Postoperative morbidity and perioperative anti-TNF treatment: should we blame the drugs?

C onflicting data regarding the use of anti-tumor necrosis factor (TNF) and postoperative morbidity in Crohn’s disease (CD) have been published. Appau et al showed a significant increase in anastomotic leakage (10.0% vs. 4.3%) resulting in a significant increased likelihood for sepsis (odds ratio [OR] 2.32; 95% confidence interval [CI] 1.12–4.82) and reoperation (OR 2.90; 95% CI 0.95–8.81) after elective ileocecal resection for CD in patients pretreated with infliximab. This urged the surgeons from Mayo Clinic Rochester to audit their results of resectional surgery. In a time period of 4 years, 444 patients underwent abdominal surgery and 370 patients were eligible for analysis. Patients were categorized for the perioperative use of anti-TNF agents (infliximab, adalimumab, and certolizumab pegol). This was defined as anti-TNF treatment within 8 weeks preoperatively or within 4 weeks postoperatively. The two groups (n 1⁄4 119, anti-TNF group; n 1⁄4 251, non-anti-TNF group) matched fairly well, although the patients in the anti-TNF group had more severe disease and the non-anti-TNF group received more steroid therapy. No difference was found for the overall 30-day postoperative complication rate for the entire study group (about 30%). Age and ASA score were predictors for increased morbidity in a univariate analysis. Furthermore, there was no difference in intraabdominal infectious complications (abscesses and anastomotic leaks) in either group (1.99% in the anti-TNF group and 3.66% in the control group, P 1⁄4 0.44). The overall rate of intraabdominal complications was 2.4%. The authors therefore concluded that no association between perioperative anti-TNF therapy and postoperative complications was found and as a result they do not recommend delaying surgery in patients who received preoperative anti-TNF treatment. The biological antibodies targeting TNF-a have proven their efficacy both as agents for induction as well as for maintenance of remission. TNF-a is a key proinflammatory cytokine that plays a role in regulating cells primordial for wound healing. The impact of anti-TNF drugs on postoperative morbidity is therefore a relevant question. In the past, steroids have been shown to have a negative dose-dependent impact on the postoperative course, leading to the practice of tapering steroids before surgery. The data from Mayo are important but have some shortcomings: despite the number of patients included, the study has a suboptimal design, being monocentric and retrospective. The study is underpowered to incorporate all potential confounders in a multivariate mode. Furthermore, no details are given on the proportion of patients who received Infliximab only after surgery, one could presume that those patients would have no postoperative septic complications. On the other hand, the low anastomotic leak rate (overall 2.4%) sets a new benchmark and underlines the actual safety of surgery achieved in a tertiary referral center. A multidisciplinary approach is essential to provide optimal care for most inflammatory bowel disease patients: this will avoid protracted medical treatment leading to further clinical deterioration of the patient (poor nutritional state and low serum albumin, undrained abdominal sepsis, and intestinal occlusion), which increases postoperative morbidity. Surgeons should closely monitor and document postoperative morbidity in a more standardized way to allow more meaningful recommendation and to define high-risk patients for anastomotic leakage.