Indication for Active Surveillance in the Era of MRI-Targeted Prostate Biopsies.

INTRODUCTION: Active surveillance (AS) strategies were established to avoid overtreatment of low-risk prostate cancer (PCa) patients. Low tumor volume represents one indication criteria; however, applying this criterion after MRI-targeted prostate biopsies may lead to overestimation of tumor volume; wherefore, patients suitable for AS would be exposed to the risk of overtreatment. METHODS: This retrospective analysis included 318 patients in which PCa was detected by MRI-TRUS fusion prostate biopsy. Classic and extended indication for AS included Gleason 6 and Gleason 3 + 4 cancer, respectively. We assessed the effect of targeted biopsies and temporary rating strategies on eligibility for AS and developed new "composite" algorithms to more accurately assess eligibility for AS. RESULTS: Forty-four (13.8%) and 60 (18.9%) of the 318 patients qualified for AS according to "classic" and "extended" criteria, respectively. Application of the "composite 1" definition led to AS eligibility of 52 of 248 patients (20.97%) in the classic and of 77 of 248 patients (31.05%) in the "extended" group. CONCLUSIONS: We could demonstrate that classic algorithms led to ineligibility of patients for AS. We propose a new rating algorithm to improve tumor assessment for a more accurate indication for AS.

Enhancing disease awareness for tuberous sclerosis complex in patients with radiologic diagnosis of renal angiomyolipoma: an observational study.

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a genetic disorder, with renal manifestations like angiomyolipoma (AML) occurring in 70-80% of patients. AML usually cause more complications in TCS patients than in non-TSC patients. However, AML patients are not routinely investigated for TSC. Our aim was to retrospectively assess the correlation between radiologically diagnosed AML and TSC. METHODS: All patients were stratified into AML related vs. unrelated to TSC. Correlations were calculated to determine the association between age, AML, and TSC. RESULTS: Complete data were available for 521 patients with renal AML, in 7 of which the concurrent diagnosis of TSC was found. Younger age significantly positively correlated with the prevalence of TSC in AML patients (p <  0.01). 37 (7%) of the 521 patients were within the age-range of 18-40 years, in which TSC occurred in 6 cases, 4 (66.7%) of which presented with multiple, bilateral renal AML (p <  0.05), and 2 (33.3%) of which with a single, unilateral AML (p <  0.05). In patients with AML but without TSC, unilateral AML was found in 83.9% and bilateral AML in 16.1% (p <  0.05). Simple binary logistic regression analysis revealed bilateral AML (OR 33.0; 95% CI 3.2-344.0; p = 0.003) (but not unilateral AML (OR 0.09; 95% CI 0.01-0.88; p = 0.04)) to be a risk factor for TSC. CONCLUSIONS: The presence of bilateral AML in patients within the age-range of 18-40 years should raise suspicion for TSC as the underlying cause. Therefore, our advice is to refer patients with multiple bilateral renal AML for further investigations regarding TSC.

Antimicrobial Prophylaxis for Postoperative Urinary Tract Infections in Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: The administration of antimicrobial prophylaxis for postoperative urinary tract infections following transurethral resection of bladder tumors is controversial. We aimed to systematically review evidence on the potential effect of antimicrobial prophylaxis on postoperative urinary tract infections and asymptomatic bacteriuria. MATERIALS AND METHODS: We conducted a systematic search in Embase®, Medline® and the Cochrane Central Register of Controlled Trials. Randomized controlled trials and nonrandomized controlled trials assessing the effect of any form of antimicrobial prophylaxis in patients with transurethral resection of bladder tumors on postoperative urinary tract infections or asymptomatic bacteriuria were included. Risk of bias was assessed using RoB 2.0 or the Newcastle-Ottawa Scale. Fixed and random effects meta-analyses were conducted. As a potential basis for a scoping review, we exploratorily searched Medline for risk factors for urinary tract infections after transurethral resection of bladder tumors. The protocol was registered on PROSPERO (CRD42019131733). RESULTS: Of 986 screened publications, 7 studies with 1,725 participants were included; the reported effect sizes varied considerably. We found no significant effect of antimicrobial prophylaxis on urinary tract infections: the pooled odds ratio of the random effects model was 1.55 (95% CI 0.73-3.31). The random effects meta-analysis examining the effect of antimicrobial prophylaxis on asymptomatic bacteriuria showed an OR of 0.43 (0.18-1.04). Risk of bias was moderate. Our exploratory search identified 3 studies reporting age, preoperative pelvic radiation, preoperative hospital stay, duration of operation, tumor size, preoperative asymptomatic bacteriuria and pyuria as risk factors for urinary tract infections following transurethral resection of bladder tumors. CONCLUSIONS: We observed insufficient evidence supporting routine antimicrobial prophylaxis in patients undergoing transurethral resection of bladder tumors for the prevention of postoperative urinary tract infections; our findings may inform harmonization of international guidelines.

Single-dose versus 3-day cotrimoxazole prophylaxis in transurethral resection or greenlight laser vaporisation of the prostate: study protocol for a multicentre randomised placebo controlled non-inferiority trial (CITrUS trial).

BACKGROUND: Transurethral resection of the prostate (TURP) and Greenlight laser vaporisation (GL) of the prostate are frequently performed urological procedures. For TURP, a single-dose antimicrobial prophylaxis (AP) is recommended to reduce postoperative urinary tract infections. So far, no international recommendations for AP have been established for GL. In a survey-based study in Switzerland, Germany and Austria, urologists reported routinely extending AP primarily for 3 days after both interventions. We therefore aim to determine whether single-dose AP with cotrimoxazole is non-inferior to 3-day AP with cotrimoxazole in patients undergoing TURP or GL of the prostate. METHODS/DESIGN: We will conduct an investigator-initiated, multicentre, randomised controlled trial. We plan to assess the non-inferiority of single-dose AP compared to 3-day AP. The primary outcome is the occurrence of clinically diagnosed symptomatic urinary tract infections which are treated with antimicrobial agents within 30 days after randomisation. The vast majority of collected outcomes will be assessed from routinely collected data. The sample size was estimated to be able to show the non-inferiority of single-dose AP compared to 3-day AP with at least 80% power (1 - ß = 0.8) at a significance level of α = 5%, applying a 1:1 randomisation scheme. The non-inferiority margin was determined in order to preserve 70% of the effect of usual care on the primary outcome. For an assumed event rate of 9% in both treatment arms, this resulted in a non-inferiority margin of 4.4% (i.e. 13.4% to 9%). To prove non-inferiority, a total of 1574 patients should be recruited, in order to have 1416 evaluable patients. The study is supported by the Swiss National Science Foundation. DISCUSSION: For AP in TURP and GL, there is a large gap between usual clinical practice and evidence-based guidelines. If single-dose AP proves non-inferior to prolonged AP, our study findings may help to reduce the duration of AP in daily routine-potentially reducing the risk of emerging resistance and complications related to AP. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03633643 . Registered 16 August 2018.

Dynamics of Urinary Calprotectin after Renal Ischaemia.

BACKGROUND: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. METHODS: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. RESULTS: Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). CONCLUSION: Calprotectin and neutrophil gelatinase-associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.

Expression of histone deacetylases 1, 2 and 3 in histological subtypes of testicular germ cell tumours.

In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies.