Interstitial pregnancy management: A multicentric analysis of 98 patients from the FRANCOGENT group comparing surgery and medical treatment.

OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.

Elevator-like movements of prestin mediate outer hair cell electromotility.

The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin's transport domain, akin to elevator-type substrate translocation by related solute carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin's piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle.

Management of gynecological cancers in the emergency department: Impact of precariousness and prognostic factors.

OBJECTIVE: The primary objective was to determine the profile of patients consulting in an emergency department and diagnosed with a pelvic cancer. Our secondary objective was to assess the potential impact on this diagnostic trajectory on survival. METHOD: A single-center retrospective study including patients managed for a pelvic cancer between January 2018 and November 2020 in the center Hospitalier Intercommunal de Creteil was conducted. Patients' characteristics were compared based on their diagnostic trajectory (emergency or referred to consultation). Precariousness was assessed using Pascal's tool based on 4 characteristics: being a beneficiary of the former Couverture Maladie Universelle (CMU) or Aide Medicale d'Etat (AME), not having complementary health insurance, being job seeking for more than 6 months and being beneficiary of allowances. A patient was defined as precarious if the Pascal tool was 'TRUE', i.e., at least one positive item. The main socio-demographic and cancer associated factors were analyzed as prognostic factors. RESULTS: Over the inclusion period, among the 283 eligible patients, 37.3 % (87/233) had a diagnosis of cancer following an emergency department visit. There was a significant association between precariousness, rupture of gynecological follow-up, lack of participation in national screening campaigns and the risk of being diagnosed through the emergency pathway for all cancers studied (p = 0.001). There was no difference in terms of stage at diagnostic, management (according to current guidelines), prognostic and overall survival between the two groups. CONCLUSION: Patients in a situation of precariousness are more likely to be diagnosed with cancer in an emergency department. Our study underlines the importance of precariousness as a factor determining the type of diagnostic management of gynecological cancer. Efforts should be made toward improving frail patients to primary care.

A pre-operative radiological score to predict lymph node metastasis in advanced epithelial ovarian cancer.

BACKGROUND: Lymphadenectomy is part of cytoreductive surgery for patients with advanced epithelial ovarian cancer (AEOC) in case of abnormal lymph nodes before and during surgery. The aim of this study was to develop and validate a pre-operative radiological score to predict pelvic and/or para-aortic lymph node metastasis (LNM) in patients with AEOC undergoing cytoreductive surgery. METHODS: We conducted a multicentre retrospective study. The construction sample was composed of 53 patients operated within two referral centers. The validation sample was composed of 39 patients operated in a third referral center. The score was built with a logistic regression model with internal validation by bootstrap. RESULTS: Two variables were associated with the prediction of pelvic and/or para-aortic LNM at computerized tomography (CT) and/or positron emission tomography (PET/CT): "para-aortic lymph node involvement" (adjusted diagnostic odds ratio) (aDOR) = 8.77 95CI [1.42-54.09], p = 0.02) and "colon involvement" (aDOR = 7.97 95CI [1.28-49.58], p = 0.03). Bootstrap procedure showed that the model was stable. The 2-points LNM pre-operative radiological score was derived from these 2 radiological variables and a high-risk group was identified for a score ≥ 1: the probability of pelvic and/or para-aortic LNM was 76%, the specificity was 85.7% 95CI [67.3-96.0] and the positive likelihood ratio was 3.6 95CI [1.4-9.7]. In the validation sample, a score ≥ 1 had a specificity of 78.3% and a LR+ of 1.2. CONCLUSION: LNM pre-operative radiological score could help the surgeon's decision to perform pelvic and para-aortic lymphadenectomy in patients with AEOC undergoing cytoreductive surgery. TRIAL REGISTRATION: The research protocol was approved by the Ethics Committee for Research in Obstetrics and Gynecology (CEROG 2016-GYN 1003).

Impact of the new molecular classification of endometrial cancer: A French cohort study.

OBJECTIVE: To evaluate the potential impact of the latest ESGO guidelines for endometrial cancer with molecular classification on the management strategy in a French cohort. METHODS: All patients treated between January 1st, 2014 and December 31, 2020 for an endometrial cancer at the Centre Hospitalier Intercommunal de Créteil (CHIC, FRANCE) were selected from our prospectively maintained database. All postoperative samples were reviewed to confirm histological subtype, myometrial infiltration, cytonuclear grade and presence of lymphovascular emboli. Analysis of p53, MLH1, MSH2, MSH6, PMS2 genes was performed by immunohistochemistry first then a systematic POLE sequencing was performed to identify gene mutation. The impact of the latest ESGO 2020 guidelines was assessed regarding adjuvant therapy, surgical strategy, and survival. RESULTS: Eighty patients were analyzed, including 70% NSMP (n = 56), 13.75% MSI (n = 11), 10% p53 mutated (n = 8) and 6.25% POLEmut (n = 5). A total of 21 patients (26.3%) were reclassified using the latest ESGO classification. Patients classified at low risk or with advanced / metastatic disease were not reclassified using molecular analysis. Molecular analysis and the latest ESGO classification had the most important impact on patients initially classified at intermediate - high risk that were reclassified in intermediate (10/23) and in low (4/23) risk. Nine patients (11.3%) were overtreated according to the 2020 ESGO classification: six patients in the low - risk group (4 received vaginal brachytherapy and 2 external radiotherapy) and three in the intermediate risk group (3 received external irradiation and 1 received chemotherapy). None of the patients in our cohort would have been undertreated using the 2020 ESGO classification. Patients within the p53 mutated group were the most likely to experience recurrence (37.5%, 3/8) and none of the patients POLE mutated recurred. CONCLUSION: Around one in 4 patients were reclassified in a more accurate prognostic group using molecular diagnosis and the latest ESGO guidelines which could decrease the use of adjuvant therapies to spare morbidity.

Tranexamic acid for the prevention of blood loss after cesarean among women with twins: a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery randomized clinical trial.

BACKGROUND: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies. STUDY DESIGN: This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Total Hysterectomy by Low-Impact Laparoscopy to Decrease Opioids Consumption: A Prospective Cohort Study.

Our objective was to evaluate postoperative pain and opioid consumption in patients undergoing hysterectomy by low-impact laparoscopy and compare these parameters with conventional laparoscopy. We conducted a prospective study in two French gynecological surgery departments from May 2017 to January 2018. The primary endpoint was the intensity of postoperative pain evaluated by a validated numeric rating scale (NRS) and opioid consumption in the postoperative recovery unit on Day 0 and Day 1. Thirty-two patients underwent low-impact laparoscopy and 77 had conventional laparoscopy. Most of the patients (90.6%) who underwent low-impact laparoscopy were managed as outpatients. There was a significantly higher consumption of strong opioids in the conventional compared to the low-impact group on both Day 0 and Day 1: 26.0% and 36.4% vs. 3.1% and 12.5%, respectively (p = 0.02 and p < 0.01). Over two-thirds of the patients in the low-impact group did not require opioids postoperatively. Two factors were predictive of lower postoperative opioid consumption: low-impact laparoscopy (OR 1.38, 95%CI 1.13−1.69, p = 0.002) and a mean intraoperative peritoneum below 10 mmHg (OR 1.25, 95%CI 1.03−1.51). Total hysterectomy by low-impact laparoscopy is feasible in an outpatient setting and is associated with a marked decrease in opioid consumption compared to conventional laparoscopy.

Surgical Determinants of Post Operative Pain in Patients Undergoing Laparoscopic Adnexectomy.

OBJECTIVE: The objective of our study was to determine the main surgical factors associated with postoperative pains in patients undergoing adnexectomy. MATERIAL AND METHODS: Patients that underwent adnexectomy in two French Gynecological centers between July, 2018 and March, 2020 were prospectively included and retrospectively analyzed. The main pre and per operative surgical factors were analyzed to assess their impact on immediate postoperative pain. Analgesic consumption was recorded for each patient and pain was evaluated using the validated numeric rating scale (ranging between 0 and 10). RESULTS: One hundred and seventeen patients underwent laparoscopic adnexectomy. Eighty-four patients (72%) experienced either no or minor postoperative pain (NRS ≤ 2). Seventeen patients (14.5%) required strong opioids (subcutaneous morphine injection) in the immediate postoperative period. The only two parameters that had a significant impact on immediate postoperative pain were the realization of a fascia closure and the duration of pneumoperitoneum longer than 60 minutes. Pneumoperitoneum pressure and size of ports were not significantly correlated with postoperative pain. CONCLUSION: Fascia closure and increased surgical time were significantly associated with immediate postoperative pain and the need for strong opioids consumption. Surgical training to limit prolonged surgeries should be strongly emphasized to lower postoperative pain and limit opioids consumption.

Impact of pre-eclampsia on renal outcome in sickle cell disease patients.

The long-term consequences of pre-eclampsia (PrE) for renal function have never been determined in patients with sickle cell disease (SCD). Between 2008 and 2015, we screened 306 pregnancies in women with SCD and identified 40 with PrE (13%). The control group consisted of 65 pregnant SCD patients without PrE. In multivariable analysis, PrE events were associated with an increase of 1 log of lactate dehydrogenase level (adjusted odds ratio, aOR = 3·83, P = 0·05), a decrease of 10 g/l of haemoglobin levels (aOR = 2·48, P = 0·006) and one or more vaso-occlusive crisis during pregnancy (aOR = 16·68, P = 0·002). Estimated glomerular filtration rate (eGFR) was similar in the two groups at steady state but was significantly lower in the PrE group after one year of follow-up and at last follow-up (130 vs 148 ml/min/1·73 m2 , P < 0·001 and 120 vs 130 ml/min/1·73 m2 , P < 0·001, respectively). In multivariable analysis, eGFR had returned to steady-state levels one year after pregnancy in patients without PrE but continued to decrease in patients with PrE (ß = -18·15 ml/min/1·73 m2 , P < 0·001). This decline was more marked at the end of follow-up (ß = -31·15 ml/min, P < 0·001). In conclusion, PrE episodes are associated with a significant risk of subsequent renal function decline in SCD patients.

Total Versus Free Placental Growth Factor Levels in the Pathogenesis of Preeclampsia.

Elevated circulating sFLT-1 (soluble fms-like tyrosine kinase) and low levels of its ligand, PlGF (placental growth factor), are key characteristics of preeclampsia. However, it is unclear if the low levels of plasma PlGF noted during preeclampsia are due to decreased placental production of PlGF or due to binding of PlGF by increased circulating sFLT-1. Here, we describe a biochemical procedure to dissociate PlGF-sFLT-1 complex ex vivo and when used in conjunction with an immunoassay platform, demonstrate a method to measure total and free PlGF in human blood samples. Using this method, we noted that plasma free PlGF levels were significantly lower in preeclampsia (N=22) than in nonhypertensive controls (N=24; mean, 314 versus 686 pg/mL, P<0.05), but total PlGF levels were not different (mean, 822 versus 800 pg/mL, P=0.49). In contrast, total sFLT-1 levels were significantly higher in preeclampsia than in nonhypertensive controls (mean, 16 957 versus 3029 pg/mL, P<0.01) and sFLT-1 levels correlated with bound PlGF levels (bound PlGF=total PlGF-free PlGF) in these samples (r2=0.68). We confirmed these findings in an independent cohort of subjects (N=49). Furthermore, we did not detect any difference in PlGF mRNA by quantitative polymerase chain reaction or in PlGF protein expression by immunohistochemistry in preeclamptic placentas when compared with nonhypertensive controls. In contrast, sFLT-1 mRNA and protein levels were upregulated in placentas from women with preeclampsia. Taken together with prior studies, our results provide evidence that decrease in circulating PlGF noted during preeclampsia is largely mediated by excess circulating sFLT-1.

Magnetic Resonance and Ultrasound Fusion Imaging to Characterise Ovarian Masses: A Feasibility Study.

BACKGROUND/AIM: Magnetic resonance (MR) and ultrasound (US) fusion imaging (MR-US fusion) is already used to guide prostate biopsies and has been proven accurate for diagnosing cervical cancer. In this study, we aimed to evaluate the feasibility and performance of MR-US fusion for characterizing adnexal masses. PATIENTS AND METHODS: A retrospective study was conducted between 2014 and 2018 including women referred to our Gynaecological Oncology Department for characterization of an adnexal mass (n=106). Performance of MR-US fusion was evaluated in a subgroup of patients who underwent surgery (n=26). Two readers, blinded to final histology, performed and rated US findings according to the International Ovarian Tumor Analysis simple rules score, MR according to Ovarian-Adnexal Reporting Data System Magnetic score, and MR-US fusion through a tailored score. The reference outcome was the final pathology. RESULTS: MR-US fusion had a sensitivity of 100% (95%CI=80-100), specificity of 89% (95%CI=52-99), positive likelihood ratio of 9 (95%CI=1.4-57), and accuracy of 96% (95%CI=80-99). CONCLUSION: MR-US fusion is feasible for characterizing adnexal masses to predict ovarian cancer.

Patients with stage IV epithelial ovarian cancer: understanding the determinants of survival.

BACKGROUND: The most appropriate management for patients with stage IV ovarian cancer remains unclear. Our objective was to understand the main determinants associated with survival and to discuss best surgical management. METHODS: Data of 1038 patients with confirmed ovarian cancer treated between 1996 and 2016 were extracted from maintained databases of 7 French referral gynecologic oncology institutions. Patients with stage IV diseases were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariable analysis, was used to account for the influence of multiple variables. RESULTS: Two hundred and eight patients met our inclusion criteria: 65 (31.3%) never underwent debulking surgery, 52 (25%) underwent primary debulking surgery (PDS) and 91 (43.8%) neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS). Patients not operated had a significantly worse overall survival than patients that underwent PDS or NACT-IDS (p < 0.001). In multivariable analysis, three factors were independent predictors of survival: upfront surgery (HR 0.32 95% CI 0.14-0.71, p = 0.005), postoperative residual disease = 0 (HR 0.37 95% CI 0.18-0.75, p = 0.006) and association of Carboplatin and Paclitaxel regimen (HR 0.45 95% CI 0.25-0.80, p = 0.007). CONCLUSIONS: Presence of distant metastases should not refrain surgeons from performing radical procedures, whenever the patient is able to tolerate. Maximal surgical efforts should be done to minimize residual disease as it is the main determinant of survival.

Added-Value of Endometrial Biopsy in the Diagnostic and Therapeutic Strategy for Pelvic Actinomycosis.

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4-4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

Associated Lichen Sclerosis Increases the Risk of Lymph Node Metastases of Vulvar Cancer.

The most important prognostic factor in vulvar cancer is inguinal lymph node status at the time of diagnosis, even in locally advanced vulvar tumors. The aim of our study was to identify the risk factors of lymph node involvement in these women, especially the impact of lichen sclerosis (LS). We conducted a retrospective population-based cross-sectional study in two French referral gynecologic oncology institutions. We included all women diagnosed with a primary invasive vulvar cancer. Epithelial alteration adjacent to the invasive carcinoma was found in 96.8% (n = 395). The most frequently associated was LS in 27.7% (n = 113). In univariate analysis, LS (p = 0.009); usual type VIN (p = 0.04); tumor size >2 cm and/or local extension to vagina, urethra or anus (p < 0.01), positive margins (p < 0.01), thickness (p < 0.01) and lymphovascular space invasion (LVSI) (p < 0.01) were significantly associated with lymph node involvement. In multivariate analysis, only LS (OR 2.3, 95% CI [1.2-4.3]) and LVSI (OR 5.6, 95% CI [1.7-18.6]) remained significantly associated with positive lymph node. LS was significantly associated with older patients (p = 0.005), anterior localization (p = 0.017) and local extension (tumor size > 2 cm: p = 0.001). LS surrounding vulvar cancer is an independent factor of lymph node involvement, with local extension and LVSI.

Urinary Placental Growth Factor for Prediction of Placental Adverse Outcomes in High-Risk Pregnancies.

OBJECTIVE: To evaluate whether urinary levels of placental growth factor (PlGF) during pregnancy are associated with the subsequent development of composite adverse outcomes (preeclampsia, fetal growth restriction, placental abruption, perinatal death, maternal death) occurring at less than 34 weeks of gestation. METHODS: This is a preplanned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive either low-molecular-weight (LMW) heparin or aspirin alone. For this substudy we measured urinary levels of PlGF and urinary creatinine at the following gestational windows: 10-13 6/7, 14-17 6/7, 18-21 6/7, 22-25 6/7, 26-29 6/7, 30-33 6/7, and 34-37 6/7 weeks of gestation. RESULTS: Urine samples were available from 187 patients: LMW heparin plus aspirin (n=93) and aspirin alone (n=94). The two groups had comparable baseline characteristics and had similar adverse composite outcomes at less than 34 weeks of gestation (14/93 [15.1%] vs 11/94 [11.7%]; P=.50). There were no significant differences in urine PlGF levels in the patients who received LMW heparin plus aspirin compared with those who received aspirin alone. However, median [interquartile range] urinary PlGF/creatinine concentrations (pg/mg) measured at mid-pregnancy (22-26 weeks of gestation) were significantly lower among women who developed composite adverse outcome at less than 34 weeks of gestation (42.7 [32.4-80.8] vs 255.6 [118.7-391.8] P<.001) and significantly lower among women who developed preeclampsia at less than 34 weeks of gestation (42.7 [27.5-80.7] vs 244.6 [112.9-390.6] P<.001). For a fixed false-positive rate of 10% the sensitivity of urinary PlGF concentrations at mid-pregnancy was 75.2% (area under the curve 0.93) for the subsequent development of composite adverse outcomes. CONCLUSION: Decreased urinary PlGF at mid-gestation (22-26 weeks of gestation) is associated with the subsequent development of preeclampsia-related adverse outcomes at less than 34 weeks of gestation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00986765.

Therapeutic value of surgical paraaortic staging in locally advanced cervical cancer: a multicenter cohort analysis from the FRANCOGYN study group.

BACKGROUND: The prognostic impact of surgical paraaortic staging remains unclear in patients with locally advanced cervical cancer (LACC). The objective of our study was to evaluate the survival impact of surgical staging in patients with LACC and no evidence of paraaortic lymph node (PALN) metastasis on pre-operative imaging work-up. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with locally advanced disease (IB2 or more) treated by concurrent chemoradiation therapy (CRT) and no evidence of paraaortic metastasis on pre-operative imaging work-up were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables. RESULTS: Six hundred and forty-seven patients were included, 377 (58.3%) with surgical staging and 270 (41.7%) without, with a mean follow up of 38.1 months (QI 13.0-56.0). Pathologic analysis revealed positive lymph nodes in 47 patients (12.5%). In multivariate model analysis, surgical staging remained an independent prognostic factor for DFS (OR 0.64, CI 95% 0.46-0.89, p = 0.008) and OS (OR 0.43, CI 95% 0.27-0.68, p < 0.001). The other significant parameter in multivariate analysis for both DFS and OS was treatment by intracavitary brachytherapy (OR respectively of 0.7 (0.5-1.0) and 0.6 (0.4-0.9), p < 0.05). CONCLUSION: Nodal surgical staging had an independent positive impact on survival in patients with LACC treated with CRT with no evidence of metastatic PALN on imaging.

LDL-apheresis to decrease sFlt-1 during early severe preeclampsia: Report of two cases from a discontinued phase II trial.

OBJECTIVE: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival. STUDY DESIGN: A phase II prospective study. Adult women were included if they had very early (<26 weeks of gestation) preeclampsia without severe (<5th percentile) intra-uterine growth retardation. Treatment consisted of two weekly sessions (90 min each) of LDL-apheresis of whole blood. The primary endpoint was the status of the baby (dead or living) at 6 months post-delivery. Sample size and stopping rules were calculated assuming a desired success rate of at least 90%. RESULTS: The study was interrupted for safety reasons after the inclusion of two patients: both developed secondary uncontrolled hypertension and blurred vision during the first week of treatment. The first neonate, born at 25 + 3 weeks of gestation, died of sepsis at day 5; the second, born at 26 + 2 weeks of gestation, is still alive and well. In these two patients, the impact of apheresis sessions on sFlt1 concentrations was inconsistent. CONCLUSION: LDL-apheresis did not result in the prolongation of pregnancy in this phase II trial. Further studies will be needed to delineate the appropriate contours of this therapeutic strategy.

Identification of a low risk population for parametrial invasion in patients with early-stage cervical cancer.

BACKGROUND: Recent studies have challenged radical procedures for less extensive surgery in selected patients with early-stage cervical cancer at low risk of parametrial invasion. Our objective was to identify a subgroup of patients at low risk of parametrial invasion among women having undergone surgical treatment. METHODS: Data of 1447 patients with cervical cancer treated between 1996 and 2016 were extracted from maintained databases of 10 French University hospitals. Patients with early-stage (IA2-IIA) disease treated by radical surgery including hysterectomy and trachelectomy, were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariate analysis, was used to account for the influence of multiple variables. RESULTS: Out of the 263 patients included for analysis, on final pathology analysis 28 (10.6%) had parametrial invasion and 235 (89.4%) did not. Factors significantly associated with parametrial invasion on multivariate analysis were: age > 65 years, tumor > 30 mm in diameter measured by MRI, lymphovascular space invasion (LVSI) on pathologic analysis. Among the 235 patients with negative pelvic lymph nodes, parametrial disease was seen in only 7.6% compared with 30.8% of those with positive pelvic nodes (p < 0.001). In a subgroup of patients presenting tumors < 30 mm, negative pelvic status and no LVSI, the risk of parametrial invasion fell to 0.6% (1/173 patients). CONCLUSION: Our analysis suggests that there is a subgroup of patients at very low risk of parametrial invasion, potentially eligible for less radical procedures.

Identification of micro-RNA expression profile related to recurrence in women with ESMO low-risk endometrial cancer.

BACKGROUND: Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. METHODS: MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R-), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. RESULTS: The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R- women. Women with a micro-RNA-184 fold change < 0.083 were more likely to show recurrence (n = 6; 66%) compared to those with a micro-RNA-184 fold change > 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change < 0.56 were more likely to show recurrence (n = 5; 100%) compared to those with a micro-RNA-196 fold change > 0.56 (n = 2; 13%), p = 0.001. CONCLUSIONS: These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.