Gallstone (cholelithiasis) is a common disease in this country and is associated with significant morbidity. Open and laparoscopic cholecystectomy remains the mainstay in the methods of treating patients with symptomatic disease. For selected patients, non-invasive treatment such as Actigall (ursodiol) therapy may be appropriate. Contact dissolution by means of ethyl propionate (EP), isopropyl acetate (IA), or methyl tertiary butyl ether (MTBE), has also been used in high-risk patients such as the elderly, patients who are too ill to undergo surgery, and individuals with idiosyncratic reactions to anesthesia.

In contact dissolution of gallstones, the solvent is usually introduced through a percutaneous trans-hepatic catheter into the gallbladder. A catheter is inserted through a small needle puncture into the gallbladder under fluoroscopic or ultrasonographic guidance. The catheter is then connected to a computerized peristaltic pump that delivers small amounts of solvent continuously to slowly dissolve the stones and removes any remaining stone fragments. Gallstones can usually be cleared in hours to days. Care must be taken to limit the time of contact between instillation and drainage to avoid discharge of this potentially toxic agent into the bile duct or the duodenum. Failure to do so may result in transient abdominal pain and duodenitis.

There is a significant risk of complications with contact dissolution of gallstones. As one commentator noted, "none [of the several contact solvents available] is a simple, safe, and effective method of treating gallstones" (Lee, 1999). Complications of use of contact solvents include those caused by the percutaneous puncture procedure and side effects if the solvent drains into the duodenum (e.g., hemolytic anemia, erosive or hemorrhagic duodenitis, aspiration pneumonia, and somnolence).

Although there is preliminary evidence that contact dissolution is effective in treating cholesterol gallstones, this is considered an investigational procedure. None of the agents used (EP, IA, and MTBE) has been approved by the Food and Drug Adminsitration for the treatment of gallstones. As one authority commented regarding direct contact dissolution of gallstones, "this investigational therapy has not gained sufficient acceptance" and, with the introduction of laparoscopic cholecystectomy, contact dissolution has been "practically abandoned" (Paumgartner, 1998). In a review on cholesterol gallstone disease, Portincasa et al (2006) stated that the "contact" method for stone dissolution by MTBE via percutaneous puncture of the gallbladder or extracorporeal shockwave lithotripsy have been abandoned.

An UpToDate review on “Dissolution therapy for the treatment of gallstones” (Nunes, 2015) states that “Contact dissolution – Contact dissolution of gallstones with solvents instilled directly into the gallbladder was another approach to treating gallstones without surgery that is no longer performed. While results with this technique were good, with up to 92 % of patients with radiolucent stones achieving complete stone dissolution, the procedure was technically complex, had potentially significant side effects, and was associated with high rates of stone recurrence. In addition, the most widely used solvent, methyl tert-butyl ether (MTBE), is no longer available due to concerns regarding toxicity”.

Scope of Policy

This Clinical Policy Bulletin addresses contact dissolution for gallstones.

Experimental and Investigational

Aetna considers contact dissolution (also known as direct solvent dissolution or litholysis) experimental and investigational for the treatment of gallstones because none of the agents used for contact dissolution – ethyl propionate, isopropyl acetate, methyl tertiary butyl ether – has been approved by the U.S. Food and Drug Administration for this indication and the safety and effectiveness of this approach has not been established.