K. Mahendraraj1, R. S. Chamberlain1,2,3 1Saint Barnabas Medical Center,Department Of Surgery,Livingston, NJ, USA 2New Jersey Medical School,Department Of Surgery,Newark, NJ, USA 3Saint George’s University,Department Of Surgery,Grenada, Grenada, Grenada
Introduction:
Pancreatic fistulas remain one of the most common and detrimental complications following the Whipple operation (pancreaticoduodenectomy). The prophylactic use of somatostatin analogues (SA) for the prevention of pancreatic fistulas is controversial. This meta-analysis aimed to assess the effectiveness of SA in preventing pancreatic fistulas among the conflicting data from published randomized controlled trials.
Methods:
A comprehensive search of PUBMED, Embase and both the Cochrane and NIH Clinical Trial Registries was completed using the keywords ‘somatostatin’, ‘octreotide’, ‘fistula’, and ‘randomized controlled trial (RCT)’. Citations of relevant review articles were examined. Data on patient recruitment, intervention and outcome were extracted from the included trials and analyzed. 42 full-text articles were identified in this manner, and 22 of these were excluded for lack of randomization, inadequate blinding and incomplete outcome data. Only RCTs which were completed and had an endpoint of ‘pancreatic fistula’ were included. The risk ratio (RR) was calculated with 95% confidence intervals.
Results:
20 RCTs involving 2,596 patients who underwent pancreaticoduodenectomy were identified. 1,312 patients (50.5%) were randomized to receive SA while 1,284 patients (49.5%) received either a placebo or no intervention. The incidence of pancreatic fistula was 32% lower in the SA group (RR 0.68, 95% CI 0.54-0.86;p=0.001). The proportion of these fistulas that were clinically significant is not clear. On subgroup analysis, there was no significant difference in perioperative mortality between the two groups (RR 0.80, 95% CI 0.56-1.16; p=0.24), but there was a 30% lower incidence of overall complications in the SA group (RR 0.70, 95% CI 0.60-0.82; p=0.03). Significant heterogeneity was found among the identified trials with regard to the definition of fistula, dosage of octreotide, starting time and duration of treatment.
Conclusion:
The use of SA following pancreaticoduodenectomy significantly reduces both pancreatic fistula and overall complication rates, with no effect on perioperative mortality. Available data suggests a role for routine prophylactic SA use to improve patient outcomes following major pancreatic resection. Further clarification of the effects of these drugs is required through additional large, adequately powered randomized controlled trials with low risk of bias.
