EarlyTect BCD, a Streamlined PENK Methylation Test in Urine DNA, 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.

The epidemiology of male lower urinary tract symptoms associated with benign prostatic hyperplasia: Results of 20 years of Korean community care and surveys.

PURPOSE: To investigate the prevalence of lower urinary tract symptoms/benign prostatic hyperplasia in a Korean population. MATERIALS AND METHODS: The Korean Prostate & Voiding Health Association provided free prostate-related community health care and conducted surveys in all regions of Korea from 2001 to 2022 with the cooperation of local government public health centers. A total of 72,068 males older than 50 were surveyed and analyzed. History taking, International Prostate Symptom Score (IPSS), transrectal ultrasonography, prostate-specific antigen (PSA) testing, uroflowmetry, and urine volume testing were performed. RESULTS: The mean prostate volumes in males in their 50s, 60s, 70s, and 80s or above were 24.7 g, 27.7 g, 31 g, and 33.7 g, respectively. The proportion of males with high PSA greater than 3 ng/mL was 3.8% among males in their 50s, 7.7% among males in their 60s, 13.1% among males in their 70s, and 17.9% among males 80 years of age or older. The mean IPSS total scores in males in their 50s, 60s, 70s, and 80s or above were 10.7, 12.7, 14.5, and 16, respectively. Severe symptoms were reported by 27.3% of males, whereas 51.7% reported moderate symptoms. The mean Qmax in males in their 50s, 60s, 70s, and 80s or above were 20 mL/s, 17.4 mL/s, 15.4 mL/s, and 13.8 mL/s, respectively. CONCLUSIONS: In this population-based study, mean prostate volume, IPSS, PSA, and Qmax were 30.6±15.1 g, 14.8±8.2, 1.9±4.7 ng/mL, and 15.6±6.5 mL/s, respectively. Aging was significantly associated with increased prostate volume, PSA levels, and IPSS scores, and with decreased Qmax and urine volume.

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.

Development and Evaluation of Urolithiasis Detection Technology Based on a Multimethod Algorithm.

PURPOSE: In this paper, we propose an optimal ureter stone detection model utilizing multiple artificial intelligence technologies. Specifically, the proposed model of urinary tract stone detection merges an artificial intelligence model and an image processing model, resulting in a multimethod approach. METHODS: We propose an optimal urinary tract stone detection algorithm based on artificial intelligence technology. This method was intended to increase the accuracy of urinary tract stone detection by combining deep learning technology (Fast R-CNN) and image processing technology (Watershed). RESULTS: As a result of deriving the confusion matrix, the sensitivity and specificity of urinary tract stone detection were calculated to be 0.90 and 0.91, and the accuracy for their position was 0.84. This value was higher than 0.8, which is the standard for accuracy. This finding confirmed that accurate guidance to the stones area was possible when the developed platform was used to support actual surgery. CONCLUSION: The performance evaluation of the method proposed herein indicated that it can effectively play an auxiliary role in diagnostic decision-making with a clinically acceptable range of safety. In particular, in the case of ambush stones or urinary stones accompanying ureter polyps, the value that could be obtained through combination therapy based on diagnostic assistance could be evaluated.

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.

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.

Irreversible Bladder Remodeling Induced by Fibrosis.

Underactive bladder and impaired bladder compliance are irreversible problems associated with bladder fibrosis. Remodeling of the extracellular matrix is regarded as an important mechanism associated with bladder fibrosis. However, various risk factors and conditions contribute to the functional impairment of the bladder associated with fibrosis, and there is limited knowledge about bladder fibrosis-associated problems in the field of neurourology. Further studies are thus necessary to elucidate the underlying mechanism of bladder fibrosis and to identify effective treatment.

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.

Adenosine A2A Receptor Agonist Polydeoxyribonucleotide Alleviates Interstitial Cystitis-Induced Voiding Dysfunction by Suppressing Inflammation and Apoptosis in Rats.

BACKGROUND: Interstitial cystitis (IC) is a chronic disorder that indicates bladder-related pain or discomfort. Patients with IC often experience urination problems, such as urinary frequency and urgency, along with pain or discomfort in the bladder area. Therefore, new treatments based on IC etiology are needed. Polydeoxyribonucleotide (PDRN) is a biologic agonist of the adenosine A2A receptor, and PDRN has anti-inflammatory effect and inhibits apoptosis. In the current study, the effect of PDRN on cyclophosphamide-induced IC animal model was investigated using rats. METHODOLOGY: To induce the IC animal model, 75 mg/kg of cyclophosphamide was injected intraperitoneally once every 3 days for 10 days. The rats in the PDRN-treated groups were intraperitoneally injected with 0.5 mL physiological saline containing 8 mg/kg PDRN, once a day for 10 days after IC induction. RESULTS: Induction of IC by cyclophosphamide injection caused voiding dysfunction, bladder edema, and histological damage. Cyclophosphamide injection increased secretion of pro-inflammatory cytokines and enhanced apoptosis. In contrast, PDRN treatment alleviated voiding dysfunction, bladder edema, and histological damage. Secretion of pro-inflammatory cytokines and expressions of apoptotic factors were suppressed by PDRN treatment. These changes indicate that treatment with PDRN improves voiding function by ultimately promoting the repair of damaged bladder tissue. CONCLUSION: The conclusion of this experiment suggests the possibility that PDRN could be used as an effective therapeutic agent for IC.

Past, Present, and Future in the Study of Neural Control of the Lower Urinary Tract.

The neurological coordination of the lower urinary tract can be analyzed from the perspective of motor neurons or sensory neurons. First, sensory nerves with receptors in the bladder and urethra transmits stimuli to the cerebral cortex through the periaqueductal gray (PAG) of the midbrain. Upon the recognition of stimuli, the cerebrum carries out decision-making in response. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs) and UMNs coordinate storage and urination in the brainstem for synergic voiding. In contrast, LMNs, which originate in the spinal cord, cause muscles to contract. These neurons are present in the sacrum, and in particular, a specific neuron group called Onuf's nucleus is responsible for the contraction of the external urethral sphincter and maintains continence in states of rising vesical pressure through voluntary contraction of the sphincter. Parasympathetic neurons originating from S2-S4 are responsible for the contraction of bladder muscles, while sympathetic neurons are responsible for contraction of the urethral smooth muscle, including the bladder neck, during the guarding reflex. UMNs are controlled in the pons where various motor stimuli to the LMNs are directed along with control to various other pelvic organs, and in the PAG, where complex signals from the brain are received and integrated. Future understanding of the complex mechanisms of micturition requires integrative knowledge from various fields encompassing these distinct disciplines.

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.

Efficacy of an Alpha-Blocker for the Treatment of Nonneurogenic Voiding Dysfunction in Women: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: To evaluate the efficacy of an alpha-1 adrenergic receptor (α1-AR) blocker for the treatment of female voiding dysfunction (FVD) through a pressure-flow study. METHODS: This was a randomized, double-blind, placebo-controlled trial. Women aged ≥18 years with voiding symptoms, as defined by an American Urological Association symptom score (AUA-SS) ≥15 and a maximum flow rate (Qmax) <15 mL/sec with a voided volume of >100 mL and/or a postvoid residual (PVR) volume >150 mL, were randomly allocated to either the alfuzosin or placebo group. After 8 weeks of treatment, changes in the AUA-SS, Bristol female lower urinary tract symptoms (BFLUTS) questionnaire, Qmax/PVR, and voiding diary were compared between groups. Patients' satisfaction with the treatment was compared. Patients were categorized into 3 groups according to the Blaivas-Groutz bladder outlet obstruction (BOO) nomogram: none, mild, and moderate to severe. Subgroup comparisons were also made. RESULTS: Of a total of 187 women, 154 (79 alfuzosin, 75 placebo) were included in the analysis. After 8 weeks of treatment, the AUA-SS decreased by 7.0 in the alfuzosin group and by 8.0 in the placebo group. Changes in AUA-SS subscores, BFLUTS (except the I-sum), the voiding diary, and Qmax/PVR were not significantly different between groups. Approximately 54% of the alfuzosin group and 62% of the placebo group were satisfied with the treatment. No significant difference was observed between groups according to the presence or grade of BOO. CONCLUSIONS: Alfuzosin might not be more effective than placebo for treating FVD. The presence or the grade of BOO did not affect the results. A further study with sufficient power is needed to determine the efficacy of α1-AR blockers for the treatment of FVD.

Clinicopathological Profiling of LC3B, an Autophagy Marker, and ESRRA (Estrogen-related Receptor-alpha) in Muscle-invasive Bladder Cancer.

BACKGROUND/AIM: Microtubule-associated protein 1 light chain 3B (LC3B), an autophagy marker, has been used as a promising marker in various cancer types. However, the expression of LC3B in muscle-invasive bladder cancer (MIBC) and its prognostic significance have not been investigated. Recent studies pointed to the involvement of ESRRA in regulating autophagy via both transcriptional and post-translational control. In the current study, prognostic importance of LC3B and ESRRA in MIBC was investigated. PATIENTS AND METHODS: We immunohistochemically studied the expression of LC3B and ESRRA in 56 MIBC samples. RESULTS: LC3B was stained high in 16 patients (28.6%) and low or negative in 40 patients (71.4%). ESRRA expression was high for 20 patients (35.7%) and low for 36 patients (64.3%). Both LC3B (p=0.003) and ESRRA (p=0.026) expression correlated significantly with disease-free survival rates. Double-positive LC3B and ESRRA correlated with poor overall survival (p=0.007) and disease-free survival (p=0.001) in MIBC patients. CONCLUSION: LC3B and ESRRA might be a useful prognostic factor in patients with MIBC. The co-expression of LC3B and ESRRA might be a prognostic and therapeutic target for patients with bladder cancer.

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.

Low-frequency electroacupncture improves locomotor function after sciatic crushed nerve injury in rats.

Sciatic crushed nerve injury (SCI) causes pain-related gait and swelling in the affected limb. Electroacupuncture (EA) is a modified acupuncture technique, and analgesic effect of EA on different types of pain has been documented. Scientific functional index (SFI) is a mathematical formula to represent parameters of normal and experimental footprints. We investigated the effect of low-frequency EA on functional recovery following SCI in rats. For this study, immunohistochemistry for c-Fos in the ventral lateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) and western blot for neurofilament (NF) and brain-derived neurotrophic factor (BDNF) in the sciatic nerve were conducted. To induce crush injury on the sciatic nerve, sciatic nerve was crushed for 30 sec using a surgical clip. The rats in the acupuncture groups received acupuncture bilaterally at respective site, once a day for 14 days. The rats in the EA group received 100-Hz electrical stimulation for 10 min once a day during 14 days. SCI decreased SFI value, in contrast, EA increased SFI value. c-Fos expression in the vlPAG and PVN was increased following SCI, in contrast, EA suppressed c-Fos expression. NF expression in the sciatic nerve was decreased by SCI, in contrast, EA increased NF expression. BDNF expression in the sciatic nerve was increased by SCI, in contrast, EA suppressed BDNF expression. In the present study, EA showed effectiveness on functional recovery from SCI.