Cholelithiasis, Cholecystitis, Choledocholithiasis, and Hyperplastic Cholecystoses

Abdominal Radiography

Only about 15% to 20% of gallstones are sufficiently calcified enough to be visualized on conventional abdominal radiographs. Therefore, abdominal radiographs have a limited role in the detection of gallstones. Oral cholecystography was introduced in the 1920s, and for many years it was the primary modality for evaluation of gallbladder disease, including stones. However, this technique has largely been replaced by sonography.

Ultrasound

Sonography is now considered the imaging tool of choice for the detection of gallstones, with a reported accuracy of 96%. However, recent advances in sonographic technology resulting in improved spatial resolution may allow even higher diagnostic accuracy. Other advantages of sonography include the ability to perform studies at the bedside and lack of ionizing radiation. Sonography can also evaluate other structures in the right upper quadrant when alternative diagnoses are under consideration.

At sonography, a gallstone appears as a highly reflective echo that is generally mobile and associated with posterior acoustic shadowing ( Fig. 49.1 ). Both mobility and acoustic shadowing are important features that help differentiate gallstones from other echogenic foci in the gallbladder lumen, such as sludge or solid masses. An aggregate of sludge or sludge ball (also referred to as tumefactive sludge) may be mobile but will not cast an acoustic shadow ( Fig. 49.2 ). A solid mass will not be mobile and will not shadow and may exhibit vascularity on color or spectral Doppler interrogation.

Very small stones may not always cast a shadow. To maximize detection, the highest-frequency transducer possible should be used with the focal zone placed at the level of the stone. In recent years, tissue harmonic imaging has been shown to improve the detection rate of gallbladder calculi ^, ( Fig. 49.3 ).

Stones located in the gallbladder neck or trapped behind a fold may be overlooked when the patient is evaluated only in the supine position. Also, small stones may become more conspicuous when the patient is evaluated in the decubitus or upright position, as they produce a shadow only when they are imaged in aggregate. Therefore, it is always important to evaluate the patient in more than one position in assessing for the presence of gallstones. A follow-up study may be suggested if the clinical index of suspicion is high and the initial examination is negative.

If the gallbladder is contracted and the lumen is filled with shadowing stones, a high-amplitude echo results that is usually linear or curvilinear in configuration and associated with posterior acoustic shadowing. Careful observation will demonstrate a perceivable gallbladder wall separate from the intraluminal stones, sometimes facilitated by the use of a high-resolution linear transducer ( Fig. 49.4 ). This appearance has been called the wall-echo-shadow sign. The main differential diagnostic considerations are a porcelain gallbladder, with calcification in the gallbladder wall, and air in the gallbladder, such as in emphysematous cholecystitis. Correlation with abdominal radiography or computed tomography (CT) can be helpful as a problem-solving tool ( Fig. 49.5 ).

Computed Tomography

The ability to detect gallstones at CT depends on differing density of the stone with respect to bile. The reported sensitivity of CT for detection of gallstones is approximately 75%. Calcified stones are readily identified as they are denser than bile ( Fig. 49.6A ). Stones with high concentration of cholesterol may also be readily identified as these stones are less dense than bile ( Fig. 49.6B ). When stones degenerate, nitrogen gas may collect in central fissures and create the Mercedes-Benz sign. This may be the only visualized evidence of a gallstone and appear as a focal collection of gas in the nondependent gallbladder lumen ( Fig. 49.6C ). Noncalcified pigment stones are soft tissue attenuation density and may be difficult to differentiate from a soft tissue mass ( Fig. 49.6D ). Many stones are composed of a mixture of calcium, bile pigments, and cholesterol and may be similar in density to bile and therefore not visible at CT ( Fig. 49.7 ). The size of the stone is also an important factor determining if a stone is visible at CT. Small stones are frequently missed unless the density differs markedly from bile. Most stones missed prospectively were faintly calcified and were retrospectively detected only as subtle defects within the gallbladder.

Magnetic Resonance Imaging

On T2-weighted magnetic resonance imaging (MRI), gallstones are manifested as signal voids in the high signal intensity bile ( Fig. 49.8 ). Cholesterol stones are generally isointense or hypointense on T1-weighted images, whereas pigment stones have been shown to have high signal intensity on T1-weighted images. This signal hyperintensity is caused by the presence of metal ions in the pigment stones, shortening the T1 relaxation time. Another study of gallstone appearance at MRI also correlated signal intensity with chemical composition. T2-weighted central high signal intensity corresponded to fluid-filled clefts in the stones, whereas central and peripheral high signal areas on T1-weighted images corresponded to fluid clefts as well as regions high in copper content. Other intraluminal filling defects that may mimic gallstones on T2-weighted images include tumor, blood clot, and gas bubbles.

Cholescintigraphy

The hepatic parenchyma is normally observed within 1 minute, with peak activity at 10 to 15 minutes. ^, The bile ducts are usually visible within 10 minutes, and the gallbladder should appear within 1 hour if the cystic duct is patent ( Fig. 49.10A ). If the gallbladder has not been defined, imaging should be performed further up to 4 hours. Prompt biliary excretion of tracer without demonstration of the gallbladder is the hallmark of acute cholecystitis ( Fig. 49.10B ). As noted before, false-positive results may occur in patients with abnormal bile flow because of liver disease or a prolonged fast with distended sludge-filled gallbladder. Also, delayed gallbladder filling can occur in the setting of chronic cholecystitis. If the gallbladder is not visualized after 1 hour and there is visualization of the biliary tree and duodenum, intravenous morphine may be administered, which causes spasm of the sphincter of Oddi, raising pressure within the bile ducts and increasing the likelihood of bile flow into the gallbladder. If the patient has been fasting for more than 24 hours, an oral fatty meal or intravenous cholecystokinin may be administered, resulting in gallbladder contraction so that the gallbladder can empty and then refill.

Ultrasound

The ultrasound findings in acute uncomplicated cholecystitis are well described and include gallstones, sonographic Murphy sign, gallbladder distention, wall thickening, and pericholecystic fluid ( Fig. 49.11A ). The sonographic Murphy sign refers to maximum tenderness during compression with the ultrasound transducer placed directly over the gallbladder. Of these findings, the first two are considered the most specific. In a study by Ralls and colleagues, the sonographic Murphy sign and the presence of gallstones had a positive predictive value of 92% for the diagnosis of acute cholecystitis. It is cautioned that the sonographic Murphy sign may be blunted if the patient has received pain medication before ultrasound evaluation. Furthermore, impaired mental status may preclude evaluation of this sign. Last, the sonographic Murphy sign may be absent in the setting of gangrenous cholecystitis (see later). If it can be demonstrated that a stone is impacted in the gallbladder neck or cystic duct, this is also an important finding that increases the likelihood of acute cholecystitis ( Fig. 49.11B ). To determine that a stone is impacted in the gallbladder neck or cystic duct requires evaluating the patient in the left lateral decubitus or upright position to assess for mobility of the stone.

Less specific ultrasound findings of acute cholecystitis include gallbladder distention, wall thickening, pericholecystic fluid, and the presence of other intraluminal material such as sludge. In most cases of acute cholecystitis, the gallbladder will be distended. An exception to this occurs when acute cholecystitis complicates chronic cholecystitis, when there may be mural fibrosis impeding distention. Also, if there has been free perforation of the gallbladder, it may appear completely collapsed (discussed further later). Diffuse gallbladder wall thickening, measuring more than 3 mm, is present in 50% to 75% of patients with acute cholecystitis but may also be associated with chronic inflammation. Furthermore, gallbladder wall thickening may be associated with many other conditions, including liver disease such as acute hepatitis, ascites, hypoalbuminemia, and alcoholism as well as congestive heart failure, AIDS, and sepsis. In patients with AIDS, cholangiopathy may be related to infection with organisms such as Cryptosporidium. Other causes include adenomyomatosis and gallbladder neoplasm.

In acute cholecystitis, wall thickening is generally diffuse; if it is more focal, a complication such as gangrenous change or another cause, such as neoplasm, should be considered. Pericholecystic fluid is generally associated with more severe cholecystitis and may be associated with perforation or abscess formation. However, this may also be nonspecific, especially in the setting of generalized ascites. Other entities that can clinically mimic acute cholecystitis, such as peptic ulcer disease and pancreatitis, may also be associated with pericholecystic fluid. Sludge, related to bile stasis, can develop in patients with acute cholecystitis due to gallbladder obstruction.

Computed Tomography

Although it is not the first-line imaging modality for the evaluation of suspected acute gallbladder disease, the role of CT in the evaluation of the patient with acute abdominal pain continues to expand. The cause of the patient’s symptoms may initially be unclear because of nonspecific clinical findings. In this setting, CT may be the initial study performed as it allows more comprehensive evaluation of the abdomen and pelvis and can identify other acute inflammatory processes that may simulate acute cholecystitis. Therefore, it is important to become familiar with the spectrum of CT findings in acute cholecystitis. CT is also a useful adjunct to ultrasound when ultrasound findings are equivocal or when a complicated form of cholecystitis is suspected (see later). In a retrospective study at the author’s institution, the overall sensitivity, specificity, and accuracy of CT for the diagnosis of acute cholecystitis were 91.7%, 99.1%, and 94.3%, respectively.

The CT findings of acute cholecystitis include gallstones, gallbladder distention, thickening of the gallbladder wall, pericholecystic inflammation, and fluid ( Fig. 49.12 ). The CT findings of acute cholecystitis have been divided into major and minor criteria. Major findings include calculi, mural thickening of the gallbladder, pericholecystic fluid, and subserosal edema. Minor findings are gallbladder distention and sludge. CT is limited with respect to detection of gallstones as only up to 75% are visualized. Of these signs, the presence of pericholecystic inflammatory change is believed to be the most specific. Gallbladder wall thickening on CT is a nonspecific finding and may be secondary to a broad spectrum of both inflammatory and neoplastic disorders. Gallbladder carcinoma tends to cause greater mural thickening than benign disorders do.

On occasion, it may be difficult to differentiate gallbladder wall thickening from pericholecystic fluid. Pericholecystic fluid tends to be more focal and irregularly marginated, whereas mural thickening is concentric. Punctate foci of contrast enhancement corresponding to enhancing vessels within the gallbladder wall may be observed. A target appearance corresponds to an inner layer of enhancing mucosa and an outer layer of enhancing serosa with hypoattenuating submucosal edema between the two.

An ancillary CT finding of gallbladder inflammation is increased contrast enhancement in the liver parenchyma adjacent to the gallbladder ^, ( Fig. 49.12 ). This finding results from hepatic arterial hyperemia secondary to gallbladder inflammation. Increased density of the gallbladder wall has been described as a finding on unenhanced CT, found in approximately 51% of patients. This is found in patients with mucosal hemorrhage and necrosis and may be a predictor of gangrenous change.

Magnetic Resonance Imaging

Like CT, MRI is usually used in the setting of suspected acute cholecystitis when other imaging findings are equivocal or the clinical setting is ambiguous. Magnetic resonance cholangiopancreatography (MRCP) is sensitive in the diagnosis of choledocholithiasis, which is particularly important if laparoscopic cholecystectomy is performed. In addition to gallstones, MR readily demonstrates gallbladder wall edema, which is manifested as high signal intensity on T2-weighted images. ^, Patients with surgically proved acute cholecystitis had greater than 80% contrast enhancement of the wall, which helped differentiate acute from chronic cholecystitis. A transient increase in hepatic enhancement may be seen around the gallbladder in 70% of cases during the arterial phase of enhancement and, as with CT, may be an important indicator of acute gallbladder inflammation ( Fig. 49.13 ). Altun and colleagues found that increased gallbladder wall enhancement and increased transient pericholecystic hepatic enhancement had the highest combination of sensitivity and specificity for the diagnosis and differentiation of acute and chronic cholecystitis. MR has been shown to be superior to ultrasound for detection of obstructing calculi in the gallbladder neck and the cystic duct. MRI may also be helpful to identify complications of acute cholecystitis.

Ultrasound

The reported sensitivity of ultrasound in acute acalculous cholecystitis (AAC) varies widely from 36% to 92%. ^, Gallstones are not present, and afflicted patients are often insensitive to pain because of altered mental status or medications, thus making the sonographic Murphy sign unreliable. These patients may also have hypoalbuminemia, congestive heart failure, and long-standing parenteral nutrition, all of which are associated with gallbladder wall thickening, distention, and sludge. There is a great degree of overlap in ultrasound findings of intensive care unit patients with AAC and those without. In one study evaluating the ultrasound findings in intensive care unit patients, the majority of patients had some abnormality of the gallbladder. Nevertheless, ultrasound has the advantage of being performed portably at the bedside and remains a reasonable first study for the diagnosis of AAC. Despite limitations, the American College of Radiology appropriateness criteria assign ultrasound the highest ranking for diagnosis of AAC.