J Am Board Fam Pract: first published as 10.3122/jabfm.8.1.22 on 1 January 1995. Downloaded from New Trends In The Treatment Of Calculus Disease Of The Biliary Tract Phillip Price, MD, and Thomas H. Hartranft, MD Background: New treatment methods for calculus disease of the biliary tract offer options that can benefit a variety of patients. Laparoscopic surgery, for example, has revolutionized biliary surgery and is now the preferred approach for the majority of patients. Methods: Using the key words "biliary tract," "calculus disease," and "cholecystectomy," MEDLINE files were searched from 1982 to the present. Articles dating before 1982 were accessed from the reference lists of the more recent articles. Results and Conclusions: This review describes the various procedures that could be effective options for patients with biliary stone disease, including an algorithm showing a proposed scheme for evaluating and treating this disease. Cholecystectomy - either laparoscopic or open - will likely remain the treatment of choice for most patients. The newer options, however, for treatment of both acute and chronic cholecystitis have proved effective in select cases. (J Am Board Fam Pract 1995; 8:22-8.) The treatment of patients with calculus disease of of interest has been directed toward the develop­ the biliary tract has changed dramatically during ment of new treatment methods. the past 20 years. Today a variety of new tech­ Approximately 80 percent of biliary tract niques offer effective and safe treatment for pa­ stones are composed of cholesterol. Many factors tients with biliary stone disease. Although sur­ predispose patients to the development of biliary gery will likely remain the best option for the calculi. Female sex, obesity, the use of oral con­ majority of patients, physicians and surgeons traceptives, multiparity, anticholesterol-lowering should be aware of the other options so they can drugs, and hypercholesterolemia have been carefully select the treatment that will best suit linked to the development of biliary calculi. In each patient's needs. addition, diseases of the terminal ileum - whether an inflammatory disease or a disease re­ Methods sulting in resection of that part of the intestine­ http://www.jabfm.org/ Using the key words "biliary tract," "calculus dis- can predispose a patient to the development of ease," and "cholecystectomy," MEDLlNE files cholesterol gallstones. were searched from 1982 to the present. Articles The development of the less common pig­ dating before 1982 were accessed from the refer­ mented gallstones has been linked to cirrhosis of ence lists of the more recent articles. the liver, congenital anomalies of the biliary tract, and hemolytic disease, possibly because of a pri­ on 30 September 2021 by guest. Protected copyright. Results mary hereditary deficit, such as spherocytosis, or Gallstones are a frequently occurring medical an acquired condition, such as replacement of a problem affecting approximately 10 percent of heart valve. men and 20 percent of women older than 55 Cholecystectomy is the reference standard for years of age in the United States. l It is estimated treatment of calculus disease of the biliary tract. that 20 million Americans currently have gall­ An estimated 500,000 cholecystectomies are per­ stones and that 1 million additional cases are di­ formed each year, making cholecystectomy the agnosed each year. Understandably, a great deal second most common abdominal operation, fol­ lowing Cesarean section. The procedure is safe and effective and is associated with a very low in­ Submitted, revised, 16 August 1994. cidence of morbidity and mortal~ty. The overall From the Department of Surgery, Mount Carmel Medical incidence of mortality ranges between 0.5 per­ Center, Columbus, Ohio. Address reprint requests to Thomas cent and 1.5 percent, and the morbidity ranges H. Hartranft, MD, Surgical Residency Program, Mount Carmel Medical Center, 793 W. State Street, Columbus, OH 43222. from 3.? percent to 6.9 percent. The incidence of 22 JABFP Jan.-Feb.1995 Vol. 8 No.1 J Am Board Fam Pract: first published as 10.3122/jabfm.8.1.22 on 1 January 1995. Downloaded from both morbidity and mortality has declined during Oral Dissolution with Bile Acids the past 25 years. Oral dissolution of biliary calculi is performed There are several published series with mor­ with chenodeoxycholic and ursodeoxycholic acids bidity rates of less than 3 percent. Gilliland and (ActigaU, Ciba-Geigy). First performed in 1937, Travers02 reported a series of 671 elective chole­ this technique gained popularity in the 1970s and cystectomies with a 0 percent mortality rate and a 1980s. There are several reports of results 3.9 percent morbidity rate. Ganey, et a1.3 reported achieved with chenodeoxycholic acid, most no­ a 0 percent mortality rate and a 3.9 percent mor­ tably, the National Cooperative Gallstone Study.4 bidity rate in a series of 1035 patients who under­ Both drugs are now available, with Actigall being went elective cholecystectomy. the most recent. Reports of the effectiveness of cholecystectomy Bile is composed mostly of water, along with vary widely. In cases in which the disease can be at­ conjugated bilirubin, organic and inorganic ions, tributed directly to the biliary tract - such as acute small amounts of protein, and three lipids (bile cholecystitis, gallstone pancreatitis, cholangitis, salts, cholesterol, and lecithin). \Vhen the per­ biliary colic, and gallstone ileus - surgery is very centage of bile acids and lecithin is adequate, cho­ effective. In patients with less specific symptoms, . lesterol will remain in solution. Bile acids keep such as dyspepsia, flatulence, bloating, fatty food in­ cholesterol in solution by forming a micelle. Cho­ tolerance, or nonlocalized pain, the efficacy could lesterol is kept in suspension by the bile salts and be much lower, probably because the surgery is the lecithin. \Vhen the amount of cholesterol in sometimes performed to alleviate symptoms unre­ bile exceeds the capacity of the micelle to keep it lated to the biliary tract. For example, a condition in solution, however, the cholesterol precipitates that has been described as post-cholecystectomy out, and there is a chance for the formation of syndrome probably does not exist and most likely cholesterol gallstones. occurs because the initial symptoms are related to At some point during the day the vast majority other gastrointestinal problems rather than prob­ of persons have bile that is supersaturated with lems directly associated with the biliary tract. Thus, cholesterol. Nevertheless, most persons do not proper patient screening and careful selection are form gallstones, suggesting that other factors, necessary to optimize the efficacy of this procedure. which are not completely understood, contribute The main advantages of cholecystectomy are to the formation of gallstones. These factors can that it is highly effective in not only relieving include (1) defective biliary secretion (vesicles symptoms but also halting the progression of cal­ with excess cholesterol, defective bile acid flow, http://www.jabfm.org/ culus biliary tract disease, as the calculi and the deficient bile flow); (2) a rapid nucleating factor primary site of their formation are removed. In that begins the precipitation of these cholesterol most cases cholecystectomy can be performed stones (calcium has been implicated); and (3) a with minimal risk to the patient, no long-term diseased gallbladder, either because of some ab­ follow-up treatment is required, and no long­ normality in the mucosa of the organ or because term adverse effects have been documented. The of poor contractility. on 30 September 2021 by guest. Protected copyright. primary disadvantage of this procedure is that it is The primary effect of bile acids is to decrease a major, intra-abdominal procedure requiring the amount of cholesterol that is secreted into the several weeks of recovery. bile. Ursodeoxycholic and chenodeoxycholic For any new treatment to become accepted, its acids both reduce the amount of cholesterol in efficacy and safety must be compared with those the bile by blocking the action of the HMG-co­ of the reference standard treatment, in this case, enzyme-A-reductase, which controls cholesterol cholecystectomy. The new treatments are usually formation. Also, it has been proposed that ur­ performed on carefully selected patients who are sodeoxycholic acid plays a role in stopping the otherwise healthy. Because the sickest patients transport of cholesterol from within the hepato­ (who will have the worst outcomes) will not be cytes to the bile. Once bile has micelles that are candidates for these new treatment methods, the not saturated with cholesterol, those micelles are results of cholecystectomy and those of the new able to act at the bile-stone interface, slowly re­ treatments must be compared carefully to avoid move small particles of cholesterol from the drawing incorrect conclusions. stone, and, during months to years, dissolve it Biliary Tract Calculi 23 J Am Board Fam Pract: first published as 10.3122/jabfm.8.1.22 on 1 January 1995. Downloaded from into small particles. Ursodeoxycholic acid has an­ Study in Canada reported a 10.9 percent dissolu­ other effect. There is a poorly understood liquid tion rate.8 It is now realized that suboptimal doses crystalline phase that causes removal of choles­ were administered (8 mglkg/d to 10 mglkg/d). At terol from stones to the bile, where it can he the optimal dose (15 mglkg/d for chenodeoxy­ removed. cholic acid and 8.5 mglkg/d for ursodeoxycholic Because these agents have slightly different ac­ acid), an overall dissolution rate of 15 percent to tions, it has been proposed that using them 20 percent could be achieved. together might have some type of synergistic These studies found a subgroup of patients effect. This view is held by German investigators, with a high (greater than 50 percent) chance of although it is not practiced routinely in the having their gallstones dissolved in 1 to 3 years.