Surgical tissue adhesives for the preventing pancreatic fistula following pancreatic surgery

Review question

Is surgical tissue adhesive able to reduce postoperative pancreatic fistula after pancreatic surgery?

Background

Postoperative pancreatic fistula is a complication that may follow major surgery for cancer or inflammation of the pancreas, a digestive gland situated at the back of the upper abdomen. The surgery involves disconnecting the pancreas from the nearby gut, and then reconnecting this to allow pancreatic juice containing digestive enzymes to enter the digestive system after surgical removal of the head of the pancreas. The pancreatic stump is often left to heal itself after surgical removal of the tail of the pancreas. A fistula occurs when the reconnection or stump does not heal properly, creating a leak of pancreatic juice from the pancreas to the abdominal tissues. This delays recovery from surgery and often requires further treatment to ensure complete healing. The role of fibrin sealants (surgical tissue adhesives) to reduce postoperative pancreatic fistula after pancreatic surgery is controversial.

Study characteristics

We searched for all relevant, well-conducted studies up to April 2018. We included eleven studies which were divided into three comparisons. First, seven of the eleven studies randomized 860 participants undergoing surgical removal of the tail of the pancreas to either fibrin sealant use (428 participants) or no fibrin sealant use (432 participants) for pancreatic stump closure reinforcement. Second, three studies randomized 251 participants undergoing the 'Whipple' operation (surgical removal of the head of the pancreas) to fibrin sealant use (115 participants) or no fibrin sealant use (136 participants) for pancreatic stump reconstruction reinforcement. Third, two studies randomized 351 participants undergoing the 'Whipple' operation to fibrin sealant use (188 participants) and no fibrin sealant use (163 participants) for pancreatic duct blockage.

Key results

Application of fibrin sealants to pancreatic stump closure reinforcement after surgical removal of the tail of the pancreas

Fibrin sealants may have little to no difference in postoperative pancreatic fistula or postoperative death when fibrin sealants are used on stump closure reinforcement after surgical removal of the tail of the pancreas.

Application of fibrin sealants to pancreatic anastomosis reinforcement after 'Whipple' operation

We are uncertain whether fibrin sealants improve postoperative pancreatic fistula when used for pancreatic anastomosis reinforcement after the 'Whipple' operation. Fibrin sealants may have little to no difference on postoperative death.

Application of fibrin sealants to pancreatic duct occlusion after 'Whipple' operation

Postoperative pancreatic fistula was not reported in any of the studies. Fibrin sealants may have little to no difference in postoperative death when applied to a pancreatic duct occlusion after 'Whipple' operation.

Fibrin sealants may have little or no benefit on postoperative pancreatic fistula in people undergoing surgical removal of the tail of the pancreas. We cannot tell from our results whether fibrin sealants have an important effect on postoperative pancreatic fistula after the 'Whipple' operation because the sample size was small and the results were imprecise.

Quality of the evidence

Most of the included studies had some shortcomings in terms of how they were conducted or reported. Overall, the quality of the evidence varied from very low to moderate.

Authors' conclusions: 

Based on the current available evidence, fibrin sealants may have little or no effect on postoperative pancreatic fistula in people undergoing distal pancreatectomy. The effects of fibrin sealants on the prevention of postoperative pancreatic fistula are uncertain in people undergoing pancreaticoduodenectomy.

Read the full abstract...
Background: 

Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2016.

Objectives: 

To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery.

Search strategy: 

We searched trial registers and the following biomedical databases: the Cochrane Library (2018, Issue 4), MEDLINE (1946 to 12 April 2018), Embase (1980 to 12 April 2018), Science Citation Index Expanded (1900 to 12 April 2018), and Chinese Biomedical Literature Database (CBM) (1978 to 12 April 2018).

Selection criteria: 

We included all randomized controlled trials that compared fibrin sealant (fibrin glue or fibrin sealant patch) versus control (no fibrin sealant or placebo) in people undergoing pancreatic surgery.

Data collection and analysis: 

Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio (OR) for very rare outcomes), and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs).

Main results: 

We included 11 studies involving 1462 participants in the review.

Application of fibrin sealants to pancreatic stump closure reinforcement after distal pancreatectomy

We included seven studies involving 860 participants: 428 were randomized to the fibrin sealant group and 432 to the control group after distal pancreatectomy. Fibrin sealants may lead to little or no difference in postoperative pancreatic fistula (fibrin sealant 19.3%; control 20.1%; RR 0.96, 95% CI 0.68 to 1.35; 755 participants; four studies; low-quality evidence). Fibrin sealants may also lead to little or no difference in postoperative mortality (0.3% versus 0.5%; Peto OR 0.52, 95% CI 0.05 to 5.03; 804 participants; six studies; low-quality evidence), or overall postoperative morbidity (28.5% versus 23.2%; RR 1.23, 95% CI 0.97 to 1.58; 646 participants; three studies; low-quality evidence). We are uncertain whether fibrin sealants reduce reoperation rate (2.0% versus 3.8%; RR 0.51, 95% CI 0.15 to 1.71; 376 participants; two studies; very low-quality evidence). There is probably little or no difference in length of hospital stay between the groups (12.1 days versus 11.4 days; MD 0.32 days, 95% CI -1.06 to 1.70; 755 participants; four studies; moderate-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.

Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy

We included three studies involving 251 participants: 115 were randomized to the fibrin sealant group and 136 to the control group after pancreaticoduodenectomy. We are uncertain whether fibrin sealants reduce postoperative pancreatic fistula (1.6% versus 6.2%; RR 0.25, 95% CI 0.01 to 5.06; 57 participants; one study; very low-quality evidence). Fibrin sealants may lead to little or no difference in postoperative mortality (0.1% versus 0.7%; Peto OR 0.15, 95% CI 0.00 to 7.76; 251 participants; three studies; low-quality evidence) or length of hospital stay (12.8 days versus 14.8 days; MD -1.58 days, 95% CI -3.96 to 0.81; 181 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (33.7% versus 34.7%; RR 0.97, 95% CI 0.65 to 1.45; 181 participants; two studies; very low-quality evidence), or reoperation rate (7.6% versus 9.2%; RR 0.83, 95% CI 0.33 to 2.11; 181 participants; two studies, very low-quality evidence). The studies did not report serious adverse events, quality of life, or cost effectiveness.

Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy

We included two studies involving 351 participants: 188 were randomized to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. Fibrin sealants may lead to little or no difference in postoperative mortality (8.4% versus 6.1%; Peto OR 1.41, 95% CI 0.63 to 3.13; 351 participants; two studies; low-quality evidence) or length of hospital stay (17.0 days versus 16.5 days; MD 0.58 days, 95% CI -5.74 to 6.89; 351 participants; two studies; low-quality evidence). We are uncertain whether fibrin sealants reduce overall postoperative morbidity (32.0% versus 27.6%; RR 1.16, 95% CI 0.67 to 2.02; 351 participants; two studies; very low-quality evidence), or reoperation rate (13.6% versus 16.0%; RR 0.85, 95% CI 0.52 to 1.41; 351 participants; two studies; very low-quality evidence). Serious adverse events were reported in one study: more participants developed diabetes mellitus when fibrin sealants were applied to pancreatic duct occlusion, both at three months' follow-up (33.7% fibrin sealant group versus 10.8% control group; 29 participants versus 9 participants) and 12 months' follow-up (33.7% fibrin sealant group versus 14.5% control group; 29 participants versus 12 participants). The studies did not report postoperative pancreatic fistula, quality of life, or cost effectiveness.

Share/Save