Prospective comparison of one year follow-up outcomes for the open complete intrafascial retropubic versus interfascial nerve-sparing radical prostatectomy.

Current work provides a prospective direct comparison between Open complete intrafascial-radical-prostatectomy (OIF-RP) and interfascial-RP in all outcomes in single centre series. Both techniques were done prospectively in 430 patients. Inclusion criteria for OIF-RP (n=241 patients) were biopsy Gleason-score ≤6 and PSA ≤10 ng/ml while for interfascial-RP (n=189) were Gleason-score ≤7 and PSA ≤15. The perioperative parameters (e.g. operative time, complications etc.), pathologic results, surgical margins and revisions were reviewed. Pre- and postoperative (3 and 12 months) evaluation of continence and potency was performed. All patients have preoperative IIEF-score of ≥15. Continence was classified as complete (no pads), mild (1-2 pads/day) and incontinence (>2 pads/day). Median patients' age was 63.7 vs. 64.5 years for OIF-RP vs. Interfascial-RP, respectively. Preoperative PSA-level was significantly lower in OIF-RP (5.8 vs. 7.1), otherwise, similar perioperative data in both groups except for more frequent pT3-tumors in interfascial-RP group (18%). No statistical significance regarding continence was observed between OIF-RP vs. Interfascial-RP groups at 3 (82% vs. 85%) and 12 months (98% vs. 96%) postoperatively. Potency rates (IIEF ≥15) after OIF-RP were 96% (≤55 years), 72% (55-65), and 75% (>65 years) at 12 months. The respective rates for interfascial-group were 58%, 61% and 51%. There was an advantage for OIF-RP potency-outcomes without significance over Interfascial-RP in weak potency patients (IIEF=15-18). We conclude that OIF-RP is associated with better functional results without compromising early oncological results compared to interfascial-RP. Complete preservation of periprostatic fasciae provides significantly better postoperative recovery of sexual function even for weak potency patients. Longer follow-up is mandatory to further evaluate the outcome results of this technique

Concentration-dependent alpha(1)-Adrenoceptor Antagonism and Inhibition of Neurogenic Smooth Muscle Contraction by Mirabegron in the Human Prostate

Introduction: Mirabegron is available for treatment of storage symptoms in overactive bladder, which may be improved by β3-adrenoceptor-induced bladder smooth muscle relaxation. In addition to storage symptoms, lower urinary tract symptoms in men include obstructive symptoms attributed to benign prostatic hyperplasia, caused by increased prostate smooth muscle tone and prostate enlargement. In contrast to the bladder and storage symptoms, effects of mirabegron on prostate smooth muscle contraction and obstructive symptoms are poorly understood. Evidence from non-human smooth muscle suggested antagonism of α1-adrenoceptors as an important off-target effect of mirabegron. As α1-adrenergic contraction is crucial in pathophysiology and medical treatment of obstructive symptoms, we here examined effects of mirabegron on contractions of human prostate tissues and on proliferation of prostate stromal cells. Methods: Contractions were induced in an organ bath. Effects of mirabegron on proliferation, viability, and cAMP levels in cultured stromal cells were examined by EdU assays, CCK-8 assays and enzyme-linked immunosorbent assay. Results: Mirabegron in concentrations of 5 and 10 μM, but not 1 µM inhibited electric field stimulation-induced contractions of human prostate tissues. Mirabegron in concentrations of 5 and 10 µM shifted concentration response curves for noradrenaline-, methoxamine- and phenylephrine-induced contractions to the right, including recovery of contractions at high concentrations of α1-adrenergic agonists, increased EC50 values, but unchanged Emax values. Rightshifts of noradrenaline concentration response curves and inhibition of EFS-induced contractions were resistant to L-748,337, l-NAME, and BPIPP. 1 µM mirabegron was without effect on α1-adrenergic contractions. Endothelin-1- and U46619-induced contractions were not affected or only inhibited to neglectable extent. Effects of mirabegron (0.5–10 µM) on proliferation and viability of stromal cells were neglectable or small, reaching maximum decreases of 8% in proliferation assays and 17% in viability assays. Mirabegron did not induce detectable increases of cAMP levels in cultured stromal cells. Conclusion: Mirabegron inhibits neurogenic and α1-adrenergic human prostate smooth muscle contractions. This inhibition may be based on antagonism of α1-adrenoceptors by mirabegron, and does not include activation of β3-adrenoceptors and requires concentrations ranging 50-100fold higher than plasma concentrations reported from normal dosing. Non-adrenergic contractions and proliferation of prostate stromal cells are not inhibited by mirabegron

Patients' perception of surgical outcomes and quality of life after retroperitoneoscopic and open pyeloplasty

PURPOSE To report postoperative health-related quality of life (HRQoL) and patients' subjective evaluations of open pyeloplasty (OP) and retroperitoneoscopic pyeloplasty (RP) and influences on preoperative counselling. METHODS 107 patients (age 16-80 years, mean 31.5) with symptomatic primary ureteropelvic junction obstruction who underwent OP (32) or RP (75) were evaluated prospectively. HRQoL was evaluated using Short Form 36 (SF-36) questionnaires with 1 year follow-up. Operative outcomes were evaluated using a self-designed questionnaire regarding cosmetic outcomes, objective postoperative/current pain, convalescence and return to work. RESULTS The mean operative time was 174.4 vs. 161.4 min for RP versus OP, respectively, without intraoperative complications/conversions. There was an advantage for RP--except for two domains--without significance in any of the eight SF-36 domain scores. An advantage favouring RP in all aspects of the second questionnaire with significance in four aspects (cosmetic results, scar length, pain and convalescence) was found. Five weeks postoperatively, 58.7% (RP) vs. 25.8% (OP) were fully convalescent compared to 87.0% (RP) vs. 71.0% (OP) at 8 weeks. Similarly, 58.7 vs. 45.1% returned work 5 weeks postoperatively while 93.5 vs. 74.2% did so after 8 weeks, respectively. The small sample size, more questions on satisfaction/regret and mixed design are the main study limitations. CONCLUSION RP provides the same functional results beside earlier convalescence, better HRQoL and patients' convenience with surgery, which favours its inclusion in preoperative counselling providing patients with realistic postoperative expectations

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

Introduction: Lower urinary tract symptoms (LUTS) due to overactive bladder (OAB) are caused by spontaneous detrusor contractions. Medical treatment with muscarinic receptor antagonists or β3-adrenoceptor agonists aims to inhibit detrusor contractions, but overall results are unsatisfactory. Consequently, improved understanding of bladder smooth muscle contraction and identification of novel compounds for its inhibition are needed to develop alternative options. A role of the GTPase Rac1 for smooth muscle contraction has been reported from the prostate, but is unknown in the human detrusor. Here, we examined effects of the Rac inhibitors NSC23766, which may also antagonize muscarinic receptors, and EHT1864 on contraction of human detrusor tissues. Methods: Female and male human detrusor tissues were obtained from radical cystectomy. Effects of NSC23766 (100 µM) and EHT1864 (100 µM) on detrusor contractions were studied in an organ bath. Results: Electric field stimulation induced frequency-dependent contractions of detrusor tissues, which were inhibited by NSC23766 and EHT1864. Carbachol induced concentration-dependent contractions. Concentration response curves for carbachol were shifted to the right by NSC23766, reflected by increased EC50 values, but unchanged Emax values. EHT1864 reduced carbachol-induced contractions, resulting in reduced Emax values for carbachol. The thromboxane analog U46619 induced concentration-dependent contractions, which remained unchanged by NSC23766, but were reduced by EHT1864. Conclusions: NSC23766 and EHT1864 inhibit female and male human detrusor contractions. NSC23766, but not EHT1864 competitively antagonizes muscarinic receptors. In addition to neurogenic and cholinergic contractions, EHT1864 inhibits thromboxane A2-induced detrusor contractions. The latter may be promising, as the origin of spontaneous detrusor contractions in OAB is noncholinergic. In vivo, both compounds may improve OAB-related LUTS

Ghrelin Aggravates Prostate Enlargement in Rats with Testosterone-Induced Benign Prostatic Hyperplasia, Stromal Cell Proliferation, and Smooth Muscle Contraction in Human Prostate Tissues

Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH

Impact of the 'Repositioning Test' on Postoperative Outcome of Retroluminar Transobturator Male Sling Implantation

OBJECTIVE: To evaluate prospectively the value of the ‘repositioning test’ (RT) in preoperative patient selection for the efficacy of male stress urinary incontinence (SUI) treatment using a retroluminar transobturator male sling (AdVance sling). PATIENTS AND METHODS: 65 consecutive patients with SUI after radical prostatectomy were included in this singlecenter prospective study. Preoperatively, patients were classified into those with ‘positive’ and ‘negative’ RT. Postoperative results were analyzed and the association between the result of the RT and postoperative outcome was evaluated. RESULTS: 53 patients (81.5%) showed preoperatively a positive RT and 12 patients (18.5%) a negative RT. After a followup of 12 months, patients with positive RT showed a cure rate (0 pads/day) of 83% and patients with a negative RT showed only a cure rate of 25%. A positive RT significantly correlated with cure in outcome (p < 0.001). CONCLUSIONS: Patients with positive RT have a significantly better hance for successful AdVance sling implantation. The RT is minimally invasive, easy to learn and easy to perform. Therefore, the RT is a very useful tool for preoperative patient selection

Sending Granny to Chiang Mai: debating global outsourcing of care for the elderly

This article ties in with existing discussions on global care chains, family separation and the devaluation of social-reproductive work. We explore the new trend of outsourcing care for the elderly to countries with lower wages. We base our analysis on the debate in the German press and supplement it with insights from ethnographic field observations in two care homes in Thailand. We identify a discourse of abandonment, which shows how outsourcing the care of the elderly unsettles the privilege of sedentarism that is often taken for granted in the Global North. Furthermore, the newspaper articles tend to villainize people who seek care for their loved ones abroad. We argue that both discourses foster a neoliberal rationale of individualized responsibility and obfuscate the deep systemic roots of the care crisis in the Global North. However, by extending the discussion on outsourcing care for the elderly beyond the dominant media discourses, we envisage a rich potential for provoking political debate on the revaluation of care