The latest medical research on Urology

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Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.

Prostate

The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay.

Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high).

The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24).

Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.

Cost Effectiveness of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: Results of the ROSETTA Randomized Trial.

J Urol

Sacral neuromodulation and intradetrusor injection of onabotulinumtoxinA are therapies for refractory urgency-urinary incontinence. Sacral neuromodulation involves surgical implant of a device that can last 4-6 years, while onabotulinumtoxinA involves serial office injections. Objective was to assess cost-effectiveness of 2-stage implantation sacral neuromodulation versus 200 units onabotulinumtoxinA for the treatment of urgency-urinary incontinence.

Prospective economic evaluation concurrent with Refractory Overactive Bladder: Sacral NEuromodulation v. BoTulinum Toxin Assessment (ROSETTA) randomized trial of 386 women with ≥ 6 urgency-urinary-incontinence episodes in 3-day diary. Analysis from healthcare system perspective, with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs in 2018 U.S. dollars. Effectiveness measured in quality-adjusted life-years (QALYs) and reductions in urgency-urinary-incontinence episodes/day. Generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves.

Two-year costs were higher for sacral neuromodulation versus onabotulinumtoxinA ($35,680 [95%CI $33,920-$37,440] versus $7,460 [95%CI $5,780-$9,150], p<0.01), persisting through 5 years ($36,550 [95%CI $34,787-$38,309] versus $12,020 [95%CI $10,330-$13,700], p<0.01). At 2 years, there were no differences in mean reduction in urgency-urinary-incontinence episodes/day (-3.00 [95%CI -3.38 - -2.62] versus -3.12 [95%CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95%CI 1.34-1.44] versus 1.41 [95%CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost effective relative to onabotulinumtoxinA is less than 0.025 for all willingness-to-pay values below $580,000/QALY at 2 years and $204,000/QALY at 5 years.

Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency-urinary incontinence compared with 200 units onabotulinumtoxinA.

Urinary Stone Disease in Pregnancy: A Claims-Based Analysis of 1.4 Million Patients.

J Urol

Urinary stone disease during pregnancy is poorly understood but is thought to be associated with increased maternal and fetal morbidity. We sought to determine the prevalence of urinary stone disease in pregnancy and whether urinary stone disease during pregnancy is associated with adverse pregnancy outcomes.

We identified all pregnant women from 2003 through 2017 in the Optum national insurance claims database. We used diagnosis claims to identify urinary stone disease and assess medical comorbidity. We established the prevalence of urinary stone disease during pregnancy, stratified by week of pregnancy. We further evaluated associations among urinary stone disease and maternal complications and pregnancy outcomes in both univariable and multivariable analyses.

Urinary stone disease affects 8/1000 pregnancies and is more common in white women and women with more comorbid conditions. In fully adjusted models, pregnancies complicated by urinary stone disease had higher rates of adverse fetal outcomes, including prematurity and spontaneous abortions. This analysis is limited by its retrospective administrative claims design.

The rate of urinary stone disease during pregnancy is higher than previously reported. Urinary stone disease is associated with adverse pregnancy outcomes.

A Randomized, Double-Blinded, Control Trial Shows that Onabotulinum Toxin a (Botox®) Nerve Blocks Do Not Provide Improved Pain Control for Men with Chronic Scrotal Pain.

J Urol

The use of Onabotulinum Toxin A (BTX) to chemically denervate the testis has been studied as a minimally invasive therapy to treat chronic scrotal pain (CSP). To date no randomized control trials on BTX use for CSP management have been reported.

In this double-blinded randomized control trial, men with CSP who had at least temporary pain relief following a cord block with local anaesthetic (LA) were randomly assigned to blocks using LA alone vs. LA plus 200IU BTX. Standardized assessments of pain levels (visual analog scores: VAS), disease impact, quality of life and mood was performed at 1, 2, 3, 4, 12 and 18 weeks post-injection. The primary outcome was the change in VAS at one month. After completion of the study, men in the control group were given the option to receive BTX as part of an open-label trial.

Of 64 men (mean age 45.9±11 and duration of pain 5.7 ±5.7 years), 32 received LA/BTX and 32 LA alone. There was no statistically significant difference in any measured outcome comparing BTX to controls. 9/13 (69.2%) men in the open label trial demonstrated an improvement of their VAS score (mean group VAS score 6.1 +/- 1.66 to 4.5 +/- 2.36, p=0.022, student's t-test) with 6/9 (66.7%) having persistent pain reduction at 3 months.

This randomized, double-blinded, controlled trial does not show superiority of BTX/LA over LA alone for pain control for men with CSP. Interestingly, there was significant pain improvement noted in our open label BTX trial, suggesting a potential placebo effect.

Sperm Genomic Integrity by TUNEL Varies Throughout the Male Genital Tract.

J Urol

To assess sperm chromatin fragmentation (SCF) at different levels of the male genital tract.

Ejaculated specimens from consenting male partners were screened for SCF by terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL). Men with ICSI failure and high ejaculated SCF underwent surgery to retrieve spermatozoa from different levels of the male genital tract, which were then reassessed for SCF. Approximately ≥500 spermatozoa were assessed per patient, with a 15% threshold. ICSI results from cycles using spermatozoa from different levels of the male genital tract were compared.

Topographical assessment of the male genital tract showed a 20.4±10% SCF in the vas deferens, 15.8±8% in the epididymis, and 11.4±6% in the testis; all lower than the ejaculated controls (32.9±20%; P<0.05). Couples (n=25) who underwent ICSI with surgically retrieved (SR) spermatozoa had lower SCF (P<0.001) and higher implantation, clinical pregnancy, and delivery rates (P<0.01). Couples (n=45) with history of ICSI failure elsewhere with ejaculate were treated solely with SR spermatozoa at our center. Compared to historical cycles, SR spermatozoa had a lower fertilization rate (65%, P<0.05) but enhanced implantation (19.1%), clinical pregnancy (40.0%), and delivery rates (34.3%; P<0.01).

For the first time, we demonstrate that SCF increases progressively from the testicle, to the epididymis, vas deferens, and is highest in the ejaculate. Men with high ejaculated SCF can benefit from using SR sperm for IVF/ICSI.

Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment.

BJU International

Whilst whole gland radical treatment is highly effective for prostate cancer control, it confers significant impact on quality of life (QOL) and is unnecessary 'over-treatment' in many men with screening detected prostate cancer. Improvements in prostate biopsy and imaging have led to the increased interest in partial gland ablation to reduce treatment-related morbidity. Several energies for focal ablation have been trialled. Irreversible electroporation (IRE) is a novel technology which ablates tissue by delivering direct current between electrodes. This narrative review aims to document the history of electroporation including its scientific basis, early data from pre-clinical animal studies and contemporary clinical outcomes from the use of IRE in prostate cancer.

A literature search using MEDLINE, Embase, PubMed and Google Scholar was undertaken to identify historical perspectives and current clinical data relating to IRE for prostate cancer.

The history of electroporation and its implementation as a prostate cancer treatment was following the basic scientific principles, in-vitro data then animal studies and now short- to medium-term clinical cohorts in humans. The results of IRE on more than 283 patients have been published in several papers, with preserved rates of (pad-free) continence in 91-100% of men and preserved erectile function in 79-100% of men. In-field recurrence rates range from 0% to 33%. The current state of evidence for IRE in treatment of primary and salvage prostate cancer is considered IDEAL stage 2B.

IRE is a new focal ablative technology for the treatment of localised prostate cancer in carefully selected men. Published cohorts reported encouraging short-term oncological and functional outcomes, however longer-term data is needed to validate this treatment before it can be recommended for widespread clinical use.

The added value of diffusion-weighted images and dynamic contrast-enhancement in multi-parametric MRI for the detection of clinically significant prostate cancer in the PICTURE trial.

BJU International

To determine the additional diagnostic value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) imaging in men requiring a repeat biopsy within the PICTURE study.

PICTURE was a paired-cohort confirmatory study in which 249 men who required further risk stratification following a previous non-MRI guided TRUS biopsy underwent a 3-Tesla mpMRI consisting of T2W, DWI and DCE followed by transperineal template prostate mapping (TPM) biopsy. Each mpMRI was reported using a LIKERT score in a sequential blinded manner to generate scores for T2W, T2W+DWI and T2W+DWI+DCE. Area under the receiver operating characteristic (AUROC) fanalysis was performed to compare the diagnostic accuracy of each combination. The threshold for a positive mpMRI was set as a LIKERT score >/=3. Clinically significant prostate cancer was analysed across a range of definitions including UCL/Ahmed Definition 1 (primary definition), UCL/Ahmed Definition 2, any Gleason >/=3+4 and any Gleason >/=4+3.

Of 249, sequential MRI reporting was available for 246. There was a higher rate of equivocal lesions (44.6%) using T2W alone compared to the addition of DWI (23.9%) and DCE (19.8%). Using the primary definition of clinically significant disease, there was no significant difference in the overall accuracy between T2W at AUROC 0.74 (95% CI 0.68-0.80), T2W+DWI at 0.76 (95% CI 0.71-0.82) and T2W+DWI+DCE at 0.77 (95% CI 0.71-0.82) (p=0.55). The AUROCs remained comparable using other definitions of clinically significant disease including UCL/Ahmed 2 (p=0.79), Gleason >/=3+4 (p=0.53) and Gleason >/=4+3 (p=0.53).

Using a 3T MRI, a high level of diagnostic accuracy can be achieved using T2W as a single parameter in men with a prior biopsy. However, such a strategy can lead to a higher rate of equivocal lesions.

Thiel-embalmed cadavers as a novel training model for ultrasound guided supine endoscopic combined intrarenal surgery.

BJU International

To evaluate Thiel-embalmed cadavers (TEC) as a training model for percutaneous nephrolihotomy (PCNL), more specifically for ultrasound (US) guided, supine, endoscopic combined intrarenal surgery (ECIRS). PCNL is a challenging procedure that requires specialized training and has a steep learning curve before reaching competence. As TEC have been shown to be a viable high-fidelity training model for upper and lower tract endoscopy, we aimed to evaluate TEC as a training model for PCNL.

Thirteen urologists (9 experienced endo-urologists, 4 fellows/residents) performed an US guided supine ECIRS procedure on a TEC. The model was evaluated by way of a questionnaire (5-point Likert scale). Descriptive statistical analysis was performed and results were graphically presented using divergent bar graphs.

US images were appreciated as lifelike in all aspects. Although distention of the collecting system was not ideal in 1 out of 3 cadavers, US visualization of the distended calyces during puncture was good. Skin penetration was more difficult and less realistic in TEC, while kidney puncture and dilation were deemed very realistic. Ureteral and collecting system anatomy and consistency are similar to real life, although the mucosa appeared paler. US needle guidance was perceived as excellent. Overall needle puncture assessment was realistic and useful as a training tool. Overall quality and satisfaction of TEC in US guided, supine ECIRS is good to excellent and comparable to a real-life procedure. Overall appropriateness of the TEC model was considered excellent for both initial and advanced supine PCNL training.

Despite the minor drawbacks of tough skin and non-ideal collecting system dilation during ureteroscopy, the TEC model is considered good to excellent as training model for US guided PCNL, in particular, US guided needle puncture of the kidney during supine ECIRS.

The seminal microbiome in health and disease.

Nature Reviews Urology

Owing to the fact that there are more microbial than human cells in our body and that humans contain more microbial than human genes, the microbiom...

Critical analysis of urethroplasty for male anterior urethral stricture: a single-center experience.

World Journal of Diabetes

Urethroplasty is the most effective treatment method for anterior urethral strictures, which constitute an important health concern for males. This study aims to investigate factors that may predict treatment failure following urethroplasty for anterior urethral strictures and evaluate outcomes of different urethroplasty techniques.

This retrospective study utilized univariate and multivariate analyses to identify factors affecting treatment success following different urethroplasty techniques performed by a single surgeon on male patients with anterior urethral strictures. Surgical outcomes of different urethroplasty techniques were evaluated individually.

Urethroplasty procedures performed on 244 patients with a mean age of 54 years and a mean stricture length of 4.7 cm produced a success rate of 79.1%. Multivariate analyses identified stricture length and number of previous internal urethrotomy procedures as factors predicting urethroplasty success (HR 1.265, 95% CI 1.129-1.416, p < 0.001 and HR 1.188, 95% CI 1.038-1.361, p = 0.013, respectively). The eight surgical techniques used by the surgeon produced success rates that varied between 50% and 86.2%.

Urethroplasty can offer satisfactory outcomes for anterior urethral strictures. Accordingly, a longer stricture length and greater number of previous internal urethrotomy procedures were associated with greater risk for urethroplasty failure. Moreover, urethroplasty techniques must be selected based on multifactorial evaluation and performed at experienced centers.

Effect of active versus passive void trials on time to patient discharge, urinary tract infection, and urinary retention: a randomized clinical trial.

World Journal of Diabetes

We sought to determine the effect of active versus passive voiding trials on time to hospital discharge and rates of urinary tract infection (UTI) and urinary retention (UR).

We performed a prospective, randomized trial comparing active (AVT) versus passive (PVT) void trials of inpatients requiring urethral catheter removal. Of 329 eligible patients, 274 were randomized to AVT (bladder filled with saline before catheter removal) or PVT (spontaneous bladder filling after catheter removal). Primary outcome was time to hospital discharge. Secondary outcomes were UTI (NSQIP criteria) and UR (requiring repeat catheterization) within 2 weeks of void trial.

The median time to void was 18 (5-115) versus 236 (136-360) min in the AVT and PVT groups, respectively (p < 0.0001). However, no difference was seen in comparison of the median time to hospital discharge between AVT [28.4 (13.6-69.3) h] and PVT [30.0 (10.4-75.6) h] cohorts, respectively (p = 0.93). Six (4.8%) and 13 (12.9%) patients developed UTI in the AVT and PVT groups, respectively (p = 0.03). Eleven (8.8%) and 12 (11.9%) patients developed UR in the AVT and PVT groups, respectively (p = 0.36).

Our study comparing AVT versus PVT demonstrated no difference in time to discharge despite a 3.6 h reduction in time to void associated with AVT. AVT was associated with a 63% reduction in UTI, with no difference seen in UR rates across cohorts. Given the reduction in UTI and technical advantages, our data suggest that AVT should be considered as a recommended technique for void trial protocol.

NCT02886143 (clinicaltrials.gov).

RELA is sufficient to mediate interleukin-1 repression of androgen receptor expression and activity in an LNCaP disease progression model.

Prostate

The androgen receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR messenger RNA (mRNA) levels and activity in AR-positive (AR+ ) PCa cell lines concomitant with the upregulation of prosurvival biomolecules. Thus, we contend that IL-1 can select for AR-independent, treatment-resistant PCa cells.

To begin to explore how IL-1 signaling leads to the repression of AR mRNA levels, we performed comprehensive pathway analysis on our RNA sequencing data from IL-1-treated LNCaP PCa cells. Our pathway analysis predicted nuclear factor kappa B (NF-κB) p65 subunit (RELA), a canonical IL-1 signal transducer, to be significantly active and potentially regulate many genes, including AR. We used small interfering RNA (siRNA) to silence the NF-κB family of transcription factor subunits, RELA, RELB, c-REL, NFKB1, or NFKB2, in IL-1-treated LNCaP, C4-2, and C4-2B PCa cell lines. C4-2 and C4-2B cell lines are castration-resistant LNCaP sublines and represent progression toward metastatic PCa disease, and we have previously shown that IL-1 represses AR mRNA levels in C4-2 and C4-2B cells.

siRNA revealed that RELA alone is sufficient to mediate IL-1 repression of AR mRNA and AR activity. Intriguingly, while LNCaP cells are more sensitive to IL-1-mediated repression of AR than C4-2 and C4-2B cells, RELA siRNA led to a more striking derepression of AR mRNA levels and AR activity in C4-2 and C4-2B cells than in LNCaP cells.

These data indicate that there are RELA-independent mechanisms that regulate IL-1-mediated AR repression in LNCaP cells and suggest that the switch to RELA-dependent IL-1 repression of AR in C4-2 and C4-2B cells reflects changes in epigenetic and transcriptional programs that evolve during PCa disease progression.