{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:14:54Z","timestamp":1792253694431,"version":"4.4.0"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"20","funder":[{"DOI":"10.13039\/100005492","name":"Stanford University","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100005492","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,18]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Lymphedema is a common condition affecting millions around the world that still lacks approved medical therapy. Because ketoprofen, an NSAID, has been therapeutic in experimental lymphedema, we evaluated its efficacy in humans.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We first performed an exploratory open-label trial. Patients with either primary or secondary lymphedema received ketoprofen 75 mg by mouth 3 times daily for 4 months. Subjects were evaluated for changes in histopathology, with skin thickness, limb volume, and tissue bioimpedance changes serving as secondary endpoints. Based on our encouraging findings, we next conducted a placebo-controlled trial, with the primary outcome defined as a change in skin thickness, as measured by skin calipers. Secondary endpoints for this second study included histopathology, limb volume, bioimpedance, and systemic inflammatory mediators.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    We enrolled 21 lymphedema patients in the open-label trial, from November 2010 to July 2011. Histopathology and skin thickness were significantly improved at 4 months compared with baseline. In the follow-up, double-blind, placebo-controlled trial, we enrolled 34 patients from August 2011 to October 2015, with 16 ketoprofen recipients and 18 placebo-treated subjects. No serious adverse events occurred. The ketoprofen recipients demonstrated reduced skin thickness, as well as improved composite measures of histopathology and decreased plasma granulocyte CSF (G-CSF) expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    These 2 exploratory studies together support the utility of targeted antiinflammatory therapy with ketoprofen in patients with lymphedema. Our results highlight the promise of such approaches to help restore a failing lymphatic circulation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRATION.<\/jats:bold>\n                    ClinicalTrials.gov NCT02257970.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.123775","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T11:01:49Z","timestamp":1539774109000},"source":"Crossref","is-referenced-by-count":124,"title":["Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1253-474X","authenticated-orcid":true,"given":"Stanley G.","family":"Rockson","sequence":"first","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-318X","authenticated-orcid":true,"given":"Wen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Medicine, VA Palo Alto Health Care System\/Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3266-9238","authenticated-orcid":true,"given":"Xinguo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine, VA Palo Alto Health Care System\/Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Zampell","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Mehrara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Sampson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Roche","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-7422","authenticated-orcid":true,"given":"Mark R.","family":"Nicolls","sequence":"additional","affiliation":[{"name":"Department of Medicine, VA Palo Alto Health Care System\/Stanford University, Palo Alto, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s11936-012-0170-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71608"},{"key":"B3"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25458"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1413.014"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2017.29033.sr"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2006.05.009"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00306.2011"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2009.0002"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0401fje"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71607"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034008"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030254"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008380"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(91)90185-Q"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2010.00963.x"},{"issue":"389","key":"B17","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aal3920","article-title":"Leukotriene B4 antagonism ameliorates experimental lymphedema","volume":"9","author":"Tian","year":"2017","journal-title":"Sci Transl Med"},{"issue":"2","key":"B18","first-page":"78","article-title":"Assessment of truncal edema following breast cancer treatment using modified Harpenden skinfold calipers","volume":"28","author":"Roberts","year":"1995","journal-title":"Lymphology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2354.2002.00312.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1075-122X.2004.21458.x"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049940"},{"issue":"1","key":"B22","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18010171","article-title":"Inflammatory Manifestations of Lymphedema","volume":"18","author":"Ly","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070703"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.03.002"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74854"},{"issue":"200","key":"B26","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3006674","article-title":"Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension","volume":"5","author":"Tian","year":"2013","journal-title":"Sci Transl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2006.4404"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004171"},{"key":"B29","unstructured":"[No authors listed]. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDS) can cause heart attacks and strokes. Food and Drug Administration. https:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm451800.htm Updated Feburary 26, 2018. Accessed September 18, 2018"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2354.1995.tb00047.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2010.0014"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/38\/3\/001"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052021"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/123775\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:40:20Z","timestamp":1779194420000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/123775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,18]]},"references-count":33,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2018,10,18]]},"published-print":{"date-parts":[[2018,10,18]]}},"alternative-id":["10.1172\/jci.insight.123775"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.123775","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,18]]},"article-number":"e123775"}}