Supplemental Information

Supplemental Table 1

Search strategy. For Medline searches, surgical terms were combined with terms for NSAID use using the “AND” function. A modified search strategy was used for Embase (not shown).

Database / Terms
Medline – surgical terms / 1.  Anastomosis, Surgical*
2.  Anastomotic Leak *
3.  Anastomosis, Surgical/adverse effects
4.  Anastomosis, Surgical/methods
5.  Colorectal Neoplasms/surgery*
6.  Colon/surgery*
7.  Colectomy/adverse effects
Medline – terms for NSAIDs / 1.  Anti-Inflammatory Agents, Non-Steroidal/adverse effects*
2.  Cyclooxygenase 2 Inhibitors/adverse effects
3.  Diclofenac/ae
4.  Ketorolac/ae
Pubmed / 1.  (Non-Steroidal) and (anastomo*)
2.  (Cyclooxygenase) and (anastomo*)
3.  (Diclofenac) and (anastomo*)
4.  (Ibuprofen) and (anastomo*)
5.  (Ketorolac) and (anastomo*)
Cochrane Library/ Clinicaltrails.gov / 1.  (Non-Steroidal) and (anastomo*)
2.  (Cyclooxygenase) and (anastomo*)
3.  (Diclofenac) and (anastomo*)


Supplemental Table 2: Risk of bias for human studies

Selection / Comparability / Outcome
Representativeness of exposed cohort / Selection of non-exposed cohort / Ascertainment of exposure / Demonstration that outcome was not KNOWN at start of study / Comparability of groups on the basis of analysis / Assessment of outcome / Was follow up long enough for outcomes to occur? / Adequacy of follow up of cohorts / Total
Study / Was NSAID use protocolised/RCT* or selective (0)? / Same hospital and/or surgeon? / Surgical records/ hospital database? / Retrospective*, prospective assessment/RCT** / Study controls for surgical parameters (i.e. protocolised surgery) / Blinded assessment? / Details / Outcome assessment at least 30 days / (<10% loss to follow-up)
Chen 2005 / 1 / 1 / 1 / 1 / 1 / 0 / Unclear / 1 / 1 / 7
Chen 2009 / 1 / 1 / 1 / 1 / 1 / 0 / Unclear / 1 / 1 / 7
Gorissen / 0 / 1 / 1 / 1 / 1 / 0 / 1 / 1 / 6
Holte / 1 / 1 / 1 / 1 / 1 / 0 / Unclear / 1 / 1 / 7
Klein / 0 / 1 / 1 / 1 / 1 / 1 / Coding by blinded assessment / 1 / 1 / 7
Schlachta / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 8
Sim / 1 / 1 / 1 / 1 / 1 / 0 / Unclear / 1 / 1 / 7
Wattchow / 1 / 1 / 1 / 1 / 1 / 0 / Unclear / 1 / 1 / 7


Supplemental Table 3: Outcome assessment in experimental studies

Study / Day of planned death / Anastomotic integrity assured prior to closure? / Definition of anastomotic leak / Determination of bursting pressure / Determination of breaking strength
Benjamin / 7 / No / "Clinical anastomotic leak" / Inflated under saline / NA
Cahill / 3, 7 / Yes / Unclear / Inflated under Hartmann's solution / Breaking strength, Tensiometer
de Hingh / 3, 5 / No / Unclear / Saline filling / Breaking strength, Tensiometer
de Sousa / 3, 7, 14 / No / Leakage of enteric content / Inflated under water / NA
Esen / 3, 7 / No / Unclear / Saline filling / NA
Inan / 3, 7 / No / Unclear / Inflated under water / NA
Klein 2011 / 3 / No / Unclear / NA / Breaking strength, Material testing machine
Klein 2012 / 7 / No / Unclear / NA / Breaking strength, Material testing machine
Mastboom / 3, 7 / No / Macroscopic leak, Anastomotic abscess or Generalised peritonitis / NA / NA
Neuss / 3, 7 / No / Unclear / Saline filling / NA
van der Vijver / 3 / No / Macroscopic dehiscence, Fecal peritonitis, Puncture in anastomotic line / Saline filling / Breaking strength, Tensiometer
van der Vijver 2013 / 3, 7 / No / Macroscopic dehiscence, Fecal peritonitis, Puncture in anastomotic line with or without abscess / Saline filling / Breaking strength, Tensiometer

NA = not attempted