Gallstones and cholecystitis

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

How common are gallstones? (Epidemiology)¹

• The prevalence of gallstones is approximately 10–15% of adults in Europe and the US.

• A review of cohort studies that explored the incidence of screen-detected gallstone disease in unselected general populations found that the incidence in European populations was 0.60–1.39% per year.

• Long-term follow-up in subgroups with screen-detected gallstone disease found that:

  • The cumulative incidence proportion of symptomatic disease was 18% over 20 years of follow-up.

  • Complicated gallstone disease was reported with low incidences of 8% or less depending on the length of follow-up.

  • Cholecystectomy rates varied across studies, but the highest cholecystectomy incidence was 25.8% over 10 years.

• In a study that reviewed the records of 40,819 people who had had a cholecystectomy in California in the 1990s, the spectrum of gallstone disease identified from the records included biliary colic (56%), acute cholecystitis (36%), acute pancreatitis (4%), choledocholithiasis (3%), gallbladder cancer (0.3%), and cholangitis (0.2%).

Risk factors

• Crohn's disease.

• Diabetes mellitus.

• Diets higher in triglycerides and refined carbohydrates, and low in fibre.

• Women have a 2–3 times higher incidence of gallstones compared to men.

• Increasing age; incidence rises significantly in people aged over 40 years.

• Positive family history.

• Non-alcoholic fatty liver disease.

• Haemolytic anaemia, cystic fibrosis, cirrhosis and ileal disease are associated with an increased risk of black pigment stones.

• Bacterial infection and partial biliary obstruction (eg, primary biliary cirrhosis or malignancy) are associated with an increased risk of brown pigment stones.

• Obesity; Body Mass Index (BMI) over 30.

• Prolonged fasting or weight loss exceeding 1.5 kg a week, including people who have had bariatric surgery.

• Use of hormone replacement therapy (HRT).

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.

• 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 (eg, 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.

Presentation in primary care

• Up to 80% of patients with gallstones are asymptomatic at the time of diagnosis. The number of patients with progression of asymptomatic to symptomatic disease is relatively low, ranging from 10-25%.²

• Gallstones may cause acute or chronic cholecystitis, biliary colic, pancreatitis or obstructive jaundice.

• 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.

Biliary colic

• The pain starts suddenly in the epigastrium or right upper quadrant (RUQ) and may radiate around to the back in the interscapular region.

• Contrary to its name, it often does not fluctuate but persists for longer than 30 minutes and up to 8 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 or gallbladder. Two or more of these conditions may overlap, so the diagnosis may not be easy. see also the article on Right upper quadrant pain.

Investigations

• Urinalysis, CXR and ECG may help exclude other diseases.

• Gallstones in the common bile duct may result in abnormal LFTs.

• Ultrasound Is the best way to demonstrate stones, being 90-95% sensitive:³

  • 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 LFTs, it is worth repeating the investigation after an interval. This may pick up stones which were previously missed.

• Consider referral for further investigation if results are normal but clinical suspicion remains high. This may include:

  • Magnetic resonance cholangiopancreatography (MRCP), if ultrasound has not detected common bile duct stones, but the bile duct is dilated and/or liver function test results are abnormal.

  • Endoscopic ultrasound (EUS) if MRCP does not allow a diagnosis to be made.

• Endoscopic retrograde cholangiopancreatography (ERCP) may be used for the diagnosis of CBD stones and has also evolved from a diagnostic to a therapeutic procedure for the removal of CBD stones.⁴

• Refer people for further investigations if conditions other than gallstone disease are suspected.

Cholecystitis⁵

Acute cholecystitis is an inflammation of the gallbladder. It usually occurs when a gallstone completely obstructs the gallbladder neck or cystic duct. Gallstones account for 90–95% of cases of acute cholecystitis. Obstruction of the gallbladder neck or cystic duct by a gallstone causes bile to become trapped in the gallbladder, resulting in irritation and increased pressure in the gallbladder.

Acalculous cholecystitis typically occurs in critically ill people due to bile stasis (due to gallbladder hypomotility/dysmotility) or bile thickening (due to dehydration). Conditions associated with biliary stasis or thickening include sepsis, extensive trauma, burns, major surgery, prolonged fasting or starvation, prolonged total parenteral nutrition, diabetes, end-stage renal disease, congestive heart failure and cardiovascular disease.

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 two 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.

Investigations

• FBC - the WCC is likely to be raised.

• Liver enzymes are often mildly abnormal.

• Ultrasound findings for cholecystitis:

  • Include a thickened GB wall (greater than 3 mm) and may also include pericholecystic fluid or air in the GB or the GB wall.

  • If the GB wall is thickened but there are no gallstones present then the diagnosis could still be acalculous cholecystitis.

• 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).

Management in primary care

If acute cholecystitis is suspected, admit the person to hospital for:

• Confirmation of the diagnosis, including abdominal ultrasound and blood tests (including white blood cell count, C-reactive protein, and serum amylase).

• Monitoring, including blood pressure, pulse, and urinary output.

• Treatment may include intravenous fluids, antibiotics, and analgesia.

• Surgical assessment for cholecystectomy.

Obstructive jaundice

See the separate Jaundice article.

Other presentations

Cholangitis

See the separate Cholangitis article.

Pancreatitis

See the separate Acute pancreatitis and Chronic pancreatitis articles.

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 than 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.⁶

Empyema

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

Gallstone ileus

Gallstone ileus is caused by occlusion of the intestinal lumen as a result of one or more gallstones. It is a rare complication of gallstones that occurs in 1-4% of all cases of bowel obstruction. The mortality is 12-27%.⁷

The management of gallstones, biliary colic and cholecystitis^{1 8}

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 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.⁹

• Chronic cholecystitis - the same principles apply to acute attacks of pain in patients with chronic cholecystitis.

Surgical

• Early cholecystectomy (to be carried out within one week of diagnosis) is recommended by the National Institute for Health and Care Excellence (NICE) for people with acute cholecystitis.⁸ A controlled cohort study found that such a target was feasible using a surgeon-led collaborative strategy.¹⁰

• 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.¹¹ An American study subsequently found that open cholecystectomy is associated with a higher mortality burden.¹²

• 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.¹³

• Percutaneous cholecystostomy (surgical drainage of the GB) is useful for patients who are unfit for cholecystectomy.

• Natural orifice transluminal endoscopic surgery (NOTES) has been developed. The peritoneal cavity is accessed via a natural orifice such as the mouth, rectum or vagina. Cholecystectomy via a gastroscope without laparoscopic guidance has been reported.¹⁴

Laser lithotripsy for difficult-to-treat bile duct stones
NICE has issued a technological appraisal guidance on the use of laser lithotripsy as an option for the management of difficult-to-treat bile duct stones.¹⁵ The procedure, usually carried out under general anaesthetic, involves the passage of an endoscope, inserted orally (or sometimes percutaneously), into the biliary tract. Once the tip of the fibre is in direct contact with the stone, a laser is focused on its surface to create a plasma bubble. This oscillates and induces cavitation with compressive waves to fragment the stone.

While NICE concludes that evidence on the efficacy of this procedure is adequate, evidence on its long-term safety is limited in quantity. They therefore recommend that the procedure should only be used with special arrangements for clinical governance, consent, and audit or research.

Risks of surgery

• 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.

• Fat intolerance may develop in a small proportion of patients - and a low-fat diet is recommended. However, evidence to support the usefulness of this diet is weak.¹⁶

• Post-cholecystectomy syndrome refers to heterogeneous group of symptoms and findings in patients who have undergone cholecystectomy. It's a rare situation; these patients can present with abdominal pain, jaundice or dyspeptic symptoms.¹⁷

The management of silent stones¹⁸

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

Consensus guidelines were commissioned by the British Society of Gastroenterology (BSG) in 2008 and updated in 2016.

The most recent guideline suggests:

• 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).

• Laparoscopic duct exploration and ERCP (supplemented by endoscopic papillary balloon dilatation (EPBD) with prior sphincterotomy, mechanical lithotripsy or cholangioscopy where necessary) should be considered in difficult cases. Percutaneous stone extraction and open surgery should be used as a last resort.

There appears to be a range of practice with respect to the use of endoscopic surgery in the management of CBD stones. A Cochrane review found that:¹⁹

• Open bile duct surgery seems superior to ERCP in achieving common bile duct stone clearance.

• There is no significant difference in the mortality and morbidity between laparoscopic bile duct clearance and the endoscopic options.

• There is no significant reduction in the number of retained stones and failure rates in the laparoscopy groups compared with the pre-operative and intra-operative ERCP groups.

• There is no significant difference in the mortality, morbidity, retained stones, and failure rates between the single-stage laparoscopic bile duct clearance and two-stage endoscopic management.

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.

• 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. One study suggested that conversion rates are proportional to the experience of the surgeon.²⁰

• 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.

Prevention