Incidence Of Extrahepatic Cholangiocarcinoma Research Articles

New epidemiologic trends in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy and the second most frequent primary hepatic malignancy after hepatocellular carcinoma. During the past three decades, the incidence of intrahepatic cholangiocarcinoma (iCCA) has risen in Western Europe, while the incidence of extrahepatic cholangiocarcinoma (eCCA) has remained stable or fallen. The mortality rates of iCCA, which are greater than those of eCCA, showed also an increasing trend, while those of eCCA remained stable. Well-known risk factors like hepatobiliary flukes, hepatolithiasis and choledochal cysts are important in the development of iCCA particularly in Asian countries. In Western countries, the primary sclerosing cholangitis is the most common risk factor for CCA. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cirrhosis are considered to be risk factors for iCCA. Emergent risk factors such as obesity, diabetes and MAFLD are increasingly associated mostly with iCCA.

Intrahepatic Cholangiocarcinoma: Evolving Concepts and Medical Treatment

Cholangiocarcinoma (bile duct cancer) is classified into intrahepatic and extrahepatic cholangiocarcinoma (perihilar and distal cholangiocarcinoma) according to the anatomical location of the lesion. The incidence of extrahepatic cholangiocarcinoma has been relatively stagnant in recent decades, but intrahepatic cholangiocarcinoma is steadily increasing worldwide, requiring attention. Various classification systems based on gross growth patterns, histological findings, and tumor-derived cells, as well as classification based on existing anatomical location, have been proposed, however, the consensus has not been established yet. Intrahepatic cholangiocarcinoma is a carcinoma with an extremely poor prognosis. Complete tumor resection is the only curative treatment. The overall survival rate for 5 years after surgery is 15% to 40%, but recurrence after surgery is observed in 2/3 patients. Therefore, determining the right stage before surgery and selecting an appropriate treatment method through a multidisciplinary approach is a very important process in determining proper treatment. Systemic therapy may be used for locally advanced biliary tract cancer or metastatic biliary tract cancer where surgery is not possible. However, the effectiveness of traditional anticancer chemotherapeutic agents is rather pessimistic, therefore treatments using molecular biological properties have recently been attempted. Finding a way to increase the number of resectable cases through early diagnosis is one of the main challenges. In addition, it is also hoped that the selection of new therapeutic targets and therapeutics will be possible as a result of advanced research on gene expression profiles and mutations in cholangiocarcinoma.

Transcriptome analysis reveals dysregulated long non-coding RNAs and mRNAs associated with extrahepatic cholangiocarcinoma progression.

The incidence of extrahepatic cholangiocarcinoma (ECC) is the highest of all the cholangiocarcinoma cases. However, the molecular mechanism of ECC genesis and progression remains unclear. Long non-coding RNAs (lncRNAs) have been revealed to perform critical regulatory roles in cancer biology. In order to understand lncRNA expression patterns and their potential function in ECC, a transcriptome analysis of lncRNA and mRNA expression was performed in ECC and paired adjacent non-cancerous tissues using Agilent human lncRNA + mRNA arrayV4.0 (4×180 K format). It was identified that 268 lncRNAs and 459 mRNAs were differentially expressed in ECC. Among these, 78 lncRNAs and 66 mRNAs were upregulated >2-fold compared with adjacent non-cancerous tissues, and 190 lncRNAs and 393 mRNAs were downregulated in the ECC samples. Differences in lncRNA expression between ECC and paired adjacent non-cancerous tissues were confirmed using reverse transcription-quantitative polymerase chain reactionas proof of principle. Functional analysis of co-expressed mRNAs with lncRNAs indicated that these dysregulated lncRNAsmay be involved in known ECC-associated biological processes and pathways. The present findings indicated that mRNAs and lncRNAs perform important roles in the development and progression of ECC. The present findings may lay the foundation for future efforts to understand the role of lncRNAs and develop novel biomarkers in ECC.

Predictive Factors of Biliary Tract Cancer in Anomalous Union of the Pancreaticobiliary Duct.

The assessment of malignancies associated with anomalous union of the pancreaticobiliary duct (AUPBD) is essential for the design of appropriate treatment strategies. The aim of the present study is to measure the incidence of AUPBD-related pancreaticobiliary malignancy and to identify predictive factors. This retrospective cohort study included cases of 229 patients with AUPBD between January 1999 and December 2013. The impact of bile duct dilatation on the incidence of AUPBD-related pancreaticobiliary disease was measured, and predictive factors were evaluated.Among 229 patients with AUPBD, 152 had common bile duct dilatation (≥10 mm) (dilated group) and 77 did not (<10 mm) (nondilated group). Intrahepatic cholangiocarcinoma occurred more frequently in the nondilated group than in the dilated group (3.9% vs 0%; P < 0.05). By contrast, no significant difference in the incidence of extrahepatic cholangiocarcinoma was observed between the 2 groups (1.3% vs 3.9%; P = 0.271). By univariate analysis, age, type of AUPBD, and the level of pancreatic enzymes refluxed in the bile duct were associated with occurrence of biliary tract cancers. In multivariate analysis, age ≥45 years (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.011–1.073, P < 0.05), P-C type (OR 3.327, 95% CI 1.031–10.740, P < 0.05), and a high level of biliary lipase (OR 4.132, 95% CI 1.420–12.021, P < 0.05) showed a significant association with AUPBD-related biliary tract cancer.Intrahepatic cholangiocarcinoma may occur more frequently in AUPBD patients without bile duct dilatation. Age ≥45 years, P-C type, and biliary lipase level ≥45,000 IU/L are significantly associated with AUPBD-related biliary tract cancer.

Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis.

Secular Trends in the Incidence of Cholangiocarcinoma in the USA and the Impact of Misclassification

It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known. Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC. The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p < 0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors. The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.

Advances in diagnosis, treatment and palliation of cholangiocarcinoma: 1990-2009

Several advances in diagnosis, treatment and palliation of cholangiocarcinoma (CC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. CC is a relatively rare tumor and the main risk factors are: chronic inflammation, genetic predisposition and congenital abnormalities of the biliary tree. While the incidence of intra-hepatic CC is increasing, the incidence of extra-hepatic CC is trending down. The only curative treatment for CC is surgical resection with negative margins. Liver transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation therapy. Magnetic resonance imaging/magnetic resonance cholangiopancreatography, positron emission tomography scan, endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor staging. Adjuvant therapy, palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable CC. For most of these patients biliary stenting provides effective palliation. Photodynamic therapy is an emerging palliative treatment that seems to provide pain relief, improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization, hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.

Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma in the United States: A Population-Based Case-Control Study

Intrahepatic and extrahepatic cholangiocarcinomas are rare and highly malignant cancers of the bile duct. Although the incidence of extrahepatic cholangiocarcinoma (ECC) has remained constant, the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the United States. Because the etiology of both tumors is poorly understood, a population-based case-control study was conducted to examine the association of ECC and ICC with preexisting medical conditions. Medical conditions among 535 ICC patients, 549 ECC patients (diagnosed 1993-1999), and 102,782 cancer-free controls were identified by using the Surveillance, Epidemiology and End Results-Medicare databases. Logistic regression analysis was used to calculate adjusted odds ratios. In addition to established risk factors (choledochal cysts, cholangitis, inflammatory bowel disease), several other conditions were significantly associated with ECC and ICC: biliary cirrhosis (ECC, ICC: P < .001), cholelithiasis (ECC, ICC: P < .001), alcoholic liver disease (ECC, P < .001; ICC, P = .01), nonspecific cirrhosis (ECC, ICC: P < .001), diabetes (ECC, ICC: P < .001), thyrotoxicosis (ECC, P = .006; ICC, P = .04), and chronic pancreatitis (ECC, ICC: P < .001). Conditions only associated with ICC were obesity (ECC, P = .71; ICC, P = .01), chronic nonalcoholic liver disease (ECC, P = .08; ICC, P = .02), HCV infection (ECC, P = .67; ICC, P = .01), and smoking (ECC, P = .07; ICC, P = .04). Several novel associations with ECC and ICC were identified. HCV infection, chronic nonalcoholic liver disease, and obesity, all of which are increasing in incidence, and smoking were associated only with ICC, suggesting that these conditions might explain the divergent incidence trends of the tumors.

Striking trends in the cholangiocarcinoma incidence and mortality in the United States of America 1979–1998

Background and Methods: Cholangiocarcinoma (CCA) arises from both intra and extrahepatic bile ducts and has been considered a rare tumor in the United States. Recently, worldwide rising mortality due to primary liver tumors including intrahepatic cholangiocarcinoma (IHCC) has been reported. We have analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database to determine the age-adjusted incidence of cholangiocarcinoma and data from the U.S. Vital-Statistics database to determine age-adjusted mortality rates. Results: The incidence of I HCC (leD-9 155.1) progressively increased from 0.12 to 0.81 per 100,000 population between 1979 and 1996 (Figure) associated with a rise in mortality from 0.2 to 0.9 during 1979-1998. Increase in mortality was higher in men (0.2 to 1.1) compared with women (0.2 to 0.8). The percent change in mortality was higher in those aged >75 years. In contrast, the incidence of extrahepatic cholangiocarcinoma (EHCC lOB-9 156.1) decreased from 1.1 to 0.7 (Figure) and the mortality reduced from 0.6 to 0.3 associated with a similar reduction in mortality secondary to gall bladder cancer (iCD-9 156.B} from 1.2 to 0.7 per 100,000 population during this period. Conclusions: The incidence and mortality of intrahepatic cholangiocarcinoma in the USA has increased five fold in the last two decades, the rate of rise of which far exceeds that of hepatocellular carcinoma. This is not readily explained by diagnostic transfer from other tumors or improved diagnosis. Opposing trends in intra and extra hepatic cholangiocarcinoma suggest dissimilar pathogenesis.