1. 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

2. The Biliary Anatomy

3. 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
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

4. Physiology Bile Ducts Gallbladder Sphincter of Oddi
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

5. 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

6. Malignant Biliary Disease
Gallbladder Cancer
Bile Duct Cancer
Metastatic and Other Tumors

7. Gallbladder Cancer

8. 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%.

9. 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.

10. Gallbladder Cancer Risk Factors Gallstones
Calcified gallbladder (porcelain)
Biliary Salmonella typhi infection
Biliary adenomas

11. Gallbladder Cancer Symptoms Same as gallstone disease
Recurrent RUQ pain
Radiating to interscapular area
Nausea
Vomiting
Fatty food intolerance

12. 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

13. Gallbladder Cancer-TNM staging
Edge SB, et al. AJCC cancer staging handbook: from the AJCC cancer staging manual. 7th ed. New York: 2010

14. 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.

15. Gallbladder Cancer

16. 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.

17. Gallbladder Cancer

18. Gallbladder Cancer Survival
Improved survival due to an aggressive approach to gallbladder cancer comparing two time periods (TPs), and (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: , 2005.)

19. 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: , 2000.)

20. Bile Duct Cancer Definition :
Cholangiocarcinoma is an adenocarcinoma of the intrahepatic or extrahepatic bile duct.

21. Bile Duct Cancer Incidence: Etiology: 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

22. 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

23. 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

24. 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

25. Clinical Presentation
Bile Duct Cancer
Clinical Presentation
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.
Less common presenting clinical features include pruritus, fever, mild abdominal pain, fatigue, anorexia, and weight loss.
Cholangitis is not a frequent presenting finding but most commonly develops after biliary manipulation.
Except for jaundice, the physical examination is usually normal in patients with cholangiocarcinoma.

26. Classification and Staging
Bile Duct Cancer
Classification and Staging
Stage 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
Tis, carcinoma in situ; T1, tumor invades the subepithelial connective tissue; 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.

27. 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)

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

29. Bile Duct Cancer
ERCP

30. Bile Duct Cancer
MRCP
MRCP

31. Differential Diagnosis
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)

32. Bile Duct Cancer Treatment
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

33. Bile Duct Cancer

34. 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%.

35. Female, 60y, Cholangiocarcinoma
Case 1
Female, 60y, Cholangiocarcinoma
received liver resection on May 27th, 2010.
Portal Vein Reconstruction
MRCP before Operation

36. Case 2 Bismuth IIIb Portal vein invasion
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

37. Femal, 50y, hilar Cholangiocarcinoma received central hepatectomy
biliary reconstruction of Cholangiocarcinoma
Femal, 50y, hilar Cholangiocarcinoma received central hepatectomy
Bismuth IV
胆道整形后
Tumor

38. Liver Transplantation (LT) for Cholangiocarcinoma in Our Center
Male, 57y, Cholangiocarcinoma , received liver transplantation on October 25th, 2005
before LT
5 years post LT

39. 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

40. 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

41. 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.

42. THANKS