Biliary Obstruction Workup

Serum bilirubin level

Regardless of the cause of cholestasis, serum bilirubin values (especially direct) are usually elevated. However, the degree of hyperbilirubinemia cannot help reliably distinguish between the causes of obstruction.

Extrahepatic obstruction

This is typically associated with considerable direct and indirect bilirubin elevation. However, in the early phases of obstruction and with incomplete or intermittent obstruction, serum bilirubin levels may only be mildly elevated. Initially, an increase in the conjugated bilirubin level occurs without affecting the unconjugated bilirubin level because obstruction of the CBD prevents excretion of already conjugated bilirubin into the duodenum. Conjugated bilirubin that does reach the intestine is deconjugated by intestinal bacteria. Unconjugated bilirubin, in contrast to the conjugated form, easily crosses the intestinal epithelial barrier into the blood. It accumulates in the blood because the uptake mechanism and the hepatic cells are overburdened by bilirubin that has already been conjugated but cannot be excreted. Therefore, indirect bilirubin levels rise even in persons with obstructive jaundice.

Intrahepatic obstruction

Both conjugated and unconjugated bilirubin fractions may increase in varying proportions. The unconjugated fraction may be increased because of the inability of the damaged cells to conjugate normal amounts of unconjugated serum bilirubin. The increase of the conjugated fraction usually results from metabolic deficiency in the excretory mechanism caused by the inflammatory process of the disease.

Alkaline phosphatase (ALP) level

A membrane-bound enzyme localized to the bile canalicular pole of hepatocytes, ALP is markedly elevated in persons with biliary obstruction. However, high levels of this enzyme are not specific to cholestasis. To determine whether the enzyme is likely to be of hepatic origin, measure gamma-glutamyl transpeptidase (GGT) or 5-prime-nucleotidase. These values tend to parallel the ALP levels in patients with liver disease. GGT is used most commonly. While it is part of the routine evaluation of biliary obstruction, the degree of elevation of ALP cannot be used to reliably discriminate between extrahepatic and intrahepatic causes of biliary obstruction.

Extrahepatic obstruction

ALP levels are elevated in nearly 100% of patients, except in some cases of incomplete or intermittent obstruction. Values are usually greater than 3 times the upper limit of the reference range, and in most typical cases, they exceed 5 times the upper limit. An elevation less than 3 times the upper limit is evidence against complete extrahepatic obstruction.

Intrahepatic obstruction

ALP levels are usually elevated, and they often are less than 3 times the upper limit of the normal reference range. However, 5-10% of patients have a greater degree of elevation.

Levels of serum transaminases

Levels of these are usually only moderately elevated in patients with cholestasis but occasionally may be markedly increased, especially if cholangitis is present.

Extrahepatic obstruction

Usually, serum aspartate aminotransferase (AST) levels are not elevated unless secondary acute parenchymal damage is present. When elevations occur, they are usually only mild to moderate (< 10 times the upper reference limit). However, when extrahepatic obstruction occurs acutely, AST values may quickly rise to more than 10 times the normal value, and then they fall after approximately 72 hours. With time and progressive hepatocyte damage caused by distended biliary ductules, an elevation in AST levels may be observed. A 3-fold or more increase in ALT strongly suggests pancreatitis.

Intrahepatic obstruction

Alanine aminotransferase (ALT) is predominantly found in the liver, and most elevations are due to intrahepatic disease. Although less specific to the liver, the AST level is also elevated in cases of intrahepatic cholestasis. ALT and AST levels are usually elevated to the same degree in patients with viral hepatitis and those with drug-induced liver damage. In association with alcoholic liver disease, cirrhosis, and metastatic lesions to the liver, the AST level is elevated more frequently than the ALT level. In general, AST levels are usually higher than ALT levels.

GGT levels

These levels are elevated in patients with diseases of the liver, biliary tract, and pancreas when the biliary tract is obstructed. Levels parallel the levels of ALP and 5-prime-nucleotidase in conditions associated with cholestasis. The extreme sensitivity of GGT, as opposed to ALP, limits its usefulness; however, the level helps distinguish hepatobiliary disease as the cause of an isolated rise in ALP.

Prothrombin time (PT)

This may be prolonged because of malabsorption of vitamin K. Correction of the PT by parenteral administration of vitamin K may help distinguish hepatocellular failure from cholestasis. Little or no improvement occurs in patients with parenchymal liver disease.

Hepatitis serology

Because differentiating viral hepatitis from extrahepatic obstructive causes may be difficult, include serologic assays for acute viral hepatitis B and C in the investigation of all patients with cholestasis.

Antimitochondrial antibody levels

The presence of antimitochondrial antibodies, usually in high titers, is indicative of PBC. They are usually absent in patients with mechanical biliary obstruction or PSC.

Urine bilirubin levels

Urine bilirubin normally is absent. When it is present, only conjugated bilirubin is passed into the urine. This may be evidenced by dark-colored urine seen in patients with obstructive jaundice or jaundice due to hepatocellular injury. However, reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus, urine bilirubin may be found even in the absence of hyperbilirubinemia or clinical jaundice.

Plain radiographs are of limited utility to help detect abnormalities in the biliary system. Frequently, calculi are not visualized because few are radiopaque.

Ultrasonography (US)

Ultrasonography is the least expensive, safest, and most sensitive technique for visualizing the biliary system, particularly the gallbladder. Current accuracy is close to 95%.

This is the procedure of choice for the initial evaluation of cholestasis and for helping differentiate extrahepatic from intrahepatic causes of jaundice. Extrahepatic obstruction is suggested by the presence of dilated intrahepatic bile ducts, but the presence of normal bile ducts does not exclude obstruction that may be new or intermittent.

Visualization of the pancreas, kidney, and blood vessels is also possible.

Ultrasonography is considered somewhat limited in its overall ability to help detect the specific cause and level of obstruction. US is not as useful for CBD stones (bowel gas may obscure visualization of the CBD). The cystic duct is also poorly imaged. In addition, it is less useful diagnostically in individuals who are obese.

Computed tomography (CT) scanning

Traditional CT scanning

Traditional CT scanning is usually considered more accurate than US for helping determine the specific cause and level of obstruction. In addition, it helps visualize liver structures more consistently than US. The addition of intravenous contrast helps differentiate and define vascular structures and the biliary tract.

CT scanning has limited value in helping diagnose CBD stones because many of them are radiolucent and CT scanning can only image calcified stones. It is also less useful in the diagnosis of cholangitis because the findings that specifically suggest bile duct infection (increased attenuation due to pus, bile duct wall thickening, and gas) are seen infrequently.

Lastly, CT scanning is expensive and involves exposure to radiation, both of which lessen the routine use CT scans compared to US examinations.

Spiral CT scanning

Spiral (helical) CT scanning improves biliary tract imaging by providing several overlapping images in a shorter time than traditional CT scanning and by improving resolution by reducing the presence of respiratory artifacts.

CT cholangiography by the helical CT technique is used most often to image the biliary system and makes possible visualization of radiolucent stones and other biliary pathology. ^[9]

Limitations of helical CT cholangiography include reactions to the contrast, which are becoming less frequent. Also, as serum bilirubin levels increase, the ability to visualize the biliary tree diminishes and the ability to fully delineate tumors decreases. Patients are required to hold their breath while images are acquired.

Magnetic resonance cholangiopancreatography (MRCP)

MRCP is a noninvasive way to visualize the hepatobiliary tree. It takes advantage of the fact that fluid (eg, that found in the biliary tree) is hyperintense on T2-weighted images. The surrounding structures do not enhance and can be suppressed during image analysis. However, in its early stages, it was limited in its ability to detect nondilated bile ducts. The advent of rapid acquisition with relaxation enhancement (RARE) sequences and half-Fourier RARE (also known as half-Fourier acquisition single-shot turbo spin-echo or HASTE) sequences can reduce imaging time to a few seconds. This can facilitate imaging in different patient positions to distinguish air from a stone.

Note the following:

• As with helical CT scanning, MRCP gives radiologists the ability to analyze source images and 2- and 3-dimensional projections. Although some techniques require patients to hold their breath for the highest quality images, the time required to complete the scan is decreasing as imaging techniques improve, and alternative procedures capture images between patient breaths.

• MRCP provides a sensitive noninvasive method of detecting biliary and pancreatic duct stones, strictures, or dilatations within the biliary system. It is also sensitive for helping detect cancer. MRCP combined with conventional MR imaging of the abdomen can also provide information about the surrounding structures (eg, pseudocysts, masses).

• While ERCP and MRCP may be similarly effective in detecting malignant hilar and perihilar obstruction, MRCP has been shown to be better able to determine the extent and type of tumor as compared to ERCP. In addition, unlike ERCP, MRCP does not require contrast material to be injected to visualize the ductal system, thereby avoiding the morbidity associated with injected contrast.

• The limitations of MRCP include the contraindications to magnetic resonance imaging. Absolute contraindications include the presence of a cardiac pacemaker, cerebral aneurysm clips, ocular or cochlear implants, and ocular foreign bodies. Relative contraindications include the presence of cardiac prosthetic valves, neurostimulators, metal prostheses, and penile implants.

• Fluid stasis in the adjacent duodenum or in ascitic fluid may produce image artifacts on MRCP, making it difficult to clearly visualize the biliary tree.

• The risk of MRCP during pregnancy is not known.

• Although MRCP currently does not have the capability for the therapeutic applications of the more invasive ERCP, it can be useful for diagnostic purposes and poses less risk to the patient as compared to ERCP.

Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP is an outpatient procedure that combines endoscopic and radiologic modalities to visualize both the biliary and pancreatic duct systems. Endoscopically, the ampulla of Vater is identified and cannulated. A contrast agent is injected into these ducts, and x-ray images are taken to evaluate their caliber, length, and course.

It is especially useful for lesions distal to the bifurcation of the hepatic ducts. Besides being a diagnostic modality, ERCP has a therapeutic application because obstructions can potentially be relieved by the removal of stones, sphincterotomy, and the placement of stents and drains. The addition of cholangioscopy to the ERCP, by advancing a smaller "baby" scope through the endoscope into the common duct, allows for biopsies and brushings within the ducts and better identification of lesions seen on cholangiogram.

ERCP has a limited capacity to image the biliary tree proximal to the site of obstruction. Also, it cannot be performed if altered anatomy prevents endoscopic access to the ampulla (eg, Roux loop).

Complications of this technique include pancreatitis, perforation, biliary peritonitis, sepsis, hemorrhage, and adverse effects from the dye and the drug used to relax the duodenum. The risk of any complication is less than 10%. Severe complications occur in less than 1%.

The sensitivity and specificity of ERCP are 89-98% and 89-100%, respectively. ERCP is still considered the criterion standard for imaging the biliary system, particularly if therapeutic intervention is planned.

Percutaneous transhepatic cholangiogram (PTC)

PTC is performed by a radiologist using fluoroscopic guidance. ^[10] The liver is punctured to enter the peripheral intrahepatic bile duct system. An iodine-based contrast medium is injected into the biliary system and flows through the ducts. Obstruction can be identified on the fluoroscopic monitor. It is especially useful for lesions proximal to the common hepatic duct.

The technique is not easy and requires considerable experience. More than 25% of attempts fail (most often when the ducts cannot be well visualized because they are not dilated, ie, not obstructed.)

Complications of this procedure include the possibility of allergic reaction to the contrast medium, peritonitis with possible intraperitoneal hemorrhage, sepsis, cholangitis, subphrenic abscess, and lung collapse. Severe complications occur in approximately 3% of cases.

The accuracy of PTC in elucidating the cause and site of obstructive jaundice is 90-100% for causes within the biliary tract. The biliary tree can be successfully visualized in 99% of patients with dilated bile ducts and in 40-90% if the bile ducts are not dilated. Still, ERCP is generally preferred, and PTC is reserved for use if ERCP fails or when altered anatomy precludes accessing the ampulla.

Both ERCP and PTC are less frequently used for diagnosis (MRC is preferred) and are more commonly used for therapeutic intervention.

Endoscopic ultrasound (EUS)

EUS combines endoscopy and US to provide remarkably detailed images of the pancreas and biliary tree. It uses higher-frequency ultrasonic waves compared to traditional US (3.5 MHz vs 20 MHz) and allows diagnostic tissue sampling via EUS-guided fine-needle aspiration (EUS-FNA). ^[11]

Although endoscopic retrograde cholangiography is the procedure of choice for biliary decompression in obstructive jaundice, biliary access is not always achievable, in which case, interventional endoscopic ultrasound-guided cholangiography (IEUC) may offer an alternative to percutaneous transhepatic cholangiography (PTC). Maranki et al reported their 5-year experience with IEUC in patients who had unsuccessful treatment with ERCP. ^[12] The investigators used either a transgastric-transhepatic or transenteric-transcholedochal approach to the targeted biliary duct, then advanced a stent over the wire into the biliary tree. ^[12]

Of the 49 patients who underwent IEUC, the cause of biliary obstruction was a malignancy in 35, whereas 14 had a benign etiology. ^[12] Forty-one of the 49 patients (84%) had successful overall therapy with IEUC, with an overall complication rate of 16%. Resolution of obstruction had an 83% success rate (n = 29). The transenteric-transcholedochal approach was used in 14 patients, with successful biliary decompress in 86% (n = 12). ^[12] No procedure-related deaths were reported. Thus, overall, the intrahepatic approach was successful in 73% (29/40) of cases, and the extrahepatic approach was successful in 78% (7/9) cases. ^[12]

An international multicenter retrospective analysis found comparable short-term outcomes between EUS-guided biliary drainage and ERCP in 208 patients with malignant distal common bile duct obstruction who required the placement of self-expandable stents. ^[13] Ninety-seven of 104 patients (94.23%) who underwent EUS-guided biliary drainage and 98 of 104 patients (93.26%) who underwent ERCP had successful stent placement (P = 1.00); each group had an 8.65% frequency of adverse events, and the mean procedural times were similar (35.95 mins vs 30.10 mins, respectively; P = 0.05). However, the rates of postprocedure pancreatitis were higher in the ERCP group (4.8% vs 0%, P = 0.059). ^[13]

EUS has been reported to have up to a 98% diagnostic accuracy in patients with obstructive jaundice. This makes ERCP unnecessary in patients who are found to not have extrahepatic obstruction. In addition, those patients who may require operative biliary drainage are reliably identified and similarly need not undergo ERCP for further evaluation. ^[14]

EUS provides highly detailed imaging of the pancreas. The sensitivity of EUS for the identification of focal mass lesions has been reported to be superior to that of CT scanning, both traditional and spiral, particularly for tumors smaller than 3 cm in diameter.

Compared to MRCP for the diagnosis of biliary stricture, EUS has been reported to be more specific (100% vs 76%) and to have a much greater positive predictive value (100% vs 25%), although the two have equal sensitivity (67%).

Neither transabdominal US nor CT scanning can help reliably exclude the presence of choledocholithiasis. ERCP is highly accurate for this diagnosis but, because of the associated risk of pancreatitis, is generally reserved for patients with known common duct stones. EUS has been reported to have sensitivity approximately equal to both ERCP and MRCP for the detection of common duct stones, with minimal risks directly associated with the procedure.

EUS is more portable than ERCP or MRCP and is useful for patients in the intensive care unit. EUS (if performed in the fluoroscopy suite) can be followed immediately by therapeutic ERCP, which saves time.

The positive yield of EUS-FNA for cytology in patients with malignant obstruction has been reported to be as high as 96%.

PET CT is used to detect distant metastases and staging laparoscopy may be useful to detect small surface peritoneal deposits.