Wang W, Deng ZF, Wang JL, Zhang L, Bao L, Xu BH, Zhu H, Guo Y, Wen Z. Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma. World J Gastrointest Surg 2022; 14(9): 1008-1025 [PMID: 36185571 DOI: 10.4240/wjgs.v14.i9.1008]
Corresponding Author of This Article
Zhang Wen, MD, PhD, Chief Doctor, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. wenzgxmu@163.com
Research Domain of This Article
Immunology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
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World J Gastrointest Surg. Sep 27, 2022; 14(9): 1008-1025 Published online Sep 27, 2022. doi: 10.4240/wjgs.v14.i9.1008
Table 1 Propensity score matching results of associating liver partition and portal vein ligation for staged hepatectomy group and right hemi-hepatectomy group
Variable
Before matching
After matching
ALPPS (15 cases)
Hepatectomy (46 cases)
P valve
ALPPS (15 cases)
Hepatectomy (15 cases)
P valve
Age (yr)
45.1 ± 11.4
49.4 ± 9.6
0.157
45.1 ± 11.4
49.5 ± 9.9
0.276
Sex (%)
0.795
0.543
Female
2 (13.3%)
5 (10.9%)
2 (13.3%)
1 (6.7%)
Male
13 (86.7%)
41 (89.1%)
13 (86.7%)
14 (93.3%)
BMI
22.4 ± 3.2
22.8 ± 3.1
0.644
22.4 ± 3.2
23.0 ± 3.4
0.608
HCC end-stage score
5.8 ± 2.3
5.4 ± 2.6
0.626
5.8 ± 2.3
6.1 ± 3.7
0.815
BCLC stage
0.775
0.915
A
3 (20.0%)
13 (28.3%)
3 (20.0%)
3 (20.0%)
B
5 (33.3%)
12 (26.0%)
5 (33.3%)
4 (26.7%)
C
7 (46.7%)
21 (45.7%)
7 (46.7%)
8 (53.3%)
AFP (%)
0.031
1.000
≥ 400 ng/mL
11 (73.3%)
19 (41.3%)
11 (73.3%)
11 (73.3%)
< 400ng/mL
4 (26.7%)
27 (58.7%)
4 (26.7%)
4 (26.7%)
Child-Pugh class (%)
0.984
1.000
A
14 (93.3%)
43 (93.5%)
14 (93.3%)
14 (93.3%)
B
1 (6.7%)
3 (6.5%)
1 (6.7%)
1 (6.7%)
Tumor number (%)
0.125
1.000
1
10 (66.7%)
39 (84.8%)
10 (66.7%)
10 (66.67%)
> 1
5 (33.3%)
7 (15.2%)
5 (33.3%)
5 (33.33%)
Tumor size (cm)
10.7 ± 4.5
7.7 ± 4.8
0.033
10.7 ± 4.5
9.0 ± 4.9
0.332
Vascular invasion (%)
0.952
0.705
Yes
6 (40.0%)
18 (39.1%)
6 (40.0%)
5 (33.3%)
No
9 (60.0%)
28 (60.9%)
9 (60.0%)
10 (66.6%)
Extrahepatic metastasis (%)
1.000
1.000
Yes
0 (0%)
1 (2.2%)
0 (0%)
0 (0%)
No
15 (100%)
45 (97.8%)
15 (100%)
15 (100%)
Table 2 Intraoperative and postoperative conditions of patients in associating liver partition and portal vein ligation for staged hepatectomy group and right hemi-hepatectomy group
Classification of postoperative liver failure, ISGLS (A/B/C)
4/10/1
4/9/2
6/8/1
90 d survival after operation (death/alive)
0/15
1/14
1/14
Table 3 Comparison of positive expression rates of tumor-infiltrating lymphocyte subpopulations in tumor tissues in stage-I associating liver partition and portal vein ligation for staged hepatectomy, stage-II associating liver partition and portal vein ligation for staged hepatectomy, and right hemi-hepatectomy groups
ALPPS
Hepatectomy
Variance analysis
Stage-I ALPPS
Stage-II ALPPS
F valve
P valve
Total T cells (%)
3.3 ± 2.9
3.1 ± 2.0
2.8 ± 1.8
0.188
0.829
CD4+ T cells (%)
1.0 ± 0.9
1.2 ± 1.1
0.9 ± 0.5
0.458
0.635
CD8+ T cells (%)
0.8 ± 0.7
1.0 ± 0.9
0.6 ± 0.4
0.546
0.583
Treg cells (‰)
0.2 ± 0.1
0.2 ± 0.2
0.3 ± 0.1
0.166
0.848
B cells (%)
1.7 ± 1.3
1.3 ± 0.7
2.1 ± 0.8
0.726
0.490
NK cells (%)
0.7 ± 0.2
0.4 ± 0.2
0.7 ± 0.2
0.664
0.520
Table 4 Comparison of positive expression rates of tumor-infiltrating lymphocyte subpopulations in adjacent tissues in stage-I associating liver partition and portal vein ligation for staged hepatectomy, stage-II associating liver partition and portal vein ligation for staged hepatectomy, and right hemi-hepatectomy groups
ALPPS
Variance analysis
Stage-I ALPPS
Stage-II ALPPS
Hepatectomy
F valve
P valve
Total T cells (%)
2.0 ± 0.6
1.9 ± 0.9
1.8 ± 1.3
0.129
0.879
CD4+ T cells (%)
0.8 ± 0.3
0.9 ± 0.3
0.9 ± 0.7
0.258
0.774
CD8+ T cells (%)
0.8 ± 0.3
1.0 ± 0.5
1.0 ± 0.7
0.510
0.604
Treg cells (‰)
0.0 ± 0.1
0.0 ± 0.0
0.0 ± 0.0
0.292
0.748
B cells (%)
2.0 ± 1.2
1.8 ± 0.8
1.7 ± 0.5
0.269
0.765
NK cells (%)
0.7 ± 0.7
0.6 ± 0.5
0.8 ± 0.7
0.550
0.581
Table 5 Comparison of tumor-infiltrating lymphocyte subpopulations between tumor and adjacent tissues in associating liver partition and portal vein ligation for staged hepatectomy group
Stage-I ALPPS
Stage-II ALPPS
Tumor
Adjacent
P valve
Tumor
Adjacent
P valve
Total T cells (%)
3.3 ± 2.9
2.0 ± 0.6
0.116
3.1 ± 2.0
1.9 ± 0.9
0.056
CD4+ T cells (%)
1.0 ± 0.9
0.8 ± 0.3
0.403
1.2 ± 1.1
0.9 ± 0.3
0.278
CD8+ T cells (%)
0.8 ± 0.7
0.8 ± 0.3
0.902
1.0 ± 0.9
1.0 ± 0.5
0.792
Treg cells (‰)
0.2 ± 0.1
0.0 ± 0.1
0.056
0.2 ± 0.2
0.0 ± 0.0
0.156
B cells (%)
1.7 ± 1.3
2.0 ± 1.2
0.515
1.3 ± 0.7
1.8 ± 0.8
0.085
NK cells (%)
0.7 ± 0.2
0.7 ± 0.7
0.985
0.4 ± 0.2
0.6 ± 0.5
0.403
Table 6 Comparison of tumor-infiltrating lymphocyte subpopulations between tumor and adjacent tissues in right hemi-hepatectomy group
Right hemi-hepatectomy
Tumor tissues
Adjacent tissues
P valve
Total T cells (%)
2.8 ± 1.8
1.8 ± 1.3
0.105
CD4+ T cells (%)
0.9 ± 0.5
0.9 ± 0.7
0.840
CD8+ T cells (%)
0.6 ± 0.4
1.0 ± 0.7
0.101
Treg cells (‰)
0.3 ± 0.1
0.0 ± 0.0
0.043
B cells (%)
2.1 ± 0.8
1.7 ± 0.5
0.645
NK cells (%)
0.7 ± 0.2
0.8 ± 0.7
0.678
Table 7 Comparison of immunological data during stage-I associating liver partition and portal vein ligation for staged hepatectomy
Item
Preoperative
Stage-I ALPPS
F value
P value
POD1
POD3
POD5
POD7
T lymphocyte count (cells/μL)
1331.5 ± 600.0
472.8 ± 289.9
682.0 ± 346.9
837.9 ± 383.6
1012.5 ± 444.2
10.095
0.001
Total T lymphocyte percentage (%)
67.8 ± 8.7
59.6 ± 8.5
68.4 ± 12.3
70.5 ± 11.7
68.9 ± 10.3
6.717
0.000
CD4+ T lymphocytes (cells/μL)
806.3 ± 428.2
241.1 ± 202.2
412.3 ± 224.7
520.1 ± 255.1
608.0 ± 266.1
9.049
0.002
CD8+ T lymphocyte (cells/μL)
438.2 ± 194.2
187.6 ± 96.6
238.9 ± 141.0
277.4 ± 143.5
361.2 ± 201.6
11.294
0.001
Natural killer cells (%)
16.5 ± 7.8
27.2 ± 8.6
10.8 ± 6.9
11.0 ± 3.7
11.2 ± 3.7
17.341
0.000
IgA (g/L)
3.11 ± 1.28
2.63 ± 1.64
1.87 ± 0.77
2.08 ± 0.79
2.69 ± 1.24
10.025
0.001
IgG (g/L)
15.11 ± 3.70
10.52 ± 2.89
8.70 ± 2.72
8.89 ± 2.69
9.82 ± 2.70
62.360
0.000
IgM (g/L)
1.27 ± 0.68
0.89 ± 0.40
0.71 ± 0.39
0.82 ± 0.38
1.08 ± 0.53
6.114
0.008
Complement C1q (mg/L)
194.5 ± 28.7
168.9 ± 44.2
140.4 ± 39.6
157.7 ± 45.9
159.17 ± 55.3
6.726
0.000
Complement C3 (g/L)
1.18 ± 0.19
0.87 ± 0.15
0.79 ± 0.19
0.87 ± 0.21
0.91 ± 0.26
44.808
0.000
Complement C4 (g/L)
0.40 ± 0.18
0.26 ± 0.12
0.23 ± 0.11
0.25 ± 0.12
0.28 ± 0.15
8.731
0.002
Interleukin-6 (g/L)
10.7 ± 17.0
177.4 ± 121.6
84.0 ± 62.3
52.6 ± 40.9
41.2 ± 35.1
7.877
0.003
CD19 expression rate (%)
10.5 ± 4.0
9.6 ± 5.62
12.1 ± 5.6
12.7 ± 5.2
13.3 ± 6.1
1.866
0.129
Table 8 Comparison of immunological data during stage-II associating liver partition and portal vein ligation for staged hepatectomy
Item
Preoperative
Stage-II ALPPS
F value
P value
POD1
POD3
POD5
POD7
T lymphocyte count (cells/μL)
1414.4 ± 634.0
455.9 ± 255.4
716.3 ± 311.3
796.3 ± 282.8
913.4 ± 387.1
17.626
0.000
Total T lymphocyte percentage (%)
67.8 ± 8.7
63.7 ± 9.2
72.3 ± 7.5
74.8 ± 6.4
73.6 ± 7.2
8.288
0.000
CD4+ T lymphocytes (cells/μL)
806.3 ± 428.2
246.4 ± 168.2
375.9 ± 170.1
493.9 ± 196.7
537.9 ± 231.3
7.925
0.003
CD8+ T lymphocytes (cells/μL)
438.2 ± 194.2
168.5 ± 89.4
290.3 ± 184.7
291.9 ± 159.0
356.1 ± 210.8
8.775
0.000
Natural killer cells (%)
16.5 ± 7.8
23.0 ± 7.1
12.7 ± 4.6
8.7 ± 4.8
10.2 ± 3.2
15.615
0.000
IgA (g/L)
3.11 ± 1.28
2.37 ± 1.88
2.31 ± 1.41
2.59 ± 1.30
3.40 ± 1.66
8.900
0.002
IgG (g/L)
15.11 ± 3.70
8.71 ± 2.10
8.11 ± 1.90
8.53 ± 1.66
9.68 ± 2.26
12.604
0.000
IgM (g/L)
1.27 ± 0.68
0.70 ± 0.37
0.67 ± 0.28
0.70 ± 0.36
0.83 ± 0.37
1.277
0.001
Complement C1q (mg/L)
194.5 ± 28.7
140.8 ± 33.8
111.1 ± 39.1
118.5 ± 41.3
124.2 ± 42.1
14.422
0.000
Complement C3 (g/L)
1.18 ± 0.19
0.72 ± 0.27
0.54 ± 0.20
0.58 ± 0.20
0.62 ± 0.18
24.345
0.000
Complement C4 (g/L)
0.40 ± 0.18
0.22 ± 0.16
0.15 ± 0.12
0.15 ± 0.14
0.17 ± 0.16
15.305
0.000
Interleukin-6 (pg/mL)
10.7 ± 17.0
210.3 ± 160.9
62.6 ± 27.6
37.1 ± 19.7
41.6 ± 61.3
12.206
0.000
CD19 expression rate (%)
10.5 ± 4.0
9.4 ± 5.1
10.2 ± 4.1
11.2 ± 5.8
11.0 ± 5.6
0.522
0.720
Table 9 Comparison of immunological data during conventional hepatectomy
Item
Preoperative
Conventional hepatectomy
F value
P value
POD1
POD3
POD5
POD7
T lymphocyte count (cells/μL)
1194.7 ± 305.4
447.1 ± 240.9
808.8 ± 313.7
835.7 ± 323.7
1032.7 ± 323.6
123.342
0.000
Total T lymphocyte percentage (%)
71.2 ± 5.2
58.9 ± 14.5
65.9 ± 11.7
72.3 ± 9.1
72.8 ± 7.7
17.676
0.000
CD4+ T lymphocytes (cells/μL)
761.1 ± 146.6
244.1 ± 113.9
515.9 ± 155.1
520.7 ± 168.7
644.8 ± 149.1
198.675
0.000
CD8+T lymphocytes (cells/μL)
379.9 ± 119.0
147.9 ± 98.5
226.8 ± 104.5
253.0 ± 110.4
331.8 ± 120.9
106.219
0.000
Natural killer cells (%)
17.9 ± 4.7
25.8 ± 8.4
14.1 ± 3.0
12.9 ± 4.6
13.8 ± 3.8
12.893
0.000
IgA (g/L)
2.67 ± 1.49
2.23 ± 1.34
2.11 ± 1.32
2.44 ± 1.50
2.82 ± 1.60
19.117
0.000
IgG (g/L)
11.78 ± 5.58
8.14 ± 3.97
7.89 ± 3.98
8.09 ± 4.05
8.55 ± 3.95
35.249
0.000
IgM (g/L)
0.91 ± 0.39
0.54 ± 0.31
0.63 ± 0.26
0.66 ± 0.27
0.82 ± 0.30
24.051
0.000
Complement C1q (mg/L)
174.6 ± 51.3
142.8 ± 49.9
121.9 ± 46.9
125.1 ± 52.1
132.2 ± 47.0
39.750
0.000
Complement C3 (g/L)
1.11 ± 0.45
0.84 ± 0.41
0.74 ± 0.37
0.70 ± 0.36
0.73 ± 0.37
31.517
0.000
Complement C4 (g/L)
0.32 ± 0.13
0.24 ± 0.11
0.21 ± 0.11
0.22 ± 0.11
0.24 ± 0.12
37.071
0.000
Interleukin-6 (pg/mL)
16.3 ± 17.7
171.6 ± 119.2
73.3 ± 46.3
43.5 ± 28.8
44.1 ± 31.1
8.981
0.002
CD19 expression rate (%)
13.04 ± 2.21
9.93 ± 3.05
10.68 ± 3.40
12.81 ± 4.37
14.03 ± 3.62
11.115
0.000
Citation: Wang W, Deng ZF, Wang JL, Zhang L, Bao L, Xu BH, Zhu H, Guo Y, Wen Z. Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma. World J Gastrointest Surg 2022; 14(9): 1008-1025