Prgonostic Analysis Of Liver Resection For Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy arising from the endothelial cells of secondary bile duct and upper braches of intrahepatic bile duct, and accounts for 5-30% in all primary hepatic malignancies, with its incidence rate only second to that of hepatocellular carcinoma (HCC). Worldwide, the morbidity and mortality of ICC had an ascending tendency in recent years and liver resection remains the first-line therapy for ICC. Firstly, in this study, the overall postoperative prognosis of ICC patients who underwent liver resection and risk factors which impact the prognosis were analyzed. Secondly, the risk factors for early recurrence were identified, because ICC exhibits more aggressive behaviour, and more likely occurrs early metastases when compared with HCC. Thirdly, the outcomes of ICC patients with cirrhosis were studied, because HBV infection is one of major causative factors for ICC in China. Finally, the role of adjuvant TACE in improving the prognosis of was evaluated, since there was so far no effective anti-recurrence treatment.Part I. Analysis of the Postoperative Prognosis of ICC PatientsThe overall postoperative prognosis of ICC patients who underwent liver rection and the independent prognostic factors were analyzed.A total of 1370 ICC patients following hepatectomy between January 2005 to December 2012 at the Eastern Hepatobiliary Surgery Hopital were included, and the follow-up was censored on December 2014. The recurrent and survival rates were analyzed by Kaplan-Meier method and compared by Log-rank test. Cox proportional hazards model was used to identify the independent prognostic risk factors.In the whole cohort, the median overall survival (OS) was 26.1 months, and the 1-, 3-and 5-year OS rates were 68.0%,41.9% and 32.5%, respectively. The median time to recurrence (TTR) was 16.2 months and the postoperative 1-,3-and 5-year recurrence rates were 42.8%,67.5% and 75.4%. Multivariable analysis showed that CA19-9, tumor diameter, multiple tumors, lymph node metastasis, vascular invasion and local invasion were independent risk factors for both TTR and OS, while CEA was an additional independent risk factor for OS.The postoperative prognosis of ICC patients is poor. In addition to the traditional tumor stage factors, the level of serum tumor markers is also very important for the prognosis of ICC. Also, the large tumor size and local invasion decrease the surgical effectiveness.Part II. Risk Factors for Early Recurrence in ICC Patients following Liver ResectionThe recurrence which occured within 1 year after surgery was identified as early recurrence. The clinicopathological characteristics of patients with early recurrence were described and the risk factors for early recurrence were analyzed. Furthermore, a scoring system based on the independent prognostic factors was established to identify those patients who had high risk of early recurrence.Using Kaplan-Meier method, the early recurrence rates of ICC patients in whole cohort was calculated. The related risk factors were conformed by Cox proportional hazards model. Based on the beta coefficient of each risk factor, a scoring system was established.The early recurrence rate in the whole cohort was 42.8%. Multivariable analysis showed that tumor diameter, multiple tumors, lymph node metastasis, vascular invasion and local invasion were independent risk factors for early recurrence. When the point of each risk factor was defined as 1, recurrence rates among patients in high score group (3-5 points), middle score group (1-2 points) and low score group (0 point) were significantly different (P<0.001), and the early recurrence rate of patients in the low score group was the lowest.Patients with more independent risk factors of early recurrence are more easily to have recurrence within 1 year after surgery. Our scoring system can serve as a tool to identify high risk patients.Part III. Postoperative Outcomes of ICC Patients with CirrhosisThe prognosis between ICC patients with and without cirrhosis was compared. In cirrhotic patients, the impact of portal hypertension on surgical outcome was analyzed.The incidence of surgical complications was depicted to analyze the short term outcome of ICC patients with cirrhosis. And then, the overall survival and recurrent rates were reported to show the long term prognosis. In ICC patients with cirrhosis, the same analyses were performed according to the status of portal hypertension.Compared with the patients without cirrhosis, patients with cirrhosis had a higher incidence rate of surgical complications (P=0.047), however, there was no significant differences in OS (P=0.263) and recurrence (P=0.387) between these two groups. In patients with portal hypertension, the 5-year OS and recurrence rate were 30% and 76%, which were worse than those of patients without portal hypertension (40% for OS,67% for recurrence rate, P=0.040 for OS, P=0.021 for recurrence).If the indiction could be well complied with, liver resection should also be recomended to the ICC paitents with cirrhosis. However, the portal hypertension is a contradication for these patients if the hepatectomy would be considered.Part IV. Adjuvant TYansarterial Chemoembolization Following Liver Resection for ICC PatientsThe established prognostic nomogram (ICC-nomogram) was used to perform the survival risk stratification, and then the patients who could benefit from adjuvant TACE were identified.The study population and analysis of recurrence and OS are the same as the parts mentioned above. The analysis by the ICC-nomogram followed previous report. With the use of (propensity score matching, PSM), the significant differences in baseline characteristics between these with or without adjuvant TACE patients were adjusted.The 1-,3- and 5-year OS rates in the TACE group were 78.9%,45.0% and 37.0%, respectively, which was significantly higher than those in the non-TACE group (64.9%, 41.1% and 31.2%, respectively, P=0.006). The 1-,3- and 5-year recurrence rates in the TACE group were 38.3%,65.4% and 68.9%, respectively, which were significantly lower than those in the non-TACE group (44.1%,68.0% and 77.6%, respectively, P=0.008). After a 1:1 PSM, a cohort with 303 patients each in the TACE and the non-TACE groups was obtained. There were no significant differences in the OS rates (P=0.854) and recurrence rates (P=0.300) between these two groups. Survival stratification was then carried out by stratifying patients into three groups based on scores as calculated by the ICC-nomogram. Accordingly,458 patients were divided into the tertile with good prognosis,456 patients into the tertile with middle prognosis and 456 patients into the tertile with poor prognosis. There were no significant differences in the OS rates (P=0.156, P=0.215) and recurrence (P=0.201, P=0.194) between the TACE and non-TACE groups in the tertile with good and middle prognosis. For patients in the tertile with poor prognosis, adjuvant TACE could significantly improve the prognosis (P=0.001 for OS; P=0.007 for recurrence).Adjuvant TACE following liver resection for ICC might only benefit the patients with poor prognosis (with high nomogram scores).