国产新型内镜夹治疗消化道穿孔的临床前动物实验研究

A preclinical animal study on a novel domestic endoscopic clip for digestive tract perforation

摘要:

目的 评估国产新型内镜夹治疗消化道穿孔的可行性、安全性和有效性，探讨其后续临床研究及推广价值。方法 8头健康白猪纳入临床前动物实验，采用随机数字表法随机分配到国产新型内镜夹闭合组（实验组）或耙状金属夹闭合系统（over?the?scope?clip system，OTSC）闭合组（对照组）。每头实验猪的胃部及直肠部各构建1个穿孔，直径2 cm左右，每构建完1个穿孔即行内镜夹全层闭合，按随机分组结果使用相应的内镜夹，术中观察内镜夹的操作性能、不良事件发生情况及即刻闭合是否成功。术后第3、7、14、21、35天行内镜检查，评估内镜夹的夹持及创面愈合情况。术后第35天观察期结束时，处死实验猪，评估创面愈合情况，并对创面部位进行组织病理学检查。结果 实验组和对照组各4头实验猪。2组胃部及直肠部人造穿孔均顺利完成即刻闭合，均未发生误激发、器械损坏、输送系统操作失灵等术中不良事件。胃部内镜夹操作性能评分：对照组4头均达3分，实验组有3头达3分，另一头为2分；直肠部内镜夹操作性能评分：2组各有3头达3分，实验组另一头为1分，对照组另一头为2分。2组观察期内实验猪均存活，均未发生术后并发症。有1枚内镜夹（对照组，直肠创面）在观察期内自然脱落，其他内镜夹均在位。尸检大体标本检查结果显示，8头实验猪的胃部和7头实验猪的直肠部手术创面闭合处均已愈合，创面愈合程度评分均达3分，另一头（对照组）的直肠黏膜切口愈合欠佳，伤口红肿未消退，创面愈合程度评分为2分。尸检组织病理学结果显示，2组炎症反应、细胞坏死及血管增殖情况相似，均无溃疡形成。结论 国产新型内镜夹用于消化道穿孔治疗，在可行性、安全性和有效性方面与OTSC具有可比性，具有良好的临床应用前景，值得进一步临床研究及推广。

Abstract:

Objective To evaluate the feasibility, safety and efficacy of a domestic novel endoscopic clip for the treatment of gastrointestinal perforation in an animal model, and discuss its potential clinical adoption. Methods Eight experimental pigs were randomly assigned to either an experimental group receiving the domestic novel endoscopic clip or a control group receiving an over-the-scope clip system (OTSC) using the random number table. Each animal underwent the creation of 2 cm perforations in the stomach and rectum, which were immediately sealed with clips. The performance, safety, and immediate closure rate of the clips during surgery were evaluated. Endoscopic examinations were conducted on days 3, 7, 14, 21, and 35 post-surgery to assess clip retention and wound healing. At the end of the observation period, animals were euthanized to evaluate wound healing, and histological examinations of the wound sites were conducted. Results Both groups, consisting of 4 pigs each, successfully created and closed artificial perforations in both the stomach and rectum without intraoperative adverse events in either group such as accidental activation, device failure, or malfunctions in the delivery system. Endoscopic clip performance in the stomach were uniformly rated as 3 in all 4 pigs in the control group, while in the experimental group, 3 pigs were scored as 3 and 1 as 2. For rectal clip performance, 3 pigs were scored as 3 in both groups. One pig were scored as 1 in the experimental group, and the remaining pig in the control group were 2. All pigs survived the observation period without any postoperative complications. One clip (in the control group, rectal site) naturally dislodged during the observation period, while the other clips remained in place. Gross pathological examination revealed that the gastric surgical sites in all 8 pigs and the rectal sites in 7 pigs had healed, with wound healing scores of 3. However, 1 pig (control group) exhibited poor healing of the rectal mucosal incision, with persistent redness and swelling, and a wound healing score of 2. Histopathological examination showed similar levels of inflammation, cell necrosis, and vascular proliferation between the two groups, without ulcer formation observed. Conclusion The domestically produced novel endoscopic clip exhibits simplicity in operation and demonstrates comparable technical feasibility, safety, and efficacy to OTSC. Its promising clinical application warrants further investigation and promotion through additional clinical research.