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丝裂霉素-C缺氧停流灌注治疗多灶性肝转移。血管动脉支架预防肝动脉壁医源性损伤的效用。

Hypoxic stop-flow perfusion with mitomycin-C in the treatment of multifocal liver metastases. Usefulness of a vascular arterial stent to prevent iatrogenic lesions of the hepatic arterial wall.

作者信息

Gadaleta C D, Catino A, Ranieri G, Armenise F, Console G, Mattioli V

机构信息

Interventional Radiology Operative Unit, Oncology Institute, Bari, Italy.

出版信息

J Exp Clin Cancer Res. 2003 Dec;22(4 Suppl):203-6.

Abstract

13 patients affected by multifocal and/or large liver metastases from various solid tumors have been treated with stop-flow liver perfusion, to evaluate the safety and feasibility of hypoxic loco-regional infusion with Mitomycin C. The treatment was based on the hypoxic effect due to stop-flow, potentiating the cytotoxic activity of Mitomycin C, combined with the ischemic damage caused by the embolization of the vascular supply to the tumor. The schedule consisted in blocking arterial flow by an angiographic occlusion balloon catheter inflated in the hepatic artery, with previous placement of a vascular stent in order to prevent iatrogenic arterial lesions, and followed by the intraarterial administration of Mitomycin C; finally, arterial hepatic embolization was performed by a gelatine sponge. The study is ongoing with a median follow up of 8 months (range 2-12). Partial response was observed in 1/13 patients (8%), stable disease in 8/13 patients (61%), while progressive disease occurred in 4/13 patients (31%). Nine patients are still alive, and four patients died for hepatic progressive disease, three of them heavily pre-treated with multiple lines of chemotherapy for advanced disease. Toxicity was mild; main side effects were anaemia and thrombocytopenia(Grade 3 both in 1/15 treatments), while fever, nausea and vomiting and upper abdominal pain were short-lasting and easily manageable. No iatrogenic lesion of the hepatic arterial wall occurred. These preliminary data, although the small number of patients and the short follow up, show that the procedure is safe and feasible, with a interesting percentage of clinical responses. In addition, the placement of an arterial stent have demonstrated to protect vascular wall ensuring a regular blood flow, so allowing to perform repeated treatments in responsive patients. The good tolerability of this therapeutic modality suggests further investigation in order to determine its efficacy even in combination with systemic chemotherapy and other locoregional treatments such as termoablative procedures and/or intraarterial antiblastic perfusions in patients affected by metastatic liver disease.

摘要

13例患有源自各种实体瘤的多灶性和/或大型肝转移瘤的患者接受了停流肝灌注治疗,以评估丝裂霉素C低氧局部灌注的安全性和可行性。该治疗基于停流导致的低氧效应,增强丝裂霉素C的细胞毒性活性,同时结合肿瘤血管供应栓塞引起的缺血性损伤。治疗方案包括通过在肝动脉中膨胀的血管造影闭塞球囊导管阻断动脉血流,在此之前放置血管支架以防止医源性动脉病变,随后进行丝裂霉素C的动脉内给药;最后,用明胶海绵进行肝动脉栓塞。该研究正在进行中,中位随访时间为8个月(范围2 - 12个月)。1/13例患者(8%)观察到部分缓解,8/13例患者(61%)病情稳定,而4/13例患者(31%)出现疾病进展。9例患者仍然存活,4例患者死于肝脏疾病进展,其中3例因晚期疾病接受了多线化疗的重度预处理。毒性轻微;主要副作用是贫血和血小板减少(1/15次治疗中均为3级),而发热、恶心、呕吐和上腹部疼痛持续时间短且易于控制。未发生肝动脉壁的医源性病变。这些初步数据,尽管患者数量少且随访时间短,但表明该手术是安全可行的,具有可观的临床缓解率。此外,动脉支架的放置已证明可保护血管壁,确保正常血流,从而允许对有反应的患者进行重复治疗。这种治疗方式的良好耐受性表明需要进一步研究,以确定其与全身化疗以及其他局部治疗(如热消融手术和/或动脉内抗瘤灌注)联合应用于转移性肝病患者时的疗效。

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