Validation of hysteroscopic view in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding

STUDY OBJECTIVE: To validate hysteroscopic view with histology in cases of endometrial hyperplasia and cancer in patients with abnormal uterine bleeding (AUB)DESIGN: Retrospective study.(Canadian Task Force classification II-3).SETTING: University teaching hospitals in Rio de Janeiro and São Paulo, and private office in Rio de Janeiro.PATIENTS: Four thousand and fifty-four patients with AUB in whom hysteroscopic views were complete and the histologic result was conclusive.INTERVENTION: Four thousand and fifty-four office hysteroscopies with complete views and conclusive histologic results. The material for histologic examination was obtained through biopsy of the lesion in an outpatient unit or through the resection of the entire lesion in patients who underwent surgery. Histology was considered the gold standard and compared with the hysteroscopic view.MEASUREMENTS AND MAIN RESULTS: In the histology of the 4054 examinations, 613 (15.2%) were endometrial hyperplasia, and 105 (2.6%) were endometrial cancer. The most frequent hysteroscopic finding was endometrial polyps (31.2%). In endometrial hyperplasia, the sensitivity of the hysteroscopic view was 56.3% (95% CI 52.21-60.2%), specificity was 89.1% (95% CI 88.0%-90.1%), positive predictive value (PPV) was 48.0% (95% CI 44.3%-51.7%), negative predictive value (NPV) was 92.0% (95% Cl 90.1%-92.9%), and accuracy was 72.7% (95% CI 70.7%-74.7%). Accuracy was defined as the proportion of correct results among the hysteroscopic examinations. In endometrial cancer, the sensitivity of the hysteroscopic view was 80.0% (95% Cl 71.1%-87.2%), specificity was 99.5% (95% CI 99.2%-99.7%), PPV was 81.5% (95% Cl 72.7%-88.5%), NPV was 99.5% (95% CI 99.2%-99.7%), and accuracy was 89.8% (95% CI, 85.9%-93.6%). In the 814 patients (20.0%) in whom the hysteroscopic view was normal, there were no false negatives for endometrial cancer; however, there were 37 (4.5%) false negatives for endometrial hyperplasia. In the histologic cases of endometrial cancer, 101 (96.2%) hysteroscopic views were compatible with cancer or hyperplasia (80.0% and 16.2%, respectively). Ninety-seven out of 103 hysteroscopic views with cancer findings (94.2%) had histologic diagnosis of cancer or hyperplasia (81.5% and 12.6%, respectively).CONCLUSION: It seems that even in face of good validity of hysteroscopic view for endometrial hyperplasia and cancer, histologic study is mandatory in the presence of any lesion as the hysteroscopic view cannot completely replace the histologic study in patients with AUB. (C) 2006 AAGL. All rights reserved.

Usefulness of Clinical, Ultrasonographic, Hysteroscopic, and Immunohistochemical Parameters in Differentiating Endometrial Polyps From Endometrial Cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação histeroscópica e imuno-histoquímica dos pólipos endometriais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pólipos endometriais e seu risco de malignização: aspectos epidemiológicos, clínicos e imunoistoquímicos

Endometrial polyps are neoformations that result from focal hyperplasia of the endometrial basal layer associated with hormonal hyperstimulation. Their pathogenesis is still unclear, and there is no consensus on their natural history, actual relevance as pathologic entities, and relationship with endometrial neoplasia. Endometrial polyps are the most frequent indication of surgical hysteroscopy, but their optimal management remains controversial. Therefore, an overview of this condition may help choosing the most adequate treatment strategies.

Claudina-3 e Claudina- 4, potenciais marcadores de agressividade no carcinoma endometrial Tipo I

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Considerations about ocular neoplasia of dogs and cats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A curva de regressão da gonadotrofina coriônica humana é útil no diagnóstico precoce da neoplasia trofoblástica gestacional pós-molar?

OBJETIVO: avaliar a utilidade da curva de regressão normal da gonadotrofina coriônica humana (hCG) no diagnóstico precoce de neoplasia trofoblástica gestacional pós-molar (NTG). MÉTODOS: estudo longitudinal, incluindo 105 pacientes com mola hidatiforme completa (MHC) acompanhadas no Centro de Doenças Trofoblásticas de Botucatu, entre 1998 e 2005. Os títulos da hCG sérica foram mensurados quinzenalmente em todas as pacientes. Curvas individuais de regressão da hCG das 105 pacientes foram estabelecidas. A comparação entre a curva de regressão normal estabelecida em nosso serviço com as curvas individuais da hCG foi usada no rastreamento e diagnóstico (platô/ascensão) de NTG. O número de semanas pós-esvaziamento quando a hCG excedeu o limite normal foi comparado com o número semanas em que a hCG apresentou platô/ascensão. RESULTADOS: das 105 pacientes com MHC, 80 apresentaram remissão espontânea (RE) e 25 desenvolveram NTG. Das 80 pacientes com RE, 7 (8,7%) apresentaram, inicialmente, dosagem da hCG acima do normal, mas, no devido tempo, alcançaram a remissão. Todas as 25 pacientes com NTG apresentaram desvio da curva normal da hCG em 3,8±2,5 semanas e mostraram platô ou ascensão em 8,4±2,9 semanas (p<0,001). CONCLUSÕES: a curva de regressão normal da hCG pós-molar pode ser útil para diagnóstico de NTG.

Best site for embryo transfer: the upper or lower half of endometrial cavity?

BACKGROUND: the objective of the present study was to determine the importance of the site of embryo transfer (upper or lower half endometrial cavity) on implantation and clinical pregnancy rates. METHODS: A total of 400 transfers guided by ultrasound were randomly assigned to two groups according to the distance between the uterine fundus and the catheter tip at the time of embryo placement. Group I (n=200) consisted of transfers corresponding to a distance of <50% of the endometrial cavity length (ECL), i.e. transfer in upper half of the cavity; and group II (n=200) consisted of transfers corresponding to a distance of greater than or equal to50%, of the ECL, i.e. transfer in lower half of cavity. The Student's t-test, Mann-Whitney test and Fisher's exact test were used where appropriate. RESULTS: the general characteristics of the study population and the main transfer cycle characteristics had an equal distribution (P>0.05) between groups I and II. No significant difference in implantation or pregnancy rates was observed between groups I and II. CONCLUSION: the implantation or pregnancy rates were similar whether the embryos were deposited in the upper or lower half of the endometrial cavity.

TRAIL-R3-related apoptosis: Epigenetic and expression analyses in women with ovarian neoplasia

Objective. To assess the expression of TRAIL-R3 and the methylation of a CpG island within the TRAIL-R3 promoter both in cystadenoma tumors and primary and metastatic epithelial ovarian carcinoma (EOC).Methods. RNA was obtained from women with normal ovarian (NO) tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and EOC (n = 16) using Trizol (R). Quantitative PCR (gRT-PCR) was performed to quantify the relative levels of TRAIL-R3. The methylation frequency of the CpG island in the TRAIL-R3 promoter was assessed using the methylation-specific PCR (MSP) assay after DNA bisulfite conversion. The differences between the groups were evaluated using the chi-square, Student's t, ANOVA, Mann-Whitney U, Wilcoxon or Kruskal-Wallis tests as indicated. The survival rates were calculated using the Kaplan-Meier method.Results. Cystadenoma and metastatic EOC tumors expressed significantly more TRAIL-R3 mRNA than primary EOC tumors. Methylation of the TRAIL-R3 promoter was absent in NO tissues, while hemimethylation of the TRAIL-R3 promoter was frequently found in the neoplasia samples with 45.4% of the cystadenoma tumors, 8.3% of the primary EOC samples and 11.1% of the metastatic EOC samples showing at least partial methylation (p = 0.018). Neither the expression of TRAIL-R3 nor alterations in the methylation profile were associated to cumulative progression-free survival or the overall survival in EOC patients.Conclusions. Primary EOC is associated to a lower TRAIL-R3 expression, which leads to a better understanding of the complex disease and highlighting potential therapeutic targets. Promoter DNA methylation was not related to this finding, suggesting the presence of other mechanisms to transcriptional control. (C) 2012 Elsevier B.V. All rights reserved.

Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia

The inflammatory response is an active process in cervical cancer and may act in the progression and/or regression of the lesion. At the site of inflammation, macrophages and neutrophils are present as well as cytokines such as TNF-alpha and IFN-gamma. This study aims to evaluate the inflammatory response levels in women with cervical intraepithelial lesions (CIN) and with squamous cell carcinoma (SCC) of the cervix. Serum samples obtained from women without evidence of disease (n = 30), with CIN (n = 30) and with SCC of the cervix (n = 30) were analyzed for the activities of N-acetylglucosaminidase (NAG) and myeloperoxidase (MPO) by enzymatic assay and the serum levels of TNF-alpha and IFN-gamma by ELISA assay. The activities of NAG and MPO and the level of TNF-alpha were higher in women with CIN compared to the women with SCC. The levels of IFN-gamma were lower in the group of women with CIN compared to the group with SCC. There was not a significant association between the degree of the CIN and the staging of the SCC of the cervix and the degree of inflammation as assessed by the levels of inflammatory markers. The inflammatory response was inversely correlated with the progression of the carcinogenic process. In the three groups, the control group, women with CIN and women with invasive SCC, there was no association between the degree of preinvasive lesions and staging of the SCC of the cervix. (C) 2011 Elsevier Masson SAS. All rights reserved.

Maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia in Brazilian women

Objective. To evaluate maternal and perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia (GTN) in Brazilian patients.Methods. This study included 252 subsequent pregnancies after chemotherapy for GTN treated between 1960-2005. Correlations of maternal and perinatal outcomes with chemotherapy regimen (single or multiagent) and the time interval between chemotherapy completion and first subsequent pregnancy were investigated.Results. There was a significant increase in adverse maternal outcomes in women who conceived <6 months than 6-12 months (76.2% and 19.6%; p<0.0001; OR=13.12; CI 95%=3.87-44.40) and >12 months (76.2% and 21.7%; P<0.0001; OR=11.56; CI 95%=3.98-33.55) after chemotherapy. Spontaneous abortion frequency was higher <6 months (71.4%) than 6-12 months (17.6%; p<0.0001: OR=11.66; CI 95%=3.55-38.22) and >12 months (9.4%; p<0.0001: OR=23.97: CI 95%=8.21-69.91) after chemotherapy. There was no difference in adverse perinatal outcomes (stillbirth, fetal malformation, and preterm birth) related to the interval after chemotherapy and Subsequent pregnancy. The overall occurrence of adverse maternal and perinatal outcomes did not significantly differ between patients on single or multiagent regimens.Conclusion. Adverse maternal outcomes and spontaneous abortion were more frequent among patients who conceived within 6 months of chemotherapy completion. In these cases, careful prenatal monitoring and hCG level measurement 6 weeks after the completion of any new pregnancy are recommended. (C) 2008 Elsevier B.V. All rights reserved.

Influence of Hydatidiform Mole Follow-Up Setting on Postmolar Gestational Trophoblastic Neoplasia Outcomes A Cohort Study

OBJECTIVE: To assess the influence of hydatidiform mole (HM) management setting (reference center versus other institutions) on gestational trophoblastic neoplasia (GTN) outcomes. METHODS: This cohort study included 270 HM patients attending Botucatu Trophoblastic Diseases Center (BTDC, São Paulo State University, Brazil) between January 1.990 and December 2009 (204 undergoing evacuation and entire postmolar follow-up at BTDC and 66 from other institutions [OIs]). GTN characteristics and outcomes were analyzed and compared according to HM management setting. The confounding variables assessed included age, gravidity, parity, number of abortions and HM type (complete or partial). Postmolar GTN outcomes were compared using Mann-Whitney's test, chi(2) test or Fisher's exact test.RESULTS: Postmolar GTN occurred in 34 (34/204= 16.7%) BTDC patients and in 27 (27/66=40.9%) of those initially treated in other institutions. BTDC patients showed lower metastasis rate (5.8% vs. 48%, p = 0.003) and lower median FIGO (2002) score (2.00 0.00, 3.001 vs. 4.00 [2.00, 7.00], p = 0.003]. Multiagent chemotherapy to treat postmolar GTN was required in 2 BTDC cases (5.9%) and in 8 OI cases (29.6%) (p = 0.017). Median time interval between molar evacuation and chemotherapy onset was shorter among BTDC patients (7.0 [6.0, 10.0] vs. 10.0[7.0, 16.0], p = 0.040). CONCLUSION: BTDC patients showed GTN characteristics indicative of better prognosis. This underscores the importance of GTD specialist centers. (J Reprod Med 2012;57:305-309)

Gestational Trophoblastic Neoplasia Following Molar Ectopic Pregnancy A Case Report

BACKGROUND: Ectopic molar pregnancy is a gestational trophoblastic disease (GTD) of rare occurrence and therefore not always remembered as a diagnostic possibility.CASE: We describe a case of molar ectopic pregnancy in a primiparous woman who developed gestational trophoblastic neoplasia and required chemotherapy to achieve remission.CONCLUSION This case stresses the important role of histopathologic examination in establishing a diagnosis of ectopic molar pregnancy. Moreover, close follow-up of human chorionic gonadotropin levels is required when a GTD is suspected. (J Reprod Med 2008;53:579-582)

Proteínas de fase aguda em cadelas com neoplasia mamária

As proteínas de fase aguda (PFA) apresentam concentrações séricas alteradas mediante processos infecciosos, inflamatórios e neoplásicos. Objetivou-se com este trabalho avaliar as variações séricas das PFA em cadelas portadoras de neoplasia mamária, comparando com a avaliação histológica e leucograma. As PFA foram avaliadas em 45 cadelas com tumor de mama, distribuídas nos grupos neoplasia benigna (n=13), maligna não ulcerada (n=24) e maligna ulcerada (n=8). O grupo controle foi composto por 20 cadelas saudáveis. Foram realizados o teste de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio (SDS-PAGE) para identificar as PFA (albumina, ceruloplasmina, transferrina, haptoglobina Hp, α-1 antitripsina e α-1 glicoproteina ácida) e o teste ultrassensível para proteína C reativa (PCR). As pacientes com neoplasia mamária maligna ulcerada apresentaram elevações sérica para PCR e Hp e redução da albumina (P<0,05, One-Way ANOVA e Teste de Dunn). Nessas pacientes, foi observada correlação positiva entre o leucograma inflamatório e o aumento das PFA (P=0,002, Teste de Fisher) e não foram observadas correlações entre as PFA e os subtipos histológicos. Conclui-se que avaliações conjuntas da PCR, Hp e albumina podem ser utilizadas como ferramenta de auxílio diagnóstico e prognóstico em cadelas com neoplasia mamária.