Bile Duct Cancer (Cholangiocarcinoma)

Symptoms

In the early stages, the disease proceeds without symptoms. In the future, the main signs of cholangiocarcinoma are jaundice (yellowing of the skin and white of the eyes, darkening of urine, discoloration of feces) and itching that develops against its background. These manifestations occur in 90% of cases.
Other symptoms of cholangiocarcinoma are:
•    Fatigue;
•    Nausea;
•    Weight loss;
•    Right hypochondrium discomfort and pain;
•    An increase in the volume of the abdomen (due to a tumor that can be felt, or ascites - accumulation of fluid in the abdominal cavity);
•    Bone pain (with metastases).
All these symptoms are not specific, i.e., they can occur with other diseases.
Another symptom of the disease is an increase in temperature up to 39ºc. This symptom is observed in cholangitis and tumor decay. It occurs after a while due to a lack of nutrients in the central part of the tumor, which must be supplied to it through the emerging vascular network. However, new vessels are formed more slowly compared to the rate of reproduction of cancer cells. As a result, starving cells die, disintegrate and lead to the gradual formation of a cavity in which the decay process slowly proceeds.

Causes

The exact cause of cholangiocarcinoma is unknown. The risk of its formation increases in the presence of the following diseases:
•    Primary sclerosing cholangitis is a chronic liver disease of unknown origin, characterized by inflammation, sclerosis of the intra- and extrahepatic bile ducts, often manifested by jaundice;
•    Ulcerative colitis - a persistent inflammation of the colon characterised by ulcer development.
•    Choledochal cysts - saccular dilatations of the bile duct
•    Caroli's disease is a congenital disease in which multiple intrahepatic biliary cysts are formed;
•    Adenomas - various benign tumors;
•    Multiple papillomatosis of hepaticocholedochus - a benign formation of the bile duct, usually manifested by jaundice;
•    Biliodigestive anastomoses - connections between the bile duct and the intestine that arose after surgery;
•    Liver damage by parasites - flukes opisthorchis viverrini (cause opisthorchiasis ) and clonorchis sinensis (cause clonorchiasis);
•    Lynch syndrome is a hereditary pathology that contributes to the development of colon cancer;
•    Crohn's disease is a severe chronic pathology associated with damage to the mucous membranes of the gastrointestinal tract;
•    Smoking , alcohol;
•    Cirrhosis of the liver ;
•    Exposure to the radiopaque substance thorotrast;
•    Deficiency of liver protein alpha-1-antitrypsin;
•    Hepatitis b , c ;
•    Hiv infection ;
•    Diabetes ;
•    Liver hepatosis 

Treatment

The choice of treatment tactics depends on the localization of the tumor, the stage of its development, the presence of liver cirrhosis and other concomitant pathologies.
The standard treatment for cholangiocellular carcinoma is surgery. If there are contraindications to surgery (severe concomitant diseases, distant metastases, technical impossibility to perform the operation, etc.), Chemotherapy and Radiotherapy are indicated
 Surgical treatment

Drainage of the bile ducts
This intervention is carried out in an operating room: a puncture (puncture) of the bile duct is performed through the liver under ultrasound control and a drainage (tube) is installed for the outflow of bile.
Radical surgical treatment
Radical surgery - complete removal of the neoplasm within healthy tissues - with cholangiocellular cancer can be performed in 10-85% of cases. The presence of distant metastases in the lymph nodes and organs is a contraindication to this method of treatment.
The amount of surgery depends on the location of the tumor.
Chemotherapy
None of the chemotherapeutic agents has convincingly proven effective against cholangiocarcinoma. When using the anticancer drug 5-fu (5-fluorouracil), the body responds to treatment in less than 15% of cases. Other agents such as doxorubicin , mitomycin c , cisplatin , used alone or in combination with 5-fu, have also not been shown to be effective.
Radiation therapy
Studies have not shown a positive effect of adjuvant radiotherapy after surgery. At the same time, some authors recorded an improvement in survival rates in patients who underwent non-radical surgery followed by radiation therapy.

Tests Required for Diagnosis

The symptoms of cholangiocarcinoma are not specific. It is almost impossible to make a diagnosis solely on the basis of history and examination. To clarify the data, instrumental and laboratory methods are used:

•    Biochemical analyses. Routine biochemical tests of the liver provide information on 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 the normal range.

•    Tumor markers. More important for the diagnosis of cholangiocarcinoma are specific markers of cancer. In patients, the ca 19-9 antigen is detected, although its elevated level can also be observed in pancreatic cancer or cholangitis. A significant increase in antigen up to 100 u / ml or more in patients with chronic cholangitis is most likely in favor of cholangiocarcinoma. Sometimes it is possible to detect an increase in carcinoembryonic antigen; alpha-fetoprotein within normal limits.

•    Echography. Most often, ultrasound of the liver and gallbladder is used to diagnose cholangiocarcinoma at the initial stage of the examination. This method allows you to identify large tumors, expansion of the ducts in some areas. Dopplerometry of the liver vessels determines changes in the blood flow, which indicate the presence of a neoplasm. Small tumors are often not visualized.

•    Tomography. Computed tomography (ct) of the biliary tract is somewhat more informative. It helps to identify enlarged 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 methods of research are also used. Endoscopic retrograde cholecystography is performed to identify the site of obstruction, pathological changes in the region of the papilla of vater. The method allows you to take material for histological analysis. Percutaneous transhepatic cholangiography is performed before surgery. It helps to identify cholangiocarcinoma at the bifurcation site 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 degree of damage, determine the tactics of the operation and further prognosis for the patient.

The disease has to be differentiated from acute viral hepatitis , leptospirosis , cholangitis, stones or sclerotic processes in the gallbladder, cirrhosis of the liver, pancreatic head cancer .

Useful info

According to localization, the following types of cholangiocarcinoma are distinguished: intrahepatic, extrahepatic in the bifurcation of the common bile duct (the most common localization), extrahepatic distal tumors that occur in 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 identified
•    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 boundaries of the bile ducts, grows into the layer of smooth muscles and fibrous;
•    T2a - spread of the tumor beyond the bile ducts and surrounding tissue;
•    T2b - spread of the tumor to nearby liver tissues;
•    T3 - spread of the tumor to the hepatic arteries and portal (portal) vein;
•    T4 - tumor invasion 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 various regional lymph nodes, which are located along the veins, bile ducts and arteries of the abdominal cavity; 

N2 - affected lymph nodes along the upper mesenteric arteries or along the celiac artery, near other abdominal organs. 

metastasis score : 

Mx - unknown or impossible to determine if there are metastases; 
M0 - the patient has no metastases; 
M1 - distant metastases were detected.

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 stem);

•    Exophytic (sprouts to the outside of the bile ducts);

•    Mixed (has the characteristics of all of the above types).