Abstract
Inoperable liver tumors are often treated by thermal ablation that destroys the tumor in situ and spares the adjacent hepatic tissue. Thermal–physical treatment has many advantages, but treatment by freezing or heating alone has some limitations. By taking the advantages and disadvantages of cryosurgery and thermotherapy into consideration, a new thermal technique that combines cryosurgery and radio frequency ablation has been proposed, thereby overcoming the disadvantages of each treatment strategy and improving therapeutic outcomes. This new approach remains to be systematically studied in the liver; therefore, this study was performed to estimate survival after alternated cooling and heating ablation therapy in a VX2 rabbit liver tumor model. Sixteen days after VX2 carcinoma implantation into the rabbit liver, tumors were treated with alternated cooling and heating ablation therapy. Rabbits were monitored for 6 months after treatment and assessed with ultrasound (US) and computed tomography at 1, 7, 14, and 30 days posttreatment. Untreated tumor-bearing animals served as the control group. Our results show that alternate freezing and heating ablation therapy resulted in a good recovery of VX2 rabbits. Compared with the control group, treated rabbits lived significantly longer (P < 0.05), with 70 % of treated animals surviving to 196 days posttreatment without metastasis or recurrence, while none of the controls did so. There was no local recurrence in the treatment group. All rabbits in the control group developed metastasis, while metastasis was only observed in 30 % of treated rabbits. These results suggest that alternate cooling and heating ablation therapy can prolong the survival time of rabbits with VX2 liver tumors and is an effective method for tumor therapy. Furthermore, we also showed in this model that contrast enhanced US is a valid follow-up approach to assess treatment effectiveness.






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References
He J, Gu D, Wu X et al (2005) Major causes of death among men and women in China. N Engl J Med 353:1124–1134
Llovet JM, Di Bisceglie AM, Bruix J et al (2008) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100:698–711
Webb H, Lubner MG, Hinshaw JL (2011) Thermal ablation. Semin Roentgenol 46:133–141
Seifert JK, Springer A, Baier P et al (2005) Liver resection or cryotherapy for colorectal liver metastases: a prospective case control study. Int J Colorectal Dis 20:507–520
Vanagas T, Gulbinas A, Pundzius J et al (2010) Radiofrequency ablation of liver tumors (II): clinical application and outcomes. Medicina (Kaunas) 46:81–88
Greenstein A, Koontz WW Jr (2002) Does local hyperthermia affect metastasis of a human prostate carcinoma grown in athymic nude mice? Int J Hyperthermia 18:285–291
Yang W, Ahmed M, Tasawwar B et al (2011) Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model. Int J Hyperthermia 27:527–538
Sun J, Luo X, Zhang A et al (2005) A new thermal system for tumor treatment. Conf Proc IEEE Eng Med Biol Soc 1:474–477
Sun J, Zhang A, Xu L (2008) Evaluation of alternate cooling and heating for tumor treatment. Int J Heat Mass Transf 51:5478–5485
Shen Y, Liu P, Zhang A et al (2005) Tumor microvasculature response to alternated cold and heat treatment. Conf Proc IEEE Eng Med Biol Soc 7:6797–6800
Gage AM, Montes M, Gage AA (1982) Destruction of hepatic and splenic tissue by freezing and heating. Cryobiology 19:172–179
Kuz’menko AP, Todor IN, Mosienko VS (1990) The effect of the combined use of cryosurgery and hyperthermia on an experimental tumor process. Eksp Onkol 12:60–61
Osinsky SP, Rikberg AB, Bubnovskaja LN et al (1993) Tumour pH drop after cryotreatment and enhancement of hyperthermia antitumour effect. Int J Hyperthermia 9:297–301
Hoffmann NE, Chao BH, Bischof JC (2000) Cryo, Hyper or Both? Investigating Combination Cyro/hyperthermia in the Dorsal Skin Flap Chamber. In: Proceedings of the ASME advances in heat and mass transfer in biotechnology 157–159
Liu J, Zhou Y, Yu T et al (2004) Minimally invasive probe system capable of performing both cryosurgery and hyperthermia treatment on target tumor in deep tissues. Minim Invasive Ther Allied Technol 13:47–57 PubMed: 16754125
Dong J, Liu P, Xu LX (2009) Immunologic response induced by synergistic effect of alternating cooling and heating of breast cancer. Int J Hyperthermia 25:25–33
Sun JQ, Xu CC, Wei GH et al (2009) Tumor treatment system with alternate cooling and heating-preliminary results in an animal model. IFMBE Proceedings 25:337–340
Zhou M, Zhang A, Lin B et al (2007) Study of heat shock response of human umbilical vein endothelial cells (HUVECs) using cDNA microarray. Int J Hyperthermia 23:225–258
Shen Y, Liu P, Zhang A et al (2008) Study on tumor microvasculature damage induced by alternate cooling and heating. Ann Biomed Eng 36:1409–1419
Xu LX, Zhang A, Liu P et al (2008) Energy-based diagnostic and treatment techniques. IEEE Eng Med Biol Mag 27:72–77
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Wei, C., Shen, E., Sun, D. et al. Assessment of alternated cooling and heating treatment by US combined CEUS in the VX2 rabbit liver tumor model. Chin. Sci. Bull. 59, 865–873 (2014). https://doi.org/10.1007/s11434-013-0098-0
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DOI: https://doi.org/10.1007/s11434-013-0098-0

