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Introduction Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). Materials and methods We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at − 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson’s correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. Results We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman’s correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P Conclusion Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model. Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies. Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder. Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

The metabolic syndrome was associated with bladder cancer in the previous studies. However, there have no large-scale cohort studies to elucidate the relationship between metabolic syndromes and urothelial carcinoma including urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC). We analyze a population-based cohort study by using physical examination data and diagnosis of UC from the Taiwan Cancer Registry Database. Differences in demographic and clinical characteristics among UTUC and non-UTUC groups, UBUC and non-UBUC groups were compared. Odds ratios (ORs) for determining risk factors were estimated through the multiple logistic regression model. A total of 557,063 records for 211,319 participants which consisted of 31 UTUC and 309 UBUC met the eligibility criteria in this study. Our results showed that female are more likely to develop UTUC than male. As opposed to UTUC, male are more likely to develop UBUC than female. It also showed that participants smoked or chewed betel quid daily are more likely to develop UBUC. Age and estimated glomerular filtration rate (eGFR) are significantly increased the risk of developing UTUC. The association between the eGFR and risk of UTUC is stronger (P

Eugenosedin-A (Eu-A) has been shown to protect against hyperglycemia- and hyperlipidemia-induced metabolic syndrome. We investigated the relationship of KATP channel activities and insulin secretion by Eu-A in vitro in pancreatic β-cells, and examined the effect of Eu-A on streptozotocin (STZ)/nicotinamide (NA)-induced type 2 diabetes mellitus (T2DM) in vivo. We isolated pancreatic islets from adult male Wistar rats (250–350 g) and identified pancreatic β-cells by the cell size, capacitance and membrane potential. Perforated patch-clamp and inside-out recordings were used to monitor the membrane potential (current-clamp mode) and channel activity (voltage-clamp mode) of β-cells. The membrane potential of β-cells was raised by Eu-A and reversed by the KATP channel activator diazoxide. Eu-A inhibited the KATP channel activity measured at − 60 mV and increased the intracellular calcium concentration ([Ca2+]i), resulting in enhanced insulin secretion. Eu-A also reduced Kir6.2 protein on the cell membrane and scattered in the cytosol under normal glucose conditions (5.6 mM). In our animal study, rats were divided into normal and STZ/NA-induced T2DM groups. Normal rats fed with regular chow were divided into control and control+Eu-A (5 mg/kg/day, i.p.) groups. The STZ/NA-induced diabetic rats fed with a high-fat diet (HFD) were divided into three groups: T2DM, T2DM+Eu-A (5 mg/kg/day, i.p.), and T2DM+glibenclamide (0.5 mg/kg/day, i.p.; a KATP channel inhibitor). Both Eu-A and glibenclamide decreased the rats’ blood glucose, prevented weight gain, and enhanced insulin secretion. We found that Eu-A blocked pancreatic β-cell KATP channels, caused membrane potential depolarization, and stimulated Ca2+ influx, thus increasing insulin secretion. Furthermore, Eu-A decreased blood glucose and increased insulin levels in T2DM rats. These results suggested that Eu-A might have clinical benefits for the control of T2DM and its complications.

Aims: To evaluate the effects of low intensity extracorporeal shock wave therapy (LiESWT) on stress urinary incontinence (SUI). Methods: This investigation was a multicenter, single-blind, randomized controlled trial study. 60 female SUI patients were randomly assigned to receive LiESWT with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/second, once weekly for 4-week (W4) and 8-week (W8), or an identical sham LiESWT treatment without energy transmission. The primary endpoint was the changes in urine leakage as measured by pad test and validated standardized questionnaires. While the secondary endpoint was the changes in 3-day urinary diary among the baseline (W0), the W4 and the W8 of LiESWT, and 1-month (F1), 3-month (F3) and 6-month (F6) follow-up after LiESWT. Results: The results showed that 4-week LiESWT could significantly decrease urine leakage based on pad test and validated standardized questionnaire scores, as compared to the sham group. Moreover, 4-week LiESWT could significantly reduce urine leakage, but increase urine volume and attenuate urgency symptom, which showed meaningful and persistent improvement at W8, F1, F3 and F6. Furthermore, validated standardized questionnaire scores were significantly improved at W4, W8, F1, F3 and F6 as compared to the baseline (W0). Conclusions: 8-week LiESWT could attenuate SUI symptoms on physical activity, reduce urine leakage and ameliorate overactive bladder symptoms, which implied that LiESWT significantly improved the quality of life. Our findings suggested that LiESWT could serve as a potentially novel and non-invasive treatment for SUI.

The aims of the present study were to (1) analyse preoperative computed tomography (CT) parameters, (2) investigate whether obesity and CT parameters affect surgical outcomes in patients undergoing LESS lateral retroperitoneal adrenalectomy, and (3) further establish the optimal cutoff point of CT parameters for tolerable operating time. Between January 2010 and August 2016, patients who underwent LESS adrenalectomy through the retroperitoneal approach in our hospitals were included. Patients’ demographic data, preoperatively measured CT parameters (the depth and horizontal width to the adrenal gland in the axial view of abdominal CT, the vertical height in the coronal view of CT, and the angle of the depth and horizontal width), and intraoperative (operative time and blood loss) and postoperative (hospital stay and complications) parameters were retrospectively reviewed. Linear regression was performed to determine factors that potentially affect surgical outcomes. In 116 patients, depth was the only CT parameter associated with surgical outcomes. Large depth (P = 0.005; 95% CI 1.739–9.256) and high BMI (P = 0.012; 95% CI 0.357–2.851) were factors significantly associated with longer operative time. The area under the ROC curve for the depth was 0.69 (P = 0.002), and the cutoff point 10.48 cm may be the tolerable operating time. Our results suggest a depth limit of 10.48 cm for the optimal prediction of operating time less than 90 min; although obese patients and deeper adrenal glands had longer operative time, LESS adrenalectomy could be performed in the obese patients without increased blood loss, prolonged hospital stay, or increased pain.

Applying low-intensity extracorporeal shockwave therapy (LI-ESWT) has been reported to improve symptoms of refractory chronic pelvic pain syndrome (CPPS) in short-term follow-up. This study aims to demonstrate the effect of LI-ESWT on refractory CPPS over the span of a 12-month follow-up.This was an open-label, single-arm prospective study. LI-ESWT consisted of 3000 shock waves once weekly for 4 weeks (Duolith SD1 T-Top) were applied. Clinical symptoms were re-assessed at 1, 3, 6, and 12 months using NIH-CPSI score, visual analog scale, 5-item version of the International Index of Erectile Function and International Prostate Symptom Score.Thirty-one of the 43 patients enrolled had a successful response at the 1-month follow up after the treatment. Twenty-six of the 31 patients who responded successfully to LI-ESWT at the 1-month follow-up, maintained their response at the 6- and 12-month follow-up. The existence of psychosocial disorder at the baseline characteristics analysis was the only potential factor that may hinder the effectiveness of LI-ESWT.LI-ESWT has shown to be a safe and effective therapy for CPPS patients at the long-term follow-up. History of psychological disorders might be a significant predictor of a successful response.

Introduction: The aim of this study is to explore whether male patients diagnosed of congenital collagen diseases had higher risk of occurrence inguinal hernia than patients who do not had these diseases.Method: Data were collected from National Health Insurance Research Database (NHIRD) of Taiwan retrospectively. 1801 male patients who diagnosed of congenital collagen disease by using ICD-9 CM diagnostic code was the study cohort, and in the other hand, after propensity score matching, 6493 man without congenital collagen disease were enrolled as control group. The primary endpoint was receiving inguinal hernia repair during observation period.Result: During median 133.9 months follow-up period, the risk of inguinal hernia in collagen cohort was significantly higher than the control group (HR = 2.237, 95% CI:1.646–3.291, p Conclusion: Asian men, regardless of age, with congenital collagen disease are at the risk of developing inguinal hernia. Detailed physical examination and well patient education should be performed while facing these patients.

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.

Introduction: Urinary incontinence (UI) is more prevalent in elderly populations with dementia than those without dementia. Alzheimer’s disease (AD) is the most common cause of dementia. Urge UI, the most common type of UI in AD patients, causes more morbidity and mortality. However, it is inconvenient to obtain the report of urodynamic study from AD patient to diagnose urinary incontinence. Nevertheless, it is easier to obtain subjective or objective questionnaires from the patients or the caregivers. The data collected from the questionnaires are used to evaluate if severity of dementia is associated with urge UI and other lower urinary tract symptoms (LUTs). Patients and Methods: A total of 43 AD patients were enrolled in this study, all of whom were checked post-void residual (PVR) urine amount by sonography after voiding. The severity of dementia was evaluated by questionnaire including Cognitive Abilities Screening Instrument (CASI), Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and Clinical Dementia Rating Sub-of-Box (CDR-SB). The LUTs were assessed with International Consultation of Incontinence Questionnaire (ICIQ) and Overactive bladder symptom scores (OABSS) questionnaire. Independent t test and Pearson’s correlation analysis were calculated. Results: The average age in both AD with/without urge UI patients is 78 years old. The scores of CDR-SB, OABSS and ICIQ are significantly different in these 2 groups (p = 0.023, p = 0.003, p = 0.001; respectively). However, the neurophysiological scores of CASI, MMSE, CDR, CDR-SB is not correlated with OABSS (r = 0.047, p = 0.382; r = 0.074, p = 0.317; r = 0.087, p = 0.288; r = 0.112, p = 0.237; respectively). Interestingly, if we separate each individual symptom of OAB, there is a significant correlation between CDR-SB and urge UI score (r = 0.314, p = 0.023). Conclusions: Higher lower urinary tract symptom scores are noted in AD patients with urge UI. The CDR-SB score is highly correlated with urge UI in AD patients.

Simple Summary On the basis of the efficacy and tolerable safety profiles of immune checkpoints inhibitors (ICIs) in second-line metastatic urothelial carcinoma (mUC) patients, some emerging clinical trials focus on the first-line treatment. Thus, we conducted a network meta-analysis (NMA) to assess and compare the response and toxicity of ICIs in naïve-chemotherapy mUC setting. According to our results, combination therapy (either ICIs plus chemotherapy (CTX) or ICIs plus ICIs) had a higher priority in terms of overall survival. Concerning monotherapy, ICIs are not inferior to CTX in terms of OS. In view of the adverse effect, ICIs are very tolerable, and combination therapy did not lead to a higher incidence of grade 3–5 AEs when compared with CTX. Abstract Immune checkpoints inhibitors (ICIs) were considered as second-line treatments in metastatic urothelial carcinoma (mUC) based on better survival benefit and safety profile than chemotherapy (CTX). We aimed to assess different ICIs regimens in the efficacy and safety for front-line treatments in mUC patients. A comprehensive literature search was performed and Phase II-III randomized controlled trials (RCTs) on ICIs for patients with mUC were included. The outcome was evaluated by overall survival (OS), progression of free survival (PFS), objective response rate (ORR), and grade 3–5 adverse events. Network meta-analysis was used to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were applied to rank the included treatments for each outcome. Results: The survival benefit of a single ICI was non-inferiority to chemotherapy (CTX). Although no superior effects were indicated, combination therapy (either ICIs plus CTX or ICIs plus ICIs) presented better OS compared with CTX alone. In terms of PFS, combination therapy produced a noticeable benefit over CTX. Regarding the SUCRA ranking, atezolizumab plus CTX was associated with the best ranking for OS and pembrolizumab plus CTX was the best in PFS. In terms of safety, a single ICI had better safety profile than CTX and combination therapy had a similar risk of grade 3–5 adverse events with CTX. Conclusions: Our NMA results revealed that combination therapy has better ranking compared with monotherapy in OS and acceptable AEs. ICIs alone present non-inferior OS but a lower incidence of AEs compared with CTX.

Angiosarcoma (AS) is a rare aggressive tumor originating from endothelial cells. We reported a 66-year-old female with primary renal angiosarcoma (PRA) who presented as urothelial carcinoma with hematuria and dysuria. Based on ureterorenoscopic tumor biopsy, the initial diagnosis suggested low-grade non-invasive urothelial carcinoma. However, the specimen retrieved from nephroureterectomy confirmed the diagnosis of primary renal angiosarcoma. Primary renal angiosarcoma could uncommonly present as urothelial carcinoma in renal pelvis. Surgical resection remains to be the most effective therapy but there is no consensus about adjuvant therapies. The overall prognosis of primary renal angiosarcoma is dismal., Highlights • Primary renal angiosarcoma is a rare disease that could mimic urothelial carcinoma. • Surgical resection is considered to be main treatment. The effectiveness osf adjuvant therapies remain to be clarified.

Objectives To investigate the prognostic significance of sarcopenic cachexia compared to sarcopenia without cachexia in the outcomes of upper urinary tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy (RNU). Materials and methods Between 2011 and 2016, 163 patients with UTUC who received RNU at a tertiary medical center were included. Pre-operatively clinical data, history, and abdominal computer tomography scans were analyzed retrospectively. The diagnosis of sarcopenia was based on abdominal computed tomography data on the patient’s skeletal muscles. Outcomes of relapse-free, cancer-specific, and overall survival were analyzed by multivariate Cox regression. Results After adjusting for age, sex, pre-operatively estimated glomerular filtration rate, body mass index, underlying diseases, tumor grade, and tumor stage, cachexia was a significant poor prognostic factor for relapse-free survival (hazard ratio [HR]: 18.5, 95% confidence interval [CI]: 2.87–118, p = 0.002) and cancer-specific survival (HR: 26.6, 95% CI: 4.04–175, p = 0.001). In contrast, sarcopenia without cachexia was not a significant predictor of cancer outcomes. Conclusions To date, this is the first study to investigate the effect of cachexia among sarcopenic patients with UTUC treated with RNU. We identified the prognostic significance of cachexia on outcomes. Indeed, when UTUC is treated with RNU, we should evaluate not only sarcopenia status but also cachexia. The low survival rate among patients with UTUC complicated with cachexia deserves attention.

Partial nephrectomy (PN) is the standard procedure for most patients with localized renal cancer. Laparoscopy has become the preferred surgical approach to target this cancer, but the steep learning curve with laparoscopic PN (LPN) remains a concern. In LPN intracorporeal suturing, the operation time is further extended even under robot assistance, a step which prolongs warm ischemic time. Herein, we shared our experience to reduce the warm ischemia time, which allows surgeons to perform LPN more easily by using a combination of hemostatic agents to safely control parenchymal bleeding. Between 2015 and 2018, we enrolled 52 patients who underwent LPN in our hospital. Single-site sutureless LPN and traditional suture methods were performed in 33 and 19 patients, respectively. Preoperative, intra-operative, and postoperative variables were recorded. Renal function was evaluated by estimated glomerular filtration rate (eGFR) pre- and postoperatively. The average warm ischemia time (sutureless vs. suture group, 11.8 &plusmn, 3.9 vs. 21.2 &plusmn, 7.2 min, p &lt, 0.001) and the operation time (167.9 &plusmn, 37.5 vs. 193.7 &plusmn, 42.5 min, p = 0.035) were significantly shorter in the sutureless group. In the sutureless group, only 2 patients suffered from massive urinary leakage (&gt, 200 mL/day) from the Jackson Pratt drainage tube, but the leakage spontaneously decreased within 7 days after surgery. eGFR and serum hemoglobin were not found to be significantly different pre- and postoperatively. All tumors were removed without a positive surgical margin. All patients were alive without recurrent tumors at mean postoperative follow-ups of 29.3 &plusmn, 12.2 months. Single-site sutureless LPN is a feasible surgical method for most patients with small exophytic renal cancer with excellent cosmetic results without affecting oncological results.

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.

Objective. In the present clinical trial, we evaluated the therapeutic effects of low-intensity extracorporeal shockwave therapy (LiESWT) on overactive bladder (OAB). Methods. Female subjects with ages of 20-75 years and who have been clinically diagnosed with OAB were included in the study. The LiESWT (DUOLITH SD1 T-TOP, AG) applicator was placed on the suprapubic skin area and applied with an intensity of 0.25 mJ/mm2, 3000 pulses, and 3 pulses/second. To assess the therapeutic efficacy, all subjects were required to complete the validated OAB symptoms and life bothersome questionnaires, 3-day urinary diary, uroflowmetry, and post-voided residual urine (PVR) measurement at 4 weeks of LiESWT (W4), 8 weeks of LiESWT (W8), 1-month follow-up (F1), and 3-month follow-up (F3) after LiESWT. Result. 82 subjects with the mean age of 56.5±1.2 years were enrolled. The questionnaire scores were significantly improved at W4, W8, F1, and F3 as compared to baseline data (W0). At W8, the mean values of functional bladder capacity were meaningfully increased. According to the 3-day urinary diary, daytime frequency, urgency, and nocturia were significantly decreased. The uroflowmetry results showed that the mean voided urine volume and the maximal flow rate (Qmax) were noticeably increased. PVR volume was also significantly decreased. Conclusions. The data demonstrated that 8-week LiESWT ameliorated the OAB symptoms, promoted the uroflow parameters, and improved the quality of life (QoL) in OAB patients, suggesting that LiESWT might serve as an alternative noninvasive therapy for OAB.

Abiraterone and enzalutamide may increase the risk of cardiovascular events in patients with castration-resistant prostate cancer (CRPC). A comprehensive literature search was performed using a combination of keywords related to “abiraterone,” “enzalutamide,” “prostate cancer,” and “adverse events.” Phase II–IV randomized controlled trials (RCTs) on abiraterone or enzalutamide for patients with nonmetastatic or metastatic CRPC were included. Outcome measures included (1) any grade cardiac disorder, (2) severe grade cardiac disorder, (3) any grade hypertension, and (4) severe grade hypertension, as defined by the Common Terminology Criteria for Adverse Events. Pairwise meta-analysis and Bayesian network meta-analyses were performed to investigate the risk ratios (RRs) of abiraterone and enzalutamide. Surface under cumulative ranking curves (SUCRAs) and cumulative ranking probability plots based on the probability of developing cardiac disorders or hypertension were presented. A total of 7103 patients from seven RCTs were included. Upon pairwise meta-analysis, abiraterone was associated with increased risks of any grade (RR = 1.34, 95% confidence interval (CI) = 1.05–1.73) and severe grade cardiac disorders (RR = 1.71, 95% CI = 1.16–2.53); enzalutamide was associated with increased risks of any grade (RR = 2.66, 95% CI = 1.93–3.66) and severe grade hypertension (RR = 2.79, 95% CI = 1.86–4.18). Based on the SUCRA rankings, abiraterone had a higher probability of cardiac disorders (84.84% for any grade and 85.12% for severe grade) than enzalutamide (62.83% for any grade and 50.76% for severe grade); whereas enzalutamide had a higher probability of hypertension (99.43% for any grade and 89.71% for severe grade) than abiraterone (49.08% for any grade and 49.37% for severe grade). Abiraterone and enzalutamide had different adverse effects on the cardiovascular system. We should take this into consideration when we are deciding on the choice of novel hormonal agents for patients with CRPC.

This study aimed to evaluate the therapeutic effects of Low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence (SUI). The investigation was a single-arm, open-label, multicentre study conducted in Taiwan. 50 female patients with SUI received LiESWT-treated with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/second, once weekly for 4-weeks (W4) and 8-weeks (W8). The pad test, uroflowmetry, life quality questionnaires, and 3-day urinary diary measurement were performed before and after LiESWT intervention. The results revealed that 8-week of LiESWT treatment meaningfully improved urine leakage (pad test), maximum flow rate, post-voided residual urine, average urine volume, functional bladder capacity, urinary frequency, urgency symptom, and nocturia, which also persisted to show significant improvements at 1-month follow up (F1). Moreover, bothersome questionnaires scores were significantly improved at W4, W8, and F1 as compared to the baseline (W0). These results indicated that 8 weeks of LiESWT attenuated SUI symptoms on physical activity, reduced bladder leaks and overactive bladder (OAB), implying that LiESWT brought significant improvement in the quality of life. (ClinicalTrials.gov number, NCT04059133).

The traditional transurethral resection of the prostate (TURP) is considered as gold-standard surgical treatment to relieve symptoms resulting from bladder outlet obstruction by prostate enlargement. However, with the advances of novel laser technologies and more experienced surgeon conquering the steep learning curve, anatomical endoscopic enucleation of prostate (AEEP) has become a more popular alternative surgical technique. Although AEEP has compatible functional outcome, less blood loss, shorter catheterisation duration and hospital stay, the risk of post-operative urinary incontinence (UI) is often an issue of concern. In this review, we focus on discussion about risk factors related to increased incidence of UI, some surgical tips to avoid damaging external urinary sphincter and treatment strategies to facilitate recovery of urinary continence after surgery.

To assess whether our novel uterus-sparing procedure- laparoscopic organopexy with non-mesh genital(LONG) suspension is an effective, safe, and timesaving surgery for the treatment of apical prolapse. Forty consecutive women with main uterine prolapse stage II or greater defined by the POP quantification(POP-Q) staging system were referred for LONG procedures at our hospitals. Clinical evaluations before and 6 months after surgery included pelvic examination, urodynamic study, and a personal interview to evaluate urinary and sexual symptoms with overactive bladder symptom score(OABSS), the short forms of Urogenital Distress Inventory(UDI-6) and Incontinence Impact Questionnaire(IIQ-7), and the Female Sexual Function Index(FSFI). After follow-up time of 12 to 30 months, anatomical cure rate was 85%(34/40), and the success rates for apical, anterior, and posterior vaginal prolapse were 95%(38/40), 85%(34/40), and 97.5%(39/40), respectively. Six recurrences of anterior vaginal wall all suffered from significant cystocele (stage3; Ba>+1) preoperatively. The average operative time was 73.1 ± 30.8 minutes. One bladder injury occurred and was recognized during surgery. The dyspareunia domain and total FSFI scores of the twelve sexually-active premenopausal women improved postoperatively in a significant manner (P

Objectives: Although antimuscarinic drugs are considered the gold standard for overactive bladder (OAB), high discontinuation rates have been observed. However, no information is known about this in Taiwan. We investigated the persistence and switch rates among different antimuscarinics prescribed for OAB and evaluated whether different comorbidities impacted the persistence with prescribed antimuscarinics in Taiwan. Materials and Methods: We obtained retrospective claims from a Taiwanese health insurance database for patients with OAB; any first claim for the target drugs (tolterodine extended release [ER], tolterodine immediate release [IR], oxybutynin ER, oxybutynin IR, solifenacin, propiverine, and flavoxate) between January 2004 and December 2013 was included. The prescription claims were tracked for 1 year to calculate the time of persistence and switch rates. Comorbidities, including hypertension, diabetes mellitus, and hyperlipidemia, were recorded. Significant factors for discontinuation were investigated by using a Cox proportional hazards model. Results: A total of 24,381 patients with OAB were prescribed the target antimuscarinics. The most prescribed drug during the 10-year period was flavoxate (8339 patients). Of the 3481 patients with chronic OAB, the drug with the longest mean persistence was solifenacin (125 days). At 12 months, the persistence rate varied from 7.6% for oxybutynin ER to 4.3% for propiverine. The switch rates varied from 40.3% for propiverine to 25.7% for solifenacin. The Cox proportional hazards model showed that hyperlipidemia was the only comorbidity significantly associated with discontinuation (hazards ratio: 1.12, 95% confidence interval: 1.03–1.21, P = 0.006). Conclusions: In this large nationwide Taiwanese study, 12-month persistence was generally low for all antimuscarinics. Solifenacin was associated with the longest mean persistence and the lowest switch rates, oxybutynin ER had the highest 12-month persistence rate, and hyperlipidemia was significantly associated with lower persistence.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague–Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks’ LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Objective The toxicity of ketamine to the genitourinary system not only involves the lower urinary tract but also the upper urinary tracts. Reports showed that ketamine abuse may cause hydronephrosis and renal function deterioration. However, the exact pathophysiological mechanism of renal injury has not been investigated. The aim of the present study is to investigate the renal injury after ketamine addition in an animal model. Materials and methods Thirty Sprague–Dawley rats were divided into three groups: control group, K-14D group, and K-28D group. The K-14D and K-28D groups received ketamine (25 mg/kg/d, intraperitoneally) through daily injections for a period of 14 days and 28 days, respectively. Masson's trichrome stains were carried out to show the histological changes. Western blotting and reverse transcription polymerase chain reaction were carried out to examine the expressions of profibrosis markers and fibrosis-associated proteins. Results Masson's trichrome stain showed that no significant renal hydronephrosis occurred after ketamine treatment. However, ketamine treatment increased the fibrosis of the tubule-interstitium and increased collagen deposition and fibronectin expression. These alterations were accompanied by increases in the expression of inflammatory and fibrosis markers, fibronectin, and type I collagen after ketamine treatment. The profibrosis marker, transforming growth factor-β (TGF-β), increased significantly after 14 days and 28 days of ketamine treatment both in terms of mRNA and protein levels. Conclusion Ketamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.

Ketamine-induced ulcerative cystitis (KIC) initially damaged the bladder mucosa and induced contracted bladder thereafter. Hyaluronan (hyaluronic acid; HA) instillation to the bladder has been used to treat KIC. The present study investigated bladder injury by urothelial defect and HA degeneration and bladder repair by urothelium proliferation and differentiation. This work was based on the hypothesis that HA treatment altered the bladder urothelial layer and the expression of hyaluronan-metabolizing enzymes and/or HA receptors in KIC. Cystometrogram study and tracing analysis of voiding behavior revealed that the ketamine-treated rats exhibited significant bladder hyperactivity with an increase in micturition frequency and a decrease in bladder capacity. The expression of inflammatory and fibrosis markers was also increased in the ketamine-treated group. Moreover, ketamine administration decreased the expression of urothelial barrier-associated protein, altered HA production, and induced abnormal urothelial differentiation, which might attribute to urothelial lining defects. However, HA instillation ameliorated bladder hyperactivity, lessened bladder mucosa damage, and decreased interstitial fibrosis. HA instillation also improved the level of HA receptors (CD44, Toll-like receptor-4, and receptor for HA-mediated motility) and HA synthases 1 to 3 and decreased the expression of hyaluronidases in the urothelial layer of bladder, resulting in enhanced mucosal regeneration. These findings suggested that HA could modulate inflammatory responses, enhance mucosal regeneration, and improve urothelial lining defects in KIC.

Objective Nephroureterectomy with bladder cuff excision is the current gold standard for the treatment of upper-tract urothelial carcinoma (UTUC). Currently, routine follow-up cystogram is performed prior to Foley catheter removal to evaluate the bladder cuff excision wound. The aim of this study was to investigate the role of the postoperative cystogram in the bladder cuff excision procedure. Materials and methods This was a retrospective study of 193 patients diagnosed with UTUC post nephroureterectomy and bladder cuff excision between January, 2010, and January, 2016. Patient demographics, performance of cystogram, types of bladder cuff excision, and postoperative outcomes were recorded. Patients were classified into two groups depending on whether or not routine postoperative cystogram was performed. Results A total of 125 patients were included in this study and, of these, 102 patients underwent routine cystogram on Postoperative Day 7 (Group 1), while 23 patients underwent Foley catheter removal on Postoperative Day 7 without any imaging studies (Group 2). Univariate analysis showed no differences in age, sex, comorbidities, surgical approach, or stage of the primary tumor. No patient from either group had urinoma, pelvic abscesses, and tumor growth from bladder cuff wound was not observed in any patient within the 1-year postoperative follow-up period. Both groups of patients had a similar rate of postoperative urinary tract infections with sepsis ( p = 0.639), time to Foley catheter removal ( p = 0.630), time to drainage tube removal ( p = 0.264), and length of hospitalization ( p = 0.373). Conclusion Foley catheter removal on Postoperative Day 7 after nephroureterectomy with bladder cuff excision without routine cystogram appears to be safe in the majority of the UTUC patients. A large, multi-institutional study is required before this method can be recommended for widespread clinical practice.

Background Repeated evidence from animal models suggests a strong link between vascular endothelial growth factor (VGEF) and penile vasculature and erectile function because VEGF can alter the physiologic pathways involved in the regulation of penile vasomotor tone. Aim To investigate three VEGF polymorphisms and their link to erectile dysfunction (ED). Methods We enrolled 688 Taiwanese men with a mean age of 55.6 years (SD = 4.5) during a free health screening. All participants provided complete medical histories and underwent physical examinations. Fasting blood samples were obtained for biochemical analysis and hormone profiling. The allelic discrimination of three VEGF gene polymorphisms (460T/C [rs833061], 1154G/A [rs1570360], and 2578A/C [rs699947]) was performed using validated TaqMan single-nucleotide polymorphism genotyping assays. Outcomes Subjects underwent assessment using the simplified five-item International Index of Erectile Function to diagnose and assess ED severity. Results The results showed that diabetes mellitus (odds ratio [OR] = 3.27, P < .01), hypertension (OR = 3.47, P < .01), and having the VEGF 2578A allele (OR = 1.54, P = .01) were the three most independent risk factors for ED. In univariate analysis, all three VEGF polymorphisms (460C, 1154A, and 2578A) were significantly associated with a higher prevalence of coronary artery disease (P < .01) and greater frequencies of hypertension were found in carriers of the 1154A allele and the 2578A allele (P = .01). Multiple logistic regression analysis showed a significant association between VEGF 2578A allele carrier status and ED (OR = 1.54, 95% CI = 1.10∼2.15, P = .01). Furthermore, the prevalence and severity of ED were significantly increased with an increment of the 2578A allele number (P < .05). Clinical Implications VEGF 2578C/A gene polymorphisms could be a genetic susceptibility factor for the development of ED. Strength and Limitation This is the first study to investigate the genetic susceptibility of VEGF polymorphisms to ED. This study was cross-sectional with a lack of functional and molecular production investigations. Data on the association among conditions might not allow definitive conclusions about causal links. Conclusion This study showed that VEGF 2578A allele carriers in a Taiwanese population are at greater risk for ED.

Acromegaly is a rare disease associated with an increased risk of prostate enlargement. Severe prostate enlargement with severe lower urinary tract symptoms (LUTS) in an acromegalic patient is even more uncommon. Herein we report on a 55-year-old man who was diagnosed with acromegaly and prostate enlargement at 40 years of age. Transsphenoidal surgery, postoperative radiotherapy, and octreotide medical therapy failed to control the acromegaly, and growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels remained elevated. When the patient was 53 years of age, severe LUTS and prostate enlargement (prostate volume = 128 mL) were noted. However, LUTS improved and prostate volume decreased markedly after 5α-reductase inhibitors were used, despite the poorly controlled acromegaly (elevated GH and IGF-1 levels). This is the first long-term observation of LUTS and prostate enlargement in a poorly controlled acromegalic patient. Although the GH-IGF-1 axis was a factor contributing to prostate enlargement, the present case suggests that androgens may still play an essential role in prostate enlargement and symptoms in active acromegalic patients >50 years of age. Indeed, we should be aware that suppressing the GH-IGF-1 axis is not the only treatment choice for prostate enlargement in acromegalic patients, and even in poorly controlled acromegalic patients in whom suppression of the GH-IGF-1 axis is difficult. Symptomatic prostate enlargement in cases of active acromegaly can be treated with 5α-reductase inhibitors, as in general benign prostate hyperplasia populations.

Uphold transvaginal mesh implantation is an option for treating pelvic organ prolapse (POP). This prospective cohort study aims to evaluate the effect of Uphold transvaginal mesh implantation on female sexual function. 205 women with symptomatic POP were recruited and evaluated pre-operatively and re- evaluated six months post-operatively in terms of anatomical restoration, quality of life influenced by urinary incontinence and female sexual function. 30 women eventually completed the assessments and been statistically evaluated. The main outcome focused on sexual function. In our study, we found that Uphold transvaginal mesh surgery could achieve effective anatomical restoration of POP and better sexual function regardless of concomitant sling surgery.

Urolithiasis and osteoporosis are two different pathological entities, but are both important public health issues in older patients. Moreover, the two diseases may share some similar pathogenesis pathway. Currently, few studies focus on the relationship between urolithiasis and osteoporosis. Furthermore, whether the common mobilities influence the long-term osteoporosis rate in urolithiasis patients has never been studied. In the present study, we used the Taiwan National Health Insurance Database (LHID 2000) compiled by the NHI from 1996 to 2013 to determine whether urolithiasis influenced long-term osteoporosis; controls were matched for age, sex, and other comorbidities (including hypertension, diabetes mellitus, dyslipidemia, liver disease, and cardiovascular disease). We included a total of 91,254 patients, including 22,575 patients with urolithiasis and 68,679 control patients. There was a significant difference between the incidence of osteoporosis between the urolithiasis and control groups (adjusted hazard ratio 1.34, 95% CI 1.19–1.79, p

Simple Summary Overactive bladder (OAB) is a common urologic condition with urinary frequency, urinary urgency, nocturia, and urgency incontinence, which can get in the way of a patient’s social life, exercise, work, and sleep. Exploring a promising option for OAB patients is very important, especially one with less side effects or invasive alternations. This study uses low intensity extracorporeal shock wave therapy (LiESWT) to investigate the therapeutic effect and duration on OAB symptoms. Abstract Background: The present study attempted to investigate the therapeutic effect and duration of low intensity extracorporeal shock wave therapy (LiESWT) on overactive bladder (OAB) symptoms, including social activity and the quality of life (QoL). Methods: In this prospective, randomized, single-blinded clinical trial, 65 participants with OAB symptom were randomly divided into receive LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) once a week for 8 weeks, or an identical sham LiESWT treatment without the energy transmission. We analyzed the difference in overactive bladder symptom score (OABSS) and 3-day urinary diary as the primary end. The secondary endpoint consisted of the change in uroflowmetry, post-voided residual (PVR) urine, and validated standardized questionnaires at the baseline (W0), 4-week (W4) and 8-week (W8) of LiESWT, and 1-month (F1), 3-month (F3) and 6-month (F6) follow-up after LiESWT. Results: 8-week LiESWT could significantly decrease urinary frequency, nocturia, urgency, and PVR volume, but meaningfully increase functional bladder capacity, average voided volume and maximal flow rate (Qmax) as compared with the W0 in the LiESWT group. In addition, the scores calculated from questionnaires were meaningfully reduced at W4, W8, F1, F3, and F6 in the LiESWT group. Conclusions: Our results revealed that the therapeutic efficacy of LiESWT could improve voided volume and ameliorate OAB symptoms, such as urgency, frequency, nocturia, and urinary incontinence, and lasted up to 6 month of follow-up. Moreover, LiESWT treatment brought statistically significant and clinically meaningful improvements in social activity and QoL of patients. These findings suggested that LiESWT could serve as an alternative non-invasive therapy for OAB patients.

Simple Summary Long-term ketamine abuse may increase urinary frequency, nocturia, urgency, bladder pain, dysuria, and sometimes hematuria. Evaluation of the pathophysiological mechanism of bladder voiding dysfunction in ketamine-induced cystitis (KIC) patients is a critical step for therapy. This study uses autophagy inducer (rapamycin, mTOR inhibitor) and inhibitor (wortmannin, PI3K-III inhibitor) to identify the role of autophagy in bladder angiogenesis alteration and bladder hyperactivity improvement. Abstract The present study attempts to elucidate whether autophagy alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity—thereby influencing bladder function in ketamine-induced cystitis (KIC). In our methodology, female Sprague-Dawley (S-D) rats were randomly divided into the control group, the ketamine group, the ketamine+rapamycin group, and the ketamine+wortmannin group. The bladder function, contractile activity of detrusor smooth muscle, distribution of autophagosome and autolysosome, total white blood cells (WBCs) and leukocyte differential counts, the expressions of autophagy-associated protein, angiogenesis markers, and signaling pathway molecules involved in KIC were tested, respectively. The data revealed that treatment with ketamine significantly results in bladder overactivity, enhanced interstitial fibrosis, impaired endothelium, induced eosinophil-mediated inflammation, swelling, and degraded mitochondria and organelles, inhibited angiogenesis, and elevated the phosphorylation of Akt. However, treatment with rapamycin caused an inhibitory effect on vascular formation, removed ketamine metabolites, decreased the eosinophil-mediated inflammation, and ameliorated bladder hyperactivity, leading to improve bladder function in KIC. Moreover, wortmannin treatment reduced basophil-mediated inflammatory response, improved bladder angiogenesis by increasing capillary density and VEGF expression, to reverse antiangiogenic effect to repair KIC. In conclusion, these findings suggested that autophagy could modulate inflammatory responses and angiogenesis, which improved bladder function in KIC.

Objectives: Urinary incontinence (UI) is more prevalent in the elderly populations with dementia than without dementia, and Alzheimer’s disease (AD) is the most common cause of dementia. Urinary incontinence may complicate AD morbidity and mortality. Therefore, this study aimed to evaluate the prevalence and annual incidence and determine the risk possibility of UI, which is the main type of incontinence in patients with AD in Taiwan. Methods: A total of 933 patients with AD were included in the study cohort, and a total of 2799 patients without AD by 1:3 proportion compared to the study cohort were used as a matched cohort. All participants were selected from the National Health Insurance Research Database in 2000 sample population. We utilize Cox proportional hazard regression to evaluate the risk of UI and cumulative incidence ratio curve to analyze the cumulative incidence function. Prevalence and annual incidence rate are calculated in individual medication including rivastigmine, donepezil, galantamine, and memantine only being initiated in patients with AD. Results: The risk of UI is higher in AD cohort (hazard ratio: 1.54, 95% confidence interval: 1.13-2.09). The cumulative incidence ratio of UI event between AD cohort and matched cohort presents statistical significance ( P < .001). Annual incidence and prevalence of UI in patients with AD are 6.2% and 4.2%, respectively. Conclusion: The present results suggest that the risk of UI is higher in patients with AD than in the general population.

Metabolic syndrome (MtS) and kidney stone are two common aging diseases with male dominant. This is the first study regarding the potential impact of MtS and its components on kidney stone in aging Chinese population.A total of 694 males with a mean age of 55.6 years were enrolled. The definition of MtS was according to the modified criteria developed by the Bureau of Health Promotion in Taiwan. Subjects were classified as having a disease of kidney stones according to diagnosis by a physician with available medical records or evidence from ultrasonography judged by an investigator of urologist.Using age-adjusted multivariate logistic regression analysis, our results showed that subjects with kidney stone had significantly higher prevalence of MtS (p = 0.04, OR = 1.74, 95% CI: 1.0 1-3.00). The presence of MtS had significant correlation with kidney stone (p = 0.01, OR = 1.83, 95% CI: 1.1 4-2.93), which were associated with the increment of MtS components (p 0.01). After adjusting for age and testosterone level, abnormal blood pressure (BP) was the most significantly independent component of MtS for kidney stone among the MtS components (p 0.01, OR = 2.81, 95% CI: 1.46-5.39).In aging Taiwanese males, the presence of MtS and its components are strongly associated with kidney stone. Abnormal BP is the most significant risk component of MtS for kidney stone.

It has been suggested that herpes zoster may increase the risk of subsequent prostate cancer (PCa). We aimed to assess the risk of PCa following herpes zoster by the population-based follow-up study. This is a retrospective study and data are from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised all patients with a diagnosis of herpes zoster (International Classification of Diseases, 9th Revision, Clinical Modification code 053.0–053.9) and followed for PCa from 1997 to 2013 (n = 11,376). Subjects younger than 20 years of age were excluded. The match-control cohort was identified from the Registry of Beneficiaries of the NHIRD and randomly selected by matching with the study cohort at a 3:1 ratio based on age (every 5-year span), and year of herpes zoster diagnosis (n = 34,128). We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) for subsequent PCa, after controlling for potential cormobidities. Men with and without herpes zoster had similar age and comorbidity distributions. Among the 45,504 sampled patients, 1011 (2.22%) developed PCa during the 10 years of follow-up, 276 (2.43%) from the study cohort and 735 (2.15%) from the match-control cohort and the incidence rate was 3.13 and 2.72 per 1000 person years respectively. Patients with herpes zoster were more likely to develop PCa than patients in the match-control cohort (HR = 1.15; 95% confidence interval (CI) = 1.00–1.32, P value = .045). After adjusting for age and comorbidities, herpes zoster was associated with a 1.15 increased risk of PCa (adjusted HR = 1.15, 95% CI = 0.99–1.32, P value = .054). Our study indicates that preceding herpes zoster infection is a suggestive risk marker for subsequent PCa after controlling for potential confounders. Further prospective studies are needed to determine the relationship between herpes zoster and PCa.

Introduction & objectivesIt has been suggested that lower urinary tract symptoms-benign prostatic hyperplasia (LUTS-BPH) may be a risk factor for inguinal hernia (IH). The aim of this study was to examine the emergence of a subsequent IH diagnosis in men with and without LUTS-BPH.MethodsFrom a database derived from the National Health Insurance Program covering 99% of the population in Taiwan, 22,310 men with LUTS-BPH and 22,310 matched men without LUTS-BPH were identified and followed for IH from 1997 to 2013. Both IH and LUTS-BPH were defined by the ninth revision of the International Classification of Diseases code (ICD9). Subjects younger than 20 years of age and with IH diagnosed before the index date were excluded. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for subsequent IH, controlling for potential confounders.ResultsMen with and without LUTS-BPH had similar age and comorbidity distributions. During the 10 years of follow-up, 1,303 (5.84%) men with LUTS-BPH and 735 (2.53%) men without LUTS-BPH developed IH. The mean time to IH was 4.02 years and 4.44 years, respectively. After adjusting for age and comorbidities, LUTS-BPH was associated with a two-fold increased risk of IH (HR:2.25, 95% CI = 2.04-2.49).ConclusionThis nation-wide population-based cohort study showed that LUTS-BPH increased the risk of subsequent IH in a Taiwanese Population.

To present a comprehensive evaluation of anterior/apical and/or posterior prolapse repair systems with a focus on safety and surgical efficacy.Two hundred and twenty women with pelvic organ prolapse (POP) stage II-IV were referred for single-incision transvaginal mesh procedures in a single institution. Pre- and postoperative assessments included pelvic examination, urodynamic studies, and personal interviews about patients' quality of life and urinary symptoms.The anatomical success rate was 92.3 % (203/220), regardless of primary or de-novo POP, at 12-38 month follow-up. The POP quantification parameters, except total vaginal length, improved significantly after surgery (p0.05). Complications included bladder injury (one case), mesh exposure (six cases) and urinary retention that required intermittent catheterization (five cases). There were no cases of bowel injury during surgery. The results indicated that 29 % of patients had de-novo stress urinary incontinence and 7.7 % of patients had de-novo POP after surgery.The apical vaginal suspension system is a safe and effective procedure, creating good anatomical restoration and significant improvement in quality of life. However, the rate of de-novo POP in the anterior compartment of the vagina (31.8 %) seems high after treatment with apical and posterior prolapse repair systems.

Hysterectomy is the empirical treatment for female pelvic organ prolapse (POP) without robust evidence to prove its efficacy. Uphold transvaginal mesh (TVM) system is an innovated device with smaller area, superior anterior/apical support with single incision to treat POP. The prospective cohort study aims to evaluate Uphold TVM’s performance with or without concomitant hysterectomy. Inclusion criteria specify patients suffering from stage 2 or more anterior/apical prolapse without previous hysterectomy. Exclusion criteria specify those with contraindications to uterine preservation, such as leiomyomas, adenomyosis, endometrial hyperplasia, abnormal uterine bleeding, postmenopausal bleeding, cervical dysplasia, receiving tamoxifen treatment, family history of gynecology cancer, or colon cancer and incapability to be routinely followed. Thirty patients are recruited in the hysterectomy group and 66 patients in the hysteropexy group. The results demonstrate that patients with Uphold mesh only experience longer vaginal length, shorter operation duration, less blood loss and less post-operation pain. The performance in anatomical correction, lower urinary tract symptoms improvement, de novo dyspareunia, urodynamic study parameters and mesh extrusion rates are comparable with or without uterus preservation. The information is useful in pre-operation counseling, when the patient can make an educated choice whether or not to receive concomitant hysterectomy.

Valproate (VPA) is a well-known drug for treating epilepsy and mania, but its action in neuropathic pain is unclear. We used a chronic constriction injury (CCI) model to explore whether VPA prevents neuropathic pain-mediated inflammation and neuronal death. Rats were treated with or without VPA. CCI + VPA rats were intraperitoneally injected with VPA (300 mg/kg/day) from postoperative day (POD) 1 to 14. We measured paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) 1 day before surgery and 1, 3, 7, 14 days after CCI and harvested the sciatic nerves (SN), spinal cord (SC) and dorsal root ganglia (DRG) on POD 3, 7, and 14. PWL and PWT were reduced in CCI rats, but increased in CCI + VPA rats on POD 7 and POD 14. VPA lowered CCI-induced inflammatory proteins (pNFκB, iNOS and COX-2), pro-apoptotic proteins (pAKT/AKT and pGSK-3β/GSK-3β), proinflammatory cytokines (TNF-α and IL-1β) and nuclear pNFκB activation in the SN, DRG and SC in CCI rats. COX-2 and pGSK-3 proteins were decreased by VPA on immunofluorescence analysis. VPA attenuated CCI-induced thermal and mechanical pain behaviors in rats in correlation with anti-neuroinflammation action involving reduction of pNFκB/iNOS/COX-2 activation and inhibition of pAKT/pGSK-3β-mediated neuronal death from injury to peripheral nerves.

Metabolic syndrome (MetS) and ovarian hormone deficiency could affect bladder storage dysfunction. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound in green tea, has been shown to protect against ovarian hormone deficiency induced overactive bladder (OAB). The present study investigated oxidative stress induced by MetS and bilateral ovariectomy (OVX), and elucidated the mechanism underlying the protective effect of EGCG (10 umol/kg/day) on bladder overactivity. Rats were fed with high fat high sugar (HFHS) diet to induce MetS and received ovariectomy surgery to deprive ovarian hormone. By dieting with HFHS for 6 months, rats developed MetS and OAB. MetS + OVX deteriorated bladder storage dysfunction more profound than MetS alone. MetS and MetS + OVX rats showed over-expression of inflammatory and fibrosis markers (1.7~3.8-fold of control). EGCG pretreatment alleviated storage dysfunction, and protected the bladders from MetS and OVX - induced interstitial fibrosis changes. Moreover, OVX exacerbated MetS related bladder apoptosis (2.3~4.5-fold of control; 1.8~2.6-fold of Mets group), enhances oxidative stress markers (3.6~4.3-fold of control; 1.8~2.2-fold of Mets group) and mitochondrial enzyme complexes subunits (1.8~3.7-fold of control; 1.5~3.4-fold of Mets group). EGCG pretreatment alleviated bladder apoptosis, attenuated oxidative stress, and reduced the mitochondrial and endoplasmic reticulum apoptotic signals. In conclusions, HFHS feeding and ovarian hormone deficiency enhances the generation of oxidative stress mediated through mitochondrial pathway. EGCG reduced the generation of oxidative stress and lessened bladder overactivity.

Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories) is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT) was recently reported to be able to improve pain, urinary symptoms, and even sexual function by inducing neovascularization and anti-inflammation, reducing muscle tone, and influencing nerve impulses. This study evaluates whether combined treatment with LI-ESWT can restore clinical ability and quality of life (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm prospective study. Patients with CPPS without more than a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH-CPSI, visual analog scale (VAS) score, International Prostate Symptom Score (IPSS), and the five-item version of the International Index of Erectile Function (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT. Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist circumference was the only significant predictor of a successful response to LI-ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to traditional 3-As therapy. Further studies are needed to determine an adequate therapeutic protocol and important predictors in patients with different CPPS etiologies.

A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ∼5,800 somatic mutations to ∼13,500 gene expression levels (in total, ∼78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses. We further prioritized 394 biologically risky mutational candidates which mapped to 275 gene loci and demonstrated that these genes collaborated with expression features were significantly enriched in targets of drugs approved for solid tumors, suggesting the plausibility of drug repurposing. Taken together, we integrated a fundamental endometrial cancer genomic profile into clinical circumstances, further shedding light for clinical implementation of genomic-based therapies and guidance for drug discovery.

Objective To investigate the protective effect of green tea epigallocatechin gallate (EGCG) on long-term ketamine-induced ulcerative cystitis (KIC) using a ketamine addiction rat model. Materials and methods Thirty Sprague-Dawley rats were divided into three groups which received saline, ketamine (25 mg/kg/d), or ketamine combined with EGCG (10 μM/kg) for a period of 28 days. In each group, cystometry and a metabolic cage micturition pattern study were performed weekly. Masson's trichrome study was done to evaluate the morphologic changes. Western blot analyses were carried out to examine the expressions of inflammatory protein [transforming growth factor-β (TGF-β)] and fibrosis proteins (fibronectin and type I collagen) in bladder tissues. Results Chronic ketamine treatment resulted in bladder hyperactivity with a significant increase in micturition frequency and a decrease in bladder compliance. These alterations in micturition pattern were accompanied by increases in the expressions of inflammatory and fibrosis markers, TGF-β, fibronectin, and type I collagen after long-term ketamine treatment. Masson's trichrome stain showed that ketamine treatment decreased urothelium thickness while increasing the collagen to smooth muscle ratio and exacerbating interstitial fibrosis. By contrast, simultaneous EGCG and ketamine treatment reversed ketamine-induced damage to almost control levels, showing the protective effect of EGCG. Conclusion This protective effect of EGCG may come from its antiinflammatory and antifibrotic properties.