88 gm at T2 (median 50 days after surgery). Urine volume increased significantly (p < 0.001) from a median of 78 ml at T1 to a median of 157 ml at T2. Age (p = 0.002), diabetes (p = 0.031), obesity (p = 0.003), and nerve sparing (p = 0.011) were identified as independent predictors for urine loss at the end of inpatient rehabilitation.ConclusionContinence improved significantly during the three weeks of inpatient rehabilitation. Younger age, the absence of diabetes or obesity, and NS resulted in better continence in the early postoperative period after ONB.

Treatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy. We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. We found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058). Using validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

To evaluate factors affecting the outcomes of short-term Mono-J insertion for 6 h following ureteroscopic stone removal. Patients treated with a Mono-J for 6 h after ureterorenoscopy and stone removal were analysed. FaST 1 and 2 (Fast Track Stent Studies), two consecutive single academic centre studies, were conducted between August 2014 and April 2018. In each study, we randomized patients with renal or ureteral calculi to two groups before ureterorenoscopy. FaST 1 compared a Mono-J insertion for 6 h versus Double-J insertion for 3–5 days after ureterorenoscopy. FaST 2 compared a Mono-J insertion to a tubeless procedure in the same clinical setting. All patients were pre-stented for 3–5 days before URS. The study endpoint was stent-related symptoms as assessed by a validated questionnaire (USSQ). Results were stratified by clinical parameters, stone characteristics and operation details. 108 of 156 initially randomized patients undergoing ureterorenoscopy were included. USSQ scores covering the time 3–5 weeks after stone removal showed a significantly reduced urinary symptoms and pain index compared to the scores before ureterorenoscopy. USSQ results before and after stone removal did not correlate with stone size or operation time and did not differ significantly depending on stone localization, the treating endourologist, or ureterorenoscopic device used (p > 0.05). Six patients (5%) required reintervention. Following secondary ureterorenoscopy and ureteral drainage with a Mono-J for 6 h, quality of life is independent of stone size and localization, operation time, the treating endourologist, and the URS device used.

Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4. In addition, we describe the anti-apoptotic protein BCL2 as a target of miR-205, relevant for prostate cancer due to its role in prognosis of primary tumours and in the appearance of androgen independence. The repression of BCL2 by miR-205 was confirmed using reporter assays and western blotting. BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3). Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap. MiR-205 also inhibited proliferation in these cell lines.

To compare the outcome of a short-term insertion of a mono-J catheter for 6 h following ureteroscopic stone removal to a conventional double-J catheter. This single-center academic study (Fast Track Stent study 3) evaluated stenting in 108 patients with urinary calculi after ureterorenoscopy. Patients were prospectively randomized into two study arms before primary ureterorenoscopy: (1) mono-J insertion for 6 h after ureterorenoscopy and (2) double-J insertion for 3–5 days after ureterorenoscopy. Study endpoints were stent-related symptoms assessed by an ureteral stent symptom questionnaire (USSQ) and reintervention rates. Stone sizes and location, age, operation duration, BMI, and gender were recorded. Of 67 patients undergoing ureterorenoscopy, 36 patients were analyzed in the double-J arm and 31 patients in the mono-J arm. Mean operation time was 27.5 ± 1.3 min versus 24.0 ± 1.3 min, and stone size was 5.2 mm versus 4.5 mm for mono-J versus double-J, respectively (p = 0.06 and p = 0.15). FaST 3 was terminated early due to a high reintervention rate of 35.5% for the mono-J group and 16.7% for the double-J group (p = 0.27). One day after ureterorenoscopy, USSQ scores were similar between the study arms (Urinary Index: p = 0.09; Pain Index: p = 0.67). However, after 3–5 weeks, the Pain Index was significantly lower in those patients who had a double-J inserted after ureterorenoscopy (p = 0.04). Short-term insertion of mono-J post-ureterorenoscopy results in similar micturition symptoms and pain one day after ureterorenoscopy compared to double-J insertion. The reintervention rate was non-significant between the treatment groups most likely due to the early termination of the study (p = 0.27). Ethics approval/Trail Registration: No. 18-6435, 2018

Background For more than 80 years, cystoscopy has been the gold standard for identification of urothelial carcinoma (UCa). Because of many factors, such as pain of the patients during this procedure or the costs involved, non-invasive detection of UCa remains a challenge. Herein, we verify our previously identified urinary biomarkers C-X-C Motif Chemokine Ligand 16 (CXCL16) and transforming growth-factor beta induced protein (TGFBI) on the protein level as well as the CpG sites ALOX5, TRPS1 and an intergenic region on Chromosome 16 on DNA methylation level in an independent cross-sectional study. Methods We collected N = 1119 urines from individuals coming to urological and gynecological check-ups, follow-up care or patients suspicious for UCa or already diagnosed for different urologic or gynecologic cancer entities. We performed methylation analysis of various CpG sites with DNA isolated from urine sediment and quantified the concentration of the protein markers CXCL16 and TGFBI in the corresponding urine supernatant using ELISA. We tested for patient-group differences with two-sided Wilcoxon rank sum tests and examined the performance with receiver operating characteristic curves. For verification, we analyzed the marker performance with previously set cutoff-values and marker combinations with established and experimental algorithms (with logical OR-conjunction, iterative threshold-based biomarker and score combining algorithm “PanelomiX”). Results Evaluation confirmed that our previously identified protein and DNA methylation biomarkers can distinguish UCa from frequent urological and gynecological cancers. CXCL16 and TGFBI discriminated UCa cases with a sensitivity of 31% and 56% and a specificity of 94% and 85%, respectively. Combining methylation markers resulted in UCa detection in men with a sensitivity of 54% and a specificity of 94%. Extending analysis by combining all methylation and protein markers (up to five markers in total) yielded a convincingly high specificity of 97% at a sensitivity of 72% for the identification of UCa patients within a heterogeneous collective of cancer-free individuals and patients suffering from urological or gynecological cancers. Conclusion Combining various biomarkers at protein and DNA level demonstrates a new option of non-invasive UCa diagnosis in urine, and thus might help to reduce the number of unnecessary cystoscopies, especially in patients without a history of UCa.

Background & Objectives: Current guidelines recognize a subgroup of favorable intermediate-risk (FIR) ISUP grade group (GG) 2 prostate cancer (PCa) that may be eligible for active surveillance (AS). However, upgrading and upstaging to more aggressive disease are frequently observed. We aimed to identify risk factors for adverse pathology in this cohort to better define clinical scenarios where AS may need to be reconsidered. Methods: We retrospectively analyzed 170 patients diagnosed with ISUP GG2 PCa by multiparametric MRI (mpMRI)/TRUS fusion biopsy, all treated with radical prostatectomy (RP). Patients with FIR disease were evaluated for upstaging to ≥pT3 or upgrading to ISUP GG of ≥3 at RP. Multivariable logistic regression identified predictors of adverse pathology. Key Findings and Limitations: Among 170 FIR patients, median PSA was 5.6 ng/mL. Most had PI-RADS 4 (57%) or 5 (20%) lesions; 13% were diagnosed by systematic biopsy only. At RP, 28% showed adverse pathology, including 5 patients (2.9%) with lymph node metastases. Independent predictors were a PI-RADS Score of ≥4, PSA of >7 ng/mL, and clinical T-stage on digital rectal examination. Conclusions and Clinical Implications: Nearly 1/3 of FIR PCa patients were upstaged to high-risk PCa at RP. Based on these findings, AS in clinical practice should only be considered after thorough patient counseling and performed using a stringent follow-up and staging regimen to minimize the risk of further disease progression. A key limitation is the lack of the percentage of Gleason pattern 4.

BackgroundThe impact of variant histologies on overall survival (OS), as well as their influence on the response to neoadjuvant and adjuvant chemotherapy (AC) is well studied in patients diagnosed with bladder cancer. However, little is known about tumors with variant histologies of the upper urinary tract. The objective of this study was to assess the survival of the predominant variant histologies of tumors of the renal pelvis (RPT) after surgical intervention, and to examine the influence of AC on the OS of the different variant histologies.MethodsWe identified 21,318 patients with RPT undergoing surgical intervention using the National Cancer Database for the period 2004–2015. We employed multivariable Cox proportional hazards regression models and Kaplan–Meier curves to evaluate the OS according to variant histology. Separate multivariable Cox regression models were used to assess the specific effect of AC on OS of the histological subgroups.ResultsThe majority of patients were diagnosed with pure urothelial carcinoma (PUC) (96.1%). Overall, 826 patients were diagnosed with variant histologies (adenocarcinoma N = 298, squamous cell carcinoma N = 291, sarcomatoid N = 137, others N = 100). Compared to PUC, adenocarcinomas showed longer OS (HR 0.76, 95% confidence interval (CI) 0.62–0.94, p = 0.01), while sarcomatoid tumors had shorter OS (HR 1.59, 95% CI 1.12–2.26, p = 0.011). A subgroup analysis of patients undergoing AC showed a survival benefit in patients with PUC (HR 0.81, 95% CI 0.73–0.9, p < 0.001).ConclusionWe found that variant histologies of upper urinary tract carcinomas exhibit different survival rates and that AC was only associated with an OS benefit in patients with PUC.

Purpose To evaluate treatment variables for early urinary continence status 6 weeks following radical prostatectomy. Methods In this retrospective analysis, 4,028 consecutive patients underwent open radical retropubic (RRP) or robot-assisted transperitoneal prostatectomy (RARP) at a single academic institution (07/2003–07/2013). After discharge, patients were offered 3-week treatment in a rehabilitation facility. Patients who opted for rehabilitation ( n  = 2,998, 74.4 %) represent our study cohort. Exclusion criteria were acute urinary retention after catheter removal ( n  = 55, 1.4 %), incomplete datasets ( n  = 50, 1.2 %) or refusal of rehabilitation ( n  = 925, 23.0 %). Results of urinary continence were evaluated from final rehabilitation reports. Twenty-two clinical and oncological variables were statistically analysed in uni- and multivariable analyses to determine whether they were associated with early urinary continence status six weeks after radical prostatectomy. Odds ratios and 95 % CI as well as p values were calculated. A p level of 0.05 was considered as significant. Results Six weeks after surgery, 1,962 (65.4 %) patients were continent (≤1 pad/day) and 1,036 (34.6 %) patients were considered incontinent. Age, clinical stage, PSA, ASA score, prior TURP, seminal vesicle invasion, Gleason score, nerve-sparing status, intraoperative blood loss, catheterisation time, OR time, surgical caseload >1,000 and the surgeon were associated with continence status on univariable analysis ( p  < 0.05). On multivariable analysis, nerve-sparing procedure (NS), clinical stage, individual surgeon, patient age, surgical procedure (RARP vs. RRP) and duration of catheterisation were independent predictors ( p  < 0.05) of incontinence status. Conclusions Strategies that can ensure NS procedures and early catheter removal should be applied to enable early recovery of urinary continence.