Therapeutic Potential of Human Adipose-Derived Stem Cell Exosomes in Stress Urinary Incontinence - An in Vitro and in Vivo Study.

BACKGROUND/AIMS: To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model. METHODS: For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (n = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses. RESULTS: The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. CONCLUSIONS: Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI.

Three-Dimensional Computerized Model Based on the Sonourethrogram: A Novel Technique to Evaluate Anterior Urethral Stricture.

PURPOSE: The sonourethrogram is a useful alternative to the traditional retrograde urethrogram to evaluate anterior urethral strictures. With the development of 3-dimensional reconstructive techniques 3-dimensional urethral imaging can provide more accurate and useful information to enable the surgeon to make the best surgical decisions. We evaluated the accuracy and efficacy of a 3-dimensional reconstructed digital model of the urethra based on the sonourethrogram to assess anterior urethral disease. MATERIALS AND METHODS: A total of 50 patients with an anterior urethral stricture and 10 healthy volunteers were enrolled in this study from April 2014 to January 2017. All patients and volunteers underwent sonourethrogram and retrograde urethrogram. Three-dimensional urethral models were reconstructed based on the sonourethrogram. Stricture length and location on retrograde urethrogram or sonourethrogram based images were compared with those found at operation. RESULTS: The 3-dimensional digital model revealed the entire anterior urethra, including the navicular fossa, and the penile and bulbar parts. The semitransparent model clearly demonstrated the structure of the corpus spongiosum and inside the urethral lumen. Further information on spongiofibrosis could also be seen in the 3-dimensional digital model. There was no significant difference in stricture length or location in the 3-dimensional model compared with retrograde urethrogram imaging and actual surgical findings. However, the latest technique could only reconstruct the short segment of the anterior urethra due to the probe width limitation. CONCLUSIONS: The 3-dimensional computerized model based on the sonourethrogram is a novel and effective technique of evaluating anterior urethral strictures.

Intermediate-Term Outcomes and Complications of Long Segment Urethroplasty with Lingual Mucosa Grafts.

PURPOSE: We evaluated outcomes and donor site complications in male patients with complex urethral strictures who underwent urethroplasty using with long strip oral mucosal grafts. We also analyzed whether a lingual mucosa graft is a good substitute for repairing long segment urethral strictures. MATERIALS AND METHODS: This retrospective study was done in 81 male patients with complex urethral strictures who underwent oral mucosal graft urethroplasty. Patients with long segment (8 cm or greater) anterior urethral strictures who were considered candidates for long strip lingual mucosa graft urethroplasty were included in study. RESULTS: Oral mucosal graft urethroplasty was performed in 81 patients with complex urethral strictures between August 2006 and December 2014. Mean urethral stricture length was 12.1 cm (range 8 to 20). A single 9 to 12 cm long strip lingual mucosa graft was used in 52 patients, a lingual mucosa graft greater than 12 cm was placed in 17 and a lingual mucosa graft combined with a buccal mucosal graft was used in 12. Mean followup was 41 months (range 15 to 86) postoperatively. The overall urethroplasty success rate was 82.7%. Urethral complications developed in 14 patients (17.3%), including urethral strictures in 10 and urethrocutaneous fistulas in 4. At 12 months 5 patients (6.2%) reported minimal difficulty with fine motor movement of the tongue. CONCLUSIONS: Lingual mucosa harvested from the ventrolateral surface of the tongue can provide a wide and long graft that is an excellent urethral substitute. Donor site complications are primarily limited to postoperative year 1. Our study confirms that the lingual mucosa graft is a good substitute for urethral reconstruction and lingual mucosa graft urethroplasty is a valuable procedure to treat long anterior urethral strictures.

Single-Staged Improved Tubularized Preputial/Penile Skin Flap Urethroplasty for Obliterated Anterior Urethral Stricture: Long-Term Results.

INTRODUCTION: To present an improved tubularized flap (ITF) technique and report the outcome of single-stage urethroplasty using preputial/penile skin flaps (PSFs) for the treatment of obliterative anterior urethral strictures (AUSs). MATERIALS AND METHODS: From January 2000 to June 2012, 42 cases of obliterative AUS (3-14 cm, mean 6.38 cm) with urethral plate unsalvageable were treated using PSF-ITF urethroplasty including longitudinal skin flap, circular island flap, L-flap, Q-flap. Patients were divided into 3 groups: pendulous urethral stricture (Group A), bulbar urethral stricture (Group B) and panurethral strictures (Group C). Patients were followed up by uroflowmetry, urethrography and ureteroscope when necessary. RESULTS: The mean follow-up in these patients was 65 months (range 36 months-15 years). The primary success rates at 3-year follow-up were 75, 75 and 60% for Groups A, B and C, respectively. The overall success rates were 85, 83 and 70% with the remedial measure of a single visual internal urethrotomy at 3-year follow-up. A total 60% of the patients in the study completed more than 5 years of follow-up with no additional recurrence. CONCLUSIONS: Improved tubularized preputial/PSF urethroplasty with relatively high overall satisfaction is a novel technique for treatment of AUS when there is inadequate urethral plate or obliterative defects.

Etiology and Management of Male Iatrogenic Urethral Stricture: Retrospective Analysis of 172 Cases in a Single Medical Center.

PURPOSE: To investigate the etiology and management of male iatrogenic urethral stricture in China. METHODS: The data of 172 patients with iatrogenic urethral stricture who underwent treatment at a high volume reference center in China from January 2008 to February 2014 were analyzed retrospectively. Databases were analyzed to understand the impact of different types of iatrogenic injury on stricture location, length and treatment of urethral strictures, as well as success rates. RESULTS: The most common type of iatrogenic stricture was urethral instrumentations in 80 patients (46.51%). Mean stricture length was 3.3 ± 2.54 cm and the longest strictures were those caused by intravesical instillation. Substitution urethroplasty was the most common intervention and was performed in 60.47% (104/172) of patients. The overall success rate was 85.00% (136/160). Univariable analyses revealed that the type of iatrogenic injury was significantly related to restenosis (p = 0.036), and it is more apt to postoperative restenosis in the type of intravesical instillation than others. CONCLUSION: Our results showed that urethral instrumentation is the most common etiology of iatrogenic urethral stricture, and most iatrogenic urethral strictures involve the anterior urethra. The different etiologies are closely associated with stricture location, length and the overall prognosis of urethral strictures.

Curcumin inhibits growth of prostate carcinoma via miR-208-mediated CDKN1A activation.

Prostate cancer (PC) is a prevalent cancer in aged men. Curcumin is an active ingredient that has been extracted from the rhizome of the plant Curcuma longa. Recently, a potential of Curcumin against PC has been reported in PC, whereas the underlying molecular mechanisms are not completely understood. Here, we studied the effects of low-dose Curcumin on PC cell growth. Curcumin (from 0.2 to 0.8 µmol/l) dose-dependently inhibited the proliferation of PC cells, without affecting cell apoptosis. Further analyses showed that Curcumin dose-dependently increased a cell cycle suppressor CDKN1A at protein levels, but not mRNA levels, in PC cells, suggesting that Curcumin may regulate the translation of CDKN1A, as well as a possible involvement of miRNA intervention. From all CDKN1A-3'-UTR-binding miRNAs, we found that miR-208 was specifically inhibited in PC cells dose-dependently by Curcumin. Moreover, miR-208 was found to bind CDKN1A to suppress its expression. In a loss-of-function experiment, PC cells that overexpressed miR-208 failed to decrease cell proliferation in response to Curcumin. Together, these data suggest that Curcumin inhibits growth of PC via miR-208-mediated CDKN1A activation.

Changing trends in the causes and management of male urethral stricture disease in China: an observational descriptive study from 13 centres.

OBJECTIVE: To determine whether there have been any changes in the causes and management of urethral strictures in China. PATIENTS AND METHODS: The data from 4,764 men with urethral stricture disease who underwent treatment at 13 medical centres in China between 2005 and 2010 were retrospectively collected. The databases were analysed for the possible causes, site and treatment techniques for the urethral stricture, as well as for changes in the causes and management of urethral strictures. RESULTS: The most common cause of urethral strictures was trauma, which occurred in 2,466 patients (51.76%). The second most common cause was iatrogenic injures, which occurred in 1,643 patients (34.49%). The most common techniques to treat urethral strictures were endourological surgery (1,740, 36.52%), anastomotic urethroplasty (1,498, 31.44%) and substitution urethroplasty (1,039, 21.81%). A comparison between the first 3 years and the last 3 years showed that the constituent ratio of endourological surgery decreased from 54% to 32.75%, whereas the constituent ratios of anastomotic urethroplasty and substitution urethroplasty increased from 26.73% and 19.18% to 39.93% and 27.32%, respectively (P < 0.05). CONCLUSIONS: During recent years, there has been an increase in the incidence of urethral strictures caused by trauma and iatrogenic injury. Endourological urethral surgery rates decreased significantly, and open urethroplasty rates increased significantly during the last 3 years.

Factors that influence the outcome of open urethroplasty for pelvis fracture urethral defect (PFUD): an observational study from a single high-volume tertiary care center.

PURPOSE: To report the clinical features of pelvic fracture urethral injury (PFUI) and assess the real effect of factors that are believed to have adverse effects on delayed urethroplasty. METHODS: An observational descriptive study in a single urological center examined 376 male patients diagnosed with PFUI who underwent open urethroplasty from 2009 to 2013. Analyzed factors included patient age at the time of injury, etiology of PFUI, type of emergency treatment, concomitant injuries, length and position of stricture, type of urethroplasty and the outcome of surgery. Univariate and multivariate logistic regression analyses were applied, together with analytical statistic methods such as t test and Chi-square test. RESULTS: The overall success rate of delayed urethroplasty was 80.6 %. Early realignment was associated with reduced stricture length and had beneficial effect on delayed surgery. Concomitant rectum rupture, strictures longer than 1.6 cm and strictures closer than 3 cm to the bladder neck were indicators of poor outcome. Age, type of injury, urethral fistula and bladder rupture were not significant predicators of surgery outcome. Failed direct vision internal urethrotomy and urethroplasty had no significant influence on salvage operation. CONCLUSIONS: The outcome of posterior urethroplasty is affected by multiple factors. Early realignment has beneficial effect; while the length and position of stricture and its distance to bladder neck plays the key role, rectum rupture at the time of injury is also an indicator of poor outcome. The effect of other factors seems insignificant.

Therapeutic potential of human umbilical cord blood mesenchymal stem cells on erectile function in rats with cavernous nerve injury.

OBJECTIVE: To evaluate the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCBMSCs) on promoting erectile function in a rat model of bilateral cavernous nerve (CN) crush injury. RESULTS: Fifty male Sprague-Dawley rats were randomly assigned to sham + PBS group (n = 10), BCNI (bilateral cavernous nerve crush injury) + PBS group (n = 10), BCNI + hUCBMSCs group (n = 30). At day 28 (n = 10) post-surgery, erectile function was examined and histological specimens were harvested. Compared with BCNI + PBS group, hUCBMSC intracavernous injection treatment significantly increased the mean ratio of ICP/MAP, nNOS-positive nerve fibers in the dorsal penile nerve, smooth muscle content, and smooth muscle to collagen ratio in the corpus cavernousum. Electron microscopy revealed few CN and major pelvic ganglion (MPG) lesions in the BCNI + hUCBMSCs group. Injected hUCBMSCs were localized to the sinusoid endothelium of the penis and MPG on day 1, 3, 7, and 28 post-intracavernous injection. CONCLUSION: hUCBMSCs intracavernous injection treatment improves erectile function by inhibiting corpus cavernosum fibrosis and exerting neuroregenerative effects on cell bodies of injured nerves at MPG in a BCNI rat model.

Crosstalk between TGF-ß1 and CXCR3 signaling during urethral fibrosis.

Urethral fibrosis is an important pathological feature of urethral stricture. TGF-ß1 and CXC chemokine receptor 3 (CXCR3) signaling have been reported as the critical pathways involved in the pathology of fibrosis. Here, we collected the urine samples from the patients with recurring urethral stricture, recurring stricture treated by cystostomy, and age- and gender-matched healthy people. ELISA detection revealed that TGF-ß1 level was significantly up-regulated for the urethral stricture patients. By contrast, flow cytometry, real-time PCR detection, and immunofluoresecent staining showed that urethral stricture resulted in decreased expression of CXCR3. TGF-ß1 treatment could increase cell proliferation and migration ability of urethra fibroblasts, whereas IP-10/CXCR3 signaling showed the opposite effect. Further, we found a crosstalk between TGF-ß1 and CXCR3 signaling in the regulation of urethral fibrosis. Thus, pharmacological intervention of TGF-ß1 or CXCR3 signaling has a potential as the therapeutic target for the prevention of urethral fibrosis.

Electrocautery-induced cavernous nerve injury in rats that mimics radical prostatectomy in humans.

OBJECTIVE: To investigate the early and delayed effects of cavernous nerve electrocautery injury (CNEI) in a rat model, with the expectation that this model could be used to test rehabilitation therapies for erectile dysfunction (ED) after radical prostatectomy (RP). MATERIALS AND METHODS: In all, 30 male Sprague-Dawley rats were randomly divided equally into two groups (15 per group). The control group received CNs exposure surgery only and the experimental group received bilateral CNEI. At 1, 4 and 16 weeks after surgery (five rats at each time point), the ratio of maximal intracavernosal pressure (ICP) to mean arterial pressure (MAP) was measured in the two groups. Neurofilament expression in the dorsal penile nerves was assessed by immunofluorescent staining and Masson's trichrome staining was used to assess the smooth muscle to collagen ratio in both groups. RESULTS: At the 1-week follow-up, the mean ICP/MAP was significantly lower in the CNEI group compared with the control group, at 9.94% vs 70.06% (P < 0.05). The mean ICP/MAP in the CNEI group was substantially increased at the 4- (35.97%) and 16-week (37.11%) follow-ups compared with the 1-week follow-up (P < 0.05). At all three follow-up time points, the CNEI group had significantly decreased neurofilament staining compared with the control group (P < 0.05). Also, neurofilament expressions in the CNEI group at both 4 and 16 weeks were significantly higher than that at 1 week (P < 0.05), but there was no difference between 4 and 16 weeks (P > 0.05). The smooth muscle to collagen ratio in the CNEI group was significantly lower than in the control group at the 4- and 16-week follow-ups (P < 0.05), and the ratio at 16 weeks was further reduced compared with that at 4 weeks (P < 0.05). CONCLUSIONS: In the CNEI rat model, we found the damaging effects of CNEI were accompanied by a decline in ICP, reduced numbers of nerve fibres in the dorsal penile nerve, and exacerbated fibrosis in the corpus cavernosum. This may provide a basis for studying potential preventative measures or treatment strategies to ameliorate ED caused by CNEI during RP.

Tissue-engineered buccal mucosa using silk fibroin matrices for urethral reconstruction in a canine model.

BACKGROUND: To investigate the feasibility of urethral reconstruction using tissue-engineered buccal mucosa (TEBM) with silk fibroin (SF) matrices in a canine model. MATERIALS AND METHODS: Autologous oral keratinocytes and autologous fibroblasts were isolated, expanded, and seeded onto SF matrices to obtain TEBM. The TEBM was assessed using hematoxylin and eosin staining and scanning electron microscopy. A 5-cm urethral mucosal defect was created in 10 female canines. Urethroplasty was performed using TEBM in five canines in the experimental group and with SF matrices without cells in the five canines in the comparison group. Retrograde urethrography was performed after 6 mo of grafting. The urethral grafts were analyzed grossly and histologically. RESULTS: The oral keratinocytes and fibroblasts exhibited good biocompatibility with the SF matrices. TEBM could be constructed using SF matrices. The canines implanted with the tissue-engineered mucosa voided without difficulty. The retrograde urethrography revealed no sign of stricture. The histologic staining showed that epithelial cells developed gradually and exhibited stratified epithelial layers at 6 mo. In the comparison group, the canines had difficulty voiding, and the retrograde urethrography showed urethra stricture. The histologic staining showed that one to two layers of epithelial cells developed. CONCLUSIONS: The TEBM using SF matrices could be a potential material for urethra reconstruction.

Complete androgen insensitivity syndrome in juveniles and adults with female phenotypes.

AIM: To report on six cases of the diagnosis and treatment of patients with complete androgen insensitivity syndrome (CAIS) and a review of the relevant published work. METHODS: A retrospective analysis was performed on the clinical features, diagnosis and treatment of a total of six patients with CAIS who were admitted to our hospital between September 1985 and June 2012. All surgical patients were examined for sex chromosomes and sex hormone levels pre- and postoperatively, respectively, and underwent lower abdominal B ultrasounds and pathological examinations among other tests. RESULTS: Five of the patients were treated with castration, one patient aged 5 years was treated conservatively Tissue from surgical resections showed normal testicular tissue that comprised Leydig cells and Sertoli cells, and pathological examinations showed no sign of testicular cancer. Following corrective operations, postoperative complications, such as female secondary sexual characteristics, stagnation and osteoporosis, have not developed. Sex hormone level ratio changed significantly after being treated with castration compared with preoperative levels; mainly testosterone and estrogen decreased significantly (P < 0.05), while luteinizing hormone and follicle-stimulating hormone significantly increased (P < 0.05). However, prolactin did not change significantly (P > 0.05). CONCLUSION: The study show that removal of the testes in CAIS patients after puberty is safe and reliable. Meanwhile, it is essential to provide a hormone drug after being treated with castration. Further studies are needed to evaluate the safety and the quality of life for CAIS patients.

Optimizing anterior urethral stricture assessment: leveraging AI-assisted three-dimensional sonourethrography in clinical practice.

PURPOSE: This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture. METHODS: The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman's correlation analysis was executed to assess the findings. RESULTS: The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 min. The mean intraoperative length of urethral stricture was determined to be 14.4 ± 8.4 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.1 ± 7.5 mm and 13.4 ± 7.2 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman's correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.870 vs. 0.820). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives. CONCLUSIONS: The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application.

The effect of the 5-HT2A/2C receptor agonist DOI on micturition in rats with chronic spinal cord injury.

PURPOSE: We examined the effects of the 5-HT2A/2C receptor agonist DOI on micturition in chronic spinal cord injured rats. MATERIALS AND METHODS: Female Sprague-Dawley® rats were used. Spinal cord injury was produced by transection at the T10 level. A cystometric study was performed 8 to 12 weeks after transection. Cystometrograms were done using urethane anesthesia in all rats. The selective 5-HT2A antagonist ketanserin was administered after each DOI dose-response curve. All drugs were administered intravenously. RESULTS: Compared to controls, spinal cord injured rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. In spinal cord injured rats DOI (0.01 to 0.3 mg/kg) induced significant dose dependent increases in micturition volume and decreases in residual volume, resulting in increased voiding efficiency. Cystometrogram measurements showed a dose dependent increase in high frequency oscillation activity, evident as an increased number of small oscillation per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI induced changes. CONCLUSIONS: High frequency oscillation seems to reflect external urethral sphincter burst activity during voiding. Bladder voiding efficiency and high frequency oscillation activity were decreased in spinal cord injured rats. High frequency oscillation activity can be enhanced by 5-HT2A receptor agonism, improving voiding efficiency. To our knowledge it remains to be studied whether these results may have implications for the future treatment of voiding dysfunction in patients with spinal cord injury.

A rationale for procedure selection to repair female urethral stricture associated with urethrovaginal fistulas.

PURPOSE: We investigated a rationale for procedure selection to repair female urethral stricture associated with urethrovaginal fistula. We compared the outcomes of the 5 techniques used. MATERIALS AND METHODS: Between January 1999 and October 2011, 44 female patients with urethral stricture associated with urethrovaginal fistula were treated using a total of 5 techniques. The surgical techniques were labial pedicle flap urethroplasty in 24 patients, vulvar flap urethroplasty in 3, anterior vaginal flap urethroplasty in 11, end-to-end anastomosis in 4 and bladder flap urethroplasty in 2. Supplementary procedures were performed in some patients during urethroplasty, including bladder neck reshaping for incontinence in 5, intestinal-vaginal fistula repair in 3, colpoplasty for island vulvar skin flaps in 3, middle vaginal stricture vaginoplasty in 2 and enlargement of the vaginal introitus in 1. RESULTS: Average postoperative followup was 42.3 months (range 6 to 140). Urethrovaginal fistula recurred in 2 patients because of infection, urethral stricture developed in 1 and stress incontinence appeared in 1. The other patients voided normally with an average maximum urine flow greater than 15 ml per second (range 16.7 to 46). The overall anatomical success rate was 93.18% (41 of 44 cases) and the functional success rate was 90.91% (40 of 44). CONCLUSIONS: Surgical procedures for treating female urethral strictures with urethrovaginal fistulas should be based on fistula location, stricture length and vaginal anatomy. A transvaginal approach might be optimal if the vagina is wide and easily dilated. Pedicle labial flap urethroplasty was a reliable technique for complex strictures.

Association of GSTT1 gene polymorphisms with the risk of prostate cancer: an updating meta-analysis.

It has been demonstrated that the glutathione S-transferase (GST) superfamily helps remove carcinogens from the body and thus might be associated with prostate cancer risk. In recent years, GSTT1 polymorphism has been extensively studied as a potential prostate cancer risk factor; however, the results are inconsistent. To investigate the association between GSTT1 and prostate cancer, we conducted a meta-analysis of 33 studies with 6,697 prostate patients and 7,643 controls. For GSTM1 null versus present genotype, the random effects odds ratio was 0.98 (95 % confidence interval (CI) 0.83-1.16) based on a wide population. Subgroup analyses in the different ethnic groups and different controls were performed. The OR was 1.01 (95 % CI 0.86-1.19) in Caucasians, 1.01 (95 % CI 0.70-1.47) in Asians, and 0.77 (95 % CI 0.42-1.42) in Africans. The OR was 0.98 (95 % CI 0.82-1.16) in non-benign prostate hyperplasia (BPH) controls and 1.09 (95 % CI 0.66-1.79) in BPH controls. In conclusion, our present meta-analysis demonstrates that there is no association between GSTT1 polymorphism and prostate cancer, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of GSTT1 and prostate cancer but also on gene-environment interaction and distinctions of different GSTs.

Recurrence and complications after transperineal bulboprostatic anastomosis for posterior urethral strictures resulting from pelvic fracture: a retrospective study from a urethral referral centre.

OBJECTIVE: To describe the complications of transperineal end-to-end anastomotic urethroplasty in patients with posterior urethral strictures resulting from pelvic fracture. MATERIALS AND METHODS: A total of 573 patients, who underwent bulboprostatic anastomosis for posterior urethral strictures, were enrolled in this study. Distraction defects were measured using retrograde urethrography combined with voiding cysto-urethrography. All patients underwent perineal excision and primary anastomotic urethroplasty. The urethroplasty was considered successful if the patient was free of stricture-related obstruction and did not require any further intervention. The degree of stress incontinence was assessed daily by pad testing. The prevalence of pre- and postoperative sexual disorders was investigated using the International Index of Erectile Function-5 questionnaire. RESULTS: Of 573 bulboprostatic anastomosis procedures performed, 504 (88%) were successful and 69 (12%) were not successful. The mean (sd) maximum urinary flow rate, assessed by uroflowmetry 4 weeks after surgery, was 20.52 (5.1) mL/s. Intraoperative rectal injury was repaired primarily in 28 cases. Recurrence of urethral strictures was observed in 10 (1.7%) patients during the first 6 months after surgery, and in 45 patients from 6 months to 1 year. All of these patients underwent re-operation. Twenty-four (4.2%) patients had mild urge incontinence and 28 (4.9%) had mild stress incontinence. Erectile dysfunction (ED) was present in two (<0.1%) patients before trauma and in 487 (85%) patients after trauma. There was no statistical difference between the incidences of preoperative and postoperative ED (85 vs 86%, P > 0.05). Nine (1%) patients were found to have false passage between the posterior urethra and bladder neck. CONCLUSION: The majority of complications associated with transperineal bulboprostatic anastomosis can be avoided as long as meticulous preoperative evaluation to define the anatomy and careful intra-operative manipulation are ensured.

The relationship between erectile dysfunction and open urethroplasty: a systematic review and meta-analysis.

INTRODUCTION: Various urethroplasty techniques have been used to treat urethral stricture. Whether the patient erectile function is affected by this open surgery is still controversial. AIM: The aim of this study is to determine the relationship between erectile function and open urethroplasty. METHODS: A systematic review of the literature was performed using Medline, Embase, the Web of Science, and the Cochrane Library databases through October 2012 to identify articles published in any language that examined the effect of open urethroplasty on the risk of erectile dysfunction (ED). This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology. MAIN OUTCOME MEASURES: The incidence of ED after urethroplasty. RESULTS: This meta-analysis consisted of 23 cohort studies, which included 1,729 cases. No significant difference was noticed in patients with anterior urethral stricture before or after intervention (odds ratio [OR] = 0.86; 95% confidence interval [CI]: 0.52-1.40; P = 0.53). While statistical difference in the incidence of ED was revealed in patients before and after intervention for a posterior urethral (OR = 2.51; 95% CI: 1.82-3.45; P < 0.001), further comparisons demonstrated that most anterior urethroplasties did not have an obvious effect on patient erectile function. However, it seems that the incidence of ED was higher in the bulbar anastomosis group than in the oral graft urethroplasty group (OR = 0.32 95% CI: 0.11-0.93; P = 0.04). For the posterior urethroplasty, previous operative history did not show a strong relationship with ED. No statistically significant difference in the risk of ED was demonstrated comparing the posterior urethral reconstructive techniques included in this analysis. CONCLUSION: The adverse effect of urethroplasty itself on erectile function is limited, as more patients recover erectile function after urethral reconstruction. For anterior urethroplasty, bulbar anastomosis might cause a slightly higher incidence of ED than other operations. For posterior urethroplasty, trauma might be the main cause of ED.

Evaluation of stretched electrospun silk fibroin matrices seeded with urothelial cells for urethra reconstruction.

BACKGROUND: We investigated the feasibility of urethral reconstruction using stretched electrospun silk fibroin matrices. MATERIALS AND METHODS: A novel electrospun silk fibroin matrix was prepared. The structure of the material was assessed by scanning electron microscopy and a porosity test. Canine urothelial cells were isolated, expanded, and seeded onto the material for 1 wk to obtain a tissue-engineered graft. The tissue-engineered graft was assessed using hematoxylin and eosin staining and scanning electron microscopy. A dorsal urethral mucosal defect was created in nine female beagle dogs. In the experimental group, tissue-engineered mucosa was used to repair urethra mucosa defects in six dogs. No substitute was used in the three dogs of the control group. Retrograde urethrography was performed at 1, 2, and 6 mo after grafting. The urethral grafts were analyzed grossly and histologically. RESULTS: Scanning electron microscope and a porosity test revealed that the material had a three-dimensional porous structure. Urothelial cells grew on the material and showed good biocompatibility with the stretched silk fibroin matrices. Canines implanted with tissue-engineered mucosa voided without difficulty. Retrograde urethrography revealed no signs of stricture. Histologic staining showed gradual epithelial cell development and stratified epithelial layers at 1, 2, and 6 mo. The canines in the control group showed difficulty in voiding. Retrograde urethrography showed urethra stricture. Histologic staining showed that no or only one layer of epithelial cells developed. A severe inflammatory reaction was also observed in the control group. CONCLUSIONS: Stretched electrospun silk fibroin matrices have good biocompatibility with urothelial cells, which could prove to be a potential material for use in urethra reconstruction.