1. Does Liver Regeneration Increase the Postoperative HCC Recurrence after Curative Resection ?
Jin-Ho Lee, MD.
Department of Surgery, Yonsei University College of Medicine
Division of Hepato-Biliary-Pancreas Cancer Clinic, Institute of Gastroenterology,
Severance Hospital, Seoul, Korea

2. Background

3. P = P =0.187
In conclusion, Despite standard radiological selection criteria based on number and size, patients who underwent LDLT for HCC had more recurrence because of selection bias for other clinical characteristics.

4. Background

6. In conclusion, significant activation of cell signaling pathways leading
to tumor invasion and migration in small-for-size liver grafts promotes tumor growth and metastasis after liver transplantation.

7. Background

8. In conclusion, LDLT showed poorer outcome than DDLT
In conclusion, LDLT showed poorer outcome than DDLT. This should be considered to select optimal
strategy for HCC.

9. Study design Duration: 2006. 01. 01~2009. 12. 31 Liver volumetry
Mevisys company VoxelPlus® 2
Pre-Operative CT image
POD #7day CT image
POD #90day CT image

10. Flow diagram of Study Total patients: 420 Tumor Operation extent
Number ≤3개
Tumor size ≤5cm
Operation extent
Anatomical resection
Over Sectionectomy
Total patients: 107
Liver cirrhosis ??
Non-cirrhotic liver: 54
Cirrhotic liver: 53

11. Results Table 1. Baseline characteristics of the study population
Variable
n=107
Age
55 (27-77)
Sex (male/female)
84 (78.5%) / 23 (21.5%)
BMI (Kg/m2)
23.53 ( )
White blood cell count (103/uL)
5700 ( )
Hemoglobin (g/dL)
14.1 ( )
Platelet count (109/L)
163 (23-359)
Total protein (g/dL)
7.4 ( )
Albumin (g/dL)
4.5 ( )
AST (IU/L)
31 (12-149)
ALT (IU/L)
34 (8-158)
Total bilirubin (mg/L)
0.7 ( )
Prothrombin time (%)
Partial thromboplastin time (sec)
32.2 ( )
Alpha-feto protein (ng/mL)
28.7 ( )
PIVKA-II* (mAU/mL)
52 ( )
ICG-R15 (%)
8.9 ( )
Child-Pugh score
A (100%)
*Prothrombin induced by vitamin K absence-II

12. Results
Table 2. Perioperative and tumor characteristics of the study population
Variable
n=107
Operation extent
Rt. hemi
51 (47.7%)
Lt. hemi
27 (25.2%)
Sectionectomy
23 (21.5%)
Extended hepatecctomy
6 (5.6%)
Operation time (min)
260 ( )
Transfusion (yes/no, %)
26 (19.6%) / 81 (80.4%)
Resected liver volume (ml)
410.5 ( )
Remnent liver volume (ml)
575.5 ( )
Postoperative 90th day liver volume (ml)
851.6 ( )
Postoperative 90th day liver regeneration rate
1.384 ( )
Edmonsion-Steiner grade(I/II/III/IV/없음, %)*
4 (3.7%)/63 (58.9%)/26(24.2%)/-/14(13.2%)
Underline liver cirrhosis (yes/no, %)
53 (49.5%) / 54 (50.5%)
Tumor size (cm)
3 (1-5)
Tumor number
1 (1-3)
GVI (negative/positive, %)**
94 (87.8%) / 12 (12.2%)
MVI (negative/Positive, %)***
55 (51.4%) / 51 (48.6%)
Satellite nodule (negative/Positive, %)
98 (91.5%) / 8 (7.5%)
Intrahepatic metastasis (negative/Positive, %)
100 (93.5%) / 7 (6.5%)
Multicentric occurrence (negative/Positive, %)
98(91.5%) /9 (8.5%)
Surgical margin (negative/Positive, %)
106 (99.1%) / 1 (0.9%)
Postoperative mortality
0 (0%)
* Worst score was selected in Edmonson-Steiner grade,
** Gross vascular invasion, *** Microvascular invasion

13. Non-cirrhotic Liver

14. Clinicopathologic Outcomes
Regeneration ratio
Total
P-value
≤1.5
>1.5
(N=26)
(N=28)
(N=54)
Age (year)
53.5
(29-77) 52
(32-70)
0.386
Gender
Male 21 24 45
0.626
Female 5 4 9
AFP (ng/mL)
13.89
( )
21.68
( )
18.02
( )
0.206
PIVKAII (mAU/mL) 56
( )
56.5
( )
0.389
PLT (103/μL)
202.5
( )
205
( )
203.5
( )
0.357
INR
0.995
( )
( )
( )
Albumin (g/dL)
4.7
( )
4.6
( )
0.918
OT (IU/L) 29
(12-58)
25.5
(15-73)
(12-73)
0.343
PT (IU/L) 32
(9-87)
27.5
(8-101) 31
0.914
Bilirubin (mg/dL)
0.6
( )
0.7
( )
( )
0.708
ICG-R15 (%)
6.20%
( )
8.4
( )
7.95
0.919
OP time (min)
263.5
( )
263
( )
( )
0.789

15. Clinicopathologic Outcomes
Regeneration ratio
Total
P-value
≤1.5
>1.5
(N=26)
(N=28)
(N=54)
OP method
<0.001
Rt. hemi 2 23 25
Lt. hemi 16 18
Sectionectomy 6 1 7
Extended hepatectomy 4
Transfusion
Yes 9
0.847 No 17 19 36
Tumor No.
(1-2)
0.340
Tumor size (cm) 3
( )
( )
0.480
Satellite nodule
Absent 26 24 50
0.080
Present
Micro vascular invasion 14 15 29
0.859 11 13
Portal vein invasion 47
0.112 5
Intrahepatic meta 51
0.597
Multicentric occurrence 28 54
Resection margin R0 27 53
0.331 R1

16. Disease-free Survival: Non-cirrhotic liver
P =0.019
≤ 1.5배
> 1.5배

17. Multivariate analysis
Factor
Univariate analysis
Multivariate analysis
Patients (n)
p-value
Exp(B)
95% CI
Gender
0.228
Male 45
Female 9
Age
0.366
≤60 34
>60 20
Grade
0.169 I 2 II 28
III 18
Regeneration rate
0.019
0.047
5.252
≤1.50 26
>1.50
Satellite nodule
0.012
0.469
2.268 No 50
Yes 3
Portal vein invasion
0.602 47 6

18. Multivariate analysis
Factor
Univariate analysis
Multivariate analysis
Patients (n)
p-value
Exp(B)
95% CI
Microvascular invasion
0.032
0.325
2.102 No 29
Yes 24
Intraheaptic metastasis
0.010
0.097
7.078 51 3
AST (IU/L)
0.132
≤50
>50
ALT (IU/L)
0.024 42 12
Albumin
0.339
≤4.0 2
>4.0 52
Resection Margin
0.033
0.950
1.090 53 1
Transfusion
0.972 18 36

19. Cirrhotic liver

20. Clinicopathologic Outcomes
Regeneration ratio
Total
P-value
≤1.5
>1.5
(N=34)
(N=19)
(N=53)
Age (year)
55.0
(27-72) 55
(32-71) 56
0.914
Gender
Male 25 14 39
0.990
Female 9 5
AFP (ng/mL)
56.65
( ,84)
31.04
( )
48.52
( )
0.511
PIVKAII (mAU/mL)
( )
59.5
( ) 47
0.656
PLT (103/μL)
134
(23-255)
147
(93-278)
141
(23-278)
0.150
INR
1.035
( )
1.06
( )
1.05
( )
0.898
Albumin (g/dL)
4.15
( )
4.5
( )
4.3
( )
0.035
OT (IU/L) 37
(21-136) 30
(23-149) 35
(21-149)
0.584
PT (IU/L) 38
(12-99)
(13-158)
(12-158)
0.379
Bilirubin (mg/dL)
0.65
( )
0.7
( )
0.437
ICG-R15 (%)
11.10%
( )
8.95
( )
9.90
0.218
OP time (min)
274.0
( )
235
( )
254
0.074

21. Clinicopathologic Outcomes
Regeneration ratio
Total
P-value
≤1.5
>1.5
(N=34)
(N=19)
(N=53)
OP method
<0.001
Rt. hemi 8 18 26
Lt. hemi 1 9
Sectionectomy 16
Extended hepatectomy 2
Transfusion
Yes 7
0.135 No 27 45
Tumor No.
(1-2)
(1-3)
0.414
Tumor size (cm) 3
( )
0.568
Satellite nodule
Absent 32 48
0.237
Present 5
Micro vascular invasion 15 11
0.336 19
Portal vein invasion 31 47
0.443 6
Intrahepatic meta 33 49
0.089 4
Multicentric occurrence 29 44
0.555
Resection margin R0 34 53
0.331 R1

22. Disease-free Survival: Cirrhotic liver
P =0.040
≤ 1.5배
> 1.5배

23. Multivariate analysis
Factor
Univariate analysis
Multivariate analysis
Patients (n)
p-value
Exp(B)
95% CI
Gender
0.639
Male 39
Female 14
Age
0.717
≤60 34
>60 19
Grade
0.141 I 2 II 35
III 8
Regeneration rate
0.037
0.040
0.048
≤1.50
>1.50
Satellite nodule
0.860 No 48
Yes 5
Portal vein invasion
0.060
0.001
17.378 47 6

24. Multivariate analysis
Factor
Univariate analysis
Multivariate analysis
Patients (n)
p-value
Exp(B)
95% CI
Microvascular invasion
0.053
0.809
0.865 No 26
Yes 27
Intraheaptic metastasis
0.414 49 4
AST (IU/L)
0.007
0.005
5.464
≤50 42
>50 11
ALT (IU/L)
0.109 43 10
Albumin
0.238
≤4.0 14
>4.0 39
Resection Margin 53
Transfusion
0.020
0.137
2.055 45 8
In conclusion, among the HBV infected HCC patients with curative resection, postoperative recurrences occurred more as there were more liver regeneration in non-cirrhotic liver.
However, patients with cirrhotic liver showed the opposite result. We think this is probably because tumor recurrence will be activated more by a serial signaling pathway as there was more liver regeneration.

25. Thank you