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Prevention of postsurgical lymphedema via immediate delivery of sustained‐release 9‐cis retinoic acid to the lymphedenectomy site
Author(s) -
Daneshgaran Giulia,
Paik Connie B.,
Cooper Michael N.,
Sung Cynthia,
Lo Andrea,
Jiao Wan,
Park Sun Young,
Kim Gene H.,
Hong YoungKwon,
Wong Alex K.
Publication year - 2020
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.25587
Subject(s) - medicine , lymphedema , lymphatic system , lymphangiogenesis , lymphatic vessel , hindlimb , retinoic acid , surgery , pathology , urology , cancer , metastasis , biochemistry , chemistry , breast cancer , gene
Background and objectives Previously, we have shown that 9‐cis retinoic acid (9‐cis RA) stimulates lymphangiogenesis and limits postsurgical lymphedema in animal models when administered via daily intraperitoneal injections. In this study, we investigate whether a single‐use depot 9‐cis RA drug delivery system (DDS) implanted at the site of lymphatic injury can mitigate the development of lymphedema in a clinically relevant mouse limb model. Methods Hind limb lymphedema was induced via surgical lymphadenectomy and irradiation. Animals were divided into two treatment groups: (1) 9‐cis RA DDS, (2) placebo DDS. Outcomes measured included paw thickness, lymphatic clearance and density, epidermal thickness, and collagen deposition. Results Compared with control animals, 9‐cis RA‐treated animals had significantly less paw swelling from postoperative week 3 ( P = .04) until the final timepoint at week 6 ( P = .0007). Moreover, 9‐cis RA‐treated animals had significantly faster lymphatic clearance ( P < .05), increased lymphatic density ( P = .04), reduced lymphatic vessel size ( P = .02), reduced epidermal hyperplasia ( P = .04), and reduced collagen staining ( P = .10). Conclusions Animals receiving 9‐cis RA sustained‐release implants at the time of surgery had improved lymphatic function and structure, indicating reduced lymphedema progression. Thus, we demonstrate that 9‐cis RA contained within a single‐use depot DDS has favorable properties in limiting pathologic responses to lymphatic injury and may be an effective strategy against secondary lymphedema.