Treatment of Gallstone Disease

Patient Selection

Selection of patients for oral dissolution therapy is a function of the stage of gallstone disease, gallbladder function, and characteristics of the stones. Selection criteria are summarized in Box 66.1 . Oral dissolution therapy should be considered for patients with uncomplicated gallstone disease, including those with mild, infrequent biliary pain. Patients with asymptomatic gallstones should not be treated with either dissolution therapy or surgery because the natural history of most asymptomatic stones is to remain asymptomatic. Patients with severe or frequent biliary pain and patients with complications of gallstones, including cholecystitis, pancreatitis, and cholangitis, should not be treated with oral dissolution therapy; these patients should be referred for surgery as soon as possible (see later). In addition, the gallbladder must function, and the cystic duct must be patent to allow unsaturated bile and stones to clear from the gallbladder. The patency of the cystic duct has generally been evaluated by oral cholecystography. More recently, stimulated cholescintigraphy and functional US have been used. These latter modalities assess cystic duct patency as well as gallbladder function.

The characteristics of the stones play an important role in determining the efficacy of dissolution treatment. Oral dissolution therapy works only on cholesterol stones. Although verifying the composition of gallstones can be difficult, the appearance of stones on plain films or CT images can be useful. Cholesterol stones are radiolucent on plain films, and they are hypodense or isodense to bile and lack stone calcification on CT images. During oral cholecystography, the specific gravity of cholesterol stones is less than or equal to that of contrast-enriched bile, thereby resulting in stone buoyancy. The number of stones does not influence the success of oral dissolution therapy; however, only patients with stones that occupy less than half of the gallbladder volume should be considered for treatment. Although oral dissolution therapy has been effective in stones up to 10 mm in diameter, results are best in stones less than 5 mm in size. The ideal stones for oral dissolution treatment are shown in Fig. 66.1 .

Therapeutic Regimens

UDCA (ursodiol) is the preferred drug for oral dissolution treatment. It is taken in a dose of 10 to 15 mg/kg of body weight per day. Nighttime dosing is more effective and is associated with better patient adherence than mealtime dosing. Unlike chenodeoxycholic acid (chenodiol), UDCA is well tolerated and has no important side effects. Treatment should continue until stone dissolution is documented by 2 consecutive negative ultrasonograms at least 1 month apart. Treatment should be stopped if the patient does not tolerate the drug or experiences a complication of gallstones during therapy or if the stones fail to dissolve after 6 months or dissolve only partially after 6 months with lack of progression to complete dissolution by 2 years.

Efficacy

With UDCA, complete dissolution is achieved in 20% to 70% of patients. The variability in the reported response rates is a function of differences in patient selection, doses of bile acid, treatment times, and diagnostic techniques used to document stone dissolution. A meta-analysis of all randomized trials of dissolution treatment showed stone dissolution in 37% of patients. The frequency of stone dissolution was 29% for stones larger than 10 mm, 49% for stones smaller than 10 mm, and 70% for stones less than 5 mm. The time to resolution varies among patients, with a median rate of 0.7 mm per month. Improvement in symptoms occurs before stones have dissolved completely. In addition, long-term treatment has been reported to decrease the risk of biliary pain and acute cholecystitis, independent of gallstone dissolution. Despite initial dissolution of stones in properly selected patients, the rate of gallstone recurrence after oral dissolution therapy is 50% after 5 years, with most recurrences within the first 2 years. This observation illustrates that other factors relevant to gallstone formation, such as gallbladder stasis and superinfection, are not addressed by dissolution treatment. The risk of recurrence is lower in patients with a solitary stone than in those with multiple stones.

Patient Selection

Because shock-wave lithotripsy is usually combined with oral dissolution therapy, patient selection criteria for shock-wave lithotripsy are similar to those for oral dissolution treatment and are summarized in Box 66.2 . Gallbladder function and cystic duct patency are required and are demonstrated by oral cholecystography, functional US, or stimulated cholescintigraphy. Lithotripsy should be considered only for patients with mild, uncomplicated biliary pain. Pregnant patients and patients on anticoagulants should not undergo lithotripsy. Shock-wave lithotripsy is reserved for patients with a solitary stone, measuring less than 2 cm in size. Because only cholesterol stones are reliably cleared by the addition of oral dissolution therapy, stones should have imaging features, such as radiolucency, suggestive of cholesterol stones.

Therapeutic Approach

Patients are usually given sedatives and analgesics or anesthetized and placed in the prone position to minimize the distance between the energy source and the stones and to eliminate interference from intestinal gas and the costal margin. Targeting and monitoring for fragmentation are accomplished with US. Multiple treatment sessions are often required to achieve maximum pulverization. Factors that predict the success of lithotripsy include the degree of fragmentation and gallbladder emptying. Fragmentation depends on stone characteristics and the dose of the shock wave. Important stone characteristics include the size and number of stones as well as their structure and the presence of calcification. The energy of shock waves, number of shock waves per session, and number of sessions also influence the success rate. UDCA, 10 to 15 mg/kg of body weight per day, is administered orally to dissolve stone fragments, especially when residual stone fragments are larger than 2 mm in size, gallbladder function is poor, or the gallbladder has not cleared small fragments within 3 to 6 months of lithotripsy. An example of successful combined treatment is shown in Fig. 66.2 .

Efficacy

The percentages of patients who are free of stones after 6 and 12 months is 47% to 77% and 68% to 84%, respectively. Follow-up data reveal cumulative recurrence rates of 27%, 41%, and 54% at 3, 5, and 10 years, respectively. Recurrence is most often related to the presence of lithogenic bile and gallbladder dysmotility, rather than patient variables such as gender, age, and weight. Factors that predict higher rates of treatment failure include stone size larger than 16 mm, multiple stones, and stones with a CT density greater than 84 Hounsfield units. Recurrent stones are usually small and multiple and cause recurrent biliary pain. Maintenance therapy with UDCA after lithotripsy is not cost-effective and has not been shown to be effective.

Side effects of lithotripsy include petechiae of the skin at the site of shock-wave delivery (8%), hematuria (4%), and liver hematomas (<1%). No long-term liver biochemical abnormalities have been noted. Biliary pain develops in approximately one third of patients; cystic duct obstruction develops in 5%; and complications of stone passage, such as biliary pancreatitis, develop in less than 2%.

Lithotripsy is more cost-effective in older adults than in the young and less cost-effective in patients with multiple stones than in those with a single stone. When combined with UDCA, lithotripsy is at least as cost-effective as open cholecystectomy for patients with small stones and less cost-effective for those with large stones. When lithotripsy is compared with laparoscopic cholecystectomy, patients who undergo laparoscopic cholecystectomy experience a greater incremental improvement in quality of life at 6 months, whereas those who undergo lithotripsy have higher rates of recurrent stones and biliary symptoms.

Bile Duct Stones

Extracorporeal shock-wave lithotripsy has also been used in the management of choledocholithiasis. Intracorporeal electrohydraulic lithotripsy has been shown to be effective in this setting as well. These treatment options are reserved for patients who fail conventional endoscopic measures (see Chapter 70 ), mechanical lithotripsy, or surgical treatment of choledocholithiasis (see later). Appropriate indications for shock-wave lithotripsy are large stones impacted in the bile duct that are not amenable to endoscopic extraction, intrahepatic stones, stones above a biliary stricture, cystic duct remnant stones, and bile duct stones associated with Mirizzi syndrome (compression of the common hepatic duct) (see Chapter 65 ). Selection of patients for shock-wave treatment of bile duct stones is similar to that for treatment of uncomplicated gallbladder gallstones.

The success rate for treatment of bile duct stones is 70% to 90%. Most patients require endoscopic extraction of large stone fragments following treatment. Mild, transient hemobilia occurs in 10% of patients, and biliary sepsis develops in 4% following the procedure. Other complications are similar to those seen after lithotripsy for gallbladder stones. Because of the potential for septic complications, preprocedure endoscopic, nasobiliary, or percutaneous biliary drainage is performed. Antibiotics are given to minimize the risk of biliary sepsis.