Anastomotic leakage (AL) is the most frequent life-threating complication following colorectal surgery. Several attempts have been made to prevent AL. This prospective, randomized, multicentre trial aimed to evaluate the safety and efficacy of nebulised modified cyanoacrylate in preventing AL after rectal surgery.

Patients submitted to colorectal surgery for carcinoma of the high-medium rectum across five high-volume centres between June 2021 and January 2023 entered the study and were randomized into group A (anastomotic reinforcement with cyanoacrylate) and group B (no reinforcement) and followed up for 30 days. Anastomotic reinforcement was performed via nebulisation of 1 mL of a modified cyanoacrylate glue. Preoperative features and intraoperative and postoperative results were recorded and compared. The study was registered at ClinicalTrials.gov (ID number NCT03941938).

Out of 152 patients, 133 (control group, n = 72; cyanoacrylate group, n = 61) completed the follow-up. ALs were detected in nine patients (12.5%) in the control group (four grade B and five grade C) and in four patients (6.6%), in the cyanoacrylate group (three grade B and one grade C); however, despite this trend, the differences were not statistically significant (p = 0.36). However, Clavien-Dindo complications grade > 2 were significantly higher in the control group (12.5% vs. 3.3%, p = 0.04). No adverse effects related to the glue application were reported.

The role of modified cyanoacrylate application in AL prevention remains unclear. However its use to seal colorectal anastomoses is safe and could help to reduce severe postoperative complications.

The aim of this review is to describe and assess the existing methods to cover colorectal anastomoses with biomaterials and their clinical impact in reducing anastomotic leakage (AL).

The most serious complication in colorectal surgery is AL. Despite improvements in its diagnosis and management, AL remains an unresolved issue. To prevent its appearance and clinical consequences, different external reinforcement techniques with synthetic or biomaterials have been described.

A systematic review search of the available literature until June 2022 was performed, looking for all literature regarding external reinforcement of colonic or colorectal anastomoses. After the review process, a classification of materials was proposed into solid and liquid materials, and an assessment of their clinical impact was performed. The study protocol has been registered at PROSPERO and has been reported in the line with PRISMA and AMSTAR Guidelines 11,12 .

Ninety-seven articles that fulfilled inclusion criteria, were identified and revised. Overall, 18 of the selected articles focused on human clinical trials and 79 on animal models. Only fibrin sealants, collagen patches, and omentoplasty have shown positive results in humans.

Fibrin sealants, collagen patches, and omentoplasty are, so far, the most studied biomaterials. However, further studies are required to confirm these findings before definite recommendations can be made.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery.

Resection and anastomosis of small intestine during colic can lead to adhesions and recurrent colic. Several methods are available to reduce the rate of adhesions in the postoperative period, such as the use of serosal barriers. Surgical glues form a smooth surface, are fast to apply, and could reduce surgery time when performing anastomosis. A recently developed UV-polymerizable methacrylate adhesive (UV-PMA) is designed to anchor into the biological tissues' top surface offering sealant and a smooth cover over the anastomosis site. This adhesive was used ex vivo on fifteen samples of equine jejunum as the second layer of a two-layer anastomosis (1L-UV-PMA group) and compared to a two-layer anastomosis (simple continuous pattern covered with a Cushing pattern; 2L-CT group), in terms of feasibility, bursting strength pressure (BSP), luminal diameter reduction (LDR), and time of construction. Data were analysed using a paired t-test or a chi²-test (P < 0.05). The results showed no statistical difference in BSP, LDR, or any mode of failure between the two anastomosis types. However, the glue anastomosis formed a tunnel-like anastomosis and shredded under pressure, before apparition of leakage, preventing its usage in clinical cases with this methodology. It was concluded that modification of the technique is warranted before testing in clinical cases. A preprint of a former version of the manuscript is available on researchsquare.com, which was not conducted to print and publication after peer reviewing. Since then, the manuscript has been modified to this current version.

The use of synthetic adhesives such as cyanoacrylates has been established previously for a wide range of clinical indications. However, more research is necessary to evaluate their use in digestive closures or anastomosis. New chemical formulations developed to achieve more flexibility of synthetic adhesives (i.e., based on n-butyl-2-cyanoacrylate) could be an alternative to achieve this purpose. The aim of this study was to investigate the feasibility of using flexible cyanoacrylate adhesives for large gastric incision closure in an animal model.

Twelve farm pigs were divided in two groups depending on the type of closure method applied. In all cases, extra-large seven centimeters gastrostomies were performed. Braided absorbable hand-sewn interrupted suture versus n-butyl-2-cyanoacrylate with softener closure were compared during a 3-week follow-up period. Histopathological aspects, hematologic and inflammatory biomarkers, and endoluminal pressure tolerated until leakage were assessed. The time spent on both closing procedures was compared.

No differences between the two groups were found in any of the histopathological and inflammatory variables evaluated. The glued group tolerated a significantly higher pressure than the manual suture group. A reduction of surgery time was also observed.

Our results suggest that flexible cyanoacrylates could be a feasible alternative to improve the clinical outcome of the closure of hollow viscera through more efficient sutureless procedures.

The optimal surgical approach to reconnecting bowel ends safely after resection is of great importance.

This project is focused on assessment of the perianastomotic microcirculation quality in the short postoperative period when using three different anastomosis techniques in experimental animal.

The experimental study involved 27 young female domestic pigs divided into three subgroups of 9 animals according to each surgical method of anastomosis construction in the sigmoid colon region: by manual suture, by stapler, or by gluing. Blood microcirculation in the anastomosis region was monitored using Laser Doppler Flowmetry (LDF). Anastomosis healing was evaluated by macroscopic and histological examination.

Evaluation of the microcirculation in the anastomosis region showed the smallest decrease in perfusion values in animals reconstructed by suturing (Δ= -38.01%). A significantly more profound drop was observed postoperatively after stapling or gluing (Δ= -52.42% and Δ= -59.53%, respectively). All performed anastomoses healed without any signs of tissue and function pathology.

Sewing, stapling, and gluing techniques for bowel anastomosis each have a different effect on regional microcirculation during 120 min. postoperatively. Nevertheless, the final results of anastomosis healing were found without of any pathology in all experimental animals managed by above mentioned anastomotic techniques.

Anastomotic leak after colorectal surgery is a significant cause of morbidity and mortality. The aim of this study was to evaluate the impact of a reinforced colo-colonic anastomosis with tissue adhesive, 2-octylcyanoacrylate (2-OCA), on the integrity of anastomotic healing as measured by anastomotic bursting pressure.

Sixty-eight female Sprague-Dawley rats underwent a rectosigmoid colon transection and a sutured end-to-end anastomosis followed by randomization to receive no further intervention or reinforcement with the tissue adhesive, 2-OCA. After seven postoperative days, a macroscopic assessment of the anastomosis, mechanical assessment to determine anastomotic bursting pressure, and a detailed semi-quantitative histopathologic healing assessment were performed.

Thirty-four animals were randomized to each group. Study characteristics did not differ between the groups. There was also no difference in the degree of adhesions present postoperatively. Although there was no difference between the net proximal and distal luminal areas in the two groups (0.37 cm²versus 0.55 cm², P = 0.26), the 2-OCA group exhibited evidence of stricture in 15% of anastomoses as compared with 3% in the suture-only group (P < 0.0001). Histologically, the presence of only fibroblasts density was statistically more evident in the 2-OCA group compared with the sutured-only anastomosis (P = 0.0183). There was not a significant increase in mechanical strength in the 2-OCA group (238.9 mm Hg) versus in the suture-only group (231.8 mm Hg). There was no difference in the rate of anastomotic leak in the 2-OCA as compared with the suture-only group (9.1 versus 8.8%).

Application of 2-OCA to reinforce a colo-colonic anastomosis clinically provides no benefit to its mechanical strength and detrimentally increases the rate of obstruction and/or stricture in this in vivo model.

Solution blow spinning is a technique for depositing polymer fibers with promising potential use as a surgical sealant. This study assessed the feasibility and efficacy of solution blow spun polymer (BSP) for sealing bowel perforations in a mouse model of partial cecal transection. We then evaluated its use for reinforcing a surgical anastomosis in a preclinical piglet model.

Three commercially available surgical sealants (fibrin glue, polyethylene glycol (PEG) hydrogel, and cyanoacrylate) were compared to BSP in the ability to seal partially transected cecum in mice. For anastomosis feasibility testing in a piglet model, piglets were subjected to small bowel transection with sutured anastomosis reinforced with BSP application. Outcome measures included anastomotic burst pressure, anastomotic leak rate, 14-day survival, and complication rate.

For the mouse model, the survival rates for the sealants were 30% for fibrin glue, 20% for PEG hydrogel, 78% for cyanoacrylate, and 67% for BSP. Three of 9 mice died after BSP administration because of perforation leak, failure to thrive with partial obstruction at the perforation site, and unknown causes. All other mice died of perforation leak. The mean burst pressure at 24h was significantly higher for BSP (81mm Hg) when compared to fibrin glue (6mm Hg, p=0.047) or PEG hydrogel (10mm Hg, p=0.047), and comparable to cyanoacrylate (64mm Hg, p=0.91). For piglets, 4 of 4 animals survived at 14days. Mean burst pressures at time of surgery were 37±5mm Hg for BSP and 11±9mm Hg for suture-only controls (p=0.09).

Solution blow spinning may be an effective technique as an adjunct for sealing of gastrointestinal anastomosis. Further preclinical testing is warranted to better understand BSP properties and alternative surgical applications.

Anastomotic leak in the gastrointestinal tract is one of the most important complications of resection. They are the main cause of reoperation, their occurrence worsens the prognosis of the patient, increasing the proportion of direct mortality, as well as being a significant risk factor for recurrence of cancer. The risk of leaks within the gastrointestinal tract is greatly varied, depending on the location and extent of the resection, but also on patient, disease or a surgical procedure, including surgeon. To determine the potential risk of leakage can be significant for introduction some prophylactic actions. Some of them have the character of general recommendations, as proper nutrition of the patient in the perioperative period, while another part is directly connected to the surgical procedure. The second group includes protective stoma, the use of tissue glues, insertion transrectal drain for rectal anastomosis decompression, the use of stents or the use of collagen matrix coated with fibrinogen and thrombin. Important to reduce the proportion of leaks can be more precise and targeted prophylactic recommendations, based on the individualized determination of risk factors leaks. Further research for this purpose are necessary for this purpose, the big hope can be associated with data obtained through mobile applications.

Tissue adhesives (TA) may be useful to strengthen colorectal anastomoses, thereby preventing anastomotic leakage (AL). Previous studies have identified cyanoacrylate (CA) TAs as the most promising colonic anastomotic sealants. This study investigates the protective effects of sealing colonic anastomoses with various CAs.

Fifty-five Wistar rats underwent laparotomy and transection of the proximal colon. An anastomosis was created with 4 interrupted sutures followed by either application of Histoacryl Flexible, Omnex, Glubran 2, or no TA seal. An additional control group was included with a 12-suture anastomosis and no TA seal. After 7 days, the rats were sacrificed and scored for the presence of AL as the main outcome. Secondary outcomes were the occurrence of bowel obstruction, adhesions, and anastomotic bursting pressure. Histological evaluation was performed.

The highest AL rate was found in the Glubran 2 group (7/11), followed by the 4-sutures group without TA (5/11), and the Omnex group (5/11). Histoacryl Flexible showed the lowest AL rate (2/11). In the control group, only one rat showed signs of AL. Histologically, the highest influx of inflammatory cells was found in the 4-suture group without TA and for Omnex and Glubran 2. Histoacryl Flexible caused more mature collagen deposition when compared to the other TA groups.

Histoacryl Flexible showed the lowest leakage rate compared to the other TA groups and to the 4-suture control group. Glubran 2 showed the highest AL rate and a high inflammatory response. Histoacryl Flexible was associated with the presence of more mature collagen and seems to promote anastomotic healing.

Colorectal anastomotic leakage (CAL) remains a major complication after colorectal surgery. Despite all efforts during the last decades, the incidence of CAL has not decreased. In this review, we summarize the available strategies regarding prevention, prediction and intervention of CAL and categorize them into three categories: communication, infection and healing disturbances. These three major factors actively interact during the onset of CAL. We aim to provide an integrated approach to CAL based on its etiology. The intraoperative air leak test, intraoperative endoscopy, radiological examinations and stoma construction mainly aim to detect and to prevent communication between the intra- and extra-luminal content. Other strategies including postoperative drainage, antibiotics, and infectious-parameter evaluation are intended to detect and prevent anastomotic or peritoneal infection. Most currently available interventions for CAL focus on the control of communication and infection, while strategies targeting the healing disturbances such as lifestyle changes, oxygen therapy and evaluation of metabolic biomarkers still lack wide clinical application. This simplified categorization may contribute to an integrated understanding of CAL. We strongly believe that this integrated approach should be taken into consideration during clinical practice. An integrated approach to CAL could contribute to a better understanding of the etiology of CAL and eventually better patient outcome.

Tissue adhesives (TAs) in gastrointestinal surgery are gradually gaining acceptance. Before implementation as colonic sealants, an evaluation of the sealing capability of a TA when in contact with fecal matter, as in a leaking anastomosis, is needed. In this study, we used clinically available TAs for the sutureless closure of colonic defects evaluating mechanical strength and tissue healing.

A total of 160 rats were divided into 8 groups. Two .5-cm incisions were created, one in the proximal and another in the distal colon. Incisions were sealed with a TA: Histoacryl Flex, Bioglue, Dermabond, Tissucol, Duraseal Xact, gelatin-resorcinol-formaldehyde or Glubran 2. A control group was included in which the colonic defects were not sealed. Follow-up time was 3 or 10 days. Clinical complication rate, bursting pressure, and histopathologic analysis was included.

Leakage rates in the TA groups were highest for Duraseal Xact, Bioglue, and gelatin-resorcinol-formaldehyde at 3 and 10 days. The cyanoacrylates Glubran 2, Histoacryl Flex, and Omnex, and the fibrin glue Tissucol showed the lowest overall clinical complication rates while maintaining the highest bursting pressure at day 10. Histoacryl Flex exhibited significantly higher collagen formation at day 10 than the other TAs.

This experimental model evaluates the protective effect of a TA seal on a leaking colonic defect. We found large differences in leakage rates and inertness of the tested TAs. The cyanoacrylates Histoacryl Flex, Omnex, and Glubran 2 as well as the fibrin glue Tissucol demonstrated the lowest leakage rates and the most inert histopathologic profile while maintaining high mechanical strength.

Tissue adhesives may be useful for sealing bowel anastomoses by preventing anastomotic leakage. Prior to clinical implementation, an in-depth analysis of the clinical and immunohistopathological effects of tissue adhesives on the target tissue and of the mechanical strength of the adhesive bond in an in vivo model is needed.

In 84 rats, two bowel segments were glued using one of the following tissue adhesive: Bioglue, Gelatin-resorcinol-formaldehyde (GRF), Glubran 2, Histoacryl Flex, Omnex, Duraseal Xact, or Tissucol. Rats were followed for 7 or 28 days. Endpoints were clinical complication rate, mechanical strength, and immunohistopathological reactions.

Of the seven tissue adhesives, GRF and Bioglue showed the highest rates of bowel wall destruction and ileus and the most severe immunohistopathological tissue reactions at 7 and 28 days. Cyanoacrylates (Histoacryl Flex, Omnex, Glubran 2) showed high mechanical strength and mild immunohistopathological reactions at 7 and 28 days. Duraseal Xact and Tissucol were the most inert tissue adhesives, but exhibited low mechanical strength. At 28 days, mechanical strength was significantly correlated to CD8, CD68, and Ki67 cell counts.

Based on the clinical and immunohistopathological outcomes, GRF and Bioglue were found to be the least suitable tissue adhesives for colonic use. Duraseal Xact and Tissucol were inert but also showed low mechanical strength. Cyanoacrylates exhibited mild clinical and immunohistopathological effects while maintaining high strength, which makes them promising as colonic sealants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 846-854, 2017.

Anastomotic leakage after gastrointestinal surgery remains a challenging clinical problem. This study aimed to investigate the effectiveness of TissuCol (fibrin glue), Histoacryl Flex (n-butyl-2-cyanoacrylate), and Duraseal (polyethylene glycol) on colorectal anastomotic healing during experimental colitis.

We first performed colectomy 7 days after 10 mg trinitrobenzene sulfonic acid (TNBS)-induced colitis to validate a rat TNBS-colitis-colectomy model. Subsequently, this TNBS-colitis-colectomy model was used in 73 Wistar rats that were stratified into a colitis group (CG, no adhesive), a TissuCol group (TG), a Histoacryl group (HG), and a Duraseal group (DG). Anastomotic sealant was applied with one adhesive after constructing an end-to-end hand-sewn anastomosis. Clinical manifestations, anastomotic bursting pressure, and immunohistochemistry of macrophage type-one (M1) and type-two (M2) was performed on postoperative day (POD)3 or POD7.

TNBS-caused mucosal and submucosal colon damage and compromised anastomotic healing (i.e., abscess formation and low anastomotic bursting pressure). On POD3, higher severity of abscesses was seen in CG. Average anastomotic bursting pressure was 53.2 ± 35.5 mm Hg in CG, which was significantly lower than HG (134.4 ± 27.5 mm Hg) and DG (95.1 ± 54.3 mm Hg) but not TG (83.4 ± 46.7 mm Hg). Furthermore, a significantly higher M2/M1 index was found in HG. On POD7, abscesses were only seen in CG (6/9) but not in other groups; HG had the lowest severity of adhesion.

We describe the first surgical IBD model by performing colectomy in rats with TNBS-induced colitis, which causes intra-abdominal abscess formation and compromises anastomotic healing. Anastomotic sealing with Histoacryl Flex prevents these complications in this model. Alternative activation of macrophages seems to be involved in its influence on anastomotic healing.

To investigate the effects of n-butyl-2-cyanoacrylate on tracheal anastomoses in terms of increased tension and intraluminal pressure ex vivo.

Ex vivo experimental study.

Tertiary referral center (Department of Otolaryngology).

Thirty sheep tracheas were used. Four cartilage rings were resected from the tracheas that were 20 cm in length. End-to-end anastomoses were performed by using Vicryl only (group 1), Vicryl and n-butyl-2-cyanoacrylate (group 2), and n-butyl-2-cyanoacrylate only (group 3). The amount of force to break off the anastomosis and the amount of intraluminal pressure to arouse air leakage through the anastomosis were measured.

The mean force required to break off was 171.9 ± 29.7 N in group 1, 164.8 ± 26 N in group 2, and 13.52 ± 2 N in group 3. The mean force required to break off in group 3 was significantly lower than those in groups 1 and 2 (P = .008 and P = .008, respectively). The mean pressure required to cause air leakage was 49.6 ± 9.1 mm Hg in group 1, 113 ± 14.4 mm Hg in group 2, and 15 ± 4.2 mm Hg in group 3. Group 2 was found to be more resistant to intraluminal pressure than groups 1 and 3 (P = .008 and P = .008, respectively).

n-Butyl-2-cyanoacrylate had no significant effect on tensile strength. However, its application on the suture line provided extra pressure resistance ex vivo. We believe that further studies need to be conducted to investigate its long-term effects and histological impact on tracheal anastomoses in vivo.

Colorectal anastomoses created in a contaminated environment result in a high leakage rate. This study investigated whether using anastomotic sealants (TissuCol(®), Histoacryl(®) Flex, and Duraseal(®)) prevents leakage in a rat peritonitis model.

Sixty-seven Wistar rats were divided into control and experimental groups (TissuCol, Histoacryl, and Duraseal groups). Peritonitis was induced 1 day before surgery with the cecal ligation puncture model. On day 0, colonic anastomosis was constructed with sutures and then sealed with no adhesive (control group) or one select adhesive (experimental groups). Bursting pressure, abscess formation, and adhesion severity were evaluated on day 3 or day 14. Hematoxylin and eosin staining and immunohistochemical staining for CD4, CD8, CD206, and iNOS were performed.

On day 3, bursting pressures of the TissuCol group (120.1 ± 25.3 mmHg), Histoacryl group (117.3 ± 20.2 mmHg), and Duraseal group (123.6 ± 35.4 mmHg) were significantly higher than the that of the control group (24.4 ± 31.7 mmHg, p < 0.001). Abscesses around the anastomosis were found in the control group (6/7) and Duraseal group (2/9) but not in the TissuCol group or Histoacryl group. A higher number of CD206+ cells (M2 macrophages), a lower number of iNOS+ cells (M1 macrophages), a higher M2/M1 index, and a higher CD4+/CD8+ index were seen at the anastomotic site in all experimental groups compared with the control group on day 3. On day 14, abscesses were only found in the control group. Adhesion severity in the Duraseal group was significantly lower than that in the control group (p = 0.001).

Anastomotic sealing using TissuCol(®), Histoacryl(®) Flex, or Duraseal(®) seems to be an effective and safe option to prevent leakage in contaminated colorectal surgery. The presence of large numbers of anti-inflammatory macrophages seems to be involved in preventing the leakage.