{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:53:02Z","timestamp":1772517182050,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>(1) Background: Gallbladder mucosal erosion and\/or ulceration are illnesses associated with unexpected gallbladder intra-cystic bleeding (hemocholecyst), an under-reported problem in dogs. (2) Methods: Clinicopathological characteristics of 14 dogs with gallbladder erosion\/ulcer were investigated in this single-center retrospective study using clinical data and archived gallbladder tissues of client-owned dogs. (3) Results: Canine gallbladder erosion\/ulcer tends to occur in older, neutered dogs of various breeds. Vomiting, lethargy, and anorexia are common. Concurrent gallbladder rupture occurred in 5\/14 cases (35.7%), while rupture was absent in 6\/14 cases (42.8%) and undetermined in 3\/14 (21.4%) cases. Histologically, the gallbladder wall was markedly thickened due to mucosal hyperplasia, inflammatory infiltrates, fibrosis, edema, hemorrhage, and smooth muscle hyperplasia\/hypertrophy. Twelve out of fourteen cases (85.7%) had concurrent cholecystitis of varying severity. Bacteria were detected by Giemsa or Warthin\u2013Starry stain in 8\/14 (57.1%) cases. Bacterial rods immunoreactive to the anti-Helicobacter antibody were present in one case. Mucosal epithelial cells of the gallbladder erosion\/ulcer cohort were immunopositive for the cyclooxygenases COX-1 or COX-2 in only 5\/14 (35.7%) cases. In contrast, COX-1 and COX-2 were more frequently expressed in a reference pool of cases of gallbladder mucocele (n = 5) and chronic cholecystitis (n = 5). COX-1 was expressed in 9\/10 cases (90.0%) of gallbladder mucocele and chronic cholecystitis and in 10\/10 cases (100%) for COX-2. (4) Conclusions: Canine gallbladder erosion\/ulcer is an under-reported condition which requires active clinical intervention. Based on the clinicopathological information reported in this study in addition to the COX-1 and COX-2 IHC results, we suggest that canine gallbladder erosion\/ulcer may be related to decreased cytoprotection physiologically provided by arachidonic acid, but which is decreased or absent due to reduced COX expression because of yet undetermined etiologies.<\/jats:p>","DOI":"10.3390\/ani13213335","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T09:56:36Z","timestamp":1698400596000},"page":"3335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Canine Gallbladder Erosion\/Ulcer and Hemocholecyst: Clinicopathological Characteristics of 14 Cases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6108-0097","authenticated-orcid":false,"given":"Ikki","family":"Mitsui","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Anatomy, Faculty of Veterinary Medicine, Okayama University of Science, Imabari 794-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Uchida","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dooley, J.S., Lok, A.S.F., Garcia-Tsao, G., and Pinzani, M. (2018). Sherlock\u2019s Diseases of the Liver and Biliary System, John Wiley & Sons, Inc.. [13th ed.].","DOI":"10.1002\/9781119237662"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1007\/BF01296665","article-title":"Fluid secretion by gallbladder mucosa in experimental cholecystitis is influenced by intramural nerves","volume":"32","author":"Thornell","year":"1987","journal-title":"Dig. Dis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.5326\/JAAHA-MS-7000","article-title":"Cholelithiasis in the Dog: Prevalence, Clinical Presentation, and Outcome","volume":"56","author":"Ward","year":"2020","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/jvim.14866","article-title":"Cholangitis and Cholangiohepatitis in Dogs: A Descriptive Study of 54 Cases Based on Histopathologic Diagnosis (2004\u20132014)","volume":"32","author":"Harrison","year":"2018","journal-title":"J. Vet. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2460\/javma.234.3.359","article-title":"Clinical, ultrasonographic, and laboratory findings associated with gallbladder disease and rupture in dogs: 45 cases (1997\u20132007)","volume":"234","author":"Crews","year":"2009","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_6","unstructured":"Maxie, M.G. (2016). Jubb, Kennedy, and Palmer\u2019s Pathology of Domestic Animals, Elsevier Inc.. [6th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1111\/jvim.13649","article-title":"Association of Gallbladder Mucocele Histologic Diagnosis with Selected Drug Use in Dogs: A Matched Case-Control Study","volume":"29","author":"Gookin","year":"2015","journal-title":"J. Vet. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gookin, J.L., Mathews, K.G., Cullen, J., and Seiler, G. (2018). Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191076"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kesimer, M., Cullen, J., Cao, R., Radicioni, G., Mathews, K.G., Seiler, G., and Gookin, J.L. (2015). Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138988"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"982","DOI":"10.2460\/javma.246.9.982","article-title":"Characterization, treatment, and outcome of bacterial cholecystitis and bactibilia in dogs","volume":"246","author":"Lawrence","year":"2015","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mitsui, I., Ohtsuki, S., and Uchida, K. (2021). Chronic Cholecystitis of Dogs: Clinicopathologic Features and Relationship with Liver. Animals, 11.","DOI":"10.3390\/ani11113324"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2460\/javma.2004.224.1615","article-title":"Gallbladder mucocele in dogs: 30 cases (2000\u20132002)","volume":"224","author":"Pike","year":"2004","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/vec.12910","article-title":"Prevalence and impact of cholecystitis on outcome in dogs with gallbladder mucocele","volume":"30","author":"Rogers","year":"2020","journal-title":"J. Vet. Emerg. Crit. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/jsap.13302","article-title":"Clinical characteristics and histology of cholecystectomised dogs with nongravity-dependent biliary sludge: 16 cases (2014\u20132019)","volume":"62","author":"Viljoen","year":"2021","journal-title":"J Small Anim. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.7326\/0003-4819-55-6-1008","article-title":"Hemocholecyst: A neglected cause of gastrointestinal hemorrhage","volume":"55","author":"Fitzpatrick","year":"1961","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11894-010-0092-5","article-title":"Hemobilia","volume":"12","author":"Chin","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1111\/j.1939-1676.2008.0156.x","article-title":"Acute hemobilia and hemocholecyst in 2 dogs with gallbladder carcinoid","volume":"22","author":"Lippo","year":"2008","journal-title":"J. Vet. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1354\/vp.41-4-416","article-title":"Canine gallbladder infarction: 12 cases (1993\u20132003)","volume":"41","author":"Holt","year":"2004","journal-title":"Vet. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1001\/archsurg.2009.265","article-title":"Hemorrhagic cholecystitis","volume":"145","author":"Parekh","year":"2010","journal-title":"Arch. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"rjy360","DOI":"10.1093\/jscr\/rjy360","article-title":"Literature review and case series of haemorrhagic cholecystitis","volume":"2019","author":"Tarazi","year":"2019","journal-title":"J. Surg. Case Rep."},{"key":"ref_21","first-page":"e22546","article-title":"A Rare Case of Acute Pancreatitis in the Setting of Hemorrhagic Cholecystitis","volume":"14","author":"Yap","year":"2022","journal-title":"Cureus"},{"key":"ref_22","unstructured":"Odze, R.D., and Goldblum, J.R. (2015). Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas, Elsevier Inc.. [3rd ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1748-1716.1988.tb08364.x","article-title":"Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat","volume":"132","author":"Thune","year":"1988","journal-title":"Acta Physiol. Scand."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1023\/A:1022832608466","article-title":"Cyclooxygenase-2 mediates mucin secretion from epithelial cells of lipopolysaccharide-treated canine gallbladder","volume":"48","author":"Kim","year":"2003","journal-title":"Dig. Dis. Sci."},{"key":"ref_25","first-page":"G998","article-title":"PGE generates intracellular cAMP and accelerates mucin secretion by cultured dog gallbladder epithelial cells","volume":"267","author":"Kuver","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1091-255X(98)80022-X","article-title":"Role of cyclooxygenase-2 for fluid secretion by the inflamed gallbladder mucosa","volume":"2","author":"Nilsson","year":"1998","journal-title":"J. Gastrointest. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3109\/00365528509088870","article-title":"The effects of morphine and enkephaline on gallbladder function in experimental cholecystitis. Inhibition of inflammatory gallbladder secretion","volume":"20","author":"Thornell","year":"1985","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1054\/plef.1999.0011","article-title":"Synthetic pathways of gallbladder mucosal prostanoids: The role of cyclooxygenase-1 and 2","volume":"60","author":"Longo","year":"1999","journal-title":"Prostaglandins Leukot Essent Fat. Acids"},{"key":"ref_29","unstructured":"Kumar, V., Abbas, A.K., and Aster, J.C. (2021). Robbins & Cotran Pathologic Basis of Disease, Elsevier Inc.. [10th ed.]."},{"key":"ref_30","first-page":"103615","article-title":"IgG4-related cholecystitis misinterpreted as gallbladder cancer, a case report","volume":"77","author":"Nazar","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_31","first-page":"e5393","article-title":"Endosalpingiosis of the Gallbladder: A Unique Complication of Ruptured Ectopic Pregnancy","volume":"11","author":"Porter","year":"2019","journal-title":"Cureus"},{"key":"ref_32","unstructured":"(2023, April 05). Share of Pet Dogs Castrated or Spayed in Japan as of October 2022. Statista. Available online: https:\/\/www.statista.com\/statistics\/1252986\/japan-pet-dogs-neutering-ratio\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/jvim.13974","article-title":"Bacterial Cholangitis, Cholecystitis, or both in Dogs","volume":"30","author":"Tamborini","year":"2016","journal-title":"J. Vet. Intern. Med."},{"key":"ref_34","unstructured":"Ettinger, S.J., Feldman, E.C. (2017). Textbook of Veterinary Internal Medicine, Elsevier Inc.. [8th ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dooley, J.S., Lok, A.S.F., Garcia-Tsao, G., and Pinzani, M. (2018). Sherlock\u2019s Diseases of the Liver and Biliary System, John Wiley & Sons, Inc.. [13th ed.].","DOI":"10.1002\/9781119237662"},{"key":"ref_36","first-page":"e21368","article-title":"Necrotizing Cholecystitis in the Gallbladder: A Case Report","volume":"14","author":"Katta","year":"2022","journal-title":"Cureus"},{"key":"ref_37","unstructured":"Jones, M.W., Gnanapandithan, K., Panneerselvam, D., and Ferguson, T. (2023, April 05). Chronic Cholecystitis, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470236\/."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2460\/ajvr.78.2.223","article-title":"Bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge","volume":"78","author":"Kakimoto","year":"2017","journal-title":"Am. J. Vet. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1292\/jvms.16-0562","article-title":"Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles","volume":"79","author":"Mizutani","year":"2017","journal-title":"J. Vet. Med. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e12457","DOI":"10.1111\/hel.12457","article-title":"Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta-analysis","volume":"23","author":"Cen","year":"2018","journal-title":"Helicobacter"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhou, D., Guan, W.B., Wang, J.D., Zhang, Y., Gong, W., and Quan, Z.W. (2013). A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070265"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/BF02389534","article-title":"Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa","volume":"31","author":"Kawaguchi","year":"1996","journal-title":"J. Gastroenterol."},{"key":"ref_43","first-page":"EC01","article-title":"Helicobacter pylori in Cholecystectomy Specimens-Morphological and Immunohistochemical Assessment","volume":"10","author":"Patnayak","year":"2016","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13099-015-0057-1","article-title":"Presence and significance of Helicobacter spp. in the gastric mucosa of Portuguese dogs","volume":"7","author":"Amorim","year":"2015","journal-title":"Gut Pathog."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4142\/jvs.2007.8.2.139","article-title":"Diagnosis of Helicobacter spp. infection in canine stomach","volume":"8","author":"Prachasilpchai","year":"2007","journal-title":"J. Vet. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/0300985821996657","article-title":"Alteration of Colonic Mucin Composition and Cytokine Expression in Acute Swine Dysentery","volume":"58","author":"Lin","year":"2021","journal-title":"Vet. Pathol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/21\/3335\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:12:25Z","timestamp":1760130745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/13\/21\/3335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ani13213335"],"URL":"https:\/\/doi.org\/10.3390\/ani13213335","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]}}}