Materiały źródłowe

• #1 Cholangiocarcinoma (bile duct cancer) | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/cholangiocarcinoma-bile-duct-cancer?content_id=CON-20167626

  Cholangiocarcinoma happens when cells in the bile ducts develop changes in their DNA. A cell’s DNA contains the instructions that tell a cell what to do. The changes tell the cells to multiply out of control and form a mass of cells (tumor) that can invade and destroy healthy body tissue. It’s not clear what causes the changes that lead to cholangiocarcinoma. […] Factors that may increase your risk of cholangiocarcinoma include: […] Primary sclerosing cholangitis. This disease causes hardening and scarring of the bile ducts. […] Chronic liver disease. Scarring of the liver caused by a history of chronic liver disease increases the risk of cholangiocarcinoma. […] Bile duct problems present at birth. People born with a choledochal cyst, which causes dilated and irregular bile ducts, have an increased risk of cholangiocarcinoma.

• #1 Cholangiocarcinoma (Bile Duct Cancer) Causes & Risk Factors

  https://www.cancercenter.com/cancer-types/bile-duct-cancer/risk-factors

  Bile duct cancer, or cholangiocarcinoma, occurs when cells in the bile duct become damaged or mutated. These damaged cells begin to grow and divide out of control and form a tumor or tumors. […] The exact cause of bile duct cancer is not known, but research indicates that inflammation may play a role in altering the cells’ DNA, causing cancer to form and grow. […] Some conditions that cause chronic inflammation may increase the risk for developing bile duct cancer. […] Patients with type 1 and type 2 diabetes have a higher-than-normal risk for developing bile duct cancer. […] Certain ethnic groups have an increased risk of bile duct cancer. […] Exposure to certain chemicals have been linked to an increased risk of bile duct cancer. […] Long-term infection with hepatitis B or C virus may increase risk.

• #1 Cholangiocarcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560708/

  Cholangiocarcinoma frequently arises in the absence of genetic predisposition and without a clear etiology. However, certain risk factors that vary with ethnicity and geography predispose to cholangiocarcinoma in some patients. These predisposing risk factors include but are not limited to: […] Infestation with liver flukes such as Clonorchis and Opisthorchiasis is strongly associated with cholangiocarcinoma. These infestations are endemic to Southeast Asian regions; the highest incidence rates are in northeast Thailand. Liver fluke infestation is due to the consumption of undercooked fish, and parasite-induced chronic biliary inflammation is the primary driver of malignant transformation. […] Primary sclerosing cholangitis is a progressive autoimmune cholestatic liver disease. Individuals with primary sclerosing cholangitis have a significantly elevated risk, perhaps as much as 400 times the risk, of developing cholangiocarcinoma compared to the general population, especially with concomitant inflammatory bowel disease.

• #1 Bile duct cancer | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/bile-duct-cancer-cholangiocarcinoma/

  Some people can have fluid-filled sacs (cysts) in their bile duct. […] Up to 20% of people with choledochal cysts that are not removed will develop cancer of the bile duct. […] Biliary stones are rare in western Europe, but are relatively common in parts of Asia, such as Japan and Taiwan. It’s estimated that approximately 10% of people with biliary stones will develop bile duct cancer. […] Liver flukes are a type of parasitic insect known to increase the risk of developing bile duct cancer. […] Exposure to certain chemical toxins is known to increase the risk of developing bile duct cancer. […] The following factors are linked with an increased risk of developing bile duct cancer, but more research is still needed: hepatitis B and hepatitis C, cirrhosis (a scarred liver) as a result of drinking excessive amounts of alcohol, HIV, diabetes, obesity, smoking.

• #1 Cholangiocarcinoma: Symptoms, Causes, Types, Staging & Treatment PACE Hospitals – Best Hospitals in Hitech City, Hyderabad, India | Near Madhapur, Kukatpally, KPHB, Kondapur, Gachibowli, Jubilee Hills, Banjara HillsPACE Hospitals Contact

  https://www.pacehospital.com/cholangiocarcinoma-bile-duct-cancer-symptoms-causes-types-staging-treatment

  Recurrent Biliary Infections: Recurrent biliary infections are a risk factor, especially in individuals infected with liver flukes like Clonorchis sinensis and Opisthorchis viverrini, which are common in Southeast Asia. […] Gallstones and Chronic Cholecystitis: Gallstones and chronic cholecystitis can cause persistent irritation of the bile duct epithelium, potentially leading to malignant transformation. Studies have revealed a link between CCA and choledocholithiasis and cholangitis, with risk estimates ranging from 4–64. Primary biliary stones can cause chronic biliary tract inflammation, which raises the risk of cancer. […] Cholangiocarcinoma is classified based on its anatomical location within the biliary tree. This classification helps determine clinical presentation, treatment options, and prognosis. […] The pathogenesis of cholangiocarcinoma is complex and multifactorial, involving chronic inflammation, genetic predisposition, and environmental factors.

• #1 Cholangiocarcinoma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/cholangiocarcinoma?lang=us

  Cholangiocarcinomas (commonest type of bile duct cancers) are malignant epithelial tumors arising from the biliary tree, excluding the gallbladder or ampulla of Vater. Cholangiocarcinoma is the third most common primary hepatobiliary malignancy after hepatocellular carcinoma (HCC) and gallbladder cancer. They tend to have a poor prognosis and high morbidity. […] A number of risk factors for cholangiocarcinoma have been identified, and bile stasis and chronic inflammation of the biliary epithelium are identified as common features among many of them: Caroli disease / choledochal cysts: lifetime risk of 10-15%; choledocholithiasis: more than cholelithiasis; primary sclerosing cholangitis (PSC): especially in Western countries; recurrent pyogenic cholangitis: especially in Southeast Asia; cirrhosis; toxins: e.g. thorotrast, dioxin, polyvinylchloride, heavy alcohol use; viral infections: e.g. HIV, hepatitis B, hepatitis C, EBV; Inflammatory bowel disease (IBD); fibropolycystic liver disease; liver fluke infestation: Opisthorchis spp. and Clonorchis spp.; hepatolithiasis. […] Regarding inflammatory bowel disease, cholangiocarcinoma develops in one in every 100 to 200 patients, which means they have a 4 times greater risk than IBD-free patients. Individuals with ulcerative colitis are at higher risk of having cholangiocarcinoma in comparison to those with Crohn disease.

• #1 Bile Duct Cancer Risk Factors | Cholangiocarcinoma Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/risk-factors.html

  Cirrhosis can be caused by irritants like alcohol and diseases like hepatitis or non-alcoholic fatty liver disease. […] Infection with hepatitis B virus or hepatitis C virus appears to be associated with increased risk for bile duct cancers. […] People with these diseases have an increased risk of bile duct cancer. […] Lynch syndrome, BAP1 tumor predisposition syndrome, cystic fibrosis, and multiple biliary papillomatosis are genetic disorders associated with an increased risk of bile duct cancer. […] Older people are more likely than younger people to get bile duct cancer. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts. […] A radioactive substance called Thorotrast (thorium dioxide) was found to increase the risk for bile duct cancer, as well as other types of liver cancer. […] People with diabetes (type 1 or type 2) have been found to have a higher risk of bile duct cancer. […] People who drink alcohol are more likely to get intrahepatic bile duct cancer. […] Studies have found other factors may also increase the risk of bile duct cancer.

• #1 Cholangiocarcinoma (bile duct cancer) | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/cholangiocarcinoma-bile-duct-cancer?content_id=CON-20167626

  A liver parasite. In areas of Southeast Asia, cholangiocarcinoma is associated with liver fluke infection, which can occur from eating raw or undercooked fish. […] Older age. Cholangiocarcinoma occurs most often in adults over age 50. […] Smoking. Smoking is associated with an increased risk of cholangiocarcinoma. […] Diabetes. People who have type 1 or 2 diabetes may have an increased risk of cholangiocarcinoma. […] Certain inherited conditions. Some DNA changes passed from parents to children cause conditions that increase the risk of cholangiocarcinoma. Examples of these conditions include cystic fibrosis and Lynch syndrome.

• #1 Cholangiocarcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560708/

  Hepatolithiasis, cholelithiasis, and choledocholithiasis increase the risk of developing cholangiocarcinoma, especially with larger stones and a more prolonged illness duration. Hepatolithiasis is more common in Asia and may be associated with parasitic infections. […] Patients with choledochal cysts, biliary mucinous cystic neoplasms, or intraductal papillary biliary mucinous neoplasms are at a significantly increased risk of developing cholangiocarcinoma. […] Chronic infection with hepatitis B or C, hemochromatosis, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly nonalcoholic fatty liver disease or NAFLD), and cirrhosis of any etiology are associated with an increased risk of cholangiocarcinoma. […] Type 2 diabetes, obesity, alcohol consumption, and cigarette smoking increase the risk of developing cholangiocarcinoma. Exposure to Thorotrast, a radioactive thorium dioxide contrast media widely used between 1920 and 1950, increases the risk of cholangiocarcinoma development. Exposure to asbestos and propylene dichloride (1,2-Dichoropropane) also confers an increased risk. […] Patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome), BAP1-related tumor predisposition syndrome, multiple biliary papillomatosis, and cystic fibrosis carry an increased risk of cholangiocarcinoma development.

• #1 Bile Duct Cancer (Cholangiocarcinoma) Causes & Risk Factors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/bile-duct-cancer-cholangiocarcinoma/causes-risk-factors

  People who have chronic (long-standing) inflammation of the bile ducts have an increased risk of developing bile duct cancer. […] Other inflammatory conditions can increase the risk of developing bile duct cancer: […] Ulcerative colitis is an inflammation of the large intestine. It is often associated with inflammation of the bile ducts, which is called primary sclerosing cholangitis. […] Although rarely seen in the United States, food- or water-borne parasites that live in the bile ducts are common in Asia and raise the risk of developing bile duct cancer. […] Congenital bile duct cysts are typically diagnosed in childhood. The lining of these sacs often contains precancerous cells that increase the risk of developing cancer later in life. […] This inflammatory disease is a risk factor for cancer of the intrahepatic bile ducts. […] Studies have suggested that intrahepatic bile duct cancer is more common among heavy smokers. […] Bile duct cancer occurs most often in older people. […] Diabetes can slightly raise the risk for intrahepatic bile duct cancer.

• #1 Bile Duct Cancer (Cholangiocarcinoma): Symptoms. Causes, Tests, Treatments

  https://www.webmd.com/cancer/bile-duct-cancer

  Reflux. When digestive juices from your pancreas flow back into your bile ducts, they can’t empty properly. […] Cirrhosis. Alcohol and hepatitis can damage your liver and cause scar tissue, raising the risk of bile duct cancer. […] Other things that can make you more likely to get bile duct cancer include: Inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), Obesity, Diabetes, Viral hepatitis, Drinking a lot of alcohol.

• #1 What Causes Bile Duct Cancer? | Causes of Bile Duct Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/what-causes.html

  We dont know the exact cause of most bile duct cancers, but we do know some of the risk factors that make a person more likely to develop these cancers. […] There seems to be a link between bile duct cancer and things that irritate and inflame the bile ducts, whether its bile duct stones, infection with a parasite, or something else. […] Scientists are starting to understand how inflammation might lead to certain changes in the DNA of cells, making them grow out of control and form cancers. […] Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Changes in many different genes are usually needed for a cell to become cancer. […] There are few known genetically inherited disorders that are associated with higher risk for bile duct cancer. Gene mutations related to bile duct cancers are usually acquired during life rather than inherited. For example, acquired changes in the TP53 tumor suppressor gene are found in most bile duct cancers. Other genes that may play a role in bile duct cancers include KRAS, HER2, and ALK. […] Some of the gene changes that lead to bile duct cancer might be caused by inflammation. But sometimes the cause of these changes is not known. Many gene changes might just be random events that sometimes happen inside a cell, without having an outside cause.

• #1 About bile duct cancer known as cholangiocarcinoma (CCA)

  https://www.pemazyre.com/what-is-cholangiocarcinoma?s;ph;br;onc;dtc;con=

  Learn about cholangiocarcinoma (CCA), including its subtypes, and one of the causes an abnormal gene change called an FGFR2 fusion. […] Cholangiocarcinoma occurs when the cells lining the bile ducts go through abnormal gene changes, which make the cells grow and divide without stopping. These cancer cells form tumors. […] There are different types of gene changes or defects that can lead to CCA, such as gene mutations, gene amplifications, or gene fusions. […] One specific type of gene fusion that can cause CCA is called a fibroblast growth factor receptor 2 (FGFR2) fusion. […] An FGFR2 fusion is one of the most common types of abnormal gene changes in people with iCCA.

• #1 Cholangiocarcinoma – Diagnosis & Disease Information

  https://www.cancertherapyadvisor.com/ddi/cholangiocarcinoma/

  Cholangiocarcinoma, commonly known as bile duct cancer, is a rare but aggressive malignancy originating in the bile ducts. […] The etiology of cholangiocarcinoma involves a complex interplay of genetic, environmental, and inflammatory factors. Chronic biliary inflammation is a significant risk factor. This often is the result of conditions such as primary sclerosing cholangitis, which is a chronic liver disease, and hepatolithiasis (bile duct stones). […] Parasitic infections, particularly with liver flukes like Opisthorchis viverrini and Clonorchis sinensis, are also strongly associated with cholangiocarcinoma, especially in regions such as Southeast Asia. […] Genetic mutations and alterations play a crucial role in the development of this cancer. Patients who develop cholangiocarcinoma often have mutations in genes such as isocitrate dehydrogenase 1 (IDH1), IDH2, and fibroblast growth factor receptor 2 (FGFR2).

• #1 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. […] Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. […] It is proposed that many of these risk factors cause chronic inflammation and cholestasis, resulting in a cycle of reactive cell proliferation, genetic and epigenetic mutations and eventual cholangiocarcinogenesis.

• #1 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  It is proposed that cholestasis leads to overexposure of cholangiocytes to bile acids that cause abnormal cell proliferation and cholangiocarcinogenesis. […] The increased risk is likely to be due to chronic inflammation secondary to impaired biliary drainage, leading to overexposure of cholangiocytes to bile acids and deconjugated carcinogens that were previously conjugated in the liver, reflux of pancreatic secretions into the bile duct, and bacterial contamination. […] Chronic infection with Hepatitis B and C viruses account for 57% of cases of cirrhosis globally. […] Several meta-analyses show an increased risk of ICC in both hepatitis B and hepatitis C infection. […] The association with hepatitis C is stronger in regions where hepatitis C is endemic, and likewise for hepatitis B.

• #1 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  The evolution from PSC to cholangiocarcinoma might result from DNA damage by biliary inflammation and bile acids in IBD patients with altered DNA repair functions. […] Chronic typhoid carriers carry a six-fold increase for cholangiocarcinoma. […] Chronic infection and sustained inflammation directly or indirectly affecting the biliary tree, leading to mutagenesis, cell proliferation and cancer development. […] Several inflammatory conditions have been linked to the development of cholangiocarcinoma. […] The mechanisms underlying this may be related to common pathways of chronic inflammation and/or gut microbiome dysbiosis. […] Chronic liver injury leads to cirrhosis, which is associated with an increased risk of intrahepatic cholangiocarcinoma. […] The causes of cirrhosis are numerous and include alcohol-associated cirrhosis, non-alcoholic steatohepatitis (NASH), viral hepatitis and autoimmune hepatitis as well as a number of metabolic, congenital and toxic causes.

• #1 Cholangiocarcinoma (Bile Duct Cancer)

  https://my.clevelandclinic.org/health/diseases/21524-cholangiocarcinoma

  Cholangiocarcinoma is a rare cancer that starts in your bile ducts. […] Experts dont know exactly what causes cholangiocarcinoma. But health conditions that cause chronic (long-term) inflammation in your bile ducts may play a role. […] Ongoing damage from inflammation can cause changes in cell DNA. DNA contains the instructions that tell cells how to behave. Damaged DNA can cause problems with how cells grow and divide, creating tumors that damage tissue. These changes probably arent inherited (passed down from biological parents to their children). Instead, they likely happen during a persons lifetime. […] You may be more likely to develop cholangiocarcinoma if you have structural abnormalities where your bile duct and pancreatic duct meet. […] Cholangiocarcinoma is rare. About 8,000 people in the United States develop this cancer each year. […] Worldwide, cholangiocarcinoma is more common in Southeast Asia. Bile duct cancer is a complication of clonorchiasis, a chronic (long-term) infection associated with a Chinese liver fluke parasite.

• #1 Cholangiocarcinoma: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/cholangiocarcinoma/

  Several non-genetic risk factors for cholangiocarcinoma have been identified. These include a bile duct disease called primary sclerosing cholangitis, bile duct stones or cysts, and exposure to certain chemical toxins used in manufacturing. In Southeast Asia, infection with parasitic worms that live in the human bile ducts greatly increase the risk of developing cholangiocarcinoma. Other risk factors that have been studied include long-term infection with viral hepatitis B or C, scarring of the liver (cirrhosis), and chronic diseases such as inflammatory bowel disease and diabetes. Researchers suspect that certain lifestyle factors, including smoking, alcohol use, and obesity, may also contribute to the risk of developing cholangiocarcinoma. […] Studies suggest that a combination of genetic, environmental, and lifestyle factors influence whether a person will develop cholangiocarcinoma. However, most people who develop the disease do not have any of the identified risk factors.

• #1 Cholangiocarcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-021-00300-2

  Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. […] In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. […] In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. […] Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. […] CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.

• #2 Cholangiocarcinoma (Bile Duct Cancer)

  https://my.clevelandclinic.org/health/diseases/21524-cholangiocarcinoma

  Cholangiocarcinoma is a rare cancer that starts in your bile ducts. […] Experts dont know exactly what causes cholangiocarcinoma. But health conditions that cause chronic (long-term) inflammation in your bile ducts may play a role. […] Ongoing damage from inflammation can cause changes in cell DNA. DNA contains the instructions that tell cells how to behave. Damaged DNA can cause problems with how cells grow and divide, creating tumors that damage tissue. These changes probably arent inherited (passed down from biological parents to their children). Instead, they likely happen during a persons lifetime. […] You may be more likely to develop cholangiocarcinoma if you have structural abnormalities where your bile duct and pancreatic duct meet. […] Cholangiocarcinoma is rare. About 8,000 people in the United States develop this cancer each year. […] Worldwide, cholangiocarcinoma is more common in Southeast Asia. Bile duct cancer is a complication of clonorchiasis, a chronic (long-term) infection associated with a Chinese liver fluke parasite.

• #2 Bile duct cancer | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/bile-duct-cancer-cholangiocarcinoma/

  The exact cause of bile duct cancer is unknown. However, some things may increase your chances of developing the condition. The most common include being over 65 years old or having a rare chronic liver disease called primary sclerosing cholangitis (PSC). […] The exact cause of bile duct cancer is unknown, although some things can increase the risk of developing the condition. […] A number of factors that increase the risk of developing bile duct cancer have been identified. […] Your chances of developing cancer of the bile duct increase as you get older. Most people with the condition are over 65 years old. […] Primary sclerosing cholangitis (PSC) is a rare type of liver disease that causes long-lasting (chronic) inflammation of the liver. […] Around 10 to 20% of people with PSC will develop bile duct cancer. Your risk of developing bile duct cancer is thought to be higher if you have PSC and you smoke.

• #2 Bile Duct Cancer Risk Factors | Cholangiocarcinoma Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/risk-factors.html

  Scientists have found a few risk factors that make a person more likely to develop bile duct cancer. […] Certain conditions of the liver or bile ducts have been found to either cause bile duct cancer or to increase the risk of developing it. […] Primary sclerosing cholangitis (PSC) is a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). […] Bile duct stones (hepatolithiasis) are a lot like gallstones, but much smaller. They can also cause inflammation that increases the risk of bile duct cancer. […] Choledochal cyst disease is a rare condition which some people are born with. […] Liver fluke infections can happen when you eat raw or undercooked fish that is infected with these tiny parasitic worms. […] Some people have abnormalities where the bile duct and pancreatic duct normally meet.

• #2 Bile duct cancer | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/bile-duct-cancer-cholangiocarcinoma/

  Some people can have fluid-filled sacs (cysts) in their bile duct. […] Up to 20% of people with choledochal cysts that are not removed will develop cancer of the bile duct. […] Biliary stones are rare in western Europe, but are relatively common in parts of Asia, such as Japan and Taiwan. It’s estimated that approximately 10% of people with biliary stones will develop bile duct cancer. […] Liver flukes are a type of parasitic insect known to increase the risk of developing bile duct cancer. […] Exposure to certain chemical toxins is known to increase the risk of developing bile duct cancer. […] The following factors are linked with an increased risk of developing bile duct cancer, but more research is still needed: hepatitis B and hepatitis C, cirrhosis (a scarred liver) as a result of drinking excessive amounts of alcohol, HIV, diabetes, obesity, smoking.

• #2 Cholangiocarcinoma – Wikipedia

  https://en.wikipedia.org/wiki/Cholangiocarcinoma

  Infection with the bacteria Helicobacter bilis and Helicobacter hepaticus species can cause biliary cancer. […] Congenital liver abnormalities, such as Caroli disease (a specific type of five recognized choledochal cysts), have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma. […] The rare inherited disorders Lynch syndrome II and biliary papillomatosis have also been found to be associated with cholangiocarcinoma. […] Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, has been linked to the development of cholangiocarcinoma as late as 30-40 years after exposure.

• #2 Cholangiocarcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560708/

  Cholangiocarcinoma frequently arises in the absence of genetic predisposition and without a clear etiology. However, certain risk factors that vary with ethnicity and geography predispose to cholangiocarcinoma in some patients. These predisposing risk factors include but are not limited to: […] Infestation with liver flukes such as Clonorchis and Opisthorchiasis is strongly associated with cholangiocarcinoma. These infestations are endemic to Southeast Asian regions; the highest incidence rates are in northeast Thailand. Liver fluke infestation is due to the consumption of undercooked fish, and parasite-induced chronic biliary inflammation is the primary driver of malignant transformation. […] Primary sclerosing cholangitis is a progressive autoimmune cholestatic liver disease. Individuals with primary sclerosing cholangitis have a significantly elevated risk, perhaps as much as 400 times the risk, of developing cholangiocarcinoma compared to the general population, especially with concomitant inflammatory bowel disease.

• #2 Cholangiocarcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560708/

  Hepatolithiasis, cholelithiasis, and choledocholithiasis increase the risk of developing cholangiocarcinoma, especially with larger stones and a more prolonged illness duration. Hepatolithiasis is more common in Asia and may be associated with parasitic infections. […] Patients with choledochal cysts, biliary mucinous cystic neoplasms, or intraductal papillary biliary mucinous neoplasms are at a significantly increased risk of developing cholangiocarcinoma. […] Chronic infection with hepatitis B or C, hemochromatosis, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly nonalcoholic fatty liver disease or NAFLD), and cirrhosis of any etiology are associated with an increased risk of cholangiocarcinoma. […] Type 2 diabetes, obesity, alcohol consumption, and cigarette smoking increase the risk of developing cholangiocarcinoma. Exposure to Thorotrast, a radioactive thorium dioxide contrast media widely used between 1920 and 1950, increases the risk of cholangiocarcinoma development. Exposure to asbestos and propylene dichloride (1,2-Dichoropropane) also confers an increased risk. […] Patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome), BAP1-related tumor predisposition syndrome, multiple biliary papillomatosis, and cystic fibrosis carry an increased risk of cholangiocarcinoma development.

• #2 Bile Duct Cancer Risk Factors | Cholangiocarcinoma Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/risk-factors.html

  Cirrhosis can be caused by irritants like alcohol and diseases like hepatitis or non-alcoholic fatty liver disease. […] Infection with hepatitis B virus or hepatitis C virus appears to be associated with increased risk for bile duct cancers. […] People with these diseases have an increased risk of bile duct cancer. […] Lynch syndrome, BAP1 tumor predisposition syndrome, cystic fibrosis, and multiple biliary papillomatosis are genetic disorders associated with an increased risk of bile duct cancer. […] Older people are more likely than younger people to get bile duct cancer. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts. […] A radioactive substance called Thorotrast (thorium dioxide) was found to increase the risk for bile duct cancer, as well as other types of liver cancer. […] People with diabetes (type 1 or type 2) have been found to have a higher risk of bile duct cancer. […] People who drink alcohol are more likely to get intrahepatic bile duct cancer. […] Studies have found other factors may also increase the risk of bile duct cancer.

• #2

  https://www.parkwayeast.com.sg/conditions-diseases/bile-duct-cancer/symptoms-causes

  Bile duct cancer (cholangiocarcinoma) begins in the cells that line the inside of the bile ducts. […] It is unclear what causes bile duct cancer, but long-term (chronic) inflammation may contribute to its development, as inflammation can damage cells and lead to changes in its DNA, altering the way cells grow. […] These conditions are believed to be risk factors for bile duct cancer: Parasitic infection of the bile duct, Abnormalities where the bile duct and pancreatic duct meet, Choledochal cyst disease, Chronic ulcerative colitis, Cirrhosis of the liver or chronic liver disease, Diabetes, Inflammatory bowel disease, Primary sclerosing cholangitis, Hepatitis B or C, Human immunodeficiency virus (HIV), Non-alcoholic fatty liver disease, Obesity. […] Other factors which may play a role include: Alcohol consumption, which can lead to liver cirrhosis, Exposure to certain toxins, Age, with most cases occurring over the age of 50.

• #2 Cholangiocarcinoma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/cholangiocarcinoma?lang=us

  Cholangiocarcinomas (commonest type of bile duct cancers) are malignant epithelial tumors arising from the biliary tree, excluding the gallbladder or ampulla of Vater. Cholangiocarcinoma is the third most common primary hepatobiliary malignancy after hepatocellular carcinoma (HCC) and gallbladder cancer. They tend to have a poor prognosis and high morbidity. […] A number of risk factors for cholangiocarcinoma have been identified, and bile stasis and chronic inflammation of the biliary epithelium are identified as common features among many of them: Caroli disease / choledochal cysts: lifetime risk of 10-15%; choledocholithiasis: more than cholelithiasis; primary sclerosing cholangitis (PSC): especially in Western countries; recurrent pyogenic cholangitis: especially in Southeast Asia; cirrhosis; toxins: e.g. thorotrast, dioxin, polyvinylchloride, heavy alcohol use; viral infections: e.g. HIV, hepatitis B, hepatitis C, EBV; Inflammatory bowel disease (IBD); fibropolycystic liver disease; liver fluke infestation: Opisthorchis spp. and Clonorchis spp.; hepatolithiasis. […] Regarding inflammatory bowel disease, cholangiocarcinoma develops in one in every 100 to 200 patients, which means they have a 4 times greater risk than IBD-free patients. Individuals with ulcerative colitis are at higher risk of having cholangiocarcinoma in comparison to those with Crohn disease.

• #2 Bile Duct Cancer (Cholangiocarcinoma) | Symptoms & Treatment | MedStar Health

  https://www.medstarhealth.org/services/bile-duct-cancer-cholangiocarcinoma

  Certain liver conditions may increase your risk of bile duct cancer. […] Several factors may increase your risk of developing this type of cancer, including a history of: Chronic bile duct inflammation, Primary sclerosing cholangitis, which progressively scars the bile ducts, Chronic liver diseases, such as cirrhosis, bile duct stones, cholangitis, and polycystic liver disease, Bile duct cysts, Inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis. […] Other risk factors may include age (over 50), obesity, smoking, and excessive alcohol consumption.

• #2 Bile Duct Cancer (Cholangiocarcinoma) Causes & Risk Factors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/bile-duct-cancer-cholangiocarcinoma/causes-risk-factors

  People who have chronic (long-standing) inflammation of the bile ducts have an increased risk of developing bile duct cancer. […] Other inflammatory conditions can increase the risk of developing bile duct cancer: […] Ulcerative colitis is an inflammation of the large intestine. It is often associated with inflammation of the bile ducts, which is called primary sclerosing cholangitis. […] Although rarely seen in the United States, food- or water-borne parasites that live in the bile ducts are common in Asia and raise the risk of developing bile duct cancer. […] Congenital bile duct cysts are typically diagnosed in childhood. The lining of these sacs often contains precancerous cells that increase the risk of developing cancer later in life. […] This inflammatory disease is a risk factor for cancer of the intrahepatic bile ducts. […] Studies have suggested that intrahepatic bile duct cancer is more common among heavy smokers. […] Bile duct cancer occurs most often in older people. […] Diabetes can slightly raise the risk for intrahepatic bile duct cancer.

• #2 Cholangiocarcinoma (Bile Duct Cancer) Causes & Risk Factors

  https://www.cancercenter.com/cancer-types/bile-duct-cancer/risk-factors

  Some diseases of the liver or bile duct, such as polycystic liver disease, pancreatitis, irritable bowel syndrome, choledochal cysts and Carolis syndrome, may increase a persons bile duct cancer risks. […] Being obese may increase the risk for developing some cancers, including bile duct and liver cancer. […] A water-borne parasite called liver fluke may infect the bile duct and cause cancer. […] Tobacco use may increase the risk for developing bile duct cancer.

• #2 Causes and risk factors of bile duct cancer | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/bile-duct-cancer/causes

  The causes of most bile duct cancers are unknown. But there are some factors that can increase your risk of developing it. […] Bile duct cancer is rare. It is not usually clear what has caused bile duct cancer, but there are certain things that can increase the risk of developing it. These are called risk factors. Having a risk factor does not mean you will get cancer. And not having a risk factor does not mean that you will not get it. […] Long-term inflammation or irritation of the bile ducts can increase the risk of bile duct cancer developing. […] In South East Asia, most bile duct cancers are caused by a parasite called the liver fluke. The flukes get into the bile ducts after someone eats foods such as undercooked fish, which is infected with them. […] Cirrhosis can increase your risk of bile duct cancer. Common causes of liver scarring include regularly drinking a lot of alcohol, or infection with the hepatitis B or hepatitis C virus. […] Some faulty genes that are passed on in families (inherited) can cause conditions which increase the risk of bile duct cancer.

• #2 Risks and causes of bile duct cancer | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/risks-causes

  In most cases we don’t know what causes bile duct cancer, but there are some things that can increase the risk. These include being older or having medical conditions that cause long term (chronic) inflammation of the bile ducts. […] The risk of getting bile duct cancer increases as people get older. It can develop at any age but most people are aged 65 and over. […] Primary sclerosing cholangitis (PSC) is a rare type of inflammation of the bile ducts. Doctors don’t know what causes it. People with PSC may have an increased risk of developing cancer of the bile ducts. […] Liver flukes are worms that get into the bile ducts. Having them increases the risk of bile duct cancer. […] People with choledochal cysts have them from birth. […] Doctors usually remove choledochal cysts to reduce the risk of developing bile duct cancer. […] Liver cirrhosis can increase the risk of bile duct cancer. Especially intrahepatic bile duct cancer. […] Some IBDs like ulcerative colitis, can increase the risk of bile duct cancer. […] People who have had Thorotrast in the past have a higher chance of developing bile duct cancer.

• #2 Cholangiocarcinoma: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/277393-overview

  Cholangiocarcinomas arise from the intrahepatic or extrahepatic biliary epithelium. More than 90% are adenocarcinomas, and the remainder are squamous cell tumors. The etiology of most bile duct cancers remains undetermined. Long-standing inflammation, as with primary sclerosing cholangitis (PSC) or chronic parasitic infection, has been suggested to play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation. Intrahepatic cholangiocarcinoma may be associated with chronic ulcerative colitis and chronic cholecystitis. […] Occupational cholangiocarcinoma has been documented in workers at printing companies in Japan who had been exposed to high concentrations of chemical compounds, including 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. […] Heavy infestation by the liver flukes Clonorchis sinensis (endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and far eastern Russia) and Opisthorchis viverrini (the Southeast Asian liver fluke) has been linked to the development of cholangiocarcinoma.

• #2 What is bile duct cancer? Liver and other types

  https://www.medicalnewstoday.com/articles/liver-bile-duct-cancer

  Bile duct cancer, also known as cholangiocarcinoma (CCA), is cancer that affects the bile ducts. […] Although the exact cause of bile duct cancer is unknown, researchers believe that there is a link between bile duct cancer and factors that irritate and inflame the bile ducts. These factors may include bile duct stones, parasite infestation, and bile duct cysts. […] Inflammation in the bile ducts may lead to DNA changes in bile duct cells, which may cause the uncontrolled growth of these cells. […] Gene mutations may also increase the likelihood of bile duct cancer occurring. Some genes that may play a role in bile duct cancers include TP53, KRAS, HER2, and ALK. […] Certain factors can increase the risk of a person developing bile duct cancer. Some risk factors include primary sclerosing cholangitis, chronic ulcerative colitis, Chinese liver fluke parasite infection, bile duct stones, cirrhosis, infection with the hepatitis B or hepatitis C virus, older age, having a high body mass index (BMI), a family history of bile duct cancer, diabetes, and excessive alcohol consumption.

• #2 About bile duct cancer known as cholangiocarcinoma (CCA)

  https://www.pemazyre.com/about-cholangiocarcinoma

  Learn about cholangiocarcinoma (CCA), including its subtypes, and one of the causes an abnormal gene change called an FGFR2 fusion. […] Cholangiocarcinoma occurs when the cells lining the bile ducts go through abnormal gene changes, which make the cells grow and divide without stopping. These cancer cells form tumors. […] There are different types of gene changes or defects that can lead to CCA, such as gene mutations, gene amplifications, or gene fusions. […] Gene fusions occur when parts of two different genes abnormally join together. […] One specific type of gene fusion that can cause CCA is called a fibroblast growth factor receptor 2 (FGFR2) fusion. […] An FGFR2 fusion is one of the most common types of abnormal gene changes in people with iCCA.

• #2 Cholangiocarcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-021-00300-2

  Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. […] In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. […] In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. […] Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. […] CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.

• #2 What Causes Bile Duct Cancer? | Causes of Bile Duct Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/what-causes.html

  We dont know the exact cause of most bile duct cancers, but we do know some of the risk factors that make a person more likely to develop these cancers. […] There seems to be a link between bile duct cancer and things that irritate and inflame the bile ducts, whether its bile duct stones, infection with a parasite, or something else. […] Scientists are starting to understand how inflammation might lead to certain changes in the DNA of cells, making them grow out of control and form cancers. […] Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Changes in many different genes are usually needed for a cell to become cancer. […] There are few known genetically inherited disorders that are associated with higher risk for bile duct cancer. Gene mutations related to bile duct cancers are usually acquired during life rather than inherited. For example, acquired changes in the TP53 tumor suppressor gene are found in most bile duct cancers. Other genes that may play a role in bile duct cancers include KRAS, HER2, and ALK. […] Some of the gene changes that lead to bile duct cancer might be caused by inflammation. But sometimes the cause of these changes is not known. Many gene changes might just be random events that sometimes happen inside a cell, without having an outside cause.

• #2

  https://winshipcancer.emory.edu/cancer-types-and-treatments/bile-duct-cancer/prevention.php

  While scientists have yet to pinpoint exactly what causes bile duct cancer, they have been able to identify certain bile duct cancer risk factors. The following risk factors can affect your chances of developing intrahepatic and extrahepatic cholangiocarcinoma. […] Additionally, having a history of the following liver conditions can raise your risk of developing intrahepatic cholangiocarcinoma: […] While theres no reliable way to prevent cholangiocarcinoma, the following bile duct cancer prevention recommendations may help you reduce your risk for developing the disease:

• #3 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. […] Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. […] It is proposed that many of these risk factors cause chronic inflammation and cholestasis, resulting in a cycle of reactive cell proliferation, genetic and epigenetic mutations and eventual cholangiocarcinogenesis.

• #3 Risks and causes of bile duct cancer | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/bile-duct-cancer/risks-causes

  In most cases we don’t know what causes bile duct cancer, but there are some things that can increase the risk. These include being older or having medical conditions that cause long term (chronic) inflammation of the bile ducts. […] The risk of getting bile duct cancer increases as people get older. It can develop at any age but most people are aged 65 and over. […] Primary sclerosing cholangitis (PSC) is a rare type of inflammation of the bile ducts. Doctors don’t know what causes it. People with PSC may have an increased risk of developing cancer of the bile ducts. […] Liver flukes are worms that get into the bile ducts. Having them increases the risk of bile duct cancer. […] People with choledochal cysts have them from birth. […] Doctors usually remove choledochal cysts to reduce the risk of developing bile duct cancer. […] Liver cirrhosis can increase the risk of bile duct cancer. Especially intrahepatic bile duct cancer. […] Some IBDs like ulcerative colitis, can increase the risk of bile duct cancer. […] People who have had Thorotrast in the past have a higher chance of developing bile duct cancer.

• #3 Cholangiocarcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560708/

  Hepatolithiasis, cholelithiasis, and choledocholithiasis increase the risk of developing cholangiocarcinoma, especially with larger stones and a more prolonged illness duration. Hepatolithiasis is more common in Asia and may be associated with parasitic infections. […] Patients with choledochal cysts, biliary mucinous cystic neoplasms, or intraductal papillary biliary mucinous neoplasms are at a significantly increased risk of developing cholangiocarcinoma. […] Chronic infection with hepatitis B or C, hemochromatosis, metabolic dysfunction-associated steatotic liver disease (MASLD, formerly nonalcoholic fatty liver disease or NAFLD), and cirrhosis of any etiology are associated with an increased risk of cholangiocarcinoma. […] Type 2 diabetes, obesity, alcohol consumption, and cigarette smoking increase the risk of developing cholangiocarcinoma. Exposure to Thorotrast, a radioactive thorium dioxide contrast media widely used between 1920 and 1950, increases the risk of cholangiocarcinoma development. Exposure to asbestos and propylene dichloride (1,2-Dichoropropane) also confers an increased risk. […] Patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome), BAP1-related tumor predisposition syndrome, multiple biliary papillomatosis, and cystic fibrosis carry an increased risk of cholangiocarcinoma development.

• #3 Bile Duct Cancer Risk Factors | Cholangiocarcinoma Risk Factors | American Cancer Society

  https://www.cancer.org/cancer/types/bile-duct-cancer/causes-risks-prevention/risk-factors.html

  Scientists have found a few risk factors that make a person more likely to develop bile duct cancer. […] Certain conditions of the liver or bile ducts have been found to either cause bile duct cancer or to increase the risk of developing it. […] Primary sclerosing cholangitis (PSC) is a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). […] Bile duct stones (hepatolithiasis) are a lot like gallstones, but much smaller. They can also cause inflammation that increases the risk of bile duct cancer. […] Choledochal cyst disease is a rare condition which some people are born with. […] Liver fluke infections can happen when you eat raw or undercooked fish that is infected with these tiny parasitic worms. […] Some people have abnormalities where the bile duct and pancreatic duct normally meet.

• #3 Bile duct cancer | NHS inform

  https://www.nhsinform.scot/illnesses-and-conditions/cancer/cancer-types-in-adults/bile-duct-cancer-cholangiocarcinoma/

  Some people can have fluid-filled sacs (cysts) in their bile duct. […] Up to 20% of people with choledochal cysts that are not removed will develop cancer of the bile duct. […] Biliary stones are rare in western Europe, but are relatively common in parts of Asia, such as Japan and Taiwan. It’s estimated that approximately 10% of people with biliary stones will develop bile duct cancer. […] Liver flukes are a type of parasitic insect known to increase the risk of developing bile duct cancer. […] Exposure to certain chemical toxins is known to increase the risk of developing bile duct cancer. […] The following factors are linked with an increased risk of developing bile duct cancer, but more research is still needed: hepatitis B and hepatitis C, cirrhosis (a scarred liver) as a result of drinking excessive amounts of alcohol, HIV, diabetes, obesity, smoking.

• #3 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  The evolution from PSC to cholangiocarcinoma might result from DNA damage by biliary inflammation and bile acids in IBD patients with altered DNA repair functions. […] Chronic typhoid carriers carry a six-fold increase for cholangiocarcinoma. […] Chronic infection and sustained inflammation directly or indirectly affecting the biliary tree, leading to mutagenesis, cell proliferation and cancer development. […] Several inflammatory conditions have been linked to the development of cholangiocarcinoma. […] The mechanisms underlying this may be related to common pathways of chronic inflammation and/or gut microbiome dysbiosis. […] Chronic liver injury leads to cirrhosis, which is associated with an increased risk of intrahepatic cholangiocarcinoma. […] The causes of cirrhosis are numerous and include alcohol-associated cirrhosis, non-alcoholic steatohepatitis (NASH), viral hepatitis and autoimmune hepatitis as well as a number of metabolic, congenital and toxic causes.

• #3 Molecular Pathogenesis of Cholangiocarcinoma | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5391-0

  It is proposed that cholestasis leads to overexposure of cholangiocytes to bile acids that cause abnormal cell proliferation and cholangiocarcinogenesis. […] The increased risk is likely to be due to chronic inflammation secondary to impaired biliary drainage, leading to overexposure of cholangiocytes to bile acids and deconjugated carcinogens that were previously conjugated in the liver, reflux of pancreatic secretions into the bile duct, and bacterial contamination. […] Chronic infection with Hepatitis B and C viruses account for 57% of cases of cirrhosis globally. […] Several meta-analyses show an increased risk of ICC in both hepatitis B and hepatitis C infection. […] The association with hepatitis C is stronger in regions where hepatitis C is endemic, and likewise for hepatitis B.

• #3

  https://ammf.org.uk/causes-and-risk-factors/

  Newly discovered likely risk factors include obesity, diabetes and fatty liver disease. […] All these factors are suspected but not definitely proven to cause this disease, and further research is needed. […] However, the majority of people diagnosed in the West with cholangiocarcinoma have none of the risk factors mentioned above, their cholangiocarcinoma develops sporadically (ie, no known cause).

• #3 Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2504381/

  In East Asia, where the disease is common, CCA has been pathogenically associated with liver fluke infestation, particularly the endemic Opisthorcis viverrini. […] Various chemicals have been linked to CCA. The banned carcinogenic contrast agent Thorotrast has been strongly associated with CCA, in some cases many years after exposure. […] Cirrhosis from any cause is associated with an increased risk of CCA. […] Hepatitis B (HBV) and hepatitis C (HCV) are established risk factors for hepatocellular carcinoma and may have a role in cholangiocarcinogenesis.

• #3 Cholangiocarcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-021-00300-2

  Cholangiocarcinoma (CCA) is a highly lethal adenocarcinoma of the hepatobiliary system, which can be classified as intrahepatic, perihilar and distal. […] In endemic regions, liver fluke infection is associated with CCA, owing to the oncogenic effect of the associated chronic biliary tract inflammation. […] In other regions, CCA can be associated with chronic biliary tract inflammation owing to choledocholithiasis, cholelithiasis, or primary sclerosing cholangitis, but most CCAs have no identifiable cause. […] Genetic studies have provided new insights into the pathogenesis of CCA, and two aberrations that drive the pathogenesis of non-fluke-associated intrahepatic CCA, fibroblast growth factor receptor 2 fusions and isocitrate dehydrogenase gain-of-function mutations, can be therapeutically targeted. […] CCA remains a highly lethal disease and further scientific and clinical insights are needed to improve patient outcomes.

• #4 Cholangiocarcinoma: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/277393-overview

  Cholangiocarcinomas arise from the intrahepatic or extrahepatic biliary epithelium. More than 90% are adenocarcinomas, and the remainder are squamous cell tumors. The etiology of most bile duct cancers remains undetermined. Long-standing inflammation, as with primary sclerosing cholangitis (PSC) or chronic parasitic infection, has been suggested to play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation. Intrahepatic cholangiocarcinoma may be associated with chronic ulcerative colitis and chronic cholecystitis. […] Occupational cholangiocarcinoma has been documented in workers at printing companies in Japan who had been exposed to high concentrations of chemical compounds, including 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. […] Heavy infestation by the liver flukes Clonorchis sinensis (endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and far eastern Russia) and Opisthorchis viverrini (the Southeast Asian liver fluke) has been linked to the development of cholangiocarcinoma.

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