Ann Hepatobiliary Pancreat Surg.  2018 Aug;22(3):197-207. 10.14701/ahbps.2018.22.3.197.

Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio as prognostic markers in patients undergoing resection of pancreatic ductal adenocarcinoma

• Giakoustidis A
• Neofytou K
• Costa Neves M
• Giakoustidis D
• Louri E
• Cunningham D
• Mudan S

• KMID: 2420608
• DOI: http://doi.org/10.14701/ahbps.2018.22.3.197

Abstract

BACKGROUNDS/AIMS
It is important to point out that the identification of inflammation is an essential component of the pathogenesis and the progression of cancer. In this study, we analysed the neutrophil-to-lymphocyte ratio (NLR) and the platelets-to-lymphocyte ratio (PLR), with an overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC), who were treated with a resection following or not following a procedure of neoadjuvant chemotherapy/chemoradiation. We intended to identify the significance of the role of NLR and PLR, as prognostic markers in patients undergoing surgery for PDAC.
METHODS
There were 127 patients enrolled in the study. The NLR and PLR were calculated on the basis of the pre-treatment blood cell count. An NLR>4 and a PLR >120 were considered to be elevated as measured. OS was analysed in relation to the NLR and PLR values, by using both the Kaplan-Meier and multivariate Cox-regression methods.
RESULTS
Both high the NLR and high PLR were associated with a decreased OS in the univariate analysis. In the multivariate analysis, the high NLR, but not the high PLR, was an independent predictor of a decreased OS. When we divided patients into three groups (group 1: normal both NLR and PLR, group 2: high NLR or high PLR, group 3: high both NLR and PLR), the three-years OS rates for these groups were 48%, 32%, 7% (p=0.001) respectively.
CONCLUSIONS
It is noted that the pre-treatment NLR is an independent adverse prognostic factor, and considered to be superior to the PLR, in patients who undergo a resection for PDAC following or not neoadjuvant chemotherapy/chemoradiation.

Keyword

Pancreatic ductal adenocarcinoma; Inflammation; NLR; PLR; Prognostic factor

MeSH Terms

Adenocarcinoma*
Blood Cell Count
Humans
Inflammation
Multivariate Analysis
Pancreatic Ducts*

Figure

• 

  Fig. 1 Consort diagram of the study.

• 

  Fig. 2 Pre treatment NLR, PLR and their combination and overall survival.

Reference

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012; 62:10–29.

2. Cohen SJ, Pinover WH, Watson JC, Meropol NJ. Pancreatic cancer. Curr Treat Options Oncol. 2000; 1:375–386.

3. Geng Y, Qi Q, Sun M, Chen H, Wang P, Chen Z. Prognostic nutritional index predicts survival and correlates with systemic inflammatory response in advanced pancreatic cancer. Eur J Surg Oncol. 2015; 41:1508–1514.

4. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013; 33:Suppl 1. S79–S84.

5. Servais C, Erez N. From sentinel cells to inflammatory culprits: cancer-associated fibroblasts in tumour-related inflammation. J Pathol. 2013; 229:198–207.

6. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420:860–867.

7. Stevens L, Pathak S, Nunes QM, Pandanaboyana S, Macutkiewicz C, Smart N, et al. Prognostic significance of preoperative C-reactive protein and the neutrophil-lymphocyte ratio in resectable pancreatic cancer: a systematic review. HPB (Oxford). 2015; 17:285–291.

8. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357:539–545.

9. Kwon HC, Kim SH, Oh SY, Lee S, Lee JH, Choi HJ, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012; 17:216–222.

10. Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Br J Cancer. 2012; 107:695–699.

11. Mallappa S, Sinha A, Gupta S, Chadwick SJ. Preoperative neutrophil to lymphocyte ratio >5 is a prognostic factor for recurrent colorectal cancer. Colorectal Dis. 2013; 15:323–328.

12. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454:436–444.

13. Jamieson NB, Denley SM, Logue J, MacKenzie DJ, Foulis AK, Dickson EJ, et al. A prospective comparison of the prognostic value of tumor- and patient-related factors in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2011; 18:2318–2328.

14. Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013; 58:58–64.

15. Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Okamura Y. Elevated preoperative neutrophil-to-lymphocyte ratio as a predictor of survival after gastroenterostomy in patients with advanced pancreatic adenocarcinoma. Ann Surg Oncol. 2013; 20:4330–4337.

16. Halazun KJ, Aldoori A, Malik HZ, Al-Mukhtar A, Prasad KR, Toogood GJ, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol. 2008; 34:55–60.

17. Malietzis G, Giacometti M, Askari A, Nachiappan S, Kennedy RH, Faiz OD, et al. A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery. Ann Surg. 2014; 260:287–292.

18. Szkandera J, Pichler M, Absenger G, Stotz M, Arminger F, Weissmueller M, et al. The elevated preoperative platelet to lymphocyte ratio predicts decreased time to recurrence in colon cancer patients. Am J Surg. 2014; 208:210–214.

19. Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer. 2014; 110:435–440.

20. Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013; 39:782–795.

21. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014; 232:199–209.

22. Kishi Y, Kopetz S, Chun YS, Palavecino M, Abdalla EK, Vauthey JN. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009; 16:614–622.

23. Gomez D, Morris-Stiff G, Toogood GJ, Lodge JP, Prasad KR. Impact of systemic inflammation on outcome following resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 2008; 97:513–518.

24. Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008; 32:1757–1762.

25. Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013; 109:416–421.

26. Giakoustidis A, Neofytou K, Khan AZ, Mudan S. Neutrophil to lymphocyte ratio predicts pattern of recurrence in patients undergoing liver resection for colorectal liver metastasis and thus the overall survival. J Surg Oncol. 2015; 111:445–450.

27. Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011; 13:499–503.

28. Krenn-Pilko S, Langsenlehner U, Thurner EM, Stojakovic T, Pichler M, Gerger A, et al. The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients. Br J Cancer. 2014; 110:2524–2530.

29. Neofytou K, Smyth EC, Giakoustidis A, Khan AZ, Cunningham D, Mudan S. Elevated platelet to lymphocyte ratio predicts poor prognosis after hepatectomy for liver-only colorectal metastases, and it is superior to neutrophil to lymphocyte ratio as an adverse prognostic factor. Med Oncol. 2014; 31:239.

30. Jenne CN, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol. 2013; 35:254–261.

31. Egan K, Crowley D, Smyth P, O'Toole S, Spillane C, Martin C, et al. Platelet adhesion and degranulation induce pro-survival and pro-angiogenic signalling in ovarian cancer cells. PLoS One. 2011; 6:e26125.

32. Arima K, Okabe H, Hashimoto D, Chikamoto A, Tsuji A, Yamamura K, et al. The diagnostic role of the neutrophil-to-lymphocyte ratio in predicting pancreatic ductal adenocarcinoma in patients with pancreatic diseases. Int J Clin Oncol. 2016; 21:940–945.

33. Hasegawa S, Eguchi H, Tomokuni A, Tomimaru Y, Asaoka T, Wada H, et al. Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer. Oncol Lett. 2016; 11:1560–1566.

34. Luo G, Guo M, Liu Z, Xiao Z, Jin K, Long J, et al. Blood neutrophil-lymphocyte ratio predicts survival in patients with advanced pancreatic cancer treated with chemotherapy. Ann Surg Oncol. 2015; 22:670–676.

35. Fischer LK, Katz MH, Lee SM, Liu L, Wang H, Varadhachary GR, et al. The number and ratio of positive lymph nodes affect pancreatic cancer patient survival after neoadjuvant therapy and pancreaticoduodenectomy. Histopathology. 2016; 68:210–220.

36. Huebner M, Kendrick M, Reid-Lombardo KM, Que F, Therneau T, Qin R, et al. Number of lymph nodes evaluated: prognostic value in pancreatic adenocarcinoma. J Gastrointest Surg. 2012; 16:920–926.

37. Schwarz RE, Smith DD. Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database. Ann Surg Oncol. 2006; 13:1189–1200.

38. Slidell MB, Chang DC, Cameron JL, Wolfgang C, Herman JM, Schulick RD, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008; 15:165–174.

39. Wang DS, Luo HY, Qiu MZ, Wang ZQ, Zhang DS, Wang FH, et al. Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol. 2012; 29:3092–3100.

40. Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP. Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg. 2011; 35:868–872.

41. Spolverato G, Maqsood H, Kim Y, Margonis G, Luo T, Ejaz A, et al. Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary malignancies. J Surg Oncol. 2015; 111:868–874.