{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:19:26Z","timestamp":1792095566002,"version":"4.4.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1K08HL132110\u201001A1"],"award-info":[{"award-number":["1K08HL132110\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Surgical Oncology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>Previously, we have shown that 9\u2010cis retinoic acid (9\u2010cis RA) stimulates lymphangiogenesis and limits postsurgical lymphedema in animal models when administered via daily intraperitoneal injections. In this study, we investigate whether a single\u2010use depot 9\u2010cis 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hind limb lymphedema was induced via surgical lymphadenectomy and irradiation. Animals were divided into two treatment groups: (1) 9\u2010cis RA DDS, (2) placebo DDS. Outcomes measured included paw thickness, lymphatic clearance and density, epidermal thickness, and collagen deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control animals, 9\u2010cis RA\u2010treated animals had significantly less paw swelling from postoperative week 3 (<jats:italic>P<\/jats:italic>\u2009=\u2009.04) until the final timepoint at week 6 (<jats:italic>P<\/jats:italic>\u2009=\u2009.0007). Moreover, 9\u2010cis RA\u2010treated animals had significantly faster lymphatic clearance (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05), increased lymphatic density (<jats:italic>P<\/jats:italic>\u2009=\u2009.04), reduced lymphatic vessel size (<jats:italic>P<\/jats:italic>\u2009=\u2009.02), reduced epidermal hyperplasia (<jats:italic>P<\/jats:italic>\u2009=\u2009.04), and reduced collagen staining (<jats:italic>P<\/jats:italic>\u2009=\u2009.10).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Animals receiving 9\u2010cis RA sustained\u2010release implants at the time of surgery had improved lymphatic function and structure, indicating reduced lymphedema progression. Thus, we demonstrate that 9\u2010cis RA contained within a single\u2010use depot DDS has favorable properties in limiting pathologic responses to lymphatic injury and may be an effective strategy against secondary lymphedema.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jso.25587","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T04:19:36Z","timestamp":1561522776000},"page":"100-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prevention of postsurgical lymphedema via immediate delivery of sustained\u2010release 9\u2010cis retinoic acid to the lymphedenectomy site"],"prefix":"10.1002","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-5762","authenticated-orcid":false,"given":"Giulia","family":"Daneshgaran","sequence":"first","affiliation":[{"name":"Albert Einstein College of Medicine, Jack and Pearl Resnick Campus New York New York"},{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie B.","family":"Paik","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"},{"name":"Tulane University School of Medicine New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lo","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Jiao","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Kwon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4068-5230","authenticated-orcid":false,"given":"Alex K.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of University of Southern California University of Southern California Los Angeles 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