Ultrasonographic Evaluation of the Muscularis Propria in Cats with Diffuse Small Intestinal Lymphoma or Inflammatory Bowel Disease

Background: An ultrasonographic pattern of thickened muscularis propria in the small intestine and lymphadenopathy have been associated with gastrointestinal lymphoma and inflammatory bowel disease (IBD) in cats. Objectives: To investigate the association of these imaging biomarkers with IBD and lymphoma in cats. Animals: One hundred and forty‐two cats with a histologic diagnosis of normal small intestine (SI) (n = 56), lymphoma (n = 62), or IBD (n = 24). Methods: Retrospective case review. Pathology records from 1998–2006 were searched for cats with a diagnosis of normal, IBD, or lymphoma, an ultrasonographic examination <28 days before surgery, and without ultrasonographic evidence of a mass. Multinomial regression analysis was used to determine the association of imaging biomarkers with disease status. Results: Cats with thickening of the muscularis propria detected by ultrasonographic examination were more likely to have lymphoma compared with normal SI cats (odds ratio [OR] = 4.0, 95% confidence interval [95% CI] 1.2–13.1, P= .021) and those with IBD (OR = 18.8, 95% CI 2.2–162.7, P= .008). Histologic samples of cats with muscularis propria thickening were more likely to have disease infiltrates in both the mucosal and submucosal layers (OR = 8.1, 95% CI 1.7–38.4, P= .008) than cats with normal SI. Cats with ultrasonographic evidence of lymphadenopathy were more likely to have a diagnosis of lymphoma (OR = 44.9, 95% CI 5.1–393.0, P= .001) or IBD (OR = 10.8, 95% CI 1.1–106.3, P= .041) than normal SI. Fifty‐six of 62 cats had confirmed or presumptive diagnosis of diffuse T‐cell lymphoma. Conclusions and Clinical Relevance: Older cats with muscularis layer thickening are more likely to have T‐cell lymphoma than IBD. The ultrasonographic pattern is associated with histologic infiltrates in the mucosal and submucosal layers of small intestine. Lymphadenopathy is associated with lymphoma or IBD.     

Feline idiopathic inflammatory bowel disease: what we know and what remains to be unraveled

PRACTICAL RELEVANCE: Feline idiopathic inflammatory bowel disease (IBD) denotes one form of chronic enteropathy that is immunologically mediated and characterized by persistent or recurrent gastrointestinal (GI) signs and histologic inflammation. Signs of vomiting, diarrhea and weight loss generally predominate, and mucosal inflammation may occur in any portion of the GI tract (especially the small intestine). Affected cats may also have concurrent inflammation in other organs, such as the pancreas and liver, which may impact clinical disease severity. CLINICAL CHALLENGES: The exact etiologies of this heterogeneous group of disorders have yet to be determined, though results from basic science and clinical studies suggest that interplay between genetic factors and enteric bacteria is crucial for disease development. The diagnosis is one of exclusion and requires intestinal mucosal biopsy to characterize the type and severity of the inflammatory infiltrate, and to differentiate IBD from other disorders, including alimentary lymphoma. Controversy exists concerning the relative diagnostic accuracy of endoscopic versus full-thickness specimens for the diagnosis of IBD and its differentiation from alimentary lymphoma. AUDIENCE: This article is intended to provide veterinary practitioners with a comprehensive clinical update on idiopathic IBD in cats. It reviews the current evidence-based data, the diagnostic approach, the evolving histologic criteria, and treatment options and outcome for feline patients with this syndrome.     

Feline epitheliotropic intestinal malignant lymphoma: 10 cases (1997-2000)

The clinical, histopathologic, and immunohistochemical features of 10 cats with epitheliotropic intestinal malignant lymphoma (EIL) are described. Intestinal biopsy samples were reviewed by 3 pathologists to confirm the diagnosis of EIL. These samples (n = 10) were compared to the intestinal biopsies of normal cats (n = 11), cats with inflammatory bowel disease (IBD; n = 7), and cats with non-EIL (n = 9) for quantification and immunophenotyping of intraepithelial lymphocytes. Immunophenotypic studies were performed with CD3 and CD79a antibody stains to assess for T- and B-cell immunoreactivity, respectively. EIL biopsies had markedly more intraepithelial lymphocytes than normal intestine (NRL) and samples from cats with IBD. However, no marked difference was observed in the number of intraepithelial lymphocytes in cats with non-EIL compared to cats with EIL. Regardless of the histologic diagnosis, the intraepithelial lymphocytes in all cats were small- to intermediate-sized T cells. Clinical findings and imaging studies in the cats identified minimal or nonspecific findings in affected cats. Most cats fit the typical profile of cats with IBD or alimentary malignant lymphoma. Nine of 10 cats with EIL were treated with prednisone with or without additional chemotherapy. Four cats were refractory to chemotherapy and were euthanized within 3.5 months. The remaining 5 cats had long-term survival times of 11 months or greater. The median survival time was 11 months. Additional studies are warranted to better characterize EIL and its relationship to IBD in cats and non-EIL and to identify optimal treatment strategies for this disease.     

Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples

Differentiating between inflammatory bowel disease (IBD) and small intestinal lymphoma in cats is often difficult, especially when only endoscopic biopsy specimens are available for evaluation. However, a correct diagnosis is imperative for proper treatment and prognosis. A retrospective study was performed using surgical and endoscopic intestinal biopsy specimens from 63 cats with a history of chronic diarrhea or vomiting or weight loss. A diagnosis of lymphoma or inflammation was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone, HE-stained sections plus results of immunohistochemical labeling (IHC) for CD3e and CD79a, and HE staining, immunophenotyping, and polymerase chain reaction (PCR) results for B and/or T cell clonality. In addition, various histomorphologic parameters were evaluated for significant differences between lymphoma and IBD using Fisher's exact test. The sensitivity and specificity of each parameter in the diagnosis of lymphoma were also determined. Results of Bayesian statistical analysis demonstrated that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphoid infiltrates results in more accurate differentiation of neoplastic versus inflammatory lymphocytes. Important histologic features that differentiated intestinal lymphoma from IBD included lymphoid infiltration of the intestinal wall beyond the mucosa, epitheliotropism (especially intraepithelial nests and plaques), heterogeneity, and nuclear size of lymphocytes. Based on the results of this study, a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes, was developed to more accurately differentiate between intestinal lymphoma and IBD.     

Evaluation of lymphocyte apoptosis in dogs with inflammatory bowel disease

Objective-To determine whether lymphocyte apoptosis in intestinal mucosae is more common in healthy dogs than dogs with inflammatory bowel disease (IBD) and whether numbers of apoptotic cells increase after successful treatment of affected dogs. Animals-8 dogs with IBD (IBD dogs) and 8 healthy control dogs. Procedures-Biopsy specimens of the duodenum and colon were obtained via endoscopy from dogs with IBD before and after 10 weeks of standard treatment and compared with specimens obtained from control dogs. Expression of activated caspase 3 (Casp3), caspase-cleaved fragment p85 from poly-ADP-ribose polymerase (PARP), and B-cell leukemia/lymphoma 2 (Bcl-2) was measured in the duodenal (villous tip and base) and colonic mucosae. Results-Expression of Casp3 was greater in the duodenal villous tips of control dogs, compared with expression in similar tissues from dogs with IBD before or after treatment. Despite clinical improvement of dogs with IBD, expression of Casp3 did not increase after treatment. Expression of PARP did not differ between groups at any time point. Expression of Bcl-2 was greater at all 3 tissue sites in control dogs, compared with expression at the same sites in dogs with IBD. Furthermore, Bcl-2 expression in duodenal villous tips was higher in dogs with IBD after treatment but was not higher elsewhere. In control dogs, expression patterns for all 3 markers were similar between sites (villous tip > villous base > colon). Conclusions and Clinical Relevance-Expression of Casp3 in lymphocytes in duodenal villous tips was significantly reduced in dogs with IBD, compared with expression in healthy dogs, but no increase was detected following successful treatment of IBD. Increased expression of Bcl-2 may be a potential marker of the success of treatment.     

Subnormal concentrations of serum cobalamin (vitamin B12) in cats with gastrointestinal disease

The present study sought to determine the spectrum of diseases associated with subnormal concentrations of serum cobalamin in cats undergoing investigation of suspected gastrointestinal problems. The solid-phase boil radioassay (RA) for cobalamin employed in the present study was immunologically specific, precise, and accurate, with a sensitivity of 15 pg/mL. The RA yielded results that strongly correlated with those obtained by bioassay (Spearmann rho = .805; P < .0001), although the absolute values were lower for the RA. Forty-nine of 80 serum samples submitted during the period of January 1996-January 1998 had cobalamin concentrations below the reference range for healthy cats (range 900-2,800 pg/mL; mean +/- SD, 1,775 +/- 535 pg/mL; n = 33). Cats with subnormal cobalamin concentrations (mean +/- SD; 384 +/- 272 pg/mL, range 3-883 pg/mL) were middle-aged or older and were presented for weight loss. diarrhea, vomiting, anorexia, and thickened intestines. Definitive diagnoses in 22 cats included inflammatory bowel disease (IBD), intestinal lymphoma, cholangiohepatitis or cholangits, and pancreatic inflammation. Serum concentrations of cobalamin were particularly low in cats with intestinal lymphoma, three-fifths of whom also had subnormal serum concentrations of folate (< 9 ng/mL). The simultaneous presence of disease in the intestines, pancreas, or hepatobiliary system in many cats made it difficult to determine the cause of subnormal cobalamin concentrations. The circulating half-life of parenteral cyanocobalamin was shorter in 2 cats with IBD (5 days) than in 4 healthy cats (12.75 days). The presence of subnormal serum concentrations of cobalamin in 49 of 80 cats evaluated suggests that the measurement of serum cobalamin may be a useful indirect indicator of enteric or pancreatic disease in cats. The rapid depletion of circulating cobalamin in cats suggests that cats may be highly susceptible to cobalamin deficiency. However, the relationship of subnormal serum cobalamin concentrations to cobalamin deficiency and the effect of cobalamin deficiency on cats remain to be determined.     

Treatment of feline gastrointestinal small-cell lymphoma with chlorambucil and glucocorticoids

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease-all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.     

Quantitative assessment of mast cells and expression of IgE protein and mRNA for IgE and interleukin 4 in the gastrointestinal tract of healthy dogs and dogs with inflammatory bowel disease

OBJECTIVE: To characterize the mucosal IgE network in dogs affected with inflammatory bowel disease (IBD) and compare it with that for healthy dogs. ANIMALS: 9 healthy dogs and 20 dogs with IBD. PROCEDURE: In situ hybridization of mRNA specific for IgE and interleukin 4 (IL-4) and immunohistochemical analysis for IgE protein and 2 markers of mast cells (ie, tryptase and chymase) were performed on tissue sections obtained from the gastrointestinal (GI) tract and lymph nodes of dogs. RESULTS: Dogs with IBD had significantly more cells positive for IgE protein and more mast cells in the GI mucosa than healthy dogs. Despite this significant increase in number of cells positive for IgE, cells positive for IgE mRNA were rarely detected in the GI mucosa; most cells positive for IgE mRNA were found in mesenteric lymph nodes. Signal pattern of IL-4 mRNA was similar to that of IgE mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: The increased numbers of cells positive for IgE and mast cells in dogs with IBD suggest hypersensitivity such as hypersensitivity to bacterial or dietary-derived antigens in the intestinal lumen. Future studies need to elucidate whether this represents a cause of inflammation or is a result of the inflammatory process of IBD.     

Clinical characteristics and outcome in dogs with small cell T‐cell intestinal lymphoma

Small cell intestinal lymphoma has not been well characterized in dogs. The objective of this study was to describe clinical characteristics and outcome in dogs with small cell intestinal lymphoma. We hypothesized that affected dogs would have prolonged survival compared with high‐grade gastrointestinal (GI) lymphoma. Pathology records were searched for dogs with histologically confirmed small cell GI lymphoma. Seventeen dogs with confirmed small cell intestinal lymphoma were identified, and clinical and outcome data were retrospectively collected. Histopathology was reviewed by a board‐certified pathologist, and tissue sections were subjected to immunophenotyping and molecular clonality assessment. All dogs had small cell, T‐cell, lymphoma confirmed within various regions of small intestine, with 1 dog also having disease in abdominal lymph nodes. All dogs had clinical signs attributable to GI disease; diarrhoea (n = 13) was most common. Ultrasonographic abnormalities were present in 8 of 13 dogs with abnormal wall layering (n = 7) and hyperechoic mucosal striations (n = 7) representing the most common findings. In total, 14 dogs received some form of treatment. The median survival time (MST) for all dogs was 279 days and the MST for the 14 dogs that received any treatment was 628 days. Dogs with anaemia and weight loss at presentation had significantly shorter survival times and dogs that received a combination of steroids and an alkylating agent had significantly longer survival times. Small cell, T‐cell, intestinal lymphoma is a distinct disease process in dogs, and those undergoing treatment may experience prolonged survival.     

Radiographic, ultrasonographic, and endoscopic findings in cats with inflammatory bowel disease of the stomach and small intestine: 33 cases (1990-1997).

OBJECTIVE: To characterize imaging findings in cats with confirmed inflammatory bowel disease (IBD) of the upper gastrointestinal tract (i.e., stomach and small intestine) and relate these findings to clinical signs and histologic changes. DESIGN: Retrospective study. ANIMALS: 32 cats with clinical and histopathologic diagnoses of IBD. PROCEDURE: Medical records were reviewed for signalment, clinical signs, clinicopathologic findings, radiographic and ultrasonographic findings, and results of endoscopic examination. Histologic findings were reviewed and characterized by severity and type of inflammatory infiltrate. RESULTS: All cats had 1 or more clinical signs (e.g., vomiting, diarrhea, weight loss, and anorexia) consistent with IBD. Lymphocytic and plasmacytic infiltrates were observed in histologic sections of gastrointestinal tissue. Crypt distortion, villous blunting and fusion, and fibrosis were most commonly seen in cats with moderate or severe IBD. Clinicopathologic findings of some cats included anemia, leukocytosis or leukopenia, hypocholesterolemia, and hyper- or hypoproteinemia. Abnormalities were not found on abdominal radiographic views in 9 of 9 cats. However, contrast studies using barium revealed radiographic abnormalities in 1 of 3 cats. In 13 of 17 cats, abdominal ultrasonography revealed several intestinal abnormalities (e.g., poor intestinal wall layer definition, focal thickening) and large mesenteric lymph nodes with hypoechoic changes consistent with IBD. Endoscopic observation revealed findings (e.g., erythema, plaques, mucosal friability) consistent with inflammation in 9 of 18 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with endoscopy of the gastrointestinal tract or abdominal radiography, clinical signs and ultrasonographic findings appear to have the best association with histologic grade of IBD in cats.     

A retrospective evaluation of lomustine (CeeNU) in 32 treatment naïve cats with intermediate to large cell gastrointestinal lymphoma (2006–2013)

Multi‐drug chemotherapy protocols for feline lymphoma have demonstrated variable efficacy and tolerability. In phase I trials, lomustine has demonstrated efficacy for cats with lymphoma though its use for treatment naïve feline intermediate/large cell gastrointestinal (GI) lymphoma remains unknown. This study evaluated the efficacy and tolerability of lomustine for the treatment of feline GI lymphoma. Thirty‐two cats with histologically or cytologically confirmed intermediate/large cell GI lymphoma were evaluated retrospectively. Factors assessed included clinical signs, hematologic/biochemical parameters and use of l ‐asparaginase at induction. A response rate of 50% (16/32), with median duration of response of 302 days (range 64–1450 days), was found. Median progression‐free interval was 132 days (range 31–1450 days), with overall median survival time of 108 days (range 4–1488 days). History of hyporexia, presence of anaemia and dose of lomustine were significantly associated with progression‐free survival. Overall, lomustine is a well‐tolerated and effective treatment for feline GI lymphoma.     

A Clinical Index for Disease Activity in Cats with Chronic Enteropathy

Background: There is a need for a clinically useful, quantitative index for measurement of disease activity in cats with chronic enteropathy (CE). Objective: To develop a numerical activity index that is of practical value to clinicians treating CE in cats. Animals: Eighty‐two cats with CE. Methods: Retrospective case review of 59 cats diagnosed with inflammatory bowel disease (IBD). Prospective validation study of 23 cats having either IBD or food‐responsive enteropathy (FRE). Multivariate regression analysis was used to identify which combination of clinical and laboratory variables were best associated with intestinal inflammation of IBD. This combination of variables was expressed in a score that was used as an activity index for the prospective assessment of disease activity and of the effect of treatment in cats with IBD or FRE. Results: The combination of gastrointestinal signs, endoscopic abnormalities, serum total protein, serum alanine transaminase/alkaline phosphatase activity, and serum phosphorous concentration had the best correlation with histopathologic inflammation and comprise the feline chronic enteropathy activity index (FCEAI). Positive treatment responses in cats with CE were accompanied by significant (P < .05) reductions in FCEAI scores after treatment. Conclusions and Clinical Importance: The FCEAI is a simple numerical measure of inflammatory activity in cats with CE. The scoring index can be reliably used in the initial assessment of disease severity for both IBD and FRE and as a measure of clinical response to treatment for these disorders.     

Structural and functional changes of neuronal and glial components of the feline enteric nervous system in cats with chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract

Immunohistochemical examinations of the enteric nervous system (ENS) were performed on biopsies of healthy cats and compared to findings in cats suffering from inflammatory bowel disease or intestinal lymphoma. In lymphocytic–plasmacytic enterocolitis all affected samples had significant reductions in glial fibrillary acidic protein and vasoactive intestinal peptide (VIP) and mostly of neuron-specific enolase (NSE) possibly reflecting alterations in enteric glial cells and neurons. In cases with eosinophilic gastroenterocolitis significantly reduced phosphorylated neurofilament (PN) expression was present suggesting a disturbance in neuronal cytoskeleton, whereas cats with fibrosing enteropathy had reduced expression of NSE, non-phosphorylated neurofilaments (NPN), PN and VIP, possibly reflecting neuronal disturbances. In cases with intestinal lymphoma only the reduction in PN and the increase in NPN were obvious suggesting direct damage or interference of neoplastic cells with enteric neurons. In conclusion, structural and functional alterations of the ENS may contribute to clinically evident signs of vomiting and/or diarrhea.     

Structural and functional changes of neuronal and glial components of the feline enteric nervous system in cats with chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract

Immunohistochemical examinations of the enteric nervous system (ENS) were performed on biopsies of healthy cats and compared to findings in cats suffering from inflammatory bowel disease or intestinal lymphoma. In lymphocytic–plasmacytic enterocolitis all affected samples had significant reductions in glial fibrillary acidic protein and vasoactive intestinal peptide (VIP) and mostly of neuron-specific enolase (NSE) possibly reflecting alterations in enteric glial cells and neurons. In cases with eosinophilic gastroenterocolitis significantly reduced phosphorylated neurofilament (PN) expression was present suggesting a disturbance in neuronal cytoskeleton, whereas cats with fibrosing enteropathy had reduced expression of NSE, non-phosphorylated neurofilaments (NPN), PN and VIP, possibly reflecting neuronal disturbances. In cases with intestinal lymphoma only the reduction in PN and the increase in NPN were obvious suggesting direct damage or interference of neoplastic cells with enteric neurons. In conclusion, structural and functional alterations of the ENS may contribute to clinically evident signs of vomiting and/or diarrhea.     

Immune cell populations in the duodenal mucosa of cats with inflammatory bowel disease

The aim of this study was to characterize the phenotype of leukocytes infiltrating the duodenal mucosa of cats with inflammatory bowel disease (IBD) by using immunohistochemistry and computer-aided morphometry to assess whether immunologic markers would aid in characterization of IBD. Frozen and formalin-fixed duodenal biopsies were collected from cats referred for investigation of chronic vomiting, diarrhea, or both (n = 34). Reference ranges were previously established by using duodenal samples from healthy cats (n = 16). No significant difference was found in the number of immunoglobulin G+ (IgG+) or IgA+ in either the villous lamina propria or the crypt lamina propria between cats with IBD and control cats. T cells (CD3+) increased in number from crypt to the tip of the villi in biopsies from both diseased (mean +/- SD for each group was 18.8 +/- 6.6 and 17.7 +/- 4.2 cells/ 10,000 m2 in cryptal areas to 25.2 +/- 9.5 and 29.1 +/- 13.3 cells/10,000m2 in villous areas) and healthy animals (17.9 +/- 3.9 cells/10,000 microm2 in cryptal areas to 24.1 +/- 9.3 cells/10,000 microm2 in villous areas) and no significant difference was found between diseased and control cats. By contrast, major histocompatibility complex (MHC) class II expression by leukocytes with dendritic cell or macrophage morphology in the lamina propria was significantly greater in cats with IBD (13.3 +/- 4.2 cells/10,000 microm2 in cryptal area; P = .016) than in healthy cats (11.9 +/- 3.0 cells/10,000 microm2) and MHC class II expression by enterocytes also was more pronounced in these cats showing an overall intensity of expression of 7.1 +/- 4.0 cells/10,000 microm2 in cats with IBD as opposed to 0.0 +/- 0.0 cells/10,000 microm2 to 0.3 +/- 0.7 cells/10,000 microm2 in healthy cats. These findings suggest that a subtle immunologic dysregulation occurs in spontaneously arising feline IBD.     

Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats

OBJECTIVE: To evaluate the accuracy of endoscopic biopsy (EB) specimens for diagnosis of alimentary tract lymphosarcoma in cats. DESIGN: Prospective study. ANIMALS: 22 cats with inflammatory bowel disease (IBD) or alimentary tract lymphosarcoma. PROCEDURES: Endoscopic biopsy specimens were obtained during endoscopy of the stomach and duodenum immediately prior to laparotomy or laparoscopic surgery, during which full-thickness biopsy (FTB) specimens were obtained. Accuracy of histopathologic diagnoses was compared between EB and FTB specimens. RESULTS: Lymphosarcoma was diagnosed in 10 cats on the basis of FTB specimens. Lymphosarcoma was detected in the jejunum and ileum in all 10 cats, in the duodenum in 9 cats, and in the stomach in 4 cats. In the same 10 cats, EB findings indicated a diagnosis of lymphosarcoma in 3 cats and were suggestive but inconclusive for lymphosarcoma in 3 cats. Lymphosarcoma was correctly diagnosed via gastric EB specimens in 3 of the 4 cats with gastric lymphosarcoma but evaluation of EB specimens led to an incorrect diagnosis of IBD in 4 cats with small intestinal lymphosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE: EB specimens were useful for diagnosis of gastric lymphosarcoma but were not adequate for differentiating between IBD and lymphosarcoma in the small intestine. Because the most common sites of alimentary tract lymphosarcoma in cats are the jejunum and ileum, FTB specimens of those sites should be obtained via laparotomy or laparoscopy for accurate diagnosis. Laparoscopy may be a minimally invasive alternative to endoscopy and laparotomy for obtaining diagnostic biopsy specimens.     

ULTRASONOGRAPHIC FINDINGS IN DOGS AND CATS WITH GASTROINTESTINAL PERFORATION

A retrospective study was performed to evaluate the sonographic features of gastrointestinal (GI) perforation in dogs and cats. Sonographic findings in 19 animals (14 dogs and 5 cats) included regional bright mesenteric fat (19), peritoneal effusion (16), fluid-filled stomach or intestines (12), GI wall thickening (11), presence of free air (9), loss of GI wall layering (9), regional lymphadenopathy (8), reduced GI motility (7), pancreatic changes (4), corrugated intestines (4), presence of a mass (3), presence of a foreign body (3), and mineralization of the gastric wall (1). In 14 patients, "perforation" was listed as a differential diagnosis by the sonographer. Abdominal radiographs and radiographic reports were available for 14 patients. Radiographic findings were decreased serosal detail (12), free air (8), peritoneal contrast medium (1), and suspected foreign body (1). GI perforation was listed as radiographic diagnosis in eight patients, seven of which had evidence of pneumoperitoneum, and one had leakage of contrast material on an upper GI study. In 9/14 patients with radiography, "GI perforation" was listed as a sonographic diagnosis. In three patients in which free air was diagnosed sonographically, radiographs were either not available (2) or the presence of free air was not detected at presentation (1). Peritoneal fluid analysis was performed in nine patients, five of which were identified as septic inflammation, and the remaining four were classified as neutrophilic inflammation with no etiologic agent identified. The histologic or surgical diagnoses were as follows: three intestinal surgical dehiscence; one percutaneous endoscopic gastrostomy tube site leakage; one duodenal adenocarcinoma; one ileocolic lymphoma; one trichobezoar; one ascarid impaction; and one bobby pin foreign body. In the remaining 10 patients, a focal area of gastric/intestinal ulceration or transmural necrosis with perforation was identified without evidence of an underlying cause.     

The relationship of mucosal bacteria to duodenal histopathology, cytokine mRNA, and clinical disease activity in cats with inflammatory bowel disease

Feline inflammatory bowel disease (IBD) is the term applied to a group of poorly understood enteropathies that are considered a consequence of uncontrolled intestinal inflammation in response to a combination of elusive environmental, enteric microbial, and immunoregulatory factors in genetically susceptible cats. The present study sought to examine the relationship of mucosal bacteria to intestinal inflammation and clinical disease activity in cats with inflammatory bowel disease. Duodenal biopsies were collected from 27 cats: 17 undergoing diagnostic investigation of signs of gastrointestinal disease, and 10 healthy controls. Subjective duodenal histopathology ranged from normal (10), through mild (6), moderate (8), and severe (3) IBD. The number and spatial distribution of mucosal bacteria was determined by fluorescence in situ hybridization with probes to 16S rDNA. Mucosal inflammation was evaluated by objective histopathology and cytokine profiles of duodenal biopsies. The number of mucosa-associated Enterobacteriaceae was higher in cats with signs of gastrointestinal disease than healthy cats (P<0.001). Total numbers of mucosal bacteria were strongly associated with changes in mucosal architecture (P<0.001) and the density of cellular infiltrates, particularly macrophages (P<0.002) and CD3(+)lymphocytes (P<0.05). The number of Enterobacteriaceae, E. coli, and Clostridium spp. correlated with abnormalities in mucosal architecture (principally atrophy and fusion), upregulation of cytokine mRNA (particularly IL-1, -8 and -12), and the number of clinical signs exhibited by the affected cats. These data establish that the density and composition of the mucosal flora is related to the presence and severity of intestinal inflammation in cats and suggest that mucosal bacteria are involved in the etiopathogenesis of feline IBD.