Advertisement

Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer

  • Tamuro HayamaEmail author
  • Yojiro Hashiguchi
  • Yuka Okada
  • Kohei Ono
  • Kentaro Nemoto
  • Ryu Shimada
  • Tsuyoshi Ozawa
  • Tetsutaka Toyoda
  • Takeshi Tsuchiya
  • Hisae Iinuma
  • Keijiro Nozawa
  • Keiji Matsuda
Original Article
  • 20 Downloads

Abstract

Purpose

High neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. Preoperative NLR in colorectal cancer reportedly correlates with recurrence-free survival and is useful as a recurrence prediction factor. No reports have yet investigated recurrence factors using postoperative NLR. This study assessed the predictive value of NLR preoperatively and on the first (NLR1) and seventh day (NLR7) postoperatively in patients with stage II colorectal cancer.

Methods

We performed a retrospective cohort study involving patients undergoing colorectal resection at a single institution between January 2012 and December 2016; we used medical records of 176 consecutive patients with stage II colorectal cancer undergoing curative tumor resection. NLRs as well as clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with recurrence-free survival (RFS).

Results

Univariate analysis revealed that elevated NLR, NLR7, and lymphatic invasion were significantly associated with decreased RFS (p < 0.05). NLR7 was revealed as significant via multivariate analysis (p = 0.013). The 3-year RFS rate was 87.1% for patients with normal NLR7 and 70.3% for those with elevated NLR7.

Conclusion

Elevated seventh-day postoperative NLR is a significant independent predictor of reduced RFS for patients with stage II colorectal cancer and may be a potential biomarker for identifying candidates for adjuvant chemotherapy.

Keywords

Neutrophil-to-lymphocyte ratio Stage II colorectal cancer Curative tumor resection Recurrence-free survival 

Notes

References

  1. 1.
    Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi REM, Corcione F (2016) Worldwide burden of colorectal cancer: a review. Updat Surg 68:7–11.  https://doi.org/10.1007/s13304-016-0359-y CrossRefGoogle Scholar
  2. 2.
    Halazun KJ, Aldoori A, Malik HZ, Al-Mukhtar A, Prasad KR, Toogood GJ, Lodge JP (2008) Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol 34:55–60.  https://doi.org/10.1016/j.ejso.2007.02.014 CrossRefPubMedGoogle Scholar
  3. 3.
    Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN (2009) Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol 16:614–622.  https://doi.org/10.1245/s10434-008-0267-6 CrossRefPubMedGoogle Scholar
  4. 4.
    Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, Chen J, Liu X, Wang SK (2014) The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 31:305.  https://doi.org/10.1007/s12032-014-0305-0 CrossRefPubMedGoogle Scholar
  5. 5.
    Kao SC, Pavlakis N, Harvie R, Vardy JL, Boyer MJ, van Zandwijk N, Clarke SJ (2010) High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy. Clin Cancer Res 16:5805–5813.  https://doi.org/10.1158/1078-0432.CCR-10-2245 CrossRefPubMedGoogle Scholar
  6. 6.
    Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T (2013) Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol 23:265–273.  https://doi.org/10.3802/jgo.2012.23.4.265 CrossRefGoogle Scholar
  7. 7.
    Szkandera J, Gerger A, Liegl-Atzwanger B, Absenger G, Stotz M, Friesenbichler J, Trajanoski S, Stojakovic T, Eberhard K, Leithner A, Pichler M (2014) The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas. Int J Cancer 135:362–370.  https://doi.org/10.1002/ijc.28677 CrossRefPubMedGoogle Scholar
  8. 8.
    Absenger G, Szkandera J, Pichler M, Stotz M, Arminger F, Weissmueller M, Schaberl-Moser R, Samonigg H, Stojakovic T, Gerger A (2013) A derived neutrophil to lymphocyte ratio predicts clinical outcome in stage II and III colon cancer patients. Br J Cancer 109:395–400.  https://doi.org/10.1038/bjc.2013.346 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ulich TR, del Castillo J, Keys M, Granger GA, Ni RX (1987) Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosisfactor-alpha- induced changes in circulating numbers of neutrophils and lymphocytes. J Immunol 139:3406–3415PubMedGoogle Scholar
  10. 10.
    Ulich TR, del Castillo J, Guo KZ (1989) In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood 73:108–110CrossRefGoogle Scholar
  11. 11.
    Teramukai S, Kitano T, Kishida Y, Kawahara M, Kubota K, Komuta K, Minato K, Mio T, Fujita Y, Yonei T, Nakano K (2009) Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer 45:1950–1958.  https://doi.org/10.1016/j.ejca.2009.01.023 CrossRefPubMedGoogle Scholar
  12. 12.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867.  https://doi.org/10.1038/nature01322 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cedrés S, Torrejon D, Martínez A, Martinez P, Navarro A, Zamora E, Mulet-Margalef N, Felip E (2012) Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer. Clin Transl Oncol 14:864–869.  https://doi.org/10.1007/s12094-012-0872-5 CrossRefPubMedGoogle Scholar
  14. 14.
    The American Joint Committee on Cancer (2018) AJCC cancer staging manual. Springer-Verlag, New YorkGoogle Scholar
  15. 15.
    Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP (2011) Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg 35:868–872.  https://doi.org/10.1007/s00268-011-0984-z CrossRefPubMedGoogle Scholar
  16. 16.
    Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E (2009) Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg 137:425–428.  https://doi.org/10.1016/j.jtcvs.2008.05.046 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y, Fukushima M (2007) The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology 73:215–220.  https://doi.org/10.1159/000127412 CrossRefPubMedGoogle Scholar
  18. 18.
    Terzic J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138:2101–2114.  https://doi.org/10.1053/j.gastro.2010.01.058 CrossRefPubMedGoogle Scholar
  19. 19.
    Lin EY, Pollard JW (2004) Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer 90:2053–2058.  https://doi.org/10.1038/sj.bjc.6601705 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ (2010) Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 15:516–522.  https://doi.org/10.3109/1354750X.2010.491557 CrossRefPubMedGoogle Scholar
  21. 21.
    Petrie HT, Klassen LW, Kay HD (1985) Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J Immunol 134:230–234PubMedGoogle Scholar
  22. 22.
    El-Hag A, Clark RA (1987) Immunosuppression by activated human neutrophils. Dependence on the myeloperoxidase system. J Immunol 139:2406–2413PubMedGoogle Scholar
  23. 23.
    Dell’Aquila E, Cremolini C, Zeppola T, Lonardi S, Bergamo F, Masi G, Stellato M, Marmorino F, Schirripa M, Urbano F, Ronzoni M (2018) Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO. Ann Oncol 29:924–930.  https://doi.org/10.1093/annonc/mdy004 CrossRefPubMedGoogle Scholar
  24. 24.
    Sue K (2017) The science behind “man flu”. BMJ 359:j5560.  https://doi.org/10.1136/bmj.j5560 CrossRefPubMedGoogle Scholar
  25. 25.
    Shimada H, Fukagawa T, Haga Y, Oba K (2017) Does postoperative morbidity worsen the oncological outcome after radical surgery for gastrointestinal cancers? A systematic review of the literature. Ann Gastroenterol Surg 1:11–23.  https://doi.org/10.1002/ags3.12002 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Xia X, Wu W, Zhang K, Cen G, Jiang T, Cao J, Huang K, Huang C, Qiu Z (2014) Prognostic significance of complications after laparoscopic colectomy for colon cancer. PLoS One 9:e108348.  https://doi.org/10.1371/journal.pone.0108348 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Park EJ, Baik SH, Kang J, Hur H, Min BS, Lee KY, Kim NK (2016) The impact of postoperative complications on long-term oncologic outcomes after laparoscopic low anterior resection for rectal cancer. Medicine 95:e3271.  https://doi.org/10.1097/MD.0000000000003271 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ibuki Y, Hamai Y, Emi M, Taomoto J, Frukawa T, Yamakita I, Kurosawa T, Okada M (2017) Role of postoperative C-reactive protein levels in predicting prognosis after surgical treatment of esophageal cancer. World journal of Surgical oncology 41(6):1558–1565.  https://doi.org/10.1007/s00268-017-3900-3 CrossRefGoogle Scholar
  29. 29.
    Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, Lesser M, Widmann WD (2011) Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 11:445–452.  https://doi.org/10.1159/000331494 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Tamuro Hayama
    • 1
    Email author
  • Yojiro Hashiguchi
    • 1
  • Yuka Okada
    • 1
  • Kohei Ono
    • 1
  • Kentaro Nemoto
    • 1
  • Ryu Shimada
    • 1
  • Tsuyoshi Ozawa
    • 1
  • Tetsutaka Toyoda
    • 2
  • Takeshi Tsuchiya
    • 1
  • Hisae Iinuma
    • 1
  • Keijiro Nozawa
    • 1
  • Keiji Matsuda
    • 1
  1. 1.Department of SurgeryTeikyo University School of MedicineTokyoJapan
  2. 2.Department of SurgeryNippon Medical SchoolTokyoJapan

Personalised recommendations