Gabriela Seiler

Contrast harmonic ultrasonography of splenic masses and associated liver nodules in dogs

OBJECTIVE To determine whether contrast harmonic ultrasonography (CHUS) can be used in dogs to distinguish splenic hemangiosarcoma from hematoma and to accurately detect and characterize liver nodules. DESIGN Cross-sectional study. ANIMALS 20 dogs with a splenic mass. PROCEDURES Routine abdominal ultrasonography was followed by CHUS of hepatic and splenic lesions. Qualitative evaluation included location, enhancement pattern, and vascularity of lesions. Quantitative evaluation included peak mean pixel intensity, interval to peak intensity, area under the curve (spleen), and liver-to-lesion intensity ratio (liver). Histologic findings were compared with CHUS lesion characteristics. RESULTS Histologic evaluation of the spleen was performed in 19 dogs, resulting in diagnoses of hemangiosarcoma (n=11), hematoma (7), and undifferentiated sarcoma (1). Benign and malignant processes in the spleen were indistinguishable via CHUS. Histologic evaluation of the liver was performed in 18 dogs, resulting in a diagnosis of hemangiosarcoma in 5 dogs. None of the dogs with splenic hematomas had evidence of hepatic lesions by means of conventional or contrast ultrasonography, and none had histologic evidence of liver metastases. In 3 of 18 dogs, isoenhancing liver nodules were detected and all were histologically benign. Five dogs had liver nodules that remained hypoechoic after contrast agent was injected; all had histologic evidence of metastatic hemangiosarcoma. Results of CHUS were used to characterize hepatic metastases with 100% sensitivity and specificity. CONCLUSIONS AND CLINICAL RELEVANCE Contrast harmonic ultrasonography was a noninvasive and accurate means of differentiating metastatic versus benign hepatic disease in dogs with splenic hemangiosarcoma but was not useful in distinguishing splenic hemangiosarcoma from hematoma.

Facet joint geometry and intervertebral disk degeneration in the L5-S1 region of the vertebral column in German Shepherd dogs.

OBJECTIVE To evaluate the possible association between facet joint geometry and intervertebral disk degeneration in German Shepherd Dogs. ANIMALS 25 German Shepherd Dogs and 11 control dogs of similar body weight and condition. PROCEDURE Facet joint angles in the caudal portion of the lumbar region of the vertebral column (L5-S1) were measured by use of computed tomography, and the intervertebral discs were evaluated microscopically. The relationship between facet joint geometry and disk degeneration was evaluated by use of statistical methods. RESULTS German Shepherd Dogs had significantly more facet joint tropism than control dogs, but an association with disk degeneration was not found. However, German Shepherd Dogs had a different facet joint conformation, with more sagittally oriented facet joints at L5-L6 and L6-L7 and a larger angle difference between the lumbar and lumbosacral facet joints, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE A large difference between facet joint angles at L6-L7 and L7-S1 in German Shepherd Dogs may be associated with the frequent occurrence of lumbosacral disk degeneration in this breed.

Safety of contrast-enhanced ultrasonography in dogs and cats: 488 cases (2002-2011)

OBJECTIVE To determine the incidence of adverse events within 24 hours after contrast-enhanced ultrasonography (CEUS) in dogs and cats and compare the risk of death within 24 hours after imaging for animals that underwent ultrasonography with and without injection of a contrast agent. DESIGN Retrospective case-control study. ANIMALS 750 animals (411 case dogs, 238 control dogs, 77 case cats, and 24 control cats). PROCEDURES At 11 institutions, medical records were reviewed of dogs and cats that had CEUS performed (cases) as were medical records of dogs and cats with clinical signs similar to those of case animals that had ultrasonography performed without injection of a contrast agent (controls). Information regarding signalment; preexisting disease; type, dose, and administration route of contrast agent used; immediate (within 1 hour after CEUS) and delayed (> 1 and ≤ 24 hours after CEUS) adverse events; and occurrence and cause of death (when available) was extracted from each medical record. Risk of death within 24 hours after ultrasonography was compared between case and control animals. RESULTS Of the 411 case dogs, 3 had immediate adverse events (vomiting or syncope) and 1 had a delayed adverse event (vomiting). No adverse events were recorded for case cats. Twenty-three of 357 (6.4%) clinically ill case animals and 14 of 262 (5.3%) clinically ill control animals died within 24 hours after ultrasonography; risk of death did not differ between cases and controls. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that CEUS was safe in dogs and cats.

Clinical and Pharmacokinetic Characteristics of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin in Dogs with Splenic Hemangiosarcoma

BACKGROUND Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS Fourteen dogs with splenic HSA. METHODS A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.

Cystosonographic measurements of canine bladder tumours

The purpose of this study was to evaluate the variability of cystosonographic bladder tumor measurements with both operator and bladder volume changes. Ten dogs with bladder tumors were included. In each dog, three operators determined tumor dimensions for three different bladder volumes. Intraclass correlation coefficient was used to assess operator reliability. Response Evaluation Criteria in Solid Tumors (RECIST) and greater than or equal to 50% differences in tumor measurements were used as guidelines. Poor to fair correlations between operators were found for the different tumor dimensions (r(I) = 0.4 - 0.7). The percent differences in tumor dimensions with operator and bladder volume changes were significant enough to misclassify the tumors into the categories of partial response (PR) or progressive disease (PD). These results suggest that cystosonographic measurements of bladder tumors are affected by both changes in operator and bladder volume, and the discrepancies are significant enough to change response classification.

Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in Dogs.

Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and rupture of the gallbladder. The cause of gallbladder mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and protein associates of the culprit mucins with aim to identify causes for abnormal mucus behavior. We established that mucocele formation involves an adoptive excess secretion of gel forming mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging, and mucin-interacting innate defense proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for mucocele formation in dogs.

Histiocytic Sarcoma with Central Nervous System Involvement in Dogs: 19 Cases (2006–2012)

Background Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1–3 animals. Objective The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement. Animals Nineteen dogs with HS examined at veterinary referral hospitals. Methods Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis. Results Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days. Conclusions and Clinical Importance Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.

Transplantation and magnetic resonance imaging of canine neural progenitor cell grafts in the postnatal dog brain.

Cellular transplantation in the form of bone marrow has been one of the primary treatments of many lysosomal storage diseases (LSDs). Although bone marrow transplantation can help central nervous system manifestations in some cases, it has little impact in many LSD patients. Canine models of neurogenetic LSDs provide the opportunity for modeling central nervous system transplantation strategies in brains that more closely approximate the size and architectural complexity of the brains of children. Canine olfactory bulb-derived neural progenitor cells (NPCs) isolated from dog brains were expanded ex vivo and implanted into the caudate nucleus/thalamus or cortex of allogeneic dogs. Canine olfactory bulb-derived NPCs labeled with micron-sized superparamagnetic iron oxide particles were detected by magnetic resonance imaging both in vivo and postmortem. Grafts expressed markers of NPCs (i.e. nestin and glial fibrillary acidic protein), but not the neuronal markers Map2ab or &bgr;-tubulin III. The NPCs were from dogs with the LSD mucopolysaccharidosis VII, which is caused by a deficiency of &bgr;-glucuronidase. When mucopolysaccharidosis VII canine olfactory bulb-NPCs that were genetically corrected with a lentivirus vector ex vivo were transplanted into mucopolysaccharidosis VII recipient brains, they were detected histologically by &bgr;-glucuronidase expression in areas identified by antemortem magnetic resonance imaging tracking. These results demonstrate the potential for ex vivo stem cell-based gene therapy and noninvasive tracking of therapeutic grafts in vivo.

Prevalence of clinical and subclinical middle ear disease in cats undergoing computed tomographic scans of the head.

Three hundred and ten cats that had CT imaging of the head between January 2000 and December 2007 were evaluated retrospectively. Data that were recorded included signalment, presenting complaint, clinical signs, presence of upper respiratory tract disease, and CT findings. One hundred and one cats had evidence of middle ear disease on CT. Thirty-four of the 101 cats (34%) did not have a primary complaint of ear-related disease, clinical signs or physical findings consistent with ear disease, suggesting that the middle ear disease was subclinical. Twenty-seven of the 34 cats (79%) had concurrent nasal disease. Middle ear lesions were chronic in appearance. With the exception of tympanic bulla lysis, CT findings were similar in cats presenting with primary aural disease versus cats with presumptive subclinical middle ear disease. The majority of the cats did not return for treatment of the identified middle ear abnormalities. Subclinical middle ear disease is relatively frequent in cats undergoing CT imaging of the head. Few cats required subsequent treatment for ear disease although follow up was limited. Identification of subclinical middle ear abnormalities on CT should prompt acquisition of a detailed patient history and bilateral otoscopic examination.

MAGNETIC RESONANCE IMAGING FINDINGS ASSOCIATED WITH LATERAL CEREBRAL VENTRICULOMEGALY IN ENGLISH BULLDOGS

Multiple congenital or developmental anomalies associated with the central nervous system have been reported in English Bulldogs. The purpose of this retrospective study was to identify and describe the prevalence and MRI characteristics of these anomalies and their association with presence and degree of cerebral ventriculomegaly. Magnetic resonance imaging studies of 50 English Bulldogs were evaluated. Forty-eight dogs had some degree of cerebral ventriculomegaly, 27 of which had an otherwise normal brain. Presence of lateral ventriculomegaly was not significantly associated with presence of another intracranial lesion. Appearance of the septum pellucidum was variable, ranging from intact to incomplete or completely absent. The corpus callosum was subjectively thinned in all but three dogs, two of which had normal lateral ventricles. Fusion of the rostral colliculi was not found in any dog. A persistent craniopharyngeal canal was identified in one dog. Aqueductal stenosis caused by fusion of the rostral colliculi was not identified in any dog. Findings indicated that cerebral ventriculomegaly is a common finding in English Bulldogs with or without other intracranial lesions, aqueductal stenosis caused by fusion of the rostral colliculi is unlikely to be a common etiology leading to obstructive hydrocephalus, and a large craniopharyngeal canal is a rare finding that has unknown clinical significance at this time.