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Increased de novo fatty acid (FA) synthesis is one hallmark of tumor cells, including prostate cancer. We present here our most recent results showing that lipid composition in human prostate cancer is characterized by an increased ratio of monounsaturated FA to saturated FA, compared with normal prostate, and evidence the overexpression of the lipogenic enzyme stearoyl-CoA desaturase 1 (SCD1) in human prostate cancer. As a new therapeutic strategy, we show that pharmacologic inhibition of SCD1 activity impairs lipid synthesis and results in decreased proliferation of both androgen-sensitive and androgen-resistant prostate cancer cells, abrogates the growth of prostate tumor xenografts in nude mice, and confers therapeutic benefit on animal survival. We show that these changes in lipid synthesis are translated into the inhibition of the AKT pathway and that the decrease in concentration of phosphatidylinositol-3,4,5-trisphosphate might at least partially mediate this effect. Inhibition of SCD1 also promotes the activation of AMP-activated kinase and glycogen synthase kinase 3α/β, the latter on being consistent with a decrease in β-catenin activity and mRNA levels of various β-catenin growth-promoting transcriptional targets. Furthermore, we show that SCD1 activity is required for cell transformation by Ras oncogene. Together, our data support for the first time the concept of targeting the lipogenic enzyme SCD1 as a new promising therapeutic approach to block oncogenesis and prostate cancer progression. Mol Cancer Ther; 9(6); 1740–54. ©2010 AACR.

Supplementary Data from Abrogation of De novo Lipogenesis by Stearoyl-CoA Desaturase 1 Inhibition Interferes with Oncogenic Signaling and Blocks Prostate Cancer Progression in Mice

Resume Objectif L’objectif de cette etude est de presenter l’evolution des donnees d’incidence et de mortalite du cancer des organes genitaux externes de l’homme dans l’Herault a partir des donnees du Registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiel et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution des tumeurs germinales du testicule (TGT) et du cancer du penis (CP) sur 30 ans (de 1987 a 2016). Nous avons analyse les donnees d’incidence et de mortalite de ces tumeurs. Nous avons compare ces resultats aux donnees francaises, europeennes et mondiales. Resultats En 30 ans d’enregistrement nous avons recense 725 cas de TGT et 175 cas de CP. Le taux standardise sur la population mondiale (TSM) d’incidence des TGT a double entre 1987 et 2016 (4,2/100 000 en 1987 et 9,3/100 000 en 2016). Il a ete multiplie par 2,63 dans la population des patients de 30 a 44 ans. On observe une baisse du taux de mortalite avec un TSM a 0,8/100 000 en 1987, et 0,4/100 000 en 2016. Le TSM d’incidence des CP est stable entre 1987 et 2016 (TSM entre 0,4 et 0,9/100 000). La mortalite est stable avec un TSM entre 0,1 et 0,3/100 000 entre 1987 et 2016. Conclusion L’incidence des TGT a fortement augmente dans l’Herault durant les 30 dernieres annees alors que l’on observe une diminution de la mortalite. La proportion des tumeurs germinales seminomateuses augmente ; elle est passee de 53 % a 60 % en 30 ans dans l’Herault. L’incidence et la mortalite du CP etaient stables dans l’Herault durant les 30 dernieres annees.

Resume Objectifs On observe dans l’Herault une nette augmentation de l’incidence des cancers urologiques. Le registre des tumeurs de l’Herault (RTH) a recueilli 1961 tumeurs urologiques en 2016, soit 21,4 % de l’ensemble des tumeurs de l’Herault pour cette annee-la. La creation d’un registre specialise en onco-urologie nous est apparue necessaire. L’objectif de cet article est de decrire le fonctionnement de RHESOU et de donner quelques exemples de resultats. Materiel et methodes En novembre 2018, RHESOU (Registre de l’herault specialise en onco-urologie) a ete cree sur le meme mode de fonctionnement qu’un registre. Il permet de completer les donnees du RTH sur beaucoup d’autres parametres oncologiques. Pour chaque type de cancer urologique et genital masculin et urologique feminin, une fiche de recueil a ete realisee pour recueillir le maximum de donnees presentes dans le dossier des cas signales. Cette etude a evalue les donnees concernant les patients domicilies dans l’Herault pour l’annee 2017. Resultats Nous avons denombre pour l’annee 2017, 970 cancers de la prostate, 581 tumeurs de vessie, 212 cancers du rein, 51 tumeurs de la voie excretrice superieure, 28 cancers du testicule et 9 cancers du penis. Le recueil de ces donnees permet de creer des requetes et de fournir des analyses pertinentes et detaillees sur les cancers urologiques et genitaux masculins. Nous rapportons les donnees analysees sur le rein, la vessie et la prostate. Conclusions RHESOU est un outil accessible pour permettre une vue d’ensemble sur les cancers en urologie dans l’Herault et leur prise en charge. Avec l’apparition de nouveaux traitements, il saura s’adapter en permettant une evolution des fiches. Niveau de preuve 3.

Summary Introduction European Randomized Study of Screening for Prostate Cancer (ERSPC) mortality results were reported for 7 European countries (excluding France) and showed a significant reduction in Prostate cancer (PCa) mortality. As those results have not been part of the global ERSPC results, it is of interest to report PCa mortality at a median follow-up of 9 years for French section of ERSPC. Material and methods Two administrative departments were involved in the study. Only men after randomization in the screening group were invited by mail to be screened by PSA testing with two rounds at 4–6 year intervals. Biopsy was recommended if PSA > = 3.0 ng/mL. No information other that the French Association of Urology recommandations on the use of PSA was offered to the control group (own decision of physicians and patients). Follow up was based on cancer registry database. Contamination defined as the receipt of PSA testing in control arm was measured. Poisson regression models were used to estimate the Rate Ratio (RR) of PCa mortality and incidence in the screening vs. control arm. Results Starting from 2003, 80,696 men aged 55–69 years were included. The percentage of men in the screening arm with at least one PSA test (compliance) was 31%. Compared to the control arm, PCa incidence increased by 10% in the screening arm (RR = 1.10; 95% CI = [1.04–1.16], P = 0.001), but PCa mortality did not differ (0.222 and 0.215 deaths/1000 person-years; RR = 1.03[0.75–1.42], P = 0.9). Discussion Limitations include low participation rate. PSA testing in the control arm was observed in 32% of men (contamination). Conclusions Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up. Level of evidence 3.

Resume Objectif L’objectif de cette etude est de presenter l’evolution de l’epidemiologie du cancer du rein dans l’Herault a partir des donnees collectees par le registre des tumeurs de l’Herault (RTH) sur une periode de 30 ans. Materiels et methodes A partir de la base de donnees du RTH, nous avons etudie l’evolution du cancer du rein de 1987 a 2016. Nous avons analyse les donnees concernant l’incidence, la mortalite, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons compare ces resultats aux donnees nationales et internationales. Resultats Nous avons recense 3769 nouveaux cas de cancers du rein: 2628 chez l’homme (69,7 %) et 1141 chez la femme (30,3 %). En 2016, le cancer du rein etait le 8e cancer tous sexes confondus, le 7e cancer chez l’homme et le 11e chez la femme. Entre 1987 et 2016 le nombre de nouveaux cas de cancer du rein a ete multiplie par 4,2 chez l’homme et par 3,3 chez la femme. Le nombre de formes localisees a augmente de 9 % en 20 ans. En 2016 la probabilite, d’etre atteint d’un cancer du rein avant 75 ans est de 2,11 % pour un homme et de 0,62 % pour une femme. Conclusion En 30 ans, l’incidence du cancer du rein a fortement augmente dans l’Herault alors que l’on observe une diminution de sa mortalite. Ces donnees analytiques seront ameliorees par le developpement du Registre de l’Herault Specialise en Onco Urologie (RHESOU) Niveau de preuve 3.

Objectifs Le registre des tumeurs de l’Herault (RTH) est un registre general qualifie par le comite national des registres depuis 1987. L’objectif de cette etude est de presenter l’evolution de l’epidemiologie du cancer de la vessie dans le departement de l’Herault a partir des donnees collectees par le RTH sur une periode de 30 ans. Methodes A partir de la base de donnees du RTH, nous avons etudie l’incidence, les taux d’incidence standardises sur la population mondiale (TSM), la frequence relative, le sex-ratio, l’âge moyen au diagnostic, les donnees anatomopathologiques et les primo-traitements pour toutes les tumeurs de la vessie ≥ T1 dans la population de l’Herault entre 1987 et 2016. Les donnees de mortalite proviennent du service SC8 de l’INSERM (CepiDC). Nous avons compare ces resultats aux donnees nationales et internationales. Les estimations francaises proviennent des donnees FRANCIM et les donnees mondiales des registres sont regroupees par le Centre international de recherche sur le cancer (CIRC), situe a Lyon. Resultats Les TSM du cancer de la vessie pour 100 000 sont passes de 11,1 en 1987–1988 (21 hommes, 3,1 femmes) a 8,2 en 2015–2016 (15,2 hommes, 2,5 femmes). Sur 30 ans, le RTH a recense 5580 cas et 2718 deces. Le rapport mortalite/incidence etait de 48,7 % (45,9 % chez l’homme, 62,1 % chez la femme) et le sex-ratio etait de 4,7 hommes pour une femme. En 2016, il etait le 7e cancer dans l’Herault (5e chez l’homme). Les carcinomes urotheliaux representaient 91,7 % des cancers. En 2016, l’âge moyen au diagnostic etait de 74,8 ans (74,2 ans chez l’homme, 76,9 ans chez la femme) et la probabilite d’avoir un cancer de la vessie avant l’âge de 75 ans etait de 1,81 % pour un homme (1/55) et 0,26 % pour une femme (1/382) ( Fig. 1 ). Discussion L’incidence des tumeurs de la vessie a faiblement diminue chez l’homme dans l’Herault. Les registres ne recueillent que les tumeurs ≥ T1, ce qui differe des recommandations cliniques. En 2018, le Registre de l’Herault Specialise en Onco-Urologie (RHESOU) a vu le jour, dans le but d’apporter plus de coherence entre les donnees epidemiologiques et la pratique clinique actuelle. Conclusion L’incidence des tumeurs de la vessie a faiblement diminue chez l’homme dans l’Herault. Les registres ne recueillent que les tumeurs ≥ T1, ce qui differe des recommandations cliniques. En 2018, le Registre de l’Herault Specialise en Onco-Urologie (RHESOU) a vu le jour, dans le but d’apporter plus de coherence entre les donnees epidemiologiques et la pratique clinique actuelle.

International audience; Although renal graft percutaneous embolization was introduced to avoid the risk associated with graft nephrectomy, there is no universal consensus about its indications and results. In order to evaluate the efficacy of graft embolization in the treatment of graft intolerance syndrome as well as its safety compared to surgical removal with respect to complications and other morbidity measures, We performed a retrospective observational study comparing two groups of patients treated for graft intolerance syndrome: Group 1: patients who had embolization as first-line treatment and Group 2: patients directly treated by surgical removal. 72 patients were included, (32 in Group 1 and 40 in Group 2); the postintervention follow-up continued for 12 months. Patients in Group 1 are older than those in Group 2. Otherwise, the two groups are similar concerning sex, manifestations of graft intolerance syndrome, diabetes and nutritional and functional status. The overall success rate of embolization in complete resolution of graft intolerance syndrome and ultimately avoidance of surgical removal was 84.37%. The surgical removal group had more serious complications, a longer hospital stay and needed more blood transfusions. We conclude that embolization of symptomatic renal grafts has considerable efficacy with less morbidity, and no serious complications compared to the standard surgical graft removal.

International audience; ObjectifsLe registre des tumeurs de l’Hérault est un registre général qualifié par le comité national des registres depuis 1987. L’objectif de cette étude est de présenter l’évolution de l’épidémiologie des cancers testiculaires dans le département de l’Hérault à partir des données collectées par le registre des tumeurs de l’Hérault (RTH) sur une période de 30 ans.MéthodesÀ partir de la base de données du RTH, nous avons étudié l’évolution des tumeurs de la vessie de 1987 à 2016. Nous avons analysé les données concernant l’incidence, la mortalité, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons comparé ces résultats aux données nationales et internationales.RésultatsNous avons recensé 729 nouveaux cas de tumeur du testicule. Le taux standardisé sur la population mondiale (TSM) de l’incidence est passé de 4,6 en 1987 à 9 en 2016 pour 100 000, la mortalité de 0,6 à 0,2 pour 100 000 pour la même période. Le pic d’incidence se situe entre 30 et 35 ans.ConclusionEn 30 ans, l’incidence des tumeurs testiculaire à fortement augmenter dans l’Hérault, on observe une faible diminution de sa mortalité sur cette même période. Ces données analytiques seront améliorées par le développement du Registre de l’Hérault Spécialisé en onco-urologie (RHESOU).

International audience; ObjectifsL’objectif de cette étude est de présenter l’évolution de l’épidémiologie du cancer du rein dans l’Hérault à partir des données collectées par le registre des tumeurs de l’Hérault (RTH) sur une période de 30 ans.MéthodesÀ partir de la base de données du RTH, nous avons étudié l’évolution du cancer du rein de 1987 à 2016. Nous avons analysé les données concernant l’incidence, la mortalité, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons comparé ces résultats aux données nationales et internationales.RésultatsNous avons recensé 3766 nouveaux cas de cancers du rein : 2626 chez l’homme (69,7 %) et 1140 chez la femme (30,3 %). En 2016, le cancer du rein était le 8e cancer tous sexes confondus, le 7e cancer chez l’homme et le 11e chez la femme. Entre 1987 et 2016, le nombre de nouveaux cas de cancer du rein a été multiplié par 4,2 chez l’homme et par 3,3 chez la femme. Le nombre de formes localisées a augmenté de 9 % en 30 ans. En 2016, la probabilité d’être atteint d’un cancer du rein avant 75 ans est de 2,11 % pour un homme et de 0,62 % pour une femme (Fig. 1).ConclusionEn 30 ans, l’incidence du cancer du rein a fortement augmenté dans l’Hérault alors que l’on observe une diminution de sa mortalité. Ces données analytiques seront améliorées par le développement du Registre de l’Hérault Spécialisé en Onco-Urologie (RHESOU).

International audience; Renal insufficiency can occur in patients with congenital lower urinary tract malformations (LUTM) even when managed during infancy. Data in the current literature concerning this subject remain sparse. The aim of this study was to report the feasibility and long-term results of renal transplantation during adulthood in patients with a congenital LUTM.Methods: A retrospective multicenter study from 3 French renal transplant centers was conducted, including 123 transplantations on 112 patients with LUTM (1996-2016). Graft survival, patient survival, and complications were analyzed. Results were stratified according to the underlying uropathy and the type of initial management during childhood or before transplantation.Results: In this study, patients suffering from posterior urethral valves (n = 49), spina bifida (n = 21), central neurogenic bladder (n = 13), bladder exstrophy (n = 14), prune belly syndrome (n = 12), Hinman syndrome (n = 6), urogenital sinus (n = 4), and other pathologies (n = 4) were included. The mean age at transplantation was 32.1 years old (±11.2). The mean follow-up period was 7.2 years. Patient survival at 1, 5, 10, and 15 years was 97.4%, 93.0%, 89.4%, and 80.0%, respectively. Graft survival at 1, 5, 10, 15, and 20 years was 96.6%, 87.6%, 77.3%, 60.6%, and 36.4%, respectively. Enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute pyelonephritis (P = 0.02). There was no difference in graft survival when transplantation was performed on an enterocystoplasty or urinary diversions compared with a native bladder, provided a well-conducted bladder management.Conclusions: Even though enterocystoplasty and continent urinary diversions exposed grafts to more frequent acute graft pyelonephritis, patient and graft survival rates in LUTM at 10 years were similar to other kidney transplantations on native bladders.

International audience; We report the natural history and prognosis of tumors after augmentation enterocystoplasty, with a molecular analysis using an oncogene panel to search for potential targeted therapies.Materials and methods: this multicenter, nationwide, retrospective study included 16 patients. A panel of 21 clinically relevant oncogenes was tested on archival tumor specimens using next-generation sequencing. Survival rate was the main clinical outcome and sequences were compared to the reference genome for the genetic outcome.Results: augmentation enterocystoplasties were performed mainly for congenital neurogenic bladder and bladder exstrophy at a median patient age of 17 years (range 4 months to 45 years). Most of the malignancies were diagnosed because of clinical manifestations, with a median latency period of 20 years. Adenocarcinomas were mainly found after gastrocystoplasty, whereas urothelial cell carcinomas were typically found after colocystoplasty. Of the 16 patients 13 were diagnosed at an advanced stage of the disease (positive lymph nodes in 7, distant metastases in 6). The overall 1-year survival rate was 56%. Only 3 patients remained disease-free at a median followup of 70 months. Of the 9 tumors with analyzable DNA 4 were wild-type and 5 harbored missense mutations (KIT-p.Pro573Ser, PDGFRA-p.Glu587Lys, KRAS-p.Gly12Asp, ERBB4p.Arg484Lys, CTNNB1-p.Ser37Phe and p.Ser47Asn).Conclusions: malignancy after augmentation enterocystoplasty is diagnosed late with frequent metastases and a very low 1-year survival rate. More than half the tested samples harbored missense mutations in oncogenes accessible to targeted therapies. An international collaboration to enlarge the genetic panel analysis of these tumors may offer new therapeutic hope to patients.

International audience; PURPOSE: The objective of this study was to compare living-donor kidney transplantation (LDKT) performed either sequentially, in one operating room, leading to extended cold ischemia time (CIT) or simultaneously, in two different operating room, with shorter CIT.METHODS: We retrospectively included all living-donor nephrectomies and kidney transplantations, performed from March 2010 to March 2014, in three French university centers. In the first one (C1), LDKTs were performed in sequential manner (Sequential group) and in C2 and C3, LDKTs were performed in simultaneous manner (Simultaneous group).RESULTS: A total of 324 LDKT were performed: 176 LDKT in Sequential group and 148 LDKT in Simultaneous group. Patients characteristics were equivalent between groups, except nephrectomy side, ABO mismatch rate and previous kidney transplantation rate. CIT, rewarming time, transfusion and delayed graft function (DGF) were significantly higher in Sequential group. Overall survival and graft survival of kidney transplant recipients were similar in the Sequential and Simultaneous groups. 5-year eGFR was similar between groups. In univariate analysis, number of graft arteries, recipient BMI, previous kidney transplantation status and CIT were significant predictors of DGF. Only previous kidney transplantation status was an independent predictive factor of DGF in the multivariate analysis.CONCLUSIONS: Sequential surgical organization results in the same functional results as simultaneous surgical organization. DGF was higher for LDKT performed sequentially but at 5-year overall survival, graft survival and eGFR were similar between these two types of transplant organizations.

Resume Objectif Analyser les resultats des reprises chirurgicales pour complication ureterale (stenose ureterale ou fistule urinaire) apres transplantation renale sur une periode de 10 ans. Materiels et methodes Nous avons realise une etude retrospective portant sur 1313 transplantations renales consecutives realisees dans un centre hospitalo-universitaire entre 2005 et 2014. Les donnees des patients ayant developpe une stenose ureterale ou une fistule urinaire secondaire a une transplantation renale ont ete analysees. Les transplantations d’organes combinees (rein-foie et rein-pancreas), ainsi que les transplantations pediatriques ont ete exclues. Resultats Soixante-16 patients (5,8 %) ont developpe une stenose ureterale ou une fistule urinaire apres transplantation renale. Quarante-six patients (3,5 %) ont eu une reprise chirurgicale : 27 pour stenose ureterale, 19 pour fistule urinaire. Un succes d’emblee de ces reprises a ete obtenu pour 26 patients (56,5 %), dont 14 stenoses ureterales (51,9 %) et 12 fistules urinaires (63,2 %) (p = 0,45). Apres un nouveau traitement endoscopique ou chirurgical, le taux de succes definitif a ete porte a 73,1 % (34 patients) : 20 stenoses ureterales (74,1 %) et 14 fistules urinaires (73,7 %) (p = 0,98). Il y a eu 2 pertes de greffons (4,3 %) et un deces (2,2 %). Le debit de filtration glomerulaire moyen estime par le calcul du MDRD etait a 44,58 mL/min/1,73 m2 (±14,7) avant la reprise et a 45,37 mL/min/1,73 m2 (±16,5) 6 mois apres la reprise (p = 0,92). Conclusion Bien que souvent complexes, les reprises chirurgicales pour complication ureterale apres transplantation renale donnent de bons resultats, avec un faible taux de perte de greffons et de mortalite. Niveau de preuve 4.

INTRODUCTION AND OBJECTIVES:The aim of this study is to describe the natural history, the prognosis and the molecular analysis of a panel of cancer genes on a large series of patients with malignan...

Resume Introduction Un nombre important de patients atteints d’un cancer de la prostate (CP) est diagnostique et traite. L’objectif de cette etude est d’analyser, deux ans apres traitement, l’incontinence urinaire (IU) et les dysfonctionnements sexuels (DS) pouvant affecter les patients. Methodes Cette etude a suivi tous les cas de CP localise, diagnostiques entre 2008–2009, chez les hommes d’âge ≤ 65 ans en vie deux ans apres traitements. Quatre cent trente-sept personnes ont ete incluses dans l’enquete. Les donnees ont ete collectees par un questionnaire et par croisement avec les donnees du registre des cancers. Une analyse descriptive et comparative de la persistance des sequelles a deux ans a ete effectuee. Resultats A deux ans du traitement, l’IU a persiste pour 48,8 %, 41,2 % ont eu recours a des protections urinaires ; 39,2 % portaient au moins une protection/jour ; 55,2 % ont eu des difficultes financieres a l’achat des protections. Au total, 22,7 % n’ont pas consulte de specialiste pour l’IU. Les DS ont persiste pour 82,8 % ; 30,4 % n’ont pas consulte de specialiste. Les DS ont eu un impact negatif sur la vie sexuelle des patients et de leurs partenaires. Apres ajustement sur le stade, seule la prostatectomie est significativement associee a la persistance de l’IU et de la DS. Conclusion Le pourcentage de patients ayant une IU et/ou une DS persistante reste eleve. La persistance de ces sequelles a ete associee a la prostatectomie. Les differences de toxicites entre traitements doivent etre presentees aux patients avant toute prise en charge afin d’engager le patient dans une demarche de decision partagee.

International audience; ObjectifsL’objectif de cette étude est de présenter l’évolution de l’épidémiologie du cancer de la prostate dans l’Hérault à partir des données collectées par le registre des tumeurs de l’Hérault (RTH) sur une période de 30 ans.MéthodesÀ partir de la base de données du RTH, nous avons étudié l’évolution du cancer de la prostate de 1987 à 2016. Nous avons analysé les données concernant l’incidence, la mortalité, l’anatomopathologie des tumeurs et leur stade au diagnostic. Nous avons comparé ces résultats aux données nationales et internationales.RésultatsNous avons recensé 21 261 nouveaux cas de cancers de la prostate. Entre 1987 et 2016 le nombre de nouveaux cas de cancer de prostate a été multiplié par 2,8 avec un pic d’incidence en 2003. Le taux standardisé sur la population mondiale (TSM) de l’incidence est passé de 32,4 à 90,3 pour 100 000, la mortalité de 13,2 à 11,5 pour 100 000. Entre 2007 et 2015, le nombre cancer diagnostiqué au stade métastatique est passé de 5,1 % à 8,5 %, de même le taux de pT3 est passé de 17 % à 27,4 %. En 2016, la probabilité d’être atteint d’un cancer de prostate avant 75 ans est de 12,28 % (Fig. 1).ConclusionEn 30 ans, l’incidence du cancer de la prostate a fortement augmenté dans l’Hérault alors que l’on observe une diminution de sa mortalité. Ces données analytiques seront améliorées par le développement du Registre de l’Hérault Spécialisé en Onco-Urologie (RHESOU).

Chronic inflammation may play a role in prostate cancer carcinogenesis. In that context, our objective was to investigate the role of nonsteroidal anti‐inflammatory drugs (NSAIDs) in prostate cancer risk based on the EPICAP data. EPICAP is a population‐based case–control study carried out in 2012–2013 (département of Hérault, France) that enrolled 819 men aged less than 75 years old newly diagnosed for prostate cancer and 879 controls frequency matched to the cases on age. Face to face interviews gathered information on several potential risk factors including NSAIDs use. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using unconditional logistic regression models. All‐NSAIDs use was inversely associated with prostate cancer: OR 0.77, 95% CI 0.61–0.98, especially in men using NSAIDs that preferentially inhibit COX‐2 activity (OR 0.48, 95% CI 0.28–0.79). Nonaspirin NSAIDs users had a decreased risk of prostate cancer (OR 0.72, 95% CI 0.53–0.99), particularly among men with an aggressive prostate cancer (OR 0.49, 95% CI 0.27–0.89) and in men with a personal history of prostatitis (OR 0.21, 95% CI 0.07–0.59). Our results are in favor of a decreased risk of prostate cancer in men using NSAIDs, particularly for men using preferential anti‐COX‐2 activity. The protective effect of NSAIDs seems to be more pronounced in aggressive prostate cancer and in men with a personal history of prostatitis, but this needs further investigations to be confirmed.

Objectives To determine the impact of renal graft nephrectomy on second kidney transplantation survival. Methods We carried out a retrospective single-center study by analyzing cases performed from January 2000 to December 2011. Retransplanted patients who underwent previous allograft nephrectomy more than 3 months post-transplantation (group 1) were compared with those who did not (group 2) in terms of graft survival, incidences of acute rejection and delayed graft function. Multivariate Cox proportional hazard models were used to assess risk factors of graft loss after retransplantation. Results Overall, 146 patients were analyzed, including 52 (35.6%) in group 1 and 94 (64.4%) in group 2. Group 1 patients presented a significantly shorter first graft survival (0.8 vs 8.6 years, P

Les cancers primitifs de l’uretre sont rares. Les donnees de la litterature sont limitees, et les recommandations sont de grades B et C. Un traitement conservateur peut etre propose pour les lesions localisees de l’uretre anterieur. Les lesions localement evoluees et celles de l’uretre posterieur relevent d’une therapie multimodale qui doit etre discutee en reunion multidisciplinaire.

Objectifs L’objectif etait de comparer les resultats des transplantations renales de donneurs vivants (TRDV) realisees soit sequentiellement, dans une seule salle d’operation, entrainant une augmentation de l’ischemie froide (IF), soit simultanement, dans deux salles d’operation differentes, avec une IF plus courte. Methodes Nous avons inclus retrospectivement toutes les nephrectomies et TRDV, realisees de mars 2010 a mars 2014, dans trois centres universitaires francais. Dans le premier (C1), les TRDV ont ete realisees de maniere sequentielle (groupe sequentiel) et dans les deux autres (C2 et C3), les TRDV ont ete realisees de maniere simultanee (groupe simultane). Resultats Au total, 324 TRDV ont ete effectues : 176 TRDV dans le groupe sequentiel et 148 TRDV dans le groupe simultane. Les caracteristiques des patients etaient similaires dans les deux groupes, a l’exception du cote gauche de la nephrectomie, de l’incompatibilite ABO et du taux de TR anterieure, qui etaient plus eleves dans le groupe sequentiel. L’IF, l’ischemie tiede, le taux de transfusion et le taux de retard de reprise de fonction (RRF) etaient statistiquement plus eleves dans le groupe sequentiel. La creatinemie, la clairance de la creatinine et la survie des transplants etaient equivalents a un an et a cinq ans. A l’analyse univariee, aucun facteur predictif de fonction renale sous-optimale ( Conclusion L’organisation chirurgicale sequentielle presente les memes resultats fonctionnels que l’organisation chirurgicale simultanee. Le taux de RRF etait plus eleve pour les TRDV effectuees sequentiellement, mais a 5 ans, la survie des transplants et la clairance etaient similaires.

Objectifs Les neoplasies sont la troisieme cause de mortalite chez les transplantes renaux et l’immunosuppression est reconnue comme facteur favorisant. Les tumeurs urotheliales du transplant restent anecdotiques et peu de cas sont rapportes dans la litterature. L’objectif de cette etude a ete d’evaluer l’incidence et la morbi-mortalite de ces tumeurs. Methodes Nous avons realise une etude multicentrique retrospective dans 15 centres francais membre du CTAFU. Entre le 01 janvier 1997 et le 31 decembre 2018 nous avons recense 31 543 transplantations renales (transplantations combinees exclues). Huit patients ont eu une tumeur de la voie excretrice du transplant. Nous avons recueilli les donnees clinicobiologique de la tumeur au diagnostic initial, les modalites des traitements, les donnees de l’immunosuppression et du devenir oncologique des patients ainsi que le devenir du transplant. L’objectif principal a ete l’incidence de ces tumeurs. Les objectifs secondaires ont ete l’etude de la survie des patients et du devenir des transplants. Resultats L’incidence etait de 25 pour 100 000 sur 21 ans. Le delai median entre la transplantation et le diagnostic de tumeur etait de 107 mois (7 a 202 mois). L’âge median au diagnostic etait de 61,5 ans. Cinquante pour cent presentait un carcinome urothelial de stade ≥ pT2. Sept patients ont eu un traitement chirurgical dont 4 nephro-ureterectomies avec arret des immunosuppresseurs, 1 ureterectomie segmentaire et 1 vaporisation laser. Un patient a eu une ureterectomie segmentaire premiere puis une transplantectomie pour recidive. Un patient etait metastatique et a eu une chimiotherapie palliative. Avec un suivi median de 37,59 mois, la survie globale etait de 85,7 % [IC95 % : 33,4–97,8] a 36 mois. Trois patients ont garde un transplant fonctionnel apres traitement conservateur. Conclusion Dans la population des transplantes renaux, les tumeurs urotheliales du transplant sont rares et nous rapportons la plus importante serie sur une population caucasienne. La transplantectomie reste le traitement de reference pour la majorite des patients.

Resume Introduction L’objectif de cet article a ete d’etablir par le groupe organes genitaux externes du CCAFU des recommandations pour le diagnostic, le traitement et le suivi des tumeurs germinales du testicule. Materiel et methodes Le groupe de travail multidisciplinaire a etudie les recommandations precedentes, revue de maniere exhaustive la litterature, evalue les references, leur niveau de preuve afin d’attribuer des grades de recommandation. Resultats Le bilan initial d’un cancer du testicule repose sur un bilan clinique, biologique (AFP, hCG totale, LDH) et d’imagerie (echographie scrotale et tomodensitometrie thoracoabdomino-pelvienne). L’orchidectomie par voie inguinale est la premiere etape therapeutique permettant de preciser le type histologique, de definir le stade local et les facteurs de risque de micrometastases. La prise en charge des tumeurs de stade I repose sur une attitude therapeutique adaptee au risque en exposant au patient le benefice/inconvenient d’un traitement actif ou d’une surveillance en fonction du risque de rechute. Pour les TGS de stade I, le choix se fait entre une surveillance, une chimiotheraoie (1 cycle de carboplatine) ou une radiotherapie lombo-aortique. Pour les TGNS de stade I, le choix se fait entre une surveillance, une chimiotherapie (2 cycles de BEP) ou une lymphadenectomie retroperitoneale de stadification. La prise en charge des tumeurs metastatiques est dominee par une chimiotherapie par 3 ou 4 cycles de BEP en fonction du groupe pronostique. Dans les cas de TGS avec une atteinte metastatique ganglionnaire La reevaluation 3 a 4 semaines postchimiotherapie repose essentiellement sur le dosage des marqueurs tumoraux et la tomodensitometrie thoraco-abdomino-pelvienne. Un curage chirurgical retroperitonal est indique pour toutes les masses residuelles des TGNS > 1 cm ; et pour les masses residuelles persistantes des TGS > 3 cm ayant une fixation au TEP-TDM au 18FDG. Conclusions Les tumeurs germinales beneficient d’un excellent taux de survie base sur une classification initiale precise, un traitement adapte et codifie, et une surveillance stricte.

An increasing number of patients with prostate cancer (PC) are diagnosed and treated. The aim of this study was to investigate urinary incontinence (UI) and sexual dysfunction (SD) two years after treatment for localized prostate cancer (PC).This study followed all cases of localized PC diagnosed between 2008 and 2009 in men aged≤65years old and still alive two years after treatment. In total, 437 men were recruited. Data were collected using a standardized questionnaire and by cross-checking with data from the cancer registry. Descriptive and comparative analyses were performed to evaluate persisting UI and SD at 2years.At two years after treatment, UI was persistent in 48.8%; 41.2% had used urinary protections, and 39.2% had used at least 1 pad/day; 55.2% reported financial difficulties for purchasing protective pads. In total, 22.7% did not consult a specialist for UI. SD was persistent in 82.8%; 30.4% did not consult a specialist for SD. SD had a negative impact on the sex life of patients and their partners. After adjustment for cancer stage, prostatectomy was significantly associated with persisting UI and SD at two years.Two years after treatment, rates of persisting UI and/or SD remain high. Treatment by prostatectomy was significantly associated with an increased risk of persisting adverse effects at two years. The different toxicities between treatments should be presented to patients before initiating therapy in order to encourage the patient to contributed to shared treatment decision-making.

The association between marital status and tumor stage and grade, as well as overall mortality (OM) and cancer-specific mortality (CSM) received little attention in patients with squamous cell carcinoma of the penis (SCCP).We relied on the surveillance, epidemiology, and end results (SEER) 17 database to identify patients diagnosed with primary SCCP. Logistic and Cox regression models, respectively, addressed the effect of marital status on the rate of locally advanced disease and its effect on OM and CSM. Covariates consisted of age, race, socioeconomic status, year of surgery, and SEER registries.Between 1988 and 2006, 1,884 patients with SCCP were identified. At surgery, 1,192 (63.3 %) were married and 966 (51.3 %) had locally advanced disease. In multivariable logistic regression models predicting locally advanced disease at surgery, unmarried men had a 1.5-fold higher (p 0.001) risk than others. In multivariable Cox models predicting CSM, marital status had no effect [hazard ratio (HR) = 1.3, p = 0.1]. Finally, in multivariable Cox models predicting OM, unmarried men had a 1.3-fold higher (p = 0.001) risk than others.Unmarried men tend to present with less favorable disease stage at SCCP. Moreover, unmarried men tend to live less long than their married counterparts. However, marital status has no effect on CSM.

What's known on the subject? and What does the study add? The European Association of Urology (EAU) guidelines recommend an inguinal lymph node dissection (ILND) in patients with T1G2-3 squamous cell carcinoma of the penis (SCCP). To date, only four series reported the rates of cancer-specific mortality (CSM) after primary tumor excision (PTE) without an ILND in patients with T1 clinically node-negative (cN0) SCCP. We examined CSM rates in cN0 patients with T1G1-3 SCCP, in whom an ILND was not performed, relying on competing-risks analyses. OBJECTIVE • To quantify and compare cancer-specific mortality (CSM) and other-cause mortality (OCM) in individuals with stage T1G1–3 clinically node-negative (cN0) squamous cell carcinoma of the penis (SCCP) since there is no consensus regarding the need for an inguinal lymph node dissection (ILND) in patients with T1G2–3 cN0 SCCP. METHODS • Relying on the Surveillance, Epidemiology and End Results database, we identified 655 patients diagnosed with primary SCCP between 1988 and 2006. • Cumulative incidence plots were used to graphically depict the effect of CSM relative to OCM. • Competing-risks regression analyses were used to quantify the risk of CSM or OCM after adjusting for age, race, tumour grade and surgery type. RESULTS • The 5-year CSM rates after a primary tumour excision without ILND were 2.6%, 10.0% and 15.9% in patients with respectively T1G1, T1G2 and T1G3 cN0 SCCP. • The 5-year OCM rates were 29.5%, 27.3% and 29.3% in patients with respectively T1G1, T1G2 and T1G3. • Age failed to provide additional stratification. CONCLUSIONS • The CSM rate was highest in T1G3 patients and appears to justify ILND. • Conversely, the CSM rate was lowest in T1G1 patients, which justifies active surveillance in this patient subset. • A moderate CSM rate at 5 years was recorded for T1G2 patients, which brings into question the benefits of ILND.

To evaluate the pathologic features of surgical specimens after radical prostatectomy in patients with low-risk prostate cancer fulfilling the strictest pathologic selection criteria for active surveillance.Retrospective analysis of 10 785 consecutive radical prostatectomy performed in 10 university hospitals (January 2003 through December 2008). A total of 919 patients fulfilled the following unique and very stringent criteria: T1c, prostate-specific antigen (PSA)10 ng/mL, a single positive biopsy, tumor length3 mm, and Gleason score7. Clinico-biologic and pathologic data at diagnosis and after radical prostatectomy, prostatic and tumor volume, pathologic Gleason score and stage, positive surgical margins, insignificant prostate cancer, and PSA outcomes were recorded.Median age was 63 years. Mean prebiopsy PSA level was 6.2 ng/mL. At radical prostatectomy, Gleason score was upgraded in 34% of patients, including 1.2% Gleason score 8-9. Pathologic stages were pT2 in 87.3%, pT3 in 11.1%, and pT4 in 1.4% of cases. Extraprostatic extension was found in 12.5%. Only 26% of patients had "insignificant" tumors. Biochemical recurrence-free survival at 5 years was 92.3%. There was no significant difference in survival between patients with "significant" and "insignificant" tumors (90.1% vs 93.4%; P = .06).Despite of a stringent selection of patients with low-risk prostate cancer, active surveillance definition included a significant proportion of patients with upstaged (about 12%) and upgraded (about one-third) disease at diagnosis. Only a quarter of active surveillance patients have a pathologically confirmed "insignificant" cancer.

Objectifs L’acces a la transplantation renale a longtemps ete refuse aux patients porteurs d’une uropathie malformative du bas appareil urinaire. Les progres de la prise en charge pediatrique de ces patients leur ont donne un acces plus facile a la transplantation. Les donnees dans la litterature a ce sujet restent rares. L’objectif de cette etude a ete l’evaluation de la faisabilite et les resultats de la transplantation renale dans les uropathies malformatives du bas appareil urinaire. Methodes Il s’agit d’une etude retrospective multicentrique dans 3 centres francais de transplantation renale (Montpellier, Nantes et Lyon). Entre le 1er janvier 1996 et le 1er septembre 2016, 123 transplantations chez 112 patients porteurs d’une uropathie malformative du bas appareil urinaire ont ete realisees. Ont ete recueillies les donnees concernant les donneurs, les receveurs, et les aspects techniques de la transplantation. L’objectif principal a ete l’analyse de la survie des patients et des greffons. L’objectif secondaire a ete l’analyse des complications chirurgicale et infectieuse. La population a ete segmentee en fonction du type d’uropathie, et en fonction des gestes urologiques realisee dans l’enfance ou en preparation a la greffe. Resultats Ont ete inclus 49 valves de l’uretre posterieur, 21 spina bifida, 13 vessies neurologiques centrales, 14 exstrophies vesicales, 12 syndromes de prune belly, 6 syndromes de Hinman, 4 sinus uro-genitaux et 4 autres pathologies vesicales. Quatorze transplantations ont ete realisees sur enterocystoplastie d’agrandissement, 15 sur derivation urinaire continente, 29 sur derivation urinaire incontinente et 65 sur vessie native rehabilitee. Pour l’ensemble des groupes (n = 123), la survie des patients a 1, 5, 10 et 15 ans est de 97,48 %, 93,01 %, 89,39 % et 80,04 %. La survie specifique des greffons a 1, 5, 10, 15 et 20 ans est de 96,65 %, 87,62 %, 77,31 %, 60,63 % et 36,43 % toutes pathologies confondues. Les enterocystoplasties et les derivations urinaires incontinentes exposent significativement aux pyelonephrites aigue du greffons (p = 0,02). Il n’y a pas de difference sur la survie des greffons transplantes sur enterocystoplastie, sur derivations urinaires continente ou incontinente et sur vessie native ( Fig. 1 ). Conclusion La survie des patients et des greffons dans la transplantation renale sur uropathie malformative du bas appareil est similaire a celle de la population generale transplantee. Les aspects techniques chirurgicaux et les complications infectieuses n’influencent pas la survie des transplants renaux. Ainsi, il n’y a donc pas de restriction pour l’acces a la transplantation renale chez ces patients.

Les cancers du penis sont rares. Leur incidence est variable selon les pays. En Europe comme aux Etats-Unis, l’incidence est estimee a 1 pour 100 000 hommes [1]. Il existe des variations d’incidence entre les differents pays europeens et dans le monde avec des taux plus eleve chez les hispaniques, au Bresil et en Ouganda [2]. Il existe un role preventif de la circoncision dans la periode perinatale ou avant la puberte, mais pas lorsqu’elle est realisee a l’âge adulte. Cette circoncision precoce diminue de 3 a 5 fois le risque de cancer du penis [3]. Le cancer du penis est classiquement une pathologie du sujet âge avec une incidence qui augmente avec l’âge. Le pic de frequence est situe entre 60-70 ans. Les facteurs de risque (Odds Ratio > 10) sont principalement lies a une maceration et a un manque d’hygiene locale consecutif a un phimosis. Les autres facteurs de risques sont : .inflammation chronique (balanopostite, lichen scleroatrophique) ; .photochimiotherapie avec utilisation de sporalene et d’ultraviolet A. Les habitudes sexuelles (partenaires multiples, premier rapport sexuel precoce) et des antecedents de condylomes sont associes a une augmentation de 3 a 5 fois du risque de cancer du penis [4]. L’ADN du Human Papilloma Virus (HPV) a ete identifie dans 70-100 % des neoplasies intra-epitheliales et dans 4050 % des tumeurs infiltrantes. L’HPV-16 et HPV-18 sont des sous-types d’HPV ayant un role dans 50 % des cas du cancer du penis [5]. Il n’y a aucune recommandation actuelle chez l’homme pour une vaccination a HPV-16 et HPV-18, tant que les resultats de la vaccination chez la femme ne seront pas connus. [6] Meme s’il existe une association forte entre l’HPV et le cancer du penis, il n’y a pas de correlation entre l’infection a HPV et le risque evolutif de la tumeur.

Le cancer du testicule est rare, mais avec une prise en charge adaptee, le taux de survie specifique a 5 ans de cette maladie est superieur a 90 %, tous stades confondus [1,2]. Dans ces recommandations, ne seront traitees que les tumeurs germinales testiculaires (TGT) comprenant les tumeurs germinales seminomateuses (TGS) et les tumeurs germinales non-seminomateuses (TGNS) qui restent les plus frequentes (95 % des cas).

The adherence rate to National Cancer Institute (NCI) recommendations regarding inguinal lymph nodes dissection (ILND) in high grade T1 (G3T1) and T2-4 squamous cell carcinoma of the penis (SCCP) is not known. We assessed ILND rates in a North American cohort. The 17 registries of the Surveillance, Epidemiology, and End Results (SEER) database included 868 patients with SCCP, diagnosed between 1988 and 2006. Analyses consisted of univariable and multivariable logistic regression models. Overall, 27.6% of patients underwent an ILND. ILND rates were directly proportional with T stage: 19.0%, 30.5%, 30.6%, and 32.6% for, respectively, G3T1, T2, T3, and T4 SCCP (chi-square trend, P = 0.01). ILND rates also increased over time and were 19.3, 27.3, 30.7, and 30.8% for respectively, 1988–1995, 1996–2000, 2001–2003, and 2004–2006 periods (chi-square trend, P = 0.03). Finally, ILND rates decreased with patient age and were 42.6, 33.2, 24.7, and 7.3% for, respectively, patients aged ≤57, 58–68, 69–78 and ≥79 years of age (chi-square trend, P

Resume Introduction Le principe et la mise en œuvre d’un depistage de masse du cancer de prostate restent encore aujourd’hui controverses et rendent necessaire la realisation d’une etude d’envergure. L’etude randomisee europeenne de depistage du cancer de la prostate (ERSPC) a debute en 1994. Huit pays, dont la France, y participent. Methodologie L’ERSPC est une etude clinique randomisee controlee multicentrique qui a ete mise en place afin de demontrer une baisse de la mortalite par cancer de la prostate de 20 % suite a la realisation d’un depistage par dosage du PSA. Les hommes âges de 55 a 69 ans residant dans le Tarn ou dans l’Herault pouvaient etre inclus. Apres randomisation et exclusion des deces et des cas de cancer connus, les hommes du groupe depiste ont ete invites a donner leur consentement et a realiser un dosage du PSA. En cas de resultat positif (PSA ≥ 3 ng/ml) la realisation d’une biopsie prostatique etait recommandee. Tous les hommes inclus dans l’etude (groupe randomise et groupe temoin) ont ete suivis par les registres de cancer departementaux. L’objectif de ce travail est de presenter un etat des lieux du premier tour de depistage de la contribution francaise a l’ERSPC, de determiner quels etaient les facteurs de participations et de comparer les cas de cancer diagnostiques dans les differents groupes de randomisation. Resultats L’effectif analyse etait de 84 781 hommes dont 42 590 dans le bras depistage et de 42 191 dans le bras temoin. Le taux de participation etait de 36,9 % dans le Tarn et de 24,3 % dans l’Herault. Le PSA etait superieur a 3 ng/ml dans 15,4 % des cas ( n = 1812) et 45,9 % des hommes ( n = 832) ont effectue une biopsie. L’âge, la realisation prealable d’un dosage du PSA dans les deux ans, la caisse d’affiliation et le departement de residence etaient significativement associes a la participation a l’ERSPC. L’incidence cumulee avec un suivi de quatre ans etait de 2,48 % ( n = 1053) dans le groupe depiste et 1,99 % ( n = 840) dans le groupe temoin avec un risque relatif (RR) de 1,242. Les RR correspondants pour les effectifs separes du Tarn et de l’Herault etaient de 1,37 et 1,20. Les caracteristiques cliniques et la prise en charge therapeutique des cas de cancers etaient similaires dans le groupe depiste et dans le groupe temoin (68 % de prostatectomie et 20 % de radiotherapie). Conclusion Le taux de participation au premier tour de la contribution francaise a l’ERSPC etait modeste. Les sujets qui ont participe ne presentaient pas le meme profil que les non participants. Le groupe temoin a ete probablement contamine par la realisation de dosages de PSA hors protocole. Les consequences a l’echelle europeenne de cette faible participation et de cette contamination sur l’analyse de la diminution de la mortalite par cancer de la prostate restent a determiner.

Identification of prognostic factors in renal cell carcinoma is very important today for three goals: providing patient information, giving appropriate treatments and selecting patients for adapted treatment schedules as well as new clinical trials. Prognostic factors in RCC include: anatomical (TNM classification), histological (Fuhrmann grade and histological subtype), clinical (symptoms and performance status) and molecular factors. For improving predicative accuracy of prognostic systems such as the TNM classification, new prognostic algorithms or nomograms have been designed combining independent prognostic variables. UISS and SSIGN are the 2 most effective prognostic systems within localized RCC. In metastatic disease, the two main systems that have been used for predicting response to immunotherapy are the model of the French Group of Immunotherapy and the Motzer model. With the arrivals of new molecular factors, these systems will perhaps have to evaluate: these new systems will require further validation as part of large prospective clinical trials.

The litterature dealing with the treatment of primary uretral carcinoma is very limited. Most of it is based on small series, case report or expert opinions. These guidelines are level IV. The treatment modality is mainly based on the lesion topography and not on the histology. For anterior T1 or 2 lesions, surgery is the most often used modality. In women, radiotherapy might be an attractive option. For more advanced lesions, the combination of radiotherapy and chemotherapy is the standard of care. The optimal protocol remains to be defined. Intradiverticular lesions in women are mainly adenocarcimoma. Surgery only is often inadequate.

Context.—Deletion of the short arm of chromosome 3 (3p deletion) is a cytogenetic abnormality generally associated with clear cell renal cell carcinoma, the most aggressive form of renal epithelial tumor. Objective.—To cytogenetically characterize 24 renal tumors in order to check the incidence and the type of 3p deletions, as well as to identify new genes putatively participating in renal tumorigenesis and test the protein products of the von Hippel-Lindau (VHL) and fragile histidine triad (FHIT) genes. Design.—We analyzed 24 renal tumors by conventional cytogenetics, comparative genomic hybridization, and fluorescence in situ hybridization. We then performed a comparative expression study of the proteins pVHL and Fhit. Results.—In our series of 24 renal tumors, the 3p deletion was the most frequent genetic alteration (15/24); the other features were partial trisomy 5q, 8p deletion, and monosomy 9 and 14. The 3p deletion was long and terminal, and no interstitial deletion was identified. By immunohistochemistry, we found that for the 2 genes of interest, VHL and FHIT, loss or decrease in protein expression were very frequently observed in clear cell renal cell carcinoma and not always associated with a 3p deletion (14/20 in clear cell renal cell carcinoma). Conclusions.—Our studies characterize the 3p deletion as long and terminal and identify no interstitial deletion in that chromosome. Fhit and pVHL protein expression loss appear to be independent, as they can be dissociated. Our data are supportive of a role for FHIT (in addition to VHL) in renal tumorigenesis. No other gene with particular potential interest in renal tumorigenesis could be identified among the selected genes.

A link between neuroendocrine cell differentiation and resistance to androgen deprivation has been observed in prostate cancer, suggesting the possible efficacy of specific treatments. We assessed the efficacy and toxicity of a chemotherapy regimen combining docetaxel and cisplatin in men with androgen independent prostatic adenocarcinoma and circulating neuroendocrine markers.A total of 41 patients were treated with a combination of 75 mg/m(2) docetaxel and 75 mg/m(2) cisplatin every 3 weeks for a maximum of 6 cycles. The primary study end point was the neuroendocrine response rate, defined as a decrease in neuron specific enolase and/or chromogranin A to 50% or greater of the supranormal baseline serum value. Median followup was 40 months.A median of 6 cycles per patient was delivered. A neuroendocrine response was observed in 13 patients (33%). The median response duration was 4 months (range 2 to 10). The prostate specific antigen response rate was 48%. A clinical benefit was observed in 45% of patients who required analgesics at study entry. The objective response rate was 41% in 29 patients with measurable metastases. Five patients had to stop therapy due to toxicity. The main side effects were cumulative asthenia and sensitive neuropathy. Median survival was 12 months (range 1 to 38).Regarding the disappointing efficacy and significant toxicity observed in this study, the combination of docetaxel and cisplatin cannot be recommended in daily practice. Further studies are necessary to determine whether patients with circulating neuroendocrine markers require specific therapeutic approaches.

Resume But Evaluer la morbidite du prelevement renal chez le donneur vivant (DV), les consequences medicales et l’impact sur la qualite de vie (QdV) a long terme. Materiel et methodes Analyse retrospective des donnees medico chirurgicales de 114 patients preleves dans un seul centre universitaire entre 1977 et 2005. La survenue de complications a ete evaluee par rapport a la voie d’abord chirurgicale et a l’indice de masse corporel (IMC) en utilisant le test du chi 2 ou le test exact de Fisher. Les evolutions de la fonction renale (creatininemie, clairance de la creatinine), de la proteinurie et de la pression arterielle (PA) ont ete etudiees par le test t de Student ou le test non parametrique U de Mann et Withney Wilcoxon. La QdV a long terme a ete evaluee par le questionnaire MOS SF-36 et par un questionnaire local puis comparee a celle de la population generale francaise. Resultats Le suivi median etait de 63 mois. La morbidite du prelevement etait significativement correlee a la voie d’abord (p=0,018) et a un IMC ≥ 25 kg/m2 (p=0,014). La mortalite etait nulle. Une elevation moderee de la creatininemie a ete enregistree au cours du suivi (creatininemie moyenne de 82,2μmol/1 [ +/- 16,3] a 104,5 [ +/-19,9]), ainsi qu’une baisse de la clairance (de 113,4 ml/min [+/- 27,6] a 76 [ +/- 29,9]). La proteinurie et la PA ont ete peu influencees. La QdV n’a pas ete alteree par le prelevement renal. Conclusion Le taux de complications peri operatoire est correle a l’IMC et a l’abord par lombotomie. Le prelevement renal reduit la filtration glomerulaire mais la clairance demeure stable durant le suivi. Une macro albuminurie ou une HTA peuvent apparaitre. Leur frequence n’est pas majoree par rapport a la population generale. La QdV des DV n’est pas alteree. Une information claire aupres du grand public permettrait la promotion de la transplantation a partir de DV.

OBJECTIVE To assess the clinical characteristics and outcome of patients with liver metastases in prostate carcinoma. PATIENTS AND METHODS From January 1995 to December 2005, 345 patients with metastatic prostate cancer were prospectively recorded in the database of the Montpellier Cancer Centre, France. The clinical characteristics and outcome of 28 patients who developed liver metastases during the course of the disease were analysed. RESULTS Six patients had liver metastases as the first site of metastatic disease, and for one of them, liver was the only metastatic site. All but one patient had hormone-refractory disease. Serum measurement of neuroendocrine markers showed increased levels of chromogranin A and neurone-specific enolase in 84% and 44% of patients, respectively. Six patients had a pathological analysis; there were two different histological patterns in liver biopsies, i.e. four were adenocarcinomas with a moderate (one patient) or poor (three) differentiation and two were neuroendocrine carcinomas. Three patients had no treatment because of a poor performance status. One patient had hormone therapy for synchronous liver metastases at diagnosis as the first-line treatment; other patients were treated with chemotherapy. The median (range) overall survival was 6 (1-27) months; the median survival of patients for whom liver was part of the initial metastatic pattern was 14 months. CONCLUSION Liver metastases are not very rare but appear to be a rather late event in the course of the disease. They are frequently associated with neuroendocrine characteristics.

International audience; BACKGROUND: Prostate cancer is the most common cancer in male in most Western countries, including France. Despite a significant morbidity and mortality to a lesser extent, the etiology of prostate cancer remains largely unknown. Indeed, the only well-established risk factors to date are age, ethnicity and a family history of prostate cancer. We present, here, the rationale and design of the EPIdemiological study of Prostate CAncer (EPICAP), a population-based case-control study specifically designed to investigate the role of environmental and genetic factors in prostate cancer. The EPICAP study will particularly focused on the role of circadian disruption, chronic inflammation, hormonal and metabolic factors in the occurrence of prostate cancer. METHODS/DESIGN: EPICAP is a population-based case-control study conducted in the département of Hérault in France. Eligible cases are all cases of prostate cancers newly diagnosed in 2012-2013 in men less than 75 years old and residing in the département of Hérault at the time of diagnosis. Controls are men of the same age as the cases and living in the département of Hérault, recruited in the general population.The sample will include a total of 1000 incident cases of prostate cancer and 1000 population-based controls over a 3-year period (2012-2014).The cases and controls are face-to-face interviewed using a standardized computed assisted questionnaire. The questions focus primarily on usual socio-demographic characteristics, personal and family medical history, lifestyle, leisure activities, residential and occupational history. Anthropometric measures and biological samples are also collected for cases and controls. DISCUSSION: The EPICAP study aims to answer key questions in prostate cancer etiology: (1) role of circadian disruption through the study of working hours, chronotype and duration/quality of sleep, (2) role of chronic inflammation and anti-inflammatory drugs, (3) role of hormonal and metabolic factors through a detailed questionnaire, (4) role of individual genetic susceptibility of genes involved in biological pathways of interest. The EPICAP study will also allow us to study prognostic factors and tumor aggressiveness.Taken together, the EPICAP study will provide a comprehensive framework to go further in the understanding of prostate cancer occurrence and its prognosis.

To determine the impact of renal graft nephrectomy on second kidney transplantation survival.We carried out a retrospective single-center study by analyzing cases performed from January 2000 to December 2011. Retransplanted patients who underwent previous allograft nephrectomy more than 3 months post-transplantation (group 1) were compared with those who did not (group 2) in terms of graft survival, incidences of acute rejection and delayed graft function. Multivariate Cox proportional hazard models were used to assess risk factors of graft loss after retransplantation.Overall, 146 patients were analyzed, including 52 (35.6%) in group 1 and 94 (64.4%) in group 2. Group 1 patients presented a significantly shorter first graft survival (0.8 vs 8.6 years, P 0.001) and more anti-class I antibodies (90.5% vs 74.2%, P = 0.03). A total of 10 patients (19%) in group 1 and 16 patients (17%) in group 2 had at least one acute rejection episode (P = 0.74). Delayed graft function was observed in 13 patients (25%) in group 1 and 17 patients (18%) in group 2 (P = 0.32). Graft survival at 1, 5 and 10 years was, respectively, 94%, 81% and 58% in group 1, and 99%, 93% and 66% in group 2 (P = 0.10). Graft survival was decreased by increased donor age and serum creatinine, and tended to be associated with post-transplantation presence of anti-class I and II antibodies. Graft nephrectomy was not associated with graft survival in multivariate analysis.Graft nephrectomy, probably a marker of high immunological risk patients, is not a risk factor of increased retransplant failure.

To quantify and compare cancer-specific mortality (CSM) and other-cause mortality (OCM) in individuals with stage T1G1-3 clinically node-negative (cN0) squamous cell carcinoma of the penis (SCCP) since there is no consensus regarding the need for an inguinal lymph node dissection (ILND) in patients with T1G2-3 cN0 SCCP.Relying on the Surveillance, Epidemiology and End Results database, we identified 655 patients diagnosed with primary SCCP between 1988 and 2006. Cumulative incidence plots were used to graphically depict the effect of CSM relative to OCM. Competing-risks regression analyses were used to quantify the risk of CSM or OCM after adjusting for age, race, tumour grade and surgery type.The 5-year CSM rates after a primary tumour excision without ILND were 2.6%, 10.0% and 15.9% in patients with respectively T1G1, T1G2 and T1G3 cN0 SCCP. The 5-year OCM rates were 29.5%, 27.3% and 29.3% in patients with respectively T1G1, T1G2 and T1G3. Age failed to provide additional stratification.The CSM rate was highest in T1G3 patients and appears to justify ILND. Conversely, the CSM rate was lowest in T1G1 patients, which justifies active surveillance in this patient subset. A moderate CSM rate at 5 years was recorded for T1G2 patients, which brings into question the benefits of ILND.

International audience; PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

To assess the safety and to obtain preliminary data on the efficacy of the three-drug combination chemotherapy with gemcitabine, oxaliplatin and vinorelbine in patients with metastatic bladder cancer.Patients with metastatic or locally unresectable advanced bladder cancer who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received intravenous gemcitabine 700 mg/m(2) and vinorelbine 25 mg/m(2) on day 1, then intravenous oxaliplatin 85 mg/m(2) on day 2, every 14 days.Fifteen patients were enrolled. Twelve patients were unfit for cisplatin. A median of five cycles per patient were delivered. The most common toxicities were neutropenia, nausea and vomiting, mucositis and diarrhoea. Two complete responses and one partial response were observed for an overall response rate of 23%. Median progression-free survival was 5.7 months and overall survival was 8.6 months.Although active and tolerable, the described three-drug combination chemotherapy showed no obvious incremental increase in efficacy compared with two-drug regimens. Further clinical trials are not recommended.

BACKGROUND: Conditional survival (CS) implies that, on average, long-term cancer survivors have a better prognosis than newly diagnosed individuals. The objective of the current study was to devise an accurate predictive tool that accounts for CS in men diagnosed with penile cancer. METHODS: Overall, 1245 patients treated with primary tumor excision (PTE) for pT1-3M0 squamous cell carcinoma of the penis (SCCP) between 1998 and 2006 were identified. Cox regression models were fitted for prediction of cancer-specific mortality (CSM). Nomogram development for prediction of CSM using CS methodology at 2 and 5 years was performed on 670 patients. External validation and calibration of the conditional nomogram was performed in 575 patients. RESULTS: The 5-year CSM-free survival of patients at surgery was 84.3% and increased to 95.0% and 97.8% after 2 and 5 years of disease-free survival (DFS), respectively. The predicted probabilities varied by as much as 49% (57% vs 85%) when, for example, predictions of CSM-free survival at 5 years were made after PTE versus after 2 years of DFS. Within the external validation cohort, the accuracy of the conditional nomogram was 75.3% and 78.1% at 2 and 5 years after PTE. CONCLUSIONS: The authors developed and externally validated the first conditional nomogram for predicting SCCP CSM-free survival that allows consideration of the length of survivorship. Cancer 2011;. © 2011 American Cancer Society.