Aryl Hydrocarbon Receptor and Its Diverse Ligands and Functions: An Exposome Receptor.

The aryl hydrocarbon receptor (AhR) is a transcriptional factor that regulates multiple functions following its activation by a variety of ligands, including xenobiotics, natural products, microbiome metabolites, and endogenous molecules. Because of this diversity, the AhR constitutes an exposome receptor. One of its main functions is to regulate several lines of defense against chemical insults and bacterial infections. Indeed, in addition to its well-established detoxication function, it has several functions at physiological barriers, and it plays a critical role in immunomodulation. The AhR is also involved in the development of several organs and their homeostatic maintenance. Its activity depends on the type of ligand and on the time frame of the receptor activation, which can be either sustained or transient, leading in some cases to opposite modes of regulations as illustrated in the regulation of different cancer pathways. The development of selective modulators and their pharmacological characterization are important areas of research.

What is the most pertinent definition of malnutrition in epithelial ovarian cancer to assess morbidity and mortality?

INTRODUCTION: Malnutrition is common in ovarian cancer and is a major cause of morbidity and mortality. We aimed to define the most pertinent way to assess malnutrition in patients with epithelial ovarian cancer (EOC) in order to study its impact on morbidity (intra and post-operative complications) and survival (OS, overall survival and RFS, recurrence-free survival). METHODS: We retrospectively included all patients with EOC from 2003 to 2020. Nutritional status was assessed using the weight loss at diagnosis (more or <5%), albuminemia, the Nutritional Risk Index (NRI), and the Malnutrition Universal Screening Tool (MUST). RESULTS: Six hundred and fifteen patients were included. Among them, 34% declared having lost >5% of their usual weight, 58% had an albuminemia <35 g/L, 86% presented an abnormal NRI and 29% an abnormal MUST score. After univariate analysis, weight loss>5% appeared to be significantly associated with RFS. An abnormal NRI or MUST score were significantly associated with a decrease in OS in univariate analysis. None of the markers of malnutrition studied were correlated with morbidity. CONCLUSION: We were not able to reach a consensus concerning the most accurate definition to define malnutrition and predict morbidity and mortality in EOC. However, this modifiable prognosis factor must be systematically assessed and managed accordingly.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Could uterine conservation be an option in presumed early-stage epithelial ovarian cancer?

PURPOSE: In early-stage epithelial ovarian cancer (EOC), patients usually undergo a hysterectomy. However, in fertility sparing surgery (FSS), carefully selected patients could conserve their uterus. The aim of our study was to evaluate the incidence and epidemiologic characteristics associated with uterine involvement in patients with early-stage EOC, outside of FSS. METHODS: We conducted a retrospective, monocentric, study from 2003 to 2019 and included all patients with a presumed early-stage EOC (FIGO I) who underwent a hysterectomy. The incidence of uterine involvement, predictive factors of uterine involvement, and the impact of uterine involvement on survival (recurrence-free survival and overall survival) were analyzed. RESULTS: Eighty-five patients had an early-stage EOC. Of these, six had an uterine involvement (7%). The populations of patients with or without uterine involvement did not differ except for CA 125 at diagnosis (136 ± 138 versus 356 ± 723, p = 0.04, respectively). No patient or tumor characteristics were predictive of uterine involvement. Uterine involvement was not associated with recurrence-free survival (HR = 1.26, IC95% 0.36-4.4, p = 0.72) or overall survival (HR = 0.7, IC95% 0.1-6.1, p = 0.77). CONCLUSION: Due to the small size of our sample, no conclusion can be drawn, yet it could be hypothesized that, for selected patients, a systematic hysterectomy could be discussed, notably in restaging surgery.

Diagnostic value of indocyanine green fluorescence guided sentinel lymph node biopsy in vulvar cancer: A systematic review.

INTRODUCTION: Sentinel lymph node biopsy (SLN) helps define lymph node status, a major prognostic factor in vulvar cancer. The aim of the current systematic review was to assess the use of indocyanine green (ICG) coupled with near-infrared (NIR) fluorescence imaging in SLN mapping in vulvar cancer in terms of technique used, feasibility and accuracy. DATA SOURCES: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for SLN, ICG and vulvar cancer were combined and restricted to the English language. The final search was performed on May 28, 2020. The primary outcome was to determine if the use of ICG alone in detecting SLN in women with vulvar cancer is as accurate as the gold standard dual labeling technique. RESULTS: Of the 34 studies initially identified, 13 were included for analysis. The SLN detection rate with ICG and NIR fluorescence ranged from 89.7 to 100%. No studies demonstrated the superiority of other detection techniques compared to ICG and NIR imaging. Lower SLN detection rates were found in studies with the most metastatic lymph nodes. No consensus was reached concerning the optimal use of ICG in terms of: injection timing or site; concentrations or volume of ICG; or use of human serum albumin or hybrid tracer. No adverse events were reported. CONCLUSION: ICG for SLN mapping appears to be safe in women with vulvar cancer with a detection rate similar to the current techniques. A large prospective randomized controlled study with optimization of the technique is necessary to homogenize current practice and determine the true value of ICG in vulvar cancer. PROSPERO ID: CRD42020178261.

What can we learn from the 10 mm lymph node size cut-off on the CT in advanced ovarian cancer at the time of interval debulking surgery?

INTRODUCTION: The benefit of a systematic lymphadenectomy is still debated in patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. MATERIEL AND METHODS: A retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005 and 2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. RESULTS: 158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at 'high risk' (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. CONCLUSION: Presence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

Predictive approach in managing voiding dysfunction after surgery for deep endometriosis: a personalized nomogram.

INTRODUCTION AND HYPOTHESIS: The aim was to develop a nomogram based on clinical and surgical factors to predict the likelihood of voiding dysfunction after surgery for deep endometriosis. METHODS: This was a retrospective study of 789 patients (training set) who underwent surgery for deep endometriosis with colorectal involvement from January 2005 through December 2017 at Tenon University Hospital. A multivariate logistic regression analysis of selected risk factors was performed to construct a nomogram to predict postoperative voiding dysfunction. The nomogram was externally validated in 333 patients (validation set) from Rouen University Hospital. RESULTS: Postoperative voiding dysfunction occurred in 23% of the patients (180/789) in the training set. Age, colorectal involvement/management, colpectomy and parametrectomy were the main factors associated with an increased risk of voiding dysfunction and were included in the nomogram. The predictive model had an internal concordance index of 0.79 (95% CI: 0.77-0.81) after the 200 repetitions of bootstrap sample corrections and showed good calibration. The ROC area related to the nomogram for external validation was 0.74 (95% CI: 0.72-0.76). CONCLUSIONS: The nomogram we present here, based on four clinical and imaging characteristics, could be useful in predicting postoperative voiding dysfunction for women undergoing surgery for deep endometriosis. Patients could thus be better informed about this postoperative risk and the surgical strategy adapted according to individual risk. The accuracy of the tool was validated externally but additional validation is required.

Impact of obesity on surgical and oncologic outcomes in patients with endometrial cancer treated with a robotic approach.

AIM: The surgical treatment of endometrial cancer (EC) can be more complicated in obese patients. Robotic surgery could simplify the surgical approach in these patients. The aim of our study was to compare the outcomes of robotic surgery in obese (body mass index ≥30 kg/m2 ) and nonobese patients. METHODS: We performed a retrospective study on patients with EC benefitting from a robotic approach in our institution. The primary outcome was the 5-year overall survival (OS). We also assessed the 5-year recurrence-free survival (RFS), type of surgery, laparotomy conversion rate, adjuvant treatment and postoperative morbidity. RESULTS: We analyzed 175 consecutive patients with EC who underwent robotic surgery, 42 patients with obesity and 133 patients without. The median follow-up length was 37 months [1-120]. The OS rate was 97% in the whole population and the RFS was 74%. Obesity did not impact prognosis. Laparotomy conversion rate was low in both groups (5% in patients with obesity vs 3%, P = 0.619). There were no significant differences in terms of postoperative complications (5 vs 9%, P = 0.738). There were significantly less pelvic lymphadenectomies in patients with obesity (5 vs 12%, P = 0.005). In the subgroup of patients with high-risk EC, rate of lymphadenectomy and of adjuvant treatments did not differ between patients with or without obesity. CONCLUSION: Obese patients with EC can be safely treated with a robotic approach, with a low complication rate and similar oncological outcomes compared to nonobese patients.

Does a pre-operative conization improve disease-free survival in early-stage cervical cancer?

PURPOSE: Ever since the recent findings showing the lack of benefit of minimally invasive surgery (MIS) versus open surgery in early-stage cervical cancer, gynecologists have tried to explain these results. The primary objective of our study was to assess the impact of pre-operative conization on disease-free survival (DFS) in early-stage cervical cancer. The secondary objective was to analyze the peri-operative morbidity associated with a pre-operative conization. METHODS: All patients undergoing a surgical management for early-stage squamous carcinoma or adenocarcinoma cervical cancer (IA1, IA2, IB1 and IB2 FIGO 2018) at a French university hospital from 2004 to 2018 were retrospectively included. We examined the association between conization and DFS using a Cox regression model. We also analyzed the morbidity associated with pre-operative conization. RESULTS: 48.4% (44/91) of the patients had a pre-operative conization (defined by a conization up to 90 days prior to surgery). 86.8% underwent MIS. There was a non-significant increase in the DFS with one patient presenting a recurrence in the conization group (2.3%) and six (12.8%) in the no conization group (log rank = 0.09). In univariate analysis, conization, definitive FIGO stage and pre-operative tumor size were associated with DFS (p < 0.2). Only pre-operative tumor size was significantly associated with DFS in multivariate analysis. There was a non-significant increase of adverse events in the conization group (43.2% in the conization group versus 23.4%, p = 0.06). CONCLUSION: Conization, through a reduction of tumor size, could improve DFS. Carefully selected patients could still benefit from minimally invasive surgery.

Hyperthermic intraperitoneal chemotherapy (HIPEC): Should we look closer at the microenvironment?

The age of cancer as an isolated single-cell concept is now behind us. It is now established that epithelial ovarian cancer, like other cancers, interacts with the healthy bystander cells to influence them and takes advantage of their nutritional, immunological, disseminating and other capacities. This interaction has become a therapeutic target, as shown by the numerous studies on this subject. Intraperitoneal chemo-hyperthermia has been part of the therapeutic armamentarium for some time yet its efficiency in ovarian cancer has only been recently proven in a randomized controlled trial. However, its therapeutic performance is not revolutionary and epithelial ovarian cancer maintains a high mortality. In this review, we studied the impact of HIPEC on the microenvironment and vice versa to determine whether it could be the key to this lukewarm efficacy. We began by exploring the modalities of HIPEC and establishing the reasons that make this treatment topical. Then, we examined its impact on each element of the tumor environment to obtain a global view of the resistance mechanisms at work in HIPEC.

Pre-operative surgical algorithm: sentinel lymph node biopsy as predictor of parametrial involvement in early-stage cervical cancer.

INTRODUCTION: Radical hysterectomy is the gold standard in the management of early-stage cervical cancer. Parametrectomy aims to remove occult disease but is associated with significant surgical morbidity. Avoiding unnecessary parametrectomy in a subset of patients at low risk of parametrial involvement may decrease the incidence of such morbidity. The purpose of this study was to identify patients at low risk of parametrial involvement in early-stage cervical cancer potentially eligible for less radical surgery based on pre-operative criteria and sentinel lymph node (SLN) status. METHODS: We performed an ancillary analysis of data from two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I and II). Patients with International Federation of Gynecology and Obstetrics (FIGO) IA-IIA cervical cancer who underwent primary radical surgery and bilateral SLN mapping were identified between 2005 and 2012 from 25 French oncologic centers. Patients who underwent pre-operative brachytherapy or did not undergo radical surgery (simple trachelectomy, simple hysterectomy, or lymph node staging only) were excluded. RESULTS: Of 174 patients who fullfiled the inclusion criteria, 9 patients (5.2%) had parametrial involvement and 24 patients (13.8%) had positive SLN. Most patients had 2018 FIGO stage IB1 disease (86.1%) and squamous cell carcinomas (68.9%). Parametrial involvement was significantly associated with tumor size ≥20 mm on pelvic magnetic resonance imaging (MRI) (adjusted odds ratio (ORa) 9.30, 95% CI 1.71 to 50.57, p=0.01) and micrometastic or macrometastatic SLN (ORa 8.98, 95% CI 1.59 to 50.84, p=0.01). Of 114 patients with tumors <20 mm on pre-operative MRI and negative SLN after ultrastaging, only one patient had parametrial involvement (0.9%). By triaging patients with both of these criteria in a two-step surgical procedure, unjustified and contra-indicated radical hysterectomy would have been avoided in 65.5% and 8.6% of cases, respectively. CONCLUSIONS: Less radical surgery may be an option for patients with bilateral negative SLN after ultrastaging and tumors <20 mm. SLN status should be integrated into the decision-making process for tailored surgery in early-stage cervical cancer.

Voiding Dysfunction after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: Surgical management of deep endometriosis is associated with a high incidence of lower urinary tract dysfunction. The aim of the current systematic review and meta-analysis was to assess the rates of voiding dysfunction according to colorectal shaving, discoid excision, and segmental resection for deep endometriosis. DATA SOURCES: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. Medical Subject Headings terms for colorectal endometriosis and voiding dysfunction were combined and restricted to the French and English languages. The final search was performed on August 28, 2019. The outcome measured was the occurrence of postoperative voiding dysfunction. METHODS OF STUDY SELECTION: Study Quality Assessment Tools were used to assess the quality of included studies. Studies rated as good and fair were included. Two reviewers independently assessed the quality of each included study, discrepancies were discussed; if consensus was not reached, a third reviewer was consulted. TABULATION, INTEGRATION AND RESULTS: Out of 201 relevant published reports, 51 studies were ultimately reviewed systematically and 13 were included in the meta-analysis. Rectal shaving was statistically less associated with postoperative voiding dysfunction than segmental colorectal resection (Odds ratio [OR] 0.34; 95% confidence intervals [CI], 0.18-0.63; I2 = 0%; p <.001) or discoid excision (OR 0.22; 95% CI, 0.09-0.51; I2 = 0%; p  <.001). No significant difference was noted when comparing discoid excision and segmental colorectal resection (OR 0.74; 95% CI, 0.32-1.69; I2 = 29%; p = .47). Similarly, rectal shaving was associated with a lower risk of self-catheterization >1 month than segmental colorectal resection (OR 0.3; 95% CI, 0.14-0.66; I2 = 0%; p = .003). This outcome was no longer significant when comparing discoid excision and segmental colorectal resection (OR 0.72; 95% CI, 0.4-1.31; I2 = 63%; p = .28). CONCLUSION: Colorectal surgery for endometriosis has a significant impact on urinary function regardless of the technique. However, rectal shaving causes less postoperative voiding dysfunction than discoid excision or segmental resection.

Impact of Sociodemographic Characteristics on the Quality of Care in the Surgical Management of Endometrial Cancer: An Analysis of a National Database in the United States.

INTRODUCTION: Quality of care is an emerging concern, notably in oncology. The aim of the present study was to identify the sociodemographic factors influencing the quality of care in the USA concerning the surgical management of endometrial cancer (EC) through the Surveillance Epidemiology and End Results (SEER) database using already published Belgian quality indicators (QI). METHODS: Using the SEER database 1988-2013, we identified 151,752 patients treated for EC. Six QI were extracted from a Belgian study on quality of care in EC because of their applicability to the SEER. These QI evaluated only the surgical management. We examined the association between sociodemographic characteristics and quality of care with a logistic regression model. We compared our results with those defined as theoretical target by the Belgian initiative and considered a QI to be accurately met if >80% of the population met the indicator, moderately met between 50 and 80%, and poorly met under 50%. RESULTS: Concerning the 6 surgical QIs, one was accurately met, 3 were moderately met, and 2 were poorly met. For example, 73% of the patients with a high-risk EC underwent a pelvic lymphadenectomy. Age over 75 years old, black ethnicity, lower-income group, without partner, and uninsured had a negative impact on adherence to QIs. CONCLUSION: Demographic discrepancies persist in the surgical management of EC, impacting evidence-based care.

Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia.

INTRODUCTION: Early management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a loop electro excision procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. OBJECTIVE: The main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. METHODS: We conducted a retrospective unicentric study between 2009 and 2017. RESULTS: Two hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5 % of laser excisions and 72.7 % of LEEP (p = 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95 %CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95 %CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95 %CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. CONCLUSION: No difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.

Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer.

OBJECTIVE: BRCA1 promoter methylation (BRCA1pm) is suspected to alter prognosis of patients with epithelial ovarian cancer (EOC). We aimed to evaluate the prognostic impact of this epigenetic modification. METHODS: We conducted a retrospective, monocentric study from 11/2006 to 08/2018. Patients with EOC and available status concerning somatic BRCA1/2 mutation and BRCA1pm were included. Three groups were defined: patients without BRCA1/2 mutation or BRCA1pm, patients with BRCA1/2 mutation and patients with BRCA1pm. BRCA1/2 mutations were analyzed in current care settings by next-generation sequencing (NGS). BRCA1pm analysis was assessed and quantified from bisulfite converted DNAs using fluorescent methylation specific polymerase chain reaction (PCR) and fragment analysis. All patients signed a consent form and the study was authorized by a Personal Protection Committee. Descriptive statistics were used to describe groups. Multivariate analysis was performed using the logistic regression model and including the variables that could be known at the time of diagnosis and that were significant at univariate analysis. Survival was compared between the groups. Kaplan-Mayer curves were used to express the differences in survival that were compared using log rank tests. RESULTS: 145 patients were included: 95 (65.5 %) patients without BRCA1/2 mutation or BRCA1pm, 32 (22.1 %) patients with BRCA1/2 mutation, 18 (12.4 %) patients with BRCA1pm. Median survival was decreased in patients with BRCA1pm. Comparison of survival revealed a significant difference in overall survival (p = 0.0078) with a worse prognosis for patients with a BRCA1pm. CONCLUSION: BRCA1pm in patients with EOC is an independent factor associated with a decreased overall survival. SYNOPSIS: BRCA1 promotor methylation in patients with epithelial ovarian cancer is an independent factor associated with a decreased overall survival.

Clinical use of Indocyanine green fluorescence method for sentinel lymph node biopsy in breast cancer in France in 2021.

INTRODUCTION: Indocyanine green (ICG) for axillary sentinel lymph node (SLN) detection in early breast cancer is at least equivalent to radioisotopic and/or colorimetric techniques. This procedure has not yet been recommended by learned societies in France. Following the recent drug approval of Infracyanin ® in this indication, we wished to study the use of ICG in France. METHODS: We conducted a web-based survey among members of multiple French breast cancer societies throughout November 2021. The survey assessed the profile of the respondent, the use or not of ICG for the detection of SLN in breast cancer, the technique used and the opinion of non-users and their expectations on the subject. RESULTS: Seventy-five surgeons participated. More than a third (37 %) have been using ICG for the detection of SLN in breast cancer for 2 to 3 years. Technique was highly variable. According to 82.1 % of the respondents, less than 20 procedures are necessary to master the use of ICG. The main advantage reported for this method is the reduction of organizational constraints. The obstacles to the use of the ICG are the near infra-red camera equipment, but also the lack of validation by the French guidelines. Among non-users, 83 % would like to develop this technique in their center and 72.3 % are interested in training on this subject. CONCLUSION: This work highlights the need for French learned societies to take a stand on this issue but also the need to carry out studies on the technical aspects in order to standardise practices.

Environmental health in medical schools in France: A call from medical students.

OBJECTIVE: Environmental factors contribute to more than 25% of all global disease but as medical student, we consider that environmental health is insufficiently taught. We are not armed for facing patient's questions, prevent diseases linked to environmental exposure and adapt care in susceptible population. MATERIAL AND METHODS: We conducted a national French survey, using a web-based questionnaire from October to November 2021. All medical students were interrogated to assess their knowledge on environmental health and their desire to obtain a specific curriculum on this topic. RESULTS: Two hundred and thirty-two students responded to the survey and most (62.7%) had never had any teaching on environmental health during their medical studies. The majority claimed to have no knowledge on environmental health (63.6%), and most had never been read or seen media content about it (59.2%). Those who had knowledge on environmental health, had been informed through social media, questioning the reliability of this content. Most (87.3%) were ready to take a specific course on environmental health issues during their medical studies in order to better inform their patients with evidence-based medicine and identify at risk population. CONCLUSION: Through a survey, we identified the need and the emergency of implanting a curriculum on environmental medicine in our medical education.

Cigarette smoke and tumor microenvironment copromote aggressiveness of human breast cancer cells.

Breast cancer is a major public health issue and the role of pollutants in promoting breast cancer progression has recently been suggested. We aimed to assess if a mixture of pollutants, cigarette smoke, could favor the aggressivity of breast cancer cells. We also evaluated the impact of the tumor microenvironment, largely represented by adipocytes, in mediating this modification of cell phenotype. Breast cancer cells lines, MCF-7 were cultured using a transwell coculture model with preadipocytes hMADS cells or were cultured alone. Cells were treated with cigarette smoke extract (CSE) and the four conditions: control, treated by CSE, coculture, and coexposure (coculture and CSE) were compared. We analyzed morphological changes, cell migration, resistance to anoikis, stemness, epithelial-to-mesenchymal transition (EMT), and the presence of hormonal receptors in each condition. A complete transcriptomic analysis was carried out to highlight certain pathways. We also assessed whether the aryl hydrocarbon receptor (AhR), a receptor involved in the metabolism of xenobiotics, could mediate these modifications. Several hallmarks of metastasis were specific to the coexposure condition (cell migration, resistance to anoikis, stemness characterized by CD24/CD44 ratios and ALDH1A1 and ALDH1A3 rates) whereas others (morphological changes, EMT, loss of hormonal receptors) could be seen in the coculture condition and were aggravated by CSE (coexposure). Moreover, MCF-7 cells presented a decrease in hormonal receptors, suggesting an endocrine treatment resistance. These results were confirmed by the transcriptomic analysis. We suggest that the AhR could mediate the loss of hormonal receptor and the increase in cell migration.

Patterns of recurrence in surgically treated women for TP53-mutated endometrial carcinomas.

OBJECTIVE: To describe the patterns of recurrence and the prognosis of patients with a recurrent TP53 mutated endometrial carcinoma treated initially by surgery. METHODS: All patients with endometrial carcinoma, treated at hospital European Georges Pompidou between 2001 and 2021 were retrospectively included. Patients were separated into two groups: TP53-mutated and not TP53-mutated (POLE/ultramutated-like (POLEmut), dMMR (mismatch repair-deficient) and NSMP (No specific molecular profile)). We estimated survival using recurrence free survival, overall survival and overall survival from recurrence. The risk of recurrence according to TP53 status and the type of recurrence (locoregional recurrence, peritoneal recurrence, and metastasis) were also compared between the two groups. RESULTS: Two hundred and ninety-one patients with endometrial carcinoma were included. Of these, 57 were TP53-mutated and 234 patients were not TP53-mutated. TP53 mutated patients had the worst recurrence free survival and overall survival (p < 0.001 for each). The hazard rate of recurrence was higher during the first three years for TP53 mutated endometrial carcinoma then tend to join the one of no TP53 mutated. There was a statistical difference between the two groups in terms of cumulative incidence of peritoneal recurrence (p = 0.002). There was, however, no statistical difference in overall survival from recurrence. CONCLUSIONS: TP53-mutated endometrial carcinoma were more likely to experience a recurrence during the first three years and most often peritoneal recurrence compared to not TP53-mutated. TP53 status in endometrial carcinoma could be useful to define follow-up. Further prospective studies are required to assess the predictive impact of TP53 mutation on chemotherapy benefit.