Yinglong Sa

The relationship between erectile dysfunction and open urethroplasty: a systematic review and meta-analysis.

INTRODUCTION Various urethroplasty techniques have been used to treat urethral stricture. Whether the patient erectile function is affected by this open surgery is still controversial. AIM The aim of this study is to determine the relationship between erectile function and open urethroplasty. METHODS A systematic review of the literature was performed using Medline, Embase, the Web of Science, and the Cochrane Library databases through October 2012 to identify articles published in any language that examined the effect of open urethroplasty on the risk of erectile dysfunction (ED). This meta-analysis was conducted according to the guidelines for the meta-analysis of observational studies in epidemiology. MAIN OUTCOME MEASURES The incidence of ED after urethroplasty. RESULTS This meta-analysis consisted of 23 cohort studies, which included 1,729 cases. No significant difference was noticed in patients with anterior urethral stricture before or after intervention (odds ratio [OR] = 0.86; 95% confidence interval [CI]: 0.52-1.40; P = 0.53). While statistical difference in the incidence of ED was revealed in patients before and after intervention for a posterior urethral (OR = 2.51; 95% CI: 1.82-3.45; P < 0.001), further comparisons demonstrated that most anterior urethroplasties did not have an obvious effect on patient erectile function. However, it seems that the incidence of ED was higher in the bulbar anastomosis group than in the oral graft urethroplasty group (OR = 0.32 95% CI: 0.11-0.93; P = 0.04). For the posterior urethroplasty, previous operative history did not show a strong relationship with ED. No statistically significant difference in the risk of ED was demonstrated comparing the posterior urethral reconstructive techniques included in this analysis. CONCLUSION The adverse effect of urethroplasty itself on erectile function is limited, as more patients recover erectile function after urethral reconstruction. For anterior urethroplasty, bulbar anastomosis might cause a slightly higher incidence of ED than other operations. For posterior urethroplasty, trauma might be the main cause of ED.

Transperineal bulboprostatic anastomosis in patients with simple traumatic posterior urethral strictures: a retrospective study from a referral urethral center.

OBJECTIVES To evaluate the results of ancillary procedures for posterior urethroplasty and compare them with the severity of urethral stricture. METHODS A total of 301 patients (average age: 36 years) with posterior urethral strictures due to pelvic fracture urethral distraction defects were included in the study. Delayed transperineal bulboprostatic anastomosis was performed 6-24 months (mean 10 months) after pelvic fracture urethral distraction defects. Simple perineal anastomosis: 103 (34.2%) patients (group 1); perineal anastomosis with separation of the corporeal bodies: 89 (29.6%) patients (group 2); perineal anastomosis with inferior pubectomy: 95 (31.6%) patients (group 3); perineal anastomosis with rerouting of the urethra around the corpora cavernosum: 14 (4.7%) patients (group 4). The clinical outcome was considered a failure when any postoperative instrumentation was needed. The primary outcome examined the total success rate of the procedures. The secondary outcome examined the success rate of the procedures according to the ancillary surgical steps. RESULTS Of the 301 delayed transperineal bulboprostatic anastomosis procedures, 263 (87.4%) were successful and 38 (12.6%) were unsuccessful. Simple perineal anastomosis without ancillary procedures reflected an 89.3% success rate, perineal anastomosis with separation of the corporeal body had an 86.5% success rate, perineal anastomosis with inferior pubectomy had an 84.2% success rate, and perineal anastomosis with urethral rerouting had an 85.7% success rate. CONCLUSIONS Corporal splitting, inferior pubectomy, and urethral rerouting are beneficial and useful ancillary procedures in transperineal posterior urethroplasty to achieve tension-free anastomosis.

TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation.

Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT)-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1), Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.

Crosstalk between TGF-β1 and CXCR3 signaling during urethral fibrosis

Urethral fibrosis is an important pathological feature of urethral stricture. TGF-β1 and CXC chemokine receptor 3 (CXCR3) signaling have been reported as the critical pathways involved in the pathology of fibrosis. Here, we collected the urine samples from the patients with recurring urethral stricture, recurring stricture treated by cystostomy, and age- and gender-matched healthy people. ELISA detection revealed that TGF-β1 level was significantly up-regulated for the urethral stricture patients. By contrast, flow cytometry, real-time PCR detection, and immunofluoresecent staining showed that urethral stricture resulted in decreased expression of CXCR3. TGF-β1 treatment could increase cell proliferation and migration ability of urethra fibroblasts, whereas IP-10/CXCR3 signaling showed the opposite effect. Further, we found a crosstalk between TGF-β1 and CXCR3 signaling in the regulation of urethral fibrosis. Thus, pharmacological intervention of TGF-β1 or CXCR3 signaling has a potential as the therapeutic target for the prevention of urethral fibrosis.

Urethral Reconstruction with Small Intestinal Submucosa Seeded with Oral Keratinocytes and TIMP-1 siRNA Transfected Fibroblasts in a Rabbit Model.

Background: To evaluate the effect of tissue inhibitor of metalloproteinase-1 small interfering RNA (TIMP-1 siRNA) transfected fibroblasts (FB) for urethral reconstruction. Materials and Methods: A ventral urethral mucosal defect was created. Substitution urethroplasty was performed with small intestinal submucosa (SIS) alone (8 rabbits, group 1), autogenic oral keratinocytes (OK)-seeded SIS (8 rabbits, group 2) or autogenic OK and TIMP-1 siRNA transfected FB-seeded SIS (8 rabbits, group 3). At 1 and 6 months after surgery (4 rabbits at each time point), retrograde urethrogram and histologic analysis were performed to evaluate the outcomes of urethroplasty. Results: TIMP-1 siRNA transfected FB decreased the secretion of type I collagen. Under retrograde urethrography, 5 rabbits in group 1, 6 in group 2 and 7 in group 3 maintained a wide urethral caliber. Histologically, inflammation and fibrosis were observed at 6 months in group 1. The speed of urothelium, smooth muscle and vessel regeneration in group 3 was faster than that in group 2. Comparison of smooth muscle-to-collagen ratio, epithelial layers, smooth muscle content and microvessel density among three groups revealed a significant increase (p < 0.05). Conclusions: TIMP-1 siRNA transfected FB could be used as a source of seed cell for urethral tissue engineering and could prevent the proliferation of urethral scar tissue.

Anterior Urethra Reconstruction With Lateral Lingual Mucosa Harvesting Technique

OBJECTIVE To describe a new technique for harvesting the long lingual mucosal graft (LMG) to repair the long-segment urethral strictures. METHODS We performed a retrospective observational study of patients from whom LMGs were harvested from the lateral lining of the tongue for the long-segment anterior urethral strictures repair from 2012 to 2014 at the Shanghai Sixth Peoples Hospital. Patients who had 12 months minimum follow-up were included. Patients with incomplete clinical records were excluded. The LMG was applied on the urethra according to the dorsal onlay technique. RESULTS The primary outcome of the study was the postoperative failure-free survival rate. The secondary outcome was the rate of early and late complications at the harvesting site. Success was defined as Qmax >12 ml/s and no postoperative procedures. One hundred and one patients were included. Median stricture length was 7.1 ± 3.6 cm; median LMG length was 7.2 ± 3.6 cm. The success rate was 81.2% with a median follow-up of 23 months. Complications at the donor site had occurred in 41 patients at 6-months follow-up, and persisted in 18 patients at the 12-months follow-up. A bilateral harvest and harvest length were the main factors influencing complication rate (P = .0038 for 6 months and P = .1112 for 12 months). Almost half of donor site complications subsided within 12 months (P = .0018). CONCLUSION In patients requiring long oral grafts >7 cm to repair anterior strictures, a valid option is to harvest the graft from the lateral lining of the tongue.

The relationship between erectile function and complex panurethral stricture: a preliminary investigative and descriptive study

The aim of this study was to evaluate erectile function in patients with panurethral stricture after urethral reconstruction. Totally, 65 patients were enrolled. Different urethral reconstructions were performed according to the details of urethral strictures. The erectile function was evaluated before and after surgery. The length and location of stricture and duration from initial diagnosis to operation were recorded. The International Index of Erectile Function-5 (IIEF-5) scores, the quality of life (QoL) scores and the maximal flow rate were obtained before and 3, 6, and 12 months after surgery. A significant improvement in QoL and maximal flow rate was observed 3, 6, and 12 months after surgery compared with those observed before surgery (P < 0.05). An impairment of erectile function was observed in patients with multi-site stricture 3 months after surgery (P < 0.05). Subsequently, these patients recovered 6 and 12 months after surgery. Three months after surgery, the IIEF-5 scores in patients with anterior urethral stricture were higher than those with multi-site stricture. Similar results were observed 6 and 12 months after surgery. No significant difference in age or duration from initial diagnosis to final operation was observed between patients with erectile dysfunction after surgery and patients with normal erectile function. However, a linear regressive relationship was detected between IIEF-5 scores and location of urethral stricture. Surgical reconstruction for treating panurethral strictures has limited effects on erectile function. The location of the stricture, particularly when extended to posterior urethra, was found to be associated with erectile function after surgery.

A Rationale for Procedure Selection to Repair Female Urethral Stricture Associated with Urethrovaginal Fistulas

PURPOSE We investigated a rationale for procedure selection to repair female urethral stricture associated with urethrovaginal fistula. We compared the outcomes of the 5 techniques used. MATERIALS AND METHODS Between January 1999 and October 2011, 44 female patients with urethral stricture associated with urethrovaginal fistula were treated using a total of 5 techniques. The surgical techniques were labial pedicle flap urethroplasty in 24 patients, vulvar flap urethroplasty in 3, anterior vaginal flap urethroplasty in 11, end-to-end anastomosis in 4 and bladder flap urethroplasty in 2. Supplementary procedures were performed in some patients during urethroplasty, including bladder neck reshaping for incontinence in 5, intestinal-vaginal fistula repair in 3, colpoplasty for island vulvar skin flaps in 3, middle vaginal stricture vaginoplasty in 2 and enlargement of the vaginal introitus in 1. RESULTS Average postoperative followup was 42.3 months (range 6 to 140). Urethrovaginal fistula recurred in 2 patients because of infection, urethral stricture developed in 1 and stress incontinence appeared in 1. The other patients voided normally with an average maximum urine flow greater than 15 ml per second (range 16.7 to 46). The overall anatomical success rate was 93.18% (41 of 44 cases) and the functional success rate was 90.91% (40 of 44). CONCLUSIONS Surgical procedures for treating female urethral strictures with urethrovaginal fistulas should be based on fistula location, stricture length and vaginal anatomy. A transvaginal approach might be optimal if the vagina is wide and easily dilated. Pedicle labial flap urethroplasty was a reliable technique for complex strictures.

Squamous Cell Carcinoma of the Bulbar Urethra Accompanied by Lichen Sclerosus: A Case Report:

Squamous cell carcinoma (SCC) of the bulbar urethra accompanied by lichen sclerosus (LS) is rarely reported. This study reports the case of a 56-year-old man with urethral squamous cell carcinoma (USCC) accompanied by a long history of genital LS. The man presented with a painful perineal mass and had a long-term history of urethral strictures and urethral dilatation. The patient developed a periurethral abscess that expanded to the perineum and formed an urethrocutaneousperineal fistula. An organ-sparing perineal resection and fistulectomy was performed according to the patient’s wishes. During the operation, residue-like pus mixed with necrotic tissues drained out. A section of the prepuce and the necrotic tissues were sent for histological analysis. Hematoxylin and eosin (HE) staining of the excised prepuce revealed classical LS. HE and immunohistochemical (IHC) staining of the necrotic tissues showed well-differentiated USCC. IHC staining showed the USCC to be positive for P53 and Ki-67 and negative for P16, suggesting the USCC was probably associated with LS. The patient received high-dose chemotherapy and radiation therapy and died 10 months after surgery.

Intermediate-Term Outcomes and Complications of Long Segment Urethroplasty with Lingual Mucosa Grafts

Purpose: We evaluated outcomes and donor site complications in male patients with complex urethral strictures who underwent urethroplasty using with long strip oral mucosal grafts. We also analyzed whether a lingual mucosa graft is a good substitute for repairing long segment urethral strictures. Materials and Methods: This retrospective study was done in 81 male patients with complex urethral strictures who underwent oral mucosal graft urethroplasty. Patients with long segment (8 cm or greater) anterior urethral strictures who were considered candidates for long strip lingual mucosa graft urethroplasty were included in study. Results: Oral mucosal graft urethroplasty was performed in 81 patients with complex urethral strictures between August 2006 and December 2014. Mean urethral stricture length was 12.1 cm (range 8 to 20). A single 9 to 12 cm long strip lingual mucosa graft was used in 52 patients, a lingual mucosa graft greater than 12 cm was placed in 17 and a lingual mucosa graft combined with a buccal mucosal graft was used in 12. Mean followup was 41 months (range 15 to 86) postoperatively. The overall urethroplasty success rate was 82.7%. Urethral complications developed in 14 patients (17.3%), including urethral strictures in 10 and urethrocutaneous fistulas in 4. At 12 months 5 patients (6.2%) reported minimal difficulty with fine motor movement of the tongue. Conclusions: Lingual mucosa harvested from the ventrolateral surface of the tongue can provide a wide and long graft that is an excellent urethral substitute. Donor site complications are primarily limited to postoperative year 1. Our study confirms that the lingual mucosa graft is a good substitute for urethral reconstruction and lingual mucosa graft urethroplasty is a valuable procedure to treat long anterior urethral strictures.