To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease recurrence. This was a nationwide cohort study of 9333 patients, prospectively registered in the database of the Danish Colorectal Cancer Group and merged with data from the Danish Pathology Registry and the National Patient Registry. Multivariable Cox regression analysis was used to adjust for confounding. The incidence of AL was 6.4%, 744 patients died within 120 days. Of the remaining 8589 patients, 861 (10.0%) developed local recurrence with no association to AL [adjusted hazard ratio (HR) = 0.78; 95% confidence interval (CI): 0.55-1.12; P = 0.184]. Distant recurrence developed in 1281 (14.9%) patients and more frequently after AL (adjusted HR = 1.42; 95% CI: 1.13-1.78; P = 0.003). AL was also associated with increased long-term mortality (adjusted HR = 1.20; 95% CI: 1.01-1.44; P = 0.042). In 2841 patients with stage III cancer, AL was associated with both decreased likelihood of receiving adjuvant chemotherapy (adjusted HR = 0.58; 95% CI: 0.45-0.74; P < 0.001) and a delay to initial administration (16 days; 95% CI: 12-20 days; P < 0.001). AL was significantly associated with increased rates of distant recurrence and long-term all-cause mortality. Cancelled or delayed administration of adjuvant chemotherapy may partly account for these findings.

The mortality associated with anastomotic leakage (AL) after colonic cancer surgery is high and management often results in permanent fecal diversion. Preservation of bowel continuity in combination with proximal loop diversion (salvage) may reduce the number of permanent ostomies without jeopardizing safety. This nationwide study used prospective data from the database of the Danish Colorectal Cancer Group, the National Patient Registry, and patient files. Patients with AL requiring surgery (grade C) were categorized according to the type of surgical treatment as anastomotic takedown with an end-ostomy or salvage. Thirty-day mortality, long-term mortality, and permanent ostomy rates were analyzed using multivariable logistic and Cox regression analyses. Anastomotic leakage occurred in 593 of 9,333 patients (6.4%), of whom 507 with grade C were included. Takedown and salvage were undertaken in 433 (85.4%) and 74 (14.6%) patients, respectively. Salvage was performed more frequently for Hinchey I-II or minor anastomotic defects and resulted in increased likelihood of stoma reversal (adjusted hazard ratio 3.24, 95% CI 2.04 to 5.16, p < 0.001), corresponding to a risk of permanent fecal diversion of 16.8%, compared with 54.5% after takedown. Adjusted mortality rates were comparable between the groups. A second episode of AL after stoma reversal occurred more frequently in patients with end-ileostomies (10 of 64) than in patients with end-colostomies (1 of 64) or loop-ileostomies (3 of 36), p = 0.017. Patients with Hinchey I-II and small anastomotic defect were safely managed by anastomotic salvage, which reduced the risk of permanent fecal diversion. Anastomotic salvage is a viable option for this subset of patients.

Background: Retrospective studies have drawn attention to possible detrimental effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the anastomotic leakage rate after colorectal resection. In this study, we examined the effects of the NSAID diclofenac on the breaking strength of an experimental colonic anastomosis and a skin incision as well as subcutaneous collagen accumulation. Methods: This was a randomized, blinded, placebo-controlled experimental study in 60 male Wistar rats treated with diclofenac 4 mg/kg/day or placebo. In each rat, a colonic anastomosis was performed and an expanded polytetrafluoroethylene (ePTFE) tube was placed subcutaneously. Incisional and anastomotic wound breaking strength and hydroxyproline content in the ePTFE tubes were measured 7 days after the operation. Results: We found no significant differences in any of the breaking strength measurements, but showed a median 38% reduction in hydroxyproline deposition as a result of diclofenac treatment (p = 0.03). In the placebo group, subcutaneous collagen deposition tended to correlate positively with skin incisional but negatively with anastomotic bio-mechanical strength. Conclusion: Postoperative diclofenac treatment significantly inhibited collagen deposition in subcutaneous granulation tissue. Anastomotic strength and skin wound strength were not significantly affected. The ePTFE model is suitable for assessing the effect of various drugs on collagen formation and thus on wound healing.