New insights into anastomotic leakage after rectal cancer resection

Anastomotic leakage (AL) is a severe complication after rectal cancer surgery, occurring in 20-25% of cases, resulting in increased morbidity, mortality, extended recovery periods, additional interventions, and significant economic burdens. This dissertation provides new insights into the etiology, long-term outcomes, and economic impacts of AL, presenting innovative strategies for prevention and treatment.
The first part investigates the gut microbiome's influence on anastomotic healing. Microbial dysbiosis, characterized by decreased diversity and increased facultative anaerobes like Enterococcus, negatively impacts recovery. Tranexamic acid, an inhibitor of plasminogen activation, effectively reduces collagen breakdown and AL incidence in mouse models without disturbing microbial balance. Additionally, brief dietary prehabilitation using a high-fiber diet enhances microbial diversity and reduces AL rates. Clinical translation through perioperative microbiome analyses within the IMARI study revealed significant microbial shifts postoperatively, including Enterococcus dominance and reduced alpha diversity, providing valuable insights into human perioperative microbiome dynamics.
The second part assesses the long-term clinical outcomes of AL. The STOMA-score enables clinicians to better predict stoma risk one year post-leakage based on patient and leakage characteristics. Additionally, various AL treatment strategies are compared, emphasizing reactivation leakages after stoma reversal, an underestimated issue significantly affecting quality of life and surgical complexity.
The third part addresses the financial implications of AL. Cost analyses reveal substantial variation internationally and methodologically. The IMARI study evaluates treatment strategy costs in the first postoperative year and another study highlights that persistent leakages significantly amplify financial burdens, emphasizing the need for preventive, cost-effective interventions.