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1.
J Surg Oncol ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496048

RESUMO

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.

2.
J Surg Oncol ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569625

RESUMO

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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34546577

RESUMO

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.

4.
Comput Math Methods Med ; 2021: 2464821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367315

RESUMO

In end-stage renal disease (ESRD), vascular calcification risk factors are essential for the survival of hemodialysis patients. To effectively assess the level of vascular calcification, the machine learning algorithm can be used to predict the vascular calcification risk in ESRD patients. As the amount of collected data is unbalanced under different risk levels, it has an influence on the classification task. So, an effective fuzzy support vector machine based on self-representation (FSVM-SR) is proposed to predict vascular calcification risk in this work. In addition, our method is also compared with other conventional machine learning methods, and the results show that our method can better complete the classification task of the vascular calcification risk.

5.
J Gynecol Oncol ; 32(4): e57, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34085795

RESUMO

OBJECTIVE: This study investigated the characteristics of progestin-insensitive endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients receiving fertility-sparing treatments and assessed the therapeutic effects of second-line fertility-preserving treatments. METHODS: Three hundred and thirty-eight patients with EEC (n=75) or AEH (n=263) receiving fertility-preserving treatment were retrospectively analyzed. 'Progestin-insensitive' was defined as meeting one of the following criteria: 1) presented with progressed disease at any time during conservative treatment, 2) remained with stable disease after 7 months of treatment, and/or 3) did not achieve complete response (CR) after 10 months of treatment. Clinical characteristics and treatment results of progestin-insensitive patients receiving second-line treatment and those of progestin-sensitive patients were compared. RESULTS: Eight-two patients (59 AEH and 23 EEC) were defined as progestin-insensitive and 256 as progestin-sensitive. In multivariate analysis, body mass index ≥28.0 kg/m² (odds ratio [OR]=1.898) and lesion size >2 cm (OR=2.077) were independent predictors of progestin-insensitive status. Compared to AEH patients, progestin-insensitive EEC patients had poorer second-line treatment responses (28-week cumulative CR rate after changing second-line treatment, 56.3% vs. 85.4%, p=0.011). No statistical difference was found in CR rate among different second-line treatments. CONCLUSION: Obesity and larger lesion size were independent risk factors associated with progestin-insensitive status. In progestin-insensitive patients receiving second-line treatment, EEC patients had lower CR rate comparing with AEH patients. Further study with larger sample size is needed to evaluate efficacy of different second-line treatments for progestin insensitive patients.

6.
Am J Obstet Gynecol MFM ; 3(4): 100349, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33757936

RESUMO

BACKGROUND: The social and physical environments in which people live affect the emergence, prevalence, and severity of both infectious and noninfectious diseases. There are limited data on how such social determinants of health, including neighborhood socioeconomic conditions, affect the risk of severe acute respiratory syndrome coronavirus 2 infection and severity of coronavirus disease 2019 during pregnancy. OBJECTIVE: Our objective was to determine how social determinants of health are associated with severe acute respiratory syndrome coronavirus 2 infection and the severity of coronavirus disease 2019 illness in hospitalized pregnant patients in New York during the global coronavirus disease 2019 pandemic. STUDY DESIGN: This cross-sectional study evaluated all pregnant patients who delivered and had polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 between March 15, 2020, and June 15, 2020, at 7 hospitals within Northwell Health, the largest academic health system in New York. During the study period, universal severe acute respiratory syndrome coronavirus 2 testing protocols were implemented at all sites. Polymerase chain reaction testing was performed using nasopharyngeal swabs. Patients were excluded if the following variables were not available: polymerase chain reaction results, race, ethnicity, or zone improvement plan (ZIP) code of residence. Clinical data were obtained from the enterprise electronic health record system. For each patient, ZIP code was used as a proxy for neighborhood. Socioeconomic characteristics were determined by linking to ZIP code data from the United States Census Bureau's American Community Survey and the Internal Revenue Service's Statistics of Income Division. Specific variables of interest included mean persons per household, median household income, percent unemployment, and percent with less than high school education. Medical records were manually reviewed for all subjects with positive polymerase chain reaction test results to correctly identify symptomatic patients and then classify those subjects using the National Institutes of Health severity of illness categories. Classification was based on the highest severity of illness throughout gestation and not necessarily at the time of presentation for delivery. RESULTS: A total of 4873 patients were included in the study. The polymerase chain reaction test positivity rate was 11% (n=544). Among this group, 359 patients (66%) were asymptomatic or presymptomatic, 115 (21%) had mild or moderate coronavirus disease 2019, and 70 (13%) had severe or critical coronavirus disease 2019. On multiple logistic regression modeling, pregnant patients who had a positive test result for severe acute respiratory syndrome coronavirus 2 were more likely to be younger or of higher parity, belong to minoritized racial and ethnic groups, have public health insurance, have limited English proficiency, and reside in low-income neighborhoods with less educational attainment. On ordinal logit regression modeling, obesity, income and education were associated with coronavirus disease 2019 severity. CONCLUSION: Social and physical determinants of health play a role in determining the risk of infection. The severity of coronavirus disease 2019 illness was not associated with race or ethnicity but was associated with maternal obesity and neighborhood level characteristics such as educational attainment and household income.


Assuntos
COVID-19 , Teste para COVID-19 , Estudos Transversais , Feminino , Humanos , New York , Gravidez , SARS-CoV-2 , Determinantes Sociais da Saúde , Estados Unidos
7.
J Obstet Gynaecol Res ; 47(3): 984-991, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33403812

RESUMO

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.


Assuntos
Neoplasias do Endométrio , Preservação da Fertilidade , Antineoplásicos Hormonais/uso terapêutico , Tratamento Conservador , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Acetato de Megestrol/uso terapêutico , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
8.
Clin Exp Nephrol ; 24(12): 1162-1176, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32779058

RESUMO

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.

10.
Am J Obstet Gynecol MFM ; 2(4): 100211, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32838277

RESUMO

Background: The impact of maternal severe acute respiratory syndrome coronavirus 2 infection on placental histopathology is not well known. Objective: To determine if any significant placental histopathologic changes occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection during pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with the infection. Study Design: A retrospective cohort study of women diagnosed as having severe acute respiratory syndrome coronavirus 2 infection who delivered at a single center from April 9, 2020 to April 27, 2020, and had placental specimens reviewed by the Department of Pathology. Women with singleton gestations and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for inclusion. Historical controls selected from a cohort of women who delivered 6 months before the study period were matched in a 1:1 fashion by weeks of gestation at delivery. Histopathologic characteristics were evaluated in each placenta, and the incidence of these findings was compared between placentas of those who received a diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and historical controls, and between placentas from patients with or without typical symptoms related to the infection. Statistical analyses included the use of Wilcoxon rank-sum test and Fisher's exact test for the comparison of categorical and continuous variables. Statistical significance was defined as a P value of <.05. Results: A total of 50 placentas after the diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection and 50 historical controls were analyzed. Among the placentas from patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection, 3 (6%) were preterm (33 3/7, 34 6/7, and 36 6/7 weeks of gestation), 16 (32%) were from patients with typical symptoms related to the infection, and 34 (68%) were from patients without typical symptoms related to the infection. All patients had received a diagnosis of severe acute respiratory syndrome coronavirus 2 infection in the third trimester. Decidual vasculopathy was not visualized in any of the placentas from patients diagnosed as having severe acute respiratory syndrome coronavirus 2 infection. There was no statistically significant difference in placental histopathologic characteristics between the groups. Severe acute respiratory syndrome coronavirus 2 test results for all neonates at 24 hours of life were negative. Conclusion: Based on the results of this study, there are no significant placental histopathologic changes that occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection in women during the third trimester of pregnancy compared with a gestational age-matched historical control group. Similar incidences of histopathologic findings were also discovered when comparing placentas from patients with severe acute respiratory syndrome coronavirus 2 infection with or without the presence of symptoms typically related to the infection.


Assuntos
COVID-19 , Placenta , Complicações Infecciosas na Gravidez , SARS-CoV-2/isolamento & purificação , Adulto , Doenças Assintomáticas , COVID-19/epidemiologia , COVID-19/patologia , Teste para COVID-19/métodos , Feminino , Idade Gestacional , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , New York/epidemiologia , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/patologia , Avaliação de Sintomas/estatística & dados numéricos
12.
Cell Rep ; 32(2): 107884, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32668240

RESUMO

Recurrent copy-number alterations, mutations, and transcript fusions of the genes encoding CDKs/cyclins are characterized in >10,000 tumors. Genomic alterations of CDKs/cyclins are dominantly driven by copy number aberrations. In contrast to cell-cycle-related CDKs/cyclins, which are globally amplified, transcriptional CDKs/cyclins recurrently lose copy numbers across cancers. Although mutations and transcript fusions are relatively rare events, CDK12 exhibits recurrent mutations in multiple cancers. Among the transcriptional CDKs, CDK7 and CDK12 show the most significant copy number loss and mutation, respectively. Their genomic alterations are correlated with increased sensitivities to DNA-damaging drugs. Inhibition of CDK7 preferentially represses the expression of genes in the DNA-damage-repair pathways and impairs the activity of homologous recombination. Low-dose CDK7 inhibitor treatment sensitizes cancer cells to PARP inhibitor-induced DNA damage and cell death. Our analysis provides genomic information for identification and prioritization of drug targets for CDKs and reveals rationales for treatment strategies.


Assuntos
Quinases Ciclina-Dependentes/genética , Genoma Humano , Mutação/genética , Neoplasias/genética , Neoplasias/terapia , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/antagonistas & inibidores , Ciclinas/metabolismo , Variações do Número de Cópias de DNA/genética , Dano ao DNA/genética , Reparo do DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fenilenodiaminas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Pirimidinas/farmacologia , Transcrição Genética/efeitos dos fármacos
13.
Am J Perinatol ; 37(11): 1077-1083, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32615621

RESUMO

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..


Assuntos
Betacoronavirus/isolamento & purificação , Coeficiente de Natalidade , Infecções por Coronavirus , Trabalho de Parto Prematuro/epidemiologia , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez , Adulto , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Estudos Transversais , Feminino , Idade Gestacional , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Idade Materna , New York/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/terapia , Cuidado Pré-Natal/métodos , SARS-CoV-2 , Fatores de Tempo
14.
Twin Res Hum Genet ; 23(3): 178-183, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248867

RESUMO

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.


Assuntos
Córion/irrigação sanguínea , Sangue Fetal/metabolismo , Transfusão Feto-Fetal/sangue , Adulto , Cesárea , Córion/metabolismo , Estudos de Coortes , Parto Obstétrico , Feminino , Transfusão Feto-Fetal/genética , Transfusão Feto-Fetal/patologia , Idade Gestacional , Humanos , Hipertensão/sangue , Hipertensão/patologia , Recém-Nascido , Gravidez , Gravidez de Gêmeos/genética , Gravidez de Gêmeos/metabolismo , Estudos Retrospectivos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Artérias Umbilicais/metabolismo
15.
Diagnostics (Basel) ; 9(4)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766630

RESUMO

BACKGROUND: Carcinosarcoma of the ovary (CSO) is a rare and aggressive variant of ovarian cancer. Due to the rare nature of the disease there is insufficient evidence to make recommendations regarding standard management and overall prognosis. METHODS: An Institutional Review Board-approved study identified all our patients with CSO between January 2011 and May 2018. Demographic and outcome measures were abstracted from the medical records and tumor board files. Cox proportional hazard models, log rank tests, and comparisons of means were used to calculate significance (p < 0.05). RESULTS: 27 women with CSO were identified. The median age at diagnosis was 65 years (range 48-91). Five women (18%) presented with early stage disease (Stage I or II) and 22 patients (82%) presented with late stage III or IV disease. Twenty patients (74%) received intravenous platinum-based combination chemotherapy. Seven patients did not receive chemotherapy during their treatment course. The median overall survival was 23 months (range 2-68 months). Overall survival was not significantly worsened by the stage of disease at diagnosis. There was no difference in survival based on the age at diagnosis, tobacco status or ethnicity (p > 0.05). CONCLUSION: This is one of the largest single institution experiences with CSO. The majority of our patients presented with advanced stage disease and received adjuvant platinum-based chemotherapy after cytoreductive surgery. The median overall survival of 23 months was not affected by the stage of the disease. The optimal management of this rare disease needs further study with collaborative, prospective multi-institutional trials.

16.
Medicine (Baltimore) ; 98(45): e17658, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702617

RESUMO

Patients with idiopathic membranous nephropathy (IMN) can be categorized into phospholipase A2 receptor (PLA2R)-associated and non-PLA2R-associated cases, according to serum PLA2R antibody status. The present study aimed to determine whether clinical features differed between these.A total of 89 patients with IMN were retrospectively recruited for the present study. Serum PLA2R-Ab levels were determined by time-resolved fluoroimmunoassay. Furthermore, the relationship between serum PLA2R antibody levels and their responses to immunosuppressants among patients with a complete follow-up period, which was defined as at least 1 year, was analyzed.Among these enrollees, 71 (80.0%) patients were positive for serum PLA2R antibody. Furthermore, patients with PLA2R-associated IMN had significantly higher age (with vs without, 54.31 ±â€Š14.03 vs 46.67 ±â€Š13.30 years old; P = .04), proteinuria (4.32 ±â€Š1.84 vs 3.29 ±â€Š1.90 g/d, P = .039), and serum albumin (25.33 ±â€Š9.60 vs 31.38 ±â€Š9.52 g/L, P = .019), but had lower serum immunoglobulin G (6.83 ±â€Š2.89 vs 8.72 ±â€Š2.95 g/L, P = .016) and erythrocyte sedimentation rate (47.31 ±â€Š32.11 vs 26.33 ±â€Š27.94, P = .013), when compared to IMN patients without PLA2R. Furthermore, IMN patients without PLA2R exhibited a better response to immunosuppressants, when compared to patients with PLA2R-associated IMN (without vs with, 66.7% vs 62.5% at 6 months and 100% vs 87.5% at 12 months), but the difference was not statistically significant.Patients with PLA2R-associated IMN had higher disease severity than IMN patients without PLA2R. Furthermore, PLA2R negative patients had a better response to immunosuppressive therapies than PLA2R-positive patients, but the difference was not statistically significant.


Assuntos
Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Receptores da Fosfolipase A2/sangue , Adulto , Idoso , Sedimentação Sanguínea , Feminino , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/metabolismo , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Gynecol Oncol ; 153(1): 55-62, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30674421

RESUMO

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.


Assuntos
Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Preservação da Fertilidade/métodos , Progestinas/administração & dosagem , Administração Oral , Adulto , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Acetato de Megestrol/administração & dosagem , Metformina/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Cancer Lett ; 442: 137-147, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420335

RESUMO

Continuous estrogen signaling is thought to be the main mechanism causing endometrial cancer (EC). Studies have demonstrated that CD163+ macrophages could promote the development of estrogen-dependent EC, but the mechanisms involved remain unclear. We found that CD163+ macrophages were the dominant macrophages in atypical endometrial hyperplasia and cancer, and their infiltration was positively associated with ERα expression. CD163+ macrophages mainly increased ERα protein levels but with little upregulatory effect on ESR1 (ERα coding gene) transcripts. The ubiquitin-editing enzyme A20, screened from the endometrial microarray obtained from mice receiving a high-fat diet and sustained estrogen-intervened, was highly expressed in endometrial lesions rich with CD163+ macrophages, and positively correlated with ERα expression. Similarly, A20 and ERα were both upregulated by CD163+ macrophages via cytokines such as IL1α, IL17A and TNFα. Mechanistically, A20 overexpression in EC cells prolonged ERα protein half-life without affecting ESR1 transcripts. A20 increased functional ERα protein levels and enhanced estrogen-driven EC cell proliferation through preventing ERα protein degradation by its deubiquitinase activity. Our study revealed that A20-mediated deubiquitination of ERα might be an important mechanism by which CD163+ macrophages sensitize EC cells to estrogen.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Macrófagos/metabolismo , Receptores de Superfície Celular/metabolismo , Microambiente Tumoral , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Animais , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Receptor alfa de Estrogênio/genética , Feminino , Células HEK293 , Meia-Vida , Humanos , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Fenótipo , Estabilidade Proteica , Transdução de Sinais/efeitos dos fármacos , Ubiquitinação
19.
Arch Gynecol Obstet ; 299(1): 185-190, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30317387

RESUMO

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.


Assuntos
Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias Uterinas/patologia , Adulto , Cesárea , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Leiomioma/complicações , Leiomioma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias de Células Epitelioides Perivasculares/mortalidade , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Gravidez , Esclerose Tuberosa/complicações , Esclerose Tuberosa/patologia , Esclerose Tuberosa/cirurgia
20.
Endocr Connect ; 7(1): 36-46, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29133384

RESUMO

Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-ß estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another's activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.

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