Anastomotic leak in colorectal cancer patients: New insights and perspectives.

Anastomotic leak (AL) remains a potentially life-threatening sequela of colorectal surgery impacting on mortality, short- and long-term morbidity, quality of life, local recurrence (LR) and disease-free survival. Despite technical improvements and the identification of several surgery- and patient-related factors associated to the risk of AL, its incidence has not significantly changed over time. In this context, the clarification of the mechanisms underlying anastomotic healing remains an important unmet need, crucial for improving patients' outcomes. This review concentrates on novel key findings in the etiopathogenesis of AL, how they can contribute in determining LR, and measures which may contribute to reducing its incidence. AL results from a complex, dynamic interplay of several factors and biological processes, including host genetics, gut microbiome, inflammation and the immune system. Many of these factors seem to act in concert to drive both AL and LR, even if the exact mechanisms remain to be elucidated. The next generation sequencing technology, including the microbial metagenomics, could lead to tailored bowel preparations targeting only those pathogens that can cause AL. Significant progress is being made in each of the reviewed areas, moving toward translational and targeted therapeutic strategies to prevent the difficult complication of AL.