Efficacy and safety of novel alginate-based sealants (SEAL-G and SEAL-G MIST) in reducing anastomotic leakage following colorectal anastomosis: a prospective multicenter study

Moshe Kamar; Fahim Kanani; Antonio Spinelli; David Jayne; Lior Segev; Matt Tutton; Isacco Montroni; Hagit Tulchinsky; Mordechai Shimonov; Ron Lavy; Oded Zmora

doi:10.3393/ac.2025.00297.0042

Articles

Page Path: HOME > Ann Coloproctol > Volume 41(5); 2025 > Article

Original Article Complications Efficacy and safety of novel alginate-based sealants (SEAL-G and SEAL-G MIST) in reducing anastomotic leakage following colorectal anastomosis: a prospective multicenter study: Moshe Kamar^1,*, Fahim Kanani^1,2,*, Antonio Spinelli^3,4, David Jayne⁵, Lior Segev⁶, Matt Tutton⁷, Isacco Montroni^8,9, Hagit Tulchinsky², Mordechai Shimonov¹, Ron Lavy¹⁰, Oded Zmora¹⁰; Annals of Coloproctology 2025;41(5):424-433.
DOI: https://doi.org/10.3393/ac.2025.00297.0042
Published online: October 23, 2025

¹Surgical Department, Wolfson Medical Center, Holon, Israel

²Colorectal Unit, Surgical Department, Ichilov Medical Center, Tel Aviv, Israel

³Department of General Surgery and Colorectal Unit, IRCCS Humanitas Research Hospital, Milan, Italy

⁴Department of Biomedical Sciences, Humanitas University, Milan, Italy

⁵Department of General Surgery and Colorectal Unit, St James's Hospital, Leeds, UK

⁶Colorectal Unit, Surgical Department, Sheba Tel Ha-Shomer Medical Center, Ramat Gan, Israel

⁷Department of General Surgery and Colorectal Unit, Colchester General Hospital, Colchester, UK

⁸Colorectal Surgery Unit, Ospedale S. Maria delle Croci, Ravenna, Italy

⁹Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

¹⁰Surgical Department, Shamir Medical Center, Beer Yackov, Israel

Correspondence to: Moshe Kamar, MD Surgical Department, Wolfson Medical Center, Holon, Israel Email: moshekam@wmc.gov.il
Co-correspondence to: Fahim Kanani, MD Surgical Department, Wolfson Medical Center, Holon, Israel Email: kanani.fahim@gmail.com

*Moshe Kamar and Fahim Kanani contributed equally to this study as co-first authors.

• Received: March 19, 2025 • Revised: June 10, 2025 • Accepted: June 12, 2025

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.

prev next

5,650 Views
89 Download
1 Web of Science
1 Crossref
1 Scopus

Full Article

Download PDF

Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
Supplementary materials
REFERENCES

Abstract

Purpose
This study aimed to evaluate the efficacy, usability, and safety of the novel alginate-based sealants SEAL-G and SEAL-G MIST in reducing anastomotic leakage after colorectal resection.
Methods
This prospective, multicenter study enrolled 160 patients undergoing elective colonic resection with primary anastomosis at 8 centers. SEAL-G was applied in open procedures (n=33), and SEAL-G MIST was used for minimally invasive procedures (n=127), with both sealants applied circumferentially to the anastomotic site. The primary endpoints included the rate of anastomotic coverage and the incidence of leakage within 30 days, classified according to the International Study Group of Rectal Cancer (ISGRC) criteria.
Results
The overall anastomotic leak rate was 3.1% (5 of 160), with only 1 patient (0.6%) experiencing a grade C leak that required reoperation. Four patients (2.5%) developed grade A or B leaks, all of which were managed conservatively. Complete circumferential sealant coverage was achieved in 93.1% of cases. The overall leak rates for SEAL-G and SEAL-G MIST groups were 6.1% and 2.4%, respectively. However, statistical analysis did not show a significant difference. Mean hospital stay was significantly shorter after laparoscopic surgery compared to open surgery (5.1±2.8 days vs. 8.4±5.5 days, P<0.001).
Conclusion
Alginate-based sealants show promise in reducing the severity of anastomotic leaks and in supporting anastomotic healing, demonstrating high technical success and low complication rates.
Trial registration
ClinicalTrials.gov identifier: NCT04532515
Keywords: Colorectal surgery; Anastomotic leak; Tissue adhesives; Wound healing; Patient safety

INTRODUCTION

Anastomotic leakage (AL) remains the most serious complication in colorectal surgery, resulting in severe clinical and economic consequences despite advances in surgical technique and perioperative care [1]. The reported incidence of AL ranges from 1.8% to 19.2%, depending on the anatomical location, with rectal anastomoses showing a substantially higher risk (up to 24%) compared to colonic anastomoses (2.4%–6.8%) [1–3]. In addition to immediate septic complications, AL increases mortality by 6% to 39%, lengthens hospital stays by a factor of 2.4 to 5.3, and raises healthcare costs by €37,609 to €71,940 per affected patient [4–8]. Moreover, AL negatively impacts oncologic outcomes, with meta-analyses indicating higher local recurrence rates (hazard ratio, 1.90) and reduced overall survival among cancer patients [9–13]. Leakage arises from both mechanical and biological factors that compromise anastomotic integrity, often worsened by tissue hypoxia, which impedes collagen synthesis and disrupts the inflammatory response. Established risk factors include male sex, advanced age, malnutrition, smoking, comorbidities such as diabetes and cardiovascular disease, and procedural aspects including left-sided anastomoses, emergency surgery, and prolonged operating time. Early detection using biomarkers (e.g., C-reactive protein, procalcitonin) and a multifaceted preventive strategy may help avert severe septic sequelae [6, 14–16].

Current preventive strategies focus on patient optimization, meticulous surgical technique, and selective fecal diversion. While temporary stomas can reduce the clinical impact of leakage in high-risk patients, they introduce additional morbidity, necessitate subsequent reversal, and can diminish quality of life [17]. Similarly, mechanical bowel preparation has shown limited benefit in randomized trials, with several studies finding no significant reduction in leak rates [18, 19]. These limitations underscore the need for alternative approaches to reinforce anastomotic integrity.

Various tissue sealants and adhesives have been investigated as adjuncts to standard anastomotic techniques. Fibrin sealants, initially developed for hemostasis, have yielded inconsistent results in leak prevention [20–23]. Cyanoacrylate-based adhesives offer effective sealing properties but can elicit significant foreign body reactions and inflammatory responses that may paradoxically impair healing [4, 24–26]. Despite technical progress in surgery, AL rates have remained relatively unchanged over the last 2 decades [27, 28], highlighting the necessity for novel solutions that address biomechanical weaknesses while supporting biological healing. The ideal anastomotic sealant should provide mechanical support without hindering physiological healing [29].

Alginate-based sealants represent a novel strategy for anastomotic reinforcement, forming a watertight barrier that mechanically adheres to tissue irregularities without inducing chemical or biological interaction, thereby avoiding significant inflammation [30, 31]. Seal-G (Advanced Medical Solutions) and Seal-G MIST are formulated for extraluminal application, with Seal-G MIST (Advanced Medical Solutions) specifically designed for minimally invasive delivery using a flexible 40-cm cannula. Preclinical studies have demonstrated that these sealants offer effective sealing and are gradually resorbed over 3 to 4 months through macrophage phagocytosis [28–31], thus providing temporary protection during the critical healing period without leaving a permanent foreign body.

This prospective multicenter study was designed to evaluate the safety, feasibility, and efficacy of SEAL-G and SEAL-G MIST alginate-based sealants for reinforcing colorectal anastomoses. We hypothesized that these new formulations would decrease both the incidence and severity of AL in patients undergoing elective colonic resection with primary anastomosis by offering mechanical protection throughout the vulnerable period of healing.

METHODS

Ethics statements

This multicenter, single-arm, prospective study was conducted at 8 centers in Italy, the United Kingdom, and Israel. The study protocol received approval from all local institutional review boards (No. DLG-072-06) and was registered on ClinicalTrials.gov (identifier: NCT04532515). Written informed consent was obtained from all participants before enrollment. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Study design and patient selection

A total of 189 patients were screened for eligibility between 2021 and 2023. Of these, 160 patients (84.7%) met the inclusion criteria and received the alginate-based sealant. Twenty-nine patients were excluded before sealant application: 16 were excluded during preoperative screening, and 13 were excluded intraoperatively after meeting exclusion criteria, most commonly due to metastatic disease or an anastomosis located less than 10 cm from the anal verge. Patient recruitment and flow are illustrated in Fig. 1 in accordance with CONSORT (Consolidated Standards of Reporting Trials) guidelines.

Inclusion and exclusion criteria

Adult patients (≥18 years) with histologically confirmed colon adenocarcinoma scheduled for elective colonic resection with primary anastomosis were eligible. Preoperative exclusion criteria included rectal cancer (tumor less than 9 cm from the anal verge), inflammatory bowel disease, synchronous colorectal tumors, radiologically confirmed metastatic disease, or an American Society of Anesthesiologists (ASA) physical status classification greater than III.

Intraoperative exclusion criteria comprised metastatic disease identified via imaging, clinical assessment, or biomarkers; unexpected metastatic disease discovered during surgical exploration; anastomosis less than 10 cm from the anal verge; multiple anastomoses; intraoperative transfusion of more than 2 units of packed cells; and use of any other sealant in addition to Seal-G. Patients with known hypersensitivity to indigo carmine dye were also excluded.

Preoperative assessment and surgical procedure

All patients underwent a standard preoperative assessment, including clinical examination, laboratory testing, colonoscopy with biopsy, and radiological staging. Preoperative mechanical bowel preparation was administered according to each site’s standard of care. Both oral antibiotic prophylaxis and venous thromboembolism prophylaxis were given per institutional protocols.

Surgical procedures were performed via open, laparoscopic, or robotic approaches based on surgeon preference and expertise. Technical aspects of the operation, including vascular approach, resection extent, and anastomotic technique (hand-sewn or stapled), followed the center’s standard practices. No patients received proximal fecal diversion.

Intervention: SEAL-G and SEAL-G MIST technology

After the creation of the colorectal anastomosis, SEAL-G, an alginate-based surgical sealant, was applied as an adjunct to standard anastomotic techniques. This technology uses a marine-derived polymer to create a strong, flexible seal that acts as a mechanical “seatbelt” around the anastomosis. The sealant reaches full sealing strength within 60 seconds, providing robust support during the critical postoperative healing period while allowing for normal peristalsis.

Two delivery systems were utilized based on the surgical approach:

(1) SEAL-G Open: For open procedures involving extracorporeal anastomoses, a double-syringe device with a short tip containing alginate solution and calcium carbonate cross-linker was applied directly to the serosal surface using a spreading technique.

(2) SEAL-G MIST: For minimally invasive procedures with intracorporeal anastomoses, an identical alginate and cross-linker composition was delivered using a 40-cm cannula with a flexible tip, designed for laparoscopic or robotic access. The sealant was sprayed using CO₂ delivered via a gas regulator (Fibrijet Flow regulator SA-6045, Nordson Micromedics) at a flow rate of 3 to 4 L/min, with care taken to avoid direct spraying into open vessels to prevent gas embolism.

Both formulations contained indigo carmine to enhance visualization, producing a thin blue gel layer over the anastomotic site. The surgeon applied the sealant circumferentially, covering the anastomotic line and adjacent serosa (approximately 1–2 cm on either side). The technical application process is demonstrated in Fig. 2 [32] and Supplementary Video 1.

Circumferential coverage was assessed intraoperatively by the surgeon through visual inspection and photographic documentation. Complete coverage was defined as a continuous blue layer of sealant visible around the entire anastomosis. Photographic records were obtained in all cases for subsequent verification.

Postoperative care and outcome assessment

Postoperative management adhered to each center’s enhanced recovery protocols. Patients were followed for 30 days postoperatively (±7-day window) with scheduled clinical evaluations. Follow-up included assessment of clinical status, laboratory tests, and radiological investigations as clinically indicated.

The incidence of AL within 30 days was evaluated using the International Study Group of Rectal Cancer (ISREC) criteria, classifying leaks as grade A (requiring no management change), grade B (requiring nonsurgical intervention), or grade C (requiring reoperation). Secondary endpoints included the overall complication rate, length of hospital stay, readmission rate, mortality, and technical success of sealant application. Postoperative complications were graded according to the Clavien-Dindo classification.

Statistical analysis

Continuous variables were reported as mean±standard deviation or as median and interquartile range, as appropriate, and categorical variables as frequencies and percentages. Comparisons between SEAL-G and SEAL-G MIST groups used the t-test for continuous variables and chi-square or Fisher exact tests for categorical variables, as appropriate.

The sample size was determined based on the primary endpoint of AL. Assuming a reduction in AL rate from the historical average of 8.6% to 3.0%, with 80% power and a 2-sided α of 0.05, a minimum of 151 patients was required. Allowing for a 5% dropout rate, we planned to enroll 160 patients.

The observed AL rate was compared with historical data from large, published registry studies, which report an average leak rate of 8.6% in colorectal surgery, to assess the potential benefit of the alginate-based sealant in reducing leak incidence. All statistical analyses were performed using IBM SPSS ver. 28 (IBM Corp), with a P-value of <0.05 considered statistically significant.

RESULTS

Patient demographics and baseline characteristics

Of the 189 patients screened for eligibility, 160 (84.7%) met the inclusion criteria and received the alginate-based sealant. Twenty-nine patients were excluded before treatment application: 16 during preoperative screening and 13 intraoperatively, primarily due to metastatic disease or an anastomosis located less than 10 cm from the anal verge. The cohort had a mean age of 66.7±9.5 years, with 87 men (54.4%) and 73 women (45.6%). The mean body mass index was 27.1±4.1 kg/m². The majority of patients had right-sided tumors (96 patients, 60.0%) and an ASA physical status II (103 patients, 64.4%). Most tumors were stage III (70 patients, 43.8%). Detailed patient demographics and tumor characteristics are shown in Table 1.

Surgical procedures and technical outcomes

Right hemicolectomy was the most common procedure (95 patients, 59.4%), followed by sigmoidectomy (25 patients, 15.6%) and left colectomy (24 patients, 15.0%). A minimally invasive approach was utilized in 149 patients (93.1%), with intracorporeal anastomosis performed in 127 patients (79.4%) (Table 2). Seal-G was used in 33 patients (20.6%) for open or extracorporeal anastomoses, while Seal-G MIST was applied in 127 patients (79.4%) for intracorporeal anastomoses.

Surgeons reported successful circumferential coverage of the anastomosis in 149 patients (93.1%). The most common reason for incomplete coverage was limited visibility of the posterior aspect of the anastomosis, making assessment and application challenging.

Clinical outcomes and AL rates

The overall AL rate was 3.1% (5 of 160). Only 1 patient (0.6%) experienced a grade C leak requiring reoperation on postoperative day 2. Four patients (2.5%) developed grade A or B leaks that were managed conservatively. Leak rates were comparable between the SEAL-G and SEAL-G MIST groups (6.1% vs. 2.4%, P=0.280) (Table 3).

Postoperative recovery and complications

The mean length of hospital stay was significantly shorter after SEAL-G MIST than after SEAL-G (5.1±2.8 days vs. 8.4±5.5 days, P<0.001) (Table 3). No treatment-related adverse events attributable to the sealant were reported. All patients completed the 30-day follow-up period, and there were no mortalities or readmissions.

DISCUSSION

This prospective, multicenter study demonstrates that alginate-based sealants (SEAL-G and SEAL-G MIST) can be safely and effectively applied to colorectal anastomoses, achieving high technical success rates. Key findings include a low overall AL rate of 3.1%, with only 0.6% of patients requiring reoperation for grade C leaks. Complete circumferential sealant coverage was achieved in 93.1% of cases, with comparable results between open (Seal-G) and minimally invasive (Seal-G MIST) applications. These results suggest that alginate-based sealants may contribute to reducing the clinical impact of AL through mechanical reinforcement and containment of potential leaks.

While fundamental surgical principles remain essential for anastomotic integrity, our findings suggest that external reinforcement with alginate-based sealants offers a promising adjunctive strategy. Unlike previous tissue adhesives and sealants that showed inconsistent results, our observed AL rate of 3.1% compares favorably to the 2% to 19% range reported in the literature [3]. Particularly noteworthy is the remarkably low rate of grade C leaks requiring reoperation (0.6%), suggesting that the sealant may effectively contain minor leakage and prevent progression to clinically significant complications. This is consistent with the hypothesis that mechanical reinforcement provides additional protection during the vulnerable healing phase, potentially offsetting technical and biological risk factors that might otherwise lead to anastomotic failure.

Our study was fundamentally grounded in a novel approach to leak management—namely, reducing the clinical significance of AL by providing a mechanism to contain and potentially downgrade severe leaks. The results are promising, with only 0.6% of leaks requiring surgical intervention (grade C) and 2.5% classified as grade A or B. These rates are substantially lower than those previously reported in colorectal surgery, where comparable procedures typically demonstrate 0.3% to 1.9% grade A and B leaks out of an overall 4.8% to 8.7% leak incidence [6, 8, 9]. Large registry audits have consistently reported AL rates as high as 8.1% in right hemicolectomy and 8.5% in left-sided colectomy or rectal resection [7]. Moreover, the reoperation rate was significantly lower in our study compared to other large studies demonstrating improvements in leak management (Table 4) [33–35]. The ANACO Study Group in Spain reported the highest total leak rate of 10.6% [35], while the SEAL-G Study observed the lowest rate at 3.1%. The Dutch Institute for Colorectal Audit (DICA) [34] and the Italian ColoRectal Anastomotic Leakage (iCral) Study Group [33] represent intermediate positions, reflecting evolving surgical techniques and postoperative care in colorectal surgery (Fig. 3).

The mechanical properties of the alginate-based sealants likely contributed to the favorable outcomes observed in our study. The SEAL-G formulation is completely free of human or animal components and is fully resorbable without producing toxic degradation by-products. Preclinical studies have demonstrated superior burst strength (143 mmHg) compared to commercially available alternatives, such as fibrin sealant patch (45 mmHg) and fibrin sealant (15 mmHg). This superior burst strength provides robust mechanical reinforcement to the anastomosis during the critical healing period, which may help explain the lower rate of grade C leaks requiring reoperation observed in our cohort compared to historical controls.

Furthermore, histological analysis has shown that by postoperative day 14, the sealant and surrounding fibrotic tissue completely encapsulate the anastomotic site, with more than 50% biodegradation by 3 months after implantation through phagocytic activity. These histological findings are particularly relevant, as this timeframe corresponds to the period when most ALs develop. Gradual biodegradation through phagocytic activity suggests that the sealant provides protection during the vulnerable healing phase without creating a permanent foreign body that might induce long-term complications. This balanced profile of mechanical support and biocompatibility may explain the clinical outcomes observed in our patient cohort.

The technical application of the sealant also represents a notable advancement, with a remarkable 93.8% rate of full coverage. This high rate highlights the ease and feasibility of use and underscores the potential of the alginate-based sealant to effectively reinforce anastomotic integrity by mechanically adhering to and covering suture lines. This was enabled by 2 ergonomic features: first, the blue coloration of the sealant allowed the surgeon to immediately identify any uncovered areas in real time; and second, the spray application method facilitated coverage of even difficult-to-access regions of the anastomosis. The mechanical properties of the Seal-G products thus appear to provide a unique approach to supporting the anastomotic healing process, potentially establishing a protective barrier that can contain or minimize leak progression without increasing the risk of adverse events such as stenosis or infection due to foreign bodies.

However, methodological limitations must be acknowledged. The study’s single-arm design represents the most significant limitation and warrants detailed discussion. Without a concurrent control group, we cannot definitively attribute the observed low leak rates to the sealant intervention alone. Several factors inherent to single-arm designs may influence our findings: selection bias in patient enrollment, the potential Hawthorne effect (where surgical teams may perform procedures more meticulously when participating in a clinical trial) and the inability to control for temporal improvements in perioperative care protocols. While our comparison to historical registry data provides useful context, we acknowledge that such comparisons cannot account for all confounding variables, including evolving surgical techniques, Enhanced Recovery After Surgery (ERAS) protocols, and improvements in patient selection over time.

The relatively modest sample size of 160 patients further limits the precision of our estimates and restricts subgroup analyses that might identify specific patient populations most likely to benefit from sealant application. Additionally, the single-arm design precludes a cost-effectiveness analysis, which would be crucial for healthcare systems considering adoption of this technology.

While the multicenter, prospective approach confers some robustness to the findings, definitive conclusions require further investigation. We view this study as hypothesis-generating rather than confirmatory, providing essential safety and feasibility data to justify and inform the design of future randomized controlled trials. Future research must prioritize randomized controlled trials with larger, more diverse patient cohorts to comprehensively evaluate the sealant’s efficacy. These studies should attempt to clarify specific patient profiles most likely to benefit from Seal-G applications and to validate the potential of this approach in reducing anastomotic leak severity and clinical impact. Until such evidence becomes available, our findings should be interpreted with appropriate caution, recognizing that the promising results observed may be influenced by the inherent limitations of our study design.

Conclusions

Alginate-based sealants, such as SEAL-G and SEAL-G MIST, represent a promising biologic approach to anastomotic reinforcement. Surgeons should continue to emphasize meticulous preoperative optimization, precise intraoperative technique, and adherence to enhanced recovery protocols. Nevertheless, anastomotic leaks remain an inevitable risk, highlighting the need for strategies that minimize their clinical impact—particularly reoperations and stoma formation. Extraluminal serosal reinforcement, ideally implemented without increasing the risk of stenosis or infection, may help contain leaks and thereby improve patients’ quality of life. Given that AL rates have remained largely unchanged over the past 2 decades, innovative solutions that address biomechanical vulnerabilities while supporting optimal healing are crucial. We advocate for a paradigm shift in the conceptual approach to AL-related complications in future research; rather than focusing solely on reducing overall leak rates, future studies should prioritize reducing the incidence of grade C ALs.

ARTICLE INFORMATION

Conflict of interest

The sealant technology was provided by Advanced Medical Solutions. However, the surgical procedures, patient selection, and clinical assessments were conducted independently by the participating medical centers, ensuring unbiased scientific evaluation. While the technology provider supplied the sealant, they had no influence on surgical techniques, patient management, or data analysis. No other potential conflict of interest relevant to this article was reported.

Funding

None.

Acknowledgments

The authors thank the contributions of participating medical centers, research teams, technology providers, and patient volunteers who made this study possible.

Author contributions

Conceptualization: all authors; Data curation: all authors; Formal analysis: MK, FK, OZ; Investigation: all authors; Methodology: MK, FK, AS, DJ, OZ; Project administration: MK, FK, OZ; Resources: AS, DJ, LS, MT, IM, HT, MS, RL; Software: MK, FK; Supervision: AS, DJ, HT, MS, RL, OZ; Validation: MK, FK, AS, OZ; Visualization: MK, FK; Writing–original draft: MK, FK; Writing–review & editing: all authors; All authors read and approved the final manuscript.

Supplementary materials

Supplementary Video 1.

SEAL-G application method.

Supplementary materials are available from https://doi.org/10.3393/ac.2025.00297.0042.

Fig. 1.

CONSORT (Consolidated Standards of Reporting Trials) flowchart of the study. ^aAdvanced Medical Solutions.

Fig. 2.

SEAL-G surgical sealant system (Advanced Medical Solutions) and delivery mechanism. The SEAL-G dual-syringe delivery system for intraoperative application of surgical hydrogel sealant is shown. The system utilizes 2 components: alginate with calcium carbonate (cross-linker) and alginate with acetate (trigger), which mix upon activation via a CO₂ (Luer) propellant to rapidly form a hydrogel. Two delivery tips are available: an atraumatic mixer tip for precise application and a block-resistant spray tip for broader coverage. Cannulae are available in both 20 cm and 40 cm lengths. The system delivers 4 mL of sealant with a 60-second curing time and a 1-hour working window. Reprinted with permission from Advanced Medical Solutions [32].

Fig. 3.

Comprehensive anastomotic leak (AL) rates from 4 major colorectal surgery studies. Reoperation rate is low in the SEAL-G Study compared to other studies. Together, these results reflect an evolving landscape of surgical techniques and postoperative care in colorectal surgery. DICA, Dutch Institute for Colorectal Audit; iCral, Italian ColoRectal Anastomotic Leakage.

Table 1.

Patient demographics and baseline characteristics

Characteristic	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)	P-value^b
Age (yr)	68.5 (31.4–84.4)	70.3 (47.2–80.8)	68.5 (31.4–84.4)	0.338
Sex				0.338
Male	87 (54.4)	15 (45.5)	72 (56.7)
Female	73 (45.6)	18 (54.5)	55 (43.3)
Body mass index (kg/m²)	26.7 (17.9–43.3)	28.2 (19.6–37.4)	26.7 (17.9–41.0)	0.059
Tumor location				0.458
Right colon	96 (60.0)	20 (60.6)	76 (59.8)
Left colon	27 (16.9)	8 (24.2)	19 (15.0)
Sigmoid	36 (22.5)	5 (15.2)	31 (24.4)
Upper rectum	1 (0.6)	0 (0)	1 (0.8)
Tumor stage				0.400
I	17 (10.6)	4 (12.1)	13 (10.2)
II	51 (31.9)	7 (21.2)	44 (34.6)
III	70 (43.8)	19 (57.6)	51 (40.2)
IV	7 (4.4)	1 (3.0)	6 (4.7)
Unknown	15 (9.4)	2 (6.1)	13 (10.2)
ASA physical status				0.589
I	10 (6.3)	3 (9.1)	7 (5.5)
II	103 (64.4)	19 (57.6)	84 (66.1)
III	47 (29.4)	11 (33.3)	36 (28.3)

Values are presented as median (interquartile range) or number (%).

ASA, American Society of Anesthesiologists.

^aAdvanced Medical Solutions.

^bP-values for comparison between SEAL-G and SEAL-G MIST groups, calculated using t-test for continuous variables and the chi-square or Fisher exact test for categorical variables as appropriate.

Table 2.

Surgical characteristics and procedures

Characteristic	No. of patients (%)
Characteristic	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)
Procedure type
Right hemicolectomy	95 (59.4)	21 (63.6)	74 (58.3)
Left colectomy	24 (15.0)	5 (15.2)	19 (15.0)
Sigmoidectomy	25 (15.6)	4 (12.1)	21 (16.5)
Anterior resection	12 (7.5)	3 (9.1)	9 (7.1)
Subtotal colectomy	4 (2.5)	0 (0)	4 (3.1)
Surgical approach
Open	11 (6.9)	11 (33.3)	0 (0)
Laparoscopic/robotic	149 (93.1)	22 (66.7)	127 (100)
Anastomotic technique
Extracorporeal	22 (13.8)	20 (60.6)	2 (1.6)
Intracorporeal	127 (79.4)	2 (6.1)	125 (98.4)
Open	11 (6.9)	11 (33.3)	0 (0)
Sealant application
Complete circumferential coverage	149 (93.1)	31 (93.9)	118 (92.9)
Partial coverage	11 (6.9)	2 (6.1)	9 (7.1)

^aAdvanced Medical Solutions.

Table 3.

Clinical outcomes

Outcome	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)	P-value^b
Anastomotic leak				0.280
Overall	5 (3.1)	2 (6.1)	3 (2.4)
Grade A/B	4 (2.5)	1 (3.0)	3 (2.4)
Grade C	1 (0.6)	1 (3.0)	0 (0)
Length of hospital stay (day)	5.8±3.7	8.4±5.5	5.1±2.8	<0.001
Time to leak diagnosis (day)	6.0±2.3	4.5±1.8	7.0±2.7	-
Reoperation^c	1 (0.6)	1 (3.0)	0 (0)	-
30-day Readmission	0 (0)	0 (0)	0 (0)	-
30-day Mortality	0 (0)	0 (0)	0 (0)	-

Values are presented as number (%), mean±standard deviation, or number only. Tumor stages are reported according to pathological staging (pTNM) following surgical resection.

^aAdvanced Medical Solutions.

^bP-values for comparison between SEAL-G and SEAL-G MIST groups; calculated using t-test for continuous variables and the chi-square or Fisher exact test for categorical variables as appropriate.

^cOnly 1 patient in the Seal-G group had a grade C leak requiring reoperation.

Table 4.

Comparison of AL between this study and national colonic studies

Study	Country	Reoperation (%)	Management without reoperation (%)	Total AL rate (%)
ANACO Study Group [34]	Spain	8.7	1.9	10.6
DICA [33]	The Netherlands	6.9	2.0	8.9
iCral Study Group [32]	Italy	4.8	1.6	6.4
This study	-	0.6	2.5	3.1

AL, anastomotic leak; DICA, Dutch Institute for Colorectal Audit; iCral, Italian ColoRectal Anastomotic Leakage.

REFERENCES

1. Kirchhoff P, Clavien PA, Hahnloser D. Complications in colorectal surgery: risk factors and preventive strategies. Patient Saf Surg 2010;4:5.Article PubMed PMC PDF
2. Rennie O, Sharma M, Helwa N. Colorectal anastomotic leakage: a narrative review of definitions, grading systems, and consequences of leaks. Front Surg 2024;11:1371567.Article PubMed PMC
3. Rahbari NN, Weitz J, Hohenberger W, Heald RJ, Moran B, Ulrich A, et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery 2010;147:339–351. Article PubMed
4. Wu Z, Vakalopoulos KA, Boersema GS, Kroese LF, Lam KH, van der Horst PH, et al. The prevention of colorectal anastomotic leakage with tissue adhesives in a contaminated environment is associated with the presence of anti-inflammatory macrophages. Int J Colorectal Dis 2014;29:1507–1516. Article PubMed PDF
5. Gené-Škrabec C, Cremades M, Fernández-Pujol A, Cortinovis S, Corral J, Julián JF, et al. Clinical results after external reinforcement of colorectal anastomosis: a systematic review. Int J Surg 2023;109:4322–4332. Article PubMed PMC
6. Yun JA, Cho YB, Park YA, Huh JW, Yun SH, Kim HC, et al. Clinical manifestations and risk factors of anastomotic leakage after low anterior resection for rectal cancer. ANZ J Surg 2017;87:908–914. Article PubMed PDF
7. van Rooijen SJ, Jongen AC, Wu ZQ, Ji JF, Slooter GD, Roumen RM, et al. Definition of colorectal anastomotic leakage: a consensus survey among Dutch and Chinese colorectal surgeons. World J Gastroenterol 2017;23:6172–6180. Article PubMed PMC
8. Gessler B, Eriksson O, Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis 2017;32:549–556. Article PubMed PMC PDF
9. Park JS, Huh JW, Park YA, Cho YB, Yun SH, Kim HC, et al. Risk factors of anastomotic leakage and long-term survival after colorectal surgery. Medicine (Baltimore) 2016;95:e2890. Article PubMed PMC
10. Branagan G, Finnis D. Prognosis after anastomotic leakage in colorectal surgery. Dis Colon Rectum 2005;48:1021–1026. Article PubMed
11. McArdle CS, McMillan DC, Hole DJ. Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer. Br J Surg 2005;92:1150–1154. Article PubMed PDF
12. Chiarello MM, Fransvea P, Cariati M, Adams NJ, Bianchi V, Brisinda G, et al. Anastomotic leakage in colorectal cancer surgery. Surg Oncol 2022;40:101708.Article PubMed
13. Kang CY, Halabi WJ, Chaudhry OO, Nguyen V, Pigazzi A, Carmichael JC, et al. Risk factors for anastomotic leakage after anterior resection for rectal cancer. JAMA Surg 2013;148:65–71. Article PubMed
14. Suzuki N, Yoshida S, Tomochika S, Nakagami Y, Shindo Y, Tokumitsu Y, et al. Determining the protective characteristics and risk factors for the development of anastomotic leakage after low anterior resection for rectal cancer. Surg Today 2021;51:713–720. Article PubMed PMC PDF
15. Sripathi S, Khan MI, Patel N, Meda RT, Nuguru SP, Rachakonda S, et al. Factors contributing to anastomotic leakage following colorectal surgery: why, when, and who leaks? Cureus 2022;14:e29964. Article PubMed PMC
16. Eberl T, Jagoditsch M, Klingler A, Tschmelitsch J. Risk factors for anastomotic leakage after resection for rectal cancer. Am J Surg 2008;196:592–598. Article PubMed
17. Hanna MH, Vinci A, Pigazzi A. Diverting ileostomy in colorectal surgery: when is it necessary? Langenbecks Arch Surg 2015;400:145–152. Article PubMed PDF
18. Wong NY, Eu KW. A defunctioning ileostomy does not prevent clinical anastomotic leak after a low anterior resection: a prospective, comparative study. Dis Colon Rectum 2005;48:2076–2079. Article PubMed
19. Bax TW, McNevin MS. The value of diverting loop ileostomy on the high-risk colon and rectal anastomosis. Am J Surg 2007;193:585–588. Article PubMed
20. Ma GW, Kucey A, Tyagi SC, Papia G, Kucey DS, Varcoe RL, et al. The role of sealants for achieving anastomotic hemostasis in vascular surgery. Cochrane Database Syst Rev 2024;5:CD013421.Article PubMed PMC
21. Daud A, Kaur B, McClure GR, Belley-Cote EP, Harlock J, Crowther M, et al. Fibrin and thrombin sealants in vascular and cardiac surgery: a systematic review and meta-analysis. Eur J Vasc Endovasc Surg 2020;60:469–478. Article PubMed
22. Rogers AC, Turley LP, Cross KS, McMonagle MP. Meta-analysis of the use of surgical sealants for suture-hole bleeding in arterial anastomoses. Br J Surg 2016;103:1758–1767. Article PubMed PDF
23. Vakalopoulos KA, Daams F, Wu Z, Timmermans L, Jeekel JJ, Kleinrensink GJ, et al. Tissue adhesives in gastrointestinal anastomosis: a systematic review. J Surg Res 2013;180:290–300. Article PubMed
24. Vakalopoulos KA, Bosmans JW, van Barneveld KW, Vogels RR, Boersema GS, Wu Z, et al. Impact of tissue adhesives on the prevention of anastomotic leakage of colonic anastomoses: an in vivo study. Int J Colorectal Dis 2017;32:961–965. Article PubMed PMC PDF
25. Valsamidis TN, Rasmussen T, Eriksen JD, Iversen LH. The role of tissue adhesives and sealants in colorectal anastomotic healing: a scoping review. Int J Colorectal Dis 2023;38:265.Article PubMed PDF
26. Tomasicchio G, Martines G, Tartaglia N, Buonfantino M, Restini E, Carlucci B, et al. Suture reinforcement using a modified cyanoacrylate glue to prevent anastomotic leak in colorectal surgery: a prospective multicentre randomized trial: the Rectal Anastomotic seaL (ReAL) trial. Tech Coloproctol 2024;28:95.Article PubMed PMC
27. 2017 European Society of Coloproctology (ESCP) Collaborating Group. The 2017 European Society of Coloproctology (ESCP) international snapshot audit of left colon, sigmoid and rectal resections: executive summary. Colorectal Dis 2018;20 Suppl 6:13–14. Article PubMed
28. 2015 European Society of Coloproctology Collaborating Group. The impact of stapling technique and surgeon specialism on anastomotic failure after right-sided colorectal resection: an international multicentre, prospective audit. Colorectal Dis 2018;20:1028–1040. Article PubMed PDF
29. Scognamiglio F, Travan A, Rustighi I, Tarchi P, Palmisano S, Marsich E, et al. Adhesive and sealant interfaces for general surgery applications. J Biomed Mater Res B Appl Biomater 2016;104:626–639. Article PubMed
30. de la Portilla F, García-Cabrera AM, Pereira S, de Marco F, Molero M, Muntane J, et al. An experimental study on the use of calcium alginate to heal colonic anastomoses. J Invest Surg 2016;29:32–39. Article PubMed
31. de la Portilla F, Dios-Barbeito S, Maestre-Sánchez MV, Vázquez-Monchul JM, García-Cabrera AM, Ramallo I, et al. Feasibility and safety of calcium alginate hydrogel sealant for the treatment of cryptoglandular fistula-in-ano: phase I/IIa clinical trial. Colorectal Dis 2021;23:1499–1506. Article PubMed PDF
32. Advanced Medical Solutions. Surgical sealants [Internet]. Advanced Medical Solutions Group; c2025 [cited 2025 Jun 4]. Available from: https://admedsol.com/products/surgical/adhesives-and-sealants/surgical-sealants/
33. Italian ColoRectal Anastomotic Leakage (iCral) study group. Colorectal surgery in Italy: a snapshot from the iCral study group. Updates Surg 2019;71:339–347. Article PubMed PDF
34. Van Leersum NJ, Snijders HS, Henneman D, Kolfschoten NE, Gooiker GA, ten Berge MG, et al. The Dutch Surgical Colorectal Audit. Eur J Surg Oncol 2013;39:1063–1070. Article PubMed
35. Frasson M, Flor-Lorente B, Rodríguez JL, Granero-Castro P, Hervás D, Alvarez Rico MA, et al. Risk factors for anastomotic leak after colon resection for cancer: multivariate analysis and nomogram from a multicentric, prospective, national study with 3193 patients. Ann Surg 2015;262:321–330. Article PubMed

Figure & Data

References

Citations

Citations to this article as recorded by

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
Fahim Kanani, Antonino Spinelli, Mordechai Shimonov, Husam Zbede, Nouha Hinnawi, Ron Lavy, Oded Zmora, Moshe Kamar
Journal of Clinical Medicine.2026; 15(4): 1448. CrossRef

Cite this Article

Cite this Article: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Efficacy and safety of novel alginate-based sealants (SEAL-G and SEAL-G MIST) in reducing anastomotic leakage following colorectal anastomosis: a prospective multicenter study

Ann Coloproctol. 2025;41(5):424-433. Published online October 23, 2025

DOI: https://doi.org/10.3393/ac.2025.00297.0042

XML Download

Figure

Efficacy and safety of novel alginate-based sealants (SEAL-G and SEAL-G MIST) in reducing anastomotic leakage following colorectal anastomosis: a prospective multicenter study

Fig. 1. CONSORT (Consolidated Standards of Reporting Trials) flowchart of the study. aAdvanced Medical Solutions.

Fig. 2. SEAL-G surgical sealant system (Advanced Medical Solutions) and delivery mechanism. The SEAL-G dual-syringe delivery system for intraoperative application of surgical hydrogel sealant is shown. The system utilizes 2 components: alginate with calcium carbonate (cross-linker) and alginate with acetate (trigger), which mix upon activation via a CO2 (Luer) propellant to rapidly form a hydrogel. Two delivery tips are available: an atraumatic mixer tip for precise application and a block-resistant spray tip for broader coverage. Cannulae are available in both 20 cm and 40 cm lengths. The system delivers 4 mL of sealant with a 60-second curing time and a 1-hour working window. Reprinted with permission from Advanced Medical Solutions [32].

Fig. 3. Comprehensive anastomotic leak (AL) rates from 4 major colorectal surgery studies. Reoperation rate is low in the SEAL-G Study compared to other studies. Together, these results reflect an evolving landscape of surgical techniques and postoperative care in colorectal surgery. DICA, Dutch Institute for Colorectal Audit; iCral, Italian ColoRectal Anastomotic Leakage.

Fig. 1.

Fig. 2.

Fig. 3.

Efficacy and safety of novel alginate-based sealants (SEAL-G and SEAL-G MIST) in reducing anastomotic leakage following colorectal anastomosis: a prospective multicenter study

Characteristic	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)	P-value^b
Age (yr)	68.5 (31.4–84.4)	70.3 (47.2–80.8)	68.5 (31.4–84.4)	0.338
Sex				0.338
Male	87 (54.4)	15 (45.5)	72 (56.7)
Female	73 (45.6)	18 (54.5)	55 (43.3)
Body mass index (kg/m²)	26.7 (17.9–43.3)	28.2 (19.6–37.4)	26.7 (17.9–41.0)	0.059
Tumor location				0.458
Right colon	96 (60.0)	20 (60.6)	76 (59.8)
Left colon	27 (16.9)	8 (24.2)	19 (15.0)
Sigmoid	36 (22.5)	5 (15.2)	31 (24.4)
Upper rectum	1 (0.6)	0 (0)	1 (0.8)
Tumor stage				0.400
I	17 (10.6)	4 (12.1)	13 (10.2)
II	51 (31.9)	7 (21.2)	44 (34.6)
III	70 (43.8)	19 (57.6)	51 (40.2)
IV	7 (4.4)	1 (3.0)	6 (4.7)
Unknown	15 (9.4)	2 (6.1)	13 (10.2)
ASA physical status				0.589
I	10 (6.3)	3 (9.1)	7 (5.5)
II	103 (64.4)	19 (57.6)	84 (66.1)
III	47 (29.4)	11 (33.3)	36 (28.3)

Characteristic	No. of patients (%)
Characteristic	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)
Procedure type
Right hemicolectomy	95 (59.4)	21 (63.6)	74 (58.3)
Left colectomy	24 (15.0)	5 (15.2)	19 (15.0)
Sigmoidectomy	25 (15.6)	4 (12.1)	21 (16.5)
Anterior resection	12 (7.5)	3 (9.1)	9 (7.1)
Subtotal colectomy	4 (2.5)	0 (0)	4 (3.1)
Surgical approach
Open	11 (6.9)	11 (33.3)	0 (0)
Laparoscopic/robotic	149 (93.1)	22 (66.7)	127 (100)
Anastomotic technique
Extracorporeal	22 (13.8)	20 (60.6)	2 (1.6)
Intracorporeal	127 (79.4)	2 (6.1)	125 (98.4)
Open	11 (6.9)	11 (33.3)	0 (0)
Sealant application
Complete circumferential coverage	149 (93.1)	31 (93.9)	118 (92.9)
Partial coverage	11 (6.9)	2 (6.1)	9 (7.1)

Outcome	Total (n=160)	SEAL-G^a group (n=33)	SEAL-G MIST^a group (n=127)	P-value^b
Anastomotic leak				0.280
Overall	5 (3.1)	2 (6.1)	3 (2.4)
Grade A/B	4 (2.5)	1 (3.0)	3 (2.4)
Grade C	1 (0.6)	1 (3.0)	0 (0)
Length of hospital stay (day)	5.8±3.7	8.4±5.5	5.1±2.8	<0.001
Time to leak diagnosis (day)	6.0±2.3	4.5±1.8	7.0±2.7	-
Reoperation^c	1 (0.6)	1 (3.0)	0 (0)	-
30-day Readmission	0 (0)	0 (0)	0 (0)	-
30-day Mortality	0 (0)	0 (0)	0 (0)	-

Study	Country	Reoperation (%)	Management without reoperation (%)	Total AL rate (%)
ANACO Study Group [34]	Spain	8.7	1.9	10.6
DICA [33]	The Netherlands	6.9	2.0	8.9
iCral Study Group [32]	Italy	4.8	1.6	6.4
This study	-	0.6	2.5	3.1

Table 1. Patient demographics and baseline characteristics

Values are presented as median (interquartile range) or number (%).

ASA, American Society of Anesthesiologists.

Advanced Medical Solutions.

P-values for comparison between SEAL-G and SEAL-G MIST groups, calculated using t-test for continuous variables and the chi-square or Fisher exact test for categorical variables as appropriate.

Table 2. Surgical characteristics and procedures

Advanced Medical Solutions.

Table 3. Clinical outcomes

Values are presented as number (%), mean±standard deviation, or number only. Tumor stages are reported according to pathological staging (pTNM) following surgical resection.

Advanced Medical Solutions.

P-values for comparison between SEAL-G and SEAL-G MIST groups; calculated using t-test for continuous variables and the chi-square or Fisher exact test for categorical variables as appropriate.

^cOnly 1 patient in the Seal-G group had a grade C leak requiring reoperation.

Table 4. Comparison of AL between this study and national colonic studies

AL, anastomotic leak; DICA, Dutch Institute for Colorectal Audit; iCral, Italian ColoRectal Anastomotic Leakage.