The role of the brush border enzyme intestinal alkaline phosphatase in patients undergoing duodenectomy

Background The brush border enzyme intestinal alkaline phosphatase(IAP) prevents endotoxemia through detoxification of lipopolysaccharides (LPS), regulates gut barrier function, and maintains microbial homeostasis. While IAP deficiency has been linked to pathologies such as diabetes, metabolic syndrome, ischemic heart disease, frailty, and a decreased life span, the supplementation of the naturally occurring enzyme has been proven to be beneficial in several studies. As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significant decrease in this important regulator of intestinal homeostasis.

Aim To test if PD leads to a reduction in IAP activity and a consecutive increase in LPS.

Methods Enzymehistochemistry was performed to investigate intestinal IAP distribution. Pre- and postoperative blood and stool samples were collected from patients undergoing PD. IAP levels were analyzed using the para-Nitrophenylphosphat method. Stool samples were normalized by BCA protein assay. The Limulus amebocyte assay was used to measure serum LPS levels.

Results In total, 45 patients undergoing PD and 23 controls undergoing other major abdominal surgery (MAS) without duodenectomy were included in the study. Enzymehistochemistry confirmed that IAP was mainly present in the duodenum. PD led to a significant decline in IAP levels compared to preoperative baseline levels (p< 0.0001). The decline in IAP levels clearly correlated with the length of proximal small intestinal resection (p=0.0034). Compared to control patients, PD caused a much more pronounced reduction in IAP levels (p<0.0001) – also after adjusting for surgical trauma in terms of operative time and blood loss. Simultaneously, PD caused a clearly more pronounced increase in serum LPS levels compared to other MAS (p=0.0001). Increased postoperative LPS levels were associated with an elongated length of hospital stay (p=0.0062).

Conclusion Based upon the functional roles for IAP, supplementation with exogenous IAP might improve the short- and long-term outcome of patients undergoing pancreaticoduodenectomy.

Publication History

Article published online:
19 August 2022