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      Prognostic value of pre-operative inflammatory response biomarkers in gastric cancer patients and the construction of a predictive model

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          Abstract

          Background

          Inflammation plays an integral role in carcinogenesis and tumor progression. Inflammatory response biomarkers have shown to be promising prognostic factors for improving the predictive accuracy in various cancers. The aim of this study is to investigate the prognostic significance of pre-operative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in gastric cancer (GC).

          Methods

          389 patients who had undergone gastrectomy were enrolled from 2007 to 2009 in this study. NLR, dNLR, PLR and LMR were calculated from peripheral blood cell count taken at pre-operation. Receiver operating curve (ROC) was used to determine the optimal cut-off levels for these biomarkers. A predictive model or nomogram was established to predict prognosis for cancer-specific survival (CSS) and disease-free survival (DFS), and the predictive accuracy of the nomogram was determined by concordance index (c-index).

          Results

          The median follow-up period was 24 months ranging from 3 months to 60 months. The optimal cut-off levels were 2.36 for NLR, 1.85 for dNLR, 132 for PLR and 4.95 for LMR by ROC curves analysis. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), CSS and DFS, however, elevated LMR showed an adverse effect on worse OS, CSS and DFS. Multivariate analysis revealed that elevated dNLR was an independent factor for worse OS, and NLR was superior to dNLR, PLR and LMR in terms of hazard ratio (HR = 1.53, 95% CI = 1.11-2.11, P = 0.010), which was shown to be independent prognostic indicators for both CSS and DFS. Moreover, the nomogram could more accurately predict CSS (c-index: 0.89) and DFS (c-index: 0.84) in surgical GC patients.

          Conclusions

          Pre-operative NLR and dNLR may serve as potential prognostic biomarkers in patients with GC who underwent surgical resection. The proposed nomograms can be used for the prediction of CSS and DFS in patients with GC who have undergone gastrectomy.

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          Most cited references 33

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          7th edition of the AJCC cancer staging manual: stomach.

           M. Washington (2010)
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            Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests.

            We review the principles and practical application of receiver-operating characteristic (ROC) analysis for diagnostic tests. ROC analysis can be used for diagnostic tests with outcomes measured on ordinal, interval or ratio scales. The dependence of the diagnostic sensitivity and specificity on the selected cut-off value must be considered for a full test evaluation and for test comparison. All possible combinations of sensitivity and specificity that can be achieved by changing the test's cut-off value can be summarised using a single parameter; the area under the ROC curve. The ROC technique can also be used to optimise cut-off values with regard to a given prevalence in the target population and cost ratio of false-positive and false-negative results. However, plots of optimisation parameters against the selected cut-off value provide a more-direct method for cut-off selection. Candidates for such optimisation parameters are linear combinations of sensitivity and specificity (with weights selected to reflect the decision-making situation), odds ratio, chance-corrected measures of association (e. g. kappa) and likelihood ratios. We discuss some recent developments in ROC analysis, including meta-analysis of diagnostic tests, correlated ROC curves (paired-sample design) and chance- and prevalence-corrected ROC curves.
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              Recurrence following curative resection for gastric carcinoma.

              The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.
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                Author and article information

                Contributors
                qiw_deng@163.com
                1061851556@qq.com
                2697250365@qq.com
                jinjun_hou@163.com
                570154244@qq.com
                2339820358@qq.com
                sunhuiling1988@yeah.net
                tiany_gao@163.com
                18262638632@139.com
                love857_qiwendeng@163.com
                303794458@qq.com
                shukwang@163.com
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                18 February 2015
                18 February 2015
                2015
                : 13
                Affiliations
                [ ]Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006 China
                [ ]Department of Laboratory Medicine, Huai’an Second People’s Hospital, Huai’an, Jiangsu China
                [ ]Medical college, Southeast University, Nanjing, Jiangsu China
                [ ]Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu China
                [ ]Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu China
                [ ]Department of Orthopaedics, Lanxi People’s Hospital, Jinhua, Zhejiang China
                Article
                409
                10.1186/s12967-015-0409-0
                4343078
                © Deng et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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                Research
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                © The Author(s) 2015

                Medicine

                nomogram, inflammation, gastric cancer, prognosis, survival

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