{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:39Z","timestamp":1789106859250,"version":"build-2803163510"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In this exploratory study, we investigated plasma histamine concentration as a perioperative prognostic marker in dogs with mast cell tumours. Mast cell tumours exhibit marked heterogeneity in biological behaviour, and histological grading is widely used for prognostication; however, grading alone does not directly reflect tumour burden or residual disease following surgery. Histamine has a short half-life in the circulation, and persistently elevated plasma histamine levels may reflect continuous release from neoplastic mast cells. Although plasma histamine concentration has been proposed as a marker of prognosis and residual disease, its clinical relevance and optimal interpretation remain incompletely defined. Twenty-seven dogs that underwent surgical excision of mast cell tumours (29 surgeries) during a 28-month study period were included. Associations between plasma histamine concentration and survival outcomes were evaluated using Kaplan\u2013Meier survival analyses. Multivariable analyses were performed to explore factors associated with preoperative and postoperative plasma histamine concentration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dogs with elevated preoperative plasma histamine concentration (&amp;gt;1.0\u202fng\/mL) had significantly shorter progression-free intervals (PFIs) than those with low preoperative plasma histamine concentration (\u22641.0\u202fng\/mL). However, in multivariable analyses restricted to dogs with cutaneous mast cell tumours, preoperative plasma histamine concentration was confounded by tumour volume and was not an independent prognostic factor following adjustment. Postoperative plasma histamine concentration values were elevated in only a few cases, limiting formal survival analyses; nonetheless, multivariable analyses demonstrated a significant association between postoperative plasma histamine concentration and gross residual disease, suggesting that postoperative plasma histamine concentration may reflect macroscopic residual tumour but may lack sensitivity for microscopic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings suggest that preoperative plasma histamine concentration primarily reflects tumour burden in dogs with cutaneous mast cell tumours, whereas postoperative plasma histamine concentration is associated with macroscopic residual disease and may be less informative for detecting microscopic residual or metastatic disease. Plasma histamine concentration may serve as an adjunctive perioperative biomarker when interpreted in conjunction with established clinicopathological factors. Larger prospective studies are warranted to validate assay performance, refine cut-off values, and determine the clinical utility of plasma histamine concentration in canine mast cell tumours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1882434","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:30:23Z","timestamp":1789104623000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory analysis of perioperative plasma histamine concentrations in dogs with mast cell tumours"],"prefix":"10.3389","volume":"13","author":[{"given":"Akihiro","family":"Niwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Kadosawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref1","first-page":"335","volume-title":"Small Animal Clinical Oncology","author":"Thamm","year":"2013"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1177\/0300985810386469","article-title":"Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior","volume":"48","author":"Kiupel","year":"2011","journal-title":"Vet Pathol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1177\/030098588402100503","article-title":"Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs","volume":"21","author":"Patnaik","year":"1984","journal-title":"Vet Pathol"},{"key":"ref4","first-page":"199","article-title":"Metabolism of histamine in the dog","volume":"118","author":"Schayer","year":"1956","journal-title":"J Pharmacol Exp Ther"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.1939-1676.1990.tb03116.x","article-title":"Plasma histamine and gastrin concentrations in 17 dogs with mast cell tumors","volume":"4","author":"Fox","year":"1990","journal-title":"J Vet Intern Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/j.1939-1676.2003.tb02433.x","article-title":"Relationship of disease progression and plasma histamine concentrations in 11 dogs with mast cell tumors","volume":"17","author":"Ishiguro","year":"2003","journal-title":"J Vet Intern Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00580-010-0980-y","article-title":"Pre- and post-operative plasma histamine concentrations in 35 dogs with mast cell tumours","volume":"20","author":"van Gelderen","year":"2011","journal-title":"Comp Clin Pathol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1177\/030098589002700305","article-title":"Morphometric analyses of the skin of dogs with atopic dermatitis and correlations with cutaneous and plasma histamine and total serum IgE","volume":"27","author":"Wilkie","year":"1990","journal-title":"Vet Pathol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1292\/jvms.16-0550","article-title":"Incidence of anaphylactic reactions after propofol administration in dogs with elevated serum IgE concentrations","volume":"79","author":"Onuma","year":"2017","journal-title":"J Vet Med Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1007\/BF01972666","article-title":"Alterations in the circulatory system of anaesthetized dogs following administration of histamine and histamine H1- and H2-receptor antagonists in relation to plasma histamine levels","volume":"5","author":"Thermann","year":"1975","journal-title":"Agents Actions"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1111\/j.1365-2885.2007.00911.x","article-title":"Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs","volume":"30","author":"Guedes","year":"2007","journal-title":"J Vet Pharmacol Ther"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.2460\/ajvr.1988.49.10.1699","article-title":"Comparison of histamine release induced by morphine and oxymorphone administration in dogs","volume":"49","author":"Robinson","year":"1988","journal-title":"Am J Vet Res\u00c4i0"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"804","DOI":"10.2460\/javma.251.7.804","article-title":"Antihistaminic and cardiorespiratory effects of diphenhydramine hydrochloride in anesthetized dogs undergoing excision of mast cell tumors","volume":"251","author":"Sanchez","year":"2017","journal-title":"J Am Vet Med Assoc"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1007\/BF00300234","article-title":"Determination of subcutaneous tumor size in athymic (nude) mice","volume":"24","author":"Tomayko","year":"1989","journal-title":"Cancer Chemother Pharmacol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.jcpa.2014.07.004","article-title":"Correlation of nodal mast cells with clinical outcome in dogs with mast cell tumour and a proposed classification system for the evaluation of node metastasis","volume":"151","author":"Weishaar","year":"2014","journal-title":"J Comp Pathol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1111\/vco.12425","article-title":"Therapeutic impact of regional lymphadenectomy in canine stage II cutaneous mast cell tumours","volume":"16","author":"Marconato","year":"2018","journal-title":"Vet Comp Oncol"}],"container-title":["Frontiers in Veterinary 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