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Background: Acrylamide is classified as a probable human carcinogen by the IARC but epidemiological evidence on the carcinogenicity of acrylamide from dietary sources is limited. This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort. Methods: This prospective cohort study included 80,597 French women (mean [SD] age at baseline: 40.8 [14] years) during a mean (SD) follow-up of 8.8 (2.3) years. Acrylamide intake was evaluated using repeated 24h dietary records (n= 5.5 [SD 3.0]), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal and post-menopausal) were assessed by Cox hazard models adjusted for known risk factors. Results: The mean (SD) dietary acrylamide intake was 30.1 (21.9) µg/d (main contributors: coffee, potato fries and chips, pastries and cakes, and bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between acrylamide intake and breast cancer risk overall (HRQ4 vs Q1= 1.21 [95% CI: 1.00-1.47]) and a positive association was observed with premenopausal cancer (HRQ4 vs Q1= 1.40 [95% CI: 1.04-1.88]). Restricted cubic spline analyses suggested evidence for non-linearity of these associations, with higher HR for intermediate (Q2) and high (Q4) exposures. Receptor-specific analyses revealed a positive association with estrogen receptor-positive breast cancer, which represented 86% of total cancer cases. Acrylamide intake was not associated with post-menopausal breast cancer. Conclusions: Results from this large prospective cohort study suggest the potential deleterious role of dietary acrylamide in breast cancer etiology, especially in premenopausal women, and provide new insights that should encourage further mitigation strategies to reduce the content of acrylamide in food. Citation Format: Alice Bellicha, Gaëlle Wendeu-Foyet, Xavier Coumoul, Meriem Koual, Fabrice Pierre, Françoise Guéraud, Laurent Zelek, Charlotte Debras, Bernard Srour, Laury Sellem, Emmanuelle Kesse-Guyot, Chantal Julia, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier. Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort [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 P2-06-03.

Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited.This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status.This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors).The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer.Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

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.

The role of the environment in breast cancer (BC) progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor its aggressivity. We also evaluated the impact of the micro-environment, largely represented by adipocytes, in mediating this.BC cells lines MCF-7 were cultured using a transwell co-culture model with preadipocytes hMADS cells or were cultured alone. Cells were treated by cigarette smoke extract (CSE) and the four conditions: control, CSE, co-culture and co-exposure (co-culture and CSE) were compared. We analyzed morphological changes, cell migration, resistance to anoikis, stemness, epithelial to mesenchymal transition (EMT) and presence of hormonal receptors in each condition. A complete transcriptomic analysis was carried out to highlight certain pathways.Several hallmarks of metastasis were specific to the coexposure condition (cell migration, resistance to anoikis, stemness) whereas others (morphological changes, EMT, loss of hormonal receptors) could be seen in the coculture condition and were aggravated by CSE (coexposure). Moreover, MCF-7 cells presented a decrease in hormonal receptors, suggesting an endocrine treatment resistance. These results were confirmed by the transcriptomic analysis. Our in vitro results suggest that a common mixture of pollutants could promote BC metastasis in a co-culture model.

International audience; Medical reports are key elements to guarantee the quality, and continuity of care but their quality remains an issue. Standardization and structuration of reports can increase their quality, but are usually based on expert opinions. Here, we hypothesize that a structured model of medical reports could be learnt using machine learning on retrospective medical reports extracted from clinical data warehouses (CDW). To investigate our hypothesis, we extracted breast cancer operative reports from our CDW. Each document was preprocessed and split into sentences. Clustering was performed using TFIDF, Paraphrase or Universal Sentence Encoder along with K-Means, DBSCAN, or Hierarchical clustering. The best couple was TFIDF/K-Means, providing a sentence coverage of 89 % on our dataset; and allowing to identify 7 main categories of items to include in breast cancer operative reports. These results are encouraging for a document preset creation task and should then be validated and implemented in real life.

International audience; Background: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD.Methods: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples). The RNAseq score was applied in independent gynaecological datasets (CARPEM/CPTAC/SCAN/TCGA, N = 4038 samples). Validations used ROC curves, linear regressions and Pearson correlations. Overall survival (OS) analyses used Kaplan-Meier curves and Cox models.Results: In total, 656 genes were commonly up/downregulated with gHRD score in UCEC/BRCA/OV. Upregulated genes were enriched for nuclear/chromatin/DNA-repair processes, while downregulated genes for cytoskeleton (gene ontologies). The RNAseq score correlated with gHRD score in independent gynaecological cancers (R² = 0.4-0.7, Pearson correlation = 0.64-0.86, all P < 10-11), and was predictive of gHRD score >42 (RNAseq HRD profile; AUC = 0.95/0.92/0.78 in UCEC/BRCA/OV). RNAseq HRD profile was associated (i) with better OS in platinum-treated advanced TP53-mutated-UCEC (P < 0.001) and OV (P = 0.013), and (ii) with poorer OS (P < 0.001) and higher benefit of adjuvant chemotherapy in Stage I-III BRCA (interaction test, P < 0.001).Conclusions: UCEC/BRCA/OV with HRD-associated genomic scars share a common transcriptional profile. RNAseq signatures might be relevant for identifying HRD-gynaecological cancers, for prognostication and for therapeutic decision.

Resume Les patientes porteuses d’une mutation du gene BReast Cancer 1 ou 2 (BRCA) ont une predisposition hereditaire aux cancers du sein et de l’ovaire. Ces mutations genetiques deleteres sont celles les plus couramment impliquees dans les cancers hereditaires du sein et de l’ovaire. La consultation d’oncogenetique joue un role cle dans l’identification des patientes a risque et la recherche et l’identification de la mutation chez la patiente et ses apparentes. La mise en evidence d’une mutation BRCA doit conduire a une surveillance rapprochee et peut justifier d’une chirurgie prophylactique mammaire et/ou annexielle dont les indications et les modalites sont detaillees par l’Institut national du cancer (INCa). Les inhibiteurs de poly-(ADN-riboses) polymerases (PARP), dont le plus connu est l’olaparib ont une efficacite majeure dans la prise en charge des cancers epitheliaux de l’ovaire chez les patientes porteuses d’une mutation BRCA et les nombreuses etudes en cours elargiront probablement les indications dans un futur proche.

Introduction/Background* Because of inter-tumor heterogeneity of endometrial carcinoma (EC), prognostication remains challenging. We aimed to develop a RNAseq signature to stratify EC patient prognosis beyond molecular subtyping. Methodology A prognostic signature was identified using a LASSO-penalized Cox regression model on TCGA (N=543 patients). A polyA-RNAseq-based method was developed for validation of the signature in a cohort of stage I-IV EC patients treated in two Paris Hospitals between 2010 and 2017. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated using uni/multivariable Cox models (hazard ratio (HR) with [95% confidence interval]) and Kaplan-Meier analysis. Result(s)* Among 209 patients included in the validation cohort (median follow-up 55 months IQR [41-69]), 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC=80%). Using a composite classifier accounting for the RNAseq signature and the TP53-mutated group, three groups were identified: good prognosis tumors based on RNAseq signature and without TP53 mutation, characterized by excellent outcome (N=103 patients, 5-years DSS rates of 99%) (reference), poor prognosis tumors based on RNAseq signature and without TP53 mutation (N=49 patients, 5-years DSS rates of 81%; HR: 5.86 [1.16; 29.7]), and TP53-mutated tumors whatever the RNAseq signature (N=52 patients, 5-years DSS rates of 52%; HR: 11.14 [2.40; 51.7]) (HR adjusted on FIGO stage). In 81 (38%) patients with adverse features (2020 ESGO/ESTRO/ESP guidelines: non-endometrioid histology or stage III-IVA or TP53-mutated tumors), TP53-mutated molecular group was not significantly associated with poor prognosis (p=0.18). A The composite classifier identified three classes within this subgroup: RNAseq-good prognosis (N=24), non-TP53/RNAseq-poor prognosis (N=16), and TP53-mutated tumors (N=41), with 5-years DSS rates of 100%, 59%, and 71%, respectively (p=0.015). Transcriptome analyses suggested the underlying involvement of immune deprivation and wound healing processes in tumors with poor prognosis. Conclusion* We demonstrate that RNAseq characterization can refine prognostication in EC beyond molecular subgroups and main prognostic features, and warrants validation for potential RNAseq-based adjuvant therapeutic strategies in EC.

Introduction/Background* Recent findings have suggested that lymphadenectomy during primary cytoreductive surgery (CRS) in patients with ovarian cancer was not associated with an improve in survival, at the expense of a high morbidity. The aim of our study was to evaluate the impact of lymphadenectomy in patients with high-grade serous ovarian cancer benefitting from neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Methodology A retrospective, unicentric study including all patients undergoing NACT and IDS was carried out from 2005-2018. Patients with and without lymphadenectomy were compared in terms of recurrence free survival (RFS), overall survival (OS), and complication rates. Survival was assessed using a Cox regression model and Kaplan Meyer curves. Result(s)* We included 203 patients. Of these, 133 had a lymphadenectomy (65.5%) and 77 had involved nodes (57.9%). Patients who did not benefit from a lymphadenectomy were older with a more extensive disease and lesser rate of complete CRS. No differences were noted between the lymphadenectomy and no lymphadenectomy group concerning 2-year RFS (47.4% and 48.6%, p=0.87, respectively) and 5-year OS (63.2% versus 58.6%, p=0.41, respectively). Post-operative complications tended to be more frequent in the group with a lymphadenectomy (18.57 versus 31.58, p=0.09). In the group of patients with lymphadenectomy, survival was significantly altered in patients with involved nodes (positive lymph nodes: 2-year RFS 42.5% and 5-year OS 49.4%, negative nodes: 2-year RFS 60.7% and 5-year OS 82.2%, p= 0.03 and p Conclusion* Lymphadenectomy during IDS does not improve survival and increases post-operative complications.

Introduction/Background* The benefit of a systematic lymphadenectomy is still debated in patients undergoing neo-adjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. Methodology A retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005-2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. Result(s)* 158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at ‘high risk’ (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. Conclusion* Presence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

The aryl hydrocarbon receptor (AhR) is a transcriptional factor that regulates multiple functions following its activation by a variety of ligands, including xenobiotics, natural products, microbiome metabolites, and endogenous molecules. Because of this diversity, the AhR constitutes an exposome receptor. One of its main functions is to regulate several lines of defense against chemical insults and bacterial infections. Indeed, in addition to its well-established detoxication function, it has several functions at physiological barriers, and it plays a critical role in immunomodulation. The AhR is also involved in the development of several organs and their homeostatic maintenance. Its activity depends on the type of ligand and on the time frame of the receptor activation, which can be either sustained or transient, leading in some cases to opposite modes of regulations as illustrated in the regulation of different cancer pathways. The development of selective modulators and their pharmacological characterization are important areas of research. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background: Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosis. Objectives: We aimed to systematically review the experimental evidence (in vivo and in vitro) on the associations between exposure to OCCs and endometriosis-related end points. Methods: A systematic review protocol was developed following the National Toxicology Program /Office of Health Assessment and Translation (NTP/OHAT) framework and managed within a web-based interface. In vivo studies designed to evaluate the impact of OCCs on the onset or progression of endometriosis and proliferation of induced endometriotic lesions were eligible. Eligible in vitro studies included single-cell and co-culture models to evaluate the proliferation, migration, and/or invasion of endometrial cells. We applied the search strings to PubMed, Web of Science, and Scopus®. A final search was performed on 24 June 2020. Assessment of risk of bias and the level of evidence and integration of preevaluated epidemiological evidence was conducted using NTP/OHAT framework Results: Out of 812 total studies, 39 met the predetermined eligibility criteria (15 in vivo, 23 in vitro, and 1 both). Most studies (n=27) tested TCDD and other dioxin-like chemicals. In vivo evidence supported TCDD’s promotion of endometriosis onset and lesion growth. In vitro evidence supported TCDD’s promotion of cell migration and invasion, but there was insufficient evidence for cell proliferation. In vitro evidence further supported the roles of the aryl hydrocarbon receptor and matrix metalloproteinases in mediating steroidogenic disruption and inflammatory responses. Estrogen interactions were found across studies and end points. Conclusion: Based on the integration of a high level of animal evidence with a moderate level of epidemiological evidence, we concluded that TCDD was a known hazard for endometriosis in humans and the conclusion is supported by mechanistic in vitro evidence. Nonetheless, there is need for further research to fill in our gaps in understanding of the relationship between OCCs and their mixtures and endometriosis, beyond the prototypical TCDD. https://doi.org/10.1289/EHP8421

International audience; La formation à l'éthique de la recherche et à l'intégrité scientifique des doctorants au cours de leur formation, toutes spécialités confondues, est obligatoire depuis 2016. Elle est confiée aux écoles doctorales, qui sont libres d'organiser cet enseignement comme elles le souhaitent. Nous avons réalisé une étude auprès de l'ensemble des écoles doctorales de France afin de connaître les modalités de cette formation en 2018. Il apparaît que ces écoles sont bien engagées dans cet enseignement sur l'ensemble du territoire et que la tendance est à son renforcement, ce qui témoigne d'une prise de conscience générale de l'importance de ces sujets pour la recherche de demain.

Background: Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenvironment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenvironment consists, in part, of adipocytes and preadipocytes in which persistent organic pollutants (POPs) can be stored. Objectives: We aimed to test the hypothesis that these two factors (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an extensively studied, toxic POP and the microenvironment) may interact to increase tumor aggressiveness. Methods: We used a co-culture model using BC MCF-7 cells or MDA-MB-231 cells together with hMADS preadipocytes to investigate the contribution of the microenvironment and 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD on BC cells. Global differences were characterized using a high-throughput proteomic assay. Subsequently we measured the BC stem cell–like activity, analyzed the cell morphology, and used a zebrafish larvae model to study the metastatic potential of the BC cells. Results: We found that coexposure to TCDD and preadipocytes modified BC cell properties; moreover, it induced the expression of ALDH1A3, a cancer stem cell marker, and the appearance of giant cancer cells with cell-in-cell structures (CICs), which are associated with malignant metastatic progression, that we demonstrated in vivo. Discussion: The results of our study using BC cell lines co-cultured with preadipocytes and a POP and an in vivo zebrafish model of metastasis suggest that the interactions between BC cells and their microenvironment could affect their invasive or metastatic potential. https://doi.org/10.1289/EHP7102

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter.

The objective of the video article is to present a complete robotic restaging surgery for an early stage endometrioid ovarian cancer developed in an endometrioma in a young patient wishing to preserve her fertility. We demonstrate the entire surgical technique of restaging. Institutional review

International audience; Introduction: Few data have been reported on robot-assisted surgery in elderly. The objectives were to compare feasibility, complication data, and survival of patients under and upper the age of 70 who are managed for endometrial cancer by robot-assisted laparoscopy.Materials and methods: This is a retrospective comparative single-center study including patients treated between January 2007 and December 2016. Patients were divided into 2 groups: less than 70 years and greater than or equal to 70 years. The primary endpoint was the rate of complications. The secondary endpoints were conversion rate and follow-up.Results: 148 patients were included: 86 under 70 (group A) and 62 aged 70 and over (group B). More adhesiolysis was performed in group B (p < .01); the pelvic and para-aortic lymph node dissection rates were not different between both groups (p = .2 and p = .9). The operating times were significantly longer in group B (220.1 vs. 234.4 min, p = .02). The conversion rate was similar between the 2 groups (p = .7). The tumors were endometrioid adenocarcinomas for 77.9 and 66.7% respectively (p = .2), with grade 3 tumors more represented in older patients (24.4% vs. 48.4%, p < .01). There were more tumors at high risk of recurrence after 70 years (33.7 vs. 45.2%, p = .04). No significant difference was found for postoperative complications. There was no difference in overall survival (p = .7) or progression-free survival (p = .2). Undertreated women rate was similar in both groups (p = .1).Conclusion: Robotic surgery appears feasible and reproducible and could bring a benefit and allow optimal surgery without increasing the morbidity in the management of endometrial cancers whatever the age is.

We compared the performance of near-infrared imaging using indocyanine green (ICG) with the radioisotope (ISO) method to detect sentinel lymph nodes (SLNs) in breast cancer, to analyze predictive factors for negative ICG identification. The study included 122 patients who underwent sentinel lymph node biopsy (SLNB) using the combined ISO and ICG technique for primary breast cancer. We assessed the putative association between pathologic/clinical variables and ICG failure to detect SLNs. The ISO identification rate was 96.7% and ICG identification 81.9%. Overweight patients or presence of macrometastasis in SLNB were associated with the risk of ICG failing to detect SLNs (P = 0.02).

Endocervical microglandular hyperplasia (MGH) is a reactive type of glandular lesion that may be confused with endocervical adenocarcinoma from the macroscopic and the colposcopic findings, as well as from a histological. Differential diagnosis is very important. Here, we report a case of a 21 years-old women with a challenging differential diagnosis in the colposcopy and a MGH as histological finding.

Objectives To describe step-by-step the technique of ICG injection and the real-time detection of pelvic Sentinel Lymph Nodes using near-infrared imaging. Methods This is a surgical teaching video demonstrating SLN mapping in uterine cancer using assisted fluorescence imaging. One milliter of Indocyanine green (2,5 mg/ml) is injected in 2 points into the cervix (deeply in the stroma and/or superficially in the submucosa) at 3 and 9 o’clock with a 22G needleunder anesthesia at the beginning of the operation or after set-up of the surgical access. Results We suggest opening first the entire retroperitoneal space along the external iliac vessels and to identify the ureter and the obliterated umbilical artery. This approach allows to observe the early drainage from the cervix through the parametrium by following the dye progression in the channels before any node is taken to ensure that the true draining SLN is identified and not missed. Although the false negative rate may be limited by increasing the number of SLNs sampled, not all detected nodes should be taken but only the first draining node in the channel pathway has to be removed and labeled as SLN. This strategy permits to perform a real SLN-mapping and avoids considering as SLNs non-SLNs which correspond in fact to distal migration of tracer beyond the true SLN.However, in case of truly separate channels which may correspond to distinct pathway, more SLNs should be sample. Conclusions NIR fluorescence ICG demonstrated its ability for real-time intraoperative vizualisation and detection of SLN in early-stage cervical cancer.

Objectives Endocervical microglandular hiperplasia (MGH) is a reactive type of glandular lesion that may be confused with endocervical adenocarcinoma from the macroscopic and the colposcopic findings, as well as from a histological. Differential diagnosis is important. Methods Case report. Patient aged 21 years, with losses smelly and caused metrorrhagia. She has been on oral contraceptives. Examination: exuberant and friable cervix. A budding papillary lesion of the cervix circumferential. Cervix 2–3 cm in diameter, free parameters. Colposcopy with new biopsy confirming florid endocervical microglandular hyperplasia in a context of of endocervicitis. Cytology normal. Oncogenic Papillomavirus positive. Ultrasound: mixed tissue image stretching the endocervix by 35*27*14 mm surrounded by vessels but not vascularized. MRI: atypical image, ulceration. Tumor origin? In view of the very atypical aspect, we propose a conisation and endocervical curettage with a view to diagnosis. Histology of conisation: microglandular cervical hyperplasia associated with subacute and chronic cervicitis. Immunohistochemistre: p16 negative. Results Conclusions MGH incidence is about 15% and generally is found in young women. MGH seems to be associated to the effects of endogenous hormones, pregnancy or to iatrogenic effects of prolonged hormone therapy or contraceptives. But in some stuadies the association between MGH and the use of long-term of hormones is not clear beacuse it can also be found in post-menopausal women with or without a history of hormone replacement therapy. In conisation specimens normally is associated to CIN (Cervical intraepithelial neoplasia) Immunohistochemical markers like p53, CEA, MIBI and Ki67 can be useful for the differential diagnosis if histology is not clear.

Objectives We studied the different risk factors to involvement lymph pelvic node and to recurrence in patients with early cervical cancer in our population. Methods We retrospectively analysed the data from 85 patients with early cervical cancer treated at the European Hospital George Pompidou in Paris between January 2004 and June 2018. Inclusion criteria: patients with cervical cancer stage IA1- IIA. Exclusion criteria: missing or insufficient follow-up data ( The chi-square test (or Fisher’s test if sample size too small) was used to compare qualitative variables. A value of p=0.05 was used as the limit of statistical significance in the parametric analyses NS = no significance. Results Conclusions Many factors for recurrence have been described in patients with cervical cancer. Lymph node involvement is considered the main prognostic factor. Other prognostic factors for recurrence are tumour size, maximum stromal invasion, and presence or absence of lymphovascular space involvement (LVSI) have been evaluated. Different factors had been associated for risk to involvement lymph pelvic nodes: depth of invasion parametrial involvement, lymphatic-vascular space invasion, tumor grade and size of primary tumor. We don´t find any factors associated with the risk of involved nodes. The only factor associated with the risk of recurrence was tumor size.

Objectives The objective of this study was to determine clinical, tumor and surgical factors associated with sucessful bilateral sentinel lymph node mapping (SBM) in early-stage cervical cancer. Methods We performed an ancillary work on the data of two prospective trials on SLN biopsy for FIGO IA-IIA cervical cancer (SENTICOL I & II). Patients having a radical surgery with lymph node dissection were included between 2005 and 2012 from 25 French oncologic centers. Sentinel lymph node (SLN) was detected by a combined labeling technique (blue and isotopic). Results 326 patients were included for analysis: SLNs were identified on at least one side of the pelvis in 308 patients (97.6%) and bilaterally in 278 patients (85.3%). No SLNs were found in 8 patients (2.4%). The mean age was 43 years [22–85 years]. Most patients (88.1%) had IB1 clinical FIGO stage. The majority of patients (71%) had squamous cells carcinoma. Surgeries were mainly performed by mini-invasive approach (296 patients – 90.8%) whereas 30 patients (9.2%) were operated by laparotomy. By multivariate analysis, SBM was associated with minimal invasive approach (ORa= 15.00, 95%CI = [1.24 – 181.63], p = 0.03) and inclusion during the period 2009–2012 (ORa= 14.81, 95%CI = [3.89 – 56.45], p Conclusions A better experience of SLN biopsy technique, minimal invasive approach and patient age

Objectives The purpose of this study was to identify patients with low-risk of parametrial involvement (PI) in early-stage cervical cancer potentially eligible for less radical surgery based on sentinel lymph node (SLN) status. Methods We performed an ancillary analysis of data from two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II). Patients with FIGO IA-IIA cervical cancer treated with radical surgery and lymph node dissection, including SLN biopsy, were identified between 2005 and 2012 from 25 French oncologic centers. Patients who did not undergo radical surgery and patients who had preoperative brachytherapy were excluded. Results Of 211 patients who fullfiled inclusion criteria, 11 patients (5.2%) had a pathological PI and 29 patients (13.7%) had positive SLN. The mean age was 43.2 years [22 – 85]. 160 patients had a radical hysterectomy (75.8%) and 59 a radical trachelectomy (24.2%). 86.1% of patients had stage IB1 disease. There were 68.9% epidermoid carcinomas and 28.6% adenocarcinomas. On multivariate analysis, PI was significantly associated with tumor size ≥ 20 mm at preoperative MRI (ORa = 5.75, 95%IC = [1.17–28.32], p =0.03) and positive sentinel lymph node (ORa = 9.59, 95%IC = [1.13–41.43], p =0.02).Of 114 patients with tumor smaller than 2 cm at preoperative MRI and negative SLN, only one had parametrial involvement (0.9%). Conclusions Patients at low-risk of parametrial involvement may be safely selected with simple criteria. Less radical surgery associated with SLN biopsy may be a promising option for patients with tumor smaller than 2 cm and negative SLN.

Background: Endometriosis is a hormone-dependent gynaecological disease characterised by the presence and growth of endometrial tissues outside of the uterus. There is growing experimental evidence that suggests environmental endocrine disrupting chemicals, specifically organochlorine chemicals (OCCs), may play a role in the pathogenesis of endometriosis, but to date, there are no studies attempting to gather and synthesise the published literature systematically. Objectives: The main objective of this SR is to evaluate the associations between the exposure to OCCs and endometriosis in experimental models (in vivo and in vitro). Methods: The SR framework has been developed following the guidelines established in National Toxicology Program/ Office of Health Assessment and Translation (NTP/OHAT) Handbook for Conducting a Literature-Based Health Assessment, which provides a standardised methodology to implement the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health assessments. The review process will be managed and documented through HAWC, an open-source content management system, to guarantee transparency. Eligibility criteria: Only experimental studies, in vivo, ex vivo or in vitro, exploring associations between controlled exposures to OCCs and endometriosis and related outcomes will be included. Eligible studies will include peer reviewed articles of any publication date which are sources of primary data. Only studies published in English will be considered. Information sources: We will apply the search strings to the scientific literature databases NCBI PubMed, Web of Science and SCOPUS. Manual searches will be performed through the list of references of included articles. Data extraction and synthesis or results: Data will be extracted according to a pre-defined set of forms and synthesised in a narrative report. Given sufficient commensurate data, a meta-analysis may also be performed. Risk of bias: A quality assessment will be performed for in vivo and in vitro studies using the NTP/OHAT Risk of Bias Rating Tool for Human and Animal Studies. Level of evidence rating: Following a comprehensive assessment of the quality of evidence for both in vivo and in vitro studies, a confidence rating will be assigned to the body of literature and subsequently translated into a rating on the level of evidence (high, moderate, low, or inadequate) regarding the research question.Systematic review registration: PROSPERO CRD42018102618. Keywords: Endometriosis, Organochlorine, Dioxins, Endocrine disrupting chemicals, In vivo, In vitro, Systematic review

Meriem Koual, Hind Abbou, Marie Carbonnel, Olivier Picone, Jean-Marc Ayoubi Department of Gynecology and Obstetrics, Hôpital Foch, Suresnes, France Introduction: Preeclampsia constitutes a cause of increased mortality in mothers and fetuses. Screening for promoting factors is essential for adequate prevention in the event of any subsequent pregnancy, and for the adequate follow-up of concerned patients. The aim of the present study was to evaluate the short-term outcome of patients with preeclampsia and to identify possible new factors predisposing them to the disease. Methods: One hundred fifty-five patients having experienced preeclampsia between 2005 and 2010 from the Gynecology and Obstetrics Department of the Foch Hospital (Suresnes, France) were included in the study. All patients had undergone close clinical and standard biological follow-up immediately postpartum and then 3 months later with a reference practitioner. In severe cases, further investigation was carried out by full etiological examination with an assessment of both autoimmune and thrombophilic status. Results: Obesity and gestational diabetes were observed to be major risk factors for preeclampsia, which were found in 46% and 15% of the cases, respectively. The etiological assessment showed abnormalities in 11% of the patients. Impaired thrombophilia was found in 3% of the patients, impaired autoimmune status in 4%, a combination of both abnormalities in only 1% of the patients, and detection of renal abnormalities in 3% of the patients were observed. In the immediate postpartum period, 66% of patients had maintained elevated blood pressure levels, and 66% had proteinuria > 0.3 g/24 hours. At the 3-month postpartum assessment, persisting arterial hypertension was found in 16% of the patients, requiring continuation of antihypertensive therapy, and 22% of the patients had proteinuria over the accepted threshold (0.15 g/24 hours). Conclusion: Patients with preeclampsia have increased cardiovascular risk, necessitating lifestyle measures and long-term follow-up. Etiological assessment must be carried out, systematically aiming at the detection of promoting underlying diseases and adaptation of the management of subsequent pregnancies. Keywords: preeclampsia, postpartum, gestational hypertensive disorders