Risk factors for cholangiocarcinoma.
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ABSTRACT:
SUBMITTER: Tyson GL
PROVIDER: S-EPMC3125451 | biostudies-literature | 2011 Jul
REPOSITORIES: biostudies-literature
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Risk factors for cholangiocarcinoma.
Tyson Gia L GL El-Serag Hashem B HB
Hepatology (Baltimore, Md.) 20110701 1
Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel ...[more]
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Project description:Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized.
| S-EPMC2504381 | biostudies-other
Project description:BackgroundCholangiocarcinoma (CCA) is a cancer arising from the intra- and extrahepatic bile ducts. The early stages are often asymptomatic, CCA is frequently diagnosed in an advanced stage and the prognosis of CCA is often dismal.ObjectiveOur objective was to estimate the incidence of CCA in Finland and to identify risk factors for CCA, with a special interest in primary sclerosing cholangitis (PSC).MethodsWe identified all CCA cases during 1974-2018 from the Finnish Cancer Registry and calculated age-standardised incidence rates. Five controls for each case were extracted from the Population Registry, matched by age, gender and municipality of residence at the time of diagnosis. Odds ratios (ORs) for risk factors were estimated with conditional logistic regression and survival estimates with the Kaplan-Meier method.ResultsIncidence of CCA remained stable in both genders; the age-standardised rate (World Standard) in 2013-2017 in males and females was 1.7 per 100,000 person years and 1.3 per 100,000 person years, respectively. Primary sclerosing cholangitis carried a 30-fold risk of intrahepatic cholangiocarcinoma (iCCA) and 25-fold risk of extrahepatic cholangiocarcinoma (eCCA). Diabetes, inflammatory bowel disease and liver cirrhosis were associated with iCCA, whereas cholelithiasis and viral hepatitis C were associated with eCCA. The cumulative 5-year survival was 4.6%.ConclusionsThe incidence of CCA has been stable. Known risk factors for CCA were confirmed, with PSC having the highest OR. Survival remains poor.
| S-EPMC8672081 | biostudies-literature
Project description:UnlabelledThe associations between diabetes, smoking, obesity, and intrahepatic cholangiocarcinoma (ICC) risk remain inconclusive. Metformin is purportedly associated with a reduced risk for various cancers. This case-control study evaluated risk factors for ICC and explored the effects of metformin on ICC risk in a clinic/hospital-based cohort. ICC patients observed at the Mayo Clinic (Rochester, MN) between January 2000 and May 2010 were identified. Age, sex, ethnicity, and residential area-matched controls were selected from among Mayo Clinic Biobank participants. The associations between potential factors and ICC risk were determined. Six hundred and twelve cases and 594 controls were identified. Factors associated with increased ICC risk included biliary tract diseases (adjusted odds ratio [AOR]: 81.8; 95% confidence interval [CI]: 11.2-598.8; P < 0.001), cirrhosis (AOR, 8.0; 95% CI: 1.8-36.5; P = 0.007), diabetes (AOR, 3.6; 95% CI: 2.3-5.5; P < 0.001), and smoking (AOR, 1.6; 95% CI: 1.3-2.1; P < 0.001). Compared to diabetic patients not treated with metformin, the odds ratio (OR) for ICC for diabetic patients treated with metformin was significantly decreased (OR, 0.4; 95% CI: 0.2-0.9; P = 0.04). Obesity and metabolic syndrome were not associated with ICC.ConclusionThis study confirmed diabetes and smoking as independent risk factors for ICC. A novel finding was that treatment with metformin was significantly associated with a 60% reduction in ICC risk in diabetic patients.
| S-EPMC3565026 | biostudies-literature
Project description:BackgroundCombined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC.MethodsThe study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell's C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models.ResultsThe overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% (P > 0.05). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria (P=0.022 and P=0.015). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria (P=0.340).ConclusionThe morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.
| S-EPMC8683178 | biostudies-literature
Project description:Background: Several risk factors have been identified for CCA, however, whether such associations were causal remains unknown. Methods: Mendelian randomization (MR) has been applied to examine the causal relationship between 26 putative risk factors and CCA. The genetic variants for each risk factor were extracted from their corresponding genome-wide association study (GWAS) if they reached the genome-wide significance (p-value < 5 × 10-8). The genetic associations with CCA were obtained from the publicly available GWAS with the largest sample size. Mainly, inverse-variance weighted (IVW) has been adopted to estimate the causal effect on CCA. Both multivariable and mediation MR analyses were carried out to detect independent factors. Results: Three putative risk factors can causally elevate the risk of CCA after FDR correction, including liver fat content (LFC), non-alcoholic fatty liver disease (NAFLD), and cholelithiasis. The odds of CCA would increase per 1-SD increase in the liver fat content (LFC) (OR = 2.12 [1.66, 2.71]) and logOR of NAFLD. The genetic liability to cholelithiasis would increase the risk of CCA as well (OR = 2.17 [1.47, 3.20]). They were still significant in other methods. The multivariable MR analysis indicated that genetically-elevated LFC should increase the risk of CCA independently of cholelithiasis (OR = 1.88 [1.39, 2.55]). In the mediation MR analysis, the indirect effect was not significant when treating cholelithiasis as the mediator (indirect OR = 0.95 [0.85, 1.07]). Conclusion: This MR study identified that gallstone and liver fat accumulation are two independent risk factors of CCA, suggesting two modifiable ways of preventing CCA.
| S-EPMC9462706 | biostudies-literature
Project description:BackgroundEarly recurrence after curative resection of perihilar cholangiocarcinoma (PHCC) often occurs within a year of surgery. Preoperative predictors of early recurrence remain unclear. The aim of this study was to define reliable preoperative predictors of early recurrence.MethodsMedical records and preoperative multidetector-row CT of patients with PHCC who underwent resection between 2002 and 2018 were reviewed. Clinical findings, tumour markers, and radiological appearances including a 'periductal enation sign' (PES) where there was evidence of soft tissue enhancement appearing to arise from the extrahepatic bile duct, were analysed.ResultsAmong 261 patients who underwent resection for PHCC, 67 (25.7 per cent) developed early recurrence. Multivariable analysis identified four preoperative risk factors for early recurrence, namely carbohydrate antigen 19-9 (CA19-9) 37 U/ml or higher (OR 2.19, 95 per cent confidence interval (c.i.) 1.08 to 4.46), positive PES (OR 7.37, 95 per cent c.i. 2.46 to 22.10), mass-forming tumour (OR 4.46, 95 per cent c.i. 1.83 to 10.90), and luminal-occlusion tumour (OR 4.52, 95 per cent c.i. 2.11 to 9.68). The OR of preoperative risk factors were used to define four risk subgroups for early recurrence. The early recurrence rates in the low, moderate, high, and very-high risk groups were 0, 9.4 , 39.7, and 65.0 per cent respectively.ConclusionCA19-9, PES, mass-forming tumour, and luminal-occlusion tumour identify patients at higher risk for early recurrence after resection of PHCC.
| S-EPMC9487653 | biostudies-literature
Project description:BACKGROUND: Cholangiocarcinoma, including intra- and extrahepatic cholangiocarcinoma, is a rare but highly lethal cancer. Despite effort in finding the risk factors of cholangiocarcinoma, the causes of most cholangiocarcinoma remain unknown. This study utilized a population-based case-control design using data from the National Health Insurance Research Database (NHIRD) of Taiwan to assess the medical conditions associated with cholangiocarcinoma. METHODS: 5,157 incident cases of cholangiocarcinoma diagnosed during 2004 to 2008 and 20,628 controls matched to the cases on sex, age, and time of diagnosis (reference date for the controls) were identified from the NHIRD. Medical risk factors were ascertained from the NHIRD for each individual. Conditional logistic regression was performed to evaluate the association between cholangiocarcinoma and each medical risk factor. RESULTS: The results showed that factors associated with an increased risk of cholangiocarcinoma included cholangitis, cholelithiasis, cholecystitis, cirrhosis of liver, alcoholic liver disease, chronic non-alcoholic liver disease, hepatitis B, hepatitis C, diabetes, chronic pancreatitis, inflammatory bowel disease, and peptic ulcer. In addition, sex and age differences were observed. CONCLUSIONS: This study confirms the association between cholangiocarcinoma and several less established risk factors, including diabetes, inflammatory bowel disease, hepatitis B, hepatitis C, and peptic ulcer (proxy for the presence of Helicobacter Pylori). Future studies should focus on finding additional environmental and genetic causes of cholangiocarcinoma.
| S-EPMC3718690 | biostudies-other
Project description:Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382-2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061-2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095-2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120-2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367-2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331-2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409-2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.
| S-EPMC6737003 | biostudies-literature
Project description:Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions.We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated.Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias.Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.
| S-EPMC3804834 | biostudies-literature
Project description:BackgroundThis study explores molecular features associated with better prognosis in cholangiocarcinoma (CCA).Methods and resultsThe transcriptomic and whole-exome sequencing data obtained from paired tissues of 70 were analyzed, grouping them based on progression-free survival (PFS), differentiation degree, and lymph node metastasis. Among the 70 patients, the TP53 gene mutation frequency was the highest (53%), while FLG gene mutation occurred exclusively in the long PFS group. In the comparison between long and short survival groups, the short PFS group exhibited higher monocyte infiltration levels (p = 0.0287) and upregulation of genes associated with cancer-related transcriptional misregulation, chemokine signaling, and cytokine-cytokine receptor interactions. Differences in immune cell infiltration and gene expression were significant across differentiation and lymph node metastasis groups. Particularly noteworthy was the marked increase in CD8 T cell and NK cell infiltration (p = 0.0291, 0.0459) in the lymph node metastasis group, significantly influences prognosis. Additionally, genes related to platinum resistance, Th17 cell differentiation, and Th1 and Th2 cell differentiation pathways were overexpressed in this group. In summary, higher monocyte infiltration levels in the short PFS group, along with elevated expression of genes associated with cancer-related pathways, suggest a poorer prognosis. The significant increase in CD8 T cell and NK cell infiltration reflects an enhanced anti-tumor immune response, underscoring the relevance of immune infiltration levels and gene expression in predicting outcomes for CCA patients.ConclusionsIn this study, we elucidated the pertinent molecular mechanisms and pathways that influence the prognosis of CCAs through comprehensive multi-omics analysis.
| S-EPMC11358702 | biostudies-literature