Cholangiocarcinoma is a malignant tumor of the bile ducts. The symptoms of the disease are mainly associated with cholestasis (jaundice, itching of the skin), and patients may also experience pain in the right hypochondrium, a sharp loss of body weight. Ultrasound of abdominal organs, computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), percutaneous cholangiography, determination of cancer markers in the blood are used for diagnosis. The main method of treating cholangiocarcinoma is operative. Chemotherapy and radiotherapy are used in combination with surgery or as palliative treatment.
C22.1 Cancer of the intrahepatic bile duct
Cholangiocarcinoma is a malignant neoplasm that develops from the epithelial cells of the bile ducts. It is found on all continents, but is more common in Southeast Asia. The frequency of detection of cholangiocarcinoma in Europe and North America is 1-3 cases per 100 thousand population, in Japan – 5.5 cases, in Israel about 7 cases. Cholangiocarcinoma accounts for approximately 3% of all malignant diseases of the gastrointestinal tract.
Despite the fact that the tumor is not very common, this problem is quite relevant. The prognosis for this pathology is very unfavorable. To date, the cure of cholangiocarcinoma is possible only if the process is detected at an early stage. The primary diagnosis is most often carried out by a gastroenterologist, since it is to him that patients first turn. Surgeons and oncologists are engaged in treatment.
The etiology of cholangiocarcinoma has not been fully elucidated. Risk factors include gallstone disease, congenital malformations of the biliary tract. The high incidence in Asian countries is explained by the prevalence of parasitic diseases in this territory, such as opisthorchiasis and clonorhosis.
Many experts note an increase in the frequency of malignant tumors of the biliary tract in patients with primary sclerosing cholangitis, chronic inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis. Cholangiocarcinoma is also associated with exposure to toxic substances, such as thorium dioxide, which is used as an X-ray contrast agent. The link between hepatitis C and cholangiocarcinoma has not been fully established.
Presumably, tumors are formed due to damage to the epithelial cells of the biliary tract (mechanical or toxic). According to the histological structure, most of them are adenocarcinoma (a tumor developing from glandular tissue), only 10% are identified as squamosocarcinoma (squamous cell carcinoma). According to its structure, cholangiocarcinoma is dense, glandular structure, white in color, sometimes differs little from areas affected by sclerosing cholangitis.
By localization, the following types of cholangiocarcinomas are distinguished: intrahepatic, extrahepatic in the area of bifurcation of the common bile duct (the most frequent localization), extrahepatic distal tumors that occur on the segment between the vater papilla and the upper edge of the pancreas.
In addition, the TNM system is used for classification, where T (tumor) determines the depth of tumor germination, N (nodulus) – the presence or absence of metastases in regional lymph nodes, M (metastasis) – the presence or absence of distant metastases.
The size and extent of the spread of the tumor process:
- Tx – tumor cannot be evaluated;
- T0 – there are no signs indicating the presence of a tumor;
- Tis – carcinoma or tumor in situ (in situ);
- T1 – the tumor is limited to the bile ducts, grows into the smooth muscle layer and into the fibrous;
- T2a – the spread of the tumor beyond the bile ducts and surrounding tissue;
- T2b – spread of the tumor to nearby hepatic tissues;
- T3 – spread of the tumor to the hepatic arteries and portal vein;
- T4 – tumor germination of the hepatic ducts or involvement of nearby veins and arteries in the process.
Involvement of lymph nodes: Nx – it is impossible to assess the degree of involvement of regional lymph nodes in the process; N0 – there are no metastases in regional lymph nodes; N1 – there are metastases in different regional lymph nodes that are located along the veins, bile ducts and arteries of the abdominal cavity; N2 – lymph nodes are affected along the upper mesenteric arteries or along the abdominal artery, near other abdominal organs. Assessment of metastases: Mx – it is unknown or impossible to determine whether there are metastases; M0 – there are no metastases in the patient; M1 – distant metastases have been identified.
According to the nature of growth, cholangiocarcinoma is classified as follows:
- infiltrative (manifested by diffuse germination of the walls of the bladder and surrounding tissues);
- polypoid (grows in the lumen of the ducts, often has a thin leg);
- exophytic (grows on the outside of the bile ducts);
- mixed (has characteristics of all the above types).
The first symptoms are usually associated with obstruction of the bile ducts. The patient complains of yellowing of the skin, itching. Often there is a darkening of urine and discoloration of feces. Due to impaired fat absorption, patients lose weight. Weight loss may also be associated with a lack of appetite, nausea, vomiting, cancer intoxication. In the later stages of the disease, pain appears in the right hypochondrium.
Cholangiocarcinoma can be complicated by cholangitis (inflammation of the bile ducts). Patients have fever, fever symptoms appear. If the tumor has arisen against the background of sclerotic processes or with cholelithiasis, there is a deterioration in the patient’s condition. Pain, jaundice, itching increase, weakness, nausea, decreased appetite appear.
The symptoms of cholangiocarcinoma are not specific. It is almost impossible to make a diagnosis solely on the basis of anamnesis and examination. Instrumental and laboratory methods are used to refine the data:
- Biochemical analyses. Conventional biochemical tests of the liver provide information about the degree of dysfunction of this organ, but do not allow for an accurate diagnosis of cholangiocarcinoma. In the blood, an increase in bilirubin is detected due to the direct fraction, alkaline phosphatase. Alanine aminotransferase and aspartate aminotransferase, albumin levels are usually within normal limits.
- Cancer markers. Specific markers of oncological diseases are of greater importance for the diagnosis of cholangiocarcinoma. Patients are diagnosed with the CA 19-9 antigen, although an increased level of it can also be observed in pancreatic cancer or cholangitis. A significant increase in the antigen to 100 U/ml or more in patients with chronic cholangitis is most likely evidence in favor of cholangiocarcinoma. Sometimes it is possible to detect an increase in carcinoembryonic antigen; alpha-fetoprotein is within the normal range.
- Echography. Most often, ultrasound of the liver and gallbladder is used to diagnose cholangiocarcinoma at the initial stage of examination. This method allows you to identify large tumors, the expansion of ducts in some areas. Dopplerometry of liver vessels determines changes in blood flow, which indicate the presence of a neoplasm. Tumors of small size are often not visualized.
- Tomography. Computed tomography (CT) of the biliary tract is somewhat more informative. It helps to detect an increase in lymph nodes, to see smaller tumors. MSCT of the abdominal organs determines the level of obstruction of the biliary tract. Advanced positron emission tomography makes it possible to see tumors smaller than 1 centimeter of nodular type. But using this technique, it is difficult to identify infiltration forms of cholangiocarcinoma.
- Contrast radiography. To clarify the diagnosis, some radiographic research methods are also used. Endoscopic retrograde cholecystography is performed to identify the site of obstruction, pathological changes in the area of the fater papilla. The method allows you to take material for histological analysis. Percutaneous transhepatic cholangiography is performed before surgery. It helps to identify cholangiocarcinoma at the site of bifurcation of the common bile duct.
- MRI. The most informative method today is magnetic resonance imaging (MRI) of the liver and biliary tract. The method is non-invasive, does not require the introduction of contrast, therefore, it is quite safe. MRI of the liver allows you to see the bile ducts and vascular structures in a three-dimensional image, identify small tumors, correctly assess the extent of the lesion, determine the tactics of surgery and further prognosis for the patient.
The disease has to be differentiated with acute viral hepatitis, leptospirosis, cholangitis, stones or sclerotic processes in the gallbladder, cirrhosis of the liver, pancreatic head cancer.
The main method of treating cholangiocarcinoma is operative, although it is not indicated in all cases. If the size of the tumor is small, and it does not germinate the walls of the bile ducts, a choledochotomy is performed. In more difficult situations, resection of the liver lobe (lobectomy) is indicated. A large tumor with damage to nearby structures requires more radical intervention. In such cases, Whipple surgery is performed: part of the liver, stomach and duodenum, gallbladder with ducts, pancreas and regional lymph nodes are removed.
Conservative treatment of cholangiocarcinoma is carried out after surgery or in cases where the operation cannot be performed (palliative therapy). It includes chemotherapy and radiation therapy. For chemotherapy, 5-fluorouracil is most often used. They also conduct courses with gemcitabine, cisplatin.
Prognosis and prevention
The prognosis for cholangiocarcinoma is unfavorable. On average, the survival rate of patients is 14 months. If the tumor is detected on time, thanks to treatment, the patient’s life can be continued for up to three or even up to five years. But since the disease is almost asymptomatic in the initial stage, cases of early diagnosis are rare.
The basis for the prevention of cholangiocarcinoma is adequate treatment of those diseases that can lead to malignant degeneration. These are gallstones, sclerotic processes, helminthiasis, chronic inflammatory diseases of the large intestine.