The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors

Abstract

Objective

Low-frequency ultrasound (US) in combination with microbubbles (MBs) is able to inhibit the growth of VX2 rabbit liver tumors. In this study, we investigated the feasibility of using percutaneous ethanol injection (PEI) followed by low-frequency ultrasound and microbubbles (USMB) to inhibit VX2 tumor growth.

Methods

Eighteen New Zealand rabbits with hepatic VX2 tumors were divided into three groups: PEI, low-frequency ultrasound and MBs followed by PEI (USMB + PEI), and PEI followed by USMB (PEI + USMB). PEI was performed by ultrasound-guided injection of 95 % anhydrous alcohol into internal liver tumors in rabbits twice a week for 2 weeks. The US parameters were 20 kHz, 2 W/cm², 40 % duty cycle, 5 min, and once every other day for 2 weeks. Magnetic resonance imaging (MRI) was used to observe tumors before and after treatment, to examine changes in the tumors, and to measure the diameters of the tumors. All animals were followed up for 180 days after tumor implantation. Autopsy was performed at the end of the scheduled follow-up or immediately after death. Anatomically observed metastatic sites included the liver, lung, abdomen, and pelvic cavity. The survival time of all rabbits was recorded.

Results

After 4 weeks of treatment, on MRI, the tumor diameters in the PEI, USMB + PEI, and PEI + USMB groups were 8.33 ± 1.83, 19 ± 2.61, and 4.5 ± 1.22 mm, respectively. There was a significant difference in tumor size indicated by MRI in the three groups. Tumor size was smaller in the PEI + USMB group than in the PEI and USMB + PEI groups, with t = 4.54, p = 0.0062, and t = 16.38, p < .0001, respectively. The PEI + USMB group showed the fewest metastasis sites (χ ² = 11.7333, p = 0.0194) and the longest survival period (χ ² = 7.448, p = 0.0241).

Conclusion

Percutaneous ethanol injection followed by low-frequency ultrasound and microbubbles can be effective in inhibiting rabbit liver tumors and prolonging survival time.

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