The First Affiliated Hospital, Zhejiang University School of Medicine

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Biliary Tumor
Xu Xiao M.D. Ph.D.
The First Affiliated Hospital, Zhejiang
University School of Medicine The Key Laboratory
of Combined Multi-Organ Transplantation Ministry
of Public Health Hangzhou, China
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The Biliary Anatomy
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Cystic Triangle
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Physiology

• Bile Ducts
• Intrahepatic biliary tract
• Extrahepatic biliary tract
• Gallbladder
• Concentrates and stores hepatic bile during the
  fasting state and delivers bile into the duodenum
  in response to a meal
• The gallbladder epithelial cell secretes at least
  two important products into the gallbladder
  lumen glycoproteins and hydrogen ions
• Sphincter of Oddi
• It creates a high-pressure zone between the bile
  duct and the duodenum
• The sphincter regulates the flow of bile and
  pancreatic juice into the duodenum, prevents the
  regurgitation of duodenal contents into the
  biliary tract

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Frequently used Assistant Examination
ERCP
CT cholangiogram shows enhanced imaging of the
biliary system comparable to MRC. Intrahepatic
and extrahepatic biliary ducts are clearly seen
in this patient.
PTCD
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Malignant Biliary Disease

• Gallbladder Cancer
• Bile Duct Cancer
• Metastatic and Other Tumors

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Gallbladder Cancer
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Gallbladder Cancer

• An aggressive malignancy that occurs
  predominantly in elderly people.
• Besides the exceptional cases detected
  incidentally at the time of cholecystectomy for
  gallstone disease, which are usually early stage,
  the prognosis for most patients is poor.
• Reported 5-year survival rates5 38.

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Gallbladder Cancer

• Incidence

• Cancer of the gallbladder is two to three times
  more common in women than men, in part because of
  the higher incidence of gallstones in women.
• More than 75 of patients with this malignancy
  are older than 65 years.
• The incidence of gallbladder cancer varies
  considerably with both ethnic background and
  geographic location.

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Risk Factors
Gallbladder Cancer

• Gallstones
• Calcified gallbladder (porcelain)
• Biliary Salmonella typhi infection
• Biliary adenomas

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Symptoms
Gallbladder Cancer

• Same as gallstone disease
• Recurrent RUQ pain
• Radiating to interscapular area
• Nausea
• Vomiting
• Fatty food intolerance

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Gallbladder Cancer-Nevein staging

• Stage I intramucosal only
• (?????????,????)
• Stage II involvement of mucosa and
  muscularis
• (????)
• Stage III involvement of all three layers
• (??????????)
• Stage IV involvement of all three layers and
  the cystic lymph node
• (????????????????)
• Stage V involvement of liver by direct
  extension or metastases, or metastases to any
  other organ
• (???????????????????)

JE Nevin, TJ Moran, S Kay, R King. Cancer, 1976
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Gallbladder Cancer-TNM staging
Edge SB, et al. AJCC cancer staging handbook
from the AJCC cancer staging manual. 7th ed. New
York 2010
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Gallbladder Cancer

• Diagnosis

• Ultrasonography is often the first diagnostic
  modality used in the evaluation of patients with
  right upper quadrant abdominal pain.
• A heterogeneous mass replacing the
  gallbladder lumen and an irregular gallbladder
  wall are common sonographic features of
  gallbladder cancer.
• CT scan usually demonstrates a mass replacing the
  gallbladder or extending into adjacent organs.
• Cholangiography also may be helpful in diagnosing
  jaundiced patients with gallbladder cancer.
• The typical cholangiographic finding in
  gallbladder cancer is a long stricture of the
  common hepatic duct.

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Gallbladder Cancer
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Gallbladder Cancer

• Management

• The appropriate operative procedure for the
  patient with localized gallbladder cancer is
  determined by the pathologic stage.
• Cancer of the gallbladder with invasion beyond
  (stages II and III) the gallbladder muscularis is
  associated with an increased incidence of
  regional lymph node metastases and should be
  managed with an extended cholecystectomy.
• This includes lymphadenectomy of the
  cystic duct, pericholedochal, portal, right
  celiac, and posterior pancreatoduodenal lymph
  nodes.
• The results of chemotherapy in the treatment of
  patients with gallbladder cancer have been quite
  poor.

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Gallbladder Cancer
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Gallbladder Cancer

• Survival

Improved survival due to an aggressive approach
to gallbladder cancer comparing two time periods
(TPs), 1990-1996 and 1996-2002 (circles) (P lt
.03).  
(From Dixon E, Vollmer CM, Sahajpal A, et al An
aggressive surgical approach leads to improved
survival in patients with gallbladder cancer A
12-year study at a North American Center. Ann
Surg 241385-394, 2005.)
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Gallbladder Cancer

• Survival

Survival following surgical resection for T2
gallbladder cancer. Patients undergoing radical
resection (triangles) are compared with patients
undergoing simple cholecystectomy (circles) .  
(From Fong Y, Jarnigan W, Blumgart LH
Gallbladder cancer Comparison of patients
presenting initially for definitive operation
with those presenting after prior noncurative
intervention. Ann Surg 232557-569, 2000.)
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Bile Duct Cancer
Definition
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Bile Duct Cancer

• Incidence
• 1.0 per 100,000 per year
• Male to female ration of 1.31
• Average age of presentation is 50-70
• Etiology
• Common features of risk factors include biliary
  stasis, bile duct stones, and infection
• Choledocal cysts, hepatolithiasis
• Other risk factors include liver flukes,
  nitrosoamines, dioxin exposure

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Bile Duct Cancer

• Pathology

• Over 95 of bile duct cancers are adenocarcinomas
• Morphologically they are divided into nodular,
  scirrhous, diffusely infiltrating, or papillary
• Anatomically they are divided into distal,
  proximal or perihilar tumors
• About 2/3 are perihilar, and are referred to as
  Klatskin tumors and broken down according to the
  Bismuth Corlette classification

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Bile Duct Cancer
Intrahepatic CCs develop in the smaller bile
duct branches inside the liver (?????)
Hilar CCs develop at the hilum (??????)
Extrahepatic CCs originate in the bile duct
along the hepato-duodenal ligament (?????)
Murad Aljiffry,, et al. World J Gastroenterol,
2009
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Bismuth Classification for Klatskin tumors
Tumor confined to the common hepatic duct
I
II
Involve the common hepatic duct bifurcation
Affect hepatic duct bifurcation and right hepatic
duct
IIIa
IIIb
Affect hepatic duct bifurcation and left hepatic
duct
Affect biliary confluence with right and left
hepatic ducts
IVa
IVa multifocal distribution
IVb
Henri Bismuth, Ann Surg, 1992
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Bile Duct Cancer

• Clinical Presentation

1. More than 90 of patients with perihilar or
   distal tumors present with jaundice. Patients
   with intrahepatic cholangiocarcinoma are rarely
   jaundiced until late in the course of the
   disease.
2. Less common presenting clinical features include
   pruritus, fever, mild abdominal pain, fatigue,
   anorexia, and weight loss.
3. Cholangitis is not a frequent presenting finding
   but most commonly develops after biliary
   manipulation.
4. Except for jaundice, the physical examination is
   usually normal in patients with
   cholangiocarcinoma.

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Bile Duct Cancer

• Classification and Staging

Stage 0 Tis N0 M0 Stage I
T1 N0 M0 Stage II T2 N0 M0
Stage III T1 or T2 N1 or N2 M0 Stage
IVA T3 Any N M0 Stage IVB Any T
Any N M1

1. Tis, carcinoma in situ T1, tumor invades the
   subepithelial connective tissue T2, tumor
   invades peri. bromuscular connective tissue T3,
   tumor invades adjacent organs.
2. N0, no regional lymph node metastases N1,
   metastasis to hepatoduodenal ligament lymph
   nodes N2, metastasis to peripancreatic,
   periduodenal, periportal, celiac, and/or superior
   mesenteric artery lymph nodes.
3. M0, no distant metastasis M1, distant metastasis

Adapted from Greene F, Page D, Fleming I, et al
(eds) AJCC Cancer Staging Manual, 7th ed. New
York, Springer-Verlag, 2010.
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Diagnosis
Bile Duct Cancer

• Tumor markers CEA, CA 19-9
• Radiographic studies Transabdominal ultrasound,
  CT, MRCP
• Cholangiography ERCP or PTC
• Endoscopic ultrasound
• PET
• Angiography (rarely used)

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Bile Duct Cancer
Computed tomography scan visualizes mass at
hepatic duct bifurcation (arrow) resulting in
bilateral biliary dilation and extensive
perihilar malignancy
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Bile Duct Cancer
ERCP
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Bile Duct Cancer
MRCP
MRCP
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Differential Diagnosis
Bile Duct Cancer

• Choledocholithiasis
• Benign bile duct strictures (usually
  postoperative),
• Sclerosing cholangitis
• Compression of the CBD (secondary to chronic
  pancreatitis or pancreatic cancer)

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Bile Duct Cancer

• Surgical excision is the only potential curative
  treatment.
• Most tumors are unresectable and may require
  surgery or stenting for palliation in jaundiced
  individuals.
• Intrahepatic tumors may be treated like HCC with
  appropriate liver resection.
• Extrahepatic tumors may be treated with a Whipple
  Procedure.

• Treatment

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Bile Duct Cancer
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Bile Duct Cancer

• Prognosis

• Unresectable disease has a survival of 5-8 months
  on average.
• The overall 5-year survival for patients with
  resectable perihilar CA is 10-30, and 40 with
  negative margins.
• The op. mortality in perihilar disease is 6-8
• Distal disease has a mildly improved prognosis
  compared with perihilar disease.
• Overall 5 year survival for resectible disease is
  30-50.

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Case 1
Female, 60y, Cholangiocarcinoma received liver
resection on May 27th, 2010.
Portal Vein Reconstruction
MRCP before Operation
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Case 2
Femal, 54y, hilar Cholangiocarcinomareceived
left hepatectomy caudate resectionportal vein
reconctruction
Bismuth IIIb
Portal vein invasion
left hepatectomy caudate resectionportal vein
reconctruction
Portal vein resection
After portal vein reconstruction
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Femal, 50y, hilar Cholangiocarcinoma received
central hepatectomy
biliary reconstruction of Cholangiocarcinoma
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Liver Transplantation (LT)for Cholangiocarcinoma
in Our Center
Male, 57y, Cholangiocarcinoma , received liver
transplantation on October 25th, 2005
before LT
5 years post LT
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LT for Cholangiocarcinoma in Our Center
Wang Xiaoping, Male, 51y, Cholangiocarcinoma,
received LT in 1999, Survival 11 years
Lin Hanbin, Male, 46y, Cholangiocarcinoma,
received LT in 2000, Survival 10 years
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LT for Cholangiocarcinoma

• LT is an emerging therapy for unresectable CC
• 5-year survival rate from 33 to 45

Sotiropoulos GC, et al.Transplant Proc
2008 Heimbach JK, et al. Semin Liver Dis 2004
Rea DJ, etal. Ann Surg 2005
Mayo protocol
5 survival is 73
Charles B. Rosen, et al. Transplant
International. 2010
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Metastatic and Other Tumors

• Hepatocellular carcinoma and liver metastases can
  cause obstructive jaundice by direct extension
  into the perihilar bile ducts.Primary and
  secondary hepatic tumors can also produce biliary
  obstruction by metastasizing to hilar or
  pericholedochal lymph nodes.Hepatocellular
  carcinoma, colorectal carcinoma, and pancreatic
  carcinoma are the most common primary sites
  associated with biliary tract obstruction from
  lymph node metastases.

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THANKS