Combined interventional therapies of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most commonmalignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades,the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone,and play more important roles in treating unresectable HCC.

Combined transarterial chemoembolization and arterial administration of Bletilla striata in treatment of liver tumor in rats

AIM: To evaluate and compare the effect of combined transarterial chemoembolization (TACE) and arterial administration of Bletilla striata (a Chinese traditionalmedicine against liver tumor) versusTACE alone for the treatment of hepatocellular carcinoma (HCC) in ACI rats.METHODS: Subcapsular implantation of a solid Morris hepatoma 3 924A (2 mm3) in the liver was carried out in 30 male ACI rats. Tumor volume (V1) was measured by magnetic resonance imaging (MRI) on day 13 after implantation. The following different agents of interventional treatment were injected after retrograde catheterization via gastroduodenal artery (on day 14), namely, (A) TACE (0.1 mg mitomycin +0.1 mi Lipiodol) + Bletilla striata (1.0 mg) (n= 10); (B) TACE + Blebilla stnata(1.0 mg) + ligation of hepatic artery (n=10),(C) TACE alone (control group, n=10). Tumor volume (V2)was assessed by MRI (on day 13 after treatment) and the tumor growth ratio (V2/V1) was calculated.RESULTS: The mean tumor volume before (V1) and after (V2) treatment was 0.0355 cm3 and 0.2248 cm3 in group A,0.0374 cm3 and 0.0573 cm3 in group B, 0.0380 cm3 and 0.3674 cm3 in group C, respectively. The mean ratio (V2/V1)was 6.2791 in group A, 1.5324 in group B and 9.1382 in group C. Compared with the control group (group C), group B showed significant inhibition of tumor growth (P＜0.01),while group A did not (P＞0.05). None of the animals died during implantation or in the postoperative period.CONCLUSION: Combination of TACE and arterial administration of Bletilla striata plus ligation of hepatic artery is more effective than TACE alone in the treatment of HCC in rats.

Assessment of hepatocellular carcinoma vascularity before and after transcatheter arterial chemoembolization by using first pass perfusion weighted MR imaging

AIM:To assess the vascularity of hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE) with the quantitative parameters obtained by first pass perfusion weighted MR imaging (FP-MRI). METHODS:Seventeen consecutive patients with one to three lesions in liver underwent FP-MRI before treatment. FP-MRI was also performed one,three,six,nine months, and one year after TACE.The baseline signal intensity (SO) of pre-TACE and one month after TACE was analyzed,the vascularity of HCC assessed by steepest slope of the signal intensity versus time curves (SS) was blindly correlated with their DSA feature and clinical outcome. RESULT:No significant difference was found on baseline signal intensity (S0) between pre-TACE and one month after TACE (F=0.309,P=0.583),The SS (mean,32% per second) of lesion one month after TACE was lower than that of pre-TACE (mean,69% per second),but with no statistical significance (F=3.067,P=0.092).When local recurrence occurred,the time intensity curves became steeper.The vascularity of HCC before and after TACE graded by SS closely correlated with that by DSA (K=0.453,P<0.05). CONCLUSION:FP-MRI is a useful criterion for selecting effective interventional treatment for patients with HCC in their initial treatment and during follow up.

Changes of tumor microcirculation after transcatheter arterial chemoembolization:First pass perfusion MR imaging and Chinese ink casting in a rabbit model

AIM: To observe the change of tumor microcirculation after transcatheter arterial chemoembolization (TACE) with bletilla microspheres by using first pass perfusion MR imaging (FP) and Chinese ink casting.METHODS: VX2 carcinoma cells were surgically implanted into the left and right lobes of liver of 30 New Zealand white rabbits, which were divided into 3 groups at random. Emulsion of lipiodol mixed with mitomydn C, and 5-FU bletilla microspheres were injected into the hepatic artery respectively, and saline was used as control agent. MR imaging was performed with turbo-flash sequence 14 d after tumor implantation and 7 d after interventional therapy. The steepest slopes (SS) of the signal intensity versus time curves were created for quantitative analysis, 7.5% Chinese ink gelatin solution was injected through ascending artery (17 cases) or portal vein(2 cases) for lesion microvessel area (MVA) measurement after the last MRI examination.The correlation between perfusion imaging and MVA was studied blindly.RESULTS: The SS values at the rim of tumor in lipiodol group (mean, 49% per second) and bletilla group (mean,35% per second) were significantly decreased (P<0.05) as compared with control group (mean, 124% per second), no difference was found between lipiodol and bletilla groups(P>0.05). In lipiodol group, the MVAs (24 974±11 836μm^2) in the center of the tumor were significantly smaller than those of the control group (35 510±15 675 μm^2) (P<0.05),while the MVAs (80 031±22 745 μm^2) around the tumor were significantly increased because small and dense plexuses appeared around the tumor which correlated to intense reaction of granulation tissue. None of the vessels was seen in the tumor in bletilla group, the peripheral MVAs of the tumor were significantly smaller than those of the control group (P<0.05) and lipiodol group (P<0.05). There was a good correlation between SS and MVAs in control group (rsl, 0.985, P<0.0001) and bletilla group (rsl, 0.743,P<0.05), the correlation was not significant in lipiodol group(rsl, 0.527, P>0.05).CONCLUSION: TACE with bletilla microspheres may enhance its anti-tumor effect by inhibiting the angiogenesis,and FP-MRI provides useful information to assess the TACE effect by depicting tumor vascularization and perfusion,

Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats

AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.METHODS: 5'-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6)ultra-fluid lipiodol was administrated via hepatic artery.Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.CONCLUSION: ASODN can transfect Walker-256 cells.ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.