Physiotherapy for continence and muscle function in prostatectomy: a randomised controlled trial.

OBJECTIVE: To assess the effectiveness of pre- and postoperative supervised pelvic floor muscle training (PFMT) on the recovery of continence and pelvic floor muscle (PFM) function after robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We carried out a single-blind randomised controlled trial involving 54 male patients scheduled to undergo RARP. The intervention group started supervised PFMT 2 months before RARP and continued for 12 months after surgery with a physiotherapist. The control group was given verbal instructions, a brochure about PFMT, and lifestyle advice. The primary outcome was 24-h pad weight (g) at 3 months after RARP. The secondary outcomes were continence status (assessed by pad use), PFM function, and the Expanded Prostate Cancer Index Composite (EPIC) score. RESULTS: Patients who participated in supervised PFMT showed significantly improved postoperative urinary incontinence (UI) compared with the control group (5.0 [0.0-908.0] g vs 21.0 [0.0-750.0] g; effect size: 0.34, P = 0.022) at 3 months after RARP based on 24-h pad weight. A significant improvement was seen in the intervention compared with the control group (65.2% continence [no pad use] vs 31.6% continence, respectively) at 12 months after surgery (effect size: 0.34, P = 0.030). Peak pressure during a maximum voluntary contraction was higher in the intervention group immediately after catheter removal and at 6 months, and a longer duration of sustained contraction was found in the intervention group compared with the control group. We were unable to demonstrate a difference between groups in EPIC scores. CONCLUSION: Supervised PFMT can improve postoperative UI and PFM function after RARP. Further studies are needed to confirm whether intra-anal pressure reflects PFM function and affects continence status in UI in men who have undergone RARP.

Effects of a new selective ß3 -adrenoceptor agonist, vibegron, on bladder and urethral function in a rat model of Parkinson's disease.

OBJECTIVES: Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel ß3 -adrenoceptor agonist approved for the treatment of overactive bladder. However, how ß3 -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. METHODS: In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. RESULTS: Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed. CONCLUSIONS: The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of ß3 -adrenoceptor agonists.

Examination of pelvic floor muscle elasticity in patients with interstitial cystitis/bladder pain syndrome using real-time tissue elastography.

INTRODUCTION AND HYPOTHESIS: The aim was to compare pelvic floor muscle (PFM) elasticity between interstitial cystitis/bladder pain syndrome (IC/BPS) patients and healthy women using real-time tissue elastography. METHODS: The subjects were 17 IC/BPS female patients (IC/BPS group; age 34-84 years), 10 healthy middle-aged women (middle-aged group; 50-80 years), and 17 healthy young adult women (young group; 23-37 years). The target sites of elastography were the striated urethral sphincter (SUS) and adipose tissue as the reference site; muscle elasticity was calculated as the strain ratio (SR) of the SUS to the reference site. Evaluations were performed at rest and during PFM contraction. The IC/BPS group completed lower urinary tract symptom and pain questionnaires. SUS SR was compared among the three groups. SUS SR at rest and during PFM contraction was compared among the three groups with the t-test and the Wilcoxon test. Associations between questionnaire results and SUS SR were evaluated by correlation analysis. RESULTS: There was no significant difference in age between the IC/BPS and middle-aged groups, but the young group was significantly younger than the other groups (p < 0.001). SUS SR at rest was significantly higher in the IC/BPS group than in the middle-aged (p = 0.014) and young groups (p = 0.002). Furthermore, in the IC/BPS group, there was no significant difference in SUS SR between at rest and during PFM contraction. SUS SR was not significantly correlated with questionnaire results for lower urinary tract symptoms. CONCLUSIONS: SUS SR at rest was significantly higher in the IC/BPS group than in the young and middle-aged groups.

Can ultrasound measurement of bladder wall thickness be a useful adjunct for regular urodynamics in children with spina bifida?

INTRODUCTION: Spina bifida is a major cause of neurologic bladder dysfunction among children. The goal of neurogenic bladder treatment is to preserve renal function. Close follow-up is essential, as lower urinary tract functions can change with patient growth. Presently, invasive urodynamics is the gold standard for precisely assessing lower urinary tract function. Ultrasound is a low-cost, non-invasive, uncomplicated examination that can be easily repeated. Bladder wall thickness (BWT) measurement by ultrasound has been proposed as a non-invasive alternative for identifying lower urinary tract dysfunctions. OBJECTIVE: Currently there are few reports on BWT in children with spina bifida, and BWT assessment methodology has yet to be defined. The present study aim was to investigate whether BWT could be a useful adjunct for regular urodynamics in children with spina bifida. We especially focused on the precise bladder volume during BWT measurements that were simultaneously performed with urodynamics. STUDY DESIGN: This prospective observational study investigated 33 patients with spina bifida who underwent video urodynamics. We assessed BWT measurements using ultrasound simultaneously performed with video urodynamics. BWT was calculated for the ventral and dorsal walls at 0%, 20%, 40%, 60%, 80%, and 100% of the expected bladder capacity. RESULTS: Median of bladder capacity was 240 mL, and bladder compliance was 19.2 mL/cmH2O. Detrusor overactivity was present in 66.7% and vesicoureteral reflux was present in 27.3% of the patients. BWT of the ventral wall was significantly lower than the dorsal wall. During increases in the bladder volume, both the ventral and dorsal walls exhibited proportional thinning (p < 0.05). There were no significant differences for BWT between males and females. Although there was a higher statistical tendency for detrusor overactivity versus without detrusor overactivity (p = 0.085), there were no significant differences found between patients with and without detrusor overactivity. DISCUSSION: This is the first report where multiple BWT measurements points with video urodynamics were simultaneously performed. Selection of bladder volumes for BWT measurements is critical. Our current study measured six points for each patient during urodynamics. However, available data was not sufficient for detecting bladder function. Until now, there has been no valid standard condition defined for measuring BWT and thus, lack of a standardized method has resulted in discrepancies among studies. CONCLUSION: Our measurement conditions showed BWT may not correlate with the degree of bladder detrusor dysfunction. As BWT ultrasound cannot identify bladder dysfunction of children with spina bifida, this cannot be used as a substitute for invasive urodynamics.

Are sham-operated mice a valid comparator in studies using a bladder outlet obstruction model? A pitfall reveals a meaningful insight.

OBJECTIVE: To evaluate voiding behavior characteristics in intact and sham mice, and to examine whether intact mice show changes in "normal" micturition with aging. METHODS: A total of 72 8-week-old mice were divided into two groups - intact and sham - and the latter group was subjected to a sham of partial bladder outlet obstruction surgery. Urination frequency was evaluated (through metabolic cages) at 1, 2, 3, 6 and 12 months after the surgery (or at the equivalent time points for the intact mice). To address possible mechanisms for aging and surgical effects on urinary behavior, quantitative real-time polymerase chain reaction assays were carried out. Primary data were evaluated using scatter plots and descriptive statistics. RESULTS: In sham mice, urination frequency showed strong variation at the earlier post-surgical time points (especially at 1 month), with variation decreasing with time. Quantitative real-time polymerase chain reaction showed that the serotonin 2C receptor-encoding mRNA accumulated to >28-fold higher levels at 24 months compared with 3 months in intact mice. A major limitation of the quantitative real-time polymerase chain reaction experiments was that we did not separate whole bladder into muscle and mucosa. CONCLUSIONS: Although a sham operation is typically used in partial bladder outlet obstruction experiments to provide control animals, the sham group might itself show increased variation in micturition frequency at early times after surgery, compared with intact animals.

Long-term administration of alpha-1 blocker can reverse the micturition pattern in a bladder outlet obstruction murine model.

OBJECTIVE: To investigate the effect of chronic administration of an alpha-1 blocker on micturition patterns in long-term partial bladder outlet obstruction. METHODS: Mice were divided into three groups: a normal group, in which animals were fed a standard diet; a partial bladder outlet obstruction group, in which the proximal urethra was tied and animals were fed a standard diet; and a partial bladder outlet obstruction + naftopidil group, in which the proximal urethra was tied and animals were fed a standard diet containing naftopidil. Micturition behavior was evaluated in all groups for 6 months after partial bladder outlet obstruction surgery. The parameters evaluated included voided volume, time per void, urination frequency and total urine volume. Quantitative assessment of gene expression was also carried out. RESULTS: Total urine volume, as well as total and average voided volume during night, was significantly decreased in partial bladder outlet obstruction + naftopidil mice compared with partial bladder outlet obstruction animals. The levels of transcripts encoding 5-hydroxytryptamine 2A and tissue inhibitor of metalloproteinase 2 were significantly decreased in the partial bladder outlet obstruction + naftopidil group compared with the partial bladder outlet obstruction group. CONCLUSIONS: Long-term administration of an alpha-1 blocker seems to reverse the disturbance of the micturition pattern caused by partial bladder outlet obstruction. Mechanistically, this effect might be mediated by changes in the expression of a serotonin receptor and/or in the activity of the fibrogenesis pathway.

Bladder outlet obstruction disrupts circadian bladder function in mice.

The circadian clock programs daily rhythms and coordinates multiple behavioural processes, including micturition. Partial bladder outlet obstruction (pBOO) in mice produces hyperactive voiding. However, long-term effects of pBOO on bladder function have not been clarified. In this study, we investigated micturition under conditions of impaired circadian bladder function by inducing long-term pBOO by tying the proximal urethra. Micturition behavior was evaluated at 1, 3, 6 and 12 months after surgery. We used automated voided stain on paper method for a precise micturition recording for mice. And quantitative assessment of gene expression was performed at 24 months after pBOO surgery using qRT-PCR procedure. The micturition frequencies in the pBOO group were significantly decreased at 3, 6, and 12 months compared to those at 1 month after operation in the same group (p < 0.05). Body weight of pBOO mice was significantly increased compared to sham operated mice at 12 months. The expression level of mRNA was exhibited a 3.4-fold nominal increased for a 5-HT2B receptor in the pBOO group compared to the sham group. The current study found that long-term pBOO led to disruption of the circadian bladder function (the day/night cycle) in mice, similar to those observed in human as nocturia. This disruption is possible involvement of the gain of body weight and/or serotonergic alteration after pBOO.

Lower urinary tract function improves after laparoscopic sacrocolpopexy for elderly patients with pelvic organ prolapse.

OBJECTIVES: Pelvic organ prolapse (POP) is relatively common in the elderly population. Laparoscopic sacrocolpopexy (LSC) has been reported by several studies to be a less invasive treatment option as compared to open sacrocolpopexy. However, almost all prior reports focused on the complications or surgical obstacles. The present study was designed to examine POP patients of all ages and assess lower urinary tract function before and after LSC. METHODS: This retrospective study examined the results of LSC performed in POP patients. Urodynamic studies were performed pre- and postoperatively in 50 patients, with the subjects divided into two groups containing those less than and those older than 65 years of age. We performed a pressure flow study. We examined bladder functions by evaluating bladder capacity, detrusor pressure at maximum flow (PdetQmax), maximum flow rate (Qmax), normal desire to void, strong desire to void, voided volume, and postvoid residual volume (PVR). Statistical analysis was performed using Wilcoxon signed rank test. Values of P < .05 were considered significant. RESULTS: With regard to the pressure-flow study parameters, there was a significant increase in the normal desire to void and bladder capacity only in the ≥65 age group. After the operation, there was a significant increase in the mean postoperative Qmax and voided volume, while there was a significant decrease in the PdetQmax and PVR as compared to the preoperative values only in the ≥65 age group. CONCLUSIONS: Results show that in elderly patients with POP, LSC might be a valid option with regard to potentially regaining urinary tract function.

Long-term Outcome of Adenosine A2A Receptor Antagonist on Lower Urinary Tract Symptoms in Male Parkinson Disease Patients.

OBJECTIVES: In addition to motor symptoms, bladder dysfunction is a major clinical issue in patients with Parkinson disease (PD). Istradefylline is adenosine A2A receptor antagonist approved for PD patients with wearing-off symptoms. The aim of this study was to determine the long-term effects of istradefylline on lower urinary tract symptoms (LUTSs) in PD patients. METHODS: We enrolled 14 male PD patients. The mean age of patients was 73 years (61-77 years), the Hoehn-Yahr stage was 2 (2-3), and disease duration was 9 years (3-28 years). The effects of istradefylline (20 mg/d) on LUTSs in PD patients with motor complications after 3, 6, and 12 months of therapy were evaluated based on the International Prostate Symptom Score and Overactive Bladder Symptom Score before and after its administration. RESULTS: Motor symptoms significantly improved at 12 months' administration (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III: 30.0 ± 12.9 vs 13.8 ± 8.1; P < 0.01). Significant improvements were also observed in the answers provided on urinary questionnaires (International Prostate Symptom Score, 14.4 ± 7.6 vs 8.5 ± 6.8; Overactive Bladder Symptom Score, 6.9 ± 2.8 vs 5.5 ± 3.7; P < 0.05). Nighttime urinary frequency and the percentage of the nocturnal urine volume also improved significantly at 3 months' administration (P < 0.01). CONCLUSIONS: Istradefylline effectively improved not only motor symptoms, but also LUTSs in patients with PD.

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research.

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value.

Clinical and urodynamic assessment in patients with pelvic organ prolapse before and after laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: We hypothesized that patient-reported urinary symptoms and urodynamic evaluation improve after laparoscopic sacrocolpopexy (LSC) despite deeper vesicovaginal space dissection. METHODS: This was a retrospective study of women with pelvic organ prolapse who underwent LSC from January 2013 to January 2016 in a tertiary center. Urinary function was clinically evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), the Overactive Bladder Symptom Score (OABSS) and the Pelvic Floor Distress Inventory Questionnaire- - Short Form 20 (PFDI-20). Urodynamic assessment was performed before and 6 months after surgery. The Wilcoxon signed-ranks test and the McNemar test were applied with p < 0.05 considered significant. RESULTS: A total of 155 patients were included in the study. Of these, 46 had urodynamic assessment before and after LSC. There were significant improvements after LSC in urodynamic storage phase parameters (higher volume at first desire, higher volume at strong desire, and larger bladder capacity) and voiding phase parameters (higher Q max, higher Q ave, lower P det Q max, increased voided volume and reduced postvoid residual urine volume). Clinically, there was a significant increase after LSC in stress urinary incontinence and a significant reduction in urgency urinary incontinence, overactive bladder and voiding dysfunction. CONCLUSIONS: Apart from increased stress urinary incontinence, there was an improvement in overall urinary function in terms of patient-reported symptoms and urodynamics, despite deep vesicovaginal space dissection. Hence, LSC is a viable surgical option for pelvic organ prolapse, restoring both level 1 and level 2 support without detrimental effects on urinary function.