1. Variable outcomes of surgical
treatment for intrahepatic and
hilar cholangiocarcinoma?
Department of Surgery and Transplantation
Department of Surgery and Transplantation
University of Bologna
University of Bologna

2. Definition of Cholangiocarcinoma
Weimann, Br J Surg 2000; 87:1182-87
Review of the international literature:
• Intrahepatic type
 Intrahepatic bile duct carcinoma
 Peripheral cholangiocarcinoma
 Cholangiocellular carcinoma (CCC)
• Extrahepatic type
 Biliary confluence (Klatskin’s tumor)
 Distal bile duct
Cholangiocarcinoma is the second most common malignant tumor of the liver
Cholangiocarcinoma is the second most common malignant tumor of the liver

3. Cholangiocellular Carcinoma
Aetiological Factors
• Western countries
 associated only with primary sclerosing
cholangitis (PSC) in about 6-11% of cases
(Chalasani, Hepatology 2000)
• Eastern countries (10 times more frequent)
 hepatobiliary parassitosis (Chen, Dig Dis Sci 2000)
 intrahepatic lithiasis (Groen, New Eng J Med 2000) 
intrahepatic biliary cysts

4. Variable outcomes of surgical treatment for intrahepatic
and hilar cholangiocarcinoma?
• To evaluate any clinico-pathologic differences
between intrahepatic cholangiocarcinoma and
Klatskin’s tumor, early and long term results
after surgical therapy for cholangiocarcinoma
were retrospectively reviewed in a 15-year
Single Center’s experience

5. 1188 Liver Resections
1188 Liver Resections
Others
Others HCC
HCC
Trauma
Trauma 88
88 121
121
22
22
Benign Tumors
Benign Tumors
151
151 HCC on Cirrhosis
HCC on Cirrhosis
311
311
Intrahepatic
Intrahepatic
cholangioca.
cholangioca.
34 (2.9%)
34 (2.9%)
Repeated Resections
Repeated Resections
50 Klatskin Tumor
Klatskin Tumor
50
25 (2.1%)
25 (2.1%)
Metastases
Metastases
390
390

6. Liver Resections for Cholangiocarcinoma
59
patients
34 25
Peripheral CC Klatskin’s tumor
27 Cholangiocarcinoma
7 mixed form (Sasaki, J Surg Oncol 2001)

7. 59 Liver Resections for Cholangiocarcinoma
Patient Characteristics
Klatskin tumor Peripheral CC
(25 patients) (34 patients)
Gender 14 M / 7 F 14 M / 17 F
Age 58.1 ± 10.3 62.0 ± 9.0
Diameter 2.5 ± 0.7 6.9 ± 5.7
Symptoms Pain 5 (20.0%) 20 (58.8%)
Jaundice 19 (76.0%) 2 (5.8%)
None 1 (4.0%) 13 (35.4%)

8. 59 Liver Resections for Cholangiocarcinoma
Operative Procedures
Klatskin Tumor Peripheral CC
(25 patients) (34 patients)
Segmentectomies - 16 (47.1%)
Major hepatectomies 8 (32%)* 8 (23.5%)
Extended major 17 (68%)* 10 (29.4%)
hepatectomies
* In 14 cases, right portal vein embolization was applied

14. 59 Liver Resections for Cholangiocarcinoma
Early postoperative outcome
Klatskin Tumor Peripheral CC
(25 patients) (34 patients)
Postop. Morbidity 14 (56%) 9 (26.4%)
Postop. Mortality 3 (12%)* 1 (2.9%)*
4 / 59 Patients ( 6.7 % )
* p < 0.05

15. 59 Liver Resections for Cholangiocarcinoma
Overall survival
100
80
60 48.8%
%
35.4%
40
20
0
0 6 12 18 24 30 36 42 48 54 60
Months

16. 59 Liver Resections for Cholangiocarcinoma
Survival by Type of Tumors
100
80
p=n.s.
60
%
40
20
Klatskin tumor Peripheral CC
0
0 6 12 18 24 30 36 42 48 54 60
Months

17. 59 Liver Resections for Cholangiocarcinoma
Resection vs palliative treatment
100
75
p<0.01
% 50
35.4%
25
 Palliative treat. (56
cases)
0  Resection (59 cases)
0 12 24 36 48 60

18. 59 Liver Resections for Cholangiocarcinoma
Pathologic characteristics
Vascular Perineural Lymph node
thrombosis invasion metastases
Klatskin’s 6 (24%) 16 (64%)* 9 (36%)
tumor
Intrahepatic 9 (26.4%) 3 (8.8%)* 10 (29.4%)
cholangio-ca.
* p < 0.05

19. Biological prognostic parameters
•p53 mutation
•c-erbB-2
•c-met
•Muc1 expression

20. Cholangiocellular carcinoma
Overall survival depending on p27 expression
Fiorentino, et al. Clinic Cancer Research 2001; 7: 3994-9
100
75
p<0.001
% 50
25
 p27 absent
 p27 present
0
0 12 24 36 48 60

21. 59 Liver Resections for Cholangiocarcinoma
Relation between p27 and recurrence
p27 p27
present absent
Postop.recurrence 22% 77.8%
p < 0.05
Absence of 66.7% 33.3%
recurrence

22. CONCLUSIONS (I)
• Cholangiocarcinoma is a highly aggressive tumor
with a generally poor prognosis.
• Liver resection is the treatment of choice leading
to a 5-year survival varying from 25% to 40%.
• The possibility of long-term survival depends on
the feasibility of performing surgical resection with
radical intent.

23. CONCLUSIONS (II)
• In case of Klatskin's tumor curative procedures can be
achieved by extended hepatectomies. Preoperative
portal vein embolization may reduce the rate of
postoperative morbidity and mortality.
• ICC has a lower biological aggressiveness and needs
a minor resection.
• Evaluation by molecular biology of new prognostic
factors may significantly influence therapeutic
strategies in these patients and it could also be useful
for planning adjuvant therapies during follow-up.