Abstract

Background and Aims: Irreversible electroporation (IRE) is a promising, non-thermal ablation therapy for hepatocellular carcinoma, which, unlike radiofrequency thermal ablation (RFA), induces apoptosis through irreversible formation of nanoscale pores in the cell membrane with delivery of high-voltage electric current and is considered to improve safety in the vicinity of heat-sensitive blood vessel and bile duct. The aim of the present study is to clarify the acute pathological effect of IRE on the liver and also to compare with effect of RFA. Methods: Three pigs underwent ultrasound-guided IRE and RFA of normal liver under general anesthesia and at laparotomy. A total of 9 IRE ablated areas and 3 RFA ablated areas were created. We examined histopathologic findings of ablated areas at 4 hours after therapy with immunohistochemical methods. The pathologic findings according to IRE ablation conditions were compared with findings of RFA. Results: In IRE zones, various degree of congestion and hemorrhage, apoptotic change of hepatocytes, defluxion of portal endothelial cells and cholangitis were observed in hepatic lobules. With the increase in the total pulse number of IRE delivered, these pathological findings became remarkable. NADPH-diaphorase enzyme histochemistry performed in IRE zones demonstrated the stainability is very weak in the hepatic lobule, which reflecting defluxion of hepatocytes and reduced activity of viable hepatocytes in acute phase, while the stainability is lost in the central portion of RFA. Silver impregnation stain and collagen type 4 immunohistochemistry showed that reticular fibers and collagen fibers around the sinusoid remain well-preserved in IRE zones, on the other hand, those in RFA zones are very poorly stained. The vessels in IRE zones demonstrated a relatively intact configuration of positive smooth muscle cells for Caldesmon staining and endothelial cells for Factor 8 staining, with the minimal endothelial damage, while the vessels in RFA zones demonstrated a negative or weakened reaction. Bile duct epithelial cells showed a positive reaction for cytokeratin 7 staining in IRE zones with desquamated cells, while an entirely negative reaction in RFA zones, revealing protein denaturation. Conclusions: Unlike RFA, IRE induces apoptosis of hepatocytes, endothelium of the blood vessels and mucosal membrane of the bile ducts, whereas preservation of sinusoidal framework and vascular structure may have the potential for liver regeneration.

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