eP648 - Extracellular Matrix Hydrogel Reduces Leak Rates in a Rodent Model of a Low Rectal Anastomosis

Purpose/Background: Anastomotic leaks are a dreaded source of morbidity following rectosigmoid resections. Improved management of rectal cancer has resulted in increased rates of sphincter preserving surgeries; however, rates of rectal anastomotic leak remain high. A sufficient reduction in leak rates could obviate the need for routine prophylactic fecal diversion. Extracellular matrix (ECM) derived surgical devices can augment healing in gastrointestinal applications. Urinary bladder matrix (UBM) is a highly adaptable form of acellular ECM that promotes constructive remodeling but has not been evaluated in colorectal anastomoses. A lack of reliable small animal models for colorectal anastomotic leak impedes product development. We aimed to create a reproducible rat model of a distal colorectal resection to evaluate the efficacy of ECM adjuncts in reducing anastomotic leaks and to study mechanisms involved in anastomotic healing over time.Methods/Interventions: Female Sprague-Dawley rats underwent standardized distal colonic resections and sutured anastomoses below the peritoneal reflection. Rats were randomly assigned to control, UBM extraluminal wraps, or UBM hydrogel application after anastomotic creation. In the initial experiments, blinded necropsy was performed on post-operative day 7 with a multimodal assessment of anastomotic leak. The perianastomotic tissue underwent a comprehensive histologic assessment to evaluate the quality of healing. Further experiments compared control animals to intraluminal UBM hydrogel treated animals over a series of timepoints (days 1, 3, 5, 14, 28, 56).Results/Outcomes: Anastomotic leaks reliably occurred in 46% of control animals with a significantly lower leak rate of 8% in UBM hydrogel treated rats on post-operative day 7 (Table 1). UBM extraluminal wraps did not result in a reduction of anastomotic leaks. Fewer perianastomotic adhesions were seen in animals receiving hydrogel treatment. Histologic evaluation demonstrated significant improvements in composite healing scores for anastomoses treated with the hydrogel. Improved anastomotic healing was demonstrated throughout the series of timepoints in anastomoses that received intraluminal hydrogel applications.Conclusion/

Discussion: This small animal model of a low rectal anastomosis presents a dependable platform for surgical device testing. UBM hydrogel demonstrates promise as an adjunct to reduce rectal anastomotic leak rates via mechanical and biochemical effects. Multimodal evaluation of anastomotic healing over time provides insight into mechanisms involved in anastomotic leaks and pathways to reduce leak rates.Table 1Outcomes of control and UBM hydrogel treated animals on post-operative day 7