Factors independently associated with prognosis in patients operated for pancreatic cancer: Assessing the role of various parameters including red cell distribution width, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio

Year 2022, Volume: 5 Issue: 5, 1319 - 1327, 25.09.2022

Ahmet Karayiğit , Dursun Burak Özdemir , Hayrettin Dizen , Bülent Ünal

https://doi.org/10.32322/jhsm.1137856

Abstract

Objective: We aimed to assess whether, among other parameters, preoperative red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) values were associated with prognosis in patients operated for pancreatic cancer (PC).
Material and Method: This retrospective cohort was conducted from February 1, 2016 to February 1, 2021 at the general surgery department of a university hospital in Turkey. A total of 75 patients histologically diagnosed with PC who had undergone surgery were included in the study.
Results: The PLR values of patients with poorly differentiated and undifferentiated tumors were found to be higher than those with moderately and highly differentiated tumors. Also, there was a significant relationship between PLR values and the length of hospital stay. PLR values increased as the length of hospital stay increased. There was a statistically significant positive correlation between CA 19-9 levels and NLR and PLR. High total bilirubin level was related with increased risk of death, while adjuvant chemotherapy recipients had 4.049-fold lower risk of death than those without adjuvant chemotherapy.
Conclusion: Our results indicate that preoperative NLR, PLR and RDW cannot be used as prognostic indicators of mortality in patients with operated PC, but high PLR appears to be associated with lower level of tumor differentiation and prolonged hospital stay. We also found that high total bilirubin was a poor prognostic factor, while adjuvant chemotherapy was a good prognostic factor. Further multicenter, prospective studies with larger sample sizes will help to verify these results.

Keywords

Pancreatic cancer, NLR, PLR, RDW, CA 19-9, bilirubin

References

• Oh D, Pyo J-S, Son BK. Prognostic roles of inflammatory markers in pancreatic cancer: comparison between the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio. Gastroenterol Res Pract 2018; 2018: 9745601.
• Zhou Y, Cheng S, Fathy AH, Qian H, Zhao Y. Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies. Onco Targets Ther 2018; 11: 1899.
• Zhiyao F, Guopei L, Yitao G, Liu C, Xianjun Y. ASO author reflections: C-reactive protein/lymphocyte ratio as a promising marker for predicting survival in pancreatic cancer. Ann Surg Oncol 2020; 27: 4026-7.
• Yang J-J, Hu Z-G, Shi W-X, Deng T, He S-Q, Yuan S-G. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis. World J Gastroenterol 2015; 21: 2807-15.
• Riauka R, Ignatavicius P, Barauskas G. Preoperative platelet to lymphocyte ratio as a prognostic factor for resectable pancreatic cancer: a systematic review and meta-analysis. Dig Surg 2020; 37: 436-44.
• Feng L, Gu S, Wang P, et al. Pretreatment values of bilirubin and albumin are not prognostic predictors in patients with advanced pancreatic cancer. Cancer Med 2018; 7: 5943-51.
• Temme EH, Zhang J, Schouten EG, Kesteloot H. Serum bilirubin and 10-year mortality risk in a Belgian population. Cancer Causes Control 2001; 12: 887-94.
• Giakoustidis A, Neofytou K, Neves MC, et al. Identifying the role of neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio as prognostic markers in patients undergoing resection of pancreatic ductal adenocarcinoma. Ann Hepatobiliary Pancreat Surg 2018; 22: 197-207.
• Kwon H-C, Kim SH, Oh SY, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers 2012; 17: 216-22.
• Dang C, Wang M, Qin T, Qin R. Clinical importance of preoperative red-cell volume distribution width as a prognostic marker in patients undergoing radical surgery for pancreatic cancer. Surg Today 2021: 1-10.
• Mowbray NG, Griffith D, Hammoda M, Shingler G, Kambal A, Al-Sarireh B. A meta-analysis of the utility of the neutrophil-to-lymphocyte ratio in predicting survival after pancreatic cancer resection. HPB (Oxford) 2018; 20: 379-84.
• Xu Z-S, Zhang F-P, Zhang Y, et al. Prognostic role of the pre-treatment platelet-lymphocyte ratio in pancreatic cancer: a meta-analysis. Oncotarget 2017; 8: 99003.
• Akturk O, Çakir M. The discriminative properties of erythrocyte anisocytosis in patients with resectable malignant pancreatic masses compared with an age and gender matched control group. Il Giornale di chirurgia 2020; 41: 34-9.
• Smirne C, Grossi G, Pinato DJ, et al. Evaluation of the red cell distribution width as a biomarker of early mortality in hepatocellular carcinoma. Dig Liver Dis 2015; 47: 488-94.
• Koma Y, Onishi A, Matsuoka H, et al. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer. PLoS One 2013; 8: e80240.
• Shirai Y, Shiba H, Sakamoto T, et al. Preoperative platelet to lymphocyte ratio predicts outcome of patients with pancreatic ductal adenocarcinoma after pancreatic resection. Surgery 2015; 158: 360-5.
• Spolverato G, Maqsood H, Kim Y, et al. Neutrophil‐lymphocyte and platelet‐lymphocyte ratio in patients after resection for hepato‐pancreatico‐biliary malignancies. J Surg Oncol 2015; 111: 868-74.
• Smith RA, Bosonnet L, Raraty M, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg 2009; 197: 466-72.
• Zhou X, Du Y, Huang Z, et al. Prognostic value of PLR in various cancers: a meta-analysis. PLoS One 2014; 9: e101119.
• Kishi T, Nakamura A, Itasaka S, et al. Pretreatment C-reactive protein level predicts outcome and patterns of failure after chemoradiotherapy for locally advanced pancreatic cancer. Pancreatology 2015; 15: 694-700.
• Varol U, Kaya E, Oflazoglu U, et al. Prognostic role of De Ritis and basal neutrophil to lymphocyte ratio in patients with advanced stage pancreatic cancer [İzmir Oncology Group (IZOG) Study]. JBUON 2020; 25: 1063-9
• Cheng H, Luo G, Lu Y, et al. The combination of systemic inflammation-based marker NLR and circulating regulatory T cells predicts the prognosis of resectable pancreatic cancer patients. Pancreatology 2016; 16: 1080-4.
• Ong S, Garcea G, Thomasset S, et al. Surrogate markers of resectability in patients undergoing exploration of potentially resectable pancreatic adenocarcinoma. J Gastrointest Surg 2008; 12: 1068-73.
• Asaoka T, Miyamoto A, Maeda S, et al. Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer. Pancreatology 2016; 16: 434-40.
• Li Q, Feng Z, Miao R, Liu X, Liu C, Liu Z. Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution. World J Surg Oncol 2022; 20: 1-16.
• Hasegawa S, Eguchi H, Tomokuni A, 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: 1560-6.
• Wang D-S, Luo H-Y, Qiu M-Z, et al. Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med Oncol 2012; 29: 3092-100.
• Piciucchi M, Stigliano S, Archibugi L, et al. The neutrophil/lymphocyte ratio at diagnosis is significantly associated with survival in metastatic pancreatic cancer patients. Int J Mol Sci 2017; 18: 730.
• Guo J, Wu M, Guo L, Zuo Q. Pretreatment blood neutrophil/lymphocyte ratio is associated with metastasis and predicts survival in patients with pancreatic cancer. Bull Cancer 2018; 105: 146-54.
• Yilmaz A, Malya F, Ozturk G, et al. Effect of pre-operative red blood cell distribution on cancer stage and morbidity rate in patients with pancreatic cancer. Int J Clin Exp Med 2014; 7: 3072.
• Yagyu T, Saito H, Sakamoto T, et al. Preoperative albumin-bilirubin grade as a useful prognostic indicator in patients with pancreatic cancer. Anticancer Res 2019; 39: 1441-6.
• Scarà S, Bottoni P, Scatena R. CA 19-9: biochemical and clinical aspects. Advances in Cancer Biomarkers 2015: 247-60.
• Nishida K, Kaneko T, Yoneda M, et al. Doubling time of serum CA 19‐9 in the clinical course of patients with pancreatic cancer and its significant association with prognosis. J Surg Oncol 1999; 71: 140-6.
• Boeck S, Ankerst DP, Heinemann V. The role of adjuvant chemotherapy for patients with resected pancreatic cancer: systematic review of randomized controlled trials and meta-analysis. Oncology 2007; 72: 314-21.
• Bakkevold KE, Arnesjø B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater—results of a controlled, prospective, randomised multicentre study. Eur J Cancer 1993; 29: 698-703.
• Nakata B, Amano R, Kimura K, Hirakawa K. Comparison of prognosis between patients of pancreatic head cancer with and without obstructive jaundice at diagnosis. Int J Surg 2013; 11: 344-9.
• Aziz MH, Sideras K, Aziz NA, et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann Surg 2019; 270: 139-46.