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1.
Annu Rev Pharmacol Toxicol ; 62: 383-404, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34499523

RESUMO

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.


Assuntos
Expossoma , Receptores de Hidrocarboneto Arílico , Homeostase , Humanos , Ligantes , Receptores de Hidrocarboneto Arílico/metabolismo , Xenobióticos/metabolismo
2.
Gynecol Oncol ; 181: 12-19, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38101153

RESUMO

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.


Assuntos
Desnutrição , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/complicações , Estudos Retrospectivos , Avaliação Nutricional , Desnutrição/diagnóstico , Desnutrição/complicações , Estado Nutricional , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Redução de Peso , Morbidade
3.
Am J Obstet Gynecol ; 228(4): 443.e1-443.e10, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36427596

RESUMO

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.


Assuntos
Preservação da Fertilidade , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Colo do Útero/cirurgia , Colo do Útero/patologia , Preservação da Fertilidade/métodos , Resultado da Gravidez , Fatores de Risco , Estadiamento de Neoplasias
4.
BJOG ; 130(12): 1511-1520, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37165717

RESUMO

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.

5.
Arch Gynecol Obstet ; 308(3): 953-960, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37031304

RESUMO

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.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Útero/cirurgia , Útero/patologia
6.
Br J Cancer ; 127(6): 1123-1132, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35752712

RESUMO

BACKGROUND: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD. METHODS: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples). The RNAseq score was applied in independent gynaecological datasets (CARPEM/CPTAC/SCAN/TCGA, N = 4038 samples). Validations used ROC curves, linear regressions and Pearson correlations. Overall survival (OS) analyses used Kaplan-Meier curves and Cox models. RESULTS: In total, 656 genes were commonly up/downregulated with gHRD score in UCEC/BRCA/OV. Upregulated genes were enriched for nuclear/chromatin/DNA-repair processes, while downregulated genes for cytoskeleton (gene ontologies). The RNAseq score correlated with gHRD score in independent gynaecological cancers (R² = 0.4-0.7, Pearson correlation = 0.64-0.86, all P < 10-11), and was predictive of gHRD score >42 (RNAseq HRD profile; AUC = 0.95/0.92/0.78 in UCEC/BRCA/OV). RNAseq HRD profile was associated (i) with better OS in platinum-treated advanced TP53-mutated-UCEC (P < 0.001) and OV (P = 0.013), and (ii) with poorer OS (P < 0.001) and higher benefit of adjuvant chemotherapy in Stage I-III BRCA (interaction test, P < 0.001). CONCLUSIONS: UCEC/BRCA/OV with HRD-associated genomic scars share a common transcriptional profile. RNAseq signatures might be relevant for identifying HRD-gynaecological cancers, for prognostication and for therapeutic decision.


Assuntos
Proteína BRCA2 , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Reparo do DNA , Feminino , Recombinação Homóloga/genética , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
7.
Gynecol Oncol ; 166(2): 269-276, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35643579

RESUMO

INTRODUCTION: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients. METHODS: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included. Patients were categorized as: <70 years (y), >70y without comorbidity (fit), and > 70y with a Charlson comorbidity index>3 (comorbid). Association between high-risk EC (2021-ESGO-ETRO-ESP) or comorbidity, and disease-specific-survival (DSS), was evaluated using Cox model (estimation of cause-specific hazard ratio (CSHR), and Fine-Gray model (subdistribution HR) to account for competing events (death unrelated with EC). RESULTS: Overall, 253 patients were included (median age = 67y, IQR[59-77], median follow-up = 61.5 months, [44.4-76.8]). Among them, 109 (43%) were categorized at high-risk (proportion independent of age), including 67 (26%) who had TP53-mutated tumors. Comorbidity and high-risk group were both associated with all-cause mortality (HR = 4.09, 95%CI[2.29; 7.32] and HR = 3.21, 95%CI [1.69; 6.09], respectively). By multivariate analysis, patients with high-risk EC exhibited poorer DSS, regardless of age/comorbidity (Adjusted-CSHR = 6.62, 95%CI[2.53;17.3]; adjusted-SHR = 6.62 95%CI[2.50;17.5]). Patients>70y-comorbid with high-risk EC had 5-years cumulative incidences of EC-related and EC-unrelated death of 29% and 19%, respectively. In patients <70y, 5-years cumulative incidence of EC-related and EC-unrelated death were 25% and < 1% (one event), respectively. CONCLUSION: High-risk EC patients are exposed to poorer DSS regardless of age/comorbidities, comorbidities and cancer being two cumulative rather than competing risks. Our results suggest that age/comorbidity alone should not lead to underestimate EC-specific survival.


Assuntos
Neoplasias do Endométrio , Idoso , Estudos de Coortes , Comorbidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco
8.
Gynecol Oncol ; 164(3): 596-606, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35033379

RESUMO

BACKGROUND: Despite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems. METHODS: A prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients). A clinically applicable polyA-RNAseq-based work-flow was developed for validation of the signature in a cohort of stage I-IV patients treated in two Hospitals [2010-2017]. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated by multivariable Cox model, adjusted on high-risk prognostic group (2021 ESGO-ESTRO-ESP guidelines: non-endometrioid histology or stage III-IVA orTP53-mutated molecular subgroup). RESULTS: Among 209 patients included in the external validation cohort, 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC = 0.80). Most disease-related deaths occurred in high-risk patients (5-years DSS = 78% (95% CI = [68%-89%]) versus 99% [97%-100%] in patients without high-risk). A composite classifier accounting for the TP53-mutated subgroup and the RNAseq signature identified three classes independently associated with DSS: RNAseq-good prognosis (reference, 5-years DSS = 99%), non-TP53 tumors but with RNAseq-poor prognosis (adjusted-hazard ratio (aHR) = 5.75, 95% CI[1.14-29.0]), and TP53-mutated subgroup (aHR = 5.64 [1.12-28.3]). The model accounting for the high-risk group and the composite classifier predicted DSS with AUC = 0.84, versus AUC = 0.76 without (p = 0.01). CONCLUSION: RNA-seq profiling can provide an additional prognostic information to established classification systems, and warrants validation for potential RNAseq-based therapeutic strategies in EC.


Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Sequenciamento do Exoma
9.
Gynecol Oncol ; 161(2): 436-441, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33551201

RESUMO

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.


Assuntos
Carcinoma/patologia , Corantes Fluorescentes , Verde de Indocianina , Imagem Óptica/métodos , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Neoplasias Vulvares/patologia , Carcinoma/diagnóstico por imagem , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Linfonodo Sentinela/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Neoplasias Vulvares/diagnóstico por imagem
10.
Gynecol Oncol ; 162(3): 667-673, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34217542

RESUMO

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.


Assuntos
Carcinoma Epitelial do Ovário/patologia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Neoplasias Ovarianas/patologia , Idoso , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
11.
Arch Gynecol Obstet ; 303(1): 231-239, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964259

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/terapia , Conização/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
12.
Environ Health ; 19(1): 117, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203443

RESUMO

Breast cancer (BC) is one of the most common causes of cancer in the world and the second leading cause of cancer deaths among women. Mortality is associated mainly with the development of metastases. Identification of the mechanisms involved in metastasis formation is, therefore, a major public health issue. Among the proposed risk factors, chemical environment and pollution are increasingly suggested to have an effect on the signaling pathways involved in metastatic tumor cells emergence and progression. The purpose of this article is to summarize current knowledge about the role of environmental chemicals in breast cancer progression, metastasis formation and resistance to chemotherapy. Through a scoping review, we highlight the effects of a wide variety of environmental toxicants, including persistent organic pollutants and endocrine disruptors, on invasion mechanisms and metastatic processes in BC. We identified the epithelial-to-mesenchymal transition and cancer-stemness (the stem cell-like phenotype in tumors), two mechanisms suspected of playing key roles in the development of metastases and linked to chemoresistance, as potential targets of contaminants. We discuss then the recently described pro-migratory and pro-invasive Ah receptor signaling pathway and conclude that his role in BC progression is still controversial. In conclusion, although several pertinent pathways for the effects of xenobiotics have been identified, the mechanisms of actions for multiple other molecules remain to be established. The integral role of xenobiotics in the exposome in BC needs to be further explored through additional relevant epidemiological studies that can be extended to molecular mechanisms.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Poluentes Ambientais/toxicidade , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Progressão da Doença , Feminino , Humanos
13.
Ann Pathol ; 40(2): 70-77, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32046878

RESUMO

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.


Assuntos
Síndrome Hereditária de Câncer de Mama e Ovário , Proteína BRCA1/análise , Proteína BRCA1/genética , Proteína BRCA2/análise , Proteína BRCA2/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Testes Genéticos , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/tratamento farmacológico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
15.
Breast J ; 24(6): 1006-1009, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30298539

RESUMO

We compared the performance of near-infrared imaging using indocyanine green (ICG) with the radioisotope (ISO) method to detect sentinel lymph nodes (SLNs) in breast cancer, to analyze predictive factors for negative ICG identification. The study included 122 patients who underwent sentinel lymph node biopsy (SLNB) using the combined ISO and ICG technique for primary breast cancer. We assessed the putative association between pathologic/clinical variables and ICG failure to detect SLNs. The ISO identification rate was 96.7% and ICG identification 81.9%. Overweight patients or presence of macrometastasis in SLNB were associated with the risk of ICG failing to detect SLNs (P = 0.02).


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico por imagem , Linfonodo Sentinela/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Meios de Contraste , Feminino , Humanos , Verde de Indocianina , Metástase Linfática/patologia , Pessoa de Meia-Idade , Sobrepeso , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos
17.
J Gynecol Obstet Hum Reprod ; 53(1): 102707, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061495

RESUMO

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.


Assuntos
Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Eletrocirurgia/métodos , Estudos Retrospectivos , Displasia do Colo do Útero/cirurgia , Margens de Excisão
18.
J Gynecol Obstet Hum Reprod ; 53(1): 102703, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040334

RESUMO

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.


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Humanos , Feminino , Verde de Indocianina , Neoplasias da Mama/patologia , Corantes , França
19.
Int J Tryptophan Res ; 16: 11786469231185102, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719171

RESUMO

The Aryl hydrocarbon receptor (AhR) is a xenobiotic and endobiotic receptor, which regulates many cellular processes from contaminant metabolism to immunomodulation. Consequently, it is also involved in pathophysiological pathways and now represents a potential therapeutical target. In this review, we will highlight the ancestral function of the protein together with an illustration of its ligand's battery, emphasizing the different responses triggered by these high diverse molecules. Among them, several members of the kynurenine pathway (one key process of tryptophan catabolism) are AhR agonists and are subsequently involved in regulatory functions. We will finally display the interplay between Tryptophan (Trp) catabolism and dysregulation in metabolic pathways drawing hypothesis on the involvement of the AhR pathway in these cancer-related processes.

20.
J Visc Surg ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38087701

RESUMO

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.

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