Short Duration 9-cis Retinoid Acid Therapy is Sufficient to Improve Functional Lymphatic Drainage in Post-Surgical Lymphedema
Gene K. Lee, MD, MPH, David P. Perrault, BS, Antoun Bouz, BS, Austin J. Pourmoussa, MS, Daniel Gardner, BS, Maxwell Johnson, MS, Sun Young Park, MS, Athanasios Bramos, MD, Eun Kyung Park, MS, Young Jin N. Seong, BS, Sunju Lee, PhD, Lia E. Jung, MS, Dongwon Choi, PhD, Young-Kwon Hong, PhD, Alex K. Wong, MD, FACS.
University of Southern California, Los Angeles, CA, USA.
Purpose 9-cis Retinoic Acid (9-cis RA), prevents postsurgical lymphedema and is associated with increased lymphangiogenesis and lymphatic clearance. In this study, we sought to determine if shorter durations of 9-cis RA therapy were sufficient to maintain the functional effect on post-surgical lymphatic clearance.
Methods: Fifty C57BL/6 mice underwent surgical induction of tail lymphedema. Treatment groups (n=10) included injection of 9-cis RA starting on post-operative day (POD) zero for either 7, 7 days at POD 7, 14, and 45 days. The control group was injected with a vehicle control for 45 days. On POD 42, indocyanine green (ICG) lymphangiography was performed. Lymphatic fluid clearance was quantified over time with Image J and student-t tests were calculated between each group at various time points using GraphPad Prism 6.
*Significant (p-value < 0.05) difference between the control group and all other treatment groups
Figure 1. Graphical representation of tail ICG clearance over a span of 120 hours in the control and experimental groups.
Conclusions: The improvement in functional lymphatic flow in post-surgical lymphedema by 9-cis RA is present with 7 days, 7 days of delayed, 14 days and 45 days of therapy. The percent change in tail fluorescence on POD 42, upon injection of ICG as measured by SPY lymphangiography was significantly lower in all experimental groups overtime, compared to the vehicle control. 9-cis RA is a promising therapy for post-surgical lymphedema, even at shorter durations of therapy. A minimal effect dosing regimen has the potential to limit side effects of 9-cis RA systemic therapy.
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