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To date, urethral stricture disease in men, though relatively common, represents an often poorly managed condition. Therefore, this article is dedicated to encompassing the currently existing data upon anatomy, etiology, symptoms, diagnosis, and treatment of the disease, based on more than 40 years of experience at a tertiary referral center and a PubMed literature review enclosing publications until September 2018.

Competing Interests: Competing interests: None declared.

Objectives: To describe the feasibility of a novel cell-based endoscopic technique using buccal epithelium, expanded and encapsulated in a thermoreversible gelation polymer scaffold for the treatment of urethral stricture., Methods: Six male patients with bulbar urethral stricture ranging from 2.0 to 3.5 cm in length were included in this pilot study. Autologous buccal epithelial cells from a small buccal mucosal biopsy were isolated, cultured and encapsulated in thermoreversible gelation polymer scaffold, and were implanted at the stricture site after a wide endoscopic urethrotomy., Results: All the patients voided well, with a mean peak flow rate of 24 mL/s. Urethroscopy carried out at 6 months showed healthy mucosa at the urethrotomy site. However, two of the six patients had recurrence at 18 and 24 months, respectively., Conclusions: This endoscopic-based Buccal epithelium Expanded and Encapsulated in Scaffold-Hybrid Approach to Urethral Stricture (BEES-HAUS) technique is a promising alternative for the open substitution buccal graft urethroplasty. It is possible to achieve the benefits of open substitution buccal urethroplasty with this endoscopic technique., (© 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: Though pediatric urethral stricture is an uncommon urological problem, it is a challenging urological one. The causative factors are iatrogenic, traumatic, and inflammatory. In the current study, the authors report their experience of the treatment of pediatric long anterior urethral stricture using penile circular fasciocutaneous flap., Patients and Methods: The study included 23 pediatric patients who had long anterior urethral strictures, which were repaired using circular penile fasciocutaneous flap. The flap was elevated through a subcoronal circumferential incision and then it was split ventrally. The strictured portion of the urethra was sharply incised ventrally, extending to 1 cm into normal urethra. The flap was sutured to the urethral plate over silicone catheter of suitable size, which was removed after 3 weeks. The follow-up was scheduled every 3 months for the first year and then yearly thereafter., Results: The urethroplasty was successful in 20 cases (86.96%). There were two cases complicated by stricture recurrence, which was managed by visual internal urethrotomy. Fistula formation was reported in one case and was repaired by simple excision and closure. Penile skin necrosis was reported in only one patient and was managed by frequent dressing., Discussion: During the last five decades, there was a substantial advancement in the reconstruction of long or complex anterior strictures due to the use of grafts and flaps. During pediatric urethral stricture repair, particular attention must be paid to the differences between adults and children anatomy, e.g. the small urethral lumen and tissue delicateness. McAninch introduced the reconstruction of complex anterior urethral strictures utilizing circular penile fasciocutaneous flap. The technique of penile fasciocutaneous flap urethroplasty takes long time and requires meticulous dissection. Therefore, it should be restricted for long or complex anterior urethra strictures. Success rate in this study was 86.96%, which is in the same league as that reported in literature as regard adults penile fasciocutaneous flap urethroplasty. Whitson et al. reported success rates of 84% and 79% in the 5th and 10th years, respectively. In another study, Kim et al. revealed a success rate of 68.9%. In this study, complications incidence was 21.6%, which is consistent with reported incidence of complications of adults penile fasciocutaneous flap urethroplasty (8%-20%)., Conclusion: According to the outcomes of this study, penile fasciocutaneous flap urethroplasty is a reasonable modality for the reconstruction of long anterior urethral stricture in pediatric patients especially after circumcision., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: The management of long ureteric strictures is very challenging, and ureteral substitution is necessary when end-to-end anastomosis can not be accomplished., Objective: To evaluate the mid-term results of laparoscopic appendiceal interposition pyeloplasty in children with long ureteric strictures., Methods: Between March 2010 and September 2016 four patients (median age 24 months, male/female 3/1) underwent laparoscopic appendiceal interposition pyeloplasty at the current hospital. Two patients had previously failed pyeloplasty, one had a traffic injury, and one had iatrogenic ureteral injury (Summary Table). The intraoperative, postoperative and follow-up results were analyzed. Success was defined as clinical (subjective) and radiologic (objective) resolution of the stricture., Results: All surgeries were successfully completed without conversion. The mean stricture length was 4.5 cm. Two cases were right-sided strictures, and two were left-sided. The mean operative time and estimated blood loss were 238.5 min and 25.0 ml, respectively. No intraoperative complication was encountered. No Grade 3 or Grade 4 complication was observed after surgery. One was anastomosed in the antiperistaltic manner and three were in the isoperistaltic fashion. The mean postoperative hospital stay was 7.3 days. The success rate was 100% at a mean follow-up duration of 33.8 months., Discussion: There is no consensus on the best surgical approach for long ureteric strictures. Ureteric replacement with intestinal segments or kidney autotransplantation is a viable alternative treatment to long ureteric strictures. However, both methods are technically challenging with significant complications. Appendiceal interposition to restore ureteral continuity has been described in adult patients. The current results demonstrated that laparoscopic appendiceal interposition pyeloplasty is a safe and feasible minimally invasive approach for the treatment of long ureteral strictures in children., Conclusions: Laparoscopic appendiceal interposition pyeloplasty was a viable minimally invasive alternative for children with long ureteric strictures on both left and right sides. Both isoperistaltic or antiperistaltic anastomosis were feasible., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: There is no standardized treatment algorithm for isolated fossa navicularis strictures and treatment modality often falls to surgeon preference. We evaluated the outcomes of a standardized algorithm for fossa navicularis strictures based on stricture etiology, lumen size, and glans size to minimize the number of patients requiring a two-stage urethral reconstruction., Materials and Methods: We retrospectively reviewed a prospectively maintained urethral reconstruction database by a single surgeon from 2011-2018. A treatment algorithm was applied and patients underwent one of three treatment modalities: a two-stage buccal mucosa graft (BMG), a single-stage dorsal inlay BMG, or a single-stage dorsal inlay BMG and ventral fasciocutaneous flap repair. Stricture recurrence was measured by inability to pass 17 Fr flexible cystoscope. Patient sexual function and satisfaction were evaluated by the International Index of Erectile Function (IIEF) and a patient perception questionnaire., Results: Forty-two patients met inclusion criteria with a mean follow up of 12.3 months. Urethroplasty success rate was 92%. There was no change in IIEF scores pre and postoperatively between single stage BMG, two-stage BMG, and combined BMG and flap repairs (+ 0.4; p = 0.88, 0.0; p = 1.00, and -0.3; p = 0.74). Ninety-four percent of patients reported being very satisfied or satisfied with their reconstruction., Conclusion: An algorithmic approach to the treatment of fossa navicularis strictures is an appropriate method for reconstructive intervention with a high rate of success and patient satisfaction with no significant impact on erectile function.

Purpose: We evaluated the management of recurrent bulbar urethral stricture disease after urethroplasty at our institution., Materials and Methods: We performed an institution review board approved, retrospective case study of our urethroplasty database to collect stricture related and postoperative information with an emphasis on bulbar urethral stricture disease recurrence after urethroplasty between 1996 and 2012. Repair types included primary anastomotic, augmented anastomotic and onlay repair. Recurrence, which was defined as the need for intervention, was diagnosed with cystoscopy or retrograde urethrogram., Results: We identified 437 men who underwent urethroplasty of bulbar urethral stricture disease as performed by 2 surgeons from January 1996 to December 2012. Of the men 395 had available followup data. Recurrence was identified in 25 men (6.3%), of whom all presented with symptoms, including a weak stream in 23, urinary tract infection in 1 and pyelonephritis in 1. Median time to recurrence was 10 months. Recurrence was initially treated endoscopically in 23 of 25 cases (92%), dilatation in 12 and visual urethrotomy in 11. In 5 patients (22%) further recurrence developed after endoscopic treatment, which was managed by repeat urethroplasty in 2, self-calibration only in 2 and visual urethrotomy with subsequent self-calibration in 1. We identified 2 distinct phenotypes of recurrent stricture, including type A-short focal recurrence, which may be salvaged with an endoscopic procedure, and type B-the long graft length type, which is less likely to be salvaged with endoscopy., Conclusions: Recurrence after urethroplasty is most likely to develop within the first 12 months. Type A short focal recurrence may be managed by a salvage endoscopic procedure, including dilation or visual urethrotomy. These data on the phenotype of recurrence may be useful for patient treatment., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared the results of initial buccal mucosal graft urethroplasty to the results of repeat and secondary cases of previous urethroplasty done by any technique other than buccal mucosal graft urethroplasty., Materials and Methods: We performed a retrospective study of patients who underwent buccal mucosal graft urethroplasty between January 2009 and December 2016 at a high volume center. Patients were stratified according to surgical sequence and characteristics were compared. We plotted Kaplan-Meier curves to compare stricture recurrence-free survival according to the surgical sequence. Multivariable Cox regression analyses were performed to delineate the impact of the surgical sequence on recurrence-free survival after adjusting for known clinical and surgical confounders., Results: Of 534 men with a median followup of 33 months (IQR 17-52) 436 (81.6%), 64 (12.0%) and 34 (6.4%) underwent an initial, a repeat and a secondary procedure, respectively. Patient characteristics were comparable (each p ≥0.2). Patients with reoperative procedures had received more previous endoscopic interventions and were more often operated on by high volume surgeons (each p ≤0.021). Operative time, graft length, stricture location and surgical techniques were comparable (each p ≥0.1). The success rate of initial, repeat and secondary procedures was 87.4%, 87.5% and 70.6%, respectively. On survival analyses patients who underwent secondary procedures fared worse than those who underwent repeat or initial procedures (p = 0.010). Similarly a secondary procedure was an independent risk factor for recurrence (HR 2.42, 95% CI 1.03-5.68, p = 0.043)., Conclusions: We found excellent results for repeat anterior 1-stage buccal mucosal graft urethroplasty, comparable to those of initial procedures. Patients who underwent secondary procedures were at higher risk for recurrence. However, when performed at a specialized center, the success rate was still high., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The treatment of complicated long segment strictures remains to a challenge, and the substitution urethroplasty treatment is often accompanied by subsequent tissue fibrosis and secondary stricture formation. In situ injection of human adipose tissue-derived stem cells (hADSC) could potential be applied for prevention of urethral fibrosis, but the cells transplantation alone may be insufficient because of the complicated histopathological micro-environmental changes in the injury site. This study investigated whether miR-21 modification can improve the therapeutic efficacy of ADSCs against urethral fibrosis to limit urethral stricture recurrence. MiR-21-modified ADSCs (miR-21) were constructed via lentivirus-mediated transfer of pre-miR-21 and GFP reporter gene. In vitro results suggested that miR-21 modification can increase the angiogenesis genes expression of ADSCs and enhance its anti-oxidative effects against reactive oxygen species (ROS) damage. In vivo results showed that miR-21 modification contributes to increased urodynamic parameters and better formation of the epithelium and the muscle layer as compared to ADSCs transplantation alone groups. The results demonstrated that miR-21 modification in ADSCs could improve urethral wound healing microenvironment, enhance stem cell survival through ROS scavenging and promote the neovascularization via regulating angiogenic genes expression, which eventually increase the ADSCs' therapeutic potential for urethral wound healing., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aims: Open surgery is the most commonly used methodological approach for generating a partial bladder outlet obstruction (pBOO) animal model. Surgical suturing closing a part of the urethral meatus induces comparable pathophysiological changes in bladder and renal functions, but the optimum degree of obstruction that closely mimics the clinical pathology of pBOO has not been elucidated. We investigated the optimum obstruction level by performing a comprehensive time-dependent analysis of the stability and reliability of this novel animal model., Methods: Six- to eight-week-old female BALB/c mice were divided into three groups according to the degree of urethral meatus stricture (UMS). Non-operated mice served as controls, and a pBOO model generated using the traditional method served as a positive control. A cystometric evaluation and long-term studies were performed to evaluate the validity and reliability of this novel animal model. An additional 35 mice were used to investigate the protein expression levels and histopathological features 24 h and 14 days postoperatively, respectively., Results: The characteristic cystometry features in the UMS group revealed increased changes in pressure-related parameters compared with the control. The 1/3 UMS model is an optional pBOO animal model because the cystometric evaluation and histopathological studies revealed a striking resemblance between the 1/3 UMS model and the model generated using the traditional open-surgery method., Conclusions: The minimally invasive UMS model required less time and produced minimal alterations in pathophysiologically relevant processes compared with the traditional surgery model. Suturing to cause UMS produced effective and repeatable patterns in bladder function investigations in mice., (© 2018 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.)

Objective: To compare postoperative outcomes between the perineal inverted-U and the vertical midline incision approaches of the urethroplasty and clarify them via gross anatomy., Patients and Methods: A total of 461 male patients, from Jan. 2006 to Jun. 2014, who underwent the urethroplasty via perineal midline vertical or inverted-U incision approach were recruited retrospectively. By match pairing for etiology and stricture length, 410 patients from two groups (205 for each group) were selected. Anatomy experiments were also performed. Outcome measurements and statistical analysis: the Chi-square, Student's t and binary logistic regression analyses were performed to compare the operative and postoperative data on the two groups., Results: With regard to patients with bulbar urethral stricture, the rate of surgical site infection (SSI) in perineal inverted-U group was 18.6% while 1.9% in the midline vertical group (p < 0.001). As for patients with posterior urethral stricture, the rate of SSI in the perineal inverted-U group was 16.4% while 3.1% in the midline vertical group (p = 0.001). Mean hospital stay between both groups were 15.8 ± 9.0 vs. 12.7 ± 3.8 days (p < 0.001). Anatomy experiments showed the number of damaged vessels and nerves involved in the inverted-U incision were approximately 1.6 to 2.0 folds more than the vertical midline, but the visual operation fields are similar between two approaches., Conclusions: The perineal midline vertical incision is a safer approach with fewer SSI and shorter hospital stay than the perineal inverted-U incision for bulbar and posterior urethroplasty.

Purpose: We investigated whether tissue engineered material may be adopted using standard techniques for anterior urethroplasty., Materials and Methods: We performed a retrospective multicenter study in patients with recurrent strictures, excluding those with failed hypospadias, lichen sclerosus, traumatic and posterior strictures. A 0.5 cm 2 oral mucosa biopsy was taken from the patient cheek and sent to the laboratory to manufacture the graft. After 3 weeks the tissue engineered oral mucosal MukoCell® graft was sent to the hospital for urethroplasty. Four techniques were used, including ventral onlay, dorsal onlay, dorsal inlay and a combined technique. Cystourethrography was performed 1 month postoperatively. Patients underwent clinical evaluation, uroflowmetry and post-void residual urine measurement every 6 months. When the patient showed obstructive symptoms, defined as maximum urine flow less than 12 ml per second, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as having treatment failure., Results: Of the 38 patients with a median age of 57 years who were included in study the strictures were penile in 3 (7.9%), bulbar in 29 (76.3%) and penobulbar in 6 (15.8%). Median stricture length was 5 cm and median followup was 55 months. Treatment succeeded in 32 of the 38 patients (84.2%) and failed in 15.8%. Success was achieved in 85.7% of ventral onlay, 83.3% of dorsal onlay, 80% of dorsal inlay and 100% of combined technique cases. No local or systemic adverse reactions due to the engineered material were noted., Conclusions: Our findings show that a tissue engineered oral mucosa graft can be implanted using the same techniques suggested for anterior urethroplasty and native oral mucosa, and guaranteeing a similar success rate., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess whether sclerosis in histology following bulbar urethroplasty is a predictive factor for failure of surgery., Materials and Methods: Resected stricture specimens from 45 patients undergoing open urethroplasty with excision and anastomosis were collected prospectively during 2011-2014. Histopathological characteristics, including fibrosis (grade I-III), inflammation and sclerosis, were evaluated using different routine staining. These specimens were compared to normal urethral resection specimens from patients undergoing sex-correction surgery. The uropathologist who conducted the analyses was blinded to the study design., Results: The outcomes of the histological classifications were as follows: 19 patients had grade I fibrosis, of whom three had failures; 13 patients had grade II fibrosis, without any failures; and the most severe fibrosis, grade III, including sclerosis, was found in 13 patients (11 with sclerosis), with failure in eight. Sclerosis was a significant risk factor for restricture when comparing patients with sclerosis and those without sclerosis, and likewise when adjusting for age, inflammation and stricture length., Conclusion: Histological findings of sclerosis in the resected urethral stricture specimen indicate a significantly higher risk for restricture after urethroplasty surgery.

Competing Interests: Competing interests: None declared.

Recurrent stenosis is the main reason inducing the failure of urethral stricture treatment. Our previous study has found that the 316L type Cu bearing stainless steel (316L-Cu SS) showed antimicrobial activity and anti-encrustation performance when it was used for relieving urethral obstructer. However, whether it can reduce the occurrence of fibrosis or not, we need further investigation to compare the cellular and molecular responses of human urethral scar fibroblast cells (USFCs) on 316L-Cu SS and medical grade 316L stainless (316L SS, as a control). [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)- 2H-tetrazolium (MTS) and Transwell were used to assess the cellular responses, which confirmed that 316L-Cu SS could inhibit proliferation and migration of USFCs. Molecular expressions of fibrosis were evaluated by western blot, real-time quantitative polymerase chain reaction (qPCR), and Cu/Zn superoxide dismutase (CuZnSOD) measurement. The results indicated that up-regulating of CuZnSOD attenuated the transforming growth factor-β1 expression and phosphorylation of Smad3 after exposure to 316L-Cu SS. Besides, the content of collagen type I (COL1) and collagen type III (COL3) secreting into the culture medium measured by enzyme-linked immunosorbent assay were in accord with the results of messenger ribonucleic acids. Both of them exhibited lower levels of COL1/COL3 exposure to 316L-Cu SS, demonstrating the inhibitory performance of 316L-Cu SS against fibrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2019-2028, 2018., (© 2017 Wiley Periodicals, Inc.)

Objective: To report our experience with anastomotic uretroplasty (AU) due to male urethral stricture disease (USD) and to identify factors affecting the results., Patients and Methods: We conducted a retrospective study over a period of 4 years and 6 months (July 2012 to December 2016). Any subsequent use of endoscopic urethrotomy or new urethroplasty was considered a failure., Results: Forty-eight cases were included. The mean age of patients was 53.5±17.3 years (23-87 years). Urinary retention was the reason for consultation in 42 cases (87.5%). The most common localization of USD was the bulbar urethra (n=45). The mean length of USD was 1.23±0.62cm (0.5-3cm) with a median length of 1cm. The etiology was post-infectious in 56.3% of cases. More than half (58.3%) of patients had already undergone at least one urethral manipulation. After an average follow-up of 21.1±12.6 months (1 to 52 months), the overall success rate was 77.1%. In univariate analysis, length, cause and location of the stricture, age of patient, the presenting symptoms of the stricture, previous urethral manipulation and surgeon experience did not significantly impact on the success rate of anastomotic urethroplasty at one and two years follow-up., Conclusion: The AU had provided good results in our practice. The infectious origin of the stricture and previous urethral manipulation did not significantly impact the result of this surgical technique., Level of Evidence: 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist., Materials and Methods: All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease., Results: There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007)., Conclusions: There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.

Objective: To develop an experimental model of anterior urethral stricture in rabbits using a bleomycin (BLM) injection technique., Materials and Methods: Thirty adult male New Zealand rabbits were randomly divided into 4 groups. In group 1 (BLM group), BLM was injected into the urethral submucosal tissue every other day through a catheter for 6 weeks at the 3-, 6-, 9-, and 12-o'clock positions of the urethra in 12 rabbits. In group 2 (phosphate-buffered saline [PBS] group), PBS was injected instead of BLM in 6 rabbits. In group 3 (stricture control group), an 8 × 20 mm urethral defect was created in 6 rabbits. In group 4 (normal group), 6 normal rabbits were included. All rabbits in the PBS group and stricture control group, as well as 6 rabbits in the BLM group, were sacrificed at 6 weeks. The remaining 6 rabbits in the BLM group were sacrificed at 10 weeks. Urethrography was performed in all rabbits before sacrifice, and the urethra was harvested for histologic analysis., Results: All rabbits in the BLM group showed mild urethral stricture at 4 weeks and significant urethral stricture at 6 weeks, without spontaneous resolution of the stricture at 10 weeks. No urethral stricture was observed in the PBS group at 4 and 6 weeks. Histologic examination confirmed the presence of fibrosis in the BLM group without spontaneous improvement., Conclusion: BLM injection can induce an experimental model of anterior urethral stricture in rabbits. This simple, highly efficient, reproducible method can be carried out in any laboratory., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To explore the etiology of male urethral stricture, analyze the therapeutic strategies of urethral stricture, and summarize the complicated cases.
 Methods: The data of 183 patients with urethral stricture were retrospectively analyzed, including etiology, obstruction site, stricture length, therapeutic strategy, and related complications.
 Results: The mean age was 49.7 years, the average course was 64.7 months, and the constituent ratio of 51 to 65 years old patients was 38.8% (71/183). The traumatic injury of patients accounted for 52.4% (96/183), in which the pelvic fracture accounted for 35.5% (65/183) and the straddle injury accounted for 16.9% (31/183). There were 54 cases of iatrogenic injury (29.5%). The posterior urethral stricture accounted for 45.9% (84/183), followed by the anterior urethral stricture (44.8%, 82/183) and the stenosis (6.6%, 12/183). A total of 99 patients (54.1%) received the end to end anastomosis, and 40 (21.9%) were treated with intracavitary surgery, such as endoscopic holmium laser, cold knife incision, endoscopic electroknife scar removal, balloon dilation, and urethral dilation. In the patients over 65-years old, the urethral stricture rate was 14.8% and the complication rate (70.4%) for transurethral resection of the prostate (TURP) was significantly higher than that of all samples (P<0.01).
 Conclusion: Both the etiology of male urethral stricture and the treatment strategy have changed and the incidence of traumatic and iatrogenic urethral stricture has increased in recent 3 years. The main treatment of urethral stricture has been transformed from endoscopic surgery into urethroplasty.

Pelvic fracture urethral distraction defect (PFUDD) seriously affects the quality of life of patients. At present, there are few effective drug treatments available for PFUDD‑induced urethral stricture, which is associated with fibrosis and scar formation in urethra lumen. Emerging evidence suggests that microRNAs (miRNAs/miRs) may be involved in the regulation of fibrosis, and analysis of miRNA expression profiles in urethral scar and normal urethra tissues may therefore benefit the discovery of novel treatments for urethral stricture with micro invasive procedures. In the present study, miRNA sequencing and quantitative polymerase chain reaction (qPCR) validation using paired scar and normal tissues from patients with PFUDD, and functional analysis of the miRNAs involved in the fibrosis associated signaling pathway was performed. A total of 94 differentially expressed miRNAs were identified in the scar tissue of patients with PFUDD. Among them, 26 miRNAs had significantly altered expression in the scar tissue compared with the normal tissue from the same patient. qPCR validation confirmed that miR‑129‑5p was overexpressed in scar tissue. The TGF‑β pathway‑associated functions of a total of 5 miRNAs (hsa‑miR‑129‑5p, hsa‑miR‑135a‑5p, hsa‑miR‑363‑3p, hsa‑miR‑6720‑3p and hsa‑miR‑9‑5p) were further analyzed, as well as their key molecular targets and functional mechanisms in signaling regulation. To conclude the miRNA sequencing indicated a significantly altered expression of hsa‑miR‑129‑5p, hsa‑miR‑135a‑5p, hsa‑miR‑363‑3p, hsa‑miR‑6720‑3p and hsa‑miR‑9‑5p in patients with PFUDD. These miRNAs and their potential target genes were associated with fibrosis in several diseases, and the data from the present study may help explore potential miRNA targets for future precision treatments for urethral stricture.

Objective: To assess the association of hypoandrogenism (HA) with urethral stricture disease in a series of patients undergoing urethroplasty at 2 institutions. HA has recently been associated with increased urethral atrophy in artificial sphincter failures and decreased androgen receptors and periurethral vascularity. HA might be an etiologic factor in urethral stricture disease., Methods: We reviewed the charts in 202 men with anterior urethral strictures between 2011 and 2017. We excluded patients with radiation-induced stricture, previous prostatectomy, previous urethroplasty, pelvic fracture-related strictures, or those on testosterone replacement. We defined HA by a total testosterone of less than 300 ng/dL. We used as age-matched cohort from a national database (National Health and Nutrition Examination Survey), as a reference. Stricture characteristics, such as length, location, and etiology were compared in HA and eugonadal groups., Results: Of 202 men with anterior urethral strictures, we excluded 45. Of the remaining 157 patients, 115 (73%) had preoperative testosterone measurements. Overall, hypoandrogenism (HA) was found in 65 of 115 (57%) men in the urethral stricture group compared with 28% of age-matched men in the national database. Mean stricture length in HA and eugonadal men was 7.2 cm and 4.8 cm, respectively (P = .02)., Conclusion: HA may be more prevalent and associated with increased disease severity in men with anterior urethral strictures. The relationship between HA and stricture formation and its potential impact on therapeutic outcomes merit further prospective investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: We examined the impact on urethral stricture complexity at urethroplasty of previous transurethral treatments such as dilation, urethrotomy and stenting, which are most commonly performed when treating male urethral stricture., Materials and Methods: We retrospectively reviewed the records of 45 males who had undergone transurethral treatments before urethroplasty. We compared urethrography findings at initial diagnosis with those at urethroplasty. Males with failed hypospadias repair, lichen sclerosis or a history of prior urethroplasty were excluded from analysis. We considered stricture complexity increased if the number and/or length of strictures on urethrography at urethroplasty was greater than that at initial diagnosis or false passage was newly identified., Results: Of the patients 39 (87%), 32 (71%) and 13 (29%) had undergone urethral dilation, urethrotomy and urethral stenting, respectively, and 39 (87%) had undergone repeat or multiple kinds of transurethral treatments. Stricture complexity was increased in 22 men (49%) while 7 (16%) required urethroplasty more complex than that anticipated from urethrography findings at initial diagnosis. Increased stricture complexity was significantly associated with a history of urethrotomy (p = 0.03), urethral stenting (p = 0.0002) and repeat transurethral treatments (p = 0.01). Multivariate analysis revealed that urethral stenting (p = 0.01) and repeat transurethral treatments (p = 0.01) were independent predictors of increased stricture complexity., Conclusions: Repeat transurethral treatments increase stricture complexity and are potentially counterproductive. Even a single application of temporary urethral stenting carries a high risk of complicating the stricture and requiring complex urethroplasty., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Balanitis xerotica obliterans (BXO) is a common condition that can affect the foreskin, glans, meatus, and urethra, and rarely can also involve urethra leading to stricture. Numerous procedures have been suggested to treat urethral stricture secondary to BXO but these have had variable results., Objective: We describe the first prospective study of a single stage buccal mucosal inlay grafting in children with urethral strictures resistant to existing remedies., Materials and Methods: We treated five boys with resistant urethral strictures secondary to BXO with a single stage buccal mucosal inlay graft (BMIG, Figure). Uroflowmetry was performed both pre- and post-operatively. Functional outcome was the prime measure determining success., Result: All the boys had a successful functional outcome and all expressed satisfaction with cosmetic outcome as well. Uroflow parameters improved remarkably, with maximum and mean urinary flow rates significantly improved from 4.2 mL/s to 26 mL/s (p = 0.0002) and from 1.6 mL/s to 12.2 mL/s (p = 0.003), respectively. Median follow-up was 34 months (range 30-42 months)., Discussion: This paper is the first to describe the successful use of buccal mucosal inlay grafts to treat refractory BXO stricture in children. Various surgical techniques have been proposed particularly in adults including single vs. staged procedures, preputial and post auricular grafts, circular mucosal buccal grafts, as well as double mucosal grafts placed both ventrally and dorsally. All of these procedures are not without problems, and had variable results and outcome. Most of the procedures have been described in adult urethra and are not suitable for paediatric small calibre urethra. Our technique of dorsal inlay graft gives a robust structure to the distal urethra avoiding diverticula, pooling or urine spraying and can be placed onto proximal urethra as well. We have not seen recurrence of BXO in our buccal grafts, which is reported in other grafts from prepuce and post auricular grafts. The number of patients presented in our study is limited, nonetheless an excellent result in all our cases makes this a compelling approach to manage BXO urethral strictures. An early intervention in such cases is paramount to convert a salvage operation to a pre-emptive procedure., Conclusion: A single stage buccal mucosal inlay grafting in children with BXO stricture can offer an excellent outcome., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Prior to urethral reconstruction many patients with stricture undergo a variable period during which endoscopic treatments are performed for recurrent obstructive symptoms. We evaluated the association among urethroplasty delay, endoscopic treatments and subsequent reconstructive outcomes., Materials and Methods: We reviewed the records of men who underwent primary bulbar urethroplasty from 2007 to 2014. Those with prior urethroplasty, penile and/or membranous strictures and incomplete data were excluded from analysis. Men were stratified by a urethroplasty delay of less than 5, 5 to 10 or greater than 10 years from diagnosis., Results: A total of 278 primary bulbar urethroplasty cases with complete data were evaluated. Median time between stricture diagnosis and reconstruction was 5 years (IQR 2-10). Patients underwent an average ± SD of 0.9 ± 2.4 endoscopic procedures per year of delay. Relative to less than 5 and 5 to 10 years a delay of greater than 10 years was associated with more endoscopic treatments (median 1 vs 2 vs 5), repeat self-dilations (13% vs 14% vs 34%), strictures longer than 2 cm (40% vs 39% vs 56%) and complex reconstructive techniques (17% vs 17% vs 34%). An increasing number of endoscopic treatments was independently associated with strictures longer than 2 cm (OR 1.06, p = 0.003), which had worse 24-month stricture-free survival than shorter strictures (83% vs 96%, p = 0.0003). Each consecutive direct vision internal urethrotomy was independently associated with the risk of urethroplasty failure (HR 1.19, p = 0.02)., Conclusions: Urethroplasty delay is common and often associated with symptomatic events managed by repeat urethral manipulations. Endoscopic treatments appear to lengthen strictures and increase the complexity of repair., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate clinical and patient-reported urinary and sexual outcomes after a long-segment stricture repair using the 1-sided urethral dissection, penile invagination, and dorsal buccal mucosa graft onlay technique described by Kulkarni et al., Methods: Patients from 4 institutions after single-stage repairs for long-segment urethral strictures (>8 cm) from January 2002 to April 2016 were reviewed. Technique described by Kulkarni et al was used in all cases. Clinical outcomes included uroflowmetry (Qmax) and post-void residuals. Patient-reported outcome measures included International Prostate Symptom Score survey, Sexual Health Inventory for Men, Male Sexual Health Questionnaire, and Global Response Assessment questionnaire to measure voiding, sexual, ejaculatory symptoms, and overall improvement, respectively., Results: Seventy-three patients with a minimum of 12 months' follow-up were included. The mean age and stricture length were 56 (21-80) years and 13.6 (8-21) cm, respectively. At a mean follow-up of 44 (12-162) months, 9 of 73 (12%) strictures recurred. The mean baseline International Prostate Symptom Score of 23 (7-24) decreased to 10 (1-17) on follow-up (P <.001). Eight of 42 patients (21.4%) reported an increase, and 6 of 42 patients (14.3%) decreased in Sexual Health Inventory for Men following urethroplasty. Ejaculatory function on Male Sexual Health Questionnaire improved after urethroplasty from 8 preoperatively to 11 postoperatively (P <.004). All patients reported improvement after urethroplasty on Global Response Assessment questionnaire. Post-void dribbling and chordee occurred in 45% and 25% of patients, respectively., Conclusion: Durable patency in most patients is demonstrated in this study. PROMs indicate an improvement in urinary function and moderate effect on sexual function. Transient penile chordee was evident in 25% of patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the surgical outcome and predictors of failure of substitution urethroplasty using either dorsal onlay buccal mucosal (BM) graft or ventral onlay penile skin flap (PS) for anterior urethral stricture ≥ 8cm., Patients and Methods: Between March 2010 and January 2016, 50 patients with anterior urethral stricture ≥ 8 cm were treated at our hospital. The surgical outcome and success rate were assessed. The predictors of failure were analyzed using multivariate analysis. Failure was considered when subsequent urethrotomy or urethroplasty were needed., Results: Dorsal onlay BM graft was carried out in 24 patients, while PS urethroplasty in 26 patients. There was no significant difference between both groups regarding patients demographics, stricture characteristics or follow-up period. One case in the BM group was lost during follow- up. Stricture recurrence was detected in 7 (30.4%) patients out of BM group while in 6 (23.1%) patients out of PS group (p value= 0.5). No significant differences between both groups regarding overall early and late complications were observed. Occurrence of early complications and the stricture length were the only predictors of failure in univariate analysis, while in multivariate analysis the occurrence of early complications was only significant., Conclusion: On short-term follow-up, both dorsal onlay BM graft and ventral onlay PS flap urethroplasty have similar success rates. However, BM graft has a potential advantage to reduce operative time and is also technically easier. The surgeon should avoid early local complications as they represent a higher risk for failure., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background/aim: To evaluate the effects of mesenchymal stem cell (MSC) therapy in an experimental bladder and posterior urethral injury model. Materials and methods: The study subjects consisted of 40 male Wistar albino rats that were divided into four groups: control group (n = 10) (the bladder was only surgically opened and closed), sham group (n = 10) (surgical procedure), IVMSC group (n= 10) (surgical procedure and intravenous MSC treatment), and LMSC group (n = 10) (surgical procedure and local MSC treatment). Histopathological evaluation was performed for the degree of fibrosis and inflammation and the extent and intensity of staining of vascular endothelial growth factor (VEGF) and endoglin (CD105). Results: There were no significant differences between the control and LMSC groups with respect to fibrosis (P = 0.070) or inflammation (P = 0.048). Fibrosis and inflammation were significantly lower in the IVMSC (P = 0.034 for fibrosis, P = 0.080 for inflammation) and LMSC (P = 0.01 for fibrosis, P = 0.013 for inflammation) groups when compared with the sham group. No significant differences regarding fibrosis and inflammation were observed between the IVMSC and LMSC groups (P = 0.198 for fibrosis, P = 0.248 for inflammation). A significant difference was noted between the sham and LMSC groups concerning VEGF staining intensity (P = 0.017). However, no significant difference was found among the groups with regard to the extent or intensity of CD105 staining (P > 0.05). Conclusion: MSC treatment significantly decreased the development of fibrosis in a uroepithelial injury model.

Aim: To evaluate the effectiveness of laparoscopic repair of primary strictures of ureteropelvic junction (UPJ) depending on baseline renal function of the ipsilateral kidney., Materials and Methods: The study analyzed results of 134 patients (78 women and 56 men, age from 18 to 56 years) who underwent various types of laparoscopic repair of the UPJ stricture from 2012 to 2015. Depending on the surgical technique all patients were divided into three groups: group 1 (n=34) underwent spiral flap technique by Culp and DeWeerd, group 2 (n=59) - Anderson-Hynes pyeloplasty and group 3 (n=41) had antevasal dismembered pyeloplasty. All interventions ended with internal ureteral stenting for up to 6-8 weeks. Also, all patients were divided into three subgroups, depending on the degree of renal function deficiency - less than 25%, 25-50%, and 51-75%. Treatment effectiveness criteria included the following parameters: complete relief of the pain syndrome, a decrease in the degree of pyeloectasia, stabilization or improvement of the functional state of the renal parenchyma (according to radioisotope renography), and the absence of recurrence of the UPJ stricture., Results: The overall effectiveness of UPJ laparoscopic reconstruction was 94.7% (127 of 134). The effectiveness of the treatment was independent of the surgical technique, the initial thickness of the renal parenchyma and the degree of PCS dilatation. There was an inverse correlation between the treatment effectiveness the degree of kidney function deficiency., Conclusion: In patients with hydronephrosis secondary to UPJ stricture, the effectiveness of surgical treatment is mainly determined by its timeliness. The best treatment results were observed in patients with better renal function. The degree of renal function deficiency should be considered the main prognostic factor for the effectiveness of the forthcoming operation.

Purpose: Until recently, tissue fibrosis-ultimately leading to permanent scaring-has been considered an irreversible process. However, recent findings indicate that it may be reversible after all. Vesicourethral anastomotic stenosis (VUAS) as fibrous narrowing is a frequent complication after radical prostatectomy with high recurrence rates and requires invasive treatment. The pathophysiology is poorly understood. Therefore, a combined mRNA and miRNA transcription profiling in tissue from VUAS was performed using nCounter technology., Methods: To assess tissue morphology and fiber composition, histochemical staining was performed. RNA expression of healthy and fibrotic tissue of twelve patients was analyzed using the human miRNA panel v3 and mRNA PanCancer pathway panel on the nCounter gene1 system and qRT-PCR. Differential expression data analysis was performed using the nSolver software implementing the R-based advanced pathway analysis tool. miRWalk2.0 was used for miRNA target prediction., Results: More linearized tissue architecture, increased collagens, and decreased elastic fibers were observed in VUAS samples. 23 miRNAs and 118 protein coding genes were differentially expressed (p < 0.01) in fibrotic tissue. miRNA target prediction and overlap analysis indicated an interaction of the strongest deregulated miRNAs with 29 deregulated mRNAs. Pathway analysis revealed alterations in DNA repair, cell cycle regulation, and TGF-beta signaling. qRT-PCR confirmed differential expression of top deregulated miRNAs and mRNAs., Conclusions: In VUAS tissue, severe alterations on mRNA and miRNA level are found. These consistent changes give insights into the pathogenesis of VUAS after radical prostatectomy and point to future options for transcriptomics-based risk stratification and targeted therapies.

Background: Harvest of oral mucosa for urethroplasty due to urethral stricture is associated with donor-site-morbidity. We assessed functionality and safety of an authorized tissue-engineered oral mucosa graft (TEOMG) under routine practice in stricture recurrences of any etiology, location, length and severity (real-world data)., Methods: 99 patients from eight centers with heterogenous urethroplasty experience levels were included in this prospective, non-interventional observational study. Primary and secondary outcomes were success rate (SR) and safety at 12 and 24months., Findings: All but one patient had ≥1, 77.1% (64 of 83)≥2 and 31.3% (26 of 83)≥4 previous surgical treatments. Pre- and postoperative mean±SD peak flow rate (Qmax) were 8.3±4.7mL/s (n=57) and 25.4±14.7mL/s (n=51). SR was 67.3% (95% CI 57.6-77.0) at 12 and 58.2% (95% CI 47.7-68.7) at 24months (conservative Kaplan Meier assessment). SR ranged between 85.7% and 0% in case of high and low surgical experience. Simple proportions of 12-month and 24-month SR for evaluable patients in all centers were 70.8% (46 of 65) and 76.9% (30 of 39). Except for one patient, no oral adverse event was reported., Interpretations: TEOMG is safe and efficient in urethroplasty., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Several factors such as genetic susceptibility, autoimmunity, hormones, infections, local trauma, urine, and occlusion have been speculated to play a role in the pathogenesis of lichen sclerosus. We report two male patients with lichen sclerosus around 'ectopic' urethral openings and the opposing surfaces of the penile shaft and scrotum, providing further evidence in support of urine and occlusion as contributing factors in the development of lichen sclerosus.

Background: The correlation between primary hypospadias repair and subsequent urethral strictures in adults has never been addressed., Objective: To evaluate the correlation between the site of primary hypospadias repair and the site of subsequent strictures and to investigate the predictive factors of failure after urethroplasty., Design, Setting, and Participants: An observational, retrospective, descriptive study of adult patients with urethral strictures following hypospadias surgery was carried out in a single centre., Intervention: Meatotomy, meatoplasty, end-to-end anastomosis, urethroplasty, perineostomy, urethrotomy, and fistula closure., Outcome Measurements and Statistical Analysis: We performed correlations between the site of primary hypospadias and the site of subsequent strictures, treatment failure, and patient lack of motivation for definitive treatment. Cross-tables, Kaplan-Meier curves, and logistic or Cox regression were used., Results and Limitations: A total of 408 patients, with median follow-up of 96 mo, were included. Concordance between the site of primary hypospadias repair and the site of subsequent strictures was observed. Multivariable analysis revealed that the number of previous operations needed for initial hypospadias repair was not associated with the risk of treatment failure (hazard ratio [HR] 0.96; 95% confidence Interval [CI] 0.88-1.04; p=0.3) or a lack of patient motivation (odds ratio 0.99, 95% CI 0.90-1.10; p=0.9). Length of stenosis (HR 1.38, 95% CI 1.11-1.71; p=0.004) and lichen sclerosus (HR 1.73, 95% CI 1.03-3.25; p=0.035) were associated with a higher risk of treatment failure. Our study is not representative of the entire population of patients with hypospadias repair., Conclusions: The stricture site is usually consistent with the site of hypospadias. Stricture length, but not the number of previous operations needed for primary hypospadias repair, was associated with the risk of failure., Patient Summary: The number of operations needed for hypospadias repair was not associated with failure of subsequent urethroplasty., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: A urethral stricture is a scar of the urethral epithelium which can cause obstructive voiding dysfunction with consequential damage of the upper urinary tract. Almost 45% of all strictures are iatrogenic; they develop in 2-9% of patients after radical prostatectomy, but can also occur after prostate cancer radiotherapy. This study provides 5‑year data of a certified prostate cancer center (PKZ) in terms of urethral strictures., Materials and Methods: Between 01/2008 and 12/2012 a total of 519 men were irradiated for prostate cancer (LDR and HDR brachytherapy as well as external beam radiation). The entire cohort was followed-up prospectively according to a standardized protocol (by type of irradiation). Short segment urethral strictures were treated by urethrotomy, recurrent and long segment stenosis with buccal mucosa urethroplasty., Results: A total of 18 of 519 (3.4%) patients developed a urethral stricture post-therapeutically, which recurred in 66% of cases after the first operative treatment. The largest risk for developing a urethral stricture is attributed to the HDR brachytherapy (8.9%)., Conclusion: Urethral strictures after prostate cancer radiotherapy should be diagnosed and treated in time for long-term preservation of renal function. The rate of radiogenic urethral strictures (3.4%) is equivalent to those after radical prostatectomy. Due to a high rate of recurrences, urethrotomy has a limited importance after irradiation.

Introduction: Panurethral stricture associated with lichen sclerosus is a therapeutic challenge. We present the analysis of our results using two urethroplasty techniques based on oral mucosa graft., Material and Method: Retrospective study in patients with long anterior urethral stricture (>8cm) associated with lichen sclerosus. Patients received urethroplasty with oral mucosa graft technique according Kulkarni (n=25) or two-step Johanson-Bracka urethroplasty (n=15). Demographics, operative time, complications (Clavien-Dindo), hospital stay, days with catheter, EAV postoperative pain, failure rate, need for retreatment and functional data including IPSS, QoL, Qmax, post void residual (PVR) are evaluated., Results: In all cases there was involvement of glandular and penile urethra, and in 75% of bulbar urethra. A single graft was used in 22.5%, two in 72.5% and three in 5%. Patients treated at a single step were younger (P=.007). Although the length of the stenosis was equivalent in both techniques (P=.96), relapse and complication rates were higher in two-step surgery (P=.05 and P=.03; respectively) and so was operative time (P<.0001) and overall stay (P=.0002). There were no differences in preoperative IPSS, QoL, Qmax or PVR, neither in postoperative values of IPSS or Qmax; but there was a difference in QoL (P=.006) and PVR (P=.03) favouring single-step urethroplasty. VAS pain on postoperative day 1 was also lower in Kulkarni urethroplasty than in the first step of Johanson-Bracka technique (P<.0001)., Conclusions: In patients with lichen sclerosus and long anterior urethral stricture Kulkarni urethroplasty provides more efficient and better patient reported outcomes than Johanson-Bracka urethroplasty. It also prevents cosmetic, sexual and voiding temporary deterioration inherent to 2-step surgery., (Copyright © 2016. Publicado por Elsevier España, S.L.U.)

Objectives: To review the long-term outcomes of transecting versus non-transecting urethroplasty to repair bulbar urethral strictures., Methods: A retrospective review was conducted of 342 patients who underwent anterior urethroplasty performed by a single surgeon from 2003 to 2014. Patients were excluded from further analysis if there had been prior urethroplasty, stricture location outside the bulbous urethra, or age <18 years. In the transecting group, surgical techniques used included excision and primary anastomosis and augmented anastomotic urethroplasty. In the non-transecting group, surgical techniques used included non-transecting anastomotic urethroplasty and dorsal and/or ventral buccal grafting. The primary endpoint was stricture resolution in transecting vs. non-transecting bulbar urethroplasty. Success was defined as freedom from secondary procedures including dilation, urethrotomy, or repeat urethroplasty., Results: One hundred and fifty-two patients met inclusion criteria. At a mean follow-up of 65 months (range: 10-138 months), stricture-free recurrence in the transecting and non-transecting groups was similar, 83% (n = 85/102) and 82% (n = 41/50), respectively (p = 0.84). Surgical technique (p = 0.91), stricture length (p = 0.8), and etiology (p = 0.6) did not affect stricture recurrence rate on multivariate analysis. There was no difference detected in time to stricture recurrence (p = 0.21)., Conclusions: In this retrospective series, transecting and non-transecting primary bulbar urethroplasty resulted in similar long-term stricture resolution rate. Prospective studies are needed to determine what differences may present in outcomes related to sexual function and long-term success.

Background: Little is known about the role of WNT signalling in pathological processes involving the urinary tract stroma. Here the impact of WNT signalling on bladder wall fibroblasts (BWFs) was studied using integrated expression profiling., Material and Methods: WNT ligand and downstream WNT pathway component expression was profiled in human BWFs using qRT-PCR. Highly expressed WNT2B was knocked down using siRNA in BWFs. The expression of 730 mRNAs and 800 miRNAs was analyzed on the nCounter MAX platform in #WNT2B and control transfected BWFs. qRT-PCR was used for validation in vitro and in matched scar and healthy bladder wall tissue samples of 12 patients with vesico-urethral anastomotic stricture (VUAS)., Results: Thirteen genes and 9 miRNAs showed differential expression in #WNT2B cells. Among these were TNFSF10, a key apoptosis inductor, (0.22fold, p = 0.011) and miR-1246 (36.2fold, p = 0.031). miRNA target prediction indicated TNFSF10 to be regulated by miR-1246. qRT-PCR analysis confirmed differential expression of miR-1246 and TNFSF10 in #WNT2B BWFs. Furthermore, TNFSF10 was significantly underexpressed in VUAS tissue (p = 0.009)., Conclusion: Perturbation of WNT signalling results in an altered expression of the apoptosis inductor TNFSF10. Similar changes are observed in VUAS. Further studies investigating the crosslink between WNT signalling and apoptosis regulation in the urinary tract stroma are warranted., (© 2017 S. Karger AG, Basel.)

Purpose: To investigate the surgical outcomes of dorsal onlay urethroplasty (DOU) using buccal mucosa graft (BMG) or penile skin graft (PSG) and to assess the effect of stricture length in men with anterior urethral strictures., Methods: A prospective cohort included men with anterior urethral strictures between 2008 and 2015. Patients underwent DOU using PSG or BMG. Patients had urethrography and uroflowmetry at 0, 3, 6, 12 months, and urethroscopy when needed. Student's t test, Mann-Whitney U tests, and Pearson's Chi-square test were used for analysis., Results: Sixty-nine patients (43 ± 14 year) were included, 31 received BMG, and 38 received PSG. Mean stricture length was 8 ± 3 cm, mean operative time was 145 ± 31 min, and mean follow-up was 56 ± 10 mo. Success rate was 87 % (90 % BMG vs. 84 % PSG, p = 0.4). Mean operative time was significantly shorter in PSG group (136 ± 29 min vs. 256 ± 58 min, p = 0.0005). Complications of grade I developed in 36 % (wound infection = 10 %, postvoiding dribbling = 18.8 %). Thirty of 69 patients (43 %) had strictures ≥8 cm, and 39 (57 %) had strictures <8 cm-success rate was equal for both subgroups (87 %). Mean blood loss, mean operative time, and incidence of postvoid dribbling were significantly lower in strictures <8 cm., Conclusion: BMG and PSG have comparable success rates in treatment of long anterior urethral strictures. Operative time is significantly longer in BMG. Long-segment strictures are associated with longer operative time, more blood loss, and more occurrence of postvoid dribbling. However, the length of the stricture has no influence on the success rate and functional outcomes of DOU.

The article presents a clinical case report of a stepwise correction of urethrovesical anastomotic stenosis and severe incontinence. At the first stage the authors performed re-urethrovesical anastomosis making the patient totally incontinent. At the second stage, an artificial sphincter was implanted.

Objective: To assess the effect of urethroplasty on overactive bladder (OAB) symptoms., Materials and Methods: From March 2011 to November 2014, 47 anterior urethroplasties were performed by a single surgeon (RSP). Of these, 42 men prospectively completed the validated Overactive Bladder Symptom Score (OABSS) prior to and after urethroplasty. Comparative analysis of preoperative to postoperative OABSS results was performed., Results: The median (range) age of men who comprised our cohort was 49 (22-90). Questionnaires were completed preoperatively and at a median of 12 months (2.3-74.6) postoperatively. Stricture location included the following: bulbar (75%), penile (15%), and membranous (7.5%) urethra. Median stricture length was 3 cm (1-6). Half of the men underwent an excision and anastomotic repair, and half underwent buccal mucosal graft. Men experienced significant improvement in urinary flow rate, postvoid residual urine, and OAB symptoms reported on the OABSS. Of the 28/42 men with preoperative, clinically significant OAB (ie, OABSS ≥ 8), 25/28 reported a 54.2% (0%-100%) median reduction in OABSS, with only 1 patient reporting worsening of symptoms following surgery. Those men with the highest preoperative OABSS experienced the greatest improvement in OAB symptoms postoperatively., Conclusion: In men with anterior urethral strictures and OAB, urethroplasty decreased reported OABSS by >50% and cured 90% of men with clinically significant OAB symptoms., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To describe the technique of ultrasound urethrogram (USUG) for the diagnosis of anterior urethral stricture performed in an ambulatory setting without any adjunctive imaging., Materials and Methods: Between September 2013 and September 2015, 35 consecutive adult men (>18 years old) presenting for anterior urethral reconstruction underwent outpatient USUG prior to definitive management. No alternative imaging test was performed. Lengths of the strictures as determined by outpatient USUG and via direct intraoperative measurements were compared by a paired t test., Results: Strictures were in the bulbar urethra in 24 men and in the penile urethra in 11 men. The differences between the outpatient USUG length measurements (mean = 1.86 cm) and the intraoperative stricture length measurements (mean = 2.02 cm) were not significantly different (P = .10). Additionally, the correlation coefficient between these length measurements was 0.84 (P < .001)., Conclusion: Preoperative USUG performed in the ambulatory setting for the diagnosis and characterization of anterior urethral strictures is safe and feasible. This outpatient imaging modality offers an alternative to retrograde urethrogram., (Published by Elsevier Inc.)

Purpose: Lichen sclerosus (LS) in men is poorly understood. Though uncommon, it is often severe and leads to repeated surgical interventions and deterioration in quality of life. We highlight variability in disease presentation, diagnosis, and patient factors in male LS patients evaluated at a tertiary care center., Materials and Methods: We retrospectively reviewed charts of male patients presenting to our reconstructive urology clinic with clinical or pathologic diagnosis of LS between 2004 and 2014. Relevant clinical and demographic information was abstracted and descriptive statistics calculated. Subgroup comparisons were made based on body mass index (BMI), urethral stricture, and pathologic confirmation of disease., Results: We identified 94 patients with clinical diagnosis of LS. Seventy percent (70%) of patients in this cohort had BMI >30 kg/m(2), and average age was 51.5 years. Lower BMI patients were more likely to suffer from urethral stricture disease compared to overweight counterparts (p=0.037). Patients presenting with stricture disease were more likely to be younger (p=0.003). Thirty percent (30%) of this cohort had a pathologic diagnosis of LS., Conclusions: Urethral stricture is the most common presentation for men with LS. Many patients endure skin scarring and have numerous comorbidities. Patient profile is diverse, raising the concern that not all patients with clinical diagnosis of LS are suffering from identical disease processes. The rate of pathologic confirmation at a tertiary care institution is alarmingly low. Our findings support a role for increased focus on pathologic confirmation and further delineation of the subtype of disease based on location and clinical manifestations.

Purpose: To investigate the effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture., Methods: Twenty-four adult New Zealand male rabbits underwent an electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Then rabbits were randomly divided into three groups: (1) normal control group: normal saline (NS), (2) the vehicle control group: dimethyl sulfoxide (DMSO), and (3) the treatment group: effective-dose rapamycin in DMSO (Ra), with 12, 6, and 6 rabbits in each group, respectively. Drugs were given by urethral irrigation daily for 4 weeks. Urethral tissue was harvested for histological and molecular analyses. TGFβ1 and MMP1 expression levels were evaluated by real-time quantitative PCR and immunohistochemistry., Results: Ten, six, and six rabbits were evaluated finally in Ra, DMSO, and NS group, respectively. Histological examination revealed the distribution of fibrosis and the degree of collagen deposition in the Ra group were smaller and slighter than the two control groups. Collagen content was significantly less in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). qRT-PCR analysis showed a higher expression of MMP1 mRNA in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). Immunohistochemistry showed the protein levels of MMP1 in the Ra group were significantly increased when compared with the DMSO group (P < 0.01) and the NS group (P < 0.01). On the other hand, no statistical difference could be found between every two groups in both mRNA and protein levels of TGFβ1., Conclusions: Rapamycin enhances the expression of MMP1 in a rabbit model of urethral stricture, but has no direct effect on the expression of TGFβ1.

The cause of posterior urethral valves (PUV) is unknown, but genetic factors are suspected given their familial occurrence. We examined cases of isolated PUV to identify novel copy number variants (CNVs). We identified 56 cases of isolated PUV from all live-births in New York State (1998-2005). Samples were genotyped using Illumina HumanOmni2.5 microarrays. Autosomal and sex-linked CNVs were identified using PennCNV and cnvPartition software. CNVs were prioritized for follow-up if they were absent from in-house controls, contained ≥ 10 consecutive probes, were ≥ 20 Kb in size, had ≤ 20% overlap with variants detected in other birth defect phenotypes screened in our lab, and were rare in population reference controls. We identified 47 rare candidate PUV-associated CNVs in 32 cases; one case had a 3.9 Mb deletion encompassing BMP7. Mutations in BMP7 have been associated with severe anomalies in the mouse urethra. Other interesting CNVs, each detected in a single PUV case included: a deletion of PIK3R3 and TSPAN1, duplication/triplication in FGF12, duplication of FAT1--a gene essential for normal growth and development, a large deletion (>2 Mb) on chromosome 17q that involves TBX2 and TBX4, and large duplications (>1 Mb) on chromosomes 3q and 6q. Our finding of previously unreported novel CNVs in PUV suggests that genetic factors may play a larger role than previously understood. Our data show a potential role of CNVs in up to 57% of cases examined. Investigation of genes in these CNVs may provide further insights into genetic variants that contribute to PUV., (© 2015 Wiley Periodicals, Inc.)

Objectives: The purpose of this study was to evaluate preoperatively the results of transrectal ultrasound (TRUS) in the detection of morphological, vascularization status of urethral rhabdosphincter (RS) and evaluate the correlation with urinary continence after radical prostatectomy (RP)., Methods: 211 patients who underwent RP were prospectively studied using TRUS scan of the RS thickness. At the end of the examination a study was performed with the use of colour-Doppler for the assessment of the RS vascularity pattern. The level of continence was graded on a 5 point scale as: 1 = complete continence, 2 = 1 pad daily, 3 = 2-3 pads daily, 4 = 4 or more pads daily, and 5 = complete incontinence., Results: It was possible to visualize the rhabdosphincter and its vascularity in all patients. Patients with normal continence (level 1 and 2) showed a sphincter-muscle thickness of 3.5 mm (± 0.4) and a hypoechoic ultrasound pattern. With respect to the other levels 3, 4 and 5 of urinary incontinence RS thickness was 2.8 mm (± 0.5), 2.1 mm (± 0.6), 1.7 (± 0.7) respectively. Incontinence after RP (≥ 3 level) was associated with urethral sphincter deficiency in the great majority of patients. Statistical significant differences were observed in the vascularity between continent and incontinent men in all measured vascularity variables (p &lt; 0.005)., Conclusions: This study suggests that RS integrity is a good predictor of urinary continence after RP and this information can be important during the preoperative phase as part of the informed consent.

The results of the perineal urethra plasty in 62 patients over its stricture and obliteration of the posterior portion after the pelvis bones fracture on 30 years were presented. In the early postoperative period complications occurred in 13 patients, in the long — recurrence of urethral stricture was observed in 8 (12.9%), of which 4 (6.5%) — reurethroplasty. Erectile dysfunction was detected in 19 (82.6%) patients.

Objective: To evaluate the mechanical property and biocompatibility of the Wnt pathway inhibitor (ICG-001) delivering collagen/poly(L-lactide-co-caprolactone) (P(LLA-CL)) scaffold for urethroplasty, and also the feasibility of inhibiting the extracellular matrix (ECM) expression in vitro and in vivo., Methods: ICG-001 (1 mg (2 mM)) was loaded into a (P(LLA-CL)) scaffold with the co-axial electrospinning technique. The characteristics of the mechanical property and drug release fashion of scaffolds were tested with a mechanical testing machine (Instron) and high-performance liquid chromatography (HPLC). Rabbit bladder epithelial cells and the dermal fibroblasts were isolated by enzymatic digestion method. (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) and scanning electron microscopy (SEM) were used to evaluate the viability and proliferation of the cells on the scaffolds. Fibrolasts treated with TGF-β1 and ICG-001 released medium from scaffolds were used to evaluate the anti-fibrosis effect through immunofluorescence, real time PCR and western blot. Urethrography and histology were used to evaluate the efficacy of urethral implantation., Results: The scaffold delivering ICG-001 was fabricated, the fiber diameter and mechanical strength of scaffolds with inhibitor were comparable with the non-drug scaffold. The SEM and MTT assay showed no toxic effect of ICG-001 to the proliferation of epithelial cells on the collagen/P(LLA-CL) scaffold with ICG-001. After treatment with culture medium released from the drug-delivering scaffold, the expression of Collagen type 1, 3 and fibronectin of fibroblasts could be inhibited significantly at the mRNA and protein levels. In the results of urethrography, urethral strictures and fistulas were found in the rabbits treated with non-ICG-001 delivering scaffolds, but all the rabbits treated with ICG-001-delivering scaffolds showed wide caliber in urethras. Histology results showed less collagen but more smooth muscle and thicker epithelium in urethras repaired with ICG-001 delivering scaffolds., Conclusion: After loading with the Wnt signal pathway inhibitor ICG-001, the Collagen/P(LLA-CL) scaffold could facilitate a decrease in the ECM deposition of fibroblasts. The ICG-001 delivering Collagen/P(LLA-CL) nanofibrous scaffold seeded with epithelial cells has the potential to be a promising substitute material for urethroplasty. Longer follow-up study in larger animals is needed in the future.

The goal of this study was to evaluate the effects of urethral reconstruction with a three-dimensional (3D) porous bacterial cellulose (BC) scaffold seeded with lingual keratinocytes in a rabbit model. A novel 3D porous BC scaffold was prepared by gelatin sponge interfering in the BC fermentation process. Rabbit lingual keratinocytes were isolated, expanded, and seeded onto 3D porous BC. BC alone (group 1, N  =  10), 3D porous BC alone (group 2, N  =  10), and 3D porous BC seeded with lingual keratinocytes (group 3, N  =  10) were used to repair rabbit ventral urethral defects (2.0   ×   0.8 cm). Scanning electron microscopy revealed that BC consisted of a compact laminate while 3D porous BC was composed of a porous sheet buttressed by a dense outer layer. The average pore diameter and porosity of the 3D porous BC were 4.23   ±   1.14 μm and 67.00   ±   6.80%, respectively. At 3 months postoperatively, macroscopic examinations and retrograde urethrograms of urethras revealed that all urethras maintained wide calibers in group 3. Strictures were found in all rabbits in groups 1 and 2. Histologically, at 1 month postoperatively, intact epithelium occurred in group 3, and discontinued epithelium was found in groups 1 and 2. However, groups 2 and 3 exhibited similar epithelial regeneration, which was superior to that of group 1 at 3 months (p  <  0.05). Comparisons of smooth muscle content and endothelia density among the three groups revealed a significant increase at each time point (p  <  0.05). Our results demonstrated that 3D porous BC seeded with lingual keratinocytes enhanced urethral tissue regeneration. 3D porous BC could potentially be used as an optimized scaffold for urethral reconstruction.

Objectives: To report our initial experience with urethra-sparing reconstruction combining dorsal preputial skin and ventral buccal mucosa grafts for tight bulbar urethral strictures., Methods: Between November 2006 and September 2012, 26 patients with tight bulbar strictures underwent urethroplasty. Using a ventral urethrotomy approach, the two-sided urethral reconstruction was carried out avoiding the transection of urethra and augmenting the preserved urethral plate by dorsal preputial skin plus ventral buccal mucosa grafts. The primary outcome was the objective urinary result, defined as the absence of stricture recurrence. The outcome was considered a failure when any postoperative instrumentation was required. Postoperative sexual dysfunctions were investigated using a validated questionnaire., Results: Mean follow up was 30.1 months (range 12-79 months). Mean stricture length was 3.3 cm (range 1.5-6 cm). Mean length for dorsal preputial skin and ventral buccal mucosa grafts was 3.2 cm (range 2-7 cm) and 4.9 cm (range 4-6 cm), respectively. Of 26 cases, 23 (88.5%) were successful and three (11.5%) were failures with stricture recurrence. Failures were treated with perineal urethrostomy in one case, ventral buccal graft urethroplasty in one case and internal urethrotomy in one case. Among 12 sexually active men preoperatively, none reported postoperative penile curvature/shortening, impaired erection or dissatisfaction regarding erection; sexual activity was unaltered pre- and post-surgery., Conclusions: In tight bulbar urethra strictures, the two-sided urethroplasty combining dorsal preputial skin and ventral buccal mucosa grafts provides a safe and effective semi-circumferential reconstruction by augmenting the preserved urethral plate, with no impact on sexual function., (© 2015 The Japanese Urological Association.)