The Etiology And Prognostic Staging System Of Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a malignancy arising from the endothelial cells of secondary bile duct and upper braches of intrahepatic bile duct, and accounted for 5-30% in all primary hepatic malignant tumors, with a incidence rate only inferior to that of hepatic cellular cancer (HCC). A study reported that the morbidity and mortality had an ascending tendency in recent years. At present, the hepatectomy for early ICC is preferable therapeutic method, but with a very high recurrence and postoperative 5-year survival rate as 20-40%. ICC has a distinctive pathogenesis and oncobiological characteristics, and because it derives from the endothelial cells of bile duct, there are significant differences between ICC and HCC regarding the pathological presentation of tumor. Although the overall pathological appearance and infiltrating mode of ICC are similar to that of extrahepatic cholangiocarcinoma, thus, the study on ICC, in which, ICC is defined as an independent malignant disease, is a current development tendency; the independent analysis of ICC in AJCC 7th TNM staging was also in accordance with the tendency and understanding of ICC.Based on the data deriving from ICC patients in Chinese mainland, this study aims to establish a prognostic staging system which is applicable for ICC patients who underwent the hepatectomy, and to determine which kind of staging system can more accurately predict the surgical outcome of patients with ICC by the comparison among various reported ICC staging system.The main results are as follows:1. In the training set, the multivariate analysis showed that serum carbohydrate antigen 19-9 (CA19-9),γ-glutamyltransferase, tumor size and number, vascular invasion were the independent risk factors for postoperative recurrence of ICC. Additionally, carcinoembryonic antigen (CEA), lymph node metastasis and extrahepatic metastasis were also the independent risk factors for postoperative survival of patients with ICC. In 367 patients, the 5-year survival rates at stage A, B, C were 59.7%, 35.8%, 6.7% respectively.2. The comparison of prognostic predictive capability among each stage was performed in the verification group, and the prognostic predictive capability of EHBH staging system was more favorable.3. Comparison of predictive value between the EHBH staging system and single risk factor: Tumor size and number was the risk factor which accounted for the highest weight proportion in the EHBH prognostic risk scoring system, and its risk score of overall survival of ICC patients can be up to 2 points respectively and4 points, and its risk score of neoplasm recurrence can reach 3 points and 4 points. We compared the predictive capability for the prognosis of ICC between this staging system and single factor, and found out that the areas under the curve of overall survival of the two were 0.80 (EHBH; 95% CI, 0.75-0.84) and 0.69 (tumor size and number; 95% CI, 0.65-0.75), respectively and there were significant differences between the two (P=0.015). The areas under the curve of recurrence were 0.70 (EHBH; 95% CI, 0.64-0.75) and 0.63 (tumor size and number; 95% CI, 0.58-0.69) respectively, and there were remarkable differences between the two (P=0.027). Through such comparisons, we found that the staging system which was established with a system including all the risk factors had more value than a single factor for the prediction of prognosis. 4. By logistic regression analysis showed that the main cause of the development of ICC are: virus infection (HBV), alcohol, bile duct inflammation, diabetes, and there is a link between causes: virus infection and alcohol consumption as well as synergies between the bile duct inflammation relationships, and its Synergy index were 1.2,5.6. The cause of the population due to tumor incidence: the virus infected 52%, 12% alcohol, 16% of biliary tract inflammation, diabetes 10%.In conclusion, the present study demonstrated as follows :1. Serum carbohydrate antigen 19-9 (CA19-9),γ-glutamyltransferase, tumor size and number, vascular invasion were the independent risk factors for postoperative recurrence of ICC. Additionally, carcinoembryonic antigen (CEA), lymph node metastasis and extrahepatic metastasis were also the independent risk factors for postoperative survival of patients with ICC.2. The comparison of prognostic predictive capability among each stage was performed in the verification group, and the prognostic predictive capability of EHBH staging system was more favorable.3. In conclusion, the significant synergy between hepatitis virus infection, alcohol consumption, and biliary tract inflammation may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new ICC prevention strategies in highrisk individuals.