Intraperitoneal administration of a thermogel combined with an anticancer agent for the prevention of peritoneal carcinomatosis in a pig model.

IF 3.5 2区 医学 Q2 ONCOLOGY
Ejso Pub Date : 2024-10-28 DOI:10.1016/j.ejso.2024.108787
Agathe Thouvenin, Nawar Al Chirazi, Johanne Seguin, Cynthia Crocheray, Joël Poupon, Rachid Kaci, Nathalie Mignet, Vincent Boudy, Marc Pocard
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引用次数: 0

Abstract

Background: Surgeons may discover perioperative clinical situations associated with an increased risk of peritoneal carcinomatosis recurrence after primary resection. We developed a thermogel that can be used as a drug carrier to deliver an anticancer agent in the peritoneal cavity as a rescue solution. The spatial distribution of the thermogel and pharmacokinetics of chemotherapy have been studied in pigs. The safety of the thermogel was assessed based on the healing of bowel sutures.

Methods: Nine pigs received gel with oxaliplatin at 130 mg/200 mL (TG-Ox group), and 4 pigs received the gel alone (TG group). Digestive tract and bladder wounds were made and sutured. Pigs were sacrificed at different times after surgery to monitor the distribution of the thermogel and to detect the occurrence of bowel fistulas. Oxaliplatin plasma and tissue concentrations were determined via mass spectrometry.

Results: After 3 h, 100 % of the regions of interest were covered by the gel, 78 % were covered after 2 days, and 38 % were covered after 4 days. The thermogel delayed the release of oxaliplatin into the systemic circulation and significantly prolonged tissue impregnation. Anastomotic fistulas were observed in the TG-Ox group (10 %) versus 0 % in the TG group (p = 0.31).

Conclusions: A homogeneous distribution of the thermogel throughout the peritoneal cavity was observed, and the thermogel fulfilled its functions as a drug carrier, including ensuring safety and delaying chemotherapy delivery. Treatment-induced toxicity due to oxaliplatin was identified. The concept of a rescue solution being available in operating rooms was demonstrated.

在猪模型中腹膜内注射热凝胶和抗癌剂以预防腹膜癌。
背景:外科医生可能会发现围手术期的临床情况与原发性切除术后腹膜癌复发风险增加有关。我们开发了一种热凝胶,可用作药物载体,在腹腔内输送抗癌剂作为抢救溶液。我们在猪身上研究了热凝胶的空间分布和化疗的药代动力学。根据肠缝线的愈合情况评估了热凝胶的安全性:方法:9 头猪接受了含有 130 毫克/200 毫升奥沙利铂的凝胶(TG-Ox 组),4 头猪只接受了凝胶(TG 组)。制作并缝合消化道和膀胱伤口。猪在手术后的不同时间被处死,以监测热凝胶的分布情况并检测肠瘘的发生。通过质谱法测定奥沙利铂的血浆和组织浓度:3小时后,凝胶覆盖了100%的相关区域,2天后覆盖了78%,4天后覆盖了38%。热凝胶延缓了奥沙利铂向全身循环的释放,并显著延长了组织浸渍的时间。TG-Ox组出现吻合口瘘的比例为10%,而TG组为0%(P = 0.31):结论:观察到热凝胶在整个腹腔内均匀分布,热凝胶实现了其作为药物载体的功能,包括确保安全和延迟化疗给药。发现了奥沙利铂引起的治疗毒性。在手术室提供抢救解决方案的概念得到了验证。
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来源期刊
Ejso
Ejso 医学-外科
CiteScore
6.40
自引率
2.60%
发文量
1148
审稿时长
41 days
期刊介绍: JSO - European Journal of Surgical Oncology ("the Journal of Cancer Surgery") is the Official Journal of the European Society of Surgical Oncology and BASO ~ the Association for Cancer Surgery. The EJSO aims to advance surgical oncology research and practice through the publication of original research articles, review articles, editorials, debates and correspondence.
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