Uncovering the relationship between macrophages and polypropylene surgical mesh.

Currently, in vitro testing examines the cytotoxicity of biomaterials but fails to consider how materials respond to mechanical forces and the immune response to them; both are crucial for successful long-term implantation. A notable example of this failure is polypropylene mid-urethral mesh used in the treatment of stress urinary incontinence (SUI). The mesh was largely successful in abdominal hernia repair but produced significant complications when repurposed to treat SUI. Developing more physiologically relevant in vitro test models would allow more physiologically relevant data to be collected about how biomaterials will interact with the body. This study investigates the effects of mechanochemical distress (a combination of oxidation and mechanical distention) on polypropylene mesh surfaces and the effect this has on macrophage gene expression. Surface topology of the mesh was characterised using SEM and AFM; ATR-FTIR, EDX and Raman spectroscopy was applied to detect surface oxidation and structural molecular alterations. Uniaxial mechanical testing was performed to reveal any bulk mechanical changes. RT-qPCR of selected pro-fibrotic and pro-inflammatory genes was carried out on macrophages cultured on control and mechanochemically distressed PP mesh. Following exposure to mechanochemical distress the mesh surface was observed to crack and craze and helical defects were detected in the polymer backbone. Surface oxidation of the mesh was seen after macrophage attachment for 7 days. These changes in mesh surface triggered modified gene expression in macrophages. Pro-fibrotic and pro-inflammatory genes were upregulated after macrophages were cultured on mechanochemically distressed mesh, whereas the same genes were down-regulated in macrophages exposed to control mesh. This study highlights the relationship between macrophages and polypropylene surgical mesh, thus offering more insight into the fate of an implanted material than existing in vitro testing.

Predicting Prostate Surgery Outcomes from Standard Clinical Assessments of Lower Urinary Tract Symptoms To Derive Prognostic Symptom and Flowmetry Criteria.

BACKGROUND: Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes when interventional treatment is planned. OBJECTIVE: To develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort and derive thresholds for key clinical parameters. DESIGN, SETTING, AND PARTICIPANTS: From the UPSTREAM trial of 820 men seeking treatment for LUTS, analysis of bladder diary (BD), International Prostate Symptom Score (IPSS), IPSS-quality of life, and uroflowmetry data was performed for 176 participants who underwent prostate surgery and provided complete data. For external validation, data from a retrospective database of surgery outcomes in a Japanese urology department (n = 227) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Symptom improvement was defined as a reduction in total IPSS of ≥3 points. Multiple logistic regression, classification tree analysis, and random forest models were generated, including versions with and without BD data. RESULTS AND LIMITATIONS: Multiple logistic regression without BD data identified age (p = 0.029), total IPSS (p = 0.0016), and maximum flow rate (Qmax; p = 0.066) as predictors of outcomes, with area under the receiver operating characteristic curve (AUC) of 77.1%. Classification tree analysis without BD data gave thresholds of IPSS <16 and Qmax ≥13 ml/s (AUC 75.0%). The random forest model, which included all clinical parameters except BD data, had an AUC of 94.7%. Internal validation using the bootstrap method showed reasonable AUCs (69.6-85.8%). Analyses using BD data marginally improved the model fits. External validation gave comparable AUCs for logistic regression, classification tree analysis, and random forest models (all without BD; 70.9%, 67.3%, and 68.5%, respectively). Limitations include the significant number of men with incomplete baseline data and limited assessments in the external validation cohort. CONCLUSIONS: Outcomes of prostate surgery can be predicted preoperatively using age, total IPSS, and uroflowmetry data, with prognostic thresholds of 16 for IPSS and 13 ml/s for Qmax. PATIENT SUMMARY: This study identified key preoperative factors that can predict outcomes of prostate surgery for bothersome urinary symptoms, including which patients are at risk of a poor outcome.

The Effects of Age, Gender, and Postvoid Residual Volume on Catheterization Rates After Treatment with OnabotulinumtoxinA for Overactive Bladder.

Background: Transient increases in postvoid residual urine volume (PVR) requiring clean intermittent catheterization (CIC) have occurred with onabotulinumtoxinA treatment for overactive bladder (OAB). Objective: To evaluate onabotulinumtoxinA safety and the effect of age, gender, and maximum PVR (PVRmax) on CIC initiation in adults with OAB and urinary incontinence (UI). Design setting and participants: This was a pooled post hoc analysis of four placebo-controlled, multicenter randomized trials that included adults with idiopathic OAB after first onabotulinumtoxinA treatment (NCT00910845, NCT00910520, NCT01767519, NCT01945489). Patients had at least three urgency UI episodes over 3 d and at least eight micturitions per day, had inadequate management with at least one anticholinergic agent, and were willing to use CIC. Outcome measurements and statistical analysis: We measured the following outcomes: PVRmax within 12 wk after first treatment; CIC incidence; estimated functional capacity; PVR ratio (PVR/estimated functional capacity). Results and limitations: Of 1504 patients, 87.7% were women and 88.8% were White. The mean age was 60.5 yr across 10-yr age groups, baseline PVR was 13.8-35.0 ml, and estimated functional capacity was 293.5-475.7 ml. Mean baseline PVR was 21.3 ml overall versus 34.0 ml in the group that started CIC. The CIC incidence was 6.2% for women (range 1.1-8.4%) and 10.5% for men (range 0-14.6%). Higher CIC rates were observed for PVRmax >350 ml (women 91.9%, men 84.6%) in comparison to PVRmax of 201-350 ml (women 32.5%, men 17.4%) and PVRmax <200 ml (women 1.2%, men 1.6%). Overall, 2/1504 patients (both women) were unable to void spontaneously. The mean PVR ratio was highest at week 2. Some subgroups had small sample sizes. Conclusions: CIC incidence was low overall, was less frequent for women, was rare with PVRmax ≤200 ml, and did not appear to correlate with baseline PVR. Patient summary: After onabotulinumtoxinA treatment for OAB, patients sometimes insert a catheter to help in emptying their bladder after urinating. In this study, few patients needed a catheter, especially when less urine volume remained after urination.

Robotic ureteral reconstruction for benign ureteral strictures: a systematic review of surgical techniques, complications and outcomes : Robotic Ureteral Reconstruction for Ureteral Strictures.

INTRODUCTION: Robotic ureteral reconstruction (RUR) has been widely used to treat ureteral diseases. To summarize the surgical techniques, complications, and outcomes following RUR, as well as to compare data on RUR with open and laparoscopic ureteral reconstruction. METHODS: Our systematic review was registered on the PROSPERO (CRD42022309364) database. The PubMed, Cochrane and Embase databases were searched for publications in English on 06-Feb-2022. Randomised-controlled trials (RCTs) or non-randomised cohort studies with sample size ≥ 10 cases were included. RESULTS: A total of 23 studies were included involving 996 patients and 1004 ureters from 13 non-comparative, and 10 retrospective comparative studies. No RCT study of RUR was reported. The success rate was reported ≥ 90% in 15 studies. Four studies reported 85-90% success rate. Meta-analyses for comparative studies showed that RUR had significantly lower estimated blood loss (EBL) (P = 0.006) and shorter length of stay (LOS) (P < 0.001) than the open approach. RUR had shorter operative time than laparoscopic surgery (P < 0.001). CONCLUSIONS: RUR is associated with lower EBL and shorter LOS than the open approach, and shorter operative time than the laparoscopic approach for the treatment of benign ureteral strictures. However, further studies and more evidence are needed to determine whether RUR is more superior.

Estradiol-17ß [E2] stimulates wound healing in a 3D in vitro tissue-engineered vaginal wound model.

Childbirth contributes to common pelvic floor problems requiring reconstructive surgery in postmenopausal women. Our aim was to develop a tissue-engineered vaginal wound model to investigate wound healing and the contribution of estradiol to pelvic tissue repair. Partial thickness scalpel wounds were made in tissue models based on decellularized sheep vaginal matrices cultured with primary sheep vaginal epithelial cells and fibroblasts. Models were cultured at an airliquid interface (ALI) for 3 weeks with and without estradiol-17ß [E2]. Results showed that E2 significantly increased wound healing and epithelial maturation. Also, E2 led to collagen reorganization after only 14 days with collagen fibers more regularly aligned and compactly arranged Additionally, E2 significantly downregulated α-SMA expression which is involved in fibrotic tissue formation. This model allows one to investigate multiple steps in vaginal wound healing and could be a useful tool in developing therapies for improved tissue healing after reconstructive pelvic floor surgery.

A diagnostic conundrum: Is it a periurethral diverticulum/cyst or a bulking agent (Bulkamid)?

INTRODUCTION: Urethral bulking agents are commonly used to manage female stress urinary incontinence (SUI) as they have been suggested to be safe, efficacious, and a minimally invasive surgical option. Bulkamid is a newer bulking agent that has been introduced and promoted in the market for use. It is non-particulate in nature with high tissue biocompatibility, and consequently, it is difficult to differentiate between Bulkamid and a periurethral cyst on magnetic resonance imaging (MRI). This, therefore, presents a diagnostic dilemma. METHODS AND MATERIALS: Here we describe two cases with previous injections of Bulkamid referred to our Centre for management of a presumed periurethral diverticulum based on MRI findings. Both patients were reviewed and examined in outpatient clinics with MRI findings discussed at MDT, further imaging was required. RESULTS: We found that a limited noncontrast computed tomography (CT) pelvis, followed by a voiding cystometrogram (VCMG), and then a repeat limited noncontrast CT pelvis effectively differentiated between Bulkamid and these presumed periurethral diverticulae. The theory behind this was that during micturition, the contrast would pass through to the urethral diverticulum and appear as high-density (bright) material within the periurethral region (the pre-VCMG was required to prove that any high-density material was due to the contrast and not pre-existing high-contrast material). CONCLUSION: A CT scan done in conjunction with a VCMG is likely to be more effective in differentiating between Bulkamid and a true periurethral diverticulum than an MRI scan. Appropriate diagnostic evaluation of periurethral lesions can lead to time-saving and cost-effective patient management as this will bypass the need for unnecessary investigations and possible unwarranted surgical intervention.

A physiologically relevant, estradiol-17ß [E2]-responsive in vitro tissue-engineered model of the vaginal epithelium for vaginal tissue research.

AIMS: There are many situations where preclinical models of the human vagina would be valuable for in vitro studies into the pathophysiology of vaginally transmitted diseases, microbicide efficacy, irritability testing, and particularly, for assessing materials to be inserted in the vagina for support of the pelvic floor. The aim of this study is to develop a physiologically relevant, low cost, and ethically suitable model of the vagina using sheep vaginal tissue (SVT) to reduce the need for animal testing in gynecological research. METHODS: Tissue-engineered (TE) vaginal models were developed by culturing primary vaginal epithelial cells and vaginal fibroblasts, isolated from the native SVTs on decellularized sheep vaginal matrices at an air-liquid interface. Morphological analyses of the models were conducted by performing hematoxylin and eosin staining and further characterization was done by immunohistofluorescence (IHF) of structural proteins and cytokeratins. RESULTS: Histological analysis of the models revealed a gradual formation of a stratified epithelium on our decellularized matrices and cell metabolic activity remained high for 21 days as measured by the resazurin assay. Our models showed a dose-dependent response to estradiol-17ß [E2 ] with an increase in the vaginal epithelium thickness and cellular proliferation under higher E2 concentrations (100-400 pg/ml). The physiological relevance of these results was confirmed by the IHF analysis of Ki67, and cytokeratins 10 and 19 expression. CONCLUSION: In this study, we have developed an estradiol-responsive TE vaginal model that closely mimics the structural and physiological properties of the native SVT.

Management strategies and outcome of ureterovaginal fistulae: A systematic review and meta-analysis.

BACKGROUND: Genitourinary fistula is a distressful condition involving mental, social, marital, and financial repercussions. OBJECTIVE: The objective of this study is to systematically evaluate etiology, clinical presentation, diagnosis, the timing of repair, and perform a meta-analysis evaluating the success rate of various treatment modalities with respect to time taken to seek treatment. SEARCH STRATEGY: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in April 2020 according to the PRISMA statement. Seventeen studies were included in the final analysis and all were retrospective in design. SELECTION CRITERIA: Each article was rated by the evidence-based medicine levels of evidence scale and the Methodological Index for Nonrandomized Studies scale for assessment of bias among nonrandomized studies. MAIN RESULTS: Of the 799 fistulae reported in 17 studies, endoscopic management was done in 35.6% (12 studies), whereas surgical management was preferred in 85.6% fistulae (15 studies). The pooled success of endoscopic stenting was 32% (95% confidence interval [CI]: 7-64) and 100% (95% CI: 98-100) in operated patients. Patients who underwent stenting within 2 weeks (20%), 2-6 weeks (21%), and >6 weeks (40%) had pooled success rates of 95% (95% CI: 87-100), 46% (95% CI: 0-100), and 20% (95% CI: 1-49), respectively. Patients who underwent surgical management <6 weeks (15.9%) and >6 weeks (22%) of diagnosis had pooled success rates of 100% (95% CI: 99-100) and 100% (95% CI: 99-100), respectively. CONCLUSIONS: Stent placement as early as <6 weeks (preferably < 2 weeks) had better outcomes as compared to >6 weeks. Proceeding to surgery regardless of timing in cases of stent failure seems to be a feasible option.

Prostate Surgery for Men with Lower Urinary Tract Symptoms: Do We Need Urodynamics to Find the Right Candidates? Exploratory Findings from the UPSTREAM Trial.

BACKGROUND: Identifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging. OBJECTIVE: To identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial. DESIGN, SETTING, AND PARTICIPANTS: A randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274). INTERVENTION: Men were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Men underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures. RESULTS AND LIMITATIONS: The recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age <74 yr, Qmax <9.8 ml/s, bladder outlet obstruction index >47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup. CONCLUSIONS: Treatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups. PATIENT SUMMARY: Baseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone.

Contemporary Outcomes of Surgery for Primary and Recurrent Genitourinary Fistulae in a Well-resourced Country.

BACKGROUND: Urinary fistula (UF) is a global health problem but less common in well-resourced countries. Over the past decade there has been a trend toward managing UF in dedicated centres. Most of the evidence for surgical treatment is from individual case series, with few publications that involve high numbers. We describe the repair of recurrent and complex UF cases and outcomes in a tertiary referral setting. OBJECTIVE: To describe UF aetiology, repair techniques, and outcomes. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study of a series of patients undergoing UF repair at a specialist unit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We describe the aetiology, cure rate, complications, and postoperative urinary incontinence rates for the series of UF cases. RESULTS AND LIMITATIONS: A consecutive series of 98 patients was identified, all of whom were tertiary referrals. Of these, 31 (31.6%) had at least one prior attempt at repair at another centre. The median age was 48 yr (interquartile range [IQR] 40-60.25). The median time from occurrence to repair was 12 mo (IQR 6-12). UF occurred most commonly following hysterectomy (48.0%), Caesarean section (9.2%), other gynaecological surgery (7.1%), and anti-incontinence surgery (7.1%). Complex fistulae (eg, repeat cases, radiation, ureteric involvement) comprised 41 of the cases (41.8%). Most patients with vesicovaginal fistula underwent repair via a transabdominal approach (70.4%). Tissue interposition was used in 96 cases (98%). There were no Clavien-Dindo grade >3 complications. Two patients (2%) had a persistent UF postoperatively. Two patients (2%) developed recurrence more than 2 yr after their initial repair, and both were successfully repaired at our centre. Twelve patients (12.3%) developed de novo overactive bladder, 22 (22.5%) developed stress urinary incontinence (13 had subsequent incontinence surgery), and two (2%) developed bladder pain (both had a subsequent cystectomy). CONCLUSIONS: Despite a high rate of recurrent and complex UF, successful lasting closure was achieved in 96% of our cases. A minority of patients developed other problems such as de novo overactive bladder and stress urinary incontinence that may require further treatment. PATIENT SUMMARY: Urinary fistula is an abnormal opening or connection in the urinary tract and is less common in well-resourced countries. As a consequence, management of this condition is more frequently undertaken at specialist units. Even patients with a complex fistula and those who have had multiple attempts at repair can experience a cure. Urinary leakage is a common complication after the operation but can be successfully managed with surgery.

Prostate-specific Antigen Testing as Part of a Risk-Adapted Early Detection Strategy for Prostate Cancer: European Association of Urology Position and Recommendations for 2021.

BACKGROUND: Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer-specific mortality rates. OBJECTIVE: To present the position of the European Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer. EVIDENCE ACQUISITION: The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU's position in 2021. EVIDENCE SYNTHESIS: The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer-specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council's screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans. CONCLUSIONS: This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives. PATIENT SUMMARY: The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test.

Tissue engineering: recent advances and review of clinical outcome for urethral strictures.

PURPOSE OF REVIEW: Urethrotomy remains the first-line therapy in the treatment of a urethral stricture despite data showing no real chance of a cure after repeated urethrotomies. An anastomotic or an augmentation urethroplasty using oral mucosa can be offered to patients following failed urethrotomy. The potential for a tissue engineered solution as an alternative to native tissue has been explored in recent years and is reviewed in this article. RECENT FINDINGS: More than 80 preclinical studies have investigated a tissue-engineered approach for urethral reconstruction mostly using decellularized natural scaffolds derived from natural extracellular matrix with or without cell seeding. The animal models used in preclinical testing are not representative of disease processes seen with strictures in man. The available clinical studies are based on small noncontrolled series. SUMMARY: There is a potential role for tissue engineering to provide a material for substitution urethroplasty and work has demonstrated this. Further work will require a rigorous basic science programme and adequate evaluation of the material prior to its introduction into clinical practice. The research with tissue engineering applied to the urethra has not yet been resulted in a widely available material for clinical use that approaches the efficacy seen with the use of autologous grafts.

A Systematic Review and Meta-analysis of Adjuncts to Minimally Invasive Treatment of Urethral Stricture in Men.

CONTEXT: Urethral stricture disease (USD) is initially managed with minimally invasive techniques such as urethrotomy and urethral dilatation. Minimally invasive techniques are associated with a high recurrence rate, especially in recurrent USD. Adjunctive measures, such as local drug injection, have been used in an attempt to reduce recurrence rates. OBJECTIVE: To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD. EVIDENCE ACQUISITION: A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist. EVIDENCE SYNTHESIS: A total of 26 studies were included in the systematic review, from which 13 different adjuncts were identified, including intralesional injection (triamcinolone, n = 135; prednisolone, n = 58; mitomycin C, n = 142; steroid-mitomycin C-hyaluronidase, n = 103, triamcinolone-mitomycin C-N-acetyl cysteine, n = 50; platelet-rich plasma, n = 44), intraluminal instillation (mitomycin C, n = 20; hyaluronic acid and carboxymethylcellulose, n = 70; captopril, n = 37; 192-iridium brachytherapy, n = 10), application via a lubricated catheter (triamcinolone, n = 124), application via a coated balloon (paclitaxel, n = 106), and enteral application (tamoxifen, n = 30; deflazacort, n = 36). Overall, 13 randomised controlled trials were included in the meta-analysis. Use of any adjunct was associated with a lower rate of USD recurrence (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.27-0.50; p <  0.001) compared to no adjunct use. Of all the adjuncts, mitomycin C was associated with the lowest rate of USD recurrence (intralesional injection: OR 0.23, 95% CI 0.11-0.48; p <  0.001; intraluminal injection: OR 0.11, 95% CI 0.02-0.61; p =  0.01). Urinary tract infection (2.9-14%), bleeding (8.8%), and extravasation (5.8%) were associated with steroid injection; pruritis of the urethra (61%) occurred after instillation of captopril; mild gynaecomastia (6.7%) and gastrointestinal side effects (6.7%) were associated with oral tamoxifen. CONCLUSIONS: Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence. PATIENT SUMMARY: We reviewed studies on additional therapies (called adjuncts) to minimally invasive treatments for narrowing of the urethra in men. Adjuncts such as mitomycin C injection result in a lower recurrence rate compared to no adjunct use. The use of adjuncts appeared to be safe and complications are uncommon; however, the studies were small and of low quality.

The Modified Prone Jack-knife Position for the Excision of Female Urethral Diverticula.

BACKGROUND: Female urethral diverticula (UD) are an uncommon and often overlooked aetiology in women presenting with lower urinary tract symptoms, urethral pain, and recurrent urinary tract infection. With increasing awareness, appropriate imaging is more commonly undertaken with consideration given to surgical management. OBJECTIVE: The video presented demonstrates the technique for excising large and/or complex UD using a modified prone jack-knife position-a position that offers excellent surgical access and allows the surgeon to operate in a more ergonomic position. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of the data on patients undergoing excision of UD at a tertiary referral unit was performed. SURGICAL PROCEDURE: Urethral and suprapubic catheters (±insertion of ureteric stents) were placed in supine position. UD excised in the modified prone jack-knife position (±placement of a Martius flap). MEASUREMENTS: Subjective cure rate, recurrence rate, rates of postoperative urinary incontinence, need for secondary incontinence procedure, and postoperative complications were measured. RESULTS AND LIMITATIONS: A total of 121 patients were operated on in the study period. The mean follow-up time was 10 mo (range 3-40). The most frequent presenting symptoms included a vaginal mass (n = 76, 63%), followed by dysuria (n = 72, 60%) and pelvic pain (n = 71, 59%). An identifiable aetiological factor was present in 45 patients, including traumatic vaginal delivery (18, 15%), prior periurethral surgery (17, 14%), and urethral dilatation (10, 8%). All patients underwent postvoiding magnetic resonance imaging (MRI) to confirm the diagnosis and plan surgery. UD ranged in maximum diameter from 8 to 48 mm, with a mean of 43 mm (standard deviation 9.24). The most common anatomical location was midurethral (55, 46%), followed by distal (36, 30%), proximal (25, 21%), and full length (5, 4%). Most UDs were single in configuration (74%), followed by multiloculated (15%), saddle shaped (7%), and circumferential (5%). On preoperative videourodynamics, 17 (14%) had stress urinary incontinence. UD excision was undertaken in the modified prone jack-knife position in all cases. A Martius flap was utilised in 36 (30%). The median postoperative postvoiding residual was 26 ml (interquartile range 0-40). In total, 88 (73%) patients were continent postoperatively and 16 (13%) experienced de novo stress urinary incontinence. Of the 37 with pre-existing stress incontinence symptoms, 20 (54%) were continent after operation. A total of 14 patients had subsequent autologous fascial sling at 6 mo. In total, five symptomatic recurrences occurred (4%); of these patients, three elected to undergo surgical excision, all of whom had symptom resolution and were continent after operation. A total of 11 patients (9%) experienced a Clavien-Dindo grade I-II complication within 90 d after operation. Five patients complained of dyspareunia, which resolved by 6 mo. CONCLUSIONS: The modified prone jack-knife position facilitates excellent access for excision of both simple and complex UDs. This positioning of the patient is not widely recognised amongst urologists. Using this approach, there were low rates of symptomatic recurrence and de novo stress incontinence at medium-term follow-up. Associated urinary incontinence resolves in over half of patients following UD excision; hence, we advocate deferring any incontinence procedure until after the results of surgery are established. PATIENT SUMMARY: Surgical removal of urethral outpouching (diverticula) in women is challenging due to its potential to damage the nearby sphincter muscle, which controls continence, or the urethra tube. Placement of patients on their front, rather than on their back, provides excellent access for the surgical removal of urethral diverticula. With this approach, we achieved excellent rates of cure and low rates of urinary incontinence at an average follow-up of 10 mo.

Which Drug to Discontinue 3 Months After Combination Therapy of Tadalafil plus Tamsulosin for Men with Lower Urinary Tract Symptom and Erectile Dysfunction? Results of a Prospective Observational Trial.

BACKGROUND: Safety and efficacy of tamsulosin and tadalafil for men with benign prostatic enlargement (BPE) and/or erectile dysfunction (ED) are defined. However, there are only a few pilot studies on combination therapy with these drugs for men with lower urinary tract symptom (LUTS)/BPE and ED. Moreover, preliminary reports are limited to 12 wk, without any information about subsequent therapies. OBJECTIVE: To evaluate the impact of discontinuation of tamsulosin versus tadalafil 12 wk after combination therapy. DESIGN, SETTING, AND PARTICIPANTS: Fifty consecutive patients with moderate-to-severe LUTS (International Prostate Symptom Score [IPSS] > 7) and mild-to-severe ED (International Index of Erectile Function-5 [IIEF-5] < 22) were treated with combination therapy (tamsulosin 0.4mg/d plus tadalafil 5mg/d) for 12 wk. After 12 wk, 25 patients discontinued tamsulosin (Group TAD), while 25 patients discontinued tadalafil (Group TAM). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy variables were IPSS (total, voiding, storage) and IIEF-5. Paired samples t test and analysis of variance were used. RESULTS AND LIMITATIONS: Groups TAD and TAM presented similar features (age, BMI, metabolic profile) including symptoms scores at baseline. Similar and significant improvements in IPSS (total, voiding, and storage) and IIEF-5 were recorded in both groups after 12 wk of combination therapy (all p< 0.001). Total IPSS was similar between the two groups at the end of the trial. However, we found between-group significant differences from baseline to 24 wk and from 12 to 24 wk in storage-IPSS (Group TAD: -3.32 vs Group TAM: -1.24, p= 0.002; Group TAD: +0.24 vs Group TAM: +1.20, p= 0.040, respectively) and in IIEF-5 (Group TAD: +4.64 vs Group TAM: +0.16, p< 0.001; Group TAD: -1.64 vs Group TAM: -4.40, p= 0.003). No significant treatment-related adverse event was recorded in both groups. CONCLUSIONS: After 12 wk of combination therapy, monotherapy with tadalafil for further 12 wk allows to preserve the improvement of storage IPSS and IIEF-5, in addition to total IPSS. PATIENT SUMMARY: In this report we evaluated the discontinuation of tamsulosin or tadalafil after 12 wk of combination therapy. We found that tadalafil monotherapy, for a further 12 wk, aids in retaining the improvement of storage symptoms and erectile function.

A Systematic Review of Surgical interventions for the Treatment of Bladder Pain Syndrome/Interstitial Cystitis.

CONTEXT: Bladder pain syndrome/interstitial cystitis (BPS/IC) is a poorly understood chronic debilitating condition. Surgery is reserved for severe refractory cases; however, there is no consensus on patient selection or optimal approach. OBJECTIVE: To evaluate the evidence relating to the safety and efficacy of surgical interventions for treating BPS/IC. EVIDENCE ACQUISITION: PubMed and Scopus databases were searched for original studies, using keywords "cystectomy", "interstitial cystitis", and "bladder pain syndrome". Articles were reviewed and screened by three independent reviewers. EVIDENCE SYNTHESIS: A total of 450 patients were identified from 20 eligible studies: mean age was 54.5 yr and 90.2% were female. The median duration of symptoms preoperatively was 60 mo (range 9-84), with a mean follow-up of 45.5 mo. A total of 448 patients underwent surgery: subtotal cystectomy with cystoplasty (48.6%), cystectomy and orthotopic neobladder (21.9%), cystectomy and ileal conduit (11.2%), and urinary diversion only (18.3%). Symptomatic improvement occurred in 77.2%, with higher rates in the total cystectomy and orthotopic neobladder group. Thirty-one patients (6.9%) required secondary total cystectomy and/or ileal conduit diversion; 48.4% subsequently improved. Seventeen studies reported 102 complications overall (26.5%). Overall mortality was 1.3%. CONCLUSIONS: Overall surgical intervention is associated with a 23% risk of failure to improve symptoms. Higher rates of improvement were reported in patients with total cystectomy. Interpretation should be guarded given the small patient number, multiple centres, and variable outcome measurements. There is a need for prospective randomised studies to answer questions regarding patient selection and optimal surgical approach. PATIENT SUMMARY: In this review, we looked at the outcomes of surgery for treatment-refractory bladder pain syndrome/interstitial cystitis. We found overall symptom improvement in 77.2% of patients with a complication rate of 26.5%. However, there remains a need for further studies of higher quality to identify patients who will have symptom improvement and the best surgical option.

Treatment decision-making among men with lower urinary tract symptoms: A qualitative study of men's experiences with recommendations for patient-centred practice.

AIMS: To inform and guide patient-centred care for men with lower urinary tract symptoms (LUTS), by providing in-depth qualitative evidence regarding men's perspectives on treatment decision-making for LUTS. METHODS: An interview study of men recruited from 26 English urology departments. Purposive sampling captured surgical/nonsurgical treatment decisions, and diversity in demographics and symptom burden, in men who had urodynamics and those who did not. After diagnostic assessments, men were interviewed either pre-treatment or after LUTS surgery. Thematic analysis was conducted. Participants' descriptions of how LUTS treatment decisions were made were categorised as patient-led, doctor-led, or shared. RESULTS: A total of 41 men participated (25 pre-treatment, 16 post-surgery), ages 52-89. Twenty out of 41 described the treatment decision as shared with their consultant, 14 as doctor-led, and seven as patient-led. There was no obvious association between treatment decision-making style and patients' satisfaction with either clinicians' role in their decision or their treatment decision. Incomplete or rushed discussions and misperceptions of LUTS and its treatment were reported, indicating a risk of suboptimal decision-making support by clinicians. As well as clinician opinion, men's treatment decision-making was influenced by the results of urological assessments, comparing current symptoms with possible side-effects of surgery, and others' experiences and opinions. CONCLUSIONS: Men with LUTS report and prefer different kinds of decision-making support from their clinicians, who must tailor their input to patients' preferences and needs. Patients' treatment decision-making involves multiple factors and can be challenging, and areas of inadequate clinician support were identified. Recommendations for patient-centred consultations about LUTS treatment are presented.

Outcomes of combination therapy with daily tadalafil 5 mg plus tamsulosin 0.4 mg to treat lower urinary tract symptoms and erectile dysfunction in men with or without metabolic syndrome.

BACKGROUND: The aim of this study was to assess the impact of tadalafil 5 mg/die plus tamsulosin 0.4 mg/die combination therapy on lower urinary tract symptoms (LUTS) and erectile dysfunction (ED), according to presence vs. absence of metabolic syndrome (MetS). METHODS: Seventy-five consecutive men presenting with ED and LUTS were enrolled. Patients were divided into two groups according to MetS presence. All subjects were treated with combination therapy for 12 weeks. Patients were re-evaluated after treatment with uroflowmetry and post-void residual volume (PVR), International Prostate Symptoms Score (IPSS), IPSS Quality of Life (QoL), overactive bladder questionnaire (OAB-q) and International Index Erectile Function-5 (IIEF-5) Score. RESULTS: After enrollment, 50 patients were included: 31 (62.0%) with MetS and 19 (38.0%) without MetS. At baseline, patients without MetS showed a significantly better IPSS, IIEF and OAB-q, as compared to those with MetS. After 12 weeks of combination therapy LUTS, ED and flowmetry significantly improved in both groups (P<0.001). The improvement after 12 weeks was similar between groups in all parameters (P>0.05), except for ∆OAB-q that was significantly better for patients with MetS (P=0.028). Nevertheless, total IPSS, all IPSS subscores and OAB-q were significantly better at 12 weeks in men without MetS (P<0.05). Despite IIEF-5 was significantly different at baseline, after 12 weeks of combination therapy, erectile function was similar in men with or without METS: 16.3±3.8 vs. 17.7±4.7 (P=0.238). No serious adverse event (AE) was reported, and complications were comparable between groups (P>0.05). CONCLUSIONS: Patients with MetS have worse LUTS and ED profiles. However, tadalafil plus tamsulosin combination treatment provided them a similar ED profile and a greater relief of overactive bladder (OAB) symptoms at the end of the trial. Combination therapy had the same safety profile in men besides MetS. Further randomized controlled trials are needed.

Urodynamics tests for the diagnosis and management of bladder outlet obstruction in men: the UPSTREAM non-inferiority RCT.

BACKGROUND: Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. OBJECTIVES: The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. DESIGN: This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. SETTING: Urology departments of 26 NHS hospitals in England. PARTICIPANTS: Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. INTERVENTIONS: Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). MAIN OUTCOME MEASURES: The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. RESULTS: A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (-0.33, 95% CI -1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43-44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. LIMITATIONS: The trial met its predefined recruitment target, but surgery rates were lower than anticipated. CONCLUSIONS: Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. FUTURE WORK: Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56164274. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

After hospital referral, men with bothersome lower urinary tract symptoms (LUTS) are assessed with standard tests. These include measurement of urine flow rate, bladder diaries and questionnaires, including the International Prostate Symptom Score (IPSS). UPSTREAM (Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods) researched whether or not including an extra test, urodynamics (UDS), helps when considering treatment options. UDS is a more invasive test and measures pressure in the bladder to check whether or not the prostate is causing obstruction. It was presumed that, if there is no obstruction, surgery would not be offered, so that using UDS would reduce the number of prostate operations. Each man participating (820 in total) was assessed with the standard tests. Around half of them had no extra tests (the 'routine care' arm of the trial); the rest had the UDS tests (the 'UDS' arm). Men then went on to have treatment, which they chose having discussed their test results with a urologist. IPSS and other symptom scores were examined for each man 18 months after joining the trial. At 18 months, surgery outcomes were known for 792 men and IPSS was known for 669 men. We investigated if the two trial arms showed similar changes in the IPSS and if there were fewer operations done in the UDS arm. We identified similar reductions in the IPSS in both arms. However, UDS tests did not reduce the number of operations. Analysing all the costs, it was found that a pathway including UDS costs more than routine care. Interviews were conducted that showed that men found UDS acceptable, and that the additional information helped both the men and their doctors consider which treatment would be most appropriate. These results do not support the routine use of UDS in the assessment of every man considering prostate surgery for LUTS. Further exploration of the data may identify circumstances in which UDS could be helpful.