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Context Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice. Objective To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of urethral strictures in females and transgender patients. Evidence acquisition The panel performed a literature review on these topics covering a time frame between 2008 and 2018 and used predefined inclusion and exclusion criteria for study selection. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on the review of the available literature and after panel discussion. Evidence synthesis Management of urethral strictures in females and transgender patients has been described in a few case series in the literature. Endoluminal treatments can be used for short, nonobliterative strictures in the first line. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. Conclusions Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations. Patient summary Although different techniques are available to manage narrowing of the urethra (called a stricture), not every technique is appropriate for every type of stricture. These guidelines, developed on the basis of an extensive literature review, aim to guide physicians in selecting the appropriate technique(s) to treat a specific type of urethral stricture in females and transgender patients. Take Home Message Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. Management of urethral strictures in females and transgender patients is complex and a multitude of techniques are available. Selection of the appropriate technique is crucial and these guidelines provide relevant recommendations.

Subfertility is a risk factor for testicular cancers (TT), and conversely, TT may induce subfertility due to local and regional toxic effects. We aimed to identify the association between TT characteristics and pre-orchidectomy azoospermia. A systematic review of the literature was performed according to the PRISMA checklist. Overall, eight non-randomised studies involving 469 men with TT (azoospermia, n = 57; no azoospermia n = 412) were included in the qualitative analysis. Bilateral TT (12.3% vs 2.9% in non-azoospermia), non-seminoma germ cell tumours (6.4% vs 1.9%), germ cell neoplasia in-situ (GCNIS) (11.1% vs 1.2%), stage 2-3 disease (22.2% vs 0%), Sertoli Cell only (SCO) on biopsy (60% vs 37.5%) and a history of undescended testis (UDT) (66.7% vs 50%) were more common in azoospermic men. FSH levels are higher (18.7-23.2 mIU/L vs

The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65–100% (mean/median follow-up, 12–59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit–harm balance and surgeon’s skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

Objective To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of male urethral stricture disease. Evidence acquisition The panel performed a literature review on these topics covering a time frame between 2008 and 2018, and used predefined inclusion and exclusion criteria for the literature to be selected. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on a review of the available literature and after panel discussion. Evidence synthesis Management of male urethral strictures has extensively been described in literature. Nevertheless, few well-designed studies providing high level of evidence are available. In well-resourced countries, iatrogenic injury to the urethra is one of the most common causes of strictures. Asymptomatic strictures do not always need active treatment. Endoluminal treatments can be used for short, nonobliterative strictures at the bulbar and posterior urethra as first-line treatment. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques, and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. Conclusions Management of male urethral strictures is complex, and a multitude of techniques are available. Selection of the appropriate technique is crucial, and these guidelines provide relevant recommendations. Patient summary Injury to the urethra by medical interventions is one of the most common reasons of male urethral stricture disease in well-resourced countries. Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. These guidelines, developed based on an extensive literature review, aim to guide physicians in the selection of the appropriate technique(s) to treat a specific type of urethral stricture.

Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice.To present a summary of the 2021 European Association of Urology (EAU) guidelines on diagnosis, classification, perioperative management, and follow-up of male urethral stricture disease.The panel performed a literature review on the topics covering a time frame between 2008 and 2018, and using predefined inclusion and exclusion criteria for the literature. Key papers beyond this time period could be included if panel consensus was reached. A strength rating for each recommendation was added based on a review of the available literature after panel discussion.Routine diagnostic evaluation encompasses history, patient-reported outcome measures, examination, uroflowmetry, postvoid residual measurement, endoscopy, and urethrography. Ancillary techniques that provide a three-dimensional assessment and may demonstrate associated abnormalities include sonourethrography and magnetic resonance urethrogram, although these are not utilised routinely. The classification of strictures should include stricture location and calibre. Urethral rest after urethral manipulations is advised prior to offering urethroplasty. An assessment for urinary extravasation after urethroplasty is beneficial before catheter removal. The optimal time of catheterisation after urethrotomy is72 h, but is unclear following urethroplasty and depends on various factors. Patients undergoing urethroplasty should be followed up for at least 1 yr. Objective and subjective outcomes should be assessed after urethral surgeries, including patient satisfaction and sexual function.Accurate diagnosis and categorisation is important in determining management. Adequate perioperative care and follow-up is essential for achieving successful outcomes. The EAU guidelines provide relevant evidence-based recommendations to optimise patient work-up and follow-up.Urethral strictures have to be assessed adequately before planning treatment. Before surgery, urethral rest and infection prevention are advised. After urethral surgery, x-ray dye tests are advised before removing catheters to ensure that healing has occurred. Routine follow-up is required, including patient-reported outcomes. These guidelines aim to guide doctors in the diagnosis, care, and follow-up of patients with urethral stricture.

Context Four techniques for graft placement in one-stage bulbar urethroplasty have been reported: dorsal onlay (DO), ventral onlay (VO), dorsolateral onlay (DLO), and dorsal inlay (DI). There is currently no systematic review in the literature comparing these techniques. Objective To assess if stricture recurrence and secondary outcomes vary between the four techniques and to assess if one technique is superior to any other. Evidence acquisition The EMBASE, MEDLINE, and Cochrane Systematic Reviews—Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED) databases and ClinicalTrials.gov were searched for publications in English from 1996 onwards. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), observational studies (cohort, case-control/comparative, single-arm), and case series with ≥20 adult male participants were included. Evidence synthesis A total of 41 studies were included involving 3683 patients from one RCT, four NRCSs, and 36 case series. Owing to the overall low quality of the evidence, a narrative synthesis was performed. Conclusions No single technique appears to be superior to another for bulbar free graft urethroplasty. Both DO and VO are suitable for bulbar augmentation urethroplasty, with a ≤20% recurrence rate over medium-term follow-up. No recommendations can be made regarding DI or DLO techniques owing to the paucity of evidence. Secondary outcomes including sexual function, and complications are infrequently reported. Recurrence rates deteriorate in the long term for both DO and VO procedures. Patient summary We reviewed the evidence for four different skin-graft techniques used to repair narrowing of a section of the urethra (bulbar urethra, under the scrotum and perineum) in men. Two of the techniques seem to give consistent results, with recurrence rates lower than 20%. Recurrence rates increase over time, so patients should continue to monitor their symptoms. There is poorer reporting of other outcomes such as sexual function, urinary symptoms, and complications, and it is possible that these occur more frequently than the current data suggest.

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.

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.

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.To systematically review evidence for the efficacy and safety of adjuncts used alongside minimally invasive treatment of USD.A systematic review of the literature published between 1990 and 2020 was conducted in accordance with the PRISMA checklist.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.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.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.

Urethrotomy remains the first-line therapy in the treatment of a urethral stricture despite data showing no real chance of a cure after repeated urethroplasties. An anastomotic or an augmentation urethroplasty with oral mucosa should be offered to patients with a failed urethrotomy. The availability of grafts can be a concern for both patients and surgeons. The potential for a tissue-engineered solution has been explored in recent years and is explored in this article.More than 80 preclinical studies have investigated a tissue-engineered approach for urethral reconstruction mostly using decellularized natural scaffolds 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 were of small sample size and lacked control groups. The choice of biomaterial were mostly acellular matrices derived from natural extracellular matrix. The reported success rates in the pilot clinical studies were highly variable.The research with tissue engineering of the urethra has not yet been translated into a clinically available material. This is an area where much more research is needed and we would conclude that it is an area of unmet clinical need where users of tissue-engineered urethra in the future need to carry out a rigorous basic science programme and need to be cautious in drawing conclusions based on initial experience and report on long-term clinical results.

Context In recent years, there has been a rapid uptake in the use of laparoscopic and robotic surgery within urological oncological surgery. There is now growing interest in applying these surgical techniques to functional and reconstructive urology (FRU). Objective To provide an overview of the use of robotic surgery within the sphere of functional and reconstructive urology and discuss the research needs and the likely role of robotic technology in future. Evidence acquisition A PubMed-based literature review performed in March 2019 identified all articles published regarding the use of robotic surgery within FRU for the reconstruction of the upper tracts, bladder, bladder neck, pelvic floor, and urinary sphincter; creation of urinary diversion; and repair of genitourinary fistulae. Evidence synthesis There is a need to study the robotic approach in carefully designed prospective studies to better establish safety and clinical efficacy as well as the economic viability as compared with laparoscopic and open approaches. Conclusions The use of the robotic minimally invasive approach has many potential advantages; however, there is a need for a high level of technical expertise and experience, especially in some of the complex and technically challenging scenarios often seen within FRU. Surgeons should ensure that they have received sufficient training in not only the surgical principles of FRU, but also the assessment, management, and follow-up of patients. Moreover, it is imperative not to compromise important surgical steps. Patient summary In this report, we looked into the use of robotic technologies in the treatment of functional and reconstructive problems of the urinary tract. We found that the robotic approach has not yet been evaluated in prospective clinical studies in this field. There is a need for carefully designed prospective studies to establish the safety and efficacy of robotic surgeries.

Objectives: To look at the changing role of cystoplasty in the neuropathic population. Design: Retrospective case series. Setting: Single center over a 10-year period from 2004 to 2014. Participants and intervention: In 1995, the Princess Royal spinal injuries unit published the outcomes of 78 neuropathic patients who had undergone cystoplasty in the 10-year period from 1982 to 1992. [Singh G, Thomas DG. Enterocystoplasty in the neuropathic bladder. Neurourol Urodyn 1995; 14(1): 5–10.]. In this series, we review 51 consecutive patients undergoing the same operation over a 10-year period from 2004 to 2014 in the same single unit. Outcome measures: Demographic data were collected to include patient age, condition, and previous treatments. Pre- and post-operative details included sphincter insertions, renal function, continence rates, and complications. Results: Despite an increase in the number of patients seen at the unit, there were considerably fewer cystoplasty procedures performed in the current series (51 vs. 78 in the 1982–1992 series). There were also significantly fewer patients with spina bifida and fewer concomitant sphincter insertions in the latter series (eight patients vs. 52 in the 82/92 series). Nevertheless, similar outcomes are observed between the current and 1982–1992 series, with continence rates of 93.7 and 93.6%, respectively and low numbers of reported adverse events for both retrospective cohorts. Conclusions: Cystoplasty remains a safe and effective option for the management of neuropathic bladder in a carefully selected group of patients.

Introduction In the last decade therapeutic options for patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) have constantly increased. Although transurethral resection of the prostate (TURP) is still considered the surgical gold standard, different lasers and advanced techniques have been introduced as alternatives to TURP. Evidence acquisition A non-systematic Medline/Pubmed literature search was performed with different combination of terms including: "BPH," "M-TURP," "B-TURP" "bladder outlet obstruction," "YAG laser," "Diode laser," "Potassium titanyl phosphate," "KTP," "bladder outlet obstruction" (BOO), "BOO in small prostate". Only studies reporting prostate volume ≤40 cc were considered for this review. Evidence syntesis Current evidence on the use of laser as a therapeutic modality as compared to TURP reported similar functional results of bipolar-TURP, Thulium laser and Greenlight. For prostate gland ≤40 cc, HoLEP can be technically more difficult while Holmium-TUIP seems to be a valid option but with a higher rate of retrograde ejaculation which is considerably higher than the rate in electrocautery series. The diode laser showed excellent intra-operatively haemostasis with clear endoscopic vision and durable improvements in functional results, but may produce greater passive thermal energy conduction that can cause scrotal edema and anal pain. However, conclusions need to be drawn after median to long term evaluation of patients and consideration of the economic implications, coupled with the potential for reducing morbidity. Conclusions Evidence acquisition from the literature showed that mini-invasive surgeries, including Greenlight laser and Holmium laser incision represent valid alternatives to TURP in prostate ≤40 g. We reported effective results of laser therapy as therapeutic modalities as compared to TURP for the small prostate ≤40 mL, both for enucleation and excision or cauterization, however cost effective of laser in the current literature are still scarce and it should be implemented.

Botulinum toxin and nerve stimulation are viable options for overactive bladder refractory to pharmacotherapy. Treatment choice depends on multiple factors including associated symptoms, bladder function, and health economics. Decision-making should be individualised to the particular situation taking into account patient preference.

Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation.Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days.At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling.Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials.

Background Surgery for stress urinary incontinence (SUI) has been dominated recently by synthetic midurethral tapes. Increasing recognition of serious complications associated with nonabsorbable polypropylene mesh has led to resurgence in interest in alternative approaches, such as the autologous fascial sling (AFS). Despite being an efficacious and durable option in women with recurrent and complex SUI, there has been a reluctance to consider AFS in women with primary SUI due to a perception that it is only appropriate for treating patients with intrinsic sphincter deficiency (ISD) and is associated with high rates of urinary retention and de novo storage symptoms. Objective The video presented demonstrates the technique for a loosely applied midurethral AFS. In contrast to AFS applied at the bladder neck, this technical modification in patients who demonstrate primary SUI without ISD avoids high rates of de novo storage symptoms and urinary retention. Design, setting, and participants A retrospective review of data on patients undergoing AFS at a tertiary referral unit. Surgical procedure AFS placement in a "loose" fashion using a short length of fascia suspended on a suture bilaterally at the midurethral level rather than at the bladder neck and only using more tension in patients with ISD. Measurements Subjective cure rate, rates of postoperative storage symptoms, and urinary retention necessitating intermittent self-catheterisation (ISC). Results and limitations A total of 106 patients underwent AFS; the mean follow-up period was 9 mo. The mean age was 52.6 (range 24–83) yr. In total, 46.2% had primary SUI, whilst all of the remaining 53.8% had undergone prior surgical intervention. Overall subjective cure occurred in 79.2% of patients; a further 15.1% described significant subjective improvement in symptoms, whilst 5.7% reported no change in symptoms. In those with primary SUI, rates of subjective cure, improvement, and nonresolution of symptoms were 87.8%, 12.2%, and 0%, respectively. In individuals with prior surgical intervention, rates of subjective cure, improvement, and nonresolution of symptoms were 72.0%, 17.5%, and 10.5%, respectively. De novo storage symptoms occurred in 8.2% of those with primary SUI compared with 14.0% of those with prior surgical intervention. Only 2.0% patients with primary SUI needed to perform ISC beyond 2 wk compared with 10.5% of those after prior surgery. Conclusions A midurethral AFS appears to be effective and safe both in women with primary SUI who want to avoid the placement of permanent material and its attendant risks, and in more complex cases where this is less appropriate. Patient summary A graft taken from the covering of the abdominal muscle or the outer aspect of the thigh is an alternative to a synthetic vaginal mesh in women who have stress urinary incontinence requiring surgical treatment. Placing the graft loosely at the midpoint of the urethral tube, rather than at the bladder neck, reduces the risk of postoperative voiding difficulty and overactive bladder symptoms. Long-term data have suggested an outcome at least as good as a synthetic nonabsorbable tape without the potential for sling erosion into adjacent structures, as it avoids the use of nonabsorbable material.

Background Urethral strictures can be difficult to diagnose at an early stage because the urinary flow rate does not diminish until the urethral calibre is ≤3mm. In the past, posturethral surgery follow-up has relied upon flow rates and contrast imaging. Objective To evaluate the role of flexible urethroscopy in the follow-up of patients undergoing urethroplasty. Design, setting, and participants Prospective flexible urethroscopy follow-up of 144 male patients who underwent urethroplasty by a single surgeon over a 10-yr period at a tertiary referral centre. Intervention Flexible urethroscopy at 3, 6, and 12 mo postoperatively, and annually thereafter. Outcome measurements and statistical analysis Type of recurrence, based on urethroscopy findings, and further interventions were measured. Actuarial analysis was performed using Kaplan-Meier curves and a log-rank test. Results and limitations All 144 patients underwent flexible urethroscopy follow-up over a median postoperative follow-up of 22 mo (range: 1–96 mo). No further intervention was required for 117 patients (81.25%); 27 (18.75%) developed recurrences that required further treatment. Recurrences included diaphragms (13 patients) or significant restenosis (14 patients). Diaphragms were treated by urethrotomy, gentle dilatation, or a short course of intermittent self-dilatation. Restenosis required repeated simple procedures or surgical revision. Most recurrences (26 of 27, 96%) were detected within the first year. Urinary peak flow-rate data were available for 11 of 27 of these recurrences; 7 patients had flow rates >15ml/s. Anastomotic procedures had greater success than augmentation urethroplasty ( p =0.0136); there was no significant difference in outcomes between redo and non-redo surgery ( p =0.2093) Conclusions Endoscopic follow-up of patients after urethroplasty enables earlier identification and treatment of recurrences compared to the use of urinary flow rates alone. It also enables the identification of two different morphologic recurrence patterns that require different types of intervention. Patient summary Endoscopy detects most stricture recurrences within 1 yr after urethroplasty and is more sensitive than using urinary flow rates alone.

Pelvic fracture urethral injuries comprise one of the most challenging reconstructive procedures in urology. The obliterated or stenosed urethra can usually be effectively repaired by an end-to-end anastomosis (bulbomembranous anastomosis). To achieve this, a progression of surgical steps can be used to make a tension-free anastomosis. Before undertaking surgery it is important to comprehensively assess the patient to define their anatomical defects, in particular the site of the stenosis, the length of the distraction injury and the integrity of the bladder neck, and thus guide preoperative decision-making. Contemporary reports suggest that most pelvic fracture urethral distraction defects (PFUDD) can be adequately managed by a perineal approach. Nevertheless it is essential that all surgeons treating these injuries are familiar with the whole spectrum of operative steps that are necessary to repair PFUDD.

The recent International Consultation on Urological Disease (ICUD) panel 2010 confirmed that a urethral stricture is defined as a narrowing of the urethra consequent upon ischaemic spongiofibrosis, as distinct from sphincter stenoses and a urethral disruption injury. Whenever possible, an anastomotic urethroplasty should be performed because of the higher success rate as compared to augmentation urethroplasty. There is some debate currently regarding the critical stricture length at which an anastomotic procedure can be used, but clearly the extent of the spongiofibrosis and individual anatomical factors (the length of the penis and urethra) are important, the limitation for this being extension of dissection beyond the peno-scrotal junction and the subsequent production of chordee. More recently, there has been interest in whether to excise and anastomose or to carry out a stricturotomy and reanastomosis using a Heineke-Miculicz technique. Augmentation urethroplasty has evolved towards the more extensive use of oral mucosa grafts as compared to penile skin flaps, as both flaps and grafts have similar efficacy and certainly the use of either dorsal or ventral positioning seems to provide comparable results. It is important that the reconstructive surgeon is well versed in the full range of available repair techniques, as no single method is suitable for all cases and will enable the management of any unexpected anatomical findings discovered intra-operatively.

Purpose Autologous buccal mucosa is commonly utilized in the surgical treatment of urethral strictures. Extensive strictures require a larger quantity of tissue, which may lead to donor site morbidity. This review assesses progress in producing tissue engineered buccal mucosa as an alternative graft material. Results Few clinical studies have introduced cells onto biological or synthetic scaffolds and implanted resulting constructs in patients. The available studies show that buccal mucosa cells on acellular human dermis or on collagen matrix lead to good acute stage tissue integration. Urothelial cells on a synthetic substrate also perform well. However while some patients do well many years post-grafting, others develop stricture recurrence. Acellular biomaterials used to treat long urethral defects in animals commonly lead to fibrosis. Conclusions Tissue engineered buccal mucosa shows promise as a substitute for native tissue. The fibrosis which occurs months post-implantation may reflect the underlying disease process recurring in these patients.

Detrusor underactivity (DUA) is a poorly understood, yet common, bladder dysfunction, referred to as underactive bladder, which is observed in both men and women undergoing urodynamic studies. Despite its prevalence, no effective therapeutic approaches exist for DUA. Exactly how the contractile function of the detrusor muscle changes with ageing is unclear. Data from physiological studies in animal and human bladders are contradictory, as are the results of the limited number of clinical studies assessing changes in urodynamic parameters with ageing. The prevalence of DUA in different patient groups suggests that multiple aetiologies are involved in DUA pathogenesis. Traditional concepts focused on either efferent innervation or myogenic dysfunction. By contrast, contemporary views emphasize the importance of the neural control mechanisms, particularly the afferent system, which can fail to potentiate detrusor contraction, leading to premature termination of the voiding reflex. In conclusion, the contemporary understanding of the aetiology and pathophysiology of DUA is limited. Further elucidation of the underlying mechanisms is needed to enable the development of new and effective treatment approaches.

Synthetic non-degradable meshes used in pelvic floor surgery can cause serious complications such as tissue erosion. A repair material composed of an autologous oral fibroblast seeded degradable polylactic acid scaffold may be a viable alternative. The aims of this study were to investigate the effects of media supplementation with additives (ascorbic acid-2-phosphate, glycolic acid and 17-β-oestradiol) on the mechanical properties of these scaffolds. Oral fibroblasts were isolated from buccal mucosa. The effects of the three additives were initially compared in two-dimensional culture to select the most promising collagen stimulating additive. Sterile electrospun scaffolds were seeded with 500,000 oral fibroblasts and fixed in 6-well plates and subjected to ascorbic acid-2-phosphate (the best performing additive) and/or mechanical stimulation. Mechanical stimulation by fluid shear stress was induced by rocking scaffolds on a platform shaker for 1 h/day for 10 of 14 days of culture. In two-dimensional culture, ascorbic acid-2-phosphate (concentrations from 0.02 mM to 0.04 M) and glycolic acid (10 µM) led to significantly greater total collagen production, but ascorbic acid-2-phosphate at 0.03 mM produced the greatest stimulation (of the order of >100%). In three-dimensional culture, mechanical stimulation alone gave non-significant increases in stiffness and strength. Ascorbic acid-2-phosphate (0.03 mM) significantly increased collagen production in the order 280% in both static and mechanically stimulated scaffolds (p

Currently, underactive bladder, the symptom-based correlate of the urodynamic diagnosis of detrusor underactivity, has no effective drug treatments. Use of sympathomimetics, targeting cholinergic receptors, is not supported by current evidence. Several potential targets are the subject of ongoing investigation.

Urinary retention in women is an uncommon and poorly understood condition. In 1986, Fowler and colleagues described a syndrome in young women with unexplained urinary retention associated with polycystic ovary syndrome. The underlying abnormality was a poorly relaxing external urethral sphincter that when studied using concentric needle electromyography showed a distinct abnormal pattern suggesting direct spread of impulses between muscle fibres. These findings were subsequently reproduced by other researchers and in larger patient cohorts, but remain the subject of much debate. A poorly relaxing sphincter is thought to cause increased urethral afferent activity, which inhibits bladder afferent signalling leading to poor bladder sensation and detrusor underactivity. Most studies of Fowler's syndrome are limited due to small cohorts with no control group and a lack of videourodynamic data. Whether Fowler's syndrome represents a distinct cause of urinary retention or results from a maladaptive behaviour and is similar to dysfunctional voiding is unclear. Application of sacral neuromodulation in patients diagnosed with Fowler's syndrome can restore normal voiding, in the absence of any effective pharmacotherapy or surgical treatment.

submissions by geographic region. Hot at the ICS Meeting 2013 3 Neurourology and Urodynamics DOI 10.1002/nau bladder volume, and nociceptive behaviors. While both therapies may be some way off from routine practice, these data may open a route to early stage human trials. LUTS: INFECTION AND INFLAMMATION There is increasing recognition of inflammation and lowgrade infection as part of the pathophysiology of LUTS. Vijaya et al. (Abstract 123) demonstrated a significantly greater proportion of positive bacterial cultures in bladder biopsies from women with LUTS compared to asymptomatic women suggesting a link between bacterial infection and LUTS in women, however, therewas no significant association between women with recurrent UTI and positive biopsies. Similarly, Sorrentino et al. presented data demonstrating that in women without overt urinary tract infection, bacteriuria was associated with a range of LUTS (Abstract 126). Evidence of an inflammatory aetiology of OAB also was presented in a study by Gill et al. who demonstrated that women with OAB and pyuria of 1–9 cells/ml had significantly greater levels of two markers of urothelial inflammation (urinary lactoferrin and IL6) compared to controls (Abstract 124). This data suggests that contrary to the current literature, pyuria

Aims: Synthetic non-absorbable meshes are widely used to augment surgical repair of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however, there is growing concern such meshes are associated with serious complications. This study compares the potential of two autologous cell sources for attachment and extra-cellular matrix (ECM) production on a biodegradable scaffold to develop tissue engineered repair material (TERM). Methods: Human oral fibroblasts (OF) and human adipose-derived stem cells (ADSC) were isolated and cultured on thermo-annealed polyL-lactic acid (PLA) scaffolds for two weeks under either unrestrained conditions or restrained (either with or without intermittent stress) conditions. Samples were tested for cell metabolic activity (AlamarBlue 1 assay), contraction (serial photographs analyzed with image J software), total collagen production (Sirius red assay), and production of ECM components (immunostaining for collagen I, III, and elastin; and scanning electron microscopy) and biomechanical properties (BOSE tensiometer). Differences were statistically tested using two sample t-test. Results: Both cells showed good attachment and proliferation on scaffolds. Unrestrained scaffolds with ADSC produced more total collagen and a denser homogenous ECM than OF under same conditions. Restrained conditions (both with and without intermittent stress) gave similar total collagen production, but improved elastin production for both cells, particularly OF. The addition of any cell onto scaffolds led to an increase in biomechanical properties of scaffolds compared to unseeded scaffolds. Conclusions: OF and ADSC both appear to be suitable cell types to combine with biodegradablescaffolds,in thedevelopmentofa TERMfor thetreatmentofSUI andPOP.Neurourol.Urodynam. 33:531– 537, 2014. # 2013 Wiley Periodicals, Inc.

Urethral stricture disease affects many men worldwide. Traditionally, the investigation of choice has been urethrography and the management of choice has been urethrotomy/dilatation. In this review, we discuss the evidence behind the use of ultrasonography in stricture assessment. We also discuss the factors a surgeon should consider when deciding the management options with each individual patient. Not all strictures are identical and surgeons should appreciate the poor long-term results of urethrotomy/dilatation for strictures longer than 2 cm, strictures in the penile urethra, recurrent strictures, and strictures secondary to lichen sclerosus. These patients may benefit from primary urethroplasty if they have many adverse features or secondary urethroplasty after the first recurrence.

Context Stress urinary incontinence (SUI) is a common and bothersome problem that frequently requires operative management. Over the past two decades, novel techniques have been introduced into clinical practice. With the greater variety of surgical options now available, there is an increasing focus on selecting the appropriate procedure for the individual patient based on the likely underlying pathophysiologic mechanism. Objective To review the methods used in the evaluation of SUI and the proposed classification systems. Evidence acquisition A search of the PubMed database for the relevant search terms was conducted, and selected articles were retrieved and reviewed. Evidence synthesis Standardised terminology for the description of SUI has been produced by the International Continence Society describing the problem in terms of symptoms, clinical signs, and urodynamic observations. The two major pathophysiologic theories that have emerged over the past 50 yr, urethral hypermobility and intrinsic sphincteric deficiency, have influenced the development and adoption of surgical techniques. It is now recognised that these two entities are not dichotomous but often coexist. The primary aim of the evaluation of the patient presenting with SUI is to confirm the diagnosis and assess symptom severity before instituting conservative treatments. Secondary evaluation consists of more sophisticated techniques that assess anatomy of the bladder neck and urethra under rest and stress (eg, videourodynamics, ultrasound) or direct or indirect physiologic measures of the integrity of the sphincter mechanism. Conclusions Classification of patients with SUI into distinct groups based on probable pathophysiologic mechanism could help guide the choice of surgical procedure, but current systems are likely too simplistic, and methods of assessment lack standardisation in techniques and sensitivity. Patient summary Urinary leakage on exertion, termed stress incontinence , is a common problem that affects many women. There is a need to develop better ways of categorising the underlying causes of leakage to ensure that patients receive the optimal treatments.

The triad of leukoencephalopathy, cerebral calcifications, and ysts (LCC) represents a very rare, and distinct clinico-radiologic ntity of unknown etiology, first described in children by Labrune t al. [1] in 1996. The onset ranges from infancy to adults 1–5], with varying clinical presentations including a combinaion of mild cognitive dysfunction or normal intelligence, seizures, erebellar, pyramidal and extrapyramidal signs. The disorder s characterized by diffusely progressive basal ganglia, brain tem and subcortical white matter calcifications, cerebellar, and upratentorial parenchymal cysts, as well as diffusely abnormal 2-weighted sequences on MRI [1–4]. The white matter abnoralities were described as a leukoencephalopathy rather than demyelinating process (leukodystrophy) [2]. Histopathologic xamination reveals angiomatous-like blood vessels, gliosis, and eaded, corkscrew-shaped intracytoplasmic inclusions typically ssociated with highly gliotic tissue surrounding cysts and vascuar malformations (Rosenthal fiber formation) in the white matter 1,3,4]. Complications are typically a consequence of mass effect ncluding cerebral edema leading to intracranial hypertension, apilledema, syringomyelia and eventually tonsillar herniation [4].

Stromal derived factor-1 (SDF-1 or CXCL12) controls many aspects of stem cell function including trafficking and proliferation. Previously, it was demonstrated that DNA-damaging agents such as irradiation, cyclophosphamide or 5-fluorouracil increase the expression of SDF-1 by osteoblasts in murine marrow. Here, the production of SDF-1 by osteoblasts in vitro in response to cytokines known to be particularly important in bone physiology was examined using primary human osteoblasts (HOBs), mixed marrow stromal cells (BMSCs), and by, mouse, rat and human osteoblast-like cell lines. From these studies, it was determined that the expression of SDF-1 is an early feature of osteoblastic induction that may be modulated by IL-1beta, PDGF-BB, VEGF, TNF-alpha and PTH. Each of these factors increased SDF-1 synthesis, while TGF-beta1 decreased SDF-1 secretion. Of note, the biodistribution of SDF-1 in culture was equally distributed between the medium and detergent-soluble and -insoluble fractions of the cultures. Immunohistochemistry of developing bones demonstrated that SDF-1 was also a feature of early bone development first beginning in the perichondrium and moving into the marrow cavity of the developing bone analogue. As SDF-1 expression increases in response to PTH in vitro, animals were treated with an anabolic regime of PTH for 21 days. Under these conditions, significant increases in SDF-1 mRNA expression were observed near the growth plate and epiphysis regions of the long bones. Yet, in serum, immunodetectable SDF-1 levels were significantly reduced (24%) in the PTH-treated animals (Vehicle: 408 +/- 25 vs. PTH 308 +/- 20 SDF-1 pg/ml). Together, these data suggest a possible mechanism for localizing stem cells into a developing marrow where increased expression of SDF-1 in the local marrow environment along with decreased SDF-1 in the serum may create a homing gradient.

Since the early 1980swhen tissue-engineered skin for badly burned patients became a clinical reality [1], the field has progressed, and knowledge gained in one application has rapidly been applied to other clinical conditions. Thus it is now possible to produce several functionally competent epithelial tissues for transplantation, and our understanding of how to design tissues for particular applications is at an exciting stage. In this issue of the journal, the article by Orabi et al. [2] presents clear data in dogs that cell-free collagenous scaffolds do not work for extensive urethral defects. In contrast, if these scaffolds are preseeded with epithelial and stromal cells in the laboratory before implantation, then wide-calibre urethras can be achieved without strictures. We agree with the authors that more options are needed for patients with long defects of the urethra. Shorter defects can be handled successfully using the patient’s oral mucosa excised at the time of surgery. The preferred options are the cheek (buccal), followed by the ventral surface of the tongue (lingual) [3]. However, if the defect is extensive, securing adequate tissue is both difficult and associated with potential postoperative morbidity, and several groups are now engaged in exploring tissue-engineered alternatives. In designing tissue-engineered material to replace strictures of the urethra, a number of factors must be considered that are timely to review. One of the key questions in the overlapping fields of biomaterials, tissue engineering, and regenerative medicine is whether it is necessary to introduce cells onto a scaffold (whether the scaffold is natural or synthetic) to produce an effective repair. We suggest that this study helps clarify the debate about acellular scaffolds versus noncellular scaffolds. Whereas acellular scaffolds can have a role to play in small defects where one is relying on ingrowth of adjacent cells onto the scaffold, there is no evidence in the peer-reviewed literature of success in replacing large tissue defects in the urethra where the underlying problem is inevitably one of ischaemia of the corpus spongiosum [4]. We suggest there may be several combinations of both scaffolds and cells thatmay be useful. In the current study in dogs, the source of the natural decellularised scaffold was porcine bladder, and the source of the cells was autologous bladder biopsies from which bladder epithelial cells (urothelial cells) and bladder smooth muscle cells were cultured. Certainly allogeneic or xenogeneic bladder can provide a substrate that can support epithelial tissue reconstruction [5]. However, we suspect other natural collagenous or synthetic scaffolds will also prove viable and indeed present more attractive options in terms of safety, clinical convenience, and availability for patients and surgeons. In 2008 we reported on a 3-yr follow-up of the use of autologous tissue-engineered buccal mucosa for extensive substitution urethroplasty in five patients [6]. We found that initial results were good in all five, and at 3 yr, three patients had patent urethras based on the use of buccal epithelial cells and fibroblasts and decellularised acellular sterilised human dermis. Although these results are promising, synthetic scaffolds are in development that may offer an off-the-shelf reproducible and risk-free alternative to the use of donor human or animal collagen-based scaffolds. The Raya-Rivera group reported a study of five boys where a bladder biopsy was taken through a suprapubic incision from each patient, and the EU RO P E AN URO LOGY 6 3 ( 2 0 1 3 ) 5 3 9 – 5 4 1

To delineate the role of SDF-1 and CXCR4 in metastatic prostate cancer (CaP), positive correlations were established between SDF-1 levels and tumor metastasis. Neutralization of CXCR4 limited the number and the growth of intraosseous metastasis in vivo. Together, these in vivo metastasis data provide critical support that SDF-1/CXCR4 plays a role in skeletal metastasis. Introduction: Previously we determined that the stromal-derived factor-1 (SDF-1)/CXCR4 chemokine axis is activated in prostate cancer (CaP) metastasis to bone. To delineate the role of SDF-1/CXCR4 in CaP, we evaluated SDF-1 levels in a variety of tissues and whether neutralization of SDF-1 prevented metastasis and/or intraosseous growth of CaPs. Materials and Methods: SDF-1 levels were established in various mouse tissues by ELISA, immunohistochemistry, and in situ hybridization. To assess the role of SDF-1/CXCR4 in metastasis, bone metastases were established by administering CaP cells into the left cardiac ventricle of nude animals in the presence or absence of neutralizing CXCR4 antibody. The effect of SDF-1 on intraosseous growth of CaP cells was determined using intratibial injections and anti-CXCR4 antibodies and peptides. Results: There was a positive correlation between the levels of SDF-1 and tissues in which metastatic CaP lesions were observed. SDF-1 levels were highest in the pelvis, tibia, femur, liver, and adrenal/kidneys compared with the lungs, tongue, and eye, suggesting a selective effect. SDF-1 staining was generally low or undetectable in the center of the marrow and in the diaphysis. SDF-1 mRNA was localized to the metaphysis of the long bones nearest to the growth plate where intense expression was observed near the endosteal surfaces covered by osteoblastic and lining cells. Antibody to CXCR4 significantly reduced the total metastatic load compared with IgG control-treated animals. Direct intratibial injection of tumor cells followed by neutralizing CXCR4 antibody or a specific peptide that blocks CXCR4 also decreased the size of the tumors compared with controls. Conclusions: These data provide critical support for a role of SDF-1/CXCR4 in skeletal metastasis. Importantly, these data show that SDF-1/CXCR4 participate in localizing tumors to the bone marrow for prostate cancer.

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.

Purpose. To investigatein vivothe acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP).Methods. A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III.Results. Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds.Conclusions. The acutein vivoresponse to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues.

Gallstone ileus of the colon is an exceedingly rare cause of large-bowel obstruction. It is usually the result of fistula formation between the gallbladder and large bowel facilitating entry of the stone into gastrointestinal tract. Contrast enhanced abdominal computed tomography is an important diagnostic aid. Surgical management is the treatment of choice to prevent the disastrous complications of large-bowel obstruction. We describe the case of a 92-year-old man who presented with symptoms and signs of large-bowel obstruction. Radiological investigation showed a large gallstone impacted in the sigmoid colon. Open enterolithotomy was undertaken relieving the obstruction and the patient made a full recovery.

The assessment of men with bladder outflow obstruction relies on an adequate history and examination. Uroflowmetry and post-void residue estimation are very revealing and may be sufficient in the majority of men. The prostate-specific antigen test may be used to select men who are at a high risk of progression. In specific situations, cystometry may be required. We discuss the use of cystometry and the newer less-invasive methods of assessment that have emerged over the last few years, including ultrasound estimation of intravesical prostatic protrusion, prostatic urethra angle, detrusor wall thickness, ultrasound-estimated bladder weight, near-infrared spectroscopy and the condom catheter and penile cuff tests. Although these techniques show promise, they still require further modifications, standardization and testing in larger populations. In addition, they should be used in men where only specific questions need to be answered.