THE ROLE OF IMMUNOINFLAMMATORY MARKERS IN THE PROGNOSIS AND RESECTABILITY OF PANCREATIC ADENOCARCINOMA.

BACKGROUND: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. AIM: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. METHODS: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. RESULTS: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). CONCLUSIONS: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

The role of immunoinflammatory markers in the prognosis and resectability of pancreatic adenocarcinoma / O papel dos marcadores imunoinflamatórios no prognóstico e ressecabilidade do adenocarcinoma pancreático

ABSTRACT Background: Pancreatic adenocarcinoma has a high mortality rate. A prognostic tool is essential for a better risk stratification. The neutrophil/lymphocyte ratio and adaptations and the platelet/lymphocyte ratio seem promising for this purpose. Aim: Evaluate the prognostic value of neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio, analyze the ideal cutoff values and investigate their utility in predicting resectability. Methods: Data were collected of patients with pancreatic adenocarcinoma in Hospital de Clínicas de Porto Alegre between 2003 and 2013. The studied ratios were determined by blood count collected at hospital admission and after two cycles of palliative chemotherapy. Results: Basal neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio did not have prognostic impact in survival (p=0.394, p=0.152, p=0.177 respectively). In subgroup analysis of patients submitted to palliative chemotherapy, neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio determined after two cycles of chemotherapy were prognostic for overall survival (p=0.003, p=0.009, p=0.001 respectively). The ideal cutoff values found were 4,11 for neutrophil/lymphocyte ratio (sensitivity 83%, specificity 75%), 2,8 for derived neutrophil/lymphocyte ratio (sensitivity 87%, specificity 62,5%) and 362 for platelet/lymphocyte ratio (sensitivity 91%, specificity 62,5%), Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were not able to predict resectability (p=0.88; p=0.99; p=0.64 respectively). Conclusions: Neutrophil/lymphocyte ratio, derived neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are useful as prognostic markers of overall survival in patients with pancreatic adenocarcinoma submitted to palliative chemotherapy. Its use as resectability predictor could not be demonstrated.

RESUMO Racional: O adenocarcinoma pancreático apresenta alta taxa de mortalidade. Uma ferramenta que possa predizer adequadamente o seu prognóstico é fundamental para melhor estratificação de risco. A razão neutrófilos/linfócitos e suas adaptações e a razão plaquetas/linfócitos tem se mostrado promissores para este fim. Objetivo: Avaliar o valor prognóstico das razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos, analisar os pontos de corte mais adequados e investigar sua utilidade como fator preditivo de ressecabilidade. Métodos: Foram coletados dados de pacientes com adenocarcinoma pancreático atendidos no Hospital de Clínicas de Porto Alegre entre 2003 e 2013. As razões estudadas foram determinadas com base nos hemogramas coletados na internação e após dois ciclos de quimioterapia paliativa. Resultados: As razões neutrófilos/linfócitos basal, neutrófilos/linfócitos derivada basal e plaquetas/linfócitos basal não tiveram impacto prognóstico na sobrevida (p=0,394, p=0,152, p=0,177 respectivamente). No subgrupo submetido a quimioterapia paliativa, as razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos após dois ciclos de tratamento mostraram-se fatores prognósticos para sobrevida global (p=0,003, p=0,009 e p=0,001 respectivamente). Os pontos de corte encontrados foram 4,11 para neutrófilos/linfócitos (sensibilidade 83% e especificidade 75%), 362 para plaquetas/linfócitos (sensibilidade 91% e especificidade 62,5%) e 2,8 para neutrófilos/linfócitos derivada (sensibilidade 87% e especificidade 62,5%). As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos não se mostraram estatisticamente significativas como preditores para ressecabilidade (p=0,88; p=0,99 e p=0,64 respectivamente). Conclusões: As razões neutrófilos/linfócitos, neutrófilos/linfócitos derivada e plaquetas/linfócitos são úteis como marcadores prognósticos de sobrevida global em pacientes com adenocarcinoma pancreático submetidos à quimioterapia paliativa. Seu uso como preditor de ressecabilidade não foi demonstrado.

Daily practice feasibility and effectiveness of treating long-standing rheumatoid arthritis to target with synthetic disease-modifying antirheumatic drugs: a prospective cohort study.

To prospectively study the daily practice feasibility and effectiveness of treat-to-target (T2T) strategy with synthetic drugs aiming to maintain and achieve disease remission or low activity based on DAS28 and CDAI in long-standing rheumatoid (RA) patients. Two hundred and forty-one consecutive RA patients from Hospital de Clínicas de Porto Alegre were followed for 14 (±5.3) months. At follow-up, patients were evaluated by a rheumatologist at least once every 3 to 4 months. Treatment was adjusted following a step-up strategy, based on the disease activity scores (DAS28 and CDAI), aiming at remission (<2.6 or <2.8, respectively) or at least low disease activity (<3.2 or <10). Patients were predominantly women (84.7 %), mean age 54.9 (±11.9) years with 11.1 (±7.4) years of disease duration. At visit 4, T2T intervention significantly reduced DAS28 (4.6 ± 1.6 vs. 4.0 ± 1.5; p < 0.005), CDAI [17.8 (8.2-28.7) vs. 12.6 (5.1-22.5); p < 0.001], and HAQ (1.5 ± 0.9 vs. 1.3 ± 0.8; p = 0.002). At the end of the study, compared to the baseline scores, more patients achieved remission by DAS28 (11.6 vs. 18.6 %; p < 0.001) and CDAI (8.1 vs. 13.6 %; p < 0.001) and also low disease activity by DAS28 (9.8 vs. 13.0 %; p < 0.001) and CDAI (23.9 vs. 28.4 %; p < 0.001). Both average doses of sulfasalazine and methotrexate at visit 4 were higher (1375 vs. 1621 mg, p = 0.024; and 14.5 vs. 16.5 mg, p < 0.001, respectively). More patients were on combination therapy at the end of the follow-up (48.2 vs. 52.3 %; p < 0.001). The implementation of T2T strategy in the treatment of RA was feasible and effective in this outpatient population. The optimization of synthetic DMARDs use with dose adjustments and combinations of drugs seemed to improve disease outcome regarding disease activity and functional status.