The Role of Prophylactic Octreotide Following Pancreaticoduodenectomy to Prevent Postoperative Pancreatic Fistula: A Meta-Analysis of the Randomized Controlled Trials

Pankaj Kumar Garg; Jyoti Sharma; Ashish Jakhetiya; Nilokali Chishi

doi:10.1055/s-0038-1675359

The Surgery Journal, Table of Contents

CC BY 4.0 · Surg J (N Y) 2018; 04(04): e182-e187
DOI: 10.1055/s-0038-1675359

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Prophylactic Octreotide Following Pancreaticoduodenectomy to Prevent Postoperative Pancreatic Fistula: A Meta-Analysis of the Randomized Controlled Trials

Pankaj Kumar Garg

¹Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, New Delhi, Delhi, India

,

Jyoti Sharma

²Department of Surgical Oncology, Sawai Man Singh Medical College and Hospital, Jaipur, Rajasthan, India

,

Ashish Jakhetiya

³Department of Cancer Surgery, Vardhaman Mahaveer Medical College and Safdarjung Hospital, New Delhi, Delhi, India

,

Nilokali Chishi

¹Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, New Delhi, Delhi, India

› Author Affiliations

Abstract

Introduction A postoperative pancreatic fistula (POPF) is a major cause of morbidity and mortality following pancreaticoduodenectomy (PD). A pharmacologic approach using perioperative octreotide, a long-acting somatostatin analog having an inhibitory action on pancreatic exocrine secretion, was proposed to reduce the incidence of the POPF. Despite contradictory results in various randomized controlled trials (RCTs), the prophylactic octreotide has been widely used in the last two decades to reduce the POPF. The present meta-analysis aims to assess the effectiveness of the prophylactic octreotide in preventing the POPF following PD.

Methods A literature search was performed in the PubMed for the RCTs that compared the prophylactic octreotide with the placebo following PD published prior to October 2016. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Those RCTs which had compared the prophylactic Octreotide with placebo to reduce the POPF following PD were considered eligible for the meta-analysis. The low quality (Jadad score of two or less) RCTs or those including mixed pancreatic resections without reporting specific pancreaticoduodenectomy outcomes were excluded. The effect size for the dichotomous and the continuous data was displayed as the odds ratio (OR) and the weighted mean difference (WMD), respectively, with their corresponding 95% confidence intervals (CI). A fixed effect or random effects model was used to pool the data according to the result of a statistical heterogeneity test. The heterogeneity between the studies was evaluated using the Cochran Q statistic and the I ² test, with p < 0.05 indicating significant heterogeneity.

Results There were eight RCTs available for the analysis. A total of 959 patients were included in the meta-analysis–492 received the prophylactic octreotide and 467 patients received the placebo. The prophylactic octreotide was not found to significantly decrease the total number of the POPF (OR, 1.03'; 95% CI: 0.73–1.45; p-value 0.85) or the clinically significant POPF (OR, 0.76; 95% CI: 0.35–1.65; p-value 0.49) compared with the placebo. There was also no difference in the duration of hospital stay (WMD, 1.19; 95% CI:1.84–4.23; p-value 0.44) or the postoperative mortality (OR, 2.04; 95% CI: 0.87–4.78; p-value 0.10) between the two groups. The prophylactic octreotide was also not found to significantly delay the gastric emptying (OR, 0.76; 95% CI: 0.41–1.40; p-value 0.38).

Conclusion The present meta-analysis does not support the role of the prophylactic octreotide to prevent the POPF following PD.

Keywords

pancreatic cancer - pancreaticoduodenectomy - pancreatic fistula - octreotide - meta-analysis

Full Text

References

References
1 Reames BN, Ghaferi AA, Birkmeyer JD, Dimik JB. Hospital Volume and Operative Mortality in the Modern Era. Ann Surg 2014; 260 (02) 244-251
2 Bassi C, Dervenis C, Butturini G. , et al; International Study Group on Pancreatic Fistula Definition. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138 (01) 8-13
3 Schoellhammer HF, Fong Y, Gagandeep S. Techniques for prevention of pancreatic leak after pancreatectomy. Hepatobiliary Surg Nutr 2014; 3 (05) 276-287
4 Yeo CJ, Cameron JL, Lillemoe KD. , et al. Does prophylactic octreotide decrease the rates of pancreatic fistula and other complications after pancreaticoduodenectomy? Results of a prospective randomized placebo-controlled trial. Ann Surg 2000; 232 (03) 419-429
5 Montorsi M, Zago M, Mosca F. , et al. Efficacy of octreotide in the prevention of pancreatic fistula after elective pancreatic resections: a prospective, controlled, randomized clinical trial. Surgery 1995; 117 (01) 26-31
6 Kurumboor P, Palaniswami KN, Pramil K. , et al. Octreotide does not prevent pancreatic fistula following pancreatoduodenectomy in patients with soft pancreas and non-dilated duct: a prospective randomized controlled trial. J Gastrointest Surg 2015; 19 (11) 2038-2044
7 Suc B, Msika S, Piccinini M. , et al; French Associations for Surgical Research. Octreotide in the prevention of intra-abdominal complications following elective pancreatic resection: a prospective, multicenter randomized controlled trial. Arch Surg 2004; 139 (03) 288-294 , discussion 295
8 Kollmar O, Moussavian MR, Richter S, de Roi P, Maurer CA, Schilling MK. Prophylactic octreotide and delayed gastric emptying after pancreaticoduodenectomy: results of a prospective randomized double-blinded placebo-controlled trial. Eur J Surg Oncol 2008; 34 (08) 868-875
9 Hesse UJ, DeDecker C, Houtmeyers P. , et al. Prospectively randomized trial using perioperative low-dose octreotide to prevent organ-related and general complications after pancreatic surgery and pancreatico-jejunostomy. World J Surg 2005; 29 (10) 1325-1328
10 Lowy AM, Lee JE, Pisters PW. , et al. Prospective, randomized trial of octreotide to prevent pancreatic fistula after pancreaticoduodenectomy for malignant disease. Ann Surg 1997; 226 (05) 632-641
11 Fernández-Cruz L, Jiménez Chavarría E, Taurà P, Closa D, Boado M-AL, Ferrer J. Prospective randomized trial of the effect of octreotide on pancreatic juice output after pancreaticoduodenectomy in relation to histological diagnosis, duct size and leakage. HPB 2013; 15 (05) 392-399
12 Seetharam P, Rodrigues GS. Postoperative pancreatic fistula: a surgeon's nightmare! An insight with a detailed literature review. JOP 2015; 16 (02) 115-124
13 Yeh TS, Jan YY, Jeng LB. , et al. Pancreaticojejunal anastomotic leak after pancreaticoduodenectomy--multivariate analysis of perioperative risk factors. J Surg Res 1997; 67 (02) 119-125
14 Sato N, Yamaguchi K, Chijiiwa K, Tanaka M. Risk analysis of pancreatic fistula after pancreatic head resection. Arch Surg 1998; 133 (10) 1094-1098
15 Allen PJ, Gönen M, Brennan MF. , et al. Pasireotide for postoperative pancreatic fistula. N Engl J Med 2014; 370 (21) 2014-2022
16 Dominguez-Rosado I, Fields RC, Woolsey CA. , et al. Prospective evaluation of pasireotide in patients undergoing pancreaticoduodenectomy: the Washington University experience. J Am Coll Surg 2018; 226 (02) 147-154.e1
17 McMillan MT, Christein JD, Callery MP. , et al. Prophylactic octreotide for pancreatoduodenectomy: more harm than good?. HPB 2014; 16 (10) 954-962