High frequency of concomitant squamous metaplasia in bulbar urethral stricture and its association with reconstructive delay and urethral rest.

PURPOSE: To determine the prevalence of concomitant squamous metaplasia (SM), the initial histological change from normal urethra to urethral stricture, in bulbar urethral strictures and to investigate the associated clinical factors. METHODS: A retrospective review was conducted on 165 male patients with bulbar urethral strictures who underwent excision and primary anastomosis (EPA) between 2010 and 2020, for whom complete clinical data and excised urethral specimens were available. An experienced pathologist histologically evaluated concomitant SM in paraffin sections of the proximal end of the excised urethra blinded to the clinical data. Disease duration was calculated as the period from the initial diagnosis of urethral stricture to the date of EPA. The association between concomitant SM and clinical background was investigated. RESULTS: SM was identified in 86 (52.1%) patients. The median disease duration in patients with SM (38 months) was significantly longer than that in patients without SM (9 months, p < 0.0001). In multivariate analysis, the longer disease duration, non-traumatic stricture etiology, and failure to maintain urethral rest with urinary diversion via a suprapubic tube for more than 90 days were independent factors predicting concomitant SM. No significant difference was observed in success rates of EPA between patients with SM (93.2%) and those without SM (97.5%, p = 0.18). CONCLUSIONS: Reconstructive urologists need to be aware that concomitant SM is frequent in patients with bulbar urethral stricture, especially in those with long disease duration and those who were voiding volitionally during the period of urethral rest.

Urosymphyseal fistula development following treatment for radiation-induced urethral stenosis in three patients with prostate cancer.

Introduction: Urosymphyseal fistula is a rare and devastating complication that develops after radiation therapy for prostate cancer and is often triggered by the treatment of radiation-induced urethral stenosis. Here, we report our experience with urosymphyseal fistulas in three patients with prostate cancer. Case presentation: Three patients with prostate cancer developed urethral stenosis after radiotherapy. The management of urethral stenosis was suprapubic tube placement in case 1, direct vision internal urethrotomy in case 2, and excision with primary anastomosis in case 3. All patients presented with severe suprapubic or thigh pain or both. Urosymphyseal fistulas were detected on magnetic resonance imaging. Conservative treatment was unsuccessful, and all patients required debridement of the necrotic pubic symphysis and simple cystectomy. In cases 1 and 2, ileal conduit urinary diversion was performed. Conclusion: Urologists need to be aware that urosymphyseal fistulas can occur in irradiated patients with prostate cancer, especially after urethral stenosis treatment.

The Japanese Urological Association's clinical practice guidelines for urotrauma 2023.

The Japanese Urological Association's guidelines for the treatment of renal trauma were published in 2016. In conjunction with its revision, herein, we present the new guidelines for overall urotrauma. Its purpose is to provide standard diagnostic and treatment recommendations for urotrauma, including iatrogenic trauma, to preserve organ function and minimize complications and fatality. The guidelines committee comprised urologists with experience in urotrauma care, selected by the Trauma and Emergency Medicine Subcommittee of the Specialty Area Committee of the Japanese Urological Association, and specialists recommended by the Japanese Association for the Surgery of Trauma and the Japanese Society of Interventional Radiology. The guidelines committee established the domains of renal and ureteral, bladder, urethral, and genital trauma, and determined the lead person for each domain. A total of 30 clinical questions (CQs) were established for all domains; 15 for renal and ureteral trauma and five each for the other domains. An extensive literature search was conducted for studies published between January 1, 1983 and July 16, 2020, based on the preset keywords for each CQ. Since only few randomized controlled trials or meta-analyses were found on urotrauma clinical practice, conducting a systematic review and summarizing the evidence proved challenging; hence, the grade of recommendation was determined according to the 2007 "Minds Handbook for Clinical Practice Guidelines" based on a consensus reached by the guidelines committee. We hope that these guidelines will be useful for clinicians in their daily practice, especially those involved in urotrauma care.

Myofibroblast-dominant proliferation associated with severe fibrosis in bulbar urethral strictures.

OBJECTIVES: Myofibroblast-dominant proliferation (relative to fibroblast proliferation) is the key process in urethral fibrosis, but its association with clinical features is not understood. We conducted a histological analysis of urethral strictures and examined the association between myofibroblast proliferation and stricture characteristics. METHODS: Formalin-fixed, paraffin-embedded urethral sections sliced axially from 175 male patients with bulbar urethral strictures were retrospectively analyzed. All patients underwent excision and primary anastomosis between September 2008 and January 2021 by a surgeon (AH). Masson's trichrome stain was used to estimate the area of fibrosis. Corresponding unstained slides with the largest area of fibrosis were selected and double-immunostained with anti-smooth muscle actin (SMA) and anti-TE-7 mouse monoclonal antibodies for the assessment of myofibroblasts and fibroblasts, respectively. The ratio of the number of SMA-positive cells to the number of TE-7-positive cells (SMA/TE-7 ratio) was calculated. RESULTS: The area of fibrosis in strictures due to perineal trauma (n = 85, median 108.9 mm2 ) was significantly larger than that in non-traumatic strictures (n = 90, median 42.9 mm2 , p < 0.0001). The area of fibrosis positively correlated with SMA expression (r = 0.35, p < 0.0001) and the SMA/TE-7 ratio (r = 0.36, p < 0.0001), but not with TE-7 expression (r = -0.01, p = 0.75). In a multivariate linear regression model, traumatic etiology (standard coefficient 0.37, t value 3.9, p < 0.0001) and increased SMA expression (standard coefficient 0.17, t value 2.1, p = 0.03) were the predictors of wide fibrosis area. CONCLUSIONS: Myofibroblast-dominant proliferation may contribute to the pathogenesis of severe urethral fibrosis.

Transperineal bulbovesical anastomosis for extensive posterior urethral stenoses after treatment of prostatic disease.

OBJECTIVES: We report our surgical experience of transperineal bulbovesical anastomosis (BVA) for extensive posterior urethral stenosis (PUS). METHODS: Six male patients who had extensive PUS extending from the bulbomembranous urethra to the bladder neck due to prostatic disease treatment and underwent transperineal BVA between 2014 and 2020 were retrospectively reviewed. BVA was performed according to the elaborate perineal approach for pelvic fracture urethral repair with minor modifications. After confirming the absence of recurrent stenosis 6 months postoperatively, the patients were offered artificial urinary sphincter (AUS) placement for subsequent urinary incontinence (UI). RESULTS: Median patient age was 68, and the etiology of PUS was radical prostatectomy for prostate cancer in four patients, brachytherapy for prostate cancer in one, and transurethral resection of the prostate for benign prostatic hyperplasia in one. All patients had been previously treated with multiple transurethral procedures such as urethrotomy and dilation. Median operative time and blood loss were 211 min and 154 ml, respectively. Five cases (83.3%) had no recurrent stenosis with a median follow-up of 45 months, but a single direct vision internal urethrotomy was performed in one (16.7%) due to restenosis. Four (66.7%) patients underwent AUS placement via transcorporal approach for subsequent UI, but two had it removed due to urethral erosion. CONCLUSION: Transperineal BVA could effectively manage extensive PUS after prostatic disease treatment. Staged AUS placement could be a viable option for subsequent UI, but the risk of urethral erosion seemed high.

Efficacy of urethral reconstruction for urethral stricture associated with hypospadias surgery in adults.

OBJECTIVES: We report our experience with urethral reconstruction for hypospadias surgery-related urethral stricture in terms of surgical and patient-reported outcomes. METHODS: Twenty-nine adult males who underwent urethral reconstruction for hypospadias surgery-related urethral stricture between August 2008 and January 2022 were retrospectively reviewed. Uroflowmetry and patient-reported outcomes were evaluated at 3, 6, and 12 months, and annually thereafter. Surgical success was defined as the absence of additional procedures. Patients were asked to rate their satisfaction with urethral reconstruction as "very satisfied", "satisfied", "unsatisfied", or "very unsatisfied". RESULTS: The median patient age at referral was 43 years. The median number of previously performed hypospadias surgeries was three, and 18 patients (62.8%) had been treated with repeated transurethral procedures. The median stricture length was 54 mm (interquartile range 36-81). Performed urethral reconstruction included staged urethroplasty in 22 (75.9%), one-stage onlay augmentation in 3 (10.2%), and perineal urethrostomy in 4 (13.8%) cases. Urethral reconstruction was successful in 26 patients (89.7%) over a median postoperative period of 31 months. Patient-reported outcomes were assessed in 25 (86.2%) patients. The mean maximum flow rate, international prostate symptom score total score, international prostate symptom score quality of life score, and EuroQol-5 dimensions index significantly improved postoperatively. Twenty-three patients (92%) were "very satisfied" or "satisfied" with the outcome of their urethral reconstruction. CONCLUSIONS: Urethral reconstruction is a highly successful and patient-satisfying treatment for hypospadias surgery-related urethral stricture in adult patients. Perineal urethrostomy is a reasonable alternative for elderly patients and for patients with complicated hypospadias surgery-related urethral strictures.

Urethral reconstruction for iatrogenic urethral stricture after transurethral prostate surgery: An analysis of surgical and patient-reported outcomes.

OBJECTIVES: We investigated the efficacy of urethral reconstruction in male patients with iatrogenic urethral stricture after transurethral prostate surgery. METHODS: We retrospectively reviewed the cases of 82 patients who underwent urethral reconstruction for iatrogenic urethral stricture caused by transurethral prostate surgery between August 2011 and July 2021. Patients were followed up postoperatively with uroflowmetry, postvoid residual urine measurement, and questionnaires using Peeling's picture score, International Prostate Symptom Score, International Consultation on Incontinence Questionnaire Short Form, Sexual Health Inventory for Men, EuroQol-5 dimensions, and EuroQol-5 dimensions visual analog scores. Successful urethral reconstruction was defined as the absence of a postoperative decrease in urinary force and any additional treatment. RESULTS: The median patient age was 72 years, and the stricture site was the urethral meatus in eight (9.8%) patients, penoscrotal junction in 42 (51.2%), and proximal bulbar urethra in 26 (31.7%). Six patients (7.3%) had synchronous urethral strictures. Urethral reconstruction was successful in 78 patients (95.1%), with a median follow-up of 43 months. The mean maximum flow rate (P < 0.0001), postvoid residual urine (P = 0.004), Peeling's picture score (P < 0.0001), the score for each question and total International Prostate Symptom Score and International Prostate Symptom Score-quality of life scores (P < 0.0001 for all comparisons), and EuroQol-5 dimensions and EuroQol-5 dimensions visual analog scores (P < 0.0001 for both) significantly improved postoperatively. However, the Sexual Health Inventory for Men and International Consultation on Incontinence Questionnaire Short Form scores remained unchanged (P = 0.09 and 0.70, respectively). CONCLUSIONS: Urethral reconstruction was effective for urethral stricture due to transurethral prostate surgery in both subjective and objective aspects.

Surgical and Patient-Reported Outcomes of Delayed Anastomotic Urethroplasty for Male Pelvic Fracture Urethral Injury at a Japanese Referral Center.

We aimed to assess the surgical and patient-reported outcomes of delayed anastomotic urethroplasty (DAU) for pelvic fracture urethral injury (PFUI). We included 211 male patients who underwent DAU for PFUI. DAU success was considered when the urethral lumen was sufficiently large for the passage of a flexible cystoscope, without additional treatment required. The patients completed the lower urinary tract symptoms (LUTS)-related quality of life (QOL) questionnaire (scores: 0, not at all; 1, a little; 2, somewhat; 3, a lot), EuroQol-5 dimensions (EQ-5D), and EQ-5D visual analog scale (EQ-VAS). Postoperative overall satisfaction was evaluated using the following responses: "very satisfied," "satisfied," "unsatisfied," or "very unsatisfied." DAU was successful in 95.3% cases, with a median postoperative follow-up duration of 48 months. Multivariate logistic regression analysis revealed that "greater blood loss" was an independent predictor of failed urethroplasty. Questionnaire responses were obtained from 80.1% patients. The mean LUTS-related QOL, EQ-5D score and EQ-VAS improved significantly from 2.8, 0.63 and 54.4 at baseline to 0.9, 0.81 and 76.6 postoperatively (p < 0.0001 for all parameters). Moreover, 35.5% and 59.2% of the patients responded being "satisfied" and "very satisfied," respectively, with their DAU outcomes. DAU not only had a high surgical success rate, but also a significant beneficial effect on both LUTS-related QOL and overall health-related QOL.

Role of magnetic resonance imaging in the management of male pelvic fracture urethral injury.

The management of male pelvic fracture urethral injury remains a urological challenge. Pelvic fracture urethral injury can be associated with sequelae, such as urethral gap, erectile dysfunction and urinary incontinence. Delayed anastomotic urethroplasty, the gold standard treatment for urethral gaps caused by pelvic fracture urethral injuries, is technically demanding, and reconstructive urologists should preoperatively obtain as much detailed anatomical information as possible. A combination of antegrade and retrograde urethrography is the fundamental preoperative evaluation, but it cannot accurately assess the urethral gap length, the degree of lateral prostatic displacement, the anatomical relationship of the urethra with its surrounding structures (such as the rectum and dorsal venous complex) or periurethral problems (such as minor fistulae or cavitation). To make up for these limitations of urethrography, magnetic resonance imaging has emerged as a non-invasive, multiplanar and high-resolution modality for the evaluation of pelvic fracture urethral injury. Magnetic resonance imaging has excellent soft-tissue contrast, and can clearly show the urethra and periurethral tissues without the effects of radiation, thus enabling clinicians to anticipate the required ancillary techniques for delayed anastomotic urethroplasty and to predict functional outcomes, such as erectile function and urinary continence, after delayed anastomotic urethroplasty. This review discusses the role of magnetic resonance imaging in the evaluation of pelvic fracture urethral injury and its impact on patient management.

In Vitro Culture Expansion and Characterization of Buccal Mucosal Epithelial Cells for Tissue Engineering Applications in Urethral Stricture After Transportation Using a Thermoreversible Gelation Polymer.

Introduction: The transportation of tissues from hospitals to clinical laboratories for cell therapy is an essential component of regenerative medicine. Previously, we used laboratory-cultured mucosal cells from buccal epithelium expanded and encapsulated using a scaffold-hybrid approach to the urethral stricture (BEES-HAUS) procedure. In this study, to improve the outcomes, we compared the thermoreversible gelation polymer (TGP) transportation procedure with conventional culture methods, and reported its advantages. Methods: Human buccal mucosal tissues in Phase I of the study were transported in Euro-Collins solution (ECS) and the cells obtained were cultured in two-dimensional (2D) Dulbecco's modified Eagle's medium (DMEM), CnT-Prime epithelial 2D differentiation medium (CnT-PR), and a three-dimensional (3D)-TGP scaffold. In Phase II, tissues were transported in a TGP cocktail and the ECS. The cells were cultured in 2D-DMEM and 3D-TGP, quantified, and characterized by immunohistochemistry. Results: The cells in 3D-TGP culture maintained epithelial morphology in a better manner compared with 2D-DMEM, in which they developed fibroblast-like morphology. The TGP-transported cells grew rapidly. Immunohistochemical analysis results for AE1/AE3, EGFR, integrin-ß1, p63, and p75 were intensely positive in 3D-TGP. Conclusion: The TGP-based cocktail used in human buccal tissue transportation yielded cells with better morphology maintenance. The TGP scaffold provides an optimal in vitro environment wherein epithelial cells better maintain their native phenotype compared to those cultured through conventional methods. These results suggest using TGP for the transportation and culture of human buccal tissues for clinical applications. In addition, the use of a TGP-based cocktail for the transport of other tissues for regenerative medicine applications is worth further analysis.

Impact of urethroplasty on overactive bladder symptoms in patients with anterior urethral strictures.

OBJECTIVES: To investigate the incidence of overactive bladder in men with anterior urethral stricture and to evaluate the impact of urethroplasty on its improvement. METHODS: A total of 104 men with anterior urethral stricture who underwent urethroplasty between 2016 and 2020 completed a validated urethral stricture surgery patient-reported outcome measure comprising six lower urinary tract symptoms questions on voiding symptoms and overactive bladder symptom score before and 3, 6, and 12 months after urethroplasty. Patients with an urgency score of ≥2 for overactive bladder symptom score question 3, and a total overactive bladder symptom score of ≥3 were considered to have overactive bladder. An improvement in overactive bladder was defined as a decrease in the total overactive bladder symptom score by at least three points. RESULTS: Thirty-nine patients (37.5%) were considered to have overactive bladder, and improvement in overactive bladder after urethroplasty was found in 30 (76.9%). Maximum flow rate on uroflowmetry, postvoid residual urine volume, lower urinary tract symptoms total score, and total overactive bladder symptom score were all significantly improved after urethroplasty (P < 0.0001 for all variables). There was a positive correlation between changes in lower urinary tract symptoms total score and total overactive bladder symptom score (Spearman's correlation 0.48, P < 0.0001). Multivariate logistic regression analysis showed that greater change in lower urinary tract symptoms score was an independent predictor of improvement in overactive bladder (odds ratio 1.30, 95% confidence interval 1.06-1.59; P = 0.002). CONCLUSIONS: Overactive bladder is prevalent in patients with anterior urethral stricture, and can be effectively improved after urethroplasty. Improvement of voiding symptoms are key for improving overactive bladder symptoms.

Ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in rabbits.

OBJECTIVES: To evaluate the ability of photocurable gelatin to prevent stricture recurrence after urethral dilation in a rabbit urethral stricture model. METHODS: We created urethral strictures in the bulbar urethras of 10 male Japanese white rabbits using electrocoagulation. After 1 month, the rabbits were randomly divided into Group A (n = 5; urethral stricture dilation and the local application of photocurable gelatin using a ruthenium photoinitiator and irradiation with a light-emitting diode light [λ = 455 nm, 50 mW/cm2 ] for 1 min) and Group B (n = 5; dilation only). Urethral stricture status was evaluated 1-2 months later by retrograde urethrography and urethroscopy. The lumen ratio (urethral width at the stricture site to the normal urethral width on retrograde urethrography) was calculated. Urethral patency was considered to be improved when the urethral lumen could accommodate a 10-Fr urethroscope without resistance. Urethral specimens were harvested for histopathological examination. RESULTS: The mean lumen ratio did not differ significantly between Groups A and B before dilation (25.8% vs 23.4%; P = 0.40), but differed significantly after dilation (65.5% vs 27.3%, respectively; P = 0.03). Urethral patency improved in all rabbits in Group A (100%) versus one rabbit in Group B (20%; P = 0.02). The mean circumference of the regenerated urethral epithelium at the stricture site was larger in Group A than in Group B (14 mm vs 6.6 mm; P = 0.06). CONCLUSIONS: Photocurable gelatin can reduce urethral stricture recurrence after dilation in a rabbit model.

Membranous urethral length on magnetic resonance imaging as a novel predictor of urinary continence after delayed anastomotic urethroplasty for pelvic fracture urethral injury.

PURPOSE: We studied the impact of membranous urethral length (MUL) on magnetic resonance imaging (MRI) on post-urethroplasty continence in male patients with pelvic fracture urethral injury (PFUI). METHODS: Of 169 male patients with PFUI who underwent delayed anastomotic urethroplasty between 2008 and 2020, 85 who underwent preoperative MRI, had no recurrent stenosis on cystoscopy, and underwent a 1-h pad test 1 year after surgery were included. MUL was defined as the distance from the distal end of the disrupted proximal urethra to the apex of the prostate, as measured using T2-weighted MRI. Urinary incontinence (UI) was defined as a 1-h pad test weight > 2.0 g. RESULTS: None of the patients had UI before a pelvic fracture. Eighty-two patients (96.5%) had a measurable MUL, and the median length was 8.1 (interquartile range [IQR], 5.2-10.8) mm. The median weight of the 1-h pad test was 1.0 (IQR, 0.0-4.0) g, and 26 (30.6%) patients had UI. An open bladder neck (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.0-22.0; p = 0.04) and a short measurable membranous urethra (for every extra mm: OR, 1.2; 95% CI, 1.0-1.3; p = 0.04) were significant UI predictors on multivariate analysis. CONCLUSIONS: A long MUL is significantly positively associated with urinary continence in male patients with PFUI. This could be of potential value to reconstructive urologists when counseling patients regarding post-urethroplasty continence before urethroplasty.

Photocrosslinked gelatin hydrogel improves wound healing and skin flap survival by the sustained release of basic fibroblast growth factor.

Biomaterials traditionally used for wound healing can act as a temporary barrier to halt bleeding, prevent infection, and enhance regeneration. Hydrogels are among the best candidates for wound healing owing to their moisture retention and drug-releasing properties. Photo-polymerization using visible light irradiation is a promising method for hydrogel preparation since it can easily control spatiotemporal reaction kinetics and rapidly induce a single-step reaction under mild conditions. In this study, photocrosslinked gelatin hydrogels were imparted with properties namely fast wound adherence, strong wet tissue surface adhesion, greater biocompatibility, long-term bFGF release, and importantly, ease of use through the modification and combination of natural bio-macromolecules. The production of a gelatin hydrogel made of natural gelatin (which is superior to chemically modified gelatin), crosslinked by visible light, which is more desirable than UV light irradiation, will enable its prolonged application to uneven wound surfaces. This is due to its flexible shape, along with the administration of cell growth factors, such as bFGF, for tissue regeneration. Further, the sustained release of bFGF enhances wound healing and skin flap survival. The photocrosslinking gelatin hydrogel designed in this study is a potential candidate to enhance wound healing and better skin flap survival.

Deep lateral transurethral incision for vesicourethral anastomotic stenosis after radical prostatectomy.

OBJECTIVES: To investigate the outcomes of deep lateral incision for vesicourethral anastomotic stenosis after radical prostatectomy and its impact on postoperative urinary incontinence. METHODS: We retrospectively investigated 43 men who underwent deep lateral incision for non-obliterated vesicourethral anastomotic stenosis after radical prostatectomy between 2011 and 2020. The bladder neck was deeply incised through its circular fibers into the surrounding perivesical fat at 3 and 9 o'clock through electrocautery incision using needle-type electrodes. Successful deep lateral incision was defined as the absence of additional treatment, including self-dilatation. The postoperative urinary incontinence status was evaluated based on the number of pads used daily. RESULTS: Deep lateral incision was successful in 35 (81.4%) patients, with a median follow-up period of 43 months (interquartile range 15-80 months). There was no significant association of age (P = 0.66), body mass index (P = 0.49) and history of diabetes mellitus (P = 0.39), radiation therapy (P = 0.89) or previous vesicourethral anastomotic stenosis treatment (P = 0.71) with the incision outcomes; however, there were significantly more unsuccessful cases in those with preoperative urinary retention (P = 0.04) or indwelling urinary catheters for >5 days post-incision (P = 0.01). A second incision was carried out in eight patients and a third incision in two patients, resulting in 42 (97.7%) successful incisions. A total of 37 (88.1%) patients had urinary incontinence and used at least one pad daily; seven (16.7%) underwent artificial urinary sphincter implantation after the last incision. CONCLUSIONS: Deep lateral incision is highly effective for treating vesicourethral anastomotic stenosis after radical prostatectomy. Appropriate treatment is required for urinary incontinence, which occurs frequently after incision.

Evaluation of the efficacy of perineal urethrostomy for patients with anterior urethral stricture: insights from surgical and patient-reported outcomes.

PURPOSE: To examine the efficacy of perineal urethrostomy (PU) in patients with anterior urethral stricture. METHODS: Patients who underwent PU for anterior urethral stricture between 2013 and 2020 were retrospectively reviewed (n = 56). Surgical success was defined as no need for additional intervention. Uroflowmetry and measurement of residual urine volume (PVR) were examined postoperatively, and the patients were asked to fill out sexual health inventory for men (SHIM) and the validated Urethral Stricture Surgery Patient-reported Outcome Measure questionnaires before and after PU. The overall patient satisfaction was also assessed. RESULTS: PU was successful in 92.9% of patients (n = 52), with a median follow-up of 34 months. Two of four were salvaged by re-do PU, and one was salvaged by forming a composite stoma using a penile skin graft. Thirty-nine patients (69.6%) filled out the questionnaires 6 months after surgery. The mean maximum flow rate, PVR, lower urinary tract symptoms (LUTS)-total score, LUTS-specific quality of life, and EuroQol-visual analog scale scores improved significantly from 3.8 mL/s, 77.6 mL, 12.9, 2.6, and 53.6 at baseline to 17.6 mL/s, 21.3 mL, 4.1, 0.9, and 74.9 postoperatively (p = 0.003, p = 0.004, p = 0.005, p < 0.0001, p < 0.0001, respectively). The SHIM score did not change significantly (from 2.6 at baseline to 2.3 postoperatively; p = 0.59). As for patient satisfaction, 84.6% of patients (33/39) were "satisfied" (46.1%) or "very satisfied" (38.5%) with the outcome. CONCLUSIONS: PU had a high surgical success rate, and significantly improved patients' subjective symptoms and achieved a high level of satisfaction.

Successful engraftment of epithelial cells derived from autologous rabbit buccal mucosal tissue, encapsulated in a polymer scaffold in a rabbit model of a urethral stricture, transplanted using the transurethral approach.

BACKGROUND: A pilot study reported an autologous buccal mucosal cell transplant in humans through the trans-urethral route using the buccal epithelium expanded and encapsulated in scaffold-hybrid approach to urethral stricture (BEES-HAUS), a minimally invasive approach to treat urethral stricture. Although successful outcomes were achieved in that study, for further validation, it is essential to prove that the transplanted buccal epithelium was engrafted over the urothelium through histological examination of the urethra, harvested post-transplant, which is infeasible in humans. Herein, we report the successful creation of an animal model of urethral stricture and the engraftment of epithelial cells derived from autologous buccal mucosal tissue, encapsulated in a thermo-reversible gelation polymer (TGP) scaffold, transplanted by trans-urethral route. METHODS: An animal model of urethral stricture was created in Japanese white male rabbits using electro-coagulation. Buccal tissue was harvested from the rabbits and subjected to enzyme digestion, followed by 5-7 days of in vitro culture in conventional two-dimensional (2D) culture and in a 3D platform of thermo-reversible gelation polymer (3D-TGP) culture. The cells harvested from the groups were mixed and encapsulated and transplanted with TGP, by transurethral catheterization. Fourteen days later, the urethra was harvested and subjected to histological examination. The buccal biopsy tissue, cells after digestion and cells post-culture were also subjected to histological examination. Urethrogram and endoscopy images were recorded at different time points. RESULTS: The stricture was successfully created, with the coagulated area markedly stenosed. Histological staining of the cells after in vitro processing showed that the cells grew with native epithelial and rounded cell morphology in 3D-TGP while they differentiated into fibroblast like-cells in 2D culture. Histological staining of the urethral tissue after transplantation revealed the engraftment of the transplanted buccal mucosal cells, with stratified squamous epithelium over the specialized stratified urothelium in the urethrotomy site. CONCLUSION: We used histology to prove the successful engraftment of TGP-encapsulated buccal mucosal epithelial cells in an animal model of urethral injury with healing of the injured tissue. The model of urethral stricture and cell therapy, using a transurethral approach, recapitulates the previously reported BEES-HAUS approach and lays the foundation for larger multi-centric translational clinical studies.

Triangular extension of hinge flaps: A novel technique to resolve stomal stenosis and prevent restenosis in staged buccal mucosal urethroplasty.

OBJECTIVES: To verify the utility of triangular extension of a hinge flap in buccal mucosal staged urethroplasty to resolve stomal stenosis after the first stage and ultimately prevent restenosis. METHODS: A total of 23 patients (triangular extension group) were studied in 2013-2019. In the first stage, buccal mucosa was transplanted, and an extended triangle portion of the mucosa was placed beside the proximal and/or distal stoma that was created when the stricture segment of the urethra was resected. In the second stage, during tubularization of the urethral plate, an incision was made at the stoma to increase the caliber to which the triangular extension was inserted. The procedure was considered successful when a 17-Fr flexible cystoscope passed through the reconstructed urethra at 6 months after the second-stage urethroplasty and no additional surgery or bougie dilation required. The clinical course of the triangular extension group was compared with 24 patients who underwent conventional staged urethroplasty (control group). RESULTS: In total, 20 patients from each group underwent second-stage surgery. No patients in the triangular extension group required additional revision surgery because of stomal stenosis after first-stage surgery, whereas five (20%) control patients did. Urethroplasty was successful in 19 patients (95%) in the triangular extension group and in 19 patients (95%) in the control group. Uroflowmetry after the second-stage surgery indicated that the mean maximum urinary flow rate was 21.5 and 15.8 mL/s after triangular extension and the control procedure, respectively (P = 0.027). CONCLUSIONS: The triangular extension technique reduces the need for revision surgery and prevents postoperative restenosis.

A 3D Polymer Scaffold Platform for Enhanced in vitro Culture of Human & Rabbit Buccal Epithelial Cells for Cell Therapies.

BACKGROUND: Buccal mucosal epithelial cells show promising application for various regenerative medicine approaches. In this study, we examined the feasibility of culturing rabbit and human buccal mucosal epithelial cells in a novel thermoreversible gelation polymer (TGP) scaffold, without feeder layers or other foreign proteins. METHODS & RESULTS: The results of this 28-day in vitro culture, u sing the conventional technique (2D) and TGP (3D) showed that the epithelial cell morphology could be maintained only in the TGP group while cells in the 2D group de-differentiated to fibroblast morphology in both human and rabbit samples. CK3 expression, a marker for epithelial differentiation was higher in 3D-TGP cultured cells than 2D. CONCLUSION: TGP based in vitro cell culture is a prospective methodology to culture buccal mucosal epithelial cells efficiently without using foreign biological components for tissue engineering applications.