[Impact of neoadjuvant chemotherapy on the peri-operative morbidity of radical cystectomy for muscle invasive bladder cancer]. / Impact de la chimiothérapie néoadjuvante sur la morbidité péri-opératoire de la cystectomie pour tumeur de vessie infiltrant le muscle.

INTRODUCTION: Platinum-based neoadjvant chemotherapy (NAC) before radical cystectomy (RC) is the gold standard in the treatment of muscle invasive bladder cancer (MIBC). We aimed to compare the peri-operative morbidity in patients treated by NAC then RC and patients having RC alone. METHODS: Between 1st January 2008 and 31st December 2015, we retrospectively included consecutive patients undergoing RC for MIBC in 2centers. We collected clinical, pathological and peri-operative data (30day post operative complications according to the Clavien-Dindo score, delayed complications, pathological results). Patients treated by NAC (NAC-RC group) before RC were compared to patients performing RC alone. The NAC-RC group received 1 to 6cycle of high-dose MVAC, MVAC or gemcitabine-cisplatine chemotherapy. Logistic regression identified independant factors of peri-operative complications. RESULTS: We included 199 patients: 48in the NAC-RC group and 151in the RC group. Complications rate was 73.9% in the NAC-RC group versus 73.8% in the RC group (P=1.0). In multivariate analyses, only the Charlson score was associated with an increased risk of peri-operative complications (P=0.05). PT0 tumour rate was significantly higher in the NAC-CR group (50% vs 7%, P<0.001). CONCLUSION: NAC does not increase the peri-operative morbidity of the RC. Patients' pre operative comorbidities is the main risk factor for peri-operative complications.

[Treatment of Urinary incontinence associated with genital prolapse: Clinical practrice guidelines]. / Traitement de l'incontinence urinaire associée au prolapsus génital : Recommandations pour la pratique clinique.

INTRODUCTION: Prolapse and urinary incontinence are frequently associated. Patente (or proven) stress urinary incontinence (SUI) is defined by a leakage of urine that occurs with coughing or Valsalva, in the absence of any prolapse reduction manipulation. Masked urinary incontinence results in leakage of urine occurring during reduction of prolapse during the clinical examination in a patient who does not describe incontinence symptoms at baseline. The purpose of this chapter is to consider on the issue of systematic support or not of urinary incontinence, patent or hidden, during the cure of pelvic organs prolapse by abdominal or vaginal approach. MATERIAL AND METHODS: This work is based on an systematic review of the literature (PubMed, Medline, Cochrane Library, Cochrane database of systematic reviews, EMBASE) for meta-analyzes, randomized trials, registries, literature reviews, controlled studies and major not controlled studies, published on the subject. Its implementation has followed the methodology of the HAS on the recommendations for clinical practice, with a scientific argument (with the level of evidence, NP) and a recommendation grade (A, B, C, and professional agreement). RESULTS: In case of patent IUE, concomitant treatment of prolapse and SUI reduces the risk of postoperative SUI. However, the isolated treatment of prolapse can treat up to 30% of preoperative SUI. Concomitant treatment of SUI exposed to a specific overactive bladder and dysuria morbidity. The presence of a hidden IUE represents a risk of postoperative SUI, but there is no clinical or urodynamic test to predict individually the risk of postoperative SUI. Moreover, the isolated treatment of prolapse can treat up to 60% of the masked SUI. Concomitant treatment of the hidden IUE therefore exposes again to overtreatment and a specific overactive bladder and dysuria morbidity. CONCLUSION: In case of overt or hidden urinary incontinence, concomitant treatment of SUI and prolapse reduces the risk of postoperative SUI but exposes to a specific overactive bladder and dysuria morbidity (NP3). The isolated treatment of prolapse often allows itself to treat preoperative SUI. We can suggest not to treat SUI (whether patent or hidden) at the same time, providing that women are informed of the possibility of 2 stages surgery (Grade C). © 2016 Published by Elsevier Masson SAS.

[Neoadjuvant chemotherapy in muscular invasive bladder cancer: Complications and consequences with cystectomy]. / Chimiothérapie néoadjuvante dans le cancer de vessie infiltrant le muscle : complications et conséquences sur la réalisation de la cystectomie.

INTRODUCTION: The fear of the deterioration of the patient's condition related to the toxicity of neoadjuvant chemotherapy is a barrier to its development. This multicenter retrospective study aims to present the secondary effects of neoadjuvant chemotherapy and its impact on the achievement of cystectomy. MATERIALS AND METHODS: Patients with urothelial carcinoma classified cT2 to cT4a N0M0 were included. Chemotherapy with 6 cycles of MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) followed by a cysto-prostatectomy or anterior pelvectomy was scheduled. RESULTS: A total 32 patients were included. Six cycles of neoadjuvant chemotherapy were performed in all 11 patients. Shutdown causes were toxicity in 85% of cases. Cystectomy was performed in 86.6% of patients. Surgery was not performed in 6 patients. The reasons were the alteration of the general condition in 2 cases, 2 patients had advanced cancers diagnosed intraoperatively, and 2 refused surgery. Complications of grades 3 and 4 according to the classification of Clavien and Dindo had occurred respectively in 15.3% and 11.5%. DISCUSSION: This study reports results close to what is found in the literature on the effects of neoadjuvant chemotherapy on achieving cystectomy, but it has some limitations: the retrospective analysis of data on surgery and the lack of control group. In addition, the short follow-up does not yet allow to know the long-term oncological results. CONCLUSION: This study supports the fact that the toxicity of neoadjuvant chemotherapy does not seem to cause a significant risk of non-completion of cystectomy. LEVEL OF EVIDENCE: 4.

[Qualitative and quantitative hormonal regulation in castration-resistant prostate cancer]. / Régulation hormonale qualitative et quantitative dans le cancer de la prostate résistant à la castration.

INTRODUCTION: Despite initial sensitivity to androgen deprivation, most metastatic prostate cancer patients will experience recurrence or progression. This evolution, which occurs while seric testosterone level is low, is called castration resistant prostate cancer (CRPC). MATERIAL AND METHODS: MEDLINE database was requested for French or English articles published until September 2012 responding to the following keywords: "castration resistant", "prostatic neoplasms", "androgens", "testosterone", "regulat*". Here is a summary of relevant data concerning both qualitative and quantitative hormonal regulation. RESULTS: androgen blood testing is not related to tissue concentrations, as prostate cancer cells exhibit higher hormones levels. Despite its higher biological efficiency, dihydrotestosterone is not the only mediator of androgen-dependent transcription. Androgen synthesis implies many pathways including lot of alternative ones. Steroïdogenesis can occur out of the testicles and the adrenals, and maybe in tumor cell or tissue. Major and minor androgens levels, as those of co-repressors and activators inside the tumor cell leads to a smooth androgen activity modulation. Many drugs have the ability to block those different steps. CONCLUSION: Castration resistance reflects an androgen activity in tumor cells while major androgen pathway activators are lowered. Alternate pathway include steroids pumps, de novo synthesis by tumor cells or their environment, minor androgens activation by co-factors regulation. Many drugs are known to inhibit those escaping ways. Nowadays they are not efficient enough, because of other minor pathways becoming dominant. Investigations are required but would need new detection techniques of low androgen concentrations in blood as in tissues.

[Choice of new drugs in castration-resistant prostate cancer: predictive factors and effectiveness assessment]. / Choix des nouveaux traitements médicaux dans le cancer de la prostate résistant à la castration: marqueurs prédictifs et évaluation de l'efficacité.

INTRODUCTION: Docetaxel has been the cornerstone in the treatment of castration- resistant prostate cancer (CRPC) since 2004. The recent and almost simultaneous arrival of new and effective molecules - several of which are already available on the market - has added to the CRPC treatment arsenal. Several studies have explored the optimal order in which these new treatments should be administered. The aim of this review was to present their respective predictive and evaluative factors and suggest potential administration sequences. METHODS: The PubMed medical literature citations database was searched using the following key words: prostate cancer, castration resistant, metastatic, targeted therapy, treatment sequence, immunotherapy and clinical trials. The reports of the most recent European and North American congresses were also included. RESULTS: While no predictive factors have been clearly identified for these new therapies to date, a Gleason score of not less than 8 and one or more chemotherapy sessions seemed to be predictive of lower efficacy for abiraterone. Promising elements for further investigation include the circulating tumour cell count and variation in this count per treatment, ERG mutation status or the intratumoural androgen status. Substitution criteria have not yet been reported but, as is the case with all hormone therapies, changes in PSA levels emerge as a valuable indicator of the efficacy of abiraterone. The best treatment sequence for patients who develop castration-resistance remains to be defined. CONCLUSION: Although new molecules have recently become available, the experience with their use is limited. Thus, no predictive markers of response rates and treatment outcomes or data concerning the best treatment sequence to use in patients with CRPC are as yet available.