Thymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients.

Thymidylate synthase (TYMS) is an important enzyme for 5-fluorouracil (5-FU) metabolism in metastatic colorectal cancer (mCRC) patients. The search for this enzyme in circulating tumor cells (CTCs) can be a powerful tool to follow-up cancer patients. mCRC patients were enrolled before the beginning of 5-FU-based chemotherapy. The blood was filtered on Isolation by Size of Epithelial Tumor Cells (ISET), and the analysis of TYMS expression in CTCs was made by immunocytochemistry. Additionally, we verified TYMS staining in primary tumors and metastases from the same patients. There were included 54 mCRC patients and 47 of them received 5-FU-based chemotherapy. The median CTCs number was 2 per mL. We were not able to analyze immunocytochemistry in 13 samples (9 patients with absence of CTCs and 4 samples due to technical reasons). Therefore, TYMS expression on CTCs was analyzed in 34 samples and was found positive in 9 (26.5%). Six of these patients had tumor progression after treatment with 5-FU. We found an association between CTC TYMS staining and disease progression (DP), although without statistical significance (P = 0.07). TYMS staining in primary tumors and metastases tissues did not have any correlation with disease progression (P = 0.67 and P = 0.42 respectively). Patients who had CTC count above the median (2 CTCs/mL) showed more TYMS expression (P = 0.02) correlating with worse prognosis. Our results searching for TYMS staining in CTCs, primary tumors and metastases suggest that the analysis of TYMS can be useful tool as a 5-FU resistance predictor biomarker if analyzed in CTCs from mCRC patients.

Classificação de pacientes de acordo com o grau de dependência: um desafio para o enfermeiro / Clasificación de los pacientes según el grado de dependência de enfermería del equipo / Classification of patients according to the dependence degree of nursing team

Objetivo: Classificar os pacientes de acordo com o grau de dependência em relação à equipede enfermagem e descrever um plano de cuidado. Método: Pesquisa descritiva, retrospectiva,com abordagem quantitativa, desenvolvida na Clínica Médica de um hospital geraluniversitário no interior de Minas Gerais, de agosto a dezembro de 2013 por acadêmicos deenfermagem. Resultados: Os achados foram discutidos à luz do referencial teórico da autoraFugulin (1994). Foram avaliados 145 pacientes, prevalecendo o grau de dependência semiintensivo,requerendo cuidado contínuo e individualizado. Conclusão: A identificação eclassificação dos pacientes de acordo com sua dependência permitiu à equipe um maiorconhecimento sobre as necessidades humanas básicas apresentadas e possibilitou a construçãode um plano de cuidado para a clientela

Objective: To classify patients according to the degree of dependence on the nursing teamand describe a care plan. Method: a descriptive study, retrospective, with a quantitativeapproach, developed at the Medical Clinic of a university general hospital in Minas Gerais,from August to December 2013 for nursing students. Results: The findings were discussedbased on the theoretical framework of Fugulin author (1994). We evaluated 145 patients,whichever the degree of dependence semi-intensive, requiring continuous and individualizedcare. Conclusion: The identification and classification of patients according to theirdependence allowed the team a better understanding of basic human needs and made possiblethe construction of a care plan for the clientele

Objetivo: clasificar a los pacientes según el grado de dependencia del equipo de enfermería ydescribir un plan de atención. Método: Estudio descriptivo, retrospectivo, con un enfoquecuantitativo, desarrollado en la Clínica Médica de un hospital general universitario en MinasGerais, de agosto a diciembre de 2013 para los estudiantes de enfermería. Resultados: Losresultados fueron discutidos con base en el marco teórico de Fugulin autor (1994). Seevaluaron 145 pacientes, cualquiera que sea el grado de dependencia semi-intensivo, querequiere atención continua e individualizada. Conclusión: La identificación y clasificación delos pacientes en función de su dependencia permitieron al equipo una mejor comprensión delas necesidades humanas básicas e hicieron posible la construcción de un plan de atención a laclientela

Cytokeratin-based CTC counting unrelated to clinical follow up.

BACKGROUND: Circulating tumor cells (CTCs) have been reported to be a relevant prognostic biomarker in metastatic patients. However, their clinical use and impact is still under debate. We have thus comparatively and kinetically assessed two CTC detection methods according to the patient's clinical follow up. METHODS: CTC counting and characterization were repeatedly performed during follow up in a patient with metastatic undifferentiated non-small cell lung cancer by using cytokeratin (CK)-dependent immunomagnetic separation (Miltenyi) and CK-independent, size-based isolation [isolation by size of tumor cells (ISET)] (Rarecells). RESULTS: Comparison between the two methods showed a parallel increase of CTC detected by ISET and worsening of the clinical status, while CK-dependent CTC numbers were decreasing, misleadingly suggesting a response to treatment. ISET results were in agreement with the clinical follow up showing Circulating tumor microemboli (CTM) and CTC expressing a mesenchymal marker with absence of epithelial markers. CONCLUSIONS: This case report study shows the interest of a comparative and kinetic analysis of different methods for CTCs detection combined with their evaluation according to the clinical follow up. Our results should open up an area for future research and validation in larger clinical cohorts.

Circulating tumor cells: basic concepts and some clinical applications

The spread of cancer requires the presence of circulating tumor cells (CTCs), which are rare cells surrounded by billions of normal hematopoietic cells in the bloodstream. It is believed thatCTCs tend to metastasize to certain organs, thus, their presence may determine invasive tumor behavior. Generally, these cells are undetectable by conventional histopathological analysisand imaging exams with high resolution. Therefore, more sensitive immunohistochemical and molecular assays have been developed that have allowed the specific detection of metastatic tumor cells in regional lymph nodes, peripheral blood and bone marrow. This article reviews theliterature regarding CTCs and tumors of the breast, colorectal, pancreas and lung as it pertains to forms of detection and clinicopathological correlations, in addition to future outlooks