Histology and transcriptome insights into the early processes of intestinal anastomotic healing: a rat model.


Journal

BJS open
ISSN: 2474-9842
Titre abrégé: BJS Open
Pays: England
ID NLM: 101722685

Informations de publication

Date de publication:
05 09 2023
Historique:
received: 03 05 2023
revised: 24 07 2023
accepted: 22 08 2023
medline: 23 10 2023
pubmed: 19 10 2023
entrez: 19 10 2023
Statut: ppublish

Résumé

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.

Sections du résumé

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.

Identifiants

pubmed: 37855751
pii: 7321968
doi: 10.1093/bjsopen/zrad099
pmc: PMC10586197
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.

Références

World J Gastroenterol. 2007 Jul 21;13(27):3721-5
pubmed: 17659732
J Gastrointest Surg. 2020 Sep;24(9):2160-2166
pubmed: 32524361
Am J Surg. 1992 Jan;163(1):71-7
pubmed: 1733376
Microsurgery. 2006;26(3):131-6
pubmed: 16518804
Sci Transl Med. 2015 May 6;7(286):286ra68
pubmed: 25947163
Br J Surg. 2017 Apr;104(5):503-512
pubmed: 28295255
J Surg Res. 1993 Sep;55(3):256-60
pubmed: 8412107
JAMA Surg. 2013 Feb;148(2):190-201
pubmed: 23426599
Surg Oncol. 2022 Mar;40:101708
pubmed: 35092916
Int J Mol Sci. 2017 May 11;18(5):
pubmed: 28492497
Colorectal Dis. 2017 Jan;19(1):O1-O12
pubmed: 27671222
J Exp Med. 2009 Jul 6;206(7):1465-72
pubmed: 19564350
Ann Surg. 2017 Mar;265(3):547-554
pubmed: 27070935
Br J Surg. 2017 Apr;104(5):619-630
pubmed: 28195642
Genome Biol. 2014;15(12):550
pubmed: 25516281
Physiol Rev. 2019 Jan 1;99(1):665-706
pubmed: 30475656
Surg Clin North Am. 1997 Jun;77(3):549-73
pubmed: 9194880
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
BMC Gastroenterol. 2015 Dec 21;15:180
pubmed: 26691961
Int J Colorectal Dis. 2009 May;24(5):569-76
pubmed: 19221768
Bioinformatics. 2016 Oct 1;32(19):3047-8
pubmed: 27312411
Genome Biol. 2004;5(10):R80
pubmed: 15461798
Mucosal Immunol. 2009 Sep;2(5):403-11
pubmed: 19587639
Dis Colon Rectum. 2018 Nov;61(11):1258-1266
pubmed: 30239395
J Surg Res. 2009 Jul;155(1):7-12
pubmed: 19446852
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cells. 2021 Dec 25;11(1):
pubmed: 35011620
J Gastrointest Surg. 2013 Sep;17(9):1698-707
pubmed: 23690209
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Int J Colorectal Dis. 2016 May;31(5):1021-1030
pubmed: 26960997
PLoS Biol. 2020 Jul 14;18(7):e3000410
pubmed: 32663219

Auteurs

Claire P M van Helsdingen (CPM)

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.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Amsterdam Reproduction and Development, Amsterdam, The Netherlands.

Aurelia C L Wildeboer (ACL)

Emma Children's Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands.
GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.

Konstantina Zafeiropoulou (K)

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.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.

Audrey C H M Jongen (ACHM)

Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Joanna W A M Bosmans (JWAM)

Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.

Camille Gallé (C)

Department of General Surgery, Maastricht University, Maastricht, The Netherlands.

Theodorus B M Hakvoort (TBM)

Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.

Marion J J Gijbels (MJJ)

Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Medical Biochemistry, Amsterdam UMC, location University of Amsterdam, Experimental Vascular Biology, Amsterdam, The Netherlands.
Amsterdam Infection and Immunity, Amsterdam, The Netherlands.
Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.

Wouter J de Jonge (WJ)

Amsterdan UMC, location University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Department of Surgery, University of Bonn, Bonn, Germany.

Nicole D Bouvy (ND)

Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.

Andrew Y F Li Yim (AYF)

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.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Amsterdam Reproduction and Development, Amsterdam, The Netherlands.
Department of Human Genetics, Amsterdam UMC, location University of Amsterdam, Genome Diagnostics Laboratory, Amsterdam, The Netherlands.

Joep P M Derikx (JPM)

Emma Children's Hospital, Amsterdam UMC, location University of Amsterdam, Paediatric Surgery, Amsterdam, The Netherlands.
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
Amsterdam Reproduction and Development, Amsterdam, The Netherlands.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH