Gallstones may cause no symptoms and are occasionally discovered as an incidental finding when abdominal imaging is carried out for some other reason.

Epidemiology¹

1-4% of asymptomatic patients in the adult Western world develop symptoms annually. The most common presentations are biliary colic (56%) and acute cholecystitis (36%).¹ Other presentations and complications can occur (see below).
10-15% of people in the adult Western world develop gallstones. UK Hospital Episode Statistics' data for the years 2003-2005 showed that 25,743 patients were admitted as an emergency with acute gallbladder (GB) disease during that period.²

The adage 'fair, fat, fertile, female and forty' is only part of the story. Other risk factors include:

• Increasing age
• Positive family history
• Sudden weight loss, e.g. after obesity surgery
• Loss of bile salts, e.g. ileal resection, terminal ileitis
• Diabetes - as part of the metabolic syndrome
• Oral contraception - particularly in young women³

Interesting information came from a 10-year study of necropsy findings in South East England. Female gallstone subjects had a higher BMI than controls but males did not. Gallstones were twice as common in diabetics. There was no association.with heart disease. A third of elderly patients of both sexes had gallstones but most had not had surgery and gallstones were seldom a cause of death.⁴

Common bile duct (CBD) stones may occur in 3%-14.7% of all patients for whom cholecystectomy is performed.⁵

Types of stone

• Bile contains cholesterol, bile pigments (from broken-down haemoglobin) and phospholipids. If the concentrations of these vary, different kinds of stones may be formed.⁶
• Cholesterol stones (80% of all GB stones in the UK) are large, often solitary and radiolucent.
• Black pigment stones are small, friable, irregular and radiolucent.
  • Risk factors include haemolysis (e.g.sickle cell anaemia, hereditary spherocytosis, thalassaemia) and cirrhosis.
• Mixed stones are faceted and are comprised of calcium salts, pigment and cholesterol. 10% are radiopaque.
• Brown pigment stones (<5% in the UK) form as a result of stasis and infection within the biliary system, usually in the presence of Escherichia coli and Klebsiella spp. Two thirds of gallstones are asymptomatic.⁷ Risk factors for stones becoming symptomatic are smoking and parity. Stones may cause acute or chronic cholecystitis, biliary colic, pancreatitis or obstructive jaundice.

Presentation in primary care

Biliary colic is the most common presentation, caused by a gallstone impacting in the cystic duct or the ampulla of Vater. The second most common presentation is acute cholecystitis, caused by distension of the GB with subsequent necrosis and ischaemia of the mucosal wall.⁸ Obesity tends to increase the likelihood of developing symptoms.

Biliary colic⁷

The pain starts suddenly in the epigastrium or right upper quadrant (RUQ) and may radiate round to the back in the interscapular region. Contrary to its name, it often does not fluctuate but persists from 15 minutes up to 24 hours, subsiding spontaneously or with analgesics. Nausea or vomiting often accompanies the pain, which is visceral in origin and occurs as a result of distension of the GB due to an obstruction or to the passage of a stone through the cystic duct.

Differential diagnosis

Vague abdominal discomfort, distension, nausea, flatulence and intolerance of fats may also be caused by reflux, peptic ulcers, irritable bowel syndrome, relapsing pancreatitis and tumours, e.g. stomach, pancreas, colon, GB. Two or more of these conditions may overlap, so the diagnosis may not be easy.

Investigations⁸

• Urinalysis, chest X-ray and ECG may help exclude other diseases.
• Ultrasound is the best way to demonstrate stones. Definite gallstones are seen as sono-dense mobile areas within the GB and throw an acoustic shadow. Sometimes stones are not mobile, in which case they are not easy to differentiate from unimportant polyps and very small ones may be missed or fail to throw a helpful acoustic shadow. Ultrasonography can also allow measurement of the diameter of the CBD and show the liver and hepatic bile ducts but it can only identify with certainty about half of any stones in the CBD. If the ultrasound scan findings are negative but there is a high level of suspicion, such as in a patient with upper abdominal pain and abnormal liver function tests (LFTs), it is worth repeating the investigation after an interval. This may pick up stones which were previously missed.
• Fuller evaluation is needed if abnormal LFTs or jaundice persist, in patients with acute pancreatitis and when the CBD is noticeably dilated.
• Endoscopic retrograde cholangiopancreatography (ERCP) is currently the only reliable and widely available investigation for duct stones.
• Computerised tomography (CT) may be useful when filling the bile duct is unsuccessful in ERCP or when the procedure cannot be used for other reasons.⁹
• Oral cholecystograms (contrast given orally is concentrated in a healthy GB) and IV cholangiograms (IV contrast outlines the CBD) have largely been superseded by ultrasound but may have a place in selected cases (mainly elderly patients who are not going to be treated surgically).

Cholecystitis¹⁰

Risk factors

• Gallstones or biliary sludge (95% of patients)
• Hospitalisation for trauma or acute biliary illness (this represents the other 5%, without gallstones)
• Female gender
• Increasing age
• Obesity
• Rapid weight loss
• Pregnancy
• Crohn's disease
• Hyperlipidaemia

Presentation

This follows impaction of a stone in the cystic duct, which may cause continuous epigastric or RUQ pain, vomiting, fever, local peritonism, or a GB mass.

• The main difference from biliary colic is the inflammatory component (local peritonism, fever, raised white cell count (WCC)).
• If the stone moves to the CBD, jaundice may occur.
• Murphy's sign: lay 2 fingers over the RUQ. Ask the patient to breathe in. This causes pain and arrest of inspiration as the inflamed GB impinges on your fingers. The sign is only positive if a similar manoeuvre in the left upper quadrant does not cause pain.
• Repeated attacks of acute cholecystitis lead to chronic cholecystitis, in which the walls of the GB become thickened and scarred and the GB becomes shrivelled.

Investigations⁸

• Full blood count - the WCC is likely to be raised.
• Liver enzymes are often mildly abnormal.
• Ultrasound may show a thickened GB wall, pericholecystic fluid and stones.
• Hydroxyiminodiacetic acid (HIDA) cholescintigraphy may be used to reveal a blocked cystic duct.

This occurs when an obstructed CBD becomes contaminated with bacteria. In severe cases, symptoms can include pain in the RUQ, jaundice and high swinging fevers with rigors and chills (Charcot's triad).

Obstructive jaundice⁷

This occurs when a stone migrates from the GB into the CBD or, less commonly, when fibrosis and impaction of a large stone in Hartmann's pouch compresses the common hepatic duct (Mirizzi's syndrome). Conjugated bilirubin is water-soluble and is excreted in the urine, giving it a dark colour (bilirubinuria). At the same time, lack of bilirubin entering the gut results in pale, 'putty-coloured' stools and an absence of urobilinogen in the urine when measured by dipstick testing.

Investigations⁷

• LFTs show a raised conjugated bilirubin concentration and alkaline phosphatase activity with normal or mildly raised aspartate transaminase activity.
• Ultrasonography confirms dilatation of the CBD (>7 mm diameter) usually without distention of the GB with CBD stones.
• ERCP is currently the only reliable and widely available investigation for duct stones but is not without risk.
• CT is a useful alternative when filling the bile duct is unsuccessful in ERCP or when the procedure cannot be used for other reasons.
• In the future, magnetic resonance cholangiography may replace ERCP for diagnostic purposes.¹¹

Other presentations⁷

Cholangitis

See separate article Cholangitis

Pancreatitis

Passage of the gallstone into the bowel causes a temporary blockage of the biliopancreatic duct leading to a premature release of pancreatic enzymes. Symptoms include persistent epigastric pain radiating to the back which is relieved by leaning forwards and profuse vomiting. One study found that a serum total bilirubin level of or greater of 68.4 μmol/L on hospital Day 2 predicted persisting CBD stones with enough specificity to serve as a practical guideline for ERCP while minimising unnecessary procedures.¹²

Empyema

The obstructed GB fills with pus. The patient may become quite toxic and there is a marked fever and leucocytosis.¹¹

Gallstone ileus

A stone perforates the GB, ulcerating into the duodenum. It may pass on to obstruct the adjacent jejunum or terminal ileum. Subsequent inflammation may result in a fistula between these structures and the passage of a gallstone into the bowel.

• Investigations: abdominal radiography may show small bowel fluid levels indicative of obstruction of the small bowel, air in the biliary tree or a stone.

The management of gallstones, biliary colic and cholecystitis^1,10,13

Many patients can be managed initially at home. Factors to be taken into account include the age of the patient, social support and the severity of symptoms.

Non-surgical

• Biliary colic and acute cholecystitis are conditions which will usually respond to an opioid such as morphine or pethidine given parenterally and/or diclofenac by suppository. These routes will overcome difficulties in absorption caused by vomiting. Pain continuing for over 24 hours or accompanied by fever usually necessitates hospital admission. It is generally considered that patients who require antibiotics should have them intravenously in hospital. There is no evidence base to support the use of oral antibiotics at home, except where the patient has been discharged from hospital after a course of intravenous antibiotics but without having had surgical removal of the stones. One study also supported current guidelines that antibiotics before elective cholecystectomy were unnecessary.¹⁴
• Chronic cholecystitis The same principles apply to acute attacks of pain in patients with chronic cholecystitis.

Surgical¹

• Laparoscopic cholecystectomy is the preferred procedure. A Cochrane review found that there was no difference in mortality, postoperative complications, or operative time compared with open cholecystectomy. However, hospital stay was shorter and recovery time was quicker.¹⁵ A recent American study has subsequently found that open cholecystectomy is associated with a higher mortality burden.¹⁶
• Day case surgery has been shown by studies to be as safe and as acceptable to patients as 'overnight stay' surgery and is more cost-effective.¹⁷
• Early surgery (within seven days of the onset of symptoms) appears to be safe and shortens hospital stay.¹⁸ One study found that it could be delivered in UK hospitals, providing emergency theatre services were efficiently managed.¹⁹
• Postoperative complications are rare but do occur. The most significant is injury to the bile duct which occurs at a rate of 0.2% in both open and laparoscopic surgery.
• Percutaneous cholecystotomy (surgical drainage of the GB) is useful for patients who are unfit for cholecystectomy. One study of 55 patients found a successful biliary drainage rate of 98%, and 95% of patients recovered well and left hospital.²⁰
• Natural orifice transluminal endoscopic surgery is currently being developed. The peritoneal cavity is accessed via a natural orifice such as the mouth, rectum or vagina. A successful cholecystectomy has been carried out on a porcine model²¹ and a human vaginal cholecystectomy has been reported.²² This approach may well revolutionise the management of gallstones in the future.

The management of silent stones¹

Patients should be managed on a case-by-case basis. 1-4% of asymptomatic patients develop problems related to gallstones annually, so the odds are in favour of a 'watch and wait' policy. Younger patients tend to develop complications more frequently because they have a longer time for the gallstones to cause problems and smaller stones cause more problems than larger ones, as they are more likely to become dislodged.

The management of bile duct stones²³

Consensus guidelines were commissioned by the British Society of Gastroenterology in 2008.

These suggest:

• Cholecystectomy and exploration of the CBD if the GB is present, preferably through a laparoscope
• Biliary sphincterotomy and endoscopic stone extraction if the GB has been previously removed
• Consider a biliary stent if stones are irretrievable (may be definitive treatment if the patient is unfit for surgery)
• Consider advanced endoscopic percutaneous techniques (e.g. mechanical lithotripsy or extra-corporeal shock-wave lithotripsy

The preferred method is endoscopic sphincterotomy followed by laparoscopic cholecystectomy, either at the same time or at a later stage.²⁴

The management of other gallstone problems

• Cholangitis: medical treatment includes broad-spectrum intravenous antibiotics and correction of fluid/electrolyte disturbance. Surgical decompression of the GB may be required. Endoscopic drainage has replaced emergency surgical common duct exploration and T-tube drainage in patients with severe cholangitis. Percutaneous transhepatic biliary drainage (PTBD) is another option.²⁵
• Empyema: intravenous antibiotics are combined with urgent decompression and removal of the GB. Decompression may be carried out via a laparoscope under radiological guidance prior to GB resection as this makes the GB easier to handle. The conversion to open cholecystectomy is 40-80% but complications are no higher with laparoscopic removal than with open surgery.²⁶ One study suggested that conversion rates are proportional to the experience of the surgeon.²⁷
• Gallstone ileus: treatment is traditionally by laparotomy and 'milking' the obstructing stone into the colon or by enterotomy and extraction. Recently, laparoscopic techniques have been used.²⁸

Long-term issues for GPs

• 50% of patients will complain of digestive symptoms of some kind, so preoperative counselling is important.²⁹
• In 10% of patients, symptoms do not improve or actually worsen.¹¹
• Some have retained, recurrent, or primary CBD stones and can be cured by their removal.
• A few may have biliary dyskinesia, which is improved by sphincterotomy.

Prevention

Ursodeoxycholic acid is useful in preventing high-risk patients (e.g. morbidly obese patients undergoing rapid weight loss following barometric surgery) from developing gallstones. However, studies suggest that ursodeoxycholic acid has no effect on the reduction of biliary symptoms, once the stones have formed.¹

Document references

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Acknowledgements