65. Gallstone disease

1. Definition

• Cholelithiasis → stones in the gallbladder
• Choledocholithiasis → stones in the common bile duct (CBD)
• Biliary colic → pain from a stone blocking the gallbladder outlet for a short time, with no inflammation
• Symptomatic gallstone disease → colic or a complication: cholecystitis, CBD stones, cholangitis, pancreatitis, gallstone ileus

2. Epidemiology

• 10–15% of adults in the West; more with age (over 30% over 70)
• Women : men about 2–3 : 1
• Highest in Pima Indians and Chile; low in Africa and Asia
• Most (about 80%) never cause symptoms; risk of symptoms about 1–2% a year
• About 10–15% with gallbladder stones also have CBD stones
• Laparoscopic cholecystectomy → one of the commonest operations in general surgery

3. Aetiology and risk factors

Anatomy (revision)

• Gallbladder → fundus, body, neck, Hartmann's pouch; holds 30–50 mL
• Cystic duct → spiral valves of Heister; joins the common hepatic duct to form the CBD
• Calot's triangle (hepatocystic triangle) → cystic duct, common hepatic duct, inferior surface of the liver; contains the cystic artery (from the right hepatic artery) and Calot's lymph node
• Anatomical variants common → right hepatic artery in the triangle, short cystic duct, aberrant right hepatic ducts (bile leak)
• Bile → bile salts, phospholipid (lecithin), cholesterol; gallbladder concentrates bile 5–10 times

Risk factors ("fat, female, fertile, forty, fair" is a rough guide)

• Cholesterol stones:
  • Female sex, oestrogen (pregnancy, oral contraceptive, HRT)
  • Age over 40
  • Obesity, metabolic syndrome, diabetes
  • Rapid weight loss (bariatric surgery, very low calorie diets)
  • Family history, ethnic group
  • Drugs → octreotide, clofibrate, ceftriaxone
  • Ileal resection or Crohn's disease (loss of bile salts)
  • Long-term TPN, fasting (stasis)
• Black pigment stones → haemolysis (sickle cell, hereditary spherocytosis, thalassaemia), cirrhosis
• Brown pigment stones → bile duct infection and stasis (E. coli, parasites: Clonorchis, Ascaris); form in the ducts; East Asia

4. Pathogenesis

• Cholesterol stones → three factors:
  1. Supersaturation of bile with cholesterol (too little bile salt and lecithin)
  2. Nucleation → crystals form (mucin, proteins)
  3. Gallbladder stasis (poor emptying)
• Biliary sludge → first step; may pass or form stones
• Black pigment → unconjugated bilirubin and calcium bilirubinate; sterile; gallbladder
• Brown pigment → bacterial enzymes (beta-glucuronidase) deconjugate bilirubin; soft, earthy; in the ducts; primary duct stones
• Natural history:
  • Stone stuck in Hartmann's pouch or cystic duct → colic; stays stuck → cholecystitis
  • Stone passes into the CBD → obstructive jaundice, cholangitis, pancreatitis
  • Erodes into the bowel → gallstone ileus
  • Long-standing → gallbladder cancer (stones over 3 cm, porcelain gallbladder)

5. Classification

By composition

• Cholesterol (about 80% in the West) → pale yellow, large, often single or few; radiolucent
• Mixed → most common; cholesterol with pigment and calcium
• Black pigment → small, hard, many; 50% radio-opaque
• Brown pigment → soft; bile ducts
• Only about 10–15% of gallstones are radio-opaque on plain X-ray

By clinical state

• Asymptomatic (silent)
• Biliary colic
• Acute cholecystitis (calculous); chronic cholecystitis
• Mucocele (stone in the neck, sterile mucus) and empyema (pus)
• Choledocholithiasis, cholangitis, pancreatitis
• Mirizzi syndrome → stone in Hartmann's pouch or cystic duct compresses the common hepatic duct (Csendes types I–V: I compression, II–V fistula of increasing size)
• Gallstone ileus → stone passes through a cholecystoduodenal fistula; obstructs the terminal ileum
• Bouveret's syndrome → stone obstructs the duodenum or pylorus

6. Clinical picture

Symptoms

• Biliary colic:
  • Constant (not truly colicky) pain in the right upper quadrant or epigastrium, lasting over 30 minutes and under 6 hours
  • Often after fatty meals or at night
  • Radiates to the right scapula or shoulder
  • Nausea, vomiting
  • No fever, settles completely
• Vague "flatulent dyspepsia" (bloating, belching) → not reliably due to stones
• CBD stones → colic, jaundice, dark urine, pale stools, itch; may come and go (ball valve)
• Gallstone ileus → elderly woman; intermittent small bowel obstruction ("tumbling" stone)

Signs

• Colic → mild RUQ tenderness during attacks; Murphy's sign negative (no inflammation)
• Jaundice → yellow sclera; gallbladder usually not palpable (Courvoisier's law: a palpable gallbladder with jaundice is unlikely to be from stones, because a stone-filled gallbladder is fibrotic)
• Mucocele → large, smooth, non-tender gallbladder

7. Diagnosis

• Ultrasound → first test (sensitivity over 95% for gallbladder stones):
  • Echogenic foci with acoustic shadowing, move with position
  • Gallbladder wall, CBD diameter (normal under 6–7 mm; larger after cholecystectomy and in the elderly)
  • Less good for CBD stones (about 50%)
• Bloods → LFT (bilirubin, ALP, GGT, transaminases), FBC, CRP, amylase or lipase
• MRCP → CBD stones when LFT or ultrasound suggest them (sensitivity over 90%)
• Endoscopic ultrasound (EUS) → small CBD stones, microlithiasis; as accurate as MRCP
• ERCP → therapy, not diagnosis (pancreatitis risk)
• CT → complications (perforation, abscess, pancreatitis), gallstone ileus (Rigler's triad: small bowel obstruction, pneumobilia, ectopic stone)
• HIDA scan → acute cholecystitis (non-filling), biliary dyskinesia (ejection fraction under 35–40%)
• Intraoperative cholangiogram or laparoscopic ultrasound → CBD stones during surgery
• Risk of CBD stone (ASGE): high → stone seen in the CBD, cholangitis, bilirubin over 68 µmol/L with dilated CBD → straight to ERCP; intermediate → MRCP or EUS

8. Differential diagnosis

• Peptic ulcer, gastritis, functional dyspepsia
• Acute pancreatitis
• Myocardial infarction (inferior), pericarditis
• Right lower lobe pneumonia
• Hepatitis, liver abscess, Fitz-Hugh-Curtis syndrome
• Renal colic, pyelonephritis
• Irritable bowel syndrome, sphincter of Oddi dysfunction

9. Treatment

Conservative

• Asymptomatic gallstones → no surgery (expectant management); exceptions:
  • Porcelain gallbladder, stones over 3 cm, polyps over 10 mm (cancer risk)
  • Sickle cell disease, during other operations in selected cases, before transplant
  • Populations with high gallbladder cancer risk
• Biliary colic → analgesia (NSAIDs first, e.g. diclofenac; opioids), antiemetics; low-fat diet until surgery
• Ursodeoxycholic acid → dissolves small cholesterol stones in a functioning gallbladder; slow, recurrence 50% at 5 years; used after bariatric surgery to prevent stones
• ESWL (shock wave lithotripsy) → historical
• CBD stones:
  • ERCP with sphincterotomy and stone extraction (balloon or basket) → over 90% clearance
  • Large stones → mechanical lithotripsy, cholangioscopy with laser or electrohydraulic lithotripsy, large-balloon sphincteroplasty
  • Failed clearance → plastic stent for drainage, then retry or surgery
  • Unfit elderly → stent alone

Surgical

• Laparoscopic cholecystectomy → treatment of choice for symptomatic stones:
  1. Pneumoperitoneum; 4 ports (umbilical camera, epigastric, two right subcostal)
  2. Retract the fundus over the liver, Hartmann's pouch laterally
  3. Open the peritoneum over Calot's triangle
  4. Achieve the critical view of safety (Strasberg): Calot's triangle cleared of fat, lower third of the gallbladder off the liver bed, two and only two structures entering the gallbladder
  5. Clip and divide the cystic artery and cystic duct
  6. Dissect the gallbladder from the liver bed; remove in a bag
  7. Intraoperative cholangiogram → routine or selective (unclear anatomy, CBD stones suspected)
• Timing → elective; within 2 weeks for colic (NICE suggests soon after diagnosis to avoid readmission)
• Bail-out options when the critical view cannot be achieved → subtotal (fenestrating or reconstituting) cholecystectomy, fundus-first dissection, cholecystostomy, conversion to open
• Open cholecystectomy → Kocher subcostal incision; now for conversion, previous surgery, suspected cancer
• CBD stones found at surgery:
  • Laparoscopic CBD exploration (transcystic or choledochotomy with T-tube or primary closure) → one-stage, shorter stay
  • Or postoperative ERCP (two-stage); equal clearance
• Open CBD exploration → large stones, failed endoscopy; choledochoduodenostomy or hepaticojejunostomy for many primary duct stones
• Mirizzi → open or careful laparoscopic subtotal cholecystectomy; fistula → repair or hepaticojejunostomy
• Gallstone ileus → laparotomy, enterolithotomy (proximal to the stone), check for other stones; fistula repair later or never (elderly)
• After gallstone pancreatitis → cholecystectomy in the same admission (mild cases)

10. Complications

Of gallstones

• Acute cholecystitis, empyema, gangrene, perforation
• Obstructive jaundice, cholangitis, acute pancreatitis
• Mirizzi syndrome, cholecystoenteric fistula, gallstone ileus
• Gallbladder cancer

Of cholecystectomy

• Bile duct injury (0.3–0.5% laparoscopic; about twice the open rate) → most serious; Strasberg classification A–E
• Bile leak (cystic duct stump, ducts of Luschka) → ERCP and stent
• Bleeding (cystic or right hepatic artery, liver bed)
• Retained CBD stones, spilled stones (abscess)
• Bowel injury (port), port-site hernia
• Postcholecystectomy syndrome → persistent pain (retained stone, sphincter dysfunction, missed other cause)
• Diarrhoea (bile acids)
• ERCP → pancreatitis (3–5%), bleeding, perforation, cholangitis