The purpose of this study is to analyze clinical outcomes and costs of single-use flexible ureterorenoscopes in comparison with reusable flexible ureterorenoscopes in a tertiary referral center. Prospectively, 68 flexible ureterorenoscopies utilizing reusable (Flex-X2S, Flex-X, Karl Storz) and 68 applying single-use flexible ureterorenoscopes (LithoVue, Boston Scientific) were collected. Clinical outcome parameters such as overall success rate, complication rates according to Clavien-Dindo, operation time and radiation exposure time were measured. Cost analysis was based on purchase costs and recurrent costs for repair and reprocessing divided by number of procedures. In each group 68 procedures were available for evaluation. In 91% of reusable and 88% of single-use ureterorenoscopies stone disease was treated with a mean stone burden of 101 ± 226 and 90 ± 244 mm and lower pole involvement in 47 and 41%, respectively (p > 0.05). Comparing clinical outcomes of reusable vs. single-use instruments revealed no significant difference for overall success rates (81 vs. 87%), stone-free rates (82 vs. 85%), operation time (76.2 ± 46.8 vs. 76.8 ± 40.2 min), radiation exposure time (3.83 ± 3.15 vs. 3.93 ± 4.43 min) and complication rates (7 vs. 17%) (p > 0.05). A wide range of repair and purchase costs resulted in total to $1212-$1743 per procedure for reusable ureterorenoscopy whereas price of single-use ureterorenoscopy was $1300-$3180 per procedure. The current work provided evidence for equal clinical effectiveness of reusable and single-use flexible ureterorenoscopes. Partially overlapping ranges of costs for single-use and reusable scopes stress the importance to precisely know the expenses and caseload when negotiating purchase prices, repair prices and warranty conditions.

This study shows the feasibility of a randomized pilot study assessing ERAS compared to SP post RC. ERAS protocol provided evidence of significant benefits over SP with similar complication rates. This study suggests the need for a clinical trial of assessing ERAS protocols after RC.

Of 4 nephrometry scores the R.E.N.A.L. score correlated best with MIC achievement and quantitative perioperative outcomes of nephron sparing surgery.

The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo. Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.

Objectives While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. Methods In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. Results 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21-24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). Conclusion The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

The acquisition of an invasive phenotype by epithelial cells occurs through a loss of cellular adhesion and polarity, heralding a multistep process that leads to metastatic dissemination. Since its characterization in 1995, epithelial-mesenchymal transition (EMT) has been closely linked to the metastatic process. As a defining aspect of EMT, loss of cell adhesion through downregulation of E-cadherin is carried out by several transcriptional repressors; key among them the SNAI family of transcription factors. Here we identify for the first time that Lyn kinase functions as a key modulator of SNAI family protein localization and stability through control of the Vav-Rac1-PAK1 (Vav-Rac1-p21-activated kinase) pathway. Accordingly, targeting Lyn in vitro reduces EMT and in vivo reduces metastasis of primary tumors. We also demonstrate the clinical relevance of targeting Lyn as a key player controlling EMT; patient samples across many cancers revealed a strong negative correlation between Lyn and E-cadherin, and high Lyn expression in metastatic tumors as well as metastasis-prone primary tumors. This work reveals a novel pancancer mechanism of Lyn-dependent control of EMT and further underscores the role of this kinase in tumor progression.

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