Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study.

UNLABELLED: Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials. PATIENT SUMMARY: We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results.

Polytetrafluoroethylene expanded prosthesis as replacement of the inferior vena cava in renal cell carcinoma with caval thrombus.

OBJECTIVE: To assess the outcomes of inferior vena cava replacement with polytetrafluoroethylene expanded prosthesis in patients with renal cell carcinoma and caval thrombosis. METHODS: All patients who underwent radical nephrectomy with inferior vena cava replacement by polytetrafluoroethylene expanded prosthesis for renal cancer associated with inferior vena cava thrombosis and a suspicion of inferior vena cava wall invasion from January 2000 to June 2011 were considered for this study. Demographic data, postoperative course, graft patency and survival data were evaluated. RESULTS: A total of 26 patients (median age 59.5 years, range 19.9-85.6 years) were included in the analysis. The median tumor diameter was 10 cm (range 5-14 cm). Histological invasion of the wall of the inferior vena cava was found in 16 (61.5%) cases. The median follow up was 28 months (range 1-136). A graft thrombosis occurred in five (19.2%) patients within the first year. Four of these patients died before the end of the second year. Patency of the inferior vena cava graft at 6 and 12 months was 88% and 79%, respectively. Overall survival probability at 3 years was 64%. CONCLUSION: Prosthetic replacement of the inferior vena cava can be carried out when invasion of the wall of the inferior vena cava is suspected. The postoperative complication rate in this subset of high-risk patients undergoing radical nephrectomy seems acceptable, and the patency of the prostheses is good in most of the cases.

Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage.

INTRODUCTION: Animal models of urinary incontinence and erectile dysfunction following radical prostatectomy (RP) are lacking. AIMS: To develop an animal model of combined post-RP urethral sphincter and erectile dysfunctions, and noninvasive methods to assess erectile function (EF) and urinary sphincter function (USF) during prolonged follow-up. METHODS: In the main experiments, 60 male Sprague Dawley rats were randomized to a sham operation (N = 30) or electrocautery of both sides of the striated urethral sphincter (N = 30). EF and USF were evaluated preoperatively and on postoperative days 7, 15, 30, 60, and 90. Sphincter and penile tissue samples were evaluated histologically on days 7 (N = 10) and 30 (N = 10) to detect apoptosis (TUNEL assays) and fibrosis (Trichrome Masson staining). MAIN OUTCOME MEASURES: To assess EF, we measured systemic and penile blood flow using penile laser Doppler and penile rigidity using a durometer before and after apomorphine injection. USF was assessed based on the retrograde leak point pressure (LPPr). RESULTS: Apomorphine increased baseline Doppler flow by 180% (95% confidence interval, 156-202%) and penile hardness from 3.49 ± 0.5 to 7.16 ± 0.82 Shore A units but did not change systemic arterial flow. Mean LPPr was 76.8 ± 6.18 mm Hg at baseline and decreased by 50% after injury, with no response to apomorphine on day 7. EF and USF impairments persisted up to 90 days post injury. Histology showed penile apoptosis on day 7 and extensive urethral sphincter and penile fibrosis on day 30. Our data did not allow us to determine whether the impairment in erectile response to apomorphine preponderantly reflected arterial penile insufficiency or veno-occlusive dysfunction. CONCLUSION: Electrocautery of the striated urethral sphincter caused severe and lasting impairment of EF and USF that could be monitored repeatedly using minimally invasive methods. This new animal model may hold potential for developing new treatments designed to correct post-RP impairments.