Comparative retrospective assessment of the effectiveness and risk factors of fluoroquinolones, cephalosporines and selective antibiotic prophylaxis for transrectal prostate biopsy.

INTRODUCTION: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. METHODS: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as: fever >38.0°C, in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µl and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, -duration and comorbidities were also assessed. Chi-Square and Fishers exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. RESULTS: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6%, 13.3%, 25%, p<0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p<0.05). Arterial hypertension showed increased association with fever (OR 6.002 [1.178;30.597] p=0.031) and cUTI (OR 6.006 [1.207;29.891] p=0.029). CONCLUSION: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Discrepancy between German S3 Guideline Recommendations and Daily Urologic Practice in the Management of Nonmuscle Invasive Bladder Cancer: Results of a Binational Survey.

INTRODUCTION: Guideline recommendations are meant to help minimize morbidity and to improve the care of nonmuscle invasive bladder cancer (NMIBC) patients but studies have suggested an underuse of guideline-recommended care. The aim of this study was to evaluate the level of adherence of German and Austrian urologists to German guideline recommendations. METHODS: A survey of 27 items evaluating diagnostic and therapeutic recommendations (15 cases of strong consensus and 6 cases of consensus) for NMIBC was administered among 14 urologic training courses. Survey construction and realization followed the checklist for reporting results of internet e-surveys and was approved by an internal review board. RESULTS: Between January 2018 and June 2019, a total of 307 urologists responded to the questionnaire, with a mean response rate of 71%. The data showed a weak role of urine cytology (54%) for initial diagnostics although it is strongly recommended by the guideline. The most frequently used supporting diagnostic tool during transurethral resection of the bladder was hexaminolevulinate (95%). Contrary to the guideline recommendation, 38% of the participants performed a second resection in the case of pTa low-grade NMIBC. Correct monitoring of Bacille Calmette-Guérin (BCG) response with cystoscopy and cytology was performed by only 34% of the urologists. CONCLUSIONS: We found a discrepancy between certain guideline recommendations and daily routine practice concerning the use of urine cytology for initial diagnostics, instillation therapy with a low monitoring rate of BCG response, and follow-up care with unnecessary second resection after pTa low-grade NMIBC in particular. Our survey showed a moderate overall adherence rate of 73%. These results demonstrate the need for sharpening awareness of German guideline recommendations by promoting more intense education of urologists to optimize NMIBC care thus decreasing morbidity and mortality rates.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

A comparison of patient and parental experiences and diagnostic quality of suprapubic versus transurethral voiding cystourethrogram in children.

INTRODUCTION: Voiding cystourethrogram (VCUG) used in the radiologic evaluation of the upper and lower urinary tract can be performed by suprapubic puncture (SP) or by transurethral catheterization (TC). Data on which instillation technique is superior are scarce. VCUG tends to be a distressing procedure for both parents and children. METHODS: We evaluated the experience of VCUG analyzing 417 families with focus on contrast medium instillation in groups of single and repeated VCUGs and assessed quality and complication rate. The median age of children who had undergone VCUG was 38.6 months (0 - 159 months). Satisfaction with informed consent (IC), degree of fear and pain in parents and children prior and during VCUG were recorded. VCUG was compared to blood withdrawal and vaccination. RESULTS: Satisfaction with IC was higher for repeated VCUG (p= 0.024) which resulted in a lower degree of fear in parents and children. The fear of children during VCUG was lower when SP was performed rather than TC. This was in contrast to parental fear of SP (all p< 0.05). In repeated VCUGs, children who underwent SP were less afraid. Better diagnostic quality was more commonly reported with SP, yet the complication rate was higher (p=0.035). CONCLUSIONS: Our study highlights the importance of IC as a pivotal necessity before VCUG is conducted. SP might be beneficial over TC in terms of fear and distress in the case of repeated VCUGs. Diagnostic quality is comparable, both methods are safe and complications are low.

Predictors of Unfavorable Pathology in Patients with Incidental (pT1a-T1b) Prostate Cancer.

BACKGROUND: Incidental prostate cancer (IPCa) is encountered in 10% of surgical procedures for benign prostatic obstruction (BPO). Identification of patients with underlying detrimental prostate cancer is paramount for tailored treatment decision-making, but guideline recommendations for this setting are lacking. OBJECTIVE: To highlight clinical and histological characteristics related to BPO surgery that may predict IPCa with unfavorable pathology. DESIGN, SETTING, AND PARTICIPANTS: We included men with IPCa who underwent radical prostatectomy (RP) in the short term after IPCa diagnosis. Two cohorts were built according to final pathology for the RP specimen: unfavorable pathology (International Society of Urological Pathology [ISUP] grade group [GG] ≥3 and/or ≥pT3a and/or pN1) versus favorable pathology. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multivariate regression analysis for the endpoint, which was unfavorable pathology for the RP specimen. Using the model estimates for prostate-specific antigen (PSA), ISUP GG, age, and prostate volume, we established a model for estimating the risk of unfavorable histopathology. RESULTS AND LIMITATIONS: Overall, 112 patients were included in the final assessment. On multivariate analysis, PSA (odds ratio [OR] 1.083, 95% confidence interval [CI] 1.003-1.170; p = 0.042), ISUP GG for the specimen from BPO surgery (OR 3.090; 95% CI 1.129-8.457; p = 0.028), and age (OR 1.121, 95% CI 1.026-1.225; p = 0.012) were independent predictors for unfavorable histopathology. On receiver operating characteristic analysis, the area under the curve was 0.751. A novel calculator was developed to predict adverse pathology for men with IPCa. The study is limited by its retrospective design. CONCLUSIONS: For men with IPCa, PSA before surgery for BPO, ISUP GG, and age are independent predictors of unfavorable disease. Our results might improve preoperative risk assessment for patient counseling. PATIENT SUMMARY: We developed a novel calculator to estimate the risk of underlying detrimental disease in men diagnosed with prostate cancer at surgery for benign prostatic obstruction.

The timing of initial imaging in testicular cancer: impact on radiological findings and clinical decision making.

BACKGROUND: In testicular cancer determination of clinical stage and recommendation of therapeutic strategy after inguinal orchiectomy are based on primary imaging by CT-scan of the chest and CT- or MRI-abdomen. It has not been investigated so far whether the imaging should be performed before or after primary testicular surgery. Staging before surgery means exposing all patients to CT radiation irrespective of ensured histologic malignancy while postoperative staging could pose a risk in biased clinical decision making by increased presence of unspecific lymph node enlargement caused by postsurgical effects. Therefore, we aimed to investigate the association between the timing of initial staging and occurrence of unspecific lymph node enlargement and adjuvant therapies after inguinal orchiectomy. METHODS: We retrospectively evaluated clinical and radiological data from 236 patients who had undergone inguinal orchiectomy for testicular cancer at our department. Statistical analysis was performed to determine whether the occurrence of unspecific lymph node enlargement or the rate of adjuvant therapies were influenced by timing of initial staging (preoperative vs. postoperative). RESULTS: The postoperative imaging cohort showed significant more inguinal, pelvic and retroperitoneal unspecific lymph node enlargement than the preoperative imaging cohort. Simultaneous occurrence of inguinal or pelvic lymph node enlargement together with retroperitoneal enlargements could only be found in the postoperative imaging cohort. No difference regarding adjuvant therapies could be found. CONCLUSIONS: Timing of imaging affects the detection rate of unspecific lymph node enlargements but does not show a significant effect on the rate of adjuvant therapies.

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer.

BACKGROUND: Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone-sensitive prostate cancer (mHSPC). Real-world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. METHODS: In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression-free survival 1 (PFS1), and progression-free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. The Cox-proportional hazards model was used for univariate and multivariate regression analyses. RESULTS: Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log-rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183-0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128-0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups. CONCLUSIONS: AA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression-free end-points.

Targeting the glucocorticoid receptor signature gene Mono Amine Oxidase-A enhances the efficacy of chemo- and anti-androgen therapy in advanced prostate cancer.

Despite increasing options for treatment of castration-resistant prostate cancer, development of drug resistance is inevitable. The glucocorticoid receptor (GR) is a prime suspect for acquired therapy resistance, as prostate cancer (PCa) cells are able to increase GR signaling during anti-androgen therapy and thereby circumvent androgen receptor (AR)-blockade and cell death. As standard AR-directed therapies fail to block the GR and GR inhibitors might result in intolerable side effects, the identification of GR signature genes, which are better suited for a targeted approach, is of clinical importance. Therefore, the specific epithelial and stromal GR signature was determined in cancer-associated fibroblasts as well as in abiraterone and enzalutamide-resistant cells after glucocorticoid (GC) treatment. Microarray and ChIP analysis identified MAO-A as a directly up-regulated mutual epithelial and stromal GR target, which is induced after GC treatment and during PCa progression. Elevated MAO-A levels were confirmed in in vitro cell models, in primary tissue cultures after GC treatment, and in patients after neoadjuvant chemotherapy with GCs. MAO-A expression correlates with GR/AR activity as well as with a reduced progression-free survival. Pharmacological MAO-A inhibition combined with 2nd generation AR signaling inhibitors or chemotherapeutics results in impaired growth of androgen-dependent, androgen-independent, and long-term anti-androgen-treated cells. In summary, these findings demonstrate that targeting MAO-A represents an innovative therapeutic strategy to synergistically block GR and AR dependent PCa cell growth and thereby overcome therapy resistance.

Immunotherapy in prostate cancer: new horizon of hurdles and hopes.

PURPOSE: Prostate cancer (PCa) is the most common malignancy in men and the cause for the second most common cancer-related death in the western world. Despite ongoing development of novel approaches such as second generation androgen receptor targeted therapies, metastatic disease is still fatal. In PCa, immunotherapy (IT) has not reached a therapeutic breakthrough as compared to several other solid tumors yet. We aimed at highlighting the underlying cellular mechanisms crucial for IT in PCa and giving an update of the most essential past and ongoing clinical trials in the field. METHODS: We searched for relevant publications on molecular and cellular mechanisms involved in the PCa tumor microenvironment and response to IT as well as completed and ongoing IT studies and screened appropriate abstracts of international congresses. RESULTS: Tumor progression and patient outcomes depend on complex cellular and molecular interactions of the tumor with the host immune system, driven rather dormant in case of PCa. Sipuleucel-T and pembrolizumab are the only registered immune-oncology drugs to treat this malignancy. A plethora of studies assess combination of immunotherapy with other agents or treatment modalities like radiation therapy which might increase its antineoplastic activity. No robust and clinically relevant prognostic or predictive biomarkers have been established yet. CONCLUSION: Despite immunosuppressive functional status of PCa microenvironment, current evidence, based on cellular and molecular conditions, encourages further research in this field.

Telemedicine Online Visits in Urology During the COVID-19 Pandemic-Potential, Risk Factors, and Patients' Perspective.

The current coronavirus disease 2019 (COVID-19) pandemic has placed considerable strain on hospital resources. We explored whether telemedicine (defined as a videoconference) might help. We undertook prospective structured phone interviews of urological patients (n = 399). We evaluated their suitability for telemedicine (judged by a panel of four physicians) and their risks from COVID-19 (10 factors for a poor outcome), and collected willingness for telemedicine and demographic data. Risk factors for an adverse outcome from COVID-19 infection were common (94.5% had one or more) and most patients (63.2%) were judged suitable for telemedicine. When asked, 84.7% of patients wished for a telemedical rather than a face-to-face consultation. Those favouring telemedicine were younger (68 [58-75] vs 76 [70-79.2] yr, p < 0.001). There was no difference in preference with oncological (mean 86%) or benign diagnoses (mean 85%), or with COVID-19 risks factors. In subgroup analysis, men with prostate cancer preferred telemedicine (odds ratio: 2.93 [1.07-8.03], p = 0.037). We concluded that many urological patients have risk factors for a poor outcome from COVID-19 and most preferred telemedicine consultations at this time. This appears to be a solution to offer contact-free continuity of care. PATIENT SUMMARY: Risk factors for a severe course of coronavirus disease 2019 are common (94.5%) in urology patients. Most patients wished for a telemedical consultation (84.7%). This appears to be a solution to offer contact-free continuity of care.

Treatment of non-metastatic castration resistant prostate cancer in 2020: What is the best?

Lately the development of 3 novel second-generation androgen receptor antagonists (enzalutamide, apalutamide, and darolutamide) chanced the treatment landscape of nonmetastatic castration-resistant prostate cancer. After proofing their clinical efficacy in large phase III registration trials with good compatibilities and tolerable side effects currently all 3 substances are Food and Drug Administration-approved in nonmetastatic castration-resistant prostate cancer. The present short review article provides an overview about these new treatment options and discusses their use in daily routine focusing on patient selection as well as on the impact of novel sensitive imaging modalities like prostate-specific membrane antigen-positron-emission tomography for detection of this stage of disease.

Immune check point inhibitors for metastatic urothelial carcinoma: current evidence-based approach for urology daily practice.

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

Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical factors for successful treatment response and improvement in overall survival.

PURPOSE: The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC). METHODS: An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival. RESULTS: Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64-104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5-16 m) and 20 m (IQR 16-26 m), respectively. Partial PSA-response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third-sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC > 47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p = 0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment-free interval > 3 m (Hazard Ratio 3.49; p = 0.014) were the only independent predictive factors under taxane treatment for overall survival. CONCLUSION: Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval > 3 m benefit most from docetaxel re-exposure.

Nationwide analysis on the impact of socioeconomic land use factors and incidence of urothelial carcinoma.

BACKGROUND: Incidence rates for urothelial carcinoma (UC) have been reported to differ between countries within the European Union (EU). Besides occupational exposure to chemicals, other substances such as tobacco and nitrite in groundwater have been identified as risk factors for UC. We investigated if regional differences in UC incidence rates are associated with agricultural, industrial and residential land use. METHODS: Newly diagnosed cases of UC between 2003 and 2010 were included. Information within 364 administrative districts of Germany from 2004 for land use factors were obtained and calculated as a proportion of the total area of the respective administrative district and as a smoothed proportion. Furthermore, information on smoking habits was included in our analysis. Kulldorff spatial clustering was used to detect different clusters. A negative binomial model was used to test the spatial association between UC incidence as a ratio of observed versus expected incidence rates, land use and smoking habits. RESULTS: We identified 437,847,834 person years with 171,086 cases of UC. Cluster analysis revealed areas with higher incidence of UC than others (p=0.0002). Multivariate analysis including significant pairwise interactions showed that the environmental factors were independently associated with UC (p<0.001). The RR was 1.066 (95% CI 1.052-1.080), 1.066 (95% CI 1.042-1.089) and 1.067 (95% CI 1.045-1.093) for agricultural, industrial and residential areas, respectively, and 0.996 (95% CI 0.869-0.999) for the proportion of never smokers. CONCLUSION: This study displays regional differences in incidence of UC in Germany. Additionally, results suggest that socioeconomic factors based on agricultural, industrial and residential land use may be associated with UC incidence rates.

Resistance to nanoparticle albumin-bound paclitaxel is mediated by ABCB1 in urothelial cancer cells.

Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab-paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC-SUP, as well as sub-lines with acquired resistance against gemcitabine (T24rGEMCI20 and TCC-SUPrGEMCI20) and vinblastine (T24rVBL20 and TCC-SUPrVBL20) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1-inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab-paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.

What should be the patient's preference regarding the choice of hospital in the case of radical cystectomy? Evaluation of early complications after open radical cystectomy in a medium and high volume setting in one hospital.

PURPOSE: This study compares early complications after cystectomy and urinary diversion (UD) stratified by the surgical focus and case load of two different department chairpersons in a single institution in two time periods. Creating clear data about complications that can affect the quality of life is an important tool for patients to decide whether and where to perform this extensive surgery. HYPOTHESIS: A team of surgeons with a clear focus on pelvic surgery leads to lower complication rates in radical cystectomy. MATERIALS AND METHODS: Radical cystectomy was performed in two separate time periods under the patronage of two different chairmen in the same university hospital. The patient data were analyzed retrospectively and the complications 30 days after surgery were assessed using the Clavien-Dindo classification. RESULTS: Statistical analysis showed a significant difference in the severity of complications between the two time periods, A and B, in total (P<0.001). When placing patients into subgroups, significantly more complications in period A were also seen concerning sex (male, P<0.001; female, P=0.003), age (<70 years, P<0.001; >70 years, P≤50.001) tumor grade (low grade, P<0.001; high grade, P≤0.001), and UD (ileal conduit, P<0.001; neobladder, P<0.001). In a multivariable analysis, age (P=0.031) and type of UD (P=0.028) were determined as independent predictors for complications in period A. When joining the two periods together, the type of UD (P=0.0417), age (P=0.041), and the time periods (A/B) (P<0.001) show a significant association with the presence of complications. CONCLUSION: This study compares for the first time surgical complications in two time periods with different case load and surgical focus in one department. Categorization shows that patients should prefer radical cystectomy in centers of excellence or a high-volume hospital in order to keep complications at the lowest possible level and thus have the highest benefit for oncologic outcome and quality of life.

Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts.

BACKGROUND: Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112rGEMCI20 in vitro and in vivo. METHODS: RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112rGEMCI20) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. RESULTS: Dasatinib exerted similar effects on Src signaling in RT112 and RT112rGEMCI20 cells but RT112rGEMCI20 cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC50) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC50 of dasatinib in RT112rGEMCI20 cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112rGEMCI20 tumors. CONCLUSION: Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.

Qualitative Twitter analysis of participants, tweet strategies, and tweet content at a major urologic conference.

INTRODUCTION: The microblogging social media platform Twitter is increasingly being adopted in the urologic field. We aimed to analyze participants, tweet strategies, and tweet content of the Twitter discussion at a urologic conference. METHODS: A comprehensive analysis of the Twitter activity at the European Association of Urology Congress 2013 (#eau2013) was performed, including characteristics of user profiles, engagement and popularity measurements, characteristics and timing of tweets, and content analysis. RESULTS: Of 218 Twitter contributors, doctors (45%) were the most frequent, ahead of associations (15%), companies (10%), and journals (3%). However, journals had the highest tweet/participant rate (22 tweets/participant), profile activity (median: 1177, total tweets, 1805 followers, 979 following), and profile popularity (follower/following ratio: 2.1; retweet rank percentile: 96%). Links in a profile were associated with higher engagement (p<0.0001) and popularity (p<0.0001). Of 1572 tweets, 57% were original tweets, 71% contained mentions, 20% contained links, and 25% included pictures. The majority of tweets (88%) were during conference hours, with an average of 24.7 tweets/hour and a peak activity of 71 tweets/hour. Overall, 59% of tweets were informative, led by the topics uro-oncology (21%), urologic research (21%), and urotechnology (12%). Limitations include the analysis of a single conference analysis, assessment of global profile and not domain-specific activity, and the rapid evolution in Twitter-using habits. CONCLUSION: Results of this single conference qualitative analysis are promising for an enrichment of the scientific discussions at urologic conferences through the use of Twitter.