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Background: Guillain-Barré syndrome (GBS) as acute inflammatory demyelinating polyradiculoneuropathy frequently leads to lower urinary tract dysfunction. The available knowledge in the medical literature is limited and good recommendations for diagnosis and therapy are rare., Materials and Methods: In this study, 189 patients with GBS were screened for lower urinary tract dysfunction. In symptomatic patients, a urodynamic study was performed. Detrusor contractility, post-void residual, and changes of the symptoms over time were studied. Overall Barthel index and urinary control Barthel index as well as the relationship of time after onset of the disease and post-void residual were studied as possible screening criteria for urodynamic assessment., Results: According to the urinary control Barthel index (BI), 115 of 189 patients (61%) presented lower urinary tract symptoms sometime during the course of disease. In 28 patients, these symptoms were temporary during the acute phase. At the time of urological assessment, 87 patients had lower urinary tract symptoms. At the end of rehabilitation, 37 had no symptoms anymore (BI 10), 20 were able to control micturition to a certain extent (BI 5), and 30 had no lower urinary tract control (BI 0). There was a significant negative correlation between post-void residual volume and overall BI (ρ -0.5823, p < 0.0001) and BI for urinary tract control (ρ -0.6430, p < 0.0001)., Conclusions: Overall BI and BI for urinary tract control are suitable screening criteria for urodynamic assessment.

Cystometrography (CMG) is a means of studying bladder pressure. It is a very useful diagnostic tool in patients with lower urinary tract symptoms for which a simple cystoscopy will not offer sufficient information to form a diagnosis. Of the 8893 patients who underwent screening for urological conditions in rural northeast India during 2010-2014, 280 with lower urinary tract symptoms were investigated with a combination of cystoscopy and CMG. By corresponding CMG diagnosis and treatment, we could examine patients' overall satisfaction with both the procedure and the treatment. We describe a low-cost method of CMG and our results using this method in rural areas of India.

Objective: To develop and validate a nomogram for assessing bladder outlet obstruction (BOO) in women derived from concurrent P det.Qmax and Q max based on radiographic evidence of increased urethral resistance., Patients and Methods: Retrospective analysis of prospectively acquired video-urodynamics and clinical data of 185 women (development cohort) was performed. The P det.Qmax were plotted against Q max and cluster analysis was performed to determine an axis that best divided the definitively obstructed and unobstructed. Using data from a further 350 women (validation cohort), the sensitivity and specificity of the derived criterion was calculated. Finally, the data from both groups was pooled together and using binary logistic regression analysis, a nomogram was produced., Results: Of the 535 patients in the two cohorts, (122 [22.8%]) demonstrated radiographic evidence of BOO. Cluster analysis identified the axis that best separates the radiographically obstructed and unobstructed as P det.Qmax  = 2*Q max . Using the data from the validation cohort, the sensitivity and specificity for this was calculated as 0.94 and 0.93, respectively. A nomogram, representing the probability of BOO for concurrent P det.Qmax and Q max measurements was derived by pooling data from both cohorts. Alternatively, a female BOO index (BOOIf) may be calculated mathematically using the formula BOOIf = P det.Qmax  - 2.2*Q max, that is, BOOIf < 0, <10% probability of obstruction, BOOIf > 5 likely obstructed (50%) and If BOOIf > 18, obstruction almost certain (>90%)., Conclusion: A female BOO nomogram (the SG nomogram) with high sensitivity and specificity is proposed. The nomogram can be used to stratify the degree of BOO or assess response to treatment., (© 2017 Wiley Periodicals, Inc.)

It is well known that lower urinary tract symptoms (LUTS) have a multifactorial etiology. Therefore, there is an increased need for improved diagnostics for the optimal assessment of patients with LUTS in order to identify the various causes of symptoms and improve disease phenotyping. Research has focused on the development of improved urodynamic technologies and the development of noninvasive tests that could replace urodynamic studies. This mini-review will present the most recently published studies on the topic including new technologies in the diagnosis of bladder outlet obstruction, novel metrics for bladder sensation, analysis of filling phase rhythm, measurement of detrusor wall tension, and brain imaging during urodynamic studies., Patient Summary: Lower urinary tract symptoms (LUTS) have a multifactorial etiology; therefore there is a need for the development of new tests that can help LUTS diagnosis. The present mini-review highlights the new tests and novel concepts in the field., (Copyright © 2018. Published by Elsevier B.V.)

Urodynamics can distinguish bladder outlet obstruction from detrusor underactivity. Clear identification of the mechanism of a man's voiding symptoms can help give the best chance of good outcome from surgery. Publication of results from the UPSTREAM study will help in establishing the exact place for urodynamic testing in male lower urinary tract symptoms., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (© 2017 The Japanese Urological Association.)

Objectives: Lower urinary tract symptoms (LUTS) in men result from a complex interplay of pathophysiology, including bladder and bladder outlet dysfunction. This study retrospectively analyzed bladder dysfunction in men with LUTS based on the results of video-urodynamic studies (VUDS)., Methods: Male patients (aged ≥40 years), with LUTS and an International Prostate Symptom Score of 8 or more, who were refractory to alpha-blocker treatment were retrospectively recruited and evaluated with VUDS and total prostate volume (TPV). Patients were further divided into subgroups of bladder dysfunction and bladder outlet dysfunction according to characteristic VUDS findings. Age, TPV and VUDS findings were compared among different subgroups., Results: After VUDS, bladder outlet obstruction (BOO) was only noted in 48.6% of men. Of patients, 919 of 2991 (30.7%) had bladder dysfunction including detrusor underactivity (DU, 5.1%), detrusor overactivity and inadequate contractility (DHIC, 5.3%), detrusor overactivity (DO, 17%) and hypersensitive bladder (HSB, 3.3%). In addition, 1941 (64.9%) had bladder outlet dysfunction including BOO + DO (33.8%), BOO alone (14.8%), and poor urethral sphincter relaxation (PRES, 16.3%). Among the 1519 patients with DO, 66.6% (1012) had BOO while, among 1454 patients with BOO, 69.5% (1010) had DO. Patients with DHIC, DU and DO were 5 years older than patients with HSB and normal men. TPV was significantly smaller in patients with DHIC, DU and DO as compared with BOO + DO., Conclusion: Approximately one-third of male LUTS was due to bladder dysfunction. A man older than 70 years with LUTS and TPV less than 30 mL usually indicates the presence of bladder dysfunction rather than BOO., (© 2016 John Wiley & Sons Australia, Ltd.)

Purpose: To determine success rate (SR), functional outcome, and patient satisfaction of a modified YV-plasty for reconstruction of the bladder neck in case of recurrent bladder neck stenosis (BNS) after transurethral surgery of the prostate: the T-plasty., Patients and Methods: We identified all patients who underwent T-plasty at our center between December 2008 and July 2016. Patients' charts were reviewed. Patients were queried by telephone and by mail at time of follow-up (FU). Primary endpoint was SR. Secondary endpoints were complications, continence, satisfaction, and changes in quality of life measured by validated questionnaires., Results: Thirty patients underwent the T-plasty. Median age at surgery was 69 (IQR 62-73) years. Most patients had BNS due to TUR-P [n = 25 (83.3%)]. No severe blood loss or severe complications occurred perioperatively. Median FU was 45 (IQR 18-64) months. Three patients were lost to FU. Success rate was 100%. Compared to pre-OP Q max , mean Q max post-OP improved significantly [pre-OP 6.79 (SD ± 4.76) ml/s vs post-OP was 24.42 (SD ± 12.61) ml/s; (t(5) = 4.12, p = 0.009)]. Mean post-void residual urine decreased significantly [pre-OP 140.77 (SD ± 105.41) ml vs post-OP 14.5 (SD ± 22.42) ml; (t(9) = -3.86, p = 0.004)]. One patient developed a de-novo-incontinence post-OP. Mean ICIQ-SF Score was 1.2 (SD ± 2.27). 88.5% of patients were pleased or delighted by surgery. 75% of patients claimed their quality of life has been (strongly) improved., Conclusions: The T-plasty is a valuable option as treatment of recurrent BNS. SR, rates of continence, and high patient satisfaction are very encouraging.

Background: Few studies have focused on the urodynamic findings of urethral diverticula (UD). We characterized the symptoms and urodynamic findings in women with UD., Methods: A retrospective review of all women in a single center having surgical treatment for symptomatic UD between May 2004 and September 2014 was done. Lower urinary tract symptoms were evaluated with International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires. All patients underwent magnetic resonance imaging and videourodynamic study (VUDS) prior to surgery, and postoperative evaluation with VUDS., Results: A total of 20 female patients were enrolled into the study. 12 (60%) UD patients presented with symptoms of stress urinary incontinence (SUI). However, there were merely 3 (15%) patients diagnosed as urodynamic SUI. 15 (75%) patients exhibited low catheter-free uroflow. Detrusor overactivity was demonstrated in 4 (20%) patients. Bladder outlet obstruction (BOO) was diagnosed in 8 (40%) cases. Postoperative VUDS revealed persistent BOO in 50% of patients with preoperative BOO. Of these, residual diverticulum was noted by VUDS in one patient., Conclusion: For UD patients with urinary incontinence or voiding dysfunction, VUDS is helpful in accurately characterizing these symptoms., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Aims: Voiding dysfunction due to dysfunctional voiding (DV) and poor relaxation of the external sphincter (PRES) are commonly found among adult women with lower urinary tract symptoms (LUTS) during videourodynamic study (VUDS). This study analyzed the VUDS characteristics of DV and PRES in female voiding dysfunction., Methods: This retrospective study involved 1914 women aged >18 years with refractory LUTS. The medical records and the VUDS parameters were reviewed. Patients diagnosed with DV and PRES participated in the study. The VUDS characteristics and urethral sphincter activities were compared with those of urodynamically normal women., Results: Of the 1914 women, 325 (17.0%) and 336 (17.6%) were diagnosed with DV and PRES, respectively. Detrusor overactivity (DO) occurred in 60% of the women with DV and in 5.7% of the women with PRES. Patients with DV had significantly increased bladder sensation, lower cystometric bladder capacity (CBC), lower bladder compliance, higher voiding detrusor pressure, smaller voided volume (VV), larger post-void residual volume (PVR), lower voiding efficiency (VE), and higher bladder outlet obstruction index (BOOI) than the women with PRES and the control individuals. Patients with PRES had significantly increased bladder sensation, lower CBC, lower maximum flow rate, smaller VV, larger PVR, and lower VE than the control individuals., Conclusions: DV and PRES were highly prevalent among the adult women with voiding dysfunction. Patients with DV had VUDS characteristics of BOO and urodynamic DO. The clinical symptoms of PRES were similar to those of DV, but the patients had low detrusor contractility and low DO rates., (© 2017 Wiley Periodicals, Inc.)

Aims: The aim of this study is to establish an optimized, minimally invasive transurethral catheterization cystometry (TUCC) and a novel urethral pressure profile (UPP) measurement for mice., Methods: The optimized TUCC and the UPP measurement were first established. This optimized TUCC was then performed in 16 anesthetized female mice and compared with the suprapubic catheterization cystometry (SCC) in parallel after suprapubic catheters implantation (SCI; on zero, third, and seventh day, respectively). Finally, the optimized TUCC and novel UPP measurement were applied to investigate in another eight mice of partial bladder outlet obstruction (pBOO) model. The urodynamic parameters including micturition pressure (MP), basal pressure (BP), threshold pressure (TP), bladder capacity (BC), micturition volume (MV), residual urine (RV), bladder compliance (COM), maximum urethral pressure (MUP), bladder pressure curve and UPP were recorded. Statistical cross-comparisons of parameters for two kinds of cystometries and pBOO model were performed., Results: Compared with the optimized TUCC before SCI, the MV, RV, BC, and MP decreased significantly on the seventh day after SCI (270.4-132.5 µL, 46.13-20.09 µL, 316.4-152.5 µL, 30.01-24.34 cmH 2 0, respectively). After SCI, the BP, MP, TP, MV, RV, BC, and COM showed no significant difference between the TUCC and SCC at the same time point. The MUP increased significantly after pBOO operation (19.1-46.6 cmH 2 0, P < 0.05)., Conclusions: The minimally invasive TUCC along with UPP measurement could be widely applied to study the bladder function of mice as a feasible, repeatable, and accessible method., (© 2017 Wiley Periodicals, Inc.)

Voiding dysfunction that results from bladder outlet (BO) obstruction is known to alter significantly the dynamics of urine passage through the urinary tract. To non-invasively image this phenomenon on a time-resolved basis, we pursued the first application of a recently developed flow visualization technique called vector projectile imaging (VPI) that can track the spatiotemporal dynamics of flow vector fields at a frame rate of 10,000 fps (based on plane wave excitation and least-squares Doppler vector estimation principles). For this investigation, we designed a new anthropomorphic urethral tract phantom to reconstruct urinary flow dynamics under controlled conditions (300 mm H 2 O inlet pressure and atmospheric outlet pressure). Both a normal model and a diseased model with BO obstruction were developed for experimentation. VPI cine loops were derived from these urinary flow phantoms. Results show that VPI is capable of depicting differences in the flow dynamics of normal and diseased urinary tracts. In the case with BO obstruction, VPI depicted the presence of BO flow jet and vortices in the prostatic urethra. The corresponding spatial-maximum flow velocity magnitude was estimated to be 2.43 m/s, and it is significantly faster than that for the normal model (1.52 m/s) and is in line with values derived from computational fluid dynamics simulations. Overall, this investigation demonstrates the feasibility of using vector flow visualization techniques to non-invasively examine internal flow characteristics related to voiding dysfunction in the urethral tract., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Context: Elderly men are an increasing proportion of the aging population in the 21st century. Urinary incontinence reduces the quality of life and increases the burden of care for the aging population., Objective: The primary objective of this review is to explore the etiopathology of common causes of incontinence in aging male patients. The focus is on the algorithm of the initial evaluation of these patients from both a primary care and a urologic standpoint., Evidence Acquisition: A nonsystematic review of the literature was performed in September 2017. The data and evidence of this paper have been obtained by a PubMed search, and through official statements and recommendations from the International Consultation on Incontinence. Our search incorporated terms such as elderly, urinary incontinence, male, urodynamics, bladder outlet obstruction, BPH, neurologic, urethral stricture, spinal shock, and urethral sphincter injury., Evidence Synthesis: A total of 7204 papers were identified; 6838 were excluded for female populations and populations <65 yr. A broad differential diagnosis exists for urinary incontinence in aging male patients, and many patients will be found to have multifactorial incontinence, compounding the issue. Neurologic etiologies common in this population include cerebrovascular accidents, Parkinson's disease, and dementia. Spinal cord injuries and multiple sclerosis are less common. In this analysis, non-neurologic etiologies leading to incontinence are broadly grouped under bladder outlet obstruction, sphincter injury, overactive bladder, underactive bladder, polypharmacy, and urinary tract infections., Conclusions: We provide a review of the differential diagnosis of incontinence in an elderly male patient. There is a need for understanding etiopathology and recognizing that many patients may have a combination of the above. The assessment algorithm, modified from the International Continence Society, provides a pathway for the provider in evaluating and treating elderly patients., Patient Summary: In this review, we have identified the sources of urinary incontinence in elderly male patients by neurologic and non-neurologic causes. We also discuss the basic evaluation and workup of an incontinent patient., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: This review examines current terminology used to define non-neurogenic chronic urinary retention (CUR), describes the pathophysiology of urinary retention, and highlights contemporary diagnostic and treatment algorithms., Recent Findings: There is no standardized definition for the condition, but volumes >300 ml are commonly used to describe CUR. It is a clinical diagnosis which does not require urodynamics. Pathophysiologic causes of CUR be from myogenic, neurogenic, bladder outlet obstruction, or a combination of these sources. Treatment algorithms recommend stratifying patients with chronic urinary retention by risk and by symptoms before initiating treatment. Common CUR outcome endpoints need to be better utilized so that treatment modalities can be compared. Non-neurogenic CUR is a heterogeneous condition that has multiple definitions, underlying physiologies, and possible endpoints. Standardization is needed to better understand and treat CUR.

We aimed to compare the short-term outcomes of men who had urodynamic evidence of detrusor underactivity (DU) or detrusor overactivity (DO) of a non-neurogenic etiology as well as bladder outlet obstruction (BOO) and who underwent Holmium Laser Enucleation of the prostate (HoLEP). A database of 322 patients who underwent HoLEP between 2010 and 2014 was analyzed. Patients were classified into three groups according to the results of a preoperative urodynamic study. Preoperative parameters such as International Prostate Symptom Score (IPSS), Quality of Life (QoL) index, IPSS grade, uroflowmetry were compared with postoperative parameters measured at 6 months. There were 138 patients with BOO-only and 89 patients with BOO and detrusor dysfunction including 56 with DO and 33 with DU. The degree of improvement in IPSS-total (BOO: 10.7, DO: 8.3, DU: 7.0; p = 0.023) was greater in the BOO-only group than in the DU group. There were more patients whose IPSS grade improved in the BOO-only group (71%) than in the detrusor dysfunction group (DO: 53.6% and DU: 45.5%). Postoperative IPSS-voiding (4.5 vs 7.0), and Qmax (18 vs 13.7) in the BOO-only group were significantly better than those in the DU group. Additionally, postoperative IPSS-storage (4.7 vs 6.7), and IPSS-total (9.1 vs 12.3) in the BOO-only group were significantly better than in the DO group (all p < 0.05). In conclusion, early surgical management for men with severe LUTS and associated BPH before secondary degeneration occurs may be beneficial for preserving detrusor function and yield better treatment outcomes., (Copyright © 2017. Published by Elsevier Taiwan.)

We investigated the characteristics of bladder mechanosensitive single-unit afferent activities (SAAs) in rats with a bladder outlet obstruction (BOO) and their relationship with bladder microcontractions. Male Wistar rats were divided into Sham and BOO groups. Four or 10 days after the surgery, rats were anesthetized with urethane. The SAAs of Aδ- or C-fibers from the L6 dorsal roots were recorded during bladder filling. The BOO group showed a higher number of microcontractions and lower SAAs of Aδ-fibers compared with those of the Sham group. These findings were significant at day 10 post-operatively. In contrast, SAAs of C-fibers were not significantly different between the groups at either day 4 or 10. In the BOO group at day 10, the SAAs of both Aδ- and C-fibers at the "ascending" phase of microcontractions were significantly higher than those at the other phases (descending or stationary), and a similar tendency was also observed at day 4. Taken together, during bladder filling, the bladder mechanosensitive SAAs of Aδ-fibers were attenuated, but SAAs of both Aδ- and C-fibers were intermittently enhanced by propagation of microcontractions.

Primary bladder neck obstruction (PBNO) represents an inappropriate or inadequate relaxation of the bladder neck during micturition. Based on the observation of an increased rate of postural imbalances in male patients with PBNO, we hypothesized a possible role of an unbalanced biomechanics of the pelvis on urethral sphincters activity. Our aim was to identify kinematic imbalances, usually disregarded in PBNO patients, and which could eventually be involved in the etiopathogenesis of the disease. Seven male adult patients (39.6±7.1years) were recruited; in all patients, PBNO was suspected at bladder diary and uroflowmetry, and was endoscopically confirmed with urethroscopy. Participants gait was recorded with a motion capture system (BTS Spa, Italy) to obtain three-dimensional joint angles and gait parameters. Multivariate statistics based on a Principal Component model allowed to assess the similarity of patients' gait patterns with respect to control subjects. The main finding is that patients with PBNO showed significant discordance in the observations at the ankle and pelvis level. Additionally, 6/7 patients demonstrated altered trunk positions compared to normal curves. We suggest that the identified postural imbalances could represent the cause for an anomalous activation of pelvic floor muscles (hypertonia). The consequent urinary sphincters hypercontraction may be responsible for the development of voiding dysfunction in male patients with no significant morphological alterations. Results reinforced the hypothesis of an etiopathogenetic role of postural imbalances on primary bladder neck obstruction in male patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO)., Methods: Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA., Results: Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups., Conclusions: Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS., (© 2016 Wiley Periodicals, Inc.)

BACKGROUND The abdominal straining pattern can act as a novel parameter for improving the prediction of bladder outlet obstruction (BOO). To preserve detrusor function in the early stage of urinary system impairment, such as BOO, we establish a novel method for cystometry and Intra-abdominal pressure (IAP) assessments in rodents without cystostomy. MATERIAL AND METHODS Twenty mice and rats were divided into three groups (control, sham-operated and BOO group) respectively. The cystometry and IAP assessments were measured by the pediatric venous indwelling sheath and coronary dilatation catheter connected to Laborie urodynamic system on postoperative day 7. Data was collected simultaneously through urethra and rectum in each group. In addition, bladder histology was assessed to confirm BOO. RESULTS The novel method can collect the urodynamic parameters successfully, including the BLPP, IAP, MBC, etc. IAP was elevated in BOO rats, but no significantly difference was found between the sham-operated rats and the control rats. The hypertrophy of detrusor muscle in bladder section was observed by Masson trichrome staining in BOO group compared with other groups. CONCLUSIONS Our novel method based on innovative research implement for cystometry and IAP assessments in rodents is a reliable and replicable approach for evaluating the lower urinary tract function. Especially it provides detailed information to evaluate lower urinary tract structures and function in the early stage of BOO.

Objectives: To evaluate the effect of naftopidil on bladder capillary blood flow using bladder outlet obstruction model rats., Methods: Female Sprague-Dawley rats were divided into three groups: control group, bladder-outlet-obstruction group, and bladder-outlet-obstruction + naftopidil group. Bladder-outlet-obstruction surgery was performed in the bladder-outlet-obstruction and bladder-outlet-obstruction + naftopidil groups. The control group received sham-operation. The bladder-outlet-obstruction + naftopidil group were treated with naftopidil (30 mg/kg) for 14 days after bladder-outlet-obstruction operation, while the control and bladder-outlet-obstruction groups were treated with vehicle. Continuous cystometry was performed 14 days after the surgery. Bladder blood flow was measured after 14 days using a pencil lens charge-coupled device microscopy system. The bladder was then harvested for histology and measuring 8-hydroxy-2'-deoxyguanosine tissue level by enzyme-linked immunosorbent assay., Results: In cystometry, the bladder-outlet-obstruction rats showed bladder overactivity, while naftopidil treatment improved the cystometric pattern. The blood flow through the submucosal capillaries of the bladder base in the bladder-outlet-obstruction group was lesser than that in the control, whereas the bladder-outlet-obstruction + naftopidil group showed significantly greater blood flow than the bladder-outlet-obstruction group. The bladder tissue in the bladder-outlet-obstruction group showed a tendency to contain more hypertrophic detrusor muscle and inflammatory cells compared to those in the control group, while naftopidil treatment suppressed these histological changes. The 8-hydroxy-2'-deoxyguanosine levels in the bladder tissue significantly differed among the three groups (the bladder-outlet-obstruction group > the bladder-outlet-obstruction + naftopidil group > the control group)., Conclusions: Naftopidil improved bladder overactivity as well as the impaired bladder blood flow.caused by bladder-outlet-obstruction., (© 2015 Wiley Publishing Asia Pty Ltd.)

Introduction: Primary female bladder neck obstruction is a rare clinical condition characterized by the absence/incomplete bladder neck opening during the voiding phase of micturition., Methods: We present the cases of two women complaining dysuria, abdominal straining and sensation of incomplete bladder emptying. Videourodynamic evaluation was fundamental for a correct diagnosis., Results: Videourodynamic evaluation showed a high detrusor pressure during emptying phase, partial use of abdominal strain, very low urine flow rate and significant postvoid residual; imaging showed a defect in the physiological funneling of the bladder neck, absent or incomplete. The first step therapy is represented by oral alpha-blockers and clean intermittent self-catheterization in case of high postvoid residual. Surgical operations, such as bladder neck incision and resection, represent the last option., Conclusions: In our experience, bladder neck obstruction is a rare condition in women and only a complete clinical evaluation associated with videourodynamic study can lead to an appropriate diagnosis and treatment.

Objective: Underactive bladder is frequently encountered in elderly patients. It may result from detrusor underactivity (DU) or low detrusor contractility due to a urethral sphincter inhibitory effect. This study analyzed the video-urodynamic study (VUDS) characteristics of patients with underactive bladder in a large cohort of men with lower urinary tract symptoms (LUTS)., Methods: Male patients with LUTS who had failed the initial treatment were consecutively enrolled. All patients underwent detailed urological investigations including prostate measurement, free uroflowmetry, post-void residual volume (PVR) measurement, cystoscopy and VUDS. The VUDS characteristics of the men with underactive bladder were analyzed and compared with those of men with bladder outlet obstruction and normal tracing., Results: A total of 1329 men who underwent VUDS were included in this retrospective analysis. After VUDS, the final diagnosis was DU in 165 patients, poor relaxation of external sphincter (PRES) in 525, bladder outlet obstruction in 501, and normal tracing in 138. VUDS findings in DU patients showed a slowly increased detrusor pressure, intermittent detrusor contractions, or early decline of detrusor contraction, resulting in a low maximum flow rate (Qmax), and large PVR. In comparison with the PRES groups, DU patients were older, had reduced bladder sensation, lower detrusor pressure (Pdet), lower Qmax, larger PVR volume, and lower voiding efficiency. Patients with urodynamic PRES also had low-pressure-low-flow tracings, but their bladder sensation was similar to that with normal tracing. DU patients with very low Pdet also had low detrusor tonicity, and more medical co-morbidities than the other groups did., Conclusion: Idiopathic underactive bladder in elderly men could be attributed to urodynamic DU and PRES. DU is associated with old age, reduced bladder sensation, low voiding efficiency, and medical co-morbidities.

The diagnosis of bladder outlet obstruction (BOO) in the male is dependent on measurements of pressure and flow made during urodynamic studies. The procedure of urodynamics and the indices used to delineate BOO are well standardized largely as a result of the work of the International Continence Society. The clinical utility of the diagnosis of BOO is however, less well defined and there are several shortcomings and gaps in the currently available medical literature. Consequently the International Consultation on Incontinence Research Society (ICI-RS) held a think tank session in 2015 entitled "Male bladder outlet obstruction: Time to re-evaluate the definition and reconsider our diagnostic pathway?" This manuscript details the discussions that took place within that think tank setting out the pros and cons of the current definition of BOO and exploring alternative clinical tests (alone or in combination) which may be useful in the future investigation of male patients with lower urinary tract symptoms. The think tank panel concluded that pressure-flow studies remain the diagnostic gold-standard for BOO although there is still a lack of high quality evidence. Newer, less invasive, investigations have shown promise in terms of diagnostic accuracy for BOO but similar criticisms can be levelled against these tests. Therefore, the think tank suggests further research with regard to these alternative indicators to determine their clinical utility., (© 2017 Wiley Periodicals, Inc.)

Objectives: Pressure flow studies are regarded as the gold standard for evaluating both bladder outlet obstruction and detrusor contractility, but none of the current methods for evaluating bladder contraction patterns are well validated. Impaired bladder contraction results in a lower peak Watts factor and poorly sustained detrusor contractions. From this viewpoint, the maximum Watts factor and its pattern should be considered separately. To examine detrusor contraction pattern in patients after radical prostatectomy by using multiple parameters., Methods: A total of 37 patients with clinically localized prostate cancer underwent both pre- and post-radical prostatectomy urodynamic evaluations. The examined urodynamic parameters included the maximum flow rate, post-void residual volume, detrusor pressure at maximum flow, maximum Watts factor and relative volume (maximum Watts factor). Some parameters were defined from the Watts factor curve throughout micturition. Relative volume (maximum Watts factor) was the relative bladder volume at the maximum Watts factor. A normal detrusor contractility pattern involves an increase in Watts factor at the initiation followed by further gradual increases until the end of micturition., Results: Maximum flow rate increased significantly after radical prostatectomy (pre: 13.0 ± 6.5, post: 17.3 ± 7.7 mL/min; P < 0.01), whereas detrusor pressure at maximum flow and post-void residual volume decreased significantly (pre: 49.6 ± 21.6 and 31.4 ± 18.2 cmH 2 O; post: 48.6 ± 66.1 and 10.1 ± 28.5 mL; P < 0.05). Maximum Watts factor did not change significantly after radical prostatectomy (pre: 10.5 ± 3.1 W/m 2 , post: 11.0 ± 3.2 W/m 2 ), but relative volume (maximum Watts factor) decreased significantly (pre: 0.48 ± 0.3, post: 0.20 ± 0.20; P < 0.001). Maximum Watts factor represents the maximum power of bladder contraction at a particular point in time, whereas relative volume (maximum Watts factor) can be used to detect changes in detrusor contraction pattern., Conclusions: Evaluation of relative volume (maximum Watts factor) confirms that radical prostatectomy restores the normal detrusor contractility pattern in prostate cancer patients., (© 2017 The Japanese Urological Association.)

Introduction: Detrusor underactivity (DU) is currently a topic that receives major attention within functional urology. Urologists are often confronted with men who present with voiding dysfunction without bladder outlet obstruction (BOO) or after desobstructive or neuromodulation treatment. Their impaired bladder emptying is suspected to be related to failure of detrusor contractile function. Earlier research indicated that patients with non-obstructive urinary retention (NOR), for example, detrusor underactivity (DU), have a lower success rate after sacral neuromodulation (SNM) compared to patients treated with SNM for storage dysfunction. However, predicting factors for treatment success in the NOR group have not yet been defined., Methods and Evidence: The aim of this study was to assess whether the use of the new BOO-contractility (Maastricht-Hannover) nomogram can identify and predict SNM non-responders. Our results in 18 men showed that only 20% of patients below the 10th percentile, but 86% of men between the 10 and 25th percentiles of the nomogram can be treated successfully with SNM. All successfully treated patients voided without needing self- catheterisation., Conclusions: This pilot study showed for the first time that SNM treatment response in male patients with impaired bladder emptying can be predicted with the BOO-contractility (Maastricht-Hannover) nomogram. Men below the 10th percentile are likely to be treatment non-responders, whereas the majority of men above the 10th percentile are responders. Neurourol. Urodynam. 36:808-810, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Aim: We investigated the effects of silodosin (selective α 1A -adrenoceptor antagonist) on erectile dysfunction (ED) in a rat model of bladder outlet obstruction., Methods: Adult male Sprague-Dawley rats (n = 32) were divided into four groups: (i) sham-operated control; (ii) silodosin-treated (sham) control (0.1 mg/kg/day); (iii) partial bladder outlet obstruction (PBOO); and (iv) silodosin-treated with PBOO. PBOO was induced by ligation of the urethra for 6 weeks. In vivo, erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure (MAP). Organ-bath studies were performed on corpus cavernosum (CC) strips. Penises were assessed at baseline for protein expression of neuronal nitric oxide synthase (nNOS) and Rho-associated protein kinase (ROCK2) by Western blot. Immunohistochemistry and Masson trichrome staining were performed for analysis of nNOS protein levels and tissue alterations., Results: The ratio of ICP/MAP was significantly decreased in obstructed rats (0.26 ± 0.043, P < 0.01) compared to sham-control rats (0.64 ± 0.10), which was restored by the treatment (0.59 ± 0.14, P < 0.01) compared with obstructed rats. Relaxation responses were significantly reduced in strips from the obstructed group. Silodosin restored nitrergic relaxant responses. nNOS expression in the obstructed group decreased, which was improved by treatment. The decreased smooth muscle/collagen ratio in the bladder obstructed group was reversed by the treatment., Conclusions: Silodosin improves erectile function in obstructed rats. Further clinical trials are needed to explore fully the potential benefits of silodosin in patients with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in association with ED. Neurourol. Urodynam. 36:597-603, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition., Materials and Methods: C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed., Results: BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses., Conclusion: It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS., (Copyright® by the International Brazilian Journal of Urology.)

Chronic urethral obstruction and the ensuing bladder wall remodeling can lead to diminished bladder smooth muscle (BSM) contractility and debilitating lower urinary tract symptoms. No effective pharmacotherapy exists to restore BSM contractile function. Neuropilin 2 (Nrp2) is a transmembrane protein that is highly expressed in BSM. Nrp2 deletion in mice leads to increased BSM contraction. We determined whether genetic ablation of Nrp2 could restore BSM contractility following obstruction. Partial bladder outlet obstruction (pBOO) was created by urethral occlusion in mice with either constitutive and ubiquitous, or inducible smooth muscle-specific deletion of Nrp2, and Nrp2-intact littermates. Mice without obstruction served as additional controls. Contractility was measured by isometric tension testing. Nrp2 deletion prior to pBOO increased force generation in BSM 4 weeks following surgery. Deletion of Nrp2 in mice already subjected to pBOO for 4 weeks showed increased contractility of tissues tested 6 weeks after surgery compared with nondeleted controls. Assessment of tissues from patients with urodynamically defined bladder outlet obstruction revealed reduced NRP2 levels in obstructed bladders with compensated compared with decompensated function, relative to asymptomatic controls. We conclude that downregulation of Nrp2 promotes BSM force generation. Neuropilin 2 may represent a novel target to restore contractility following obstruction., Competing Interests: The authors have declared that no conflict of interest exists.

Objectives: To evaluate dynamic 2-dimensional (2D) transperineal pelvic sonographic findings and urodynamic studies in women with lower urinary tract symptoms after midurethral sling placement., Methods: Transperineal pelvic sonography and urodynamic studies were reviewed from women with a midurethral sling and lower urinary tract symptoms. The shape and sonographic dynamic change of the sling from the rest position to the maximum Valsalva maneuver and back to rest were recorded. Patients were categorized into 3 groups: group I, at rest, the sling lies parallel to the urethral lumen, and during Valsalva, the sling becomes C shaped; group 2, both at rest and during Valsalva, the sling runs parallel to the urethral lumen; and group 3, at rest, the sling is C shaped, and during Valsalva, this curved shape is maintained. For analytical purposes group 3 was compared with groups 1 and 2. Multiple logistic regressions were used to evaluate the association between transperineal pelvic sonography and urodynamic studies., Results: Seventy-seven women were enrolled. The detrusor pressure at the maximum flow rate was significantly higher in group 3 than groups 1 and 2 (mean ± SD, 36 ± 16 versus 19 ± 11 mm H 2 O; P < .001). The odds of high detrusor pressure (>20 mm H 2 O) in group 3 was approximately 12 times the odds of those in groups 1 and 2. After adjusting for other variables using a multiple logistic regression analysis, a statistically significant association between group 3 and high detrusor pressure persisted (odds ratio, 29.7; 95% confidence interval, 2.949-299.6; P = .0040) persisted., Conclusions: Transperineal dynamic 2D sonography can help predict women with high-pressure voiding after midurethral sling placement and aid in the diagnosis of bladder outlet obstruction., (© 2016 by the American Institute of Ultrasound in Medicine.)

Bladder outlet obstruction (BOO) induces significant organ remodeling, leading to lower urinary tract symptoms accompanied by urodynamic changes in bladder function. Here, we report mRNA and miRNA transcriptome sequencing of bladder samples from human patients with different urodynamically defined states of BOO. Patients' miRNA and mRNA expression profiles correlated with urodynamic findings. Validation of RNA sequencing results in an independent patient cohort identified combinations of 3 mRNAs (NRXN3, BMP7, UPK1A) and 3 miRNAs (miR-103a-3p, miR-10a-5p, miR-199a-3p) sufficient to discriminate between bladder functional states. All BOO patients shared cytokine and immune response pathways, TGF-β and NO signaling pathways, and hypertrophic PI3K/AKT signaling pathways. AP-1 and NFkB were dominant transcription factors, and TNF-α was the top upstream regulator. Integrated miRNA-mRNA expression analysis identified pathways and molecules targeted by differentially expressed miRNAs. Molecular changes in BOO suggest an increasing involvement of miRNAs in the control of bladder function from the overactive to underactive/acontractile states., Competing Interests: The authors have declared that no conflict of interest exists.

Aims: To design a simple office-based method to evaluate characteristic parameters from free uroflowmetries (FF) or pressure flow studies (PFs). This method can be applied by any physician to any recording, for instance in the follow-up of women at risk of developing outflow obstruction over time after surgical interventions., Method: Using pressure-flow studies (PFs), a reliable evaluation of urethral obstruction (U) and detrusor contractility (k) parameters could be obtained from the maximum flow rate and detrusor pressure at maximum flow rate. Nomograms for these parameters were derived from theoretical computations using the VBN model. Then, to allow an evaluation of the real urethral obstruction, a protocol was designed incorporating FF data in the follow-up of women suspected of urethral obstruction., Results: Two nomograms were obtained: (1) A urethral obstruction nomogram allowing to define a Woman Obstruction Index (WOI = p det.Qmax - 0.5*Q max ) which has the same structure than the A-G number in men. (2) A detrusor contractility nomogram which was generalized to all initial bladder volumes. The curves were fitted by algebraic equations easily programmable on any handheld device., Conclusion: Using a mathematical model of micturition and data extracted from PFs, two nomograms on urethral obstruction and detrusor contractility were designed. This tool offers a rapid and practical method for the clinician to follow women at risk of obstruction over time. Its applications will be the purpose of further studies. Neurourol. Urodynam. 36:37-42, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: To assess the long-term impacts of bladder neck incision (BNI) on continence and ejaculatory function of adults who underwent concurrent posterior urethral valve (PUV) ablation and BNI during childhood., Materials and Methods: A retrospective chart review was performed to find all adult patients with relevant history. All patients had undergone BNI at 6 o'clock proximal to the verumontanum with caution to leave the adventitia and verumontanum untouched. Charts were reviewed and attempts were made to contact those ≥18 years old for follow-up. Patients were specifically evaluated for lower urinary tract symptoms and ejaculatory condition., Results: Among patients treated for PUV between 1998 and 2015 in our center, 21 were ≥18 years old at the time of assessment. Until February 2016, we were able to contact 18 patients, all of whom agreed to participate. Mean age was 21.1 ± 2.9 years with a mean follow-up of 12.5 ± 4.8 years. None of those contacted had incontinence or dry ejaculations. All considered their ejaculations normal and only one complained of weak ejaculations. Four of 5 patients who consented to perform a semen analysis had normal tests and 1 had low sperm count with abnormal motility., Conclusion: BNI is not associated with additional risk of incontinence and dry ejaculation in early adulthood and preserves antegrade ejaculation. Concomitant valve ablation with BNI may provide additional benefits in care of PUV children, especially those with prominent bladder neck and poor bladder function at presentation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Voiding dysfunction in adult men may be caused by bladder outlet obstruction (BOO) and/or detrusor underactivity (DU). Until now, it is only possible to classify BOO and DU by pressure-flow analysis. Low values of the maximum Watts factor (W max ) indicate DU but thresholds for the diagnosis have not been established. Purpose of this study was to construct a nomogram using bladder outlet resistance and detrusor contractility in order to classify BOO and DU simultaneously., Methods: Treatment naïve men aged ≥40 years with uncomplicated lower urinary tract symptoms (LUTS) were prospectively evaluated. Patients were assessed with IPSS, prostate volume, uroflowmetry, post-void residual, and pressure-flow measurement. The bladder outlet obstruction index (BOOI) was used to determine BOO-grade and W max to calculate detrusor contractility. Individual BOOI-W max values were plotted in a graph. Linear interpolation was applied to determine the 10th, 25th, 50th, 75th, and 90th percentiles., Results: Retrospective analysis of 822 male patients with means of 64 years, IPSS 16, and prostate volume of 40 cc. Patient and clinical parameters of the <25th percentile groups were significantly different compared to the 25th-50th percentiles: age (66 vs. 63 years, P = 0.006), bladder capacity (503 vs. 442 ml, P = 0.009), post-void residual urine (167 vs. 116 ml, P = 0.001), and voiding efficiency (67% vs. 73%, P = 0.015)., Conclusions: The nomogram quantifies the relationship between detrusor contractility and BOO in men with LUTS. A measurement value <25th percentile correlates with clinical indicators of DU and is proposed as a cut-off value for DU-diagnosis. Higher age, bladder capacity, and PVR as well as lower voiding efficiency indicate DU. Neurourol. Urodynam. 35:980-986, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: Though urodynamic study (UDS) is the current established standard to distinguish between detrusor underactivity (DU) and bladder outlet obstruction (BOO), concerns of patient discomfort and potential complications of catheterization deters its use. We inspected clinical variables to discriminate between DU and BOO in uroflowmetry, which can be more easily performed in clinical practice., Materials and Methods: Total 240 men who both underwent UDS and uroflowmetry were reviewed. The patients were divided into 2 groups by a single experienced urologist based on UDS outcome; DU (n=111) and BOO (n=129). From uroflowmetry, 5 variables including maximal flow rate (Qmax), average flow rate (Qave), voiding volume (VV), postvoid residual urine (PVR), and value of Qmax minus Qave (DeltaQ) was obtained. Multivariable analysis including receiver operating characteristic (ROC) curve analysis was performed to identify the important diagnostic predictors., Results: The mean age (±standard deviation) was 65.3±9.2 years. Except Qave, all uroflowmetry components were significantly different between DU and BOO groups. DeltaQ was smaller in DU group (8.71 mL/s vs. 5.26 mL/s, p<0.001). By logistic regression analysis, DeltaQ (Exp(B)=0.648, p<0.001) and PVR (Exp(B)=1.009, p<0.001) significantly discriminate DU and BOO diagnosis. In diagnosing DU using a single variable, the area under the curve of ROC from DeltaQ (0.806) was significantly higher than that from Qmax (0.763, p=0.0126) and Qave (0.574, p<0.0001)., Conclusions: Our findings suggest that DeltaQ is a novel predictor capable of discriminating DU from BOO in men with obstructive lower urinary tract symptom., Competing Interests: The authors have nothing to disclose.

Objectives: To evaluate whether urodynamic investigation (UDI), the gold standard to assess refractory lower urinary tract symptoms (LUTS), is appropriate to select healthy volunteers with apparent normal lower urinary tract function as control subjects for comparative studies., Subjects and Methods: 42 healthy subjects (22 women, mean age 32±10 years; 20 men, mean age 37±12 years) without LUTS were included into this prospective single-centre cohort study. All subjects recorded a 3-day bladder diary, completed validated questionnaires regarding LUTS, and underwent neuro-urological assessment as well as free uroflowmetry. Same session repeat UDI was performed according to "Good Urodynamic Practice" recommended by the International Continence Society, but using an air-charged instead of a water-filled catheter, and evaluated by a blinded investigator., Results: All 3-day bladder diaries, LUTS questionnaires, neuro-urological assessments and free uroflowmetries were within normal limits. Overall (either during the first or second UDI), same session repeat UDI revealed pathological findings in 71% (30/42): Detrusor overactivity was detected in 14% (3/22) and 30% (6/20), post void residual >100mL in 14% (3/22) and 25% (5/20), bladder outlet obstruction in 9% (2/22) and 20% (4/20) and detrusor sphincter dyssynergia in 77% (17/22) and 65% (13/20) of our women and men, respectively. Repeatability of detrusor overactivity (κ = 0.78, 95% CI: 0.54-1.02) and detrusor sphincter dyssynergia (κ = 0.77, 95% CI: 0.55-0.98) showed substantial agreement between both UDIs. All other assessed urodynamic parameters had wide 95% limits of agreement for differences in the parameters indicating poor repeatability., Conclusions: More than 70% of our healthy subjects showed pathological urodynamic findings. Although UDI is the gold standard to assess refractory LUTS, it seems not to be applicable in healthy subjects to define normal lower urinary tract function. Therefore, we do not recommend using UDI to select healthy control subjects., Competing Interests: The authors have declared that no competing interests exist.

The discovery of microRNAs (miRNAs), which are ~22 nucleotide RNAs that inhibit protein synthesis in a sequence-specific manner and are present in a range of species, has born hope of new therapeutic strategies. miRNAs play important roles in development and disease, but they remain poorly studied in uropathologies beyond cancer. Here, we discuss biological functions of miRNAs in the lower urogenital tract. A special focus is on miRNAs that change in bladder outlet obstruction (BOO). This is a condition that affects nearly one third of all men over 60 years and that involves growth and fibrosis of the urinary bladder. Animal models of BOO, such as that in rat, have been developed, and they feature a massive 6-fold bladder growth over 6 weeks. Using microarrays, we have charted the miRNAs that change during the time course of this process and identified several with important modulatory roles. We discuss known and predicted functions of miR-1, miR-29, miR-30, miR-132/212, miR-204 and miR-221, all of which change in BOO. The majority of the miRNA-mediated influences in BOO are expected to favour growth. We also outline evidence that miR-29 represents a key effector molecule in a generic response to mechanical distension that is designed to counteract exaggerated organ deformation via effects on matrix deposition and stiffness. We conclude that miRNAs play important roles in bladder remodelling and growth and that they may be targeted pharmacologically to combat diseases of the lower urinary tract., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: We investigated urothelial integrity, suburothelial inflammation and the expression of sensory proteins in the bladder urothelium of male patients with bladder outlet obstruction and various bladder dysfunctions., Materials and Methods: We prospectively enrolled 33 men with urodynamically proven bladder outlet obstruction as the study group. Bladder biopsies were obtained from all study patients and 10 control patients. The expression of E-cadherin, zonula occludens-1, tryptase, apoptosis, TRPV (transient receptor potential vanilloid) 1 and 4, β3 adrenoreceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible/epithelial nitric oxide synthase were compared between study and control patients., Results: Study patients had significantly lower expression of E-cadherin, and a higher number of suburothelial mast and apoptotic cells than controls. Additionally, higher expression of P2X3 and M2 muscarinic receptors, and lower expression of M3 muscarinic receptor were detected in study patients. The detrusor underactivity subgroup was characterized by significantly higher expression of β3 adrenoreceptors and lower expression of inducible nitric oxide synthase than in controls. In study patients a significantly positive correlation was noted between voided volume and E-cadherin expression (r = 0.372), volume at first sensation of filling and β3 adrenoreceptor expression (r = 0.386), and detrusor pressure and M2 muscarinic receptor expression (r = 0.496) in the bladder urothelium (each p <0.05)., Conclusions: Urothelial dysfunction, suburothelial inflammation, cellular apoptosis and alterations in sensory proteins are prominent in bladder dysfunction secondary to bladder outlet obstruction. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of bladder dysfunction and detrusor underactivity in patients with bladder outlet obstruction., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The diagnosis and evaluation of bladder outlet obstruction (BOO) in women remains a challenging topic. The goal of this study is to review recent literature and summarize the diagnosis and management of BOO with special focus on recent progress., Recent Findings: In recent years, numerous advances in the area of female BOO have taken place including a movement towards unified diagnostic criteria, summary of functional and anatomic causes, and exploration of potential diagnostic options., Summary: This review discusses the known diagnosis and management of female bladder outlet obstruction, yet highlights specific functional causes, new criteria available for diagnosis, and long-term results of treatment options.

Due to their paracrine action, leukotrienes released from the urothelium are involved in control of the bladder function. Anti-leukotriene agents appear to exert an ameliorating effect in bladder overactivity. It is unknown, whether their possible, modulatory impact on the autonomic nervous system (ANS) activity may also contribute to the potentially beneficial effect of those compounds. Therefore, our aim was to indirectly estimate the ANS function using the heart rate variability (HRV) study in rats with experimental partial bladder outlet obstruction (PBOO), reflecting human benign prostatic hyperplasia (BPH), treated with leukotriene receptor antagonist - montelukast (MLKT). Twenty rats with surgically induced PBOO lasting for 14 days, divided into two groups: group 1 (10 control subjects) and group 2 (10 MLKT-treated rats; 2 mg/rat/day) were subjected to HRV recordings, preceded by daily urine collection and a subsequent cystectomy with histopathological evaluation of collected bladders. Standard HRV time and spectral parameters were calculated. MLKT-treated animals demonstrated an increase in power of non-normalized LF (low frequency) and HF (high frequency) components with no change of the total HRV power. Moreover, an increase and decrease in normalized nLF and nHF, respectively, were assessed in those animals compared to the control. Additionally, a decrease in daily diuresis measurement was demonstrated in MLKT-treated animals. Montelukast treatment resulted in the functional ANS status re-arrangement, with sympathetic overdrive and parasympathetic withdrawal. Those changes may contribute to alleviation of bladder overactivity symptoms, independently on leukotriene receptors blockade.

Lower urinary tract symptoms (LUTS) are a group of voiding symptoms affecting both genders as they age. Traditionally, LUTS in men were commonly attributed to bladder outlet obstruction (BOO) due to benign prostatic enlargement (BPE). It was later shown that, in approximately one-third to more than one-half of cases, LUTS in men are not associated with BOO. Urodynamic changes in the male bladder and symptom scores in aging men were found to be identical to their age-matched female counterparts. These observations suggested that LUTS in the elderly do not necessarily relate to BOO and may result from local changes in bladder muscle, nerves, and blood vessels. However, aging factors predisposing to bladder dysfunction and LUTS remain unknown. Growing evidence suggests that aging-associated pelvic ischemia may be a primary factor in the development of nonobstructed nonneurogenic overactive bladder and LUTS. First identified in experimental models and later in clinical studies, pelvic ischemia has been shown to compromise the lower urinary tract structure and lead to dysfunction. Structural and functional consequences of bladder and prostate ischemia have been documented in animal models. Clinical studies have shown that bladder and prostate blood flow decreases with aging. The severity of LUTS in elderly patients correlates with the degrees of bladder ischemia. LUTS improvement with α blockers has been associated with increased bladder blood flow. Pelvic ischemia may be an independent factor in nonobstructed nonneurogenic bladder instability and LUTS. Further research into the pathophysiology of LUTS in pelvic ischemia may lead to better management of this problem in the elderly population.

A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- and α1B-AR through screening of an in-house compound library. From initial structure-activity relationship studies, we found lead compound 9m with hERG K(+) channel liability. To develop analogues with reduced hERG K(+) channel inhibition, a combination of site-directed mutagenesis and docking studies was employed. Further optimization led to the discovery of (R)-9s and 9u, which showed antagonistic activity by a bladder strip test in rats with bladder outlet obstruction, as well as ameliorated cystitis-induced urinary frequency in rats. Ultimately, 9u was selected as a clinical candidate. This is the first study to show the utility of iminopyridine derivatives as selective α1D-AR antagonists and evaluate their effects in vivo.

The non-specific symptoms the patients express upon the presentation of female bladder outlet obstruction make it a challenge to diagnose. There are subtle differences between the obstructed patient and those whose bladders are underactive and/or fail to mount a detrusor contraction. These disparities can be extracted through a thorough history and examination. At times, the clinician may utilize nomograms, non-invasive uroflow, and urodynamics with the addition of fluoroscopy to establish the diagnosis of obstruction. Management of the obstruction depends on the nature of the condition, whether functional or anatomical. The increase in the number of sling procedures performed to treat stress urinary incontinence has resulted in a rise in the number of iatrogenic obstructions. The temporal relationship between surgery and obstruction is the key to identifying the problem.

Aims: To investigate the effect of the phosphodiesterase 5 (PDE5) inhibitor Tadalafil on bladder blood flow and bladder function in a rat model of partial bladder outlet obstruction (BOO)., Methods: Female 14-15-week-old Sprague-Dawley rats were divided into three groups. BOO was surgically induced in rats by placing a rubber ring around the urethra. BOO rats were administered daily oral Tadalafil (BOO-Tadalafil) or vehicle (BOO-Vehicle), while sham-operated animals were treated with vehicle (Sham). On the 14th day after surgery, micturition behavior was recorded for 24 hr by using a metabolic cage. On the 15th day after surgery, bladder blood flow and bladder weight were measured. The expression of PDE5 mRNA in the vesical and iliac arteries of intact rats was measured by reverse transcriptase-polymerase chain reaction., Results: BOO led to a significant decrease in bladder blood flow and a significant increase in bladder weight. These changes were partially suppressed by Tadalafil treatment. The number of micturitions in the BOO group was significantly increased and the average micturition volume was significantly decreased, without affecting the total micturition volume. Repeated Tadalafil treatment markedly inhibited the increase in micturition frequency and the decrease in average micturition volume. PDE5 mRNA was expressed in the vesical and iliac arteries., Conclusion: Tadalafil suppressed the reduction in bladder blood flow caused by BOO in rats and improved urinary function. This action of Tadalafil may contribute to its amelioration of bladder function. Neurourol. Urodynam. 35:444-449, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: Posterior urethral valves are the most common cause of partial bladder outlet obstruction in the pediatric population. However, to our knowledge the etiology and the detailed mechanisms underlying pathological changes in the bladder following partial bladder outlet obstruction remain to be elucidated. Recent findings suggest that hypoxia and associated up-regulation of HIFs (hypoxia-inducible factors) have a key role in partial bladder outlet obstruction induced pathology in the bladder. We examined the effects of pharmacological inhibition of HIF pathways by 17-DMAG (17-(dimethylaminoethylamino)-17-demethoxygeldanamycin) in pathophysiological phenotypes after partial bladder outlet obstruction., Materials and Methods: Partial bladder outlet obstruction was surgically created in male C57BL/6J mice. The animals received oral administration of 17-DMAG or vehicle daily starting from the initiation of obstruction up to 5 days. Sham operated mice served as controls. Bladders were harvested from each group 2, 4 and 7 days postoperatively, and analyzed for histological and biochemical changes. Bladder function was assessed by in vitro muscle contractility recordings., Results: Partial bladder outlet obstruction caused a significant increase in the bladder mass accompanying enhanced collagen deposition in the bladder wall while 17-DMAG treatment suppressed those increases. Treatment with 17-DMAG attenuated the degree of up-regulation of HIFs and their target genes involving the development of tissue fibrosis in obstructed bladders. Treatment with 17-DMAG improved the decreased responses of obstructed bladder strips to electrical field stimulation and KCl., Conclusions: In vivo 17-DMAG treatment decreased partial bladder outlet obstruction induced pathophysiological changes in the bladder. HIF pathway inhibition has a potential clinical implication for the development of novel pharmacological therapies to treat bladder pathology associated with partial bladder outlet obstruction., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.

Objective: To investigate the clinical and urodynamic features of patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) according to their prostate size., Materials and Methods: We analyzed 2039 LUTS/BPH patients who underwent urodynamic study between October 2004 and August 2013. We divided the patients into three groups according to their prostate size: small (≤30 mL), moderately enlarged (31-80 mL), and large prostate (≥81 mL) groups. We compared the groups regarding age, International Prostatic Symptom Score, maximal flow rate (Qmax), postvoided residual (PVR), serum prostate-specific antigen, prostate volume measured by ultrasonography, and urodynamic findings., Results: Patients with a small prostate had better urodynamic outcomes than those with larger prostates in overall population. Although the total prostate volume significantly correlated with the bladder outlet obstruction (BOO) index (r  =  0.51), BOO patients with a small prostate had similar Qmax, higher PVR, and lower voiding efficiency, compared to those with larger prostates. Moreover, urodynamic parameters indicating bladder abnormalities, including low compliance and involuntary detrusor contraction positivity, were similar among the groups in BOO patients. A higher proportion of detrusor underactivity was also observed in the small prostate group in BOO patients. Finally, when adjusting for potential confounding variables, we identified serum prostate-specific antigen levels (odds ratio, 1.34) and Qmax (odds ratio, 0.77) as significant predictors for BOO in LUTS/BPH patients with a small prostate., Conclusion: BOO patients with a small prostate showed higher PVR and poor voiding efficiency, as well as similar urodynamic bladder abnormalities, compared to those with moderately enlarged and large prostates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: We investigated the relationship between IL-1β and morphological and functional changes following partial bladder outlet obstruction (pBOO)., Methods: Female wild-type C57/BL6 mice (WT) and IL-1β-/- mice (KO) were used. Animals were sacrificed either 1 or 3 weeks after pBOO or sham surgery, and their bladders were harvested to determine bladder weight, for RT-PCR to measure interleukin-1β (IL-1β), insulin growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β) levels, and for histological analysis with Hematoxylin-Eosin (HE) staining. Cystometry was performed on conscious animals 3 weeks after surgery to evaluate urodynamic parameters. IGF-1 was also administered intraperitoneally to KO with pBOO, and bladder weight was then investigated., Results: IL-1β-mRNA levels were significantly higher in WT-pBOO than in WT-sham. IGF-1-mRNA and TGF-β-mRNA levels were also significantly higher in WT-pBOO than in WT-sham; however, these increases were smaller in KO-pBOO than in WT-pBOO. Bladder weight was significantly higher in WT-pBOO than in WT-sham, while increases in bladder weight were significantly suppressed in KO-pBOO. HE staining revealed the thickened bladder wall in WT-pBOO, and this phenomenon was less in KO-pBOO than in WT-pBOO. Regarding the urodynamic parameters examined, micturition pressure and bladder capacity were significantly higher in WT-pBOO than in WT-sham, but remained unchanged in KO-pBOO. The administration of IGF-1 to KO-pBOO led to similar increases in bladder weight and the thickened bladder wall as those observed in WT-pBOO., Conclusion: IL-1β has the potential to induce bladder remodeling and deteriorate urodynamic parameters in pBOO., (© 2015 Wiley Periodicals, Inc.)

Aims: At present, existing bladder outlet obstruction (BOO) nomograms for women are still not universally accepted. Moreover, only limited information is available regarding bladder contractility in women. The aim is to present the discussions and recommendations from the think tank session "Can we construct and validate contractility and obstruction nomograms for women?" held at the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK., Methods: An overview of clinical significance, bladder mechanics and modelling, lack of existing nomograms for women, and development of new nomograms were presented and discussed in a multidisciplinary think tank session. This think tank session was based on a collaboration between physicians, engineers, and researchers and consensus was achieved on future research initiatives., Results and Conclusions: Based on the think tank discussion, the ICI-RS panel put forward the following recommendations: the need to acquire normative age-matched data in women to define "normal" and "pathological" values of urodynamic parameters; the inclusion of additional clinical data in new nomograms and the use of this extra dimension to develop clinically applicable nomograms for female BOO and contractility; and finally, the need to take into account the variability of BOO in women when developing female bladder contractility nomograms., (© 2016 Wiley Periodicals, Inc.)

Purpose: We report continence, upper tract changes, and augmentation indications and rates in consecutive patients undergoing bladder outlet surgery without augmentation for neurogenic urinary incontinence., Methods: From 2000 to 2007, 37 patients underwent bladder neck sling (BNS), and from 2007 to 2013, 45 patients had Leadbetter/Mitchell bladder neck revision plus sling (LMS), all without augmentation. Mitrofanoff channels were created in all cases. Twenty children with persistent outlet insufficiency underwent bladder neck closure (BNC). All patients had pre- and postoperative urodynamic testing (UD)., Results: Mean follow-up was 60 months after BNS, 38 months after LMS, and 29 months after BNC. Continence (dry, no pads) was achieved significantly more often with LMS versus BNS (66% vs. 37%). There were no significant differences between these patients in preoperative UD % capacity, end filling pressure (EFP), or compliance. Those that became dry had a greater % capacity on postoperative UD, but postoperative EFP was similar between dry and wet LMS and BNS patients. BNC resulted in dryness in 65% of patients, with most incontinence occurring from the Mitrofanoff stoma associated with filling pressures > 40 cm. A total of 10 (12%) children had augmentation, seven after BNC. Clinical indications were end filling pressures > 40 cm plus hydronephrosis ≥ grade 3, and/or persistent incontinence. Need for augmentation was not predicted by preoperative urodynamic parameters. Postoperative UD in those who were augmented showed significantly less % capacity and compliance, and significantly greater EFP, than those not augmented., Conclusions: Dryness was achieved in only 33% of BNS versus 66% of LMS and BNC patients. Twelve percent of consecutive children undergoing bladder outlet surgery for neurogenic incontinence developed clinical parameters leading to augmentation. These occurred most often after BNC., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The clinical diagnosis of detrusor underactivity (DU) is hampered by the need for invasive pressure flow studies (PFS) in combination with a lack of knowledge of the associated signs and symptoms. This has contributed to a lack of awareness of DU and underactive bladder, and to the assumption that symptoms are always due to bladder outlet obstruction (BOO)., Objective: To investigate the signs and symptoms recorded in a large urodynamic database of patients who met the diagnoses of DU, BOO, and normal, to identify the clinical features associated with DU., Design, Setting, and Participants: From the database of 28282 adult PFS records, 1788 patients were classified into: (1) those with DU without BOO; (2) those with BOO without DU; and (3) those with normal PFS., Results: Patients with DU reported a statistically significantly higher occurrence of decreased and/or interrupted urinary stream, hesitancy, feeling of incomplete bladder emptying, palpable bladder, and absent and/or decreased sensation compared with patients with normal PFS. Other differences were found between men with DU and BOO, and between women with DU and normal PFS., Conclusions: There are signs and symptoms that can distinguish DU patients from patients with normal PFS and further distinguish between DU and BOO, which is traditionally invasively diagnosed. This is a first step to better understand the clinical presentation of DU patients, is consistent with the recent underactive bladder working definition, and justifies further exploration of the signs and symptoms of DU., Patient Summary: The clinical diagnosis of detrusor underactivity is hampered by the need for invasive urodynamics in combination with a lack of knowledge of the associated signs and symptoms. This study has shown that there are signs and symptoms that can distinguish men and women patients with DU from patients with either normal urodynamic studies or with BOO., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)