GASTROENTEROLOGY
BILIARY TRACT DISEASE
CHOLELITHIASIS (GALLSTONES)
Epidemiology & pathogenesis (J Hep 2008;48:S124)
• >10% adults in the U.S. have gallstones; a/w ↑ overall mortality (Gastro 2011;140:508)
• Bile = bile salts, phospholipids, cholesterol; ↑ cholesterol saturation in bile + accelerated nucleation + gallbladder hypomotility → gallstones
• Risk factors: 
; South, Central, Native American; ↑ age (>40 y), obesity, pregnancy, TPN, rapid ↓ wt; drugs (OCPs, estrogen, clofibrate, octreotide, ceftriaxone); ileal disease
• ? statin use >1 y ↓ risk of sx gallstones & cholecystectomy (JAMA 2009;302:2001)
Types of gallstones
• Cholesterol (90%): 2 subtypes
mixed: contain >50% cholesterol; typically smaller, multiple stones
pure: 100% cholesterol; larger, yellow, white appearance
• Pigment (10%)
Black: unconjugated bilirubin (chronic hemolysis, cirrhosis) and calcium
Brown: stasis & infection in bile ducts → bacteria deconjugate bilirubin → precipitates w/ calcium; seen w/ duodenal diverticula, biliary strictures, parasites
Clinical manifestations
• May be asx; biliary pain in ~2%/y; once sx, rate of complications ~2%/y
• Biliary pain (“colic”) = episodic RUQ or epigastric abd pain that begins abruptly, is continuous, resolves slowly and lasts for 30 min–3 h; ± radiation to scapula; nausea
• May be precipitated by fatty foods
• Physical exam: afebrile, ± RUQ tenderness or epigastric pain
Diagnostic studies
• RUQ U/S: Se & Sp >95% for stones >5 mm; can show complications (cholecystitis); should be performed only after fasting ≥8 h to ensure distended, bile-filled gallbladder
Treatment
• Cholecystectomy (CCY), usually laparoscopic, if symptomatic
• CCY in asx Pts w/: GB calcification (~7% risk of ca) (Surgery 2001;129:699), GB polyps >10 mm, Native American, stones >3 cm or bariatric surgery or cardiac transplant candidates
• Ursodeoxycholic acid (rare) for cholesterol stones w/ uncomplicated biliary pain or if poor surgical candidate; also reduces risk of gallstone formation with rapid wt loss
• Biliary pain: NSAIDs (eg, diclofenac 50 mg IM) drug of choice, efficacy 
opiates & ↓ complications (Aliment Pharmacol Ther 2012;35:1370)
Complications
• Cholecystitis: 20% of sx biliary pain → cholecystitis w/in 2 y
• Choledocholithiasis → cholangitis or gallstone pancreatitis
• Mirizzi’s syndrome: common hepatic duct compression by cystic duct stone → jaundice, biliary obstruction
• Cholecystenteric fistula: stone erodes through gallbladder into bowel
• Gallstone ileus: SBO (usually at term ileum) due to stone in intestine that passed thru fistula
• Gallbladder carcinoma (~1% in U.S.)
CHOLECYSTITIS (NEJM 2008;358:2804)
Pathogenesis
• Acute cholecystitis: stone impaction in cystic duct → inflammation behind obstruction → GB swelling ± secondary infection (50%) of biliary fluid
• Acalculous cholecystitis: gallbladder stasis and ischemia → inflammatory response; occurs mainly in critically ill, hosp. Pts (postop major surgery, TPN, sepsis, trauma, burns, opiates, immunosuppression, infxn [eg, CMV, Crypto, Campylobacter, typhoid fever])
Clinical manifestations
• History: RUQ/epigastric pain ± radiation to R shoulder/back, nausea, vomiting, fever
• Physical exam: RUQ tenderness, Murphy’s sign = ↑ RUQ pain and inspiratory arrest with deep breath during palpation of R subcostal region, ± palpable gallbladder
• Laboratory evaluation: ↑ WBC, ± mild ↑ bilirubin, AΦ, ALT/AST and amylase; AST/ALT >500 U/L, bili >4 mg/dL or amylase >1000 U/L → choledocholithiasis
Diagnostic studies
• RUQ U/S: high Se & Sp for stones, but need specific signs of cholecystitis: GB wall thickening >4 mm, pericholecystic fluid and a sonographic Murphy’s sign
• HIDA scan: most Se test (80–90%) for acute cholecystitis. IV inj of HIDA (selectively secreted into biliary tree). In acute cholecystitis, HIDA enters BD but not GB. 10–20% false 
(cystic duct obstructed from chronic cholecystitis, lengthy fasting, liver disease).
Treatment
• NPO, IV fluids, nasogastric tube if intractable vomiting, analgesia
• Antibiotics (E. coli, Klebsiella and Enterobacter sp. are usual pathogens) ([2nd- or 3rd-generation cephalosporin or FQ] + MNZ) or piperacillin-tazobactam
• Early CCY (usually w/in 72 h). Delaying surgery 2–3 mo ↓ operative time w/o Δ rate of complications or conversion to open procedure (Am J Surg 2008;194:40).
• If unstable for surgery, EUS-guided transmural or ERCP-guided transcystic duct drainage is equivalent to cholecystostomy (Gastro 2012;142:805)
• Intraoperative cholangiogram or ERCP to r/o choledocholithiasis in Pts w/ jaundice, cholangitis or stone in BD on U/S
Complications
• Gangrenous cholecystitis: necrosis w/ risk of empyema and perforation
• Emphysematous cholecystitis: infection by gas-forming organisms (air in GB wall)
• Post CCY: bile duct leak, BD injury or retained stones, cystic duct remnant, sphincter of Oddi dysfxn
CHOLEDOCHOLITHIASIS
Definition
• Gallstone lodged in bile duct (BD)
Epidemiology
• Occurs in 15% of Pts w/ gallbladder stones; can form de novo in BD
Clinical manifestations
• Asymptomatic (50%)
• RUQ/epigastric pain due to obstruction of bile flow → ↑ BD pressure, jaundice, pruritus, nausea
Diagnostic studies
• Labs: ↑ bilirubin, AΦ; transient spike in ALT or amylase suggests passage of stone
• RUQ U/S: BD stones seen ~50% of cases; usually inferred from dilated BD (>6 mm)
• ERCP preferred dx modality when likelihood high; cholangiogram (percutaneous, operative) when ERCP unavailable or unsuccessful; EUS/MRCP to exclude BD stones when suspicion low
Treatment
• ERCP & papillotomy w/ stone extraction (± lithotripsy)
• CCY typically w/in 6 wk unless contraindication (>15% Pts will develop indication for CCY if left unRx’d)
Complications
• Cholangitis, cholecystitis, pancreatitis, stricture
CHOLANGITIS
Definition & etiologies
• BD obstruction → infection proximal to the obstruction
• Etiologies: BD stone (~85%)
Malignant (biliary, pancreatic) or benign stricture
Infection w/ fluke (Clonorchis sinensis, Opisthorchis viverrini)
Clinical manifestations
• Charcot’s triad: RUQ pain, jaundice, fever/chills; present in ~70% of Pts
• Reynolds’ pentad: Charcot’s triad + shock and Δ MS; present in ~15% of Pts
Diagnostic studies
• RUQ U/S
• Labs: ↑ WBC, bilirubin, AΦ, amylase; BCx
• ERCP; percutaneous transhepatic cholangiogram (if ERCP unsuccessful)
Treatment
• Antibiotics (broad spectrum) to cover common bile pathogens (see above) ampicillin + gentamicin (or levofloxacin) ± MNZ (if severe); carbapenems; pip/tazo
• ~80% respond to conservative Rx and abx → biliary drainage on elective basis
• ~20% require urgent biliary decompression via ERCP (papillotomy, stone extraction and/or stent insertion). If sphincterotomy cannot be performed (larger stones), decompression by biliary stent or nasobiliary catheter can be done; otherwise percutaneous transhepatic biliary drainage or surgery.