The echocardiographic pulmonary to left atrial ratio: A noninvasive variable for the hemodynamic classification of pulmonary hypertension in dogs.

BACKGROUND: Hemodynamic classification of pulmonary hypertension (PH) has important clinical implications. However, only a few echocardiographic variables have been used to hemodynamically classify PH in dogs. OBJECTIVE: To evaluate the echocardiographic pulmonary to left atrial ratio index (ePLAR) in dogs with PH. ANIMALS: Forty-six dogs with intermediate to high probability of PH. METHODS: Cross-sectional study. Variables were compared between dogs with precapillary PH [PrePH (n = 24)] vs postcapillary PH [PostPH (n = 22)], and with combined PH [CombPH (n = 14)] vs isolated PH [IsoPH (n = 8)] using the t-, Mann-Whitney, Pearson's Chi, or Fisher's exact test. The receiver operating characteristic curve and Youden index were used to identify the optimal ePLAR cutoff value to differentiate among the groups, intraclass correlation coefficients (ICC) were used to determine the reliability of measurements. RESULTS: The mean (SD) ePLAR of the PrePH was higher than that of the PostPH group [0.36 (0.13) vs 0.26 (0.09), respectively; P = .005]. The median (interquartile range) ePLAR of the CombPH was higher than that of the IsoPH subgroup [0.29 (0.24-0.38), vs 0.20 (0.16-0.23), respectively; P = .001]. The best cutoff value of ePLAR for identifying IsoPH was <0.245 [AUC at cutoff point = 0.86; sensitivity (95% confidence interval [CI]) = 0.71 (0.47-0.95); specificity (95% CI) = 1 (0.76-1)]. The ICC analysis indicated a high degree of reliability. CONCLUSIONS AND CLINICAL IMPORTANCE: ePLAR can be considered a valid noninvasive variable to hemodynamically classify PH in dogs with an intermediate to high probability of PH. Assessment of ePLAR can be useful in the therapeutic management of PH in dogs.

Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.

Understanding relationships between spontaneous cancer in companion (pet) canines and humans can facilitate biomarker and drug development in both species. Towards this end we developed an experimental-bioinformatic protocol that analyzes canine transcriptomics data in the context of existing human data to evaluate comparative relevance of canine to human cancer. We used this protocol to characterize five canine cancers: melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, in 60 dogs. We applied an unsupervised, iterative clustering method that yielded five co-expression modules and found that each cancer exhibited a unique module expression profile. We constructed cancer models based on the co-expression modules and used the models to successfully classify the canine data. These canine-derived models also successfully classified human tumors representing the same cancers, indicating shared cancer biology between canines and humans. Annotation of the module genes identified cancer specific pathways relevant to cells-of-origin and tumor biology. For example, annotations associated with melanin production (PMEL, GPNMB, and BACE2), synthesis of bone material (COL5A2, COL6A3, and COL12A1), synthesis of pulmonary surfactant (CTSH, LPCAT1, and NAPSA), ribosomal proteins (RPL8, RPS7, and RPLP0), and epigenetic regulation (EDEM1, PTK2B, and JAK1) were unique to melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, respectively. In total, 152 biomarker candidates were selected from highly expressing modules for each cancer type. Many of these biomarker candidates are under-explored as drug discovery targets and warrant further study. The demonstrated transferability of classification models from canines to humans enforces the idea that tumor biology, biomarker targets, and associated therapeutics, discovered in canines, may translate to human medicine.

Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma.

BACKGROUND: The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30-40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters. RESULTS: Investigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09). CONCLUSIONS: The highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.

Factors associated with survival in dogs with a histopathological diagnosis of hepatocellular carcinoma: 94 cases (2007-2018).

Background: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in dogs. Despite this, relatively few reports of this disease exist pertaining to prognostic factors and outcome. Aim: To evaluate factors associated with survival in dogs with all subtypes of HCC diagnosed on histopathology. Methods: A retrospective single institutional study was carried out on 94 client-owned dogs with a histopathologic diagnosis of HCC between 2007 and 2018 obtained by biopsy (21/94) or attempted definitive resection (73/94). Signalment, preoperative features, surgical findings, and postoperative outcomes were recorded. Associations between survival to discharge data were collected and univariable logistical regression was carried out. Kaplan-Meier survival analysis was carried out to identify negative risk factors for long-term prognosis. Results: The median survival time (MST) for all patients was 707 days (95% CI = 551-842). MST was not significantly different (p > 0.05) between patients who had suspected versus incidentally diagnosed HCC (695 vs. 775 days), between complete versus incomplete surgical margins (668 vs. 834 days), or between patients with massive subtype versus nodular/diffuse subtype (707 vs. 747 days). Logistical regression identified an association with the excision of the right medial lobe and risk of perioperative death (OR = 9.2, CI 1.5-55.9, p = 0.016). An American Society of Anesthesiologists score ≥4, disease present within the quadrate lobe, and elevated blood urea nitrogen, potassium or gamma-glutamyltransferase were identified as negative prognosticators during multivariable Cox regression. Preoperative imaging (ultrasound or CT) agreed with the surgical location in 91% of the cases. Preoperative cytology was consistent with a diagnosis of HCC in 15/32 (46.9%) cases. Conclusion: Type of diagnosis (incidental vs presumed), completeness of excision, and subtype were not associated with MST in this study. Preoperative identification of tumors within the central division may be related to a less favorable outcome. Results of preoperative cytology were not highly sensitive for identifying a malignancy.

Variation of apoptotic and proliferative activity among lymphoma subtypes in dogs: A flow cytometric study.

Tumor growth depends on both proliferative and apoptotic rate of neoplastic cells. High proliferation index is a well-known negative prognostic factor in canine lymphomas, whereas little is known about apoptotic activity. We describe proliferative and apoptotic rates in different canine lymphoma subtypes at diagnosis. Flow cytometry (FC) was used to assess the percentage of proliferating cells (Ki67%) and of apoptotic cells (AnnV%) in 128 lymph node (LN) aspirates from dogs with lymphoma. Proliferation/apoptosis ratio (PAR) and turnover index (TI; Ki67% + AnnV%) were then calculated for each case. High-grade B-cell lymphomas showed high values for both Ki67% and AnnV%, low-grade B-cell lymphomas showed low Ki67% and high AnnV%, high-grade T-cell lymphomas showed high Ki67% and low AnnV%, and low-grade T-cell lymphomas showed low levels of both parameters. Lymphoblastic lymphomas had the highest PAR values. High-grade B-cell lymphomas had the highest TI values while small clear cells lymphomas the lowest. The panorama of proliferative and apoptotic activity widely varies among lymphoma subtypes. Our results lay the ground for future clinical and pharmacological studies.

The role of COX expression in the prognostication of overall survival of canine and feline cancer: A systematic review.

Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several malignancies associated with histologic criteria of malignancy and worse prognosis, COX-1 has also been linked to some forms of cancer. With the present review our aim was to summarize the current state of knowledge and clarify if and in which type of tumours COX-1 and/or COX-2 expression have real prognostic implications. We searched PubMed database for prognostic studies using predefined inclusion criteria in order to ascertain the prognostic value of COX-1 and COX-2 in malignant neoplasia in dogs and cats. Eighteen studies were analysed. COX-2 was shown to be a negative prognostic factor in canine and feline mammary tumours, canine mast cell tumour, canine melanoma, canine osteosarcoma and canine renal cell carcinoma. COX-1 showed a negative prognostic value in feline oral squamous cell carcinoma (SCC). We found high heterogeneity among studies regarding COX immunohistochemical evaluation methodology even in the same type of neoplasia pointing out the need for its standardization at least by tumour type. The available data support the use of COX-2 as a prognostic factor in canine (mammary carcinoma, mast cell tumour, melanoma, osteosarcoma and renal carcinoma) and feline (mammary carcinoma) cancers. For COX-1, its use is advised in feline oral SCC.

Pituitary tumour types in dogs and cats.

Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tumours are usually classified as adenomas and should only be classified as carcinomas when there is evidence of metastatic spread of the tumour, which is rare. Despite the benign nature of most pituitary tumours, they can still compress or invade neighbouring tissues. Pituitary tumours can be functional (hormonally active) or non-functional (hormonally silent). The aim of this review was to provide an overview of the different pituitary tumour types in dogs and cats that have been reported in the literature. In dogs, the most common pituitary tumour type is the corticotroph adenoma, which can cause pituitary-dependent hypercortisolism. In cats, the most common pituitary tumour is the somatotroph adenoma, which can cause hypersomatotropism, and the second-most common is the corticotroph adenoma. A lactotroph adenoma has been described in one dog, while gonadotroph, thyrotroph and null cell adenomas have not been described in dogs or cats. Hormonally silent adenomas are likely underdiagnosed because they do not result in an endocrine syndrome. Tools used to classify pituitary tumours in humans, particularly immunohistochemistry for lineage-specific transcription factors, are likely to be useful to classify canine and feline pituitary tumours of unknown origin. Future studies are required to better understand the full range of pituitary adenoma pathology in dogs and cats and to determine whether certain adenoma subtypes behave more aggressively than others. Currently, the mechanisms that underlie pituitary tumorigenesis in dogs and cats are still largely unknown. A better understanding of the molecular background of these tumours could help to identify improved pituitary-targeted therapeutics.

Genetics of canine diabetes mellitus part 2: Current understanding and future directions.

Part 1 of this 2-part review outlined the importance of disease classification in diabetes genetic studies, as well as the ways in which genetic variants may contribute to risk of a complex disease within an individual, or within a particular group of individuals. Part 2, presented here, describes in more detail our current understanding of the genetics of canine diabetes mellitus compared to our knowledge of the human disease. Ongoing work to improve our knowledge, using new technologies, is also introduced.

[Diagnostics in epilepsy - potential of magnetic resonance imaging]. / Diagnostik der Epilepsie ­ Möglichkeiten der Magnetresonanztomografie.

Epilepsy is a common neurologic disease frequently encountered by small animal practitioners. The disease comprises a multiplicity of clinical presentations and etiologies and often necessitates a comprehensive as well as cost-intensive diagnostic workup. This is mandatory in order to be able to diagnose or exclude a metabolic cause of the seizures and to distinguish between idiopathic and structural epilepsy. The examination by means of magnetic resonance imaging (MRI) represents a central component of the diagnostic workup, which in turn has essential effects on treatment and prognosis. In order to achieve standardized examination and comparable results, it is of utmost importance to use defined MRI protocols. Accordingly, communication and interaction between clinical institutions may be facilitated and as of yet undetected structural changes might be recorded in future MRI techniques. This review article sets particularly emphasis on the definition and classification of epilepsy as well as its diagnostic imaging procedures and refers to statistics and specialists' recommendations for the diagnostic workup in dogs.

Variability in tumor margin reporting for soft tissue sarcoma and cutaneous mast cell tumors in dogs: A systematic review.

OBJECTIVE: To identify which classification systems have been used for tumor margin reporting and to determine whether factors (publication year, tumor type, and specialty of the contributing authors) influenced trends in margin reporting within literature describing canine soft tissue sarcoma (STS) and cutaneous mast cell tumors (MCT). STUDY DESIGN: Systematic literature review. METHODS: Eligible articles were identified through electronic database searches performed for STS and MCT. Data abstracted from relevant studies included publication year, author list, specialty of contributing authors, criteria used to report the planned surgical margins, and the status of histologic margins. Categorization of papers was based on the classification systems used to report surgical and histologic tumor margins. RESULTS: Fifty-three articles were included, 11 on STS, 37 on MCT, and five that included both tumor types. Criteria for classifying the planned surgical margins were described in only 50.9% of studies. Articles that listed a veterinary surgeon as a contributing author (P = .01) and STS articles compared to MCT papers (P = .01) were more likely to report surgical margins. Most (56.6%) studies reported the status of histologic margins dichotomously as "complete" or "incomplete." Although a previously published consensus statement recommended that quantitative criteria be used to report histologic margins, only 7.5% of articles used quantitative methods. CONCLUSION: Classification systems used for reporting tumor margins were highly variable among studies. CLINICAL SIGNIFICANCE: The findings of this review provide evidence that a standardized classification system for reporting surgical and histologic tumor margins is required in veterinary medicine. A universal system may support more consistent reporting of neoplastic biopsy specimens and allow for more meaningful comparisons across research studies.

Canine atrial fibrillation: Pathophysiology, epidemiology and classification.

Atrial fibrillation (AF) is the most common non-physiological arrhythmia in dogs and humans. Its high prevalence in both species and the impact it has on survival time and quality of life of affected patients, makes it a very relevant topic of medical research. Significant developments in understanding the mechanisms underlying this arrhythmia in humans has occurred over the last decades and some of this knowledge is being applied to veterinary medicine, despite the many differences between species. This article reviews the current understanding of the pathophysiology of AF. The epidemiology and classification of AF in dogs will also be discussed.

p53 Expression in Canine Liposarcoma Correlates With Myxoid Variant and Higher Proliferative Activity.

Canine liposarcoma is classified as well differentiated (WDL), dedifferentiated (DDL), myxoid (ML), and pleomorphic (PL). Overexpression of the protooncogene MDM2 has been reported in WDL and DDL, but little is known regarding the role of p53 in their tumorigenesis. The aim of this study was to assess p53 expression in canine liposarcoma and compare it with subtype, grade, mitotic count (MC), Ki67 labeling index (LI), and MDM2 expression. Forty-seven cases were included (13 WDL, 3 DDL, 7 ML, and 24 PL); 17 were MDM2-positive (13 WDL, 3DDL, and 1ML). Five were p53-positive (4 ML and 1 WDL) but DDL and PL were consistently negative. p53 expression correlated with higher Ki67-LI, higher MC, and myxoid histotype. No correlation was found with grade and MDM2 expression. Based on these results canine liposarcoma seems to embody a group of neoplasms whose subtypes, especially ML, may represent distinct diseases rather than morphological variants of the same entity.

A retrospective study of salivary gland diseases in 179 dogs (2010-2018).

Salivary gland diseases are well characterized in human medicine but are uncommonly reported in dogs. Herein we describe the clinical and pathologic features of 179 canine salivary gland biopsy submissions to the Athens Veterinary Diagnostic Laboratory from 2010 to 2018. The mean age of affected dogs was 8.5 y; no sex or breed predisposition was evident. The main reason for sample submission was regional swelling (107 cases; 59.7%). Extraoral (major) salivary glands were affected in 125 cases (69.8%), and oral (minor) salivary glands were affected in 43 cases (24% of cases). The location of the lesion (extraoral or oral) was not specified in 11 cases (6.1%). The diagnoses included nonspecific sialoadenitis (89 cases; 49.7%), normal salivary gland (42 cases; 23.4%), neoplasia (36 cases; 20.1%), salivary gland lipomatosis (7 cases; 3.9%), necrotizing sialometaplasia (4 cases; 2.2%), and traumatic hemorrhage (1 case; 0.5%). Most cases of sialoadenitis (63 cases), neoplasia (23 cases), and lipomatosis (5 cases), as well as all cases of necrotizing sialometaplasia and the only case of traumatic hemorrhage, affected extraoral glands. Most neoplasms (32 cases, 88.8% of the tumors) were epithelial and malignant, followed by round cell tumors (2 cases; 5.5%), a carcinosarcoma (1 case; 2.7%), and a tumor of undetermined histogenesis (1 case; 2.7%).

Retrospective survey of endoparasitism identified in feces of client-owned dogs in North America from 2007 through 2018.

Our main study objective was to determine the prevalence and trend of parasitic infection in client-owned dogs examined at the veterinary parasitology diagnostic laboratory of Oklahoma State University over the past 12 years. All results of centrifugal flotation, saline direct smear, sedimentation, Baermann, acid-fast staining for Cryptosporidium detection, and Giardia antigen examinations on fecal samples from client-owned dogs submitted to the Boren Veterinary Medical Hospital and Oklahoma Animal Disease Diagnostic Laboratory of Oklahoma State University from 2007 through 2018 were included. The impact of sex, age, and seasonality on the prevalence of parasitic infection was also statistically evaluated. A total of 7,409 cases were included for this study. Majority of cases (79.58%; 5,896/7,409) did not include any parasites, eggs, larva, oocysts, or cysts. Approximately 15.41% (1,142/7,409) of client-owned dogs were infected by at least one parasite, and 5.01% (371/7,409) of dogs were infected by multiple parasites. The most common parasite stage observed was Ancylostoma eggs (8.23%; 610/7,409), followed by Cystoisospora oocysts (5.02%; 372/7,409), Giardia cysts/antigen (4.06%; 301/7,409), Trichuris vulpis eggs (2.74%; 203/7,409), Toxocara canis eggs (2.54%; 188/7,409), Dipylidium caninum proglottids/egg packets (0.84%; 62/7,409), taeniid proglottids/eggs (0.47%; 35/7,409), Sarcocystis sporocysts (0.38%; 28/7,409), Cryptosporidium oocysts (0.30%; 22/7,409), Strongyloides stercoralis larvae (0.20%; 15/7,409), Alaria eggs (0.19%; 14/7,409), Toxascaris leonina eggs (0.18%; 13/7,409), Capillaria eggs (0.16%; 12/7,409), Hammondia-like small coccidian oocysts (0.16%; 12/7,409), Uncinaria stenocephala eggs (0.13%; 10/7,409), Spirometra eggs (0.09%; 7/7,409), Physaloptera eggs (0.09%; 7/7,409), Heterobilharzia americana eggs (0.08%; 6/7,409), Nanophyetus salmincola eggs (0.08%; 6/7,409), trichomonads (0.08%; 6/7,409), Mesocestoides proglottids/eggs (0.05%; 4/7,409), Baylisascaris eggs (0.01%; 1/7,409), Macracanthorhynchus eggs (0.01%; 1/7,409), and Paragonimus kellicotti eggs (0.01%; 1/7,409). In addition to endoparasites, some ectoparasites, such as Demodex mites (0.22%; 16/7,409), Otodectes cynotis mites (0.01%; 1/7,409), Rhipicephalus sanguineus ticks (0.01%; 1/7,409), and Sarcoptes scabiei mites (0.01%; 1/7,409), were detected by fecal examinations. Pseudo/spurious parasites were identified in approximately 4.35% of cases (322/7,409). There was no statistically significant difference for parasite prevalence between sexes (p = 0.3231). However, statistically significant differences were observed with certain parasites when compared by age groups, and generally, prevalence of parasitism decreased as age of client-owned dogs increased (p < 0.0001). Statistical analyses also revealed significant differences by months (p = 0.0013). Overall, the prevalence of parasitic infection in client-owned dogs decreased over the past 12 years (p < 0.0001).

Retrospective evaluation of a modified human lung cancer stage classification in dogs with surgically excised primary pulmonary carcinomas.

The stage classification for canine primary pulmonary carcinomas (PPC) was last updated in 1980. In people, the human lung cancer stage classification (HLCSC) (currently in its eighth edition) plays an integral role in diagnostic and therapeutic decision-making and is prognostic despite a heterogeneous population of tumours. The objective of this retrospective case study was to evaluate the prognostic significance of a canine lung carcinoma stage classification (CLCSC) adapted from the HLCSC by removal of substage for ease of application to canine PPC. A secondary objective was to evaluate the effect of adjuvant chemotherapy. Medical records of 71 dogs with histologically confirmed PPC were reviewed. All dogs underwent surgical excision of the primary lung tumour. Primary tumour features (referring to T1-T4 stages) and TNM stages (1-4) were assigned using the CLCSC. Canine lung carcinoma stage was I (n = 7), II (n = 32), III (n = 24) and IV (n = 8). Median survival time was 952, 658, 158 and 52 days for stages I-IV, respectively. Primary tumour features (T1-T4), incomplete surgical excision, presence of lymph node metastasis and tumour grade were independent prognostic indicators for overall survival. Twenty-six dogs received adjuvant chemotherapy; however, no statistically significant benefit was found. The CLCSC primary tumour features and stage classification were highly prognostic for survival in dogs with PPC. We propose further application and evaluation of this update to canine PPC stage classification. Given the poor prognosis of advanced stage canine PPC, novel treatments are needed.

Simultaneous differential detection of canine blood parasites: Multiplex high-resolution melting analysis (mHRM).

Recently, the incidence of canine infection by the tick-borne parasites Babesia spp., Hepatozoon canis, Ehrlichia canis and Anaplasma platys has been increasing globally. We have developed a multiplex high-resolution melting analysis (mHRM) technique to reduce the time demands and costs associated with detecting haemoparasites in canine blood, while increasing the degree of reliability of this method of analysis. We have designed primers that are specific for protozoans (B. vogeli and H. canis) and Rickettsia-like bacteria (E. canis and A. platys) based on the 18S or 16S rDNA sequences, respectively. Two primer pairs (Protz18S-C and Bact16S-A) were found to be suitable for detecting these agents since their melting temperatures (Tm) exhibited discernible differences among the four haemoparasites, A. platys, B. vogeli, E. canis and H. canis (83.10 °C, 82.41 °C, 80.37 °C and 78.56 °C, respectively). The sequences acquired from these PCR products were >94 % identical to those of A. platys, B. vogeli, E. canis and H. canis in GenBank. The limit of detection (LOD) for B. vogeli, E. canis and A. platys was 103 copies/µl, while the LOD for H. canis was 104 copies/µl. Of the 68 dogs tested, 28 (41 %) were infected with these agents. The most commonly occurring infection involved E. canis, followed by B. vogeli, A. platys and H. canis, with infection percentages of 26 %, 13 %, 7 % and 6 %, respectively. These results demonstrate that mHRM can serve as a rapid, economical and reliable tool for the detection of parasitic diseases in canine blood for diagnosis and epidemiology.

The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours.

Subcutaneous spindle cell tumours characterized by whorling growth patterns are common in dogs and are identified as a distinct entity. These tumours were misnamed as hemangiopericytomas (HPCs) because of some minor morphological parallels with their human counterparts. In veterinary medicine, the cell of origin of HPC has been under debate for a long time. Some authors have suggested a perivascular origin while others a perineural one. The evidence of the orientation of the neoplastic cells around the vessels and the expression of contractile proteins supported a perivascular origin while S100 expression and an inconsistent vascular connection supported a perineural origin. Despite the morphological similarities with peripheral nerve sheath tumours in humans, the perineural origin was supported mainly by the expression of markers with low specificity. On the contrary, the majority of studies have supported the perivascular origin of 'old' canine HPC. Since a variable degree of myoid-pericytic differentiation was described, the term perivascular wall tumours (PWTs) were suggested to substitute HPC. Once the diagnostic criteria of PWTs were defined, the clinical behaviour and prognostic variables were investigated, demonstrating differences as compared with the group of canine soft tissue sarcomas (STSs) in general. PWTs are less aggressive, mostly locally invasive, and rarely metastasizing. Their behaviour seems to be less influenced by histological grade, suggesting that canine STSs are heterogeneous. The study of the biological behaviour of specific STS tumour types may be valuable in detecting differences which have passed unnoticed when STSs have been studied concomitantly.

Development and validation of a graphic 2D investigator's global assessment instrument for grading the overall severity of atopic dermatitis in dogs.

BACKGROUND: Clinical trials enrolling dogs with atopic dermatitis (AD) use validated instruments that aggregate the extent and severity of selected skin lesions; none of these provides a global assessment of the severity of all lesions. OBJECTIVES: To validate an Investigator Global Assessment (IGA) instrument to globally evaluate the severity of skin lesions in dogs with AD. ANIMALS: Forty dogs with AD. METHODS AND MATERIALS: A 2D graphic IGA (2D-IGA) instrument was created to subjectively score, with a single dot, the overall extent and severity of all canine AD lesions. This tool was tested for its validity (content, construct and criterion), reliability (inter- and intraobserver) and sensitivity to change. RESULTS: The content of the 2D-IGA was first validated by a supportive vote by the International Committee of Allergic Diseases of Animals (ICADA) membership. Its construct was verified by positive correlations between the 2D-IGA scores and those of the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and the Canine Atopic Dermatitis Lesion Index (CADLI) (Spearman's rank-order correlation, P < 0.0001). The positive correlation (P < 0.0001) between an Owner Global Assessment of Disease Severity (OGADS) and the 2D-IGA indirectly satisfied its criterion. Scores graded by the same investigator hours apart and those between investigators were positively correlated (P < 0.0001), thereby validating this scale's intra- and interobserver reliabilities. Finally, the changes in 2D-IGA values during treatment were correlated positively with scores of an Owner Global Assessment of Treatment Efficacy (OGATE; P < 0.0001), thus showing its sensitivity to change. CONCLUSIONS AND CLINICAL IMPORTANCE: This novel 2D-IGA is a simple static graphic instrument that could be useful for clinical trials testing the efficacy of interventions for canine AD.