TY - JOUR
T1 - Histology and transcriptome insights into the early processes of intestinal anastomotic healing
T2 - a rat model
AU - Van Helsdingen, Claire P.M.
AU - Wildeboer, Aurelia C.L.
AU - Zafeiropoulou, Konstantina
AU - Jongen, Audrey C.H.M.
AU - Bosmans, Joanna W.A.M.
AU - Gallé, Camille
AU - Hakvoort, Theodorus B.M.
AU - Gijbels, Marion J.J.
AU - De Jonge, Wouter J.
AU - Bouvy, Nicole D.
AU - Li Yim, Andrew Y.F.
AU - Derikx, Joep P.M.
N1 - Funding Information:
This work was supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) research programme VIDI with project number 016.196.343. Acknowledgements
Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of BJS Society Ltd.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Background: 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. Method: 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. Results: 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. Conclusion: 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.
AB - Background: 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. Method: 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. Results: 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. Conclusion: 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.
U2 - 10.1093/bjsopen/zrad099
DO - 10.1093/bjsopen/zrad099
M3 - Article
SN - 2474-9842
VL - 7
JO - BJS Open
JF - BJS Open
IS - 5
M1 - zrad099
ER -