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1.
Anticancer Res ; 39(11): 5953-5962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704820

RESUMO

BACKGROUND/AIM: The presence of ascites in ovarian cancer patients is considered a negative prognostic factor. The underlying mechanisms are not clearly understood. MATERIALS AND METHODS: The amount of ascites was evaluated, preferably, using diffusion-weighted MRI at primary diagnosis in a retrospective cohort of 214 women with ovarian cancer, in an ordinal manner (amount of ascites: none, limited, moderate, abundant). In a prospective cohort comprising 45 women with ovarian cancer, IL-10 (interleukin), VEGF (vascular endothelial growth factor), TGF-ß (transforming growth factor) and CCL-2 [chemokine (C-C) motif ligand 2] were measured at diagnosis (and at interval debulking, when available). RESULTS: Gradually increasing amounts of ascites were correlated significantly, even after correction for FIGO stage, with reduced survival (p<0.0001) and stronger immunosuppression (IL10 and VEGF). Neoadjuvant chemotherapy reduced immunosuppression, which was observed as a reduction in CCL-2, IL-10 and VEGF. CONCLUSION: The amount of ascites is an independent predictor of survival and correlates with increased immunosuppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ascite/mortalidade , Imunossupressão/mortalidade , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Ascite/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
2.
J Cancer Res Clin Oncol ; 145(11): 2737-2749, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586262

RESUMO

BACKGROUND: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer. MATERIALS AND METHODS: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay). RESULTS: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity. CONCLUSION: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Proliferação de Células , Estudos de Coortes , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
3.
Gynecol Oncol ; 155(2): 374-383, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31472940

RESUMO

BACKGROUND: After The Cancer Genome Atlas (TCGA) findings, four novel prognostic groups may direct the management of endometrial cancer (EC): POLE-mutated/ultramutated (POLEmt), microsatellite-instable/hypermutated (MSI), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-mutated (p53mt). However, data about prognosis in each group are different across the studies, and definitive pooled estimates are lacking after validation series. Such data may be crucial in directing clinical study design and establishing the optimal tailored management of patients. AIM: To provide pooled estimates of hazard ratio (HR) for overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) in each prognostic group. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching 7 electronic databases, from their inception to April 2019, for studies assessing prognosis in each TCGA EC group. Both univariable and multivariable HR analysis was performed for OS, DSS and PFS in each group, using p53wt as reference group. RESULTS: Six studies with 2818 patients were included. Regarding OS, pooled HRs were 3.179 and 1.986 for p53mt group, 1.522 and 1.192 for MSI group, and 0.589 and 0.795 for POLEmt group at univariable and multivariable analyses, respectively. Regarding DSS, pooled HR were 5.052 and 2.133 for p53mt group, 1.965 and 1.068 for MSI group, and 0.552 and 0.325 for POLEmt group at univariable and multivariable analyses, respectively. Regarding PFS, pooled HR were 3.512 and 1.833 for p53mt group, 1.354 and 0.817 for MSI group, and 0.287 and 0.217 for POLEmt group at univariable and multivariable analyses, respectively. CONCLUSIONS: Prognosis of p53mt group is consistently the worst one and is further worsened by unfavorable clinicopathological factors. Prognosis of MSI group overlaps with p53wt group but is worsened by unfavorable clinicopathological factors. Prognosis of POLEmt group is the best one and does not seem to be significantly affected by clinicopathological factors.


Assuntos
Neoplasias do Endométrio/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/genética , Métodos Epidemiológicos , Feminino , Genoma Humano , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Proteína Supressora de Tumor p53/metabolismo
4.
Gynecol Oncol ; 155(2): 254-261, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31519319

RESUMO

OBJECTIVE: Neuroendocrine carcinoma of the endometrium (NECE) is a rare malignancy. We examined the natural history and outcomes of women with NECE compared to patients with poorly differentiated endometrioid endometrial cancer (EC). METHODS: The National Cancer Database (NCDB) was used to identify women with NECE and women with poorly differentiated EC from 2004 to 2015. Clinical, demographic, and treatment characteristics were compared between groups. Kaplan-Meier survival curves and multivariable Cox proportional hazard regression models were used to identify associations between tumor histology and survival. RESULTS: A total of 28,291 women with EC and 364 women with NECE were identified. Patients with NECE were more often non-white and presented with later stage disease compared to patients with EC. Women with NECE were more likely to receive adjuvant chemotherapy (60.2% vs. 29.6%), but were less likely to receive radiation (28.0% vs. 47.6%) (P < 0.001 for both). Median survival was 17 months (95% CI, 12-23) for NECE and 144 months (95% CI, 140-148) for EC. 5-year survival was 38.3% (95% CI, 32.7-43.8%) for NECE vs. 68.8% (95% CI, 68.2-69.4%) for EC. In a multivariable model, the hazard ratio for death for women with NECE compared to EC was 2.32 (95% CI, 1.88-2.88). Similar findings were noted when the analysis was limited to women with stage I (HR = 1.62; 95% CI, 1.01-2.61), and stage III (HR = 2.57; 95% CI, 1.88-3.53) neoplasms. CONCLUSIONS: NECE is a rare and aggressive uterine carcinoma. Compared to patients with poorly differentiated EC, patients with NECE present with later stage disease and have decreased survival.


Assuntos
Carcinoma Neuroendócrino/patologia , Neoplasias do Endométrio/patologia , Tumores Neuroendócrinos/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/terapia , Quimioterapia Adjuvante , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/terapia , Radioterapia Adjuvante , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
5.
Medicine (Baltimore) ; 98(33): e16855, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415417

RESUMO

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecologic tumors, with a high incidence in developed countries. Although the overall prognosis is good, some women have invasive tumors, the risk of recurrence, and death is high. The common surgical methods used in EC are total-abdominal hysterectomy (TAH), total-vaginal hysterectomy (TVH), laparoscopic-assisted vaginal hysterectomy (LAVH), and total-laparoscopic hysterectomy (TLH) including both conventional and robotically assisted. METHODS: The literature search was performed in The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, and Embase. The randomized controlled trials (RCTs) will be included. The search date is until June 2019. The risk of bias of included RCTs was assessed by 2 investigators according to the Cochrane Collaboration's tool. Network meta-analysis will be conducted by R software. RESULTS: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This network meta-analysis will provide clinical staff with current and reliable information on the best surgical approach for EC. Ethical approval is not applicable, since this is a network mate-analysis based on published articles. The protocol has been registered on PROSPERO under the number CRD42019128094.


Assuntos
Neoplasias do Endométrio/cirurgia , Histerectomia Vaginal/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Laparoscopia/métodos , Recidiva Local de Neoplasia/mortalidade , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/métodos
6.
Zhonghua Bing Li Xue Za Zhi ; 48(8): 590-595, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31422588

RESUMO

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion: BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.


Assuntos
DNA Helicases/metabolismo , Neoplasias do Endométrio , Proteínas Nucleares/metabolismo , Proteína SMARCB1/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais , China , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Imuno-Histoquímica
7.
Zhonghua Fu Chan Ke Za Zhi ; 54(7): 452-457, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31365957

RESUMO

Objective: To analyze the clinicopathological features and prognosis of patients in endometrial cancer with bone metastases. Methods: A retrospective review of medical records was performed to analyze patients with endometrial cancer who developed bone metastases at Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017, including patients with bone metastases at the diagnosis of endometrial cancer and at recurrence of endometrial cancer. The patient's clinicopathological features, bone metastasis characteristics, treatment process and prognoses were also analyzed. Results: The incidence of bone metastasis of endometrial cancer in PUMCH from 2004 to 2017 was 0.57% (14/2 458). (1) General clinical pathological features: the median age of the 7 patients with bone metastases diagnosed at the time of initial diagnosis was 50 years old, and the main pathological type was endometrioid carcinoma (n=5). The median age of the other 7 patients was 57 years old, with no significant difference comparing to the former groups (P=0.559). (2) The majority site of bone metastasis in endometrial cancer were discovered in pelvic bones, followed by the tibia. (3) Treatment: according to the staging of endometrial cancer, a comprehensive treatment based on surgery was performed, and one patient with isolated bone metastases underwent resection of bone metastasis. (4) Prognosis: nine out of the 14 patients died during the follow-up period. The median over all survival time was 25.5 months (range: 7.7-258.0 months). The median survival of population after diagnosis of bone metastases was 15.0 months (range: 3.0-51.0 months). The survival rate of endometrial cancer at 1-year after diagnosis of bone metastasis was 71.4%. The 2-year survival rate was 40.8%. (5) No independent prognostic factors affecting survival was found (P>0.05). Conclusions: The incidence of bone metastasis in endometrial cancer is less than 1%. Bone metastasis could occur at the diagnosis of endometrial cancer or recurrence of endometrial cancer. Bone metastasis suggests a poor prognosis. There is no standard follow-up and treatment protocols so that individualized treatment is needed.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma/secundário , Neoplasias do Endométrio/patologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Carcinoma/mortalidade , Carcinoma/terapia , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
BMC Public Health ; 19(1): 921, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291920

RESUMO

BACKGROUND: Endometrial cancer is the second most common cancer among female cancer survivors in the US and is increasing in incidence. Rural endometrial cancer patients experience lower survival rates but the reasons for the lower survival are not known. The aim of this study is to examine whether prognostic factors are different for rural and urban patients in a population-based cohort. METHODS: Endometrial cancer patients diagnosed 1997-2012 were identified through the Utah Cancer Registry and Utah Population Database. The address at cancer diagnosis was used to classify patients in rural or urban residences. Demographic and cancer-specific characteristics were examined as prognostic factors for both all-cause and endometrial cancer-specific mortality using Cox proportional hazards models. RESULTS: There were 2,994 endometrial cancer patients and 14.1% of these patients lived in rural areas at diagnosis. Rural endometrial cancer patients were older at cancer diagnosis and did not appear to be different in terms of obesity or overweight at cancer diagnosis. There were no differences for treatment or stage at diagnosis although rural patients had higher proportions of higher grade. Age at diagnosis, poverty, education, and histology were significant prognostic factors for all-cause death. Rural patients with more advanced stages of cancer had significantly increased risks of all-cause and endometrial cancer-specific death than urban patients. Rural endometrial cancer patients diagnosed at advanced stage had a 17-fold increase in the risk of all-cause death compared to an 8-fold increase in death for urban patients. CONCLUSIONS: Rural endometrial cancer patients in Utah were older at diagnosis, had higher grade and higher comorbidities. While urban and rural endometrial cancer patients shared many prognostic factors, the risk of mortality is greater among rural patients with advanced stage endometrial cancer. Future studies should examine where patients are receiving treatment and how that impacts their survival and how to reduce the mortality rates of high risk patients.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , População Rural/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Utah/epidemiologia
9.
Gynecol Oncol ; 154(3): 487-494, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31257010

RESUMO

OBJECTIVES: To determine which patients with locoregionally advanced endometrial cancer may benefit from pelvic external beam radiotherapy (EBRT) in addition to chemotherapy compared to chemotherapy alone. METHODS: Patients with FIGO stages III-IVA endometrial carcinoma between 2004 and 2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of pelvic EBRT, analyzed using the Kaplan-Meier method and Cox multivariable regression. RESULTS: In total, 13,270 patients were identified (62% pure endometrioid, 38% serous/clear cell or mixed histology; 22.6% stage IIIA, 4.7% stage IIIB, 71.2% stage IIIC, 1.5% stage IVA), of whom 40% received pelvic EBRT. In univariable analysis, EBRT was associated with absolute 5-year survival increases of 5% and 9% in the endometrioid and non-endometrioid cohorts, respectively (P < 0.0001). In multivariable analyses stratified by stage and histology, patients with a significant benefit from EBRT were stage IIIC (specifically IIIC2) endometrioid (adjusted hazard ratio [HR] 0.73, P = 0.01) and stages IIIB and IIIC non-endometrioid (adjusted HR 0.52, P = 0.01 and adjusted HR 0.79, P < 0.0001). The benefit of EBRT in node-positive patients persisted in those who underwent more extensive lymphadenectomy. CONCLUSIONS: Stages III-IVA endometrial cancer comprised a heterogeneous population with respect to the added benefit of radiotherapy compared to chemotherapy alone. Patients with stage IIIC2 endometrioid and stages IIIB-C non-endometrioid cancer may be most likely to benefit from pelvic EBRT.


Assuntos
Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Carcinoma Endometrioide/patologia , Quimioterapia Adjuvante , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Sistema de Registros , Estados Unidos/epidemiologia
10.
N Engl J Med ; 380(24): 2317-2326, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189035

RESUMO

BACKGROUND: Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence. METHODS: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life. RESULTS: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group. CONCLUSIONS: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia Adjuvante , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasia Residual , Prognóstico , Qualidade de Vida , Recidiva , Estatísticas não Paramétricas , Resultado do Tratamento
11.
Folia Histochem Cytobiol ; 57(2): 84-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198984

RESUMO

INTRODUCTION: WNT5A (Wnt family member 5A) belongs to the WNT family of secreted signaling glycoproteins that play essential role in developmental, physiological and pathological processes. WNT5A was shown to take part in carcinogenesis process playing both oncogenic and suppressor functions in various types of human malignancies. This study aimed to assess the expression of the WNT5A gene at the mRNA and protein levels in the specimens derived from endometrial cancer (EC) or unchanged control endometrium. The associations between the WNT5A expression levels and clinicopathological characteristics and survival of EC patients were evaluated. MATERIALS AND METHODS: Total RNA was isolated in order to assess the relative amounts of WNT5A mRNA by quantitative polymerase chain reaction (QPCR) in samples of unchanged endometrial control (n = 8) and tumor samples of EC patients (n = 28). Immunohistochemistry (IHC) was used to determine the presence of WNT5A protein in the sections of formalin-fixed, paraffin-embedded tissue specimens derived from unchanged endome-trial controls (n = 6) and EC tumors (n = 19). Significance of differences in WNT5A expression levels between the studied groups of EC patients and correlations between the WNT5A and demographic data, pathological features, hematological parameters and overall survival of the patients were evaluated by statistical analysis. RESULTS: The level of WNT5A mRNA was decreased in EC in comparison to unchanged endometrium. WNT5A expression was associated with primary tumor invasion status exhibiting reduced level of transcripts in EC that involved organs beyond the uterus when compared to the uterus-confined cancers. WNT5A immunoreactivity was visualized in the cytoplasm and nuclei of EC cells as well as in the luminal and glandular epithelial cells of unchanged endometrium. WNT5A mRNA expression levels correlated negatively with cytoplasmic, and positively with nuclear immunoreactivity of the WNT5A protein in the EC cells. In addition, the relationships between blood leucocyte count (in particular granulocytes and lymphocytes) of patients with EC and their WNT5A mRNA and protein expression levels were established. A positive correlation between the nuclear immunoexpression of WNT5A protein in the cancer cells in cell nuclei and mean platelet volume in blood was also found. CONCLUSIONS: The results of the first study of WNT5A expression at the transcript and protein levels indicate that it could be considered as a potential marker of molecular changes that take place during EC development.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , RNA Mensageiro/metabolismo , Proteína Wnt-5a/genética , Proteína Wnt-5a/metabolismo , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Regulação para Baixo , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/mortalidade , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Proteína Wnt-5a/imunologia
12.
Gynecol Oncol ; 154(1): 156-162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31060820

RESUMO

BACKGROUND: Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer. METHODS: After IRB approval, records of women with diagnosis and treatment of endometrial cancer from 1999 to 2016 were abstracted for histopathological, treatment and demographic data. Death was confirmed by query of the Social Security Death Index. Kaplan Meier survival curves and Cox regression modeling was performed with Stata version 14.0. RESULTS: Of 1732 evaluable patients, there were significant differences in age at diagnosis, histology (endometrioid versus non-endometrioid), stage, race, grade, hypertension, hyperlipidemia, diabetes, and treatment between normal weight, overweight, obese, and morbidly obese patients (p < 0.01). There was a linear association of younger age at diagnosis with increasing obesity (p < 0.01) R2 = 0.04. Younger age, endometrioid histology, lower stage, and statin use were independently associated with decreased hazard of death (p < 0.01). However, in stratified analysis of non-endometrioid histologies, patients with Stage 3 and 4 disease over the age of 65 showed a survival benefit for women associated with obesity (p = 0.02). CONCLUSIONS: Obesity is associated with younger age at diagnosis and earlier stage disease. Obesity is associated with improved disease specific survival for stage 3 and 4 non-endometrioid endometrial cancers.


Assuntos
Neoplasias do Endométrio/mortalidade , Obesidade/mortalidade , Fatores Etários , Idoso , Carcinoma Endometrioide/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Obesidade Mórbida/mortalidade , Sobrepeso/mortalidade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
13.
Int J Clin Oncol ; 24(10): 1256-1263, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31098693

RESUMO

OBJECTIVE: The selection criteria for secondary cytoreductive surgery (SCS) for recurrent endometrial cancer (EC) remain to be defined. The present study aimed to identify predictors for favorable survival after SCS for the disease. METHODS: We retrospectively reviewed the medical records of 112 patients who relapsed by 2016 among 1052 who were diagnosed with primary EC between 1985 and 2014. Characteristics associated with overall survival (OS) after SCS were identified using univariate and multivariate analyses. RESULTS: Twenty-nine of the 112 patients who relapsed underwent SCS. Complete resection was achieved in 18 (62%) patients, whose OS after SCS was significantly better than that of patients receiving incomplete resection (68 vs. 20 months; p = 0.001). Endometrioid histology and performance status (PS) 0 were significant and independent factors for a favorable OS (p = 0.005, and 0.049). The OS of patients with both factors was better than patients with one or no factors (median 75, 19 and 4 months; p = 0.001 and 0.00001). The number of predictors was associated with the rate of complete resection (p = 0.001). CONCLUSIONS: Patients with endometrioid histology and PS 0 should be offered SCS for recurrent EC. Prospective trials are warranted to verify this proposal.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Neoplasias do Endométrio/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Int J Clin Oncol ; 24(9): 1129-1136, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31069549

RESUMO

OBJECTIVE: To examine the necessity and sufficiency of different types of hysterectomy for the surgical treatment of endometrial cancer. METHODS: This was a multicenter collaborative study conducted by 11 institutions. Among patients with stage I-III endometrial cancer who underwent surgery as the initial treatment (only chemotherapy was provided if adjuvant therapy was needed) from 2001 to 2012, we retrospectively examined the type of hysterectomy, clinicopathological factors, recurrence rate over a maximum period of 5 years, and the site of recurrence. The local recurrence rate was examined by univariate and multivariate analyses. RESULTS: Among 1335 patients, 982 (73.6%) underwent simple hysterectomy (SH) and 353 (26.4%) underwent modified radical hysterectomy (mRH) and were observed for a mean duration of 51.8 months. No significant difference was observed in the rate of local recurrence between the SH and mRH groups (p = 0.928). In multivariate analysis, clinicopathological factors independently associated with localized recurrence included postmenopausal status [hazard ratio (HR) 5.036, 95% confidence interval (CI) 1.506-16.841, p = 0.009], with stages II (HR 3.337, 95% CI 1.701-6.547, p < 0.001) and III (HR 2.445, 95% CI 1.280-4.668, p = 0.007), vs stage I and histological type 2 (HR 1.610, 95% CI 0.938-2.762, p = 0.001). CONCLUSIONS: For endometrial cancer patients requiring surgery, the selection of a more extensive type of hysterectomy did not reduce the rate of local recurrence. Therefore, there is little significance in performing mRH in such cases.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento
15.
World J Surg Oncol ; 17(1): 80, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077193

RESUMO

OBJECTIVE: To investigate the predictive value of lymphovascular space invasion (LVSI) for nodal recurrence and overall survival (OS) in patients with stage I endometrioid endometrial cancer (EC) following surgical staging that included adequate lymph node sampling. METHODS: Retrospective analyses of patients undergoing surgical staging for FIGO stage I endometrioid EC between 1998 and 2015 were performed using an institutional database and the National Cancer Database (NCDB). Using the institutional database, logistic regression modeling identified predictors of nodal recurrence; Cox proportional hazards modeling was used to predict progression-free survival (PFS). Utilizing NCDB, Cox proportional hazards modeling was used to predict OS. The Kaplan-Meier method was used to estimate hazard ratios (HR). Survival curves were compared using the log-rank test. RESULTS: Among 275 institutional cases, LVSI was present in 48 (17.5%). There were 11 nodal recurrences: 18.8% (9/48) of cases with LVSI had a nodal recurrence compared to 0.88% (2/227) of those without LVSI. In multivariate analysis of institutional data, LVSI was the only significant predictor of nodal recurrence (p = 0.002). Among 28,076 NCDB cases, LVSI was present in 3766 (13.5%). In multivariate analysis of NCDB, grade 3, LVSI, and depth of invasion (all p <  0.001) were prognostic for OS after adjusting for adjuvant radiation. CONCLUSION: LVSI is an independent prognostic factor for nodal recurrence in stage I endometrial cancer with lymph node assessment. LVSI is associated with lower OS in NCDB. Given these findings, adjuvant therapy could be considered in these patients.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/mortalidade , Linfonodos/patologia , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Terapia Combinada , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
17.
Gynecol Oncol ; 154(1): 65-71, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31027900

RESUMO

BACKGROUND: According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS: Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS: Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS: The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Sistema de Registros , Risco , Resultado do Tratamento
18.
Asian Pac J Cancer Prev ; 20(4): 1185-1190, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030493

RESUMO

Objective: To determine the effects of uterine adenomyosis on endometrial cancerrecurrence rates. Methods: This retrospective cohort study reviewed all consecutive patients diagnosed with endometrial cancerwho underwent total hysterectomy-based surgical staging at Srinagarind Hospital between January, 2010 and January, 2016. The patientswere divided into two groups:a uterine adenomyosisgroup and a non-adenomyosis group. Patient demographics, type of surgery, histopathology, stage of endometrial cancer, adjuvant treatment, and survival outcomes were compared. Results: A total 350 patients were enrolled, with 132 (37.71%) in the adenomyosis group and 218 (62.29%) in the nonadenomyosis group. Deep myometrial invasion and lymphovascular space invasion (LVSI) were more commonly found among patients who had no adenomyosis compared to those with adenomyosis(52.8% vs 39.4%, P=0.02 and 53.2% vs. 38.6%, P=0.01). There were no significant differences in terms of five-year recurrence-free survival (HR=1.47; 95%CI 0.88-2.44) and five-year overall survival (HR=0.81; 95%CI 0.43-1.53) between the two comparison groups. Conclusion: Coexisting uterine adenomyosis in endometrial cancer wasassociated withdeep myometrial invasion and LVSI but did not have significant impact on survival.


Assuntos
Adenomiose/mortalidade , Neoplasias do Endométrio/mortalidade , Neoplasias Uterinas/mortalidade , Adenomiose/complicações , Adenomiose/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/complicações , Neoplasias Uterinas/terapia
19.
Med Sci Monit ; 25: 2811-2818, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30992424

RESUMO

BACKGROUND This retrospective clinical study aimed to investigate the effect of prognostic factors and adjuvant radiotherapy in patients with high-grade early-stage endometrial cancer on overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS The medical records of patients diagnosed with high-grade, early stage (I or II) endometrial adenocarcinoma who had received adjuvant radiotherapy after surgery were reviewed. RESULTS Seventy-nine patients included 39 patients (49.4%) with stage II endometrial cancer, 25 patients (31.6%) with histologic grade 3 tumors, and 47 patients (59.5%) with endometrial cancer showing lymphovascular space invasion (LVSI). There were 45 patients (57.0%) who received external pelvic radiotherapy with an average dose of 46.0 Gy (range, 11.2-50.4 Gy), and 34 patients (43.0%) received vaginal brachytherapy (VBT) with an average dose of 21.5 Gy (range, 10-36 Gy). Multivariate analysis showed that tumor stage (HR, 4.066; 95% CI, 1.227-13.467; p=0.022) and histologic grade (HR, 16.652; 95% CI, 4.430-62.589; p<0.001) were independent predictors for OS. Increased serum CA-125 levels (HR, 1.136; 95% CI, 0.995-1.653; p=0.047) and histologic grade (HR, 3.236; 95% CI, 1.107-15.156; p=0.015) were independent predictors for DFS. Adjuvant radiotherapy was not found to be significantly associated with improved OS (HR, 1.259; 95% CI, 0.518-3.058; p=0.612) or DFS (HR, 1.056; 95% CI, 0.994-1.123; p=0.078). CONCLUSIONS This retrospective study showed that in high-grade early-stage endometrial cancer treated with postoperative adjuvant radiotherapy, independent predictors for OS were tumor stage and grade. Adjuvant radiotherapy was not associated with improved OS or DFS.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Radioterapia Adjuvante/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Intervalo Livre de Doença , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Gynecol Oncol ; 153(3): 505-510, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30935714

RESUMO

OBJECTIVES: To evaluate the prognostic impact of aortic vs. pelvic lymph node (LN) metastasis among women with endometrial cancer (EC). METHODS: Using data from the SEER 18 Registries we identified 3650 women with LN positive (stage IIIC) EC. We used Kaplan-Meier curves and log-rank tests to compare mortality between women with stage IIIC1 and IIIC2 disease. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between stage III sub-stage (IIIC1 vs. IIIC2) and survival. RESULTS: Endometrioid tumors were more common among women with stage IIIC1 than IIIC2 tumors (62.5% vs. 54.3%) while, non-endometrioid histologies were more common among stage IIIC2. In the multivariable model, stage IIIC2 was associated with higher all-cause (HR = 1.44, 95% CI = 1.22-1.69) and EC-specific mortality (HR = 1.49, 95% CI = 1.25-1.77) compared with IIIC1. Women with non-endometrioid EC had poor survival, in particular, women with carcinosarcomas had higher EC-specific mortality compared to women with endometrioid EC (HR = 3.32, 95% CI = 2.71-4.07). When stratifying women according to substage, older age and non-endometrioid histology were associated with higher EC-specific mortality. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower all-cause (HR = 0.74, 95% CI = 0.63-0.88) and EC-specific (HR = 0.79, 95% CI = 0.66-0.95) mortality. CONCLUSION: Women with aortic LN positive EC are more likely to die from their disease. Older women and non-endometrioid histologies are more likely to have aortic LN involvement. Compared to women with a pelvic-only LN dissection, women with pelvic and aortic dissections had lower EC mortality.


Assuntos
Carcinoma Endometrioide/secundário , Carcinossarcoma/secundário , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Linfonodos/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Aorta , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/cirurgia , Carcinossarcoma/mortalidade , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve , Prognóstico , Modelos de Riscos Proporcionais , Programa de SEER , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
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