Colonic gastrointestinal stromal tumor (GIST) presenting with colocolonic intussusception: A rare case report.

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing. Key clinical message: The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.

Tumeur stromale gastro-intestinale du côlon (GIST) présentant une invagination colocolique : un rapport de cas rare. Une femelle bouledogue anglais stérilisée de 8 ans a présenté des vomissements, une hyporexie et une diarrhée d'origine du gros intestin. L'échographie abdominale a révélé une masse colique focale avec une invagination située immédiatement oralement à la masse. L'intussusception englobait le côlon ascendant et transverse et était non réductible. La résection colique et l'anastomose ont été réalisées pour inclure l'intussusception et la masse colique. L'examen histopathologique de la masse a révélé un néoplasme à cellules fusiformes apparaissant dans la paroi musculaire du segment invaginé qui a oblitéré l'architecture normale. L'immunoréactivité cytoplasmique légère à modérée de la population de cellules tumorales pour le CD117 et l'actine des muscles lisses étaient compatibles avec un diagnostic de tumeur stromale gastro-intestinale. Le chien décrit ici est toujours vivant et exempt de maladie évolutive au moment de la rédaction.Message clinique clé :L'ensemble du tractus gastro-intestinal doit être évalué chez tout animal présentant des symptômes gastrointestinaux. Une tumeur stromale gastro-intestinale reste un diagnostic différentiel plausible, quel que soit le segment intestinal atteint, et l'intussusception associée à la tumeur est une constatation clinique rare mais urgente.(Traduit par Dr Serge Messier).

Hepatic Dicrocoelium dendriticum infection in a miniature horse.

A miniature horse which died following humane seizure from an Ontario farm was emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and moderate periportal fibrosis. Eggs and trematodes seen in the liver were identified as Dicrocoelium dendriticum. This appears to be the first reported case of infection of equids in North America with Dicrocoelium dendriticum.

Infection parDicrocoelium dendriticumhépatique chez un cheval miniature. Un cheval miniature qui est mort à la suite d'une saisie humanitaire dans une ferme de l'Ontario était émacié et avait une atrophie séreuse des tissus adipeux. L'autopsie a révélé une atrophie hépatique et une fibrose périportale modérée. Des oeufs et des trématodes observés dans le foie ont été identifiés comme Dicrocoelium dendriticum. Il semblerait qu'il s'agit du premier cas signalé d'infection des équidés par Dicrocoelium dendriticum en Amérique du Nord.(Traduit par Isabelle Vallières).

Bilateral diffuse cystic renal dysplasia in a 9-day-old Thoroughbred filly.

A 9-day-old Thoroughbred filly was presented for diarrhea and lethargy. Diagnostic test results were compatible with severe renal dysfunction. Diffuse cystic lesions of both kidneys were identified on ultrasonographic examination. Postmortem examination confirmed the presence of multiple renal cysts. Congenital nephropathy compatible with bilateral diffuse cystic renal dysplasia was diagnosed.

Dysplasie rénale kystique diffuse bilatérale chez une pouliche Thoroughbred âgée de 9 jours. Une pouliche Thoroughbred âgée de 9 jours a été présentée pour de la diarrhée et de la léthargie. Les résultats des tests diagnostiques étaient compatibles avec une dysfonction rénale grave. Des lésions kystiques diffuses des deux reins ont été identifiées à l'échographie. L'examen postmortem a confirmé la présence de kystes rénaux multiples. Une néphropathie congénitale compatible avec la dysplasie rénale kystique diffuse bilatérale a été diagnostiquée.(Traduit par Isabelle Vallières).

Hepatic alveolar hydatid disease (Echinococcus multilocularis) in a boxer dog from southern Ontario.

A 2-year-old boxer dog from southern Ontario was evaluated because of acute onset lethargy. Exploratory laparotomy revealed a hemorrhagic, destructive, liver mass. Histology, immunohistochemistry, and polymerase chain reaction confirmed Echinococcus multilocularis as the cause of the hepatic mass. This constitutes the first description of endemic E. multilocularis in Ontario.

Hydatidose alvéolaire hépatique(Echinococcus multilocularis)chez un chien Boxer du Sud de l'Ontario. Un chien Boxer âgé de 2 ans du Sud de l'Ontario a été évalué en raison d'un début soudain d'une léthargie. Une laparatomie exploratoire a révélé une masse hépatique hémorragique et destructrice. L'histologie, l'immunohistochimie et l'amplification en chaîne par la polymérase ont confirmé Echinococcus multilocularis comme la cause de la masse hépatique. Il s'agit de la première description d'E. multilocularis endémique en Ontario.(Traduit par Isabelle Vallières).

The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC.

Introduction: Acquired MET gene amplification, MET exon 14 skip mutations, or MET fusions can emerge as resistance mechanisms to tyrosine kinase inhibitors (TKIs) in patients with lung cancer. The efficacy and safety of combining MET TKIs (such as crizotinib, capmatinib, or tepotinib) with parent TKIs to target acquired MET resistance are not well characterized. Methods: Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added. Clinicopathologic features, radiographic response (by means of Response Evaluation Criteria in Solid Tumors version 1.1), survival outcomes, adverse events (AEs) (by means of Common Terminology Criteria for Adverse Events version 5.0), and genomic data were collected. Survival outcomes were assessed using Kaplan-Meier methods. Multivariate modeling adjusted for lines of therapy, brain metastases, TP53 mutations, and oligometastatic disease. Results: Within the MET cohort, median age was 56 years (range: 36-83 y). Most patients were never smokers (28 of 41, 68.3%). Baseline brain metastases were common (21 of 41, 51%). The most common oncogenes in the MET cohort were EGFR (30 of 41, 73.2%), ALK (seven of 41, 17.1%), and ROS1 (two of 41, 4.9%). Co-occurring TP53 mutations (32 of 41, 78%) were frequent. Acquired MET alterations included MET gene amplification (37 of 41, 90%), MET exon 14 mutations (two of 41, 5%), and MET gene fusions (two of 41, 5%). After multivariate adjustment, the objective response rate (ORR) was higher in the MET cohort versus the chemotherapy cohort (ORR: 69.2% versus 20%, p < 0.001). Within the MET cohort, MET gene copy number (≥10 versus 6-10) did not affect radiographic response (54.5% versus 68.4%, p = 0.698). There was no difference in ORR on the basis of MET TKI used (F [2, 36] = 0.021, p = 0.978). There was no difference in progression-free survival (5 versus 6 mo; hazard ratio = 0.64; 95% confidence interval: 0.34-1.23, p = 0.18) or overall survival (13 versus 11 mo; hazard ratio = 0.75; 95% confidence interval: 0.42-1.35, p = 0.34) between the MET and chemotherapy cohorts. In the MET cohort, dose reductions for MET TKI-related toxicities were common (17 of 41, 41.4%) but less frequent for parent TKIs (two of 41, 5%). Grade 3 AEs were not significant between crizotinib, capmatinib, and tepotinib (p = 0.3). The discontinuation rate of MET TKIs was 17% with no significant differences between MET TKIs (p = 0.315). Among pre- and post-treatment biopsies (n = 17) in the MET cohort, the most common next-generation sequencing findings were loss of MET gene amplification (15 of 17, 88.2%), MET on-target mutations (seven of 17, 41.2%), new Ras-Raf-MAPK alterations (three of 17, 17.6%), and EGFR gene amplification (two of 17, 11.7%). Conclusions: The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.

Clinical Management of Triple-Class Refractory Multiple Myeloma: A Review of Current Strategies and Emerging Therapies.

Major progress has been made in the upfront treatment of multiple myeloma, but the disease ultimately relapses and leads to death in the vast majority of those afflicted. New treatment strategies and modalities are necessary to treat myeloma in relapse, particularly in cases of triple-refractory status defined by disease progression during or shortly after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibody therapy. In this manuscript, we review recent promising developments in the treatment of triple-class refractory myeloma including bispecific antibodies and T cell engagers, chimeric antigen receptor cellular therapies, as well as chemotherapeutics with novel mechanisms of action.

Unilateral primary carcinoma of the kidney with central nervous system invasion and vertebral lysis in a cat.

Case summary: A young adult female spayed domestic shorthair cat presented for acute hindlimb weakness and anorexia with a 1-month history of lethargy, hyporexia and weight loss. A mass was palpable in the caudolateral abdomen and the left hindlimb was diffusely edematous. Abdominal ultrasound showed hydronephrosis of the left kidney with suspected hydroureter and heterogeneous tissue in the dorsal abdomen. CT evaluation confirmed a mass extending from the left kidney through the lumbar musculature with hydronephrosis, aortic attenuation, caudal vena caval thrombosis and lysis of vertebrae 4 and 5. Fine-needle aspiration of the mass suggested squamous cell carcinoma. Owing to clinical deterioration, euthanasia was elected. At necropsy, the left kidney was firmly adhered to the lumbar region with tissue that obliterated the musculature and surrounded the aorta and vena cava. There was hydronephrosis of the left kidney. Histopathologic evaluation of the mass revealed islands of neoplastic epithelial cells separated by fibrous connective tissue and areas of gradual keratinization with rare squamous metaplasia. The histologic diagnosis was invasive carcinoma with desmoplasia and vascular invasion. Relevance and novel information: Primary carcinomas of the kidney in cats are rare and this report documents a progression of disease not previously reported in cats. This is the second reported case of a primary carcinoma of renal origin with features of squamous cell carcinoma in a cat, and the first with lumbar and vascular invasion. This is also the first use of kidney injury molecule-1 to help investigate tumor differentiation in cats.

Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.

BACKGROUND: Preeclampsia and fetal growth restriction increase cardiopulmonary disease risk for affected offspring and occur more frequently at high-altitude (≥2500 m). Retrospective studies indicate that birth to a preeclampsia woman at high altitude increases the risk of pulmonary hypertension (PH) in later life. This prospective study asked whether preeclampsia with or without fetal growth restriction exaggerated fetal hypoxia and impaired angiogenesis in the fetal lung, leading to neonatal cardiopulmonary circulation abnormalities and neonatal or infantile PH. METHODS AND RESULTS: We studied 79 maternal-infant pairs (39 preeclampsia, 40 controls) in Bolivia (3600-4100 m). Cord blood erythropoietin, hemoglobin, and umbilical artery and venous blood gases were measured as indices of fetal hypoxia. Maternal and cord plasma levels of angiogenic (VEGF [vascular endothelial growth factor]) and antiangiogenic (sFlt1 [soluble fms-like tyrosine kinase]) factors were determined. Postnatal echocardiography (1 week and 6-9 months) assessed pulmonary hemodynamics and PH. Preeclampsia augmented fetal hypoxia and increased the risk of PH in the neonate but not later in infancy. Pulmonary abnormalities were confined to preeclampsia cases with fetal growth restriction. Maternal and fetal plasma sFlt1 levels were higher in preeclampsia than controls and positively associated with PH. CONCLUSIONS: The effect of preeclampsia with fetal growth restriction to increase fetal hypoxia and sFlt1 levels may impede normal development of the pulmonary circulation at high altitude, leading to adverse neonatal pulmonary vascular outcomes. Our observations highlight important temporal windows for the prevention of pulmonary vascular disease among babies born to highland residents or those with exaggerated hypoxia in utero or newborn life.

Predictors of outcome in dogs treated with adjuvant carboplatin for appendicular osteosarcoma: 65 cases (1996-2006).

OBJECTIVE: To determine outcomes and prognostic factors for those outcomes in dogs with appendicular osteosarcoma treated with curative-intent surgery and adjuvant carboplatin. DESIGN: Retrospective case series. ANIMALS: 65 client-owned dogs with appendicular osteosarcoma and no evidence of gross metastatic disease at the time of diagnosis. PROCEDURES: Medical records of dogs that underwent limb amputation or distal ulnectomy and adjuvant carboplatin treatment for appendicular osteosarcoma were reviewed. Adverse effects of chemotherapy and findings regarding preoperative biopsy specimens and postoperative diagnostic imaging were recorded. Signalment, clinical history, and chemotherapy variables were evaluated for associations with outcome. Histologic grade and other variables were evaluated for association with outcome for 38 tumors that were retrospectively graded. RESULTS: The median disease-free interval was 137 days (95% confidence interval [CI], 112 to 177 days). Median survival time was 277 days (95% CI, 203 to 355 days). The 1-, 2-, and 3-year survival rates were 36%, 22%, and 19%, respectively. None of the chemotherapy variables were associated with outcome. Preoperative proteinuria was the only clinical variable associated with poor outcome. Histologic features of tumors associated with a poor outcome were intravascular invasion, mitotic index > 5 in 3 microscopic hpfs, and grade III classification. CONCLUSIONS AND CLINICAL RELEVANCE: Carboplatin administration was well tolerated and resulted in a disease-free interval and median survival time similar to those of other published protocols.

Arthritis and osteomyelitis associated with Enterococcus cecorum infection in broiler and broiler breeder chickens in Ontario, Canada.

In August 2008, an Ontario broiler chicken flock experienced an outbreak of lameness in 4-week-old birds, with morbidity reaching 7% by day 3. Necropsy examination and histopathology revealed arthritis of the hock, stifle, and coxofemoral joints, and femoral and vertebral osteomyelitis. Enterococcus cecorum was isolated from the lesions and identified by 16S ribosomal RNA sequencing. In October 2008, a second case of E. cecorum osteomyelitis involved a flock of 9-week-old broiler breeder chickens, with 2% of the male birds showing reluctance to walk. Necropsy examination revealed osteomyelitis and abscessation of the body of the caudal thoracic vertebra in affected birds, with impingement on the overlying spinal cord.

Ectopic thyroid carcinoma causing right ventricular outflow tract obstruction in a dog.

A 9-year-old Bouvier des Flandres was presented with coughing, lethargy, chylous pleural effusion, and a heart murmur. An echocardiogram revealed the presence of an intracardiac mass causing right ventricular outflow tract obstruction. The mass was successfully removed surgically, using total inflow occlusion. Histopathology and immunohistochemistry identified the tumor as an ectopic thyroid carcinoma. The dog was euthanized 11 months after diagnosis at the request of the owner because of nonresolving chylothorax.

Prostatic abscess in a neutered cat.

A 6-year-old, male castrated domestic shorthair cat was presented for evaluation of lethargy, vomiting, anorexia, and constipation. Physical examination revealed an elevated body temperature and an extramural colonic mass. Abdominal ultrasonography demonstrated a hypoechoic mass measuring 2.2 cm in maximum dimension immediately caudal to the bladder. Cytological evaluation of a fine-needle aspirate confirmed the mass was a prostatic abscess. Abdominal celiotomy and prostatic omentalization were successful in resolving clinical abnormalities. Feline prostatic abscessation is a rare condition that has not been previously reported and may have a good outcome if treated early and appropriately.

A case of primary hypothyroidism causing central nervous system atherosclerosis in a dog.

A 2-year-old, castrated male, Australian shepherd was presented with a history of chronic mild ataxia, obesity, and lethargy. The dog was treated with levothyroxine, but the ataxia worsened. Cranial nerve abnormalities developed and the dog was euthanized. Postmortem examination revealed marked thyroid gland atrophy and widespread, severe central nervous system atherosclerosis.

Natural and experimental infection of neonatal calves with Clostridium difficile.

Clostridium difficile toxins were associated with calf diarrhea in a recent retrospective study; however, no causal relationship has been prospectively investigated. This infection study tested whether the oral inoculation of neonatal calves with a toxigenic strain of C. difficile (PCR-ribotype 077) results in enteric disease. Fourteen 6-24 h old male colostrums-fed Holstein calves, received either three doses of C. difficile (1.4 x 10(8) +/- 3.5 x 10(8) cfu) (n = 8) or sterile culture broth (n = 6). Calves were euthanized on day 6 or after the onset of diarrhea, whichever came first. Fecal and intestinal samples were blindly cultured for C. difficile, and tested for its toxin A/B (C. difficile TOX A/B II ELISA, Techlab). PCR-ribotyping was used to compare inoculated and recovered isolates. Diarrhea was observed in all control calves and 3/8 of inoculated calves (p = 0.03), but it did not occur in calves that tested positive for C. difficile toxins. Fecal toxins were identified only from two controls. PCR-ribotyping confirmed the presence of C. difficile PCR-ribotype 077 in samples of all inoculated calves, but not from controls. The identification of five other PCR-ribotypes in 3/8 (37.5%) and 2/6 (33.3%) of inoculated and control calves, respectively, indicated early natural infection (< or = 24h of age). Five of 14 cecal samples had C. difficile (p = 0.01). In conclusion, the oral administration of C. difficile PCR-ribotype 077 to neonatal calves resulted in fecal/intestinal colonization but not in detection of toxins, or signs of enteric disease. Further studies are required to investigate the clinical relevance of C. difficile in calves.

Inflammatory aural polyp in a horse.

An inflammatory aural polyp was identified in a 1-year-old standardbred filly, which presented with otorrhea and head rubbing. The polyp was removed by traction-avulsion, and the filly showed no subsequent signs of otorrhea. Aural polyps have not been reported in horses, but they are commonly seen in companion animals and humans.

Sinusoidal endothelial cell and hepatic stellate cell phenotype correlates with stage of fibrosis in chronic liver disease in dogs.

We evaluated the extent of hepatic fibrosis in chronic liver disease of dogs using a modification of Ishak's staging criteria for human chronic liver disease, and examined the association of stage of fibrosis with immunophenotypic markers of transdifferentiation of hepatic sinusoidal endothelial cells and hepatic stellate cells. Formalin-fixed, paraffin-embedded, hematoxylin and eosin-stained liver biopsy specimens from 45 case dogs with chronic liver disease and 55 healthy control dogs were scored for the presence and extent of fibrosis. This stage score for fibrosis strongly correlated with upregulated von Willebrand factor (vWF) expression in lobular sinusoidal endothelial cells (Spearman correlation coefficient [SCC] = 0.57, p < 0.05). Immunoreactivity for vWF factor was identified in 68.9% of case biopsies, varying in distribution from periportal to diffuse, whereas vWF immunoreactivity was identified in only 14.5% of control specimens, and was restricted to the immediate periportal sinusoids. The majority of both case and control biopsies exhibited similar prominent lobular perisinusoidal expression of alpha-smooth muscle actin (α-SMA). A minority of specimens (17.8% of case biopsies, 1.8% of control biopsies) exhibited low perisinoidal α-SMA expression, and there was a weak negative correlation between α-SMA expression and stage of fibrosis (SCC = -0.29, p = 0.0037). These results document a method for staging the severity of fibrosis in canine liver biopsies, and show a strong association between fibrosis and increased expression of vWF in hepatic sinusoidal endothelial cells.

A prospective study of sheep and goat abortion using real-time polymerase chain reaction and cut point estimation shows Coxiella burnetii and Chlamydophila abortus infection concurrently with other major pathogens.

From 2009 to 2011, 163 sheep and 96 goat abortion submissions were received at the Animal Health Laboratory, University of Guelph, Ontario, Canada, for gross and histologic examination, as well as real-time polymerase chain reaction (PCR) testing for Chlamydophila abortus and/or Coxiella burnetii. Additional testing included immunohistochemistry for Toxoplasma gondii and Chlamydophila spp., routine bacterial culture and selective culture for Campylobacter spp., examination of modified acid-fast-stained placenta smears, enzyme-linked immunosorbent assay testing for Chlamydophila spp., and virus isolation. The final diagnosis made for each case by individual pathologists, based on gross and histologic lesions, as well as ancillary testing, was used as a standard to determine the significance of C. abortus and C. burnetii infection. Coxiella burnetii was identified by real-time PCR in 113 of 163 (69.0%) and 72 of 96 (75%) sheep and goat abortion submissions, respectively, but was considered to be significant in causing abortion in only 11 of 113 (10%) sheep and 15 out of 72 (21%) goat submissions that tested positive. Chlamydophila abortus was identified by real-time PCR in 42 of 162 (26%) and 54 of 92 (59%) sheep and goat submissions, respectively, but was considered the cause of the abortion in 16 of 42 (38%) sheep and 34 of 54 (63%) goat submissions that tested positive. Optimal sensitivity and specificity cut points for the real-time PCR copy number for C. abortus and C. burnetii were determined using the final pathology diagnosis as the reference test.