Alyssa Eade, MD (she/her/hers)
Resident
Harbor-UCLA Medical Center
Los Angeles, California, United States
Carolina Celades, MD
National Institutes of Health
Bethesda, Maryland, United States
Meghali Goswami, PhD
National Institutes of Health
Bethesda, Maryland, United States
Nicole Russell, BS
TCU School of Medicine
Fort Worth, Texas, United States
Emily C. Smith, PhD
Staff Scientist
NIH
Bethesda, Maryland, United States
Kirsten Remmert, PhD
Staff Scientist
NIH
Bethesda, Maryland, United States
Priyanka Desai, PhD
Post-doctoral fellow
NIH
Bethesda, Maryland, United States
Jason Ho, MD
National Institutes of Health
Bethesda, Maryland, United States
Justine Burke, BS
National Institutes of Health
Bethesda, Maryland, United States
Craig Thomas, PhD
National Institutes of Health
Bethesda, Maryland, United States
Renee Donahue, PhD
National Institutes of Health
Bethesda, Maryland, United States
Jonathan Hernandez, MD
Principal Investigator
NIH
Bethesda, Maryland, United States
Sophia Xiao, BA
Medical Student
National Institutes of Health (NIH)
Bethesda, Maryland, United States
Hepatic artery infusion pump floxuridine is an increasingly employed management strategy for patients with liver-limited colorectal liver metastases. However, floxuridine results in biliary injury, which limits the amount of drug administered and thereby its efficacy in order to avoid biliary sclerosis. To mitigate the injury, dexamethasone (a potent immunosuppressant) is administered concomitantly with floxuridine, although the immune pathways activated by the injury are unstudied.
Methods:
Serum samples were collected from 9 patients undergoing hepatic artery infusion pump therapy at baseline and following two weeks of floxuridine/dexamethasone treatment (no systemic therapy). Autologous plasma perfusate was collected following 96 hours of ex vivo perfusion of cystic ducts (n=2) treated with floxuridine. All samples were evaluated with the Olink Target 96 Immuno-Oncology panel.
Results:
Following 96 hours of floxuridine treatment, a significant increase (≥100% change) in IL-13 levels was observed in perfusate of ex vivo cystic duct compared to control perfusates. IL-10 demonstrated similar elevation (≥100% change). Correlation with patient serum demonstrated significant elevation of IL-13 levels following two weeks of floxuridine/dexamethasone treatment and significantly decreased levels of IL-6. Further investigation demonstrated no correlation of IL-13 levels with liver function test levels (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, direct and total bilirubin) during this time frame.
Conclusions:
Our data suggests that IL-13, a well-established promoter of hepatic fibrosis, may play a role in biliary injury following long-term (multiple cycles) floxuridine treatment. Further investigation of IL-13 throughout the treatment course may aid in the development of mitigating therapies.