Kim J, Joo DJ, Hwang S, Lee JM, Ryu JH, Nah YW, Kim DS, Kim DJ, You YK, Yu HC. Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study. World J Gastrointest Surg 2023; 15(7): 1340-1353 [PMID: 37555110 DOI: 10.4240/wjgs.v15.i7.1340]
Corresponding Author of This Article
Jongman Kim, MD, PhD, Professor, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea. jongman94@hanmail.net
Research Domain of This Article
Transplantation
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Surg. Jul 27, 2023; 15(7): 1340-1353 Published online Jul 27, 2023. doi: 10.4240/wjgs.v15.i7.1340
Table 1 Baseline characteristics
Before PSM
After PSM
HCC (n = 141)
cHCC-CC (n = 111)
P value
HCC (n = 70)
cHCC-CC (n = 70)
P value
Donor
Sex (male)
89 (63.1)
69 (62.2)
0.896
47 (67.1)
45 (64.3)
0.859
Age (yr)
30 (16-68)
32 (11-60)
0.217
27 (16-63)
33 (11-58)
0.048
Body mass index (kg/m2)
23.1 (17.3-36.3)
23.0 (17.6-35.7)
0.679
23.3 (17.3-36.3)
23.5 (18.1-32.9)
0.839
Recipient
Sex (male)
127 (90.1)
95 (85.6)
0.329
65 (92.9)
60 (85.7)
0.274
Age (yr)
56 (37-70)
54 (31-66)
0.027
55 (37-60)
57 (31-66)
0.125
Body mass index (kg/m2)
24.3 (17.3-36.7)
24.0 (18.7-35.0)
0.35
23.9 (18.3-34.6)
24.1 (18.7-35.0)
0.94
Underlying liver disease
0.639
0.223
HBV
123 (87.2)
91 (82.0)
63 (90.0)
56 (80.0)
HCV
6 (4.3)
5 (4.5)
2 (2.9)
2 (2.9)
NBNC
6 (4.3)
8 (7.2)
1 (1.4)
6 (8.6)
Alcoholic
6 (4.3)
7 (6.3)
4 (5.7)
6 (8.6)
Diabetes
27 (19.1)
25 (22.5)
0.534
13 (18.6)
16 (22.9)
0.677
Hypertension
17 (12.1)
14 (12.6)
0.894
6 (8.6)
7 (10.0)
0.771
Child-Pugh class
0.613
0.914
A
66 (46.8)
46 (40.5)
30 (42.9)
30 (42.9)
B
44 (31.2)
43 (38.7)
24 (34.3)
25 (35.7)
C
31 (22.0)
23 (20.7)
16 (22.9)
15 (21.4)
MELD
10 (6-35)
11 (6-40)
0.455
11 (6-33)
11 (6-40)
0.82
WBC (/mL)
3300 (1050-16120)
3500 (1100-14300)
0.15
3325 (1050-16120)
3510 (1100-10700)
0.098
Hemoglobin (g/dL)
12.4 (6.0-16.7)
11.7 (5.9-16.4)
0.026
12.2 (7.3-15.5)
11.9 (7.0-15.9)
0.461
Platelets (1000/mL)
72000 (16000-233000)
43000 (26000-223000)
< 0.001
64500 (21000-233000)
42000 (26000-200000)
< 0.001
INR
1.20 (093-5.21)
1.25 (0.90-5.98)
0.183
1.21 (0.94-3.68)
1.23 (0.90-5.98)
0.91
Albumin (g/dL)
3.7 (2.4-4.8)
3.1 (1.8-4.7)
< 0.001
3.7 (2.4-4.8)
3.4 (1.8-4.7)
0.032
Total bilirubin (mg/dL)
1.2 (0.3-32.9)
1.5 (0.3-42.1)
0.078
1.3 (0.4-32.9)
1.4 (0.3-42.1)
0.778
AST (U/L)
37 (16-229)
42 (10-1387)
0.063
38 (16-192)
44 (10-1387)
0.137
ALT (U/L)
28 (7-205)
28 (6-1249)
0.437
26 (7-205)
29 (6-1249)
0.626
ALP (U/L)
90 (29-891)
102 (30-653)
0.013
100 (29-486)
98 (30-653)
0.423
Creatinine (mg/dL)
0.82 (0.44-1.75)
0.77 (0.20-4.58)
0.049
0.82 (0.57-1.38)
0.76 (0.20-4.58)
0.03
Table 2 Pretransplant treatments, n (%)
Before PSM
After PSM
HCC (n = 141)
cHCC-CC (n = 111)
P value
HCC (n = 70)
cHCC-CC (n = 70)
P value
Locoregional therapy prior to LT
112 (79.4)
74 (66.7)
0.03
50 (71.4)
52 (74.3)
0.849
TACE
102 (72.3)
65 (58.6)
0.023
45 (64.3)
46 (65.7)
0.859
Liver resection
24 (17.0)
20 (18.0)
0.868
10 (14.3)
14 (20.0)
0.502
RFA
46 (32.6)
17 (15.3)
0.002
17 (24.3)
12 (17.1)
0.404
Radiation therapy
13 (9.2)
8 (7.2)
0.65
6 (8.6)
6 (8.6)
0.618
Number of locoregional therapies before LT > 3
56 (39.7)
34 (30.6)
0.147
27 (38.6)
26 (37.1)
0.862
AFP > 20 ng/mL
37 (26.2)
56 (50.5)
< 0.001
23 (32.9)
25 (35.7)
0.859
PIVKA-II > 40 mAU/mL
50 (35.5)
40 (39.2)
0.591
30 (42.9)
19 (30.2)
0.152
Table 3 Perioperative and pathologic characteristics
Before PSM
After PSM
HCC (n = 141)
cHCC-CC (n = 111)
P value
HCC (n = 70)
cHCC-CC (n = 70)
P value
Perioperative
Operation (LDLT)
141 (100)
95 (85.6)
< 0.001
70 (100)
57 (44.9)
< 0.001
ABO-incompatibility
35 (24.8)
8 (7.2)
< 0.001
17 (24.3)
7 (10.0)
0.042
Macro-steatosis (%)
5 (0-20)
3 (0-30)
< 0.001
5 (1-20)
5 (0-30)
0.062
Micro-steatosis (%)
5 (1-70)
1 (0-90)
< 0.001
5 (1-40)
3 (0-90)
< 0.001
GRWR (%)
1.00 (0.65-1.71)
1.11 (0.67-3.89)
0.001
0.94 (0.67-1.70)
1.15 (0.67-3.89)
< 0.001
Cold ischemic time (min)
89 (45-168)
97 (30-1414)
0.029
95 (47-144)
97 (30-1414)
0.185
Warm ischemic time (min)
37 (16-81)
44 (20-90)
< 0.001
37 (17-81)
45 (22-87)
0.002
Operation time (min)
550 (336-960)
664 (270-1265)
< 0.001
544 (336-838)
639 (270-1265)
0.006
Hospitalization stay (d)
25 (17-445)
23 (4-262)
0.008
25 (17-94)
24 (4-262)
0.321
In-hospital mortality
2 (1.4)
4 (3.6)
0.41
1 (1.4)
4 (5.7)
0.366
Pathology
Tumor size > 3 cm
34 (24.3)
43 (38.7)
0.019
26 (37.1)
22 (31.4)
0.593
Tumor number > 3
22 (15.6)
28 (25.2)
0.079
13 (18.6)
20 (28.6)
0.232
Beyond Milan criteria
47 (33.3)
45 (40.5)
0.292
29 (41.4)
28 (40.0)
0.863
Tumor grade 3 or 4
19 (13.5)
33 (29.7)
0.002
10 (14.3)
14 (20.0)
0.502
Encapsulation
36 (25.5)
31 (27.9)
0.67
17 (24.3)
18 (25.7)
0.895
Tumor necrosis
55 (39.0)
55 (49.5)
0.098
24 (34.3)
38 (54.3)
0.027
Microvascular invasion
57 (40.4)
32 (28.8)
0.064
33 (47.1)
15 (21.4)
0.002
PVTT
7 (5.0)
15 (13.5)
0.023
4 (5.7)
7 (10.0)
0.532
BDTT
3 (2.1)
3 (2.7)
0.766
3 (4.3)
2 (2.9)
0.649
Intrahepatic metastasis
34 (24.1)
19 (17.1)
0.213
20 (28.6)
13 (18.6)
0.232
Multicentric occurrence
34 (24.1)
27 (24.3)
0.969
19 (27.1)
16 (22.9)
0.697
Lymph node metastasis
0 (0)
3 (2.7)
0.084
0 (0)
1 (1.4)
0.316
Table 4 Risk factors for tumor recurrence and death in the combined hepatocellular carcinoma and cholangiocarcinoma group
Tumor recurrence
Death
OR
95%CI
P value
OR
95%CI
P value
Univariate
Univariate
Sex (male)
4.763
1.155-19.640
0.031
Sex (male)
6.464
0.883-47.317
0.066
Recipient age
0.999
0.958-1.041
0.957
Recipient age
1.005
0.957-1.057
0.833
Locoregional therapy before LT
1.724
0.907-3.274
0.096
Locoregional therapy before LT
1.924
0.891-4.153
0.096
TACE before LT
1.826
0.989-3.371
0.054
TACE before LT
2.188
1.039-4.609
0.039
Liver resection before LT
2.594
1.387-4.852
0.003
Liver resection before LT
0.941
0.365-2.428
0.9
RFA before LT
1.616
0.781-3.340
0.196
RFA before LT
2.284
1.025-5.090
0.043
Radiation therapy before LT
0.718
0.174-2.962
0.646
Radiation therapy before LT
0.654
0.089-4.813
0.677
Number of locoregional therapies before LT > 3
1.068
1.002-1.138
0.043
Number of locoregional therapies before LT > 3
1.733
0.865-3.473
0.121
MELD
0.993
0.950-1.038
0.742
MELD
1.012
0.965-1.063
0.617
Type of LT (DDLT)
0.934
0.397-2.198
0.875
Type of LT (DDLT)
1.518
0.626-3.680
0.365
ABO-incompatibility
1.563
0.618-3.952
0.345
ABO-incompatibility
0.79
0.189-3.297
0.746
Tumor size > 3cm
3.013
1.707-5.317
< 0.001
Tumor size > 3 cm
3.462
1.740-6.888
< 0.001
Tumor number > 3
1.35
0.723-2.520
0.346
Tumor number > 3
1.463
0.694-3.084
0.318
Milan criteria (beyond)
2.495
1.403-4.436
0.002
Milan criteria (beyond)
2.813
1.395-5.670
0.004
Tumor grade 3 or 4
1.465
0.809-2.651
0.208
Tumor grade 3 or 4
1.229
0.586-2.580
0.585
Microvascular invasion
2.417
1.360-4.297
0.003
Microvascular invasion
2.28
1.153-4.507
0.018
PVTT
1.416
0.661-3.032
0.37
PVTT
1.302
0.502-3.376
0.587
BDTT
0.047
0.000-36.844
0.368
BDTT
0.048
0.000-333.805
0.5
Intrahepatic metastasis
1.357
0.676-2.722
0.39
Intrahepatic metastasis
1.182
0.515-2.716
0.693
Multicentric occurrence
1.148
0.607-2.170
0.671
Multicentric occurrence
1.125
0.526-2.403
0.762
Encapsulation
1.269
0.582-2.766
0.549
Encapsulation
0.952
0.367-2.471
0.92
Tumor necrosis
2.361
1.302-4.281
0.005
Tumor necrosis
3.22
1.531-6.773
0.002
Dominant type (CC)
0.995
0.495-2.003
0.989
Dominant type (CC)
0.823
0.375-1.805
0.627
Lymph node metastasis
13.954
3.065-63.526
0.001
Lymph node metastasis
24.719
4.683-130.472
< 0.001
AFP > 20 ng/mL
1.563
0.880-2.777
0.128
AFP > 20 ng/mL
1.527
0.769-3.033
0.226
PIVKA-II > 40 mAU/mL
1.067
0.576-1.975
0.837
PIVKA-II > 40 mAU/mL
1.762
0.865-3.589
0.118
Multivariate
Multivariate
Number of locoregional therapies before LT > 3
1.813
1.012-3.248
0.046
Tumor size > 3 cm
4.591
1.851-11.390
0.001
Tumor size > 3 cm
2.378
1.321-4.280
0.004
Lymph node metastasis
8.585
1.822-40.453
0.007
Table 5 Risk factors for tumor recurrence and death after propensity score matching
Tumor recurrence
Death
OR
95%CI
P value
OR
95%CI
P value
Univariate
Univariate
Group (cHCC-CC)
2.15
1.162-3.977
0.015
Group (cHCC-CC)
2.134
1.142-3.987
0.018
Sex (male)
2.467
0.597-10.199
0.212
Sex (male)
1.536
0.475-4.964
0.474
Recipient age
0.973
0.928-1.021
0.266
Recipient age
1.009
0.962-1.057
0.725
Locoregional therapy before LT
1.78
0.855-3.706
0.123
Locoregional therapy before LT
2.304
1.026-5.171
0.043
Number of locoregional therapies before LT > 3
2.185
1.207-3.957
0.01
Number of locoregional therapies before LT > 3
1.241
0.683-2.254
0.478
MELD
0.944
0.889-1.002
0.056
MELD
0.993
0.947-1.041
0.758
Type of LT (DDLT)
0.771
0.239-2.493
0.664
Type of LT (DDLT)
1.999
0.891-4.488
0.093
ABO-incompatibility
1.094
0.526-2.277
0.81
ABO-incompatibility
0.439
0.157-1.228
0.117
Tumor size > 3 cm
2.541
1.406-4.592
0.002
Tumor size > 3 cm
2.426
1.341-4.386
0.003
Tumor number > 3
1.81
0.957-3.422
0.068
Tumor number > 3
1.458
0.749-2.839
0.267
Milan criteria (beyond)
2.893
1.573-5.322
0.001
Milan criteria (beyond)
2.261
1.242-4.119
0.008
Tumor grade 3 or 4
1.247
0.599-2.596
0.554
Tumor grade 3 or 4
1.268
0.610-2.639
0.525
Microvascular invasion
1.936
1.068-3.510
0.03
Microvascular invasion
1.873
1.032-3.400
0.039
PVTT
1.389
0.497-3.885
0.531
PVTT
1.836
0.722-4.669
0.202
BDTT
0.595
0.082-4.322
0.608
BDTT
2.035
0.487-8.504
0.33
Intrahepatic metastasis
2.192
1.172-4.101
0.014
Intrahepatic metastasis
1.742
0.923-3.289
0.087
Multicentric occurrence
1.313
0.687-2.512
0.41
Multicentric occurrence
0.967
0.489-1.915
0.924
Encapsulation
1.447
0.701-2.986
0.317
Encapsulation
1.305
0.626-2.723
0.478
Tumor necrosis
2.245
1.229-4.101
0.009
Tumor necrosis
2.56
1.383-4.740
0.003
AFP > 20 ng/mL
1.053
0.569-1.946
0.87
AFP > 20 ng/mL
1.333
0.733-2.425
0.346
PIVKA-II > 40 mAU/mL
1.202
0.639-2.263
0.568
PIVKA-II > 40 mAU/mL
1.422
0.762-2.651
0.268
Multivariate
Multivariate
Group (cHCC-CC)
2.531
1.191-5.376
0.016
Group (cHCC-CC)
2.281
1.057-4.922
0.036
Microvascular invasion
3.232
1.486-7.029
0.003
Tumor size > 3 cm
1.343
1.123-1.605
0.001
Number of locoregional therapies before LT > 3
2.33
1.235-4.396
0.009
Tumor number > 3
1.032
1.004-1.061
0.026
Citation: Kim J, Joo DJ, Hwang S, Lee JM, Ryu JH, Nah YW, Kim DS, Kim DJ, You YK, Yu HC. Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study. World J Gastrointest Surg 2023; 15(7): 1340-1353