Long-term Outcomes of Tension-free Vaginal Tape Procedure for Treatment of Female Stress Urinary Incontinence with Intrinsic Sphincter Deficiency.

PURPOSE: To assess the long-term outcomes of tension-free vaginal tape (TVT) for stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD) and to identify influencing factors for failure in these cases. METHODS: A total of 136 women who underwent TVT procedures with minimum follow-up duration of 3 years were included in the study. Patients were divided into two groups (non-ISD and ISD groups) based on preoperative urodynamic studies. Patient outcomes were assessed from retrospective chart review and telephone research. Cure was defined as the subjective resolution of SUI in any circumstances. Improvement was defined as the subjective improvement of SUI without complete resolution. Failure was defined as the subjective lack of improvement of SUI. Patients in ISD group were subdivided into two subgroups (cure and non-cure groups) and were compared to identify influencing factors for TVT procedure failure. RESULTS: Eighty-nine patients were in non-ISD group, and 47 in ISD group. The mean follow-up durations were 50.3±9.2 and 49.7±9.7 months, respectively. Subjective cure rate was 75.3% for non-ISD group, and 76.7% for ISD group (P>0.05). Improvement rate was 6.7% for non-ISD group, and 2.1% for ISD group (P>0.05). Satisfaction scores was 3.8±1.2 points in the non-ISD group, and 3.5±1.2 points in ISD group (P>0.05). In ISD subgroups, VLPP was 41.9±12.0 cmH(2)O for non-cure group, and 50.5±8.6 cmH(2)O for cure group, and was the only factor that showed significant statistical difference between the two subgroups (P=0.011). CONCLUSIONS: With our long-term results, TVT is an effective treatment even in women with ISD. However, ISD patients with low VLPP should be counseled carefully about TVT outcome.

Down-regulation of p57Kip2 induces prostate cancer in the mouse.

p57(Kip2) has been considered a candidate tumor suppressor gene because of its location in the genome, biochemical activities, and imprinting status. However, little is known about the role of p57(Kip2) in tumorigenesis and cancer progression. Here, we show that the expression of p57(Kip2) is significantly decreased in human prostate cancer, and the overexpression of p57(Kip2) in prostate cancer cells significantly suppressed cell proliferation and reduced invasive ability. In addition, overexpression of p57(Kip2) in LNCaP cells inhibited tumor formation in nude mice, resulting in well-differentiated squamous tumors rather than adenocarcinoma. Furthermore, the prostates of p57(Kip2) knockout mice developed prostatic intraepithelial neoplasia and adenocarcinoma. Remarkably, this mouse prostate cancer is pathologically identical to human prostate adenocarcinoma. Therefore, these results strongly suggest that p57(Kip2) is an important gene in prostate cancer tumorigenesis, and the p57(Kip2) pathway may be a potential target for prostate cancer prevention and therapy.

The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth.

Typically, the initial response of a prostate cancer patient to androgen ablation therapy is regression of the disease. However, the tumor will progress to an "androgen-independent" stage that results in renewed growth and spread of the cancer. Both nuclear factor-kappaB (NF-kappaB) expression and neuroendocrine differentiation predict poor prognosis, but their precise contribution to prostate cancer progression is unknown. This report shows that secretory proteins from neuroendocrine cells will activate the NF-kappaB pathway in LNCaP cells, resulting in increased levels of active androgen receptor (AR). By blocking NF-kappaB signaling in vitro, AR activation is inhibited. In addition, the continuous activation of NF-kappaB signaling in vivo by the absence of the IkappaBalpha inhibitor prevents regression of the prostate after castration by sustaining high levels of nuclear AR and maintaining differentiated function and continued proliferation of the epithelium. Furthermore, the NF-kappaB pathway was activated in the ARR(2)PB-myc-PAI (Hi-myc) mouse prostate by cross-breeding into a IkappaBalpha(+/-) haploid insufficient line. After castration, the mouse prostate cancer continued to proliferate. These results indicate that activation of NF-kappaB is sufficient to maintain androgen-independent growth of prostate and prostate cancer by regulating AR action. Thus, the NF-kappaB pathway may be a potential target for therapy against androgen-independent prostate cancer.