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Objective: To evaluate yttrium-90 (Y90) radioembolization outcomes across Child-Pugh scores in patients with advanced hepatocellular carcinoma (HCC)., Materials and Methods: From April 2005 to December 2018, 106 consecutive patients with BCLC Stage C HCC who underwent Y90 radioembolization were retrospectively analyzed. Exclusion criteria included additional malignancy (n = 7), death unrelated to liver disease (n = 2), metastases (n = 2), or lack of follow-up data (n = 4). Ninety-one patients were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method and compared between groups with the log-rank test. Cox regression modeling was used to evaluate the prognostic factors for survival., Results: Mean age was 63 years and 85.7% were male. HCV infection was the most common etiology of liver disease (58.2%). Sixty-four (70.3%) patients were Child-Pugh A, 19 (20.9%) patients were B7, and eight (8.8%) patients were B8-9. Median OS after radioembolization was 20.2 [95% confidence interval (CI) 13.0-27.4], 6.0 (95% CI 4.4-7.6), and 5.5 (95% CI 2.5-8.5) months for Child-Pugh A, B7, and B8/9 groups, respectively (P < 0.001 for B7 vs. A; P = 0.537 for B7 vs. B8/9). The multivariable Cox regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score (P < 0.001), Child-Pugh class (P = 0.005), tumor morphology pattern (P = 0.012), and Y90 delivery location (P = 0.020) were significant independent predictors of overall survival., Conclusions: Outcomes from Y90 for BCLC C HCC for Child-Pugh B7 patients were equivalent to B8/9 patients and significantly worse compared to Child-Pugh A patients. Although further research is warranted, these results suggest continued cautious patient selection for radioembolization in advanced HCC.

Objective: To investigate the most suitable timing parameters when using sorafenib to enhance the anti-tumor effects of transarterial embolization (TAE) in a rabbit VX2 liver tumor model., Materials and Methods: Twenty-five Japanese white rabbits were randomly assigned to five equal groups two weeks after VX2 tumor transplantation to the liver. We then performed the combination treatment with sorafenib and TAE in the according ways; Group 1 (TAE just before consecutive 7-day administration of sorafenib), Group 2 (TAE on second day of the administration period), Group 3 (TAE on fourth day of the administration period), and Group 4 (TAE after the administration period). Group 5 underwent TAE only. The anti-tumor effects were assessed by the tumor growth rates and by the immunohistochemical analysis of the density of intratumoral vessels., Results: The tumor size increased by 103 ± 23% in Group 1, 126 ± 50% in Group 2, 177 ± 44% in Group 3 196 ± 78% in Group 4, and 211 ± 20% in Group 5. The difference between Group 1 and Group 5 and Group 2 and Group 5 was significant. The ratio of areas positive for CD31 in specimens was 2.06 ± 0.90% in Group 1, 1.86 ± 0.59% in Group 2, 3.51 ± 2.10% in Group 3, 3.67 ± 0.79% in Group 4, and 4.84 ± 0.81% in Group 5. The difference between Group 1 and Group 5, Group 2 and Group 5, and Group 2 and Group 4 was significant., Conclusion: We suggest that the ideal time of TAE is prior to or early after commencement of sorafenib administration.

Purpose: We investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads ® ) to be used for transarterial chemoembolization., Method: After separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loaded samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope., Results: Spectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar., Discussion: The use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.

Purpose: To evaluate the embolic effect and degradability of gelatin microspheres (GMS) using various degrees of cross-linkage and particle sizes in rabbit renal artery embolization., Methods: Four types of GMS were used, as follows: 2 types of cross-linkage and 2 types of particle size. Twenty-four rabbits (6 in each group) were used for the renal artery embolization. Renal angiography was performed before and after embolization of right renal artery. Follow-up renal angiography was performed 2 days (n = 2), 5 days (n = 2), and 15 days (n = 2) after embolization in each group, and then kidneys were removed for histopathological evaluation. Vascular areas of the angiography were measured by Image J software, and the reperfusion rate was calculated. In renal specimens, residual GMS were checked and the degree of degradation was classified according to a 4-point scale., Results: The mean amounts of large- and small-particle-size GMS injected were 15.0 and 34.3 mg, respectively. Tissue necrosis was confirmed in each group; however, no difference was observed among groups. Renal reperfusion was observed more with small GMS than with large GMS. Renal reperfusion was also observed more with low cross-linked GMS than with high cross-linked GMS. In histopathological specimens, large GMS were confirmed in lobar artery, and small GMS were confirmed in lobular artery. Low cross-linked GMS completely degraded 15 days after embolization. In contrast, high cross-linked GMS were persistent 15 days after embolization., Conclusion: Degree of cross-linkage and particle size affected degradability and reperfusion.

Purpose: This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin-lipiodol suspensions., Methods: Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration., Results: At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point after the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits., Conclusions: We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.