Does surgical glue prevent postoperative pancreatic fistula (leaking of fluid from the pancreas) and promote healing after surgery?

Key messages

- Surgical glue may make little to no difference to postoperative pancreatic fistula in people undergoing removal of the pancreatic tail.

- We do not know if surgical glue has an effect on postoperative pancreatic fistula in people undergoing removal of the pancreatic head.

- We also do not know if surgical glue has an effect on death rate in people undergoing either of these pancreatic surgeries.

What is a postoperative pancreatic fistula?

A postoperative pancreatic fistula is a potentially life-threatening complication that may follow major surgery for cancer or inflammation of the pancreas. The pancreas is a digestive gland situated at the back of the upper abdomen. A fistula occurs when the pancreatic stump or the reconnection between the pancreas and the nearby gut does not heal properly, creating a leak of pancreatic juice from the pancreas to the abdominal tissue. This delays recovery from surgery and often requires further treatment to ensure complete healing.

How is this prevented?

Surgical 'glue' – also called 'surgical tissue adhesive' – is a product derived from human or animal blood, and is used to close wounds and help control bleeding in various surgeries. Surgical glue has been used in recent years to prevent postoperative pancreatic fistula after pancreatic surgery. However, its effectiveness and safety in this type of surgery is still uncertain.

What did we want to find out?

We wanted to find out whether surgical glue is effective in preventing postoperative pancreatic fistula after pancreatic surgery in any care setting, compared with no glue. We looked at:

- postoperative pancreatic fistula rate;
- death rate;
- overall complication rate;
- additional operation rate;
- if there were any harmful or unwanted effects;
- participant health-related quality of life/health status;
- hospital cost;
- total length of hospital stay.

What did we do?

We searched for studies that compared surgical glue use with no glue in people undergoing pancreatic surgery. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 14 studies in total, with 1989 participants. We divided the studies into three comparison groups, as the people in these studies underwent three different types of pancreatic operation, requiring different applications of surgical glue.

Comparison 1 
We found 8 studies with 1119 participants who underwent removal of the 'tail' of the pancreas. In this operation, surgical glue is applied to the pancreatic stump. Compared with no glue, surgical glue may make little to no difference to:

- postoperative pancreatic fistula rate;
- overall complication rate.

Surgical glue may reduce the additional operation rate slightly compared to no glue. There were no harmful or unwanted effects related to surgical glue use in these studies. However, we do not know if its use has an effect on:

- death rate;
- total length of hospital stay.

These 8 studies did not report on participant health-related quality of life/health status and hospital cost.

Comparison 2
We found 5 studies with 519 participants who underwent removal of the pancreatic 'head'. In this operation, surgeons create a connection between the pancreatic stump and the small intestine, and surgical glue is applied to reinforce this connection. We do not know if surgical glue has an effect on:

- postoperative pancreatic fistula rate;
- death rate;
- additional operation rate;
- hospital cost.

Compared with no glue, surgical glue may make little to no difference to:

- overall complication rate;
- total length of hospital stay.

There were no harmful or unwanted effects related to surgical glue use in this comparison. These studies did not report on participant health-related quality of life/health status.

Comparison 3
We found two studies with 351 participants who underwent removal of the pancreatic 'head', where surgical glue is used to seal the main pancreatic duct. We do not know if surgical glue use has an effect on:

- death rate;
- overall complication rate;
- additional operation rate.

Compared with no glue, surgical glue may increase unwanted effects (diabetes mellitus) for these patients. It may make little to no difference to total length of hospital stay.

These two studies did not report on postoperative pancreatic fistula rate, hospital cost, and participant health-related quality of life/health status.

What are the limitations of the evidence?

We are not confident in the evidence because it is possible that people in the studies were aware of what treatment they were getting, and not all the studies provided information about everything that were interested in. Some studies did not clearly report how they were conducted, and there are not enough studies to be certain about the results of our outcomes.

How up to date is this evidence?

We searched for studies that had been published up to March 2023.

Authors' conclusions: 

Based on the current available evidence, fibrin sealant use may result in little to no difference in the rate of POPF in people undergoing distal pancreatectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF in people undergoing pancreaticoduodenectomy. The effect of fibrin sealant use on postoperative mortality is uncertain in people undergoing either distal pancreatectomy or pancreaticoduodenectomy.

Read the full abstract...
Background: 

Postoperative pancreatic fistula (POPF) is one of the most frequent and potentially life-threatening complications following pancreatic surgery. Fibrin sealants have been used in some centres to reduce POPF rate. However, the use of fibrin sealant during pancreatic surgery is controversial. This is an update of a Cochrane Review last published in 2020.

Objectives: 

To evaluate the benefits and harms of fibrin sealant use for the prevention of POPF (grade B or C) in people undergoing pancreatic surgery compared to no fibrin sealant use.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, two other databases, and five trials registers on 09 March 2023, together with reference checking, citation searching, and contacting study authors to identify additional studies.

Selection criteria: 

We included all randomised controlled trials (RCTs) 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: 

We used standard methodological procedures expected by Cochrane.

Main results: 

We included 14 RCTs, randomising 1989 participants, comparing fibrin sealant use versus no fibrin sealant use for different locations: stump closure reinforcement (eight trials), pancreatic anastomosis reinforcement (five trials), or main pancreatic duct occlusion (two trials). Six RCTs were carried out in single centres; two in dual centres; and six in multiple centres. One RCT was conducted in Australia; one in Austria; two in France; three in Italy; one in Japan; two in the Netherlands; two in South Korea; and two in the USA. The mean age of the participants ranged from 50.0 years to 66.5 years. All RCTs were at high risk of bias.

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

We included eight RCTs involving 1119 participants: 559 were randomised to the fibrin sealant group and 560 to the control group after distal pancreatectomy. Fibrin sealant use may result in little to no difference in the rate of POPF (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.73 to 1.21; 5 studies, 1002 participants; low-certainty evidence) and overall postoperative morbidity (RR 1.20, 95% CI 0.98 to 1.48; 4 studies, 893 participants; low-certainty evidence). After fibrin sealant use, approximately 199 people (155 to 256 people) out of 1000 developed POPF compared with 212 people out of 1000 when no fibrin sealant was used. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto odds ratio (OR) 0.39, 95% CI 0.12 to 1.29; 7 studies, 1051 participants; very low-certainty evidence) and total length of hospital stay (mean difference (MD) 0.99 days, 95% CI -1.83 to 3.82; 2 studies, 371 participants; very low-certainty evidence). Fibrin sealant use may reduce the reoperation rate slightly (RR 0.40, 95% CI 0.18 to 0.90; 3 studies, 623 participants; low-certainty evidence). Serious adverse events were reported in five studies (732 participants), and there were no serious adverse events related to fibrin sealant use (low-certainty evidence). The studies did not report quality of life or cost-effectiveness.

Application of fibrin sealants to pancreatic anastomosis reinforcement after pancreaticoduodenectomy

We included five RCTs involving 519 participants: 248 were randomised to the fibrin sealant group and 271 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on the rate of POPF (RR 1.34, 95% CI 0.72 to 2.48; 3 studies, 323 participants; very low-certainty evidence), postoperative mortality (Peto OR 0.24, 95% CI 0.05 to 1.06; 5 studies, 517 participants; very low-certainty evidence), reoperation rate (RR 0.74, 95% CI 0.33 to 1.66; 3 studies, 323 participants; very low-certainty evidence), and total hospital cost (MD -1489.00 US dollars, 95% CI -3256.08 to 278.08; 1 study, 124 participants; very low-certainty evidence). After fibrin sealant use, approximately 130 people (70 to 240 people) out of 1000 developed POPF compared with 97 people out of 1000 when no fibrin sealant was used. Fibrin sealant use may result in little to no difference both in overall postoperative morbidity (RR 1.02, 95% CI 0.87 to 1.19; 4 studies, 447 participants; low-certainty evidence) and in total length of hospital stay (MD -0.33 days, 95% CI -2.30 to 1.63; 4 studies, 447 participants; low-certainty evidence). Serious adverse events were reported in two studies (194 participants), and there were no serious adverse events related to fibrin sealant use (very low-certainty evidence). The studies did not report quality of life.

Application of fibrin sealants to pancreatic duct occlusion after pancreaticoduodenectomy

We included two RCTs involving 351 participants: 188 were randomised to the fibrin sealant group and 163 to the control group after pancreaticoduodenectomy. The evidence is very uncertain about the effect of fibrin sealant use on postoperative mortality (Peto OR 1.41, 95% CI 0.63 to 3.13; 2 studies, 351 participants; very low-certainty evidence), overall postoperative morbidity (RR 1.16, 95% CI 0.67 to 2.02; 2 studies, 351 participants; very low-certainty evidence), and reoperation rate (RR 0.85, 95% CI 0.52 to 1.41; 2 studies, 351 participants; very low-certainty evidence). Fibrin sealant use may result in little to no difference in the total length of hospital stay (median 16 to 17 days versus 17 days; 2 studies, 351 participants; low-certainty evidence). Serious adverse events were reported in one study (169 participants; low-certainty evidence): 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 POPF, quality of life, or cost-effectiveness.