René Yiou

Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual.

Introduction Intracavernous alprostadil injection (IAI) is a widely used treatment for sexual rehabilitation (SR) after radical prostatectomy (RP). It is unknown whether the continuation of IAI beyond 1 year continues to improve erectile function. Aims To assess evolution of sexual function in patients using IAI who are nonresponsive to phosphodiesterase type 5 inhibitors (PDE5i) between 12 (M12) and 24 (M24) months after RP. Methods We retrospectively studied 75 men with a nerve-sparing laparoscopic RP, who had normal preoperative erectile function, and who regularly used IAI for SR for at least 24 months. At M12, no patients had responded to PDE5i. Main Outcome Measures At 12 and 24 months, sexual function was assessed with the UCLA Prostate Cancer Index (UCLA-PCI), International Index of Erectile Function (IIEF)-15, and erection hardness score (EHS) with and without IAI. We also assessed the satisfaction rate with IAI, injection-related penile pain, and satisfaction of treatment. Statistical analysis was performed by using t-tests for paired data and Spearman's rho correlation coefficients to assess the relationships between scores at M12 and M24. Results Improvement of nocturnal erection was noted (UCLA-PCI, question 25); however, no significant difference was found for IIEF-erectile function with (19.60 ± 9.80 vs. 18.07 ± 10.44) and without IAI (4.63 ± 2.93 vs. 4.92 ± 4.15), UCLA-PCI-sexual bother (37.14 ± 21.45 vs. 37.54 ± 19.67), nor the EHS score with (2.97 ± 1.30 vs. 2.57 ± 1.30) and without IAI (0.67 ± 1.11 vs. 0.76 ± 0.10). The rate of satisfaction with treatment decreased over time (66.6% vs. 46.7%, P = 0.013). Improved response to IAI at M12 was not correlated to improvement in spontaneous erections at M24. Conclusion The response to IAI remained stable after 2 years of treatment, and no significant improvement of spontaneous erections during intercourse attempts was found between M12 and M24. Patients should be informed of the limited effect of IAI on natural erections after 1 year. Yiou R, Bütow Z, Parisot J, Binhas M, Lingombet O, Augustin D, de la Taille A, and Audureau E. Is it worth continuing sexual rehabilitation after radical prostatectomy with intracavernous injection of alprostadil for more than 1 year? Sex Med 2015;3:42–48.

Aims: To update the 2‐year outcomes of the TOMS™ transobturator male sling for treating post‐prostatectomy urinary incontinence (pRP‐UI) in a group of patients previously evaluated at 1 year.Methods: We prospectively followed 40 patients with pRP‐UI before and 6, 12, and 24 months after implantation of the TOMS™ transobturator male sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA‐PCI (urinary bother domain), PGI‐I, and daily pad use. Success was defined as patients wearing no or only one security pad. We also report on any other surgical procedures for treating persistent incontinence during the follow‐up period.Results: Of 40 patients included in the 1‐year follow‐up, seven required additional surgical treatment. In the remaining patients (n = 33), significant improvement (P < 0.001) compared to baseline was seen, and a subsequent tendency (non‐significant) toward impairment was noted throughout the three postoperative follow‐ups for the ICIQ (14.4 ± 4.4 [baseline], 7.6 ± 5.7 [6 months], 8.1 ± 5.6 [12 months], 8.9 ± 5.5 [24 months]), USP‐stress urinary (6.7 ± 2.2, 2.8 ± 2.4, 2.8 ± 2.4, 3.2 ± 2.8), ULCA‐PCI‐urinary bother (10.0 ± 12.5, 66.0 ± 33.0, 64.0 ± 31.5, 62.0 ± 30.7) scores, and pad use (2.5 ± 1.2, 0.7 ± 1.1, 0.8 ± 1.2, 0.9 ± 1.2). Significant impairment in postoperative PGI‐I (6.2 ± 0.9, 6.1 ± 0.9, 5.8 ± 1.1, P = 0.028) and USP‐overactive bladder symptoms scores (5.4 ± 3.6 [6 months] vs. 6.6 ± 3.7 [24 months], P = 0.046) were noted. A total of 18 (54.5%), 17 (51.5%), and 15 (45.5%) patients wore no postoperative pad, respectively.Conclusion: Approximately half of the patients continue to wear no pad 2 years after TOMS™ transobturator male sling implantation. However, a tendency toward impaired continence, possibly associated with overactive bladder symptoms, was noted. Neurourol. Urodynam. 35:44–47, 2016.

Introduction: Erectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested.Aim: This study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections.Methods: This is a 1-year follow-up cohort study of 75 patients treated by RP for localized prostate cancer in a urology department setting between January 2007 and December 2008. Data were prospectively collected at 6 and 12 months post-RP.Main Outcome Measures: The EHS, the International Index of Erectile Function (IIEF) reference questionnaire, the Global Assessment Questionnaire (GAQ), and Numeric Pain Scale (NPS) were collected. Convergent validity (Spearman correlation coefficients with IIEF domains), known-groups validity (comparing EHS scores across ED severity groups), time and treatment responsiveness (effect size with/without treatment and over the follow-up period), and predictive ability (area under the receiver operating characteristics curve [AUC-ROC]) were analyzed for this study.Results: The EHS showed good convergent validity (all Spearman coefficients significant at the P < 0.05 level), adequate known-groups validity (global differentiation between IIEF-EF severity groups; P < 0.001), and treatment responsiveness (effect size: +1.8 [6 months], +2.1 [12 months]), but limited time responsiveness and predictive ability of the EHS for a normal EF at 12 months follow-up when compared with the IIEF-EF domain (AUC-ROC: 0.72 vs. 0.85; P < 0.01).Conclusion: Our findings support the overall good psychometric properties of the EHS in patients with post-RP ED treated with alprostadil injections. However, evidence for limited predictive validity and responsiveness to change over time should be considered for its use in clinical follow-up in this population.

Aims To evaluate pain and embarrassment associated with invasive urodynamics and to determine underlying factors. Methods One hundred seventy one consecutive patients referred to our department for invasive urodynamics were evaluated using visual numeric rating scales for sensations of apprehension, pain, and embarrassment during several steps of the procedure (scores ranging from 0 [no symptom] to 10 [worst imaginable symptom]). We also investigated the influence of sex, age, information provided before urodynamics, and medical indication on these sensations. The Spearman correlation, non‐parametric test, and logistic regression analysis were performed to determine explicative factors for the most painful sensations. Results The mean age was 61.0 (standard deviation ± 15 years). The mean (95% confidence interval [CI]) apprehension level was 2.9/10 (2.4; 3.4). The mean (95% CI) pain levels at installation on urodynamic table, transurethral catheter insertion (cystometry), and catheter repositioning (urethral pressure profilometry) were 0.3/10 (0.1; 0.5), 1.9/10 (1.6; 2.3), and 1.3/10 (1.0; 1.7), respectively. At catheter insertion, 25% of patients reported a pain level ≥4/10. The mean embarrassment level due to urination in front of the doctor was 1.9/10 (1.4; 2.3). Painful sensations reported during the different steps were strongly correlated with each other and with levels of apprehension and embarrassment. Age Neurourol. Urodynam.

Aims To evaluate stress urinary incontinence (SUI), overactive bladder (OAB), and obstructive symptoms in patients with post-radical prostatectomy urinary incontinence (pRP-UI) treated with the bulbar compressive sling TOMS, and investigate the effect of each urinary symptom on urinary bother. Materials and Methods We prospectively followed 40 patients with pRP-UI before, and 6 and 12 months (T6 and T12, respectively) after implantation of the TOMS sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA-PCI (urinary bother domain), PGI-I, and daily pad use. Success was defined as patients wearing no pads or using one security pad. Results Significant improvement of mean USP-SUI (6.97/9, 3.35, 3.02, P < 0.001) and USP-OAB domains (8.1/21, 5.74, 5.71, P < 0.001), ICIQ (15.15/21, 8.17/21, 8.35/21, P < 0.01), urinary bother (92.5/100, 42.5, 41.87, P < 0.001), and pad number (2.78, 1.01, 1.03, P < 0.001) were noted between baseline, T6, and T12. At baseline, 32 (80%) patients reported urge incontinence. Urinary bother strongly correlated with UPS-SUI but not with UPS-OAB score. At T12, 22 (55%) patients with pad use were considered cured, and 13 (32.5%) patients reported a greatly improved urinary tract condition (PGI-I). Improvement of USP-SUI and USP-OAB scores correlated with improvement of ICIQ and PGI scores. The USP-obstructive domain remained unchanged. Conclusion The TOMS sling improves SUI and OAB symptoms without generating obstructive symptoms. OAB symptoms including urge incontinence reported by most patients were not a major concern at baseline; however, improvement of these symptoms was associated with improvement of continence and PGI-I scores. Neurourol. Urodynam. 34:12–17, 2015.

Introduction The effects of intracavernous alprostadil injection (IAI), a primary treatment for post‐radical prostatectomy (RP) erectile dysfunction (ED) (pRPED), on the sex life of women partnered with men who have undergone RP have received little attention. Aims The aim of this study is to investigate the sexual quality of life in female partners of men receiving IAIs for pRPED. Methods We retrospectively studied the sex lives of 152 women partnered with men who were being treated for pRPED with IAI and previously had normal erectile function. Women completed the Index of Sexual Life (ISL) questionnaire 1 year after their partner's RP. Male patients completed the International Index of Erectile Function (IIEF‐15), the Erection Hardness Score (EHS) questionnaire, the International Consultation on Incontinence Questionnaire (ICIQ), and the UCLA Prostate Cancer Index (UCLA‐PCI) urinary function questionnaire. Penile pain was assessed using the visual analog scale (VAS). Statistical analysis was performed using t‐tests, Spearman correlation, and multiple linear regression. Main Outcome Measures Female sexual life satisfaction (SLS), sexual drive (SD), and general life satisfaction (GLS) were assessed using the ISL questionnaire. Results Mean ages for the 104 couples included were 62.3 and 59.8 years for the men and women, respectively. Mean ISL, SD, SLS, and GLS scores at 12 months were 25.4, 3.8, 14.1, and 7.5, respectively. ISL scores were strongly correlated with IIEF‐15 domains, mainly erectile function (r > 0.41, P < 0.00002) and intercourse satisfaction (r > 0.27, P < 0.005). Age and VAS, ICIQ, and UCLA‐PCI scores were negatively correlated with some ISL domains. IIEF‐15 erectile function and intercourse satisfaction were the most significant domains predicting female SLS. An IIEF‐15 erectile function of 25 corresponded to a 75% chance of an SLS score ≥18. Conclusion Indexes of female sexual quality of life were low overall but were highly correlated with the partner's response level to IAI treatment. IAI‐related pain, increased age, and poor urinary function of the male partner appear to negatively impact female sex life.

What's known on the subject? and What does the study add?: Cell therapy using muscle precursor cell ( MPC ) injections has shown promise for urinary incontinence due to intrinsic sphincter deficiency ( ISD ), but the cell‐preparation process is complex and costly. Implantation of freshly isolated myofibres carrying MPCs , mainly satellite cells, was very efficient in repairing muscle damage in recent animal experiments. In a phase I clinical trial, we investigated whether periurethral myofibre implantation generated local myogenesis and improved continence in 10 patients (five men and five women) with ISD . We found that myofibre implantation increased intraurethral pressure and periurethral electromyographic activity in patients with ISD . There were no serious side‐effects. Objectives: To assess the safety of periurethral myofibre implantation in patients with urinary incontinence due to intrinsic sphincter deficiency ( ISD ) To assess the resulting myogenic process and effects on urinary continence. Patients and Methods: An open‐label non‐randomised phase I clinical trial was conducted in five men and five women with ISD (mean age, 62.5 years). A free muscle strip from the patient's gracilis muscle was implanted around the urethra as a means to deliver locally myofibres and muscle precursor cells ( MPCs ). Patients were assessed for collection formation and incomplete bladder emptying. The maximum urethral closure pressure ( MUCP ) and concomitant periurethral electromyographic ( EMG ) activity were recorded before surgery and 1 and 3 months after surgery. Continence was assessed using the 24‐h pad test and self‐completed questionnaires, for 12 months. Results: There were no serious side‐effects. Continence improved significantly during the 12‐month follow‐up in four of the five women, including two who recovered normal continence. In the women, MUCP increased two‐fold and de novo EMG periurethral activity was recorded. In the men, MUCP and EMG recordings showed similar improvements but the effect on continence was moderate. The few patients enrolled could affect these results. Conclusions: This is the first report of a one‐step procedure for transferring autologous MPCs via myofibre implantation in patients with ISD . EMG and urodynamic assessments showed improvement of periurethral muscle activity. Further work is needed to confirm and improve the therapeutic efficiency of this procedure.