Emma Children's Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands.
Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
BJS Open. 2023 Sep 5;7(5). doi: 10.1093/bjsopen/zrad099.
Understanding the early processes underlying intestinal anastomotic healing is crucial to comprehend the pathophysiology of anastomotic leakage. The aim of this study was to assess normal intestinal anastomotic healing and disturbed healing in rats to investigate morphological, cellular and intrinsic molecular changes in the anastomotic tissue.
Anastomoses were created in two groups of Wistar rats, using four sutures or 12 sutures to mimic anastomotic leakage and anastomotic healing respectively. At 6, 12, 24 hours and 2, 3, 5 and 7 days, anastomotic tissue was assessed macroscopically using the anastomotic complication score and histologically using the modified Ehrlich-Hunt score. Transcriptome analysis was performed to assess differences between anastomotic leakage and anastomotic healing at the first three time points to find affected genes and biological processes.
Ninety-eight rats were operated on (49 animals in the anastomotic leakage and 49 in the anastomotic healing group) and seven rats analysed at each time point. None of the animals with 12 sutures developed anastomotic leakage macroscopically, whereas 35 of the 49 animals with four sutures developed anastomotic leakage. Histological analysis showed increasing influx of inflammatory cells up to 3 days in anastomotic healing and up to 7 days in anastomotic leakage, and this increase was significantly higher in anastomotic leakage at 5 (P = 0.041) and 7 days (P = 0.003). Transcriptome analyses revealed large differences between anastomotic leakage and anastomotic healing at 6 and 24 hours, mainly driven by an overall downregulation of genes in anastomotic leakage.
Transcriptomic analyses revealed large differences between normal and disturbed healing at 6 hours after surgery, which might eventually serve as early-onset biomarkers for anastomotic leakage.
了解肠吻合口愈合的早期过程对于理解吻合口漏的病理生理学至关重要。本研究旨在评估大鼠正常肠吻合口愈合和受损愈合，以研究吻合组织的形态学、细胞学和内在分子变化。
使用 4 针或 12 针缝线分别模拟吻合口漏和吻合口愈合，在两组 Wistar 大鼠中创建吻合口。在 6、12、24 小时以及 2、3、5 和 7 天时，使用吻合口并发症评分和改良 Ehrlich-Hunt 评分分别从宏观和组织学角度评估吻合组织。在最初的三个时间点进行转录组分析，以评估吻合口漏和吻合口愈合之间的差异，寻找受影响的基因和生物学过程。
98 只大鼠接受了手术（吻合口漏组 49 只，吻合口愈合组 49 只），每个时间点分析了 7 只大鼠。用 12 针缝线的 49 只大鼠中无一例出现肉眼吻合口漏，而用 4 针缝线的 49 只大鼠中有 35 例出现吻合口漏。组织学分析显示，在吻合口愈合中，炎症细胞的流入量增加至 3 天，在吻合口漏中增加至 7 天，在吻合口漏中，在第 5 天（P = 0.041）和第 7 天（P = 0.003）增加更为显著。转录组分析显示，在手术后 6 小时和 24 小时，吻合口漏和吻合口愈合之间存在显著差异，主要是吻合口漏中基因的整体下调。
转录组分析显示，手术后 6 小时正常和受损愈合之间存在显著差异，这可能最终成为吻合口漏的早期生物标志物。
