ΔNp63 transcript loss in bladder cancer constitutes an independent molecular predictor of TaT1 patients post-treatment relapse and progression

Purpose: Bladder cancer represents a major cause of malignancy-related morbidity and the most expensive per-patient-to-treat cancer, due to the lifelong surveillance of the patients. Accurate disease prognosis is essential in establishing personalized treatment decisions; yet optimum tools for precise risk stratification remain a competing task. In the present study, we have performed the complete evaluation of TP63 clinical significance in improving disease prognosis. Methods: The levels of ΔNp63 and TAp63 transcripts of TP63 were quantified in 342 bladder tissue specimens of our screening cohort (n = 182). Hedegaard et al. (Cancer Cell 30:27–42. doi:10.1016/j.ccell.2016.05.004, 2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts for NMIBC and MIBC, respectively. Survival analysis was performed using recurrence and progression for NMIBC or mortality for MIBC as endpoint events. Bootstrap analysis was performed for internal validation, while decision curve analysis was used for the evaluation of the clinical net benefit on disease prognosis. Results: ΔNp63 was significantly expressed in bladder tissues, and was found to be over-expressed in bladder tumors. Interestingly, reduced ΔNp63 levels were correlated with muscle-invasive disease, high-grade tumors and high-EORTC-risk NMIBC patients. Moreover, ΔNp63 loss was independently associated with higher risk for NMIBC relapse (HR = 2.730; p = 0.007) and progression (HR = 7.757; p = 0.016). Hedegaard et al. and TCGA validation cohorts confirmed our findings. Finally, multivariate models combining ΔΝp63 loss with established prognostic markers led to a superior clinical benefit for NMIBC prognosis and risk stratification. Conclusions: ΔΝp63 loss is associated with adverse outcome of NMIBC resulting in superior prediction of NMIBC early relapse and progression. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Pressure matters: intrarenal pressures during normal and pathological conditions, and impact of increased values to renal physiology

PurposeTo perform a review on the latest evidence related to normal and pathological intrarenal pressures (IRPs), complications of incremented values, and IRP ranges during endourology.MethodsA literature search was performed using PubMed, restricted to original English-written articles, including animal, artificial model, and human studies. Different keywords were: percutaneous nephrolithotomy, PCNL, ureteroscopy, URS, RIRS, irrigation flow, irrigation pressure, intrarenal pressure, intrapelvic pressure and renal pelvic pressure.ResultsNormal IRPs range from zero to a few cm H2O. Pyelovenous backflow may occur at pressure range of 13.6-27.2cm H2O. During upper tract endourology, complications such as pyelorenal backflow, sepsis, and renal damage are directly related to increased IRPs. Duration of increased IRPs and concomitant obstruction are independent predictors of complication development.ConclusionsIRP increase remains a neglected predictor of upper tract endourology complications and its intraoperative monitoring should be taken into consideration. Further research is necessary, to quantify pressures generated during upper tract endourology, and introduce means of controlling them

Predictors and Strategies to Avoid Mortality Following Ureteroscopy for Stone Disease: A Systematic Review from European Association of Urologists Sections of Urolithiasis (EULIS) and Uro-technology (ESUT)

Ureteroscopy is a common endourological procedure with a low risk of mortality, mostly linked to sepsis. Patients must therefore have robust preoperative assessment, intraoperative techniques, and postoperative monitoring for early detection of complications with interdisciplinary management of complex cases. © 2021 European Association of Urology Context: While kidney stone disease is common and ureteroscopy (URS) is perceived as minimally invasive, there is mortality associated with treatment. Objective: The aim of this review was to ascertain the number of mortalities from URS for stone disease over the past three decades, identify relevant patient risk factors and predictors of mortality, and summarise the key recommendations so that similar instances can be avoided, and lessons can be learnt. Evidence acquisition: A systematic literature search was conducted following Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology for English-language article reporting on data from 1990 to December 2020. Data collated from each study included patient and stone characteristics, number of mortalities, and cause of death. Evidence synthesis: Fifteen studies met our inclusion criteria and revealed a total of 72 mortalities from ten countries. The age range of reported patients varied from 21 to 89 yr, with over 60% being above 65 yr of age and 97% with some comorbidity. Based on available data, death reports in females were three times more than those in males. The stone size ranged from 10 to 38 mm. Treatment of larger stones corresponded to a longer operative time, with procedural duration varying from 30 to 120 min. Of the reported causes of mortality in 42 patients, the aetiology was sepsis in over half of the patients, with other causes being cardiac-related, respiratory-related, multiorgan failure, and haemorrhagic complications. Conclusions: Although the reported URS mortality rate seems to be low, there has been a rise in deaths over the past decade. Efforts must be made to have preoperative urine culture, and reduce operative time and stage procedures in patients with a large stone burden. Care must be taken in patients with robust preoperative assessment, intraoperative techniques, and postoperative monitoring for early detection of complications with interdisciplinary management of complex cases. Patient summary: We reviewed the risk factors associated with postureteroscopy mortality and ways to minimise this. Evidence shows that although reported mortality remains low, there seems to be an increase in morality in the past decade and urologists must remain vigilant of this. © 2021 European Association of Urolog