Surgical management of severe bevacizumab-induced ischemic pancolitis

H. L. Chan, I. Rotas, F. Pugin, B. Egger

Objective

Bevacizumab is a murine‐anti‐human monoclonal antibody directed against vascular endothelial growth factor‐A, which disrupts endothelial cell survival mechanisms and the development of new tumour blood supply. Bevacizumab has been shown to prolong survival of patients with metastatic colorectal cancer when combined with chemotherapy. Serious adverse effects have been reported. We report here a case of bevacizumab-induced ischemic pancolitis and its surgical management.

Methods

A 56-year-old male patient with a rectal cancer (cT2N2M0) underwent neoadjuvant chemoradiotherapy followed by restorative low anterior resection with total mesorectal excision and protective ileostomy. Following that adjuvant chemotherapy (FOLFOX) was administered. In the follow-up the patient developed lung metastases and underwent chemotherapy with FOLFIRI and Bevacizumab (Avastin®). Due to progression of the disease, a second-line chemotherapy (Irinotecan, 5-Fluorouracil) was added for 6 months. During this last treatment, the patient was admitted to our emergency department with abdominal pain and vomiting. Physical examination revealed a diffuse peritonitis and CT-scan showed free intraabdominal fluid but no free air. At emergency laparotomy a massive necrotizing pancolitis was found. Total colonic resection with terminal ileostomy and an ultra-short Hartmann stump was performed.

Results

Histopathology confirmed the diagnosis with multiple fibrous thrombi present in the submucosa and an extended transmural inflammation. These histological findings were consistent with a bevacizumab-induced ischemic colitis. Follow-up was completely uneventful and the patient was discharged home 13 days later.

Conclusion

Side effects of bevacizumab are hypertension, proteinuria, arterial thrombosis, minor bleeding events and delayed wound healing. Furthermore, gastrointestinal perforation has been observed in up to 2%. However, extensive colonic ischemia seems to be an extremely rare complication. The mechanism is unclear and believed to be associated with the inhibition of vascular endothelium growth factor leading to thrombosis of smaller splanchnic vessels. In conclusion, bevacizumab-induced ischemic pancolitis is a rare but very serious complication and surgery needs to be applied before perforation occurs.