Diagnosis and treatment of anterior urethral strictures in China: an internet-based survey.

BACKGROUND: To investigate the current diagnostic and therapeutic approaches to anterior urethral strictures of Chinese urologists and to compare with developed countries and the American Urologic Association guidelines. METHODS: Anonymous questionnaires were distributed to members of Official Wechat Account of urology from March 19, 2020 to April 10, 2020. Descriptive and multiple correspondence analysis were used to analyze the data. RESULTS: A total of 1276 online questionnaires were received. The response rate was 21.7% (1276/5878). The most common diagnostic methods for anterior urethral stricture were urethrography (90.7%) and urethrocystoscopy (85.4%), while urethral dilation (92.3%) and internal urethrotomy (60.1%) were the main therapeutic procedures. End-to-end urethroplasty (45.2%) was the most common open surgery, followed by skin flap urethroplasty (14.9%) and free graft urethroplasty (12.4%). 76.2% of urologists used urethroplasty only after the failure of minimally invasive surgery (reconstructive ladder treatment strategy). Furthermore, middle-aged or elderly urologists who had attended trainings, had senior practice roles, and who utilized a reconstructive ladder treatment approach were most likely to perform urethroplasties. CONCLUSIONS: Anterior urethral stricture treatment in China is still dominated by minimally invasive surgery, with most urologists using the reconstructive ladder treatment strategy. In general, the overall diagnostic and therapeutic strategies were similar between China and developed countries, with some deviations from the American Urologic Association guidelines.

[Treatment of erectile dysfunction caused by cavernous nerve injury: An update].

With the development of prostate surgery and increasing number of patients with pelvic fracture urethral injury, ED caused by cavernous nerve injury (CNI) has attracted more and more medical attention. CNI induces the apoptosis of penile smooth muscle cells and endothelial cells, decreases the density of NOS-positive nerves, and results in the fibrosis of the cavernous smooth muscle. The strategies of nerve regeneration after CNI has been one of the hotspots in the studies of ED. This review focuses on the current treatment strategies to promote the cavernous nerve regeneration and status quo of basic and clinical researches on the treatment of CNI-induced ED. The treatment strategies discussed in this review involve neurotrophic factors, RhoA/ROCK inhibitors, immunophilic ligands, erythropoietin, stem cell therapy, gene therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, which are all new and suitable for clinical transformation.

Construction of a three-dimensional urothelium on-chip with barrier function based on urinary flow microenvironment.

The urothelium covers the inner surface of the urinary tract, forming a urinary tract barrier. Impairment of the integrity and dysfunction of the urinary tract barrier is associated with the occurrence and development of various diseases. The development of a three-dimensional model of the urothelium is critical for pathophysiological studies of this site, especially under physiological fluid shear stress stimulated by the urinary flow. In this study, a urothelium on-chip is fabricated with micromilling and replica molding techniques, which contains a microfluidic chip for cell culture and a pump-based fluid perfusion system. The mechanical properties of the human urinary tract are simulated by adjusting the concentration and degree of amino substitution of the gelatin methacrylate hydrogel. The matrix stiffness is similar to the natural urinary tract. Pulsatile flow and periodic flow are provided to simulate the fluid environment of the upper and lower urinary tracts, respectively. The results show that the physiological fluid shear stress could promote the differentiation and maturation of urothelial cells. The model could simulate the three-dimensional structure of urothelium and urinary flow microenvironment, showing morphological structure close to the natural urothelium, specific differentiation and maturation markers (uroplakin 2, cytokeratin 20), and urothelial barrier function.

Application of microfluidic chips in the simulation of the urinary system microenvironment.

The urinary system, comprising the kidneys, ureters, bladder, and urethra, has a unique mechanical and fluid microenvironment, which is essential to the urinary system growth and development. Microfluidic models, based on micromachining and tissue engineering technology, can integrate pathophysiological characteristics, maintain cell-cell and cell-extracellular matrix interactions, and accurately simulate the vital characteristics of human tissue microenvironments. Additionally, these models facilitate improved visualization and integration and meet the requirements of the laminar flow environment of the urinary system. However, several challenges continue to impede the development of a tissue microenvironment with controllable conditions closely resemble physiological conditions. In this review, we describe the biochemical and physical microenvironment of the urinary system and explore the feasibility of microfluidic technology in simulating the urinary microenvironment and pathophysiological characteristics in vitro. Moreover, we summarize the current research progress on adapting microfluidic chips for constructing the urinary microenvironment. Finally, we discuss the current challenges and suggest directions for future development and application of microfluidic technology in constructing the urinary microenvironment in vitro.

The treatment practices for anterior urethral strictures in China: A case-based survey.

Objective: To investigate the treatment concept of Chinese urologists for anterior urethral strictures based on actual cases. Methods: A self-designed case-based questionnaire was distributed to the members of Official WeChat account of Learning Union from March 19, 2020, to April 10, 2020. Questionnaires requested respondents' demographic information and responses to five cases of anterior urethral stricture: short obliterative bulbar urethral stricture caused by straddle injury (Case 1), idiopathic bulbar urethral stricture after failure of multiple endoscopic therapy (Case 2), iatrogenic long penile urethral stricture (Case 3), lichen sclerosis-related urethral stricture (Case 4), and anterior urethral stricture in indwelling catheter after multiple failure of endoscopic surgery (Case 5). Data was described by frequency and percentage. Results: A total of 1,267 valid anonymous questionnaires were received. Urethroplasty was recommended more frequently than endoscopic surgery (Case 1: 47.8% vs. 32.8%,Case 2: 42.5% vs. 33.8%, Case 3: 36.1% vs. 26.7%). Referrals patients to other urologists engaged in urethral repair and reconstruction account for a high portion of the treatment (Case 1:18.4%, Case 2:23.1%, Case 3:36.5%, Case 4:27.7%,Case 5:9.3%). Excision and primary anastomosis urethroplasty (EPA) was preferred for treatment of Case 1 (42.5%). For Case 2, the most popular choice was EPA (30.6%). Although the patient has a history of failure in endoscopic surgery, 33.8% of urologists continue to choose endoscopic surgery. For Case 3, 20.0% of urologists would perform oral mucosal urethroplasty. Surprisingly, 5.9% chose EPA. For Case 4, 37.3% of urologists selected meatotomy, 30.4% suggested that glans and urethral biopsies should be performed. 21.0% chose to use steroid ointment after surgery. For Case 5, 26.3% of the respondents believed that urethrography should be performed after removing catheter more than one week, if the urine is obstructed during the period, performing cystostomy firstly. Conclusions: In China, the concept of urethroplasty is more widely accepted than endoscopic surgery for the treatment of anterior urethral strictures. The concept of referral has been widely formed among Chinese urologists. Better understanding of the comprehensive treatment of lichen sclerosis related anterior urethral stricture and the principle of urethral rest should be strengthened.

Postoperative Infection of Male Posterior Urethral Stenosis with Pelvic Fracture: A Retrospective Study from a Chinese Tertiary Teferral Center.

OBJECTIVES: To investigate the risk factors for postoperative infection, including systemic inflammatory response syndrome, sepsis and surgical site infection, after posterior urethral anastomosis for the treatment of male posterior urethral stenosis with pelvic fractures. METHODS: We retrospectively analyzed data from patients who underwent transperineal end-to-end anastomotic urethroplasty between January 2016 and December 2018. Descriptive statistics were used to analyze patient characteristics and perioperative features. Univariate analysis was performed to identify prognostic factors associated with postoperative infection. Multivariate analysis was used to identify independent risk factors for postoperative infection. RESULTS: Among 261 patients included in the analysis, 16.48% had SIRS, 3.83% had sepsis, and 8.05% had SSI. The primary results suggested that penile septum separation, inferior pubic resection, operating duration, preoperative urine culture result, preoperative waiting time, urethral stenosis length, and draining method were significant predictors of postoperative infections. Multivariate analysis revealed that more complex surgical procedures, operating duration and positive urine culture results were independent risk factors for SIRS and preoperative positive urine culture result was an independent risk factor for sepsis and SSI. CONCLUSIONS: Positive preoperative urine culture was the main risk factor for postoperative infections. More complex surgical procedures, such as penile septum separation and inferior pubic resection, and longer operating duration were more likely to be associated with postoperative SIRS.

Cryopreserved skin epithelial cell sheet combined with acellular amniotic membrane as an off-the-shelf scaffold for urethral regeneration.

BACKGROUND: Autologous tissue transplantation for urethral repair is often limited and causes donor site complications. Here, a cryopreserved rabbit skin epithelial cell sheet (SEC) combined with an acellular amniotic membrane (AM) was used to repair rabbit urethral defects. METHODS: Abdominal skin was collected from 4-week-old New Zealand rabbits, and primary epithelial cells were extracted and cultured to form a cell sheet. Fresh SEC-AMs were constructed and cryopreserved. A cryopreservation system including optimized medium, two-pump perfusion, a programmed freezer and liquid nitrogen storage was established. Cell viability, mechanical strength, electron microscopy, and histological staining were performed in vitro after 1 month. Next, the sheets were transplanted subcutaneously for 2 weeks, and the graft was used to repair the rabbit urethral defect. Urinary function was measured and samples were collected for histological staining after 1 month. RESULTS: We confirmed that cryopreservation damage of SECs was reduced by composition with acellular AMs in terms of high cell activity. The SEC mechanical strength was also enhanced by AMs, which was convenient for the operation. In in vivo experiments, we transplanted sheets into the groin area for two weeks and found that cryopreservation reduced inflammatory cell infiltration and significantly improved vascular density. In the urethral repair experiment, the near-normal passive urine flow rate, smooth mucosa of the gross specimen, intact epithelialization and abundant neovascularization were confirmed in the cryopreserved-SEC-AM group compared with the other groups. CONCLUSIONS: Cryopreserved SEC-AMs demonstrated similar outcomes of rabbit urethral defect repair as fresh SEC-AMs, showing good clinical application prospects.

Sustained release of stromal cell-derived factor-1 alpha from silk fibroin microfiber promotes urethral reconstruction in rabbits.

We developed a stromal cell-derived factor-1 alpha (SDF-1α)-aligned silk fibroin (SF)/three-dimensional porous bladder acellular matrix graft (3D-BAMG) composite scaffold for long-section ventral urethral regeneration and repair in vivo. SDF-1α-aligned SF microfiber/3D-BAMG, aligned SF microfiber/3D-BAMG, and nonaligned SF microfiber/3D-BAMG scaffolds were prepared using electrostatic spinning and wet processing. Adipose-derived stem cell (ADSC) and bone marrow stromal cell (BMSC) migration was assessed in the SDF-1α-loaded scaffolds. Sustained SDF-1α release in vitro and vivo was analyzed using enzyme-linked immunosorbent assay (ELISA) and western blotting, respectively. The scaffolds were used to repair a 1.5 × 1 cm2 ventral urethral defect in male rabbits in vivo. General observation and retrograde urinary tract contrast assessment were used to examine urethral lumen patency and continuity at 1 and 3 months post-surgery. Postoperative rehabilitation was evaluated using histological detection. The composite scaffolds sustained SDF-1α release for over 16 days in vitro. SDF-1α-aligned SF nanofiber promoted regeneration of urethral mucosa, submucosal smooth muscles, and microvasculature, increased cellular proliferation, and reduced collagen deposition. SDF-1α expression was increased in reconstructed urethra at 3 months post-surgery in SDF-1α-aligned SF group. SDF-1α-aligned SF microfiber/3D-BAMG scaffolds may be used to repair and reconstruct long urethral defects because they accelerate urethral regeneration.

The value of magnetic resonance imaging geometric parameters in pre-assessing the surgical approaches of pelvic fracture urethral injury.

BACKGROUND: To investigate the correlation between the magnetic resonance urethrography and the surgical approach and complexity for the patients with pelvic fracture urethral injury (PFUI) by combining the geometry with magnetic resonance imaging (MRI). METHODS: Forty-three male patients with PFUI (part of the patients complicated with rectal injury) from January 2016 to December 2018 were analyzed in this retrospective research. All the patients underwent a delayed anastomotic urethroplasty and were divided into 2 groups according to the approaches (simple perineal approach or inferior pubectomy). For magnetic resonance urethrography, we measured and calculated the geometric parameters such as the gap distance between two urethral ends, the pubourethral vertical distance (PUVD), and the rectourethral median distance (RUMD). RESULTS: Of the 43 patients, 16 underwent inferior pubectomy and 27 underwent simple perineal approach. The numbers of patients with and without rectal injury history were 17 and 26, respectively. The operation time and intraoperative blood loss was significantly higher in the inferior pubectomy group. Multivariate logistic analysis revealed that gap distance and PUVD were independent factors of the surgical approaches. The accuracies were 83.7% and 67.4% respectively in the ROC curve analysis. In addition, the RUMD was significantly shorter in the patients with rectal injury history (1.4, 1.8 cm). CONCLUSIONS: Longer gap distance and shorter PUVD were the two independent factors of the inferior pubectomy approach. Furthermore, among the patients with rectal injury history, the tissue posterior to the urethra was often weaker and should be carefully handled during the surgery. TRIAL REGISTRATION: This research has been registered on the Chinese Clinical Trial Registry. The registration number is ChiCTR2000030573.

Adding a vacuum erection device to regular use of Tadalafil improves penile rehabilitation after posterior urethroplasty.

This study aimed to evaluate whether adding a vacuum erection device (VED) to regular use of Tadalafil could achieve better penile rehabilitation following posterior urethroplasty for pelvic fracture-related urethral injury (PFUI). Altogether, 78 PFUI patients with erectile dysfunction (ED) after primary posterior urethroplasty were enrolled and divided into two treatment groups: VED combined with Tadalafil (Group 1, n = 36) and Tadalafil only (Group 2, n = 42). Changes in penile length, testosterone level, International Index of Erectile Function-5 (IIEF-5) questionnaire, Quality of Erection Questionnaire (QEQ), and nocturnal penile tumescence (NPT) testing were used to assess erectile function before and after 6 months of ED treatment. Results showed that the addition of VED to regular use of Tadalafil preserved more penile length statistically (0.4 ± 0.9 vs -0.8 ± 0.7 cm, P < 0.01). IIEF-5 score and QEQ score in Group 1 were higher than Group 2 (both P < 0.05). After treatment, 21/36 (58.3%) Group 1 patients and 19/42 (45.2%) Group 2 patients could complete vaginal penetration. Group 1 patients also had markedly improved testosterone levels (P = 0.01). Unexpectedly, there was no significant difference in NPT testing between two therapies. For PFUI patients with ED after posterior urethroplasty, the addition of VED to regular use of Tadalafil could significantly improve their conditions - improving erection and increasing penile length - thus increasing patient satisfaction and confidence in penile rehabilitation.