Materiały źródłowe

• #1 Hilar cholangiocarcinoma (bile duct cancer): stage, treatment, surgery | Dr. Nikhil Agrawal

  https://www.drnikhilagrawal.com/bile-duct-cancer-cholangiocarcinoma-hilar

  Cholangiocarcinoma is a cancer of the bile duct. In this, the inner lining of the bile duct (the tube that carries bile from the liver to intestine) becomes cancerous. […] Hilar cholangiocarcinoma is a form of bile duct cancer which afflicts this part of the biliary tree. This is also termed perihilar cholangiocarcinoma or Klatskin tumour. […] Hilar cholangiocarcinoma is the most common form of bile duct cancer and represents more than half of all cholangiocarcinomas. […] Risk factors for hilar cholangiocarcinoma are: Old age, Primary sclerosing cholangitis (PSC) – It is an autoimmune disease of the bile duct. In this persistent inflammation causes scarring and blockage of the ducts, Cysts of the bile duct (choledochal cysts and Carolis disease) – The lifetime incidence of cholangiocarcinoma in these patients ranges from 6% to 30%. The average age at malignancy detection is 32 years. The risk of malignancy decreases after excision of the cyst, Infection with liver flukes – Liver flukes are parasites that infest bile ducts and cause liver and bile duct diseases. The species causing disease in humans include Clonorchis, Opisthorchis and Fasciola, Cholelithiasis – In this condition stones form in the gallbladder. It is known to predispose to bile duct cancer, Cirrhosis – It is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases, Viral hepatitis – Hepatitis B and C viruses cause a liver disease called hepatitis, Hepatolithiasis – It is a condition in which stones form in the bile duct within the liver. Cancer has been known to occur in 10% of such patients, Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) – These are diseases of the liver caused by obesity, Smoking and alcohol abuse.

• #2 Klatskin Tumors (Hilar Cholangiocarcinoma)

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

  Hilar cholangiocarcinoma develops when normal cells mutate (change) and become abnormal cells. […] Researchers dont know what causes the mutation. They do know some conditions and activities increase your risk, like medical conditions and genetic mutations that happen after youre born. […] Medical conditions that increase the risk of Klatskin tumors include: Alcohol use disorder, Choledocholithiasis, Chronic pancreatitis, Clonorchiasis (infection with a Chinese liver fluke parasite), Primary sclerosing cholangitis, Viruses, including hepatitis B and hepatitis C.

• #3 Hilar cholangiocarcinoma – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/hilar-cholangiocarcinoma/

  Hilar cholangiocarcinoma may not cause symptoms at first. Symptoms typically appear when the cancer grows and blocks the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #4 Hilar cholangiocarcinoma – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/hilar-cholangiocarcinoma/

  Hilar cholangiocarcinoma may not cause symptoms at first. Symptoms typically appear when the cancer grows and blocks the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #5 Hilar cholangiocarcinoma | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20202299/

  Hilar cholangiocarcinoma is a type of cancer that starts as a growth of cells in the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis. Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #6

  https://link.springer.com/article/10.1007/s11684-010-0130-6

  Hilar cholangiocarcinoma, first described by Klatskin in 1965, is a relatively rare tumor arising from the bile ducts. […] The most common disease associated with cholangiocarcinoma is primary sclerosing cholangitis. […] The development of cholangiocarcinoma is a multistep process associated with several mutations in oncogenes and tumor-suppressor genes. […] Lymph node invasion can be found in 30%50% patients at the time of diagnosis, but blood-born metastases are rare and usually occur at late stages. […] Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. […] Risk factors for cholangiocarcinoma in primary sclerosing cholangitis. […] Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. […] Mechanisms of biliary carcinogenesis and growth.

• #7 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.

• #8 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.

• #9

  https://link.springer.com/article/10.1007/s11684-010-0130-6

  Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. […] Risk factors for cholangiocarcinoma. […] Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. […] Inflammation and tumor progression: a lesson from TNF-alpha-dependent FAK signaling in cholangiocarcinoma. […] Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. […] c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma. […] Enhanced epidermal growth factor receptor activation in human cholangiocarcinoma cells. […] Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma.

• #10

  https://link.springer.com/article/10.1007/s11684-010-0130-6

  Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. […] Risk factors for cholangiocarcinoma. […] Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. […] Inflammation and tumor progression: a lesson from TNF-alpha-dependent FAK signaling in cholangiocarcinoma. […] Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell growth and invasion through EP1 receptor-mediated activation of the epidermal growth factor receptor and Akt. […] c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma. […] Enhanced epidermal growth factor receptor activation in human cholangiocarcinoma cells. […] Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma.

• #11 Hilar cholangiocarcinoma: diagnosis, treatment options, and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3955000/

  Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. […] A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. […] A variety of risk factors have been associated with HC including advanced age, male gender, cirrhosis, inflammatory bowel disease, and chronic pancreatitis. Parasitic liver disease (i.e., biliary ascariasis, liver flukes, and liver schistosomiasis) is an established HC risk factor along with biliary tract stone disease. […] The most well established risk factor for HC is primary sclerosing cholangitis (PSC). The lifetime incidence of cholangiocarcinoma (CC) in PSC patients is 6% to 36% with most patients presenting within 2.5 years of their PSC diagnosis. […] Notably, PSC involves both intra and extra hepatic bile ducts and PSC related CC is an equal risk factor for both ICC and ECC.

• #12 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

  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). The cause of the inflammation is not usually known. Many people with PSC also have inflammation of the large intestine, called ulcerative colitis. […] 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. It causes bile-filled sacs along the bile ducts. If not treated, the bile sitting in these sacs causes inflammation of the duct walls. The cells of the duct wall may undergo pre-cancerous changes. Over time, these changes can progress to bile duct cancer.

• #13 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. […] 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.

• #14 Hilar cholangiocarcinoma: diagnosis, treatment options, and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3955000/

  Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. […] A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. […] A variety of risk factors have been associated with HC including advanced age, male gender, cirrhosis, inflammatory bowel disease, and chronic pancreatitis. Parasitic liver disease (i.e., biliary ascariasis, liver flukes, and liver schistosomiasis) is an established HC risk factor along with biliary tract stone disease. […] The most well established risk factor for HC is primary sclerosing cholangitis (PSC). The lifetime incidence of cholangiocarcinoma (CC) in PSC patients is 6% to 36% with most patients presenting within 2.5 years of their PSC diagnosis. […] Notably, PSC involves both intra and extra hepatic bile ducts and PSC related CC is an equal risk factor for both ICC and ECC.

• #15 Epidemiology and risk factors: intrahepatic cholangiocarcinoma – Gupta – Hepatobiliary Surgery and Nutrition

  https://hbsn.amegroups.org/article/view/13610/html

  Patients with PSC have been reported to have a 5-10% lifetime incidence of cholangiocarcinoma, with half of those being diagnosed within 2 years of the diagnosis of PSC. […] Viral hepatitis has recently been shown to be associated with ICC. […] A review of the Surveillance, Epidemiology, and End Results (SEER)-Medicare database revealed that the presence of the metabolic syndrome was a significant risk factor for development of ICC. […] Tobacco smoking has been shown to be associated with increased risk of several different malignancies, and the same is true for ICC. […] Cirrhosis has long been identified as a significant risk factor in HCC development, and a similar pathogenesis has been suggested for ICC in cirrhotics.

• #16 Hilar Cholangiocarcinoma (Klatskin tumor)

  http://www.scielo.org.co/scielo.php?pid=S0120-99572011000200008&script=sci_arttext&tlng=en

  Hilar cholangiocarcinoma (Klatskin tumor) […] Although different risk factors have been suggested, primary sclerosing cholangitis (PSC) and common bile ductal cysts are amongst the most widely recognized. Nevertheless, for most patients including the one presented in this article, no clear risk factor is ever identified. […] A. Primary sclerosing cholangitis (PSC) is an inflammatory disorder that causes fibrosis and stenosis in both intrahepatic and extrahepatic bile ducts. Forty to fifty percent of these patients present active ulcerative colitis. Close to 30% of CC cases have PSC with or without ulcerative colitis. The annual risk of CC associated with PSC is 0.6% to 1.5%. CC appears at earlier ages among patients with PSC (30 to 50 years old). […] B. Polycystic liver disease. Congenital anomalies of the bile duct (Caroli disease, congenital hepatic fibrosis, common bile ductal cysts) have a 15% risk for the development of CC in adulthood.

• #17 Cholangiocarcinoma | PPT

  https://www.slideshare.net/slideshow/cholangiocarcinoma-49870451/49870451

  Cholangiocarcinoma arises from the epithelial cells of the bile ducts and can be intrahepatic, perihilar, or distal. […] Risk factors include primary sclerosing cholangitis, parasitic infections, cholelithiasis, hepatitis, and toxins. […] Primary sclerosing cholangitis (PSC) 30% cholangiocarcinoma diagnosed in PSC UC Develops at younger age (30-50yrs) in PSC Lifetime risk of cholangiocarcinoma in PSC 10-15%. […] Alcohol consumption to be a risk factor for development of cholangiocarcinoma in PSC. […] Viral hepatitis HCV, HBV, cirrhosis risk factors for intra-hepatic cholangiocarcinoma. […] The high prevalence in Asian descent is attributable to endemic chronic parasitic infestation. […] Risk factors include primary sclerosing cholangitis, fibrocystic liver disease, parasitic infection, cholelithiasis and hepatolithiasis, Lynch syndrome, biliary papillomatosis, viral hepatitis, toxins, diabetes, obesity, and HIV.

• #18 Hilar cholangiocarcinoma: diagnosis, treatment options, and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3955000/

  Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. […] A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. […] A variety of risk factors have been associated with HC including advanced age, male gender, cirrhosis, inflammatory bowel disease, and chronic pancreatitis. Parasitic liver disease (i.e., biliary ascariasis, liver flukes, and liver schistosomiasis) is an established HC risk factor along with biliary tract stone disease. […] The most well established risk factor for HC is primary sclerosing cholangitis (PSC). The lifetime incidence of cholangiocarcinoma (CC) in PSC patients is 6% to 36% with most patients presenting within 2.5 years of their PSC diagnosis. […] Notably, PSC involves both intra and extra hepatic bile ducts and PSC related CC is an equal risk factor for both ICC and ECC.

• #19 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. […] 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.

• #20 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

  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). The cause of the inflammation is not usually known. Many people with PSC also have inflammation of the large intestine, called ulcerative colitis. […] 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. It causes bile-filled sacs along the bile ducts. If not treated, the bile sitting in these sacs causes inflammation of the duct walls. The cells of the duct wall may undergo pre-cancerous changes. Over time, these changes can progress to bile duct cancer.

• #21 Hilar cholangiocarcinoma (bile duct cancer): stage, treatment, surgery | Dr. Nikhil Agrawal

  https://www.drnikhilagrawal.com/bile-duct-cancer-cholangiocarcinoma-hilar

  Cholangiocarcinoma is a cancer of the bile duct. In this, the inner lining of the bile duct (the tube that carries bile from the liver to intestine) becomes cancerous. […] Hilar cholangiocarcinoma is a form of bile duct cancer which afflicts this part of the biliary tree. This is also termed perihilar cholangiocarcinoma or Klatskin tumour. […] Hilar cholangiocarcinoma is the most common form of bile duct cancer and represents more than half of all cholangiocarcinomas. […] Risk factors for hilar cholangiocarcinoma are: Old age, Primary sclerosing cholangitis (PSC) – It is an autoimmune disease of the bile duct. In this persistent inflammation causes scarring and blockage of the ducts, Cysts of the bile duct (choledochal cysts and Carolis disease) – The lifetime incidence of cholangiocarcinoma in these patients ranges from 6% to 30%. The average age at malignancy detection is 32 years. The risk of malignancy decreases after excision of the cyst, Infection with liver flukes – Liver flukes are parasites that infest bile ducts and cause liver and bile duct diseases. The species causing disease in humans include Clonorchis, Opisthorchis and Fasciola, Cholelithiasis – In this condition stones form in the gallbladder. It is known to predispose to bile duct cancer, Cirrhosis – It is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases, Viral hepatitis – Hepatitis B and C viruses cause a liver disease called hepatitis, Hepatolithiasis – It is a condition in which stones form in the bile duct within the liver. Cancer has been known to occur in 10% of such patients, Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) – These are diseases of the liver caused by obesity, Smoking and alcohol abuse.

• #22 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

  Liver fluke infections can happen when you eat raw or undercooked fish that is infected with these tiny parasitic worms. In humans, liver flukes live in the bile ducts and can cause bile duct cancer. […] Some people have abnormalities where the bile duct and pancreatic duct normally meet. This can allow digestive juices from the pancreas to reflux (flow back) into the bile ducts. This backward flow keeps the bile from moving through the bile ducts the way it should. People with these abnormalities are at higher risk of bile duct cancer. […] Cirrhosis is damage to the liver caused by scar tissue. Cirrhosis can be caused by irritants like alcohol and diseases like hepatitis or non-alcoholic fatty liver disease. Studies have found it increases the risk of bile duct cancer. […] Infection with hepatitis B virus or hepatitis C virus appears to be associated with increased risk for bile duct cancers. This may be in part because long-term infections with these viruses can also lead to cirrhosis.

• #23 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

  Liver fluke infections can happen when you eat raw or undercooked fish that is infected with these tiny parasitic worms. In humans, liver flukes live in the bile ducts and can cause bile duct cancer. […] Some people have abnormalities where the bile duct and pancreatic duct normally meet. This can allow digestive juices from the pancreas to reflux (flow back) into the bile ducts. This backward flow keeps the bile from moving through the bile ducts the way it should. People with these abnormalities are at higher risk of bile duct cancer. […] Cirrhosis is damage to the liver caused by scar tissue. Cirrhosis can be caused by irritants like alcohol and diseases like hepatitis or non-alcoholic fatty liver disease. Studies have found it increases the risk of bile duct cancer. […] Infection with hepatitis B virus or hepatitis C virus appears to be associated with increased risk for bile duct cancers. This may be in part because long-term infections with these viruses can also lead to cirrhosis.

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

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

  Several inflammatory conditions have been linked to the development of cholangiocarcinoma. […] Chronic infection with Hepatitis B and C viruses account for 57% of cases of cirrhosis globally. […] Diabetes increases the risk of ICC and ECC. […] A new discovery from two recent meta-analyses is the association between Non-Alcoholic Fatty Liver Disease (NAFLD) and cholangiocarcinoma. […] The insulin resistance seen in NAFLD, diabetes and obesity results in compensatory systemic hyperinsulinaemia and increased Insulin-like Growth Factor-1 (IGF-1) production in the liver. […] A number of congenital abnormalities confer a higher risk for developing cholangiocarcinoma. […] IPNB (previously known as biliary papillomatosis) is a rare disease characterised by the presence of multiple papillary adenomas within the bile ducts. It is associated with hepatolithiasis and liver fluke infection in Asian countries (but not in Western countries) implying both genetic and environmental aetiologies.

• #25 Cholangiocarcinoma (Bile Duct Cancer)

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

  Cholangiocarcinoma is a rare cancer that starts in your bile ducts. […] Experts don’t 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 aren’t inherited (passed down from biological parents to their children). Instead, they likely happen during a person’s 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.

• #26 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. […] 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.

• #27 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.

• #28 Hilar cholangiocarcinoma – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/hilar-cholangiocarcinoma/

  Hilar cholangiocarcinoma may not cause symptoms at first. Symptoms typically appear when the cancer grows and blocks the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

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

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

  Patients with PSC have a 15% lifetime incidence of cholangiocarcinoma (equivalent to a 398-fold increased risk compared to the general population) and up to one third will develop cholangiocarcinoma within a year of being diagnosed with PSC. […] It is proposed that cholestasis leads to overexposure of cholangiocytes to bile acids that cause abnormal cell proliferation and cholangiocarcinogenesis. […] Regardless of aetiology, a number of population-based studies have found cirrhosis to be associated with an increased risk of intrahepatic cholangiocarcinoma. […] Gallstones are associated with an increased risk of both ICC and ECC. […] Liver fluke infections are endemic in China, Thailand, Korea, Vietnam, Laos, and Cambodia. Cholangiocarcinoma is associated with infection with Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus species, which are usually transmitted through the consumption of raw or undercooked freshwater fish.

• #30 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. […] 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.

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

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

  Patients with PSC have a 15% lifetime incidence of cholangiocarcinoma (equivalent to a 398-fold increased risk compared to the general population) and up to one third will develop cholangiocarcinoma within a year of being diagnosed with PSC. […] It is proposed that cholestasis leads to overexposure of cholangiocytes to bile acids that cause abnormal cell proliferation and cholangiocarcinogenesis. […] Regardless of aetiology, a number of population-based studies have found cirrhosis to be associated with an increased risk of intrahepatic cholangiocarcinoma. […] Gallstones are associated with an increased risk of both ICC and ECC. […] Liver fluke infections are endemic in China, Thailand, Korea, Vietnam, Laos, and Cambodia. Cholangiocarcinoma is associated with infection with Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus species, which are usually transmitted through the consumption of raw or undercooked freshwater fish.

• #32 Hilar cholangiocarcinoma (bile duct cancer): stage, treatment, surgery | Dr. Nikhil Agrawal

  https://www.drnikhilagrawal.com/bile-duct-cancer-cholangiocarcinoma-hilar

  Cholangiocarcinoma is a cancer of the bile duct. In this, the inner lining of the bile duct (the tube that carries bile from the liver to intestine) becomes cancerous. […] Hilar cholangiocarcinoma is a form of bile duct cancer which afflicts this part of the biliary tree. This is also termed perihilar cholangiocarcinoma or Klatskin tumour. […] Hilar cholangiocarcinoma is the most common form of bile duct cancer and represents more than half of all cholangiocarcinomas. […] Risk factors for hilar cholangiocarcinoma are: Old age, Primary sclerosing cholangitis (PSC) – It is an autoimmune disease of the bile duct. In this persistent inflammation causes scarring and blockage of the ducts, Cysts of the bile duct (choledochal cysts and Carolis disease) – The lifetime incidence of cholangiocarcinoma in these patients ranges from 6% to 30%. The average age at malignancy detection is 32 years. The risk of malignancy decreases after excision of the cyst, Infection with liver flukes – Liver flukes are parasites that infest bile ducts and cause liver and bile duct diseases. The species causing disease in humans include Clonorchis, Opisthorchis and Fasciola, Cholelithiasis – In this condition stones form in the gallbladder. It is known to predispose to bile duct cancer, Cirrhosis – It is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases, Viral hepatitis – Hepatitis B and C viruses cause a liver disease called hepatitis, Hepatolithiasis – It is a condition in which stones form in the bile duct within the liver. Cancer has been known to occur in 10% of such patients, Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) – These are diseases of the liver caused by obesity, Smoking and alcohol abuse.

• #33 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 has a poor prognosis, with a 5-year survival rate varying by stage and treatment. […] The exact cause is unknown, but risk factors include chronic inflammation of the bile ducts, primary sclerosing cholangitis (PSC), liver fluke infection, chronic viral hepatitis (B and C), cirrhosis, bile duct cysts, and exposure to certain chemicals like Thorotrast. Genetic mutations also contribute to tumor development.

• #34 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 has a poor prognosis, with a 5-year survival rate varying by stage and treatment. […] The exact cause is unknown, but risk factors include chronic inflammation of the bile ducts, primary sclerosing cholangitis (PSC), liver fluke infection, chronic viral hepatitis (B and C), cirrhosis, bile duct cysts, and exposure to certain chemicals like Thorotrast. Genetic mutations also contribute to tumor development.

• #35 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 has a poor prognosis, with a 5-year survival rate varying by stage and treatment. […] The exact cause is unknown, but risk factors include chronic inflammation of the bile ducts, primary sclerosing cholangitis (PSC), liver fluke infection, chronic viral hepatitis (B and C), cirrhosis, bile duct cysts, and exposure to certain chemicals like Thorotrast. Genetic mutations also contribute to tumor development.

• #36 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. […] 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.

• #37 Hilar cholangiocarcinoma | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20202299/

  Hilar cholangiocarcinoma is a type of cancer that starts as a growth of cells in the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis. Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #38 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. […] People with PSC may have an increased risk of developing cancer of the bile ducts. One study based in the Netherlands found that more than 5 in 100 people with PSC (more than 5%) went on to develop bile duct cancer. […] 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.

• #39

  https://journals.lww.com/ajg/fulltext/2014/10002/case_of_hilar_cholangiocarcinoma__klatskin_s.1249.aspx

  Cholangiocarcinoma (CC) is a highly malignant tumor of the bile duct with an increasing prevalence world wide. Its etiology is not well understood and a topic of ongoing research. Recent studies have demonstrated the role of hepatitis C (HCV)-related cirrhosis in the pathogenesis of intrahepatic CC (ICC), especially the peripheral type (P-ICC); its role in causation of perihilar CC (PC) and extrahepatic CC (ECC) is incompletely characterized. […] There is growing evidence suggesting the role of HCV infection in the etio-pathogenesis of ECC, including PC. Our case provides support for this hypothesis. Further studies are necessary to confirm an association between HCV infection and PC.

• #40 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

  Cholangiocarcinoma results from chronic inflammation, bile duct injury, and genetic mutations. Below are some of the risk factors that might increase the likelihood of developing this malignancy. […] Cholangiocarcinoma (CCA) risk factors related to chronic biliary inflammation include primary sclerosing cholangitis, chronic hepatitis B and C infections, recurrent biliary infections, gallstones and chronic cholecystitis. […] Primary Sclerosing Cholangitis (PSC): Primary sclerosing cholangitis is a major risk factor for cholangiocarcinoma. Between 2% to 8% of cases of CCA are found in patients with PSC, and it is the leading cause of death in these patients. The lifetime incidence of CCA among PSC patients ranges from 6 to 36%. […] Chronic Hepatitis B and C Infection: Chronic viral hepatitis is a known risk factor for CCA. Hepatitis B and C contribute to hepatobiliary carcinogenesis, increasing the risk of CCA.

• #41 Hilar cholangiocarcinoma (bile duct cancer): stage, treatment, surgery | Dr. Nikhil Agrawal

  https://www.drnikhilagrawal.com/bile-duct-cancer-cholangiocarcinoma-hilar

  Cholangiocarcinoma is a cancer of the bile duct. In this, the inner lining of the bile duct (the tube that carries bile from the liver to intestine) becomes cancerous. […] Hilar cholangiocarcinoma is a form of bile duct cancer which afflicts this part of the biliary tree. This is also termed perihilar cholangiocarcinoma or Klatskin tumour. […] Hilar cholangiocarcinoma is the most common form of bile duct cancer and represents more than half of all cholangiocarcinomas. […] Risk factors for hilar cholangiocarcinoma are: Old age, Primary sclerosing cholangitis (PSC) – It is an autoimmune disease of the bile duct. In this persistent inflammation causes scarring and blockage of the ducts, Cysts of the bile duct (choledochal cysts and Carolis disease) – The lifetime incidence of cholangiocarcinoma in these patients ranges from 6% to 30%. The average age at malignancy detection is 32 years. The risk of malignancy decreases after excision of the cyst, Infection with liver flukes – Liver flukes are parasites that infest bile ducts and cause liver and bile duct diseases. The species causing disease in humans include Clonorchis, Opisthorchis and Fasciola, Cholelithiasis – In this condition stones form in the gallbladder. It is known to predispose to bile duct cancer, Cirrhosis – It is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases, Viral hepatitis – Hepatitis B and C viruses cause a liver disease called hepatitis, Hepatolithiasis – It is a condition in which stones form in the bile duct within the liver. Cancer has been known to occur in 10% of such patients, Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH) – These are diseases of the liver caused by obesity, Smoking and alcohol abuse.

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

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

  Several inflammatory conditions have been linked to the development of cholangiocarcinoma. […] Chronic infection with Hepatitis B and C viruses account for 57% of cases of cirrhosis globally. […] Diabetes increases the risk of ICC and ECC. […] A new discovery from two recent meta-analyses is the association between Non-Alcoholic Fatty Liver Disease (NAFLD) and cholangiocarcinoma. […] The insulin resistance seen in NAFLD, diabetes and obesity results in compensatory systemic hyperinsulinaemia and increased Insulin-like Growth Factor-1 (IGF-1) production in the liver. […] A number of congenital abnormalities confer a higher risk for developing cholangiocarcinoma. […] IPNB (previously known as biliary papillomatosis) is a rare disease characterised by the presence of multiple papillary adenomas within the bile ducts. It is associated with hepatolithiasis and liver fluke infection in Asian countries (but not in Western countries) implying both genetic and environmental aetiologies.

• #43 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. […] 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.

• #44 Hilar cholangiocarcinoma – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/hilar-cholangiocarcinoma/

  Hilar cholangiocarcinoma may not cause symptoms at first. Symptoms typically appear when the cancer grows and blocks the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #45 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

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

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

  Cholangiocarcinomas correspond to ~15% of all primary liver tumors and to ~3% of all gastrointestinal malignancies. […] 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. […] 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. […] A hilar-perihilar tumor is considered unresectable in the following cases: Bismuth type IV: bilateral secondary biliary radicle involvement, main portal vein encasement/occlusion, atrophy of a liver lobe with contralateral portal vein or hepatic artery encasement, atrophy of a liver lobe with contralateral secondary biliary radicle involvement, involvement of both hepatic arteries.

• #47 Cholangiocarcinoma Clinical Presentation: History, Physical, Causes

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

  The lifetime risk of developing this cancer in the setting of primary sclerosing cholangitis is 10-20%. At increased risk are patients with ulcerative colitis without symptomatic primary sclerosing cholangitis and a small subset of patients with Crohn disease. […] Certain chemical exposures have been implicated in the development of bile duct cancers, primarily in workers in the aircraft, rubber, and wood-finishing industries. […] Cholangiocarcinoma has developed decades after administration of the radiologic contrast medium thorium dioxide (ie, Thorotrast). […] Congenital diseases of the biliary tree, including choledochal cysts and Caroli disease, have been associated with cholangiocarcinoma. […] Other conditions rarely associated with cholangiocarcinoma include bile duct adenomas, biliary papillomatosis, and alpha1-antitrypsin deficiency. Obesity may also be a risk factor.

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

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

  Cholangiocarcinomas correspond to ~15% of all primary liver tumors and to ~3% of all gastrointestinal malignancies. […] 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. […] 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. […] A hilar-perihilar tumor is considered unresectable in the following cases: Bismuth type IV: bilateral secondary biliary radicle involvement, main portal vein encasement/occlusion, atrophy of a liver lobe with contralateral portal vein or hepatic artery encasement, atrophy of a liver lobe with contralateral secondary biliary radicle involvement, involvement of both hepatic arteries.

• #49 Cholangiocarcinoma (bile duct cancer) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cholangiocarcinoma/symptoms-causes/syc-20352408

  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: […] Cholangiocarcinoma occurs most often in adults over age 50. […] Smoking is associated with an increased risk of cholangiocarcinoma. […] 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.

• #50 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

• #51 Hilar Cholangiocarcinoma (Klatskin tumor)

  http://www.scielo.org.co/scielo.php?pid=S0120-99572011000200008&script=sci_arttext&tlng=en

  C. Parasitic disease. In the East, there are recognized biliary parasites (Clonorchis sinensis and Opistorchis viverrini) associated with CC. They induce chronic inflammation which has been related to the malignant transformation of the epithelium. […] D. Colelithiasis and hepatolithiasis. The relation between vesicular calculi and CC is not as B as that between cholethiasis and vesicular cancer. […] E. Exposure to toxins. There is a clear association between exposure to Thorotrast (a radiological contrast agent used during the 60s) and the appearance of cholangiocarcinomas. […] F. Lynch syndrome and biliary papillomatosis. Lynch syndrome, or non-polyposis colorectal cancer, is a dominant autosomal hereditary disorder which has a high risk of leading not only to colon cancer, but also to ovarian, endometrial, brain and skin cancer related to the presence of CC. […] G. Chronic liver disease. The hepatitis B virus (HBV), hepatitis C virus (HCV) and cirrhosis have all been associated with intrahepatic CC. […] H. HIV infection. HIV infections have been associated with a risk of CC up to 6.4 times greater.

• #52 What Is Metastatic Bile Duct Cancer and What Causes It?

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

  Bile duct cancer also called cholangiocarcinoma is a rare condition. […] Researchers dont know exactly what causes cells in your bile ducts to become cancerous. But certain things increase your chances of having bile duct cancer. They include: Primary sclerosing cholangitis, a disease that causes your bile ducts to harden and scar […] Chronic liver disease that scars this organ […] Choledochal cyst, a bile duct problem you may be born with […] Liver fluke infection, a problem caused by a parasite. Its particularly a problem in Southeast Asia and is linked to eating raw or undercooked fish […] Age the condition is most common if you are older than 50 […] Smoking […] Diabetes, type 1 or type 2 […] Inherited conditions, such as cystic fibrosis or Lynch syndrome, a cause of hereditary colon cancer.

• #53 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. […] 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.

• #54 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

• #55 Cholangiocarcinoma (bile duct cancer) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cholangiocarcinoma/symptoms-causes/syc-20352408

  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: […] Cholangiocarcinoma occurs most often in adults over age 50. […] Smoking is associated with an increased risk of cholangiocarcinoma. […] 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.

• #56 Cholangiocarcinoma (bile duct cancer) | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/cholangiocarcinoma-bile-duct-cancer

  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: […] A liver parasite. In areas of Southeast Asia, cholangiocarcinoma is associated with liver fluke infection, which can occur from eating raw or undercooked fish. […] 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.

• #57 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. […] 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.

• #58 Understanding Hilar Cholangiocarcinoma: Causes, Symptoms, Diagnosis, and Treatment

  https://www.doctorshubnepal.com/diseases-conditions/hilar-cholangiocarcinoma

  Hilar cholangiocarcinoma arises from genetic mutations and cellular changes within the bile duct epithelium. Some primary causes include: […] Chronic Inflammation: Conditions such as primary sclerosing cholangitis (PSC) and chronic biliary infections increase the risk. […] Genetic Mutations: Abnormalities in genes like KRAS, TP53, and IDH1/2 contribute to the development of the tumor. […] Parasitic Infections: Liver fluke infections, common in certain regions, are linked to increased cancer risk. […] Primary Biliary Cholangitis: An autoimmune disease leading to bile duct damage and subsequent cancer risk. […] Exposure to Chemicals: Long-term exposure to certain industrial chemicals and substances may increase risk.

• #59 Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist

  https://www.e-jlc.org/journal/view.php?number=549

  iCCA is often associated with biliary diseases, such as primary sclerosing cholangitis (PSC), hepatolithiasis, and parasites (liver fluke). Recently, however, chronic hepatitis due to viral hepatitis, and metabolic syndrome, have also been found to be risk factors for iCCA. […] Interestingly, the etiology has a close relationship with the subtype of iCCA: the large duct type often arises in PSC, hepatolithiasis, and parasitic infection, which all cause chronic inflammation. In contrast, viral hepatitis and metabolic syndrome are more common in the small duct type. […] Approximately 50% of iCCAs have actionable mutations that can be treated with commercially available medications. The most frequently observed alterations are isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations (18.3%) and fibroblast growth factor receptor 2 (FGFR2) fusions (11.6%), followed by ERBB2 (5.1%), and BRAF (5.0%).

• #60 Cholangiocarcinoma – Diagnosis & Disease Information

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

  Additionally, exposure to certain toxins, such as thorotrast (a radiographic contrast agent banned in the 1960s) and nitrosamines, has been linked to an increased risk of developing cholangiocarcinoma. […] Lifestyle factors, including smoking and chronic alcohol consumption, may also contribute to its pathogenesis.

• #61 Cholangiocarcinoma Clinical Presentation: History, Physical, Causes

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

  The lifetime risk of developing this cancer in the setting of primary sclerosing cholangitis is 10-20%. At increased risk are patients with ulcerative colitis without symptomatic primary sclerosing cholangitis and a small subset of patients with Crohn disease. […] Certain chemical exposures have been implicated in the development of bile duct cancers, primarily in workers in the aircraft, rubber, and wood-finishing industries. […] Cholangiocarcinoma has developed decades after administration of the radiologic contrast medium thorium dioxide (ie, Thorotrast). […] Congenital diseases of the biliary tree, including choledochal cysts and Caroli disease, have been associated with cholangiocarcinoma. […] Other conditions rarely associated with cholangiocarcinoma include bile duct adenomas, biliary papillomatosis, and alpha1-antitrypsin deficiency. Obesity may also be a risk factor.

• #62 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. […] 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.

• #63 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

  A radioactive substance called Thorotrast (thorium dioxide) was used as a contrast agent for x-rays until the 1950s, when its production and use was banned. It 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. The risk is higher in those who have liver problems from drinking alcohol. […] Studies have found other factors may also increase the risk of bile duct cancer. But for these factors, the link to bile duct cancer risk is not as clear.

• #64 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. […] 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.

• #65 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.

• #66 Cholangiocarcinoma – Diagnosis & Disease Information

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

  Additionally, exposure to certain toxins, such as thorotrast (a radiographic contrast agent banned in the 1960s) and nitrosamines, has been linked to an increased risk of developing cholangiocarcinoma. […] Lifestyle factors, including smoking and chronic alcohol consumption, may also contribute to its pathogenesis.

• #67 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. […] 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.

• #68 Cholangiocarcinoma: MedlinePlus GeneticsLock

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

  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.

• #69 Cholangiocarcinoma (bile duct cancer) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cholangiocarcinoma/symptoms-causes/syc-20352408

  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: […] Cholangiocarcinoma occurs most often in adults over age 50. […] Smoking is associated with an increased risk of cholangiocarcinoma. […] 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.

• #70 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.

• #71 Klatskin Tumors (Hilar Cholangiocarcinoma)

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

  Hilar cholangiocarcinoma develops when normal cells mutate (change) and become abnormal cells. […] Researchers dont know what causes the mutation. They do know some conditions and activities increase your risk, like medical conditions and genetic mutations that happen after youre born. […] Medical conditions that increase the risk of Klatskin tumors include: Alcohol use disorder, Choledocholithiasis, Chronic pancreatitis, Clonorchiasis (infection with a Chinese liver fluke parasite), Primary sclerosing cholangitis, Viruses, including hepatitis B and hepatitis C.

• #72 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

  A radioactive substance called Thorotrast (thorium dioxide) was used as a contrast agent for x-rays until the 1950s, when its production and use was banned. It 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. The risk is higher in those who have liver problems from drinking alcohol. […] Studies have found other factors may also increase the risk of bile duct cancer. But for these factors, the link to bile duct cancer risk is not as clear.

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

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

  Bile duct cancer (cholangiocarcinoma) is uncommon, accounting for 10 percent to 20 percent of liver cancers. 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. […] 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.

• #74 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

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

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

  Bile duct cancer (cholangiocarcinoma) is uncommon, accounting for 10 percent to 20 percent of liver cancers. 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. […] 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.

• #76 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

  A radioactive substance called Thorotrast (thorium dioxide) was used as a contrast agent for x-rays until the 1950s, when its production and use was banned. It 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. The risk is higher in those who have liver problems from drinking alcohol. […] Studies have found other factors may also increase the risk of bile duct cancer. But for these factors, the link to bile duct cancer risk is not as clear.

• #77 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

• #78 Cholangiocarcinoma- Symptoms, Types, Causes, & More

  https://www.impactguru.com/info/cholangiocarcinoma/

  Cholangiocarcinoma tends to occur more frequently in older individuals, with the risk increasing with age. Additionally, men are more commonly affected than women. […] While rare, some inherited genetic conditions, such as Lynch syndrome and biliary cystic diseases, may predispose individuals to develop cholangiocarcinoma. […] Its important to note that in many cases, the exact cause of cholangiocarcinoma remains unknown. A mixture of genetic, environmental, and lifestyle factors likely contributes to its development.

• #79 Cholangiocarcinoma (bile duct cancer) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cholangiocarcinoma/symptoms-causes/syc-20352408

  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: […] Cholangiocarcinoma occurs most often in adults over age 50. […] Smoking is associated with an increased risk of cholangiocarcinoma. […] 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.

• #80 Hilar cholangiocarcinoma – Hancock Health

  https://www.hancockhealth.org/fr/mayo-health-library/hilar-cholangiocarcinoma/

  Hilar cholangiocarcinoma may not cause symptoms at first. Symptoms typically appear when the cancer grows and blocks the bile ducts. […] Its not clear what causes most hilar cholangiocarcinomas. This cancer starts in the bile ducts that connect the liver to the small intestine. […] Hilar cholangiocarcinoma happens when cells in a bile duct develop changes in their DNA. A cells DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] Factors that may increase the risk of hilar cholangiocarcinoma include: Primary sclerosing cholangitis causes hardening and scarring of the bile ducts that can lead to cancer. Older age. Hilar cholangiocarcinoma happens most often in adults over age 50. Inflammatory bowel disease. People who have ongoing inflammation of the digestive tract have an increased risk of hilar cholangiocarcinoma. Liver cirrhosis causes scarring of the liver that increases the risk of hilar cholangiocarcinoma. Bile duct cysts cause dilated and irregular bile ducts. Having bile duct cysts increases risk of hilar cholangiocarcinoma. Gallbladder conditions. Ongoing inflammation of the gallbladder, called cholecystitis, increases the risk of hilar cholangiocarcinoma. People who develop gallstones also are at an increased risk. Liver parasites. In areas of Southeast Asia, hilar cholangiocarcinoma is linked to liver flukes, which are parasites that can infect humans. Liver fluke infection can happen from eating raw or undercooked fish.

• #81 Hilar cholangiocarcinoma: diagnosis, treatment options, and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3955000/

  Hilar cholangiocarcinoma (HC) is a rare disease with a poor prognosis which typically presents in the 6th decade of life. […] A variety of risk factors have been associated with HC, most notably primary sclerosing cholangitis (PSC), biliary stone disease and parasitic liver disease. […] A variety of risk factors have been associated with HC including advanced age, male gender, cirrhosis, inflammatory bowel disease, and chronic pancreatitis. Parasitic liver disease (i.e., biliary ascariasis, liver flukes, and liver schistosomiasis) is an established HC risk factor along with biliary tract stone disease. […] The most well established risk factor for HC is primary sclerosing cholangitis (PSC). The lifetime incidence of cholangiocarcinoma (CC) in PSC patients is 6% to 36% with most patients presenting within 2.5 years of their PSC diagnosis. […] Notably, PSC involves both intra and extra hepatic bile ducts and PSC related CC is an equal risk factor for both ICC and ECC.

• #82 Bile Duct Cancer Treatment in Delhi, India | Cholangiocarcinoma Symptoms & Causes

  https://www.blkmaxhospital.com/our-specialities/gastrointestinal-cancer/conditions-treatments/bile-duct-cancer

  Hilar Cholangiocarcinoma is a condition that develops in the bile ducts, which are located just outside of the liver. Perihilar cholangiocarcinoma is another name for this type of cancer. […] Hilar Cholangiocarcinoma occurs in the bile duct region nearest to the duodenem. This form of cholangiocarcinoma is also known as Extrahepatic Cholangiocarcinoma. […] Bile Duct Cancer Causes include old age, ethnicity, Type 1 and Type 2 Diabetes may be associated with Cholangiocarcinoma, hepatitis infection, obesity, family history, excessive alcohol consumption, smoking, and exposure to toxic chemicals. […] Some individuals are more prone to developing this cancer. These include the following: people from Asia, as compared to people from the West; men more vulnerable to this disease; obese individuals; individuals aged more than 60 years; tobacco smokers; diabetics; individuals suffering from viral illnesses such as hepatitis B, hepatitis C, and HIV; liver diseases such as cirrhosis, gallbladder cancer, and biliary papillomatosis; patients with chronic bile duct irritation. These disorders produce bile duct inflammation and predispose one to cancer. This would include primary sclerosing cholangitis, liver fluke (worm) infection, bile stones, and bile duct abnormalities such as cysts; individuals who have been exposed to certain chemicals and medications, including asbestos, thorotrast, dioxin, methyldopa, isoniazid, and older oral contraceptives etc.

• #83 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

  Inflammatory bowel disease includes ulcerative colitis and Crohns disease. People with these diseases have an increased risk of bile duct cancer. […] Genetic disorders are gene-related changes that you are born with. 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. Most people diagnosed with bile duct cancer are in their 60s or 70s. […] In the US, the risk of bile duct cancer is highest among Hispanic Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas. […] Having excess body weight or obesity can increase the risk of cancers of the gallbladder and bile ducts.

• #84 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.

• #85 Klatskin Tumors (Hilar Cholangiocarcinoma)

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

  Hilar cholangiocarcinoma develops when normal cells mutate (change) and become abnormal cells. […] Researchers dont know what causes the mutation. They do know some conditions and activities increase your risk, like medical conditions and genetic mutations that happen after youre born. […] Medical conditions that increase the risk of Klatskin tumors include: Alcohol use disorder, Choledocholithiasis, Chronic pancreatitis, Clonorchiasis (infection with a Chinese liver fluke parasite), Primary sclerosing cholangitis, Viruses, including hepatitis B and hepatitis C.

• #86 Klatskin Tumor | OncoLink

  https://www.oncolink.org/cancers/gastrointestinal/cholangiocarcinoma/support-and-resources/klatskin-tumor

  Klatskin tumors are a type of cholangiocarcinoma. Cholangiocarcinoma is cancer of the bile duct system in the liver. It is found at the liver hilum and can also be called hilar cholangiocarcinoma. […] It is not known what causes a Klatskin tumor. There are risk factors that can cause bile duct system inflammation that could be related to Klatskin tumor development. These risk factors include primary sclerosing cholangitis, parasitic infections, ulcerative colitis, viral hepatitis, cirrhosis, bile duct stones, and choledochal cysts. Other possible risk factors include aging, alcohol use, diabetes, obesity, family history, inflammatory bowel disease, smoking, chronic pancreatitis, infection with HIV, and exposure to radioactive chemicals.

• #87 Hilar Cholangiocarcinoma (Klatskin tumor)

  http://www.scielo.org.co/scielo.php?pid=S0120-99572011000200008&script=sci_arttext&tlng=en

  C. Parasitic disease. In the East, there are recognized biliary parasites (Clonorchis sinensis and Opistorchis viverrini) associated with CC. They induce chronic inflammation which has been related to the malignant transformation of the epithelium. […] D. Colelithiasis and hepatolithiasis. The relation between vesicular calculi and CC is not as B as that between cholethiasis and vesicular cancer. […] E. Exposure to toxins. There is a clear association between exposure to Thorotrast (a radiological contrast agent used during the 60s) and the appearance of cholangiocarcinomas. […] F. Lynch syndrome and biliary papillomatosis. Lynch syndrome, or non-polyposis colorectal cancer, is a dominant autosomal hereditary disorder which has a high risk of leading not only to colon cancer, but also to ovarian, endometrial, brain and skin cancer related to the presence of CC. […] G. Chronic liver disease. The hepatitis B virus (HBV), hepatitis C virus (HCV) and cirrhosis have all been associated with intrahepatic CC. […] H. HIV infection. HIV infections have been associated with a risk of CC up to 6.4 times greater.

• #88 Cholangiocarcinoma – Wikipedia

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

  Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), ulcerative colitis, cirrhosis, hepatitis C, hepatitis B, infection with certain liver flukes, and some congenital liver malformations. […] Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes Opisthorchis viverrini (found in Thailand, Laos PDR, and Vietnam) or Clonorchis sinensis (found in China, Taiwan, eastern Russia, Korea, and Vietnam) has been associated with the development of cholangiocarcinoma. […] The gut microbiota and bile acid activity are intricately linked and likely play crucial roles in cholangiocarcinoma development. […] People with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or hepatitis C), alcoholic liver disease, or cirrhosis of the liver due to other causes, are at significantly increased risk of cholangiocarcinoma.

• #89 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.

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

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

  Patients with PSC have a 15% lifetime incidence of cholangiocarcinoma (equivalent to a 398-fold increased risk compared to the general population) and up to one third will develop cholangiocarcinoma within a year of being diagnosed with PSC. […] It is proposed that cholestasis leads to overexposure of cholangiocytes to bile acids that cause abnormal cell proliferation and cholangiocarcinogenesis. […] Regardless of aetiology, a number of population-based studies have found cirrhosis to be associated with an increased risk of intrahepatic cholangiocarcinoma. […] Gallstones are associated with an increased risk of both ICC and ECC. […] Liver fluke infections are endemic in China, Thailand, Korea, Vietnam, Laos, and Cambodia. Cholangiocarcinoma is associated with infection with Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus species, which are usually transmitted through the consumption of raw or undercooked freshwater fish.

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

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

  Many risk factors have been implicated in cholangiocarcinogenesis, but the evidence supporting each factor is often limited to population-based studies with the inherit limitations of such study designs. […] An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies to tackle this disease.

• #92

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

  The exact cause of cholangiocarcinoma is unclear. It is likely that this cancer arises due to a combination of factors, including other illnesses that cause chronic damage to the liver and/or bile ducts, certain toxins and possibly a small genetic predisposition, although it is not a directly inherited disease. […] The following risk factors are all accepted by scientists to increase the likelihood of developing cholangiocarcinoma: Primary sclerosing cholangitis (PSC) PSC, a condition where the bile ducts are chronically inflamed, is the commonest known predisposing cause of cholangiocarcinoma. […] There is some evidence that long term liver damage of any cause, such as chronic viral hepatitis B or C, and alcohol may also be risk factors for cholangiocarcinoma. Newly discovered likely risk factors include obesity, diabetes and fatty liver disease. […] 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).

• #93

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

  The exact cause of cholangiocarcinoma is unclear. It is likely that this cancer arises due to a combination of factors, including other illnesses that cause chronic damage to the liver and/or bile ducts, certain toxins and possibly a small genetic predisposition, although it is not a directly inherited disease. […] The following risk factors are all accepted by scientists to increase the likelihood of developing cholangiocarcinoma: Primary sclerosing cholangitis (PSC) PSC, a condition where the bile ducts are chronically inflamed, is the commonest known predisposing cause of cholangiocarcinoma. […] There is some evidence that long term liver damage of any cause, such as chronic viral hepatitis B or C, and alcohol may also be risk factors for cholangiocarcinoma. Newly discovered likely risk factors include obesity, diabetes and fatty liver disease. […] 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).

• #94

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

  Cholangiocarcinoma is relatively rare in the U.S. Still, its important to learn about bile duct cancer prevention so you can protect yourself. […] While researchers are still working to understand exactly what causes bile duct cancer and have yet to make specific recommendations regarding bile duct cancer prevention, they have identified some risk factors for the disease. […] Its not entirely clear what causes bile duct cancer, although researchers are learning more about the cancer each day. As with other types of cancer, bile duct cancer develops when abnormal cells grow out of control and form a tumor. This is generally caused by changes to cell DNA, called genetic mutations. The genetic mutations that lead to cholangiocarcinoma do not appear to be inheritable, meaning they are not passed down from one generation to the next. The vast majority of patients who develop bile duct cancer have no family history of the disease.

• #95 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.

• #96 Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist

  https://www.e-jlc.org/journal/view.php?number=549

  iCCA is often associated with biliary diseases, such as primary sclerosing cholangitis (PSC), hepatolithiasis, and parasites (liver fluke). Recently, however, chronic hepatitis due to viral hepatitis, and metabolic syndrome, have also been found to be risk factors for iCCA. […] Interestingly, the etiology has a close relationship with the subtype of iCCA: the large duct type often arises in PSC, hepatolithiasis, and parasitic infection, which all cause chronic inflammation. In contrast, viral hepatitis and metabolic syndrome are more common in the small duct type. […] Approximately 50% of iCCAs have actionable mutations that can be treated with commercially available medications. The most frequently observed alterations are isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations (18.3%) and fibroblast growth factor receptor 2 (FGFR2) fusions (11.6%), followed by ERBB2 (5.1%), and BRAF (5.0%).

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