[Surgical management of bevacizumab-associated peritonitis due to perforation].
BACKGROUND
Bevacizumab (Avastin, Fa. Roche, Genentech) is the first anti-angiogenic agent to be approved for the routine clinical treatment of cancer. Its toxicity profile is different to that of standard chemotherapeutic substances. Despite the rarity of gastrointestinal (GI) perforation in patients treated with bevacizumab, this serious adverse event results in significant morbidity and mortality. It was the aim of this study, based on exemplary cases of the reporting clinic as well as on published experiences, to characterise the specific clinical findings, the extraordinary pathogenesis, and the therapeutic outcome of such cases of peritonitis caused by perforation after antibody treatment.


METHODS
Data of all patients with perforation-caused peritonitis due to bevacizumab therapy since its clinical inauguration were sought in i) the database of the reporting clinic (case series), ii) in the published literature for comparison (historical comparative group) and iii) analysed with regard to results of the surgical management (evaluated parameters: rate of anastomotic insufficiency / disturbances of wound healing, morbidity, mortality).


RESULTS
Over a time period of 4 years (from 2 / 1 / 2004 to 1 / 31 / 2008), overall 15 patients were found in this study, among whom 4 patients came from the reporting clinic (mean age, 57 years; males : females = 2 : 2). The mean duration of antibody (Ab) treatment until occurrence of the complication was 70 days (range: 8-150 days). Thirteen patients underwent surgical intervention, 2 patients died due to severe peritonitis without any operation. The overall morbidity was 73.3 % (n = 11 / 15), the mortality was 33.3 % (n = 5 / 15). All patients with an anastomosis developed an anastomotic insufficiency (100 %). Wound healing complications occurred in 38.5 % of the subjects (n = 5 / 13).


CONCLUSIONS
Peritonitis after GI perforation due to bevacizumab-based Ab treatment needs to be considered as a rare but serious and life-threatening complication. Impairment of wound healing because of the inhibition of angiogenesis is the reason for a different management of GI perforation under these conditions compared with the standard surgical treatment of peritonitis of other causes. In particular, it is recommended to avoid primary anastomosis and to prefer application of an intestinal stoma.
Kube
R
R
Klinik für Allgemein-, Viszeral- und Gefässchirurgie, Universitätsklinikum A. ö. R., Leipziger Strasse 44, Magdeburg, Germany. rainer.kube@med.ovgu.de
Meyer
F
F
Bien
N
N
Schmidt
C
C
Mroczkowski
P
P
Dalicho
S
S
Lippert
H
H
D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy; D002283:Carcinoma, Bronchogenic / Q000188:drug therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D016022:Case-Control Studies; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007081:Ileostomy; D007416:Intestinal Perforation / Q000139:chemically induced* / Q000601:surgery*; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010538:Peritonitis / Q000139:chemically induced* / Q000601:surgery*; D011183:Postoperative Complications / Q000139:chemically induced / Q000401:mortality / Q000601:surgery; D012004:Rectal Neoplasms / Q000188:drug therapy; D013529:Surgical Wound Dehiscence / Q000139:chemically induced / Q000401:mortality / Q000601:surgery; D015996:Survival Rate; D014945:Wound Healing / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab