Clinical management of incidental findings on pelvic adnexal masses.

Due to widespread use of pelvic and transvaginal ultrasound in routine gynecological evaluation, the incidental finding of adnexal masses has led to discussions about management in asymptomatic patients regarding the risk of ovarian cancer. Transvaginal ultrasonography remains the modality of choice in the evaluation of suspicious characteristics. The combined analysis of ultrasound morphological parameters with Doppler study, serum carcinoma antigen 125 and investigation of a symptom index may improve diagnosis. Surgical approach should be considered whenever there are suspicious images, rapid growth of cysts, changes in the appearance compared to the initial evaluation or when the patient has symptoms. Future studies on genetic and molecular mechanisms may help explain the pathophysiology of ovarian cancer, improving early diagnosis and treatment.

Clinical management of incidental findings on pelvic adnexal masses / Manejo clínico dos achados incidentais de massas pélvicas anexiais

Summary Due to widespread use of pelvic and transvaginal ultrasound in routine gynecological evaluation, the incidental finding of adnexal masses has led to discussions about management in asymptomatic patients regarding the risk of ovarian cancer. Transvaginal ultrasonography remains the modality of choice in the evaluation of suspicious characteristics. The combined analysis of ultrasound morphological parameters with Doppler study, serum carcinona antigen 125 and investigation of a symptom index may improve diagnosis. Surgical approach should be considered whenever there are suspicious images, rapid growth of cysts, changes in the appearance compared to the initial evaluation or when the patient has symptoms. Future studies on genetic and molecular mechanisms may help explain the pathophysiology of ovarian cancer, improving early diagnosis and treatment.

Resumo Em virtude da ampla utilização da ultrassonografia pélvica e transvaginal na avaliação ginecológica de rotina, o achado incidental de massas anexiais tem ocasionado discussões sobre a conduta em pacientes assintomáticas frente ao risco de desenvolvimento do câncer de ovário. A ultrassonografia transvaginal continua a ser a modalidade de primeira escolha na avaliação de características suspeitas. A análise conjunta de parâmetros morfológicos ultrassonográficos com o estudo Doppler, a pesquisa de CA-125 e a investigação de índice de sintomas pode incrementar as taxas de diagnóstico. Abordagem cirúrgica deve ser considerada sempre que houver alterações em exames de imagem, quando houver crescimento rápido do cisto, mudanças em seu aspecto em relação à avaliação inicial ou quando a paciente apresentar sintomatologia. Uma compreensão melhor de mecanismos genéticos e moleculares pode auxiliar na elucidação da fisiopatologia do câncer ovariano, aprimorando seu diagnóstico e tratamento precoces.

Single CpG island methylation is not sufficient to maintain the silenced expression of CASPASE-8 apoptosis-related gene among women with epithelial ovarian cancer.

Despite impressive research efforts, the biology of epithelial ovarian cancer (EOC) remains poorly understood and alterations in the expression of CASPASE-8 contribute to a worse tumor prognosis. This study assesses the methylation of the CpG island within the CASPASE-8 promoter and CASPASE-8 gene expression both in cystadenoma tumors and in primary and metastatic EOC. DNA and RNA were obtained from women with normal ovarian tissues (n=18), ovarian serous cystadenoma tumors (n=11) and EOC (n=16) using Trizol(®). The methylation frequency of the CpG island in the CASPASE-8 promoter was assessed using the methylation-specific PCR assay after DNA bisulfite conversion. Quantitative PCR was performed to quantify the relative levels of CASPASE-8 in each sample. The differences between samples with each group were evaluated using the Mann-Whitney U and Kruskal-Wallis tests as indicated. Hemimethylation of the CASPASE-8 promoter was found in 11.8% of the normal ovary samples, 20% of the cystadenoma tumors and 20% of the metastatic EOC, while methylation of the CASPASE-8 promoter was absent in the EOC primary tissues (P=0.047). An increased CASPASE-8 expression level was observed in all tumor groups. Significant differences were observed in the CASPASE-8 expression levels when compared with all ovarian tumor groups (P=0.0278). Promoter DNA methylation did not associate with expression levels of CASPASE-8, suggesting the presence of other mechanisms in relation to gene expression control in EOC; thus providing a better understanding of this complex disease.

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors.

OBJECTIVE: This study assesses TRAIL-R2 (TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL-R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer). METHODS: RNA and DNA were obtained from women with normal ovarian tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and serous EOC (n = 16) using Trizol®. Quantitative PCR was performed to quantify the relative levels of TRAIL-R2 and BCL2. The methylation frequency of the TRAIL-R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ (2), Mann-Whitney U or Kruskal-Wallis tests, as indicated. RESULTS: We identified TRAIL-R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL-R2 promoter was frequently observed in all groups; however, there were no statistically significant associations. CONCLUSIONS: Primary EOC is associated with lower TRAIL-R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.

Effects of soy isoflavones on mammographic density and breast parenchyma in postmenopausal women: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: This study aims to evaluate the effects of soy isoflavones on breast tissue in postmenopausal women. METHODS: In this randomized, double-blind, placebo-controlled study, 80 women (aged ≥ 45 y and with amenorrhea >12 mo) with vasomotor symptoms were randomized to receive either 250 mg of standardized soy extract corresponding to isoflavone 100 mg/day (n = 40) or placebo (n = 40) for 10 months. Breasts were evaluated through mammographic density and breast parenchyma using ultrasound (US) at baseline and 10-month follow-up. Independent t test, analysis of variance, Mann-Whitney U test, and χ2 trend test were used in statistical analysis. RESULTS: Baseline clinical characteristics showed no significant differences between the isoflavone group and the placebo group, with mean (SD) age of 55.1 (6.0) and 56.2 (7.7) years, mean (SD) menopause duration of 6.6 (4.8) and 7.1 (4.2) years, and mean (SD) body mass index of 29.7 (5.0) and 28.5 (4.9) kg/m2, respectively (P > 0.05). The study was completed by 32 women on isoflavone and 34 women on placebo. The groups did not differ in mammographic density or breast parenchyma by US (P > 0.05). Within each group, the baseline and final moments did not differ in mammography or US parameters significantly (P > 0.05). CONCLUSIONS: The use of soy isoflavone extract for 10 months does not affect breast density, as assessed by mammography and US, in postmenopausal women.

Quality of life in women with vulvar cancer submitted to surgical treatment: a comparative study.

OBJECTIVES: To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment. STUDY DESIGN: Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Miller's Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Student's t-test, Chi-squared test, Mann-Whitney U-test and Spearman's rho test. RESULTS: The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p<0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 ± 4.6 years and a mean of 7.3 ± 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p=0.02). CONCLUSION: Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function.

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. Quantitative PCR (qRT-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.

Inflammatory response patterns in ICSI patients: a comparative study between chronic anovulating and normally ovulating women.

The aim of this study was to evaluate inflammatory response in chronic anovulating infertility women undergoing intracytoplasmic sperm injection. Thirteen infertile women with chronic anovulation and 23 normally ovulating women were prospectively evaluated. N-acetylglucosaminidase (NAG), myeloperoxidase (MPO), monocyte chemoattractant protein 1 (MCP-1), and C-reactive protein (CRP) concentrations were evaluated in serum and follicular fluid. Women with chronic anovulation presented higher NAG and MPO activity in follicular fluid when compared with normally ovulating women. Serum MPO activity was higher in the control group compared to the chronic anovulation group. Both serum and follicular fluid CRP concentrations were higher in women with chronic anovulation in comparison with the control group. Higher MCP-1 follicular fluid concentrations and serum levels of CRP were associated with the occurrence of ovarian hyperstimulation syndrome. Patients with chronic anovulation exhibited significantly higher follicle macrophage/neutrophil activation as well as unspecific inflammatory response by comparison with normally ovulating women.

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-α and IFN-γ. 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-α and IFN-γ by ELISA assay. The activities of NAG and MPO and the level of TNF-α were higher in women with CIN compared to the women with SCC. The levels of IFN-γ 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.

Expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen.

This study was undertaken to investigate the expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen (TAM). Postmenopausal women with endometrial polyps treated with TAM (n = 20), postmenopausal women with endometrial polyps without hormone use (n = 20), postmenopausal women with atrophic endometrium (n = 20), and postmenopausal women with endometrial adenocarcinoma (n = 20) were prospectively investigated. Tissue samples were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. The data were analyzed using the Student t test, analysis of variance, and χ2 to evaluate significant differences between the groups. The level of significance was set at P < 0.05. There was no difference in the expression of p53 between the groups (P = 0.067). The expression of Ki-67 was higher in the polyp samples from TAM-treated women compared with those from the women using no hormone (P = 0.0047) and those from the women with atrophic endometrium (P = 0.008). Samples from the women with endometrial cancer was associated with higher Ki-67 expression compared with the polyp samples from TAM-treated women (P = 0.004). The expression of CD31 was higher in the polyp samples of TAM-treated women compared with that of the samples from the women with atrophic endometrium (P < 0.001) and similar to the polyp samples from the women using no hormone (P = 0.319) and to the samples from the women with endometrial cancer (P = 0.418). The use of TAM in postmenopausal women might be associated with increased cellular proliferation in endometrial polyps without interfering angiogenesis or inactivation of tumor suppressor proteins.

Association between anthropometric indicators of body fat and metabolic risk markers in post-menopausal women.

OBJECTIVE: to evaluate anthropometric indicators of body fat and their association with metabolic risk markers in postmenopausal women. METHODS: A cross-sectional study with 80 Brazilian women (40-70 years) was carried out. Body mass index (BMI = weight/height(2)), waist circumference (WC) and waist-to-hip ratio (WHR) were obtained for anthropometric evaluation. Trunk fat mass (TFM) was measured by dual-energy X-ray absorptiometry. The following metabolic variables were evaluated: total cholesterol (TC), HDL, LDL, triglycerides (TG), as well as glycemia and insulin to determine insulin resistance (HOMA-IR). RESULTS: Overweight and obesity were observed in 81% of the women. Values of WC >88 cm were observed in 68.5% of the women. On average, TC, LDL and TG levels were above normal levels in 60, 50 and 42.5% of the women, respectively; and HDL was normal in 82.5%. IR was observed in 37.5% of the women. Positive correlations were found between anthropometric indicators and TFM (P < 0.05). WC was most correlated with TFM (r = 0.92), followed by BMI (r = 0.88) and by WHR (r = 0.48; P < 0.05). All anthropometric indicators and TFM showed significant negative correlations with HDL and significant positive correlations with HOMA-IR (P < 0.05). Only WHR was significantly associated with dysglycemia (R(2) = 12%), hypertriglyceridemia (R(2) = 17%) and decreased HDL (R(2) = 27%). WC was significantly associated with HOMA-IR (R(2) = 34%). CONCLUSION: WC and WHR are anthropometric measures that showed strong correlation with TFM and with metabolic risk markers in postmenopausal women.

[Quality of life in postmenopausal women, users and non-users of hormone therapy]. / Qualidade de vida em mulheres na pós-menopausa, usuárias e não usuárias de terapia hormonal.

PURPOSE: to evaluate the quality of life of post-menopause women, users and non-users of hormonal therapy (HT), in a Healthcare Unit in Franca, São Paulo, Brazil. METHODS: a clinical transversal study, carried out with 250 post-menopausal women, with ages from 45 to 70 years old, attended to in Healthcare Units, from September 2007 to August 2008. Participants were divided into two groups: HT users (n=70) and non-users (n=180). Women making continuous HT use for at least six months were considered as users. Sociodemographic and clinical characteristics have been evaluated. Blatt-Kupperman's menopausal index has been applied to assess climacteric symptoms, and the Women's Health Questionnaire (WHQ), to assess their quality of life. Fisher's exact test or chi2 and Mann-Whitney and Kruskal-Wallis's tests have been used for the statistical analysis. RESULTS: no significant difference has been found in the comparison of groups, concerning age, menarche, menopause, parity and body mass index. It has been seen that 67.2% of the women were married, 83.2% had attended primary school and 53.2% were housewives, with no difference between the groups. HT users reported lower frequency of climacteric symptoms (BKMI) with moderate and marked intensity, as compared to non-users (p<0.001). Even though HT users presented lower average score in cognitive deficit (p<0.001), vasomotor symptoms (p=0.04), sleeping problems (p<0.001), attractiveness (p=0.02) from the WHQ, there has been no difference in the total score, as compared to non-users. CONCLUSIONS: post-menopausal women, HT users and non-users, admitted at Healthcare Units, have not presented differences in global quality of life.

Qualidade de vida em mulheres na pós-menopausa, usuárias e não usuárias de terapia hormonal / Quality of life in postmenopausal women, users and non-users of hormone therapy

OBJETIVO: avaliar a qualidade de vida (QV) de mulheres na pós-menopausa usuárias e São Paulo. MÉTODOS: foi conduzido estudo clínico transversal, com 250 mulheres na pós-menopausa, idade entre 45 a 70 anos, atendidas em uma Unidade Básica de Saúde (UBS), de setembro de 2007 a agosto de 2008. As participantes foram divididas em dois grupos: usuárias de terapia hormonal (TH, n=70) e não usuárias (n=180). Consideraram-se como usuárias de TH aquelas que faziam uso contínuo dessa terapia há pelo menos seis meses. Foram avaliadas as características sociodemográficas e clínicas. Aplicou-se o Índice Menopausal de Blatt e Kupperman (IMBK), para avaliar a intensidade dos sintomas climatéricos, e o Questionário de Saúde da Mulher (QSM), para a avaliação da QV. A análise estatística foi realizada pelo teste do χ2 ou exato de Fisher, teste de Mann-Whitney e de Kruskal-Wallis. RESULTADOS: não foram encontradas diferenças significativas na comparação entre os grupos quanto à idade, menarca, menopausa, paridade e índice massa corpórea. Observou-se que 67,2% eram casadas, 83,2% com ensino fundamental e 53,2% se ocupavam com os trabalhos domésticos, não diferindo entre os grupos. As usuárias de TH relataram menor frequência de sintomas climatéricos (IMBK) de intensidade moderada e acentuada, comparadas a não usuárias (p<0,001). Na avaliação do QSM, verificou-se, entre as usuárias de TH, menor escore médio quanto ao déficit cognitivo (p<0,001), sintomas vasomotores (p=0,04), problemas com o sono (p<0,001) e atratividade (p=0,02), contudo, sem diferença no escore total quando comparadas a não usuárias. CONCLUSÕES: as mulheres na pós-menopausa usuárias e não usuárias de TH, atendidas em UBS, não apresentaram diferenças na QV global.

PURPOSE: to evaluate the quality of life of post-menopause women, users and non-users of hormonal therapy (HT), in a Healthcare Unit in Franca, São Paulo, Brazil. METHODS: a clinical transversal study, carried out with 250 post-menopausal women, with ages from 45 to 70 years old, attended to in Healthcare Units, from September 2007 to August 2008. Participants were divided into two groups: HT users (n=70) and non-users (n=180). Women making continuous HT use for at least six months were considered as users. Sociodemographic and clinical characteristics have been evaluated. Blatt-Kupperman’s menopausal index has been applied to assess climacteric symptoms, and the Women’s Health Questionnaire (WHQ), to assess their quality of life. Fisher’s exact test or χ2 and Mann-Whitney and Kruskal-Wallis’s tests have been used for the statistical analysis. RESULTS: no significant difference has been found in the comparison of groups, concerning age, menarche, menopause, parity and body mass index. It has been seen that 67.2% of the women were married, 83.2% had attended primary school and 53.2% were housewives, with no difference between the groups. HT users reported lower frequency of climacteric symptoms (BKMI) with moderate and marked intensity, as compared to non-users (p<0.001). Even though HT users presented lower average score in cognitive deficit (p<0.001), vasomotor symptoms (p=0.04), sleeping problems (p<0.001), attractiveness (p=0.02) from the WHQ, there has been no difference in the total score, as compared to non-users. CONCLUSIONS: post-menopausal women, HT users and non-users, admitted at Healthcare Units, have not presented differences in global quality of life.

Histopathological and immunohistochemical (cytokeratins AE1/AE3) study of the parametrium of patients with early stage cervical cancer.

OBJECTIVE: This study was undertaken in order to evaluate histopathological and immunohistochemical (cytokeratins AE1/AE3) characteristics of parametrial invasion in patients with early stage cervical cancer. STUDY DESIGN: Thirty patients with stage IB squamous cell carcinoma (SCC) of the cervix submitted to radical hysterectomy from November 2001 to September 2002 were prospectively studied. Histopathological studies were undertaken using tissue samples (n=60) taken from the parametrium, whose surgical margins were inked and the entire parametrial tissue was fixed in 10% buffered formalin and embedded in paraffin for further analysis using hematoxylin-eosin (H&E) staining. Specific patterns of parametrial involvement (continuous invasion, parametrial lymphatic vascular space invasion (LVSI) and/or parametrial lymph nodes' (PMLN) metastasis) were recorded. Parametrial samples, in which the histological examination showed no tumor involvement, were immunohistochemically assessed through monoclonal antibodies for cytokeratins AE1/AE3. Clinicopathological characteristics of the patients were also recorded. RESULTS: Patient's mean age was 49+/-10 years (27-73 years). Histopathological analysis (H&E) showed parametrium involvement in 12 patients (40%) of whom 11 (92%) presented parametrial LVSI, 9 (75%) continuous invasion and 4 (33%) PMLN metastasis. Micrometastasis was detected in 3/18 (17%) of the patients with histologically negative parametrium by H&E evaluation. Parametrial involvement detected by H&E was associated with tumor recurrence (p=0.009) and survival (p=0.025). This association was not correlated with the presence of parametrial micrometastasis (p=1.00 and 1.00, respectively). CONCLUSIONS: The process of parametrial spreading in patients with SCC of the cervix may develop several histopathological patterns, which are associated with clinicopathological features and prognosis. Our findings highlight the importance to ink the parametria, which is the only way to define the pattern of tumor spreading. The clinical significance of micrometastasis, detected in patients with histologically negative parametrium by H&E, remains to be clear.

Effect of raloxifene on the vaginal epithelium of postmenopausal women.

OBJECTIVE: The objective was to analyze the effect of raloxifene on the vaginal epithelium of postmenopausal women. STUDY DESIGN: In this non-randomized clinical trial, 80 women (mean age = 60.6 years) were prospectively studied. Forty patients received 60 mg/day of raloxifene (RG), and 40 women constituted a non-treated control group (CG), paired by age and time since menopause. The treated group consisted of patients with osteoporosis of the lumbar spine. Those with a diagnosis of infection in the lower genital tract and using hormone therapy (HT) up to 6 months prior to the study were excluded. Vaginal smears were collected at baseline and after 6 months of intervention. The vaginal maturation value (VMV) was determined, and counts of superficial, intermediate and parabasal cells were performed. Smears were analyzed by only one cytopathologist who was blinded to patient data. The t-test, Wilcoxon test, and Chi-Squared test were used in the statistical analysis. RESULTS: The study groups were homogeneous regarding age, time since menopause, parity, HT use, smoking, and body mass index. No statistically significant differences were observed in VMV median values (RG, 39.7 and 35.7; CG, 50.0 and 50.0, respectively) or in the percentage of superficial, intermediate and parabasal cells between the groups at baseline and after 6 months (p>0.05). There was no significant correlation between VMV and age, time since menopause, previous HT use, or body mass index, in either of the groups. CONCLUSION: Treatment with raloxifene for 6 months has no effect on the maturation of the vaginal epithelium in postmenopausal women with osteoporosis.

Tratamento da neoplasia trofoblástica gestacional de alto risco resistente à quimioterapia / Therapy of high risk gestational trophoblastic neoplasia resistant to chemotherapy

Neoplasia trofoblástica gestacional (NTG) de alto risco inclui os estadios I, II ou III: escore de risco sete ou mais ou estadio IV da classificação atual FIGO 2000. Embora bem estabelecidos os protocolos EMA-CO como primeira linha e EP-EMA como primeira ou segunda linha de tratamento, aproximadamente 30 porcento das pacientes com NTG de alto risco desenvolvem resistência ou apresentam recidiva seguindo a remissão. Ao constatar-se a resistência ou recidiva, deve-se proceder à reavaliação imediata da paciente, com base no Sistema de Estadiamento FIGO 2000, para clarear o tratamento de resgate em tempo hábil - poliquimioterapia e/ou cirurgia e/ou radioterapia. Não existe protocolo ideal para o tratamento de pacientes com NTG de alto risco resistente à quimioterapia. Assim sendo, o tratamento deve ser individualizado de acordo com a condição clínica da paciente e a experiência do centro especializado. Este estudo refere-se à NTG de alto risco resistente à quimioterapia, apresentando os principais regimes alternativos de poliquimioterapia, a quimioterapia de alta dose, o tratamento de consolidação, o papel da cirurgia e da radioterapia e o seguimento pós-remissão completa.

Avaliação da resposta à quimioterapia primária em amostra de mulheres brasileiras com tumores de mama localmente avançados / Evaluation of response to primary chemotherapy in Brazilian patients with locally advanced breast cancer

OBJETIVO: avaliar a resposta loco-regional à quimioterapia primária nas pacientes com câncer de mama nos estadios II e III. MÉTODOS: foi realizado um estudo clínico retrospectivo e analítico de 97 pacientes no estadios II e III, no período de janeiro de 1993 a dezembro de 2004, submetidas a três ou quatro ciclos de quimioterapia primária com 5-fluorouracil (500 mg/m²), epirrubicina (50 mg/m²) e ciclofosfamida (500 mg/m²) ou doxorrubicina (50 mg/m²) e ciclofosfamida (500 mg/m²) e posteriormente ao tratamento loco-regional cirúrgico conservador ou radical. Para estudo da associação entre as variáveis (idade, estado menopausal, volume tumoral pré-quimioterapia, estado axilar, estádio, esquema terapêutico e número de ciclos) foram utilizados os testes do chi2 e o exato de Fisher. Para as variáveis quantitativas (volume tumoral pelo estudo anátomo-patológico e volume tumoral clínico pós-quimioterapia) foi utilizado o coeficiente de correlação de Pearson. O nível de significância utilizado foi de 5 por cento. RESULTADOS: a média de idade da população estudada foi de 52,2 anos. No estádio II, tivemos 56,8 por cento dos casos e no estádio III, 43,2 por cento. Aproximadamente metade das pacientes receberam FEC50 e 50 por cento, AC. Obtivemos uma resposta clínica objetiva com o tratamento quimioterápico primário em 64,9 por cento dos casos. A resposta clínica completa ocorreu em 12,3 por cento das pacientes; já a resposta patológica completa aconteceu em 10,3 por cento dos casos. Observamos uma correlação significante entre o número de ciclos e a resposta à quimioterapia primária. Também verificamos uma concordância significante entre a avaliação pelo exame clínico da resposta à quimioterapia primária e o achado anátomo-patológico. CONCLUSÕES: o número de ciclos foi importante para a resposta loco-regional, sendo que as pacientes que receberam maior número de ciclos obtiveram melhores respostas. Também foi possível avaliar a resposta tumoral pelo...

PURPOSE: to evaluate the loco-regional response to primary chemotherapy in patients with breast cancer at stages II and III. METHODS: a retrospective and analytical clinical study carried out in 97 patients with an average age of 52.2 years old, with breast cancer at stages II and III, attended from January 1993 to December 2004, and submitted to 3 to 4 cycles of primary chemotherapy with 5-fluorouracil - 500 mg/m2, epirubicin - 50 mg/m2 and cyclophosphamide - 500 mg/m2 or doxorubicin - 50 mg/m2 e cyclophosphamide - 500 mg/m2, and then to loco-regional surgical conservative or radical surgical treatment. Chi-square and FisherÆs exact tests were used to study the association among the variables (age, menopausal state, pre-chemotherapy tumoral volume, axillary condition, stage, therapeutic scheme and number of cycles), while PearsonÆs correlation coefficient was used for the quantitative variables (tumoral volume according to the anatomo-pathological study and the post-chemotherapy clinical tumoral volume. The significance level was 5 percent. RESULTS: there were 56.8 percent of cases at stage II and 43.2 percent at stage III. Approximately 50 percent of the patients received FEC50 and 50 percent AC. Objective clinical response with primary chemotherapy was obtained in 64.9 percent of the cases. Full clinical response occurred in 12.3 percent of patients, while full pathological response occurred in 10.3 percent of the cases. CONCLUSIONS: there was a statistically significant correlation between the number of cycles and the response to primary chemotherapy. Patients who received 4 cycles had better response than those who received 3 cycles. There was also a statistically significant concordance between the evaluation through clinical examination of the response to primary chemotherapy and the pathological findings. No statistically significant correlation was observed concerning age, menopausal status, tumoral volume, and pretreatment of...

Missing association between telomerase activity and clinicopathological features in patients with early stage carcinoma of the cervix.

OBJECTIVES: This study was undertaken to evaluate the association between the telomerase activity in the tumor and clinicopathological findings in patients with stage IB-IIA (FIGO) carcinoma of the cervix. METHODS: Thirty-eight patients with carcinoma of the cervix submitted to radical hysterectomy were prospectively from January 1998 to November 2001. Samples from the tumor were taken and analyzed by the telomerase PCR-TRAP-ELISA kit. Clinicopathological characteristics such as age, stage, tumor size, grade of differentiation, lymphatic vascular space invasion (LVSI), parametrial involvement and status of pelvic lymph nodes were also recorded. RESULTS: Patient's mean age was 49.3+/-1.99 years (29-76 years). The clinical stage (FIGO) was IB in 35 patients (92.1%) and IIA in 3 patients (7.9%). The histological classification identified squamous cell carcinoma in 33 patients (86.8%) and adenocarcinoma in 5 patients (13.2%). There was no association between age, clinical stage, histological classification, tumor size, grade of differentiation and presence of LVSI with tumoral telomerase activity. The telomerase activity was not associated with the presence of vaginal involvement (P=0.349), parametrium involvement (P=0.916), pelvic lymph node metastasis (P=0.988) or tumoral recurrence (P=0.328) in patients with carcinoma of the cervix. CONCLUSIONS: Telomerase activity in the tumor is not associated with clinicopathological findings or tumor recurrence in patients with early stage cervical carcinoma.

Effects of soy protein and resistance exercise on body composition and blood lipids in postmenopausal women.

OBJECTIVE: To assess the effect of soy protein and progressive resistance training on body composition and lipids in postmenopausal women. DESIGN: In a controlled trial, 46 postmenopausal women were randomized to one of four groups: 25 g of soy protein (SP, n=10), 25 g of soy protein plus resistance exercise (SPE, n=14), 25 g of maltodextrine (placebo) (PL, n=11), or placebo plus resistance exercise (PLE, n=11). Progressive resistance training was held three times a week for 16 weeks and included 8 exercises (3 series of 8-12 repetitions). At baseline and after 16 weeks, body mass index, waist circumference (WC), body fat, muscle mass and serum lipid levels were measured. To confirm isoflavone absorption, urinary concentrations were determined. The t-test of Student and ANOVA were used in the statistical analysis. RESULTS: Subjects were classified as overweight and showed android fat distribution. Urinary isoflavone excretion indicated compliance to soy protein treatment. After 16 weeks of intervention, both SPE and PLE groups showed a significant increase of 1.3 kg in muscle mass and reduction in WC of -1.4 and -2.1cm, respectively (p<0.05). Significant decreases in the mean values of total cholesterol and LDL (-29.0 and -24.0 mg/dL, p<0.001 and p<0.006, respectively) were observed in the users of soy protein alone (SP). CONCLUSIONS: Soy protein supplementation did not influence the indicators of body composition. However, it exerted possible favorable effects on lipid profile in postmenopausal women. The increase in muscle mass and reduction in abdominal fat were correlated with resistance training.