Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients

The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation

Suspected acute toxoplasmosis in pregnant women Suspeita de toxoplasmose aguda em gestantes

OBJECTIVE: To determine the prevalence of reagent serology for suspected acute toxoplasmosis in pregnant women and to describe clinical, laboratory and therapeutic profiles of mothers and their children. METHODS: A retrospective study was conducted with IgM-anti-Toxoplasma gondii-reagent pregnant women and their children who attended the public health system in the state of Paraná, Southern Brazil, from January 2001 to December 2003. Information were obtained from clinical, laboratory (ELISA IgM/IgG) and ultrasonographic data and from interviews with the mothers. To test the homogeneity of the IgM indices in relation to the treatment used, the Pearson's Chi-square test was applied. Comparisons were considered significant at a 5% level. RESULTS: Two hundred and ninety (1.0%) cases of suspected IgM-reagent infection were documented, with a prevalence of 10.7 IgM-reagent women per 1,000 births. Prenatal care started within the first 12 weeks for 214/290; 146/204 were asymptomatic. Frequent complaints included headaches, visual disturbance and myalgia. Ultrasonography revealed abnormalities in 13 of 204 pregnancies. Chemoprophylaxis was administered to 112/227; a single ELISA test supported most decisions to begin treatment. Pregnant women with IgM indices =2.000 tended to be treated more often. Among exposed children, 44/208 were serologically followed up and all were IgG-reagent, and three IgM-reagent cases showed clinical symptoms. CONCLUSIONS: The existence of pregnant women with laboratorially suspected acute toxoplasmosis who were not properly followed up, and of fetuses that were not adequately monitored, shows that basic aspects of the prenatal care are not being systematically observed. There is need of implementing a surveillance system of pregnant women and their children exposed to T. gondii.<br>OBJETIVO: Determinar a prevalência de gestantes com sorologia reagente suspeita de toxoplasmose aguda e descrever as variáveis maternas e do concepto relacionadas ao perfil clínico, laboratorial e terapêutico. MÉTODOS: Estudo retrospectivo com gestantes IgM anti-Toxoplasma gondii reagentes e conceptos atendidos em serviço público de saúde do Paraná, de janeiro/2001-dezembro/2003. Foram obtidas informações a partir de dados dos registros clínicos, laboratoriais (ELISA IgM/IgG), ultrassonográficos e de entrevista materna. Para testar a homogeneidade dos indices de IgM em relação ao tratamento usado, aplicou-se o qui-quadrado de Pearson. O nível de significância adotado foi de 5%. RESULTADOS: Ocorreram 290 casos (1,0%) IgM reagentes, evidenciando prevalência de 10,7 gestantes com sorologia reagente a cada 1.000 nascimentos. Duzentos e quatorze de 290 gestantes iniciaram o pré-natal até a 12ª semana de gestação; 146/204 foram assintomáticas; cefaléia, distúrbios visuais e mialgia foram queixas freqüentes; 13/204 gestantes apresentaram anormalidades ao ultrassom; 112/227 gestantes receberam quimioprofilaxia; um único teste ELISA apoiou a maioria das tomadas de decisão para a quimioprofilaxia. Houve tendência em tratar gestantes com índices de IgM=2.000. Dentre as crianças expostas, 44/208 tiveram algum acompanhamento sorológico, das quais todas foram IgG reagentes e três casos IgM reagentes apresentaram manifestações clínicas. CONCLUSÕES: A existência de gestantes com suspeita laboratorial de toxoplasmose aguda não devidamente investigada e de conceptos sem monitoração adequada evidenciam que aspectos fundamentais da assistência pré-natal não estão sendo sistematicamente observados. Aponta-se a necessidade de implementar o sistema de vigilância para gestantes e crianças expostas ao T. gondii

Avaliação da aplicação do protocolo de triagem pré-natal para toxoplasmose em Belo Horizonte, Minas Gerais, Brasil: estudo transversal em puérperas de duas maternidades Evaluation of prenatal screening for toxoplasmosis in Belo Horizonte, Minas Gerais State, Brazil: a cross-sectional study of postpartum women in two maternity hospitals

Foi realizado estudo transversal, em duas maternidades públicas de Belo Horizonte, Minas Gerais, Brasil, com entrevista de 420 puérperas, de agosto de 2004 a maio de 2005, para avaliar a aplicação do protocolo de triagem pré-natal para toxoplasmose implantado, e as orientações oferecidas às gestantes suscetíveis. A cobertura do pré-natal foi de 98%, e da primeira triagem sorológica de 97%. O início do pré-natal e a realização da primeira sorologia ocorreram em média com 16 semanas. Foram identificadas 163 gestantes suscetíveis à toxoplasmose: 44% não repetiram a sorologia, e 42% alegaram não ter recebido orientações para prevenção da toxoplasmose. O início precoce do pré-natal e um maior número de consultas foram associados à repetição da sorologia e ao recebimento de orientações. As informações oferecidas foram: evitar contato com gatos (95%), não ingerir ou manipular carne crua (70%) e lavar cuidadosamente as hortaliças (53%). Concluiu-se que a adesão inadequada ao protocolo de triagem pré-natal de toxoplasmose encontrada no estudo pode gerar gastos financeiros sem melhoria na qualidade do cuidado perinatal.<br>This cross-sectional study of 420 women in two public maternity hospitals from August 2004 to May 2005 evaluated the application of a prenatal toxoplasmosis serological screening protocol in Belo Horizonte, Minas Gerais State, Brazil, and the information provided to susceptible pregnant women. Ninety-eight percent of women received prenatal care and 97% underwent the initial serological screening test, at an average of 16 weeks gestational age. The initial testing identified 163 women as susceptible to toxoplasmosis: 44% of these did not undergo repeat serological testing, and 42% of them did not remember having received information on the prevention of toxoplasmosis infection. Early prenatal care and a high number of prenatal visits were associated with repeat serological testing and orientation regarding its implications. Orientation on risk factors included: avoiding contact with cats (95%), not handling or eating raw meat (70%), and washing vegetables carefully before consumption (53%). Inadequate adherence to the prenatal screening protocol for toxoplasmosis, as detected in this study, may be generating health system costs without a corresponding improvement in the quality of perinatal care