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.

Adding autogenic drainage to chest physiotherapy after upper abdominal surgery: effect on blood gases and pulmonary complications prevention. Randomized controlled trial

ABSTRACT BACKGROUND: Hypoxemia and pulmonary complications are common after upper abdominal surgery (UAS). OBJECTIVE: To examine whether inclusion of autogenic drainage (AD) in chest physiotherapy after UAS confers additional benefits in improving blood gases and reducing postoperative pulmonary complications (PPCs). DESIGN AND SETTING: Randomized controlled study conducted at Kasr Al-Ainy teaching hospital, Egypt. METHODS: A randomized controlled trial was conducted on 48 subjects undergoing elective UAS with high risk of developing PPCs. The study group received AD plus routine chest physiotherapy (deep diaphragmatic breathing, localized breathing and splinted coughing) and the control group received routine chest physiotherapy only. The outcomes included arterial blood gases measured at the first and seventh postoperative days, incidence of PPCs within the first seven days and length of hospital stay. RESULTS: Baseline characteristics were similar between groups. In the AD group, SaO2, PaO2, PaCO2 and HCO3 significantly improved (P < 0.05) while in the physiotherapy group, only SaO2 and PaO2 significantly improved (P < 0.05). Nonetheless, significant differences in post-treatment SaO2 and PaO2 between the groups were observed. The overall incidence of PPCs was 16.66% (12.5% in the AD group and 20.8% in the physiotherapy group) (absolute risk reduction -8.3%; 95% confidence interval, CI, -13.5 to 29.6%), with no significant difference between the groups. The AD group had a significantly shorter hospital stay (P = 0.0001). CONCLUSION: Adding AD to routine chest physiotherapy after UAS provided a favorable blood gas outcome and reduced the length of hospital stay. It tended to reduce the incidence of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04446520.

Adding autogenic drainage to chest physiotherapy after upper abdominal surgery: effect on blood gases and pulmonary complications prevention. Randomized controlled trial.

BACKGROUND: Hypoxemia and pulmonary complications are common after upper abdominal surgery (UAS). OBJECTIVE: To examine whether inclusion of autogenic drainage (AD) in chest physiotherapy after UAS confers additional benefits in improving blood gases and reducing postoperative pulmonary complications (PPCs). DESIGN AND SETTING: Randomized controlled study conducted at Kasr Al-Ainy teaching hospital, Egypt. METHODS: A randomized controlled trial was conducted on 48 subjects undergoing elective UAS with high risk of developing PPCs. The study group received AD plus routine chest physiotherapy (deep diaphragmatic breathing, localized breathing and splinted coughing) and the control group received routine chest physiotherapy only. The outcomes included arterial blood gases measured at the first and seventh postoperative days, incidence of PPCs within the first seven days and length of hospital stay. RESULTS: Baseline characteristics were similar between groups. In the AD group, SaO2, PaO2, PaCO2 and HCO3 significantly improved (P < 0.05) while in the physiotherapy group, only SaO2 and PaO2 significantly improved (P < 0.05). Nonetheless, significant differences in post-treatment SaO2 and PaO2 between the groups were observed. The overall incidence of PPCs was 16.66% (12.5% in the AD group and 20.8% in the physiotherapy group) (absolute risk reduction -8.3%; 95% confidence interval, CI, -13.5 to 29.6%), with no significant difference between the groups. The AD group had a significantly shorter hospital stay (P = 0.0001). CONCLUSION: Adding AD to routine chest physiotherapy after UAS provided a favorable blood gas outcome and reduced the length of hospital stay. It tended to reduce the incidence of PPCs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04446520.

Clinical implications of CTNNA1 germline mutations in asymptomatic carriers.

In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner. Life-changing prophylactic total gastrectomy should therefore also be considered in CTNNA1 mutation carriers.