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Impact of focused ultrasound on the ethanol ablation of VX2 liver tumours in rabbits

  • Ultrasound
  • Published:
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Abstract

Objectives

In this study, a treatment combining ethanol ablation (EA) and focused ultrasound (FUS) was performed to investigate its synergistic ablation effect on normal liver and VX2 liver tumours in rabbits.

Methods

A total of 59 healthy New Zealand white rabbits were included. For normal liver ablation, 39 animals were treated with FUS alone (n = 12), EA alone (n = 12), EA+FUS combination treatment (n = 12), or the control treatment (n = 3). The other 20 rabbits with implanted VX2 liver tumours were treated with EA alone (n = 10) or EA+FUS (n = 10). For FUS, the liver was exposed to 1 MHz FUS with an intensity of 33.0 W/cm2 (ISPTA) for 20 s. The EA group received an injection of absolute ethanol in the liver or liver tumours. For EA+FUS combination therapy, FUS was focused at the EA injection site, and both methods were carried out at the same time.

Results

In normal liver tissues, the ablated volume treated by FUS combined with EA (1.46 ± 0.30 cm3) was approximately 3 times larger than that of EA alone (0.51 ± 0.17 cm3); in VX2 liver tumours, the tumour necrosis rate of the combination therapy was 90.27%, which was much higher than that of EA treatment (63.55%).

Conclusion

The combination of EA and FUS could effectively increase the liver ablation volume and induce more complete tumour necrosis.

Key Points

• This study demonstrated a novel method for enhancing ethanol ablation and elucidated its potential to enhance percutaneous ethanol ablation (PEA) in a simple non-invasive way.

• Ethanol excited by focused ultrasound (FUS) exposure tended to accumulate at the injection site, which could prevent ethanol from being washed out by the bloodstream.

• The combination of EA and FUS could effectively increase the liver ablation volume and induce more complete tumour necrosis.

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Abbreviations

2-D:

Two-dimensional

ALT:

Alanine aminotransferase

ANOVA:

Analysis of variance

AST:

Aspartate aminotransferase

CEUS:

Contrast-enhanced US

FUS:

Focused ultrasound

H&E:

Haematoxylin and eosin

HCC:

Hepatocellular carcinoma

HIFU:

High-intensity focused ultrasound

MEUS:

Microbubble-enhanced ultrasound

MWA:

Microwave ablation

PEA:

Percutaneous ethanol ablation

RFA:

Radiofrequency ablation

References

  1. Livraghi T, Festi D, Monti F, Salmi A, Vettori C (1986) US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 161:309–312

    Article  CAS  Google Scholar 

  2. Ebara M, Okabe S, Kita K et al (2005) Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation. J Hepatol 43:458–464

    Article  CAS  Google Scholar 

  3. Willatt JM, Francis IR, Novelli PM, Vellody R, Pandya A, Krishnamurthy VN (2012) Interventional therapies for hepatocellular carcinoma. Cancer Imaging 12:79–88

    Article  Google Scholar 

  4. Yu J, Liang P, Yu XL et al (2015) Local tumour progression after ultrasound-guided microwave ablation of liver malignancies: risk factors analysis of 2529 tumours. Eur Radiol 25:1119–1126

    Article  Google Scholar 

  5. Lencioni R, Llovet JM (2005) Percutaneous ethanol injection for hepatocellular carcinoma: alive or dead? J Hepatol 43:377–380

    Article  Google Scholar 

  6. Zhang F, Wu G, Sun H et al (2014) Radiofrequency ablation of hepatocellular carcinoma in elderly patients fitting the Milan criteria: a single centre with 13 years experience. Int J Hyperthermia 30:471–479

    Article  Google Scholar 

  7. Kirikoshi H, Saito S, Yoneda M et al (2009) Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma. Hepatol Res 39:553–562

  8. Gao W, Qiao L, Gao Y et al (2016) Effect of microbubble-enhanced ultrasound on percutaneous ethanol ablation of rat walker-256 tumour. Eur Radiol 26:3017–3025

    Article  Google Scholar 

  9. Wang S, Zhuang L, Meng Z (2013) Hepatocellular carcinoma more than 3 cm in diameter: a systematic review of transcatheter arterial chemoembolization plus percutaneous ethanol injection versus transcatheter arterial chemoembolization alone. ISRN Gastroenterol 2013:526024

    Article  Google Scholar 

  10. Hoang NH, Murad HY, Ratnayaka SH, Chen C, Khismatullin DB (2014) Synergistic ablation of liver tissue and liver cancer cells with high-intensity focused ultrasound and ethanol. Ultrasound Med Biol 40:1869–1881

    Article  Google Scholar 

  11. Oosterhof GO, Cornel EB, Smits GA, Debruyne FM, Schalken JA (1997) Influence of high-intensity focused ultrasound on the development of metastases. Eur Urol 32:91–95

    Article  CAS  Google Scholar 

  12. Rabkin BA, Zderic V, Vaezy S (2005) Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation. Ultrasound Med Biol 31:947–956

    Article  Google Scholar 

  13. Zhou Y, Gao XW (2016) Effect of hydrodynamic cavitation in the tissue erosion by pulsed high-intensity focused ultrasound (pHIFU). Phys Med Biol 61:6651–6667

    Article  CAS  Google Scholar 

  14. Coussios CC, Farny CH, Haar GT, Roy RA (2007) Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU). Int J Hyperthermia 23:105–120

    Article  CAS  Google Scholar 

  15. Carling U, Barkhatov L, Reims HM et al (2019) Can we ablate liver lesions close to large portal and hepatic veins with MR-guided HIFU? An experimental study in a porcine model. Eur Radiol 29:5013–5021

    Article  Google Scholar 

  16. Napoli A, Anzidei M, Marincola BC et al (2013) MR imaging-guided focused ultrasound for treatment of bone metastasis. Radiographics 33:1555–1568

    Article  Google Scholar 

  17. Phenix CP, Togtema M, Pichardo S, Zehbe I, Curiel L (2014) High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery. J Pharm Pharm Sci 17:136–153

    Article  Google Scholar 

  18. Mitsunobu M, Toyosaka A, Oriyama T, Okamoto E, Nakao N (1996) Intrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel. Clin Exp Metastasis 14:520–529

    Article  CAS  Google Scholar 

  19. Francica G, Meloni MF, Riccardi L et al (2018) Ablation treatment of primary and secondary liver tumors under contrast-enhanced ultrasound guidance in field practice of interventional ultrasound centers. A multicenter study. Eur J Radiol 105:96–101

    Article  Google Scholar 

  20. Chen S, Peng Z, Lin M et al (2018) Combined percutaneous radiofrequency ablation and ethanol injection versus hepatic resection for 2.1-5.0 cm solitary hepatocellular carcinoma: a retrospective comparative multicentre study. Eur Radiol 28:3651–3660

    Article  Google Scholar 

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Funding

This study has received funding by the National Natural Science Foundation of China (Grant No. 81601511).

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Author notes

  1. Wei Qiao and Yanlan Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China

    Wei Qiao, Yanlan Yu, Ye Huang, Wenhong Gao & Zheng Liu

Authors
  1. Wei Qiao
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  2. Yanlan Yu
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  3. Ye Huang
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  4. Wenhong Gao
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  5. Zheng Liu
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Corresponding author

Correspondence to Zheng Liu.

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Guarantor

The scientific guarantor of this publication is Dr. Liu Zheng.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Approval from the institutional animal care committee was obtained.

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Institutional Review Board approval was obtained.

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Supplementary Figure

Photographs of haematoxylin and eosin staining. The ablation zone was seen around the central vein area (black arrow), surrounded by normal liver tissue in the EA-treated liver (A). A visible boundary was present between the necrotic liver and live liver tissues (black arrows) with infiltration of the inflammatory cells into the periphery of the necrotic area 48 h after treatment (B). Necrotic tumour cells showed marked karyolysis and karyopyknosis with wider intercellular interspaces than live tumour cells (C). A visible boundary was present between the live tumour cells and normal liver tissues (black arrows) (D). (DOCX 900 kb)

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Qiao, W., Yu, Y., Huang, Y. et al. Impact of focused ultrasound on the ethanol ablation of VX2 liver tumours in rabbits. Eur Radiol 30, 5862–5870 (2020). https://doi.org/10.1007/s00330-020-06941-3

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  • DOI: https://doi.org/10.1007/s00330-020-06941-3

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