Persistent regurgitation in four dogs with caudal esophageal neoplasia.

Esophageal neoplasia is an uncommon, but important, consideration for acute and chronic regurgitation and megaesophagus in dogs. The diagnosis can be challenging, and treatment options are often limited. This case series describes four dogs with regurgitation secondary to caudal esophageal masses. All dogs presented with regurgitation, and three of the four dogs had radiographically apparent megaesophagus. In all dogs, ancillary diagnostics revealed the presence of a caudal esophageal mass resulting in esophageal obstruction, and all mass lesions were histopathologically confirmed to be neoplastic. Treatment responses were variable, with one dog still alive 37 mo postdiagnosis at the time of manuscript preparation.

Serum pancreatic lipase immunoreactivity in sick dogs after chronic administration of supraphysiologic doses of glucocorticoids.

BACKGROUND: Glucocorticoids (GC) are commonly used for a long term to treat a multitude of immune-mediated, inflammatory, and neoplastic diseases in dogs. Conflicting results of published studies on the effects of exogenous and endogenous GCs on serum canine pancreatic lipase immunoreactivity (cPLI) raise the question of whether cPLI concentrations can be reliably interpreted in patients receiving GCs. OBJECTIVE: We sought to determine the effect of long-term GC administration at supraphysiologic doses on serum cPLI concentrations in sick dogs. METHODS: Serum samples were collected from 35 client-owned dogs. Dogs were administered prednisone at a dose of ≥0.5 mg/kg per day for ≥3 weeks. Serum cPLI was measured prior to the initiation and after ≥3 weeks of GC therapy. RESULTS: There was a significant increase in serum cPLI between baseline (median 101 µg/L; range 30-1997 µg/L) and following the administration of ≥0.5 mg/kg/day of prednisone (median 173 µg/L; range 30-2000 µg/L) in dogs (P = 0.025). However, the median change was small (31 µg/L). There was no suspicion of pancreatitis in any of the dogs. Diagnostic interpretation changed in 6/35 dogs, with no apparent dose-response relationship. CONCLUSIONS: There was a statistically significant difference from baseline in serum cPLI measurements in sick dogs receiving long-term prednisone. Although the change was small and often clinically insignificant, it could pose a clinical interpretation dilemma in some dogs. It is unknown whether these observations are coincidental due to subclinical pancreatitis or caused by another effect of GCs on pancreatic acinar cells.

Genomic landscapes of canine splenic angiosarcoma (hemangiosarcoma) contain extensive heterogeneity within and between patients.

Cancer genomic heterogeneity presents significant challenges for understanding oncogenic processes and for cancer's clinical management. Variation in driver mutation frequency between patients with the same tumor type as well as within an individual patients' cancer can shape the use of mutations as diagnostic, prognostic, and predictive biomarkers. We have characterized genomic heterogeneity between and within canine splenic hemangiosarcoma (HSA), a common naturally occurring cancer in pet dogs that is similar to human angiosarcoma (AS). HSA is a clinically, physiologically, and genomically complex canine cancer that may serve as a valuable model for understanding the origin and clinical impact of cancer heterogeneity. We conducted a prospective collection of 52 splenic masses from 43 dogs (27 HSA, 15 benign masses, and 1 stromal sarcoma) presenting for emergency care with hemoperitoneum secondary to a ruptured splenic mass. Multi-platform genomic analysis included matched tumor/normal targeted sequencing panel and exome sequencing. We found candidate somatic cancer driver mutations in 14/27 (52%) HSAs. Among recurrent candidate driver mutations, TP53 was most commonly mutated (30%) followed by PIK3CA (15%), AKT1 (11%), and CDKN2AIP (11%). We also identified significant intratumoral genomic heterogeneity, consistent with a branched evolution model, through multi-region exome sequencing of three distinct tumor regions from selected primary splenic tumors. These data provide new perspectives on the genomic landscape of this veterinary cancer and suggest a cross-species value for using HSA in pet dogs as a naturally occurring model of intratumoral heterogeneity.

Comprehensive comparison of upper and lower endoscopic small intestinal biopsy in cats with chronic enteropathy.

BACKGROUND: Integrating immunohistochemistry (IHC) and clonality testing with histopathology may improve the ability to differentiate inflammatory bowel disease (IBD) and alimentary small cell lymphoma (LSA) in cats. HYPOTHESIS/OBJECTIVES: To evaluate the utility of histopathology, IHC, and clonality testing to differentiate between IBD and LSA and agreement of diagnostic results for endoscopic biopsy (EB) samples from the upper (USI) and lower small intestine (LSI). ANIMALS: Fifty-seven cats with IBD or LSA. METHODS: All cases were categorized as definitive IBD (DefIBD), possible LSA (PossLSA), probable LSA (ProbLSA), or definitive LSA (DefLSA) based on histopathology alone. Results from IHC and clonality testing were integrated. RESULTS: Based on histopathology alone, 24/57 (42.1%), 15/57 (26.3%), and 18/57 (31.6%) cats were diagnosed with DefIBD, PossLSA or ProbLSA, and DefLSA, respectively. After integrating IHC and clonality testing, 11/24 cases (45.8%) and 15/15 cases (100%) previously categorized as DefIBD and PossLSA or ProbLSA, respectively, were reclassified as LSA. A final diagnosis of IBD and LSA was reported in 13/57 (22.8%) and 44/57 (77.2%) cats, respectively. Agreement between USI and LSI samples was moderate based on histopathology alone (κ = 0.66) and after integrating IHC and clonality testing (κ = 0.70). However, only 1/44 (2.3%) of the LSA cases was diagnosed based on LSI biopsy alone. CONCLUSIONS AND CLINICAL IMPORTANCE: Integrating IHC and clonality testing increased the number of cases diagnosed with LSA, but the consequence for patient outcome is unclear. There was moderate agreement between USI and LSI samples. Samples from the LSI rarely changed the diagnosis.

Effects of storage and leukocyte reduction on the concentration and procoagulant activity of extracellular vesicles in canine packed red cells.

OBJECTIVES: To characterize the size and procoagulant activity of extracellular vesicles (EV) that accumulate in canine packed red blood cells (pRBCs) over time and the effect of leukocyte reduction on these characteristics. DESIGN: Prospective cohort study. SETTING: Private small animal specialty referral hospital and university research laboratories. ANIMALS: Ten healthy blood donor dogs. INTERVENTIONS: Five pRBCs units were obtained according to standard protocols, and 5 were leukocyte-reduced prior to processing. Platelet-free supernatant from the pRBC units was collected on days 0, 10, 20, 32, and 42. MEASUREMENTS AND MAIN RESULTS: Nanoparticle tracking analysis was performed to determine the size and concentration of EVs. Thrombin generation associated with phosphatidylserine-positive EVs was determined using a capture assay. Factor Xa generation associated with phosphatidylserine-positive EVs and tissue factor-positive EVs was measured in a subset of EVs isolated by centrifugation of the supernatant at 20,000 × g. R package nparLD and the Mann-Whitney U-test were used to determine the effect of duration of storage and the effect of leukocyte reduction, respectively. Small (mean < 125 nm) procoagulant EVs accumulated over time, with significant increases occurring on or after day 20 in both non-leukocyte reduced and leukocyte-reduced units. The procoagulant activity of the EVs was due to phosphatidylserine, not tissue factor. Increases in EV concentration and procoagulant activity occurred earlier in non-leukocyte reduced units. Extracellular vesicle accumulation and procoagulant activity were not decreased at any individual time point by leukocyte reduction. CONCLUSIONS: Further studies characterizing and determining the clinical relevance of small procoagulant EVs in pRBCs are warranted.

Polymerase chain reaction for antigen receptor rearrangement: Benchmarking performance of a lymphoid clonality assay in diverse canine sample types.

BACKGROUND: Polymerase chain reaction for antigen receptor rearrangement (PARR) is a molecular diagnostic tool used for discrimination of lymphoid malignancies in dogs from benign processes. Assay variations have been described and are commercially available, but performance metrics are not uniformly reported. OBJECTIVES: To describe performance (accuracy, sensitivity, specificity) and rigorous benchmarking of a PARR protocol (ePARR) in clinically relevant samples. ANIMALS: One hundred eighty-one client-owned dogs. METHODS: Lymphoma and benign tissues representative of the clinical spectrum with gold standard histopathologic and immunohistochemical diagnoses were collected. Assay development and benchmarking were performed on fresh frozen (FF) tissue, formalin-fixed paraffin-embedded (FFPE) tissue, flow cytometry pellets, and air-dried fine-needle aspirates (FNA). Assay performance was determined for FFPE from 56 dogs (18 B-cell lymphoma, 24 T-cell lymphoma, and 14 non-lymphoma), 80 frozen flow cytometry pellets (66 B-cell lymphoma, 14 T-cell lymphoma, 0 non-lymphoma), and 41 air-dried FNA slides (23 lymphoma, 18 non-lymphoma). RESULTS: For discrimination of lymphoma versus non-lymphoma, ePARR had 92% and 92% sensitivity and specificity on FFPE with 92% accuracy, 85% sensitivity from flow cytometry pellets (non-lymphoma was not evaluated to calculate specificity) with 85% accuracy, and 100% and 100% sensitivity and specificity for FNA with 100% accuracy. Stringent quality control criteria decreased assay success rate without significant performance improvement. Performance metrics were lower in most cases for discrimination of B- or T-cell versus non-B- or non-T-cell samples than for lymphoma versus non-lymphoma. CONCLUSIONS AND CLINICAL IMPORTANCE: These benchmarking data facilitate effective interpretation and application of PARR assays in multiple sample types.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs.

This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.

Transrectal stapling for colonic resection and anastomosis (10 cases).

The purpose of this retrospective study was to determine the feasibility of using the end-to-end anastomosis (EEA) stapling device transrectally for managing distal colonic disease in clinical veterinary cases. Ten animals met the criteria of having distal colonic or rectal resection and anastomosis with the EEA stapling device. The only complications seen after discharge from the hospital were colonic stricture at the anastomosis site in two animals and transient colitis in two animals. The stapled anastomosis has good success when properly applied, and the incidences of stricture formation, leakage, and other potential complications can be kept to a minimum.

Post-chemotherapy perforation in cats with discrete intermediate- or large-cell gastrointestinal lymphoma.

Objectives Gastrointestinal (GI) perforation is a well described complication of GI lymphoma in people, commonly occurring within days of initiation of chemotherapy. There are no studies documenting the prevalence of GI perforation in cats with intermediate- or large-cell GI lymphoma or whether it is associated with induction of chemotherapy. The objectives of this study were to document the prevalence and timing of post-chemotherapy perforation in cats with discrete GI masses caused by intermediate- or large-cell lymphoma. Methods Cats with a diagnosis of intermediate- or large-cell lymphoma based on cytologic or histopathologic examination of a mass lesion of the GI tract and treated with chemotherapy were identified by searching the patient record database of three large specialty referral hospitals. Cats undergoing surgical resection of a GI mass prior to chemotherapy were excluded from the study. A clinical diagnosis of GI perforation was made using ultrasound findings and analysis of abdominal fluid. Results Twenty-three cats with intermediate- (n = 3) or large-cell (n = 20) lymphoma were included in the study. GI perforation was confirmed in 4/23 cats (17%), and occurred at 23, 56, 59 and 87 days after induction. There was no association between tumor size, the presence of hypoproteinemia or suppurative inflammation within the mass at the time of diagnosis and subsequent perforation. Post-hoc analysis revealed that the magnitude of weight loss within 15-28 days of diagnosis was greater in cats with perforation. Conclusions and relevance In this pilot study, we found that post-chemotherapy GI perforation in cats with intermediate- or large-cell GI lymphoma occurs. Acute perforation after induction of chemotherapy was not documented. Larger prospective studies are needed to determine risk factors associated with perforation and whether surgical excision would reduce the risk of subsequent GI perforation in these patients.

Commentary on key aspects of fecal microbiota transplantation in small animal practice.

The gastrointestinal tract of dogs, cats, and other mammals including humans harbors millions of beneficial microorganisms that regulate and maintain health. Fecal microbiota transplantation (FMT) is a procedure involving the administration of a fecal infusion from a healthy individual (donor) to a patient with disease to help improve health. Despite the effectiveness of FMT to treat intestinal disorders in humans, in particular recurrent Clostridium difficile infection, there is a paucity of scientific data regarding the application of FMT in veterinary patients. Here, we outline key aspects of FMT in small animal practice.

Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs.

The objective of this study was to evaluate the safety and efficacy of a purified porcine insulin zinc suspension for treating dogs with uncomplicated diabetes mellitus. Fifty-three dogs were treated for 60 days after an initial dose determination period. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs were determined before beginning insulin therapy (time 0), at the end of the dose determination period (time 1), 30 days after time 1 (time 2), and 60 days after time 1 (time 3). Presence of polyuria, polydipsia, and ketonuria was determined at each time point. Adequacy of control of hyperglycemia was based on 12-hour blood glucose curves and improvement in clinical variables (results of physical examinations, historic information, polyuria, polydipsia, and ketonuria). Safety was evaluated by questionnaire, performance of physical examination, CBC, serum chemistry profile, and urinalysis. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs at times 1, 2, and 3 were significantly lower compared with time 0 (P < .0001). There was a reduction in the proportion of dogs with polyuria, polydipsia, and ketonuria of 82, 86, and 80%, respectively. All of the dogs had adequate glycemic control at time 1, 66% at time 2, and 75% at time 3. At time 3, 66% of dogs required insulin injections q12h. Other than hypoglycemia, there were no important adverse effects of insulin administration. The insulin, was safe and efficacious for reducing blood glucose and clinical signs in dogs with diabetes mellitus.

Exogenous thyrotoxicosis in dogs attributable to consumption of all-meat commercial dog food or treats containing excessive thyroid hormone: 14 cases (2008-2013).

OBJECTIVE: To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone. DESIGN: Retrospective and prospective case series. ANIMALS: 14 dogs. PROCEDURES: Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples. RESULTS: Total serum thyroxine concentrations were high (median, 8.8 µg/dL; range, 4.65 to 17.4 µg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 µg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 µg of thyroxine/g. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.

Feline gastrointestinal lymphoma.

Gastrointestinal lymphoma is a common cause of anorexia and weight loss in older cats, with or without vomiting or diarrhea. Most cats are feline leukemia virus-negative and feline immunodeficiency virus-negative. Low-grade gastrointestinal lymphoma may be more common than previously thought, and these cats respond better to chemotherapy agents than cats with high-grade lymphoma. The most significant prognostic indicator is initial response to chemotherapy, with cats that survive the initial induction period generally achieving long-term remission. Thus far, investigations into molecular markers and immunophenotyping have failed to identify useful prognostic indicators.

Seasonality of immune-mediated hemolytic anemia in dogs from southern California.

OBJECTIVE: To determine if there is seasonal variation in the incidence of canine idiopathic immune-mediated hemolytic anemia (IMHA) at 2 specialty hospitals in southern California. DESIGN: Retrospective study. To determine seasonality, cases of idiopathic IMHA presenting between June 2006 and June 2012 were identified by searching medical record databases of 2 large specialty hospitals. The presence of anemia with autoagglutination, spherocytosis or a positive Coomb's test and no identifiable underlying cause were required for inclusion. Dogs with a history of recent travel (within 1 year) were excluded. One hundred and twenty-six dogs, 57 from a practice in San Diego, and 69 from a practice in Los Angeles, met the criteria. RESULTS: The pattern of seasonality differed with practice location (P = 0.02). More cases of idiopathic IMHA presented during spring and summer (n = 39) than winter and fall (n = 18) for the San Diego practice (P = 0.008) but not the Los Angeles practice (n = 32 and 37, respectively, P = 0.63). CONCLUSIONS: The incidence of idiopathic IMHA in dogs presenting to specialty hospitals located in 2 different climates of southern California was different, suggesting environmental triggers may be involved. Larger, prospective studies are needed to determine whether environmental parameters or undetected infectious disease account for some cases of idiopathic IMHA in dogs.