jacques belghiti silvio balzan, fabien stenard, satoshi ogata department of...

Jacques BelghitiSilvio Balzan, Fabien Stenard, Satoshi Ogata

Department of Hepato-Pancreatico-Biliary and United Federation of Hepato-Gastroenterology and Digestive Surgery of Beaujon

Hospital, Clichy, University Paris 7. France

Mortality after Liver Resection

427 Resection of HCC: 1990 - 2003

Normal Chronic Liver

Liver Disease

Mortality 1.2% 7.7%

•Bleeding 2% 8%•Ascites 15% 45%•Jaundice 4% 12%•Infection 15% 25%•Renal failure 0% 8%•Liver Failure 0.5% 6%

Absence or insufficient liver regeneration

0 10 20 30 40

1

3

5

7

9

11

13

15

17

19

21

23

25

Post Operative Days

Early post operative deaths within 3 days•Myocardiac infarction (n = 1)•Peritonitis due to bowel necrosis (n = 2)

In-Hospital Mortality (n = 26) 3.3%Median post operative deaths

POD 16 (range 5-39)

Elective Liver Resectionn = 775 (1998 – 2002)

Liver Parenchymal Status

0 10 20 30 40

1

3

5

7

9

11

13

15

17

19

21

23

Post Operative Days

Normal (n = 5)

Disead (n = 18) 78%

Severe Infection or Renal Failure

0 10 20 30 40

1

3

5

7

9

11

13

15

17

19

21

23

Post Operative Days

Incidence: 74%Median POD: 10 (range 2-18)

Occurrence before or at POD 5: 30 ％

In Hospital Deaths (n = 26)

0 10 20 30 40

1

3

5

7

9

11

13

15

17

19

21

23

25

Post Operative Days

Early post operative deaths within 3 days•Myocardiac infarction (n = 1)•Peritonitis due to bowel necrosis (n = 2)

Median post operative deathsLink to liver FailurePOD 16 (range 5-39)

• Postoperative Liver Failure remains the most dangerous complication after Liver Resection

• Risk of Death – Insufficient absolute or functional liver parenchyma. – Impaired tolerance to infectious complications.

•Definition ?

•Prevalence ?

•Impact on postoperative mortality ?

What is Post operative Liver Failure ?

Clinical Biological- Encephalopathy - Bilirubinemia > 150 µmol/L- Jaundice - PT < 50% - - Ascites - Factor V < 50% - ICG 15 min > 20 or 15%

• Encephalopathy, ascites or coagulopathy requering specific treatment. Hemming AW et al. Ann Surg 2003,5:686-93.

• Prolonged hyperbilirubinemia, ascites,coagulopathy requering fresh-frozen plasma, and/or encephalopathy. Jarnagin WR et al. Ann Surg 2003,4:397-407.

• Bilirubinemia > 5 mg/dL (85 µmol/L), PT < 50% for 3 or more consecutive days. Imamura H. Arch Surg 2003,138:1198-1206.

• Two of Bilirubinemia >60 µmol/L, asterixis, and prothrombin time<30%. Azoulay D. Ann Surg 2000,232:665-72

Objective

Criteria of Post operative Liver Failure

predicting high mortality rate.

–Simple: quick, cheap and non invasive.

–Efficient: allowing early diagnosis and early management.

–Standardized: compare results.

FIFTY-FIFTY AT DAY FIVE CRITERIA

Child-Pugh Score

Encephalopathy absent controlled medically poorly controlled

Ascites absent controlled medically poorly controlled

Albumin (g/l) > 35 28 – 35 < 28

Serum Bilirubin (µmol/l) < 35 35 – 50 > 50

Prothrombin Time (%) > 50 40 – 50 < 40

Peri-operative risk assessment in cirrhosis:

Child-Pugh Score: Criteria of POLF

•Encephalopathy poorly controlled

•Ascites poorly controlled

•Albumin (g/l) < 28

•Serum Bilirubin (µmol/l) > 50

•Prothrombin Time (%) < 50

Post operative period

⇨ Not applicable (anesthesia)

⇨ Frequent after liver resection

⇨ Useless (post. hemodiluition)

⇨ When ?

⇨ When ?

Liver Tests after Major Hepatectomy

50

55

60

65

70

75

80

85

90

95

100

105

TPj-1 TPj1 TPj3 TPj5 TPj7 TPj9 TPj115

10

15

20

25

30

35

40

Bbj-1 Bbj1 Bbj3 Bbj5 Bbj7 Bbj9 Bbj11

40

60

80

100

120

140

160

180

200

GG

TJ-

1

GG

TJ1

GG

TJ3

GG

TJ5

GG

TJ7

GG

TJ9

GG

TJ1

1

0

50

100

150

200

250

300

350

ASTj-1 ASTj1 ASTj3 ASTj5 ASTj7 ASTj9 ASTj110

50

100

150

200

250

300

350

ALTj-1 ALTj1 ALTj3 ALTj5 ALTj7 ALTj9 ALTj11100

110

120

130

140

150

160

170

180

190

200

210

PAj-1 PAj1 PAj3 PAj5 PAj7 PAj9 PAj11

Prothrombin Time Bilirubinemia GGT

ASAT ALAT ALP

Prospective Database from 1998 – 2002

775 elective liver resection*

• Aged: 54 ± 10 years• Malignant tumors: 531 (69%)• Major resection: 464 (60%)

• Diseased Liver present: 307 (40%)– Fibrosis 237 (31%)– Cirrhosis 94 (12%)– Steatosis >30%: 107 (14%)

• In hospital mortality: (n=26) 3.3%

Postoperative Liver Tests1998 – 2002: 775 elective liver resection

30

40

50

60

70

80

90

100

110

-2 -1 0 1 2 3 4 5 6 7 8

Postoperative Day

Pro

thro

mb

in T

ime (

% o

f n

orm

al)

10

15

20

25

30

35

40

45

Seru

m T

ota

l B

ilir

ub

in (

µm

ol/

L)

In Hospital Deaths (n = 26)

0 10 20 30 40

1

3

5

7

9

11

13

15

17

19

21

23

25

Post Operative Days

Median post operative deathsLink to liver FailurePOD 16 (range 5-39)

Postoperative Morbidity vs No Complications

40

50

60

70

80

90

100

110


0

20

40

60

80

100

120


0

50

100

150

200

250

300

350

400

ASTj-1 ASTj1 ASTj3 ASTj5 ASTj7 ASTj9 ASTj1180

100

120

140

160

180

200

220

PAj-1 PAj1 PAj3 PAj5 PAj7 PAj9 PAj11

ALP

PT Bilirubinemia

ASAT

50

55

60

65

70

75

80

85

90

95

100

105


Prothrombin Time (%)

PT < 50% 1 3 5 7

Incidence 21% 16% 6% 4%

Mortality if present 10% 16% 33% 40%

absent 1.5 % 1.3 % 1.3 % 1%

5

10

15

20

25

30

35

40


Bilirubinemia

> 50 µml/L 1 3 5 7

Incidence 17% 19% 16% 11%

Mortality if present 7% 11% 15% 17%

absent 2 % 2 % 1 % 1%

30

40

50

60

70

80

90

100

110

-2 -1 0 1 2 3 4 5 6 7 8

Postoperative Day

Pro

thro

mb

in T

ime (

% o

f n

orm

al)

10

15

20

25

30

35

40

45

Seru

m T

ota

l B

ilir

ub

in (

µm

ol/

L)

Mortality day 5

PT < 50% 33%SB > 50 µml/L 15%

PT<50% and SB>50 µml/L 59%

Fifty – Fifty at day Five Criteria after Hepatectomy

59 %4 %Bil > 50 µmol/L

7 %1 %Bil < 50 µmol/L

PT <50%PT >50%DAY 5

Mortality according to PT< 50% and Bilirubinemia >50 µmol/L

25 Patients with 50-50 criteria

•14 deaths 11 Severe Morbidity

ICU : 22 days (4 – 57)

Hospital stay: 43 days (17 –

69)-Dead without 50-50 criteria at day 5 (n=7)

3 digestive bleeding with portal thrombosis 2 biliar peritonites and septicemia by candida4 severe sepsis

Conclusions

The presence at day 5 of the criteria 50 – 50 (PT< 50% and Bilirubinemia > 50 µmol/L) is an early and strong predictor (60%) of mortality

“50-50 criteria”•At day 5 the criteria 50 – 50 (PT< 50% and Bilirubinemia > 50 µmol/L) which is an early and strong predictor (60%) of mortality can be used as a criteria of Postoperative Liver Failure.

•Most importantly, this criteria which precede any clinical evidence of complication and death by a median of 5 and 10 days can be used for:

– early assessment of infection or portal thrombosis and

– to implement specific therapeutic interventions such as prophylactic antimicrobial therapy, artificial liver support or even liver transplantation.

Case75 yrs male30/03/2004 Right hemicolectomy Dukes C, 2 metastases in right liver - 12/2004 Systemic chemotherapy (Oxaliplatin+5FU+LV)10/02/2005 Right hepatectomy Labo dataAST: 43 IU/LALT: 66 IU/LGGT: 248 IU/L T-Bil: 5 µmol/LPT: 76%

10

20

30

40

50

60

70

80

-2 -1 0 1 2 3 4 5 6 7 8 9 10

Postoperative Day

Pro

thro

mb

in T

ime

(% o

f n

orm

al)

0

50

100

150

200

Ser

um

To

tal

Bil

iru

bin

(µ

mo

l/L

)

Death

MARS

PT

Bil


-Dead with 50-50 criteria at day 5 present

1 no context of liver failure12 infected ascites – portal thrombosis

pneumopathy

-Dead without 50-50 criteria at day 5

3 digestive bleeding – biliar peritonitessepticemia by candida

7 portal thrombosis – infected ascites (3)

-No dead despite 50-50 criteria present

3 transient criteria (only at day 5) – uncomplicated outcome9 100% of morbidity

USI 22 days (4 - 57)Hospitalization 43 days (17 - 69)


-Deaths without 50-50 criteria at day 5

3 digestive bleeding biliar peritonitessepticemia with candida

7 portal thrombosis infected ascites (3)

Prothrombin Time (%)

50

55

60

65

70

75

80

85

90

95

100

105


Bilirubinemia

5

10

15

20

25

30

35

40


jacques belghiti silvio balzan, fabien stenard, satoshi ogata department of...

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