Oral Dissolution Research Articles

Interventional Radiologic Alternatives to Cholecystectomy

It has been estimated that 20 million people in the United States have gallstone disease. The choice of the optimal management strategy for a patient with symptomatic gallstones in the 1990s will take into account the clinical status of the patient, the characteristics of the gallstones, and the patient's preference. Only patients whose doctors understand the advantages and disadvantages of the newer methods can make properly informed choices. When interventional radiologic alternatives to cholecystectomy are being contemplated, one approach is to first consider the patient's clinical presentation (acute or nonacute) and then their risk of death after cholecystectomy (low or high). Figure 5 shows an algorithmic approach to the management of gallbladder stones based on this concept. This algorithm also can be used as a framework for discussion of treatment options with any individual patient.

Non-surgical options for the management of gallstone disease: an overview

The modalities for the non-surgical treatment of gallstones include oral dissolution by bile salts, local dissolution by methyl-tert-butyl-ether (MTBE), extracorporeal shockwave lithotripsy (ESWL) and percutaneous gallstone clearance. The results of oral bile salt therapy for cholesterol stones have been disappointing, and the only indication for this treatment is after ESWL. The high efficacy initially reported for MTBE has not been confirmed by subsequent experience in other centres: this therapy is toxic and best confined to specialized centres. ESWL, though effective in noncalcified stones, has limited overall applicability (approx. 15%) and is frequently followed by recurrence despite maintenance therapy with oral bile salts. Percutaneous gallstone clearance (radiologic or laparoscopic) has been superseded by laparoscopic cholecystectomy. This offers definitive treatment in a single session and has significant advantages over open cholecystectomy in terms of short hospital stay and accelerated recovery with early return to work or full activity. Destruction of the gallbladder by sclerosant agents (chemical cholecystectomy) requires further experimental evaluation before its introduction to clinical practice.

Oral Dissolution Treatment of Gallstones with Bile Acids

Oral Dissolution Treatment of Gallstones with Bile Acids

Medical management of gallstones

Ursodeoxycholic acid (ursodiol) is an oral dissolution agent recently approved by the Food and Drug Administration for treatment of cholelithiasis. The authors conducted a cost-effectiveness analysis comparing ursodiol with elective cholecystectomy and expectant management for men and women of ages 50 and 70 with typical chronic biliary symptoms. Using published literature and national cost data, the authors performed a decision analysis in which the outcome measures were life expectancy, quality-adjusted life expectancy, and expected lifetime treatment cost. The analysis applies to patients with symptoms of biliary colic, noncalcified gallstones less than 20 mm in diameter, and functioning oral cholecystograms, who are candidates for elective cholecystectomy. Excluded were patients with acute cholecystitis or known or suspected common bile duct stones. Ursodiol is both clinically advantageous and less expensive than surgery for symptomatic men aged 64 or more, and for symptomatic women aged 69 or more. At ages younger than these, the clinical advantage of surgery is small and could be nullified if ursodiol were targeted at patients for whom dissolution is most likely to be effective, based on evidence of stone size and composition. Expected lifetime costs of ursodiol range from $300-400 more than surgery for 50-year-olds to $700-1,000 less than surgery for 70-year-olds. Ursodiol is the preferred choice for patients throughout this age range who are at significantly elevated risk of operative mortality. Ursodiol is a clinically advantageous and cost-effective alternative to elective cholecystectomy, especially for older and high-risk patients.

Nonsurgical Management of Cholelithiasis

Cholecystectomy is accepted and effective therapy for symptomatic cholelithiasis; until recently, it was the only therapeutic option for patients with gallstones. Recently available alternative therapy for cholelithiasis includes oral dissolution therapy with the bile salts ursodeoxycholic acid and chenodeoxycholic acid, extracorporeal shock wave lithotripsy, and instillation of methyl tert-butyl ether directly into the gallbladder. The role of each of these methods in the treatment of patients with gallstones will be reviewed, as well as the epidemiology, pathogenesis, natural history, and roentgenographic characteristics of gallstones, all of which are relevant when choosing appropriate therapy for the individual patient.

Gallstone dissolution therapy with ursodiol. Patient selection.

Ursodeoxycholic acid (ursodiol) has been shown to be an effective oral agent for dissolution of gallstones that also has a favorable safety profile. In the selection of patients as candidates for this treatment, stone characteristics and the functional status of the gallbladder are the two most important criteria. Small, primarily cholesterol stones (radiolucent on plain film) are the most suitable for oral dissolution therapy. In addition, a functioning gallbladder (as evidenced by visualization on oral cholecystogram) is required to concentrate the ursodiol-enriched bile and effect stone dissolution. Ursodiol should not be used during pregnancy, in women likely to become pregnant, or in severe acute or chronic intrahepatic cholestasis. Acute cholestasis and common bile duct obstruction also preclude this treatment. Screening tests include basic laboratory tests of liver function, sonographic evaluation of the gallbladder and biliary tree, plain film of the abdomen, and oral cholecystogram. Since few patients meet all the selection criteria ideally, the decision to undertake treatment with ursodiol must be based on the entire clinical profile and on the patient's willingness to accept the predicted likelihood of success.

Percutaneous endoscopic cholecystolithotripsy. Work in progress.

In spite of long-term adjunctive oral dissolution therapy, residual gallstones have been reported in up to 50% of gallstone patients 3 months after extracorporeal shock-wave lithotripsy. Six women and five men, aged 31-75 years, underwent percutaneous endoscopic cholecystolithotripsy between April 1988 and October 1988. The gallbladder was punctured by means of an anterior transperitoneal approach. The tract was dilated, and gallstones were removed with a modified 21-F cholecystoscope under direct visual inspection. Calculi too large for extraction were disintegrated with ultrasound or electrohydraulic lithotripsy. Eight patients were stone-free and two had small residual stones 3 months later; nine were stone-free 6 months after the procedure. Although more invasive than shock-wave lithotripsy, percutaneous endoscopic cholecystolithotripsy has the advantage of immediate removal of more calculi, causes less pain, necessitates less postoperative immobilization, and allows patients to leave the hospital sooner.

Trends in the treatment of gallstone disease: Putting the options into context

The new nonsurgical methods of treating gallstone disease rely on fragmentation, such as with extracorporeal shock-wave lithotripsy (ESWL), or dissolution, such as with ursodiol. Fragmentation alone is usually insufficient for gallbladder stones, and dissolution is only possible for cholesterol stones. Although oral dissolution with or without ESWL is an attractive alternative to surgery, only 25 percent of patients are candidates for this therapy. Dissolution of gallbladder stones by topical application of methyl tert-butyl ether (MTBE) is another option whose safety is still open to question. Therefore, cholecystectomy will remain the principal treatment for symptomatic gallbladder stones. Common duct stones can be eliminated in 90 percent of cases by endoscopic sphincterotomy alone, and fragmentation of large common duct stones by mechanical endoscopic lithotripsy or ESWL can bring the success rate up to about 95 percent. Unless cholecystectomy is also required, surgery will have a secondary role in the treatment of common duct stones.

Review article: dissolution of gallstones in the biliary tree

There are a variety of methods for dissolving gallstones in the biliary tree, which include oral therapy and direct contact dissolution. Cholesterol gallstones are most amenable to dissolution. Developments in non-operative physical methods to remove gallstones (particularly endoscopic papillotomy and extracorporeal shock-wave lithotripsy have diminished the use of chemical dissolution. However, in selected patients, there remains a place for chemical dissolution, but often in conjunction with the physical techniques.

Analytic Reviews : Nonsurgical Alternatives in the Management of Gallstones

Until recently, the only therapeutic option for patients with symptomatic gallstones was surgery. However, sev eral new and innovative nonsurgical approaches are cur rently available, including oral dissolution therapy with the bile salts, ursodeoxycholic and chenodeoxycholic acids, instillation of liquid solvents such as methyl tert- butyl ether directly into the gallbladder or the common bile duct, and extracorporeal shock-wave lithotripsy. We review the role of each of these methods in the management of patients with gallstones as well as the epidemiology, pathogenesis, natural history, and radi ological characteristics of gallstones, all important con siderations when choosing appropriate treatment for the individual patient.

経口すい石溶解療法に関する研究 慢性すいろう犬における血中およびすい液中ｄｉｍｅｔｈａｄｉｏｎｅの動態

経口すい石溶解療法に関する研究 慢性すいろう犬における血中およびすい液中ｄｉｍｅｔｈａｄｉｏｎｅの動態

Stones in the common bile duct: experience with medical dissolution therapy.

Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist.