Michael D. Willard

Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group.

The characterization of inflammatory change in endoscopic biopsy samples of the gastrointestinal mucosa is an increasingly important component in the diagnosis and management of canine and feline gastrointestinal disease. Interpretation has hitherto been limited by the lack of standard criteria that define morphological and inflammatory features, and the absence of such standardization has made it difficult, if not impossible, to compare results of retrospective or prospective studies. The World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group was established, in part, to develop endoscopic and microscopical standards in small animal gastroenterology. This monograph presents a standardized pictorial and textual template of the major histopathological changes that occur in inflammatory disease of the canine and feline gastric body, gastric antrum, duodenum and colon. Additionally, a series of standard histopathological reporting forms is proposed, to encourage evaluation of biopsy samples in a systematic fashion. The Standardization Group believes that the international acceptance of these standard templates will advance the study of gastrointestinal disease in individual small companion animals as well as investigations that compare populations of animals.

Clinicopathological abnormalities and treatment response in 24 dogs seroreactive to Bartonella vinsonii (berkhoffii) antigens.

Bartonella vinsonii (B. vinsonii) subspecies berkhoffii is a recently recognized cause of endocarditis, myocarditis, and granulomatous disease in dogs. In an effort to elucidate other potential disease manifestations, the case records of 24 dogs that were seroreactive to B. vinsonii (berkhoffii) antigens were studied retrospectively. Diagnoses included immune-mediated hemolytic anemia, neutrophilic or granulomatous meningoencephalitis, neutrophilic polyarthritis, cutaneous vasculitis, and uveitis. Repeated B. vinsonii (berkhoffii) antibody titers became negative after treatment. This study indicates that a diverse spectrum of disease manifestations and clinicopathological abnormalities can be detected in dogs that are seroreactive to B. vinsonii (berkhoffii) antigens.

Effect of Sample Quality on the Sensitivity of Endoscopic Biopsy for Detecting Gastric and Duodenal Lesions in Dogs and Cats

BACKGROUND The quality of histopathology slides of endoscopic biopsies from different laboratories varies, but the effect of biopsy quality on outcome is unknown. HYPOTHESIS The ability to demonstrate a histologic lesion in the stomach or duodenum of a dog or cat is affected by the quality of endoscopic biopsy samples submitted. More endoscopic samples are needed to find a lesion in poor-quality tissue specimens. ANIMALS Tissues from 99 dogs and 51 cats were examined as clinical cases at 8 veterinary institutions or practices in 5 countries. METHODS Histopathology slides from sequential cases that underwent endoscopic biopsy were submitted by participating institutions. Quality of the histologic section of tissue (inadequate, marginal, adequate), type of lesion (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity of different quality tissue samples for finding different lesions was determined. RESULTS Fewer samples were required from dogs for diagnosis as the quality of the sample improved from inadequate to marginal to adequate. Duodenal lesions in cats displayed the same trend except for moderate duodenal infiltrates for which quality of tissue sample made no difference. Gastric lesions in dogs and mild gastric lesions in cats had the same trend, whereas the number of tissue samples needed to diagnose moderately severe gastric lesions in cats was not affected by the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE The quality of endoscopically obtained tissue samples has a profound effect on their sensitivity for identifying certain lesions, and there are differences between biopsies of canine and feline tissues.

Comparison of histopathologic findings in biopsies from the duodenum and ileum of dogs with enteropathy.

BACKGROUND In the investigations of dogs with chronic small intestinal diarrhea collection of ileal biopsies lengthens procedural time and has been of uncertain value. OBJECTIVES To evaluate whether there was agreement between histologic changes present in samples of duodenal and ileal mucosa, and hence to provide initial information in the process of determining whether collection of ileal biopsies is clinically justified. ANIMALS 40 dogs with chronic small and large intestinal diarrhea from which endoscopic (in 30 cases) or surgical (in 10 cases) duodenal and ileal biopsies had been collected. METHODS Samples were reviewed concurrently by two observers (MJD and MDW) using the scoring system developed by the World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group. Comparisons were made by kappa analysis. RESULTS Microscopic pathology was observed in 30 cases. Only eight out of this 30 (27%) had the same histopathologic diagnosis in both the duodenum and the ileum. This dropped to 3 out of 30 (10%) if different disease severity was also considered as disagreement. Microscopic pathology would have been found in 60% and 80% of the 30 cases, if only duodenal or ileal biopsies respectively, had been available. CONCLUSIONS AND CLINICAL IMPORTANCE There was poor agreement between histopathological findings from duodenal versus ileal biopsies with abnormalities sometimes being more readily detected in the ileum. Routine collection of ileal plus duodenal samples appears warranted when concurrent small and large intestinal diarrhea is present.

Effect of Tissue Processing on Assessment of Endoscopic Intestinal Biopsies in Dogs and Cats

BACKGROUND Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. HYPOTHESIS Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. ANIMALS Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. METHODS Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while kappa statistics determined agreement between pathologists on histologic lesions. RESULTS There was poor agreement (kappa = -0.013 to 0.3) between pathologists, and institution of origin of slides had effect (kappa = 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum kappa = 0.69 using 4-point scale versus maximum kappa = 1.0 using 2-point scale). Significant association (P = .019- .04; 95% OR = 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.

Esophagitis and esophageal strictures

Esophagitis and esophageal strictures are important causes of esophageal disease in dogs and cats. Clinical suspicion is created when the clinician recognizes the clinical signs suggestive of esophageal disease and accounts for historical information and physical examination findings. Once suspected, the diagnosis of esophagitis and esophageal strictures is a fairly simple one in most cases. Although the benefit of diminishing secretion of gastric acid in patients with esophagitis is unquestioned, other questions regarding adjunctive medical treatments, such as sucralfate and glucocorticoids for dogs and cats with esophagitis, have not been answered through appropriate clinical studies. Esophageal strictures are readily treated with balloon dilation or esophageal bougienage, and clients can expect most patients to become functional, although dietary change may be necessary.

Utility of Endoscopic Biopsies of the Duodenum and Ileum for Diagnosis of Inflammatory Bowel Disease and Small Cell Lymphoma in Cats

BACKGROUND Endoscopic duodenal biopsies are relatively convenient, minimally invasive tests for infiltrative intestinal disorders of cats. Ileal endoscopic biopsies might not be performed because of technical difficulty and effort required to prepare the colon. It is not known whether or not histopathology of feline duodenal and ileal biopsies for detection of inflammatory bowel disease (IBD) and small cell lymphoma (SC-LSA) provides comparable results. OBJECTIVES To evaluate the agreement between endoscopic biopsies of duodenum and ileum in cats with IBD and SC-LSA. ANIMALS Seventy client-owned cats with gastrointestinal disease and adequate duodenal and ileal tissue biopsies obtained endoscopically. METHODS Retrospective study: Search of medical records of cats with enteropathy and endoscopy. Samples were blinded and re-evaluated by single pathologist (JM) for quality, number of biopsies, and diagnosis according to WSAVA standards. Agreement of IBD and SC-LSA diagnoses among biopsy sites assessed using Cohens Kappa. RESULTS Eighteen of 70 cats (26%) were diagnosed with SC-LSA in duodenum, ileum, or both. Of these 18 cats, 7 (39%) were diagnosed with only duodenal SC-LSA, 8 (44%) were diagnosed with only ileal SC-LSA, and 3 (17%) had SC-LSA in both duodenum and ileum. There was poor agreement on diagnosis between duodenal and ileal biopsies (kappa = 0.23). CONCLUSIONS AND CLINICAL IMPORTANCE Although review by a single pathologist remains a limitation of this study, results suggest that there is a population of cats in which diagnosis of SC-LSA can be found only by evaluation of ileal biopsies. Clinicians should consider performing both upper and lower GI endoscopic biopsies in cats with infiltrative small bowel disease.

Intestinal Crypt Lesions Associated with Protein‐Losing Enteropathy in the Dog

Six dogs were diagnosed with protein losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa.

Biopsy of the gastrointestinal tract

Gastrointestinal biopsy is a potentially powerful tool, but it is easy to do it incorrectly. If clinicians are careless in performing or submitting biopsies, or if they blindly believe whatever the histopathology report says, they are abdicating their responsibility to the client and patient. Two comments seem most appropriate. First, the goal of endoscopy is not to be able to place the tip of an endoscope in a particular location; rather, the goal of endoscopy is to be able to access a particular location and then take a diagnostic specimen well enough that surgery can be avoided. Second, attention to detail is worth at least as much if not more than technology.

Efficacy of omeprazole versus high-dose famotidine for prevention of exercise-induced gastritis in racing Alaskan sled dogs.

BACKGROUND Omeprazole and famotidine both reduce severity of exercise-induced gastritis, but administering famotidine is easier than administering omeprazole during racing competition. HYPOTHESIS Famotidine is more efficacious than no treatment in reducing severity of exercise-induced gastritis; and high-dose famotidine is more efficacious than omeprazole in reducing severity of exercise-induced gastritis. ANIMALS Experiment 1: Randomized placebo-controlled study, 36 sled dogs (3-8 years); Experiment 2: Randomized positive-control study, 52 sled dogs (2-8 years). METHODS Experiment 1: Equal numbers of dogs randomly assigned to famotidine (20 mg q24h) or no treatment groups. Gastroscopy was performed 24 hours after the dogs ran 330 miles. Mucosal appearance was blindly scored by previously described scoring system. Experiment 2: Equal numbers of dogs randomly assigned to omeprazole (20 mg q24h) or high-dose famotidine (40 mg q12h) groups. Gastroscopy was performed 48 hours before and 24 hours after the dogs ran 300 miles. Mucosal appearance was blindly scored by previously described scoring system. RESULTS Famotidine reduced the prevalence of clinically relevant, exercise-induced gastric lesions compared with no treatment (7/16 versus 11/16, P = .031). Compared with high-dose famotidine, omeprazole significantly decreased the severity (0.4 versus 1.2, P = .0002) and prevalence (2/23 versus 7/21, P = .049) of gastric lesions. CONCLUSIONS AND CLINICAL RELEVANCE Although famotidine provides some benefit in the prevention of exercise-induced gastric lesions, omeprazole is superior to famotidine in preventing gastritis in dogs running 300 miles. Routine administration of omeprazole is recommended to prevent stress-associated gastric disease in exercising and racing Alaskan sled dogs.