RESUMEN
OBJECTIVE: The pathological mechanisms of gestational trophoblastic disease have not yet been clearly determined. It is thought that oxidative damage contributes to the process. The aim of this study was to determine the levels of coenzyme Q10 (CoQ 10), DNA damage, and lipid peroxidation in patients with hydatidiform mole. MATERIALS AND METHODS: The authors studied the levels of CoQ10, 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) by high-performance liquid chromatography (HPLC), and the activity of glutathione peroxidase (GPX) by spectrophotometric method in blood obtained from patients with a complete hydatidiform mole (n=29), healthy pregnant women (n=29), and healthy non-pregnant women (n=29). RESULTS: The 8-OHdG/dG ratio (2.8148 ± 0.81592) and MDA (10.8341 ± 4.64875 µmol) were significantly higher in patients with complete hydatidiform mole, while the ubiquinol-10/ubiquinone-10 ratio (0.2107 ± 0.15675) and GPX activity (43.4606 ± 18.31694 mU/mI) were lower (p < 0.001). CONCLUSION: The authors suggest that both mitochondrial oxidative and oxidative DNA damage play important roles in the pathogenesis of complete hydatidiform mole. Therefore supplementation of CoQ10 prevents recurrent gestational trophoblastic disease.
Asunto(s)
Mola Hidatiforme/metabolismo , Ubiquinona/análogos & derivados , Neoplasias Uterinas/metabolismo , Vitaminas/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Daño del ADN , Desoxiguanosina/análogos & derivados , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Mola Hidatiforme/patología , Peroxidación de Lípido , Malondialdehído/metabolismo , Mitocondrias/patología , Oxidación-Reducción , Embarazo , Ubiquinona/metabolismo , Neoplasias Uterinas/patología , Adulto JovenRESUMEN
OBJECTIVE: To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6months after uterine evacuation. METHODS: Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016. RESULTS: At 6months from uterine evacuation, 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; p<0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p=0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p=0.60). None of the women relapsed, and no deaths occurred in either group. CONCLUSION: In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gonadotropina Coriónica/sangre , Mola Hidatiforme/tratamiento farmacológico , Neoplasias Uterinas/tratamiento farmacológico , Legrado por Aspiración , Espera Vigilante , Adolescente , Adulto , Brasil , Estudios de Casos y Controles , Quimioterapia Adyuvante , Estudios de Cohortes , Ciclofosfamida/administración & dosificación , Dactinomicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Enfermedad Trofoblástica Gestacional , Humanos , Mola Hidatiforme/sangre , Mola Hidatiforme/patología , Leucovorina/administración & dosificación , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Uterinas/sangre , Neoplasias Uterinas/patología , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: Hydatidiform moles (HMs) are abnormal pregnancies with a propensity for developing persistent disease in the form of gestational trophoblastic neoplasia (GTN), which requires chemotherapy. In previous studies, the authors demonstrated that low apoptotic activity was correlated with the progression of HM to GTN, and they hypothesized that some apoptosis-related genes may determine this progression. METHODS: The differential expression of apoptotic genes in HMs that subsequently developed into GTN was compared with the same expression in HMs that spontaneously regressed using a human apoptosis array; then, the expression was evaluated with real-time quantitative polymerase chain reaction analysis and immunohistochemistry using 54 clinical samples from patients with HMs who had follow-up data available. RESULTS: Using an apoptosis array, greater expression of Mcl-1, which is an antiapoptotic gene, was detected in HMs that subsequently developed into GTN. It was confirmed that the levels of Mcl-1 RNA expression (P = 0.017) and Mcl-1 protein expression (P < 0.001) in HMs that developed into persistent disease and required chemotherapy were significantly greater compared with the levels in HMs that regressed. Moreover, Mcl-1 immunoreactivity, which was detected predominantly in cytotrophoblasts, was correlated with the apoptotic index, as assessed with M30 cytoDeath immunohistochemistry, which is a good indicator of apoptotic events in the early-stage disease. CONCLUSIONS: The current results demonstrated that Mcl-1, as identified by a cyclic DNA array, may play a role in the pathogenesis of HMs and may have potential as a useful marker for predicting the clinical behavior of HMs.
Asunto(s)
Biomarcadores de Tumor/análisis , Regulación Neoplásica de la Expresión Génica , Mola Hidatiforme/patología , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias Uterinas/patología , Adolescente , Adulto , Secuencia de Bases , Biopsia con Aguja , Estudios de Cohortes , ADN Complementario/análisis , Progresión de la Enfermedad , Femenino , Enfermedad Trofoblástica Gestacional/genética , Enfermedad Trofoblástica Gestacional/patología , Humanos , Mola Hidatiforme/genética , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Modelos Logísticos , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Proteínas de Neoplasias/genética , Embarazo , Probabilidad , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Neoplásico/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Neoplasias Uterinas/genéticaRESUMEN
Gestational trophoblastic disease (GTD) forms a heterogeneous pool of clinically and histopathologically defined entities with different malignant potential. The clinicopathologic characteristics of 158 cases, including 110 complete hydatidiform moles (CHM), 13 invasive moles, 32 choriocarcinomas, two placental site nodules and one placental site trophoblastic tumor are reported. Of all cases, 63.9% showed spontaneous regression after D&C. 36.1% resulted in a persistent or metastatic (11.4%) disease, including 12 CHM. Lung is found to be the most common site of metastasis (61%). The median time between antecedent pregnancy and GTD was 4.4 months. 44% had an antecedent CHM, 16% a term pregnancy. The median complete remission rate was 91.2% with 5.3% recurrent disease. Three women died. Eight patients received adjuvant surgical therapy for chemoresistant foci. In general, management of GTD is interdisciplinary with an emphasis placed on individualized treatment. In most cases, exact histopathologic diagnosis of the trophoblastic lesion remains the gold standard for guiding clinical therapy. Currently, there are no reliable genetic or molecular biologic markers predicting an aggressive behavior of CHM. Thus, all lesions should be followed by serial measurements of serum-HCG. All cases of persistent GTD should be treated in specialized centers.
Asunto(s)
Neoplasias Trofoblásticas/patología , Neoplasias Uterinas/patología , Adolescente , Adulto , Factores de Edad , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Coriocarcinoma/patología , Quimioterapia Combinada , Femenino , Humanos , Mola Hidatiforme/patología , Leucovorina/uso terapéutico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Metotrexato/uso terapéutico , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Trofoblásticas/terapia , Tumor Trofoblástico Localizado en la Placenta/patología , Neoplasias Uterinas/terapiaRESUMEN
From 1963 through 1985, 181 hysterography were performed for 101 patients. The diagnostic accuracy of hysterography was 92.3%. There were no false positive findings, though a negative result may be obtained in patients whose intramural lesion does not communicate with the uterine cavity, as proved by operative findings. Three types of abnormalities were observed on the hysterogram: (1) filling defect, (2) intramural invasion of the uterine wall by the contrast medium and (3) extravasation of the contrast medium into the pelvic veins. The filling defect was usually observed in patients with (1) residual molar tissue in the uterine cavity, (2) intramural lesion and (3) intrauterine adhesions. The above three conditions can be differentiated by the characteristic shape of the filling defect. If it is used in combination with either or both of the other two procedures, ie., B-ultrasound and pelvic arteriography the accuracy of diagnosis will be further improved.