Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. May 27, 2016; 8(5): 389-401
Published online May 27, 2016. doi: 10.4240/wjgs.v8.i5.389
Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review
Malene Nerstrøm, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus S Ågren
Malene Nerstrøm, Peter-Martin Krarup, Lars Nannestad Jorgensen, Magnus S Ågren, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
Magnus S Ågren, Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, DK-2400 Copenhagen NV, Denmark
Magnus S Ågren, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
Author contributions: Nerstrøm M performed the literature search, collected and analyzed the data and drafted the article; Krarup PM designed the study, performed the literature search and the statistical analyses; Jorgensen LN designed the study and edited the manuscript; Ågren MS designed the study and edited the manuscript.
Conflict-of-interest statement: There are no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Magnus S Ågren, Professor, Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. magnus.agren@mail.dk
Telephone: +45-35316493 Fax: +45-35313911
Received: June 28, 2015
Peer-review started: July 5, 2015
First decision: September 17, 2015
Revised: February 8, 2016
Accepted: March 4, 2016
Article in press: March 9, 2016
Published online: May 27, 2016
Processing time: 323 Days and 23.6 Hours
Abstract

AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions.

METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of improving anastomotic healing in the colon or rectum under complicated preoperative and/or intraoperative conditions were included. We excluded studies investigating the adverse effects or risk assessment of an active intervention. Furthermore, investigations of biophysical materials, sealants, electrical stimulation and nutrients were excluded. The primary study outcome was biomechanical anastomotic strength or AL. The meta-analysis focused on therapeutic agents that were investigated in one animal model using the same outcome by at least three independent research groups.

RESULTS: The 65 studies included were divided into 7 different complicated animal models: Bowel ischemia, ischemia/reperfusion, bowel obstruction, obstructive jaundice, peritonitis, chemotherapy and radiotherapy. In total, 48 different therapeutic compounds were examined. The majority of investigated agents (65%) were reported as beneficial for anastomotic healing. Twelve of the agents (25%) were tested more than once in the same model, whereas 13 (27%) of the agents were tested in two or more models of complicated healing. Two therapeutic agents met our inclusion criteria for the meta-analysis. Postoperative hyperbaric oxygen therapy significantly increased anastomotic bursting pressure in ischemic colon anastomoses by a mean of 28 mmHg (95%CI: 17 to 39 mmHg, P < 0.00001). Granulocyte macrophage-colony stimulating factor failed to show a significant increase in anastomotic bursting pressure (95%CI: -20 to 21 mmHg, P = 0.97) vs controls in experimental chemotherapeutic models.

CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis.

Keywords: Anastomotic healing; Colorectal surgery; Breaking strength; Bursting pressure; Anastomotic leakage; Ischemia; Chemotherapy; Reperfusion; Bowel obstruction; Peritonitis; Radiotherapy

Core tip: Anastomotic leakage is a challenging complication after colorectal surgery. Although many pharmaceutical compounds have the potential to improve anastomotic healing, none has reached the clinical setting. This study reviewed 65 experimental studies investigating 48 different therapeutic agents for the improvement of anastomotic healing under complicated conditions due to ischemia, ischemia/reperfusion, obstructive bowel, obstructive jaundice, peritonitis, chemotherapy or radiotherapy. Of the 31 agents reported to enhance anastomotic healing, one was subjected to a meta-analysis. Hyperbaric oxygen therapy significantly improved anastomotic healing in rat models complicated by bowel ischemia. Further exploration is needed to define agents that reduce AL in high-risk patients.