Incidence Of Intrahepatic Cholangiocarcinoma Research Articles

Self limiting postoperative hyperbilirubinemia after hepatectomy in a patient of Intrahepatic cholangiocarcinoma with Dubin-Johnson syndrome: A case report

Introduction: Dubin Johnson syndrome (DJS) is a benign disease of bilirubin metabolism, which causes only jaundice since birth, but there are no other symptoms or signs. DJS is so rare that its exact incidence in Indian population is not known. Incidence of intrahepatic cholangiocarcinoma (ICC) is around 3.3%. Occurrence of DJS simultaneous with hepatobiliary malignancies has been reported four times previously, predominantly in the Japanese population. There are no reports of such cases from Indian population. Also, in the reported cases the functional reserves of liver were complicated by presence of pre-existing cirrhosis of liver. There is no data suggesting the influence of concomitant DJS in a patient with liver cancers. Case Report: We present a case of 63-year-old (Indian) male who was diagnosed with DJS in early thirties and on routine health checkup was found to have space occupying lesion in liver. It turned out to be Intra hepatic cholangiocarcinoma on further workup. We state our experience in postoperative management, hyperbilirubinemia as well as further management of disease. Conclusion: Although it is not possible to predict the exact dynamics of DJS over ICC or vice versa, the outcomes of hepatectomy in such scenario are benign, self limiting and do not require any specific treatment.

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.

The miRNAome of Opisthorchis viverrini induced intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a potentially important impact on the public health in the resource-poor regions where this cancer is most prevalent. As microRNAs (miRNAs) remain well preserved after formalin fixation, there is much interest in developing them as biomarkers that can be investigated using tumor biopsy samples preserved in formalin fixed paraffin embedded (FFPE) tumor blocks. Recently, we reported the first comprehensive profiling of tissue-based miRNA expression using FFPE from the three most common subtypes of OV-induced ICC tumors: moderately differentiated ICC, papillary ICC, and well-differentiated ICC. We observed that each subtype of OV-induced ICC exhibited a distinct miRNA profile, which suggested the involvement of specific sets of miRNAs in the progression of this cancer. In addition, non-tumor tissue adjacent to ICC tumor tissue on the same FFPE block shared a similar miRNA dysregulation profile with the tumor tissue than with normal (non-tumor) liver tissue (individuals without ICC or OV infection). Herein, we provide a detailed description of the microarray analysis procedures used to derive these findings.

Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma

Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.

Activating Mutations in PTPN3 Promote Cholangiocarcinoma Cell Proliferation and Migration and Are Associated With Tumor Recurrence in Patients

The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3. Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3(L232R) and PTPN3(L384H), which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence.

Hepatitis B virus infection and intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.

The frequency of KRAS and BRAF mutations in intrahepatic cholangiocarcinomas and their correlation with clinical outcome

The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The prognosis of intrahepatic cholangiocarcinoma is poor, and a better understanding of intrahepatic cholangiocarcinoma tumor biology is needed to more accurately predict clinical outcome and to suggest potential targets for more effective therapies. v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF are frequently mutated oncogenes that promote carcinogenesis in a variety of tumor types. In this study, we analyze a large set of intrahepatic cholangiocarcinoma tumors (n = 54) for mutations in these genes and compare the clinical outcomes of wild type versus KRAS and BRAF mutant cases. Of 54 cases, 7.4% were mutant for KRAS, 7.4% were mutant for BRAF, and these were mutually exclusive. These mutant cases were associated with a higher tumor stage at time of resection and a greater likelihood of lymph node involvement. These cases were also associated with a worse long-term overall survival. Therefore, testing for KRAS and BRAF mutations could be a valuable adjunct in improving both prognosis and outcome stratification among patients with intrahepatic cholangiocarcinoma.

Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case–control analysis

PurposesWe conducted a case–control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC).MethodsThe study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant’Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class.ResultsWe matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73–13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83–5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures.ConclusionsOur findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years.

Fn14 is expressed on neoplastic cholangiocytes in intrahepatic cholangiocarcinoma and promotes necrosis after interaction with TWEAK

BackgroundCholangiocarcinoma is the second most common primary hepatic malignancy worldwide. The incidence of intrahepatic cholangiocarcinoma in the UK has steadily increased over the past 40 years. The main treatment is chemotherapy, and 5-year survival after radical surgery is only 25%. The carcinogenic mechanisms involved in cholangiocarcinoma remain elusive. The fibroblast growth factor-inducible 14 (Fn14)/tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) receptor-ligand system has been shown to be of importance in cellular proliferation and tumour angiogenesis in hepatocellular carcinoma. The aim of this study was to demonstrate the expression of Fn14 and TWEAK in cholangiocarcinoma and determine the functional significance of Fn14/TWEAK interaction on neoplastic cholangiocytes. MethodsHuman liver samples were obtained with consent from the Queen Elizabeth Hospital liver transplant programme. Sections were stained for Fn14 with immunohistochemical techniques. Expression of Fn14 on a cholangiocarcinoma cell line (CC-LP-1) stimulated with TNFα, interferon γ and fibroblast growth factor (FGF) basic was established quantitatively with flow cytometry. Stimulated CC-LP-1 were exposed to different concentrations of TWEAK for 24h. Apoptosis, necrosis, autophagy, and reactive oxygen species production at 24 h were determined by flow cytometry using annexin, 7AAD, dansylcadaverine, and dichlorofluorescein assays, respectively. Proliferation was determined with Ki69 nuclear staining. FindingsImmunohistochemistry revealed Fn14 on the intrahepatic malignant small bile ducts in cholangiocarcinoma. Exposure of neoplastic cholangiocytes to TWEAK for 24h induced necrosis and reduced apoptosis in FGF-activated neoplastic cholangiocytes in a dose-dependent manner. InterpretationFn14 is expressed on neoplastic cholangiocytes in intrahepatic cholangiocarcinoma. Activation of the Fn14/TWEAK receptor-ligand system induces necrosis. The role of Fn14/TWEAK in cholangiocarcinoma needs further investigation to ascertain the mechanisms involved and outcome on overall tumour viability. FundingUK Medical Research Council.

Intrahepatic cholangiocarcinoma in a low endemic area: rising incidence and improved survival

BackgroundTo explore trends in the incidence and survival of patients with intrahepatic cholangiocarcinoma (ICC) an unselected population in Western Europe was studied. MethodsBetween 1989 and 2009, all patients newly diagnosed with ICC were selected from the Netherlands Cancer Registry (n= 809). Trends in incidence, treatment and relative survival were calculated according to gender and age. Follow‐up for vital status was complete until 1st January 2010. ResultsThe incidence rates of ICC increased significantly between 1999 and 2009, especially in the age group 45–59 years [estimated annual percentage change +3.0%, 95% confidence interval (CI) 0.2–5.8]. In the other age groups ICC incidence remained stable. Patients diagnosed with Tumour Lymph Node Metastasis (TNM) stage I mainly underwent surgery (68%), and the majority of the patients with stage II, III and IV received best supportive care (73%). One‐year relative survival for patients with ICC increased significantly from 24% in 1989–1994 to 28% in 2005–2009 (P= 0.03), and corresponding 3‐year relative survival improved from 4% to 8% (P= 0.02). Three‐month and 1‐year relative survival for patients with ICC receiving surgery was 91% and 71%, respectively. DiscussionBetween 1999 and 2009, the incidence of ICC rose, especially in the age group 45–59 years, suggesting aetiological influences. Survival rates have improved during the study period.

125IN - Hepatocellular Carcinoma in the EU

ABSTRACT The incidence of liver cancer varies across Europe. However, while figures have stabilised in Italy and Spain, Northern countries present a slight increase in recent years. In most cases, liver cancer appears in the background of chronic liver disease related to hepatitis C or B, infection and alcoholism, among other risk factors. Current data show that hepatocellular carcinoma is the leading cause of death in patients with cirrhosis and that the incidence of intrahepatic cholangiocarcinoma is on the rise. Because of its clinical relevance all scientific associations have developed practice guidelines to inform patients, physicians and regulatory agents about the established diagnostic and therapeutic procedures. Non-invassive diagnostic criteria have been accepted and in almost all documents the recommended strategy for staging and treatment indication is the BCLC model. Following it, patients diagnosed with HCC are stratified into stages for which different treatment options are to be considered. Disclosure The author has declared no conflicts of interest.

Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis

BackgroundStudies investigating the association between Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and intrahepatic cholangiocarcinoma (ICC) have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship.MethodsA comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated with random-effects models using Review Manager version 5.0.ResultsThirteen case–control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively). For case–control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11) and 3.63 (95% CI, 1.86-7.05), respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44) and 2.60 (95% CI, 1.36-4.97), respectively.ConclusionsThis study suggests that both HBV and HCV infection are associated with an increased risk of ICC.

Biliary Tract Cancers in Olmsted County, Minnesota, 1976–2008

The epidemiology of biliary tract cancers has changed in the United States in the past several decades. The aim of this study is to evaluate biliary tract cancers with regard to the incidence rates, etiology, treatment, and survival in Olmsted County between 1976 and 2008. Community residents over 20 years of age with a newly diagnosed biliary tract cancers were identified using the Rochester Epidemiology Project. Clinical information, including tumor stage, treatment, and survival status was abstracted from the medical records. The incidence rate was calculated considering the entire population of Olmsted County to be at risk and adjusted by age and sex according to US Census 2000 population. Temporal trends of patient survival with biliary tract cancers were assessed. A total of 116 subjects met the study criteria. The age-sex-adjusted incidence rate of intrahepatic cholangiocarcinoma (ICC) increased from 0.3 to 2.1 (P=0.02) but one of gall bladder (GB) cancer decreased from 4.0 to 2.2 (P=0.04) per 100,000 person-years between 1976 and 2008 (P<0.01). Overall incidence rates of remaining biliary tract cancers have not changed. Overall 59% of patients presented with stage 3 or 4 cancers and a median survival was 6.3 months. Survival in patients with biliary tract cancer has minimally improved from median survival of 4.2-7.7 months between 1976 and 2008 (P=0.05). In Olmsted County, the incidence of ICC and GB cancer has increased and decreased, respectively. The prognosis remains poor in community residents diagnosed with biliary tract cancers.

Development of intrahepatic cholangiocarcinoma after a 14‐year follow‐up of a patient with primary sclerosing cholangitis and ulcerative colitis

Intrahepatic cholangiocarcinoma (ICC) is one of the life-threatening complications of primary sclerosing cholangitis (PSC). However, the incidence of ICC in Japanese PSC patients is low, and the association between the development of ICC and morbidity duration of PSC is largely unknown. Here, we describe a case of ICC that developed after a long-term follow-up of a patient with PSC and ulcerative colitis (UC). At the age of 10 years, the patient was first diagnosed with UC and its remission was achieved with systemic steroid therapy. Since then, he was routinely followed-up. At the age of 19 years, laboratory tests showed abnormalities in liver function parameters, and the patient was diagnosed with PSC. Although treatment with ursodeoxycholic acid improved the abnormalities in serum levels of biliary enzymes and no PSC-related symptoms were seen for 13 years, calculous cholecystitis frequently occurred in the patient since the age of 32 years. He developed ICC, which expressed some hepatic progenitor cell markers such as CD133, neural cell adhesion molecule, keratin 7, and keratin 19 at the age of 33 years. ICC was treated by curative partial hepatectomy and adjuvant chemotherapy with gemcitabine. Eight months later, however, the patient developed multiple metastases in the abdominal lymph nodes and lungs, and died 21 months after the onset of ICC. Here, we report a case of ICC that developed after a 14-year follow-up of a patient with PSC and UC.

Abstract 945: Metabolic syndrome increases the risk of primary liver cancer in the United States

Abstract Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two most common histologic types of primary liver cancer. Incidence rates of both HCC and ICC are increasing in the United States. Metabolic syndrome, characterized by increased fasting glucose level, central adiposity, dyslipoproteinemia and hypertension, has been linked with HCC and may also modify the risk of ICC. The magnitude of the association, however, has not been investigated at the population level in the US. We therefore examined the association between metabolic syndrome and the development of both primary liver cancers in the general U.S. population. Methods: All persons aged 65 years and older diagnosed with histologically confirmed HCC and ICC between 1993 and 2005 were identified in the SEER-Medicare linked database. The cases were compared to a 5% sample of individuals residing in the same geographic regions of the SEER registries as the cases. The prevalences of metabolic syndrome and other risk factors for HCC (HBV, HCV, unspecified viral hepatitis, alcoholic liver disease, unspecified cirrhosis, biliary cirrhosis, hemochromatosis, Wilson's disease, smoking) and ICC (biliary cirrhosis, cholangitis, cholelithiasis, choledochal cysts, HBV, HCV, unspecified viral hepatitis, alcoholic liver disease, non-specified cirrhosis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, smoking) were compared among the persons who developed cancer and the persons who did not. Adjusted odds ratios and 95% confidence intervals were calculated using logistic regression. Results: A total of 3,649 HCC cases, 743 ICC cases and 195,953 persons without cancer met the study inclusion criteria. Metabolic syndrome was significantly more common among persons who developed HCC (37.1%) and ICC (29.7%) than among persons who did not (17.1%, p&amp;lt;0.0001). In multiple logistic regression analyses that adjusted for demographics features and the other risk factors, metabolic syndrome remained significantly associated with an increased risk for HCC (OR=2.13; 95%CI=1.96-2.31, p&amp;lt;0.0001) and ICC (OR=1.56; 95% CI = 1.32-1.83, p&amp;lt;0.0001). Conclusions: Metabolic syndrome is a risk factor for development of both HCC and ICC in the general U.S. population. Given that approximately one-third of U.S. adults have metabolic syndrome, these findings have implications for the future incidence of both HCC and ICC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 945. doi:10.1158/1538-7445.AM2011-945

Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

The crude incidence of gallbladder and extrahepatic biliary cancer (ICD-10: C23–C24) in the European Union is ∼3.2 and ∼5.4/100 000 per year for males and females, respectively. Age-adjusted mortality is 1.4 and 1.9/100 000 for males and females, respectively. The incidence of intrahepatic cholangiocarcinoma (ICD-10: C22.1) is increasing and may be estimated as ∼0.9–1.3 and 0.4–0.7/100 000 for males and females, respectively, as 10%–15% of primary liver cancer (ICD-10: C22). In high-risk areas in Europe (south Italy) incidence is estimated at up to ∼4.9–7.4 and ∼2.9–4.3/100 000 for males and females, respectively, and worldwide, e.g.

Cholangiocarcinoma: Descriptive epidemiology and risk factors

In theory, the term of cholangiocarcinoma is reserved for the tumours originating from the intrahepatic bile ducts. The problems of classification of the most frequent hilar tumours and the absence of histopathological confirmation in a large percentage of cases in cancer registries from many countries show the difficulty of establishing the specific epidemiologic behaviour of intrahepatic cholangiocarcinoma (ICC). There are clearly two types of ICC: the first one is the consequence of the recurrent infection of the biliary ducts by the parasites Opisthorchis viverrini and Clonorchis sinensis, and is only seen in the areas of Southeast Asia where liver flukes are endemic. In these areas, incidence and mortality rates of ICC are extremely high. Both parasites have been classified class I carcinogens by the International Agency for Research on Cancer. The other type of ICC is a cancer much rarer but present in the whole world. Some risk factors have been well-established (chronic inflammation of biliary ducts, hepatitis, thorotrast, etc) but many patients do not have any of these factors. An increase in incidence and mortality of this second type of ICC has been seen in recent years, mostly in developed countries. There is an ongoing discussion in the literature about its authenticity and potential causes.

Biliary cancer: ESMO Clinical Recommendation for diagnosis, treatment and follow-up

Biliary cancer: ESMO Clinical Recommendation for diagnosis, treatment and follow-up

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.