Laboratory tests

Biochemical tests of liver function may reveal a cholestatic picture with elevated total bilirubin and alkaline phosphatase. This pattern is non-specific for cholangiocarcinoma and may be found with any cause of obstruction to bile flow. The levels of blood bilirubin and alkaline phosphatase usually correlate with degree and duration of obstruction of the biliary ducts. Fluctuation in the serum bilirubin level may reflect incomplete obstruction and involvement of one hepatic duct.

CEA and CA19-9
Carcinoembriogenic antigen (CEA) and CA 19-9 are blood tests for non-specific markers of underlying gastrointestinal malignancies. These tests are positive in more than 40% of patients with cholangiocarcinoma, but usually only in late stages of the tumor.

Alpha-Fetoprotein (AFP)

Alpha-fetoprotein is another blood test commonly used to identify markers of possible hepatobiliary malignancy. This test is usually elevated in patients with cholangiocarcinoma, but not to the degree of elevations in patients with hepatocellular carcinoma.

Radiological Diagnosis

Ultrasound
Transabdominal ultrasound is a totally painless, non-invasive procedure. The test does not require special preparation, although it is technically easier in patients with at least six hours of fasting. Transabdominal ultrasound is usually recommended as the first imaging modality for the investigation of patients with suspected cholangiocarcinoma. In hilar cholangiocarcinoma, ultrasound demonstrates bilateral dilation of intrahepatic ducts, and right and left hepatic ducts. In rare cases, the tumor itself can be visualized as either a hypoechoic (decreased echodensity) or hyperechoic (increased echodensity) rounded mass located just distal to dilated biliary ducts. Peripheral cholangiocarcinoma may be suspected if abdominal ultrasound demonstrates local dilation of intrahepatic ducts or isolated dilation of the biliary tree inside one lobe of the liver. In both peripheral and hilar cholangiocarcinoma, biliary ducts distal to the obstruction (common hepatic duct and common bile duct) are not dilated. In patients with hilar cholangiocarcinoma and complete obstruction of both right and left hepatic ducts, extrahepatic bile ducts and the gallbladder appear empty (collapsed) because there is no bile flow out of the liver. In patients with distal cholangiocarcinoma, ultrasound demonstrates dilated intra- and extrahepatic ducts along with significant dilation of the gallbladder. Peripherally located tumors cause segmental or lobular obstruction of the biliary tree. Bile flow from the rest of the liver is preserved. Extrahepatic bile ducts and the gallbladder appear normal (filled with bile) in patients with peripheral cholangiocarcinoma.

Transabdominal ultrasound can also detect the presence of liver metastases as single or multiple rounded lesions of different echogenicity.

Computed Tomography (CT)
Computed tomography may detect lesions of low-density mass associated with dilated biliary ducts (Figures 10 and 11). Similar to transabdominal ultrasound, computed tomography produces different pictures depending on location of the tumor and the level and degree of obstruction. Hilar masses cause bilateral dilation of intrahepatic biliary ducts. Distal tumors produce universal dilation of intra- and extrahepatic bile ducts and gallbladder. Peripheral cholangiocarcinoma may present with atrophy, decreased size of the affected lobe of the liver with minimal dilation of the small intrahepatic ducts. In contrast to hypervascular hepatocellular carcinomas, cholangiocarcinomas are usually hypovascular and appear hypodense or isodense compared to liver parenchyma. Computed tomography is also capable of demonstrating the presence of liver metastases or lymphatic nodules and tumor growth into surrounding organs.

Figure 10. Computed tomography (CT) image showing cholangiocarcinoma in the hilum of the liver.

Figure 11. Comparison of radiographic images showing cholangiocarcinoma; A, computed tomography image; B, cholangiogram (ERCP image). Arrows designate the tumor.

Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging is slightly superior to computed tomography in visualization of tumors. The recent addition of magnetic resonance cholangiography allows visualization of both dilated biliary ducts proximal to the tumor and normal-sized extrahepatic ducts distal to the level of occlusion. Magnetic resonance cholangiography (MRCP) images obtained from the newest diagnostic equipment are comparable in quality to those obtained with Endoscopic Retrograde Cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography. Ductal or intravenous injection of contrast medium is not necessary and the patient is not exposed to irradiation. The MRCP creates an enhanced MRI and may be adjusted to optimally visualize the biliary and pancreatic ducts.

Endoscopic Diagnosis
Gastrointestinal endoscopy allows the physician to visualize and biopsy the mucosa of the upper gastrointestinal tract. Endoscopy permits visualization of the esophagus, stomach and duodenum. The enteroscope allows visualization of at least 50% of the small intestine, including most of the jejunum and different degrees of the ileum. During this procedure, the patient may be administered a pharyngeal topical anesthetic agent that helps to prevent gagging. Pain medication and a sedative may also be administered prior to the procedure. The patient is placed in the supine position on his/her left side (Figure 12).

Figure 12. Room set-up and patient positioning for endoscopic retrograde cholangiopancreatography (ERCP).

Endoscopic Retrograde Cholangiopancreatography (ERCP)
Endoscopic retrograde cholangiopancreatography is an endoscopic procedure that involves the use of fiberoptic endoscopes (Figure 13). The side-viewing endoscope is introduced into the second portion of duodenum, and contrast material is injected into the bile ducts via major duodenal papilla under fluoroscopic guidance (Figure 14). Multiple x-ray pictures are taken to visualize the distribution of the contrast in the biliary tree. Endoscopic retrograde cholangiopancreatography can demonstrate normal diameter and structure of the extrahepatic ducts distal to occlusion and dilated intrahepatic ducts proximal to occlusion (Figure 15).

Figure 13. Side-viewing endoscope.

Figure 14. A, B, Position of the endoscope in the duodenum during ERCP.

Figure 15. A, B, ERCP technique; A, endoscopic injection of contrast medium into biliary ducts; B, cholangiogram (ERCP image) of a normal biliary tree.

Cholangiocarcinoma on ERCP will produce a filling defect or area of narrowing, with irregular borders at the level of occlusion (Figure 16). Spontaneous bleeding from the tumor may cause longitudinal filling defects on ERCP. These blood clots, if not removed, can be misleading in terms of demonstrating the true size and extent of the tumor into the lumen of bile ducts. Samples of tissue from the tumor can be obtained during the procedure by brush or biopsy under fluoroscopic guidance to confirm the diagnosis (Figure 17). ERCP can usually demonstrate the distal level of occlusion. In cases of complete occlusion, ERCP may not be able to evaluate condition of the biliary tree proximal to the tumor. This group of patients would benefit from percutaneous transhepatic cholangiography.

Figure 16. ERCP technique; A, endoscopic injection of contrast medium into biliary ducts with Klatskin’s tumor; B, cholangiogram showing the tumor.

Figure 17. Brush biopsy of a cholangiocarcinoma; A, cholangiogram; B, corresponding illustration showing the brush catheter.

Endoscopic Ultrasound (EUS)
Endoscopic ultrasound is a combination of endoscopy with ultrasound to obtain images within the gastrointestinal tract. The procedure is performed after the patient has been prepared (the same as for standard upper endoscopy). Topical anesthesia and intravenous sedation are administered and the scope is passed through the mouth and into the stomach. The endoscope is then directed to the area of clinical interest. Endoscopic ultrasound has been used for the diagnosis of carcinomas of the bile duct.

Because the common bile duct and gallbladder are in close proximity to the duodenum and distal stomach, EUS has proven to be a useful tool for imaging these organs (Figure 18). This technique has been used to stage carcinomas of the bile duct and the gallbladder.

Figure 18. A, Location of the endoscope in duodenal bulb; B, corresponding cross-sectional view; C, corresponding ultrasound image.

Percutaneous Radiological Diagnosis

Percutaneous Transhepatic Cholangiography
Percutaneous transhepatic cholangiography is an invasive procedure performed by a radiologist under fluoroscopic guidance. A small needle is introduced through the liver into one of the peripheral biliary ducts. Contrast material is injected through the needle and x-ray pictures obtained to document the biliary tree anatomy. In patents with cholangiocarcinoma, percutaneous transhepatic cholangiogram findings are similar to those obtained by ERCP (dilated intrahepatic ducts, normal size extrahepatic ducts, irregular filing defects and strictures at the level of occlusion). If cholangiocarcinoma causes complete obstruction of the biliary tree, percutaneous transhepatic cholangiography is the ideal method to visualize the ducts proximal to obstruction. Bile ducts distal to obstruction may not be visible on percutaneous transhepatic cholangiography in this situation (Figure 19).

Figure 19. A, Technique of transhepatic percutaneous cholangiography; B, corresponding percutaneous cholangiograph (after catheter is introduced).

Angiography
Angiography may be used for pre-operative staging. It is used to evaluate the level of biliary obstruction and to assess resectability and invasion of the portal vein and/or hepatic artery. This procedure detects vascular encasement (seen as gradual narrowing of the vessel with irregular borders), venous obstruction (complete obliteration of the lumen), and also aids in the delineation of anatomy, prior to surgical resection. Angiography is an accurate means of diagnosing mesenteric vascular disease, portal hypertension and gastrointestinal hemorrhage.

Patients are given mild sedatives and an analgesic prior to angiography. During the procedure, blood pressure, electrocardiogram, oxygen saturation and pedal pulses are monitored. There may be some slight discomfort at the puncture site, as well as a burning sensation during contrast injection. The procedure can be safely performed on an outpatient basis. After four hours of observation, patients are ambulated and discharged (often with an attendant).