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      Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Primary Liver Cancer: A Meta-Analysis

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          Abstract

          The neutrophil-to-lymphocyte ratio (NLR) is a useful biomarker that reflects systemic inflammation responses. However, the prognostic value of the NLR in patients with primary liver cancer (PLC) remains controversial. We performed a meta-analysis of 26 studies (comprising 4,461 patients) to evaluate the association between the pre-treatment NLR and clinical outcomes of overall survival (OS) and disease-free survival (DFS) in patients with PLC. The correlation between NLR and tumor characteristics or other inflammation-related parameters was also assessed. Data were synthesized using the random-effects model of DerSimonian and Laird, and the hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to estimate effect size. Our analysis indicated that a high NLR predicted poor OS (HR, 2.102; 95% CI: 1.741–2.538) and DFS (HR, 2.474; 95% CI: 1.855–3.300) for PLC. A high NLR was associated with the presence of tumor vascular invasion (OR: 1.889, 95% CI: 1.487–2.400; p<0.001) and an elevated alpha-fetoprotein level (OR: 1.536; 95% CI: 1.152–2.048; p = 0.003). Thus, we conclude that a high NLR indicates a poor prognosis for patients with PLC and may also be predictive for PLC invasion and metastasis. Subgroup analysis suggested that the predictive role of NLR in cholangiocarcinoma is limited, and a further large study to confirm these findings is warranted.

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          Most cited references29

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          Microenvironmental regulation of metastasis.

          Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.
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            Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma.

            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). 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. 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 >or=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 >or= 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR >or= 5 was 8 months compared with 18 months for those with a NLR or= 5 was an adverse predictor of disease-free and overall survival.
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              Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma.

              The Milan criteria have been adopted by United Network for Organ Sharing (UNOS) to preoperatively assess outcome in patients with hepatocellular carcinoma (HCC) who receive orthotopic liver transplantation (OLT). These criteria rely solely on radiographic appearances of the tumor, providing no measure of tumor biology. Recurrence rates, therefore, remain around 20% for patients within the criteria. The neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status previously established as a prognostic indicator in colorectal liver metastases. We aimed to determine whether NLR predicts outcome in patients undergoing OLT for HCC. Analysis of patients undergoing OLT for HCC between 2001 and 2007 at our institution. A NLR > or =5 was considered to be elevated. : A total of 150 patients were identified, with 13 patients having an elevated NLR. Of these, 62% developed recurrence compared with 14% with normal NLR (P or =5 were significant predictors of poor disease-free survival. However, only a raised NLR remained significant on multivariate analysis (P = 0.005, HR: 19.98). Elevated NLR significantly increases the risk for tumor recurrence and recipient death. Preoperative NLR measurement may provide a simple method of identifying patients with poorer prognosis and act as an adjunct to Milan in determining, which patients benefit most from OLT.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                2 May 2014
                : 9
                : 5
                : e96072
                Affiliations
                [1 ]Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
                [2 ]Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China
                [3 ]Department of Medical Statistics, Zhongshan Hospital, Fudan University, Shanghai, P.R. China
                University of Pisa, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZGR. Performed the experiments: TCX LZ XYX. Analyzed the data: TCX LXL BHZ. Contributed reagents/materials/analysis tools: TCX NLG SLY. Wrote the paper: TCX.

                Article
                PONE-D-13-53139
                10.1371/journal.pone.0096072
                4008563
                24788770
                5057b5ed-c8a6-434e-b0f5-e6e0aa2c7dda
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 December 2013
                : 2 April 2014
                Page count
                Pages: 11
                Funding
                This work was supported by The National Clinical Key Special Subject of China, The National Natural Science Foundation of China (81172275 and 21272565) and The National Basic Research Program of China (973 Program, 2009CB521700). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Hepatocellular Carcinoma
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Cancer Detection and Diagnosis
                Cancer Prevention
                Cancer Treatment

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                Uncategorized

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