Postoperative Prognosis Of Patients With Hepatocellular Carcinoma Evaluated By Serum IL-6Levels And Then Prognosis Index Was Established

Objective:Hepatocellular carcinoma is a high morbidity and mortality of cancer, liver resection is still the primary means of treatment of liver cancer at present.However, approximately70%hepatectomy in patients with recurrent or metastatic in five years. Exploring the predictors of recurrence of hepatocellular carcinoma, evaluating the prognosis of risks, judging the long-term survival is currently clinical attention and research hot spot.Previous studies suggest that the prognosis of hepatocellular carcinoma in patients not only related to the clinicopathological factors, but also related to potential serum cytokines levels. Through this study, IL-6levels before surgery and clinicopathological factors in patients with hepatocellular carcinoma were comprehensively analyzed,then to research intrinsically linked between IL-6levels and clinicopathological factors, discussing the main factors and independent factors of prognosis of HCC after hepatectomy.Finally establishing prognostic index and assessing comprehensively of long-term outcome after surgical treatment of hepatocellular carcinoma.Methods:A total of141cases of hepatocellular carcinoma cases who underwent surgical resection and met the inclusion criteria in general surgery department of the First Affiliated Hospital of Soochow University from July2007to June2010were selected, the application of enzyme-linked immunosorbent assay (ELISA method) was used to detect serum IL-6levels of patients with hepatocellular carcinoma before surgery, which meet the study criteria were128cases of patients selected for the study, and27cases selected as a control group of healthy adults, testing their serum IL-6levels. Mann-Whitney U test whether the differences between the two groups for further study.A retrospective analysis of128cases of clinical cases met the study criteria of their pathology, surgery, preoperative serum IL-6levels and other factors, with the life table method to calculate the cumulative survival and disease-free survival;Univariate survival analysis with Kaplan-Meier method plotted survival curves,the difference was significant by log-rank test for comparison.Multivariate analysis using multivariate COX proportional hazard model to select independent prognostic factors and to establish PI (prognostic index) which was evaluated by ROC curve. Statistical analysis were completed by SPSS19.0.Results:1.A preoperative serum IL-6in patients with hepatocellular carcinoma were significantly higher than in healthy adults, the difference was statistically significant (P <0.001).2.All cases’1,3,5-year cumulative survival rates were95.3%,61.9%and27.8%, with a median survival time of44.2months;1,2,3-year disease-free survival rates were84.1%,68.5%and49.3%, median survival time31.5months.Univariate analysis showed that preoperative6IL-serum, liver cirrhosis, AFP level, Child-Pugh grade, tumor size, number of tumors, violated the number of blood vessels, tumor capsular invasion, tumor differentiation, surgical margin, total liver blocking time was statistically significant of liver cancer prognosis (P values were less than0.05).3.Preoperative serum IL-6levels and clinicopathological factors which univariate analysis were significant were tested by X2test for linear trend indicate that serum levels of IL-6and AFP, tumor differentiation, tumor vascular invasion, tumor capsule invasion, surgical margin have linear trend relationship, however,it has wireless trends between the Child-Pugh grade and liver cirrhosis.Spearman rank correlation analysis showed that serum levels of IL-6was positively correlated with AFP, tumor vascular invasion, tumor capsular invasion and was negatively correlated with tumor differentiation,surgical margins, however,it has no correlation with cirrhosis of the liver and the Child-Pugh grade.4.Multifactor analysis of COX proportional hazard model found that the degree of tumor differentiation, tumor capsular invasion, violation of the number of blood vessels, AFP levels and serum IL-6levels were independent prognostic factors, the model was tested by the Wald test (x2=75.146, P=0.000) were statistically significant.Accordingly establish individual prognostic index PI=B0+0.946×tumor differentiation (Xi)+0.604×tumor vascular invasion (X2)+0.502×tumor capsular invasion (X3)+0.002×AFP (X4)+0.017×interleukin-6(X5), which Bo=-(0.946X1+0.604X2+0.502X3+0.002X4+0.017X5)=-6.156,ROC curve analysis:the area under the curve of0.927(95%CI:0.879-0.976), the best cutoff value of0.198(sensitivity90.89%specificity91.76%).Conclusions:(1) preoperative serum IL-6levels, AFP level, Child-Pugh classification, cirrhosis, tumor size, number of tumors, violated the number of blood vessels, tumor capsular invasion, tumor differentiation, surgical margin, total liver blocking time are the risk factors affected long-term survival of hepatocellular carcinoma after surgery,in which the degree of tumor differentiation, the number of violations of blood vessels, tumor capsular invasion, AFP levels, serum IL-6levels were independent risk factors for long-term survival.(2) Preoperative serum IL-6levels was correlated with the number of vascular invasion, tumor capsular invasion, tumor differentiation, AFP levels while it was not relevant with liver cirrhosis and Child-Pugh grade, suggesting that serum IL6levels should be the important serological performance of HCC tumor load or the degree of malignancy.(3) The individual prognostic index which contains preoperative serum IL-6levels and AFP levels to assess long-term postoperative survival of HCC is superior to the single AFP levels’assessment of the role.