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正常肝组织和纤维肝组织对不可逆电穿孔的反应不同。

Normal and fibrotic liver parenchyma respond differently to irreversible electroporation.

机构信息

Department of Mechanical Engineering, University of California, Berkeley, CA 94720, USA.

Department of Surgery, University of California, San Francisco, CA 94143, USA.

出版信息

HPB (Oxford). 2019 Oct;21(10):1344-1353. doi: 10.1016/j.hpb.2019.01.019. Epub 2019 Mar 14.

Abstract

BACKGROUND

The safety and efficacy of irreversible electroporation (IRE) in treating hepatic, biliary, and pancreatic malignancies are active areas of clinical investigation. In addition, recent studies have shown that IRE may enable regenerative surgery and in vivo tissue engineering. To use IRE effectively in these clinical applications, it is important to understand how different tissue microenvironments impact the response to IRE. In this study, we characterize the electrical and histological properties of non-fibrotic and fibrotic liver parenchyma before and after IRE treatment.

METHODS

Electrical resistivity and histology of fibrotic liver from C57BL/6 mice fed a 0.1% 3,5-diethylcarbonyl-1,4-dihydrocollidine (DDC) diet were compared to those of non-fibrotic liver from matched control mice before and after IRE treatment.

RESULTS

At baseline, the electrical resistivity of fibrotic liver was lower than that of non-fibrotic liver. Post-IRE, resistivity of non-fibrotic liver declined and then recovered back to baseline with time, correlating with hepatocyte repopulation of the ablated parenchyma without deposition of fibrotic scar. In contrast, resistivity of fibrotic liver remained depressed after IRE treatment, correlating with persistent inflammation.

CONCLUSION

Non-fibrotic and fibrotic liver respond to IRE differently. The underlying tissue microenvironment is an important modifying factor to consider when designing IRE protocols for tissue ablation.

摘要

背景

不可逆电穿孔(IRE)在治疗肝、胆、胰腺恶性肿瘤方面的安全性和有效性是临床研究的活跃领域。此外,最近的研究表明,IRE 可能使再生手术和体内组织工程成为可能。为了在这些临床应用中有效地使用 IRE,了解不同的组织微环境如何影响对 IRE 的反应非常重要。在这项研究中,我们在 IRE 治疗前后对非纤维化和纤维化肝实质的电学和组织学特性进行了表征。

方法

比较了喂食 0.1% 3,5-二乙基羰基-1,4-二氢吡啶(DDC)饮食的 C57BL/6 小鼠的纤维化肝与匹配对照小鼠的非纤维化肝的电阻抗和组织学特性,以及 IRE 治疗前后的电阻抗和组织学特性。

结果

在基线时,纤维化肝的电阻抗低于非纤维化肝。IRE 后,非纤维化肝的电阻抗下降,随着时间的推移恢复到基线,与消融实质中肝细胞的再增殖而无纤维疤痕沉积相关。相比之下,IRE 治疗后纤维化肝的电阻抗仍然降低,与持续的炎症相关。

结论

非纤维化和纤维化肝对 IRE 的反应不同。在设计用于组织消融的 IRE 方案时,组织微环境是一个重要的考虑因素。

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