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Background: 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., Materials and Methods: 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., Results: 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., Conclusions: 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.

Background: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (© 2016 Wiley Periodicals, Inc.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare mechanical strength and rheology of existing tissue adhesives in a clinically relevant test setup with regard to colorectal anastomosis., Background: Little is known on the mechanical strength of tissue adhesives directly after application. Furthermore, rheological profiling may be important in understanding mechanical performance and explaining differences between adhesives. This study provides new data on the mechanical strength and rheology of a comprehensive list of tissue adhesives with regard to colorectal adhesiveness., Methods: Twelve surgical tissue adhesives were included: 4 cyanoacrylate adhesives (CA), 2 fibrin glues (FG), 3 polyethylene glycol (PEG) adhesives, and 3 albumin-based (AB) adhesives. Tubular rat colonic segments were glued together. Tensile (T), shear (S), and peel (P) strength were measured. Shear storage (G') and shear loss (G″) moduli were also evaluated., Results: CA adhesives were stronger than AB (T: P = 0.017; S: P = 0.064; P: P < 0.001), which, in turn, were stronger than PEG (T: P < 0.001; S: P < 0.001; P: P = 0.018). PEG were stronger than FG for shear (P = 0.013) and comparable for tensile and peel strength (P > 0.05). Within-group variation was smallest for CA. Mechanical strength correlated strongly between performed tests. Rheological properties (G' and G″) correlated strongly with mechanical strength for all adhesives combined., Conclusions: CA adhesives are the strongest and most homogenous group in terms of mechanical strength. Hydrogels (FG, AB) are heterogeneous, with lower mechanical strength than CA. FG are mechanically the weakest adhesives. Rheological profiles correlate to mechanical strength and may be useful for predicting mechanical performance.

Background: 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., Study Design: 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., Results: 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)., Conclusions: 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.

Background: Although cyanoacrylate glue (CA) has been widely used in various kinds of medical applications, its application in gastrointestinal anastomosis remains limited, and outcomes of experimental studies have not been satisfactory. This systematic review summarizes research regarding CA application in intestinal and colorectal anastomosis, and correlates methodological aspects to experimental outcomes., Methods: A systematic literature search was performed using Medline, Embase, Cochrane, and Web-of-Science libraries. Articles were selected if CA was applied to intestinal or colorectal anastomoses. Included articles were categorized according to CA molecular structure; the method details in each study were extracted and analyzed., Results: Twenty-two articles were included. More than half of the inclusions reported positive outcomes (seven articles) or neutral outcomes (eight articles). Analysis of the methods revealed that methodological details such as CA dosage, time of polymerization were not consistently reported. Porcine studies, inverted anastomosis, and n-butyl-cyanoacrylate studies showed more positive outcomes; everted anastomosis, and oversized sutures might negatively influence the outcomes., Conclusions: Owing to the positive outcome from the porcine studies, application of CA in gastrointestinal (GI) anastomosis still seems promising. To achieve a better consistency, more methodological details need to be provided in future studies. Optimizing the dosage of CA, choice of animal model, inverted anastomosis construction, and other method details may improve intestinal and colorectal anastomoses with CA application in future studies., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: In colorectal surgery, anastomotic leakage (AL) is the most significant complication. Sealants applied around the colon anastomosis may help prevent AL by giving the anastomosis time to heal by mechanically supporting the anastomosis and preventing bacteria leaking into the peritoneal cavity. The aim of this study is to compare commercially available sealants on their efficacy of preventing leakage in a validated mouse model for AL., Methods: Six sealants (Evicel, Omnex, VascuSeal, PleuraSeal, BioGlue, and Colle Chirurgicale Cardial) were applied around an anastomosis constructed with five interrupted sutures in mice, and compared with a control group without sealant. Outcome measures were AL, anastomotic bursting pressure, and death., Results: In the control group there was a 40% death rate with a 50% rate of AL. None of the sealants were able to diminish the rate of AL. Furthermore, use of the majority of sealants resulted in failure to thrive, increased rates of ileus, and higher mortality rates., Conclusions: If sealing of a colorectal anastomosis could achieve a reduction of incidence of clinical AL, this would be a promising tool for prevention of leakage in colorectal surgery. In this study, we found no evidence that sealants reduce leakage rates in a mouse model for AL. However, the negative results of this study make us emphasize the need of systemic research, investigating histologic tissue reaction of the bowel to different sealants, the capacity of sealants to form a watertight barrier, their time of degradation, and finally their results in large animal models for AL., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Abstract: Background: Anastomotic leakage in gastrointestinal (GI) surgery remains a major problem. Although numerous studies have been undertaken on the role of tissue adhesives as GI anastomotic sealants, no clear overview has been presented. This systematic review aims to provide a clear overview of recent experimental and clinical research on the sealing of different levels of GI anastomosis with tissue adhesives. Methods: We searched MEDLINE and Embase databases for clinical and experimental articles published after 2000. We included articles only if these addressed a tissue adhesive applied around a GI anastomosis to prevent anastomotic leakage or decrease leakage-related complications. We categorized results according to level of anastomosis, category of tissue adhesive, and level of evidence. Results: We included 48 studies: three on esophageal anastomosis, 13 on gastric anastomosis, four on pancreatic anastomosis, eight on small intestinal anastomosis, and 20 on colorectal anastomosis; 15 of the studies were on humans. Conclusions: Research on ileal and gastric/bariatric anastomosis reveals promising results for fibrin glue sealing for specific clinical indications. Sealing of pancreatico-enteric anastomosis does not seem to be useful for high-risk patients; however, research in this field is limited. Ileal anastomotic sealing was promising in every included study, and calls for clinical evaluation. For colorectal anastomoses, sealing with fibrin glue sealing seems to have more positive results than with cyanoacrylate. Further research should concentrate on the clinical evaluation of promising experimental results as well as on new types of tissue adhesives. This research field would benefit from a systematic experimental approach with comparable methodology. [Copyright &y& Elsevier]