Prognostic significance of neutrophil–lymphocyte ratio in resectable pancreatic neuroendocrine tumors with special reference to tumor-associated macrophages

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Vol. 19; no. 6; pp. 897 - 902
• Main Authors: Harimoto, Norifumi, Hoshino, Kouki, Muranushi, Ryo, Hagiwara, Kei, Yamanaka, Takahiro, Ishii, Norihiro, Tsukagoshi, Mariko, Igarashi, Takamichi, Tanaka, Hiroshi, Watanabe, Akira, Kubo, Norio, Araki, Kenichirou, Hosouchi, Yasuo, Suzuki, Hideki, Arakawa, Kazuhisa, Hirai, Keitarou, Fukazawa, Takaharu, Ikota, Hayato, Shirabe, Ken
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.09.2019; Elsevier Limited
• Subjects: Adult; Aged; Biomarkers; Blood; Blood transfusions; Cancer; CD163 antigen; Disease-Free Survival; Female; Follow-Up Studies; Humans; Inflammation; Kaplan-Meier Estimate; Leukocyte Count; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Lymphocyte Count; Lymphocytes; Macrophages; Macrophages - pathology; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Multivariate analysis; Neoplasm Recurrence, Local; Neuroendocrine tumors; Neuroendocrine Tumors - blood; Neuroendocrine Tumors - surgery; Neutrophil-to-lymphocyte ratio; Neutrophils; Pancreas; Pancreatectomy; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - surgery; pancreatic neuroendocrine tumor; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk factors; Surgery; Systemic Inflammatory Response Syndrome - epidemiology; Systemic Inflammatory Response Syndrome - etiology; Treatment Outcome; Tumor-associated macrophage; Neutrophil-to-lymphocyte ratio; pancreatic neuroendocrine tumor; Tumor-associated macrophage
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1016/j.pan.2019.08.003

Recent studies have shown that the systemic inflammatory response induced by cancer leads to cancer progression. Neutrophil-to-lymphocyte ratio (NLR) is the most reliable marker to detect systemic inflammation. In this study, we investigated the significance of NLR in patients with well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. We retrospectively collected data for patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at six institutions. Clinicopathological factors, recurrence, and immunohistochemical staining of tumor-associated macrophages (TAMs) were analyzed in a total of 55 patients in this study. High NLR (>3.41) in patients was significantly associated with higher white blood cell count, higher Ki-67 index, higher mitotic count, higher grade, higher incidence of lymph node metastasis, higher incidence of lymphatic and neural invasion, massive blood loss, and a large number of CD163-expressing TAMs. Recurrence-free survival of patients with high NLR was significantly poorer than that of patients with low NLR. Multivariate analysis identified high NLR, NET Grade 2 (G2) or Grade 3 (G3), and synchronous hepatic resection as independent risk factors for recurrence after curative resection. NLR is a promising predictor of recurrence after pancreatectomy that needs to be further investigated and that accumulation of TAMs in the tumor could be one of the causes of NLR elevation.