Oral dissolution therapy for cholelithiasis: mix and match. The authors conducted a prospective, randomized trial of chenodeoxycholic and ursodeoxycholic acid versus ursodeoxycholic acid alone in patients with cholelithiasis to determine their efficacy for dissolution of gallstones. One hundred and twenty patients with radiolucent gallstones, less than or equal to 15 mm and who had a functioning gallbladder were enrolled. The patients were divided into two groups based on the diameter of their largest stones. Seventy patients had stones larger than 5 mm but less than 15 mm, whereas 50 patients had stones that measured 5 mm or less. The patients were randomly assigned to treatment with chenodeoxycholic acid plus ursodeoxycholic acid (5 mm/kg of each) or ursodeoxycholic acid (10 mm/kg) alone. Oral cholecystography, plain abdominal x-rays, and ultrasonography of the gallbladder were done at 6, 12, and 24 months. Dissolution was deemed to be complete if not stones were visualized on two examinations. partial dissolution was defined as a 50% reduction in stone size and/or number. Stones that were not detected by cholecystography but still detected during ultrasonography were considered to be partially dissolved. Plasma triglycerides, serum cholesterol, HDL, and serologic liver function tests were determined at 1, 3, 6, 12, 18, and 24 months. In a select group of patients, bile-rich duodenal aspirates were aspirated and analyzed for biliary lipid contents. In the group with small stones, defined as less than or equal to 5 mm, complete stone dissolution occurred significantly more often utilizing combination therapy at 6 months (52% vs 24%), and this trend persisted, although no longer significant, at 12 and 24 months. Combination therapy also achieved an improved rate of dissolution for large stones within 6 months; however, this did not persist at 12 and 24 months. Although not statistically significant, stone calcification occurred less often with combined therapy. All treatment regimens were well tolerated, with only minor changes in bowel habits and mild elevations in serum transaminase levels. Serum lipid levels did not change with either therapy. The authors concluded that the combination of chenodeoxycholic acid and ursodeoxycholic acid was the preferred therapy for gallstone dissolution, because it dissolves stones more rapidly, with a lower incidence of stone calcifications, and thus might reduce the long-term cost of treatment. 