Daneshgaran G, Paik CB, Cooper MN, Sung C, Lo A, Jiao W, Park SY, Kim GH, Hong YK, Wong AK, et al.
Journal of surgical oncology. Date of publication 2020 Jan 1;volume 121(1):100-108.
1. J Surg Oncol. 2020 Jan;121(1):100-108. doi: 10.1002/jso.25587. Epub 2019 Jun 25.
Prevention of postsurgical lymphedema via immediate delivery of sustained-release
9-cis retinoic acid to the lymphedenectomy site.
Daneshgaran G(1)(2), Paik CB(2), Cooper MN(2)(3), Sung C(2), Lo A(2), Jiao W(2),
Park SY(2), Kim GH(4), Hong YK(5), Wong AK(2)(5).
Author information:
(1)Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, New York,
New York.
(2)Division of Plastic and Reconstructive Surgery, Keck School of Medicine of
University of Southern California, University of Southern California, Los
Angeles, California.
(3)Tulane University School of Medicine, New Orleans, Louisiana.
(4)Department of Dermatology, Keck School of Medicine of University of Southern
California, University of Southern California, Los Angeles, California.
(5)Department of Surgery, Keck School of Medicine of University of Southern
California, University of Southern California, Los Angeles, California.
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.
© 2019 Wiley Periodicals, Inc.
DOI: 10.1002/jso.25587
PMCID: PMC6930358
PMID: 31240729 [Indexed for MEDLINE]
