{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:04:34Z","timestamp":1792447474934,"version":"4.5.0"},"reference-count":53,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":959,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jvsvenous.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Vascular Surgery: Venous and Lymphatic Disorders"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1016\/j.jvsv.2021.09.004","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T10:45:17Z","timestamp":1632739517000},"page":"966-975.e1","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"title":["A systematic review of pharmacologic and cell-based therapies for treatment of lymphedema (2010-2021)"],"prefix":"10.1016","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-8687","authenticated-orcid":false,"given":"James","family":"Walker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameera","family":"Tanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Roake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Lyons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jvsv.2021.09.004_bib1","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/nm.2545","article-title":"The lymphatic vasculature in disease","volume":"17","author":"Alitalo","year":"2011","journal-title":"Nat Med"},{"key":"10.1016\/j.jvsv.2021.09.004_bib2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1161\/CIRCRESAHA.115.306544","article-title":"Lymphatic system in cardiovascular medicine","volume":"118","author":"Aspelund","year":"2016","journal-title":"Circ Res"},{"key":"10.1016\/j.jvsv.2021.09.004_bib3","first-page":"81","article-title":"Lymphoedema","volume":"37","author":"Lyons","year":"2019","journal-title":"Surg Oxf"},{"key":"10.1016\/j.jvsv.2021.09.004_bib4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/lrb.2018.0084","article-title":"LIMPRINT: health-related quality of life in adult patients with chronic edema","volume":"17","author":"Mercier","year":"2019","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1101\/gad.303776.117","article-title":"Lymphangiogenesis guidance by paracrine and pericellular factors","volume":"31","author":"Vaahtomeri","year":"2017","journal-title":"Genes Dev"},{"key":"10.1016\/j.jvsv.2021.09.004_bib6","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1152\/physrev.00006.2020","article-title":"Development and physiological functions of the lymphatic system\u2014insights from genetic studies of lymphedema","volume":"101","author":"Martin-Almedina","year":"2021","journal-title":"Physiol Rev"},{"key":"10.1016\/j.jvsv.2021.09.004_bib7","doi-asserted-by":"crossref","first-page":"552","DOI":"10.7861\/clinmedicine.17-6-552","article-title":"An approach to familial lymphoedema","volume":"17","author":"Jones","year":"2017","journal-title":"Clin Med (Lond)"},{"key":"10.1016\/j.jvsv.2021.09.004_bib8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1196\/annals.1413.014","article-title":"Estimating the population burden of lymphedema","volume":"1131","author":"Rockson","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.jvsv.2021.09.004_bib9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41572-019-0072-5","article-title":"Cancer-associated secondary lymphoedema","volume":"5","author":"Rockson","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.jvsv.2021.09.004_bib10","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jvsv.2020.03.006","article-title":"A\u00a0systematic review of guidelines for lymphedema and the need for contemporary intersocietal guidelines for the management of lymphedema","volume":"8","author":"O\u2019Donnell","year":"2020","journal-title":"J\u00a0Vasc Surg Venous Lymphat Disord"},{"key":"10.1016\/j.jvsv.2021.09.004_bib11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yjmcc.2019.06.002","article-title":"Lymphatic system identification, pathophysiology and therapy in the cardiovascular diseases","volume":"133","author":"Hu","year":"2019","journal-title":"J\u00a0Mol Cell Cardiol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib12","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med"},{"key":"10.1016\/j.jvsv.2021.09.004_bib13","series-title":"Cochrane handbook for systematic reviews of interventions, version 6.2 (updated February 2021)","article-title":"Chapter 8: assessing risk of bias in a randomized trial","author":"Higgins","year":"2021"},{"key":"10.1016\/j.jvsv.2021.09.004_bib14","series-title":"Cochrane handbook for systematic reviews of interventions, version 6.2 (updated February 2021)","article-title":"Chapter 14: completing \u201csummary of findings\u201d tables and grading the certainty of the evidence","author":"Sch\u00fcnemann","year":"2021"},{"key":"10.1016\/j.jvsv.2021.09.004_bib15","doi-asserted-by":"crossref","first-page":"e123775","DOI":"10.1172\/jci.insight.123775","article-title":"Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema","volume":"3","author":"Rockson","year":"2018","journal-title":"JCI Insight"},{"key":"10.1016\/j.jvsv.2021.09.004_bib16","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/cid\/cis486","article-title":"Doxycycline improves filarial lymphedema independent of active filarial infection: a randomized controlled trial","volume":"55","author":"Mand","year":"2012","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.jvsv.2021.09.004_bib17","first-page":"1471","article-title":"Effectiveness and safety of a product containing diosmin, coumarin, and arbutin (Linfadren\u00ae) in addition to complex decongestive therapy on management of breast cancer-related lymphedema","volume":"27","author":"Cacchio","year":"2019","journal-title":"Support Care Cancer"},{"key":"10.1016\/j.jvsv.2021.09.004_bib18","first-page":"805","article-title":"Lymphatic edema of the lower limbs after orthopedic surgery: results of a randomized, open-label clinical trial with a new extended-release preparation","volume":"29","author":"Lessiani","year":"2015","journal-title":"J\u00a0Biol Regul Homeost Agents"},{"key":"10.1016\/j.jvsv.2021.09.004_bib19","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3390\/nu11051021","article-title":"Sodium selenite alleviates breast cancer-related lymphedema independent of antioxidant defense system","volume":"11","author":"Han","year":"2019","journal-title":"Nutrients"},{"key":"10.1016\/j.jvsv.2021.09.004_bib20","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3109\/14653249.2011.594791","article-title":"Autologous stem cells for the treatment of post-mastectomy lymphedema: a pilot study","volume":"13","author":"Maldonado","year":"2011","journal-title":"Cytotherapy"},{"key":"10.1016\/j.jvsv.2021.09.004_bib21","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/lrb.2019.0064","article-title":"A\u00a0randomized controlled trial comparing platelet-rich plasma, low-level laser therapy, and complex decongestive physiotherapy in patients with lower limb lymphedema","volume":"18","author":"Akgul","year":"2020","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.breast.2020.08.008","article-title":"Calorie restriction and synbiotics effect on quality of life and edema reduction in breast cancer-related lymphedema, a clinical trial","volume":"54","author":"Vafa","year":"2020","journal-title":"Breast"},{"key":"10.1016\/j.jvsv.2021.09.004_bib23","first-page":"128","article-title":"Validation of the lymphedema life impact scale (LLIS): a condition-specific measurement tool for persons with lymphedema","volume":"48","author":"Weiss","year":"2015","journal-title":"Lymphology"},{"key":"10.1016\/j.jvsv.2021.09.004_bib24","first-page":"13","article-title":"A\u00a0quality of life measure for limb lymphoedema (LYMQOL)","volume":"5","author":"Keeley","year":"2010","journal-title":"J\u00a0Lymphoedema"},{"key":"10.1016\/j.jvsv.2021.09.004_bib25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/j.1875-9114.1986.tb03459.x","article-title":"Ketoprofen: a review of its pharmacologic and clinical properties","volume":"6","author":"Kantor","year":"1986","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.jvsv.2021.09.004_bib26","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1080\/01635581.2019.1616781","article-title":"The effects of synbiotic supplementation on antioxidant capacity and arm volumes in survivors of breast cancer-related lymphedema","volume":"72","author":"Navaei","year":"2020","journal-title":"Nutr Cancer"},{"key":"10.1016\/j.jvsv.2021.09.004_bib27","first-page":"1","article-title":"The effects of synbiotic supplementation on serum inflammatory markers and edema volume in breast cancer survivors with lymphedema","volume":"19","author":"Vafa","year":"2020","journal-title":"EXCLI J"},{"key":"10.1016\/j.jvsv.2021.09.004_bib28","first-page":"1","article-title":"The diagnosis and treatment of peripheral lymphedema: 2013 consensus document of the International Society of Lymphology","volume":"46","year":"2013","journal-title":"Lymphology"},{"key":"10.1016\/j.jvsv.2021.09.004_bib29","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jaad.2017.03.022","article-title":"Lymphedema: pathophysiology and clinical manifestations","volume":"77","author":"Grada","year":"2017","journal-title":"J\u00a0Am Acad Dermatol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib30","series-title":"Basic lymphoedema management: treatment and prevention of problems associated with lymphatic filariasis","author":"Dreyer","year":"2002"},{"key":"10.1016\/j.jvsv.2021.09.004_bib31","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1371\/journal.ppat.0020092","article-title":"Doxycycline reduces plasma VEGF-C\/sVEGFR-3 and improves pathology in lymphatic filariasis","volume":"2","author":"Debrah","year":"2006","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.jvsv.2021.09.004_bib32","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1056\/NEJM199310143291604","article-title":"Treatment of lymphedema of the arms and legs with 5,6-benzo-[alpha]-pyrone","volume":"329","author":"Casley-Smith","year":"1993","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jvsv.2021.09.004_bib33","first-page":"39","article-title":"Evaluation by lymphoscintigraphy of the effect of a micronized flavonoid fraction (Daflon 500 mg) in the treatment of upper limb lymphedema","volume":"14","author":"Pecking","year":"1995","journal-title":"Int Angiol J Int Union Angiol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib34","doi-asserted-by":"crossref","first-page":"eaal3920","DOI":"10.1126\/scitranslmed.aal3920","article-title":"Leukotriene B4 antagonism ameliorates experimental lymphedema","volume":"9","author":"Tian","year":"2017","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jvsv.2021.09.004_bib35","doi-asserted-by":"crossref","first-page":"e8380","DOI":"10.1371\/journal.pone.0008380","article-title":"Anti-inflammatory pharmacotherapy with ketoprofen ameliorates experimental lymphatic vascular insufficiency in mice","volume":"4","author":"Nakamura","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.jvsv.2021.09.004_bib36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mvr.2015.09.001","article-title":"Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model","volume":"102","author":"Ackermann","year":"2015","journal-title":"Microvasc Res"},{"key":"10.1016\/j.jvsv.2021.09.004_bib37","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1111\/jdv.14345","article-title":"Doxycycline as an anti-inflammatory agent: updates in dermatology","volume":"31","author":"Henehan","year":"2017","journal-title":"J\u00a0Eur Acad Dermatol Venereol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/stem.2751","article-title":"Concise review: cell therapy for critical limb ischemia: an integrated review of preclinical and clinical studies","volume":"36","author":"Qadura","year":"2018","journal-title":"Stem Cells"},{"key":"10.1016\/j.jvsv.2021.09.004_bib39","doi-asserted-by":"crossref","first-page":"e29080","DOI":"10.4161\/onci.29080","article-title":"Bone marrow-derived cells are implicated as a source of lymphatic endothelial progenitors in human breast cancer","volume":"3","author":"van\u2019t Hull","year":"2014","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.jvsv.2021.09.004_bib40","first-page":"CD003140","article-title":"Benzopyrones for reducing and controlling lymphoedema of the limbs","volume":"2","author":"Badger","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.jvsv.2021.09.004_bib41","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/toxsci\/kfh162","article-title":"Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity","volume":"80","author":"Vassallo","year":"2004","journal-title":"Toxicol Sci"},{"key":"10.1016\/j.jvsv.2021.09.004_bib42","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1371\/journal.pmed.0030254","article-title":"Inflammatory manifestations of experimental lymphatic insufficiency","volume":"3","author":"Tabibiazar","year":"2006","journal-title":"PLoS Med"},{"key":"10.1016\/j.jvsv.2021.09.004_bib43","first-page":"e6300","article-title":"Pharmacotherapy agents in lymphedema treatment: a systematic review","volume":"11","author":"Forte","year":"2019","journal-title":"Cureus"},{"key":"10.1016\/j.jvsv.2021.09.004_bib44","first-page":"CD003143","article-title":"Antibiotics\/anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs","volume":"2","author":"Badger","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.jvsv.2021.09.004_bib45","unstructured":"U.S. Food and Drug Administration (FDA). FDA drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2015. Available at: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory. Accessed June 1, 2021."},{"key":"10.1016\/j.jvsv.2021.09.004_bib46","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2165\/00063030-200620060-00007","article-title":"An experimental model for the study of lymphedema and its response to therapeutic lymphangiogenesis","volume":"20","author":"Cheung","year":"2006","journal-title":"BioDrugs"},{"key":"10.1016\/j.jvsv.2021.09.004_bib47","first-page":"e5887","article-title":"Use of gene transfer vectors in lymphedema treatment: a systematic review","volume":"11","author":"Forte","year":"2019","journal-title":"Cureus"},{"key":"10.1016\/j.jvsv.2021.09.004_bib49","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.bjps.2020.05.009","article-title":"Phase 1 Lymfactin\u00ae study: short-term safety of combined adenoviral VEGF-C and lymph node transfer treatment for upper extremity lymphedema","volume":"73","author":"Hartiala","year":"2020","journal-title":"J\u00a0Plast Reconstr Aesthet Surg"},{"key":"10.1016\/j.jvsv.2021.09.004_bib50","unstructured":"Herantis Pharma Plc. Herantis Pharma Plc completes patient recruitment and treatment in phase 2 AdeLE trial in breast cancer associated lymphedema. 2019. Available at: https:\/\/herantis.com\/press-releases\/herantis-pharma-plc-completes-patient-recruitment-and-treatment-in-phase-2-adele-trial-in-breast-cancer-associated-lymphedema\/. Accessed June 1, 2021."},{"key":"10.1016\/j.jvsv.2021.09.004_bib51","unstructured":"Herantis Pharma Plc. Herantis announces inconclusive results from phase II study with Lymfactin in breast cancer related lymphedema. 2021. Available at: https:\/\/herantis.com\/press-releases\/herantis-announces-inconclusive-results-from-phase-ii-study-with-lymfactin-in-breast-cancer-related-lymphedema\/. Accessed June 1, 2021."},{"key":"10.1016\/j.jvsv.2021.09.004_bib52","first-page":"316","article-title":"Chronic edema of the lower extremities: international consensus recommendations for compression therapy clinical research trials","volume":"31","author":"Stout","year":"2012","journal-title":"Int Angiol J Int Union Angiol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib53","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1089\/lrb.2017.0027","article-title":"Stem cell therapy using bone marrow-derived mononuclear cells in treatment of lower limb lymphedema: a randomized controlled clinical trial","volume":"16","author":"Ismail","year":"2018","journal-title":"Lymphat Res Biol"},{"key":"10.1016\/j.jvsv.2021.09.004_bib54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s13139-018-0565-2","article-title":"Procedural recommendations for lymphoscintigraphy in the diagnosis of peripheral lymphedema: the Genoa protocol","volume":"53","author":"Villa","year":"2019","journal-title":"Nucl Med Mol Imaging"}],"container-title":["Journal of Vascular Surgery: Venous and Lymphatic Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213333X21004868?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213333X21004868?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T07:02:56Z","timestamp":1761980576000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213333X21004868"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["S2213333X21004868"],"URL":"https:\/\/doi.org\/10.1016\/j.jvsv.2021.09.004","relation":{},"ISSN":["2213-333X"],"issn-type":[{"value":"2213-333X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A systematic review of pharmacologic and cell-based therapies for treatment of lymphedema (2010-2021)","name":"articletitle","label":"Article Title"},{"value":"Journal of Vascular Surgery: Venous and Lymphatic Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jvsv.2021.09.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 by the Society for Vascular Surgery. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}