Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery

Abstract

Background The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following resection. Methods PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: “colorectal cancer recurrence,” “microbiome,” “anastomotic leak,” “anastomotic failure” and “mechanical bowel preparation”. Results There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery, and the physiological stress of the operation itself. Conclusion Interrogating the intestinal microbiome using next-generation sequencing technology has the potential to influence cancer outcomes following colonic resection.

Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model

“…First, Enterococcus faecalis and Pseudomonas aeruginosa were identified as two highly collagenolytic bacteria capable of causing leaks in both rats and mice. The discovery of E. faecalis as a leak pathogen is particularly important as it is the most common pathogen to be cultured from a leaking anastomosis in patients and the most difficult to eradicate from the intestinal tract. Although E. faecalis is classified as a low‐abundance commensal species among the normal microbiota, when properly provoked, it can bloom and behave as a virulent pathogen.…”

“…Because the gut is constantly exposed to a high burden of microbial organisms, healing may be dependent on a delicate balance between the health‐promoting microbiota and the virulence of pathobiota. Studies in animals as early as 1955 demonstrated a key role for the colonic microbiota in the pathogenesis of anastomotic healing. A more recent study examining anastomotic tissues in rodents showed a significant loss of health‐promoting taxa such as Ruminococcus , Bacteroidales family S24‐7 and Prevotellaceae , with a significant bloom in Escherichia and Enterococcus .…”

Long-term prognostic impact of surgical complications in the German Rectal Cancer Trial CAO/ARO/AIO-94

“…On the other hand, preoperative risk factors such as high levels of systemic inflammation or poor performance status have been identified as predictors of both the development of surgical complications and early disease recurrence in patients with colorectal cancer. Another factor recently considered to underlie the association between anastomotic leakage and colorectal cancer recurrence is alteration of the intestinal microbiome. Promotion of collagenase‐producing microbes by perioperative chemotherapy or radiotherapy and surgery may lead to impaired anastomotic healing, allowing shed luminal cancer cells to migrate and recolonize in extraintestinal sites.…”

Joint Modelling of Colorectal Cancer Recurrence and Death after resection using Multi-State Model with Cured Fraction

“…recurrence as the tumor has regrown to a detectable size (15). Patients who experience a recurrence are substantially at higher risk of mortality, and it is essential to find out who prognostic factors predispose a patient to recurrence (16)(17)(18)(19)(20). The time of occurrence of recurrence also influences the overall survival, such that worse survival is associated more with the early recurrence than the late one (21).…”