{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:51:14Z","timestamp":1790376674275,"version":"4.1.0"},"reference-count":25,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Lymphatic malformations (LMs) are congenital vascular anomalies with limited treatment options. Eppikajutsuto, a traditional Japanese (Kampo) herbal medicine, is commonly used to treat inflammatory conditions and has been reported to reduce lesion volume in patients with LMs; however, data on its effectiveness in pediatric patients are needed.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the association of eppikajutsuto with reduced LM lesion volume in pediatric patients with LMs.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This open-label nonrandomized clinical trial was conducted from April 14, 2021, to September 30, 2024, at multiple centers in Japan. Eligible participants were 18 years or younger with a confirmed diagnosis of LM by imaging. Data were analyzed from October 14, 2024, to March 4, 2025.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Participants received eppikajutsuto granules (0.6 g\/kg\/d to \u22647.5 g\/d) orally for 6 months.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the proportion of patients achieving a 20% or greater reduction in lesion volume, measured with magnetic resonance imaging volumetry at baseline and 6 months. Secondary outcomes included a 50% or greater reduction in lesion volume, median shrinkage rate, improvement in quality of life, and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 19 patients (10 male [52.6%]; mean [SD] age, 24.1 [29.4] months) were enrolled. A total of\u200910 patients (52.6%; 90% CI, 32.0%-73.0%) achieved a 20% or greater reduction in lesion volume at 6 months. The median shrinkage rate was 22.9% (IQR, \u2212142.3% to 96.0%). No serious adverse events occurred, and medication adherence of 70% or greater was observed in 17 of 19 patients (89.5%).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this nonrandomized clinical trial of children with LMs, eppikajutsuto was associated with a reduction in lesion volume and was well tolerated. Further studies, including randomized clinical trials, are warranted to confirm these findings.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n Japan Registry of Clinical Trials Identifier:\n jRCTs041210007<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.40897","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:01:51Z","timestamp":1762185711000},"page":"e2540897","source":"Crossref","is-referenced-by-count":1,"title":["Eppikajutsuto for Treatment of Lymphatic Malformations in Children"],"prefix":"10.1001","volume":"8","author":[{"given":"Keiko","family":"Ogawa-Ochiai","sequence":"first","affiliation":[{"name":"Kampo Clinical Center, Hiroshima University Hospital, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seisho","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Kanazawa University Hospital, Kanazawa City, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isamu","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima City, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Tazuke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan"},{"name":"Pediatric Surgery, Hyogo Medical University, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Fujino","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Radiology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Li","sequence":"additional","affiliation":[{"name":"Kampo Clinical Center, Hiroshima University Hospital, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonari","family":"Nomura","sequence":"additional","affiliation":[{"name":"Pediatric Surgery, University of Osaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Hoshi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Shimojima","sequence":"additional","affiliation":[{"name":"Division of Surgery, Department of Surgical Specialties, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Ochi","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimpei","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Kanazawa University Hospital, Kanazawa City, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, St Marianna University School of Medicine, Kawasaki, 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