High-Intensity Focused Ultrasound in the Treatment of Experimental Liver Cancer

Abstract

High-intensity focused ultrasound (HIFU) was used to treat Morris rat hepatoma 3924A implanted in the liver. Treatment was administered with a lens-focused 4-MHz transducer that created a focused beam of 550 W/cm2 at peak intensity. One hundred twelve rats with liver tumors were divided into two groups of 56 each. Group 1 received HIFU therapy while group 2 (the control group) did not. All rats were killed immediately or 1, 3, 7, 14, 21, or 28 days after treatment. Eight rats in each group were killed at each interval for pathologic and biochemical studies. Significant inhibition of the tumor growth was seen in the HIFU-treated group, with tumor growth inhibition rates of 65.4% to 93.1% from the third to the 28th day after treatment. Ultrasound-treated tumors showed direct thermal cytotoxic necrosis and fibrosis. An additional 56 ACl rats with liver tumors were divided into four groups of 14 each. Group 1 received doxorubicin hydrochloride intraperitoneally and HIFU therapy; group 2, HIFU therapy; group 3, doxorubicin hydrochloride; and group 4 (the control group), neither HIFU nor doxorubicin hydrochloride. Significantly improved survival rates were noted in HIFU-treated animals (groups 1 and 2) compared with those of groups 3 and 4. These data suggest that HIFU may be a useful method for local treatment of hepatic tumors.

Analysis of clinical effect of high-intensity focused ultrasound on liver cancer

“…HIFU treats inner tumor without damaging outside body. Previous research on animal angiography indicated that after treating liver tumor of Morris rat using HIFU, nourishing blood vessels which diameter was less than 200 µm of irradiation zone closed, but they were normal for blood vessels which diameter was more than 200 µm [15] . Secondly, accuracy.…”

Influence of the docetaxel administration period (neoadjuvant or concomitant) in relation to HIFU treatment on the growth of Dunning tumors: results of a preliminary study

“…The mechanism mentioned to explain the synergy between the two treatments is based on the increase in intracellular penetration of the chemotherapy, thanks to the direct and indirect effects of HIFU: the direct effect concerns the area treated by HIFU (75% of the tumoral volume) where there is an increase in blood flow and in the permeability of the tumor cell membrane thus facilitating the supply and intracellular penetration of docetaxel. 8 The cavitation generated by HIFU takes place with creating a circulating fluid flow ('microstreaming') in the interstitial tissue exposed and inducing shear forces who can created gaps between endothelial cells. 11,19 The indirect effect that concerns the nontreated tumoral area (25% of the tumoral volume) might be related to the regional hyperthermia caused by the HIFU and the diffusion of the ultrasound beam.…”

“…Studies have shown that tumor cells were more sensitive to hyperthermia (from 41.5 to 43.51C) than normal cells. 8 Moreover, hyperthermia and docetaxel have a common action since hyperthermia itself favors the disorganization of the microtubular system. 20 In the group 3, chemotherapy was administered 24 h before HIFU treatment.…”

“…The concept of combining HIFU and chemotherapy dates back to the beginning of the 1990s when studies proved that in vivo, this combination was synergic and superior to treatment with HIFU alone or chemotherapy alone. [6][7][8][9] This was notably demonstrated with adriamycin on C 1300 neuroblastoma, doxorubicin and cyclophosphamide on Morris hepatoma or more recently with mitomycin on urothelial carcinoma of the urinary bladder. 10 In 2005, we demonstrated for the first time that this HIFU/chemotherapy synergic effect also exists with the combination of paclitaxel and estramustin phosphate on Dunning tumors implanted subcutaneously in Copenhagen rats.…”

“…Two concepts might explain this phenomenon: the first is the belief that HIFU acts on tumor cells that are already weakened by chemotherapy administered 24 h before treatment; 5,8 the second belief is that it is the concomitant application of HIFU and chemotherapy that allows better intracellular diffusion of the chemotherapy and therefore an accrued cytotoxicity. [6][7][8]11 To distinguish the role of these two mechanisms we developed an experimental protocol that included an arm in which chemotherapy was administered 24 h before treatment by HIFU and an arm in which chemotherapy was administered concomitantly with HIFU treatment. The chemotherapy used in our experiment was docetaxel for which the half-life is slightly longer than 90 min when administered by i.p.…”