A 62-year-old man presents to the emergency room with a complaint of dull epigastric pain. The pain has been present for the past 2 months, but worsened on this night after a large meal. He also reports generalized itching for the past few weeks and an involuntary 10-lb weight loss. His past medical history is significant for hypertension and hyperlipidemia. He has a 50-pack-year smoking history and currently smokes half a pack per day. On examination, he is jaundiced. The abdomen is soft with mild tenderness to palpation in the epigastric region. Laboratory studies are remarkable for a total bilirubin of 10 (direct component 8.5), aspartate aminotransferase (AST) of 160, and alanine aminotransferase (ALT) of 120, with a normal complete blood count (CBC).
History, physical examination, and laboratory tests can accurately identify an extrahepatic cause of biliary obstruction in up to 90% of patients.1 Most commonly, obstruction arises from common bile duct stones or pancreaticobiliary malignancy, although obstruction can less commonly result from metastatic disease or benign, typically inflammatory strictures. Common bile duct (CBD) stones are extremely common, and are present in 10% to 15% of people with gallbladder stones.2 After cholecystectomy, 1% to 2% of patients will present with pain, jaundice, or cholangitis as the result of a retained (or “secondary”) common duct stone. Primary common bile duct stones can also present after cholecystectomy, although these are primarily seen in patients of Asian descent. The incidence of common bile duct stones also increases with age; after age 60, up to a quarter of patients with symptomatic cholelithiasis will also have common bile duct stones.3
Biliary obstruction can also result from either benign or malignant biliary stricture. Malignant strictures arise most commonly from pancreatic cancer or cholangiocarcinoma, although duodenal, gallbladder, or ampullary cancers can also cause obstruction, as can metastatic disease or malignant lymphadenopathy.4 Benign biliary strictures can be difficult to distinguish from malignant disease, but may occur with inflammatory conditions like chronic pancreatitis, primary sclerosing cholangitis, or autoimmune disease. Iatrogenic strictures are also seen in patients who undergo liver transplant or other pancreaticobiliary surgery, including 0.2% to 0.5% of patients who have had a prior cholecystectomy.5
Common bile duct stones are classified as primary, arising within the CBD itself, or secondary, originating in the gallbladder. Primary stones are pigmented stones that are brown in color with a mud-like, friable texture.6 They form when bacterial enzymes hydrolyze bilirubin glucuronides to generate free bilirubin, which precipitates within the duct.3 While primary stones are common in Asian populations, most CBD stones in American patients are secondary, or retained within the duct after passage from the gallbladder. These are generally cholesterol stones.
Obstruction of the common bile duct results in cholestasis, or blocked passage of bilirubin into the intestines. Bilirubin then accumulates within hepatocytes and refluxes back into the bloodstream, causing a conjugated hyperbilirubinemia. This excess bilirubin in the blood is responsible for jaundice, and the lack of bilirubin in the intestines is responsible for pale stools and chronic malabsorption of fat-soluble vitamins (A, D, E, and K). Increased pressure from the obstruction results in the hallmark intrahepatic ductal dilatation and enlarged proximal common bile duct seen on imaging.
While obstruction may present with painless jaundice, it can also present with infection in the setting of bile stasis. Normally, both the gallbladder and common bile duct are sterile. They are, however, in continuity with the intestinal tract, and stagnant bile can result in transmission of enteric bacteria to the normally sterile biliary system. The most commonly cultured bacteria is Escherichia coli, although Klebsiella, Pseudomonas, and Enterobacter are also found.7 When the hydrostatic pressure in the common bile duct increases due to obstruction, the bacteria from the static bile can pass into the systemic circulation. The result is cholangitis, and ultimately biliary sepsis.
The clinical presentation of biliary obstruction depends on the etiology. CBD stones are commonly silent and are identified only incidentally during intraoperative cholangiography or magnetic resonance cholangiopancreatography (MRCP) for other purposes. When they become symptomatic, presentation ranges from intermittent right upper quadrant pain to the classic findings of Charcot’s triad (jaundice, fever, right upper quadrant pain) or Reynolds’ pentad (Charcot’s triad with the addition of shock and altered mental status) when obstruction progresses to cholangitis and sepsis. Other symptoms that are less common include dyspepsia, if an obstructing mass causes gastric outlet obstruction, or diabetes and malabsorption due to pancreatic carcinoma or chronic pancreatitis. Weight loss raises suspicion for malignancy. Classically, pancreatic cancer presents with painless jaundice, although more realistically, up to 87% of patients complain of abdominal pain.3
Notable laboratory values include elevated serum bilirubin, aminotransferases, and alkaline phosphatase. International normalized ratio (INR) may be elevated, as vitamin K absorption depends on bile acid availability.6 Normal serum bilirubin ranges from 0.5 to 1.3; levels above 2 produce jaundice, with yellowing of the eyes and/or skin, as well as light-colored stools and dark urine.3 The hyperbilirubinemia will be a direct elevation, as the liver conjugates appropriately but cannot excrete into the duodenum.
Lab elevations are neither sensitive nor specific for biliary obstruction, and provide little data to determine the etiology of obstruction. However, they can be useful in distinguishing an intrahepatic process from an extrahepatic one; the former tends to impact the transaminases primarily, while the latter produces a more significant elevation on alkaline phosphatase and direct bilirubin. An elevation in the tumor marker CA 19-9 can raise suspicion of pancreaticobiliary cancer; however, it is also associated with benign processes such as acute cholangitis or pancreatitis, and it may, in fact, be elevated in biliary obstruction of any cause.4
The diagnosis of extrahepatic biliary obstruction can be made clinically in more than 90% of cases.1 The level and etiology of obstruction, however, is more challenging to determine, and often requires multiple different imaging studies. The more common etiologies of biliary obstruction are listed in Table 16–1, as well as diagnoses that may mimic biliary obstruction by presenting with similar clinical and laboratory abnormalities.
|Primary sclerosing cholangitis
|Primary biliary cirrhosis
WORKUP AND CHOICE OF IMAGING
The workup of jaundice begins with a full history, physical examination, and laboratory evaluation, which are often sufficient to diagnose an extrahepatic obstruction. The goal of imaging is to further characterize the disease by identifying the level of obstruction and the presence of gallstones versus stricture or mass. Transabdominal ultrasound is the initial imaging test of choice, as it is noninvasive, inexpensive, and readily available.1 The gold standard for pancreaticobiliary evaluation remains endoscopic retrograde cholangiopancreatography (ERCP), which allows for both imaging and tissue diagnosis, with therapeutic intervention if needed. ERCP is the treatment of choice for management of CBD stones as well as palliation of malignant obstructions.1,8 The advantages and disadvantages of different imaging modalities are described in more detail in the following sections; often, diagnosis will require the combination of several of these options. A potential approach to diagnosis is outlined in Figure 16–1.
Diagnostic approach to the patient with obstructive jaundice. CBD, common bile duct exploration; CBDE,; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; LAD, lymphadenopathy; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging.