Transcript Gallbladder Cancer

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
The Biliary Anatomy
Cystic Triangle
胆囊三角（cystic triangle）
肝总管、肝下缘和胆囊管围的三角区
胆囊动脉、肝右动脉、胆囊淋巴结
及副右肝管在胆囊三角经过
肝总管
胆囊管
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
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
Malignant Biliary Disease
Gallbladder Cancer
Bile Duct Cancer
Metastatic and Other Tumors
Gallbladder Cancer
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 rates:5% ~38%.
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.
Gallbladder Cancer
Risk Factors
Gallstones
Calcified gallbladder (porcelain)
Biliary Salmonella typhi infection
Biliary adenomas
Gallbladder Cancer
Symptoms
 Same as gallstone disease
 Recurrent RUQ pain
a) Radiating to interscapular area
b) Nausea
c) Vomiting
d) Fatty food intolerance
Gallbladder Cancer-Nevein staging
 Stage I: intramucosal only;
(癌组织仅限于粘膜内，即原位癌)
 Stage II: involvement of mucosa and muscularis;
(侵及肌层)
 Stage III: involvement of all three layers;
(癌组织侵及胆囊壁全层)
 Stage IV: involvement of all three layers and the cystic lymph node;
(侵及胆囊壁全层合并周围淋巴结转移)
 Stage V: involvement of liver by direct extension or metastases, or
metastases to any other organ
(直接侵及肝脏或转移至其他脏器或远处转移)
JE Nevin, TJ Moran, S Kay, R King. Cancer, 1976
Gallbladder Cancer-TNM staging
Edge SB, et al. AJCC cancer staging handbook: from the AJCC cancer staging manual. 7th ed. New York: 2010
Gallbladder Cancer
Diagnosis
a) 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.
b) CT scan usually demonstrates a mass replacing the gallbladder or
extending into adjacent organs.
c) 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.
Gallbladder Cancer
Gallbladder Cancer
Management
a) The appropriate operative procedure for the patient with localized
gallbladder cancer is determined by the pathologic stage.
b) 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.
Gallbladder Cancer
Gallbladder Cancer
Survival
Improved survival due to an
aggressive
approach
to
gallbladder cancer comparing
two time periods (TPs), 19901996 and 1996-2002 (circles) (P
< .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 241:385-394, 2005.)
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 232:557-569, 2000.)
Bile Duct Cancer
Definition :
Cholangiocarcinoma is an adenocarcinoma of the intrahepatic or extrahepatic bile duct.
Bile Duct Cancer
Incidence:
1.0 per 100,000 per year
Male to female ration of 1.3:1
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
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
Bile Duct Cancer
Intrahepatic CCs: develop in the
smaller bile duct branches inside the
liver (肝内胆管癌)
Hilar CCs: develop at the hilum
(肝门部胆管癌)
Extrahepatic CCs: originate in the bile
duct along the hepato-duodenal
ligament (肝外胆管癌)
Murad Aljiffry,, et al. World J Gastroenterol, 2009
Bismuth Classification for Klatskin tumors
I
Tumor confined to the common hepatic duct
II
Involve the common hepatic duct bifurcation
IIIa Affect hepatic duct bifurcation and right hepatic duct
IIIb
Affect hepatic duct bifurcation and left hepatic duct
IVa
Affect biliary confluence with right and left hepatic ducts
IVb
IVa+ multifocal distribution
Henri Bismuth, Ann Surg, 1992
Bile Duct Cancer
Clinical Presentation
a) 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.
b) Less common presenting clinical features include pruritus, fever, mild
abdominal pain, fatigue, anorexia, and weight loss.
c) Cholangitis is not a frequent presenting finding but most commonly
develops after biliary manipulation.
d) Except for jaundice, the physical examination is usually normal in
patients with cholangiocarcinoma.
Bile Duct Cancer
Classification and Staging
Stage 0
Tis N0 M0
Stage III
T1 or T2 N1 or N2 M0
Stage I
T1 N0 M0
Stage IVA
T3 Any N M0
Stage II
T2 N0 M0
Stage IVB
Any T Any N M1
a) Tis, carcinoma in situ; T1, tumor invades the subepithelial connective tissue;
b)
c)
T2, tumor invades peri. bromuscular connective tissue; T3, tumor invades
adjacent organs.
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.
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.
Bile Duct Cancer
Diagnosis
 Tumor markers : CEA, CA 19-9
 Radiographic studies :Transabdominal ultrasound, CT,
MRCP
 Cholangiography : ERCP or PTC
 Endoscopic ultrasound
 PET
 Angiography (rarely used)
Bile Duct Cancer
Computed tomography scan visualizes
mass at hepatic duct bifurcation (arrow)
resulting in bilateral biliary dilation and
extensive perihilar malignancy
Bile Duct Cancer
ERCP
Bile Duct Cancer
MRCP
MRCP
Bile Duct Cancer
Differential Diagnosis
 Choledocholithiasis
 Benign bile duct strictures (usually postoperative),
 Sclerosing cholangitis
 Compression of the CBD (secondary to chronic pancreatitis or
pancreatic cancer)
Bile Duct Cancer
Treatment
Surgical
excision is the
potential curative treatment.
only
Most tumors are unresectable and
may require surgery or stenting for
palliation in jaundiced individuals.
Intrahepatic tumors may be treated
like HCC
resection.
with
appropriate
liver
Extrahepatic tumors may be treated
with a Whipple Procedure.
Bile Duct Cancer
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%.
Case 1
Female, 60y, Cholangiocarcinoma
received liver resection on May 27th, 2010.
Portal Vein Reconstruction
MRCP before Operation
Case 2
Femal, 54y, hilar Cholangiocarcinoma
received left hepatectomy +caudate resection+portal vein reconctruction
Bismuth IIIb
Portal vein invasion
left hepatectomy +caudate
resection+portal vein
reconctruction
Portal vein
resection
After portal vein
reconstruction
biliary reconstruction of Cholangiocarcinoma
Femal, 50y, hilar Cholangiocarcinoma received central hepatectomy
Tum
or
胆道整形后
Bismuth IV
Liver Transplantation (LT)
for Cholangiocarcinoma in Our Center
Male, 57y, Cholangiocarcinoma , received
liver transplantation on October 25th,
2005
before LT
5 years post LT
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
LT for Cholangiocarcinoma
 LT is an emerging therapy for unresectable CC
 5-year survival rate from 33% to 45%
Mayo protocol
Sotiropoulos GC, et al.Transplant Proc 2008
Heimbach JK, et al. Semin Liver Dis 2004
Rea DJ, etal. Ann Surg 2005
5 survival is
73%
Charles B. Rosen, et al. Transplant International. 2010
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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