Background: Pancreatic cancers can involve large blood vessels early, making complete resection technically challenging or impossible. A minimally invasive treatment that clears vessels from encasing tumours could potentially enable curative surgery. We hypothesise that Endovascular Photo-activated Ablation (EPA) of perivascular tumour tissue can create a necrotic zone free of viable tumour between cancer and blood vessels, through which the tumour could be resected. Methods: A dose escalation study was conducted in the normal porcine model (n= 7). Under general anaesthesia, the animals were given a photo-activated drug and photo-activation was provided by a prototype balloon catheter, positioned in a major blood vessel within the pancreas, under angiographic guidance. Contrast-enhanced CT scans were undertaken prior to and 1, 2, or 7 days following ablation. The animals were euthanised and the exposed tissue excised en bloc for histological examination. Results: Five animals were euthanised after 2 days. On post-mortem, the histology confirmed necrotic pancreas in the perivascular zone, which increased from zero to 15 mm around the treated vessel, for increasing drug doses. Treated arteries showed necrotising arteritis, without evidence of perforation or obstruction during the observation period, although one animal was euthanised at 1 day, due to technical endovascular device issues and obstruction. The lowest-dose animal euthanised at 7 days showed no lesions on pathology. Conclusions: These proof-of-concept results demonstrate that EPA can produce pancreatic perivascular necrosis in a large animal model. In a pancreatic cancer abutting a major blood vessel, this procedure may be able to create a zone free of viable tumour, potentially rendering these cancers operable, while preserving vessel integrity. These findings support further research activities towards clinical translation.
背景:胰腺癌早期即可侵犯大血管,导致完全切除在技术上具有挑战性或无法实现。一种能够清除血管周围肿瘤的微创治疗方法,可能使根治性手术成为可能。我们假设,通过血管内光激活消融(EPA)处理血管周围肿瘤组织,可在肿瘤与血管之间形成无活性肿瘤的坏死区域,从而为肿瘤切除创造条件。 方法:在正常猪模型(n=7)中进行剂量递增研究。在全麻下,动物接受光激活药物,并通过原型球囊导管在血管造影引导下,于胰腺内主要血管中进行光激活。消融前及消融后1、2或7天进行增强CT扫描。动物被安乐死后,整块切除暴露组织进行组织学检查。 结果:5只动物在2天后被安乐死。尸检组织学证实,随着药物剂量增加,血管周围区域出现胰腺坏死,坏死范围从零扩展至治疗血管周围15毫米。治疗动脉显示坏死性动脉炎,观察期间未见穿孔或阻塞证据,但有一只动物因血管内器械技术问题及阻塞在1天后被安乐死。最低剂量组动物在7天后安乐死,病理检查未见病变。 结论:这些概念验证结果表明,EPA能够在大动物模型中产生胰腺血管周围坏死。对于紧邻大血管的胰腺癌,该操作可能创建无活性肿瘤区域,有望使这些癌症具备手术条件,同时保持血管完整性。这些发现支持进一步开展临床转化研究。