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Department of Surgery and TransplantationDepartment of Surgery and Transplantation University of BolognaUniversity of Bologna
Department of Surgery and TransplantationDepartment of Surgery and Transplantation University of BolognaUniversity of Bologna
Variable outcomes of surgical Variable outcomes of surgical treatment for intrahepatic and treatment for intrahepatic and
hilar cholangiocarcinoma?hilar cholangiocarcinoma?
Variable outcomes of surgical Variable outcomes of surgical treatment for intrahepatic and treatment for intrahepatic and
hilar cholangiocarcinoma?hilar cholangiocarcinoma?
Definition of CholangiocarcinomaDefinition of CholangiocarcinomaWeimann, Br J Surg 2000; 87:1182-87Weimann, Br J Surg 2000; 87:1182-87
Review of the international literature:Review of the international literature:
• Intrahepatic type Intrahepatic type Intrahepatic bile duct carcinomaIntrahepatic bile duct carcinoma Peripheral cholangiocarcinomaPeripheral cholangiocarcinoma Cholangiocellular carcinoma (CCC)Cholangiocellular carcinoma (CCC)
• Extrahepatic typeExtrahepatic type Biliary confluence (Klatskin’s tumor) Biliary confluence (Klatskin’s tumor) Distal bile ductDistal bile duct
Cholangiocarcinoma is the second most common malignant tumor of the liverCholangiocarcinoma is the second most common malignant tumor of the liver
Cholangiocellular CarcinomaCholangiocellular CarcinomaAetiological FactorsAetiological Factors
• Western countriesWestern countries associated only with primary sclerosingassociated only with primary sclerosing
cholangitis (PSC) in about 6-11% of cases cholangitis (PSC) in about 6-11% of cases(Chalasani, Hepatology 2000)(Chalasani, Hepatology 2000)
• Eastern countries Eastern countries (10 times more frequent)(10 times more frequent) hepatobiliary parassitosis hepatobiliary parassitosis (Chen, Dig Dis Sci 2000)(Chen, Dig Dis Sci 2000)
intrahepatic lithiasis intrahepatic lithiasis (Groen, New Eng J Med 2000)(Groen, New Eng J Med 2000) intrahepatic biliary cystsintrahepatic biliary cysts
• To evaluate any clinico-pathologic differences To evaluate any clinico-pathologic differences between intrahepatic cholangiocarcinoma and between intrahepatic cholangiocarcinoma and Klatskin’s tumor, early and long term results Klatskin’s tumor, early and long term results after surgical therapy for cholangiocarcinoma after surgical therapy for cholangiocarcinoma were retrospectively reviewed in a 15-year were retrospectively reviewed in a 15-year Single Center’s experienceSingle Center’s experience
• To evaluate any clinico-pathologic differences To evaluate any clinico-pathologic differences between intrahepatic cholangiocarcinoma and between intrahepatic cholangiocarcinoma and Klatskin’s tumor, early and long term results Klatskin’s tumor, early and long term results after surgical therapy for cholangiocarcinoma after surgical therapy for cholangiocarcinoma were retrospectively reviewed in a 15-year were retrospectively reviewed in a 15-year Single Center’s experienceSingle Center’s experience
Variable outcomes of surgical treatment for intrahepatic Variable outcomes of surgical treatment for intrahepatic and hilar cholangiocarcinoma?and hilar cholangiocarcinoma?
Variable outcomes of surgical treatment for intrahepatic Variable outcomes of surgical treatment for intrahepatic and hilar cholangiocarcinoma?and hilar cholangiocarcinoma?
HCCHCC121121
HCCHCC121121
HCC on CirrhosisHCC on Cirrhosis311311
HCC on CirrhosisHCC on Cirrhosis311311
Repeated ResectionsRepeated Resections5050
Repeated ResectionsRepeated Resections5050
MetastasesMetastases390390
MetastasesMetastases390390
Klatskin TumorKlatskin Tumor225 (2.1%)5 (2.1%)
Klatskin TumorKlatskin Tumor225 (2.1%)5 (2.1%)
TraumaTrauma2222
TraumaTrauma2222
Benign TumorsBenign Tumors151151
Benign TumorsBenign Tumors151151
OthersOthers8888
OthersOthers8888
IntrahepaticIntrahepaticcholangioca.cholangioca.
34 (2.9%)34 (2.9%)
IntrahepaticIntrahepaticcholangioca.cholangioca.
34 (2.9%)34 (2.9%)
11188188 Liver Resections Liver Resections11188188 Liver Resections Liver Resections
Liver Resections for CholangiocarcinomaLiver Resections for Cholangiocarcinoma
5959patientspatients
3434Peripheral CCPeripheral CC
2525Klatskin’s tumorKlatskin’s tumor
27 Cholangiocarcinoma27 Cholangiocarcinoma 7 mixed form 7 mixed form (Sasaki, J Surg Oncol 2001)(Sasaki, J Surg Oncol 2001)
Klatskin tumorKlatskin tumor(25 patients)(25 patients)
Peripheral CCPeripheral CC(34 patients)(34 patients)
GenderGender 14 M / 7 F14 M / 7 F 14 M / 17 F14 M / 17 F
AgeAge 58.1 58.1 ±± 10.3 10.3 62.0 62.0 ±± 9.0 9.0
DiameterDiameter 2.5 2.5 ±± 0.7 0.7 6.9 6.9 ±± 5.7 5.7
SymptomsSymptoms PainPain 5 (20.0%)5 (20.0%) 20 (58.8%)20 (58.8%)JaundiceJaundice 19 (76.0%)19 (76.0%) 2 (5.8%)2 (5.8%)NoneNone 1 (4.0%)1 (4.0%) 13 (35.4%)13 (35.4%)
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Patient CharacteristicsPatient Characteristics
Klatskin TumorKlatskin Tumor(25 patients)(25 patients)
Peripheral CCPeripheral CC(34 patients)(34 patients)
SegmentectomiesSegmentectomies -- 16 (47.1%)16 (47.1%)
Major hepatectomiesMajor hepatectomies 8 (32%)*8 (32%)* 8 (23.5%)8 (23.5%)
Extended majorExtended majorhepatectomieshepatectomies
17 (68%)*17 (68%)* 10 (29.4%)10 (29.4%)
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Operative ProceduresOperative Procedures
* In 14 cases, right portal vein embolization was applied * In 14 cases, right portal vein embolization was applied
Klatskin TumorKlatskin Tumor(25 patients)(25 patients)
Peripheral CCPeripheral CC(34 patients)(34 patients)
Postop. MorbidityPostop. Morbidity 14 (56%)14 (56%) 9 (26.4%)9 (26.4%)
Postop. MortalityPostop. Mortality 3 (12%)*3 (12%)* 1 (2.9%)*1 (2.9%)*
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Early postoperative outcomeEarly postoperative outcome
* p < 0.05* p < 0.05
44 / 5 / 599 Patients Patients ( ( 66..77 % ) % )
0
20
40
60
80
100
0 6 12 18 24 30 36 42 48 54 60
Months
%5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Overall sOverall survivalurvival
35.4%35.4%48.8%48.8%
0
20
40
60
80
100
0 6 12 18 24 30 36 42 48 54 60
Months
%
Klatskin tumor Peripheral CC
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
SSurvivalurvival by Type of Tumors by Type of Tumors
p=n.s.p=n.s.
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Resection vs palliative treatmentResection vs palliative treatment
0
25
50
75
100
0 12 24 36 48 60
%
35.4%35.4%
Palliative treat. Palliative treat. (56 (56 cases)cases) Resection Resection (59 cases)(59 cases)
p<0.01p<0.01
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Pathologic characteristicsPathologic characteristicsVascular
thrombosisPerineuralinvasion
Lymph nodemetastases
Klatskin’stumor
6 (24%) 16 (64%)* 9 (36%)
Intrahepaticcholangio-ca.
9 (26.4%) 3 (8.8%)* 10 (29.4%)
* p < 0.05* p < 0.05
•p53 mutation
•c-erbB-2
•c-met
•Muc1 expression
Biological prognostic parameters
Cholangiocellular carcinomaCholangiocellular carcinomaOverall survival depending on p27 expressionOverall survival depending on p27 expression
Fiorentino, et al. Clinic Cancer Research 2001; 7: 3994-9Fiorentino, et al. Clinic Cancer Research 2001; 7: 3994-9
0
25
50
75
100
0 12 24 36 48 60
%
p27 absentp27 absent p27 presentp27 present
p<0.001p<0.001
p27p27 present present
p27p27 absent absent
Postop.recurrencePostop.recurrence 22%22% 77.8%77.8%
Absence of Absence of recurrencerecurrence
66.7%66.7% 33.3%33.3%
5959 Liver Resections for Liver Resections for CholangiocarcinomaCholangiocarcinoma
Relation between p27 and recurrenceRelation between p27 and recurrence
p < 0.05p < 0.05
• Cholangiocarcinoma is a highly aggressive tumor Cholangiocarcinoma is a highly aggressive tumor
with a generally poor prognosis. with a generally poor prognosis.
• Liver resection is the treatment of choice leading Liver resection is the treatment of choice leading
to a 5-year survival varying from 25% to 40%.to a 5-year survival varying from 25% to 40%.
• The possibility of long-term survival depends on The possibility of long-term survival depends on
the feasibility of performing surgical resection with the feasibility of performing surgical resection with
radical intent.radical intent.
CONCLUSIONS (I)CONCLUSIONS (I)
CONCLUSIONS (II)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.