Analysis of a large data set from multiple institutions shows that surgical removal of symptomatic large prostatic adenomas can be carried out with good outcomes by using robot-assisted laparoscopy.

Introduction Numerous clinical series have reported an association between 5-alpha-reductase inhibitors (5ARIs) and sexual dysfunction, but there are limited preclinical data available. Aim To further investigate the mechanisms of erectile dysfunction (ED) related to 5ARI therapy using a rat model. Main Outcome Measures Outcome measures include serum dihydrotestosterone (DHT), relaxant and contractile properties of cavernosal muscle, and nitric oxide synthase expression. Methods Twenty adult male Sprague-Dawley rats were randomized into control (N = 10) and dutasteride (0.5 mg/rat/day, in drinking water, N = 10) groups. Serum samples were obtained at baseline, from which DHT was measured after 30 days of treatment via radioimmunoassay (Beckman Coulter, Fullerton, CA, USA). Before the terminal blood draw, erectile response was measured using cavernosal nerve stimulation. The relaxant and contractile properties of cavernosal muscle strips were evaluated in tissue baths, and immunohistochemical (IHC) staining for nitric oxide synthase (NOS) and collagen deposition was performed. Results Mean serum DHT was suppressed by 86.5% (range 64.2–94.8%) after 30 days of 5ARI treatment and was statistically significant (P = 0.0024). In vivo erectile response in the dutasteride treated group decreased significantly compared with control (P < 0.001). While electrical field stimulation (EFS)-induced and acetylcholine-induced relaxation was decreased, EFS-induced and phenlyephrine-induced adrenergic contraction was significantly enhanced in the dutasteride group (P < 0.01). IHC studies demonstrated increased collagen deposition in the treatment arm as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS). Conclusions The 5ARIs, as demonstrated in these rat cavernosal smooth muscle studies, have a detrimental effect on erectile function. Enhanced iNOS expression may protect penile smooth muscle from fibrosis. The effect of 5ARIs on human sexual function warrants further investigation.

Introduction Benign prostatic hyperplasia (BPH) is a common problem affecting middle-aged and elderly men. First-line medical therapy includes α 1blockers and 5α-reductase inhibitors (5ARIs), such as finasteride and dutasteride. 5ARI use has been associated with adverse sexual outcomes, including erectile dysfunction (ED), ejaculatory dysfunction (EjD), and decreased libido. Aim To clarify the association between sexual adverse effects (AEs) and 5ARIs through review of literature concerning 5ARIs and to review the proposed mechanisms of these effects. Methods A comprehensive literature review, using MEDLINE and PUBMED search engines, was conducted for all publications concerning 5ARIs and sexual AEs. Main Outcome Measure Sexual adverse effects, such as ED, EjD, and decreased libido, were the measured outcomes of this literature review. Results Sexual AEs are reported in clinical trials at rates of 2.1% to 38%. The most common sexual AE is ED, followed by EjD and decreased libido. These effects occur early in therapy and attenuate over time. A proposed mechanism for sexual dysfunction involves decreased nitric oxide synthase activity due to decreased dihydrotestosterone. Conclusion The connection between 5ARIs and sexual dysfunction is apparent upon review of the literature. Though theories have been proposed, little is known about the exact mechanisms behind 5ARI-related sexual dysfunction. Since the connection between 5ARIs and sexual AEs is established in the literature, future research should be directed toward deciphering the pathophysiologic mechanisms. When more basic science knowledge is attained in this area, the focus can shift toward prevention and treatment.

gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTSThe erectile response was diminished in the HT group. Nitrergic and endotheliumdependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAMEtreated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONSSildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT. KEYWORDSrat, hypertension, L-NAME, erectile dysfunction, sildenafil Study Type -Aetiology (case control) Level of Evidence 3b OBJECTIVETo evaluate the effect of N(G)-nitro-Larginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODSThirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral

Objective: To elucidate the oncologic behavior of Micropapillary Urothelial Bladder Carcinoma (MPBC), a rare aggressive variant histology.Methods: All MPBC patients in SEER 17 database were compared with those with traditional urothelial carcinoma (UC). Kaplan-Meier curves were used to determine OS and CSS. A Cox proportional hazards model (CPH) was constructed to test the effect of covariates on outcomes.Results: From 2001-2008, 120 MPBC patients were identified, 0.1% of all bladder cancer. MPBC presented with more high grade (86.1% vs. 38.7%, p<0.0001) and more high stage disease (40.8% NMI vs. 90.4% NMI, p < 0.0001) than UC. Low grade (LG) NMI MPBC had worse OS and CSS compared to LG UC (p=0.0037, p<0.0001 respectively), and did no better than high grade (HG) NMI MPBC. No difference was detected between HG NMI MPBC and HG NMI UC pts. A CPH model controlling for stage, grade, treatment, age, race, and sex detected no significant survival difference in MPBC vs. UC (HR 1.04, p=0.7966). For NMI MPBC (n=49), only 4 patients underwent definitive therapy, of whom none died of disease. However, in those not receiving definitive therapy (n=45), 7 cancer specific deaths occurred (15.6%).Conclusion: Controlling for stage and grade, no survival difference could be detected between MPBC and UC. Low grade NMI MPBC behaved similarly to both high grade MPBC and high grade UC. We propose that all MPBC (regardless of grade) be managed as high grade disease, and that strong consideration for definitive therapy should be given in all cases.

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Subjects undergoing nephron sparing surgery undergo more posttreatment imaging compared to open radical nephrectomy. Although possibly associated with lower morbidity, thermal ablation is associated with significantly greater use of imaging compared to other small renal mass treatments. This may increase costs and radiation exposure, although further study is needed for confirmation.

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