title: The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease: a systematic review.
abstract: BACKGROUND
  Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.
  
  
  OBJECTIVE
  We assessed the effect of anti-tumor necrosis factor alpha on postoperative complications in patients with Crohn's disease undergoing abdominal surgery.
  
  
  METHODS
  Studies were identified through electronic and manual searches.
  
  
  METHODS
  Observational studies on patients with Crohn's disease undergoing laparoscopic or open abdominal surgery were included.
  
  
  METHODS
  Anti-tumor necrosis factor alpha agents were administered within 3 months before surgery.
  
  
  METHODS
  The primary outcome was anastomotic complications including overt dehiscence, intra-abdominal abscess, and enteric fistulas.
  
  
  RESULTS
  Fourteen studies on 679 patients in the intervention (anti-tumor necrosis factor alpha) group and 2363 controls were included. Random-effects meta-analysis found no difference in anastomotic complications between the 2 groups (7.6% versus 8.2%; risk ratio, 0.91; 95% CI, 0.56-1.48). There was clear heterogeneity between studies. In subgroup analyses, the anti-tumor necrosis factor alpha increased anastomotic complications in trials with a lower risk of bias, but not in the studies with a higher bias risk (risk ratio, 1.63; 95% CI, 1.03-2.60 and risk ratio, 0.17; 95% CI, 0.05-0.60). In the overall analysis and in studies with a lower bias risk, anti-tumor necrosis factor alpha agents increased the risk of nonanastomotic surgical complications, major medical complications, and minor medical complications.
  
  
  CONCLUSIONS
  Limitations of observations studies.
  
  
  CONCLUSIONS
  In studies with a low risk of bias, anti-tumor necrosis factor alpha agents increased the risk of anastomotic complications. Inadequate bias control may lead to an underestimated risk of anastomotic complications.
authors.affiliation: 1Department of Surgery, Slagelse Hospital, Slagelse, Denmark 2Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark 3Department of Surgery, Holbaek Hospital, University of Copenhagen, Copenhagen, Denmark 4Gastrounit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Hussuna
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.forename: Gunnar
authors.initials: G
authors.lastname: Olaison
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.forename: Lise L
authors.initials: LL
authors.lastname: Gluud
mesh_terms: D018784:Abdominal Abscess / Q000209:etiology; D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000209:etiology; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D007412:Intestinal Fistula / Q000209:etiology; D007422:Intestines / Q000601:surgery*; D011183:Postoperative Complications / Q000209:etiology* / Q000276:immunology; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014945:Wound Healing / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha