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Letter to the Editor
Complications
 In reply to: Comments on "Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”
Daniela Regaorcid, Carmela Cervoneorcid, Paolo Delrioorcid
Annals of Coloproctology 2025;41(6):598-599.
DOI: https://doi.org/10.3393/ac.2025.01452.0207
Published online: December 29, 2025

Division of Colorectal Surgical Oncology, Department of Abdominal Oncology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy

Correspondence to: Daniela Rega, MD Division of Colorectal Surgical Oncology, Department of Abdominal Oncology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, 52 Via Mariano Semmola, Naples 80131, Italy Email: d.rega@istitutotumori.na.it
• Received: November 30, 2025   • Accepted: November 30, 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 the article "Comments on “Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”" on page 596.
Dear Editor,
We sincerely thank Dr. Nabil Mohammad Azmi and colleagues for their interest in our study, “Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study” [1]. We welcome the opportunity to further clarify and expand on key aspects of our methodology and findings.
Regarding the historical benchmark for anastomotic leak (AL) rates, our protocol, preregistered and approved prior to enrollment, defined the reference AL rate (6.18%) based on Hammond et al.’s [2] large cohort (99,879 colorectal procedures). Although these data predate current surgical standards, the figure was selected for its statistical robustness and relevance at the time of study design. Notably, contemporary European series still report ileocolic AL rates between 3% and 12%, supporting the continued validity of our benchmark. We recognize that the historical nature of the comparator is a limitation, but it served as a fixed reference for our primary endpoint, a 50% reduction in AL incidence.
Our prospective, multicenter, observational study was intentionally designed without a control group to pragmatically assess the safety and feasibility of Glubran 2 (GEM Srl) in routine practice. All patients received the intervention, with outcomes reflecting real-world clinical scenarios. We acknowledge that this design limits causal inference and that future randomized controlled trials (RCTs) are necessary to confirm efficacy.
We appreciate the attention paid to the role of preoperative risk factors. Over 55% of patients in our cohort had at least one classical risk factor for AL (e.g., diabetes, smoking, or vascular disease), yet the overall AL rate was just 1.85%. Logistic regression did not identify any of these variables as significant predictors of leakage. While this finding is inherently vulnerable to confounding in an uncontrolled setting, it raises a clinically relevant hypothesis: that Glubran 2 may offer a protective effect even in high-risk scenarios. Our article carefully used the term “potentially mitigates” to reflect this exploratory signal. We fully agree that this observation requires validation in an appropriately stratified RCT, which we are actively planning.
Concerning the technical application, Glubran 2 was applied using a dedicated nebulizer specifically designed for open, laparoscopic, and robotic approaches. This ensured a standardized, thin, continuous film over the anastomotic line. All centers adhered to the same application protocol to ensure uniform technique.
Subgroup analysis did not reveal significant differences in AL rates based on surgical approach (open, laparoscopic, or robotic), anastomosis type (handsewn vs. stapled), or configuration (side-to-side, end-to-side, etc.). These findings suggest consistent benefit across modalities, although exploratory subgroup analyses are ongoing.
We also acknowledge the relevance of Glubran 2’s hemostatic and bacteriostatic properties. Its polymerization provides immediate sealing and a temporary antimicrobial barrier, potentially protective during the critical early healing phase. While our study was not powered to evaluate cost-effectiveness, we agree that this is a key dimension and have initiated a dedicated health economic analysis based on our multicenter data.
We thank Dr. Azmi and colleagues for their constructive remarks. We share their view that rigorous, controlled research is the next step. Our findings provide a valuable foundation, and we are optimistic that forthcoming RCTs will confirm the role of cyanoacrylate glue in enhancing anastomotic safety in colorectal surgery.

Conflict of interest

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

Funding

None.

Correction

This article was corrected on March 5, 2026, to fix a misspelling in the byline.

  • 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

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        In reply to: Comments on "Improved outcomes with cyanoacrylate glue for ileocolic anastomosis in right colectomy: a multicenter study”
        Ann Coloproctol. 2025;41(6):598-599.   Published online December 29, 2025
        DOI: https://doi.org/10.3393/ac.2025.01452.0207
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