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Background: Low-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells., Objective: This translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN., Study Design: The expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab., Results: We confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab., Conclusions: Our work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Endometriosis is a complex gynecologic disorder characterized primarily by symptoms of pelvic pain, infertility, and altered quality of life. National and international guidelines highlight the diagnostic difficulties and lack of conclusive diagnostic tools for endometriosis. Furthermore, guidelines are becoming questionable at an increasingly rapid rate as new diagnostic techniques emerge. This work aims to provide a knowledge synthesis of the relevance of various diagnostic tools and to assess areas of improvement of conventional algorithms. MEDLINE and Cochrane Library databases were searched from January 2021 to December 2023 using relevant key words. Articles evaluating the diagnostic relevance and performance of various tools were included and independently reviewed by the authors for eligibility. Included studies were assessed using the GRADE and QUADAS-2 tools. Of the 4204 retrieved articles, 26 were included. While anamnesis and clinical examination do contribute to diagnostic accuracy, their level of evidence and impact on the diagnostic process remains limited. Although imaging techniques are recommended to investigate endometriosis, ultrasonography remains highly operator dependent. Magnetic resonance imaging appears to exhibit higher sensitivities than ultrasound. However, concerns persist with regards to the terminology, anatomical definition of lesions, and accuracies of both ultrasound and magnetic resonance imaging. Recently, several biological markers have been studied and cumulative evidence supports the contribution of noncoding RNAs to the diagnosis of endometriosis. Marginal improvements have been suggested for anamnesis, clinical examination, and imaging examinations. Conversely, some biomarkers, including the saliva microRNA signature for endometriosis, have emerged as diagnostic tools which inspire reflection on the revision of conventional diagnostic algorithms., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: Patients with superficial peritoneal endometriosis (SPE) present with symptoms suggestive of endometriosis but clinical and imaging exams are inconclusive. Consequently, laparoscopy is usually necessary to confirm diagnosis. The present study aimed to evaluate the accuracy of microRNAs (miRNAs) to diagnose patients with SPE from the ENDOmiARN cohort STUDY DESIGN: This prospective study (NCT04728152) included 200 saliva samples obtained between January and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy and/or MRI to confirm the presence of endometriosis. Among the patients with endometriosis, two groups were defined: an SPE phenotype group of patients with peritoneal lesions only, and a non-SPE control group of patients with other endometriosis phenotypes (endometrioma and/or deep endometriosis). Data analysis consisted of two parts: (i) identification of a set of miRNA biomarkers using next-generation sequencing (NGS), and (ii) development of a saliva-based miRNA signature for the SPE phenotype in patients with endometriosis based on a Random Forest (RF) model., Results: Among the 153 patients with confirmed endometriosis, 10.5 % (n = 16) had an SPE phenotype. Of the 2633 known miRNAs, the feature selection method generated a signature of 89 miRNAs of the SPE phenotype. After validation, the best model, representing the most accurate signature had a 100 % sensitivity, specificity, and AUC., Conclusion: This signature could constitute a new diagnostic strategy to detect the SPE phenotype based on a simple biological test and render diagnostic laparoscopy obsolete. PRéCIS: We generated a saliva-based signature to identify patients with superficial peritoneal endometriosis which is the most challenging form of endometriosis to diagnose and which is often either misdiagnosed or requires invasive laparoscopy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality., Design: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based., Methods: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival., Results: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life., Competing Interests: Declaration of competing interest The members of the steering committee, the redactors and the reviewers declare that they have no link of interest that could interfere with this work., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: Low grade serous ovarian carcinoma (LGSOC) accounts for 2.5% of all ovarian carcinoma more affects younger women than high grade serous ovarian carcinoma. Hysterectomy is performed routinely for LGSOC treatment, but fertility sparring surgery (FSS) is feasible for some early stages. Currently, there is no study about uterine involvement in LGSOC. We evaluate uterine involvement in LGSOC patients and aim to identify pre-operative predictive factors., Methods: Retrospective observational study of LGSOC patients treated between January 2000 and May 2022 in the Hospices Civils de Lyon. All cases were viewed, reviewed or approved by an expert pathologist., Results: Among 535 serous ovarian carcinomas, 26 were included. Most patients (73 %) had FIGO III disease. Median OS was 115 months and median PFS was 42 months. Uterine involvement was found in 58 % patients who underwent hysterectomy (14/24), serosal involvement was the most frequent type of involvement (n = 13, 54 %). Myometrial involvement was found in 8 patients (33 %) and was associated with serosal involvement (7/8). Among patients with a macroscopic disease-free uterus during exploratory laparoscopy, 31 % had a microscopic serosal involvement. None patient with presumed early stage (FIGO I) were upstaged due to uterine involvement (serosal or myometrial). In patients with stage FIGO IIII, 72 % of uterine involvement were found. Univariate analysis did not show any predictive factor of myometrial involvement. There was no difference on OS nor PFS between patients with or without myometrial involvement., Conclusions: In early stages LGSOC, FSS may be considered for selected patients. In advanced stages, hysterectomy should be performed routinely, since no predictive factor for uterine involvement were identified., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benoit You: Consulting for MSD, Astra-Zeneca, GSK-TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, Myriad, Menarini, Gilead, EISAI. Christine Rousset-Jablonski: ROCHE – Advisory Board, 2020 (Payment to my institution); Bristol Myers Squibb - Advisory Board, 2020; Theramex – Symposium honoraries, 2021, 2022 (Payment to my institution); Organon – Symposium honoraries, 2021, 2022 (Payment to my institution); Novartis – Symposium honoraries, 2021, 2022 (Payment to my institution). Others authors certify that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The standard treatment for gestational choriocarcinoma is chemotherapy., Objective: To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy., Methods: A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization., Results: Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases., Conclusions: This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients., (© 2024 Published by Elsevier Ltd.)

Light-Non-Aqueous phase liquids (LNAPLs) are important soil contamination sources, and groundwater fluctuations may significantly affect their migration and release. However, the risk assessment remains complex due to the continuous three-phase fluid redistribution caused by water table level variations. Hence, monitoring methods must be improved to integrate better the LNAPL multi-compound and multi-phase aspects tied to the groundwater level dynamics. For this purpose, a lysimetric contaminated soil column (2 m 3 ) combining in-situ monitoring (electrical permittivity, soil moisture, temperature, pH, Eh), direct water and gas sampling and analyses (GC/MS-TQD, μGC) in monitoring well, gas collection chambers, and suction probes) were developed. This experiment assesses in an integrated way how controlled rainfalls and water table fluctuation patterns may affect LNAPL vertical soil saturation distribution and release. Coupling these methods permitted the investigation of the effects of rainwater infiltration and water table level fluctuation on contaminated soil oxygen turnover, LNAPL contaminants' soil distribution and remobilization towards the dissolved and the gaseous phase, and the estimate of the LNAPL source attenuation rate. Hence, 7.5% of the contamination was remobilized towards the dissolved and gaseous phase after 120 days. During the experiment, groundwater level variations were responsible for the free LNAPL soil spreading and trapping, modifying dissolved LNAPL concentrations. Nevertheless, part of the dissolved contamination was rapidly biodegraded, leaving only the most bio-resistant components in water. This result highlights the importance of developing new experimental devices designed to assess the effect of climate-related parameters on LNAPL fate at contaminated sites., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease., Objective: This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management., Study Design: This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022., Results: Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8., Conclusion: Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endometriosis is a chronic and disabling gynecological disease that affects women of reproductive age. Magnetic resonance imaging (MRI) is considered the cornerstone radiological technique for both the diagnosis and management of endometriosis. While MRI offers higher sensitivity compared to ultrasonography, it is prone to false-positive results, leading to decreased specificity. False-positive findings can arise from various T1-hyperintense conditions on fat-suppressed T1-weighted images, resembling endometriotic cystic lesions in different anatomical compartments. These conditions include hemorrhage, hyperproteic content, MRI artifacts, feces, or melanin. Such false positives can have significant implications for patient care, ranging from incorrect diagnoses to unnecessary medical or surgical interventions and subsequent follow-up. To address these challenges, this educational review aims to provide radiologists with comprehensive knowledge about MRI criteria, potential pitfalls, and differential diagnoses, ultimately reducing false-positive results related to T1-hyperintense abnormalities.Critical relevance statementMRI has a 10% false-positive rate, leading to misdiagnosis. T1-hyperintense lesions, observed in the three phenotypes of pelvic endometriosis, can also be seen in various other causes, mainly caused by hemorrhages, high protein concentrations, and artifacts.Key points• MRI in endometriosis has a 10% false-positive rate, leading to potential misdiagnosis.• Pelvic endometriosis lesions can exhibit T1-hyperintensity across their three phenotypes.• A definitive diagnosis of a T1-hyperintense endometriotic lesion is crucial for patient management.• Hemorrhages, high protein concentrations, lipids, and artifacts are the main sources of T1-hyperintense mimickers., (© 2024. The Author(s).)

Objectives: To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival., Methods: We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available., Results: Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months)., Conclusion: In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Today, most women with gestational trophoblastic disease (GTD) can expect to be cured, particularly if they live in middle- to high-income countries with access to GTD centres. In contrast, countries lacking organized GTD care achieve lower survival rates., Objectives: The aim of the study was to review and consider some of the successes and areas for improvement in GTD care that have been achieved through national and international collaborations., Methods: The authors searched PubMed and used their own knowledge of working nationally and internationally in GTD to write this review., Conclusions: The establishment of expert centres and national systems for managing GTD is associated with the best disease outcomes. National and in particular international collaboration is most likely to result in further optimisation of management protocols and outcomes., Outlook: It remains crucial for countries lacking GTD centres to try to establish such facilities with support from national agencies and international expert societies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: In contrast to miRNA expression, little attention has been given to piwiRNA (piRNA) expression among endometriosis patients. The aim of the present study was to explore the human piRNAome and to investigate a potential piRNA saliva-based diagnostic signature for endometriosis., Methods: Data from the prospective "ENDOmiRNA" study (ClinicalTrials.gov Identifier: NCT04728152) were used. Saliva samples from 200 patients were analyzed in order to evaluate human piRNA expression using the piRNA bank. Next Generation Sequencing (NGS), barcoding of unique molecular identifiers and both Artificial Intelligence (AI) and machine learning (ML) were used. For each piRNA, sensitivity, specificity, and ROC AUC values were calculated for the diagnosis of endometriosis., Results: 201 piRNAs were identified, none had an AUC ≥ 0.70, and only three piRNAs (piR-004153, piR001918, piR-020401) had an AUC between ≥ 0.6 and < 0.70. Seven were differentially expressed: piR-004153, piR-001918, piR-020401, piR-012864, piR-017716, piR-020326 and piR-016904. The respective correlation and accuracy to diagnose endometriosis according to the F1-score, sensitivity, specificity, and AUC ranged from 0 to 0.862 %, 0-0.961 %, 0.085-1, and 0.425-0.618. A correlation was observed between the patients' age (≥35 years) and piR-004153 (p = 0.002) and piR-017716 (p = 0.030). Among the 201 piRNAs, four were differentially expressed in patients with and without hormonal treatment: piR-004153 (p = 0.015), piR-020401 (p = 0.001), piR-012864 (p = 0.036) and piR-017716 (p = 0.009)., Conclusion: Our results support the link between piRNAs and endometriosis physiopathology and establish its utility as a potential diagnostic biomarker using saliva samples. Per se, piRNA expression should be analyzed along with the clinical status of a patient., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Lipomodelling (LM) is an increasingly used technique to reconstruct or correct an aesthetic defect linked to a loss of substance. In France, the Haute Autorité de santé (HAS) published recommendations in 2015 and 2020 concerning the conditions of use of LM on the treated and contralateral breast. These appear to be inconsistently followed., Methods: Twelve members of the Senology Commission of the Collège national des gynécologues-obstétriciens français (French College of Gynecologists and Obstetricians) reviewed the carcinological safety of LM and the clinical and radiological follow-up of patients after breast cancer surgery, based on French and international recommendations and a review of the literature. The bibliographic search was conducted via Medline from 2015 to 2022, selecting articles in French and English and applying PRISMA guidelines., Results: A total of 14 studies on the oncological safety of LM, 5 studies on follow-up and 7 guidelines were retained. The 14 studies (6 retrospective, 2 prospective and 6 meta-analyses) had heterogeneous inclusion criteria and variable follow-up, ranging from 38 to 120 months. Most have shown no increased risk of locoregional or distant recurrence after LM. A retrospective case-control study (464 LMs and 3100 controls) showed, in patients who had no recurrence at 80 months, a subsequent reduction in recurrence-free survival after LM in cases of luminal A cancer, highlighting the number of lost to follow-up (more than 2/3 of luminal A cancers). About follow-up after LM, the 5 series showed the high frequency after LM of clinical mass and radiological images (in ¼ of cases), most often corresponding to cytosteatonecrosis. Most of the guidelines highlighted the uncertainties concerning oncological safety of LM, due to the lack of prospective data and long-term follow-up., Discussion and Perspectives: The members of the Senology Commission agree with the conclusions of the HAS working group, in particular by advising against LM "without cautionary periods", excessively, or in cases of high risk of relapse, and recommend clear, detailed information to patients before undergoing LM, and the need for postoperative follow-up. The creation of a national registry could address most questions regarding both the oncological safety of this procedure and the modalities of patient follow-up., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Liver metastases of gestational trophoblastic neoplasia (GTN) are rare, but associated with poor prognosis. The additional concomitant presence of brain or intra-abdominal metastases, with liver metastases has been described as worsening factors, but the literature on this topic is reduced., Objective: To estimate the overall mortality, specific hepatic morbidity, and mortality, and to identify prognostic factors for patients with GTN and liver metastases., Method: The medical records of 26 GTN patients with liver metastases registered in the French Center for Trophoblastic Diseases and treated between November 1999 and December 2019 were reviewed. Overall survival was described using Kaplan-Meier estimates. Prognostic factors were identified using univariate and multivariate Cox analyses., Results: The 5-year overall survival rate was 60.7% for all patients with liver metastasis. The survival rate was higher in patients who achieved complete remission after first-line chemotherapy than in those who did not (100% vs 20%, p = 0.001). The only factor independently associated with prognosis was the presence of 6 or more liver metastases (5-year survival, 16.7% vs. 82.4% otherwise; HR =11.1, 95%CI, 2.3-53.1; p = 0.003). None of the five patients with a single liver metastasis died., Conclusion: GTN with liver metastasis is very rare (1.6%). The prognosis of patients seems to be improving. The results of this study are also reassuring for patients with complete remission after first-line combination chemotherapy, as well as for those with a single liver metastasis., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

BACKGROUND: The discovery of a saliva-based micro–ribonucleic acid (miRNA) signature for endometriosis in 2022 opened up new perspectives for early and noninvasive diagnosis of the disease. The 109-miRNA saliva signature is the product of miRNA biomarkers and artificial intelligence (AI) modeling. We designed a multicenter study to provide external validation of its diagnostic accuracy. We present here an interim analysis. METHODS: The first 200 patients included in the multicenter prospective ENDOmiRNA Saliva Test study (NCT05244668) were included for interim analysis. The study population comprised women from 18 to 43 years of age with a formal diagnosis of endometriosis or with suspected endometriosis. Epidemiologic, clinical, and saliva sequencing data were collected between November 2021 and March 2022. Genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) was performed, and a random forest algorithm was used to assess the diagnostic accuracy. RESULTS: In this interim analysis of the external validation cohort, with a population prevalence of 79.5%, the 109-miRNA saliva diagnostic signature for endometriosis had a sensitivity of 96.2% (95% confidence interval [CI], 93.7 to 97.3%), specificity of 95.1% (95% CI, 85.2 to 99.1%), positive predictive value of 95.1% (95% CI, 85.2 to 99.1%), negative predictive value of 86.7% (95% CI, 77.6 to 90.3%), positive likelihood ratio of 19.7 (95% CI, 6.3 to 108.8), negative likelihood ratio of 0.04 (95% CI, 0.03 to 0.07), and area under the receiver operating characteristic curve of 0.96 (95% CI, 0.92 to 0.98). CONCLUSIONS: The use of NGS and AI in the sequencing and analysis of miRNA provided a saliva-based miRNA signature for endometriosis. Our interim analysis of a prospective multicenter external validation study provides support for its ongoing investigation as a diagnostic tool. (Funded by Ziwig and the Conseil Régional d’Ile de France [Grant EX024087]; ClinicalTrials.gov number, NCT05244668.)

Background: A higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF)., Methods: We conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology., Results: We included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients., Conclusion: Transplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: The purpose of this consensus article was to develop guidelines by a focused panel of experts to elaborate a lexicon of image interpretation, and a standardized region-based reporting of deep infiltrating endometriosis (DIE) with magnetic resonance imaging (MRI)., Materials and Methods: Evidence-based data and expert opinion were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts scoring of pelvic compartment delineation and reporting template were collected; responses were analyzed and classified as "RECOMMENDED" versus "NOT RECOMMENDED" (when ≥ 80% consensus among experts) or uncertain (when < 80% consensus among experts)., Results: Consensus regarding pelvic compartment delineation and DIE reporting was attained using the RAND-UCLA Appropriateness Method. The pelvis was divided in nine compartments and extrapelvic lesions were assigned to an additional (tenth) compartment. A consensus was also reached for each structure attributed to a compartment and each reporting template item among the experts. No consensus was reached for a normal aspect of uterosacral ligament, but a consensus was reached for an unequivocal involvement leading to a positive diagnosis and an equivocal involvement leading to uncertain diagnosis. Tailored MRI lexicon and standardized region-based report were proposed., Conclusion: These consensus recommendations should be used as a guide for DIE reporting and staging with MRI. Standardized MRI compartment-based structured reporting is recommended to enable consistent accuracy and help select the best therapeutic approach., Competing Interests: Declaration of Competing Interest Pascal Rousset declares consultancies for ZIWIG and EDAP TMS France. François Golfier declares consultancies for ZIWIG. The other authors have no competing interests to disclose., (Copyright © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Ovarian tumors are the most frequent adnexal mass, raising diagnostic and therapeutic issues linked to a large spectrum of tumors, with a continuum from benign to malignant. Thus far, none of the available diagnostic tools have proven efficient in deciding strategy, and no consensus exists on the best strategy between "single test", "dual testing", "sequential testing", "multiple testing options" and "no testing". In addition, there is a need for prognostic tools such as biological markers of recurrence and theragnostic tools to detect women not responding to chemotherapy in order to adapt therapies. Non-coding RNAs are classified as small or long based on their nucleotide count. Non-coding RNAs have multiple biological functions such as a role in tumorigenesis, gene regulation and genome protection. These ncRNAs emerge as new potential tools to differentiate benign from malignant tumors and to evaluate prognostic and theragnostic factors. In the specific setting of ovarian tumors, the goal of the present work is to offer an insight into the contribution of biofluid non-coding RNAs (ncRNA) expression., Competing Interests: The authors declare they have no conflict of interest.

Risk-reducing salpingo-oophorectomy is the gold standard for the prophylaxis of ovarian cancer in high-risk women. Due to significant adverse effects, 20-30% of women delay or refuse early oophorectomy. This prospective pilot study (NCT01608074) aimed to assess the efficacy of radical fimbriectomy followed by a delayed oophorectomy in preventing ovarian and pelvic invasive cancer (the primary endpoint) and to evaluate the safety of both procedures. The key eligibility criteria were pre-menopausal women ≥35 years with a high risk of ovarian cancer who refused a risk-reducing salpingo-oophorectomy. All the surgical specimens were subjected to the SEE-FIM protocol. From January 2012 to October 2014, 121 patients underwent RF, with 51 in an ambulatory setting. Occult neoplasia was found in two cases, with one tubal high-grade serous ovarian carcinoma. Two patients experienced grade 1 intraoperative complications. No early or delayed grade ≥3 post-operative complications occurred. After 7.3 years of median follow-up, no cases of pelvic invasive cancer have been noted. Three of the fifty-two patients developed de novo breast cancer. One BRCA1-mutated woman delivered twins safely. Twenty-five patients underwent menopause, including fifteen who had received chemotherapy for breast cancer, and twenty-three underwent menopause before the delayed oophorectomy, while two did not undergo a delayed oophorectomy at all. Overall, 46 women underwent a delayed oophorectomy. No abnormalities were found in any delayed oophorectomy specimens. Radical fimbriectomy followed by delayed oophorectomy appears to be a safe and well-tolerated risk-reducing approach, which avoids early menopause for patients with a high risk of breast and ovarian cancer.

Research Question: Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome?, Design: The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model., Results: Among the 153 patients diagnosed with endometriosis, 24% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ∼13.7 M to ∼39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%., Conclusion: A saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis., (Copyright © 2022 Reproductive Healthcare Ltd. All rights reserved.)

Purpose: There is a need for innovative treatments in women with gestational trophoblastic tumors (GTT) resistant to chemotherapy. The TROPHIMMUN trial assessed the efficacy of avelumab in patients with resistance to single-agent chemotherapy (cohort A), or to polychemotherapy (cohort B). Cohort B outcomes are reported here., Methods: In the cohort B of this phase 2 multicenter trial (NCT03135769), women with GTT progressing after polychemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. The primary endpoint was the rate of hCG normalization enabling treatment discontinuation (2-stage Simon design)., Results: Between February 2017 and August 2020, 7 patients were enrolled. Median age was 37 years (range: 29-47); disease stage was I or III in 42.9% and 57.1%; FIGO score was 9-10 in 28.6%, 11 in 28.6%, and 16 in 14.3%, respectively. Median follow-up was 18.2 months. One patient (14.3%) experienced hCG normalization enabling treatment discontinuation. However, resistance to avelumab was observed in the remaining 6 patients (85.7%). The cohort B was stopped for futility. Grade 1-2 treatment-related adverse events occurred in 57.1%, most commonly fatigue (42.9%), nausea, diarrhea, infusion-related reaction, muscle pains, dry eyes (each 14.3%). The median resistance-free survival was 1.4 months (95% CI 0.7-5.3)., Conclusions: Although avelumab is active in patients with single-agent chemotherapy-resistant GTT (cohort A), it was associated with limited efficacy in patients with resistance to polychemotherapy (cohort B). The prognosis of patients with polychemotherapy resistance remains poor, and innovative immunotherapy-based therapeutic combinations are needed., Competing Interests: Declaration of Competing Interest No conflicts of interest to dissclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Gestational trophoblastic diseases derived from the chorionic-type intermediate trophoblast include benign placental site nodule (PSN) and malignant epithelioid trophoblastic tumor (ETT). Among PSNs, the World Health Organization classification introduced a new entity named atypical placental site nodule (APSN), corresponding to an ETT precursor, for which diagnostic criteria remain unclear, leading to a risk of overdiagnosis and difficulties in patient management. We retrospectively studied 8 PSNs, 7 APSNs, and 8 ETTs to better characterize this new entity and performed immunohistochemical analysis (p63, human placental lactogen, Cyclin E, and Ki67), transcriptional analysis using the NanoString method to quantify the expression of 760 genes involved in the main tumorigenesis pathways, and RNA sequencing to identify fusion transcripts. The immunohistochemical analysis did not reveal any significant difference in Cyclin E expression among the 3 groups (P = .476), whereas the Ki67 index was significantly (P < .001) higher in ETT samples than in APSN and PSN samples. None of the APSN samples harbored the LPCAT1::TERT fusion transcripts, in contrast to 1 of 6 ETT samples, as previously described in 2 of 3 ETT samples. The transcriptomic analysis allowed robust clustering of ETTs distinct from the APSN/PSN group but failed to differentiate APSNs from PSNs. Indeed, only 7 genes were differentially expressed between PSN and APSN samples; CCL19 upregulation and EPCAM downregulation were the most distinguishing features of APSNs. In contrast, 80 genes differentiated ETTs from APSNs, establishing a molecular signature for ETT. Gene set analysis identified significant enrichments in the DNA damage repair, immortality and stemness, and cell cycle signaling pathways when comparing ETTs and APSNs. These results suggested that APSN might not represent a distinct entity but rather a transitional stage between PSN and ETT. RNA sequencing and the transcriptional signature of ETT described herein could serve as triage for APSN from curettage or biopsy material, enabling the identification of cases that need further clinical investigations., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: This study assesses the effectiveness of cervicoisthmic cerclage on the live birth rate, measured before and after performing this cerclage in a series of 62 patients with a history of late miscarriage and/or premature delivery., Study Design: All patients who underwent cervicoisthmic cerclage in one of the 3 university hospitals of the Hospices Civils de Lyon, between January 1, 2010, and April 1, 2019, and with a history of at least one late miscarriage or spontaneous premature birth, were included. Obstetrical and neonatal data for all pregnancies before and after cervicoisthmic cerclage were collected from medical records, completed by a phone call to patients in case of missing data., Results: We included 62 patients with a total of 224 pregnancies before and 95 pregnancies after cervicoisthmic cerclage. Forty-one (66%) cerclages were performed vaginally, 12 (19%) by laparotomy and 9 (15%) by laparoscopy. The live birth rate among all pregnancies evolving beyond 14 weeks was 23% before and 86% after cerclage (p < 0.01). The rate of delivery beyond 32 weeks was 13% before and 81% after cerclage, with a median term of delivery of 21 weeks and 37 weeks respectively. Twenty-two (35%) patients had at least one live birth before cerclage and 43 (69%) patients after cerclage. Five (8%) postoperative complications occurred (2 grade I, 2 grade II and 1 grade III)., Conclusion: The markedly high live birth rate when compared to before the cerclage strongly suggests a major role for the technique of cervicoisthmic cerclage in patients with a heavy obstetrical history., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Spontaneous hemoperitoneum in pregnancy (SHiP) is a complication of endometriosis. We describe the clinical characteristics and outcomes of mother and fetus in 11 new cases of SHiP with endometriosis and 43 cases reported in the literature since 1995., Material and Methods: The 60 maternity hospitals in the Auvergne-Rhône-Alpes region in France were contacted to identify cases of SHiP associated with endometriosis. In parallel, a systematic review of the literature used the PRISMA chart to report published cases., Results: Fifty-four cases of SHIP associated with endometriosis are presented. Twenty-four patients (44%) conceived with assisted reproductive techniques. Hemoperitoneum occurred before delivery in 47/54 cases (87%).The average gestational age of occurrence was 27 weeks (13 weeks to 40+6 weeks). An hypovolemic shock was present in 24/51 (47%) of patients. Forty-six women (85%) were treated by laparotomy, 5 (9%) by laparoscopy, 2 (2%) by interventional radiology. The hemorrhage site was in the mediolateral compartment of the pelvis in 29 cases (54%), corresponding to bleeding from vessels in the broad ligament in 24/29 (83%) of these cases. The mean estimated blood loss was 1957 mL (150-7500 mL). Emergency peripartum hysterectomy was required in 3/54 cases (6%). There were no maternal deaths. The average gestational age at birth was 30 weeks (13+2 weeks to 42 weeks). The fetus died in 19/64 cases (30%)., Conclusion: SHiP is an underestimated potentially fatal complication of endometriosis. Maternal salvage by emergency laparotomy is usually required to identify and treat the bleeding site. Fetal prognosis remains poor., Competing Interests: Declarations of Competing Interest none., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction and Hypothesis: We assessed 3-year anatomic and functional results using synthetic glue to fix mesh in laparoscopic sacrocolpopexy., Methods: Prospective multicenter cohort study in three academic urogynecology departments. Seventy consecutive patients with stage ≥ 3 POP-Q (Pelvic Organ Prolapse Quantification) anterior and/or apical prolapse underwent laparoscopic sacrocolpopexy using synthetic surgical glue to fix anterior and posterior meshes to the vagina. Patients were followed up at 1, 2 and 3 years. Primary outcome was anterior and apical anatomic success (POP-Q stage ≤ 1) at 3 years. Secondary outcomes comprised functional results (international quality of life and sexuality scales), mesh-related morbidity and urinary incontinence at 3 years., Results: Mean age was 56.7 ± 1.2 years. Mean follow-up was 43 months. Anterior compartment anatomic success rate was 87% at 2 years (Ba, -2.4 cm; p < 0.0001) and 86.5% at 3 years (Ba, -2.3 cm; p < 0.0001); apical success was 96.3% at 2 years (C, -6.8 cm; p < 0.0001) and 97.3% at 3 years (C, -6.5 cm; p < 0.0001). All quality-of-life scores improved significantly and lastingly at 3 years: PFDI-20, PFIQ-7 and PISQ-12, respectively, p < 0.0001, p < 0.0001 and p = 0.01. There was one case of vaginal mesh exposure at 3 years (2.8%) and five of mesh shrinkage at 1 year (7.8%), none at 2 years and two at 3 years (5.4%). Urinary incontinence rate was 29.7% at 1 year, 14.8% at 2 years and 11.1% at 3 years., Conclusion: Vaginal mesh adhesive in laparoscopic sacrocolpopexy remained effective at 3 years, with excellent tolerance and no specific complications. Anatomic and functional results were good and enduring in terms of both anterior and apical correction., (© 2021. The International Urogynecological Association.)

The aim of our study was to describe the bioinformatics approach to analyze miRNome with Next Generation Sequencing (NGS) of 200 plasma samples from patients with and without endometriosis. Patients were prospectively included in the ENDO-miRNA study that selected patients with pelvic pain suggestive of endometriosis. miRNA sequencing was performed using an Novaseq6000 sequencer (Illumina, San Diego, CA, USA). Small RNA-seq of 200 plasma samples yielded ~4228 M raw sequencing reads. A total of 2633 miRNAs were found differentially expressed. Among them, 8.6% ( n = 229) were up- or downregulated. For these 229 miRNAs, the F1-score, sensitivity, specificity, and AUC ranged from 0-88.2%, 0-99.4%, 4.3-100%, and 41.5-68%, respectively. Utilizing the combined bioinformatic and NGS approach, a specific and broad panel of miRNAs was detected as being potentially suitable for building a blood signature of endometriosis.

Objective: This study aimed at assessing perioperative results of robot-assisted laparoscopy (RAL) in the context of deep infiltrating endometriosis (DIE)., Methods: This retrospective French multicentric study included all patients with DIE who underwent surgical treatment managed by RAL (Da Vinci® System). From November 2008 to June 2019, patients were included in a single European database, in Robotic Assisted Laparoscopic Gynecologic Surgery, with Society of European Robotic Gynecological Surgery collaboration. Patients had different DIE sites as follows: gynecological, urological, or digestive, or combinations of these. Surgical procedures and perioperative complications were evaluated. To assess complications, patients were divided into the following four groups according to surgical procedure and DIE site: gynecological only; gynecological and urological; gynecological and digestive; and gynecological, urological, and digestive., Results: A total of 460 patients treated at one of eight health-care facilities from November 2008 to June 2019 were included. Median operative time was 245 min (IQR 186-320), surgeon console time was 138 ± 75 min and estimated blood loss was 70.0 mL ± 107 mL. Among this patient sample, 42.1% had a multidisciplinary surgical approach with a digestive or urology surgeon in addition to gynecology surgeon (25.5% and 16.6% of cases, respectively). Among those with intraoperative complications (n = 25, 5.4%) were primarily conversion to laparotomy (n = 6, 2.0%), transfusion (n = 2, 0.6%), and organ wounds (n = 8, 1.7%). Overall, 5.6% had severe postoperative complications (Clavien-Dindo classification ≥ Grade 3)., Conclusion: This is among the largest published series addressing RAL for DIE. Interest in this procedure appears promising, with no observed increases in blood loss or in peri- or post-operative complications. DIE laparoscopic surgery can require complex surgical procedures performed by multidisciplinary surgical teams. Thus, it may be one of the best candidates for RAL within gynecology surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The exceptional health situation related to the Coronavirus 2019 (COVID-19) pandemic has required an in-depth and immediate reorganisation of gynaecological cancer care. The main objective was to assess the psychological impact of such treatment modifications during the lockdown period for gynaecological and breast cancer patients., Patients and Methods: A multicentre prospective study was conducted in three university gynaecological cancer wards (Hospices Civils de Lyon, France) during the French first lockdown (16th March to 11th May 2020). All patients with non-metastatic breast cancer or gynaecological cancer were included. Data was collected regarding treatment modifications (delay, cancellation, change of therapeutic plan). The psychological impact of treatment modifications during and after the lockdown was assessed by validated questionnaires (SF-12, EORTC-QLQ-C30, HADS)., Results: A total of 205 consecutive patients were included, aged 60.5 ± 1.0 years. Seven patients (3.4%) presented a SARS-CoV-2 infection, and two patients died. Treatment was maintained for 122 (59.5%) patients, postponed for 72 (35.1%) and cancelled for 11 (5.4%). During the lockdown, 35/118 (29.7%) patients suffered from confirmed anxiety and the mean fatigue-EORTC score was 48.00 ± 2.51; it was 38.64 ± 2.33 (p = 0.02) after the lockdown. After the lockdown and compared to the lockdown period, the mental SF-12 score and overall health status EORTC score were significantly higher (45.03 ± 1.06 vs 41.71 ± 1.15, p = 0.02 and 64.58 ± 1.66 vs 57.44 ± 2.02, p = 0.0007, respectively). The number of confirmed-anxiety cases was significantly higher amongst patients for whom treatment was delayed or cancelled (40.5% vs 23.7%, p = 0.04)., Conclusion: This study quantified the treatment modifications of gynaecological cancer patients during the COVID-19 lockdown and revealed a poorer psychological state and quality of life during this period, even for patients whose treatment plan was not actually modified. Anxiety was more significant in patients with a delayed or cancelled treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objective: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation., Design: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted., Methods: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities., Results: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±)., Conclusion: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the value of performing a risk-reducting mastectomy (RRM) in the absence of a deleterious variant of a breast cancer susceptibility gene, in 4 clinical situations at risk of breast cancer., Design: The CNGOF Commission of Senology, composed of 26 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The Commission of Senology adhered to the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted., Methods: The Commission of Senology considered 8 questions on 4 topics, focusing on histological, familial (no identified genetic abnormality), radiological (of unrecognized cancer), and radiation (history of Hodgkin's disease) risk. For each situation, it was determined whether performing RRM compared with surveillance would decrease the risk of developing breast cancer and/or increase survival., Results: The Commission of Senology synthesis and application of the GRADE method resulted in 11 recommendations, 6 with a high level of evidence (GRADE 1±) and 5 with a low level of evidence (GRADE 2±)., Conclusion: There was significant agreement among the Commission of Senology members on recommendations to improve practice for performing or not performing RRM in the clinical setting., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The intergovernmental panel on climate change (IPCC) predicts significant changes in precipitation patterns, an increase in temperature, and groundwater level variations by 2100. These changes are expected to alter light non-aqueous phase liquid (LNAPL) impacts since groundwater level fluctuations and temperature are known to influence both the mobility and release of LNAPL compounds to air and groundwater. Knowledge of these potential effects is currently dispersed in the literature, hindering a clear vision of the processes at play. This review aims to synthesize and discuss the possible effects of the increase in temperature and groundwater level fluctuations on the behavior of LNAPL and its components in a climate change context. In summary, a higher amplitude of groundwater table variations and higher temperatures will probably increase biodegradation processes, the LNAPL mobility, and spreading across the smear zone, favoring the release of LNAPL compounds to the atmosphere and groundwater but decreasing the LNAPL mass and its longevity. Outcomes will, nevertheless, vary greatly across arid, cold, or humid coastal environments, where different effects of climate change are expected. The effects of the climate change factors linked to soil heterogeneities, local conditions, and weathering processes will govern LNAPL behavior and need to be further clarified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Endometriosis diagnosis constitutes a considerable economic burden for the healthcare system with diagnostic tools often inconclusive with insufficient accuracy. We sought to analyze the human miRNAome to define a saliva-based diagnostic miRNA signature for endometriosis., Methods: We performed a prospective ENDO-miRNA study involving 200 saliva samples obtained from 200 women with chronic pelvic pain suggestive of endometriosis collected between January and June 2021. The study consisted of two parts: (i) identification of a biomarker based on genome-wide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) and (ii) development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a Random Forest algorithm., Results: Among the 200 patients, 76.5% (n = 153) were diagnosed with endometriosis and 23.5% (n = 47) without (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). Quantification of the filtered reads and identification of known miRNAs yielded ~190 M sequences that were mapped to 2561 known miRNAs. Of the 2561 known miRNAs, the feature selection with Random Forest algorithm generated after internally cross validation a saliva signature of endometriosis composed of 109 miRNAs. The respective sensitivity, specificity, and AUC for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%., Conclusions: The ENDO-miRNA study is the first prospective study to report a saliva-based diagnostic miRNA signature for endometriosis. This could contribute to improving early diagnosis by means of a non-invasive tool easily available in any healthcare system.

Endometriosis-a systemic and chronic condition occurring in women of childbearing age-is a highly enigmatic disease with unresolved questions. While multiple biomarkers, genomic analysis, questionnaires, and imaging techniques have been advocated as screening and triage tests for endometriosis to replace diagnostic laparoscopy, none have been implemented routinely in clinical practice. We investigated the use of machine learning algorithms (MLA) in the diagnosis and screening of endometriosis based on 16 key clinical and patient-based symptom features. The sensitivity, specificity, F1-score and AUCs of the MLA to diagnose endometriosis in the training and validation sets varied from 0.82 to 1, 0-0.8, 0-0.88, 0.5-0.89, and from 0.91 to 0.95, 0.66-0.92, 0.77-0.92, respectively. Our data suggest that MLA could be a promising screening test for general practitioners, gynecologists, and other front-line health care providers. Introducing MLA in this setting represents a paradigm change in clinical practice as it could replace diagnostic laparoscopy. Furthermore, this patient-based screening tool empowers patients with endometriosis to self-identify potential symptoms and initiate dialogue with physicians about diagnosis and treatment, and hence contribute to shared decision making., (© 2022. The Author(s).)

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., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: To provide guidelines from the French College of Obstetricians and Gynecologists (CNGOF), based on the best currently available evidence, for the prophylactic procedures associated with gynecological surgery for benign disease such as superficial endometriosis lesions and adhesions., Methods: The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade that reflects the quality of evidence (QE) (clinical practice guidelines)., Results: Endometriosis and pelvic pain Superficial endometriosis can be entirely asymptomatic. Surgical treatment of asymptomatic superficial peritoneal endometriosis is not recommended in women of childbearing age for the prevention of pelvic pain, especially in case of proximity to noble organs (e.g., the ureters, rectum and sigmoid, and ovaries in nulligravida) as there is no evidence that the disease will progress to become symptomatic (low level of evidence). In case of accidental discovery of superficial endometriosis in women of childbearing age with pelvic pain, it is recommended that the lesions are excised, if surgically accessible. Removal of superficial endometriosis lesions in patients with painful symptoms improves quality of life and pain (low level of evidence). Endometriosis and infertility It appears that women with isolated superficial endometriosis diagnosed by laparoscopy with histological confirmation have a significantly higher incidence of primary infertility than patients without endometriosis. However, there is no data regarding the impact of treatment of these lesions on the fertility in these women or on the natural course of their disease (low level of evidence). It is recommended that excision is performed rather than monopolar coagulation of superficial endometriosis lesions in infertile women, as this results in a higher spontaneous pregnancy rate (low level of evidence). Adhesions and pelvic pain There is limited data in the literature regarding the benefit of performing systematic adhesiolysis during laparoscopy to prevent pelvic pain when incidental pelvic adhesions are discovered. For patients with pelvic pain, it is probably better not to perform adhesiolysis to prevent pelvic pain, although this can be decided on a case-by-case basis depending on the extent of the adhesions, the topography, and the type of surgery considered (low level of evidence). For asymptomatic patients, it is recommended not to perform adhesiolysis to prevent pelvic pain due to the lack of clear efficacy both short- or long-term and due to the increased risk of surgical injuries (low level of evidence). Adhesions and infertility There is limited data in the literature regarding the potential benefit of performing systematic adhesiolysis when there is an incidental discovery of pelvic adhesions during laparoscopy to prevent infertility. For infertile women, in the event of fortuitous discovery of adhesions at laparoscopy, it is probably better not to perform complex adhesiolysis. Only adhesiolysis of tubo-ovarian adhesions that are minimal or slight in terms of their extension and/or their nature may be useful to improve the chances of spontaneous pregnancy. However, it remains to be decided on a case-by-case basis depending on other potential causes of infertility (low level of evidence). For women without known infertility issues, it is probably better not to perform systematic adhesiolysis in order to improve their pregnancy chances, considering the balance between the unknown benefit and the risks of complications inherent to surgery (low level of evidence)., Conclusion: Further investigations are needed in order to increase the quality of management regarding associated interventions such as the treatment of superficial endometriosis or adhesions performed during a gynecologic surgical procedure and, thereby, bolster these recommendations., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To provide guidelines from the French College of Obstetricians and Gynaecologists (CNGOF), based on the best evidence available, concerning the impact of endometrial destruction on bleeding and endometrial cancer risk reduction in patients candidates for operative hysteroscopy., Methods: Recommendations were made according to AGREE II and the GRADE® (Grading of Recommendations Assessment, Development and Evaluation) systems to determine separately the quality of evidence (QE) and in the level of recommendation., Results: In a retrospective study comparing the incidence of endometrial cancer in 4776 patients with menorrhagia treated with endometrial destruction vs 229 945 patients with a medical treatment. There was a non-significant reduced risk of developing endometrial cancer (HR, 0.45; 95% CI, 0.15-1.40; p = .17). In premenopausal women, five studies compared the incidence of endometrial cancer in patients treated with endometrial ablation/destruction (EA/D) to the incidence of endometrial cancer in a comparable population of women from national registers, all of which show reduced risk of endometrial cancer after endometrectomy. In case of menopausal metrorrhagia, the prevalence of endometrial cancer is 9%, by analogy with the results found in premenopausal patients, the combination of endometrial ablation during operative hysteroscopy seems justified. In a retrospective cohort of 177 non-menopausal patients treated with myomectomy for metrorrhagia and/or menorrhagia, a significantly better control of bleeding at 12 months was found when myomectomy was combined with endometrectomy using roller-ball (OR: 0.18 [95% Cl 0.05-0.63]; p = 0.003)., Conclusion: In premenopausal women with heavy menstrual bleeding, when an operative hysteroscopy is performed, it is recommended to propose an endometrial ablation/destruction in order to prevent the risk of endometrial cancer, (QE3) and to prevent recurrence of bleeding (QE2). In menopausal women, it is probably recommended to also perform an endometrial ablation/destruction in case of operative hysteroscopy in order to prevent the risk of endometrial cancer (QE1)., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To draw up recommendations on the use of prophylactic gynecologic procedures during surgery for other indications., Design: A consensus panel of 19 experts was convened. A formal conflict of interest policy was established at the onset of the process and applied throughout. The entire study was performed independently without funding from pharmaceutical companies or medical device manufacturers. The panel applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate the quality of evidence on which the recommendations were based. The authors were advised against making strong recommendations in the presence of low-quality evidence. Some recommendations were ungraded., Methods: The panel studied 22 key questions on seven prophylactic procedures: 1) salpingectomy, 2) fimbriectomy, 3) salpingo-oophorectomy, 4) ablation of peritoneal endometriosis, 5) adhesiolysis, 6) endometrial excision or ablation, and 7) cervical ablation., Results: The literature search and application of the GRADE system resulted in 34 recommendations. Six were supported by high-quality evidence (GRADE 1+/-) and 28 by low-quality evidence (GRADE 2+/-). Recommendations on two questions were left ungraded due to a lack of evidence in the literature., Conclusions: A high level of consensus was achieved among the experts regarding the use of prophylactic gynecologic procedures. The ensuing recommendations should result in improved current practice., (Copyright © 2021. Published by Elsevier Masson SAS.)