Biliary Tract Disease

August 26, 2014

V. Raman Muthusamy, MD, FACG, FASGEDirector of Interventional Endoscopy

Clinical Professor of MedicineDavid Geffen School of Medicine at UCLA

Gallstones

• Common: about 20-30 million in US• Gender and Ethnic Predisposition- Over 65% are female- Hispanic and Native American

• Lower socioeconomic status• 700,000 annual cholecystectomies in

U.S.• $6.5 billion annual cost

Ultrasound Images

Natural History of Gallstones

• Mostly asymptomatic: 70-90%• 2-4% develop symptoms annually- 10-20% with symptoms have CBD stones

• If symptomatic, frequently recurs (40%)• Gracie and Ransohoff- 5 yrs: 10% symptomatic

- 10 yrs: 15% symptomatic- 15 yrs: 18% symptomatic- No sig complications

Ann Intern Med 1983;99:199-205

Types of Gallstones

• Cholesterol

- Most Common (75%)

• Pigmented: usually black

- 20% stones

• Brown

- More common in Asia

Stones

Cholesterol stones

• Obese women• Rapid weight loss: RYGB, lap band• Terminal ileal resection or disease- Crohn’s disease

• Pregnancy: saturation and poor motility• Drugs: estrogen, OCPs, TPN, octreotide• Genetics• Hypertriglyceridemia, DM, ? vagotomy

Cholesterol Gallstone

• Cholesterol saturation and Dysmotility• Nucleation- Calcium nidus- Defective acidification- Nucleation vs. Anti-nucleation factors

• Growth- Gallbladder dysmotility (TPN,

pregnancy, octreotide)- Gallbladder mucus

Pigmented Gallstones

• Bilirubin deconjugation and precipitation

- Bacterial β glucuronidase

• Chronic hemolytic disorders

- Sickle cell, thalassemias

• Chronic liver disease: ie. Cirrhosis

• Gallbladder stasis• Older age and women

• Disrupted enterohepatic circulation

- TI resection, Crohn’s disease

Brown stones

• Seen with chronic infections of biliary tree

- Bacterial and parasitic• Asian-pacific ethnicity

• Prior surgery of biliary tree

- Stasis and dilation of duct system

- Often after cholecystectomy

• Recurrent pyogenic cholangiopathy

Gallbladder Sludge

• Mixture of crystals and mucus

• Can cause the same symptoms as stones• Can be transient

• Diagnosed on ultrasound

• Nonshadowing

KUB of calcified gallstones

CT scan of gallstones

Complications of Cholelithiasis

• Biliary colic• Cholecystitis

• Fistulization (GB to duodenum)• Mirizzi syndrome

• Cholangitis

• Pancreatitis

• GB cancer

Biliary Colic

• RUQ, mid-epigastric• Lasts hours not weeks

- Crescendo, plateau, and then relief• Often post-prandial

- Nocturnal awakening

- Many hours after meal

• Nausea and vomiting

• Radiation to shoulder and back

Acute Cholecystitis

• Duration: hours to days• Cystic duct obstruction

• HIDA scan: Sens/Spec > 90%• Ultrasonography: Sens/Spec > 90%

• Alk phos, transaminases rarely twice normal

• Mortality: 5-10% advanced age, co-morbidities, complications

Acute Cholecystitis Complications

• Emphysematous cholecystitis

- Gangrenous gallbladder

• Perforation• Mirizzi Syndrome

- Cystic duct stone leading to biliary obstruction

• Cholecystoenteric fistula

- Pneumobilia

- Duodenum, Colon, Jejunum, Stomach

- Gallstone ileus

Mirizzi’s Syndrome

Cystic Duct Stone Compressing CBD

Cholescintigraphy (HIDA)False Positives

• Prolonged fasting

• Liver disease

- Tracer absorbed too slowly

• Chronic cholecystitis

• Total parenteral nutrition• Critical illness

Board Questions

76 yo male

• In ICU for recent STEMI, moderate failure• On ventilator, stormy course; NPO,

distended abdomen

• No prior abdominal surgeries• Low grade fever, leukocytosis

• Tenderness in RUQ, no rebound• Increasing AST, ALT and alk phos

- Bilirubin normal

What is the most likely diagnosis??

A. Mirizzi’s syndrome

B. Choledocholithiasis

C. Ascending cholangitis

D. Acalculus cholecystitis

What is the best therapy in the critically ill patient??

A. Lap cholecystectomy

B. ERCP with sphincterotomy

C. Percutaneous cholecystotomy

D. Observation

Acalculous Cholecystitis

• Older; male > female• Triad

- Hemodynamic instability

- Prolonged fasting

- Immobility

• Fever, RUQ pain, leukocytosis, tenderness may be absent

• More fulminant course

Acalculous Cholecystitis

• RUQ sonogram- GB wall > 4 mm*

- Sonographic Murphy’s sign

- Pericholecystic fluid collection

- Sensitivity: 67-92%

- Specificity: > 90%

• CT scan- GB wall > 4 mm

- Subserosal edema

- Intramural gas

- Sloughed mucosa

- Sens / Spec >95%

• Scintigraphy- False (+) and (-)

NB. Ascites without other cause

Acalculous Cholecystitis

• Treatment- Urgent

cholecystectomy

- Percutaneous drainage

Cholecystectomy

• Open or laparoscopic: 0.1% mortality

• Laparoscopic: reduction in postoperative LOS and pain

• Complicated presentation, coagulopathy or adhesions->open

• IOC: allows for ID and potential treatment of choledocholithiasis

Complications of Cholecystectomy

• Overall incidence: ~1% in recent series• Types:

- Bile leak without significant duct injury

- Major duct injury +/- leak• Transection, stricture etc

• Typically treat leaks with ERCP with stent placement for 4-6 weeks without sphincterotomy (90% success rate)

• Endoscopic therapy similar to surgery for major biliary injury except for disconnection

ERCP with Stent placement for CBD Leak

Before After (Healed)

Other Treatment Modalities

• Ursodeoxycholic acid

- Patent cystic duct and non-calcified stones

- Small floating stones best response

- High recurrence rate (>50%)

- Risk of pancreatitis and cholangitis• ESWL not approved in U.S.

• Cholecystostomy tube

Gallbladder Dyskinesia

• Decreased GB ejection (via CCK-HIDA) fraction may predispose to gallstone formation

• Controversial whether cholecystectomy leads to symptomatic improvement

• More common in subjects with functional bowel disorders

Gallbladder Polyps

• Common: 1-5% of population• > 95% non-neoplastic (mostly cholesterol)

• Follow with ultrasound for 6 month-1 yr intervals

• If growth > 10 mm, cholecystectomy

• If no growth after 2 yrs, can dispense surveillance

• GB polyp (any size) + PSC = surgery

Gallbladder Polyps

• Cholesterolosis: Most common (60%)

• Adenomyomatosis (25%)

• Inflammatory (10%)

• Adenoma: rare

- May be precursor to GB cancer

Gallbladder Polyps

• Cholesterolosis

- Cholesterol / TG within epithelial macrophages

- Local or diffuse

- Can be combined with cholesterol polyps

- 10-15% autopsy series

- Ultrasound remains best way to detect

- Rarely thought to be symptomatic

Cholesterol vs adenomatous polyp

Gallbladder Polyps

• Adenomyomatosis

- Hypertrophy of the muscle layer

- Usually focal (fundus) although can be diffuse

- Incidental and asymptomatic

- Classic comet tail appearance on US

- Surgery when wall > 10 mm, associated mass or in rare instances with diffuse disease

“Comet sign” of Adenomyomytosis

GB Cancer

Incidence: 5000/yr in US; 1-2% of GB surg

Late diagnosis commonSurgery only curative option

- Radical Cholecystectomy

5 yr survival: <10%Associations:

- Female gender, Caucasian race, increasing age- Porcelain gallbladder- PSC and IBD- Anomalous pancreaticobiliary junction (APBJ)- Cholelithiasis- Chronic Salmonella typhi- Adenomatous GB polyps

Gallbladder Cancer

Choledocholithiasis

• Can present with biliary colic

• Elevated liver profile • Dilated common bile duct: when chronic

• Jaundice

• Ascending Cholangitis• Pancreatitis

Ascending Cholangitis• Infection of CBD: Emergency

- Duct usually obstructed: stones, stent, parasite

- Abnormal duct: post-op, stricture, anastomosis

• Usually bacterial: E coli: 25-50%

- Klebsiella: 15-20%; Enterobacter: 5-10%

- Enterococcus: 10-20%• Treatment: Resuscitate

- Antibiotics: Broad spectrum (if ill, cover enterococcus)

- Relieve obstruction: ERCP, perc drain, surgery

Ascending Cholangitis: 15-50%

Charcot’sTriad

Fever

RUQ Pain

Jaundice

Reynold’s Pentad: Add MS changes, shock

Choledocholithiasis

• Recurrent biliary colic in the post-cholecystectomy patient

• ERCP for patients with high probability

- 95% success rate

- 5% complication rate

• For low or intermediate probability

- MRCP – usually for low probability

- EUS – often for intermediate probability

Choledocholithiasis

• Biliary sphincterotomy

• Balloon / basket extraction

• Balloon sphincteroplasty

- For larger stones; usu after small sphincterotomy

• Lithotripsy

- Mechanical (basket)

- Cholangioscopy

• Laser

• Electrohydraulic (EHL)

- Extracorporeal shockwave lithotripsy

Sphincter of Oddi Dysfunction

• Stenosis or spasm of the Sphincter of Oddi• Persistent / recurrent biliary pain following

cholecystectomy without structural abnormalities

• Idiopathic recurrent pancreatitis- Recent study shows no advantage to dual

sphincterotomy over biliary sphx alone

• Biliary type pain with intact gallbladder and no stones

Sphincter of Oddi Dysfunction

• Type I:

- biliary type pain, elevated liver enzymes (> 2x nl on two occasions)

- bile duct diameter > 12 mm on ERCP

- delayed contrast drainage > 45 minute• Type II: biliary type pain and 1 or 2 of the

aforementioned criteria

• Type III: biliary type pain only

Rome III criteria: Doesn’t include contrast drainage as a criteria.

Sphincter of Oddi Dysfunction

• Type I: empiric biliary sphincterotomy

• Type II: sphincter of Oddi manometry (SOM)

- Abnormal in up to 50-63% pts

- Pain relief up to 85% in this subset with biliary sphincterotomy

- Normal SOM and sphincterotomy: controversial

Sphincter of Oddi Dysfunction

• Type III:

- Less than 10% response to sphincterotomy

- NIH sponsored trial recently published in JAMA shows NO benefit for manometric testing and sphincterotomy

- ERCP +/- SOM no longer recommended

- Consider other treatments for functional bowel disorders

Cotton et al, JAMA 2014, 311:(20)

Sphincter of Oddi Manometry

Basal pressure > 40 mm HgCorrelates best with presence

of symptoms and relief following sphincterotomy

Choledochal Cysts

• Congenital anomalies of the biliary tree

• Incidence: 1/100-150,000• 15-100 x more common in Japan

• Females more commonly affected (3-4:1)

• 2/3 cases manifest by age 10• More seen in adults recently

• Classic triad: Abd. Pain, jaundice, palpable mass

Choledochal Cysts• Type I: (most common) 80-90% of cases.

Fusiform dilation of CBD (segmental or diffuse)

• Type II: Choledochal diverticulum: 2%• Type III: Choledochocele (intraduodenal

dilation): 1-5%• Type IV: Multiple extra +/- intrahepatic

cysts

- 10%, divided into and A and B type• Type V: Multiple intrahepatic dilation

(Caroli’s disease): rare, but up to 20% in some series

Choledochal Cysts• Association with anomalous union of pancreatic

and biliary ducts (seen in 50-80%)- Recommend cholecystectomy for GB CA risk

• Jaundice, abdominal pain, intraductal stones• At risk for cholangiocarcinoma (esp. I and IV)

- Risk of 10-30%; 20-30 x gen. population

• Surgical excision for most cysts- Type III: Large biliary sphincterotomy

• Caroli's disease associated with congenital hepatic fibrosis, renal tubular ectasia and polycystic kidney disease

Todani classification

Board Questions

• 39 yo male presents with pruritis, jaundice and pain

• No prior PMH or PSH• FH is non-contributory• PE: scleral icterus, mid-

epigastric tenderness• LABS: Alk phos: 487,• Bili: 5.2, AST: 164, ALT:

628• CT on right panel

revealed no stones:

Coyle in GASTRO 2010;138:e3–e4

Board Question

• Endoscopy reveals bulge at ampulla

Coyle in GASTRO 2010;138:e3–e4

Board Question 1: What is the most likely diagnosis?

• A. Choledocholithiasis• B. Peri-ampullary diverticulum

• C. Choledochal Cyst• D. Ampullary adenoma

• E. None of the above

Board Question 2: What is the best treatment?

• A. Observation• B. Ampullectomy

• C. Whipple resection• D. Sphincterotomy

• E. None of the above

Board Question Answer

• This is a choledochal cyst, Type III

• Aka Choledochocele• Can usually be

treated by large, biliary sphincterotomy that unroofs the cyst

Coyle in GASTRO 2010;138:e3–e4

Summary

• Stone disease: Common- Know the types and pathogenesis- Know the complications and treatment

• Gallbladder polyps- Know the types and natural history

• Acalculous cholecystitis- Recognize and treat

• Choledocholithiasis:- Know how to diagnose and treat

Summary

• Ascending Cholangitis: Recognize, urgent treatment- Know organisms and causes

• Sphincter of Oddi dysfunction

- Know sub-types and treatment• Choledochal cysts- Know types, natural history and

treatment