Background: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described. Objective: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies. Methods: We reviewed medical records of pet dogs with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median progression-free, and overall survival times and cause of death were recorded for multivariate analysis. Results: Ninety five dogs (56 male; mean age = 8.3 years) were included, but nine were excluded as final pathology was non-neoplastic. Gross total resection was reported in 81 cases based on postoperative MRI. Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with seizures, being the most common presenting clinical sign. Median survival after surgery was 723 days (95% CI 343–1103) for grade II tumors, 301 days (197–404) for grade III and 200 days (126–274) for grade IV (p = .009 Kaplan–Meier survival analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan–Meier test, p = .22) did not predict survival. Conclusions: This study establishes normative data for a model exploiting dogs with naturally occurring glioma, which can be used to test novel therapies prior to translation to human trials. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy, and immunotherapy.
1 January 2017 in Journal of Veterinary Internal Medicine
A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder.
1 January 2018 in Journal of the American Veterinary Medical Association
OBJECTIVE To assess the relationship between preoperative volume of primary intracranial gliomas in dogs as determined via MRI and survival time after surgical debulking and adjunctive immunotherapy. DESIGN Retrospective cohort study. ANIMALS 47 client-owned dogs enrolled in clinical trials regarding glioma treatments. PROCEDURES Medical records of all dogs undergoing craniotomy at the University of Minnesota Veterinary Medicine Center with histologically confirmed glioma between 2008 and 2015 were retrospectively reviewed, and outcome data were collected. Preoperative T2-weighted or post–gadolinium administration T1-weighted MRI scans, performed at several referral institutions with scanners of magnet strengths ranging from 0.5 to 3.0 T, were used to measure tumor volumes as a percentage of total calvarial volume. Data were analyzed to assess the effect of each 2% fraction of tumor volume on median survival time (MST) after surgery and adjuvant treatment. RESULTS Tumor volumes ranged from 0.5% to 12.2% of total intracranial volume. Overall MST was 185 days (range, 2 to 802 days). No association was identified between preoperative tumor volume and MST. Only 3 (6%) dogs had low-grade tumors that had relatively small volumes, measuring 1.4%, 2.1%, and 4.3% of total calvarial volume. The MST for these 3 dogs (727 days) was longer than that for high-grade tumors (174 days); however, owing to the low number of dogs with low-grade tumors, no statistical comparison was performed. CONCLUSIONS AND CLINICAL RELEVANCE Preoperative tumor volume determined via MRI was neither associated with nor predictive of outcome following surgery and adjunctive treatment for dogs with glioma. Tumor grade was predictive of outcome, but unlike tumor volume that was measured with MRI, invasive biopsy was necessary to definitively diagnose tumor grade.
15 December 2018 in Journal of the American Veterinary Medical Association
OBJECTIVE To determine incidence of and risk factors for major complications occurring in dogs within 30 days after cytoreductive surgery performed by a single pair of surgeons for treatment of suspected primary intracranial masses. DESIGN Retrospective cohort study. ANIMALS 160 client-owned dogs that underwent cytoreductive surgery for treatment of suspected primary intracranial masses between January 2009 and December 2015 at a veterinary teaching hospital. PROCEDURES Medical records were retrospectively reviewed for complications occurring within 30 days after surgery. Data (eg, signalment, clinical signs, previous treatments, preoperative neurologic examination findings, neuroanatomical location, time from onset of clinical signs to surgery, surgical approach, and histopathologic diagnosis) were analyzed for associations with death and with development of major complications other than death. RESULTS 21 (13.1%) dogs died (11 during hospitalization and 10 after discharge) and 30 (18.8%) developed major complications other than death during the first 30 days after surgery. Dogs with abnormal preoperative neurologic examination findings were more likely to develop complications or die. Dogs undergoing a suboccipital approach were more likely to die. The most common postoperative complications other than death were seizures (n = 18 [11.3%]), worsening of neurologic status (6 [3.8%]), and aspiration pneumonia (6 [3.8%]). CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study provided valuable information on predisposing factors, odds of major complications or death, and incidences of major complications or death in dogs during the first 30 days after undergoing cytoreductive surgery for treatment of suspected primary intracranial masses. Careful case selection may help improve outcomes and minimize complications.
1 January 2019 in Journal of the American Animal Hospital Association
A 16 wk old intact female Gordon setter was examined for a 2 wk history of progressive cerebellovestibular ataxia. Eosinophilia was found on complete blood count, and the remaining blood work was normal. A trial treatment with clindamycin and anti-inflammatory prednisone did not result in improvement of clinical signs; therefore, the dog was euthanized. On histopathologic examination, cross sections of a 75 μm wide nematode larva with a 5 μm cuticle, prominent lateral cords, lateral alae, and coeloemyelian musculature were identified in a focally extensive region of cerebellar necrosis. The size and morphology of the parasites was most consistent with Baylisascaris procyonis . This case highlights a rare but important zoonotic disease that should be considered as a differential diagnosis in any dog exhibiting acute, progressive central nervous system signs, and peripheral eosinophilia. The index of suspicion should be elevated in dogs with an unknown deworming history and known or suspected exposure to raccoons. Because most anthelminthics have been shown to be effective against B. procyonis , annual deworming is recommended in the at-risk population to reduce the likelihood of aberrant migration and zoonosis.
Introduction: French bulldogs are one of the most popular dog breeds in the United States and are also among breeds with the highest risk for developing high-grade glioma (HGG). With limited treatment options and high translational value for studying canine HGG to advance understanding of human glioblastoma (GB), a variety of novel treatment options have been investigated. In other forms of cancer, immunotherapy has shown promising results, garnering interest in the treatment of HGG. Yet, when an immunotherapy-based clinical trial was conducted, a marked survival disparity in French bulldog patients compared to other breeds was observed.Methods: This retrospective, multi-institutional study was conducted to examine survival outcomes in immunotherapy-treated French bulldogs compared to closely related breeds, and to French bulldogs treated with several other treatment modalities.Results: French bulldogs treated with immunotherapy experienced significantly shorter overall survival (OS) than boxers and Boston terriers (132 vs. 221 days, respectively). French bulldogs treated with immunotherapy had no significant difference in OS compared to French bulldogs treated palliatively, whereas dogs treated with either a novel therapy involving sonodynamic therapy or stereotactic radiation therapy had significantly longer OS.Discussion: This study provides evidence for an immunotherapy-resistant form of HGG in French bulldogs, suggesting that the breed harbors key molecular differences affecting the tumor and tumor-immune microenvironment and subsequent poor response to treatment.