Syracuse

Anastomotic leak occurrence is a severe complication after colorectal surgery. Considering the difficulty of treating these leaks and their impact on patient care, there is a strong need for an efficient prevention strategy. We evaluated a combination of extracellular vesicles (EVs) from rat adiposederived stromal cells with a thermoresponsive gel, Pluronic® F127 (PF-127) to prevent anastomotic leaks. The pro-regenerative and immunomodulatory potencies of EVs are assessed in vitro. In vivo efficacy are assessed in rat with a colonic anastomosis model after irradiation. Endoscopic, anatomical and histological data show a consistent effect of EVs + gel on the healing of colonic anastomosis. These results are illustrated by a smaller anastomotic ulcer size, less fibrosis and less inflammatory infiltrations in the EVs + gel group. This multi-modal investigation is the first to point-out the translational potential of EVs combined with PF-127 for the healing of high-risk colorectal anastomosis.

The incidence of rectal cancer worldwide is 732,210 per year 1 . Neoadjuvant chemoradiotherapy supplemented by surgery with a low colorectal or colo-anal anastomosis is recommended in locally advanced disease 2 . Despite years of research, the incidence of anastomotic leak after rectal surgery remains high, ranging from 3 to 21% 3,4 and is associated with increased morbidity, mortality, and cancer recurrence 5 . Furthermore, anastomotic leaks are associated with an increased healthcare burden due to the higher costs of management and the use of resources for remedial care 6 . It is known that anastomotic leak etiology is multifactorial. Excluding technical failures, there is accumulating evidence pointing at anastomotic leak as the result of a complex, dynamic interplay of several factors and biological processes 7-9 . This includes host genetics, gut microbiome, inflammation, and the immune system 10 . The occurrence of anastomotic leak might also be linked to TNM stage and patient nutritional status 11 , along with treatment-related factors. Indeed, while preoperative chemoradiotherapy for rectal cancer improves local