Principais medidas tomadas para a mudança dos processos assistenciais durante a pandemia por COVID-19 / Main measures taken to change assistance processes during the pandemic by COVID-19

Objetivo: descrever as principais medidas tomadas para mudança dos processos assistenciais e de comunicação interna na vigência da pandemia por COVID-19 de um hospital oncológico. Método: Trata-se de um relato de experiência. Resultados: 1) Criação do fórum para tomadas de decisões assistenciais. 2) Criação do canal de dúvidas e centralização dos protocolos assistenciais e 3) Encontro semanais online. Considerações finais: O êxito e as conquista obtidas até o momento, se dão o trabalho em equipe, o alinhamento com uma linguagem única e a busca pelo os princípios guiados pela segurança do paciente, dos profissionais, acesso e qualidade da informação, através da busca de uma comunicação efetiva. (AU)

Objective: to describe the main measures adopted to change the care and internal communication processes in the pandemic surveillance by COVID-19 of an oncology hospital. Method: This is an experience report. Results: 1) Creation of a forum for assistance decision-making. 2) Creation of the channel of doubts and centralization of assistance protocols and 3) Weekly online meeting. Final considerations: Success and achievement so far, if the work is carried out as a team, alignment with a unique language and the search for principles guided by the safety of the patient, professionals, access and quality of information, by seeking effective communication. (AU)

Objetivo: describir las principales medidas tomadas para cambiar los procesos de atención y comunicación interna durante la pandemia COVID-19 de un hospital oncológico. Método: este es un informe de experiencia. Resultados: 1) Creación de un foro para la toma de decisiones de asistencia. 2) Creación del canal de dudas y centralización de protocolos de asistencia y 3) Reunión semanal en línea. Consideraciones finales: El éxito y los logros alcanzados hasta ahora se deben al trabajo en equipo, la alineación con un lenguaje único y la búsqueda de principios guiados por la seguridad del paciente, los profesionales, el acceso y la calidad de la información, a través de la búsqueda. comunicación efectiva. (AU)

EVALUATING MMP-2 AND TGFß-RI EXPRESSION IN CIRCULATING TUMOR CELLS OF PANCREATIC CANCER PATIENTS AND THEIR CORRELATION WITH CLINICAL EVOLUTION.

BACKGROUND: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. AIM: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). METHOD: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. RESULTS: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. CONCLUSION: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.

Evaluating mmp-2 and tgfß-ri expression in circulating tumor cells of pancreatic cancer patients and their correlation with clinical evolution / Avaliação da expressão de mmp-2 e tgfß-ri em células tumorais circulantes de pacientes com câncer de pâncreas e sua correlação com evolução clínica

ABSTRACT Background: Metastasis is common in the diagnosis of pancreatic cancer, and the presence of epithelial-mesenchymal transition markers in circulating tumor cells may suggest worse prognosis. Aim: To correlate the number of circulating tumor cells (CTCs) in the peripheral blood of patients with a locally advanced or metastatic pancreatic tumor and the protein expression involved in epithelial-mesenchymal transition (EMT) in CTCs with clinical characteristics, progression-free survival (PFS) and overall survival (OS). Method: This was a prospective study conducted using peripheral blood samples collected at three different times. CTCs were quantified by the ISET test and analyzed by immunocytochemistry. Proteins involved in EMT (vimentin, TGFß-RI and MMP2) were analyzed in all CTCs. Results: Twenty-one patients were included. Median CTCs detected were 22, 20 and 8 CTCs/8 ml blood at baseline, first and second follow-up, respectively. No statistically significant correlation was found in correlating the number of CTCs and the evaluated clinical characteristics, PFS, or OS. There was no difference in PFS and OS among the EMT markers in the groups with and without markers. Conclusion: CTC analysis was not relevant in this sample for comparing clinical findings, PFS and OS in patients with pancreatic cancer. However, marker analysis in CTCs could be useful for the MMP-2 and/or TGFß-RI expression, as observed by the separate PFS curve.

RESUMO Racional: A metástase é comum no diagnóstico de câncer de pâncreas; presença de marcadores de transição epitélio-mesenquimal nas células tumorais circulantes (CTCs) podem sugerir pior prognóstico. Objetivo: Correlacionar o número de CTCs no sangue periférico de pacientes com tumor de pâncreas localmente avançado ou metastático e expressão de proteínas envolvidas na transição epitélio-mesenquimal (TEM) nas CTCs com características clínicas, sobrevida livre de progressão (SLP) e global (SG). Método: Estudo prospectivo realizado por meio de coletas de sangue periférico em três tempos distintos. As CTCs foram quantificadas pelo sistema ISET e analisadas por imunocitoquímica. Proteínas envolvidas na TEM (vimentina, TGFß-RI e MMP2) foram analisadas em todas as CTCs. Resultados: Foram incluídos 21 pacientes. A mediana de CTCs detectadas foi de 22, 20 e 8 CTCs/8 ml de sangue no baseline, primeiro e segundo seguimentos, respectivamente. Na correlação entre número de CTCs e as características clínicas levantadas, SLP, SG não houve correlação estatisticamente significante. Nos marcadores de TEM não houve diferença de SLP e SG entre os grupos que apresentaram e não apresentaram marcação. Conclusão: As CTCs não se mostraram relevantes na comparação dos achados clínicos, SLP e SG em pacientes com câncer de pâncreas. No entretanto, pode ser que para a análise de marcador seja útil, como observado pelas curvas separadas de expressão de MMP-2 e TGFß-RI nas CTCs.

MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer.

Circulating tumor cells are important markers of tumor progression and can reflect tumor behavior in metastatic colorectal cancer (mCRC). Identification of proteins that confer resistance to treatment is an important step to predict response and better selection of treatment for patients. Multidrug resistance-associated protein 1 (MRP1) and Multidrug resistance-associated protein 4 (MRP4) play a role in irinotecan-resistance, and Excision Repair Cross-Complementation group 1 (ERCC1) expression can confer resistance to platinum compounds. Here, we included 34 patients with mCRC and most of them received FOLFIRI or FOLFOX chemotherapy (91.1%). CTCs were isolated by ISET(®) Technology and identified in 30 patients (88.2%), with a median of 2.0 CTCs/mL (0-31.0). We analyzed the immunocytochemical expression of MRP1, MRP4 and ERCC1 only in patients who had previously detectable CTCs, accordingly to treatment received (n = 19, 15 and 13 patients, respectively). Among patients treated with irinotecan-based chemotherapy, 4 out of 19 cases with MRP1 positive CTCs showed a worse progression free survival (PFS) in comparison to those with MRP1 negative CTCs (2.1 months vs. 9.1 months; p = 0.003). None of the other proteins studied in CTCs had significant association with PFS. We analyzed also histological sections of primary tumors and metastases by immunohistochemistry, and found no association with clinicopathological characteristics or with PFS. Our results show MRP1 as a potential biomarker of resistance to treatment with irinotecan when found in CTCs from mCRC patients. This is a small proof-of-principle study and these early findings need to be validated in a larger cohort of patients.

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.