Microvascular Endothelium in Patients with Pancreatic Head Cancer and Relationship with Surgical Outcomes

BACKGROUND: The proportion of pancreatic cancer remains high in the overall cancer incidence. Pancreatic ductal adenocarcinoma is a highly aggressive and lethal tumor. AIM: To evaluate the microvascular endothelial function in patients undergoing pancreatic head cancer surgery and to establish a correlation with surgical outcomes. MATERIALS AND METHODS: A prospective observational randomized study was conducted from 2009 to 2022. The study included two cohorts: healthy subjects (control group, n=٤٠) and patients diagnosed with pancreatic head cancer (patient group, n=95) who underwent a Whipple procedure. The assessment of the functional parameters of the microvascular endothelium included measurements of circulating endothelial cell count, von Willebrand factor (vWF), and endothelium-dependent vasodilation. The patient group was divided into two subgroups: the main subgroup included patients who underwent a laparoscopic Whipple procedure (n=44) and the comparison subgroup consisted of those who underwent laparotomy (n=51). In the main subgroup, patients were administered a combination of arginine glutamate (1.0 g daily) and enalapril (2.5–5.0 mg daily) for the treatment of endothelial dysfunction. RESULTS: In the main group, sums of circulating endothelial cell and vWF were significantly lower (7.0±1.4 and 93.6±23.3, respectively), whereas endothelium-dependent vasodilation was higher (9.8±3.2) as compared to the control group (p 0.0001). In the population of the main subgroup who received endothelial dysfunction treatment, a 4.2- and 4.6-fold reduction in circulating endothelial cell and vWF levels, respectively, was observed (p 0.0001 for both). Additionally, a 4.0-fold increase in endothelium-dependent vasodilation was documented (p 0.0001). The circulating endothelial cell count of more than 7.0×104 cells/L, vWF of more than 120%, and less than 10% increase in endothelium-dependent vasodilation during the study period increase the risk of early postoperative complications by 2.7, 1.9, and 1.7 times, respectively (p 0.0001). The incidence of surgical and non-surgical complications was 28.4 and 24.2%, respectively. The in-hospital mortality rate was 5.3%. In the main subgroup, the incidence of septic and non-surgical complications was 2.5 and 3.1 times lower, respectively, than in the comparison subgroup (p 0.05). CONCLUSIONS: The combination of endothelial dysfunction treatment and laparoscopic surgical technique has been shown to have a protective effect on the microvascular endothelium in patients with pancreatic head cancer, reducing the risk of early postoperative complications. The baseline vascular endothelial function has been demonstrated to correlate with the risk of early postoperative complications and long-term adverse events, including relapses and/or metastases.