1.Etiology The main cause of intrahepatic cholangiocarcinoma in the West is sclerosing cholangitis, and in East Asia, intrahepatic bile duct stones are also one of the main causes. Intrahepatic bile duct stones mainly occur in East Asia, and in China, they mostly occur in the southeast and coastal areas. With the influx of Asian immigrants, the incidence of intrahepatic bile duct stones in Western countries is also on the rise. The most common causes of intrahepatic bile duct stones are infections, most commonly bacterial and parasitic infections. The most common bacteria are Escherichia coli and the most common parasites are Toxoplasma gondii and Ascaris suum. Pathological factors may also contribute to the pathogenesis, such as malnutrition and bacteremia. Intrahepatic bile duct stones combined with recurrent infections are the most common factors leading to bile duct cancer. Repeated infections, chronic irritation of stones, and bile stasis lead to adenomatous hyperplasia of the mucosa, atypical hyperplasia, and finally the development of bile duct cancer. Bile duct cancer caused by bile duct stones is reported to be about 2-10% in foreign countries [5-7]. In China, 0.36-10% were reported [8,9]. However, its incidence is related to geography, age, gender, lifestyle, and diagnostic methods. 2, Clinical features The main clinical manifestation of intrahepatic bile duct stones is recurrent cholangitis, with repeated high fever and chills in patients. There is no special difference between intrahepatic bile duct stones combined with bile duct cancer in early stage and intrahepatic bile duct stones in terms of clinical manifestations, and the preoperative early diagnosis rate is low. However, if the duration of intrahepatic bile duct stones is longer than that, accompanied by liver abscess formation, recent progressive wasting, intractable pain, uncontrollable infection, and progressively worsening jaundice, the possible presence of combined bile duct cancer should be considered. Combined cholangiocarcinoma in the late stage may show disseminated metastasis in the abdominal cavity, pulmonary metastasis, progressive wasting, jaundice, ascites and other manifestations of malignant fluid. The diagnostic rate of intrahepatic choledocholithiasis combined with cholangiocarcinoma is extremely difficult, and the diagnostic rate of imaging examination is only 0-42%. It is difficult to distinguish from bile duct cancer due to recurrent cholangitis forming abscess, biliary tumor and liver lobe atrophy. 4.Serological markers There are no specific serological markers for bile duct stones combined with intrahepatic cholangiocarcinoma. It has no specificity for diagnosis. CA19C9, CEA and CA-125 are the most commonly used serological markers for cholangiocarcinoma. CA19C9: 85% of cholangiocarcinoma is combined with elevated CA19C9. CA19C9 is elevated when obstructive jaundice is present, and if CA19C9 remains elevated after the obstruction is removed, it is often indicative of cholangiocarcinoma. CEA is elevated in about 30% of cholangiocarcinomas, and CA-125 is elevated in 40-50% of cholangiocarcinomas. In addition, some tumor markers such as CA-195, CA-242, DU-PAN-2, IL-6, and trypsinogen-2 may also be altered. 5. Pathological features: intrahepatic bile duct stones combined with bacterial infection, recurrent cholangitis, a vicious cycle of stones and inflammation, resulting in bile duct stricture, bile stasis and mechanical irritation may lead to mucosal epithelial hyperplasia and proliferative cholangitis. Proliferative cholangitis can lead to atypical epithelial hyperplasia, adenomatous hyperplasia, and subsequent carcinogenesis. Hepatobiliary carcinoma can also occur in intrahepatic bile ducts that have been operated on without stones. The broad types of common pathology of intrahepatic bile duct cancer are mass-forming, peripheral infiltrative, and intraluminal growth. The majority of carcinomas occur near stones. All cholangiocarcinomas are adenocarcinomas. Histopathology: The tumor cells are in low columnar, cuboidal rows in vasculature, glandular vesicles, etc., with extensive necrosis, infiltration of fibrofatty tissue, invasion of the cytosol, paracancerous tissue, and chronic cholangitis. The affected bile ducts are narrowed and filled with stones. 6. Treatment modalities for intrahepatic bile duct stones have changed dramatically with the surgeon’s knowledge of the disease. The traditional procedure uses bile duct exploration with T-tube drainage. As the stones in the liver repeatedly drain into the common bile duct, repeated open surgical treatment is performed, and many patients undergo several biliary procedures, and the author has seen patients with up to seven biliary explorations. Patients suffer tremendous physical and psychological damage. In order to solve the recurrent biliary stones, surgeons have carried out biliary-intestinal anastomosis, subcutaneous intestinal loops and other procedures, but none of them can fundamentally solve the pathological basis of intrahepatic bile duct stricture and biliary stasis. Thus, they lay the groundwork for bile duct carcinogenesis. 7.Conclusion Intrahepatic bile duct stones are one of the main causes of intrahepatic bile duct cancer, but the early diagnosis rate is low because intrahepatic bile duct stones combined with bile duct cancer have no special clinical manifestations, and it is pathologically difficult to differentiate between repeated inflammatory stimulation, bile duct fibrosis, combined with liver abscess formation and bile tumor formation by imaging. Therefore surgical resection is also low. It is currently a great challenge for surgeons in both diagnosis and treatment.