Annals of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회지)

The Korean Association of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회)
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Do changes in inflammatory markers predict hepatocellular carcinoma recurrence and survival after liver transplantation?

  • Lucas Jose Caram (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Francisco Calderon (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Esteban Masino (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Victoria Ardiles (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Ezequiel Mauro (Department of Internal Medicine and Hepatology, Hospital Italiano de Buenos Aires) ;
  • Leila Haddad (Department of Internal Medicine and Hepatology, Hospital Italiano de Buenos Aires) ;
  • Juan Pekolj (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Jimena Vicens (Department of Internal Medicine and Statistics, Hospital Italiano de Buenos Aires) ;
  • Adrian Gadano (Department of Internal Medicine and Hepatology, Hospital Italiano de Buenos Aires) ;
  • Eduardo de Santibanes (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires) ;
  • Martin de Santibanes (Division of Hepato Pancreatic Biliary Surgery and Liver Transplant Unit, Department of General Surgery, Hospital Italiano de Buenos Aires)
  • Received : 2021.06.23
  • Accepted : 2021.09.21
  • Published : 2022.02.28
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Abstract

Backgrounds/Aims: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC). Methods: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated. Results: Serum alpha-fetoprotein levels > 100 ng/mL (p = 0.014) and lymphovascular emboli in the specimen (p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score (p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS. Conclusions: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

Keywords

Acknowledgement

The funding involved in this work has been provided by the National Cancer Institute of Argentina.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. 
  2. International Agency for Research on Cancer (IARC). Fact sheets by population-Globocan-IARC [Internet]. Lyon: IARC 2020 [cited 2016 Dec 18]. Available from: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. 
  3. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-380. 
  4. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693-699. 
  5. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001;33:1394-1403. 
  6. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301-1314. 
  7. Tandon P, Garcia-Tsao G. Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 2009;29:502-510. 
  8. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357:539-545. 
  9. Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD. The codependence of angiogenesis and chronic inflammation. FASEB J 1997;11:457-465. 
  10. Wang D, Bai N, Hu X, OuYang XW, Yao L, Tao Y, et al. Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC. PeerJ 2019;7:e7132. 
  11. 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 2014;9:e101119. 
  12. Zheng J, Cai J, Li H, Zeng K, He L, Fu H, et al. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as prognostic predictors for hepatocellular carcinoma patients with various treatments: a meta-analysis and systematic review. Cell Physiol Biochem 2017;44:967-981. 
  13. Al Lawati Y, Cools-Lartigue J, Ramirez-GarciaLuna JL, Molina-Franjola JC, Pham D, Skothos E, et al. Dynamic alteration of neutrophil-to-lymphocyte ratio over treatment trajectory is associated with survival in esophageal adenocarcinoma. Ann Surg Oncol 2020;27:4413-4419. 
  14. Celik N, Kelly B, Soltys K, Squires JE, Vockley J, Shellmer DA, et al. Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: expanding the donor pool for live donor liver transplantation. Clin Transplant 2019;33:e13721. 
  15. Tsochatzis EA, Germani G, Burroughs AK. Transarterial chemoembolization, transarterial chemotherapy, and intra-arterial chemotherapy for hepatocellular carcinoma treatment. Semin Oncol 2010;37:89-93. 
  16. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol 2013;88:218-230. 
  17. Zhan H, Ma JY, Jian QC. Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in melanoma patients: a meta-analysis. Clin Chim Acta 2018;484:136-140. 
  18. Choi N, Kim JH, Chie EK, Gim J, Kang HC. A meta-analysis of the impact of neutrophil-to-lymphocyte ratio on treatment outcomes after radiotherapy for solid tumors. Medicine (Baltimore) 2019;98:e15369. 
  19. Yu Y, Wang H, Yan A, Wang H, Li X, Liu J, et al. Pretreatment neutrophil to lymphocyte ratio in determining the prognosis of head and neck cancer: a meta-analysis. BMC Cancer 2018;18:383. 
  20. Suh J, Jung JH, Jeong CW, Kwak C, Kim HH, Ku JH. Clinical significance of pre-treated neutrophil-lymphocyte ratio in the management of urothelial carcinoma: a systemic review and meta-analysis. Front Oncol 2019;9:1365. 
  21. Wang Z, Zhan P, Lv Y, Shen K, Wei Y, Liu H, et al. Prognostic role of pretreatment neutrophil-to-lymphocyte ratio in non-small cell lung cancer patients treated with systemic therapy: a meta-analysis. Transl Lung Cancer Res 2019;8:214-226. 
  22. Yuan D, Zhu K, Li K, Yan R, Jia Y, Dang C. The preoperative neutrophil-lymphocyte ratio predicts recurrence and survival among patients undergoing R0 resections of adenocarcinomas of the esophagogastric junction. J Surg Oncol 2014;110:333-340. 
  23. Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, et al. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria. Gastroenterology 2012;143:986-994.e3; quiz e14-e15. 
  24. Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, Fan J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology 2018;154:128-139. 
  25. Mansour A, Watson W, Shayani V, Pickleman J. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery 1997;122:730-735; discussion 735-736. 
  26. Garrison RN, Cryer HM, Howard DA, Polk HC Jr. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann Surg 1984;199:648-655. 
  27. Peng W, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, et al. Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival. J Surg Res 2014;192:402-408. 
  28. Liu J, Lin PC, Zhou BP. Inflammation fuels tumor progress and metastasis. Curr Pharm Des 2015;21:3032-3040.