Risk Factors And Carcinogenesis Of Intrahepatic Cholangiocarcinoma

PARTⅠRisk Factors of Intrahepatic Cholangiocarcinoma:A Case-control StudyBackground & aims:Intrahenatic cholangiocarcinoma (ICC) is the most common malignant tumor of the liver after hepatocellular carcinoma (HCC). The risk factors for ICC are poorly understood in China. Herein, we explore the potential risk factors of intrahepatic cholangiocarcinoma(ICC) in China, so as to establish evidence basis for the prevention and treatment of ICC.Methods:A case-control studv including 317 patients with ICC confirmed by pathological examination and 634 non-cancer healthy individuals was conducted. The cases and controls were matched in age, sex and inhabitancy. Data were analyzed by statistical technique of Chi-square test and conditional logistic regression.Results:Univariate analvsis showed that HBsAg seropositivitv. liver cirrhosis (cirrhosis related to HBV infection, alcohol and else causes), hepatolithiasis, choledocholithiasis and schistosomiasis had significant differences between the 2 groups (P<0.05). Multivariate analysis confirmed that HBsAg seropositivity, liver cirrhosis related to HBV infection, alcoholic cirrhosis, cirrhosis due to other causes, hepatolithiasis and hepatic schistosomiasis were still significantly related to ICC, and their adjusted odds ratio (95% confidence interval) were 10.265 (6.676-15.783),13.101 (5.265-32.604),18.242 (3.580-92.958),18.435 (1.930-176.082),15.102 (4.607-49.499) and 11.820 (3.522-39.668), respectively. The incidence of hepatic cyst, cholecystolithiasis, hepatic haemangioma, fatty liver, diabetes mellitus, smoking and drinking were not significant difference between cases (ICC) and controls.Conclusions:The HBV infection. liver cirrhosis (mainlv related to HBV infection). hepatolithiasis and hepatic schistosomiasis may be potential risk factors for ICC in China. The incidence of HBV infection in ICC patients is very higher in China than in other countries reported. PARTⅡHepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesisBackground and aims:Intrahenatic cholangiocarcinoma (ICC) a malignant tumour arising from peripheral intrahepatic bile duct epithelium. Recent studies and data from our former studies suggeste hepatitis B virus (HBV) infection is possible risk factor of ICC. The carcinogenesis of ICC remains unclear. To understand the pathogenesis of ICC, we analyzed clinicopathologic characteristics of ICC patients with seropositive hepatitis B surface antigen (HBsAg).Methods:A retrospective case-control studv was conducted. Cases were 317 ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in China between 2003 and 2006. Among 317 consecutively enrolled ICC patients,154 patients were seropositive HBsAg (48.6%). We compared clinicopathologic characteristics of these patients (groupⅠ) with ICC patients seronegative for HBsAg (groupⅡ; n=163) and compared the age and sex distributions of patients in group I with randomly selected HBV-associated hepatocellular carcinoma (HCC)(groupⅢ; n=1140).Results:Compared with seronegative-HBsAg ICC patients. seropositive-HBsAg ICC patients were younger, more frequently male and had a higher proportion of abnormal aminotransferase and serum alpha-fetoprotein (AFP) level, histological inflammation and cirrhosis, right lobe focus, poor tumour differentiation, tumour encapsulation and microvascular invasion; had a lower proportion of abnormal serum carbohydrate antigen 19-9 (CA19-9) level and lymphatic metastasis. The age and sex distribution profiles were nearly identical between seropositive-HBsAg ICC patients and HBV-associated HCC patients.Conclusions:HBV-associated ICC shares manv clinicopathological similarities with HBV-associated HCC. The result indicated HBV-associated ICC and HBV-associated HCC may hold common disease process for carcinogenesis.PARTⅢHepatitis B virus infection:a favorable prognostic factor after resection of intrahepatic cholangiocarcinomaBackground and aims:Hepatitis B virus (HBV) infection is known risk factor for the development of intrahepatic cholangiocarcinoma (ICC). The impact of HBV infection on survival of ICC patients is still unclear. The aims of this study were to investigate the prognostic factors of ICC and evaluate the impact of chronic HBV infection on survival.Methods:A retrosnective studv was conducted with a total of 155 patients who underwent hepatectomy resulted in macroscopic curative resection (R0 and R1). The patients were classified according to the status of chronic HBV infection (represented by positive HBsAg (hepatitis B surface antigen) in serum or liver tissue). Cliniccpathological characteristics and survival were reviewed.Results:All natients underwent anatomical resection The 1-vear and 3-vear survival rates were 60.6% and 32.1%, respectively. Multivariate analysis revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were independent prognostic factors on survival. Median disease-free survival time was 5.0 months. Multiple tumour, microscopic satellite lesion, and vascular invasion were independent prognostic factors for disease-free survival. The prognostic factors affecting survival in ICC patients with HBV infection (groupⅠ) and without HBV infection (groupⅡ) were not completely consistent. The independent poorer prognostic factors in groupⅠwere ALP (alkaline phosphatase), microscopic satellite lesion, vascular invasion, and lymphatic metastasis, while the independent poorer prognostic factors in groupⅡwere r-GT (r-glutamyltransferase), microscopic satellite lesion, and tumour poor differentiation.Conclusions:Our results suggest absence of HRV infection in ICC was a valuable clinical factor for predicting clinicopathologic invasiveness and clinical outcome. ICC Patients with HBV infection should be distinguished from other ICC patients, because of their different clinicopathological characteristics, prognostic factors and favourable outcome after surgical resection.PART IVEtiological and clinicopathologic characteristics of intrahepatic cholangiocarcinoma in young patientsBackground and aims:Intrahepatic cholangiocarcinoma (ICC is the most common malignant tumor of the liver, after hepatocellular carcinoma (HCC). Although several risk factors have been associated with the development of ICC, such as viral infection (hepatitis B virus (HBV) and hepatitis (HCV)), the risk factors and clinicopathologic features of young ICC patients have not been fully studied. In the present study, we investigated the prevalence, risk factors, and clinicopathologic characteristics of ICC in young patients.Methods:A retrospective analvsis was performed for ICC natients referred to the Eastern Hepatobiliary Surgery Hospital in China. Among 317 consecutively enrolled patients,40 patients were≤40 years old (12.61%). We compared the risk factors and clinicopathologic characteristics of these patients with ICC (group I) to those of patients> 40 years old (group II; n= 277).Results:GroupⅠhad distinct features compared to groupⅡ. such as:a low freauencv of hepatolithiasis (P<0.001); a high positive rate of serum hepatitis B surface antigen (HBsAg) (P<0.001) and hepatitis B virus (HBV)-associated cirrhosis (P=0.038); a high frequency of a-fetoprotein (>400ng/mL) (P=0.011); a low frequency of carbohydrate antigen 19-9 (> 37 U/mL) (P=0.017); and a high frequency of liver histological inflammation (P=0.002). Although there was no significant difference between the two groups in regards to hepatic schistosomiasis, alcohol-associated cirrhosis and cirrhosis due to other causes (P>0.05), they only occurred in the elder group.Conclusions:The results suggest that the risk factors are significantlv different for young and elder ICC patients. HBV and HBV-associated cirrhosis are the most important risk factors for young ICC patients. PARTⅤAntibodies to Hepatitis B virus and Intrahepatic Cholangiocarcinoma:A case-control StudyBackground and aims:To explore the association between antibodv to hepatitis B surface antigen (anti-HBs), antibody to core antigen (anti-HBc) and antibody to e antigen (anti-HBe) and intrahepatic cholangiocarcinoma, so as to establish evidence basis for the prevention and treatment of ICC.Methods:A case-control studv including 113 TCC patients with seronegative HRsAg (hepatitis B surface antigen) confirmed by pathological examination and 226 non-cancer healthy individuals (seronegative HBsAg) was conducted. The cases and controls were matched in age, sex and inhabitancy. Data were analyzed by statistical technique of Chi-square test and conditional logistic regression.Results:Univariate analvsis showed that anti-HBs. anti-HBe and anti-HBc seronositivitv had significant differences between the 2 groups (P<0.05). Multivariate analysis confirmed that anti-HBs, anti-HBe and anti-HBc seropositivity were still significantly related to ICC. Anti-HBs seropositivity displayed negative correlation and its adjusted odds ratio (95% confidence interval,95%CI) was 0.542 (0.326-0.902); Anti-HBe and anti-HBc positivity displayed positive correlation and their adjusted odds ratio (95% confidence interval) was 2.244 (1.070-4.705) and 4.050 (2.141-7.663), respectively.Conclusions:Anti-HBs. anti-HBc and anti-HBe nositive results on serologic testing were significant differences between ICC patients and healthy individuals. The results suggest previous exposure to hepatitis B virus (HBV) or occult HBV infection may have an important role in the development of ICC.