Zardi Enrico M, Borzomati Domenico, Cacciapaglia Fabio, Picardi Antonio, Valeri Sergio, Bianchi Antonella, Galeotti Tommaso, Coppolino Giusy, Coppola Roberto, Afeltra Antonella
Department of Clinical Medicine Campus Bio-Medico University, Rome, Italy.
BMC Gastroenterol. 2007 Dec 13;7:45. doi: 10.1186/1471-230X-7-45.
To compare tumor necrosis in hepatoma induced in rats by a single percutaneous injection of ethanol (PEI) or acetic acid (PAI).
BW7756 hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14 days, the 36 surviving rats were treated, in a single session, by ultrasound-guided injection of 300 microl of 95% ethanol (n = 17) or 100 microl of 50% acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted tumoral livers were examined. The same PAI procedure was repeated on 13 additional rats to exclude a suspected occurrence of technical failures during the experiment, due to a surprisingly high rate of deaths within 30 minutes after PAI.
Four rats died within four days after tumor implantation; after PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats, after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic examinations showed that the hepatoma's nodules treated with PEI had 45.3 +/- 19.4% tumor necrosis compared to 49 +/- 23.3% (P = NS) for those treated with PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively (P = NS). Autopsy was performed in the 5 additional rats that died within 30 minutes after PAI.
Our results show that there is no significant difference in the percentage of tumor necrosis between two local ablation methods in spite of the different dosages used. However, mortality in the PAI-treated group was greater than in PEI-treated group, presumably due to greater acetic acid systemic diffusion and its metabolic side effects. In human subjects, HCC occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than the tumor structure, with consequent reduction of drug diffusion. This could be the reason why some human studies have concluded similar or even better safety and efficacy with PAI compared to PEI.
比较单次经皮注射乙醇(PEI)或乙酸(PAI)诱导大鼠肝癌后的肿瘤坏死情况。
将体积为1mm³的BW7756肝癌植入40只雄性健康大鼠的肝脏。14天后,对36只存活大鼠进行单次治疗,通过超声引导注射300微升95%乙醇(n = 17)或100微升50%乙酸(n = 19)。治疗14天后将它们处死,并检查切除的肿瘤肝脏。对另外13只大鼠重复PAI操作,以排除实验过程中因PAI后30分钟内意外高死亡率而怀疑出现的技术故障。
4只大鼠在肿瘤植入后4天内死亡;PEI治疗后,1/17(6%)死亡,而PAI治疗后9/19(47%)死亡。经皮消融14天后,其余26只大鼠被处死。大体和显微镜检查显示,PEI治疗的肝癌结节肿瘤坏死率为45.3±19.4%,而PAI治疗的为49±23.3%(P = 无显著性差异)。任何动物均未发现完全肿瘤坏死。PEI或PAI治疗的大鼠中分别有4/16(25%)和2/10(20%)出现腹膜侵犯(P = 无显著性差异)。对PAI后30分钟内死亡的另外5只大鼠进行了尸检。
我们的结果表明,尽管使用的剂量不同,但两种局部消融方法之间的肿瘤坏死百分比无显著差异。然而,PAI治疗组的死亡率高于PEI治疗组,可能是由于乙酸全身扩散及其代谢副作用更大。在人类受试者中,肝癌发生在肝硬化背景下,其中非肿瘤组织比肿瘤结构更硬,从而导致药物扩散减少。这可能是一些人体研究得出PAI与PEI相比具有相似甚至更好的安全性和疗效的原因。