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

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.

Enhancing intestinal anastomotic healing using butyrate: Systematic review and meta-analysis of experimental animal studies.

BACKGROUND: Despite advancements in surgical technique and perioperative care, intestinal anastomoses still have a 10-15 per cent risk of leakage, which results in considerable morbidity and/or mortality. Recent animal studies have suggested that administration of butyrate to the anastomotic site results in enhanced anastomotic strength, which may prevent leakage. This systematic review and meta-analysis summarises current evidence concerning the effect of butyrate administration on anastomotic healing and will form a scientific basis for the development of new research into this subject. METHODS: Animal studies on the effect of butyrate-based interventions in models of intestinal anastomotic healing were systematically retrieved from online databases. Bibliographical data, study characteristics and outcome data were extracted, and internal validity of the studies was assessed. Outcomes studied through meta-analysis concerned: anastomotic strength, anastomotic leakage, collagen metabolism and general histologic parameters of wound healing. RESULTS: A comprehensive search and selection identified 19 relevant studies containing 41 individual comparisons. Design and conduct of most experiments were poorly reported resulting in an unclear risk of bias. Meta-analyses showed that butyrate administration significantly increases anastomotic strength (SMD 1.24, 0.88 to 1.61), collagen synthesis (SMD 1.44, 0.72 to 2.15) and collagen maturation, making anastomoses less prone to leakage in the early postoperative period (OR 0.37, 0.15 to 0.93). CONCLUSION: This systematic review and meta-analysis shows that there is potential ground to investigate the use of butyrate in clinical trials to prevent anastomotic leakage in intestinal surgery. However, more research is necessary to define the best application form, dosage and administration route.