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.

Urethral carcinoma accompanied by urethral stricture due to male genital lichen sclerosus / 中华泌尿外科杂志

Objective:To investigate the characteristics and the management of male genital lichen sclerosus (MGLSc)accompanied by urethral carcinoma.Methods:A retrospective analysis was performed on 16MGLSc accompanied by urethral carcinoma patients who were referred to Shanghai Sixth People’s Hospital between June 2000 and August 2019. The average age was 53.7 (45-69) years. All of the patients had a mean history of MGLSc 15(6-35) years, anterior urethral stricture received urethral dilatation and other inappropriate urethrotomy treatment for 10 (8-15) years. There were 5 cases of solid mass 4.5 (3-7) cm in scrotum, accompanied by obviously pain. There were 11 cases of infective masses 6(4-10)cm in the perineum, and the masses were ulcerated with purulent secretions and residue-like pus mixed with necrotic tissues draining from the wounds. Urethrocutaneous fistula developed in 9 cases, and the secretions in the fistula cannot heal. The diseased tissue was confirmed by pathology as the metastasis of invasive urothelial carcinoma in 12 patients and urethral squamous cell carcinoma in 4 patients. 9 cases of tumor invaded corpus spongiosum or corpus cavernosum, 5 cases invaded corpus spongiosum or corpus cavernosum, with enlarged firm one side inguinal node. 2 cases of tumor invaded corpus cavernosum, beyond prostatic capsule and bladder neck, bilateral palpable inguinal lymph nodes metastasis were found, one case found tumor involved the left testis. 9 cases were T 2-3N 0M 0, 5 cases T 2-3N 1M 0, 1 case T 3N 2M 0, 1 case T 4N 2M 1. 5 patients with substantial tumors located in the scrotum, penile-sparing scrotum tumor, urethral tumor resection and urethrostomy was performed in 2 patients. Partial phallectomy, urethral tumor resection and perineal urethrostomy were performed in 3 patients. 11 patients with urethral cancer complicated with perineal infectious mass, 2 patients underwent extensive resection of the tumor and suprapubic cystostomy. 8 cases with perineal tumor infection complicated with urethrocutaneous fistulas formation, of which 2 patients received perineal mass, urethral tumor, fistula resection and suprapubic cystostomy, 4 patients with unilateral inguinal lymph node metastasis and received perineal mass, urethral tumor, fistula, lymph node resection and suprapubic cystostomy. 2 patients with bilateral inguinal node metastasis underwent total phallectomy and urethrectomy, inguinal lymph node resection and suprapubic cystostomy. One case of perineal infectious mass with urethral cutaneous fistula and unilateral inguinal lymph node metastasis (T 2-3N 1M 0) gave up tumor resection. Results:The pathological examination of surgical resection of the glans and urethra showed typical MGLSc manifestations as epithelial keratinization, basal cell vacuoles degeneration, dermis lymphocyte infiltration. The pathological examination of the surgical excised diseased urethra and surrounding tumor tissue showed invasive urothelial carcinoma in 12 patients. Immunohistochemical staining showed positive expression of P53, Ki-67 and GATA3. 4 patients of urethral squamous carcinoma and immunohistochemical staining showed positive expression of Ki-67, P40 and GATA3. All patients received cisplatin combined with gemcitabine chemotherapy for an average of 4.8 (2-6)courses and received local radiotherapy (50-70Gy/5w). The mean postoperative survival time of the 16 patients was 26 (3-48) months, and the survival time of urethral transitional cell carcinoma and squamous cell carcinoma was 29 (18-48) months and 18 (3-24) months, respectively. All patients died of tumor metastasis, with 6 patients of lung metastsis, 2 patients of lumbar and bone metastasis, 3 patients of liver metastasis, 2 patients of brain metastasis and 3 patients of lung combined with bone metastasis.Conclusions:MGLSc can cause urethal stricture and urethral carcinoma. The clinical manifestations are dysuria, urinary tumor, repeated infection and urethral fistula. Tumor excision and urinary diversion are common surgical methods. Urethral transitional cell carcinoma and squamous cell carcinoma are common pathological types. Postoperative combined radiotherapy and chemotherapy can be used, but the overall prognosis is poor.

The efficacy of non-transecting uerthroplasty in the management of bulbar urethral stricture / 中华泌尿外科杂志

Objective:To compare efficacy and erectile function outcome of Non-transecting Urethroplasty (NTU)with excision and primary anastomotic urethroplasty(EPA) in the management of bulbar urethral stricture.Method:A retrospective analysis of the case data of 73 patients with bulbar urethral stricture admitted to Shanghai Sixth People's Hospital from January 2016 to December 2019. The patients are 18 to 60 years old, because of the stenosis of the bulbous urethra, the length of the stenosis is less than 2 cm, and there is no history of urethral surgery, no multiple urethral stricture, and no obvious ED before surgery. According to the operation method, the patients were divided into 25 cases in NTU group and 48 cases in EPA group. The ages of the NTU group and the EPA group were (39.2±9.4) years and (42.1±9.3) years, respectively. The course of the disease was 6.0(3.0-14.0) months and 6.5(3.0-11.0) months, respectively, and the body mass index was (23.7±3.2) kg/m 2 and (24.5±2.7) kg/m 2, the preoperative maximum urine flow rate (Q max) was (8.7±4.3) ml/s and (7.9±4.6) ml/s, respectively, and the length of the stenosis was respectively (1.7±0.4) cm and (1.8±0.2) cm, the preoperative International Erectile Function Questionnaire (IIEF-5) was (20.9±1.9) points and (21.3±2.1) points, respectively, the difference was not statistically significant ( P>0.05). The etiology of NTU group and EPA group were 8 cases (32.0%) and 31 cases (64.6%) of trauma, 11 cases (44.0%) and 9 cases (18.8%) of iatrogenic injury, and 6 cases (24.0%) and 8 cases (16.7%), the difference was statistically significant ( P=0.023). All operations were performed by the same team of doctors. The urethral scar was assessed during the operation. If the scar tissue can be completely removed without breaking the urethra, NTU is performed. The distal end of the urethra is cut at the dorsal side of the narrow segment of the urethra, and the urethral scar is removed in a transverse wedge shape. The urethra is sutured; otherwise, EPA is performed, the urethra is completely cut off, the stricture of the urethra and surrounding scar tissue is completely removed, and the urethra end-to-end anastomosis is performed. Record the operation time and intraoperative bleeding. Difficulty urinating after surgery, urethral microscopy and urethral angiography showed that the urethral stricture at the surgical site was defined as a failure of the operation. The urinary catheter was removed 3 weeks after surgery, urine flow rate was measured at 3 weeks, 6 months, and 12 months after surgery, erectile function was evaluated 12 months after surgery, and urethral angiography was performed 1 to 2 years after surgery. Result:All 73 operations in this study were successfully completed. The operation time of NTU group and EPA group were (67.6±11.3) min and (62.7±10.1) min, respectively, and the difference was not statistically significant ( P=0.063); intraoperative blood loss was (71.6±16.2) ml and (86.0±20.8) ml, the difference was statistically significant ( P=0.004). The postoperative median follow-up time was 18.0 months (13-38 months). The surgical success rates of the NTU group and EPA group were 92.0%(23/25) and 93.8%(45/48), respectively. The Q max of the NTU group and the EPA group were (26.7±3.6) ml/s and (28.1±8.7) ml/s, (25.2±3.5) ml/s and (26.7±8.1) ml/s, (25.0±4.3) ml/s and (26.2±7.2) ml/s; the IIEF-5 scores were (21.8±1.6) and (20.6±2.9) points respectively at 12 months after operation, the difference was both No statistical significance ( P>0.05). There was a statistically significant difference in IIEF-5 between NTU group and preoperative ( P=0.023). Conclusion:NTU can achieve the same outcomes as EPA in the management of bulbar urethral stricture. More importantly, the continuance of bulbar urethra is attained and avoiding rupture of bulbar cavernous artery, so as to protect the blood supply of penile and erectile function. NTU is a minimally invasive, feasible surgical method, which is advised for the patients with shorter stricture segment and fewer fibrosis.

Clinical application and pain tolerance of lfexible cystoscopy in pelvic fracture urethral distraction defects stricture / 中国内镜杂志

Objective To study the value of flexible cystoscopy in diagnosing posterior urethral strictures resulting from pelvic fracture and the pain score of the examination. Methods Between 2014 and 2015, 120 male patients with pelvic fracture urethral distraction defect were evaluated by cystoscopy before surgery. In this study, flexible cystoscopy was used in 87 patients, 33 patients received conventional rigid cystoscopy. The cystoscopy was introduced into the posterior urethra and the area was evaluated for the length of the proximal urethra and any possible fistulas, false passages, calculi or displacement of the posterior urethra. The patient’s pain feeling was recorded during the examination, 24 hrs after cystoscopy examination. The pain feeling result was achieved by visual analogue pain scale. Results Severe allergic reaction or obvious discomfort did not occur in any patients after cystoscopy. By comparing the data obtained from lfexible cystoscopy to those from conventional urethrography, the rate of detection in other abnormalities was higher in lfexible cystoscopy than in conventional urethrography. 21, 5, 7 and 5 patients were detected with calculus, posterior urethral structure damage, false passage and ifstula respectively. In comparison, the abnormalities were only observed in 3, 2, 3 and 1 patients respectively through conventional urethrography imaging. However, the pain feeling of the flexible cystoscopy is better than the convenional rigid cystoscopy. The statistical difference was found in the pain feeling score during the examination and later after the examination. Conclusions Flexible cystoscopy is a safe and valuable procedure in the evaluation of the posterior urethra in patients with pelvic fracture urethral distraction defect before surgery.