射频消融诱导肝癌小鼠模型中的肿瘤细胞播散。

Radiofrequency ablation induces tumor cell dissemination in a mouse model of hepatocellular carcinoma.

机构信息

Department of Medical Ultrasonics, The First Affiliated Hospital of Sun Yat-Sen University, Institute of Diagnostic and Interventional Ultrasound, Guangzhou, 510080, China.

Biomedical Engineering Research Center, Kunming Medical University, Kunming, China.

出版信息

Eur Radiol Exp. 2023 Nov 29;7(1):74. doi: 10.1186/s41747-023-00382-5.

DOI:10.1186/s41747-023-00382-5

PMID:38019353

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10686970/

Abstract

BACKGROUND

We tested the hypothesis that radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) promotes tumor cell release and explored a method for reducing these effects.

METHODS

A green fluorescent protein-transfected orthotopic HCC model was established in 99 nude mice. In vivo flow cytometry was used to monitor circulating tumor cell (CTC) dynamics. Pulmonary fluorescence imaging and pathology were performed to investigate lung metastases. First, the kinetics of CTCs during the periablation period and the survival rate of CTCs released during RFA were investigated. Next, mice were allocated to controls, sham ablation, or RFA with/without hepatic vessel blocking (ligation of the portal triads) for evaluating the postablation CTC level, lung metastases, and survival over time. Moreover, the kinetics of CTCs, lung metastases, and mice survival were evaluated for RFA with/without ethanol injection. Pathological changes in tumors and surrounding parenchyma after ethanol injection were noted. Statistical analysis included t-test, ANOVA, and Kaplan-Meier survival curves.

RESULTS

CTC counts were 12.3-fold increased during RFA, and 73.7% of RFA-induced CTCs were viable. Pre-RFA hepatic vessel blocking prevented the increase of peripheral CTCs, reduced the number of lung metastases, and prolonged survival (all p ≤ 0.05). Similarly, pre-RFA ethanol injection remarkably decreased CTC release during RFA and further decreased lung metastases with extended survival (all p ≤ 0.05). Histopathology revealed thrombus formation in blood vessels after ethanol injection, which may clog tumor cell dissemination during RFA.

CONCLUSION

RFA induces viable tumor cell dissemination, and pre-RFA ethanol injection may provide a prophylactic strategy to reduce this underestimated effect.

RELEVANCE STATEMENT

RFA for HCC promotes viable tumor cell release during ablation, while ethanol injection can prevent RFA induced tumor cell release.

KEY POINTS

• RFA induced the release of viable tumor cells during the ablation procedure in an animal model. • Hepatic vessel blocking can suppress tumor cells dissemination during RFA. • Ethanol injection can prevent RFA-induced tumor cell release, presumably because of the formation of thrombosis.

摘要

背景

我们检验了这样一个假设，即射频消融（RFA）治疗肝细胞癌（HCC）会促进肿瘤细胞释放，并探索了一种减少这种影响的方法。

方法

在 99 只裸鼠中建立了绿色荧光蛋白转染的原位 HCC 模型。使用体内流式细胞术监测循环肿瘤细胞（CTC）的动态变化。进行肺部荧光成像和病理学检查以研究肺转移。首先，研究了消融期间 CTC 的动力学以及 RFA 过程中释放的 CTC 的存活率。然后，将小鼠分为对照组、假消融组或 RFA 组（联合或不联合肝血管阻断，即门静脉三联阻断），以评估消融后 CTC 水平、肺转移和随时间的生存情况。此外，还评估了 RFA 联合或不联合乙醇注射时 CTC 的动力学、肺转移和小鼠的生存情况。注意乙醇注射后肿瘤和周围实质的病理变化。统计分析包括 t 检验、方差分析和 Kaplan-Meier 生存曲线。

结果

RFA 过程中 CTC 计数增加了 12.3 倍，73.7%的 RFA 诱导的 CTC 是有活力的。RFA 前肝血管阻断可防止外周 CTC 增加，减少肺转移数量并延长生存时间（均 p≤0.05）。同样，RFA 前乙醇注射可显著减少 RFA 过程中 CTC 的释放，并进一步减少肺转移，延长生存时间（均 p≤0.05）。组织病理学显示乙醇注射后血管内形成血栓，这可能在 RFA 过程中阻止肿瘤细胞的扩散。