Long-Term Safety and Efficacy of Alginate-Based Serosal Reinforcement (SEAL-G/SEAL-G MIST) Following Colorectal Anastomosis: A Multicenter, Comparative and Retrospective Cohort Study

<b>Background:</b> Anastomotic leakage (AL) remains a major complication following colorectal surgery (3-19% incidence, 6-39% mortality). SEAL-G/SEAL-G MIST are alginate-based sealants for anastomotic reinforcement. While short-term safety and efficacy feasibility have been established in a previous study, this study reports long-term results. <b>Methods:</b> A multicenter, retrospective and comparative study at three centers (Israel, Italy). Retrospective Treatment group: 79 patients from the original study treated with SEAL-G/SEAL-G MIST during elective colon cancer resection (2021-2023). Retrospective Control group: 86 comparative patients with standard technique. Primary endpoint: Incidence of long-term complications (adhesions, stenosis, stricture, obstruction) at 1 year. Secondary endpoints: Complications at 1-4 years and 30-day AL rate. Non-inferiority assessed via Farrington-Manning method (margin 0.10). <b>Results:</b> Mean follow-up: 3.3 ± 0.63 years (treatment) vs. 3.4 ± 1.10 years (control). Groups were comparable for demographics and surgical characteristics. Long-term complications at 1 year: 1.27% (1/79) vs. 2.33% (2/86); 90% CI for difference: -0.067 to 0.046, <i>p</i> = 0.0048 (non-inferiority confirmed). No stenosis or stricture occurred in either group. No additional complications emerged at 1-4 years in the treatment group. Thirty-day AL rate: 1.27% (1/79) vs. 5.68% (5/88); all subclinical leaks (Grade B, n = 4) occurred in controls. <b>Conclusions:</b> Serosal reinforcement with alginate-based sealants does not introduce device-related long-term complications following colorectal anastomosis. The favorable short-term safety profile extends to 2-4 years. These findings support the safety of alginate-based sealants as anastomotic adjuncts, consistent with the paradigm of leak containment and severity reduction.