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Background: This study is aimed to analyze the effect of social distancing on functional outcomes (potency, continence recovery, and quality of life) on patients undergoing open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) during the COVID-19 pandemic., Materials and Methods: We retrospectively assessed functional outcomes of 55 consecutive patients who underwent radical prostatectomy during the COVID-19 pandemic (group A: 12 ORP and 15 RARP) and compared these data with patients from the previous year (group B: 13 ORP and 15 RARP). Propensity-score matching was performed to analyze variables associated with potency, continence recovery and compared between the groups at 1 and 3months., Results: Patients from group A were less interested in postsurgical rehabilitation compared to those from group B (95.7% vs. 56.2%, p   =  0.042). Continence recovery among group B patients also tended to be higher for RARP (p   =  0.06) and ORP (p   =  0.08) at 1 month, although statistical significance was not reached. The cumulative continence recovery at 3 months among group B patients was higher and statistically significantly advantageous for RARP (p   =  0.00) and ORP (p   <  0.01). Potency rates among younger group B patients following bilateral nerve-sparing procedures were statistically significantly advantageous for RARP (p   =  0.026) and ORP (p   =  0.011)., Conclusions: Our results highlight the large impact of the COVID-19 pandemic on functional outcomes following radical prostatectomy. Future design and planning of home-based models for improved post-operative care should consider this evidence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the efficacy and safety of desmopressin on frequency and urgency in female patients with overactive bladder (OAB) and nocturia., Methods: A selective database search was conducted to validate the effectiveness of desmopressin in patients with OAB and nocturia. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were utilised. The meta-analysis included 378 women (five studies) with OAB. The clinical outcomes and adverse events were analysed., Results: The treatment strategy of all the studies included can be divided into three categories: (1) The effect of desmopressin compared with baseline, (2) desmopressin compared with placebo, and (3) desmopressin and anticholinergic combination versus desmopressin monotherapy. There was a significant (50%) reduction in nocturia and urgency episodes after using desmopressin alone. Combined desmopressin and anticholinergic led to a decrease in the frequency of nocturia voids when only using anticholinergic (65% vs. 33.2%). The time increased in the middle to the first nightly voids in the combination arm (65.11 min; p =0.045). The mean incidence (standard deviation) of leak-free episodes was higher under desmopressin than under placebo in the first 4 h (62% [35%] vs. 48% [40%]) and in the first 8 h (55% [37%] vs. 40% [41%]). The safety profile was comparable between treatments., Conclusion: Available data indicate that desmopressin is efficacious in significantly reducing nighttime urine production, episodes of nocturia, and urgency episodes. The affectivity of the combination therapy was very high with least side effects for the treatment of OAB/nocturnal polyuria., Competing Interests: The authors declare no conflict of interest., (© 2022 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Background: SelectMDx is a urinary biomarker test for determining prostate cancer risk., Aim: In a group of patients with a biopsy proven prostate cancer (PCa) who had undergone a multi parametric Magnetic Resonance Imaging (mpMRI) and urinary biomarker test with SelectMDx, we studied the additive value of SelectMDx to mpMRI and correlated that to the radical prostatectomy histology., Methods and Results: Thirty-nine consecutive patients with a positive prostate biopsy were included in the study. They all had mpMRI and SelectMDx and underwent a radical prostatectomy. Overall, the mpMRI showed a PIRADS ≤3 lesion in seven cases out of the 39 patients. Significant lesions (PIRADS ≥4) were found in 32 cases (82%), that is, in 17 cases a PIRADS 5 lesion and in 15 cases a PIRADS 4 lesion. The mpMRI missed significant PCa in seven cases (18%) who had a PIRADS ≤3 lesion but had a significant PCa on final histology after RP. In our study, the positive predictive values of mpMRI were 97% and that of the SelectMDx was 100%., Conclusion: In this real-life selected group of consecutive patients with a confirmed positive PCa biopsy and available mpMRI, the liquid biopsy test with SelectMDx, did not provide an additional information about the PCa clinical significance. The addition of SelectMDx was only found valuable in those patients who had a very high-risk PCa (ie, GS ≥8) who had a positive SelectMDx test outcome despite of a negative mpMRI outcome., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.

In the future, precision medicine with agents targeting specific genetic alterations will play an important role in bladder cancer. This includes both single genetic alterations (e.g. FGFR3) and gene panel analyses in patients with no further therapeutic options, rare cancer subtypes or unusual clinical courses. These molecular analyses can be carried out on formalin-fixed paraffin-embedded tumor samples and the results should be discussed in interdisciplinary molecular tumor boards in order to either recommend approved targeted therapies or suggest patients for molecular-based clinical trials, compassionate use programs or off-label use of drugs. The remuneration of molecular diagnostics is largely well-represented for the outpatient sector in Germany; however, the covering of treatment costs must currently be approved by the health insurances., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms., Methods: The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran., Results: None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039)., Conclusion: Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients., (© 2021. The Author(s).)

Background: Scientific congresses are an important medium for presenting recent clinical findings. Publication of abstracts allows wider dissemination. Objectives: To determine the publication rates of prostate cancer abstracts presented at the annual congress of the European Association of Urology (EAU). Design, Setting, and Participants: All abstracts with the term prostate cancer or carcinoma presented at the congress of the European Association of Urology from 2015 to 2018 were analyzed. We captured their publication rate, journal impact factor and time to publication. Moreover, we formulated a scoring system to determine the grade of discrepancy between the conclusions mentioned in the congress abstract and published abstract. Results: A total of 834 abstracts presented at EAU annual meeting included prostate cancer or carcinoma in their title. We recorded a publication rate of 56.8% with 474 of the 834 abstracts being published with a mean time of 12.5 months. Conclusion: Approximately, 57% of the prostate cancer abstracts presented at the EAU congress are published in peer reviewed journals. This acceptance rate indicates the high distribution and dissemination of these abstracts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ataei, Bach, Javan, Vögeli, Grafe and Rahnama'i.)

Objective: To evaluate the safety and efficacy rate of polyvinylidene fluoride (PVDF) slings in the treatment of female stress urinary incontinence (SUI)., Material and Methods: A prospective pilot study was conducted with women with SUI who underwent PVDF slings. Data regarding subjective (International Consultation on Incontinence Questionnaire - Urinary Incontinence [ICIQ-UI] and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]) and objective (stress test and bladder diary) outcomes and complication rates were evaluated. Primary outcomes were objective (negative pad and stress test) and subjective (no leakage episodes) success after a median follow-up of 24 months., Results: PVDF slings demonstrated a high level of satisfaction with objective cure (transobturator 90% compared with retropubic 100%, P = .90), urgency to urinate, frequency of de novo incontinence (transobturator 90% compared with retropubic 80%, P = .85), ability of physical and sexual activity (transobturator 90% compared with retropubic 100%, P = .90). The multivariate logistic regression model for satisfaction was associated with overall treatment success (odds ratio [OR] = 3.55, 95% confidence interval [CI] 2.32-6.1), greater reduction in ICIQ-UI (OR = 0.85; 95% CI 0.78-1.85) and ICIQ-OAB (OR =0.99; 95% CI 0.89-1.78). The total Female Sexual Function Index (FSFI) score for both groups was 19.3 ± 1.2 and 20.7 ± 1.8, statistically significant when compared with perioperative FSFI score 16.7 ± 1.1 and 17.6 ± 1.4 (P < .001)., Conclusion: PVDF mid-urethral slings are safe with clinically efficacies at 3, 6, 12, and 24-month follow-up for the treatment of SUI. The high level of satisfaction seen after PVDF sling procedures is associated with objective improvement of SUI and fewer slings related complications. Further studies using larger sample sizes with longer and comparative clinical follow-up are required.

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs., Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set., Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set., Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

Purpose: Until recently, the urine of healthy individuals was assumed to be sterile. However, improvement of bacterial detection methods has debunked this assumption. Recent studies have shown that the bladder contains microbiomes, which are not detectable under standard conditions. In this review, we aimed to present an overview of the published literature regarding the relationship between urinary microbiota and functional disorders of the genitourinary system., Methods: We searched Medline, PubMed, Embase, The Cochrane library and Scopus to identify RCTs published, with MeSH and free keywords including microbiota, bladder pain syndrome, prostatitis, kidney stone disease, and bladder cancer until September 2020. Randomized controlled trials investigating microbiome and lower urinary tract symptoms were included. Non-randomized trials, cross-over trials and pooled studies were excluded. The articles were critically appraised by two reviewers., Conclusion: The urine microbiome is a newly introduced concept, which has attracted the attention of medical researchers. Since its recent introduction, researchers have conducted many fruitful studies on this phenomenon, changing our perspective toward the role of bacteria in the urinary tract and our perception of the genitourinary system health., Result: A deeper understanding of the urinary microbiome can help us to develop more efficient methods for restoring the microbiota to a healthy composition and providing symptom relief. Modification of the urinary microbiome without antibiotic use can be a possible venue for future research.

Background: Bladder cancer is highly related to immune cell infiltration. This study aimed to develop a new classification of BC molecular subtypes based on immune-cell-associated CpG sites., Methods: The genes of 28 types of immune cells were obtained from previous studies. Then, methylation sites corresponding to immune-cell-associated genes were acquired. Differentially methylated sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylated sites was performed to divide the sites into several subtypes. Then, the potential mechanism of different subtypes was explored., Results: Bladder cancer patients were divided into three groups. The cluster 3 subtype had the best prognosis. Cluster 1 had the poorest prognosis. The distribution of immune cells, level of expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC co&#95;inhibition, APC co&#95;stimulation, HLA, MHC class&#95;I, Type I IFN Response, Type II IFN Response, and DNAss presented significant differences among the three subgroups. The distribution of genomic alterations was also different., Conclusions: The proposed classification was accurate and stable. BC patients could be divided into three subtypes based on the immune-cell-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were varied among the three subgroups. High-level immune infiltration was correlated with high-level methylation. The lower RNAss was associated with higher immune infiltration. The study of the intratumoral immune microenvironment may provide a new perspective for BC therapy.

Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative "Achilles heel" of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.

Objective: To evaluate the current state, therapeutic benefit and safety of urethral injection of autologous stem cells for the treatment stress urinary incontinence (SUI)., Materials and Methods: A selective database search of PubMed, the Excerpta Medica dataBASE (EMBASE), Cochrane Library and Google Scholar was conducted to validate the effectiveness of stem cell-based therapy. The search included clinical trials published up until 4 January 2020, written in English, and included cohorts of women and men who had received stem cell-based therapy for SUI. The search used the following keywords in various combinations: 'stem cell therapy', 'cell-based therapy for SUI', 'regenerative medicine for SUI', and 'tissue engineering'. The success rates were assessed according to cough test, urodynamics, pad tests, and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The primary endpoint was continence rate to measure objectively the effect of the treatment., Results: We identified four clinical trials using local injections of adipose-derived stem cells (ADSCs), 11 trails with muscle-derived stem cells (MDSCs), and two trails with human umbilical cord blood stem cells (HUCBs) and total nucleated cells (TNCs). The median improvement rate of intrinsic sphincter deficiency after ADSCs, MDSCs, TNCs, HUCBs injections were 88%, 77%, 89%, 36% (improvement rate: 1-2 pads) at a mean (range) follow-up of 6 (1-72) months. The cell sources, methods of cell processing, cell number, and implantation techniques differed considerably between studies. Most of the periurethral injections were at the 3, 5, 7, and 9 o'clock positions and for submucosa were at the 4, 6, and 8 o'clock positions. No significant postoperative complications were reported., Conclusion: Despite many challenges in stem cell-based therapy for treating SUI, it appears to provide, in both male and female patients, acceptable functional results with minimal side-effects and complications. In the future, more clinical trials should be funded in order to optimise stem cell-based therapy and evaluate long-term outcomes., Abbreviations: ADSC: adipose-derived stem cell; BMSCs: bone marrow-derived mesenchymal stem cell; CLPP: cough leak-point pressure; FPL: functional profile length; HUCB: human umbilical cord blood stem cell; ICIQ-(QOL)(SF)(UI): International Consultation on Incontinence Questionnaire (Quality of life) (-Urinary incontinence Short Form) (-Urinary Incontinence); IIQ-7: Incontinence Impact Questionnaire-short form; I-QOL: Incontinence quality of life questionnaire; ISD: intrinsic urinary sphincter deficiency; MDSC: muscle-derived stem cell; MUCP: maximum urethral closure pressure; NR: not reported; Pdet-max: maximum detrusor pressure; PVR: post-void residual urine volume; Q max : maximum urinary flow; QOL: quality of life; RP: radical prostatectomy; TNC: total nucleated cell; (S)UI: (stress) urinary incontinence; UDSCs: urine-derived stem cells; UTUS: upper tract ultrasonography; VLPP: Valsalva leak-point pressure., Competing Interests: The authors declare that they have no relevant conflict of interest., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Immune checkpoint inhibitors (ICI) are an integral part of bladder cancer therapy, however, the relevance of ICI treatment for mixed and pure squamous cell carcinoma of the bladder remains poorly studied. Therefore, we analysed the expression of programmed death-ligand 1 (PD-L1) in urothelial carcinomas with squamous differentiation (UC/SCC) and pure squamous cell carcinoma (SCC) of the bladder and studied a UC/SCC patient with ICI therapy., Methods: Tissue microarrays of 45 UC/SCC and 63 SCC samples were immunohistochemically stained with four anti-PD-L1 antibodies (28-8, 22C3, SP142 and SP263). PD-L1 expression was determined for tumour cells (TP-Score), immune cells (IC-Score) and combined (CPS, combined positive score). In addition, we present clinical and histological data of an UC/SCC patient with nivolumab therapy., Results: Overall, positive PD-L1 staining ranged between 4.8 and 61.9% for IC and 0 and 51.2% for TC depending on the used antibody. There were no significant differences between UC/SCC and SCC. According to current FDA guidelines for example for first line therapy of urothelial cancer with pembrolizumab (CPS ≥ 10), a subset of SCC patients up to 20% would be eligible. Finally, our UC/SCC index patient revealed excellent therapy response regarding his lung metastasis., Conclusions: Our data reveal a PD-L1 expression in squamous differentiated carcinomas comparable with current data shown for urothelial tumours. In accordance with the encouraging clinical data of the index patient we suggest ICI treatment also for mixed and pure SCC of the urinary bladder.

Objective: To evaluate the complications and results of artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI)., Methods: A selective database search using keywords (1990-2019) was conducted to validate the effectiveness of the AUS in women. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilised. The meta-analysis included 964 women (15 studies) with persistent SUI. The Newcastle-Ottawa score was used to determine the quality of the evidence in each study. The success rate and complications associated with the AUS were analysed., Results: Meta-analysis of the published studies showed that complete continence was achieved at a mean rate of 79.6% (95% confidence interval [CI] 72.2-86.6%) and a significant improvement was achieved in 15% (95% CI 10-25%). The mean (range) follow-up was 22 (6-204) months. The mean number of patients per study was 68. The mean (range) explantation rate was 13 (0-44)%. Vaginal erosion occurred in a mean (range) of 9 (0-27)% and mechanical complications in 13 (0-47)%. Infections accounted for 7% of the complications. The total mean (range) revision rate of the implanted AUS was 15.42 (0-44)%. The mean (range) size of the cuff used was 6.7 (5-10) cm., Conclusion: Our present analysis showed that implantation of an AUS in women with severe UI is an effective treatment option after failure of first-line therapy. However, the currently available study population is too small to draw firm conclusions., Abbreviations: AMS: American Medical Systems; AUS: artificial urinary sphincter; EAU: European Association of Urology; LE: Level of Evidence; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QoL: quality of life; SHELTER: Services and Health for Elderly in Long TERm care (study); SUI: (stress) urinary incontinence., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: To evaluate predictive factors for survival outcomes after post-prostatectomy radiotherapy. Material and methods: In the years 2003-2008, 324 patients have received postoperative radiotherapy a median time of 14 months after radical prostatectomy. All patients have been treated up to 66.0-66.6 Gy in 1.8-2.0 Gy fractions. Predictive factors were analyzed at two stages, using a multivariable Cox regression analysis: (1) based on factors known before radiotherapy and (2) based on prostate-specific antigen response after radiotherapy. Results: Median follow-up after radiotherapy was 121 months. Prostate-specific antigen before radiotherapy, pN1 and Gleason score remained predictive factors for disease-free (hazard ratio, HR of 6.0, 2.3 and 2.5) and overall survival (HR of 2.8, 2.0 and 1.6) in multivariable analysis. Prostate-specific antigen levels increased despite radiotherapy in 27% of patients in the first six months. Failed response following salvage radiotherapy and prostate-specific antigen doubling time at the time of biochemical recurrence were predictive factors for disease-free (HR of 2.8 and 7.3; p  < .01) and overall survival (HR of 2.2 and 2.6; p  < .01). Conclusion: To reach the best survival outcomes following prostatectomy, salvage radiotherapy should be initiated early with low prostate-specific antigen levels, especially in patients with higher Gleason scores. Patients not responding to radiotherapy and/or patients with a short prostate-specific antigen doubling time after radiotherapy are candidates for early additional treatments.

Purpose: To analyze long-term quality-of-life (QoL) changes related to postoperative radiation therapy (RT) after radical prostatectomy., Methods and Materials: Patients who received postoperative 3-dimensional conformal RT in the years 2003 to 2008 with 1.8 to 2.0 Gy fractions up to 66.0 to 66.6 Gy (n = 181) were surveyed using the Expanded Prostate Cancer Index Composite questionnaire before the beginning of RT (A); on the last day (B); and 2 months (C), 1 to 3 years (D), 6 to 9 years (E), and 10 to 13 years (F) after RT., Results: Mean urinary bother, urinary incontinence bother, and bowel bother score changes (in relation to baseline at time A) of 13, 14, and 7 and 14, 15, and 7 were found at times E and F, respectively (P < .01 for all comparisons). Sexual function scores decreased 6 and 8 points on average (P < .01). Patient age at the time of RT had a considerable impact on urinary bother and urinary incontinence bother, with increasing differences over time when comparing patients aged <68 versus ≥68 years: 0 versus 7 and 0 versus 7 points at time D and 8 versus 23 and 6 versus 35 points at time F, respectively. Patients who did not respond to RT with a decreasing prostate-specific antigen level had greater urinary and urinary incontinence bother and bowel bother score changes >10 years after treatment (25 vs 12; P = .04, 36 vs 10; P = .03, and 20 vs 5; P = .07, respectively). A higher rectal dose was associated with greater acute and long-term bowel bother score decrease. No correlation was found between the dose to the bladder and QoL changes., Conclusions: In contrast to early evaluations in the first years, significantly decreasing QoL in the urinary, bowel, and sexual domains was found >5 years after RT. Aging is likely to be a major factor. Younger patients who responded to the treatment had the most favorable long-term QoL results. As 3-dimensional conformal RT was used in this study, intensity modulated concepts could result in improved outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pyeloplasty is one of the most common urological reconstructive interventions. Since the presentation of the first open pyeloplasty by Anderson and Hynes in 1949, the management of ureteropelvic junction obstruction has dramatically developed. The most immense progress was made in the 1990s with the introduction of laparoscopy. A multitude of new minimal surgical techniques have been introduced since then. In the last few years, the innovations were based on refinement of already-existing techniques and technology. With this aim, single-port surgery, three-dimensional vision for laparoscopy, robotic technology, and alternative techniques for creating the anastomosis-like fibrin glue have been introduced. This unsystematic review is timely, and the scientific interest is to present and discuss some of the latest advances in surgical techniques and different approaches for the intra- and post-operative management in pyeloplasty. To the best of our knowledge, this is the only review looking at the recent advances in urological surgical techniques for pyeloplasty during the last few years with a focus on new technology and surgical techniques., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

We present a case of a patient with a large, symptomatic abdominal tumour, which finally could be classified as a leiomyoma arising from the right seminal duct/seminal vesicle. In computed tomography (CT) scan, it appeared as a 7.5 × 6.5 cm solid, supravesical mass. A cystoscopy as well as bilateral retrograde studies was normal, a transrectal ultrasound-guided biopsy and an ultrasound-guided transabdominal biopsy of the mass were inconclusive. Subsequently, we performed a tumour extirpation through a lower midline laparotomy. Histological examination showed a leiomyoma arising from the right seminal duct or seminal vesicle. In this article, we discuss clinical presentation, findings on imaging and management of this rare benign tumour and review the relevant literature where only 13 similar cases could be identified., (© 2018 Blackwell Verlag GmbH.)

Bladder cancer therapy relies on aggressive treatments highlighting the need for new, targeted therapies with reduced side effects. SWI/SNF complexes are mutated in ~20% across human cancers and dependency of SWI/SNF-deficient tumors on EZH2 has been uncovered recently. To systematically dissect the frequency of genetic alterations in SWI/SNF complexes potentially contributing to their inactivation, mutations and copy number variations in 25 SWI/SNF subunit genes were analyzed making use of publicly available sequencing data for 408 muscle-invasive bladder carcinoma samples. ARID1A truncating mutations were identified as the by far most common alterations of SWI/SNF complexes in urothelial bladder cancer. As current ARID1A protein expression data in bladder cancer are inconsistent and incomplete we examined if the frequency of truncating ARID1A mutations translates into a similar frequency of cases showing ARID1A protein loss. We applied a validated ARID1A antibody conducting a comprehensive immunohistochemistry-based expression analysis in urothelial bladder cancer (n = 362) including carcinoma in situ (CIS) cases. While observing increased median ARID1A protein levels in all carcinoma subgroups compared to normal urothelial controls (n = 21), the percentage of cases showing ARID1A protein loss was positively correlated with increasing stage and grade culminating in a rate of 14.1% in muscle-invasive disease. ARID1A-depletion did neither increase EZH2 protein or trimethylated H3K27 levels in vitro nor did ARID1A expression correlate with EZH2 or H3K27me3 amounts in human bladder carcinomas. Importantly, ARID1A-deficiency was neither associated with enhanced sensitivity towards inhibition of EZH2 enzymatic activity nor depletion of EZH2 protein. In summary, ARID1A truncating mutations, potentially translating into ARID1A protein loss in a subset of high-grade bladder cancers, are the most common SWI/SNF genetic alterations in bladder cancer. Our data do not support ARID1A-deficiency as predictive biomarker for EZH2-inhibitor treatment response in bladder cancer underlining the need for future bladder cancer-specific, drug screens for successfull discovery of ARID1A-deficiency-based targeted drugs., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB., Methods: A total of 134 patients underwent intensity-modulated radiotherapy from 2007-2010. All patients received a total dose of 76 Gy with 2 Gy fractions to the prostate; 67 patients received an additional SIB of 80 Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire., Results: Baseline characteristics were similar in both groups (prostate-specific antigen 11 ng/ml vs. 8 ng/ml, p = 0.20, Gleason score <6 in 36% vs. 46%, p = 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5-6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p = 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p = 0.17)., Conclusions: The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.

Purpose: The aim of this study was to evaluate quality-of-life changes up to 10 years following three different radiotherapy concepts., Methods and Materials: In the years 2000-2003, 295 patients were treated with external beam radiotherapy (EBRT; n = 135; 70.2 Gy in 1.8 Gy fractions), low-dose-rate brachytherapy (LDR-BT with I-125; n = 94; 145 Gy), and high-dose-rate brachytherapy (HDR-BT with Ir-192; n = 66; 18 Gy in two fractions using 4-6 needles) as a boost to EBRT (50.4 Gy in 1.8 Gy fractions). Quality of life was assessed using the Expanded Prostate Cancer Index Composite at median time of 2, 6, and 10 years after treatment., Results: The urinary function score 2 years after EBRT (mean 93 points) was significantly higher in comparison to HDR-BT + EBRT (80 points, higher doses to the urethra relevant) and LDR-BT (88 points). After 10 years, only HDR-BT + EBRT (75 points) remained worse (LDR-BT 92 points; EBRT 91 points). Urinary incontinence score decreased from 83 to 76 points in the HDR-BT + EBRT group. No significant differences or changes resulted in the bowel domain. The mean sexual function score (i.e., sexuality score) was significantly higher after LDR-BT versus HDR-BT + EBRT and EBRT (30 vs. 19 and 24 points after 2 years and 25 vs. 13 and 15 points after 10 years, respectively)-a lower patient age and a lower percentage with hormonal treatment need to be considered., Conclusion: Apart from decreasing sexual function for all patients, decreasing urinary scores were found in the HDR-BT + EBRT group predominantly as a result of increasing incontinence. This study demonstrates the need for optimum BT treatment planning., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival., Methods: Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition., Results: Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01)., Conclusions: Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

Purpose: Expression profiling by DNA microarray technology permits the identification of genes underlying clinical heterogeneity of bladder cancer and which might contribute to disease progression, thereby improving assessment of treatment and prediction of patient outcome., Experimental Design: Invasive (20) and superficial (22) human bladder tumors from 34 patients with known outcome regarding disease recurrence and progression were analyzed by filter-based cDNA arrays (Atlas Human Cancer 1.2; BD Biosciences Clontech) containing 1185 genes. For 9 genes, array data were confirmed using real-time reverse transcription-PCR. Additionally, Atlas array data were validated using Affymetrix GeneChip oligonucleotide arrays with 22,283 human gene fragments and expressed sequence tags sequences in a subset of three superficial and six invasive bladder tumors., Results: A two-way clustering algorithm using different subsets of gene expression data, including a subset of 41 genes validated by the oligonucleotide array (Affymetrix), classified tumor samples according to clinical outcome as superficial, invasive, or metastasizing. Furthermore, (a) a clonal origin of superficial tumors, (b) highly similar gene expression patterns in different areas of invasive tumors, and (c) an invasive-like pattern was observed in bladder mucosas derived from patients with locally advanced disease. Several gene clusters that characterized invasive or superficial tumors were identified. In superficial bladder tumors, increased mRNA levels of genes encoding transcription factors, molecules involved in protein synthesis and metabolism, and some proteins involved into cell cycle progression and differentiation were observed, whereas transcripts for immune, extracellular matrix, adhesion, peritumoral stroma and muscle tissue components, proliferation, and cell cycle controllers were up-regulated in invasive tumors., Conclusions: Gene expression profiling of human bladder cancers provides insight into the biology of bladder cancer progression and identifies patients with distinct clinical phenotypes.

Objectives: A survey was performed to assess the current practice patterns in laparoscopy among urologists in Germany and Switzerland., Methods: Using the database directory of the German and Swiss Urological Association urological departments were identified. A detailed questionnaire was designed and sent by postal service. Responding questionnaires were analyzed., Results: The overall response rate was 64%. Fifty-four percent of respondents in Germany and 33% in Switzerland already perform laparoscopy; another 50% and 56% are planning to introduce laparoscopy. Thirty-six percent think that laparoscopy is economical and 77% await shortening of hospital stay. Major concerns are: Economical aspects, lengthy learning curve, investment, and lack of scientific data. The number of laparoscopic procedures during 12 months was registered for 19 indications. More than 40 procedures for one indication are performed by only 6% of the departments., Conclusions: The survey reveals an increasing number of departments performing laparoscopy and broad acceptance of the technology but combined with some major concerns. Currently only a minority of the departments perform more than 40 procedures for one indication suggesting that at present laparoscopy is mainly a center-based technology.

To assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6-8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR. Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR. In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.

Interleukin-6 (IL-6) is the end-product of a cytokine signaling cascade and is secreted by specialized immune cells during inflammation. It has a great influence on many functions, including differentiation, stimulation, and activation of immune cells, or other cells of neuroendocrine origin. Thus, IL-6 serves as a key messenger in its communication with the neuroendocrine system, and serves as a potent activator of the hypothalamic-pituitary-adrenal axis at all levels. Changes in the levels of expression of this cytokine and its receptor have been observed during chronic inflammatory disease, and have been associated with tumorigenesis. Therefore, we studied the effect of IL-6 on normal and adenomatous human adrenal cells in vitro. The expression of IL-6 receptor mRNA was quantified within the same tissue. IL-6 potently stimulated cortisol secretion from dispersed normal human adrenal cells. We found immunoreactivity for the IL-6 receptor on cultured cells and paraffin-embedded sections of adrenal tissues. Further, there was a more pronounced expression of IL-6 mRNA in adrenal adenomas of patients with Cushing's syndrome, compared to normal human adrenals. Despite this fact, the sensitivity of cells of adenomatous adrenal glands to IL-6 was significantly decreased relative to cells from normal controls. These results were confirmed employing the permanent adrenocortical cancer cell line model NCI-H295. We infer that the loss of responsivity of tumorous adrenal cells to IL-6, and in part corticotropin, is an important step in the process of adrenal tumorigenesis by which regulation by differentiating proteins is bypassed.

Objective(s): To compare the outcome of patients with stage D1 (TxN+M0) prostate cancer undergoing radical prostatectomy or androgen deprivation alone., Patients and Methods: Eighty-two patients treated for lymph node positive prostate cancer were retrospectively analyzed for time to progression, tumor-specific and overall survival. Furthermore, subsequent tumor and treatment related morbidity requiring intervention including frequency and duration of associated hospital stays was recorded., Results: The extent of lymph node metastasis was significantly lower in 50 patients undergoing radical prostatectomy (+/- early androgen deprivation) compared to 32 receiving androgen deprivation only. The treatment groups, however, did not differ with regard to other characteristics including age, comorbidity, stage, grade and preoperative PSA. Mean actuarial progression-free, and tumor-specific survival was significantly longer for the radical prostatectomy patients (36% and 47%, respectively at 10 years) compared to androgen deprivation (15% and 32%, respectively). The latter group required more secondary interventions resulting in more frequent and overall longer hospital stays., Conclusions: Patients undergoing radical prostatectomy for stage D1 prostate cancer possibly benefit with regard to the necessity for secondary interventions and, at least for limited (solitary) nodal disease, in terms of progression-free and tumor-specific survival. However, the latter observation may be biased by a larger extent of lymph node metastasis in the androgen deprivation group.

To evaluate the current status of laparoscopy, the "Working Group Laparoscopy" of the German Urological Association performed a questionnaire among urologists in Germany. Of 300 questionnaires 183 were returned and analyzed (61%): 54% of the departments already performed laparoscopy and another 50% are planning to introduce this technique. The major concerns are economical (70%), long learning curve (92%), investment (53%), and lack of scientific data (76%). Simple nephrectomy, cryptorchism, and varicoceles are treated by 66, 59, and 58 of the 96 departments laparoscopically (of 183 resp.). Laparoscopic surgery for radical prostatectomy and tumor nephrectomy is done by 32 and 34 of 96 departments. Only a minority of the centers performs more than 40 laparoscopies per year and indication. Compared to a survey conducted in 1995, the acceptance level of this technique has increased (100% vs 48%). Only a minority of the departments performs more than 40 laparoscopic interventions per year for one indication.

Intense efforts are being made to identify prognostic markers in superficial and muscle invasive bladder cancer in order to get more detailed information on the biological properties of urothelial cancer. Tumor associated antigens, angiogenetic factors and their inhibitors, cell adhesion molecules, cell cycle regulating genes and proteins, oncogenes and tumor suppressor genes are subjects of clinical investigations. This article provides a contemporary review of prognostic factors in bladder cancer and their possible clinical implication. A better characterization of urothelial cancer can be anticipated from new technologies allowing analysis of multiple genes or gene products in an automated one-step procedure.

Radical prostatectomy (RPE) is considered to be the "gold standard" for the treatment of localized prostate cancer regardless the fact that up to now no prospective randomized trial has compared surgery against radiotherapy, brachytherapy or a surveillance strategy. Success of RPE mainly depends on patient selection. For patients without extraprostatic tumor growth results of RPE are excellent with a rate of 80-90% of patients without biochemical recurrence during a 10 year follow up. Despite current staging modalities including digital rectal examination, preoperative prostate specific antigen and Gleason score of the biopsy between 23-53% of patients will experience PSA recurrence during a 10 year follow up. Taken together all sources of presurgical information, accuracy of predicting pathological stage it 70%. Decision towards or against RPE based on this data may be difficult in the individual patient because it is unclear from which possible chance or percentage of cure RPE is the adequate treatment. Proper selection of patients is the key to success for surgical treatment of localized prostate cancer but we need more accurate information including molecular biology technology to predict the biological behavior of the tumor.

Unlabelled: Of a total of 117 bone marrow transplant (BMT) recipients in the period from August 1988 to November 1995, 9 (7.7%) developed haemorrhagic cystitis. This condition was characterized in all nine patients by late onset (day +24 to +50 post-BMT), long duration (1 to 7 weeks), and the excretion of BK virus in the urine, as confirmed by electron microscopy, DNA hybridization and PCR analysis. Adenovirus was not involved. The serological assessment of BK virus-specific IgM and IgG pre- and post-BMT is consistent with viral reactivation in all patients, although a primary infection cannot be absolutely excluded in a single patient. A significant correlation between the use of high-dose busulphan (16 mg/kg) in the preparative regimen and development of haemorrhagic cystitis (P = 0. 0003) was evident. The severe course of the disease in two patients resulted in bladder tamponade; bleeding could not be inhibited with coagulation and laser treatment. Deterioration was prevented by bladder irrigation via a suprapubic catheter. Remission occurred spontaneously in all patients., Conclusion: BK virus induced haemorrhagic cystitis in a paediatric bone marrow transplantation recipients is characterized by late onset, long duration, viral reactivation and correlates to high-dose busulphan. Severe bleeding could not be influenced by surgical intervention.

Hemorrhagic cystitis (HC) is a major complication of bone marrow transplantation (BMT). We describe the clinical course and urological management of BK polyomavirus-associated HC in children after bone marrow transplantation. From 8/88 to 11/95, a total of 117 consecutive pediatric patients received BMT. Nine patients (7. 7%) developed HC after transplantation. HC in all 9 patients was characterized by late onset (day +24 to +50 post-BMT), long duration (1-7 weeks) and the excretion of BK polyomavirus in the urine as confirmed by electron microscopy, DNA hybridization and PCR techniques. Six children developed mild HC (grade 1-2) and were treated successfully by hyperhydration. In 3 patients, severe HC (grade 3-4) over 6 weeks required surgical interventions. In these 3 patients, cystoscopy revealed circumscript papulous tumors as the source of hematuria. Severe and persistent hematuria required blood transfusions, insertion of large suprapubic catheters and permanent bladder irrigation because of recurrent blood clot retention. Attempts to stop the hematuria in 2 of these patients by coagulation and laser vaporization (Nd:YAG) failed to stop the bleeding. Differential diagnosis of hematuria after BMT includes urinary tract infection, cyclophosphamide-induced chemical cystitis and bleeding due to BMT-induced thrombocytopenia. With the increasing number of BMTs in children, urologists may be confronted with BK polyomavirus-associated HC and must consider this in the differential diagnosis of hematuria after BMT.

A case of spontaneous, partial, unilateral thrombosis of the corpus cavernosum is described. A 35-year-old white male presented with a painful mass in the perineum without priapism. Diagnostic evaluation with sonography and magnetic resonance imaging revealed a thrombosis in the left posterior corporal body. Treatment consisted of intravenous heparin followed by prophylactic acetylsalicylic acid. The thrombosis resolved spontaneously over several months without sequelae. Conservative management of this rare disease appears to be possible and safe.

In a prospective study of 302 ureteroscopic procedures, 161 were commenced and 133 completed without the use of general or regional anaesthesia. In 15 patients ureteroscopy (URS) was performed with lignocaine jelly in the urethra only, and in 118 with additional intravenous analgesia. Alfentanil, a synthetic morphine derivative, was used for intravenous analgesia. Ureteroscopy was performed prior to extracorporeal shock wave lithotripsy in 46 patients, for stone basketing in 40, for stone fragmentation in 29, for diagnostic purposes in 14 and for cold knife ureterotomy in 4. Ureteric lesions were observed in 9 patients (6.8%) treated under intravenous sedoanalgesia. This percentage is within the range reported in other series of patients treated under general anaesthesia. The findings suggest that URS, when performed without general or regional anaesthesia, does not increase the risk of complications or compromise the results of treatment.

A new two-step technique for percutaneous nephrostomy with a newly designed nephrostomy set is described. The technique combines the advantages of the a direct introducing method (one-step nephrostomy) with an introducing trocar and the "three-step" technique with an initial puncture by a needle and insertion of a rigid guide wire. Evaluation of the different techniques in 195 patients revealed no disadvantage of the new technique compared with the three-step technique.

Routine ultrasound during pregnancy is also performed for the detection of fetal malformations. This retrospective study comprises 31 children treated for urinary tract infection within 19 months postnatally. The charts of the young patients were evaluated how often a dilatation of the upper urinary tract (more than 3 cm in diameter) was observed already during pregnancy. In 18 patients (58%) the dilatation was detected antenatally and was missed in 13 (42%). Reasons of the low sensitivity may include low technical standard of the sonographic equipment and limited skill of the investigators.