Long-term results of suprapubic bladder neck closure for treatment of the devastated outlet.

OBJECTIVES: To assess the long-term success of suprapubic bladder neck closure in patients with irreparably damaged bladder outlets. METHODS: A cohort of 35 patients with intractable urinary incontinence secondary to severe posterior urethral/bladder neck damage underwent suprapubic bladder neck closure. Patients were assessed with regard to the success of procedure, as well as early and late complications. RESULTS: With a mean follow-up of 79 months (range 12 to 164), suprapubic bladder neck closure was successful in 29 (83%) of 35 patients. One revision of the bladder neck improved the success rate to 94% (33 of 35). Early and late complications, excluding bladder neck fistula, were reported in 3 (9%) and 5 (14%) of 35 patients, respectively. CONCLUSIONS: High success and acceptable complication rates can be achieved with suprapubic bladder neck closure for the treatment of severe urinary incontinence secondary to a devastated bladder outlet.

Regulation of u-PA gene expression in human prostate cancer.

u-PA contributes to CaP progression, especially in the metastatic androgen-insensitive state. In vitro, u-PA is expressed by androgen-insensitive, but not androgen-sensitive, CaP cell lines. We hypothesized that in androgen-sensitive CaP an activated ARE represses u-PA expression but in androgen-insensitive CaP this repression is lost and u-PA is upregulated through MAP kinase signaling pathways. To determine whether binding of the DHT-AR complex to AREs in the u-PA promoter region represses u-PA transcription in androgen-sensitive CaP, we studied 2 PC3 androgen-insensitive human CaP cell lines stably transfected with AR [PC3(AR)(2) and PC3(AR)(13)] and 1 mock-transfected cell line [PC3(M)]. In the presence of the synthetic androgen mibolerone, both PC3(AR)(2) and PC3(AR)(13), but not PC3(M), cells showed decreased u-PA expression as assayed by Western and Northern blotting. The AR inhibitor flutamide abrogated mibolerone's effect. Androgen regulation of a second gene, PSA, was also demonstrated in the PC3(AR)(2) cell line. To explore the pathway stimulating u-PA expression in CaP, we performed transient transfections in PC3(AR)(2) cells using u-PA promoter-regulated CAT reporter constructs. Compared to full-length u-PA promoter-CAT constructs, either deletion or mutation of the 5' AP-1 or PEA3 site reduced CAT expression. The location of androgen responsiveness in the u-PA promoter was not identified through the combination of promoter search and transient transfection assays, indicating that a more complicated mechanism is involved in the AR-mediated downmodulation of u-PA expression.