Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 10.644
Filtrar
1.
Zhonghua Fu Chan Ke Za Zhi ; 55(2): 112-119, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32146740

RESUMO

Objective: To investigate the surgical complications in the treatment of stage Ⅰ endometrial cancer by robotic-assisted laparoscopy, the risk degree of Clavein-Dindo complications and the main risk factors affecting the occurrence of surgical complications. Methods: A retrospective case-control study was conducted in the First Affiliated Hospital of Zhengzhou University from October 2014 to June 2019. The patients were divided into robotic-assisted laparoscopy group and traditional laparoscopy group according to the operation mode, including 131 cases in robot group and 290 cases in traditional laparoscopy group. To compare the complications during and after operation and the risk degree of complications between the two groups by Clavein-Dindo classification standard, the age, body mass index (BMI), comorbidities, past history of pelvic surgery, American Society of Anesthesiologists (ASA) grade, preoperative anemia, number of pelvic lymph node resection, number of abdominal aortic lymph node resection, the total number of lymph node resection, operation time, surgical methods (robot surgery or traditional laparoscopic surgery) and other clinicopathological data were analyzed by logistic regression analysis. Results: (1) Complications of operation: the incidence of operative complications (including intraoperative and postoperative complications) in robot group was significantly lower than that in traditional laparoscopy group [(20.6%, 27/131) vs (34.8%, 101/290); χ(2)=8.620, P=0.003)]. The incidence of intraoperative complications in robot group was lower than that in traditional laparoscopy group [1.5% (2/131) vs 6.2% (18/290); χ(2)=4.368, P=0.037]. The incidence of intraoperative vascular injury in robot group was significantly lower than that in traditional laparoscopy group [0.8% (1/131) vs 5.2% (15/290); χ(2)=4.798, P=0.022]. The incidence of postoperative complications in robot group was also lower than that in traditional laparoscopy group [19.1% (25/131) vs 28.6% (83/290); χ(2)=4.303, P=0.038], but the incidence of postoperative lymphatic leakage in robot group was higher than that in traditional laparoscopy group [10.7% (14/131) vs 5.2% (15/290); χ(2)=4.279, P=0.039]. (2) Clavein-Dindo classification: the incidence of Clavein-Dindo Ⅰ, Ⅲ, Ⅲ, Ⅳ and Ⅴ grade between two groups were respectively 3.8% (5/131) vs 11.0% (32/290), 13.7% (18/131) vs 14.5% (42/290), 3.1% (4/131) vs 8.6% (25/290), 0 (0/131) vs 0.3% (1/290), 0 (0/131) vs 0.3% (1/290), and the incidence of grade Ⅰ (χ(2)=5.684, P=0.015) and Ⅲ (χ(2)=4.361, P=0.037) complications were statistically significant. The incidence of severe complications in robot group (grade Ⅲ and above) was lower than that in traditional laparoscopy group [3.1% (4/131) vs 9.3% (27/290); χ(2)=5.179, P=0.023]. (3) Analysis of influencing factors of surgical complications: univariate analysis showed that BMI (χ(2)=15.801, P=0.000), preoperative anemia (χ(2)=14.299, P=0.000), total number of lymph node resection (χ(2)=10.425, P=0.001), surgical methods (χ(2)=8.620, P=0.003) were related to the occurrence of surgical complications of endometrial carcinoma. Multivariate analysis showed that BMI (OR=0.289, 95%CI: 0.097-0.864, P=0.026), preoperative anemia (OR=0.309, 95%CI: 0.129-0.740, P=0.008), the total number of lymph node resection (OR=0.624, 95%CI: 0.403-0.966, P=0.034) and surgical methods (OR=3.491, 95%CI: 1.030-11.840, P=0.045) were independent risk factors for surgical complications of endometrial carcinoma. Conclusions: Compared with traditional laparoscopic surgery, robot-assisted laparoscopic surgery has fewer complications and lower incidence of severe complications. BMI, preoperative anemia, the total number of lymph node resection and surgical methods are independent risk factors for the occurrence of surgical complications of stage Ⅰ endometrial cancer.


Assuntos
Neoplasias do Endométrio/cirurgia , Laparoscopia , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos de Casos e Controles , China/epidemiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
2.
Orv Hetil ; 161(10): 382-388, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32115990

RESUMO

Introduction: Recently published unfavourable results of endoscopic radical surgery for early-stage cervical cancer compared to open surgery raises the need for auditing treatment results of endoscopic staging surgery for endometrial cancer. Aim: Comparison of progression-free and overall survival (PFS and OS) between endometrial cancer patients treated with laparoscopic (LSC) and open surgical techniques. Method: Retrospective analysis was performed to compare clinicopathological and survival data of endometrial cancer patients who had either laparoscopic or open staging surgery between 2013 and 2019 at the Gynaecological Oncology Unit of the University of Debrecen, Hungary. Distribution of the most relevant prognostic factors were compared with χ2 and t-tests. Frequencies of progressive disease and disease-specific deaths were compared in the Cox-model, while progression-free and overall survival curves were compared with the Kaplan-Meier method. Results: The frequency of endometrioid, serous papillary, mixed Müllerian, adenosquamous and other histological types in the laparoscopic and open groups were similar (p = 0.3356). The frequency of grade 1, 2 and 3 tumours in the endoscopic and open groups showed significant differences (p = 0.0036). Pathological stage-distribution (IA, IB, II, IIIA, IIIB, IIIC1, IIIC2) of endoscopic cases and open cases was also statistically different (p = 0.0048). The mean number of removed lymph-nodes was higher in the open surgery group (14.3 vs. 9,3, p<0.0001). The frequency of recurrence did not show significant difference between the two groups, in contrast to the frequency of disease-specific deaths (2/120 vs. 29/345, p = 0.01; 2/120 vs. 17/345, p = 0.12). In the Cox-model, progression-free survival and overall survival showed a hazard ratio favouring laparoscopic surgery, however, the range of 95% confidence intervals showed no statistical significance (PFS LSC vs. open: HR = 0.36, 95% CI = 0.084-1.538; OS LSC vs. open: HR = 0.603, 95% CI = 0.135-2.693). Conclusion: Progression-free and overall survival of endoscopically staged endometrial cancer is not worse than those of patients staged with open surgery. Orv Hetil. 2020; 161(10): 382-388.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Histerectomia , Laparoscopia/métodos , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Hungria/epidemiologia , Excisão de Linfonodo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
3.
Anticancer Res ; 40(2): 789-794, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014921

RESUMO

BACKGROUND/AIM: To investigate tumor suppression as an indicator of malignization potential within endometrial polyps in asymptomatic postmenopausal women. MATERIALS AND METHODS: Immunohistochemical studies of the phosphatase and tensin homolog (PTEN) were performed. Cases included 52 benign postmenopausal polyps, 19 endometrioid carcinomas with coexisting benign polyps, and 12 polyps with foci of carcinoma. Controls included 31 atrophic endometria and 32 benign premenopausal polyps. PTEN was scored by quantitative methods according to staining intensity. RESULTS: The mean epithelial and stromal PTEN H-score in postmenopausal benign endometrial polyps (193.8 and 123.2, respectively) was significantly higher than that in the atrophic endometrium (135.5 and 90.2, p=0.008), and premenopausal benign endometrial polyps (100.7 and 198.7, p<0.001). Significant difference between postmenopausal endometrial polyps and endometrial carcinoma was noticed in the epithelial compartment (193.8 vs. 65.7, respectively, p<0.001). CONCLUSION: Asymptomatic benign postmenopausal polyps have a distinctively high tumor suppression compared with endometrial cancer, suggesting low malignization potential.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Pólipos/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pólipos/patologia , Pós-Menopausa , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 99(8): e19281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080141

RESUMO

BACKGROUND: The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. METHODS: The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software. RESULTS: Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26). CONCLUSION: This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.


Assuntos
DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Mutação , Proteínas de Ligação a Poli-ADP-Ribose/genética , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Linfonodos/patologia , Miométrio/patologia , Invasividade Neoplásica , Prognóstico , Intervalo Livre de Progressão
5.
J Surg Oncol ; 121(4): 599-604, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31994195

RESUMO

BACKGROUND AND OBJECTIVES: Only a few studies have reported the learning curve for sentinel lymph node (SLN) detection in gynecologic malignancies. We investigated the learning curve for SLN detection during robot-assisted laparoscopic surgery for endometrial and cervical carcinomas. METHODS: This retrospective analysis included patients with stage IA to IIA1 cervical cancer or stage I to III endometrial cancer who underwent SLN mapping using indocyanine green during robot-assisted laparoscopic surgery performed by a single surgeon. Learning curves were analyzed in consecutive cases using SLN detection rates and the cumulative sum (CUSUM) method. RESULTS: SLN mapping was achieved in 81.25% (65/80), 77.50% (62/80), and 66.25% (53/80) of the cases involving the right, left, and simultaneous bilateral pelvic areas, respectively. Learning curve analysis based on the cumulative detection rate showed initial fluctuations followed by stabilization; the time required for proficiency was discordant among the LN regions. However, the CUSUM method showed proficient mapping of the right, left, and bilateral SLNs after 27 to 28 cases. CONCLUSION: At least 27 cases were required for SLN mapping proficiency in gynecologic cancer; the learning period could influence the surgical quality. Further studies are warranted to confirm the impact of this learning curve on disease outcomes.


Assuntos
Neoplasias do Endométrio/patologia , Curva de Aprendizado , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Corantes , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Verde de Indocianina , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Robóticos , Biópsia de Linfonodo Sentinela/normas , Neoplasias do Colo do Útero/cirurgia
6.
Life Sci ; 243: 117254, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31917993

RESUMO

Uterine corpus endometrial cancer (UCEC) is one of the most common gynecological malignancies with increasing incidence and high morbidity and mortality. The currently acknowledged molecular mechanism of UCEC is still not adequate. Here, we reported that the expression of a novel long non-coding RNA (lncRNA) FRMD6-AS2 was reduced in UCEC compared to noncancerous endometrium tissues using the data from The Cancer Genome Atlas (TCGA) Project database. The gene ontology (GO) analysis on differential expressed targeted genes of FRMD6-AS2 in UCEC suggested that FRMD6-AS2 might impact with the function of actin-mediated cell movement and contraction. By over-expressing FRMD6-AS2 in UCEC cell lines, we observed that FRMD6-AS2 played a suppressive role in tumor growth, migration and invasion via activation of Hippo signaling pathway including FRMD6. Moreover, we also demonstrated that FRMD6-AS2 could interact with the 30 kb upstream beyond FRMD6 and facilitate the chromatin looping towards the promoter region of FRMD6 to enhance the expression of FRMD6. We concluded that lncRNA FRMD6-AS2 repressed UCEC, at least in part, by increasing FRMD6.


Assuntos
Proteínas do Citoesqueleto/genética , Neoplasias do Endométrio/genética , Genes Supressores de Tumor , Proteínas de Membrana/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Neoplasias do Endométrio/patologia , Feminino , Humanos , Transdução de Sinais
7.
Gynecol Oncol ; 156(1): 243-250, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31703813

RESUMO

Early endometrial cancer has an overall survival of greater than 80% (1). One of the poor prognostic factors that may be associated with the 20% who do not survive 5 years is the presence of lymphovascular space invasion (LVSI). LVSI is associated with increased nodal metastasis and decreased progression free survival (PFS) and overall survival (OS). (2-8). Therefore, unstaged, LVSI positive early endometrial cancer requires additional management with either completion of staging with lymphadenectomy or adjuvant radiation. We focus on reviewing the management of natural history and management of early endometrial cancer followed by the prognostic impact of LVSI, management options and recommendations.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Metástase Linfática , Sistema Linfático/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante
8.
Gynecol Oncol ; 156(1): 70-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739992

RESUMO

OBJECTIVES: The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND). METHODS: We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test. RESULTS: 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8). CONCLUSIONS: SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting.


Assuntos
Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Análise de Sobrevida
9.
Gynecol Oncol ; 156(1): 62-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776037

RESUMO

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Algoritmos , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adenocarcinoma de Células Claras/patologia , Idoso , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
10.
Life Sci ; 243: 116910, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610211

RESUMO

AIMS: Tomoregulin-2 (TMEFF2) is a single-pass transmembrane protein whose specific functions and mechanisms in endometrial carcinoma (EC) remain unclear. The aim of this study was to investigate the expression, prognostic role, and potential regulatory mechanisms of TMEFF2 in EC. MATERIALS AND METHODS: The expression and prognosis of TMEFF2 in EC were analyzed via bioinformatics and verified by immunohistochemistry and survival analysis. Proliferation, invasion, and migration of EC cells in vitro were assessed by cell functional assays, while epithelial-mesenchymal transition (EMT) markers and key signaling pathway proteins were evaluated by western blotting. KEY FINDINGS: The expression of TMEFF2 in EC was significantly higher than that in atypical hyperplasia and normal endometrium, the high expression of TMEFF2 was correlated with advanced stage, poor differentiation, and lymph node metastasis, and also predicted a poor prognosis of EC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMEFF2 and its related genes were enriched in the central nervous system, cell adhesion, signal transduction, and several critical signaling pathways. We also elucidated TMEFF2 networks of kinase, microRNA, and transcription factor targets. In vitro, the proliferation, invasion, and migration abilities of EC cells decreased after TMEFF2 downregulation. Downregulation of TMEFF2 reduced the activation of MAPK and PI3K signaling pathways, and inhibited EMT. SIGNIFICANCE: TMEFF2 plays an important role in the initiation, development, and malignant behavior of EC and can be a potential target for early diagnosis and treatment in EC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/genética , Prognóstico , Proteínas Quinases/metabolismo , RNA Mensageiro/genética
11.
Oncology ; 98(2): 98-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31597138

RESUMO

BACKGROUND: Endometrial cancer currently represents the most frequent gynecologic malignancy in Western countries, and the seventh most common cancer in women. For advanced-stage disease, the recurrence risk is high, and the site of the relapse is heterogeneous with localized or spread peritoneal disease. There are few therapeutic strategies, and the quality of life is poor. CASES PRESENTATION: We present 3 cases of peritoneal-spread recurrences of endometrial cancer in patients with advanced stage at diagnosis. The patients had been subjected to multiple lines of chemotherapy including re-challenging with platinum regimens, pegylated liposomal doxorubicin, and taxane, with progression of disease. These patients came to us with abdominal distension, dyspnea, elevated CA 125, and presence of ascites. After paracentesis with a single administration of intraperitoneal chemotherapy based on carboplatin, all 3 patients showed improvement in their quality of life and breathing as well as reduction of fatigue and anorexia. No complications occurred. CONCLUSION: Although only 3 cases are reported, the exceptional results and the absence of side effects observed strongly warrant future trials to investigate the role intraperitoneal chemotherapy can have both as palliative treatment of refractory ascites and as salvage therapy in advanced endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ascite/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Retratamento , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Int J Radiat Oncol Biol Phys ; 106(3): 496-502, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759077

RESUMO

PURPOSE: Variability exists in the adjuvant treatment for endometrial cancer (EC) based on surgical pathology and institutional preference. The radiosensitivity index (RSI) is a previously validated multigene expression index that estimates tumor radiosensitivity. We evaluate RSI as a genomic predictor for pelvic failure (PF) in EC patients treated with adjuvant radiation therapy (RT). METHODS AND MATERIALS: Using our institutional tissue biorepository, we identified EC patients treated between January 1999 and April 2011 with primarily endometrioid histology (n = 176; 86%) who received various adjuvant therapies. The RSI 10-gene signature was calculated for each sample using the previously published algorithm. Radiophenotype was determined using the previously identified cutpoint where RSI ≥ 0.375 denotes radioresistance (RR) and RSI < 0.375 describes radiosensitivity. RESULTS: A total of 204 patients were identified, of which 83 (41%) were treated with adjuvant RT. Median follow-up was 38.5 months. All patients underwent hysterectomy with bilateral salpingo-oophorectomy with the majority undergoing lymph node dissection (n = 181; 88%). In patients treated with radiation, RR tumors were more likely to experience PF (3-year pelvic control 84% vs 100%; P = .02) with worse PF-free survival (PFFS) (3-year PFFS 65% vs 89%; P = .04). Furthermore, in the patients who did not receive RT, there was no difference in PF (P = .87) or PFFS (P = .57) between the RR/radiosensitive tumors. On multivariable analysis, factors that continued to predict for PF included the RR phenotype (hazard ratio [HR], 12.2; P = .003), lymph node involvement (HR, 4.4; P = .02), and serosal or adnexal involvement (HR, 5.3; P = .01). CONCLUSIONS: On multivariable analysis, RSI was found to be a significant predictor of PF in patients treated with adjuvant RT. We propose using RSI to predict which patients are at higher risk for failing in the pelvis and may be candidates for treatment escalation in the adjuvant setting.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/radioterapia , Perfilação da Expressão Gênica , Recidiva Local de Neoplasia/genética , Neoplasias Pélvicas/genética , Tolerância a Radiação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Excisão de Linfonodo/estatística & dados numéricos , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Intervalo Livre de Progressão , Radioterapia Adjuvante/efeitos adversos
13.
Gynecol Oncol ; 156(1): 154-161, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759772

RESUMO

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Adulto Jovem
14.
Gynecol Oncol ; 156(1): 251-259, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31767187

RESUMO

The majority of endometrial cancers are detected early with a favourable prognosis. However, for patients with advanced disease, chemotherapy response rates and overall survival remains poor. The endometrial cancer population is typically elderly with multiple co-morbidities and aggressive cytotoxic therapy may be hazardous. Therefore, there is an urgent need to define optimal treatment strategies for advanced and recurrent disease and personalise therapy based on individual tumour and patient characteristics. Three-dimensional (3D) models that preserve the tumour microenvironment and tumour-stromal interactions are increasingly important for translational research with the advent of immunotherapy and molecularly targeted agents. 3D patient-relevant pre-clinical models in endometrial cancer include spheroids, patient-derived organoids, microfluidic systems, patient-derived xenografts and patient-derived explants. Here we present a review of available 3D modelling systems in endometrial cancers, highlighting their current use, advantages, disadvantages and applications to translational research with a focus on the power of the patient-derived explant platform.


Assuntos
Técnicas de Cultura de Células/métodos , Neoplasias do Endométrio/patologia , Animais , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Xenoenxertos , Humanos , Transplante de Neoplasias/métodos , Organoides/patologia , Esferoides Celulares/patologia , Pesquisa Médica Translacional/métodos
15.
Gynecol Oncol ; 156(1): 194-202, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757464

RESUMO

OBJECTIVES: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs). METHODS: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins. RESULTS: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment. CONCLUSIONS: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy.


Assuntos
Carcinoma Endometrioide/genética , DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adulto , Idoso , Carcinoma Endometrioide/enzimologia , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Estudos de Coortes , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/metabolismo , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Prognóstico , Estudos Prospectivos
16.
Gynecol Oncol ; 156(1): 260-261, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785862

RESUMO

OBJECTIVE: Laterally extended endopelvic resection (LEER) is regarded as a surgical salvage therapy for patients with laterally recurrent gynecologic carcinomas [1]. A prerequisite for R0 resection using this excision technique is carcinoma location remote from the sciatic foramen [1,2]. However, considering the advantages provided by laparoscopy in terms of visualization and dissection, laparoscopic LEER can potentially be used to achieve R0 resection of a laterally recurrent carcinoma at the sciatic foramen [3]. METHODS: The patient underwent an abdominal radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection due to stage II endometrial carcinoma. Almost 30 years later, a recurrent endometrial carcinoma, diagnosed by needle biopsy, was detected at the pelvic sidewall. Abdominal CT scan revealed that the recurrent tumor involved the bladder, right ureter, and rectum, and was located at the right sciatic foramen. Due to a long recurrence-free interval, resection surgery was chosen as the treatment. RESULTS: Tumor resection (LEER) and reconstructive surgery were performed laparoscopically. The operation time was 540 minutes, and blood loss volume was 350 ml, with no blood transfusion. R0 resection was achieved without any intraoperative and postoperative complications. There has been no sign of recurrence during the 6 months that have passed since this surgery. CONCLUSIONS: Total laparoscopic LEER and reconstructive surgery for a recurrent endometrial carcinoma located at the right sciatic foramen is technically feasible in experienced hands.


Assuntos
Neoplasias do Endométrio/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Reconstrutivos/métodos , Salpingo-Ooforectomia/métodos
17.
Int J Gynaecol Obstet ; 148(1): 79-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31556104

RESUMO

OBJECTIVE: To assess whether statin use by endometrial cancer patients was associated with a survival advantage. METHODS: A retrospective chart review study, by the Israeli Gynecologic Oncology Group, of consecutive endometrial cancer patients who underwent surgery in one of 11 medical centers between 2002 and 2014. Clinical and pathological reports, and measures of survival were compared between statin users and nonusers. Kaplan-Meier and Cox proportional hazard models were used to assess the effect of using statins on survival measures. RESULTS: Over a mean follow-up period of 6.2 years (range, 1-12 years) for 2017 endometrial cancer patients with complete data, 663 (32.8%) used statins prior to diagnosis and 1354 (67.1%) did not. No statistically significant differences between the groups were observed for most demographic and clinical characteristics. There was no difference between statin users and nonusers in 5-year recurrence-free survival (82% vs 83%; P=0.508), disease-specific survival (86% vs 84%; P=0.549), or overall survival (77% vs 75%; P=0.901). CONCLUSIONS: In this large cohort of patients with endometrial cancer, no significant associations were found between use of statins and endometrial cancer survival.


Assuntos
Neoplasias do Endométrio/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Israel/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
J Surg Oncol ; 121(5): 730-742, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31845348

RESUMO

BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.


Assuntos
Países em Desenvolvimento , Neoplasias do Endométrio/cirurgia , Acesso aos Serviços de Saúde , Brasil , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Continuidade da Assistência ao Paciente , Diagnóstico por Imagem , Neoplasias do Endométrio/patologia , Feminino , Preservação da Fertilidade , Humanos , Histerectomia , Excisão de Linfonodo , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Exame Físico , Encaminhamento e Consulta , Biópsia de Linfonodo Sentinela , Sociedades Médicas
19.
Anticancer Res ; 39(12): 6547-6553, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810920

RESUMO

AIM: To evaluate the frequency of loss of mediator of DNA damage checkpoint protein 1 (MDC1) protein expression in endometrial cancer (EC) and to determine whether loss of MDC1 is associated with certain clinicopathological parameters. MATERIALS AND METHODS: MDC1 expression was examined in 426 samples of EC. The nuclear immunoreactivity of the protein was defined as: negative, weak, moderate and strong. RESULTS: Loss of MDC1 expression (defined as negative nuclear staining) was found in 8.9% (38/426) of ECs and was significantly associated with the loss of MRE11 homolog, double-strand break repair nuclease, RAD50 double-strand break repair protein and nibrin complex components. In addition, loss of expression of MDC1 showed a significant correlation with any mismatch repair deficiency, with endometrioid histological subtype and low tumour grading. CONCLUSION: Based on these findings, we suggest that MDC1 loss frequently occurs in ECs with microsatellite instability. Due to deficient homologous recombination DNA repair, MDC1-negative ECs might show an increased sensitivity to poly(ADP-ribose) polymerase-inhibitory therapy.


Assuntos
Proteínas de Ciclo Celular/deficiência , Enzimas Reparadoras do DNA/deficiência , Proteínas de Ligação a DNA/deficiência , Neoplasias do Endométrio/metabolismo , Proteína Homóloga a MRE11/deficiência , Proteínas Nucleares/deficiência , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Instabilidade de Microssatélites , Estadiamento de Neoplasias , Análise de Sobrevida , Análise Serial de Tecidos
20.
BMC Med Genet ; 20(1): 202, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864301

RESUMO

BACKGROUND: The morbidity and mortality of endometrial tumors, a common type of malignant cancer in women, have increased in recent years. POLE encodes the DNA polymerase ε, which is responsible for the leading strand DNA replication. Somatic mutations of POLE have been acknowledged in numerous cancers, resulting in the accumulation of DNA errors, leading to ultra-mutated tumors. Mutations in the exonuclease domain of POLE have been reported to improve progression-free survival in endometrial cancer. However, the potential relationship and underlying mechanism between POLE mutations and the prognosis of endometrial cancer patients remains unclear. METHODS: The whole exome sequencing data, RNA sequencing data, and clinical information were obtained from the TCGA database and employed for the analyses in this study. The detailed mutational information was analyzed using whole exome sequencing data and the mutated genes were shown with OncoPlot. The survival curves and cox proportional hazards regression analysis were used to accessed patient prognosis, the association of clinical characteristics and prognosis. Differentially expressed genes were analyzed by the edgeR R/Bioconductor package, then the GSEA Pre-ranked tool was used for Gene Set Enrichment Analysis (GSEA) to estimate the function of genes. Expression values were clustered using hierarchical clustering with Euclidean distance and ward linkage by the dendextend R package. RESULTS: POLE mutational status was proven to be an independent prognostic factor for endometrial cancer patients. Patients with somatic POLE mutations presented a favorable prognosis. POLE mutations regulated glycolysis and cytokine secretion, affecting cell metabolism and immune response. Autocrine motility factor (AMF)/PGI and AMFR/gp78 exhibited higher expression levels in POLE mutant patients. The comprehensive high expressions of AMFR/gp78 and low expression of POLE were associated with the favorable prognosis of endometrial cancer patients. CONCLUSIONS: This study showed the POLE mutations a vital factor in endometrial cancer patients, leading to a higher expression of AMF/PGI and AMFR/gp78. These results suggested comprehensive consideration of the POLE mutations, expression of AMF/PGI and AMFR/gp78 may provide a more feasible and effective approach for the treatment of endometrial cancer, which might improve the prognosis.


Assuntos
DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Glucose-6-Fosfato Isomerase/metabolismo , Mutação , Proteínas de Ligação a Poli-ADP-Ribose/genética , Receptores do Fator Autócrino de Motilidade/metabolismo , Transdução de Sinais , Replicação do DNA/genética , Intervalo Livre de Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Glucose/metabolismo , Humanos , Pessoa de Meia-Idade , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA