Antiangiogenic agents and late anastomotic complications

Anticancer agents targeting circulating vascular endothelial growth factor (VEGF) (e.g., bevacizumab and aflibercept) are strong angiogenesis inhibitors. As such, they may hamper the healing process, notably in the early postoperative period. Whether antiangiogenic agents may be associated with late postoperative healing complications is less known. We reviewed three cases of patients with anastomotic complications under antiangiogenic treatment occurring more than 1 year after initial surgery and we conducted a review of the literature. We report the first case of delayed anastomotic leakage which occurred under aflibercept therapy 13 months after a bilioenteric anastomosis and two cases of delayed rectal anastomotic complications associated with bevacizumab treatment 18 and 78 months after surgery. Fifteen similar cases of late gastrointestinal anastomotic complications were found in the English literature. Antiangiogenic agents are probably not deleterious to a healed wound. However, they appear to be associated with an increased risk of complications in a subgroup of patients. According to the 18 cases reported, the main risk factors appear to be low anterior resection for rectal cancer, perioperative radiotherapy, and early postoperative leak which heals through the formation of abundant and hypervascularized granulation tissue.