Abstract
Use of both patent blue and a radioisotope to locate, and reduce the risk of sentinel lymph node (SLN) detection failure in breast cancer is recommended, but drawbacks commonly lead to using ...only a radioisotope. An alternative method would therefore be valuable. This randomized, controlled study in 99 patients compared SLN detection using
99m
technetium (Tc) alone versus Tc combined with indocyanine green (ICG). The primary endpoint was the SLN identification rate. The primary outcome measure was the number of patients with <2 SLN detected. One SLN was detected in 44.0% of patients in the dual detection group and 40.8% in the
99m
Tc alone group (RR = 1.08 (95% CI 0.68; 1.72), p = 0.84). A mean (±SD) of 2.14 ± 1.23 SLN were identified in the dual detection group
vs
. 1.77 ± 0.85 using Tc alone (
p
= 0.09). Eight-five (78.7%) SLN were both ICG+ and TC+, 15 (13.9%) ICG+ and Tc−, and 7 (6.5%) ICG− and Tc+. SLN detected were ICG-positive in 92.6% of patients and
99m
Tc-positive in 85.2% with. No adverse event related to ICG injection was recorded. Dual detection of SLN using ICG and radioisotope is reliable and sensitive but was not superior to isotope alone in successfully locating SLN in our pilot randomized trial.
Background
Mammary and extra-mammary Paget disease is a rare form of intra-epithelial glandular neoplasm which is characteristically recurrent and necessitates multiple excisions that have an ...important impact on morbidity. Local immuno-modulating treatments have been applied with promising results, but the local immune markers of Paget disease have not been studied.
Aim of the study
To investigate the local immune micro-environment of Paget disease.
Materials and methods
Sixty-four specimens from 41 patients, including cases with multiple recurrences and underlying primary neoplasm, have been studied for their expression of CD3, PD-L1 and CTLA-4.
Results
Nineteen cases were mammary; 22 were extra-mammary and involved the vulva, the anus, the inguinal region and the lower extremity. PD-L1 was not expressed by any neoplastic lesion or the associated lymphocytes. CTLA-4 expression was found in nine cases. Higher stromal CD3 expression and moderate levels of intra-epithelial CD3 expression were present in most cases. Biopsies, subsequent excision specimens and recurrences showed the same immunohistochemical profile of CD3 and PD-L1, although there were different levels of CTLA-4 in a few cases. The underlying lesions in mammary Paget disease showed the same immunohistochemical profile as the intra-epithelial neoplastic cells. The expression of the markers did not correlate with age, sex, localization or recurrence.
Conclusion
Paget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression.
It has been suggested that a primary tumor can "prepare" the draining of lymph nodes to "better accommodate" future metastatic cells, thus implying the presence of a premetastatic lymph node niche. ...However, this phenomenon remains unclear in gynecological cancers. The aim of this study was to evaluate lymph-node draining in gynecological cancers for premetastatic niche factors, such as myeloid-derived suppressor cells (MDSCs), immunosuppressive macrophages, cytotoxic T cells, immuno-modulatory molecules, and factors of the extracellular matrix. This is a monocentric retrospective study of patients who underwent lymph-node excision during their gynecological-cancer treatment. In all, 63 non-metastatic pelvic or inguinal lymph nodes, 25 non-metastatic para-aortic lymph nodes, 13 metastatic lymph nodes, and 21 non-cancer-associated lymph nodes (normal controls) were compared for the immunohistochemical presence of CD8 cytotoxic T cells, CD163 M2 macrophages, S100A8/A9 MDSCs, PD-L1+ immune cells, and tenascin-C, which is a matrix remodeling factor. PD-L1-positive immune cells were significantly higher in the control group, in comparison to the regional and distant cancer-draining lymph nodes. Tenascin-C was higher in metastatic lymph nodes than in both non-metastatic nodes and control lymph nodes. Vulvar cancer-draining lymph nodes showed higher PD-L1 values than endometrial cancer and cervical cancer-draining lymph nodes. Endometrial cancer-draining nodes had higher CD163 values and lower CD8 values, compared to vulvar cancer-draining nodes. Regarding regional draining nodes in low- and high-grade endometrial tumors, the former showed lower S100A8/A9 and CD163 values. Gynecological cancer-draining lymph nodes are generally immunocompetent, but vulvar cancer draining nodes, as well as high-grade endometrial cancer draining nodes, are more susceptible to harboring premetastatic niche factors.
Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of ...vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2).
This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section.
In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone.
ClinicalTrials.gov NCT02907060.
This study aimed to assess the application of the French guidelines for pregnancies in Turner syndrome (TS) and their impact on perinatal prognosis.
We performed a French multi-center retrospective ...study (14 centers), including TS pregnant patients (spontaneously or by Assisted Reproductive Technology (ART)) between January 2006 and July 2017.
Only clinical pregnancies were analyzed. The adjustment of medical follow-up modalities to French guidelines was evaluated for all pregnancies after 2009. Pregnancies from oocyte donation (OD) after 2009 were compared to those of a cohort of TS pregnancies obtained by OD before 2009, which were reported by the French Study Group for Oocyte Donation.
One hundred seventy pregnancies in 103 patients were included: 35 spontaneous, 5 by means of intra-conjugal ART, and 130 with OD. No serious maternal complications were observed. We reported two stillbirths and one intra uterine fetal death.
The French guidelines were partially respected. The preconceptional assessment was carried out in 74% of cases. Cardiology follow-up during pregnancy was performed in accordance with guidelines in 74% of patients. Postpartum cardiac ultrasonography was performed in 45% of pregnancies but only in 11% within 8 days post-partum.
When compared to the 2009 historical cohort, the rates of high blood pressure (19% vs. 38%; p < 0.005) pre-eclampsia (8% vs. 21%; p < 0.005) and prematurity <35 weeks (15% vs 38%; p < 0.0001) were lower.
The implementation of guidelines has allowed the standardization of TS pregnancy care and improved perinatal indicators for both mothers and children. However, an effort must be done, in a postpartum survey.
Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for adverse pregnancy, delivery and birth outcomes. Pregnancy is an ideal moment for nutritional ...interventions in order to establish healthier lifestyle behaviors in women at high risk of obstetric and neonatal complications.
Electronic-Personalized Program for Obesity during Pregnancy to Improve Delivery (ePPOP-ID) is an open multicenter randomized controlled trial which will assess the efficacy of an e-health web-based platform offering a personalized lifestyle program to obese pregnant women in order to reduce the rate of labor procedures and delivery interventions in comparison to standard care. A total of 860 eligible pregnant women will be recruited in 18 centers in France between 12 and 22 weeks of gestation, randomized into the intervention or the control arm and followed until 10 weeks of postpartum. The intervention is based on nutrition, eating behavior, physical activity, motivation and well-being advices in which personalization is central, as well as the use of a mobile/tablet application. Inputs includes data from the medical record of participants (medical history, anthropometric data), from the web platform (questionnaires on dietary habits, eating behavior, physical activity and motivation in both groups), and adherence to the program (time of connection for the intervention group only). Data are collected at inclusion, 32 weeks, delivery and 10 weeks postpartum. As primary outcome, we will use a composite endpoint score of obstetrical interventions during labor and delivery, defined as caesarean section and instrumental delivery (forceps and vacuum extractor). Secondary outcomes will consist of data routinely collected as part of usual antenatal and perinatal care, such as GWG, hypertension, preeclampsia, as well as fetal and neonatal outcomes including premature birth, gestational age at birth, birth weight, macrosomia, Apgar score, arterial umbilical cord pH, neonatal traumatism, hyperbilirubinemia, respiratory distress syndrome, transfer in neonatal intensive care unit, and neonatal adiposity. Post-natal outcomes will be duration of breastfeeding, maternal weight retention and child weight at postnatal visit.
The findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy.
ClinicalTrials.gov Identifier: NCT02924636 / October 5th 2016.
Administration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of ...enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18-0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.
IntroductionRecurrent miscarriage (RM), defined by three or more consecutive losses during the first trimester of pregnancy, affects 1%–2% of fertile couples. Standard investigations fail to reveal ...any apparent cause in ~50% of couples. However, on the basis of animal models and clinical studies, several hypotheses have been put forward concerning underlying mechanisms of RM: altered ovarian reserve, progesterone defect, thrombotic and/or endothelial dysfunction and immunological disturbances. Nonetheless, no study has yet reached conclusive beneficial clinical evidence for a potential treatment in unexplained RM. Hydroxychloroquine (HCQ) is a molecule with extensive safety data during pregnancy. The pharmacological properties of HCQ (eg, antithrombotic, vascular protective, immunomodulatory, improved glucose tolerance, lipidlowering and anti-infectious) could be effective against some mechanisms of unexplained RM. Furthermore, eventhough clinical benefit of HCQ is suggested in prevention of thrombotic and late obstetric events in antiphospholipid (APL) syndrome, there are no data suggesting the benefit of HCQ in RM in the presence of APL antibodies.Methods and analysisTaken all together and given the low cost of HCQ, the aim of this multicentre, randomised, placebo-controlled, double-blind study is to investigate whether HCQ would improve the live birth rate in women with RM, irrespective of maternal thrombophilic status: (1) no known thrombophilia, (2) inherited thrombophilia or (3) APL antibodies. The primary end point is a live and viable birth. After confirming eligibility and obtaining consent, 300 non-pregnant women will be randomised into two parallel groups for a daily oral treatment (HCQ 400 mg or placebo), initiated before conception and stopped at 10 weeks’ gestation. If pregnancy does not occur after 1 year, the treatment will be stopped.Ethics and disseminationAgreement from the French National Public Health and Drug Security Agency (160765A-22) and ethical approval from the Committee for the Protection of Persons of NORD-OUEST I (2016-001330-97) have been obtained.Trial registration numbersNCT0316513; Pre-results.
The aim of this study was to assess the outcome and the prognosis factors of uterine and ovarian carcinosarcomas.
From January 1993 to January 2010, data from 68 consecutively treated patients with ...uterine (n=59) and ovarian (n=9) carcinosarcomas were retrospectively analyzed in a single French comprehensive cancer center.
The median follow-up was 24.2 months (interquartile range IQR: 13.5 to 54.6). The median age was 69 years (IQR: 63 to 77). Patients were classified as FIGO stage I (n=28; 41%) and FIGO stage II to IV (n=40; 59%), respectively. There were 33 (49%) and 29 (43%) homologous and heterologous type, respectively. The median disease-free survival and overall survival were 21.9 months (IQR: 7.9 to 22.3) and 27.1 months (IQR: 14.5 to 72), respectively. No statistical differences of survival were reported concerning the initial location of the carcinosarcoma (uterine vs. ovarian). Radiation therapy (hazards ratio HR=0.3; 95% confidence interval CI, 0.16-0.67) and FIGO stage I (HR=0.4; 95% CI, 0.17-0.9) were associated with an increased disease-free survival. Homologous type (HR=3; 95% CI, 1.4-6.3) and FIGO stage II to IV (HR=2.64; 95% CI, 1.3-5.4) were associated with a decreased overall survival. There was no survival improvement for the 12% of patients receiving a multimodal adjuvant therapy.
Uterine and ovary carcinosarcomas present a worse prognosis. On the basis of the present study data, although it should be prospectively confirmed, a sequential or multimodal adjuvant therapy should be proposed to patients with early-stage uterine and ovary carcinosarcomas.
During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of ...placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies (P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50-17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs (P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs (P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC.
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