Systematic review Systematic review of experimental studies on intestinal anastomosis S. T. K. Yauw 1 , K. E. Wever 1,2 , A. Hoesseini 1 , M. Ritskes-Hoitinga 2 and H. van Goor 1 1 Department of Surgery, Radboud University Medical Centre, and 2 Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Central Animal Laboratory, Radboud University, Nijmegen, The Netherlands Correspondence to: Mr S. T. K. Yauw, Radboud University Medical Centre, Department of Surgery, Geert-Grooteplein zuid 10, Internal Post 618, 6525 GA Nijmegen, The Netherlands (e-mail: simon.yauw@radboudumc.nl) Background: The contribution of animal research to a reduction in clinical intestinal anastomotic leakage is unknown, despite numerous experimental studies. In view of the current societal call to replace, reduce and refne animal experiments, this study examined the quality of animal research related to anastomotic healing and leakage. Methods: Animal studies on intestinal anastomotic healing were retrieved systematically from PubMed and Embase. Study objective, conclusion and animal model were recorded. Reporting quality and internal validity (reporting of randomization and blinding) were assessed. Results: A total of 1342 studies were identifed, with a rising publication rate. The objectives of most studies were therapeutic interventions (64⋅8 per cent) and identifcation of risk factors (27⋅5 per cent). Of 350 articles studying experimental therapies, 298 (85⋅1 per cent) reported a positive effect on anastomotic healing. On average, 44⋅7 per cent of relevant study characteristics were not reported, in particular details on anastomotic complications (31⋅6 per cent), use of antibiotics (75⋅7 per cent), sterile surgery (83⋅4 per cent) and postoperative analgesia (91⋅4 per cent). The proportion of studies with randomization, blinding of surgery and blinding of primary outcome assessment has increased in the past two decades but remains insuffcient, being included in only 62⋅4, 4⋅9 and 8⋅5 per cent of publications respectively. Animal models varied widely in terms of species, method to compromise healing, intestinal segment and outcome measures used. Conclusion: Animal research on anastomotic leakage is of poor quality and still increasing, contrary to societal aims. Reporting and study quality must improve if results are to impact on patients. Presented in part to the Tenth Academic Surgical Congress of the Society of University Surgeons and Association for Academic Surgery, Las Vegas, Nevada, USA, February 2015 Paper accepted 18 December 2014 Published online 2 April 2015 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9776 Introduction Worldwide, intestinal resection and anastomosis are per- formed annually in over a million people with colorectal cancer, infammatory bowel disease, complicated diverti- culitis and morbid obesity 1 – 3 . Despite improvements in technique, anastomotic devices and perioperative care, an intestinal anastomosis has a 3 – 14 per cent risk of leakage 4,5 . This postoperative complication often results in severe morbidity, with a consequent mortality rate of up to 18 per cent 6 – 8 . Many risk factors have been identifed from clinical studies 4,9 . Male sex, low colorectal anastomosis, preoperative chemoradiation, advanced tumour stage, immunosuppression, perioperative bleeding and multiple staple frings have all been associated with increased leak rates 4,9,10 . Animal models have been used extensively to study cau- sality and underlying pathophysiological mechanisms 11,12 , as well as the assessment of techniques and products that reinforce the anastomosis or improve healing 13,14 . The study of anastomotic failure in animals involves moderate to severe animal discomfort, dedicated human effort and considerable cost. This has led to a European directive that animal experiments need to be replaced, reduced and refned whenever possible 15,16 . Owing to its complex physiology, the process of anastomotic healing is presently considered too complicated to mimic in vitro. To reduce © 2015 BJS Society Ltd BJS 2015; 102: 726–734 Published by John Wiley & Sons Ltd