Bile duct cancer or cholangiocarcinoma, (CCA) is a rare cancer with an incidence of ~3 cases per 100,000 with 10,000 new case diagnosed annually. It is about 10-20% of liver cancers.
Interestingly, in Thailand, and some south east asian countries, the incidence is nearly 10 fold higher due to liver fluke infections (Opisthorchis viverrini and Clonorchis sinesis). https://www.cureus.com/articles/185332-associations-of-liver-fluke-infection-and-cholangiocarcinoma-a-scoping-review#!/
It is thought that the eating uncooked or raw fish leads to persistent infection by liver flukes in the bile duct. The damage, over decades, is caused by chronic mechanical damage to the bile duct epithelial cells but also causes release of OvGRN-1 by the parasite. It is thought that proinflammatory IL6 produced chronically can cause damage to the bile duct cells and turn cancerous. However, if liver fluke infection is detected early then it can be targeted by antihelmentic therapy such as Praziquantel or Tribendimidine.
CCA can be detected with Carbohydrate antigen 19-9 as a biomarker which is used as a diagnostic tool. CCA is mostly treated with removal of the tumor through surgery or radiation but chemotherapy is also utilized for tumors that are unresectable, metastatic or recurrent. The efficacy of chemotherapy is unknown though gemcitabine and cisplatin are used as first line treatment to shrink tumors and control spread.
The genes that are usually involved are TP53 (26-45%), KRAS (6-23%), ARID1A involved in chromatin remodeling (6-23%), SMAD4 (8-24%) and SMAD4& CDKN2A/B .
A small percentage (~10%) are actionable with currently available therapies IDH1 with Ivosidenib, FGFR2 with Pemigatinib and BRAF V600E.
