International Journal of Clinical Oncology

, Volume 22, Issue 4, pp 734–739 | Cite as

Neutrophil-to-lymphocyte ratio predicts metachronous liver metastasis of pancreatic neuroendocrine tumors

  • Kota Arima
  • Hirohisa Okabe
  • Daisuke Hashimoto
  • Akira Chikamoto
  • Hidetoshi Nitta
  • Takaaki Higashi
  • Takayoshi Kaida
  • Kensuke Yamamura
  • Yuki Kitano
  • Yoshihiro Komohara
  • Yo-ichi Yamashita
  • Toru Beppu
  • Motohiro Takeya
  • Hideo Baba
Original Article
  • 243 Downloads

Abstract

Background

Pancreatic neuroendocrine tumors (PNETs) are clinically malignant, having metastatic potential. Histological tumor grade is an accepted indicator of malignant potential, but noninvasive prognostic markers have not yet been identified. This study assessed whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict clinical outcomes of PNET patients.

Methods

Fifty-eight patients who underwent curative resection for PNETs between 2001 and 2015 were retrospectively evaluated. The correlations between the preoperative NLR and clinicopathological parameters, including patient baseline clinical characteristics, tumor progression, and postoperative oncological outcome were evaluated.

Results

A high preoperative NLR was significantly associated with large tumor size (P = 0.0015) and high tumor grade (P < 0.0001). Overall survival and relapse-free survival of patients with a high NLR (≥2.4) were significantly shorter than those of patients with a low NLR (<2.4, P = 0.0481 and P < 0.0001, respectively). Multivariate analysis revealed that NLR ≥2.4 and tumor size ≥2 cm were independent predictors of postoperative recurrence (hazard ratio 6.012, P = 0.0035 and 6.760, P = 0.0049, respectively). Interestingly, a high NLR independently predicted postoperative liver, but not lymph node, metastasis.

Conclusions

In this patient series, a high NLR (≥2.4) was a noninvasive marker that independently predicted postoperative liver metastasis in patients with PNETs, and thereby could be clinically useful.

Keywords

Pancreatic neuroendocrine tumor WHO grade Neutrophil-to-lymphocyte ratio Postoperative metachronous liver metastasis 

References

  1. 1.
    Fesinmeyer MD, Austin MA, Li CI et al (2005) Differences in survival by histologic type of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 14:1766–1773CrossRefPubMedGoogle Scholar
  2. 2.
    Yao JC, Eisner MP, Leary C et al (2007) Population-based study of islet cell carcinoma. Ann Surg Oncol 14:3492–3500CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Metz DC, Jensen RT (2008) Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology 135:1469–1492CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ito T, Sasano H, Tanaka M et al (2010) Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol 45:234–243CrossRefPubMedGoogle Scholar
  5. 5.
    Klimstra D, Arnold R, Capella C (2010) Neuroendocrine neoplasms of the pancreas. In: Brosman FT, Carneiro F, Hruban RH, Theise ND (eds) WHO classification of tumours of the digestive system, 4th edn. International Agency for Research on Cancer, Lyon, p 322–326Google Scholar
  6. 6.
    Toumpanakis CG, Caplin ME (2008) Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Am J Gastroenterol 103:729–732CrossRefPubMedGoogle Scholar
  7. 7.
    Bilimoria KY, Bentrem DJ, Merkow RP et al (2007) Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg 205:558–563CrossRefPubMedGoogle Scholar
  8. 8.
    Ehehalt F, Saeger HD, Schmidt CM et al (2009) Neuroendocrine tumors of the pancreas. Oncologist 14:456–467CrossRefPubMedGoogle Scholar
  9. 9.
    Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Raymond E, Dahan L, Raoul JL et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513CrossRefPubMedGoogle Scholar
  11. 11.
    Ito T, Lee L, Hijioka M et al (2015) The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan. J Hepatobiliary Pancreat Sci 22:574–577CrossRefPubMedGoogle Scholar
  12. 12.
    Capurso G, Bettini R, Rinzivillo M et al (2011) Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review. Neuroendocrinology 93:223–229CrossRefPubMedGoogle Scholar
  13. 13.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545CrossRefPubMedGoogle Scholar
  14. 14.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Proctor MJ, Talwar D, Balmar SM et al (2010) The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow inflammation outcome study. Br J Cancer 103:870–876CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Proctor MJ, Morrison DS, Talwar D et al (2011) A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow inflammation outcome study. Eur J Cancer 47:2633–2641CrossRefPubMedGoogle Scholar
  17. 17.
    Gomez D, Morris-Stiff G, Toogood GJ et al (2008) Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma. J Surg Oncol 97:513–518CrossRefPubMedGoogle Scholar
  18. 18.
    Zahorec R (2001) Ratio of neutrophil to lymphocyte counts—rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102:5–14PubMedGoogle Scholar
  19. 19.
    Paramanathan A, Saxena A, Morris DL (2014) A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol 23:31–39CrossRefPubMedGoogle Scholar
  20. 20.
    Mano Y, Shirabe K, Yamashita Y et al (2013) Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg 258:301–305CrossRefPubMedGoogle Scholar
  21. 21.
    Motomura T, Shirabe K, Mano Y et al (2013) Neutrophil–lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol 58:58–64CrossRefPubMedGoogle Scholar
  22. 22.
    Sugiura T, Uesaka K, Kanemoto H et al (2013) Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of survival after gastroenterostomy in patients with advanced pancreatic adenocarcinoma. Ann Surg Oncol 20:4330–4337CrossRefPubMedGoogle Scholar
  23. 23.
    Kishi Y, Kopetz S, Chun YS et al (2009) Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol 16:614–622CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang X, Zhang W, Feng LJ (2014) Prognostic significance of neutrophil lymphocyte ratio in patients with gastric cancer: a meta-analysis. PLoS One 9:e111906CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Arima K, Okabe H, Hashimoto D et al (2015) The neutrophil-to-lymphocyte ratio predicts malignant potential in intraductal papillary mucinous neoplasms. J Gastrointest Surg 19:2171–2177CrossRefPubMedGoogle Scholar
  26. 26.
    Poultsides GA, Huang LC, Cameron JL et al (2012) Duodenal adenocarcinoma: clinicopathologic analysis and implications for treatment. Ann Surg Oncol 19:1928–1935CrossRefPubMedGoogle Scholar
  27. 27.
    National Comprehensive Cancer Network Panel Members. Neuroendocrine tumors. NCCN practice guidelines in oncology. v.2.2014 (2014)Google Scholar
  28. 28.
    Arima K, Okabe H, Hashimoto D et al (2016) The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting pancreatic ductal adenocarcinoma in patients with pancreatic diseases. Int J Clin Oncol 21(5):940–945CrossRefPubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Kota Arima
    • 1
  • Hirohisa Okabe
    • 1
  • Daisuke Hashimoto
    • 1
  • Akira Chikamoto
    • 1
  • Hidetoshi Nitta
    • 1
  • Takaaki Higashi
    • 1
  • Takayoshi Kaida
    • 1
  • Kensuke Yamamura
    • 1
  • Yuki Kitano
    • 1
  • Yoshihiro Komohara
    • 2
  • Yo-ichi Yamashita
    • 1
  • Toru Beppu
    • 1
  • Motohiro Takeya
    • 2
  • Hideo Baba
    • 1
  1. 1.Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Department of Cell Pathology, Graduate School of Medical SciencesKumamoto University HospitalKumamotoJapan

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