A 95 year-old woman presented with upper abdominal pain and jaundice;
ultrasound demonstrated gallstones. Symptoms were short in duration, and
jaundice began to clear rapidly. In view of her age and improving condition,
she was treated conservatively for cholecystitis. However, she then
developed protracted vomiting; endoscopy demonstrated several stones in
the duodenum.
What is the most likely cause this type of complication?
a. Malignancy extending into duodenum
b. Perforation of gallbladder
c. Caroli’s syndrome
d. Metastasis from another primary tumor
Diseases of the Gallbladder
and Biliary Tract
Driss Raissi, MD
New York State University
Downstate Lecture Series
Normal Biliary Physiology
Liver produces 500-1500 mL of bile/day
Major physiologic role of biliary tract and
GB is to concentrate bile and conduct it in
well-timed aliquots to the intestine.
In the intestine:


bile acids participate in normal fat digestion
Cholesterol and other
endogenous/exogenous cmpds in bile
excreted in feces.
Biliary Physiology
Complex fluid secreted by hepatocytes
Passes through hepatic bile ducts into common hepatic duct
Tonic contraction of sphincter of Oddi during fasting diverts ~1/2 of
bile through the cystic duct into the GB – stored and concentrated.
CCK – released after food ingestion 


GB contracts, sphincter of Oddi relaxes
Allows delivery of timed bolus of bile into intestine.
Bile acids – detergent molecules



Have both fat and water soluble moieties
Convey phospholipids and cholesterol from liver to intestine 
Cholesterol undergoes fecal excretion
Enterohepatic circulation
Bile acids
solubilize dietary
fat and promote
its digestion and
absorption
Enterohepatic
circulation:

Bile acids
efficiently
reabsorbed by SI
mucosa (terminal
ileum) 
recycled to liver
for re-excretion
Cholelithiasis
Normal Gallbladder
Velvety green mucosa
Thin wall
Tall columnar cells lining
mucosal folds (right)
Submucosa and
muscularis at the left.
Cholelithiasis
Gallstones:


MCC biliary tract
disease in US (2035% by age 75)
2 types:
Cholesterol (75%)
Pigment

Calcium bilirubinate
and other calcium
salts
Cholesterol Stones
Cholesterol:



Insoluble in water
Normally carried in bile solubilized by bile acids and
phospholipids
In most individuals, bile contains > cholesterol than can be
maintained in stable solution
“supersaturated” with cholesterol  microscopic cholesterol crystals
form
Interplay of nucleation (mucus, stasis) and “anti-nucleating”
(apolipoprotein A-I) factors determine whether cholesterol gall
stones form
Gradual deposition of cholesterol layers 

macroscopic cholesterol stones
Cholesterol Stones
Gallbladder:

key to stone formation

Area of bile stasis  slow crystal growth


Provides mucus or other material to act as a nidus for initiating
cholesterol crystal.
Mexican Americans and several American Indian tribes,
particularly the Pima Indians in the Southwest
high prevalence rates of cholesterol gallstones
↓bile acid secretion is believed to be the common denominator in
these ethnic groups
Pigment stones
Pathophysiology less well understood




 production of bilirubin conjugates (hemolytic
states)
 biliary Ca2+ and CO32Cirrhosis
Bacterial deconjugation of bilirubin to less
soluble form
Predisposing Factors
Factors that increase biliary cholesterol saturation:






Estrogens
Multiparity
OCP’s
Obesity
Rapid weight loss
Terminal ileal disease (decreases bile acid pool)
Factors that increase bile stasis:





Bile duct strictures
Parenteral hyperalimentation
Fasting
Choledochal cysts
Pregnancy – (GB hypomotility)
Clinical Manifestations
Most are asymptomatic
Duct obstruction - underlying cause of all manifestations

Cystic duct obstruction
distends GB  biliary pain
Superimposed inflamm/ifx  acute cholecystitis

Common duct obstruction
pain, jaundice, ifx(cholangitis), pancreatitis, and/or
hepatic damage 2° to biliary cirrhosis
Asymptomatic Gallstones
60-80% patients with gallstones in US

Over 20-year period:
18% of these develop biliary pain
3% require cholecystectomy
Prophylactic cholecystectomy considered in 3
high-risk groups:



1. Diabetics – 10-15% greater mortality
2. Calcified (porcelain) GB – Associated w/CA of GB
3. Sickle cell anemia –
hepatic crisis difficult to differentiate vs. acute cholecystitis
Porcelain Gallbladder
Treatment of Asx Gallstones
Chenodeoxycholic acid or Ursodeoxycholic acid

Dissolution of cholesterol stones
Expectant management  then cholecystectomy if
symptomatic disease develops = more cost effective
Alternatives:

Dissove cholesterol stones:
Instill Methyl-tert-butyl-ether or ethyl propionate into GB

Fragment stones:
extracorporeal shock wave lithotripsy
Extracorporeal Shockwave
Lithotripsy
Chronic Cholecystitis and Biliary Pain
Nonacute sx. caused by presence of gallstones
Biliary Pain (misnamed biliary colic)
GB from symptomatic patients may be grossly normal
Mild histologic inflammation with fibrosis and thickening often from
previous attacks of acute cholecystitis.
Symptoms:


From contraction of GB during transient obstruction of cystic duct by
gallstones.
Steady ache in epigastrium or RUQ 
comes on quickly  plateau over a few minutes  subsides gradually over
30 min-several hours
Referred pain at tip of scapula or right shoulder
N/V can accompany. (no fever, leukocytosis, or palpable mass)
Attacks occur at variable intervals (days – years)
Nonspecific symptoms:

Dyspepsia, fatty food intolerance, bloating and flatulence, heartburn, belching
Diagnosis
Ultrasonography

Sensitivity and specificity >95%
Oral cholecystograpy


90% sensitivity, 75% specificity
Reserved for ensuring cystic duct patency in pts
whom dissolution therapy or extracorporeal shock
wave lithotripsy is planned
Treatment
Laparoscopic cholecystectomy


Treatment of choice for recurrent biliary pain
May need preoperative endoscopic or radiologic examination of
CBD for concomitant choledocholithiasis
Open cholecystectomy


Mortality rate <0.5%
Might be required if difficulties during procedure i.e. adhesions,
obesity
NSAIDS

Several reorts and trials suggest that use during biliary pain
provides adequate pain relief and ↓ progression to acute
cholecystitis
Acute Cholecystitis
Acute Cholecystitis
Acute right subcostal pain and tenderness
from obstruction of cystic duct 
Distension, inflammation, and 2° ifx of GB
Acalculous cholecystitis (5%)



Triad - Prolonged fasting, immobility,
hemodynamic instability
Critically ill patients (burns, trauma, sepsis)
Parenteral hyperalimentation
Acute Cholecystitis
Epigastric or RUQ pain






Gradually  in severity and localizes to GB area
Unlike biliary pain, does not spontaneously resolve
Low grade fever, anorexia, n/v, right subcostal
tenderness
(+)Murphy’s sign
subhepatic tenderness and inspiratory arrest
during deep breath
Tender enlarged gallbladder (1/3)
Mild jaundice (20%) – concomitant CBD stones or BD
edema
Murphy’s Sign
Complications
Onset of fever, shaking chills, leukocytosis, abdominal pain or
tenderness, or persistent severe symptoms =

progression of disease and development of complications

Emphysematous cholecystitis
Diabetics with bacterial gas present in GB lumen and wall




Empyema of gallbladder
Gangrene
Perforation
Mirizzi’s syndrome
Profound jaundice in which extrinsic CBD compression occurs from
impacted stone in GB neck
Emphysematous
Cholecystitis
Diagnosis Acute Cholecystitis
Radionuclide scanning after
administration of 99mTc-DISIDA or HIDA


Most accurate test to confirm cystic duct
obstruction
If GB fills with isotope 
acute cholecystitis unlikely

If bile duct visualized but gallbladder not 
Clinical diagnosis strongly supported
Images taken shortly after
injection of the radiolabeled
tracer.
Gallbladder (black spot) fills as
radioactive material is secreted
into bile and floods in.
Images after gallbladder filled.
Emptying stimulated by an
injection of CCK
Enlarging black streak
representing the CBD appears
below the gallbladder.
As streak becomes visible, black
spot representing the GB ↓ in size
and almost disappears as bile is
squeezed into the small intestine.
Diagnosis Acute Cholecystitis
Ultrasonagraphy:

Gallstones (or sludge in acalculous) along
with localized tenderness over the GB,
pericholecystic fluid, and GB wall thickening
strong supportive evidence for acute cholecystitis
Oral cholecystograms = no clinical use

Unreliable in acutely ill patient
Management of Acute Cholecystitis
Patients may improve over 1-7 days with
expectant management


NG suction for profound vomiting, and/or abdominal distension
IV fluids, ABX, and analgesics
Cholecystectomy



Because of high risk of recurrent acute cholecystitis
Within first 24-48 hours after acute episode
Emergency surgery if advanced disease and complications, usually
associated with infection and sepsis.
Cholecystostomy (operative or percutaneous)

Alternative to cholecystectomy in patients with high operative risk
Prognosis
Mortality of acute cholecystitis = 5-10%

Almost entirely confined to patients >60 with
serious associated diseases and those with
supparative complications
Complications


Infection
Cholecystoenteric fistula  results in
gallstone ileus.
Choledocholithiasis
and Cholangitis
Choledocholithiasis & Acute Cholangitis
~15% of pts with gallstones have CBD
stones (choledocholithiasis)
CD stones usually originate from GB
Less commonly 

stones form de novo in the biliary tree
International incidence rate higher b/c
primary CBD stones caused by parasites

Asians  Ascaris lumbricoides and Clonorchis sinensis
Biliary tract lithiasis most often
begins with a calculus (stone) in
the gallbladder.
A small enough calculus (or part
of a calculus) may become
impacted in the neck of the
gallbladder or cystic duct 
acute cholecystitis.
The stone may travel further down
into the common bile duct, and
impaction in this duct
(choledocholithiasis) may
produce obstruction with jaundice.
The stone may travel further down
and, near the ampulla, obstruct
the pancreatic duct, leading to
acute pancreatitis.
The stone may pass through the
ampulla and out into the
duodenum.
Symptoms and Signs
Biliary colic

From rapid  in CBD pressure due to obstructed bile
flow
Charcot’s Triad = classic cholangitis



1. RUQ pain – frequently recurring, severe, persists for several hours
2. Chills and Fever - associated with severe colic
3. Jaundice - associated with abdominal pain
Hepatomegaly – in calculous biliary obstruction
Tenderness – RUQ and epigastrium
Presentation of Choledocholithiasis
Pain = MC presenting symptom


colicky in nature, moderate in severity, and located in the RUQ
intermittent, transient, and recurrent and may be associated with nausea and vomiting.
Jaundice



CBD becomes obstructed and conjugated bilirubin enters the bloodstream.
History of clay-colored stools and tea-colored urine is obtained from such patients in
approximately 50%
The jaundice can be episodic.
Fever


Indication of cholangitis
Charcot triad: fever, jaundice, and RUQ pain strongly favors the diagnosis.
Pancreatitis



Gallstones are responsible for 50% of all cases
Conversely, 4-8% of patients with gallstones develop pancreatitis.
Pancreatitis can be precipitated if CBD obstruction occurs at the level of the ampulla of
Vater.
Primary CBD Stones
Caused by conditions leading to bile stasis and chronic bactibilia.
Up to 90% of patients with brown pigment CBD stones have (+) bile culture
results
Usually brown pigment stones. Brown stones differ from black pigment
stones by having a higher content of cholesterol. Brown stones are soft and
earthy in consistency and take the shape of the duct.
In Western populations, biliary stasis is secondary to factors such as:

sphincter of Oddi dysfunction, benign biliary strictures, sclerosing cholangitis, and
cystic dilatation of the bile ducts.
In Asian populations, A lumbricoides and C sinensis promote stasis:



Either blocking the biliary ducts or by damaging the duct walls
Results in stricture formation.
Bactibilia is also common in these instances, probably secondary to episodic portal
bacteremia.
Secondary CBD Stones
Arise from the gallbladder  migrate to the
CBD
Have a typical spectrum of cholesterol
stones and black pigment stones.
Bacteria can be cultured from the surface of
cholesterol and pigment stones but not from
the core, suggesting that bacteria do not
play a role in their formation.
Laboratory Diagnosis
 WBC  nonspecific.
 Serum and urine bilirubin - indicate obstruction of the CBD


the higher the bilirubin level, the greater the predictive value.
CBD stones are present in approximately 60% of patients with serum bilirubin
levels greater than 3 mg/dL.
 Serum amylase and lipase

acute pancreatitis complicating choledocholithiasis.
 Alkaline phosphatase and gamma-glutamyl transpeptidase


obstructive choledocholithiasis
good predictive value for the presence of CBD stones.
 Prothrombin time

In prolonged CBD obstruction, secondary to depletion of vitamin K (the
absorption of which is bile-dependent).
 Liver transaminases

choledocholithiasis complicated by cholangitis, pancreatitis, or both.
Blood culture

positive in 30-60% of patients with cholangitis.
Preoperative Diagnosis
Transabdominal ultrasonography

It is usually the first modality used in the diagnosis of patients with biliary-related symptoms.

Ultrasonography findings are accurate in the diagnosis of gallbladder stones, but CBD stones
are missed frequently (sensitivity 15-40%).

On the other hand, CBD dilatation is identified accurately, with up to 90% accuracy.
Endoscopic ultrasonography

Introduction of a high-frequency (7.5-12 MHz) ultrasonic probe advanced into the
duodenum under endoscopic guidance. A water-filled balloon is used to provide
an acoustic window.

Sensitivity and specificity of CBD stone detection are reported in range of 85100%.

Invasive, $$$, need experienced enoscopist/ultrasonographer
Computed tomography scan

very accurate in the detection of biliary tree obstruction and ductal dilatation

sensitivity of 75-90% in the detection of CBD stones = essential in evaluation of
jaundice.

Capable of defining the level of the obstruction and provides information about
the surrounding structures, especially the pancreas.
MRCP


noninvasive tool with 97% accuracy, 92% sensitivity, and 100% specificity.
$$$, inconvenience, and limitations (eg, obesity, presence of metal objects, eg,
pacemakers)
Endoscopic Ultrasound (EUS)
MRCP
Cholangiography
Criterion standard for the detection of CBD stones

Endoscopic Retrograde Cholangiopancreatography (ERCP)
The CBD is cannulated through the ampulla, contrast injected, and
films are obtained.
Experience of the endoscopist is best predictor of success, (90-95%
in expert hands)
Complications = hyperamylasemia and cholangitis.

Percutaneous Transhepatic Cholangiography (PTC)
may be the modality of choice in patients in whom ERCP is difficult

(eg, previous gastric surgery)
percutaneously and transhepatically into an intrahepatic duct, and
cholangiography is performed.
Complications
Biliary Cirrhosis:

CBD obstruction >30 days  liver damage 
cirrhosis
Hypoprothrombinemia:


Pts may bleed excessively d/t PT
Responds to 10mg parenteral vitamin K or
water soluble oral vitamin K within 24-36h.
Treatment of Choledocholithiasis
CBD stone in pt with cholelithiasis and
cholecystitis:

endoscopic papillotomy and stone extraction followed by
laparoscopic cholecystectomy.
ERCP before cholecystectomy in patients with:



Gallstones and jaundice (serum bili >2 mg/dL)
Dilated CBD (>7mm)
Stones in bile duct seen on ultrasound or CT
Primary Biliary Cirrhosis
Primary Biliary Cirrhosis
Chronic disease of liver with autoimmune destruction of intrahepatic bile
ducts and cholestasis
Insidious onset

Often detected by chance finding of Alkaline Phosphatase
Women aged 40-60
Disease is progressive and complicated by:

Steatorrhea, xanthomas, xanthelasma, osteoporosis, osteomalacia, and portal
hypertension
Associated with Sjögren’s syndrome, scleroderma, hypothyroidism, and
celiac disease
Infection with Chlamydia pneumoniae may be trigger or causative agent
Xanthoma in PBC
Clinical Findings
Many asymptomatic for years
Fatigue and pruritis
Hepatomegaly with progression
Xanthomatous lesions

In skin and tendons and around eyelids
Jaundice and signs of portal HTN (late)
Risk of osteoporosis increased
Laboratory findings in PBC
Signs of cholestasis

AlkPhos, cholesterol (HDL), later bilirubin
Anti-mitochondrial Antibodies (95%)

Directed against PDH in mitochondria
Serum IgM
Diagnosis of PBC
Based on cholestatic liver chemistries and antimitochondrial antibodies in serum combined with
characteristic histology in liver biopsy
Liver biopsy

Permits histologic staging
Stage I: Portal inflammation with granulomas
Stage II: Bile duct proliferation
Stage III: Interlobular fibrous septa
Stage IV: Cirrhosis
Biliary Fibrosis
Portal area with marked ductular proliferation and minimal inflammation in a case of chronic biliary obstruction.
Treatment of PBC
Ursodeoxycholic Acid


Preferred medical treatment
slows progression, improves long-term survival, ↓risk of esophageal varices
Symptomatic Treatment

Cholestyramine or Colestipol - for pruritis
Can aggravate steatorrha leading to vitamin A,D,K deficiency


Rifampin inconsistently beneficial
Opiod antagonists
Naloxone, naltrexone – show promise for treating pruritis

5-HT3 antagonists
Ondansetron

Calcium supplementation
Helps prevent osteomalcia
Colchicine and Methotrexate

Some benefit improving symptoms and serum levels of AP
Liver transplant

Treatment of choice for advanced disease
Prognosis of PBC
Without transplant, survival = 7-10 years once symptoms
develop
Adverse prognostic indicators:






Older age
High serum bilirubin
Edema
Low serum albumin
Prolonged PT
Variceal hemorrhage
The Mayo risk score:
R = 0.871 loge (bilirubin in mg/dL) + (–2.53) loge (albumin in g/dL) + 0.039 age in years + 2.38
loge(prothrombin time in seconds) + 0.859 (edema score of 0, 0.5, or 1)
Primary Sclerosing
Cholangitis
Primary Sclerosing Cholangitis
Uncommon disease characterized by diffuse inflammation of biliary tract  leading to
fibrosis and strictures of biliary system.
Most common in men age 20-40 and closely associated with ulcerative colitis
(present in ~2/3 of pts with PSC)


Only 1-4% of patients with UC develop PSC.
Like UC, smoking is associated with a ↓risk of PSC
Associated with HLA-B8 and DR3 or DR4
ANCA (70%), with fluorescent staining characteristics and target antigens distinct
from those in Wegener’s
In AIDS, PSC may result from infections caused by

CMV, cryptosporidium, or microsporum.
PSC is usually progressive, leading to cirrhosis, portal hypertension, and liver failure.
Symptoms and Signs
Progressive obstructive jaundice

Frequently associated with malaise, pruritus,
anorexia, and indigestion.
Complications of chronic cholestasis


Osteoporosis
Malabsorption of fat soluble vitamins
Laboratory Diagnosis of PSC
AP or GGT – MC abnormality
Serum transaminases can be normal or 
 serum bilirubin

in advanced PSC
Hepatic synthetic tests (albumin, PT, etc)

abnormal in advanced PSC
 Serum cholylglycine (bile salt)

out of proportion to the elevation of serum bilirubin.
p-ANCAs

in 60-82% of patients with PSC. (Frequency in UC is similar.)
CA 19-9

level greater than 100 U/mL has 75% sensitivity and 80% specificity in identifying PSC
patients with cholangiocarcinoma.
Imaging Diagnosis of PSC
ERCP

Cholangiography remains criterion standard
Cholangiography remains the criterion standard for
establishing the diagnosis of PSC.
irregularly distributed, multifocal strictures and dilatations of
the intrahepatic and extrahepatic bile ducts = beading
MRCP

Noninvasive, but less sensitive (90%) than
ERCP(97%) for visualizing intrahepatic ducts
Imaging of PSC
The radiographic pattern of PSC is
that of strictures of varying lengths in
the intrahepatic and extrahepatic
ducts.
There may intervening areas of
minimal dilatation of the ducts with a
resulting "beaded" appearance.
Usually there are multiple areas of
involvement. In this case almost all of
the visualized ducts are abnormal in
contour.
ERCP
ERCP image shows
multifocal strictures
and irregularity of the
right intrahepatic bile
ducts.
Treatment of PSC
No effective medical therapies exist

Ciprofloxacin
Episodes of acute bacterial cholangitis

Ursodeoxycholic acid (UDCA)
improves symptoms and LFTs in adult patients with PSC.
ERCP


Balloon dilation of localized strictures. Repeated procedures improves survival.
If major stricture – short term stent relieves symptoms and improves LFTs
Surgical resection

In patients without cirrhosis, resection of dominant bile duct stricture
may improve survival vs. ERCP because of ↓risk cholangiocarcinoma.
Prognosis of PSC
Averages 10 years once symptoms appear
Adverse prognostic markers:




Older age
Higher serum bilirubin and AST
Lower albumin levels
History of variceal bleeding
Complications:


Cholangiocarcinoma (10-15%) of adults with PSC.
Colon CA/dysplasia
In patients with ulcerative colitis, PSC is independent risk factor
Strict adherence to colonoscopic surveillance program avised
Neoplasms in the
Biliary Tract
Carcinomas of Biliary Tract
Manifestations
weight loss (77%)
nausea (60%)
anorexia (56%)
abdominal pain (56%)
fatigue (63%)
pruritus (51%)
fever (21%)
malaise (19%)
diarrhea (19%)
constipation (16%)
abdominal fullness (16%)
Symptomatic patients
usually have advanced
disease, with spread to
hilar lymph nodes before
obstructive jaundice
occurs.
It is associated with a
poor prognosis.
Carcinoma of the Gallbladder
Uncommon malignancy – 2.5/100,000
Most common of biliary tract cancers (54%)
>90% are adenocarcinomas
In Native Americans, GB carcinoma is the most commonly seen GI
malignancy
Male:Female = 1:3
Overall mean survival rate = 6 months, 5-year survival rate is 5%
At diagnosis, most of the GB is replaced or destroyed by the cancer
Risk Factors for GB Cancer

Cholelithiasis
often large and symptomatic stones present

Chronic infection of gallbladder
Salmonella Typhi



Genetic Factors
GB polyps >1cm in diameter
Mucosal calcification of GB (Porcelain GB)
carcinoma in 25%



Anomalous pancreaticobiliary ductal junction
Congenital biliary cysts
Environmental carcinogens
Anabolic Steroids
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Symptoms and Signs
Jaundice

skin or icteric sclerae
Early  Pain in RUQ with radiation into back
Anorexia, weight loss, fever and chills (cholangitis), supraclavicular LN
Courvoisier’s Law


Palpable GB with obstructive jaundice signifies malignant disease
This generalization accurate only 50% of time
Hepatomegaly

Usually present and associated with liver tenderness
Ascites

Can occur with peritoneal implants
Hematemesis or melena

From erosion of tumor into blood vessel (hemobilia)
Carcinoma of Gallbladder
Location:

fundus (60%), body (30%), neck (10%)
Notoriously insidious

Diagnosis made incidently at surgery
Spread



Early lymphatic spread  retroperitoneal, right celiac,
and pancreaticoduodenal nodes.
Direct invasion of the liver, extrahepatic biliary ducts,
and duodenum and colon (less common) occurs.
Intraperitoneal seeding may occur.
TNM Staging
Tis = Carcinoma in situ
Stage 0: Tis
N0
M0
T1a = GB wall: invades lamina propria
T1b = GB wall: invades muscle layer
Stage I: T1
N0
M0
T2 = Perimuscular connective tissue
Stage II: T2
N0
M0
Stage III: T1-2
T3
N1
N0-1
M0
M0
Stage IVA: T4
N0-1
M0
Stage IVB: T1-4
T1-4
N2
N0-2
M0
M1
T3 = Perforates serosa or directly
invades liver or adjacent organ
T4 = Invades main portal vein or hepatic
artery or multiple organs
N1a = Hepatoduodenal ligament nodes
N1b = Other regional lymph nodes
M0 = No distant metastases
M1= Distant metastases
Carcinoma of Bile Ducts
(Cholangiocarcinoma)
Tumor that arises from the intrahepatic or extrahepatic biliary epithelium
3% of all cancer deaths in the US
> 90% are adenocarcinomas, remainder are squamous cell CA
3 Geographic Locations:

Intrahepatic
Least common

Extrahepatic (ie, perihilar)
Perihilar (Klatskin tumors) = Most common


At bifurcation of R and L hepatic ducts
Distal extrahepatic
Upper border of pancreas  ampulla
The etiology of most bile duct cancers remains undetermined.
Possible Etiologies
Infections

In SE Asia, chronic infx with liver flukes
Clonorchis sinensis, Opisthorchis viverrini and Fasciola Hepatica
Inflammatory bowel disease

CCC generally develops in patients with long-standing ulcerative colitis
and PSC.
Chemical exposures
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
primarily among workers in the aircraft, rubber, and wood finishing
industries.
Thorotrast
Congenital diseases of the biliary tree

choledochal cysts and Caroli disease
Pathophysiology of CCC
Long-standing inflammation as with PSC,
chronic parasitic infection suggested to play a
role by inducing hyperplasia  cellular
proliferation  malignant transformation.
Grow slowly and infiltrate walls of the ducts,
dissecting along tissue planes
Local extension:

liver, porta hepatis, regional LN of the celiac and
pancreaticoduodenal chains.
Symptoms and Signs
Progressive jaundice




MC manifestation of bile duct cancer
The obstruction and subsequent cholestasis tends to occur early if the tumor is
located in the common bile duct or common hepatic duct.
Jaundice often occurs later in perihilar or intrahepatic tumors and is often a
marker of advanced disease.
The excess of conjugated bilirubin is associated with bilirubinuria and clay
colored stools.
Pruritus


usually is preceded by jaundice, but itching may be the initial symptom of CCC.
related to circulating bile acids.
Weight loss
Abdominal pain

common in advanced disease and often is described as a dull ache in the RUQ
Courvoisier’s Sign
If CCC located distal
to the cystic duct
takeoff 

the patient may have a
palpable gallbladder,
(Courvoisier sign)
Laboratory Examination
Biliary Neoplasms
 Conjugated Bilirubin

Total serum bilirubin from 5-30mg/dL
 Alkaline Phosphatase and GGT
 Serum Cholesterol
AST

normal or mildly elevated
CA 19-9

If elevated – may help distinguish CCC from benign biliary
stricture
Imaging in Biliary Neoplasms
Ultrasonagraphy and CT:



Show GB mass in GB Carcinoma
Intrahepatic masses or biliary duct dilation
CT also shows involved regional LN
MRI with MRCP


Visualization of biliary tree
Detection of vascular invasion
Positron Emission Tomography (PET)

Can detect CCC as small as 1cm
The most helpful diagnostic studies before surgery are
either PTC or ERCP with biopsy and cytology
Treatment of Biliary Neoplasms
Curative Surgery (Gallbladder CA)




May be attempted in young and fit pts if tumor is well localized.
5 year survival for localized (stage 1, T1a, N0, M0) is as high as 80% with laparoscopic
cholecystectomy
Only 15% if muscular invasion (T1b)
If tumor unresectable at laparotomy
Cholecystoduodenostomy or T-tube drainage of CBD
Curative Surgery (CCC)


Curable in <10%
Palliation - place self-expandable metal stent via ERCP or PTC
Photodynamic therapy – palliative
Radiotherapy

Relieve pain and contributes to biliary decomression
Chemotherapy with gemcitabine – limited response
In general, prognosis is poor, with few patients surviving >12 months after surgery
A 95 year-old woman presented with upper abdominal pain and jaundice;
ultrasound demonstrated gallstones. Symptoms were short in duration, and
jaundice began to clear rapidly. In view of her age and improving condition,
she was treated conservatively for cholecystitis. However, she then
developed protracted vomiting; endoscopy demonstrated several stones in
the duodenum.
What is the most likely cause this type of complication?
a. Malignancy extending into duodenum
b. Perforation of gallbladder
c. Caroli’s syndrome
d. Metastasis from another primary tumor
Answer
B. This stone could not be removed
endoscopically. Surgery confirmed the
suspicion that the gallbladder had
perforated into the duodenum, releasing
the stones into the duodenal lumen.
Measurement of the largest stone after
surgical removal revealed it to be over 5
cm in length (right).