Predicting Future Liver Remnant Function and Growth Trajectory Using Novel MR Imaging Biomarkers

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PROJECT ABSTRACT Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths in the world. In fact, HCC is the fastest growing cause of all cancer deaths in the United States with a poor 5-year survival rate of 18%. The only curative therapies for HCC are liver transplantation or liver resection (partial hepatectomy) and for non-surgical candidates ablation. Malignant tumors within the liver, whether primary or secondary, are the most common indication for curative partial hepatectomies. However, many patients with HCC have underlying cirrhosis or some degree of liver dysfunction. As a result, the most severe complication after surgery remains post-hepatectomy liver failure with a mortality rate between 1.2 to 33.8%. Successful curative partial hepatectomy requires sufficient liver regeneration and function to avoid post- operative hepatic insufficiency. Currently, potential surgical candidates are identified by determining future liver remnant (FLR) volume. There are no clear guidelines for FLR volume in mild-moderate liver disease. It is known that portal blood flow is a key parameter driving liver hypertrophy but is not well understood. We hypothesize that there is a relationship between portal blood flow, FLR growth trajectory, and liver function. To investigate, we will perform partial hepatectomies in 7 healthy pigs with 3 controls undergoing a sham surgery. All 10 pigs will undergo magnetic resonance (MR) Imaging at 4 separate time points (pre-operative, post-operative day [POD] 0, between POD 6-8, and between POD 26-30) to evaluate for portal blood flow using a novel “4D flow” MR method, liver volume, and liver function. Our imaging time points will help assess the first two aims – demonstrating the utility of quantitative MR imaging biomarkers in predicting FLR function and growth trajectory, and also determining the relationship between FLR function and volume over time. Finally, we aim to determine the effects of portal hyperemia via a meal challenge to assess portal system accommodation and compliance as a predictive parameter. Our goal is to predict FLR function and growth to improve patient selection, pre-operative surgical planning, and outcomes through a series of three aims. The applicant, Devashish Joshi, MD, is a general surgery resident at the University of Wisconsin-Madison pursuing a career as a surgical oncologist and independent investigator. This fellowship would support his second year of dedicated research time with minimal clinical responsibilities. His sponsor, radiologist Dr. Scott Reeder, and co-sponsor, hepatobiliary surgical oncologist Dr. Sharon Weber, have significant track records of mentoring surgical trainees. They will guide and mentor Dr. Joshi in completing the proposed project to improve care in patients with liver cancer and build his foundations towards becoming a surgeon-scientist.