An Integrated Approach to Colorectal Anastomotic Leakage

__Abstract__ Colorectal anastomotic leakage (CAL) still remains a frequent and most dangerous complication after gastrointestinal surgery, occurring in 4-33% patients and contributing to one third of postoperative mortality. CAL substantially prolongs hospital stay ? by one to two weeks - and greatly increases medical costs by as much as $24,000 within the first period of hospitalization, thereby approximately tripling the expenditure relative to that of patients without CAL. Due to the high risk of postoperative mortality, substantial efforts have been made to investigate means of preventing and detecting CAL. In recent decades, however, even with substantial improvements in surgical technique, no clear decrease in CAL rate has been achieved. Much effort has been devoted to selecting patients with higher risks of CAL, and many risk factors have been identified, such as being male, smoking, alcohol abuse, obesity, a high American Society of Anesthesiologists (ASA) score, low level (e.g. rectal) anastomosis, tumor stage, urgent operation, increased blood loss, and prolonged duration of surgery have been revealed. Previous studies by our research group also reported several novel risk factors including after-hours surgery, and long-term and preoperative administration of corticosteroids. However, these risk factors seem to cover most patients and thus may have limited value in the preoperative selection of patients

Cytokines as early markers of colorectal anastomotic leakage: A systematic review and meta-analysis

Purpose. Colorectal anastomotic leakage (CAL) is one of the most severe complications after colorectal surgery. This meta-analysis evaluates whether systemic or peritoneal inflammatory cytokines may contribute to early detection of CAL. Methods. Systematic literature search was performed in the acknowledged medical databases according to the PRISMA guidelines to identify studies evaluating systemic and peritoneal levels of TNF, IL-1β, IL-6, and IL-10 for early detection of CAL. Means and standard deviations of systemic and peritoneal cytokine levels were extracted, respectively, for patients with and without CAL. The meta-analysis of the mean differences was carried out for each postoperative day using Review Manager. Results. Seven articles were included. The meta-analysis was performed with 5 articles evaluating peritoneal cytokine levels. Peritoneal levels of IL-6 were significantly higher in patients with CAL compare

Hyperbaric oxygen therapy improves colorectal anastomotic healing

Purpose: Hyperbaric oxygen treatment (HBOT) has been found to improve the healing of poorly oxygenated tissues. This study aimed to investigate the influence of HBOT on the healing in ischemic colorectal anastomosis. Methods: Forty Wistar rats were randomly divided into a treatment group that received HBOT for 10 consecutive days (7 days before and 3 days after surgery), or in a control group, which did not receive the therapy. Colectomy with an ischemic anastomosis was performed in all rats. In each group, the rats were followed for 3 or 7 days after surgery to determine the influence of HBOT on anastomotic healing. Results: Five rats from each group died during follow-up. No anastomotic dehiscence was seen in the HBOT group, compared to 37.5 % and 28.6 % dehiscence in the control group on postoperative day (POD) 3 and 7, respectively. The HBOT group had a significantly higher bursting pressure (130.9 ± 17.0 mmHg) than the control group (88.4 ± 46.7 mmHg; p = 0.03) on POD 3. On POD 3 and POD 7, the adhesion severity was significantly higher in the control groups than in the HBOT groups (p < 0.005). Kidney function (creatinine level) of the HBOT group was significantly better than of the control group on POD 7 (p = 0.001). Interestingly, a significantly higher number of CD206+ cells (marker for type 2 macrophages) was observed in the HBOT group at the anastomotic area on POD 3. Conclusion: Hyperbaric oxygen enhanced the healing of ischemic anastomoses in rats and improved the postoperative kidney function

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 stud

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection

Aim: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. Method: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1β), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. Results: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0–14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). Conclusion: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool

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

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