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1.
Int J Clin Oncol ; 26(2): 417-428, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33433752

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic radical hysterectomy (LRH) for cervical cancer, in terms of morbidity and short-term oncologic outcome following LRH's introduction into Japan. METHODS: We conducted a retrospective analysis of patients with early-stage cervical cancer (FIGO staging IA2, IB1, and IIA1) who underwent LRH from Dec 2014 to Dec 2016. We assessed the morbidity, overall survival (OS) and recurrence-free survival (RFS), and prognostic factors for RFS. RESULTS: A total of 251 patients were included from 22 facilities across Japan. There were 8 cases of stage IA2 cervical cancer, 226 of IB1, and 17 of IIA1. The median operating time was 343 min and the median blood loss was 190 ml. Two patients (0.8%) had a postoperative complication with a Clavien-Dindo classification of grade 3 or higher. After a median follow-up time of 15.6 months, the 2-year RFS was 87.4%, and the 2-year OS was 97.8%. When the 2-year RFS rate was compared with whether the patient pathologically had tumors of less than 2 cm, versus 2 cm or more, the RFS was 95.8% and 80.4%, respectively. Multivariate analysis found that tumor size and the route of lymph node removal were independent prognostic factors for recurrence. CONCLUSION: When LRH was first introduced into Japan, we found that the route of lymph node removal was an independent prognostic factor for recurrence in addition to large tumors (≥ 2 cm). Our results suggest that prognosis may be secured by paying attention to the lymph node removal route.


Assuntos
Histerectomia , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Japão/epidemiologia , Laparoscopia , Excisão de Linfonodo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
2.
Int J Gynecol Cancer ; 27(8): 1666-1674, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28786875

RESUMO

OBJECTIVE: This study aims to clarify the incidence of Aurora kinase A (Aurora-A) protein expression and its correlation with clinical parameters in ovarian clear cell carcinoma (OCCC) tumor tissues. In addition, we assessed the efficacy of ENMD-2076, a novel selective Aurora-A inhibitor, in combination with chemotherapeutic agents for the treatment of OCCC. METHODS/MATERIALS: Aurora-A protein expression was determined by immunohistochemical staining of OCCC specimens from 56 patients to evaluate its correlation with clinical outcomes in OCCC. In the in vitro study, 6 OCCC cell lines were exposed to ENMD-2076 in combination with cisplatin, SN38, doxorubicin, or paclitaxel, and cell proliferation, cell cycle distribution, and apoptosis were assessed. RESULTS: The 5-year survival rates of International Federation of Gynecology and Obstetrics stages IC3 to IV patients with intermediate or strong Aurora-A expression were significantly lower than those of patients with negative or weak Aurora-A expression. Increased Aurora-A expression was associated with significantly worse overall survival of International Federation of Gynecology and Obstetrics stages IC3 to IV patients (21% vs 77%). Multivariate analysis revealed that Aurora-A expression was an independent prognostic factor for stages IC3 to IV OCCC patients. Furthermore, synergistic effects were observed with ENMD-2076 in combination with cisplatin or SN-38 in 4 of the 6 tested cell lines. ENMD-2076 dramatically enhanced apoptosis and cell cycle arrest at the G2/M phase induced by cisplatin. CONCLUSIONS: Aurora-A is a promising biomarker that is predictive of patient outcomes and a potential target for OCCC. The results suggested that chemotherapy, including ENMD-2076 in combination with cisplatin, is a potential treatment modality for patients with OCCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Aurora Quinase A/antagonistas & inibidores , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Pirazóis/farmacologia , Pirimidinas/farmacologia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/enzimologia , Adulto , Idoso , Apoptose/efeitos dos fármacos , Aurora Quinase A/biossíntese , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/biossíntese , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Irinotecano , Antígeno Ki-67/biossíntese , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Pessoa de Meia-Idade , Neoplasias Ovarianas/enzimologia , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Análise Serial de Tecidos
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