Guidelines for the Treatment of Gallstones FREE

[The square-bracketed numbers are references to the numbered sections in the review article in this issue (Treatment of Gallstone Disease; see pages 606-619), which support statements made here.The Editors.]

Proper decision making for gallstone disease necessitates that clinicians and patients recognize three categories of disease. The first category encompasses silent gallstones (asymptomatic disease). The second category involves disease that causes uncomplicated biliary pain (symptomatic disease). A third category involves complications of gallstone disease, such as acute cholecystitis and gallbladder cancer. The present guideline focuses on the first two categories only.

This categorization of disease allows clinicians and patients to choose the treatment most appropriate to the specific patient. Therapy could be expectant management, a wait-and-see position in which intervention is postponed until a more serious problem develops. Therapy may be nonsurgical, in which only the gallstones, but not the gallbladder, are removed. The last option, the surgical approach, involves the removal of both the gallstones and the gallbladder. To choose the most appropriate option requires information about the efficacy, safety, and benefits of each.

Because expectant management delays treatment, this therapy poses a dilemma. Watchful waiting may avoid an unnecessary intervention. However, delaying an intervention is a tradeoff that could result in an adverse consequence by not preventing a future complication or by requiring the intervention when the patient is in an older, frailer state when the associated morbidity and mortality are greater [2.4].

Nonsurgical therapy dissolves gallstones by solubilizing their cholesterol through various methods. This therapy is generally limited to gallstones with a diameter less than 1.5 cm and whose content is primarily cholesterol. Options include oral bile acids that dissolve cholesterol stones by increasing the cholesterol in bile. However, suitable candidates would account for only 20% of cholecystectomy patients. Because bile acids must be taken daily for up to 2 years and because of their limited efficacy, their use is not widespread. A second option, methyl-tert-butyl-ether, is a contact solvent that dissolves cholesterol during repeated instillations into the gallbladder via a catheter. However, this therapy is still in the investigational stage. A third therapy, extracorporeal shock-wave lithotripsy, breaks stones into smaller pieces using acoustic shock waves. Then oral bile acid therapy dissolves these pieces. These options do bypass the risks and potential complications of surgery. Still, the clinician and patient should keep in mind that such nonsurgical therapies will neither prevent gallstone recurrence nor prevent gallbladder cancer [4.1.2].

Surgical removal of gallstones and gallbladder (cholecystectomy) prevents future pain, complications, gallstone recurrence, and gallbladder cancer. It spares the patient the length of nonsurgical therapies and is not limited by the size or composition of the gallstones. In return, cholecystectomy is accompanied by a higher risk for mortality, the associated risks of general anesthesia, postoperative morbidity, and a lengthy convalescence period (up to several months to return to full activity) [4.1, 4.1.1]. Laparoscopic cholecystectomy decreases the convalescent period, but it remains a new (1989) technology whose safety has not been fully assessed in large, comprehensive studies. Because of the absence of strict requirements for uniform, rigorous training, not all surgeons have been trained well enough to prevent bile duct injury or bowel perforation. Subsequently, the complication rate for bile duct injury may be substantially higher for the laparoscopic technique [4.1.1]. The laparoscopic technique has gained popularity among surgeons and the public alike. Until rigorous training becomes widespread, however, the clinician and patient should determine the experience of the surgeon before choosing the laparoscopic route.

By age 75, approximately 35% of women and 20% of men have developed gallstones. Although it is a common disease, most cases are asymptomatic and the patient remains unaware of its presence [2.1]. Symptomatic disease generally occurs as uncomplicated, infrequent biliary pain; episodes appear suddenly as severe, steady pain that is unaffected by household remedies, position change, or gas passage. If pain episodes do recur, the frequency may vary from weeks to years. Gallstone disease is not indicated by pain that is present uniformly, that frequently comes and goes, and that lasts less than 15 minutes. Belching, bloating, intolerance of fatty foods, and chronic pain are problems not attributable to gallstone disease. To the patient, however, the first episode of biliary pain can be upsetting if mistaken for a heart attack or abdominal catastrophe. Besides biliary colic, various complications are attributable to gallstone disease, including acute cholecystitis, acute pancreatitis, common duct obstruction, ascending cholangitis, gallbladder cancer, and gallstone ileus [2.2].

If the clinical history suggests gallstones, ultrasonography, oral cholecystography, or plain roentgenography can diagnose their presence. Asymptomatic gallstones are discovered incidentally [2.3].

Differentiation of symptoms proves important because the decision making for symptomatic gallstones differs from that for asymptomatic gallstones. Gallstone disease does not impose the long-term disabilities that accompany conditions such as congestive heart failure, stroke, and cancer. Therefore, the issue is not whether to alleviate a chronic or debilitating condition. Rather, the clinician and patient must decide whether to prevent (for example, by cholecystectomy) future biliary pain, a biliary complication, gallbladder cancer, or death.

Gallbladder cancer accounts for approximately one third to one half of gallstone-related deaths in the United States. The median age of persons with gallbladder cancer is 73 years. Even though 80% of patients with gallbladder cancer have gallstones, it has not been proved that gallstones are the cause. Alternately, a common underlying factor (for example, a property of bile) may cause both diseases, which could account for the association between their occurrence [4.2.1]. This alternative theory has clinically important implications. If cancer is related to bile and not to gallstones, then nonsurgical therapies (which leave the gallbladder intact) may not prevent gallbladder cancer. For asymptomatic gallstones, the potential effect of gallbladder cancer cannot be assessed easily because the incidence of gallbladder cancer is not well understood. Although the absolute risk for gallbladder cancer is low, gallbladder cancer is almost uniformly fatal, so even a low rate of cancer of 0.0002 per year would result in approximately a 0.4% risk for death during a period of 20 years [4.3.1.4].

For patients with symptomatic gallstones, gallbladder cancer has a greater effect on decision making. Cohort studies suggest that patients with symptomatic stones develop gallbladder cancer at higher rates than do patients with asymptomatic stones [4.3.2.4]. Cholecystectomy may be more advantageous to patients with symptomatic gallstones because it would remove the threat of gallbladder cancer.

In treating gallstone disease, the clinician and patient should first recognize that they can focus their decision making on two distinct goals: preventing future biliary pain or preventing a future biliary complication or death. Then the decision-making process should consider whether the disease is asymptomatic or symptomatic [5].

Because of a benign history and a low risk for ever incurring a major complication, expectant management should be recommended for patients with asymptomatic gallstones [4.2.1, 4.3, 4.3.1.1, 4.4, 4.6]. This recommendation applies to men and women of all ages. The effort and minor risks of surgical and nonsurgical intervention still outweigh their corresponding benefits. Expectant management must suffice until a perfectly safe, effective, convenient, and inexpensive treatment is developed.

Patients with a high risk for gallbladder cancer, for whom prophylactic cholecystectomy may be advisable, are exceptions to this recommendation [4.2.1, 4.3.1.1, 4.3.1.4, 4.6]. It remains uncertain, however, which patients with asymptomatic stones have an increased risk for gallbladder cancer. Patients with calcified gallbladders and New World Indians, such as the Pima Indians, do carry an increased risk for gallbladder cancer. This increased risk may also apply to patients with large (> 3 cm) stones [5].

For symptomatic gallstones, the choice of treatment proves more complicated. The following recommendations are suggested.

1. The clinician should determine if the biliary pain is the first episode and whether the pain indicates gallstone disease. From that assessment, the natural history can be roughly estimated using natural history data. (See Tables 4 and 5 in the corresponding background paper, pages 609 and 611) [4.2.2, 4.3.2.1, 5].

2. The clinician should assess the patient's treatment goals and attitudes. Specifically, the clinician should determine whether the patient wants to prevent another episode of pain. If so, treatment should be instituted [4.4, 5].

3. If the patient primarily wants to reduce the risk for death from gallstones and if the pain is a first episode, then the patient may choose to observe the pattern of pain before deciding about therapy. The clinician could advise that about 30% of patients with a pain episode may not incur more episodes even after prolonged follow-up [4.2.2, 4.3.2.1].

4. Symptomatic patients who opt for expectant management would have to believe that the gains from prophylactic cholecystectomy, in terms of life expectancy, do not warrant intervention. For such patients, the decision between immediate treatment or expectant management may be more a matter of personal choice and convenience [4.3.2.1, 4.3.2.2, 4.4, 5].

5. If the patient desires intervention, open cholecystectomy, or laparoscopic cholecystectomy if a skilled surgeon is available, is generally preferred [4.1.1, 4.3.1.2, 4.3.2.1, 4.3.2.2, 4.6].

6. The potential problem of bile duct injury should be considered, especially for laparoscopic cholecystectomy [4.1.1, 4.3.1.2]. If the patient is attracted to the reduced recovery time associated with the laparoscopic treatment, then the clinician should determine if the surgeon is appropriately qualified and experienced in this new technology.

7. Nonsurgical methods should be considered if the patient is a good candidate. Candidates for oral bile acids have small stones (diameter less than 0.5 cm) that float during oral cholecystography. The best candidates for lithotripsy have a solitary radiolucent stone smaller than 2 cm, with adjuvant oral bile acids. Methyl-tert-butyl-ether is still considered investigational [4.1.2, 4.3.1.3, 4.3.2.3].

8. Because gallstone disease treatment is usually not urgent, it may be reasonable to try nonsurgical therapy in certain patients. Such patients could have high mortality risks from surgery or may simply prefer a nonsurgical approach [4.3.2.3]. Still, these patients should be made aware that nonsurgical methods may not reduce the risk for gallbladder cancer.

Future gallstone research should focus on several areas, including the natural history of both asymptomatic and symptomatic gallstones, risks for developing gallbladder cancer, and issues concerning the safety of laparoscopic cholecystectomy compared with that of open cholecystectomy [6].