Bandelette sous-urétrale itérative pour récidive d incontinence urinaire d effort féminine

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer

Background: We aimed to provide a comprehensive literature review on the best practice management of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) using neoadjuvant chemotherapy (NAC). Method: Between July and September 2018, we conducted a systematic review using MEDLINE and EMBASE electronic bibliographic databases. The search strategy included the following terms: Neoadjuvant Therapy and Urinary Bladder Neoplasms. Results: There is no benefit of a single-agent platinum-based chemotherapy. Platinum-based NAC is the gold standard therapy and mainly consists of a combination of cisplatin, vinblastine, methotrexate, doxorubicin, gemcitabine or even epirubicin (MVAC). At 5 years, the absolute overall survival benefit of MVAC was 5% and the absolute disease-free survival was improved by 9%. This effect was observed independently of the type of local treatment and did not vary between subgroups of patients. Moreover, a ypT0 stage (complete pathological response) after radical cystectomy was a surrogate marker for improved oncological outcomes. High-density MVAC has been shown to decrease toxicity (with a grade 3–4 toxicity ranging from 0% to 26%) without impacting oncological outcomes. To date, there is no role for carboplatin administration in the neoadjuvant setting in patients that are unfit for cisplatin-based NAC administration. So far, there is no published trial evaluating the role of immunotherapy in a neoadjuvant setting, but many promising studies are ongoing. Conclusion: There is a strong level of evidence supporting the clinical use of a high-dose-intensity combination of methotrexate, vinblastine, doxorubicin and cisplatin in a neoadjuvant setting. The landscape of MIBC therapies should evolve in the near future with emerging immunotherapies

New immunotherapy treatments in non-muscle invasive bladder cancer

: Non-muscle invasive bladder cancer (NMIBC) is a highly heterogeneous disease that hides classes of patients who behave significantly differently under a favorable overall prognosis facade. Individual risk stratification and good decision making improve the patient outcomes. To date, radical cystectomy remains the treatment of choice in particularly aggressive subsets of disease, also due to the lack of proven alternative bladder-sparing strategies.Cancer immunotherapy, by inhibiting the PD-1/PD-L1axis, has shown durable efficacy in the treatment of advanced and metastatic unresectable urothelial carcinoma, and is studied with great interest in early disease settings. The updated data of the KEYNOTE-057 study have recently promoted the United States (US) Food and Drug Administration (FDA) approval of pembrolizumabin patients with CIS-containing BCG-unresponsive NMIBC. This significant step forward paves the way to a new window of therapeutic opportunities, while underlining new needs and questions to be addressed

Is it worth starting sexual rehabilitation before radical prostatectomy? Results from a systematic review of the literature

Background and Purpose: Sexual dysfunction (SD) is a frequent side effect associated with radical prostatectomy (RP) for prostate cancer (PCa). Some studies have showed the benefit associated with preoperative sexual rehabilitation (prehabilitation) and Enhanced Recovery After Surgery (ERAS) for RP, but no clear clinical recommendations are available yet. Our aim was to conduct a systematic review on sexual prehabilitation prior to RP for patients with a localized PCa and analyze the impact on postoperative sexual health compared with the standard post-operative care. Methods: We performed a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) recommendations. Results: Four randomized control trials and one retrospective comparative study were included in the analyses. Three of the five studies showed an improved EF recovery post-RP in the prehabilitation group compared to the standard of care represented by: higher International Index of Erectile Function 5 score (IIEF5) or IIEF score (p < 0.0001) and a higher percentage of patients reporting return of EF based on the Sexual Encounter Profile (SEP) (56 vs. 24%, p = 0.007). Self-confidence, therapeutic alliance, and adherence to treatment were stronger for patients with preoperative consultations (p < 0.05) and EF recovery was better in cases of a higher number of follow-up visits (OR 4–5 visits vs. 1:12.19, p = 0.002). Discussion: Despite heterogenous methods and high risks of bias in this systematic review, starting sexual rehabilitation prior to surgery seems to ensure better EF recovery. This prehabilitation should include information of both the patient and his or her partner, with a closer follow up and the use of a multimodal treatment approach that still remains to be defined and validated (oral medication, vacuum devices, pelvic floor muscle training, etc.)

Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art

: Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal-papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC

Efficacy, Safety, and Reoperation-free Survival of Artificial Urinary Sphincter in Non-neurological Male Patients over 75 Years of Age

Background: Artificial urinary sphincter (AUS) is a gold standard treatment in male stress urinary incontinence but remains poorly used in elderly patients. Objective: To assess the efficacy, safety, and reoperation-free survival of AUS implantation in male patients over 75 yr of age. Design, setting, and participants: We retrospectively reviewed the charts of all 1233 non-neurological male AUS implantations between 2005 and 2020 at 13 French centers. We compared 330 patients ≥75 yr old (GROUP75+) with 903 patients <75 yr old (GROUP75–) at the time of AUS implantation. Outcome measurements and statistical analysis: Our primary endpoint was social continence at 3 mo defined as the use of one or fewer pad daily. We used Kaplan-Meier analyses to assess reoperation-free survival. We sought factors of erosion using logistic regression. Results and limitations: Early postoperative continence was comparable in both groups (74.4% vs 80.1%, p = 0.114). We observed a higher rate of postoperative complications in GROUP75+ (18.8% vs 12.6%, p = 0.014), but the complications were more frequently of low grade in GROUP75+ (p = 0.025). The overall reoperation-free survival was similar (p = 0.076) after a median follow-up of 2 yr. However, patients in GROUP75+ had poorer explantation-free survival (p < 0.0001). A history of radiotherapy was a predictive factor of erosion (odds ratio [OR] = 5.31, p < 0.01), but age was not (OR = 1.08, p = 0.87). Unfortunately, our dataset did not include a systematic geriatric evaluation. Conclusions: AUS in elderly patients appears to be an effective option to treat stress urinary incontinence. However, we observed more postoperative complications and explantations, although age was not associated with the onset of erosion. A prospective study is required to determine whether a geriatric evaluation would be an effective strategy to select patients before surgery. Patient summary: In this study, we looked at outcomes of artificial urinary sphincter in elderly men in a large population. We found satisfying efficacy but slightly more postoperative complications and device infections

Transcriptomic Profiling of Upper Tract Urothelial Carcinoma: Bladder Cancer Consensus Classification Relevance, Molecular Heterogeneity, and Differential Immune Signatures

International audienceAnalyses of large transcriptomics data sets of muscle-invasive bladder cancer (MIBC) have led to a consensus classification. Molecular subtypes of upper tract urothelial carcinomas (UTUCs) are less known. Our objective was to determine the relevance of the consensus classification in UTUCs by characterizing a novel cohort of surgically treated ≥pT1 tumors. Using immunohistochemistry (IHC), subtype markers GATA3-CK5/6-TUBB2B in multiplex, CK20, p16, Ki67, mismatch repair system proteins, and PD-L1 were evaluated. Heterogeneity was assessed morphologically and/or with subtype IHC. FGFR3 mutations were identified by pyrosequencing. We performed 3'RNA sequencing of each tumor, with multisampling in heterogeneous cases. Consensus classes, unsupervised groups, and microenvironment cell abundance were determined using gene expression. Most of the 66 patients were men (77.3%), with pT1 (n = 23, 34.8%) or pT2-4 stage UTUC (n = 43, 65.2%). FGFR3 mutations and mismatch repair-deficient status were identified in 40% and 4.7% of cases, respectively. Consensus subtypes robustly classified UTUCs and reflected intrinsic subgroups. All pT1 tumors were classified as luminal papillary (LumP). Combining our consensus classification results with those of previously published UTUC cohorts, LumP tumors represented 57.2% of ≥pT2 UTUCs, which was significantly higher than MIBCs. Ten patients (15.2%) harbored areas of distinct subtypes. Consensus classes were associated with FGFR3 mutations, stage, morphology, and IHC. The majority of LumP tumors were characterized by low immune infiltration and PD-L1 expression, in particular, if FGFR3 mutated. Our study shows that MIBC consensus classification robustly classified UTUCs and highlighted intratumoral molecular heterogeneity. The proportion of LumP was significantly higher in UTUCs than in MIBCs. Most LumP tumors showed low immune infiltration and PD-L1 expression and high proportion of FGFR3 mutations. These findings suggest differential response to novel therapies between patients with UTUC and those with MIBC. Copyrigh

Impact of prior antibiotic therapy on severe necrotizing soft-tissue infections in ICU patients: results from a French retrospective and observational study

International audienceAbstract Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively ( p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable ( n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings

Various Genital and Reproductive Phenotypes in 46,XX/46,XY Chimeras

International audienceTetragametic chimeras are due to the fusion of 2 different zygotes after fertilization. When occurring between embryos of different chromosomal sex, the phenotype ranges from fertile individuals to infertile patients and even to patients with variations in sex development. Here, we report 3 new cases of XX/XY chimeras, one in a young boy carrying an abnormal gonad which turned out to be an ovary and 2 in phenotypically normal infertile men, one of whom had been diagnosed previously as a XX-SRY negative male. These cases highlight the importance of combining several cytogenetic and molecular techniques on different tissues for a proper diagnosis and an appropriate prognosis