Long-Term Survival Following Hepatectomy for Hepatocellular Carcinoma

Sheung Tat FANDepartment of Surgery, The University of HongKong

Chair Professor

The 6th Chinese Conference on Oncology & 9th Cross-Strait Academic Conference on Oncology

Hepatectomy for Hepatocellular Carcinoma

Hospital mortality 5-year survival

Foster （ USA ） 1977 58% -

Lee （ HongKong ） 1982 20% 20%

Nagasue （ Japan ） 1993 7% 26.4%

Belghiti （ France ） 1994 4.7% -

Sheen （ Taiwan ） 1996 6% 22%

Improvement of prognosis after hepatectomy for hepatocellular carcinoma(1989 – 2008）

% major hepatectomy

% patients not requiring blood transfusion

% hospital death

0

10

20

30

40

50

60

70

80

90

100

year

percent

Improvement of prognosis after hepatectomy for hepatocellular carcinoma(1989 – 2008）

% major hepatectomy

% patients not requiring blood transfusion

% hospital death

0

10

20

30

40

50

60

70

80

90

100

年份

百分比

5-year survival: 36% → 49%

• Refinement of surgical skills

• Meticulous perioperative nursing care

• Intensive postoperative follow-up

Whether the efficacy of hepatetomy for hepatocellular carcinoma would be further improved?

Comparison of survival rates after hepatectomy for hepatocellular carcinoma

preoperative data 1989–1998 (n=390)

1999–2008 (n=808)

age 54 56*

Concurrent disease 27.7% 39.4%*

Indocyaninc green clearance test

11.3% 11.4%

Serum albumin 41 g/L 40 g/L*

Serum bilirubin 11µmol/L 12µmol/L*

*P<0.05

Comparison of survival rates after hepatectomy for hepatocellular carcinoma

data of surgery1989–1998

(n=390)1999–2008

(n=808)

Major hepatectomy 68.7% 57.5%*

Anterior approach for right hepatectomy

28.6% 62%*

Use of ultracision harmonic scalpel

71.5% 92.6%*

Blood loss

major hepatectomy

minor hepatectomy

1.5L

1.7L

1L

0.7L*

0.92L*

0.5L*

Abdominal drainage 85.4% 20.9%**P<0.05

Comparison of survival rates after hepatectomy for hepatocellular carcinoma

pathologic data1989–1998

(n=390)1999–2008

(n=808)

Liver cirrhosis 49.5% 60.4%*

Chronic hepatitis 36.7% 27.1%

Normal liver 13.8% 12.5%

TNM staging I

II

IIIA

IVA

5.4%

36.2%

31%

27.4%

8.7%

33.3%

33.3%

24.7%

margin 9.7% 3.7%*

*P<0.05

Comparison of survival rates after hepatectomy for hepatocellular carcinoma

postoperative data 1989–1998 (n=390)

1999–2008 (n=808)

Machanical ventilation 53% 17.2%*

ICU duration 2 days 1 day*

Hospital stay 12 days 10 days*

Rates of complication 39.2% 24.8%*

Hospital mortality

cirrhosis of the liver

chronic hepatitis

normal liver

6.2%

7.8%

4.2%

5.6%

3.1%*

3.1%*

2.3%

5

Overall recurrence 78.2% 60.2%*

*P<0.05

Long-term overall survival rate of patients with hepatocellular carcinoma treated by hepatetomy

1989 – 1998 (n=390)

1999 – 2008 (n=808)

survival rate

1-year

3-year

5-year

74.8%

54.2%

42.1%

83.3%*

64.9%*

54.8%*

*P<0.000

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Years

2220181614121086420C

umul

ativ

e su

rviv

al (

%)

100

90

80

70

60

50

40

30

20

100

1999-2008 (n=808) 1999-2008 (n=772)

Overall survival Tumor-free survival

year year

Cum

ulat

ive

surv

ival

（%）

Cu

mu

lativ

e s

urv

iva

l （

%）

1989-1998 (n=390)

1989-1998 (n=349)

P<0.0001 P=0.0024

Comparison of overall survival rates of patients with hepatocellular carcinoma treated by hepatetomy

based on TNM Staging(UICC 1997)

Years

20181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Stage I

1999-2008 (n=70)

1989-1998 (n=21)

P=0.4523

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Stage II

1999-2008 (n=269)

1989-1998 (n=141)

P=0.0032

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Stage III

1999-2008 (n=269)

1989-1998 (n=121)

P=0.0106

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Stage IV

1999-2008 (n=200)

1989-1998 (n=107)

P=0.0069

year year

yearyear

Cum

ulat

ive

surv

ival

（%）

Cum

ulat

ive

surv

ival

（%）

Cumulative survival

（%）

Cum

ulat

ive

surv

ival

（%）

Survival rates of patients treated by major hepatectomy VS. minor hepatectomy

Years

2220181614121086420C

umul

ativ

e su

rviv

al (%

)

100

90

80

70

60

50

40

30

20

100

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%)

100

90

80

70

60

50

40

30

20

100

1999-2008 (n=465)1999-2008 (n=343)

Cum

ulat

ive

surv

ival

（%）

Cu

mu

lativ

e s

urv

iva

（%）

year year

Major hepatectomy Minor hepatectomy

Overall survival Overall survival

1989-1998 (n=268) 1989-1998 (n=122)

P=0.0054 P=0.0002

Overall survival rates based on potential liver status

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)

100

90

80

70

60

50

40

30

20

100

A

1999-2008 (n=488)

1989-1998 (n=193)

1999-2008 (n=219)

1989-1998 (n=143)

1999-2008 (n=101)

1989-1998 (n=54)

cirrhosis

Chronic hepatitis

Normal liver

Cum

ulat

ive

surv

ival

(%）

Cum

ulat

ive

surv

ival

(%）

Cum

ulat

ive

surv

ival

(%）

year

year

year

P<0.0001

P=0.4566

P=0.0200

B

C

Continuous improvement of survival rates

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%)

100

90

80

70

60

50

40

30

20

100

Overall survival

Cum

ulat

ive

surv

ival

（%）

year

2004-2008 (n=426)

1999-2003 (n=382)

1994-1998 (n=241)

1989-1993 (n=149)

P<0.0001

Factors affecting survival rates

• Symptoms

• Blood loss > 2L

• Postopertive complications

• Number of tumor nodules

• Microvessel invasion

• Margin of resection

• TNM staging

Contributions of surgons to the improvement of survival rate

• Reduce blood loss

• Avoid postoperative complications

• Acquire R0 resection

Pre

-op

ICG

% (

15m

in)

80

60

40

20

0

Distribution of 15 min ICG retention rate for patients treated by hepatectomy

Liver function Child-Pugh A grade(n=1074)

Hospital death 4%

Liver function Child-Pugh B grade(n=46)

Hospital death 8.7%

P < 0.0001

Median=11.1

Median=17.4

Pre

op

era

tive

15

min

IC

G r

ete

ntio

n r

ate

Fan ST, J Hepatobiliary Pancreat Surg, 2009

範上達 , Mastery of Surgery, 2007, P. 1090

Liver congestion

Liver failure

Mortaluty

SIRS

Hyperdynamic injury to small liver remnant

Liver ischemia Massive bleeding

Sepsis

Smaller segment II/III

Invaded right hepatic vein & middle hepatic veinAnterior approach for right hepatectomy,

resection of proximal middle hepatic vein &segment IVb hepatic vein

Overall survival rates of liver cancer patients with tumor status meeting Milan Criteria after hepatectomy

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%)

100

90

80

70

60

50

40

30

20

100

1999-2008 (n=343)

Cum

ulat

ive

surv

ival

（%）

year

72.5%

1989-1998 (n=110)

P=0.0237

Predicting survival after liver transplantation for patients with liver cancer

5-year survival

Meeting Milan criteria (n=444) 73.3%

Beyond Milan criteria (n=1112) 53.6%

Mazzaferro V et al, Lancet Oncology, 2009

Comparison of survival after partial hepatectomy single tumor 5cm vs. tumor number 2 – 3, each 3cm

Years

1614121086420

Cum

ulat

ive

surv

ival

(%

)100

90

80

70

60

50

40

30

20

100

Single tumor 5cm (n=385)

tumor number 2-3, each 3cm (n=25)

P=0.0306

Cum

ulat

ive

surv

ival

（%）

year

70.2%

• Major hepatectomy

• R0 resection

• No postoperative complications

• No microvessel invasions

Associated factors with the survival of patients meeting Milan Criteria after hepatectomy

Multivariate analysis

Comparison of survival between patients treated by major hepatectomy (single tumor 5cm, negtive margin) and patients receiving living donor liver transplantation

Years

1614121086420

Cum

ulat

ive

surv

ival

(%

)100

90

80

70

60

50

40

30

20

100

living donor liver transplantation (n=36)

Partial hepatectomy (n=116)

P=0.2684

Cum

ulat

ive

surv

ival

（%）

Long-term survival after partial hepatectomy（ 1989 – 2000.5）

2220181614121086420

100

90

80

70

60

50

40

30

20

10

0

Patients survive more than 10 years (n=127)26.4%

Patients survive less than 10 years (n=354)

P<0.0001

Cum

ulat

ive

surv

ival

（%）

year

Cumulative survival rate of tumor-free patients vs. Patients with recurrence in 10 years after hepatectomy for

cancer (1989 – May 2000)

Years

2220181614121086420

Cum

ulat

ive

surv

ival

(%

)100

90

80

70

60

50

40

30

20

100

Tumor-free survive more than 10 years (n=74) 17%

Tumor-free survive less than 10 years(n=360)

P<0.0001

Cum

ula

tive

sur

viva

l（%）

year

Death reasons for patients survived more than 10 years without recurrence

Reasons Number of patients

Time after surgery

Lung recurrence 1 10.8

Bleeding of duodenal ulcer

1 13.2

MODS 1 12.5

Lung cancer 2 17.8

11.6

Summary• 5 -year TNM Staging I 81.7%

II 77.2% IIIA 44% IVA 28.2%

• For the patients with high TNM staging, the efficacy of patients comlicated with cirrhosis receiving major hepatectomy improves continuously.

• The efficacy of hepatectomy with tumor status meeting Milan Criteria is similar to liver transplantation.

• For patients with resectable liver cancer, hapetectomy still remains the first choice in areas short of corpse organs.