Efficacy and Safety of Low-Dose Intravesical OnabotulinumtoxinA Injections in Female Patients With Detrusor Overactivity With Detrusor Underactivity.

PURPOSE: We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). METHODS: This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. RESULTS: Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. CONCLUSION: Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.

A Streamlined PENK Methylation Test in Urine DNA, EarlyTect BCD, Effectively Detects Bladder Cancer in Patients with Hematuria.

The current noninvasive diagnostic approaches for detecting bladder cancer (BC) often exhibit limited clinical performance, especially for the initial diagnosis. This study aims to evaluate the validity of a streamlined urine-based PENK methylation test called EarlyTect BCD in detecting BC in patients with hematuria scheduled for cystoscopy in Korean and American populations. The test seamlessly integrates two steps, linear target enrichment and quantitative methylation-specific PCR within a single closed tube. The detection limitation of the test was approximately two genome copies of methylated PENK per milliliter of urine. In the retrospective training set (n = 105), an optimal cutoff value was determined to distinguish BC from non-BC, resulting in a sensitivity of 87.3% and a specificity of 95.2%. In the prospective validation set (n = 210, 122 Korean and 88 American patients), the overall sensitivity for detecting all stages of BC was 81.0%, with a specificity of 91.5% and an area under the curve value of 0.889. There was no significant difference between the two groups. The test achieved a sensitivity of 100% in detecting high-grade Ta and higher stages of BC. The negative predictive value of the test was 97.7%, and the positive predictive value was 51.5%. The findings of this study demonstrate that EarlyTect BCD is a highly effective noninvasive diagnostic tool for identifying BC among patients with hematuria.

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder.

PURPOSE: Vibegron, a novel, potent ß3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. METHODS: A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. RESULTS: Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients' quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. CONCLUSION: Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

A Novel Incisionless Disposable Vaginal Device for Female Stress Urinary Incontinence: Efficacy and Quality of Life.

PURPOSE: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. METHODS: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. RESULTS: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. CONCLUSION: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration: The study was registered as a clinical trial (KCT0008369).

Evaluation of Sensitive Urine DNA-Based PENK Methylation Test for Detecting Bladder Cancer in Patients with Hematuria.

Hematuria is a prevalent symptom associated with bladder cancer (BC). However, the invasiveness and cost of cystoscopy, the current gold standard for BC diagnosis in patients with hematuria, necessitate the development of a sensitive and accurate noninvasive test. This study introduces and validates a highly sensitive urine-based DNA methylation test. The test improves sensitivity in detecting PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR. In a case-control study comprising 175 patients with BC and 143 patients without BC with hematuria, the test's optimal cutoff value was determined by distinguishing between two groups, achieved an overall sensitivity of 86.9% and a specificity of 91.6%, with an area under the curve of 0.892. A prospective validation clinical study involving 366 patients with hematuria scheduled for cystoscopy assessed the test's performance. The test demonstrated an overall sensitivity of 84.2% in detecting 38 cases of BC, a specificity of 95.7%, and an area under the curve of 0.900. Notably, the sensitivity for detecting Ta high grade and higher stages of BC reached 92.3%. The test's negative predictive value was 98.2%, and the positive predictive value was 68.7%. These findings highlight the potential of the PENK methylation in urine DNA using linear target enrichment followed by quantitative methylation-specific PCR test in urine as a promising molecular diagnostic tool for detecting primary BC in patients with hematuria, which may reduce the need for cystoscopy.

Identification and validation of methylated PENK gene for early detection of bladder cancer using urine DNA.

BACKGROUND: Early detection of bladder cancer (BCa) offers patients a favorable outcome and avoids the need for cystectomy. Development of an accurate and sensitive noninvasive BCa diagnostic test is imperative. DNA methylation is an early epigenetic event in the development of BCa. Certain specific aberrant methylations could serve as useful biomarkers. The aim of this study was to identify methylation biomarkers for early detection of BCa. METHODS: CpG methylation microarray analysis was conducted on primary tumors with varying stages (T1-T4) and paired nontumor tissues from nine BCa patients. Bisulfite-pyrosequencing was performed to confirm the methylation status of candidate genes in tissues and urine sediments (n = 51). Among them, PENK was selected as a potential candidate and validated using an independent set of 169 urine sediments (55 BCa, 25 benign urologic diseases, 8 other urologic cancers, and 81 healthy controls) with a quantitative methylation-specific real time PCR (mePENK-qMSP). All statistical analyses were performed using MedCalc software version 9.3.2.0. RESULTS: CpG methylation microarray analysis and stepwise validation by bisulfite-pyrosequencing for tissues and urine sediments supported aberrant methylation sites of the PENK gene as potential biomarkers for early detection of BCa. Clinical validation of the mePENK-qMSP test using urine sediment-DNA showed a sensitivity of 86.5% (95% CI: 71.2 - 95.5%), a specificity of 92.5% (95% CI: 85.7 - 96.7%), and an area under ROC of 0.920 (95% CI: 0.863 - 0.959) in detecting Ta high-grade and advanced tumor stages (T1-T4) of BCa patients. Sensitivities for Ta low-grade, Ta high-grade, T1 and T2-T4 were 55.6, 83.3, 88.5, and 100%, respectively. Methylation status of PENK was not correlated with sex, age or stage, while it was associated with the tumor grade of BCa. CONCLUSIONS: In this study, we analyzed the comprehensive patterns of DNA methylation identified that PENK methylation possesses a high potential as a biomarker for urine-based early detection of BCa. Validation of PENK methylation confirms that it could significantly improve the noninvasive detection of BCa.

Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia.

Castration-resistant prostate cancer (CRPC) is still a major concern in men's health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC.

Combination therapy with tamsulosin and traditional herbal medicine for lower urinary tract symptoms due to benign prostatic hyperplasia: A double-blinded, randomized, pilot clinical trial.

OBJECTIVES: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.

Sophisticated regulation of micturition: review of basic neurourology.

The neurological regulation of the lower urinary tract can be viewed separately from the perspective of sensory neurons and motor neurons. First, in the receptors of the bladder and urethra of sensory nerves, sensations are transmitted through the periaqueductal gray matter of the midbrain to the cerebral cortex, and the cerebrum goes through the process of decision-making. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs). UMNs coordinate storage and micturition in the brain stem so that synergic voiding can occur. LMNs facilitate muscle contractions in the spinal cord. The muscles involved in urinary storage and micturition are innervated by the somatic branches of sympathetic, parasympathetic, and peripheral nerves. Sympathetic nerves are responsible for contractions of urethral smooth muscles, while parasympathetic nerves originate from S2-S4 and are in charge of contractions of the bladder muscle. Somatic nerves originate from the motor neurons in Onuf's nucleus, which is a specific part of somatic nerves. In this review, we will investigate the structures of the nervous systems related to the lower urinary tract and the regulatory system of innervation for the urinary storage and micturition and discuss the clinical significance and future prospects of neurourological research.

Metformin and Sildenafil Attenuate Inflammation and Suppress Apoptosis After Ischemia/Reperfusion Injuries in Rat Urinary Bladder.

PURPOSE: Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4-mg/kg metformin and/or 1-mg/kg sildenafil. RESULTS: I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats coadministered metformin and sildenafil and those treated with either agent alone. CONCLUSION: Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.

Impact of Percutaneous Nephrostomy on the Efficacy of in Situ Shock Wave Lithotripsy for Upper Ureteral Stones.

PURPOSE: To investigate whether a Percutaneous nephrostomy (PCN) has any impact on the success rate of shock wave lithotripsy (SWL) and to estimate the probability of stone-free in SWL patients with upper ureter stones. MATERIALS AND METHODS: Overall, 236 patients who underwent SWL for upper ureter stones between 2015 and 2019 were evaluated. Forty-nine patients who underwent PCN during SWL were identified. Medical data of the patients were retrospectively reviewed, and possible prognostic features were evaluated. RESULTS: Out of all patients, 147 patients were selected through propensity score matching. There were no significant differences between the PCN and no PCN groups, except for a lower stone-free rate (55.1% vs. 74.5%, p = .018) and one-session success rate (24.5% vs. 50.0%, p = .003) in the PCN group. In univariate analysis, a younger age, the female sex, a smaller size of stone, lower mean stone density (MSD), and absence of PCN were positive predictive factors of being stone-free in patients who underwent SWL. In multivariate analysis, a smaller size, lower MSD, and absence of PCN were positive predictive factors of being stone-free in patients who underwent SWL. CONCLUSION: Stone size, MSD, and PCN were prognostic factors that influence the outcome of SWL. The presence of PCN during SWL is associated with adverse success rates in patients with upper ureter stones.

Is PSA density of the peripheral zone as a useful predictor for prostate cancer in patients with gray zone PSA levels?

BACKGROUND: Serum prostate-specific antigen (PSA) is widely used in screening tests for prostate cancer. As the low specificity of PSA results in unnecessary and invasive prostate biopsies, we evaluated the clinical significance of various PSAs and PSA density (PSAD) related to peripheral zones in patients with gray zone PSA level (4-10 ng/mL). METHODS: A total of 1300 patients underwent transrectal ultrasonography-guided prostate biopsy from 2014 to 2019. Among them, 545 patients in the gray zone were divided into the prostate cancer diagnosis group and the non-prostate cancer diagnosis group, and PSA, relative extra transitional zone PSA (RETzPSA), estimated post holmium laser enucleation of the prostate PSA (EPHPSA), PSAD, peripheral zone PSA density (PZPSAD) and extra-transitional zone density (ETzD) were compared and analyzed using receiver-operating characteristics (ROC) analysis after 1:1 matching using propensity score. RESULTS: Area under the ROC curve values of PSA, EPHPSA, RETzPSA, PSA density, ETzD, and PZPSAD were 0.553 (95% CI: 0.495-0.610), 0.611 (95% CI: 0.554-0.666), 0.673 (95% CI: 0.617-0.725), 0.745 (95% CI: 0.693-0.793), 0.731 (95% CI: 0.677-0.780) and 0.677 (95% CI: 0.611-0.719), respectively. PSAD had 67.11% sensitivity, 71.71% specificity, and 70.34% positive predictive rate at 0.18 ng/mL/cc. ETzD had 69.08% sensitivity, 64.47% specificity, and 66.04% positive predictive rate at 0.04 ng/mL/cc. When the cut-off value of PSAD was increased to 0.18 ng/mL/cc, the best results were obtained with an odds ratio of 5.171 (95% CI: 3.171-8.432), followed by ETzD with 4.054 (95% CI: 2.513-6.540). CONCLUSIONS: These results suggested that volume-adjusted parameters (ETzD and PSAD) might be more sensitive and accurate than various PSA in gray zone patients who required prostate biopsy to reduce unnecessary biopsy.

Transobturator four-arms mesh in the surgical management of cystocele: a long-term follow-up.

We studied the long-term efficacy and safety of cystocele operation by polypropylene mesh. A total of 198 women with stage ≥2 cystocele who had anterior vaginal wall repair with transobturator four-arm polypropylene mesh during 2003 to 2015 were evaluated. Outcomes including clinical characteristics and complications were reviewed by extracting patient data from electronic medical records. In addition, telephone interviews were conducted using a validated questionnaire along with physical examination. The follow-up period was 9.3±0.3 years. The cystocele stage in patients was significantly decreased post-operation compared to that preoperation. The anatomical cure rate for cystocele was 93.4%, and that for stress urinary incontinence was 95%. Comparing the three questionnaires indicated overall average score was improved significantly, except for Female Sexual Function Index Assessment. Early complications were either resolved spontaneously or controlled medically in four cases of hematoma or abscess, three cases of vaginal infection and urinary tract infection, and four cases of difficult micturition. In late complications, four cases of pain were managed, five cases of recurrence were observed and two cases of mesh exposure were treated with ointment and local excision. Transobturator four-arms mesh is an effective and safe method for cystocele repair with low rate of recurrence and complications. We suggest that the use of transobturator four-arm mesh is a still good choice for the old patients with cystocele who are not suitable for general anesthesia and reside in areas where laparoscopy and robots are not available.

Machine learning prediction of stone-free success in patients with urinary stone after treatment of shock wave lithotripsy.

BACKGROUND: The aims of this study were to determine the predictive value of decision support analysis for the shock wave lithotripsy (SWL) success rate and to analyze the data obtained from patients who underwent SWL to assess the factors influencing the outcome by using machine learning methods. METHODS: We retrospectively reviewed the medical records of 358 patients who underwent SWL for urinary stone (kidney and upper-ureter stone) between 2015 and 2018 and evaluated the possible prognostic features, including patient population characteristics, urinary stone characteristics on a non-contrast, computed tomographic image. We performed 80% training set and 20% test set for the predictions of success and mainly used decision tree-based machine learning algorithms, such as random forest (RF), extreme gradient boosting trees (XGBoost), and light gradient boosting method (LightGBM). RESULTS: In machine learning analysis, the prediction accuracies for stone-free were 86.0, 87.5, and 87.9%, and those for one-session success were 78.0, 77.4, and 77.0% using RF, XGBoost, and LightGBM, respectively. In predictions for stone-free, LightGBM yielded the best accuracy and RF yielded the best one in those for one-session success among those methods. The sensitivity and specificity values for machine learning analytics are (0.74 to 0.78 and 0.92 to 0.93) for stone-free and (0.79 to 0.81 and 0.74 to 0.75) for one-session success, respectively. The area under curve (AUC) values for machine learning analytics are (0.84 to 0.85) for stone-free and (0.77 to 0.78) for one-session success and their 95% confidence intervals (CIs) are (0.730 to 0.933) and (0.673 to 0.866) in average of methods, respectively. CONCLUSIONS: We applied a selected machine learning analysis to predict the result after treatment of SWL for urinary stone. About 88% accurate machine learning based predictive model was evaluated. The importance of machine learning algorithm can give matched insights to domain knowledge on effective and influential factors for SWL success outcomes.

Expression of bladder α1-adrenoceptor subtype after relief of partial bladder outlet obstruction in a rat model.

Purpose: Many patients with benign prostatic hyperplasia require treatment for persistent storage symptoms, even when the obstruction is successfully relieved by surgery. Previous studies identified a characteristic increase in α1D-adrenoceptor levels in the bladder in a bladder outlet obstruction (BOO) model. Here, we investigated the expression of α1-adrenoceptor subtypes in the bladder after relief of partial BOO (pBOO) in a rat model. Materials and Methods: A total of 60 female Sprague-Dawley rats were randomly divided into three groups (sham-operated, pBOO, and pBOO relief groups), and the expression of α1-adrenoceptor subtypes in the urothelium and detrusor muscle tissues was examined by western blot. Results: The expression of the α1D-adrenoceptor was significantly higher in the urothelium and detrusor muscle tissue of the pBOO and pBOO relief groups than in the corresponding tissue of the sham-operated group. Additionally, the α1A-adrenoceptor was predominant in the sham-operated group but significantly decreased in the urothelium in the pBOO group. No significant differences were found in α1A-adrenoceptor levels in detrusor muscle or whole bladder. Conclusions: Our results showed that α1D-adrenoceptor levels were consistently increased with pBOO, even after relief, suggesting that the α1D-adrenoceptor might be a cause of persistent storage symptoms after relief of pBOO.

Changes in Apoptosis-Related Proteins in The Urothelium of Rat Bladder Following Partial Bladder Outlet Obstruction and Subsequent Relief.

PURPOSE: Partial bladder outlet obstruction (PBOO) induces sustained bladder over-distension, leading to ischemia/reperfusion (I/R)-related oxidative damage of the urothelium via apoptosis. The present study aimed to investigate the sequential course of apoptosis in the urothelium of rat bladder and identify the changes in apoptosis-related proteins during PBOO and subsequent relief.  Materials and Methods: The study was conducted using 60 female Sprague-Dawley rats divided into three groups: sham-operated, PBOO only, and PBOO plus subsequent relief. PBOO was induced for 2 weeks, and then the obstruction was relieved by removal of the ligature. The urothelium was assessed by a histological analysis, and expression levels of apoptosis-related proteins were detected by quantitative PCR and immunoblotting. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells were significantly increased in the PBOO only group when compared with the sham-operated group, and decreased in the PBOO relief group when compared with the PBOO group (P < 0.001). From the quantitative PCR and the western blot analyses, expression of Bax, caspase-3, P38, and Jnk was significantly increased in the PBOO group (P < 0.001). However, expression of Erk, Bcl-2 significantly decreased in the PBOO group (P < 0.001). The expression of Erk and Bcl-2 significantly increased in the PBOO relief group when compared with the PBOO group (P < 0.001). In comparison to the sham-operated group, expression levels of survivin significantly increased in both the PBOO and PBOO plus relief groups (P < 0.001). In addition, the expression levels were significantly different between the PBOO and PBOO plus relief groups (P < 0.001). CONCLUSION: PBOO induced apoptosis of urothelium is related to alterations in the MAPK signaling pathways and apoptosis-related protein change. These results may also suggest that the pro-survival Erk signaling cascade and the expression survivin are activated in response to ischemic bladder injury and associated with initiation of bladder restoration in PBOO and subsequent relief. However, the mechanism of survivin as anti-apoptotic protein in ischemic bladder injuries remains unclear.

Oncological and Functional Outcomes of Laparoscopic Radiofrequency Ablation and Partial Nephrectomy for T1a Renal Masses: A Retrospective Single-center 60 Month Follow-up Cohort Study.

PURPOSE: It remains unclear whether laparoscopic radiofrequency ablation (RFA) for primary treatment of small renal masses is similar to partial nephrectomy (PN) in terms of long-term oncological and renal function outcomes. We reviewed the long-term outcomes for patients with T1a renal masses treated with either laparoscopic RFA orPN. MATERIALS AND METHODS: This retrospective single-center study on 115 patients who were treated by laparoscopic RFA or PN for small (<4 cm) renal masses between January 2005 and October 2014 at Chungnam National University Hospital. Estimated glomerular filtration rate (eGFR) was measured before and 1-2 weeks after surgery and at last follow-up. The laparoscopic RFA and PN groups were compared in terms of clinical characteristics data and change in eGFR after surgery using the Chi-squared test or Student's t-test. Survival data were analyzed using theKaplan-Meier method and the log-rank test. RESULTS: Of the 115 patients, 62 and 53 underwent laparoscopic RFA and PN, respectively. Their mean (range) follow-up duration was 60 (30-104) and 68 (30-149) months, respectively (P = 0.092). The RFA patients were older (P = 0.023) and had smaller tumors (P = 0.000). RFA associated with shorter operation and hospitalization times and less perioperative blood loss (all P<0.001). The groups did not differ in terms of change in eGFR 1-2 weeks after surgery (P = 0.252) or at the last follow-up (P = 0.395) or 5 year survival rates (P = 0.360). CONCLUSION: Laparoscopic RFA for small renal masses was comparable to PN in terms of oncological and functional outcomes and associated with shorter operative and hospitalization times and less perioperative bleeding.

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction.

Overactive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient's life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly because of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of sham control and OAB rats. The resulting data revealed the differential expression of 355 proteins in the bladder urothelium of OAB rats compared with sham subjects. Signaling pathway analysis revealed that the differentially expressed proteins were mainly involved in the inflammatory response and apoptosis. Our findings suggest a new target for accurate diagnosis of OAB that can provide essential information for the development of drug treatment strategies as well as establish criteria for screening patients in the clinical environment.

Incidence and risk factors of recurrence of overactive bladder symptoms after discontinuation of successful medical treatment.

PURPOSE: To identify incidence and risk factors of recurrence after discontinuation of successful antimuscarinic therapy in patients with overactive bladder (OAB). MATERIALS AND METHODS: This was a prospective, multicenter trial. Patients who had antimuscarinic agents for more than 12 weeks and showed successful response were enrolled. Successful response was defined as answering 'benefit' for patient perception of treatment benefit and answer lesser than 3 points in patient's perception of bladder condition (PPBC). The enrolled patients discontinued the antimuscarinics, and we evaluated their recurrence with PPBC and OAB symptom score (OABSS) at 1, 3, 6, and 12 months. Primary purpose was to identify the recurrence rate and secondary purpose was to reveal risk factors. RESULTS: Four hundred forty-one patients enrolled and 371 patients completed 6-month follow-up. The enrolled patients showed 1.6 points in PPBC, 2.9 points in OABSS and 1.4 points in IPSS (quality of life) which represented successful response after using antimuscarinics. The cumulative rates of recurrence were 25.6%, 42.3%, and 52.2% at 1, 3, 6 months, respectively. Among 177 patients who did not show recurrence at 6 months, 41 patients were followed up and 4 patients of the 41 patients (9.7%) showed recurrence at 12 months. On univariate and multivariate analyses of recurrence, OAB wet was the risk factor for recurrence after 6 months of discontinuation. CONCLUSIONS: Discontinuation of antimuscarinic therapy after successful treatment resulted in high recurrence rate with time and OAB wet was the independent risk factor for recurrence.

Novel functional roles of caspase-related genes in the regulation of apoptosis and autophagy.

Caspases, a family of cysteine proteases, cleave substrates and play significant roles in apoptosis, autophagy, and development. Recently, our group identified 72 genes that interact with Death Caspase-1 (DCP-1) proteins in Drosophila by genetic screening of 15,000 EP lines. However, the cellular functions and molecular mechanisms of the screened genes, such as their involvement in apoptosis and autophagy, are poorly understood in mammalian cells. In order to study the functional characterizations of the genes in human cells, we investigated 16 full-length human genes in mammalian expression vectors and tested their effects on apoptosis and autophagy in human cell lines. Our studies revealed that ALFY, BIRC4, and TAK1 induced autophagy, while SEC61A2, N-PAC, BIRC4, WIPI1, and FALZ increased apoptotic cell death. BIRC4 was involved in both autophagy and apoptosis. Western blot analysis and luciferase reporter activity indicated that ALFY, BIRC4, PDGFA, and TAK1 act in a p53-dependent manner, whereas CPSF1, SEC61A2, N-PAC, and WIPI1 appear to be p53-independent. Overexpression of BIRC4 and TAK1 caused upregulation of p53 and accumulation of its target proteins as well as an increase in p53 mRNA levels, suggesting that these genes are involved in p53 transcription and expression of its target genes followed by p53 protein accumulation. In conclusion, apoptosis and/or autophagy mediated by BIRC4 and TAK1 may be regulated by p53 and caspase activity. These novel findings may provide valuable information that will aid in a better understanding of the roles of caspase-related genes in human cell lines and be useful for the process of drug discovery.