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.

Our tubularized incised plate urethroplasty Repair. Results for Hypospadias Surgery

Background: The Tubularized Incised Urethral Plate (TIP) urethroplasty is a widely accepted technique among urologists and heavily used in their centers. This technique was developed by Snodgrass in 1994 for repairing varied degrees of hypospadias. Aim: This paper aims at analyzing and evaluating our early experience and the outcomes of using TIP urethroplasty technique. Therefore, the results have to be assessed in a large series. Methods: In this prospective study, 95 patients with varying hypospadiac meatus levels who experienced the procedure of TIP. During the entire sampling period, patients had varying degrees of hypospadias ranging from glanular to penoscrotal (glanular 2, coronal/subcoronal 37, distal shaft 30, mid-shaft 10, proximal shaft 5 and penoscrotal 11). Results: The overall success rate of TIP procedure repair of hypospadias was 87.4%; whereas the overall reoperation rate was 12.6%. The highest percentage was for those with failed previous repair (secondary). The average duration of the procedure was 58.6±18.4 minutes. Nearly a third of the patients developed one or more postoperative major complication. The total rate of fistula was 12.6%, with "10.6% in primary distal, 15.9% in primary proximal and 20% in secondary repair". Sixteen cases had a mild degree of "meatal stenosis" (16.8%), but all were managed by simple dilatation at the office or at home using 8 F feedingtube. Conclusion: The outcomes demonstrated that the TIP procedure is a quick, safe and reliable technique. Additionally, it can provide excellent cosmoses and function with few complications and acceptable reoperation rate.

Management of long segment anterior urethral stricture (≥ 8cm) using buccal mucosal (BM) graft and penile skin (PS) flap: outcome and predictors of failure

ABSTRACT Purpose To evaluate the surgical outcome and predictors of failure of substitution urethroplasty using either dorsal onlay buccal mucosal (BM) graft or ventral onlay penile skin flap (PS) for anterior urethral stricture ≥ 8cm. Patients and methods Between March 2010 and January 2016, 50 patients with anterior urethral stricture ≥ 8 cm were treated at our hospital. The surgical outcome and success rate were assessed. The predictors of failure were analyzed using multivariate analysis. Failure was considered when subsequent urethrotomy or urethroplasty were needed. Results Dorsal onlay BM graft was carried out in 24 patients, while PS urethroplasty in 26 patients. There was no significant difference between both groups regarding patients demographics, stricture characteristics or follow-up period. One case in the BM group was lost during follow-up. Stricture recurrence was detected in 7 (30.4%) patients out of BM group while in 6 (23.1%) patients out of PS group (p value= 0.5). No significant differences between both groups regarding overall early and late complications were observed. Occurrence of early complications and the stricture length were the only predictors of failure in univariate analysis, while in multivariate analysis the occurrence of early complications was only significant. Conclusion On short-term follow-up, both dorsal onlay BM graft and ventral onlay PS flap urethroplasty have similar success rates. However, BM graft has a potential advantage to reduce operative time and is also technically easier. The surgeon should avoid early local complications as they represent a higher risk for failure.

Stereological and biochemical analysis of the urethral edges in patients submitted to end-to-end anastomosis for bulbar urethral stricture

PURPOSE: To study the morphologic alterations in the proximal and distal urethral edges from patients submitted to end-to-end bulbar urethroplasty. MATERIALS AND METHODS: We analyzed 12 patients submitted to anastomotic urethroplasty to treat bulbar strictures less than 2.0 cm in length. After excision of the fibrotic segment to a 28Fr urethral caliber, we obtained biopsies from the spongious tissue of the free edges (proximal: PROX and distal: DIST). Controls included normal bulbar urethras obtained from autopsies of 10 age matched individuals. The samples were histologically processed for smooth muscle cells (SMC), elastic system fibers and collagen. Stereological analysis was performed to determine the volumetric density (Vv) of each element. Also, a biochemical analysis was performed to quantify the total collagen content. RESULTS: Vv of SMC was reduced in PROX (31.48 ± 7.01 p < 0.05) and similar in DIST when compared to controls (55.65 ± 9.60%) with no statistical difference. Elastic fibers were increased in PROX (25.70 ± 3.21%; p < 0.05) and were similar to controls in DIST (15.87 ± 4.26%). Total collagen concentration in PROX (46.39 ± 8.20 μg/mg), and DIST (47.96 ± 9.42 μg/mg) did not differ from controls (48.85 ± 6.91 μg/mg). Type III collagen was similarly present in all samples. CONCLUSIONS: After excision of the stenotic segment to a caliber of 28Fr, the exposed and macroscopically normal urethral edges may present altered amounts of elastic fibers and SMC, but are free from fibrotic tissue. When excising the peri-stenotic tissue, the surgeon should be more careful in the proximal end, which is the most altered.

Caracterização histológica das margens em pacientes submetidos a uretroplastia anastomótica bulbar / Histological characterization of the urethral margins in patients undergoing anastomotic urethroplasty bulbar

Objetivo: A realização meticulosa de uma incisão ou excisão do segmento estenosado e da esponjofibrose associada tanto proximal quanto distal é critica para o sucesso da uretroplastia anterior. Entretanto, a normalidade das margens da uretra estenosada são determinadas durante o procedimento cirúrgico, baseadas apenas no aspecto macroscópico do tecido. Estudos microscópicos avaliando as margens normais não foram encontrados na literatura. O objetivo deste trabalho é caracterizar o aspecto histológico das margens supostamente normais da estenose da uretra masculina e o efeito causado pela realização de uma cistostomia suprapúbica, na microestrutura da extremidade uretral proximal à estenose. Materiais e Método: As amostras foram obtidas de 29 pacientes com média de idade de 40,3 anos, variando de 20 a 65 anos, que foram submetidos à uretroplastia bulbar término-terminal. Depois que o segmento estenosado foi removido, foram realizadas biópsias das extremidades supostamente sadias (proximais e distais). A caracterização estrutural foi realizada pelas seguintes colorações histológicas: Hematoxilina e Eosina, tricrômico de Masson, resorcina-fucsina de Weigert, e picrosirius polarizado. Pelo menos um mês antes da uretroplastia, foi realizada uma cistostomia suprapúbica em 15 pacientes (52%). O grupo controle consistiu de 10 uretras bulbares obtidas de cadáveres frescos, macroscopicamente normais, com média de idade de 24,7 anos (entre 21 e 32 anos). Resultados: A estenose de uretra se decorreu da retração cicatricial do tecido fibroso que ocupou os seios vasculares do corpo esponjoso. Este tecido foi constituído por uma matriz extracelular (MEC) densa em todos os pacientes. A MEC foi constituída, na sua maioria, principalmente por colágeno e fibras elásticas. Nenhum paciente apresentou as margens uretrais normais. Todas as extremidades apresentaram alterações microscópicas agudas e/ou crônicas quando comparadas ao grupo controle...

Purpose: Meticulous incision or excision of the stenotic segment and any associated proximal and distal spongiofibrosis is critical to the reliable success of urethroplasty procedures. However, normal urethral limits are determined during surgical reconstruction based on macroscopic aspects only. To our knowledge, microscopic studies evaluating the normal urethral ends have not been done. We aimed to describe the histological pattern of the presumed healthy limits of the urethral stricture disease, and the effect of a suprapubic urinary diversion on the proximal urethral end. Materials and Methods: Samples were obtained from 29 patients 20 to 65 years old (mean age 40.3) who underwent end-to-end bulbar urethroplasty. After urethral strictured segments were excised, biopsies of the presumed healthy ends (proximal and distal) were performed. Structural characterization was evaluated by staining histological sections in Haematoxylin-Eosin, Masson's trichrome, Weigert's resorcin-fuchsin method, and picrosirius-polarization method. At least one month before urethroplasty, suprapubic urinary diversion was performed in fifteen (52%) patients. The control group consisted of 10 bulbar urethras obtained from fresh, macroscopically normal cadavers 21 to 32 years old (mean age 24.7). Results: Urethral strictures were due to contraction of the fibrous tissue which has begun to replace the normal structures of the corpus spongiosum. A replacement of the vascular sinusoids in the corpus spongiosum by a dense extracellular matrix (ECM) occurred in all patients. ECM was formed mainly by collagen (vast majority of them) and elastic fibers. No patient presented microscopic normal urethral ends. All urethral edges presented chronic and/or acute microscopic changes if compared to the control group. With regard to the proximal end, the deposit of ECM presented high cellular density in 18 (62.1%) cases. These cells were predominantly fibroblast and inflammatory cells...

Fibrosis in tubularized skin flaps in rats, using silicon catheters with two different degrees of flexibility: experimental model / Fibrose em retalhos tubulizados de pele de ratos usando cateteres de diferentes flexibilidades como molde: modelo experimental

PURPOSE: Microscopically evaluate the intensity of fibrosis in tubularized skin flaps on the back of Wistar rats, using silicon molds with different degrees of flexibility. METHODS: Twenty rats were submitted to three tubularized skin flaps on their backs. In two tubular flaps, we placed, as a mold, silicon catheters with different degrees of flexibility and removed them on the seventh day after the surgery. They were divided into two groups and euthanized, on the seventh and twenty-first days respectively after the surgery for the collection of the pieces, coloration with Masson tricromic, quantification of the area of each sample and comparison among the groups. RESULTS: Fibrosis was less intense on the tubular flaps where a catheter was not used as a mold. No significant difference was verified among the pieces with the silicon catheters, but there was a tendency of less fibrosis on the tubules with the most flexible catheter. CONCLUSION: There was no significant difference among the two catheter types. Fibrosis was less intense in the flaps where the mold was not used.

OBJETIVO: Avaliar microscopicamente a intensidade da fibrose em retalhos tubulares de pele do dorso de ratos Wistar em uso de moldes de silicone de diferentes flexibilidades. MÉTODOS: Vinte animais foram submetidos à confecção de três retalhos tubulizados de pele na região dorsal. Em dois túbulos foram colocados, como molde, cateteres de silicone com flexibilidades diferentes e retirados no sétimo dia após a cirurgia. Foram divididos em dois grupos e sacrificados, respectivamente, no sétimo e vigésimo primeiro dia após a cirurgia para a coleta das peças, coloração pelo tricrômico de Masson, quantificação da área de cada amostra e comparação entre os grupos. RESULTADOS: A fibrose foi menos intensa nos retalhos tubulares em que não se usou cateter como molde. Não se verificou diferença significativa entre os retalhos com os cateteres de silicone, mas sim, tendência de menos fibrose nos túbulos com cateter mais flexível. CONCLUSÃO: Não houve diferença significativa entre os dois tipos de cateter. A fibrose foi menos intensa nos retalhos onde não se utilizou molde.

Uretroplastia en estenosis uretral severa en la mujer: caso clínico / Urethroplasty in women with severe uretral stenosis: Clinical case

Se describe una técnica de uretroplastia con colgajo vaginal, en una mujer de 70 años con estenosis severa de uretra distal, de etiología no conocida y previamente sometida a múltiples dilataciones y a una uretrotomía interna.

Uretroplastia de aumento con injerto de mucosa bucal / Increase uretroplasy with grafting of buccal mucous

La patología de la estenosis uretral tiene etiología, el tratamiento varía según su ubicación anatómica, extensión y espongiofibrosis. Los tratamientos previos, como la uretrotomía interna (UI), pueden determinar que una estenosis breve se transforme en compleja, con un detrimento en el éxito de curación. Ante estenosis complejas se requiere realizar una uretroplastia. Se revisa la experiencia de uretroplastia con mucosa oral en 20 pacientes: 9 portadores de estenosis bulbar, 3 de uretra peneana y bulbar, 3 peneana, 4 con balanitis xerótica obliterans (BXO) y una panestenosis. La tasa de éxito global de la serie fue de 80 por ciento (16 de 20 pacientes) con un seguimiento promedio de 13,5 meses. El éxito para la estenosis peneana y bulbar fue de 81 por ciento (13 de 16 pacientes). No hubo recidiva de liquen escleroso en la mucosa bucal. No se registraron complicaciones mayores. La uretroplastia de aumento con mucosa oral es una buena opción para estenosis complejas con baja morbilidad.

Uretroplastía de aumento con injerto de mucosa bucal / Augmenting urethroplasty with graft buccal mucosa

La patología de la estenosis uretral tiene diversa etiología, el tratamiento varía según su ubicación anatómica, extensión y espongiofibrosis. Los tratamientos previos como la uretrotomía interna (UI) pueden determinar que una estenosis breve se transforme en compleja, con un detrimento en el éxito de curación. Frente a estenosis complejas que requieren algún tipo de aumento del lumen uretral, ha surgido una tendencia por el uso de mucosa bucal, ya que presenta características favorables (fácil obtención, buen prendimiento y ser cosméticamente aceptable).Se revisa la experiencia de uretroplastía con mucosa oral en 11 pacientes: diez portadores de estenosisbulbar y uno de estenosis anterior secundaria a Balanitis Xerótica Obliterans (BXO).La tasa de éxito fue del 91 porciento (10 de 11 pacientes), con un seguimiento promedio de 10,4 meses. No se registraron complicaciones mayores. La curva de aprendizaje para la obtención de la mucosa bucal es breve y simple. Los injertos libres de mucosa oral son, al menos, igual de buenos que otros materiales para uretroplastía de aumento, con mínimas complicaciones y sin alteración cosmética del pene.