Norifumi Harimoto1, Kouki Hoshino2, Ryo Muranushi2, Kei Hagiwara2, Takahiro Yamanaka2, Norihiro Ishii2, Mariko Tsukagoshi3, Takamichi Igarashi2, Hiroshi Tanaka2, Akira Watanabe2, Norio Kubo2, Kenichirou Araki2, Yasuo Hosouchi4, Hideki Suzuki5, Kazuhisa Arakawa6, Keitarou Hirai7, Takaharu Fukazawa8, Hayato Ikota9, Ken Shirabe2. 1. Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Japan. Electronic address: nharimotoh1@gunma-u.ac.jp. 2. Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Japan. 3. Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Japan; Department of Innovative Cancer Immunotherapy, Graduate School of Medicine, Gunma University, Japan. 4. Department of Surgery, Gunma Saiseikai Maebashi Hospital, Japan. 5. Department of Surgery, Isesaki Municipal Hospital, Japan. 6. Department of Surgery, Japanese Red Cross Maebashi Hospital, Japan. 7. Department of Gastroenterological Surgery, Takasaki General Medical Center, Japan. 8. Department of Surgery, Gunma Chuo Hospital, Maebashi, Japan. 9. Department of Human Pathology, Graduate School of Medicine, Gunma University, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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