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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.