Les nouveaux profils moléculaires dans le cancer de l’ovaire peuvent-ils modifier les stratégies thérapeutiques ?

National audienceEpithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine

Does uncontrolled cardiac death for organ donation raise ethical questions? An opinion survey.

International audienceBACKGROUND: Organ donation after uncontrolled cardiac death raises complex ethical issues. We conducted a survey in a large hospital staff population, including caregivers and administrators, to determine their ethical viewpoints regarding organ donation after uncontrolled cardiac death.METHODS: Multicenter observational survey using a questionnaire, including information on the practical modalities of the procedure. Respondents were asked to answer 15 detailed ethical questions corresponding to different ethical issues raised in the literature. Ethical concerns was defined when respondents expressed ethical concerns in their answers to at least three of nine specifically selected ethical questions.RESULTS: One thousand one hundred ninety-six questionnaires were received, and 1057 could be analysed. According to our definition, 573 respondents out of 1057 (54%) had ethical concerns with regard to donation after cardiac death and 484 (46 %) had no ethical concerns. Physicians (55%) and particularly junior intensivists (65%) tended to have more ethical issues than nurses (52%) and hospital managers (37%). Junior intensivists had more ethical issues than senior intensivists (59%), emergency room physicians (46%) and transplant specialists (43%).CONCLUSION: Only 46% of hospital-based caregivers and managers appear to accept easily the legitimacy of organ donation after cardiac death. A significant number of respondents especially intensivists, expressed concerns over the dilemma between the interests of the individual and those of society. These results underline the need to better inform both healthcare professionals and the general population to help to the development of such procedure.2013 The Acta Anaesthesiologica Scandinavica Foundation

Risk factors for stress urinary incontinence recurrence after midurethral sling revision

International audienceObjectivesThe purpose of this study was to report the rate of stress urinary incontinence (SUI) recurrence after sling revision, and to determine predictive factors of SUI recurrence.MethodsWe conducted a retrospective cohort study in a single academic center between 2005 and 2022, of patients who underwent sling revision. Four surgical techniques were used for sling revision (loosening, section, partial, and total excision). The primary endpoint was recurrence of SUI at 3 months postoperatively, and the other outcome of interest was the rate of subsequent anti-incontinence surgical procedure.ResultsSixty-nine patients were included for analysis. SUI recurred in 46.4% of patients. Fifteen patients underwent a subsequent anti-incontinence procedure (21.8%). The time to revision was significantly longer in the group with recurrent SUI (median: 84.5 vs. 44.8 months; p = 0.004). The recurrence rate differed significantly depending on the revision technique: 7.7% after sling loosening, 22.2% after sling section, 60% after partial excision, and 66.7% after complete sling removal (p = 0.001). The risk of SUI recurrence was lower for those whose indication of reoperation was voiding dysfunction (27.3% vs. 66.7%; p = 0.002), and was higher for those who underwent a trans-obturator tap rather than a tension-free vaginal tape revision (68.4% vs. 35.7%; p = 0.02). In multivariate analysis, only the revision technique remained significantly associated with the risk of recurrence of SUI (complete excision vs. section: odds ratio = 4.66; p = 0.04).ConclusionThe risk of SUI recurrence may differ widely according to the techniques used, and it seems that the less extensive the surgical procedure is, the lower the risk is

Comparison of early loosening vs delayed section of mid-urethral slings for postoperative voiding dysfunction

International audienceIntroduction and hypothesis: Bladder outlet obstruction (BOO) is a common occurrence after midurethral sling (MUS) insertion and can result in acute or chronic urinary retention or de novo lower urinary tract symptoms (LUTS). However, the management of BOO after MUS is not standardised. The objective of this study was to compare two therapeutic strategies for suspected BOO after MUS. Methods: Patients who had surgical revision for voiding dysfunction with a post-void residual (PVR) ≥100 ml after MUS in five centres between 2005 and 2020 were included in a retrospective study. Patients were divided into two groups: early sling loosening (EL) vs delayed section/excision of the sling (DS). Results: Seventy patients were included: 38 in the EL group and 32 in the DS group. The postoperative complication rate was comparable in both groups (10.5% vs 12.5%; p = 0.99). At 3 months, the rate of withdrawal from self-catheterisation was similar in the two groups (92.1% vs 100%; p = 0.25) as was the PVR (57.5 vs 63.5 ml; p = 0.09). After a median follow-up of 9 months, there were significantly more patients with resolved voiding dysfunction in the EL group (63.2% vs 31.3%; p = 0.01). The rate of persistent/recurrent stress urinary incontinence (SUI) was higher in the DS group (21% vs 43.7%; p = 0.04). In multivariate analysis, the main predictive factor of recurrent SUI was DS (OR 2.87, 95% CI 1.01–8.60, p = 0.048). Conclusions: Early loosening of MUS in the case of postoperative voiding dysfunction offers better efficacy than DS of the sling, with a lower risk of recurrent/persistent SUI

Anatomic and functional mapping of human uterine innervation

International audienceOBJECTIVE: To better understand the physiology of pain in pelvic pain pathological conditions, such as endometriosis, in which alterations of uterine innervation have been highlighted, we performed an anatomic and functional mapping of the macro- and microinnervation of the human uterus. Our aim was to provide a 3-dimensional reconstruction model of uterine innervation. DESIGN: This was an experimental study. We dissected the pelvises of 4 human female fetuses into serial sections, and treated them with hematoxylin and eosin staining before immunostaining. SETTING: Academic Research Unit. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Detection of nerves (S100 +) and characterization of the types of nerves. The slices obtained were aligned to construct a 3-dimensional model. RESULTS: A 3-dimensional model of uterine innervation was constructed. The nerve fibers appeared to have a centripetal path from the uterine serosa to the endometrium. Within the myometrium, innervation was dense. Endometrial innervation was sparse but present in the functional layer of the endometrium. Overall innervation was richest in the supravaginal cervix and rarer in the body of the uterus. Innervation was rich particularly laterally to the cervix next to the parametrium and paracervix. Four types of nerve fibers were identified: autonomic sympathetic (TH+), parasympathetic (VIP+), and sensitive (NPY+, CGRP1+ and VIP+). They were found in the 3 portions and the 3 layers of the uterus. CONCLUSIONS: We constructed a 3-dimensional model of the human uterine innervation. This model could provide a solid base for studying uterine innervation in pathologic situations, in order to find new therapeutic approaches

Risk Factors of Post-Large Loop Excision of the Transformation Zone Recurrent High-Grade Cervical Intraepithelial Lesion

International audienceOBJECTIVE:The aim of the study was to identify the risk factors of post-large loop excision of the transformation zone (LLETZ) recurrent disease and the impact of colposcopic guidance at the time of LLETZ on that risk.MATERIALS AND METHODS:From December 2013 to July 2014, 204 patients who had undergone LLETZ for the treatment of high-grade intraepithelial lesion with fully visible cervical squamocolumnar junction were included. The use of colposcopy during each procedure was systematically documented. The dimensions and volume of LLETZ specimens were measured at the time of the procedure before formaldehyde fixation. All participants were invited for a follow-up. The primary endpoint was the diagnosis of post-LLETZ recurrent disease defined as the histologic diagnosis of a high-grade cervical intraepithelial lesion.RESULTS:The median duration of post-LLETZ follow-up was 25.8 months. Recurrent disease was diagnosed in 8 (3.6%) patients. Older than 38 years (adjusted hazard ratio [aHR] = 11.9, 95% CI = 1.6-86.0), history of excisional therapy (aHR = 21.6, 95% CI = 3.5-135.3), and the absence of colposcopy for the guidance of LLETZ (aHR = 6.4, 95% CI = 1.1-37.7) were found to significantly increase the risk of post-LLETZ recurrent disease. The dimensions and volume of the specimen were not found to have any impact. Only positive endocervical margins were identified to significantly increase the risk of post-LLETZ recurrent disease (aHR = 14.4, 95% CI = 2.0-101.1).CONCLUSIONS:Risk factors of post-LLETZ recurrent disease are older than 38 years, history of excisional therapy, positive endocervical margins, and lack of colposcopic guidance at the time of LLETZ

Vibrational Properties of CuO and Cu4O3 from First-Principles Calculations, and Raman and Infrared Spectroscopy

International audienceA combined experimental and theoretical study is reported on the vibrational properties of tenorite CuO and paramelaconite Cu4O3. The optically active modes have been measured by Raman scattering and infrared absorption spectroscopy. First-principles calculations have been carried out with the LDA+U approach to account for strong electron correlation in the copper oxides. The vibrational properties have been computed ab initio using the so-called direct method. Excellent agreement is found between the measured Raman and infrared peak positions and the calculated phonon frequencies at the Brillouin zone center, which allows the assignment of all prominent peaks of the Cu4O3 spectra. Through a detailed analysis of the displacement eigenvectors, it is shown that a close relationship exists between the Raman modes of CuO and Cu4O3