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©The Author(s) 2020.
World J Gastroenterol. Aug 28, 2020; 26(32): 4833-4845
Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4833
Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4833
Table 1 Baseline characteristics of enrolled patients
Total (n = 661) | Patients without extrahepatic metastasis (n = 617) | Patients with extrahepatic metastasis (n = 44) | P value | |
Age (yr) | 66.9 ± 10.20 | 66.8 ± 10.2 | 68.4 ± 9.98 | 0.301 |
Male, n (%) | 497 (75.2) | 469 (76.0) | 28 (63.6) | 0.066 |
Etiology of liver cirrhosis, n (%) | 0.084 | |||
Alcohol | 137 (20.7) | 131 (21.2) | 6 (13.6) | |
HBV | 351 (53.1) | 322 (52.2) | 29 (65.9) | |
HCV | 111 (16.8) | 108 (17.5) | 3 (6.8) | |
Combined | 40 (6.1) | 38 (6.2) | 2 (4.5) | |
Others | 22 (3.3) | 18 (2.9) | 4 (9.1) | |
Platelet (× 103/μL) | 127.8 ± 55.1 | 127 ± 54.7 | 141.2 ± 63.1 | 0.304 |
AST (IU/mL) | 49.0 ± 45.6 | 48.6 ± 43.2 | 54.7 ± 72.1 | 0.40 |
ALT (IU/mL) | 37.2 ± 46.8 | 36.7 ± 44.9 | 43.0 ± 69.2 | 0.392 |
ALP (U/L) | 97.4 ± 38.6 | 96.7 ± 38.7 | 107.4 ± 35.2 | 0.076 |
Albumin (mg/dL) | 4.3 ± 2.9 | 4.3 ± 3.0 | 3.9 ± 0.6 | 0.015 |
Total bilirubin (mg/dL) | 0.93 ± 0.83 | 0.92 ± 0.84 | 1.04 ± 0.67 | 0.378 |
Serum AFP (IU/mL) | 209.7 ± 1558.3 | 185.5 ± 1503.8 | 548.3 ± 2179.0 | 0.283 |
PIVKA-II (mAU/mL) | 331.9 ± 2901.4 | 336.3 ± 2973.6 | 246.1 ± 542.6 | 0.907 |
BCLC stage, n (%) | 0.034 | |||
0 | 257 (39.0) | 248 (40.2) | 9 (20.5) | |
A | 378 (57.1) | 345 (55.8) | 33 (75.0) | |
B | 26 (3.9) | 24 (3.9) | 2 (4.5) | |
mUICC stage, n (%) | 0.096 | |||
I | 298 (45.0) | 28 (46.0) | 13 (29.5) | |
II | 316 (47.7) | 288 (46.6) | 28 (63.6) | |
III | 48 (7.3) | 45 (7.3) | 3 (6.8) | |
Tumor size (cm) | 2.42 ± 1.02 | 2.41 ± 1.02 | 2.62 ± 1.05 | 0.18 |
Ablation size/tumor size ratio | 2.04 ± 0.97 | 2.07 ± 0.97 | 1.57 ± 0.74 | 0.001 |
Tumor number | 1.19 ± 0.45 | 1.19 ± 0.46 | 1.16 ± 0.37 | 0.356 |
Encapsulated tumor, n (%) | 157 (23.7) | 146 (24.2) | 11 (25.6) | 0.840 |
Subcapsular tumor, n (%) | 263 (39.7) | 240 (39.4) | 23 (53.5) | 0.069 |
Follow-up duration, d (median, range) | 1204 (183-5016) | 1175 (183-5016) | 1379 (187-4541) | 0.270 |
Table 2 Characteristics of patients with first recurrence following radiofrequency ablation (n = 333)
Patients without extrahepatic metastasis | Patients with extrahepatic metastasis | P value | |
AFP level | |||
Initial (median, range) | 8.13 (0.70-30000.0) | 21.750 (0.836-13148.0) | 0.291 |
1st recurrence (median, range) | 7.08 (0.93-50000.0) | 28.15 (0.73-70000.0) | 0.274 |
CTP score, n (%) | 0.044 | ||
A | 277 (95.8) | 39 (88.6) | |
B | 12 (4.2) | 5 (11.4) | |
Recurrence free survival, d (median, range) | 821 (49-3944) | 389 (79-2041) | < 0.001 |
First recurred site, n (%) | < 0.001 | ||
RFA site | 53 (18.3) | 7 (15.3) | |
Same hepatic lobe | 145 (50.2) | 20 (45.5) | |
Different hepatic lobe | 60 (20.8) | 8 (18.2) | |
Both hepatic lobe | 31 (10.7) | 1 (3.1) | |
Extrahepatic area | 0 (0.0) | 8 (18.2) | |
Peritoneum | 5 | ||
Lymph nodes | 3 | ||
mUICC stage at 1st recurrence, n (%) | < 0.001 | ||
I | 140 (48.4) | 17 (38.6) | |
II | 101 (34.9) | 13 (29.5) | |
III | 38 (13.1) | 4 (9.1) | |
IVa | 5 (1.7) | 2 (4.5) | |
IVb | 0 (0.0) | 8 (18.2) | |
Rescue Treatment modalities, n (%) | 0.003 | ||
TACE | 138 (47.7) | 15 (34.1) | |
RFA | 110 (38.2) | 13 (29.5) | |
Sorafenib | 1 (0.3) | - | |
Surgery | 8 (2.8) | 3 (6.8) | |
Radiotherapy | 1 (0.3) | 3 (6.8) | |
Liver transplantation | 1 (0.3) | - | |
TACE | 11 (3.8) | 3 (6.8) | |
RFA PEIT | 1 (0.3) | - | |
None | 9 (3.1) | 5 (11.4) | |
Follow-up loss | 9 (3.1) | 2 (4.5) |
Table 3 Clinical features of patients with extrahepatic metastasis (n = 44), n (%)
Clinical features | Value |
Location of metastasis1 | |
Lymph nodes | 16 (36.3) |
Bone | 12 (27.3) |
Lung | 13 (29.5) |
Solitary/multiple | 4 (30.7)/9 (69.2) |
Unilateral/Bilateral | 4 (30.7)/9 (69.2) |
Lower lobe/non-lower lobe/all lobes | 2 (15.4)/9 (69.2)/2 (15.4) |
Peritoneum | 12 (27.3) |
Diagnostic modality | |
Abdomen enhanced CT | 30 (68.2) |
Abdomen enhanced MRI | 3 (6.8) |
Spine MRI | 3 (6.8) |
PET-CT | 5 (11.4) |
Chest X-ray | 3 (6.8) |
Chest enhanced CT | 3 (6.8%) |
Tumor marker increment (AFP, PIVKA) | |
Both | 14 (36.8) |
Either | 17 (44.7) |
AFP/PIVKA | 15 (39.5)/2 (5.3) |
None | 7 (18.4) |
N/A | 6 |
Patients diagnosed of EHM with either of abdomen enhanced CT or serum AFP elevation (> 15 IU/mL) | 38 (86.4) |
Time to extrahepatic metastasis (years, median, range) | 2.68 (0.38-10.6) |
Intra-hepatic HCC status at diagnosis of EHM (mUICC T stage) | |
T0/T1/T2 | 19 (43.2)/5 (11.4)/7 (15.9) |
T3/T4a | 2 (4.5)/11 (25.0) |
Table 4 Univariate and multivariate analysis of factors associated with extrahepatic metastasis
Univariate analysis | Multivariate analysis | |||
OR (95%CI) | P value | OR (95%CI) | P value | |
BCLC stage (0 vs A, B) | 2.93 (1.38–6.20) | 0.003 | ||
mUICC stage (I vs II, III) | 2.04 (1.04–3.96) | 0.034 | ||
Post-RFA complication (fever, abscess) | 2.78 (1.31–5.92) | 0.050 | ||
Presence of intra-hepatic recurrence | 48.8 (6.68–356.63) | 0.000 | ||
ALP > 97 U/L | 2.29 (1.23-4.26) | 0.008 | ||
1st recurrence free survival < 2 yr | 2.88 (1.54-5.38) | 0.001 | 2.44 (1.16-5.14) | 0.019 |
Ratio of ablation zone and tumor size < 2 | 3.84 (1.76-8.39) | 0.001 | 3.33 (1.34-8.27) | 0.010 |
Presence of tumoral thrombosis | 2.57 (1.13-5.84) | 0.024 | ||
AFP > 400 IU/mL at 1st recurrence | 4.52 (2.03-10.07) | 0.000 | 3.35 (1.33-8.43) | 0.010 |
mUICC stage > 2 at 1st recurrence | 2.49 (1.22-5.06) | 0.012 |
- Citation: Yoon JH, Goo YJ, Lim CJ, Choi SK, Cho SB, Shin SS, Jun CH. Features of extrahepatic metastasis after radiofrequency ablation for hepatocellular carcinoma. World J Gastroenterol 2020; 26(32): 4833-4845
- URL: https://www.wjgnet.com/1007-9327/full/v26/i32/4833.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i32.4833