Gallstones and Cholecystitis

Gallstones may cause no symptoms and are occasionally discovered as an incidental finding when abdominal imaging is carried out for some other reason. 1-4% of asymptomatic patients in the adult Western world develop symptoms annually. The commonest 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. 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)

• Bile contains cholesterol, bile pigments (from broken-down haemoglobin) and phospholipids. If the concentrations of these vary, different kinds of stones may be formed.²
• Cholesterol stones (80% of all gallbladder (GB) stones in 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 species. Two thirds of gallstones are asymptomatic.³ Risk factors for stones becoming symptomatic are smoking and parity. Stones may cause acute or chronic cholecystitis, biliary colic, pancreatitis or obstructive jaundice.

Biliary colic is the commonest presentation, caused by a gallstone impacting in cystic duct or the ampulla of Vater. The second commonest presentation is acute cholecystitis, caused by distension of the gallbladder with subsequent necrosis and ischaemia of the mucosal wall.⁴ Obesity tends to increase the likelihood of developing symptoms.

The pain starts suddenly in the epigastrium or right upper quadrant 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 gallbladder 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 (eg stomach, pancreas, colon, GB). Two or more of these conditions may overlap, so the diagnosis may not be easy.

Investigations⁴

• 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 gallbladder and throw an acoustic shadow. Sometimes stones are not mobile, in which case they are not easy to discriminate 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 common bile duct and show the liver and hepatic bile ducts, but it can only identify with certainty about half of any stones in the common bile duct. 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, it is worth repeating the investigation after an interval. This may pick up stones which were previously missed.
• Fuller evaluation is needed if abnormal liver function tests or jaundice persist, in patients with acute pancreatitis, and when the common bile duct is noticeably dilated.
• Endoscopic retrograde cholangiopancreatography (ERCP) is currently the only reliable and widely available investigation for duct stones.
• CT may be useful when filling the bile duct is unsuccessful in endoscopic retrospective cholangiopancreatography or when the procedure cannot be used for other reasons.⁵
• 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).

Presentation

This follows impaction of a stone in the cystic duct, which may cause continuous epigastric or right upper quadrant pain, vomiting, fever, local peritonism, or a gallbladder 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 common bile duct (CBD) jaundice may occur.
• Murphy's sign: lay 2 fingers over the right upper quadrant. 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 gallbladder become thickened and scarred, and the gallbladder becomes shrivelled.

Investigations⁴

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

This occurs when a stone migrates from the gallbladder into the common bile duct or, less commonly, when fibrosis and impaction of a large stone in Hartmann's pouch compresses the common hepatic duct (Mirrizi'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.

Investigations³

• Liver function tests show a raised conjugated bilirubin concentration and alkaline phosphatase activity with normal or mildly raised aspartate transaminase activity.
• Ultrasonography confirms dilatation of the common bile duct (>7mm diameter) usually without distention of the gallbladder with common bile duct stones.
• ERCP is currently the only reliable and widely available investigation for duct stones, but is not without risk.
• Computerised tomography is a useful alternative when filling the bile duct is unsuccessful in endoscopic retrospective cholangiopancreatography or when the procedure cannot be used for other reasons.
• In the future, magnetic resonance cholangiography may replace ERCP for diagnostic purposes.⁶

Cholangitis

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

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.

Empyema

The obstructed gallbladder fills with pus. The patient may become quite toxic, and there is a marked fever and leucocytosis.⁶

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.

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 - these conditions 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.
• 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, post-operative complications, or operative time. However, hospital stay was shorter, and recovery time was quicker.⁸
• 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.
  Early surgery (within seven days of the onset of symptoms) appears to be safe and shortens hospital stay, but further studies are needed.⁹
• 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 gallbladder) 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.¹⁰
• 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 model, and this approach may well revolutionise the management of gallstones in the future.¹¹

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 stones

The preferred method is endoscopic sphincterotomy followed by laparoscopic cholecystectomy either at the same time or at a later stage.¹²

The management of other gallstone problems

• Cholangitis Medical treatment includes broad-spectrum intravenous antibiotics and correction of fluid/electrolyte disturbance. Surgical decompression of the gallbladder 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.¹³
• Empyema Intravenous antibiotics are combined with urgent decompression and removal of the gallbladder. Decompression may be carried out via a laparoscope under radiological guidance prior to gallbladder resection as this makes the gallbladder easier to handle. The conversion to open cholecystectomy is 40-80% but complications are no higher with laparoscopic removal than with open surgery.¹⁴
• 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.¹⁵

• 50% of patients will complain of digestive symptoms of some kind, so pre-operative counselling is important.¹⁶
• In 10% of patients, symptoms do not improve or actually worsen.⁶
• Some have retained, recurrent, or primary common bile duct stones and can be cured by their removal.
• A few may have biliary dyskinesia, which is improved by sphincterotomy.

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