Détermination sur tissu endométrial néoplasique de profils d'expression de micro-ARNs associés à l'envahissement ganglionnaire dans le cancer de l'endomètre de type endométrioïde de stade précoce

Current histological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely predict lymph node metastases leading to potential over or under treatment. Hence, additional highly sensitive and specific molecular prognostic biomarkers correlated with prognostic factors, such as nodal involvement and lymphovascular space involvement (LVSI), are needed to better adapt surgical management and adjuvant therapies. We fstudied by microarray analysis microRNA expression profiles of formalin-fixed paraffin-embedded grade 1–2 supposed early-stage endometrioid adenocarcinomas specimen. The expression levels of 5 microRNAs (miR-34c-5p, -375, -184, -34c-3p, et -34b-5p) were lower in the EC with positive nodal status compared to those with negative nodal status. The expression levels of 3 microRNAs (miR-34c-5p, -23b-5p, et -23c) were lower in the EC with positive LVSI compared to those with negative LVSI. A quantitative reverse transcriptase–PCR assay was used to determine micro-RNAs thresholds correlated with prognostic factors. Women with a microRNA-184-fold change 0.30 (n=3; 11.5%), p=0.006. Women with a microRNA-34c-5p fold change 0.15 (n=0; 0.0%), p0,30, p=0,006. Les patientes avec seuil d'expression du micro-ARN-34c-5p 0,15 (0,0%), p<0,001. Ces profils d'expression de micro-ARNs fournissent les bases pour de nouvelles études sur la fonction des micro-ARNs dans le cancer de l'endomètre et pourraient constituer un nouvel outil au diagnostic du statut ganglionnaire

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1-2 endometrial cancer

La classification du cancer de l'endomètre, basée sur l'histologie, conditionne la prise en charge thérapeutique alors qu'elle ne montre pas une pertinence suffisante pour prédire l'envahissement ganglionnaire. La détermination de profils d'expression biologiques corrélés au statut ganglionnaire et à d'autres facteurs pronostiques majeurs tels que les emboles apparait donc fondamentale pour mieux adapter la prise en charge. Nous avons montré, par une analyse de puce à partir des ARNs extraits de tissus sous paraffine de cancer de l'endomètre de type endométrioide, de grade 1-2, supposé limité à l'utérus, que les niveaux d'expression de cinq micro-ARNs (miR-34c-5p, -375, -184, -34c-3p, et -34b-5p) étaient plus faibles dans les tissus tumoraux avec envahissement ganglionnaire. Les niveaux d'expression de trois micro-ARNs (miR-34c-5p, -23b-5p, et -23c) étaient plus faibles dans les tissus tumoraux avec emboles lymphovasculaires. Une analyse par RT-qPCR a permis de déterminer des seuils de micro-ARNs corrélés aux facteurs pronostiques. Les patientes avec seuil d'expression du micro-ARN-184 0,30, p=0,006. Les patientes avec seuil d'expression du micro-ARN-34c-5p 0,15 (0,0%), p0.30 (n=3; 11.5%), p=0.006. Women with a microRNA-34c-5p fold change 0.15 (n=0; 0.0%), p<0.001. These microRNA expression profiles may provide a basis for further studies of the micro-RNA function in endometrioid adenocarcinoma, and be used as a diagnostic tool

Complications vasculo-placentaires chez les femmes enceintes infectées par le VIH : une étude cas-témoin

Background: Data from international literature suggest a link between HIV infection and placental vascular complications during pregnancy. Current studies on the subject are conflicting.Objective: The aim of the study was to evaluate the incidence of placental vascular complications during pregnancy among HIV+ and HIV- patients.Study Design: It is a single-center case-control study comparing the rates of gestational hypertension, preeclampsia, eclampsia and vascular intrauterine growth retardation from 280 HIV+ and 560 HIV- patients matched by age, parity and geographical origin.Results: The rate of placental vascular complications was not statistically different between HIV+ and HIV- patients: 7.5% vs 9.8%, respectively (p = 0.27). HIV+ patients have a significant increase in overall prematurity rate: 18.6% vs 8.0%, p <0.0001 and a significant decrease in birthweight for gestational age: 41.6th percentile vs 46.6th percentile, p = 0.02.Conclusion: This study does not observe difference in the incidence of placental vascular complications between HIV + and HIV- patients. The significant increase in prematurity and low birth weight among HIV + patients has to be explored by further specific studies.Introduction : Les données de la littérature internationale laissent penser qu’il existe un lien entre l’infection VIH et les complications vasculo-placentaires pendant la grossesse. Les études actuelles sur le sujet sont discordantes.Objectif : Le but de l’étude est d’évaluer l’incidence des complications vasculo-placentaires pendant la grossesse entre des patientes VIH+ et des patientes VIH-.Matériel et Méthode : Il s’agit d’une étude cas-témoin monocentrique comparant les taux d’hypertension artérielle gravidique, de prééclampsie, d’éclampsie et de retard de croissance intra utérin vasculaire entre 280 patientes VIH+ et 560 patientes VIH- appariées selon l’âge, la parité et l’origine géographique.Résultats : Le taux de complications vasculo-placentaires n’est pas statistiquement différent entre les patientes VIH+ et VIH- : 7,5% vs 9,8% respectivement (p= 0,27). Les patientes VIH+ ont une augmentation significative des taux de prématurité globale : 18,6% vs 8,0%, p<0,0001 et une diminution significative des poids de naissance pour l’âge gestationnel : 41,6ème percentile vs 46,6ème percentile, p=0,02.Conclusion : Cette étude ne permet pas d’observer de différence d’incidence de complication vasculo-placentaire entre des patientes VIH+ et VIH-. L’augmentation significative de la prématurité et des petits poids de naissance chez les patientes VIH+ est à explorer par des études complémentaires spécifiques

Fertility-Sparing Surgery for Ovarian Cancer

International audience(1) Background: although most patients with epithelial ovarian cancer (EOC) undergo radical surgery, patients with early-stage disease, borderline ovarian tumor (BOT) or a non-epithelial tumor could be offered fertility-sparing surgery (FSS) depending on histologic subtypes and prognostic factors. (2) Methods: we conducted a systematic review to assess the safety and fertility outcomes of FSS in the treatment of ovarian cancer. We queried the MEDLINE, PubMed, Cochrane Library, and Cochrane (“Cochrane Reviews”) databases for articles published in English or French between 1985 and 15 January 2021. (3) Results: for patients with BOT, FSS should be offered to young women with a desire to conceive, even if peritoneal implants are discovered at the time of initial surgery. Women with mucinous BOT should undergo initial unilateral salpingo-oophorectomy, whereas cystectomy is an acceptable option for women with serous BOT. Assisted reproductive technology (ART) can be initiated in patients with stage I BOT if infertility persists after surgery. For patients with EOC, FSS should only be considered after staging for women with stage IA grade 1 (and probably 2, or low-grade in the current classification) serous, mucinous or endometrioid tumors. FSS could also be offered to patients with stage IC grade 1 (or low-grade) disease. For women with serous, mucinous or endometrioid high-grade stage IA or low-grade stage IC1 or IC2 EOC, bilateral salpingo-oophorectomy and uterine conservation could be offered to allow pregnancy by egg donation. Finally, FSS has a large role to play in patients with non- epithelial ovarian cancer, and particularly women with malignant ovarian germ cell tumors

Understanding Takeovers and Telestration in Laparoscopic Surgery to Inform Telementoring System Design

International audienceSurgery is primarily taught through mentoring, where an expert mentor supervises a mentee performing surgery, taking over when necessary. Telementoring systems aim to provide mentees with access to remote mentors, but the physical distance between mentors and mentees poses unique challenges to surgical training. We investigate the underlying needs leading to takeovers in onsite mentoring and assess mentors’ ability to fulfill address these needs remotely using existing telestration tools, namely pointers and drawings on shared views. Through interviews and workshops with expert surgeons, we find that (1) mentors take over to convey gestures related to instrument placement, tissue displacement, force, and movement, (2) mentors gather information about location of tissue, equipment, and instruments, as well as gesture constraints, and (3) surgeons judge telestration insufficient for these needs. Based on this gap between onsite mentoring practices and telementoring tools, we discuss novel tools to address these needs and their evaluation

Clinical Value and Molecular Function of Circulating MicroRNAs in Endometrial Cancer Regulation: A Systematic Review

This systematic review of literature highlights the different microRNAs circulating in the serum or plasma of endometrial cancer patients and their association with clinical and prognostic characteristics in endometrial cancer. This study also investigates the molecular functions of these circulating microRNAs. According to this systematic review, a total of 33 individual circulating miRs (-9, -15b, -20b-5p, -21, -27a, -29b, -30a-5p, -92a, -99a, -100, -135b, -141, -142-3p, -143-3p, -146a-5p, -150-5p, -151a-5p, -186, -195-5p, -199b, -200a, -203, -204, -205, -222, -223, -301b, -423-3p, -449, -484, -887-5p, -1228, and -1290) and 6 different panels of miRs (“miR-222/miR-223/miR-186/miR-204”, “miR-142-3p/miR-146a-5p/miR-151a-5p”, “miR-143-3p/miR-195-5p/miR-20b-5p/miR-204-5p/miR-423-3p/miR-484”, “mir-9/miR-1229”, “miR-9/miR-92a”, and “miR-99a/miR-199b”) had a significant expression variation in EC patients compared to healthy patients. Also, seven individual circulating miRs (-9, -21, -27a, -29b, -99a, -142-3p, and -449a) had a significant expression variation according to EC prognostic factors such as the histological type and grade, tumor size, FIGO stage, lymph node involvement, and survival rates. One panel of circulating miRs (“-200b/-200c/-203/-449a”) had a significant expression variation according to EC myometrial invasion. Further studies are needed to better understand their function and circulation

Measuring the quality of learning in a human-robot collaboration: a study of laparoscopic surgery

International audienceRobot-Assisted Laparoscopic Surgery (RALS) is now prevalent in Operating Rooms (ORs). This situation requires future surgeons to learn Classic Laparoscopic Surgery (CLS) and RALS simultaneously. Therefore, along with the investigation of the differences in performance between the two techniques, it is essential to study the impact of training in RALS on the skills mastered in CLS. In this article, we study comanipulated RALS (Co-RALS), one of the two designs for RALS, where the human and the robot share the execution of the task. We use a rarely used in Human-Robot Interaction measuring tool: gaze tracking, and time recording to measure for the acquisition of skills in CLS either when training in Co-RALS or in CLS, and time recording to compare the learning curves between Co-RALS and CLS. These metrics allow us to observe differences in Co-RALS and CLS. Training in Co-RALS develops slightly better but not significantly better hand-eye coordination skills and significantly better time-wise performance compared with training in CLS alone. Co-RALS enhances time-wise performance in laparoscopic surgery on specific type of task that requires precision rather than depth perception skills, compared with CLS. The results obtained enable to further define the Human Robot Interaction quality in Co-RAL

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: &ldquo;immunohistochemistry and microsatellite instability endometrial cancer&rdquo; or &ldquo;immunohistochemistry and mismatch repair endometrial cancer&rdquo; or &ldquo;immunohistochemistry and mismatch repair deficient endometrial cancer&rdquo;. Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities

Reste-t-il des indications de curage ganglionnaire dans les cancers épithéliaux de l’ovaire après l’essai LION ?

International audienceIn March 2019, Harter et al. published the results of the LION study (Lymphadenectomy in patients with advanced ovarian neoplasms) which raises the question of pelvic and para-aortic lymphadenectomy for patients with advanced-stage epithelial ovarian cancer (EOC). These results influenced the new French recommendations published in December 2018 by the French National Cancer Institute (INCa). Thus, it no longer seems consistent to perform a systematic lymphadenectomy for patients for whom there is no argument for nodal involvement, when a macroscopic complete peritoneal cytoreductive surgery has been performed. The question of preoperative lymph node assessment is therefore essential, whereas more than half of the patients in the LION study had metastatic lymph node involvement that was histologically proven. For the assessment of lymph node status by imaging, superior sensitivity for Positron Emission Tomography is demonstrated in comparison with CT-scan or Magnetic Resonance Imaging. Nevertheless, thoraco-abdomino-pelvic CT-scan with contrast injection remains the gold standard for this indication. In the absence of suspected involvement, supra-renal, mesenteric, coelio-hepatic, and cardio-phrenic lymphadenectomy are not recommended. Lymphadenectomies should always be performed in the other situations of EOC management apart from the rare case of stage 1 expansile subtype mucinous carcinoma. The aim of this review is to discuss lymphadenectomy indications for the surgical management of EOC by taking into account new data from the scientific literature