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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-09032020-143134
Document
Author
Full name
Daniel José Szor
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2019
Supervisor
Committee
Júnior, Ulysses Ribeiro (President)
Malheiros, Carlos Alberto
Pajecki, Denis
Rodriguez, Tomás Navarro
Title in Portuguese
Avaliação da relação neutrófilo-linfócito como fator prognóstico em pacientes com câncer gástrico submetidos à gastrectomia potencialmente curativa
Keywords in Portuguese
Biomarcadores tumorais
Carcinogênese
Gastrectomia
Inflamação
Neoplasias gástricas
Prognóstico
Abstract in Portuguese
INTRODUÇÃO: o adenocarcinoma gástrico (AG) persiste com elevada prevalência mundial, apesar da queda progressiva nos casos diagnosticados nas últimas décadas. O principal pilar do tratamento é a ressecção cirúrgica com intuito curativo. A presença de diferentes prognósticos em pacientes de mesmo estádio indica que fatores não avaliados rotineiramente podem influenciar a sobrevida. Um desses fatores seriam os biomarcadores inflamatórios, sustentados pela ideia que inflamação e câncer são duas entidades intimamente relacionadas. A relação neutrófilo-linfócito (NLR) é um marcador inflamatório que reflete o status inflamatório sistêmico do paciente e que apresenta potencial para predição prognóstica. OBJETIVOS: avaliar a importância prognóstica do NLR em pacientes com AG submetidos à gastrectomia potencialmente curativa. Verificar a associação entre o NLR e características clínicas, laboratoriais e anatomopatológicas dos pacientes. MÉTODOS: Foram avaliados, de forma retrospectiva, 383 pacientes com AG submetidos à gastrectomia com intuito curativo. O NLR foi calculado pela divisão entre os neutrófilos e os linfócitos séricos, obtidos de amostras sanguíneas pré-operatórias. Estabeleceu-se o valor de corte do NLR por meio da curva de Lausen e os pacientes foram agrupados em grupos acima ou abaixo deste valor. RESULTADOS: a média e o valor de corte estabelecidos para o NLR foram de 2,53 e 2,44, respectivamente. Dividiram-se os pacientes em grupos de baixo NLR (236 pacientes, 61,6%) ou alto NLR (147 pacientes, 38,3%), de acordo com a comparação de seu valor com o valor de corte. O grupo de NLR alto associou-se a pacientes de idade mais avançada (p = 0,03), do sexo masculino (p < 0,001), com plaquetose (p = 0,015) e tumores mais profundos (p = 0,02). No seguimento, os pacientes com NLR mais elevado apresentaram menor sobrevida global (p = 0,047) e livre de doença (p = 0,045). Mais ainda, pacientes com mesmo estádio clínico e grau de invasão tumoral apresentaram pior prognóstico quando o NLR era elevado (p = 0,02 e p = 0,032, respectivamente). A análise multivariada identificou o NLR elevado (p = 0,048), a hipoalbuminemia (p = 0,019), os tumores mais invasivos (p = 0,006) e o acometimento linfonodal (p = 0,007) como fatores independentes de pior prognóstico para sobrevida global. CONCLUSÃO: o NLR de valor elevado é um fator independente de pior prognóstico, indicando menor sobrevida global em pacientes com câncer gástrico submetidos à gastrectomia com intuito curativo. Seus valores elevados associam-se com idade avançada, sexo masculino, plaquetose e tumores mais invasivos (pT3/pT4). Trata-se de marcador de baixo custo, obtido de forma simples e facilmente reprodutível
Title in English
eutrophil-lymphocyte ratio is associated with prognosis in patients who underwent potentially curative resection for gastric cancer
Keywords in English
Cancer biomarkers
Carcinogenesis
Gastrectomy
Inflammation
Prognosis
Stomach neoplasms
Abstract in English
INTRODUCTION: gastric adenocarcinoma (GA) persists with high worldwide prevalence, despite the progressive fall in cases diagnosed during the last decades. The main cornerstone of the treatment is surgical resection with curative intent. The presence of different prognosis for same stage disease patients indicates that factors not routinely evaluated may influence survival. One of those factors would be the inflammatory biomarkers, supported by the idea that inflammation and cancer are two intimately related entities. The neutrophil-lymphocyte ratio (NLR) is an inflammatory marker, which reflects the systemic inflammatory status of the patient and sets forth a potential for prognosis prediction. OBJECTIVES: to evaluate the prognosis relevance of NLR in patients with GA who underwent potentially curative gastrectomy. To verify the association between NLR and clinical, laboratory and anatomopathological characteristics of the patients. METHODS: 383 patients with GA who underwent gastrectomy were retrospectively evaluated. NLR was calculated by the division between serum neutrophils and lymphocytes, obtained from preoperative blood samples. The cutoff value was established through the Lausen curve and two groups, high and low, were established according to patient´s NLR value. RESULTS: the average rate and cutoff value established for NLR were of 2.53 and 2.44 respectively. The patients were divided in groups of low (236 patients, 61.6%) and high NLR (147 patients, 38.3%), according to the comparison of their value with the cutoff value. The high NLR group showed patients of an older age (p = 0.03), male gender (p < 0.001), with thrombocytosis (p = 0.015) and deeper tumors (p = 0.02). Subsequently, the patients with a higher NLR presented lower overall survival (p = 0.047) and disease-free survival (p = 0.045). Even more, patients in the same clinical stage and tumoral invasion grade presented a worse prognosis when NLR was high (p = 0.02 and p = 0.032, respectively). The multivariate analysis identified NLR (p = 0.048), hypoalbuminemia (p = 0.019), more invasive tumors (p = 0.006) and lymph node involvement (p = 0.007) as independent prognosis factors. CONCLUSION: high NLR is an independent factor for worse prognosis, indicating lower overall survival in patients with gastric cancer who underwent curative gastrectomy. Higher values correlates with older age, male gender, thrombocytosis and more invasive tumors (pT3/pT4). This is a low cost marker, obtained through a simple and replicable way
 
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Publishing Date
2020-03-09
 
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