Skip to main content

Advertisement

SpringerLink
Log in

Modified neutrophil-platelet score as a promising marker for stratified surgical and oncological outcomes of patients with gastric cancer

  • Original Article
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

Purpose

Gastric cancer (GC) is a common malignancy, especially in East Asian countries. There is emerging evidence that circulating neutrophil and platelet levels correlate with cancer progression. We evaluated the short- and long-term outcomes of GC patients systemically, to compare the original neutrophil–platelet score (NPS) and our modified NPS (mNPS).

Methods

We analyzed the original pre-operative NPS and the mNPS of 621 GC patients.

Results

Racial differences between the United Kingdom and East Asian countries accounted for compelling deviation in classification using the original NPS, which could not reliably stratify the prognoses of Japanese GC patients. We developed the mNPS using appropriate cutoff levels for pre-operative neutrophils and platelets, and demonstrated that the pre-operative mNPS was significantly correlated with all of the well-established clinicopathological factors for disease development, including advanced T stage, venous and lymphatic vessel invasion, lymph node/peritoneal /distant metastasis, and tumor-node-metastasis stage. The pre-operative mNPS could stratify prognostication for both overall survival (OS) and disease-free survival (DFS): a high pre-operative mNPS was an independent prognostic factor for the OS and DFS of GC patients and also an independent predictor of post-operative surgical site infection after gastrectomy.

Conclusion

Calculating the mNPS could help clinicians to stratify the surgical and oncological risks of patients with GC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics. 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386386.

    Article  CAS  PubMed  Google Scholar 

  3. Andre N, Schmiegel W. Chemoradiotherapy for colorectal cancer. Gut. 2005;54(8):1194–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lurje G, Zhang W, Lenz HJ. Molecular prognostic markers in locally advanced colon cancer. Clin Colorectal Cancer. 2007;6(10):683–90.

    Article  CAS  PubMed  Google Scholar 

  5. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

    Article  CAS  Google Scholar 

  6. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet (Lond Engl). 2001;357(9255):539–45.

    Article  CAS  Google Scholar 

  7. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81.

    Article  CAS  PubMed  Google Scholar 

  8. Mohri Y, Tanaka K, Toiyama Y, Ohi M, Yasuda H, Inoue Y, et al. Impact of preoperative neutrophil to lymphocyte ratio and postoperative infectious complications on survival after curative gastrectomy for gastric cancer: a single institutional cohort study. Medicine. 2016;95(11):e3125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Toiyama Y, Shimura T, Yasuda H, Fujikawa H, Okita Y, Kobayashi M, et al. Clinical burden of C-reactive protein/albumin ratio before curative surgery for patients with gastric cancer. Anticancer Res. 2016;36(12):6491–8.

    Article  CAS  PubMed  Google Scholar 

  10. Ide S, Toiyama Y, Okugawa Y, Oki S, Yasuda H, Fujikawa H, et al. Clinical significance of C-reactive protein-to-albumin ratio with rectal cancer patient undergoing chemoradiotherapy followed by surgery. Anticancer Res. 2017;37(10):5797–804.

    CAS  PubMed  Google Scholar 

  11. Okugawa Y, Toiyama Y, Oki S, Ide S, Yamamoto A, Ichikawa T, et al. Feasibility of assessing prognostic nutrition index in patients with rectal cancer who receive preoperative chemoradiotherapy. JPEN J Parenter Enteral Nutr. 2018;42(6):998–1007.

    Article  CAS  PubMed  Google Scholar 

  12. Okugawa Y, Shirai Y, Toiyama Y, Saigusa S, Hishida A, Yokoe T, et al. Clinical burden of modified glasgow prognostic scale in colorectal cancer. Anticancer Res. 2018;38(3):1599–610.

    CAS  PubMed  Google Scholar 

  13. Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, et al. Neutrophils scan for activated platelets to initiate inflammation. Science (NY NY). 2014;346(6214):1234–8.

    Article  CAS  Google Scholar 

  14. Watt DG, Proctor MJ, Park JH, Horgan PG, McMillan DC. The neutrophil-platelet score (NPS) predicts survival in primary operable colorectal cancer and a variety of common cancers. PLoS ONE. 2015;10(11):e0142159.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Koike Y, Miki C, Okugawa Y, Yokoe T, Toiyama Y, Tanaka K, et al. Preoperative C-reactive protein as a prognostic and therapeutic marker for colorectal cancer. J Surg Oncol. 2008;98(7):540–4.

    Article  CAS  PubMed  Google Scholar 

  16. Shirai Y, Okugawa Y, Hishida A, Ogawa A, Okamoto K, Shintani M, et al. Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia. Sci Rep. 2017;7(1):4826.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Oki S, Toiyama Y, Okugawa Y, Shimura T, Okigami M, Yasuda H, et al. Clinical burden of preoperative albumin-globulin ratio in esophageal cancer patients. Am J Surg. 2017;214(5):891–8.

    Article  PubMed  Google Scholar 

  18. Fujikawa H, Toiyama Y, Inoue Y, Imaoka H, Shimura T, Okigami M, et al. Prognostic impact of preoperative albumin-to-globulin ratio in patients with colon cancer undergoing surgery with curative intent. Anticancer Res. 2017;37(3):1335–422.

    Article  CAS  PubMed  Google Scholar 

  19. Shimura T, Toiyama Y, Saigusa S, Imaoka H, Okigami M, Fujikawa H, et al. Inflammation-based prognostic scores as indicators to select candidates for primary site resection followed by multimodal therapy among colorectal cancer patients with multiple metastases. Int J Clin Oncol. 2017;22(4):758–66.

    Article  PubMed  Google Scholar 

  20. Mori K, Toiyama Y, Saigusa S, Fujikawa H, Hiro J, Kobayashi M, et al. Systemic analysis of predictive biomarkers for recurrence in colorectal cancer patients treated with curative surgery. Dig Dis Sci. 2015;60(8):2477–87.

    Article  CAS  PubMed  Google Scholar 

  21. Shaul ME, Fridlender ZG. Cancer related circulating and tumor-associated neutrophils—subtypes, sources and function. FEBS J. 2018.

  22. Schmidt H, Bastholt L, Geertsen P, Christensen IJ, Larsen S, Gehl J, et al. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer. 2005;93(3):273–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lechner MG, Liebertz DJ, Epstein AL. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol (Baltimore, Md : 1950). 2010;185(4):2273–84.

    Article  CAS  Google Scholar 

  24. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Demers M, Wagner DD. NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost. 2014;40(3):277–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA. 2012;109(32):13076–81.

    Article  CAS  PubMed  Google Scholar 

  27. Bystricky B, Reuben JM, Mego M. Circulating tumor cells and coagulation-minireview. Crit Rev Oncol Hematol. 2017;114:33–42.

    Article  PubMed  Google Scholar 

  28. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science (NY, NY). 2004;303(5663):1532–5.

    Article  CAS  Google Scholar 

  29. Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S, Giannias B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Investig. 2013.

  30. Naschitz JE, Yeshurun D, Eldar S, Lev LM. Diagnosis of cancer-associated vascular disorders. Cancer. 1996;77(9):1759–67.

    Article  CAS  PubMed  Google Scholar 

  31. Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Kubota K. Preoperative thrombocytosis is associated with survival after surgery for colorectal cancer. J Surg Oncol. 2012;106(7):887–91.

    Article  PubMed  Google Scholar 

  32. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. 2014;123(18):2768–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Watt DG, Martin JC, Park JH, Horgan PG, McMillan DC. Neutrophil count is the most important prognostic component of the differential white cell count in patients undergoing elective surgery for colorectal cancer. Am J Surg. 2015;210(1):24–30.

    Article  PubMed  Google Scholar 

  34. Leitch EF, Chakrabarti M, Crozier JE, McKee RF, Anderson JH, Horgan PG, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007;97(9):1266–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W, et al. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol. 2005;46(3):464–9.

    Article  CAS  PubMed  Google Scholar 

  36. Yamada S, Gotoh T, Nakashima Y, Kayaba K, Ishikawa S, Nago N, et al. Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population: Jichi Medical School Cohort Study. Am J Epidemiol. 2001;153(12):1183–90.

    Article  CAS  PubMed  Google Scholar 

  37. Lakoski SG, Cushman M, Palmas W, Blumenthal R, D'Agostino RB Jr, Herrington DM. The relationship between blood pressure and C-reactive protein in the multi-ethnic study of atherosclerosis (MESA). J Am Coll Cardiol. 2005;46(10):1869–74.

    Article  CAS  PubMed  Google Scholar 

  38. McDade TW, Rutherford JN, Adair L, Kuzawa C. Population differences in associations between C-reactive protein concentration and adiposity: comparison of young adults in the Philippines and the United States. Am J Clin Nutr. 2009;89(4):1237–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Moyes LH, Leitch EF, McKee RF, Anderson JH, Horgan PG, McMillan DC. Preoperative systemic inflammation predicts postoperative infectious complications in patients undergoing curative resection for colorectal cancer. Br J Cancer. 2009;100(8):1236–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Canna K, McArdle PA, McMillan DC, McNicol AM, Smith GW, McKee RF, et al. The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer. 2005;92(4):651–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by a research grant from Japanese Society for Palliative Medicine and Mie Medical Research Foundation.

Author information

Authors and Affiliations

  1. Division of Reparative Medicine, Institute of Life Sciences, Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Yoshinaga Okugawa, Yuji Toiyama, Akira Yamamoto, Yusuke Omura, Kurando Kusunoki, Chengzeng Yin, Shozo Ide, Takahito Kitajima, Yuki Koike, Hiroyuki Fujikawa, Hiromi Yasuda, Yoshiki Okita, Junichiro Hiro, Shigeyuki Yoshiyama, Masaki Ohi, Toshimitsu Araki & Masato Kusunoki

Authors
  1. Yoshinaga Okugawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuji Toiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusuke Omura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kurando Kusunoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chengzeng Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shozo Ide
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Takahito Kitajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuki Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hiroyuki Fujikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiromi Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoshiki Okita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Junichiro Hiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Shigeyuki Yoshiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masaki Ohi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Toshimitsu Araki
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Masato Kusunoki
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study concept and design: YO, YT, MO, KM; provision of samples: AY, YO, KK, CY, SI, TK, HF, HY, JH, SY, MO, TA; acquisition of data: YO, YT, AY, YO, KK, CY, SI, TK, YK, HF, HY, JH, SY, MO, TA; analysis and interpretation of data: YO, YT, MO, TA; statistical analysis: YO, YT; and drafting of the manuscript: YO, YT, MO, MK.

Corresponding authors

Correspondence to Yoshinaga Okugawa or Yuji Toiyama.

Ethics declarations

Conflict of interests

We have no conflict of interest to disclose for this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 23 kb)

595_2019_1873_MOESM2_ESM.tif

Supplementary Fig. 1. Prognostic impact of the modified NPS status divided by stage classification for the overall survival (OS) and disease-free survival (DFS) of patients with gastric cancer (GC). Although prognostic stratification of the mNPS was not significantly different in the population with Stage I or Stage II/III disease, its impact was revealed more clearly in Stage IV GC patients (P=0.04, log rank test) (TIFF 797 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okugawa, Y., Toiyama, Y., Yamamoto, A. et al. Modified neutrophil-platelet score as a promising marker for stratified surgical and oncological outcomes of patients with gastric cancer. Surg Today 50, 223–231 (2020). https://doi.org/10.1007/s00595-019-01873-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00595-019-01873-y

Keywords

Search

Navigation