Abstract
PurposeThe heat-sink effect is one reason for the insufficient temperature increase in hyperthermia (HT) treatment for cancer. Microbubbles (MBs) nucleate inertial cavitation under therapeutic ultrasound (TUS) exposure, which form microbubble-enhanced ultrasound (MEUS), which results in blocking blood perfusion in the targeted liver tissues. This study aimed to determine if synergistic effects exist during HT in the liver when combined with MEUS.MethodsForty rabbits with surgically exposed livers were randomly divided into TUS + MB + HT, MB + HT, normal saline + HT, and MB + sham groups (n = 10 in each group). Liver perfusion was evaluated using contrast-enhanced ultrasound. The temperatures of the liver tissues were monitored using thermocouples. Pathological changes were determined by hematoxylin and eosin (H&E) staining. Serum hepatic transaminases were evaluated.ResultsMEUS pretreatment almost completely blocked the perfusion of targeted areas. The TUS + MB + HT and MB + HT groups showed significantly higher temperatures in treated areas than those in the other groups. However, the TUS + MB + HT group exhibited a more stable and regular increase in temperatures in the fitting curves compared with the MB + HT group. H&E staining revealed swelling hepatocytes, hemorrhage, and thrombosis in the portal area in the TUS + MB + HT group.ConclusionMEUS reduced the blood perfusion in the targeted liver tissues, and, therefore, overcame the heat-sink effect during the HT procedure in rabbits. MEUS pretreatment might have the potential to enhance the therapeutic effect of HT.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is a leading cause of cancer-related mortality [1]
In the linear fitting models or nonlinear fitting models of the four experimental groups, the regression equation for the therapeutic ultrasound (TUS) + MB + HT group indicated the strongest relationship between HT time and temperature (R2 = 0.87 for the linear regression model; R2 = 0.88 for the nonlinear regression model)
These results indicated significantly higher temperatures in the treated areas in the TUS + MB + HT and MB + HT groups versus
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is a leading cause of cancer-related mortality [1]. Traditional curative strategies include surgical resection, liver transplantation, chemotherapy, radiation therapy, and thermal therapy [2, 3]. The appropriate selection of curative strategies contributes to the overall survival rates in patients. The optimal choice of curative surgery for patients with HCC mainly depends on the early stage tumor and a good functional liver reserve. A majority of HCC patients are often diagnosed at later stages when the tumors cannot be surgically removed [4]. Non-surgical treatments play an important role in the palliative treatment of HCC
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