Relationship between the oxidative status and the tumor growth in transplanted triple-negative 4T1 breast tumor mice after oral administration of rhenium(I)-diselenoether.

BACKGROUND: Selective inhibitory effects of rhenium(I)-diselenoether (Re-diSe) were observed in cultured breast malignant cells. They were attributed to a decrease in Reactive Oxygen Species (ROS) production. A concomitant decrease in the production of Transforming Growth Factor-beta (TGFß1), Insulin Growth Factor 1 (IGF1), and Vascular Endothelial Growth Factor A (VEGFA) by the malignant cells was also observed. AIM: The study aimed to investigate the anti-tumor effects of Re-diSe on mice bearing 4T1 breast tumors, an experimental model of triple-negative breast cancer, and correlate them with several biomarkers. MATERIAL AND METHODS: 4T1 mammary breast cancer cells were orthotopically inoculated into syngenic BALB/c Jack mice. Different doses of Re-diSe (1, 10, and 60 mg/kg) were administered orally for 23 consecutive days to assess the efficacy and toxicity. The oxidative status was evaluated by assaying Advanced Oxidative Protein Products (AOPP), and by the dinitrophenylhydrazone (DNPH) test in plasma of healthy mice, non-treated tumor-bearing mice (controls), treated tumor-bearing mice, and tumors in all tumor-bearing mice. Tumor necrosis factor (TNFα), VEGFA, VEGFB, TGFß1, Interferon, and selenoprotein P (selenoP) were selected as biomarkers. RESULTS: Doses of 1 and 10 mg/kg did not affect the tumor weights. There was a significant increase in the tumor weights in mice treated with the maximum dose of 60 mg/kg, concomitantly with a significant decrease in AOPP, TNFα, and TGFß1 in the tumors. SelenoP concentrations increased in the plasma but not in the tumors. CONCLUSION: We did not confirm the anti-tumor activity of the Re-diSe compound in this experiment. However, the transplantation of the tumor cells did not induce an expected pro-oxidative status without any increase of the oxidative biomarkers in the plasma of controls compared to healthy mice. This condition could be essential to evaluate the effect of an antioxidant drug. The choice of the experimental model will be primordial to assess the effects of the Re-diSe compound in further studies.

Accuracy of prenatal screening for congenital heart disease in population: A retrospective study in Southern France.

Congenital heart diseases (CHDs) are the most common congenital malformations. The objective of our study was to evaluate the prenatal screening accuracy of congenital heart disease (CHD) in Southern France and to evaluate the impact of a prenatal diagnosis on pregnancies outcomes and neonatal outcomes. We performed a bicentric, retrospective observational study in the southern region over 4 years was conducted between 1 January 2014 and 31 December 2017. All foetuses and children under one year of age with CHD monitored in the UTHs (University Teaching Hospitals) in Marseille and Nice were included. CHD cases were divided into 3 groups: group 1, those with no possible options for anatomical repair; group 2, those with anatomical repair possibilities but that may require neonatal cardiologic management; and group 3, those with anatomical repair possibilities that do not require an emergency neonatal procedure. Among the 249070 deliveries during the study period, 677 CHD cases were included in the study. The overall prenatal screening rate was 71.5%. The screening rates were 97.8%, 63.6%, and 65.9% for groups 1, 2 and 3, respectively. Among group 2 CHD cases, 80% of the transpositions of the great arteries, 56% of the aortic coarctations, and 20% of the total anomalous pulmonary venous returns were detected during the prenatal period. A genetic anomaly was found in 16% of CHD cases. The overall mortality rate was 11.3% with a higher death rate in cases of prenatal screening (17.2% versus 2.1%; p < 0.001). However, when focusing only on children who died of CHD, prenatal screening did not create an impact (56.6% versus 100%, p = 0,140). Our data showed that the prenatal screening rate of CHD appears satisfactory in Southern France. Nevertheless, it could be improved for some CHD. This study did not find any benefit in terms of mortality from prenatal screening for CHD.

Immunosuppressive Tumor Microenvironment Status and Histological Grading of Endometrial Carcinoma.

The recent successes of new cancer immunotherapy approaches have led to investigate their relevance in the context of the Endometrial Carcinoma (EC). These therapies, that take the tumor-induced immunosuppressive microenvironment into account, target the tumor immune escape, in particular the inhibitory receptors involved in the regulation of the effector T cells' activity (immune checkpoints). The aim of this study was to identify, in ECs, differences in intergrades immune status that could contribute to the differences in tumor aggressiveness, and could also be used as theranostic tools. The immune status of tumors was assessed by quantitative real-time PCR. We analyzed the expression of specific genes associated to specific leukocytes subpopulations and the expression of reporting genes associated with the tumor escape/resistance. This study highlights significant differences in the EC intergrades immune status especially the tumor-infiltrating cell types and their activation status as well as in the molecular factors produced by the environment. The immune microenvironment of grade 1 ECs hints at a robust tumoricidal milieu while that of higher grades is more evocative of a tolerogenic milieu. This genes-based immunological monitoring of tumors that easily highlights significant intergrade differences relating to the density, composition and functional state of the leukocyte infiltrate, could give solid arguments for choosing the best therapeutic options, especially those targeting immune checkpoints. Moreover it could enable an easy adaptation of individual treatment approaches for each patient.

The Pubic Diastasis Measurement, a Key Element for the Diagnosis, Management, and Prognosis of the Bladder Exstrophy.

OBJECTIVE: To demonstrate the feasibility of measuring the fetal pubic diastasis (PD) distance on antenatal ultrasound in normal fetuses and to compare it to fetuses with bladder exstrophy. METHODS: Firstly, a prospective multicentric study was conducted to determine the feasibility of the PD ultrasound measurement during the second half of pregnancy. Secondly, data from a single center were used to develop a nomogram for PD values in normal fetuses. Thirdly, retrospective PD measurements were collected from fetuses with bladder exstrophy, diagnosed in seven French Multidisciplinary Centers for Prenatal Diagnosis (MCPDs). RESULTS: Operators from several MCPDs examined 868 fetuses and found that overall PD ultrasound measurement was feasible in 71% of cases and that the ossification of pubic points increased to be always visible from 27 weeks of gestation onward. Performed in a single center by a referring operator on 1,539 fetuses, the feasibility reached 94.74%. Both set of measurements were concordant (mean PD distance value of 5.42 ± 1.8 mm). Interestingly, all 23 fetuses with bladder exstrophy showed a significantly larger PD distance (mean 15.74 ± 3.9 mm). CONCLUSION: PD measurement in the fetus is feasible and reliable in the second half of gestation and can be used to support the antenatal diagnosis of bladder exstrophy with PD values exceeding 10 mm.

Brachytherapy and fertility.

Fertility is a major part of the global care of patients treated for cancer. A new discipline known as oncofertility has emerged in some countries. Although the relationship between chemotherapy and external radiotherapy and fertility has been studied and reported, there is only scarce data available on brachytherapy. This systematic review aims to report available knowledge on the impact of brachytherapy on fertility. Specific consultations should be considered before brachytherapy to inform patients about their fertility preservation options.

Development and validation of an objective structured assessment of technical skill tool for the practice of breech presentation delivery.

OBJECTIVE: To develop and test the validity of an Objective Structured Assessment of Technical Skills (OSATS) tool for breech presentation delivery. MATERIALS AND METHODS: Monocentric prospective study conducted in the Department of Gynecology, Obstetrics, Fetal Medicine and Reproductive Medicine at the University Hospital of Nice. The study consisted of two parts, the development of the OSATS scoring system and its objective validation. Several experts in obstetrics from university hospital centers and private French hospitals were invited to participate in the development phase of the scoring system. For the validation phase, we formed a group of 20 novices and a group of 20 experts, who had to perform a breech presentation delivery on a simulator, according to a standardized scenario. Each participant was filmed and two experts would then evaluate their performance by viewing anonymized videos and using the OSATS score. RESULTS: The scores obtained by the expert group were significantly higher than those of the novice group, with a total score of 21.73/25 versus 6.95/25 (p < 0.0001), a task-specific score of 87.2/110 versus 44.3/110 (p < 0.0001) and an overall score of 108.93/135 versus 51.25/135 (p < 0.0001), respectively. CONCLUSION: The OSATS score developed in this study for breech presentation delivery is a reliable model to assess the competence level in procedural skills using a simulator.

Effect of Neoadjuvant Chemotherapy on the Surgical Treatment of Patients With Locally Advanced Breast Cancer Requiring Initial Mastectomy.

BACKGROUND: The aim of this study was to assess the rate of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (nCT) in patients for whom mastectomy (MT) was, initially, the only conceivable surgical option. PATIENTS AND METHODS: Between 2007 and 2012, 168 patients from a single center received nCT. Among these patients, we focused on the ones who received nCT (n = 119, [70.8%]) to decrease tumor size and thus to potentially allow a conservative surgical treatment. For these patients, MT was initially the only possible surgical treatment. RESULTS: Among the 119 patients included, 118 presented with an invasive ductal carcinoma. The mean tumor size before nCT, measured using magnetic resonance imaging, was 41.6 mm (range, 15-110 mm) and 25.3 mm (range, 0-90 mm) after nCT. Eighty-six patients (72.3%) underwent BCS, and oncoplastic techniques were used in 29 patients (33.6%). Only 4.3% (5 patients) of patients who were treated with BCS needed additional surgery because of positive surgical margins. The median follow-up was 41.1 months (95% confidence interval [CI], 35.2-48.3). Five-year overall survival after BCS and MT were 77% (95% CI, 63-92) and 77% (95% CI, 63-95) respectively. Five-year disease-free survival after BCS and MT were 74% (95% CI, 64-86) and 59% (95% CI, 40-89) (not significant), respectively. CONCLUSION: nCT for selective patients with "chemosensitive" breast tumor leads to a significant "MT to BCS" conversion rate. The type of surgery does not seem to affect the patient's overall and disease-free survival rates. Oncoplastic procedures can help to extend BCS after nCT.

Development and validation of an objective structured assessment of technical skill tool for the practice of vertex presentation delivery.

OBJECTIVE: To develop and test the validity of an objective structured assessment of technical skill (OSATS) tool for vertex presentation delivery simulations. MATERIALS AND METHODS: Monocentric prospective study conducted in the Department of Gynecology, Obstetrics, Fetal Medicine and Reproductive Biology at the University Hospital of Nice. The study consisted of two parts, the development of the scoring system and then its validation. Experts in obstetrics from several academic institutions and private French hospitals were invited to participate in the development phase of the scoring system. For the validation phase, we formed a group of 20 novices and a group of 20 experts, who performed a childbirth simulation according to a standard scenario. Each participant was filmed and then two experts evaluated their performance with the OSATS score by viewing anonymized videos. RESULTS: The scores obtained by the expert group were significantly higher than those of the novice group, whether we compared the total score or each part of the score (task-specific or global) independently. We obtained a p value of 0.03 for the total score, p = 0.036 for the task-specific score, and p < 0.001 for the overall score. CONCLUSION: The OSATS score developed in this study for vertex presentation delivery is a reliable mean to assess the medical students' competence in procedural skills using a simulator.