Antiangiogenic agents and late anastomotic complications

Abstract

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.

Physiologie der Anastomosenheilung

“…[8]. Das zeigt, dass der Prozess der Neoangiogenese bei vollständig erholter mechanischer Stabilität der Anastomose noch relativ lange von großer Bedeutung ist.…”

Extremely late wound dehiscence following bevazicumab treatment in a long term survival glioblastoma patient

“…In contract, Deshaies et al [4] reported on 18 cases of unusually delayed anastomotic complications in patients receiving bevacizumab after gastrointestinal surgery with the anastomotic complication occurring between 3 and 78 months after surgery (mean, 18 months). This data supports our report of 41 months between surgery and wound dehiscence.…”

Intraperitoneal Administration of Bevacizumab Intraoperatively Does Not Affect Abdominal Wound Healing in Rats

“…Recently, a single case of Fournier gangrene in a man during bevacizumab treatment has been reported; it happened 4 months after chemotherapy with 5-fluorouracil/leucovorin/oxaliplatin for advanced colorectal cancer [40]. In a review of the literature, late anastomotic complications attributable to the use of anti-angiogenetic agents amounted altogether to 18 cases [16]. It is noteworthy that they happened very late, >12 or even 78 months after treatment with bevacizumab.…”

“…Despite few recommendations for its administration 6 weeks before or 4 weeks after surgery [9,10], there is still no clear evidence in current clinical practice with respect to the optimal administration time point. On the other hand, in a few studies, complications attributed to bevacizumab administration [11,12,13,14,15] have been reported in cancer patients, especially late anastomotic complications [16]. In an experimental setting, only studies investigating the effect of locally applied bevacizumab on corneal wound healing in rats, mice and rabbits have been reported [17,18,19,20,21], although with conflicting results.…”