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Approach to the management of gallstones
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● SUMMARY & RECOMMENDATIONS ❍ Large
● INTRODUCTION
● TERMINOLOGY
● UNCOMPLICATED GALLSTONE DISEASE ● Bookmark
❍ Biliary colic

■ Acute pain management

●
■ Subsequent management

■ Elective cholecystectomy

■ Alternatives to cholecystectomy

❍ Asymptomatic gallstones

■ Expectant management

■ Cholecystectomy in selected patients

❍ Atypical symptoms and gallstones

■ Evaluate for alternative etiologies

■ Trial of ursodiol and subsequent management

● COMPLICATED GALLSTONE DISEASE

● GALLSTONES IN PREGNANCY
● SOCIETY GUIDELINE LINKS
● INFORMATION FOR PATIENTS
● SUMMARY AND RECOMMENDATIONS
● REFERENCES

RAPHICS
●

Algorithms
❍ Management of gallstones

ELATED TOPICS
● Acalculous cholecystitis: Clinical manifestations, diagnosis, and management
● Acute calculous cholecystitis: Clinical features and diagnosis
● Acute cholangitis: Clinical manifestations, diagnosis, and management

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 Approach to the management of gallstones - UpToDate

● Adjuvant treatment for localized, resected gallbladder cancer

● Approach to the adult with chronic diarrhea in resource-rich settings
● Biliary cysts
● Choledocholithiasis: Clinical manifestations, diagnosis, and management
● Clinical manifestations and diagnosis of acute pancreatitis
● Colorectal cancer: Epidemiology, risk factors, and protective factors
● Complications of laparoscopic cholecystectomy
● Functional dyspepsia in adults
● Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis
● Gallbladder polyps and cholesterolosis
● Gallstone ileus
● Gallstones in pregnancy
● Gallstones: Epidemiology, risk factors and prevention
● Hepatic manifestations of sickle cell disease
● Hereditary spherocytosis
● Late complications of bariatric surgical operations
● Management of acute pancreatitis
● Mirizzi syndrome
● Overview of gallstone disease in adults
● Overview of nonsurgical management of gallbladder stones
● Patient education: Gallbladder removal (cholecystectomy) (The Basics)
● Patient education: Gallstones (Beyond the Basics)
● Patient education: Gallstones (The Basics)
● Porcelain gallbladder
● Society guideline links: Gallstones
● Surgical management of gallbladder cancer
● Treatment of acute calculous cholecystitis
● Treatment of advanced, unresectable gallbladder cancer

Approach to the management of gallstones

Authors:Salam F Zakko, MD, FACP, AGAFNezam H Afdhal, MD, FRCPISection Editor:Sanjiv
Chopra, MD, MACPDeputy Editor:Shilpa Grover, MD, MPH, AGAF
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2019. | This topic last updated: Sep 05, 2018.

INTRODUCTION
The presence of gallstones (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.

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 Approach to the management of gallstones - UpToDate

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 (30 to 60 mg adjusted for age and renal function given in a single
intravenous or intramuscular dose) for patients who present to the emergency
department with biliary colic. Treatment usually relieves symptoms within 10 to 30

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minutes. Patients are then prescribed oral NSAIDs (eg, ibuprofen 400 mg) 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

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Approach to the management of gallstones - UpToDate

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, 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-rich settings", section on 'Post-cholecystectomy diarrhea' and "Colorectal
cancer: Epidemiology, risk factors, and protective factors", 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 undergo cholecystectomy understand the risk of subsequent
complications. (See "Overview of gallstone disease in adults", section on 'Natural
history and disease course'.)

Patients should be educated about the symptoms of biliary colic and instructed to
seek medical attention if symptoms develop. 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.

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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".)

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 and cholesterolosis").

• 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 morbid 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]. Morbidly obese 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
"Late complications of bariatric surgical operations", section on 'Cholelithiasis' and
"Gallstones: Epidemiology, risk factors and prevention", section on 'Rapid weight
loss'.)

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

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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
"Adjuvant treatment for localized, resected gallbladder cancer" and "Treatment of
advanced, unresectable gallbladder cancer" and "Choledocholithiasis: Clinical
manifestations, diagnosis, and management", section on 'Diagnosis'.)

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GALLSTONES IN PREGNANCY
The approach to women with gallstones who are pregnant is discussed in detail
elsewhere. (See "Gallstones 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
5th to 6th 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 10th to 12th 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: Gallbladder removal (cholecystectomy) (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

● 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. In general, patients with sludge or
microlithiasis are managed the same as patients with gallstones. (See
'Introduction' above.)

● For patients with typical biliary colic and gallstones on imaging, we recommend

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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.)

● 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.)

● 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.)

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REFERENCES
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3. Colli A, Conte D, Valle SD, et al. Meta-analysis: nonsteroidal anti-inflammatory

drugs in biliary colic. Aliment Pharmacol Ther 2012; 35:1370.

4. Henderson SO, Swadron S, Newton E. Comparison of intravenous ketorolac

and meperidine in the treatment of biliary colic. J Emerg Med 2002; 23:237.

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diclofenac: a randomized, double-blind, placebo-controlled study.

Gastroenterology 1997; 113:225.

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7. Thompson DR. Narcotic analgesic effects on the sphincter of Oddi: a review of

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9. Dimou FM, Adhikari D, Mehta HB, Riall TS. Trends in Follow-Up of Patients
Presenting to the Emergency Department with Symptomatic Cholelithiasis. J
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10. Festi D, Sottili S, Colecchia A, et al. Clinical manifestations of gallstone disease:

evidence from the multicenter Italian study on cholelithiasis (MICOL).
Hepatology 1999; 30:839.

11. Ransohoff DF, Gracie WA, Wolfenson LB, Neuhauser D. Prophylactic

cholecystectomy or expectant management for silent gallstones. A decision
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12. Leitzmann MF, Rimm EB, Willett WC, et al. Recreational physical activity and
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13. Leitzmann MF, Giovannucci EL, Rimm EB, et al. The relation of physical activity
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