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The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma
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Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy

Nuclear Medicine Department, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
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Author to whom correspondence should be addressed.
Academic Editors: Nathan A. Berger and J. Mark Brown
Cancers 2021, 13(7), 1537; https://doi.org/10.3390/cancers13071537
Received: 8 February 2021 / Revised: 22 March 2021 / Accepted: 23 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Translational Studies of Obesity-Associated Hepatocellular Cancer)
Radioembolization of hepatic tumors is performed by injecting 90Y or 166Ho loaded spheres into the hepatic artery. A twofold tumor to normal liver absorbed dose ratio is commonly obtained. In order to improve tumoral cell killing while preserving lobule function, co-injection of arterial vasoconstrictor has been proposed, but without success: the hepatic arterial buffer response quickly inhibits the arterioles vasoconstriction. The aim of the study is to investigate whether it is possible to take benefit from this buffer response, by co-infusing a mesenteric arterial vasodilator in order to dump the hepatic lobules arterial flow. Animal studies evidencing such mechanism are reviewed. Some potential mesenteric vasodilators are identified and their safety profile discussed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in hepatocellular carcinoma (HCC), more frequent in obese subjects, and where ultra-selective spheres delivery is often not possible.
Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible. View Full-Text
Keywords: liver radioembolization; cancer therapy; dose optimization; TARE; SIRT liver radioembolization; cancer therapy; dose optimization; TARE; SIRT
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MDPI and ACS Style

Walrand, S.; Hesse, M.; d’Abadie, P.; Jamar, F. Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy. Cancers 2021, 13, 1537. https://doi.org/10.3390/cancers13071537

AMA Style

Walrand S, Hesse M, d’Abadie P, Jamar F. Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy. Cancers. 2021; 13(7):1537. https://doi.org/10.3390/cancers13071537

Chicago/Turabian Style

Walrand, Stephan, Michel Hesse, Philippe d’Abadie, and François Jamar. 2021. "Hepatic Arterial Buffer Response in Liver Radioembolization and Potential Use for Improved Cancer Therapy" Cancers 13, no. 7: 1537. https://doi.org/10.3390/cancers13071537

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