Intrahepatic cholangiocarcinoma

　　The etiology of intrahepatic cholangiocarcinoma is not yet fully clear. It has been found to be related to the following factors.

　　1. Chronic cholangitis, infection factors

　　Long-term chronic inflammation stimulation is the basis for the occurrence of cholangiocarcinoma, as it has been clinically found that diseases associated with cholangiocarcinoma can all lead to chronic cholangitis. The long-term stimulation of certain substances in bile (such as metabolites of bile acids) on the cholangial mucosa leads to atypical hyperplasia of the epithelium.

　　2. Bile duct, gallbladder stones

　　20% to 57% of bile duct cancer patients have gallstones, thus it is believed that the chronic stimulation of stones may be a carcinogenic factor.

　　3. Ulcerative colitis

　　It has been reported that the incidence of bile duct cancer in patients with ulcerative colitis is 10 times higher than that in the general population, and the onset age of bile duct cancer patients with ulcerative colitis is 20 to 30 years earlier than that of the general population, averaging 40 to 45 years, with a long history of colitis. Chronic bacteremia in the portal venous system may be the cause of bile duct cancer and PSC, and the lesions often involve the entire colon. The association between ulcerative colitis and bile duct cancer may be related to chronic portal venous bacteremia.

　　4. Bile duct cystic malformation (congenital bile duct dilatation)

　　It has become a consensus that congenital bile cysts are prone to canceration. The incidence of bile duct cancer in patients with congenital bile cysts is as high as 2.5% to 28%, and those with cystic malformations have a higher risk of canceration 20 to 30 years earlier than normal individuals, although 75% of cystic malformations appear symptoms in infancy and childhood. However, for the occurrence of bile duct cancer, 3/4 of the patients are those who appear symptoms of bile cystic malformation in adulthood. Regarding the mechanism of bile cystic malformation leading to bile duct cancer, some believe that when the opening of the pancreatic duct into the bile duct is abnormally high, it can cause bile reflux into the bile duct, leading to the malignant transformation of bile duct epithelium. Other factors that may lead to malignancy include bile stasis, stone formation, and chronic inflammation within the cystic cavity.

　　5. Liver fluke (Clonorchis sinensis) infection

　　Infection with Clonorchis sinensis is also considered to be related to the occurrence of bile duct cancer, although Clonorchis sinensis often resides in the intrahepatic bile ducts, it can also reside in extrahepatic bile ducts. The body itself and its metabolic products can cause long-term stimulation of the bile duct mucosal epithelium, leading to bile duct mucosal hyperplasia, producing tumor-like changes and carcinogenesis.

　　6. Biliary surgery history

　　Bile duct cancer can occur many years after surgery, and it can occur in bile ducts without stones, mainly due to chronic biliary infection leading to epithelial metaplasia, often after intraductal drainage surgery.

　　7. Radioactive thorium dioxide

　　Patients with a history of thorium exposure have an earlier onset of bile duct cancer by 10 years compared to those without thorium exposure, with an average latency period of 35 years (after exposure to thorium), and more often occurring at the distal part of the intrahepatic bile duct tree.

　　8. Cholangitis

　　Patients with primary biliary cholangitis (PSC) have a higher chance of developing bile duct cancer than the general population, and PSC is also related to ulcerative colitis.

　　9. Hepatitis B virus infection

　　Some bile duct cancer patients in China have been infected with hepatitis B virus, and the relationship between the two is yet to be further elucidated.

　　10. K-ras gene mutation

　　Recent studies in molecular biology have shown that the mutation rate of the K-ras gene 12 codon in bile duct cancer reaches 77.4%, indicating that K-ras gene mutation may play a relatively important role in the occurrence of bile duct cancer.

　　In addition, it may be related to bile reflux, bile stasis, stone formation, the malignant transformation of benign bile duct tumors, and tumor-like differentiation of liver stem cells, all of which can cause chronic inflammatory stimulation of the bile duct mucosa, leading to the induction of bile duct cancer.

　　Intrahepatic cholangiocarcinoma, if complicated with cholelithiasis and bile duct infection, may have chills, fever, and periodic abdominal pain or dull pain. In the late stage, due to peritoneal invasion or invasion of the portal vein, portal hypertension may occur, leading to ascites. Late-stage patients may develop hepatorenal syndrome.

　　The clinical manifestations of intrahepatic cholangiocarcinoma are mainly progressive jaundice accompanied by upper abdominal discomfort, loss of appetite, weight loss, itching, etc. If cholelithiasis and bile duct infection are present, there may be chills, fever, and periodic abdominal pain or dull pain. If the liver duct cancer is located on one side, it may be asymptomatic at first. When it affects the opening of the opposite liver duct, obstructive jaundice appears. If the middle bile duct cancer is not accompanied by cholelithiasis and infection, it is mostly painless progressive obstructive jaundice. Jaundice usually progresses rapidly without fluctuation, and examination may show liver enlargement, hard texture, and no gallbladder enlargement. If it is at the lower end of the common bile duct, a palpable enlarged gallbladder may be felt. If the tumor ulcerates and bleeds, there may be black stools, positive fecal occult blood test, anemia, and other symptoms.

　　The etiology of intrahepatic cholangiocarcinoma is not yet clear, and its relationship with cholelithiasis is not as close as that of gallbladder cancer. Therefore, the primary prevention of cholangiocarcinoma lacks effective methods, mainly focusing on the prevention and treatment of intrahepatic gallstones and regular systematic health checks.

　　Laboratory tests for intrahepatic cholangiocarcinoma may show significantly elevated total bilirubin, direct bilirubin, alkaline phosphatase, and γ-glutamyl transferase. Alanine aminotransferase is generally slightly abnormal, and this imbalance of bilirubin and alanine aminotransferase elevation helps differentiate from viral hepatitis. Prothrombin time prolongation, and some patients may have elevated CA199 and CEA. In addition, imaging examinations can be performed to help clarify the diagnosis of cholangiocarcinoma, understand the presence of metastatic foci, and assess whether the tumor can be resected. The specifics are as follows.

　　1. Ultrasound imaging examination

　　Ultrasound examination is simple, quick, accurate, and inexpensive, and can detect bile duct dilation both within and outside the liver, showing the site and nature of bile duct obstruction. Ultrasound examination is the first-line examination for obstructive jaundice.

　　2. Percutaneous liver puncture cholangiography (PTC)

　　PTC can clearly show the morphology, distribution, and blocked site of the intrahepatic and extrahepatic bile duct tree. This examination is an invasive procedure, and postoperative hemorrhage and bile leakage are relatively common and severe complications.

　　3. Endoscopic retrograde cholangiopancreatography (ERCP)

　　ERCP is not suitable as a routine examination for cholangiocarcinoma and is even relatively contraindicated. For high-position cholangiocarcinoma, percutaneous liver puncture cholangiography can show the site of cholangiocarcinoma and can also place an internal stent catheter to reduce jaundice. ERCP is of diagnostic significance for lower segment cholangiocarcinoma and helps differentiate from duodenal papillary tumors and pancreatic head cancer.

　　4. CT examination

　　CT can accurately display the site and extent of bile duct dilation and obstruction, with high accuracy in determining the nature of the lesion. Three-dimensional spiral CT cholangiography (SCTC) is trending to replace PTC and ERCP examinations.

　　5. Magnetic Resonance Cholangiopancreatography (MRCP)

　　MRCP examination is a non-invasive bile duct imaging technique. It can show the full picture of the intrahepatic bile duct tree, the blocked location and scope of the tumor, whether there is invasion or metastasis of the liver parenchyma, and it is currently the ideal imaging examination method for cholangiocarcinoma at the hepatic hilum.

　　6. Radionuclide imaging scan

　　Using 99mTc-EHIDA intravenous injection, followed by continuous photography with a γ camera, dynamic images of the bile duct can be obtained, which is harmless to patients and the method is simple.

　　7. Selective hepatic artery and portal vein angiography

　　The main purpose is to understand the relationship and invasion of the portal vein and hepatic artery with the tumor, and help assess the resectability of the tumor before surgery. Digital subtraction angiography (DSA) can show the relationship between the inflow of blood into the liver at the hepatic hilum and the tumor, which is significant for the extensive radical surgery of cholangiocarcinoma.

　　In addition to conventional treatment, patients with intrahepatic cholangiocarcinoma should pay attention to a light diet, drink plenty of water. Patients should also eat a large amount of vegetables and fruits rich in vitamins. Avoid spicy and刺激性 food.

　　The treatment principle for intrahepatic cholangiocarcinoma is surgical resection for early cases, combined with radiotherapy and chemotherapy after surgery to consolidate and improve the effectiveness of surgery. For inoperable advanced cases, bile duct drainage surgery should be performed to control bile duct infection, improve liver function, reduce complications, extend life, and improve quality of life.

　　Surgical resection is the only curative treatment for cholangiocarcinoma, and adjuvant radiotherapy can only improve the survival rate of patients. For inoperable and locally metastatic cholangiocarcinoma, after effective bile duct drainage, radiotherapy can improve the symptoms and prolong life. However, cholangiocarcinoma has always been considered to be a tumor that is not sensitive to radiation. The median survival period reported for radiotherapy is 9 to 12 months.

　　Cholangiocarcinoma is not sensitive to chemotherapy, and the sensitivity to chemotherapy is lower than that of other gastrointestinal tumors such as colon cancer. However, chemotherapy may alleviate the symptoms caused by cholangiocarcinoma, improve the quality of life of patients, and may even prolong survival.