Survival Analysis Of Intrahepatic Cholangiocarcinoma Patients Following Surgical Resection And Analysis Of Expression And Clinical Significances Of Beclin 1,ARID1A,IDH1 And CA9

Part I Survival analysis of 123 intrahepatic cholangiocarcinoma patients following surgical resection[Objective] To investigate the prognostic factors of intrahepatic cholangiocarcinoma following surgical resection.【Methods】 Clinical and pathological data of 123 patients who underwent surgical resection for intrahepatic cholangiocarcinoma between January 1999 and June 2015 in our hospital was collected. Survival rate was calculated with Kaplan-Meier method. The Log-rank method was used for comparing survival curves. Correlation between clinicopathological factors was analysed with Chi-square test or Fisher’s exact test. Cox regression model was used for multiple factors analysis.【Results】 Median follow-up time of 123 patients was 22 months and median recurrence-free survival time was 9.0 months.One year,2 years and 3 years recurrence rate were 58.6%,68.9% and 76.5%. Univariate analysis revealed that factors associated with postoperative recurrence-free survival were preoperative laboratory test results of GGT, ALP and CEA, surgical margin, numbers of lesions, maximum diameter of tumor,lymph node metastasis, invasion of extrahepatic tissues,invasion of nerves, necrosis and mucus(P<0.05). Cox multivariate analysis revealed that preoperative rise in CEA, lymph node metastasis, multiple lesions, invasion of extrahepatic tissues and necrosis of the tumor were significant adverse prognostic factors of postoperative recurrence-free survival(P<0.05). Median overall survival time was 21.2 months. One year,3 years and 5 years overall survival rate were 76.6%,33.2% and 26.1%. Univariate analysis revealed that factors associated with postoperative overall survival were preoperative laboratory test results of GGT, ALP and CEA, surgical margin, numbers of lesions, maximum diameter of tumor,lymph node metastasis, invasion of extrahepatic tissues,invasion of nerves,necrosis and mucus(P<0.05). Cox multivariate analysis revealed that preoperative rise in CEA, lymph node metastasis, multiple lesions and invasion of extrahepatic tissues were significant adverse prognostic factors of postoperative overall survival(P<0.05). All 123 cases were then divided into two groups with normal and high CEA.Futher analysis revealed that preoperative rise in ALP was also a significant adverse prognostic factor of postoperative recurrence-free survival and overall survival for normal CEA group.For high CEA group,multiple lesions may be the significant adverse prognostic factor of postoperative recurrence-free survival,and invasion of liver capsule may be the significant adverse prognostic factor of postoperative overall survival.[Conclusion] Preoperative rise in CEA, lymph node metastasis, multiple lesions and invasion of extrahepatic tissues were significant adverse prognostic factors of postoperative recurrence-free survival and overall survival for intrahepatic cholangiocarcinoma patients who underwent surgical resection. For patients with normal CEA, preoperative rise in ALP was also a significant adverse prognostic factors of postoperative recurrence-free survival and overall survival.PartⅡ Expression and clinical significances of Beclin 1,ARID1A,IDH1 and CA9 in intrahepatic cholangiocarcinoma【Objective】 To investigate expression and clinical significances of Beclin 1,ARID1A,IDH1 and CA9 in intrahepatic cholangiocarcinoma[Methods] Based on data of clinical research of 123 cases,we seclected 113 well-preserved paraffin-embedded specimens. Through immunohistochemical staining method, we check expression of Beclin 1,ARID1A,1DH1 and CA9,and then further analyze the correlation between immunohistochemical results,clinicopathological factors and prognosis.[Results] For Beclin 1,48 samples presented low expression while 65 samples presented high expression. For ARID1A,36 samples presented negative expression while 77 samples presented positive expression. For IDH1,8 samples presented negative expression while 105 samples presented positive expression. For CA9,17samples presented negative expression while 96 samples presented positive expression. Expression of Beclin 1 was correlated with maximum diameter of tumor. ARID 1A was correlated with invasion of extrahepatic tissues..IDH1 was correlated with preoperative CA19-9. CA9 was correlated with lymph node metastasis and invasion of nerves. Median recurrence-free survival time of 113 patients was 9.0 months. One year,2 years and 3 years recurrence rate were 59.4%,69.8% and 77.2%, respectively. Univariate analysis revealed that factors associated with postoperative recurrence-free survival were the expression levels of Beclinl and ARID1A, preoperative laboratory test results of GGT, ALP and CEA, surgical margin, numbers of lesions, maximum diameter of tumor,lymph node metastasis, invasion of extrahepatic tissues, necrosis and mucus(P<0.05). Median overall survival time was 20.3 months,1 year,3 years and 5 years overall survival rate were 75.4%,30.8% and 23.3%, respectively.Univariate analysis revealed that factors associated with postoperative overall survival were the expression level of Beclin 1,preoperative laboratory test results of GGT,ALP and CEA, surgical margin,numbers of lesions, maximum diameter of tumor,lymph node metastasis, invasion of extrahepatic tissues,invasion of nerves,macroscopic type and mucus(P<0.05).The expression levels of Beclin 1 and ARID1A were positive correlated.Cox multivariate analysis revealed that high expression of Beclin 1 and positive expression of ARID1A both were significant adverse prognostic factors of postoperative recurrence-free survival and overall survical(P<0.05).Expression of IDH1 and CA9 were not correlated with postoperative recurrence-free survival and overall survical【Conclusion】 High expression of Beclin 1 and positive expression of ARID 1A both were significant adverse prognostic factors of postoperative recurrence-free survival and overall survical in patients with intrahepatic cholangiocarcinoma after surgical resection.