Novel method to prevent severe postoperative pancreatic fistula caused by lipolysis

IF 3.2 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Journal of Hepato‐Biliary‐Pancreatic Sciences Pub Date : 2025-03-05 DOI:10.1002/jhbp.12128

Naoto Nakamura, Kazuyuki Nagai, Akihiro Kaneda, Akitada Yogo, Yosuke Kasai, Takayuki Anazawa, Yuichiro Uchida, Toshihiko Masui, Yasuhiko Tabata, Etsuro Hatano

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引用次数: 0

Abstract

Background

Although several prophylactic strategies have been developed for postoperative pancreatic fistula (POPF), research on its severe form is few. Recently, it has been reported that severe POPF can be caused by intraabdominal lipolysis. This study aimed to establish a rat model of severe POPF by combining pancreatic juice leakage and lipolysis and to develop a prophylactic strategy for POPF.

Methods

Sprague–Dawley rats were subjected to pancreatic transection to induce pancreatic juice leakage (PT group). Autologous fat tissue was thermally treated to prepare a fat solution, which was intraperitoneally administered to the rats in the PT group (PT + F group). A water-solubilized lipase inhibitor (cetilistat) was administered intraperitoneally to the rats in the PT + F group. A polyethylene glycol-based hydrogel (PEG-HG) formulation of water-solubilized cetilistat was equally administered. Ascitic and serum biochemical tests, including free fatty acids (FFA) levels, macroscopic or microscopic examinations, and survival analyses, were performed.

Results

In the PT + F group, significantly elevated ascitic and serum FFA levels and serum inflammatory cytokine levels were observed 24 h postoperatively (p < .001), and the survival rate was significantly exacerbated (p < .0001). Intraperitoneal administration of water-solubilized cetilistat resulted in reduced inflammation and improved outcomes. Although PEG hydrogel itself did not improve blood parameters or survival outcomes, the incorporation of water-solubilized cetilistat into the PEG-HG enabled similar improvement.

Conclusion

Intraperitoneal administration of water-solubilized cetilistat prevented severe inflammation and multiple failures associated with severe POPF. The incorporation of water-solubilized cetilistat into the PEG-HG is a promising delivery system for clinical application.

Abstract Image

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预防脂肪溶解术后严重胰瘘的新方法。

背景：虽然针对术后胰瘘（POPF）已经制定了几种预防策略，但对其严重形式的研究很少。最近，有报道称严重的POPF可由腹腔内脂肪溶解引起。本研究旨在建立胰漏和脂解联合大鼠重度胰瘘模型，探讨胰瘘的预防策略。方法：取Sprague-Dawley大鼠胰横断诱导胰漏（PT组）。PT组（PT + F组）采用自体脂肪组织热处理制备脂肪溶液，腹腔注射。PT + F组大鼠腹腔注射水溶性脂肪酶抑制剂西替司他。同样给予水溶性西司他的聚乙二醇基水凝胶（PEG-HG）制剂。进行腹水和血清生化试验，包括游离脂肪酸（FFA）水平、宏观或显微镜检查和生存分析。结果：PT + F组术后24 h腹水和血清FFA水平及血清炎性细胞因子水平均显著升高(p结论：腹腔给予水溶性西司他可预防严重POPF相关的严重炎症和多重衰竭。水溶性西司他掺入PEG-HG是一种具有临床应用前景的给药系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Hepato‐Biliary‐Pancreatic Sciences GASTROENTEROLOGY & HEPATOLOGY-SURGERY

自引率

10.00%

发文量

178

审稿时长

6-12 weeks

期刊介绍： The Journal of Hepato-Biliary-Pancreatic Sciences (JHBPS) is the leading peer-reviewed journal in the field of hepato-biliary-pancreatic sciences. JHBPS publishes articles dealing with clinical research as well as translational research on all aspects of this field. Coverage includes Original Article, Review Article, Images of Interest, Rapid Communication and an announcement section. Letters to the Editor and comments on the journal’s policies or content are also included. JHBPS welcomes submissions from surgeons, physicians, endoscopists, radiologists, oncologists, and pathologists.