Detrusor Underactivity in Men with Bladder Outlet Obstruction.

Detrusor underactivity (DU) and bladder outlet obstruction (BOO) are both common troublesome causes of lower urinary tract symptoms (LUTS) and often impact on quality of life simultaneously in men. This article aims to focus on DU with BOO in male patients. METHODS: Original articles concerning DU with BOO were identified through literature research from PubMed and EMBASE database. We selected 38 articles in our review, including those concerning pathophysiology, evaluation, treatment and predictors for a successful BOO surgery for DU. RESULTS: DU from BOO can result from several pathophysiological mechanisms. Although urodynamic study (UDS) is considered as a precise method to diagnose DU and BOO, there are some previous studies which proposed a non-invasive method to identify DU related to BOO. The treatment goal of DU is restoring bladder contractility using medication or surgery. Releasing outlet obstruction and resistance is the main strategy to restore bladder contractility when medication to directly increase bladder contractility has had limited efficacy. CONCLUSIONS: DU from BOO is poorly understood and is largely under-researched. The etiology and pathophysiology still need to be evaluated. Effective and safe medication to restore bladder contractility is also lacking. It remains valuable to perform further research to reveal the unknown aspects of DU.

High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.

BACKGROUND: Ubiquitin-mediated protein degradation has been reported to be involved in regulating the activity of oncoproteins and tumor suppressors. Dysfunction or dysregulation of the ubiquitin-proteasome system may induce tumorigenesis. Deubiquitinase ubiquitin-specific protease 2a (USP2a) has been reported to regulate cell growth or death and is involved in the pathogenesis of various diseases, including cancers. However, the role of USP2a in upper tract urothelial carcinoma (UTUC) has not been investigated yet. The goal of this study was to evaluate the clinical significance of USP2a expression in UTUC. MATERIALS AND METHODS: A total of 110 UTUC cases were included in this study. USP2a expression level was evaluated through immunohistochemistry staining, and the correlation of USP2a expression level with both clinical and pathologic variables was analyzed. RESULTS: High USP2a expression level was observed in 48 (43.6%) cancer specimens. USP2a expression level was significantly correlated with tumor stage (P=0.001), grade (P=0.033), and tumor recurrence (P=0.008). High USP2a expression level was correlated with poor disease-free survival (P=0.005) and cancer-specific survival (P<0.001). In addition, high USP2a expression level was an independent predictor of poor disease-free survival (hazard ratio=2.31; P=0.007) and cancer-specific survival (hazard ratio=5.49; P=0.009). CONCLUSIONS: This study indicated that USP2a protein expression level may be a potential biomarker for predicting UTUC patient survival. Further prospective studies are needed to investigate the role of USP2a in UTUC progression.

MicroRNA-375-3p Suppresses Upper Tract Urothelial Carcinoma Cell Migration and Invasion via Targeting Derlin-1.

Little is known regarding the molecular characterization of upper tract urothelial carcinoma (UTUC). Novel therapeutic targets and prognostic predictors are imminent. In the present study, we aim to examine the oncogenic function and molecular mechanism of Derlin-1 in UTUC. Derlin-1 overexpression is significantly associated with poor prognosis in patients with UTUC. In vitro, knockdown or over-expression of Derlin-1 markedly regulated UTUC cell invasion and migration. We further discovered miR-375-3p suppresses cell invasion and migration by inversely regulating Derlin-1 and blocking EMT in UTUC cells. Taking this together, miR-375-3p functions as a tumor suppressive microRNA by directly targeting Derlin-1 and blocking epithelial-mesenchymal transition (EMT) in UTUC.

Newly designed solid coupling medium for reducing trapped air pockets during extracorporeal shock wave lithotripsy_ a phantom study.

INTRODUCTION: Air pockets between the lithotripter head and body surface are almost inevitably generated when applying a handful of gel onto the contact portion of the treatment head and that on the patient's skin during coupling procedure. These air pockets can compromise the transmission of acoustic energy of shock wave and may significantly affect efficacy of stone disintegration. Comparing to conventional gel, this study aims to investigate efficacy of stone disintegration by using a proprietary isolation-coupling pad ("icPad") as the coupling medium to reduce trapped air pockets during ESWL procedure. METHOD: In this phantom study, Dornier lithotripter (Delta-2 RC, Dornier MedTech Europe GmbH Co., Germany) was used with a proprietary gel pads (icPad, Diameter = 150 mm, Thickness = 4 mm and 8 mm). The lithotripter was equipped with inline camera to observe the trapped air pockets between the contact surface of the lithotripter head. A testing and measuring device were used to observe experimental stone disintegration using icPad and semi-liquid gel. The conventional semi-liquid gel was used as control for result comparison. RESULTS: The stone disintegration rate of icPad 4 mm and 8 mm after 200 shocks of energy at level 2 were significantly higher than that of the semi-liquid gel (disintegration rate 92.3%, 85.0% vs. 45.5%, respectively, p < 0.001). The number of shocks for complete stone disintegration by icPad of 4 mm and 8 mm at the same energy level 2 were significantly lower than that of the semi-liquid gel (the number of shocks 242.0 ± 13.8, 248.7 ± 6.3 vs. 351.0 ± 54.6, respectively, p = 0.011). Furthermore, quantitative comparison of observed air pockets under Optical Coupling Control (OCC) system showed that the area of air pockets in semi-liquid group was significantly larger than that of the group using icPad (8 mm) and that of the group using icPad (8 mm) after sliding (332.7 ± 91.2 vs. 50.3 ± 31.9, 120.3 ± 21.5, respectively, p < 0.05). CONCLUSION: The advantages of icPad includes: (1) reduced the numbers of shock wave and increased stone disintegration rate due to icPad's superior efficacy; (2) significantly reduce trapped air pockets in ESWL coupling. Due to the study limitation, more data are needed to confirm our observations before human trials.

A rare noncancerous but life-threatening tumor in urinary bladder.

IMT is a rare but sometimes life-threatening tumor. Although presenting with muscle invasion, local surgical resection with TURBT and close follow-up are adequate with bladder function and life quality preservation compared to partial cystectomy.

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation.

Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

5α-reductase inhibitors impact prognosis of urothelial carcinoma.

BACKGROUND: 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. METHODS: The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. RESULTS: Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1). CONCLUSIONS: Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.