Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF-ß and Wnt-ß catenin signaling pathways.

AIMS: Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre-clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue. METHODS: New Zealand White female rabbits (n = 6 each; young 6-12 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid-urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (ß-catenin which is an important mediator of Wnt signaling, Collagen-1, and TGF-ß) and atrophy (MuRF-1). RESULTS: Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age-related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid-urethral tissues. CONCLUSIONS: Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.

Refractory urgency urinary incontinence treatment in women: impact of age on outcomes and complications.

BACKGROUND: Women with refractory urgency urinary incontinence (ie, unresponsive to behavioral and pharmacological interventions) are treated with onabotulinumtoxinA or sacral neuromodulation. OBJECTIVE: The objective of the study was to compare treatment efficacy and adverse events in women <65 and ≥65 years old treated with onabotulinumtoxinA or sacral neuromodulation. STUDY DESIGN: This study was a planned secondary analysis of a multicenter, randomized trial that enrolled community-dwelling women with refractory urgency urinary incontinence to onabotulinumtoxinA or sacral neuromodulation treatments. The primary outcome was a change in mean daily urgency urinary incontinence episodes on a bladder diary over 6 months. Secondary outcomes included ≥75% urgency urinary incontinence episode reduction, change in symptom severity/quality of life, treatment satisfaction, and treatment-related adverse events. RESULTS: Both age groups experienced improvement in mean urgency urinary incontinence episodes per day following each treatment. There was no evidence that mean daily urgency urinary incontinence episode reduction differed between age groups for onabotulinumtoxinA (adjusted coefficient, -0.127, 95% confidence interval, -1.233 to 0.979; P = .821) or sacral neuromodulation (adjusted coefficient, -0.698, 95% confidence interval, -1.832 to 0.437; P = .227). Among those treated with onabotulinumtoxinA, women <65 years had 3.3-fold greater odds of ≥75% resolution than women ≥65 years (95% confidence interval, 1.56 -7.02). Women <65 years had a greater reduction in Overactive Bladder Questionnaire Short Form symptom bother scores compared with women ≥65 years by 7.49 points (95% confidence interval, -3.23 to -11.74), regardless of treatment group. There was no difference between quality of life improvement by age. Women ≥65 years had more urinary tract infections following onabotulinumtoxinA and sacral neuromodulation (odds ratio, 1.9, 95% confidence interval, 1.2-3.3). There was no evidence of age differences in sacral neuromodulation revision/removal or catheterization following onabotulinumtoxinA treatment. CONCLUSION: Younger women experienced greater absolute continence, symptom improvement, and fewer urinary tract infections; both older and younger women had beneficial urgency urinary incontinence episode reduction, similar rates of other treatment adverse events, and improved quality of life.

Surgical Treatment of Female Stress Urinary Incontinence: AUA/SUFU Guideline.

PURPOSE: Stress urinary incontinence is a common problem experienced by many women that can have a significant negative impact on the quality of life of those who suffer from the condition and potentially those friends and family members whose lives and activities may also be limited. MATERIALS AND METHODS: A comprehensive search of the literature was performed by ECRI Institute. This search included articles published between January 2005 and December 2015 with an updated abstract search conducted through September 2016. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: The AUA (American Urological Association) and SUFU (Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction) have formulated an evidence-based guideline focused on the surgical treatment of female stress urinary incontinence in both index and non-index patients. CONCLUSIONS: The surgical options for the treatment of stress urinary incontinence continue to evolve; as such, this guideline and the associated algorithm aim to outline the currently available treatment techniques as well as the data associated with each treatment. Indeed, the Panel recognizes that this guideline will require continued literature review and updating as further knowledge regarding current and future options continues to grow.

Urinary Biomarkers in Women with Refractory Urgency Urinary Incontinence Randomized to Sacral Neuromodulation versus OnabotulinumtoxinA Compared to Controls.

PURPOSE: We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes. MATERIALS AND METHODS: First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ≤0.01 and p ≤0.004 represented moderate evidence of an association with outcomes. RESULTS: Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother. CONCLUSIONS: Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.

Best practice policy statement on urodynamic antibiotic prophylaxis in the non-index patient.

AIMS: Antibiotic prophylaxis before urodynamic testing (UDS) is widely utilized to prevent urinary tract infection (UTI) with only limited guidance. The Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU) convened a Best Practice Policy Panel to formulate recommendations on the urodynamic antibiotic prophylaxis in the non-index patient. METHODS: Recommendations are based on a literature review and the Panel's expert opinion, with all recommendations graded using the Oxford grading system. RESULTS: All patients should be screened for symptoms of UTI and undergo dipstick urinalysis. If the clinician suspects a UTI, the UDS should be postponed until it has been treated. The first choice for prophylaxis is a single oral dose of trimethoprim-sulfamethoxazole before UDS, with alternative antibiotics chosen in case of allergy or intolerance. Individuals who do NOT require routine antibiotic prophylaxis include those without known relevant genitourinary anomalies, diabetics, those with prior genitourinary surgery, a history of recurrent UTI, post-menopausal women, recently hospitalized patients, patients with cardiac valvular disease, nutritional deficiencies or obesity. Identified risk factors that increase the potential for UTI following UDS and for which the panel recommends peri-procedure antibiotics include: known relevant neurogenic lower urinary tract dysfunction, elevated PVR, asymptomatic bacteriuria, immunosuppression, age over 70, and patients with any indwelling catheter, external urinary collection device, or performing intermittent catheterization. Patients with orthopedic implants have a separate risk stratification. CONCLUSIONS: These recommendations can assist urodynamic providers in the appropriate use of antibiotics for UDS testing. Clinical judgment of the provider must always be considered.

Urinary Incontinence in Women: A Review.

IMPORTANCE: Urinary incontinence, the involuntary loss of urine, is a common health condition that may decrease quality of life. Ten to twenty percent of women and up to 77% of women residing in nursing homes have urinary incontinence, yet only 25% seek or receive treatment. OBSERVATIONS: This review summarizes the evaluation and therapeutic options for women affected by urinary incontinence. The initial assessment should focus on understanding the effect of incontinence on quality of life, the patient's goals and preferences for treatment, the results of previous treatments, and the presence of concomitant conditions, such as advanced pelvic organ prolapse, that may require referral. Infection and hematuria need to be ruled out. In the absence of urinary infection or serious underlying pathology (such as cancer or serious neurologic disease) associated with urinary incontinence, the clinician should initiate unsupervised pelvic muscle exercises and lifestyle modifications appropriate to the patient to reduce her symptoms. These recommendations can include weight loss, adequate hydration, avoidance of excessive fluids, and regular voiding intervals that reduce urgency incontinence episodes. Urgency incontinence medications, with timely reassessment of symptoms, can be started without extensive evaluation. Specialist treatments for urgency incontinence include onabotulinumtoxinA and percutaneous or implanted neuromodulators. Stress incontinence surgery, the midurethral sling, is associated with symptom improvement in 48% to 90% of women and has low rates of mesh complications (<5%). CONCLUSIONS AND RELEVANCE: Urinary incontinence is common in women, although few seek care despite many effective treatment options. Clinicians should prioritize urinary incontinence detection, identify and treat modifiable factors, incorporate patient preference into evaluation and treatment, initiate conservative and medical therapy, and refer to specialists when underlying pathology is identified or conservative measures are ineffective.

A randomized trial of urodynamic testing before stress-incontinence surgery.

BACKGROUND: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes. METHODS: We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points. RESULTS: A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes. CONCLUSIONS: For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).

5-year longitudinal followup after retropubic and transobturator mid urethral slings.

PURPOSE: Few studies have characterized longer-term outcomes after retropubic and transobturator mid urethral slings. MATERIALS AND METHODS: Women completing 2-year participation in a randomized equivalence trial who had not undergone surgical re-treatment for stress urinary incontinence were invited to participate in a 5-year observational cohort. The primary outcome, treatment success, was defined as no re-treatment or self-reported stress incontinence symptoms. Secondary outcomes included urinary symptoms and quality of life, satisfaction, sexual function and adverse events. RESULTS: Of 597 women 404 (68%) from the original trial enrolled in the study. Five years after surgical treatment success was 7.9% greater in women assigned to the retropubic sling compared to the transobturator sling (51.3% vs 43.4%, 95% CI -1.4, 17.2), not meeting prespecified criteria for equivalence. Satisfaction decreased during 5 years but remained high and similar between arms (retropubic sling 79% vs transobturator sling 85%, p=0.15). Urinary symptoms and quality of life worsened with time (p <0.001), and women with a retropubic sling reported greater urinary urgency (p=0.001), more negative impact on quality of life (p=0.02) and worse sexual function (p=0.001). There was no difference in the proportion of women experiencing at least 1 adverse event (p=0.17). Seven new mesh erosions were noted (retropubic sling 3, transobturator sling 4). CONCLUSIONS: Treatment success decreased during 5 years for retropubic and transobturator slings, and did not meet the prespecified criteria for equivalence with retropubic demonstrating a slight benefit. However, satisfaction remained high in both arms. Women undergoing a transobturator sling procedure reported more sustained improvement in urinary symptoms and sexual function. New mesh erosions occurred in both arms over time, although at a similarly low rate.

Comparison of flowrates and voided volumes during non-instrumented uroflowmetry and pressure-flow studies in women with stress incontinence.

AIMS: The Blaivas-Groutz nomogram defines voiding obstruction in women using Qmax from the NIF and the maximum detrusor pressure (Pdetmax ) from the PFS. The aim of this study was to understand the relationship between NIF and PFS maximum flow rates in women with stress incontinence. METHODS: We analyzed the UDS of 597 women with stress-dominant urinary incontinence. Each subject underwent a NIF and then a PFS. Mixed model was used to test the hypothesis that the relationship between flow rates and voided volume (VV) were similar for NIF and PFS. RESULTS: There were 452 subjects with both NIF and PFS studies that met the inclusion criteria and had max flow rate (Qmax ) for both NIF and PFS. The mean age was 53. Overall, higher VV were observed during PFS compared to NIF and subjects had higher Qmax with NIF compared to PFS. The relationship between Qmax and VV was significantly different between NIF and PFS (P < 0.004). At 200 ml, NIF Qmax was 14% higher than PFS Qmax and this difference increased to 30% at 700 ml. CONCLUSION: The difference between PFS Qmax and NIF Qmax increases as VV increase. As a result, values from PFS and NIF cannot be used interchangeably as has been suggested in the Blaivas-Groutz nomogram for obstruction in women.

Retropubic versus transobturator midurethral slings for stress incontinence.

BACKGROUND: Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. METHODS: We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points. RESULTS: A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P=0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P=0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life. CONCLUSIONS: The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.)

Treatment success of retropubic and transobturator mid urethral slings at 24 months.

PURPOSE: Longer term comparative efficacy information regarding transobturator and retropubic mid urethral slings is needed. We report 24-month continence rates, complications and symptom outcomes from a randomized equivalence trial. MATERIALS AND METHODS: Primary outcomes were objective (negative stress test, negative pad test and no re-treatment for stress urinary incontinence) and subjective (no self-report of stress urinary incontinence symptoms, no leakage episodes on 3-day bladder diary and no re-treatment for stress urinary incontinence) success at 24 months. The predetermined equivalence margin was ± 12%. RESULTS: Of 597 randomized participants 516 (86.4%) were assessed. Objective success rates for retropubic and transobturator mid urethral slings were 77.3% and 72.3%, respectively (95% CI for difference of 5.1% was -2.0, 12.1), and subjective success rates were 55.7% and 48.3%, respectively (CI for difference of 7.4% was -0.7, 15.5). Neither objective nor subjective success rates met the prespecified criteria for equivalence. Patient satisfaction (retropubic 86.3% vs transobturator 88.1%, p = 0.58), frequency of de novo urgency incontinence (retropubic 0% vs transobturator 0.3%, p = 0.99) and occurrence of mesh exposure (retropubic 4.4% vs transobturator 2.7%, p = 0.26) were not significantly different. The retropubic mid urethral sling group had higher rates of voiding dysfunction requiring surgery (3.0% vs 0%, p = 0.002) and urinary tract infections (17.1% vs 10.7%, p = 0.025), whereas the transobturator group had more neurological symptoms (9.7% vs 5.4%, p = 0.045). CONCLUSIONS: Objective success rates met the criteria for equivalence at 12 months but no longer met these criteria at 24 months. Subjective success rates remained inconclusive for equivalence. Patient satisfaction remained high and symptom severity remained markedly improved. Continued surveillance is important in women undergoing mid urethral sling surgery.

Patient related factors associated with long-term urinary continence after Burch colposuspension and pubovaginal fascial sling surgeries.

PURPOSE: We examined preoperative and postoperative patient related factors associated with continence status up to 7 years after surgery for stress urinary incontinence. MATERIALS AND METHODS: Women randomized to Burch colposuspension or fascial sling surgery and assessed for the primary outcome of urinary continence 2 years after surgery were eligible to enroll in a prospective observational study. Survival analysis was used to investigate baseline and postoperative factors in the subsequent risk of stress urinary incontinence, defined as self-report of stress urinary incontinence symptoms, incontinence episodes on a 3-day diary or surgical re-treatment. RESULTS: Of the women who participated in the randomized trial 74% (482 of 655) were enrolled in the followup study. Urinary continence rates decreased during a period of 2 to 7 years postoperatively from 42% to 13% in the Burch group and from 52% to 27% in the sling group, respectively. Among the baseline factors included in the first multivariable model age (p = 0.03), prior stress urinary incontinence surgery (p = 0.02), menopausal status (0.005), urge index (0.006), assigned surgery (p = 0.01) and recruiting site (p = 0.02) were independently associated with increased risk of incontinence. In the final multivariable model including baseline and postoperative factors, Burch surgery (p = 0.01), baseline variables of prior urinary incontinence surgery (p = 0.04), menopausal status (p = 0.03) and postoperative urge index (p <0.001) were each significantly associated with a greater risk of recurrent urinary incontinence. CONCLUSIONS: Preoperative and postoperative urgency incontinence symptoms, Burch urethropexy, prior stress urinary incontinence surgery and menopausal status were negatively associated with long-term continence rates. More effective treatment of urgency urinary incontinence in patients who undergo stress urinary incontinence surgery may improve long-term overall continence status.

Adverse events over two years after retropubic or transobturator midurethral sling surgery: findings from the Trial of Midurethral Slings (TOMUS) study.

OBJECTIVE: To describe surgical complications in 597 women over a 24-month period after randomization to retropubic or transobturator midurethral slings. STUDY DESIGN: During the Trial of Midurethral Slings study, the Data Safety Monitoring Board regularly reviewed summary reports of all adverse events using the Dindo Surgical Complication Scale. Logistic regression models were created to explore associations between clinicodemographic factors and surgical complications. RESULTS: A total of 383 adverse events were observed among 253 of the 597 women (42%). Seventy-five adverse events (20%) were classified as serious (serious adverse events); occurring in 70 women. Intraoperative bladder perforation (15 events) occurred exclusively in the retropubic group. Neurologic adverse events were more common in the transobturator group than in retropubic (32 events vs 20 events, respectively). Twenty-three (4%) women experienced mesh complications, including delayed presentations, in both groups. CONCLUSION: Adverse events vary by procedure, but are common after midurethral sling. Most events resolve without significant sequelae.

Prostate laser vaporization in men with urinary retention.

OBJECTIVE: • To evaluate the safety and efficacy of laser vaporization of the prostate (LVP) with several different wavelengths for urinary retention. PATIENTS AND METHODS: • A cohort study of patients undergoing LVP from 2005 to 2009 at a single institution was performed. • Outcomes were compared in those patients with urinary retention versus those without, using t-tests, Mann-Whitney U-test, chi-squared test and Fisher's exact test as appropriate. RESULTS: • During the study period, 122 patients underwent LVP, of which 39 (32%) presented with refractory urinary retention requiring indwelling or intermittent catheterization. • The mean ± SD period of postoperative follow-up was 11.2 ± 9.6 months. Comparing patients with and without urinary retention, there were no significant preoperative differences in median body mass index (25.6 versus 26.4 kg/m(2) ; P= 0.40) or prostate-specific antigen (2.3 versus 2 ng/mL; P= 0.27). • Patients with urinary retention were significantly more likely to be diabetic (33% versus 12%; P= 0.01), have heart disease (36% versus 15%; P= 0.01) and be taking anticoagulants (61% versus 31%; P= 0.003). • Following LVP, retention patients were more likely than non-retention patients to fail an initial voiding trial (28.2% versus 7.2%; P= 0.002). • In total, 36 of 39 (92%) retention patients no longer required catheterization after postoperative recovery. No patients required perioperative transfusion. • Compared to those without preoperative retention, retention patients had a longer median duration of postoperative catheterization (3 versus 1 days; P= 0.01). • There were similar rates of low- and high-grade complications (P= 0.275 and 1.000, respectively) and no significant difference in median hospital stay (1 versus 0 days; P= 0.212). CONCLUSIONS: • In the present study cohort, LVP was an effective and safe therapy for urinary retention. • Compared to patients without retention, those with retention had a higher prevalence of heart disease, diabetes and anticoagulant use. • Because the morbidity of LVP is low, and the prevalence of co-morbid disease high, LVP should be considered for the surgical management of refractory urinary retention.

Repeated Low-Dose Acrolein Triggers Irreversible Lamina Propria Edema in Urinary Bladder, Transient Voiding Behavior and Widening of Eyes to Mechanical Stimuli.

Acrolein is a metabolite of cyclophosphamide (CYP), an alkylating agent used for a wide range of benign and malignant diseases. CYP treatments are known to trigger hemorrhagic cystitis in patients and animals. Significant effort has been made to prevent CYP/acrolein-induced cystitis, while still maintaining its therapeutic benefits. As a result, supplementary therapeutic options to mediate the protective role against CYP/acrolein and lower doses of CYP are currently given to targeted patients, as compared to past treatments. There is still a need to further study the effects of the repeated low-dose CYP/acrolein on the pathophysiology of the urinary bladder. In our study, a one-time treatment of acrolein and repeated low-dose acrolein triggered the thickening of the smooth muscle and lamina propria in the urinary bladder of C57BL/6J mice, respectively. The first dose of acrolein did not trigger voiding dysfunction, but the second dose triggered high-volume low-frequency voiding. Interestingly, our new scoring criteria and concurrent behavioral assessment revealed that mice with repeated low-dose acrolein had a wider opening of eyes in response to mechanical stimuli. Our study suggests that clinical symptoms among patients undergoing prolonged low-dose CYP may differ from previously reported symptoms of CYP-induced hemorrhagic cystitis.

Evaluation of Age- and Radical-Prostatectomy Related Changes in Male Pelvic Floor Anatomy Based on Magnetic Resonance Imaging and 3-Dimensional Reconstruction.

PURPOSE: Puborectalis muscles (PRM) and ischiocavernosus muscles (ICM) play important roles in urinary continence and male erectile functions. Understanding of anatomy and surgical-injury related changes to these muscles is critical to monitor changes in continence or erectile function. Anatomical description of these muscles has undergone revisions because these conclusions were derived from cadavers. Our objectives were to: (i) elucidate male pelvic muscles by in-vivo magnetic resonance imaging (MRI) and 3-dimensional (3-D) reconstruction of these images and (ii) compare PRM and ICM thickness in healthy volunteers and symptomatic patients. MATERIALS AND METHODS: Healthy young male (mean age, 25 years; n=5), older male (age, 65-70 years; n=5), and post-prostatectomy patients with erectile dysfunction and urinary incontinence (age, 65-70 years; n=5) were scanned on a 3T-magnetic resonance scanner. Images were acquired from slices above urinary bladder base to urethra entry into penis. Pelvic bone, bladder/urethra, corpus cavernosum, ICM, PRM, and prostate were segmented. 3-D models of each structure were generated and assembled into composite images, and ICM and PRM thicknesses were calculated. RESULTS: We successfully reconstructed 3-D male pelvic floor anatomy including ICM, PRM, bladder, urethra, bulbospongiosus, corpus cavernosa, prostate and bones from the two groups. We documented significant reduction in PRM and ICM thickness in older men. CONCLUSIONS: This is perhaps the first 3-D reconstruction of male pelvic floor structures based on in-vivo MRI in healthy and symptomatic patients. Observed reduction in PRM and ICM thickness is possibly due to age-related atrophy.

Burch colposuspension versus fascial sling to reduce urinary stress incontinence.

BACKGROUND: Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations. METHODS: We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility. The primary outcomes were success in terms of overall urinary-incontinence measures, which required a negative pad test, no urinary incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress test, no self-reported symptoms, and no retreatment for the condition, and success in terms of measures of stress incontinence specifically, which required only the latter three criteria. We also assessed postoperative urge incontinence, voiding dysfunction, and adverse events. RESULTS: A total of 655 women were randomly assigned to study groups: 326 to undergo the sling procedure and 329 to undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty voiding, and postoperative urge incontinence. CONCLUSIONS: The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662 [ClinicalTrials.gov] .).

Urodynamic standardization in a large-scale, multicenter clinical trial examining the effects of daily tadalafil in men with lower urinary tract symptoms with or without benign prostatic obstruction.

AIMS: To present the methodology, standardization techniques, and results from post hoc test-retest reproducibility analyses for a large, placebo-controlled, multicenter trial, employing urodynamic studies (UDS) to assess the impact of daily tadalafil on men with lower urinary tract symptoms (LUTS) with or without benign prostatic obstruction (BPO). METHODS: UDS implemented International Continence Society (ICS) Good Urodynamic Practice guidelines and standardized urodynamic and LUTS terminology. Further standardization procedures included: equipment calibration; a detailed procedure manual and centralized training; and implementation of a central reader. Measures included: monitoring of invalid studies, comparison of actual versus expected standard deviation (SD) for primary outcome (detrusor pressure at maximum urinary flow rate [p(detQmax)]), and test-retest reproducibility of the placebo arm at baseline and endpoint. RESULTS: Two hundred men with moderate to severe LUTS (baseline IPSS >or=13) at 20 sites were randomized to receive either tadalafil 20 mg or placebo. All men underwent non-invasive uroflow and pressure-flow studies. Numbers of invalid studies at baseline and endpoint were 9.3% and 0.6%, respectively. Variability of p(detQmax) was lower than anticipated based on actual versus expected SD of 15 and 30, respectively. Correlation coefficients were very good for pressure-flow parameters including p(detQmax) (r = .83). CONCLUSIONS: Multicenter clinical trials using urodynamic outcomes require additional standardized procedures to limit inter-site variability. By implementing centralized training with a detailed procedure manual and use of a central reader, we were able to limit common difficulties arising in multicenter clinical trials, as well as demonstrate good test-retest reproducibility of pressure flow measures.

Complications in women undergoing Burch colposuspension versus autologous rectus fascial sling for stress urinary incontinence.

PURPOSE: We determined the clinicodemographic factors associated with complications of continence procedures, the impact of concomitant surgery on the complication rate and the relationship between the incidence of cystitis and the method of postoperative bladder drainage. MATERIALS AND METHODS: We reviewed serious adverse events and adverse events in the Stress Incontinence Surgical Efficacy Trial, a randomized trial comparing Burch colposuspension to the autologous rectus fascial sling. Clinicodemographic variables were analyzed to determine those associated with adverse events using logistic regression analysis. Complications were stratified based on the presence or absence of concomitant surgery. Differences in complication rates (controlling for concomitant surgery) and cystitis rates (controlling for the bladder emptying method) were compared using Fisher's exact test. RESULTS: Blood loss (p = 0.0002) and operative time (p <0.0001) were significantly associated with an adverse event. Patients who underwent concomitant surgery had a significantly higher serious adverse event rate (14.2% vs 7.3%, p = 0.01) and adverse event rate (60.5% vs 48%, p <0.01) than patients who underwent continence surgery alone. Cystitis rates were higher in the sling vs the Burch group up to 6 weeks postoperatively regardless of concomitant surgery status (p <0.01). Intermittent self-catheterization increased the cystitis rate by 17% and 23% in the Burch and sling groups, respectively. CONCLUSIONS: Concomitant surgery at continence surgery increased the risk of complications. Sling surgery was associated with a higher risk of cystitis within the first 6 weeks postoperatively. Intermittent self-catheterization increased the risk of cystitis in each group. Complications were associated with surgical factors and not with patient related factors.