Abstract
Aims
To investigate effect of cyanoacrylate-based glue on postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy.
Methods
A PRISMA-compliant systematic review and meta-analysis using random effects modelling was performed including studies investigating effect of cyanoacrylate-based glue on postoperative leak and bleeding in patients undergoing pancreatectomy and sleeve gastrectomy. Proportion meta-analysis and comparison meta-analysis were modelled to evaluate the outcomes.
Results
Analysis of 1800 patients from nine studies showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups in all pancreatic resections (OR: 1.26, p = 0.700), in pancreaticoduodenectomy with total duct occlusion (OR: 3.21, p = 0.360), in pancreaticoduodenectomy with pancreaticojejunostomy (OR: 0.42, p = 0.550), in distal pancreatectomy (OR: 1.50, p = 0.330), and in sleeve gastrectomy (OR: 0.14, p = 0.07). Moreover, there was no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups in all pancreatic resections (OR: 1.44, p = 0.460), in pancreaticoduodenectomy with total duct occlusion (OR: 0.35, p = 0.520), in pancreaticoduodenectomy with pancreaticojejunostomy (OR: 2.75, p = 0.080), in distal pancreatectomy (OR: 0.72, p = 0.670), and in sleeve gastrectomy (OR: 0.37, p = 0.14). Cyanoacrylate-based glue did not reduce the risk of grade A (OR: 1.16, p = 0.82), grade B (OR: 1.29, p = 0.460), and grade C (OR: 0.36, 3.16, p = 0.360) postoperative pancreatic fistula.
Conclusions
Level 2 evidence with moderate certainty suggests that cyanoacrylate-based glue does not reduce the risk of postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy. More studies with larger sample sizes are required to exclude type 2 error.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00423-026-03973-z.
Keywords: Pancreaticoduodenectomy, Pancreatectomy, Sleeve gastrectomy, Leak, Glue
Introduction
Despite advances in technology and improvement in operative skills, postoperative leak or bleeding from a resection line remain major cause of morbidity after pancreatic and bariatric surgery [1–4]. Clinically relevant postoperative pancreatic fistula (POPF) and postoperative bleeding can occur in approximately 15% and 16% of patients undergoing pancreatic resection, respectively [1, 2]. Moreover, staple line leak and bleeding can occur in up to 4.7% and 4% of patients undergoing sleeve gastrectomy, respectively [3, 4]. Consequently, there have been ongoing effort for developing strategies to reduce the risk of postoperative leak and bleeding after both pancreatic surgery and bariatric surgery [5–8].
Application of tissue adhesive glue on pancreatic stump, pancreatic-enteric anastomosis, or gastric staple line gained popularity as a strategy to reduce the risk of leak or bleeding. There are different types of tissue adhesive glues including fibrin-based glue (fibrinogen and thrombin), cyanoacrylate-based glue, and collagen-based glue. The best available evidence did not show any benefits in favour of using fibrin glue in pancreatic surgery [6, 9, 10]. In bariatric surgery, the available evidence suggested that although fibrin glue does not reduce the risk of staple line leak, it may reduce the risk of staple line bleeding [8]. Lack of evidence supporting effectiveness of fibrin glue in reducing the risk of resection line leak or bleeding has encouraged researchers to investigate the role of cyanoacrylate-based glue in this setting. Cyanoacrylate is an acrylic resin that joins surfaces together by rapidly polymerizing in the presence of water resulting in formation of a strong bond. It can be applied to the resection surface easily and may not be degraded by pancreatic enzymes due to its long-lasting tissue bonds.
The effects of cyanoacrylate-based glue on postoperative leak and postoperative bleeding have been investigated by several studies providing a robust rationale for conducting a systematic review. In view of this, we conducted a systematic review and meta-analysis to investigate effect of cyanoacrylate-based glue on postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy.
Methods
Methodological and reporting compliance
The study was conducted and reported in compliance with the Cochrane Handbook for Systematic Reviews (version 6.4)[11] and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement standards[12], respectively.
Registration and protocol
The study followed a pre-defined protocol which was prospectively registered in PROSPERO which is a publicly available international database of prospectively registered systematic reviews (PROSPERO registration number: CRD42024616296).
Eligibility criteria
Study design
All retrospective and prospective studies (randomised controlled trials, cohort studies, case-control studies, and case series) with minimum sample size of 10 patients were considered eligible for inclusion in this study. Systematic reviews, meta-analyses, scoping reviews, review articles, case reports, and correspondence articles were excluded.
Population
All adult patients aged 18 or over who underwent any form of pancreatectomy (pancreaticoduodenectomy with total duct occlusion, pancreaticoduodenectomy with pancreaticojejunostomy, distal pancreatectomy, or central pancreatectomy) or sleeve gastrectomy were eligible. All approaches including open, laparoscopic, laparoscopic-assisted, robotic, or robotic-assisted were considered eligible.
Intervention and comparison
Use of any form of cyanoacrylate-based glue (Glubran, Dermabond, or Omnex) was considered as intervention of interest. When comparison was possible, placebo or no glue were considered as comparisons of interest.
Outcomes
The outcomes of interest for patients undergoing pancreatic resection included: postoperative pancreatic leak, grade A, B, and C postoperative pancreatic fistula (POPF), and postoperative bleeding. The outcomes of interest for patients undergoing sleeve gastrectomy included postoperative leak from stapled line and postoperative bleeding.
Information sources and search strategy
A comprehensive search strategy consisting of proper search keywords, limits, thesaurus headings and operators was created, adopted, and applied on the following electronic sources: Scopus®, MEDLINE®, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, the International Standard Randomised Controlled Trial Number Registry, the International Clinical Trials Registry Platform, ClinicalTrials.gov and the Grey Literature Network Service (APPENDIX I). Two authors with expertise in evidence synthesis designed and applied the search strategy on 20 October 2024 with no language restrictions.
Study selection, data collection, and data items
Two authors independently screened the identified articles through titles and abstracts against the eligibility criteria and retrieved the full text of potentially eligible articles. Articles that met the eligibility criteria were selected for inclusion. If there was discrepancy in the findings of the first two authors, a third author provided an opinion on eligibility. The data items were determined at the protocol development stage by the authors with expertise in the field and after selection of eligible studies by the authors with expertise in evidence synthesis using a pilot-testing technique of randomly selected studies. Data items were collected in an electronic data collection sheet by two independent authors. These included information about the bibliometric parameters, study design, included population and their demographic parameters, body mass index (BMI), type of glue, comparison arm, operative time, and the outcomes.
Study risk of bias assessment
The risk of bias in randomised controlled trials was judged using the Cochrane risk of bias tool and the risk of bias in observational studies was evaluated using Risk Of Bias In Non- Randomized Studies- of Interventions (ROBINS-I) tool by two independent authors. If there was any discrepancy in assessment by the first two authors, a third author provided opinion.
Effect measures and synthesis methods
OpenMeta[Analyst] software was employed for proportion meta-analysis model and RevMan 5.4 software (Nordic Cochrane Centre, Copenhagen, Denmark) was employed for comparison meta-analysis model. In the proportion meta-analysis model, numerical estimates of the overall effect (pooled risk for dichotomous variables) were calculated after integrating quantitative figures from individual studies. In the comparison meta-analysis model, odds ratio (OR) was calculated as summary effect measure for dichotomous variables. Random-effects modelling was used for analyses and forest plots with 95% confidence intervals (CIs) were constructed to present the results. Individual patients were considered as unit of analysis. Statistical heterogeneity was measured as I2 using Cochran’s Q test (χ2), and heterogeneity was classified as low when I2 was 0–25%, moderate when I2 was 25–75% and high when I2 was 75–100%. Sensitivity analyses (leave-one-out analysis and separate analysis for studies with low overall risk of bias) were performed if the outcome was reported by a minimum of four studies.
Reporting bias assessment
The protocol planned to evaluate the risk of reporting bias by constructing a funnel plot if the outcomes were reported by at least ten studies; however, because the outcomes were reported by less than ten studies, reporting bias could not be evaluated.
Certainty assessment
The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used for assessment of the certainty of evidence for operative mortality [13].
Deviation from the registered protocol
The study remained compliant with the registered protocol with no deviations.
Results
Study selection and study characteristics
Search of the information sources resulted in 76 articles; 67 articles were excluded directly by screening their titles and abstracts. The full-text review of the remaining nine articles were reviewed and all were found to be eligible for inclusion. Therefore, nine studies [14–22] (one randomised controlled trial and eight observational studies) including 1800 eligible patients were included. The study PRISMA flow diagram is shown in Fig. 1 and baseline characteristics of the included studies are shown in Table 1.
Fig. 1.
Study PRISMA flow diagram
Table 1.
Baseline characteristics of the included studies
| Authors | Year | Country | Journal | Design | Procedure | Cyanoacrylate glue used | Comparison | Sample size | |
|---|---|---|---|---|---|---|---|---|---|
| Cyanoacrylate glue | Comparison | ||||||||
| Martines et al. [14] | 2022 | Italy | Open Medicine | Retrospective cohort | Laparoscopic sleeve gastrectomy | Glubran | No glue | 70 | 50 |
| Giuliani et al. [15] | 2021 | Italy | Frontiers in Surgery | Retrospective cohort | Pancreaticoduodenectomy with duct occlusion | Glubran | - | 48 | - |
| Pilone et al. [16] | 2019 | Italy | BMC Surgery | Randomised controlled trial | Laparoscopic sleeve gastrectomy | Glubran | No glue | 96 | 90 |
| Gonzalez-Heredia et al. [17] | 2018 | USA | Gastrointest Tumors | Retrospective cohort | Pancreaticoduodenectomy with duct occlusion | Not reported | No glue | 18 | 51 |
| Huttner et al. [18] | 2018 | Germany | PLoS ONE | Prospective cohort | Distal pancreatectomy | Omnex | - | 15 | - |
| Martines et al. [19] | 2017 | Italy | Giornale di chirurgia | Prospective cohort | Laparoscopic sleeve gastrectomy | Glubran | Fibrin glue | 25 | 25 |
| Tillmann et al. [20] | 2017 | Germany | World Journal of Surgery | Retrospective cohort | Pancreaticoduodenectomy with pancreatojejunostomy or Distal pancreatectomy | Dermabond | No glue | 52 | 1086 |
| Mezza et al. [21] | 2015 | Italy | American Journal of Surgery | Retrospective cohort | Pancreaticoduodenectomy with duct occlusion | Glubran | No glue | 24 | 26 |
| Barakat et al. [22] | 2012 | USA | Journal of gastrointestinal surgery | Retrospective cohort | Pancreaticoduodenectomy with pancreatojejunostomy | Dermabond | No glue | 75 | 49 |
Risk of bias in studies
Figure 2 shows the outcomes of methodological quality assessment of the included studies based on the Cochrane risk of bias tool and the ROBINS-I tool.
Fig. 2.
Results of risk of bias assessment for: (a) Randomised controlled trial; (b) Observational studies
Cyanoacrylate-based glue and postoperative leak
All pancreatic resections
Proportion meta-analysis of 232 patients from six studies showed that the risk of pancreatic leak after use of cyanoacrylate-based glue was 41.3% (95% CI 16.1–66.5) (Fig. 3). The statistical heterogeneity was high (I2 = 96%) and the GRADE certainty was moderate. The comparison meta-analysis of 1381 patients from four studies showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups (OR: 1.26, 95% CI 0.40, 3.99, p = 0.700) (Fig. 4). The statistical heterogeneity was high (I2 = 81%) and the GRADE certainty was moderate.
Fig. 3.
Forest plots for the outcomes in proportion meta-analysis model: (a) Postoperative leak in pancreatic resection; (b) Grade A postoperative pancreatic fistula; (c) Grade B postoperative pancreatic fistula; (d) Grade C postoperative pancreatic fistula; (e) Postoperative leak in sleeve gastrectomy; (f) Postoperative bleeding in pancreatic resection; (g) Postoperative bleeding in sleeve gastrectomy
Fig. 4.
Forest plots for the outcomes in comparison meta-analysis model: (a) Postoperative leak in pancreatic resection; (b) Grade A postoperative pancreatic fistula; (c) Grade B postoperative pancreatic fistula; (d) Grade C postoperative pancreatic fistula; (e) Postoperative leak in sleeve gastrectomy; (f) Postoperative bleeding in pancreatic resection; (g) Postoperative bleeding in sleeve gastrectomy
Pancreaticoduodenectomy with total duct occlusion
Proportion meta-analysis of 90 patients from three studies showed that the risk of pancreatic leak after use of cyanoacrylate-based glue in pancreaticoduodenectomy with total duct occlusion was 46.8% (95% CI 21.4–72.2) (Fig. 3). The statistical heterogeneity was high (I2 = 84%) and the GRADE certainty was low. The comparison meta-analysis of 119 patients from two studies showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups (OR: 3.21, 95% CI 0.26, 39.73, p = 0.360) (Fig. 4). The statistical heterogeneity was high (I2 = 86%) and the GRADE certainty was low.
Pancreaticoduodenectomy with pancreaticojejunostomy
Proportion meta-analysis of 110 patients from two studies showed that the risk of pancreatic leak after use of cyanoacrylate-based glue in pancreaticoduodenectomy with pancreaticojejunostomy was 14.8% (95% CI 0.0–41.1.0.1) (Fig. 3). The statistical heterogeneity was high (I2 = 89%) and the GRADE certainty was low. The comparison meta-analysis of 901 patients from two studies showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups (OR: 0.42, 95% CI 0.02, 7.22, p = 0.550) (Fig. 4). The statistical heterogeneity was high (I2 = 90%) and the GRADE certainty was low.
Distal pancreatectomy
Proportion meta-analysis of 40 patients from two studies showed that the risk of pancreatic leak after use of cyanoacrylate-based glue in distal pancreatectomy was 60.1% (95% CI 35.3–84.9) (Fig. 3). The statistical heterogeneity was moderate (I2 = 64%) and the GRADE certainty was moderate. The comparison meta-analysis of 361 patients from one study showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups (OR: 1.50, 95% CI 0.66, 3.39, p = 0.330) (Fig. 4). The GRADE certainty was moderate.
Sleeve gastrectomy
Proportion meta-analysis of 191 patients from three studies showed that the risk of postoperative leak after use of cyanoacrylate-based glue in sleeve gastrectomy was 0.6% (95% CI 0.0–1.8.0.8) (Fig. 3). The statistical heterogeneity was low (I2 = 0%) and the GRADE certainty was high. The comparison meta-analysis of 306 patients from two studies showed no difference in the risk of postoperative leak between the cyanoacrylate-based glue and no glue groups (OR: 0.14, 95% CI 0.02, 1.14, p = 0.07) (Fig. 4). The statistical heterogeneity was low (I2 = 0%) and the GRADE certainty was high.
Cyanoacrylate-based glue and grade A, B, and C POPF
All pancreatic resections
Proportion meta-analysis of 214 patients from five studies showed that the risk of grade A, grade B, and grade C POPF after use of cyanoacrylate-based glue was 14.1% (95% CI 4.3–23.9), 15.6.3% (95% CI 4.7–26.6), and 3% (95% CI 0.0–6.0), respectively (Fig. 3). The comparison meta-analysis of 1312 patients from three studies showed no difference in the risk of grade A (OR: 1.16, 95% CI 0.32, 4.25, p = 0.82), grade B (OR: 1.29, 95% CI 0.65, 2.57, p = 0.460), and grade C (OR: 0.36, 95% CI 0.04, 3.16, p = 0.360) POPF between the cyanoacrylate-based glue and no glue groups (Fig. 4).
Pancreaticoduodenectomy with total duct occlusion
Proportion meta-analysis of 72 patients from two studies showed that the risk of grade A, grade B, and grade C POPF after use of cyanoacrylate-based glue in pancreaticoduodenectomy with total duct occlusion was 20.8% (95% CI 11.5–30.2), 20.4% (95% CI 0.0–53.0), and 3.7% (95% CI 0.0–7.9.0.9), respectively (Fig. 3). The comparison meta-analysis of 50 patients from one study showed no difference in the risk of grade A (OR: 6.58, 95% CI 0.71, 61.08, p = 0.100), grade B (OR: 0.24, 95% CI 0.02, 2.31, p = 0.220), and grade C (OR: 0.20, 95% CI 0.01, 4.38, p = 0.310) POPF between the cyanoacrylate-based glue and no glue groups (Fig. 4).
Pancreaticoduodenectomy with pancreaticojejunostomy
Proportion meta-analysis of 102 patients from two studies showed that the risk of grade A, grade B, and grade C POPF after use of cyanoacrylate-based glue in pancreaticoduodenectomy with pancreaticojejunostomy was 2.4% (95% CI 0.0–7.0), 2.4% (95% CI 0.0–7.0), and 6.1% (95% CI 0.0–19.6.0.6), respectively (Fig. 3). The comparison meta-analysis of 901 patients from two studies showed no difference in the risk of grade A (OR: 0.43, 95% CI 0.04, 4.25, p = 0.470), grade B (OR: 1.12, 95% CI 0.29, 4.24, p = 0.870), and grade C (OR: 0.39, 95% CI 0.00, 31.68, p = 0.670) POPF between the cyanoacrylate-based glue and no glue groups (Fig. 4).
Distal pancreatectomy
Proportion meta-analysis of 40 patients from two studies showed that the risk of grade A, grade B, and grade C POPF after use of cyanoacrylate-based glue in distal pancreatectomy was 23.9% (95% CI 0.0–51.0), 28.5% (95% CI 12.8–44.1), and 4.6% (95% CI 0.0–14.0), respectively (Fig. 3). The comparison meta-analysis of 361 patients from one study showed no difference in the risk of grade A (OR: 1.63, 95% CI 0.46, 5.79, p = 0.450), grade B (OR: 1.74, 95% CI 0.74, 4.09, p = 0.200), and grade C (OR: 0.30, 95% CI 0.02, 5.15, p = 0.410) POPF between the cyanoacrylate-based glue and no glue groups (Fig. 4).
Cyanoacrylate-based glue and postoperative bleeding
All pancreatic resections
Proportion meta-analysis of 214 patients from five studies showed that the risk of postoperative bleeding after use of cyanoacrylate-based glue was 5.8% (95% CI 1.2–10.5) (Fig. 3). The statistical heterogeneity was moderate (I2 = 60%) and the GRADE certainty was moderate. The comparison meta-analysis of 1312 patients from three studies showed no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups (OR: 1.44, 95% CI 0.55, 3.79, p = 0.460) (Fig. 4). The statistical heterogeneity was low (I2 = 14%) and the GRADE certainty was high.
Pancreaticoduodenectomy with total duct occlusion
Proportion meta-analysis of 72 patients from two studies showed that the risk of postoperative bleeding after use of cyanoacrylate-based glue in pancreaticoduodenectomy with total duct occlusion was 10.7% (95% CI 0.0–29.1.0.1) (Fig. 3). The statistical heterogeneity was high (I2 = 88%) and the GRADE certainty was moderate. The comparison meta-analysis of 50 patients from one study showed no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups (OR: 0.35, 95% CI 0.01, 8.93, p = 0.520) (Fig. 4). The GRADE certainty was low.
Pancreaticoduodenectomy with pancreaticojejunostomy
Proportion meta-analysis of 102 patients from two studies showed that the risk of postoperative bleeding after use of cyanoacrylate-based glue in pancreaticoduodenectomy with pancreaticojejunostomy was 4.9% (95% CI 0.0–12.3.0.3) (Fig. 3). The statistical heterogeneity was moderate (I2 = 44%) and the GRADE certainty was moderate. The comparison meta-analysis of 901 patients from two studies showed no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups (OR: 2.75, 95% CI 0.90, 8.40, p = 0.080) (Fig. 4). The statistical heterogeneity was low (I2 = 0%) and the GRADE certainty was moderate.
Distal pancreatectomy
Proportion meta-analysis of 40 patients from two studies showed that the risk of postoperative bleeding after use of cyanoacrylate-based glue in distal pancreatectomy was 4.6% (95% CI 0.0–14.0) (Fig. 3). The statistical heterogeneity was moderate (I2 = 35%) and the GRADE certainty was moderate. The comparison meta-analysis of 361 patients from one study showed no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups (OR: 0.72, 95% CI 0.16, 3.20, p = 0.670) (Fig. 4). The GRADE certainty was moderate.
Sleeve gastrectomy
Proportion meta-analysis of 191 patients from three studies showed that the risk of postoperative bleeding after use of cyanoacrylate-based glue in sleeve gastrectomy was 1.8% (95% CI 0.0–3.6.0.6) (Fig. 3). The statistical heterogeneity was low (I2 = 0%) and the GRADE certainty was high. The comparison meta-analysis of 306 patients from two studies showed no difference in the risk of postoperative bleeding between the cyanoacrylate-based glue and no glue groups (OR: 0.37, 95% CI 0.10, 1.40, p = 0.14) (Fig. 4). The statistical heterogeneity was low (I2 = 0%) and the GRADE certainty was high.
Sensitivity analyses
Leave-one-out analysis and separate analysis for studies with low overall risk of bias did not affect direction of effect size.
Discussion
We conducted a systematic review and meta-analysis with meta-regression to investigate effect of cyanoacrylate-based glue on postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy. Analysis of 1800 patients from nine studies showed no difference in the risk of postoperative leak and postoperative bleeding between the cyanoacrylate-based glue and no glue groups in all pancreatic resections, pancreaticoduodenectomy with total duct occlusion, pancreaticoduodenectomy with pancreaticojejunostomy, distal pancreatectomy, and sleeve gastrectomy. Moreover, cyanoacrylate-based glue did not reduce the risk of grade A, B, and C POPF in all pancreatic resections, pancreaticoduodenectomy with total duct occlusion, pancreaticoduodenectomy with pancreaticojejunostomy, and distal pancreatectomy. The overall GRADE certainty of moderate.
This study is the first meta-analysis evaluating the effect of cyanoacrylate-based glue on postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy. Consequently, the results cannot be compared with another similar systematic review; nevertheless, the results of current study can be compared with studies that evaluated use of fibrin glue in this setting. Orci et al.6 conducted a systematic review of 897 patients from seven studies and concluded that fibrin glue does not affect the risk of POPF and postoperative bleeding in patients undergoing pancreatic resection. In another study, Lai et al.10 analysed 1,989 patients from 14 randomised controlled trials which could not show any benefits associated with use of fibrin glue in patients undergoing pancreatic resection [10]. Chen et al.8 analysed 2136 patients from nine randomised controlled trials which concluded that although fibrin glue does not reduce the risk of staple line leak, it may reduce the risk of staple line bleeding in bariatric surgery [8].
The results of the current study suggest that the theoretical advantages of cyanoacrylate-based glue may not translate into clinical benefits. As mentioned previously, cyanoacrylate is an acrylic resin that joins surfaces together by rapidly polymerizing in the presence of water resulting in formation of a strong bond and is thought not to be degraded by pancreatic enzymes; nevertheless, based on the results of current study, we can argue it may not reduce the risk of resection line leak or bleeding. Considering the quality of the included studies and heterogeneity among the included studies, randomised controlled trials with larger sample size would be required for definite conclusions; nevertheless, until higher level of evidence is available, the effectiveness of cyanoacrylate-based glue remains unproven.
The current study has some limitations. The available evidence is mainly derived from observational studies and may be subject to selection bias and confounding bias. The included studies had relatively small sample sizes and the number of included studies in each subgroup was small increasing the likelihood of type 2 error in this study. The publication bias could not be assessed formally due to not having more than 10 eligible studies. The statistical between-study heterogeneity was moderate to high for most of the outcomes. We explored and addressed the observed statistical heterogeneity via different strategies. Firstly, we used random-effects model for all of the analyses. Secondly, we did leave-one-out analysis for the outcomes reported by at least 4 studies. Thirdly, we conducted a conspicuous number of subgroup analyses based on the procedures and definition of outcomes which reduced the heterogeneity significantly to less than 50% in most of the outcomes. Moreover, while we explored the heterogeneity, we downgraded the certainty of the evidence accordingly to take into account the observed heterogeneity that was not reduced with the above strategies.
Conclusions
Level 2 evidence with moderate certainty suggests that cyanoacrylate-based glue does not reduce the risk of postoperative leak and bleeding after pancreatectomy and sleeve gastrectomy. More studies with larger sample sizes are required to exclude type 2 error.
Supplementary Information
Below is the link to the electronic supplementary material.
Author contributions
Conception and design: AK, Shahab HData collection: AS, ED, NM, Shahab HAnalysis and interpretation: Shahab H, Shahin HWriting the article: Shahab H, AS, ED, NM, ST, RT, Shahin H, AKCritical revision for important intellectual content: Shahab H, AS, ED, NM, ST, RT, Shahin H, NM, MM, GS, BA, AKFinal approval of the article: Shahab H, AS, ED, NM, ST, RT, Shahin H, NM, MM, GS, BA, AK.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Data availability
The data and materials related to this study will be available upon reasonable request from the corresponding author.
Declarations
Human and animal rights
This study is a systematic review with meta-analysis of outcomes which does not include research directly involving human or animal participation.
Competing interests
The authors declare no competing interests.
PROSPERO registration number
CRD42024616296.
Footnotes
Shahab Hajibandeh, Arshad Siddiqui, and Elorm Daketsey, joint first authors.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data and materials related to this study will be available upon reasonable request from the corresponding author.