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Letter to the Editor
Complications
 Comments on “Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”
Nabil Mohammad Azmi1orcid, Mohd Firdaus Mohd Hayati2orcid, Zairul Azwan Mohd Azwan1orcid
Annals of Coloproctology 2025;41(6):596-597.
DOI: https://doi.org/10.3393/ac.2025.01137.0162
Published online: December 29, 2025

1Department of Surgery, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

2Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia

Correspondence to: Nabil Mohammad Azmi, MBBS, MRCS, MSurg Department of Surgery, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Kuala Lumpur 56000, Malaysia Email: nabil@ukm.edu.my
• Received: September 19, 2025   • Accepted: October 7, 2025

© 2025 The Korean Society of Coloproctology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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See letter "In reply to: Comments on "Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”" in Volume 41 on page 598.
See the article "Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study" on page 293.
Dear Editor,
We read with great interest the recent multicenter study by Rega et al. [1], entitled “Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study.” We commend the authors for conducting a well-designed, prospective, multi-institutional trial addressing the persistent and devastating complication of anastomotic leak (AL). The reported AL rate of 1.85% in a cohort of 380 patients is impressive and, if validated, would represent a significant advancement in reducing one of the most feared complications in colorectal surgery. The application of Glubran 2 (GEM Srl) as a prophylactic sealant is a conceptually appealing strategy, leveraging its adhesive, hemostatic, and bacteriostatic properties during the critical postoperative healing phase.
Although the study’s results are promising, we wish to raise several methodological and interpretative points to contextualize these findings and propose directions for future research.
First, the study’s primary conclusion hinges on a statistically significant reduction in AL rate from a historical baseline of 6.18% to the observed 1.85% (P<0.01). The authors appropriately reference the large US database study by Hammond et al. [2] for this benchmark. However, using a decade-old, international benchmark for a contemporary, exclusively Italian cohort introduces potential historical bias. Surgical techniques, perioperative care, particularly the widespread adoption of enhanced recovery after surgery protocols, and patient management have evolved considerably since 2010. Furthermore, the 6.18% figure represents a broad average for colorectal anastomoses, encompassing higher-risk rectal cases. A more robust comparison would employ a historical control group drawn from the participating Italian centers themselves, specifically focusing on ileocolic anastomoses within a similar timeframe. This approach would better reflect institution-specific practices and temporal trends. The authors correctly note that recent European studies report AL rates for ileocolic anastomoses ranging from 3.2% to 12% [3–5]; however, selecting a single reference value of 6.18% for power calculation, rather than a range, constitutes a limitation.
Second, the observational, single-arm design represents the study’s most significant limitation. Without a control group undergoing the same surgery without Glubran 2 application, attributing the low AL rate solely to the intervention remains challenging. The authors have, in fact, provided extensive data on their cohort’s risk factors (e.g., American Society of Anesthesiologists [ASA] physical status III/IV, 55.5%). A propensity score–matched analysis using their own institutional historical data could have strengthened causal inference. The finding that known risk factors such as diabetes, smoking, and vascular disease were not associated with AL in this cohort is intriguing and potentially suggestive of a protective effect. However, in an uncontrolled study, such an observation is vulnerable to confounding. Therefore, the conclusion that Glubran 2 “mitigates the risk of AL irrespective of these preoperative factors” is provocative but requires validation in a randomized setting.
Third, the study included a mix of open (40.5%), laparoscopic (52.1%), and robotic (7.1%) approaches. The application of a nebulized sealant may vary in efficacy and technical complexity across these modalities. Was there any subanalysis of AL rates by surgical approach? Moreover, while the application technique appears straightforward, it inevitably carries a learning curve. Standardization and reproducibility of the nebulization process (e.g., distance from the anastomosis, quantity applied, and area of coverage) are essential for widespread adoption but are not detailed in the manuscript. Could variability in application technique between surgeons and centers constitute an unrecognized confounder?
Fourth, the authors report a very low incidence of anastomotic bleeding (1.3%) and postoperative infection (3.9%), which they attribute to Glubran 2’s intrinsic properties. This is a valuable observation. A formal cost-effectiveness analysis would further enhance these findings. Although Glubran 2 entails an additional direct cost, if it reliably prevents even a small number of ALs, which are complications that can increase hospital costs by 2- to 5-fold, it would likely prove highly cost-effective. We encourage the authors to pursue such an analysis in future research.
In conclusion, Rega et al. [1] have presented compelling prospective data on a promising technology for anastomotic reinforcement. Their study convincingly demonstrates the feasibility and safety of Glubran 2 application and generates a strong hypothesis that it may significantly reduce AL. The observed AL rate of 1.85% represents an excellent outcome. However, the absence of a concurrent comparison group across different anastomotic sites means that the efficacy of Glubran 2, while highly plausible, remains to be definitively established.
Nevertheless, this study provides an important foundation for the essential next step: a large-scale, multicenter randomized controlled trial comparing ileocolic anastomoses with versus without Glubran 2 reinforcement and potentially extending to other anastomotic sites. We congratulate the authors on this valuable contribution and look forward to the continuation of this research.

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

  • 1. Rega D, Giulio E, Luca R, Muratore A, Milone M, Sica G, et al. Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study. Ann Coloproctol 2025;41:293–302. ArticlePubMedPMCPDF
  • 2. Hammond J, Lim S, Wan Y, Gao X, Patkar A. The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and economic outcomes. J Gastrointest Surg 2014;18:1176–85. ArticlePubMedPMCPDF
  • 3. Nordholm-Carstensen A, Schnack Rasmussen M, Krarup PM. Increased leak rates following stapled versus handsewn ileocolic anastomosis in patients with right-sided colon cancer: a nationwide cohort study. Dis Colon Rectum 2019;62:542–8. ArticlePubMed
  • 4. Espin E, Vallribera F, Kreisler E, Biondo S. Clinical impact of leakage in patients with handsewn vs stapled anastomosis after right hemicolectomy: a retrospective study. Colorectal Dis 2020;22:1286–92. ArticlePubMedPDF
  • 5. 2017 European Society of Coloproctology (ESCP) Collaborating Group. Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit. Colorectal Dis 2018;20 Suppl 6:15–32. ArticlePubMedPDF

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        Comments on “Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”
        Ann Coloproctol. 2025;41(6):596-597.   Published online December 29, 2025
        DOI: https://doi.org/10.3393/ac.2025.01137.0162
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