Kim S, et al. World J Mens Health. 2021 Jan;39(1):48-64. https://doi.org/10.5534/wjmh.200007

We determined whether Rho-kinase inhibition would improve corporal veno-occlusive dysfunction by suppressing apoptosis and fibrosis via normalization of the Rho-kinase driven pathways related to the 2 structural alterations in a rat model of cavernous nerve crush injury. A total of 30 male 10-week-old male Sprague Dawley® rats were equally divided into 3 groups, including sham surgery, cavernous nerve crush injury and cavernous nerve crush injury treated with fasudil. The treated group received fasudil (30 mg/kg) daily for 4 weeks starting day 1 postoperatively. Electrostimulation and dynamic infusion cavernosometry were performed 4 weeks postoperatively. Penile tissue was processed for imm unohistochemistry, double immunofluorescent and Masson trichrome staining, TUNEL, caspase-3 activity assay and Western blot. The cavernous nerve crush injury group showed significantly lower intracavernous pressure/mean arterial pressure, and higher maintenance and drop rates than the sham surgery group. Rho-kinase inhibition in the injury plus fasudil group restored erectile responses and dynamic infusion cavernosometry parameters. Increased apoptosis, decreased immunohistochemical staining of α-SMA and increased caspase-3 activity were noted in the injury group. In that group densitometry revealed increased ROCK1 expression, increased MYPT1 phosphorylation, decreased Akt phosphorylation, decreased Bad phosphorylation and a decreased Bcl2-to-Bax ratio. A significantly decreased smooth muscle-to-collagen ratio and increased fibroblast pCofilin were also observed in the injury group, as was increased phosphorylation of cofilin, a downstream effector of LIMK2. Rho-kinase inhibition in the injury plus fasudil group alleviated the histological and molecular dysregulation. Our data suggest that early inhibition of Rho-kinase after cavernous nerve crush injury may prevent corporal apoptosis and fibrosis by suppressing the Akt/Bad/Bax/caspase-3 and LIMK2/cofilin pathways, preventing corporal veno-occlusive dysfunction and erectile dysfunction.

We evaluated the outcome at least 6 months after the tension-free vaginal tape or transobturator tape procedure in women with urinary incontinence, and identified factors predicting persistent stress urinary incontinence. A total of 464 women 28 to 80 years old (mean age 56) were included in the study. Tension-free vaginal tape (252) and transobturator tape (212) procedures were performed by the same surgeon. Mean followup was 10.8 months (range 6 to 52). Bladder perforations were noted in 12 patients (4.8%) in the tension-free vaginal tape group but there was no bladder perforation after the transobturator tape procedure (p = 0.001). The rate of urinary retention in the tension-free vaginal tape group was significantly higher than that in the transobturator tape group (15.1% vs 6.6%, p = 0.004). The overall cure rate was significantly higher in the tension-free vaginal tape group than in the transobturator tape group (92.1% vs 84.9%, p = 0.015). On multivariate analysis 4 variables were independent risk factors for persistent stress urinary incontinence, that is comorbid disease (OR 2.37, 95% CI 1.26-4.47, p = 0.008), urge urinary incontinence (OR 1.95, 95% CI 1.02-3.74, p = 0.044), severe grade of cystocele (OR 2.73, 95% CI 1.43-5.20, p = 0.002) and transobturator tape procedure (OR 2.87, 95% CI 1.50-5.47, p = 0.001). The cure rates in women with urinary incontinence are not similar after tension-free vaginal tape and transobturator tape procedures. Our findings suggest that characteristics including the type of procedure, comorbid diseases, mixed urinary incontinence and severe grade cystocele should be considered high risk factors for persistent stress urinary incontinence in these patients.