An Experimental Animal Model for Head and Neck Lymphedema
Giulia Daneshgaran, BS, Connie B. Paik, BS, Michael N. Cooper, BA, Wan Jiao, MD, PhD, Ivetta Vorobyova, BS, Tea Jashashvili, MD, PhD, Yang Chai, DDS, PhD, Alex K. Wong, MD.
University of Southern California, Los Angeles, CA, USA.
PURPOSE: Head and neck lymphedema (HNL) is a disfiguring disease affecting over 75% of patients treated for head and neck cancer. The mainstay of HNL treatment is achieved through conservative measures with varying rates of success and poor long-term patient adherence. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies, which can offer improved results compared to standard conservative therapies. However, no animal model for HNL has been described in the literature to date. The purpose of this study is to describe the first reproducible rat model for head and neck lymphedema.
METHODS: Thirty-six (36) rats were split into 2 groups: 1) 18 experimental animals received the combined lymphatic injury protocol, 2) 18 control animals received sham surgery. The combined lymphatic injury protocol consisted of superficial and deep cervical lymph node dissection followed by cervical irradiation. Fluorescence imaging was performed to map the cervical lymphatic network in experimental animals and identify lymph nodes for dissection (Figure). Outcomes measured at day 0, 15 and 30 included neck circumference, cheek-to-cheek distance and magnetic resonance imaging (MRI) of the head and neck. MRI analysis was performed to quantify fat volume present within the head and neck region. Statistical analysis was performed using Student's t-test to compare outcomes between groups and between time points.
RESULTS: Postsurgical lymphedema was observed 94% of the time in the experimental group (17/18). When comparing the two groups, experimental animals were observed to have significantly more growth in all head and neck measures at day 15 (P<0.01) and day 30 (P<0.001). At day 30, experimental animals experienced 11% more growth in neck circumference from their preoperative state compared to control animals (P<0.0001), 9% more growth in cheek-to-cheek distance (P=0.0004), and 21% more growth in fat volume (P<0.0001). Within the experimental group, a significant change in fat volume was observed between day 15 and day 30 (P<0.05). In contrast, no significant differences were observed in outcomes for control animals over time.
CONCLUSION: Our results reveal that experimental animals receiving the combined lymphatic injury protocol developed changes consistent with postsurgical head and neck lymphedema, as evidenced by significant growth in all head and neck measures compared to control animals. In conclusion, we demonstrate that combined lymphatic injury in rats leads to a reproducible model of head and neck lymphedema.
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