Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury.

AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment. CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.

National practice patterns and direct medical costs for prostate cancer in Korea across a 10 year period: a nationwide population-based study using a national health insurance database.

BACKGROUND: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. METHODS: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. RESULTS: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. CONCLUSIONS: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Changes in Adenosine Triphosphate and Nitric Oxide in the Urothelium of Patients with Benign Prostatic Hyperplasia and Detrusor Underactivity.

PURPOSE: We investigated changes in the levels of adenosine triphosphate and nitric oxide in the urothelium of men with detrusor underactivity and benign prostatic hyperplasia. MATERIALS AND METHODS: We prospectively enrolled in study 30 men who planned to undergo surgical treatment for benign prostatic hyperplasia. The 15 patients with a bladder contractility index less than 100 were assigned to the detrusor underactivity group while the 15 with a bladder contractility index more than 100 were assigned to the no detrusor underactivity group. Bladder mucosal specimens were collected at surgical prostate resection, and adenosine triphosphate and endothelial nitric oxide synthase were analyzed in these specimens. The levels of adenosine triphosphate and endothelial nitric oxide synthase were compared between the 2 groups. The correlation of urodynamic parameters with adenosine triphosphate and endothelial nitric oxide synthase was assessed in all patients. RESULTS: Mean ± SEM endothelial nitric oxide synthase did not significantly differ between the detrusor underactivity and no underactivity groups (3.393 ± 0.969 vs 1.941 ± 0.377 IU/ml, p = 0.247). However, the mean level of adenosine triphosphate in the detrusor underactivity group was significantly lower than in the no detrusor underactivity group (1.289 ± 0.320 vs 9.262 ± 3.285 pmol, p = 0.011). In addition, in all patients adenosine triphosphate positively correlated with the bladder contractility index (r = 0.478, p = 0.018) and with detrusor pressure on maximal flow (r = 0.411, p = 0.046). CONCLUSIONS: Adenosine triphosphate was significantly decreased in the urothelium in men with detrusor underactivity and benign prostatic hyperplasia, reflecting the change in detrusor function.

Hyaluronic acid-carboxymethylcellulose reduced postoperative bowel adhesions following laparoscopic urologic pelvic surgery: a prospective, randomized, controlled, single-blind study.

BACKGROUND: To assess the anti-adhesive effect of treatment with hyaluronic acid-carboxymethylcellulose following laparoscopic radical prostatectomy. METHODS: This was a randomized, controlled, single-blind, parallel-group study using hyaluronic acid-carboxymethylcellulose in patients who underwent laparoscopic radical prostatectomy. Sixty patients were enrolled in the study. All patients were randomly assigned to either the hyaluronic acid-carboxymethylcellulose treatment group (n = 30) or the control group (n = 30). Viscera slide ultrasounds and plain X-rays were obtained at enrollment (V0), postoperative week 12 (V1), and 24 (V2). The primary end point was the difference in the excursion distance in the viscera slide ultrasound between V0 and V2. RESULTS: A total of 50 patients completed this study. The average excursion distance at V2 in the experimental group (n = 25) was significantly longer than in the control group (n = 25, 2.7 ± 1.2 vs. 1.3 ± 1.0 cm, respectively; p < 0.001). The differences in the V0 and V2 excursion distances were significantly higher in the control group than in the experimental group (1.48 ± 1.5 vs. 2.9 ± 1.2 cm, respectively; p < 0.001). None of patients showed adverse events associated with the use of hyaluronic acid-carboxymethylcellulose. CONCLUSION: This randomized study demonstrated that hyaluronic acid-carboxymethylcellulose treatment resulted in a reduction in bowel adhesion to the abdominal wall after laparoscopic pelvic surgery and had good clinical safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02773251 Date: May 12, 2016.

Evaluation of female overactive bladder using urodynamics: relationship with female voiding dysfunction.

PURPOSE: To investigate the role of urodynamic study (UDS) in female patients with overactive bladder (OAB) analyzing the relationship between OAB symptoms and female voiding dysfunction (FVD). MATERIALS AND METHODS: We analyzed the clinical and urodynamic data of 163 women with OAB symptoms. OAB symptoms were categorized as dry and wet. FVD was described as detrusor underactivity (DUA), which was defined as a maximum flow rate (Qmax) of ≤ 15 mL/s associated with a detrusor pressure at Qmax (PdetQ max) of ≤ 20 cmH2O, along with bladder outlet obstruction (BOO), which was defined as a Qmax of ≤ 15 mL/s with a PdetQ max of > 20 cmH2O. Clinical and urodynamic results were compared between patients with dry and wet symptoms and between those with and without FVD. RESULTS: 78 (47.9%) had dry, and 85 (52.1%) had wet symptoms. The entire group had a relatively low Qmax (15.1 ± 6.6 mL/s) and relatively high number of BOO (42.9%, 70/163) and DUA (8.6%, 14/163). A significantly higher number of patients with wet symptoms had detrusor overactivity compared to those with dry, as detected by the UDS (p < 0.05). No significant differences were found in BOO and DUA number between dry and wet groups. Further, the international prostate symptom score did not different significantly between patients with and without FVD. CONCLUSION: A significant number of women with OAB had voiding dysfunction. However, the OAB symptoms themselves were not useful for predicting the presence of FVD. Therefore, UDS may be necessary for accurate diagnosis in women with OAB symptoms.

Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats.

PURPOSE: To investigate transient receptor potential vanilloid 4 (TRPV4) expression and the effects of ruthenium red (RR)-TRPV antagonist-on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO). METHODS: Rats were randomly assigned to 3 groups. The control group (n = 10) included sham-operated rats. The BOO-group without RR (n = 15) and BOO-group with RR (n = 15) underwent partial BOO surgery. Three weeks postoperatively, cystometrography was performed in all rats. After confirming DO, RR was instilled intravesically in the BOO-group with RR. Urodynamic parameters were investigated, including contraction interval (CI) and contraction pressure (CP). TRPV4 expression was evaluated through immunofluorescence staining and western blotting. RESULTS: The BOO-group without RR had significantly shorter CI and significantly higher CP compared to the control. In the BOO-group with RR, CI was significantly longer compared to the BOO-group without RR. However, change in CP between BOO-group without and with RR was not significantly different. Immunofluorescence staining showed that TRPV4 was localized in the urothelium and detrusor muscles. TRPV4 immunofluorescence signals were increased in the urothelium and detrusor muscle in BOO-group without RR, compared with the control. In western blot analysis, immunoreactive bands indicating expression of TRPV4 were detected in the urothelium and detrusor muscle, and those were significantly increased in the BOO-group without RR compared with the control in the urothelium and detrusor muscle. CONCLUSIONS: TRPV4 plays an important role in the pathophysiology of DO, and RR has a beneficial effect on DO associated with BOO.

The influence of depression, anxiety and somatization on the clinical symptoms and treatment response in patients with symptoms of lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

This is the first study to investigate the influence of depression, anxiety and somatization on the treatment response for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the Korean versions of the International Prostate Symptom Score (IPSS), the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the PHQ-15. The primary endpoint was a responder rate defined by the total score of IPSS (≤ 7) at the end of treatment. The LUTS/BPH severity was significantly higher in patients with depression (whole symptoms P = 0.024; storage sub-symptom P = 0.021) or somatization (P = 0.024) than in those without, while the quality of life (QOL) was significantly higher in patients with anxiety (P = 0.038) than in those without. Anxious patients showed significantly higher proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those without, while somatic patients had a trend toward having more non-responders (OR, 2.552, P = 0.067). Our exploratory results suggest that depression, anxiety and somatization may have some influences on the clinical manifestation of LUTS/BPH. Further, anxious patients had a lower response to treatment in patients with LUTS/BPH. Despite of limitations, the present study demonstrates that clinicians may need careful evaluation of psychiatric symptoms for proper management of patients with LUTS/BPH.

The predictor analysis of response to routine treatment in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: This study tried to test predictors of response to routine treatment in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). METHODS: Subjects were evaluated at baseline and at week 12 following routine treatment for LUTS/BPH using the Korean version of the International Prostate Symptom Score (IPSS) to measure the severity of LUTS/BPH. Demographics and various clinical variables were analyzed by regression analysis. RESULTS: Ninety three patients received routine treatment for LUTS/BPH for 12 weeks in a naturalistic treatment setting. None of demographics and clinical variables was different between responders and non-responders. According to multivariate regression analysis, the presence of anxiety (OR=0.203), lower improvement in the GAD-7 total score (OR=0.755) and lower improvement in the PHQ-15 total score (OR=0.811) were independent predictors of treatment response after 12 weeks routine treatment. CONCLUSIONS: We found the positive association of improvement in anxiety and somatization with treatment response, while presence of anxiety was negatively associated with treatment response, in patients with LUTS/BPH. However, additional studies with adequate power and improved designs are necessary to support the present findings.

Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E(2) (PGE(2)) in women with overactive bladder (OAB) following anticholinergic treatment. METHODS: A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE(2) levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared. RESULTS: Urinary NGF and PGE(2) levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE(2) levels were not significantly different between pre- and post-treatment in either group. CONCLUSIONS: NGF and PGE(2) have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.

Lower urinary tract symptoms in benign prostatic hyperplasia patients: orchestrated by chronic prostatic inflammation and prostatic calculi?.

OBJECTIVE: This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. RESULTS: There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. CONCLUSIONS: Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms.

Outcomes of Artificial Urinary Sphincter Implantation in Patients with Detrusor Underactivity and Postprostatectomy Incontinence.

PURPOSE: There is insufficient evidence for postoperative outcomes of artificial urinary sphincter (AUS) implantation for postprostatectomy incontinence (PPI) with detrusor underactivity (DU). Thus, we assessed the impact of preoperative DU on the outcomes of AUS implantation for PPI. MATERIALS AND METHODS: Medical records of men who underwent AUS implantation for PPI were reviewed. Patients who had bladder outlet obstruction surgery before radical prostatectomy or AUS-related complications that required revision of AUS within three months were excluded. Patients were divided into two groups based on the preoperative urodynamic study including pressure flow study, a DU group, and a non-DU group. DU was defined as a bladder contractility index less than 100. The primary outcome was postoperative postvoid residual urine volume (PVR). The secondary outcomes included maximum flow rate (Qmax), postoperative satisfaction, and international prostate symptom score (IPSS). RESULTS: A total of 78 patients with PPI were assessed. The DU group consisted of 55 patients (70.5%) and the non-DU group comprised 23 patients (29.5%). Qmax was lower in the DU group than in the non-DU group and PVR was higher in the DU group as per a urodynamic study before AUS implantation. There was no significant difference in postoperative PVR between the two groups, although the Qmax after AUS implantation was significantly lower in the DU group. While the DU group showed significant improvements in Qmax, PVR, IPSS total score, IPSS storage subscore, and IPSS quality of life (QoL) score after AUS implantation, the non-DU group showed postoperative improvement in IPSS QoL score. CONCLUSION: There was no clinically significant impact of preoperative DU on the outcome of AUS implantation for PPI; thus, surgery can be safely performed in patients with PPI and DU.

Changes in transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 in patients with lower urinary tract dysfunction.

PURPOSE: We investigated the association between transient receptor potential vanilloid (TRPV) expression in human urothelium tissue and lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: We prospectively enrolled men who planned to undergo surgical treatment for benign prostatic obstruction to analyze TRPV1 and TRPV4 expression in the urothelium using enzyme-linked immunosorbent assay and immunofluorescence staining. Patients were divided into two groups based on urodynamics: the detrusor underactivity (DU) group and the non-DU group. Levels of TRPV1 and TRPV4 were compared between the two groups. We also divided patients into two groups according to degree of subjective urinary urgency symptoms using a 5-point urinary sensation scale and compared the differences in TRPV1 and TRPV4 levels between the two groups. The correlations between urodynamic parameters with TRPV1 or TRPV 4 in all patients were also analyzed. RESULTS: The levels of TRPV1 and TRPV 4 were not significantly different between the DU group (n=10) and the non-DU group (n=11). When we divided the patients according to degree of subjective urgency, the level of TRPV1 was not significantly different between the urgency group (n=10) and the non-urgency group (n =11), but the level of TRPV4 was significantly increased in the urgency group (p=0.029). There was no significant correlation between the level of TRPV1 or TRPV4 and urodynamic parameters in any patients. CONCLUSIONS: TRPV4 could be a useful diagnostic biomarker for patients with LUTD.

Correlation Between Nitric Oxide and Urodynamics in Men With Bladder Outlet Obstruction.

PURPOSE: To investigate the correlation between nitric oxide (NO) and urodynamics in men with bladder outlet obstruction (BOO) by analyzing nitric oxide synthase (NOS) in the urothelium. METHODS: We prospectively enrolled 25 men who planned to undergo surgical treatment for benign prostatic obstruction and identified as BOO in the preoperative urodynamics. Bladder tissue was taken during surgical prostate resection. Expressions of endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) in the urothelium were analyzed, and their correlation with urodynamic parameters was also assessed in all patients. We also compared the expressions of eNOS, iNOS, and nNOS between BOO with detrusor underactivity (DU) group and BOO without DU group. RESULTS: In all patients, the level of eNOS positively correlated with maximal flow rate and with maximum cystometric capacity (MCC). The level of iNOS positively correlated with MCC. nNOS levels were positively correlated with detrusor pressure at maximal flow and with bladder contractility index in all patients. The level of eNOS, iNOS, and nNOS did not significantly differ between BOO without DU group and BOO with DU group. CONCLUSION: This study suggests that NO was correlated with bladder dysfunction in men with BOO. Particularly, nNOS may reflect the change in detrusor function.

The incidence of testicular torsion and testicular salvage rate in Korea over 10 years: A nationwide population-based study.

PURPOSE: We performed a nationwide epidemiological study of testicular torsion using the National Health Insurance System database for the entire male population of Korea. MATERIALS AND METHODS: Age, sex, socioeconomic status, regional information, and diagnostic codes were retrieved from January 2009 to December 2019. To clearly identify the diagnosis of testicular torsion, patients who had not undergone orchiectomy or orchiopexy were excluded from the study. Multivariable logistic regression models were used to analyze the association between demographic characteristics and testicular loss. RESULTS: The overall incidence of testicular torsion in males was 2.02 cases per 100,000 person-years and 6.99 cases per 100,000 person-years in males under 19 years of age. Testicular torsion most commonly occurred either in infancy or adolescence. The total testicular salvage rate was 75.22% and highest in children at 79.91%. The rate of orchiectomy was high in infancy and in the oldest patients. We determined that age distribution was related to the risk of testicular loss. CONCLUSIONS: This study is the first nationwide epidemiological study of testicular torsion, which contains the entire Korean population. Although the testicular salvage rate in Korea was higher compared to other countries, it is necessary to educate males under 19 years of age on the seriousness of acute testicular pain to minimize the possibility of testicular loss.

Comparison of alpha-blocker, extracorporeal magnetic stimulation alone and in combination in the management of female bladder outlet obstruction.

INTRODUCTION AND HYPOTHESIS: To determine the effects of alpha-blocker, extracorporeal magnetic innervations (ExMI) alone and combination treatment on female bladder outlet obstruction (BOO). METHODS: Sixty women with BOO were divided into three groups according to the treatment. After 3 months, the clinical outcomes were evaluated by clinical examination, international prostatic symptom score (IPSS), quality of life (QOL), 3-day voiding diary, uroflowmetry and post-void residual. RESULTS: At 3 months, symptom improvement was 52.6% in alpha-blocker monotherapy (group I), 50.0% in ExMI monotherapy (group II), and 57.1% in combination therapy (group III). Maximum flow rate increased and total IPSS decreased significantly in all groups (p < 0.05). Storage symptom subscore was more reduced in groups II and III and QOL improved significantly in group III (p < 0.05) CONCLUSIONS: This study demonstrates that both alpha-blocker and ExMI were effective in female BOO, and ExMI may be more effective for improving storage symptoms.

Impact of age and metabolic syndrome-like components on prostate cancer development: a nationwide population-based cohort study.

BACKGROUND: Because of the contradictory results, more epidemiologic data is needed to determine if metabolic syndrome is a risk factor for developing prostate cancer. This study investigated whether metabolic syndrome-like components affect the incidence of prostate cancer in a Korean population. METHODS: Men over 50 years of age who underwent health examinations in 2009 were followed until December 2015 (n=1,917,430) using National Health Insurance System data. Subjects were divided into three groups according to the number of metabolic syndrome-like components. The predictive accuracy of age for prostate cancer was assessed by the Youden index and multivariate adjusted Cox regression analysis was used to analyze the effect of metabolic syndrome-like components on prostate cancer development. RESULTS: The risk of prostate cancer increases with age, and the best cutoff age for prostate cancer detection was 62 years (the maximum value of the Youden index). When stratified by the number of metabolic syndrome-like components, the age with the highest Youden index of each group is still 61 or 62 years. In multivariate adjusted Cox regression analysis, there was no statistically significant difference in the incidence rate among the non-component group, the group with 1 or 2 components, and the group with ≥3 components. CONCLUSIONS: The current study found that there was no statistically significant association between metabolic syndrome and prostate cancer development in a Korean population. However, results of this study should be interpreted with consideration due to several limitations including the diversity of definitions of metabolic syndrome components.

Trends in End-of-Life Resource Utilization and Costs among Prostate Cancer Patients from 2006 to 2015: A Nationwide Population-Based Study.

PURPOSE: The purpose of this study was to evaluate end-of-life resource utilization and costs for prostate cancer patients during the last year of life in Korea. MATERIALS AND METHODS: The study used the National Health Information Database (NHIS-2017-4-031) of the Korean National Health Insurance Service. Healthcare claim data for the years 2002 through 2015 were collected from the Korean National Health Insurance System. Among 83,173 prostate cancer patients, we enrolled 18,419 after excluding 1,082 who never claimed for the last year of life. RESULTS: From 2006 to 2015, there was a 3.2-fold increase the total number of prostate cancer decedents. The average cost of care during the last year of life increased over the 10-year period, from 14,420,000 Korean won to 20,300,000 Korean won, regardless of survival time. The cost of major treatments and medications, other than analgesics, was relatively high. Radiologic tests, opioids, pain control, and rehabilitation costs were relatively low. Multiple regression analysis identified age and living in rural area as negatively associated with prostate cancer care costs, whereas income level and a higher number of comorbidities were positively associated. CONCLUSIONS: Expenditure of prostate cancer care during the last year of life varied according to patient characteristics. Average costs increased every year. However, the results suggest underutilization of support services, likely due to lack of alternative accommodation for terminal prostate cancer patients. Further examination of patterns of utilization of healthcare resources will allow policymakers to take a better approach to reducing the burden of prostate cancer care.

Changes in uroplakin expression in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome.

Purpose: We evaluated changes in the expression of uroplakin (UP) in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and Methods: Bladder samples were collected from 19 patients with ulcerative IC/BPS who were treated with augmentation ileocystoplasty and from 5 control patients. Frequency-volume charts, the pain visual analogue scale (VAS), and the O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI) were used to evaluate the patients' symptoms preoperatively. The expression levels of UP-Ib and UP-III in the urothelium were compared between the IC/BPS patients and control patients. Results: Sixteen women and three men with IC/BPS were evaluated. Their values for preoperative mean voiding frequency, number of nocturia episodes, and functional bladder capacity as recorded in frequency-volume charts were 21.1±12.8, 5.9±4.2, and 151.1±62.7 mL, respectively. The mean pain VAS, ICSI, and ICPI scores were 8.4±1.3, 17.7±2.2, and 14.7±1.8, respectively. Immunofluorescence staining showed that UP-Ib and UP-III were localized in the urothelium. Upon Western blot analysis, the expression of UP-III was significantly increased in the IC/BPS group compared with the control group. However, expression of UP-Ib did not differ significantly between the IC/BPS and control groups. Conclusions: UP-III was significantly upregulated in patients with ulcerative IC/BPS. UP-III is a potential biomarker for the diagnosis of ulcerative IC/BPS.

An open-label, single-arm pilot study to evaluate the efficacy of daily low dose tadalafil on depression in patients with erectile dysfunction.

BACKGROUND: Many studies have reported not only that depression and antidepressant medications can cause erectile dysfunction (ED), but also that having ED may increase the risk of depression. We investigated the effect of a daily low dose of a phosphodiesterase (PDE) type 5 inhibitor (tadalafil, 5 mg) on depression and levels of brain-derived neurotrophic factor (BDNF) in patients with ED. METHODS: Ten male patients with at least a 3-month history of ED [International Index of Erectile Function (IIEF)-5 score ≤21] and depression [the Korean version of the Patient Health Questionnaire (PHQ)-9 score ≥5] were analyzed in this study. The subjects were prescribed a low dose of a PDE5 inhibitor (tadalafil 5 mg) once daily for 8 weeks. The survey questionnaires were performed using the PHQ-15 and the PHQ-9 before and after administration of 8 weeks of tadalafil. Blood samples used for measuring serum BDNF levels were taken and measured at baseline and after 8 weeks of treatment. RESULTS: The mean changes in the PHQ-9 and PHQ-15 scores were 3.60±3.27 and 2.00±2.98, respectively. Analyses of the mean changes in the PHQ-9 scores revealed that the depressive symptoms of the subjects were significantly improved after administration of eight weeks of tadalafil (P<0.05). And, there was also a statistically significant increase in the PHQ-15 scores (P<0.05). Serum levels of BDNF were higher after tadalafil treatment compared to before treatment; however, this difference was not statistically significant. CONCLUSIONS: The results of this prospective, clinical study suggest that daily low dose tadalafil may have a potential role in the treatment of depression in patients with ED.

The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment.

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.