Clinical Research and Medical Innovation Center, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan.
Division of Endoscopy, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-Ku, Sapporo, 060-8648, Japan.
Surg Endosc. 2023 Oct;37(10):8029-8034. doi: 10.1007/s00464-023-10243-2. Epub 2023 Jul 19.
Anastomotic leakage (AL) after gastrointestinal surgery remains a challenging complication that requires surgical or non-surgical treatment. Although various therapeutic endoscopic techniques are available, no definitive interventions exist. We developed a therapeutic endoscopic submucosal injection method using novel gel-forming mixed solutions to close AL and evaluated the elasticity of the developed hydrogel. The safety and efficacy of the injection method were explored in porcine AL models.
We developed a novel gel-forming solution, and the formed gel lasted approximately one week within the gastrointestinal wall. An indentation test evaluated the elasticity of the novel hydrogel. After the confirmation of AL on porcine anterior gastric walls, sodium alginate was endoscopically injected into the submucosal layer around the leakage site circularly, followed by a calcium lactate/chitosan-based solution. After that, the outcomes data were collected, and histopathological effectiveness was evaluated.
The increased sodium alginate elasticity with the addition of calcium lactate/chitosan-based solution facilitated long-lasting gel formation. Four pigs with AL underwent this intervention consecutively. Each endoscopic injection was completed in less than 5 min. No significant complications were observed for 3 weeks after the intervention. All AL sites were macroscopically healed. Histopathologic findings at 3 weeks showed that the wall defect was filled with collagen fibers that had grown around the site of the muscle layer tear. No tissue necrosis was observed.
This preclinical study demonstrated that the therapeutic injection method for gastroenterological AL using gel-forming solutions could be an alternative endoscopic treatment, especially in patients with severe conditions or comorbidities. The optimal target of this treatment is small size and early AL without poor blood flow or intense hypertrophic scar lesions.
胃肠道手术后吻合口漏（AL）仍然是一种具有挑战性的并发症，需要手术或非手术治疗。尽管有各种治疗性内镜技术，但尚无明确的干预措施。我们开发了一种使用新型凝胶形成混合溶液的治疗性内镜黏膜下注射方法来闭合 AL，并评估了所开发水凝胶的弹性。在猪 AL 模型中探索了注射方法的安全性和有效性。
我们开发了一种新型凝胶形成溶液，形成的凝胶在胃肠道壁内大约持续一周。压痕试验评估了新型水凝胶的弹性。在前胃猪壁确认 AL 后，将海藻酸钠内镜下环形注射到渗漏部位的黏膜下层，然后注射乳酸钙/壳聚糖溶液。然后收集结果数据并评估组织病理学效果。
添加乳酸钙/壳聚糖溶液后，海藻酸钠的弹性增加，有利于形成持久的凝胶。连续对 4 头患有 AL 的猪进行了这种干预。每次内镜注射都在 5 分钟以内完成。干预后 3 周内未观察到明显的并发症。所有 AL 部位均在宏观上愈合。3 周时的组织病理学发现表明，壁缺损被围绕肌肉层撕裂部位生长的胶原纤维填充。未观察到组织坏死。
这项临床前研究表明，使用凝胶形成溶液治疗胃肠道 AL 的治疗性注射方法可能是一种内镜治疗的替代方法，特别是在病情严重或合并症患者中。这种治疗的最佳目标是小尺寸和早期 AL，没有血流不良或强烈的肥厚性瘢痕病变。
