Colorectal anastomotic healing: why the biological processes that lead to anastomotic leakage should be revealed prior to conducting intervention studies

Abstract

BackgroundAnastomotic leakage (AL) remains the most dreaded complication after colorectal surgery and causes high morbidity and mortality. The pathophysiology of AL remains unclear, despite numerous studies that have been conducted on animals and humans, probably due to the undetermined healing process of colorectal anastomoses. Increasing basic knowledge on this healing process may shed more light on causal factors of AL, and additionally reduce the quantity and accelerate the quality of experimental studies. In this debate article, our aim was to provide different perspectives on what is known about the colorectal healing process in relation to wound healing and AL.DiscussionSince knowledge on anastomotic healing is lacking, it remains difficult to conclude which factors are essential in preventing AL. This is essential information in the framework of humane animal research, where the focus should lie on Replacement, Reduction and Refinement (3Rs). While many researchers compare anastomotic healing with wound healing in the skin, there are substantial recognized differences, e.g. other collagen subtypes and different components involved.SummaryBased on our findings in literature as well as discussions with experts, we advocate stop considering anastomotic healing in the gastrointestinal tract and cutaneous healing as a similar process. Furthermore, intervention studies should at least address the anastomotic healing process in terms of histology and certain surrogate markers. Finally, the anastomotic healing process ought to be further elucidated – with modern techniques to achieve 3Rs in animal research - to provide starting points for potential interventions that can prevent AL.

Impaired collagen synthesis in the rectum may be a molecular target in anastomotic leakage prophylaxis

“…AL also occurs in patients without these risk factors. This result indicates the involvement of endogenous factors in the pathogenesis of AL . Furthermore, there are no specific pharmaceuticals for AL prophylaxis .…”

“…Furthermore, there are no specific pharmaceuticals for AL prophylaxis . Therefore, elucidating the pathogenesis could lead to novel therapeutic targets for AL prevention …”

Intra-Operative Anastomotic Leak Rates and Testing Methodology in Colorectal Resection Surgery

“…Although some risk factors for anastomotic leak including male gender, steroid use, obesity, malnutrition, and intraoperative blood loss are known, other yet unidentified risk factors certainly exist [9,35]. It is possible that the subpopulation of patients with an initially positive leak test who develop a post-operative leak includes patients at higher risk for anastomotic leak, potentially due to comorbidity, changes in the composition of the patient's microbiome, decreased gastrointestinal healing, or increased damage to colorectal tissue [36,37]. Our finding that the rate of post-operative anastomotic leak is increased in the population of patients with an initially positive intra-operative leak test, despite intra-operative repair, is consistent with previous reports, and suggests that additional strategies for intraoperative leak repair may be needed for this high risk population [31].…”

No Coil® Placement in Patients Undergoing Left Hemicolectomy and Lower Anterior Resection for Colorectal Cancer: Efficacy, Tolerability and Differences.

“…Nevertheless, this surgical step remains a critical point in terms of tolerability and post-operative complications. Anastomotic leak (AL), de ned as a defect of the intestinal wall occurring in the anastomotic site that leads to a communication between the intra-and extraluminal compartments [7] is the most important complication of colorectal surgery [8]. There is no consensus about the prevalence of AL, since it varies according to the site of anastomosis, with colocolonic leak frequency being up to 0-9%, and colorectal and coloanal leak rising to 20% [7][8][9].…”