Can Chromoendoscopy Improve the Early Diagnosis of Gastric Carcinoma in Dogs?

Chromoendoscopy has improved the early diagnosis of gastric cancer in humans but its usefulness in dogs is unknown. This study aimed at assessing whether adding narrow band imaging (NBI) or indigo carmine (IC) chromoendoscopy (CE) can improve the diagnostic yield of standard white light endoscopy (WLE). We compared the real-time findings of canine WLE, NBI-CE, and IC-CE and corresponding histology reports with endoscopic mucosal pattern assessment templates used in human medicine. Belgian Shepherd dogs are predisposed to gastric carcinoma. Therefore, 30 dogs of this breed served as the study population. According to histology, 17/30 dogs had mucosal changes (mucous metaplasia, glandular dysplasia, and gastric carcinoma). Diagnostic yield was best when targeted biopsies were taken with WLE and NBI-CE combined (15/17 cases). WLE alone positively identified only 8/17 cases and missed a gastric carcinoma in 3/6 cases. CE assessment templates based on macroscopic mucosal patterns, broadly used in human medicine, were not readily applicable in dogs. In conclusion, the study provides evidence that using CE in dogs has the potential to improve the diagnosis of precancerous gastric mucosal pathology and early gastric carcinoma. However, current image assessment templates from human medicine need major adjustments to the patterns of canine gastric mucosa.

Gastric mucosal pathology in Belgian Shepherd dogs with and without clinical signs of gastric disease.

BACKGROUND: Gastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations. RESULTS: The online survey included 232 responses. Logistic regression analysis recognized an association of vomiting with gagging, poor appetite and change in attitude. Recruitment for endoscopy included 16 BSD in Group A (mean age 9.1 ± 1.8 years, mean CCECAI = 3.1 ± 2.2 and signs of GER); and 11 in Group B (mean age 9.8 ± 1.4 years, CCECAI = 0, no signs of GER). Seven (25.9%) of the 27 BSD (Group A 4/16, Group B 3/11) had leukopenia. Serum C-reactive protein tended to be increased with more advanced GC (P = 0.063). Frequency of GC, mucosal atrophy, mucous metaplasia, or glandular dysplasia did not differ between groups. GC was frequently diagnosed (6/27), even without clinical signs (2/11). The odds ratio for vomiting (OR = 9.9; P = 0.016) was increased only when glandular dysplasia was present. GC was associated with mucous metaplasia (P = 0.024) and glandular dysplasia (P = 0.006), but not with mucosal atrophy (P = 1). CONCLUSIONS: GC can develop as an occult disease, associated with metaplasia and dysplasia of the gastric mucosa. Suggestive clinical signs, notably vomiting, should warrant timely endoscopy in BSD. Extensive endoscopic screening of asymptomatic dogs remains, however, unrealistic. Therefore, biomarkers of mucosal pathology preceding clinical illness are needed to support an indication for endoscopy and enable early diagnosis of GC.

Correction to: Canine breeds associated with gastric carcinoma, metaplasia and dysplasia diagnosed by histopathology of endoscopic biopsy samples.

An amendment to this paper has been published and can be accessed via the original article.

Canine breeds associated with gastric carcinoma, metaplasia and dysplasia diagnosed by histopathology of endoscopic biopsy samples.

BACKGROUND: Gastric carcinoma (GC) is a rather rare pathological finding in dogs, with the exception of some breeds which seem predisposed. The etiopathogenesis is largely unknown in dogs, whereas in humans GC often develops from gastric mucosal metaplasia and dysplasia. This study investigates whether dogs of certain breeds are more often subject to gastroduodenoscopy (GDS), and diagnosed with GC, mucosal metaplasia or dysplasia. A retrospective clinical database search was performed at the Veterinary Teaching Hospital at the University of Helsinki, Finland. The following inclusion criteria were applied to estimate relative risk for metaplasia/dysplasia and GC: dogs from pure breeds with at least five individuals subject to GDS with histopathology of gastric biopsies. RESULTS: Between 2006 and 2016, from a total of 54945 canine patients presented, 423 dogs underwent GDS. Inclusion criteria were met in 180 dogs of 20 different pure breeds. Eight dogs had GCs (mean age = 9.8 ± 1.7 years): Belgian Tervuren (n = 4), Collie (n = 2), Golden Retriever (n = 1) and Jack Russel Terrier (n = 1). Fourteen dogs of eight breeds had gastric mucosal metaplasia or dysplasia. A log-binomial statistical model revealed that dogs in the following breeds had a significantly higher probability to undergo GDS than the others in the study population: Australian Terrier, Belgian Tervuren, Cairn Terrier, Collie and Siberian Husky. Belgian Tervuren was found at higher risk to be diagnosed with GC [RR = 19 (5.7-63.9; P < 0.0001)], as well as mucosal metaplasia/dysplasia [RR (7.6; 2.95-19.58; P < 0.0001)], as compared to the other breeds included. Shetland Sheepdog had an increased RR (5.83; 1.75-19.45; P = 0.0041) for metaplasia. CONCLUSIONS: The results indicate a very low incidence of GC in dogs. The Belgian Tervuren, however, appears as predisposed. The histopathologic descriptions of mucosal changes such as metaplasia and dysplasia were also rare, but were more frequent in the Belgian Tervuren. Previous reports of these changes in dogs are very scarce, but they might be presumably related to GC in dogs, as they are in humans. Future research should investigate the possible role of metaplasia and dysplasia in the development of GC in dogs, especially those of predisposed breeds.

Basal Autophagy Is Altered in Lagotto Romagnolo Dogs with an ATG4D Mutation.

A missense variant in the autophagy-related ATG4D-gene has been associated with a progressive degenerative neurological disease in Lagotto Romagnolo (LR) dogs. In addition to neural lesions, affected dogs show an extraneural histopathological phenotype characterized by severe cytoplasmic vacuolization, a finding not previously linked with disturbed autophagy in animals. Here we aimed at testing the hypothesis that autophagy is altered in the affected dogs, at reporting the histopathology of extraneural tissues and at excluding lysosomal storage diseases. Basal and starvation-induced autophagy were monitored by Western blotting and immunofluorescence of microtubule associated protein 1A/B light chain3 (LC3) in fibroblasts from 2 affected dogs. The extraneural findings of 9 euthanized LRs and skin biopsies from 4 living affected LRs were examined by light microscopy, electron microscopy, and immunohistochemistry (IHC), using antibodies against autophagosomal membranes (LC3), autophagic cargo (p62), and lysosomal membranes (LAMP2). Biochemical screening of urine and fibroblasts of 2 affected dogs was performed. Under basal conditions, the affected fibroblasts contained significantly more LC3-II and LC3-positive vesicles than did the controls. Morphologically, several cells, including serous secretory epithelium, endothelial cells, pericytes, plasma cells, and macrophages, contained cytoplasmic vacuoles with an ultrastructure resembling enlarged amphisomes, endosomes, or multivesicular bodies. IHC showed strong membranous LAMP2 positivity only in sweat glands. The results show that basal but not induced autophagy is altered in affected fibroblasts. The ultrastructure of affected cells is compatible with altered autophagic and endo-lysosomal vesicular traffic. The findings in this spontaneous disease provide insight into possible tissue-specific roles of basal autophagy.

Infection with Possible Novel Parapoxvirus in Horse, Finland, 2013.

A horse in Finland exhibited generalized granulomatous inflammation and severe proliferative dermatitis. After euthanization, we detected poxvirus DNA from a skin lesion sample. The virus sequence grouped with parapoxviruses, closely resembling a novel poxvirus detected in humans in the United States after horse contact. Our findings indicate horses may be a reservoir for zoonotic parapoxvirus.

A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease.

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10-136) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to the macroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.