Abstract
Background
This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC).
Methods
Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed.
Results
A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15–85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR ≥5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR ≥ 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR ≥ 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR ≥ 5 was 8 months compared with 18 months for those with a NLR < 5.
Conclusion
Preoperative NLR ≥ 5 was an adverse predictor of disease-free and overall survival.
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References
El-Serag HB, Mason AC (1999) Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750
Llovet JM, Schwartz M, Mazzaferro V (2005) Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25:181–200
Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236
Yeh CN, Chen MF, Lee WC, Jeng LB (2002) Prognostic factors of hepatic resection for hepatocellular carcinoma with cirrhosis: univariate and multivariate analysis. J Surg Oncol 81:195–202
Regimbeau JM, Abdalla EK, Vauthey JN, Lauwers GY, Durand F, Nagorney DM, Ikai I, Yamaoka Y, Belghiti J (2004) Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study. J Surg Oncol 85:36–41
Grazi GL, Cescon M, Ravaioli M, Ercolani G, Gardini A, Del Gaudio M, Vetrone G, Cavallari A (2003) Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre. Aliment Pharmacol Ther 17(Suppl 2):119–129
Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440
Nagasue N, Ono T, Yamanoi A, Kohno H, El-Assal ON, Taniura H, Uchida M (2001) Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis. Br J Surg 88:515–522
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867
Gunter MJ, Stolzenberg-Solomon R, Cross AJ, Leitzmann MF, Weinstein S, Wood RJ, Virtamo J, Taylor PR, Albanes D, Sinha R (2006) A prospective study of serum C-reactive protein and colorectal cancer risk in men. Cancer Res 66:2483–2487
Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545
Jaiswal M, LaRusso NF, Burgart LJ, Gores GJ (2000) Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res 60:184–190
McMillan DC, Canna K, McArdle CS (2003) Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 90:215–219
Zahorec R (2001) Ratio of neutrophil to lymphocyte counts–rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102:5–14
Hashimoto K, Ikeda Y, Korenaga D, Tanoue K, Hamatake M, Kawasaki K, Yamaoka T, Iwatani Y, Akazawa K, Takenaka K (2005) The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer 103:1856–1864
McMillan DC, Wotherspoon HA, Fearon KC, Sturgeon C, Cooke TG, McArdle CS (1995) A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery. Am J Surg 170:319–322
Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL (2006) Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol 97:993–996
Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ (2005) Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol 91:181–184
Halazun KJ, Aldoori A, Malik HZ, Al-Mukhtar A, Prasad KR, Toogood GJ, Lodge JP (2008) Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol 34:55–60
Strasberg SM (2005) Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary Pancreat Surg 12:351–355
Wong VK, Malik HZ, Hamady ZZ, Al-Mukhtar A, Gomez D, Prasad KR, Toogood GJ, Lodge JP (2007) C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases. Br J Cancer 96:222–225
Young AL, Malik HZ, Abu-Hilal M, Guthrie JA, Wyatt J, Prasad KR, Toogood GJ, Lodge JP (2007) Large hepatocellular carcinoma: time to stop preoperative biopsy. J Am Coll Surg 205:453–462
Vauthey JN, Klimstra D, Franceschi D, Tao Y, Fortner J, Blumgart L, Brennan M (1995) Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma. Am J Surg 169:28–35
Lang H, Sotiropoulos GC, Domland M, Fruhauf NR, Paul A, Husing J, Malago M, Broelsch CE (2005) Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Br J Surg 92:198–202
Lee NH, Chau GY, Lui WY, King KL, Tsay SH, Wu CW (1998) Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter. Br J Surg 85:1654–1657
Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230:309–321
Ercolani G, Grazi GL, Ravaioli M, Del Gaudio M, Gardini A, Cescon M, Varotti G, Cetta F, Cavallari A (2003) Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 237:536–543
Lise M, Bacchetti S, Da Pian P, Nitti D, Pilati PL, Pigato P (1998) Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients. Cancer 82:1028–1036
Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S (1998) Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 28:1241–1246
Poon RT, Fan ST, Lo CM, Liu CL, Wong J (2002) Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 235:373–382
Ziparo V, Balducci G, Lucandri G, Mercantini P, Di Giacomo G, Fernandes E (2002) Indications and results of resection for hepatocellular carcinoma. Eur J Surg Oncol 28:723–728
Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, Wong J (2001). Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg 234:63–70
Svennevig JL, Lunde OC, Holter J, Bjorgsvik D (1984) Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 49:375–377
Okano K, Maeba T, Moroguchi A, Ishimura K, Karasawa Y, Izuishi K, Goda F, Usuki H, Wakabayashi H, Maeta H (2003) Lymphocytic infiltration surrounding liver metastases from colorectal cancer. J Surg Oncol 82:28–33
Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH (2003) Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 6:283–287
Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, Volant A, Pera M (2004) p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer 90:206–215
Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T (1997) Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol 15:826–832
Garden OJ, Rees M, Poston GJ, Mirza D, Saunders M, Ledermann J, Primrose JN, Parks RW (2006) Guidelines for resection of colorectal cancer liver metastases. Gut 55(Suppl 3):iii1–8
Xavier P, Belo L, Beires J, Rebelo I, Martinez-de-Oliveira J, Lunet N, Barros H (2006) Serum levels of VEGF and TNF-alpha and their association with C-reactive protein in patients with endometriosis. Arch Gynecol Obstet 273:227–231
Canna K, McArdle PA, McMillan DC, McNicol AM, Smith GW, McKee RF, McArdle CS (2005) The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer 92:651–654
Fenwick SW, Toogood GJ, Lodge JP, Hull MA (2003) The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases. Gastroenterology 125:716–729
Chalmers CR, Wilson DJ, Ward J, Robinson PJ, Toogood GJ, Hull MA (2006) Antiangiogenic activity of the selective cyclooxygenase-2 inhibitor rofecoxib in human colorectal cancer liver metastases. Gut 55:1058–1059
Lesterhuis WJ, de Vries IJ, Schuurhuis DH, Boullart AC, Jacobs JF, de Boer AJ, Scharenborg NM, Brouwer HM, van de Rakt MW, Figdor CG, Ruers TJ, Adema GJ, Punt CJ (2006) Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests. Ann Oncol 17:974–980
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Gomez, D., Farid, S., Malik, H.Z. et al. Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor after Curative Resection for Hepatocellular Carcinoma. World J Surg 32, 1757–1762 (2008). https://doi.org/10.1007/s00268-008-9552-6
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DOI: https://doi.org/10.1007/s00268-008-9552-6