Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio can Predict Post-operative Complications and Mortality in Patients with Operable Esophageal and Gastric Malignancies

Mohammed Nahid *

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

Saravana Bhoopathi

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

Uma Maheshwaran

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

Karthikeyan M.

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

Benet Duraisamy

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

Krishna Bharath

Department of Surgical Gastroenterology, Tirunelveli Medical College, India.

*Author to whom correspondence should be addressed.


Abstract

Aims: Postoperative complications are a major concern following surgery for upper GI malignancies. Studies have shown that high levels of preoperative inflammatory markers have a poor prognosis. However, the relationship between preoperative platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and postoperative complications after curative resection is unclear. This study aimed to evaluate the efficacy of PLR and NLR in predicting clinical outcomes and postoperative complications in these patients.

Study Design: Single-center prospective observational study

Place and Duration of Study: Sample: Department of Surgical Gastroenterology, Tirunelveli Medical College, between January 2021 and December 2022.

Methodology: This single-center prospective study included 70 patients out of which 55 with gastric cancer underwent D2 gastrectomy and 15 with esophageal cancer underwent transhiatal esophagectomy. We evaluated the relationship between PLR and NLR and postoperative complications (≥grade 1 Clavien-Dindo classification). Using a receiver operating characteristic curve, the area under the curve (AUC) for each parameter was calculated and the power to predict postoperative complications was compared.

Results: 35.71% patients experienced postoperative complications. The AUC values of NLR (0.825) and PLR (0.161) were higher when compared to other preoperative tests in predicting postoperative complications. The optimal cut-off for NLR was 1.71 (sensitivity 96% and specificity 84.4%) and for PLR was 0.56 (sensitivity 20% and specificity 84.4%). Patients in the high NLR group had an increased incidence of complications when compared to the low NLR group. 74% in the low PLR group experienced complications, whereas only 11.6% in the high PLR group experienced grade 1 or higher complications.

Conclusion: Both NLR and PLR may serve as valuable indicators of potential postoperative complications for patients receiving surgery for operable gastric and esophageal cancers.

Keywords: Gastric cancer, esophageal cancer, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, postoperative complications


How to Cite

Nahid , M., Bhoopathi , S., Maheshwaran , U., M. , K., Duraisamy , B., & Bharath , K. (2023). Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio can Predict Post-operative Complications and Mortality in Patients with Operable Esophageal and Gastric Malignancies. Asian Journal of Research and Reports in Gastroenterology, 6(1), 164–176. Retrieved from https://journalajrrga.com/index.php/AJRRGA/article/view/119


References

Song S, Ajani JA. The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 2013;10(2):109–18. DOI: 10.1038/nrgastro.2012.210

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021 Feb 4;71(3):209–49.

DOI: 10.3322/caac.21660

Choksi D, Kolhe KM, Ingle M, Rathi C, Khairnar H, Chauhan SG, et al. Esophageal carcinoma: An epidemiological analysis and study of the time trends over the last 20 years from a single center in India. Journal of Family Medicine and Primary Care. 2020 Mar 1;9(3):1695-9. DOI: 10.4103/jfmpc.jfmpc_1111_19

Brenkman HJ, Haverkamp L, Ruurda JP, et al. Worldwide practice in gastric cancer surgery. World J Gastroenterol. 2016;22: 4041–4048. DOI: 10.3748/wjg.v22.i15.4041

Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. The Lancet. 2016 Nov;388(10060):2654–64. DOI: 10.1016/S0140-6736(16)30354-3

Kataoka K, Takeuchi H, Mizusawa J, Ando M, Tsubosa Y, Koyanagi K, et al. and Japan Esophageal Oncology Group/Japan Clinical Oncology Group. A randomized Phase III trial of thoracoscopic versus open esophagectomy for thoracic esophageal cancer: Japan Clinical Oncology Group Study JCOG1409. Japanese Journal of Clinical Oncology. 2016;46(2):174–177. DOI: 10.1093/jjco/hyt061

Kurita N, Miyata H, Gotoh M, Shimada M, Imura S, Kimura W, et al. Risk Model for Distal Gastrectomy When Treating Gastric Cancer on the Basis of Data From 33,917 Japanese Patients Collected Using a Nationwide Web-based Data Entry System. Annals of Surgery. 2015 Aug; 262(2):295–303. DOI: 10.1097/SLA.0000000000001127

Kanda M, Tanaka C, Kobayashi D, Mizuno A, Tanaka Y, Takami H, et al. Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer. Annals of Surgical Oncology. 2017 Feb 1;24(2):502–9. DOI: 10.1245/s10434-016-5544-1

Proctor MJ, Morrison DS, Talwar D, Balmer SM, Fletcher CD, O’Reilly DSJ, et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study. European Journal of Cancer (Oxford, England: 1990). 2011 Nov 1;47(17):2633–41. DOI: 10.1016/j.ejca.2011.03.028

Proctor MJ, Talwar D, Balmar SM, O’Reilly DSJ, Foulis AK, Horgan PG, et al. 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. British Journal of Cancer. 2010 Sep 7;103(6): 870–6. DOI: 10.1038/sj.bjc.6605855

Orditura M, Galizia G, Diana A, Saccone C, Cobellis L, Ventriglia J, et al. Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: A propensity score-matched analysis. ESMO open. 2016;1(2): e000038. DOI: 10.1136/esmoopen-2016-000038

Miyazaki T, Sakai M, Sohda M, Tanaka N, Yokobori T, Motegi Y, et al. Prognostic significance of inflammatory and nutritional parameters in patients with esophageal cancer. Anticancer Res. 2016;36(12):6557–62. DOI: 10.21873/anticanres.11259.

Zhang H, Zhang L, Cheng ZM, Shi B, Yin Y, Zhu J, et al. Prognostic Significance of Combination of Preoperative Platelet Count and Neutrophil-Lymphocyte Ratio (COP-NLR) in Patients with Non-Small Cell Lung Cancer: Based on a Large Cohort Study. 2015 May 7;10(5):e0126496–6. DOI: 10.1371/journal.pone.0126496

Li S, Xu X, Liang D, Tian G, Song S, He Y. [Prognostic value of blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with gastric cancer]. Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. 2014 Dec 1;36(12):910–5. DOI: 10.3389/fonc.2020.00841

Mori M, Shuto K, Kosugi C, Narushima K, Hayashi H, Matsubara H, et al. An increase in the neutrophil-to-lymphocyte ratio during adjuvant chemotherapy indicates a poor prognosis in patients with stage II or III gastric cancer. BMC Cancer. 2018 Dec;18(1). DOI: 10.1186/s12885-018-5171-2

Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Prognostic Significance of Platelet-Based Inflammatory Indicators in Patients with Gastric Cancer. World Journal of Surgery. 2018 Aug 1;42(8):2542–50. DOI: 10.1007/s00268-018-4527-8

Aoyama T, Ju M, Komori K, Takahashi H, Tamagawa A, Onodera A, et al. The Platel*et-to-Lymphocyte Ratio Is an Independent Prognostic Factor for Patients With Esophageal Cancer Who Receive Curative Treatment. 2022 Jan 1;36(4): 1916–22. DOI: 10.21873/invivo.12912

Sakin A. Prognostic significance of neutrophil to lymphocyte ratio in esophageal squamous cell carcinoma. Northern Clinics of Istanbul. 2020;8(5):435. DOI: 10.14744/nci.2020.63004

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. British Journal of Cancer. 2009 Mar 24; 100(8):1236–9. DOI: 10.1038/sj.bjc.6604997

Zhou X, Du Y, Huang Z, Xu J, Qiu T, Wang J, et al. Prognostic Value of PLR in Various Cancers: A Meta-Analysis. Scheurer M, editor. PLoS ONE. 2014 Jun 26;9(6): e101119. DOI: 10.1371/journal.pone.0101119

Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo Classification of Surgical Complications. Annals of Surgery. 2009 Aug;250(2):187–96. DOI: 10.1097/SLA.0b013e3181b13ca2

Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging: The Eighth Edition AJCC Cancer Staging Manual. CA Cancer J Clin. 2017;67(2):93–9. DOI: 10.3322/caac.21388

Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017 Mar;161(3):584–91. DOI: 10.1016/j.surg.2016.11.014

Kieninger AN, Lipsett PA. Hospital-Acquired Pneumonia: Pathophysiology, Diagnosis, and Treatment. Surgical Clinics of North America. 2009 Apr 1;89(2):439–61. DOI: 10.1016/j.suc.2008.11.001

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American journal of respiratory and critical care medicine. 2005;171(4):388–416. DOI: 10.1164/rccm.200405-644ST

Strobel O, Brangs S, Hinz U, Pausch T, Hüttner FJ, Diener MK, et al. Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery. The British Journal of Surgery. 2017 Jan 1;104(1):108–17. DOI: 10.1002/bjs.10316

Takahashi R, Ohashi M, Hiki N, Makuuchi R, Ida S, Kumagai K, et al. Risk factors and prognosis of gastric stasis, a crucial problem after laparoscopic pylorus-preserving gastrectomy for early middle-third gastric cancer. Gastric Cancer. 2020 Jan 8;23(4):707–15. DOI: 10.1007/s10120-019-01037-4

Sgambato A, Cittadini A. Inflammation and cancer: a multifaceted link. Eur Rev Med Pharmacol Sci. 2010;14(4):263–8.

Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–14. DOI: 10.1053/j.gastro.2010.01.058

Brown DJ, Milroy R, Preston T, McMillan DC. The relationship between an inflammation-based prognostic score (Glasgow Prognostic Score) and changes in serum biochemical variables in patients with advanced lung and gastrointestinal cancer. J Clin Pathology. 2007;60(6):705–8. DOI: 10.1136/jcp.2005.033217

Ishizuka M, Nagata H, Takagi K, Horie T, Kubota K. Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surgery. 2007;246(6):1047–51.DOI: 10.1097/SLA.0b013e3181454171

Kobayashi T, Teruya M, Kishiki T, Endo D, Takenaka Y, Tanaka H, Miki K, Kobayashi K, Morita K. Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma. Surgery. 2008;144(5): 729–35. DOI: 10.1016/j.surg.2008.08.015

Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer. Critical reviews in Oncology/Hematology. 2013;88(1): 218– 30. DOI: 10.1016/j.critrevonc.2013.03.010

Maruyama Y, Inoue K, Mori K, Gorai K, Shimamoto R, Onitsuka T, Iguchi H, Okazaki M, Nakagawa M. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of wound healing failure in head and neck reconstruction. Acta oto-laryngologica. 2017;137(1):106–10. DOI: 10.3892/mco.2018.1698

Vulliamy P, McCluney S, Mukherjee S, Ashby L, Amalesh T. Postoperative elevation of the neutrophil: lymphocyte ratio predicts complications following esophageal resection. World journal of surgery. 2016;40(6):1397– 403. DOI: 10.1007/s00268-016-3427-z

Dionigi R, Dominioni L, Benevento A, Giudice G, Cuffari S, Bordone N, et al. Effects of surgical trauma of laparoscopic vs. open cholecystectomy. Hepatogastroenterology. 41(5):471–6

Braga M, Vignali A, Zuliani W, Radaelli G, Gianotti L, Martani C, et al. Metabolic and functional results after laparoscopic colorectal surgery: A randomized, controlled trial. Dis Colon Rectum [Internet]. 2002 [cited 2023 Feb 17];45(8): 1070–7. DOI: 10.1007/s10350-004-6362-2

Inaoka K, Kanda M, Uda H, Tanaka Y, Tanaka C, Kobayashi D, et al. Clinical utility of the platelet-lymphocyte ratio as a predictor of postoperative complications after radical gastrectomy for clinical T2-4 gastric cancer. World J Gastroenterol [Internet]. 2017 [cited 2023 Feb 17];23(14): 2519.

DOI: 10.3748/wjg.v23.i14.2519

Kanda M, Mizuno A, Tanaka C, Kobayashi D, Fujiwara M, Iwata N, Hayashi M, Yamada S, Nakayama G, Fujii T, et al. Nutritional predictors for postoperative short-term and long-term outcomes of patients with gastric cancer. Medicine (Baltimore) 2016;95:e3781. DOI: 10.1097/MD.0000000000003781

Pang W, Lou N, Jin C, Hu C, Arvine C, Zhu G, Shen X. Combination of preoperative platelet/lymphocyte and neutrophil/lymphocyte rates and tumor-related factors to predict lymph node metastasis in patients with gastric cancer. Eur J Gastroenterol Hepatol. 2016;28:493–502. DOI: 10.1097/MEG.0000000000000563

Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, Šeruga B, Ocana A, Tannock IF, Amir E. Prognostic role of platelet to lymphocyte ratio in solid tumors: A systematic review and meta-analysis. Cancer Epidemiol Prevent Biomarkers. 2014;23(7):1204. DOI: 10.1158/1055-9965.EPI-14-0146

Okamura Y, Ashida R, Ito T, Sugiura T, Mori K, Uesaka K. Preoperative neutrophil to lymphocyte ratio and prognostic nutritional index predict overall survival after hepatectomy for hepatocellular carcinoma. World J Surg. 2015;39:1501–1509. DOI: 10.1007/s00268-015-2982-z

Kim EY, Lee JW, Yoo HM, Park CH, Song KY. The Platelet-to-Lymphocyte Ratio Versus Neutrophil-to-Lymphocyte Ratio: Which is Better as a Prognostic Factor in Gastric Cancer? Ann Surg Oncol. 2015;22:4363–4370. DOI: 10.1245/s10434-015-4518-z

Zhou X, Du Y, Huang Z, Xu J, Qiu T, Wang J, et al. Prognostic value of PLR in various cancers: A meta-analysis. PLoS One [Internet]. 2014;9(6):e101119.

DOI: 10.1371/journal.pone.0101119

Mungan İ, Dicle ÇB, Bektaş Ş, Sarı S, Yamanyar S, Çavuş M, et al. Does the preoperative platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio predict morbidity after gastrectomy for gastric cancer? Military Medical Research. 2020 Feb 29;7(1). DOI: 10.1186/s40779-020-00234-y

Zhang Y, Lu JJ, Du YP, Feng CX, Wang LQ, Chen MB. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in gastric cancer. Medicine. 2018;97(12):e0144. DOI: 10.1097/MD.0000000000010144

Xie X, Luo KJ ., Hu Y, Wang JY ., Chen J. Prognostic value of preoperative platelet-lymphocyte and neutrophil-lymphocyte ratio in patients undergoing surgery for esophageal squamous cell cancer. Diseases of the Esophagus. 2014 Nov 19;29(1):79–85. DOI: 10.1111/dote.12296

Zubiaga L, Ruis-Tovar J. Correlation of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with metabolic parameters in patients undergoing sleeve gastrectomy Sugery Obesity Related Dis. 2020;16:999-1004

Mori M, et al.Preoperative Neutrophil-to-lymphocyte Ratio May Predict Postoperative Pneumonia in Stage I–III Gastric Cancer Patients After Curative Gastrectomy: A Retrospective Study World J Surg. 2021;45:3359-69

Kwak JS, et al. The role of postoperative neutrophil-to-lymphocyte ratio as a predictor of postoperative major complications following total gastrectomy for gastric cancer Ann Surg Treat Res. 2022;103:153-9

Onuma S, et al. Clinical Effects of the Neutrophil-to-Lymphocyte Ratio/Serum Albumin Ratio in Patients with Gastric Cancer after Gastrectomy J. Pers. Med. 2023;13:432-43.

Szor DJ, et al. Neutrophil-lymphocyte ratio change after curative gastrectomy for gastric cancer: A subgroup analysis Einstein (São Paulo). 2020;18:1- 7.

Meguid RA, Bronsert MR, Juarez-Colunga E, Hammermeister KE, Henderson WG. Surgical Risk Preoperative Assessment System (SURPAS): III. Accurate Preoperative Prediction of 8 Adverse Outcomes Using 8 Predictor Variables. Ann Surg. 2016;264: 23–31. DOI: 10.1097/SLA.0000000000001678.

Chen T, Wang H, Wang H, Song Y, Li X, Wang J. POSSUM and P-POSSUM as predictors of postoperative morbidity and mortality in patients undergoing hepato-biliary-pancreatic surgery: A meta-analysis. Ann Surg Oncol. 2013;20:2501–2510. DOI: 10.1245/s10434-013-2893-x.