ABSTRACT Background The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. Methods EMPap incorporated the methylation status of BHLHE22 and CDO1 , along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. Results EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). Conclusions This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.
Objective: To evaluate the risk of lymph node metastasis and figure out necessity of lymphadenectomy in grade 3 endometroid endometrial cancer (EEC) patients. Methods: From 2009 to 2019, 3751 endometrial cancer (EC) patients were diagnosed at Gynecology Hospital of Fudan University, 1235 EEC patients were enrolled in multivariable analysis. 381 patients had survival analysis attributed to sufficient follow-up information. Kaplan-Meier curve and logrank test were used to analyze the survival rate. Results: Among 1235 EEC patients, multivariate analysis showed lymph-vascular invasion (LVSI), adnexal involvement (AI), cervical stroma involvement (CSI) were independent risk factors of lymph node metastasis (LNM) in grade 3 (G3) cohort (OR=3.45, 5.83, 8.93; 95% CI 1.12-10.64, 1.52-22.35, 2.85-28.00 respectively). LNM rates increased from 3.3% to 75% for EEC G3 cohort with the increase of risk factors from one to three. There were no differences between G3 and grade 1&2 (G1&2) in overall survival or progression free survival. Similarly, no survival advantage was found for EEC G3 patients at early stage with different plans of adjuvant treatment. Conclusion: When EEC G3 patients combine with one or more risk factors including LVSI, AI and CSI, lymphadenectomy is recommended. For those with only one factor of G3, it is recommended to evaluate the status of lymph nodes by considering other methods such as sentinel lymph node biopsy technology to avoid overtreatment. Survival analysis showed no difference in EEC G3 cohort compared with G1&2. Also, different plans of adjuvant treatment had no impact on overall survival for EEC G3 patients.
Objective To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH). Design Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020. Setting Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China Population A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60). Methods Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. Main outcomes and measures The primary endpoint was the complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were the CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate. Results LNG-IUS group yielded a higher 16-week CR rate than MA group (P=0.049; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00-6.00). However, MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). Meanwhile, less side-effects were found in LNG-IUS group compared with the other two groups. No significant difference was seen in recurrence rates and pregnancy rates among all three groups. Conclusions LNG-IUS might be considered as the first-line choice of fertility-sparing treatment in AEH patients with proper size of uterine cavity. LNG-IUS combined with MA might not provide better treatment effect than MA or LNG-IUS alone.
To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH).
Methodology
Design
Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020.
Setting
Shanghai OBGYN Hospital of Fudan University, China
Population
A total of 132 patients (18–45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60).
Methods
Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS). Main outcomes and measures The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate.
Results
LNG-IUS group yielded higher 16-week CR rate than MA group (P=0.048; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00–6.00). MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). LNG-IUS group achieved less weight gain, nocturnal urine, night sweats, insomnia, or edema face compared with the other two groups. Recurrence rates and pregnancy rates showed no difference among the three groups.
Conclusion
Our data support the usage of LNG-IUS as first line choice for fertility sparing treatment in AEH patients with proper uterine cavity size. LNG-IUS combined with MA did not provide better treatment effect than either LNG-IUS alone or MA alone. This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616) and sponsored by Shanghai sailing program (Grant No.19YF1404200).
I In nt tr ro od du uc ct ti io on n: : Pre-eclampsia (PE) is the most serious syndrome of human pregnancy and it is potentially life-threatening for both mother and fetus.The aim of the study was to identify the role of high temperature requirement A1 (HtrA1) in pre-eclampsia.M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : One hundred consecutive pregnancies complicated by PE and 100 normal controls were included in our study.The changes in serum HtrA1 and fetal growth restriction were recorded.The placentae after delivery was also obtained for laboratory analyses.R Re es su ul lt ts s: : High temperature requirement A1 expressed positively in all placenta tissues, but showed higher expression from control, PE with AGA (pre-eclamptic pregnancies with appropriate-for-gestational-age newborns) to PE with fetal growth restriction (FGR) groups.Early-onset PE happened more frequently while in PE with AGA, late-onset PE was more common.Additionally, we found that only during ~28-32 gestational weeks, sera HtrA1 level of PE with AGA and PE with FGR was increased significantly compared with the control group (p < 0.05).In contrast, there was no significant difference between groups in other gestational ages in the third trimester (p > 0.05).C Co on nc cl lu us si io on ns s: : HtrA1 could potentially affect trophoblast migration and invasion during placentation, resulting in the shallow invasion noted in pre-eclampsia.HtrA1 may play an important role in the etiology and severity of PE and FGR.But the actual mechanism still needs deep research.
Abstract Background Metabolic syndrome (MetS), a worldwide public health problem, affects human health and quality of life in a dramatic manner. A growing evidence base suggests that MetS is strongly associated with levels of systemic immune inflammation. The present study aimed to investigate the possible relationship between the systemic immune-inflammation index (SII), a novel inflammatory marker, and MetS to provide data support for effective MetS prevention by reducing the systemic inflammatory response. Methods We included adult participants with complete SII and MetS information from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). MetS was defined as using the criteria developed by the Adult Treatment Program III of the National Cholesterol Education Program. The formula for SII was as follows: SII = platelet counts × neutrophil counts/ lymphocyte counts. Weighted linear regression was used to assess differences in variables across SII quartile groups after the SII score was divided into 4 quartiles. The independent interaction between SII and MetS was investigated using weighted multivariate logistic regression analysis and subgroup analysis, and the relationship between SII levels and 5 particular MetS items was further explored in depth. Results A total of 12,402 participants, 3,489 of whom were diagnosed with MetS, were included in this study. After correcting for covariates, the results of a logistic regression of multistage weighted complex sampling data revealed that participants with higher SII scores had a higher chance of developing MetS (odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.14–1.55) and that SII levels could be used as an independent risk factor to predict that likelihood of MetS onset. In the Q1–Q4 SII quartile group, the risk of developing MetS was 1.33 times higher in the Q4 group, which had the highest level of systemic immune inflammation than in the Q1 group. After adjusting for all confounding factors, SII scores were found to have a negative correlation with high-density lipoprotein cholesterol (OR = 1.29; 95% CI, 0.99–1.67, P = 0.056) and a significant positive correlation with waist circumference (OR = 2.17; 95% CI, 1.65–2.87, P < 0.001) and blood pressure (BP) (OR = 1.65; 95% CI, 1.20–2.27, P = 0.003). Gender, age, and smoking status were shown to alter the positive association between SII and MetS in subgroup analyses and interaction tests ( p for interaction < 0.05). Additionally, we demonstrated a nonlinear correlation between SII and MetS. The findings of the restricted cubic spline indicated that there was an inverted U-shaped association between SII and MetS. Conclusions Our findings imply that increased SII levels are related to MetS, and SII may be a simple and cost-effective method to identify individuals with MetS. Therefore, protective measures such as early investigation and anti-inflammatory interventions are necessary to reduce the overall incidence of MetS.
To explore the role of laparoscopic sentinel lymph node(SLN) detection with carbon nanoparticles tracer in cervical carcinoma.Totally 21 patients with confirmed early cervical cancer were enrolled in this study.Before laparoscopic extended hysterectomy and pelvic lymphadenoetomy(and para-aortic lymphadenoectomy) , they were injected with carbon nanoparticles suspension injection tracer from cervical neck before surgery. The black-staining lymph nodes were cut as SLN under the laparoscope for routine pathological examination.Of these 21 patients, at least one SLN was successfully detected in 20 patients(95.24%) , and a total of 158 SLNs were detected.The conventional pathology results suggested that 5 patients(23.81%) had positive lymph nodes(n=16, including 14 in 4 patients) . The new approach showed a sensitivity of 80.0%(4/5) , accuracy of 100.0%(20/20) , and negative predictive value of 100.0%(16/16) for SLN detection.Laparoscopic SLN detection with carbon nanoparticles tracer is a relative safe and sensitive method for in cervical carcinoma.
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