Arthroscopic Caudal Cruciate Ligament Damage in Canine Stifles with Cranial Cruciate Ligament Disease.

OBJECTIVE: The aim of this study was to describe the arthroscopic changes to the caudal cruciate ligament (CdCL) in dogs with cranial cruciate ligament disease. STUDY DESIGN: Arthroscopic video recordings (n = 117) of the stifle with cranial cruciate ligament disease were reviewed. The extent of CdCL tearing was described. Signalment, palpable stifle stability and the presence of a meniscal tear were recorded. Pathology of the synovial joint and the synovium overlying the CdCL were scored at two time points.Two-way interactions were investigated (p < 0.05). Univariate analysis and a Wald test (p < 0.20) were performed. Factors were retained with a Wald test p < 0.05 or if a confounder, then a changing model coefficient >15%. A weighted kappa statistic was used to evaluate intraobserver agreement. RESULTS: Caudal cruciate ligament tearing was identified in 94% of stifles. Longitudinal tearing (76%) was the most common type of damage (45% partial, 31% full thickness). Synovitis was present in all joints and changes to the synovium overlying the CdCL were less frequently identified (67%).Synovitis was associated with the degree to CdCL tearing. Synovitis overlying the CdCL was associated with lower body weight and lower CdCL damage. CONCLUSION: Caudal cruciate ligament damage is common in dogs with cranial cruciate ligament disease and longitudinal tearing was the most common injury identified. Severity of joint pouch synovitis was positively correlated with the degree of CdCL damage and the portion of the CdCL not exposed to the synovium was unaffected. These findings suggest synovitis is likely a contributor to CdCL injury.

Pain Treatment in the Companion Canine Model to Validate Rodent Results and Incentivize the Transition to Human Clinical Trials.

One of the biggest challenges for analgesic drug development is how to decide if a potential analgesic candidate will work in humans. What preclinical data are the most convincing, incentivizing and most predictive of success? Such a predicament is not unique to analgesics, and the pain field has certain advantages over drug development efforts in areas like neuropsychiatry where the etiological origins are either unknown or difficult to ascertain. For pain, the origin of the problem frequently is known, and the causative peripheral tissue insult might be observable. The main conundrum centers around evaluation of translational cell- and rodent-based results. While cell and rodent models are undeniably important first steps for screening, probing mechanism of action, and understanding factors of adsorption, distribution metabolism and excretion, two questions arise from such studies. First, are they reliable indicators of analgesic performance of a candidate drug in human acute and chronic pain? Second, what additional model systems might be capable of increasing translational confidence? We address this second question by assessing, primarily, the companion canine model, which can provide particularly strong predictive information for candidate analgesic agents in humans. This statement is mainly derived from our studies with resiniferatoxin (RTX) a potent TRPV1 agonist but also from protein therapeutics using a conjugate of Substance P and saporin. Our experience, to date, is that rodent models might be very well suited for acute pain translation, but companion canine models, and other large animal studies, can augment initial discovery research using rodent models for neuropathic or chronic pain. The larger animal models also provide strong translational predictive capacity for analgesic performance in humans, better predict dosing parameters for human trials and provide insight into behavior changes (bladder, bowel, mood, etc.) that are not readily assessed in laboratory animals. They are, however, not without problems that can be encountered with any experimental drug treatment or clinical trial. It also is important to recognize that pain treatment is a major veterinary concern and is an intrinsically worthwhile endeavor for animals as well as humans.

Arthroscopic Articular Cartilage Scores of the Canine Stifle Joint with Naturally Occurring Cranial Cruciate Ligament Disease.

OBJECTIVE: This study aimed to evaluate frequency, location and severity of cartilage pathology in dogs with naturally occurring cranial cruciate ligament (CCL) disease. STUDY DESIGN: Stifle arthroscopic video recordings (n = 120) were reviewed. A modified Outerbridge classification system (MOCS) (0-4) was used to score cartilage at 10 locations in the femorotibial (medial and lateral femoral condyles and tibial plateaus) and patellofemoral compartments (proximal, middle and distal locations of the patella and femoral trochlear groove) of the stifle joint. Synovial pathology was scored and the presence of a medial meniscal tear was recorded. A Kruskal-Wallis test was used to evaluate association of location and synovitis with cartilage score; and presence of meniscal tear with cartilage and synovitis scores. Bonferroni correction was utilized and p < 0.05 was considered significant. RESULTS: Cartilage pathology and synovitis were identified in all joints. Overall cartilage severity scores were low (median MOCS 1). The median MOCS of the proximal trochlear groove (2) was significantly higher than all other locations evaluated. Higher synovitis scores were significantly associated with higher cartilage severity scores and a medial meniscal tear had no association with cartilage severity scores or synovitis. CONCLUSION: Arthroscopic articular cartilage lesions are common in dogs with CCL disease at the time of surgical intervention, although the severity of cartilage damage is mild. The proximal trochlear groove of the femur had the most severe cartilage score in the stifle joint.

Long-term pain relief in canine osteoarthritis by a single intra-articular injection of resiniferatoxin, a potent TRPV1 agonist.

The translational potential of analgesic approaches emerging from basic research can be augmented by client-owned dog trials. We report on a peripheral interventional approach that uses intra-articular injection of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) to produce a selective long-term chemoinactivation of nociceptive primary afferent nerve endings for pain control in naturally occurring canine osteoarthritis. A single injection of 10 µg of RTX, produced suppression of pain, improvement in gait, weight bearing, and improvement in the dog's activities of daily living lasting 4 months or longer. Two to 3 years after the injection, there are no alterations to suggest that removal of inflammatory pain caused accelerated joint degeneration (Charcot joint) in any of the dogs. To amplify the effective use of canine subjects in translational analgesia research, we report a high-quality canine dorsal root ganglion transcriptome. Some targets for analgesia are highly conserved both in protein sequence and level of expression within a target tissue while others diverge substantially from the human. This knowledge is especially important for development of analgesics aimed at peripheral molecular targets and provides a template for informed translational research. The peripheral site of action, long duration of analgesia, apparent safety, and retention of coordination, all resulting from a single dose suggest that intra-articular RTX may be an effective intervention for osteoarthritis pain with few or no side effects and lead to an improved quality of life.

Development and psychometric testing of the Canine Owner-Reported Quality of Life questionnaire, an instrument designed to measure quality of life in dogs with cancer.

OBJECTIVE To describe development and initial psychometric testing of an owner-reported questionnaire designed to standardize measurement of general quality of life (QOL) in dogs with cancer. DESIGN Key-informant interviews, questionnaire development, and field trial. SAMPLE Owners of 25 dogs with cancer for item development and pretesting and owners of 90 dogs with cancer for reliability and validity testing. PROCEDURES Standard methods for development and testing of questionnaire instruments intended to measure subjective states were used. Items were generated, selected, scaled, and pretested for content, meaning, and readability. Response items were evaluated with exploratory factor analysis and by assessing internal consistency (Cronbach α) and convergence with global QOL as determined with a visual analog scale. Preliminary tests of stability and responsiveness were performed. RESULTS The final questionnaire-which was named the Canine Owner-Reported Quality of Life (CORQ) questionnaire-contained 17 items related to observable behaviors commonly used by owners to evaluate QOL in their dogs. Several items pertaining to physical symptoms performed poorly and were omitted. The 17 items were assigned to 4 factors-vitality, companionship, pain, and mobility-on the basis of the items they contained. The CORQ questionnaire and its factors had high internal consistency (Cronbach α = 0.68 to 0.90) and moderate to strong correlations (r = 0.49 to 0.71) with global QOL as measured on a visual analog scale. Preliminary testing indicated good test-retest reliability and responsiveness to improvements in overall QOL. CONCLUSIONS AND CLINICAL RELEVANCE The CORQ questionnaire was a valid, reliable owner-reported questionnaire that measured general QOL in dogs with cancer and showed promise as a clinical trial outcome measure for quantifying changes in individual dog QOL occurring in response to cancer treatment and progression.

Psychometric properties of the Canine Symptom Assessment Scale, a multidimensional owner-reported questionnaire instrument for assessment of physical symptoms in dogs with solid tumors.

OBJECTIVE To describe development and initial psychometric testing of the Canine Symptom Assessment Scale (CSAS), a multidimensional owner-reported questionnaire instrument, in a population of dogs with solid tumors enrolled in clinical trials. DESIGN Questionnaire development and validation study. ANIMALS 238 client-owned dogs with solid tumors. PROCEDURES A 14-symptom questionnaire was developed. Symptoms were defined as subjective physical disturbances dogs experienced during the course of daily living as assessed through proxy reports of pet owners. For each symptom, owners reported frequency and severity of the symptom and extent of distress caused by the symptom for the dog and the owner. Questionnaire content, symptom prevalence and dimensionality, internal consistency, and factor structure were examined. Construct and criterion validity were examined via comparison with the Canine Brief Pain Inventory (CBPI). RESULTS Symptom prevalence was high, with pain and lack of energy reported in most dogs. Severity, versus frequency, was most highly correlated with both dog and owner distress. Two symptoms were removed from consideration because of poor performance. Analysis of the remaining 12 symptoms revealed that they could be grouped into 3 factors: malaise, anxiety, and digestive upset. The CSAS factor and total scores demonstrated predictable relationships with quality of life and pain scores as measured by the CBPI, including a significant association between increasing symptom burden and decreasing quality of life. The Cronbach α for the CSAS was 0.77. CONCLUSIONS AND CLINICAL RELEVANCE The 12-item CSAS was a psychometrically sound owner-reported instrument for assessment of symptom frequency and characteristics in client-owned dogs with solid tumors. Potential applications include clinical research and practice settings.

The learning curve for veterinary surgery residents performing hemilaminectomy surgeries in dogs.

OBJECTIVE To describe the learning curve for veterinary surgery residents performing hemilaminectomy surgeries in dogs. DESIGN Retrospective case review and learning curve evaluation. SAMPLE 13 individuals who completed a 3-year surgery residency program at a university teaching hospital and who had no prior experience performing hemilaminectomies. PROCEDURES The 13 residents performed hemilaminectomies on 399 dogs between July 2006 and July 2013. Medical records were reviewed, and operative time was recorded. Data were examined with a linear mixed-effects model to quantify fixed and random effects, a curve-fitting technique to find the best-fit curve, and a segmented 2-phase linear model to describe the domains and learning rates for 2 phases of learning. RESULTS The linear mixed-effects model indicated that increasing patient body weight and increasing surgical complexity (graded on the basis of number and contiguity of hemilaminectomy sites) were associated with longer operative times and that increasing exposure number was associated with shorter operative times. The monoexponential and biexponential parametric curves were of similar quality in modeling the data. The segmented 2-phase linear model showed an early phase of learning during which operative time decreased rapidly and a late phase when operative time decreased more gradually. CONCLUSIONS AND CLINICAL RELEVANCE The learning curve for the residents suggested that for early exposures, instruction in the form of direct supervision provided substantial benefit. By the tenth exposure, the benefit of instruction diminished and ongoing improvement was primarily a result of refinement. If validated by further study, this understanding of a 2-phase learning curve may inform the design of training programs in veterinary surgery.

Resiniferatoxin: The Evolution of the "Molecular Scalpel" for Chronic Pain Relief.

Control of chronic pain is frequently inadequate or can be associated with debilitating side effects. Ablation of certain nociceptive neurons, while retaining all other sensory modalities and motor function, represents a new therapeutic approach to controlling severe pain while avoiding off-target side effects. transient receptor potential cation channel subfamily V member 1 (TRPV1) is a calcium permeable nonselective cation channel expressed on the peripheral and central terminals of small-diameter sensory neurons. Highly selective chemoablation of TRPV1-containing peripheral nerve endings, or the entire TRPV1-expressing neuron itself, can be used to control chronic pain. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya or nerve terminals induces calcium cytotoxicity and selective lesioning of the TRPV1-expressing nociceptive primary afferent population. This selective neuroablation has been coined "molecular neurosurgery" and has the advantage of sparing motor, proprioceptive, and other somatosensory functions that are so important for coordinated movement, performing activities of daily living, and maintaining quality of life. This review examines the mechanisms and preclinical data underlying the therapeutic use of RTX and examples of such use for the management of chronic pain in clinical veterinary and human pain states.

Factors associated with pathological fractures in dogs with appendicular primary bone neoplasia: 84 cases (2007-2013).

OBJECTIVE: To determine the incidence of pathological fractures associated with appendicular primary bone tumors in dogs managed medically and to identify potential risk factors at the time of radiographic diagnosis that may be associated with eventual pathological fracture. DESIGN: Retrospective case series. ANIMALS: 84 dogs with primary long bone neoplasia treated medically. PROCEDURES: Medical records for dogs with a diagnosis of primary long bone neoplasia based on results of radiography that was confirmed subsequently at necropsy were reviewed. Owners elected medical treatment at a pain clinic. Data regarding clinical signs, diagnostic testing, pathological findings, and outcome were evaluated. RESULTS: 84 dogs met study inclusion criteria with 85 limbs affected. Osteosarcoma was the most common tumor and was identified in 78 of 85 (91.8%) limbs. The median time from diagnosis to euthanasia was 111 days (range, 28 to 447 days). Pathological fractures were identified in 33 of 85 limbs (38%), with the femur most commonly affected, (8/14 [57.1%]), followed by the tibia (9/17 [52.9%]), humerus (10/27 [37%]), radius (5/25 [20%]), and ulna (1/2 [50%]). Logistic regression analysis indicated that tumors arising from long bones other than the radius had odds of eventual fracture 5.05 as great as the odds for tumors of the radius, and lytic tumors had odds of eventual fracture 3.22 as great as the odds for tumors that appeared blastic or mixed lytic-blastic. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that radial primary bone tumors were less likely and lytic tumors were more likely to fracture. The overall incidence of pathological fractures secondary to appendicular primary bone neoplasia in this study with patients treated by means of intensive management for bone pain was higher than previously reported.

The Canine Orthopedic Index. Step 3: Responsiveness testing.

OBJECTIVE: To determine whether the Canine Orthopedic Index (COI) can detect changes in dogs with osteoarthritis (OA) treated with either non-steroidal anti-inflammatory drugs (NSAID) or placebo. STUDY DESIGN: Double blind randomized placebo controlled trial. ANIMALS: Dogs (n = 80) with OA. METHODS: Owners completed the COI on Day 0. Dogs were administered either carprofen or placebo on days 1 through 14. Owners completed the COI again on Day 14. The change in total instrument, stiffness, gait, function, and quality of life scores were assessed between groups. RESULTS: Dogs administered carprofen had significant decreases in the total instrument score (P = .002) as well as 3 of the 4 factor scores compared to dogs treated with placebo (stiffness score P = .015; gait score P = .001; and function score = 0.008). The change in quality of life score was not significantly different between carprofen and placebo treated dogs (P = .124). CONCLUSIONS: The COI delivered the decreases in total instrument, stiffness, gait, and function scores that one would expect in dogs with OA treated with an NSAID compared with placebo administration. In this cohort of dogs, the quality of life score was not sensitive to the changes associated with NSAID administration.

The Canine Orthopedic Index. Step 2: Psychometric testing.

OBJECTIVE: To perform psychometric testing an owner self-administered questionnaire, the Canine Orthopedic Index (COI), designed to assess outcome in dogs with orthopedic disease. STUDY DESIGN: Original study. SAMPLE POPULATION: Owners (n = 20) of dogs with osteoarthritis (OA) for item (question) pretesting, and 80 owners of dogs with OA for reliability and validity testing. METHODS: Standard methodology for the stepwise development and testing of instruments designed to assess subjective states was followed. Items generated in previous studies were pretested for readability, ambiguity, and inter-item correlations; poorly performing items were removed; and the reduced set of items subjected to factor analysis, reliability, and validity testing. RESULTS: Four factors were identified and named on the basis of the items contained in them: "Stiffness," "Gait," "Function," and "Quality of Life." Cronbach's α ranged from 0.76 to 0.86, suggesting the items in each factor could be assessed as a group to compute factor scores (i.e., stiffness, gait, function, and quality of life scores). The test-retest analysis revealed κ values from 0.68 to 0.80. Overall, the scores amongst the 4 factors correlated moderately well (r = 0.52-0.58), with a mild correlation (r = 0.35) between gait and function scores. CONCLUSIONS: The COI is a psychometrically sound owner completed instrument that can assess 4 domains in dogs with OA: Stiffness, Gait, Function, and Quality of Life.

The Canine Orthopedic Index. Step 1: Devising the items.

OBJECTIVE: To develop questions for an owner-completed outcome assessment instrument for dogs with orthopedic disease. STUDY DESIGN: Focus groups, key-informant interviews, surveys. SAMPLE POPULATION: Owners of dogs with osteoarthritis (OA). METHODS: Audio recorded focus groups were transcribed. Descriptive statistics around discussed topics were calculated. A list of frequently discussed behaviors underwent discrimination and frequency endorsement analysis and was circulated for refinement among veterinarians experienced in treating dogs with orthopedic disease. The final list of behaviors was transformed into a series of questions and organized as the preliminary instrument for testing in further studies. RESULTS: Owners (n = 27) participated in 4 focus groups. Based on the frequency of comments generated during focus groups and key-informant interviews, 30 behaviors were further screened by discrimination analysis and endorsement frequency in an additional cohort of 60 owners. No behaviors were classified as "good" for discriminating between front and hind limb disease so a single, non-limb-specific instrument was developed. Four behaviors had an endorsement frequency ≤ 33% and were not considered further for inclusion in the preliminary instrument. Twenty-one questions associated with the remaining behaviors were used to create the preliminary Canine Orthopedic Index (COI) for psychometric testing in further studies. CONCLUSIONS: A 21-question owner-completed COI was successfully developed in preparation for psychometric testing studies.

Articular cartilage lesions of the patellofemoral joint in dogs with naturally occurring cranial cruciate ligament disease.

OBJECTIVE: To evaluate frequency, severity, and location of patellofemoral (PF) osteoarthritis (OA) in dogs with naturally occurring cranial cruciate ligament (CCL) disease. STUDY DESIGN: Cross-sectional observational study. ANIMALS: Dogs (n = 40; stifles, 44). METHODS: Stifle arthroscopic video recordings and radiographs were performed. Cartilage pathology was scored at 3 locations (proximal, middle, distal) in the trochlear groove and patella. A radiographic osteoarthrosis and synovial pathology score were assigned. A Kruskal-Wallis test was used to determine if lesion severity varied by site, synovitis, and osteoarthrosis, and the Dunn's test was used for pairwise comparisons. The variability of body weight was evaluated using 1 way ANOVA; P < .05 was considered significant. RESULTS: Cartilage pathology and synovitis was identified in all PF joints. The proximal aspect of the trochlear groove had significantly higher cartilage scores than the middle and distal sites and the middle groove site was significantly higher than the distal site. The distal aspect of the patella had significantly greater scores than the middle and proximal patellar locations. Higher synovitis scores were associated with increased cartilage scores. Cartilage scores were significantly greater in stifles with higher radiographic osteophytosis, tibial sclerosis, and patellar enthesiophytosis scores. Higher body weights were significantly associated with greater synovial and radiographic scores. CONCLUSIONS: Dogs with CCL disease have a high incidence of PF cartilage pathology and the severity of cartilage lesions varies depending on location within the joint.

Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis.

OBJECTIVE: To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo. ANIMALS: 150 dogs with osteoarthritis. PROCEDURES: Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments. RESULTS: Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3. CONCLUSIONS AND CLINICAL RELEVANCE: The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.

Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain.

BACKGROUND: Substance P-saporin (SP-SAP), a chemical conjugate of substance P and a recombinant version of the ribosome-inactivating protein, saporin, when administered intrathecally, acts as a targeted neurotoxin producing selective destruction of superficial neurokinin-1 receptor-bearing cells in the spinal dorsal horn. The goal of this study was to provide proof-of-concept data that a single intrathecal injection of SP-SAP could safely provide effective pain relief in spontaneous bone cancer pain in companion (pet) dogs. METHODS: In a single-blind, controlled study, 70 companion dogs with bone cancer pain were randomized to standard-of-care analgesic therapy alone (control, n=35) or intrathecal SP-SAP (20-60 µg) in addition to standard-of-care analgesic therapy (n=35). Activity, pain scores, and videography data were collected at baseline, 2 weeks postrandomization, and then monthly until death. RESULTS: Although the efficacy results at the 2-week postrandomization point were equivocal, the outcomes evaluated beyond 2 weeks revealed a positive effect of SP-SAP on chronic pain management. Significantly, more dogs in the control group (74%) required unblinding and adjustment in analgesic protocol or euthanasia within 6 weeks of randomization than dogs that were treated with SP-SAP (24%; P<0.001); and overall, dogs in the control group required unblinding significantly sooner than dogs that had been treated with SP-SAP (P<0.01). CONCLUSION: Intrathecal administration of SP-SAP in dogs with bone cancer produces a time-dependent antinociceptive effect with no evidence of development of deafferentation pain syndrome which can be seen with neurolytic therapies.

Evaluation of coagulation in dogs with partial or complete extrahepatic biliary tract obstruction by means of thromboelastography.

OBJECTIVE: To characterize in vitro coagulation status in a cohort of dogs with extrahepatic biliary tract obstruction (EHBO) and to evaluate these patients for hypercoagulability by means of thromboelastography. DESIGN: Prospective cohort study. Animals-10 dogs with EHBO and 19 healthy control dogs. PROCEDURES: Partial or complete EHBO was confirmed via exploratory celiotomy. Venous blood samples were collected for evaluation of prothrombin time (PT) and activated partial thromboplastin time (APTT); fibrinogen and D-dimer concentrations; protein C and antithrombin activities; and factor VII, VIII, and XI coagulant activities in plasma as well as thromboelastography in whole blood. Thromboelastography variables were measured from the thromboelastography tracing, and a coagulation index was calculated. Thromboelastography results were compared with those of healthy control dogs previously evaluated by the same laboratory. RESULTS: Hypercoagulability was diagnosed in all dogs with EHBO on the basis of a high coagulation index. Thromboelastography variables, including maximal amplitude, α-angle, and coagulation index, were significantly higher, and K (clot formation time) and R (reaction time) were significantly lower in these dogs than in control dogs. All dogs with EHBO had PT and APTT within respective reference ranges. Plasma D-dimer and fibrinogen concentrations were above reference ranges in 8 and 7 dogs, respectively, and protein C and antithrombin activities were below reference ranges in 3 and 1 dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro hypercoagulability was commonly detected in dogs with naturally occurring EHBO. The traditional view of EHBO as a disease that causes hypocoagulability may need to be reconsidered.

Single agent polysaccharopeptide delays metastases and improves survival in naturally occurring hemangiosarcoma.

The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP) is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

An Internet-based survey of risk factors for surgical gastric dilatation-volvulus in dogs.

OBJECTIVE: To evaluate risk factors for gastric dilatation-volvulus (GDV) in a large number of privately owned dogs across a wide geographic area. DESIGN: Internet-based, cross-sectional study. ANIMALS: 2,551 privately owned dogs. PROCEDURES: A questionnaire addressed dog-specific, management, environmental, and personality-associated risk factors for GDV in dogs. Respondents were recruited through the posting of the electronic link to the questionnaire on websites for dog owners; the information was also disseminated at meetings of dog owners and via newsletters, e-mail lists for dog owners and breeders, owner-oriented dog publications, and e-mails forwarded by participants. Descriptive statistics and logistic regression analysis were performed. RESULTS: Factors significantly associated with an increased risk of GDV were being fed dry kibble, anxiety, residence in the United Kingdom, being born in the 1990s, being a family pet, and spending at least 5 hours a day with the owner. Factors associated with a decreased risk of GDV were playing with other dogs and running the fence after meals, fish and egg dietary supplements, and spending equal time indoors and outdoors. A significant interaction between sex and neuter status was observed, with sexually intact females having the highest risk for GDV. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with a high risk of GDV, regular moderate daily and postprandial activity appeared to be beneficial. Feeding only commercial dry dog food may not be the best choice for dogs at risk; however, supplements with fish or eggs may reduced this risk. The effect of neuter status on GDV risk requires further characterization.