Impact of tissue adhesives on the prevention of anastomotic leakage of colonic anastomoses: an in vivo study.

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.

The prevention of colorectal anastomotic leakage with tissue adhesives in a contaminated environment is associated with the presence of anti-inflammatory macrophages.

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.

Prevention of leakage by sealing colon anastomosis: experimental study in a mouse model.

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.

Tissue adhesives in gastrointestinal anastomosis: a systematic review.

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.

Carpal Collapse After Scaphoid Nonunion: A Novel Combined Approach to the 1,2 Intercompartmental Supraretinacular Artery Radial Flap.

Purpose: Scaphoid nonunion remains a major problem in hand surgery. The 1,2 intercompartmental supraretinacular artery flap (1,2 ICSRA), as first described by Zaidemberg et al, is widely used with reported union rates of approximately 80%. However, its use is limited in the case of associated carpal collapse as in dorsal intercalated segmental instability (DISI) and humpback deformity. In this study, we present a novel approach to this flap enabling the correction of associated carpal collapse. Methods: Between 2006 and 2015, 9 patients with scaphoid nonunion or delayed union with carpal collapse were treated with a vascularized bone flap based on the 1,2 ICSRA using a combined volar and dorsal approach. Immobilization in a short-arm cast was applied for 8 weeks. Union rates, correction of DISI and humpback deformity, as well as clinical end points were noted. In addition, scapholunate (SL) angles were measured using 2 accepted radiological techniques, employing either the scaphoid midline axis or its proximal radiological landmarks as a reference. Results: All cases united and a median time to bone consolidation of 4 months (range, 2-5 months) was observed. Preoperative DISI deformities (n = 4) were corrected in all patients. Humpback deformities (n = 5) were also corrected. Two patients had repeat surgery: one for K-wire removal after bony consolidation and the other for neuropathic pain. Conclusions: The 1,2 ICSRA bone flap is a reliable treatment for scaphoid nonunion associated with carpal collapse. This combined volar and dorsal approach permits the correction of DISI and humpback deformity without compromising the scaphoid vascular supply, which eliminates the need to use free bone flaps from other sites. In this series, we observed a 100% union rate. Two patients required reoperation for symptomatic hardware and dorsal wrist pain linked to superficial neuritis. Type of study/level of evidence: Therapeutic IV.

Clinical, mechanical, and immunohistopathological effects of tissue adhesives on the colon: An in-vivo study.

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.

Sutureless closure of colonic defects with tissue adhesives: an in vivo study in the rat.

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.

Watchful waiting in incisional hernia: is it safe?

BACKGROUND: Incisional hernia (IH) is among the most common postoperative complications after abdominal surgery. Operative treatment (OT) using mesh is the treatment of choice. A strategy of watchful waiting (WW) might be a considered in some patients. This retrospective study compares the outcomes of WW and OT. METHODS: All patients presenting with IH in an academic surgery department between January 2004 and December 2009 were analyzed according to whether they were treated by WW or OT. Crossovers between both groups were also analyzed. Patient characteristics, information about the initial abdominal operative procedure, symptoms at presentation, and characteristics of the hernia were collected retrospectively. In case of OT, postoperative complications were analyzed. RESULT: In total, 255 patients were included; 151 (59%) in the OT group and 104 (41%) in WW group. The median follow-up was 68 months (interquartile range [IQR], 52-93). The reasons for WW were the absence of symptoms in 34 patients (33%), comorbidities in 24 (23%), and obesity in 23 (22%). During follow-up, 34 patients (33%) crossed over from WW to OT. Eight of the crossovers (24%) were emergency repairs owing to incarceration at a median of 1 month (IQR, 1-5) after the start of WW. The incidence of unexpected intraoperative intestinal perforation was greater in the crossover group (13%) compared with the OT group (2%; P = .002). Postoperative fistulas were seen in 7% of patients who crossed over from WW to OT versus 0% in primary OT (P = .002). Postoperatively, 3 patients died, 2 of whom were treated operatively after belonging initially to the WW group. CONCLUSION: WW for IH leads to high crossover rates with significantly greater incidence of intraoperative perforations, fistulas, and mortality, than in the OT group, particularly in patients who require emergency repair of IH owing to incarceration.

Critical analysis of cyanoacrylate in intestinal and colorectal anastomosis.

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.

Colorectal anastomotic leakage caused by insufficient suturing after partial colectomy: a new experimental model.

BACKGROUND: Colorectal anastomotic leakage (CAL) is the most important complication of colorectal surgery, accounting for one third of post-operative deaths. To prevent it, many interventions have been tested in animal models, mostly rats. However, few of these models have been validated. We aimed to develop a reproducible rat CAL model by creating an anastomosis with insufficient suturing after partial colectomy. METHODS: To establish the number of sutures that would create an appropriate leakage rate for research (20%-50%), partial colectomy was performed in 60 Wistar rats using a 12-suture anastomosis in the control group and an anastomosis with insufficient suturing in the experimental group, starting with five sutures. Seven days later, the rats were examined for the occurrence and severity of CAL, the presence of adhesions, and anastomotic bursting pressure. When an acceptable leakage rate was achieved, the experimental and control studies were repeated twice to confirm the adequacy of the chosen technique. RESULTS: On day 7, five-suture and 12-suture anastomoses had leakage rates of 50% vs. 30%, 44.4% vs. 20%, and 50% vs. 20%, respectively, in the various series. Overall, the five-suture group had a significantly higher CAL rate than did the 12-suture group (48.3% vs. 23.3%; p=0.045). It also had higher CAL severity and more adhesions (p for both<0.05). The bursting pressure of these anastomoses was significantly lower than that in the 12-suture group (116.8±58.9 mm Hg vs. 150.4±50.3 mm Hg; p=0.041). CONCLUSION: Anastomosis with five sutures after partial colectomy provides a suitable rat CAL model. Its future applications may help to improve the consistency of CAL studies.