Twenty-six patients (aged 40–78 years) were included in the analysis. The median age of the C-TACE group (9 men and 4 women) was 54.5 years; in the D-TACE group (11 men and 2 women), the median age was 56 years. Based on BCLC staging criteria, the all the patients were in stage C. Based on the Child-Pugh classification standard of liver function, in the C-TACE group, 9 cases were Child-Pugh class A, the other 4 cases were class B, and the mean Child-Pugh score was 6.15 ± 0.90. In the D-TACE group, 11 cases were Child-Pugh class A, the other 2 cases were class B, and the mean Child-Pugh score was 5.77 ± 0.73. No significant differences were found between the two groups (Mann-Whitney U = 64.5, p = 0.31). All patients had HCC lesions. In the C-TACE group, there were 4 cases in the left liver and 9 cases in the right liver. In the D-TACE group, there was one case in the left liver and all other cases were in the right liver. All the patients had tumor-side portal vein branch thrombus and MPVTT. Among these, 6 cases were accompanied by contralateral first level portal vein branch tumor thrombi in the C-TACE group and 4 cases were accompanied by contralateral first level portal vein branch tumor thrombi in the D-TACE group.
All the patients successfully underwent stent implantation of a radioactive seed into the portal vein followed by TACE treatment. In the C-TACE group (Fig. 1), 13 stents were implanted (diameter: 8–14 mm, length: 60–90 mm), 13 125I radioactive seeds were used (a total of 204 125I seeds, with an average of 16 per strip), and 10.6 ml of lipiodol was used in each case on average. Fifty milligrams of epirubicin were mixed with lipiodol for each case, and 15 boxes of gelatin sponges were used to enhance embolization. In the D-TACE group (Fig. 2), 13 stents were implanted (diameter: 8–14 mm, length: 40–94 mm), and 13 125 I radioactive seeds were used (a total of 181 125I seeds, with an average of 14 per stripe); 18 bottles of DC beads were used; and five boxes of gelatin sponges were used to enhance embolization. Each bottle of DC beads contained a mixture of 40 mg of epirubicin.
Intraoperative angiography of the portal vein showed that the portal vein length of the tumor thrombus was 25.3 to 95.2 mm (average: 46.6 ± 19.1 mm) in the C-TACE group and 17.6 to 65.7 mm (average: 38.8 ± 16.5 mm) in the D-TACE group. In the C-TACE group, the average pressure of the distal main portal vein was 28.3 ± 11.2 cmH2O and 23.6 ± 10.2 cmH2O before and after stent implantation, respectively, a decrease of 4.6 ± 3.0 cmH2O, but the difference before and after stent implantation was not statistically significant (U = 74.5, P = 0.62). In the D-TACE group, the average pressures were 25.2 ± 12.3 cmH2O and 20.2 ± 11.7 cmH2O, respectively, a decrease of 5.0 ± 4.4 cmH2O, which was also not statistically significant (U = 62.5, P = 0.27). The difference in the magnitude of pressure decrease between the two groups was not statistically significant (U = 74.5, P = 0.62).
The alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum total bilirubin (TBil) levels significantly increased at 3 days and 7 days after the procedures but returned to preoperative levels after 30 days (Table 1). There were no significant differences in Child-Pugh scores between the two groups before the procedures (p = 0.47) or at 3 days (p = 0.77), 7 days (p = 0.66), 14 days (p = 0.47), and 30 days (p = 0.56) after the procedures (Fig. 3).
Table 1
Liver function parameters before and 3 days, 7 days, 14 days, 30 days after interventional procedures
| | ALT (IU/L) | AST (IU/L) | TBil (µmol/L) | Child-Pugh score |
C-TACE group | pre | 48.6 ± 28.9 | 84.6 ± 43.7 | 30.6 ± 19.1 | 5.7 ± 1.3 |
3d | 100.3 ± 151.0 | 210.0 ± 356.5 | 37.6 ± 19.9 | 6.8 ± 1.9 |
7d | 132.6 ± 154.7 | 176.1 ± 135.0 | 48.5 ± 42.9 | 6.8 ± 1.0 |
14d | 90.7 ± 29.9 | 106.0 ± 58.0 | 103.6 ± 122.9 | 6.8 ± 0.7 |
30d | 34.5 ± 54.7 | 108.8 ± 56.8 | 53.3 ± 94.2 | 6.3 ± 0.9 |
D-TACE group | pre | 53.8 ± 42.8 | 93.2 ± 54.5 | 21.0 ± 7.0 | 5.3 ± 1.3 |
3d | 451.3 ± 462.8 | 590.3 ± 428.9 | 47.9 ± 26.9 | 6.7 ± 2.0 |
7d | 200.8 ± 222.6 | 116.2 ± 67.6 | 51.6 ± 27.9 | 6.6 ± 1.3 |
14d | 121.7 ± 75.7 | 127.0 ± 121.4 | 123.1 ± 165.2 | 6.5 ± 1.3 |
30d | 47.7 ± 45.1 | 117.5 ± 145.8 | 51.5 ± 77.7 | 6.0 ± 1.2 |
ALT: alanine aminotransferase; AST: aspartate aminotransferase; TBil: serum total bilirubin |
No patient in either group had serious complications such as puncture bleeding, abdominal bleeding, tumor rupture, gastrointestinal bleeding, liver abscess, or bile aneurysm. Postoperative adverse reactions included postembolization syndrome, nausea, pain, fever and fatigue, all of which significantly improved after symptomatic treatment. Two patients with myocardial damage had chest discomfort and pain within 24 hours after the procedures in the D-TACE group treated with 80 mg (mixed with 2 bottles of DC beads) and 40 mg epirubicin (mixed with 1 bottle of DC beads), respectively. No abnormal electrocardiogram findings were observed, but the serum levels of AST, lactate dehydrogenase (LDH), and N-terminal pro B-type natriuretic peptide (NT-proBNP) within 24 hours after the procedures had transient increases. After oxygen therapy, sublingual nitroglycerin and other treatments, the indicators of myocardial damage gradually decreased after 3 days.
During the follow-up, the stent patency time of the two groups was 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group, and there was no significant difference between the groups (U = 84, p > 0.99) (Fig. 4).
According to the mRECIST criteria[6], the increased enhanced tumor tissue volume in CT or MRI images was used as the basis for evaluating disease progression. The median progression-free survival times of the two groups were 42 days and 120 days, respectively—significantly longer in the D-TACE group than in the C-TACE group (p = 0.03) (Fig. 5A). By the end of the 5-year follow-up, 3 patients in the D-TACE group still survived. From the initial diagnosis, the overall survival times were 235 days and 357 days in the two groups (p = 0.02) (Fig. 5B). From the first interventional procedures, the overall survival times of the two groups were 216 days and 239 days, respectively (p = 0.047) (Fig. 5C). The difference was statistically significant: the D-TACE group was superior to the C-TACE group regarding both PFS and OS.