Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer.

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression of hypoxia-inducible factor 2A and with poor prognosis in patients with locally advanced breast cancer.

Expression of aldehyde dehydrogenase after neoadjuvant chemotherapy is associated with expression of hypoxia-inducible factors 1 and 2 alpha and predicts prognosis in locally advanced breast cancer

OBJECTIVE: To analyze the expression of hypoxia-inducible factors (hypoxia-inducible factor 1A and hypoxia-inducible factor 2A) and aldehyde dehydrogenase proteins in patients with locally advanced breast carcinoma who were subjected to neoadjuvant chemotherapy. METHODS: We included 90 patients with histologically confirmed stage II and III breast carcinoma who were treated with neoadjuvant chemotherapy between 2000 and 2005. Immunohistochemistry for aldehyde dehydrogenase, hypoxia-inducible factor 1A, and hypoxia-inducible factor 2A was performed before and after neoadjuvant chemotherapy. We analyzed the influence of clinical and pathological features on clinical and pathological response, disease-free survival, and overall survival. RESULTS: An objective clinical response to neoadjuvant chemotherapy was observed in 80% of patients, with 12% showing a complete pathological response. Among all clinical and pathological parameters, only the expression of hypoxia-inducible factor 1A was associated with a pathological response. A positive association was found between expression of aldehyde dehydrogenase and that of hypoxia-inducible factor 1A before and after chemotherapy. Aldehyde dehydrogenase expression was associated with expression of hypoxia inducible-factor 2A in tumors after neoadjuvant treatment. In a univariate analysis, prognosis was influenced by age, pathological response, metastasis to axillary lymph nodes after neoadjuvant chemotherapy, overexpression of hypoxia-inducible factor 2, and the presence of aldehyde dehydrogenase-positive cells within the primary tumor after neoadjuvant chemotherapy. In a multivariate analysis, only age and the presence of aldehyde dehydrogenase-positive cells after chemotherapy were associated with reduced overall survival. CONCLUSION: The presence of aldehyde dehydrogenase-positive cells within the residual tumor after neoadjuvant chemotherapy is associated with an increase in the expression ...

Safety and efficacy of gemcitabine plus cisplatin combination in pretreated metastatic breast cancer patients.

Metastatic breast cancers (MBC) previously treated with anthracyclines (A) and taxanes (T) have a complicated management. Gemcitabine (G)-cisplatin (C) combinations have been used as synergistic salvage therapy in MBC and are considered as another option for patients with important symptoms and aggressive visceral disease. We analyzed the safety and efficacy of GC in AT-pretreated MBC, as well as overall survival (OS) and time to progression (TTP). Forty-nine subjects received IV G 750 mg/m(2) and C 30 mg/m(2), both d1 and d8 every 3 weeks. Response evaluation was performed every second cycle and in the end of treatment. GC protocol was the first-line palliative chemotherapy in half of the cases, and median number of cycles/patient were 4(2-12). Lung (75.5%) was the most frequent site of metastasis. Most of the patients related clinical improvement with chemotherapy with minimal/mild tolerable collateral effects in 85.7% of cases. Following 34 months, mean OS/TTP was 13.12/6.6 months. Objective-responded patients (40.3%) were statistically associated with the improvement in symptoms after CT (P < 0.01), and OS was directly correlated with chemotherapy response (P < 0.01). HER-2 overexpression was a prognostic factor with reduced OS (P = 0.01). GC protocol was effective and tolerable in objective-responded patients.

Expression of Hypoxia-inducible factor 1-α and vascular endothelial growth factor-C in locally advanced breast cancer patients.

BACKGROUND: Locally advanced breast cancers are more prevalent in underdeveloped countries. Targeted therapy has been improved to identify hallmarks that are specific to these subtypes of tumors. OBJECTIVES: We aimed to prospectively assess the expression of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C in locally advanced breast cancer patients. METHODS: Thirty women underwent incisional biopsies for the histopathological diagnosis of breast carcinoma and participated in neoadjuvant chemotherapy. The association of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C with age, tumor size, histological grade, clinical staging, hormonal and axillary status, clinical and pathological response after neoadjuvant chemotherapy, expression of estrogen and progesterone receptors, and the presence of c-erbB-2 antigen was studied. RESULTS: Hypoxia inducible factor-1 α expression and Vascular endothelial growth factor-C expression were observed in 66.7% and 63.3% of all patients, respectively, and were marginally associated with each other (p = 0.06). Among the studied variables, only positive axillary status was associated with the presence of HIF-1α (p = 0.02). Complete pathological response was significantly associated (p = 0.04) with the expression of vascular endothelial growth factor-C prior to neoadjuvant chemotherapy. CONCLUSION: We concluded that Hypoxia inducible factor-1 α was associated with a poor prognosis and that vascular endothelial growth factor-C could be used as a predictive factor in locally advanced breast cancer patients with complete pathological response after neoadjuvant chemotherapy.

Expression of Hypoxia-inducible factor 1-α and Vascular endothelial growth factor-C in locally advanced breast cancer patients

BACKGROUND: Locally advanced breast cancers are more prevalent in underdeveloped countries. Targeted therapy has been improved to identify hallmarks that are specific to these subtypes of tumors. OBJECTIVES: We aimed to prospectively assess the expression of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C in locally advanced breast cancer patients. METHODS: Thirty women underwent incisional biopsies for the histopathological diagnosis of breast carcinoma and participated in neoadjuvant chemotherapy. The association of Hypoxia inducible factor-1 α and vascular endothelial growth factor-C with age, tumor size, histological grade, clinical staging, hormonal and axillary status, clinical and pathological response after neoadjuvant chemotherapy, expression of estrogen and progesterone receptors, and the presence of c-erbB-2 antigen was studied. RESULTS: Hypoxia inducible factor-1 α expression and Vascular endothelial growth factor-C expression were observed in 66.7 percent and 63.3 percent of all patients, respectively, and were marginally associated with each other (p = 0.06). Among the studied variables, only positive axillary status was associated with the presence of HIF-1α (p = 0.02). Complete pathological response was significantly associated (p = 0.04) with the expression of vascular endothelial growth factor-C prior to neoadjuvant chemotherapy. CONCLUSION: We concluded that Hypoxia inducible factor-1 α was associated with a poor prognosis and that vascular endothelial growth factor-C could be used as a predictive factor in locally advanced breast cancer patients with complete pathological response after neoadjuvant chemotherapy.

[Knowledge, practice and attitude about breast self-exam from women of a Northeastern municipality, Brazil]. / Conhecimento, prática e atitude sobre o autoexame das mamas de mulheres de uma cidade do Nordeste do Brasil.

PURPOSE: To assess the knowledge, attitude and practice of breast self-examination (BSE) of women from the municipality of São Luís (MA), Brazil, and associated socio-demographic variables. METHODS: Prospective and cross-sectional study, with conglomerate sampling, in which 552 women from 14 census sections of São Luís were included during the period from January to September 2003. The knowledge, attitude and practice (dependent variables) were evaluated by means of analysis of the responses of the women as "adequate" or "inadequate". The main independent variables were: age, schooling, family income and marital and menopausal status. The χ² test was used to determine the association between categorical variables and the measurement of the crude/adjusted Odds Ratio (OR) after multivariate analysis by means of logistic regression. RESULTS: Although 1/3 of the studied population did not know about BSE, the group of women who were informed about it showed adequate knowledge (60.9%), practice (59.5%) and attitude (90%). The family history of breast cancer (8.9%) was not associated with better knowledge and practice. The media (63.6%) was found to be important in disseminating information about BSE. After multivariate analysis, women with a partner (OR=1.9) presented more adequate knowledge; women older than 50 years (OR=11.7) had a better attitude towards BSE; women with more than five years of schooling (OR=2) and with a partner (OR=1.7) were associated with a more correct practice of BSE. CONCLUSION: Most of the patients know and practice the BSE in São Luís and their attitude towards the procedure is extremely positive. There was a great participation of the media in the dissemination of information concerning BSE.

Genital manifestation of graft-vs.-host disease: a series of case reports.

INTRODUCTION: After hematopoietic stem cell transplantation (HSCT), many patients present genital graft-vs.-host disease (GVHD) that can culminate with sexual problems, which are poorly dimensioned. AIM: We hope to draw attention to the need to perform genital biopsy to diagnose genital GVHD, and thus to call attention to the need to incorporate careful attention to sexual health in the treatment of these patients. METHODS: Five allogeneic stem cell transplant recipients complaining of coital pain after HSCT were clinically diagnosed for genital GVHD. Genital biopsies were given for histological analysis, and microphotographs of the corresponding marked field in the slide were taken. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the histological findings. A literature search was performed in PubMed/MEDLINE (1966-2009) for cross-sectional and cohort studies or trials related to genital GVHD. Expert opinions peer reviews and case reports were also considered. MAIN OUTCOME MEASURES: HSCT, genital GVHD, genital biopsy. RESULTS: The biopsy showed evidence of dilated apoptotic cells in the basal layer and detachment of the epithelial lining of the mucosa, hyalinization and thickening of collagen fibers, capillary ectasia, and mononuclear inflammatory infiltrate of the submucosa. Three patients presented vulval lesion such as leucoplasia and ulcer on the large lip. Histological analyses showed evidence of epithelial hyperplasia and influx of inflammatory cells to the epithelial surface, intercellular edema and spongiosis, apoptotic bodies on the basal layer of the epithelium, spongiosis, and nuclear vacuolization. A common treatment based on corticotherapy resulted in complete remission of coetaneous or mucous genital lesions in all five patients. CONCLUSION: Genital biopsy is important to differentially diagnose GVHD and secondary symptoms due to hypoestrogenism. Prevention is the most important step in controlling the evolution GVHD in the vagina to prevent vaginal obstruction and sexual dysfunction.

Conhecimento, prática e atitude sobre o autoexame das mamas de mulheres de uma cidade do Nordeste do Brasil / Knowledge, practice and attitude about breast self-exam from women of a Northeastern municipality, Brazil

OBJETIVO: avaliar o conhecimento, a atitude e a prática do autoexame das mamas (AEM) em mulheres do município de São Luís (MA) e os fatores sociodemográficos relacionados. MÉTODOS: estudo transversal, prospectivo, com amostragem por conglomerados, no qual foram incluídas 552 mulheres de 14 setores censitários em São Luís, no período de Janeiro a Setembro de 2003. O conhecimento, a atitude e a prática (variáveis dependentes) foram avaliados pela análise das respostas das mulheres em "adequado" ou "inadequado". As principais variáveis independentes foram: idade, escolaridade, renda familiar, situação conjugal e status menopausal. Foi realizado o teste do χ2 para a associação entre variáveis categóricas e a mensuração do Odds Ratio (OR) bruto e ajustado após análise multivariada por regressão logística. RESULTADOS: embora 1/3 da população estudada não tivesse conhecimento do AEM, o grupo de mulheres que eram informadas sobre a existência do exame possuía conhecimento (60,9 por cento), prática (59,5 por cento) e atitude (90 por cento) adequados. O histórico familiar para câncer de mama (8,9 por cento) não esteve associado a maior conhecimento e prática. A mídia mostrou-se de grande importância (63,6 por cento) na disseminação da informação do AEM. Após análise multivariada, a mulher com parceiro (OR=1,9) apresentou maior adequação do conhecimento; o grupo de mulheres com idade maior que 50 anos (OR=11,7) teve melhor atitude quanto ao AEM; a escolaridade maior que cinco anos (OR=2) e mulher com parceiro (OR=1,7) estiveram associadas à prática mais correta do AEM. CONCLUSÃO: a maioria das pacientes conhece e pratica o AEM em São Luís e a atitude delas frente ao procedimento é extremamente positiva. Houve uma grande participação da mídia na propagação da informação sobre o AEM.

PURPOSE: to assess the knowledge, attitude and practice of breast self-examination (BSE) of women from the municipality of São Luís (MA), Brazil, and associated socio-demographic variables. METHODS: prospective and cross-sectional study, with conglomerate sampling, in which 552 women from 14 census sections of São Luís were included during the period from January to September 2003. The knowledge, attitude and practice (dependent variables) were evaluated by means of analysis of the responses of the women as "adequate" or "inadequate". The main independent variables were: age, schooling, family income and marital and menopausal status. The χ2 test was used to determine the association between categorical variables and the measurement of the crude/adjusted Odds Ratio (OR) after multivariate analysis by means of logistic regression. RESULTS: although 1/3 of the studied population did not know about BSE, the group of women who were informed about it showed adequate knowledge (60.9 percent), practice (59.5 percent) and attitude (90 percent). The family history of breast cancer (8.9 percent) was not associated with better knowledge and practice. The media (63.6 percent) was found to be important in disseminating information about BSE. After multivariate analysis, women with a partner (OR=1.9) presented more adequate knowledge; women older than 50 years (OR=11.7) had a better attitude towards BSE; women with more than five years of schooling (OR=2) and with a partner (OR=1.7) were associated with a more correct practice of BSE. CONCLUSION: most of the patients know and practice the BSE in São Luís and their attitude towards the procedure is extremely positive. There was a great participation of the media in the dissemination of information concerning BSE.

Impact of surgical staging in locally advanced cervical cancer and subsequent chemotherapy.

BACKGROUND: Surgical staging (SS) is the gold standard for determination of the true extent of a patient's disease and is an important prognostic factor in cervical cancer. We investigated whether lymph node dissection (LND) prior to chemotherapy (CT) followed by radical surgery (RS) could modified overall (OS) and disease-free survival (DFS). METHODS: We performed a cohort analysis of 98 patients with cervical carcinoma. The experimental group consisted of 36 patients who underwent SS followed by neoadjuvant chemotherapy, and then by RS (objective response) or chemo-radiation therapy (with or without subsequent surgery when not possible). The control group consisted of 62 similarly treated patients without pretreatment SS. The value of this procedure as a diagnostic tool in defining the extent of disease was evaluated. Furthermore, LND/CT-associated treatment complications and the impacts on OS and DFS were also evaluated. RESULTS: Fourteen (38.9%) patients had pelvic LN metastases and three (8.3%) patients had pelvic and para-aortic LN metastases. The 39-month OS and DFS rates for the current study were 80.6% for the staged group and 52% for non-staged treatment (P < 0.001). CONCLUSION: SS in cervical cancer is a feasible and safe pretreatment procedure, and when associated with CT, it improves OS and DFS.

Clinical criteria as predictive factors of response to primary hormone therapy in locally advanced breast cancer.

This study investigates the efficacy of clinical criteria in selecting patients for primary tamoxifen therapy. A total of 60 breast cancer patients with large primary tumors and unknown hormonal receptor status were subjected to primary hormone therapy. Inclusion criteria were age over 60 years old or menopausal status for at least 10 years and no clinical evidence of inflammatory disease and fast tumor growth. The objective response rate was 55%. There was a positive correlation between the lack of clinical response and axillary lymph node metastasis (p = 0.009). Patients with objective response had significantly improved disease-free (p = 0.045) and overall (p = 0.0002) survival over those who did not have response to hormonal therapy. In multivariate analysis, the clinical response to therapy was the most powerful prognostic factor. This analysis demonstrates that clinical criteria were very effective predictor of response to neo-adjuvant hormone therapy in large breast tumors for postmenopausal women. Response to therapy is the major prognostic factor in primary tamoxifen-treated breast cancer.

Uso do trastuzumabe na gravidez / Use of trastuzumab during pregnancy

O uso do trastuzumabe, anticorpo antimonoclonal contra o receptor do fator de crescimento epidérmico HER-2, tem sido utilizado no tratamento do carcinoma mamário de pacientes que superexpressam esta proteína. Relatos de casos divergem quanto à presença ou ausência de efeitos adversos na gravidez. Quando presentes, os mais encontrados no feto foram: oligo ou anidrâmnio, insuficiência renal, síndrome de angústia respiratória e óbito fetal/neonatal. Esta revisão discutiu as vias etiopatológicas possíveis deste fármaco em causar tais efeitos e sugeriu uma propedêutica de seguimento dessas pacientes.

The use of trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2, has been a useful therapy in the treatment of breast cancer patients that overexpress such protein. Published case reports with different results regarding the presence or absence of adverse effects in pregnancy are shown. If present, the most reported ones were: oligo or anydramnios, renal insufficiency, respiratory distress syndrome, and fetal/neonatal death. This review discussed the ethiopathologic pathways of this drug in causing such effects and suggested a follow-up protocol for these patients.

Impacto prognóstico da recorrência local em pacientes com câncer inicial de mama submetidas a tratamento conservador / The prognostic impact of local recurrence on early breast cancer patients treated with breast conserving therapy

OBJETIVO: investigar o impacto da recorrência local no prognóstico de pacientes com câncer de mama em estágio inicial tratado com cirurgia conservadora. MÉTODO: foi realizado estudo de coorte retrospectivo incluindo 192 pacientes com câncer de mama em estágio inicial submetidas a tratamento conservador. Utilizando critérios clínicos e patológicos (tempo para recorrência, local da recorrência e tipo histológico) classificamos as pacientes em três grupos. O grupo de recorrência local verdadeira (RLV), o grupo de novo tumor primário (NP) e o grupo livre de recorrência local (LRL). Foi comparada a evolução entre os diferentes grupos. RESULTADOS: menor idade e uma maior proporção de pacientes na pré-menopausa foram observas no grupo NP. A presença de RLV foi o mais importante fator prognóstico sendo que 40 por cento das pacientes deste grupo desenvolveram doença metastática sincrônica à recorrência local. Doença metastática ocorreu em 28,5 por cento e 4,7 por cento nos grupos NP e LRL, respectivamente (p< 0,0001). A taxa de sobrevida global em cinco anos foi de 75 por cento no grupo RLV, 100 por cento no grupo NP e 98,2 por cento no grupo LRL (p< 0,0001). Tipo histológico, margens cirúrgicas, metástase em linfonodos axilares e expressão de receptores hormonais não foram preditores de recorrência local. Pacientes que não foram submetidas a hormonioterapia adjuvante e a idade foram os mais importantes fatores preditores de recorrência local. CONCLUSÃO: recorrência local verdadeira é um fator prognóstico em pacientes com câncer de mama inicial tratado com cirurgia conservadora. A idade é o mais importante fator na recorrência local neste grupo de pacientes. O alto risco recorrência local nestas pacientes é um fator limitante da cirurgia conservadora.

BACKGROUND: In order to investigate the impact of local recurrence on breast cancer patient prognosis, we developed this study. METHOD: A retrospective cohort study including 192 patients with early stage breast cancer subjected to breast conserving surgery (BCT) was performed to evaluate the local recurrence pattern and its role on disease progression. Using clinical and pathological criteria (time for recurrence, site of local recurrence and histological type) we classified patients as true local recurrence (TR group), new primary tumor (NP group), and patients free of local recurrence (FLR group). We compared the clinical course among these groups. RESULTS: Patients classified as NP are associated with young age and pre-menopausal status. The presence of TR is the most important predictive factor of prognosis and 40 percent of patients presented synchronic metastatic disease. The metastatic disease occurred in 28.5 percent and 4.7 percent of patients in the NP and FLR groups, respectively (p< 0.0001). Five-year overall survival rate was 75 percent in the TR group, 100 percent in the NP group and 98.2 percent in the FLR group (p< 0.0001). The Histological type and grade, margins status, lymph node metastasis and hormonal receptors were not predictive factors of local recurrence. Patients who were not submitted to hormonal therapy and young age are the most important predictive factors of local recurrence. CONCLUSION: True local recurrence had an influence on overall survival in patients with early breast cancer and the main risk factor for local recurrence was young age. The high-risk incidence for recurrence after BCT in such patients is a limiting factor of therapy.

Idade como fator independente de prognóstico no câncer de mama / Age as an independent prognostic factor in breast cancer

OBJETIVO: comparar as características epidemiológicas e clínicas e a evolução pós-tratamento de mulheres com câncer de mama diagnosticadas antes ou após os 40 anos de idade. MÉTODOS: foi realizado um estudo retrospectivo, tipo caso-controle, com análise de informações obtidas dos prontuários de pacientes atendidas entre janeiro de 1994 e junho de 2004. Excluímos os casos com carcinomas intraductais e no estádio IV. Foram formados três grupos: pacientes com menos de 40 anos no diagnóstico (n=72), pacientes entre 40 e 50 anos (n=68) e pacientes com mais de 50 anos (n=75). Foram coletadas e analisadas informações sobre a idade no momento do diagnóstico, maior diâmetro das lesões, estadiamento clínico, tipo, grau histológico, presença de receptores hormonais e o estado dos linfonodos. O teste do chi2 foi empregado para variáveis qualitativas. Para as variáveis quantitativas que não apresentam distribuição normal (como número de gânglios axilares acometidos por metástases e tempo de seguimento), foi utilizado o teste de Kruskal-Wallis. Para a construção das curvas de sobrevida livre de doença e sobrevida global, foi utilizado o teste log-rank. RESULTADOS: não houve diferença na distribuição por estádios, no grau de diferenciação tumoral ou na distribuição dos tipos histológicos, na expressão de receptores de estrogênio ou c-erb-B2 entre os grupos. Encontramos diferença na expressão de receptores de estrogênio, que foi menos freqüente no grupo com menos de 40 anos em relação ao grupo com mais de 50 anos (36,2 versus 58,4 por cento). Não houve diferença nos diâmetros tumorais, que foram em média de 5,1, 4,7 e 5 cm. Não encontramos diferença nas taxas de acometimento de linfonodos axilares, que foram de 63,9, 46,9 e 50 por cento, respectivamente nas pacientes com menos de 40 anos, pacientes entre 40 e 50 anos e pacientes com mais de 50 anos. A média de seguimento foi de 54 meses nos três grupos. Houve recidiva da doença em 22,6 por cento das...

PURPOSE: to compare the epidemiologic and clinical characteristics, and the follow-up of breast cancer in women diagnosed under and over 40 years of age. METHODS: a retrospective study, case-control type, with analysis of information obtained from medical records of patients attended from January 1994 to June 2004. Cases of intraductal carcinoma and at stage IV were excluded. Three groups were formed: patients under 40 years old at the diagnosis (n=72); patients between 40 and 50 (n=68) and patients over 50 (n=75). Data about age at the moment of diagnosis, lesion largest diameter, clinical stage, type, histological grade, presence of hormonal receptors and state of the lymph nodes were collected and analyzed. The chi2 test was used for qualitative variables. For quantitative variables without normal distribution (such as number of axillary nodes with metastasis and follow-up duration), the Kruskal-Wallis' test was used. For delineating the curves of free-of-disease and global survival, the log-rank test was used. RESULTS: there was no difference among the groups in the stage distribution, concerning the tumoral differentiation grade or in the distribution of histological types, and in the estrogen receptor and c-erb-B2 expression. Difference was found in the RP expression, which was less frequent in the group of patients under 40, than in the group of patients over 50 (36.2 percent versus 58.4 percent) respectively. There was no difference among the groups in the mean tumoral diameter (5.1, 4.7 and 5 cm, respectively). There was also no difference among the groups, concerning the rate of axillary lymph node metastasis (63.9, 46.9 and 50 percent, respectively). The average follow-up was 54 months for all the groups. Disease recurrence occurred in 22.6 percent of patients under 40 years old, in 60 percent of patients between 40 and 50, and in 22.6 percent of patients over 50, with a significant difference among groups (p<0.0001). Death...

Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens.

OBJECTIVES: To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. METHODS: From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups RESULTS: The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p=0.2 and p=0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (p=0.6). CONCLUSION: Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration.

[Age as an independent prognostic factor in breast cancer]. / Idade como fator independente de prognóstico no câncer de mama.

PURPOSE: to compare the epidemiologic and clinical characteristics, and the follow-up of breast cancer in women diagnosed under and over 40 years of age. METHODS: a retrospective study, case-control type, with analysis of information obtained from medical records of patients attended from January 1994 to June 2004. Cases of intraductal carcinoma and at stage IV were excluded. Three groups were formed: patients under 40 years old at the diagnosis (n=72); patients between 40 and 50 (n=68) and patients over 50 (n=75). Data about age at the moment of diagnosis, lesion largest diameter, clinical stage, type, histological grade, presence of hormonal receptors and state of the lymph nodes were collected and analyzed. The chi2 test was used for qualitative variables. For quantitative variables without normal distribution (such as number of axillary nodes with metastasis and follow-up duration), the Kruskal-Wallis' test was used. For delineating the curves of free-of-disease and global survival, the log-rank test was used. RESULTS: there was no difference among the groups in the stage distribution, concerning the tumoral differentiation grade or in the distribution of histological types, and in the estrogen receptor and c-erb-B2 expression. Difference was found in the RP expression, which was less frequent in the group of patients under 40, than in the group of patients over 50 (36.2% versus 58.4%) respectively. There was no difference among the groups in the mean tumoral diameter (5.1, 4.7 and 5 cm, respectively). There was also no difference among the groups, concerning the rate of axillary lymph node metastasis (63.9, 46.9 and 50%, respectively). The average follow-up was 54 months for all the groups. Disease recurrence occurred in 22.6% of patients under 40 years old, in 60% of patients between 40 and 50, and in 22.6% of patients over 50, with a significant difference among groups (p<0.0001). Death caused by the disease was higher among patients under 40 (46.9%) than among patients between 40 and 50 (26.9%) and over 50 (22.6%), p=0.0019. The logistic analysis showed that 'age under 40' and the 'presence of more than one metastatic axillary node' were independent death risk factors. CONCLUSIONS: age under 40 is an independent risk factor for breast cancer. The traditional prognostic indicators, such as stage, tumoral diameter, axillary involvement and presence of hormonal receptors are not associated with the disease evolution.

Picrosirius-polarization staining method as an efficient histopathological tool for collagenolysis detection in vesical prolapse lesions.

The Picrosirius-polarization method has been indicated as a selective histochemical stain for collagen detection in tissue sections. This method can also be of value for studying collagen degradation given that, under polarized light, collagen displays birefringence due to its molecular order. The aim of this study is to highlight this staining method as an additional instrument for a rapid and excellent confirmatory diagnosis of the presence of collagenolysis in connective tissue in the vaginal wall with vesical prolapse lesion, in tissue sections. Dramatic changes in collagen morphology were found in vaginal mucosa in vesical prolapse disorder: they were weakly stained by Sirius red and under polarized light appeared as thin, pale (weakly birefringent), greenish, and with fibers more scattered, while the histoarchitecture of the organ showed a disrupted appearance. Thus, in the present study, we showed in vaginal mucosa in the vesicle prolapse that corroded collagenous framework appears as fragmentary and irregularly separated collagenous structures, that are weakly birefringent, corresponding to a molecular disorganization of these fibers caused by collagenolysis.