Yong Gil Na

APE1/Ref-1 as a Serological Biomarker for the Detection of Bladder Cancer

Purpose Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in a number of cancers. We attempted to determine whether serum APE1/Ref-1 is elevated in patients with bladder cancer. Materials and Methods Serum APE1/Ref-1 levels were determined using enzyme-linked immunosorbent assay in serum from patients with bladder cancer who had not received chemotherapy or radiotherapy (n=51) and non-tumor controls (n=55). The area under the receiver operating characteristic area under the curve was applied to determine the correlation between clinical factors and the serum levels of APE1/Ref-1. Results Serum levels of APE1/Ref-1 in bladder cancer patients were significantly elevated compared to those of the control group (3.548±0.333 ng/100 μL [n=51] for bladder cancer vs. 1.547±0.319 ng/100 μL [n=55] for the control group), with a sensitivity and specificity of 93% and 59%, respectively. Serum APE1/Ref-1 levels are associated with tumor stage, grade, muscle invasion, and recurrence. Conclusion Serum APE1/Ref-1 might be useful as a potential serologic biomarker for bladder cancer.

Expression of Nitric Oxide Synthase and Aquaporin-3 in Cyclophosphamide Treated Rat Bladder

PURPOSE The expression of Nitric oxide Synthase (NOS) and aquaporin (AQP) water channels in rat bladder is recently reported. The aim of this study is to evaluate the expression of inducible NOS (iNOS), aquaporin-3 (AQP-3) in cyclophosphamide (CYP) induced rat bladder. MATERIALS AND METHODS The 32 Sprague-Dawley rats were divided into cystitis group (n=20) and control group (n=12). In cystitis group, 100mg/kg CYP was injected every second day for 1 week whereas in control group, normal saline was injected. After extracting of the bladder and dividing dome, body and trigone of the bladder, independently H&E staining and immunohistochemical staining for iNOS and AQP-3 were performed. Expressions of iNOS and AQP-3 were analyzed with a confocal laser scanning microscope and an image analyzer. RESULTS The expression of iNOS significantly increased in the mucosa, submucosa layer of dome in cystitis group (p<0.05). The expression of AQP-3 significantly increased in the mucosa, submucosa, vessel layer of dome in cystitis group (p<0.05). CONCLUSIONS These results suggest that inflammatory change activates NOS and AQP-3 expression in the bladder tissue of rats. These may imply that NOS and AQP-3 have a pathophyiological role in the cyclophophamide induced interstitial cystitis. Further study on the NOS and AQP-3 in bladder is needed for clinical application.

Safety and efficacy of 8-mg once-daily vs 4-mg twice-daily silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (SILVER Study): a 12-week, double-blind, randomized, parallel, multicenter study.

OBJECTIVE To show the noninferiority of silodosin 8-mg once-daily (QD) to 4-mg twice-daily (BID) in efficacy and safety in patients with lower urinary tract symptoms or benign prostatic hyperplasia in the Korean population. METHODS A prospective, multicenter, double-blind, randomized, comparative study was conducted. A total of 532 male patients aged ≥50 years with lower urinary tract symptoms or benign prostatic hyperplasia were included. All patients received silodosin QD or BID for 12 weeks. The primary end point was the change from baseline in total International Prostate Symptom Score (IPSS) at 12 weeks. Adverse drug reactions, vital signs, and laboratory tests were recorded. RESULTS A total of 424 patients were randomized to the silodosin QD or BID groups. These groups were not significantly different in baseline characteristics. The mean total IPSS change in QD group was not inferior to that in BID group (-6.70 and -6.94, respectively; 95% confidence interval, -0.88 to 1.36). The QD and BID groups did not significantly differ in the following: percentages of patients with ≥25% (63.41% and 67.82%, respectively; P = .349) or ≥4-point improvement in total IPSS (65.85% and 69.31%, respectively; P = .457), maximum urinary flow rate improvement ≥30% (47.32% and 40.59%, respectively; P = .172), changes in IPSS voiding subscore (-4.42 ± 4.93 and -4.65 ± 4.77; P = .641), IPSS storage subscore (-2.05 ± 3.07 and -2.52 ± 2.97; P = .117), quality of life (-1.19 ± 1.49 and -1.40 ± 1.42; P = .136), maximum urinary flow rate (3.55 ± 5.93 and 3.74 ± 6.79 mL/s; P = .768), International Continence Society male questionnaire score, Patient Goal Achievement Score, or Treatment Satisfaction Question. The 2 groups had similar frequencies of adverse drug reactions. CONCLUSION QD administration of silodosin was not inferior to BID in efficacy. The 2 groups had similar adverse drug reaction profiles.

Comparison of Laparoscopic Radiofrequency Ablation and Open Partial Nephrectomy in Patients With a Small Renal Mass

Purpose We have performed both open partial nephrectomy (OPN) and laparoscopic radiofrequency ablation (RFA) on selected patients since January 2007 and have been following these patients through serial laboratory assessments and computed tomography (CT). The purpose of the present study was to evaluate long-term oncologic outcomes and renal function status for laparoscopic RFA versus OPN at a minimum follow-up of 3 years. Materials and Methods A total of 55 patients with exophytic, single small renal masses were treated with either OPN (n=14) or laparoscopic RFA (n=41) by a single surgeon. The indications for laparoscopic RFA were as follows: 1) cases with the greatest dimension of the renal mass <3 cm, and 2) cases in which the collecting system, renal calyx, and great vessels were free from the tumor margins by 1 cm. Results The estimated blood loss (EBL), the operation time, and the mean number of hospital days was significantly lower in the laparoscopic RFA group than in the OPN group. Oncologic data did not differ significantly between the two groups. Creatine clearance levels did not differ significantly compared with those before the operation in either group. Conclusions Our data suggest excellent therapeutic outcomes with laparoscopic RFA with achievement of effective operative times, hospital stays, and EBL compared with OPN. According to our indications for laparoscopic RFA, laparoscopic RFA is an effective minimally invasive therapy for the treatment of small renal masses, yielding oncologic outcomes and renal function equivalent to those of OPN.

Comparison of TOA and TOT for Treating Female Stress Urinary Incontinence: Short-Term Outcomes

Purpose The transobturator adjustable tape (TOA) sling operation is a new procedure that allows for the adjustment of tension after surgical intervention, thus permitting correction of postoperative incontinence or obstruction. The aim of this study was to compare the efficacy and safety of TOA with that of the transobturator tape (TOT) procedure. Materials and Methods Between 2008 and 2009, women with stress urinary incontinence (SUI) underwent TOT (n=63) or TOA (n=40). The preoperative evaluation included history taking, physical examination, voiding diary, stress and 1-hour pad tests, and a comprehensive urodynamic examination. Postoperative evaluation was performed at the 1-week and 3-month postoperative follow-up visits. Results The overall cure rate was 90.0% for the TOA group and 85.7% for the TOT group. The rate of satisfaction was higher in the TOA group than in the TOT group (95.0% vs. 85.6%). Four patients in the TOA group needed reduced tension as the result of urinary obstruction. The tension of the mesh was tightened in 1 patient because of a certain degree of continuing incontinence. The residual urine volume was significantly lower in the TOA group than in the TOT group (7.8 ml vs. 43 ml, p=0.01). Conclusions TOA allowed postoperative readjustment for a number of days after surgical intervention, which allowed for good short-term treatment outcomes. These data suggest that better subjective and objective results and residual urine volume can be obtained in the TOA group than those achieved with the traditional non-adjustable mesh and without significant postoperative complications.

Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker

Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

A Comparison of the Clinical Efficacy of the Transobturator Adjustable Tape (TOA) and Transobturator Tape (TOT) for Treating Female Stress Urinary Incontinence with Intrinsic Sphincter Deficiency: Short-term Results

Purpose The transobturator adjustable tape (TOA) allows adjustment of tension after surgical intervention, thus permitting correction of postoperative incontinence or obstruction. The aim of this study was to compare the efficacy and safety of TOA versus transobturator tape (TOT) for the treatment of stress urinary incontinence with intrinsic sphincter deficiency (ISD). Materials and Methods Patients underwent TOA (n=33 with ISD) or TOT (n=47 with ISD) insertion by one experienced surgeon. The patients were considered to have ISD on the basis of a Valsalva leak point pressure <60 cmH2O or a maximum urethral closure pressure <20 cmH2O. The preoperative evaluation included history taking, physical examination, voiding diary, stress and 1-hour pad tests, and a comprehensive urodynamic examination. Postoperative evaluation included a stress test, 1-hour pad test, questionnaire, and uroflowmetry with postvoid residuals. Results After 6 months of follow-up, the rate of cure (TOA, 75.6% vs. TOT, 72.3%) was similar between the two groups. The rate of satisfaction was not significantly higher in the TOA group than in the TOT group (84.8% vs. 78.7%; p=0.05). Four patients in the TOA group (12.1%) needed a reduction in tension because of urinary obstruction (flow <10 ml/sec and/or residual urine >50 ml). The tension of the mesh was tightened in 5 patients (15.2%) because of the persistence of a certain degree of incontinence. The residual urine volume at postoperative 7 days was significantly lower in the TOA group than in the TOT group (19.5 ml vs. 41 ml; p=0.016, repeated-measures analysis of variance test). Conclusions The TOA allows postoperative readjustment of the suburethral sling pressure for a number of days after surgical intervention, which allows for the achievement of good short-term results. These data suggest that better lower obstructive voiding symptoms than those achieved with the traditional nonadjustable mesh can be obtained with the TOA.

Prospective Study Comparing the Suprapubic Arc (Sparc) Procedure and the Transobturator (Monarc) Procedure for Treating Female Stress Urinary Incontinence

Objectives: In a comparative trial we evaluated the efficacy and safety of the suprapubic arch (Sparc) and transobturator (Monarc) procedures for the treatment of female stress urinary incontinence (SUI).

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 patients 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.

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.