Osamu Nishizawa

Clinical guidelines for overactive bladder

Department of Urology, Fukushima Medical University, Fukushima, Department of Urology, Shinshu University School of Medicine, Matsumoto, Nagano, Department of Urology, University of Yamanashi Interdisciplinary Graduate School of Medicine and Engineering, Chuo, Yamanashi, Department of Urology, University of Fukui Faculty of Medicine, Fukui, Department of Urology, University of Tokyo Faculty of Medicine, Tokyo, Department of Urology, Asahikawa Medical College, Asahikawa, Hokkaido, Department of Urology, Niigata University School of Medicine, Niigata, Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Department of Urology, Graduate School of Medical Science, Kyushu University, Fukuoka, Department of Urology, Graduate School of medical Science, Kumamoto University, Kumamoto, Japan

Solifenacin as add-on therapy for overactive bladder symptoms in men treated for lower urinary tract symptoms--ASSIST, randomized controlled study.

OBJECTIVESnTo assess the efficacy and safety of solifenacin add-on therapy to tamsulosin in lower urinary tract symptoms (LUTS) men with residual overactive bladder (OAB) symptoms despite tamsulosin monotherapy.nnnMETHODSnIn this randomized, multicenter, double-blind study, male LUTS patients aged≥50 years with urgency episodes/24 hours≥2 and micturitions/24 hours≥8 were randomized to 3 groups: 12-weeks tamsulosin plus placebo (TAM+PBO), tamsulosin plus solifenacin 2.5 mg (TAM+SOL), and tamsulosin plus solifenacin 5 mg (TAM+SOL). Changes from baseline to end of treatment in the number of urgency episodes/24 hours (primary endpoint), micturitions, nocturia, urgency incontinence episodes, International Prostate Symptom Scores (IPSS), and Overactive Bladder Symptom Score (OABSS) were compared between the TAM+SOL groups and TAM+PBO. Safety was assessed on adverse events, postvoid residual volume, and maximal urinary flow rate (Qmax.).nnnRESULTSnSix-hundred thirty-eight men were randomized. Urgency was reduced by 2.2 and 2.4 episodes in the TAM+SOL 2.5 and 5 mg groups, respectively. The TAM+SOL 5 mg group showed significant improvement compared with TAM+PBO (-2.4 vs -1.9, P=.049). The number of micturitions in both TAM+SOL groups were significantly reduced compared with TAM+PBO (both P<.001). IPSS storage symptom score and OABSS significantly improved in both TAM+SOL groups compared with TAM+PBO. Changes in IPSS voiding symptom score and Qmax. were similar in all groups. Four patients (1.9%) in the TAM+SOL 5 mg group had urinary retention, but all recovered after catheterization.nnnCONCLUSIONSnIn male LUTS patients with residual OAB symptoms despite tamsulosin monotherapy, TAM+SOL showed efficacy on urgency, which represents OAB symptoms and was well tolerated.

Autologous bone‐marrow‐derived mesenchymal stem cell transplantation into injured rat urethral sphincter

Objectives:u2003 To evaluate the functional and histological recovery by autologous bone‐marrow‐derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters.

Catheterization: Possible complications and their prevention and treatment

Abstract:u2003 Intermittent catheterization (IC) is a more preferable method for bladder drainage than indwelling urethral or suprapubic catheterization. Several complications with IC have been described, however, including urinary tract infection, genital infection, urethral bleeding, urethritis, urethral stricture, and bladder stones. To prevent these complications, patients should be well instructed on the technique and the risks of IC. Indwelling catheterization should be used only exceptionally, under close control and the catheter should be changed with adequate frequency.

CXCR3 Binding Chemokine and TNFSF14 Over Expression in Bladder Urothelium of Patients With Ulcerative Interstitial Cystitis

PURPOSEnWe investigated the genes responsible for ulcerative interstitial cystitis by DNA microarray analysis and quantitative real-time polymerase chain reaction.nnnMATERIALS AND METHODSnBladder urothelial tissues were taken from a site apart from the ulcerative lesion in 9 patients with ulcerative interstitial cystitis and from a normal-looking area in 9 controls, including 7 with bladder carcinoma and 2 with benign prostatic hyperplasia. Total RNA was extracted from bladder samples and gene expression was compared between these 2 groups using Whole Human Genome DNA microarray 44K (Agilent Technologies, Santa Clara, California). Microarray data were analyzed by GeneSpring GX software and Ingenuity Pathway Analysis. Chosen genes were confirmed for altered transcription by quantitative real-time polymerase chain reaction.nnnRESULTSnWe identified 564 probes that were significantly expressed in mRNA more than 4-fold vs those in controls using volcano plot analysis (p <0.001). Further network Ingenuity Pathway Analysis of these genes showed the top 3 functions, including 1) cell-to-cell signaling and interaction, and hematological system development and function, 2) inflammatory disease and 3) cellular development. Quantitative real-time polymerase chain reaction confirmed increased mRNA expression of several genes in the bladder samples of patients with ulcerative interstitial cystitis, including CXCR3 binding chemokines (CXCL9, 10 and 11) and TNFSF14 (LIGHT).nnnCONCLUSIONSnOur study using DNA microarray analysis followed by quantitative real-time polymerase chain reaction reveals over expression of genes related to immune and inflammatory responses, including T-helper type 1 related chemokines, and cytokines such as CXCR3 binding chemokines and TNFSF14. These genes may be potential interstitial cystitis biomarkers.

Assessment of overactive bladder symptoms: comparison of 3-day bladder diary and the overactive bladder symptoms score.

OBJECTIVESnTo compare the Overactive Bladder Symptom Score (OABSS) and a bladder diary as a tool for assessing symptoms of overactive bladder (OAB).nnnMETHODSnTreatment-naive OAB patients received an antimuscarinic agent, solifenacin. At baseline and 12 weeks after treatment, patients completed a 3-day bladder diary and the OABSS. Relationships between the 2 methods were evaluated by comparison of changes after treatment, agreement between variables and correlation between changes.nnnRESULTSnIn total, 79 patients (42 male and 37 female, mean age 71.1 years) were included in the analysis. Statistically significant improvements were noted for all the OABSS and the corresponding diary variables. The effect size (ES) was largest for the OABSS urgency score (2.00), followed by the OABSS total score (1.54), and then by the diary urgency score (0.92). All of the ESs for the OABSS, except daytime frequency, were larger than those of the corresponding diary variables. The standard response means followed a similar pattern to the ESs. A fairly good agreement between OABSS items and the corresponding diary variables was found at baseline and 12 weeks (kappa coefficient, 0.33-0.80). High correlations (Spearmans rho, ≥ 0.5) between changes in OABSS items and the corresponding diary variables were found for urgency incontinence and night-time frequency.nnnCONCLUSIONSnThe OABSS is highly sensitive to treatment-related changes of OAB symptoms. Because of its simplicity and dependability, the OABSS can be an alternative to a bladder diary for symptom and efficacy assessment in daily clinical practice.

Effects of Nitric Oxide on the Primary Bladder Afferent Activities of the Rat With and Without Intravesical Acrolein Treatment

BACKGROUNDnIt has been suggested that nitric oxide (NO) affects the afferent pathways innervating the bladder. In addition, acrolein, a metabolite of cyclophosphamide, causes bladder hypersensitivity in rats.nnnOBJECTIVEnWe investigated the direct effects of an NO substrate (L-arginine) and an NO synthase inhibitor (N(ω)-nitro-L-arginine methyl ester hydrochloride [L-NAME]) on single fiber activities of the primary bladder afferent nerves with or without acrolein application.nnnDESIGN, SETTING, AND PARTICIPANTSnFemale Sprague-Dawley rats were used. Under urethane anesthesia, a single nerve fiber primarily originating from the bladder was identified by electrical stimulation of the left pelvic nerve and by bladder distention, and it was divided by conduction velocity as Aδ fiber or C fiber.nnnMEASUREMENTSnThe afferent activity measurements with constant bladder filling were repeated three times, and the third measurement served as the baseline observation. After that, two experiments were performed. First, L-NAME (10mg/ml) was instilled intravesically. Then L-arginine (300 mg/kg) was administrated intravenously to investigate the competition with L-NAME. Second, L-arginine was administrated intravenously. Then 0.003% of acrolein or saline was instilled intravesically to obtain another three cycles of instillations.nnnRESULTS AND LIMITATIONSnForty-two single afferent fibers (Aδ fibers: n=19; C fibers: n=23) were isolated in 31 rats. When the bladder was filled with L-NAME solution, afferent activities of both Aδ and C fibers increased significantly, and L-arginine administration inhibited these stimulated responses. In addition, intravenous administration of L-arginine significantly decreased the activities of both fibers during saline instillation. Intravesical acrolein instillation significantly increased the activities of both fibers, which were inhibited by pretreatment with L-arginine.nnnCONCLUSIONSnThe results suggest that NO synthase exists in the rat urinary bladder and clearly demonstrate that L-arginine, an NO substrate, can inhibit both Aδ and C mechanosensitive afferent fibers of the bladder in the rat. In addition, L-arginine can inhibit the activated responses of both fibers to intravesical acrolein.

Randomized Controlled Trial to Treat Benign Prostatic Hyperplasia with Overactive Bladder Using an Alpha-blocker Combined with Anticholinergics

Objectives: TAABO was a randomized, controlled trial to evaluate the efficacy and safety of combination therapy of tamsulosin (TAM) with propiverine (PROP) in men with both benign prostatic hyperplasia and overactive bladder.

Responsiveness and Minimal Clinically Important Change in Overactive Bladder Symptom Score

OBJECTIVEnTo assess the responsiveness and minimal clinically important change (MCIC) in the Overactive Bladder Symptom Score (OABSS), a single score used to quantify overactive bladder symptoms.nnnMETHODSnThe data were derived from a clinical trial of propiverine in patients with overactive bladder. The analysis included participants who completed the OABSS, a bladder diary, and patient-reported outcome measures (urgency and incontinence impact) at baseline and 12 weeks. Responsiveness was assessed with effect sizes, correlations between the OABSS items and bladder diary variables, and comparisons between the score changes and symptom improvement. The MCIC was comprehensively estimated from the discriminating thresholds for minimal symptom improvement, and the receiver operating characteristics curve analyses were used to derive cutoff scores for symptom improvement.nnnRESULTSnA total of 282 participants were included in the present analysis. The effect sizes for the OABSS ranged from -0.369 to -1.485, and correlations between the changes in the OABSS items and the corresponding bladder diary variables were moderate to large. A linear tendency was found between the changes in the OABSS and symptom improvement. The mean change for urgency and incontinence impact was -2.59 and -2.49 for no change and -3.67 and -3.78 for minor improvement, respectively. The optimal cutoff score ranged from -4 to -3. Integrating the MCIC analyses, -3 was estimated as the minimal threshold for a meaningful change.nnnCONCLUSIONnWith good responsiveness, the OABSS is a useful tool for assessing the treatment of OAB symptoms. Furthermore, the results of our study suggest that the MCIC of the OABSS is -3.

Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivity.

Previous studies have suggested that ATP has a role in mechano‐afferent transduction, at least partly mediated by nerves other than capsaicin (Cap)‐sensitive nerves. We investigated the direct effect of ATP on single fiber activity (SFA) of the primary bladder afferent nerves and its relationship with Cap‐sensitivity.