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Purpose. Triple-negative breast cancers (TNBC) are defined as negative for hormonal receptors and human epidermal growth factor receptors 2 and account for 15% of breast cancers. TNBC carry the worst prognosis mainly because of their high proliferation index and the absence of efficient targeted therapies due to their molecular heterogeneity, even though some promising options are emerging. Besides, they do share a very high and distinct tumor-infiltrating lymphocytes (TILs) infiltration. Amongst TILs, CD8+ cytotoxic and CD4+ helper T-cells (TC) proved to be markers of a good outcome. However, pathologists routinely quantify overall TILs density only. Anti-PD-1/PD-L1 immunotherapies recently became available for immunosuppressive TNBC. Unfortunately, neither PD-1/PD-L1 expression nor TILs quantification is able to predict patients’ responses accurately. Thus, we aimed at precisely characterizing TILs sub-populations and evaluating their prognostic significance before their predictive one. Methods. We selected 91 patients at the time of surgery before any adjuvant therapy from January 2013 to December 2018 in Rennes, France. TNBC tumors went through TILs quantification on hematoxylin and eosin slides by a trained pathologist and immune microenvironment characterization using flow cytometry. We then compared the prognostic value of immune microenvironment subpopulations vs total TILs count. Results. TNBCs contained a mean of 22.8±25.9% TILs, including CD4+ TC (14.1%) mainly made of Th2 (11.7%), CD8+ TC (11.1%), and myeloid cells (8.4%) such as antigen presenting cells (APC). TILs groups and percentages were correlated with the abundance of these cellular subpopulations (p≤0.004). TILs percentage was predictive of overall survival (OS), while high APC infiltration was of relapse-free survival (RFS) in univariate analyses (p=0.044 & p≤0.030 respectively). Only Th2 infiltration was predictive of both RFS and OS in univariate (p=0.009 & p=0.008 respectively) and multivariate analyses (p=0.002 & p=0.010 respectively). When considering the different Th populations, only Th2 was a better predictive factor of survival than total leukocytes. Discussion. The development of immune therapies aiming at unlocking the anti-tumor immune response has revealed the desperate need to better characterize the tumor immune infiltrate. TILs quantification by pathologists is the only parameter routinely measured so far but it must be standardized since variability can affect their correlation with pCR. In our study, and contrary to most previous ones, stromal TILs were not significantly associated with RFS and OS. Thus, the characterization of TILs subtypes is critical since they can have either a pro- or an anti-tumorigenic function. Thus, we counteracted the limitations of TILs pathological quantification by finely characterizing the immune infiltrate using flow cytometry. Th2 infiltrate was the most frequent, as previously reported, and counterintuitively, was associated with a favorable prognostic value. This is rarely shown as Th2 infiltration is frequently reported to favor pro-tumorigenic immune tolerance. This proves that a more refined characterization of the intra-tumoral immune landscape is essential to derive interesting therapeutic perspectives, either by recapacitating Th2 response or by targeting their interaction with other immune subsets, like fibroblasts, macrophages, dendritic cells, or eosinophils and IgE. Finally, immunotherapies modulating Th2 response could also be used around the time of surgery that has been proved to induce immunomodulation. Conclusion. The characterization of TILs composition is essential to better understand the potential antitumoral functions of these cells and to substantially improve the associated prognostic and predictive values. Citation Format: Susie Brousse, Florence Godey, Elodie Laffont, Patrick Tas, Boris Campillo-Gimenez, Vincent Lavoué, Matthieu Le Gallo. Evaluation of T-cell infiltrating lymphocytes vs. Th2 in triple negative breast cancers (TNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-23.

International audience; BackgroundAnnotated data are foundational to applications of supervised machine learning. However, there seems to be a lack of common language used in the field of surgical data science.The aim of this study is to review the process of annotation and semantics used in the creation of SPM for minimally invasive surgery videos.MethodsFor this systematic review, we reviewed articles indexed in the MEDLINE database from January 2000 until March 2022. We selected articles using surgical video annotations to describe a surgical process model in the field of minimally invasive surgery. We excluded studies focusing on instrument detection or recognition of anatomical areas only. The risk of bias was evaluated with the Newcastle Ottawa Quality assessment tool. Data from the studies were visually presented in table using the SPIDER tool.ResultsOf the 2806 articles identified, 34 were selected for review. Twenty-two were in the field of digestive surgery, six in ophthalmologic surgery only, one in neurosurgery, three in gynecologic surgery, and two in mixed fields. Thirty-one studies (88.2%) were dedicated to phase, step, or action recognition and mainly relied on a very simple formalization (29, 85.2%). Clinical information in the datasets was lacking for studies using available public datasets. The process of annotation for surgical process model was lacking and poorly described, and description of the surgical procedures was highly variable between studies.ConclusionSurgical video annotation lacks a rigorous and reproducible framework. This leads to difficulties in sharing videos between institutions and hospitals because of the different languages used. There is a need to develop and use common ontology to improve libraries of annotated surgical videos.

In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including protumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines, and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the protumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.

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Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3+ T cells (P = 0.001), comprising both cytotoxic CD8+ (P = 0.01) and CD4+ (P = 0.0062) cells including FoxP3+ regulatory T cells (P = 0.0044). Also, the number of tumor-infiltrating CD20+ B cells (P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [+ (Granzyme B+) cells (HR, 2.63; 95% CI, 1.16–5.95) were independent poor prognostic factors for recurrence, whereas >6,000 CD3+ cells (HR, 0.34; 95% CI, 0.15–0.79) was a good prognostic factor. Thus, low levels of s-CD95L (+ and CD8+, and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker.Implications:Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment.

Table S1. Clinical characteristics of the patients

Figure 1A: Membranous CD95 expression on ovarian cancer cell lines and primary cancer cells by cytometry Figure 1B: Evaluation of epithelial mesenchymal transition expression (EMT) profile using vimentin and E-cadherin expression on ovarian cancer cell line and primary cancer cells by Western Blot (A). Vimentin and E-cadherin expression ratio mean on ovarian cancer cells based on 3 experiments (B). Figure 1C: ALDH1 activity with or without s-CD95L (100 ng/mL) evaluated by cytometry. Figure 1D: Proliferation of OVCAR3 cell lines using cytometry and G1, G2 and S phase markers E: Proliferation of O170 primary cell lines using cytometry and G1, G2 and S phase markers F: Proliferation of various ovarian cancer cell lines or primary cell lines with or without s-CD95L (100 ng/mL) in medium using cytometry and G1, G2 and S phase markers

Purpose To analyze the clinical outcomes and survival curve of arthroscopic lateral patellar facetectomy and lateral release for isolated patellofemoral osteoarthritis (PFOA). Methods All patients undergoing arthroscopic lateral patellar facetectomy and lateral release between January 2008 and January 2018 were evaluated retrospectively. The inclusion criteria were 1) diagnosis of isolated symptomatic lateral PFOA, 2) PFOA with kissing lesions (defined as a lesion on both the patella and trochlea, which were in direct contact, 3) arthroscopic lateral patellar facetectomy and lateral release, and 4) two-year minimum follow-up. Evaluation included preoperative and postoperative subjective International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) scores, and visual analogue pain scale (VAS). The primary end point determining the survival curve was revision of lateral facetectomy. Results A retrospective analysis was conducted of 61 consecutive arthroscopic lateral patellar facetectomy and lateral release procedures, performed in 55 patients for a diagnosis of isolated PFOA. Five patients were lost to follow-up, leaving 56 knees (50 patients) available at a mean follow up of 7.5 years (range: 2-10). The cohort included 37 women and 13 men with a mean age of 59 years (range: 34-87). Nine patients (18%) underwent revision surgery: six total knee replacements (TKR), two high tibial osteotomies, and one revision arthroscopic lateral patellar facetectomy. The mean time from arthroscopic facetectomy to TKR was 51 months (range: 10-114). The survival curve rate was 86% at 7.5 years. Both KOOS and IKDC scores improved significantly. These results are confirmed by an analysis of MCID. The mean VAS decreased from 6.98 ± 1.2 preoperatively to 2.06 ± 1.6 at the last follow-up (ΔCI95% = [−5.6; −4.4]; P = .0001). Conclusion Arthroscopic lateral patellar facetectomy and lateral release for isolated PFOA demonstrates sustained significant improvement in knee clinical outcome scores and pain with a low rate of complications and revision surgery at mid-term follow-up. This operation can be recommended in cases of symptomatic isolated PFOA. Level of Evidence IV, case series

International audience; International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

International audience

Resume Objectif Le cancer du sein associe a la grossesse est une entite complexe tant sur le plan diagnostique que therapeutique, une approche multidisciplinaire est donc essentielle. Un nomogramme predictif de la recidive a 36 mois des CSAG a recemment ete developpe, l’objectif etait de l’evaluer sur une cohorte independante. Methode Il s’agit d’une etude retrospective monocentrique incluant toutes les patientes atteintes d’un CSAG entre janvier 2004 et mars 2018. Une analyse de survie sans recidive a ete realisee par la methode de Kaplan–Meier. La performance du nomogramme a ete analysee sur 3 indicateurs : la discrimination par une courbe ROC (receiver operator characteristic), le calibrage et le benefice clinique net par une courbe d’analyse de decision. Resultat Quarante et une patientes ont ete incluses. La survie sans recidive a 3 ans etait de 83 %. La discrimination du nomogramme etait jugee acceptable avec un index de concordance de l’aire sous la courbe a 0,78. Le modele etait correctement calibre (p = 0,44). L’analyse de la courbe de decision revele un benefice net positif pour un seuil de probabilite de recidive compris entre 5 et 35 %. Conclusion La performance de ce modele de prediction est acceptable mais le benefice clinique net est faible. Predire le risque de recidive reste un challenge et des outils plus precis sont necessaires.

Resume Objectif Nous ne disposons pas, en France, d’un parcours identifie pour la formation en chirurgie cancerologie gynecologique. Les quatre societes savantes francaises competentes : la SFOG, Le CNGOF, la SFCO et la SCGP soutenus par le CNU de gynecologie-Obstetrique et d’UNICANCER se sont entendues pour materialiser ce parcours et l’attester par une certification decernee par un jury national. Materiel et methodes Le comite national de certification en cancerologie gynecologique, constitue de dix membres, representant les six organismes concernes, s’est fixe cinq objectifs : la definition des criteres d’eligibilite des centres pour la formation ; la determination d’un cahier des charges a remplir par le candidat ; la determination d’un cursus fleche pour la formation en chirurgie cancerologique gynecologique ; la determination des acquis necessaires pour la certification d’un candidat deja en exercice et l’organisation pratique de la certification. Resultats Les criteres d’agrement des centres pour la formation, incluent 150 prises en charge de cancers gynecologiques, dont 100 chirurgies d’exerese, comprenant vingt cancers de l’ovaire de stades avances. Pour une certification a l’issue du cursus etabli par le comite ou par validation des acquis pour un praticien en exercice, un candidat doit valider un logbook et remplir un cahier des charges comportant quatre volets : formation theorique et pratique ; recherche et publications ; enseignements et souscription a une demarche de formation continue. Les elements du logbook et du cahier des charges accomplis seront evalues par un score. Une premiere session de certification est prevue pour la fin 2021.

International audience; Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/ expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic /para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.

International audience; Non-tubal ectopic pregnancies can be located in the uterine portion of the tube (interstitial or cornual), in the cervix (cervical), in a cesarian scar, in the ovary, or intra-abdominally. Even though they are rare, they are associated with a high mortality. Invasive surgeries such as cornuectomy and hysterectomy were common to treat them in case of hemorrhage. Thanks to recent advances in imaging techniques, diagnosis of non-tubal ectopic pregnancy is made earlier and conservative management has been developed in order to respect fertility of patients. Beyond these treatments, systemic or local injection of Methotrexate shows very good success.In the article, we aimed to describe the technics of vaginal injection of in situ methotrexate with ultrasound guidance.

The presence of lymphovascular space invasion (LVSI) is not yet included in international recommendations neither as a prognostic factor nor as a parameter for the decision to use adjuvant chemotherapy in FIGO stage I/IIa ovarian cancer (OC).This study set out to evaluate the impact of LVSI on Overall Survival (OS) and Recurrence-Free Survival (RFS) in patients managed for epithelial OC.Retrospective multicenter study by the research group FRANCOGYN between January 2001 and December 2018. All patients managed for epithelial OC surgery and for whom histological slides for the review of LVSI were available, were included. The characteristics of patients with LVSI (LVSI group) were compared to those without LVSI (No-LVSI group). A Cox analysis for OS and RFS analysis was performed in all the populations.French multicenter tertiary care centers RESULTS: Over the study period, 852 patients were included in the 13 institutions. Among them, 289 patients had LVSI (33.9%). There was a significant difference in the distribution of LVSI between early and advanced stages (p 0.001). LVSI was an independent predictive factor for poorer Overall and Recurrence-Free Survival. LVSI affected OS (p 0.001) and RFS (p 0.001), LVSI affected OS and RFS for early stages (p = 0.001; p = 0.001, respectively) and also for advanced stages (p = 0.01; p = 0.009, respectively).The presence of LVSI in epithelial ovarian epithelial tumors has an impact on OS and RFS and should be included in the routine pathology examination to adapt therapeutic management, especially for women in the early stages of the disease.

International audience; Schwannomas are benign nerve tumors arising mainly in the intracranial, cervical, or lumbar regions. We describe the case of a presacral schwannoma in a 42-year-old woman. This atypical localization is most often discovered by symptoms related to compression of nervous structures. Our patient presented only with deep dyspareunia. The schwannoma was diagnosed on MRI which revealed a presacral hyperintense mass with an antero-posterior diameter of 47 mm opposite the S3 sacral orifice. After 6 years of follow-up, the mass was resected because of worsening dyspareunia and sudden lesion growth. The resection was performed through an open abdominal anterior approach and resulted in alleviation of the symptoms without postoperative complications. To our knowledge, this is the first case of pelvic schwannoma expressing a gynecological symptom such as dyspareunia.

Resume Objectif L’objet de cette revue de la litterature est de faire le point sur les evolutions de la transplantation uterine (TU) dans le monde et de developper les nouveaux questionnements poses par cette technique en 2020. Methodes Selon le modele PRISMA, via PubMed nous avons recherche les publications contenant les mots-cles : uterus transplantation et UT and cryopreservation entre 2000 et 2020. Resultats Au moins 76 TU ont ete realisees dans le monde ayant permis la naissance de 19 enfants en bonne sante. L’indication princeps reste l’agenesie uterine (syndrome MRKH > 85 % cas) puis l’antecedent d’hysterectomie (hemorragie de la delivrance ou cancer du col) et l’uterus non fonctionnel (syndrome d’Asherman, adenomyose diffuse). Les deux types de donneuses (vivantes et decedees) sont developpes representant respectivement 75 % et 25 % des TU ; le taux de succes en termes de retour des regles est superieur dans le groupe donneuse vivante et est de 79 % vs 68 % dans le groupe donneuse decedee. Le choix du type de donneuse doit tenir compte des contraintes des deux procedures. Les complications chirurgicales (grade III) pour la donneuse sont estimees a 14 % representees essentiellement par des plaies de l’uretere. Des simplifications techniques concernant le retour veineux du greffon mais aussi la realisation d’une chirurgie robot-assistee permettraient de diminuer le temps operatoire pour la donneuse et de faciliter le geste de prelevement. Conclusion La TU est une alternative complementaire a la gestation pour autrui (GPA) et a l’adoption permettant aux patientes d’etre mere porteuse, legale et biologique de l’enfant. Les potentielles complications chez la donneuse doivent etre prises en compte dans ce choix. Un elargissement des indications vers les patientes souffrant d’infertilite uterine non absolue est en cours de reflexion.

Objective To assess the diagnostic and prognostic characteristics of borderline ovarian tumours (BOTs) detected during pregnancy, and to establish an inventory of French practices. Materials and methods A retrospective multi-centre case study of 14 patients treated for BOTs, diagnosed during pregnancy between 2005 and 2017, in five French pelvic cancerology expert centres, including data on clinical characteristics, histological tumour characteristics, surgical procedure, adjuvant treatments, follow-up and fertility. Results The mean age of patients was 29.3 [standard deviation (SD) 6.2] years. Most BOTs were diagnosed on ultrasonography in the first trimester (85.7 %), and most of these cases (78.5 %) also underwent magnetic resonance imaging to confirm the diagnosis (true positives 54.5 %). Most patients underwent surgery during pregnancy (57 %), with complete staging surgery in two cases (14.3 %). Laparoscopy was performed more frequently than other procedures (50 %), and unilateral adnexectomy was more common than cystectomy (57.5 %). Tumour size influenced the surgical approach significantly (mean size 7.5 cm for laparoscopy, 11.9 cm for laparoconversion, 14 cm for primary laparotomy; P = 0.08), but the type of resection did not. Most patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IA (92.8 %) tumours, but many were upstaged after complete restaging surgery (57.1 %). Most BOTs were serous (50 %), two cases had a micropapillary component (28.5 %), and one case had a micro-invasive implant. BOTs were bilateral in two cases (14.2 %). Mean follow-up was 31.4 (SD 14.8) months. Recurrent lesions occurred in two patients (14.2 %) and no deaths have been recorded to date among the study population. Conclusion BOTs remain rare, but this study – despite its small sample size – supports the hypothesis that BOTs during pregnancy have potentially aggressive characteristics.

AimsWe aimed to address the question on whether there is a place for shoulder stabilization surgery in patients who had voluntary posterior instability starting in childhood and adolescence, and later becoming involuntary and uncontrollable.MethodsConsecutive patients who had an operation for recurrent posterior instability before the age of 18 years were studied retrospectively. All patients had failed conservative treatment for at least six months prior to surgery; and no patients had psychiatric disorders. Two groups were identified and compared: voluntary posterior instability starting in childhood which became uncontrollable and involuntary (group VBI); and involuntary posterior instability (group I). Patients were reviewed and assessed at least two years after surgery by two examiners.ResultsIn all 38 patients (40 shoulders) were included: group I (20 shoulders), with involuntary posterior instability (onset at 14 years of age (SD 2.3), and group VBI (20 shoulders), with initially voluntary posterior instability (onset at 9 years of age (SD 2.6) later becoming involuntary (16 years of age (SD 3.5). Mean age at surgery was 20 years (SD 4.6 years; 12 to 35). A posterior bone block was performed in 18 patients and a posterior capsular shift in 22. The mean follow-up was 7.7 years (2 to 18). Recurrence of posterior instability was seen in nine patients, 30% in group VBI (6/20 shoulders) and 15% in group I (3/20 shoulders) (p > 0.050). At final follow-up, the shoulder's of two patients in each group had been revised. No differences between either group were found for functional outcomes, return to sport, subjective, and radiological results.ConclusionAlthough achieving stability in patients with so-called voluntary instability, which evolves into an involuntary condition, is difficult, shoulder stabilization may be undertaken with similar outcomes to those patients treated surgically for involuntary instability. Cite this article: Bone Joint J 2020;102-B(12):1760–1766.

International audience; BACKGROUND: This study compares morbidity and mortality associated with retroperitoneal and transperitoneal para-aortic lymphadenectomy (PAAL) for pretherapeutic nodal staging of locally advanced cervical cancers (FIGO IB3-IVA). METHODS: Pre-, per- and postoperative data of patients treated for locally advanced stage cervical cancer between 1999 and 2018 in 12 French referral centers (FRANCOGYN Study Group) were retrospectively collected. RESULTS: The study was conducted using a sample of 448 patients, of whom 223 (49,8%) underwent retroperitoneal (group 1) and 225 (50,2%) had transperitoneal PAAL (group 2). No differences were noted concerning clinical and histological characteristics between the two groups. Among these 448 patients, 23 (5,1%) had an intraoperative complication (9 (2,0%) in group 1 and 14 (3,1%) in group 2, p = 0.28) and 47 (10,5%) had a postoperative complication (22 (4,9%) in group 1 and 25 (5,6%) in group 2, p = 0.44), only one of which required revision surgery but the patient died. The length of hospital stay was significantly shorter in group 1 than in group 2 (3.97 versus 4.88 days, p

International audience; INTRODUCTION: Endometriosis is a chronic inflammatory disease with a negative impact on fertility. The Enzian classification provides a precise description of deep pelvic endometriotic lesions, especially in the retroperitoneal area, from preoperative pelvic MRI scans. However, it is not known if it is correlated with postoperative fertility. STUDY OBJECTIVE: To determine if there is an association between the preoperative Enzian score and postoperative fertility after deep pelvic endometriosis surgery. DESIGN: We conducted a descriptive, retrospective study using information from the ENDOREN database. SETTING: This was a retrospective study at the Department of Obstetrics and Gynecology at Rennes University Hospital (France) from January 2013 to May 2019 PATIENTS AND INTERVENTIONS: We used information from the ENDOREN database that included all women who underwent surgery for deep endometriosis and wish to conceive. This surgery was intended in a view to achieve a complete removal of endometriosis. MEASUREMENTS: The Enzian score was calculated from preoperative MRI scans, and total, spontaneous, and after In Vitro fertilization (IVF) live births and pregnancies outcomes were collected from the patients’computerized medical records. Univariate and multivariate analysis was performed. RESULTS: Sixty-eight patients were included. The live-birth rate was 35% (24/68). According to the Enzian classification, 25 patients (35%) were classified in compartment A, 64 patients (94%) in compartment B, and 27 (40%) in compartment C. In multivariate analysis, positive predictor of live birth was single Enzian B score (OR=4.7[1.21; 18.81], p = 0.03), negative predictors were uterine adenomyosis and a history of endometriosis surgery. In multivariate analysis, positive predictor of spontaneous live birth was EFI score ≥7 (OR =22.434; CI [1.138; 442.190]). In multivariate analysis, positive predictor was Enzian A score (OR=15.9[2.2; 114.7], p = 0.006), and negative predictors was uterine adenomyosis and Enzian B score (OR=0.01[0; 0.495], p = 0.02) for live birth after IVF. CONCLUSION: The present retrospective study cannot strongly conclude about fertility and correlation with Enzian score because the groups are too small. However, it seems that when solely the compartment B is involved by endometriosis, complete full removal of endometriosis leads to better post-operative live births results. Other studies must be done to determine if Enzian classification based on preoperative pelvic MRI could be clinical value in the decision-making strategy for managing infertile patients with deep pelvic endometriosis.

International audience

Resumen Las lesiones intraepiteliales del cuello uterino tienen relacion con el virus del papiloma humano (VPH) y actualmente, por ejemplo en Francia, se detectan mediante frotis cervicouterino (en espera de la puesta en marcha de la deteccion precoz virologica organizada). Se distinguen las lesiones escamosas de bajo grado, que no se consideran lesiones premalignas pero en las que predominan los VPH de alto riesgo, lo cual justifica un seguimiento, de las lesiones de alto riesgo escamosas, que tienen riesgo de degeneracion maligna y requieren un tratamiento y vigilancia. Las recomendaciones francesas precisan las indicaciones terapeuticas, que privilegian, en caso de lesion de bajo grado, una vigilancia y, en caso de lesion de alto grado, un tratamiento (o bien destruccion en las lesiones menos graves, poco amplias y claramente identificadas, o bien, con mayor frecuencia, exeresis con control colposcopico [para preservar al maximo el cuello], que permite un analisis exhaustivo de estas lesiones). Actualmente, el pilar de la vigilancia de estas lesiones es la prueba del VPH, que por regla general se realiza inicialmente 6 meses despues del tratamiento y se propone despues a largo plazo. Aparte, estan las lesiones de adenocarcinoma in situ, mas raras, de deteccion y diagnostico mas dificiles, cuyo tratamiento es la histerectomia, con la opcion, en las pacientes con un proyecto de embarazo, de tratamiento de exeresis con la condicion de retirar todas las lesiones y de aceptar el principio de una vigilancia prolongada.

International audience; Introduction The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery.Materials and methods Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival.Results The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16–3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01–2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC.Conclusion In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

STUDY QUESTION Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis and ovary development in humans? SUMMARY ANSWER The characterization of a dynamically regulated protein-coding and non-coding transcriptional landscape in developing human gonads of both sexes highlights a large number of potential key regulators that show an early sexually dimorphic expression pattern. WHAT IS KNOWN ALREADY Gonadal sex differentiation is orchestrated by a sexually dimorphic gene expression program in XX and XY developing fetal gonads. A comprehensive characterization of its non-coding counterpart offers promising perspectives for deciphering the molecular events underpinning gonad development and for a complete understanding of the etiology of disorders of sex development in humans. STUDY DESIGN, SIZE, DURATION To further investigate the protein-coding and non-coding transcriptional landscape during gonad differentiation, we used RNA-sequencing (RNA-seq) and characterized the RNA content of human fetal testis (N = 24) and ovaries (N = 24) from 6 to 17 postconceptional week (PCW), a key period in sex determination and gonad development. PARTICIPANTS/MATERIALS, SETTING, METHODS First trimester fetuses (6–12 PCW) and second trimester fetuses (13–14 and 17 PCW) were obtained from legally induced normally progressing terminations of pregnancy. Total RNA was extracted from whole human fetal gonads and sequenced as paired-end 2 × 50 base reads. Resulting sequences were mapped to the human genome, allowing for the assembly and quantification of corresponding transcripts. MAIN RESULTS AND THE ROLE OF CHANCE This RNA-seq analysis of human fetal testes and ovaries at seven key developmental stages led to the reconstruction of 22 080 transcripts differentially expressed during testicular and/or ovarian development. In addition to 8935 transcripts displaying sex-independent differential expression during gonad development, the comparison of testes and ovaries enabled the discrimination of 13 145 transcripts that show a sexually dimorphic expression profile. The latter include 1479 transcripts differentially expressed as early as 6 PCW, including 39 transcription factors, 40 long non-coding RNAs and 20 novel genes. Despite the use of stringent filtration criteria (expression cut-off of at least 1 fragment per kilobase of exon model per million reads mapped, fold change of at least 2 and false discovery rate adjusted P values of less than LARGE-SCALE DATA Raw data files (fastq) and a searchable table (.xlss) containing information on genomic features and expression data for all refined transcripts have been submitted to the NCBI GEO under accession number GSE116278. LIMITATIONS, REASONS FOR CAUTION The intrinsic nature of this bulk analysis, i.e. the sequencing of transcripts from whole gonads, does not allow direct identification of the cellular origin(s) of the transcripts characterized. Potential cellular dilution effects (e.g. as a result of distinct proliferation rates in XX and XY gonads) may account for a few of the expression profiles identified as being sexually dimorphic. Finally, transcriptome alterations that would result from exposure to pre-abortive drugs cannot be completely excluded. Although we demonstrated the high quality of the sorted cell populations used for experimental validations using quantitative RT-PCR, it cannot be totally excluded that some germline expression may correspond to cell contamination by, for example, macrophages. WIDER IMPLICATIONS OF THE FINDINGS For the first time, this study has led to the identification of 1000 protein-coding and non-coding candidate genes showing an early, sexually dimorphic, expression pattern that have not previously been associated with sex differentiation. Collectively, these results increase our understanding of gonad development in humans, and contribute significantly to the identification of new candidate genes involved in fetal gonad differentiation. The results also provide a unique resource that may improve our understanding of the fetal origin of testicular and ovarian dysgenesis syndromes, including cryptorchidism and testicular cancers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the French National Institute of Health and Medical Research (Inserm), the University of Rennes 1, the French School of Public Health (EHESP), the Swiss National Science Foundation [SNF n° CRS115_171007 to B.J.], the French National Research Agency [ANR n° 16-CE14-0017-02 and n° 18-CE14-0038-02 to F.C.], the Medical Research Council [MR/L010011/1 to P.A.F.] and the European Community’s Seventh Framework Programme (FP7/2007-2013) [under grant agreement no 212885 to P.A.F.] and from the European Union’s Horizon 2020 Research and Innovation Programme [under grant agreement no 825100 to P.A.F. and S.M.G.]. There are no competing interests related to this study.

INTRODUCTION: Recommendations for the management of patients with gynecological cancer during the COVID-19 pandemic period. MATERIAL AND METHOD: Recommendations based on the consensus conference model. RESULTS: In the case of a COVID-19 positive patient, surgical management should be postponed for at least 15 days. For cervical cancer, the place of surgery must be re-evaluated in relation to radiotherapy and Radio-Chemotherapy-Concomitant and the value of lymph node staging surgeries must be reviewed on a case-by-case basis. For advanced ovarian cancers, neo-adjuvant chemotherapy should be favored even if primary cytoreduction surgery could be envisaged. It is lawful not to offer hyperthermic intraperitoneal chemotherapy during a COVID-19 pandemic. In the case of patients who must undergo interval surgery, it is possible to continue the chemotherapy and to offer surgery after 6 cycles of chemotherapy. For early stage endometrial cancer, in case of low and intermediate preoperative ESMO risk, hysterectomy with bilateral annexectomy associated with a sentinel lymph node procedure should be favored. It is possible to consider postponing surgery for 1 to 2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For high ESMO risk, it ispossible to favor the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) in order to omit pelvic and lumbar-aortic lymphadenectomies. CONCLUSION: During COVID-19 pandemic, patients suffering from cancer should not lose life chance, while limiting the risks associated with the virus.

Objective The purpose of this study was to compare two groups of patients presenting advanced ovarian carcinoma benefiting from neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery: after 3–4 cycles (group 1) or ≥ 5 cycles (group 2), regarding overall survival (OS) and progression-free survival (PFS), complications related to surgery as well as the extent of cytoreduction were assessed. Study design We conducted a retrospective, multicenter cohort study in nine referral centers of France, reviewing the charts of all patients who underwent NAC between January 2000 and June 2017. We performed an OS analysis using multivariate Cox regression models adjusted for potential confounders. We also analyzed PFS and surgery-related morbidity. Results Of 501 patients included, 236 (47.1 %) benefited from ≤ 4 NAC cycles and 265 (52.9 %) from ≥ 5 NAC cycles. Characteristics data were similar in both groups. The rate of achievement of complete surgery was similar in both groups (p = 0.28). Surgical morbidity and postoperative complications showed no significant differences between both groups. The median OS was 54.2 months, 64 months for group 1 and 49.2 months for group 2. The 5-year survival rate was 45.6 % and 27.6 %. This difference was not statistically significant [HR 1.81 (0.89–3.71), p = 0.09]. Five-year PFS was 19.7 % and 11.7 % respectively (p = 0.31). Conclusion In a large series of advanced ovarian cancer, patients receiving late IDS (≥ 5 NAC cycles) seem to show a poorer prognosis than patients operated on earlier. The survival appears to be mainly determined by optimal resection and response to chemotherapy.

Because of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e.,2 cm), with shallow stromal invasion (10 mm) and without the presence of lymph-vascular space invasion or lymph node or regional involvement. Under these conditions, conservative treatment by trachelectomy, which has recurrence-free and overall survival rates equivalent to that of hysterectomy, may be considered. After a complete pre-therapeutic assessment, including pelvic lymphadenectomy, to eliminate all contraindications to conservative treatment, a simple or enlarged trachelectomy can be chosen. According to some authors, the route of entry (vaginal, simple or robot-assisted laparoscopy, laparotomy) has no significant effect on survival or fertility, although the literature on the subject is limited. Trachelectomy offers good results in terms of fertility, with an estimated pregnancy rate of between 23% and 55% and a live birth rate of 70%. The significant reduction of the cervix associated with the procedure increases the risk of prematurity. However, this can be prevented by the use of a permanent cerclage. Close follow-up of these patients is essential for a minimum period of 5 years in order to detect any recurrence or postoperative complications.

Context Acetaminophen (APAP, paracetamol) is widely used by pregnant women. Although long considered safe, growing evidence indicates that APAP is an endocrine disruptor since in utero exposure may be associated with a higher risk of male genital tract abnormalities. In rodents, fetal exposure has long-term effects on the reproductive function of female offspring. Human studies have also suggested harmful APAP exposure effects. Objective Given that disruption of fetal ovarian development may impact women’s reproductive health, we investigated the effects of APAP on fetal human ovaries in culture. Design and Setting Human ovarian fragments from 284 fetuses aged 7 to 12 developmental weeks (DW) were cultivated ex vivo for 7 days in the presence of human-relevant concentrations of APAP (10−8 to 10−3 M) or vehicle control. Main Outcome Measures Outcomes included examination of postculture tissue morphology, cell viability, apoptosis, and quantification of hormones, APAP, and APAP metabolites in conditioned culture media. Results APAP reduced the total cell number specifically in 10- to 12-DW ovaries, induced cell death, and decreased KI67-positive cell density independently of fetal age. APAP targeted subpopulations of germ cells and disrupted human fetal ovarian steroidogenesis, without affecting prostaglandin or inhibin B production. Human fetal ovaries were able to metabolize APAP. Conclusions Our data indicate that APAP can impact first trimester human fetal ovarian development, especially during a 10- to 12-DW window of heightened sensitivity. Overall, APAP behaves as an endocrine disruptor in the fetal human ovary.

International audience; Objective - In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies, the SFOG, the CNGOF, the SFCO and the SCGP, supported by the CNU of Obstetrics &Gynaecology- and UNICANCER, agreed to materialize this course and attest it by a certification awarded by a national jury. Material and methods - The national committee of certification in gynaecological oncology made up of 10 members, representing the 6 concerned organizations, set itself 5 objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification. Results - Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including 20 advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including 4 parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021. Conclusion - The optimisation of the surgical management of patients treated for gynaecological cancer is achieved through the identification of a training course and the certification, by a national jury, of the skills of surgeons who have completed it.

International audience

International audience; Introduction: The objective of this work is to report the first 6 months of a robotic program in a surgical gynecological team, trained in advanced laparoscopy, in terms of operating times, complication rate, analgesic consumption and average duration of hospitalization.Methods: This is a prospective observational study, intended to treat.Results: During the study period, 98 women underwent laparoscopic robot assisted surgery. The average BMI was 27.2 kg/m2 (± 7). Malignant diseases accounted for 41% of operative indications. Comparing the first 30 procedures to the last 30 procedures, there is a significant decrease in docking times: 14.7 min (± 7.0) vs 8.9 min (± 5.0), P = 0.009. There is also a trend towards a decrease in operative times for hysterectomy: 151.9 min (± 56.2) vs 113 min (± 51.4), P = 0.08. The rates of complications were not significantly different at the beginning and end of inclusion during the study (10.0% vs 16.7%).Conclusion: The implementation of a robotic surgery program in a gynecological surgery department does not lead to an increase in complications for the patients, including for the first procedures. The learning curve mainly allows a reduction in the robot's installation time.; Introduction: L’objectif de ce travail est de rapporter les 6 premiers mois d’un programme robotique dans une équipe chirurgicale gynécologique, rodée à la cœlioscopie avancée, en termes de durées opératoires, taux de complications, consommation d’antalgiques et durée moyenne d’hospitalisation.Méthodes: Il s’agit d’une étude observationnelle prospective, en intention de traiter.Résultats: Sur la période de l’étude, 98 femmes ont été opérées par cœlioscopie robot assistée. L’IMC moyen était de 27,2 kg/m2 (± 7). Les pathologies malignes représentaient 41 % des indications opératoires. En comparant les 30 premières procédures aux 30 dernières procédures ; on observe une diminution significative des temps de docking avec l’expérience : 14,7 min (± 7.0) vs 8,9 min (± 5.0), p = 0,009. On observe également une tendance à une diminution des temps opératoires pour l’hystérectomie simple : 151,9 min (± 56,2) vs 113 min (± 51,4), p = 0,08. Les taux de complications ne sont pas significativement différents en début et en fin d’expérience au cours de l’étude (10,0 % vs 16,7 %).Conclusion: La mise en place d’un programme de chirurgie robotique dans un service de chirurgie gynécologique n’entraine pas une augmentation des complications pour les patientes, y compris pour les premières procédures. La courbe d’apprentissage permet surtout une diminution des temps d’installation du robot.

International audience; BACKGROUND: The aim of this study was to evaluate the impact of lymphovascular space invasion (LVSI) on overall survival (OS) and recurrence-free survival (RFS) in patients managed for stage I-IIa clear cell carcinoma, mucinous, low-grade serous and low-grade endometrioid ovarian cancer MATERIAL AND METHODS: Retrospective multicentre study of the research group FRANCOGYN between January 2001 and December 2018. All patients managed for stage I-IIa clear cell carcinoma, mucinous /low grade serous and endometrioid ovarian cancer and for whom the presence of histological slides for the review of LVSI was available, were included. Patient’s characteristics with LVSI (LVSI group) were compared to those without LVSI (No LVSI group). A cox analysis for OS and RFS analysis were performed in all population. RESULTS: Over the study period, 133 patients were included in the thirteen institutions. Among them, 12 patients had LVSI (9%). LVSI was an independent predictive factor for poorer Overall and recurrence free survivals. LVSI affected OS (p