Scheffer H J, Nielsen K, van Tilborg A A J M, Vieveen J M, Bouwman R A, Kazemier G, Niessen H W M, Meijer S, van Kuijk C, van den Tol M P, Meijerink M R
Department of Radiology and Nuclear Medicine, VU University Medical Centre, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands,
Eur Radiol. 2014 Oct;24(10):2467-75. doi: 10.1007/s00330-014-3259-x. Epub 2014 Jun 18.
Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility.
Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3).
Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens.
This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation.
• Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. • The ablation zone shows a sharp demarcation between avital and vital tissue. • Apoptosis is involved in cell death of colorectal liver metastases after IRE. • Effects of IRE can be monitored real-time using intraoperative ultrasound. • Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols.
不可逆电穿孔(IRE)是一种依赖高压电脉冲的新型消融技术。本临床研究评估IRE治疗结直肠癌肝转移(CRLM)的病理反应以及临床安全性和可行性。
纳入10例可切除CRLM患者。在剖腹手术期间,对转移灶进行IRE治疗,并在60分钟后切除。根据不良事件、实验室检查值、技术成功率和术中超声检查结果评估安全性和可行性。使用氯化三苯基四氮唑(TTC)活力染色和(免疫)组织化学染色(苏木精-伊红染色、补体3d和半胱天冬酶-3)评估组织反应。
平均直径为2.4厘米的10个病灶成功进行电穿孔,平均84分钟后(范围51 - 153分钟)切除。IRE期间发生1例轻微短暂性心律失常。超声显示肿瘤周围有界限清晰的低回声消融区。TTC显示所有病灶均无活力,8/10个病灶完全覆盖肿瘤。尽管免疫组织化学证明肿瘤内异质性且难以解释,但证实所有标本切缘无肿瘤处存在不可逆细胞损伤。
这项切除前消融研究证明IRE可导致人体CRLM无活力。有必要进一步表征组织和肿瘤特异性电特性,以改进消融方案,实现最大程度的组织消融。
• 不可逆电穿孔在1小时内可诱导结直肠癌肝转移细胞死亡。• 消融区在无活力组织和有活力组织之间界限清晰。• 凋亡参与IRE后结直肠癌肝转移细胞死亡。• 可使用术中超声实时监测IRE效果。• 肿瘤组织的局部电异质性可能需要肿瘤特异性消融方案。