Gallstone disease

Epidemiology

• 10-15% of Americans in lifetime
• 80% will be asymptomatic

Risk factors

• Obesity
• Female
• 30-50yo
• Rapid weight loss (seen in 30% of patients after bariatric surgery, which can possibly be reduced by daily ursodeoxycholic acid)
• Pigment stones - haemoglobinopathies (sickle cell, hereditary spherocytosis, thalassaemia, CF, cirrhosis, Crohn's)

Pathophysiology

Cholesterol stones

• • Bile salts and lecithin render cholesterol soluble in bile by acting as detergents
  • When cholesterol concentration exceeds the solubility capacity of bile, it nucleates into solid cholesterol monohydrate crystals
  • Cholesterol precipitates into sludge, then stones as the precipitation progresses
  • Main factors provoking cholesterol gallstone formation:
    • Supersaturation of secreted bile from the liver
      • Either cholesterol and lipids for cholesterol stones, or haemoglobin processing products for pigment stones
    • Concentration of bile in the GB
      • Absorption of water and sodium
    • GB dysmotility
      • Allows more time for solutes to precipitate in the GB
      • Prolonged fasting, TPN, after vagotomy, somatostatin analogues
    • Accelerated crystal enucleation
      • Process accelerated by pro-nucleating agents - glycoproteins and immunoglobulins

Pigment stones

• • Complex mixtures of insoluble calcium salts of unconjugated bilirubin and inorganic calcium salts
  • High levels of unconjugated or conjugated bilirubin can predispose
  • Infection with certain organisms can favour stone formation - usually brown stones

Types of gallstones

• Cholesterol (>70%)
  • Mostly have calcium incorporated as well as cholesterol
• Pigment
  • Black - haemolytic conditions and cirrhosis. Occur with concentration of bilirubin, and fond almost exclusively in the GB. Contain bilirubin, calcium and mucin glycoproteins.
  • Brown - suggest disorder of biliary motility and associated bacterial infection - found in biliary tree
    • The brown colour comes from incorporation of cholesterol

Natural history

• Become symptomatic when they obstruct a visceral structure
• Small stones (<5mm) linked to biliary pancreatitis
• Large stones (>3cm) linked to acute cholecystitis and GB adenocarcinoma
• 20-30% of patients with asymptomatic stones will develop symptoms within 20 years
• 1% of patients with asymptomatic stones develop complications of their stones before onset of symptoms

Medical management of cholelithiasis

• High recurrence rates limit use to patients who cannot have a GA, have stones <1cm with minimal calcification, have mild disease only, have a patent cystic duct, and have good gallbladder mucosal concentration function
• Oral bile salt therapy (ursodeoxycholic acid)
  • Can take several years to work, especially with large gallstones
  • Dissolves gallstones by solubilising cholesterol from the surface
  • A patent cystic duct is required for it to enter the gallbladder
  • 10mg/kg/day in two to three divided doses, and up to 15mg/kg/day in patients with gallstones >2cm
  • Abdominal USS every 6-12 months - but keep in mind that stones dissolve from the inside out, so they do not seem to get smaller until the outer shell disintegrates all at once
  • Stones dissolve at about 1mm/month
  • Overall success rate is about 30-50% for stones <2cm, but symptoms seem to reduce within a few weeks of starting treatment
  • Recurrence 45% at five years
  • Continue UDA for at least six months after USS demonstrates clearance of stones, and can be continued indefinitely in patients who are high risk for recurrent stones and cholecystectomy
• Contact dissolution
• Extracorporeal shock wave lithotripsy
  • Recurrence rate 60% at five years - can be used in patients with single stones 0.5-2cm in size
  • 30-50% get biliary colic
  • Overall not useful
• Gallstone extraction
  • Can be done after percutaneous cholecystostomy
  • Dilate tract a few weeks after placement
  • Use a basket to extract stones and irrigate

Asymptomatic gallstones

• Cholecystectomy is not indicated except for certain specific populations
• Haemolytic anaemias
  • Sickle cell disease - extremely high rate of pigment stone formation, and cholecystitis can precipitate a crisis - reasonable to operate
  • Hereditary spherocystosis - once splenectomy is done, risk reverts to normal
• Spinal cord problems - non-op management unless symptomatic
• Higher risk of GB cancer - consider cholecystectomy
  • Calcified gallbladder wall (porcelain GB)
  • >2.5cm stones
  • Long common channel of bile and pancreatic ducts
• Diabetes and asymptomatic cholelithiasis is a weak relative indication for cholecystectomy, as there is a higher rate of gangrene

Biliary colic (symptomatic gallstones)

• Classically described as steady epigastric/RUQ pain lasting longer than 30 minutes, onset over about 5-10 minutes, lasting up to 6 hours
  • Visceral type pain
  • Can radiate to back
  • Can be a/w n/v
  • 50% of patients will report post-prandial pain
  • Pain longer than 24 hours is acute cholecystitis
  • Tenderness is likely to be an element of cholecystitis, as true biliary colic isn't associated with inflammation and therefore shouldn't produce tenderness
• Caused by temporary blockage of the cystic duct
• Differential diagnosis
  • Hepatic mets
  • Pyogenic liver abscess
  • Amoebic liver abscess
  • RHF
    • Pulsatile liver
    • Signs of RHF
    • Generally deranged LFTs
  • Hepatic adenoma/FNH
  • HCC
  • Hydatid cyst
  • Budd-Chiari syndrome
• Once stones are symptomatic, they are much higher risk for causing complications, so should have a cholecystectomy
  • 1-3% per year risk for mild symptoms
  • 7% per year for severe or recurrent symptoms

Acute cholecystitis

• Acute calculous cholecystitis
• Acalculous cholecystitis

Chronic cholecystitis

• Recurrent biliary colic or acute cholecystitis causing inflammation and scarring of the neck of the GB and cystic duct
• Lies along a continuum with biliary colic

GB polyps

• See separate section

GB wall calcifications

• Selective mucosal calcification
  • 6% risk of malignancy compared with 1% of matched cohort
  • Higher rate of malignancy than diffuse calcifications
• Diffuse intramural calcification (porcelain gallbladder)
  • Diffuse band of calcium infiltrating the muscular layer of GB wall
  • Chronic inflammation - 95% have gallstones
  • Small a/w cancer - maybe 1%

Choledocholithiasis

• CBD stones
• Pathophysiology
  • Can either arise de novo in CBD or pass down from GB
  • GB stones are cholesterol, CBD stones are brown pigment stones
  • Retained stones are secondary stones found in CBD within 2 years of cholecystectomy
• Presentation
  • Often silent
  • Dark urine, jaundice, pale stool
  • Generally painful when caused by stones - acute
• Diagnosis
  • CBD > 8mm
  • Obstructive LFTs
  • MRCP (se>90%, sp>99%)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
• Management:
  • CBDE or ERCP
  • >50% of those managed by just ERCP will have recurrent symptoms of biliary tract disease
  • Risk factors for failed ERCP:
    • Stones >2.5cm
    • Altered gastric or duodenal anatomy
    • Impacted stones
    • Intra-hepatic stones
    • Multiple stones
  • Prefer ERCP for rapid source control if there is evidence of cholangitis, suspected malignancy, or the CBD is <3mm

Gallstone ileus

• Secondary to bilioenteric fistula - most frequently GB to duodenum or small bowel. Cholecystocolic fistulae are rare.
  • Differentiate from Bouveret syndrome, in which the stone erodes into stomach and impacts at pylorus
• Impaction usually occurs in TI or ICV, and in most cases requires a stone >2.5cm
• Although it only causes 3% of SBO, more common in elderly females with virgin abdomen
• Clinical presentation
  • Typical SBO
  • Can see the 'tumbling stone' phenomenon, where pain changes location in the days leading up to presentation
• Radiographic
  • Rigler's triad
    • SBO
    • Pneumobilia
    • Aberrant stone in GIT
  • Need CT to clinch diagnosis, and see other stones within GIT
• Management
  • Operation required - laparotomy - can't evaluate bowel properly with laparoscopy
    • Manually palpate for stones
    • Enterotomy 5-30cm proximal to stone location in antimesenteric bowel (healthier bowel) and squish stone out. Close enterotomy transversely.
    • Whether to fix the fistula is controversial.
      • Only 10% or so will have recurrent symptoms, and only 10% of these will need an operation, so total risk of needing another operation is about 1%
      • Single-stage cholecystectomy and closure of cholecystoenteric fistula has morbidity up to 60%, compared with 25% for just enterolithotomy
      • Probably overall it's best to leave the biliary system alone at initial operation.
      • Consider single-stage procedure in patients with favourable anatomy and physiology
  • Delayed operation to fix fistula is unwarranted in asymptomatic patients

Gallstone pancreatitis

• See separate topic under 'pancreatitis'