The First Affiliated Hospital, Zhejiang University School of MedicineThe First Affiliated Hospital, Zhejiang University School of Medicine

The Key Laboratory of Combined Multi-Organ TransplantationThe Key Laboratory of Combined Multi-Organ Transplantation

Ministry of Public HealthMinistry of Public Health

Hangzhou, China Hangzhou, China

Xu Xiao Xu Xiao M.D. Ph.DM.D. Ph.D.

Biliary Tumor

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

胆囊管

肝总管

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

CT cholangiogram shows enhanced imaging of

the biliary system comparable to MRC.

Intrahepatic and extrahepatic biliary ducts are

clearly seen in this patient. PTCD

ERCP

Malignant Biliary Disease

Gallbladder Cancer

Bile Duct Cancer

Metastatic and Other Tumors

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

Gallbladder Cancer

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.

Incidence

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 metastas

es 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

Diagnosisa) 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), 1990-1996 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.) (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.)(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

Cholangiocarcinoma is an adenocarcinoma of the intrahepatic or extrahepatic bile duct.

Definition :

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

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

Pathology

Bile Duct Cancer

Intrahepatic CCs: develop in the smaller bile duct branches inside the liver (肝内胆管癌 )

Murad Aljiffry,, et al. World J Gastroenterol, 2009

Extrahepatic CCs: originate in the bile duct along the hepato-duodenal ligament (肝外胆管癌 )

Hilar CCs: develop at the hilum

(肝门部胆管癌 )

Hilar CCs: develop at the hilum

(肝门部胆管癌 )

Bismuth Classification for Klatskin tumors

Henri Bismuth, Ann Surg, 1992

II

IIII

Tumor confined to the common hepatic duct Tumor confined to the common hepatic duct

IIIaIIIa

Involve the common hepatic duct bifurcationInvolve the common hepatic duct bifurcation

IVaIVa

Affect hepatic duct bifurcation and right hepatic ductAffect hepatic duct bifurcation and right hepatic duct

IVbIVb

Affect biliary confluence with right and left hepatic ductsAffect biliary confluence with right and left hepatic ducts

IVa+ multifocal distributionIVa+ multifocal distribution

IIIbIIIbAffect hepatic duct bifurcation and left hepatic ductAffect hepatic duct bifurcation and left hepatic duct

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 I T1 N0 M0

Stage II T2 N0 M0

a) Tis, carcinoma in situ; T1, tumor invades the subepithelial connective tissue; T2, tumor invades peri. bromuscular connective tissue; T3, tumor invades adjacent organs.

b) 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.

c) 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.

Stage III T1 or T2 N1 or N2 M0

Stage IVA T3 Any N M0

Stage IVB Any T Any N M1

Stage III T1 or T2 N1 or N2 M0

Stage IVA T3 Any N M0

Stage IVB Any T Any N M1

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

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

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

Bile Duct Cancer

Bile Duct Cancer

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%.

Prognosis

Female, 60y, Cholangiocarcinoma

received liver resection on May 27th, 2010.

Portal Vein Reconstruction

MRCP before Operation

Case 1

Case 2Femal, 54y, hilar Cholangiocarcinoma

received left hepatectomy +caudate resection+portal vein reconctruction

Bismuth IIIbBismuth IIIb

Portal vein resection

Portal vein resection

After portal vein reconstruction

After portal vein reconstruction

left hepatectomy +caudate resection+portal vein

reconctruction

left hepatectomy +caudate resection+portal vein

reconctruction

Portal vein invasionPortal vein invasion

biliary reconstruction of Cholangiocarcinoma

Femal, 50y, hilar Cholangiocarcinoma received central hepatectomy

Bismuth IVBismuth IV

胆道整形后胆道整形后

Tumor

Tumor

before LT

5 years post LT

Male, 57y, Cholangiocarcinoma , received liver transplantation on October 25th, 2005

Liver Transplantation (LT)

for Cholangiocarcinoma in Our Center

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 is an emerging therapy for unresectable CC

5-year survival rate from 33% to 45%

Sotiropoulos GC, et al.Transplant Proc 2008Heimbach JK, et al. Semin Liver Dis 2004 Rea DJ, etal. Ann Surg 2005

Mayo protocolMayo protocol

Charles B. Rosen, et al. Transplant International. 2010

5 survival is 73%

5 survival is 73%

LT for Cholangiocarcinoma

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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