title: Pharmacological interventions for improved colonic anastomotic healing: a meta-analysis.
abstract: OBJECTIVE
  To identify pharmaceuticals for the prophylaxis of anastomotic leakage (AL), we systematically reviewed studies on anastomosis repair after colorectal surgery.
  
  
  METHODS
  We searched PubMed and EMBASE for articles published between January 1975 and December 2012. We included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. We excluded studies on adverse events from interventions, nutritional interventions or in situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. We performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with P < 0.05.
  
  
  RESULTS
  Of the 56 different therapeutic agents assessed, 7 met our inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95%CI: 30-89) vs the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95%CI: 4-53) vs the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95%CI: 14-76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95%CI: 7-35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95%CI: 43-79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95%CI: 13-34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95%CI: 31-66) on postoperative days 3-4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7%) compared with the 113 placebo-treated patients (9.7%).
  
  
  CONCLUSIONS
  This systematic review identified only one randomized clinical trial and seven therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery.
authors.affiliation: Mari Nanna Øines, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus Sven Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: Mari Nanna
authors.initials: MN
authors.lastname: Oines
authors.affiliation: Mari Nanna Øines, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus Sven Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: Peter-Martin
authors.initials: PM
authors.lastname: Krarup
authors.affiliation: Mari Nanna Øines, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus Sven Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: Lars Nannestad
authors.initials: LN
authors.lastname: Jorgensen
authors.affiliation: Mari Nanna Øines, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus Sven Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark.
authors.forename: Magnus Sven
authors.initials: MS
authors.lastname: Agren
mesh_terms: D000714:Anastomosis, Surgical; D057868:Anastomotic Leak / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D016009:Chi-Square Distribution; D003082:Colectomy / Q000009:adverse effects; D003106:Colon / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D023421:Models, Animal; D012007:Rectum / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D005765:Gastrointestinal Agents
keywords: Anastomotic healing; Breaking strength; Bursting pressure; Collagen; Colorectal surgery; Experimental; Meta-analysis