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Molar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in the NLRP7 gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in the NLRP7, KHDC3L or PADI6 genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge.

NLRP7 is a maternal-effect gene that has a primary role in the oocyte. Its biallelic mutations are a major cause for recurrent diploid biparental hydatidiform moles (HMs). Here, we describe the full characterization of four HMs from a patient with a novel homozygous protein-truncating mutation in NLRP7. We found that some HMs have features of both complete and partial moles. Two HMs expressed p57 in the cytotrophoblast and stromal cells and exhibited divergent and discordant immunostaining. Microsatellite DNA-genotyping demonstrated that two HMs are diploid biparental and one is triploid digynic due to the failure of meiosis II. FISH analysis demonstrated triploidy in the cytotrophoblast and stromal cells in all villi. Our data highlight the atypical features of HM from patients with recessive NLRP7 mutations and the important relationship between NLRP7 defects in the oocyte and p57 expression that appear to be the main contributor to the molar phenotype regardless of the zygote genotype.

Purpose: In a low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX), the modeled hCG (human chorionic gonadotropin) residual concentration (hCGres), calculated with NONMEM program® (NM) during the first 50 treatment days, is a predictor of MTX-resistance risk. This model was implemented with another algorithm on https://www.biomarker-kinetics.org/hCG . The objective was to confirm the validity of the website estimations with respect to NM., Methods: The consistencies of modeled hCGres estimated by NM and by the website were assessed in a dataset of 60 fictive patients with simulated hCG profiles, as well as in an independent database of 531 actual patients. Moreover, the hCGres predictive values regarding MTX failure-risk were assessed., Results: The values of hCGres obtained with both methods were highly consistent in the fictive patient and in the actual patient datasets: median relative prediction errors (RPE) were - 0.059 and 9.9 × 10 -7 , respectively. The ROC AUCs for predictions of MTX failure-risk were 0.90 (95% CI 0.87,0.93) with both NM and the website. The gradual association between increasing hCGres and the 2-year MTX failure-free survival was confirmed., Conclusion: There is a high consistency of hCGres estimates obtained with the two methods. The website is meant to help clinicians in the interpretation of hCG decline curves of MTX-treated GTN patients. hCGres is now validated for more than 1690 patients in four independent datasets, and its recognition as an early predictor of MTX resistance for treatment adjustment and for the future studies should be considered.

p57 immunostaining is performed on hydropic products of conception to diagnose hydatidiform moles (HMs), which can progress to gestational trophoblastic neoplasia. Partial hydatidiform mole (PHM) and hydropic abortion (HA) display positive staining in stromal and cytotrophoblastic cells, whereas complete hydatidiform mole (CHM) is characterized by loss of p57 expression in both cell types. In some cases, an aberrant pattern is observed, called discordant p57 expression, with positive cytotrophoblast staining and negative stromal staining, or vice versa. The aim of this study was to describe the clinical, biological, and pathological characteristics of p57-discordant villi (p57DV) and other associated populations in cases of divergent p57 expression and to compare the evolutions of p57DV-associated and classic CHMs. Seventy cases of p57DV diagnosed by referent pathologists were divided into two groups, G1: p57DV ± non-CHM component (n = 22) and G2: p57DV + CHM component (n = 48). p57DV morphology was similar in the two groups. Observation of more than two populations and hybrid villi on p57 immunostaining were significantly more frequent in G2. The clinical, ultrasound, and biological presentations of p57DV-associated and classic CHMs were similar. The initial pathological diagnosis was more frequently incorrect, missing the CHM component, for the p57DV-associated CHMs. Molecular genotyping was informative in seven cases and identified as androgenetic/biparental mosaicism in four cases. These results show that p57DV are a diagnostic challenge for pathologists and that most are associated with a CHM component. However, the clinical management of p57DV-associated CHMs should be the same as that of classic CHMs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Gastric-type endocervical carcinoma is a rare entity of carcinoma of the cervix. In contrast to the intestinal type, the gastric type is not related to Human Papilloma Virus (HPV) infection and has been reported to be much more aggressive than the usual type. Oncogenic pathways involved in this poor-prognosis phenotype are largely unexplored., Methods: We compared activation of the main signaling pathways involved in cancer progression between the intestinal- (n = 5), gastric- (n = 6) and usual-type (n = 6) adenocarcinomas of the cervix using a targeted transcriptomic approach (expression of 770 genes) on FFPE samples., Results: We identified a gene-expression signature composed of 11 genes that allows the classification of these endocervical carcinoma as three distinct molecular entities. There were similarities between mucinous endocervical carcinomas (gastric and intestinal types) despite difference in pathogenesis related to HPV infection. Among HPV-related endocervical carcinoma, the intestinal type could be molecularly distinguished from the usual type by high expression of EIF2AK3 and low expression of PPFIBP2 genes, supporting its classification as a distinct entity. Overexpression of TAL1 and S1PR1 genes were characteristic of the gastric type. The usual type was characterized by high expression of occludin and VAV3 genes. Tight junction disruptions might play an essential role in the metastatic potential of mucinous endocervical carcinoma with concomitant loss of OCLN and claudin 4 proteins. An overexpression of NTRK1 transcript was observed in mucinous endocervical carcinomas when compared to the usual type., Conclusions: This transcriptomic study identified a signature that supports the classification of endocervical carcinomas as three distinct entities: usual-, intestinal- and gastric-type. It also points out to disruption of tight junctions as a potential mechanism of metastatic dissemination of these rare tumors., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aim: Gestational trophoblastic disease (GTD) is a heterogeneous group of disorders characterised by abnormal proliferation of trophoblastic tissue. Since GTD and its malignant sequel gestational trophoblastic neoplasia (GTN) are rare diseases, little evidence is available from randomised controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centres within countries. One of the goals of the 'European Organisation for Treatment of Trophoblastic Diseases' (EOTTD) is to harmonise treatment in Europe. To provide a basis for European standardisation of definitions, treatment and follow-up protocols in GTD, we composed a set of guidelines for minimal requirements and optimal management of GTD., Methods: Members from each EOTTD country attended multiple workshops during annual EOTTD meetings. Clinical guidelines were formulated by consensus and evidence where available. The following guidelines were discussed: diagnostics of GTD and GTN, treatment of low-risk GTN, high-risk GTN, ultra-high-risk GTN, placental site and epithelioid trophoblastic tumours and follow-up., Results: Between 40 and 65 EOTTD members from 17 European countries and 7 non-European countries attended the clinical workshops held on 6 occasions. Flow diagrams for patient management were composed to display minimum and best practice for most treatment situations. New agreed definitions of recurrence and chemotherapy resistance were formulated., Conclusions: Despite the many differences between and within the participating countries, an important step in uniform treatment of GTD and GTN within Europe was made by the Clinical Working Party of the EOTTD. This is an example on how guidelines and harmonisation can be achieved within international networks., Competing Interests: Conflict of interest statement None of the authors has a conflict of interest. There was no funding for this study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Our study aimed to evaluate the impact of the introduction of a new gynecologic referral service in our adult Cystic Fibrosis (CF) center on contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage., Study Design: We implemented an on-site gynecological consultation in our adult CF center in 2015. We compared the results of two surveys conducted successively in 2014 and in 2017 in a cohort of women with CF attending the Lyon CF center. Women completed the same self-report written questionnaire as in 2014. Main outcome measures were the comparisons of contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage between 2014 and 2017., Results: All the 136 women (100%) who attended the clinic in 2017 participated. Contraceptive prevalence rate increased from 69%(CI95%:60.3-78.1) to 86%(CI95%:79.6-92.9) between 2014 and 2017 (p = 0.005). Among transplanted patients, the contraceptive prevalence rate was 92.3%(CI95%:82.0-100) in 2017. Long acting reversible contraceptive use markedly increased from 10% to 21.6% (p = 0.005). The proportion of women that reported an access to gynecological care increased between 2014 and 2017 (74%(CI95%:66.3-82.0) vs 91%(CI95%:86.9-95.4), p < 0.005) and reached 100% among transplanted patients. Cervical cancer screening improved (55%(CI95%:51.2-68.8) vs 85%(CI95%:78.6-90.6) women ever screened) (p < 0.0005) and reached 100% among transplanted patients., Conclusions: We observed an improvement in contraceptive coverage and gynecological care of adult women with CF following the implementation of a dedicated gynecological consultation in the CF center., Implications: Service linkages and formal links between CF centers and gynecologists can facilitate access to disease-specific contraceptive counseling, adequate gynecological management and cervical cancer screening., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although epithelial-to-mesenchymal transition (EMT) has been described in the development of complete hydatidiform moles and the invasion of the maternal decidua by trophoblasts during normal human placentation, its implication in gestational trophoblastic neoplasm (GTN) without villi is totally unknown. We studied the immunoexpression of EMT transcription factors (TWIST1, ZEB1, ZEB2), E-cadherin, and vimentin in 18 trophoblastic tumors and pseudo-tumors. Weak nuclear TWIST1 immunostaining was seen in 5% to 10% of all trophoblastic cells, without ZEB1 and ZEB2 nuclear staining. Trophoblastic cells did not express vimentin, and the expression of E-cadherin was maintained in all cases, indicating the absence of EMT features in GTN.

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Few studies in the literature take into account the WHO's 2014 redefinition of the characteristics of mucinous adenocarcinoma of the uterine cervix. Our objective was to describe the characteristics of a group of these patients., Material and Methods: This was a retrospective descriptive study of patients diagnosed between 1 January 2005 and 31 May 2016 in three hospitals in Lyon, France. All the cases of cervical adenocarcinoma were reanalysed by an expert in gynaecological pathology to retain the mucinous subtypes as defined in the 2014 WHO classification. We analysed their clinical and pathological characteristics., Results: Among the 82 cases of cervical adenocarcinoma, 21 (26%) were diagnosed as mucinous. Ten were gastric type, of which four were in the extremely well differentiated form of minimal deviation adenocarcinomas, six were intestinal type, two were signet-ring cell type, and three were not otherwise specified. The patients' mean age was 42 years and 18 patients were premenopausal. The revealing symptom was metrorrhagia in eight cases (38%) and mucinous vaginal discharge in four (19%). Fifteen (72%) of the cervical smear were abnormal. Five (31%) of the 16 patients with gastric or intestinal type adenocarcinoma had a specific radiological presentation: multiple cysts of the uterine isthmus, visible on ultrasound and with T2 hyperintensity on MRI., Conclusion: Mucinous adenocarcinoma is a rare form of cervical cancer that can be confused with other pathological types. It can be detected using cervical smears and should be suspected in cases of mucinous discharge and characteristic MRI features., (Copyright © 2019. Published by Elsevier Masson SAS.)

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). In case of ovarian, Fallopian tube or primitive peritoneal cancer of FIGO III-IV stages, thoraco-abdomino-pelvic CT scan with injection (grade B) is recommended. Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A)., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Cancer of the uterine cervix is the fourth most common cancer in women worldwide, and the fourth leading cause of cancer death in women. Squamous cell carcinoma is the first type of cervical cancer (about 75% of cases), and adenocarcinoma the second. Adenocarcinoma of the uterine cervix were redefined in the 2014 WHO classification. Endocervical adenocarcinoma, usual type, is the mose common. Mucinous adenocarcinoma were classified by this classification into different subtypes: gatric type, intestinal type and signet-ring cell type. This literature review shows the caracteristics of these various subtypes of cervical cancer, little known. These are physiopathological, clinical, cytological histological, pronostic caracteristics, and their treatments., (Copyright © 2019. Published by Elsevier Masson SAS.)

Objectives: To describe MRI features of accessory cavitated uterine mass (ACUM) with surgical correlations., Methods: Eleven young women with an ACUM at pathology underwent preoperative pelvic MRI. Two experienced radiologists retrospectively analysed MR images in consensus to determine the lesion location within the uterus, its size, morphology (shape and boundaries), and structure reporting the signal and enhancement of its different parts compared to myometrium. The presence of an associated urogenital malformation or other gynaecological anomaly was reported. MRI features were correlated with surgical findings., Results: All 11 lesions were well correlated with surgical findings, lateralised (seven were left-sided), and located under the horn and the round ligament insertion. Nine were located within the external myometrium, bulging into the broad ligament. Two were extrauterine, entirely located within the broad ligament. On MRI, the mean size was 28 mm (range 17-60 mm). Nine lesions were round-shaped, two were oval; all had regular boundaries. At surgery, the ACUM were not encapsulated but were possible to enucleate. On MRI, all lesions were well defined and showed a central haemorrhagic cavity surrounded by a regular ring (mean thickness, 5 mm) which had the same signal compared to the junctional zone. ACUM was isolated in all women, without urogenital malformation, adenomyosis or deep endometriosis., Conclusions: On MRI, ACUM was an isolated round accessory cavitated functional non-communicating horn-like aspect in an otherwise normal uterus. MRI may facilitate timely diagnosis and appropriate curative fertility-sparing laparoscopic resection., Key Points: • ACUM is rare, with delayed diagnosis in young women with severe dysmenorrhoea. Pelvic MRI facilitates timely diagnosis and appropriate curative fertility-sparing laparoscopic resection. • Quasi-systematically located under the uterine round ligament insertion, ACUM may be intramyometrial and/or in the broad ligament. • On MRI ACUM resemble a non-communicating functional accessory horn within a normal uterus; the mass, most often round-shaped, had a central haemorrhagic cavity surrounded by a regular ring which had the same low signal compared to the uterine junctional zone.

Objective: Epithelioid Trophoblastic Tumor (ETT) is an extremely rare form of Gestational Trophoblastic Neoplasia (GTN). Knowledge on prognostic factors and optimal management is limited. We identified prognostic factors, optimal treatment, and outcome from the world's largest case series of patients with ETT., Methods: Patients were selected from the international Placental Site Trophoblastic Tumor (PSTT) and ETT database. Fifty-four patients diagnosed with ETT or mixed PSTT/ETT between 2001 and 2016 were included. Cox regression analysis was used to identify prognostic factors for overall survival (OS)., Results: Forty-five patients with ETT and 9 patients with PSTT/ETT were included. Thirty-six patients had FIGO stage I and 18 had stages II-IV disease. Patients were treated with surgery (n = 23), chemotherapy (n = 6), or a combination of surgery and chemotherapy (n = 25). In total, 39 patients survived, including 22 patients with complete sustained hCG remission for at least 1 year. Patients treated with surgery as first line treatment had early-stage disease and all survived. Most patients treated with chemotherapy with or without surgery had FIGO stages II-IV disease (55%). They underwent multiple lines of chemotherapy. Eleven of them did not survive. Interval since antecedent pregnancy and FIGO stage were prognostic factors of OS (p = 0.012; p = 0.023 respectively)., Conclusions: Advanced-stage disease and an interval of ≥48 months since the antecedent pregnancy are poor prognostic factors of ETT. Surgery seems adequate for early-stage disease with a shorter interval. Advanced-stage disease requires a combination of treatment modalities. Because of its rarity, ETT should be treated in a centre with experience in GTN., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B)., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the survival and functional outcome of patients with brain metastasis due to gestational trophoblastic neoplasia (GTN)., Methods: A 17-year retrospective study based on case review of women with brain metastasis from GTN identified by the electronic databases held in the French Reference Centre., Primary Outcome Measure: 5-year overall survival calculated with the Kaplan-Meier method., Secondary Outcome Measures: causes of death, prognostic factors and functional outcomes., Results: 21 patients had GTN brain metastasis and were treated with multidrug chemotherapy without concomitant whole-brain radiation therapy. Three patients died early (< 4 weeks) of cerebral hemorrhage, 3 died ≥ 1 months after treatment initiation and 15 were alive at the date of last contact. The overall survival rate at 5 years was 69.8% (95% CI 44.3-85.3). After excluding early deaths, the survival rate at 5 years was 81.5% (95% CI 52.3-93.7). No predictive factor of survival was identified. Although 11 of the 12 (92%) surviving patients contacted still reported sequelae, nine of them (75%) had resumed a normal life., Conclusions: After excluding early deaths, this study implies a high survival rate in patients with brain metastasis from GTN. These results were achieved in the total absence of whole-brain radiotherapy and almost completely without the need for intrathecal methotrexate.

Early stage ovarian epithelial cancer (stage I according to the FIGO classification, i.e. limited to ovaries) affects 20% to 33% of patients with ovarian cancer. This chapter only describes data on these presumed early stages. The rate of occult epiploic metastases varies from 2% to 4%, and leads to over-staging in stage III A of 3% to 11% of patients. Performing an omentectomy does not result in a change in survival in this situation (NP4). The rate of appendix metastasis ranges from 0% to 26.7% (NP4). In the mucinous subtype, this rate can reach 53% if the appendix is macroscopically abnormal (NP2). The rate of positive peritoneal cytology ranges from 20.9% to 27%. Positive peritoneal cytology is responsible for over-staging of patients in 4.3% to 52% of cases and appears as a poor prognostic factor on survival (NP4). The rate of occult peritoneal metastases varies from 1.1% to 16%. Performing these peritoneal biopsies results in over-staging of 4% to 7.1% (NP4). In the management of ovarian cancers at a presumed early stage, it is recommended to perform: omentectomy, peritoneal biopsies, cytology, appendectomy (grade C). In case of incomplete or incomplete initial staging, restaging including omentectomy, peritoneal biopsies and appendectomy (if not explored) is recommended; especially in the absence of a reported indication of chemotherapy. The lymph node invasion rate ranges from 6.3% to 22%. It is 4.5% to 18% for stages I and 17.5% to 31% in stages II. Between 8.5% and 13% of patients with suspected early stage ovarian cancer are reclassified to stage IIIA1 following the completion of lymphadenectomy (NP3). Pelvic and lumbo-aortic lymphadenectomy improves the survival of patients with ovarian cancer at a presumptive early stage (NP2). Pelvic and lumbo-aortic lymphadenectomy is recommended for presumed early ovarian stages (grade B). In case of initial treatment of early-stage ovarian cancer without lymph node staging, restadification including lymphadenectomy is recommended; especially in the absence of a stated indication of chemotherapy (grade B). No studies have shown any laparoscopic disadvantage compared to laparotomy for feasibility, safety, or postoperative rehabilitation (NP3) in surgical staging of patients with early-stage ovarian cancer. For the initial surgical management of these patients, the choice between laparoscopy or laparotomy depends on local conditions (tumor size) and surgical expertise. If complete surgery without risk of tumor rupture is possible, the laparoscopic approach is preferred (grade C). In the opposite case, median laparotomy is recommended. As part of surgical restadification, the laparoscopic approach is recommended (grade C). Intraoperative tumor rupture leads to a decrease in disease free survival (hazard ratio=2.28) and overall survival (hazard ratio=3.79) (NP2). It is recommended that all precautions be taken to avoid perioperative ovarian tumor rupture, including the intraoperative decision of laparoconversion (grade C). There is no specific study to answer the question of the feasibility of a one-time or two-time surgery during an extemporane diagnosis of an early stage ovarian cancer. The high sensitivity and specificity of this extemporane examination in this situation makes it possible to consider a surgical management of staging during the same operating time., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in gestational trophoblastic disease, we evaluated differences and similarities between protocols in EOTTD countries., Methods: Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of gestational trophoblastic disease and gestational trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up., Results: Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar gestational trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk gestational trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar gestational trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements., Conclusions: This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several gestationaltrophoblastic disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Diagnosis and treatment of endometriosis may be complex and therefore justify the discussion of therapeutic decisions in a multidisciplinary endometriosis board (MEB). The development of endometriosis regional expert centers requires an assessment of the quality and relevance of MEB., Methods: Qualitiative retrospective study on patients whose management was discussed in Centre Hospitalier Lyon-Sud between June 2013 and December 2017., Results: Among 376 patients presented in MEB, 309 (80.2%) were painful and 184 (59.5%) had complex endometriosis. A complete clinical evaluation was performed in 120 (38.8%) patients. MRI was performed for 370 (98.4%) patients including 303 (81.9%) with a second reading by an expert radiologist. These second readings allowed a diagnosis correction in 88 (60.7 %) patients with complex endometriosis. MR enterography (27.8 %) and rectal endoscopic sonography (14.4%) were the most frequently used third-line exams to complete the initial imaging of digestive lesion in patients with rectal endometriosis. Surgery was proposed for 199 (52,9%) patients including 108 (58,7%) with complex endometriosis., Conclusion: One of the major interests of MEB in endometriosis is the second reading of MRI, which, by identifying complex endometriosis initially undiagnosed or underestimated, enabled to better discuss the benefits/risks of therapeutic choices, and to organize complex surgeries when those were retained. The development of MEB in regional expert centers will contribute to optimizing the relevance of care for patients with endometriosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: This study aimed to assess the outcome of first-line hysterectomy in patients diagnosed as having gestational trophoblastic neoplasia (GTN) whose postoperative imaging showed lung images considered as metastases., Methods: From 1999 to 2016, patients no longer wishing to conceive, treated by their initial physician by hysterectomy, and whose postoperative imaging workup showed lung images considered as metastasis were identified in the French Trophoblastic Disease Reference Center database. We sought to identify significant predictive factors of requiring salvage chemotherapy., Results: Thirty patients were identified with a maximum number of 2 visible lung nodules and a median largest size of 14 mm on chest x-ray. Nine of these patients had an International Federation of Gynecology and Obstetrics score of higher than 6, and there were no postterm GTN. Twenty-two patients (73.33%; 95% confidence interval, 54.11-87.72; P = 0.0053) normalized their human chorionic gonadotropin (hCG) without salvage chemotherapy, whereas 7 received 1 line of salvage monochemotherapy (8-day methotrexate) and 1 required 2 lines of monochemotherapy (5-day actinomycin D after failure of methotrexate). After a 12.45-month median follow-up (range, 3-48.4 months) since the first normalized hCG, none of these patients died. The median interval between successful hysterectomy and hCG normalization was 3.15 months (range, 1.6-8.7 months). Patients who required salvage chemotherapy had a median size of the largest lung metastasis on chest computed tomography of 4 mm larger than those cured by hysterectomy (P = 0.0455)., Conclusions: For GTN patients no longer wishing to conceive with lung metastases discovered postoperatively, treated by hysterectomy, and whose hCG is decreasing, it is reasonable to expect and to inform patients that approximately 27% will require salvage chemotherapy. However, in patients with lung metastases discovered preoperatively, evidence to recommend first-line hysterectomy is insufficient and these patients should receive first-line chemotherapy.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors., (© 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

First-line diagnostic investigations for endometriosis are physical examination and pelvic ultrasound. The second-line investigations are: targeted pelvic examination performed by an expert clinician, transvaginal ultrasound performed by an expert physician sonographer (radiologist or gynaecologist), and pelvic MRI. Management of endometriosis is recommended when the disease has a functional impact. Recommended first-line hormonal therapies for the management of endometriosis-related pain are combined hormonal contraceptives (CHCs) or the 52mg levonorgestrel-releasing intrauterine system (IUS). There is no evidence base on which to recommend systematic preoperative hormonal therapy solely to prevent surgical complications or facilitate surgery. After surgery for endometriosis, a CHC or 52mg levonorgestrel-releasing IUS is recommended as first-line treatment when pregnancy is not desired. In the event of failure of the initial treatment, recurrence, or multiorgan involvement, a multidisciplinary team meeting is recommended, involving physicians, surgeons and other professionals. A laparoscopic approach is recommended for surgical treatment of endometriosis. HRT can be offered to postmenopausal women who have undergone surgical treatment for endometriosis. Antigonadotrophic hormonal therapy is not recommended for patients with endometriosis and infertility to increase the chances of spontaneous pregnancy, including postoperatively. Fertility preservation options must be discussed with patients undergoing surgery for ovarian endometriomas., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Human papillomavirus type 16 (HPV16) and other oncoviruses have been shown to block innate immune responses and to persist in the host. However, to avoid viral persistence, the immune response attempts to clear the infection. IL-1β is a powerful cytokine produced when viral motifs are sensed by innate receptors that are members of the inflammasome family. Whether oncoviruses such as HPV16 can activate the inflammasome pathway remains unknown. Here, we show that infection of human keratinocytes with HPV16 induced the secretion of IL-1β. Yet, upon expression of the viral early genes, IL-1β transcription was blocked. We went on to show that expression of the viral oncoprotein E6 in human keratinocytes inhibited IRF6 transcription which we revealed regulated IL-1β promoter activity. Preventing E6 expression using siRNA, or using E6 mutants that prevented degradation of p53, showed that p53 regulated IRF6 transcription. HPV16 abrogation of p53 binding to the IRF6 promoter was shown by ChIP in tissues from patients with cervical cancer. Thus E6 inhibition of IRF6 is an escape strategy used by HPV16 to block the production IL-1β. Our findings reveal a struggle between oncoviral persistence and host immunity; which is centered on IL-1β regulation., Competing Interests: The authors have declared that no competing interests exist.

Background: Low-risk gestational trophoblastic neoplasia (GTN) patients (FIGO score ≤6) are generally treated with single agent chemotherapy (methotrexate or dactinomycin) resulting in a 5-year mortality rate of 0.3%. However, despite these encouraging survival rates, chemotherapy is associated with significant adverse events in most patients. Although it is generally accepted that patients who no longer wish to conceive may be treated by hysterectomy for a hydatidiform mole, the evidence to support this strategy in low-risk GTN patients is lacking., Objectives: To describe the survival, efficacy, and tolerance associated with first-line hysterectomy in low-risk non-metastatic GTN patients., Study Design: Seventy-four of 1072 low-risk GTN patients treated in the French Center underwent first-line hysterectomy. Patients data with successful first-line hysterectomy were retrospectively compared to those requiring further salvage chemotherapy., Results: First-line hysterectomy was followed by hCG normalization in 61 patients (82.4%, 95% confidence interval [CI] 71.8-90.3) without any further salvage chemotherapy, whereas 13 patients required salvage chemotherapy. After multivariate analysis, a FIGO score of 5-6 (exact OR 8.961, 95%CI 1.60-64.96), and the presence of choriocarcinoma (exact OR 14.295, 95%CI 1.78-138.13) were associated with the risk of requiring salvage chemotherapy., Conclusion: Hysterectomy as a first-line treatment is effective without salvage chemotherapy in 82.4% of women with low-risk non-metastatic GTN and can be presented as an alternative to single-agent chemotherapy when childbearing considerations have been fulfilled. In young patients, this therapeutic option should not be considered because single-agent chemotherapies are curative in nearly 100% of patients while maintaining fertility., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Menstrual toxic shock syndrome (mTSS) is a severe disease that occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock toxin 1 and who use tampons. The aim of the present study was to determine the impact of the composition of vaginal microbial communities on tampon colonisation by S. aureus during menses. We analysed the microbiota in menstrual fluids extracted from tampons from 108 healthy women and 7 mTSS cases. Using culture, S. aureus was detected in menstrual fluids of 40% of healthy volunteers and 100% of mTSS patients. Between class analysis of culturomic and 16S rRNA gene metabarcoding data indicated that the composition of the tampons' microbiota differs according to the presence or absence of S. aureus and identify discriminating genera. However, the bacterial communities of tampon fluid positive for S. aureus did not cluster together. No difference in tampon microbiome richness, diversity, and ecological distance was observed between tampon vaginal fluids with or without S. aureus, and between healthy donors carrying S. aureus and mTSS patients. Our results show that the vagina is a major niche of. S. aureus in tampon users and the composition of the tampon microbiota control its virulence though more complex interactions than simple inhibition by lactic acid-producing bacterial species.

Objective: The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate., Methods: From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure., Results: A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3-83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post-dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98-50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%)., Conclusion: Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies.

Endometriosis is a common condition that causes pain and infertility. It can lead to absenteeism and also to multiple surgeries with a consequent risk of impaired fertility, and constitutes a major public health cost. Despite the existence of numerous national and international guidelines, the management of endometriosis remains suboptimal. To address this issue, the French College of Gynaecologists and Obstetricians (CNGOF) and the Society of Gynaecological and Pelvic Surgery (SCGP) convened a committee of experts tasked with defining the criteria for establishing a system of care networks, headed by Expert Centres, covering all of mainland France and its overseas territories. This document sets out the criteria for the designation of Expert Centres. It will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with endometriosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Contamination of groundwater resources by an immiscible organic phase commonly called NAPL (Non Aqueous Phase Liquid) represents a major scientific challenge considering the residence time of such a pollutant. This contamination leads to the formation of NAPL blobs trapped in the soil and impact of this residual saturation cannot be ignored for correct predictions of the contaminant fate. In this paper, we present results of micromodel experiments on the dissolution of pure hydrocarbon phase (toluene). They were conducted for two values of the Péclet number. These experiments provide data for comparison and validation of a two-phase non-equilibrium theoretical model developed by Quintard and Whitaker (1994) using the volume averaging method. The model was directly upscaled from the averaged pore-scale mass balance equations. The effective properties of the macroscopic model were calculated over periodic unit cells designed from images of the experimental flow cell. Comparison of experimental and numerical results shows that the transport model predicts correctly - with no fitting parameters - the main mechanisms of NAPL mass transfer. The study highlights the crucial need of having a fair recovery of pore-scale characteristic lengths to predict the mass transfer coefficient with accuracy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

First-line investigations to diagnose endometriosis are clinical examination and pelvic ultrasound. Second-line investigations include pelvic examination performed by a referent clinician, transvaginal ultrasound performed by a referent echographist, and pelvic MRI. It is recommended to treat endometriosis when it is symptomatic. First-line hormonal treatments recommended for the management of painful endometriosis are combined with hormonal contraceptives or levonorgestrel 52mg IUD. There is no evidence to recommend systematic preoperative hormonal therapy for the unique purpose of preventing the risk of surgical complications or facilitating surgery. After endometriosis surgery, combined hormonal contraceptives or levonorgestrel SIU 52mg are recommended as first-line therapy in the absence of desire of pregnancy. In case of initial treatment failure, recurrence, or multiple organ involvement by endometriosis, medico-surgical and multidisciplinary discussion is recommended. The laparoscopic approach is recommended for the surgical treatment of endometriosis. HRT may be offered in postmenopausal women operated for endometriosis. In case of infertility related to endometriosis, it is not recommended to prescribe anti-gonadotropic hormone therapy to increase the rate of spontaneous pregnancy, including postoperatively. The possibilities of fertility preservation should be discussed with the patient in case of surgery for ovarian endometrioma., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Urinary tract involvement by endometriosis is reported in 1% of endometriosis patients (NP3). Consequences range from pelvic pain for bladder localizations to silent kidney loss in case of chronic ureteral obstruction (NP3). The feasibility of laparoscopic management was widely proven (NP3) and may reduce hospital stay length (NP4). Radical surgery with partial cystectomy for bladder localizations was shown to significantly and durably reduce pain symptoms with low risk of a severe postoperative complications (NP3). Medical hormonal treatment also shows short-term reduction of pain symptoms (NP4). Transureteral resection of bladder endometriosis nodule is not recommended (grade C) because of a high postoperative recurrence rate (NP4). Given a high risk of silent kidney loss, it is recommended that patients with ureteral involvement by endometriosis are managed by a multidisciplinary team considering urinary and potential extra-urinary localizations of endometriosis (grade C). No recommendation can be made on which technique to prefer between conservative (ureterolysis) or radical surgical techniques or on benefit and length of ureteral stents in case of ureteral involvement. Surgical management of bladder and ureteral localizations of endometriosis do not seem to be associated with altered or improved postoperative fertility (NP4). Since late postoperative ureteral anastomosis stenosis were reported with silent kidney loss, repeated postoperative imaging monitoring is justified (expert opinion)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: The Collège national des gynécologues obstétriciens français (CNGOF), in agreement with the Société de chirurgie gynécologique et pelvienne (SCGP), has set up a commission in 2017 to define endometriosis expert centres, with the aim of optimizing endometriosis care in France., Methods: The committee included members from university and general hospitals as well as private facilities, representing medical, surgical and radiological aspects of endometriosis care. Opinion of endometriosis patients' associations was obtained prior to writing this work. The final text was presented and unanimously validated by the members of the CNGOF Board of Directors at its meeting of October 13, 2017., Results: Based on analysis of current management of endometriosis and the last ten years opportunities in France, the committee has been able to define the contours of endometriosis expert centres. The objectives, production specifications, mode of operation, missions and funding for these centres were described. The following missions have been specifically defined: territorial organization, global and referral care, communication and teaching as well as research and evaluation., Conclusion: Because of its daily impact for women and its economic burden in France, endometriosis justifies launching of expert centres throughout the country with formal accreditation by health authorities, ideally as part of the National Health Plan., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: Insufficient gynecological follow-up and cervical screening has been reported in women with cystic fibrosis (CF). Some of these patients will require a pulmonary transplantation, known to be associated with a higher risk of cervical dysplasia. The aim of this study was to explore the results of cervical screening in adult women with CF, and to report the prevalence of abnormal pap smear tests in this population., Study Design: We retrospectively analyzed medical records of sexually active women with CF who attended a gynecological consultation in Lyon University CF referral center between June 2014 and December 2015. The primary outcome was the result of the pap smear test., Results: Forty-seven women (32 non-transplanted and 15 transplanted) were included in the study. The median age of the patients was 28 (range 18-53). The clinical examination revealed that 20 (42.5%) women presented an abnormality (inflammatory cervix, cervical or vulvovaginal condyloma). An abnormal pap smear was found in 8/32 (25%) non transplanted women and in 5/15 (33.3%) transplanted women, with no significant difference between the two groups (p=0.75): seven atypical squamous cells of undetermined significance (ASC-US), five low grade squamous intraepithelial lesion (LSIL), one atypical glandular cells (AGC). Six (12.8%) (four non transplanted, and two transplanted) women had an histologically proven dysplasia (four Cervical Intraepithelial Neoplasia (CIN)1, one CIN2, and one endocervical adenocarcinoma in situ). Overall, ten (21.3%) women had a Human Papilloma Virus (HPV) related disease (cervical and/or vulvovaginal)., Conclusion: A high proportion of transplanted and non-transplanted women with CF had abnormal pap smear tests and cervical dysplasia. A regular gynaecological follow-up, periodic cervical screening, and routine HPV vaccination are strongly recommended in this population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Choriocarcinoma is a highly malignant neoplasm resulting from the malignant transformation of proliferating trophoblastic cells and the molecular mechanisms leading to this transformation remain to be characterized. We report here the first case of a female germline TP53 mutation carrier who developed, as a first tumour, a lung choriocarcinoma, 6 months after a normal delivery. Molecular analyses established the gestational origin of the choriocarcinoma and showed, within the tumour, the presence of the germline mutant TP53 allele and loss of the wild-type allele. Resistance to methotrexate chemotherapy led to perform a surgical resection of the tumour. In agreement with the permissive role of TP53 mutations to oncogenic events, this report strongly suggests that TP53 mutations may promote malignant transformation of proliferating trophoblastic cells. Therefore, female TP53 mutation carriers may have an increased risk of developing gestational choriocarcinoma and might benefit from β-hCG level monitoring after pregnancy.

Aim: To investigate the prognostic value of modeled CA-125 kinetic parameters regarding surgery outcomes and time to second-line chemotherapy in a population of ovarian cancer patients treated with neoadjuvant chemotherapy followed by interval cytoreduction., Patients and Methods: This retrospective study included consecutive patients with FIGO stage IIIc/IV ovarian cancer treated between 2006 and 2014. We characterized CA-125 kinetics and identified modeled kinetic parameters., Results: Fifty four patients were included. KELIM (modeled CA-125 elimination rate constant) was an independent predictive parameter of optimal cytoreduction (OR=0.18; 95% CI=0.04-0.69; p=0.02). In the optimal cytoreduction population (40 patients, 74.1%), E 50 (concentration producing 50% of the maximum chemotherapy effect) was a significant prognostic parameter regarding time to second-line chemotherapy (HR=0.38; 95% CI=0.173-0.854; p=0.019)., Conclusion: We identified CA-125 modeled kinetic parameters during neoadjuvant chemotherapy harboring potential predictive values regarding the likelihood of optimal cytoreduction, along with time to second-line chemotherapy in optimally-cytoreduced patients., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endometriosis is a frequent pathology with a high incidence of deep infiltrating endometriosis and complex forms that can affect 20% of patients with endometriosis. The incidence of infertility associated with endometriosis can reach 50%. The complexity of care requires the creation of expert centers working in networks with general practitioners. Criteria for defining these expert centers are being drawn up, based on structural criteria (multidisciplinary consultation meeting), links with medical assistance structures for procreation and activity criteria for severe and complex forms (number of interventions per center and per surgeon)., (Copyright © 2017. Published by Elsevier Masson SAS.)

Objective: To develop a consensus of experts on the use of local estrogens in female urinary incontinence., Material and Method: Following a formalized consensus method (DELPHI), a questionnaire was produced and sent to a first round and then to a second round of experts. The questionnaire consisted of proposals for recommendations for the use of local estrogens in the context of female urinary incontinence. The Survey Monkey ® survey software allowed the questionnaire to be distributed and the answers obtained to be analyzed., Results: Eight experts responded to the first round questionnaire. Seven formulations were deleted, 3 amended and 4 added to the first round questionnaire following expert advice. Twenty-six experts replied to the second round questionnaire, 24 of which were complete. Ten of the 21 proposals were approved at more than 80%, including five with strong agreement regarding the recognized benefit of local estrogens in urinary incontinence due to overactive bladder, the absence of data from the literature to demonstrate over-risk of hormone-dependent cancer under local estrogens and the need for follow-up of patients under this treatment. Six proposals were not the subject of a consensus and concerned the prescription modalities (maximum duration, effective minimum dose, prescription before surgery for incontinence)., Conclusion: Although local estrogens did not have regulatory approval in urinary incontinence, more than 80% of these experts recognized their benefit in the management of urinary incontinence in women with vulvo-vaginal atrophy, particularly in the case of urinary urge incontinence., Level of Proof: 4., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Given the unique intra-peritoneal anatomic location of the adnexa, tubo-ovarian diseases can commonly spread into the peritoneal cavity. Peritoneal seeding may occur in a spectrum of adnexal conditions including infectious diseases, endometriosis, and benign or malignant primary or secondary ovarian tumors. CT is usually the imaging modality on which the concomitant involvement of the peritoneum and the ovary is depicted. The first diagnosis to be considered by the radiologist is generally peritoneal carcinomatosis from ovarian cancer but other conditions cited above have also to be borne in mind and may be suggested on the basis of careful assessment of CT findings or on further MR findings. MRI may indeed help characterize the lesions in some cases. The purpose of this review is to describe the clinical and imaging patterns of peritoneal involvement that may be found in association with different ovarian lesions. Familiarity with these patterns and diagnoses will help the radiologist narrow the differential diagnosis and make an accurate diagnosis, thus facilitating patient management and avoiding unnecessary invasive treatment.

Objective: The aim of this study was to evaluate 36 quality indicators (QIs) for monitoring the quality of care of uterine cancer to be implemented in the EFFECT (effectiveness of endometrial cancer treatment) project., Methods: The 36 QIs were evaluated in the first 10 patients diagnosed with endometrial cancer and managed in 14 French hospitals in 2011. To assess the status of each QI, a questionnaire detailing the 36 QIs was sent to each hospital, and the information was cross-checked with information from the multidisciplinary staff meeting, surgical reports, and pathological reports. The QIs were evaluated in terms of measurability and improvability. The remaining QIs were evaluated with a multiple correspondence analysis to highlight the interrelationships between qualitative variables describing a population., Results: Thirteen of the 14 institutions responded to the survey for a total of 130 patients. Twenty-five of the 36 QIs affected less than 80% of the patients. Thirteen QIs were found not to be improvable because they reached more than 95% of the theoretical target. Finally, 5 QIs concerning more than 80% of the patients were found to be improvable. The multiple correspondence analysis finally identified 3 dimensions-outcome, safety, and perioperative management-that included the 5 QIs., Conclusions: In the present study, 5 of the 36 QIs suggested by the EFFECT project seem to be sufficient to report on the quality of endometrial cancer management. Further studies are needed to correlate the information provided by those 5 questions and the relevant outcomes reflecting quality of care in endometrial cancer.

Objective: To assess postoperative complications, improvement of pain symptoms and residual urinary functional symptoms after surgery for deep infiltrative endometriosis affecting ureter or bladder., Methods: Retrospective study of complications (Clavien-Dindo classification), pain (visual analog scale [VAS]) and urinary functional symptoms (Urinary Symptom Profile questionnaire [USP]) of patients surgically treated between 2007 and 2015 in University Hospitals of Lyon., Results: Among 31 patients with endometriosis involving the bladder, 83.9% had a partial cystectomy and 16.1% an extra-mucosal resection. Among patients (n=20) with ureteral involvement, 85% had ureterectomy with ureterocystoneostomy and 15% had only ureterolysis. Grade III postoperative complications occurred in 6% and 0% of patients with bladder or ureteral surgery, respectively and no grade IV or V complications were reported. Mean bladder VAS dropped from 5.3±4.2 to 0.3±0.9 after a follow-up of 42 months (P<0.0001). In patients with ureteral involvement, mean flank VAS dropped from 3.6 to 0.9 after a follow-up of 33 months (P<0.0005). Mean postoperative USP score for dysuria and detrusor overactivity were 1.35/9 and 2.48/21 in case of bladder involvement, and 1.10/9 and 2.15/21 in case of ureteral involvement., Conclusion: Multidisciplinary surgical management of deep infiltrative endometriosis affecting urinary tract was associated to a low risk of severe postoperative complications and to a long-term significant improvement of pain symptoms without significant residual functional urinary symptoms., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes., Methods: We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylin-eosin-safran-stained slides., Results: PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles, ATS scores were maximal at 8 in 100%, 100%, and 75% of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity., Conclusions: We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti-PD-L1 drug in GTD patients has been activated.

Study Objective: To assess the anatomic efficacy and safety of synthetic glue to fix prosthetic material in laparoscopic sacrocolpopexy., Design: A 1-year follow-up in a prospective multicenter pilot study between November 2013 and November 2014 (Canadian Task Force Classification II-2)., Setting: An academic urogynecology research hospital., Patients: Seventy consecutive patients with Pelvic Organ Prolapse Quantification stage ≥3 anterior and/or medial prolapse underwent laparoscopic sacrocolpopexy., Interventions: All women underwent laparoscopic sacrocolpopexy with the same standardized technique using a synthetic surgical glue to fix anterior and posterior meshes., Measurements and Main Results: Patients were followed up at 1 month and 1 year, with anatomic and functional assessment (Pelvic Floor Distress Inventory-20, Pelvic Floor Impact Questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12). Anatomic success was defined as 1-year Pelvic Organ Prolapse Quantification stage ≤1. Sixty-six patients were included; the mean age was 56.7 ± 1.2 years. The mean operative time was 145 ± 5 minutes. The mean glue fixation time was less than 2 minutes for both anterior and posterior meshes. The 1-year anatomic success rate was 87.5% in the anterior compartment (Ba at -2.3 cm, p < .0001) and 95.3% in the medial compartment (point C at -6.1 cm, p < .0001). There were no intra- or postoperative complications and no cases of mesh exposure; 5 cases of mesh shrinkage (7.8%) were observed at 1 year. The postoperative urinary stress incontinence rate was 29.7% at 1 year. Eight patients (12.1%) underwent revision surgery with transobturator tape. All quality of life scores showed significant improvement (p < .0001) at 1 year., Conclusion: Synthetic glue attachment of prosthetic material in laparoscopic sacrocolpopexy proved straightforward, safe, time-saving, and effective at 1 year. Prospective randomized studies will be needed to confirm the long-term benefit., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis., Materials and Methods: Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by κ statistics., Results: Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right-sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes., Conclusion: MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement., Key Points: • MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. • Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1-weighted sequences. • Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. • MRI can help in timely diagnosis of diaphragmatic endometriosis.

Tumors of trophoblast implantation site TTSI are rare gestational tumors. This case highlights the diagnostic difficulties and treatment of tumors of trophoblastic implantation site early. Patient of 28 years with no medical history, G1P1 who gave birth 11 months ago presented bleeding with an HCG level of 73IU that led to the diagnosis of early miscarriage. Treatment of miscarriage by hysteroscopy and curettage is complicated leading to the realization of an abdominopelvic CT and pelvic ultrasound that show an atypical uterine vascularity and an intracavitary heterogeneous mass. The pelvic MRI performed evokes a TTSI stage I. A hysterectomy with bilateral salpingectomy and ovarian conservation is achieved. Despite the standard treatment with surgery the HCG levels do not normalize before seven months after surgery. This indicates an adjuvant chemotherapy, the patient refuses. The presented case illustrates the diagnostic difficulties of the disease. He noted the importance of the second reading network proposed by the specialized center in Lyon. It also raises the question of adjuvant chemotherapy in some cases of early stage TTSI. The challenge is to define cases requiring adjuvant therapy. Predictors of chemotherapy in early stages could be tumor size, degree of infiltration of the myometrium and mutation p53. Amenorrhea, bleeding associated with uterine atypical vascularization, and atypical development of HCG<1000IU and/or unusual complications of treatment of miscarriage should evoke a tumor site trophoblastic implantation. Hysterectomy is the first treatment in early stages. Tumor size, degree of infiltration of the myometrium and mutation p53 are predictors to assess in multicentre studies to define the indications of postoperative chemotherapy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: HELLP syndrome is a combination of symptoms described as hemolysis, elevated liver enzymes and low platelets, that complicates 0.01-0.6 % of pregnancies. HELLP syndrome has been scarcely reported associated with partial moles, another rare complication of pregnancy. This manuscript describes the only reported case of HELLP syndrome associated with a complete invasive hydatiform mole., Case Presentation: We report a perimenopausal patient in prolonged remission from an uncommon high-risk invasive complete mole. The diagnosis was set in a context of early onset preeclampsia and HELLP syndrome. The development of life-threatening complications required primary hysterectomy. Postoperative hCG quickly returned to normal with EMA/CO multi-agent chemotherapy., Conclusion: Our patient is in prolonged remission from a complete mole complicated with EOP and HELLP syndrome. This exceptional case of complicated gestational trophoblastic neoplasia reflects a very rare condition in which several risk factors for placental ischemia are associated. Emergency hysterectomy should be considered as salvage initial treatment in such life-threatening situations.