Immune cells and checkpoints in pancreatic adenocarcinoma: Association with clinical and pathological characteristics.

INTRODUCTION: Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. METHODS: Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. RESULTS: CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. CONCLUSIONS: PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.

METACHRONOUS COLORECTAL LIVER METASTASES HAS BETTER PROGNOSIS - IS IT TRUE?

BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

Metástase hepática colorretal metacrônica tem melhor prognóstico - é verdade? / Metachronous colorectal liver metastases has better prognosis - is it true?

ABSTRACT BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

RESUMO CONTEXTO: As metástases hepáticas de câncer colorretal representam um importante problema de saúde pública devido à incidência crescente de câncer colorretal pelo mundo. A metástase hepática colorretal sincrônica está associada a pior sobrevida, no entanto, o pior prognóstico é assunto controverso. OBJETIVO: O objetivo do estudo foi avaliar a sobrevida livre de recorrência e a sobrevida global entre os grupos de pacientes com metástase hepática colorretal metacrônica e sincrônica. MÉTODO: Análise retrospectiva através de revisão de prontuários de pacientes com metástase hepática colorretal atendidos no período de 2013 a 2016, divididos em grupos metacrônico e sincrônico. Foram utilizados o modelo de regressão de Cox e o método de Kaplan-Meier com teste de Log-rank para comparação de sobrevida entre os grupos. RESULTADOS: A média de sobrevida livre de recorrência no grupo metacrônico foi de 9,75 meses e 50% em 1 ano, e no grupo sincrônico 19,73 meses e 63,3% em 1 ano. A média de sobrevida global no grupo metacrônico foi de 20,00 meses e 6,2% em 3 anos, e no grupo sincrônico 30,39 meses e 31,6% em 3 anos. Os pacientes com metástase hepática metacrônica apresentaram pior sobrevida global em análise multivariada. O uso de drogas biológicas associadas ao tratamento quimioterápico foi relacionado ao melhor prognóstico em sobrevida global. CONCLUSÃO: A metástase hepática colorretal metacrônica foi associada a pior prognóstico na sobrevida global. Não houve diferença na sobrevida livre de recorrência entre as metástases metacrônica e sincrônica.

The feasibility of an experimental model of donors after cardiac death in remote ischemic preconditioning studies for renal transplantation in porcine.

PURPOSE: To evaluate the feasibility of an experimental model of donors after cardiac death in remote ischemic preconditioning studies. METHODS: Twelve Landrace pigs were used as organ donors. They underwent cardiac arrest by coronary en block suture and interruption of ventilatory support. Haemodynamic data regarding the donor surgical protocol were evaluated. Studies variables included mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central venous pressure and oxygen saturation and the time to death. RESULTS: Haemodynamic parameter indicated that the circulatory failure occurred after nine minutes of en block coronary suture and respiratory support interruption. The circulatory collapse occurred evenly across all groups. The heart rate and central venous pressure were statistically different between groups (p=0.023 and p=0.04), respectively. The remote preconditioning resulted in delayed time of death. CONCLUSIONS: The model is feasible, and was easily reproduced. The ischemic remote preconditioning tends to a slight increase in circulatory failure time.

The feasibility of an experimental model of donors after cardiac death in remote ischemic preconditioning studies for renal transplantation in porcine

To evaluate the feasibility of an experimental model of donors after cardiac death in remote ischemic preconditioning studies. METHODS: Twelve Landrace pigs were used as organ donors. They underwent cardiac arrest by coronary en block suture and interruption of ventilatory support. Haemodynamic data regarding the donor surgical protocol were evaluated. Studies variables included mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, central venous pressure and oxygen saturation and the time to death. RESULTS: Haemodynamic parameter indicated that the circulatory failure occurred after nine minutes of en block coronary suture and respiratory support interruption. The circulatory collapse occurred evenly across all groups. The heart rate and central venous pressure were statistically different between groups (p=0.023 and p=0.04), respectively. The remote preconditioning resulted in delayed time of death. CONCLUSIONS: The model is feasible, and was easily reproduced. The ischemic remote preconditioning tends to a slight increase in circulatory failure time.

Non heart beating organ donor: new experimental model in pigs.

PURPOSE: To describe technical aspects of a new experimental model that simulates a non heart beating organ donor. METHODS: Landrace pigs were operated on and cardiac arrest was obtained by means of myocardial infarction and interruption of ventilator support. RESULTS: Mean cardiac frequency, systolic and diastolic blood pressure levels, central venous pressure, oxygen saturation and concentration of expired CO(2) dropout occurred at seven minutes after cardiac arrest. CONCLUSION: The procedure was easily reproduced and a homogeneous circulatory failure could de obtained by the end of seven minutes. The model is suitable for further studies regarding abdominal organ transplantation.

Non heart beating organ donor: new experimental model in pigs / Doador de coração parado: novo modelo experimental em suínos

PURPOSE: To describe technical aspects of a new experimental model that simulates a non heart beating organ donor. METHODS: Landrace pigs were operated on and cardiac arrest was obtained by means of myocardial infarction and interruption of ventilator support. RESULTS: Mean cardiac frequency, systolic and diastolic blood pressure levels, central venous pressure, oxygen saturation and concentration of expired CO2 dropout occurred at seven minutes after cardiac arrest. CONCLUSION: The procedure was easily reproduced and a homogeneous circulatory failure could de obtained by the end of seven minutes. The model is suitable for further studies regarding abdominal organ transplantation.

OBJETIVO: Descrever os aspectos técnicos de um novo modelo experimental que simula um doador de órgãos após a parada cardíaca. MÉTODOS: Suínos da raça Landrace foram operados e a parada cardíaca foi obtida por meio de infarto do miocárdio e interrupção do suporte ventilatório. RESULTADOS: Freqüência cardíaca, pressão arterial sistólica e diastólica, pressão venosa central, saturação de oxigênio e concentração parcial de CO2 são consistentes com falência hemodinâmica ao final de sete minutos. CONCLUSÕES: O procedimento foi facilmente executado e uma falência circulatória pode ser obtida ao final de sete minutos. Este modelo é adequado para estudos posteriores com respeito a preservação e tranplantes de órgãos abdominais.