Pancreatic Ductal Adenocarcinoma: The Characteristics of Contrast-Enhanced Ultrasound Are Correlated with the Hypoxic Microenvironment

A hypoxic microenvironment is associated with an increased risk of metastasis, treatment resistance and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify contrast-enhanced ultrasound (CEUS) characteristics that could predict the hypoxic microenvironment of PDAC. A total of 102 patients with surgically resected PDAC who underwent CEUS were included. CEUS qualitative and quantitative characteristics were analyzed. The expression of hypoxia-inducible factor-1 alpha (HIF-1) and glucose transporter-1 (GLUT1) were demonstrated by immunohistochemistry. The associations between CEUS characteristics and the HIF-1 alpha and GLUT1 expression of PDACs were evaluated. We found that HIF-1 alpha-high PDACs and GLUT1-high PDACs had a larger tumor size and were more prone to lymph node metastasis. There was a significant positive linear correlation between the expression of HIF-1 alpha and GLUT1. CEUS qualitative characteristics including completeness of enhancement and peak enhancement degree (PED) were related to the expression of HIF-1 alpha and GLUT1. A logistic regression analysis showed that tumor size, lymph node metastasis, incomplete enhancement and iso-enhancement of PED were independent predictors for HIF-1 alpha-high PDACs and GLUT1-high PDACs. As for quantitative characteristics, HIF-1 alpha-high PDACs and GLUT1-high PDACs showed higher peak enhancement (PE) and wash-in rate (WIR). CEUS can effectively reflect the hypoxia microenvironment of PDAC, which may become a noninvasive imaging biomarker for prognosis prediction and individualized treatment.