Urethral carcinoma after skin substitution urethral reconstruction.

Urethral cancer after urethral reconstruction is an under-recognized, uncommon disease associated with significant morbidity and mortality. The survival rates of patients with carcinoma of the bulbar urethra are as low as 20%-30%. Stricture recurrence and unrecognized malignant changes present prior to reconstruction are major risk factors for urethral cancer. Skin substitution urethroplasty is subjected to higher rates of recurrence, which lends to the potential for carcinogenesis. We present a case of a 59-year-old male who underwent multi-stage skin substitution urethroplasty who developed urethral carcinoma 20 years later.

Posterior Sagittal Approach Provides Optimal Exposure for Urethral Reconstruction in Children With a History of Anorectal Malformations.

OBJECTIVE: To present a unique series of children with previously repaired anorectal malformations (ARM) with subsequent urethral pathology repaired via a posterior sagittal exposure and highlight the associated technical advantages. METHODS: Using a retrospective review of all procedures performed in our pediatric colorectal and pelvic reconstruction program from January 2020 through December 2022, we compiled a case series of patients with a history of ARM and prior posterior sagittal anorectoplasty (PSARP) who had urethral pathology and concurrent indication for redo-PSARP. Clinical features, operative details, and postoperative outcomes were collected. RESULTS: Six male patients presented at a median age of 4.3 years, all born with an ARM of recto-urinary fistula type, of which 3 were recto-prostatic, 1 recto-bladder-neck, and 2 unknown type. In addition to redo-PSARP, 2 underwent remnant of the original fistula excision and 4 had urethral stricture repair. One required post-operative Heineke-Mikulicz anoplasty. Patients underwent cystoscopy 4-6 weeks post-reconstruction, and none showed urethral stricture requiring treatment. Post-procedurally, 5 patients were able to void urethrally and 1 required additional bladder augmentation/Mitrofanoff. CONCLUSION: Redo-PSARP completely mobilizes the rectum, thereby providing excellent exposure to the posterior urethra for repair. This approach also allows the option of a rectal flap for augmented urethroplasty as well as harvest of an ischiorectal fat pad for interposition.

Photodynamic therapy for male genital lichen sclerosus with urethral stricture-Case report.

Male genital lichen sclerosus (MGLSc) typically impacts the external genitalia, resulting in balanitis, erectile pain, urination symptoms, and/or urinary retention. Urethral stricture develops in up to 20 % of these patients, which is usually found in the distal part of the urethra but can, in severe instances, impact the entire urethra and cause structural changes. Patients with skin lesions limited to the foreskin and partially extending to the glans can typically be cured by circumcision, but the recurrence rate of stricture is high when the glans or urethra is extensively involved. In the following case report, we describe a 45-year-old man with a history of MGLSc for 3 years and urethral stricture for 2 years, and these conditions remained untreated after circumcision. We emphasize that treatment with 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) may further improve outcomes in such severe cases.

Extracellular matrix analysis of fibrosis: A step towards tissue engineering for urethral stricture disease.

The urogenital tract is a target for many congenital and acquired diseases, both benign and oncogenic. In males, the urethra that transports urine and semen can be obstructed by a fibrotic disease called urethral stricture disease (USD). In severe USD, the whole organ including the vascular embedding, the corpus spongiosum (CS), is affected. Recurrent or severe USD is treated by reconstructive surgery. Tissue engineering may improve the outcome of urethral reconstruction in patients with complicated USD. Currently in urethral reconstruction only the epithelial layer is replaced, no substitution for the CS is provided, while the CS is important for mechanical support and vascularization. To develop a tissue engineering strategy for the CS, it is necessary to know the protein composition of the CS. As the extracellular matrix (ECM) plays an important role in the formation of fibrosis, we analyzed the distribution and localization of ECM components in human healthy and fibrotic CS tissue using immunohistology. The morphology of components of the elastic network were affected in USD. After decellularization a clear enrichment of proteins belonging to the ECM was found. In the proteomic analysis collagens COL15A1 and COL4A2 as well as inter-alpha-trypsin inhibitor ITIH4 were upregulated in fibrotic samples. The glycoproteins Periostin (POSTN), Microfibrillar-associated protein 5 (MFAP5) and EMILIN2 are downregulated in fibrotic tissue. To our knowledge this is the first proteomic study of ECM proteins of the CS in healthy and in USD. With these results a regenerating approach for tissue engineered CS can be developed, including relevant ECM proteins that reduce fibrosis and promote healthy healing in urethral reconstructive surgery.

Comparison of oral morbidity and mid-term efficacy of anterior urethroplasty using an autologous tissue-engineered graft (MukoCell®) versus native oral mucosa graft.

OBJECTIVE: Our study aimed to compare surgical success rate (SR) and oral morbidity of augmentation urethroplasty for anterior urethral strictures using autologous tissue-engineered oral mucosa graft (TEOMG) named MukoCell® versus native oral mucosa graft (NOMG). METHODS: We conducted a single-institution observational study on patients undergoing TEOMG and NOMG urethroplasty for anterior urethral strictures >2 cm in length from January 2016 to July 2020. SR, oral morbidity, and potential risk factors of recurrence were compared between groups were analyzed. A decrease of maximum uroflow rate < 15 mL/s or further instrumentation was considered a failure. RESULTS: Overall, TEOMG (n = 77) and NOMG (n = 76) groups had comparable SR (68.8% vs. 78.9%, p = 0.155) after a median follow-up of 52 (interquartile range [IQR] 45-60) months for TEOMG and 53.5 (IQR 43-58) months for NOMG. Subgroup analysis revealed comparable SR according to surgical technique, stricture localization, and length. Only following repetitive urethral dilatations, TEOMG achieved lower SR (31.3% vs. 81.3%, p = 0.003). Surgical time was significantly shorter by TEOMG use (median 104 vs. 182 min, p < 0.001). Oral morbidity and the associated "burden" in patients' quality of life were significantly less at 3 weeks following the biopsy required for TEOMG manufacture, compared to NOMG harvesting and totally absent at 6 and 12 months postoperatively. CONCLUSIONS: The SR of TEOMG urethroplasty appeared to be comparable to NOMG at a mid-term follow-up but taking into account the uneven distribution of stricture site and the surgical techniques used in both groups. Surgical time was significantly shortened, since no intraoperative mucosa harvesting was required, and oral complications were diminished through the preoperative biopsy for MukoCell® manufacture.

Rectifying disorder of extracellular matrix to suppress urethral stricture by protein nanofilm-controlled drug delivery from urinary catheter.

Urethral stricture secondary to urethral injury, afflicting both patients and urologists, is initiated by excessive deposition of extracellular matrix in the submucosal and periurethral tissues. Although various anti-fibrotic drugs have been applied to urethral stricture by irrigation or submucosal injection, their clinical feasibility and effectiveness are limited. Here, to target the pathological state of the extracellular matrix, we design a protein-based nanofilm-controlled drug delivery system and assemble it on the catheter. This approach, which integrates excellent anti-biofilm properties with stable and controlled drug delivery for tens of days in one step, ensures optimal efficacy and negligible side effects while preventing biofilm-related infections. In a rabbit model of urethral injury, the anti-fibrotic catheter maintains extracellular matrix homeostasis by reducing fibroblast-derived collagen production and enhancing metalloproteinase 1-induced collagen degradation, resulting in a greater improvement in lumen stenosis than other topical therapies for urethral stricture prevention. Such facilely fabricated biocompatible coating with antibacterial contamination and sustained-drug-release functionality could not only benefit populations at high risk of urethral stricture but also serve as an advanced paradigm for a range of biomedical applications.

Is colorectal mucosa a reasonable graft alternative to buccal grafts for urethroplasty?: A comparison of graft histology and stretch.

OBJECTIVE: To compare the histological properties and stretch of colorectal mucosal grafts (CMG) and buccal mucosal grafts (BMG) and to evaluate the impact of age, medical comorbidity and tobacco use on these metrics. MATERIALS AND METHODS: Samples of BMGs from patients undergoing augmentation urethroplasty were sent for pathologic review. CMGs were collected from patients undergoing elective colectomy. CMGs were harvested fresh, at full thickness from normal rectum/sigmoid. Patients with inflammatory bowel disease, prior radiation, or chemotherapy were excluded. RESULTS: Seventy two BMGs and 53 CMGs were reviewed. While BMGs and CMGs were both histologically composed of mucosal (epithelium + lamina propria) and submucosal layers, the mucosal layer in CMG had crypts. The outer epithelial layers differed significantly in mean thickness (BMG 573µm vs. CMG 430µm, p=0.0001). Mean lamina propria thickness and submucosal layer thickness also differed significantly (BMG 135µm vs. CMG 400µm, p<0.0001; BMG 1090µm vs. CMG 808µm, p = 0.007, respectively). Mean delta stretch, as to length and width, was greater for CMG (118% x 72%) compared to BMGs (22% x 8%), both p<0.001. CONCLUSION: CMGs and BMGs significantly differ histologically in layer composition, width and architecture, as well as graft stretch. Given its elastic properties, CMG may be useful in covering large surface areas, but its thin epithelium, thick lamina propria and additional muscularis mucosal layer could impact graft take and contracture.

Deciphering the Role of TGF-ß1 in Altering Collagen I and Collagen III in the New Zealand Rabbit's (Oryctolagus cuniculus) Urethral Wall in Urethral Stricture Development.

Background: Presently, there's a lack of standardization in animal models used for studying urethral stricture. Transforming Growth Factor Beta 1 (TGF-ß1) is known to regulate the deposition of extracellular matrix in both normal and pathological conditions. This factor holds promise as a potential model for simulating urethral stricture. Objective: This study aims to investigate the impact of Transforming Growth Factor Beta 1 (TGF-ß1) on Collagen I and Collagen III within the urethral wall of New Zealand Rabbits (Oryctolagus cuniculus) in the context of developing urethral stricture in animal models. Methods: We conducted genuine laboratory experiments using Male New Zealand rabbits (Oryctolagus cuniculus), which were categorized into five groups: control, placebo, and three treatment groups (TGF-ß1 injections of 1 µg, 2 µg, 4 µg). After a duration of 6 weeks, we conducted urethrography, histopathological analysis, and assessed the formation of collagen I and collagen III within the urethral wall. Results: Elevating the dosage of TGF-ß1 led to a reduction in the average urethral lumen diameter of rabbits (29.3% in the 2µg group and 34% in the 4µg group) compared to the control group. In fact, three rabbits experienced a decrease of ≤ 50% in their urethral lumen diameter. As the doses of TGF-ß1 increased, we observed significant increases in the density of collagen I, and collagen III in both the periluminal and peripheral regions of the urethral spongiosum. Additionally, there was a tendency for the collagen I/collagen III ratio to decrease in the periluminal region, with collagen III density surpassing that of collagen I. In the peripheral spongiosa area, notable mean differences were observed between the control group, 1T, and 2T groups, with collagen I density tending to be higher than that of collagen III. Furthermore, the percentage of urethral lumen diameter exhibited a robust negative correlation with periluminal collagen I density (r = -0.672, p = 0.001), peripheral spongiosa collagen I density (r = -0.603, p = 0.005), periluminal collagen III density (r = -0.717, p = 0.001), and an exceptionally strong negative correlation with collagen III density of peripheral spongiosa (r = -0.804, p = 0.000). Conclusion: TGF-ß1 exerts an influence on altering the composition of collagen I and collagen III within the urethral wall of rabbits, leading to a reduction in the diameter of the urethral lumen. Further research is warranted to determine the optimal dose of TGF-ß1 required to induce urethral stricture effectively.

Urethral Cancer After Urethroplasty: A Case Report and Review of the Literature.

OBJECTIVE: To review and report data on transformation to urethral carcinoma after urethroplasty for urethral stricture disease. Primary urethral carcinoma is a rare entity, and guidelines lack high quality data from which to cite. Urethroplasty is a highly effective treatment for urethral stricture disease, though in rare cases complications may include development of urethral carcinoma. METHODS: A systematic PubMed search was performed to identify all articles describing patients with urethral carcinoma after urethroplasty. Data were collected on the following parameters: patient age and sex, indication for urethroplasty, presentation of cancer, imaging, pathology, presence of metastasis, intervention, and outcome. RESULTS: The final cohort included fourteen patients, 13 from previously published cases and one from our institution. The median patient age at presentation was 60, most had endoscopic management prior to urethroplasty, and the majority presented with decreased urinary stream. All patients developed squamous cell carcinoma of the urethra. Patients underwent radical resection, lymph node dissection, chemotherapy, or radiotherapy, often in combination. A majority of patients had died at the time of case report. CONCLUSION: Development of urethral squamous cell carcinoma, particularly after urethroplasty, is a rarely encountered process. Patients and urologists must have a high index of suspicion and investigate symptoms such as fistula or lower urinary tract symptoms, even if these occur many months or even years after buccal mucosa graft . By compiling previously reported cases and adding an additional case to the literature, we hope that familiarity with this entity will lead to earlier recognition and diagnosis of disease.

Circ_0047339 promotes the activation of fibroblasts and affects the development of urethral stricture by targeting the miR-4691-5p/TSP-1 axis.

Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the regulatory mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The results of circRNA microarray showed that there were 296 differentially expressed genes between urethral scar tissue and normal urethral tissue. The enrichment analysis of Kyoto encyclopedia of genes and genomes showed that these circRNAs were significantly correlated with ECM-receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA-miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expressions of Collagen I (COL-1) and α-smooth muscle actin (α-SMA) also reduced. As a competing endogenous RNA, circ_0047339 could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Our results showed that circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through miR-4691-5p/TSP-1 axis, thus promoting the development of urethral stricture.

[Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-ß1 signaling and inflammatory response].

OBJECTIVE: To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism. METHODS: Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-ß1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1ß were detected using qRT-PCR. RESULTS: The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-ß1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1ß in the injured urethral tissue (P < 0.05 or 0.01). CONCLUSION: Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-ß1 pathway and inflammatory response.

The Effects and Mechanisms of the Rapamycin-eluting Stent in Urethral Stricture Prevention in Rabbits.

Background: Rapamycin was shown to reduce transforming growth factor ß1 (TGF-ß1) expression, inhibit the Mammalian target of rapamycin function, and prevent TGF-ß1-induced pulmonary fibrosis. Rapamycin-eluting stents (RES) were successfully used to prevent coronary artery restenosis. Urethral stricture is one of the most challenging problems in urology. Thus, combining the pharmacological effects of rapamycin and the mechanical support of the stent on the urethra may prevent urethral stricture formation. However, the use of RES for urethral stricture treatment has not been studied. Aims: To observe the effects of RES in urethral stricture in a rabbit model. Study Design: Animal experimentation. Methods: Twenty adult male New Zealand rabbits were randomly divided into control, urethral stricture model, bare-metal stent, and RES groups. The rabbits in the control group underwent urethroscopy alone without electrocoagulation. The rabbit model of urethral stricture was established by electrocoagulation using a self-made electrocoagulation device under direct vision using ureteroscopy. After model establishment, the rabbits in the bare-metal stent and RES groups received stent placement by ureteroscopy. On day 30, retrograde urethrography was performed to assess urethral stricture formation, ureteroscopy to remove the stents, and histological examinations to assess the degree of fibrosis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to evaluate the expression levels of TGF-ß1, Smad3, and matrix metalloproteinase 1 (MMP1). Results: Urethral stricture formation was seen in the model group, whereas not in the bare-metal stent group. The bare-metal stents did not displace but were difficult to remove. In the RES group, RES was dislodged in itself at postoperative day 27 in one rabbit, whereas successfully removed by ureteroscopy in the remaining four rabbits, and urethral stricture formation was not seen on retrograde urethrography after stent removal. Histological examination revealed a large number of dense fibroblasts and blue-stained collagen fibers in the bare-metal stent group, whereas the number of fibroblasts and collagen fibers under the mucosa was reduced in the RES group. RT-qPCR and Western blot analyses showed that the messenger ribonucleic acid (mRNA) and protein expression of TGF-ß1and Smad3 was significantly decreased, and mRNA and protein expression of MMP1 was significantly increased in the RES group than that in the model ((P < 0.001) and bare-metal stent groups (P < 0.001). Conclusion: RES can effectively prevent electrocoagulation-induced urethral stricture in rabbits. The mechanism may be related to the effect of rapamycin on inhibiting TGF-ß1 and Smad3 expression and promoting MMP1 expression in urethral tissues.

Anterior Urethroplasty for the Management of Urethral Strictures in Males: A Systematic Review.

OBJECTIVE: To identify the currently utilised techniques of anterior urethroplasty described in literature for treatment of urethral strictures, assess the effectiveness of the identified techniques based on re-stricture and complication rates, evaluate, and suggest treatment options based on current evidence for urethral strictures at different locations and of different lengths. METHODS: A systematic review of the MEDLINE, EMBASE, Scopus and Cochrane Library databases from conception up to September 2020 was performed. Primary outcomes included success rates measured via re-stricture rates and the post-operative maximum urinary flow rate (Qmax). Secondary outcomes included patient reported complication rates. RESULTS: A total of 52 papers, including 7 RCTs, met the inclusion criteria. Forty studies described the use of free graft urethroplasty with a median success rate of 86.5% (IQR = 8.1). The best outcomes were found in dorsal onlay buccal mucosa grafting in the penile urethra (86.6%). Twelve described the use of pedicled flap urethroplasty with a median success rate of 76% (IQR = 14.4). Excision and Primary Anastomosis results were reported in 5 studies and showed an overall highest success rate of 89.7% (IQR = 7.0) but involved the shortest strictures of median lengths of 2.1 cm (IQR = 0.48). CONCLUSION: Graft urethroplasty showed optimal outcomes when utilised in penile and bulbar strictures, with dorsal onlay buccal mucosa grafting presenting with the largest evidence base and best outcomes overall. Flap urethroplasty had the highest success rates in panurethral and bulbar strictures, while anastomotic urethroplasty had the greatest success in bulbar and penobulbar strictures.

Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-β1 signaling and inflammatory response / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism.@*METHODS@#Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-β1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1β were detected using qRT-PCR.@*RESULTS@#The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-β1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1β in the injured urethral tissue (P < 0.05 or 0.01).@*CONCLUSION@#Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-β1 pathway and inflammatory response.

Differential expression of miRNAs involved in biological processes responsible for inflammation and immune response in lichen sclerosus urethral stricture disease.

PURPOSE: To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty. METHODS: Urethral stricture tissue was collected from 2005-2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0. RESULTS: In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10). CONCLUSIONS: To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.

Buccal mucosal graft urethroplasty for anterior urethral stricture, experience from a low-income country.

BACKGROUND/PURPOSE: This study was conducted to present our experience in urethral mucosal graft urethroplasty to repair urethral stricture, as the first experience in our context. METHODS: This is a prospective hospital-based study that had been designed to review management outcomes of buccal mucosal graft urethroplasty for anterior urethral stricture from January 2017 to January 2019. RESULTS: The total number of involved patients was 60. The success rate was found to be 90% (n = 54), while 6 (10%) had a recurrence of stricture. Pain and pain combined bleeding from internal suture lines were the only early complication encountered in 50 (83.3%) and 2 (3.3%) patients, respectively. late complications occurred as follows 14 (23.3%) patients had UTI, 12 (20%) had wound infections, 8 (13.3%) had changes in ejaculation, and decrease in intensity of orgasm, and 6 (10%) had erectile dysfunction. One of the long-term complications was graft diverticulum in one case and was treated conservatively (in ventral on lay BMG). CONCLUSION: Improvement of the service in limited resources countries like Sudan and was reflected in the excellent outcome of BMG urethroplasty as treatment of anterior urethral stricture (success rate 90%).

Effects of a gamma-secretase inhibitor of notch signalling on transforming growth factor ß1-induced urethral fibrosis.

Urethral stricture (US) is a common disorder of the lower urinary tract in men caused by fibrosis. The recurrence rate of US is high; however, there are no effective therapies to prevent or treat urethral fibrosis. The pathogenesis of urethral fibrosis involves myofibroblast activation and excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying this pathological activation are not completely understood. It has been demonstrated that Notch signalling contributes to the development of fibrosis and inflammation. However, whether this contributes to urethral fibrosis remains unclear. In this study, activation of Notch signalling was observed in patients with US. Additionally, it was noted that activation of Notch signalling promoted ECM production and myofibroblast activation in human urethral scar fibroblasts (HUSFs) treated with transforming growth factor (TGF) ß1. However, the Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppressed activation of Notch signalling as well as proliferation and migration of the TGFß1-treated HUSFs. Additionally, DAPT ameliorated TGFß1-induced urethral fibrosis in Sprague Dawley rats by suppressing ECM production, myofibroblast activation and the TGFß signalling pathway. These findings demonstrate that Notch signalling may be a promising and potential target in the prevention or treatment of urethral fibrosis.

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.

One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysis.

PURPOSE: Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs. MATERIALS AND METHODS: A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses. RESULTS: Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05). CONCLUSIONS: One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

Extended Primary Anastomosis With Penile Plication (EPAPP): A Promising New Alternative to Perineal Urethrostomy for Reconstruction of Long Urethral Strictures.

OBJECTIVE: At present, excision and primary anastomosis (EPA) urethroplasty is a highly reliable method of reconstruction for short bulbar urethral strictures. Longer strictures are often managed with grafting techniques to ensure a tension-free repair. Here we report our initial experience with a new, extended anastomotic technique for long bulbar strictures that incorporates plication of the ventral corporal bodies to reduce the distance between the urethral ends and obviates the need for grafting. METHODS: We reviewed records for all urethroplasties performed by a single surgeon at our institution between January 2018 and February 2020. We identified a cohort of older patients with complex strictures who underwent Extended Primary Anastomosis with Penile Plication (EPAPP). Patient demographics, stricture characteristics, perioperative 75 parameters, and postoperative outcomes were evaluated. RESULTS: Of 346 urethroplasty records reviewed, 10 patients (2.9%) underwent EPAPP. Mean stricture length was 3.75 ± 1.4 cm. EPAPP patients were older than those repaired by other techniques (mean age 66.6 vs 55.6, P = .024), and most were not sexually active preoperatively. Postoperative voiding cystourethrogram confirmed urethral patency without extravasation in all patients. At a median follow up of 9.7 months (IQR 8.5-11.5) 8 patients remained asymptomatic after EPAPP alone and 2 patients required a single balloon dilation for stricture recurrence. CONCLUSION: EPAPP is a promising alternative option for the management of long bulbar strictures among appropriately selected patients.