[Do phosphodiesterase type 5 inhibitors generics enhance discontinuation due to price with patients suffering from erectile dysfunction?] / Les génériques d'inhibiteur de la 5 phosphodiestérase améliorent-ils l'observance au traitement en raison d'un coût moindre ?

INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment of erectile dyfunction (ED). Cost of PDE5i is not covered by health insurance company in France. Few studies have examined the potential impact of the introduction of generic products of PDE5i on price non-compliance. The aim of the study was to compare the non-compliance rate because of price among patients treated for DE with generics of PDE5i and those treated with brand-name medications. METHOD: A multi-centre, cross-sectional, study that analyzed the answers to a questionnaire distributed to consultations in four hospitals for a period of twenty-eight months. Patients were included if they had DE treated for at least 3 months. The proportions between the two groups were compared with a non-inferiority test Wilcoxon-Mann-Whitney. RESULTS: One hundred and seventy-seven questionnaires were analyzed. Patients treated with generic PDE5i were significantly (α<0.05) as non-compliant because of price as patients treated with treated with brand-name PDE5i, respectively 34% (28/82) and 38% (36/95). The main causes of non-compliance were: high treatment costs, a lower than expected effect, lack of opportunity or sexual desire. The proportion of patients splitting the PDE5i tablet to achieve savings was 19% (33/177). To find the lowest price, 57% (101/177) of patients had consulted several pharmacies. These patients consulted 2.4±1.5 pharmacies. In the study population, 44% (78/177) of patients compared prices on commercial websites on the Internet. CONCLUSION: Patients treated with generic PDE5i are as unobservant as those treated with brand-name PDE5i. LEVEL OF EVIDENCE: 3.

[Robotic-assisted laparoscopic living donor nephrectomy: Study in donors and recipients from 155 cases]. / Néphrectomie laparoscopique assistée par robot dans le cadre du donneur-vivant : étude chez les donneurs et les receveurs à partir de 155 cas.

AIM: To evaluate morbidity and renal function of the donor and recipient during a robotic-assisted laparoscopic nephrectomy procedure. PATIENTS AND METHODS: It is a retrospective study of 155 consecutive patients by robot-assisted laparoscopy in the living donor. Mean operating time, warm ischemia time, blood loss, complications according to the Clavien classification and evolution of creatinine clearance were analyzed in the donors. Recovery of graft function, complications and changes in creatinine clearance were observed in recipients. RESULTS: The mean operating time was 176 (±23) minutes. The mean warm ischemia time was 4.8 (±0.6) minutes. Twenty seven complications were noted. The loss of renal function was 19% at 5 years in donors. Renal recovery was immediate for 153 recipients. Two were delayed due to sepsis. Two patients lost their graft at 15 and 18 months. Seventeen complications have been identified. The mean kidney function of the recipients is measured at 63ml/min at 5 years. CONCLUSION: Robotic-assisted laparoscopic nephrectomy procedure appears to provide the donor with low morbidity and a moderate decrease in creatinine clearance at 19% at 5 years. Morbidity is also low in recipients with very satisfactory 5-year mean renal function. The technique should promote donation. LEVEL OF EVIDENCE: 4.

[Treatment by stem cell therapy of erectile dysfunction of diabetic origin: State of the art]. / Traitement par les cellules souches de la dysfonction érectile d'origine diabétique : état des lieux.

PURPOSE: Review of various publications on stem cell therapy to treat erectile dysfunction of diabetic origin. MATERIAL AND METHODS: Bibliographic search in PUBMED performed using the keywords cell therapy strain/erectile dysfunction associated with diabetes. Among the 51 articles obtained from the PUBMED research, we selected 16 articles for their specificity of studying erectile dysfunction (DE) related to diabetes. RESULTS: Different types of stem cells have been studied: adipose derived mesenchymal stem cells/bone marrow derived mesenchymal stem cells as well as progenitor endothelial cells. The experimental protocols are quite similar from one study to the next with nevertheless some specifications concerning the studied cells and the monitoring of the latter. Intracavernous pressure (ICP) measured after the injection of stem cells into the corpus cavernosum was always significantly higher than the control populations. The addition of certain growth factors to stem cells by gene transfection improve the efficacy of the cells. No ideal tracking markers of the cells have been identified. CONCLUSION: The positive effect of the injection of stem cells on the ICP belongs to the cellular trans-differentiation effect but especially to the paracrine effects which have not yet been completely elucidated.

Mid term functional results following surgical treatment of recto-urinary fistulas postprostate cancer treatment.

INTRODUCTION: To evaluate the mid term functional results of patients treated for RUF and to determine an optimal treatment strategy to improve their quality of life. Recto-urinary Fistula (RUF) is a rare complication following prostate cancer treatment, and can have a major impact on patients' quality of life. There is a lack of consensus concerning the best approach and different techniques have been proposed: endoscopic, transrectal, perineal and transperitoneal (open, laparoscopic or robotic). MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who underwent RUF repair from January 2001 to December 2010 at our Institute. 16 patients who developed RUF following prostate cancer treatment were included in the study. The fistula had to be confirmed both clinically and by imaging. All patients had follow up consultation every 3 month for the first year and then annually. They were asked to fill questionnaires evaluating functional outcomes. The International Continence Society (ICS) score was used to assess the postoperative urinary continence. Fecal continence was evaluated with the Wexner score and sexual function was assessed with the International Index for erectile function (IIEF-5) score. RESULTS: Eighty-seven percent patients (14/16) in our series developed RUF as a consequence of prostate cancer surgery and 13% (2/16) postbrachytherapy (BT). All patients initially had a diversion colostomy and a supra pubic catheter. 69% (11/16) underwent primary YM repair and 73% (8/11) were successful. 2/3 primary failures were successfully retreated with graciloplasty. Primary gracilis flap interposition (GFI), on 3 non-irradiated patients were successful (100%). Primary GFI postbrachytherapy, no patient had recover urinary and digestive continuity. In total primary GIF was successful in 60% (3/5). Over all long term, success rate with a urinary and digestive continuity and without recurrence of the fistula was 81% (13/16). Mid term functional results were evaluated at mean follow up of 40 months (14-92). 13% (2/16) achieved complete urinary continence, 48% (7/16) required single pad, 25% (4/16) developed major incontinence, 7% (1/16) required urinary diversion and 13% (2/16) developed complete urethral closure post BT requiring permanent suprapubic catheterization. Colostomy was reversed in 93% (15/16) cases. 75% (12/16) achieved complete faecal continence, minor incontinence (wexner score 3-4) was seen in 13% (2/16) and major incontinence (wexner score 14) in 7% (1/16) and 7% (1/16) required a long term colostomy. 19% (3/16) developed colostomy related complications. Only 13% (2/16) achieved adequate erections with the use of intra cavernosal prostaglandin injections. CONCLUSIONS: RUF following prostate cancer treatment is a serious complication with severe repercussion on patients' quality of life. Surgical repair with the York Mason technique or Gracilis Flap interposition is associated with good success rates. If available pediculed gracilis muscle should be used as it offers better success rates. LEVEL OF EVIDENCE: 3.

[Eight years of experience in robot-assisted partial nephrectomy: oncological and functional outcomes]. / Huit ans d'expérience en néphrectomie partielle robot-assistée: résultats carcinologiques et fonctionnels.

INTRODUCTION: Partial nephrectomy (PN) is currently the reference treatment for renal tumors of less than 4 cm in size (T1a). Laparoscopic PN is difficult to perform, with the main consequence being an increase in warm ischemia time and morbidity. In facilitating the surgical procedure, robotics combines the benefits of minimally invasive and conservative surgery. We report here 8 years of experience with 110 robot-assisted partial nephrectomies (RAPN). The objective of this study was to analyze the oncological and functional outcomes. PATIENTS AND METHODS: Between March 2005 and September 2012, 110 patients underwent RAPN. The epidemiological and surgical data and the oncological and functional outcomes were retrospectively collected and analyzed. RESULTS: Seventy-six men and 34 women underwent surgery. The mean age was 59.6 ± 14.2 years. Mean operative time was 141.3 ± 36.1 minutes with a warm ischemia time of 21.2 ± 8.8 minutes. Mean hospital stay was 5.3 ± 2.2 days. Mean tumor size was 27.4 ± 9.8mm with 82.7% malignant tumors, of which 62.7% were clear cell carcinomas. Surgical margins were healthy in 100% of cases. After a mean follow-up of 28.7 ± 18.5 months, no recurrence was noted. On a functional level, there was no short-term or medium-term impairment of renal function. The frequency of postoperative complications was estimated as 12% including 7% of surgical complications (3 arterial pseudoaneurysms, 4 episodes of bleeding from the cut surface and 1 conversion to laparotomy). CONCLUSION: Robotics brought surgeon dexterity, meticulousness and precision. These qualities are essential in conservative renal surgery and made RAPN a safe and effective technique that gives good short and medium-term oncological and functional results.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases]. / Néphrectomie chez le donneur vivant par voie laparoscopique robot-assistée: évaluation préopératoire et résultats à partir de 100 cas.

AIM: To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. PATIENTS AND METHODS: We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. RESULTS: Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. CONCLUSION: Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%.

[In search of the surgical sperm cell: do we have to perform a testicular biopsy systematically?]. / À la recherche du spermatozoïde chirurgical : doit-on effectuer une biopsie testiculaire systématique ?

INTRODUCTION: Testicular biopsies are diagnostic and therapeutic tools involved in male infertility care. However, this surgery is invasive and not systematically successful. We studied the preoperative clinical and hormonal factors allowing to predict the obtaining of sperm cells. PATIENTS AND METHODS: A retrospective study was conducted on 209 patients who all had a testicular biopsy for procreation medically assisted (PMA). The studied criteria were: the age at the time of the surgery, the male cause of the infertility, the testicular volume, the tobacco smoking exposure, the concentrations of estradiol, FSH, LH, prolactin, and testosterone. The comparison of both groups (successful biopsy versus failed biopsy) was made in bivariate analysis then in multivariate analysis. RESULTS: The testicular volume average and the cause were the two only factors which had a real influence on the negativity of the biopsy. In it was added in bivariate analysis a statistically significant correlation of the smoking exposure and the FSH with the failed biopsy. DISCUSSION: The existence of these factors, and their accumulation, was strongly predictive of a failure of the biopsy. However, we found germ cells in patients exposed to the studied factors, letting think that it is systematically necessary to propose the surgery at the risk of a limited profit.

[Arterial anastomotic aneurysms after kidney and pancreas transplantation: diagnosis and management]. / Les anévrismes artériels anastomotiques après la transplantation rénale et pancréatique: diagnostic et traitement.

OBJECTIVE: The objective of our study was to assess the frequency, circumstances of diagnosis and treatment of anastomotic arterial aneurysms and compare them to the literature. MATERIAL AND METHOD: A single-center series of 3000 kidney transplants and 126 pancreas transplants between 1974 and 2010 was studied retrospectively. Ten patients had anastomotic arterial aneurysms: eight after kidney transplantation and two after pancreas-kidney transplantation. Diagnosis was based on the association Doppler ultrasonography-angioscanner. RESULTS: Ten arterial anastomotic aneurysms were identified. The circumstances of discovery were clinical in eight cases, half of them by hemodynamic collapsus. A majority of our patients (60%) were diagnosed in the year following the transplantation and two cases were discovered after transplantectomy. Pancreas-kidney transplantation had a high risk for arterial anastomotic aneurysm. Candida albicans was isolated in preoperative samples in four cases. The management consisted to transplantectomy in seven patients, revascularization of the lower limb in six patients and one renal transplant preservation. We found two lower limb ischemia and two deaths by a fatal intraoperative haemorrhage and vascular cerebral haemorrhage. No recurrence was identified after in the follow-up ranged from 20 months to 12 years. CONCLUSION: Arterial anastomotic aneurysm was in our study a serious complication that requires emergency surgery. The transplantectomy followed by revascularization of the limb is the treatment of choice associated to an appropriate antifungal or antibiotic treatment.

[Metabolic impact of androgen deprivation therapy for prostate cancer]. / Impact métabolique de la suppression androgénique dans le cancer de la prostate.

Because of the low mortality rates associated with prostate cancer, treatments long-term adverse effects constitute an important parameter in the management of patients. In particular, androgen deprivation has been shown to be linked to several metabolic disorders which are already frequent in men after age 60, such as weight and fat gain, insulin resistance likely to evolve into diabetes, and dyslipidemia. So far no consensus guidelines have been published regarding the screening and treatment of metabolic disorders in men with prostate cancer. It is essential to detect and manage these metabolic disorders, all the more so as they seem to be associated with an increased aggressiveness of prostate cancer. Here we report the development of a new questionnaire, which might contribute to the systematic management, and potentially the screening and treatment or the prevention of these metabolic disorders in patients with prostate cancer. In accordance with recent reviews and on the basis of experience, our French board of experts also recommends systematic screening and selective treatment for diabetes, regular follow-up of fasting glucose rates, lipid profile and blood pressure in all patients under long-term androgen deprivation treatment, as well as lifestyle changes (practice of exercise, nutritional habits).

[5 alpha-reductase inhibitors and prostate cancer: a statement of the Committee of Cancerology of the French Association of Urology]. / Inhibiteurs des 5 alpha-réductases et cancer de la prostate : une mise au point du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Two randomised trials and negative conclusion of the FDA about inhibitors of 5 alpha-reductase in prevention of prostate cancer need a revision of the indications of these drugs. METHODS: After description of fundamentals data, review of the literature in PubMed library was performed to analyse the indications of these drugs according to the different stages of prostate cancer. RESULTS: Even if PCPT and REDUCE studies showed a decrease of cancers with the use of 5 alpha-reductase (5ARI) but with side effects, there is no indication for prostate cancer prevention by these drugs. In the same way, despite the results of REEDEM study, there is no indication of these drugs in active surveillance. CONCLUSION: Despite the large interest of these drugs, no recommendation can be given for indications of 5ARI in prevention or treatment of prostate cancer.

[Ischemic lesions in kidneys after extracorporeal shock wave lithotripsy demonstrated by Proton NMR spectroscopy of urine samples]. / Évaluation par spectroscopie RMN des lésions rénales provoquées par la lithotripsie extracorporelle à partir d'échantillons d'urine.

PURPOSE: The aim of this prospective study was to investigate the effect of extracorporeal shock wave lithotripsy (SWL) on kidneys of patients with pyelic stone disease. The effects of SWL were assessed by high-resolution proton nuclear magnetic resonance (HNMR) spectroscopy of urine samples. METHODS: Twenty-three patients, aged 31-80years (mean: 55years), with pyelic stone disease were investigated before and after SWL. Multiparameter analysis was performed by HNMR spectroscopy of urine samples collected before and 5h after SWL (second miction post-SWL). RESULTS: The most relevant resonances determined by HNMR spectroscopy were acetate, lactate, trimethylamine N-oxide and amino acids. Excretion of these markers increased significantly in comparison with pre-SWL urinary samples. CONCLUSION: These results show that early ischemic damage occurs after SWL. Post-SWL. HNMR spectroscopy is an effective tool for noninvasive follow-up of renal damage.

Prognostic value of prostate circulating cells detection in prostate cancer patients: a prospective study.

In clinically organ-confined prostate cancer patients, bloodstream tumour cell dissemination generally occurs, and may be enhanced by surgical prostate manipulation. To evaluate cancer-cell seeding impact upon patient recurrence-free survival, 155 patients were prospectively enrolled then followed. Here, 57 patients presented blood prostate cell shedding preoperatively and intraoperatively (group I). Of the 98 preoperatively negative patients, 53 (54%) remained negative (group II) and 45 (46%) became intraoperatively positive (group III). Median biological and clinical recurrence-free time was far shorter in group I (36.2 months, P<0.0001) than in group II (69.6 months) but did not significantly differ in group II and III (69.6 months vs 65.0). Such 5-year follow-up data show that preoperative circulating prostate cells are an independent prognosis factor of recurrence. Moreover, tumour handling induces cancer-cell seeding but surgical blood dissemination does not accelerate cancer evolution.

Prostate-specific antigen bounce in patients treated before 60 years old by iodine 125 brachytherapy for prostate cancer is frequent and not a prognostic factor.

PURPOSE: The only prognostic factor of prostate-specific antigen (PSA) bounce in prostate cancer found in several studies is young age but has never been specifically studied in this subset of patients for long-term results. Bounce characteristics, histological, clinical, and dosimetric data in young patients were analyzed, as well as their impact on toxicity and survival. MATERIAL AND METHODS: This retrospective study included patients aged ≤60 years treated with exclusive iodine 125 brachytherapy with low or intermediary prostate adenocarcinoma during 1999-2014. Exclusion criteria were a follow-up of ≤24 months. PSA bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. RESULTS: This study analyzed 179 patients. Median age was 56 years (46-59 years). The median follow-up was 79 months (54; 123). The bounce incidence was 56.8% (49.6%; 64.2%) at 5 years, inversely proportional to positive/total biopsies ratio (HR 0.98, 95% CI [0.97, 0.99]). Incidence of biochemical failure was 1.2%, 95% CI (0.3%; 4.7%), at 5 years with no difference between the bounce and no-bounce group (HR 0.96, 95% CI [0.25; 3.58]). Bounce is an unfavorable prognostic factor for grade two and three urinary toxicities 6.67 (4.14; 10.76) (p < 0.001). CONCLUSIONS: PSA bounce is common in young people after brachytherapy. It should be monitored without starting an inadequate and sometimes invasive relapse checkup or a relapse treatment.

Expression of prostate-specific membrane antigen in transitional cell carcinoma of the bladder: prognostic value?

The expression of Prostate-specific membrane antigen (PSMA) mRNA was assessed in the normal bladder urothelium (n = 9), transitional cell carcinoma (TCC) specimens (n = 52), TCC-derived cell lines (n = 3), and preoperative blood samples from TCC patients (n = 27). Specific PSMA mRNA was found in 100% of normal and malignant tissues and two cell lines. PSMA protein was detected in normal (n = 3) and malignant tissues (n = 4). Using a PSMA-specific substrate, PSMA enzymatic activity was found in two bladder cell lines and correlated with immunostaining. Seven of the 27 TCC preoperative blood samples were positive by reverse transcription-PCR. These preliminary results, obtained on a nonrandomized cohort of patients, correlated with tumor invasion (positive RT-PCR: 0% for pT < or = 2 versus 41% for pT > or = 3) and 2-year survival rate (81% in the PSMA-negative group versus 29% in the PSMA-positive group). Although the clinical usefulness of this assay requires confirmation in larger prospective randomized trials, current preliminary results suggest that a blood-borne PSMA mRNA PCR assay may be a useful tool to predict a poor outcome in TCC patients.

Abnormal E-cadherin expression and prostate cell blood dissemination as markers of biological recurrence in cancer.

Until now, no molecular parameter has been available for predicting the metastatic potential of prostate tumours, which leaves their outcome uncertain despite an apparent benign histology or early stage. Abnormal expression of adhesion molecules, such as E-cadherin, can be contributing factors for increased invasiveness and metastatic potential. Histological analysis for E-cadherin expression was carried out on paraffin-embedded tumour tissues. Tumour metastatic potential was indirectly evaluated by detecting circulating prostate cells (CPC), using reverse transciptase-polymerase chain reaction (RT-PCR) and prostate-specific membrane antigen (PSMA) as a target. Patients were followed-up for a median of 14 months (range 10--19 months) after surgery with serum prostate-specific antigen (PSA) level measurement. Interestingly, 23 of 44 localised tumours exhibited aberrant E-cadherin expression. Prior to primary surgery, PSMA RT-PCR detected the spread of prostate cells to the blood in 24 patients. Statistical analysis showed that abnormal E-cadherin expression in the tumours was the only variable that was independently correlated with prostate cell dissemination in the blood (P<0.0001). In logistic regression analysis, abnormal E-cadherin expression was a significant independent predictor for a later biological relapse. This impaired adhesion status was clearly correlated with a haematogenous spread of the primary tumour cells. It could therefore be an objective way to restrict the indications for radical surgery to patients not presenting with this feature.

Clonal analysis of renal sporadic angiomyolipomas.

Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.