The Biliary TractRaymond W Pryor III M.D.

July 31, 2008

History

History

Circa 200 AD – Galen – the gallbladder as a subsidiary organ for the liver & responsible for yellow bile

Renaissance period – Gallbladder seat of many emotions (gall)

1652 - Thomas Bartholin – gallbladder part of bile tract from liver to intestine

1654 - Thomas Glisson – formed more detailed anatomy of liver & biliary tract

More relevant history

1420 - Antonio Benevieni – 1st account of gallstones

1687 - Stal Pert Von Der Wiel – 1st operation on gallstones

1733 – Jean-Louis Petit -1st successful removal of gallstones with fistula formation

1859 – J.L.W. Thudichum – Two stage cholecystostomy

July 15, 1867 – Dr John Stough Bobbs – Single stage cholecystostomy

Still More relevant History

1630 & 1667 – Zambecarri & Teckoff – proved the gall bladder not essential to life

1878 - Theodor Kocher – refined cholecystostomy procedure

July 15, 1882 – Dr Langenbuch – 1st open cholecystectomy

1886 – cholecystotomy 27% mortality vs 12% mortality for Langenbuch’s cholecystectomy – became gold standard

1940’s – Mirizzi introduced cholangiography for CBD stones

Into the Laparoscopic Age

Trocar insertion 1st described by Ezekiel and Celsus – 25 BC – AD 50

Term “Trocar” coined in 1706› “trocarter troise-quarts”

1901 Dimitri OH – gynaecologist, performed 1st endoscopic exam

1911 – Dr Bernheim published “Organoscopy” in Annals of Surgery

1938 Veress developed spring-loaded needle

Laparoscopic development

1952 – quartz rod to project light 1959 – closed circuit television 1966 – Kurt Semm – automatic insufflator device,

thermo coagulation, irrigation & aspiration system and endoloop applicator

1978 – Dr Hasson – direct placement of trochar 1982 – Liver biopsy via laparoscopy 1987 – Dr Mouret – 1st laparoscopic

cholecystectomy on human By 1989, procedure being done in US 1992 – NIH concluded Laparoscopic

cholecystectomy treatment of choice

Anatomy

Anatomy

Variations in Bile Ducts

Biliary Physiology

Overall, the purpose is to modify, store and regulate the flow of bile

The gallbladder concentrates & stores bile, then releases bile in response to a meal

Biliary duct secretion of chloride-rich fluid controled by secretin, cholecystokinin (CCK) and gastrin.

Gallbladder physiology

Gallbladder wall has no muscularis mucosa or submucosa

Predominantly columnar epithelial cells

Rokitansky-Aschoff sinuses

Ducts of Luschka

Gallbladder physiology

Normal capacity of 40-50 mL Liver secretes >600 mL of bile daily Gallbladder mucosa has greatest

absorptive capacity per unit area of any structure in body

Concentrates bile 5-10 fold NaCl transport by epithelium is driving

force and water passively absorbed

Composition of BileCharacteristic (mEa/L)

Hepatic Gallbladder

Na 160 270

K 5 10

Cl 62-112 1-10

HCO3 45 10

Ca 4 25

Water 95-98% 85-90%

Bilirubin 1.5 15

Protein (mg/dL) 250 700

Bile Acids 3-50 290-340

Phospholipids 8 40

Cholesterol (mg/dL)

60-70 350-930

Total Solids -- 125

pH 7.0 - 7.8 6.0 - 7.2

Biliary Motility

Filling is facilitated by contraction of ampullary sphincter (Sphincter of Otti)

Goes through cycles of partial emptying of 10-15% of volume to mix & concentrate bile

After meal, sphincter of Oddi relaxes & CCK released—causing contraction of gallbladder

When stimulated, 50-70% of contents ejected over 30-40 minutes

Refills over next 60-90 minutes

Bacteriology

Under “normal” conditions, the biliary tract is sterile

Positive cultures found:› 11-30% symptomatic stones & chronic

cholecystitis› 46% of acute cholecystitis› 58% with gallstones & CBD stones without

cholangitis› 94% with gallstones, CBD stones and

cholangitis

Organisms Gram-negative aerobes most common

› E. coli› Klebsiella› Pseudomonas› Enterobacter

Gram-positive aerobes› Enterococcus› Streptococcus viridans

Anaerobes (~25%)› Bacteroides fragilis› Clostridium

Fungal› Candida sp.

Parasitic› Opisthorchis sp. (Thailand) (Liver fluke)› Clonorchis sp. (China)

Approximately 50% of positive cultures will have 2 or more different bacteria species present

Antibiotic Choice 2008 Sanford Guide

Cholecystitis (E. coli, Klebsiella, Enterococci)› meropenem (Merrem)› piperacillin/tazobactam (Zosyn)› cefepime (Maxipime)

cefazolin + ampicillin (Ancef + ampicillin) ciprofloxacin + metrodazole (Cipro + Flagyl)

Emphysematous Cholecystitis (Clostridium perfringens +/- E. coli)› meropenem (Merrem)› piperacillin/tazobactam (Zosyn)

ertapenem (Invanz) ticarcillin./clavulanate (Timentin)

Cholangitis› meropenem (Merrem)› cefepime (Maxipime)› piperacillin/tazobactam (Zosyn)› Tigecycline (Tygacil)

ampicillin/sulbactam (Unasyn) imipenem/cilstatin (Primaxin) cefoperazone (Cefobid)

Antibiotics (cont’d)

PO Treatment of cholecystitis or cholangitis› clindamycin (Cleocin)› ciprofloxacin + metronidazole (Cipro + Flagyl)› levofloxacin (Levoquin)› moxifloxacin (Avelox)

Opisthorchis sp. & Clonorchis sp. (Liver fluke)› praziquantel (Biltricide)› albendazole (Albenza) **poor response to

above organisms

Gallstones

Cholelithiasis

Formation represents failure to maintain bile components (cholesterol, Ca, bile pigments) in a solubilized state

Majority of those with stones are asymptomatic

1-2% of asymptomatic individuals develop symptoms per year

Approx 65% of asymptomatic patients remain symptom free after 20 years

Cholesterol Gallstones

75% of all gallstones in United States

3 stages of formation› Cholesterol

supersaturation› Crystal nucleation› Stone growth

Risk factors› Female› Multi gravid› Estrogen use› Old age› Obesity› Rapid weight loss› Prolonged TPN

Pigment gallstones

25% of stones in US, 65% in Japan Black Pigment

› Made of Ca bilirubinate, bilirubin polymers & bile acids› Increased concentration of bilirubin & Ca › Hemolytic disorders & cirrhosis› Chronic TPN› Ileal resections› Exact mechanism unclear, may be due to presence of

bacterial b-glucuronidase that deconjugates bilirubin Brown Pigment

› Asian populations› Infection & bacterial hydrolysis of bilirubin› More commonly found in bile ducts

Biliary Sludge

Viscous bile Precursor to

gallstone formation Associated with

prolonged TPN and fasting

Often found during ultrasound evaluation

Usually asymptomatic

Is Everyone Still Awake?

Diagnosis of cholelithiasis Abdominal plain film

› rarely useful as 10-15% of stones radiopaque enough to be seen Ultrasound

› Non-invasive and cost-effective› 95-98% sensitive, 98% specific for documenting presence of gallstones› 80-95% sensitive, 78-80% specific for cholecystitis› Operator dependant

Radionuclide scan – hepatobiliary iminodiacetic acid (HIDA)› Good for detecting cystic duct obstruction or CBD obstruction› Also very useful in determining bile leaks after cholecystectomy› Acute cholecystitis: 94% sensitive, 65-85% specific› Chronic cholecystitis: 65% sensitive, 6-10% specific› Overall false positive (no filling of cystic duct or gallbladder) 15-20%

This is lowered with administration of morphine to 2-5% CT scan

› Less sensitive than ultrasound for detecting stones (50-70%) or cholecystitis.› More expensive

MRCP› Cost prohibitive› Most often used to detect common bile duct obstruction

Ultrasound

More images

CT Scan

MRCP

MRCP with morphine

Chronic Calculous Cholecystitis

Recurrent cystic duct obstruction & inflammation Presents with biliary colic Association with meals present in only 50% Symptoms

› Pain duration 1-5 hours (rare >24 hrs or <1 hr)› Nausea & vomiting present 60-70% of time› Bloating & belching in 50%› Fever & jaundice rare

Exam may be normal unless during attack Laboratory values usually normal Differentials include: GERD, PUD, IBS, pancreatitis Treatment is elective laparoscopic cholecystectomy

Chronic Calculous Cholecystitis

Xanthogranulomatous cholecystitis

Variant of chronic cholecystitis lipid-laden inflammatory process comparable to

xanthogranulomatous pyelonephritis Marked wall thickening with intramural nodules

visible on CT and US Cannot distinguish radiographically from gallbladder

carcinoma

Porcelain gallbladder

Rare disorder where chronic cholecystitis causes mural calcification of gallbladder wall

Cholecystectomy is warranted as there is a 30-65% risk of underlying gallbladder carcinoma

Acute Calculous Cholecystitis Related to gallstones 90-95% of cases

› Non-resolving obstruction of cystic duct usually triggering event Can lead to ischemia and necrosis of gallbladder wall in 5-18% 46% will have positive bile cultures 75% will have had previous, less severe, attack of biliary colic Symptoms:

› RUQ pain lasting hours to days› Pain usually unremitting› Nausea, vomiting, anorexia & fevers common› Positive Murphy’s sign› Elevated alkaline phosphatase & WBC

Management:› NPO and IV fluids› Pain control (avoid narcotics if possible)› Antibiotics

Treatment is Laparoscopic cholecystectomy› Delayed vs immediate

Acute Calculous Cholecystitis

Acute Acalculous Cholecystitis

5-10% of all patients with acute cholecystitis occur in absence of stones Frequently progresses to gangrene, empyema or

perforation Common following trauma, burns, long-term TPN, AAA

repair or cardiac bypass Exact etiology unclear, but may be related to ischemia

& stasis Symptoms similar to Acute Calculous cholecystitis HIDA scan has 40% false positive rate Emergency cholecystectomy or percutaneous

cholecystostomy is treatment of choice Mortality as high as 40% in some studies, due to

concomitant illnesses

Acute Acalculous Cholecystitis

Complications of cholecystitis

Suppurative cholecystitis may lead to sepsis and shock

Perforation in 3-10% of cases (most contained by surrounding structures)

Emphysematous cholecystitis› Most common in poorly

controlled diabetics› Usually caused by

Clostridium perfringens› Gas seen in gallbladder

wall

Gallstone Ileus

Large gallstone the obstructs small bowel (distal ileum at ileocecal valve)

Fistula between gallbladder and duodenum (can be colon or stomach)

Most commonly in elderly (>70) females History of gallstone-related symptoms present in only 50% Only account for <1% of SBO cases <0.1% of those with gallstones will develop Up to 25% of SBO in elderly patients who have not had

previous abdominal surgery or have a hernia Treat with Ex-lap and enterotomy with removal of stone. Take

back for takedown of biliary-enteric fistula & cholecystectomy when more stable

On the ABSITE every year!!!

Gallstone Ileus

Intrahepatic Stones

AKA Hepatolithiasis Most common in East

Asian population Most associated with

biliary strictures, primary sclerosing cholangitis, choledochal cysts & biliary tract tumors

Spontaneous in <10% of cases

Treatment depends on location & underlying condition(s)

Choledocholithiasis

7-15% of patients undergoing cholecystectomy have CBD stones

Findings of jaundice, lightening of stool & dark urine

Fevers & elevated WBC indicate cholangitis

Serum Bilirubin has PPV of 28-50%

Biliary obstruction may be partial or transient, so labs may be normal in up to 30%

Choledocholithiasis (cont’d)

May have overlying pancreatitis (up to 45% of all cases of pancreatitis)

Dilated CBD in 58% of patients Ultrasound only 60-70% sensitive for CBD stones MRCP 95% sensitive & 89% specific ERCP Gold Standard

› Can both diagnose and treat 90% of time› Pancreatitis occurs in up to 5% of Patients

If unable to remove stone with ERCP (or none available) need to do laparoscopic or open CBD exploration

Stone found in CBD within 2 years of cholecystectomy is termed retained, >2 years is recurrent

Cholangitis

Acute bacterial infection of biliary tract Most common cause of biliary obstruction as often associated with

choledocholithiasis Occurs in 4-7% of ERCP and PTC (Percutaneous transhepatic

cholangiography) Other causes of obstruction associated with cholangitis:

› Strictures, neoplasms (rare), chronic pancreatitis, congenital cysts, duodenal diverticula

Presentation of fever, RUQ pain, jaundice › Charcot’s triad

May also have Hypotension & mental status change› Reynold’s pentad

Lab findings: Leukocytosis, elevated alk phos, AST, ALT, Bilirubin (direct)

Blood cultures positive 40-50% CT scan or Ultrasound can help make diagnosis

Treatment of Cholangitis

Immediate IV antibiotics and fluid resuscitation

If no response within 24 hours (15%), or in those with toxic cholangitis, emergency biliary decompression necessary› Endoscopic or percutaneous› May need open CBD exploration & T-tube

placement (higher mortality) Overall mortality 2% (5% with toxic

cholangitis) On ABSITE every year

Primary Sclerosing Cholangitis

Choleststic liver disease characterized by fibrotic strictures in the intrahepatic and extrahepatic biliary tree in ABSENCE of any known cause.

Associated with HLA B8/DR3, IDDM, Graves’ Disease, Sjögren’s syndrome, & Myasthenia gravis

Clinical presentation highly variable› Jaundice, pruritus, fatigue, abnormal LFT’s

Mean age 40-45 years Male : female 3:1 Diagnosis by ERCP Median survival after diagnosis 10-12 years Primary treatment is liver transplantation

Sclerosing cholangitis

Sclerosing cholangitis caused by stones, cholangitis or operative trauma termed Secondary sclerosing cholangitis

Choledochal cysts

Rare congenital dilation of biliary tract

1 : 150,000 incidence in Western countries

Much more common in Japan

Female : male 8:1 Most often diagnosed

in infancy Treatment is

resection

Biliary Strictures & Bile duct injury 80-90% caused by iatrogenic

injuries Laparoscopic cholecystectomy

most common Present days to weeks after

surgery May be years after surgery as

scar tissue obstructs duct Treatment is decompression,

drainage, possible surgical resection.

Stenting being used with increasing frequency

With ligation of CBD & strictures, need Roux-en-Y hepaticojejunostomy

Gallbladder Cancer

5th most common GI tract malignancy 2-3 times more common in females 75% over age 65 5,000 new cases in US annualy Found incidentally in 1% to 3% of

cholecystectomy specimens Majority of the time, diagnosed in late stages

with distant mets Cholelithiasis present in 75-90% of cases

› Only 0.4% of those with gallstones develop cancer

Gallbladder Cancer Over 90% are adenocarcinoma

› 60% scirrhous, 25% papillary, 15% mucoid Squamous cell, oat cell, undifferentiated,

adenosquamous & carcinoid tumors less common Only 10% are correctly diagnosed preoperatively 1-3 out of every 100 cholecystectomy

specimens will show carcinoma at pathology At diagnosis:

› 25% contained to gallbladder wall› 35% metastases to regional lymph nodes› 40% have metastasized to distant sites

Average survival is 6 months after diagnosis

Lymphatic drainage & spread

Initial drainage to cystic duct node

Descents along CBD nodes

Nodes at posterior head of pancreas

Interaortocaval nodes

Can also spread by direct invasion into liver

Gallbladder Cancer Most commonly presents with RUQ pain Weight loss, jaundice, palpable mass very late findings Many report change in quality or frequency of biliary colic

episodes US sensitivity 70-99% CT approx 75% sensitive MRI 90-99% sensitive

Management & Prognosis Tumor confined to mucosa or

submucosa (T1a) or to muscularis (T1b) have overall 5-year survival of 100% & 85%

Spillage of bile during cholecystectomy can seed abdomen

Invasion beyond muscularis (T2 & T3) need extended cholecystectomy with lymph node dissection

Stage III has ~15% 5-year survival

Stage IV has median survival of 1-3 months from diagnosis

Majority of cases, therapy is palliative

Chemo & radiation hot been shown to increase survival

Survival following radical resection of T2 gallbladder

cancer vs simple cholecystectomy

Cholangiocarcinoma

Uncommon tumor anywhere along intrahepatic or extrahepatic biliary tree

60-80% occur at bifurcation Most present with obstructive jaundice, hepatomegaly,

palpable gallbladder (Courvoisier’s sign) or cirrhosis (advanced disease)

2,500-3,000 new cases in US annualy Mean age in 50’s, men & women equal Increased risk with choledochal cysts, intrahepatic

stones, Liver flukes, dietary nitrosamines & exposure to dioxin

Following biliary-enteric anastomosis, 5% will develop Tend to spread by direct extension

Staging & classification

Intrahepatic tumors (Klatskin tumors)treated like hepatocellular carcinoma (hepatectomy)

Perihilar treated with resection with local hepatic resection

Distal treated like periampullary tumors with pancreatoduodenectomy (Whipple)

TNM staging

Diagnosis

Intrahepatic easily visualized on CT scan

Perihilar & distal tumors difficult to visualize on US and CT

ERCP & MRCP have near equal sensitivity (85-95%)

Most patients have serum Bilirubin >10, elevated Alk Phos & CA 19-9

Treatment

Preoperative placement of stents in hepatic & hilar tumor

Resected Left lobe & hilum with reconstruction

Prognosis

Long-term survival highly dependant on stage & treatment

For resectable intrahepatic tumors, overall 5-year 30-40%

Resectable peri-hilar tumors 10-20%

Resectable distal tumors 28-45%

Median survival for all unresectable tumors is 6-7 months

Miscellaneous Biliary Pathologies Biliary atresia

› Most common cause of persistent jaundice in newborn› Treat with hepatic portoenterostomy (Kasai procedure)

or transplantation Hemobilia

› Most cases in US due to trauma or iatrogenic injury› Diagnosis often requires arteriography› Treatment of persistent hemobilia includes

embolization or surgical ligation Benign polyps of gallbladder

› From cholesterol laden macrophages in mucosa Papilloma of bile duct

› Very rare, only ~90 cases in literature

Mirizzi Syndrome

Rare cause of biliary duct obstruction

Large stone contained within gallbladder compresses the CBD

Local spread of inflammation from gallbladder to CBD may also result in duct narrowing

The End