{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:56:23Z","timestamp":1786470983337,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18ek0109277h0002"],"award-info":[{"award-number":["18ek0109277h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18lk0201055h0003"],"award-info":[{"award-number":["18lk0201055h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Kaposiform lymphangiomatosis (KLA) has recently been distinguished as a novel subtype of generalized lymphatic anomaly (GLA), and is characterized by foci of spindle endothelial cells amid a background of malformed lymphatic channels. The etiology of these diseases remains unknown and diagnosis is confounded by their similar clinical findings. This study aimed to clarify differences in the clinical findings and plasma cytokine profiles of GLA and KLA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Clinical features data of GLA and KLA patients were obtained from a national survey. Differences in clinical findings, plasma levels of cytokines, and survival were analyzed. Plasma was obtained from healthy controls and GLA and KLA patients. Thirty\u2010six angiogenic and lymphangiogenic factors were evaluated for cytokine concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010one patients with GLA and 11 with KLA were recruited. Mediastinal masses, hemorrhagic pericardial and pleural effusion, coagulation disorders, and thrombocytopenia were more frequent in KLA than in GLA. KLA had a significantly poorer outcome than GLA (<jats:italic>P\u00a0<\/jats:italic>=\u00a00.044). Soluble VEGFR3, angiopoietin 2, HGF, soluble HER2, tenascin C, and soluble HGFR levels were higher in KLA. Notably, soluble VEGFR3 and angiopoietin 2 levels were approximately 10\u2010fold higher than those of other molecules measured. However, soluble VEGFR1 and soluble TIE2 were lower in KLA than in GLA and the controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with KLA have an unfavorable prognosis and serious symptoms (hemorrhagic pleural effusion and coagulation disorders). Our data indicate that eight angiogenic cytokines might be potential biomarkers of KLA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.27878","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T18:24:36Z","timestamp":1560795876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Potential biomarkers of kaposiform lymphangiomatosis"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-4448","authenticated-orcid":false,"given":"Michio","family":"Ozeki","sequence":"first","affiliation":[{"name":"Department of Pediatrics Gifu University Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7345-8491","authenticated-orcid":false,"given":"Akifumi","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Fujino","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery National Center for Child Health and Development  Setagaya\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Institute for NanoSuit Research Preeminent Medical Photonics Education &amp; Research Center Hamamatsu University School of Medicine  Hamamatsu Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Fukao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Graduate School of Medicine Gifu University  Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2014.07.006"},{"key":"e_1_2_8_3_1","unstructured":"International Society for the Study of Vascular Anomalies: ISSVA classification for Vascular Anomalies(approved at the May 2018 General Assembly in Amsterdam the Netherlands)http:\/\/issva.org\/classification(accessed June 2018)."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.10.013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25914"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25278"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26716"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1013217"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"e00384","DOI":"10.1002\/rcr2.384","article-title":"Diffuse pulmonary lymphangiomatosis treated with bevacizumab","volume":"7","author":"Onyeforo E","year":"2018","journal-title":"Respirol Case Rep"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-016-9537-2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal4712"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2006.00178.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71614"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0390-0"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9595-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181353"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00217-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvsv.2017.05.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i7.964"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2012.727028"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2003.10.006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63851-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.11.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3327"},{"key":"e_1_2_8_25_1","first-page":"139","article-title":"HIF\u20101\u03b1 contributes to tube malformation of human lymphatic endothelial cells by upregulating VEGFR\u20103","volume":"54","author":"Han T","year":"2019","journal-title":"Int J Oncol"},{"key":"e_1_2_8_26_1","first-page":"1399","article-title":"Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF\u2010A","volume":"9","author":"Lamszus K","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10121"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep27186"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600763"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.190546"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-3257"}],"container-title":["Pediatric Blood &amp; 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