1 Hospital Universitario Infanta Elena, Madrid, 28342, Spain.
2 Hospital Clínico San Carlos, Madrid, 28040, Spain.
Exp Biol Med (Maywood). 2018 Jun;243(10):803-808. doi: 10.1177/1535370218777216.
The intestinal anastomotic failure is one of the most severe complications in gastrointestinal surgery. Despite the great surgical improvements during the last decade, anastomotic leak rates remain practically the same, with a dramatically high grade of morbidity for patients. Leakages are usually the final consequence of ischemia in the anastomosis, leading to tissue hypoxia. In response to hypoxia, the cell orchestrates a variety of coordinated responses in order to restore oxygen homeostasis. The molecular mechanism of hypoxia sensitivity involves oxygen sensing hydroxylases, prolyl-hydroxylases, orchestrating two main transcription factors related to induction of inflammation and angiogenesis, namely nuclear factor-κB and hypoxia-inducible factors. The immunohistochemical expression of two transcription factors hypoxia-inducible factors-1α and nuclear factor-κB p65 has already been described in several disorders, including wound healing, asthma and chronic obstructive lung disease, rheumatoid arthritis, cancer, inflammatory bowel disease, and acute colitis. In the surgical field, fibrin sealants have been widely used to prevent leaks in lung surgery and they might also be useful as a reinforcement of sutures in intestinal anastomosis. The commercial fibrin sealant patches are hemostatic and adhesive surgical agents mainly derived from human plasma. We herein report the results of a prospective randomized experimental study on pigs. We performed a high-risk leakage model of bowel anastomosis, causing a significant devascularization of 10-15 cm of the bowel wall before performing a conventional colo-ileal anastomosis. We randomized the animals to receive a covering of the anastomosis with a fibrin patch (case group) or not (control group). We report the changes in the immunohistochemical expression of the proteins involved in tissue response to hypoxia in the experimental model. Our results indicate that the fibrin patch delays the healing response, promoting a longer lasting inflammation in the surgical bed. Nevertheless, the fibrin patches effectiveness to reduce dehiscence shown in clinical practice suggests that this delay does not negatively affect patients' outcome. Impact statement The consequences of the anastomotic failure are dramatic for patients. Understanding how the ever-increasing use of fibrin sealant, that seems to have a beneficial effect on the anastomoses, interacts with the tissue and the healing process can help to justify its use and encourage research on how to improve this effect even more. We feel that the present work shows that the patch can improve healing by complex mechanisms other than the mere contention and physical support of the intestine. Furthermore, research is needed to confirm our preliminary findings.
肠吻合口失败是胃肠道手术中最严重的并发症之一。尽管在过去十年中外科技术有了很大的进步，但吻合口漏的发生率实际上仍然相同，患者的发病率极高。漏出通常是吻合口缺血的最终结果，导致组织缺氧。为了应对缺氧，细胞会协调各种协调反应，以恢复氧平衡。缺氧敏感性的分子机制涉及氧感应羟化酶、脯氨酰羟化酶，协调与炎症和血管生成诱导相关的两个主要转录因子，即核因子-κB 和缺氧诱导因子。两种转录因子缺氧诱导因子-1α 和核因子-κB p65 的免疫组化表达已在几种疾病中得到描述，包括伤口愈合、哮喘和慢性阻塞性肺疾病、类风湿关节炎、癌症、炎症性肠病和急性结肠炎。在外科领域，纤维蛋白密封剂已广泛用于预防肺手术中的漏液，它们也可能作为肠吻合的缝线加固剂有用。商业纤维蛋白密封贴片是止血和粘合的外科制剂，主要来源于人血浆。我们在此报告了一项关于猪的前瞻性随机实验研究的结果。我们进行了肠吻合的高风险漏液模型，在进行常规结肠-回肠吻合术之前，使肠壁的 10-15cm 明显缺血。我们将动物随机分为接受纤维蛋白贴片覆盖吻合口的组（病例组）或不覆盖的组（对照组）。我们报告了实验模型中组织对缺氧反应相关蛋白的免疫组化表达变化。我们的结果表明，纤维蛋白贴片延迟了愈合反应，在手术床中促进了更长时间的炎症。然而，纤维蛋白贴片在临床上减少裂开的有效性表明，这种延迟不会对患者的结果产生负面影响。影响声明吻合口失败对患者的后果是巨大的。了解越来越多的纤维蛋白密封剂的使用如何与组织和愈合过程相互作用，有助于证明其使用的合理性，并鼓励研究如何进一步提高这种效果。我们认为，目前的工作表明，该贴片可以通过比单纯的肠内固定和物理支撑更复杂的机制来改善愈合。此外，还需要进一步的研究来证实我们的初步发现。
