"Hormone-refractory" prostate cancer : a putative new mechanism: the upside-down response to androgens

En aquest article volem revisar la diversitat dels mecanismes moleculars suposadament responsables del creixement independent d'andrògens del càncer de pròstata. Es demostra que alguns càncers de pròstata que escapen de la teràpia endocrinològica estan compostos per cèllules sensibles als andrògens. Ens centraremen els resultats del nostre laboratori i en els d'altres grups de recerca que suggereixen el mateix concepte nou: el comportament del càncer de pròstata refractari als andrògens està associat a una resposta invertida de les cèll. ules als andrògens. Hem observat un alentiment paradoxal en el creixement de diverses línies cell. ulars induït pels andrògens. Aquestes línies cell. ulars provenen de les cèll. ules LNCaP, ja sigui per evolució espontània o per cultiu crònic en un medi sense andrògens. La línia ARCaP (androgen-reverted carcinoma of the prostate) va ser establerta a partir de l'ascitis d'un pacient amb càncer de pròstata avançat. Els tumors que varen créixer a partir d'aquestes cèll. ules reverteixen, encara que transitòriament, en el tractament androgènic. Volem suggerir que la castració podria permetre la proliferació de les cèll. ules que eren paradoxalment alentides pels andrògens i que aquesta reacció invertida als andrògens podria ser el possible mecanisme pel qual el càncer de pròstata deixa de respondre a la teràpia hormonal. Aquests resultats aportarien unes bases racionals per a comprendre el tractament antiandrogènic intermitent.In this paper we survey the diversity of the molecular mechanisms suspected to be responsible for the androgen-independent growth of prostate cancer. It has been shown that some prostate cancers, which escape endocrine therapy, are composed of androgen-sensitive cells. We focus on the results from our laboratory and from a few others that suggest a new concept: that the androgen-refractory behavior of prostate cancer may be associated with an inverted response to androgens by cells. The proliferation of several cell lines was paradoxically slowed by androgens. In the afore-mentioned studies, a series of these cell lines arose from the LNCaP cell line, either spontaneously or after culturing them chronically in androgen-poor culture medium. The ARCaP (androgen-reverted carcinoma of the prostate) was established from the ascites of a patient with advanced prostate cancer. Usually, tumors grown from such cells regress, albeit transiently, under androgen treatment. It has been suggested that castration could allow the proliferation of cells that are paradoxically slowed by androgens and that the inverted response to androgens could possibly be a mechanism, by which prostate cancer escapes from endocrine therapy. These results provide the rationale for intermittent treatment

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Programming settings and recharge interval in a prospective study of a rechargeable sacral neuromodulation system for the treatment of overactive bladder

Aims: The RELAX-OAB study is designed to confirm the safety, efficacy, and technical performance of the Axonics r-SNM System, a miniaturized, rechargeable SNM system approved in Europe and Canada for the treatment of bladder and bowel dysfunction. The purpose of this article is to describe study subjects’ ability to charge the rechargeable neurostimulator and to document their neurostimulator program settings and recharge interval over time. Methods: Fifty-one OAB patients were implanted in a single-stage procedure. These results represent the 3-month charging experience for 48 subjects who completed the 3-month follow-up. Recharge intervals were estimated using therapy stimulation settings and subject experience was evaluated using questionnaires. Results: Forty-seven of forty-eight (98%) subjects were able to successfully charge their device prior to follow-up within 1-month post-implant. At 3-month post-implant, 98% of subjects were able to charge prior to their follow-up visit. Average stimulation amplitude across all subjects was 1.8 mA (±1.1 mA). A total of 69% of subjects had ≥14-day recharge intervals (time between charging) and 98% of subjects had ≥7-day recharge interval. No charging related adverse events occurred. Conclusions: Study subjects were able to charge the Axonics r-SNM System and stimulation settings provided 2 weeks of therapy between recharging for most subjects. Subject satisfaction indicates that subjects are satisfied with rechargeable SNM therapy

PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision

Positive psychology and education, contributions to better prevention of violent radicalization : integrative socio-clinical diagnosis of violent radicalization and models of prevention that can be mobilized in positive psychology and positive education : lessons for future education

Depuis le début du XXIe siècle, des phénomènes d’extrémismes et de radicalisations violentes ont impacté un nombre important d’adolescents et de jeunes adultes à travers le monde. La question se pose donc de la prévention de ces phénomènes. C'est de cette prévention dont il s'agit dans la thèse ici présentée qui part du constat que, dans ce domaine, une institution et/ou un acteur socio-éducatif souhaitant s’engager dans la prévention primaire et secondaire des radicalisations violentes, inspirées par le jihadisme ne sait littéralement pas à quel saint se vouer : entre l’ignorance de nouvelles ressources éducatives disponibles non spécifiques qui ont fait leurs preuves, la quasi absence d’un diagnostic complet sur les facteurs de risque, d’évaluation d’impact des dispositifs mise en place qui ont parfois uniquement renforcé ce que nous savions déjà faire et de vrais recherches sur les facteurs de protection, rien ne semble, ou presque, éclairer la lanterne des bonnes volontés qui se présentent sur ce terrain parfois miné politiquement et médiatiquement.Comment améliorer cette prévention à partir de ressources éducatives innovantes ? La recherche ici présentée propose l’éducation positive et spirituelle comme possible voie pour prévenir plus efficacement les phénomènes d’extrémismes et de radicalisations violentes. L’objectif, modeste et ambitieux, est d’avancer ce qui paraît légitime comme ressources, à titre d’exemples probants mais aussi à titre exploratoire, à la fois pour corroborer des facteurs de risque et de protection et pour inspirer de nouvelles pratiques innovantes et évaluées pour les futurs de l’éducation, à la fois dans la prévention des violences mais surtout plus globalement pour en tirer les leçons pour une éducation dynamique à la paix et au leadership éclairé.Since the beginning of the 21st century, phenomena of extremism and violent radicalization have impacted a significant number of adolescents and young adults around the world. The question therefore arises of the prevention of these phenomena. It is this prevention that is concerned in the thesis presented here, which starts from the observation that, in this field, an institution and /or a socio-educational actor wishing to engage in the primary and secondary prevention of violent radicalizations, inspired by jihadism, literally does not know which way to turn : between the ignorance of new available non-specific educational resources that have proven their worth, the virtual absence of a complete diagnosis of risk factors, of evaluation of impact of the measures put in place which have sometimes only reinforced what we already knew how to do and real research on protective factors, nothing seems, or almost, to shed light on the lantern of the goodwill that presents itself in this field which is sometimes politically undermined and mediatically.How to improve this prevention using innovative educational resources?The research presented here proposes positive and spiritual education as a possible way to prevent more effectively the phenomena of extremism and violent radicalization. The goal, modest and ambitious, is to put forward what seems legitimate as resources, as convincing examples but also on an exploratory basis, both to corroborate risk and protective factors and to inspire new innovative practices and evaluated for the future of education, both in the prevention of violence but above all more generally to draw lessons for a dynamic education in peace and enlightened leadership

Cancer de la prostate et biopsie (signification carcinologique d'un prélèvement positif sur douze)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Destruction chimique des racines sacrées par injection d'alcool en traitement de l'hyperactivité vésicale

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Interactions entre hormones, multiplication cellulaire et apoptose dans la prostate

LYON1-BU Santé (693882101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Utilisation du sphincter urinaire artificiel AMS 800 périprostatique pour le traitement de l'incontinence urinaire par insuffisance sphincterienne neurologique (étude multicentrique rétrospective - à propos de 51 cas)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF