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Background: Robot-assisted partial nephrectomy (RAPN) is a challenging procedure that is influenced by a multitude of factors. Objective: To assess the impact of prior surgical experience on perioperative outcomes in RAPN. Design, setting, and participants: In this retrospective multicenter study, results for 2548 RAPNs performed by 25 surgeons at eight robotic referral centers were analyzed. Perioperative data for all consecutive RAPNs from the start of each individual surgeon’s experience were collected, as well as the number of prior open or laparoscopic kidney surgeries, pelvic surgeries (open, laparoscopic, robotic), and other robotic interventions. Intervention: Transperitoneal or retroperitoneal RAPN. Outcome measurements and statistical analysis: The impact of prior surgical experience on operative time, warm ischemia time (WIT), major complications, and margin, ischemia, complication (MIC) score (negative surgical margins, WIT ≤20 min, no major complications) was assessed via univariate and multivariable regression analyses accounting for age, gender, body mass index (BMI), American Society of Anesthesiologists score, PADUA score, and RAPN experience. Results and limitations: BMI, PADUA score, and surgical experience in RAPN had a strong impact on perioperative outcomes. A plateau effect for the learning curve was not observed. Prior laparoscopic kidney surgery significantly reduced the operative time (p

Abstract Background and Aims The transient receptor potential cationic channel ankyrin 1 (TRPA1), a channel protein permeable to most divalent cations, has been suggested to play a role in mechano‐afferent/efferent signaling (including the release of neurotransmitters) in the human urinary tract (bladder, prostate, and urethra). To date, only a few studies have addressed the expression of this receptor in male and female reproductive tissues. The present study aimed to evaluate human seminal vesicles (SVs) for the expression and localization of TRPA1. Methods SV tissue was obtained from 5 males who had undergone pelvic surgery due to malignancies of the prostate or urinary bladder. The expression of messenger ribonucleic acid (mRNA) specifically encoding for the TRPA1 protein was elucidated by means of reverse transcriptase polymerase chain reaction (RT‐PCR). Using immunohistochemical methods, the distribution of TRPA1 was examined in relation to the endothelial and neuronal nitric oxide synthases (eNOS, nNOS) and the neuropeptides calcitonin gene‐related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). Results RT‐PCR revealed signals related to the expected molecular size of 656 bp. Immunohistochemistry demonstrated that TRPA1 is located in nerves running through the smooth muscle portion of the SV. Here, the protein is in part co‐localized with nNOS and CGRP, whereas no co‐localization with VIP was registered. Dot‐like signals specific for TRPA1 were observed in the cytoplasm of epithelial cells lining the lumen of glandular spaces. The epithelial layer also presented staining for eNOS. The smooth musculature appeared free of immunosignals for TRPA1. Conclusion The results convincingly show the expression of TRPA1 in nerve endings as well as in epithelial cells of the SV. Based on its location in epithelial cells, TRPA1 might be involved in the mechanism of the NO/cyclic guanosine monophosphate (GMP)‐mediated signaling and also the control of secretory function (mediated by cyclic GMP) in the human SV.

Abstract Background DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether TACSTD2 is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet. Methods Quantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of TACSTD2 gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of TACSTD2 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of TACSTD2 methylation and TACSTD2 mRNA in KIRC data. Results Higher methylation levels in RCC were significantly associated with advanced disease (p

Abstract Background Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. Methods We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher’s exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. Results UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p

Introduction Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. Materials and methods To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. Results A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. Conclusion While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

PurposeTo assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC).Patients and methodsA total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS).ResultsA total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range,

Background: The introduction of checkpoint inhibitors is a long-awaited new option for a urothelial cancer with a poor prognosis. Apart from clinical studies, the data on real world experience is scarce.Methods: Patients for monotherapy with either Atezolizumab, Nivolumab or Pembrolizumab after chemotherapy were included. Adverse events and immune related adverse events as well as survival data and imaging analyses were recorded in a prospectively designed multi-center data base. Duration of response, progression free survival (PFS), and overall survival (OS) were estimated with the Kaplan-Meier method.Results: A total of 28 patients were included. The median follow-up was 8.0 (range, 0.7–41.7) months. Median PFS was 5.8 (95% CI, 2.3–NA) months. Median OS for all patients was 10.0 (95% CI, 8.0–NA) months. The overall response rate (ORR) was 21.4% (6 out of 28 patients). Adverse events were recorded in 20 (71.4%) of patients. Higher grade adverse events (≥Grade 3) were present in 11 (39.3%) patients. No therapy related deaths occurred during the observation period. A total of 13 (46.4%) patients had adverse events that were considered to be immune related. The most commonly affected organ was the thyroid gland with 21.4% of events.Conclusion: Our real-world clinical series confirms an objective response for about every fifth patient, promising OS and a low incidence for severe adverse events (≥Grade 3).

Introduction After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. Material and methods An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. Results 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers–however, the number of COVID-19 patients and urologists did not reach double digits. Conclusion The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Antimicrobial resistance is a major public health issue caused by antibiotic overuse and misuse. Antimicrobial stewardship (AMS) has been increasingly endorsed worldwide, but its effect has been studied scarcely in urologic settings. A before-after study was performed from 2018 through 2020 to evaluate changes in antimicrobial prescription, resistance rates and clinical safety upon implementation of an AMS audit and feedback program in the Urology Department of a large German academic medical center. The primary endpoints were safety clinical outcomes: the rate of infection-related readmissions and of infectious complications after transrectal prostate biopsies. Resistance rates and antimicrobial consumption rates were the secondary endpoints. The AMS team reviewed 196 cases (12% of all admitted in the department). The overall antibiotic use dropped by 18.7%. Quinolone prescriptions sank by 78.8% (p = 0.02) and 69.8% (p > 0.05) for ciprofloxacin and levofloxacin, respectively. The resistance rate of E. coli isolates declined against ceftriaxone (−9%), ceftazidime (−12%) and quinolones (−25%) in the AMS period. No significant increase in infection-related readmissions or infectious complications after prostate biopsies was observed (p = 0.42). Due to the potential to reduce antibiotic use and resistance rates with no surge of infection-related complications, AMS programs should be widely implemented in urologic departments.

Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA ™ ) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.

Clear cell variants of transitional cell carcinomas (TCC) of the bladder are extremely rare tumors. Only 6 cases have been reported until now. We report of a 67 year old man who presented with fast growing tumor disease. While initial diagnosis showed localized bladder tumor, final histopathology revealed pT4, G3, L1 urothelial carcinoma with clear cell differentiation. No more than 14 weeks after initial diagnosis the patient died from multi-organ failure after unsuccessful salvage laparotomy which showed massive tumor burden within the pelvis and peritoneal carcinosis. This case demonstrated an extremely fast tumor growth. Therefore, patients with clear cell urothelial carcinoma should be treated vigorously and without time delay. We present a case of clear cell variant of TCC which exhibited an extremely aggressive behavior. To our knowledge this is the fifth report of this rare disease.

Abstract Purpose To share our experience using transurethral ultrasound ablation (TULSA) treatment for focal therapy of localized prostate cancer (PCa). Materials and methods Between 10/2019 and 06/2021 TULSA treatment for localized PCa was performed in 22 men (mean age: 67 ± 7 years, mean initial PSA: 6.8 ± 2.1 ng/ml, ISUP 1 in n = 6, ISUP 2 in n = 14 and 2 patients with recurrence after previous radiotherapy). Patients were selected by an interdisciplinary team, taking clinical parameters, histopathology from targeted or systematic biopsies, mpMRI and patients preferences into consideration. Patients were thoroughly informed about alternative treatment options and that TULSA is an individual treatment approach. High-intensity ultrasound was applied using an ablation device placed in the prostatic urethra. Heat-development within the prostatic tissue was monitored using MR-thermometry. Challenges during the ablation procedure and follow-up of oncologic and functional outcome of at least 12 months after TULSA treatment were documented. Results No major adverse events were documented. In the 12 month follow-up period, no significant changes of urinary continence, irritative/obstructive voiding symptoms, bowel irritation or hormonal symptoms were reported according to the Expanded Prostate Cancer Index Composite (EPIC) score. Erectile function was significantly impaired 3–6 months (p

ObjectivesClinical, time-dependent, therapeutic and diagnostic data of patients with LUTS are highly complex. To better manage these data for therapists' and researchers' we developed the application ShinyLUTS.Material and methodsThe statistical programming language R and the framework Shiny were used to develop a platform for data entry, monitoring of therapy and scientific data analysis. As part of a use case, ShinyLUTS was evaluated for patients with non-neurogenic LUTS who were receiving Rezum™ therapy.ResultsThe final database on patients with LUTS comprised a total of 8.118 time-dependent parameters in 11 data tables. Data entry, monitoring of therapy as well as data retrieval for scientific use, was deemed feasible, intuitive and well accepted.ConclusionThe ShinyLUTs application presented here is suitable for collecting, archiving, and managing complex data on patients with LUTS. Aside from the implementation in a scientific workflow, it is suited for monitoring treatment of patients and functional results over time.

ObjectiveRezum is a minimal invasive surgical treatment for patients with lower urinary tract symptoms (LUTS) related to benign prostatic enlargement (BPE). The aim of our study was to assess safety and efficacy of the Rezum procedure in a consecutive series of patients.Material and methodsA retrospective study was performed in a single tertiary care hospital in patients undergoing Rezum procedure between 2018 and 2020. All patients that underwent intervention because of drug-refractory moderate to severe LUTS were assessed. Descriptive outcomes such as symptoms scores (IPSS, IPSS-QoL), peak flow in uroflowmetry (Qmax), post-micturition residual urine volume (PVR) and prostate volume (PVol) were analysed.ResultsIn total, 92 Rezum procedures were performed in the observational period. All interventions were competed without device- or procedure relates adverse events. Patients achieved a significant symptom relief as measured in IPSS (50% reduction, pConclusionRezum therapy is safe and effective and can be considered a viable treatment option for BPH related LUTS.

IntroductionSince the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines.Materials and methodsTo longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses.ResultsA total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate.ConclusionWhile the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

Available tests to detect clinically significant prostate cancer frequently lead to overdiagnosis and overtreatment. Our study assessed the feasibility of combining a urinary biomarker-based risk score (SelectMDx®) and multiparametric MRI outcomes in order to identify patients with prostate cancer on prostate biopsy with increased accuracy and reliability. Samples of 74 men with suspicion of prostate cancer and available multiparametric MRI were analysed in a prospective cross-sectional study design. First-voided urine for determination of HOXC6 and DLX1 mRNA levels was collected after digital rectal examination and prior to MRI/ultrasound fusion-guided prostate biopsy. All multiparametric MRI images were centrally reviewed by two experienced radiologists blinded for urine test results and biopsy outcome. The PI-RADS v2 was used. SelectMDx® score, PI-RADS and Gleason Sore were obtained. Associations between Gleason Score, PI-RADS scores and SelectMDx® were assessed using ANOVA and t-test. Sensitivity and specificity were assessed and evaluated as area-under-the-curve of the receiver operating characteristic. Upon biopsy, 59.5% of patients were diagnosed with prostate cancer, whereby 40.6% had high-grade prostate cancer (GS ≥ 7a). SelectMDx® scores were significantly higher for patients with positive biopsy findings (49.07 ± 25.99% vs. 22.00 ± 26.43%; p < 0.001). SelectMDx® scores increased with higher PI-RADS scores. Combining SelectMDx®, history of prior biopsy with benign histology and PI-RADS scores into a novel scoring system led to significant prostate cancer detection rates with tiered detection rate of 39%, 58%, 81% and 100% for Gleason grade group II, III, IV, and V, respectively. The area-under-the-curve for our novel sum score in receiver operating characteristic analysis was 0.84. The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.

IntroductionAfter the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries.Material and methodsAn email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses.Results27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits.ConclusionThe German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

The relevance of Corticotropin Releasing Hormone (CRH)-system in human malignancies is a question of growing interest. Here we investigated hypermethylation and epigenetic silencing of the CRH-Binding Protein (CRHBP) gene in clear cell renal cell cancer (ccRCC). Relative methylation of the CRHBP CpG island (CGI) was determined in 17 tumor cell lines as well as 86 ccRCC samples and 66 paired normal tissues using pyrosequencing and quantitative methylation specific PCR of bisulfite converted DNA. Results were statistically compared with relative mRNA expression levels of CRHBP and clinicopathological parameters of patients. Re-expression of CRHBP following 5-aza-2´-deoxycytidine treatment was investigated by quantitative mRNA expression analysis. Real-time impedance analysis was applied for analysis of invasiveness of renal tumor cells following si-RNA knockdown of CRHBP expression or ectopic expression of CRHBP. We found the CRHBP CGI to be frequently methylated in tumor cell lines of renal, prostatic, and bladder cancer. Comparison of methylation in normal and paired renal cancer tissue specimens revealed hypermethylation of the CRHBP CGI in tumors (p

Objectives: Whereas local control is often insufficient in conservative management of T4 bladder cancer, neoadjuvant chemotherapy delays definite treatment, which could result in increased therapy-associated morbidity and mortality during the course of the disease. Primary cystectomy has been reported to be associated with a high complication rate and unsatisfactory clinical efficacy. Herein, we report postoperative outcome in 21 T4 bladder cancer patients subjected to primary cystectomy. Materials and Methods: Twenty-one patients underwent radical cystectomy for T4 (T4a/b: 14 and seven cases, respectively) bladder cancer. At the time of surgery, eight patients had regional lymph node metastases (N2: 6; N3: 2). The average age was 64 (52-77) years (≥70 years: n = 7). The postoperative follow-up was 13 (1-36) months for the whole group. Results: Mean duration of postoperative hospitalization was 19 (11-50) days. Whereas 10 patients received no intra - or postoperative blood transfusions, an average number of 3 (1-7) blood units were administered in the remaining cases. The mean postoperative hemoglobin value of patients not receiving any blood transfusions was 10 (8.5 - 11.4) g/dl. Major therapy-associated complications were paresthesia affecting the lower extremities (n = 3) as well as insignificant pulmonary embolism, enterocutaneous fistulation and acute renal failure in one patient, respectively. At the time of data evaluation, 11 patients were still alive after a follow-up of 20 (6-36) months. Four patients ≥70 years at the time of cystectomy were still alive 11, 11, 22 and 31 months following surgery, respectively. Conclusion: Primary cystectomy for T4 bladder cancer is a technically feasible approach that is associated with a tolerable therapy-related morbidity/mortality. Additionally, a satisfactory clinical outcome is observed even in a substantial number of elderly patients.

VEGF-targeted therapy increases both the progression-free (PFS) and overall survival (OS) of patients with metastasized renal cell cancer (mRCC). Identification of molecular phenotypes of RCC could improve risk-stratification and the prediction of the clinical disease course. We investigated whether gene-specific DNA hypermethylation can predict PFS and OS among patients undergoing anti-VEGF-based therapy. Primary tumor tissues from 18 patients receiving targeted therapy were examined retrospectively using quantitative methylation-specific PCR analysis of CST6, LAD1, hsa-miR-124-3, and hsa-miR-9-1 CpG islands. PFS and OS were analyzed for first-line and sequential antiangiogenic therapies using the log rank statistics. Sensitivity and specificity were determined for predicting first-line therapy failure. Hypermethylation of CST6 and LAD1 was associated with both a shortened PFS (log rank p = 0.009 and p = 0.004) and OS (p = 0.011 and p = 0.043). The median PFS observed for the high and low methylation groups of CST6 and LAD1 was 2.0 vs.11.4 months. LAD1 methylation had a specificity of 1.0 (95% CI 0.65-1.0) and a sensitivity of 0.73 (95% CI 0.43-0.90) for the prediction of first-line therapy. CST6 and LAD1 methylation are candidate epigenetic biomarkers showing unprecedented association with PFS and OS as well as specificity for the prediction of the response to therapy. DNA methylation markers should be considered for the prospective evaluation of larger patient cohorts in future studies.

With only 16 cases reported in the literature, the mostly benign granular cell tumour of the urinary bladder is exceptionally rare. We present the case of a 68-year old patient with one of these lesions demonstrating our histological findings including several immunohistochemical stainings used to differentiate between other more common entities.