Abstract
BackgroundDisturbance of intestinal wound closure leads to insufficient anastomotic healing and is associated with considerable morbidity following colorectal resections. Matrix metalloproteinases (MMPs) play a crucial role in regulation of wound closure. Here fluorescence endoscopy was evaluated for assessment of MMP-2/-9 expression during failed intestinal anastomotic healing.MethodsDistal colonic anastomoses were performed as a model for disturbed healing in 36 Balb/c mice. Healing was evaluated endoscopically, macroscopically, and histologically after 1, 3 and 5 days. For detection of MMP-2/-9 expression fluorescence endoscopy (FE) was used following i.v.-administration of a Cy5.5-labeled MMP-2/-9 specific tracer. FE was complemented by quantification of the fluorescence signal using the MS-FX PRO Optical Imaging System. An overall leakage score was calculated and correlated with the results of FE.ResultsWith increasing incidence of anastomotic leakage from POD1 (17%) to POD5 (83%) the uptake of the MMP tracer gradually increased (signal-to-noise ratio (SNR), POD1: 17.91 ± 1.251 vs. POD3: 30.56 ± 3.03 vs. POD5: 44.8 ± 4.473, P<0.0001). Mice with defective anastomotic healing showed significantly higher uptake compared to non-defective (SNR: 37.37± 3.63 vs. 26.16± 3.635, P = 0.0369). White light endoscopy and FE allowed evaluation of anastomotic healing and visualization of mucosal MMPs in vivo. Using FE based detection of MMPs in the anastomosis, an overall positive predictive value of 71.4% and negative predictive value of 66.6% was calculated for detection of anastomotic leakage.ConclusionDuring disturbed anastomotic healing increased expression of MMP-2/-9 was observed in the anastomotic tissue. Fluorescence endoscopy for detection of MMP-2/-9 during the healing process might be a promising tool for early identification of anastomotic leakage.
Highlights
Anastomotic healing following colorectal resections is a tightly balanced process that is influenced by a plethora of cellular and non-cellular mediators [1]
In support of the model, on POD1 none of the anastomoses reached a top score of 6 pts, whereas on POD5 50% of the anastomoses were scored with maximum points indicating increasing leakage rates
Evaluation of fluorescence endoscopy for detection of anastomotic leakage After we have shown that the tracer could be used for detection of Matrix metalloproteinases (MMPs) Expression in the tissue and well correlated with development of anastomotic leakage, we investigated whether the probe could be used for MMP detection by means of fluorescence endoscopy
Summary
Anastomotic healing following colorectal resections is a tightly balanced process that is influenced by a plethora of cellular and non-cellular mediators [1]. The healing process can be influenced by patient specific factors such as the inflammatory condition of the tissue as well as treatment related factors such as immune suppression due to preoperative chemotherapy or radiation [2, 3]. Considering the significant impact on morbidity and mortality associated with its development, anastomotic leakage can be regarded as the major complication following colorectal resections [10, 11]. Disturbance of intestinal wound closure leads to insufficient anastomotic healing and is associated with considerable morbidity following colorectal resections. Fluorescence endoscopy was evaluated for assessment of MMP-2/-9 expression during failed intestinal anastomotic healing
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