Endometrioid carcinomas with sex cord-like formations and hyalinization: spontaneous pregnancy after conservative treatment.

Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus, or corded and hyalinized endometrioid adenocarcinoma (CHEC), is a rare morphological variant of endometrioid carcinoma, for which there is limited literature and few cases reports. Most researchers tend to consider CHEC as a low-grade cancer with a favorable prognosis. Full-staging surgery is the primary choice for this disease, and no case of CHEC has been previously reported to be treated conservatively. Here, we present the following case to explore the possibility of fertility-preserving treatment for young women with CHEC. A 23-year-old nulliparous patient diagnosed with presumed stage IA CHEC received fertility-sparing treatment at the Obstetrics and Gynecology Hospital of Fudan University and got a complete response (CR) after 10 months of conservative treatment. The patient subsequently became pregnant spontaneously, successfully conceived, and gave birth to a healthy male neonate without any sign of recurrence during 37 months follow-up after CR. The patient's postpartum follow-up is continuing. Presently, CHEC is not included in the fertility-sparing field of any available guidelines. This case indicates that fertility-sparing treatment may be an option for highly selected patients with CHEC. Continuous follow-up remains mandatory to observe long-term outcomes.

Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia: A prospective, open-label, randomized controlled phase II study.

OBJECTIVE: To compare the effects 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). METHODS: This was a single-center phase II study with an open-label, randomized, controlled trial conducted between July 2017 and June 2020 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. A total of 180 patients (18-45 years) with primary AEH were randomly assigned (1:1:1) to the MA (N = 60), LNG-IUS (N = 60), or MA + LNG-IUS (N = 60) groups, in which the patients received MA (160 mg orally daily), LNG-IUS, or MA + LNG-IUS (MA 160 mg orally daily plus LNG-IUS), respectively. 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, and recurrence and pregnancy rates. All analyses were conducted in a modified intention to treat (ITT) population who underwent randomization and in whom treatment was initiated. RESULTS: The Kaplan-Meier estimate of 16-week CR rates (with 95% confidence interval) were 19.2% (9.0-29.4%) in the MA group, 35.0% (22.8-47.2%) in the LNG-IUS group, and 29.4% (17.2-41.6%) in the MA + LNG-IUS groups. Side effects such as weight gain, increased nocturnal urine, night sweat, insomnia and edema face seemed to occur less frequently in LNG-IUS group compared with MA group. No difference was found among groups regarding second endpoints. CONCLUSIONS: LNG-IUS or LNG-IUS plus MA did not show significant therapeutic benefit compared with MA alone. Further studies including sufficient sample-size are needed to validate these findings due to the underpowered design of this trial. FUNDING: 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), Shanghai sailing program (Grant No. 19YF1404200), and Shen Kang clinical project (SHDC22021219). Trial registrationClinicalTrials.govNCT03241888. https://www. CLINICALTRIALS: gov/ct2/show/NCT03241888?term=NCT03241888&draw=2&rank=1.

Hypertensive disorders of pregnancy and severe acute respiratory syndrome coronavirus-2 infection.

OBJECTIVES: We aimed to determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with an increased risk of hypertensive disorders of pregnancy (HDP). METHODS: A multicenter retrospective cohort study of all pregnant patients who had SARS-CoV-2 testing and delivered in a large health system between March 2020 and March 2021. Cases were stratified into two groups: patients who tested positive for SARS-CoV-2 during pregnancy vs. patients who tested negative. The primary outcome of HDP, defined as a composite of gestational hypertension, preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP Syndrome), and eclampsia by standard criteria, was compared between the two groups. Statistical analysis included multivariable logistic regression to adjust for potential confounders such as maternal demographics and comorbidities. Patient ZIP codes were linked to neighborhood-level data from the US Census Bureau's American Community Survey. RESULTS: Of the 22,438 patients included, 1,653 (7.4%) tested positive for SARS-CoV-2 infection. Baseline demographics such as age, body mass index, race, ethnicity, insurance type, neighborhood-built environmental and socioeconomic status, nulliparity, and pregestational diabetes differed significantly between the two groups. SARS-CoV- 2 infection in pregnancy was not associated with an increased risk of HDP compared to those without infection (14.9 vs. 14.8%; aOR 1.06 95% CI 0.90-1.24). CONCLUSIONS: In this large cohort that included a universally-tested population with several socioeconomic indicators, SARS-CoV-2 infection in pregnancy was not associated with an increased risk of HDP.

Socioeconomic disparities in fertility treatments and associated likelihood of livebirth following in vitro fertilization.

OBJECTIVE: To determine whether neighborhood-level socioeconomic characteristics are associated with the likelihood of livebirth (LB) following in vitro fertilization (IVF). Specifically, we evaluated neighborhood-level household income, unemployment rate, and educational attainment. DESIGN: A retrospective cross-sectional study was conducted for patients undergoing autologous IVF cycles. SETTING: Large academic health system. INTERVENTIONS: For each patient, ZIP code of residence was used as a proxy for neighborhood. Neighborhood characteristics were compared between patients with and without LB. Generalized estimating model was used to adjust the association between SES factors and likelihood of a live birth with respect to relevant clinical factors. RESULTS: A total of 4942 autologous IVF cycles from 2768 patients were included: 1717 (62.0%) had at least one associated LB. Patients who achieved LB from IVF were younger, had higher anti-Mullerian hormone (AMH) levels, lower body mass index (BMI), and differed by ethnic background, primary language, and neighborhood socioeconomic characteristics. In a multivariable model, language, age, AMH, and BMI were associated with a live birth from IVF. None of the neighborhood-level socioeconomic variables were associated with the total number of IVF cycles or cycles required to achieve first LB. CONCLUSION: Patients living in neighborhoods with lower annual household income have lower odds of livebirth after IVF compared to those living in more affluent areas, despite undergoing the same number of IVF stimulation cycles.

Efficacy of sentinel lymph node mapping in endometrial cancer with low- or high-intermediate risk.

BACKGROUND AND OBJECTIVES: This study was aimed to evaluate the efficacy of sentinel lymph node (SLN) mapping using indocyanine green (ICG) in Chinese women with endometrial cancer (EC). METHODS: Consecutive EC patients undergoing SLN mapping at Obstetrics and Gynecology Hospital of Fudan University were retrospectively reviewed. Overall and bilateral SLN detection rates and SLN locations were presented. Sensitivity, negative predictive value (NPV), and agreement rate were calculated and were compared between patients with low-intermediate (LIR) or high-intermediate risk (HIR). RESULTS: There were 454 patients screened, with SLN mapping with ICG performed in 428 patients and systematic lymphadenectomy performed in 159 patients. Overall and bilateral SLN detection rates were 96.50% and 82.71%, respectively. The sensitivity of SLN mapping was 80.00%, and the NPV was 97.76%. SLNs were most commonly located in obturator and external iliac regions. Efficacy of SLN mapping was higher in LIR patients than in HIR patients, with sensitivities of 100.00% and 75.00% (p > 0.05), NPVs of 100.00% and 90.00% (p = 0.002), and agreement rates of 100.00% and 92.31% (p = 0.007), respectively. CONCLUSION: SLN mapping with ICG had acceptable diagnostic efficacy in Chinese women with EC, but may cause more missed diagnoses in patients with HIR due to relatively low NPV and agreement rate.

Effect of Lockdown Period of COVID-19 Pandemic on Maternal Weight Gain, Gestational Diabetes, and Newborn Birth Weight.

OBJECTIVE: This study aimed to determine whether the lockdown period of the initial novel coronavirus disease 2019 (COVID-19) surge in New York affected gestational weight gain (GWG), newborn birth weight (BW), and the frequency of gestational diabetes mellitus (GDM). Maternal and newborn outcomes during the first wave of the pandemic were compared with those during the same timeframe in the previous 2 years. STUDY DESIGN: Retrospective cross-sectional study of all live singleton term deliveries from April 1 to July 31 between 2018 and 2020 at seven hospitals within a large academic health system in New York. Patients were excluded for missing data on: BW, GWG, prepregnancy body mass index, and gestational age at delivery. We compared GWG, GDM, and BW during the pandemic period (April-July 2020) with the same months in 2018 and 2019 (prepandemic) to account for seasonality. Linear regression was used to model the continuous outcomes of GWG and BW. Logistic regression was used to model the binary outcome of GDM. RESULTS: A total of 20,548 patients were included in the study: 6,672 delivered during the pandemic period and 13,876 delivered during the prepandemic period. On regression analysis, after adjustment for study epoch and patient characteristics, the pandemic period was associated with lower GWG (ß = -0.46, 95% confidence interval [CI]: -0.87 to -0.05), more GDM (adjusted odds ratio [aOR] = 1.24, 95% CI: 1.10-1.39), and no change in newborn BW (ß = 0.03, 95% CI: -11.7 to 11.8) compared with the referent period. The largest increases in GDM between the two study epochs were noted in patients who identified as Hispanic (8.6 vs. 6.0%; p < 0.005) and multiracial/other (11.8 vs. 7.0%; p < 0.001). CONCLUSION: The lockdown period of the pandemic was associated with a decrease in GWG and increase in GDM. Not all groups were affected equally. Hispanic and multiracial patients experienced a larger percentage change in GDM compared with non-Hispanic white patients. KEY POINTS: · The COVID-19 lockdown was associated with decreased GWG and increased GDM.. · No change in newborn BW was seen during the lockdown.. · Overall, the lockdown did not have a large clinical effect on these pregnancy outcomes..

Clinical implications of morular metaplasia in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial carcinoma patients.

OBJECTIVE: Morular metaplasia (MM) is a benign epithelial metaplasia that sometimes appears in atypical endometrial hyperplasia (AEH) and endometrioid endometrial carcinoma (EEC). However, the clinical implications of MM for fertility-preserving treatment in AEH and EEC patients are unclear. This study investigated the clinical features and impact of MM on the efficacy of fertility-preserving treatment. METHODS: We retrospectively studied 427 AEH and EEC patients who received fertility-preserving treatment. Clinical features, treatment efficacy, and onco-fertility results were compared between patients with and without MM. RESULTS: MM appeared in 147 of 427 (34.4%) patients. Among them, 49 (33.3%) had MM only before treatment (BEF group), 32 (21.8%) had sustained MM before and during treatment (SUS group), and 66 (44.9%) had MM only during treatment (DUR group). The BEF group had a higher 12-month CR rate (98.0% vs 85.7%, p = 0.017) and shorter therapeutic duration to achieve CR (4.0 vs 5.7 months, p = 0.013) than the non-MM group had. In comparison with the non-MM group, the SUS and DUR groups had a lower CR rate after 7 months of treatment (SUS vs non-MM, 37.5% vs 61.1%, p = 0.010; DUR vs non-MM 33.3% vs. 61.1%, p < 0.001), and a longer median therapeutic duration to achieve CR (SUS vs non-MM, 7.6 vs. 4.0 months, p = 0.037; DUR vs non-MM, 7.9 vs. 4.0 months, p < 0.001). CONCLUSION: Appearance of MM only before treatment was positively correlated with outcome of fertility-preserving treatment, while sustained MM or appearance of MM only during treatment implied poorer outcome of fertility-preserving treatment in AEH and EEC patients.

The efficiency of a combined injection technique for sentinel lymph node mapping in intermediate-high-risk endometrial cancer.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) mapping was considered for treating endometrial cancer (EC) which was apparent confined to the uterus. Nevertheless, intermediate-high-risk EC patients have super high risk to undergo isolated para-aortic lymph node metastases comparing with low-risk patients. Therefore, this investigation aimed to compare the efficacy of two SLN methods in detecting para-aortic lymph node metastases. METHODS: According to SLN mapping injection methods, intermediate-high-risk EC patients who received both SLN mapping and systematic lymphadenectomy were divided into the combined group (fundal and cervical injections) and the cervical group (cervical injection only). RESULTS: The para-aortic SLN detection rate in the combined group (40.4%) was higher than that in the cervical group (4.4%) with p < 0.001. While the differences concerning the sensitivity, false-negative rate, and negative predictive value between the two groups were not significant. The survival outcomes of patients were comparable between the two groups. CONCLUSION: Our data showcased that the combined (fundal and cervical) injection had a higher detection rate of para-aortic SLNs than cervical injection only. The efficiency of SLN mapping and the survival outcomes were not significantly different between the two groups. Further investigations are warranted to assess the value of combined injection regarding SLN technique.

Preterm birth among women with and without severe acute respiratory syndrome coronavirus 2 infection.

INTRODUCTION: Studies directly comparing preterm birth rates in women with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Our objective was to determine whether preterm birth was affected by SARS-CoV-2 infection within a large integrated health system in New York with a universal testing protocol. MATERIAL AND METHODS: This retrospective cohort study evaluated data from seven hospitals in New York City and Long Island between March 2020 and June 2021, incorporating both the first and second waves of the coronavirus disease 2019 (COVID-19) pandemic in the USA. All patients with live singleton gestations who had SARS-CoV-2 polymerase chain reaction (PCR) testing at delivery were included. Deliveries before 20 weeks of gestation were excluded. The rate of preterm birth (before 37 weeks) was compared between patients with positive and negative SARS-CoV-2 test results. This analysis was performed separately for resolved prenatal infections and infections at delivery, with the latter group subdivided by symptom status. Multiple logistic regression analysis was used to examine the association between SARS-CoV-2 infection and preterm birth, adjusting for maternal age, race-ethnicity, parity, history of preterm birth, body mass index, marital status, insurance type, medical co-morbidities, month of delivery, and wave of pandemic. RESULTS: A total of 31 550 patients were included and 2473 (7.8%) had laboratory-confirmed infection. Patients with symptomatic COVID-19 at delivery were more likely to deliver preterm (19.0%; adjusted odds ratio 2.76, 95% CI 1.92-3.88) compared with women with asymptomatic infection (8.8%) or without infection (7.1%). Among preterm births associated with symptomatic infection, 72.5% were medically indicated compared with 44.1% among women without infection (p < 0.001). Risk of preterm birth in patients with resolved prenatal infection was unchanged when compared with women without infection. Among women with infection at delivery, preterm birth occurred more frequently during the second wave compared with the first wave (13.6% vs. 8.7%, respectively; p < 0.006). However, this was not significant on multiple regression analysis after adjusting for other explanatory variables. CONCLUSIONS: Pregnant women with symptomatic COVID-19 are more than twice as likely to have a preterm delivery than patients without infection. Asymptomatic infection and resolved prenatal infection are not associated with increased risk.

Conservative management of grade 2 stage IA endometrial carcinoma and literature review.

PURPOSE: To explore the clinical outcomes of megestrol acetate alone or plus metformin in young women with grade 2 stage IA endometrial carcinoma who ask for preserved fertility. METHODS: Patients with stage IA grade 2 endometrial carcinoma who asked for fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between 2015 and 2017 were enrolled and retrospectively reviewed. RESULTS: Four patients were included and treated with oral megestrol acetate (160 mg per day), while metformin (500 mg, thrice daily) was added for patients with metabolic syndrome. Regular hysteroscopic examination was performed every 3 months during the conservative treatment. Overall, 75% (3/4) of the patients had a complete response, one relapsed and achieved a complete response after changing the therapy plan, and one patient had an indication of myometrial invasion during fertility-sparing treatment and chose to remove uterus. CONCLUSIONS: Fertility-sparing treatment for stage IA grade 2 endometrial carcinoma patients is worth exploration. Megestrol acetate with or without metformin combined with hysteroscopic lesion ablation may be an effective therapy.

Evaluation of anemia, malnutrition, mineral, and bone disorder for maintenance hemodialysis patients based on bioelectrical impedance vector analysis (BIVA).

BACKGROUND: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined. METHODS: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed. RESULTS: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes. CONCLUSIONS: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.

Effect of Chorionicity on Umbilical Cord Blood Acid-Base Analysis of the Second Twin.

Our objective was to determine whether chorionicity affects umbilical cord blood acid-base parameters of the second twin. This was a retrospective cohort of twin pregnancies delivered at ≥23 weeks of gestation at a tertiary hospital from 2010 to 2016. Patients were included if arterial and venous umbilical cord gas results were available for both newborns and chorionicity was confirmed histologically. Exclusion criteria included intrauterine fetal demise of either twin prior to labor, major fetal anomalies, monoamnionicity, uncertain chronicity and twin-to-twin transfusion syndrome. The primary outcome evaluated was the umbilical artery (UA) pH of the second twin. A total of 593 dichorionic (DC) and 86 monochorionic (MC) twin pregnancies were included. No difference in UA pH was observed between MC and DC twins. Among vaginal deliveries (n = 97), the UA pH of the first twin was higher than the second twin (7.26 vs. 7.24; p = .01). Twin-to-twin delivery interval (TTDI) ≥20 min was associated with a higher UA pH in the first twin compared to the second twin (7.25 vs. 7.16, respectively; p = .006). Multivariable logistic regression was used to predict arterial pH < 7.20 for the second twin; the most predictive factors were arterial pH < 7.20 for the first twin, chronic hypertension and prolonged TTDI. Chorionicity was not associated with any acid-base parameter of umbilical cord blood in either the first or second twin. No differences in neonatal outcomes were observed based on chorionicity or birth order. Populations with a lower cesarean delivery rate may yield different findings.

Clinical Implications of SARS-CoV-2 Infection in the Viable Preterm Period.

OBJECTIVE: This study aimed to determine the rate of preterm birth (PTB) during hospitalization among women diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 23 and 37 weeks of gestation and whether this rate differs by gestational age at diagnosis of infection. STUDY DESIGN: Retrospective, cross-sectional study of all women diagnosed with SARS-CoV-2 infection between 23 and 37 weeks of gestation within a large integrated health system from March 13 to April 24, 2020. Cases with severe fetal structural malformations detected prior to infection were excluded. Women were stratified into two groups based on gestational age at diagnosis: early preterm (230/7 to 336/7 weeks) versus late preterm (34 to 366/7 weeks). We compared the rate of PTB during hospitalization with infection between the two groups. Statistical analysis included use of Wilcoxon rank sum and Fisher exact tests, as well as a multivariable logistic regression. Statistical significance was defined as a p-value <0.05. RESULTS: Of the 65 patients included, 36 (53.7%) were diagnosed in the early preterm period and 29 (46.3%) were diagnosed in the late preterm period. Baseline demographics were similar between groups. The rate of PTB during hospitalization with infection was significantly lower among women diagnosed in the early preterm period compared with late preterm (7/36 [19.4%] vs. 18/29 [62%], p-value = 0.001). Of the 25 patients who delivered during hospitalization with infection, the majority were indicated deliveries (64%, 16/25). There were no deliveries <33 weeks of gestation for worsening coronavirus disease 2019 and severity of disease did not alter the likelihood of delivery during hospitalization with SARS-CoV-2 infection (adjusted odds ratio [aOR]: 0.64; 95% confidence interval [CI]: 0.24-1.59). Increased maternal age was associated with a lower likelihood of delivery during hospitalization with SARS-CoV-2 infection (aOR: 0.77; 95% CI: 0.58-0.96), while later gestational age at diagnosis of infection was associated with a higher likelihood of delivery during hospitalization (aOR: 2.9; 95% CI: 1.67-8.09). CONCLUSION: The likelihood of PTB during hospitalization with SARS-CoV-2 infection is significantly lower among women diagnosed in the early preterm period compared with late preterm. Most women with SARS-CoV-2 infection in the early preterm period recovered and were discharged home. The majority of PTB were indicated and not due to spontaneous preterm labor. KEY POINTS: · Preterm delivery is less likely among women diagnosed in the early preterm compared with late preterm.. · Most women infected in the early preterm period recovered and were discharged home undelivered.. · The majority of preterm birth were indicated and not due to spontaneous preterm labor..

Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer.

OBJECTIVE: This study aimed to evaluate the efficacy of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young patients with endometrial atypical hyperplasia (EAH) and early stage endometrial cancer (EEC) who wished to preserve their fertility. METHODS: Patients with EAH (n = 120) or well-differentiated EEC (n = 40, FIGO stage IA, without myometrial invasion) were retrospectively included. All patients received constant oral progestin combined with hysteroscopic evaluation every 3 months until achieving complete response (CR). The location, number and size of each suspected lesion or cluster were detailly recorded during the hysteroscopy. RESULTS: The median age was 32.0 year-old (range, 22-47 year-old). Totally 148 patients (97.4%) achieved CR while 3 EAH and 1 EEC patients presented with disease progression, and 8 patients were still in treatment. The mean treatment duration for achieving CR was 6.7 ±â€¯0.3 months (range, 1-18 months). After adjusting for patient age, body mass index (BMI), history of pregnancy and type of conservative therapies, lesion size ≤2 cm (OR, 0.701; 95% CI, 0.496-0.991; P = 0.045) was significantly correlated with shorter treatment time to achieve CR. Among 60 patients attempted to conceive after achieving CR, 45.0% (15/60) had been pregnant, 25.0% (15/60) delivered live birth, 13.3% (8/60) are still in pregnancy, while 6.7% experienced spontaneous abortion. CONCLUSION: Comprehensive hysteroscopic evaluation and lesion resection plus progestin therapy seem to be an effective and safe fertility sparing therapy for patients with EAH or EEC. Endometrial lesion size ≤2 cm correlated with a shorter treatment period to achieve CR.

Five cases of uterine perivascular epithelioid cell tumors (PEComas) and review of literature.

OBJECTIVES: Perivascular epithelioid cell tumor (PEComa) is a rare condition and the recognition of this condition is limited. Here we report five cases of uterine PEComa to add to the limited understanding of this rare condition. METHODS: Five cases from Obstetrics and Gynecology Hospital of Fudan University were diagnosed as uterine PEComas. We collected the patients' clinical and pathological data as well as their outcomes. RESULTS: All the five cases were diagnosed post-operationally. Fertility-sparing surgery was done for the first case and had a mass resection only. She delivered a healthy boy through the cesarean section in November 2016 and neither recurrence nor metastasis was found for 71 months. Hysterectomy was done for the other four cases. Adjuvant chemotherapy was also given for case 2 and case 4. Case 2 had combined endometrial cancer, which could be associated with tuberous sclerosis complex (TSC). She was followed up for 22 months and neither recurrence nor metastasis was detected. Neither recurrence nor metastasis was found in case 3 for 33 months. However, the patient in case 4 died of multiple dissemination and multiple organs failures, 10 months after the second surgery. The patient in case 5 had the hysterectomy and left adnexal resection and in this case we had no data about her long-term outcomes. CONCLUSION: It is still challenging to detect and diagnose uterine PEComa clinically and no consensus or guidelines have been established regarding the treatment of this condition. More case studies are needed to enlighten the underlying mechanism and help optimize the therapies for this condition.

TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation.

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation.

miR-339-5p inhibits migration and invasion in ovarian cancer cell lines by targeting NACC1 and BCL6.

This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression.

ATM may be a protective factor in endometrial carcinogenesis with the progesterone pathway.

The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.

Modulation of aryl hydrocarbon receptor (AHR)-dependent signaling by peroxisome proliferator-activated receptor ß/δ (PPARß/δ) in keratinocytes.

Whether peroxisome proliferator-activated receptor ß/δ (PPARß/δ) reduces skin tumorigenesis by altering aryl hydrocarbon receptor (AHR)-dependent activities was examined. Polycyclic aromatic hydrocarbons (PAH) increased expression of cytochrome P4501A1 (CYP1A1), CYP1B1 and phase II xenobiotic metabolizing enzymes in wild-type skin and keratinocytes. Surprisingly, this effect was not found in Pparß/δ-null skin and keratinocytes. Pparß/δ-null keratinocytes exhibited decreased AHR occupancy and histone acetylation on the Cyp1a1 promoter in response to a PAH compared with wild-type keratinocytes. Bisulfite sequencing of the Cyp1a1 promoter and studies using a DNA methylation inhibitor suggest that PPARß/δ promotes demethylation of the Cyp1a1 promoter. Experiments with human HaCaT keratinocytes stably expressing shRNA against PPARß/δ also support this conclusion. Consistent with the lower AHR-dependent activities in Pparß/δ-null mice compared with wild-type mice, 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis was inhibited in Pparß/δ-null mice compared with wild-type. Results from these studies demonstrate that PPARß/δ is required to mediate complete carcinogenesis by DMBA. The mechanisms underlying this PPARß/δ-dependent reduction of AHR signaling by PAH are not due to alterations in the expression of AHR auxiliary proteins, ligand binding or AHR nuclear translocation between genotypes, but are likely influenced by PPARß/δ-dependent demethylation of AHR target gene promoters including Cyp1a1 that reduces AHR accessibility as shown by reduced promoter occupancy. This PPARß/δ/AHR crosstalk is unique to keratinocytes and conserved between mice and humans.

Hyperinsulinemia is associated with endometrial hyperplasia and disordered proliferative endometrium: a prospective cross-sectional study.

OBJECTIVE: To explore the relationship between metabolic abnormalities and DPE (disordered proliferative endometrium), EH (endometrial hyperplasia) and type I EC (endometrial cancer). METHODS: We conducted a prospective cross-sectional study that lasted from September 2011 to September 2012 at the Obstetrics and Gynecology Hospital of Fudan University. 314 cases were enrolled, including 56 cases of DPE, 194 cases of EH and 25 cases of type I EC. 39 healthy female cases were collected as a control group. General information was collected, and blood tests, including blood lipids, OGTT (75-g oral glucose tolerance test) and insulin release tests were examined. Statistical analysis was performed using SPSS 19.0 (Chicago, USA), and 0.05 was chosen as the significance test level. RESULTS: The median (inter-quartile) age of the 314 study subjects was 44 (12) years, with the ages ranging from 21 to 75 years. Elevated insulin level was correlated with DPE, EH without/with atypia and EC. The risk increased when HOMA-IR (homeostasis model assessment-insulin resistance)≥ 2.95 (the lower limit of the top quartile of HOMA-IR distribution in non-diabetic patients); the OR (odds ratio) for DPE was 9.973 (95% CI (coefficient interval): 2.038-48.789, P=0.005), that for EH without atypia was 8.481 (95% CI:1.860-38.672, P=0.006), that for EH with atypia was 18.716 (95% CI: 3.091-113.335, P=0.001) and that for type I EC was 45.199 (95% CI: 5.886-347.065, P<0.001). Opposite trends were observed for the QUICKI (Quantitative Insulin Sensitivity Check Index). CONCLUSIONS: Hyperinsulinemia is associated with DPE and EH without/with atypia, not only with type I EC, and it might be a key factor that initiates and promotes endometrial hyperplastic lesions.