Approach to the management of gallstones

INTRODUCTION — The presence of gallstones in the gallbladder (cholelithiasis) is common, particularly in Western populations. In the United States, gallstones are seen in approximately 6 percent of men and 9 percent of women [1]. Most individuals with gallstones are asymptomatic throughout their life and gallstones are found incidentally. The approach to the management of patients with gallstones depends upon the patient's symptoms, imaging test findings, and whether complications are present.

This topic will review the approach to the patient with uncomplicated gallstones. The discussion that follows is generally consistent with guidelines from the National Institute for Health and Care Excellence [2]. Separate topic reviews on gallstone disease and its complications include the following:

●(See "Gallstones: Epidemiology, risk factors and prevention".)

●(See "Overview of gallstone disease in adults".)

●(See "Acute calculous cholecystitis: Clinical features and diagnosis".)

●(See "Treatment of acute calculous cholecystitis".)

●(See "Acalculous cholecystitis: Clinical manifestations, diagnosis, and management".)

●(See "Choledocholithiasis: Clinical manifestations, diagnosis, and management".)

●(See "Acute cholangitis: Clinical manifestations, diagnosis, and management".)

●(See "Mirizzi syndrome".)

●(See "Gallstone ileus".)

●(See "Clinical manifestations and diagnosis of acute pancreatitis".)

TERMINOLOGY

●Gallstone disease – The term gallstone disease refers to gallstones that cause symptoms.

●Uncomplicated gallstone disease – The term uncomplicated gallstone disease refers to stones in the gallbladder that are associated with biliary colic in the absence of complications. (See "Overview of gallstone disease in adults", section on 'Complications'.)

●Complicated gallstone disease – The term "complicated gallstone disease" refers to gallstone complications (eg, acute cholecystitis, cholangitis, gallstone pancreatitis, gallstone ileus, and Mirizzi syndrome).

UNCOMPLICATED GALLSTONE DISEASE

Biliary colic

Acute pain management — During an acute attack of biliary colic, management is focused on pain control. Pain control can usually be achieved with nonsteroidal anti-inflammatory drugs (NSAIDs) [3]. We reserve opioids (eg, morphine, hydromorphone, meperidine) for patients who have contraindications to NSAIDs or who do not achieve adequate pain relief with NSAIDs.

We use ketorolac for patients who present to the emergency department with biliary colic. Treatment usually relieves symptoms within 10 to 30 minutes. Patients are then prescribed oral NSAIDs (eg, ibuprofen) for subsequent attacks that may occur while the patient is awaiting cholecystectomy. Patients who are managed as outpatients should be instructed to report to the emergency department if the pain does not resolve within four hours of the start of the pain because they are then at risk for developing complications such as acute cholecystitis. (See "Treatment of acute calculous cholecystitis", section on 'Pain control' and 'Elective cholecystectomy' below.)

The role of NSAIDs in the treatment of biliary colic was demonstrated in a meta-analysis of 11 randomized trials with 1076 patients that compared NSAIDs with no treatment, placebo, or other treatments [3]. The NSAIDs studied included ketorolac, diclofenac, tenoxicam, flurbiprofen, and ketoprofen. NSAIDs were more likely to control pain than placebo (relative risk [RR] 3.8; 95% confidence interval [CI] 1.7-8.6) or antispasmodics (RR 1.5; 95% CI 1.0-2.1). There was no difference in pain control between NSAIDs and opioids (RR 1.1; 95% CI 0.8-1.3). NSAIDs may also favorably alter the natural history of biliary colic, possibly due to the role of prostaglandins in the development of acute cholecystitis [4,5]. (See "Acute calculous cholecystitis: Clinical features and diagnosis", section on 'Epidemiology'.)

It was traditionally thought that meperidine is the narcotic of choice in patients with biliary colic or gallstone pancreatitis because it has less of an effect on sphincter of Oddi motility than morphine [6-8]. However, all opioids result in increased sphincter of Oddi pressure [7]. There are insufficient data to suggest that morphine should be avoided. Morphine has an advantage that it requires less frequent dosing than meperidine, which has a shorter half-life. (See "Treatment of acute calculous cholecystitis", section on 'Pain control'.)

Subsequent management

Elective cholecystectomy — For patients with typical biliary colic and gallstones on imaging who are surgical candidates, we recommend elective cholecystectomy in order to prevent future attacks of biliary colic and complications of gallstone disease (algorithm 1). For those patients whose biliary colic subsides while in the emergency department, follow-up for elective cholecystectomy should be arranged as emergency cholecystectomy is associated with a higher risk of complications [9].

We refer patients for cholecystectomy after an isolated attack of biliary colic even though approximately a third of patients with a first episode of biliary colic will not develop a recurrence within two years [10]. The rationale for our approach is that some patients may have unrecognized recurrent attacks if the initial attacks were not severe enough to have prompted medical attention.

Cholecystectomy is typically performed laparoscopically, though it may also be performed through an open right upper quadrant incision. Compared with open cholecystectomy, laparoscopic cholecystectomy reduces postoperative pain and significantly shortens hospital length of stay and convalescence, and time away from work, and is preferred by many patients from a cosmetic viewpoint. However, the laparoscopic procedure has been associated with an increased risk of common bile duct injury. In addition, the laparoscopic procedure may require conversion to an open procedure due to a variety of technical or patient issues. (See "Complications of laparoscopic cholecystectomy".)

Major complications of cholecystectomies include bleeding, abscess formation, bile leak, biliary injury, and bowel injury. Approximately 5 to 12 percent of patients develop diarrhea, mostly in response to a large load of ingested fat in the diet, though in many cases the diarrhea will improve or resolve over weeks to months. Cholecystectomy has also been associated with an increased risk for right-sided colon cancer, esophageal cancer, and small intestinal cancer. This may be related to the effects of increased concentrations of the bile acid deoxycholic acid in the gut lumen as a result of loss of the gallbladder, which normally acts as a reservoir for concentrated bile acids. (See "Approach to the adult with chronic diarrhea in resource-abundant settings", section on 'Post-cholecystectomy diarrhea' and "Epidemiology and risk factors for colorectal cancer", section on 'Cholecystectomy'.)

Alternatives to cholecystectomy — Patients who are unable to undergo cholecystectomy are managed expectantly. For patients who have had an isolated episode of biliary colic without complications and prefer to avoid surgery, expectant management may be a reasonable alternative. However, it is important that patients who elect not to undergo cholecystectomy understand the risk of subsequent complications and are educated about the symptoms of biliary colic and instructed to seek medical attention if symptoms develop (see "Overview of gallstone disease in adults", section on 'Natural history and disease course'). In addition, patients should undergo evaluation of stone type, size, and gallbladder function to determine if they are candidates for oral dissolution therapy. (See "Overview of gallstone disease in adults", section on 'Biliary colic' and "Overview of nonsurgical management of gallbladder stones", section on 'Management'.)

Asymptomatic gallstones

Expectant management — The majority of patients with asymptomatic (incidental) gallstones do not require treatment. Patients can usually be managed expectantly and referred for cholecystectomy if symptoms subsequently develop.

Prophylactic cholecystectomy is not indicated for most patients with asymptomatic gallstones since the risk of developing life-threatening, severe complications is low, and if symptoms do occur, they are generally mild initially. However, patients with asymptomatic gallstones must be educated about the symptoms of gallstone disease so they can seek treatment before more severe symptoms or complications develop. (See "Overview of gallstone disease in adults", section on 'Symptomatic gallstones' and "Overview of gallstone disease in adults", section on 'Complications'.)

There are no prospective trials comparing surgical or medical therapy for asymptomatic gallstones. However, decision analysis models have shown no benefit with prophylactic cholecystectomy. In fact, one decision analysis demonstrated that prophylactic cholecystectomy slightly decreased survival and was not associated with an appreciable gain in discounted life-years gained [11]. Although the model was constructed prior to the development of laparoscopic cholecystectomy, it is unlikely that the laparoscopic approach would significantly alter the results based upon the results of the sensitivity analysis included in the study.

Cholecystectomy in selected patients

●Increased risk of gallbladder cancer – Cholecystectomy is indicated for patients at increased risk for gallbladder cancer, provided they are good surgical candidates. (See "Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis".) (Related Pathway(s): Gallstones: Management of an adult with gallstones (symptomatic or asymptomatic).)

Patients at increased risk for gallbladder cancer include those with one of the following [12,13]:

•Anomalous pancreatic ductal drainage (in which the pancreatic duct drains into the common bile duct) (see "Biliary cysts", section on 'Abnormal pancreatobiliary junction and cancer').

•Gallbladder adenomas (see "Gallbladder polyps").

•Porcelain gallbladder (see "Porcelain gallbladder").

•Large gallstones (particularly if larger than 3 cm) [14].

●Hemolytic disorders – Patients with sickle cell disease and hereditary spherocytosis have a high incidence of forming pigment gallstones (50 percent or more) [15,16]. Because of this, we suggest cholecystectomy for patients with sickle cell disease if abdominal surgery is being performed for other reasons. In patients with hereditary spherocytosis, our approach is to perform a cholecystectomy if the patient has gallstones, and a splenectomy is being performed as part of the treatment for hereditary spherocytosis. (See "Hepatic manifestations of sickle cell disease", section on 'Cholelithiasis' and "Hereditary spherocytosis", section on 'Management'.)

Prophylactic cholecystectomy for asymptomatic gallstones is not indicated in patients with diabetes mellitus or those undergoing bypass surgery for obesity. Patients with diabetes mellitus may be at increased risk for the development of severe gangrenous cholecystitis [17]. However, the proportion of patients who develop biliary colic and other gallstone complications are similar to the general population [18-20]. Patients who have undergone gastric bypass surgery have a high incidence of developing gallstones (greater than 30 percent) [21,22]. However, cholecystectomy at the time of bypass in patients with asymptomatic gallstones is controversial. This is discussed in detail elsewhere. (See "Gallstones: Epidemiology, risk factors and prevention", section on 'Rapid weight loss' and "Bariatric operations: Late complications with subacute presentations", section on 'Cholelithiasis'.)

Atypical symptoms and gallstones

Evaluate for alternative etiologies — In some patients, the atypical symptoms are related to the gallstones, but that in others they are due to another cause and the gallstones are an incidental finding. Patients with atypical symptoms in the absence of biliary colic should undergo evaluation for alternative etiologies (algorithm 1). It is also important to note that symptoms may change over time and patients with continued symptoms should be carefully reassessed, paying specific attention to the type of ongoing symptoms and if biliary colic has developed [23].

Trial of ursodiol and subsequent management — In patients with no alternative explanation for atypical symptoms, we suggest an empiric trial of ursodiol for three months to identify patients who will benefit from cholecystectomy. Ursodiol relieves symptoms in many patients within a few weeks, even though gallstones are still present, possibly by changing the viscosity of bile. Dissolution of gallstones is slow and therapy may be required for two or more years. (See "Overview of nonsurgical management of gallbladder stones", section on 'Monitoring and duration'.)

Cholecystectomy is a reasonable alternative if a thorough evaluation for other causes of the patient's symptoms is negative and if the patient has a symptomatic response to dissolution therapy, especially in patients who want to discontinue ursodiol therapy. However, patients should be informed that the response rates to cholecystectomy in patients with atypical symptoms and gallstones are lower than those seen for patients with typical biliary colic. In a systematic review of 23 studies looking at the effect of cholecystectomy for patients with gallstones, 92 percent of patients with biliary colic had symptom relief following cholecystectomy [24]. However for patients with upper abdominal pain, symptom relief rates after elective cholecystectomy ranged from 66 to 77 percent. Factors that predict a response to cholecystectomy were evaluated in a study of 1008 patients with upper abdominal pain and gallstones [25]. Upper abdominal pain relief was reported by 594 patients (59 percent) following cholecystectomy. Independent factors associated with pain relief following cholecystectomy included pain that occurred once a month or less, pain that began one year or less prior to surgery, and nocturnal awakening due to pain. Factors associated with a lower likelihood of achieving pain relief were the presence of lower abdominal pain, an abnormal bowel pattern, and associated bloating. (See "Overview of nonsurgical management of gallbladder stones" and "Functional dyspepsia in adults", section on 'Management'.)

Patients who fail to respond to ursodiol should instead be treated for disorders more consistent with their symptoms (eg, functional dyspepsia in a patient with bloating). (See "Functional dyspepsia in adults", section on 'Management'.)

COMPLICATED GALLSTONE DISEASE — The complications of cholelithiasis include acute cholecystitis, choledocholithiasis, gallstone pancreatitis, acute cholangitis, gallstone ileus, Mirizzi syndrome, and gallbladder cancer. The management of these complications is discussed in detail elsewhere. (See "Treatment of acute calculous cholecystitis" and "Management of acute pancreatitis" and "Acute cholangitis: Clinical manifestations, diagnosis, and management" and "Gallstone ileus", section on 'Treatment' and "Mirizzi syndrome", section on 'Management' and "Surgical management of gallbladder cancer" and "Prognosis and adjuvant treatment for localized, resected gallbladder cancer" and "Treatment of advanced, unresectable gallbladder cancer" and "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on 'Initial diagnostic evaluation'.)

GALLSTONES IN PREGNANCY — The approach to women with gallstones who are pregnant is discussed in detail elsewhere. (See "Gallstone diseases in pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gallstones".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Gallstones (The Basics)" and "Patient education: Choosing surgery to treat gallstones (The Basics)")

●Beyond the Basics topics (see "Patient education: Gallstones (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Approach to management – Most individuals with gallstones are asymptomatic throughout their life and gallstones are found incidentally. The approach to the management of patients with gallstones depends upon the patient's symptoms, imaging test findings, and whether complications are present. Gallstone complications include acute cholecystitis, cholangitis, gallstone pancreatitis, gallstone ileus, and Mirizzi syndrome. In general, patients with sludge or microlithiasis are managed the same as patients with gallstones. The term uncomplicated gallstone disease refers to stones in the gallbladder that are associated with biliary colic in the absence of complications. (See 'Terminology' above.)

●Patients with biliary colic – For patients with typical biliary colic and gallstones on imaging, we recommend cholecystectomy rather than expectant management (Grade 1B). Such patients are likely to have recurrent attacks and are at risk for complications. For patients who have had an isolated episode of biliary colic without complications and wish to avoid surgery, expectant management may be a reasonable alternative provided that the patient understands the risk of subsequent complications developing. It is important that patients who do not undergo cholecystectomy be educated about the symptoms of biliary colic and be instructed to seek medical attention if symptoms develop. Dissolution therapy is a reasonable alternative in patients who are not surgical candidates. (See 'Biliary colic' above.)

●Asymptomatic patients with incidental gallstones – For patients with incidental gallstones, we recommend expectant management rather than performing prophylactic cholecystectomy (Grade 1C). Waiting until a patient becomes symptomatic before performing cholecystectomy prevents unnecessary surgery since the majority of patients with incidental gallstones will never develop biliary colic. However, prophylactic cholecystectomy is indicated for patients who are at increased risk for gallbladder cancer. It may also have a role in the treatment of some patients with hemolytic disorders. (See 'Expectant management' above and 'Cholecystectomy in selected patients' above.)

●Patients with atypical symptoms – For patients with atypical symptoms and gallstones, we suggest additional evaluation rather than cholecystectomy (Grade 2C). Such patients should be thoroughly evaluated for non-gallstone-related causes of their symptoms. Cholecystectomy is a reasonable alternative if a thorough evaluation for other causes of the patient's symptoms is negative and if the patient has a symptomatic response to dissolution therapy. (See 'Atypical symptoms and gallstones' above.)